東北大学研究者紹介

研究者詳細

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日本語 English

顔写真

ホンクラ　ヨウヘイ

本藏　陽平

Yohei Honkura

所属

病院　感覚器・理学診療科　耳鼻咽喉科

職名

講師

学位

博士（医学）（東北大学）

researchmap

https://researchmap.jp/yohei-honkura

J-GLOBAL ID

202001019854587047

研究キーワード 4

加齢性難聴
酸化ストレス
難聴
内耳

研究分野 1

ライフサイエンス / 耳鼻咽喉科学 /

論文 137

Seafood and polyunsaturated fatty acid intake and age-related hearing loss: a cross-sectional study conducted in Japan. 国際誌

Jun Suzuki, Hiroki Tozuka, Hiyori Takahashi, Ikuko N Motoike, Miyuki Sakurai, Yuta Kobayashi, Gosuke Watarai, Mana Kogure, Tetsuaki Kawase, Yohei Honkura, Ryoukichi Ikeda, Kengo Kinoshita, Naoki Nakaya, Taku Obara, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

The journal of nutrition, health & aging　30　(11)　100971-100971　2026年9月4日

DOI： 10.1016/j.jnha.2026.100971 　

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BACKGROUND: Age-related hearing loss (ARHL) is a common condition associated with dementia, social isolation, and reduced quality of life. N-3 polyunsaturated fatty acids (N-3 PUFAs), mainly derived from seafood, have been hypothesized to protect against ARHL through anti-inflammatory and antioxidant effects. However, evidence remains inconsistent. This cross-sectional study examined the association of seafood and dietary fatty acid intakes with ARHL in a Japanese population with high seafood consumption. METHODS: A total of 13,908 adults aged 50-79 years from the Tohoku Medical Megabank Project Cohort Study were included. Hearing thresholds were measured by pure-tone audiometry at 500, 1,000, 2,000, and 4,000 Hz. Dietary intake was assessed using a validated food frequency questionnaire. Seafood, N-3 PUFA, and saturated fatty acid (SFA) intakes were categorized into quartiles. Multivariable linear regression was used to estimate adjusted mean differences in hearing thresholds. RESULTS: In men, higher SFA intake was significantly associated with lower hearing thresholds at 1,000 Hz (Q4 vs. Q1: β = -2.23 dB HL, 95% CI: -3.437 to -1.023) and for pure-tone average (β = -1.704 dB HL; 95% CI, -2.872 to -0.536). Seafood and N-3 PUFA intakes were not significantly associated with hearing thresholds. In women, no significant associations were observed. CONCLUSION: In this population with high seafood consumption, seafood and N-3 PUFA intakes were not associated with hearing thresholds. Low SFA intake may be associated with higher hearing thresholds in Japanese men, suggesting that the relationship between dietary fatty acids and ARHL may be complex and may differ by sex.
Age- and Sex-Specific Better-Ear Hearing Thresholds in Community-Dwelling Japanese Adults.

Jun Suzuki, Hiroki Tozuka, Hiyori Takahashi, Ikuko N Motoike, Miyuki Sakurai, Yuta Kobayashi, Tetsuaki Kawase, Yohei Honkura, Ryoukichi Ikeda, Koichiro Wasano, Kengo Kinoshita, Naoki Nakaya, Taku Obara, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

Geriatrics & gerontology international　26　(8)　e70775　2026年8月

DOI： 10.1111/ggi.70775 　
Distinct delayed development of the basisphenoid-ethmoid interface in human fetuses: a histological study using human fetuses. 国際誌

Ai Hirano-Kawamoto, Masahito Yamamoto, Yohei Honkura, Gen Murakami, Shogo Hayashi, Yukio Katori

Anatomy & cell biology　2026年4月30日

DOI： 10.5115/acb.25.299 　

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In non-human primates, the presphenoid-ethmoid synchondrosis (PSept) functions as a major growth center of the midline skull base, yet whether humans possess a developmental analogue remains unresolved. To clarify whether a human counterpart exists, we re-examined the basisphenoid-ethmoid (SPH-ETH) junction using sagittal histological sections from 20 human fetuses (11-39 weeks) preserved in the Akita University collection. At 15-16 weeks, chondrocytes in the anterior portion of the SPH-immediately anterior to the pituitary fossa-became slender or irregularly shaped with increased extracellular matrix, forming a distinct low-density zone (<8 cells per 0.1 mm2) compared with adjacent SPH cartilage (>15 cells per 0.1 mm2). In late-term fetuses (≥29 weeks), this zone expanded vertically to reach both the superior and inferior perichondria and appeared less basophilic, often containing fibrous or mesh-like structures. Notably, two late-term fetuses (35 and 39 weeks) displayed an additional anterior ossification center immediately in front of this low-density zone, creating a bipolar ossification pattern analogous to that of the PSept in non-human primates. In these specimens, parallel collagen bundles oriented supero-inferiorly were also observed across the interface. Taken together, these findings identify a reproducible, sparsely populated, fiber-containing cartilage region at the human SPH-ETH junction, frequently associated with an anterior ossification center. We propose that this region represents the human analogue of the PSept and that the "transient presphenoid" becomes incorporated into the definitive ethmoid during late fetal development.
Relationship between age-related hearing loss and alcohol consumption in a Japanese population. 国際誌

Hiyori Takahashi, Jun Suzuki, Ikuko N Motoike, Miyuki Sakurai, Yuta Kobayashi, Gosuke Watarai, Hiroki Tozuka, Mana Kogure, Tetsuaki Kawase, Yohei Honkura, Ryoukichi Ikeda, Kengo Kinoshita, Naoki Nakaya, Taku Obara, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Fuse, Masayuki Yamamoto, Yukio Katori

Scientific reports　16　(1)　336-336　2025年12月2日

DOI： 10.1038/s41598-025-29634-7 　

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Age-related hearing loss (ARHL) has a multifactorial pathogenesis, and the influence of alcohol consumption on it is controversial. This cross-sectional study investigated the association between ARHL and alcohol consumption by using cohort data from Tohoku Medical Megabank Project, including self-reported questionnaires and pure-tone audiometry thresholds (500, 1000, 2000, and 4000 Hz). ARHL was defined as a threshold of > 25 dB in the better ear. Multiple logistic regression analyses (age 50-79 y; 5,219 men and 9,266 women) were conducted separately for men and women and indicated that daily alcohol consumption levels of 60-80 and ≥ 80 g were significantly associated with increased odds of ARHL at 4,000 Hz in men (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.05-1.94; OR 1.55; 95% CI 1.12-2.16; respectively); consumption of 10-20 g was significantly associated with reduced odds of ARHL at 4,000 Hz in women (OR 0.81; 95% CI 0.68-0.96). Assessment of drinking-related single nucleotide polymorphisms suggested that the effect of alcohol on ARHL may differ by genotype. Our findings suggest a sex-specific association between alcohol consumption and ARHL; heavy drinking is a potential risk factor in men, whereas moderate drinking may have a protective effect in women.
水中内視鏡下pluggingを施行した上半規管裂隙症候群30例とくに耳管開放症ととの鑑別診断について

川村善宣, 野村有理, 野村和弘, 小林俊光, 大島英敏, 大島猛史, 池田怜吉, 本蔵陽平, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　35回　243-243　2025年10月
出版者・発行元： (一社)日本耳科学会
Music Listening Habits and Auditory Functions in Medical College Students.

Tomoyasu Ishida, Jun Suzuki, Takeshi Sato, Tetsuya Oishi, Yohei Honkura, Ryoukichi Ikeda, Yukio Katori

JMA journal　8　(3)　799-808　2025年7月15日

DOI： 10.31662/jmaj.2025-0016 　

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INTRODUCTION: Early detection of hearing impairment in young adults and raising social awareness of preventive measures are essential to mitigate the negative impact on individuals' quality of life and reduce the societal costs associated with hearing impairment. This study investigated the music listening habits of medical college students using audiological function tests to assess their impact on young adults' hearing functions. METHODS: We recruited 77 healthy volunteers who underwent a comprehensive assessment, including a questionnaire on music listening habits, pure-tone audiometry (PTA), tympanometry, extended high-frequency (EHF) audiometry, and loudness discomfort level (LDL) tests. Furthermore, we measured preferred music listening levels (PMLs). The association between music listening habits and PMLs and the results of various auditory function tests were examined. RESULTS: Among the 77 participants, 60 were men, and 17 were women, with a median age of 23 years. All participants exhibited a mean hearing threshold of less than 25 dB HL on PTA. Sixty-six (85.7%) participants used earphones/headphones daily, with a median usage duration of 2.0 hours. The correlations between the duration of earphones/headphones usage, EHF thresholds, and LDLs were not significantly different. The correlation between the duration of earphones/headphones usage and PMLs was weakly positive (r = 0.2772). A stronger positive correlation (r = 0.4625) was observed when focusing on 23 participants with high LDL values. CONCLUSIONS: The positive correlation between the duration of earphones/headphones usage and PMLs suggested that inappropriate music listening habits might synergistically act as risk factors for hearing impairment in young adults.
【高齢者と聴覚】聴こえを支える地域連携宮城県における加齢性難聴に関する啓発事業と聴力スクリーニングアプリ開発の試み

佐藤剛史, 鈴木淳, 角田梨紗子, 本藏陽平, 冨田尚希, 香取幸夫

日本老年医学会雑誌　62　(3)　290-297　2025年7月
出版者・発行元： (一社)日本老年医学会
ISSN：0300-9173
Development of the occipitopetrosal junctions: A histological study using human fetuses. 国際誌

Ai Hirano-Kawamoto, Yohei Honkura, Chun-Ai Li, Samuel Verdugo-López, Gen Murakami, Jose Francisco Rodríguez-Vázquez, Yukio Katori

Anatomical record (Hoboken, N.J. : 2007)　2025年5月14日

DOI： 10.1002/ar.25687 　

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The temporal bone petrosa is connected to the occipital bone at two sites: one junction with the basilar part (medial junction) and another with the lateral part (lateral junction). Using histological specimens from 45 human fetuses (approximately 7-39 weeks of gestational age or GA), we aimed to describe possible changes in histology and topographical anatomy during processes toward the ossified union. In the early term, the junctions were characterized by dense mesh-like fibers that likely corresponded to the thickened basal laminae of the composite cartilage cells. Notably, the mesh-like structure disappeared until 12 weeks of GA and, irrespective of whether a remnant fibrous tissue was present or absent, cartilage tissues became continuous between the occipital and petrosal sides. Until 25 weeks of GA, the inferolateral marginal part of the spheno-occipital junction cartilage extended to the medial junction and attached to the ossified petrosa. The medial junction sometimes contained an irregularly shaped cartilage mass or a woven bone with bone trabeculae, but it was usually attached directly to the bony petrosa without any interruption by calcified cells. In contrast, at the late-term lateral junction, a cartilage mass was sandwiched by bipolar ossification centers on the temporal and occipital bone sides. As the endochondral ossification advances, bones at and around the lateral junction seemed to grow and cover the expanding mastoid air cells. However, the fetal medial junction might grow, in accordance with midline growth at the spheno-occipital junction cartilage. Alternatively, the bony union of these two junctions might establish postnatally.
Branched ends of Reichert's cartilage in the ear: a histological study using human near-term fetuses. 国際誌

Chun-Ai Li, Zhe-Wu Jin, Yohei Honkura, Ai Hirano-Kawamoto, Gen Murakami, Jose Francisco Rodríguez-Vázquez, Yukio Katori

Anatomy & cell biology　2025年2月26日

DOI： 10.5115/acb.24.220 　

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There is little information regarding whether the styloid process "inserts" deeply into the temporal bone petrosa. We examined the involvement of Reichert's cartilage (RC) in the petrosa using sagittal or horizontal histological sections of the heads from 17 near-term fetuses (25-40 weeks). The cranial part of RC usually carried two short branches or protrusions (T-shaped appearance). One of the branches ended in or adjacent to the future tympanic cavity, while another branch ended near the facial nerve canal. Near the latter end, a part of the RC was usually fused with the petrosa, but it was rarely separated from the latter. When a bar toward the tympanic cavity was short or absent, RC displayed a reversed J-shaped course near the facial nerve canal and ended at the attachment to the petrosa (3 of 17 specimens). Overall, considerable variations were evident in the shape, length and topographical relation of RC in the ear. Therefore, an intra-otic root of the styloid process, if identified in adults, seemed not to be a simple bar inserting between the tympanic cavity and the vertical portion of the facial nerve canal. Considerable variations in the RC head suggested that the shape was likely to be determined by mechanical loads from the developing petrosa and/or tympanic bone. Those observations were clearly contrast to the degenerating Meckel's cartilage that induces protrusions of the petrosa ant tympanic bone. After birth, endochondral ossification of the petrosa appeared to expand antero-inferiorly to involve all branches of RC.
A mutation in Tmem135 causes progressive sensorineural hearing loss. 国際誌

Mi-Jung Kim, Shion Simms, Ghazaleh Behnammanesh, Wei-Wen Chen, Yohei Honkura, Jun Suzuki, Hyo-Jin Park, Marcus Milani, Yukio Katori, Jonathan E Bird, Akihiro Ikeda, Shinichi Someya

Hearing research　459　109221-109221　2025年2月14日

DOI： 10.1016/j.heares.2025.109221 　

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Transmembrane protein 135 (TMEM135) is a highly conserved 52 kDa protein with five predicted transmembrane domains that colocalizes with mitochondria and peroxisomes. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism across multiple tissues and species; however, its role in the inner ear and auditory system remains unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135FUN025/FUN025 (FUN025) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) thresholds at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing results, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and more modest changes in inner hair cell survival, spiral ganglion neuron density, and stria vascularis integrity in the cochlea. Our results using BaseScope RNA in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, supporting cells, and stria vascularis. Using Volocity software and Costes colocalization analysis, we found that TMEM135 closely colocalizes with mitochondria in hair cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.
Development and growth of fasciae in and around the esophageal hiatus: a histological study using human fetuses. 国際誌

Ai Hirano-Kawamoto, Yohei Honkura, Gen Murakami, Shin-Ichi Abe, Jose Francisco Rodríguez-Vázquez, Yukio Katori

Surgical and radiologic anatomy : SRA　47　(1)　16-16　2024年12月2日

DOI： 10.1007/s00276-024-03517-4 　

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PURPOSE: An entire fascial configuration at the esophageal hiatus might not be demonstrated histologically. According to observations of human fetus histology, the aim of this study was to consider which factor is likely to make the individual variation in adults. METHODS: We observed frontal histological sections containing the esophageal hiatus from 12 midterm fetuses at 12-16 weeks (crown-rump length: CRL, 85-137 mm) and 10 near-term fetuses at 26-30 weeks (CRL, 214-250 mm). RESULTS: At midterm, the transversalis fascia covering the diaphragm turned upward to join the adventitia of the left aspect of the esophagus: thus, the upper leaflet of the phreno-esophageal membrane was established first. A connection between the adventitia and endothoracic fascia (i.e., the upper leaflet of the PEM) was deleyed in the right. At near-term, both the transversalis and endothoracic fasciae often joined the adventitia in the left side but not in the right side. Therefore, fascial development advanced in the left side as well as the inferior side of the hiatus. The foregut-midgut junction, suggested with cytokeratin 5/6 immunostaining, was located in the hiatus. CONCLUSION: Development and growth of the phreno-esophageal membrane showed left/right and superior/inferior differences. The transiently-appeared pleural recess, the upward protruding right crus of diaphragm and, the right liver and adrenal extending upward seemed to disturb the fascial connection to the adventitia in the right and/or superior side. Individual variations in the fascial configuration at the hiatus might occur due to the site-dependent delay of the establishment of structures.
The prevalence and clinical features of MYO7A-related hearing loss including DFNA11, DFNB2 and USH1B

Kizuki Watanabe, Shin Ya Nishio, Shin Ichi Usami, Takumi Kumai, Akihiro Katada, Noriko Ogasawara, Tomoko Shintani, Shin Ya Morita, Norito Takeichi, Shin Ichi Goto, Atsushi Nanba, Akira Sasaki, Yumiko Kobayashi, Yohei Honkura, Mika Adachi, Shunsuke Takai, Kiyoshi Oda, Teruyuki Sato, Takechiyo Yamada, Kazuhiro Shiina, Tsukasa Ito, Chikako Shinkawa, Akiko Amano, Daisuke Kikuchi, Hiroshi Ogawa, Tetsuro Wada, Yuki Hirose, Emiko Noguchi, Nobuko Moriyama, Kouji Ohtsuka, Kentaro Shirai, Rei Sadayasu, Mari Shimada, Hiroshi Suzumura, Tetsuya Tono, Masaomi Motegi, Ikko Mitoh, Hiroe Tada, Kyoko Nagai, Hideaki Sakata, Kotaro Ishikawa, Naohiro Yoshida, Kunio Mizutari, Yoichi Suzuki, Testuo Ikezono, Han Matsuda, Yoshihiro Noguchi, Hidehiko Takeda, Marina Kobayashi, Yuika Sakurai, Genki Hirabayashi, Shouri Tajima, Nobuhiro Nishiyama, Kyoko Shirai, Sachie Kawaguchi, Satoshi Iwasaki, Masahiro Takahashi, Sakiko Furutate, Shin Ichiro Oka, Hiroshi Yoshihashi, Hiroshi Futagawa, Naoki Ohishi, Makoto Hosoya, Yoshiyuki Kawashima, Taku Ito, Ayako Maruyama, Kozo Kumakawa, Takeshi Matsunobu, Naoko Sakuma, Katsutoshi Takahashi, Akinori Kashio, Hiroko Monobe, Yuji Miyoshi, Kumiko Yabuki, Yukiko Seto, Hajime Sano, Naomi Araki, Yasuhiro Arai, Mayuri Okami, Koichiro Wasano, Hiromitsu Hatakeyama, Yasuhiro Isono, Shinya Ohira, Manabu Komori, Shuji Izumi, Michiro Fujisaka, Atsushi Watanabe, Masayuki Okamoto, Yumi Ito, Mari Takahashi, Maiko Miyagawa, Yutaka Takumi, Hidekane Yoshimura, Jun Shinagawa, Hideaki Moteki, Koji Tsukamoto, Aya Ichinose, Natsuko Obara, Bunya Kuza, Natsuki Takada

