鼻副鼻腔粘膜悪性黒色腫におけるTRIM27の検討　　　　　　　　　　　　　　　
木村 将吾, 中丸 裕爾, 鈴木 正宣, 中薗 彬, 本間 あや, 渡邉 良亮, 加納 里志, 対馬 那由多, 鈴木 崇祥, 井戸川 寛志, 本間 明宏, 渡部 昌, 近藤 豪, 畠山 鎮次
日本鼻科学会会誌, 63, 3, 336, 336, (一社)日本鼻科学会, 2024年09月
日本語

Evaluation of Semicircular Canal Function in Relapsing Polychondritis Patients with Dizziness and Sensorineural Hearing Loss Using Video Head Impulse Test.
Kimiko Hoshino, Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hideaki Takeda, Yuji Nakamaru, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 2024年08月26日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To evaluate semicircular canal function using video head impulse test (vHIT) in relapsing polychondritis (RP) patients presenting with dizziness and sensorineural hearing loss. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Three patients with RP underwent vHIT and hearing tests. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined, and the correlation between semicircular canal dysfunction and hearing loss was investigated. RESULTS: Of the six ears, five exhibited semicircular canal dysfunction. Among these, one ear showed dysfunction in two semicircular canals, while the remaining four ears demonstrated dysfunction in all three semicircular canals. Sensorineural hearing loss, ranging from moderate to profound, was detected by pure-tone audiometry in all six ears. Furthermore, a significant correlation was observed between VOR gain in the horizontal semicircular canal (HSC) and hearing level. CONCLUSIONS: This study demonstrated semicircular canal dysfunction in RP patients presenting with dizziness and hearing loss using vHIT. Moreover, a significant correlation was found between HSC dysfunction and the severity of hearing loss. While inner ear involvement is a key clinical symptom included in the diagnostic criteria for RP, there have been few reports evaluating vestibular dysfunction, and this is the first report on the evaluation of several cases using vHIT. Accurate assessment of vestibular function by vHIT may facilitate early diagnosis and intervention in RP, potentially improving patient outcomes.

Evaluation of quality of life for patients with resolved facial nerve palsy.
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Kimiko Hoshino, Makoto Kobayashi, Yuji Nakamaru, Yasushi Furuta, Akihiro Homma
Auris, nasus, larynx, 51, 3, 456, 459, 2024年06月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The quality of life (QOL) for patients with resolved facial nerve palsy has not been evaluated adequately. The objective of this study is to investigate QOL for patients with resolved facial nerve palsy. METHODS: Forty-seven patients with resolved facial nerve palsy were included and the patients' QOL was evaluated using the Facial Clinimetric Evaluation Scale (FaCE Scale). RESULTS: Twenty-two of the 47 patients (46.8%) with resolved facial nerve palsy showed impaired QOL, especially in terms of facial comfort and eye comfort. In 10 cases followed-up after the condition was judged to be resolved, the median scores for the FaCE scale at the time the condition was judged to be resolved and at the last visit were 65.5 and 72, respectively. The mean durations from the onset of the palsy to diagnosis of cure and to the last visit were 2.4 ± 1.6 and 4.3 ± 2.2 months, respectively. There was a significant improvement in QOL after the condition was judged to be resolved. CONCLUSION: There were discrepancies between QOL and facial movement as evaluated by physicians in patients in whom facial nerve palsy was resolved as in patients with non-cured facial nerve palsy. Patients' QOL continued to improve even after physicians judged the condition to be resolved and this result indicated that there were cases where improvement in QOL was delayed in comparison to improvement in facial movement.

Evaluation of Semicircular Canal Function Using Video Head Impulse Test in Patients With Peripheral Vestibular Disorders Without Nystagmus.
Keishi Fujiwara, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Hideaki Takeda, Yuji Nakamaru, Akihiro Homma
Cureus, 16, 6, e62786, 2024年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Objectives This study aims to evaluate semicircular canal function using video head impulse test (vHIT) in patients with peripheral vestibular disorders without nystagmus. Methods Patients who underwent vHIT were enrolled in this study, and the proportion of abnormal findings on vHIT in patients without nystagmus was investigated. In addition, the results of vestibular testing were investigated in cases in which both vHIT and caloric testing were performed in patients without nystagmus. Results Forty-six patients (23.4%) of 197 patients who had no abnormal findings on the nystagmus tests, including the gaze nystagmus test, positional nystagmus test, and positioning nystagmus test, showed dysfunction in at least one semicircular canal on vHIT. The most frequent diagnosis was vestibular schwannoma (14/46, 30.4%), and cases with bilateral vestibular dysfunction were also included (12/46, 26.1%). A disorganized pattern of catch-up saccade was observed more frequently in patients with subjective symptoms of dizziness/vertigo compared to those without subjective symptoms. Although the sensitivity of vHIT was low compared to caloric testing, vHIT could detect isolated vertical canal dysfunction not detected by caloric testing. Conclusions vHIT is considered to be a useful test for patients without nystagmus, as vHIT could detect abnormalities in approximately one-quarter of patients without nystagmus. vHIT is considered to be one of the first tests to be performed following nystagmus testing, including the gaze nystagmus test, the positional nystagmus test, and the positioning nystagmus test. On the other hand, there are some cases in which vHIT shows no abnormality while caloric testing shows canal paresis. It is necessary to perform vHIT, bearing in mind that there are abnormalities that cannot be detected by vHIT alone.

Pre- and post-operative semicircular canal function evaluated by video head impulse test in patients with vestibular schwannoma.
Keishi Fujiwara, Shinya Morita, Hiroaki Motegi, Shigeru Yamaguchi, Yukitomo Ishi, Kimiko Hoshino, Atsushi Fukuda, Makoto Kobayashi, Yuji Nakamaru, Miki Fujimura, Akihiro Homma
Auris, nasus, larynx, 51, 3, 542, 547, 2024年06月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To evaluate pre- and post-operative semicircular canal function in patients with vestibular schwannoma (VS) by the video Head Impulse Test (vHIT). METHODS: Nineteen patients with VS who underwent surgery were enrolled in this study. The gain in vestibulo-ocular reflex (VOR) and the degree of scatter in catch-up saccades were examined pre- and post-operatively for the semicircular canals in VS patients. RESULTS: Ten of 19 cases (52.6 %) with VS were defined as demonstrating both superior vestibular nerve (SVN) and inferior vestibular nerve (IVN) impairment from the results of pre-operative vHIT. Hearing level and subjective vestibular symptoms showed significant correlations with pre-operative semicircular canal function. Compared to pre-operative vHIT results, VOR gains within 1 month after surgery were significantly reduced in all three canals; however, significant differences had disappeared in the anterior and posterior semicircular canals at 6 months after surgery. Cases of unknown origin had a significantly greater reduction in posterior semicircular canal function after surgery compared with those with disease of IVN origin. CONCLUSIONS: As vHIT could evaluate pre-operative vestibular nerve impairment, post-operative VOR gain reduction and the degree of vestibular compensation, semicircular canal function evaluated by vHIT provides a good deal of useful information regarding VS patients undergoing surgery compared to caloric testing, and vHIT should be performed pre- and post-operatively for patients with VS.

Validity of endoscopic ossiculoplasty immediately after its introduction for ossicular chain disruption.
Atsushi Fukuda, Shinya Morita, Kimiko Hoshino, Keishi Fujiwara, Yuji Nakamaru, Akihiro Homma
BMC surgery, 24, 1, 149, 149, 2024年05月14日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Transcanal endoscopic ear surgery (TEES) reportedly requires a long learning curve and may be associated with more complications and longer operative times than microscopic ear surgery (MES). In this study, we aimed to examine the usefulness and validity of TEES for ossicular chain disruption in the early stages of its introduction in our institution. METHODS: TEES was performed on 11 ears (10 with congenital ossicular chain discontinuity and 1 with traumatic ossicular chain dislocation), and MES was performed with a retroauricular incision on 18 ears (6 with congenital ossicular chain discontinuity and 12 with traumatic ossicular chain dislocation) in a tertiary referral center. Postoperative hearing results, operative times, and postoperative hospital length of stay were retrospectively reviewed. The Mann-Whitney U test and Fisher's exact test was performed to compare variables between the TEES and MES groups. Pre- and postoperative air- and bone-conduction thresholds and the air-bone gap of each group were compared using the Wilcoxon signed-rank test. The Mann-Whitney U test and Wilcoxon signed-rank was performed to compare the pre- and postoperative air-bone gaps between the diagnoses. RESULTS: No significant differences in the postoperative air-conduction thresholds, bone-conduction thresholds, air-bone gaps, or incidence of air-bone gap ≤ 20 dB were observed between the TEES and MES groups. The air-conduction thresholds and air-bone gaps of the TEES group significantly improved postoperatively. The air-conduction thresholds and air-bone gaps of the MES group also significantly improved postoperatively. No significant difference was observed in the operative times between the groups (TEES group: median, 80 min; MES group: median, 85.5 min). The TEES group had a significantly shorter postoperative hospital stay (median, 2 days) than the MES group (median, 7.5 days). CONCLUSIONS: TEES was considered appropriate for the treatment of ossicular chain disruption, even immediately after its introduction at our institution. For expert microscopic ear surgeons, ossicular chain disruption may be considered a suitable indication for the introduction of TEES.

Increased adiposity to muscle ratio and severity of sinusitis affect quality of life in asthma—Computed tomographic analysis—
Kaoruko Shimizu, Hirokazu Kimura, Naoya Tanabe, Kazuya Tanimura, Shotaro Chubachi, Hiroaki Iijima, Susumu Sato, Nobuyasu Wakazono, Yuji Nakamaru, Kazufumi Okada, Hironi Makita, Houman Goudarzi, Masaru Suzuki, Masaharu Nishimura, Satoshi Konno
Journal of Allergy and Clinical Immunology: Global, 100277, 100277, Elsevier BV, 2024年05月
研究論文（学術雑誌）

Neutrophil Extracellular Trap Formation and Deoxyribonuclease I Activity in Patients with Otitis Media with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Shinya Morita, Yuji Nakamaru, Atsushi Fukuda, Keishi Fujiwara, Masanobu Suzuki, Kimiko Hoshino, Aya Honma, Akira Nakazono, Akihiro Homma
International archives of allergy and immunology, 185, 8, 810, 819, 2024年, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: No previous studies have evaluated the levels of neutrophil extracellular trap (NET) remnants or the importance of deoxyribonuclease (DNase) I activity based on the disease activity of otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). The aim of this study was to explore the formation of NETs in the middle ear of patients with OMAAV during the onset and remission phases of the disease, with a particular focus on the relationships between the quantifiable levels of NET remnants and DNase I activity. METHODS: OMAAV patients were eligible for inclusion. Patients with otitis media with effusion (OME) were examined as controls. The levels of cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex were quantified using an enzyme-linked immunosorbent assay. DNase I activity was measured using a fluorometric method. RESULTS: The quantifiable levels of cell-free DNA, cit-H3-DNA complex, and MPO-DNA complex in the middle ear lavage of patients with OMAAV at onset were significantly higher than those in patients with OMAAV at remission and in patients with OME. DNase I activity in the patients with OMAAV at onset was significantly lower than those in patients with OMAAV at remission and OME and was negatively correlated with the level of MPO-DNA complex. CONCLUSIONS: This study suggests that NET remnants and DNase I activity may be potentially useful biomarkers for the diagnosis and disease activity of OMAAV.

Clinical outcomes for olfactory neuroblastoma.
Akira Nakazono, Hiroaki Motegi, Masanobu Suzuki, Yuji Nakamaru, Shigeru Yamaguchi, Yukitomo Ishi, Satoshi Kano, Nayuta Tsushima, Aya Honma, Takayoshi Suzuki, Shogo Kimura, Seijiro Hamada, Jun Taguchi, Yasushi Shimizu, Takashi Mori, Koichi Yasuda, Hidefumi Aoyama, Ichiro Kinoshita, Miki Fujimura, Akihiro Homma
Frontiers in oncology, 14, 1329572, 1329572, 2024年, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Olfactory neuroblastoma (ONB) is a rare malignant tumor arising from the olfactory neuroepithelium. The standard of care for ONB is surgical resection; however, detailed treatment protocols vary by institution. Our treatment protocol consists of endoscopic skull base surgery (ESBS) for endoscopically resectable cases and induction chemotherapy followed by craniotomy combined with ESBS for locally advanced cases, with postoperative radiotherapy performed for all cases. Chemoradiotherapy (CRT) is performed in unresectable cases. In this study, we evaluate our treatment protocol and outcomes for ONB. METHODS: A retrospective review of patients with ONB was conducted. Outcomes included survival outcomes and perioperative data. RESULTS: Fifteen patients (53.6%) underwent ESBS, 12 (42.9%) underwent craniotomy combined with ESBS, and 1 (3.6%) received CRT. The 5- and 10-year overall survival rates for all patients were 92.9% and 82.5%, respectively, with a median follow-up period of 81 months. The 5- and 10-year disease-free survival rates were 77.3% and 70.3%, respectively, and the 5- and 10-year local control rates were 88.2% and 80.2%, respectively. Patients undergoing ESBS demonstrated a significantly shorter operating time, period from operation to ambulation, hospitalization period, and less blood loss than those undergoing craniotomy combined with ESBS. CONCLUSION: Our treatment protocol was found to afford favorable outcomes. Patients who underwent endoscopic resection showed lower complication rates and better perioperative data than those who underwent craniotomy combined with ESBS. With appropriate case selection, ESBS is considered a useful approach for ONB.

鼓室型グロムス腫瘍の3例　　　　　　　　　　　　　　　
小林 諒, 森田 真也, 福田 篤, 干野 季美子, 藤原 圭志, 中丸 裕爾, 本間 明宏
日本耳科学会総会・学術講演会抄録集, 33回, 296, 296, (一社)日本耳科学会, 2023年11月
日本語

当科における耳小骨離断に対する経外耳道的内視鏡下耳科手術の成績　　　　　　　　　　　　　　　
福田 篤, 森田 真也, 干野 季美子, 小林 諒, 藤原 圭志, 中丸 裕爾, 本間 明宏
日本耳科学会総会・学術講演会抄録集, 33回, 390, 390, (一社)日本耳科学会, 2023年11月
日本語

Targeted next-generation sequencing of Japanese patients with sinonasal mucosal melanomas identifies frequent NRAS and CTNNB1 mutations
Nayuta Tsushima, Satoshi Kano, Kanako C. Hatanaka, Takayoshi Suzuki, Seijiro Hamada, Hiroshi Idogawa, Yuji Nakamaru, Masanobu Suzuki, Yutaka Hatanaka, Akihiro Homma
Auris Nasus Larynx, Elsevier BV, 2023年11月
研究論文（学術雑誌）

Quantitative Evaluations of Vestibular Function in Patients With Petrous Apex Cholesterol Granulomas Treated With an Endoscopic Transsphenoidal Approach: A Report of Two Cases.
Yuuki Fujiwara, Keishi Fujiwara, Hiroaki Motegi, Yukitomo Ishi, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 44, 8, 809, 812, 2023年09月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: We report two cases of petrous apex cholesterol granuloma (PACG) treated with an endoscopic transsphenoidal approach. Vestibular functions of the two patients were evaluated quantitatively by video Head Impulse Test (vHIT) and/or vestibular evoked myogenic potentials (VEMPs). PATIENTS: Two patients with PACG who experienced episodes of dizziness are presented. INTERVENTION: An endoscopic transsphenoidal approach to PACG. MAIN OUTCOME MEASURE: The preoperative and postoperative vestibular functions as evaluated by vHIT and VEMP. RESULTS: Two cases of PACG were treated by a transsphenoidal approach. The internal auditory canal was compressed by the PACG in both cases. The patients both experienced episodes of dizziness before surgery and preoperative vestibular testing including vHIT and VEMP indicated dysfunction of vestibular nerves. After surgery, their symptoms were completely resolved, and the vestibular testing results were improved. CONCLUSIONS: This article is noteworthy for being the first to publish quantitative vestibular function testing for patients with PACG with vestibular dysfunction. PACG may show various symptoms, with dizziness being one of the most common symptoms. In cases in which the internal auditory canal is compressed by the PACG, vestibular functions should be evaluated by vHIT and VEMP. In the present cases, dizziness was found to be resolved by surgery to release the compression on internal auditory canal. Based on the present cases, the transsphenoidal approach is considered to be both safe and effective.

Treatment outcomes of the patient with sinonasal mucosal melanoma: the role of endoscopic resection and postoperative radiotherapy.
Nayuta Tsushima, Satoshi Kano, Koichi Yasuda, Takayoshi Suzuki, Seijiro Hamada, Yuji Nakamaru, Masanobu Suzuki, Yusuke Uchinami, Hidefumi Aoyama, Akihiro Homma
International journal of clinical oncology, 28, 9, 1218, 1226, 2023年06月17日, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The standard of care for sinonasal mucosal melanoma is surgery and postoperative radiotherapy (PORT). Our treatment strategy comprises endoscopic resection and PORT. We performed combined endoscopic and open resection or applied an external approach alone when sufficient resection was difficult to achieve endoscopically. The objective of this study was to evaluate the validity of our treatment strategy. METHODS: We assessed 30 patients with sinonasal mucosal melanoma who underwent definitive therapy between January 2002 and April 2021, and conducted a retrospective analysis. The median follow-up period was 2.2 years. The primary endpoint was overall survival. The Kaplan-Meier method was used for the calculation of survival rates, the cumulative incidence of distant metastasis, and local recurrence. RESULTS: Twenty-eight patients underwent surgery. The other two patients were treated by definitive proton beam therapy. Twenty-one of 28 (75%) patients underwent resection by endoscopic approach alone. Postoperative radiotherapy was performed for all 28 patients who underwent surgery. Twenty-one patients (70%) experienced recurrence during the observation period. Overall, distant metastasis was observed in 19 patients. Twelve patients died during the observation period, with 10 of the 12 patients (83%) dying of distant metastasis. The overall survival rate at 2 and 5 years was 70% and 46%, respectively. The cumulative incidence rate of distant metastasis at 2 years was 63%, while the 2-year cumulative incidence rate of local recurrence was 6.7%. CONCLUSION: The local disease was controlled by our treatment strategy. To improve treatment outcomes, control of the distant metastasis is needed.

