Updated on 2025/10/18

写真a

 
SUGINO Noriko
 
Organization
Academic Assembly Institute of Medicine and Dentistry SHIGAKU KEIRETU Assistant Professor
Graduate School of Medical and Dental Sciences Oral Life Science Assistant Professor
Faculty of Dentistry Department of Dentistry Assistant Professor
Title
Assistant Professor
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The Best Research Achievement in Research Career

    • 【Papers】 Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors.  2006.5

    • 【Papers】 Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis.  2012.3

    • 【Papers】 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  2012.2

Degree

  • 博士(歯学) ( 1997.3   新潟大学 )

Research Interests

  • 歯周治療系歯学

Research Areas

  • Life Science / Conservative dentistry

Research History

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science   Assistant Professor

    2004.4

  • Niigata University   Faculty of Dentistry School of Dentistry   Assistant Professor

    2004.4

  • Niigata University   Research Assistant

    2004.4 - 2007.3

  • Niigata University   Research Assistant

    2001.4 - 2004.3

  • Niigata University   Research Assistant

    1999.4 - 2001.3

  • Niigata University   University Dental Hospital

    1997.10 - 1999.3

  • Niigata University   University Dental Hospital

    1989.4 - 1997.9

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Education

  • Niigata University   Faculty of Dentistry

    - 1987

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  • Niigata University   Faculty of Dentistry

    - 1987

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    Country: Japan

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Professional Memberships

 

Papers

  • 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   2024.6

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    Publishing type:Research paper (scientific journal)   Publisher: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   2023.4

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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

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    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   2020.12

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    Language:Japanese   Publisher: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. International journal

    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   2020.11

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    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. International journal

    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 )   2020.10

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    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   2020.6

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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   2019.10

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  • A polymorphism rs6815464 in the macrophage erythroblast attacher gene is associated with low bone mineral density in postmenopausal Japanese women. Reviewed International journal

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

    Gene   700   1 - 6   2019.6

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    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. Reviewed International journal

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

    Archives of oral biology   102   128 - 134   2019.6

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    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. Reviewed International journal

    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   2018.12

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    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 Reviewed

    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   2018.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blackwell Munksgaard  

    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. Reviewed International journal

    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   2018.2

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    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. Reviewed International journal

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

    PloS one   13 ( 2 )   e0192365   2018

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    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   2017.11

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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   2017.10

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  • Relationship between renal function and periodontal disease in community-dwelling elderly women with different genotypes. Reviewed International journal

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

    Journal of clinical periodontology   44 ( 5 )   484 - 489   2017.5

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    DOI: 10.1111/jcpe.12708

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  • PPARγ gene polymorphism, C-reactive protein level, BMI and periodontitis in post-menopausal Japanese women. Reviewed International journal

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

    Gerodontology   33 ( 1 )   44 - 51   2016.3

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    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.

    DOI: 10.1111/ger.12110

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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. Reviewed International journal

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

    Journal of periodontology   86 ( 8 )   955 - 63   2015.8

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    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.

    DOI: 10.1902/jop.2015.140472

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

    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

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier Ltd  

    DOI: 10.1016/j.archoralbio.2014.12.005

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  • Microbiological Effects of a Low-concentration Chlorhexidine Hydrochloride/cetylpyridinium Chloride Mouth Rinse for Patients with Periodontitis Reviewed

    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   2014.6

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    Purpose: Mouth rinse with chlorhexidine gluconate (CHG) has been reported to be effective as a chemical plaque control. However, undesirable side effects such as allergy are known problems. Therefore, we developed a new mouth rinse formulated with both chlorhexidine hydrochloride (CHH) and cetylpyridinium chloride (CPC) as anti-microbial constituents and tested its effects on oral bacteria in patients with chronic periodontitis.<br> Methods: This was a short-term, randomized, controlled clinical trial. Systemically healthy 30 patients with ≥20 teeth were enrolled if they had 1 to 7 sites of residual pockets ≥5 mm after initial periodontal therapy with scaling and root planing. Patients were assigned to three groups and used placebo (control group), or rinse with 0.05% CHG (CHG group), or rinse with 0.05% CHH and 0.05% CPC (CHH+CPC group), for 4 weeks. In each patient, saliva, tongue coating and supragingival plaque were collected and microbiological parameters were measured with real-time PCR. Terminal restriction fragment length polymorphism (T-RFLP) analyses were also performed.<br> Results: No adverse event was observed. At the baseline, no difference was found in age, sex, number of teeth, or clinical periodontal parameters between the groups. Comparing the data at baseline and after 4 weeks, total bacterial counts and <i>S. mutans</i> in saliva, total bacterial counts in tongue coating and total streptococci in supragingival plaque were significantly decreased in the CHH+CPC group. In the CHG group, total bacterial counts in supragingival plaque were significantly decreased. Significant decreases of total bacterial counts and streptococci in tongue coating were detected in the control group. As the results from T-RFLP analyses, saliva from the CHH+CPC group showed significant reductions of presumed numbers of Streptococcus group in the digested fragments by <i>Msp I</i>, and Streptococcus, Eubacterium group, Parvimonas group and Porphyromonas, Prevotella group in the digested fragments by <i>Hha I</i>. Additionally, in supragingival plaque obtained from the CHG group after 4 weeks, presumed Streptococcus, Veillonella group from <i>Hha I</i> digests were significantly reduced. No change was observed between baseline and after 4 weeks in the other bacterial data.<br> Conclusion: The new mouth rinse formulated with CHH and CPC might be used safely and have equal to greater effects reducing oral bacteria than existing mouth rinse formulated with CHG alone.