Scientific Reports　14　(1)　2024年12月

DOI： 10.1038/s41598-024-57415-1 　

eISSN：2045-2322
Nrf2 Deficiency Exacerbates the Decline in Swallowing and Respiratory Muscle Mass and Function in Mice with Aspiration Pneumonia. 国際誌

Hikaru Hashimoto, Tatsuma Okazaki, Yohei Honkura, Yuzhuo Ren, Peerada Ngamsnae, Takuma Hisaoka, Yasutoshi Koshiba, Jun Suzuki, Satoru Ebihara, Yukio Katori

International journal of molecular sciences　25　(21)　2024年11月4日

DOI： 10.3390/ijms252111829 　

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Aspiration pneumonia exacerbates swallowing and respiratory muscle atrophy. It induces respiratory muscle atrophy through three steps: proinflammatory cytokine production, caspase-3 and calpain, and then ubiquitin-proteasome activations. In addition, autophagy induces swallowing muscle atrophy. Nrf2 is the central detoxifying and antioxidant gene whose function in aspiration pneumonia is unclear. We explored the role of Nrf2 in aspiration pneumonia by examining swallowing and respiratory muscle mass and function using wild-type and Nrf2-knockout mice. Pepsin and lipopolysaccharide aspiration challenges caused aspiration pneumonia. The swallowing (digastric muscles) and respiratory (diaphragm) muscles were isolated. Quantitative RT-PCR and Western blotting were used to assess their proteolysis cascade. Pathological and videofluoroscopic examinations evaluated atrophy and swallowing function, respectively. Nrf2-knockouts showed exacerbated aspiration pneumonia compared with wild-types. Nrf2-knockouts exhibited more persistent and intense proinflammatory cytokine elevation than wild-types. In both mice, the challenge activated calpains and caspase-3 in the diaphragm but not in the digastric muscles. The digastric muscles showed extended autophagy activation in Nrf2-knockouts compared to wild-types. The diaphragms exhibited autophagy activation only in Nrf2-knockouts. Nrf2-knockouts showed worsened muscle atrophies and swallowing function compared with wild-types. Thus, activation of Nrf2 may alleviate inflammation, muscle atrophy, and function in aspiration pneumonia, a major health problem for the aging population, and may become a therapeutic target.
水中内視鏡による上半規管裂隙症候群の治療 18例の経験

川村善宣, 本蔵陽平, 池田怜吉, 大島英敏, 野村有理, 高井俊輔, 草野佑典, 小林俊光, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　34回　316-316　2024年10月
出版者・発行元： (一社)日本耳科学会
補聴器装用が抑うつ・不安、聞こえに対する自己評価に与える影響

里奈上畑, 淳鈴木, 梨紗子角田, 俊輔髙井, 朱里澤田, 剛史佐藤, 陽平本蔵, 怜吉池田, 幸夫香取

AUDIOLOGY JAPAN　67　(5)　438-438　2024年9月30日
出版者・発行元： Japan Audiological Society
DOI： 10.4295/audiology.67.438 　

ISSN：0303-8106

eISSN：1883-7301
耳鳴患者における TRT (Tinnitus Retraining Therapy) が不快閾値に与える影響についての検討

俊輔髙井, 淳鈴木, 朱里澤田, 剛史佐藤, 陽平本蔵, 梨紗子角田, 幸夫香取

AUDIOLOGY JAPAN　67　(5)　520-520　2024年9月30日
出版者・発行元： Japan Audiological Society
DOI： 10.4295/audiology.67.520 　

ISSN：0303-8106

eISSN：1883-7301
Striated muscle fiber crossings of the head and neck: a histological study using near-term human fetuses and elderly cadavers 査読有り

Kim JH, Kitamura K, Honkura Y, Murakami G, Abe S

Anatomy & Cell Biology (Online ahead of print)　2024年7月19日

DOI： 10.5115/acb.24.094. 　
A Mutation in Tmem135 Causes Progressive Sensorineural Hearing Loss. 国際誌

Mi-Jung Kim, Shion Simms, Ghazaleh Behnammanesh, Yohei Honkura, Jun Suzuki, Hyo-Jin Park, Marcus Milani, Yukio Katori, Jonathan E Bird, Akihiro Ikeda, Shinichi Someya

bioRxiv : the preprint server for biology　2024年5月9日

DOI： 10.1101/2024.05.09.593414 　

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Transmembrane protein 135 (TMEM135) is a 52 kDa protein with five predicted transmembrane domains that is highly conserved across species. Previous studies have shown that TMEM135 is involved in mitochondrial dynamics, thermogenesis, and lipid metabolism in multiple tissues; however, its role in the inner ear or the auditory system is unknown. We investigated the function of TMEM135 in hearing using wild-type (WT) and Tmem135 FUN025/FUN025 ( FUN025 ) mutant mice on a CBA/CaJ background, a normal-hearing mouse strain. Although FUN025 mice displayed normal auditory brainstem response (ABR) at 1 month, we observed significantly elevated ABR thresholds at 8, 16, and 64 kHz by 3 months, which progressed to profound hearing loss by 12 months. Consistent with our auditory testing, 13-month-old FUN025 mice exhibited a severe loss of outer hair cells and spiral ganglion neurons in the cochlea. Our results using BaseScope in situ hybridization indicate that TMEM135 is expressed in the inner hair cells, outer hair cells, and supporting cells. Together, these results demonstrate that the FUN025 mutation in Tmem135 causes progressive sensorineural hearing loss, and suggest that TMEM135 is crucial for maintaining key cochlear cell types and normal sensory function in the aging cochlea.
自記式問診票を通じた聴覚の自己評価とオージオグラムの比較検討

冨田尚希, 加藤大雅, 佐藤剛史, 内林俊洋, 本蔵陽平, 鈴木淳, 中瀬泰然, 瀧靖之, 香取幸夫

日本老年医学会雑誌　61　(Suppl.)　181-181　2024年5月
出版者・発行元： (一社)日本老年医学会
ISSN：0300-9173
Cochlear aqueduct revisited: A histological study using human fetuses. 国際誌

Kwang Ho Cho, Ji Hyun Kim, Yohei Honkura, Masahito Yamamoto, Gen Murakami, Jose Francisco Rodríguez-Vázquez, Yukio Katori

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft　253　152236-152236　2024年2月26日

DOI： 10.1016/j.aanat.2024.152236 　

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BACKGROUND AND AIM: The cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. METHODS: We examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39-115 mm) and 12 near-term fetuses (CRL, 225-328 mm). RESULTS: A linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9-10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10-12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. CONCLUSION: The CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development.
Fatty acid binding protein type 7 deficiency preserves auditory function in noise-exposed mice. 国際誌

Jun Suzuki, Tomotaka Hemmi, Masamitsu Maekawa, Masahiro Watanabe, Hitoshi Inada, Hiroyuki Ikushima, Tetsuya Oishi, Ryoukichi Ikeda, Yohei Honkura, Yoshiteru Kagawa, Tetsuaki Kawase, Nariyasu Mano, Yuji Owada, Noriko Osumi, Yukio Katori

Scientific reports　13　(1)　21494-21494　2023年12月6日

DOI： 10.1038/s41598-023-48702-4 　

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Fatty acid-binding protein 7 (FABP7) is vital for uptake and trafficking of fatty acids in the nervous system. To investigate the involvement of FABP7 in noise-induced hearing loss (NIHL) pathogenesis, we used Fabp7 knockout (KO) mice generated via CRISPR/Cas9 in the C57BL/6 background. Initial auditory brainstem response (ABR) measurements were conducted at 9 weeks, followed by noise exposure at 10 weeks. Subsequent ABRs were performed 24 h later, with final measurements at 12 weeks. Inner ears were harvested 24 h after noise exposure for RNA sequencing and metabolic analyses. We found no significant differences in initial ABR measurements, but Fabp7 KO mice showed significantly lower thresholds in the final ABR measurements. Hair cell survival was also enhanced in Fabp7 KO mice. RNA sequencing revealed that genes associated with the electron transport chain were upregulated or less impaired in Fabp7 KO mice. Metabolomic analysis revealed various alterations, including decreased glutamate and aspartate in Fabp7 KO mice. In conclusion, FABP7 deficiency mitigates cochlear damage following noise exposure. This protective effect was supported by the changes in gene expression of the electron transport chain, and in several metabolites, including excitotoxic neurotransmitters. Our study highlights the potential therapeutic significance of targeting FABP7 in NIHL.
Topohistology of the cranial nerves <scp>IX</scp>–<scp>XII</scp> at the cranial base and upper parapharyngeal space: A histological study using human fetuses

Kwang Ho Cho, Yohei Honkura, Ji Hyun Kim, Shogo Hayashi, Kei Kitamura, Gen Murakami, Jose Francisco Rodríguez‐Vázquez

The Anatomical Record　2023年11月27日
出版者・発行元： Wiley
DOI： 10.1002/ar.25355 　

ISSN：1932-8486

eISSN：1932-8494

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Abstract The topographical relationships among the lower cranial nerves, internal carotid artery (ICA), and internal jugular vein (IJV) in the upper parapharyngeal neurovascular bundle remain obscure. Thus, details of the anatomy were examined in human fetus histology. We observed the horizontal histological sections from 20 midterm (9–18 weeks) and 12 near‐term (28–40 weeks) fetuses. At the external skull base, the glossopharyngeal nerve crosses the anterior aspect of the IJV to reach the medially located Hyrtl's fissure in the petrous temporal bone. The nerve crossed the anterior aspect of the ICA medially near or below the first cervical nerve root. Below the hypoglossal nerve canal, the accessory nerve crosses the anterior or posterior aspects of the IJV and moves laterally. During the half‐spiral course, the hypoglossal nerve was tightly attached to the posterolateral–anterior aspects of the vagus nerve and surrounded by a common nerve sheath. The glossopharyngeal ganglia sometimes extended inferiorly to the level of the hypoglossal nerve canal but were absent along the inferior course. The inferior vagal ganglion rarely extends above the occipital condyle. The superior cervical sympathetic ganglion occasionally extends above the first cervical nerve root. The IJV (or ICA) descends to the lateral (or medial) margins of the parapharyngeal neurovascular bundle. The glossopharyngeal (or accessory) nerve crosses the ICA (or IJV) to exit the bundle at the base of the skull (or below the hypoglossal nerve canal). The glossopharyngeal and vagus inferior ganglia differ at each site.
Sphenomandibular ligament and degenerating Meckel's cartilage revisited: Sequential variations with temporal bone deformity for ligament attachment in near-term human fetuses. 国際誌

Zhe-Wu Jin, Yohei Honkura, Masahito Yamamoto, Shogo Hayashi, Gen Murakami, Hiroshi Abe, José Francisco Rodríguez-Vázquez

Journal of anatomy　2023年11月21日

DOI： 10.1111/joa.13974 　

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BACKGROUND: The sphenomandibular ligament (SML) is considered to originate from Meckel's cartilage (MC). However, no study has examined how the os goniale contributes to SML development. METHODS: Semiserial histological sections of heads from 18 near-term fetuses at 27-40 weeks of gestation were examined. OBSERVATIONS: The os goniale and the anterior process of the malleus (AP) provided a long, bar-like membranous bone complex that passed through the petrotympanic and tympanosquamosal fissures. Notably, the AP-goniale complex is sometimes elongated inferiorly to join the SML (n = 4 specimens). Along the complex in the bone fissures, a degenerating MC was often present (n = 12). With (n = 6) or without (n = 3) the MC remnant, the tympanic bone (TYB) protruded inferomedially near the tympanosquamosal fissure, and it sometimes continued to a cartilaginous SML (n = 3). The temporal bone squamosa or petrosa provided a similar bony process approaching the SML. The middle meningeal artery often ran between the sphenoid and petrosa. CONCLUSIONS: Most of the specimens (n = 15) exhibited a sequential change from a cartilaginous SML as a continuation of the MC remnant to the ligament after the disappearance of the cartilage. The degenerating MC appeared to cause transformation from the AP-goniale complex and/or TYB to "another ligament" that replaced the usual SML at the upper part. Near the MC remnant, a similar transformation was also suggested on the squamosa or petrosa. The sphenoid spine appeared to originate often from the sphenoid ala major but sometimes from the TYB.
若年者における音楽聴取習慣と聴覚機能に関する検討

石田智靖, 鈴木淳, 大石哲也, 佐藤剛史, 本蔵陽平, 池田怜吉, 香取幸夫

Audiology Japan　66　(5)　460-460　2023年9月
出版者・発行元： (一社)日本聴覚医学会
ISSN：0303-8106

eISSN：1883-7301
若年者における音楽聴取習慣と聴覚機能に関する検討

石田智靖, 鈴木淳, 大石哲也, 佐藤剛史, 本蔵陽平, 池田怜吉, 香取幸夫

Audiology Japan　66　(5)　460-460　2023年9月
出版者・発行元： (一社)日本聴覚医学会
ISSN：0303-8106

eISSN：1883-7301
HDR syndrome, detected in the neonatal period by newborn hearing screening. 国際誌

Shunsuke Takai, Mika Adachi, Hiyori Takahashi, Masayuki Shirakura, Yohei Honkura, Daisuke Yamauchi, Yukio Katori

Auris, nasus, larynx　2023年8月26日

DOI： 10.1016/j.anl.2023.08.007 　

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Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. Because HDR syndrome is caused by haploinsufficiency in GATA3, it exhibits variation in the onset and progression of hearing loss. In previous reports, the automated auditory brainstem response (AABR) was considered insufficient to detect sensorineural hearing loss caused by HDR syndrome. We report a case of HDR syndrome whose congenital hearing loss was detected by newborn hearing screening (NHS) using AABR. In this case, HDR syndrome was suspected due to hearing loss, hypocalcemia, and her family history. Genetic testing confirmed the diagnosis of HDR syndrome at 5 months of age. Because the phenotype of hearing loss due to HDR syndrome is variable and includes progressive hearing loss, these cases may not be detected by the HNS. However, most of the previous reports were published before the NHS became common and given the frequency of hearing loss complications in HDR syndrome. We consider that there is a reasonable number of HDR syndrome cases with abnormalities on the NHS. We believe that the NHS may also be useful for early detection of hearing loss due to HDR syndrome.
Long-term voice evaluation after arytenoid adduction surgery in patients with unilateral vocal fold paralysis. 国際誌

Kenichi Watanabe, Ai Hirano, Yuta Kobayashi, Takeshi Sato, Yohei Honkura, Yukio Katori

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery　2023年8月16日

DOI： 10.1007/s00405-023-08165-9 　

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PURPOSE: Laryngeal framework surgery, including medialization laryngoplasty and arytenoid adduction (AA), is expected to have a lasting or permanent effect in patients with unilateral vocal fold paralysis (UVFP); however, there are few reports about the long-term outcomes of AA. This study aimed to evaluate the long-term postoperative effects of AA surgery and examine its stability and reliability. METHODS: This study collected the voice handicap index (VHI) questionnaire from patients with UVFP who underwent AA more than 2 years previously. The VHI values preoperatively and 3 months postoperatively (early postoperative evaluation) were retrospectively calculated, and VHI values more than 2 years after surgery (late postoperative evaluation) were collected by mailing a sheet to the patients and asking to fill and return it. Possible influenced subscales such as age, sex, causes of UVFP, affected side, and surgeons were also analyzed. RESULTS: A total of 77 patients with UVFP who underwent AA had significantly lower early and late postoperative evaluations than preoperative evaluations. In 38 patients with no missing values, there were no significant differences between early and late postoperative evaluations, measured at a median of approximately 5 years. There were also no significant differences between early and late postoperative evaluations in any of the subscale groups. CONCLUSION: Patients with UVFP who underwent AA surgery achieved stable voice improvement in the long term after surgery.
Anatomy and function of the lymphatic vessels in the parietal pleura and their plasticity under inflammation in mice. 国際誌

Yuzhuo Ren, Tatsuma Okazaki, Peerada Ngamsnae, Hikaru Hashimoto, Ryoukichi Ikeda, Yohei Honkura, Jun Suzuki, Shin-Ichi Izumi

