2021/10/26 更新

写真a

コバヤシ テツオ
小林 哲夫
KOBAYASHI Tetsuo
所属
医歯学総合病院 歯科総合診療科 准教授
職名
准教授
外部リンク

代表的な業績

    • 【論文】 Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis  2015年8月

    • 【論文】 Genetic Risk Factors for Periodontitis in a Japanese Population  2009年12月

    • 【論文】 Effective in vitro clearance of Porphyromonas gingivalis by Fcα receptor I (CD89) on gingival crevicular neutrophils  2001年5月

学位

  • 博士(歯学) ( 1995年3月   新潟大学 )

研究キーワード

  • 遺伝子多型

  • 歯周炎

  • 歯周病

  • 歯周治療

  • 関節リウマチ

研究分野

  • ライフサイエンス / 保存治療系歯学  / 歯周病学・歯周治療学

経歴(researchmap)

  • 新潟大学   医歯学総合病院   准教授

    2007年4月 - 現在

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  • 新潟大学   医歯学総合病院   助教授

    2004年12月 - 2007年3月

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  • 新潟大学   医歯学総合病院   講師

    2003年10月 - 2004年11月

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  • 新潟大学   歯学部附属病院   講師

    2001年11月 - 2003年9月

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  • 新潟大学   歯学部附属病院   助手

    2001年4月 - 2001年10月

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  • 新潟大学   歯学部   助手

    1989年4月 - 2001年3月

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経歴

  • 新潟大学   医歯学総合病院   准教授

    2007年4月 - 現在

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻   准教授

    2007年4月 - 2021年3月

  • 新潟大学   医歯学総合病院   助教授

    2004年12月 - 2007年3月

  • 新潟大学   医歯学総合病院   講師

    2001年11月 - 2004年11月

  • 新潟大学   歯学部附属病院   助手

    2001年1月 - 2001年10月

  • 新潟大学   歯学部   助手

    1989年4月 - 2001年3月

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学歴

  • 新潟大学歯学部

    1981年4月 - 1987年3月

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所属学協会

委員歴

  • 日本歯周病学会   編集委員会委員  

    2021年4月 - 現在   

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    団体区分:学協会

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  • 日本歯周病学会   教育委員会委員  

    2015年4月 - 2021年3月   

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    団体区分:学協会

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  • 日本歯科保存学会   評議員  

    2002年5月 - 現在   

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    団体区分:学協会

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  • 日本歯周病学会   評議員  

    2002年4月 - 現在   

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    団体区分:学協会

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留学歴

  • オランダ王国・ユトレヒト大学医学部免疫学講座   日本学術振興会特定国長期派遣研究員

    1997年4月 - 1997年9月

 

論文

  • Association among periodontitis severity, anti-agalactosyl immunoglobulin G titer, and the disease activity of rheumatoid arthritis 査読

    Chihiro Kaneko, Tetsuo Kobayashi, Satoshi Ito, Noriko Sugita, Akira Murasawa, Hajime Ishikawa, Koichi Tabeta

    Journal of Periodontal Research   2021年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 抗Porphyromonas gingivalis IgG血清抗体価と肝機能マーカー値および肥満との関連性 佐渡コホートにおける横断研究

    高見澤 圭, 杉田 典子, 葭原 明弘, 小林 哲夫, 吉江 弘正, 多部田 康一

    新潟歯学会雑誌   50 ( 2 )   108 - 109   2020年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • Association between serum IgG antibody titers against Porphyromonas gingivalis and liver enzyme levels: A cross-sectional study in Sado Island 査読

    Kei Takamisawa, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kazutoshi Nakamura, Osamu Onodera, Takeshi Momotsu, Naoto Endo, Kenji Sato, Ichiei Narita, Hiromasa Yoshie, Koichi Tabeta

    Heliyon   6 ( 11 )   e05531   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 血中肝機能マーカーと抗Porphyromonas gingivalis抗体価の関連性

    杉田 典子, 高見澤 圭, 葭原 明弘, 小林 哲夫, 吉江 弘正, 多部田 康一

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   152回   148 - 148   2020年6月

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    記述言語:日本語   出版者・発行元:(NPO)日本歯科保存学会  

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  • The periodontal inflamed surface area is associated with the clinical response to biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a retrospective study. 査読 国際誌

    Moe Yamashita, Tetsuo Kobayashi, Satoshi Ito, Chihiro Kaneko, Akira Murasawa, Hajime Ishikawa, Koichi Tabeta

    Modern Rheumatology   30 ( 6 )   990 - 996   2019年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objectives: We evaluated whether the periodontal inflamed surface area (PISA), a measure of the inflammatory burden posed by periodontitis, is associated with the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a retrospective study that collected rheumatologic and periodontal data from 54 patients with RA who had received corticosteroid, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 6 months of bDMARD therapy. After the patients were divided into two groups based on high or low PISA according to the median measurements at baseline, the rheumatologic condition was compared between the groups. Results: The patients with a low PISA showed significantly lower values for the Clinical Disease Activity Index (CDAI) (p = .008), swollen joint count (p = .02), and patient's and evaluator's global assessment (p = .01 and p = .03) and significantly greater decreases in changes in the CDAI from baseline to 6 months than the patients with a high PISA (p = .01), although these values were comparable at baseline. Both univariate and multivariate analyses revealed a significantly positive correlation between the baseline PISA and changes in the CDAI (p = .04 and p < .001). Conclusion: The PISA is associated with the clinical response to bDMARDs in patients with RA.

    DOI: 10.1080/14397595.2019.1680100

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  • 血清抗Porphyromonas gingivalis IgG抗体価と肝機能マーカー値の関連性 新潟県佐渡市における横断研究

    高見澤 圭, 杉田 典子, 葭原 明弘, 小林 哲夫, 吉江 弘正, 多部田 康一

    日本歯周病学会会誌   61 ( 秋季特別 )   130 - 130   2019年10月

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    記述言語:日本語   出版者・発行元:(NPO)日本歯周病学会  

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  • Effects of tofacitinib on the clinical features of periodontitis in patients with rheumatoid arthritis: two case reports 査読

    Tetsuo Kobayashi, Satoshi Ito, Akira Murasawa, Hajime Ishikawa, Hiromasa Yoshie

    BMC Rheumatology   3   13   2019年4月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • The number of remaining teeth as a risk indicator of cognitive impairment: A cross-sectional clinical study in Sado Island. 査読 国際誌

    Ayumi Kuroki, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kazutoshi Nakamura, Takeshi Momotsu, Naoto Endo, Kenji Sato, Ichiei Narita, Hiromasa Yoshie

    Clinical and Experimental Dental Research   4 ( 6 )   291 - 296   2018年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Most studies that have demonstrated an association between number of remaining teeth and cognitive impairment have treated teeth as a continuous variable, although the relationship is nonlinear. The aim of this cross-sectional study was to determine the critical number of remaining teeth in hospital outpatients at which the association with cognitive impairment becomes apparent. Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in Project in Sado for Total Health. In total, 2,530 adults were interviewed and had their teeth counted; 1,476 of these individuals also completed the Mini-Mental State Examination (MMSE) and underwent measurement of their serum high-sensitivity C-reactive protein (hsCRP) levels. Patients on dialysis and those with hsCRP ≥ 10 mg/L were excluded. The final study group consisted of 565 adults (290 men and 275 women) of mean age 69.8 (range 29-91) years. An MMSE score < 24 was considered to indicate cognitive impairment. The subjects were categorized according to whether they had an edentulous jaw or one to 10, 11-20, 21-27, or ≥28 remaining teeth. One hundred twenty-eight of the 565 study participants were diagnosed to have cognitive impairment. Multiple logistic regression analysis revealed associations of cognitive impairment with older age, ischemic heart disease, smoking, and alcohol consumption. After adjustment for covariates, having one to 10 remaining teeth was significantly associated with cognitive impairment. There is a significant association between having only one to 10 remaining teeth and cognitive impairment in hospital outpatients.

    DOI: 10.1002/cre2.147

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  • The KCNQ1 gene polymorphism as a shared genetic risk for rheumatoid arthritis and chronic periodontitis in Japanese adults: A pilot case-control study. 査読

    Tetsuo Kobayashi, Jun-ichi Kido, Yuichi Ishihara, Kazuhiro Omori, Satoshi Ito, Takato Matsuura, Takashi Bando, Jun Wada, Akira Murasawa, Kiyoshi Nakazono, Akio Mitani, Shogo Takashiba, Toshihiko Nagata, Hiromasa Yoshie

    Journal of Periodontology   89 ( 3 )   315 - 324   2018年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/JPER.17-0412

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  • Circulating levels of carbamylated protein and neutrophil extracellular traps are associated with periodontitis severity in patients with rheumatoid arthritis: A pilot case-control study. 査読 国際誌

    Chihiro Kaneko, Tetsuo Kobayashi, Satoshi Ito, Noriko Sugita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie

    PLoS One   13 ( 2 )   e0192365   2018年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: An interrelationship between rheumatoid arthritis (RA) and periodontitis has been suggested due to their common pathogenic mechanisms. Protein carbamylation and neutrophil extracellular traps (NETs) formation have been shown to be related to autoimmune conditions, including RA, but their association with periodontitis has not been elucidated. Therefore, we assessed whether or not circulating levels of carbamylated protein (CarP) and NETs are associated with periodontitis severity and influenced by periodontal treatment. METHODS: We conducted a retrospective case-control study that included 40 patients with RA and periodontitis, 30 patients with periodontitis, and 43 systemically and periodontally healthy controls to assess the circulating levels of CarP and NETs and rheumatologic and periodontal conditions. The same assessments were also performed in 22 patients with RA and periodontitis after 2 months of periodontal treatment, including oral hygiene instruction and full-mouth supragingival scaling. RESULTS: Patients with RA and periodontitis showed significantly higher serum levels of CarP and NETs than the control group (P = 0.04 and P < 0.001, respectively). The serum levels of CarP and NETs were significantly correlated positively with the mean values of probing depth (P = 0.01 and P = 0.007, respectively) and clinical attachment level (P = 0.007 and P = 0.001, respectively) in the 40 patients with RA and periodontitis. Multiple logistic regression analyses also revealed significantly positive associations between the serum levels of CarP and NETs and moderate to severe periodontitis (P = 0.03 and P = 0.001, respectively). Furthermore, periodontal treatment significantly decreased the serum levels of CarP and NETs in patients with RA and periodontitis (P = 0.03 and P = 0.02). CONCLUSION: The circulating levels of CarP and NETs are associated with periodontitis severity and influenced by periodontal treatment in patients with RA.

    DOI: 10.1371/journal.pone.0192365

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  • Association of liver enzyme levels and alveolar bone loss: A cross-sectional clinical study in Sado Island. 査読 国際誌

    Ayumi Kuroki, Noriko Sugita, Shigeki Komatsu, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kazutoshi Nakamura, Takeshi Momotsu, Naoto Endo, Kenji Sato, Ichiei Narita, Hiromasa Yoshie

    Journal of Clinical and Experimental Dentistry   10 ( 2 )   e100-e106   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: The interaction of periodontopathic bacteria with host immune system induces the production of inflammatory mediators which leads to alveolar bone loss (ABL), the essential feature of periodontitis. Concurrently, periodontal diseases cause the elevation of blood cytokine levels, the alteration of gut microbiota and the dissemination of enterobacteria to the liver. Owing to these mechanisms, periodontal disease might be a risk for liver dysfunction. Several epidemiological studies have reported associations between periodontal diseases and liver dysfunction, although the association between ABL and liver dysfunction has not been investigated. This cross-sectional study determined if elevated serum liver enzyme levels were associated with ABL in Japanese adults. Material and Methods: Japanese adults living on Sado Island who visited Sado General Hospital were invited to participate in the study. Participants over 40 years of age who underwent dental panoramic radiography and blood tests were included. Drinking and smoking habits were self-administered. After excluding patients with edentulous jaw, diagnosed liver diseases, and those on dialysis, data from 44 men and 66 women with a mean age of 73 years were analyzed. The average percentage of ABL for each participant was calculated for mesial and distal sites of all remaining teeth. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) were determined. Univariate analyses were performed to select covariates to be put in multivariate analyses. The association between elevated serum liver enzyme levels and the highest quartile of ABL were assessed by multiple logistic regression analysis. Results: After adjusting for covariates, no significant association was found between elevated serum AST, ALT, or GGT levels as dependent variables and the highest quartile of ABL as an explanatory variable. Conclusions: There was no significant association between the elevation of serum liver enzyme levels and ABL in Japanese adults. Key words:Liver enzymes, dental panoramic radiography, alveolar bone loss, Japanese adults.

    DOI: 10.4317/jced.54555

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  • Advanced glycation end-products increase IL-6 and ICAM-1 expression via RAGE, MAPK and NF-κB pathways in human gingival fibroblasts 査読

    Nonaka K, Kajiura Y, Bando M, Sakamoto E, Inagaki Y, Lew JH, Naruishi K, Ikuta T, Yoshida K, Kobayashi T, Yoshie H, Nagata T, Kido J

    Journal of Periodontal Research   53 ( 3 )   334 - 344   2017年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Increased expression of interleukin-6 (IL-6) gene transcript in relation to IL-6 promoter hypomethylation in gingival tissue from patients with chronic periodontitis 査読

    Tetsuo Kobayashi, Kohei Ishida, Hiromasa Yoshie

    Archives of Oral Biology   69   89 - 94   2016年9月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Objective: DNA methylation of the cytokine genes may play a role in the pathogenesis of periodontitis. The aim of this study is to evaluate whether the alteration of interleukin-6 (IL-6) gene promoter methylation in the gingival tissue (GT) and peripheral blood (PB) is unique to chronic periodontitis (CP).
    Design: DNA isolated from the GT and PB of 25 patients with (CP) and 20 healthy controls (H) was modified with sodium bisulfite and analyzed for IL-6 promoter methylation with direct sequencing. The levels of IL-6 mRNA and serum IL-6 protein were evaluated by a quantitative reverse transcription polymerase chain reaction and an enzyme-linked immunosorbent assay.
    Results: The CP group showed that the overall methylation rates of IL-6 promoter that contained 19 cytosine-guanine dinucleotide (CpG) motifs were significantly decreased in GT in comparison to PB (p &lt; 0.001), which was significantly negatively correlated with the probing depth (p = 0.003). The GT and PB of the H group displayed similar overall methylation rates. No significant difference was observed in the methylation rates at each CpG in GT in comparison to the PB in both groups. The levels of IL-6 mRNA in the GT and PB and serum IL-6 of the two groups were comparable. The ratio of IL-6 mRNA in the GT relative to the PB was significantly higher in the CP group than in the H group (p = 0.03).
    Conclusion: The increased expression of IL-6 gene transcription may be related to IL-6 promoter hypomethylation in the GT from CP patients. (C) 2016 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.archoralbio.2016.05.018

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  • Serum Immunoglobulin G Levels to Porphyromonas gingivalis Peptidylarginine Deiminase Affect Clinical Response to Biological Disease-Modifying Antirheumatic Drug in Rheumatoid Arthritis 査読

    Tetsuo Kobayashi, Satoshi Ito, Daisuke Kobayashi, Atsushi Shimada, Ichiei Narita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie

    PLoS One   11 ( 4 )   e0154182   2015年8月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Objectives
    To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA).
    Methods
    In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined.
    Results
    After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. Conclusion
    The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA.

    DOI: 10.1371/journal.pone.0154182

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  • Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis 査読

    A. Kojima, T. Kobayashi, S. Ito, A. Murasawa, K. Nakazono, H. Yoshie

    Journal of Periodontal Research   51 ( 3 )   350 - 358   2015年8月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and ObjectiveOver-expression of tumor necrosis factor-alpha (TNF-) plays a pathological role in chronic periodontitis (CP) and rheumatoid arthritis (RA), which might be regulated by the epigenetic mechanism. The aim of the present study was to evaluate whether there is a unique methylation profile of the TNF- gene promoter in blood cells of individuals with CP and RA.
    Material and MethodsThe study participants consisted of 30 Japanese adults with RA (RA group), 30 race-matched adults with CP only (CP group) and 30 race-matched healthy controls (H group). Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed, by direct sequencing, to investigate DNA methylation of the TNF- gene promoter region. The level of TNF- produced in mononuclear cells stimulated with Porphyromonas gingivalis lipopolysaccharide was determined using ELISA.
    ResultsTwelve cytosine-guanine dinucleotide (CpG) motifs were identified in the TNF- promoter fragment from -343 to +57bp. The CP group showed a significantly higher methylation rate and frequency at -72bp than the H group (p&lt;0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (-302, -163, -119, -72, -49, -38 and +10bp), and significantly higher methylation frequencies at six CpG motifs (-163, -119, -72, -49, -38 and +10bp), than the H group (p&lt;0.01 for all comparisons). The levels of TNF- produced were significantly different between individuals with and without methylation at -163bp (p=0.03).
    ConclusionThese results suggest that the hypermethylated status of CpG motifs in the TNF- gene promoter in blood cells may be unique to Japanese adults with CP and RA.

