Updated on 2023/11/29

写真a

 
TAKASHIBA Shogo
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
Contact information
メールアドレス
Profile
歯や口の健康だけではなく全身の健康にいろいろと関係する「歯周病」の研究を,細菌学,免疫学,分子細胞生物学の観点によって,基礎から臨床まで幅広く行っています。 特に,感染の制御,炎症の制御,そして組織再生の制御の3分野での視点でもって,研究を発展させています。 最近では,臨床現場の先生方と連携した臨床疫学・観察・介入の研究へと発展させ,さらには種々の製品開発に関わる研究へと視野を拡大しています。
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Degree

  • Ph.D. ( 1990.3   Okayama University )

  • D.D.S. ( 1986.3   Okayama University )

Research Interests

  • Periodontology

  • Endodontology

  • Periodontal Science (Periodontology & Endodontology)

  • Dentistry

Research Areas

  • Life Science / Conservative dentistry

  • Life Science / Conservative dentistry

Education

  • Okayama University   大学院 歯学研究科  

    1986.4 - 1990.3

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    Country: Japan

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  • Okayama University   歯学部   歯学科

    1980.4 - 1986.3

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    Country: Japan

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Research History

  • Okayama University   学術研究院 医歯薬学域   Professor   DDS, PhD

    2021.4

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    Country:Japan

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  • Okayama University   Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Periodontal Science   Professor   DDS, PhD

    2005.4 - 2021.3

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    Country:Japan

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  • Okayama University   Graduate School of Medicine and Dentistry, Periodontal Science   Professor   DDS, PhD

    2002.4 - 2005.3

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    Country:Japan

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  • Okayama University   Graduate School of Medicine and Dentistry, Periodontal Science   Associate Professor   DDS, PhD

    2001.4 - 2002.3

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    Country:Japan

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  • 文部科学省在外研究員(University of Southern California & National Institute of Dental and Craniofacial Research, USA)

    1996.2 - 1996.4

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    Country:United States

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  • Okayama University   Dental School   Associate Professor   DDS, PhD

    1995.11 - 2001.3

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    Country:Japan

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  • Okayama University   Dental School   Assistant Professor   DDS, PhD

    1994.12 - 1995.11

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    Country:Japan

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  • Eastman Dental Center (Rochester, NY, USA)   Periodontology (Prof. Van Dyke Lab)   Visiting Scientist   DDS, PhD

    1992.4 - 1994.11

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    Country:United States

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  • Okayama University   University Hospital of Dentistry   Assistant Professor   DDS, PhD

    1990.4 - 1992.3

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    Country:Japan

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Professional Memberships

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Committee Memberships

  • International Association for Dental Research   President of Periodontal Research Group  

    2021.7   

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  • 日本未病学会   理事  

    2020   

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    Committee type:Academic society

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  • 日本歯科保存学会   理事  

    2002.4   

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    Committee type:Academic society

    日本歯科保存学会

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  • 日本歯周病学会   理事  

    2002.4   

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    Committee type:Academic society

    日本歯周病学会

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  • 岡山歯学会   理事  

    2002.4   

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    Committee type:Academic society

    岡山歯学会

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  • 日本口腔検査学会   理事,学術委員会委員長  

    2021.4   

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    日本口腔検査学会

  • 日本歯周病学会   常任理事,研究委員会委員長  

    2021.4 - 2023.3   

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    Committee type:Academic society

  • International Association for Dental Research   President Elect of Periodontal Research Group  

    2020.3 - 2021.7   

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  • International Association for Dental Research   President Elect of Periodontal Research  

    2020.3 - 2021.7   

  • 日本未病学会   理事  

    2020   

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    Committee type:Academic society

    日本未病システム学会から日本未病学会へ改称(2020〜)

  • 日本歯周病学会   常任理事,学会あり方委員会委員長  

    2019.4 - 2021.3   

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  • 日本歯周病学会   常任理事,学会あり方委員会委員長  

    2019.4 - 2021.3   

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    Committee type:Academic society

  • International Association for Dental Research   Vice President of Periodontal Research Group  

    2019.3 - 2020.3   

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  • International Association for Dental Research   Vice President of Periodontal Research  

    2019.3 - 2020.3   

  • International Association for Dental Research   Editorial Board Member  

    2019.1 - 2021.12   

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    国際歯科研究学会

  • International Association for Dental Research   Editorial Board Member  

    2019.1 - 2021.12   

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  • 日本未病システム学会   理事  

    2019   

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  • 日本未病システム学会   理事  

    2019   

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    Committee type:Academic society

    日本未病システム学会

  • 日本予防医学会   理事  

    2017.9   

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    Committee type:Academic society

    日本予防医学会

  • 日本歯科保存学会   常任理事,医療合理化委員会委員長  

    2017.4 - 2021.3   

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    Committee type:Academic society

    日本歯科保存学会

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  • 日本歯周病学会   常任理事,専門医委員会医員長  

    2017.4 - 2019.3   

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    Committee type:Academic society

    日本歯周病学会

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  • International Academy of Periodontology   Board Menber  

    2017.1   

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  • 日本予防医学会   理事  

    2017   

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  • 日本歯周病学会   常任理事,研究委員会医員長  

    2011.4 - 2015.3   

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    Committee type:Academic society

    日本歯周病学会

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  • 日本口腔検査学会   理事  

    2011   

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    日本口腔検査学会

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  • 日本歯周病学会   常任理事,用語委員会委員長  

    2009.4 - 2011.3   

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    Committee type:Academic society

    日本歯周病学会

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  • 日本歯周病学会   2009年(第52回)春季日本歯周病学会 学術大会大会長  

    2009   

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    Committee type:Academic society

    日本歯周病学会

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  • 日本歯科保存学会   常任理事,編集委員会委員長  

    2007.4 - 2010.3   

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    Committee type:Academic society

    日本歯科保存学会

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  • 日本未病システム学会   評議員  

    2006 - 2018   

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    Committee type:Academic society

    日本未病システム学会

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  • International Association for Dental Research   Editorial Board Member  

    2001.1 - 2004.12   

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  • International Association for Dental Research   Abstract Reviewer (Periodontal Research Group)  

    2000.1 - 2004.12   

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Papers

  • Functionalized Graphene Oxide Shields Tooth Dentin from Decalcification. Reviewed International journal

    MZI Nizami, Y Nishina, T Yamamoto, Y Shinoda-Ito, S Takashiba

    Journal of dental research   99 ( 2 )   182 - 188   2020.2

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    This in vitro study assessed the efficacy of functionalized graphene oxide (f-GO) nanocomposites on the decalcification of dentin, because dental caries of the root surface is becoming one of the new problems in aged society. Hydroxyapatite plates (HAP) and dentin slices were coated with f-GO nanocomposites by comparing them to silver diamine fluoride as a positive control, then treated with decalcification solutions such as ethylenediaminetetraacetic acid and citrate at 37°C for 24 h. Scanning electron microscopy (SEM) revealed significant protection of the surface morphology of HAP and dentin. On the other hand, a cariogenic Streptococcus mutans growth was inhibited by f-GO nanocomposites. In addition, cytotoxicity of them to epithelial cells was much less than that of povidone-iodine, which is commonly used for oral disinfectant. We synthesized 5 different f-GO nanocomposites such as GO-silver (Ag), GO-Ag-calcium fluoride (CaF2), GO-CaF2, GO-zinc, and GO-tricalcium phosphate (Ca3(PO4)2). They were standardized by evaluating under SEM, transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetry analysis (TGA), and Raman spectra after being synthesized in an aseptic technique. The abilities of GO-Ag, GO-Ag-CaF2, and GO-CaF2 nanocomposites were most preventive for decalcification. In addition, GO-Ag and GO-Ag-CaF2 almost completely inhibited S. mutans growth. However, they did not exhibit cytotoxicity to epithelial cells except at the highest concentration (0.1 w/v%) of GO-Ag and GO-Ag-CaF2. Furthermore, these f-GO nanocomposites exhibited less or no discoloration of dentin, although commonly used silver diamine fluoride causes discoloration of dentin to black. Thus, these f-GO nanocomposites are useful to protect dental caries on the tooth root that becomes a social problem in aged society.

    DOI: 10.1177/0022034519894583

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  • 多施設後ろ向き観察研究による臨床指標としての歯周炎症表面積の基準値 Reviewed

    井上 裕貴, 畑中 加珠, 山本 直史, 平田 貴久, 三辺 正人, 山本 龍生, 内藤 徹, 山本 松男, 佐藤 秀一, 石幡 浩志, 稲垣 幸司, 三谷 章雄, 中島 啓介, 漆原 譲治, 高柴 正悟

    日本歯周病学会会誌   61 ( 4 )   159 - 167   2019.12

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    Authorship:Last author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:(NPO)日本歯周病学会  

    歯周炎症表面積(periodontal inflamed surface area:PISA)は,歯周組織の炎症部の面積を表す新たな歯周病の臨床指標である。従来伝わりづらかった歯周病の炎症程度を歯科以外の医療従事者が理解する上で,有用な指標であると考えられる。しかし,歯周病の程度や治療によるPISAの基準は未だ不明である。そこで,本研究は,日本歯周病学会が設ける歯周病専門医・認定医の電子申請書類のデータから各治療フェーズにおけるPISAの値を調べ,歯周病治療に伴う炎症度の基準値を提案することを目的とした。8施設で取得した113症例を用いて,Nesseらの方法によって歯周ポケット深さとプロービング時の出血からPISAを算出した。その結果,PISAの中央値は,初診時1,271.4mm2,歯周基本治療終了時211.8mm2,SPT移行時52.1mm2,そして最新SPT時30.0mm2であった。また,PISAはBOPと高い相関を示し(p<0.001),BOPよりも鋭敏に治療効果を反映した。以上から,中等度以上の歯周炎においてPISAを用いると,初診時は表面積約1,500mm2の歯周組織の炎症がSPT時は100mm2未満(初診時の約7%)に減少することが明らかになった。今後,更なるデータの蓄積および詳細な分析を行いながらPISAの使用を普及させると,PISAは医科歯科連携の際に歯周病炎症を伝える指標になり得ると考える。(著者抄録)

    DOI: 10.2329/perio.61.159

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  • Acceleration of bone regeneration of horizontal bone defect in rats using collagen-binding basic fibroblast growth factor combined with collagen scaffolds. Reviewed International journal

    Shin Nakamura, Takashi Ito, Kentaro Okamoto, Takehiko Mima, Kentaro Uchida, Yasir D Siddiqui, Masahiro Ito, Masako Tai, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Tadashi Yamamoto, Osamu Matsushita, Shogo Takashiba

    Journal of periodontology   90 ( 9 )   1043 - 1052   2019.9

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    BACKGROUND: Basic fibroblast growth factor (bFGF) has been applied for periodontal regeneration. However, the application depends on bone defect morphology because bFGF diffuses rapidly from defect sites. In a previous study, collagen-binding bFGF (CB-bFGF) has been shown to enhance bone formation by collagen-anchoring in the orthopedic field. The aim of this study is to demonstrate the efficacy of CB-bFGF with collagen scaffolds in bone regeneration of horizontal bone defect. METHODS: Cell proliferation activity and collagen binding activity of CB-bFGF was confirmed by WST-8 assay and collagen binding assay, respectively. The retention of CB-bFGF in the collagen sheet (CS) was measured by fluorescence imaging. The rat horizontal alveolar bone defect model was employed to investigate the efficacy of CB-bFGF with collagen powder (CP). After 4 and 8 weeks, the regenerative efficacy was evaluated by microcomputed tomography, histological, and immunohistochemical analyses. RESULTS: CB-bFGF had a comparable proliferation activity to bFGF and a collagen binding activity. CB-bFGF was retained in CS longer than bFGF. At 8 weeks postoperation, bone volume, bone mineral content, and new bone area in CB-bFGF/CP group were significantly increased compared with those in other groups. Furthermore, epithelial downgrowth was significantly suppressed in CB-bFGF/CP group. At 4 weeks, the numbers of osteocalcin, proliferating cell nuclear antigen, and osteopontin-positive cells at the regeneration site in CB-bFGF/CP group were greater than those in other groups. CONCLUSIONS: CB-bFGF/CP effectively promoted bone regeneration of horizontal bone defect possibly by sustained release of bFGF. The potential of CB-bFGF composite material for improved periodontal regeneration in vertical axis was shown.

    DOI: 10.1002/JPER.18-0674

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  • Resolvin D2 Induces Resolution of Periapical Inflammation and Promotes Healing of Periapical Lesions in Rat Periapical Periodontitis Reviewed International coauthorship International journal

    Yasir Dilshad Siddiqui, Kazuhiro Omori, Takashi Ito, Keisuke Yamashiro, Shin Nakamura, Kentaro Okamoto, Mitsuaki Ono, Tadashi Yamamoto, Thomas E. Van Dyke, Shogo Takashiba

    Frontiers in Immunology   10   2019.2

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    Authorship:Last author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Frontiers Media SA  

    DOI: 10.3389/fimmu.2019.00307

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  • Quantitative real-time PCR using TaqMan and SYBR Green forActinobacillus actinomycetemcomitans,Porphyromonas gingivalis,Prevotella intermedia,tetQgene and total bacteria Reviewed

    Hiroshi Maeda, Chiyo Fujimoto, Yasuhiro Haruki, Takemasa Maeda, Susumu Kokeguchi, Millan Petelin, Hideo Arai, Ichiro Tanimoto, Fusanori Nishimura, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   39 ( 1 )   81 - 86   2003.10

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    Authorship:Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    DOI: 10.1016/s0928-8244(03)00224-4

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  • Induced TNF-alpha and IL1-beta Production by Human Monocytes Reviewed International coauthorship International journal

    L Shapira, S Takashiba, C Champagne, S Amar, TE Van Dyke

    JOURNAL OF IMMUNOLOGY   153 ( 4 )   1818 - 1824   1994.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:AMER ASSOC IMMUNOLOGISTS  

    Bacterial LPS stimulates human monocytes to secrete inflammatory cytokines, which are involved in several disease processes. However, the mechanism of LPS activation of cytokine expression and secretion is not completely understood. In this study, we investigated the signal transduction pathways involved in LPS-stimulated TNF-alpha and IL-1 beta secretion. TNF-alpha and IL-1 beta secretion were completely blocked by protein kinase C (PKC) and cyclic nucleotide-dependent protein kinase inhibitor, H-7, but were not affected by H-89, a specific cyclic nucleotide-dependent protein kinase inhibitor. In addition, LPS was found to induce activation of PKC, reaching maximal activity at 30 min and returning to unstimulated levels after 60 min. LPS stimulation only slightly increased intracellular levels of diacylglycerol, the natural activator of PKC, and pretreatment of monocytes with the diacylglycerol-kinase inhibitor, R59022, did not affect LPS-stimulated TNF-alpha secretion. LPS-induced PKC activation was found not to be affected by blocking of the LPS receptor, CD14, with mAb or by inhibition of protein tyrosine kinase with herbimycin A. However, these agents suppressed LPS-induced TNF-alpha secretion and TNF-alpha mRNA accumulation. The results suggest that TNF-alpha and IL-1 beta secretion after LPS stimulation of human monocytes requires the activation of protein tyrosine kinase and PKC, upstream to the activation of gene transcription. The activation of PKC by LPS is probably mediated by a diacylglycerol-independent pathway.

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  • Ligneous periodontitis exacerbated by Behçet's disease in a patient with plasminogen deficiency and a stop-gained variant PLG c.1468C > T: a case report. International journal

    Yuki Shinoda-Ito, Anna Hirai, Kazuhiro Omori, Hidetaka Ideguchi, Hideki Yamamoto, Fumino Kato, Kyoichi Obata, Tatsuo Ogawa, Keisuke Nakano, Takato Nakadoi, Eri Katsuyama, Soichiro Ibaragi, Tadashi Yamamoto, Hitoshi Nagatsuka, Akira Hirasawa, Shogo Takashiba

    BMC oral health   23 ( 1 )   843 - 843   2023.11

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    Language:English   Publishing type:Research paper (scientific journal)  

    BACKGROUND: Plasminogen serves as the precursor to plasmin, an essential element in the fibrinolytic process, and is synthesized primarily in the liver. Plasminogen activation occurs through the action of plasminogen activator, converting it into plasmin. This conversion greatly enhances the fibrinolytic system within tissues and blood vessels, facilitating the dissolution of fibrin clots. Consequently, congenital deficiency of plasminogen results in impaired fibrin degradation. Patients with plasminogen deficiency typically exhibit fibrin deposits in various mucosal sites throughout the body, including the oral cavity, eyes, vagina, and digestive organs. Behcet's disease is a chronic recurrent systemic inflammatory disease with four main symptoms: aphthous ulcers of the oral mucosa, vulvar ulcers, skin symptoms, and eye symptoms, and has been reported worldwide. This disease is highly prevalent around the Silk Road from the Mediterranean to East Asia. We report a case of periodontitis in a patient with these two rare diseases that worsened quickly, leading to alveolar bone destruction. Genetic testing revealed a novel variant characterized by a stop-gain mutation, which may be a previously unidentified etiologic gene associated with decreased plasminogen activity. CASE PRESENTATION: This case report depicts a patient diagnosed with ligneous gingivitis during childhood, originating from plasminogen deficiency and progressing to periodontitis. Genetic testing revealed a suspected association with the PLG c.1468C > T (p.Arg490*) stop-gain mutation. The patient's periodontal condition remained stable with brief intervals of supportive periodontal therapy. However, the emergence of Behçet's disease induced acute systemic inflammation, necessitating hospitalization and treatment with steroids. During hospitalization, the dental approach focused on maintaining oral hygiene and alleviating contact-related pain. The patient's overall health improved with inpatient care and the periodontal tissues deteriorated. CONCLUSIONS: Collaborative efforts between medical and dental professionals are paramount in comprehensively evaluating and treating patients with intricate complications from rare diseases. Furthermore, the PLG c.1468C > T (p.Arg490*) stop-gain mutation could contribute to the association between plasminogen deficiency and related conditions.

    DOI: 10.1186/s12903-023-03586-8

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  • Novel Iron Chelators, Super-Polyphenols, Show Antimicrobial Effects against Cariogenic Streptococcus mutans. International journal

    Yuki Shinoda-Ito, Kazuhiro Omori, Takashi Ito, Masaaki Nakayama, Atsushi Ikeda, Masahiro Ito, Toshiaki Ohara, Shogo Takashiba

    Antibiotics (Basel, Switzerland)   12 ( 11 )   2023.10

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    Language:English   Publishing type:Research paper (scientific journal)  

    Dental caries are an oral infectious disease that can affect human health both orally and systemically. It remains an urgent issue to establish a novel antibacterial method to prevent oral infection for a healthy life expectancy. The aim of this study was to evaluate the inhibitory effects of novel iron chelators, super-polyphenols (SPs), on the cariogenic bacterium Streptococcus mutans, in vitro. SPs were developed to reduce the side effects of iron chelation therapy and were either water-soluble or insoluble depending on their isoforms. We found that SP6 and SP10 inhibited bacterial growth equivalent to povidone-iodine, and viability tests indicated that their effects were bacteriostatic. These results suggest that SP6 and SP10 have the potential to control oral bacterial infections such as Streptococcus mutans.

    DOI: 10.3390/antibiotics12111562

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  • プロトンポンプ阻害剤服用時に歯周病原細菌が腸内細菌叢へ及ぼす影響

    釜田 英幸, 平井 公人, 池田 淳史, 伊東 有希, 井手口 英隆, 大森 一弘, 高柴 正悟

    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   158回   34 - 34   2023.5

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    Language:Japanese   Publisher:(NPO)日本歯科保存学会  

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  • 歯内治療が原因で菌血症となった単心室症患者の一症例

    大森 一弘, 杜 徳尚, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 児玉 加奈子, 山本 直史, 赤木 禎治, 笠原 真悟, 伊藤 浩, 高柴 正悟

    日本成人先天性心疾患学会雑誌   12 ( 2 )   30 - 36   2023.5

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    Language:Japanese   Publisher:(一社)日本成人先天性心疾患学会  

    歯科治療は,観血的処置にはみえなくても菌血症を起こすリスクが高い.今回,感染性心内膜炎(IE)高リスクに分類されるフォンタン手術後の患者が歯科治療に起因すると考えられる感染症を起こし,緊急入院に至る症例を経験した.患者は20歳の男性.多脾症候群,右室型単心室に対して,両側両方向性グレン手術とフォンタン手術の手術歴がある.2021年6月,近医で下顎左側第二大臼歯(#37)の慢性根尖性歯周炎の診断のもと,予防的抗菌薬の投与なく歯内治療を開始した.2021年7月,治療中の#37部の自発痛,悪寒,戦慄,発熱を自覚し,当院循環器内科を緊急受診した.履歴から歯性感染が疑われたため,当院歯周科へ緊急紹介され,#37急性根尖性歯周炎と診断した.IE高リスク患者のため緊急入院となり,経験的抗菌療法を開始した.入院5日目,抗菌薬持続投与下で#37の歯内治療を再開,入院12日目に歯内治療を終了,入院13日目に退院した.今回の症例を教訓に,患者自身が歯科治療に先立ち予防的抗菌薬投与の必要性を簡便に提示できる患者カードを作成した.本カードが適切に運用され,歯科治療由来のIE発症リスクが軽減されることを期待する.(著者抄録)

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  • Recent Advances in Apical Periodontitis Treatment: A Narrative Review

    Zulema Arias, Mohammed Zahedul Islam Nizami, Xiaoting Chen, Xinyi Chai, Bin Xu, Canyan Kuang, Kazuhiro Omori, Shogo Takashiba

    Bioengineering   10 ( 4 )   488 - 488   2023.4

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    Publishing type:Research paper (scientific journal)   Publisher:MDPI AG  

    Apical periodontitis is an inflammatory response caused by pulp infection. It induces bone resorption in the apical and periapical regions of the tooth. The most conservative approach to treat this condition is nonsurgical endodontic treatment. However, clinical failure has been reported with this approach; thus, alternative procedures are required. This review highlights recent literature regarding advanced approaches for the treatment of apical periodontitis. Various therapies, including biological medications, antioxidants, specialized pro-resolving lipid mediators, and stem cell therapy, have been tested to increase the success rate of treatment for apical periodontitis. Some of these approaches remain in the in vivo phase of research, while others have just entered the translational research phase to validate clinical application. However, a detailed understanding of the molecular mechanisms that occur during development of the immunoinflammatory reaction in apical periodontitis remains unclear. The aim of this review was to summarize advanced approaches for the treatment of apical periodontitis. Further research can confirm the potential of these alternative nonsurgical endodontic treatment approaches.

    DOI: 10.3390/bioengineering10040488

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  • 歯髄の疼痛抑制に対するレゾルビンD2の効果

    米田 光宏, 井手口 英隆, 中村 心, Chai Xinyi, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   65 ( 春季特別 )   126 - 126   2023.4

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  • 特発性歯肉線維腫症に対して医科歯科連携で包括的に対応した症例の病態考察

    大森 一弘, 河村 麻理, 河野 隆幸, 井手口 英隆, 岸本 晃治, 窪木 拓男, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   65 ( 春季特別 )   161 - 161   2023.4

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  • 妊娠中の体調変化が起因となり重篤化した慢性歯周炎の一症例

    磯島 大地, 井手口 英隆, 大森 一弘, 磯島 修, 高柴 正悟

    日本歯周病学会会誌   65 ( 春季特別 )   167 - 167   2023.4

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  • 歯周炎組織においてADAM17が破骨細胞分化に与える影響

    本行 令奈, 池田 淳史, 井手口 英隆, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   65 ( 春季特別 )   127 - 127   2023.4

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  • 家庭内ストレスが関連した重度慢性歯周炎患者の歯周組織再生療法と病態の考察

    坂井田 京佑, 大森 一弘, 井手口 英隆, 高柴 正悟

    日本歯周病学会会誌   65 ( 春季特別 )   161 - 161   2023.4

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  • The Fungal Metabolite (+)-Terrein Abrogates Inflammatory Bone Resorption via the Suppression of TNF-α Production in a Ligature-Induced Periodontitis Mouse Model

    Hidefumi Sako, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Hidetaka Ideguchi, Saki Yoshimura-Nakagawa, Kyosuke Sakaida, Chiaki Nagata-Kamei, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

    Journal of Fungi   9 ( 3 )   314 - 314   2023.3

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    Current periodontal treatment focuses on the mechanical removal of the source of infection, such as bacteria and their products, and there is no approach to control the host inflammatory response that leads to tissue destruction. In order to control periodontal inflammation, we have previously reported the optimization of (+)-terrein synthesis methods and the inhibitory effect of (+)-terrein on osteoclast differentiation in vitro. However, the pharmacological effect of (+)-terrein in vivo in the periodontitis model is still unknown. In this study, we investigated the effect of synthetic (+)-terrein on inflammatory bone resorption using a ligature-induced periodontitis mouse model. Synthetic (+)-terrein (30 mg/kg) was administered intraperitoneally twice a week to the mouse periodontitis model. The control group was treated with phosphate buffer. One to two weeks after the induction of periodontitis, the periodontal tissues were harvested for radiological evaluation (micro-CT), histological evaluation (HE staining and TRAP staining), and the evaluation of inflammatory cytokine production in the periodontal tissues and serum (quantitative reverse-transcription PCR, ELISA). The synthetic (+)-terrein-treated group suppressed alveolar bone resorption and the number of osteoclasts in the periodontal tissues compared to the control group (p &lt; 0.05). In addition, synthetic (+)-terrein significantly suppressed both mRNA expression of TNF-α in the periodontal tissues and the serum concentration of TNF-α (both p &lt; 0.05). In conclusion, we have demonstrated that synthetic (+)-terrein abrogates alveolar bone resorption via the suppression of TNF-α production and osteoclast differentiation in vivo. Therefore, we could expect potential clinical effects when using (+)-terrein on inflammatory bone resorption, including periodontitis.

    DOI: 10.3390/jof9030314

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  • Autophagy as a potential mechanism underlying the biological effect of 1,25-Dihydroxyvitamin D3 on periodontitis: a narrative review. International journal

    Xiaoting Chen, Zulema Arias, Kazuhiro Omori, Tadashi Yamamoto, Yuki Shinoda-Ito, Shogo Takashiba

    BMC oral health   23 ( 1 )   90 - 90   2023.2

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    The major active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3), is known for its wide bioactivity in periodontal tissues. Although the exact mechanisms underlying its protective action against periodontitis remain unclear, recent studies have shown that 1,25D3 regulates autophagy. Autophagy is vital for intracellular pathogen invasion control, inflammation regulation, and bone metabolic balance in periodontal tissue homeostasis, and its regulation could be an interesting pathway for future periodontal studies. Since vitamin D deficiency is a worldwide health problem, its role as a potential regulator of autophagy provides new insights into periodontal diseases. Based on this premise, this narrative literature review aimed to investigate the possible connection between 1,25D3 and autophagy in periodontitis. A comprehensive literature search was conducted on PubMed using the following keywords (e.g., vitamin D, autophagy, periodontitis, pathogens, epithelial cells, immunity, inflammation, and bone loss). In this review, the latest studies on the protective action of 1,25D3 against periodontitis and the regulation of autophagy by 1,25D3 are summarized, and the potential role of 1,25D3-activated autophagy in the pathogenesis of periodontitis is analyzed. 1,25D3 can exert a protective effect against periodontitis through different signaling pathways in the pathogenesis of periodontitis, and at least part of this regulatory effect is achieved through the activation of the autophagic response. This review will help clarify the relationship between 1,25D3 and autophagy in the homeostasis of periodontal tissues and provide perspectives for researchers to optimize prevention and treatment strategies in the future.

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  • A case report of bacteremia caused by dental endodontic treatment in a patient with single ventricle Reviewed

    Kazuhiro Omori, Norihisa Toh, Hidetaka Ideguchi, Kentaro Okamoto, Hidefumi Sako, Kanako Kodam, Tadashi Yamamoto, Teiji Akagi, Shingo Kasahara, Hiroshi Ito, Shogo Takashib

    12 ( 2 )   1 - 8   2023.2

  • Periodontal diseases assessed by average bone resorption are associated with microvascular complications in patients with type 2 diabetes.

    Noriko Sugi, Eri Eguchi, Ayaka Tsuboi, Kazu Hatanaka, Shogo Takashiba, Yuri Kira, Masako Miura, Keiki Ogino, Keita Hirano, Takahiko Nakagawa, Kentaro Doi

    Diabetology international   14 ( 1 )   32 - 39   2023.1

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    UNLABELLED: Periodontal disease often develops in patients with diabetes, and further exacerbated with diabetic complications. It would be clinically important to clarify the relationship between diabetic microvascular diseases and periodontal disease. This study aimed to evaluate the association between periodontal disease and diabetic complications in patients with type 2 diabetes with poor glycemic control. A total of 447 patients with type 2 diabetes hospitalized at Rakuwakai Otowa Hospital, Japan, were initially recruited in this study. After excluding 134 patients who lacked clinical data or were edentulous, 312 were included in our study. The severity of periodontal disease was evaluated based on the average bone resorption rate. Patients with diabetic nephropathy developed severe periodontal disease (multivariate-adjusted odds ratio, 3.00 [95% CI 1.41-5.19]). Diabetic neuropathy was positively associated with the severity of periodontal disease; the multivariate-adjusted odds ratio (95% CI) was 1.62 (0.87‒2.99) for moderate and 4.26 (2.21‒8.20) for severe periodontal disease. In contrast, diabetic retinopathy was linked with moderate periodontal disease (multivariate-adjusted odds ratio 2.23 [95% CI 1.10-4.10]), but not with severe conditions (multivariate-adjusted odds ratio 0.92 [95% CI 0.67-3.07]). In conclusion, periodontal disease, evaluated by average bone resorption rate, was associated with diabetic nephropathy and neuropathy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-022-00591-0.

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  • Reattachment of Fractured Tooth Fragment by Multidisciplinary Treatment Approach

    Zulema Arias, Heber Falú Hinojosa Ledezma, Claudia Patricia Osorio Terán, Kazuhiro Omori, Tadashi Yamamoto, Mohammed Zahedul Islam Nizami, Shogo Takashiba

    The Bulletin of Tokyo Dental College   2023

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    DOI: 10.2209/tdcpublication.2022-0019

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  • Graphene Oxide-based Endodontic Sealer: An in Vitro Study.

    Mohammed Zahedul Islam Nizami, Melahat Gorduysus, Yuki Shinoda-Ito, Tadashi Yamamoto, Yuta Nishina, Shogo Takashiba, Zulema Arias

    Acta medica Okayama   76 ( 6 )   715 - 721   2022.12

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    The failure of endodontic treatment is directly associated with microbial infection in the root canal or periapical areas. An endodontic sealer that is both bactericidal and biocompatible is essential for the success of root canal treatments. This is one of the vital issues yet to be solved in clinical dental practice. This in vitro study assessed the effectiveness of graphene oxide (GO) composites GO-CaF2 and GO-Ag-CaF2 as endodontic sealer materials. Dentin slices were coated with either the GO-based composites or commonly used root canal sealers (non-eugenol zinc oxide sealer). The coated slices were treated in 0.9% NaCl, phosphate-buffered saline (PBS), and simulated body fluid (SBF) at 37˚C for 24 hours to compare their sealing effect on the dentin surface. In addition, the radiopacity of these composites was examined to assess whether they complied with the requirements of a sealer for good radiographic visualization. Scanning electron microscopy showed the significant sealing capability of the composites as coating materials. Radiographic images confirmed their radiopacity. Mineral deposition indicated their bioactivity, especially of GO-Ag-CaF2, and thus it is potential for regenerative application. They were both previously shown to be bactericidal to oral microbes and cytocompatible with host cells. With such a unique assemblage of critical properties, these GO-based composites show promise as endodontic sealers for protection against reinfection in root canal treatment and enhanced success in endodontic treatment overall.

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  • 酸化グラフェンと塩化セチルピリジニウムを応用した不織布マスクの抗菌性

    越宗 朋隆, 伊東 有希[信田], 仁科 勇太, 高柴 正悟

    岡山歯学会雑誌   41 ( 2 )   60 - 61   2022.12

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  • オートファジー ビタミンDが歯周炎に及ぼす生物学的効果の潜在的メカニズム

    Chen Xiaoting, Arias Zulema, 大森 一弘, 山本 直史, 伊東 有希[信田], 高柴 正悟

    岡山歯学会雑誌   41 ( 2 )   60 - 60   2022.12

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  • 岡山大学病院歯科・歯周科部門での歯周組織再生療法におけるリグロス歯科用液キット導入の影響

    松本 俊樹, 井手口 英隆, 大森 一弘, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   41 ( 2 )   59 - 60   2022.12

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  • Periodontal Treatment and Usual Care for Nonalcoholic Fatty Liver Disease: A Multicenter, Randomized Controlled Trial. Reviewed International journal

    Yohei Kamata, Takaomi Kessoku, Tomoko Shimizu, Satsuki Sato, Takashi Kobayashi, Takeo Kurihashi, Toshiya Morozumi, Tomoyuki Iwasaki, Shogo Takashiba, Kazu Hatanaka, Nobushiro Hamada, Toshiro Kodama, Takuma Higurashi, Masataka Taguri, Masato Yoneda, Haruki Usuda, Koichiro Wada, Atsushi Nakajima, Masato Minabe

    Clinical and translational gastroenterology   13 ( 11 )   e00520   2022.11

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    BACKGROUND: Periodontal disease is associated with non-alcoholic fatty liver disease (NAFLD). We evaluated periodontal treatment efficacy in patients with NAFLD and periodontal disease. METHODS: This multicenter, 2-arm, randomized study recruited adult patients with NAFLD and periodontitis, alanine aminotransferase levels ≥40 U/L, and equivalent steatosis grade ≥1. Forty eligible patients (18 men and 22 women) were randomly assigned to 2 groups (scaling and root planning [SRP; n = 20] and tooth-brushing [n = 20] groups) stratified by age and sex. The primary and secondary endpoints were changes in alanine aminotransferase levels and serum Porphyromonas gingivalis IgG-antibody titers from baseline to 12 weeks, respectively. Efficacy analysis was performed using an intention-to-treat approach (t-test). This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMINXXXXXXX). RESULTS: We observed a significantly higher decrease in absolute alanine aminotransferase levels and P. gingivalis IgG-antibody titers in the SRP group than in the tooth-brushing group (-12 vs 1 U/L; mean difference [δ], -12; 95% confidence interval [CI], -20 to -5; P = 0.002). The decrease in P. gingivalis IgG-antibody titer was significantly higher in the SRP group than in the tooth-brushing group (FDC381, -1.6 [2.5]; δ, -1.6; 95% CI, -2.7 to -0.4; P = 0.0092; SU63, -1.7 [2.0]; δ, -1.7; 95% CI, -2.7 to -0.7). No life-threatening events or treatment-related deaths occurred. CONCLUSION: Periodontal treatment induced significant short- and mid-term reductions in liver enzyme levels and antibody titers. Further research is warranted to clearly define SRP efficacy and tolerability in patients with NAFLD and periodontitis.

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  • ベーチェット病を併発したLigneous歯周炎患者の包括的な検査・診断症例

    平井 杏奈, 伊東 有希[信田], 井手口 英隆, 大森 一弘, 山本 直史, 高柴 正悟

    日本口腔検査学会総会・学術大会プログラム・抄録集   15回   70 - 70   2022.11

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  • A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease Reviewed

    Satsuki Sato, Yohei Kamata, Takaomi Kessoku, Tomoko Shimizu, Takashi Kobayashi, Takeo Kurihashi, Shogo Takashiba, Kazu Hatanaka, Nobushiro Hamada, Toshiro Kodama, Takuma Higurashi, Masataka Taguri, Masato Yoneda, Haruki Usuda, Koichiro Wada, Atsushi Nakajima, Toshiya Morozumi, Masato Minabe

    Scientific Reports   12 ( 1 )   2022.8

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    Abstract

    The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonasgingivalis infection is a risk factor for systemic diseases. We investigated the association of P.gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P.gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P.gingivalis positivity (P.gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p &lt; 0.0001). A P.gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P.gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had &gt; 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.

    DOI: 10.1038/s41598-022-17917-2

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    Other Link: https://www.nature.com/articles/s41598-022-17917-2

  • Treatment resistance of rheumatoid arthritis relates to infection of periodontal pathogenic bacteria: a case-control cross-sectional study. Reviewed International journal

    Kazu Takeuchi-Hatanaka, Yoshinobu Koyama, Kentaro Okamoto, Kyosuke Sakaida, Tadashi Yamamoto, Shogo Takashiba

    Scientific reports   12 ( 1 )   12353 - 12353   2022.7

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    Recent studies have shown that periodontitis is associated with rheumatoid arthritis (RA) and periodontal bacteria, such as Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are involved in the pathogenesis of RA via citrullinated proteins. Smoking has also been shown to be involved in the pathogenesis of RA; however, the extent of this involvement is still poorly understood. In addition, RA and polymyalgia rheumatica (PMR) are sometimes difficult to differentiate; however, the relationship between PMR and the factors from smoking and periodontal bacteria is unclear. The aim of this study was to clarify the relationship between periodontal pathogenic bacterial infections and smoking in patients with RA or PMR. This case-control study included 142 patients with untreated RA or PMR. This study evaluated the serum antibody titers against periodontal pathogenic bacterial antigens and an anti-citrullinated peptide antibody (ACPA). In patients with RA, the relationship between antibody titers and disease activity of RA and response after 3 months of treatment was also investigated. Additionally, the effects of smoking were evaluated. Although there was no significant difference in serum antibody titer against periodontal pathogenic bacteria between the ACPA-positive RA group and the ACPA-negative PMR group, we found an association between the elevated antibody titer against Pg and the degree of ACPA value, especially between negative group and high-value positive group (≥ 100 U/mL). The antibody titers against Aa and Pg did not differ depending on disease activity score 28 (DAS28) at baseline; however, patients with high antibody titers had poor RA therapeutic response as judged by DAS28 after 3 months. We could not find any association between smoking and any of these parameters. Periodontal pathogenic bacteria, especially Pg, are associated with elevated ACPA levels. Our findings suggest that Pg and Aa infections interfere with the therapeutic response of RA.

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  • Analysis of subgingival microbiota in monozygotic twins with different severity and progression risk of periodontitis. Reviewed International journal

    Tadashi Yamamoto, Makoto Taniguchi, Kazuyuki Matsunaga, Yusuke Kawata, Mari Kawamura, Keisuke Okubo, Keisuke Yamashiro, Kazuhiro Omori, Shogo Takashiba

    Clinical case reports   10 ( 4 )   e05725   2022.4

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    The study aims to reveal the composition of subgingival bacteria in monozygotic twins with discordant in severity and progression risk of periodontitis. Microbiome analysis indicated that most bacteria were heritable but differed in their abundance and immune response. The dysbiotic bacteria can be considered as risk markers for periodontitis progression.

