2024/12/21 更新

写真a

スギタ ノリコ
杉田 典子
SUGINO Noriko
所属
教育研究院 医歯学系 歯学系列 助教
医歯学総合研究科 口腔生命科学専攻 助教
歯学部 歯学科 助教
職名
助教
外部リンク

代表的な業績

    • 【論文】 Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors.  2006年5月

    • 【論文】 Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis.  2012年3月

    • 【論文】 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  2012年2月

学位

  • 博士(歯学) ( 1997年3月   新潟大学 )

研究キーワード

  • 歯周治療系歯学

研究分野

  • ライフサイエンス / 保存治療系歯学

経歴

  • 新潟大学   医歯学総合研究科 口腔生命科学専攻   助教

    2004年4月 - 現在

  • 新潟大学   歯学部 歯学科   助教

    2004年4月 - 現在

  • 新潟大学   歯学部附属病院   教務補佐員

    1997年10月 - 1999年3月

  • 新潟大学   歯学部附属病院   医員

    1989年4月 - 1997年9月

学歴

  • 新潟大学   Faculty of Dentistry

    - 1987年

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  • 新潟大学   歯学部

    - 1987年

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    国名: 日本国

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所属学協会

 

論文

  • UCP2 polymorphisms, daily step count, and number of teeth associated with all-cause mortality risk in Sado City: A hospital-based cohort study

    Han Lyu, Noriko Sugita, Shigeki Komatsu, Minako Wakasugi, Akio Yokoseki, Akihiro Yoshihara, Tetsuo Kobayashi, Kenji Sato, Hiroyuki Kawashima, Osamu Onodera, Ichiei Narita, Koichi Tabeta

    Heliyon   10 ( 12 )   e32512 - e32512   2024年6月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.heliyon.2024.e32512

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  • 佐渡総合病院外来患者における死亡率とUCP2遺伝子多型,歯数および歩数の関連性(UCP2 polymorphisms, teeth number and daily step count associated with mortality in Sado City)

    呂 かん, 杉田 典子, 葭原 明弘, 小林 哲夫, 多部田 康一

    日本歯周病学会会誌   65 ( 春季特別 )   135 - 135   2023年4月

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    記述言語:英語   出版者・発行元:(NPO)日本歯周病学会  

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

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

    Journal of Periodontal Research   2021年

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    掲載種別:研究論文(学術雑誌)  

    Objective: The aim of the present study was to evaluate the association between the periodontal and serological parameters and the disease activity of rheumatoid arthritis (RA) and between the anti-agalactosyl immunoglobulin G (IgG) titer and periodontitis severity. The objective was also to assess the effect of supragingival scaling on the serological parameters in patients with RA. Background: The periodontal and serological parameters in relation to the autoimmune inflammatory response have been linked to RA disease activity. However, the association of the anti-agalactosyl IgG titer with RA disease activity and periodontitis severity has not been elucidated. Methods: The periodontal, rheumatologic, and serological data were collected from 127 patients with RA in a retrospective cohort study. Of the 127 patients, 21 had been randomly assigned to receive oral hygiene instruction and supragingival scaling. The anti-agalactosyl IgG titer was determined by an electrochemiluminescence immunoassay. Results: The patients with a moderate to high RA disease activity showed significantly higher levels of probing depth (PD), clinical attachment level, anti-cyclic citrullinated peptide IgG, and anti-agalactosyl IgG titer and greater mean percentages of severe periodontitis than those with a low RA disease activity (p <.05 for all). Both univariate and multivariate analyses revealed a significantly positive correlation between the PD and RA disease activity (p =.009 and p =.001), between the anti-agalactosyl IgG titer and RA disease activity (p =.002 and p <.001), and between the anti-agalactosyl IgG titer and PD (p <.001 for both). Supragingival scaling significantly decreased the anti-agalactosyl IgG titer (p = 0.03). Conclusion: The PD and anti-agalactosyl IgG titer are positively interrelated, both of which are correlated positively with RA disease activity and influenced by supragingival scaling in patients with RA.

    DOI: 10.1111/jre.12867

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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. 国際誌

    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)  

    Background: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. Methods: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. Results: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. Conclusions: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

    DOI: 10.1016/j.heliyon.2020.e05531

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  • Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study. 国際誌

    Haruna Miyazawa, Takako Nakajima, Makoto Horimizu, Kazuhiro Okuda, Noriko Sugita, Kyoko Yamazaki, Lu Li, Yoshiko Hayashi-Okada, Takuya Arita, Misa Nishimoto, Mieko Nishida, Robert J Genco, Kazuhisa Yamazaki

    Dentistry journal   8 ( 4 )   2020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)  

    The aim of this study was to examine the effect of adjunct local minocycline administration on the microbiological parameters of subgingival plaque samples in the residual periodontal pockets. Ten chronic periodontitis patients under a supportive periodontal therapy regimen were recruited. After subgingival debridement, either 2% minocycline gel, Periocline™, (Test Group) or a placebo (Control Group) was administered to the selected sites once a week for three weeks. Subgingival plaque was collected at baseline, and at four weeks and eight weeks. The microbiological composition was analyzed by 16S ribosomal RNA sequencing. In the Test Group, α-diversity (evenness) decreased compared to the baseline (p = 0.005) and was lower compared to the control group at four weeks (p = 0.003). The microbial community composition between the two groups was significantly different at four weeks (p = 0.029). These changes were attributable to a decrease in the bacteria associated with periodontitis and an increase in the bacteria associated with periodontal health. Additionally, the improvement in bleeding on probing continued at eight weeks; however, there were little microbial effects of 2% minocycline gel observed at eight weeks. The control group demonstrated no change throughout the eight-week experimental period. Thus, local minocycline administration can change the subgingival microbial community of residual periodontal pockets.

    DOI: 10.3390/dj8040123

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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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  • 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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  • A polymorphism rs6815464 in the macrophage erythroblast attacher gene is associated with low bone mineral density in postmenopausal Japanese women. 査読 国際誌

    Yulan Che, Noriko Sugita, Akihiro Yoshihara, Masanori Iwasaki, Hideo Miyazaki, Kazutoshi Nakamura, Hiromasa Yoshie

    Gene   700   1 - 6   2019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)  

    BACKGROUND AND PURPOSES: Osteoporosis and osteopenia are multifactorial diseases characterized by low bone mineral density (BMD) and are susceptible to genetic and environmental risk factors. The macrophage erythroblast attacher (MAEA) was discovered as a protein to mediate the attachment of erythroid cells to macrophages and is essential for bone marrow hematopoiesis. MAEA is expressed in a wide range of cells and tissues including osteoblasts and osteoclasts. Recent studies have shown that a single nucleotide polymorphism (SNP) rs6815464 (C/G) in the MAEA gene increases the susceptibility of type 2 diabetes mellitus. However, the contribution of MAEA to bone metabolism remains unknown. Therefore, we performed this study to evaluate the association between MAEA polymorphism and low BMD. METHODS: In a cross-sectional study with postmenopausal Japanese women living in the Yokogoshi area, Niigata City, we evaluated whether rs6815464 was associated with low BMD. Blood samples were collected from 353 subjects (age 63.8 ± 5.4 years). The MAEA genotype was determined by TaqMan assay. BMD was assessed by dual-energy X-ray absorptiometry at the lumbar spine (L2-L4), hip and femoral neck. Low BMD was defined as a T-score <-1. RESULTS: The percentage of subjects with low BMD in the lumbar spine, total hip and femoral neck were 71%, 75% and 84% respectively. After adjusting age, BMI, HbA1c, smoking and alcohol consumption, the G-allele carriage was found to be associated with low BMD of total hip (odds ratio = 2.11, 95% CI: 1.14-3.91, P = 0.018), but not of the lumbar spine or femoral neck. CONCLUSION: The MAEA gene polymorphism rs6815464 was associated with low hip BMD in postmenopausal Japanese women.

    DOI: 10.1016/j.gene.2019.03.027

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  • MAEA rs6815464 polymorphism and periodontitis in postmenopausal Japanese females: A cross-sectional study. 査読 国際誌

    Yulan Che, Noriko Sugita, Akihiro Yoshihara, Masanori Iwasaki, Hideo Miyazaki, Kazutoshi Nakamura, Hiromasa Yoshie

    Archives of oral biology   102   128 - 134   2019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)  

    OBJECTIVES: Macrophage erythroblast attacher (MAEA) is a membrane protein that regulates the development of mature macrophages by mediating attachment with erythroblasts. A polymorphism rs6815464 (C/G) in MAEA gene was reported to be associated with type II diabetes. Along with diabetes, osteoporosis shows an increased prevalence in postmenopausal females, and both diseases have been reported to be associated with periodontitis. Therefore, we explored the relevance of the MAEA polymorphism to periodontitis, bone mineral density (BMD) and haemoglobin A1c (HbA1c). DESIGN: This was a cross-sectional study with the final sample comprised of 344 postmenopausal Japanese females. Probing pocket depth (PPD) and clinical attachment level (CAL) were measured. Genotype was determined by TaqMan assay. Blood biochemical parameters and BMD of the lumbar spine were evaluated. RESULTS: No differences were found in age, body mass index, HbA1c, BMD, number of teeth, bone metabolism parameters between the genotypes. Mean CAL and percentage of sites with PPD or CAL ≥ 5 mm were higher in the G-allele carriers than in the non-carriers. Multiple logistic regression analyses revealed that G-allele carriage was associated with severe periodontitis (odds ratio = 3.73, 95% CI = 1.36-10.19). CONCLUSION: Our results suggested that the MAEA gene polymorphism was independently associated with severe periodontitis.

    DOI: 10.1016/j.archoralbio.2019.04.008

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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12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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  • Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey 査読

    K. Tabeta, M. Hosojima, M. Nakajima, S. Miyauchi, H. Miyazawa, N. Takahashi, Y. Matsuda, N. Sugita, Y. Komatsu, K. Sato, T. Ishikawa, K. Akiishi, K. Yamazaki, K. Kato, A. Saito, H. Yoshie

    Journal of Periodontal Research   53 ( 3 )   446 - 456   2018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 and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross-sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high-sensitivity C-reactive protein [hs-CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin-6, tumor necrosis factor-α, soluble CD14, myeloperoxidase, matrix metalloproteinase-3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial-ankle aortic pulse wave velocity (PWV) index and the cardio-ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs-CRP were increased (P =.001 and.042, respectively), and the concentration of TBIL was decreased (P =.046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol and the concentrations of triglycerides, remnant-like particles-cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P =.038,.007,.002, and.049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β =.243, P =.040
    standardized β = −.443, P =.0002
    respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL.

    DOI: 10.1111/jre.12533

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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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  • 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

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    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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  • 塩酸ミノサイクリン局所投与がサポーティブペリオドンタルセラピー(SPT)期歯周炎患者の歯肉縁下細菌叢に及ぼす影響(第II報)

    宮沢 春菜, 中島 貴子, 堀水 慎, 杉田 典子, 奥田 一博, 山崎 和久, Li Lu, Genco Robert

    日本歯周病学会会誌   59 ( 秋季特別 )   190 - 190   2017年11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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  • 塩酸ミノサイクリン局所投与がサポーティブペリオドンタルセラピー(SPT)期歯周炎患者の歯肉縁下細菌叢に及ぼす影響(第I報)

    中島 貴子, 宮沢 春菜, 堀水 慎, 杉田 典子, 奥田 一博, 山崎 和久, Li Lu, Genco Robert

    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   147回   195 - 195   2017年10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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  • Relationship between renal function and periodontal disease in community-dwelling elderly women with different genotypes. 査読 国際誌

    Akihiro Yoshihara, Noriko Sugita, Masanori Iwasaki, Yanming Wang, Hideo Miyazaki, Hiromasa Yoshie, Kazutoshi Nakamura

    Journal of clinical periodontology   44 ( 5 )   484 - 489   2017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:WILEY  

    OBJECTIVES: The aim of this study was to examine the association between periodontal disease and renal function in elderly women with different genotypes. MATERIAL AND METHODS: A total of 332 postmenopausal never-smoking women were analysed. Poor renal function was defined as serum cystatin C > 0.91 mg/l. Periodontal disease markers such as periodontal inflamed surface area (PISA) were evaluated. Selected variables, including PISA quartile, body mass index (BMI), HbA1C and age in Arg allele carriers and non-carriers based on the beta-3 adrenergic receptor, or between Ala allele carriers and non-carriers based on peroxisome proliferator-activated receptor gamma, were analysed using multiple logistic regression analysis. RESULTS: The odds ratios of serum cystatin C level and PISA (fourth quartile) were significantly positive for both Arg (2.52; p = 0.035) and Ala allele non-carriers (2.36; p = 0.021). A significant association was also found between serum cystatin C level and BMI for both Arg (1.18; p = 0.001) and Ala allele non-carriers (1.12; p = 0.003). CONCLUSION: The results of this study suggest that periodontal inflammation might be associated with renal function. Furthermore, in both the Arg and Ala allele non-carriers, the associations between BMI and PISA for renal function became stronger.

    DOI: 10.1111/jcpe.12708

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  • PPARγ gene polymorphism, C-reactive protein level, BMI and periodontitis in post-menopausal Japanese women. 査読 国際誌

    Yangming Wang, Noriko Sugita, Akihiro Yoshihara, Masanori Iwasaki, Hideo Miyazaki, Kazutoshi Nakamura, Hiromasa Yoshie

    Gerodontology   33 ( 1 )   44 - 51   2016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)  

    BACKGROUND: Several studies have reported inconsistent results regarding the association between the PPARγPro12Ala polymorphism and obesity. Obese individuals had higher C-reactive protein (CRP) levels compared with those of normal weight, and PPARγ activation could significantly reduce serum high-sensitive CRP level. We have previously suggested that the Pro12Ala polymorphism represents a susceptibility factor for periodontitis, which is a known risk factor for increased CRP level. OBJECTIVES: The aim was to investigate associations between PPARγ gene polymorphism, serum CRP level, BMI and/or periodontitis among post-menopausal Japanese women. MATERIALS AND METHODS: The final sample in this study comprised 359 post-menopausal Japanese women. Periodontal parameters, including PD, CAL and BOP, were measured per tooth. PPARγPro12Ala genotype was determined by PCR-RFLP. Hs-CRP value was measured by a latex nephelometry assay. RESULTS: No significant differences in age, BMI or periodontal parameters were found between the genotypes. The percentages of sites with PD ≥ 4 mm were significantly higher among the hsCRP ≥ 1 mg/l group than the hsCRP < 1 mg/l group (p = 0.003). Positive correlations were found between serum hsCRP levels and the percentages of sites with PD ≥ 4 mm (p = 0.043) in PPARγ Ala allele carriers, and BMI (p = 0.033) in non-carriers. After adjustment for model covariates, BMI was significantly associated with serum hsCRP level. CONCLUSION: The PPARγPro12Ala polymorphism was not independently associated with periodontitis, serum CRP level or BMI in post-menopausal Japanese women. However, serum hsCRP level correlated with periodontitis in Ala allele carriers, and with BMI in non-carriers.