    DOI: 10.1111/jre.12314

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  • Expression of anti-Porphyromonas gingivalis peptidylarginine deiminase immunoglobulin G and peptidylarginine deiminase-4 in patients with rheumatoid arthritis and periodontitis 査読

    A. Shimada, T. Kobayashi, S. Ito, M. Okada, A. Murasawa, K. Nakazono, H. Yoshie

    Journal of Periodontal Research   51 ( 1 )   103 - 111   2015年6月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and ObjectiveAutoimmunity against citrullinated proteins through peptidylarginine deiminase (PAD) may be involved in the pathophysiology of rheumatoid arthritis (RA). The present study evaluated the serum levels of antibodies to citrullinated proteins and to Porphyromonas gingivalis PAD (PPAD), and the endogenous expression of PAD-4, in individuals with and without RA, as well as before and after periodontal treatment.
    Material and MethodsThe study participants consisted of 52 patients with RA (RA group) and 26 age-, gender- and smoking status-matched healthy controls (non-RA group). Of the 52 patients, 26 were randomly assigned to receive oral hygiene instruction and supragingival scaling (RA subgroup). After periodontal and rheumatologic assessments, the serum levels of anti-cyclic citrullinated peptide (CCP) immunoglobulin G (IgG), anti-PPAD IgG and PAD-4 were determined using ELISA.
    ResultsThe serum levels of anti-CCP IgG and anti-PPAD IgG were significantly higher in the RA group than in the non-RA group (p&lt;0.001 and p=0.03). A significant, positive correlation was observed between the serum levels of anti-PPAD IgG and anti-CCP IgG (p=0.04), but not between the serum levels of PAD-4 and anti-CCP IgG. Multiple logistic regression analyses revealed a significant association between anti-PPAD IgG responses and RA after adjustment for age, gender and smoking (p=0.004). Supragingival scaling significantly improved the periodontal condition and disease activity of RA (p&lt;0.05), but failed to decrease the serum levels of anti-CCP IgG, anti-PPAD IgG and PAD-4 after 2mo of treatment.
    ConclusionThese results might suggest an association between anti-PPAD IgG and anti-CCP IgG responses, implicating a role for PPAD in protein citrullination in patients with RA and periodontitis.

    DOI: 10.1111/jre.12288

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  • Host Responses in the Link Between Periodontitis and Rheumatoid Arthritis. 査読

    Kobayashi T, Yoshie H

    Current Oral Health Reports   2 ( 1 )   1 - 8   2015年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s40496-014-0039-2

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  • Interleukin-6 receptor inhibitor tocilizumab ameliorates periodontal inflammation in patients with rheumatoid arthritis and periodontitis as well as tumor necrosis factor inhibitors 査読

    Tetsuo Kobayashi, Satoshi Ito, Daisuke Kobayashi, Anri Kojima, Atsushi Shimada, Ichiei Narita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie

    Clinical and Experimental Dental Research   1 ( 2 )   63 - 73   2015年

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley-Blackwell  

    Interleukin-6 (IL-6) may play a pathological role in rheumatoid arthritis (RA) and periodontitis. Although the efficacy of medication with IL-6 receptor inhibitor, tocilizumab (TCZ), has been demonstrated in the treatment of RA, very little is known about whether TCZ therapy affects periodontitis. The aim of the present study is to compare periodontal condition in patients with RA and periodontitis before and after TCZ therapy. The study participants consisted of 20 patients with RA and periodontitis who were treated with TCZ and 40 patients with RA and periodontitis who received medication with tumor necrosis factor inhibitor (TNFI). Clinical periodontal and rheumatologic assessments and serum biochemical measurements using enzyme-linked immunosorbent assays were performed at baseline and 3 and 6 months later. TCZ and TNFI therapies significantly reduced periodontal inflammation that was determined by gingival index, bleeding on probing, and probing depth (p &lt
    0.017), although plaque levels were comparable before and after the therapies. Both therapies also significantly decreased disease activity score including 28 joints using C-reactive protein (CRP), number of tender and swollen joints, and serum levels of anti-cyclic citrullinated peptide antibodies, rheumatoid factor, CRP, and matrix metalloproteinase-3 (p &lt
    0.017). Additionally, a significant decrease was observed in periodontal clinical attachment level after TCZ therapy (p &lt
    0.017), but not after TNFI therapy. TCZ therapy significantly decreased serum levels of TNF-α, total immunoglobulin G, and serum amyloid A (p &lt
    0.017), although serum levels of IL-6 and soluble IL-6R were significantly increased (p &lt
    0.017). These results suggest a beneficial effect of TCZ therapy on levels of periodontal inflammation in patients with RA and periodontitis, which might be related to decrease in serum inflammatory mediators.

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  • Periodontal and Serum Protein Profiles in Patients with Rheumatoid Arthritis Treated with Tumor Necrosis Factor Inhibitor Adalimumab 査読

    Tetsuo Kobayashi, Tomoko Yokoyama, Satoshi Ito, Daisuke Kobayashi, Akira Yamagata, Moe Okada, Ken Oofusa, Ichiei Narita, Akira Murasawa, Kiyoshi Nakazono, Hiromasa Yoshie

    Journal of Periodontology   85 ( 11 )   1480 - 1488   2014年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Tumor necrosis factor (TNF)-alpha inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-alpha monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy.
    Methods: The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases.
    Results: The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P &lt; 0.001), and serum levels of TNF-alpha (P &lt; 0.001) and interleukin-6 (P &lt; 0.001) after ADA medication, although plaque levels were comparable. Among a total of 495 protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and alpha-1-acid glycoprotein (P &lt; 0.01).
    Conclusion: These results suggest a beneficial effect of ADA therapy on the periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

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  • Comparative Analysis of Serum Proteins in Relation to Rheumatoid Arthritis and Chronic Periodontitis 査読

    Tomoko Yokoyama, Tetsuo Kobayashi, Satoshi Ito, Akira Yamagata, Kohei Ishida, Moe Okada, Ken Oofusa, Akira Murasawa, Hiromasa Yoshie

    Journal of Periodontology   85 ( 1 )   103 - 112   2014年1月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Rheumatoid arthritis (RA) and chronic periodontitis (CP) are chronic inflammatory conditions and share many pathologic features. The common molecular pathogenesis of the two inflammatory diseases is unclear. The aim of the present study is to evaluate serum protein profiles specific for patients with RA and CP by a comprehensive proteomic analysis.
    Methods: The study participants were: 10 patients with RA, 10 patients with CP, 10 patients with RA and CP, and 10 healthy controls. All groups were balanced for age, sex, and smoking status. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant differences in abundance among the four groups were determined with computer image analysis and identified with mass spectrometry and protein databases.
    Results: A total of 1,694 protein spots were obtained in sera of the four groups. Seven spots were significantly different in abundance among the four groups. Of these, three spots (complement component 3, complement factor H, and ceruloplasmin) were significantly different in the RA+ CP group compared with the other three groups (P &lt; 0.05). The similar profiles of complement component 3, complement factor H, and ceruloplasmin were observed by enzyme-linked immunosorbent assay.
    Conclusion: These results suggest that patients with RA and CP may exhibit three serum proteins with different abundance compared with healthy controls and patients with RA only or CP only.

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  • Assessment of Interleukin-6 Receptor Inhibition Therapy on Periodontal Condition in Patients with Rheumatoid Arthritis and Chronic Periodontitis 査読

    Tetsuo Kobayashi, Moe Okada, Satoshi Ito, Daisuke Kobayashi, Kohei Ishida, Anri Kojima, Ichiei Narita, Akira Murasawa, Hiromasa Yoshie

    Journal of Periodontology   85 ( 1 )   57 - 67   2014年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Overproduction of interleukin (IL)-6 may play a pathologic role in rheumatoid arthritis (RA) and chronic periodontitis (CP). The present study assesses IL-6 receptor (IL-6R) inhibition therapy on the periodontal condition of patients with RA and CP.
    Methods: The study participants were 28 patients with RA and CP during treatment with IL-6R inhibitor, and 27 patients with RA and CP during treatment without IL-6R inhibitor. Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers and immunoglobulin G against periodontopathic bacteria were examined after medication with IL-6R inhibitor for 20.3 months on average (T1) and again 8 weeks later (T2).
    Results: No differences were observed between the groups in any parameter values at T1, except for serum IL-6 levels. The anti-IL-6R group showed a significantly greater decrease in gingival index, bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), and serum levels of IL-6 and matrix metalloproteinase (MMP)-3 from T1 to T2 than the control group (P &lt; 0.05). A significant correlation was found between changes in serum anticyclic citrullinated peptide levels and those in PD and CAL in the anti-IL-6R group (P &lt; 0.05), whereas both groups exhibited a significant association between changes in serum MMP-3 levels and those in BOP (P &lt; 0.05).
    Conclusion: Changes in periodontal and serum parameter values were different between the patients with RA and CP during treatment with and without IL-6R inhibitor.

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  • Periodontal Treatment Decreases Levels of Antibodies to Porphyromonas gingivalis and Citrulline in Patients With Rheumatoid Arthritis and Periodontitis 査読

    Moe Okada, Tetsuo Kobayashi, Satoshi Ito, Tomoko Yokoyama, Asami Abe, Akira Murasawa, Hiromasa Yoshie

    Journal of Periodontology   84 ( 12 )   e74 - e84   2013年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Porphyromonas gingivalis has been implicated as an etiologic agent of rheumatoid arthritis (RA) because of the expression of peptidylarginine deiminase. The present study evaluates whether periodontal treatment may affect serum antibodies to P. gingivalis and citrulline levels in relation to disease activity of RA.
    Methods: Fifty-five patients with RA were randomly assigned to receive oral hygiene instruction and supragingival scaling (treatment group, n = 26) or no periodontal treatment (control group, n = 29). Periodontal and rheumatologic parameters and serum levels of cytokine and inflammatory markers citrulline and immunoglobulin (Ig)G to P. gingivalis were examined at baseline and 8 weeks later.
    Results: Both groups did not differ statistically in any parameters except percentage of sites with probing depth and clinical attachment level &gt;= 4 mm at baseline. The treatment group exhibited a significantly greater decrease in disease activity score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.02), serum levels of IgG to P. gingivalis hemin binding protein (HBP) 35 (P = 0.04), and citrulline (P = 0.02) than the control group. Serum levels of IgG to P. gingivalis HBP35 were significantly correlated positively with those of anti-cyclic citrullinated peptide antibodies (P = 0.0002). The same correlation was obtained between serum levels of IgG to P. gingivalis-sonicated extracts and those of rheumatoid factor (P = 0.02).
    Conclusions: These results suggest that supragingival scaling decreases DAS28-CRP and serum levels of IgG to P. gingivalis HBP35 and citrulline in patients with RA. These observations may reflect a role of P. gingivalis in the protein citrullination, which is related to the pathogenesis of RA.

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  • Interleukin-6 Gene Promoter Methylation in Rheumatoid Arthritis and Chronic Periodontitis 査読

    Kohei Ishida, Tetsuo Kobayashi, Satoshi Ito, Yasutaka Komatsu, Tomoko Yokoyama, Moe Okada, Asami Abe, Akira Murasawa, Hiromasa Yoshie

    Journal of Periodontology   83 ( 7 )   917 - 925   2012年7月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Methylation status of the cytokine genes may play a role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA) and chronic periodontitis (CP). This study was undertaken to evaluate whether the DNA methylation profile of the interleukin-6 (IL-6) gene promoter was unique to individuals with RA and CP.
    Methods: The study participants consisted of 30 patients with RA, 30 patients with CP, and 30 age-, sex-, and smoking status-balanced healthy controls. Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed for DNA methylation levels of IL-6 gene with direct sequencing. Levels of IL-6 were determined by an enzyme-linked immunosorbent assay.
    Results: The region of IL-6 gene promoter from -1200 to +27 bp was shown to contain 19 CpG motifs. The methylation levels of the CpG motif at -74 bp were significantly lower in patients with RA and CP than those in controls (P = 0.0001). Both levels of serum IL-6 and IL-6 production by mononuclear cells were significantly different between individuals with and without the methylation at -74 bp (P = 0.03). The +19 bp motif exhibited differential levels of the methylation among the groups, which was not associated with serum levels of IL-6. The other 17 CpG motifs exhibited comparable levels of the methylation between the groups.
    Conclusion: These results suggest that hypomethylated status of a single CpG in the IL-6 promoter region may lead to increased levels of serum IL-6, implicating a role in the pathogenesis of RA and CP. J Periodontol 2012;83:917-925.

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  • Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis 査読

    Noriko Sugita, Tetsuo Kobayashi, Akira Kikuchi, Yasuko Shimada, Emi Hirano, Jun Sasahara, Kenichi Tanaka, Hiromasa Yoshie

    Journal of Reproductive Immunology   93 ( 2 )   94 - 101   2012年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Many studies have reported an association between periodontal disease and preterm birth, although this remains controversial. Cytokines and antibodies produced to give resistance to infection can enter the bloodstream and cause preterm labor. We analyzed maternal genetic polymorphisms in various immunoregulatory genes that could affect both preterm birth and periodontitis. A total of 1099 women referred to the Department of Obstetrics and Gynecology, Niigata University Medical and Dental Hospital were candidates for participation, 424 of whom refused, and 553 were excluded. The final number of subjects was 122 (51 with preterm birth, 71 with term birth). Genomic DNA was isolated from venous blood, and 22 polymorphisms were determined: IL-1A, IL-1B, IL-1RN, IL-2, IL-4, IL-6, IL-10, TNFA, TNFRI, TNFRII, Fc gamma RIIA, Fc gamma RIIB, Fc gamma RIIIA, Fc gamma RIIIB and Fc alpha R. Within five days of labor, periodontal parameters were evaluated, and bacteria from subgingival plaque were detected using real-time PCR. There was no difference in the prevalence and degree of periodontitis between term and preterm births. Chi-squared tests showed that an age &lt;33 years and Fc alpha R(+56)T/C alleles were associated with preterm birth. Multiple logistic regression analysis represented a model with significant fitness in which four variables were associated with preterm birth: maternal age, number of Aggregatibacter actinomycetemcomitans. IL-6(-572)G/C, and Fc alpha R(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and Fc alpha R were suggested to be associated with preterm birth. Multiple logistic regression models with both genetic and environmental factors would be useful for evaluating susceptibility to preterm birth. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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  • Association of the Fc gamma RIIB-nt645+25A/G polymorphism with the expression level of the Fc gamma RIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis 査読

    N. Sugita, R. Iwanaga, T. Kobayashi, H. Yoshie

    Journal of Periodontal Research   47 ( 1 )   105 - 113   2012年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Sugita N, Iwanaga R, Kobayashi T, Yoshie H. Association of the Fc RIIB-nt645+25A/G polymorphism with the expression level of the Fc RIIb receptor, the antibody response to Porphyromonas gingivalis and the severity of periodontitis. J Periodont Res 2012; 47: 105113. (C) 2011 John Wiley & Sons A/S

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  • Characterization of human-type monoclonal antibodies against reduced form of hemin binding protein 35 from Porphyromonas gingivalis 査読

    Y. Shibata, S. Okano, T. Shiroza, T. Tahara, K. Nakazawa, S. Kataoka, I. Ishida, T. Kobayashi, H. Yoshie, Y. Abiko

    Journal of Periodontal Research   46 ( 6 )   673 - 681   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and Objective: The gram-negative anaerobe Porphyromonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We previously identified a 35 kDa surface protein (hemin binding protein 35; HBP35) from P. gingivalis that exhibited coaggregation activity, while additional analysis suggested that this protein possessed an ability to bind heme molecules. For development of passive immunotherapy for periodontal diseases, human-type monoclonal antibodies have been prepared using HBP35 as an antigen in TransChromo mice. In the present study, we focused on a single antibody, TCmAb-h13, which is known to inhibit heme binding to recombinant HBP35. The aim of our investigation was to clarify the redox-related function of HBP35 and consider the benefits of human-type monoclonal antibodies.
    Material and Methods: To examine the antigen recognition capability of TCmAbs with immunoblotting and Biacore techniques, we used the native form as well as several Cys-to-Ser variants of recombinant HBP35.
    Results: We found that the redox state of recombinant HBP35 was dependent on two Cys residues, (48)C and (51)C, in the thioredoxin active center (WCGxCx). Furthermore, TCmAb-h13 recognized the reduced forms of recombinant HBP35, indicating its inhibitory effect on P. gingivalis growth.
    Conclusion: Hemin binding protein 35 appears to be an important molecule involved in recognition of the redox state of environmental conditions. In addition, TCmAb-h13 had an inhibitory effect on heme binding to recombinant HBP35, thereby interfering with P. gingivalis growth.

