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  • 301.
    Dugalic, Mija
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lovén, Ellen
    Umeå University, Faculty of Medicine, Department of Odontology.
    Paradoxical reactions to midazolam in dental care2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 302.
    Däröste, Sebastian
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Pairo, Kosai
    Umeå University, Faculty of Medicine, Department of Odontology.
    Subjective and Objective Side-effects during Treatment with Oral Appliances2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Objectively measured changes in dental occlusion after long-term treatment with oral appliances (OAs) for sleep apnea are known to occur. Our hypothesis was that most patients are unaware of these changes, since they continue treatment for many years. This study aim was to evaluate the relationship between objectively measured bite changes and subjective complaints in a group of long-term treated patients. Seventeen consecutive patients were included in this retrospective observational pilot study. The patients responded to two questionnaires about adherence and side-effects. The first questionnaire (q-unspec) included unspecified questions and the second questionnaire (q-spec) comprised specified questions about well-known side-effects using VAS-scales. Measurements were conducted on plaster casts taken before treatment start and at follow-up regarding changes in overjet, overbite, crowding and spacing during the treatment period. A change of ≥ 1 mm in either of these variables was compared with patients’ reports of ≥ 2 on the VAS-scale. Significant objective bite changes were found only in overjet and in overbite. Two patients reported bite changes in the q-unspec, although none of them had any objective change. Nine of the remaining 15 patients had objective bite changes although only one had felt a bite change according to q-spec. There was no correlation between a decrease in overjet or overbite and the patients’ complaints. The results support our hypothesis that patients are generally uninfluenced by changes in dental occlusion. Patients who are treated with OAs should therefore continuously be followed up regarding bite changes, in order to avoid possible future problems.

     

  • 303.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Studies of p63 and p63 related proteins in patients diagnosed with oral lichen planus2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Oral lichen planus (OLP) is a chronic inflammatory disease of the oral mucosa and also one of the more common mucosal conditions mostly affecting middle aged individuals. Even though OLP is well investigated the etiology of this disease is still unknown, even if autoimmunity as a possible etiologic factor has been suggested. WHO classifies OLP as a pre malignant condition but malignant transformation of OLP is a matter of great controversy. The p53 protein is a tumour suppressor with the potential to induce apoptosis or cell cycle arrest of DNA damaged cells. Another member of the p53 family, p63, comprises six different isoforms, and plays a crucial role in the formation of oral mucosa, salivary glands, teeth and skin. p63 has also been suggested to be involved in development of squamous cell carcinoma of the head and neck (SCCHN). β-catenin, E-cadherin and epidermal growth factor receptor (EGFR) are p63 related proteins and abnormalities in their expression are suggested to be involved in development of SCCHN.

    Methods. Using immunohistochemistry and antibodies directed against p53 and those distinguishing between the p63 isoforms we analysed biopsies of OLP, SCCHN and normal oral tissue. We also mapped levels of p63 and p53 isoforms using RT-PCR technique. Furthermore expression of the p63 related proteins β-catenin, E-cadherin and EGFR was studied using immunoblot analysis. In an attempt to investigate autoimmunity as a causative factor of OLP we analysed sera from patients diagnosed with OLP and matched control individuals in order to see if there were autoantibodies directed against the p53 family.

    Results. When mapping p53 and p63 protein status decreased expression of p63 and increased expression of p53 was seen in OLP compared to normal tissue. In accordance with these results, levels of p63 RNA were also lower in OLP lesions compared with normal tissue. Concerning p53 isoforms, the “original” p53 isoform was expressed in all OLP lesions and normal control tissue. Of the other isoforms, p53β and Δ133p53 were expressed in the majority of samples. Our results regarding p63 related proteins showed a generally lower expression of these proteins in OLP lesions compared to normal control tissue. When studying sera from patients with OLP we found circulating autoantibodies against all six p63 and four p73 isoforms in two patients.

    Conclusions. The potential for malignant transformation of OLP is still a subject of discussion and rather controversial. While some of our results regarding status of p53 and p63 both at protein and RNA levels support this theory, other results concerning for example p63 related proteins point in the opposite direction. Based on our studies it is thus not possible to either support nor contradict the statement that OLP is a clear-cut premalignant condition. In our effort to understand the etiology of OLP we were the first to demonstrate autoantibodies against p63 and p73 in what could be a subgroup of OLP patients. OLP could thus be suggested to be not one distinct disease, but based on our data a disease comprising different subgroups.

  • 304.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Coates, Philip J
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Bourdon, Jean-Christophe
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Expression of novel p53 isoforms in oral lichen planus.2007In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 44, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

    Oral lichen planus (OLP) is a chronic inflammatory disease of unknown origin, showing little spontaneous regression. WHO classifies OLP as a premalignant condition, however, the underlying mechanisms initiating development of cancer in OLP lesions are not understood. The p53 tumour suppressor plays an important role in many tumours, and an increased expression of p53 protein has been seen in OLP lesions. Recently it was shown that the human TP53 gene encodes at least nine different isoforms. Another member of the p53 family, p63, comprises six different isoforms and plays a crucial role in the formation of oral mucosa, salivary glands, teeth and skin. It has also been suggested that p63 is involved in development of squamous cell carcinoma of the head and neck (SCCHN). In contrast to p53, a decreased expression of p63 protein has been seen in OLP lesions. In this study, we mapped the expression of five novel p53 isoforms at RNA and protein levels in OLP and matched normal controls. In the same samples we also measured levels of p63 isoforms using quantitative RT-PCR. Results showed p53 to be expressed in all OLP lesions and normal tissues. The p53beta and Delta133p53 isoforms were expressed in the majority of samples whereas the remaining three novel isoforms analysed were expressed in only a few samples. Levels of p63 isoforms were lower in OLP lesions compared with normal tissue, however, changes were not statistically significant.

  • 305.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Pediatric Dentistry.
    Coates, Philip J
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Decreased expression of the p63 related proteins beta-catenin, E-cadherin and EGFR in oral lichen planus2007In: Oral Oncology, ISSN 1368-8375, E-ISSN 1879-0593, Vol. 44, no 7, p. 634-638Article in journal (Refereed)
    Abstract [en]

    Oral lichen planus (OLP) is a chronic inflammatory disease and although classified by WHO as a premalignant condition, the risk for transformation into squamous cell carcinoma of the head and neck (SCCHN) is a matter of great controversy. The p63 gene encodes six different proteins which are required for development of ectodermally derived tissues such as oral mucosa, salivary glands, teeth and skin. p63 is highly expressed in SCCHN whereas decreased expression is seen in OLP. beta-catenin, E-cadherin and epidermal growth factor receptor (EGFR) are p63 related proteins, and abnormalities in their expression suggested they are involved in development of squamous cell carcinoma of the head and neck (SCCHN). In this study we mapped the expression of these p63 related proteins in OLP and matched normal healthy controls. Results showed decreased expression of beta-catenin, E-cadherin and EGFR in the vast majority of OLP samples compared with the normal controls. This is the first comprehensive study mapping expression of several p63- and SCCHN-related proteins in tissue from patients with OLP. Results showed a mixed expression pattern with OLP variably resembling normal as well as tumour tissue. Based on our present and previous data it cannot be judged whether OLP lesions are at an increased risk of malignant development.

  • 306.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Endodontics.
    Lundqvist, L.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Mucosal lichen planus a systemic disease requiring multidisciplinary care2012In: Oral Diseases, ISSN 1354-523X, E-ISSN 1601-0825, Vol. 18, no Special Issue, Suppl. 1, p. 21-21Article in journal (Other academic)
  • 307.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Endodontics. Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics.
    Lundqvist, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Mucosal lichen planus, a systemic disease requiring multidisciplinary care: a cross-sectional clinical review from a multidisciplinary perspective2012In: Journal of Lower Genital Tract Disease, ISSN 1089-2591, E-ISSN 1526-0976, Vol. 16, no 4, p. 377-380Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to emphasize the importance of seeing mucosal lichen planus (LP) as a systemic disease and not an isolated oral or genital disease and to analyze the proportion of thyroid antibodies among patients with multimucosal LP.

    MATERIALS AND METHODS: All patients examined by the authors and diagnosed with mucosal LP within 1 year were consecutively included. Full medical histories were collected with special emphasis on autoimmune and thyroid diseases. Sera were analyzed for thyroid antibodies and underwent serologic test for herpes virus. The control group comprised 83 healthy volunteers matched regarding sex and age.