    DOI: 10.1002/ccr3.5725

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  • Estimation of periodontal pocket surface area in small to medium dogs: a proof-of-concept study. Reviewed International journal

    Kazuya Tamura, Masako Tokuzen-Tai, Yasir Dilshad Siddiqui, Hitomi Tamura-Naito, Yoshiharu Nagahara, Kazu Hatanaka-Takeuchi, Tadashi Yamamoto, Shogo Takashiba

    BMC veterinary research   18 ( 1 )   13 - 13   2022.1

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    BACKGROUND: Periodontal disease is the most common dental disease in dogs. Although the systemic effects of periodontal disease have not been clarified in veterinary science, it is necessary to evaluate the effects of periodontal disease in clinical trials in the future. There have been a few clinical attempts made, however, to assess the severity of periodontal inflammation and its impact on the systemic health of dogs. Meanwhile, in the field of dentistry for humans, the periodontal inflamed surface area (PISA) and periodontal epithelial surface area (PESA) have been used to quantitatively assess the degree of periodontal disease affecting a single tooth as well as the overall extent of periodontitis. Recent studies have also suggested the use of these assessments to examine the relationship between periodontal inflammation and systemic health. RESULTS: The estimation formula for a dog's periodontal pocket surface area (PPSA), an alternative to PISA and PESA in humans, was established using body weight and periodontal pocket depth. Actual values were measured using extracted teeth from various dog breeds and sizes (2.3-25.0 kg of body weight) to obtain universal regression equations for PPSA. Altogether, 625 teeth from 73 dogs of 16 breeds were extracted and subsequently analyzed for morphological information. PPSA was measured in 61 dogs of 10 breeds with periodontal disease using the established estimation formulas, and the correlation between PPSA and preoperative blood chemistry data was analyzed accordingly. A strong correlation was found between PPSA and serum globulin (r = 0.71) while moderate correlations were found for C-reactive protein (r = 0.54) and serum albumin (r = -0.51). CONCLUSIONS: Estimation formulas using body weight and the 6-point probing depth were established for determining PPSA. Direct correlations between PPSA and several blood test results were observed in the study sample. Taken together, these results suggest that PPSA could be useful for evaluating the effects of periodontitis on systemic conditions in dogs.

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  • Enzymatic measurement of short-chain fatty acids and application in periodontal disease diagnosis. Reviewed International journal

    Kazu Hatanaka, Yasushi Shirahase, Toshiyuki Yoshida, Mari Kono, Naoki Toya, Shin-Ichi Sakasegawa, Kenji Konishi, Tadashi Yamamoto, Kuniyasu Ochiai, Shogo Takashiba

    PloS one   17 ( 7 )   e0268671   2022

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    Periodontal disease is a chronic inflammatory condition caused by periodontal pathogens in the gingival sulcus. Short-chain fatty acids (SCFAs) produced by causal bacteria are closely related to the onset and progression of periodontal disease and have been reported to proliferate in the periodontal sulcus of patients experiencing this pathology. In such patients, propionic acid (C3), butyric acid (C4), isobutyric acid (IC4), valeric acid (C5), isovaleric acid (IC5), and caproic acid (C6), henceforth referred to as [C3-C6], has been reported to have a detrimental effect, while acetic acid (C2) exhibits no detrimental effect. In this study, we established an inexpensive and simple enzymatic assay that can fractionate and measure these acids. The possibility of applying this technique to determine the severity of periodontal disease by adapting it to specimens collected from humans has been explored. We established an enzyme system using acetate kinase and butyrate kinase capable of measuring SCFAs in two fractions, C2 and [C3-C6]. The gingival crevicular fluid (GCF) and saliva of 10 healthy participants and 10 participants with mild and severe periodontal disease were measured using the established enzymatic method and conventional gas chromatography-mass spectrometry (GC-MS). The quantification of C2 and [C3-C6] in human GCF and saliva was well correlated when using the GC-MS method. Furthermore, both C2 and [C3-C6] in the GCF increased with disease severity. However, while no significant difference was observed between healthy participants and periodontal patients when using saliva, [C3-C6] significantly differed between mild and severe periodontal disease. The enzymatic method was able to measure C2 and [C3-C6] separately as well as using the GC-MS method. Furthermore, the C2 and [C3-C6] fractions of GCF correlated with disease severity, suggesting that this method can be applied clinically. In contrast, the quantification of C2 and [C3-C6] in saliva did not differ significantly between healthy participants and patients with periodontal disease. Future studies should focus on inflammation rather than on tissue destruction.

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  • 不妊治療中患者における歯周病原細菌の感染度調査 血清IgG抗体価検査を応用したパイロット研究

    永田 千晶, 大森 一弘, 佐光 秀文, 坂井田 京佑, 井手口 英隆, 池田 淳史, 徳善 真砂子, 平井 公人, 畑中 加珠, 山本 直史, 滝川 雅之, 三宅 貴仁, 高柴 正悟

    日本未病学会学術総会抄録集   28回   106 - 106   2021.11

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  • Use of Highly Accurate Devices for a First Lower Premolar Endodontic Treatment with Multiple Root Canals. Reviewed International coauthorship

    Zulema Arias Martinez, Jorge Lopez Videla, Keisuke Yamashiro, Yuki Shinoda-Ito, Tadashi Yamamoto, Shogo Takashiba

    Acta medica Okayama   75 ( 5 )   641 - 645   2021.10

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    This case report highlights the importance of using a dental operating microscope (DOM) and ultrasonic endodontic tips (UETs) to locate all root canals in the lower first premolar. A 53-year-old woman presented to our clinic with pain in the lower right first premolar. After a detailed search using a DOM and UETs, three root canals were found, prepared with rotary HyFlex endodontic files, and obturated using the lateral condensation technique. At the five-year follow-up after treatment, the tooth was completely restored and fulfilling its function, with no signs or symptoms of any post-treatment flare-up.

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  • 歯周感染が子宮組織に及ぼす影響のマウス絹糸結紮歯周炎モデルにおける免疫学的検討

    永田 千晶, 大森 一弘, 井手口 英隆, 佐光 秀文, 坂井田 京佑, 徳善 真砂子, 平井 公人, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   63 ( 秋季特別 )   118 - 118   2021.10

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  • 歯内治療が原因で菌血症となった単心室症患者の症例報告とその対応策の提案

    児玉 加奈子, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 松本 俊樹, 大森 一弘, 山本 直史, 高柴 正悟

    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   155回   112 - 112   2021.10

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  • Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation. Reviewed International journal

    Yao Zhang, Hidetaka Ideguchi, Hiroaki Aoyagi, Keisuke Yamashiro, Tadashi Yamamoto, Masahiro Nishibori, Shogo Takashiba

    International immunopharmacology   96   107772 - 107772   2021.7

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    Malnutrition causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern that is present in the nuclei of macrophages and is secreted into the extracellular milieu in response to stimuli. It stimulates the production of interleukin-1β (IL-1β) through the receptors for advanced glycation end products (RAGE), inducing an inflammatory response, which is an essential response to initiate wound healing. We hypothesized that malnutrition may interfere with this cascade, causing abnormal inflammation and ultimately delaying wound healing. We used tooth-extracted mice with malnutrition fed with low-casein diet for two weeks. On days 3 and 7 after tooth extraction, the wound tissue was histologically observed and analyzed for several factors in the inflammation-regeneration lineage, including IL-1β, mesenchymal stem cells, myeloperoxidase activity, HMGB1, macrophage polarization, and adenosine 5-triphosphate (ATP). On day 7, delayed wound healing was observed with the following findings under malnutrition conditions: decreased mRNA expression of genes for regeneration and mesenchymal stem cell (MSC) accumulation, an obvious increase in myeloperoxidase and IL-1β mRNA expression, an increase in HMGB1 levels, and an increase in ATP concentration in tissues with elevated proportion of M2 macrophages. These results suggest that the significantly increased secretion of HMGB1 associated with the upregulated production of ATP and IL-1β secretion via the RAGE pathway may interfere with the resolution of inflammation and wound healing under the state of malnutrition.

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  • The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C α/βII Phosphorylation. Reviewed International journal

    Kyosuke Sakaida, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Saki Nakagawa, Hidefumi Sako, Chiaki Kamei, Satoshi Yamamoto, Hiroya Kobayashi, Satoki Ishii, Mitsuaki Ono, Soichiro Ibaragi, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

    Frontiers in pharmacology   12   674366 - 674366   2021.6

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    Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKCα/βII, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis.

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  • Association between Psychosocial Factors and Oral Symptoms among Residents in Fukushima after the Great East Japan Earthquake: A Cross-Sectional Study from the Fukushima Health Management Survey. Reviewed International journal

    Narumi Funakubo, Ayaka Tsuboi, Eri Eguchi, Fumikazu Hayashi, Masaharu Maeda, Hirooki Yabe, Seiji Yasumura, Kenji Kamiya, Shogo Takashiba, Tetsuya Ohira, Mental Health Group Of The Fukushima Health Management Survey

    International journal of environmental research and public health   18 ( 11 )   2021.6

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    Oral health is closely related to subjective general health and systemic diseases. This cross-sectional study aimed to identify the factors related to oral symptoms and their worsening in relation to psychosocial factors after the Great East Japan Earthquake. In this study, 64,186 residents aged 15-101 years old, who experienced the earthquake on 11 March 2011, were surveyed regarding their oral symptoms; psychological factors, such as post-traumatic reactions and psychological distress; and social factors such as evacuation, work change, and loss of a close person; history of systemic diseases; and lifestyle. Binomial logistic regression analysis was used to calculate odds ratios, and 95% confidence intervals were established for each factor associated with prevalent and exacerbated oral symptoms. The proportions of participants with prevalent and exacerbated oral symptoms were 10.3% and 1.6%, respectively. The multivariate odds ratios and 95% CI of psychosocial factors associated with exacerbated oral symptoms were as follows: post-traumatic stress disorder symptoms, 2.24 (1.64-3.06); work changes, 1.88 (1.34-2.65); history of dyslipidemia, 1.74 (1.27-2.39); and subjective current poor health condition, 2.73 (2.00-3.75). Psychological factors, social factors, and physical factors were associated with both prevalent and exacerbated oral symptoms.

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  • Prospective Longitudinal Changes in the Periodontal Inflamed Surface Area Following Active Periodontal Treatment for Chronic Periodontitis. Reviewed International journal

    Yoshiaki Nomura, Toshiya Morozumi, Atsushi Saito, Atsutoshi Yoshimura, Erika Kakuta, Fumihiko Suzuki, Fusanori Nishimura, Hideki Takai, Hiroaki Kobayashi, Kazuyuki Noguchi, Keiso Takahashi, Koichi Tabeta, Makoto Umeda, Masato Minabe, Mitsuo Fukuda, Naoyuki Sugano, Nobuhiro Hanada, Nobuo Yoshinari, Satoshi Sekino, Shogo Takashiba, Soh Sato, Toshiaki Nakamura, Tsutomu Sugaya, Yohei Nakayama, Yorimasa Ogata, Yukihiro Numabe, Taneaki Nakagawa

    Journal of clinical medicine   10 ( 6 )   2021.3

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    Periodontal disease is a chronic inflammatory disease of the periodontal tissue. The periodontal inflamed surface area (PISA) is a proposed index for quantifying the inflammatory burden resulting from periodontitis lesions. This study aimed to investigate longitudinal changes in the periodontal status as evaluated by the PISA following the active periodontal treatment. To elucidate the prognostic factors of PISA, mixed-effect modeling was performed for clinical parameters, tooth-type, and levels of periodontal pathogens as independent variables. One-hundred-twenty-five patients with chronic periodontitis who completed the active periodontal treatment were followed-up for 24 months, with evaluations conducted at 6-month intervals. Five-times repeated measures of mean PISA values were 130+/-173, 161+/-276, 184+/-320, 175+/-417, and 209+/-469 mm2. Changes in clinical parameters and salivary and subgingival periodontal pathogens were analyzed by mixed-effect modeling. Plaque index, clinical attachment level, and salivary levels of Porphyromonas gingivalis were associated with changes in PISA at the patient- and tooth-level. Subgingival levels of P. gingivalis and Prevotella intermedia were associated with changes in PISA at the sample site. For most patients, changes in PISA were within 10% of baseline during the 24-month follow-up. However, an increase in the number of bleeding sites in a tooth with a deep periodontal pocket increased the PISA value exponentially.

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  • Estimation of the Periodontal Inflamed Surface Area by Simple Oral Examination. Reviewed International journal

    Yoshiaki Nomura, Toshiya Morozumi, Yukihiro Numabe, Yorimasa Ogata, Yohei Nakayama, Tsutomu Sugaya, Toshiaki Nakamura, Soh Sato, Shogo Takashiba, Satoshi Sekino, Nobuo Yoshinari, Nobuhiro Hanada, Naoyuki Sugano, Mitsuo Fukuda, Masato Minabe, Makoto Umeda, Koichi Tabeta, Keiso Takahashi, Kazuyuki Noguchi, Hiroaki Kobayashi, Hideki Takai, Fusanori Nishimura, Fumihiko Suzuki, Erika Kakuta, Atsutoshi Yoshimura, Atsushi Saito, Taneaki Nakagawa

    Journal of clinical medicine   10 ( 4 )   2021.2

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    The periodontal inflamed surface area (PISA) is a useful index for clinical and epidemiological assessments, since it can represent the inflammation status of patients in one contentious variable. However, calculation of the PISA is difficult, requiring six point probing depth measurements with or without bleeding on probing on 28 teeth, followed by data input in a calculation program. More simple methods are essential for screening periodontal disease or in epidemiological studies. In this study, we tried to establish a convenient partial examination method to estimate PISA. Cross-sectional data of 254 subjects who completed active periodontal therapy were analyzed. Teeth that represent the PISA value were selected by an item response theory approach. The maxillary second molar, first premolar, and lateral incisor and the mandibular second molar and lateral incisor were selected. The sum of the PISAs of these teeth was significantly correlated with the patient's PISA (R2 = 0.938). More simply, the sum of the maximum values of probing pocket depth with bleeding for these teeth were also significantly correlated with the patient's PISA (R2 = 0.6457). The simple model presented in this study may be useful to estimate PISA.

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  • Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis. Reviewed International journal

    Daichi Isoshima, Keisuke Yamashiro, Kazuyuki Matsunaga, Makoto Taniguchi, Takehiro Matsubara, Shuta Tomida, Shinzo Ota, Michiyoshi Sato, Yutaka Shimoe, Tatsuo Kohriyama, Zulema Arias, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

    Odontology   109 ( 1 )   239 - 249   2021.1

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    There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly.

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  • Allergic Reaction to Zirconia Ceramic Bridge Cementation Using a Dental Adhesive Resin Cement: a Case Report Reviewed International journal

    Keisuke Yamashiro, Haruna Miki, Masae Kitagawa, Hiroko Oka, Zulema Arias, Shogo Takashiba

    SN Comprehensive Clinical Medicine   3 ( 1 )   327 - 330   2021.1

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  • Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model. Reviewed International journal

    Yoshiaki Nomura, Toshiya Morozumi, Mitsuo Fukuda, Nobuhiro Hanada, Erika Kakuta, Hiroaki Kobayashi, Masato Minabe, Toshiaki Nakamura, Yohei Nakayama, Fusanori Nishimura, Kazuyuki Noguchi, Yukihiro Numabe, Yorimasa Ogata, Atsushi Saito, Soh Sato, Satoshi Sekino, Naoyuki Sugano, Tsutomu Sugaya, Fumihiko Suzuki, Keiso Takahashi, Hideki Takai, Shogo Takashiba, Makoto Umeda, Hiromasa Yoshie, Atsutoshi Yoshimura, Nobuo Yoshinari, Taneaki Nakagawa

    Journal of clinical medicine   9 ( 11 )   2020.11

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    Periodontal examination data have a complex structure. For epidemiological studies, mass screenings, and public health use, a simple index that represents the periodontal condition is necessary. Periodontal indices for partial examination of selected teeth have been developed. However, the selected teeth vary between indices, and a justification for the selection of examination teeth has not been presented. We applied a graded response model based on the item response theory to select optimal examination teeth and sites that represent periodontal conditions. Data were obtained from 254 patients who participated in a multicenter follow-up study. Baseline data were obtained from initial follow-up. Optimal examination sites were selected using item information calculated by graded response modeling. Twelve sites-maxillary 2nd premolar (palatal-medial), 1st premolar (palatal-distal), canine (palatal-medial), lateral incisor (palatal-central), central incisor (palatal-distal) and mandibular 1st premolar (lingual, medial)-were selected. Mean values for clinical attachment level, probing pocket depth, and bleeding on probing by full mouth examinations were used for objective variables. Measuring the clinical parameters of these sites can predict the results of full mouth examination. For calculating the periodontal index by partial oral examination, a justification for the selection of examination sites is essential. This study presents an evidence-based partial examination methodology and its modeling.

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  • Follistatin expressed in mechanically-damaged salivary glands of male mice induces proliferation of CD49f+ cells. Reviewed International journal

    A Ikeda, T Yamamoto, J Mineshiba, S Takashiba

    Scientific reports   10 ( 1 )   19959 - 19959   2020.11

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    Salivary glands (SGs) are very important for maintaining the physiological functions of the mouth. When SGs regenerate and repair from various damages, including mechanical, radiological, and immune diseases, acinar and granular duct cells originate from intercalated duct cells. However, the recovery is often insufficient because of SGs' limited self-repair function. Furthermore, the precise repair mechanism has been unclear. Here, we focused on CD49f, one of the putative stem cell markers, and characterized CD49f positive cells (CD49f+ cells) isolated from male murine SGs. CD49f+ cells possess self-renewal ability and express epithelial and pluripotent markers. Compared to CD49f negative cells, freshly isolated CD49f+ cells highly expressed inhibin beta A and beta B, which are components of activin that has anti-proliferative effects. Notably, an inhibitor of activin, follistatin was expressed in mechanically-damaged SGs, meanwhile no follistatin was expressed in normal SGs in vivo. Moreover, sub-cultured CD49f+ cells highly expressed both Follistatin and a series of proliferative genes, expressions of which were decreased by Follistatin siRNA. These findings indicated that the molecular interaction between activin and follistatin may induce CD49f+ cells proliferation in the regeneration and repair of mouse SGs.

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  • Isolation and identification of the antimicrobial substance included in tempeh using Rhizopus stolonifer NBRC 30816 for fermentation. Reviewed International journal

    Masahiro Ito, Takashi Ito, Hideyuki Aoki, Koshi Nishioka, Tsugumi Shiokawa, Hiroko Tada, Yuki Takeuchi, Nobuyuki Takeyasu, Tadashi Yamamoto, Shogo Takashiba

    International journal of food microbiology   325   108645 - 108645   2020.7

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    In this study, we focus on the antimicrobial properties of tempeh, a soybean fermented food, against oral bacteria. Tempeh showed antimicrobial activity against dental caries pathogenic bacterium Streptococcus mutans at a final concentration of 1 mg/mL. An antimicrobial substance contained in tempeh was present in the 100 kDa or greater fraction generated by ultrafiltration, but it was found not to be proteinaceous by native-PAGE, SDS-PAGE and protein degradation tests. Next, when the fraction was purified with an ODS column, the 80% and 100% methanol eluates showed antimicrobial activity against S. mutans. The 100% methanol eluate was further subjected to a 2nd column purification, and isolation of the target was confirmed by HPLC. When the isolated material was analyzed by ESI-MS, the m/z was 279.234. Further analysis by Raman spectroscopy revealed a peak similar to linoleic acid. This substance also possessed antimicrobial properties equivalent to linoleic acid.

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  • Simultaneous Determination of 7 Short-Chain Fatty Acids in Human Saliva by High-Sensitivity Gas Chromatography-Mass Spectrometry Reviewed

    Takahiro KAWASE, Kazu HATANAKA, Mari KONO, Yasushi SHIRAHASE, Kuniyasu OCHIAI, Shogo TAKASHIBA, Takamitsu TSUKAHARA

    CHROMATOGRAPHY   41 ( 2 )   63 - 71   2020.6

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    DOI: 10.15583/jpchrom.2019.025

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  • Identification and Modification of Porphyromonas gingivalis Cysteine Protease, Gingipain, Ideal for Screening Periodontitis. Reviewed International journal

    Kimito Hirai, Tomoko Yamaguchi-Tomikawa, Toru Eguchi, Hiroshi Maeda, Shogo Takashiba

    Frontiers in immunology   11   1017 - 1017   2020.6

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    Chronic periodontitis is an inflammatory disease caused by the formation of oral microbial biofilms. Periodontitis is associated with general health and not only oral diseases. Porphyromonas gingivalis is a well-known keystone pathogen for periodontitis and is associated with several systemic diseases, such as diabetes mellitus and Alzheimer's disease. We previously developed a system for screening periodontitis using P. gingivalis-specific serum immunoglobulin G (IgG) in an enzyme-linked immunosorbent assay with a sensitivity of 0.774 and a specificity of 0.586 and an area under the receiver operating characteristic curve of 0.708. However, the antigens elicited non-specific responses, since they were obtained from whole extracts of sonicated cultured bacteria. The purpose of this study was to identify antigens ideal for a sensitive and specific serum test. We identified the specific antigens using immunoaffinity columns immobilized with IgG antibodies from periodontitis patients. Liquid chromatography-tandem mass spectrometry identified 29 antigens from the elutes. Recombinant proteins for these candidates were synthesized using the wheat germ cell-free translation system and screened by dot blot analysis with serum from the columns. Three of the 16 candidates that reacted showed strongest affinities upon dot blot analysis; they included outer membrane protein 28, cysteine proteases, lysine gingipain Kgp, and arginine gingipain RgpA. Outer membrane protein 28 was not suitable for screening P. gingivalis infection because of its high false-negative rates. Kgp and RgpA were unstable antigens since they underwent self-digestion. They were made stable by substituting the active cysteine residues in Kgp and RgpA with alanine using site-directed mutagenesis. Using the modified antigens, we demonstrated that the patient serum IgG level against RgpA was the highest among all the antigens expressed in P. gingivalis. Moreover, the N-terminus of recombinant RgpA was excellent in differentiating between diseased and non-diseased states (with sensitivity of 0.85, specificity of 0.9, and area under the curve of 0.915). Although dot blot analysis was the only experiment used, the N-terminus of RgpA is an excellent antigen to immunologically test for P. gingivalis infection, especially for estimating the risks for periodontitis-associated systemic diseases. In conclusion, we have developed a P. gingivalis antigen for screening periodontitis.

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  • The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1. Reviewed International journal

    Saki Nakagawa, Kazuhiro Omori, Masaaki Nakayama, Hiroki Mandai, Satoshi Yamamoto, Hiroya Kobayashi, Hidefumi Sako, Kyosuke Sakaida, Hiroshi Yoshimura, Satoki Ishii, Soichiro Ibaragi, Kimito Hirai, Keisuke Yamashiro, Tadashi Yamamoto, Seiji Suga, Shogo Takashiba

    International immunopharmacology   83   106429 - 106429   2020.6

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    Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease.

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  • Evaluation of the simulator with automatic irrigation control system designed for countermeasures of internal contamination in dental unit water lines. Reviewed International journal

    Keisuke Okubo, Takashi Ito, Kentaro Okamoto, Ichiro Yamamoto, Hajime Mizutani, Yusuke Kawata, Yasuyoshi Shiota, Masahiro Ito, Shin Nakamura, Masako Tai, Tadashi Yamamoto, Shogo Takashiba

    Heliyon   6 ( 6 )   e04132   2020.6

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    The prevention of nosocomial infections is an imperative task. The dental chair unit (DCU) is an indispensable device used in dental treatment. However, it is known that the dental unit water line (DUWL) can become contaminated with biofilm, consisting mainly of heterotrophic bacteria (HB). Recently, the International Organization for Standardization specified the methods for testing DUWL contamination management. On these grounds, a simulator reproducing DUWL was prepared to standardize the examination method of the DUWL contamination. Objectives: To evaluate the reproducibility of the DUWL simulator, monitor the DUWL contamination states, and test the efficacy of a commercial decontaminant for DUWL. Methods: The DUWL simulator was assembled by a DCU manufacturing company. The simulator's DUWL was filled with tap water (TW), and left for approximately one year. Neutral electrolyzed water (NEW) was used as a decontaminant for DUWL. Both TW and NEW were passed through DUWL in a timely manner simulating daily dental treatment. Water was sampled from the air turbine hand piece weekly for 4 weeks and used for HB culture. Contamination status was evaluated by measuring bacterial adenosine triphosphate release and by culturing on Reasoner's 2A medium. Results: The DUWL released contaminated water had a bacterial count of over 6 × 104 cfu/mL. After passing NEW through DUWL for 1 week, the count drastically decreased to its basal level and remained steady for 4 weeks. However, TW showed no effect on DUWL decontamination throughout the examination periods. Conclusions: The DUWL simulator could be useful to examine the efficacy of the decontaminant for DUWL and development of new methods in DUWL contamination management.

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  • Graphene oxide: A new direction in dentistry Reviewed International journal

    Mohammed Zahedul Islam Nizami, Shogo Takashiba, Yuta Nishina

    Applied Materials Today   19   100576   2020.6

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    This inclusive review summarizes the recent advances in the application of graphene oxide (GO) and functionalized GO in oral and dental research. GO possesses several extraordinary physical, chemical, optical, electrical, and mechanical properties. Because of its high surface area and oxygenated functional groups, GO exhibits excellent interaction ability with metals and ions as well as organic species. The current review reveals that GO has been used to produce a variety of functionalized nanocomposites, scaffolds, and advanced nanoparticle carriers. Accordingly, GO shows potential in a variety of research fields, such as tissue engineering, materials engineering, biomaterials, and drug delivery, indicating that the application of GO to biomedicine is particularly promising. More specifically, the recent application of GO in dentistry has provided outstanding results in antimicrobial action, regenerative dentistry, bone tissue engineering, drug delivery, physicomechanical property enhancement of dental biomaterials, and oral cancer treatment. The biocompatibilities of GO and its nanocomposites make them potential units in bone regeneration, osseointegration, and cell proliferation. Furthermore, its antibiofilm and antiadhesion properties have inspired researchers to develop GO for biofilm and caries prevention, as well as implant surface modification and as a quorum sensing inhibitor. This updated review is wide-ranging and provides a useful source for additional information on GO and its composites in dental research and applications.

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  • Tailoring the interaction between graphene oxide and antibacterial pyridinium salts by terminal functional groups Reviewed International journal

    R. Fujii, K. Okubo, S. Takashiba, A. Bianco, Y. Nishina

    Carbon   160   204 - 210   2020.4

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    Nanocarbons, especially two-dimensional carbons, have received considerable attention due to their unique structure and physical and chemical properties, which make them promising candidate materials for biomedical applications. In this study, we focus on graphene oxide (GO), which has many oxygenated functional groups and high affinity with water and biomaterials, and the synthesis of GO complexes with antibacterial agents, like cetylpyridinium chloride (CPC) and its derivatives. We found that the sustained release of CPCs from GO can be controlled by changing the terminal functional group of CPC. The prepared GO-CPC complexes were subjected to antibacterial tests against S. mutans. CPC with the carboxy group was degraded by the oxidizing property of GO, resulting in the loss of antibacterial properties. On the other hand, the other CPC derivatives were released from GO and showed antibacterial activities. Finally, we propose a new mechanism describing how GO and CPC form a functional complex, and how CPC is released from this complex. These findings will lead to pioneering the carbon-based functional antibacterial agents designed at the molecular level.

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  • Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial. Reviewed International journal

    Yohei Kamata, Takaomi Kessoku, Tomoko Shimizu, Takashi Kobayashi, Takeo Kurihashi, Satsuki Sato, Syotaro Kuraji, Norio Aoyama, Tomoyuki Iwasaki, Shogo Takashiba, Nobushiro Hamada, Toshiro Kodama, Toshiyuki Tamura, Satoshi Ino, Takuma Higurashi, Masataka Taguri, Takeharu Yamanaka, Masato Yoneda, Haruki Usuda, Koichiro Wada, Atsushi Nakajima, Masato Minabe

    Trials   21 ( 1 )   291 - 291   2020.3

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    BACKGROUND: We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD. METHODS: We will include adult patients (20-85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks. DISCUSSION: This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.

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  • Antimicrobial and antibiofilm effects of abietic acid on cariogenic Streptococcus mutans. Reviewed International journal

    Yuki Ito, Takashi Ito, Keisuke Yamashiro, Fumi Mineshiba, Kimito Hirai, Kazuhiro Omori, Tadashi Yamamoto, Shogo Takashiba

    Odontology   108 ( 1 )   57 - 65   2020.1

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    Dental caries is a type of oral microbiome dysbiosis and biofilm infection that affects oral and systemic conditions. For healthy life expectancy, natural bacteriostatic products are ideal for daily and lifetime use as anti-oral infection agents. This study aimed to evaluate the inhibitory effects of abietic acid, a diterpene derived from pine rosin, on the in vitro growth of cariogenic bacterial species, Streptococcus mutans. The effective minimum inhibitory concentration of abietic acid was determined through observation of S. mutans growth, acidification, and biofilm formation. The inhibitory effects of abietic acid on the bacterial membrane were investigated through the use of in situ viability analysis and scanning electron microscopic analysis. Cytotoxicity of abietic acid was also examined in the context of several human cell lines using tetrazolium reduction assay. Abietic acid was found to inhibit key bacterial growth hallmarks such as colony forming ability, adenosine triphosphate activity (both planktonic and biofilm), acid production, and biofilm formation. Abietic acid was identified as bacteriostatic, and this compound caused minimal damage to the bacterial membrane. This action was different from that of povidone-iodine or cetylpyridinium chloride. Additionally, abietic acid was significantly less cytotoxic compared to povidone-iodine, and it exerted lower toxicity towards epithelial cells and fibroblasts compared to that against monocytic cells. These data suggest that abietic acid may prove useful as an antibacterial and antibiofilm agent for controlling S. mutans infection.

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  • High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration. Reviewed International journal

    Keisuke Yamashiro, Hidetaka Ideguchi, Hiroaki Aoyagi, Chiaki Yoshihara-Hirata, Anna Hirai, Risa Suzuki-Kyoshima, Yao Zhang, Hidenori Wake, Masahiro Nishibori, Tadashi Yamamoto, Shogo Takashiba

    Frontiers in immunology   11   1461 - 1461   2020

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    High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein of about 30 kDa. It is released from a variety of cells into the extracellular milieu in response to inflammatory stimuli and acts on specific cell-surface receptors, such as receptors for advanced glycation end-products (RAGE), Toll-like receptor (TLR)2, TLR4, with or without forming a complex with other molecules. HMGB1 mediates various mechanisms such as inflammation, cell migration, proliferation, and differentiation. On the other hand, HMGB1 enhances chemotaxis acting through the C-X-C motif chemokine ligand (CXCL)12/C-X-C chemokine receptor (CXCR)4 axis and is involved in regeneration. In the oral cavity, high levels of HMGB1 have been detected in the gingival tissue from periodontitis and peri-implantitis patients, and it has been shown that secreted HMGB1 induces pro-inflammatory cytokine expression, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, which prolong inflammation. In contrast, wound healing after tooth extraction or titanium dental implant osseointegration requires an initial acute inflammation, which is regulated by secreted HMGB1. This indicates that secreted HMGB1 regulates angiogenesis and bone remodeling by osteoclast and osteoblast activation and promotes bone healing in oral tissue repair. Therefore, HMGB1 can prolong inflammation in the periodontal tissue and, conversely, can regenerate or repair damaged tissues in the oral cavity. In this review, we highlight the role of HMGB1 in the oral cavity by comparing its function and regulation with its function in other diseases. We also discuss the necessity for further studies in this field to provide more specific scientific evidence for dentistry.

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  • Acute Prevertebral Abscesses Caused by Bacterial-infected Traumatic Tooth Fractures. Reviewed International journal

    Kazuyuki Matsunaga, Makoto Takemaru, Keisuke Yamashiro, Chiaki Yoshihara-Hirata, Ken Inohara, Yutaka Shimoe, Akio Tanaka, Masaru Kuriyama, Shogo Takashiba

    Acta medica Okayama   73 ( 5 )   449 - 456   2019.10

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    We report a case of acute prevertebral abscess caused by traumatic tooth fractures in a 77-year-old Japanese man. After being transferred to our hospital the patient was initially diagnosed with a neck hematoma; however, blood culture showed Streptococcus parasanguinis, an oral bacterium, and an MRI examination suggested prevertebral abscesses. Tooth fractures, severe periodontitis, and peri-implantitis with Streptococcus parasanguinis were observed. Antibiotics were administered and fractured teeth were extracted. The patient's condition then gradually improved. We concluded that bacteremia caused by traumatic tooth fractures induced the acute prevertebral abscesses.

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  • Construction and characterization of a PGN_0297 mutant of Porphyromonas gingivalis: evidence of the contribution of PGN_0297 to gingipain activity. Reviewed International journal

    Ono S, Nakayama M, Tachibana M, Shahriar ASM, Heling W, Takashiba S, Ohara N

    Acta Medica Okayama   73 ( 4 )   315 - 323   2019.8

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    The periodontal pathogen Porphyromonas gingivalis shows colonial pigmentation on blood agar and produces gingipains (Kgp, RgpA, and RgpB), cysteine proteases involved in an organism's virulence and pigmentation. We showed previously that deletion of the PGN_0300 gene abolished the pigmentation activity and reduced the proteolytic activity of gingipains. The role of the PGN_0297 gene, which consists of an operon with the PGN_0300 gene, is unclear. Herein we examined the effect of PGN_0297 gene deletion on the pigmentation and proteolytic activities and transcriptional levels of gingipains. A PGN_0297 gene deletion mutant (ΔPGN_0297) did not exhibit the pigmentation. The proteolytic activity of the gingipains was decreased in the culture supernatant and on the cell surface of ΔPGN_0297. The mutant ΔPGN_0297 failed to attenuate Akt phosphorylation at Thr308 and Ser473, but both phosphorylations were attenuated in the wild-type and its complementation strain. The deletion of PGN_0297 gene did not substantially affect the transcriptional levels of the gingipain genes kgp, rgpA, and rgpB. Taken together, these results indicate that PGN_0297 is closely involved in the secretion and maturation of gingipains.

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  • Effectiveness and safety of low-concentrated ozonized water for the reduction of contamination in dental unit water lines. Reviewed International journal

    Keisuke Okubo, Takashi Ito, Yasuyoshi Shiota, Yusuke Kawata, Tadashi Yamamoto, Shogo Takashiba

    Heliyon   5 ( 8 )   e02306   2019.8

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    Contamination of dental unit waterlines (DUWL) with heterotrophic bacteria can cause problems in immune compromised patients (aged, tumor and organ transplantation-patients). We focused on the use of low-concentrated ozonized water (OZW) as the biofilm formation restraint system for DUWL. Here, we examined the effects of low-concentrated OZW on the growth of bacteria and related biofilm formation and harmfulness to dental unit components (DUCs) in vitro. Objectives: To evaluate the bactericidal effects of OZW on biofilms in DUWL and DUC in vitro. Methods: Low-concentrated OZW (0.4 mg/L) was generated using an OZS-PTDX generator. Heterotrophic bacterial biofilms in old DUWL tubes and Candia albicans solution (control microbe) were treated with OZW for 1 h with gentle agitation before static culturing for 96 h in Reasoner's 2A liquid media. The control solutions were 0.1% cetylpyridinium chloride (CPC), chlorinated tap water (TW), and phosphate-buffered saline (PBS). Adenosine triphosphate (ATP) amounts of the microbes were measured and the biofilms of these microbes were observed using scanning electron microscopy (SEM). Moreover, surfaces of DUC soaked in OZW and TW were observed by SEM. Results: The OZW reduced ATP levels in microbes to 50% compared to TW and PBS treatment, although CPC reduced it below detection limits. SEM observation revealed deformation of microbes cultured with OZW, whereas no changes were seen on DUC surfaces. Conclusions: Low-concentrated OZW is bactericidal against heterotrophic bacteria biofilms and it is not harmful to DUC, suggesting that it might be useful in preventing DUWL contamination.

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  • Multidisciplinary clinical approach by sharing oral examination information to treat a diabetes patient with dysgeusia. Reviewed International journal

    Kazuyuki Matsunaga, Yasuko Yoshida, Makoto Takemaru, Keisuke Yamashiro, Ikuko Monden, Ken Inohara, Saki Nakagawa, Eriko Maeda, Kanako Nakahama, Tatsuo Kohriyama, Shogo Takashiba

    Clinical case reports   7 ( 5 )   877 - 880   2019.5

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    Taste alteration is one of the complications of severe diabetes. It is important in diabetes treatment to assess taste alteration and perform dietary counseling, therapeutic exercise, and oral care. In this case, multidisciplinary clinical approach by medical staff was successful for a severely diabetic patient with dysgeusia.

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  • Molecular imaging assessment of periodontitis lesions in an experimental mouse model Reviewed International journal

    Hidetaka Ideguchi, Keisuke Yamashiro, Tadashi Yamamoto, Masayuki Shimoe, Shoichi Hongo, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hiroaki Aoyagi, Mari Kawamura, Shogo Takashiba

    Clinical Oral Investigations   23 ( 2 )   821 - 827   2019.2

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    Objective: We aimed to evaluate molecular imaging as a novel diagnostic tool for mice periodontitis model induced by ligature and Porphyromonas gingivalis (Pg) inoculation. Materials and methods: Twelve female mice were assigned to the following groups: no treatment as control group (n = 4)
    periodontitis group induced by ligature and Pg as Pg group (n = 4)
    and Pg group treated with glycyrrhizinic acid (GA) as Pg + GA group (n = 4). All mice were administered a myeloperoxidase (MPO) activity-specific luminescent probe and observed using a charge-coupled device camera on day 14. Image analysis on all mice was conducted using software to determine the signal intensity of inflammation. Additionally, histological and radiographic evaluation for periodontal inflammation and bone resorption at the site of periodontitis, and quantitative enzyme-linked immunosorbent assay (ELISA) were conducted on three mice for each group. Each experiment was performed three times. Results: Levels of serum IgG antibody against P. gingivalis were significantly higher in the Pg than in the Pg + GA group. Histological analyses indicated that the number of osteoclasts and neutrophils were significantly lower in the Pg + GA than in the Pg group. Micro-CT image analysis indicated no difference in bone resorption between the Pg and Pg + GA groups. The signal intensity of MPO activity was detected on the complete craniofacial image
    moreover, strong signal intensity was localized specifically at the periodontitis site in the ex vivo palate, with group-wise differences. Conclusions: Molecular imaging analysis based on MPO activity showed high sensitivity of detection of periodontal inflammation in mice. Clinical relevance: Molecular imaging analysis based on MPO activity has potential as a diagnostic tool for periodontitis.

