Faculty Profiles - TAKASHIBA Shogo

Papers - TAKASHIBA Shogo

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根尖性歯周炎に起因した放射線性下顎骨骨髄炎に対して保存的治療を行い良好な経過を得た一症例 Reviewed

工藤値英子, 水川展吉, 中川沙紀, 柳文修, 江口元治, 松香芳三, 吉岡裕也, 高柴正悟

日本歯科保存学雑誌 58 ( 5 ) 425 - 434 2015.10

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

目的:放射線が照射された顎骨では,骨の細胞活性能が低下し,細菌感染により骨髄炎を発症しやすい.今回,下咽頭癌に対する放射線治療の既往がある患者に発症した46の根尖性歯周炎に起因する放射線性下顎骨骨髄炎に対して,抗菌薬投与と感染根管治療の併用によって保存的治療を行い,良好な経過を得た症例について報告し,その対処法を考察する.症例の概要:患者は58歳男性.下咽頭癌に対して,岡山大学病院耳鼻咽喉科と放射線科にて2006年11月から2007年1月まで化学放射線療法を受けた.2010年5月初旬に右側下顎部に疼痛を自覚していたところ,定期検査時の18F-fluoro-deoxyglucose positron emission tomography-computed tomography(FDG-PET/CT)検査にて,下顎右側にFDG異常集積が認められた.当院歯周科および口腔外科にて,46の根尖性歯周炎に起因する放射線性下顎骨骨髄炎と診断された.口腔外科にて抗菌薬および鎮痛剤の投与が継続され,同科からの依頼により当科にて46の根管治療を継続した.治療経過:46に対して感染根管治療を継続するも,右側下顎部の自発痛が続き,弓倉症状による強い打診痛の範囲が46から前方へと波及した.下顎骨に放射線治療の既往があるため,下顎骨骨髄の減圧を目的とした外科処置を行うことができなかった.そこで,外科処置に代わる減圧手段として,MR画像上における浮腫性変化を示す範囲内の全歯に対して根管開放を行い,並行して耳鼻咽喉科での抗癌剤中止に加えて口腔外科での抗菌薬投与を継続した.さらに,これらの歯を咬合させないよう安静に維持することで,急性症状が軽快して骨髄炎を沈静化させることができた.その後から現在まで,下顎部は良好に経過している.考察および結論:46の根尖性歯周炎に起因する放射線性下顎骨骨髄炎に対して,抗菌薬投与と感染根管治療の併用によって良好な経過を得ることができた.顎骨への放射線照射を行う患者において,放射線治療前に医科歯科連携下による歯性感染巣除去を行い,顎骨骨髄炎を予防することが重要である.(著者抄録)

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

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

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

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.

DOI： 10.1007/s10266-014-0172-3

PubMed

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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. Reviewed 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

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

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.

DOI： 10.1111/jre.12227

PubMed

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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