疼痛を伴わなかった悪性外耳道炎例
佐藤 禄, 福田 篤, 森田 真也, 藤原 圭志, 中丸 裕爾, 本間 明宏
耳鼻咽喉科臨床, 116, 6, 567, 572, 耳鼻咽喉科臨床学会, 2023年06月
日本語, 症例は76歳男性で、左耳漏、左顔面神経麻痺、嚥下困難の精査加療目的に当科入院となった。入院時、耳痛は認めなかったが、側頭骨CTで左外耳道前壁から鼓室前壁にかけて強い骨融解像を伴う軟部陰影が充満し、頭蓋底の一部にも骨融解像がみられた。第2病日に生検および左後壁保存型鼓室形成術IIIc型を施行し、病理組織所見・画像所見より悪性外耳道炎に合併した頭蓋底骨髄炎の診断に至った。術後は6週間にわたり抗菌薬の静注を続け、頭蓋底病変は改善傾向にあったため、内服に切り替え第52病日に軽快退院した。抗菌薬は内服開始2年後に終了し、顔面神経麻痺は回復し、抗菌薬中止後1年4ヵ月間にわたり明らかな再燃は認めなかった。

TRIM27 expression is associated with poor prognosis in sinonasal mucosal melanoma.
S Kimura, M Suzuki, Y Nakamaru, S Kano, M Watanabe, A Honma, A Nakazono, N Tsushima, S Hatakeyama, A Homma
Rhinology, 2023年03月09日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Tripartite motif-containing 27 (TRIM27) has been implicated in the progression of various cancers. However, the role of TRIM27 in sinonasal mucosal melanoma (SNMM) remains poorly understood. MATERIALS & METHODS: We retrospectively examined 28 patients with SNMM treated with between 2003 and 2021. We undertook immunohistochemical analysis of TRIM27, Ki-67, and p-Akt1 expression in SNMM tissues. We also investigated the relationship between TRIM27 expression and clinical characteristics, prognosis, Ki-67 as a tumor growth potential marker, and p-Akt1 as one of the prognostic factors in mucosal melanoma. RESULTS: TRIM27 expression was significantly higher in T4 disease than in T3 disease and was higher in stage IV than in stage III. Patients with high-TRIM27 SNMM had a significantly poorer prognosis in terms of overall survival (OS) and disease-free survival.There was also a significantly higher rate of distant metastasis. Univariate analysis for OS revealed that TRIM27 and T classification were significant poor prognostic factors. In addition, the Ki-67 positive score and the p-Akt1 total staining score were significantly higher in the high-TRIM27 group than in the low-TRIM27 group. CONCLUSIONS: High TRIM27 expression in SNMM was associated with advanced T classification, poor prognosis and distant metastasis. We suggest that TRIM27 has potential as a novel biomarker for prognosis in SNMM.

Nasal irrigation improving nasal obstruction and QoL of patients: two cases of HHT after nasal dermoplasty
Hideaki Takeda, Masanobu Suzuki, Yuji Nakamaru, Shogo Kimura, Akira Nakazono, Aya Honma, Akihiro Homma
JOURNAL OF JAPAN SOCIETY FOR HEAD AND NECK SURGERY, 32, 3, 299, 303, Japan Society for Head and Neck Surgery, 2023年
研究論文（学術雑誌）

Mental workload during endoscopic sinus surgery is associated with surgeons' skill levels.
Masanobu Suzuki, Kou Miyaji, Kotaro Matoba, Takashige Abe, Yuji Nakamaru, Ryosuke Watanabe, Takayoshi Suzuki, Akira Nakazono, Atsushi Konno, Dominik Hinder, A J Psaltis, P J Wormald, Akihiro Homma
Frontiers in medicine, 10, 1090743, 1090743, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Surgeons' mental workload during endoscopic sinus surgery (ESS) has not been fully evaluated. The assessment was challenging due to the great diversity of each patient's anatomy and the consequence variety of surgical difficulties. In this study, we examined the mental workload of surgeons with various surgical skill levels during ESS under the standardized condition provided by novel-designed 3D sinus models. MATERIALS AND METHODS: Forty-seven participants performed a high-fidelity ESS simulation with 3D-printed sinus models. Surgeons' mental workload was assessed with the national aeronautics and space administration-task load index (NASA-TLX). Associations between the total and subscales score of NASA-TLX and surgical skill index, including the board certification status, the number of experienced ESS cases, and the objective structured assessment of technical skills (OSATS), were analyzed. In addition, 10 registrars repeated the simulation surgery, and their NASA-TLX score was compared before and after the repetitive training. RESULTS: The total NASA-TLX score was significantly associated with OSATS score (p = 0.0001). Primary component analysis classified the surgeons' mental burden into three different categories: (1) the skill-level-dependent factors (temporal demand, effort, and performance), (2) the skill-level-independent factors (mental and physical demand), and (3) frustration. After the repetitive training, the skill-level-dependent factors were alleviated (temporal demand; z = -2.3664, p = 0.0091, effort; z = -2.1704, p = 0.0346, and performance; z = -2.5992, p = 0.0017), the independent factors were increased (mental demand; z = -2.5992, p = 0.0023 and physical demand; z = -2.2509, p = 0.0213), and frustration did not change (p = 0.3625). CONCLUSION: Some of the mental workload during ESS is associated with surgical skill level and alleviated with repetitive training. However, other aspects remain a burden or could worsen even when surgeons have gained surgical experience. Routine assessment of registrars' mental burdens would be necessary during surgical training to sustain their mental health.

アブミ骨手術の術後成績の検討 とくにピストントリミングの有無との関連について
小林 諒, 福田 篤, 森田 真也, 藤原 圭志, 中丸 裕爾, 本間 明宏
耳鼻咽喉科臨床, 115, 9, 747, 752, 耳鼻咽喉科臨床学会, 2022年09月
日本語, 対象は2014年1月～2021年3月の39例44耳(男性10例、女性29例、平均年齢41.8歳)。診断は耳硬化症が30耳、耳小骨奇形が14耳であり、全例で顕微鏡下にstapedotomyを施行しCO2レーザーを用いてアブミ骨底板を開窓した。平均気導聴力は術前58.3dBから術後36.2dBと有意な改善を認めたが、平均骨導聴力は術後有意な変化を認めなかった。平均気骨導差は術前30.5dBから術後8.4dBと有意な改善を認めた。日本耳科学会基準に基づく術後成功例は36耳(81.8%)であった。術後聴力成績に影響を及ぼす因子として、テフロンピストンのリングをトリミングした場合に成功率が有意に低かった。ピストンリングのトリミングを行い成功に至らなかった症例のなかにはキヌタ骨長脚からピストンが脱落している症例もあり、テフロンピストンリングはできる限りトリミングせずに使用することが望ましい。

オマリズマブの長期投与後、投与間隔延長による不応を呈した重症喘息の1例
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 木村 孔一, 中丸 裕爾, 今野 哲
アレルギー, 71, 8, 944, 948, (一社)日本アレルギー学会, 2022年09月
日本語, 現在,重症喘息に対する生物学的製剤の長期使用の報告がなされている.しかし,効果が認められる症例における必要治療継続期間,中止基準については明確な基準はない.今回,オマリズマブによる長期的なコントロール維持の後,投与間隔の延長に伴い,喘息病態が悪化を来たし,その後通常間隔投与に戻したものの,当初の効果を認めなかった重症喘息の1例を経験した.投与間隔を延長したことが,効果減弱に関与した可能性もあり,今後のオマリズマブの長期使用に関する診療の一助となると考え,報告する.(著者抄録)

Association of gene mutations with clinicopathologic features in patients with external auditory canal squamous cell carcinoma.
Shinya Morita, Satoshi Kano, Kanako C Hatanaka, Yutaka Hatanaka, Takayoshi Suzuki, Atsushi Fukuda, Kimiko Hoshino, Keishi Fujiwara, Yuji Nakamaru, Akihiro Homma
International journal of clinical oncology, 27, 9, 1394, 1403, 2022年09月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: External auditory canal squamous cell carcinoma (EACSCC) is a rare form of malignant tumor. Due to the extremely limited understanding of the genomic landscape in EACSCC, the association between gene mutations and clinicopathologic features remains unclear. This study aimed to explore somatic gene mutations associated with the clinicopathological features in patients with EACSCC, and to identify the candidate gene mutations for predicting survival outcome in EACSCC. METHODS: Twenty-two tissue samples obtained from patients with EACSCC were analyzed for genetic mutations based on targeted next-generation sequencing and genetic expression based on IHC staining to investigate the driver of tumorigenesis and/or the candidates of genes for predicting clinical outcome in EACSCC. RESULTS: Gene alterations were most frequently observed in TP53 (59.1%), followed by CREBBP (9.1%). TP53 mutations showed significant correlation with T classification (P = 0.027) and p53 expression phenotype (P < 0.001). The 5-year overall survival (OS) rates for EACSCC patients with TP53 mutations and wild-type TP53 were 45.0% and 75.0%, respectively. Multivariable analysis using the Cox proportional hazards model demonstrated that TP53 mutations were independent predictors of OS rates for EACSCC patients (P = 0.007). CONCLUSION: This study has suggested that TP53 mutations have potential for use as a biomarker for identifying individuals at high risk of developing tumors and for predicting survival outcome in EACSCC. IHC staining for p53 might play a useful role as screening tool for detecting TP53 mutations in patients with EACSCC.

Repetitive simulation training with novel 3D-printed sinus models for functional endoscopic sinus surgeries.
Masanobu Suzuki, Kou Miyaji, Ryosuke Watanabe, Takayoshi Suzuki, Kotaro Matoba, Akira Nakazono, Yuji Nakamaru, Atsushi Konno, Alkis James Psaltis, Takashige Abe, Akihiro Homma, Peter-John Wormald
Laryngoscope investigative otolaryngology, 7, 4, 943, 954, 2022年08月, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The purpose of this study was to find a utility of a newly developed 3D-printed sinus model and to evaluate the educational benefit of simulation training with the models for functional endoscopic sinus surgery (FESS). Material and methods: Forty-seven otolaryngologists were categorized as experts (board-certified physicians with ≥200 experiences of FESS, n = 9), intermediates (board-certified physicians with <200 experiences of FESS, n = 19), and novices (registrars, n = 19). They performed FESS simulation training on 3D-printed models manufactured from DICOM images of computed tomography (CT) scan of real patients. Their surgical performance was assessed with the objective structured assessment of technical skills (OSATS) score and dissection quality evaluated radiologically with a postdissection CT scan. First we evaluated the face, content, and constructive values. Second we evaluated the educational benefit of the training. Ten novices underwent training (training group) and their outcomes were compared to the remaining novices without training (control group). The training group performed cadaveric FESS surgeries before and after the repetitive training. Results: The feedback from experts revealed high face and content value of the 3D-printed models. Experts, intermediates, and novices demonstrated statistical differences in their OSATS scores (74.7 ± 3.6, 58.3 ± 10.1, and 43.1 ± 11.1, respectively, p < .001), and dissection quality (81.1 ± 13.1, 93.7 ± 15.1, and 126.4 ± 25.2, respectively, p < .001). The training group improved their OSATS score (41.1 ± 8.0 to 61.1 ± 6.9, p < .001) and dissection quality (122.1 ± 22.2 to 90.9 ± 10.3, p = .013), while the control group not. After training, 80% of novices with no prior FESS experiences completed surgeries on cadaver sinuses. Conclusion: Repeated training using the models revealed an initial learning curve in novices, which was confirmed in cadaveric mock FESS surgeries. Level of evidence: N/A.

Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Labyrinthine Fistula Due to Cholesteatoma.
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 43, 5, 587, 593, 2022年06月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To evaluate semicircular canal function in patients with labyrinthine fistula (LF) due to cholesteatoma by the video Head Impulse Test (vHIT). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Ten patients with LF due to cholesteatoma and six without LF underwent vestibular examination. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for the semicircular canals in patients with LF. RESULTS: Seven of 10 cases (70.0%) in the fistula group were judged to have semicircular canal dysfunction based on preoperative evaluation. VOR gains in the patients with LF were significantly lower than those in the patients without LF. VOR gain decreased significantly in accordance with the severity of the LF. The postoperative VOR gain more than 6 months after surgery was significantly improved compared with the preoperative VOR gain. CONCLUSIONS: The vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with LF due to cholesteatoma as it is not influenced by middle ear pathology and can evaluate the function of the vertical canals. The vHIT could predict whether a LF is present or not before surgery, and the vHIT is essential for surgery for patients with LF.

Discrepancies in the caloric testing and video Head Impulse Test results in a case with bilateral lateral semicircular canal malformations.
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
Auris, nasus, larynx, 2022年04月22日, ［国際誌］
英語, Lateral semicircular canal (LSCC) malformations represent one of the most common types of inner ear malformation. As many cases of LSCC malformations are asymptomatic, detailed vestibular functions in such cases remain unclear. We present a case with bilateral LSCC malformations for whom the function of each vestibular organ was evaluated by caloric testing, video Head Impulse Test (vHIT) and vestibular evoked myogenic potentials (VEMP). Caloric testing showed canal paresis of the left side, whereas vHIT showed bilateral normal semicircular canal function. The results of VEMP indicated left saccular dysfunction. Discrepancies in caloric testing and vHIT results were observed and these discrepancies are thought to be due to endolymphatic hydrops rather than vestibular hypofunction, similar to that in Meniere disease.

内視鏡下頭蓋底手術を考慮した嗅神経芽細胞腫に対する新規病期分類の検討
中薗 彬, 中丸 裕爾, 鈴木 正宣, 本間 あや, 木村 将吾, 本間 明宏
日本耳鼻咽喉科頭頸部外科学会会報, 125, 4, 702, 702, (一社)日本耳鼻咽喉科頭頸部外科学会, 2022年04月
日本語

難治性喘息 重症喘息における生物学的製剤の変更に影響する因子の検討
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 松本 宗大, 木村 孔一, 中丸 裕爾, 伊藤 陽一, 今野 哲
日本呼吸器学会誌, 11, 増刊, 143, 143, (一社)日本呼吸器学会, 2022年04月
日本語

難治性喘息 重症喘息における生物学的製剤の変更に影響する因子の検討　　　　　　　　　　　　　　　
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 松本 宗大, 木村 孔一, 中丸 裕爾, 伊藤 陽一, 今野 哲
日本呼吸器学会誌, 11, 増刊, 143, 143, (一社)日本呼吸器学会, 2022年04月
日本語

postコロナ・withコロナの耳鼻咽喉科診療 頭頸部の診療　　　　　　　　　　　　　　　
本間 明宏, 中丸 裕爾, 鈴木 正宣, 本間 あや
日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 2回, 71, 71, 日本耳鼻咽喉科免疫アレルギー感染症学会, 2022年03月
日本語

術前呼吸機能検査による鼻茸を伴う副鼻腔炎の予後推測　　　　　　　　　　　　　　　
中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 木村 将吾, 本間 明宏
日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 2回, 77, 77, 日本耳鼻咽喉科免疫アレルギー感染症学会, 2022年03月
日本語

鼻粘膜上皮細胞での細菌・ウィルス結合受容体発現に対する自然免疫シグナルの影響　　　　　　　　　　　　　　　
中薗 彬, 木村 将吾, 本間 あや, 鈴木 正宣, 中丸 裕爾, 本間 明宏
日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 2回, 168, 168, 日本耳鼻咽喉科免疫アレルギー感染症学会, 2022年03月
日本語

鼻粘膜上皮におけるMetallothionein-3発現解析　　　　　　　　　　　　　　　
鈴木 正宣, 中丸 裕爾, 中薗 彬, 本間 あや, 木村 将吾, 本間 明宏
日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 2回, 185, 185, 日本耳鼻咽喉科免疫アレルギー感染症学会, 2022年03月
日本語

The Quantification of Extracellular Trap Cell Death-Derived Products as Diagnostic Biomarkers for Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Eosinophilic Otitis Media.
Shinya Morita, Yuji Nakamaru, Atsushi Fukuda, Keishi Fujiwara, Masanobu Suzuki, Kimiko Hoshino, Aya Honma, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 43, 3, e337-e343, 2022年03月01日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: This study aimed to quantify the cell-free deoxyribonucleic acid (DNA), citrullinated-histone H3 (cit-H3)-DNA complex, and myeloperoxidase (MPO)-DNA complex as extracellular trap cell death (ETosis)-derived products in the middle ear fluid, and to identify diagnostic biomarkers for the discrimination of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) from eosinophilic otitis media (EOM). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: OMAAV patients were eligible for inclusion in this analysis. Patients with EOM were examined as controls. INTERVENTION: All samples were obtained from the middle ear fluid in patients with OMAAV or EOM. The fluid samples were aspirated from the middle ear through the anterior-inferior portion of the tympanic membrane using a 1-ml tuberculin syringe with a 24- or 26-gauge needle under a microscope. MAIN OUTCOME MEASURES: The levels of cell-free DNA, cit-H3-DNA complex and MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay. RESULTS: Patients with OMAAV showed significantly higher levels of MPO-DNA complex compared to patients with EOM, regardless of the serum ANCA status at the time of sampling (p < 0.001 and p < 0.001, respectively). Meanwhile, there were no significant differences in the values of cell-free DNA or cit-H3-DNA complex between the OMAAV and EOM patients. CONCLUSION: The findings of this study suggest that the detection and quantification of MPO-DNA complex in the otitis media fluid can be utilized to discriminate OMAAV, especially in cases of eosinophilic granulomatosis with polyangiitis, from EOM regardless of the serum ANCA status. It should be noted that it is possible for cell-free DNA and cit-H3-DNA complex in fluid samples to be derived from dead cells other than neutrophils that undergo ETosis.

前頭開頭術後に生じた前頭蓋底粘液嚢胞の2例
山田 真司, 鈴木 正宣, 中丸 裕爾, 本間 あや, 中薗 彬, 木村 将吾, 安川 真一郎, 蠣崎 文彦, 本間 明宏
耳鼻咽喉科・頭頸部外科, 94, 2, 183, 187, 2022年02月

[A CASE OF SEVERE ASTHMA RESULTING IN DISEASE EXACERBATION AFTER PROLONGATION OF THE DOSING INTERVAL AFTER LONG-TERM OMALIZUMAB ADMINISTRATION].
Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Hirokazu Kimura, Yuji Nakamaru, Satoshi Konno
Arerugi = [Allergy], 71, 8, 944, 948, 2022年, ［国内誌］
日本語, 研究論文（学術雑誌）, At the time of writing of this manuscript, four biologics were clinically available for the treatment of severe asthma, and there were no established recommendations for the period of administration or timing of discontinuation of each biologic. We present a case of severe asthma that was well controlled with long-term omalizumab treatment; however, prolongation of the dosing intervals resulted in disease exacerbation that was refractory to omalizumab treatment despite the restoration of the recommended interval of administration. We suspect that the prolonged dosing intervals might have reduced the efficacy of omalizumab. We report this case because dosing intervals should be considered in clinical practice in cases of long-term omalizumab treatment.

Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma.
Machiko Matsumoto-Sasaki, Kaoruko Simizu, Masanobu Suzuki, Masaru Suzuki, Hirokazu Kimura, Yuji Nakamaru, Yoichi M Ito, Akihiro Honma, Satoshi Konno
Journal of asthma and allergy, 15, 187, 195, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Biologics have been used increasingly for the treatment of severe asthma. However, established guidelines for the selection, switching, or discontinuation of biologics do not exist. We aimed to identify the clinical characteristics of patients with asthma who required switching biologics and the factors associated with switching biologics. Patients and Methods: This was a retrospective study of 42 patients with severe asthma treated with biologics at the Hokkaido University Hospital between 23rd June 2016 and 30th April 2021, when two biologics were available in Japan. We compared the characteristics of subjects who continued and switched biologics. The time to switch the biologics was assessed by type 2 inflammatory biomarkers, pulmonary function indices, and the presence of comorbidities, including the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score and aspirin exacerbated respiratory diseases (AERD), using the Kaplan-Meier method and a multivariate Cox proportional hazards model. Results: Eight and five patients were treated by mepolizumab and benralizumab at baseline, respectively among the 31% (13/42) who switched the biologics. Subjects who required switching biologics were characterized by high blood eosinophil counts, younger age, JESREC scores of 11 points or higher, and AERD. The time taken to switch biologics was significantly shorter in the subgroups with high JESREC scores (≥11) or AERD, compared with their counterparts with low JESREC scores or without AERD (both, P < 0.05). JESREC scores of ≥11, but not the presence of AERD, were associated with time to switch biologics. Conclusion: The presence of eosinophilic chronic rhinosinusitis based on JESREC scores of ≥11 and younger age were factors associated with switching biologics in asthma.