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  • Antibody Responses to Periodontopathic Bacteria in Relation to Rheumatoid Arthritis in Japanese Adults 査読

    Moe Okada, Tetsuo Kobayashi, Satoshi Ito, Tomoko Yokoyama, Yasutaka Komatsu, Asami Abe, Akira Murasawa, Hiromasa Yoshie

    Journal of Periodontology   82 ( 10 )   1433 - 1441   2011年10月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Periodontopathic bacteria have been implicated as contributory to the etiology of rheumatoid arthritis (RA). Anticyclic citrullinated peptide (CCP) antibodies and rheumatoid factor (RF) were shown to be associated with RA. This study examines whether serum levels of antibodies to periodontopathic bacteria may affect clinical and laboratory profiles of RA.
    Methods: The study participants consisted of 80 patients with RA, and 38 age-, sex-, smoking status-, and periodontal condition-balanced healthy controls. After periodontal and rheumatologic examination, serum levels of immunoglobulin G(IgG) antibodies to Porphyromonas gingivalis (Pg), Prevotella intermedia, Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), and Eikenella corrodens (Ec) and those of anti-CCP antibodies and RF were determined by an enzyme-linked immunosorbent assay.
    Results: Patients with RA showed significantly higher levels of anti-Pg and anti-CCP antibodies than controls (P = 0.04 and P &lt; 0.0001). In contrast, IgG responses to Aa and Ec in patients with RA were significantly lower than those in controls (P &lt; 0.0001 and P = 0.0001). Multiple logistic regression analysis revealed a significant association of anti-Pg and anti-Aa IgG responses with RA, after adjustment for age, sex, and smoking (P = 0.005 and P = 0.02). Anti-Pg titer displayed a significant correlation with RF levels, probing depth, and clinical attachment level (P = 0.03, P = 0.03, and P = 0.02).
    Conclusion: These results suggest that serum levels of anti-Pg IgG antibodies were associated with RA, and might affect serum levels of RF and periodontal condition in patients with RA. J Periodontol 2011; 82: 1433-1441.

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  • Effects of orally administered lactoferrin and lactoperoxidase-containing tablets on clinical and bacteriological profiles in chronic periodontitis patients 査読

    Tetsuo Kobayashi, Eiju Shimizu, Hiroyuki Wakabayashi, Koji Yamauchi, Keiji Iwatsuki, Hiromasa Yoshie

    International Journal of Dentistry   2011   405139   2011年4月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This study was undertaken to evaluate the effect of oral administration of lactoferrin (LF) and lactoperoxidase-(LPO-)containing tablet on periodontal condition. Seventy-two individuals with chronic periodontitis were randomly assigned to take either bovine LF and LPO-containing tablets (test group, n=37) or control tablets (control group, n=35) every day for 12 weeks. Periodontal parameters and levels of subgingival plaque bacteria, human and bovine LF, and endotoxin in gingival crevicular fluid (GCF) were evaluated at baseline, 1 week, 4 weeks, and 12 weeks. Significant differences were observed in GCF levels of bovine LF between the test and control groups throughout the study (P&lt
    .05). However, clinical and bacteriological parameter values proved comparable between the two groups at 1 week to 12 weeks. Therefore, the effect of oral administration of LF and LPO-containing tablets might be weak on periodontal and bacteriological profile in this study. Copyright © 2011 Eiju Shimizu et al.

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  • Proteomic profiling of human neutrophils in relation to immunoglobulin G Fc receptor IIIb polymorphism 査読

    T. Yokoyama, T. Kobayashi, K. Yamamoto, A. Yamagata, K. Oofusa, H. Yoshie

    Journal of Periodontal Research   45 ( 6 )   780 - 787   2010年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background and Objective:
    Neutrophils are essential in host defense against periodontopathic bacteria. Immunoglobulin G Fc receptor IIIb (Fc gamma RIIIb) is a neutrophil-specific receptor for immunoglobulin G and bears the functional NA1-NA2 polymorphism. Accumulating evidence suggests a significant association between Fc gamma RIIIb gene polymorphism and periodontitis. In this study, we employed a proteomic approach to evaluate the relevance of Fc gamma RIIIb polymorphism to protein expression profiles of neutrophils.
    Material and Methods:ensp;
    Neutrophils were collected from ten healthy subjects whose Fc gamma RIIIb genotypes were determined by allele-specific PCRs. Expressions of proteins induced by interaction via Fc gamma RIIIb were examined between the Fc gamma RIIIb genotypes with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins that were significantly different in expression levels between the Fc gamma RIIIb genotypes were determined with computer image analysis, and identified with mass spectrometry and protein databases.
    Results:
    A total of 757 protein spots were observed in the two-dimensional electrophoretograms of neutrophils from five Fc gamma RIIIb-NA1/NA1 and five Fc gamma RIIIb-NA2/NA2 donors. A statistical analysis revealed that the expression levels of five proteins were significantly different between the Fc gamma RIIIb genotypes (p &lt; 0.05). The Fc gamma RIIIb-NA1/NA1 neutrophils exhibited two spots that were significantly underexpressed (protein-arginine deiminase type-4 and annexin VI) and three spots that were significantly overexpressed (Cdc42hs-Gdp complex, myosin light chain 12A and coactosin-like 1) when compared with Fc gamma RIIIb-NA2/NA2 neutrophils. The same expression profiles of protein-arginine deiminase type-4 were obtained by ELISA.
    Conclusion:
    Differential protein expression profiles were observed in neutrophils between Fc gamma RIIIb genotypes.

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  • Periodontitis, periodontopathic bacteria and lactoferrin 査読

    Hiroyuki Wakabayashi, Ichiro Kondo, Tetsuo Kobayashi, Koji Yamauchi, Tomohiro Toida, Keiji Iwatsuki, Hiromasa Yoshie

    BioMetals   23 ( 3 )   419 - 424   2010年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Lactoferrin (LF) is a component of saliva and is suspected to be a defense factor against oral pathogens including Streptococcus mutans and Candida albicans. Periodontitis is a very common oral disease caused by periodontopathic bacteria. Antimicrobial activities and other biological effects of LF against representative periodontopathic bacteria, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella intermedia, have been widely studied. Association of polymorphisms in LF with incidence of aggressive periodontitis and the role of LF in the gingival crevicular fluid as a marker of periodontitis severity have also been reported. Periodontopathic bacteria reside as a biofilm in supragingival and subgingival plaque. Our recent study indicated that LF exhibits antibacterial activity against planktonic forms of P. gingivalis and P. intermedia at higher concentrations, and furthermore, LF effectively inhibits biofilm formation and reduces the established biofilm of these bacteria at physiological concentrations. A small-scale clinical study indicated that oral administration of bovine LF reduces P. gingivalis and P. intermedia in the subgingival plaque of chronic periodontitis patients. LF seems to be a biofilm inhibitor of periodontopathic bacteria in vitro and in vivo.

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  • Serum Cytokine and Periodontal Profiles in Relation to Disease Activity of Rheumatoid Arthritis in Japanese Adults 査読

    Tetsuo Kobayashi, Akira Murasawa, Yasutaka Komatsu, Tomoko Yokoyama, Kohei Ishida, Asami Abe, Kouji Yamamoto, Hiromasa Yoshie

    Journal of Periodontology   81 ( 5 )   650 - 657   2010年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions and share many pathologic features. A similar profile of cytokines is involved in the pathogenesis of the two diseases. The relationship between the disease activity of RA and the periodontal condition remains unclear. This study examines whether the disease activity of RA affects serum cytokine and periodontal profiles.
    Methods: The study subjects consisted of 84 Japanese adults with RA and 22 race-matched control individuals. After periodontal and rheumatologic examination, the disease activity of RA was determined with the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP). Serum levels of cytokines including interleukin (IL)-1 beta, IL-6, IL-12, IL-12 p40, IL-18, and tumor necrosis factor-alpha (TNF-alpha) were determined by an enzyme-linked immunosorbent assay. High-sensitive CRP was also measured with a latex particle-enhanced nephelometric method.
    Results: Of 84 patients with RA, 28 and 56 patients exhibited low and moderate to high disease activity, respectively. Serum levels of IL-6, TNF-alpha, and CRP were significantly different between the two groups (P&lt;0.05). Additionally, a significant correlation was observed between DAS28-CRP and percentage of sites with bleeding on probing (BOP) (P = 0.008) and between serum TNF-alpha levels and percentage of sites with BOP (P = 0.01) in 56 patients with RA with moderate to high activity.
    Conclusion: These results suggest that the disease activity of RA correlated with serum levels of IL-6, TNF-alpha, and CRP, and it might influence BOP in the patients with moderate to high disease activity. J Periodontol 2010;81:650-657.

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  • Genetic Risk Factors for Periodontitis in a Japanese Population 査読

    T. Kobayashi, T. Nagata, S. Murakami, S. Takashiba, H. Kurihara, Y. Izumi, Y. Numabe, H. Watanabe, M. Kataoka, A. Nagai, J. Hayashi, H. Ohyama, Y. Okamatsu, Y. Inagaki, H. Tai, H. Yoshie

    Journal of Dental Research   88 ( 12 )   1137 - 1141   2009年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SAGE PUBLICATIONS INC  

    Genetic variants at multiple loci have been shown to be associated with susceptibility to periodontitis. To better assess the genetic risk factors for periodontitis, we performed a case-control study in 319 Japanese individuals with periodontitis (172 aggressive and 147 chronic disease) and 303 race-matched healthy control individuals. Thirty-five functional gene polymorphisms that had been previously associated with immune responses were genotyped. For all gene polymorphisms tested, no significant differences were observed in the allele frequencies of persons with aggressive, chronic, and combined ( aggressive and chronic) periodontitis, compared with control individuals. Multiple logistic regression analysis revealed a significant association of the vitamin D receptor + 1056 T/C polymorphism with susceptibility to chronic periodontitis, after adjustment for age, gender, and smoking status (P = 0.002). These results suggest that none of the polymorphisms tested was strongly associated with periodontitis in a Japanese population. However, the vitamin D receptor + 1056 polymorphism may be related to chronic periodontitis.

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  • Assessment of 14 functional gene polymorphisms in Japanese patients with oral lichen planus: a pilot case-control study 査読

    H. Fujita, T. Kobayashi, H. Tai, M. Nagata, H. Hoshina, R. Nishizawa, R. Takagi, H. Yoshie

    International Journal of Oral and Maxillofacial Surgery   38 ( 9 )   978 - 983   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Oral lichen planus (OLP) is a refractory mucosal disease. Its pathogenesis is thought to involve immunologic and genetic alterations. To gain a better understanding of the genetic risk factors, the authors evaluated associations between 14 functional gene polymorphisms and OLP. 32 Japanese patients with OLP and 99 unrelated healthy Japanese controls were genotyped for 14 single nucleotide polymorphisms (SNPs) of genes that regulate host immune responses. Genotyping was performed with a modified version of the serial invasive signal amplification reaction. A trend towards over-representation of tumor necrosis factor receptor 2 (TNFR2) +587 G allele was found in the patients compared with the controls (allele frequency: P = 0.049). The other 13 SNPs were unassociated with OLP. These results suggest that TNFR2 +587 gene polymorphism may be associated with susceptibility to OLP. © 2009 International Association of Oral and Maxillofacial Surgeons.

    DOI: 10.1016/j.ijom.2009.05.001

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  • Inhibitory Effects of Lactoferrin on Growth and Biofilm Formation of Porphyromonas gingivalis and Prevotella intermedia 査読

    Hiroyuki Wakabayashi, Koji Yamauchi, Tetsuo Kobayashi, Tomoko Yaeshima, Keiji Iwatsuki, Hiromasa Yoshie

    Antimicrobial Agents and Chemotherapy   53 ( 8 )   3308 - 3316   2009年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with &gt;= 130 mu g/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and &gt;= 6 mu g/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (&gt;= 8 mu g/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases.

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  • Cytokine Gene Polymorphisms Associated With Rheumatoid Arthritis and Periodontitis in Japanese Adults 査読

    Tetsuo Kobayashi, Akira Murasawa, Satoshi Ito, Kouji Yamamoto, Yasutaka Komatsu, Asami Abe, Takayuki Sumida, Hiromasa Yoshie

    Journal of Periodontology   80 ( 5 )   792 - 799   2009年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Cytokines play a major role in the pathogenesis of rheumatoid arthritis (RA) and periodontitis. Both diseases were previously shown to be partly influenced by cytokine gene polymorphisms. Therefore, we evaluated whether the distributions of the cytokine genotypes were unique to subjects with both diseases.
    Methods: The study subjects consisted of Japanese adults with RA (RA group; n = 153), periodontitis only (P group; n = 117), and healthy individuals (H group; n = 108). Clinical periodontal condition was defined by measurements of probing depth, clinical attachment level, and bleeding on probing. Genomic DNA was isolated from peripheral blood and analyzed for the determination of 16 gene polymorphisms encoding interleukin (IL)-1, -2, -4, -6, and -10, tumor necrosis factor-alpha, and transforming growth factor-beta 1.
    Results: The frequency of patients with RA who exhibited periodontitis was 89.5% (RA + P group; n = 137). No significant differences were observed in any of the frequencies of cytokine genotypes and alleles among the subject groups. After adjustment for age, gender, and smoking status, multiple logistic regression analysis revealed a significant difference in the distribution of IL-IB +3954 genotypes between RA + P and P groups (P=0.006) and between RA + P and H groups (P = 0.008).
    Conclusion: Japanese individuals with RA and periodontitis may exhibit different distributions of IL-IB +3954 genotypes than healthy controls and subjects with periodontitis only. J Periodontol 2009;80:792-799.

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  • Assessment of Chromosome 19 for Genetic Association in Severe Chronic Periodontitis 査読

    Koichi Tabeta, Yasuko Shimada, Hideaki Tai, Yuichi Ishihara, Toshihide Noguchi, Yoshihiko Soga, Shogo Takashiba, Genki Suzuki, Terukazu Kobayashi, Akira Oka, Tetsuo Kobayashi, Kazuhisa Yamazaki, Hidetoshi Inoko, Hirornasa Yoshie

    Journal of Periodontology   80 ( 4 )   663 - 671   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: A genome-association study is a powerful toot for analyzing small gene effects in complex diseases such as chronic periodontitis (CP), although the cost of analysis is prohibitive. We designed a study using the DNA pooling method, which could be a breakthrough in lowering such costs. This study was conducted to assess the genetic association in severe CP in a Japanese population.
    Methods: We adopted a DNA pooling method by genotyping 454 densely spaced microsatellite (MS) markers in chromosome 19 as a pilot study, with the possibility of future use in a whole-genome study. This can reduce the high cost and technical burden, which is generally unavoidable in a genomic association study. Pooled DNA samples from 300 case subjects, 300 control subjects, and 200 systemically healthy subjects were screened by genotyping MS markers. The case-control association in the candidate region was analyzed by individual typing of MS and single nucleotide polymorphisms (SNPs).
    Results: The single MS marker allele 17 of 1902G31 was isolated in association with severe CP (P = 0.0012 for 2 x 2; P&lt;0.046 for 2 x m, where m refers to the number of polymorphic alleles observed in a population). No other SNP or MS polymorphism hypothesized to affect biologic functions in the critical region was found in the linkage disequilibrium block analysis.
    Conclusions: We efficiently isolated the susceptible locus for severe CP in chromosome 19 and identified a useful marker to evaluate the risk for disease. This approach can be applied to a whole-genome study in severe CP. J Periodontol 2009;80:663-671.

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  • Mannose binding lectin gene polymorphism and the severity of chronic periodontitis 査読

    Akito Tsutsumi, Tetsuo Kobayashi, Satoshi Ito, Daisuke Goto, Isao Matsumoto, Hiromasa Yoshie, Takayuki Sumida

    Japanese Journal of Clinical Immunology   32 ( 1 )   48 - 52   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objective: Mannose binding lectin (MBL) is a key molecule in first line defense against variou's microorganisms. Polymorphism of the MBL gene greatly affects serum MBL concentration, and is known to be associated with occurrence of infectious diseases. We aimed to determine whether there is a relationship between occurrence or severity of chronic periodontitis (CP) and polymorphism of the MBL gene. Patients and methods: Ninety-eight CP patients and 63 healthy subjects with no periodontitis were typed for the codon 54 polymorphism of the MBL gene by PCR-restriction fragment length polymorphism method. Results: Genotype frequencies of the codon 54 polymorphism were similar between patients and control subjects. When patients were categorized to mild, moderate and severe periodontits groups, possession of the low serum MBL concentration allele was a risk factor for having severe CP, as assessed by logistic regression analysis. Conclusion: Patients with MBL genotypes that cause lower serum MBL concentration may be at risk of having severe periodontitis. MBL gene typing may become useful to predict the prognosis of CP. © 2009 The Japan Society for Clinical Immunology.