Microvascular research　148　104546-104546　2023年7月

DOI： 10.1016/j.mvr.2023.104546 　

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Inflammatory pleuritis often causes pleural effusions, which are drained through lymphatic vessels (lymphatics) in the parietal pleura. The distribution of button- and zipper-like endothelial junctions can identify the subtypes of lymphatics, the initial, pre-collecting, and collecting lymphatics. Vascular endothelial growth factor receptor (VEGFR)-3 and its ligands VEGF-C/D are crucial lymphangiogenic factors. Currently, in the pleura covering the chest walls, the anatomy of the lymphatics and connecting networks of blood vessels are incompletely understood. Moreover, their pathological and functional plasticity under inflammation and the effects of VEGFR inhibition are unclear. This study aimed to learn the above-unanswered questions and immunostained mouse chest walls as whole-mount specimens. Confocal microscopic images and their 3-dimensional reconstruction analyzed the vasculatures. Repeated intra-pleural cavity lipopolysaccharide challenge induced pleuritis, which was also treated with VEGFR inhibition. Levels of vascular-related factors were evaluated by quantitative real-time polymerase chain reaction. We observed the initial lymphatics in the intercostals, collecting lymphatics under the ribs, and pre-collecting lymphatics connecting both. Arteries branched into capillaries and gathered into veins from the cranial to the caudal side. Lymphatics and blood vessels were in different layers with an adjacent distribution of the lymphatic layer to the pleural cavity. Inflammatory pleuritis elevated expression levels of VEGF-C/D and angiopoietin-2, induced lymphangiogenesis and blood vessel remodeling, and disorganized the lymphatic structures and subtypes. The disorganized lymphatics showed large sheet-like structures with many branches and holes inside. Such lymphatics were abundant in zipper-like endothelial junctions with some button-like junctions. The blood vessels were tortuous and had various diameters and complex networks. Stratified layers of lymphatics and blood vessels were disorganized, with impaired drainage function. VEGFR inhibition partially maintained their structures and drainage function. These findings demonstrate anatomy and pathological changes of the vasculatures in the parietal pleura and their potential as a novel therapeutic target.
Characteristic findings in the human fetus vestibule: A human temporal bone study. 国際誌

Yohei Honkura, Yukio Katori, Ai Hirano-Kawamoto, Tetsuaki Kawase, Jose Francisco Rodríguez-Vázquez, Gen Murakami, Hiroshi Abe

Auris, nasus, larynx　2023年6月10日

DOI： 10.1016/j.anl.2023.05.004 　

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OBJECTIVE: The "collapse," a highly flexed, dented, or caved membrane between the endo- and peri-lymph of the saccule and utricle in adults, is considered as a morphological aspect of Ménière's syndrome. Likewise, when mesh-like tissues in the perilymphatic space are damaged or lost, the endothelium loses mechanical support and causes nerve irritation. However, these morphologies were not examined in fetuses. METHODS: By using histological sections from 25 human fetuses (crown-rump length[CRL] 82-372 mm; approximately 12-40 weeks), morphologies of the perilymphatic-endolymphatic border membrane and the mesh-like tissue around the endothelium were examined. RESULTS: The highly flexed or caved membrane between the endo- and peri-lymphatic spaces was usually seen in the growing saccule and utricle of fetuses, especially at junctions between the utricle and ampulla at midterm. Likewise, the perilymphatic space around the saccule, utricle and semicircular ducts often lost the mesh-like tissues. The residual mesh-like tissue supported the veins, especially in the semicircular canal. CONCLUSION: Within a cartilaginous or bony room showing a limited growth in size but containing increased perilymph, the growing endothelium appeared to become wavy. Owing to a difference in growth rates between the utricle and semicircular duct, the dentation tended to be more frequently seen at junctions than at free margins of the utricle. The difference in site and gestational age suggested that the deformity was not "pathological" but occurred due to unbalanced growth of the border membrane. Nevertheless, the possibility that the deformed membrane in fetuses was an artifact caused by delayed fixation is not deniable.
Transient connection between the vestibular aqueduct and utricle: a study using sagittal sections of human embryonic heads. 国際誌

Yohei Honkura, Yukio Katori, Ai Hirano-Kawamoto, Tetsuaki Kawase, Jose Francisco Rodríguez-Vázquez, Gen Murakami, Hiroshi Abe

Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft　250　152113-152113　2023年6月8日

DOI： 10.1016/j.aanat.2023.152113 　

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BACKGROUND: The aqeductus vestibuli (aqueduct) is believed to connect to the saccule in embryos and adults. However, in embryos, the saccule and utricle are known to communicate widely to provide a common endolymph space "atrium". METHODS: Using sagittal histological sections from five embryos (crown-rump length or CRL, 14-21mm), nine early fetuses (CRL 24-35mm) and 12 midterm and near-term fetuses (CRL 82-272mm), we revisited the development and growth of the human ear aqueduct. RESULTS: The atrium took on a thick tube-like appearance as an antero-inferior continuation of the aqueduct, but soon divided into multiple gulfs. Most of the gulfs corresponded to the ampullae of semicircular ducts, while one gulf at the antero-medio-inferior corner corresponded to the future saccule. Notably, in eight of the 14 embryos and early fetuses, the aqueduct ended at the utricle near the primitive ampulla of the anterior (superior) or posterior semicircular duct. Conversely, an embryo of CRL 21mm was the smallest specimen in which the aqueduct joined the gulf-like saccule. At midterm and near-term, the growing perilymph space separated the aqueduct from the utricle and appeared to push the aqueduct toward the saccule. A topographical change occurred between the embryonic superiorly located utricle and the inferiorly-located saccule to create the antero-posterior arrangement in adults. CONCLUSIONS: Consequently, the vestibular end of the aqueduct was most likely to migrate anteriorly from the utricle to the saccule at 6-8 weeks possibly due to differential growth of the endothelium. Previous reconstructions of the embryonic aqueduct might be biased by the adult morphology.
Examination of Factors Affecting the Likelihood of Whether Individuals Would Purchase Cartilage Conduction Hearing Aids. 国際誌

Shunsuke Takai, Takeshi Sato, Yuya Miyakura, Mika Adachi, Yohei Honkura, Daisuke Yamauchi, Yukio Katori

Audiology research　13　(3)　347-356　2023年5月11日

DOI： 10.3390/audiolres13030030 　

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Cartilage conduction hearing aids (CC-HAs) are a novel type of hearing aid relying on cartilage conduction, the so-called third auditory conduction pathway. However, CC-HAs have only recently entered routine clinical use, and therefore data on their usefulness are lacking. The purpose of this study was to examine the possibility of assessing whether individual patients would show good adaptation to CC-HAs. Thirty-three subjects (41 ears in total) underwent a free trial of CC-HAs. Age, disease category, and the pure-tone threshold of air and bone conduction, unaided field sound threshold, aided field sound threshold, and functional gain (FG) at 0.25, 0.5, 1, 2, and 4 kHz were compared between patients who subsequently purchased and did not purchase the CC-HAs. Overall, 65.9% of the subjects purchased CC-HAs after the trial. In comparison to non-purchasers, those who decided to purchase CC-HAs showed better pure tone hearing thresholds at high frequencies for both air conduction (2 and 4 kHz) and bone conduction (1, 2, and 4 kHz), as well as for aided thresholds in the sound field (1, 2, and 4 kHz) when using CC-HAs. Therefore, the high-frequency hearing thresholds of subjects trialing CC-HAs might be helpful for identifying those who are likely to benefit from them.
Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Tomotaka Hemmi, Jun Suzuki, Yoshiteru Kagawa, Yohei Honkura, Ryoukichi Ikeda, Ken Hashimoto, Chitose Suzuki, Tetsuaki Kawase, Takaaki Abe, Yuji Owada, Yukio Katori

The Tohoku journal of experimental medicine　2023年4月20日

DOI： 10.1620/tjem.2023.J031 　
Nasal capsule ossification: A histological study using human foetuses to find an association between the foetus and adult morphologies of the nasal wall 国際誌国際共著査読有り

Masahito Yamamoto, Shogo Hayashi, Yohei Honkura, Ai Hirano‐Kawamoto, Yukio Katori, Gen Murakami, José Francisco Rodríguez‐Vázquez, Shinichi Abe

Journal of Anatomy　243　(3)　517-533　2023年3月30日
出版者・発行元： Wiley
DOI： 10.1111/joa.13867 　

ISSN：0021-8782

eISSN：1469-7580

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Recent molecular biology studies have revealed the process of nasal capsule determination. We aimed to create a fate map showing the association between the adult and embryonic components of the nasal wall and nasal capsule derivatives. We examined paraffin-embedded histological sections between 15 mid-term (9–16 weeks) and 12 near-term (27–40 weeks) foetuses. Until 15 weeks, membranous ossification occurred ‘along’ the capsular cartilage, contributing to the formation of the vomer, maxilla and bony nasal septum as well as the nasal, frontal and lacrimal bones. After 15 weeks, a wide lateral part of the capsule became thin and fragmented, and degenerative cartilage was observed near the lacrimal bone, in the three conchae, and at the inferolateral end of the capsule sandwiched between the maxilla and palatine bone. The disappearing cartilages appeared to be replaced by nearby membranous bones. This type of membranous ossification did not appear to use the capsular cartilage as a ‘mould’, although the perichondrium may have a role in inducing ossification. Calcified cartilage indicated endochondral ossification in the inferior concha until 15 weeks and, later, at the bases of three conchae and around the future sphenoid sinus (i.e. the concha sphenoidalis). The capsular cartilage extended antero-superiorly over the frontal bone and inserted into the nasal bone. At 40 weeks, the capsular cartilage remained in the cribriform plate and at the inferolateral end along the palatine bone. Consequently, less guidance from the nasal capsule seemed to provide great individual variation in the shape of the wide anterolateral wall of the nasal cavity.
[Secondary Publication] 本邦の嚥下障害患者における,咽喉頭感覚評価法に関するアンケート調査

神林友紀, 加藤健吾, 池田怜吉, 鈴木淳, 本藏陽平, 平野愛, 太田淳, 加賀谷斉, 井上誠, 兵頭政光, 大森孝一, 末廣篤, 岡崎達馬, 出江紳一, 小山重人, 佐々木啓一, 熊井良彦, 二藤隆春, 栗山進一, 小川武則, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　126　(3)　243-244　2023年3月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN：2436-5793

eISSN：2436-5866
[Secondary Publication] 本邦の嚥下障害患者における,咽喉頭感覚評価法に関するアンケート調査

神林友紀, 加藤健吾, 池田怜吉, 鈴木淳, 本藏陽平, 平野愛, 太田淳, 加賀谷斉, 井上誠, 兵頭政光, 大森孝一, 末廣篤, 岡崎達馬, 出江紳一, 小山重人, 佐々木啓一, 熊井良彦, 二藤隆春, 栗山進一, 小川武則, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　126　(3)　243-244　2023年3月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN：2436-5793

eISSN：2436-5866
Sex differences in body composition, voluntary wheel running activity, balance performance, and auditory function in CBA/CaJ mice across the lifespan. 国際誌

Mi-Jung Kim, Peter B Carmichael, Upal Bose, Yohei Honkura, Jun Suzuki, Dalian Ding, Samantha L Erfe, Shion S Simms, Kishan A Avaiya, Marcus N Milani, Elizabeth J Rymer, Daniella T Fragnito, Nathan Strom, Richard Salvi, Shinichi Someya

Hearing research　428　108684-108684　2022年12月27日

DOI： 10.1016/j.heares.2022.108684 　

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Hearing loss is the third most prevalent chronic health condition affecting older adults and age-related hearing loss (ARHL) is the most common form of hearing impairment. Significant sex differences in hearing have been documented in humans and rodents. In general, the results of these studies show that men lose their hearing more rapidly than women. However, the cellular mechanism underlying sex differences in hearing or hearing loss remains largely unknown, and to our knowledge, there is no well-established animal model for studying sex differences in hearing. In the current study, we examined sex differences in body composition, voluntary wheel running activity, balance performance, auditory function, and cochlear histology in young, middle-age, and old CBA/CaJ mice, a model of age-related hearing loss. As expected, body weight of young females was lower than that of males. Similarly, lean mass and total water mass of young, middle-age, and old females were lower than those of males. Young females showed higher voluntary wheel running activity during the dark cycle, an indicator of mobility, physical activity, and balance status, compared to males. Young females also displayed higher auditory brainstem response (ABR) wave I amplitudes at 8 kHz, wave II, III, V amplitudes at 8 and 48 kHz, and wave IV/I and V/I amplitude ratios at 48 kHz compared to males. Collectively, our findings suggest that the CBA/CaJ mouse strain is a useful model to study the cellular mechanisms underlying sex differences in physical activity and hearing.
Anatomy and pathology of lymphatic vessels under physiological and inflammatory conditions in the mouse diaphragm. 国際誌

Peerada Ngamsnae, Tatsuma Okazaki, Yuzhou Ren, Yunxiang Xia, Hikaru Hashimoto, Ryoukichi Ikeda, Yohei Honkura, Yukio Katori, Shin-Ichi Izumi

Microvascular research　145　104438-104438　2022年9月16日

DOI： 10.1016/j.mvr.2022.104438 　

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The lymphatic vessels in the parietal pleura drain fluids. Impaired drainage function and excessive fluid entry in the pleural cavity accumulate effusion. The rat diaphragmatic lymphatics drain fluids from the pleura to the muscle layer. Lymphatic subtypes are characterized by the major distribution of discontinuous button-like endothelial junctions (buttons) in initial lymphatics and continuous zipper-like junctions (zippers) in the collecting lymphatics. Inflammation replaced buttons with zippers in tracheal lymphatics. In the mouse diaphragm, the structural relationship between the lymphatics and blood vessels, the presence of lymphatics in the muscle layer, and the distributions of initial and collecting lymphatics are unclear. Moreover, the endothelial junctional alterations and effects of vascular endothelial growth factor receptor (VEGFR) inhibition under pleural inflammation are unclear. We subjected the whole-mount mouse diaphragms to immunohistochemistry. The lymphatics and blood vessels were distributed in different layers of the pleural membrane. Major lymphatic subtypes were initial lymphatics in the pleura and collecting lymphatics in the muscle layer. Chronic pleural inflammation disorganized the stratified layers of the lymphatics and blood vessels and replaced buttons with zippers in the pleural lymphatics, which impaired drainage function. VEGFR inhibition under inflammation maintained the vascular structures and drainage function. In addition, VEGFR inhibition maintained the lymphatic endothelial junctions and reduced the blood vessel permeability under inflammation. These findings may provide new targets for managing pleural effusions caused by inflammation, such as pleuritis and empyema, which are common pneumonia comorbidities.
脂肪酸結合タンパク質7型(Fabp7)の欠損が騒音曝露後の聴覚機能に与える影響

鈴木淳, 池田怜吉, 本蔵陽平, 川瀬哲明, 香取幸夫

Audiology Japan　65　(5)　316-316　2022年9月
出版者・発行元： (一社)日本聴覚医学会
ISSN：0303-8106

eISSN：1883-7301
高齢者総合機能評価に適した聴覚スクリーニング測定用アプリケーションの開発

冨田尚希, 佐藤剛史, 本蔵陽平, 鈴木淳, 香取幸夫, 瀧靖之

日本老年医学会雑誌　59　(Suppl.)　116-116　2022年5月
出版者・発行元： (一社)日本老年医学会
ISSN：0300-9173
高齢者総合機能評価に適した聴覚スクリーニング測定用アプリケーションの開発

冨田尚希, 佐藤剛史, 本蔵陽平, 鈴木淳, 香取幸夫, 瀧靖之

日本老年医学会雑誌　59　(Suppl.)　116-116　2022年5月
出版者・発行元： (一社)日本老年医学会
ISSN：0300-9173
A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants.