    RESULTS: Of the patients, 120 were included, 89 (74%) of whom were women and 31 (26%) were men. The vast majority of the patients had multifocal lesions, whereas oral lesions solely were found in 28% of women and 36% of men. Of the patients, 28% had at least 1 additional autoimmune disease. Approximately half of the women were treated with levothyroxine owing to thyroid disease. Antibodies against herpes simplex virus were found in 60% of the patients and 44% of the controls (p < .03).

    CONCLUSIONS: Lichen planus with mucosal involvement should be considered and taken care of as a systemic disease and not as an isolated oral and/or genital lichen. Contradictory to many former reports, most of our patients have a multimucosal disease that emphasizes the need for a multidisciplinary clinic to get optimal care and treatment.

  • 308.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Endodontics.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Bäcklund, Bodil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Coates, Philip J
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    The use of a novel ELISA method for detection of antibodies against p63 in sera from patients diagnosed with oral and/or genital and skin lichen planus.2010In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714Article in journal (Refereed)
    Abstract [en]

    Lichen planus is a chronic inflammatory disease of mucosa and skin affecting approximately 1-2% of the adult population. Autoimmunity has been implicated in the etiology of this disease, and recently we detected antibodies directed against all six p63 isoforms in sera from 2 out of 20 patients diagnosed with oral lichen planus (OLP) using Western blot analysis. Here we have developed an ELISA method for screening sera for presence of autoantibodies directed against p63. Using the same sera as previously analysed, we show that the optical density ratios for sera from the two patients with known autoantibodies was considerably higher compared to mean optical density ratios for all samples as well as controls analysed. Applying this novel ELISA technique for screening of sera from an additional group of 46 patients with oral and/or genital or skin lichen and 43 matched controls, we detected another three patients with autoantibodies against the p63 proteins. These data are discussed together with the observation that all five patients with detectable p63 autoantibodies from our two studies had clinically severe disease symptoms.

  • 309.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    van der Waal, Isaäc
    Department of Oral and Maxillofacial Surgery, Academic Centre for Dentistry Amsterdam .
    Letter to the editor: Reply to H. M. Ögmundsdóttir & W. P. Holbrook by M. Ebrahimi et al.2011In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, no 9, p. 732-Article in journal (Refereed)
  • 310.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Endodontics.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Van Der Waal, Isaäc
    Oral lichen planus and the p53 family: what do we know?2011In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 40, no 4, p. 281-285Article in journal (Refereed)
    Abstract [en]

    J Oral Pathol Med (2010) Oral lichen planus (OLP) is a relatively common chronic disease of the oral mucosa for which the aetiopathogenesis is not fully understood. It mainly affects middle aged and elderly. The finding of autoantibodies against p63, a member of the p53 family, is a strong indication of autoimmunity as a causative or contributing factor. The WHO classified OLP as a potentially malignant disorder, but still there is an ongoing debate in the literature on this subject. The TP53 gene encodes a tumour suppressor protein that is involved in induction of cell-cycle arrest or apoptosis of DNA-damaged cells. The p63 gene encodes six different proteins that are crucial for formation of the oral mucosa and skin. The coordinated stabilization of p53 and decreased expression of p63 seen in OLP cause induction of apoptosis enabling removal of DNA-damaged cells. In view of the complexity of cancerogenesis, no firm statement can at present be made about the relevance of the observed relationship between p53 and p63 and the possible malignant transformation of OLP.

  • 311.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Coates, Philip J
    Sjöström, Björn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation.2006In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 35, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. METHODS: Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. RESULTS: In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. CONCLUSIONS: Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms

  • 312.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral and Maxillofacial Radiology.
    Coates, Philip J
    Wiik, Allan
    Roos, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Detection of antibodies against p63 and p73 isoforms in sera from patients diagnosed with oral lichen planus.2007In: Journal of Oral Pathology & Medicine, ISSN 0904-2512, E-ISSN 1600-0714, Vol. 36, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    Background: Oral lichen planus (OLP) is a chronic inflammatory disease of oral mucosa. Despite numerous publications and intense research, the etiology of OLP is still unknown, however, autoimmunity as a possible causative factor has been discussed. Methods: In the present study sera from 20 patients clinically and histologically diagnosed with OLP were analyzed for antibodies directed toward p53, p63, and p73 using Western blot. Results: Sera from two patients reacted with all six p63 isoforms, and one also with p73. The strongest reaction was noted against the TAp63beta protein, which is the most potent transactivator of all p63 proteins and is implicated in the differentiation of stratified epithelia. Conclusions: This is the first demonstration of antibodies directed against all p63 and some p73 isoforms in sera from patients diagnosed with OLP.