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  • Lower antibody response to Porphyromonas gingivalis associated with immunoglobulin G Fc gamma receptor IIB polymorphism 査読

    Y. Honma, N. Sugita, T. Kobayashi, Y. Abiko, H. Yoshie

    Journal of Periodontal Research   43 ( 6 )   706 - 711   2008年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Human Fc gamma RIIB is one of the receptors for immunoglobulin G (IgG) and suppresses the activation of B lymphocytes through cross-linking with the B cell receptor via immune complexes. This function of Fc gamma RIIB is essential for the negative regulation of antibody production. Our previous study has demonstrated the gene polymorphism Fc gamma RIIB-I232T to be associated with periodontitis. The polymorphism Fc gamma RIIB-232T has been reported to inhibit B-cell antigen receptor signaling more effectively compared to Fc gamma RIIB-232I, while other groups concluded that Fc gamma RIIB-232T had no ability to inhibit activatory receptors. In this study, we examined whether Fc gamma RIIB-I232T polymorphism would change the IgG antibody response to the periodontopathic bacteria Porphyromonas gingivalis.
    Forty-seven patients with periodontitis were genotyped with the direct sequencing of genome DNA. Serum IgG and specific IgG subclass levels for the sonicate of P. gingivalis and the recombinant 40 kDa outer membrane protein (OMP) were determined.
    No significant difference in the total IgG level and IgG response to P. gingivalis sonicate were observed between sera from Fc gamma RIIB-232T carriers and non-carriers. The Fc gamma RIIB-232T carriers revealed a significantly lower IgG(2) response to P. gingivalis 40 kDa OMP compared to non-carriers (p = 0.04, Mann-Whitney U-test). Lower responses of Fc gamma RIIB-232T carriers were also observed in specific IgG and IgG(1) levels. The Fc gamma RIIB-232T carriers revealed a low level of IgG(2) response to P. gingivalis 40 kDa OMP, even with a high average probing pocket depth.
    These results suggest that association of the Fc gamma RIIB-232T allele with periodontitis might be related to the lower levels of antibody response to P. gingivalis.

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  • Association of interleukin-1 receptor antagonist+2018 gene polymorphism with Japanese chronic periodontitis patients using a novel genotyping method 査読

    Y. Komatsu, J. C. Galicia, T. Kobayashi, K. Yamazaki, H. Yoshie

    International Journal of Immunogenetics   35 ( 2 )   165 - 170   2008年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Genetic variants at multiple loci have been shown to be associated with periodontitis risk. In this study, we have focused on nine functional gene polymorphisms encoding immunoregulation-related molecules such as cytokines (interleukin-1 (IL-1), transforming growth factor-beta 1 (TGF-beta 1)) and cell surface receptors (immunoglobulin G and A Fc receptors (Fc gamma R and Fc alpha R)). In total, 113 Japanese patients with chronic periodontitis (CP) and 108 race-matched healthy controls were genotyped with the modified serial invasive signal amplification reaction. There was a significant difference in the distribution of IL-1 receptor antagonist (RN) +2018 T/C allele between the patient and control groups, with enrichment of the +2018 C in controls (P = 0.021, odds ratio = 0.38). An increased frequency of the IL-1 haplotype comprising IL-1A +4845 G, IL-1B -31 C, and IL-1RN +2018 C was observed in controls (P = 0.004). Moreover, a multivariate logistic regression analysis revealed that subjects with IL-1RN +2018 C allele were less likely to have CP (P = 0.016, odds ratio = 0.29). These findings document the association of IL-1RN +2018 C with reduced susceptibility to CP in the Japanese.

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  • Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue 査読

    Takehiko Kubota, Manarni Itagaki, Chika Hoshino, Masaki Nagata, Toshiya Morozumi, Tetsuo Kobayashi, Ritsuo Takagi, Hiromasa Yoshie

    Journal of Periodontology   79 ( 1 )   166 - 173   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: The balance between the degradation and synthesis of extracellular matrix determines periodontal attachment levels and alveolar bone matrix concentration in periodontal diseases. Matrix metalloproteinases (MMPs) are known to degrade periodontal ligamental attachment and bone matrix proteins. The purpose of this study was to examine the effect of different expression levels of MMPs and their inhibitors, the tissue inhibitors of matrix metalloproteinases (TIMPs), in periodontitis.
    Methods: Sixteen inflamed gingival tissue samples from subjects with generalized chronic periodontitis and 14 control tissue samples from systemically and periodontally healthy subjects were evaluated. The total RNA was extracted, and the transcript levels for MMP-1, -3, -9, and -13 and TIMP-1, -2, -3, and -4 relative to P-actin were determined by quantitative real-time reverse transcription - polymerase chain reaction.
    Results: Gene transcript levels for MMP-1 and TIMP-4 were significantly higher in periodontitis-affected gingival tissues (P &lt;0.05). MMP-3, -9, and - 13 and TIMP-1 mRNAs also were elevated in periodontitis; however, the difference was not statistically significant. TIMP-2 and -3 mRNA levels were similar in healthy and diseased gingivae. The ratios of MMP-1 /TIMP-2 (P &lt;0.01), MMP-3/TlMP-2 (P&lt;0.05), MMP-9/TIMP-2 (P&lt;0.05), and MMP-1/TIMP-3 (P&lt;0.01) from periodontitis lesions were significantly higher than those in the control tissues.
    Conclusions: Upregulated MMP expression and an increased MMP/TIMP ratio indicate that a potential imbalance between degradation and synthesis of extracellular matrix persists in periodontitis-affected gingival tissues. This process may be responsible for increased tissue breakdown in periodontitis.

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  • The interleukin-1 and Fc gamma receptor gene polymorphisms in Japanese patients with rheumatoid arthritis and periodontitis 査読

    Tetsuo Kobayashi, Satoshi Ito, Takeshi Kuroda, Kouji Yamamoto, Noriko Sugita, Ichiei Narita, Takayuki Sumida, Fumitake Gejyo, Hiromasa Yoshie

    Journal of Periodontology   78 ( 12 )   2311 - 2318   2007年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: The pathobiology of rheumatoid arthritis (RA) is similar to that of periodontitis in that proinflammatory cytokines and immunoglobulin G Fc receptor (Fc gamma R) play an important role. Functional polymorphisms of interleukin (IL)-1 and Fc gamma R were shown to be associated with susceptibility to both diseases. Therefore, we evaluated whether the IL-1 and Fc gamma R gene polymorphisms represent a common risk factor for RA and periodontitis.
    Methods: The study population consisted of Japanese adults with RA (RA group; N = 100), periodontitis only (P group; N = 100), and healthy individuals with no systemic or oral disease (H group; N = 100). Clinical periodontal condition was defined by measurements of probing depth, clinical attachment level, and bleeding on probing. Genomic DNA was isolated from peripheral blood and analyzed for determination of IL-1 genotypes (IL-1A+4845, IL-1B+3954, and IL-1RN+2028) and Fc gamma R genotypes (Fc gamma RIIA, Fc gamma RIIIA, and Fc gamma RIIIB) by allele-specific polymerase chain reactions.
    Results: Among 100 patients with RA, 86% showed periodontal tissue destruction. However, the RA group exhibited milder levels of periodontal tissue destruction than the P group (P &lt; 0.01). There was a significant difference in the distribution of IL-1B+3954 C/T genotypes between the RA and P groups and between the RA and H groups (P= 0.03 for both comparisons), with enrichment of the T allele in the RA group (P= 0.04; odds ratio, 2.9 for both comparisons). The combination of IL-1A+4845 T and IL-1+3954 T alleles yielded a strong association with RA and periodontitis (RA versus P group: P= 0.00001; RA versus H group: P= 0.00001).
    Conclusions: These results failed to show that IL-1 and Fc gamma R gene polymorphisms constitute a common risk factor for RA and periodontitis. However, it was suggested that the distributions of IL-1B+3954 genotypes and IL-1A+4845 and IL-1B+3954 haplotypes were unique to the patients with RA and periodontitis.

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  • The Fc gamma RIIa polymorphism influences production of interleukin-1 by mononuclear cells 査読

    K. Yamamoto, T. Kobayashi, N. Sugita, H. Tai, H. Yoshie

    International Journal of Immunogenetics   34 ( 5 )   369 - 372   2007年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    The functional bi-allelic polymorphism of immunoglobulin G (IgG) Fc receptor (Fc gamma R) IIa influences the efficiency of human IgG2 binding. Our previous study showed that the high affinity Fc gamma RIIa genotype (-H/H131) was associated with periodontitis risk. As interleukin-1 (IL-1) is one of the major causes of periodontal tissue destruction, it is hypothesized that the Fc gamma RIIa-H/H131cross-linking could induce an increased IL-1 release by mononuclear cells. In this study, we evaluated the intracellular expressions of IL-1 beta in CD14 positive cells upon stimulation with human IgG2 by flow cytometry. Fc gamma RIIa-H/H131 subjects exhibited a higher percentage of IL-1 beta-producing cells than Fc gamma RIIa-R/H131 and -R/R131 subjects (P &lt; 0.05). These results support the concept that Fc gamma RIIa genotype may affect IL-1 beta production, possibly leading to interindividual differences in periodontitis risk.

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  • マイクロサテライトを用いた相関解析による歯周炎感受性遺伝子同定 第19染色体全長の解析

    多部田 康一, 田井 秀明, 小林 哲夫, 島田 靖子, 山崎 和久, 石原 裕一, 野口 俊英, 曽我 賢彦, 高柴 正悟, 小林 輝一, 岡 晃, 猪子 英俊, 吉江 弘正

    新潟医学会雑誌   121 ( 6 )   360 - 361   2007年6月

  • The r40-kDa outer membrane protein human monoclonal antibody protects against Porphyromonas gingivalis-induced bone loss in rats 査読

    Nobushiro Hamada, Kiyoko Watanabe, Tomoyuki Tahara, Kumiko Nakazawa, Isao Ishida, Yasuko Shibata, Tetsuo Kobayashi, Hiromasa Yoshie, Yoshimitsu Abiko, Toshio Umemoto

    Journal of Periodontology   78 ( 5 )   933 - 939   2007年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Porphyrornonas gingivalis has been implicated as an important pathogen in the development of adult periodontitis, and its colonization of subgingival sites is critical in the pathogenic process. We recently reported the construction and characterization of human immunoglobulin G isotype clones, which were specifically reactive with recombinant (r) 40-kDa outer membrane protein (OMP) of P. gingivalis. The aim of this study was to investigate the efficacy of human monoclonal antibody (hMAb) against r40-kDa OMP of P. gingiualisto the protection alveolar bone loss by P. gingivalis in rats.
    Methods: The role of 40-kDa OMP in the adherence of P. gingivalis to human gingival epithelial cells (HGECs) was examined by preincubating with r40-kDa OMP hMAb before adding the HGECs. Moreover, we used a rat model to examine the effect of the anti-r40-kDa OMP hMAb in alveolar bone loss by oral infection. Forty-six days after the last infection, the periodontal bone level was assessed morphometrically on defleshed rat jaws.
    Results: The adherence to HGECs was reduced by 84% compared to adherence levels without the antibody. P. gingivalis could not be detected from rats in a P. gingiva lis-non -infected group and a group that was administered the anti-r40-kDa OMP hMAb. The bone loss in P. gingiualis-infected animals that were administered the anti-r40-kDa OMP hMAb was significantly lower than that of P. gingiva lis-infected rats.
    Conclusions: Our results suggest that transchromosomic mouse-derived hMAb against r40-kDa OMP of P. gingivalis protects against periodontal bone loss. This newly constructed anti-r40-kDa OMP hMAb was used to protect against periodontal diseases caused by P. gingivalis infection.

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  • Salivary enzyme levels after scaling and interleukin-1 genotypes in Japanese patients with chronic periodontitis 査読

    Hiromasa Yoshie, Hideaki Tai, Tetsuo Kobayashi, Emire Oda-Gou, Yoshiaki Nomura, Yukihiro Numabe, Kohichi Ito, Hidemi Kurihara, Kyuichi Kamoi

    Journal of Periodontology   78 ( 3 )   498 - 503   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Saliva has been used as a diagnostic fluid in medicine and dentistry. It is easy to collect using non-invasive methods. The intracellular enzymes present in saliva have been studied as markers of periodontal disease. The purpose of this study was to determine the salivary enzyme levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) after scaling and to clarify the influence of interleukin (IL)-1 genotypes on these enzyme levels.
    Methods: Forty-nine Japanese patients with chronic periodontitis (24 men and 25 women; mean age: 55.1 years) were enrolled in this study. Measurements of clinical parameters including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) and collections of stimulated whole mixed saliva were performed at baseline and 4 weeks after scaling. After evaluation of salivary AST, ALT, and LDH levels, DNA was extracted from various cells in whole saliva. IL-1A+4845 G/T genotype was determined by polymerase chain reaction amplification, followed by enzyme digestion and electrophoresis. Statistical analysis was performed by the Wilcoxon signed-rank and Mann-Whitney U tests. A significant difference was set at P &lt; 0.05.
    Results: Mean PD, CAL, and BOP values significantly decreased after scaling (mean +/- SE: 3.2 +/- 0.1 mm to 2.6 +/- 0.1 mm in PD; 3.9 +/- 0.2 mm to 3.3 +/- 0.2 mm in CAL; and 41% 4% to 18% 3% in BOP) (P &lt; 0.001). The values of AST, ALT, and LDH were 77.0 +/- 7.5, 43.9 +/- 5.5, and 753.4 +/- 96.5 (units per liter [U/l]) at baseline, and significantly decreased to 55.5 +/- 6.5, 30.0 +/- 5.5, and 394.7 +/- 34.0 (U/l) after scaling, respectively (P = 0.01, P = 0.006, and P &lt; 0.001). The carriage rate of the IL-1A+4845 allele 2 was 24.5%. No difference was noted in the decrease in PD, CAL, and BOP after scaling between the carriers (N = 12) and non-carriers (N = 37) of IL-1A+4845 allele 2. However, the IL-1A allele 2 non-carriers displayed a significant decrease in salivary AST and ALT levels (P &lt; 0.001), in contrast to the carriers who did not show any changes in the salivary levels of the enzymes after scaling.
    Conclusions: These results documented that salivary AST, ALT, and LDH levels reflect inflammation and destruction of periodontal tissue, suggesting clinically useful markers following periodontal therapy. In addition, although IL-1A+4845 alleles may not influence clinical parameters, they may influence post-scaling values of salivary AST and ALT.

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  • The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults 査読

    Tetsuo Kobayashi, Satoshi Ito, Keiko Yasuda, Takeshi Kuroda, Kouji Yamamoto, Noriko Sugita, Hideaki Tai, Ichiei Narita, Fumitake Gejyo, Hiromasa Yoshie

    Journal of Periodontology   78 ( 3 )   467 - 474   2007年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (Fc gamma R) and proinflammatory cytokines play an important role. Genetic variations of Fc gamma R and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of Fc gamma R or IL-1 polymorphic genes represents a common risk factor for SLE and periodontitis.
    Methods: The study population consisted of Japanese adults with SLE and periodontitis (SLE+P group; n = 46), SLE only (SLE group; n = 25), periodontitis only (P group; n = 58), and healthy individuals with no systemic or oral disease (H group; n = 44). Clinical periodontal condition was evaluated by measurement of probing depth, clinical attachment level, and alveolar bone loss. Genomic DNA was isolated from peripheral blood and analyzed for determination of Fc gamma R genotypes (Fc gamma RIIA, Fc gamma RlIB, Fc gamma RIIIA, and Fc gamma RIIIB) and IL-1 genotypes (IL-1A +4845 and IL-1B +3954) by allele-specific polymerase chain reactions or DNA sequencing.
    Results: A significant overrepresentation of the R 131 allele of stimulatory Fc gamma RIIA and the 232T allele of inhibitory Fc gamma RIIB was found in the SLE+P group compared to the H group (P=0.01 and P=0.0009, respectively). The combination of Fc gamma RIIA-R131 and Fc gamma RIIB-232T alleles yielded a strong association with SLE and periodontitis (SLE+P group versus P group: P=0.01, odds ratio: 3.3; SLE+P group versus H group: P = 0.0009, odds ratio: 11.2). Furthermore, SLE patients with the combined Fc gamma R risk alleles exhibited more severe periodontal tissue destruction compared to other SLE patients. The frequencies of IL-1 polymorphic alleles were too low to assess the association with SLE or periodontitis.
    Conclusion: The combination of stimulatory Fc gamma RIIA and inhibitory Fc gamma RIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.