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  • The Interaction Between β-3 Adrenergic Receptor and Peroxisome Proliferator-Activated Receptor Gamma Gene Polymorphism to Periodontal Disease in Community-Dwelling Elderly Japanese. 査読 国際誌

    Akihiro Yoshihara, Noriko Sugita, Masanori Iwasaki, Yanming Wang, Hideo Miyazaki, Hiromasa Yoshie, Kazutoshi Nakamura

    Journal of periodontology   86 ( 8 )   955 - 63   2015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)  

    BACKGROUND: It has been hypothesized that β-3 adrenergic receptor and peroxisome proliferator-activated receptor gamma (PPARγ) might have gene-environmental and gene-gene interactions in periodontal disease. The purpose of this study is to elucidate the interaction between β-3 adrenergic receptor and PPARγ gene polymorphism with periodontal disease. METHODS: Three hundred thirty-two postmenopausal females were enrolled, and their serum high-sensitivity C-reactive protein (hsCRP) and hemoglobin A1c (HbA1c) were examined. β-3 adrenergic receptor and PPARγ genotypes were then determined. An oral examination was performed. The number of remaining teeth was counted, and the probing depth (PD) and clinical attachment level (CAL) were measured. Prevalence-rate ratios (PRRs) were calculated by multiple Poisson regression analyses to evaluate the relationship among periodontal disease markers, such as the number of sites with CAL 4 to 5 or ≥6 mm or PD 4 to 5 or ≥6 mm, and β-3 adrenergic receptor polymorphisms, PPARγ polymorphisms, and the interaction term adjusted by age, hsCRP, and HbA1c, after converting the number of remaining teeth (n) to an offset variable. RESULTS: In the participants with body mass index (BMI) ≥25, PRRs of β-3 adrenergic receptor genotype (Trp/Arg and Arg/Arg) for periodontal disease markers were 0.13 to 0.70 (P <0.0001 to 0.74), those of PPARγ genotype (Pro/Pro) were 0.66 to 3.14 (P = 0.01 to 0.68), and those of the interaction term for the two genotypes were 1.69 to 12.61 (P <0.0001 to 0.33). However, in the participants with BMI <25, a constant tendency was not observed. CONCLUSION: The results confirmed a positive relationship between the interaction term for β-3 adrenergic receptor genotype and PPARγ genotype and various periodontal markers in obese elderly females.

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  • Relationships between IL-6 gene polymorphism, low BMD and periodontitis in postmenopausal women 査読

    Y. Hanai, N. Sugita, Y. Wang, A. Yoshihara, M. Iwasaki, H. Miyazaki, K. Nakamura, H. Yoshie

    Archives of Oral Biology   60 ( 4 )   533 - 539   2015年

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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 Ltd  

    Objective IL-6 plays critical roles in bone resorption and the pathogenesis of periodontitis in both inflammation and alveolar bone loss. A negative correlation was observed between periodontitis and truncal bone mineral density (BMD) in postmenopausal women. The C allele carriers of a genetic polymorphism IL-6-572G/C have higher levels of serum IL-6 compared to G allele carriers. We investigated the possible effect of IL-6-572G/C polymorphism on the relationship between low BMD and periodontitis in postmenopausal women. Subjects and methods A total of 300 postmenopausal Japanese women who lived in Yokogoshi area of Niigata City, Japan, participated in this study. Genomic DNA was extracted from peripheral blood. The IL-6-572G/C genotypes were determined by the restriction fragment length polymorphism method. Bone mineral density (BMD) of right femoral neck and serum bone metabolism markers were measured. Low BMD was defined to have the BMD &lt
    80% of the mean for young adults. Periodontal parameters at two sites per tooth were measured. Results Serum osteocalcin levels were significantly lower in the IL-6-572G/G genotype (p = 0.025). In the -572G allele non-carriers, percentages of PPD ≥ 4 mm sites were significantly higher in low BMD group compared with the healthy control group (p = 0.021). Logistic regression analysis revealed low BMD to be associated with periodontitis (Odds ratio = 1.736, p = 0.027) after adjusted with IL-6-572G carriage, age, serum albumin level. Conclusions IL-6-572G/C polymorphism was not an independent risk factor of low BMD or periodontitis, but may affect the relationship between the two diseases in postmenopausal Japanese women.

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  • 歯周炎患者における塩酸クロルヘキシジンおよびCPC配合洗口液の抗菌作用 査読

    杉田典子, 中曽根直弘, 花井悠貴, 高橋昌之, 伊藤晴江, 両角俊哉, 久保田健彦, 奥田一博, 吉江弘正

    日本歯科保存学雑誌   57 ( 3 )   219 - 228   2014年6月

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    記述言語:日本語   出版者・発行元:The Japanese Society of Conservative Dentistry  

    目的 : 化学的プラークコントロール法としてグルコン酸クロルヘキシジン (CHG) 配合洗口液が効果的であるが, アレルギーなどの副作用が問題視されている. そこで今回, 塩酸クロルヘキシジン (CHH) と塩化セチルピリジニウム (CPC) を抗菌成分として配合した洗口液を開発し, 基本治療終了後の歯周炎患者が4週間使用した場合の口腔細菌に対する効果を評価した. <br> 材料と方法 : 新潟大学医歯学総合病院歯周病科を受診中で, 20歯以上を有し歯周基本治療後5mm以上の歯周ポケットを1~7部位有する歯周炎患者30名を対象とした. 新洗口液 (CHH+CPC群), CHG配合のコンクールF (CHG群), 抗菌成分を含まないコントロール洗口液 (コントロール群) を使用する3群にランダムに各10名を割付け, 二重盲検法で比較した. ベースラインおよび使用4週後に唾液・舌苔・歯肉縁上プラークを採取し, 総菌数, 総レンサ球菌数, <i>Porphyromonas gingivalis</i>および<i>Streptococcus mutans</i>の菌数を測定した. またterminal restriction fragment length polymorphism (T-RFLP) 法による解析を行った. <br> 成績 : いずれの洗口液でも有害事象は認められなかった. ベースライン (術前) と4週目を比較した結果, CHH+CPC群において唾液中総菌数と<i>S. mutans</i>数, 舌苔中総菌数, 縁上プラーク中総レンサ球菌数が有意に減少していた. CHG群においては, 縁上プラーク中総菌数の有意な減少が認められた. コントロール群では舌苔中総菌数および総レンサ球菌数が有意に減少していた. T-RFLP解析の結果, CHH+CPC群の唾液中において制限酵素<i>Msp I</i>切断断片から推定されるStreptococcus群, <i>Hha I</i>切断断片から推定されるStreptococcus・Eubacterium群, Parvimonas群およびPorphyromonas・Prevotella群が有意に減少していた. 縁上プラーク中の細菌については, <i>Hha I</i>切断断片から推定されるStreptococcus・Veillonella群がCHG群で有意に減少していた. その他に有意な変化は認められなかった. <br> 結論 : これらの結果より, CHH+CPC配合洗口液はより安全に使用でき, CHG配合洗口液と同程度以上の抗菌効果をもつことが示唆された.

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  • The interaction between beta-3 adrenergic receptor polymorphism and obesity to periodontal disease in community-dwelling elderly Japanese. 査読 国際誌

    Akihiro Yoshihara, Noriko Sugita, Masanori Iwasaki, Hideo Miyazaki, Kazutoshi Nakamura

    Journal of clinical periodontology   41 ( 5 )   460 - 6   2014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)  

    OBJECTIVES: The purpose of this study was to elucidate whether the association between beta-3 adrenergic receptor polymorphism and periodontal disease is modified by body weight. MATERIAL AND METHODS: We enrolled 332 postmenopausal women and determined their HbA1C levels (%) and beta-3 adrenergic receptor (rs4994) genotypes. Periodontal parameters including clinical attachment level (CAL) were measured. After selecting subjects for each body mass index (BMI) level, the prevalence rate ratio (PRR) by multiple Poisson regression analysis was calculated to evaluate the relationship between periodontal disease and beta-3 adrenergic receptor polymorphism. The number of sites with CAL≥6 mm was used as a dependent variable, and beta-3 adrenergic receptor genotype [categorized as Arg non-carriers (reference) or Arg carriers], age (y) and HbA1C (%) were adopted as independent variables. We converted the number of probing sites (n) to an offset variable. RESULTS: The PRR of the beta-3 adrenergic receptor genotype for the number of sites of CAL≥6 mm showed a positive association in subjects with BMI≥25.0 and increased markedly with BMI. The PRR in subjects with BMI≥30 was 3.10 (p < 0.0001). CONCLUSION: This study indicates a positive association between periodontal disease and the beta-3 adrenergic receptor genotype in obese individuals.

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  • Profiling biomarkers in gingival crevicular fluid using multiplex bead immunoassay. 査読 国際誌

    Yasuko Shimada, Koichi Tabeta, Noriko Sugita, Hiromasa Yoshie

    Archives of oral biology   58 ( 6 )   724 - 30   2013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:PERGAMON-ELSEVIER SCIENCE LTD  

    OBJECTIVE: Biomarkers in gingival crevicular fluid (GCF) have been investigated; however, measurements were limited by the small sample volume available. The aim of this study was to determine the levels of 40 different cytokines and chemokines in GCF samples. DESIGN: Eleven patients with generalised chronic periodontitis participating in a supportive periodontal therapy programme with remaining probing pocket depths (PDs) of >5mm were enrolled. One healthy and two diseased sites were sampled in each subject. Forty biomarkers in GCF were examined using a multiplex bead immunoassay. Porphyromonas gingivalis from the diseased sites was quantified by real-time polymerase chain reaction. RESULTS: Twenty-six biomarkers were detected in the GCF samples using the multiplex bead immunoassay. The levels of nine biomarkers were significantly different between the diseased and healthy sites after adjustment with Bonferroni's correction. The level of 26 biomarkers in diseased sites was compared between bleeding on probing (BOP)-positive and BOP-negative sites. Interleukin (IL)-1β and interferon-inducible protein (IP)-10 levels were significantly higher in BOP-positive diseased sites than BOP-negative diseased sites after adjustment for multiple comparisons (IL-1β, p=0.0007, IP-10; p=0.0009). In addition, the levels of IL-1β in GCF were found to be strongly correlated with the P. gingivalis ratio (r=0.646, p=0.0012). CONCLUSION: IL-1β levels in GCF correlate with the PDs, BOP and the presence of P. gingivalis in subgingival plaque. Multiplex bead assays can be useful in GCF studies. These findings can help in identifying new diagnostic methods in the diagnosis of periodontal disease.

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  • Peroxisome proliferator-activated receptor (PPAR) γ polymorphism, vitamin d, bone mineral density and periodontitis in postmenopausal women 査読

    Y. Wang, N. Sugita, A. Yoshihara, M. Iwasaki, H. Miyazaki, K. Nakamura, H. Yoshie

    Oral Diseases   19 ( 5 )   501 - 506   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: PPARg regulates bone metabolism and inflammation. Our previous study suggested PPARg Pro12Ala polymorphism to represent a susceptibility factor for periodontitis in pregnant Japanese women. Several recent papers have drawn attention to a possible link between low bone mineral density (BMD) and periodontitis in postmenopausal women. Since the pathogenesis for both involve bone remodeling, they might share common risk factors such as gene polymorphisms and vitamin D level. The present study investigated possible associations between the PPARgPro12Ala polymorphism, periodontitis, BMD and serum 25(OH)D in postmenopausal Japanese women. MATERIALS AND METHODS: PPARgPro12Ala genotypes of 359 women were determined by PCR-RFLP. BMD and periodontal parameters of each woman were measured. Serum 25(OH)D levels were determined by radioimmunoassay. RESULTS: PPARgPro12Ala polymorphism was not associated with periodontitis or BMD as an independent factor. Serum 25(OH)D was significantly higher in Ala allele carriers compared to non-carriers. Only in the Ala allele carriers, positive correlations were found between mean clinical attachment level and BMD, between BMD and 25(OH)D, and between percentage of sites with probing depth ≥4 mm and 25(OH)D. CONCLUSIONS: PPARgPro12Ala polymorphism was not independently associated with periodontitis or BMD. However, the polymorphism might be a modulator of the relationship between the two conditions in postmenopausal Japanese women.© 2012 John Wiley &amp
    Sons A/S.

    DOI: 10.1111/odi.12032

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  • 殺菌および抗炎症作用を有する歯磨剤ジェルコートFの歯周治療後残存歯周ポケットに対する効果

    岡田 崇之, 杉田 典子, 大塚 明美, 青木 由香, 高橋 昌之, 吉江 弘正

    日本歯科保存学雑誌   56 ( 4 )   344 - 352   2013年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本歯科保存学会  

    目的:歯周炎に対しスケーリング・ルートプレーニングを含む動的治療を行った後に残存したポケットに歯周病原細菌または炎症の継続が認められる場合,さらなる進行のリスクが高い.セルフケアとして,ブラッシングに薬剤を含む歯磨剤を併用し殺菌・消炎を図ることは,歯周炎の進行抑制に効果的と考えられる.歯磨剤ジェルコートFは,0.05%塩酸クロルヘキシジン,β-グリチルレチン酸,フッ化ナトリウム,ポリリン酸ナトリウムを含有している.今回,歯周治療後の残存歯周ポケットに対するジェルコートFの効果を調べた.材料と方法:対象は20歯以上を有する男女で,慢性歯周炎に対しスケーリング・ルートプレーニングを含む動的治療終了後1カ月以上経過し,2歯以上に6〜7mmの残存ポケットを有する20名とした.無作為化二重盲検法にて2群に分け実験群はジェルコートFを,コントロール群は塩酸クロルヘキシジン,β-グリチルレチン酸を除いたコントロール剤を使用した.残存ポケットを有する1歯を歯肉溝滲出液(GCF),ほかの1歯を細菌検査対象とし,GCF中のAST, ALT,縁下プラーク中のPorphyromonas gingivalis, Prevotella intermedia, Tannerella forsythiaおよびTreponema denticolaを測定した.歯周病検査を行った1週後(0w)にGCFと縁下プラークを採取し,次いでポケット内に歯磨剤を注入した.患者は毎日歯磨剤を使用してブラッシングを行い,就寝前にリテーナーにて歯磨剤を10分間適用した.4週後,同様の検査を行い結果を解析した.成績:実験群,コントロール群とも有害事象は認められなかった.ベースラインにおいて年齢,男女比,ポケット深さ,細菌レベル,GCF成分の差はなかった.術前術後比較では,実験群のみ対象歯のPlaque Index (PlI)とGingival Index (GI)が減少した.それ以外に有意な変化はなかった.また,術前術後の変化量に群間差はなかった.年齢・性別の影響を調整した線形回帰分析では,GIのみジェルコートFの効果が認められた.結論:リテーナーとブラッシングを併用してジェルコートFを4週間使用した結果,歯周治療後の残存ポケットの歯周病原細菌レベルおよび歯肉溝滲出液成分に有意な変化は認められなかった.しかし,臨床所見における縁上プラークおよび歯肉の炎症を減少させる可能性が示唆された.