後天性中耳真珠腫におけるNotchシグナル関連分子発現についての検討　　　　　　　　　　　　　　　
福田 篤, 森田 真也, 藤原 圭志, 干野 季美子, 中丸 裕爾, 本間 明宏
日本耳科学会総会・学術講演会抄録集, 31回, 422, 422, (一社)日本耳科学会, 2021年10月
日本語

Remote Training of Functional Endoscopic Sinus Surgery With Advanced Manufactured 3D Sinus Models and a Telemedicine System
Masanobu Suzuki, Erich Vyskocil, Kazuhiro Ogi, Kotaro Matoba, Yuji Nakamaru, Akihiro Homma, Peter J. Wormald, Alkis J. Psaltis
Frontiers in Surgery, 8, Frontiers Media SA, 2021年10月01日
研究論文（学術雑誌）, Objective: Traditionally, cadaveric courses have been an important tool in surgical education for Functional Endoscopic Sinus Surgery (FESS). The recent COVID-19 pandemic, however, has had a significant global impact on such courses due to its travel restrictions, social distancing regulations, and infection risk. Here, we report the world-first remote (Functional Endoscopic Sinus Surgery) FESS training course between Japan and Australia, utilizing novel 3D-printed sinus models. We examined the feasibility and educational effect of the course conducted entirely remotely with encrypted telemedicine software.

Methods: Three otolaryngologists in Hokkaido, Japan, were trained to perform frontal sinus dissections on novel 3D sinus models of increasing difficulty, by two rhinologists located in Adelaide, South Australia. The advanced manufactured sinus models were 3D printed from the Computed tomography (CT) scans of patients with chronic rhinosinusitis. Using Zoom and the Quintree telemedicine platform, the surgeons in Adelaide first lectured the Japanese surgeons on the Building Block Concept for a three Dimensional understanding of the frontal recess. They in real time directly supervised the surgeons as they planned and then performed the frontal sinus dissections. The Japanese surgeons were asked to complete a questionnaire pertaining to their experience and the time taken to perform the frontal dissection was recorded. The course was streamed to over 200 otolaryngologists worldwide.

Results: All dissectors completed five frontal sinusotomies. The time to identify the frontal sinus drainage pathway (FSDP) significantly reduced from 1,292 ± 672 to 321 ± 267 s (p = 0.02), despite an increase in the difficulty of the frontal recess anatomy. Image analysis revealed the volume of FSDP was improved (2.36 ± 0.00 to 9.70 ± 1.49 ml, p = 0.014). Questionnaires showed the course's general benefit was 95.47 ± 5.13 in dissectors and 89.24 ± 15.75 in audiences.

Conclusion: The combination of telemedicine software, web-conferencing technology, standardized 3D sinus models, and expert supervision, provides excellent training outcomes for surgeons in circumstances when classical surgical workshops cannot be realized.

Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa.
Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Kazuhiro Ogi, Alkis J Psaltis, Yuji Nakamaru, Akihiro Homma, Peter-John Wormald, Sarah Vreugde
Auris, nasus, larynx, 48, 5, 890, 897, 2021年10月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Recently, depleted tissue zinc levels were found in nasal mucosa from patients with chronic rhinosinusitis (CRS) in correlation with tissue eosinophilia, however, no clinical biomarkers for tissue zinc levels have been identified. Metallothionein-3 (MT3) is an intracellular zinc chelator and previous data showed MT3 mRNA levels to be reduced in CRS patients with nasal polyps (CRSwNP). In this study, we examined the correlation between MT3 expression and zinc levels in nasal mucosa and primary human nasal epithelial cells (HNECs) to investigate whether MT3 could be a clinical biomarker for tissue zinc levels. METHOD: Tissue was harvested from 36 patients and mounted on tissue micro-array (TMA) slides. MT3 expression and tissue zinc fluorescence intensity were measured at different areas within the mucosa (surface epithelium and lamina propria) and compared between controls, CRSwNP and CRS without nasal polyps (CRSsNP) patients. MT3 mRNA and protein expression were examined in zinc-depleted HNECs by qPCR and immunofluorescence microscopy. RESULTS: MT3 expression in CRSwNP was significantly decreased in both surface epithelium (p<0.001 to controls) and lamina propria (p = 0.0491 to controls). There was a significant positive correlation between tissue zinc levels and MT3 expression in nasal mucosa (r = 0.45, p = 0.007). In zinc-deplete HNECs, MT3 expression was significantly decreased at mRNA (p = 0.02) and protein level (p<0.01). There was a significant positive correlation between tissue zinc levels and MT3 expression within individual HNECs (r = 0.59, p<0.001). CONCLUSIONS: MT3 expression reflects intramucosal zinc levels in both nasal mucosa and HNECs indicating MT3 could be used as a clinical biomarker for monitoring intracellular zinc levels in the nasal mucosa.

Notch Signaling in Acquired Middle Ear Cholesteatoma.
Atsushi Fukuda, Satoshi Kano, Yuji Nakamaru, Shinya Morita, Kimiko Hoshino, Keishi Fujiwara, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 42, 9, e1389-e1395, 2021年10月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, HYPOTHESIS: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. BACKGROUND: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. METHODS: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler™ PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. RESULTS: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 ± 32.4% and 44.9 ± 17.8%, respectively) were significantly lower than in the EAC skin (83.4 ± 17.5% and 55.7 ± 7.1%, respectively) (p < 0.001 and p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 ± 11.4%) was significantly higher than in the EAC skin (0.5 ± 0.7%) (p < 0.001). CONCLUSION: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.

鼻中隔前彎の客観的評価と適切な鼻中隔矯正術の術式選択　　　　　　　　　　　　　　　
木村 将吾, 中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 本間 明宏
日本鼻科学会会誌, 60, 3, 312, 312, (一社)日本鼻科学会, 2021年09月
日本語

鼻粘膜上皮細胞におけるTLR3依存性自然免疫シグナル　　　　　　　　　　　　　　　
鈴木 正宣, 中丸 裕爾, 中薗 彬, 本間 あや, 木村 将吾, Sarah Vreugde, Wormald PJ, 本間 明宏
日本鼻科学会会誌, 60, 3, 352, 352, (一社)日本鼻科学会, 2021年09月
日本語

Characteristics of and Prognosis for Facial Palsy in Patients With Otitis Media With ANCA-Associated Vasculitis (OMAAV).
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Yasushi Furuta, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 42, 10, e1577-e1582, 2021年08月04日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of the present study was to investigate the characteristics and prognosis of facial palsy in patients with otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Thirty-seven patients with OMAAV. MAIN OUTCOME MEASURES: The patients were divided into the facial palsy group and non-palsy group. The severity of and prognosis for facial palsy were evaluated using the House-Brackmann facial grading system (HB). Characteristics were compared between the facial palsy group and non-palsy group. RESULTS: Facial palsy was observed in eight patients. The last HB grade for all patients was either grade I or II after treatment with a combination of corticosteroids and immunosuppressant therapy. There were no cases in which palsy relapsed. Facial palsy in OMAAV was significantly more common in female patients, and patients with facial palsy demonstrated significantly higher rates of hypertrophic pachymeningitis than did those without facial palsy. CONCLUSIONS: Facial palsy in patients with OMAAV was detected in 21.6% and a good prognosis was obtained by use of the appropriate treatment. Facial palsy is one of the most important symptoms by which to diagnose OMAAV. When encountering the patients with intractable otitis media complicated with facial palsy, appropriate examination including ANCA titer should be performed.

The clinical features of intractable allergic rhinitis based on a questionnaire administered to clinicians.
Yoshimasa Imoto, Masafumi Sakashita, Masaki Hayama, Yuji Nakamaru, Masanobu Suzuki, Yui Miyabe, Takechiyo Yamada, Hidekazu Saito, Syuji Yonekura, Kenji Kondo, Takaya Higaki, Kayoko Kawashima, Mitsuyoshi Urashima, Shigeharu Fujieda
Allergology international : official journal of the Japanese Society of Allergology, 70, 3, 373, 375, 2021年07月, ［査読有り］, ［国際誌］
英語

当科におけるアブミ骨手術症例の検討　　　　　　　　　　　　　　　
小林 諒, 福田 篤, 藤原 圭志, 中丸 裕爾, 本間 明宏
耳鼻咽喉科臨床 補冊, 補冊157, 65, 65, 耳鼻咽喉科臨床学会, 2021年06月
日本語

4剤の生物学的製剤を使用し上下気道の反応性の違いを観察し得た重症喘息の1例
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
アレルギー, 70, 4, 315, 320, (一社)日本アレルギー学会, 2021年06月
日本語, 現在,重症喘息の治療には4種類の生物学的製剤が使用可能である.その薬剤選択においては,各種2型炎症関連バイオマーカーの測定値,及び好酸球性副鼻腔炎,アレルギー性鼻炎,アトピー性皮膚炎などの併存疾患の有無を考慮すべきと言われている.今回,好酸球性副鼻腔炎,好酸球性中耳炎を合併し,結果的に4種類の生物学的製剤を使用し,上・下気道それぞれの反応性の違いを観察しえた重症喘息の1症例を経験した.4剤の使い分けに関する明確なアルゴリズムは確立されていない現状を鑑み,生物学的製剤による総合的な治療戦略を考える上で意義が大きいと考え,報告する.(著者抄録)

4剤の生物学的製剤を使用し上下気道の反応性の違いを観察し得た重症喘息の1例
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
アレルギー, 70, 4, 315, 320, (一社)日本アレルギー学会, 2021年06月
日本語

Objective evaluation of caudal deviation of the nasal septum and selection of the appropriate septoplasty technique.
Shogo Kimura, Masanobu Suzuki, Aya Honma, Akira Nakazono, Masayuki Osawa, Yuji Nakamaru, Akihiro Homma
Auris, nasus, larynx, 49, 1, 67, 76, 2021年05月06日, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Several methods have been reported to correct caudal deviation of the nasal septum, including open septorhinoplasty (OSR) and septoplasty with Killian incision (KI). In general, OSR is applied instead of KI for caudal deviation. However, there is little objective evidence own on the effects of OSR and KI for caudal deviation. In this study, we compared surgical outcomes between OSR and KI by quantifying nasal septum deviation using two simple and objective parameters on routine paranasal sinus CT scans. METHODS: We retrospectively analyzed 18 patients who underwent OSR and 11 patients who underwent septoplasty with KI between April 2006 and October 2019. Caudal deviation was defined on the basis of the "Anterior-posterior Position of the most deviated point of the nasal septum (AP)," which was measured on computerized tomography. The deformation rate (DR) of the nasal septum was also calculated. Nasal airway resistance and visual analogue scale (VAS) score for nasal obstruction were examined. RESULTS: The AP was significantly correlated with the VAS score (r=-0.58, p=0.017). The DR in patients with caudal septal deviation was significantly decreased by OSR (0.14±0.06 to 0.03±0.03, p=0.004), but not by KI (0.09±0.08 to 0.04±0.03, p=0.25). OSR also improved nasal airway resistance (1.10±0.44 to 0.42±0.15, p=0.02), and the VAS score (79.11±14.74 to 5.78±7.89, p=0.004). CONCLUSION: Nasal obstruction is more severe in patients with the caudal deviation. OSR corrects caudal deviation of the nasal septum more effectively than does KI. The AP could be useful for the evaluation of the deviation of the nasal septum and help in selecting the appropriate septoplastic technique.

Psychological evaluation for patients with non-cured facial nerve palsy.
Keishi Fujiwara, Atsushi Fukuda, Shinya Morita, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Yasushi Furuta, Akihiro Homma
Auris, nasus, larynx, 49, 1, 53, 57, 2021年05月04日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: The aim of the present study was to evaluate the psychological condition of patients with non-cured facial nerve palsy and to investigate whether their psychological condition is correlated with the degree of facial nerve palsy, synkinesis or quality of life. METHODS: Thirty patients with non-cured facial nerve palsy were enrolled in this study. Psychological conditions were evaluated by questionnaires including State-Trait Anxiety Inventory and Self-rating Depression Scale. RESULTS: Of the thirty patients with non-cured facial nerve palsy, 17 (56.7%) and 15 patients (50.0%) felt anxiety and depression, respectively. Although there were no significant correlations between their psychological condition and the degree of facial nerve palsy or that of sequelae, significant correlations were observed between psychological condition and the degree of QOL, especially in terms of social function. CONCLUSIONS AND SIGNIFICANCE: Disabilities associated with facial nerve palsy may be overlooked when evaluation is performed by physician-graded instruments alone. To resolve this problem, patients with non-cured facial nerve palsy should be evaluated by not only physician-graded tools but also patient-based assessment tools.

鼻腔粘膜上皮細胞における新型コロナウィルス細胞侵入因子の発現制御機構　　　　　　　　　　　　　　　
中薗 彬, 鈴木 正宣, 木村 将吾, 本間 あや, 中丸 裕爾, Ramezanpour Mahnaz, Vreugde Sarah, Wormald P.J., 本間 明宏
日本耳鼻咽喉科免疫アレルギー感染症学会抄録集, 1回, 127, 127, 日本耳鼻咽喉科免疫アレルギー感染症学会, 2021年05月
日本語

Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases.
Masanobu Suzuki, Takayoshi Suzuki, Masashi Watanabe, Shigetsugu Hatakeyama, Shogo Kimura, Akira Nakazono, Aya Honma, Yuji Nakamaru, Sarah Vreugde, Akihiro Homma
Allergology international : official journal of the Japanese Society of Allergology, 70, 2, 190, 200, 2021年04月, ［査読有り］, ［責任著者］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Zinc is an essential micronutrient in human body and a vital cofactor for the function of numerous proteins encoded by the human genome. Zinc has a critical role in maintaining many biochemical and physiological processes at the molecular, cellular, and multiple organ and systemic levels. The alteration of zinc homeostasis causes dysfunction of many organs and systems. In the immune system, zinc regulates the differentiation, proliferation and function of inflammatory cells, including T cells, eosinophils, and B cells, by modifying several signaling pathways such as NFκB signaling pathways and TCR signals. An adequate zinc level is essential for proper immune responses and decreased zinc levels were reported in many allergic inflammatory diseases, including atopic dermatitis, bronchial asthma, and chronic rhinosinusitis. Decreased zinc levels often enhance inflammatory activation. On the other hand, the inflammatory conditions alter the intracellular homeostasis of zinc, often decreasing zinc levels. These findings implied that there could be a vicious cycle between zinc deficiency and inflammatory conditions. In this review, we present recent evidence on the involvement of zinc in atopic dermatitis, bronchial asthma, and chronic rhinosinusitis, with insights into the involvement of zinc in the underlying molecular and cellular mechanisms related to these allergic inflammatory diseases.

Usefulness of the Video Head Impulse Test for the Evaluation of Vestibular Function in Patients With Otitis Media With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 42, 4, e483-e488, 2021年04月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To investigate usefulness of the video Head Impulse Test (vHIT) as a method for evaluating semicircular canal function in patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Fourteen patients with OMAAV underwent vestibular examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex (VOR) and the presence of catch-up saccade were examined for each semicircular canal. RESULTS: Seven (50.0%) of the 14 patients felt subjective symptoms of disequilibrium. Dysfunction in at least one semicircular canal was detected in all ears of the OMAAV patients evaluated by vHIT. Dysfunction in posterior semicircular canal was detected more frequently than that in the anterior or horizontal canal. There were no significant correlations between the gain in VOR and hearing loss. CONCLUSIONS: vHIT is thought to be the most suitable method for evaluating semicircular canal function in patients with OMAAV as vHIT is not influenced by middle ear pathology and was able to evaluate vertical canal function including the posterior canal.

Prognostic factors for duration of vertigo after stapes surgery via a time-to-event analysis.
Atsushi Fukuda, Keishi Fujiwara, Shinya Morita, Kimiko Hoshino, Hiroko Yanagi, Yuji Nakamaru, Akihiro Homma
Acta oto-laryngologica, 141, 3, 216, 221, 2021年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Vertigo or dizziness after stapes surgery occurs sometimes, and it is generally temporary. However, while rare, it can be prolonged. AIMS/OBJECTIVES: To investigate the prognostic factors for duration of vertigo following stapedotomy using a time-to-event analysis. MATERIALS AND METHODS: The present study included a total of 35 primary ears (26 with otosclerosis and nine with congenital stapes fixation) from 31 patients. We assessed residual rates of nystagmus and complaints of subjective vestibular symptoms using Kaplan-Meier time-to-event methods. RESULTS: Postoperative spontaneous nystagmus was observed in 23 (65.7%) ears, and postoperative subjective vestibular symptoms were confirmed in 27 (77.1%) ears. The total mean duration of postoperative spontaneous nystagmus and subjective vestibular symptoms was 9.8 (range: 0-158) and 33.9 days (0-732), respectively. A history of stapes surgery in the opposite ear was a significant predictive factor for prolonged nystagmus and subjective vestibular symptoms (p = .0059 and p = .0146). CONCLUSIONS AND SIGNIFICANCE: For individuals with a history of stapes surgery in the opposite ear, spontaneous nystagmus and vertigo/dizziness sensations following stapedotomy may persist for a longer duration than in those without a history of stapes surgery in the opposite ear.

The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.
Yuji Nakamaru, Masanobu Suzuki, Satoshi Kano, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Rikiya Onimaru, Koichi Yasuda, Hiroki Shirato, Akihiro Homma
Auris, nasus, larynx, 48, 1, 131, 137, 2021年02月, ［査読有り］, ［筆頭著者, 責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: Despite of rapid advances in endoscopic surgery, the gold standard for sinonasal squamous cell carcinoma (SNSCC) surgery has remained the open approach with en-block resection due to the aggressive nature of SNSCC, including frequent recurrence and high mortality rate. For that reason, few studies have focused on SNSCC treated by endoscopic surgery alone. The objective of this study was to evaluate the usefulness of endoscopic surgery for patients with SNSCC. METHODS: A retrospective analysis was performed for 15 consecutive SNSCC patients who underwent endoscopic surgery without an open approach. We carefully selected patients whose tumor attachment sites could be fully visualized and completely resected through an endonasal approach. RESULTS: Of the fifteen patients, 4 patients (27%) were diagnosed with T1, 7 (47%) with T2, 4 (27%) with T3, and no patients with T4a or T4b disease. Four of the 15 (27%) patients showed positive surgical margins. The 5-yr overall survival, disease-specific survival, and local control rate was 72.4%, 79.6%, and 92.9%, respectively. The 5-yr disease-specific survival for T1, T2, and T3 disease was 100% and 75% and 75%, respectively. Patients with negative surgical margins had a better disease-specific survival rate than did those with positive surgical margins (p = 0.0253). CONCLUSION: Endoscopic surgery for patients with SNSCC appears to afford an effective method in selected cases. The achievement of negative surgical margins with a good view of the tumor attachment site was considered to be critical to the management of SNSCC.