  • 313. Ehret, Georg B.
    et al.
    Ferreira, Teresa
    Chasman, Daniel I.
    Jackson, Anne U.
    Schmidt, Ellen M.
    Johnson, Toby
    Thorleifsson, Gudmar
    Luan, Jian'an
    Donnelly, Louise A.
    Kanoni, Stavroula
    Petersen, Ann -Kristin
    Pihurl, Vasyl
    Strawbridge, Rona J.
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Hughes, Maria F.
    Meirelles, Osorio
    Kaakinen, Marika
    Bouatia-Naji, Nabila
    Kristiansson, Kati
    Shah, Sonia
    Kleber, Marcus E.
    Guo, Xiuqing
    Lyytikainen, Leo-Pekka
    Fava, Cristiano
    Eriksson, Nidas
    Nolte, Ilja M.
    Magnusson, Patrik K.
    Salfati, Elias L.
    Rallidis, Loukianos S.
    Theusch, Elizabeth
    Smith, Andrew J. P.
    Folkersen, Lasse
    Witkowska, Kate
    Pers, Tune H.
    Joehanes, Roby
    Kim, Stuart K.
    Lataniotis, Lazaros
    Jansen, Rick
    Johnson, Andrew D.
    Warren, Helen
    Kim, Young Jin
    Zhao, Wei
    Wu, Ying
    Tayo, Bamidele O.
    Bochud, Murielle
    Absher, Devin
    Adair, Linda S.
    Amin, Najaf
    Arkingl, Dan E.
    Axelsson, Tomas
    Baldassarre, Damian
    Balkau, Beverley
    Bandinelli, Stefania
    Barnes, Michael R.
    Barroso, Ines
    Bevan, Stephen
    Bis, Joshua C.
    Bjornsdottir, Gyda
    Boehnke, Michael
    Boerwinkle, Eric
    Bonnycastle, Lori L.
    Boomsma, Dorret I.
    Bornstein, Stefan R.
    Brown, Morris J.
    Burnier, Michel
    Cabrera, Claudia P.
    Chambers, John C.
    Chang, I-Shou
    Cheng, Ching-Yu
    Chines, Peter S.
    Chung, Ren-Hua
    Collins, Francis S.
    Connell, John M.
    Doring, Angela
    Dallongeville, Jean
    Danesh, John
    de Faire, Ulf
    Delgado, Graciela
    Dominiczak, Anna F.
    Doney, Alex S. F.
    Drenos, Fotios
    Edkins, Sarah
    Eicher, John D.
    Elosua, Roberto
    Enroth, Stefan
    Erdmann, Jeanette
    Eriksson, Per
    Esko, Tonu
    Evangelou, Evangelos
    Evans, Alun
    Fai, Tove
    Farra, Martin
    Felixl, Janine F.
    Ferrieres, Jean
    Ferrucci, Luigi
    Fornage, Myriam
    Forrester, Terrence
    Franceschinil, Nora
    Franco, Oscar H.
    Franco-Cereceda, Anders
    Fraser, Ross M.
    Ganesh, Santhi K.
    Gao, He
    Gertow, Karl
    Gianfagna, Francesco
    Gigante, Bruna
    Giulianini, Franco
    Goe, Anuj
    Goodall, Alison H.
    Goodarzi, Mark
    Gorski, Mathias
    Grassler, Jurgen
    Groves, Christopher J.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Hartikainen, Anna-Liisa
    Hassinen, Maija
    Havulinna, Aki S.
    Hayward, Caroline
    Hercberg, Serge
    Herzig, Karl-Heinz
    Hicks, Andrew A.
    Hingorani, Aroon D.
    Hirschhorn, Joel N.
    Hofmanl, Albert
    Holmen, Jostein
    Holmen, Oddgeir Lingaas
    Hottenga, Jouke-Jan
    Howard, Phil
    Hsiung, Chao A.
    Hunt, Steven C.
    Ikram, M. Arfan
    Illig, Thomas
    Iribarren, Carlos
    Jensen, Richard A.
    Kahonen, Mika
    Kang, Hyun Min
    Kathiresan, Sekar
    Keating, Brendan J.
    Khaw, Kay-Tee
    Kim, Yun Kyoung
    Kim, Eric
    Kivimaki, Mika
    Klopp, Norman
    Kolovou, Genovefa
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kosova, Gulum
    Krauss, Ronald M.
    Kuh, Diana
    Kutalik, Zoltan
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Lakka, Timo A.
    Lee, Nanette R.
    Lee, I-Te
    Lee, Wen-Jane
    Levy, Daniel
    Li, Xiaohui
    Liang, Kae-Woei
    Lin, Honghuang
    Lin, Li
    Lindstrom, Jaana
    Lobbens, Stephane
    Mannisto, Satu
    Muller, Gabriele
    Muller-Nurasyid, Martina
    Mach, Francois
    Markus, Hugh S.
    Marouli, Eirini
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Menni, Cristina
    Metspalu, Andres
    Mijatovic, Vladan
    Moilanen, Leena
    Montasser, May E.
    Morris, Andrew D.
    Morrison, Alanna C.
    Mulas, Antonella
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nikus, Kjell
    O'Donnell, Christopher J.
    O'Reilly, Paul F.
    Ong, Ken K.
    Paccaud, Fred
    Palmer, Cameron D.
    Parsa, Afshin
    Pedersen, Nancy L.
    Penninx, Brenda W.
    Perola, Markus
    Peters, Annette
    Poulter, Neil
    Pramstaller, Peter P.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rao, Dabeeru C.
    Rasheed, Asif
    Rayner, N. William
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rettig, Rainer
    Rice, Kenneth M.
    Roberts, Robert
    Rose, Lynda M.
    Rossouw, Jacques
    Samani, Nilesh J.
    Sanna, Serena
    Saramies, Jouko
    Schunkert, Heribert
    Sebert, Sylvain
    Sheu, Wayne H-H
    Shin, Young-Ah
    Sim, Xueling
    Smit, Johannes H.
    Smith, Albert V.
    Sosa, Maria X.
    Spector, Tim D.
    Stancakova, Alena
    Stanton, Alice V.
    Stirrups, Kathleen E.
    Stringham, Heather M.
    Sundstrom, Johan
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tai, E-Shyong
    Tanaka, Toshiko
    Tarasov, Kirill V.
    Teumer, Alexander
    Thorsteinsdottir, Unnur
    Tobin, Martin D.
    Tremoli, Elena
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Vaez, Ahmad
    Vaidya, Dhananjay
    van Duijn, Cornelia M.
    van Iperen, Erik P. A.
    Vasan, Ramachandran S.
    Verwoert, Germaine C.
    Virtamo, Jarmo
    Vitart, Veronique
    Voight, Benjamin F.
    Vollenweider, Peter
    Wagner, Aline
    Wain, Louise V.
    Wareham, Nicholas J.
    Watldns, Hugh
    Weder, Alan B.
    Westra, Harm Jan
    Wilks, Rainford
    Wilsgaard, Tom
    Wilson, James F.
    Wong, Tien Y.
    Yang, Tsun-Po
    Yao, Jie
    Yengo, Loic
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Xiaofeng
    Bovet, Pascal
    Cooper, Richard S.
    Mohlke, Karen L.
    Saleheen, Danish
    Lee, Jong-Young
    Elliott, Paul
    Gierman, Hinco J.
    Willer, Cristen J.
    Franke, Lude
    Hovingh, G. Kees
    Taylor, Kent D.
    Dedoussis, George
    Sever, Peter
    Wong, Andrew
    Lind, Lars
    Assimes, Themistocles L.
    Njolstad, Inger
    Schwarz, Peter E. H.
    Langenberg, Claudia
    Snieder, Harold
    Caulfield, Mark J.
    Melander, E.
    Laakso, Markku
    Saltevo, Juha
    Rauramaa, Rainer
    Tuomilehto, Jaakko
    Ingelsson, Erik
    Lehtimaki, Terho
    Hveem, Kristian
    Palmas, Walter
    Marz, Winfried
    Kumar, Meena
    Salomaa, Veikko
    Chen, Yii-Der I.
    Rotter, Jerome I.
    Froguel, Philippe
    Jarvelin, Marjo-Riitta
    Lakatta, Edward G.
    Kuulasmaa, Kari
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
    Hamsten, Anders
    Wichmann, H-Erich
    Palmer, Colin N. A.
    Stefansson, Kari
    Ridker, Paul M.
    Loos, Ruth J. F.
    Chalcravarti, Aravinda
    Deloukas, Panos
    Morris, Andrew P.
    Newton-Cheh, Christopher
    Munroe, Patricia B.
    The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals2016In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 10, p. 1171-1184Article in journal (Refereed)
    Abstract [en]

    To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

  • 314.
    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.

  • 315.
    Ekici, Rifat
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Sundström, Mia
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Thay, Bernard
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Microbiology.
    Lejon, Kristina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Biomedical Laboratory Science.
    Enhanced capture of extramembranous IgM and IgG on B cells in the NOD mouse: implications for immune complex trapping2009In: International Immunology, ISSN 0953-8178, E-ISSN 1460-2377, Vol. 21, no 5, p. 533-541Article in journal (Refereed)
    Abstract [en]

    Binding of various antibody isotypes to B cells through either FcgammaRs or complement receptors has been attributed to play several roles, e.g. in immune complex (IC) transportation and regulation of B cell receptor signaling. We have revealed a novel B cell intrinsic receptor for IgM and IgG which is present in C57BL/6 (B6) mice and is more abundant in non-obese diabetic (NOD) mice. As a consequence, the level of extramembranous IgG monomers and IgM pentamers on peripheral blood B cells from NOD mice was significantly higher compared with B6 mice. The effect of this aberration was that all B cells in peripheral blood of (NOD.IgH(a) x B6(IgH(b)))F(1) mice carried both IgM allotypes on their surface. In addition, analysis of IC binding using IgG- or IgM-opsonized bacterial particles revealed a higher degree of binding in NOD mice compared with B6. We hypothesize that this novel Ig-binding receptor is part of the normal immune system function. The aberrant function in the NOD mouse could contribute to the development of Type 1 diabetes by altering normal B cell functions such as activation, IC transportation and B cell homeostasis.

  • 316.
    Eklöf, Vincy
    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.
    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.
    The reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T polymorphisms and the risk of colorectal cancer: a nested case-referent study2008In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 68, no 5, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Objective. Polymorphisms in genes involved in folate uptake and metabolism may affect folate status and, thereby, the risk of cancer. In this nested case‐referent study, we related two such polymorphisms, reduced folate carrier (RFC1) 80G>A and folate hydrolase 1 (FOLH1) 1561C>T, to the risk of colorectal cancer, taking into account pre‐diagnostic plasma folate and total homocysteine concentrations and the MTHFR 677C>T polymorphism, which were analysed in a previous study.

    Material and methods. Subjects were 220 cases and 414 matched referents from the population‐based Northern Sweden Health and Disease Study.

    Results. The RFC1 80A‐allele was associated with reduced plasma folate and elevated plasma total homocysteine concentrations, but the result was statistically significant only for folate. In contrast, the FOLH1 1561T‐allele was associated with higher plasma folate and reduced plasma total homocysteine concentrations, and the result was statistically significant only for homocysteine. Neither polymorphism was related to the risk of colorectal cancer, either in univariate analysis or after adjusting for body mass index, current smoking, recreational and occupational physical activity and alcohol intake. Further adjustment for folate or homocysteine status or the MTHFR 677C>T polymorphism did not affect risk estimates. Subjects with the RFC1 80AA genotype in combination with low plasma folate concentrations or the MTHFR 677TT genotype had a reduced risk of colorectal cancer of borderline statistical significance.

    Conclusions. These findings suggest that although the RFC1 80G>A and FOLH1 1561C>T polymorphisms may influence folate status, they are not likely to have a major independent role in the development of colorectal cancer.

    Read More: http://informahealthcare.com/doi/abs/10.1080/00365510701805431

  • 317.
    Ekman, Agneta
    Umeå University, Faculty of Medicine, Department of Odontology, Pediatric Dentistry.
    On dental health and related factors in Finnish immigrant children in Sweden1989Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the postwar period Swedish communities have become more multicultural. Although there are about 120,000 Finnish immigrant children below the age of 18 in Sweden, knowledge about their dental health is rather sparse.

    Dental health and related factors were studied in Finnish immigrant children aged 5,8 and 14 years, living in the city of Luleå, northern Sweden. The effect of early dental health education to parents at the Child Health Centres was studied in one age group in Luleå and in one in the municipality of Botkyrka, Stockholm county. All groups of Finnish children were compared to Swedish children matched for age, sex and social class.