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  • FcγRIIB-nt645+25A/G gene polymorphism and periodontitis in Japanese women with preeclampsia 査読

    Y. Wang, N. Sugita, A. Kikuchi, R. Iwanaga, E. Hirano, Y. Shimada, J. Sasahara, K. Tanaka, H. Yoshie

    International Journal of Immunogenetics   39 ( 6 )   492 - 500   2012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)  

    FcγRIIB contains a unique immunoreceptor tyrosine-based inhibition motif (ITIM) and functions as a negative feedback regulator of leucocyte activation and antibody production. We have previously reported FcγRIIB-nt645+25A/G gene polymorphism to be associated with prevalence and severity of periodontitis, FcγRIIB expression level on peripheral B lymphocytes and the serum IgG level against periodontopathic bacteria. Previous studies have reported maternal periodontal disease to be associated with an increased risk for preeclampsia. Therefore, FcγRIIB-nt645+25A/G gene polymorphism may be associated with preeclampsia by affecting immune response to periodontopathic bacteria in pregnant women. To elucidate whether FcγRIIB-nt645+25A/G gene polymorphism has associations with preeclampsia and/or periodontitis in pregnant Japanese women, a case-control study was carried out on women with preeclampsia (n=13) and without preeclampsia (n=106). Maternal periodontal parameters and bacterial data of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were collected within 5days of delivery. FcγR genotypes of each woman were determined using the genomic DNA isolated from peripheral blood. Serum IgG levels specific for each bacteria were determined. There was a significant association between FcγRIIB-nt645+25A/G polymorphism and preeclampsia (P=0.013). The frequency of the FcγRIIB-nt645+25AA genotype was higher in the preeclampsia group compared with the nonpreeclampsia group (P=0.007). The DNA level of A. actinomycetemcomitans from subgingival plaque was shown to be higher in the preeclampsia group (P=0.017). In conclusion, maternal FcγRIIB-nt645+25A/G polymorphism and subgingival DNA level of A. actinomycetemcomitans were significantly associated with the prevalence of preeclampsia in a limited number of Japanese women independently with periodontal infection. Further investigations should be performed to confirm this association in a larger population and to determine the biological process of the association. © 2012 Blackwell Publishing Ltd.

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

    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, FcγRIIA, FcγRIIB, FcγRIIIA, FcγRIIIB, and FcαR. 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 <33 years and FcαR(+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 FcαR(+56)T/C. In conclusion, there was no association between preterm birth and periodontitis in this study. A. actinomycetemcomitans, IL-6, and FcαR 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.

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  • The association of Aggregatibacter actinomycetemcomitans with preeclampsia in a subset of Japanese pregnant women. 査読 国際誌

    Emi Hirano, Noriko Sugita, Akira Kikuchi, Yasuko Shimada, Jun Sasahara, Ruriko Iwanaga, Kenichi Tanaka, Hiromasa Yoshie

    Journal of clinical periodontology   39 ( 3 )   229 - 38   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)  

    AIM: To determine whether periodontitis and three prominent members of the periodontal flora are associated with the development of preeclampsia (hypertension plus proteinuria) Materials and Methods: The samples were composed of 127 systemically healthy women. Within 5 days after labour, clinical periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were evaluated. Maternal serum IgG antibody specific for each bacteria was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was used to control for confounders (maternal age, body mass index before pregnancy, parity, and smoking). RESULTS: Eighteen women were affected with preeclampsia. The number of A.actinomycetemcomitans was shown to be significantly associated with preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence interval; 1.1–2.7). There were statistically significant differences between the preeclamptic and control groups in body mass index before pregnancy, pre-term birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We found no statistically significant association between preeclampsia and periodontal clinical parameters or the presence of periodontitis. CONCLUSION: In systemically healthy pregnant women, our findings suggested that the levels of maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic women.

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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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  • FcγRIIB polymorphisms, periodontitis and preterm birth in Japanese pregnant women 査読

    R. Iwanaga, N. Sugita, E. Hirano, J. Sasahara, A. Kikuchi, K. Tanaka, H. Yoshie

    Journal of Periodontal Research   46 ( 3 )   292 - 302   2011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)  

    Background and Objective: Recently, numerous studies have investigated the association of preterm birth with periodontitis. FcγRIIb is a human low-affinity receptor for immunoglobulin G (IgG). We have previously demonstrated single nucleotide polymorphisms (SNPs) of FcγRIIb to be associated with periodontitis and the serum-specific IgG level against periodontopathic bacteria. In this study, we investigated whether FcγRIIB gene polymorphisms were associated with periodontitis and/or pregnancy outcome. Material and Methods: We assessed the periodontal conditions of 122 Japanese pregnant women within 5d of delivery, and polymorphisms in FcγRIIB and in other Fcγ receptors were detected from the genomic DNA. Using clinical and genomic data, we analyzed the relationship between periodontitis, preterm birth and Fcγ receptor polymorphisms. Results: A significant difference was observed in the distribution of FcγRIIB-nt645+25A/G (rs2125685) between preterm and term birth groups, with a higher prevalence of nt645+25AA in the preterm birth group (p=0.032). Additionally, the FcγRIIB-nt645+25GG carrier showed significantly higher results for the prevalence of periodontitis (p=0.048), mean pocket depth (p=0.021), mean clinical attachment level (p=0.010), percentage of sites with pocket depth ≥4mm (p=0.005) and percentage of sites with clinical attachment level ≥3mm (p=0.007) than the AA carrier. An association between preterm birth and periodontitis was not observed in this study. Conclusion: These findings suggest that FcγRIIB-nt645+25AA carriers are more likely to experience preterm birth than FcγRIIB-nt645+25AG and GG carriers. Also, women with FcγRIIB-nt645+25G exhibited a greater tendency to have periodontitis than those with nt645+25A. © 2011 John Wiley &amp
    Sons A/S.

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  • The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. 査読 国際誌

    Yasuko Shimada, Yasutaka Komatsu, Ikuyo Ikezawa-Suzuki, Hideaki Tai, Noriko Sugita, Hiromasa Yoshie

    Journal of periodontology   81 ( 8 )   1118 - 23   2010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)  

    BACKGROUND: Previous studies suggest that periodontitis is closely related to obesity and metabolic syndrome. Leptin, a pleiotrophic hormone produced by adipose tissue, has been reported to be related to periodontitis. This study investigates the effects of periodontal treatment on the serum levels of leptin and other cytokines in patients with chronic periodontitis (CP). METHODS: Serum samples were taken from 33 CP patients (22 non-smokers, 11 smokers) and 18 healthy subjects. The serum leptin, adiponectin, tumor necrosis factor-alpha, interleukin (IL)-6, and C-reactive protein (CRP) levels were measured before and after non-surgical periodontal treatment. RESULTS: Significant differences between healthy and CP patients were found in serum leptin, IL-6, and CRP levels (P = 0.0018, P = 0.0064, and P = 0.0095, respectively). The serum leptin level was associated with mean probing depth, mean clinical attachment level, mean alveolar bone loss, and body mass index. There were significant associations between serum leptin levels and IL-6 and CRP levels. After non-surgical periodontal treatment, serum leptin, IL-6, and CRP levels were significantly decreased (mean +/- SD before and after, P value, respectively: leptin, 8.02 +/- 5.5, 7.10 +/- 4.4, P = 0.015; IL-6, 1.73 +/- 1.02, 1.36 +/- 0.73, P = 0.048; and CRP, 802.0 +/- 1065, 491.2 +/- 479.3, P = 0.047). CONCLUSIONS: Periodontal treatment is effective in reducing serum leptin, IL-6, and CRP levels. The results suggest that leptin, IL-6, and CRP could be mediating factors that connect metabolic syndrome and periodontitis.

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  • Peroxisome proliferator-activated receptor gamma polymorphism and periodontitis in pregnant Japanese women. 査読 国際誌

    Emi Hirano, Noriko Sugita, Akira Kikuchi, Yasuko Shimada, Jun Sasahara, Ruriko Iwanaga, Kenichi Tanaka, Hiromasa Yoshie

    Journal of periodontology   81 ( 6 )   897 - 906   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)  

    BACKGROUND: Recent studies suggest an association between maternal periodontitis and preterm birth, although the association remains controversial. It was suggested that mechanisms such as a genetic predisposition for a hyperinflammatory response cause periodontitis and preterm births. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor and ligand-dependent transcription factor. PPARgamma inhibits the transcriptional activity of the genes that produce proinflammatory mediators and repress periodontitis. Recently, a common polymorphism, proline(PRO)-to-alanine(ALA) mutation at codon12 in exonB (Pro12Ala: rs 1801282) PPARgamma, was reported to reduce the ability to transactivate responsive promoters. In this study, we tested whether the PPARgammaPro12Ala polymorphism was associated with maternal periodontitis and/or preterm birth. METHODS: Genomic DNA was isolated from the venous blood of pregnant Japanese women (term birth: n = 72; preterm birth: n = 58). The PPARgammaPro12Ala genotype was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Within 5 days after labor, clinical periodontal parameters were evaluated, and periodontopathic bacteria from the subgingival plaque were detected by species-specific PCR. RESULTS: The mean clinical attachment level (P = 0.012), mean probing depth (P = 0.031), mean gingival index (P = 0.037), and percentages of sites with bleeding on probing (P = 0.041) in women with the PPARgammaPro12Ala genotype were significantly higher than in women with the PPARgammaPro12Pro genotype. However, there was no association between preterm birth and periodontitis. CONCLUSION: We suggest that the PPARgammaPro12Ala polymorphism may represent a genetic susceptibility factor for the clinical measurements of periodontitis in a limited number of pregnant Japanese women, but it probably cannot influence the relationship between periodontitis and preterm birth.

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  • Antibody responses to Porphyromonas gingivalis outer membrane protein in the first trimester. 査読 国際誌

    Jun Sasahara, Akira Kikuchi, Koichi Takakuwa, Noriko Sugita, Yoshimitsu Abiko, Hiromasa Yoshie, Kenichi Tanaka

    The Australian & New Zealand journal of obstetrics & gynaecology   49 ( 2 )   137 - 41   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)  

    BACKGROUND: Porphyromonas gingivalis (Pg) is one of the most harmful periodontal pathogens and it has been reported that Pg is associated with preterm birth (PTB), intrauterine growth retardation (IUGR) and pregnancy-induced hypertension (PIH), discovered by animal experiments and clinical research. The relationship between adverse pregnancy outcomes and maternal antibody response to Pg is controversial. On the other hand, the serum C-reactive protein (CRP) has been recognised as a reliable serum marker of periodontal disease. AIMS: To determine the significance of antibody responses to Pg affecting pregnancy outcomes in the first trimester. METHODS: A case-control study was carried out on women with PTB (n = 58), IUGR (n = 91), PIH (n = 32) and without any complications (control, n = 98). The serum level of the CRP and IgG1 against 40-kDa outer membrane protein of Pg (anti-40-kDa OMP Pg-IgG1) in the first trimester was measured. RESULTS: The IUGR group, and PTB patients whose placentas were diagnosed as chorioamnionitis or whose vaginal flora included Lactobacilli, showed a lower level of anti-40-kDa OMP Pg-IgG1 than the control group. There was no difference in the serum CRP level between each case group and control group. CONCLUSIONS: These results suggest that a lack of humoral immunity against Pg in early pregnancy is associated with IUGR and some PTB.

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  • 歯周病原細菌に対する免疫調節に影響するFcγRIIb遺伝子多型と妊娠予後の関連性

    岩永 璃子, 平野 絵美, 杉田 典子, 吉江 弘正

    特定非営利活動法人 日本歯周病学会学術大会 プログラムおよび講演抄録集   2009   28 - 28   2009年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人 日本歯周病学会  

    DOI: 10.14833/amjsp.2009f.0.28.0

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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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  • The interleukin-1 and Fcgamma receptor gene polymorphisms in Japanese patients with rheumatoid arthritis and periodontitis. 査読 国際誌

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

    Journal of periodontology   78 ( 12 )   2311 - 8   2007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: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 (FcgammaR) play an important role. Functional polymorphisms of interleukin (IL)-1 and FcgammaR were shown to be associated with susceptibility to both diseases. Therefore, we evaluated whether the IL-1 and FcgammaR 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 FcgammaR genotypes (FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB) 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 <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 FcgammaR 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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  • The combined genotypes of stimulatory and inhibitory Fc gamma receptors associated with systemic lupus erythematosus and periodontitis in Japanese adults. 査読 国際誌

    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 - 74   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)  

    BACKGROUND: The pathobiology of systemic lupus erythematosus (SLE) is similar to that of periodontitis in that the immunoglobulin G Fc receptor (FcgammaR) and proinflammatory cytokines play an important role. Genetic variations of FcgammaR and interleukin (IL)-1 are associated with susceptibility to both diseases. Therefore, we evaluated whether the combination of FcgammaR 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 FcgammaR genotypes (FcgammaRIIA, FcgammaRIIB, FcgammaRIIIA, and FcgammaRIIIB) 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 R131 allele of stimulatory FcgammaRIIA and the 232T allele of inhibitory FcgammaRIIB was found in the SLE+P group compared to the H group (P = 0.01 and P = 0.0009, respectively). The combination of FcgammaRIIA-R131 and FcgammaRIIB-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 FcgammaR 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 FcgammaRIIA and inhibitory FcgammaRIIB genotypes may increase susceptibility to SLE and periodontitis in the Japanese population.

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  • Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors. 査読 国際誌

    Jiquan Zhang, Anna Raper, Noriko Sugita, Ravi Hingorani, Mariolina Salio, Michael J Palmowski, Vincenzo Cerundolo, Paul R Crocker

    Blood   107 ( 9 )   3600 - 8   2006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)  

    We describe the cloning and characterization of Siglec-H, a novel murine CD33-related siglec-like molecule with 2 immunoglobulin domains. Unlike other CD33-related siglecs, Siglec-H lacks tyrosine-based signaling motifs in its cytoplasmic tail. Although Siglec-H has the typical structural features required for sialic acid binding, no evidence for carbohydrate recognition was obtained. Specific monoclonal and polyclonal antibodies (Abs) were raised to Siglec-H and used to define its cellular expression pattern and functional properties. By flow cytometry, Siglec-H was expressed specifically on plasmacytoid dendritic cell (pDC) precursors in bone marrow, spleen, blood, and lymph nodes. Staining of tissue sections showed that Siglec-H was also expressed in a subset of marginal zone macrophages in the spleen and in medullary macrophages in lymph nodes. Using bone marrow-derived pDC precursors that express Siglec-H, addition of Abs did not influence cytokine production, either in the presence or absence of synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG). In comparison, Siglec-H functioned as an endocytic receptor and mediated efficient internalization of anti-Siglec-H Abs. By immunizing mice with ovalbumin-conjugated anti-Siglec-H Ab in the presence of CpG, we demonstrate generation of antigen-specific CD8 T cells in vivo. Targeting Siglec-H may therefore be a useful way of delivering antigens to pDC precursors for cross-presentation.