Endonasal endoscopic surgery for sinonasal squamous cell carcinoma from an oncological perspective.
Akihiro Homma, Yuji Nakamaru, Valerie J Lund, Ehab Y Hanna, Luiz Paulo Kowalski, Ronaldo Nunes Toledo, Antti A Mäkitie, Juan Pablo Rodrigo, Alessandra Rinaldo, Carl H Snyderman, Alfio Ferlito
Auris, nasus, larynx, 48, 1, 41, 49, 2021年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Endonasal endoscopic surgery (EES) has been applied to the management of sinonasal (SN) tumors based on recent advances in endoscopic surgical techniques and technologies over the past three decades. EES has been mainly indicated for benign tumors and less aggressive malignant tumors. Notwithstanding this, EES has been gradually adopted for squamous cell carcinoma (SCC), which is the most common histology among SN malignancies. However, an analysis of the outcomes of EES for patients with SCC is difficult because most articles included SCC a wide range of different tumor histologies. Therefore, we herein review and clarify the current status of EES focusing on SCC from an oncological perspective. The oncologic outcomes and the ability to achieve a histologically complete resection are similar between endoscopic and open approaches in highly selected patients with SN-SCC. Surgical complications associated with EES are likely similar for SN-SCC compared to other sinonasal malignancies. The indications for a minimally invasive approach such as EES in the management of patients with SN-SCC should be stricter than those for less aggressive malignant tumors because of the aggressive nature of SCC. Also, it is important to achieve negative surgical margins with EES in patients with SCC. We believe that the indications for EES for SN-SCC are widening due to advances in diagnostic imaging, and endoscopic surgical techniques and technologies. However, while expanding the indications for EES for SN-SCC we must carefully confirm that the outcomes support this strategy.

TLR Signals in Epithelial Cells in the Nasal Cavity and Paranasal Sinuses.
Masanobu Suzuki, Clare Cooksley, Takayoshi Suzuki, Mahnaz Ramezanpour, Akira Nakazono, Yuji Nakamaru, Akihiro Homma, Sarah Vreugde
Frontiers in allergy, 2, 780425, 780425, 2021年, ［国際誌］
英語, 研究論文（学術雑誌）, The respiratory tract is constantly at risk of invasion by microorganisms such as bacteria, viruses, and fungi. In particular, the mucosal epithelium of the nasal cavity and paranasal sinuses is at the very forefront of the battles between the host and the invading pathogens. Recent studies have revealed that the epithelium not only constitutes a physical barrier but also takes an essential role in the activation of the immune system. One of the mechanisms equipped in the epithelium to fight against microorganisms is the Toll-like receptor (TLR) response. TLRs recognize common structural components of microorganisms and activate the innate immune system, resulting in the production of a plethora of cytokines and chemokines in the response against microbes. As the epithelia-derived cytokines are deeply involved in the pathogenesis of inflammatory conditions in the nasal cavity and paranasal sinuses, such as chronic rhinosinusitis (CRS) and allergic rhinitis (AR), the molecules involved in the TLR response may be utilized as therapeutic targets for these diseases. There are several differences in the TLR response between nasal and bronchial epithelial cells, and knowledge of the TLR signals in the upper airway is sparse compared to that in the lower airway. In this review, we provide recent evidence on TLR signaling in the upper airway, focusing on the expression, regulation, and responsiveness of TLRs in human nasal epithelial cells (HNECs). We also discuss how TLRs in the epithelium are involved in the pathogenesis of, and possible therapeutic targeting, for CRS and AR.

Comparison of clinical characteristics of the nasal manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) and eosinophilic chronic rhinosinusitis (ECRS).
Masanobu Suzuki, Akira Nakazono, Shinya Morita, Atsushi Fukuda, Aya Honma, Takayoshi Suzuki, Shogo Kimura, Yuji Nakamaru, Akihiro Homma
Allergology international : official journal of the Japanese Society of Allergology, 70, 1, 143, 144, 2021年01月, ［査読有り］, ［責任著者］, ［国際誌］
英語

Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells.
Akira Nakazono, Yuji Nakamaru, Mahnaz Ramezanpour, Takeshi Kondo, Masashi Watanabe, Shigetsugu Hatakeyama, Shogo Kimura, Aya Honma, P J Wormald, Sarah Vreugde, Masanobu Suzuki, Akihiro Homma
Frontiers in cellular and infection microbiology, 11, 655666, 655666, 2021年, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: From the first detection in 2019, SARS-CoV-2 infections have spread rapidly worldwide and have been proven to cause an urgent and important health problem. SARS-CoV-2 cell entry depends on two proteins present on the surface of host cells, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). The nasal cavity is thought to be one of the initial sites of infection and a possible reservoir for dissemination within and between individuals. However, it is not known how the expression of these genes is regulated in the nasal mucosa. Objective: In this study, we examined whether the expression of ACE2 and TMPRSS2 is affected by innate immune signals in the nasal mucosa. We also investigated how fluticasone propionate (FP), a corticosteroid used as an intranasal steroid spray, affects the gene expression. Methods: Primary human nasal epithelial cells (HNECs) were collected from the nasal mucosa and incubated with Toll-like receptor (TLR) agonists and/or fluticasone propionate (FP), followed by quantitative PCR, immunofluorescence, and immunoblot analyses. Results: Among the TLR agonists, the TLR3 agonist Poly(I:C) significantly increased ACE2 and TMPRSS2 mRNA expression in HNECs (ACE2 36.212±11.600-fold change, p<0.0001; TMPRSS2 5.598±2.434-fold change, p=0.031). The ACE2 protein level was also increased with Poly(I:C) stimulation (2.884±0.505-fold change, p=0.003). The Poly(I:C)-induced ACE2 expression was suppressed by co-incubation with FP (0.405±0.312-fold change, p=0.044). Conclusion: The activation of innate immune signals via TLR3 promotes the expression of genes related to SARS-CoV2 cell entry in the nasal mucosa, although this expression is suppressed in the presence of FP. Further studies are required to evaluate whether FP suppresses SARS-CoV-2 viral cell entry.

[A CASE OF SEVERE ASTHMA WHO REQUIRED A SWITCH OF FOUR BIOLOGICS: DIFFERENTIAL RESPONSES ON UPPER AND LOWER AIRWAYS].
Machiko Matsumoto Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Yuji Nakamaru, Satoshi Konno
Arerugi = [Allergy], 70, 4, 315, 320, 2021年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, At the time of writing of this manuscript, four biologics were clinically available for treatment against severe asthma. The choice of four biologics has been taking into account of the results of several type 2 inflammationrelated biomarkers, and the comorbidities of asthma, such as eosinophilic chronic rhinosinusitis, allergic rhinitis, and atopic dermatitis.In this study, we have experienced a case of severe asthma complicated by eosinophilic chronic rhinosinusitis and eosinophilic otitis media, resulting in the use of four biologics, and we observed differential response of upper and lower airways. As a clear algorithm has not been established for the use of four biologics, our experience of this case would provide important lesson for considering the therapeutic strategies against severe asthma.

Zinc-depletion associates with tissue eosinophilia and collagen depletion in chronic rhinosinusitis.
M Suzuki, M Ramezanpour, C Cooksley, T J Lee, B Jeong, S Kao, T Suzuki, A J Psaltis, Y Nakamaru, A Homma, P J Wormald, S Vreugde
Rhinology, 58, 5, 451, 459, 2020年10月01日, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro. METHODOLOGY: Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts. RESULTS: CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion. CONCLUSIONS: These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.

video Head Impulse Testを用いたOMAAV症例の半規管機能評価
藤原 圭志, 柳 紘子, 森田 真也, 干野 季美子, 福田 篤, 中丸 裕爾, 本間 明宏
日本耳鼻咽喉科学会会報, 123, 4, 1142, 1142, (一社)日本耳鼻咽喉科頭頸部外科学会, 2020年09月
日本語

ベンラリズマブ不応後にメポリズマブへ変更した難治性喘息の1例
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 中丸 裕爾, 今野 哲
アレルギー, 69, 8, 678, 682, (一社)日本アレルギー学会, 2020年09月
日本語, 症例は66歳の好酸球性副鼻腔炎を合併した難治性喘息患者.ベンラリズマブ開始後,喘息症状は著明に改善し,末梢血好酸球数は0/μlとなり,月に数回程度使用していた頓用の経口ステロイドも不要となった.しかし,投与開始後7ヵ月目で喘息症状は再燃し,好酸球数は813/μlと増加したため,メポリズマブへ変更したところ,喘息症状に加え鼻症状も改善した.以上の経過からベンラリズマブに対する中和抗体が産生された可能性が考えられた.中和抗体は日常臨床において測定できないため,中和抗体産生に関する症例報告は認めない.本症例においても疑いにとどまるが,臨床経過からはその可能性は高い.また本症例の鼻症状はベンラリズマブへは反応が乏しく,メポリズマブで改善した.生物学的製剤の臓器における治療反応性の違いも重要な観点である.以上から,本症例は生物学的製剤の特色を多面的に反映した経過を示し,報告の価値は高い.(著者抄録)

頭頸部粘膜悪性黒色腫に対する術後陽子線治療30GyE/5回の初期経験　　　　　　　　　　　　　　　
湊川 英樹, 安田 耕一, 出倉 康裕, 鈴木 正宣, 中丸 裕爾, 中薗 彬, 鈴木 崇祥, 対馬 那由多, 加納 里志, 鬼丸 力也, 清水 伸一, 本間 明宏, 青山 英史
頭頸部癌, 46, 2, 188, 188, (一社)日本頭頸部癌学会, 2020年07月
日本語

Preoperative Pulmonary Function Testing to Predict Recurrence of Chronic Rhinosinusitis With Nasal Polyps
Yuji Nakamaru, Masanobu Suzuki, Aya Honma, Akira Nakazono, Shogo Kimura, Keishi Fujiwara, Shinya Morita, Satoshi Konno, Akihiro Homma
ALLERGY & RHINOLOGY, 11, SAGE PUBLICATIONS INC, 2020年07月, ［査読有り］, ［筆頭著者, 責任著者］
英語, 研究論文（学術雑誌）, Background: Although the close relationship between the upper and lower airways has been highlighted previously, little is known about the association between lung function and the recurrence of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the factors associated with pulmonary function that affect CRSwNP recurrence after surgery.Methods: We performed a series of routine pulmonary function tests for general anesthesia prior to CRSwNP surgery. The values for each parameter were compared in the presence or absence of recurrence.Results: Sixty-nine patients with CRSwNP were included. The percent predicted forced expiratory volume in one second (%FEV1) in the recurrent group was significantly lower than that in the non-recurrent group (P = .005). A multivariable logistic regression model revealed that %FEV1 was a positive predictor of recurrence (odds ratio: 0.96, 95% CI: 0.92-0.99, P = .023). There were no significant differences in the other pulmonary functions between the two groups.Conclusions: We found that %FEV1 may be a predictor of CRSwNP recurrence after surgery. As %FEV1 is a pulmonary function test that is routinely performed before surgery, this parameter is readily applicable. Moreover, as %FEV1 appears to have the potential to reveal concealed asthma, %FEV1 might be a particularly useful tool for the prediction of CRSwNP recurrence after surgery.

Evaluation of Semicircular Canal Function by Video Head Impulse Test in Patients With Facial Nerve Schwannoma.
Keishi Fujiwara, Shinya Morita, Yasushi Furuta, Hiroko Yanagi, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 41, 5, e615-e622, 2020年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of the present study was to evaluate semicircular canal function by video Head Impulse Test (vHIT) in patients with facial nerve schwannoma (FNS). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Seven patients with FNS underwent vHIT examination. MAIN OUTCOME MEASURES: The gain in vestibulo-ocular reflex and the presence of catch-up saccade were examined for the semicircular canals including the vertical canals. RESULTS: Dysfunction of the semicircular canals was detected by vHIT in three of seven cases. Nystagmus beating toward the non-affected side was observed in all three cases with semicircular canal dysfunction. Dysfunction was observed in a case with no direct compression of the vestibular nerve or semicircular canals by FNS. CONCLUSIONS: Semicircular canal function in patients with FNS could be evaluated by vHIT. vHIT has two advantages for the evaluation of vestibular function in patients with FNS. First, vHIT could be used for the patients in whom a tumor exists in the external auditory canal or middle ear, unlike caloric testing. Second, as vHIT could evaluate all three canals, impaired vestibular nerves could be speculated from vHIT results when a tumor exists in internal auditory canal. vHIT should be performed in patients with FNS, especially before surgery, to evaluate vestibular function.

Rosai-Dorfman disease: earlier spontaneous regression of skin lesions relative to nasal, pharyngeal, and bone lesions.
Kazumasa Sato, Hideyuki Ujiie, Shinichi Nakazato, Mika Watanabe, Erika Watanabe, Teruki Yanagi, Yuji Nakamaru, Dai Takagi, Ryuta Arai, Tomohiro Onodera, Takeshi Kondo, Takanori Teshima, Hiroshi Shimizu
European journal of dermatology : EJD, 30, 2, 182, 183, 2020年04月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Analysis of semicircular canal function as evaluated by video Head Impulse Test in patients with vestibular schwannoma.
Keishi Fujiwara, Shinya Morita, Atsushi Fukuda, Hiroki Akamatsu, Hiroko Yanagi, Kimiko Hoshino, Yuji Nakamaru, Satoshi Kano, Akihiro Homma
Journal of vestibular research : equilibrium & orientation, 30, 2, 101, 108, 2020年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: The aim of the present study was to investigate the factors influencing semicircular canal function as evaluated by video Head Impulse Test (vHIT) in patients with vestibular schwannoma. METHODS: Twenty-four patients with untreated vestibular schwannoma underwent vHIT examination. The correlations between semicircular canal function and factors including age, tumor size, disease duration and hearing loss were evaluated. RESULTS: The functions of all three semicircular canals on the affected side evaluated by vHIT were significantly lower than those on the unaffected side. Although there were no significant correlations between semicircular canal function and age, tumor size or disease duration, a negative significant correlation between vestibulo-ocular reflex (VOR) gain as evaluated by vHIT and hearing loss was observed. CONCLUSIONS: From the results of the relationship between hearing loss and VOR gain, the damage to the audio and vestibular systems in patients with VS may be correlated. As it has been suggested that tumor size was not a significant factor in the VOR gain evaluated by vHIT, multifactorial causes rather than the simple compression of the vestibular nerves alone may be related to the dysfunction of the semicircular canals in patients with vestibular schwannoma.

[A CASE OF SEVERE ASTHMA SWITCHED TO MEPOLIZUMAB DUE TO LATE-OCCURRING UNRESPONSIVENESS TO BENRALIZUMAB].
Machiko Matsumoto-Sasaki, Kaoruko Shimizu, Masanobu Suzuki, Masaru Suzuki, Yuji Nakamaru, Satoshi Konno
Arerugi = [Allergy], 69, 8, 678, 682, 2020年, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, We report the case of a 66-year-old patient with severe asthma complicated by eosinophilic chronic rhinosinusitis (ECRS). The patient was initially treated with benralizumab, which resulted in marked improvement of asthma symptoms and reduced the peripheral blood eosinophil count to 0/μL. Additionally, oral steroids were discontinued. After 7 months of benralizumab administration, the asthma symptoms worsened and peripheral blood eosinophil count increased to 813/μL. The neutralizing antibodies to benralizumab may have resulted in the recurrence of symptoms due to eosinophilic inflammation. The nasal symptoms, on which benralizumab had an unremarkable effect, improved when treatment was switched to mepolizumab. However, the difference in effects of biologics on ECRS has not been elucidated and warrants further investigation. To the best of our knowledge, this is the first report of a case of severe asthma in which mepolizumab administration reversed the clinical deterioration of asthma, which was possibly caused by neutralizing antibodies to benralizumab.

好酸球性中耳炎(EOM)と中耳炎を合併した好酸球性多発血管炎性肉芽腫症(EGPA)の比較　　　　　　　　　　　　　　　
福田 篤, 森田 真也, 藤原 圭志, 干野 季美子, 中丸 裕爾, 本間 明宏
日本耳科学会総会・学術講演会抄録集, 29回, 508, 508, (一社)日本耳科学会, 2019年10月
日本語

当科における局所進行外耳道扁平上皮癌の治療成績の検討
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 対馬 那由多, 鈴木 崇祥, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 45, 3, 300, 304, (一社)日本頭頸部癌学会, 2019年10月
日本語, 我々は、局所進行外耳道扁平上皮癌に対する治療成績、特にドセタキセル、シスプラチン、5-FUの併用(TPF)の化学療法同時併用放射線療法(CCRT)の治療成績と安全性、および腫瘍の進展範囲と予後との関係を検討した。対象は当科で根治治療を行った外耳道癌扁平上皮癌で、ピッツバーグ分類のT3-4の21症例とした。その結果、硬膜と顎関節への進展が頸部転移と相関を示し、顎関節への進展が局所再発と相関を示した。全症例の2年粗生存率(OS)は61.1%、2年局所制御率(LC)は52.1%であった。CCRT症例では、TPF併用の2年OSは85.7%、それ以外では25.0%、TPF併用の2年LCは57.1%、それ以外では25.0%であった。また、TPF併用CCRTにおけるG3以上の白血球減少は55%、好中球減少は45%であった。TPF併用のCCRTは局所進行外耳道扁平上皮癌に対して高い有効性と安全性を示した。(著者抄録)

【二次出版】ANL Secondary Publication 急性感音難聴患者における抗ムンプスIgM抗体陽性率 北海道における後向き多施設共同研究
福田 篤, 森田 真也, 中丸 裕爾, 干野 季美子, 藤原 圭志, 赤澤 茂, 坂下 智博, 小原 修幸, 本間 明宏
日本耳鼻咽喉科学会会報, 122, 9, 1267, 1268, (一社)日本耳鼻咽喉科学会, 2019年09月
日本語

当院における外鼻形成術および鼻中隔矯正術施行例の検討　　　　　　　　　　　　　　　
木村 将吾, 中丸 裕爾, 鈴木 正宣, 本間 あや, 中薗 彬, 本間 明宏
日本鼻科学会会誌, 58, 3, 632, 632, (一社)日本鼻科学会, 2019年09月
日本語

Differentiation Between Eosinophilic Otitis Media and Otitis Media Associated With Eosinophilic Granulomatosis With Polyangiitis.
Atsushi Fukuda, Shinya Morita, Yuji Nakamaru, Kimiko Hoshino, Keishi Fujiwara, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 40, 8, e796-e802, 2019年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To perform comparisons and clarify differences in clinical manifestations between eosinophilic otitis media (EOM) and otitis media associated with eosinophilic granulomatosis with polyangiitis (EGPA). STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Twenty-two ears of 11 patients exhibiting EOM (EOM group) and 20 ears of 12 patients exhibiting otitis media associated with EGPA (EGPA group). MAIN OUTCOME MEASURES: Otological manifestations, nasal and paranasal manifestations, incidence of asthma, positivity for serum antineutrophil cytoplasmic antibodies (ANCA), total serum immunoglobulin (Ig) E level, peripheral blood eosinophil fraction, and hearing outcomes. RESULTS: The incidence and age of onset of asthma and chronic rhinosinusitis were comparable between the EOM and EGPA groups. Moreover, otological findings and hearing outcomes at the initial visit were similar in both groups. Computed tomography images of the paranasal sinus showed predominant opacification of the ethmoid sinus in both groups. Although the total serum IgE level was not significantly different, the peripheral blood eosinophil fraction was significantly larger in the EGPA group than in the EOM group (p = 0.0035). Furthermore, the rate of myeloperoxidase-antineutrophil cytoplasmic antibodies (ANCA) positivity was significantly higher in the EGPA group than in the EOM group (p = 0.019). CONCLUSIONS: The findings of the present study suggest that the phenotypic characteristics of EOM closely resemble those of otitis media associated with EGPA in early stages before the appearance of vasculitis. Therefore, it is challenging to differentiate the two conditions purely on the basis of otorhinological examinations.