CBCTの活用に関するプロジェクト研究歯周組織再生治療の評価に向けたCBCTの活用 Reviewed

栗原英見, 和泉雄一, 村上伸也, 沼部幸博, 高柴正悟

日本歯科医学会誌 34 89 - 93 2015.3

Authorship：Last author,　Corresponding author Language：Japanese Publisher：日本歯科医学会

歯周組織再生治療を成功に導くには、歯周炎による歯槽骨欠損の幅、深さ、角度、そして残存する骨壁数を術前に正確に把握することによる適応症診断が重要である。歯科用Cone beam computed tomography(CBCT)は、従来の診査方法では困難であった口腔内の3次元的形態を描出できるという点で、歯科領域で頻繁に使用されているものの、歯周組織再生治療の評価に有効であるかの十分なコンセンサスは得られてない。そこで本研究では、ブタ歯槽骨に規格化した骨欠損を人工的に作製し、評価項目毎の実測値とCBCT画像上の長さ(画像値)の誤差を比較し、歯周組織再生治療の評価への有用性を検討した。骨欠損の規格化は、デジタルノギスでの測定下でブタ下顎骨を技工用バーで削合することによって行った。各条件の骨欠損(n=3)の実測値とCBCTによる画像値を比較した結果、評価項目全体の誤差の平均は0.32mmで、骨欠損実測値の大小に関わらず一定の傾向はなかった。また、頬側骨の厚さが1mmあれば、CBCTで描出することは可能だった。さらに、骨欠損の体積は、頬側骨の厚さが2mmに近づくにつれ、その誤差は減少した。以上の結果から、CBCTは、骨欠損の大きさを正確に計測することは難しいが、骨欠損の位置や骨欠損の壁数を把握できることが明らかになった。すなわち、CBCTは歯周組織再生治療を行う際の骨欠損を診断するための一つの診査方法として有効であると考える。(著者抄録)

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岡山県内ベーチェット病患者の口腔内状態に対する医師の把握状況に関するアンケート調査 Reviewed

工藤値英子, 若林宏, 小谷朋子, 高柴正悟

日本口腔検査学会雑誌 7 ( 1 ) 35 - 41 2015.3

Authorship：Last author,　Corresponding author Language：Japanese Publisher：(一社)日本口腔検査学会

目的:岡山県におけるベーチェット病患者の口腔内状態に対する医師の把握状況を調査することを目的とした。方法:岡山県から岡山大学病院腎臓・糖尿病・内分泌内科へ提供された「ベーチェット病登録医療機関」(特定疾患申請時に「受診予定」として患者が登録した医療機関)から抽出した262施設に対して,無記名アンケートを実施した。結果:回答のあった123施設中,「ベーチェット病と口腔内感染巣の関連性」に関心のある施設は約6割の73施設であった。また,ベーチェット病患者が通院中の施設は63施設で,通院患者総数は191人であった。そのうち,歯科医療施設へ通院中のベーチェット病患者は21人であった。「口腔衛生状態不良と思われるベーチェット病患者はいますか?」との質問に対して,「はい」との回答は63施設中8施設,「いいえ」は34施設,そして「不明」が21施設であった。さらに,歯科治療によってベーチェット病の症状に変化を生じた患者を経験した施設は5施設のみで,それらの症状は,悪化したものが眼症状,口内炎,皮膚症状,そして発熱であり,改善したものが口内炎であった。結論:本アンケート調査から,医科におけるベーチェット病患者の口腔内状態の把握度が低い可能性が推察される。また,歯科治療によってベーチェット病の症状に変化が生じる可能性がある。これらから,口腔領域の簡易検査を充実させた医科歯科連携による口腔内感染管理システムが重要であることを認識した。(著者抄録)

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Involvement of an Skp-like protein, PGN_0300, in the type IX secretion system of Porphyromonas gingivalis Reviewed

Taguchi, Y., Sato, K., Yukitake, H., Inoue, T., Nakayama, M., Naito, M., Kondo, Y., Kano, K., Hoshino, T., Nakayama, K., Takashiba, S., Ohara, N.

Infection and Immunity 84 ( 1 ) 230 - 240 2015

Publishing type：Research paper (scientific journal) Publisher：American Society for Microbiology

<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.

DOI： 10.1128/IAI.01308-15

Interdisciplinary orthodontic treatment for a patient with generalized aggressive periodontitis: Assessment of IgG antibodies to identify type of periodontitis and correct timing of treatment Reviewed

Ishihara, Y., Tomikawa, K., Deguchi, T., Honjo, T., Suzuki, K., Kono, T., Kuboki, T., Kamioka, H., Takashiba, S., Yamashiro, T.

American Journal of Orthodontics and Dentofacial Orthopedics 147 ( 6 ) 2015

Group A. Consensus paper. Plaque control--home remedies practiced in developing countries Reviewed

Ciancio, S., Slot, D.E., Van Dyke, T., Al Bayaty, F., Aswapati, N.W., Joshi, V., Kendall, K., Leung, K., Patel, N., Pradhan, S., Senevirante, C., Takashiba, S., Vidhale, P.