    DOI: 10.11471/shikahozon.57.219

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  • The interaction between beta-3 adrenergic receptor polymorphism and obesity to periodontal disease in community-dwelling elderly Japanese. Reviewed International journal

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

    Journal of clinical periodontology   41 ( 5 )   460 - 6   2014.5

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    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. Reviewed International journal

    Yasuko Shimada, Koichi Tabeta, Noriko Sugita, Hiromasa Yoshie

    Archives of oral biology   58 ( 6 )   724 - 30   2013.6

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    DOI: 10.1016/j.archoralbio.2012.11.012

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

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

    Oral Diseases   19 ( 5 )   501 - 506   2013

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    DOI: 10.1111/odi.12032

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  • Effects of the Tooth Gel "Jellcoat F" on Residual Periodontal Pockets after Periodontal Therapy

    OKADA Takayuki, SUGITA Noriko, OTSUKA Akemi, AOKI Yuka, TAKAHASHI Masayuki, YOSHIE Hiromasa

    The Japanese Journal of Conservative Dentistry   56 ( 4 )   344 - 352   2013

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    Purpose: Periodontopathic bacteria and inflammation in a residual periodontal pocket after periodontal therapy increase the risk for further progression of periodontitis. A tooth cleaning gel containing antibacterial and anti-inflammatory agents would be effective to inhibit such progression. The tooth cleaning gel 'Jellcoat F' contains 0.05% chlorhexidine hydrochloride as an antibacterial and β-glycyrrhetinic acid as an anti-inflammatory. We evaluated the effects of Jellcoat F on residual periodontal pockets with clinical, microbiological and biochemical analyses. Methods: The present study had a randomized, controlled, double-blinded design. Systemically healthy patients with &ge;20 teeth were enrolled if they had at least two teeth with residual pockets of 6-7 mm depth after at least a month from the completion of active periodontal therapy containing scaling and root planing. Twenty patients were randomly assigned to the test group who used Jellcoat F or the control group who used placebo. Gingival index (GI), plaque index (Pl I), probing pocket depth and bleeding on probing were recorded. In each patient, gingival crevicular fluid (GCF) was collected from one of the teeth with residual pockets, and subgingival plaque from the other. The levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in GCF and Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola in subgingival plaque were determined. After the collections, residual pockets were filled with Jellcoat F or placebo. Patients were instructed to brush their teeth with Jellcoat F or placebo and also apply the gel with a retainer for 10 minutes before sleeping. After 4 weeks, the same examinations were performed. Results: No adverse event was observed. At the baseline, no difference was observed between the test and control groups in age, sex, number of teeth, levels of periodontopathic bacteria, AST and ALT. Comparing the baseline and 4 weeks, only GI and Pl I were significantly decreased in the test group. No other change was found in both test and control groups. Changes of measurements during the 4 weeks were not statistically different between the groups. The effect of Jellcoat F to improve GI remained significant after being adjusted for age and sex. Conclusion: Application of Jellcoat F for 4 weeks on residual pockets after periodontal therapy with teeth brushing and a retainer did not significantly change the levels of periodontopathic bacteria in subgingival plaque, AST and ALT in GCF However, it might suggest the reduction of clinically evaluated supragingival plaque and gingival inflammation.

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

    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   2012.12

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    DOI: 10.1111/j.1744-313X.2012.01124.x

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  • Immunoregulatory gene polymorphisms in Japanese women with preterm births and periodontitis. Reviewed International journal

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

    Journal of reproductive immunology   93 ( 2 )   94 - 101   2012.3

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  • The association of Aggregatibacter actinomycetemcomitans with preeclampsia in a subset of Japanese pregnant women. Reviewed International journal

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

    Journal of clinical periodontology   39 ( 3 )   229 - 38   2012.3

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    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 Reviewed

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

    JOURNAL OF PERIODONTAL RESEARCH   47 ( 1 )   105 - 113   2012.2

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    DOI: 10.1111/j.1600-0765.2011.01411.x

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

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

    Journal of Periodontal Research   46 ( 3 )   292 - 302   2011.6

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    DOI: 10.1111/j.1600-0765.2010.01338.x

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  • The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. Reviewed International journal

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

    Journal of periodontology   81 ( 8 )   1118 - 23   2010.8

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    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. Reviewed International journal

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

    Journal of periodontology   81 ( 6 )   897 - 906   2010.6

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    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. Reviewed International journal

    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   2009.4

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    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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  • FcgammaRIIb polymorphism associates with immune regulation against periodontal bacteria and pregnancy outcomes