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  • Induction of migration of periodontal ligament cells by selective regulation of integrin subunits. Reviewed International journal

    Mari Kawamura, Tadashi Yamamoto, Keisuke Yamashiro, Shinsuke Kochi, Chiaki Yoshihara-Hirata, Hidetaka Ideguchi, Hiroaki Aoyagi, Kazuhiro Omori, Shogo Takashiba

    Journal of cellular and molecular medicine   23 ( 2 )   1211 - 1223   2019.2

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    The recruitment of tissue-resident stem cells is important for wound regeneration. Periodontal ligament cells (PDL cells) are heterogeneous cell populations with stemness features that migrate into wound sites to regenerate periodontal fibres and neighbouring hard tissues. Cell migration is regulated by the local microenvironment, coordinated by growth factors and the extracellular matrix (ECM). Integrin-mediated cell adhesion to the ECM provides essential signals for migration. We hypothesized that PDL cell migration could be enhanced by selective expression of integrins. The migration of primary cultured PDL cells was induced by platelet-derived growth factor-BB (PDGF-BB). The effects of blocking specific integrins on migration and ECM adhesion were investigated based on the integrin expression profiles observed during migration. Up-regulation of integrins α3, α5, and fibronectin was identified at distinct localizations in migrating PDL cells. Treatment with anti-integrin α5 antibodies inhibited PDL cell migration. Treatment with anti-integrin α3, α3-blocking peptide, and α3 siRNA significantly enhanced cell migration, comparable to treatment with PDGF-BB. Furthermore, integrin α3 inhibition preferentially enhanced adhesion to fibronectin via integrin α5. These findings indicate that PDL cell migration is reciprocally regulated by integrin α3-mediated inhibition and α5-mediated promotion. Thus, targeting integrin expression is a possible therapeutic strategy for periodontal regeneration.

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  • Involvement of PM2.5-bound protein and metals in PM2.5-induced allergic airway inflammation in mice Reviewed

    Keiki Ogino, Kenjiro Nagaoka, Tatsuo Ito, Kei Takemoto, Tomoaki Okuda, Shoji F. Nakayama, Noriyoshi Ogino, Yuka Seki, Hiroki Hamada, Shogo Takashiba, Yoshihisa Fujikura

    Inhalation Toxicology   30 ( 13-14 )   498 - 508   2018.12

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    Background: The aim of this study was to investigate the protein and trace element components of PM2.5 and their contribution to the allergic airway inflammation in BALB/c mice. Methods: PM2.5, treated at high temperature and with a strong acid to hydrolyze any protein content and remove trace elements, was administered to BALB/c mice. Allergic airway inflammation was compared between the three groups (saline, pure PM2.5 and treated PM2.5) by evaluating airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cells, serum IgE, the mRNA of various cytokine (IL-4, IL-5, IL-13, eotaxin-1 and CXCL3), mucus protein mRNA (MUC5ac and MUC5b) and the filtration of inflammatory cells in the lung. Results: The treatment of PM2.5 with a strong acid at a high temperature attenuated AHR, eosinophil percentage in BALF, mRNA levels of IL-13 and CXCL3 and peribronchial inflammation. On the contrary, the percentage of neutrophils in BALF, mRNA expression of MIP2α, EGFR, Nrf2, and TLR4 and 4-OH-2-nonenal levels in the lung was increased. Moreover, the treatment of the PM2.5 reduced PM2.5-bound proteins as well as the percentages of the trace elements in PM2.5 in the order Zn > Cu > Pb > P > S > Mn > Fe > Ca > Ni, whereas the percentage of C, Si and Cl increased. Conclusions: PM2.5 collected by of the cyclone system induced allergic airway inflammation in mice. PM2.5-bound proteins and acid-soluble metals may be involved in the pathogenesis of PM2.5-induced allergic airway inflammation.

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  • Fungal metabolite (+)-terrein suppresses IL-6/sIL-6R-induced CSF1 secretion by inhibiting JAK1 phosphorylation in human gingival fibroblasts. Reviewed International journal

    Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba

    Heliyon   4 ( 11 )   e00979 - e00979   2018.11

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    Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL-6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL-6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

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  • Fungal metabolite (

    Satoshi Yamamoto, Kazuhiro Omori, Hiroki Mandai, Masaaki Nakayama, Saki Nakagawa, Hiroya Kobayashi, Tadashi Kunimine, Hiroshi Yoshimura, Kyosuke Sakaida, Hidefumi Sako, Soichiro Ibaragi, Tadashi Yamamoto, Hiroshi Maeda, Seiji Suga, Shogo Takashiba

    HELIYON   4 ( 11 )   2018.11

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    Control of bacterial infection-induced inflammatory responses is one of the effective therapeutic approaches of periodontal diseases. Natural products such as lipid mediators and metabolites from microorganisms have been used for decreasing inflammation. We previously reported that (+)-terrein inhibited activation of STAT3 and ERK1/2 in interleukin-6 (IL-6) signaling cascade, leading to prevent vascular endothelial growth factor (VEGF) secretion in human gingival fibroblasts (HGFs). However, little is still known about the role of (+)-terrein on inflammatory responses. In this study, we provided the possibility of novel action that (+)-terrein inhibits activation of Janus-activated kinase 1 (JAK1), which has a central function in IL-6 signaling cascade, and alters expression of mRNAs and proteins induced by IL-6/soluble IL-6 receptor (sIL6R) stimulation in HGFs. First, we performed PCR array to examine IL-6/sIL6R-induced mRNA expression, and then expression of mRNA and protein of colony stimulating factor-1 (CSF1) and VEGF were clearly determined by quantitative RT-PCR and ELISA, respectively. Treatment with (+)-terrein suppressed expression of mRNA and protein of CSF1 and VEGF by IL-6/sIL-6R stimulation. Next, to test the effect of (+)-terrein on IL-6/sIL-6R signaling cascade, we demonstrated whether (+)-terrein affects phosphorylation of JAK1 and its downstream proteins, Akt and SHP-2. Western blotting revealed that (+)-terrein inhibited IL-6/sIL-6R-induced phosphorylation of JAK1, Akt, and SHP-2. Therefore, (+)-terrein suppresses IL-6/sIL-6R-induced expression of CSF1 and VEGF via inhibition of JAK1, Akt, and SHP-2. Based on our results, we suggest that (+)-terrein is a candidate compound for anti-inflammatory effect associated with IL-6 signaling.

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  • HMGB1-induced inflammatory response promotes bone healing in murine tooth extraction socket Reviewed International journal

    Hiroaki Aoyagi, Keisuke Yamashiro, Chiaki Hirata-Yoshihara, Hidetaka Ideguchi, Mutsuyo Yamasaki, Mari Kawamura, Tadashi Yamamoto, Shinsuke Kochi, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

    Journal of Cellular Biochemistry   119 ( 7 )   5481 - 5490   2018.7

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    High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 has been suggested to mediate various inflammatory diseases. However, it is still unknown whether HMGB1 is involved in a healing process in the tooth extraction socket, the tissue containing gingival epithelium, and alveolar bone that is exposed to oral bacteria. In this study, we constructed a murine tooth extraction model with anti-HMGB1 neutralization antibody administration and observed the inflammatory response and bone healing process in tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity, histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells was inhibited by anti-HMGB1 antibody administration. The MPO activity around the tooth extraction socket was significantly reduced, and the numbers of CD31- and CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment samples than in the control samples. The TRAP-positive cells, osteocalcin positive cells, and the neoplastic bone area were significantly lower in anti-HMGB1 antibody treatment samples than in control samples. The expression levels of IL-1β and VEGF-A were also decreased in anti-HMGB1 antibody treatment samples compared to that in control samples. Secreted HMGB1 induced initial acute inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was associated with angiogenesis and bone remodeling by osteoclast and osteoblast activation and promoted bone healing in the tooth extraction socket.

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  • Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study Reviewed

    Chieko Kudo, Wee Soo Shin, Nobuhiro Sasaki, Kazuo Harai, Kai Kato, Hiroaki Seino, Eiji Goke, Takemasa Fujino, Nobuichi Kuribayashi, Youko Onuki Pearce, Masato Taira, Ryoji Matsushima, Masato Minabe, Shogo Takashiba, Kiyotaka Fujii, Tooru Hanai, Kouya Honda, Yoshichika Horiuchi, Hiroshi Inoue, Kiyoo Ishige, Shinichi Itoh, Sachiho Iwatsuka, Tomoko Kakugawa, Hideto Komai, Chikara Morimoto, Mitsutaka Motoyoshi, Masato Nakamura, Mikiko Niida, Ryuji Numaguchi, Kiyomi Oono, Hidetoshi Sakai, Yasunari Sakomura, Takaaki Shinohara, Yuichi Takakaze, Yukio Tsuruta, Daigaku Uchida, Norihide Ueno, Osamu Yasuda, Periodontitis and Atherosclerosis Project-Tokyo and Chiba Consortiums

    Odontology   106 ( 3 )   349 - 349   2018.7

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    Unfortunately, in Table-5 of the original article, the parameter in the 5th row was published incorrectly as “LDL-C (mg/dL)”. The correct parameter should read as “HDL-C (mg/dL)”.

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  • Effects of periodontal treatment on carotid intima-media thickness in patients with lifestyle-related diseases: Japanese prospective multicentre observational study Reviewed

    Chieko Kudo, Wee Soo Shin, Nobuhiro Sasaki, Kazuo Harai, Kai Kato, Hiroaki Seino, Eiji Goke, Takemasa Fujino, Nobuichi Kuribayashi, Youko Onuki Pearce, Masato Taira, Ryoji Matsushima, Masato Minabe, Shogo Takashiba, Kiyotaka Fujii, Tooru Hanai, Kouya Honda, Yoshichika Horiuchi, Hiroshi Inoue, Kiyoo Ishige, Shinichi Itoh, Sachiho Iwatsuka, Tomoko Kakugawa, Hideto Komai, Chikara Morimoto, Mitsutaka Motoyoshi, Masato Nakamura, Mikiko Niida, Ryuji Numaguchi, Kiyomi Oono, Hidetoshi Sakai, Yasunari Sakomura, Takaaki Shinohara, Yuichi Takakaze, Yukio Tsuruta, Daigaku Uchida, Norihide Ueno, Osamu Yasuda, Periodontitis and Atherosclerosis Project-Tokyo and Chiba Consortiums

    Odontology   106 ( 3 )   349 - 327   2018.7

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    Unfortunately, in Table-5 of the original article, the parameter in the 5th row was published incorrectly as “LDL-C (mg/dL)”. The correct parameter should read as “HDL-C (mg/dL)”.

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  • Anti-HMGB1 neutralizing antibody attenuates periodontal inflammation and bone resorption in a murine periodontitis model Reviewed International journal

    Chiaki Yoshihara-Hirata, Keisuke Yamashiro, Tadashi Yamamoto, Hiroaki Aoyagi, Hidetaka Ideguchi, Mari Kawamura, Risa Suzuki, Mitsuaki Ono, Hidenori Wake, Masahiro Nishibori, Shogo Takashiba

    Infection and Immunity   86 ( 5 )   2018.5

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    High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is secreted into the extracellular milieu in response to inflammatory stimuli. The secreted HMGB1 mediates various inflammatory diseases, including periodontitis
    however, the underlying mechanisms of HMGB1-induced periodontal inflammation are not completely understood. Here, we examined whether anti-HMGB1 neutralizing antibody inhibits periodontal progression and investigated the molecular pathology of HMGB1 in vitro and in vivo. In vitro analysis indicated that HMGB1, granulocytemacrophage colony-stimulating factor (GM-CSF), and interleukin-1β (IL-1β) were secreted in response to tumor necrosis factor-α (TNF-α) stimuli in human gingival epithelial cells (HGECs) and human monocytic leukemia cells (THP-1) treated with phorbol myristate acetate. Increased levels of GM-CSF and IL-1β were observed in the conditioned media from TNF-α-stimulated HGECs and THP-1 in vitro. Simultaneous stimulation with TNF-α and anti-HMGB1 antibody significantly decreased TNF-α- induced inflammatory cytokine secretion. Experimental periodontitis was induced in mice using Porphyromonas gingivalis-soaked ligatures. The extracellular translocation was confirmed in gingival epithelia in the periodontitis model mice by immunofluorescence analysis. Systemic administration of anti-HMGB1 neutralizing antibody significantly inhibited translocation of HMGB1. The anti-HMGB1 antibody inhibited periodontal inflammation, expression of IL-1β and C-X-C motif chemokine ligand 1 (CXCL1), migration of neutrophils, and bone resorption, shown by bioluminescence imaging of myeloperoxidase activity, quantitative reverse transcription-PCR (RT-PCR), and micro-computed tomography analysis. These findings indicate that HMGB1 is secreted in response to inflammatory stimuli caused by periodontal infection, which is crucial for the initiation of periodontitis, and the anti-HMGB1 antibody attenuates the secretion of a series of inflammatory cytokines, consequently suppressing the progression of periodontitis.

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  • Correction to: Expression of optineurin isolated from rat-injured dental pulp and the effects on inflammatory signals in normal rat kidney cells (Odontology, (2018), 106, 2, (135-144), 10.1007/s10266-017-0314-5) Reviewed

    Kyoko Senoo, Keisuke Yamashiro, Tadashi Yamamoto, Fumio Myokai, Mari Kawamura, Shogo Takashiba

    Odontology   106 ( 2 )   223 - 223   2018.4

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    In the original publication of the article, one of the author name was published incorrectly as “Keisuke Yamashairo” and correct name should be “Keisuke Yamashiro”.

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  • Expression of optineurin isolated from rat-injured dental pulp and the effects on inflammatory signals in normal rat kidney cells Reviewed International journal

    Senoo K, Yamashiro K, Yamamoto T, Myokai F, Kawamura M, Takashiba S

    Odontology   106 ( 2 )   135 - 144   2018.4

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    We previously isolated rat 14.7K-interacting protein-2 (rFIP-2) from the rat-wounded pulp. The protein, homologous to human FIP-2, is known as optineurin and was initially identified as a novel tumor necrosis factor-α (TNF-α)-inducible protein, and more recently, as an autophagy receptor. However, the biological role of optineurin in dental pulp remains elusive. We hypothesized that optineurin has a crucial role in regulating molecular processes during pulp inflammatory responses induced by TNF-α. We examined the kinetics of optineurin expression in pulp inflammation. Optineurin localization and expression were examined using rat pulp fibroblasts. The cells were treated with pharmacological inhibitors for TNF-α-induced inflammatory signals or with hydrogen peroxide as apoptotic stimuli. Stable optineurin-knockdown cells (OPTN-KD cells) were established by transfecting normal rat kidney cells with a vector expressing optineurin-specific small interfering RNA. Cell proliferation and the profiles of cytokines and intracellular signaling molecules were examined using OPTN-KD cells stimulated by TNF-α. Optineurin was localized in the cytoplasm and then translocated into the nucleus upon apoptotic stimuli. Optineurin expression was increased by TNF-α and decreased by a specific inhibitor of c-Jun N-terminal kinase. The OPTN-KD cells secreted smaller amounts of monocyte chemotactic protein-1 (MCP-1) and intracellular MCP-1 mRNA, and cell proliferation was significantly increased. Apoptosis-related signaling molecules were downregulated in OPTN-KD cells. These results demonstrated that optineurin is a crucial molecule mediated by TNF-α, which induces the production of inflammatory factors and apoptosis signaling, suggesting the presence of signaling interactions between optineurin and a transcription factor for MCP-1.

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  • Modulation of microenvironment for controlling the fate of periodontal ligament cells: the role of Rho/ROCK signaling and cytoskeletal dynamics Reviewed International journal

    Tadashi Yamamoto, Yuki Ugawa, Mari Kawamura, Keisuke Yamashiro, Shinsuke Kochi, Hidetaka Ideguchi, Shogo Takashiba

    Journal of Cell Communication and Signaling   12 ( 1 )   369 - 378   2018.3

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    Cells behave in a variety of ways when they perceive changes in their microenvironment
    the behavior of cells is guided by their coordinated interactions with growth factors, niche cells, and extracellular matrix (ECM). Modulation of the microenvironment affects the cell morphology and multiple gene expressions. Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) signaling is one of the key regulators of cytoskeletal dynamics and actively and/or passively determines the cell fate, such as proliferation, migration, differentiation, and apoptosis, by reciprocal communication with the microenvironment. During periodontal wound healing, it is important to recruit the residential stem cells into the defect site for regeneration and homeostasis of the periodontal tissue. Periodontal ligament (PDL) cells contain a heterogeneous fibroblast population, including mesenchymal stem cells, and contribute to the reconstruction of tooth-supporting tissues. Therefore, bio-regeneration of PDL cells has been the ultimate goal of periodontal therapy for decades. Recent stem cell researches have shed light on intrinsic ECM properties, providing paradigm shifts in cell fate determination. This review focuses on the role of ROCK activity and the effects of Y-27632, a specific inhibitor of ROCK, in the modulation of ECM-microenvironment. Further, it presents the current understanding of how Rho/ROCK signaling affects the fate determination of stem cells, especially PDL cells. In addition, we have also discussed in detail the underlying mechanisms behind the reciprocal response to the microenvironment.

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

    Kobayashi T, Kido JI, Ishihara Y, Omori K, Ito S, Matsuura T, Bando T, Wada J, Murasawa A, Nakazono K, Mitani A, Takashiba S, Nagata T, Yoshie H

    Journal of periodontology   89 ( 3 )   315 - 324   2018.3

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    BACKGROUND: A number of studies have suggested a bidirectional relationship of periodontitis with rheumatoid arthritis (RA) and type 2 diabetes mellitus (T2DM). However, the genetic factors that underlie these relationships have not been elucidated. METHODS: We conducted a multicenter case-control study that included 185 patients with RA and chronic periodontitis (CP), 149 patients with T2DM and CP, 251 patients with CP, and 130 systemically and periodontally healthy controls from a cohort of Japanese adults to assess the shared genetic risk factors for RA and CP as well as for T2DM and CP. A total of 17 candidate single nucleotide polymorphisms (SNPs) associated with RA, T2DM, and CP were genotyped. RESULTS: Multiple logistic regression analyses revealed that the KCNQ1 rs2237892 was significantly associated with comorbidity of RA and CP (P = 0.005) after adjustment for age, sex, and smoking status. The carriers of the T allele among patients with RA and CP showed significantly higher disease activity scores including 28 joints using C-reactive protein values than the non-carriers (P = 0.02), although the age, female percentage, and smoking status were comparable. Other SNPs were not associated with comorbidity of RA and CP, T2DM and CP, or susceptibility to CP. CONCLUSION: The results of the present pilot study suggest for the first time that the KCNQ1 rs2237892 may constitute a shared genetic risk factor for RA and CP, but not for T2DM and CP in Japanese adults.

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  • Effects of Mechanical Stress on Periodontal Ligament Reviewed

    Fujita Ayano, Morimatsu Masatoshi, Nishiyama Masayoshi, Takashiba Shogo, Naruse Keiji

    BIOPHYSICAL JOURNAL   114 ( 3 )   143A   2018.2

  • Effects of Lectins on initial attachment of cariogenic Streptococcus mutans Reviewed International journal

    Takashi Ito, Yasuhiro Yoshida, Yasuyoshi Shiota, Yuki Ito, Tadashi Yamamoto, Shogo Takashiba

    Glycoconjugate Journal   35 ( 1 )   41 - 51   2018.2

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    Oral bacteria initiate biofilm formation by attaching to tooth surfaces via an interaction of a lectin-like bacterial protein with carbohydrate chains on the pellicle. This study aimed to find naturally derived lectins that inhibit the initial attachment of a cariogenic bacterial species, Streptococcus mutans (S. mutans), to carbohydrate chains in saliva in vitro. Seventy kinds of lectins were screened for candidate motifs that inhibit the attachment of S. mutans ATCC 25175 to a saliva-coated culture plate. The inhibitory effect of the lectins on attachment of the S. mutans to the plates was quantified by crystal violet staining, and the biofilm was observed under a scanning electron microscope (SEM). Surface plasmon resonance (SPR) analysis was performed to examine the binding of S. mutans to carbohydrate chains and the binding of candidate lectins to carbohydrate chains, respectively. Moreover, binding assay between the biotinylated-lectins and the saliva components was conducted to measure the lectin binding. Lectins recognizing a salivary carbohydrate chain, Galβ1-3GalNAc, inhibited the binding of S. mutans to the plate. In particular, Agaricus bisporus agglutinin (ABA) markedly inhibited the binding. This inhibition was confirmed by SEM observation. SPR analysis indicated that S. mutans strongly binds to Galβ1-3GalNAc, and ABA binds to Galβ1-3GalNAc. Finally, the biotinylated Galβ1-3GalNAc-binding lectins including ABA demonstrated marked binding to the saliva components. These results suggest that ABA lectin inhibited the attachment of S. mutans to Galβ1-3GalNAc in saliva and ABA can be useful as a potent inhibitor for initial attachment of oral bacteria and biofilm formation.

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  • IS1598 (IsPg4) distributed to abscess-forming strains of Porphyromonas gingivalis may enhance virulence through upregulation of nrdD-like gene expression Reviewed International journal

    Norihiro Sonoi, Hiroshi Maeda, Toshimitsu Murauchi, Tadashi Yamamoto, Kazuhiro Omori, Susumu Kokeguchi, Koji Naruishi, Shogo Takashiba

    New Microbiologica   41 ( 1 )   52 - 60   2018.1

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    An insertion sequence, IS1598 (IsPg4) has been found in virulent strains of Porphyromonas gingivalis in a murine abscess model. The present study was performed to investigate the effects of genetic rearrangements by IS1598 on the phenotypic characteristics of the virulent strains. For this purpose, we searched for a common insertion site of IS1598 among the virulent strains. Through cloning and database search, a common insertion site was identified beside an nrdD-like gene in the virulent FDC 381, W83 and W50 strains. In this region, predicted promoters of the nrdD-like gene and IS1598 are located in tandem, and accumulation of nrdD-like gene mRNA was 5-fold higher in virulent strains (W83, W50, FDC 381) than avirulent strains (ATCC33277, SU63, SUNY1021, ESO59 without IS1598). The role of the nrdD-like gene in virulence of P. gingivalis was investigated by constructing a nrdD-deficient mutant. In the murine abscess model, the parental W83 strain produced necrotic abscesses, while the nrdD-deficient mutant had almost lost this ability. Insertion of IS1598 into the nrdD-like gene promoter region may be related to the phenotypic differences in virulence among P. gingivalis strains through upregulation of the expression of this gene.

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  • Regulatory mechanism of CCN2 production by serotonin (5-HT) via 5-HT2A and 5-HT2B receptors in chondrocytes Reviewed

    Ayaka Hori, Takashi Nishida, Shogo Takashiba, Satoshi Kubota, Masaharu Takigawa

    PLOS ONE   12 ( 11 )   e0188014 - e0188014   2017.11

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  • Medication-related osteonecrosis of the jaws caused lethal sepsis in an edentulous patient with multiple systemic factors Reviewed

    Keisuke Yamashiro, Aki Sato, Fumihiko Okazaki, Makoto Nakano, Koichi Sawaki, Yasuhisa Hirata, Eiki Yamachika, Seiji Iida, Shogo Takashiba

    Clinical Case Reports   5 ( 2 )   97 - 103   2017.2

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    DOI: 10.1002/ccr3.751

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  • Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study. Reviewed International journal

    E Kakuta, Y Nomura, T Morozumi, T Nakagawa, T Nakamura, K Noguchi, A Yoshimura, Y Hara, O Fujise, F Nishimura, T Kono, M Umeda, M Fukuda, T Noguchi, N Yoshinari, C Fukaya, S Sekino, Y Numabe, N Sugano, K Ito, H Kobayashi, Y Izumi, H Takai, Y Ogata, S Takano, M Minabe, A Makino-Oi, A Saito, Y Abe, S Sato, F Suzuki, K Takahashi, T Sugaya, M Kawanami, N Hanada, S Takashiba, H Yoshie

    BMC oral health   17 ( 1 )   46 - 46   2017.1

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    BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

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  • Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study Reviewed

    T. Morozumi, T. Nakagawa, Y. Nomura, T. Sugaya, M. Kawanami, F. Suzuki, K. Takahashi, Y. Abe, S. Sato, A. Makino-Oi, A. Saito, S. Takano, M. Minabe, Y. Nakayama, Y. Ogata, H. Kobayashi, Y. Izumi, N. Sugano, K. Ito, S. Sekino, Y. Numabe, C. Fukaya, N. Yoshinari, M. Fukuda, T. Noguchi, T. Kono, M. Umeda, O. Fujise, F. Nishimura, A. Yoshimura, Y. Hara, T. Nakamura, K. Noguchi, E. Kakuta, N. Hanada, S. Takashiba, H. Yoshie

    Journal of Periodontal Research   51 ( 6 )   768 - 778   2016.12

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  • Smad2 overexpression enhances adhesion of gingival epithelial cells Reviewed

    Shoichi Hongo, Tadashi Yamamoto, Keisuke Yamashiro, Masayuki Shimoe, Kazuya Tomikawa, Yuki Ugawa, Shinsuke Kochi, Hidetaka Ideguchi, Hiroshi Maeda, Shogo Takashiba

    Archives of Oral Biology   71   46 - 53   2016.11

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  • The potential of positron emission tomography/computerized tomography (PET/CT) scanning as a detector of high-risk patients with oral infection during preoperative staging Reviewed

    Keisuke Yamashiro, Makoto Nakano, Koichi Sawaki, Fumihiko Okazaki, Yasuhisa Hirata, Shogo Takashiba

    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology   122 ( 2 )   242 - 249   2016.8

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  • Effects of new over-the-counter periodontal ointment-containing applicator with single-tuft brush on cytokine levels in gingival crevicular fluid during supportive periodontal therapy phase: a randomized double-blind clinical trial. Reviewed International journal

    K Takeuchi-Hatanaka, T Yasuda, Koji Naruishi, K Katsuragi-Fuke, J Inubushi, H Ootsuki, H Maeda, S Takashiba

    Journal of Periodontal Research   Vol.51 ( No.3 )   321 - 331   2016.6

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    This OTC medication is biochemically effective for steady chronic periodontitis in the supportive periodontal therapy phase.

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  • Synthetic Terrein Inhibits Progression of Head and Neck Cancer by Suppressing Angiogenin Production Reviewed

    Shibata A, Ibaragi S, Mandai H, Tsumura T, Kishimoto K, Okui T, Hassan NM, Shimo T, Omori K, Hu GF, Takashiba S, Suga S, Sasaki A

    Anticancer Reserach   36 ( 5 )   2161 - 2168   2016.5

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  • Randomized Placebo‐Controlled and Controlled Non‐Inferiority Phase III Trials Comparing Trafermin, a Recombinant Human Fibroblast Growth Factor 2, and Enamel Matrix Derivative in Periodontal Regeneration in Intrabony Defects Reviewed

    Masahiro Kitamura, Motoki Akamatsu, Masamitsu Kawanami, Yasushi Furuichi, Takeo Fujii, Mari Mori, Kazushi Kunimatsu, Hidetoshi Shimauchi, Yorimasa Ogata, Matsuo Yamamoto, Taneaki Nakagawa, Shuichi Sato, Koichi Ito, Takefumi Ogasawara, Yuichi Izumi, Kazuhiro Gomi, Kazuhisa Yamazaki, Hiromasa Yoshie, Mitsuo Fukuda, Toshihide Noguchi, Shogo Takashiba, Hidemi Kurihara, Toshihiko Nagata, Takafumi Hamachi, Katsumasa Maeda, Makoto Yokota, Ryuji Sakagami, Yoshitaka Hara, Kazuyuki Noguchi, Toshi Furuuchi, Takashi Sasano, Enyu Imai, Masatoshi Ohmae, Hayuru Koizumi, Mitsuru Watanuki, Shinya Murakami

    Journal of Bone and Mineral Research   31 ( 4 )   806 - 814   2016.4

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  • Involvement of an Skp-Like Protein, PGN_0300, in the Type IX Secretion System of Porphyromonas gingivalis Reviewed

    Yuko Taguchi, Keiko Sato, Hideharu Yukitake, Tetsuyoshi Inoue, Masaaki Nakayama, Mariko Naito, Yoshio Kondo, Konami Kano, Tomonori Hoshino, Koji Nakayama, Shogo Takashiba, Naoya Ohara

    Infection and Immunity   84 ( 1 )   230 - 240   2016.1

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    <title>ABSTRACT</title>

    The oral Gram-negative anaerobic bacterium
    <named-content content-type="genus-species">Porphyromonas gingivalis</named-content>
    is an important pathogen involved in chronic periodontitis. Among its virulence factors, the major extracellular proteinases, Arg-gingipain and Lys-gingipain, are of interest given their abilities to degrade host proteins and process other virulence factors. Gingipains possess C-terminal domains (CTDs) and are translocated to the cell surface or into the extracellular milieu by the type IX secretion system (T9SS). Gingipains contribute to the colonial pigmentation of the bacterium on blood agar. In this study, Omp17, the PGN_0300 gene product, was found in the outer membrane fraction. A mutant lacking Omp17 did not show pigmentation on blood agar and showed reduced proteolytic activity of the gingipains. CTD-containing proteins were released from bacterial cells without cleavage of the CTDs in the
    <italic>omp17</italic>
    mutant. Although synthesis of the anionic polysaccharide (A-LPS) was not affected in the
    <italic>omp17</italic>
    mutant, the processing of and A-LPS modification of CTD-containing proteins was defective. PorU, a C-terminal signal peptidase that cleaves the CTDs of other CTD-containing proteins, was not detected in any membrane fraction of the
    <italic>omp17</italic>
    mutant, suggesting that the defective maturation of CTD-containing proteins by impairment of Omp17 is partly due to loss of function of PorU. In the mouse subcutaneous infection experiment, the
    <italic>omp17</italic>
    mutant was less virulent than the wild type. These results suggested that Omp17 is involved in
    <named-content content-type="genus-species">P. gingivalis</named-content>
    virulence.

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  • Analysis of the relationship between periodontal disease and atherosclerosis within a local clinical system: a cross-sectional observational pilot study.

    Chieko Kudo, Wee Soo Shin, Masato Minabe, Kazuo Harai, Kai Kato, Hiroaki Seino, Eiji Goke, Nobuhiro Sasaki, Takemasa Fujino, Nobuichi Kuribayashi, Youko Onuki Pearce, Masato Taira, Hiroshi Maeda, Shogo Takashiba

    Odontology   103 ( 3 )   314 - 21   2015.9

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    It has been revealed that atherosclerosis and periodontal disease may have a common mechanism of "chronic inflammation". Several reports have indicated that periodontal infection is related to atherosclerosis, but none have yet reported such an investigation through the cooperation of local clinics. This study was performed in local Japanese clinics to examine the relationship between periodontal disease and atherosclerosis under collaborative medical and dental care. A pilot multicenter cross-sectional study was conducted on 37 medical patients with lifestyle-related diseases under consultation in participating medical clinics, and 79 periodontal patients not undergoing medical treatment but who were seen by participating dental clinics. Systemic examination and periodontal examination were performed at baseline, and the relationships between periodontal and atherosclerosis-related clinical markers were analyzed. There was a positive correlation between LDL-C level and plasma IgG antibody titer to Porphyromonas gingivalis. According to the analysis under adjusted age, at a cut-off value of 5.04 for plasma IgG titer to Porphyromonas gingivalis, the IgG titer was significantly correlated with the level of low-density lipoprotein cholesterol (LDL-C). This study suggested that infection with periodontal bacteria (Porphyromonas gingivalis) is associated with the progression of atherosclerosis. Plasma IgG titer to Porphyromonas gingivalis may be useful as the clinical risk marker for atherosclerosis related to periodontal disease. Moreover, the application of the blood examination as a medical check may lead to the development of collaborative medical and dental care within the local medical clinical system for the purpose of preventing the lifestyle-related disease.

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  • Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes. International journal

    H Murata, T Hattori, H Maeda, S Takashiba, M Takigawa, J Kido, T Nagata

    Journal of periodontal research   50 ( 4 )   452 - 60   2015.8

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    BACKGROUND AND OBJECTIVE: Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. MATERIAL AND METHODS: To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. RESULTS: Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. CONCLUSION: We identified TDP-43 as one of the novel TNF-α factors and found that it bound to the LPS-responsive element in the TNF-α promoter to increase TNF-α expression.

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  • Cut-off values of Functional Independence Measure scores for discharge destination Reviewed

    Koji Naruishi, Akiko Kunita, Toshihiko Nagata, Shogo Takashiba, Seiji Adachi

    Geriatrics & Gerontology International   15 ( 5 )   670 - 671   2015.5

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  • With regard to our manuscripts on the commercial saliva substitute, Oralbalance®—its formula has been changed Reviewed

    Yuko Sugiura, Yoshihiko Soga, Ichiro Tanimoto, Susumu Kokeguchi, Sachiko Morishige-Nishide, Kotoe Itami-Kono, Kanayo Takahashi, Nobuharu Fujii, Fumihiko Ishimaru, Mitsune Tanimoto, Kokoro Yamabe, Soichiro Tsutani, Fusanori Nishimura, Shogo Takashiba

    Supportive Care in Cancer   22 ( 12 )   3121 - 3122   2014.12

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  • Predictors of improved functional outcome in elderly inpatients after rehabilitation: a&nbsp;retrospective study Reviewed

    Koji Naruishi, Akiko Kunita, Katsuyuki Kubo, Toshihiko Nagata, Shogo Takashiba, Seiji Adachi

    Clinical Interventions in Aging   2133 - 2133   2014.12

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  • Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report

    Chieko Kudo, Hiroshi Wakabayashi, Masayuki Shimoe, Hiroya Kobayashi, Takashi Ito, Toshinori Ohkawa, Arisa Isoshima‐Nakamura, Junji Mineshiba, Norie Yoshioka, Kumiko Nawachi, Hiroshi Maeda, Toshihiko Matsuo, Hirofumi Makino, Shogo Takashiba

    Clinical Case Reports   2 ( 6 )   274 - 280   2014.12

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  • Gingival overgrowth caused by vitamin C deficiency associated with metabolic syndrome and severe periodontal infection: a case report

    Kazuhiro Omori, Yoshihisa Hanayama, Koji Naruishi, Kentaro Akiyama, Hiroshi Maeda, Fumio Otsuka, Shogo Takashiba

    Clinical Case Reports   2 ( 6 )   286 - 295   2014.12

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  • Synthetic (+)-terrein suppresses interleukin-6/soluble interleukin-6 receptor induced-secretion of vascular endothelial growth factor in human gingival fibroblasts Reviewed

    Hiroki Mandai, Kazuhiro Omori, Daisuke Yamamoto, Toki Tsumura, Kyouta Murota, Satoshi Yamamoto, Koichi Mitsudo, Soichiro Ibaragi, Akira Sasaki, Hiroshi Maeda, Shogo Takashiba, Seiji Suga

    Bioorganic & Medicinal Chemistry   22 ( 19 )   5338 - 5344   2014.10

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  • Distribution of oral mucosal bacteria with mecA in patients undergoing hematopoietic cell transplantation Reviewed

    Takayuki Ebinuma, Yoshihiko Soga, Takamaro Sato, Kazuyuki Matsunaga, Chieko Kudo, Hiroshi Maeda, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    Supportive Care in Cancer   22 ( 6 )   1679 - 1683   2014.6

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  • Overexpression of Smad2 inhibits proliferation of gingival epithelial cells. Reviewed International journal

    M Shimoe, T Yamamoto, N Shiomi, K Tomikawa, S Hongo, K Yamashiro, T Yamaguchi, H Maeda, S Takashiba

    Journal of periodontal research   49 ( 3 )   290 - 8   2014.6

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    BACKGROUND AND OBJECTIVE: Spatiotemporal inhibition of apical migration and proliferation of gingival epithelium are significant factors involved in periodontal regeneration. Transforming growth factor β (TGF-β) is important in multiple aspects of wound healing, and Smad2, a downstream transcription factor of TGF-β, has an inhibitory effect on re-epithelialization during gingival wound healing. Therefore, we investigated the effects on migration and proliferation status, and intra/extracellular signaling regulated by Smad2 overexpression in gingival epithelial cells. MATERIAL AND METHODS: Gingival epithelial cells were isolated from the palatal gingival tissue of transgenic mice overexpressing Smad2 driven by the Keratin14 promoter. Smad2 expression was identified by western blotting and immunofluorescence analysis. Scratch assay and 5-bromo-2'-deoxyuridine staining were performed to assess cell migration and proliferation. To inactivate TGF-β type I receptor, the cultures were supplemented with SB431542. Secreted TGF-β was quantified by ELISA. Smad2 target gene expression was examined by real-time RT-PCR and in vivo immunofluorescence analysis of gingival junctional epithelium. RESULTS: Smad2-overexpressing cells were confirmed to have significant phosphorylated Smad2 in the nucleus. Scratch assay and 5-bromo-2'-deoxyuridine staining indicated that Smad2-overexpressing cells showed no significant differences in migration, but had reduced proliferation rates compared to wild-type controls. SB431542 significantly inhibited Smad2 phosphorylation, which coincided with restoration of the proliferation rate in Smad2-overexpressing cells. ELISA of TGF-β release did not show any differences between genotypes. The cell cycle inhibitors, p15 and p21, showed significant upregulation in Smad2-overexpressing cells compared to wild-type controls. Moreover, junctional epithelium of the transgenic mice showed increased expression of P-Smad2, p15 and p21. CONCLUSION: The signaling activation triggered by overexpression of Smad2 was dependent on TGF-β type I receptor, and the activated Smad2 increased p15 and p21 expression, responsible for inhibiting cell cycle entry, resulting in antiproliferative effects on gingival epithelial cells. Understanding of Smad2-induced signaling would be useful for possible clinical application to regulate gingival epithelial downgrowth.

