Hosoya, Makoto

写真a

Affiliation

School of Medicine, Otorhinolaryngology, Head and Neck Surgery （Shinanomachi）

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

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Academic Degrees 【 Display / hide 】

  • 医学博士, 慶應義塾大学, Coursework, 2017.03

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Research Areas 【 Display / hide 】

  • Life Science / Otorhinolaryngology

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Papers 【 Display / hide 】

  • Low-dose rapamycin-induced autophagy in cochlear outer sulcus cells

    Saegusa Chika, Hosoya Makoto, Nishiyama Takanori, Saeki Tsubasa, Fujimoto Chisato, Okano Hideyuki, Fujioka Masato, Ogawa Kaoru

    LARYNGOSCOPE INVESTIGATIVE OTOLARYNGOLOGY 5 （ 3 ） 520 - 528 2020.06

    ISSN  2378-8038

  • A phase I/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome/DFNB4

    Fujioka M., Akiyama T., Hosoya M., Kikuchi K., Fujiki Y., Saito Y., Yoshihama K., Ozawa H., Tsukada K., Nishio S.Y., Usami S.I., Matsunaga T., Hasegawa T., Sato Y., Ogawa K.

    Medicine （Medicine)  99 （ 19 ） e19763 2020.05

    ISSN  0025-7974

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    INTRODUCTION: Pendred syndrome (PDS)/DFNB 4 is a disorder with fluctuating and progressive hearing loss, vertigo, and thyroid goiter. We identified pathophysiology of a neurodegenerative disorder in PDS patient derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Given that there is no rational standard therapy for PDS, we planned a study to examine effects of low dose oral administration of sirolimus for the fluctuating and progressive hearing loss, and the balance disorder of PDS by daily monitor of their audio-vestibular symptoms. METHODS AND ANALYSIS: This is a phase I/IIa double blind parallel-group single institute trial in patient with PDS/DFNB4. Sixteen of outpatients with fluctuating hearing diagnosed as PDS in SLC26A4 genetic testing aged in between 7 and 50 years old at the time of consent are given either placebo or sirolimus tablet (NPC-12T). In NPC-12T placebo arm, placebo will be given for 36 weeks; in active substance arm, placebo will be given for 12 weeks and the NPC-12T for 24 weeks. Primary endpoints are safety and tolerability. The number of occurrences and types of adverse events and of side effects will be sorted by clinical symptoms and by abnormal change of clinical test results. A 2-sided 95% confidence interval of the incidence rate by respective dosing arms will be calculated using the Clopper-Pearson method. Clinical effects on audio-vestibular tests performed daily and precise physiological test at each visit will also be examined as secondary and expiratory endpoints. TRIAL REGISTRATION NUMBER: JMA-IIA00361; Pre-results.

  • A case report of Gorham-Stout disease diagnosed during the course of recurrent meningitis and cholesteatoma

    Hosoya M., Oishi N., Nishiyama J., Ogawa K.

    Journal of Otolaryngology - Head and Neck Surgery （Journal of Otolaryngology - Head and Neck Surgery)  49 （ 1 ） 18 2020.04

    ISSN  1916-0216

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    © 2020 The Author(s). Background: Gorham-Stout disease is a rare bone disorder. Here, we present a case of Gorham-Stout disease diagnosed during follow-up of a patient with cholesteatoma; the disease affected the temporal bone and other sites of the skull. To the best of our knowledge, this is the first report of Gorham-Stout disease diagnosed with recurrent cerebrospinal leakage after surgery to treat cholesteatoma. Case presentation: A 25-year-old male patient re-presented to our department for the first time in 7 years with otorrhea in the right ear and recurrent meningitis. The patient had a history of multiple surgeries for cholesteatoma and suffered from recurrent cerebrospinal fluid leakage, which initially was thought to be caused by recurrence of cholesteatoma. Therefore, skull base reconstruction was planned. However, the underlying cause was identified eventually as defects in the temporal bone caused by massive osteolysis due to Gorham-Stout disease. Skull base reconstruction was abandoned because the osteolysis was considered to be progressive. Conservative treatment with infectious control was implemented as an alternative. Conclusion: This case describes unusual temporal bone osteolysis after cholesteatoma surgery and the importance of considering the possibility of multiple concurrent diseases in such individuals. The distinguishing features of this case are the fact that the temporal bone had disappeared, and deconstruction was complicated by infection and inflammation caused by cholesteatoma, surgical invasion, and Gorham-Stout disease. Appropriate diagnosis saved the patient from ineffective multiple surgeries for cerebrospinal fluid leakage or cholesteatoma, and improved his quality of life.