    Iwanaga Ruriko, Hirano Emi, Sugita Noriko, Yoshie Hiromasa

    Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology   2009   28 - 28   2009

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    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 Reviewed

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

    JOURNAL OF PERIODONTAL RESEARCH   43 ( 6 )   706 - 711   2008.12

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  • The interleukin-1 and Fcgamma receptor gene polymorphisms in Japanese patients with rheumatoid arthritis and periodontitis. Reviewed International journal

    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   2007.12

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    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 Reviewed

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

    INTERNATIONAL JOURNAL OF IMMUNOGENETICS   34 ( 5 )   369 - 372   2007.10

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

    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   2007.3

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    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. Reviewed International journal

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

    Blood   107 ( 9 )   3600 - 8   2006.5

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    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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  • FcgammaRIIIb genotypes and smoking in periodontal disease progression among community-dwelling older adults in Japan. Reviewed International journal

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

    Journal of periodontology   76 ( 2 )   250 - 5   2005.2

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

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  • Alterations of gene expression in human neutrophils induced by smoking cessation. Reviewed International journal

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

    Journal of clinical periodontology   31 ( 12 )   1110 - 6   2004.12

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    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. Reviewed International journal

    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   2003.3

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

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

    JOURNAL OF PERIODONTAL RESEARCH   36 ( 6 )   390 - 397   2001.12

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

    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   2001.10

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    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.

    DOI: 10.1902/jop.2001.72.10.1324

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  • Analysis of vitamin D and Fcγ receptor polymorphisms in Japanese patients with generalized early-onset periodontitis Reviewed

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

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

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    DOI: 10.1177/00220345010800120501

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

    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

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    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 Reviewed

    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

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Academy of Periodontology  

    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 Reviewed

    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

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    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 Reviewed

    T SUZUKI, N SUGITA, H YOSHIE, K HARA

    JOURNAL OF PERIODONTAL RESEARCH   30 ( 3 )   159 - 166   1995.5

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  • A Rapid Diagnosis for Periodontitis Based on Enzymatic Activity of Periodontopathic Bacteria : Clinical specificity and cut-off value of SK-013

    OHTAKE Tohru, TAKANO Tokiko, KURIHARA Chikako, MINAMIZAKI Nobuki, MIYASHITA Hajime, HASEGAWA Kohji, SUGITA Noriko, SATOH Etsuko, TAI Hideaki, KOBAYASHI Tetsuo, YOSHIE Hiromasa, HARA Kohji, ISODA Ryuutaro, KAWAI Toshihisa, SAHO Teruyuki, OGO Shuuji, MIKI Yasuo, OKADA Hiroshi

    Journal of the Japanese Association of Periodontology   33 ( 1 )   154 - 163   1991.3

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    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    Various laboratory techniques have been applied to the microbiological diagnosis of periodontal disease. However, certain disadvantages persist. In this study we examined the specific peptidase activity in periodontal pockets by using the chair-side test system, SK-013 as a microbiological diagnostics technique. SK-013 can rapidly (within 15 min) evaluate the peptidase activities derived from periodontopathic bacteria such as Treponema denticola and Bacteroides species. We applied SK-013 to patients with periodontitis, gingivitis, dental caries, other types of periodontal infectious disease and periodontally healthy controls and then evaluated the clinical specificity of SK-013, assessing its cut-off level. SK-013 activity was determined both spectrophotometrically and by using the color standard. Phase contrast microscopy was also utilized for determination of subgingival microorganisms. SK-013 activity was specifically detected in the periodontitis group. Setting its cut-off level at 0.2 Try U/ml based on the number of spirochetes in the subgingival pocket, we got good sensitivity, specificity, predictive value and efficacy in terms of the diagnostic value of SK-013. Using the same cut-off level, a good coincidence was also shown in both spectrophotometrically and by using the color standard. These results indicate that SK-013 is a useful chair-side diagnostic method for periodontal disease.

    DOI: 10.2329/perio.33.154

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    Other Link: http://search.jamas.or.jp/link/ui/1993025408

  • Rapid Diagnosis of Periodontitis Based on Enzymatic Activity Derived from Periodontopathic Bacteria : Evaluation of the Efficacy of Periodontal Pocket Curettage by SK-013

    SUGITA Noriko, SATOH Etsuko, TAI Hideaki, KOBAYASHI Tetsuo, YOSHIE Hiromasa, HARA Kohji, OHTAKE Tohru, TAKANO Tokiko, KURIHARA Chikako, MINAMIZAKI Nobuki, MIYASHITA Hajime, HASEGAWA Kohji, ISODA Ryuutaro, KAWAI Toshihisa, SAHO Teruyuki, OGO Shuuji, MIKI Yasuo, OKADA Hiroshi

    Journal of the Japanese Association of Periodontology   33 ( 1 )   164 - 171   1991.3