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  • Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses Reviewed

    Ryoma Nakao, Shogo Takashiba, Saori Kosono, Minoru Yoshida, Haruo Watanabe, Makoto Ohnishi, Hidenobu Senpuku

    Microbes and Infection   16 ( 1 )   6 - 16   2014.1

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  • Serum antibody response to group II chaperonin fromMethanobrevibacter oralisand human chaperonin CCT Reviewed

    Kimito Hirai, Hiroshi Maeda, Kazuhiro Omori, Tadashi Yamamoto, Susumu Kokeguchi, Shogo Takashiba

    Pathogens and Disease   68 ( 1 )   12 - 19   2013.6

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  • Cytokine expression in human dermal fibroblasts stimulated with eosinophil cationic protein measured by protein array Reviewed

    Takamaro Sato, Yoshihiko Soga, Tomoko Yamaguchi, Michio Meguro, Hiroshi Maeda, Joji Tada, Takayuki Otani, Masaharu Seno, Shogo Takashiba

    Asian Pacific Journal of Allergy and Immunology   31 ( 4 )   2013.4

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    DOI: 10.12932/ap0287.31.4.2013

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  • Antibiotic sensitivity of bacteria on the oral mucosa after hematopoietic cell transplantation Reviewed

    Soga Yoshihiko, Maeda Yoshinobu, Tanimoto Mitsune, Ebinuma Takayuki, Maeda Hiroshi, Takashiba Shogo

    Supportive Care in Cancer   21 ( 2 )   367 - 368   2013.2

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    DOI: 10.1007/s00520-012-1602-9

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  • 次世代『歯周病の科学』の構築 Invited Reviewed

    高柴 正悟

    日本歯周病学会会誌   54 ( 3 )   237 - 237   2013

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  • Assessment of the Plasma/Serum IgG Test to Screen for Periodontitis Reviewed

    C. Kudo, K. Naruishi, H. Maeda, Y. Abiko, T. Hino, M. Iwata, C. Mitsuhashi, S. Murakami, T. Nagasawa, T. Nagata, S. Yoneda, Y. Nomura, T. Noguchi, Y. Numabe, Y. Ogata, T. Sato, H. Shimauchi, K. Yamazaki, A. Yoshimura, S. Takashiba

    Journal of Dental Research   91 ( 12 )   1190 - 1195   2012.12

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    Chronic periodontitis is a silent infectious disease prevalent worldwide and affects lifestyle-related diseases. Therefore, efficient screening of patients is essential for general health. This study was performed to evaluate prospectively the diagnostic utility of a blood IgG antibody titer test against periodontal pathogens. Oral examination was performed, and IgG titers against periodontal pathogens were measured by ELISA in 1,387 individuals. The cut-off value of the IgG titer was determined in receiver operating characteristic curve analysis, and changes in periodontal clinical parameters and IgG titers by periodontal treatment were evaluated. The relationships between IgG titers and severity of periodontitis were analyzed. The best cut-off value of IgG titer against Porphyromonas gingivalis for screening periodontitis was 1.682. Both clinical parameters and IgG titers decreased significantly under periodontal treatment. IgG titers of periodontitis patients were significantly higher than those of healthy controls, especially in those with sites of probing pocket depth over 4 mm. Multiplied cut-off values were useful to select patients with severe periodontitis. A blood IgG antibody titer test for Porphyromonas gingivalis is useful to screen hitherto chronic periodontitis patients (ClinicalTrials.gov number NCT01658475).

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  • Smad2 Decelerates Re-epithelialization during Gingival Wound Healing Reviewed

    K. Tomikawa, T. Yamamoto, N. Shiomi, M. Shimoe, S. Hongo, K. Yamashiro, T. Yamaguchi, H. Maeda, S. Takashiba

    Journal of Dental Research   91 ( 8 )   764 - 770   2012.8

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    During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-β is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-β, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter ( k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-β/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

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  • Relationship between Periodontitis-Related Antibody and Frequent Exacerbations in Chronic Obstructive Pulmonary Disease Reviewed

    Tamaki Takahashi, Shigeo Muro, Naoya Tanabe, Kunihiko Terada, Hirofumi Kiyokawa, Susumu Sato, Yuma Hoshino, Emiko Ogawa, Kazuko Uno, Koji Naruishi, Shogo Takashiba, Michiaki Mishima

    PLoS ONE   7 ( 7 )   e40570 - e40570   2012.7

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  • Histological and immunohistochemical features of gingival enlargement in a patient with AML Reviewed

    Norihiro Sonoi, Yoshihiko Soga, Hiroshi Maeda, Koichi Ichimura, Tadashi Yoshino, Kazutoshi Aoyama, Nobuharu Fujii, Yoshinobu Maeda, Mitsune Tanimoto, Richard Logan, Judith Raber-Durlacher, Shogo Takashiba

    Odontology   100 ( 2 )   254 - 257   2012.7

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    DOI: 10.1007/s10266-011-0051-0

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  • A Foreword Invited Reviewed

    TAKASHIBA Syogo

    JOURNAL OF THE JAPANESE ORGANISATION FOR RESEARCH OF PERIODONTOLOGY   54 ( 1 )   3 - 4   2012.3

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    DOI: 10.2329/perio.54.3

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  • Influence of resin coating materials on Porphyromonas gingivalis attachment Reviewed

    Ai KUMADA, Yoshizo MATSUKA, Atsushi MINE, Mitsuaki ONO, Junji UEHARA, Norihiro SONOI, Takashi ITO, Shogo TAKASHIBA, Takuo KUBOKI

    Dental Materials Journal   31 ( 1 )   86 - 91   2012

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  • Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a Mucosal Immune Response Reviewed

    Ryoma Nakao, Hideki Hasegawa, Kuniyasu Ochiai, Shogo Takashiba, Akira Ainai, Makoto Ohnishi, Haruo Watanabe, Hidenobu Senpuku

    PLoS ONE   6 ( 10 )   e26163 - e26163   2011.10

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  • Bacterial substitution of coagulase-negative staphylococci for streptococci on the oral mucosa after hematopoietic cell transplantation Reviewed

    Soga Yoshihiko, Maeda Yoshinobu, Ishimaru Fumihiko, Tanimoto Mitsune, Maeda Hiroshi, Nishimura Fusanori, Takashiba Shogo

    Supportive Care in Cancer   19 ( 7 )   995 - 1000   2011.7

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    DOI: 10.1007/s00520-010-0923-9

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  • Chronic periodontitis with multiple risk factor syndrome: a case report. Reviewed International journal

    Shimoe M, Yamamoto T, Iwamoto Y, Shiomi N, Maeda H, Nishimura F, Takashiba S

    Journal of the International Academy of Periodontology   13 ( 2 )   40 - 47   2011.7

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    OBJECTIVE: Multiple risk factor syndrome is a clustering of cardiovascular risk factors, such as diabetes, dyslipidemia, hypertension, and obesity associated epidemiologically with insulin resistance. This report describes the clinical course of a patient suffering from severe periodontitis with multiple risk factor syndrome, and discusses the association between periodontal infection and systemic health. METHODS: The patient had a history of type 2 diabetes, dyslipidemia, and hypertension for over 10 years. At baseline, her hemoglobin A1 c was 8.1%. However, she had no diabetic complications except periodontitis. The IgG antibody titers against Porphyromonas gingivalis FDC 381 and SU63 were elevated above the mean of healthy subjects +2 standard deviations. Intensive periodontal treatment, including periodontal surgery, was performed to reduce periodontal infection and bacteremia. Her systemic and periodontal conditions were evaluated longitudinally for 10 years. RESULTS: Following periodontal treatment, antibody titers against Porphyromonas gingivalis and hemoglobin A1c values were significantly improved. The other clinical data and medication for her systemic condition also remained stable during supportive periodontal therapy. However, she developed myocardial infarction, and showed continuous deterioration of hemoglobin A1 c level and periodontitis. CONCLUSION: The long-term clustering of risk factors, such as diabetes, dyslipidemia, hypertension, and periodontitis, are associated with the development of myocardial infarction. Treatment of systemic conditions in combination with comprehensive periodontal treatment is important in management of patients with multiple risk factor syndrome.

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  • Specific In Situ Visualization of Plasma Cells Producing Antibodies against Porphyromonas gingivalis in Gingival Radicular Cyst Reviewed

    Shinya Tsuge, Yasuyoshi Mizutani, Kazuhiro Matsuoka, Tatsuya Sawasaki, Yaeta Endo, Koji Naruishi, Hiroshi Maeda, Shogo Takashiba, Kazuya Shiogama, Ken-ichi Inada, Yutaka Tsutsumi

    Journal of Histochemistry & Cytochemistry   59 ( 7 )   673 - 689   2011.7

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    The enzyme-labeled antigen method was applied to visualize plasma cells producing antibodies to Porphyromonas gingivalis, flora of the human oral cavity. Antibodies to P. gingivalis have reportedly been detected in sera of patients with periodontitis. Biotinylated bacterial antigens, Ag53, and four gingipain domains (Arg-pro, Arg-hgp, Lys-pro, and Lys-hgp) were prepared by the cell-free protein synthesis system using the wheat germ extract. In paraformaldehyde-fixed frozen sections of rat lymph nodes experimentally immunized with Ag53-positive and Ag53-negative P. gingivalis, plasma cells were labeled with biotinylated Arg-hgp and Lys-hgp. Antibodies to Ag53 were detected only in the nodes immunized with Ag53-positive bacteria. In two of eight lesions of gingival radicular cyst with inflammatory infiltration, CD138-positive plasma cells in frozen sections were signalized for Arg-hgp and Lys-hgp. An absorption study using unlabeled antigens confirmed the specificity of staining. The AlphaScreen method identified the same-type antibodies in tissue extracts but not in sera. Antibodies to Ag53, Arg-pro, and Lys-pro were undetectable. In two cases, serum antibodies to Arg-hgp and Lys-hgp were AlphaScreen positive, whereas plasma cells were scarcely observed within the lesions. These findings indicate the validity of the enzyme-labeled antigen method. This is the very first application of this novel histochemical technique to human clinical samples.

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  • Discovery of a patient with strongly suspected bullous pemphigoid in a ward by oral health care providers Reviewed

    N Kanda, Y Soga, M Meguro, A Tanabe, Y Yagi, Y Himuro, Y Fujiwara, S Takashiba, N Kobayashi

    International Journal of Dental Hygiene   9 ( 2 )   159 - 162   2011.5

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  • IMMUNE RESPONSES TO PORPHYROMONAS GINGIVALIS INFECTION SUPPRESS SYSTEMIC INFLAMMATORY RESPONSE IN EXPERIMENTAL MURINE MODEL Reviewed

    K. Naruishi, K. Omori, H. Maeda, N. Sonoi, K. Funakoshi, K. Hirai, M. Ishii, K. Kubo, H. Kobayashi, T. Tomiyama, D. Yamamoto, I. Tanimoto, K. Kunimatsu, S. Takashiba

    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS   25 ( 2 )   195 - 202   2011.4

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    Periodontitis is localized infectious disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (T: gingivalis), and the severity correlates to significance of immune responses. Recently, it has been reported that periodontitis is associated with the development of systemic disease such as diabetes and atherosclerosis because of increasing invasion of oral pathogens to the circulation. However, the association between local and systemic infectious responses is still unclear. In the present study, we examined the differences of biological responses in animals with or without bacterial infection. After Balb/c mice were infected subcutaneously with live P gingivalis W83, serum, skin and liver were collected according to experimental protocol. The skin and liver tissues were observed pathologically by haematoxylin-eosin staining, and serum IL-6 levels were measured using ELISA method. Throughout the experimental period, conditions of the mice were observed continuously. As expected, severe infiltration of leukocytes were observed at inflamed skin corresponding to the number of bacterial challenges. Although no inflammatory appearance of skin was observed, serum IL-6 levels were increased dramatically (P &lt; 0.01, Student&apos;s t-test) and liver tissues were injured in the mice without bacterial challenge. Interestingly, although severe inflammatory appearance of the skin was observed, serum IL-6 levels were not increased and no inflammatory responses were observed in the liver of the 3-times bacterially challenged group. Importantly, immunoglobulin G against P gingivalis W83 was detected in the blood of mice with 3-times bacterial challenge corresponding to improvement of weight loss and survival. In conclusion, although multiple infections develop severe localized inflammation, the immune system should be sufficient to protect the systemic inflammatory responses.

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  • Progress of oral care and reduction of oral mucositis-a pilot study in a hematopoietic stem cell transplantation ward Reviewed

    Soga Yoshihiko, Sugiura Yuko, Takahashi Kanayo, Nishimoto Hitomi, Maeda Yoshinobu, Tanimoto Mitsune, Takashiba Shogo

    Supportive Care in Cancer   19 ( 2 )   303 - 307   2011.2

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  • FGF-2 Stimulates Periodontal Regeneration: results of a multi-center randomized clinical trial Reviewed

    M. Kitamura, M. Akamatsu, M. Machigashira, Y. Hara, R. Sakagami, T. Hirofuji, T. Hamachi, K. Maeda, M. Yokota, J. Kido, T. Nagata, H. Kurihara, S. Takashiba, T. Sibutani, M. Fukuda, T. Noguchi, K. Yamazaki, H. Yoshie, K. Ioroi, T. Arai, T. Nakagawa, K. Ito, S. Oda, Y. Izumi, Y. Ogata, S. Yamada, H. Shimauchi, K. Kunimatsu, M. Kawanami, T. Fujii, Y. Furuichi, T. Furuuchi, T. Sasano, E. Imai, M. Omae, S. Yamada, M. Watanuki, S. Murakami

    Journal of Dental Research   90 ( 1 )   35 - 40   2011.1

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    The efficacy of the local application of recombinant human fibroblast growth factor-2 (FGF-2) in periodontal regeneration has been investigated. In this study, a randomized, double-blind, placebo-controlled clinical trial was conducted in 253 adult patients with periodontitis. Modified Widman periodontal surgery was performed, during which 200 µL of the investigational formulation containing 0% (vehicle alone), 0.2%, 0.3%, or 0.4% FGF-2 was administered to 2- or 3-walled vertical bone defects. Each dose of FGF-2 showed significant superiority over vehicle alone (p &lt; 0.01) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the 0.3% FGF-2 group. No significant differences among groups were observed in clinical attachment regained, scoring approximately 2 mm. No clinical safety problems, including an abnormal increase in alveolar bone or ankylosis, were identified. These results strongly suggest that topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.

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  • Prognosis of periodontitis recurrence after intensive periodontal treatment using examination of serum IgG antibody titer against periodontal bacteria Reviewed

    Noriko Sugi, Koji Naruishi, Chieko Kudo, Aya Hisaeda-Kako, Takayuki Kono, Hiroshi Maeda, Shogo Takashiba

    Journal of Clinical Laboratory Analysis   25 ( 1 )   25 - 32   2011

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  • Clinical and Immunological Assessment of Periodontal Disease in Japanese Leprosy Patients Reviewed

    Hideki Ohyama, Hiroshi Hongyo, Naoko Shimizu, Yoshikazu Shimizu, Fusanori Nishimura, Masatsugu Nakagawa, Hideo Arai, Nahoko Kato-Kogoe, Nobuyuki Terada, Atsushi Nagai, Shogo Takashiba, Hidemi Kurihara, Yoshio Nomura, Yoji Murayama

    JAPANESE JOURNAL OF INFECTIOUS DISEASES   63 ( 6 )   427 - 432   2010.11

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    Periodontitis is a chronic inflammatory disease caused by the infection of periodontopathic bacteria in dental plaque However, an individual's susceptibility to this disease appears to be associated with multiple genetic factors, as seen in the case of leprosy In order to gain a better understanding of the pathophysiology of periodontal disease in subjects with leprosy, we investigated the clinical features of periodontitis and the immunological responses against periodontopathic bacteria in 382 subjects with a history of leprosy and 451 age-matched control subjects The prevalence of periodontitis and the degree of periodontal pocket depth were found to be significantly higher in leprosy patients than in age-matched controls Furthermore, a comparison of the clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients showed that the probing pocket depth of L-lep patients with periodontal disease was significantly higher than that for T-lep patients In contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients were significantly lower than in T-lep patients These results imply that L-lep patients show more severe periodontal disease than T-lep patients or age-matched control subjects, and that low humoral immunity against P gingivalis might be one of the genetic factors determining periodontal disease susceptibility in leprosy patients

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  • The inhibition of DNA synthesis by prostaglandin E2 in human gingival fibroblasts is independent of the cyclic AMP-protein kinase A signal transduction pathway Reviewed

    H. Arai, Y. Nomura, M. Kinoshita, F. Nishimura, M. Takigawa, K. Takahashi, N. Washio, S. Takashiba, Y. Murayama

    Journal of Periodontal Research   33 ( 1 )   33 - 39   2010.6

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  • Antigenic group II chaperonin inMethanobrevibacter oralismay cross-react with human chaperonin CCT Reviewed

    K. Yamabe, H. Maeda, S. Kokeguchi, Y. Soga, M. Meguro, K. Naruishi, S. Asakawa, S. Takashiba

    Molecular Oral Microbiology   25 ( 2 )   112 - 122   2010.4

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  • Rapid detection ofmecAandspaby the loop-mediated isothermal amplification (LAMP) method Reviewed International journal

    Y. Koide, H. Maeda, K. Yamabe, K. Naruishi, T. Yamamoto, S. Kokeguchi, S. Takashiba

    Letters in Applied Microbiology   50 ( 4 )   386 - 392   2010.4

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    Aim:
    To develop a detection assay for staphylococcal mecA and spa by using loop-mediated isothermal amplification (LAMP) method.
    Methods and Results:
    Staphylococcus aureus and other related species were subjected to the detection of mecA and spa by both PCR and LAMP methods. The LAMP successfully amplified the genes under isothermal conditions at 64 degrees C within 60 min, and demonstrated identical results with the conventional PCR methods. The detection limits of the LAMP for mecA and spa, by gel electrophoresis, were 102 and 10 cells per tube, respectively. The naked-eye inspections were possible with 103 and 10 cells for detection of mecA and spa, respectively. The LAMP method was then applied to sputum and dental plaque samples. The LAMP and PCR demonstrated identical results for the plaque samples, although frequency in detection of mecA and spa by the LAMP was relatively lower for the sputum samples when compared to the PCR methods.
    Conclusion:
    Application of the LAMP enabled a rapid detection assay for mecA and spa. The assay may be applicable to clinical plaque samples.
    Significance and Impact of the Study:
    The LAMP offers an alternative detection assay for mecA and spa with a great advantage of the rapidity.

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  • Highly expressed genes in a rough-colony-forming phenotype ofAggregatibacter actinomycetemcomitans: implication of amip-like gene for the invasion of host tissue Reviewed

    Takemasa Maeda, Hiroshi Maeda, Kokoro Yamabe, Junji Mineshiba, Ichiro Tanimoto, Tadashi Yamamoto, Koji Naruishi, Susumu Kokeguchi, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   58 ( 2 )   226 - 236   2010.3

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  • Total bacterial counts on oral mucosa after using a commercial saliva substitute in patients undergoing hematopoietic cell transplantation Reviewed

    Sugiura Yuko, Soga Yoshihiko, Yamabe Kokoro, Tsutani Soichiro, Tanimoto Ichiro, Maeda Hiroshi, Kokeguchi Susumu, Fujii Nobuharu, Ishimaru Fumihiko, Tanimoto Mitsune, Nishimura Fusanori, Takashiba Shogo

    Supportive Care in Cancer   18 ( 3 )   395 - 398   2010.3

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  • Oral mucositis in patients receiving reduced-intensity regimens for allogeneic hematopoietic cell transplantation: comparison with conventional regimen Reviewed

    Kanayo Takahashi, Yoshihiko Soga, Yumeno Murayama, Mika Udagawa, Hitomi Nishimoto, Yuko Sugiura, Yoshinobu Maeda, Mitsune Tanimoto, Shogo Takashiba

    Supportive Care in Cancer   18 ( 1 )   115 - 119   2010.1

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  • Genetic Risk Factors for Periodontitis in a Japanese Population Reviewed

    KOBAYASHI T., NAGATA T., MURAKAMI S., TAKASHIBA S., KURIHARA H., IZUMI Y., NUMABE Y., WATANABE H., KATAOKA M., NAGAI A., HAYASHI J., OHYAMA H., OKAMATSU Y., INAGAKI Y., TAI H., YOSHIE H.

    88 ( 12 )   1137 - 1141   2009.12

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

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  • Porphyromonas gingivalisfimbriae-dependent interleukin-6 autocrine regulation by increase of gp130 in endothelial cells Reviewed

    Y-S. Ho, M-T. Lai, S-J. Liu, C-T. Lin, K. Naruishi, S. Takashiba, H-H. Chou

    Journal of Periodontal Research   44 ( 4 )   550 - 556   2009.8

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  • Febrile neutropenia and periodontitis: lessons from a case periodontal treatment in the intervals between chemotherapy cycles for leukemia reduced febrile neutropenia Reviewed

    Soga Yoshihiko, Yamasuji Yoshiko, Kudo Chieko, Matsuura-Yoshimoto Kaori, Yamabe Kokoro, Sugiura Yuko, Maeda Yoshinobu, Ishimaru Fumihiko, Tanimoto Mitsune, Nishimura Fusanori, Takashiba Shogo

    Supportive Care in Cancer   17 ( 5 )   581 - 587   2009.5

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  • Antibacterial effect of bactericide immobilized in resin matrix Reviewed

    Naoko Namba, Yasuhiro Yoshida, Noriyuki Nagaoka, Seisuke Takashima, Kaori Matsuura-Yoshimoto, Hiroshi Maeda, Bart Van Meerbeek, Kazuomi Suzuki, Shogo Takashiba

    Dental Materials   25 ( 4 )   424 - 430   2009.4

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    DOI: 10.1016/j.dental.2008.08.012

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

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

    Journal of Periodontology   80 ( 4 )   663 - 671   2009.4

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  • Human leukocyte histocompatibility antigen class II-induced cytokines from human gingival fibroblasts promote proliferation of human umbilical vein endothelial cells: potential association with enhanced angiogenesis in chronic periodontal inflammation Reviewed

    Y. Okada, M. Meguro, H. Ohyama, S. Yoshizawa, K. Takeuchi-Hatanaka, N. Kato, S. Matsushita, S. Takashiba, F. Nishimura

    Journal of Periodontal Research   44 ( 1 )   103 - 109   2009.2

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  • IL-6/sIL-6R enhances cathepsin B and L production via caveolin-1-mediated JNK-AP-1 pathway in human gingival fibroblasts Reviewed

    Tomoko Yamaguchi, Koji Naruishi, Hideo Arai, Fusanori Nishimura, Shogo Takashiba

    Journal of Cellular Physiology   217 ( 2 )   423 - 432   2008.11

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  • Evaluation of xerostomia in hematopoietic cell transplantation by a simple capacitance method device Reviewed

    Sugiura Yuko, Soga Yoshihiko, Nishide Sachiko, Kono Kotoe, Takahashi Kanayo, Fujii Nobuharu, Ishimaru Fumihiko, Tanimoto Mitsune, Nishimura Fusanori, Takashiba Shogo

    Supportive Care in Cancer   16 ( 10 )   1197 - 1200   2008.10

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    DOI: 10.1007/s00520-008-0470-9

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  • Distribution ofArchaeain Japanese patients with periodontitis and humoral immune response to the components Reviewed

    Kokoro Yamabe, Hiroshi Maeda, Susumu Kokeguchi, Ichiro Tanimoto, Norihiro Sonoi, Susumu Asakawa, Shogo Takashiba

    FEMS Microbiology Letters   287 ( 1 )   69 - 75   2008.10

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    DOI: 10.1111/j.1574-6968.2008.01304.x

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  • Rapid and simple detection of eight major periodontal pathogens by the loop-mediated isothermal amplification method Reviewed

    Junko Miyagawa, Hiroshi Maeda, Toshimitsu Murauchi, Susumu Kokeguchi, Kokoro Yamabe, Ichiro Tanimoto, Fusanori Nishimura, Kazuhiro Fukui, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   53 ( 3 )   314 - 321   2008.8

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  • Periodontal Tissue Regeneration Using Fibroblast Growth Factor -2: Randomized Controlled Phase II Clinical Trial Reviewed

    Masahiro Kitamura, Keisuke Nakashima, Yusuke Kowashi, Takeo Fujii, Hidetoshi Shimauchi, Takashi Sasano, Toshi Furuuchi, Mitsuo Fukuda, Toshihide Noguchi, Toshiaki Shibutani, Yukio Iwayama, Shogo Takashiba, Hidemi Kurihara, Masami Ninomiya, Jun-ichi Kido, Toshihiko Nagata, Takafumi Hamachi, Katsumasa Maeda, Yoshitaka Hara, Yuichi Izumi, Takao Hirofuji, Enyu Imai, Masatoshi Omae, Mitsuru Watanuki, Shinya Murakami

    PLoS ONE   3 ( 7 )   e2611 - e2611   2008.7

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  • Chemotactic response of periodontal ligament cells decreases with donor age: association with reduced expression of c-fos Reviewed

    Y. Asahara, F. Nishimura, H. Arai, H. Kurihara, S. Takashiba, Y. Murayama

    Oral Diseases   5 ( 4 )   337 - 343   2008.6

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  • Antimicrobial effects of the saliva substitute, Oralbalance®, against microorganisms from oral mucosa in the hematopoietic cell transplantation period Reviewed

    Yuko Sugiura, Yoshihiko Soga, Ichiro Tanimoto, Susumu Kokeguchi, Sachiko Nishide, Kotoe Kono, Kanayo Takahashi, Nobuharu Fujii, Fumihiko Ishimaru, Mitsune Tanimoto, Kokoro Yamabe, Soichiro Tsutani, Fusanori Nishimura, Shogo Takashiba

    Supportive Care in Cancer   16 ( 4 )   421 - 424   2008.4

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  • Polymorphisms in the 5' flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population Reviewed

    Kazu Takeuchi-Hatanaka, Hideki Ohyama, Fusanori Nishimura, Nahoko Kato-Kogoe, Yoshihiko Soga, Sho Matsushita, Keiji Nakasho, Koji Yamanegi, Naoko Yamada, Nobuyuki Terada, Shogo Takashiba

    Journal of Clinical Periodontology   35 ( 4 )   317 - 323   2008.4

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    DOI: 10.1111/j.1600-051x.2008.01208.x

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  • Appearance of Multidrug-Resistant Opportunistic Bacteria on the Gingiva During Leukemia Treatment Reviewed

    Yoshihiko Soga, Takashi Saito, Fusanori Nishimura, Fumihiko Ishimaru, Junji Mineshiba, Fumi Mineshiba, Hirokazu Takaya, Hideaki Sato, Chieko Kudo, Susumu Kokeguchi, Nobuharu Fujii, Mitsune Tanimoto, Shogo Takashiba

    Journal of Periodontology   79 ( 1 )   181 - 186   2008.1

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  • Evaluation of Immunoglobulin G Antibody Titer Measurement in the Simplified Test for Multiple Bacterial Infection in Periodontal Disease Based on Self-Sampling of Fingertip Capillary Blood:-Focusing on Porphyromonas gingivalis Antigen- Reviewed

    Maehata Eisuke, Maehata Yojiro, Lee Masaichi-Cong-il, Kudo Chieko, Takashiba Shogo, Shimomura Hiroji, Yamakado Minoru, Yano Masao, Shiba Teruo, Hatakeyama Ikuo, Inoue Minoru, Kouka Kunio, Adachi Tetsuo, Kishikawa Naoya, Kuroda Naotaka, Sugimoto Shinya, Watanabe Hiromi, Koga Kazumasa, Ikoshi Naoko, Shimizu Katsuhisa

    Official Journal of the Japanese Society of Human Dry Dock   22 ( 6 )   35 - 41   2008

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    Background Periodontal disease is a multiple infection caused by bacteria represented by Porphyromonas gingivalis (Pg). The prevalence of periodontal disease is high, as it predominantly affects the people in the same age range as diabetes mellitus, but it is often overlooked because of the lack of subjective symptoms. There has been a need for the introduction of self-sampled device-treated plasma using fingertip capillary blood in routine tests.<br>Methods Based on the report by Kudo et al. (Beppu Conference 2006, p.46, 2006) on enzyme-linked immunosorbent assay (ELISA) as a blood test for periodontal disease bacteria, the precision and disease specificity were examined towards the establishment of a methodology for routine tests.<br>Results The intra-assay reproducibility of the measurements using Pg and 3 other types of antigens, Prevotella intermedia (Pi), Eikenella corroders (Ec), and Actinobacillus actinomycetemcomitans (Aa), was coefficient of variation (CV) 4-7%, and the results from capillary blood and those from venous blood were closely analogous to each other with a correlation (r) of 0.900 or more. The difference between the non-periodontal control subjects group and the periodontal disease group in the distribution of data on histograms using the Pg antigen was approximately 7-fold. In addition, the correlation with mean periodontal pocket depth was significant (r=0.597, p<0.001) in the group showing the test results (SD index; SDI) of 20 or more. These results substantiated the specificity of this method.<br>Conclusion The ability to detect periodontal disease in the setting of "Human Dry Dock" screening examinations using the sampling and test methods proposed by us would be an important means to improve services. This study established the practical feasibility of this approach.

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  • Focal adhesion kinase mediates human leukocyte histocompatibility antigen class II-induced signaling in gingival fibroblasts

    S. Yoshizawa, M. Meguro, H. Ohyama, K. Takeuchi-Hatanaka, S. Matsushita, S. Takashiba, F. Nishimura

    Journal of Periodontal Research   42 ( 6 )   572 - 579   2007.12

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  • Macrophage-Adipocyte Interaction: Marked Interleukin-6 Production by Lipopolysaccharide** Reviewed

    Akiko Yamashita, Yoshihiko Soga, Yoshihiro Iwamoto, Sayuri Yoshizawa, Hirotaka Iwata, Susumu Kokeguchi, Shogo Takashiba, Fusanori Nishimura

    Obesity   15 ( 11 )   2549 - 2552   2007.11

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  • cAMP-response element binding protein (CREB) regulates cyclosporine-A-mediated down-regulation of cathepsin B and L synthesis Reviewed

    Kazuhiro Omori, Koji Naruishi, Tomoko Yamaguchi, Shun-Ai Li, Mayumi Yamaguchi-Morimoto, Kaori Matsuura, Hideo Arai, Kohji Takei, Shogo Takashiba

    Cell and Tissue Research   330 ( 1 )   75 - 82   2007.9

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  • High glucose up-regulates lipopolysaccharide-stimulated inflammatory cytokine production via c-jun N-terminal kinase in the monocytic cell line THP-1 Reviewed

    Hirotaka Iwata, Yoshihiko Soga, Michio Meguro, Sayuri Yoshizawa, Yuka Okada, Yoshihiro Iwamoto, Akiko Yamashita, Shogo Takashiba, Fusanori Nishimura

    Journal of Endotoxin Research   13 ( 4 )   227 - 234   2007.8

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    Diabetic subjects are susceptible to atherosclerosis. It has been postulated that inflammation plays a crucial role in atherogenesis. Since previous studies suggested persistent low-grade infection by Gram-negative bacteria such as Chlamydia spp. and/or periodontal infection is associated with increased atherogenesis among diabetic subjects, we hypothesized that macrophages under hyperglycemia respond to lipopolysaccharide (LPS) challenge in a more exaggerated manner than under normal glucose conditions. Therefore, we examined cytokine productivity and associated signal transduction molecules in LPS-stimulated the monocytic cell line THP-1, under conditions of hyperglycemia. Differentiated THP-1 cells were cultured under normal and high glucose conditions without fetal bovine serum, and were stimulated with Escherichia coli LPS in the presence of LPS binding protein. Following stimulation, activated signal transduction molecules were detected by protein microarray and confirmed thereafter. Results indicated that c-jun N-terminal kinase (JNK) was highly-phosphorylated at high glucose concentrations, and this was confirmed by Western-immunoblotting. Tumor necrosis factor-α and monocyte chemo-attractant protein-1 production were significantly enhanced under these conditions. SP600125, a selective inhibitor of JNK, dose-dependently suppressed the production of these cytokine. Therefore, we suggest that this may be one of the mechanisms by which sub-clinical infection by Gram-negative bacteria promotes atherosclerosis in diabetic subjects.

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  • Gene Profiles during Root Canal Treatment in Experimental Rat Periapical Lesions Reviewed

    Zulema Rosalia Arias Martinez, Koji Naruishi, Keisuke Yamashiro, Fumio Myokai, Teruo Yamada, Kaori Matsuura, Naoko Namba, Hideo Arai, Junzo Sasaki, Yoshimitsu Abiko

    Journal of Endodontics   33 ( 8 )   936 - 943   2007.8

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  • Relationship of periodontal infection to serum antibody levels to periodontopathic bacteria and inflammatory markers in periodontitis patients with coronary heart disease Reviewed

    K. Yamazaki, T. Honda, H. Domon, T. Okui, K. Kajita, R. Amanuma, C. Kudoh, S. Takashiba, S. Kokeguchi, F. Nishimura, M. Kodama, Y. Aizawa, H. Oda

    Clinical & Experimental Immunology   149 ( 3 )   445 - 452   2007.7

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  • Oligonucleotide array analysis of cyclic tension-responsive genes in human periodontal ligament fibroblasts Reviewed

    Keisuke Yamashiro, Fumio Myokai, Koichi Hiratsuka, Tadashi Yamamoto, Kyoko Senoo, Hideo Arai, Fusanori Nishimura, Yoshimitsu Abiko, Shogo Takashiba

    The International Journal of Biochemistry & Cell Biology   39 ( 5 )   910 - 921   2007.1

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  • Regression of pustulosis palmaris et plantaris by periodontal treatment in a subject with severe periodontitis Reviewed

    Hiroshi Akazawa, Fushanori Nishimura, Hiroshi Maeda, Shogo Takashiba, Atsushi Mine, Kenji Maekawa, Takuo Kuboki

    International Journal of Dermatology   45 ( 12 )   1420 - 1422   2006.12

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  • Cloning and characterization of lipopolysaccharide-induced tumor necrosis factor α factor promoter Reviewed

    Nobuyuki Shiomi, Fumio Myokai, Koji Naruishi, Kosuke Oyaizu, Kyoko Senoo, Tomoko Yamaguchi, Salomon Amar, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   47 ( 3 )   360 - 368   2006.8

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  • Gene polymorphisms in periodontal health and disease. Reviewed International journal

    Shogo Takashiba, Koji Naruishi

    Periodontology 2000   40 ( 1 )   94 - 106   2006.2

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  • The regulatory effect of fermentable sugar levels on the production of leukotoxin by Actinobacillus actinomycetemcomitans Reviewed

    Katsunori Mizoguchi, Hiroyuki Ohta, Atsushi Miyagi, Hidemi Kurihara, Shogo Takashiba, Keijiro Kato, Yoji Murayama, Kazuhiro Fukui

    FEMS Microbiology Letters   146 ( 1 )   161 - 166   2006.1

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  • Anti-inflammatory effect of linear polarized infrared irradiation on interleukin-1β-induced chemokine production in MH7A rheumatoid synovial cells Reviewed

    Yasuko Shibata, Naomi Ogura, Keisuke Yamashiro, Shogo Takashiba, Toshirou Kondoh, Keiji Miyazawa, Masaru Matsui, Yoshimitsu Abiko

    Lasers in Medical Science   20 ( 3-4 )   109 - 113   2005.12

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  • α2 Integrin +807 Polymorphism in Drug-induced Gingival Overgrowth Reviewed International journal

    M. Ogino, J. Kido, M. Bando, N. Hayashi, C. Wada, T. Nagata, F. Nishimura, Y. Soga, S. Takashiba, T. Kubota, M. Itagaki, Y. Shimada, H. Tai, H. Yoshie, N. Yamazaki, Y. Shinohara, M. Kataoka

    Journal of Dental Research   84 ( 12 )   1183 - 1186   2005.12

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    α2 integrin on fibroblasts is reported to play an important role in the induction of drug-induced gingival overgrowth, which is characterized by excessive accumulation of type I collagen in gingival connective tissue. Silent polymorphism 807 T/C within the α2 integrin gene is associated with high/low α2 integrin expression. The aim of this study was to test the hypothesis that expression of α2 integrin 807 T/C polymorphism correlates with drug-induced gingival overgrowth. A case-control study comparing 136 subjects taking calcium channel blockers (72 with vs. 64 without drug-induced gingival overgrowth) demonstrated that the frequency of the +807 C allele was significantly higher in the case group than in the controls (odds ratio, 3.61; 95% confidence interval, 2.14 – 6.10; P &lt; 0.05). The present findings suggest that the α2 +807 C allele is one of the genetic risk factors for drug-induced gingival overgrowth.

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  • Isolation and Expression of FIP-2 in Wounded Pulp of the Rat Reviewed International journal

    M. Oyama, F. Myokai, T. Ohira, N. Shiomi, K. Yamashiro, H. Arai, F. Nishimura, S. Takashiba

    Journal of Dental Research   84 ( 9 )   842 - 847   2005.9

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    Pulpal wound healing followed by cavity preparation may involve reactionary or reparative dentinogenesis in relation to the cavity position; however, little is known about the molecular responses. We aimed to isolate and analyze genes induced or suppressed in the wounded pulp to identify molecular processes involved in the pulp responses to injury. Twenty-three cDNAs were isolated by cDNA subtraction between healthy and wounded pulp of rats. By library screening, we identified rat 14.7K-interacting protein (rFIP)-2A and B genes homologous to human FIP-2, being involved in regulating membrane trafficking and cellular morphogenesis. RT-PCR analysis showed induction for only rFIP-2B in the wounded pulp. In situ hybridization analysis revealed that both rFIP-2s were expressed strongly in condensing mesenchymal cells of the palatal process and surrounding Meckel’s cartilage, but not in intramembranous chondrogenic cells. Thus, up-regulated rFIP-2B expression may play a role in regulating membrane trafficking or cellular morphogenesis of these embryonic and wounded pulpal cells.