Kinuko Ohneda, Masahiro Hiratsuka, Hiroshi Kawame, Fuji Nagami, Yoichi Suzuki, Kichiya Suzuki, Akira Uruno, Mika Sakurai-Yageta, Yohei Hamanaka, Makiko Taira, Soichi Ogishima, Shinichi Kuriyama, Atsushi Hozawa, Hiroaki Tomita, Naoko Minegishi, Junichi Sugawara, Inaho Danjoh, Tomohiro Nakamura, Tomoko Kobayashi, Yumi Yamaguchi-Kabata, Shu Tadaka, Taku Obara, Eiji Hishimuma, Nariyasu Mano, Masaki Matsuura, Yuji Sato, Masateru Nakasone, Yohei Honkura, Jun Suzuki, Yukio Katori, Yoichi Kakuta, Atsushi Masamune, Yoko Aoki, Masaharu Nakayama, Shigeo Kure, Kengo Kinoshita, Nobuo Fuse, Masayuki Yamamoto

JMA journal　5　(2)　177-189　2022年4月15日

DOI： 10.31662/jmaj.2021-0156 　

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Introduction: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings. Methods: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1, CYP2C19, and NUDT15, were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants' understanding of the topic, psychological impact, and attitude toward the study. Results: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable. Conclusions: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.
Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan. 国際誌

Yoh-Ichiro Iwasa, Shin-Ya Nishio, Hidekane Yoshimura, Akiko Sugaya, Yuko Kataoka, Yukihide Maeda, Yukihiko Kanda, Kyoko Nagai, Yasushi Naito, Hiroshi Yamazaki, Tetsuo Ikezono, Han Matsuda, Masako Nakai, Risa Tona, Yuika Sakurai, Remi Motegi, Hidehiko Takeda, Marina Kobayashi, Chiharu Kihara, Takashi Ishino, Shin-Ya Morita, Satoshi Iwasaki, Masahiro Takahashi, Sakiko Furutate, Shin-Ichiro Oka, Toshinori Kubota, Yasuhiro Arai, Yumiko Kobayashi, Daisuke Kikuchi, Tomoko Shintani, Noriko Ogasawara, Yohei Honkura, Shuji Izumi, Misako Hyogo, Yuzuru Ninoyu, Mayumi Suematsu, Jun Nakayama, Nana Tsuchihashi, Mayuri Okami, Hideaki Sakata, Hiroshi Yoshihashi, Taisuke Kobayashi, Kozo Kumakawa, Tadao Yoshida, Tomoko Esaki, Shin-Ichi Usami

Human genetics　141　(3-4)　865-875　2022年4月

DOI： 10.1007/s00439-021-02351-7 　

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Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.
Correction to: Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan. 国際誌

Yoh-Ichiro Iwasa, Shin-Ya Nishio, Hidekane Yoshimura, Akiko Sugaya, Yuko Kataoka, Yukihide Maeda, Yukihiko Kanda, Kyoko Nagai, Yasushi Naito, Hiroshi Yamazaki, Tetsuo Ikezono, Han Matsuda, Masako Nakai, Risa Tona, Yuika Sakurai, Remi Motegi, Hidehiko Takeda, Marina Kobayashi, Chiharu Kihara, Takashi Ishino, Shin-Ya Morita, Satoshi Iwasaki, Masahiro Takahashi, Sakiko Furutate, Shin-Ichiro Oka, Toshinori Kubota, Yasuhiro Arai, Yumiko Kobayashi, Daisuke Kikuchi, Tomoko Shintani, Noriko Ogasawara, Yohei Honkura, Shuji Izumi, Misako Hyogo, Yuzuru Ninoyu, Mayumi Suematsu, Jun Nakayama, Nana Tsuchihashi, Mayuri Okami, Hideaki Sakata, Hiroshi Yoshihashi, Taisuke Kobayashi, Kozo Kumakawa, Tadao Yoshida, Tomoko Esaki, Shin-Ichi Usami

Human genetics　141　(3-4)　993-995　2022年4月

DOI： 10.1007/s00439-021-02392-y 　
嚥下性肺炎の重症化予防における、転写因子Nrf2の機能の解析

橋本光, 岡崎達馬, 本蔵陽平, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　125　(4)　725-725　2022年4月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN：2436-5793

eISSN：2436-5866
Ndufs4の欠失が音響曝露後の聴覚に及ぼす影響

逸見朋隆, 鈴木淳, 本藏陽平, 池田怜吉, 橋本研, 川瀬哲明, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　125　(4)　730-730　2022年4月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN：2436-5793

eISSN：2436-5866
喉頭枠組み手術を行う片側性声帯麻痺患者の発話検査

香取幸夫, 佐藤剛史, 平野愛, 本藏陽平, 渡邊健一

日本気管食道科学会会報　73　(2)　s10-s10　2022年4月
出版者・発行元： (NPO)日本気管食道科学会
ISSN：0029-0645

eISSN：1880-6848
Fetal development and growth of the fissula ante fenestram in the human ear. 国際誌

José Francisco Rodríguez-Vázquez, María Cruz Iglesias-Moreno, Adriana Poch, Gen Murakami, Hiroshi Abe, Yohei Honkura

Anatomical record (Hoboken, N.J. : 2007)　305　(2)　424-435　2022年2月

DOI： 10.1002/ar.24711 　

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Since the fissula ante fenestram (FAF) is considered as a focus of otosclerotic lesion and a route of perilymph leakage, there are few description of prenatal development of the cartilaginous canal passing though the cochlear wall. We examined the sagittal and frontal histological sections of the ear from 32 human fetuses at 8-37 weeks of gestational age. At 8-12 weeks, in the immediately anterior side of a connection between the cochlear and canalicular parts of the otic capsule cartilage, the FAF appeared as a tear of a cartilage between the basal and second turns of the cochlea. The tear became a slit opening to the scala vestibuli. At 13-15 weeks, the FAF, less than 1.2 mm in length, had the anterosuperior and postero-inferior apertures: the former was near the geniculate ganglion and became closed after 15 weeks, while the latter approached the oval window. Third trimester fetuses, the FAF, 1.5-2.0 mm in length, consistently carried a single, postero-inferior aperture extending along the anterior margin of the oval window and it contained no definite epithelium and vessel. Although it was endochondral ossification, there was no clear zonation in cartilage cells of the FAF. A mechanical stress during three-dimensional coiling of the cochlear ducts seemed to provide the FAF. After the FAF was established, the stapes footplate might use a part of the inferior aperture for the syndesmosis. A specific ossification was seen in the FAF, but it might rarely cause the pathological syndesmosis.
Malignant otitis externa presenting cerebral infarction from pseudoaneurysm: A case report and a review of the literature. 国際誌

Yasutoshi Koshiba, Ryoukichi Ikeda, Jun Suzuki, Yohei Honkura, Yukino Funayama, Kensuke Ikeda, Hitoshi Warita, Masashi Aoki, Tetsuaki Kawase, Yukio Katori

Clinical case reports　10　(2)　e05276　2022年2月

DOI： 10.1002/ccr3.5276 　

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Chronic renal failure and diabetes mellitus could also be risk factors of pseudoaneurysm of the internal carotid artery (ICA) due to malignant otitis externa (MOE). Although pseudoaneurysm of the ICA is a rarely encountered disease, it should always be taken into consideration when treating patients of MOE.
良聴耳の半規管手術水中内視鏡下手術の経験

山内大輔, 本藏陽平, 橋本研, 川村善宣, 橋本光, 池田怜吉, 神林友紀, 大石哲也, 小林俊光, 大島英敏, 草野佑典, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　31回　177-177　2021年10月
出版者・発行元： (一社)日本耳科学会
片側性声帯麻痺患者の喉頭枠組み術前後での発話音声機能を評価するための音読課題と評価指標に関する検討

佐藤剛史, 苅安誠, 渡邊健一, 本蔵陽平, 平野愛, 鹿島和孝, 香取幸夫

音声言語医学　62　(4)　305-313　2021年10月
出版者・発行元：日本音声言語医学会
ISSN：0030-2813

eISSN：1884-3646
良聴耳の半規管手術水中内視鏡下手術の経験

山内大輔, 本藏陽平, 橋本研, 川村善宣, 橋本光, 池田怜吉, 神林友紀, 大石哲也, 小林俊光, 大島英敏, 草野佑典, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　31回　177-177　2021年10月
出版者・発行元： (一社)日本耳科学会
片側性声帯麻痺患者に対しての発話評価の意義文章音読課題による休止区間の頻度と時間的解析での術前後比較

佐藤剛史, 苅安誠, 本蔵陽平, 平野愛, 鹿島和孝, 渡邊健一, 香取幸夫

言語聴覚研究　18　(3)　170-170　2021年9月
出版者・発行元： (一社)日本言語聴覚士協会
ISSN：1349-5828
Buried oropharyngeal metal mesh foreign bodies in an infant

Shotaro Koizumi, Jun Suzuki, Yohei Honkura, Kenichi Watanabe, Yukio Katori

Otolaryngology Case Reports　20　2021年9月

DOI： 10.1016/j.xocr.2021.100317 　

eISSN：2468-5488
Fetal development of the carotid canal with special reference to a contribution of the sphenoid bone and pharyngotympanic tube. 国際誌

Yohei Honkura, Masahito Yamamoto, José Francisco Rodríguez-Vázquez, Gen Murakam, Hiroshi Abe, Shin-Ichi Abe, Yukio Katori

Anatomy & cell biology　54　(2)　259-269　2021年6月30日

DOI： 10.5115/acb.20.310 　

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The bony carotid canal is a tube-like bone with a rough surface in contrast to smooth surfaces of the other parts of the temporal bone petrosal portion (petrosa): it takes an impression of the additional, out-sourcing product. No study had been conducted to evaluate a contribution of the adjacent sphenoid and pharyngotympanic tube (PTT) to the carotid canal. We examined sagittal and horizontal histological sections of hemi-heads from 37 human fetuses at 10 to 37 weeks. At 10 to 18 weeks, the future carotid canal was identified as a wide loose space between the cartilaginous cochlea and the ossified or cartilaginous sphenoid elements (ala temporalis and pterygoid). A linear mesenchymal condensation extending between the cochlear wall and ala temporalis suggested the future antero-inferior margin of the carotid canal. This delineation was more clearly identified in later stages. After 25 weeks, 1) the growing pterygoid pushed the PTT upward and, in turn, the PTT pushed the internal carotid artery (ICA) upward toward the petrosa: 2) a membranous ossification occurs in the dense mesenchymal tissue, the latter of which took an appearance of an anterior process of the petrosa; 3) the bony process of the petrosa involved the ICA inside or posteriorly. The bony carotid canal was made with membranous ossification in the dense mesenchymal tissue between the petrosa and sphenoid. The mother tissue was detached from the sphenoid by the PTT. The ossification of the septum between the ICA and tympanic cavity seemed to continue after birth.
Underwater Endoscopic Ear Surgery for Closure of Cholesteatomatous Labyrinthine Fistula With Preservation of Auditory Function 国際誌

Daisuke Yamauchi, Yohei Honkura, Yoshinobu Kawamura, Yuichi Shimizu, Tomoki Sunose, Yosuke Hara, Jun Ohta, Jun Suzuki, Tetsuaki Kawase, Yukio Katori

Otology & Neurotology　Publish Ahead of Print　(10)　e1669-e1676　2021年6月25日
出版者・発行元： Ovid Technologies (Wolters Kluwer Health)
DOI： 10.1097/mao.0000000000003241 　

ISSN：1531-7129

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OBJECTIVE: To analyze the outcomes of the underwater endoscopic ear surgery (UWEES) technique for closure of cholesteatomatous labyrinthine fistula (LF) with preservation of auditory function. STUDY DESIGN: Retrospective case review study. SETTING: Tertiary referral center. PATIENTS: A total of 12 patients with cholesteatomatous LF. INTERVENTION: Surgical method of closure using UWEES for cholesteatomatous LF to minimize inner ear damage. Artificial cerebrospinal fluid (CSF) was used as the perfusate, except for earlier cases when saline was employed. MAIN OUTCOME MEASURES: Comparison of bone conductance hearing level (BCHL) before and after surgery. A change of BCHL less than 10 dB was defined as successful preservation of bone conductance hearing. RESULTS: All cases of LF were treated successfully by closure using the UWEES technique. Seven cases were type I, one was type IIa, and four were type III according to the Milewski and Dornhoffer classification of LF. The average LF size was 3.1 mm (1-7 mm). Eleven patients were evaluated and their bone conductance hearing was well preserved in all of them (11/11). One patient was too young for preoperative evaluation of BCHL, but hearing preservation was verified 2 years later at the age of 6 years. Remarkably, none of the patients complained of vertigo, except for only a slight manifestation on postoperative day 1. CONCLUSION: The UWEES technique was effective for closure of cholesteatomatous LF with preservation of auditory function.
A Novel Mutation in LMX1B (p.Pro219Ala) Causes Focal Segmental Glomerulosclerosis with Alport Syndrome-like Phenotype.

Yuji Oe, Eikan Mishima, Takayasu Mori, Koji Okamoto, Yohei Honkura, Tasuku Nagasawa, Mai Yoshida, Hiroshi Sato, Jun Suzuki, Ryoukichi Ikeda, Eisei Sohara, Shinichi Uchida, Yukio Katori, Mariko Miyazaki

Internal medicine (Tokyo, Japan)　60　(18)　2991-2996　2021年4月5日

DOI： 10.2169/internalmedicine.6987-20 　

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A 69-year-old woman presented with mild renal dysfunction, proteinuria, and sensorineural hearing loss. A renal biopsy showed focal segmental glomerulosclerosis with thinning of the glomerular basement membrane. There was a positive family history of end-stage kidney disease and hearing loss. Although Alport syndrome was suspected from these features, a genetic test using next-generation sequencer identified a novel missense mutation in LMX1B, c.655C>G: p. (Pro219Ala). In silico analyses predicted the pathogenicity of the mutation. Thus, the present case was diagnosed as LMX1B-associated nephropathy presenting with Alport syndrome-like phenotype, expanding the disease spectrum of LMX1B nephropathy.
Auricular cartilage configuration: a histological study using late‐stage human fetuses and adult cadavers 国際誌

Chiaki Hashimoto, Kei Kitamura, Masahito Yamamoto, Yohei Honkura, Gen Murakami, Hiroshi Abe, Shinichi Abe

The Anatomical Record　304　(12)　2661-2672　2021年2月23日
出版者・発行元： Wiley
DOI： 10.1002/ar.24608 　

ISSN：1932-8486

eISSN：1932-8494

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The auricular cartilage is considered to develop from a funnel-like arrangement of six embryonic hillocks. However, there is little information as to when and how the initial cartilage plate differentiates into the major three hollows or caves: the concha, the scapha and the triangular fossa. We examined semiserial histological sections from 42 human fetuses as well as from seven cadavers of elderly individuals. Tangential sections from adults suggested that three ring-like cartilages were combined to provide a single auricular cartilage and that the external auditory meatus was attached to the lowest ring or concha. All of the fetuses studied carried the three major hollows delineated by skin folds. These skin folds often contained a cartilage loop as a core in place of a thickening or tubercle. Conversely, some of the skin folds corresponded to a highly wavy cartilage plate without looping. According to whether the cartilage loop was present or absent in horizontal sections from 35 fetuses, we classified the cartilage morphology into four patterns, the most frequent of which was absence of the triangular fossa loop (27 fetuses), followed by absence of the scapha loop (11 fetuses). Each pattern was evenly distributed among small and large fetuses. This suggested that some form of cartilage correction or reconstruction was likely to occur after birth, especially at the triangular fossa and/or scapha. Infants appear to show significant region-specific variation in the postnatal growth of the auricular cartilages, especially at the triangular fossa and/or scapha.
Loudness functions for patients with functional hearing loss. 国際誌

Saori Shiraki, Takeshi Sato, Ryoukichi Ikeda, Jun Suzuki, Yohei Honkura, Shuichi Sakamoto, Yukio Katori, Tetsuaki Kawase

International journal of audiology　61　(1)　1-7　2021年2月15日

DOI： 10.1080/14992027.2021.1881627 　

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OBJECTIVES: To compare the loudness functions (loudness ratings as a function of sound level) obtained from patients diagnosed as having functional hearing loss (FHL) with those for patients with sensorineural hearing loss (SNHL) and healthy volunteers. DESIGN: Loudness functions for a 1000 Hz tone for patients with FHL and SNHL were assessed based on the categorical loudness scaling method. The data were compared with control data obtained in our facilities. STUDY SAMPLE: 18 patients (33 ears) with FHL and 10 patients (19 ears) with SNHL. RESULTS: For patients with SNHL and healthy volunteers, loudness increased progressively with increasing sound level above the audiometric threshold, with no exceptions. However, for about 70% of the patients with FHL, a different type of loudness function was obtained; the thresholds determined from the loudness function, which were defined as the minimum sound levels at which loudness could be judged, were 10 dB or more lower than the audiometric threshold (>10 dB), and/or the loudness ratings were elevated for a sound at the audiometric threshold. CONCLUSIONS: The results support the hypothesis that patients with FHL often make threshold judgments based on a certain loudness.
Questionnaire survey on pharyngolaryngeal sensation evaluation regarding dysphagia in Japan 国際誌

Tomonori Kambayashi, Kengo Kato, Ryoukichi Ikeda, Jun Suzuki, Yohei Honkura, Ai Hirano-Kawamoto, Jun Ohta, Hitoshi Kagaya, Makoto Inoue, Masamitsu Hyodo, Koichi Omori, Atsushi Suehiro, Tatsuma Okazaki, Shin-Ichi Izumi, Shigeto Koyama, Keiichi Sasaki, Yoshihiko Kumai, Takaharu Nito, Shinichi Kuriyama, Takenori Ogawa, Yukio Katori

Auris Nasus Larynx　48　(4)　666-671　2021年2月
出版者・発行元： Elsevier BV
DOI： 10.1016/j.anl.2021.01.022 　