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    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    The purpose of the present study was to examine the diagnostic value of SK-013 (Sunstar, Osaka) in evaluating the efficacy of periodontal pocket curettage. SK-013 is a highly sensitive reagent which is used to measure the specific peptidase activities produced by Treponema denticola, Bacteroides (Porphyromonas) gingivalis and Bacteroides forsythus. Sixty-four periodontitis patients were selected for the study. Of the 64 patients, 33 were treated by plaque control instruction and periodontal pocket curettage (T group), and the other 31 patients received no treatment for periodontal disease (NT group). One site was monitored in each patient. The clinical status of each site was assessed using clinical indices such as the gingival index (GI), plaque index (PlI), probing depth (PD), attachment level (AL), bleeding on probing (BOP) and tooth mobility. In the T group, the clinical and enzymatic examinations were made at five separate appointments as follows: (1) at baseline prior to plaque control instruction; (2) 4 weeks after plaque control instruction; and (3) 2, 4, and 8 weeks after periodontal pocket curettage. The same examinations were performed but, only at baseline and after 12 weeks, in the NT group. As a result, periodontal pockets were reduced in depth following plaque control instruction, while the enzymatic activity showed no significant change before and after plaque control. Two weeks after periodontal pocket curettage, both clinical indices (GI, PD, AL, BOP) and SK-013 activity were significantly reduced and these improvements were maintained for 4 weeks. No significant discrepancy was observed in the NT group between clinical assessment and enzymatic activity during the experimental period. This finding suggested that SK-013 is a clinically useful diagnostic method for assessing the effect of initial periodontal therapy.

    DOI: 10.2329/perio.33.164

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    Other Link: http://search.jamas.or.jp/link/ui/1993025542

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

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

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

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

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  • A rapid diagnosis for periodontitis based on enzymatic activity of periodontopathic bacteria. Correlation between enzymatic activity, clinical periodontal parameters, and subgingival level of microorganisms.:Correlation between Enzymatic Activity, Clinical Periodontal Parameters, and Subgingival Level of Microorganisms

    OHTAKE Tohru, SAKURAI Chisato, KURIHARA Chikako, MINAMIZAKI Nobuki, KOBAYASHI Makoto, MIYASHITA Hajime, HASEGAWA Kohji, KOBAYASHI Tetsuo, SATOH Etuko, SUGITA Noriko, OKUDA Kazuhiro, YANAGIMURA Mitsuhiro, YOSHIE Hiromasa, HARA Kohji

    JOURNAL OF THE JAPANESE ORGANISATION FOR RESEARCH OF PERIODONTOLOGY   32 ( 1 )   241 - 248   1990

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    Language:Japanese   Publisher:JAPANESE SOCIETY OF PERIODONTOLOGY  

    There have been various laboratory methods for the microbiological diagnosis of periodontal disease. However, there have been some disadvantages in these methods.<BR>In this study of the application of a chair-side test for microbiological diagnosis, the activity of peptidases in periodontal pockets of patients was examined by using the assay system SK-013. SK-013 consists of synthetic substrates and is capable of rapidly (in 15 min) evaluating the activity of specific peptidase from <I>Treponema denticola</I> and <I>Bacteroides species</I>. Using SK-013, we evaluate the correlation betweenthe enzymatic activity, clinical periodontal parameters and subgingival level of microorganisms, including phase contrast microscopy. We calculated the sensitivity and efficacy of SK-013 as a diagnostic indicator in the presence of Spirochetes and in periodontitis. A positive correlation were demonstrated between enzymatic activity, clinical periodontal parameters, the numbers of total cell count, Spirochetes, and M & S ratio. SK-013 was highly sensitive and efficacous (sensitivity: 92%, efficacy: 96%).<BR>We concluded that the assay system SK-013 is a useful chair-side method for diagnosing periodontal disease.

    DOI: 10.2329/perio.32.241

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  • A rapid diagnosis for periodontitis based on the enzymatic activity of periodontopathic bacteria. The application of thESK-013 to the judgment on the effect of initial preparation.:The Application of the SK-013 to the Judgment on the Effect of Initial Preparation

    KOBAYASHI Tetsuo, SATOH Etsuko, SUGITA Noriko, OKUDA Kazuhiro, YANAGIMURA Mitsuhiro, YOSHIE Hiromasa, HARA Kohji, SAKURAI Chisato, KURIHARA Chikako, MINAMIZAKI Nobuki, OHTAKE Tohru, KOBAYASHI Makoto, MIYASHITA Hajime, HASEGAWA Kohji

    JOURNAL OF THE JAPANESE ORGANISATION FOR RESEARCH OF PERIODONTOLOGY   32 ( 1 )   249 - 260   1990

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    Language:Japanese   Publisher:JAPANESE SOCIETY OF PERIODONTOLOGY  

    The purpose of the present study was to examine the diagnostic value of the SK-013 (Sunstar, Osaka) in evaluating the effect of initial preparation. The SK-013 is a highly sensitive reagent to measure peptidase activity specifically produced by <I>Bacteroides gingivalis</I>, <I>Bacteroides forsythus</I>, and <I>Treponema denticola</I>. Thirty-six sites in 16 periodontitis patients were monitored in this study. The clinical status of each site was assessed using the clinical indices such as gingival index (GI), plaque index (PlI), probing depth (PD), and bleeding on probing (BOP). The composition of subgingival microflora in samples was determined using phase contrast microscopy. Clinical, microbiological, and enzymatic examinations were made at five separate appointments, as follows: (1) at baseline prior to plaque control instruction; (2) 4 weeks following plaque control instruction; and (3) 2, 4, 8 weeks following scaling and root planing of periodontal sites. The results of these examinations were compared statistically. The correlation was positive between the total counts of bacteria including spirochetes and motile rods and the enzymatic activity identified using the SK-013. Also the enzymatic profile was highly correlated with microbiological findings other than clinical indices. These results show that the SK-013 is a clinically useful diagnostic method for assessing the effect of initial periodontal therapy.