Make-Up Therapy for Patients With Facial Nerve Palsy.
Keishi Fujiwara, Yasushi Furuta, Wakae Aoki, Yuji Nakamaru, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Akihiro Homma
The Annals of otology, rhinology, and laryngology, 128, 8, 721, 727, 2019年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To investigate the effectiveness of make-up therapy for patients with facial nerve palsy. METHODS: Seven female patients with facial nerve palsy who received specialist make-up therapy were enrolled. The objective of the make-up therapy was to obtain a symmetrical facial appearance. RESULTS: Overall score for the Facial Clinimetric Evaluation (FaCE) scale was significantly improved after make-up therapy. There was a tendency for symptoms of depression to be improved among patients after make-up therapy. CONCLUSION: Make-up therapy to improve the symmetry of facial appearance could afford a noninvasive and low-cost treatment for patients with facial nerve palsy, especially in terms of patient quality of life and psychological condition.

ANCA関連血管炎性中耳炎における好中球細胞外トラップの測定と臨床応用
森田 真也, 中丸 裕爾, 鈴木 正宣, 本間 明宏
耳鼻咽喉科免疫アレルギー, 37, 2, 77, 78, 日本耳鼻咽喉科免疫アレルギー学会, 2019年06月
日本語

好酸球性中耳炎EOMと中耳炎を合併した好酸球性多発血管炎性肉芽腫症EGPAの比較
福田 篤, 森田 真也, 藤原 圭志, 干野 季美子, 中丸 裕爾, 本間 明宏
日本耳鼻咽喉科学会会報, 122, 4, 627, 627, (一社)日本耳鼻咽喉科学会, 2019年04月
日本語

video Head Impulse Testを用いた聴神経腫瘍患者の半規管機能評価
藤原 圭志, 柳 紘子, 森田 真也, 干野 季美子, 福田 篤, 赤松 明樹, 中丸 裕爾, 本間 明宏
日本耳鼻咽喉科学会会報, 122, 4, 704, 704, (一社)日本耳鼻咽喉科学会, 2019年04月
日本語

Short-Term Hearing Prognosis of Ossiculoplasty in Pars Flaccida Cholesteatoma Using the EAONO/JOS Staging System.
Fukuda A, Morita S, Nakamaru Y, Hoshino K, Fujiwara K, Homma A
The journal of international advanced otology, 15, 1, 2, 7, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: The aim of the present study was to investigate the prognostic factors for short-term hearing outcomes of ossiculoplasty for primary pars flaccida cholesteatoma according to the European Academy of Otology and Neurotology/Japanese Otological Society (EAONO/JOS) and 2015 JOS staging systems. MATERIALS AND METHODS: A total of 34 patients with primary pars flaccida cholesteatoma who underwent one-stage tympanomastoidectomy with partial ossicular reconstruction using double cartilage block were included in the study. The postoperative pure-tone average air-bone gap (PTA-ABG) was calculated, and two criteria of successful hearing outcomes were defined as ≤10 and ≤20 dB. Patients were classified according to the EAONO/JOS and 2015 JOS staging systems. Cochran-Armitage test was used to statistically analyze staging, and Fisher's exact test was used to analyze other factors. RESULTS: Successful hearing outcome with postoperative PTA-ABG ≤10 and ≤20 dB occurred in 23.5% and 55.9% of cases, respectively. When postoperative PTA-ABG ≤20 dB was defined as successful, the success rate significantly decreased with increase in EAONO/JOS stage, and S0 pathological status of the stapes (no involvement) was a significantly favorable predictive factor. When postoperative PTA-ABG ≤10 dB was regarded as successful, the significantly favorable predictive factors were S0 pathological status of the stapes and development of mastoid cells with MC2-3 (better developed cells). CONCLUSION: Favorable prognostic factors for hearing outcomes of tympanomastoidectomy with partial ossicular reconstruction for primary pars flaccida cholesteatoma were low stage following the EAONO/JOS staging system and no stapes involvement and better development of mastoid cells following the 2015 JOS staging system.

Evaluation of Vertical Semicircular Canal Function in Patients With Vestibular Schwannoma.
Fujiwara K, Yanagi H, Morita S, Hoshino K, Fukuda A, Nakamaru Y, Homma A
The Annals of otology, rhinology, and laryngology, 128, 2, 113, 120, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES:: The aim of this study was to investigate vertical semicircular canal function in patients with vestibular schwannoma (VS) by video head impulse test (vHIT). METHODS:: Fifteen patients with VS who had not received any treatment, including surgery or stereotactic radiotherapy, before vHIT examination were enrolled. Vestibulo-ocular reflex gain and catch-up saccade in vHIT were evaluated. RESULTS:: Dysfunction of anterior and posterior semicircular canals was detected by vHIT in 26.7% and 60.0%, respectively. Six patients (40.0%) demonstrated abnormalities referable to both vestibular nerve divisions. Abnormalities referable to the superior vestibular nerve were identified in 3 patients (20.0%), while 3 patients (20.0%) demonstrated a pattern indicative of inferior vestibular nerve involvement. Anterior semicircular canal vHIT produced fewer abnormalities than did either horizontal or posterior semicircular canal vHIT. CONCLUSIONS:: Dysfunction of the semicircular canals, including the vertical canals, in patients with VS was detected by vHIT. The anterior semicircular canal was less frequently involved than the horizontal or posterior semicircular canal. The examination of the vertical canals by vHIT is useful in the evaluation of vestibular function in patients with VS.

The Diagnostic and Clinical Utility of the Myeloperoxidase-DNA Complex as a Biomarker in Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.
Shinya Morita, Yuji Nakamaru, Daigo Nakazawa, Masanobu Suzuki, Kimiko Hoshino, Atsushi Fukuda, Fumihiko Hattanda, Kanako Kusunoki, Utano Tomaru, Akihiro Ishizu, Akihiro Homma
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 40, 2, e99-e106, e106, 2019年02月, ［査読有り］, ［責任著者］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: This prospective study aimed to evaluate the diagnostic and clinical utility of the myeloperoxidase (MPO)-DNA complex as a NETosis-derived product in the middle ear fluid of patients with otitis media with antineutrophil cytoplasmic antibody-associated vasculitis (OMAAV). STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. PATIENTS: Twenty-two patients diagnosed with OMAAV. INTERVENTION: Collection of the fluid samples from middle ear. MAIN OUTCOME MEASURE: The levels of the MPO-DNA complex in the fluid samples were quantified using an enzyme-linked immunosorbent assay. RESULTS: Patients with both systemic and localized forms of OMAAV showed significantly higher levels of the MPO-DNA complex compared to the controls (p < 0.001 and p = 0.002, respectively). In particular, they showed significantly higher levels of MPO-DNA complex compared to the controls, regardless of serum antineutrophil cytoplasmic antibody status (p < 0.001 and p < 0.001, respectively) or immunosuppressive therapy (p < 0.001 and p < 0.001, respectively) at the time of sampling. An optical density cutoff value of 0.16 at 405 nm according to the receiver operating characteristic curve showed a sensitivity of 86.4%, specificity of 95.5%, positive predictive value of 95.0% and negative predictive value of 87.5% for the diagnosis of OMAAV. Significant positive correlations were observed between the levels of MPO-DNA complex and the values for air conduction - (r = 0.49, p = 0.022) and bone conduction - pure tone average thresholds (r = 0.45, p = 0.035). CONCLUSIONS: The detection and quantification of the MPO-DNA complex in the otitis media fluid may aid in providing a definite diagnosis as well as predicting the activity and severity of OMAAV.

Spontaneous Regression of Swollen Submandibular Glands in IgG4-Related Disease
Masanobu Suzuki, Yuji Nakamaru, Dai Takagi, Aya Honma, Takayoshi Suzuki, Emi Takakuwa, Shinya Morita, Sarah Vreugde, Akihiro Homma
Allergy & Rhinology, 10, 215265671881673, 215265671881673, SAGE Publications, 2019年01月
研究論文（学術雑誌）, IgG4-related disease is a new clinical entity frequently associated with swelling of the submandibular glands (SMGs). The long-term outcome of SMG swelling without steroid therapy remains unknown.

To examine whether swollen SMGs spontaneously regress without steroid therapy in the context of IgG4-related disease and to identify biomarkers that can predict the spontaneous regression of SMG swelling.

The SMG volume of 49 patients diagnosed with IgG4-related disease was calculated by measuring the axial and coronal planes of computed tomography scans. The change in SMG volume over time was measured and examined by treatment regimen, clinical data, and serum complement level.

We found 28 of 49 (57%) IgG4-related disease patients to have swollen SMGs, with 15 of 20 (75%) of the swollen SMGs regressing without steroid therapy. The time required for the SMGs swelling to regress was significantly shorter in the steroid therapy group than in the no-steroid therapy group. Serum complement components at the initial visit were significantly lower in the regressed SMG group than in the nonregressed SMG group.

We observed 75% of swollen SMGs spontaneously regressed in patients with IgG4-related disease. The time required for the swollen SMGs to regress was longer in patients without steroid therapy than in those with steroid therapy. Serum complement level could be used as a predictor for the spontaneous regression of swollen SMGs in patients with IgG4-related disease.

Treatment outcomes of local advanced external auditory canal squamous cell carcinomas
Satoshi Kano, Shinya Morita, Yuji Nakamaru, Takatsugu Mizumachi, Nayuta Tsushima, Takayoshi Suzuki, Akira Nakazono, Atsushi Fukuda, Koichi Yasuda, Rikiya Onimaru, Hiroki Shirato, Akihiro Homma
Japanese Journal of Head and Neck Cancer, 45, 3, 300, 304, 2019年, ［査読有り］
研究論文（学術雑誌）, © 2019, Japan Society for Head and Neck Cancer. All rights reserved. We analyzed the treatment outcomes and safety of concomitant chemoradiotherapy (CCRT), especially with a combination of docetaxel, cisplatin and 5FU (TPF), for local advanced external auditory canal squamous cell carcinomas. In addition, we analyzed the correlation between tumor invasion site and prognosis. The study comprised 21 patients with the following criteria: (1) external auditory canal squamous cell carcinomas which were subject to radical treatment at Hokkaido University Hospital between 2007 and 2017, and (2) T3–4 classified according to the University of Pittsburg system. As a result, tumor invasion into the dura or temporomandibular joint was associated with neck lymph node metastasis, and tumor invasion into the temporomandibular joint was associated with local recurrence. The 2-year overall survival rate (OS) and 2-year local control rate (LC) were 61.1％ and 52.1％ in all patients, respectively. In patients treated with CCRT, the 2-year OS was 85.7％ in CCRT with TPF and 25.0％ in CCRT with others, and the 2-year LC was 57.1％ in CCRT with TPF and 25.0％ in CCRT with others. Grade 3︲4 leucopenia and neutropenia occurred in 55％ and 45％ of patients treated with CCRT with TPF, respectively. CCRT with TPF shows high efficacy and safety for local advanced external auditory canal squamous cell carcinomas.

Sirtuin-1 Controls Poly (I:C)-Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells.
Suzuki M, Ramezanpour M, Cooksley C, Li J, Nakamaru Y, Homma A, Psaltis A, Wormald PJ, Vreugde S
American journal of respiratory cell and molecular biology, 59, 4, 500, 510, 2018年10月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Matrix metalloproteinase (MMP)-9 is thought to be involved in the etiopathogenesis of chronic rhinosinusitis (CRS) with nasal polyps and cleaves collagen IV, causing hyperpermeability of the basement membrane within mucosal tissue. It is known that MMP-9 expression is negatively affected by sirtuin (SIRT)-1 in human monocytotic cells, retinal endothelial cells, and epithelial carcinoma cells. However, it is unknown which factors affect MMP-9 expression and activity in human nasal epithelial cells (HNECs). To examine factors affecting MMP-9 expression and activity in HNECs, HNECs were stimulated with Toll-like receptor (TLR) agonists, followed by quantitative PCR, immunofluorescence, and zymography to examine MMP-9 expression and activity. MMP-9 expression was evaluated in sinonasal tissue of control subjects without CRS, and patients with CRS without nasal polyps and those with CRS with nasal polyps, in relation to the expression of SIRT1 using a tissue microarray. The effect of SIRT1 stimulation/inhibition on MMP-9 expression in HNECs was also tested. TLR3 agonists increased MMP-9 mRNA expression (473 fold, P = 0.0198) and activity (20.4-fold, P < 0.05). SIRT1 activation or inhibition reciprocally affected MMP-9 expression in the presence of TLR3 agonists. MMP-9 and SIRT1 expression within the epithelial layer of sinonasal tissue was inversely correlated only in patients with CRS but not in control subjects. TLR3 agonists increased MMP-9 expression and activity in HNECs, and the effect was abolished in the presence of SIRT1 activation. SIRT1 and MMP-9 expression was inversely correlated in CRS tissue, supporting SIRT1 as a possible therapeutic target for nasal polyp formation.

Anti-mumps IgM antibody positive rate with sudden sensorineural hearing loss using second-generation enzyme immunoassay: A retrospective, multi-institutional investigation in Hokkaido, Japan
Atsushi Fukuda, Shinya Morita, Yuji Nakamaru, Kimiko Hoshino, Keishi Fujiwara, Shigeru Akazawa, Tomohiro Sakashita, Nobuyuki Obara, Akihiro Homma
Auris Nasus Larynx, 45, 5, 911, 915, Elsevier Ireland Ltd, 2018年10月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: Although elevated anti-mumps IgM antibody levels were reported in 5.7%–7.2% of Japanese patients with sudden sensorineural hearing loss (SSNHL), there were several reports of false-positive cases, such as the continually IgM positive case and the IgM positive case in normal adults. To improve specificity, the new enzyme immuno assay (EIA) anti-mumps IgM antibody measurement kit was introduced in December 2009. This study re-examined the frequency of anti-mumps IgM antibody test positivity with SSNHL using the new measurement kit and compared the results with those from a previous report that used old kit. Methods: This is a retrospective multi-institutional study involving patients diagnosed with SSNHL who exhibited the anti-mumps IgM antibody. We compared the positive rate of anti-mumps IgM antibody and the annual average number of mumps cases per sentinel in Hokkaido between the patients in the present study and patients previously evaluated. Results: Overall, 100 patients with SSNHL were enrolled. One case (1.0%) was positive for anti-mumps IgM antibody. Of the 69 patients evaluated in the previous study, 5 cases (7.2%) were positive for anti-mumps IgM antibody. The positive rate of the anti-mumps IgM antibody in the present cases was significantly lower than that previously reported (p = 0.042). The annual average number of mumps cases per sentinel in Hokkaido of the present and previous surveillance period was 34.47 and 42.77, respectively
no significant difference was seen in these data (p = 0.4519). Conclusion: The present study revealed that 1.0% of SSNHL was positive for the anti-mumps IgM antibody using the new EIA-IgM measurement kit. After the introduction of the new EIA-IgM measurement kit, anti-mumps IgM antibody positive rate with SSNHL significantly decreased, indicating that the proportion of asymptomatic mumps among etiology of SSNHL may be lower than those previously reported.

EAONO/JOS中耳真珠腫進展度分類を用いた術後聴力予後因子の検討　　　　　　　　　　　　　　　
福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 中丸 裕爾, 本間 明宏
Otology Japan, 28, 4, 468, 468, (一社)日本耳科学会, 2018年09月
日本語

vHITを用いた聴神経腫瘍症例の垂直半規管機能評価　　　　　　　　　　　　　　　
藤原 圭志, 森田 真也, 干野 季美子, 福田 篤, 中丸 裕爾, 本間 明宏
Otology Japan, 28, 4, 637, 637, (一社)日本耳科学会, 2018年09月
日本語

当院における嗅神経芽細胞腫の治療方針と成績　　　　　　　　　　　　　　　
中薗 彬, 中丸 裕爾, 鈴木 正宣, 水町 貴諭, 高木 大, 本間 明宏
日本鼻科学会会誌, 57, 3, 429, 429, (一社)日本鼻科学会, 2018年09月
日本語

篩骨動脈を茎とする鼻中隔粘膜弁を用いた鼻中隔穿孔閉鎖術の1例　　　　　　　　　　　　　　　
勝俣 量平, 鈴木 正宣, 中薗 彬, 中丸 裕爾, 本間 明宏
日本鼻科学会会誌, 57, 3, 504, 504, (一社)日本鼻科学会, 2018年09月
日本語

Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer.
Morita S, Mizumachi T, Nakamaru Y, Sakashita T, Kano S, Hoshino K, Fukuda A, Fujiwara K, Homma A
International journal of clinical oncology, 23, 6, 1029, 1037, 2018年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The purpose was to compare survival differences between patients with external auditory canal (EAC) cancer treated according to the University of Pittsburgh modified TNM staging system and those treated in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual on the TNM staging system for cutaneous cancers of the head and neck. METHODS: We performed a retrospective, single-institution review of 60 patients with EAC cancer treated with curative intent between September 2002 and March 2018. Survival outcomes were measured on the basis of the two staging systems. RESULTS: The C-index values for the overall survival (OS) rate revealed that the University of Pittsburgh staging system had higher prognostic accuracy than the 8th edition of the AJCC staging system. Univariable and multivariable analysis showed that T classification according to the University of Pittsburgh staging system was an independent predictor of the OS rate (hazard ratio 5.25; 95% confidence interval 1.38-24.9; P = 0.015). Meanwhile, the AJCC staging system could not differentiate T2 from T3-4 cancers. CONCLUSION: The University of Pittsburgh staging system for patients with EAC cancer is a valuable tool for use in clinical decision-making and predicting survival outcome.

鼻粘膜上皮細胞においてSIRT-1はPolyICに誘導されるMMP9を負に制御する
鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
耳鼻咽喉科免疫アレルギー, 36, 2, 118, 119, 日本耳鼻咽喉科免疫アレルギー学会, 2018年06月
日本語

鼻粘膜上皮細胞においてSIRT-1はPolyICに誘導されるMMP9を負に制御する　　　　　　　　　　　　　　　
鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
耳鼻咽喉科免疫アレルギー, 36, 2, 118, 119, 日本耳鼻咽喉科免疫アレルギー学会, 2018年06月
日本語

Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing
Shinichiro Yasukawa, Satoshi Kano, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Masanobu Suzuki, Takayoshi Suzuki, Akira Nakazono, Shinya Tanaka, Hiroshi Nishihara, Akihiro Homma
International Journal of Clinical Oncology, 23, 5, 1, 9, Springer Tokyo, 2018年05月19日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Background: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. Methods: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. Results: The number of mutant genes increased in the order of IP <
dysplasia <
SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. Conclusion: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.