    At the age of 5 the prevalence of dental caries was higher than in Swedish control children. At the age of 8, this difference persisted, but was less pronounced in the permanent than in the primary dentition. The net mean caries increment between 5 and 8 years of age was 11.2 in the Finnish group compared to 7.4 in the Swedish. The proportion of children selected for individual prophylaxis and the time used between age 5 and 8 did not differ between the Finnish and the Swedish groups.

    In the Finnish teenagers, the prevalence of dental caries was higher than in the Swedish teenagers. Periodontal health was equally good in all age groups of Finnish and Swedish children. The difference in caries prevalence between the two groups was mainly explained by a more frequent between-meal eating and a higher intake of sucrose-containing products between meals in the Finnish children. Even though they had been included in organized dental care with individual prophylaxis, this was obviously not enough to guarantee them as good a dental health as in the Swedish children.

    Flourides were used to an equal extent in the Finnish and Swedish groups. Toothbrushing was less frequent in all Finnish age groups than in the Swedish controls.

    The Finnish parents were less convinced than the Swedish about their ability to influence the child’s dental health, and more Finnish than Swedish parents also found it necessary to visit a dentist only when they had toothache.

    The Finnish teenagers who had received almost twice as many hours of individual prophylaxis as the Swedish, knew less about the etiology of dental caries but equally much about the etiology of gingivitis.

    The best result of early dental health education to parents, evaluated by comparing prevalence of dental caries of the children at the age of 3, was obtained when information was given three times in Finnish. If information in the mother tongue cannot be offered, an extra session of information in Swedish can also benefit the dental health of the child.

  • 318. Elcock, C
    et al.
    Smith, RN
    Abdellatif, A
    Bäckman, B
    Umeå University, Faculty of Medicine, Odontology.
    Brook, AH
    Simpson, J
    The new enamel defects index: Testing and expansion2006In: European Journal of Oral Science, Vol. 114, no suppl 1, p. 35-38Article in journal (Refereed)
    Abstract [en]

    The Enamel Defects Index (EDI) was created based on three innovative principles: (i) a basic level of the three major categories of defects; (ii) more detailed subcategories of each major category: and (iii) each category scored independently as present ﴾1﴿or absent ﴾0﴿, simplifying decision making. The aim of this investigation was to further test the index in a number of applications and to expand it to record defect subtype and treatment need. Testing was undertaken by operators with different levels of clinical experience. A computer-assisted learning (CAL) package was developed for operator training and calibration. The index was also used on clinical photographs and high-resolution digital images of exfoliated and extracted teeth. Scoring of photographs revealed substantial intra-operator agreement. Training using the CAL package resulted in significant improvement in index use. Intra-operator reproducibility was good to excellent, and interoperator reproducibility was good for buccal surfaces on digital images. Index expansion allowed information on defect subtype, location, and treatment need to be gathered readily. The EDI has high reproducibility and allows more rapid and accurate data collection from clinical and in vitro studies than the Fédération Dentaire Internationale Developmental Defects of Enamel index.

  • 319. Elcock, C
    et al.
    Smith, RN
    Bäckman, Birgitta
    Umeå University, Faculty of Medicine, Odontology.
    Brook, AH
    Simpson, J
    Comparison of methods for measurement of hypoplastic lesions2006In: European Journal of Oral Science, Vol. 114, no suppl 1, p. 365-369Article in journal (Refereed)
    Abstract [en]

    Enamel hypoplasia is a quantitative defect of enamel thickness. Methods previously used for its measurement have limitations in clinical studies. The aim of this study was to investigate new methods of measurement using image analysis. Lesions on 8 teeth affected by enamel hypoplasia were quantified from study models and impression surfaces using an image-analysis system. The measurements made included lesion area and tooth surface area; from these the proportion of tooth surface area affected was calculated. For comparison, manual measurement was performed on impression surfaces and study models, using digital callipers. Images were also acquired of lesions on 12 exfoliated teeth, and the lesion area and total tooth area were calculated. For assessment of intra-operator reliability, the +/-repeatability coefficient was calculated. Measurement of the surface lesions direct from the exfoliated teeth gave the best results overall, followed by direct image analysis of the silicone impression.

  • 320.
    Elofsson, Caroline
    Umeå University, Faculty of Medicine, Department of Odontology.
    The ability of a plug of Coltosol to resist coronal microleakage in endodontically treated teeth. An ex vivo study.2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Materials commonly used in endondontic treatment lack the ability to prevent microleakage into the root canal system. The aim of this study was to evaluate if adding a plug of Coltosol can prevent coronal microleackage in endodontically treated teeth by in vitro dye penetration method.

    In part one in this study 33 single canal human teeth was decoronized, mechanically prepared and obturated with Gutta-percha and AH-plus sealant using the cold lateral condensing technique. Specimens where randomly divided into three groups with 10 specimens in each group. Two teeth served as positive and one as negative control. Group 1 only GP/sealant was used, no plug was placed in the orifice. Specimens in group 2 and 3 where prepared with a 1 mm respectively 3 mm depth coronal cavity and the orifice-cavities was filled with Coltosol. Dye penetration was measured after immersed 30 days.

    In part two, eight teeth was prepared and canals were instrumented and filled in the same procedure as in part one. A 3 mm depth coronal cavity was prepared in four specimens in the remaining four teeth a 3 mm depth apical cavity was prepared. The cavities were filled with Coltosol. Dye penetration was measured after immersed 45 days and 90 days.

    No difference in leakage was observed after immersed in 30 and 45 days. A significant difference in leakage was observed after immersed 90 days (p=0.018), Specimens with a plug of Coltosol showed less dye penetration compared to the ones with only Gutta-percha and sealer.

  • 321.
    Emanuelsson, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Allen, Carl M.
    Rydin, Katarina
    Sjöström, Mats
    Umeå University, Faculty of Medicine, Department of Odontology.
    Osteoblastoma of the temporal articular tubercle misdiagnosed as a temporomandibular joint disorder2017In: International Journal of Oral and Maxillofacial Surgery, ISSN 0901-5027, E-ISSN 1399-0020, Vol. 46, no 5, p. 610-613Article in journal (Refereed)
    Abstract [en]

    This is a case report of a benign osteoblastoma in the temporomandibular joint of a 17-year-old female. The patient had a two-and-a-half-year history of reduced mouth opening accompanied by tenderness and swelling in the left temporomandibular joint (TMJ). Initial treatment included stabilization of occlusion with a splint, jaw exercise and analgesics. At first symptoms decreased, but then increased 18 months later, prompting evaluation by a cone beam computed tomography (CBCT) scan of the joint. The radiographic findings showed a somewhat ill-defined, radiolucent, expansile lesion containing small scattered calcifications. The lesion was removed under general anesthesia and sent for histopathological examination. At 12-month follow-up the patient had normal function in the TMJ without clinical symptoms. CBCT examination showed a small recurrence of 3 millimeter. Another 12 months later CBCT showed a 1 mm increase of the recurrence. Function was normal with a subtle tenderness lateral to the left TMJ. The decision from a multidisciplinary meeting was further annually follow-up. The present case illustrates the importance of radiographic examination of patients with temporomandibular dysfunction when conservative treatment of symptoms does not relieve pain or swelling.

  • 322.
    Eneroth, Elina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Karlsson, Astrid
    Umeå University, Faculty of Medicine, Department of Odontology.
    A role of Aggregatibacter actinomycetemcomitans Outer Membrane Protein 100 in Serum Resistance?2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The disease periodontitis is an inflammatory response to the oral bacterial microflora. The Gram-negative bacterium Aggregatibacter actinomycetemcomitans has been specifically associated with the aggressive type of periodontitis. This species has a number of virulence factors that can contribute to host cell death, tissue inflammation, bone resorption, and colonization advantage relative to other microbes. A. actinomycetemcomitans has defense mechanisms against killing by the complement system (a part of our immune system). In the alternative pathway of complement activation, a protein called Factor H is the main regulator by having the ability to inhibit the complement reactions in three separate ways. Binding of Factor H to the bacterial surface was earlier shown to promote survival in human serum of an A. actinomycetemcomitans serotype d strain. This binding was caused by the outer membrane protein Omp100. The aim of this study was to establish whether Omp100 has a similar role in other serotypes of A. actinomycetemcomitans. For this we examined the serotype a strains D7S and D7SS, and their omp100 knockout mutants, which were generated in this laboratory. Western immunoblotting was used to compare a possible amount difference of the protein in each serotype. By incubating the bacterial strains in human serum, our results showed that lack of Omp100 did not have an obvious negative effect on the serum survival rate in strain D7S nor D7SS. We therefore concluded that omp100 was not required for serum resistance in these serotype a strains, and suggest that there might be another protein or factor in this serotype that is more important for serum resistance.