ISSN：0385-8146

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OBJECTIVE: The objective is to conduct a questionnaire survey regarding pharyngolaryngeal sensation evaluation in dysphagia to understand the current situation in Japan. METHOD: The questionnaire was sent to the councilor of the Society of Swallowing and Dysphagia of Japan and the Japanese Society of Dysphagia Rehabilitation-Certified Clinician. The prospective questionnaire survey included the questions listed below: Q1: What do you think of the importance of pharyngolaryngeal sensory evaluation? Q2: Select one of the essential swallowing sensations. Q3: Select one of the following regarding the frequency of sensory examination of the larynx. Q4: Select the proportion of cases the sensory test results affect. Q5: As a pharyngolaryngeal sensory evaluation method in swallowing function evaluation, please fill in the table below for the frequency, difficulty, and effectiveness of the following tests, such as gag reflex, touching the larynx by endoscopy, touching the larynx by the probe with endoscopy, cough reflex test, swallowing provocation test. RESULTS: The essential swallowing sensations of mechanical stimulation, chemical stimulation, thermal stimulation were 84.9%, 5.4%, and 9.7%, respectively. The frequency of touching the larynx by endoscopy in the otolaryngology group and cough reflex test in dentistry was significantly higher than the other groups (p < 0.05). The correlation between the frequency and difficulty or effectiveness of the sensory tests indicated that the frequency and difficulty are significantly correlated between each item. CONCLUSION: Our results aid in increasing understanding and selection of pharyngolaryngeal sensation evaluation for dysphagia patients.
Oral reading task with selected indices to evaluate speaking voice function in patients with unilateral vocal fold paralysis before and after surgical interventions

Takeshi Sato, Makoto Kariyasu, Kenichi Watanabe, Yohei Honkura, Ai Hirano, Kazutaka Kashima, Yukio Katori

Japan Journal of Logopedics and Phoniatrics　62　(4)　305-313　2021年
出版者・発行元： Japan Society of Logopedics and Phoniatrics
DOI： 10.5112/JJLP.62.305 　

ISSN：0030-2813
Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss. 国際誌

Tetsuya Oishi, Daisuke Matsumaru, Nao Ota, Hiroshi Kitamura, Tianxiang Zhang, Yohei Honkura, Yukio Katori, Hozumi Motohashi

NPJ aging and mechanisms of disease　6　(1)　14-14　2020年12月14日

DOI： 10.1038/s41514-020-00053-4 　

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Age-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low-mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.
Middle ear adenoma with facial palsy: A case report and a review of the literature: Middle ear adenoma with facial palsy. 国際誌

Tadahisa Shishido, Ryoukichi Ikeda, Jun Suzuki, Yohei Honkura, Yasutoshi Koshiba, Gosuke Watarai, Tomonori Kanbayashi, Masaki Hatano, Daisuke Yamauchi, Tetsuaki Kawase, Yukio Katori

Auris, nasus, larynx　49　(3)　529-533　2020年11月24日

DOI： 10.1016/j.anl.2020.11.003 　

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A 52-year-old man presented to our emergency department with an acute onset of right-sided facial nerve (FN) palsy of House-Brackmann grade V. Electroneurography (ENoG) was conducted with no response at the right FN, as compared with the left FN (0%). We performed a biopsy of the right middle ear mass and histological studies showed the tumor to be neuroendocrine tumors (NET) of the middle ear. We resected the tumor with canal wall down mastoidectomy and reconstructed the posterior meatal wall with soft tissue. Three months after surgery, the FN paralysis had improved with House-Brackmann grade II. We reviewed cases of NET with FN palsy, and nine patients, including our case, have been reported. Our case is the first report of ENoG for the description of FN palsy due to NET. Although the ENoG value was 0%, it was remarkably improved by surgery. The other cases of NET patients with FN palsy also recovered FN function after surgery. These results suggest that it is recommended to perform the total resection of the tumor to improve the FN function.
上半規管裂隙症候群における水中内視鏡下耳科手術による閉塞術の手技と利点

山内大輔, 川村善宣, 本藏陽平, 小林俊光, 池田怜吉, 宮崎浩充, 川瀬哲明, 香取幸夫

Otology Japan　30　(3)　159-166　2020年10月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
乳幼児の咽頭金属異物の2例

小泉祥太郎, 鈴木淳, 渡邊健一, 本藏陽平, 川村善宣, 逸見朋隆, 渡来剛右, 遠藤拓弥, 石垣賢人, 香取幸夫

日本耳鼻咽喉科学会会報　123　(4)　1099-1099　2020年9月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
乳幼児の咽頭金属異物の2例

小泉祥太郎, 鈴木淳, 渡邊健一, 本藏陽平, 川村善宣, 逸見朋隆, 渡来剛右, 遠藤拓弥, 石垣賢人, 香取幸夫

日本耳鼻咽喉科学会会報　123　(4)　1099-1099　2020年9月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
The third vascular route of the inner ear or the canal of Cotugno: Its topographical anatomy, fetal development, and contribution to ossification of the otic capsule cartilage 国際誌査読有り

Yohei Honkura, Shogo Hayashi, Hiroshi Abe, Gen Murakami, Jose F. Rodriguez-Vazquez, Shunichi Shibata

ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY　304　(4)　872-882　2020年9月

DOI： 10.1002/ar.24508 　

ISSN：1932-8486

eISSN：1932-8494
"Passenger gene" problem in transgenic C57BL/6 mice used in hearing research 国際誌査読有り

Jun Suzuki, Hitoshi Inada, Chul Han, Mi-Jung Kim, Ryuichi Kimura, Yusuke Takata, Yohei Honkura, Yuji Owada, Tetsuaki Kawase, Yukio Katori, Shinichi Someya, Noriko Osumi

NEUROSCIENCE RESEARCH　158　6-15　2020年9月

DOI： 10.1016/j.neures.2019.10.007 　

ISSN：0168-0102

eISSN：1872-8111
Characteristics of the Voice Handicap Index for Patients With Unilateral Vocal Fold Paralysis Who Underwent Arytenoid Adduction 国際誌査読有り

Kenichi Watanabe, Takeshi Sato, Yohei Honkura, Ai Kawamoto-Hirano, Kazutaka Kashima, Yukio Katori

JOURNAL OF VOICE　34　(4)　649.e1-649.e6　2020年7月

DOI： 10.1016/j.jvoice.2018.12.012 　

ISSN：0892-1997

eISSN：1873-4588
Morphology of the Upper Esophageal Sphincter or Cricopharyngeus Muscle Revisited A Study Using Adult and Fetal Specimens 国際誌査読有り

Masahito Yamamoto, Keishi Hashimoto, Yohei Honkura, Gen Murakami, Hiroshi Abe, Jose Francisco Rodriguez-Vazquez, Shin-Ichi Abe

CLINICAL ANATOMY　33　(5)　782-794　2020年7月

DOI： 10.1002/ca.23506 　

ISSN：0897-3806

eISSN：1098-2353
Development and growth of auricular cartilage and muscles: A study using human fetuses 国際誌査読有り

Yohei Honkura, Shogo Hayashi, Ji Hyun Kim, Gen Murakami, Hiroshi Abe, José Francisco Rodríguez-Vázquez, Yukio Katori

International Journal of Pediatric Otorhinolaryngology　133　109973-109973　2020年6月

DOI： 10.1016/j.ijporl.2020.109973 　

ISSN：0165-5876

eISSN：1872-8464
Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice 国際誌査読有り

Yohei Honkura, Jun Suzuki, Nobuyuki Sakayori, Hitoshi Inada, Tetsuaki Kawase, Yukio Katori, Noriko Osumi

BMC Research Notes　12　(1)　768-768　2019年11月26日

DOI： 10.1186/s13104-019-4809-8 　

eISSN：1756-0500
内耳における酸化ストレス障害に対する転写因子NRF2の機能の解明

大石哲也, 本蔵陽平, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　466-466　2019年10月
出版者・発行元： (一社)日本耳科学会
当科での軟骨伝導補聴器の装用・評価の報告

宮倉裕也, 山内大輔, 佐藤剛史, 高井俊輔, 本藏陽平, 安達美佳, 白倉真之, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　204-204　2019年10月
出版者・発行元： (一社)日本耳科学会
骨導補聴器の装用が困難であったクルーゾン症候群児に対し、軟骨伝導補聴器で良好な補聴が得られた1例

白倉真之, 安達美佳, 佐藤剛史, 宮倉裕也, 高井俊輔, 本藏陽平, 山内大輔, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　277-277　2019年10月
出版者・発行元： (一社)日本耳科学会
手術的治療にて治癒しえた拍動性耳鳴の2例

池田怜吉, 宮崎浩充, 小林俊光, 本蔵陽平, 川村善宣, 山内大輔

Audiology Japan　62　(5)　517-517　2019年10月
出版者・発行元： (一社)日本聴覚医学会
ISSN：0303-8106

eISSN：1883-7301
Yamauchi法による上半規管裂隙症候群の治療-5症例の経験

川村善宣, 小林俊光, 池田怜吉, 宮崎浩充, 本蔵陽平, 山内大輔, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　352-352　2019年10月
出版者・発行元： (一社)日本耳科学会
当科での軟骨伝導補聴器の装用・評価の報告

宮倉裕也, 山内大輔, 佐藤剛史, 高井俊輔, 本藏陽平, 安達美佳, 白倉真之, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　204-204　2019年10月
出版者・発行元： (一社)日本耳科学会
骨導補聴器の装用が困難であったクルーゾン症候群児に対し、軟骨伝導補聴器で良好な補聴が得られた1例

白倉真之, 安達美佳, 佐藤剛史, 宮倉裕也, 高井俊輔, 本藏陽平, 山内大輔, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　277-277　2019年10月
出版者・発行元： (一社)日本耳科学会
Yamauchi法による上半規管裂隙症候群の治療-5症例の経験

川村善宣, 小林俊光, 池田怜吉, 宮崎浩充, 本蔵陽平, 山内大輔, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　352-352　2019年10月
出版者・発行元： (一社)日本耳科学会
内耳における酸化ストレス障害に対する転写因子NRF2の機能の解明

大石哲也, 本蔵陽平, 川瀬哲明, 香取幸夫

日本耳科学会総会・学術講演会抄録集　29回　466-466　2019年10月
出版者・発行元： (一社)日本耳科学会
Tympanoplasty for adhesive otitis media 査読有り

Daisuke Yamauchi, Yohei Honkura

Otolaryngology - Head and Neck Surgery (Japan)　91　(11)　934-939　2019年10月

ISSN：0914-3491
Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort 国際誌査読有り

Karuna Maekawa, Shin-ya Nishio, Satoko Abe, Shin-ichi Goto, Yohei Honkura, Satoshi Iwasaki, Yukihiko Kanda, Yumiko Kobayashi, Shin-ichiro Oka, Mayuri Okami, Chie Oshikawa, Naoko Sakuma, Hajime Sano, Masayuki Shirakura, Natsumi Uehara, Shin-ichi Usami

GENES　10　(10)　2019年10月

DOI： 10.3390/genes10100735 　

eISSN：2073-4425
The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss 国際誌査読有り

Rika Yasukawa, Hideaki Moteki, Shin-ya Nishio, Kotaro Ishikawa, Satoko Abe, Yohei Honkura, Misako Hyogo, Ryota Mihashi, Tetsuo Ikezono, Tomoko Shintani, Noriko Ogasawara, Kyoko Shirai, Hiroshi Yoshihashi, Takashi Ishino, Koshi Otsuki, Tsukasa Ito, Kazuma Sugahara, Shin-ichi Usami

GENES　10　(10)　2019年10月

DOI： 10.3390/genes10100744 　

eISSN：2073-4425
中耳真珠腫における半規管瘻孔に対する、水中内視鏡下での瘻孔閉鎖術の検討

本蔵陽平, 山内大輔, 清水佑一, 橋本光, 舘田豊, 香取幸夫

日本耳鼻咽喉科学会会報　122　(4)　617-617　2019年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
Complications of using Gore-Tex in medialization laryngoplasty: case series and literature review 国際誌査読有り

Kenichi Watanabe, Ai Hirano, Yohei Honkura, Kazutaka Kashima, Masayuki Shirakura, Yukio Katori

EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY　276　(1)　255-261　2019年1月

DOI： 10.1007/s00405-018-5204-0 　

ISSN：0937-4477

eISSN：1434-4726
Incidence of Functional Nasal Voice in Patients With Patulous Eustachian Tube 国際誌査読有り

Yoko Suzuki, Ryoukichi Ikeda, Hiroshi Hidaka, Hiromitsu Miyazaki, Yohei Honkura, Takeshi Sato, Tetsuaki Kawase, Yukio Katori, Toshimitsu Kobayashi

OTOLOGY & NEUROTOLOGY　39　(10)　E1034-E1038　2018年12月

DOI： 10.1097/MAO.0000000000001981 　

ISSN：1531-7129

eISSN：1537-4505
転写因子NRF2活性化による加齢性難聴予防効果の検討

本蔵陽平, 大石哲也, 川瀬哲明, 香取幸夫

Otology Japan　28　(4)　503-503　2018年9月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
転写因子NRF2の活性化による加齢性難聴予防効果の検討

本蔵陽平, 大石哲也, 川瀬哲明, 香取幸夫

耳鼻咽喉科ニューロサイエンス　32　38-39　2018年5月
出版者・発行元：耳鼻咽喉科ニューロサイエンス研究会
【レドックス疾患学酸素・窒素・硫黄活性種はどう作用するのか、どこまで健康・疾患と関わるのか?】(第2章)レドックスと疾患内耳の酸化障害とその防御機構

本蔵陽平, 香取幸夫

実験医学　36　(5)　827-830　2018年3月
出版者・発行元： (株)羊土社
ISSN：0288-5514
喉頭形成術がもたらす音声障害患者の心理的側面およびQOLへの効果

平野愛, 渡邊健一, 佐藤剛史, 本蔵陽平, 香取幸夫

音声言語医学　59　(1)　52-52　2018年1月
出版者・発行元：日本音声言語医学会
ISSN：0030-2813

eISSN：1884-3646
Tracheostomy using extracorporeal membrane oxygenation in a patient with subglottic stenosis 査読有り

Masayuki Shirakura, Kenichi Watanabe, Hikaru Hashimoto, Youhei Honkura, Eiichi Ishida, Kazuhiro Nomura, Yukio Katori

Journal of Otolaryngology of Japan　121　(11)　1395-1400　2018年

DOI： 10.3950/jibiinkoka.121.1395 　

ISSN：0030-6622
水中内視鏡下操作による経迷路法によって摘出した錐体部真珠腫の3症例

山内大輔, 本蔵陽平, 原陽介, 白倉真之, 日高浩史, 川瀬哲明, 香取幸夫

Otology Japan　27　(4)　474-474　2017年10月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
転写因子NRF2の活性化による酸化ストレスに対する内耳保護効果の解明

本蔵陽平, 大石哲也, 川瀬哲明, 香取幸夫

Otology Japan　27　(4)　550-550　2017年10月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
食道における腸管神経の分布高齢者のご遺体を用いた免疫組織化学的研究

香取幸夫, 本蔵陽平, 平野愛

嚥下医学　6　(2)　261-261　2017年9月
出版者・発行元：日本嚥下医学会
ISSN：2186-3199
疾患・難聴の予防と治療基礎研究の最前線転写因子NRF2の抗酸化作用による内耳保護効果の解明

本蔵陽平, 川瀬哲明, 香取幸夫, 本橋ほづみ

日本抗加齢医学会総会プログラム・抄録集　17回　97-97　2017年6月
出版者・発行元： (一社)日本抗加齢医学会
Enteric neurons of the esophagus: an immunohistochemical study using donated elderly cadavers 国際誌査読有り

Ai Hirano-Kawamoto, Yohei Honkura, Yuta Kobayashi, Gen Murakami, Shin ichi Abe, Yukio Katori

Surgical and Radiologic Anatomy　39　(5)　477-484　2017年5月1日

DOI： 10.1007/s00276-016-1799-2 　

ISSN：0930-1038

eISSN：1279-8517
Morphology and relationships of ultimobranchial body with pharyngeal pouches 査読有り

Masahito Yamamoto, Yohei Honkura, Jose F. Rodriguez-Vazquez, Gen Murakami, Yukio Katori, Shin-ichi Abe

EUROPEAN JOURNAL OF ANATOMY　21　(2)　119-124　2017年4月

ISSN：1136-4890

eISSN：2340-311X
音声障害症例に関するHADSを用いた心理的評価に影響する要因についての検討

佐藤剛史, 渡邊健一, 本蔵陽平, 太田淳, 平野愛, 小林祐太, 香取幸夫

音声言語医学　58　(1)　74-74　2017年1月
出版者・発行元：日本音声言語医学会
ISSN：0030-2813

eISSN：1884-3646
声帯萎縮症における吸入ステロイド薬使用例の検討

渡邊健一, 本蔵陽平, 平野愛, 太田淳, 小林祐太, 佐藤剛史, 香取幸夫

音声言語医学　58　(1)　87-88　2017年1月
出版者・発行元：日本音声言語医学会
ISSN：0030-2813

eISSN：1884-3646
Fetal development of the pulley for muscle insertion tendons: A review and new findings related to the tensor tympani tendon 国際誌査読有り

Jose Francisco Rodríguez-Vázquez, Yohei Honkura, Yukio Katori, Gen Murakami, Hiroshi Abe