当科における局所進行外耳道扁平上皮癌の治療成績の検討　　　　　　　　　　　　　　　
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 44, 2, 181, 181, (一社)日本頭頸部癌学会, 2018年05月
日本語

Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up.
Kimura H, Konno S, Makita H, Taniguchi N, Shimizu K, Suzuki M, Kimura H, Goudarzi H, Nakamaru Y, Ono J, Ohta S, Izuhara K, Ito YM, Wenzel SE, Nishimura M, Hi-CARAT investigators
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2018年05月, ［査読有り］, ［国際共著］

当科における局所進行外耳道扁平上皮癌の治療成績の検討　　　　　　　　　　　　　　　
加納 里志, 森田 真也, 中丸 裕爾, 水町 貴諭, 中薗 彬, 福田 篤, 安田 耕一, 鬼丸 力也, 白土 博樹, 本間 明宏
頭頸部癌, 44, 2, 181, 181, (一社)日本頭頸部癌学会, 2018年05月
日本語

Elevated Level of Myeloperoxidase-Deoxyribonucleic Acid Complex in the Middle Ear Fluid Obtained from Patients with Otitis Media Associated with Antineutrophil Cytoplasmic Antibody-associated Vasculitis
Shinya Morita, Yuji Nakamaru, Daigo Nakazawa, Fumihiko Hattanda, Haruki Shida, Yoshihiro Kusunoki, Kanako Watanabe, Sakiko Masuda, Dai Takagi, Masanobu Suzuki, Kimiko Hoshino, Atsushi Fukuda, Utano Tomaru, Akihiro Homma, Akihiro Ishizu
Otology and Neurotology, 39, 4, e257, e262, Lippincott Williams and Wilkins, 2018年04月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective:The purpose was to explore the presence of myeloperoxidase (MPO)-deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil extracellular traps (NETs) in the middle ear fluid, and to clarify the correlation between its quantifiable level and hearing outcome in patients with otitis media associated with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Study Design:Prospective study.Setting:Tertiary referral center.Patients:Nine AAV patients presenting with otitis media.Intervention:Collection of the fluid samples from middle ear.Main Outcome Measure:The quantifiable levels of MPO-DNA complex using an enzyme-linked immunosorbent assay.Results:The quantifiable levels of MPO-DNA complex in patients with AAV were significantly higher than those in controls (p <
0.001). In particular, both ANCA-positive and-negative cases indicated higher levels of MPO-DNA complex compared with the controls (p = 0.004 and p = 0.006, respectively). The significant negative correlations were observed between the level of MPO-DNA complex and the functional hearing values for air (r =-0.82, p = 0.009) and bone conduction (r =-0.73, p = 0.028), respectively.Conclusion:This analysis is the first to reveal the presence of elevated levels of MPO-DNA complex in the middle ear fluid, suggesting the pathogenic role of NETs in otitis media associated with AAV. NETs may be a valuable biomarker for use in clinical decision-making and predicting hearing outcome, regardless of ANCA status.

鼻副鼻腔内反性乳頭腫の悪性転化に関与する遺伝子変異の解析
安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
日本耳鼻咽喉科学会会報, 121, 4, 539, 539, (一社)日本耳鼻咽喉科学会, 2018年04月
日本語

当院における嗅神経芽細胞腫の治療方針と成績
中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
日本耳鼻咽喉科学会会報, 121, 4, 567, 567, (一社)日本耳鼻咽喉科学会, 2018年04月
日本語

ANCA関連血管炎性中耳炎における好中球細胞外トラップの発現
森田 真也, 中丸 裕爾, 干野 季美子, 福田 篤, 本間 明宏
日本耳鼻咽喉科学会会報, 121, 4, 557, 557, (一社)日本耳鼻咽喉科学会, 2018年04月
日本語

当院における嗅神経芽細胞腫の治療方針と成績
中丸 裕爾, 高木 大, 鈴木 正宣, 加納 里志, 水町 貴諭, 中薗 彬, 本間 明宏
日本耳鼻咽喉科学会会報, 121, 4, 567, 567, (一社)日本耳鼻咽喉科学会, 2018年04月
日本語

鼻副鼻腔内反性乳頭腫の悪性転化に関与する遺伝子変異の解析　　　　　　　　　　　　　　　
安川 真一郎, 加納 里志, 畠山 博充, 中丸 裕爾, 高木 大, 水町 貴諭, 鈴木 正宣, 鈴木 崇祥, 中薗 彬, 本間 明宏
日本耳鼻咽喉科学会会報, 121, 4, 539, 539, (一社)日本耳鼻咽喉科学会, 2018年04月
日本語

Clinical Characteristics and Treatment Outcomes for Patients with External Auditory Canal Cholesteatoma
Shinya Morita, Yuji Nakamaru, Atsushi Fukuda, Keishi Fujiwara, Kimiko Hoshino, Akihiro Homma
Otology and Neurotology, 39, 2, 189, 195, Lippincott Williams and Wilkins, 2018年02月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: We aimed to evaluate the clinical features and treatment outcomes for patients with idiopathic and secondary external auditory canal cholesteatoma (EACC), and to validate the treatment strategy from the perspective of hearing as well as etiology and staging. Study Design: Retrospective case series. Setting: Tertiary referral center and affiliated hospitals. Patients: Fifty-eight patients with idiopathic EACC and 14 patients with secondary EACC. Intervention: Conservative management and surgery. Main Outcome Measure: Air conduction (AC) pure-tone averages (PTAs) and mean air-bone gaps (ABGs). Results: There were no significant differences between hearing values before and after conservative management for idiopathic EACC patients with stages I-III, indicating that hearing abilities were preserved. For idiopathic EACC patients with stage IV disease treated with surgery, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 60.3 dB HL to a postoperative value of 32.4 dB HL (p = 0.013), and from 34.3 to 9.5 dB HL (p <
0.001), respectively. For secondary EACC, the AC PTA threshold and mean ABG significantly improved from a preoperative value of 49.5 dB HL to a postoperative value of 23.2 dB HL (p <
0.001), and from 31.4 to 6.7 dB HL (p <
0.001), respectively. Conclusion: The treatment modalities should be selected based on the perspective of hearing as well as the extent of disease and etiology. The early lesions can be treated conservatively, whereas the advanced lesions or cases refractory to conservative management require complete surgical removal of EACC.

Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma.
Konno S, Taniguchi N, Makita H, Nakamaru Y, Shimizu K, Shijubo N, Fuke S, Takeyabu K, Oguri M, Kimura H, Maeda Y, Suzuki M, Nagai K, Ito YM, Wenzel SE, Nishimura M, HiCARAT Investigators
Annals of the American Thoracic Society, 15, 1, 33, 41, American Thoracic Society, 2018年01月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics.Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Results: Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. Conclusions: This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

Relapsing Polychondritis With Increased Bone Marrow Signal on Magnetic Resonance Imaging in a 13-Year-Old Girl.
Kanako Nakayama, Sayaka Yamamoto, Kimiaki Uetake, Masafumi Yamada, Yusuke Tozawa, Masahiro Ueki, Shunichiro Takezaki, Hiroki Nishimura, Yuji Nakamaru, Tomoko Mitsuhashi, Noriko Oyama-Manabe, Keita Sakamoto, Ryuta Arai, Tadashi Ariga
Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 24, 1, 52, 54, 2018年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Value of T1-weighted magnetic resonance imaging in cholesteatoma detection
Atsushi Fukuda, Shinya Morita, Taisuke Harada, Keishi Fujiwara, Kimiko Hoshino, Yuji Nakamaru, Akihiro Homma
Otology and Neurotology, 38, 10, 1440, 1444, Lippincott Williams and Wilkins, 2017年12月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: To reveal the usefulness of T1-weighted (T1W) imaging on diagnostic magnetic resonance (MR) imaging for cholesteatoma. Study Design: A retrospective case review. Setting: Tertiary referral center. Patients: Fifty-three patients (57 ears) suspected to have cholesteatomas and treated (6-82 yr of age). Intervention: Preoperative MR imaging, including non-echo planar (non-EP) diffusion-weighted (DW) and T1W imaging. Main Outcome Measures: Primary outcome measures included the comparison between the diagnostic accuracy for the detection of cholesteatomas using non-EP DW imaging alone (criterion 1) and non-EP DW imaging along with T1W imaging (criterion 2). Diagnostic accuracy was evaluated in each case by comparing MR imaging with surgical findings. Secondary outcome measures included the comparison of the rates of cases showing a high T1W signal between cholesteatomas and noncholesteatomas which showed a high non-EP DW signal. Results: The sensitivity, specificity, and accuracy according to criterion 1 were 93.5, 63.6, and 87.7% and those according to criterion 2 were 89.1, 100, and 91.2%, respectively. Of 43 cholesteatoma cases indicating a high non-EP DW signal, only 2 cases showed a high T1W signal (5%). On the other hand, all four noncholesteatoma cases indicating high non-EP DW signal showed a high T1W signal (100%), and these rates were significantly different ( p<
0.001). Conclusion: Our results suggest that T1W imaging may aid in the exclusion of false-positive cases on diagnostic non-EP DW MR imaging for cholesteatomas. A combination of non- EP DW and T1W imaging may improve the specificity and accuracy compared with non-EP DW imaging alone.

急性感音難聴患者におけるムンプスIgM抗体陽性率の検討(第2報)
福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 赤澤 茂, 中丸 裕爾, 本間 明宏
Otology Japan, 27, 4, 568, 568, (一社)日本耳科学会, 2017年10月
日本語

抗好中球細胞質抗体関連血管炎症候群に伴う難治性中耳炎における好中球細胞外トラップの発現　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 干野 季美子, 福田 篤, 本間 明宏
Otology Japan, 27, 4, 429, 429, (一社)日本耳科学会, 2017年10月
日本語

鼻粘膜上皮細胞での自然免疫シグナルによるMMP9の発現誘導　　　　　　　　　　　　　　　
鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
日本鼻科学会会誌, 56, 3, 429, 429, (一社)日本鼻科学会, 2017年09月
日本語

鼻粘膜上皮細胞での自然免疫シグナルによるMMP9の発現誘導　　　　　　　　　　　　　　　
鈴木 正宣, 中丸 裕爾, 高木 大, 本間 あや, Vreugde Sarah, Wormald Peter-John, 本間 明宏
日本鼻科学会会誌, 56, 3, 429, 429, (一社)日本鼻科学会, 2017年09月
日本語

IgG4関連疾患における鼻副鼻腔病変の検討
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
耳鼻咽喉科免疫アレルギー, 35, 2, 238, 239, 日本耳鼻咽喉科免疫アレルギー学会, 2017年08月
日本語

Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma
Tomohiko Kakizaki, Hiromitsu Hatakeyama, Yuji Nakamaru, Dai Takagi, Takatsugu Mizumachi, Tomohiro Sakashita, Satoshi Kano, Akihiro Homma, Satoshi Fukuda
ONCOLOGY LETTERS, 14, 1, 987, 992, SPANDIDOS PUBL LTD, 2017年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a > 2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.

当科の弛緩部型中耳真珠腫の臨床的検討
福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 中丸 裕爾, 福田 諭
日本耳鼻咽喉科学会会報, 120, 4, 535, 535, (一社)日本耳鼻咽喉科学会, 2017年04月
日本語

IgG4関連疾患における鼻副鼻腔病変の検討
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
日本耳鼻咽喉科学会会報, 120, 4, 557, 557, (一社)日本耳鼻咽喉科学会, 2017年04月
日本語

外耳道癌組織における免疫組織化学的手法に基づく発現分子解析　　　　　　　　　　　　　　　
森田 真也, 本間 明宏, 中丸 裕爾, 安川 真一郎, 福田 篤, 福田 諭
日本耳鼻咽喉科学会会報, 120, 4, 566, 566, (一社)日本耳鼻咽喉科学会, 2017年04月
日本語

Sinus Computed Tomographic Findings in Adult Smokers and Nonsmokers with Asthma. Analysis of Clinical Indices and Biomarkers.
Hirokazu Kimura, Satoshi Konno, Yuji Nakamaru, Hironi Makita, Natsuko Taniguchi, Kaoruko Shimizu, Masaru Suzuki, Junya Ono, Shoichiro Ohta, Kenji Izuhara, Masaharu Nishimura
Annals of the American Thoracic Society, 14, 3, 332, 341, 2017年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: When they occur together, sinusitis and asthma are often thought to represent anatomically separate components of the same chronic inflammatory airway disease. Information about the effect of smoking on the interaction between sinusitis and asthma in patients who have both disorders is limited. OBJECTIVES: To evaluate the effect of cigarette smoking on the relationship between the presence and severity of sinusitis and selected asthma-related indices in adults who have asthma. METHODS: This study included 127 patients with severe asthma and 79 patients with mild to moderate asthma. Clinical data were obtained from all subjects during a 2-day stay at Hokkaido University Hospital (Sapporo, Japan). The Lund-Mackay scoring system was used to assess the anatomic extent and severity of sinusitis as revealed by sinus computed tomographic (CT) images obtained during hospitalization. We examined associations between Lund-Mackay scores and a variety of asthma-related indices and levels of biomarkers in blood and sputum. To clarify the effect of smoking on these associations, we conducted separate analyses for nonsmoking (<10 pack-years; n = 130) and smoking subjects (≥10 pack-years; n = 76). MEASUREMENTS AND MAIN RESULTS: In our cohort of adults with asthma, we found significant positive relationships between the presence and severity of sinusitis as assessed by Lund-Mackay score and the severity of asthma as measured by percent predicted FEV1 or FEV1/FVC for nonsmoking subjects (<10 pack-years) but not for cigarette smokers (>10 pack-years). Lund-Mackay scores correlated with blood and sputum eosinophil counts, serum IgE levels, and fractional exhaled nitric oxide, regardless of smoking status. Lund-Mackay scores also showed significant positive associations with serum periostin and chemokine C-C motif ligand 18 levels, regardless of smoking status, whereas a positive association with plasma osteopontin level was seen only for nonsmoking subjects. CONCLUSIONS: We found an association between the severity of sinusitis on CT imaging and the severity of concomitant asthma on spirometry for nonsmoking adults but not for smokers. In adults with asthma, CT imaging evidence of severe sinusitis indicates intense Th2-related inflammation, regardless of smoking status.

Expression of p53, p16, cyclin D1, epidermal growth factor receptor and Notch1 in patients with temporal bone squamous cell carcinoma
Shinya Morita, Yuji Nakamaru, Akihiro Homma, Shinichiro Yasukawa, Hiromitsu Hatakeyama, Tomohiro Sakashita, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, 1, 181, 189, SPRINGER JAPAN KK, 2017年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Background The aim of this study was to investigate the expression of p53, p16, cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and to evaluate the association between these biomarkers and clinicopathological features.
Methods We performed a retrospective, single-institution review of 30 TBSCC patients treated with curative intent between April 2006 and March 2015. All tissue samples were obtained from pretreatment biopsy specimens or surgical specimens and using IHC staining.
Results Ten patients were categorized as T1, seven as T2, five as T3 and eight as T4. Nine patients had clinically positive lymph node metastasis. The positive expression of p53 and EGFR was significantly associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was significantly more frequent in patients with positive lymph node metastasis compared with patients without node involvement (P = 0.017). In the analysis of the association between protein expression by IHC staining and prognosis, the positive expression of EGFR and Notch1 was significantly correlated with poor survival outcomes in TBSCC (P = 0.015 and P = 0.025)
Conclusion Overexpression of p53 and EGFR may be valuable biomarkers for identifying individuals at high risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR was significantly associated with poor survival outcome. Anti-EGFR therapy has potential for use as the treatment modality of choice for advancedstage TBSCC as well as other head and neck squamous cell carcinomas.

Evaluation of Vestibular Functions in Patients with Vogt-Koyanagi-Harada Disease
Keishi Fujiwara, Shinya Morita, Kimiko Hoshino, Atsushi Fukuda, Yuji Nakamaru, Akihiro Homma
AUDIOLOGY AND NEURO-OTOLOGY, 22, 3, 190, 195, KARGER, 2017年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Vogt-Koyanagi-Harada (VKH) disease is an idiopathic, multi-system autoimmune disorder characterized by bilateral, diffuse granulomatous uveitis associated with neurological, audiovestibular, and dermatological manifestations. The purpose of this study is to investigate vestibular functions in patients with VKH disease. A total of 43 patients with VKH disease in Hokkaido University Hospital were enrolled in this study. Subjective symptoms such as dizziness or vertigo and the results of various vestibular examinations including nystagmus testing, caloric testing, and vestibular-evoked myogenic potential (VEMP) testing were investigated. Eight of 42 patients (19.0%) complained of subjective vestibular symptoms. On the other hand, 12 of 28 patients (42.9%) showed nystagmus, and 7 of 15 patients (46.7%) showed unilateral or bilateral weakness in the caloric test. VEMP testing was performed for 16 patients. Seven (43.8%) and 8 (50.0%) patients were evaluated as abnormal in cervical VEMP and ocular VEMP testing, respectively. The rate of detection of nys-tagmus was significantly higher than that of subjective symptoms. As vestibular dysfunction in patients with VKH disease cannot be detected through history taking alone, nystagmus testing, caloric testing, and VEMP testing should be performed to evaluate vestibular functions associated with VKH disease. It is considered that abnormal VEMP findings are associated with otolith organ dysfunction. (C) 2017 S. Karger AG, Basel

Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery
A. Honma, D. Takagi, Y. Nakamaru, A. Homma, M. Suzuki, S. Fukuda
JOURNAL OF LARYNGOLOGY AND OTOLOGY, 130, 12, 1147, 1152, CAMBRIDGE UNIV PRESS, 2016年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery.
Methods: Blood eosinophil numbers and serum interleukin- 5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed.
Results: Blood eosinophil numbers and serum interleukin- 5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 +/- 26.1 vs 443.9 +/- 76.6 cells/mu l, p < 0.05), and decreased significantly after surgery (825.7 +/- 26.1 vs 76.7 +/- 25.8 cells/mu l, p < 0.05).
Conclusion: Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.