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  • Transcriptional regulation of β-defensin-2by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells Reviewed

    Junji Mineshiba, Fumio Myokai, Fumi Mineshiba, Kaori Matsuura, Fusanori Nishimura, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   45 ( 1 )   37 - 44   2005.7

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  • Periodontal Treatment in Severe Aplastic Anemia Reviewed International journal

    Kosuke Oyaizu, Fumi Mineshiba, Junji Mineshiba, Hirokazu Takaya, Fusanori Nishimura, Ichiro Tanimoto, Hideo Arai, Shogo Takashiba

    Journal of Periodontology   76 ( 7 )   1211 - 1216   2005.7

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    Background: Aplastic anemia (AA) is a rare hematologic disease characterized by hypo-cellular bone marrow. The clinical features include fatigue, increased bruising, and gingival bleeding caused by anemia, leukopenia, and thrombocytopenia. A patient with AA is at high risk for infection because of leukopenia. The risk of systemic infection is especially high in AA patients with severe local infections, including periodontitis. Accordingly, periodontal treatment should include antibiotic prophylaxis to reduce the risk of systemic infection. However, treatment of periodontitis in the AA patient is significantly complicated by the bleeding disorder. We present a case report of the successful periodontal treatment of an AA patient with spontaneous gingival bleeding.
    Methods: The patient was closely monitored for platelet and neutrophil counts before every treatment. The patient's platelet count was always under 10,000/mu l. Therefore, it was necessary to increase platelet counts to over 25,000/mu l by transfusion, after which subgingival scaling with anesthesia was performed. When the neutrophil count was less than 2,000/mu l, local minocycline chemotherapy was applied to the pockets. Periodontal infection was monitored by detection of bacterial DNA and measurement of serum immunoglobulin (Ig) G titer against periodontal bacteria.
    Results: Following the physical and chemical treatment, the gingival appearance improved dramatically and the spontaneous gingival bleeding disappeared. Moreover, the IgG titer against periodontal bacteria decreased to normal range and specific periodontal pathogens were no longer detectable in the tested pockets.
    Conclusion: We believe that the treatment strategy in the present report provides new sight into treatment planning for severely medically compromised patients.

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  • Role of helper T cells in the humoral immune responses against 53-kDa outer membrane protein from Porphyromonas gingivalis Reviewed

    N. Kato, H. Ohyama, F. Nishimura, S. Matsushita, S. Takashiba, Y. Murayama

    Oral Microbiology and Immunology   20 ( 2 )   112 - 117   2005.4

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  • Thiazolidinedione (Pioglitazone) Blocks P. gingivalis- and F. nucleatum, but not E. coli, Lipopolysaccharide (LPS)-induced Interleukin-6 (IL-6) Production in Adipocytes Reviewed International journal

    M. Yamaguchi, F. Nishimura, H. Naruishi, Y. Soga, S. Kokeguchi, S. Takashiba

    Journal of Dental Research   84 ( 3 )   240 - 244   2005.3

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    An elevated level of C-reactive protein (CRP) predicts the future development of coronary heart disease. Periodontitis appears to up-regulate CRP. CRP is produced by hepatocytes in response to interleukin-6 (IL-6). A major source of IL-6 in obese subjects is adipocytes. We hypothesized that lipopolysaccharide (LPS) from periodontal pathogens stimulated adipocytes to produce IL-6, and that the production was suppressed by the drugs targeted against insulin resistance, thiazolidinedione (pioglitazone), since this agent potentially showed an anti-inflammatory effect. Mouse 3T3-L1 adipocytes were stimulated with E. coli, P. gingivalis, and F. nucleatum LPS. The IL-6 concentration in culture supernatants was measured. All LPS stimulated adipocytes to produce IL-6. Although pioglitazone changed adipocyte appearance from large to small, and completely suppressed P. gingivalis and F. nucleatum LPS-induced IL-6 production, E. coli LPS-induced IL-6 production was not efficiently blocked. Thus, pioglitazone completely blocked periodontal-bacteria-derived LPS-induced IL-6 production in adipocytes, a major inducer of CRP.

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  • Detection of periodontal pathogenPorphyromonas gingivalisby loop-mediated isothermal amplification method Reviewed

    Hiroshi Maeda, Susumu Kokeguchi, Chiyo Fujimoto, Ichiro Tanimoto, Wakako Yoshizumi, Fusanori Nishimura, Shogo Takashiba

    FEMS Immunology & Medical Microbiology   43 ( 2 )   233 - 239   2005.2

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  • Long-term cyclosporin A exposure suppresses cathepsin-B and -L activity in gingival fibroblasts. Reviewed International journal

    Mayumi Yamaguchi, Koji Naruishi, Hisa Yamada-Naruishi, Kazuhiro Omori, Fusanori Nishimura, Shogo Takashiba

    Journal of periodontal research   39 ( 5 )   320 - 6   2004.10

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    BACKGROUND: Gingival overgrowth is a common side-effect following administration of cyclosporin A. We reported previously that lysosomal protease cathepsin-L activity, but not cathepsin-B, was significantly suppressed by short-term cyclosporin A exposure in human gingival fibroblasts. Although this suppression may lead to decreased degradation of gingival connective tissue, a net increase in matrix proteins, and gingival overgrowth, the effects of cyclosporin A need to be more elucidated, considering the long-term use for patients following organ transplantation. OBJECTIVE: The aim of the present study was to evaluate the effects of clinically relevant doses of cyclosporin A on cultured human gingival fibroblasts. We evaluated the effects of long-term cyclosporin A exposure on cell proliferation, mRNA expression of various proteases and both cathepsin-B and -L activity in human gingival fibroblasts. MATERIALS AND METHODS: Human gingival fibroblasts were isolated from three donors' healthy gingiva and cultured from five to eight passages with or without 200 ng/ml of cyclosporin A. Proliferative activity of cyclosporin A-treated cells was examined using MTT assay. Total RNA and cellular proteins were collected for semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis and for measurement of the cathepsin-B and -L activity. RESULTS: Long-term cyclosporin A exposure had no effects on cell proliferation. Accumulation of cathepsin-B, -H and -L mRNA was markedly suppressed by long-term cyclosporin A exposure, whereas accumulation of another lysosomal enzyme N-acetyl-beta-D-glucosaminidase mRNA, which is involved in remodeling of gingival epithelium, was not apparently impaired in cyclosporin A-treated cells. Accumulation of matrix metalloprotease-1 (MMP-1) and tissue inhibitor of matrix metalloprotease-1 (TIMP-1) mRNA, which are involved in remodeling of extracellular matrix, also was not impaired. In addition, we demonstrated that long-term cyclosporin A exposure significantly suppressed not only the activity of the active form of cathepsin-(B + L) compared to the activity in non-treated cells (p = 0.0458), but also the activity of the active form of cathepsin-B (p < 0.0001) in human gingival fibroblasts. CONCLUSION: The decreased ability of protein degradation by not only cathepsin-L but also cathepsin-B is, at least, one of the several factors developing the cyclosporin A-induced gingival overgrowth.

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  • Identification of Genes Differentially Regulated in Rat Alveolar Bone Wound Healing by Subtractive Hybridization Reviewed International journal

    T. Ohira, F. Myokai, N. Shiomi, K. Yamashiro, T. Yamamoto, Y. Murayama, H. Arai, F. Nishimura, S. Takashiba

    Journal of Dental Research   83 ( 7 )   546 - 551   2004.7

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    Periodontal healing requires the participation of regulatory molecules, cells, and scaffold or matrix. Here, we hypothesized that a certain set of genes is expressed in alveolar bone wound healing. Reciprocal subtraction gave 400 clones from the injured alveolar bone of Wistar rats. Identification of 34 genes and analysis of their expression in injured tissue revealed several clusters of unique gene regulation patterns, including the up-regulation at 1 wk of cytochrome c oxidase regulating electron transfer and energy metabolism, presumably occurring at the site of inflammation; up-regulation at 2.5 wks of pro-α-2 type I collagen involving the formation of a connective tissue structure; and up-regulation at 1 and 2 wks and down-regulation at 2.5 and 4 wks of ubiquitin carboxyl-terminal hydrolase l3 involving cell cycle, DNA repair, and stress response. The differential expression of genes may be associated with the processes of inflammation, wound contraction, and formation of a connective tissue structure.

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  • High Glucose Enhances Interleukin-6-induced Vascular Endothelial Growth Factor 165 Expression via Activation of Gp130-mediated p44/42 MAPK-CCAAT/Enhancer Binding Protein Signaling in Gingival Fibroblasts Reviewed

    Kazuhiro Omori, Koji Naruishi, Fusanori Nishimura, Hisa Yamada-Naruishi, Shogo Takashiba

    Journal of Biological Chemistry   279 ( 8 )   6643 - 6649   2004.2

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  • Systemic up-regulation of sTNFR2 and IL-6 in Porphyromonas gingivalis pneumonia in mice Reviewed

    Milan Petelin, Koji Naruishi, Nobuyuki Shiomi, Junji Mineshiba, Hideo Arai, Fusanori Nishimura, Shogo Takashiba, Yoji Murayama

    Experimental and Molecular Pathology   76 ( 1 )   76 - 81   2004.2

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  • CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects Reviewed

    Yoshihiko Soga, Fusanori Nishimura, Yoko Ohtsuka, Hiroaki Araki, Yoshihiro Iwamoto, Hisa Naruishi, Nobuyuki Shiomi, Yoshitomo Kobayashi, Shogo Takashiba, Kenji Shimizu, Yutaka Gomita, Eiji Oka

    Life Sciences   74 ( 7 )   827 - 834   2004.1

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  • C-Jun N-terminal kinase (JNK) inhibitor, SP600125, blocks interleukin (IL)–6-induced vascular endothelial growth factor (VEGF) production: cyclosporine A partially mimics this inhibitory effect Reviewed

    Koji Naruishi, Fusanori Nishimura, Hisa Yamada-Naruishi, Kazuhiro Omori, Mayumi Yamaguchi, Shogo Takashiba

    Transplantation   76 ( 9 )   1380 - 1382   2003.11

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  • Application of denaturing gradient gel electrophoresis (DGGE) to the analysis of microbial communities of subgingival plaque Reviewed

    C. Fujimoto, H. Maeda, S. Kokeguchi, S. Takashiba, F. Nishimura, H. Arai, K. Fukui, Y. Murayama

    Journal of Periodontal Research   38 ( 4 )   440 - 445   2003.8

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  • Gene Profiling in Human Periodontal Ligament Fibroblasts by Subtractive Hybridization Reviewed

    T. Yamamoto, F. Myokai, F. Nishimura, T. Ohira, N. Shiomi, K. Yamashiro, H. Arai, Y. Murayama, S. Takashiba

    Journal of Dental Research   82 ( 8 )   641 - 645   2003.8

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    Genes expressed by human periodontal ligament fibroblasts (HPFs) are likely to be associated with specific functions of the ligament. The aim of this study is to profile genes expressed highly by HPFs. A library (6 × 103pfu) was constructed, followed by subtraction of HPF cDNAs with human gingival fibroblast (HGF) cDNAs. Reverse-dot hybridization revealed that 33 clones expressed higher levels of specific mRNAs in HPFs than in HGFs. These were mRNAs for known genes, including several associated with maturation and differentiation of cells. None had been reported in PFs. One clone, PDL-29, identified as a COX assembly factor, showed much stronger mRNA expression in HPFs than in HGFs in culture. In rat periodontium, however, PDL-29 mRNA expression was similar in PFs and GFs. These results suggest that HPFs express many previously unreported genes associated with maturation and differentiation, but expression can differ in vitro and in vivo.

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  • Antimicrobial Periodontal Treatment Decreases Serum C-Reactive Protein, Tumor Necrosis Factor-Alpha, But Not Adiponectin Levels in Patients with Chronic Periodontitis Reviewed

    Yoshihiro Iwamoto, Fusanori Nishimura, Yoshihiko Soga, Kazu Takeuchi, Mikinao Kurihara, Shogo Takashiba, Yoji Murayama

    Journal of Periodontology   74 ( 8 )   1231 - 1236   2003.8

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  • Tumor necrosis factor-alpha gene (TNF-α) −1031/−863, −857 single-nucleotide polymorphisms (SNPs) are associated with severe adult periodontitis in Japanese Reviewed International journal

    Yoshihiko Soga, Fusanori Nishimura, Hideki Ohyama, Hiroshi Maeda, Shogo Takashiba, Yoji Murayama

    Journal of Clinical Periodontology   30 ( 6 )   524 - 531   2003.6

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    Objectives: Tumour necrosis factor-alpha (TNF-alpha ) and interleukin-1beta (IL-1beta ) participate in the establishment of inflammatory lesions in periodontitis. High production of these cytokines may relate to the severity of periodontitis. There have already been several studies examining the association between periodontitis and single nucleotide polymorphisms (SNPs) that affect cytokine productivity. Recently, new SNPs of TNF-alpha , -1031, -863 and -857, variants of which are observed in a relatively large proportion in Japanese, have been identified. The variant alleles of these SNPs have been suggested to be related to high TNF-alpha production. For a better understanding of the genetic factors associated with the severity of periodontitis, further analysis including these newly identified SNPs is essential. In addition, previous reports on TNF-alpha or IL-1beta SNPs associated with periodontitis were mainly for Caucasian populations. Therefore, the aim of this study is to examine the association between severe periodontitis in Japanese and the following SNPs: five in the TNF-alpha gene promoter (-1031, -863, -857, -308, -238) and three in the IL-1beta gene (-511, -31, +3953).
    Material and Methods: A total of 128 Japanese individuals were enrolled in this study. They were 64 patients with severe adult periodontitis and 64 healthy subjects. TNF-alpha and IL-1beta SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism for all subjects. TNF-alpha and IL-1beta production from LPS-stimulated monocytes/macrophages was also measured for 15 healthy male subjects.
    Results: TNF-alpha production in TNF-alpha -1031/-863 (linkage disequilibrated) or -857 SNP variant allele carriers tended to be elevated, and the frequency of subjects who carried at least one variant allele in TNF-alpha -1031, -863 or -857 SNPs among severe periodontitis patients was significantly higher than in healthy subjects.
    Conclusion: Since the frequency of subjects who carried at least one variant allele in TNF-alpha -1031, -863 or -857 SNPs was higher in periodontitis patients than in healthy subjects, TNF-alpha -1031, -863 and -857 SNPs appear to be associated with severe adult periodontitis in Japanese populations.

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  • Unique genes induced by mechanical stress in periodontal ligament cells Reviewed International journal

    Fumio Myokai, Masataka Oyama, Fusanori Nishimura, Taisuke Ohira, Tadashi Yamamoto, Hideo Arai, Shogo Takashiba, Yoji Murayama

    Journal of Periodontal Research   38 ( 3 )   255 - 261   2003.6

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    Objectives: The aim of this study is to isolate mechanical stress-induced genes (MSGens) from human periodontal ligament (PDL) cells and to analyze profiles of the mRNA expression of these genes.
    Background: Differential expression of genes in PDL cells under physiological stress such as occlusal force is thought to be orchestrated not only for the remodeling of PDL itself but also for the repair and regeneration of periodontal tissues. However, little is known about the genes expressed in PDL cells under mechanical stress.
    Methods: The cDNA from mechanical stress-applied human PDL cells was subtracted against the cDNA from static control cells. The subtracted cDNA was amplified by polymerase chain reaction (PCR) and cloned for further analysis.
    Results: Among 68 independent clones isolated, 15 contained DNA fragments greater than 250 bp. Reverse Northern analysis revealed a marked induction of MSGen-15 and MSGen-28 mRNA expression in the mechanical stress-applied cells. However, little difference in the magnitude of expression for the other MSGens was detected between the stress-applied cells and the control cells. After nucleotide sequencing and the analysis of homology with known genes, five clones were identified; ribosomal protein S27 (MSGen-9), MRG 15 (MSGen-15), androgen-binding protein (MSGen-18), cathepsin H (MSGen-28), and cytochrome c (MSGen-47). Interestingly, it has been reported that MRG 15 is a novel transcription factor involved in the regulation of cell growth and senescence. The remaining 10 clones, classified into six sequence types, had no significant homology with any known genes.
    Conclusions: These results suggest that many known and unknown genes are expressed in response to mechanical stress in PDL cells, and that a transcription factor, MRG 15, may be responsible for molecular events in PDL cells under mechanical stress.

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  • Ligation of IFN-γ-induced HLA-DR molecules on fibroblasts induces RANTES expression via c-Jun N-terminal kinase (JNK) pathway Reviewed

    Michio Meguro, Fusanori Nishimura, Hideki Ohyama, Shogo Takashiba, Yoji Murayama, Sho Matsushita

    Cytokine   22 ( 5 )   107 - 115   2003.6

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  • Antibacterial activity of synthetic human B defensin-2 against periodontal bacteria. Reviewed International journal

    Mineshiba F, Takashiba S, Mineshiba J, Matsuura K, Kokeguchi S, Murayama Y

    Journal of the International Academy of Periodontology   5 ( 2 )   35 - 40   2003.4

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    The oral epithelium is continuously exposed to a variety of microbial challenges that can cause infectious diseases such as periodontal disease. Human B Defensin-2 (hBD-2) is a cationic antimicrobial peptide with low molecular weight, which is inducible from oral epithelial cells upon either bacterial infection or stimulation with inflammatory cytokines. This peptide has a broad antimicrobial spectrum that includes gram-positive bacteria, gram-negative bacteria, and fungi. Therefore, it is thought that hBD-2 plays an important role as one of natural immunities to bacterial infection. However, its activity is inhibited by body fluids such as serum. The aim of this study was to assess the antibacterial activity of synthetic hBD-2 against oral bacteria in the presence of saliva or serum. The antibacterial activity of synthetic hBD-2 was tested against Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus mutans, and Escherichia coli. Antibacterial broth assay and diffusion assay were performed in vitro. The antibacterial activity of hBD-2 was approximately equal to that of minocycline at equimolar concentrations. Furthermore, the activity of hBD-2 remained at 60% in the presence of 80% saliva, whereas no activity remained in the presence of 20% serum. Our results suggest the possibility that synthetic hBD-2 could be useful to prevent infection by periodontal bacteria.

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  • Perspective of Cytokine Regulation for Periodontal Treatment: Fibroblast Biology Reviewed

    Shogo Takashiba, Koji Naruishi, Yoji Murayama

    Journal of Periodontology   74 ( 1 )   103 - 110   2003.1

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  • COUNTER-ANTIGEN PRESENTATION: FIBROBLASTS PRODUCE CYTOKINES BY SIGNALLING THROUGH HLA CLASS II MOLECULES WITHOUT INDUCING T-CELL PROLIFERATION Reviewed

    Hideki Ohyama, Fusanori Nishimura, Michio Meguro, Shogo Takashiba, Yoji Murayama, Sho Matsushita

    Cytokine   17 ( 4 )   175 - 181   2002.2

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  • T cell responses to major membrane protein II (MMP II) of Mycobacterium leprae are restricted by HLA-DR molecules in patients with leprosy Reviewed

    Hideki Ohyama, Sho Matsushita, Fusanori Nishimura, Nahoko Kato, Kentaro Hatano, Shogo Takashiba, Yoji Murayama

    Vaccine   20 ( 3-4 )   475 - 482   2001.11

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  • Subgingival microflora and antibody responses against periodontal bacteria of young Japanese patients with type 1 diabetes mellitus. Reviewed International journal

    Takahashi K, Nishimura F, Kurihara M, Iwamoto Y, Takashiba S, Miyata T, Murayama Y

    Journal of the International Academy of Periodontology   3 ( 4 )   104 - 111   2001.10

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    Periodontal disease is a complication of patients with type 1 diabetes mellitus (T1DM), although the mechanisms responsible for this relationship remain unclear. The aim of this study was to examine oral manifestations and the prevalence of periodontal pathogens from subgingival plaque samples and serum IgG antibody levels against them in young Japanese type 1 diabetic subjects. One hundred and seventeen Japanese T1DM subjects (53 male, 64 female, mean age +/- SD, 16 +/- 6.5 years) participated in this study. Thirty-nine periodontally healthy, age-matched nondiabetics served as controls. T1DM subjects were clinically assigned into three groups: 12 periodontitis, 32 gingivitis and 73 periodontally healthy. Microbiological tests for four periodontal pathogens, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia and Capnocytophaga ochracea were performed using 16S ribosomal RNA-based polymerase chain reaction methods. Serum IgG antibody levels against 12 periodontal bacteria including the four species assessed by polymerase chain reaction were measured by enzyme-linked immunosorbent assay. In the T1DM subjects, the Periodontitis group had a significantly longer mean duration of diabetes and a higher percentages of subjects harbouring P. gingivalis and P. intermedia than the Periodontally Healthy group. Serum IgG antibody levels against P. gingivalis were significantly elevated in the Periodontitis group compared with Gingivitis and Periodontally Healthy groups. These results indicate that Japanese T1DM subjects are a high-risk group for periodontal disease and both P. gingivalis infection and duration of T1DM are risk factors for the progression of periodontitis in patients with T1DM.

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  • Characterization of Two Genes Encoding Ferritin-Like Protein inActinobacillus actinomycetemcomitans Reviewed

    Masaru Hirosue, Susumu Kokeguchi, Hiroshi Maeda, Fusanori Nishimura, Shogo Takashiba, Yoji Murayama

    Microbiology and Immunology   45 ( 10 )   721 - 727   2001.10

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  • Impairment of Gingival Fibroblast Adherence by IL-6/sIL-6R Reviewed International journal

    K. Naruishi, S. Takashiba, F. Nishimura, H.-H. Chou, H. Arai, H. Yamada, Y. Murayama

    Journal of Dental Research   80 ( 5 )   1421 - 1424   2001.5

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    Interleukin-6 (IL-6) binds to human gingival fibroblasts (HGF) in the presence of a soluble form of IL-6 receptor (sIL-6R). We investigated the effects of IL-6 on the functions of HGF in the presence of sIL-6R. HGF changed their morphology from spindle-shaped to round, and detached from the culture dish by stimulation with IL-6/sIL-6R. In this condition, a signal transducer gpl30 and a transcription factor Stat3 were phosphorylated, resulting in activation of transcription factors Stat3 and C/EBPβ. Cytoskeletal β-actin and adhesion molecule integrin-a5, a subunit of α5β1 integrin (VLA-5), were found to possess potential binding domains for these transcription factors in their promoters. Accumulation of (3-actin and integrin-a5 mRNA decreased, contrary to the expectation of the induction of gene transcription. Furthermore, the decrease in their mRNAs was associated with reduced expression of both actin and VLA-5 proteins. These results suggest that the expression of VLA-5 and actin was down-regulated in HGF through an IL-6 signaling pathway, resulting in impairment of HGF adherence.

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  • Identification and characterization of B-cell epitopes of a 53-kDa outer membrane protein from Porphyromonas gingivalis Reviewed

    K. Oyaizu, H. Ohyama, F. Nishimura, H. Kurihara, S. Matsushita, H. Maeda, S. Kokeguchi, H. Hongyo, S. Takashiba, Y. Murayama

    Oral Microbiology and Immunology   16 ( 2 )   73 - 78   2001.4

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  • Serum phenytoin concentration and IgG antibody titre to periodontal bacteria in patients with phenytoin-induced gingival overgrowth. Reviewed International journal

    Yamada H, Nishimura F, Furuno K, Naruishi K, Kobayashi Y, Takashiba S, Murayama Y

    Journal of the International Academy of Periodontology   3 ( 2 )   42 - 47   2001.4

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    Epileptic patients taking phenytoin with gingival-overgrowth and those without gingival-overgrowth were compared for daily drug dose, plasma total phenytoin concentration, plasma free-phenytoin concentration and serum IgG antibody titre against 13 periodontal bacteria. Significantly higher daily drug dose was noted in patients with gingival overgrowth (P < 0.05) when compared with those without overgrowth. In addition, both total and free forms of plasma phenytoin concentration were significantly higher in sera of patients with gingival growth than of those without overgrowth (P < 0.01). Strong positive correlation was found between daily drug dose and serum phenytoin concentration in patients with gingival overgrowth, while weak correlation was found in patients without gingival overgrowth, suggesting a difference in drug metabolism in these two groups. However, no differences were found in serum IgG antibody titres to 13 periodontal bacteria examined between two groups. These results suggest that metabolic ability of phenytoin is one of the factors for developing gingival overgrowth, and that periodontal infection may not be a primary causative factor for gingival overgrowth but act as an additive factor which increase tissue mass for this unwanted side effect.

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  • Heterogeneity of Host Immunological Risk Factors in Patients With Aggressive Periodontitis Reviewed

    Keiso Takahashi, Hideki Ohyama, Michitaka Kitanaka, Takamasa Sawa, Junji Mineshiba, Fusanori Nishimura, Hideo Arai, Shogo Takashiba, Yoji Murayama

    Journal of Periodontology   72 ( 4 )   425 - 437   2001.4

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  • Immunopathological Diagnosis of Cicatricial Pemphigoid With Desquamative Gingivitis. A Case Report Reviewed

    Mikinao Kurihara, Fusanori Nishimura, Takashi Hashimoto, Ayako Komai, Hiroyoshi Ueda, Susumu Kokeguchi, Shogo Takashiba, Yoji Murayama

    Journal of Periodontology   72 ( 2 )   243 - 249   2001.2

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  • Tumor Necrosis Factor-α (TNF-α)-Induced and Interleukin-1β (IL-1β)-Induced Shedding of TNF Receptors from Gingival Fibroblasts Reviewed

    Hyogo Ohe, Shogo Takashiba, Koji Naruishi, Hsin-Hua Chou, Hisa Yamada, Fusanori Nishimura, Hideo Arai, Yoji Murayama

    Journal of Interferon & Cytokine Research   20 ( 12 )   1077 - 1082   2000.12

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    Tumor necrosis factor-alpha (TNF-alpha) exerts its functions by binding two different receptors (TNFR55 and TNFR75), Both TNFR55 and TNFR75 exist in cell-associated and soluble forms. Soluble TNF receptors (sTNFR), sTNFR55 and sTNFR75, are proteolytically shed upon inflammatory stimuli and then modulate various TNF-alpha bioactivities. As human gingival fibroblasts (HGF) can be potential targets for TNF-alpha in inflamed gingiva, we hypothesized that HGF partially modulate the cellular responses to TNF-alpha by regulating their own TNFR. In this study, the kinetics of expression of cell-associated and soluble forms of both receptors from cultured HGF in response to proinflammatory cytokines TNF-alpha and interleukin-1 beta (IL-1 beta) were investigated in vitro. Both TNF-alpha and IL-1 beta upregulated the gene expression of TNFR75 and did not affect that of TNFR55. TNF-alpha and IL-1 beta decreased binding of [I-125]TNF-alpha to HGF. Moreover, TNF-alpha and IL-1 beta upregulated the release of sTNFR75 from HGF but not that of sTNFR55, These results suggest that HGF under inflammatory conditions may contribute to the inactivation of circulating TNF-a through the preferential induction and shedding of TNFR75.

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  • Molecular characterization of the hlyX-like gene of Actinobacillus actinomycetemcomitans Y4 Reviewed International journal

    Susumu Kokeguchi, Masaru Hirosue, Hiroshi Maeda, Manabu Miyamoto, Shogo Takashiba, Yoji Murayama

    Research in Microbiology   151 ( 9 )   721 - 725   2000.11

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    We isolated and characterized a possible regulatory gene, designated actX gene, from Actinobacillus actinomyctemcomitans Y4, which defined the Actinobacillus pleuropneumoniae hlyX-like regulatory gene. DNA sequence analysis for plasmid clone pKM317 containing a 1.6-kb DNA insert indicated an open reading frame encoding a polypeptide of 257 amino acid residues. Analysis of the deduced amino acid sequence showed the presence of five characteristic cysteine residues in the N-terminal region and a putative DNA binding residue in the C-terminal region, indicating that actX might belong to a regulatory gene family. Escherichia coli DH5 alpha and a mutant strain JRG1728 transformed by plasmid carrying actX manifested apparent hemolytic activity on sheep blood agar and grew anaerobically, although the original strains did not. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

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  • Antibody responses against Porphyromonas gingivalis infection in patients with early-onset periodontitis Reviewed International journal

    Shujuan Guo, Keiso Takahashi, Susumu Kokeguchi, Shogo Takashiba, Denis F. Kinane, Yoji Murayama

    Journal of Clinical Periodontology   27 ( 10 )   769 - 777   2000.10

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    Background, aims: The aim of this study was to evaluate antibody responses against Porphyromonas gingivalis (P. gingivalis) infection in early-onset periodontitis (EOP) patients to elucidate further the host-parasite interactions in the pathogenesis of EOP.
    Method: 16 P. gingivalis-infected EOP and 20 adult periodontitis (AP) patients, and 18 periodontally healthy subjects (HS) participated in this study. Serum immunoglobulin G (IgG) antibody levels and avidities against extracted P. gingivalis whole cells were measured. The components of P. gingivalis outer membrane antigens (OMA) reacting to patients' sera were analysed from the molecular weights by Western blotting. Serum antibody levels against P. gingivalis lipopolysaccharide (LPS) were also measured. The ability of the patients' sera to block interleukin-1 beta (IL-1 beta) production by human mononuclear cells in response to P. gingivalis LPS was examined.
    Results: Antibody levels were positively correlated with antibody avidities in both EOP and AP patients (r=0.91, r=0.72, p&lt;0.0005, respectively), while not significantly so in HS (r=0.09). There was variability in the antigen recognition of P. gingivalis OMA in EOP and AP patients. Smear and 53-kDa protein were more frequently recognized by sera of EOP and AP patients rather than that of HS (p&lt;0.05). The smear was partly diminished by absorption with P. gingivalis LPS, indicating the smear antigen was partly composed of LPS. There was high correlation between antibody levels against P. gingivalis whole-cell extracts and LPS in EOP and AP patients (r=0.81, p=0.0002, r=0.87, p&lt;0.0001, respectively), while not significant in HS (r=0.22). The sera of EOP and AP patients with high IgG titre to P. gingivalis LPS blocked IL-1 beta production more effectively than that of the patients with low IgG titre to P. gingivalis LPS.
    Conclusions: These results indicate that EOP patients' antibody response against P. gingivalis infection does not differ significantly from that of AP patients. The person-to-person heterogeneous antibody production against P. gingivalis LPS could contribute to our understanding of the relationship between the defensive ability of EOP patients and their chronic infection with this pathogen.

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  • Induction of Intracellular Interleukin-1 β Signals via Type II Interleukin-1 Receptor in Human Gingival Fibroblasts Reviewed International journal

    H.-H. Chou, S. Takashiba, H. Maeda, K. Naruishi, F. Nishimura, H. Arai, H.-k. Lu, Y. Murayama

    Journal of Dental Research   79 ( 9 )   1683 - 1688   2000.9

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    The type II interleukin-1 receptor (IL-1RII) has been thought to be incapable of transducing signals to cells because of its short intracellular domain, while type I IL-1 receptor (IL-1RI) does transduce signals. Since over-expression of IL-1RII has been demonstrated to inhibit cytokine production in the fibroblastic cell line, it has been proposed to use IL-1RII to prevent IL-1-induced inflammation in connective tissue. In this study, trace amounts of IL-1RII mRNA expression were detected in human gingival fibroblasts (HGFs), which are affected by cytokines in inflammatory periodontal disease. Cloning of the cDNA encoding IL-1RII expressed in HGFs revealed 3 amino acid substitutions in the extracellular domain, when compared with the 408 residues predicted from human B-cells. Over-expression of IL-1RII on HGFs by gene transfer down-regulated the expression of IL-1β mRNA and IL-6 mRNA in response to IL-1β stimulation, while the expression of IL-8 mRNA was not affected. In the IL-1RII-transfected HGFs, phosphorylation of 25-and 74-kDa proteins was up-regulated upon IL-1β stimulation in the transfected HGFs. The phosphorylation of these proteins was suppressed by the addition of a neutralizing antibody against IL-1RII. These results suggest that the IL-1RII may regulate HGFs expression of cytokine mRNA upon IL-1β stimulation, possibly by altering the IL-1RI-dependent signals.

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  • High Glucose Suppresses Cathepsin Activity in Periodontal-ligament-derived Fibroblastic Cells Reviewed International journal

    F. Nishimura, K. Naruishi, H. Yamada, T. Kono, S. Takashiba, Y. Murayama

    Journal of Dental Research   79 ( 8 )   1614 - 1617   2000.8

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    The accumulation of extracellular matrices and integrins by high glucose has been reported in relation to diabetic complications. We previously reported that PDL cells expressed a higher amount of VLA-5 when cultured in high-glucose (4500 mg/L) medium than those cultured in low-glucose (1100 mg/L) medium. In this study, we aimed to address (1) whether this effect was mediated by the transcriptional level of the gene or the degradative level of the protein, and (2) whether this effect was mediated by TGF-β. The results indicated that the level of mRNA encoding a5 integrin did not change in PDL cells regardless of the concentration of glucose. Alternatively, high glucose suppressed cathepsin B+L activity. Additionally, the level of mRNA encoding TGF-β was not affected by high glucose, nor did an anti-TGF-β neutralizing antibody have an effect on the expression of β5 gene or cathepsin activity. Therefore, the effects of high glucose appeared to be mediated by impaired protein degradation, but not by autocrine TGF-β.

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  • Epitope mapping of heat shock protein 60 (GroEL) fromPorphyromonas gingivalis Reviewed

    Hiroshi Maeda, Manabu Miyamoto, Susumu Kokeguchi, Takayuki Kono, Fusanori Nishimura, Shogo Takashiba, Yoji Murayama

    FEMS Immunology & Medical Microbiology   28 ( 3 )   219 - 224   2000.7

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  • Development of 16S rDNA-based PCR assay for detecting Centipeda periodontii and Selenomonas sputigena Reviewed

    S. Sawada, S. Kokeguchi, S. Takashiba, Y. Murayama

    Letters in Applied Microbiology   30 ( 6 )   423 - 426   2000.6

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  • Phenytoin and Cyclosporin A Suppress the Expression of MMP-1, TIMP-1, and Cathepsin L, But Not Cathepsin B in Cultured Gingival Fibroblasts Reviewed International journal

    Hisa Yamada, Fusanori Nishimura, Koji Naruishi, Hsin-Hua Chou, Shogo Takashiba, George M. Albright, Salvador Nares, Anthony M. Iacopino, Yoji Murayama

    Journal of Periodontology   71 ( 6 )   955 - 960   2000.6

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    Background: Fibroblasts are known not only to synthesize and secrete extracellular matrix proteins, but also to degrade them for connective tissue remodeling. Drug-induced gingival overgrowth is characterized by a massive accumulation of extracellular matrix components in gingival connective tissues. Although some previous reports suggested that causative drugs stimulated the fibroblast proliferation, the results are not conclusive yet. In this study, we hypothesized that drug-induced gingival overgrowth could be a consequence of impaired ability of matrix degradation rather than an enhanced proliferation of gingival fibroblasts induced by these drugs.
    Methods: Normal human gingival fibroblasts were cultured with or without either 20 mug/ml of phenytoin or 200 ng/ml of cyclosporin A. Total RNA and cellular proteins were collected every day for RT-PCR analyses and for measuring lysosomal enzyme activity. In addition, an immunohistochemical study was performed to detect lysosomal enzymes in cells from enlarged gingiva of the patients with phenytoin-induced gingival overgrowth.
    Results: RT-PCR analyses revealed that these drugs suppressed the expression of MMP-1, TIMP-1, and cathepsin L, but not that of cathepsin B in a time-dependent manner. Then, we measured the activity of lysosomal enzymes and cathepsin B and L. The results indicated that although cathepsin B activity was not observed to be impaired, regardless of the drugs used in these cells, both total and active forms of combined activity of cathepsins B and L were suppressed in a time-dependent manner.
    Conclusions: The results indicate that, besides suggested effects of these drugs on gingival fibroblasts and/or on accumulated cells in the gingival tissues, extracellular matrix-degrading ability, particularly that by cathepsin L, is also suppressed by cyclosporin A and phenytoin in gingival fibroblasts, and that lysosomal enzyme plays an important role in the pathogenesis of drug-induced gingival hyperplasia.

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  • Cell Surface-Associated Enolase inActinobacillus actinomycetemcomitans Reviewed

    Hiroaki Hara, Hiroyuki Ohta, Tetsuyoshi Inoue, Toshio Ohashi, Shogo Takashiba, Yoji Murayama, Kazuhiro Fukui

    Microbiology and Immunology   44 ( 5 )   349 - 356   2000.5

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  • Differentiation of Monocytes to Macrophages Primes Cells for Lipopolysaccharide Stimulation via Accumulation of Cytoplasmic Nuclear Factor κB Reviewed International journal

    Shogo Takashiba, Thomas E. Van Dyke, Salomon Amar, Yoji Murayama, Aubrey W. Soskolne, Lior Shapira

    Infection and Immunity   67 ( 11 )   5573 - 5578   1999.11

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    <title>ABSTRACT</title>
    During infection, circulating blood monocytes migrate from the vasculature to the extravascular compartments where they mature into tissue macrophages. The maturation process prepares the cell to actively participate in the inflammatory and the immune responses, and many transcription factors have been found to be involved. Here we report on a novel role for nuclear factor κB (NF-κB) in this process. Its accumulation in the cytoplasm of differentiated macrophages is responsible for the enhanced ability of the cell to respond to lipopolysaccharide (LPS) stimulation, as determined by tumor necrosis factor alpha (TNF-α) secretion. Differentiation of the human monocytic cell line THP-1 into macrophage-like cells was induced by exposure of the cells to phorbol myristate acetate. DNA-bindable NF-κB was not detected in the cytoplasm of undifferentiated THP-1 cells but accumulated in the cytoplasm of the cells following differentiation. No TNF-α was detected in the media of resting differentiated and nondifferentiated THP-1 cells. Stimulation with LPS of differentiated cells induced the production of higher levels of TNF-α than stimulation of nondifferentiated cells. This hyperresponsiveness to LPS was found in the mRNA and secreted TNF-α levels. Furthermore, stimulation with LPS induced the translocation of NF-κB from the cytoplasm into the nucleus. This translocation process was more rapid in the differentiated cells than in the nondifferentiated cells, and the resultant accumulated levels of NF-κB in the nucleus were higher. The DNA-bindable NF-κB was identified as a heterodimer of p65 and p50. The results suggest that NF-κB accumulation in the cytoplasm during maturation of monocytes to macrophages primes the cells for enhanced responsiveness to LPS and results in the rapid secretion of inflammatory mediators, such as TNF-α, by mature macrophages following LPS challenge.