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  • The role of genetic polymorphisms in periodontitis 査読

    Hiromasa Yoshie, Tetsuo Kobayashi, Hideaki Tai, Johnah C. Galicia

    Periodontology 2000   43 ( 1 )   102 - 132   2007年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    DOI: 10.1111/j.1600-0757.2006.00164.x

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  • Antibody responses to Porphyromonas gingivalis hemagglutinin A and outer membrane protein in chronic periodontitis 査読

    Tetsuo Kobayashi, Susumu Kaneko, Tomoyuki Tahara, Mitsuo Hayakawa, Yoshimitsu Abiko, Hiromasa Yoshie

    Journal of Periodontology   77 ( 3 )   364 - 369   2006年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Hemagglutinin and outer membrane protein (OMP) are major virulence factors associated with colonization of Porphyromonas gingivalis in the gingival crevice. The genes for the 200-kDa antigenic protein (200-kDa AP) and 40-kDa OMP of P. gingivalis have been successfully cloned. Additionally, the 200-kDa AP gene has been shown to constitute the hemagglutinin A (hagA) gene of P. gingivalis. Therefore, this study was constructed to evaluate the distributions and serum levels of immnoglobulin G (IgG) antibodies specific for 200-kDa AP and 40-kDa OMP in periodontitis patients.
    Methods: Fifty patients with chronic periodontitis and 59 controls without periodontal destruction were enrolled in this study. We cloned the genes for 200-kDa AP and 40-kDa OMP from P. gingivalis and constructed the purified recombinant proteins. Serum levels of IgG subclass antibodies specific for both recombinant 200-kDa and 40-kDa OMP were determined in patients and controls by an enzyme-linked immunosorbent assay (ELISA).
    Results: The serum IgG subclass distribution for patients and controls was IgG1 &gt; IgG4 &gt; IgG2 &gt; IgG3 in the anti-200-kDa AP response, which was almost identical to that in the anti-40-kDa OMP response. The patient group showed significantly higher serum IgG responses to the 40-kDa OMP than the control group (P &lt; 0.01). In contrast, IgG subclass responses to the 200-kDa AP were not different between the patients and controls. Serum levels of antibodies reactive with both 200-kDa and 40-kDa proteins did not have a significant association with mean probing depth.
    Conclusion: These results suggested that serum IgG responses against P. gingivalis OMP rather than the hagA may be more active in chronic periodontitis.

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  • Genetic polymorphisms and periodontitis 査読

    H. Yoshie, J. C. Galicia, T. Kobayashi, H. Tai

    International Congress Series   1284   131 - 139   2005年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Genetically complex diseases like periodontitis have been extensively studied over the past decade. With the pooled knowledge about genetic polymorphisms that were claimed to play a role in the predisposition to and the progression of aggressive and chronic periodontitis, it is now possible to identify candidate genes that could act as potential risk or protective factors for the disease. Genetic researches in periodontitis were generally focused on 1) inflammatory cytokines, 2) cell surface receptors and 3) enzymes and related factors. Our reports have indicated the positive relationship between IgG Fc receptor (Fcγ R) IIIB, Fcγ RIIB, interleukin-1 receptor antagonist (IL-1RN), IgA Fc receptor (Fcα RI) gene polymorphisms and aggressive periodontitis in Japanese. Moreover, variations in the Fcγ RIIIA, Fcγ RIIA, tumor necrosis factor (TNF) receptor 2 and IL-6 gene correlated with the severity of chronic periodontitis. Periodontitis may be explained not only by the presence of specific bacteria and environmental factors, but also by the several relatively common polymorphisms with cumulative high-susceptibility profiles. © 2005 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.ics.2005.06.063

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  • The trans-chromosomic mouse-derived human monoclonal antibody promotes phagocytosis of Porphyromonas gingivalis by neutrophils 査読

    Ayano Takauchi, Tetsuo Kobayashi, Tomoyuki Tahara, Kumiko Nakazawa, Mitsuo Hayakawa, Yasuko Shibata, Isao Ishida, Yoshimitsu Abiko, Hiromasa Yoshie

    Journal of Periodontology   76 ( 5 )   680 - 685   2005年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: As a safe immunotherapeutic approach, human monoclonal antibody (hMAb) may be effective in clearing periodontopathic bacteria. The trans-chromosomic (TC) technology has recently been applied to construction of the TC mouse, which enables us to incorporate entire human chromosome fragments containing immunoglobulin (Ig) gene cluster. The aim of this study is to establish TC mouse-derived hMAb, and to test the in vitro opsonophagocytic activity.
    Methods: Human Ig-producing TC mouse was immunized by recombinant 40-kDa outer membrane protein (r40-kDa OMP) of Porphyromonas gingivalis 381, and the spleen cells were fused with the mouse myeloma cell line. The specificity of anti-r40-kDa OMP hMAb was evaluated with the enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance assays. Flow cytometric analyses were performed to assess the opsonophagocytic activity.
    Results: We successfully constructed 99 IgG isotype clones (IgG 1: 84; IgG2: 11; IgG4: four clones), which were specifically reactive with r4O-kDa OMP. The anti-r40-kDa OMP IgG1 hMAbs promoted phagocytosis of P. gingivalis by neutrophils. Futhermore, an increased opsonophagocytic activitity of anti-r40-kDa OMP IgG1 hMAbs was observed not only in P gingivalis 381, but also in the W50, W83, and Su63 strains.
    Conclusion: Our results document the TC mouse-derived hMAb to promote neutrophil phagocytosis of P. gingivalis, suggesting an immunotherapeutic option for clearance of P. gingivalis.

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  • Fc gamma RIIIb genotypes and smoking in periodontal disease progression among community-dwelling older adults in Japan 査読

    Akihiro Yoshihara, Noriko Sugita, Kouji Yamamoto, Tetsuo Kobayashi, Toshinobu Hirotomi, Hiroshi Ogawa, Hideo Miyazaki, Hiromasa Yoshie

    Journal of Periodontology   76 ( 2 )   250 - 255   2005年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Fc gamma RIIIb genotypes and smoking are risk factors for periodontal disease. However, the interaction of Fc gamma RIIIb-NA1-NA2 polymorphism with smoking remains unclear. The purpose of this study was to determine if Fc gamma RIIIb-NA1-NA2 polymorphism and smoking are associated with periodontal disease progression among elderly people.
    Methods: Among 70-year-old subjects, 164 with neither diabetes mellitus nor blood sugar &gt;= 140 mg/dl, who had more than 20 teeth and who could participate in both the baseline and the follow-up examinations were included in the study. The NA1 group comprised subjects with Fc gamma RIllb-NA1NA1 genotype (N = 53), while the NA2 group included subjects with Fc gamma RIIIb-NA1NA2 or NA2NA2 genotype (N = 111). We examined the progression of periodontitis by measuring attachment loss during 3 years.
    Results: The frequency of subjects who showed &gt;= 4 mm additional attachment loss at one or more sites was 55.6% for smokers and 37.2% for non-smokers. The odds ratio (OR) was 2.13 (confidence interval [CI]: 0.92 to 4.76). We found a better association between periodontal progression and smoking in the NA2 group. The OR for smokers was 3.03 (CI: 1.12 to 8.33, P = 0.028). Additionally, the mean number of sites with &gt;= 4 mm additional attachment loss per person between smokers and non-smokers in the NA2 group or between smokers and non-smokers in the NA1 group was 2.90 +/- 3.42 and 0.74 +/- 1.53 or 0.57 +/- 0.79 and 0.68 +/- 1.03, respectively (P &lt; 0.001; analysis of variance [ANOVA]).
    Conclusion: Our results may suggest an association between smoking and periodontal disease progression in elderly people with Fc gamma RIIIb-NA2 polymorphism.

    DOI: 10.1902/jop.2005.76.2.250

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  • Targeting of Porphyromonas gingivalis with a bispecific antibody directed to Fc alpha RI (CD89) improves in vitro clearance by gingival crevicular neutrophils 査読

    Tetsuo Kobayashi, Ayano Takauchi, Annemiek B. van Spriel, Henriette A. Vil ́e, Mitsuo Hayakawa, Yasuko Shibata, Yoshimitsu Abiko, Jan G.J, van de Winkel, Hiromasa Yoshie

    Vaccine   23 ( 5 )   585 - 594   2004年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Phagocytosis and killing of pathogens by polymorphonuclear neutrophils (PMN) from gingival crevicular fluid (GCF) is diminished in chronic periodontitis patients. As an approach to improve tar of PMN toward a periodontopathogen. Porphyromonas gingivalis, the efficacy of a bispecific antibody (BsAb) directed against both recombinant 130 kDa hemagglutinin domain (r130k-HMGD) of P. gingivalis, and PMN Fc receptor (FcR) was evaluated. GCF PMN exhibited higher IgA FcR (FcalphaRI) levels. and lower IgG FcR (FegammaRIIa and FcgammaRIIIb) levels than PB PMN. Functional studies revealed that GCF PMN exhibited a higher capacity to phagocytose and kill P gingivalis opsonized with a BsAb targeting P. gingivalis r130k-HMGD to FcalphaRI as compared to an anti-r130k-HMGD antibody. However. phagocytosis and killing activity of PB PMN that were incubated with the two antibodies proved comparable. These data support targeting of pathogens toward FcalphaRI as an option to improve antibacterial immunity in chronic periodontitis patients. (C) 2004 Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.vaccine.2004.07.015

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  • A novel polymorphism of Fc alpha RI (CD89) associated with aggressive periodontitis 査読

    S Kaneko, T Kobayashi, K Yamamoto, MD Jansen, JGJ van de Winkel, H Yoshie

    Tissue Antigens   63 ( 6 )   572 - 577   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Immunoglobulin A Fc receptor (FcalphaRI) has been implicated in the pathogenesis of periodontitis, because increased IgA responses and FcalphaRI-bearing neutrophils are observed in the disease lesions. Inter-individual differences in susceptibility to periodontitis may be attributable to genetic variability in FcalphaRI-mediated immunity. We here identified an FcalphaRI novel polymorphism (nt 324 A-to-G transition) in the membrane-distal extracellular domain encompassing the ligand-binding site, not resulting in an amino acid change. We compared the FcalphaRI genotype distributions among 46 Japanese aggressive periodontitis (AGP) patients, 80 race-matched healthy controls (HCs), and 59 Caucasian HCs. No ethnic differences were observed in the FcalphaRI genotype distributions between Japanese and Caucasian HC. Notably, we observed a difference in the genotype distribution between the AGP and HC groups. Carriage rate of the nt 324 A allele was higher in the AGP (65.2%) than that in the HC group (42.5%) (odds ratio 2.54). Polymorphonuclear neutrophils from peripheral blood and gingival crevicular fluid exhibited a decreased phagocytosis of periodontopathic bacteria (Porphyromonas gingivalis) in the nt 324 A/A patients as compared with the nt 324 G/G patients. These results document a genetic polymorphism at the FcalphaRI ligand-binding site to be associated with susceptibility to AGP.

    DOI: 10.1111/j.0001-2815.2004.0228.x

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  • Association of tumor necrosis factor receptor type 2+587 gene polymorphism with severe chronic periodontitis 査読

    Y Shimada, H Tai, M Endo, T Kobayashi, K Akazawa, K Yamazaki

    Journal of Clinical Periodontology   31 ( 6 )   463 - 469   2004年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Background: Genetic polymorphisms for cytokines and their receptors have been proposed as potential markers for periodontal disease. Tumor necrosis factor receptor 2 (TNFR2) is one of the cell surface receptors for TNF-alpha. Recent studies have suggested that TNFR2 gene polymorphism is involved in autoimmune and other diseases.
    Objectives: The aim of the present study is to evaluate whether TNFR2(+587T/G) gene polymorphism is associated with chronic periodontitis (CP).
    Methods: One hundred and ninety-six unrelated subjects (age 40-65 years) with different levels of CP were identified according to established criteria, including measurements of probing pocket depth (PPD), clinical attachment level (CAL), and alveolar bone loss (BL). All subjects were of Japanese descent and non-smokers. Single nucleotide polymorphism at position +587(T/G) in the TNFR2 gene was detected by a polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method.
    Results: The frequency and the positivity of the +587G allele were significantly higher in severe CP patients than in controls (p=0.0097; odds ratio=2.61, p=0.0075; odds ratio=3.06). In addition, mean values of PPD, CAL, and BL were significantly higher in the +587G allele positive than in the negative subjects (p=0.035, 0.022, and 0.018, respectively).
    Conclusions: These findings suggest that the TNFR2(+587G) polymorphic allele could be associated with severe CP in Japanese.

    DOI: 10.1111/j.1600-051X.2004.00513.x

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  • Interleukin-4 gene polymorphisms in Japanese and Caucasian patients with aggressive periodontitis 査読

    Gonzales, JR, T Kobayashi, J Michel, M Mann, H Yoshie, J Meyle

    Journal of Clinical Periodontology   31 ( 5 )   384 - 389   2004年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Objectives: Recently, interleukin (IL) 4 gene polymorphisms have been analyzed in association with periodontitis. Genetic differences between Caucasian and Japanese patients with periodontitis have previously been detected. The aim of the present study was to analyze IL-4 genotypes in Caucasian and Japanese patients with aggressive periodontitis (AgP).
    Material and Methods: One hundred and twenty-four subjects were included in the study, 31 Japanese and 30 Caucasian patients with generalized AgP, plus 30 Japanese and 33 Caucasian healthy controls. IL-4 polymorphisms were determined by polymerase chain reaction. A logistic regression was used to investigate the possible association of the genotypes with the disease in both populations. Odds ratio (OR) estimates were analyzed for allele frequencies.
    Results: No significant association of IL-4 polymorphisms with the risk of AgP was determined in either population. However, the allele frequencies showed different results between populations. The carriage of the polymorphism in intron 2 was higher in Caucasian patients compared with controls (OR: 2.0, 95% confidence interval: [1.0;4.2]. Furthermore, the frequency of the IL-4 promoter/intron 2 composite genotype (PP+/IP+) in patients and controls, respectively, was found to be approximately 25% and 60% higher in the Japanese population than in the Caucasian population.
    Conclusion: There was no evidence of an association of IL-4 genotypes and AgP in either population, although the frequencies of the IL-4 genotypes in the Japanese and the Caucasians were different.

    DOI: 10.1111/j.1600-051X.2004.00492.x

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  • Association of Fc gamma receptor IIa genotype with chronic periodontitis in Caucasians 査読

    Kouji Yamamoto, Tetsuo Kobayashi, Sara Grossi, Alex Ho, Robert J. Genco, Hiromasa Yoshie, Ernesto De Nardin

    Journal of Periodontology   75 ( 4 )   517 - 522   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors IIIa and IIIb (FcgammaRIIIa and FcgammaRIIIb) have been shown as risk factors for periodontitis. The aim of this study is to examine whether FcgammaRIIa polymorphism is associated with a disease risk as well.
    Methods: Baseline periodontal and general health examinations were carried out on 1,221 Caucasian adults. From these, 422 subjects with moderate to severe, or little or no periodontal disease were assigned to two groups according to their mean clinical attachment loss (CAL). Subjects with mean CAL greater than or equal to2.94 mm were diagnosed with chronic periodontitis (n = 213, 62 never-smokers and 151 smokers). Subjects with mean CAL less than or equal to1.77 mm were considered as having little or no periodontal disease and designated as controls (n = 209, 125 never-smokers and 84 smokers). The FcgammaRIIa genotype for three bi-allelic polymorphisms (FcgammaRIIa-R/ R131, R/H131, and H/H131) was determined by means of allele-specific polymerase chain reactions.
    Results: The distribution of FcgammaRIIa genotype between the patient and control groups was significantly different, with enrichment of the high ligand-binding genotype FcgammaRIIa-H/H131 in the patients (patients versus controls: 36.6% versus 25.4%; P= 0.04). Multivariate logistic regression model demonstrated that subject age and gender, smoking, and the FcgammaIIa genotype were significantly associated with severity of chronic periodontitis. For smokers, a significant over-representation of FcgammaRIIa-H/H131 in the patient group compared to the control group (patients versus controls: 35.1% versus 19.0%; P= 0.03). Additionally, smokers with FcgammaRIIa-H/H131 exhibited significantly greater mean CAL (mean +/- SE: 3.44 +/- 0.16 mm) than those with FcgammaRIIa-R/H131 (2.91 +/- 0.14 mm) and R/R131 (2.82 +/- 0.16 mm) (P = 0.04). There was no association between FcgammaRIIa genotype and the disease susceptibility or severity in subjects who had never smoked.
    Conclusions: Our results suggest that the Fc7RIIa-H/H131 genotype may be associated with chronic periodontitis risk (and disease severity) in Caucasian smokers. Further studies with families and studies of mechanisms are necessary to help establish the extent to which this is a genetic determinant of periodontal diseases.

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  • Fc gamma RIIB gene polymorphisms in Japanese periodontitis patients 査読

    K Yasuda, N Sugita, T Kobayashi, K Yamamoto, H Yoshie

    Genes and Immunity   4 ( 8 )   541 - 546   2003年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Human type II low-affinity receptor for immunoglobulin G (FcgammaRII) constitutes a clustered gene family consisting of FcgammaRIIA, IIB and IIC genes. FcgammaRIIB is unique in its ability to transmit inhibitory signals in B cells via immunoreceptor tyrosine-based inhibitory motif (ITIM). B-cell activation and subsequent elevated production of IgG are the immunopathological features of inflammatory disease such as periodontitis. To determine whether an association with periodontitis susceptibility exists, genetic polymorphisms of FcgammaRIIB were examined in Japanese patients with aggressive periodontitis (AGP) and chronic periodontitis (CP), and in the race-matched healthy controls (HCs). A significant difference was observed in the distribution of FcgammaRIIB - 232I/T allele (exon 5) between the AGP and HC groups, with enrichment of the 232T in the AGP group (P = 0.006). In addition, the FcgammaRIIB- nt 646 - 184A/G allele (intron 4) distribution was significantly different between the CP and HC groups, with enrichment of the nt 646 - 184A in the CP group (P = 0.011). These results document the association of FcgRIIB gene polymorphisms with susceptibility to periodontitis in the Japanese.