    DOI: 10.2329/perio.32.249

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Research Projects

  • 歯周炎と死亡率の関連性におけるエネルギー代謝調節遺伝子の役割

    Grant number:24K12911

    2024.4 - 2027.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    杉田 典子

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    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

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  • Analysis of the mechanisms linking periodontitis to rheumatoid arthritis and chronic kidney disease: the potential role of specific autoimmunity

    Grant number:24K12928

    2024.4 - 2027.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • 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

    Grant number:22K10337

    2022.4 - 2025.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization: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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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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  • Analysis of the mechanisms underlying the link between periodontitis and rheumatoid arthritis onset and deterioration: the potential role of glycan modification of autoantibody

    Grant number:21K09891

    2021.4 - 2025.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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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

    Grant number:21K09871

    2021.4 - 2024.3

    System name:科学研究費助成事業

    Research category:基盤研究(C)

    Awarding organization:日本学術振興会

    杉田 典子

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

    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

    Grant number:18H03013

    2018.4 - 2021.3

    System name:科学研究費助成事業 基盤研究(B)

    Research category:基盤研究(B)

    Awarding organization: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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    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

    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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  • Uncoupling protein gene polymorphisms associated with severe periodontitis in Japanese adults

    Grant number:18K09572

    2018.4 - 2021.3

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Sugita Noriko

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    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Uncoupling proteins (UCP) are mitochondrial membrane transporters which regulate energy expenditure and the metabolism of lipids and carbohydrates. UCP2 is expressed in a broad range of cells including immune cells. UCP3 is expressed in skeletal muscle cells and spleen. We have previously reported associations between the UCP gene polymorphisms and severe periodontitis in postmenopausal women. In vitro study revealed that UCP2 attenuated production of reactive oxygen species and proinflammatory cytokines. In this study, we validated the associations in another Japanese adult population.All outpatients of Sado General Hospital were invited to participate in a cohort study. The final subjects were composed of 115 men and 100 women (mean age 67 years). Edentulous person and participants with missing data were excluded. Adjusted for age, sex, diabetes, body mass index and smoking, the UCP2 rs659366 and the UCP3 rs2075577 were significantly associated with severe periodontitis.

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  • Uncoupling protein genes associated with periodontitis, diabetes, obesity and osteoporosis in postmenopausal women

    Grant number:15K11384

    2015.4 - 2018.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    Sugita Noriko, NAKAMURA KAZUTOSHI

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    Grant amount:\4810000 ( Direct Cost: \3700000 、 Indirect Cost:\1110000 )

    Uncoupling proteins (UCPs) are mitochondrial membrane transporters which regulate the metabolism of carbohydrate, lipid, and bone. Genetic polymorphisms in UCPs are risk factors for diabetes, obesity and osteoporosis. Periodontitis has been reported to be associated with the systemic diseases. Therefore, we investigated the associations among UCP polymorphisms, periodontitis, diabetes, obesity and osteoporosis. As a result, UCP2 and UCP3 polymorphisms were associated with severe periodontitis independently of the systemic diseases, though the prevalence of periodontitis was not associated with the polymorphisms. Moreover, to elucidate the biological role of UCP2 in periodontitis, we performed experiments in human macrophages. The suppression of UCP2 expression significantly elevated the levels of reactive oxygen species and proinflammatory cytokines. The results suggested that UCPs may play roles in the pathogenesis of periodontitis.

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  • Associations between PPARgamma gene polymorphism and periodontitis, obesity and osteoporosis in postmenopausal women

    Grant number:24593121

    2012.4 - 2015.3

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SUGITA Noriko, NAKAMURA Kazutoshi

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    Grant amount:\5330000 ( Direct Cost: \4100000 、 Indirect Cost:\1230000 )

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear hormone receptor and regulates inflammation, lipid and bone metabolism. Previous studies reported associations between polymorphisms in PPARgamma gene and inflammation, obesity and osteoporosis. Postmenopausal women have higher risks for these diseases. Therefore, to elucidate whether PPARgamma Pro12Ala polymorphism was a common risk factor for the diseases, we assessed possible associations between the genotypes and parameters of obesity, osteoporosis and periodontitis in 359 postmenopausal Japanese women living in Niigata City. As a result, the Ala allele carriage was suggested to enhance associations between periodontitis and obesity or osteoporosis. The finding might contribute to risk diagnosis and suggest possible effects of PPARgamma regulation in therapies of these diseases.