Annals of Anatomy　209　1-10　2017年1月1日

DOI： 10.1016/j.aanat.2016.09.001 　

ISSN：0940-9602

eISSN：1618-0402
Nasolacrimal duct opening to the inferior nasal meatus in human fetuses. 査読有り

Yohei Honkura, Yoshitaka Takanashi, Ai Kawamoto-Hirano, Hiroshi Abe, Hajime Osanai, Gen Murakami, Yukio Katori

Okajimas folia anatomica Japonica　94　(3)　101-108　2017年

DOI： 10.2535/ofaj.94.101 　

詳細を見る詳細を閉じる

The purpose of this study is to describe the Hasner's membrane which is the main factor of congenital nasolacrimal duct obstruction. Hasner's membrane at the nasal end of the fetal nasolacrimal duct (NLD) is considered to rupture at and after birth. However, topographical anatomy around the membrane as well as a mechanism of rupture seems to be still obscure. We observed frontal or sagittal sections of 20 late-stage fetuses (28-33 weeks) and found the on-going rupture in 2 specimens. The present sections demonstrated that 1) the nasal dilation was not a simple ball-like structure but extended posteriorly and laterally; 2) dilation of the NLD consistently involved the lacrimal sac; 3) Hasner's membrane and ductal mucosal layer contained no macrophages and no or few arteries and nerves. The posterior extension of the NLD end ranged from 1-2 mm, while the lateral extension 3-5 mm although a site of the thinnest membrane varied in location between specimens. Moreover, the thickest NLD due to dilation was in the slightly orbital or upper side of the nasal end. Therefore, before surgical treatment of Hasner's membrane, evaluation using medical images seems to be necessary. Since the nasal epithelium on Hasner's membrane was most likely to destroy earlier than the NLD mucosal lining, observations of the membrane from the nasal cavity seemed helpful for diagnosis at which site would be broken and when.
Submucosal Elastic Laminae of the Middle and Lower Pharynx: A Histological Study Using Elderly Cadaveric Specimens 国際誌査読有り

Ai Kawamoto-Hirano, Yohei Honkura, Masahito Yamamoto, Shin-ichi Abe, Gen Murakami, Yukio Katori

DYSPHAGIA　31　(5)　635-643　2016年10月

DOI： 10.1007/s00455-016-9721-y 　

ISSN：0179-051X

eISSN：1432-0460
音声障害患者における心理的要因の関連についての検討

佐藤剛史, 渡邊健一, 高梨芳崇, 本蔵陽平, 平野愛, 太田淳, 川瀬哲明, 香取幸夫

言語聴覚研究　13　(3)　147-147　2016年9月
出版者・発行元： (一社)日本言語聴覚士協会
ISSN：1349-5828
水中内視鏡下耳科手術における内視鏡光源による温度上昇の抑制効果について

原陽介, 山内大輔, 本蔵陽平, 日高浩史, 川瀬哲明, 香取幸夫

Otology Japan　26　(4)　470-470　2016年9月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
Cricothyroid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial and Capsular Tissues 国際誌査読有り

Ai Kawamoto, Yohei Honkura, Ryoji Suzuki, Hiroshi Abe, Shin-ichi Abe, Gen Murakami, Yukio Katori

JOURNAL OF VOICE　30　(5)　538-548　2016年9月

DOI： 10.1016/j.jvoice.2015.07.011 　

ISSN：0892-1997

eISSN：1873-4588
Is the ultimobranchial body a reality or myth: A study using serial sections of human embryos 査読有り

Yohei Honkura, Masahito Yamamoto, Toshihito Yoshimoto, Jose Francisco Rodriguez-Vazquez, Gen Murakami, Yukio Katori, Shin Ichi Abe

Okajimas Folia Anatomica Japonica　93　(2)　29-40　2016年8月

DOI： 10.2535/ofaj.93.29 　

ISSN：0030-154X

eISSN：1881-1736
Effect of intratympanic application of efinaconazole 10 % solution in the guinea pig. 国際誌査読有り

Kazuya Arakawa, Kazuhiro Nomura, Hidetoshi Oshima, Yohei Honkura, Ryoukichi Ikeda, Hiroshi Hidaka, Tetsuaki Kawase, Yukio Katori

European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery　273　(5)　1137-42　2016年5月

DOI： 10.1007/s00405-015-3669-7 　

詳細を見る詳細を閉じる

Efinaconazole 10 % solution is a new triazole antifungal agent developed for the topical treatment of fungal infections of the nails. The current study examined the effect of intratympanic application of efinaconazole 10 % solution in the guinea pig ear. Sixteen male Hartley guinea pigs (weight 501-620 g) were divided into 3 groups to be treated with efinaconazole 10 % solution, gentamicin (50 mg/mL), or saline solution. Topical solutions of 0.2 mL were applied through a small hole made at the tympanic bulla once daily for 7 consecutive days. Post-intervention auditory brainstem responses were obtained 7 days after the last treatment. The extent of middle ear damage and hair cell loss was investigated. The efinaconazole- and gentamicin-treated groups showed severe deterioration in auditory brainstem response threshold. Middle ear examination revealed extensive changes in the efinaconazole-treated group and medium changes in the gentamicin-treated group. Hair cells were preserved in the efinaconazole- and saline-treated groups, but severe damage was seen in the gentamicin group. In conclusion, efinaconazole 10 % solution applied intratympanically to the guinea pig middle ear caused significant middle ear inflammation and hearing impairment.
Switching of the Laryngeal Cavity From the Respiratory Diverticulum to the Vestibular Recess: A Study Using Serial Sagittal Sections of Human Embryos and Fetuses 国際誌査読有り

Masahito Yamamoto, Yohei Honkura, Jose Francisco Rodriguez-Vazquez, Gen Murakami, Yukio Katori, Baik Hwan Cho, Shin-ichi Abe

JOURNAL OF VOICE　30　(3)　263-271　2016年5月

DOI： 10.1016/j.jvoice.2015.05.003 　

ISSN：0892-1997

eISSN：1873-4588
NRF2活性化による強大音曝露に伴う酸化ストレスからの内耳保護効果 Nrf2遺伝子欠損マウス解析

本蔵陽平, 水足邦雄, 塩谷彰浩, 川瀬哲明, 香取幸夫, 本橋ほづみ

日本耳鼻咽喉科学会会報　119　(4)　611-611　2016年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
NRF2活性化による強大音曝露に伴う酸化ストレスからの内耳保護効果 50歳聴力への影響

水足邦雄, 本蔵陽平, 川瀬哲明, 香取幸夫, 本橋ほづみ, 塩谷彰浩

日本耳鼻咽喉科学会会報　119　(4)　611-611　2016年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
Cricoarytenoid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial Tissue 国際誌査読有り

Ai Kawamoto-Hirano, Yohei Honkura, Shunichi Shibata, Shin-ichi Abe, Gen Murakami, Yukio Katori

ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY　125　(3)　219-227　2016年3月

DOI： 10.1177/0003489415606450 　

ISSN：0003-4894

eISSN：1943-572X
NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea. 国際誌査読有り

Yohei Honkura, Hirotaka Matsuo, Shohei Murakami, Masayuki Sakiyama, Kunio Mizutari, Akihiro Shiotani, Masayuki Yamamoto, Ichiro Morita, Nariyoshi Shinomiya, Tetsuaki Kawase, Yukio Katori, Hozumi Motohashi

Scientific reports　6　19329-19329　2016年1月18日

DOI： 10.1038/srep19329 　

詳細を見る詳細を閉じる

Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.
音声障害症例に関するHADSを用いた心理的評価の検討

佐藤剛史, 高梨芳崇, 渡邊健一, 本蔵陽平, 平野愛, 太田淳, 川瀬哲明, 香取幸夫

音声言語医学　57　(1)　103-104　2016年1月
出版者・発行元：日本音声言語医学会
ISSN：0030-2813

eISSN：1884-3646
NRF2活性化による、強大音曝露に伴う酸化ストレスからの内耳保護効果の解明

本蔵陽平, 村上昌平, 山本雅之, 川瀬哲明, 香取幸夫, 本橋ほづみ

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[3P1212]-[3P1212]　2015年12月
出版者・発行元： (公社)日本生化学会
顎関節と中耳腔の交通に起因すると考えられた開閉口に伴う他覚性耳鳴の1症例

日高浩史, 本蔵陽平, 山内大輔, 川瀬哲明, 香取幸夫, 小倉正樹, 湯浅有, 小林俊光

耳鼻咽喉科臨床補冊　(補冊142)　99-99　2015年6月
出版者・発行元：耳鼻咽喉科臨床学会
ISSN：0912-1870

eISSN：2185-1557
Bilateral endoscopic endonasal marsupialization of nasopalatine duct cyst. 国際誌査読有り

Yohei Honkura, Kazuhiro Nomura, Hidetoshi Oshima, Yusuke Takata, Hiroshi Hidaka, Yukio Katori

Clinics and practice　5　(1)　748-748　2015年1月28日

DOI： 10.4081/cp.2015.748 　

詳細を見る詳細を閉じる

Nasopalatine duct cysts are the most common non-odontogenic cysts in the maxilla, and are conventionally treated through a sublabial or palatine approach. Recently, the endoscopic approach has been used, but experience is extremely limited. We treated a 29-year-old male with nasopalatine duct cyst by endoscopic marsupialization, but paresthesia of the incisor region occurred after surgery. This paresthesia gradually remitted within 6 months. The nasopalatine nerve, which innervates the upper incisor region, enters two lateral canals separately at the nasal floor and exits the central main canal at the palate. Damage to the bilateral nasopalatine nerves might lead to paresthesia, so we recommend careful examination for nerve fibers during endoscopic surgery, especially if fenestration is performed on both sides.
Pyramidal lobe of the thyroid gland and the thyroglossal duct remnant: A study using human fetal sections 国際誌査読有り

Yoshitaka Takanashi, Yohei Honkura, Jose Francisco Rodriguez-Vazquez, Gen Murakami, Tetsuaki Kawase, Yukio Katori

ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER　197　29-37　2015年

DOI： 10.1016/j.aanat.2014.09.001 　

ISSN：0940-9602

eISSN：1618-0402
Endoscopic Drainage of Orbital Subperiosteal Hematoma Secondary to Acute Rhinosinusitis in a Child 査読有り

Kazuhiro Nomura, Yohei Honkura, Daiki Ozawa, Yuri Okumura, Hiroshi Hidaka, Takenori Ogawa, Daisuke Yamauchi, Kenichi Watanabe, Yukio Katori

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　233　(3)　171-174　2014年7月

DOI： 10.1620/tjem.233.171 　

ISSN：0040-8727

eISSN：1349-3329
Central-part laryngectomy is a useful and less invasive surgical procedure for resolution of intractable aspiration 国際誌査読有り

Ai Kawamoto, Yukio Katori, Yohei Honkura, Risako Kakuta, Kenjiro Higashi, Masaki Ogura, Makiko Miyazaki, Kazuya Arakawa, Kazutaka Kashima, Yukinori Asada, Kazuto Matsuura

EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY　271　(5)　1149-1155　2014年5月

DOI： 10.1007/s00405-013-2725-4 　

ISSN：0937-4477

eISSN：1434-4726
糖尿病合併突発性難聴症例に対するプロスタグランジンE1(PGE1)の治療効果

大越明, 舘田豊, 石井亮, 太田淳, 東賢二郎, 本蔵陽平, 高梨芳崇, 牛来茂樹

日本耳鼻咽喉科学会会報　117　(4)　469-469　2014年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
片側声帯麻痺の手術治療例における静脈麻酔と全身麻酔実施例の検討

河本愛, 本蔵陽平, 野口直哉, 鈴木貴博, 小倉正樹, 中目亜矢子, 沖津尚弘, 佐々木高綱, 香取幸夫

日本耳鼻咽喉科学会会報　117　(4)　477-477　2014年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
Surgical treatment for the aberrant internal carotid artery in the middle ear with pulsatile tinnitus. 国際誌査読有り

Yohei Honkura, Hiroshi Hidaka, Jun Ohta, Shigeki Gorai, Yukio Katori, Toshimitsu Kobayashi

Auris, nasus, larynx　41　(2)　215-8　2014年4月

DOI： 10.1016/j.anl.2013.10.002 　

ISSN：0385-8146

eISSN：1879-1476
Middle ear myoclonus cured by selective tenotomy of the tensor tympani: strategies for targeted intervention for middle ear muscles. 国際誌

Hiroshi Hidaka, Youhei Honkura, Jun Ota, Shigeki Gorai, Tetsuaki Kawase, Toshimitsu Kobayashi

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology　34　(9)　1552-8　2013年12月

DOI： 10.1097/MAO.0000000000000126 　

詳細を見る詳細を閉じる

OBJECTIVE: To describe a case of middle ear myoclonus that was successfully cured by selective transection of the tensor tympani (TT) without sectioning the stapedius tendon (ST) and to review previously reported cases, elucidating precipitating factors for interventions targeting middle ear muscles. DATA SOURCES: One case we encountered and a recent systematic review published in 2012. STUDY SELECTIONS: In addition to our case, 23 cases identified by the previous systematic review regarding middle ear myoclonus in which surgical interventions were conducted. DATA SYNTHESIS: Outcomes for selective tenotomy of TT or ST were analyzed focusing on the following 6 preoperative factors: 1) history of facial palsy, 2) provoking factors for tinnitus, 3) auscultation of the ear, 4) movement of the ear drum, 5) complication with palatal myoclonus, and 6) confirmation of myoclonus during surgery. Among these, the first 2 factors represented significant factors for selective tenotomy of ST (p < 0.05 and p < 0.01, respectively). Furthermore, no auscultation of the ear was significant for selective tenotomy (p < 0.01), specifically for ST. Confirmation of muscle contraction during surgery contributed significantly (p < 0.01) to targeted intervention, but selective tenotomy of TT was successfully performed in 3 cases without such confirmation by confirming variations in compliance with tympanometry CONCLUSION: Assessment of the history of facial palsy, provoking factor of tinnitus, auscultation of the ear, and confirmation of myoclonus during surgery appear helpful in predicting which middle ear muscle is undergoing myoclonus. Furthermore, long-time-based tympanometry offers objective information for planning targeted intervention for middle ear muscles and clarifying clinical outcomes.
Association between Septal Deviation and Sinonasal Papilloma 査読有り

Kazuhiro Nomura, Takenori Ogawa, Mitsuru Sugawara, Yohei Honkura, Hidetoshi Oshima, Kazuya Arakawa, Takeshi Oshima, Yukio Katori

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　231　(4)　315-319　2013年12月

DOI： 10.1620/tjem.231.315 　

ISSN：0040-8727

eISSN：1349-3329
鼓膜張筋腱切断で耳鳴が消失した中耳ミオクローヌスの1症例

日高浩史, 本蔵陽平, 川瀬哲明, 小林俊光

Otology Japan　23　(4)　812-812　2013年10月
出版者・発行元： (一社)日本耳科学会
ISSN：0917-2025

eISSN：1884-1457
Osseous hamartoma arising from the eustachian tube. 国際誌査読有り

Ai Kawamoto, Yukio Katori, Yohei Honkura, Masaki Ogura, Takeshi Oshima, Toshimitsu Kobayashi

Clinics and practice　3　(2)　e25　2013年8月2日

DOI： 10.4081/cp.2013.e25 　

詳細を見る詳細を閉じる

A fairly quite rare case of osseous tumor arising from the Eustachian tube (ET) is described. A 56-year-old man presented with a smooth bulky mass in the nasopharynx and secretory otitis media in the right ear. Computed tomography and magnetic resonance imaging indicated a solid tumor-like region occupying the nasopharynx with apparent extension to the right ET. Transnasal endoscopic surgery demonstrated that the tumor had originated from the ET, and the tumor was partially removed in the area where it had expanded into the nasopharynx. The pathological diagnosis was an osseous hamartoma consisting of bony tissue, fat cells and fibroblasts. To our knowledge, this is the first reported case of osseous hamartoma arising from the ET in the world literature. The patient presented symptoms of nasal obstruction and unilateral aural fullness. Reduction surgery and tympanostomy tube insertion were useful for accurate diagnosis and resolution of the symptoms.
Isolated Juvenile Xanthogranuloma in the Larynx of a Three-Year-Old Child 査読有り

Ai Kawamoto, Yukio Katori, Yohei Honkura, Keiko Ishii, Masaki Ogura, Hiroshi Naganuma, Rie Shibuya, Takahiro Suzuki, Toshimitsu Kobayashi

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　230　(2)　123-127　2013年6月

DOI： 10.1620/tjem.230.123 　

ISSN：0040-8727

eISSN：1349-3329
Acquired Idiopathic Laryngomalacia Treated by Laser Supraglottic Laryngoplasty 査読有り

Ai Kawamoto, Yukio Katori, Yohei Honkura, Masaki Ogura, Yoshitaka Takanashi, Toshimitsu Kobayashi

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE　230　(1)　43-47　2013年5月

DOI： 10.1620/tjem.230.43 　

ISSN：0040-8727

eISSN：1349-3329
鼻骨骨折整復固定後の鼻閉ストレスへのシリコンドレーン留置法の検討

牛来茂樹, 太田淳, 石井亮, 舘田豊, 本蔵陽平, 東賢二郎, 高梨芳崇, 小林俊光

日本耳鼻咽喉科学会会報　116　(4)　489-489　2013年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
披裂部粘膜の軟弱化により吸気時喘鳴を呈した1症例