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  • TNF レセプター1型および2型遺伝子多型と広汎性侵襲性歯周炎の関連性について

    島田 靖子, 田井 秀明, 遠藤 基広, 小林 哲夫, 山崎 和久, 吉江 弘正

    日本歯周病学会会誌   45 ( 3 )   267 - 278   2003年9月

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    記述言語:日本語   出版者・発行元:JAPANESE SOCIETY OF PERIODONTOLOGY  

    歯周炎は多因子疾患の一つと考えられ, なかでも侵襲性 (早期発症型) 歯周炎の疾患感受性には遺伝子多型の関与が示唆されている。一方で, 歯周炎局所でTNFαのシグナル伝達・調節機能を担うTNFレセプター (TNFR) の機能についても着目されている。そこで今回, 日本人におけるTNFRの遺伝子多型と侵襲性歯周炎との関連性について検討した。<BR>インフォームドコンセントを得た日本人広汎性侵襲性歯周炎患者45名および年齢を適合させた健常者100名を対象とした。5カ所の遺伝子多型はそれぞれTNFR2 (VNTR) はPCR法, TNFR1 (-383; A/C), (+36; A/G), TNFR2 (+587; T/G) はPCR-RFLP法, TNFR2 (+694; G/A) はPCR-SSCP法にて検出した。統計学的解析はカイ2乗検定, フィッシャーの直接確率法, 同等性のΔ検定とさらにMante1-Haensze1法による補正を行った。<BR>その結果, TNFR1 (-383) ではCアレルの頻度が患者群に有意に低いことを認めた。さらに患者群と健常者群では, 3カ所のTNFR2アレル頻度に同等性が認められ, 交絡因子で補正後もTNFR2 (+587) および (VNTR) には同等性が有意に認められた。<BR>以上の結果より, 広汎性侵襲性歯周炎にはTNFR1 (-383) 遺伝子多型が関連する一方で, TNFR2 (+587), (VNTR) には関連性が乏しい可能性が示唆された。

    DOI: 10.2329/perio.45.267

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  • Evidence for non-random distribution of Fc gamma receptor genotype combinations 査読

    WL van der Pol, MD Jansen, WJ Sluiter, B van de Sluis, FGJ Leppers-van de Straat, T Kobayashi, RGJ Westendorp, TWJ Huizinga, JGJ van de Winkel

    Immunogenetics   55 ( 4 )   240 - 246   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER-VERLAG  

    Human IgG receptors (FcgammaR) display considerable heterogeneity, and are crucial immune response modulating molecules. FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB display functional biallelic polymorphisms. FcgammaR polymorphisms have been found associated with susceptibility to infectious and autoimmune diseases. Linked transmission of FcgammaR alleles was studied by determining the distribution of FcgammaRIIA-FcgammaRIIIA-FcgammaRIIIB genotype combinations in 514 Dutch Caucasian, and 149 Japanese blood donors. The structure of the FcgammaR locus was studied by radiation hybrid mapping of FcgammaRIA, FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, FcgammaRIIIB, and adjacent genes from the pentraxin family. In addition, crossing-over frequencies within the FcgammaR locus were determined in 63 Dutch Caucasian families, encompassing 183 individuals. FcgammaRII and FcgammaRIII subclasses were mapped in close proximity (0.47-3.14 cR). Accordingly, crossing-over frequencies within the FcgammaRII-III locus in Dutch families were low. Analysis of combined FcgammaR genotypes strongly suggested non-random distribution of FcgammaRIIA-FcgammaRIIIA-, and FcgammaRIIIA-FcgammaRIIIB genotypes in Dutch donors (P&lt;0.001 and P&lt;0.00001, respectively), and of FcgammaRIIA-FcgammaRIIIb genotypes in Japanese blood donors (P&lt;0.02). Frequencies of FcgammaRII-FcgammaRIII haplotypes differed significantly between Dutch and Japanese (P&lt;0.00001). This study provides important information for the interpretation of studies reporting associations of FcgammaR alleles with disease, and underscores the apparent differences in FcgammaR heterogeneity between ethnic groups.

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  • Risk of periodontitis in systemic lupus erythematosus is associated with Fc gamma receptor polymorphisms 査読

    Tetsuo Kobayashi, Satoshi Ito, Kouji Yamamoto, Hisashi Hasegawa, Noriko Sugita, Takeshi Kuroda, Susumu Kaneko, Ichiei Narita, Keiko Yasuda, Masaaki Nakano, Fumitake Gejyo, Hiromasa Yoshie

    Journal of Periodontology   74 ( 3 )   378 - 384   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Leukocyte Fc receptors for immunoglobulin G (FcgammaR) play a major role in the handling of immune complexes and pathogens in systemic lupus erythematosus (SLE) and periodontitis. Both diseases have been shown to be partly influenced by genetic components including FcgammaR genotype. The aim of this study was therefore to evaluate whether FcgammaR gene polymorphisms are associated with periodontitis risk in SLE patients.
    Methods: The study subjects consisted of 42 SLE patients with periodontitis (SLE/P), 18 SLE patients without periodontitis (SLE/H), 42 healthy subjects with periodontitis (H/P), and 42 healthy subjects without periodontitis (H/H), who were all unrelated Japanese non-smokers. Genomic DNA was isolated from peripheral blood, and FcgammaR genotypes for 3 biallelic polymorphisms (FcgammaRIIa-R131/H131, FcgammaRIIIa-158V/158F, FcgammaRIIIb-NA1/NA2) were determined by allele-specific polymerase chain reactions.
    Results: The SLE/P group was found to have more mild levels of periodontal destruction than the H/P group (P &lt; 0.01). There was a significant difference in the distribution of FcgammaRIIa genotypes between SLE/P and H/H groups (P = 0.004). A significant overrepresentation of the FcgammaRIIa-R131 allele was found in the SLE/P group compared to the H/H group (SLE/P versus H/H: odds ratio [OR] 3.13, 95% confidence interval [CI] 1.46-6.77, P = 0.0013). Furthermore, the prevalence of periodontitis was found to be 70% in SLE patients. The FcgammaRIIa-R131 allele was also found to be overrepresented in the SLE/P group compared to the SLE/H group (SLE/P versus SLE/H: OR 3.40, 95% CI 1.18-10.25, P = 0.011).
    Conclusion: These results show the FcgammaRIIa-R131 allele to be associated with periodontitis risk in SLE patients.

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  • Effects of Nd : YAG and CO2 laser treatment and ultrasonic scaling on periodontal pockets of chronic periodontitis patients 査読

    Akira Miyazaki, Toshikazu Yamaguchi, Jun Nishikata, Kazuhiro Okuda, Satoru Suda, Kazuko Orima, Tetsuo Kobayashi, Kazuhisa Yamazaki, Eiji Yoshikawa, Hiromasa Yoshie

    Journal of Periodontology   74 ( 2 )   175 - 180   2003年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: The aim of the present study was to compare the effectiveness of Nd:YAG and CO2 laser treatment to that of ultrasonic scaling used as monotherapies by examining clinical parameters, subgingival microflora, and interleukin-1 beta (IL-1beta) in gingival crevicular fluid (GCF).
    Methods: Eighteen patients, each of whom had 2 or more sites with probing depth measuring &gt;5 mm, were included this clinical trial. The 41 sites were randomly assigned treatment with either Nd:YAG laser alone (n = 14, 100 mj, 20 pps, 2.0 W, 120 seconds), CO2 laser alone (n = 13, 2.0 W, 120 seconds), or ultrasonic scaling alone (n = 14, maximum power, 120 seconds). At baseline and at 1, 4, and 12 weeks, clinical measurements (plaque index, PI; gingival index, GI; probing depth, PD; clinical attachment level, CAL; and bleeding on probing, BOP) were performed and subgingival plaque and GCF sampled. A quantitative analysis of Porphyromonas gingivalis was carried out using real-time polymerase chain reaction (PCR) procedures. The amounts of lL-1beta were estimated by an enzyme-linked immunosorbent assay (ELISA).
    Results: Decreased inflammation and PD were observed in all 3 groups after treatment. A microbiological analysis indicated significant decreases in P gingivalis in the Nd:YAG and scaling groups at 1, 4, and 12 weeks compared to baseline (P&lt;0.05). The amount of GCF significantly decreased in the Nd:YAG and scaling groups at 12 weeks. The amount of IL-1beta increased in the CO2 group from baseline to 1 week (P &lt;0.05). The Nd:YAG group tended to show a decrease in IL-1beta from 1 to 12 weeks, although these data were not statistically significant.
    Conclusions: Our data suggest that Nd:YAG laser and ultrasonic scaling treatments showed significant improvements regarding the clinical parameters and subgingival microflora compared to the baseline, but no significant difference was observed between the 3 groups.

    DOI: 10.1902/jop.2003.74.2.175

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  • Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese 査読

    Hideaki Tal, Motohiro Endo, Yasuko Shimada, Emire Gou, Kazuko Orima, Tetsuo Kobayashi, Kazuhisa Yamazaki, Hiromasda Yoshie

    Journal of Clinical Periodontology   29 ( 10 )   882 - 888   2002年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Background/Aims: Early onset periodontitis (EOP), newly 'aggressive periodontitis', is considered to have genetic basis, which have not been clearly defined. The interleukin-1 (IL-1) gene cluster polymorphism as one of genetic factors may influence the expression of several chronic inflammatory diseases. The aim of this study is to investigate the frequency of single nucleotide polymorphisms (SNPs) in the genes encoding IL-1alpha, IL-1beta and a variable number of tandem repeat (VNTR) polymorphisms in the IL-1 receptor antagonist gene (IL-1RN) in 47 generalized EOP (G-EOP) patients and 97 periodontally healthy controls.
    Material and methods: All subjects were of Japanese descent and systemically healthy. They were identified according to established clinical criteria. SNPs in the IL-1alpha (+4845) and IL-1beta (-511, +3954) genes were analyzed by amplifying the polymorphic region using polymerase chain reaction (PCR), followed by restriction-enzyme digestion and agarose gel electrophoresis. IL-1RN (VNTR) polymorphisms were then detected by PCR amplification and fragment size analysis.
    Results: There was no significant difference in the IL-alpha (+4845) and IL-1beta (-511, +3954) genotypes and allele frequencies between G-EOP patients and healthy controls. However, the frequency of IL-1RN (VNTR) polymorphic alleles was found to be significantly increased in G-EOP patients (chi(2) test, P=0.007; odds ratio=3.40). Additionally, the carriage rate of IL-1RN (VNTR) polymorphisms was significantly higher in G-EOP patients than in healthy controls (chi(2) test, P=0.005; odds ratio=3.81).
    Conclusion: These findings suggest that IL-1RN (VNTR) polymorphisms are associated with G-EOP in Japanese.

    DOI: 10.1034/j.1600-051X.2002.291002.x

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  • Analysis of vitamin D and Fc gamma receptor polymorphisms in Japanese patients with generalized early-onset periodontitis 査読

    A Yoshihara, N Sugita, K Yamamoto, T Kobayashi, H Miyazaki, H Yoshie

    Journal of Dental Research   80 ( 12 )   2051 - 2054   2001年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Early-onset periodontitis (EOP) is considered to have a genetic basis which has not been clearly defined. Genetic polymorphisms of the vitamin D receptor (VDR-B-b) and the immunoglobulin-Fcgamma receptor IIIb (FcgammaRIIIb-NA1-NA2) are associated with bone metabolism and infectious diseases, respectively. The purpose of this study was to investigate the associations of EOP with VDR and FcgammaRIIIb polymorphisms. Subjects were comprised of those with generalized EOP (G-EOP, n = 42), adult periodontitis (AP, n = 52), and healthy control (HC, n = 55). VDR and FcgammaRIIIb genotypes were determined by allele-specific polymerase chain-reactions. Our results indicated that frequencies of the VDR-B non-carrier and the FcgammaRIIIb-NA2 carrier were lower in the G-EOP compared with the AP and HC groups. Furthermore, we found a strong association between G-EOP and the VDR-FcgammaRIIIb composite genotype (G-EOP vs. AP - OR = 5.09, p = 0.009; G-EOP vs. HC - OR = 5.93, p = 0.004). In conclusion, no correlation was found between the VDR genotype and G-EOP. However, the VDR and FcgammaRIIIb genotype combination may be associated with susceptibility to G-EOP.

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  • 日本人早期発症型歯周炎患者におけるTNF-α5'側領域遺伝子多型の解析

    遠藤 基広, 田井 秀明, 多部田 康一, 小林 哲夫, 山崎 和久, 吉江 弘正

    新潟歯学会雑誌   31 ( 2 )   230 - 230   2001年12月

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    記述言語:日本語   出版者・発行元:新潟歯学会  

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  • Seven single nucleotide substitutions in human Fc gamma receptor IIB gene 査読

    K Yasuda, N Sugita, K Yamamoto, T Kobayashi, H Yoshie

    Tissue Antigens   58 ( 5 )   339 - 342   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL MUNKSGAARD  

    Variation screening for the immunoglobulin G Fc receptor IIB (FcgammaRIIB) gene was performed with the genomic DNA from 100 healthy Japanese subjects. We identified 3 non-synonymous and 2 synonymous substitutions and 2 single-nucleotide polymorphisms in an intron region. These substitutions were found to be located in the ligand-binding domain and the intron, which might alter the function of FcgammaRIIb.

    DOI: 10.1034/j.1399-0039.2001.580509.x

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  • Analysis of single nucleotide polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in Japanese patients with early-onset periodontitis 査読

    Motohiro Endo, Hideaki Tai, Koichi Tabeta, Tetsuo Kobayashi, Kazuhisa Yamazaki, Hiromasa Yoshie

    Journal of Periodontology   72 ( 11 )   1554 - 1559   2001年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    Background: Early-onset periodontitis (EOP) is considered to have a genetic basis, which has not been clearly defined. The tumor necrosis factor-alpha (TNF-alpha) gene polymorphism as one of the genetic factors may influence the expression of several chronic inflammatory diseases. The aim of the present study was to evaluate whether the polymorphisms in the 5'-flanking region of the TNF-alpha gene are associated with Japanese EOP patients.
    Methods: Forty-six Japanese, generalized EOP (G-EOP) patients and 104 Japanese healthy subjects were identified according to established clinical criteria. Twenty healthy subjects were analyzed by nucleotide sequence to screen polymorphisms of the 5'-flanking region of the TNF-alpha gene. Then, all subjects were analyzed by polymerase chain reaction and sequencespecific oligonucleotide probe (SSOP) methods.
    Results: We determined 5 single nucleotide polymorphisms at positions - 1031 (T/C), -863 (C/A), -857 (C/T), -308 (G/A), and -238 (G/A) in the 5'-flanking region of the TNF-alpha gene. There were no significant differences in the genotype and allele frequency when we compared G-EOP patients to healthy subjects. Because the frequency of polymorphic alleles at positions -308 and -238 was very low in this study population, we demonstrated the existence of 4 detected haplotypes and 6 detected genotypes concerning 3 single nucleotide polymorphisms (-1031, -863, and -857). The frequency of the H1/H3 (TCC/TCT)-detected genotype tended to decrease in G-EOP patients compared to healthy subjects, but was not statistically significant.
    Conclusion: These findings suggest there is no significant association between polymorphisms in the 5'-flanking region of the TNF-alpha gene and susceptibility to G-EOP in Japanese patients.

    DOI: 10.1902/jop.2001.72.11.1554

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  • The Fcγ Receptor Genotype as a Severity Factor for Chronic Periodontitis in Japanese Patients. 査読

    Tetsuo Kobayashi, Kouji Yamamoto, Noriko Sugita, W-Ludo van der Pol, Keiko Yasuda, Susumu Kaneko, Jan G.J, van de Winkel, Hiromasa Yoshie

    Journal of Periodontology   72 ( 10 )   1324 - 1331   2001年10月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1902/jop.2001.72.10.1324

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  • Effective in vitro clearance of Porphyromonas gingivalis by Fcα receptor I (CD89) on gingival crevicular neutrophils 査読

    Infection and Immunity   69 ( 5 )   2935 - 2942   2001年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1128/IAI.69.5.2935-2942.2001

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  • Evidence for a novel polymorphism affecting both N-linked glycosylation and ligand binding of the IgG receptor IIIB (CD16) 査読

    K Yamamoto, N Sugita, T Kobayashi, K Okuda, JGJ van de Winkel, H Yoshie

    Tissue Antigens   57 ( 4 )   363 - 366   2001年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    Immunoglobulin G Fc receptor mb (Fc gamma RIIIb) is constitutively expressed on neutrophils, and has three allelic forms: Fc gamma RIIIb-NA1, Fc gamma RIIIb-NA2, and Fc gamma RIIIb-SH. We identified two Japanese subjects in whom an A to G substitution at nt 221 changes asparagine (N) to serine (S) at amino acid position 45 in the Fc gamma RIIIb-NA2 gene. Fc gamma RIIIb-NA2-specific mono-clonal antibodies (GRM1 and PEN1) did not bind to mutant neutrophils, which lack an N-linked glycosylation site. Furthermore, IgG3-mediated neutrophil phagocytosis by mutant was slightly increased as compared to wildtype donors.