  • 323.
    Engman, Sara
    Umeå University, Faculty of Medicine, Department of Odontology.
    Expression and Regulation of the Cell Surface Proteins CD47 and SIRPα in Resident Periodontal Cells2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Periodontal disease is an inflammatory disorder affecting the supporting tissues of the tooth. The inflammation triggers a destruction of the connective- and bone tissue surrounding the tooth, a process that is not fully elucidated. It is known that periodontitis shares features with other inflammatory disease like Crohn's disease and rheumatoid arthritis. The cell surface proteins signal regulatory protein alpha (SIRPα) and cluster of differentiation 47 (CD47) are important for the progression of the inflammation in rheumatoid arthritis and Crohn's disease. It has also been shown that lack of SIRPα or CD47 render in reduced number of osteoclast. The aim of this study was to investigate if cells from the periodontium (human gingival fibroblasts) from periodontally healthy individuals express SIRPα and CD47 and if the expression of these membrane proteins is regulated under inflammatory conditions.

     

    We demonstrate, by using quantitative rt-qPCR, that human gingival fibroblasts express both CD47 and SIRPα mRNA. The expression of SIRPα was positively regulated (2-fold) by the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1-beta (IL-1β). TNF-α caused a 2-fold up-regulation of CD47 in human gingival fibroblasts. Neither CD47 nor SIRPα were time-dependently regulated by the two pro-inflammatory cytokines.

     

    We here conclude that SIRPα and CD47 gene expression are up-regulated in human gingival fibroblasts cultured under inflammatory conditions. These findings indicate that SIRPα and CD47 may play a role in periodontal disease. 

  • 324.
    Engström, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Wänman, Anders
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Johansson, Anders
    Keshishian, Patrik
    Forsberg, Mona
    Juvenile Arthritis and Development of Symptoms of Temporomandibular Disorders: A 15-year Prospective Cohort Study2007In: Journal of Orofacial Pain, ISSN 1064-6655, E-ISSN 1945-3396, Vol. 21, no 2, p. 120-126Article in journal (Refereed)
    Abstract [en]

    To compare the development of symptoms of temporomandibular disorders (TMD) in a sample of patients with juvenile arthritis (JA) and a matched control sample.

    Methods: In 1986, 40 patients with JA (28 girls and 12 boys; mean age ± SD, 18 ± 4.5 years) and an ag- and sex-matched control sample were examined for signs and symptoms of TMD. Fifteen years later in 2001, a questionnaire concerning symptoms of TMD was sent to these subjects. Twenty-eight individuals (68%) in the JA sample (20 women and 8 men; mean age ± SD, 35 ± 5.2 years) and 26 controls (19 women and 7 men; 34 ± 4.0 years) were available for the follow-up.

    Results: The overall prevalence of symptoms of TMD increasead between the 2 examinations in both groups. The prevalence of reported TMD symptoms, such as jaw pain, fatigue in the jaws, and difficulty opening the jaws wide, as well as awareness of tooth clenching, headaches, neck and shoulder pains, was significantly greater among the JA sample than among the controls at the follow-up.

    Conclusion: The study indicates that prevalence of pain and dysfunction in the craniofacial or cervical regions of JA patients is increased more than 20 years after the onset of JA compared to healthy individuals.

  • 325.
    Engström, K
    et al.
    Umeå University, Faculty of Medicine, Odontology.
    Petersson, LG
    Twetman, S
    Fluoride concentraition in supragingival dental plaque after a singel intake or habitual consumption of fluoridated milk2002In: Acta odontologica Scandinavica, Vol. 60, no 5, p. 311-314Article in journal (Refereed)
  • 326.
    Engström, Kristina
    Umeå University, Faculty of Medicine, Odontology.
    Fluoride concentration in plaque and saliva and its effects on oral ecology after intake of fluoridated milk2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    According to WHO, the addition of fluoride to milk could be considered as an alternative to water fluoridation for community-based caries prevention in childhood. School-based schemes in developing as well as industrial countries have demonstrated substantial benefits on oral health, but there are limited data available on the local events in the oral cavity after consumption of fluoridated milk. The general aim of the present investigations was to investigate the concentration of fluoride obtained in saliva and dental plaque after ingestion of Fmilk and to explore the possible effects on the oral ecology. A series of controlled studies were performed in vivo in which samples of saliva and dental plaque were collected and analysed with respect to fluoride content, microbial composition and acidogenicity. An in vitro study evaluated the effect on enamel lesion formation. In paper I, significantly increased concentrations of fluoride (p<0.05) were disclosed in saliva 15 minutes after drinking the fluoride-containing water or milk. In the plaque samples however, the F-increase remained significantly elevated still after 2 hours. The availability of fluoride from milk was generally somewhat lower than from water but the differences were not statistically significant in either plaque or saliva. In paper II, the fluoride concentration in plaque was further explored after a single intake or habitual consumption of fluoridated milk together with a regular meal. The results showed that cariesinhibiting levels of fluoride persisted up to 4 hours after intake. There were no significant differences between the single intakes when compared with repeated intakes. In paper III, the influence of fluoridated milk on the salivary microorganisms associated with dental caries was evaluated. No significant alterations of the microflora were found compared with baseline. There was a slight reduction in the proportion of mutans streptococci after 2 and 4 weeks during consumption with fluoridated milk but the difference failed to reach statistical significance. In paper IV it was demonstrated that fluoridated milk significantly (p<0.05) could counteract the lactic acid formation in dental plaque as initiated with sucrose. In paper V, laser fluorescence technique was used to monitor the effect of fluoridated milk on enamel lesion formation in an experimental caries model. The results reinforced previous research and showed a hampering effect of fluoridated milk. No side effects were reported in any of the investigations. The findings of this thesis substantiate that milk is a suitable vehicle for fluoride administration and contribute to the understanding and possible explanations for the anti-caries properties of fluoridated milk. The main conclusions were: a) intake of fluoridated milk resulted in significantly elevated fluoride levels in saliva within the first 15 minutes and up to 4 hours in dental plaque when fluoridate milk was consumed together with meal, b) no significant alteration of the salivary microflora was disclosed after habitual intake of fluoridated milk but a delayed carbohydrate-mediated lactic acid formation in suspensions of dental plaque could be demonstrated, c) the fluoride concentrations in plaque were not negatively influence by the food intake, and d) the in vitro findings advocated that fluoride added to milk reduced enamel lesion formation as assessed by laser fluorescence technique in an experimental caries model.According to WHO, the addition of fluoride to milk could be considered as an alternative to water fluoridation for community-based caries prevention in childhood. School-based schemes in developing as well as industrial countries have demonstrated substantial benefits on oral health, but there are limited data available on the local events in the oral cavity after consumption of fluoridated milk. The general aim of the present investigations was to investigate the concentration of fluoride obtained in saliva and dental plaque after ingestion of Fmilk and to explore the possible effects on the oral ecology. A series of controlled studies were performed in vivo in which samples of saliva and dental plaque were collected and analysed with respect to fluoride content, microbial composition and acidogenicity. An in vitro study evaluated the effect on enamel lesion formation. In paper I, significantly increased concentrations of fluoride (p<0.05) were disclosed in saliva 15 minutes after drinking the fluoride-containing water or milk. In the plaque samples however, the F-increase remained significantly elevated still after 2 hours. The availability of fluoride from milk was generally somewhat lower than from water but the differences were not statistically significant in either plaque or saliva. In paper II, the fluoride concentration in plaque was further explored after a single intake or habitual consumption of fluoridated milk together with a regular meal. The results showed that cariesinhibiting levels of fluoride persisted up to 4 hours after intake. There were no significant differences between the single intakes when compared with repeated intakes. In paper III, the influence of fluoridated milk on the salivary microorganisms associated with dental caries was evaluated. No significant alterations of the microflora were found compared with baseline. There was a slight reduction in the proportion of mutans streptococci after 2 and 4 weeks during consumption with fluoridated milk but the difference failed to reach statistical significance. In paper IV it was demonstrated that fluoridated milk significantly (p<0.05) could counteract the lactic acid formation in dental plaque as initiated with sucrose. In paper V, laser fluorescence technique was used to monitor the effect of fluoridated milk on enamel lesion formation in an experimental caries model. The results reinforced previous research and showed a hampering effect of fluoridated milk. No side effects were reported in any of the investigations.