  • A rare case of bifurcated chorda tympani

    Kasahara K., Hosoya M., Oishi N., Ogawa K.

    Journal of International Advanced Otology （Journal of International Advanced Otology)  16 （ 1 ） 141 - 144 2020.04

    ISSN  13087649

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    © 2020, AVES. All rights reserved. Preservation of the chorda tympani is important in middle ear surgery to prevent dysgeusia postoperatively. However, determining the exact course of the chorda tympani before surgery is not always possible, especially in cases with accompanying malformations. In this report, we pre-sented an extremely rare case of bifurcation of the chorda tympani in a 15-year-old male patient. We performed tympanoplasty for a middle ear malformation with conductive hearing loss. During the operation, we noticed and carefully preserved the bifurcated chorda tympani. The patient did not develop dysgeusia postoperatively. Appropriate handling and understanding of the anomalous chorda tympani preserved the patient’s sense of taste and hence quality of life.

  • A new training method for velopharyngeal dysfunction: Self-inhalation for hypernasality

    Kobayashi R., Tsunoda K., Takazawa M., Ueha R., Hosoya M., Fujimaki Y., Nito T., Yamasoba T.

    Auris Nasus Larynx （Auris Nasus Larynx)  47 （ 2 ） 250 - 253 2020.04

    ISSN  03858146

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    © 2019 Elsevier B.V. Objective: There are various methods to treat velopharyngeal dysfunction including surgery and rehabilitation therapy. Even if a rehabilitation program is effective, the evaluation of its efficacy remains subjective. In this paper, we propose a new method of rehabilitation training for velopharyngeal dysfunction focusing on the objective peak inspiratory flow (PIF) rate. Methods: Four patients, who were diagnosed with velopharyngeal dysfunction without cleft palate at ENT clinic of the National Hospital Organization, Tokyo Medical Center, participated in this study. All patients underwent our original rehabilitation program for velopharyngeal dysfunction, a method using the In-Check Dial, Turbohaler model. As a self-training rehabilitation program, we asked them to inhale forcefully 10 times daily at home using the In-Check Dial to increase the value of PIF rate for 3 months. We measured the patients’ PIF rates with the In-Check Dial at the ENT clinic at the initial visit and after the 3-month training. Results: The PIF rates of the four patients without nasal clips were higher than the rates with nasal clips at the initial visit. After the training, PIF rate without a nasal clip of all patients increased than the rate at the initial visit, which represented significant difference (P < 0.05). Also, after 3 months, PIF rate without a nasal clip was higher or equal than the rates with a nasal clip at the initial visit except one case. Naso-pharyngo-laryngeal fiberscopy did not detect salivary pooling around larynx and mirror fogging test did not show nasal escape in the three of four patients after 3 months of training. All reported improvement in dysphagia and dysarthria. Conclusion: This new method can be used not only to evaluate velopharyngeal function but also as an effective self-training treatment.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 【フローチャートと検査一覧で　ひと目でわかる耳鼻咽喉科診療】耳科編　耳鳴・聴覚過敏　急性耳鳴,慢性耳鳴,無難聴性耳鳴,心因性疾患

    細谷 誠, 神崎 晶

    耳鼻咽喉科・頭頸部外科 ((株)医学書院)  92 ( 5 ) 053 - 058 2020.04

    ISSN  0914-3491

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    ＜文献概要＞ここを押さえておこう　●耳鳴・聴覚過敏の診断には問診が重要である.●耳鼻咽喉科疾患以外の基礎疾患および精神疾患の除外が必要.●慢性耳鳴・聴覚過敏に対しては,Tinnitus Retraining Therapyを検討する.