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  • FcγRIIIb genotypes and smoking in periodontal disease progression among community-dwelling older adults in Japanese 査読 国際誌

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

    J. Periodontol   76 ( 2 )   250 - 5   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)  

    DOI: 10.1902/jop.2005.76.2.250

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  • Alterations of gene expression in human neutrophils induced by smoking cessation. 査読 国際誌

    Toshiya Morozumi, Takehiko Kubota, Noriko Sugita, Manami Itagaki, Hiromasa Yoshie

    Journal of clinical periodontology   31 ( 12 )   1110 - 6   2004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)  

    OBJECTIVE: The purpose of the present study was to investigate the effect of smoking cessation on the peripheral neutrophil mRNA expression levels for inflammatory cytokines, chemokine, growth factor and matrix metalloproteinase (MMP). MATERIAL AND METHODS: Sixteen male smokers (aged 22-39 [25.3+/-4.0] years), with no clinical signs of periodontal and systemic diseases, were recruited. The experiment was performed before (baseline) and at 1, 4 and 8 weeks after smoking cessation. The status of smoking and smoking cessation was verified by exhaled carbon monoxide (CO) concentration and serum cotinine concentration. Neutrophils were isolated from each subjects' peripheral blood, then the cell was stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP). The mRNA expression levels for interleukin (IL)-1 beta, IL-8, tumor necrosis factor (TNF)-alpha, vascular endothelial growth factor (VEGF) and MMP-8 were analyzed by semiquantitative reverse transcription-polymerase chain reactions. The same experiment was performed on 11 non-smoking controls (four female and seven male), aged 23-27 (24.4+/-1.2) years. RESULTS: Eleven of 16 smokers successfully completed smoking cessation for 8 weeks. At 1 day after smoking cessation, there was a statistically significantly lower CO concentration than at baseline (p<0.01). Also, cotinine concentration markedly decreased at the second measurement, which was taken at 1 week. All of the analyzed mRNA expression levels of neutrophils from smokers were statistically significantly lower than that in non-smokers (p<0.01: IL-1 beta, IL-8, VEGF; p<0.05: TNF-alpha, MMP-8). The MMP-8 mRNA levels were statistically significantly increased at 8 weeks after smoking cessation compared with the baseline (p<0.05). Although the other mRNA expression levels were also elevated gradually from the baseline, they did not reach the statistically significant levels at 8 weeks after smoking cessation. CONCLUSION: The results showed that the neutrophil transcript levels in smokers were generally lower than those in non-smokers, which could be related to an impairment of neutrophils by smoking effects. The significant increase of MMP-8 mRNA levels were associated with the effects of smoking cessation, while recovery of the other mRNA levels seemed to require a bit longer period beyond 8 weeks after smoking cessation.

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  • Risk of periodontitis in systemic lupus erythematosus is associated with Fcgamma receptor polymorphisms. 査読 国際誌

    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 - 84   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 < 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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  • Differential gene expression in neutrophils from patients with generalized aggressive periodontitis 査読

    T Kubota, T Morozumi, K Shimizu, N Sugita, T Kobayashi, H Yoshie

    JOURNAL OF PERIODONTAL RESEARCH   36 ( 6 )   390 - 397   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:MUNKSGAARD INT PUBL LTD  

    Differential gene expression was investigated in neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine using RNA fingerprinting by arbitrarily pruned 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 transcript ion-PCR analyses revealed that mRNA levels were significantly different (p &lt; 0.05) for 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 I-I 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-1&lt;beta&gt; 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-beta) and muskelin (cellular adhesion).

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

    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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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with severity of CP. METHODS: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). FcγR genotypes for 3 bi-allelic polymorphisms (FcγRIIa-R/H131, FcγRIIIa-158V/F, FcγRIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions. RESULTS: There was a significant over-representation of FcγRIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, χ 2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and FcγR composite genotype comprising FcγRIIIa-158V plus FcγRIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, χ 2 = 9.35, P = 0.002; severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, χ 2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative; mean PD: 3.8 mm versus 3.2 mm, P = 0.005; mean CAL: 4.5 mm versus 3.7 mm, P = 0.005; mean % BL: 37.6% versus 29.9%, P = 0.008). CONCLUSION: Our results document the FcγRIIIa-158V allele and possibly FcγRIIIb-NA2 to be associated with severity of CP in Japanese patients. J Periodontol 2001;72:1324-1331.

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  • Analysis of vitamin D and Fcγ 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    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-Fcγ receptor IIIb (FcγRIIIb-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 FcγRIIIb 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 FcγRIIIb genotypes were determined by allele-specific polymerase chain-reactions. Our results indicated that frequencies of the VDR-B non-carrier and the FcγRIIIb-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-FcγRIIIb 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 FcγRIIIb genotype combination may be associated with susceptibility to G-EOP.

    DOI: 10.1177/00220345010800120501

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  • The Fcγ receptor genotype as a severity factor for chronic periodontitis in Japanese patients 査読

    T. Kobayashi, K. Yamamoto, N. Sugita, W. L. Van Der Pol, K. Yasuda, S. Kaneko, J. G.J. Van De Winkel, H. Yoshie

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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Functional polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) have been shown to be associated with generalized aggressive periodontitis (GAgP) or recurrence of chronic periodontitis (CP) in Japanese patients. The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with severity of CP. Methods: Fifty Japanese non-smoking patients with severe CP and 39 Japanese non-smoking patients with moderate CP were identified according to established clinical criteria, including measurements of probing depth (PD), clinical attachment level (CAL), and alveolar bone loss (BL). FcγR genotypes for 3 bi-allelic polymorphisms (FcγRIIa-R/H131, FcγRIIIa-158V/F, FcγRIIIb-NA1/NA2) were determined in these CP patients and 64 race-matched, non-smoking healthy controls by means of allele-specific polymerase chain reactions. Results: There was a significant over-representation of FcγRIIIa-158V allele in severe CP patients compared to moderate CP patients (odds ratio 2.03, 95% confidence interval [CI] 1.03-4.01, X2 = 4.86, P = 0.028). In addition, we found a strong association between CP severity and FcγR composite genotype comprising FcγRIIIa-158V plus FcγRIIIb-NA2 (severe CP versus moderate CP: odds ratio 4.69, 95% CI 1.52-15.10, X2 = 9.35, P = 0.002
    severe CP versus healthy controls: odds ratio 4.10, 95% CI 1.62-10.59, X2 = 11.13, P = 0.0009). Moreover, CP patients positive for the composite genotype exhibited more severe signs of periodontitis than composite genotype-negative individuals (positive versus negative
    mean PD: 3.8 mm versus 3.2 mm, P = 0.005
    mean CAL: 4.5 mm versus 3.7 mm, P = 0.005
    mean % BL: 37.6% versus 29.9%, P = 0.008). Conclusion: Our results document the FcγRIIIa-158V allele and possibly FcγRIIIb-NA2 to be associated with severity of CP in Japanese patients.

    DOI: 10.1902/jop.2001.72.10.1324

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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

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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:American Academy of Periodontology  

    Background: Genetic polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) were recently shown to be associated with recurrence rates of adult periodontitis (AP). The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with generalized early-onset periodontitis (G-EOP) in Japanese patients. Methods: Thirty-eight Japanese patients with G-EOP and 83 Japanese patients with AP were identified according to established clinical criteria, including measurements of probing depth, clinical attachment level, and alveolar bone level. FcγR genotypes for 3 bi-allelic polymorphisms were determined in these G-EOP and AP patients and 104 race-matched healthy controls by means of allele-specific polymerase chain reactions. Results: There was a significant difference in the distribution of FcγRIIIb genotypes between G-EOP patients and healthy controls (P = 0.02). Additionally, a significant over-representation of FcγRIIIb-NA2 allele was observed in G-EOP patients as compared to AP patients and controls (P = 0.02, P= 0.009, respectively). Moreover, we found a strong association between G-EOP and the composite genotype comprising FcγRIIIb-NA2 and FcγRIIIa-158F (G-EOP versus controls: odds ratio 2.4, 95% CI 1.0-6.0, χ2 = 4.13, P = 0.04). Conclusions: This study indicates that the FcγRIIIb-NA2 allele and possibly FcγRIIIa-158F could be associated with susceptibility to G-EOP in Japanese patients.

    DOI: 10.1902/jop.2000.71.9.1425

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  • Relevance of FcγRIIIa-158V/F polymorphism to recurrence of adult periodontitis in Japanese patients 査読

    Noriko Sugita, Kouii Yamamoto, Tetsuo Kobayashi, Hiromasa Yoshie, Kohji Hara, W.-Ludo Van Der Poi, Jan G.J. Van DE WINKEL, Tsuneyoshi Horigome

    Japanese Journal of Clinical Immunology   21   225 - 234   1998年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.2177/jsci.21.supplement_225

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  • PRESENCE OF ACTIVATED EOSINOPHILS, HIGH IGE AND SCD23 TITERS IN GINGIVAL CREVICULAR FLUID OF PATIENTS WITH ADULT PERIODONTITIS 査読

    T SUZUKI, N SUGITA, H YOSHIE, K HARA

    JOURNAL OF PERIODONTAL RESEARCH   30 ( 3 )   159 - 166   1995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:MUNKSGAARD INT PUBL LTD  

    Our previous studies showed that the expression of CD23 on polymorphonuclear leukocytes (PMNLs) in gingival crevicular fluid (GCF) from adult periodontitis (AP) patients was higher than in autologous peripheral blood (PB). Percentages of eosinophils in GCF PMNLs ranged between 6 and 14%. The purpose of the present studies was to increase understanding of the potential role of eosinophils and their products, including CD23, in periodontal disease. We analysed the eosinophil fraction in GCF and PB by flow cytometry using monoclonal antibodies to CD23b (BB10), eosinophil cationic protein (ECP) in stored and secretory forms (EG1 and EG2), and CD67 (80H3). Simultaneously, we measured IgE and soluble CD23 titer and GCF and serum by ELISA. Flow cytometric analysis of BB10, EG2 and 80H3 binding showed that GCF eosinophils from AP were activated. A large BB10(+) EG2(+) cellular fraction was detected in GCF from AP whereas it was very low in autologous serum (9.30+/-2.460 vs 0.16+/-0.10, p&lt;0.001). GCF from gingivitis patients exhibited no flow cytometric evidence for the presence of BB10(+) EG2(+) cells. BB10(+) EG1(+) cells, or inactivated eosinophils rated lower in GCF than in PB both in gingivitis and periodontitis patients (0.45+/-0.63 vs 1.83+/-0.96 and 0.15+/-0.30 vs 1.30+/-0.20, p&lt;0.05, respectively). IEE titer in AP patients reached 1208.1+/-421.2 IU/ml in GCF while only 49.1+/-50.4 in sera. Soluble CD23 in GCF reached 236.1+/-81.3 ng/ml in GCF and 5.6 +/- 1.8 ng/ml in sera. GCF of gingivitis patients, however, contained no detectable sCD23. Thus, GCF from AP patients displayed a high rate of activated eosinophils secreting ECP, while GCF of gingivitis patients did not. These results suggest that ECP-secreting activated eosinophils are relevant to the pathology of adult periodontitis.

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  • 歯周病原菌の酵素活性を指標とした迅速診断法(SK-013) : 臨床的特異性とSK-013のカットオフ値

    大竹 徹, 高野 都喜子, 栗原 千佳子, 南崎 信樹, 宮下 元, 長谷川 紘司, 杉田 典子, 佐藤 悦子, 田井 秀明, 小林 哲夫, 吉江 弘正, 原 耕二, 磯田 竜太朗, 河井 敬久, 佐保 輝之, 小郷 秀司, 三木 靖夫, 岡田 宏

    日本歯周病学会会誌   33 ( 1 )   154 - 163   1991年3月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人日本歯周病学会  

    歯周病原菌であるTreponema denticola, Bacteroides属らのペプチダーゼ活性を特異的かつ迅速(15分間)に測定可能な酵素活性測定キットSK-013を用いて歯周病検査薬としての臨床的特異性およびSK-013のカットオフ値について検索した。歯周炎,歯肉炎,う蝕,健常,歯周組織炎罹患歯の歯肉溝から採取したプラークを用いたSK-013活性を検索した結果,SK-013は歯周炎罹患歯に特異的な活性を示した。スピロヘータ数を基準にSK-013のカットオフ値を検討した結果,0.2Try U/mlが最も高い診断率を示した。さらに,段階的な標準色調を用いた肉眼判定を試みた結果,分光光度計で測定した値と高い一致率(Efficacy 93.3%)を得た。以上よりSK-013は,スピロヘータ数,歯周炎の有無を計測機器を用いなくても簡便にかつ迅速に行なえ,チェアーサイドでの有用性が高いことが示された。

    DOI: 10.2329/perio.33.154

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    その他リンク: http://search.jamas.or.jp/link/ui/1993025408

  • 歯周炎病原菌由来の酵素活性を指標とした迅速診断法(SK-013) : 歯周ポケット掻爬術の効果判定への応用

    杉田 典子, 佐藤 悦子, 田井 秀明, 小林 哲夫, 吉江 弘正, 原 耕二, 大竹 徹, 高野 都喜子, 栗原 千佳子, 南崎 信樹, 宮下 元, 長谷川 紘司, 磯田 竜太朗, 河井 敬久, 佐保 輝之, 小郷 秀司, 三木 靖夫, 岡田 宏

    日本歯周病学会会誌   33 ( 1 )   164 - 171   1991年3月

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    記述言語:日本語   出版者・発行元:特定非営利活動法人日本歯周病学会  

    本研究の目的は,歯周病原菌が特異的に産生するペプチダーゼ活性を迅速に測定できる検査薬SK-013 kitを用いて,歯周ポケット掻爬術の効果判定を行い,その有用性を評価することである。歯周炎患者64名のうち33名を歯周治療群(T群),31名を末治療群(NT群)に分け,1名につき1歯を被検歯として選択した。T群にはブラッシングによるプラークコントロール(初診時開始)および歯周ポケット掻爬術(プラークコントロール後4週目)を行いその効果を臨床診査並びにSK-013 kitによる酵素活性検査にて評価した(6,8,12週目)。NT群については,特に歯周治療は行わず初診時および12週目に臨床診査並びに酵素活性検査を行った。その結果,SK-013活性値は,プラークコントロールのみでは変化を示さなかったが,歯周ポケット掻爬術後,GI,PD,AL,BOPと共に著しく減少した。NT群のSK-013活性は,いずれの検査時においても有意な変化は認められなかった。これらの結果よりSK-013 kitによる酵素活性測定法は,歯周治療効果をモニタリングするのに非常に高い有用性があることが示された。