    The findings of this thesis substantiate that milk is a suitable vehicle for fluoride administration and contribute to the understanding and possible explanations for the anti-caries properties of fluoridated milk. The main conclusions were: a) intake of fluoridated milk resulted in significantly elevated fluoride levels in saliva within the first 15 minutes and up to 4 hours in dental plaque when fluoridate milk was consumed together with meal, b) no significant alteration of the salivary microflora was disclosed after habitual intake of fluoridated milk but a delayed carbohydrate-mediated lactic acid formation in suspensions of dental plaque could be demonstrated, c) the fluoride concentrations in plaque were not negatively influence by the food intake, and d) the in vitro findings advocated that fluoride added to milk reduced enamel lesion formation as assessed by laser fluorescence technique in an experimental caries model.

  • 327.
    Engström, Kristina
    et al.
    Umeå University, Faculty of Medicine, Odontology, Pediatric Dentistry. Pedodonti.
    LG, Pettersson
    Svante, Twetman
    Inhibition of enamel lesion formation by fluoridated milk assessed by laser fluorescence: an in vitro study.2006In: Clinical oral investigations, Vol. 10, no 3, p. 249-252Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the effect of fluoridated milk on enamel lesion formation as assessed by laser fluorescence (LF). The material consisted of 18 extracted premolar teeth that were cut in mesial-distal direction and pairwise assigned to either test or control samples in an experimental caries model. The teeth were exposed to a low-pH 5% cellulose gel for 4 h, 5 days per week immediately followed by a 4-h period in either fluoridated (5 ppm, test) or nonfluoridated milk (control). In the meantime, the specimens were stored in pooled human-stimulated whole saliva in room temperature. All teeth were examined by visual inspection with a magnifying glass and by LF readings (DIAGNOdent) at baseline and after 2 and 4 weeks. The baseline LF readings ranged from 3 to 7 with a mean value of 5.6+/-0.9. The mean values increased with time in both groups but the increase was more marked in the control teeth, 8.7+/-2.3 vs 12.8+/-3.3 after 4 weeks, this difference being statistically significant (p<0.01). The visual examination could not distinguish between the test or control samples after 2 and 4 weeks, respectively. The findings indicated that fluoride added to milk may to some extent counteract enamel lesion formation as assessed by LF in an experimental caries model.

  • 328.
    Engström, Kristina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Petersson, Lars G.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Sjöström, Inger
    Umeå University, Faculty of Medicine, Department of Odontology, Pediatric Dentistry.
    Twetman, Svante
    Umeå University, Faculty of Medicine, Department of Odontology, Pediatric Dentistry.
    Composition of the salivary microflora during habital consumption of fluoridated milk2004In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 62, no 3, p. 143-146Article in journal (Refereed)
    Abstract [en]

    The aim was to evaluate the effect of habitual consumption of fluoridated milk on the composition of the salivary microflora. The study group comprised 20 healthy schoolchildren and young adults with a mean age of 13.6 years and the investigation had a randomized double-blind crossover design with a washout period of 1 month. After professional tooth-cleaning at baseline, the subjects were supplied with either fluoridated (250 mL, 5 ppm F) or non-fluoridated milk for one daily intake during a period of 4 weeks. Salivary samples were collected immediately before tooth-cleaning and after 1, 2, and 4 weeks, respectively. The samples were immediately cultivated for total viable counts, oral streptococci, mutans streptococci, lactobacilli, and actinomyces spp. Bacterial counts were logarithmically transformed before statistical evaluation using ANOVA. No significant alterations of the salivary microflora were found during any of the milk regimens compared with baseline. There was a slight reduction in the proportion of mutans streptococci after 2 and 4 weeks during consumption with fluoridated milk but the difference failed to reach statistical significance. In conclusion, this study was unable to disclose any significant alteration of the composition of the salivary microflora following daily intake of fluoridated milk.

  • 329. Engström, Kristina
    et al.
    Sjöström, Inger
    Umeå University, Faculty of Medicine, Odontology, Pediatric Dentistry. Pedodonti.
    Petersson, Lars G
    Twetman, Svante
    Umeå University, Faculty of Medicine, Odontology, Pediatric Dentistry. Pedodonti.
    Lactic acid formation in supragingival dental plaque after schoolchildren's intake of fluoridated milk.2004In: Oral Health Prev Dent, ISSN 1602-1622, Vol. 2, no 1, p. 13-17Article in journal (Refereed)
    Abstract [en]

    Purpose: Milk can be used as vehicle for fluoride administration. The aim of this study was to investigate the lactic acid formation in dental plaque after daily intake of fluoridated milk. Materials and Methods: The study group consisted of 15 healthy schoolchildren, 6-15 years of age, in a double-blind crossover study design. After a one-week fluoride depletion period, 250 ml of fluoridated standard milk (5ppm; total amount 1.25 mg F) or non-fluoride control milk was consumed once daily together with an ordinary meal during 3 days of plaque accumulation with no oral hygiene. On the fourth day, plaque samples were collected immediately before a final milk intake and then after 30, 60 and 180 minutes. After a washout period of at two weeks, the whole procedure was repeated with the corresponding fluoridated or non-fluoridated milk regimen. All samples were suspended and the sucrose-challenged lactic acid formation rate was determined enzymatically. Results: The results showed a statistically significant (p<0.05) increase of the lactic acid levels 30 min after the intake of the standard (control) milk while no such elevation was evident after the fluoride-containing milk. No differences were found after 60 and 180 min compared with baseline for any of the milks. Conclusion: The findings suggest that fluoride added to milk may counteract the lactic acid formation that follows a non-fluoridated milk intake.

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

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

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

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

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

  • 331.
    Engström-Medén, Karolina
    Umeå University, Faculty of Medicine, Department of Odontology.
    Equine Dentistry: Periodontal Probing of Molariform Teeth2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Periodontitis is a relatively common problem in horses, but still the knowledge of the

    disease’s pathophysiology is very limited. Also the understanding of the healthy state of

    the horse’s periodontal tissues is restricted. The decision-making in the equine (from Latin:

    equinus; of or pertaining to horse) oral care would be facilitated if there was a solid ground

    of evidence based information to rest upon.

    This study aimed to determine the normal range of periodontal probing depth for

    periodontal healthy equine molariform teeth. 42 horses were candidates for the periodontal

    probing. Periodotal measurement (pocket depth: PD) were recorded for the third premolar

    in a quadrant fulfilling the inclusion criteria. Ten measurement points were recorded per

    tooth of buccal and lingual gingiva. PD at the measure points most approximately placed

    were in general the greatest, (mean measurements from 2.8 mm to 3.0 mm). PD at the

    measure points near the buccal or lingual side were more shallow (mean probing depth of

    1.1 mm to 1.3 mm). Presently, there are no specific criteria of the accepted range of

    probing depth in classification of periodontal health or disease in horses. Instead the

    criteria used in small animals were amplified to assumably fit the horse’s size. The findings

    of this study point to a more shallow probing depth in the healthy periodontium of horse

    than earlier presumed. Since there are similarities in the healthy periodontal status of both

    horse and man, and a multidisciplinary collaboration between veterinarians and dentists

    would greatly benefit the future development in equine dentistry.

  • 332. Engvall, Inga-Lill
    et al.
    Svensson, Björn
    Boonen, Annelies
    van der Heijde, Désirée
    Lerner, Ulf H
    Umeå University, Faculty of Medicine, Department of Odontology.
    Hafström, Ingiäld
    Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction2013In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 52, no 4, p. 733-742Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction.

    METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure.

    RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment. CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.

  • 333.
    Ennibi, Oum Keltoum
    et al.
    Department of Periodontology, School of Dentistry, Mohammed V University, Morocco.
    Claesson, Rolf
    Umeå University, Faculty of Medicine, Department of Odontology.
    Akkaoui, Sanae
    Laboratory of Oral Microbiology and Biotechnology, School of Dentistry, Mohammed V University in Rabat, Morocco.
    Reddahi, Sarah
    Department of Periodontology, School of Dentistry, Mohammed V University, Morocco.
    Kwamin, Francis
    Dental School University of Ghana, Ghana.
    Haubek, Dorte
    Section for Pediatric Dentistry, Department of Dentistry and Oral Health, Aarhus University, Denmark.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    High salivary levels of JP2 genotype of Aggregatibacter actinomycetemcomitans is associated with clinical attachment loss in Moroccan adolescents2019In: Clinical and experimental dental research, ISSN 2057-4347, Vol. 5, no 1, p. 44-51Article in journal (Refereed)
    Abstract [en]

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

  • 334.
    Enow, Constance
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Oscarsson, Jan
    Umeå University, Faculty of Medicine, Department of Odontology.
    Mizunoe, Yoshimitsu
    Huang, Shengua
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Meier, Elke
    Benz, Roland
    Sauer-Eriksson, Elisabeth
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Localization and structure of the ClyA protein in Escherichia coli before secretion and pore-formationManuscript (preprint) (Other academic)
  • 335.
    Erfanian, Nima
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ghodbeni, Kaiser
    Umeå University, Faculty of Medicine, Department of Odontology.
    Clinical Description of Patients Diagnosed with Oral and Genital Lichen Planus, a Register Study2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    ABSTRACT

     

    The aim of this study is to chart a cohort of patients in the county of Västerbotten in Sweden who have been diagnosed with lichen planus. In addition to charting, the cohort has also been compared to similar previously studied groups.