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  • Identification by Subtractive Hybridization of a Novel Insertion Sequence Specific for Virulent Strains of Porphyromonas gingivalis Reviewed International journal

    Koichi Sawada, Susumu Kokeguchi, Hiroshi Hongyo, Satoko Sawada, Manabu Miyamoto, Hiroshi Maeda, Fusanori Nishimura, Shogo Takashiba, Yoji Murayama

    Infection and Immunity   67 ( 11 )   5621 - 5625   1999.11

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    <title>ABSTRACT</title>

    Subtractive hybridization was employed to isolate specific genes from virulent
    <italic>Porphyromonas gingivalis</italic>
    strains that are possibly related to abscess formation. The genomic DNA from the virulent strain
    <italic>P. gingivalis</italic>
    W83 was subtracted with DNA from the avirulent strain ATCC 33277. Three clones unique to strain W83 were isolated and sequenced. The cloned DNA fragments were 885, 369, and 132 bp and had slight homology with only
    <italic>Bacillus stearothermophilus</italic>
    IS
    <italic>5377</italic>
    , which is a putative transposase. The regions flanking the cloned DNA fragments were isolated and sequenced, and the gene structure around the clones was revealed. These three clones were located side-by-side in a gene reported as an outer membrane protein. The three clones interrupt the open reading frame of the outer membrane protein gene. This inserted DNA, consisting of three isolated clones, was designated IS
    <italic>1598</italic>
    , which was 1,396 bp (i.e., a 1,158-bp open reading frame) in length and was flanked by 16-bp terminal inverted repeats and a 9-bp duplicated target sequence. IS
    <italic>1598</italic>
    was detected in
    <italic>P. gingivalis</italic>
    W83, W50, and FDC 381 by Southern hybridization. All three
    <italic>P. gingivalis</italic>
    strains have been shown to possess abscess-forming ability in animal models. However, IS
    <italic>1598</italic>
    was not detected in avirulent strains of
    <italic>P. gingivalis</italic>
    , including ATCC 33277. The IS
    <italic>1598</italic>
    may interrupt the synthesis of the outer membrane protein, resulting in changes in the structure of the bacterial outer membrane. The IS
    <italic>1598</italic>
    isolated in this study is a novel insertion element which might be a specific marker for virulent
    <italic>P. gingivalis</italic>
    strains.

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  • HLA genetics for diagnosis of susceptibility to early-onset periodontitis Reviewed International journal

    Shogo Takashiba, Hideki Ohyama, Kosuke Oyaizu, Nahoko Kogoe-Kato, Yoji Murayama

    Journal of Periodontal Research   34 ( 7 )   374 - 378   1999.10

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    Human leukocyte antigens (HLA) are essential in the recognition of foreign antigens in humoral immune response, which is genetically predetermined. Susceptibility to certain diseases that involve the immune response has been studied in relation to distinct HLA types. Although some diseases have been found Co correlate to specific HLA loci positively, it has been difficult to isolate HLA types that predispose patients to periodontal destruction. Here. we review the current knowledge and recent advances in HLA genetics and its biology, which determine susceptibility to early-onset periodontitis (EOP). The HLA-DRB1*1501-DQB1*0602 genotype has been found with increasing frequency in EOP patients. This HLA genotype expresses aspartic acid at position 57 and glycine at position 70 on the DQ beta chain, suggesting a capability to bind certain bacterial antigens. The T cell response against the outer membrane protein (Ag53) of Porphyromonas against gingivalis was examined via this HLA genotype. Strong T cell response against Ag53 p141-161 was inhibited partially by anti-DR antibody, but not by anti-DQ antibody, possible host and bacterial peptides capable of binding DRB1*1501 were elucidated when the peptide sequence was compared to gene and protein databases. These results suggest that patients who have the HLA-DRB1*1501-DQB1*0602 genotype may have an accelerated T cell response to certain periodontapathic bacteria such as P. gingivalis in hyperimmune reactions and thus increased susceptibility to EOP.

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  • Role of soluble interleukin-6 receptor in inflamed gingiva for binding of interleukin-6 to gingival fibroblasts Reviewed International journal

    Koji Naruishi, Shogo Takashiba, Hsin-Hua Chou, Hideo Arai, Fusanori Nishimura, Yoji Murayama

    Journal of Periodontal Research   34 ( 6 )   296 - 300   1999.8

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    Interleukin-6 (IL-6), frequently detected in periodontitis, is known to mediate important signals in the inflammatory cytokine network. Gingival fibroblasts (GF) secrete cytokines upon stimulation with inflammatory mediators. However, it is not clear if GF respond to IL-6. We examined the lL-6 receptor gene expression in GF. Furthermore, we tested whether GF are target cells for IL-6 by examination of binding of IL-6. GF were found to contain trace amounts of mRNA for IL-6 receptor (IL-GR), but had high levels of mRNA for 130-kDa glycoprotein (gp130), which is a signal transducer for IL-6/IL-6R complex. Based on this observation, we hypothesized that IL-6 could bind GF if exogenous soluble forms of IL-6R (sIL-6R) existed in the gingiva or culture condition. Thus, we investigated the existence of sIL-6R in gingiva using enzyme-linked immunosorbent assay and whether sIL-6R influenced the binding of IL-6 to GF in vitro. In inflamed gingiva, sIL-6R was detected and its concentration ranged from 150 to 700 pg/mu g protein. The sIL-6R enhanced the binding of IL-6 to GF in a dose-dependent manner. This enhancement was inhibited by an antibody against gp130, suggesting that the IL-6/sIL-6R complex bound to the fibroblasts via gp130. These data demonstrated that gingival fibroblasts can be target cells for IL-6 in the presence of appropriate amounts of sIL-6R. This situation may exist during inflammation in periodontal tissue.

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  • A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor   gene expression: Molecular cloning, sequencing, characterization, and chromosomal assignment Reviewed

    F. Myokai, S. Takashiba, R. Lebo, S. Amar

    Proceedings of the National Academy of Sciences   96 ( 8 )   4518 - 4523   1999.4

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  • In Vitro Induction of Activation-Induced Cell Death in Lymphocytes from Chronic Periodontal Lesions by Exogenous Fas Ligand Reviewed International journal

    Takamasa Sawa, Fusanori Nishimura, Hideki Ohyama, Keiso Takahashi, Shogo Takashiba, Yoji Murayama

    Infection and Immunity   67 ( 3 )   1450 - 1454   1999.3

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    <title>ABSTRACT</title>
    Periodontitis is a chronic inflammatory disease which gradually destroys the supporting tissues of the teeth, leading to tooth loss in adults. The lesions are characterized by a persistence of inflammatory cells in gingival and periodontal connective tissues. To understand what mechanisms are involved in the establishment of chronic lesions, we hypothesized that infiltrating lymphocytes might be resistant to apoptosis. However, both Bcl-2 and Bcl-xL were weakly detected in lymphocytes from the lesions, compared with those from peripheral blood, suggesting that these cells are susceptible to apoptosis. Nevertheless, very few apoptotic cells were observed in tissue sections from the lesions. Lymphocytes from the lesions expressed mRNA encoding Fas, whereas Fas-ligand mRNA was very weakly expressed in lymphocytes from the lesions and in periodontal tissues. Since the results indicated that lymphocytes in the lesions might be susceptible to Fas-mediated apoptosis but lack the death signal, we next investigated if these lymphocytes actually undergo apoptosis by the addition of anti-Fas antibodies in vitro. Fas-positive lymphocytes from the lesions underwent apoptosis by these antibodies, but Fas-negative lymphocytes and Fas-positive peripheral lymphocytes did not undergo apoptosis by these antibodies. These results indicate that lymphocytes in the lesions are susceptible to activation-induced cell death and are induced to die by apoptosis after the addition of exogenous Fas ligand.

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  • Phylogenetic characterization of Centipeda periodontii, Selenomonas sputigena and Selenomonas species by 16S rRNA gene sequence analysis Reviewed International journal

    S Sawada, S Kokeguchi, F Nishimura, S Takashiba, Y Murayama

    MICROBIOS   98 ( 391 )   133 - 140   1999

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    The nearly complete 16S rRNA gene sequences for oral Gram-negative anaerobic motile bacteria, Centipeda periodontii, Selenomonas sputigena and Selenomonas species (formerly S. sputigena type strain), were determined in order to unveil their relationship to other oral motile bacteria. To determine the phylogenetic characterization of these bacteria, their 16S rRNA gene sequences were obtained and compared with those from the ribosomal sequence databases previously reported. The 16S rRNA gene sequences of these bacteria were similar to those of Selenomonas ruminantium and Schwartzia succinivorans isolated from rumens, and to Pectinatus cerevisiiphilus isolated from spoiled beer. Among oral bacteria, the nucleotide sequence analysis of these bacteria revealed high nucleotide similarity to Veillonella species, whereas low similarity to oral motile bacteria such as Campylobacter species. Phylogenetic analysis clearly confirmed that C. periodontii and two Selenomonas species were classified as relatives of a group besides Selenomonas, Schwartzia, and Pectinatus species, and not as close relatives to oral motile bacteria, such as Campylobacter species. These results suggest that such oral Gram-negative anaerobic motile bacteria are close relatives of oral bacteria.

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  • T cell responses to 53-kDa outer membrane protein of porphyromonas gingivalis in humans with early-onset periodontitis Reviewed International journal

    Hideki Ohyama, Sho Matsushita, Nahoko Kato, Fusanori Nishimura, Kosuke Oyaizu, Susumu Kokeguchi, Hidemi Kurihara, Shogo Takashiba, Yasuharu Nishimura, Yoji Murayama

    Human Immunology   59 ( 10 )   635 - 643   1998.10

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    Patients with early-onset periodontitis (EOP) are susceptible to infection with periodontopathic bacteria, such as Porphyromonas gingivalis. Ag53, 53-kDa outer membrane protein of P. gingivalis, evokes strong humoral immune responses in EOP patients. In a first step to clarify how host immune cells recognize Ag53, we established Ag53-specific short-term T cell lines from 22 subjects including 6 EOP patients and 16 healthy donors, using overlapping peptides based on Ag53 amino acid sequences. All T cell lines from active EOP patients recognized a common region (p141-181, especially p141-161) on Ag53, while those from healthy donors showed heterogeneous specificity. p141-181 was not recognized by T cell lines established from EOP patients following therapy. A monoclonal antibody to HSA-DRB1 inhibited Ag53-induced proliferation of most of the T cell lines. Our observations suggest that, although antigen-presenting molecules are common in EOP patients and in healthy individuals, p141-161 includes a major T cell epitope(s) on Ag53 for active EOP patients but not for healthy individuals or inactive EOP patients. (C) American Society for Histocompatibility and Immunogenetics, 1998 Published by Elsevier Science Inc.

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  • The S-layer protein fromCampylobacter rectus: sequence determination and function of the recombinant protein Reviewed International journal

    Manabu Miyamoto, Hiroshi Maeda, Michitaka Kitanaka, Susumu Kokeguchi, Shogo Takashiba, Yoji Murayama

    FEMS Microbiology Letters   166 ( 2 )   275 - 281   1998.9

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    The gene encoding the crystalline surface layer (S-layer) protein from Campylobacter rectus, designated sip, was sequenced and the recombinant gene product was expressed in Escherichia coli. The gene consisted of 4086 nucleotides encoding a protein with 1361 amino acids. The N-terminal amino acid sequence revealed that Sip did not contain a signal sequence, but that the initial methionine residue was processed. The deduced amino acid sequence displayed some common characteristic features of S-layer proteins previously reported. A homology search showed a high similarity to the Campylobacter fetus S-layer proteins, especially in their N-terminus. The C-terminal third of Sip exhibited homology with the RTX toxins from Gram-negative bacteria via the region including the glycine-rich repeats. The Sip protein had the same N-terminal sequence as a 104-kDa cytotoxin isolated from the culture supernatants of C. rectus. However, neither native nor recombinant Sip showed cytotoxicity against HL-60 cells or human peripheral white blood cells. These data support the idea that the N-terminus acts as an anchor to the cell surface components and that the C-terminus is involved in the assembly and/or transport of the protein. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.

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  • Periodontal disease as a complication of diabetes mellitus. Reviewed International journal

    Nishimura F, Takahashi K, Kurihara M, Takashiba S, Murayama Y

    Annals of periodontology / the American Academy of Periodontology   3 ( 1 )   20 - 29   1998.7

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    Based on our clinical observations that patients with insulin-dependent diabetes mellitus (IDDM) are subject to periodontal disease, we developed the hypothesis that hyper- or hypoglycemia might contribute to the pathogenesis of diabetic periodontitis. In this article, experimental facts that substantiate this hypothesis are presented on the basis of our studies and then discussed. Hyperglycemia progressively glycates body proteins, forming advanced glycation end products (AGE), which stimulate phagocytes to release inflammatory cytokines such as TNF-alpha and IL-6. In this context, to understand the effects of hyperglycemic episodes on periodontal health, 24 adolescent IDDM patients were examined for their periodontal status, and 3 of them were found to have periodontitis. Laboratory analyses on these 3 patients revealed that 2 had elevated serum TNF-alpha levels. These results may partly support the current hypothesis of a mechanism of diabetic complications in which abnormal cytokine levels induced by AGE could exacerbate inflammatory responses. In IDDM patients, the diabetes is often accompanied not only by hyperglycemic episodes but also by iatrogenic hypoglycemia. Periodontal ligament cells (PDL) cultured under hyperglycemic conditions were impaired in such biological functions as adhesion and motility, while cells cultured under hypoglycemic conditions (10 mg/dL) gradually dissociated from their anchor and underwent cell death. These phenomena correlated well with the expression profile of fibronectin receptor. Interestingly, these changes due to the different glucose levels were observed more intensively in PDL than in other fibroblastic cells, suggesting that the biological functions of PDL are easily led to impairment by variation or rapid fluctuation of glucose levels. These observations suggest that hyperglycemia could indirectly exacerbate inflammatory tissue destruction through the body's scavenger system against AGE, and that both hyper- and hypoglycemia might directly impair the biological functions of periodontal connective tissues through cell-matrix interactions.

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  • Identification of a novel insertion sequence element from Porphyromonas gingivalis W83 Reviewed

    K Sawada, S Kokeguchi, H Hongyo, S Sawada, M Hirosue, C Fujimoto, T Wataki, A Shimizu, T Katayama, E Kawabata, M Miyamoto, S Takashiba, Y Murayama

    JOURNAL OF DENTAL RESEARCH   77 ( 5 )   1299 - 1299   1998.5

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  • Comparative study of two outer membrane protein genes from Porphyromonas gingivalis Reviewed International journal

    H Hongyo, S Kokeguchi, H Kurihara, M Miyamoto, H Maeda, S Takashiba, Y Murayama

    MICROBIOS   95 ( 381 )   91 - 100   1998

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    A periodontal pathogen, Porphyromonas gingivalis possesses either a 53 kD (Ag53) or a 67 kD (Ag67) outer membrane protein (OMP). Almost all sera from patients with periodontal diseases reacted strongly with either Ag53 or Ag67. In previous work the cloning and sequencing of the 53 kD outer membrane protein gene designated pga53 from Fl gingivalis FDC381, was reported and the presence of a gene homologous to pga53 in Fl gingivalis ATCC 33277 demonstrated. In the present work this pga53-homologous gene from Fl gingivalis ATCC 33277 was isolated and characterized. Nucleotide sequence analysis revealed that this gene encoded Ag67, and the gene was designated pga67. The deduced amino acid sequence and composition of pga67 was similar to the amino acid composition and N-terminal partial sequence of Ag67. An open reading frame of pga67 consisted of 1,692 nucleotides encoded as 564 amino acids, including a 49 amino acid signal sequence. The comparative analysis between pga67 and pga53 revealed that (1) the deduced amino acid sequence showed a 30.1% homology; (2) signal sequence and proline-rich regions at the C-terminus were the most conserved regions; (3) considerable differences were found mainly in the middle part of the OMPs; and (4) obvious differences in the two-dimensional models were evoked. These differences between pga67 and pga53 may explain the antigenic diversity between Ag67 and Ag53 OMPs.

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  • Characteristics of outer membrane protein of Actinobacillus actinomycetemcomitans grown with maltose. Reviewed

    S Kokeguchi, M Miyamoto, H Maeda, H Hongyo, M Hirosue, K Sawada, S Takashiba, Y Murayama

    JOURNAL OF DENTAL RESEARCH   77   985 - 985   1998

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  • Host Defensive, Immunological, and Microbiological Observations of an Early-Onset Periodontitis Patient With Virus-Associated Hemophagocytic Syndrome Reviewed

    Takayuki Kono, Masayuki Takigawa, Fusanori Nishimura, Shogo Takashiba, Masatsugu Nakagawa, Hiroshi Maeda, Hideo Arai, Atsushi Nagai, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   68 ( 12 )   1223 - 1230   1997.12

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    VIRUS-ASSOCIATED HEMOPHAGOCYTIC SYNDROME (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses; 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels cn. Ip, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.

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  • Comparison of in vitro proliferative capacity of human periodontal ligament cells in juvenile and aged donors Reviewed International journal

    F. Nishimura, V. P. Terranova, M. Braithwaite, R. Orman, H. Ohyama, J. Mineshiba, H. H. Chou, S. Takashiba, Y. Murayama

    Oral Diseases   3 ( 3 )   162 - 166   1997.9

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    OBJECTIVE: The aim of this study is to compare the in vitro proliferative capacity of periodontal ligament (PDL) cells from aged and juvenile donors. MATERIALS AND METHODS: Flow-cytometric analysis of the cell cycle was used to compare the length of each cell cycle, and the ratio of the cells progressing through the cycles between four PDL cells from juvenile donors and four cells from aged donors. Then, replicative capacity of the PDL cells from three juvenile and three aged donors was compared by serial cultures. Finally, expression of c-fos was compared between cells proliferating and cells which had reached senescent. RESULTS: Flow- cytometric analysis of the cell cycle had revealed that although there were no differences in the length of each phase of the cell cycle, significant differences were found in the ratio of the cells entering from Gap I to DNA synthesis phase of the cell cycle (P &lt
    0.025). Replicative capacity was much longer in two cells from juvenile donors (about 20 population doublings), while all cells from aged donors showed short dividing abilities (less than eight population doublings), hence entered senescent phases shortly. Additionally, no c-fos was detected in cells which had reached senescence upon stimulation with serum. CONCLUSIONS: It is generally believed that aged humans have an impaired wound healing ability. We believe that more fibrotic PDL tissues seen in aged humans might be the reason for this, and suggest that this phenomena might be due to the progressive accumulation of senescent cell populations.

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  • Effect of TNF-α on DNA Synthesis and Extracellular Matrix Protein Synthesis in Human Gingival Fibroblasts

    Higuchi Yutaka, Takigawa Masayuki, Arai Hideo, Washio Norifumi, Ohe Hyogo, Nishimura Fusanori, Shimizu Hideki, Nomura Yoshio, Takashiba Shogo, Murayama Yoji

    Journal of the Japanese Association of Periodontology   39 ( 2 )   264 - 272   1997.6

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    Tumor necrosis factor-α (TNF-α) is one of proinflammatory cytokines produced as early inflammatory responses, and is suggested to participate in the establishment of inflammatory lesions. To understand the regulatory role of TNF-α on periodontal connective tissue, we evaluated the effect of TNF-α on DNA synthesis, collagenous and non-collagenous protein synthesis, prostaglandin E_2 (PGE_2) productivity, and platelet-derived growth factor (PDGF)-A chain mRNA expression in human gingival fibroblasts (HGF). Results indicated that 1) TNF-α promoted DNA synthesis, both collagenous and non-collagenous protein synthesis in HGF, 2) TNF-α markedly enhanced PGE_2 production in HGF, 3) inhibition of PGE_2 synthesis by the addition of indomethacin, further augmented the ability of DNA synthesis and collagenous and non-collagenous protein synthesis in HGF, and 4) TNF-α enhanced the expression of PDGF-A chain mRNA in HGF. These results suggest that TNF-α enhances the DNA synthesis and extracellular matrix protein synthesis in HGF, but endogenous PGE_2 which is induced by TNF-α, partially blocks these effects. Furthermore, the enhancement of DNA synthesis in response to TNF-α could be possibly mediated by autocrine PDGF.

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  • Molecular cloning and characterization of the gene encoding 53 kD outer membrane protein of Porphyromonas gingivalis Reviewed International journal

    H Hongyo, H Kurihara, S Kokeguchi, M Miyamoto, H Maeda, M Hayakawa, Y Abiko, S Takashiba, Y Murayama

    MICROBIOS   92 ( 370 )   47 - 57   1997

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    The pga53 gene which encoded the antigenic 53 kD outer membrane protein (Ag53) was isolated from a genomic DNA library of Porphyromonas gingivalis FDC381 by using an Ag53-immunized rabbit serum. Determination of its complete nucleotide sequence revealed that the precursor of Ag53 had a 50 amino-acid putative signal sequence and the mature protein of 448 amino acids. The deduced amino acid sequence after a 50 amino-acid putative signal sequence was in complete agreement with the first 20 N-terminal amino acids of purified Ag53. Analysis of the deduced amino acid sequence revealed the presence of a highly hydrophilic proline-rich region at the C-terminal of Ag53. The deduced amino acid sequence showed 29.9% homology with that of a 72 kD cell-surface protein in P. gingivalis. Southern hybridization revealed that pga53 was specific to several P. gingivalis strains and that P. gingivalis strains which did not possess Ag53 had genes homologous to pga53.

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  • A regulatory gene controlling growth of Actinobacillus actinomycetemcomitans. Reviewed

    S Kokeguchi, M Miyamoto, H Maeda, H Hongyo, M Hirosue, HH Chou, F Nishimura, H Arai, S Takashiba, Y Murayama

    JOURNAL OF DENTAL RESEARCH   76   1683 - 1683   1997

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  • Inhibition of nuclear factor kappa B subunit p65 mRNA accumulation in lipopolysaccharide-stimulated human monocytic cells treated with sodium salicylate Reviewed

    S. Tokashiba, T. E. Dyke, S. Amar

    Oral Microbiology and Immunology   11 ( 6 )   420 - 424   1996.12

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  • HLA Class II Genotypes Associated With Early-Onset Periodontitis: DQB1 Molecule Primarily Confers Susceptibility to the Disease Reviewed International journal

    Hideki Ohyama, Shogo Takashiba, Kosuke Oyaizu, Atsushi Nagai, Taeko Naruse, Hidetoshi Inoko, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   67 ( 9 )   888 - 894   1996.9

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    DNA TYPING WAS PERFORMED on 24 Japanese patients with early-onset periodontitis (EOP) using the PCR-RFLP method to investigate an association of the susceptibility to EOP with the particular HLA class II alleles (HLA-DRB1, -DQA1, and -DQB1), DRB1*1401, DRB1*1501, DQB1*0503, and DQB1*0602 were found more frequently (''susceptible'') in the EOP patients than in healthy controls. In contrast, DRB1*0405 and DQB1*0401 were found less frequently (''resistant'') in EOP patients, All patients carrying DQB1*0602 had an atypical BamHI site in the intron upstream of the third exon of the DQB1 gene, which in our previous studies appeared to be a susceptible marker for EOP. A comparative analysis of the amino acid sequences of these susceptible and resistant HLA-DRB1 and DQB1 alleles elucidated some differences in antigen-derived peptide binding sites related to the susceptible or resistant alleles. Especially, DQB1*0503 and DQB1*0602 alleles carrying aspartic acid at position 57 and glycine at position 70 are increased significantly in EOP. Since amino acid residues at positions 57 and 70 on the DQB1 molecule are supposed to be involved in antigen binding, amino acid substitutions at these positions may affect the immune responsiveness to the periodontopathic antigen. Our results suggest that the DQB1 molecule plays a crucial role in the pathogenesis of EOP and that the susceptibility to EOP may be determined by the binding ability between the peptide and HLA-DQ antigens.

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  • Host Defensive Functions in a Family Manifesting Early-Onset Periodontitis Reviewed International journal

    Hideo Arai, Toshihiro Chihara, Keiso Takahashi, Atsushi Nagai, Isao Akutsu, Shogo Takashiba, Fusanori Nishimura, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   67 ( 4 )   433 - 442   1996.4

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    FAMILY CASE STUDIES HELP US IDENTIFY host risk factors in periodontal disease. In this study we examine a family consisting of a mother (40 years old, with rapidly progressive periodontitis), her elder daughter (14 years old, with localized juvenile periodontitis), and younger daughter (13 years old, with simple gingivitis). We examined 1) the peripheral neutrophil functions (chemotactic migration, phagocytosis, superoxide production); 2) lymphocyte functions (proliferative activity and cytokine productivity of T cells, immunoglobulin [Ig] M productivity of B cells when stimulated with pokeweed mitogen); 3) phenotypic analyses of peripheral lymphocyte subpopulations; 4) serum IgG antibody titers against periodontopathic bacteria; and 5) serological type of HLA class IS. All the subjects exhibited high T4/T8 ratios due to high percentage of CD4-positive cells, showed high IgG titers to Actinobacillus actinomycetemcomitans, and had a HLA DQw1 in common. The mother showed a slight deficiency of neutrophil chemotactic migration to N-formyl methyonyl leucyl phenylalanin (fMLP), raised interleukin-2 productivity of T cell, and high levels of IgG titers to Porphyromonus gingivalis and Fusobacterium nucleatum. Both daughters showed weak T cell proliferative response to anti-CD3 monoclonal antibody and low IgM productivity. Low lymphocyte responsiveness may be involved in the pathogenesis of periodontal disease of these daughters; therefore, the lymphocyte dysfunctions shown should be considered in relation to the progression of periodontal disease.

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  • Clinical and Laboratory Studies on a Patient With Early Onset Periodontitis and Her Family Members. A Case Report Reviewed

    Keiso Takahashi, Masayuki Takigawa, Hiroaki Hara, Atsushi Nagai, Shogo Takashiba, Fusanori Nishimura, Toshihiro Chibara, Hideki Ohyama, Nobuhiko Satoh, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   66 ( 5 )   403 - 412   1995.5

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  • Lipopolysaccharide-inducible and salicylate-sensitive nuclear factor(s) on human tumor necrosis factor alpha promoter Reviewed International journal

    S Takashiba, T E Van Dyke, L Shapira, S Amar

    Infection and Immunity   63 ( 4 )   1529 - 1534   1995.4

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    Lipopolysaccharide (LPS) is one of the most potent trigger substances for monocytes and macrophages causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. The nature of the nuclear factors involved in human TNF-alpha gene regulation is still unknown. Nuclear factor kappa B (NF-kappa B) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with LPS. However, it remains unclear whether these nuclear factors are the only ones involved in human TNF-alpha gene regulation. In this report, to further the identification of nuclear factor(s) involved in TNF-alpha gene regulation, human monocytic THP-1 cells were transfected with a series of truncated versions of human TNF-alpha promoter. A 98-bp region located from nucleotides -584 to -487 demonstrated strong promoter activity. Electrophoretic mobility shift assays demonstrated that a 64-bp fragment located within the 98-bp region and lacking any potential NF-kappa B-binding sites avidly bound LPS-challenged THP-1 nuclear protein. Although this binding was inhibited in salicylate-treated cells, as was binding of NF-kappa B, the pattern of binding was found to differ from that noted for NF-kappa B. Analysis of this 64-bp fragment disclosed the absence of an NF-kappa B consensus sequence, suggesting a novel nuclear DNA-binding protein necessary for the initiation of human TNF-alpha transcription other than, or in addition to, NF-kappa B.

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  • Prostaglandin E2 Inhibits Interleukin-6 Release But Not Its Transcription in Human Gingival Fibroblasts Stimulated With Interleukin-1β or Tumor Necrosis Factor-α Reviewed

    Masayuki Takigawa, Shogo Takashiba, Keiso Takahashi, Hideo Arai, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   65 ( 12 )   1122 - 1127   1994.12

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    INFLAMMATORY MEDIATORS PRODUCED BY HUMAN GINGIVAL FIBROBLASTS (HGF) have been implicated in the initiation and progression of periodontal disease. The purpose of this study was to examine whether prostaglandin E(2) (PGE(2)), which is produced in abundance from HGF after stimulation with interleukin (IL)-1 beta or tumor necrosis factor-alpha (TNF-alpha), could regulate IL-6 production by HGF. HGF stimulated with either IL-1 beta or TNF-alpha showed a rapid and dose-dependent increase in IL-6 mRNA accumulation and IL-6 secretion, as demonstrated by reverse transcription-polymerase chain reaction analysis and bioassay. IL-6 secretion from either IL-1 beta- or TNF-alpha-stimulated HGF was enhanced by the inhibition of PGE(2) synthesis with indomethacin. Furthermore, the addition of PGE(2) inhibited IL-6 secretion from these cells. In contrast, indomethacin or PGE(2) did not affect the accumulation of IL-6 mRNA in IL-1 beta-stimulated HGF. These data indicate that IL-6 production by HGF is up-regulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that this production may be partially down-regulated by endogenous and exogenous PGE(2) at the post-transcriptional level.

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  • Cytokine-Dependent Synergistic Regulation of Interleukin-8 Production From Human Gingival Fibroblasts Reviewed International journal

    Masayuki Takigawa, Shogo Takashiba, Fumio Myokai, Keiso Takahashi, Hideo Arai, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   65 ( 11 )   1002 - 1007   1994.11

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    HUMAN GINGIVAL FIBROBLASTS (HGF) may have an important role in the orchestration of immuno participant cells infiltrating the gingiva in response to continuously recurring bacterial infection. To examine the cytokine network regulating HGF-derived interleukin (IL)-8, a potent neutrophil chemotactic cytokine, we analyzed the effects of inflammatory cytokines alone and iii combination on IL-8 production by HGF. IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), Interferon-gamma (IFN-gamma), IL-6, and IL-8 were used as stimulants. HGF secreted IL-8 in a dose-dependent manner after stimulation with either IL-1 beta or TNF-alpha, but not with IFN-gamma or IL-6. Furthermore, IL-8 itself did not affect IL-8 mRNA accumulation in HGF in an autocrine manner, The combination of IL-1 beta and TNF-alpha synergistically enhanced the secretion of IL-8, whereas IFN-gamma suppressed IL-8 secretion by IL-1 beta- or TNF-alpha-stimulated HGF. These effects were also observed at each level of IL-8 mRNA expression in HGF. IL-8 secretion by cytokine-stimulated HGF was not influenced my the inhibition of PGE(2) synthesis with indomethacin, indicating that endogenous PGE(2) was not involved in IL-8 production by HGF. These results indicate that IL-8 production by HGF is synergistically stimulated by specific cytokines, IL-1 beta and TNF-alpha, and suggest that these stimulatory effects are down-regulated by IFN-gamma at the transcriptional let ei through PGE(2)-independent pathways. Thus, neutrophil-mediated processes in periodontal disease may be regulated in part by HGF in the cytokine network of immuno-participant cells.

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  • Molecular Basis of Leukocyte Adhesion Molecules in Early-Onset Periodontitis Patients With Decreased CD11/CD18 Expression on Leukocytes Reviewed International journal

    Kyoko Katsuragi, Shogo Takashiba, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   65 ( 10 )   949 - 957   1994.10

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    WE ANALYZED THE CELL-CELL ADHERENCE RELATED to CD11/CD18 and CD18 mRNA in individuals with decreased CD11/CD18 expression on their neutrophil surface. Epstein Barr virus-transformed B cell lines were developed from one localized juvenile periodontitis (LJP) patient with decreased CD11/CD18 in the peripheral blood neutrophils and without systemic diseases; two siblings with generalized prepubertal periodontitis (GPP) caused by leukocyte adhesion deficiency (LAD); another LJP patient; one localized prepubertal periodontitis (LPP) patient; and two healthy subjects. Adhesion of leukocytes to each other was measured as cluster formation by aggregation assay. The length and the amount of CD18 mRNA expressed in the cell lines were analyzed by Northern blotting using the P-32-labeled CD18 cDNA. The coding region of the mRNA was analyzed by the reverse transcription-polymerase chain reaction method. Base-mismatches between CD18 mRNA and the P-32-labeled RNA probe synthesized from CD18 cDNA were analyzed by RNase protection assay. In the adherence assay, cells from the LJP patients with decreased CD11/CD18 formed more clusters of smaller size and fewer cells than those of the other subjects. The cells from GPP and LAD patients did not aggregate and did not form clusters either in the absence or presence of PMA. There were no differences in the length and the amount of mRNA between the LJP patients and the other subjects, while GPP-LAD patients expressed a small amount of long mRNA. The whole coding region (2,313 base pairs) of all subjects was amplified except for the GPP-LAD patients, and the 5'-region (1,119 base pairs) was amplified from all subjects. Base-mismatches were detected on the coding region from 965 to 1,450 nucleotides of CD18 mRNA in GPP-LAD patients. No mismatch was detected on other regions of CD18 mRNA in any subject. These results suggest that the LJP patient with an anomaly of qualitative aggregation related to CD11/CD18 is not related to sequence abnormalities of CD18 mRNA suggesting other mechanisms. In contrast, the adherence defect in two GPP-LAD patients was related to heterogeneous molecular mutations on CD18.

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  • An Atypical Site In HLA-DQb1 Detected in Leprosy Patients Reviewed

    H OHYAMA, A NAGAI, S TAKASHIBA, K SUGIYAMA, S INOUE, M MIZUSHIMA, A KOHZUMA, Y MURAYAMA

    INTERNATIONAL JOURNAL OF LEPROSY AND OTHER MYCOBACTERIAL DISEASES   62 ( 2 )   293 - 294   1994.6

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  • Unique Intronic Variations of HLA-DQβ Gene in Early-Onset Periodontitis Reviewed International journal

    Shogo Takashiba, Sumihare Noji, Fusanori Nishimura, Hideki Ohyama, Hidemi Kurihara, Yoshio Nomura, Shigehiko Taniguchi, Yoji Murayama

    Journal of Periodontology   65 ( 5 )   379 - 386   1994.5

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    HUMAN LEUKOCYTE ANTIGEN (HLA) class II beta chain plays an important role in the recognition of foreign antigens in immune reactions. Different forms of immune reaction may be concerned with initiation and progression of infectious diseases such as periodontitis. In this study we examined the frequency of HLA class II serotype and the variation of HLA class II beta gene in periodontitis patients. HLA serotypic frequencies in 70 Japanese patients with periodontitis and 26 individuals with periodontal health were examined. No HLA serotype specific to any type of periodontitis was observed. In order to detect differences among some HLA serotypes, restriction fragment length polymorphism (RFLP) analysis was undertaken with cDNA probes for HLA-DR beta and HLA-DQ beta genes in 20 subjects (15 patients and 5 healthy individuals). Atypical BamHI and EcoRI restriction sites were found in the HLA-DQ beta gene from 3 patients with early-onset periodontitis. In addition to these 20 subjects, an additional 80 subjects (40 patients and 40 healthy individuals) were screened for the atypical BamHI restriction site using the polymerase chain reaction method. It was detected in 7 patients with early-onset periodontitis, 1 patient with adult periodontitis, and 3 healthy subjects. No clinical differences except age were found between patients with this gene variation and other patients. Interestingly, all 3 healthy subjects with this gene variation were from subjects whose family members developed early-onset periodontitis with the gene variation. Atypical BamHI and EcoRI restriction sites and 41-nt repeated sequence were found in the intron before the third exon of HLA-DQB gene. These results suggest that these intronic gene variations may be useful as gene markers for a subpopulation of early-onset periodontitis and might affect immune reactions such as antigen recognition.

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  • Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor Reviewed International journal

    L. Shapira, S. Takashiba, S. Amar, T. E. Dyke

    Oral Microbiology and Immunology   9 ( 2 )   112 - 117   1994.4

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    The purpose of this study was to investigate factors influencing the ability of lipopolysaccharide (LPS) derived from Porphyromonas gingivalis to elicit secretion of tumor necrosis factor-alpha (TNFalpha) from human monocytes (adherent mononuclear cells). The results indicate that P gingivalis LPS stimulation of TNFalpha from monocytes is comparable to LPS from Escherichia coli. Both LPS, although structurally different, increased TNFalpha secretion in a dose-dependent manner. In serum-free conditions, TNFalpha secretion was relatively low, but it dramatically increased at human serum concentrations as low as 1%. Maximal secretion was observed in the presence of 10% serum, with a slight decrease at higher serum concentrations. The CD14 molecule is a putative monocyte LPS receptor. When cells were pre-incubated with a blocking monoclonal antibody (My4) to CD14, TNFalpha-mRNA accumulation and TNFalpha secretion were reduced to control levels at LPS concentrations of up to 10 ng/ml. At higher LPS concentrations, the blocking effect was only partial, in spite of 50-fold excess antibody concentration. The blocking effect was observed only in the presence of serum. The effect of the CD14 antibody was dose-dependent with saturation at 2.5 mug/ml. The results suggest that CD14 is one of the major receptors for P gingivalis LPS but highlight the necessity to investigate other cell-surface receptors mediating P gingivalis-LPS interactions. These interactions are believed to be important in the pathogenesis of periodontal destruction.

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  • Role of Cytokine in the Induction of Adhesion Molecules on Cultured Human Gingival Fibroblasts Reviewed International journal

    Keiso Takahashi, Masayuki Takigawa, Shogo Takashiba, Atsushi Nagai, Manabu Miyamoto, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   65 ( 3 )   230 - 235   1994.3

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    THIS STUDY WAS UNDERTAKEN IN AN EFFORT to understand the role of cytokines on human gingival fibroblasts and T lymphocyte trafficing into inflamed gingival tissue. Using flow cytometry we examined gingival fibroblasts to determine the level of cell surface expression and the percentage of cells positive for intercellular adhesion molecule 1 (ICAM-1), the HLA-DR antigen, lymphocyte function-associated antigen 3 (LFA-3), and the CD44 molecule, which are involved in antigen presentation. The following cytokines were used: interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, and IL-8. The levels of ICAM-1 expression were enhanced in a dose- and time-dependent manner by IL-1 beta, TNF-alpha, or IFN-gamma, but not by IL-6 or IL-8. HLA-DR surface expression was induced only by IFN-gamma in a dose- and time-dependent manner, but not by the other cytokines tested. In contrast, the expression of LFA3 and the CD44 molecule could be detected without the stimulation of any cytokine, but the levels of their expression were not significantly changed by any cytokines. The enhanced ICAM-1 expression by cytokines was reduced in a time-dependent manner following the removal of cytokines from the reaction mixture, while IFN-gamma-induced HLA-DR expression was maintained even 7 days after the removal of IFN-gamma. These data support an interactive role for inflammatory cytokines and the expression of adhesion molecules on gingival fibroblasts in the pathogenesis of gingival inflammation in periodontal disease.

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  • Assessment of Interleukin-6 in the Pathogenesis of Periodontal Disease Reviewed International journal

    Keiso Takahashi, Shogo Takashiba, Atsushi Nagai, Masayuki Takigawa, Fumio Myoukai, Hidemi Kurihara, Yoji Murayama

    Journal of Periodontology   65 ( 2 )   147 - 153   1994.2

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    THIS STUDY WAS PERFORMED TO INVESTIGATE the aspects of interleukin-6 (IL-6) production in both the gingival tissue and the peripheral blood of patients with periodontal disease and of periodontally healthy subjects. In addition, IL-6 expression in human gingival tissues was studied by reverse transcription-polymerase chain reaction analysis and by immunoperoxidase staining with anti-IL-6 monoclonal antibody. The levels of IL-6 in the culture supernatants from peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide and in serum were examined by bioassay. We detected IL-6 mRNA expression in all inflamed gingival tissues (17/17) examined and in 2/4 in healthy gingival tissues. IL-6 protein was detected mainly in endothelial cells, fibroblasts, and macrophages but not in the area containing T or B cells in the inflamed gingival tissues, and was not detected at all in healthy gingival tissues. There was no significant difference between the subjects with periodontal disease and those with healthy gingival tissues either in serum IL-6 levels or in the amount of IL-6 produced by PBMC. These results suggest that non-lymphoid cells in inflamed gingival tissue may contribute to the pathogenesis of periodontal disease via IL-6 production, and that the IL-6 produced in gingival tissue may not reflect the IL-6 levels in peripheral blood. 3.