  • 【難聴を治す-2020年版】感音難聴とiPS創薬

    藤岡 正人, 細谷 誠

    JOHNS ((株)東京医学社)  36 ( 1 ) 101 - 104 2020.01

    ISSN  0910-6820

  • ヒトiPS細胞を用いた内耳疾患研究および治療法開発

    細谷 誠, 藤岡 正人

    日本耳鼻咽喉科学会会報 ((一社)日本耳鼻咽喉科学会)  122 ( 12 ) 1508 - 1515 2019.12

    ISSN  0030-6622

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    感音難聴に対する治療法の開発は、診断学の向上に比べて進捗が乏しい。その一つの原因は生検による患者内耳細胞の直接の観察が解剖学的に困難なことにある。これまでに代替手法として細胞株やモデル動物を用いた研究が展開され、有用な情報をもたらしてきたものの、いまなお未解明な科学的課題も多数残されている。近年、既存の手法で克服できなかった科学的課題に対し、ヒト細胞および組織の代替となる新しい研究ツールとして、ヒトiPS細胞を用いた検討が医学のさまざまな分野で展開されている。山中らによって2006年にマウスで最初に報告されたiPS細胞だが、続く2007年にはヒトiPS細胞の樹立方法が報告され、約十年の間にその応用方法は飛躍的な発展を遂げている。本細胞は体内のありとあらゆる細胞に分化誘導可能という特徴を持つ。この性質を利用することによって、体外で目的の細胞を作成し、細胞移植治療や病態研究、さらには創薬研究への応用が可能である。国内においても、すでに網膜や脳に対する移植が臨床研究レベルで行われているほか、複数の疾患においてiPS細胞を用いて発見された治療薬候補の臨床検討が開始されている。ヒトiPS細胞を用いた研究は、内耳疾患研究および治療法開発にも応用が可能である。ほかの臓器と同様に、本細胞からの体外での内耳細胞誘導が可能であり、誘導されたヒトiPS細胞由来内耳細胞を用いた研究が展開できる。内耳研究においてもこれまでに、(1)細胞治療への応用、(2)内耳病態生理研究への応用、(3)創薬研究への応用、がなされており、そのほかにも老化研究や遺伝子治療法の開発への貢献などさまざまな可能性が期待されている。本稿では、ヒトiPS細胞の内耳研究への応用およびiPS細胞創薬の展望を概説するとともに、最新の試みを紹介する。(著者抄録)

  • Correction: ClinGen expert clinical validity curation of 164 hearing loss gene–disease pairs (Genetics in Medicine, (2019), 21, 10, (2239-2247), 10.1038/s41436-019-0487-0)

    DiStefano M.T., Hemphill S.E., Oza A.M., Siegert R.K., Grant A.R., Hughes M.Y., Cushman B.J., Azaiez H., Booth K.T., Chapin A., Duzkale H., Matsunaga T., Shen J., Zhang W., Kenna M., Schimmenti L.A., Tekin M., Rehm H.L., Tayoun A.N.A., Amr S.S., Abdelhak S., Alexander J., Avraham K., Bhatia N., Bai D., Boczek N., Brownstein Z., Burt R., Bylstra Y., del Castillo I., Choi B.Y., Downie L., Friedman T., Giersch A., Goh J., Greinwald J., Griffith A.J., Hernandez A., Holt J., Hosoya M., Ying L.J., Jain K., Kim U.K., Kremer H., Krantz I., Leal S., Lewis M., Liu X.Z., Low W., Lu Y., Luo M., Masmoudi S., Ming T.Y., Moreno-Pelayo M.A., Morín M., Morton C., Murray J., Mutai H., Nara K., Pandya A., Pei-Rong S.K., Smith R.J.H., Jamuar S.S., Suer F.E., Usami S.I., Van Camp G., Yamazawa K., Yuan H.J., Black-Zeigelbein E., Zhang K.

    Genetics in Medicine (Genetics in Medicine)  21 ( 10 )  2019.10

    ISSN  10983600

    　View Summary

    © 2019, American College of Medical Genetics and Genomics. In the original version of this Article, the address for affiliation 8, Division of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center, Tokyo, Japan, was incorrectly given as Laboratory of Auditory Disorders and Division of Hearing and Balance Research, Tokyo, Japan. Furthermore, the address for affiliation 9, Medical Genetics Center, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan, was incorrectly given as Medical Genetics Center, National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan. They have now been corrected in both the PDF and HTML versions of the Article.