香取幸夫, 河本愛, 高梨芳崇, 本蔵陽平, 小倉正樹, 鈴木貴博, 小林俊光

日本気管食道科学会会報　64　(2)　s17-s17　2013年4月
出版者・発行元： (NPO)日本気管食道科学会
ISSN：0029-0645

eISSN：1880-6848
幼児の声門下に生じ、減量切除を行った若年性黄色肉芽腫の1症例

河本愛, 石井景子, 本蔵陽平, 小倉正樹, 香取幸夫, 鈴木貴博, 高梨芳崇, 小林俊光

日本気管食道科学会会報　64　(2)　s82-s82　2013年4月
出版者・発行元： (NPO)日本気管食道科学会
ISSN：0029-0645

eISSN：1880-6848
副鼻腔炎根本術後の上顎・篩骨洞に発生したコレステリン肉芽腫の1例

本蔵陽平, 香取幸夫, 河本愛, 小倉正樹, 小林俊光

日本耳鼻咽喉科学会会報　116　(4)　485-485　2013年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
耳管に発生した過誤腫の1症例

河本愛, 香取幸夫, 本蔵陽平, 小倉正樹, 小林俊光

日本耳鼻咽喉科学会会報　116　(4)　529-529　2013年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
重度嚥下障害に対して手術治療を行った44症例の検討

香取幸夫, 河本愛, 本蔵陽平, 小倉正樹, 渡邊健一, 高梨芳崇, 小林俊光

日本耳鼻咽喉科学会会報　116　(4)　553-553　2013年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
Frontal sinusitis with mixed bacterial colonies treated with the combination of endoscopic modified lothrop procedure and external approach. 国際誌査読有り

Kazuhiro Nomura, Yohei Honkura, Yuri Okumura, Atsuko Kasajima, Takahiro Suzuki, Toshiaki Kikuchi, Hiroshi Hidaka, Takeshi Oshima, Yukio Katori

Case reports in otolaryngology　2013　541843-541843　2013年

DOI： 10.1155/2013/541843 　

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Isolated frontal sinusitis with mixed bacterial colonies is extremely rare and has not been described. We report a case of isolated frontal sinus forming mixed bacterial colonies that occurred in the previously exposed frontal sinus. The material in the frontal sinus was macroscopically similar to sinus fungus ball. Surgical strategy followed that for sinus fungus ball. The material could not be completely removed even with an endoscopic modified Lothrop procedure (Draf type III procedure). Additional external incision enabled complete removal of the remnant infectious substance. Histological examination detected two different types of organisms as intermingled bacterial colonies. External approaches to the frontal fungus ball have recently been replaced by the endonasal approach. Our case suggests that material trapped in a pit or small crevice in a frontal sinus may not be removed intranasally.
喉頭蓋嚢胞の穿破が有効であった、妊娠8ヵ月の喉頭蓋炎症例

本蔵陽平, 香取幸夫, 河本愛, 小倉正樹

日本耳鼻咽喉科学会会報　115　(4)　451-451　2012年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN：0030-6622

eISSN：1883-0854
A case of myoepithelioma of the nasal cavity 国際誌査読有り

Kazuhiro Nakaya, Takeshi Oshima, Mika Watanabe, Hiroshi Hidaka, Toshiaki Kikuchi, Kenjiro Higashi, Yohei Honkura, Yosuke Hara, Toshimitsu Kobayashi

AURIS NASUS LARYNX　37　(5)　640-643　2010年10月

DOI： 10.1016/j.anl.2010.03.004 　

ISSN：0385-8146

︎全件表示 ︎最初の5件までを表示

MISC 42

当科における先天性サイトメガロウイルス感染症児の臨床経過の検討

益子怜, 本藏陽平, 高井俊輔, 草野佑典, 須納瀬知輝, 安達美佳, 鈴木淳, 香取幸夫

日本耳科学会総会・学術講演会(Web)　34th　2024年
上半規管裂隙症候群に対する水中内視鏡下plugging後の上半規管の機能について-vHITによる検討

川村善宣, 川村善宣, 川村善宣, 大島英敏, 高井俊輔, 草野佑典, 本蔵陽平, 小林俊光, 川瀬哲明, 香取幸夫

Equilibrium Research　83　(5)　2024年

ISSN： 0385-5716
聴力検査アプリケーションソフトの有用性に関する検討

佐藤剛史, 加藤大雅, 久岡巧麻, 太田淳, 本藏陽平, 香取幸夫, 香取幸夫

耳鼻咽喉科臨床補冊　(166)　2024年

ISSN： 0912-1870
狭小腔手術で微細操作が可能なスティックアームを備えた耳科内視鏡の開発

山内大輔, 本藏陽平, 石井亮, 太田淳, 鈴木淳, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　126　(4)　653-653　2023年4月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN： 2436-5793

eISSN： 2436-5866
転写因子Nrf2を標的とした新たな老人性難聴予防機構の解明

本藏陽平

日本耳科学会総会・学術講演会抄録集　32回　48-48　2022年10月
出版者・発行元： (一社)日本耳科学会
Ndufs4の欠失が音響曝露後の聴覚に及ぼす影響

逸見朋隆, 鈴木淳, 本藏陽平, 池田怜吉, 橋本研, 川瀬哲明, 香取幸夫

日本耳鼻咽喉科頭頸部外科学会会報　125　(4)　730-730　2022年4月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN： 2436-5793

eISSN： 2436-5866
喉頭枠組み手術を行う片側性声帯麻痺患者の発話検査

香取幸夫, 佐藤剛史, 平野愛, 本藏陽平, 渡邊健一

日本気管食道科学会会報　73　(2)　s10-s10　2022年4月
出版者・発行元： (NPO)日本気管食道科学会
ISSN： 0029-0645

eISSN： 1880-6848
耳科手術の最善手を求めて

本藏陽平

日本耳科学会総会・学術講演会抄録集　31回　75-75　2021年10月
出版者・発行元： (一社)日本耳科学会
多様な医師像を目指そう基礎研究と短期留学後に見える、臨床医としての新たな世界

本藏陽平

日本耳鼻咽喉科学会会報　123　(4)　959-959　2020年9月
出版者・発行元： (一社)日本耳鼻咽喉科頭頸部外科学会
ISSN： 0030-6622

eISSN： 1883-0854
声帯麻痺症例の検討

長谷川航世, 渡邊健一, 本藏陽平, 鹿島和孝, 平野愛, 佐藤剛史, 香取幸夫

喉頭　31　(2)　163-167　2019年12月
出版者・発行元：日本喉頭科学会
ISSN： 0915-6127

eISSN： 2185-4696

詳細を見る詳細を閉じる

当院で経験した声帯麻痺168例を検討した。その結果、平均年齢は62.0歳で、男性104例、女性64例であった。患側は左107例、右37例、両側24例であった。原因は腫瘍性が65例と最多で、心臓大血管性44例、特発性21例、挿管性16例の順であった。経過観察中に32例(19.0%)で声帯麻痺の回復がみられ、回復に要した期間は平均3.6ヵ月であった。原因別では挿管性で麻痺の回復率が高かった。片側声帯麻痺の回復を認めなかった61例中37例で音声改善手術が行われたが、術式は披裂軟骨内転術+甲状軟骨形成術1型が36例、甲状軟骨形成術1型が1例であった。音声治療は12例で行われ、それぞれ6例が麻痺回復し、6例が麻痺回復せず、うち2例に音声改善手術が施行されていた。
【進化する経外耳道的内視鏡下耳科手術(TEES)-エキスパートに学ぶスタンダードな手術手技】TEESのスタンダードな手術手技癒着性中耳炎に対する鼓室形成術

山内大輔, 本藏陽平

耳鼻咽喉科・頭頸部外科　91　(11)　934-939　2019年10月
出版者・発行元： (株)医学書院
ISSN： 0914-3491

eISSN： 1882-1316
Ndufs4欠損マウスにおける顎下腺・副腎の形態異常とステロイド合成障害

小林祐太, 本藏陽平, 阿部高明, 大和田祐二, 香取幸夫

耳鼻咽喉科ニューロサイエンス　33　38-41　2019年5月
出版者・発行元：耳鼻咽喉科ニューロサイエンス研究会

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NDUFS4欠損マウスの顎下腺、副腎の組織学的評価を行い、電子伝達系がステロイド合成へ関与していることを示唆する所見を得たので報告した。マウスは(全身性)Ndufs4ノックアウトの雄を用いた。7週齢まで飼育し、顎下腺、精巣、副腎を採取して組織学的評価(Hematoxylin Eosin染色、免疫組織学的手法、Oil-Red O染色)を行った。同時に血液を採取し、血漿アンドロゲン濃度測定を行った。くわえて、マウスTM3細胞株(精巣Leydig細胞株、非腫瘍性)に対して免疫細胞染色、Western Blotを用いたNDUFS4発現評価を行った。Ndufs4ノックアウト雄マウスにおいて、顎下腺で、アンドロゲン依存性に線条部導管に好酸性顆粒を貯留した特殊な導管系(GCT)の著明な発達不良を認めた。この背景として、精巣には明らかな形態異常は認められなかったものの、血漿アンドロゲン濃度は明らかな低値傾向を示した。TM3細胞株において免疫細胞染色、Western BlotによるタンパクレベルでのNDUFS4の発現が確認された。くわえてNdufs4ノックアウト雄マウスにおいて、副腎皮質束状層でも形態学的異常を認めた。Oil-Red O染色の結果、精巣間質および副腎皮質において脂肪滴の減少〜枯渇をきたしていることが示唆された。
早期喉頭癌に対し行われた経口的腫瘍切除術の治療成績

舘田豊, 渡邊健一, 清水佑一, 橋本光, 白倉真之, 太田淳, 平野愛, 本藏陽平, 鈴木淳, 小川武則, 香取幸夫

日本耳鼻咽喉科学会会報　122　(4)　707-707　2019年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
Underwater法による人工内耳埋め込み術の灌流液について査読有り

山内大輔, 本蔵陽平, 清水佑一, 橋本光, 舘田豊, 鈴木淳, 日高浩史, 川瀬哲明, 香取幸夫

日本耳鼻咽喉科学会会報　122　(4)　614-614　2019年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
神経線維腫症II型患者に人工内耳挿入後、MRIにより人工内耳磁石逸脱を来した1例査読有り

日高浩史, 須納瀬知輝, 本蔵陽平, 山内大輔, 香取幸夫

日本耳鼻咽喉科学会会報　122　(4)　615-615　2019年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
ゴアテックスを使用した甲状軟骨形成術1型の術後合併症

渡邊健一, 平野愛, 本藏陽平, 鹿島和孝, 白倉真之, 香取幸夫

日本気管食道科学会会報　70　(2)　s31-s31　2019年4月
出版者・発行元： (NPO)日本気管食道科学会
ISSN： 0029-0645

eISSN： 1880-6848
声門下狭窄症例の気道確保における体外循環ECMOの使用経験

白倉真之, 渡邊健一, 橋本光, 本藏陽平, 石田英一, 野村和弘, 香取幸夫

日本耳鼻咽喉科学会会報　121　(11)　1395-1400　2018年11月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
C57BL/6背景の遺伝子改変マウスを用いた難聴研究のピットホール "Passenger Gene"の問題点について

鈴木淳, 本藏陽平, 川瀬哲明, 香取幸夫

Otology Japan　28　(4)　391-391　2018年9月
出版者・発行元： (一社)日本耳科学会
ISSN： 0917-2025

eISSN： 1884-1457
耳管開放症患者における鼻声の検討査読有り

池田怜吉, 宮崎浩充, 小林俊光, 本蔵陽平, 川瀬哲明, 香取幸夫

Otology Japan　28　(4)　413-413　2018年9月
出版者・発行元： (一社)日本耳科学会
ISSN： 0917-2025

eISSN： 1884-1457
人工内耳埋め込み術が奏功したANCA関連血管炎性中耳炎(OMAAV)の一症例

高井俊輔, 山内大輔, 本藏陽平, 白倉真之, 小林祐太, 日高浩史, 川瀬哲明, 香取幸夫

Otology Japan　28　(4)　396-396　2018年9月
出版者・発行元： (一社)日本耳科学会
ISSN： 0917-2025

eISSN： 1884-1457
人工内耳挿入後、MRIにより人工内耳磁石逸脱をきたした神経線維腫症2型の一例査読有り

須納瀬知輝, 日高浩史, 白倉真之, 本蔵陽平, 山内大輔, 香取幸夫

Otology Japan　28　(4)　398-398　2018年9月
出版者・発行元： (一社)日本耳科学会
ISSN： 0917-2025

eISSN： 1884-1457
老化と聴力障害 : 酸化ストレスによる内耳障害予防に対する転写因子NRF2の機能 (特集老化の分子基盤)

本蔵陽平

医学のあゆみ　266　(8)　588-591　2018年8月25日
出版者・発行元：医歯薬出版
ISSN： 0039-2359
頭頸部領域に発生したspindle cell carcinomaの5例

高橋ひより, 渡邊健一, 白倉真之, 本藏陽平, 山内大輔, 香取幸夫

耳鼻咽喉科臨床　111　(8)　557-563　2018年8月
出版者・発行元：耳鼻咽喉科臨床学会
DOI： 10.5631/jibirin.111.557 　

ISSN： 0032-6313

eISSN： 1884-4545
体外循環下に気道確保を行った声門下狭窄症の1例

白倉真之, 渡邊健一, 本藏陽平, 香取幸夫

耳鼻咽喉科臨床補冊　(補冊153)　94-94　2018年6月
出版者・発行元：耳鼻咽喉科臨床学会
ISSN： 0912-1870

eISSN： 2185-1557
自己フィブリン糊の使用効果を検証する耳鼻咽喉科領域におけるCryoSeal systemによる完全自家血フィブリン糊の使用経験

山内大輔, 本藏陽平, 渡邊健一, 香取幸夫

日本輸血細胞治療学会誌　64　(2)　238-238　2018年4月
出版者・発行元： (一社)日本輸血・細胞治療学会
ISSN： 1881-3011

eISSN： 1883-0625
生体ヒツジを用いた水中内視鏡下耳科手術トレーニング

山内大輔, 本藏陽平, 原陽介, 大石哲也, 鹿島和孝, 荒川一弥, 日高浩史, 香取幸夫

日本耳鼻咽喉科学会会報　121　(4)　570-570　2018年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
鼓室形成術を要した潜在性中耳異物による慢性中耳炎の2症例査読有り

須納瀬知輝, 本蔵陽平, 山内大輔, 日高浩史, 川瀬哲明, 香取幸夫

日本耳鼻咽喉科学会会報　121　(4)　594-594　2018年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
耳管開放症患者における「鼻声」に関する検討査読有り

鈴木陽子, 池田怜吉, 宮崎浩充, 小林俊光, 川瀬哲明, 菊地俊晶, 大島英敏, 佐藤剛史, 本蔵陽平, 香取幸夫

音声言語医学　59　(1)　91-91　2018年1月
出版者・発行元：日本音声言語医学会
ISSN： 0030-2813

eISSN： 1884-3646
水中内視鏡下耳科手術(UWEES)に使用する灌流液についての検討

山内大輔, 原陽介, 本藏陽平, 日高浩史, 川瀬哲明, 香取幸夫

Equilibrium Research　76　(5)　519-519　2017年10月
出版者・発行元： (一社)日本めまい平衡医学会
ISSN： 0385-5716

eISSN： 1882-577X
根治的放射線療法後の頭頸部癌患者におけるEAT-10と嚥下機能評価の関連について

佐藤剛史, 加藤健吾, 石井亮, 本藏陽平, 大石哲也, 白倉真之, 小林祐太, 原陽介, 太田淳, 小川武則, 渡邊健一, 香取幸夫

嚥下医学　6　(2)　247-247　2017年9月
出版者・発行元：日本嚥下医学会
ISSN： 2186-3199
頭頸部癌化学放射線療法中の経口摂取中止および嚥下機能の胃瘻依存への影響

石井亮, 加藤健吾, 佐藤剛史, 大石哲也, 本藏陽平, 白倉真之, 小林祐太, 原陽介, 平野愛, 鹿島和孝, 香取幸夫

嚥下医学　6　(2)　248-249　2017年9月
出版者・発行元：日本嚥下医学会
ISSN： 2186-3199
頭頸部癌根治的化学放射線療法における舌根-咽頭後壁間距離の変化と絶食期間、照射後嚥下障害との関係

加藤健吾, 石井亮, 佐藤剛史, 大石哲也, 本藏陽平, 原陽介, 白倉真之, 小林祐太, 鹿島和孝, 平野愛, 香取幸夫

嚥下医学　6　(2)　249-249　2017年9月
出版者・発行元：日本嚥下医学会
ISSN： 2186-3199
Underwater techniqueによる残存聴力活用型人工内耳埋め込み術について