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  • LEUKOCYTE ADHESION MOLECULES CD11/CD18 AND THEIR ROLE IN PERIODONTAL-DISEASES Reviewed

    Y MURAYAMA, K KATSURAGI, S TAKASHIBA, H KURIHARA

    MOLECULAR PATHOGENESIS OF PERIODONTAL DISEASE   215 - 233   1994

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  • Cloning and characterization of human TNFα promoter region Reviewed International journal

    Shogo Takashiba, Lior Shapira, Salomon Amar, Thomas E. Van Dyke

    Gene   131 ( 2 )   307 - 308   1993.9

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    We report the sequence of a 1.2-kb human tumor necrosis factor alpha (TNFalpha) promoter region, which was cloned using PCR. The sequence has several variations from two previous reports and exhibits many potential DNA-binding sites specific to mammalian gene regulatory proteins inducible by lipopolysaccharides.

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  • Rapid fluorometric quantificaition of monocyte attachment in tissue culture wells Reviewed International journal

    Lior Shapira, Shogo Takashiba, John R. Kalmar, Thomas E. Van Dyke, Vivian Barak, W. Aubrey Soskolne

    Journal of Immunological Methods   165 ( 1 )   93 - 98   1993.9

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    A simple fluorometric assay that permits rapid quantification of attachment of monocytes or macrophages in tissue culture wells is described. Using 4,6-diamidino-2-phenylindole (DAPI) as a specific fluorochrome marker for DNA, we observed a dose-dependent increase with strong linear correlation in fluorescent emission over a broad range of DNA concentrations. Measurements of the DNA content of the human monocytic cell line THP-1 demonstrated a linear correlation between fluorescence intensity and cell number from 5 x 10(4) to 1 x 10(6) cells, with an estimated average DNA content of 7.5 pg DNA per cell. While untreated THP-1 cells were not detectably adherent, PMA induction for 24 h results in 57-76% adherence to plastic surface. This method was found to be useful for measuring the number of peripheral blood monocytes separated from lymphocytes by attachment. 16 subjects were sampled and the standard deviation of each individual did not exceed 10%. The number of attached cells was between 10-16% of the total mononuclear cells. Fluorescence measurement of DNA with DAPI permits rapid and accurate determination of cell numbers and appears useful in the quantification of adherent populations such as myelocytic cells and cell lines.

    DOI: 10.1016/0022-1759(93)90110-s

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  • Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha Reviewed International journal

    S Takashiba, M Takigawa, K Takahashi, F Myokai, F Nishimura, T Chihara, H Kurihara, Y Nomura, Y Murayama

    Infection and Immunity   60 ( 12 )   5253 - 5258   1992.12

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    Inflammatory mediators produced by cells in the gingiva have been implicated in the initiation and progression of periodontal disease, a common infectious disease. In this study, we examined the biological activity of neutrophil chemotactic factors and the kinetics of expression of interleukin-8 (IL-8) mRNA derived from normal gingival fibroblasts in response to inflammatory mediators in an in vitro model. Gingival fibroblasts stimulated by either recombinant human interleukin-1 beta or recombinant human tumor necrosis factor alpha produced neutrophil chemotactic factors after 4 h, whereas expression of cell-derived IL-8 mRNA was detected within 1 h after stimulation. Furthermore, in a neutralization assay, rabbit anti-recombinant human IL-8 antiserum inhibited neutrophil chemotactic activity to basal levels. These results provide evidence that gingival fibroblasts synthesize potent chemotactic factors such as IL-8 in the presence of the inflammatory mediators interleukin-1 beta and tumor necrosis factor alpha. The activity of these factors may contribute to neutrophil-mediated processes in the pathogenesis of periodontal disease.

    DOI: 10.1128/iai.60.12.5253-5258.1992

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  • Host Defense Findings in a Single Family Manifesting Early-Onset Periodontitis

    CHIHARA Toshihiro, NAGAI Atsushi, AKUTSU Isao, HONGYO Hiroshi, TAKAHASHI Keiso, SHIMIZU Naoko, TANIMOTO Ichiro, SHIMABUKU Osamu, FUJITA Naoko, MIYAMOTO Manabu, TAKASHIBA Shogo, GOTO Hiroyuki, NISHIMURA Fusanori, ISOSHIMA Osamu, SHIMIZU Hideki, KURIHARA Hidemi, NOMURA Yoshio, MURAYAMA Yoji

    Journal of the Japanese Association of Periodontology   34 ( 1 )   204 - 212   1992.3

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    Assessments of host defense functions were made in a woman and her two daughters, all of whom manifested early-onset periodontitis (rapidly progressive periodontitis in the mother; localized juvenile periodontitis in the elder daughter; gingivitis in the younger daughter). The analyses of peripheral neutrophil functions revealed depressed neutrophil chemotaxis in the mother. Phenotypic and functional analyses of peripheral lymphocytes showed an elevated percentage of CD 4^+ cells and T 4/T 8 ratios in all subjects, and a depressed lymphocyte proliferative response to stimulation with CD 3 antibody in the younger daughter. Serological typing of HLA antigens revealed that the mother and one of the daughters had some class II HLA phenotypes in common. Serum IgG antibody levels to Actinobacillus actinomycetemcomitans were elevated in all subjects, those to Porphyromonas gingivalis in the mother and younger daughter, and those to Fusobacterium nucleatum in the mother. The pathogenesis of periodontal disease in individual members of this family could not be clarified solely from the results of the host defense functions examined. Other factors in the host defense network must be taken into consideration.

    DOI: 10.2329/perio.34.204

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    Other Link: http://search.jamas.or.jp/link/ui/1993025574

  • Studies on the Status of Periodontal Disease from the Lymphocytes Functions Concerned with Immunoglobulin Synthesis

    TAKAHASHI Keiso, NAGAI Atsushi, AKUTSU Isao, SATO Nobuhiko, TAKASHIBA Shogo, MIYAMOTO Manabu, TAKIGAWA Masayuki, MYOKAI Fumio, KATSURAGI Kyoko, HASHIMOTO Toshiaki, NOMURA Yoshio, MURAYAMA Yoji

    Journal of the Japanese Association of Periodontology   33 ( 3 )   685 - 694   1991.9

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    Language:Japanese   Publisher:The Japanese Society of Periodontology  

    The purpose of these studies was to assess the relationship between factors in the immune network concerned with immunoglobulin synthesis. We examined immunoglobulin production, lymphocyte subset ratios and lymphocyte function using peripheral blood mononuclear cells from 50 subjects consisting of 32 patients with periodontal disease and 18 periodontally healthy subjects. On the basis of serum antibody titers to periodontal bacteria, patients were classified into two groups characterized by either low or high titers. Patients had lower proportional counts of suppressor/cytotoxic T cells and higher immunoglobulin productivity than healthy subjects. Subjects with an elevated or decreased ratio of lymphocyte subsets and lymphocyte functions were detected more frequently among patients, irrespective of antibody titers. However, a wide distribution of values was observed among subjects in all of the examination. Based on the results obtained, it appears that lymphocyte functions concerned with humoral immune response vary widely among subjects, and each feature must be clarified individually.

    DOI: 10.2329/perio.33.685

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    Other Link: http://search.jamas.or.jp/link/ui/1993066054

  • A Family Study of a Mother and Daughter with Increased Susceptibility to Early-Onset Periodontitis: Microbiological, Immunological, Host Defensive, and Genetic Analyses Reviewed International journal

    Fusanori Nishimura, Atsushi Nagai, Keiji Kurimoto, Osama Isoshima, Shogo Takashiba, Mitsuharu Kobayashi, Isao Akutsu, Hidemi Kurihara, Yoshio Nomura, Yoji Murayama, Hiroyuki Ohta, Keijiro Kato

    Journal of Periodontology   61 ( 12 )   755 - 765   1990.12

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    Microbiological, immunological, host-defensive, and genetic analyses were performed on a mother and daughter, both of whom had early-onset periodontitis (rapidly progressive periodontitis in the mother; localized juvenile periodontitis in the daughter). Microscopic examination revealed a greatly elevated percentage of rod-form bacteria in both subjects. Fusobacterium sp. and Porphyromonas gingivalis (formerly Bacteroides gingivalis) were the predominant microorganisms cultured. The humoral immune responses to F. nucleatum, P. gingivalis, and Actinobacillus actinomycetemcomitans were much higher in both subjects than those to any other periodontal bacteria examined. Functional and phenotypic analysis of the peripheral lymphocytes showed no significant abnormalities. However, investigation of neutrophil function showed that the mother had depressed neutrophil chemotaxis and superoxide production. The daughter had depression not only of chemotaxis and superoxide production, but also of neutrophil phagocytosis. Serological typing of HLA antigens revealed the same Class II HLA profile in both subjects. It was concluded that both subjects very probably had an identical condition and that these patients provided a unique model for improving our understanding of the host factors involved in periodontal disease.

    DOI: 10.1902/jop.1990.61.12.755

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  • Periodontal Therapy by Local Delivery of Minocycline : Clinical Study of Periodontal Therapy by LS-007

    KURIMOTO Keiji, ISOSHIMA Osamu, NAORA Yuka, ANADA Takashi, KOBAYASHI Yoshitomo, KOBAYASHI Mitsuharu, ARAI Hideo, TAKASHIBA Shogo, NANBA Hideki, YOKOYAMA Masayuki, MITSUDA Yuka, MIZUSHIMA Yumi, NOMURA Yoshio, MURAYAMA Yoji, UEDA Masatoshi, TERANISHI Yoshihiro, FUJIWARA Kazuyuki, HASHIZUME Akiko, KAMAYA Shinpei, HOSOYAMA Yoko, UEBA Kenji, ONISHI Kazuyuki, SHIRAI Takeo, OHASHI Satoshi, HIGASHI Hirosuke, KIOKA Yoshifumi, MINAMIBAYASHI Shigeyoshi, TANAKA Mayumi, KITAMURA Takuya, MAKIGUSA Kazuto, YAMAOKA Akira, URAGUCHI Ryoji, HAGIWARA Satsuki, FUKUDA Mitsuo, ODA Sigeru, LIN Cherng-Jong, TAKEFUTA Wataru, MERA Toyotsune, MINEGISHI Daizou, UMEDA Makoto, NAKAMOTO Hiroshi, INATOMI Hirofumi, Narongsak Laosrisin, NOGUCHI Toshihide, ISHIKAWA Isao

    Journal of the Japanese Association of Periodontology   30 ( 1 )   191 - 205   1988.3

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    Our previous studies have been performed to establish methods for local delivery of Minocycline hydrochloride (MINO: Lederle Japan, LTD, Tokyo) in a therapy for periodontal disease. This study was done clinically to evaluate the effectiveness, safety, and usefulness of a LS-007 medicine containing 2 percent titers of MINO. Forty five periodontitis patients (119 teeth) with periodontal pockets (≧4mm) participated in this study. The experimental systems were evaluated by comparing microbiological and clinical effectiveness of LS-007, placebo, and Minocycline tablet (Lederle Japan, LTD). The results were as follows, 1. The effectiveness of LS-007 was examined in two delivery system; in one system the medicine was redelivered after one week, and in the other system after two weeks. Both systems revealed similar effectiveness until after two weeks from the last delivery. 2. When LS-007 was delivered once in a week for 4 successive weeks, LS-007 demonstrated its effectiveness until after 4 weeks from the last delivery. 3. A pretreatment with scaling prior to the application of LS-007 raised the effectiveness of LS-007. 4. The systemic delivery of Minomycine tablet demonstrated microbiologically and clinically similar effect to the local delivery of LS-007. In the systemic delivery, however, there was a subject who suffered harmful side effect of the medicine. From these results, we concluded the local delivery of LS-007 was clinically effective, safe, and useful as a therapy for periodontal disease.

    DOI: 10.2329/perio.30.191

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    Other Link: http://search.jamas.or.jp/link/ui/1989131026

  • POLYMORPHISM OF COMPROMISED HOSTS IN PERIODONTITIS PATIENTS Reviewed

    S TAKASHIBA, F NISHIMURA, M KOBAYASHI, A NAGAI, AKUTSU, I, K OKAMURA, O ISOSHIMA, H KURIHARA, Y NOMURA, Y MURAYAMA

    RECENT ADVANCES IN CLINICAL PERIODONTOLOGY   790   383 - 386   1988

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  • Studies on Microflora and Host Defensive Function of a Mother and Daughter with Early Onset Periodontitis

    NISHIMURA Fusanori, NAGAI Atsushi, OKAMURA Kazunori, KURIMOTO Keiji, ISOSHIMA Osamu, NAORA Yuka, KUMAZAWA Hiroshi, SUGIYAMA Masaaki, ANADA Takashi, SHIMIZU Hideki, NAKAMURA Tetsuya, KOBAYASHI Yoshitomo, KOBAYASHI Mitsuharu, TAKASHIBA Shogo, MIZUSHIMA Yumi, MITSUDA Yuka, YOKOYAMA Masayuki, KURIHARA Hidemi, KINOSHITA Masahiko, NOMURA Yoshio, MURAYAMA Yoji, OHTA Hiroyuki, KATO Keijiro

    Journal of the Japanese Association of Periodontology   29 ( 2 )   492 - 505   1987.6

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    Early-onset periodontitis has been implicated from the perspective of a host-parasite interaction. This case report describes microbiological examinations and the assessment of host defence function which were performed on a mother and daughter both of whom had early-onset periodontitis. The mother's diagnosis was rapidly progressive periodontitis. She had severe gingival inflammation and progressive bone destraction. The daughter's diagnosis was localized juvenile periodontitis. She had little gingival inflammation, but presented with progressive bone resorption. Microbiological examinations revealed an elevated proportion of rods and spirochetes from the mother's affected sites. Fewer spirochetes were found in the daughter's affected sites. Fusobacterium sp. were the predominant microorganisms in the plaque of both the mother and the daughter. Actinobacillus actinomycetemcomitans was not detected in the subgingival plaque of either the mother or the daughter. Humoral immune responces both in mother and daughter were much higher to F. nucleatum B. gingival, and A. actinomycetemcomitans than any other periodontally related microorganisms examined. Peripheral neutrophil functions were also studied. These studies demonstrated that the mother had a depressive neutrophil phagocytosis. The neutrophil studies performed for the daughter revealed a depressed function not only in neutrophil phagocytosis but also in neutrophil chemotaxis. From the perspective of host-parasite interaction, we propose that the disease status of the mother and the daughter are very similar. We believe the disease process in both the mother and the daughter strongly suggests an identical mechanism.

    DOI: 10.2329/perio.29.492

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    Other Link: http://search.jamas.or.jp/link/ui/1988053904

  • Serum Antibodies of Periodontaly Related Microorganisms : Changes of the IgG Antibodies Following Periodontal Treatment

    OKAMURA Kazunori, NAGAI Atsushi, KUMAZAWA Hiroshi, SUGIYAMA Masaaki, MIZUSHIMA Yumi, MITSUDA Yuka, TAKASHIBA Shogo, KURIHARA Hidemi, NOMURA Yoshio, MURAYAMA Yoji

    Journal of the Japanese Association of Periodontology   29 ( 1 )   146 - 154   1987.3

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    Several studies in serum antibodies of putative periodontopathic microorganisms have reported a correlation between specific antibacterial titers and the various forms of periodontal disease. In this report, effect of periodontal treatment on the levels of the IgG antibodies to Actinobacillus actinomycetemcomitans (Aa), Bacteroides gingivalis (Bg) and Capnocytophaga ochracea (Co) was evaluated. Sera were obtained from patients with periodontal diseases following periodontal treatment. The serum IgG antibody titers were assessed with an enzyme-linked immunosorbent assay (ELlSA). The antibody levels were compared before and after treatment. The post-treatment levels of the IgG antibodies to Aa, Bg and Co decreased significantly from the pre-treatment levels. The subjects were devided into two groups, a moderately improved group and a completely improved group. Decreases in the antibody levels were consistently found in the later group and not in the former group. In the completely improved group 20 of 23 patients (81%) ; 21 of 26 (87%); and 13 of 13 patients (100%) had decreased antibody levels to Aa, Bg and Co, respectively. A significantly decreased antibody level was defined as more than 20 per cent levels below the corresponding pre-treatment level. The IgG immune response differed according to the lapse of time after surgical treatments including scaling, root planing and peridontal surgery. The IgG antibody levels to Co decreased significantly in the early stages (within 30 days) after surgical treatment, in contrast those with Aa and Bg increased a little with no significant differences in the early stages. However, 30 days following after surgical treatment, those with Aa and Bg also decreased significantly. Surgical treatment is considered to boost the humoral immune response to the microorganisms. Generally, the IgG response elevated for 30 days or more after antigen exposure with the booster.

    DOI: 10.2329/perio.29.146

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    Other Link: http://search.jamas.or.jp/link/ui/1988088820

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  • 歯周病患者における抗菌薬適正使用のガイドライン2020

    山崎 和久, 五味 一博, 中川 種昭, 小松澤 均, 河口 浩之, 北村 正博, 栗原 英見, 齋藤 淳, 髙柴 正悟, 内藤 徹, 沼部 幸博, 廣藤 卓雄, 三辺 正人, 両⻆ 俊哉, 山本 松男, 吉成 伸夫( Role: Joint author)

    日本歯周病学会  2020.12 

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  • 歯周病と全身の健康

    (NPO) 日本歯周病学会  2016 

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  • 最新歯科衛生士教本 歯周病学 第2版

    医歯薬出版  2015 

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  • 歯周病の検査キット,薬 '15/'16 歯科 疾患名から治療薬と処方例がすぐわかる本.第1版

    クインテッセンス出版  2014 

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  • 歯周病と7つの病気,8つのNEWS

    吉江 弘正, 高柴 正悟, 岩本 義博

    永末書店,京都  2007  ( ISBN:9784816011825

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    Total pages:v, 193p, 図版[2]p   Language:Japanese

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  • 腸内細菌・口腔細菌と全身疾患

    シーエムシー出版  2015 

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  • 感染していることがわかった患者への対応(第2部歯科医院に勧める効果的な「院内感染」対策),患者が求める「医療安全」「院内感染」対策

    ヒョーロン・パブリッシャーズ  2014 

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  • 臨床歯周病学 第2版

    医歯薬出版株式会社  2013 

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  • Kommunikation Der Zellen Illustrierte Beitrage aus der Zahnmedizinischen Forschung und Praxis

    Quintessenz Verlag  2013 

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  • イラストで語る歯科医学最前線

    クインテッセンス出版株式会社  2013 

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  • At The Forefront Illustrated Topics in Dental Research and Clinical Practice

    Quintessence Publishing Co, Inc  2012  ( ISBN:9780867155150

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  • 歯科衛生士のための歯周治療ガイドブック

    医歯薬出版株式界者  2009 

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  • 歯科医師・歯科衛生士のための唾液検査ハンドブック

    ヒョーロン・パブリッシャーズ,東京  2008 

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  • 別冊the Quintessence YEAR BOOK 2008 現代の治療指針 歯周治療と全治療分野編

    クインテッセンス出版,東京  2008 

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  • Preventive Periodontology

    医歯薬出版,東京  2007 

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  • 臨床歯周病学

    医歯薬出版,東京  2007 

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  • 歯周病の遺伝子治療 : 局所的遺伝子導入による生体反応の制御

    高柴, 正悟, 窪木, 拓男

    高柴正悟  2006 

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  • 最新歯科衛生士教本 歯周疾患

    医歯薬出版,東京  2006 

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  • 象牙質特異遺伝子を局所に導入することによって歯質保全を図る研究

    高柴, 正悟

    高柴正悟  2002 

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  • 単球系細胞が産生するTNF-αの新規転写因子を制御することによる歯周炎治療

    高柴 正悟

    高柴正悟  2002 

  • ペリオドンタルメディスン

    医歯薬出版株式会社  2001 

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  • 先端医療シリーズ・歯科医学2 歯周病 新しい治療を求めて

    寺田国際事務所/先端医療技術研究所  2000 

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  • 歯周病の病因 歯周病の遺伝的素因(単著)

    先端医療シリーズ・歯科医学2 歯周病 新しい治療を求めて 寺田国際事務所/先端医療技術研究所  2000 

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  • 歯周病学最前線

    日本歯科評論社  2000 

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  • Progress of Periodontal Research and Practice in Asian Pacific Countries

    Asian Pacific Society of Periodontology  2000 

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  • Concepts for the biological treatment of periodontal diseases(jointly worked)

    Progress of Periodontal Research and Practice in Asian Pacific Countries  2000 

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  • Concepts for the biological treatment of periodontal diseases(jointly worked)

    Progress of Periodontal Research and Practice in Asian Pacific Countries  2000 

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  • 組織再生性歯周療法 炎症をどうコントロールするか(単著)

    歯周病学最前線 日本歯科評論  2000 

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  • 第2編 免疫・遺伝子診断のためのリサーチプロセス,4.白血球からみた感受性診断(共著)

    歯周病診断のストラテジー医歯薬出版  1999 

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  • 歯周疾患:晩期発症型歯周炎,早期発症型歯周炎,白血病の歯周炎,妊娠時の歯周炎,糖尿病の歯周炎,口呼吸による歯周炎,薬剤による歯周炎,剥離性歯内炎(共著)

    カラーでみる口腔粘膜疾患の診かた 南江堂  1999 

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  • 歯周疾患と遺伝的背景(共著)

    歯周病学 永末書店  1996 

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  • Assessment of host defense risk factors for periodontal disease : a case of family members with juvenile periodontitis(jointly worked)

    Risk Factors in Asian Pacific Population  1996 

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  • Assessment of host defense risk factors for periodontal disease : a case of family members with juvenile periodontitis(jointly worked)

    Risk Factors in Asian Pacific Population  1996 

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  • Leukocyte adhesion molecules CD11/CD18 and their role in periodontal diseases(jointly worked)

    Molecular Pathogenesis of Periodontal Disease ASM Press  1994 

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  • Leukocyte adhesion molecules CD11/CD18 and their role in periodontal diseases(jointly worked)

    Molecular Pathogenesis of Periodontal Disease ASM Press  1994 

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  • Polymorphism of compromised hosts in periodontitis patients(jointly worked)

    Recent advances in clinical periodontology Elsevier Science Publisher B.V.  1988 

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  • Polymorphism of compromised hosts in periodontitis patients(jointly worked)

    Recent advances in clinical periodontology Elsevier Science Publisher B.V.  1988 

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MISC

  • 歯周感染が子宮組織に及ぼす影響のマウス絹糸結紮歯周炎モデルにおける免疫学的検討

    永田 千晶, 大森 一弘, 井手口 英隆, 佐光 秀文, 坂井田 京佑, 徳善 真砂子, 平井 公人, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   63 ( 秋季特別 )   118 - 118   2021.10

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  • 脳卒中急性期におけるOHATを活用した口腔管理体制の効果

    中濱 加奈子, 松永 一幸, 坪井 綾香, 吉田 泰子, 中村 和希, 佐能 紗希, 猪原 健, 高柴 正悟, 郡山 達男

    日本口腔検査学会総会・学術大会プログラム・抄録集   14回   45 - 45   2021.8

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  • 短鎖脂肪酸は歯周炎症のバイオマーカーになり得るか

    児玉 加奈子, 畑中 加珠, 小西 健司, 白波瀬 泰史, 河野 麻理, 吉田 敏之, 戸谷 直樹, 酒瀬川 信一, 落合 邦康, 山本 直史, 高柴 正悟

    日本口腔検査学会総会・学術大会プログラム・抄録集   14回   50 - 50   2021.8

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  • 歯科治療に起因する感染性心内膜炎の発症予防を目指す岡山大学病院成人先天性心疾患センターの取り組み

    久保田 萌可, 大森 一弘, 杜 徳尚, 佐光 秀文, 井手口 英隆, 岡本 憲太郎, 山本 直史, 赤木 禎治, 笠原 真悟, 伊藤 浩, 高柴 正悟

    日本未病学会学術総会抄録集   29回   75 - 75   2022.10

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  • 歯科から未病化への展望 未病化への歯科貢献を考える

    高柴 正悟

    日本未病学会学術総会抄録集   29回   61 - 61   2022.10

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  • 関節リウマチ患者の治療反応性に対する歯周病感染の影響と新たな医科歯科連携の提案

    釜田 英幸, 畑中 加珠, 小山 芳伸, 山本 直史, 高柴 正悟

    日本未病学会学術総会抄録集   29回   74 - 74   2022.10

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  • 【歯周病が及ぼす全身疾患への影響】歯周病の要因および全身疾患との関連 歯周病と肺炎

    高柴 正悟

    診断と治療   110 ( 9 )   1159 - 1163   2022.9

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    <Headline>1 高齢社会になった日本において肺炎は死因の上位に位置するが、その多くに細菌を含む唾液の不顕性誤嚥が関連する誤嚥性肺炎が関与している。2 80歳で20本以上の歯をもつ8020達成者が50%を超える時代となり、歯のある高齢者の歯周病罹患リスクは高く、加齢によるオーラルフレイルと相まって、口腔細菌の質と量は変化する。3 さらに、中高年期以降には慢性閉塞性肺疾患(COPD)の罹患者が増加していることから、唾液の誤嚥はCOPDの悪化にも関連すると考えられる。4 SARS-CoV-2ウイルスの侵入門戸であるアンジオテンシン転換酵素2(ACE2)が歯肉を始めとする口腔組織に高発現しており、歯周病などの炎症によって発現量が増加することも、新型コロナウイルス感染症(COVID-19)の肺炎悪化に関連する可能性もある。(著者抄録)

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  • 低侵襲性歯周組織再生療法を行った侵襲性歯周炎症例

    松本 俊樹, 井手口 英隆, 吉田 陽子, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   64 ( 秋季特別 )   124 - 124   2022.8

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  • マウス絹糸結紮歯周炎モデルを用いた歯周感染が妊娠成績や子宮組織に及ぼす影響の検討

    永田 千晶, 大森 一弘, 井手口 英隆, 佐光 秀文, 坂井田 京佑, 大原 利章, 徳善 真砂子, 平井 公人, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   64 ( 秋季特別 )   124 - 124   2022.8

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  • 全身性疾患への影響を考慮した新たな歯周病重症度検査項目の策定 学会主導型多施設臨床研究

    松田 真司, 菅谷 勉, 加藤 幸紀, 根本 英二, 竹内 康雄, 喜田 大智, 沼部 幸博, 西田 哲也, 小方 頼昌, 申 基哲, 長野 孝俊, 両角 俊哉, 小松 康高, 出分 菜々衣, 神谷 洋介, 北村 正博, 田口 洋一郎, 高柴 正悟, 湯本 浩通, 山下 明子, 吉永 泰周, 吉村 篤利, 河口 浩之

    日本歯周病学会会誌   64 ( 秋季特別 )   112 - 112   2022.8

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  • コラーゲン結合型塩基性線維芽細胞成長因子は局所滞留性によって水平性骨欠損における歯周組織再生を促進する

    岡本 憲太郎, 伊東 孝, 中村 心, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   64 ( 秋季特別 )   123 - 123   2022.8

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  • HMGB1はマクロファージをM1タイプに極性化させて歯周炎の進行に影響を及ぼす

    平井 杏奈, 井手口 英隆, 山城 圭介, 青柳 浩明, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   64 ( 春季特別 )   114 - 114   2022.5

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  • 歯周病学の不易流行 歯周病の検査結果と治療経過を持ち歩く時代

    高柴 正悟

    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   156回   12 - 12   2022.5

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  • Resolvin D2は歯髄幹細胞の増殖を促進して直接覆髄の断髄面における硬組織形成を誘導する

    米田 光宏, 井手口 英隆, 中村 心, Arias Martinez Zulema Rosalia, 山本 直史, 高柴 正悟

    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   156回   26 - 26   2022.5

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  • 侵襲性歯周炎の血液診断マーカー候補となる細胞外小胞由来マイクロRNAとその炎症誘導機構の探索

    森 彩乃, 山本 直史, 井手口 英隆, 河村 麻理, 河本 美奈, 伊東 昌洋, 小野 喜章, 中山 真彰, 江口 傑徳, 大野 充昭, 大森 一弘, 高柴 正悟

    日本歯周病学会会誌   64 ( 春季特別 )   114 - 114   2022.5

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  • 血清の細菌抗体価検査を指標に治療を進めた咬合性外傷を伴う慢性歯周炎症例での15年間の治療経過と感染管理

    畑中 加珠, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   64 ( 春季特別 )   149 - 149   2022.5

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  • 【歯周病-看過できない口腔感染症-】歯周病治療の考え方 全身性疾患を有する歯周病患者に対する医科歯科連携の重要性

    高柴 正悟

    Progress in Medicine   42 ( 4 )   389 - 393   2022.4

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  • 侵襲性歯周炎の血液診断マーカー候補となる細胞外小胞由来マイクロRNAとその炎症誘導機構の探索

    森彩乃, 山本直史, 井手口英隆, 河村麻理, 河本美奈, 伊東昌洋, 小野喜章, 中山真彰, 江口傑徳, 大野充昭, 大森一弘, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • Dental hygienists’ efforts to prevent the development of oral mucositis at the oncology center, Okayama University Hospital

    杉浦裕子, 大森一弘, 山本大介, 山本大介, 三浦留美, 曽我賢彦, 山本直史, 高柴正悟

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   157th   2022

  • コラーゲン結合型塩基性線維芽細胞成長因子は局所滞留性によって水平性骨欠損における歯周組織再生を促進する

    岡本憲太郎, 伊東孝, 中村心, 大森一弘, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • Thickening of uterine tissue induced by infection and inflammation of periodontal tissue and its effect on pregnancy

    永田千晶, 大森一弘, 井手口英隆, 佐光秀文, 坂井田京佑, 久保田萌可, 大原利章, 萬代大樹, 平井公人, 池田淳史, 山本直史, 高柴正悟

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   157th   2022

  • A case of endodontic-periodontal lesion of endodontic origin characterized by root bifurcation lesion: importance for pathophysiological diagnosis in a full-mouth unit

    佐光秀文, 大森一弘, 井手口英隆, 山本直史, 高柴正悟

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   157th   2022

  • 低侵襲性歯周組織再生療法を行った侵襲性歯周炎症例

    松本俊樹, 井手口英隆, 吉田陽子, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • 血清の細菌抗体価検査を指標に治療を進めた咬合性外傷を伴う慢性歯周炎症例での15年間の治療経過と感染管理

    畑中加珠, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • HMGB1はマクロファージをM1タイプに極性化させて歯周炎の進行に影響を及ぼす

    平井杏奈, 井手口英隆, 山城圭介, 青柳浩明, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • マウス絹糸結紮歯周炎モデルを用いた歯周感染が妊娠成績や子宮組織に及ぼす影響の検討

    永田千晶, 大森一弘, 井手口英隆, 佐光秀文, 坂井田京佑, 大原利章, 徳善真砂子, 平井公人, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   64   2022

  • 歯科ユニット給水管路(DUWL)内汚染の実際と電解機能水の効果

    上田 彩華, 伊東 有希[信田], 大森 一弘, 伊東 孝, 大久保 圭祐, 平井 公人, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   40 ( 2 )   32 - 33   2021.12

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  • フッ化ナトリウムによるCCNファミリー遺伝子制御を介した歯肉線維化抑制作用の検討

    水川 朋美, 西田 崇, 明石 翔, 大杉 綾花, 大森 一弘, 中山 真彰, 高柴 正悟, 上岡 寛, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   40 ( 2 )   34 - 35   2021.12

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  • 歯内治療が原因で菌血症となった単心室症患者の症例報告とその対応策の提案

    児玉 加奈子, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 松本 俊樹, 大森 一弘, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   40 ( 2 )   35 - 35   2021.12

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  • 大豆発酵食品テンペによる口腔感染症の制御

    伊東 昌洋, 伊東 孝, 中村 心, 青木 秀之, 西岡 功志, 塩川 つぐみ, 多田 宏子, 竹内 祐貴, 武安 伸幸, 山本 直史, 高柴 正悟

    日本未病学会学術総会抄録集   28回   119 - 119   2021.11

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  • 不妊治療中患者における歯周病原細菌の感染度調査 血清IgG抗体価検査を応用したパイロット研究

    永田 千晶, 大森 一弘, 佐光 秀文, 坂井田 京佑, 井手口 英隆, 池田 淳史, 徳善 真砂子, 平井 公人, 畑中 加珠, 山本 直史, 滝川 雅之, 三宅 貴仁, 高柴 正悟

    日本未病学会学術総会抄録集   28回   106 - 106   2021.11

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  • 歯科ユニット給水管路(DUWL)内汚染の実際と電解機能水の効果

    伊東 有希[信田], 大森 一弘, 伊東 孝, 大久保 圭祐, 平井 公人, 山本 直史, 高柴 正悟

    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   155回   131 - 131   2021.10

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  • RNAシャペロンであるHfqはAggregatibacter actinomycetemcomitansの病原因子を制御する

    尾内 千晃, 平井 公人, 池田 淳史, 伊東 昌洋, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   63 ( 秋季特別 )   119 - 119   2021.10

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  • 二次性咬合性外傷を伴う広汎型慢性歯周炎患者に対する10年経過症例の成功要因

    岩本 義博, 塩田 康祥, 湊 ゆかり, 吉田 充哉, 高柴 正悟

    日本歯周病学会会誌   63 ( 秋季特別 )   151 - 151   2021.10

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  • 歯内治療が原因で菌血症となった単心室症患者の症例報告とその対応策の提案

    児玉 加奈子, 井手口 英隆, 岡本 憲太郎, 佐光 秀文, 松本 俊樹, 大森 一弘, 山本 直史, 高柴 正悟

    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   155回   112 - 112   2021.10

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  • Notchシグナル伝達経路を介した破骨細胞分化のメカニズム

    本行 令奈, 池田 淳史, 山本 直史, 高柴 正悟

    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   155回   35 - 35   2021.10

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  • 徹底した感染源除去が奏功した広汎型侵襲性歯周炎患者の15年臨床経過

    山本 直史, 小柳津 功介, 高柴 正悟

    日本歯周病学会会誌   63 ( 秋季特別 )   155 - 155   2021.10

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  • 歯周病のポケット検査における代表歯・部位の選定

    両角 俊哉, 高柴 正悟, 三邉 正人, 野村 義明, 福田 光男, 花田 信弘, 角田 衣理加, 小林 宏明, 中村 利明, 中山 洋平, 西村 英紀, 野口 和行, 沼部 幸博, 小方 頼昌, 齋藤 淳, 佐藤 聡, 関野 愉, 菅野 直之, 菅谷 勉, 鈴木 史彦, 多部田 康一, 高橋 慶壮, 高井 英樹, 梅田 誠, 吉村 篤利, 吉成 伸夫, 中川 種昭

    日本口腔検査学会総会・学術大会プログラム・抄録集   14回   70 - 71   2021.8

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  • 人獣共通感染症の制御に向けたphytochemicalを利用したアプローチ

    松本 俊樹, 伊東 昌洋, 徳善 真砂子, 青木 秀之, 西岡 功志, 山本 直史, 高柴 正悟

    日本口腔検査学会総会・学術大会プログラム・抄録集   14回   67 - 67   2021.8

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  • 骨吸収抑制薬関連顎骨壊死(ARONJ)の診断におけるMRIの有用性

    井上 裕貴, 古川 康平, 三浦 晃子, 岩田 玲子, 山内 晴美, 川野 瞳, 門田 伸也, 濱本 康, 神崎 博充, 高柴 正悟

    日本口腔検査学会総会・学術大会プログラム・抄録集   14回   48 - 48   2021.8

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  • ω-3脂肪酸誘導体の抗炎症作用による歯髄保存の試み

    米田 光宏, Zulema Rosalia Arias Martinez, 中村 心, 岡本 憲太郎, 伊東 昌洋, 田村 和也, 井手口 英隆, 大森 一弘, 山城 圭介, 山本 直史, 高柴 正悟

    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   154回   140 - 140   2021.5

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  • X連鎖性低リン血症性くる病を起因とした多発根尖性歯周炎に対し歯内療法を行った症例の病態考察

    佐光 秀文, 大森 一弘, 坂井田 京佑, 亀井 千晶, 小林 寛也, 井手口 英隆, 山本 直史, 高柴 正悟

    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   154回   126 - 126   2021.5

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  • 大豆発酵食品テンペに含まれる抗菌性物質の単離と同定

    伊東 昌洋, 伊東 孝, 中村 心, 青木 秀之, 西岡 功志, 塩川 つぐみ, 多田 宏子, 竹内 祐貴, 武安 伸幸, 山本 直史, 高柴 正悟

    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   154回   159 - 159   2021.5

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  • HMGB1はM1マクロファージの分化を制御して歯周炎の進行に影響を及ぼす

    平井 杏奈, 井手口 英隆, 山城 圭介, Yao Zhang, 青柳 浩明, 山本 直史, 高柴 正悟

    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   154回   155 - 155   2021.5

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  • 歯周病評価における最適検査部位の選定 項目反応理論Graded response modelの応用

    両角 俊哉, 野村 義明, 福田 光男, 花田 信弘, 角田 衣理加, 小林 宏明, 三邉 正人, 中村 利明, 中山 洋平, 西村 英紀, 野口 和行, 沼部 幸博, 小方 頼昌, 齋藤 淳, 佐藤 聡, 関野 愉, 菅野 直之, 菅谷 勉, 鈴木 史彦, 多部田 康一, 高橋 慶壮, 高井 英樹, 高柴 正悟, 梅田 誠, 吉江 弘正, 吉村 篤利, 吉成 伸夫, 中川 種昭

    日本歯周病学会会誌   63 ( 春季特別 )   106 - 106   2021.5

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  • 不妊治療中患者に対する血清IgG抗体価検査を用いた歯周病原細菌の感染度調査

    亀井 千晶, 大森 一弘, 佐光 秀文, 坂井田 京佑, 徳善 真砂子, 平井 公人, 小林 寛也, 山本 直史, 滝川 雅之, 三宅 貴仁, 高柴 正悟

    日本歯周病学会会誌   63 ( 春季特別 )   102 - 102   2021.5

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  • 歯科保存治療での「保存の可否」とは? 生命を紡ぐ

    高柴 正悟

    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   154回   40 - 40   2021.5

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  • Aggregatibacter actinomycetemcomitansに対し高い血清IgG抗体価反応を示す歯周炎患者の治療経過と病態考察

    岡本 憲太郎, 高知 信介, 小林 寛也, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   63 ( 春季特別 )   120 - 120   2021.5

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  • Aggregatibacter actinomycetemcomitansに対し高い血清IgG抗体価反応を示す歯周炎患者の治療経過と病態考察

    岡本 憲太郎, 高知 信介, 小林 寛也, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   63 ( 春季特別 )   120 - 120   2021.5

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  • ω-3脂肪酸誘導体の抗炎症作用による歯髄保存の試み

    米田 光宏, Zulema Rosalia Arias Martinez, 中村 心, 岡本 憲太郎, 伊東 昌洋, 田村 和也, 井手口 英隆, 大森 一弘, 山城 圭介, 山本 直史, 高柴 正悟

    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   154回   140 - 140   2021.5

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  • X連鎖性低リン血症性くる病を起因とした多発根尖性歯周炎に対し歯内療法を行った症例の病態考察

    佐光 秀文, 大森 一弘, 坂井田 京佑, 亀井 千晶, 小林 寛也, 井手口 英隆, 山本 直史, 高柴 正悟

    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   154回   126 - 126   2021.5

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  • 歯科保存治療での「保存の可否」とは? 生命を紡ぐ

    高柴 正悟

    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   154回   40 - 40   2021.5

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  • 大豆発酵食品テンペに含まれる抗菌性物質の単離と同定

    伊東 昌洋, 伊東 孝, 中村 心, 青木 秀之, 西岡 功志, 塩川 つぐみ, 多田 宏子, 竹内 祐貴, 武安 伸幸, 山本 直史, 高柴 正悟

    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   154回   159 - 159   2021.5

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  • HMGB1はM1マクロファージの分化を制御して歯周炎の進行に影響を及ぼす

    平井 杏奈, 井手口 英隆, 山城 圭介, Yao Zhang, 青柳 浩明, 山本 直史, 高柴 正悟

    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   154回   155 - 155   2021.5

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  • 【産婦人科医も知っておきたい歯科の知識】歯周病と不妊

    大森 一弘, 高柴 正悟, 三宅 貴仁

    産科と婦人科   88 ( 4 )   465 - 469   2021.4

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    歯周病は、Porphyromonas gingivalisに代表される歯周病原細菌が歯周組織に感染して発症する口腔感染症である。近年、歯周病原細菌の感染、そして、感染によって惹起された歯周炎症が不妊環境の構築に関与する可能性が示唆されはじめている。本稿では、歯周病と不妊の関連について文献的に考察するとともに、不妊治療中の重度歯周病患者に専門的治療を行うことによって自然妊娠・正常出産に至った実症例を提示しながら、その関連性を考察する。(著者抄録)

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  • コラーゲン結合型塩基性線維芽細胞増殖因子を用いた水平性骨吸収に対する歯周組織再生療法の開発

    中村 心, 伊東 孝, 岡本 憲太郎, 美間 健彦, 内田 健太郎, 山本 直史, 松下 治, 高柴 正悟

    日本歯科医学会誌   40   78 - 78   2021.3

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  • 臨床推論の教育をどうするか 病態の理解は検査と臨床推論から

    高柴 正悟

    日本口腔診断学会雑誌   34 ( 1 )   52 - 52   2021.2

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  • 歯内療法の薬物的な新規治療

    高柴 正悟

    日本歯内療法学会雑誌   42 ( 1 )   1 - 4   2021.1

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    炎症の場においては、組織の炎症を調整するメディエーターが急性期に作用して炎症を解消し、炎症性に破壊された組織を結果的に再生へ向かわせる。この作用を活用した炎症性疾患治療の、歯内療法への応用を紹介した。歯髄や根尖歯周組織の炎症を調節し、組織の修復・再生に向かわせる生体反応調節性の歯内療法薬剤の研究開発が期待されている。

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  • 【ペリオと○○-最新歯周治療トピックス集-】(Topic 5)ペリオとPISA 歯周組織の炎症面積で歯周病の重症度を表現しよう!