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  • Peroxisome proliferator-activated receptor gamma polymorphism andperiodontitis, preterm birth and obesity in pregnant Japanese women

    Grant number:21659480

    2009 - 2011

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category:Grant-in-Aid for Challenging Exploratory Research

    Awarding organization:Japan Society for the Promotion of Science

    YOSHIE Hiromasa, SUGITA Noriko, KIKUCHI Akira

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    Grant amount:\3180000 ( Direct Cost: \3000000 、 Indirect Cost:\180000 )

    PPAR gamma is a nuclear hormone receptor which regulates lipid metabolism and production of inflammatory cytokines. A functional genetic polymorphism Pro12Ala has been reported. Recent studies have suggested an association between periodontitis and preterm birth or obesity. We investigated relationships between PPAR gamma polymorphism, periodontitis, preterm birth and obesity in pregnant Japanese women. There was no significant association between periodontitis and preterm birth, or between periodontitis and obesity. However, a significant association of the polymorphism and periodontitis was found in the Japanese pregnant women.

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  • Polymorphisms for immunoregulatory genes in women with preterm birth and periodontitis

    Grant number:19592385

    2007 - 2008

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SUGITA Noriko

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    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

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  • Immune regulation by the inhibitory IgG receptor related to the susceptibility of periodontitis

    Grant number:17592159

    2005 - 2006

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    SUGITA Noriko, KOBAYASHI Tetsuo

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    Human low affinity Fc receptor IIb (FcγRIIb) is one of IgG receptors and suppress the activation of B lymphocytes through cross-linking with B cell receptor (BCR) via immune-complexes. This function of FcγRIIb is essential for the negative regulation of antibody productions. Our previous study has demonstrated the gene polymorphism FcγRIIB-I232T to be significantly associated with periodontitis. In this study, we examined the possibility that IgG antibody responses to periodontopathic bacteria Porphyromonas gingivalis (P.gingivalis) are different between periodontitis patients with different genotypes. Forty-seven patients with periodontitis were genotyped for FcγRIIB-I232T with the direct sequencing of genome DNA. Serum levels of nonspecific total IgG and specific IgG subclasses for the sonicate of P.gingivalis, the recombinant 40-kDa outer membrane protein (OMP) and 200kDa antigenic protein (AP) were determined. FcγRIIB-232T carrier revealed significantly lower IgG2 response to P.gingivalis 40-kDa OMP compared to noncarrier (P<0.05). Lower responses of FcγRIIB-232T carrier were also observed in specific IgG and IgG1 levels which were not statistically significant. No significant difference of antibody response to P.gingivalis sonicate or 200-kDa AP was observed between FcγRIIB-232T carrier and noncarrier. In FcγRIIB-232T noncarrier, there was a subgroup of patients showing high levels of IgG2 response in concert with the high average of probing depth. In contrast, all FcγRIIB-232T carriers revealed lower levels of IgG2 response. These results suggest that the association of FcγRIIB-232T allele with periodontitis might be attributed to the lower level of antibody response to P.gingivalis.
    We investigated the expression of FcγRIIb in peripheral blood leukocytes and gingiva from periodontitis patients. Expression levels of FcγRIIb on B lymphocytes were lower in patients with periodontitis compared to controls. This might be a cause of less effective inhibition of overactivation of B lymphocytes in the pathogenesis of periodontitis. Expression of FcγRIIb was also confirmed in human gingiva with periodontitis.

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  • Determination of common risk genes associated with periodontitis and autoimmune disease

    Grant number:15390644

    2003 - 2005

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    KOBAYASHI Tetsuo, SUGITA Noriko, YAMAMOTO Kouji

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    Grant amount:\14500000 ( Direct Cost: \14500000 )

    To identify common risk genes associated with periodontitis and autoimmune disease, we have evaluated the distributions of the genotypes of the immunoglobulin Fc receptors (FcR) and inflammatory cytokines such as interleukin-1 (IL-1) in patients with both diseases. Our results were as follows :
    1.A significant association was found between FcγRIIA gene and periodontitis and autoimmune disease, as demonstrated by a case-control study with 213 chronic periodontitis patients, 87 patients with systemic lupus erythematosus (SLE), and 209 controls. These results were supported by a functional study showing a difference in IL-1 production between the FcγRIIA genotypes.
    2.FcγRIIB nt 775T/C was shown to be a candidate common risk polymorphism associated with both diseases by a case-control study with 58 chronic periodontitis patients, 66 SLE patients, and 44 controls. This FcγRIIB genotype has been suggested to regulate antibody response specific for Porphyromonas gingivalis 40 kDa outer membrane protein.
    3.IL-1B +3954 was shown as a gene related to onset of rheumatoid arthritis (RA) by an association study with 140 chronic periodontitis patients, 50 aggressive periodontitis patients, 46 RA patients, and 149 controls.