山内大輔, 本藏陽平, 原陽介, 野村有理, 八幡湖, 高梨芳崇, 安達美佳, 太田淳, 佐藤剛史, 佐々木志保, 和野紗央里, 日高浩史, 川瀬哲明, 香取幸夫

Audiology Japan　60　(5)　292-292　2017年9月
出版者・発行元： (一社)日本聴覚医学会
ISSN： 0303-8106

eISSN： 1883-7301
ミトコンドリアを標的とした新規化合物MA-5の内耳保護効果の検討査読有り

本蔵陽平, 荒川一弥, 池田怜吉, 川瀬哲明, 香取幸夫

耳鼻咽喉科ニューロサイエンス　31　35-36　2017年5月
出版者・発行元：耳鼻咽喉科ニューロサイエンス研究会
長尺状の医療器具の保持機構を備えた水中耳科手術用内視鏡システムの開発

山内大輔, 松永忠雄, 本藏陽平, 原陽介, 荒川一弥, 日高浩史, 川瀬哲明, 芳賀洋一, 香取幸夫

日本耳鼻咽喉科学会会報　120　(4)　587-587　2017年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
誤嚥防止術としての喉頭中央部分切除術の有効性の検証

加藤健吾, 平野愛, 逸見朋隆, 渡邉幸二郎, 小倉正樹, 本藏陽平, 石井亮, 大石哲也, 香取幸夫

日本耳鼻咽喉科学会会報　120　(4)　608-608　2017年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
NRF2依存性環境ストレス応答：内耳酸化ストレス障害の軽減に対するNRF2の貢献国際誌

本蔵陽平, 川瀬哲明, 香取幸夫, 本橋ほづみ, 松尾洋孝, 村上昌平, 崎山真幸, 水足邦雄, 塩谷彰浩, 山本雅之, 森田一郎, 四ノ宮成祥

日本毒性学会学術年会　43　(0)　S13-3　2016年
出版者・発行元：日本毒性学会
DOI： 10.14869/toxpt.43.1.0_S13-3 　

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転写因子NRF2は酸化ストレスによる組織障害からの防御機構を担う重要な制御因子である。最近の報告から、強大音曝露によってもたらされる内耳性聴覚障害は、虚血再還流による酸化ストレスの増加がもたらす組織障害であることが明らかにされた。すなわち、強大音に曝露されている間は内耳の血流量が減少し、曝露後にその回復が起こることにより、活性酸素種が発生し組織障害・細胞機能の低下が生じる。我々は、NRF2の活性化が、心臓や脳、腎臓などの臓器における虚血再灌流障害の軽減に有効であると報告されていることから、強大音曝露による内耳障害の軽減にも有効であると予想し、その検証を行った。その結果、Nrf2^–/–マウスは野生型マウスと比較して強大音曝露により内耳障害が生じ易いことが明らかになった。そこで、NRF2誘導剤であるCDDO-Imを強大音曝露前に投与したところ、内耳障害が軽減された。この改善効果はNrf2^–/–マウスでは認められなかったことから、CDDO-Imによる内耳保護作用はNRF2の活性化によるものであることが確認された。ヒトにおいては、NRF2遺伝子プロモーター領域に一塩基多型があり、NRF2の発現量とその活性の程度に影響することが知られている。そこで、健康診断を受検した602人の陸上自衛隊員の聴力検査の結果とNRF2遺伝子の一塩基多型の相関を検討したところ、騒音性難聴の初期症状を示す集団で、NRF2が少なめになる一塩基多型を有する頻度が有意に高いことがわかった。以上のことより、NRF2の活性化が騒音性難聴の予防に重要であると結論される。また、NRF2遺伝子の発現が低い一塩基多型を有する場合は、騒音性難聴に対するリスクが高くなるので強大音の曝露に対して注意が必要といえる。
ご遺体を用いた頭頸部手術手技研修と研究

香取幸夫, 小川武則, 本蔵陽平, 平野愛

日本気管食道科学会会報　67　(2)　90-92　2016年
出版者・発行元：特定非営利活動法人日本気管食道科学会
DOI： 10.2468/jbes.67.90 　

ISSN： 0029-0645
喉頭蓋基部を牽引し下顎骨に固定する低侵襲な喉頭挙上術の検討

河本愛, 本藏陽平, 高梨芳崇, 渡邊健一, 小倉正樹, 香取幸夫

日本耳鼻咽喉科学会会報　118　(4)　503-503　2015年4月
出版者・発行元： (一社)日本耳鼻咽喉科学会
ISSN： 0030-6622

eISSN： 1883-0854
顎関節と中耳腔の交通に起因すると考えられた開閉口にともなう他覚性耳鳴の1症例

日高浩史, 本蔵陽平, 山内大輔, 川瀬哲明, 香取幸夫, 小林俊光, 小倉正樹, 湯浅有

ＡＵＤＩＯＬＯＧＹＪＡＰＡＮ　57　(5)　615-616　2014年
出版者・発行元：日本聴覚医学会
DOI： 10.4295/audiology.57.615 　

ISSN： 0303-8106
中耳ミオクローヌスの原因筋推定に関与する因子について〜メタ分析より〜

日高浩史, 本蔵陽平, 川瀬哲明, 小林俊光

Audiology Japan　56　(5)　669-670　2013年9月30日
出版者・発行元：日本聴覚医学会
DOI： 10.4295/audiology.56.669 　

ISSN： 0303-8106
診断に苦慮した難治性口腔咽頭潰瘍の4症例

西川仁, 本蔵陽平, 日高浩史

耳鼻咽喉科免疫アレルギー　29　(1)　7-13　2011年12月29日
出版者・発行元：日本耳鼻咽喉科免疫アレルギー学会
DOI： 10.5648/jjiao.29.7 　

ISSN： 0913-0691

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難治性の口腔咽頭潰瘍（びらんおよびアフタ性潰瘍）で，初回精査にて診断がつかず，その後の経過にて新たな診断に至った症例を経験した。4症例のうち2例は類天疱瘡，他の2例はベーチェット病であった。初診時の生検や血清学的検査では確定診断に至らなかった。全身性疾患の中には，口腔咽頭症状が初発にて，確定診断に必要な免疫組織学的検査陽性や他臓器症状の出現までに，期間を要するものがある。難治性の口腔咽頭潰瘍症例に遭遇した時は，再燃時にも他症状の確認と他科への積極的精査依頼が重要であると考えた。<br>

︎全件表示 ︎最初の5件までを表示

共同研究・競争的資金等の研究課題 7

加齢性難聴ならびに音響性聴覚障害の予防から導く、加齢と認知症に対する日米共同対策

香取幸夫, 清水佑一, 本藏陽平, 逸見朋隆, 鈴木淳

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Fund for the Promotion of Joint International Research (International Collaborative Research)

研究機関：Tohoku University

2023年9月8日～ 2028年3月31日
転写因子Nrf2の細胞保護・抗炎症作用に着目した、嚥下障害新規治療法の研究

香取幸夫, 井上誠, 本藏陽平, 池田怜吉, 岡崎達馬, 杉山庸一郎, 白石成, 平野愛, 鈴木淳

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2022年4月1日～ 2025年3月31日

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小動物用嚥下透視装置の記録において前年度にフレームロスの問題が生じていたが、記録用ソフトウエアの臨床現場で用いているものに変更して適切にセッティングを進めたことで、1秒あたり30フレームでコマ落ちのない正確な記録を可能とした。この嚥下造影システムでC57BL6系列のマウスを用い、若年正常マウスにおける嚥下口腔期機能の指標（顎開閉距離、挺舌回数/嚥下回数）および嚥下咽頭期機能の指標（咽頭通過時間、食塊面積）について標準値を求めた。同系列の①亜鉛欠損食を与えたマウス、②酸化ストレスに脆弱性のある転写因子Nrfの遺伝子改変マウス、③アルコール接収（腹腔内投与）を負荷したマウス、ならびに④加齢モデルマウスについて嚥下造影検査を指向した。①、②、③のマウス群では嚥下口腔期機能の低下を示唆する結果が得られた。一方で嚥下咽頭期の機能には正常例と比べて有意な差は現れていない。④については動物の長期飼育・実験中である。鼻腔からリポポリサッカライドを投与する誤嚥モデルマウスを作成し、酸化ストレスに脆弱性のある転写因子Nrfをノックアウトした遺伝子改変マウスと野生型を用いて、体重増減ならびに嚥下関連筋（舌筋、顎二腹筋）、横隔膜、肺組織の評価を行った。Nrfをノックアウトしたマウスは体重の減少が著しく、組織では肺炎がより重度で、嚥下筋群や横隔膜の萎縮の程度が大きく、誤嚥性肺炎の重症度と嚥下関連筋の萎縮が相関することが示唆された。人の嚥下機能の評価に、新たに超音波Bモード画像のスペクトルトラッキングによる嚥下運動解析法を検討し、体表から低侵襲で行える検査として有望であることを示した。人において、酸化ストレスに脆弱性のある一塩基多型が嚥下機能の低下や誤嚥性肺炎の発症頻度や重症洞に関係するかどうかを検討する観察研究を多施設で進めるために研究計画の立案と研究倫理審査申請を進めた。
転写因子Nrf2の細胞保護・抗炎症作用に着目した、嚥下障害新規治療法の研究

香取幸夫, 井上誠, 杉山庸一郎, 鈴木淳, 岡崎達馬, 本藏陽平, 白石成, 平野愛, 池田怜吉

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2022年4月1日～ 2025年3月31日
転写因子Nrf2と細胞死フェロトーシスを標的とした新たな加齢性難聴予防機構の解明

本藏陽平

2021年4月1日～ 2025年3月31日

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本研究は不可逆的とされている加齢性難聴の予防法を確立することを目的としている。高齢化が進む本邦では、加齢性難聴への対策は健康長寿社会の実現に必要かつ急務な課題である。加齢性難聴の主要因は酸化ストレス障害であることが明らかになっているが、未だ臨床的に有効な難聴予防法は確立されていない。フェロトーシスは細胞内の鉄代謝を介した酸化ストレスに依存する機構であり、アポトーシス、ネクローシス、オートファジーとは異なる新たな細胞死メカニズムである。そこで、特に中枢聴覚におけるNrf2とフェロトーシスに着目して解析を進める計画である。具体的には、加齢性難聴における中枢聴覚でのフェロトーシスの機構を明らかにすること、および、Nrf2とフェロトーシスの関連に着目して加齢性難聴の新規予防メカニズムを明らかにすること、の2点を本研究の目標としている。野生型マウスおよびNrf2遺伝子欠損マウスについて、自然老化、およびD-ガラクトース投与による加齢性難聴モデルマウスを用いた検討を計画している。これらのマウスの中枢聴覚のうち蝸牛神経核と上オリーブ核と外側毛帯と下丘について組織学的および細胞生物学的に検討する予定である。本年度は、加齢性難聴モデルマウスの作成過程であり、またD-ガラクトースの投与量や投与間隔および解析に適した週齢について条件検討中であるが、条件が定まり次第、解析を開始することが可能である。そして、組織学的検討および細胞生物学的検討の準備も整いつつある。
流体力学に基づいた水中下直接的蝸牛内ドラッグデリバリーの開発に関する研究

山内大輔, 本藏陽平

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

研究種目：Grant-in-Aid for Scientific Research (C)

研究機関：Tohoku University

2020年4月1日～ 2023年3月31日

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我々はこれまでに、内耳のソフトサージェリーを目的とした水中内視鏡下耳科手術を提案している。水中下のドラッグデリバリーは内耳保護に有効と考えられるが、さらに標的への拡散性・効率性が高い方法の開発が必要である。本研究では、流体力学に基づいた、より安全で効率性の高い直接的な蝸牛内ドラッグデリバリーを検証し、聴覚機能温存や内耳再生医療において広く利用されることを期待して計画した。前年度は（１）のために側頭骨模型を用いた水中下内耳灌流時の内耳圧の検討を行うための側頭骨模型の設計、作製方法について検討した。医療用模型作製についての専門家の意見を参考にし、内耳構造をどこまで再現すれば圧測定が可能かどうか、また３Dプリントの方法について検討した。側頭骨DICOMデータよりVolume Extractor 3.0(i-Plants System Corporation)にてSTLファイルを作成し、これをPOLYGONALmeister(日本ユニシス・セクセリューションズ）にて形成した（https://www.excel.co.jp/polygon/exp/03/）。今年度は３Dプリント用に作成した側頭骨モデルのデータに基づいて、株式会社JMCの３Dプリントチームと相談して再設計し、3種類の側頭骨模型を作製した。一つはDDSを想定しているが、ほかに上半規管裂隙症候群や人工内耳挿入などの実際に水中下で行っている手術の側頭骨内耳模型も作製した。いずれも透明な樹脂でプリントされているため、灌流液が透見され、観察しやすいことがわかった。また着色水を用いるとより鮮明になった。また微細径の圧力センサを作製し、側頭骨モデルを用いた測定実験の準備を整えた。側頭骨モデルの内耳空間に連続する微細径の孔にチューブを固定し、そこから圧力センサを挿入できるようにした。
PGC-1α/Nrf2経路に着目した運動による難聴予防機序の解明と予防法の開発

香取幸夫, 永富良一, 本藏陽平, 池田怜吉, 鈴木淳, 川瀬哲明

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

研究種目：Grant-in-Aid for Scientific Research (B)

研究機関：Tohoku University

2018年4月1日～ 2022年3月31日

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内耳におけるPGC-1α/Nrf2経路の局在を検討するための基礎実験として、PGC-1αの局在およびNrf2経路の効果と作用部位の解析を行った。さらに難聴の予防におけるNrf2経路の効果が酸化ストレスからの防御にあることから、酸化ストレス防御に関与するミトコンドリアに着目し、ミトコンドリア機能異常をもつマウスの検討を研究に含めた。・内耳蝸牛におけるPGC-1αの局在に関しては、進捗状況の項で記すように、まだ再現性のある結果が得られていない。・一方、Nrf2経路の難聴予防に対する効果と作用部位については、先行研究と同様に検証を行い、騒音暴露による負荷をかけたマウス内耳においてNrf2の発現を抑えたマウスで難聴の程度が高く回復が損なわれること、さらにその障害がNrf2活性化薬である2-cyano-3,12 dioxooleana-1,9 dien-28-imidazolide (CDDO-Im)により軽減されることを確認した。過去の報告と同様に、Nrf2活性化薬が騒音負荷によって生じた酸化ストレスから蝸牛を保護していることが示唆された。その作用部位については、難聴を生じたマウスの組織像から有毛細胞および蝸牛外側壁であることが類推された。・ミトコンドリア機能障害が酸化ストレスの原因になることから、ミトコンドリア病モデルマウスの聴力およびその蝸牛の形態変化を検討した。ミトコンドリア病モデルマウスでは対照に比べて加齢とともに早期に難聴を呈すること、および蝸牛のラセン神経節およびラセン靭帯の下方の細胞が減少することを見出した。これらの研究の実施に加え、日本耳鼻咽喉科学会、日本聴覚医学会、アジアオセアニア耳鼻咽喉科頭頸部外科学会に出席し、難聴を研究領域をする国内外の研究者と情報交換を行った。
酸化ストレス内耳障害の病態と予防法解明のためのNrf2の局在および動態の解析

本藏陽平

提供機関：Japan Society for the Promotion of Science

制度名：Grants-in-Aid for Scientific Research

研究種目：Grant-in-Aid for Early-Career Scientists

研究機関：Tohoku University

2018年4月1日～ 2021年3月31日

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Nrf２の活性化による抗酸化作用の向上により難聴を予防できるのではないかとの仮説の下、現在、酸化ストレス内耳障害のモデルとして、加齢性難聴に着目して解析を進めている。加齢性難聴の進行とNrf2との関連を明らかにするため、ある薬剤混餌をC57BL/6マウスに投与し長期的にNrf2の活性化状態を維持する実験系を確立した。このマウスを８ヶ月齢まで長期飼育し解析した。このマウス蝸牛組織を用いたRT-PCRでの解析により、実際にNrf2が活性化されていることを確認した。また、聴性脳幹反応（ABR）での解析により、このNrf2活性マウスは加齢性難聴の進行が抑制されていることも明らかにした。さらに組織学的な検討により、蝸牛のラセン神経節細胞数の加齢にともなう減少がNrf２の活性化により妨げられていることを明らかにした。この結果から、臨床的な加齢性難聴予防法の一つとして、薬剤の長期投与が有用である可能性が示唆される。一方、過去の報告では、加齢性難聴には多様な要因が関連しており、それぞれの要因によって内耳障害の形態的な差異が認められるのではないかと推察されるものの、不明な点が多い。酸化ストレスが主要因である難聴の組織学的な障害の特徴も不明であり、それを明らかにすることを目的に、ミトコンドリア機能異常症モデルの遺伝子改変マウスを用いて解析をおこなった。このマウスはABRでの解析により、早期から難聴が進行することを明らかにした。また、このマウスの蝸牛の組織学的な検討により、ラセン神経節とラセン靭帯で細胞密度が減少しているという特徴を見出した。つまり、酸化ストレスによる内耳障害を予防するためには内耳の特定の細胞の機能維持が特に重要である可能性がある。将来的な難聴予防薬の投与経路の検討のために重要な所見である。

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