    DOI: 10.2329/perio.33.164

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  • Duration patterns of percussion sound in healthy and periodontally affected teeth 査読

    S. TAGUCHI, N. SUGITA, Y. ASAZUMA, K. HARA

    Journal of Oral Rehabilitation   17 ( 6 )   579 - 585   1990年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Ten periodontally affected subjects and 10 healthy subjects were selected in order to examine the duration patterns of percussion sounds in all upper teeth, excluding the 8′s. Probing depth, loss of attachment, tooth mobility by ‘Periotest’, bone loss and percussion sound duration via occlusal sound analyser were recorded during the pretreatment period. The following results were obtained from the study: the normal duration of percussion sounds ranged from 4.40–5.33 ms
    percussion sound values of periodontal patients were of longer duration than those of healthy subjects
    a close correlation between duration and other individual parameters was found in all upper teeth, with the exception of molars. Copyright © 1990, Wiley Blackwell. All rights reserved

    DOI: 10.1111/j.1365-2842.1990.tb01429.x

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  • 歯周病原菌の酵素活性を指標とした迅速診断法(SK‐013) 酵素活性と臨床所見,ポケット内細菌との関係:酵素活性と臨床所見, ポケット内細菌との関係

    大竹 徹, 桜井 千里, 栗原 千佳子, 南崎 信樹, 小林 誠, 宮下 元, 長谷川 紘司, 小林 哲夫, 佐藤 悦子, 杉田 典子, 奥田 一博, 柳村 光寛, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   32 ( 1 )   241 - 248   1990年

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

    歯周病原性が疑われている<I>Bacteroides</I>属, <I>Treponema denticola</I>等のペプチダーゼ活性を特異的かつ迅速に (15分間) 測定可能な酵素活性測定キットSK-013を用いてこの酵素活性と臨床所見, ポケット内細菌との関係を検索した。PD, GIなどの臨床診査指数および総菌数, Spirochete (S) 数, Motilerod (M) 数, M&S比と酵素活性は統計学的に有意に相関したがその相関係数はポケット内細菌との方が高い値を示した。また臨床担当医の総合的診断, Spirocheteの有無を基準としたSK-013のカットオフ値は0.2TryU/m<I>l</I>であり, その際の診断率はSensitivity: 92%, Efficacy: 96%と, 高い値を示した。これらのことからSK-013は, ポケット内細菌の多寡, Spirocheteの有無歯周炎の有無の診断を簡便にかつ迅速に行なえ, チェアーサイドでの有用性が高いことが示された。

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  • 歯周病原菌の酵素活性を指標とした迅速診断法(SK‐013) 歯周初期治療の効果判定への応用:歯周初期治療の効果判定への応用

    小林 哲夫, 佐藤 悦子, 杉田 典子, 奥田 一博, 柳村 光寛, 吉江 弘正, 原 耕二, 桜井 千里, 栗原 千佳子, 南崎 信樹, 大竹 徹, 小林 誠, 宮下 元, 長谷川 紘司

    日本歯周病学会会誌   32 ( 1 )   249 - 260   1990年

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

    本研究の目的は歯周初期治療の効果判定をより正確にかつ迅速に判定する方法としてSK-013kitによる酵素活性検査法が有用であるかどうかを評価することである。歯周炎罹患歯36歯に初期治療としてプラークコントロール (初診時), およびスケーリング, ルートプレーニング (4週目) を行い, その効果を臨床診査, 位相差顕微鏡による細菌検査, 並びにSK-013kitによる酵素活性検査を用いて評価した (6, 8, 12週目) 。プラークコントロー-ルでもスケーリングとルートプレーニングでも, いずれも細菌検査値, SK-013kit値は有意に減少したものの臨床所見で共通して有意に減少したのはProbingDepthのみであった。また, SK-013kit値と常時有意な相関が認められたのも細菌検査値のみであった。以上より初期治療効果を判定する際にSK-013kitによる酵素活性測定法は臨床的に非常に有用性の高い診断法であることが示された。

    DOI: 10.2329/perio.32.249

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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, 小林哲夫, 吉江弘正, 多部田康一

    新潟歯学会雑誌   50 ( 2 )   2020年

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  • β2-Microglobulin and Neutrophil Gelatinase-Associated Lipocalin, Potential Novel Urine Biomarkers in Periodontitis: A Cross-Sectional Study in Japanese. 査読 国際誌

    Mayuka Nakajima, Michihiro Hosojima, Koichi Tabeta, Sayuri Miyauchi, Miki Yamada-Hara, Naoki Takahashi, Haruna Miyazawa, Yumi Matsuda-Matsukawa, Keisuke Sato, Noriko Sugita, Yasutaka Komatsu, Tomomi Ishikawa, Kazuhiro Akiishi, Kazuhisa Yamazaki, Kiminori Kato, Akihiko Saito, Hiromasa Yoshie

    International journal of dentistry   2019   1394678 - 1394678   2019年

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    記述言語:英語  

    Objectives: Several serum biomarkers have been reported to increase in periodontitis patients as possible mediators linking periodontal inflammation to systemic diseases. However, the relationship between periodontitis and urine biomarkers is still unclear. The aim of this cross-sectional study was to investigate potential urine biomarkers of periodontitis in a Japanese population. Materials and Methods: This study included 108 male subjects, and microbiological and clinical parameters were evaluated as a periodontitis marker. The correlation between nine urine biomarkers (typically used to diagnose kidney disease) and periodontal parameters was analyzed. Based on the findings, β2-microglobulin (β2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) were selected for comparison and multivariate regression analysis, and the Kruskal-Wallis test followed by Bonferroni correction was used to identify differences in their concentrations between the three periodontitis groups (severe, moderate, and no/mild periodontitis). Results: β2-MG and NGAL exhibited a significant correlation with clinical parameters of periodontitis. The prevalence of clinical parameters such as bleeding on probing and number of sites with probing depth (PD) ≥ 6 mm were greater in the β2-MG high group (≥300 μg/g creatinine) than in the normal group (P=0.017 and 0.019, respectively). Multivariate regression analysis indicated that the number of sites with PD ≥ 6 mm was independently associated with urine β2-MG. Moreover, the number of sites with the clinical attachment level (CAL) ≥ 6 mm was greater in the NGAL high group (highest quartile) (P=0.041). Multivariate regression analysis showed that the number of sites with CAL ≥ 6 mm was associated independently with urine NGAL. Finally, β2-MG was significantly higher in the severe periodontitis subjects compared to the no/mild periodontitis subjects. Conclusion: The significant association between urine β2-MG or NGAL and periodontitis was revealed. These biomarkers can potentially be used to screen for or diagnose periodontitis. This trial is registered with the UMIN Clinical Trials Registry UMIN000013485.

    DOI: 10.1155/2019/1394678

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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, 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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  • 日本人成人において血中肝機能マーカー高値と歯槽骨吸収度との間に関連性は見られるか? 横断研究

    黒木 歩, 杉田 典子, 葭原 明弘, 小林 哲夫, 吉江 弘正, 若杉 三奈子, 横関 明男, 中村 和利, 成田 一衛, 遠藤 直人, 小松 繁樹, 百都 健, 佐藤 賢治

    新潟歯学会雑誌   47 ( 2 )   116 - 116   2017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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  • 歯周炎と血液・尿中バイオロジカルマーカーとの関連解析

    中島麻由佳, 中島麻由佳, 多部田康一, 宮内小百合, 杉田典子, 小松康高, 本田朋之, 高橋直紀, 宮澤春菜, 有松圭, 皆川高嘉, 松田由実, 松田由実, 佐藤圭祐, 佐藤圭祐, 山崎和久, 吉江弘正

    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(Web)   143rd   P126 (WEB ONLY) - 197   2015年11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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  • ホエイペプチド配合免疫調整流動食経口摂取が歯周炎患者における歯肉溝滲出液の炎症性サイトカインに与える影響

    久保田健彦, 冨田尊志, 濃野要, 阿部大輔, 清水太郎, 杉田典子, 金子昇, 根津新, 川島昭浩, 坪井洋, 佐々木一, 吉江弘正

    日本歯科保存学雑誌   58 ( 2 )   109 - 116   2015年4月

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  • ホエイペプチド配合流動食による歯周炎患者GCF中の炎症性サイトカインへ与える影響

    久保田健彦, 冨田尊志, 阿部大輔, 清水太郎, 濃野要, 金子昇, 杉田典子, 川島昭浩, 坪井洋, 佐々木一, 吉江弘正

    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(Web)   140th   P85 (WEB ONLY)   2014年6月

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  • 歯周炎患者における塩酸クロルヘキシジンおよびCPC配合洗口液の抗菌作用

    杉田典子, 中曽根直弘, 花井悠貴, 高橋昌之, 伊藤晴江, 両角俊哉, 久保田健彦, 奥田一博, 吉江弘正

    日本歯周病学会学術大会プログラムおよび講演抄録集   56th   121   2013年9月

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  • 6 関節リウマチと歯周炎の感受性に関連する遺伝子多型(I.一般演題,第8回新潟ゲノム医学研究会)

    小林 哲夫, 伊藤 聡, 黒田 毅, 山本 幸司, 杉田 典子, 成田 一衛, 住田 孝之, 下条 文武, 吉江 弘正

    新潟医学会雑誌   122 ( 12 )   692 - 692   2008年12月

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  • FcγRIIB遺伝子型と Porphyromonas gingivalis に対する抗体産生調節との関連性

    本間 祐子, 杉田 典子, 小林 哲夫, 安孫子 宜光, 吉江 弘正

    日本歯周病学会会誌   48   181 - 181   2006年3月

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  • 8 抑制性Fcγレセプター(FcγRIIB)遺伝子多型と歯周炎・SLE感受性との関連(I.一般演題,第5回新潟ゲノム医学研究会)

    小林 哲夫, 安田 桂子, 伊藤 聡, 杉田 典子, 黒田 毅, 山本 幸司, 成田 一衛, 下条 文武, 吉江 弘正

    新潟医学会雑誌   119 ( 11 )   697 - 697   2005年11月

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    その他リンク: http://search.jamas.or.jp/link/ui/2006106162

  • 4 FcγRIIB遺伝子多型と歯周炎感受性との関連性(第4回新潟ゲノム医学研究会)

    安田 桂子, 杉田 典子, 小林 哲夫, 山本 幸司, 吉江 弘正

    新潟医学会雑誌   118 ( 12 )   713 - 713   2004年12月

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  • Fc gamma RIIB gene polymorphisms in Japanese periodontitis patients

    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   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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  • 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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  • 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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  • D-11 FcγRIIB遺伝子型と侵襲性歯周炎との関連性

    安田 桂子, 杉田 典子, 山本 幸司, 小林 哲夫, 吉江 弘正

    日本歯周病学会会誌   44   144 - 144   2002年9月

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  • B-8-10 : 10 慢性歯周炎患者におけるFcγRIIB遺伝子多型の解析

    安田 桂子, 杉田 典子, 山本 幸司, 小林 哲夫, 吉江 弘正

    日本歯周病学会会誌   44   83 - 83   2002年3月

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  • B-10-10 : 30 全身性エリテマトーデス及び侵襲性歯周炎患者におけるFcγレセプター遺伝子多型の解析

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

    日本歯周病学会会誌   44   85 - 85   2002年3月

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  • B-9-10 : 20 日本人歯周炎患者におけるFcαレセプター遺伝子多型の解析

    金子 進, 山本 幸司, 小林 哲夫, 杉田 典子, 吉江 弘正

    日本歯周病学会会誌   44   84 - 84   2002年3月

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  • Fcg receptor polymorphisms in systemic lupus erythematosus and chronic periodontitis.

    K Yamamoto, T Kobayashi, S Ito, N Sugita, H Hasegawa, T Kuroda, S Kaneko, Narita, I, K Yasuda, M Nakano, F Gejyo, H Yoshie

    JOURNAL OF DENTAL RESEARCH   81   A368 - A368   2002年3月

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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

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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  

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

    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   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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  • 5)SLE・歯周炎感受性とFcγR遺伝子多型(一般演題, 新潟ゲノム医学研究会)

    杉田 典子, 小林 哲夫, 山本 幸司, 金子 進, 安田 桂子, 吉江 弘正, 伊藤 聡, 長谷川 尚, 黒田 毅, 成田 一衛, 中野 正明, 下条 文武

    新潟医学会雑誌   115 ( 10 )   544 - 544   2001年10月

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  • A-18-15 : 35 全身性エリテマトーデス及び歯周炎患者におけるFcγR遺伝子多型解析

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

    日本歯周病学会会誌   43   101 - 101   2001年9月

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

    T Kobayashi, K Yamamoto, N Sugita, AB van Spriel, S Kaneko, JGJ van de Winkel, H Yoshie

    INFECTION AND IMMUNITY   69 ( 5 )   2935 - 2942   2001年5月

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    記述言語:英語   出版者・発行元:AMER SOC MICROBIOLOGY  

    Porphyromonas gingivalis has been implicated as a causative pathogen in periodontitis. Immunotherapeutic approaches have recently been suggested to aid in the clearance of P, gingivalis from disease sites. Because antibody-Fe receptor (FeR) interactions play a role in the effector functions of polymorphonuclear neutrophils (PMN), we evaluated which FeR on PMN from gingival crevicular fluid (GCF) serves as an optimal target molecule for FcR-directed immunotherapy. GCF PMN and peripheral blood (PB) PMN from adult periodontitis patients were analyzed for their immunoglobulin G (IgG) and IgA FcR (Fc gammaR and Fc alphaR, respectively) expression and function by studying IgG- and IgA-mediated elimination of P. gingivalis. GCF PMN exhibited higher Fc alpha RI and Fc gamma RI levels and lower Fc gamma RIIa and Fc gamma RIIIb levels than PB PMN. Functional studies revealed that GCF PMN exhibited less of a capacity to phagocytose and kill IgG1-opsonized P. gingivalis than PB PMN. IgA1-mediated phagocytosis and killing capacity was, however, comparable between GCF PMN and PB PMN. In summary, these in vitro results document that Fc alpha RI represents a candidate target for FcR-directed immunotherapy for the clearance of P. gingivalis.