アレルギー性鼻炎モデルマウスにおける鼻粘膜時計遺伝子発現リズム　　　　　　　　　　　　　　　
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
日本鼻科学会会誌, 55, 3, 468, 468, (一社)日本鼻科学会, 2016年09月
日本語

The Outcomes of Surgery and Chemoradiotherapy for Temporal Bone Cancer
Shinya Morita, Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Atsushi Fukuda, Satoshi Fukuda
OTOLOGY & NEUROTOLOGY, 37, 8, 1174, 1182, LIPPINCOTT WILLIAMS & WILKINS, 2016年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: We aimed to evaluate the prognostic factors and efficacy of treatment modalities for patients with temporal bone cancer, and to determine if definitive chemoradiotherapy (CRT) for advanced-stage disease can provide a substitute for highly invasive surgeries.
Study Design: Retrospective case series.
Setting: Tertiary referral center.
Patients: Sixty-six patients with previously untreated squamous cell carcinoma of the temporal bone treated with curative intent between April 1997 and March 2015.
Intervention: Surgery alone, radiotherapy (RT) alone, surgery followed by RT or definitive CRT.
Main Outcome Measure: The overall survival (OS) rate.
Results: The 5-year OS rate for each T classification was 100% for T1, 76.2% for T2, 55.6% for T3, and 36.7% for T4. Univariable and multivariable analysis showed that T classification was an independent predictor of the OS rate (hazard ratio 5.66; 95% confidence interval 1.51-27.0; p = 0.015). Analysis by treatment modality revealed that the 5-year OS rate for patients with T1-2 was 100% for surgery and 81.3% for RT alone. The rate for patients with T3-4 was 52.1% for definitive CRT and 55.6% for surgery followed by RT with or without chemotherapy.
Conclusions: Patients with T1-2 benefited from surgical intervention without significant morbidity or mortality. Our findings also suggested that definitive CRT might be appropriate as the first-line treatment for T3-4, especially in cases with unresectable tumors.

A Retrospective Study of G-Tube Use in Japanese Patients Treated with Concurrent Chemoradiotherapy for Hypopharyngeal Cancer
Akihiro Homma, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Tomohiro Sakashita, Rinnosuke Kuramoto, Yuji Nakamaru, Rikiya Onimaru, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
PLOS ONE, 11, 8, e0161734, PUBLIC LIBRARY SCIENCE, 2016年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective
Late toxicity after concurrent chemoradiotherapy (CCRT), such as dysphagia, in patients with squamous cell carcinoma of the head and neck has received a good deal of attention recently. The gastrostomy tube (G-tube) dependence rate 1 year after CCRT was reported to be 16.7-42.9% in Western countries. We evaluated swallowing outcomes after CCRT in patients with hypopharyngeal cancer (HPC) treated in our hospital and compared them with previous reports.
Methods
We reviewed 96 consecutive patients with a HPC treated by radiotherapy with intravenous or intra-arterial chemotherapy between 2006 and 2013 at Hokkaido University Hospital, Sapporo, Japan.
Results
At 1 month after CCRT, 13 patients (13.7%) used a G-tube, whereas 5/91 (5.5%) and 4/81 (4.9%) used a G-tube at 3 and 6 months, respectively. Two patients used a G-tube at 12 and 24 months after CCRT (G-tube use rate: 2.8% at 12 months, and 3.2% at 24 months). The variables female, posterior wall primary, stage IV, ECOG performance status of 2, and smoking status were significantly associated with G-tube use at 12 months after CCRT, whereas the route of cisplatin administration was not related to G-tube use (p = 0.303).
Conclusions
The G-tube use rate up to 1year could be lower in Japanese patients than in Western patients according to previous reports. In particular, Japanese patients resume oral intake sooner than Western patients. Further study of the incidence of dysphagia after CCRT by ethnicity is required to clarify the differences in dysphagia after CCRT.

Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.
Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, Toshifumi Yamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase
Nature microbiology, 1, 6, 16054, 16054, 2016年04月25日, ［査読有り］, ［国際誌］
英語, Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.

Comparison of hearing outcomes after treatment for early-stage external auditory canal cancer
Shinya Morita, Yuji Nakamaru, Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Masayori Masuya, Satoshi Fukuda
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 38, E1110, E1116, WILEY-BLACKWELL, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. The purpose of this study was to compare the hearing outcomes after surgery with reconstruction of the external auditory canal in combination with tympanoplasty, radiotherapy (RT) alone, and surgery followed by postoperative RT for T1 to 2N0M0 external auditory canal cancer.
Methods. We performed a retrospective, single-institution review of consecutive patients with early-stage external auditory canal cancer treated with surgery and/or RT between April 1997 and August 2013. Audiological data included the pretreatment hearing thresholds and those obtained at 12 months after the completion of therapy.
Results. When we compared the functional gains for air-conduction pure-tone average thresholds and mean air-bone gaps, those in the surgery group (n = 10) were significantly higher than those in the RT (n = 13) and surgery 1 RT (n = 5) groups.
Conclusion. Adequate techniques for reconstruction of the external auditory canal in combination with tympanoplasty after complete surgical resection is useful for hearing preservation in addition to good survival outcomes. (c) 2015 Wiley Periodicals, Inc.

Sonographic findings of immunoglobulin G4-related sclerosing sialadenitis
Satomi Omotehara, Mutsumi Nishida, Megumi Satoh, Mamiko Inoue, Yusuke Kudoh, Tatsunori Horie, Akihiro Homma, Yuji Nakamaru, Kanako C. Hatanaka, Chikara Shimizu
JOURNAL OF MEDICAL ULTRASONICS, 43, 2, 257, 262, SPRINGER JAPAN KK, 2016年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose We evaluated the sonographic findings of immunoglobulin G4-related sclerosing sialadenitis (IgG4-SS).
Methods Nineteen patients with IgG4-SS and 12 healthy volunteers (controls) were enrolled. The following sonographic features were evaluated: (1) enlargement of the submandibular gland by measurement of the longitudinal diameter and thickness; (2) the contour texture of the submandibular gland (smooth or rough); (3) the internal echo texture, categorized into three sonographic patterns (homogeneous, multiple hypoechoic nodule, and diffuse hypoechoic); and (4) quantitative color Doppler signaling.
Results The longitudinal diameter and the thickness (mean +/- A SD) of the submandibular gland were significantly greater in patients than in controls (p = 0.005 and p < 0.001, respectively). Contour roughness was seen in 62.9 and 8.3 % of patients and controls (p < 0.001), respectively. Homogeneous echo textures alone were seen in controls, whereas multiple hypoechoic nodule patterns were seen in 60 % of the patients, and diffuse hypoechoic patterns were seen in 40 %. Color Doppler signaling (mean +/- A SD) was significantly higher in patients as compared with controls (p < 0.001).
Conclusion Patients could be distinguished from healthy volunteers using four distinctive sonographic findings, suggesting that ultrasonography would be a useful diagnostic tool for IgG4-SS.

TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin.
Suzuki M, Watanabe M, Nakamaru Y, Takagi D, Takahashi H, Fukuda S, Hatakeyama S
Cellular and molecular life sciences : CMLS, 73, 5, 1085, 1101, SPRINGER BASEL AG, 2016年03月, ［査読有り］
英語, 研究論文（学術雑誌）, NF kappa B is one of the central regulators of cell survival, immunity, inflammation, carcinogenesis and organogenesis. The activation of NF kappa B is strictly regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. Several types of ubiquitination play important roles in multi-step regulations of the NF kappa B pathway. Some of the tripartite motif-containing (TRIM) proteins functioning as E3 ubiquitin ligases are known to regulate various biological processes such as inflammatory signaling pathways. One of the TRIM family proteins, TRIM39, for which the gene has single nucleotide polymorphisms, has been identified as one of the genetic factors in Behcet's disease. However, the role of TRIM39 in inflammatory signaling had not been fully elucidated. In this study, to elucidate the function of TRIM39 in inflammatory signaling, we performed yeast two-hybrid screening using TRIM39 as a bait and identified Cactin, which has been reported to inhibit NF kappa B- and TLR-mediated transcriptions. We show that TRIM39 stabilizes Cactin protein and that Cactin is upregulated after TNF alpha stimulation. TRIM39 knockdown also causes activation of the NF kappa B signal. These findings suggest that TRIM39 negatively regulates the NF kappa B signal in collaboration with Cactin induced by inflammatory stimulants such as TNF alpha.

Preoperative Assessments for Sinonasal Inverted Papilloma
Nakamaru Yuji, Takagi Dai, Suzuki Masanobu, Homma Aya, Fukuda Satoshi
日本鼻科学会会誌, 55, 1, 114, 114, 日本鼻科学会, 2016年
日本語

Otologic and Rhinologic Manifestations of Eosinophilic Granulomatosis with Polyangiitis
Yuji Nakamaru, Dai Takagi, Masanobu Suzuki, Aya Homma, Shinya Morita, Akihiro Homma, Satoshi Fukuda
AUDIOLOGY AND NEURO-OTOLOGY, 21, 1, 45, 53, KARGER, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease that manifests as asthma, recurrent sinusitis and peripheral eosinophilia. In this study, we investigated the clinical features of the ear and nasal manifestations of EGPA in comparison with those of granulomatosis with polyangiitis (GPA). Materials and Methods: Twenty-one patients diagnosed with EGPA were studied. The frequency of otologic manifestations, the degree of hearing loss and the frequency of nasal symptoms were assessed. The onset of ear symptoms, sinusitis and asthma in patients with EGPA were also examined. Results: Eleven patients (52.4%) with EGPA demonstrated otologic symptoms. The EGPA patients commonly presented mild-to-moderate mixed or sensorineural hearing loss. The pattern of hearing loss was mainly flat, and all but 1 patient achieved complete remission from their hearing impairments. Eighteen patients (85.7%) with EGPA demonstrated nasal symptoms. Patients with EGPA showed a significantly higher incidence of nasal polyps than did those with GPA. The median Lund and Mackey scoring system score was 13.7 for patients with EGPA, and ethmoid sinus shadows were more severe than those of the maxillary sinus. Most ear symptoms associated with EGPA were observed after definitive diagnosis, although sinusitis and asthma tended to manifest themselves before diagnosis. There were significant differences between the onset of ear symptoms and those of asthma and sinusitis. Conclusion: As over 80% of patients with EGPA had nasal symptoms and over half had ear symptoms, otolaryngologists should be aware of this disease. Recognition of the characteristic ear and nasal symptoms are thought to be particularly important to obtain an early diagnosis of EGPA. (C) 2016 S. Karger AG, Basel

The Short- and Long-Term Outcome of Intratympanic Steroid Therapy as a Salvage Treatment for Acute Low-Tone Sensorineural Hearing Loss without Episodes of Vertigo
Shinya Morita, Yuji Nakamaru, Keishi Fujiwara, Keiji Iizuka, Masayori Masuya, Akihiro Homma, Atsushi Fukuda, Satoshi Fukuda
AUDIOLOGY AND NEURO-OTOLOGY, 21, 3, 132, 140, KARGER, 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: To evaluate the hearing outcomes of intratympanic steroid (ITS) treatment for patients with acute low-tone sensorineural hearing loss (ALHL) after failure of initial therapy and to investigate the recurrence and progression to definite Meniere's disease (MD) during a long-term follow-up. Methods: We retrospectively reviewed the medical records of 90 patients with refractory ALHL who were followed up for at least 1 year between January 2000 and April 2014. Patients who responded poorly to initial medical treatment received intratympanic dexamethasone injections (ITS group) or isosorbide administration for 4 weeks (diuretic group) as salvage treatment options according to their choice of management. The control group did not receive ITS or the diuretic, due to their refusal of both medical treatments. The hearing outcomes were evaluated 1 month, 1 year and 5 years after the completion of the second-line therapy, and the rates of recurrence and progression to MD were measured during a follow-up period of at least 1 year. Results: Twenty-seven patients in the ITS group, 39 patients in the diuretic group and 24 patients in the control group were enrolled. Of these, 12 patients in the ITS group, 15 patients in the diuretic group and 12 patients in the control group were followed up for over 5 years. We found that the recovery rates and the audiometric functional values after 1 month and 1 year in the ITS group were significantly higher than those in the diuretic and control groups. However, there were no significant differences in the recovery rates or the audiometric functional values after 5 years, or in the rates of recurrence and progression to MD between the groups. Conclusions: Salvage ITS therapy can provide a relatively good short-term hearing outcome for ALHL patients who have persistent hearing loss despite conventional treatment. However, both recurrence and progression to MD after treatment were observed in some patients during the long-term follow-up. (C) 2016 S. Karger AG, Basel

Distinct phenotypes of cigarette smokers identified by cluster analysis of patients with severe asthma
Satoshi Konno, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, Masaharu Nishimura
Annals of the American Thoracic Society, 12, 12, 1771, 1780, American Thoracic Society, 2015年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital staywere used for cluster analysis. After clustering using clinical variables, the sputum levels of 14moleculeswere measured to biologically characterize the clinical clusters. Measurements and Main Results: Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. Conclusions: This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.
Konno S, Taniguchi N, Makita H, Nakamaru Y, Shimizu K, Shijubo N, Fuke S, Takeyabu K, Oguri M, Kimura H, Maeda Y, Suzuki M, Nagai K, Ito YM, Wenzel SE, Nishimura M, Hi-CARAT Investigators
Annals of the American Thoracic Society, 12, 12, 1771, 1780, 2015年12月, ［査読有り］

Glucocorticoids Reset the Nasal Circadian Clock in Mice
Aya Honma, Yoshiko Yamada, Yuji Nakamaru, Satoshi Fukuda, Ken-ichi Honma, Sato Honma
ENDOCRINOLOGY, 156, 11, 4302, 4311, ENDOCRINE SOC, 2015年11月, ［査読有り］
英語, 研究論文（学術雑誌）, The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans.

Early and long-term morbidity after minimally invasive total laryngo-pharyngo-esophagectomy with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision
Akihiro Homma, Yuji Nakamaru, Hiromitsu Hatakeyama, Takatsugu Mizumachi, Satoshi Kano, Jun Furusawa, Tomohiro Sakashita, Toshiaki Shichinohe, Yuma Ebihara, Satoshi Hirano, Hiroshi Furukawa, Toshihiko Hayashi, Yuhei Yamamoto, Satoshi Fukuda
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, 272, 11, 3551, 3556, SPRINGER, 2015年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Total laryngo-pharyngo-esophagectomy (TLPE) with gastric pull-up reconstruction is still considered to be associated with major complications and a significant risk of in-hospital death. Minimally invasive esophagectomy, avoiding thoracotomy and laparotomy, has been increasingly performed for esophageal malignancies with the hope of reducing mortality and morbidity, such as pulmonary complications. The aim in this study was to assess early and long-term morbidity as well as treatment outcomes in patients treated with TLPE with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. From 2004 to 2013, 10 patients with a median age of 64 years (range 47-71 years) underwent minimally invasive TPLE with gastric pull-up reconstruction. Seven of the 10 patients had previously received radiotherapy. As for early postoperative complications, no patient died during the early postoperative period, and pneumonia was observed in 1, skin necrosis in 1, pseudomembranous enterocolitis in 1, arrhythmia in 2, hemorrhage in the neck in 2, anastomotic leakage in the neck in 3, and tracheal necrosis in 6 patients. Three patients developed tracheostomal stenosis as a long-term postoperative complication, and an anastomotic stricture was observed in one patient. All patients were able to achieve oral intake, but 3 patients required feeding tube support. In conclusion, postoperative systemic complications during the early postoperative period were considered to be acceptable, although wound complications such as tracheal necrosis and anastomotic leakage were commonly observed. Therefore, this minimally invasive procedure might help reduce mortality and morbidity in patients requiring TLPE with gastric pull-up reconstruction.

Management for squamous cell carcinoma of the nasal cavity and ethmoid sinus: A single institution experience
Akihiro Homma, Yuji Nakamaru, Tomohiro Sakashita, Rikiya Onimaru, Shunsuke Terasaka, Kazuhiko Tsuchiya, Daisuke Yoshida, Koichi Yasuda, Hiromitsu Hatakeyama, Jun Furusawa, Takatsugu Mizumachi, Satoshi Kano, Hiroki Shirato, Satoshi Fukuda
AURIS NASUS LARYNX, 42, 5, 377, 381, ELSEVIER SCI LTD, 2015年10月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Here we report our experience of patients with squamous cell carcinoma (SCC) of the nasal cavity and ethmoid sinus (NC&ES) together with an analysis of treatment outcomes.
Methods: A retrospective analysis was performed using data from 25 consecutive patients treated between 2000 and 2012. Four patients were diagnosed with T1, 3 with T2, 4 with T3, 7 with T4a, and 7 with T4b disease. No patient had lymph node metastasis.
Results: Twelve patients were treated with surgery with/without radiotherapy and with/without chemotherapy. Of these, 4 underwent endoscopic surgery without an open approach and 3 required an anterior skull base approach. Thirteen were treated with radiotherapy; 1 with radiotherapy alone, and 4 and 8 with intravenous and intra-arterial chemotherapy, respectively. The 5-yr overall survival for T1-3, T4a, and T4b disease was 53.9%, 71.4%, and 29.0%, respectively. The 5-yr disease-specific survival for T1-3, T4a, and T4b disease was 74.1%, 71.4%, and 29.0%, respectively.
Conclusion: Our treatment policy for patients with SCC of NC&ES, which basically follows the NCCN guideline, was considered to be appropriate. However, several points in terms of surgery and nonsurgical approach remain to be solved through further research. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of facial synkinesis at 6 and 12 months after the onset of peripheral facial nerve palsy
Keishi Fujiwara, Yasushi Furuta, Yuji Nakamaru, Satoshi Fukuda
AURIS NASUS LARYNX, 42, 4, 271, 274, ELSEVIER SCI LTD, 2015年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To investigate the time course of synkinesis as a sequela of facial nerve palsy so that we are able to determine an appropriate time for deciding the outcome of recovery in patients with facial nerve palsy.
Methods: Nineteen consecutive patients with peripheral facial nerve palsy who developed synkinesis were enrolled. We compared the degree of synkinesis at 6 and 12 months after the onset of palsy. Our investigation consisted of (1) scoring using the Sunnybrook facial grading system and (2) computing the asymmetry (%) in eye opening width. We also judged whether all 19 cases were cured or not based on the treatment outcome criteria of the Japan Society of Facial Nerve Research at 6 and 12 months.
Results: The synkinesis score based on Sunnybrook facial grading system and the degree of asymmetry in eye opening width during mouth movement deteriorated significantly between the 6th and 12th month after the onset of palsy. One of the cases regarded as "cured" at the 6th month was later judged to be "non-cured" due to deterioration in the synkinesis score at the 12th month.
Conclusion: From our results, synkinesis deteriorated after the 6th month from the onset of palsy. Therefore, we should follow up the degree of synkinesis until at least the 12th month, and the outcome of recovery in patients with facial synkinesis should be evaluated at least 12 months after the onset. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Oxidative Stress Regulates IL-4 Gene Expression in Mast Cells through the Reduction of Histone Deacetylase
Yuji Nakamaru, Dai Takagi, Akihiro Homma, Shigetsugu Hatakeyama, Satoshi Fukuda
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 152, 1, 48, 52, SAGE PUBLICATIONS LTD, 2015年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective Many proinflammatory cytokines are regulated by the acetylation and deacetylation of the core histone. Since dysregulation of T helper 2 cytokine production is a key in the pathogenesis of allergic diseases, we examined the role of histone deacetylase (HDAC) on interleukin (IL)-4 gene expression in mast cells. We also examined whether oxidative stress has any impact on HDAC activity.
Study Design In vitro study.
Setting Academic research laboratory.
Methods An IgE-sensitized mast cell line (RBL-2H3 cells) was treated with varying concentrations of the HDAC inhibitors trichostatin A (TSA) and H2O2 and stimulated with antigens. The amount of IL-4 gene expression was quantified by real-time polymerase chain reaction. Quantitative measurement of IL-4 in the cell supernatant was performed using enzyme-linked immunosorbent assay. Moreover, HDAC activity was measured with the use of a nonisotopic assay that utilized an HDAC Fluorescent Activity Assay Kit.
Results IL-4 mRNA expression was induced by antigens in IgE-sensitized RBL-2H3 cells. Pretreatment with TSA and H2O2 enhanced IL-4 mRNA expression up to 5-fold in a dose-dependent manner. Furthermore, HDAC activity in RBL-2H3 cells was reduced after treatment with H2O2.
Conclusion Our results suggest that oxidative stress may up-regulate IL-4 gene expression in mast cells via a decrease in HDAC activity.