Journal of the International Academy of Periodontology 17 ( 1 ) 2015

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

Predictors of improved functional outcome in elderly inpatients after rehabilitation: a retrospective study Reviewed

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

Clinical Interventions in Aging 2133 - 2133 2014.12

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 Reviewed

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

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

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

Clinical Case Reports 2 ( 6 ) 286 - 295 2014.12

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

Mandai, H, Omori, K, Yamamoto, D, Tsumura, T, Murota, K, Yamamoto, S, Mitsudo, K, Ibaragi, S, Sasaki, A, Maeda, H, Takashiba, S, Suga, S

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

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

Ebinuma, T., Soga, Y., Sato, T., Matsunaga, K., Kudo, C., Maeda, H., Maeda, Y., Tanimoto, M., Takashiba, S.

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

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

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

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.

DOI： 10.1111/jre.12106

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ある侵襲性歯周炎患者の26年間における歯周病治療の経過血清IgG抗体価による歯周病原細菌感染度のモニタリング Reviewed

内藤仁美, 工藤値英子, 目黒道生, 成石浩司, 伊東孝, 前田博史, 高柴正悟

日本歯周病学会会誌 56 ( 2 ) 217 - 226 2014.6

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

ある広汎型侵襲性歯周炎患者(女性)の24歳時からの26年間に及ぶ歯周治療経過を、臨床的観点と細菌学的・免疫学的な観点から追った。その間、患者には結婚、転居、出産、そして育児といったライフステージの変化があった。そこで、このライフステージによる生活習慣の変化が歯周病の病態に影響を与える可能性を考えて、動的治療期からSupportive Periodontal Therapy(SPT)期に渡って臨床症状が出現する前に病態変化を捉えようと、歯周病原細菌感染度を歯周病原細菌に対する血清IgG抗体価を用いてモニタした。この治療経過における患者の病態とSPT期における継続的な受診支援に関して考察し、10代後半から20代前半に発症する侵襲性歯周炎患者の長期管理法を提案する。この方法は、細菌の持続感染による疾患の活動性を把握するために用いた血清IgG抗体価検査による、口腔内の感染管理に注目するものである。(著者抄録)

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DNA normalizationを応用した高感度な細菌叢解析法の検討 Reviewed

松永一幸, 工藤値英子, 河田有祐, 前田博史, 高柴正悟

日本口腔検査学会雑誌 6 ( 1 ) 23 - 30 2014.3

Authorship：Last author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本口腔検査学会

DNA normalizationを応用した高感度な細菌叢解析法(T-RFLP)について検討した。A.actinomycetemcomitans(Aa)、P.gingivalis(Pg)、P.intermedia(Pi)のDNA濃度比を、試料1で100:10:1、試料2で10:0:1、試料3で1:1:1に設定した。Nsp IによるT-RFLP法パターンでは、Normalization前において、試料1および試料2ではDNA濃度が最も高いAaのみが検出された。Normalization後は、試料1ではAa、Pg、Piの3菌種、試料2ではAaおよびPiの2菌種を検出した。試料3では、Normalization前後で3菌種全ての検出を確認した。また、Normalization後の検出率は、いずれも陽性コントロールの結果と一致した。

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

Nakao, R., Takashiba, S., Kosono, S., Yoshida, M., Watanabe, H., Ohnishi, M., Senpuku, H.

Microbes and Infection 16 ( 1 ) 6 - 16 2014.1

Osteogenic differentiation regulated by Rho-kinase in periodontal ligament cells Reviewed

Yamamoto, T., Ugawa, Y., Yamashiro, K., Shimoe, M., Tomikawa, K., Hongo, S., Kochi, S., Ideguchi, H., Maeda, H., Takashiba, S.

Differentiation 88 ( 2-3 ) 2014

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