    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)

    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   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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  • B-27-16 : 20 早期発症型歯周炎患者の好中球における特異的mRNA発現

    両角 俊哉, 久保田 健彦, 清水 国彦, 杉田 典子, 小林 哲夫, 吉江 弘正

    日本歯周病学会会誌   43 ( 0 )   145 - 145   2001年3月

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  • A-6-10 : 00 Fcγレセプター遺伝子多型と成人性歯周炎重篤度との関連

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

    日本歯周病学会会誌   43   79 - 79   2001年3月

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

    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   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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  • Elevated mRNA expression for supervillin and vascular endothelial growth factor in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis

    Toshiya Morozumi, Takehiko Kubota, Noriko Sugita, Yutaka Ohsawa, Kazuhisa Yamazaki, Hiromasa Yoshie

    Journal of Periodontal Research   36 ( 3 )   160 - 168   2001年

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

    Differential gene expression was examined in human neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis (P. gingivalis-LPS) using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP-PCR). LPS from Escherichia coli (E. coli-LPS) was used as control. More than 200 differently expressed transcripts were found in 8 subjects showing differential regulation at the transcriptional level. Densitometric analyses revealed that 42-100 genes were upregulated, while 53-116 genes were downregulated by P. gingivalis-LPS compared with E. coli-LPS. The results of sequencing identification showed the presence of supervillin (SVIL) and vascular endothelial growth factor (VEGF) genes in the clones which were upregulated by P. gingivalis-LPS. Consequently, semiquantitative analyses proved that the level of mRNA for SVIL and VEGF were significantly higher in P. gingivalis-LPS-stimulated neutrophils than in other bacterial (E. coli, Actinobacillus actinomycetemcomitans, Prevotella intermedia) LPS- or synthetic lipid A-stimulated neutrophils. Our findings suggest that an elevated mRNA expression for SVIL could be associated with impaired function of neutrophils when stimulated by P. gingivalis-LPS. Further, the VEGF mRNA over-expression might be related to the pathogenesis of P. gingivalis-associated periodontitis. The RAP-PCR technique used in this study enabled us to identify a number of P. gingivalis-LPS regulated genes which hitherto have not been reported.

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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

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    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).

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  • C-28-10 : 20 Bispecific抗体による歯周炎免疫療法の開発 : 1.標的Fc受容体の選定

    小林 哲夫, 山本 幸司, 杉田 典子, 金子 進, 吉江 弘正

    日本歯周病学会会誌   42   165 - 165   2000年9月

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

    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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    記述言語:英語   出版者・発行元:AMER ACAD PERIODONTOLOGY  

    BACKGROUND: Genetic polymorphisms of immunoglobulin G (IgG) Fc receptors (FcγR) were recently shown to be associated with recurrence rates of adult periodontitis (AP). The purpose of this study was to evaluate whether FcγR polymorphisms are also associated with generalized early-onset periodontitis (G-EOP) in Japanese patients. METHODS: Thirty-eight Japanese patients with G-EOP and 83 Japanese patients with AP were identified according to established clinical criteria, including measurements of probing depth, clinical attachment level, and alveolar bone level. FcγR genotypes for 3 bi-allelic polymorphisms were determined in these G-EOP and AP patients and 104 race-matched healthy controls by means of allele-specific polymerase chain reactions. RESULTS: There was a significant difference in the distribution of FcγRIIIb genotypes between G-EOP patients and healthy controls (P = 0.02). Additionally, a significant over-representation of FcγRIIIb-NA2 allele was observed in G-EOP patients as compared to AP patients and controls (P = 0.02, P = 0.009, respectively). Moreover, we found a strong association between GEOP and the composite genotype comprising FcγRIIIb-NA2 and FcγRIIIa-158F (G-EOP versus controls: odds ratio 2.4, 95% CI 1.0-6.0, X2 = 4.13, P = 0.04). CONCLUSIONS: This study indicates that the FcγRIIIb-NA2 allele and possibly FcγRIIIa-158F could be associated with susceptibility to G-EOP in Japanese patients. J Periodontol 2000;71:1425-1432.

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  • A novel PCR-based method for direct Fc gamma receptor IIIa (CD163) allotyping

    FGJ Leppers-van de Straat, WL van der Pol, MD Jansen, N Sugita, H Yoshie, T Kobayashi, JGJ 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   出版者・発行元:ELSEVIER SCIENCE BV  

    Leukocyte IgG receptors (Fc gamma R) are important immune-response modulating molecules. Fc gamma RIIIa is expressed on macrophages, NK-cells and gamma delta-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 Fc gamma RIIIa genotypes are cumbersome. Therefore, we developed a novel, rapid and reliable PCR-based method to determine Fc gamma RIIIa genotypes. Comparison of genotyping results with direct Fc gamma RIIIa sequencing of 60 blood donors showed 100% accuracy of this new method. Since genotype frequencies of Fc gamma R polymorphisms depend strongly on race and ethnicity, we compared Fc gamma RIIIa 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 Fc gamma RIIa and Fc gamma RIIIb genotype frequencies (P&lt;0.001). (C) 2000 Elsevier Science B.V. All rights reserved.

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

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  • A-13-17 : 00 FcγRIIIb-NA1/NA2遺伝子多型からみた高齢者歯周炎抵抗性の解析

    杉田 典子, 小林 哲夫, 山本 幸司, 宮崎 秀夫, 吉江 弘正

    日本歯周病学会会誌   42   68 - 68   2000年4月

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  • A-12-16 : 50 FcγRIIIb細胞外領域での新たな変異(nt221A→G) : FcγRIIIbのN-linked glycosylation site数はリガンド親和性に影響を及ぼす

    山本 幸司, 杉田 典子, 小林 哲夫, 奥田 一博, 吉江 弘正

    日本歯周病学会会誌   42   67 - 67   2000年4月

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

    T Kobayashi, WL van der Pol, JGJ van de Winkel, K Hara, N Sugita, NAC Westerdaal, H Yoshie, T Horigome

    JOURNAL OF PERIODONTAL RESEARCH   35 ( 2 )   65 - 73   2000年4月

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    記述言語:英語   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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  • C-14-15 : 30 P.gingivalis-LPS刺激により誘導される好中球の特異的mRNA発現

    両角 俊哉, 久保田 健彦, 杉田 典子, 大澤 豊, 山崎 和久, 吉江 弘正

    日本歯周病学会会誌   41 ( 0 )   129 - 129   1999年9月

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  • A-12-11 : 00 早期発症型歯周炎患者におけるFcγレセプター遺伝子多型の解析

    小林 哲夫, 杉田 典子, Pol W-Ludo van der, 布川 寧子, Westerdaal Nomdo A.C., 山本 幸司, Winkel Jan G.J. van de, 吉江 弘正

    日本歯周病学会会誌   41   67 - 67   1999年9月

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

    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   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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  • A-27-14 : 10 Porphyromonas gingivalisに対するヒト末梢血好中球機能とFcγレセプターIIIb遺伝子多型との関連について

    小林 哲夫, van der Pol W-Ludo, 杉田 典子, Westerdaal Nomdo A.C., 吉江 弘正, 堀米 恒好, van de Winkel Jan G.J., 原 耕二

    日本歯周病学会会誌   41   84 - 84   1999年3月

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  • A-2-9 : 00 ヒト末梢血単核細胞FcγレセプターIIIAの遺伝子多型と成人性歯周炎再発との関連

    杉田 典子, 山本 幸司, 小林 哲夫, VAN DER POL W.-Ludo, 堀米 恒好, 吉江 弘正, VAN DE WINKEL Jan G.J., 原 耕二

    日本歯周病学会会誌   40   61 - 61   1998年9月

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  • Activation of transcription factors and IL-8 expression in neutrophils stimulated with lipopolysaccharide from Porphyromonas gingivalis

    N Sugita, A Kimura, Y Matsuki, T Yamamoto, H Yoshie, K Hara

    INFLAMMATION   22 ( 3 )   253 - 267   1998年6月

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    記述言語:英語   出版者・発行元:PLENUM PUBL CORP  

    DNA binding activity of NF-kappa B and AP-1 were examined in neutrophils stimulated with LPS purified from P. gingivalis, a major pathogenic bacteria of periodontitis lesion. Porphyromonas gingivalis LPS enhanced the activity reaching a peak at a concentration of 500 ng/ml in the absence of serum. The NF-kappa B activation stimulated with 10 ng/ml of P. gingivalis LPS was suppressed approximately 44% by treatment of neutrophils with anti-CD14 antibody under the presence of serum. Increase in the steady-state IL-8 mRNA level was concomitantly observed by stimulation of neutrophils with 500 ng/ml of P. gingivalis LPS under the absence of serum. These results indicate that P. gingivalis LPS activates NF-kappa B and AP-1 in both serum-dependent and -independent manners, followed by increased IL-8 transcription in neutrophils, and suggested a role for P. gingivalis LPS in IL-8 synthesis by neutrophils in inflamed gingiva and GCF.

    DOI: 10.1023/A:1022344031223

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  • C-37 Porphyromonas gingivalis-LPS刺激時の多形核白血球における転写因子とIL-8発現

    杉田 典子, 木村 麻子, 松木 裕, 山本 格, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   39   147 - 147   1997年3月

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  • C-31 歯肉溝滲出液-多形核白血球の貪食能に関するFc_γレセプター、補体レセプターの役割

    吉江 弘正, 宮崎 朗, 田井 秀明, 杉田 典子, 原 耕二

    日本歯周病学会会誌   39   141 - 141   1997年3月

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  • Characterization of complement receptor type 1 and type 3 mRNA expression on polymorphonuclear leucocytes (neutrophils) in gingival crevicular fluid from periodontitis-affected patients

    N Sugita, Y Matsuki, H Yoshie, K Hara

    ARCHIVES OF ORAL BIOLOGY   42 ( 2 )   113 - 120   1997年2月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    A previous study has demonstrated that complement receptors on the surface of polymerphonuclear leucocytes (neutrophils) in gingival crevicular fluid significantly increased compared with those in autologous peripheral blood obtained from periodontitis-affected subjects. The present study attempted to determine the mRNA levels of complement receptor types 1 and 3 (CR1, CR3) on neutrophils in gingival crevicular fluid using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Gingival crevicular fluid samples were obtained from 11 adult periodontitis patients by gingival crevicular washing, and venipunctured peripheral blood was used as a control. RT-PCR analysis was performed using the primer sets for CR1, CR3 and beta-actin. Digoxigenin-labelled RNA probes were synthesized from RT-PCR products for in situ hybridization. Both CR1 and CR3 mRNA levels relative to beta-actin were significantly lower in crevicular fluid neutrophils than in peripheral blood neutrophils (crevicular fluid-CR1: 32.75+/-22.93%, peripheral blood-CR1: 65.30+/-43.25%, p &lt;0.005; crevicular fluid-CR3: 9.09+/-5.34%, peripheral blood-CR3: 30.14+/-18.80%, p &lt;0.005). In in situ hybridization, a greater majority of neutrophils showed positive CR1 and CR3 mRNA expression, while only a few neutrophils showed positive signals in gingival crevicular fluid. Data in the present study suggest that increased expression of complement receptors on the neutrophil cell surface appears to be unrelated to de novo synthesis. (C) 1997 Elsevier Science Ltd.

    DOI: 10.1016/S0003-9969(96)00110-0

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  • 歯周疾患における免疫関与細胞の役割

    原 耕二, 杉田 典子, 青柳 敏彦, 須田 聡

    日本歯周病学会会誌   38 ( 3 )   243 - 260   1996年

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    記述言語:日本語   出版者・発行元:特定非営利活動法人日本歯周病学会  

    DOI: 10.2329/perio.38.243

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  • Decreased expression of CR1 and CR3 mRNA on PMNs in GCF

    N Sugita, Y Matsuki, T Suzuki, H Yoshie, K Hara

    JOURNAL OF DENTAL RESEARCH   75   685 - 685   1996年

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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:AMER ASSOC DENTAL RESEARCH  

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  • 歯周疾患における免疫関与細胞の役割(共著)

    原 耕二, 杉田 典子, 青柳 敏彦, 須田 聡

    日本歯周病学会誌   38 ( 3 )   243 - 260   1996年

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    DOI: 10.2329/perio.38.243

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  • B-32-9 : 20 歯肉溝滲出液中の多形核白血球補体レセプター(CR1,CR3)mRNA発現の解析

    杉田 典子, 松木 裕, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   37   122 - 122   1995年9月

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  • A-38 Porphyromonas gingivalisのGCF多形核白血球活性酸素産生能に及ぼす影響

    小林 哲夫, 田井 秀明, 杉田 典子, 原 耕二

    日本歯周病学会会誌   36   90 - 90   1994年3月

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  • DIFFERENTIAL EXPRESSION OF CR3, FC-EPSILON-RII AND FC-GAMMA-RIII ON POLYMORPHONUCLEAR LEUKOCYTES IN GINGIVAL CREVICULAR FLUID

    N SUGITA, T SUZUKI, H YOSHIE, N YOSHIDA, M ADACHI, K HARA

    JOURNAL OF PERIODONTAL RESEARCH   28 ( 5 )   363 - 372   1993年9月

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    記述言語:英語   出版者・発行元:MUNKSGAARD INT PUBL LTD  

    Polymorphonuclear leukocytes (PMNLs) are the most numerous cell population among the cellular infiltrates in gingival crevicular fluid (GCF) and play important roles in the host-defensive system in the gingival crevices. We determined the percentage of neutrophils, eosinophils and basophils in total PMNLs by light microscopic observation using Randolph-methylene blue staining, then assessed flow cytometric differences in the expression of CR3, FcgammaIII, FcepsilonRII, LFA-1alpha, and LFA-1beta on PMNL in GCF and peripheral blood (PB) from 21 patients with adult periodontitis (AP) and 13 healthy donors. Percentages of basophils and eosinophils were higher in GCF than in PB. In both AP patients and healthy subjects, expression of CR3 and FcepsilonRII was higher while FcgammaRIII was lower in GCF than in PB. The statistical analysis showed that the expressions of FcgammaRIII and FcepsilonRII on GCF PMNLs were lower in AP patients than in healthy subjects. Expressions of LFA-1alpha and beta on GCF were similar to those on PB PMNLs. PB PMNLs stimulated in vitro with Porphyromonas gingivalis culture supernatant and fMLP displayed an expression pattern of CR3, FcgammaRIII and FcepsilonRII on GCF PMNLs. However, C5a and IL-1 failed to induce changes in FcgammaRIII and FcepsilonRII. The results indicate that GCF neutrophils are activated, present enhanced adhesion and a decreased IgG-binding ability which would reflect that they are at the terminal stage of activation, and that GCF contains a larger eosinophil-fraction than in PB. Moreover, these GCF eosinophils appear to be activated.