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  • Bone homeostasis-related genes associated with susceptibility to periodicities

    Grant number:13470461

    2001 - 2003

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    YOSHIE Hiromasa, YAMAZAKI Kazuhisa

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    Grant amount:\16500000 ( Direct Cost: \16500000 )

    Vitamin D receptor (VDR), Tumor necrosis factor alpha (TNF-α), TNF receptor, Interleukin-1 (IL-1), IL-1 receptor antagonist (IL-1RA), and CD14 had been reported to be related with bone homeostasis and were selected as candidate genes in this study. Association between polymorphisms in the candidate genes and susceptibility to aggressive or chronic periodontitis were assessed in case-control studies. Genotypes were determined using genomic DNA obtained from Japanese patients and healthy controls.
    In Japanese subjects, the polymorphism in the 5'-flanking region of TNF-α gene was not associated with susceptibility to generalized aggressive periodontitis (G-AgP), whereas the combination of genotypes of VDR and IgG receptor, FcγRIIIb, and VNTR (variable number of tandem repeats) in IL-1RA gene showed significant associations with the susceptibility to G-AgP. Single nucleotide polymorphisms (SNPs) in TNFR1 and FcγRIIb genes were associated with G-AgP, respectively. A polymorphism in CD14 gene was not related to the development of periodontitis, but suggested to be related to early disease activity.
    These analyses demonstrated that a number of genes related to bone homeostasis were relevant with the development of periodontitis as combinatorial factors. The findings in this study may be useful for a diagnosis system with multiple genetic factors of periodontitis.

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  • Genetic diagnosis and immunoglobulin A receptor targeting therapy for periodontitis

    Grant number:13557189

    2001 - 2003

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    KOBAYASHI Tetsuo, SUGITA Noriko

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    Grant amount:\11700000 ( Direct Cost: \11700000 )

    -1.Genetic diagnosis of periodontisis risk :
    Sequence analyses of immunoglobulin A and G Fc receptor (neutrophil-specific FcαRI, CD89 and B cell-specific FcγRIIB, CD32) indicated one and seven single-nucleotide substitutions, respectively. Of these polymorphisms, FcαRI nt 324A/G and FcγRIIB nt 775T/C have been shown to be associated with aggressive periodontitis risk. Neutrophils (PMN) from peripheral blood and gingival crevicular fluid (GCF) of periodontitis patients exhibited a decreased phagocytosis in the nt 324 A/A as compared to the nt 324 G/G patients. These results suggest FcαRI nt 324A/A patients to be high-susceptibility to aggressive periodontitis.
    -2.Immunoglobulin A receptor targeting therapy :
    The bispecific antibody (BsAb) was constructed from anti-Porphyromonas gingivalis and anti-FcαRI monoclonal antibody (MAb). Flow cytometric analyses showed opsonic activity for GCF PMN to be comparable between BsAb and control anti-P. gingivalis MAb. However, a BsAb significantly promoted phagocytosis and killing activity of GCF PMN, which exhibiting higher FcαRI expression levels than PB PMN. These data suggest BsAb targeting toward GCF PMN FcαRI to be effective for improvement of antibacterial immunity in periodontitis patients.

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  • Fc receptor gene analysis and immunotherapy with bispecific antibody for periodontal disease

    Grant number:12557191

    2000 - 2002

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    YOSHIE Hiromasa, SUGITA Noriko, KOBAYASHI Tetsuo

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    Grant amount:\10300000 ( Direct Cost: \10300000 )

    - Diagnosis of periodontisis risk with Fc receptor gene polymorphisms :
    The association of FcR polymorphisms with severity of chronic periodontitis (CP) was examined by means of allele-specific polymerase chain reactions. A significant over-representation of FcRIIIa-158V allele in severe CP patients as compared to moderate AP patients (P = 0.03). In addition, we found a strong association between CP severity and FcR composite genotype comprising FcRIIIA-158V plus FcRIIIB-NA2 (odds ratio 4.7, P = 0.002). The association study consisted of 60 SLE patients, age-matched 42 healthy subjects with periodontitis, and 42 healthy subjects without periodontitis indicated FcγRIIa-R131 allele to be a common risk factor for SLE and periodontitis. Variation screening of neutrophil-specific FcRIIIB and B cell-specific FcRIIB genes showed new one and seven single nucleotide polymorphisms, respectively, and documented the association of FcRIIB nt 775T/C with aggressive periodontitis risk. These results suggest FcR genotype to be associated with susceptibility to periodontitis.
    - Immunotherapy of periodontitis with human monoclonal antibody :
    Human immunoglobulin (Ig)-producing mice were immunized by intraperitoneal injection of recombinant 40-kDa outer membrane protein (r40-kDa OMP) of Porphyromonas gingivalis. Total 99 clones of human monoclonal antibodies (hMAb) specific for r40-kDa OMP were obtained, all of which was IgG isotype (IgG1 : 84 clones ; IgG2 : 11 clones ; IgG4 : 4 clones). The binding activity of hMAb to r40-kDa OMP was shown to be almost same as that of human polyclonal antibody (60 times higher in concentration). The opsonophagocytic activity of hMAb clones were also indicated to be almost same as that of human polyclonal antibody (10000 times higher in concentration). This hMAb was shown to enhance neutrophil phagocytosis of P. gingivalis.