    高柴 正悟

    デンタルハイジーン   41 ( 1 )   40 - 42   2021.1

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  • RNAシャペロンであるHfqはAggregatibacter actinomycetemcomitansの病原因子を制御する

    尾内千晃, 平井公人, 池田淳史, 伊東昌洋, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   63   2021

  • 歯周感染が子宮組織に及ぼす影響のマウス絹糸結紮歯周炎モデルにおける免疫学的検討

    永田千晶, 大森一弘, 井手口英隆, 佐光秀文, 坂井田京佑, 徳善真砂子, 平井公人, 山本直史, 高柴正悟

    日本歯周病学会会誌(Web)   63   2021

  • 徹底した感染源除去が奏功した広汎型侵襲性歯周炎患者の15年臨床経過

    山本直史, 小柳津功介, 高柴正悟

    日本歯周病学会会誌(Web)   63   2021

  • 臨床推論の教育をどうするか 病態の理解は検査と臨床推論から

    高柴 正悟

    日本口腔内科学会雑誌   26 ( 2 )   100 - 100   2020.12

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  • 侵襲性歯周炎の血液診断バイオマーカーとしての細胞外小胞由来マイクロRNAの探索

    河本 美奈, 山本 直史, 河村 麻理, 森 彩乃, 山城 圭介, 大森 一弘, 小野 喜章, 江口 傑徳, 十川 千春, 高柴 正悟

    岡山歯学会雑誌   39 ( 2 )   35 - 36   2020.12

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  • 子宮内膜症の治療と妊娠を契機に進行したと疑われる慢性歯周炎患者の病態考察と治療経過

    坂井田 京佑, 大森 一弘, 小林 寛也, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   39 ( 2 )   36 - 37   2020.12

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  • 真菌代謝産物(+)-terreinがマウス骨粗鬆症モデルにおける骨代謝に及ぼす影響

    坂井田 京佑, 大森 一弘, 中川 沙紀, 佐光 秀文, 亀井 千晶, 山本 総司, 小林 寛也, 山城 圭介, 山本 直史, 高柴 正悟

    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   153回   36 - 36   2020.11

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  • 急性期脳卒中患者における喀痰内の多剤耐性菌検出とその関連因子(横断研究)

    井上 裕貴, 松永 一幸, 山城 圭介, 高柴 正悟

    日本未病学会学術総会抄録集   27回   107 - 107   2020.10

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  • 歯の病的移動と歯周-歯内病変を併発した侵襲性歯周炎患者に対する歯周組織再生療法

    本行 令奈, 井手口 英隆, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 秋季特別 )   142 - 142   2020.10

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  • 24年間の治療効果に関係なく高い抗P.gingivalis IgG抗体価を示す限局性侵襲性歯周炎患者

    峯柴 淳二, 峯柴 史, 岩本 義博, 高柴 正悟

    日本歯周病学会会誌   62 ( 秋季特別 )   133 - 133   2020.10

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  • 次の時代を見据えた戦略的未病対策とは 歯科疾患の未病対策は全身の未病対策に繋がる

    高柴 正悟

    日本未病学会学術総会抄録集   27回   71 - 71   2020.10

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  • ハンチントン舞踏病の広汎型慢性歯周炎患者への歯周病治療で感じた歯科衛生士の役割

    佐藤 由実, 伊藤 実有, 北村 彰子, よし田 亜紀, 苅田 奈生子, 磯島 大地, 伊東 昌洋, 長島 義之, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 秋季特別 )   152 - 152   2020.10

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  • 歯周組織の炎症と不妊の関連性を示唆する、ある侵襲性歯周炎患者の病態生理

    大森 一弘, 河野 隆幸, 小林 寛也, 新井 英雄, 山本 直史, 高柴 正悟

    日本歯科保存学雑誌   63 ( 5 )   451 - 460   2020.10

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    緒言:歯周病原細菌の感染と歯周組織の炎症が,妊娠に影響を与える可能性が報告されている.今回,不妊治療の経過が思わしくない侵襲性歯周炎患者に感染源除去の観点から専門的歯周治療を行い,自然妊娠から正常出産にいたった症例の経過をふまえ病態を考察する.症例:33歳,女性,既婚(不妊治療中).2016年9月,26の動揺および同部の自発痛を自覚し,かかりつけ歯科医院を受診した.同院でエックス線検査を受けて,重度の歯槽骨吸収があると説明された.早期の専門的歯周治療を勧められ,当科を紹介された.既往歴の特記事項はなく,不妊検査においても患者本人および夫ともに異常所見はなかった.歯周組織検査において,probing pocket depthが4mm以上の部位の割合は49.5%,bleeding on probingは47.9%,plaque control recordは3.1%,歯周炎症表面積(PISA)は2,392mm2であった.エックス線検査所見では,主訴部の26部を中心に根尖に及ぶ骨吸収像が多数存在した.歯周病原細菌に対する血清抗体価検査および歯周ポケット内細菌DNA検査ともに,Porphyromonas gingivalisの感染が強く疑われた.診断は広汎型侵襲性歯周炎(ステージIV,グレードC),二次性咬合性外傷とした.治療方針として,患者の妊娠希望に配慮して,できるかぎり早期(1年以内)の歯周環境の改善を目指すこととした.また,歯周外科治療が終了するまでの不妊治療を含めた妊娠活動を控える必要性について説明し,同意を得た.治療計画は,(1)歯周基本治療(患者教育,抜歯,局所抗菌療法を併用したスケーリング・ルートプレーニング,暫間固定),(2)歯周組織再生療法,(3)口腔機能回復治療,(4)歯周病安定期治療(SPT)とした.治療経過として,歯周治療に対する宿主反応性は非常に良く,炎症改善と歯槽骨の再生を確認した(歯周外科治療後PISA:43mm2).口腔機能回復治療中に自然妊娠し,35歳時に男児を正常出産(経腟分娩,3,240g,出産週数:38週+5日)した.考察および結論:重度のP. gingivalis感染および歯周炎症を伴う侵襲性歯周炎の罹患が,妊娠成立に影響を及ぼす可能性が示唆された.本症例のように不妊治療の経過が思わしくない場合には,歯周組織を含めた口腔状態を一度精査することが望まれる.(著者抄録)

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  • 急性期脳卒中患者における喀痰内の多剤耐性菌検出とその関連因子(横断研究)

    井上 裕貴, 松永 一幸, 坪井 綾香, 山城 圭介, 高柴 正悟

    日本歯周病学会会誌   62 ( 秋季特別 )   125 - 125   2020.10

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  • High Mobility Group Box 1(HMGB1)はマクロファージからのCCL2分泌を制御して抜歯窩の歯周組織再生を促進する

    井手口 英隆, 平井 杏奈, 山城 圭介, 京嶌 里沙, 青柳 浩明, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 秋季特別 )   121 - 121   2020.10

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  • 新しい日本での歯周病治療と歯周病専門医の展開

    高柴 正悟

    日本歯周病学会会誌   62 ( 3 )   129 - 135   2020.9

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    超高齢社会の日本において医療界、特に歯科医療界がどこに向かうのか考察した。大学を含む病院が主な勤務先である医師とは異なり、歯科医師はほとんどが歯科診療所に勤務している。また、厚労省の統計によると歯科医師は医師よりも平均年齢が7歳若く、これは高齢者の割合が増加している患者への対応方法に若干の違いをもたらしている可能性がある。一方で医師と歯科医師の分布の地域差が顕著であり、来たるべき歯科医師の高齢化についても配慮が必要となる。こうした社会の変化の中で、日本歯周病学会の歯周病専門医は厚生労働省の「医療に関する広告が可能となった医師等の専門性に関する資格名」として周知されている。今後は、(一社)日本歯科専門医機構の承認も得ることには違いない。また、高度で広範囲な歯周病専門医による治療を日本国内の各地に均平化することも必要である。

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  • インテグリンα3の選択的阻害による微小環境の構築と歯槽骨再生

    森 彩乃, 山本 直史, 河村 麻理, 井手口 英隆, 青柳 浩明, 中村 心, 岡本 憲太郎, 平井 杏奈, 山城 圭介, 大森 一弘, 高柴 正悟

    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   142 - 142   2020.6

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  • High Mobility Group Box 1が抜歯窩治癒過程の間葉系幹細胞の遊走に及ぼす影響

    京嶌 里紗, 井手口 英隆, 山城 圭介, 平井 杏奈, 青柳 浩明, 山本 直史, 高柴 正悟

    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   141 - 141   2020.6

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  • 血糖管理不良の2型糖尿病に罹患する重度慢性歯周炎患者への歯周治療

    山城 圭介, 新井 英雄, アリアス・スレマ, 高柴 正悟

    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   55 - 55   2020.6

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  • 歯髄壊死した根未完成下顎第二小臼歯に対してrevascularizationを行った症例

    佐光 秀文, 高柴 正悟

    日本歯内療法学会学術大会プログラム・抄録集   41回   91 - 91   2020.6

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  • 歯周病重症度マーカーとしての洗口液・唾液・歯肉溝滲出液中の短鎖脂肪酸

    畑中 加珠, 川瀬 貴博, 白波瀬 泰史, 河野 麻理, 吉田 敏之, 塚原 隆充, 落合 邦康, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 春季特別 )   145 - 145   2020.5

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  • 真菌二次代謝産物(+)-terreinはTNF-αの発現を抑制し歯周炎マウスモデルにおける歯槽骨吸収を抑制する

    佐光 秀文, 大森 一弘, 中川 沙紀, 亀井 千晶, 坂井田 京佑, 山本 総司, 井手口 英隆, 小林 寛也, 山城 圭介, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 春季特別 )   141 - 141   2020.5

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  • 歯周組織再生療法の違いが歯肉縁下細菌叢に及ぼす影響 侵襲性歯周炎患者の一症例

    大森 一弘, 河野 隆幸, 新井 英雄, 小林 寛也, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   62 ( 春季特別 )   165 - 165   2020.5

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  • 急性期脳卒中患者における入院時評価項目と喀痰内の薬剤耐性菌検出状況に関する調査

    井上 裕貴, 松永 一幸, 山城 圭介, 高柴 正悟

    日本口腔診断学会雑誌   33 ( 1 )   119 - 119   2020.2

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  • 歯科用接着性レジン系セメントを用いた補綴物装着によるアレルギー発症症例と検査の考察

    山城 圭介, 北川 雅恵, 岡 広子, 高柴 正悟

    日本口腔診断学会雑誌   33 ( 1 )   88 - 88   2020.2

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  • 細菌性コラゲナーゼのコラーゲン・アンカーの構造活性相関と歯周病治療への応用

    松下 治, 美間 健彦, 後藤 和義, 山本 由弥子, Caviness Perry, Sakon Joshua, 内田 健太郎, 中村 心, 岡本 健太郎, 高柴 正悟

    日本細菌学雑誌   75 ( 1 )   138 - 138   2020.1

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  • Endodontic Management of a Mandible Premolar with 3 root canals-A Case Report-

    ROSALIA Arias Martinez Zulema, YAMASHIRO Keisuke, SHINODA-ITO Yuki, YAMAMOTO Tadashi, TAKASHIBA Shogo

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   152nd   2020

  • 真菌二次代謝産物terreinはマウス歯周病モデルにおける歯槽骨吸収を抑制する

    佐光 秀文, 大森 一弘, 中川 沙紀, 坂井田 京佑, 山本 総司, 青柳 浩明, 小林 寛也, 大野 充昭, 平井 公人, 山城 圭介, 山本 直史, 高柴 正悟

    有病者歯科医療   28 ( 6 )   430 - 431   2019.12

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  • 多施設後ろ向き観察研究による臨床指標としての歯周炎症表面積の基準値

    井上 裕貴, 畑中 加珠, 山本 直史, 平田 貴久, 三辺 正人, 山本 龍生, 内藤 徹, 山本 松男, 佐藤 秀一, 石幡 浩志, 稲垣 幸司, 三谷 章雄, 中島 啓介, 漆原 譲治, 高柴 正悟

    日本歯周病学会会誌   61 ( 4 )   159 - 167   2019.12

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    歯周炎症表面積(periodontal inflamed surface area:PISA)は,歯周組織の炎症部の面積を表す新たな歯周病の臨床指標である。従来伝わりづらかった歯周病の炎症程度を歯科以外の医療従事者が理解する上で,有用な指標であると考えられる。しかし,歯周病の程度や治療によるPISAの基準は未だ不明である。そこで,本研究は,日本歯周病学会が設ける歯周病専門医・認定医の電子申請書類のデータから各治療フェーズにおけるPISAの値を調べ,歯周病治療に伴う炎症度の基準値を提案することを目的とした。8施設で取得した113症例を用いて,Nesseらの方法によって歯周ポケット深さとプロービング時の出血からPISAを算出した。その結果,PISAの中央値は,初診時1,271.4mm2,歯周基本治療終了時211.8mm2,SPT移行時52.1mm2,そして最新SPT時30.0mm2であった。また,PISAはBOPと高い相関を示し(p<0.001),BOPよりも鋭敏に治療効果を反映した。以上から,中等度以上の歯周炎においてPISAを用いると,初診時は表面積約1,500mm2の歯周組織の炎症がSPT時は100mm2未満(初診時の約7%)に減少することが明らかになった。今後,更なるデータの蓄積および詳細な分析を行いながらPISAの使用を普及させると,PISAは医科歯科連携の際に歯周病炎症を伝える指標になり得ると考える。(著者抄録)

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  • 歯周組織の炎症と不妊との関連性を示唆する侵襲性歯周炎症例の病態生理 岡山大学病院・侵襲性歯周炎センターでの取り組み

    亀井 千晶, 大森 一弘, 小林 寛也, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   38 ( 2 )   91 - 92   2019.12

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  • フッ素イオンによるCCNファミリー遺伝子の制御

    水川 朋美, 西田 崇, 明石 翔, 堀 彩花, 高柴 正悟, 上岡 寛, 滝川 正春, 久保田 聡

    岡山歯学会雑誌   38 ( 2 )   85 - 85   2019.12

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  • 歯科用接着性レジン系セメントを用いた補綴物装着によるアレルギー発症症例と検査の考察

    山城 圭介, 北川 雅恵, 岡 広子, 高柴 正悟

    日本口腔内科学会雑誌   25 ( 2 )   78 - 78   2019.12

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  • 急性期脳卒中患者における入院時評価項目と喀痰内の薬剤耐性菌検出状況に関する調査

    井上 裕貴, 松永 一幸, 山城 圭介, 高柴 正悟

    日本口腔内科学会雑誌   25 ( 2 )   109 - 109   2019.12

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  • 基幹病院⇔診療所間の医療情報連携の現実と理想

    高柴 正悟, 岡山大学病院歯周科:医療情報部専門委員会

    医療情報学連合大会論文集   39回   86 - 87   2019.11

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  • 急性期脳卒中患者における喀痰内の薬剤耐性菌検出状況と関与する背景因子

    井上 裕貴, 松永 一幸, 山城 圭介, 高柴 正悟

    日本未病システム学会学術総会抄録集   26回   131 - 131   2019.10

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  • 真菌二次代謝産物terreinはマウス骨粗鬆症モデルにおいて大腿骨吸収を抑制する

    坂井田 京佑, 大森 一弘, 中川 沙紀, 佐光 秀文, 山本 総司, 小林 寛也, 平井 公人, 山城 圭介, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   146 - 146   2019.10

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  • High Mobility Group Box 1(HMGB1)は間葉系幹細胞の遊走を介して抜歯窩の創傷治癒を促進する

    平井 杏奈, 井手口 英隆, 山城 圭介, 青柳 浩明, 鈴木 里紗, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   137 - 137   2019.10

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  • 二次性咬合性外傷を伴う重度慢性歯周炎患者への歯周組織再生治療の成功要因

    山本 直史, 新井 英雄, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   165 - 165   2019.10

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  • 広汎型中等度慢性歯周炎患者の24年経過からみたSPTの重要性

    福家 教子, 佐藤 佐智子, 新井 英雄, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   156 - 156   2019.10

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  • Porphyromonas gingivalisのPGN_0297の機能解析

    小野 晋太郎, 中山 真彰, 大原 直也, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   124 - 124   2019.10

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  • 【糖尿病専門医として知っておきたい歯周炎のこと】歯周病の新しい捉え方

    高柴 正悟

    月刊糖尿病   11 ( 4 )   46 - 55   2019.10

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  • 広汎型中等度慢性歯周炎患者に対して衛生管理しやすい口腔内環境を確立した症例

    田村 仁美, 清水 明美, 伊東 孝, 伊東 有希, 河野 隆幸, 高柴 正悟

    日本歯周病学会会誌   61 ( 秋季特別 )   168 - 168   2019.10

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  • 周期的伸展刺激と静水圧刺激に対するヒト歯根膜細胞の形態と配向の変化

    藤田 彩乃, 高柴 正悟

    岡山歯学会雑誌   38 ( 1 )   1 - 12   2019.6

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    ヒト歯根膜細胞の伸展刺激による配向性変化と、静水圧刺激による細胞形態変化について、in vitro機械刺激負荷制御システムを用いて検討した。結果、伸展刺激開始後6時間で伸展方向に対して60〜75°に配向し、静水圧刺激20MPa以上で細胞形態が変化し、40MPa以上で核形態も変化した。

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  • 歯周病原細菌を原因とするヒトと伴侶動物の犬における人獣共通感染症検査に関する研究

    田井 真砂子, 高柴 正悟

    岡山歯学会雑誌   38 ( 1 )   1 - 19   2019.6

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    ヒトと犬における歯周病原細菌の交差感染を調べるための検査方法として、ヒトで確立されているリアルタイムPCR法による細菌DNA検査およびELISA法による血清IgG抗体検査を用い、代表的な歯周病原細菌であるP.gingivalisとP.gulaeを対象とした検査を確立することを目的に研究を行った。リアルタイムPCRで推奨される増幅DNA長150bp以下のプライマーを作製するとともに、ELISAに用いる両細菌の超音波破砕抽出抗原を作製し、犬に対する有用性について検討した。結果、作製したプライマー・抗原は犬の歯周病検査にも有用と考えられた。

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  • 歯科関連行動とIgG抗体価で示す歯周病原細菌の感染度との関連の横断研究

    坪井 綾香, 高柴 正悟

    岡山歯学会雑誌   38 ( 1 )   1 - 10   2019.6

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    2008〜2015年に全国の日本歯周病学会会員(歯科医院)で市販の自己採血キットを用いて採取された血液から得られたIgG抗体価と、採血時の問診票に記載された歯科関連行動との関連性について検討した。対象は、全9286データ中、40歳未満と重複分を除外した5602データとした。検討の結果、年1回以上の歯科健診および歯石除去は歯周病原菌感染度と関連していることが明らかになり、この関連は特に女性と65歳未満者において顕著であった。

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  • コラーゲン結合型塩基性線維芽細胞増殖因子とコラーゲン基剤を用いた複合剤は水平性骨欠損における歯周組織再生を促進する

    中村 心, 高柴 正悟

    岡山歯学会雑誌   38 ( 1 )   1 - 14   2019.6

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    コラーゲン結合型bFGF(CB-bFGF)は整形外科領域において骨形成促進作用が報告されており、マウスの大腿骨骨折モデルに対してCB-bFGFにコラーゲン基剤を併用すると、bFGF単独に比べて骨折部の骨形成が有意に促進されたと報告されている。そこで、CB-bFGFとコラーゲン基剤を用いた複合剤を歯周組織再生療法に応用することを考えた。しかし、応用するには口腔の解剖学的特徴すなわち、創部が開放創となりやすく、材料が流出しやすいという点を考慮する必要がある。また、整形外科領域の報告にある長管骨は中胚葉由来であるのに対し、歯周組織は外胚歯由来であり、発生学的に異なる背景をもつ。これらのことを踏まえて複合剤の効果をin vitroとin vivoで検討した結果、bFGF単独に比べて有意に歯周組織再生を促進することが確認された。

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  • Rhizopus stolonifer NBRC 30816を用いて作製した大豆発酵食品テンペに含まれる抗菌性物質の単離と同定

    伊東 昌洋, 高柴 正悟

    岡山歯学会雑誌   38 ( 1 )   1 - 16   2019.6

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    テンペは、インドネシア原産のRhizopus属によって調製された伝統的な非塩漬け大豆発酵食品であり、発酵には、R.stolonifer、R.oligosporus、R.oryzaeがそれぞれ単独あるいは混合して使用される。テンペはグラム陽性菌に対して抗菌活性を示すと報告されていることから、著者等はテンペが口腔内細菌に対しても抗菌性をもつという仮説を立て、検証を行った。方法は、R.stolonifer、R.oligosporus、R.oryzaeそれぞれを用いて調製した3種のテンペについて、口腔内グラム陽性球菌に対する抗菌性を調べるとともに、各テンペに含まれる抗菌性物質の単離・同定を試みた。結果、3種のうちR.stoloniferで調製したテンペは抗菌性が最も強く、同テンペの粗抽出液は1mg/mL以上の濃度でS.mutansに対して抗菌性を示した。同テンペ中に含まれる抗菌性物質はリノール酸であると考えられた。

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  • 歯周組織の炎症と不妊の関連性を示唆するある侵襲性歯周炎患者の病態生理

    大森 一弘, 河野 隆幸, 小林 寛也, 新井 英雄, 山本 直史, 高柴 正悟

    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   150回   58 - 58   2019.5

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  • コラーゲン結合型塩基性線維芽細胞成長因子はコラーゲン基剤からの徐放によって歯周組織再生を促進する

    岡本 憲太郎, 中村 心, 伊東 孝, Siddiqui Yasir Dilshad, 美間 健彦, 内田 健太郎, 大森 一弘, 山本 直史, 松下 治, 高柴 正悟

    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   150回   113 - 113   2019.5

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  • 周期性好中球減少症を有する母娘に認められた重度歯周炎の症例

    二宮 雅美, 坂本 英次郎, 成石 浩司, 生田 貴久, 高木 亮輔, 畑中 加珠, 岡本 憲太郎, 小野 晋太郎, 高柴 正悟, 湯本 浩通

    日本歯周病学会会誌   61 ( 春季特別 )   164 - 164   2019.5

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  • 子宮全摘出・卵巣片側摘出直後から急性化した重度慢性歯周炎症例の治療と病態考察

    坂井田 京佑, 大森 一弘, 佐光 秀文, 小林 寛也, 高知 信介, 河野 隆幸, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 春季特別 )   157 - 157   2019.5

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  • 徹底した感染管理が垂直性骨欠損を改善する要因であった重度慢性歯周炎症例

    大久保 圭祐, 高知 信介, 本郷 昌一, 河野 隆幸, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   61 ( 春季特別 )   152 - 152   2019.5

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  • 細菌性コラゲナーゼのコラーゲン・アンカーと歯周組織再生への応用(Collagen anchors of bacterial collagenases and their application to periodontal tissue regeneration)

    松下 治, 美間 健彦, 後藤 和義, 山本 由弥子, Perry Caviness, Sakon Joshua, 小出 隆規, 内田 健太郎, 中村 心, 高柴 正悟

    日本細菌学雑誌   74 ( 1 )   84 - 84   2019.3

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  • 歯科から医療界へ発信する「口腔の感染・炎症・機能」に基づく歯周病の包括的臨床検査の確立

    高柴 正悟, 栗原 英見, 山崎 和久, 西村 英紀, 三辺 正人, 和泉 雄一

    日本歯科医学会誌   38   47 - 51   2019.3

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    医科歯科連携に深く関連する歯周病関連部分を、医療全般から理解される検査として再構築することによって、プロジェクト研究テーマB「歯科診療における臨床検査の新規開発」の一部へ対応させる。これによって、21世紀の医療において、歯科医療のみならず医療全般に変革をもたらす検査法と診断体系の開発に繋がる。ペリオドンタルメディシンの考え方が普及して、口腔と全身の疾患との関連(平成28年3月に日本歯周病学会が『歯周病と全身の健康』を刊行)の中から特に糖尿病治療体系に歯周病治療が取り入れられ、さらには抗菌剤のポケット内への投与が保険収載されるようにもなった。こうした展開を歯周病が関連する他の疾患へも広げることが、歯科医療のみならず医療全般の充実をもたらす。そこで、歯周病の発症と進行、口腔機能の喪失、全身への影響という観点から、(1)感染、(2)炎症、(3)咬合力・咀嚼率、といった3つの因子を包括的に把握する。これらの3分野の組み合せで歯周病の病状を捉えるように解析方法を開発するとともに、歯周病が関連する疾患への影響度の指標となるように解析方法を検討した。(著者抄録)

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  • 真菌二次代謝産物terreinはマウス歯周病モデルにおける歯槽骨吸収を抑制する

    佐光 秀文, 大森 一弘, 中川 沙紀, 坂井田 京佑, 山本 総司, 青柳 浩明, 小林 寛也, 大野 充昭, 平井 公人, 山城 圭介, 山本 直史, 高柴 正悟

    歯科薬物療法   38 ( 2 )   128 - 128   2019.3

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  • 専門外来最前線 侵襲性歯周炎に対する専門外来での対応 岡山大学病院・侵襲性歯周炎センターの取り組み

    大森 一弘, 高柴 正悟

    日本歯科評論   79 ( 3 )   141 - 147   2019.3

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  • 【歯周病と糖尿病・代謝疾患】歯周病と菌血症・感染症

    高柴 正悟

    内分泌・糖尿病・代謝内科   48 ( 2 )   108 - 113   2019.2

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  • 歯周病治療介入は誤嚥性肺炎を抑制できるのか? 歯周炎と誤嚥性肺炎の関係

    高柴 正悟

    日本臨床歯周病学会会誌   36 ( 2 )   40 - 42   2019.2

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  • 当院における成人先天性心疾患患者の口腔状態の現況(Current Oral Condition of Patients with Adult Congenital Heart Disease in ACHD Center/Okayama University Hospital)

    大森 一弘, 杜 徳尚, 高知 信介, 山本 直史, 赤木 禎治, 伊藤 浩, 高柴 正悟

    日本成人先天性心疾患学会雑誌   8 ( 1 )   142 - 142   2019.1

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  • 歯科診療室における情報提示の不備が引き起こす患者への影響

    安原啓太, 杉原太郎, 柳文修, 高柴正悟

    情報科学技術フォーラム講演論文集   18th   2019

  • Endodontic Management of a Bucco-Accessory Root Canal of a Maxillary Central Incisor: A Case Report

    ROSALIA Arias Martinez Zulema, SIDDIQUI Yasir Dilshad, YAMASHIRO Keisuke, SHINODA-ITO Yuki, YAMAMOTO Tadashi, TAKASHIBA Shogo

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   151st   2019

  • Porphyromonas gingivalisのPGN_0297の機能解析

    小野晋太郎, 中山真彰, 大原直也, 高柴正悟

    日本歯周病学会会誌(Web)   61   2019

  • 広汎型中等度慢性歯周炎患者に対して衛生管理しやすい口腔内環境を確立した症例

    田村仁美, 田村仁美, 清水明美, 清水明美, 伊東孝, 伊東有希, 河野隆幸, 高柴正悟

    日本歯周病学会会誌(Web)   61   2019

  • Functionalized Graphene Oxide Nanoparticles Protect Tooth Dentin from Decalcification besides Bactericidal Activity.

    ISLAM Nizami Mohammed Zahedul, NISHINA Yuta, YAMAMOTO Tadashi, SHINODA-ITO Yuki, TAKASHIBA Shogo

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   151st   2019

  • Porphyromonas gingivalisのジンジパインの機能発現におけるPGN_0297の役割

    小野 晋太郎, 高柴 正悟, 大原 直也

    岡山歯学会雑誌   37 ( 2 )   81 - 82   2018.12

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  • Porphyromonas gingivalis感染合併非アルコール性脂肪肝疾患に対する病態把握と治療の目安となる歯周組織検査所見の探索 多施設共同前向き観察研究

    鎌田 要平, 結束 貴臣, 清水 智子, 佐藤 五月, 青山 典生, 高柴 正悟, 中島 淳, 三辺 正人

    神奈川歯学   53 ( 抄録集 )   53 - 53   2018.12

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  • 岡山大学病院・糖尿病教育入院患者を対象とした医科歯科連携システムの概況

    清水 由梨香, 大森 一弘, 利根 淳仁, 高知 信介, 山本 直史, 和田 淳, 高柴 正悟

    岡山歯学会雑誌   37 ( 2 )   87 - 87   2018.12

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  • 歯科用ユニット給水管路汚染対策に向けた自動注水型試験機の有効性評価

    岡本 憲太郎, 大久保 圭祐, 伊東 孝, 伊東 昌洋, 田井 真沙子, 中村 心, 山口 唯菜, 塩田 康祥, 河田 有祐, 大森 一弘, 山本 直史, 高柴 正悟

    岡山歯学会雑誌   37 ( 2 )   83 - 84   2018.12

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  • 医療連携に必要な医療情報と医療連携レベル・患者個人レベルでのICT格差

    高柴 正悟, 医療情報部専門委員会

    医療情報学連合大会論文集   38回   158 - 159   2018.11

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  • 歯周炎罹患犬における歯周ポケット表面積推算法の確立と臨床的意義

    田村 和也, 田井 真砂子, 永原 未悠, 永原 美治, 高柴 正悟

    動物臨床医学会年次大会プロシーディング   39回 ( 2 )   131 - 132   2018.11

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  • コラーゲン結合型塩基性線維芽細胞成長因子とコラーゲン基剤を用いた複合剤の歯周組織再生への応用

    中村 心, 伊東 孝, 松下 治, 岡本 憲太郎, 美間 健彦, 内田 健太郎, Siddiqui Yasir Dilshad, 伊東 昌洋, 田井 真砂子, 大久保 圭祐, 山城 圭介, 大森 一弘, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   115 - 115   2018.10

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  • 歯周病の炎症度を示す臨床的検査基準値の検討

    井上 裕貴, 畑中 加珠, 大森 一弘, 山本 直史, 三辺 正人, 高柴 正悟, 平田 貴久, 山本 龍生, 内藤 徹, 山本 松男, 佐藤 秀一, 石幡 浩志, 稲垣 幸司, 三谷 章雄, 中島 啓介, 漆原 譲治

    日本未病システム学会学術総会抄録集   25回   108 - 108   2018.10

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  • Porphyromonas gingivalis感染合併非アルコール性脂肪肝疾患に対する病態把握と治療の目安となる歯周組織検査所見の探索 多施設共同前向き観察研究

    鎌田 要平, 結束 貴臣, 清水 智子, 佐藤 五月, 青山 典生, 小林 貴, 米田 正人, 畑中 加珠, 高柴 正悟, 岩崎 知之, 栗橋 健夫, 児玉 利朗, 田村 利之, 井野 智, 中島 淳, 三辺 正人

    日本歯周病学会会誌   60 ( 秋季特別 )   115 - 115   2018.10

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  • 真菌二次代謝産物(+)-terreinはマウス実験的歯周炎モデルにおける歯槽骨吸収を抑制する

    佐光 秀文, 大森 一弘, 中川 沙紀, 坂井田 京佑, 山本 総司, 青柳 浩明, 小林 寛也, 山城 圭介, 山本 直史, 高柴 正悟

    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   149回   150 - 150   2018.10

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  • 歯周病原細菌によるヒトと伴侶動物イヌとの人獣共通感染症検査の研究

    田井 真砂子, 伊東 孝, 平山 晴子, 矢田 範夫, 小川 寛人, 田村 和也, 伊東 有希, 大久保 圭祐, 伊東 昌洋, 中村 心, 岡本 憲太郎, 平井 公人, 山城 圭介, 大森 一弘, 山本 直史, 樅木 勝巳, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   135 - 135   2018.10

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  • 侵襲性歯周炎患者の血漿エクソソーム由来microRNAの発現解析

    高木 美奈, 山本 直史, 河村 麻理, 高知 信介, 山城 圭介, 大森 一弘, 江口 傑徳, 十川 千春, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   134 - 134   2018.10

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  • 侵襲性歯周炎患者の専門外来部門連携による包括的な治療と病態解析

    高知 信介, 久保 克行, 山本 直史, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   148 - 148   2018.10

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  • 歯周病患者における機能指標としての咀嚼機能検査の有用性について

    宮沢 春菜, 中島 貴子, 松川 由実, 清水 伸太郎, 古市 保志, 根本 英二, 高井 英樹, 中山 洋平, 小方 頼昌, 岩崎 拓也, 石原 裕一, 大井 麻子, 齋藤 淳, 藤原 千春, 村上 伸也, 畑中 加珠, 高柴 正悟, 武田 克浩, 藤田 剛, 栗原 英見, 山崎 和久

    日本歯周病学会会誌   60 ( 秋季特別 )   136 - 136   2018.10

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  • 歯根膜細胞における機械刺激による恒常性への影響

    藤田 彩乃, 森松 賢順, 西山 雅祥, 成瀬 恵治, 高柴 正悟

    日本歯周病学会会誌   60 ( 秋季特別 )   117 - 117   2018.10

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  • 歯周病の炎症度を示す臨床的検査基準値の検討

    井上 裕貴, 畑中 加珠, 大森 一弘, 山本 直史, 三辺 正人, 高柴 正悟, 平田 貴久, 山本 龍生, 内藤 徹, 山本 松男, 佐藤 秀一, 石幡 浩志, 稲垣 幸司, 三谷 章雄, 中島 啓介, 漆原 譲治

    日本未病システム学会学術総会抄録集   25回   108 - 108   2018.10

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  • Porphyromonas gingivalis感染合併非アルコール性脂肪肝疾患に対する病態把握と治療の目安となる歯周組織検査所見の探索 多施設共同前向き観察研究

    鎌田 要平, 結束 貴臣, 清水 智子, 佐藤 五月, 青山 典生, 小林 貴, 米田 正人, 畑中 加珠, 高柴 正悟, 岩崎 知之, 栗橋 健夫, 児玉 利朗, 田村 利之, 井野 智, 中島 淳, 三辺 正人

    日本歯周病学会会誌   60 ( 秋季特別 )   115 - 115   2018.10

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  • 化学療法施行中に口腔乾燥を訴えた進行再発乳がん患者の口腔内所見

    杉浦 裕子, 高橋 麻里子, 畑中 加珠, 田端 雅弘, 高柴 正悟

    日本歯科衛生学会雑誌   13 ( 1 )   126 - 126   2018.8

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  • 歯周炎と誤嚥性肺炎の関係

    高柴 正悟

    特定非営利活動法人日本臨床歯周病学会年次大会プログラム・講演抄録集   36回   61 - 62   2018.7

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