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  • A-25-910 歯周炎患者におけるGCF中多形核白血球の各種表面レセプターと病態との関連性 : In vitroでの各種刺激による表面レセプター発現機序の検討

    杉田 典子, 大藤 泰人, 鈴木 卓, 吉江 弘正, 原 耕二, 吉田 尚子, 金谷 一司, 足立 正一

    日本歯周病学会会誌   33   98 - 98   1991年8月

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  • A-36-1100 歯周炎患者におけるGCF中多形核白血球の各種表面レセプターと病態との関連性

    杉田 典子, 大藤 泰人, 鈴木 卓, 吉江 弘正, 原 耕二, 平田 一郎, 金谷 一司, 吉田 尚子, 足立 正一

    日本歯周病学会会誌   33   119 - 119   1991年4月

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  • B-31-1125 歯周病原菌の酵素活性を指標とした迅速診断法(SK-013) : SK-013の診断率

    磯田 竜太朗, 河井 敬久, 佐保 輝之, 小郷 秀司, 三木 靖夫, 岡田 宏, 栗原 千佳子, 高野 都喜子, 南崎 信樹, 大竹 徹, 宮下 元, 長谷川 紘司, 杉田 典子, 佐藤 悦子, 田井 秀明, 小林 哲夫, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   32   125 - 125   1990年10月

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  • B-32-1135 歯周病原菌の酵素活性を指標とした迅速診断法(SK-013) : SK-013による歯周ポケット掻爬術の効果判定

    杉田 典子, 佐藤 悦子, 田井 秀明, 小林 哲夫, 吉江 弘正, 原 耕二, 栗原 千佳子, 高野 都喜子, 南崎 信樹, 大竹 徹, 宮下 元, 長谷川 紘司, 磯田 竜太朗, 河井 敬久, 佐保 輝之, 小郷 秀司, 三木 靖夫, 岡田 宏

    日本歯周病学会会誌   32   126 - 126   1990年10月

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  • B-30-1115 歯周病原菌の酵素活性を指標とした迅速診断法(SK-013) : SK-013の臨床的特異性

    栗原 千佳子, 高野 都喜子, 南崎 信樹, 大竹 徹, 宮下 元, 長谷川 紘司, 磯田 竜太朗, 河井 敬久, 佐保 輝之, 小郷 秀司, 三木 靖夫, 岡田 宏, 杉田 典子, 佐藤 悦子, 田井 秀明, 小林 哲夫, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   32   124 - 124   1990年10月

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  • A-25-1050 全部鋳造冠装着による咬合異常をもたらした場合の咬合音に及ぼす影響

    朝妻 八男, 袖山 敬央, 杉田 典子, 田口 智, 原 耕二, 渡辺 清志

    日本歯周病学会会誌   31   118 - 118   1989年9月

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  • B-19-940 歯周炎病原菌由来の酵素活性を指標とした迅速診断法(SK-013) : 4.診断能を示す指数の検討

    大竹 徹, 桜井 千里, 華岡 千佳子, 南崎 信樹, 小林 誠, 宮下 元, 長谷川 紘司, 小林 哲夫, 佐藤 悦子, 杉田 典子, 奥田 一博, 柳村 光寛, 吉江 弘正, 原 耕二

    日本歯周病学会会誌   31   127 - 127   1989年9月

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  • B-20-950 歯周炎病原菌由来の酵素活性を指標とした迅速診断法(SK-013) : 5.歯周初期治療の効果に対する判定

    小林 哲夫, 佐藤 悦子, 杉田 典子, 奥田 一博, 柳村 光寛, 吉江 弘正, 原 耕二, 桜井 千里, 華岡 千佳子, 南崎 信樹, 大竹 徹, 小林 誠, 宮下 元, 長谷川 紘司

    日本歯周病学会会誌   31   128 - 128   1989年9月

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  • B-49-14 : 50 咬合音診断器による歯周炎罹患歯の振動持続時間について : 打診振動をもたらした場合

    田口 智, 杉田 典子, 朝妻 八男, 原 耕二

    日本歯周病学会会誌   31   137 - 137   1989年4月

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  • 咬合音診断器による歯周炎罹患歯の打診音持続時間について

    田口 智, 杉田 典子, 朝妻 八男, 原 耕二

    下顎運動機能とEMG論文集   8   51 - 54   1989年

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    記述言語:日本語   出版者・発行元:日本顎口腔機能学会  

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▶ 全件表示

共同研究・競争的資金等の研究

  • 口腔および口蓋扁桃マイクロバイオームが慢性腎臓病に及ぼす包括的メカニズムの解明

    研究課題/領域番号:22K10337

    2022年4月 - 2025年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    葭原 明弘, 成田 一衛, 杉田 典子, 宮本 茜, 諏訪間 加奈, 新美 奏恵

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

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  • 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

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小林 哲夫, 杉田 典子

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

    本研究の目的は、歯周炎による関節リウマチ(RA)の発症・悪化機序を解明するため、RA患者の血清より免疫グロブリンG(IgG)自己抗体を抽出し、同自己抗体の糖鎖修飾発現についてプロファイリングを行い、同自己抗体糖鎖修飾の歯周炎・RA特異性について検証することである。
    本年度は第1段階として、インフォームド・コンセントが得られたRA患者127名を選定し、後ろ向きコホート研究として、歯周病検査、リウマチ検査、血液検査の結果を回収した。加えて、対象者の血清を対象に、ヒトガラクトース(Gal)欠損IgG 結合ビーズを固相とするルテニウム錯体標識レクチンを用いたサンドイッチ法による電気化学発光免疫測定法にてGal欠損IgG抗体価を測定した。
    その結果、中等度から高度のリウマチ疾患活動性のRA患者66名では、低疾患活動性のRA患者61名と比較して、プロービングデプス(PD)値、臨床的付着レベル、重度歯周炎頻度、およびシトルリン化蛋白・Gal欠損IgGに対する血清IgG抗体価が有意に高い値を示した。また、2変量・多変量解析の結果、PD値とリウマチ疾患活動性、ならびにGal欠損IgG血清抗体価とリウマチ疾患活動性との間に有意な正の相関を認めた。さらに、歯周病基本治療後では歯周病検査値とGal欠損IgG血清抗体価の有意な減少を認めた。
    以上の結果から、RA患者のPD値とGal欠損IgG血清抗体価は互いに正の相関関係にあり、これらの指標はリウマチ疾患活動性とも関連することが明らかになった。これらの結果は、RA患者の歯周炎が重症化するほどIgG自己抗体の糖鎖修飾が促進され、リウマチ疾患活動性を悪化させる可能性を示唆している。今後は、さらに対象数を追加して、他の予定解析指標についても検討していく必要がある。

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  • エネルギー代謝調節遺伝子UCPは握力と歯周炎および全身疾患の関連性に関与する

    研究課題/領域番号:21K09871

    2021年4月 - 2024年3月

    制度名:科学研究費助成事業

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子

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

    我々はこれまでに筋組織に多く存在し様々な疾患との関連が報告される脱共役タンパク(Uncoupling protein; UCP)について、歯周炎とUCP遺伝子多型の関連性を疫学研究で報告し、UCPによる歯周炎への関与を細胞実験にて明らかにしてきた。UCPの関与する筋力の指標である握力レベルと死因別死亡リスクとの関連性が久山スタディにて報告されている。そこで本研究では、UCP遺伝子多型と握力・全身疾患・歯周炎の関連性を疫学的に解析し、またその分子メカニズムを細胞実験、動物実験で検討することとした。
    2008年開始の臓器連関研究コホートプロジェクトであるPROST(Project in Sado for Total health)に参加した新潟県佐渡市佐渡総合病院の外来患者について歯科データおよび全身疾患を含む医科データと血液から採取したDNAを利用することにつき、新潟大学遺伝子倫理委員会に申請し承認を得た。このうち1750名についてはJaponica Arrayによる遺伝型解析済みであるため、それに含まれるUCP2遺伝子多型rs659366の遺伝型タイピング結果を利用することとし、同様に新潟大学遺伝子倫理委員会の承認を得た。しかしPROST参加者において現状では握力データを有する者が少なく、COVIC-19の影響下で新たに握力測定を追加できるペースは極めて遅くなっていることから、解析可能な人数が集まるまで長期的に待つ必要がある。一方でUCPは運動により発現が増強し、また運動習慣および歯数はそれぞれ死亡リスク低下に関連するとの報告があることから、運動習慣を表すデータとして1日平均歩数を用いて解析することにした。現在これらのデータを有するPROST参加者915名について歩数および歯数と死亡リスクおよび全身疾患との関連性、それに対するUCP2遺伝子多型の影響を解析中である。

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  • 歯周組織および口蓋扁桃の病態からみた慢性腎臓病に対する多角的発症メカニズムの解明

    研究課題/領域番号:18H03013

    2018年4月 - 2021年3月

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    葭原 明弘, 成田 一衛, 宮崎 秀夫, 杉田 典子

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    配分額:17160000円 ( 直接経費:13200000円 、 間接経費:3960000円 )

    地域疫学研究においては、新潟大学大学院医歯学総合研究科健康増進医学分野で実施されている「うおぬま地方の健康調査」メタボリックドミノ進展要因として食生活と身体活動の与える影響の解明を目的とした新潟県魚沼圏域住民/健診ベースのデータや生体試料を使用し、分析を行うこととした。2018年度、60歳代の男性で喫煙していない810人を対象にした。P.g.に対する血漿抗体価を測定し、歯周病の状態を表す指標とした。p.g.抗体価を3分位に分類した後分析を進めた。その結果、現在歯数とP.g.抗体価とはU字カーブ用の関連が認められた。同様に尿中クレアチニンや尿中尿素窒素ともU字カーブ用の関連が認められた。また、P.g.抗体価を従属変数、腎機能関連5項目を独立変数とし重回帰分析を実施したところ、クレアチニンクレアランスはP.g.抗体価と有意な関連が認められた(p=0.025)。一方、臨床疫学研究では、腎・膠原病内科、および歯周病科との打ち合わせが終了後、新潟大学の倫理審査委員会の承認を得た。その後、歯周組織および口蓋扁桃組織の細菌数の測定方法の確立を目指した。IgA腎症患者3例について口蓋扁桃組織における細菌数を測定したところ、全細菌数のうち、red complexの占める割合は0~3.47%であった。また、関連調査では、β3-adrenergic receptor genotypeと歯周病との関連をみると肥満者や喫煙経験が長い人の方がgenotypeの影響が強く出ていた。
    地域疫学研究におけるP.g.抗体価とU字用カーブを示す理由についてはさらに分析を進める必要がある。また、口蓋扁桃組織におけるred complexの占める割合は0~3.47%であったことについては分析の際に周囲の口蓋扁桃の生体組織が多く含まれている可能性が考えられた。今後さらに分析方法を検討する必要がある。

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  • エネルギー代謝調節遺伝子UCPの歯周炎における役割の解明

    研究課題/領域番号:18K09572

    2018年4月 - 2021年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    脱共役タンパク(Uncoupling protein; UCP)はミトコンドリア内膜に存在し、エネルギーを熱として放散させる機能を持つ。そのうちUCP2は白血球など広汎な組織に、UCP3は骨格筋、褐色脂肪組織、胸腺、脾臓に分布する。UCP遺伝子多型は糖尿病・肥満・骨粗鬆症に関連する。従来、歯周炎とこれらの疾患との関連性が報告されている。我々はこれまでに閉経後女性においてUCP2、UCP3遺伝型と重度歯周炎の関連性を示した。また細胞実験でUCPが活性酸素産生を抑制することを報告した。しかし対象とした集団に糖尿病・肥満・骨粗鬆症の有病者数が少なく、歯周炎とこれらの疾患との関係にUCP遺伝型が影響を与えているか否かを解析できなかった。
    そこで本研究は、総合病院外来患者である成人男女を対象に、歯周炎・糖尿病・肥満・骨粗鬆症とUCP遺伝型との関連を解析するとともに、歯周炎におけるUCP2、UCP3の役割について細胞実験および歯周炎モデルマウスを用いて明らかにすることを目的としている。
    初年度である平成30年度において、UCP遺伝型関連横断研究を行うため、佐渡市佐渡総合病院の外来患者を対象として既存のコホート研究PROST(Project in Sado for Total health)より、本研究に必要なデータと既に採取済みのDNAおよび血清サンプルについてプロジェクト管理者に使用許可申請を行った。
    一方、UCPの歯周炎における役割を解明するための細胞実験を行い、ヒトマクロファージ様細胞においてUCPが歯周病原細菌由来LPS刺激時の各種サイトカイン産生を抑制することを国際学会にて発表した。

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  • エネルギー代謝調節遺伝子UCPの閉経後女性歯周炎・糖尿病・肥満・骨粗鬆症への関与

    研究課題/領域番号:15K11384

    2015年4月 - 2018年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子, 中村 和利

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    配分額:4810000円 ( 直接経費:3700000円 、 間接経費:1110000円 )

    ミトコンドリア内膜の脱共役タンパク(Uncoupling protein; UCP)はエネルギーを熱へと変換させる。UCP1は脂肪組織に、UCP2は白血球に、UCP3は主に骨格筋に発現する。UCPは糖・脂質・骨代謝を制御し、炎症への関わりも示唆されてきた。そこで閉経後日本人女性を対象に歯周炎・糖尿病・肥満・骨粗鬆症とUCP遺伝型との関連性を検索し、歯周炎における役割を細胞実験で解析した。その結果、UCP2およびUCP3遺伝型は他の因子とは独立に重度歯周炎に関連性を示した。また白血球において歯周病原細菌による刺激時の活性酸素とサイトカイン産生はUCP2によって抑制されていることが明らかになった

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  • 歯周炎・肥満・骨粗鬆症関連遺伝子PPARガンマーの閉経後女性における解析

    研究課題/領域番号:24593121

    2012年4月 - 2015年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子, 中村 和利

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    配分額:5330000円 ( 直接経費:4100000円 、 間接経費:1230000円 )

    核内レセプターPPARガンマは炎症抑制・脂質・骨代謝調節機能を有する。従来PPARガンマ遺伝子多型と炎症・肥満・骨粗鬆症との関連が知られていた。閉経後女性ではこれらの疾患のリスクが増大する。そこでPPARガンマPro12Ala多型がこれらの疾患の共通リスクか否かを解明するため新潟市横越地区の閉経後女性359名を対象に肥満・骨粗鬆症・歯周炎の指標とPPARガンマ遺伝型との関連性を調べた。その結果、PPARガンマPro12Ala多型の Alaアレルは歯周炎と肥満・骨粗鬆症との関連を強めることが示唆された。この成果は疾患リスク診断に寄与しPPARガンマ制御が治療に役立つ可能性を示している。

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  • 核内レセプターPPARガンマー遺伝子多型の歯周炎・早産・肥満リスク

    研究課題/領域番号:21659480

    2009年 - 2011年

    制度名:科学研究費助成事業 挑戦的萌芽研究

    研究種目:挑戦的萌芽研究

    提供機関:日本学術振興会

    吉江 弘正, 杉田 典子, 菊池 朗

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    配分額:3180000円 ( 直接経費:3000000円 、 間接経費:180000円 )