     

    The studied group consist of patients who have been referred to the Department of Medical Biosciences and Pathology between years 2009-2015 with suspicious diagnosis of LP.

     

    After exclusion, 214 patients remained of which 130 were diagnosed with Oral LP and 84 with Genital LP. Different data such as age, medications and diseases was extracted from the dental journals.

     

    In this cohort women were more likely to be affected by LP. The mean age for females was 63 years and 53 years for men. In the studied group 17 % were being treated for hypertension, 14 % were treated with 5 or more different medications. Tobacco use was found in 17 % and 12 % were diagnosed with an autoimmune disease.

     

    The results from the studied cohort were in accordance with similar populations in previous studies. There is an undergoing discussion whether OLP and LP are the same disease that affects different sites. 

  • 336.
    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.

  • 337.
    Eriksson, Elsa
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Erlandsson, Emma
    Umeå University, Faculty of Medicine, Department of Odontology.
    Inhibitory Properties of Lactoferrin on Adhesion of Oral Bacteria to Hydroxyapatite2018Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 338. 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.

  • 339.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haworth, Simon
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Allelic Variation in Taste Genes Is Associated with Taste and Diet Preferences and Dental Caries2019In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 11, no 7, article id 1491Article in journal (Refereed)
    Abstract [en]

    Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.

  • 340.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Holgerson, Pernilla Lif
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Saliva and tooth biofilm bacterial microbiota in adolescents in a low caries community2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 5861Article in journal (Refereed)
    Abstract [en]

    The oral cavity harbours a complex microbiome that is linked to dental diseases and serves as a route to other parts of the body. Here, the aims were to characterize the oral microbiota by deep sequencing in a low-caries population with regular dental care since childhood and search for association with caries prevalence and incidence. Saliva and tooth biofilm from 17-year-olds and mock bacteria communities were analysed using 16S rDNA Illumina MiSeq (v3-v4) and PacBio SMRT (v1-v8) sequencing including validity and reliability estimates. Caries was scored at 17 and 19 years of age. Both sequencing platforms revealed that Firmicutes dominated in the saliva, whereas Firmicutes and Actinobacteria abundances were similar in tooth biofilm. Saliva microbiota discriminated caries-affected from caries-free adolescents, with enumeration of Scardovia wiggsiae, Streptococcus mutans, Bifidobacterium longum, Leptotrichia sp. HOT498, and Selenomonas spp. in caries-affected participants. Adolescents with B. longum in saliva had significantly higher 2-year caries increment. PacBio SMRT revealed Corynebacterium matruchotii as the most prevalent species in tooth biofilm. In conclusion, both sequencing methods were reliable and valid for oral samples, and saliva microbiota was associated with cross-sectional caries prevalence, especially S. wiggsiae, S. mutans, and B. longum; the latter also with the 2-year caries incidence.

  • 341.
    Eriksson, Linda
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, School of Dentistry.
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Esberg, Anders
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Microbial complexes and caries in 17-year-olds with and without Streptococcus mutans2018In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 97, no 3, p. 275-282Article in journal (Refereed)
    Abstract [en]

    Streptococcus mutans is a key bacterial species in the caries process, which affects >90% of the population worldwide. However, other acidogenic and aciduric/acidophilic species may contribute to disease development. In Sweden, a country with low prevalences of caries and S. mutans, a significant portion of caries-affected adolescents lack detectable levels of S. mutans. The objectives of the present study were 1) to characterize the tooth biofilm and saliva microbiota of adolescents with caries disease, with or without detectable S. mutans, from tooth biofilm and saliva samples and 2) to assess taxa clustering in the tooth biofilm and saliva samples and relate this information to caries status. For 17-y-old participants ( N = 154), enamel and dentin caries (the total number of present carious surfaces in the enamel and dentin) and caries experience (the number of decayed and filled tooth surfaces) were recorded, dental biofilm and saliva samples obtained, and information on medical and lifestyle habits collected. Multiplex 16S rDNA (V3-V4) sequencing of bacterial DNA was performed with the Illumina MiSeq platform. The Human Oral Microbiome Database and the ProbeSeq pipeline were used in the HOMI NGS procedure. In subjects with caries experience, high levels of S. mutans were associated with a few species and low levels with a panel of saccharolytic species. Present caries was similarly associated with a panel of saccharolytic species in subjects without S. mutans. Furthermore, tooth biofilm microbiota could be used to establish 4 clusters of subjects with different caries experiences. In particular, high levels of S. mutans were associated with the presence of a few influential species in multivariate modeling, including Scardovia wiggsiae. By contrast, a panel of less avid lactic acid-producing species was influential in patients with undetectable or low S. mutans levels in such modeling. These findings support a prominent role of S. mutans in infected adolescents but also the ecologic concept, especially in S. mutans-free subjects.

  • 342.
    Eriksson, P O
    et al.
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Häggman-Henrikson, Birgitta
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Nordh, E
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Clinical Neurophysiology.
    Zafar, H
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Co-ordinated mandibular and head-neck movements during rhythmic jaw activities in man.2000In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 79, no 6, p. 1378-1384Article in journal (Refereed)
    Abstract [en]

    Recent observations in man of concomitant mandibular and head movements during single maximal jaw-opening/-closing tasks suggest a close functional relationship between the mandibular and the head-neck motor systems. This study was aimed at further testing of the hypothesis of a functional integration between the human jaw and neck regions. Spatiotemporal characteristics of mandibular and associated head movements were evaluated for 3 different modes of rhythmic jaw activities: self-paced continuous maximal jaw-opening/-closing movements, paced continuous maximal jaw-opening/-closing movements at 50 cycles/minute, and unilateral chewing. Mandibular and head-neck movements were simultaneously recorded in 12 healthy young adults, by means of a wireless opto-electronic system for 3-D movement recordings, with retro-reflective markers attached to the lower (mandible) and upper (head) incisors. The results showed that rhythmic mandibular movements were paralleled by head movements. An initial change in head position (head extension) was seen at the start of the first jaw-movement cycle, and this adjusted head position was retained during the following cycles. In addition to this prevailing head extension, the maximal jaw-opening/-closing cycles were paralleled by head extension-flexion movements, and in general the start of these head movements preceded the start of the mandibular movements. The results support the idea of a functional relationship between the temporomandibular and the cranio-cervical neuromuscular systems. We therefore suggest a new concept for human jaw function, in which "functional jaw movements" are the result of activation of jaw as well as neck muscles, leading to simultaneous movements in the temporomandibular, atlanto-occipital, and cervical spine joints.

  • 343.
    Eriksson, Per-Olof
    et al.
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Häggman-Henrikson, Birgitta
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Zafar, Hamayun
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Jaw-neck dysfunction in whiplash-associated disorders2007In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 52, no 4, p. 404-408Article in journal (Refereed)
    Abstract [en]

    This paper reports data from recent studies on integrative jaw-neck motor control in healthy subjects and disturbed jaw-neck behaviour in whiplash-associated disorders (WAD). The results show that neck function is an integral part of natural jaw behaviour, and that neck injury can impair jaw function and therefore disturb eating behaviour. We also show preliminary results from implementation of a new approach for rehabilitation of jaw-neck dysfunction and pain in WAD.