  • 高齢者の聴覚と暮らし方と健康に関する学術調査(第2報)　老人性難聴のリスクファクターの探索

    忰田 かおり, 藤岡 正人, 北村 充, 堀 明美, 薬師丸 令子, 野口 勝, 粕谷 健人, 西山 崇経, 石川 徹, 細谷 誠, 鈴木 成尚, 長谷部 夏希, 岡本 康秀, 小川 郁

    Audiology Japan ((一社)日本聴覚医学会)  62 ( 5 ) 568 - 568 2019.10

    ISSN  0303-8106

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 進化動物学的知見からの発生時間軸の種差を応用した聴覚器発生の高時間分解解析

    2021.07
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Exploratory), Principal investigator

  • コモンマーモセットを用いた内耳研究プラットフォームの創生

    2020.04
    -
    2023.03

    Keio University, Grant-in-Aid for Scientific Research (B), No Setting

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    内耳研究には齧歯類や鳥類・ゼブラフィッシュなどの非ヒト非霊長類モデル動物が用いられるが、これらを駆使しても解決できない科学的課題がときに存在し、その原因の一つにモデル動物とヒトの間の種差の存在が指摘されている。とくに内耳研究では、種差の問題の克服のための新しい研究ツールの確立が求められていた。
    本計画ではコモンマーモセット内耳研究を、胎生期から高齢個体に到るまでの全ライフスパンに拡張する。内耳発生学的研究および加齢性難聴研究プラットフォームとして確立すると同時に、遺伝性難聴モデル動物としての拡充を図るべく分子生物学的手法を用いて組織解剖学的な詳細な検討を行い、霊長類内耳細胞の網羅的な解析を行う。

  • Binaural brain mechanism of bilateral cochlear implants with auditory neuropathy

    2020.04
    -
    2023.03

    独立行政法人国立病院機構(東京医療センター臨床研究センター), Grant-in-Aid for Scientific Research (C), No Setting

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    1996年に新しい聴覚障害として研究代表者の加我がAuditory Nerve Disease (AND)、米国のStarrがAuditory Neuropathy (AN)としてそれぞれ発表したが、現在では同一の新しい聴覚障害として世界的に認知されている。また2008年には本疾患の先天性障害について米国のNorthernらがANSDとして提案した。現在、ANSDの効果的な治療の主たる方法は両側人工内耳手術である。しかし、ANSDはsynaptopathyとneuropathyの少なくとも2タイプがあり、両耳聴が中枢聴覚で成立しているか全く不明で、単耳聴と両耳聴成立の有無を明らかにすることで病態生理についての解明に取り組み、ANSDの小児と成人患者の聴覚・言語認知能力の解明に貢献する。

  • 多層オミックスとiPS技術,霊長類モデルを駆使した加齢性難聴への挑戦

    2019.06
    -
    2022.03

    Keio University, Challenging Research (Pioneering), No Setting

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    難聴は65歳以上の高齢者の1/3、世界で約5億人が罹患し、QOLの低下のみならず認知症や高齢者のうつ病の危険因子ともされ、未曾有の超高齢社会を迎えた本邦での健康寿命延伸には欠かせない課題である。加齢で進行する難聴は、音刺激の感覚受容器である内耳に原因があるとされるが、内耳は側頭骨の奥深くに存在して生検できず、詳細なメカニズムは不明な点が多い。
    本研究では、多層オミックス解析と霊長類モデルを駆使して、この治療法不在の疾患に迫り、原因の一端を解明し、最終的には難聴治療・予防法の開発を目指す。

  • Development of novel therapeutics for the cochlear hearing impairments by using hiPSCs and common marmoset models

    2018.04
    -
    2021.03

    Keio University, Grant-in-Aid for Scientific Research (A), No Setting

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2024

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2023

  • LECTURE SERIES, OTORHINOLARYNGOLOGY

    2022

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