    DOI: 10.1034/j.1399-0039.2001.057004363.x

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  • Increased frequency of Fc gamma RIIIb-NA1 allele in periodontitis-resistant subjects in an elderly Japanese population 査読

    N Sugita, T Kobayashi, Y Ando, A Yoshihara, K Yamamoto, JGJ van de Winkel, H Miyazaki, H Yoshie

    Journal of Dental Research   80 ( 3 )   914 - 918   2001年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC DENTAL RESEARCH  

    Many elderly people show minimum periodontal tissue destruction, which might be partly due to genetic advantages in host immune response against periodontopathic bacteria. The human IgG Fc receptor IIIb on neutrophils bears a NA1-NA2 polymorphism. The Fc gamma RIIIb-NA1 displays a more efficient interaction with IgG1- and IgG3-opsonized bacteria, compared with the Fc gamma RIIIb-NA2. We investigated a 70-year-old Japanese population (n = 599) to determine whether the Fc gamma RIIIb polymorphism was associated with resistance to periodontitis. Among subjects with greater than or equal to 20 teeth present, periodontitis-resistant (n = 46) and periodontitis-susceptible groups (n = 73) were selected based on the percentage of sites with greater than or equal to 4 nim probing attachment loss in the entire dentition. The Fc gamma RIIIb-NA1 allotype was overrepresented in the periodontitis-resistant group, compared with the periodontitis-susceptible group (chi (2) = 4.89, p = 0.03, odds ratio = 1.87, 95% CI, 1.07 to 3.28). This suggests that Fc gamma RIIIb-NA1 may be associated with resistance to periodontitis.

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  • The Fcγ Receptor Genotype as a Risk Factor for Generalized Early-Onset Periodontitis in Japanese Patients. 査読

    Tetsuo Kobayashi, Noriko Sugita, W-Ludo van der Pol, Yasuko Nunokawa, Nomdo A.C. Westerdaal, Kouji Yamamoto, Jan G..J, van de Winkel, Hiromasa Yoshie

    Journal of Periodontology   71 ( 9 )   1425 - 1432   2000年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1902/jop.2000.71.9.1425

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  • A novel PCR-based method for direct Fcγ receptor IIIa (CD16) allotyping 査読

    F. G J Leppers-Van De Straat, W-L. Van Der Pol, M. D. Jansen, N. Sugita, H. Yoshie, T. Kobayashi, J. G J Van De Winkel

    Journal of Immunological Methods   242 ( 1-2 )   127 - 132   2000年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Leukocyte IgG receptors (FcγR) are important immune-response modulating molecules. FcγRIIIa is expressed on macrophages, NK-cells and γδ-T cells and exhibits a genetically determined, functional polymorphism at nucleotide 559. This allelic difference predicts either a phenylalanine (F158) or valine (V158) at amino acid 158 in the membrane-proximal extracellular domain, and has been shown to be associated with autoimmune and infectious diseases. Published methods to determine FcγRIIIa genotypes are cumbersome. Therefore, we developed a novel, rapid and reliable PCR-based method to determine FcγRIIIa genotypes. Comparison of genotyping results with direct FcγRIIIa sequencing of 60 blood donors showed 100% accuracy of this new method. Since genotype frequencies of FcγR polymorphisms depend strongly on race and ethnicity, we compared FcγRIIIa genotype frequencies of 176 Caucasian Dutch and 104 Japanese blood donors. Interestingly, these frequencies were not significantly different (P&gt
    0.1), in contrast to the FcγRIIa and FcγRIIIb genotype frequencies (P&lt
    0.001). (C) 2000 Elsevier Science B.V.

    DOI: 10.1016/S0022-1759(00)00240-4

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  • Relevance of IgG receptor IIIb (CD16) polymorphism to handling of Porphyromonas gingivalis: implications for the pathogenesis of adult periodontitis 査読

    Tetsuo Kobayashi, W-Ludo van der Pol, Jan G.J, van de Winkel, Kohji Hara, Noriko Sugita, Nomdo A.C. Westerdaal, Hiromasa Yoshie, Tsuneyoshi Horigome

    Journal of Periodontal Research   35 ( 2 )   65 - 73   2000年4月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    Polymorphonuclear neutrophils (PMNs) are essential in host defense against periodontopathic bacteria such as Porphyromonas gingivalis. The uptake of immunoglobulin G (IgG)-opsonized bacteria via IgG Fc receptors (Fc gamma R) on PMN constitutes a central defense mechanism in periodontium. Fc gamma RIIIb is the most abundantly expressed Fc gamma R on PMN and is functionally polymorphic. The Fc gamma RIIIb-NA1 and IIIb-NA2 allotypes interact differently with IgG1- and IgG3-opsonized particles. We recently showed recurrence rates of adult periodontitis (AP) to be higher in patients carrying at least 1 Fc gamma RIIIb-NA2 allele. In this study we evaluated the functional relevance of the Fc gamma RIIIb polymorphism to anti-P. gingivalis PMN effector functions. Our results showed Fc gamma RIIIb-NA2-carrying PMN from both patients with AP and healthy controls to be less efficient in phagocytosis and induction of oxidative burst upon interaction with IgG1- and IgG3-opsonized P. gingivalis. These functional differences between Fc gamma RIIIb-NA1 and IIIb-NA2 were observed in the presence of CD32-blocking antibody fragments, but not upon blocking CD16. Moreover, PMNs from AP patients exhibited increased Fc gamma RIIIb-allelic differences in IgG3-induced oxidative burst compared to control PMNs. These results support the concept that Fc gamma RIIIb heterogeneity may influence the clinical course of AP.

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  • Relevance of Fc gamma RIIIa-158V-F polymorphism to recurrence of adult periodontitis in Japanese patients 査読

    N Sugita, K Yamamoto, T Kobayashi, WL Van der Pol, T Horigome, H Yoshie, JGJ Van de Winkel, K Hara

    Clinical and Experimental Immunology   117 ( 2 )   350 - 354   1999年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE LTD  

    The immunoglobulin receptor Fc gamma RIIIa (CD16) is distributed on natural killer (NK) cells, macrophages, and gamma delta T cells, and is polymorphic. Fc gamma RIIIa-158V has a higher affinity for both monomeric and immune complexed IgG1, IgG3, and IgG4 than IIIa-158F. We determined Fc gamma RIIIa-158V/F genotypes of Japanese patients with adult periodontitis. A significant over-representation of Fc gamma RIIIa-158F was found in patients with recurrence, compared with patients without recurrence, making Fc gamma RIIIA a candidate gene for recurrence risk of adult periodontitis.

    DOI: 10.1046/j.1365-2249.1999.00984.x

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  • Relevance of immunoglobulin G Fc receptor polymorphism to recurrence of adult periodontitis in Japanese patients 査読

    Tetsuo Kobayashi, Nomdo A.C. Westerdaal, Akira Miyazaki, W-Ludo van der Pol, Takashi Suzuki, Hiromasa Yoshie, Jan G.J, van de Winkel, Kohji Hara

    Infection and Immunity   65 ( 9 )   3556 - 3560   1997年9月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    Polymorphonuclear neutrophil (PMN) phagocytic function has been shown to be impaired in some patients with periodontitis. PMN constitutively express members of two immunoglobulin G receptor (Fc gamma R) classes: Fc gamma RIIa (CD32) and Fc gamma RIIIb (CD16), Both receptors exhibit genetically determined structural and functional biallelic polymorphisms, which have been shown to influence PMN phagocytic function, In this study, we assessed the relevance of these Fc gamma R polymorphisms to susceptibility to adult periodontitis and recurrence rate, The distribution of Fc gamma RIIa and Fc gamma RIIIb genotypes of 100 Japanese patients with adult periodontitis during follow-up was compared to the distribution of genotypes in 105 race-matched healthy controls, No significant skewing of distributions of Fc gamma RIIa and Fc gamma RIIIb genotypes was observed between patients and controls, Notably, however, a significant overrepresentation of the Fc gamma RIIIb-NA2 allotype was found in patients with disease recurrence (P &lt; 0.05; odds ratio, 4.29; 95% confidence interval, 1.19 to 16.24), Moreover, the annual rate of recurrence was significantly higher in patients with the Fc gamma RIIIb-NA2/NA2 and Fc gamma RIIIb-NA1/NA2 genotypes than in Fc gamma RIIIb-NA1/NA1 individuals (P &lt; 0.05), Fc gamma RIla-R/R131 individuals also exhibited higher recurrence rates, though the difference was not statistically significant (P = 0.06), These results suggest that the Fc gamma RIIIb-NA2 allotype represents a risk factor for recurrence of adult periodontitis.

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  • Loss of Fcγ receptor and impaired phagocytosis of polymorphonuclear leukocytes in gingival crevicular fluid 査読

    Akira Miyazaki, Tetsuo Kobayashi, Takashi Suzuki, Hiromasa Yoshie, Kohji Hara

    Journal of Periodontal Research   32 ( 5 )   439 - 446   1997年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    Immunoglobulin G type II and III receptors (Fc gamma RII and Fc gamma RIII) are essential for polymorphonuclear leukocytic (PMNs) phagocytosis. Our previous study demonstrated a downregulation of Fc gamma RIII on PMNs in gingival crevicular fluid (GCF). To determine whether this receptor downregulation may contribute to the periodontal host defence borne by PMNs, we examined the correlation between Fc gamma RII and Fc gamma RIII expressions and the phagocytic capacity of GCF-PMNs. In order to verify at which level of cellular events the loss of Fc gamma R occurs, we quantified mRNA levels to assess a de novo synthesis of these receptors. GCF was collected from 21 patients with adult periodontitis by gingival crevicular washing. Autologous peripheral blood (PB) PMNs served as control. Surface expressions of Fc gamma Rs and phagocytic capacity via Fc gamma Rs were analysed by flow cytometry. The difference in Fc gamma R mRNA levels between GCF- and PB-PMNs was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The amplified products were visualized by agarose gel electrophoresis and the endproduct yields were quantified by computerized image-analysis. Both Fc gamma RII and Fc gamma RIII expressions and phagocytic capacity on GCF-PMNs were significantly lower than those on PB-PMNs (p&lt;0.001). The downregulation of Fc gamma Rs on GCF-PMNs significantly correlated with the phagocytic capacity (r = 0.66 for Fc gamma RIII, p &lt; 0.01; r = 0.50 for Fc gamma RII, p &lt; 0.05). The mRNA level of Fc gamma RIII of GCF-PMNs was significantly lower than that of PB-PMNs (p &lt; 0.05). Thus, GCF-PMNs are characterized by the decreased surface expressions and mRNA levels of Fc gamma Rs, and the impaired phagocytosis.

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  • Changes in complement and immunoglobulin G receptor expression on neutrophils associated with Porphyromonas gingivalis-induced inhibition of phagocytosis 査読

    HIDEAKI TAI, TETSUO KOBAYASHI, KOHJI HARA

    Infection and Immunity   61 ( 8 )   3533 - 3535   1993年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC MICROBIOLOGY  

    We examined the phagocytic capacity and receptor expression on neutrophils stimulated with Porphyromonas gingivalis soluble products. Stimulated neutrophils had decreased phagocytic capacities and altered expression of CR1, CR3, FcgammaRII, and FcgammaRIII. For cases in which TLCK (N-alpha-p-tosyl-L-lysine chloromethyl ketone) neutralized the effects of the stimuli, the P. gingivalis-derived factors causing the phenomena seem to be trypsin-like proteases.

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  • The microbial flora from root canals and periodontal pockets of non-vital teeth associated with advanced periodontitis 査読

    Kobayashi T, Hayashi A, Yoshikawa R, Okuda K, Hara K

    International Endodontic Journal   23 ( 2 )   100 - 106   1990年3月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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▶ 全件表示

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  • 臨床歯周病学 第3版

    小林哲夫( 担当: 分担執筆 ,  範囲: 7章 遺伝的素因)

    医歯薬出版  2020年2月  ( ISBN:9784263458440

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    総ページ数:xi, 403p   記述言語:日本語

    CiNii Books

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  • ザ・ペリオドントロジー第3版

    小林哲夫( 担当: 分担執筆 ,  範囲: 第3章ペリオドンタルメディシン 8歯周病と関節リウマチ)

    永末書店  2019年2月 

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  • 膠原病と慢性炎症

    小林哲夫, 伊藤 聡, 村澤 章, 中園 清, 吉江弘正( 担当: 分担執筆 ,  範囲: 関節リウマチに及ぼす歯周病原菌感染由来タンパクシトルリン化の影響)

    北隆館  2016年8月 

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  • 歯周病と全身の健康

    吉江弘正, 小林哲夫, 栗原英見, 應原一久( 担当: 分担執筆 ,  範囲: 第1部 臨床研究からのエビデンス 4)歯周病と関節リウマチ)

    特定非営利活動法人 日本歯周病学会  2016年3月 

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  • 関節リウマチ治療中における感染症のマネジメント

    小林哲夫, 伊藤 聡, 中園 清, 村澤 章, 吉江弘正( 担当: 分担執筆 ,  範囲: 5章 病態別感染症 3)関節リウマチ患者における口腔ケア・歯周病治療の重要性)

    医薬ジャーナル社  2014年10月 

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  • ザ・ペリオドントロジー第2版

    小林哲夫( 担当: 分担執筆 ,  範囲: 第9章 ペリオドンタルメディシン 8.歯周病と関節リウマチ)

    永末書店  2014年3月 

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  • リウマチ看護パーフェクトマニュアル

    小林哲夫( 担当: 分担執筆 ,  範囲: 第4章 身につけたい看護技術 4. 口腔ケア)

    羊土社  2013年6月 

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  • イラストで語る歯科医学最前線

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 1. 歯周炎の遺伝子診断)

    クインテッセンス出版  2013年3月 

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  • 薬'12/'13 歯科 −疾患名から治療薬と処方例がすぐわかる本−

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 第7章 歯周疾患 歯周病の検査キット)

    クインテッセンス出版  2012年6月 

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  • ザ・ペリオドントロジー

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 第3章 検査、診断と治療 2 歯周疾患の検査 アドバンス編 歯周疾患の活動性)

    永末書店  2009年10月 

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  • Preventive Periodontology

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 第3章 Periodontal Medicine 19. 歯周炎と遺伝子)

    医歯薬出版  2007年5月 

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  • 歯周病と7つの病気

    小林哲夫( 担当: 分担執筆 ,  範囲: 第2章 7つの病気 7B.免疫・アレルギー疾患 関節リウマチ)

    永末書店  2007年3月 

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  • 臨床歯周病学

    小林哲夫( 担当: 分担執筆 ,  範囲: 第2編 ベーシック編 第6章 遺伝的素因)

    医歯薬出版  2007年3月 

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  • 歯周病と全身の健康を考える

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 第II章 歯周病のリスクファクターおよび全身疾患・全身状態との関連性 3.遺伝が歯周病に関わる仕組みは何処までわかっているか)

    医歯薬出版  2004年10月 

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  • 薬'06/'07 −口腔疾患からみる治療薬と処方例−

    小林哲夫, 田井秀明( 担当: 分担執筆 ,  範囲: 2.歯周疾患 慢性歯周炎)

    クインテッセンス出版  2004年10月 

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  • 歯周病治療のストラテジー

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: 第3編 ミレニアム歯周治療 第12章 ワクチン・サイトカイン・遺伝子治療)

    医歯薬出版  2002年7月 

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  • 先端医療シリーズ・歯科医学2 歯周病 −新しい治療を求めて−

    小林哲夫, 高井俊行, 吉江弘正( 担当: 分担執筆 ,  範囲: 第9章 歯周病の診断 第5節 Fcレセプター遺伝子型による歯周炎感受性診断)

    先端医療技術研究所  2000年8月 

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  • 歯周病のメインテナンス治療

    小林哲夫, 吉江弘正( 担当: 分担執筆 ,  範囲: メインテナンス時の再発に関連するリスクファクター −その検査法と対処法−)

    医歯薬出版  2000年5月 

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  • 歯周病診断のストラテジー

    吉江弘正, 小林哲夫( 担当: 分担執筆 ,  範囲: 第3編 予防・高齢社会のためのプロポーザル 1.歯周炎のリスク診断)

    医歯薬出版  1999年1月 

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  • かむこと、のむこと、たべること −咀嚼の科学−

    小林哲夫, 原 耕二( 担当: 分担執筆 ,  範囲: 5章 歯ぐきの病気/歯周病 1.歯周病の原因と診断)

    医歯薬出版  1996年9月 

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▶ 全件表示

MISC

  • 血清抗Porphyromonas gingivalis IgG抗体価と肝機能マーカー値の関連性-新潟県佐渡市における横断研究-

    高見澤圭, 杉田典子, 葭原明弘, 小林哲夫, 小林哲夫, 吉江弘正, 多部田康一

    日本歯周病学会会誌(Web)   61   2019年

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  • IgA receptor gene polymorphism in Japanese periodontitis patients.