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  • Inhibitory IgG receptor as an immunoregulator and a relevant factor for periodontitis susceptibility

    Grant number:12672033

    2000 - 2002

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KOBAYASHI Tetsuo, SUGITA Noriko

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    Grant amount:\3300000 ( Direct Cost: \3300000 )

    FcγRIIB as an immunoregulator :
    The inhibitory IgG receptor, FcγRIIB was genetically examined to clarify its role as an immunoregulator. FcγRIIB nucleotide sequence was screened on genomic DNA isolated from peripheral blood of 100 healthy donors with informed consent by means of direct sequencing. We identified 5 and 2 single nucleotide substitutions in exon 4 and intron 4, respectively. Of these, 3 substitutions indicated amino acid changes, which might correspond to the potential splicing sites. However, no change of splicing in the FcγRIIB transcripts was identified with the determination of cDNA sequence. These substitutions located in the extracellular IgG binding domain might induce the structural change of FcγRIIB.
    FcγRIIB as a relevant factor for periodontitis susceptibility
    We have determined FcγRIIB genotypes for the exon 4 and intron 4, as well as exon 5 bi-allelic polymorphisms in 33 aggressive periodontitis (AGP) patients, 73 chronic periodontitis (CP) patients, and 71 healthy controls, with informed consent, by means of direct sequencing or polymerase chain reaction. Our results indicated a significant over-representation of the nt 775 C allele in the AGP group compared with the control group (AGP vs. Control : 17% vs. 6% ; P=0.01, Odds ratio 3.4), suggesting FcγRIIB gene to be a candidate factor associated with susceptibility to periodontitis.

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  • Development of Immunotherapy of Refractory Periodontitis with Anti-Fc Receptor Bispecific Antibodies

    Grant number:12672032

    2000 - 2001

    System name:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category:Grant-in-Aid for Scientific Research (C)

    Awarding organization:Japan Society for the Promotion of Science

    KOBAYASHI Tetsuo, SUGITA Noriko

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    Grant amount:\3100000 ( Direct Cost: \3100000 )

    After informed consent was obtained, gingival crevicular fluid (GCF)- and peripheral blood (PB)-neutrophils (PMN) from 21 adult periodohtitis patients were analyzed for their IgG and IgA PcR (FcγR and FcαR) expression and function by studying IgG- and IgA-mediated elimination of Porphyromonas gingivalis. GCF-PMN exhibited increased FcαR levels and decreased FcγR levels compared to PB-PMN. Functional studies revealed GCF-PMN to exhibit a decreased capacity to phagocytose and kill IgG1-opsonized P.gingivalis compared to PB-PMN. IgA1-mediated phagocytosis and killing capacity was, however, comparable between GCF- and PB-PMN. These results suggest FcαR to represent a candidate target for FcR-directed immunotherapy of periodontitis.
    Recombinant 40-kDa outer membrane protein (rOMP-40) of P. gingivalis was obtained by purification with homogeneity from the cell sonicate. Human immunoglobulin producing mice, KM mouse^<TM>, were immunized by injection of rOMP-40. The spleen cells were collected, and then fused with the mouse myeloma cell line. Total 102 clones of human mononlonal antibodies (hMAbs) specific for rOMP-40 were obtained and screened by enzyme-linked immunosorbent assay. The number of IgG was 99, whereas three were IgM. IgA clone was not established. The opsonophagocytic activity of hMAb clones showing high reactivity with rOMP-40 was measured. Our results indicated hMAb clones to be significantly higher in opsonophagocytic activity than human polyclonal antibodies. These results provided the possibility that topical application of hMAbs would be aid in PMN-dependent elimination of P. gingivalis.

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  • Immunoglobulin receptors as genetic risk factors of periodontitis

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    Grant type:Competitive

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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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    Grant type:Competitive

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Teaching Experience

  • 生涯にわたる歯と咬合

    2022
    Institution name:新潟大学

  • 一般口腔保健管理学II

    2021
    Institution name:新潟大学

  • 臨床実習Ⅰ

    2020
    Institution name:新潟大学

  • 歯周病学

    2020
    Institution name:新潟大学

  • 総合模型実習

    2020
    -
    2023
    Institution name:新潟大学

  • 臨床実習Ⅲ

    2020
    Institution name:新潟大学

  • 歯科衛生学実習Ⅱ

    2019
    Institution name:新潟大学

  • 臨床実習Ⅱ

    2019
    Institution name:新潟大学

  • 早期臨床実習ⅠB

    2019
    -
    2021
    Institution name:新潟大学

  • 早期臨床実習Ⅱ

    2018
    -
    2021
    Institution name:新潟大学

  • 早期臨床実習Ⅰ

    2016
    -
    2021
    Institution name:新潟大学

  • 選択実習Ⅱ

    2015
    -
    2019
    Institution name:新潟大学

  • 臨床予備実習

    2012
    Institution name:新潟大学

  • 歯周病学実習

    2010
    -
    2020
    Institution name:新潟大学

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