  • 344.
    Eriksson, Per-Olof
    et al.
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Zafar, Hamayun
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Musculoskeletal Disordes in the Jaw-Face and Neck2005In: Conn´s Current Therapy: Musculoskeletal Disorders in the Jaw-Face and Neck, Saunders Elsevier , 2005, p. 1128-1133Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    Because different diseases in the jaw-orofacial region may give rise to similar symptoms, proper examination and diagnosis must precede treatment. Musculoskeletal disorders in the jaw-face region, generally termed craniomandbular disorders (CMD), are as prevalent as the two major dental diseases, caries and periodontitis, and constitute a signifiant health problem. There is a strong female preponderance among patients seeking care for CMD, and symptoms and signs are more frequent, severe, and longer-lasting in women than in men. Between 65% and 95% of CMD patients who seek care for the first time are reported to improve. A new concept for natural jaw function suggests that ”functional jaw movements” are the result of jointly activated jaw and neck muscles, leading to simultaneous movements in the temporomandibular, atlanto-occipital, and cervical spine joints, and that these jaw and head-neck movements have neural commands in common, are preprogammed, and are innate. Accordingly, natural jaw function, by definition, includes integrative jaw-neck behavior. A new explanatory model for the development of pain and dysfunction in the jaw-face in subjects with whiplash-associated disorders (WAD) proposes because natural jaw actions require a healthy state of the temporomandibular. atlanto-occipital, and cervical spine joints, it can be assumed that an injury to or disease of any of these three joint systems might derange natural jaw motor control. Based on findings of disturbed jaw-neck function in WAD, a new treatment model is suggested for patients with jaw-face pain and dysfunction and WAD. The rationale behind this approach is that intervention of jaw function by definition includes neck function. Results from implementation of this treatment model, showing improvement of magnitude and speed for both mandibular and head-neck movements, are reported. Finally, an appropriate term for the clinical condition comprising both jaw-face and head-neck pain and dysfunction is cervicocraniomandibular disorders (CCMD).

  • 345.
    Eriksson, Per-Olof
    et al.
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Zafar, Hamayun
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Musculoskeletal disorders in the jaw-face and neck: Temporomandibular Disorders2006In: Conn´s Current Therapy, Saunders Elsevier , 2006, p. 1197-1202Chapter in book (Other (popular science, discussion, etc.))
  • 346.
    Eriksson, Per-Olof
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Zafar, Hamayun
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Rehabilitation Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia ; Rehabilitation Research Chair, King Saud University, Riyadh, Saudi Arabia.
    Backén, Mattias
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Informatics, County Council of Västerbotten, Umeå, Sweden.
    Instant reduction in postural sway during quiet standing by intraoral dental appliance in patients with Whiplash associated Disorders and non-trauma neck pain2019In: Archives of Oral Biology, ISSN 0003-9969, E-ISSN 1879-1506, Vol. 97, p. 109-115Article in journal (Refereed)
    Abstract [en]

    Objectives: This study tested the hypothesis that modulation of jaw sensorimotor control by intraoral dental appliance can reduce postural sway during quiet standing and hence improve standing balance, in patients with whiplash associated disorders (WAD) and non-trauma neck pain. Design: Postural sway during quiet standing with feet together was examined in 54 WAD patients (40 females) and 10 non-trauma patients (8 females) using wireless 3D movement recording technique. Recordings were performed alternating without and with intraoral dental appliance, and with closed eyes and open eyes, respectively. In this protocol the participants served as their own controls. A reference group of 30 healthy subjects (17 females) was also recorded. Each recording lasted 120 s, followed by 3-5 min of rest. Speed, acceleration and perimeter of postural sway area were documented. Results: In the patients, but not in the healthy group, the intraoral dental appliance instantly and significantly reduced standing postural sway in recordings with closed and open eyes. Conclusions: The prompt reduction in standing postural sway from intervention by intraoral dental appliance i.e. improved standing balance, suggests a potent effect on the postural control system by modulation of the jaw sensorimotor system, probably involving reflex transmission. The result opens for new insight into mechanisms behind postural control and the pathophysiology of balance disorders, and adds to the knowledge on plasticity of the nervous system. It may help developing new procedures for assessment and management of impaired balance in WAD and non-trauma neck pain patients.

  • 347.
    Eriksson, Per-Olof
    et al.
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Zafar, Hamayun
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Häggman-Henrikson, Birgitta
    Umeå University, Faculty of Medicine, Odontology, Clinical Oral Physiology.
    Deranged jaw-neck motor control in whiplash-associated disorders2004In: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 112, no 1, p. 25-32Article in journal (Refereed)
    Abstract [en]

    Recent findings of simultaneous and well coordinated head-neck movements during single as well as rhythmic jaw opening-closing tasks has led to the conclusion that functional jaw movements´are the result of activation of jaw as well as neck muscles, leading to simultaneous movements in the temporomandibular, atlanto-occipital and cervical spine joints. It can therefore be assumed that disease or injury to any of these joint systems would disturb natural jaw function. To test this hypothesis, amplitudes, temporal coordination, and spatiotemporal consistency of concomitant mandibular and head-neck movements during single maximal jaw opening-closing tasks were analysed in 25 individuals suffering from whiplash-associated disorders (WAD) using optoelectronic movement recording technique. In addition, the relative durations for which the head position was equal to, leading ahead of, or lagging behind the mandibular position during the entire jaw opening-closing cycle were determined. Compared with healthy individuals, the WAD group showed smaller amplitudes, and changed temporal coordination between mandibular and head-neck movements. No divergence from healthy individuals was found for the spatiotemporal consistency or for the analysis during the entire jaw opening-closing cycle. These findings in the WAD group of a ´faulty, but yet consistent, jaw-neck behaviour may reflect a basic importance of linked control of the jaw and neck sensory-motor systems. In conclusion, the present results suggest that neck injury is associated with deranged control of mandibular and head-neck movements during jaw opening-closing tasks, and therefore might compromise natural jaw function.

  • 348.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Haworth, Simon
    Brunius, Carl
    Lif Holgerson, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 452Article in journal (Refereed)
    Abstract [en]

    Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.

  • 349.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Isehed, Catrine
    Umeå University, Faculty of Medicine, Department of Odontology. Department of Periodontology, Public Dental Health County Council of Gävleborg, Gävle County Hospital, Gävle, Sweden; Center for Clinical Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden.
    Holmlund, Anders
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    Peri-implant crevicular fluid proteome before and after adjunctive enamel matrix derivative treatment of peri-implantitis2019In: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 46, no 6, p. 669-677Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore which peri‐implant crevicular fluid (PICF) protein pattern is associated with the active peri‐implantitis process.

    Materials and methods: Peri‐implant crevicular fluid from 25 peri‐implantitis sites were subjected to proteomic analysis using liquid chromatography–tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between PICF protein pattern and implant loss, bleeding on probing, pocket depth and enamel matrix derivative (EMD) treatment.

    Results: Clustering of subjects based on their 3–12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 differentiated from cluster 3 by 52 proteins (R2 = 90%, Q2 = 80%) and belonging to cluster 2 was associated with implant loss (p = 0.009) and bleeding on probing (p = 0.001). Cluster 3 was associated with implant survival and EMD treatment (p = 0.044).

    Conclusion: Here, we demonstrate that a specific PICF proteomic profile associates with active peri‐implantitis process and implant loss.

  • 350.
    Esberg, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Isehed, Catrine
    Umeå University, Faculty of Medicine, Department of Odontology. Folktandvården Gävleborg AB, Region Gävleborg.
    Holmlund, Anders
    Folktandvården Gävleborg AB, Region Gävleborg.
    Lundberg, Pernilla
    Umeå University, Faculty of Medicine, Department of Odontology.
    PICF proteome before and after adjunctive EMD treatment of peri-implantitisManuscript (preprint) (Other academic)
    Abstract [en]

    Aim: The aim of this study was to explore which peri-implant crevicular fluid (PICF) protein patter that are associated with the active peri-implantitis process.

    Materials and methods: PICF from 25 peri-implantitis sites were subjected to proteomic analysis using liquid chromatography-tandem mass spectrometry before and at 3, 6 and 12 months after treatment, to identify associations between protein expression and implant loss, radiographic bone level change, bleeding on probing, pocket depth, and enamel matrix derivative (EMD) treatment. 

    Results: Clustering of subjects based on their 3 to 12 months PICF proteomic profiles by principal component analysis defined two major clusters. Cluster 2 was differentiated from cluster 3 by 52 proteins (R2=90%, Q2=80%) and belonging to cluster 2 had an odds ratio for implant loss of 7.9 (95% confidence interval 1.8 to 35.9). Cluster 3 was related to implant survival (p=0.007) after 5 years and associated with EMD treatment (p=0.044). Furthermore, cluster 2 was associated with radiographic bone loss (p<0.0001) and bleeding on probing (p=0.001). 

    Conclusion: EMD treatment was associated with the PICF proteomic profile related to implant survival. EMD reduced number of proteins, dominated by proteins associated with implant loss. However, whether these effects are direct or indirect requires further exploration.

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