    PPARガンマーは脂質代謝調節、炎症性サイトカイン産生抑制などの機能を持つ核内レセプターであり、活性を低下させる遺伝子多型Pro12Alaが報告されている。一方、近年歯周炎が早産や肥満に関与する可能性が報告されている。我々は妊婦においてPPARガンマー遺伝子多型と歯周炎、早産、肥満の関係を調べた。その結果、歯周炎と早産、肥満との間に関連性はなかったが、上記遺伝子多型と歯周炎に関連性が認められた。

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  • 早産への歯周炎の関与を解明する遺伝子学的研究

    研究課題/領域番号:19592385

    2007年 - 2008年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子, 菊池 朗, 菊池 朗

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    近年、妊婦の歯周病と早産の関連性が多く報告されているが、関連がないという報告もある。そこで本研究では、日本人妊婦で免疫や炎症に関わる遺伝子型22種と歯周炎および早産の関係を解析した。その結果、早産と歯周病あるいは遺伝子型の問に単独での関連性は見られなかったが、多変量ロジスティック回帰分析で歯周病と遺伝子型が関与するモデルが得られた。

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  • 歯周炎感受性に関与する抑制性IgGレセプターの免疫調節機能

    研究課題/領域番号:17592159

    2005年 - 2006年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    杉田 典子, 小林 哲夫

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    配分額:3300000円 ( 直接経費:3300000円 )

    1.FcγRIIb遺伝子型による歯周病原性細菌に対する抗体産生への調節機能
    ヒト抑制性IgGレセプターFCγRIIbは抗体産生の負の調節に必須である。私たちは以前の研究でFcγRIIB-1232T遺伝子型のFcγRIIB-232Tアレルが歯周炎と有意に関連していることを示した。そこで今回は、その機序を解明するため歯周病原性細菌Porphyromonas gingivalis(P.gingivalis)に対するIgG抗体産生がFcγRIIB-1232T遺伝子型によって異なるかどうかを調べた。歯周炎患者のゲノムDNAを用いてダイレクトシーケンシングにてFcγRIIB-1232T遺伝子型を決定した。また、血清中の総IgG濃度、P.gingivalis sonicateに対するIgG濃度、40-kDaリコンビナントP.gingivalis外膜蛋白(OMP)に対するIgGサブクラス濃度を調べた。その結果FcγRIIB-232Tアレル保有者は非保有者に比較してP.gingivalis 40-kDa OMPに対して有意に低いIgG2抗体濃度を示した。またFcγRIIB-232Tアレル保有者がP.gingivalis 40-kDa OMPに対して示した特異的IgGおよびIgG1レベルも非保有者に比較して低い傾向が認められた。この結果からFcγRIIB-232Tアレル保有者ではP.gingivalis外膜蛋白に対する抗体反応が低いことが歯周炎感受性に関与している可能性が示唆された。
    2.歯周炎患者における末梢血中のFcγRIIb発現
    歯周炎患者末梢血中における白血球上のFCγRIIb発現の量をフローサイトメトリーにて調べたところ、歯周炎患者末梢血中B細胞のFCγRIIb発現は、コントロールに比較して有意に低かった。

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  • 歯周疾患と自己免疫疾患の共通リスク遺伝子の特定

    研究課題/領域番号:15390644

    2003年 - 2005年

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    小林 哲夫, 杉田 典子, 山本 幸司, 伊藤 聡

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    配分額:14500000円 ( 直接経費:14500000円 )

    歯周疾患と自己免疫疾患に共通したリスク遺伝子を特定することを目的として、両疾患に共通する病因として、免疫複合体(自己抗体・細菌特異的抗体)の処理に重要な役割を担う免疫グロブリン受容体(FcR)と組織破壊に関与する炎症性サイトカインであるインターロイキン1(IL-1)遺伝子に着目し、遺伝子型解析とその機能的検証も実施した。
    その結果、
    1 慢性歯周炎患者213名、全身性エリテマトーデス(SLE)患者87名、健常者209名を対象に遺伝子多型を解析したところ、FcγRIIA遺伝子が歯周炎とSLEとに統計学的に有意な相関が認められた。この結果の機能的検証のため、FcγRIIA R/R131とFcγRIIA H/H131の各遺伝子型の単球・マクロファージの炎症性サイトカイン産生能を調べたところ、R/R131タイプで有意に高いIL-1産生能が認められ、FcγRIIA遺伝子は歯周炎とSLEとに共通したリスク遺伝子になる可能性が示唆された。
    2 抗体産生抑制性FcγRIIB遺伝子多型について、SLE患者66名、歯周疾患患者58名、健常者44名を対象に解析したところ、FcγRIIB nt775C/Tが共通リスク遺伝子であり、同多型は歯周病原菌Porphyromonas gingivalis 40kDa外膜蛋白に対する特異的抗体産生を制御することが認められた。
    3 関節リウマチ(RA)患者46名、慢性歯周炎患者140名、侵襲性歯周炎患者50名、健常者149名を対象に遺伝子多型解析したところ、IL-1B+3954遺伝子がRAの発症に関与することが示めされた。

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  • 歯周炎感受性に関与する骨代謝関連遺伝子の特定

    研究課題/領域番号:13470461

    2001年 - 2003年

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    吉江 弘正, 山崎 和久, 杉田 典子

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    配分額:16500000円 ( 直接経費:16500000円 )

    骨代謝に関連すると予想される候補遺伝子として、Vitamin D receptor (VDR),Tumor necrosis factor alpha (TNF-α),TNF receptor (TNFR),Interleukin-1(IL-1),IL-1 receptor antagonist (IL-IRA)およびCD14等を選択し、日本人においてこれらの遺伝子に存在する多型と侵襲性あるいは慢性歯周炎の発症との関連性について症例-対照研究を行った。遺伝子型の決定には末梢血から抽出したゲノムDNAを用いた。
    その結果、日本人においてTNF-α遺伝子の5'上流領域の多型は広汎型侵襲性歯周炎(G-AgP)の感受性に関与しないが、VDRとIgG受容体であるFcγRIIIbの遺伝子型とのコンビネーション、およびIL-1RA遺伝子に存在するVNTR(Variable number of tandem repeats)多型は、G-AgPの感受性に関与することが示唆された。また、TNFR 1のsingle nucleotide polymorphism (SNP,1塩基多型)とG-AgPおよびFcγRIIbのSNPとG-AgPとの関連性が示唆された。CD14遺伝子多型は歯周炎の発症に関与しないが、早期の疾患活動性に関与している可能性が示された。その他の多型については歯周炎患者と健常者で遺伝子型分布に有為な偏りがみられなかった。
    これらの解析結果により骨代謝に関連する多数の遺伝子が複合的に歯痛炎の発症に関与していると考えられる。本研究の成果は今後、多因子による歯周炎の総合的遺伝子診断として利用可能である。

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

    研究課題/領域番号:13557189

    2001年 - 2003年

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    小林 哲夫, 杉田 典子

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    配分額:11700000円 ( 直接経費:11700000円 )

    1 遺伝子診断:
    好中球特異的免疫グロブリンA受容体FcαRI(CD89)遺伝子やB細胞特異的免疫グロブリンG受容体FcγRIIB(CD32)遺伝子の塩基配列を解析したところFcαRIでは1カ所、FcγRIIBでは7カ所で新たな遺伝子多型が認められFcαRI nt 324 A/G、FcRIIB nt775 T/C遺伝子多型は侵襲性歯周炎と関連していることが判明した。また、FcαRI nt 324 A/G遺伝子多型はリガンド結合領域に存在するため、好中球機能を制御する可能性が考えられ、(歯周炎患者由来の末梢血並びた歯肉溝滲出液好中球の貪食能を解析したところ遺伝子型間で有意差が認められ、FcαRI nt 324 A/A遺伝子型患者は好中球貪食能の低下のために侵襲性歯周炎に対する感受性が高くなる可能性が示唆された。
    以上から、免疫グロブリンA受容体FcαRI遺伝子多型は歯周炎の感受性診断に有用であることが考えられる。
    2 ターゲッティング療法:
    歯周病原菌Porphyromonas gingivalisの特異抗体と免疫グロブリンA受容体FcαRI特異抗体より、それぞれBispecific抗体を遺伝子工学的に作製した。同抗体は末梢血好中球に対しては、コントロール抗体である抗P.gingivalis特異抗体とほぼ同程度のオプソニン活性が見られたが、歯肉溝滲出液好中球に対してはコントロール抗体と比べて有意に高いオプソニン活性が認められた。好中球上のFcαRI発現をフローサイトメトリーで解析したところ、末梢血好中球よりは歯肉溝滲出液好中球の方が有意に高い発現量が見られた。
    以上から、歯周ポケット内好中球のFcαRターゲッティング療法は有用であると考えられる

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  • 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

    研究課題/領域番号:12557191

    2000年 - 2002年

    制度名:科学研究費助成事業 基盤研究(B)

    研究種目:基盤研究(B)

    提供機関:日本学術振興会

    吉江 弘正, 杉田 典子, 小林 哲夫

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    配分額:10300000円 ( 直接経費:10300000円 )

    1 Fc受容体遺伝子診断:歯周炎重症度・抵抗性との関連、全身性疾患との関連、新たな遺伝子多型の発見慢性歯周炎(CP)の重症度とFc受容体(FcγR)遺伝子多型の関連性をアレル特異的PCR法にて検索したところ、中等度CP(39名)と比べ重度CP(50名)でFcγRIIIa-158Vアレルの頻度が有意に高かった。また、FcγRIIIa-158VとFcγRIIIb-NA2のアレル組合せとCP患者の重症度との間に強い相関が認められた。70歳高齢者599名を対象に歯周炎抵抗性との関連性も検索したところ、歯周炎感受性群(73名)と比べて歯周炎抵抗性群(46名)でFcγRIIIb-NA1アレルが有意に高頻度であることを認めた。さらに全身性エリテマトーデス(SLE)患者(60名)と歯周炎の関連性をFc受容体(FcγR)遺伝子多型を基に検討した結果、双方の疾患を有する患者はFcγRIIa-R131アレルの頻度が健常者に比較し有意に高かった。好中球特異的FcγRIIIB及びBリンパ球特異的FcγRIIBの遺伝子上塩基配列を解析したところ、前者で1カ所(nt221)、後者で7カ所(nt688,689,692,694,699,725+7,725+26)で遺伝子多型が認められた。
    2 免疫療法:抗P. gingivalisヒト特異的抗体の作製、その効果
    歯周病原菌P. gingivalisの40kDaリコンビナント外膜蛋白質(r40kDa OMP)を作製し同抗原をヒト抗体産生マウス(KMマウス)腹腔に接種・免疫し、抗r40kDa OMPヒト特異抗体を合計102クローン作製した。
    そのうちIgGは99クローンあり、サブクラスでは、IgG1が84クローン、IgG2が11クローン、IgG4が4クローンで、IgG3クローンは認められなかった。P. gingivalis r40kDa OMP・全菌体に対する結合能をELISA測定し、結合能の高い3クローンについて好中球の貪食活性を調べたところ、ポリクローナル抗体と比べて貪食能が著しく高かった。

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  • 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

    研究課題/領域番号:12672033

    2000年 - 2002年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小林 哲夫, 杉田 典子, 杉田 典子, 小林 哲夫

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    配分額:3300000円 ( 直接経費:3300000円 )

    FcγRIIBの免疫調節機能:
    抑制性IgGレセプターであるFcγRIIBの免疫調節機能を明らかにする一環としてFcγRIIB遺伝子を解析した。インフォームドコンセントが得られた健常者100名を対象に末梢血よりゲノムDNAを抽出し、ダイレクト・シークエンシングにて塩基配列を検索したところ、エクソン4において5カ所、イントロン4において2カ所、合計7カ所において1塩基置換を世界に先駆けて発見した。このうち、エクソン4でのnt 688、nt 694、nt 699の3カ所の1塩基置換はアミノ酸変異を伴っておりスプライシングとの関連が予想されたが、mRNAよりcDNAを抽出して調べたところ、関連は認められなかった。しかし、これらの1塩基置換はFcγRIIbのリガンド結合部位の構造に変化を生じさせている可能性が考えられる。
    FcγRIIB遺伝子多型と歯周炎感受性との関連性:
    上述した7カ所における遺伝子多型と最近報告されたFcγRIIBエクソン5での遺伝子多型について侵襲性歯周炎患者33名、慢性歯周炎患者73名、健常者71名を対象にインフォームドコンセントを得た後、末梢血を採取後ゲノムDNAを抽出し、各遺伝子型をダイレクトシークエンシングあるいはPCR法にて解析した。その結果、エクソン5の遺伝子多型nt 775 T/Cの分布が侵襲性歯周炎患者群と健常者群とで統計学的に有意に異なり、nt 775 Cの割合が侵襲性歯周炎患者群において有意に高かった(17% vs.6%、P=0.01、オッズ比3.4)。以上から、抑制性のIgGレセプターであるFcγRIIB遺伝子は歯周炎感受性を規定する因子になりうることが示唆された。

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

    研究課題/領域番号:12672032

    2000年 - 2001年

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    小林 哲夫, 杉田 典子

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    配分額:3100000円 ( 直接経費:3100000円 )

    インフォームド・コンセントを得た成人性歯周炎患者21名より歯肉溝滲出液(GCF)・末梢静脈血(PB)より好中球(PMN)を分離後にFcR発現を解析した結果、FcαR発現はPB-PMNに比べて、GCF-PMNで有意に増強していた。また、2種類のFcγR発現はGCF-PMNで有意な減少を示した。更に、FcγR・FcαRを介した殺菌効果を検索したところ、IgG1オプソニン化したPorphyromonas gingivalisに対する貪食・殺菌能は、PB-PMNの方がGCF-PMNと比べて高い一方、IgA1の場合は同等であった。以上から、歯周ポケットPMNの殺菌能賦活化にはFcαRが抗体の標的分子として確実性が高いと判断された。
    P.gingivalisを嫌気培養後、超音波破砕処理及びクロマトグラフィーにて、40kDaリコンビナント外膜蛋白質(r40kDa OMP)を作製した。同抗原をヒト抗体産生マウス(KMマウス)腹腔に接種・免疫し、脾細胞を回収した。マウス・ミエローマ細胞と融合後、抗r40kDa OMPヒト特異抗体が合計102クローン作製できた。そのうちIgGは99クローンあり、IgMが3クローンで、IgAクローンは作製できなかった。
    P.gingivalis r40kDa OMP及び、その全菌体に対するヒト特異抗体の結合能をELISA法により測定後、結合能の高いクローンについてP.gingivalisに対するPMN貪食能を調べた結果、ポリクローナル抗体と比べて有意に高く、歯周ポケットPMN貪食能賦活化においてヒト特異的抗体IgGでも有効である可能性が示唆された。

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  • Immunoglobulin receptors as genetic risk factors of periodontitis

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    資金種別:競争的資金

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  • 歯周炎感受性に関わるリスク遺伝子としてのイムノグロブリンレセプターの研究

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    資金種別:競争的資金

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