    S. Kaneko, T. Kobayashi, K. Yamamoto, N. Sugita, H. Yoshie

    JOURNAL OF DENTAL RESEARCH   82   B362 - B362   2003年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Web of Science

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  • 慢性歯周炎罹患者の重症度とTNFレセプター2型遺伝子多型の関連性について

    島田 靖子, 田井 秀明, 遠藤 基弘, 小松 康高, 小林 哲夫, 山崎 和久, 吉江 弘正

    日本歯周病学会会誌   45   102 - 102   2003年4月

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  • Fcγレセプター遺伝子型は全身性エリテマトーデス及び侵襲性歯周炎の共通リスク因子である

    小林 哲夫, 山本 幸司, 杉田 典子, 安田 桂子, 金子 進, 吉江 弘正

    日本歯科保存学雑誌   45   58 - 58   2002年10月

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  • Analysis of TNF receptors Polymorphisms in Japanese patients with aggressive periodontitis.

    Y Shimada, H Tai, M Endo, T Kobayashi, K Yamazaki, H Yoshie

    JOURNAL OF DENTAL RESEARCH   81   A203 - A203   2002年3月

     詳細を見る

    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Web of Science

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  • Analysis of novel IL-1 polymorphisms in Japanese patients with aggressive periodontitis.

    H Tai, Y Shimada, E Go, K Orima, M Endo, Y Komatsu, T Kobayashi, K Yamazaki, H Yoshie

    JOURNAL OF DENTAL RESEARCH   81   A399 - A399   2002年3月

     詳細を見る

    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Web of Science

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  • Seven single nucleotide substitutions in human Fcg receptor IIB gene.

    N Sugita, K Yasuda, K Yamamoto, T Kobayashi, H Yoshie

    JOURNAL OF DENTAL RESEARCH   81   A313 - A313   2002年3月

     詳細を見る

    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R  

    Web of Science

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  • Differential gene expression in neutrophils from patients with generalized aggressive periodontitis

    Takehiko Kubota, Toshiya Morozumi, Kunihiko Shimizu, Noriko Sugita, Tetsuo Kobayashi, Hiromasa Yoshie

    Journal of Periodontal Research   36 ( 6 )   390 - 397   2001年

     詳細を見る

    記述言語:英語   出版者・発行元:Blackwell Munksgaard  

    Differential gene expression was investigated in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive-P, n = 6), generalized chronic periodontitis (Chronic-P. n = 6) and healthy controls (H, n = 8). Our results show that 37 genes were upregulated, while 27 genes were down-regulated in all Aggressive-P neutrophils by using RAP-PCR with 45 primer pairs. Reverse transcription-PCR analyses revealed that mRNA levels were significantly different (p &lt
    0.05) lor heat shock transcription factor 4b (HSF4b) gene, Kruppel-like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive-P compared to groups H and Chronic-P. Zf9 and muskelin genes were lower in Aggressive-P compared to the H groups, but no significant difference was noted compared to the Chronic-P group. The control genes, IL-1β and VEGF genes, were expressed at a significantly higher level in Aggressive-P and Chronic-P than H (p &lt
    0.01, p &lt
    0.05). In conclusion, the RAP-PCR technique used in this study enabled us to identify 3 Aggressive-P related genes, which had not been reported previously. Neutrophil functions in Aggressive-P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF-β) and muskelin (cellular adhesion).

    DOI: 10.1034/j.1600-0765.2001.360607.x

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講演・口頭発表等

  • オーラルケアとフレイル 招待

    小林 哲夫

    日本リウマチ学会中部支部学術集会 第31回中部リウマチ学会、 シンポジウムIII「関節リウマチとフレイル」  2019年9月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 関節リウマチ発症の環境要因としての歯周病 招待

    小林 哲夫

    第63回日本リウマチ学会総会・学術集会、シンポジウム20 生活習慣と関節リウマチ(環境要因)  2019年4月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 歯周炎が関節リウマチ発症に及ぼす影響 招待

    小林 哲夫

    特定非営利活動法人日本臨床歯周病学会第36回年次大会 「歯科医師セッション2」  2018年7月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 歯周病と関節リウマチ-現状と展望、歯科の役割- 招待

    小林 哲夫

    日本歯周病学会60周年記念京都大会 医科歯科連携シンポジウム2  2017年12月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 口腔内細菌と歯科治療に伴う菌血症 招待

    小林 哲夫

    第44回日本関節病学会 特別講演  2016年11月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • リウマチと歯周病 招待

    小林 哲夫

    平成26年度関東・甲信越地区リウマチ教育研修会  2014年11月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • Porphyromonas gingivalisによるタンパクシトルリン化と関節リウマチとの関連 招待

    小林 哲夫

    第56回歯科基礎医学会学術大会 サテライトシンポジウム  2014年9月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • リウマチと歯周病 招待

    小林 哲夫

    第21回新潟リウマチ医の会 教育講演  2014年1月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • 一生自分の歯で食べられるこどもに育てよう!~お口の中の病気と全身との関わりから~ 招待

    小林 哲夫

    新潟市歯科医師会西区主催 市民公開セミナー  2012年11月 

     詳細を見る

    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 歯周病予防の指導~学校と家庭の連携~ 招待

    小林 哲夫

    平成23年度阿賀町学校保健委員会講演会  2011年9月 

     詳細を見る

    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 日本人の歯周病感受性に関わる遺伝子多型 招待

    小林 哲夫

    第54回春季日本歯周病学会学術大会 シンポジウムI  2011年5月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 自己免疫疾患患者における歯周炎感受性遺伝子 招待

    小林 哲夫

    第51回春季日本歯周病学会学術大会 シンポジウムI  2008年4月 

     詳細を見る

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 関節リウマチと歯周病 招待

    小林 哲夫

    第14回新潟リウマチのケア研究会 特別講演  2007年3月 

     詳細を見る

    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • リウマチと歯周病 招待

    小林 哲夫

    第34回日本リウマチ・関節外科学会 市民公開講座  2006年11月 

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    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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  • 歯周炎感受性における免疫グロブリンFc受容体の遺伝子多型と機能の解析 招待

    小林 哲夫

    第49回春季日本歯周病学会学術大会、日本歯周病学会学術賞記念講演  2006年4月 

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    記述言語:日本語   会議種別:口頭発表(招待・特別)  

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  • Fcレセプターの遺伝子多型による歯周炎感受性診断 招待

    小林 哲夫

    第46回秋季日本歯周病学会学術大会 シンポジウム  2003年11月 

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    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 遺伝子多型と歯周病 招待

    小林 哲夫

    日本歯周病学会・第1回四国地区臨床研修会  2001年11月 

     詳細を見る

    記述言語:日本語   会議種別:公開講演,セミナー,チュートリアル,講習,講義等  

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受賞

  • 平成29年度日本歯科保存学会学術賞

    2017年6月  

    小林 哲夫

     詳細を見る

  • 第3回日本ラクトフェリン学会フォーラム賞

    2008年11月  

    小林 哲夫

     詳細を見る

  • 第5回日本歯周病学会学術賞

    2005年9月  

    小林 哲夫

     詳細を見る

共同研究・競争的資金等の研究

  • 歯周炎による関節リウマチ発症・悪化機序の解明-自己抗体の機能的糖鎖修飾の関与-

    研究課題/領域番号:21K09891  2021年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    代表者, 小林, 哲夫

      詳細を見る

    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

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  • 新たな歯周炎・リウマチ関連機序の解明-NET誘導性カルバミル化ペプチドの関与-

    2017年4月 - 2021年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

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    担当区分:研究代表者  資金種別:競争的資金

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  • 口腔細菌感染による関節リウマチの発症機序の解明

    2016年3月 - 2016年11月

    公益財団法人赤枝医学研究財団  平成27年度公益財団法人赤枝医学研究財団研究助成 

    代表者 小林哲夫

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    担当区分:研究代表者  資金種別:競争的資金

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  • リウマチ併発歯周炎患者のJAK分子標的・抗菌療法と機能検証

    2015年4月 - 2018年3月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究 

    代表者 吉江弘正, 分担者 小林哲夫

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    担当区分:研究分担者 

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  • シトルリン化プロファイルによる歯周炎とリウマチの共通発症メカニズムの解明

    2014年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

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    担当区分:研究代表者  資金種別:競争的資金

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  • 歯周炎・糖尿病・リウマチの共通リスクサイトカイン遺伝子の解明

    2013年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 基盤研究(A) 

    代表者 吉江弘正, 分担者, 小林哲夫

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    担当区分:研究分担者 

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  • 歯周炎病因論に基づくサイトカイン標的療法の確立

    2012年4月 - 2015年3月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究 

    代表者, 吉江弘正, 分担者 小林哲夫

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  • ゲノムメチル化プロファイルによる歯周炎とリウマチの共通発症機序の解明

    2010年4月 - 2014年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

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    担当区分:研究代表者  資金種別:競争的資金

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  • 歯周炎・リウマチにおけるIL-6エピジェネティクス病因論の確立

    2010年4月 - 2013年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B) 

    代表者, 吉江弘正, 分担者 小林哲夫

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  • 歯周炎感受性に関与するFcレセプター遺伝子と情報発現制御メカニズムの解析

    2007年4月 - 2010年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

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    担当区分:研究代表者  資金種別:競争的資金

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  • 歯周炎・膠原病のリスク遺伝子多型に基づくRNA発現とタンパク同定

    2007年4月 - 2010年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B) 

    代表者 吉江弘正,分担者 小林哲夫

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  • 免疫関連遺伝子多型を用いて口腔多発癌に有用な疾患感受性マーカーを探る

    2007年4月 - 2010年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    代表者, 藤田 一, 分担者 小林哲夫

      詳細を見る

  • 日本人歯周病患者の遺伝子多型に基づく感受性検査および診断の確立

    2004年4月 - 2007年3月

    日本学術振興会  科学研究費助成事業 基盤研究(A) 

    代表者, 永田俊彦, 分担者 小林哲夫

      詳細を見る

  • 遺伝子多型に基づく歯周炎カスタムメード療法の開発

    2004年4月 - 2007年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B) 

    代表者, 吉江弘正, 分担者 小林哲夫

      詳細を見る

  • ゲノムワイド関連解析を応用した歯周病感受性遺伝子検索システムの確立

    2004年4月 - 2007年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    代表者, 田井秀明, 分担者 小林哲夫

      詳細を見る

  • 歯周疾患と自己免疫疾患の共通リスク遺伝子の特定

    2003年4月 - 2006年3月

    日本学術振興会  科学研究費助成事業 基盤(B) 

    代表者 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周炎の遺伝子診断と免疫グロブリンA受容体ターゲッテイング療法の確立

    2001年4月 - 2004年3月

    日本学術振興会  科学研究費助成事業 基盤(B) 

    代表者 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周病検査の開発に関する総合的研究

    2001年4月 - 2003年3月

    日本学術振興会  科学研究費助成事業 基盤研究(A) 

    代表者, 河口浩之, 分担者 小林哲夫

      詳細を見る

  • 歯周病におけるFc受容体遺伝子診断と二極特異的抗体免疫療法の確立

    2000年4月 - 2003年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B) 

    代表者, 吉江弘正, 分担者 小林哲夫

      詳細を見る

  • 抑制性IgGレセプターによる免疫調節機能と歯周炎感受性との関連性

    2000年4月 - 2003年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C) 

    代表者 杉田典子,分担者 小林哲夫

      詳細を見る

  • 抗Fc受容体Bispecific抗体による難治性歯周炎免疫療法の開発

    2000年4月 - 2002年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周炎易感受性に関する特異的遺伝子の特定

    1998年4月 - 2001年3月

    日本学術振興会  科学研究費助成事業 基盤研究(B) 

    代表者, 吉江弘正, 分担者 小林哲夫

      詳細を見る

  • 早期発症型歯周炎における多形核白血球Fcレセプターフェノタイプの解析

    1996年4月 - 1998年3月

    日本学術振興会  科学研究費助成事業 基盤(C) 

    代表者 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周炎罹患局所における免疫生体防御ネットワーク機構の解明

    1995年4月 - 1998年3月

    日本学術振興会  科学研究費助成事業 基盤研究(A) 

    代表者 原 耕二, 分担者 小林哲夫

      詳細を見る

  • ポルフィロモナスジンジバリスによる歯肉溝滲出液好中球殺菌能の抑制機序の解析

    1995年4月 - 1996年3月

    日本学術振興会  科学研究費助成事業 奨励研究(A) 

    代表者, 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周炎患者の歯肉溝滲出液における多形核白血球殺菌能の動向

    1991年4月 - 1992年3月

    日本学術振興会  科学研究費助成事業 奨励研究(A) 

    代表者 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

  • 歯周炎患者多形核白血球のスーパーオキサイドおよびプロスタグランジンE2産生能

    1990年4月 - 1991年3月

    日本学術振興会  科学研究費助成事業 奨励研究(A) 

    代表者, 小林哲夫

      詳細を見る

    担当区分:研究代表者  資金種別:競争的資金

    researchmap

▶ 全件表示

 

担当経験のある授業科目

  • 歯周診断学演習ⅠA

    2017年
    -
    現在
    機関名:新潟大学

  • 歯周診断学演習ⅠB

    2017年
    -
    現在
    機関名:新潟大学

  • 早期臨床実習ⅡB

    2014年
    -
    現在
    機関名:新潟大学

  • 歯周病学実習

    2013年
    -
    現在
    機関名:新潟大学

  • 歯周診断学演習

    2009年
    -
    現在
    機関名:新潟大学

  • 臨床歯学コースワーク(歯周診断学コース)

    2009年
    -
    2011年
    機関名:新潟大学

  • 早期臨床実習IIB

    2005年
    -
    現在
    機関名:新潟大学

  • 早期臨床実習II

    2003年
    -
    2014年
    機関名:新潟大学

  • 歯周病学

    2002年
    -
    現在
    機関名:新潟大学

  • 早期臨床実習IB

    2002年
    -
    2011年
    機関名:新潟大学

  • 早期臨床実習I

    2002年
    -
    2011年
    機関名:新潟大学

▶ 全件表示

その他教育活動及び特記事項

  • 日本歯周病学会監修歯周病学基礎実習動画の活用調査

    2015年4月 - 2016年10月

  • webカメラを用いた術者視点動画教材作製の試み

    2009年4月 - 2010年7月

  • 研修歯科医の職業性ストレスに関するアンケート調査

    2007年4月 - 2008年7月

  • 「総合診療室型」卒後歯科臨床研修における経験量に影響を及ぼす因子

    2006年4月 - 2012年7月

  • 医歯学総合病院歯科医師臨床研修における研修歯科医による協力型施設の評価

    2006年4月 - 2011年7月

  • 新潟大学医歯学総合病院歯科医師臨床研修における複合型プログラム研修歯科医の評価

    2006年4月 - 2010年7月

  • 新潟大学医歯学総合病院歯科医師臨床研修における単独型プログラムの実際

    2006年4月 - 2009年11月

  • 歯科医師臨床研修における医療事故防止活動-危険予知トレーニングの試み—

    2006年4月 - 2009年7月

  • 新潟大学医歯学総合病院歯科における研修歯科医担当患者数の推移

    2006年4月 - 2008年8月

  • 歯科大学における総合診療研修プログラム-習熟度別の臨床研修の有効性について-

    2006年4月 - 2008年8月

  • 歯科医師臨床研修必修化に伴う病棟研修の充実に向けて

    2006年4月 - 2007年7月

  • 歯科医師臨床研修への保健所研修の導入

    2006年4月 - 2007年7月

  • 新潟大学医歯学総合病院歯科総合診療部の役割

    2006年4月 - 2007年7月

  • オンライン歯科臨床研修評価システム(DEBUT)の開発

    2005年4月 - 2007年7月

  • 新潟大学医歯学総合病院歯科における新歯科医師臨床研修制度に関する意識調査

    2005年4月 - 2006年6月

  • 情意領域評価としてのミニワークショップと面接の関連性

    2005年4月 - 2006年6月

  • 歯科医師臨床研修必修化に向けた新潟大学歯学部卒業生の動向

    2004年4月 - 2005年7月

  • 臨床研修歯科医適正評価としてのミニワークショップの検討

    2004年4月 - 2005年7月

  • 臨床予備実習への「臨床入門総合実習」の導入

    2002年4月 - 2003年7月

  • 新潟大学歯学部附属病院における卒後臨床研修の特徴

    2002年4月 - 2002年7月

  • 新入生カリキュラムへの早期臨床実習の導入とその効果

    2002年4月 - 2002年7月

▶ 全件表示