The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck
Akihiro Homma, Tomohiro Sakashita, Hiromitsu Hatakeyama, Satoshi Kano, Takatsugu Mizumachi, Yuji Nakamaru, Daisuke Yoshida, Rikiya Onimaru, Kazuhiko Tsuchiya, Koichi Yasuda, Hiroki Shirato, Satoshi Fukuda
ACTA OTO-LARYNGOLOGICA, 135, 9, 950, 954, TAYLOR & FRANCIS LTD, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, Conclusions: Superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) is considered to be one of the treatments of choice for patients with adenoid cystic carcinoma (ACC) who prefer not to undergo radical surgery. Objective: To evaluate the efficacy of RADPLAT for patients with ACC of the head and neck. Patients and methods: Between 2001-2010, nine patients with untreated ACC were given superselective intra-arterial infusion of cisplatin (100-120 mg/m(2)/ week) with simultaneous intravenous infusion of thiosulfate to neutralize cisplatin toxicity and radiotherapy (65-70 Gy). Results: Five patients had tumors arising in the base of the tongue, two in the maxillary sinus, and the remaining two in the nasopharynx. The median follow-up period was 9 years 7 months (9; 7) (range = 4; 6-12; 5), and the 5-year local control (LC), overall survival (OS), and disease-free survival rates were 88.9%, 88.9%, and 55.6%, respectively. The 10-year OS rate was 57.1%, but all patients who remained alive for over 10 years are still alive with disease. Primary tumor recurrence was observed in five of the nine patients, with the median time to recurrence being 6 years (range = 4-9 years). Five of the nine patients had distant metastasis, and of these three patients also had primary recurrence.

Prediction of the Attachment Site of Sinonasal Inverted Papillomas by Preoperative Imaging
Yuji Nakamaru, Noriyuki Fujima, Dai Takagi, Akiko Tsukahara, Daisuke Yoshida, Satoshi Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 123, 7, 468, 474, SAGE PUBLICATIONS INC, 2014年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Accurate preoperative identification of the attachment site is the key to the successful surgical management of sinonasal inverted papillomas (IPs). This study investigated the value of preoperative imaging to identify the attachment sites of IPs.
Methods: We analyzed 10 consecutive patients with pathologically proven IPs. Two radiologists predicted the attachment sites of IPs from computed tomography (CT), 3.0 Tesla magnetic resonance imaging (3.0T MRI), 1.5T MRI, and CT plus 3.0T MRI. The actual tumor attachment sites were confirmed via pathological examination of specimens and compared with the predicted sites.
Results: Computed tomography showed the highest sensitivity (P < .0001), although both MRI formats showed greater specificity (P < .0001). The sensitivity of MRI plus CT was equal to that of CT and better than that of MRI (P <.0001), whereas its specificity was better than that of CT (P < .0001) and comparable to that of MRI. Prediction using 3.0T MRI appeared slightly superior to that using 1.5T MRI in terms of sensitivity and specificity, although the differences were not significant.
Conclusion: Computed tomography and MRI had different features for prediction of sinonasal IP attachment sites. Preoperative CT plus MRI provided more useful information than CT or MRI alone.

Otologic Manifestations of Immunoglobulin G4-Related Disease
Dai Takagi, Yuji Nakamaru, Satoshi Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 123, 6, 420, 424, SAGE PUBLICATIONS INC, 2014年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: Immunoglobulin (Ig) G4-related disease is systemic, and it has been reported that patients with IgG4-related disease complain of symptoms involving numerous organs. However, there are few reports concerning the otologic manifestations of IgG4-related disease. The purpose of this study is to investigate the clinical features of the otologic manifestations in IgG4-related disease.
Methods: We recruited 39 consecutive patients diagnosed with IgG4-related disease. Otologic symptoms, laboratory data, and audiogram findings were retrospectively examined. Mucosal tissues from the inferior turbinate were obtained from subjects before treatment. The serum IgG4 and eosinophil levels together with clinical features were analyzed.
Results: Five of the 39 cases had some otologic symptoms. Otitis media with effusion was present in 2 patients. Sensorineural hearing loss was also present in 1 patient. Eosinophilic otitis media was present in 2 patients with bilateral rhinosinusitis and bronchial asthma, and elevated serum eosinophil levels. Oral prednisolone was effective in the treatment of IgG4-related disease.
Conclusion: We revealed a new clinical entity associated with the otologic manifestations of IgG4-related disease.

早期外耳道癌症例に対する治療前後の聴力に関する検討
森田 真也, 中丸 裕爾, 本間 明宏, 坂下 智博, 桝谷 将偉, 福田 諭
日本耳鼻咽喉科学会会報, 117, 4, 565, 565, (一社)日本耳鼻咽喉科学会, 2014年04月
日本語

Characteristics and Prognosis of Hearing Loss Associated with Vogt-Koyanagi-Harada Disease
Shinya Morita, Yuji Nakamaru, Nobuyuki Obara, Masayori Masuya, Satoshi Fukuda
AUDIOLOGY AND NEURO-OTOLOGY, 19, 1, 49, 56, KARGER, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To clarify the characteristics and prognosis of hearing loss associated with Vogt-Koyanagi-Harada (VKH) disease. Methods: We retrospectively examined 85 patients diagnosed with VKH disease between January 1996 and December 2012. The control group included age-and gender-matched individuals without definitive ear disease. The patients with VKH disease were treated with high-dose systemic corticosteroids, which were tapered off gradually over a period of 6 months or more by the treating ophthalmologists according to the severity of the ocular inflammation. The features of hearing loss were analyzed based on pure tone audiometric data obtained at the initial presentation according to diagnostic criteria based on the ISO 7029 standard. The efficacy of corticosteroid therapy was evaluated by audiometry at the initial presentation and during therapy for 3-6 months. Results: In patients with VKH disease, the rate of hearing loss detected by audiometry was significantly higher than that of either subjective hearing loss (p < 0.001) or tinnitus (p < 0.001). Bilateral symmetrical hearing loss was the most common type of auditory disturbance associated with VKH disease. The degree of hearing loss was generally low, with no patients showing profound hearing loss. Hearing thresholds were significantly elevated at high frequencies compared with those at low-to-mid frequencies (p < 0.001). Hearing thresholds at all frequencies after high-dose corticosteroid therapy were significantly better than those at initial presentation (p < 0.001), and the rate of patients who returned to within normal-range pure tone thresholds at all frequencies was 74.8%. Conclusions: As auditory manifestations cannot be detected through history taking alone, audiometry should be performed to evaluate hearing loss associated with VKH disease. Early administration of high-dose systemic corticosteroids is effective for treating the auditory manifestations, which generally show a relatively good short-term prognosis. (C) 2013 S. Karger AG, Basel

Hearing Preservation after Lateral Temporal Bone Resection for Early-Stage External Auditory Canal Carcinoma
Shinya Morita, Yuji Nakamaru, Akihiro Homma, Tomohiro Sakashita, Masayori Masuya, Satoshi Fukuda
AUDIOLOGY AND NEURO-OTOLOGY, 19, 6, 351, 357, KARGER, 2014年, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To evaluate postoperative hearing outcomes after lateral temporal bone resection (LTBR) with reconstruction of the external auditory canal (EAC) and conductive function for early-stage EAC carcinoma. Methods: We retrospectively examined patients diagnosed with early-stage EAC carcinoma treated with surgery alone between January 2006 and December 2012. Patients who had postoperative adjuvant chemotherapy and/or radiotherapy were excluded. Patients receiving LTBR in combination with tympanoplasty were divided into two groups based on the reconstruction of the EAC with and without (w/o) split-thickness skin grafts (STSGs). Audiological data included the preoperative hearing thresholds and the most recent postoperative hearing thresholds obtained at least 12 months after surgery. The hearing outcome was evaluated based on puretone audiograms using the Committee on Hearing and Equilibrium guidelines of the American Academy of Otolaryngology-Head and Neck Surgery for the evaluation of the results of treatment of conductive hearing loss. The postoperative quality of life (QOL) for patients was evaluated using the Glasgow Benefit Inventory (GBI). Results: All patients (n = 15) achieved disease-free survival without significant morbidity or mortality. When we compared the mean air-bone gaps after surgery, those in the STSG group (n = 8) were found to be significantly lower than those in the w/o STSG group (n = 7; p < 0.001). The success rate for postoperative hearing was 75.0% in the STSG group, which was significantly higher than that in the w/o STSG group (p = 0.014). All patients in the w/o STSG group showed stenosis and closure of the EAC at fewer than 10 months after surgery. In contrast, all patients in the STSG group showed preserved conformation of the new EAC for more than 12 months after surgery. When we compared the mean GBI score between the two groups of patients, the overall and general health scores in the STSG group were found to be significantly higher than those in the w/o STSG group (p = 0.021, p = 0.001). Conclusions: Reconstruction of the EAC using a rolled-up STSG technique in combination with tympanoplasty after LTBR is useful for hearing preservation and the observation of locoregional lesions after surgery, resulting in improved QOL for patients. (C) 2014 S. Karger AG, Basel

耳鳴に対するエスシタロプラムの有効性に関する検討　　　　　　　　　　　　　　　
桝谷 将偉, 中丸 裕爾, 森田 真也, 福田 諭
Otology Japan, 23, 4, 774, 774, (一社)日本耳科学会, 2013年10月
日本語

外側側頭骨切除術に一期的鼓室形成術を施行した早期外耳道癌症例の検討　　　　　　　　　　　　　　　
中丸 裕爾, 森田 真也, 桝谷 将偉, 福田 諭
Otology Japan, 23, 4, 669, 669, (一社)日本耳科学会, 2013年10月
日本語

Vogt-小柳-原田病における聴力像の特徴および聴力予後の検討　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 小原 修幸, 桝谷 将偉, 福田 諭
Otology Japan, 23, 4, 513, 513, (一社)日本耳科学会, 2013年10月
日本語

IgG4関連硬化性疾患に併発した副鼻腔炎
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭
耳鼻咽喉科免疫アレルギー, 31, 2, 73, 74, 日本耳鼻咽喉科免疫アレルギー学会, 2013年06月
日本語

Nasal manifestations of immunoglobulin G4-related disease
Masanobu Suzuki, Yuji Nakamaru, Shigeru Akazawa, Takatsugu Mizumachi, Masanori Maeda, Dai Takagi, Kanako C. Hatanaka, Satoshi Fukuda
LARYNGOSCOPE, 123, 4, 829, 834, WILEY-BLACKWELL, 2013年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives/Hypothesis: Immunoglobulin (Ig)G4-related disease is a systemic syndrome, characterized by sclerosing lesions that mainly affect the exocrine tissue. Although some patients with IgG4-related disease complain of nasal symptoms, there are few reports concerning the nasal manifestations of this disease. We investigated the clinical and pathological features of the nasal manifestations of IgG4-related disease. Study Design: Retrospective review in a tertiary referral hospital. Methods: Twenty-three consecutive patients with IgG4-related disease, six allergic rhinitis (AR) patients, and eight healthy subjects (HS) were evaluated. Nasal symptoms, local findings of the nasal cavity, and laboratory data were examined. Mucosal tissues from the inferior turbinate were obtained from all subjects before treatment. The level of IgG4-positive plasma cells and other infiltrating cells, and the number of nasal glands in the nasal subjects were compared among the three groups. Results: Ten (43.4%) of 23 cases had some nasal symptoms, such as nasal obstruction and nasal crusting. Thirteen cases (56.5%) had numerous IgG4-positive plasma cell infiltration in the nasal mucosa. IgG4-positive plasma cells, CD3, and CD4 were significantly higher in the IgG4-related disease group than in the HS and AR groups, whereas the number of nasal glands in the IgG4-related disease group was significantly lower than in the HS and AR groups. Conclusions: The inflammatory lesions associated with IgG4-related disease exist on the nasal membrane. Thus, the nasal manifestations of IgG4-related disease were thought to be different from AR.

Dysregulation of Histone Deacetylase and Histone Acetyltransferase in Development of Wegener's Granulomatosis
Dai Takagi, Yuji Nakamaru, Masanobu Suzuki, Satoshi Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 121, 12, 816, 820, ANNALS PUBL CO, 2012年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: We investigated the function of the decreases in histone deacetylase (HDAC) and histone acetyltransferase (HAT) in Wegener's granulomatosis (WG) patients compared with healthy subjects.
Methods: Seven patients with WG, diagnosed according to the American College of Rheumatology criteria, were examined. Fresh peripheral blood mononuclear cells were isolated from the WG patients and healthy subjects, and then whole-cell proteins were prepared. We measured the total HDAC and HAT activity in peripheral blood mononuclear cells from WG patients. The HDAC2 expression was analyzed by Western blot.
Results: We found that total HDAC activity was significantly decreased in WG patients compared to that in healthy subjects (p < 0.05). Furthermore, we found a negative correlation between total HDAC activity and C-reactive protein titer. Total HAT activity was significantly increased in WG patients.
Conclusions: These results demonstrated reduced HDAC activity and an increase in HAT activity in WG. These were associated with concomitant induction of WG-related inflammation. Thus, dysregulation of HDAC and HAT may contribute to the disease pathogenesis of WG.

急性副鼻腔炎に対するLevofloxacin 1日1回500mg投与の治療効果
高木 大, 中丸 裕爾, 鈴木 正宣, 福田 諭
耳鼻咽喉科・頭頸部外科, 84, 13, 1021, 1026, (株)医学書院, 2012年12月
日本語, 急性副鼻腔炎に対するLevofloxacin 500mg1日1回投与の早期治療効果と安全性を検討した。解析対象は26症例で、急性炎症を起こしてから10日以内であり、投与期間は全て7日間であった。重症度は中等症6例、重症20例であった。投与開始3日後、自覚症状、他覚所見ともに有意なスコアの改善を認め、投与終了時の有効率は84.6%であり、特に重症例での有効率は90.0%であった。やや有効にとどまった症例を4例認めたが、自覚症状、他覚所見どちらも改善を示さない無効例はなかった。やや有効の4例中2例は、鼻中隔彎曲等による中鼻道の狭小化があり、その後内視鏡的副鼻腔手術を施行して改善した。24例には細菌学的検査を施行し、10例から12種の原因菌が同定された。Haemophilus influenzaeが5株と最多で、Streptococcus pneumoniaeの4株が続いた。副作用は1例に軽度の全身そう痒感が発現したが、内服は継続可能であった。

Extranodal natural killer/T-cell lymphoma: a diagnostic dilemma
Hiroko Yanagi, Yuji Nakamaru, Dai Takagi, Kanako Kubota, Satoshi Fukuda
RHINOLOGY, 50, 3, 325, 331, INT RHINOLOGIC SOC, 2012年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The diagnosis of extranodal natural killer (NK)/T-cell lymphoma (NK/T-cell lymphoma) is often difficult and any delay in its diagnosis leads to a worsened prognosis. We analysed the factors that make the diagnosis of this type of tumour difficult.
Methodology/Principal: We retrospectively reviewed the medical records of 20 patients with NK/T-cell lymphoma treated in our department, and assessed the clinical features and laboratory findings of the cases. Moreover, we classified factors related to delays in diagnosing NK/T cell lymphoma as follows: (1) insufficient specimen size, (2) massive necrosis, (3) large number of inflammatory cells, and (4) poor atypia. We selected cases requiring two or more biopsies for correct diagnosis and checked which factors were the main cause of misdiagnosis.
Results: The average period required for a correct diagnosis was 12.8 months. The most frequent factor leading to diagnostic delay was inflammatory cell infiltration. Massive necrosis and poor atypia were also important factors in diagnostic delay.
Conclusions: In cases with necrotic lesions of the nose or pharynx, the possibility of NK/T cell lymphoma should be explored and samples, of as large a size as possible, should be obtained together with EBER-ISH for pathological examination. Repeat biopsies should also be performed for diagnosis.

早期外耳道癌に対して外側側頭骨切除術に一期的鼓室形成術を施行した4症例　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 福田 諭
Otology Japan, 22, 4, 579, 579, (一社)日本耳科学会, 2012年09月
日本語

ヒストン脱アセチル化作用を有するSIRT1によるMMP-9の発現調節
中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
耳鼻咽喉科免疫アレルギー, 30, 2, 215, 216, 日本耳鼻咽喉科免疫アレルギー学会, 2012年06月
日本語

ヒストンアセチル化がWegener肉芽腫症におよぼす影響について
高木 大, 中丸 裕爾, 鈴木 正宣, 福田 諭
耳鼻咽喉科免疫アレルギー, 30, 2, 76, 77, 日本耳鼻咽喉科免疫アレルギー学会, 2012年06月
日本語

IgG4関連疾患の鼻腔病変における組織学的検討
鈴木 正宣, 中丸 裕爾, 赤澤 茂, 水町 貴諭, 前田 昌紀, 高木 大, 福田 諭
耳鼻咽喉科免疫アレルギー, 30, 2, 70, 71, 日本耳鼻咽喉科免疫アレルギー学会, 2012年06月
日本語

IgG4関連疾患の鼻腔病変における組織学的検討
鈴木 正宣, 中丸 裕爾, 赤澤 茂, 水町 貴諭, 前田 昌紀, 高木 大, 福田 諭
日本耳鼻咽喉科学会会報, 115, 4, 413, 413, (一社)日本耳鼻咽喉科学会, 2012年04月
日本語

Otolaryngologic Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Yuji Nakamaru, Dai Takagi, Nobuhiko Oridate, Akihiro Homma, Satoshi Fukuda
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 146, 1, 119, 121, SAGE PUBLICATIONS LTD, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is characterized by systemic necrotizing vasculitis, and patients fall into 2 groups: those with proteinase 3-ANCA and those with myeloperoxidase-ANCA. As infections are a trigger of ANCA-associated vasculitis, this disease tends to localize in areas around the upper airway. In this study, the authors compared ear and nasal symptoms between patients with proteinase 3-ANCA and those with myeloperoxidase-ANCA. We undertook a retrospective case series study of 34 patients diagnosed with ANCA-associated vasculitis. The otologic symptoms were divided into 3 types: chronic otitis media, secretory otitis media, and sensorineural hearing loss. Chronic otitis media was more common in patients with proteinase 3-ANCA (P=.001), whereas secretory otitis media was more frequently found in patients with myeloperoxidase-ANCA (P=.007). Crust formation (P=.001), saddle nose (P=.024), and sinusitis (P=.001) were more common in patients with proteinase 3-ANCA than in those with myeloperoxidase-ANCA. Marked differences were observed in the disease spectrum between the 2 ANCA groups.

Giant frontal mucocele occurring 32 years after frontal bone fracture: A case report
Yuuta Kamoshima, Shunsuke Terasaka, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda, Kiyohiro Houkin
Case Reports in Neurology, 4, 1, 34, 37, 1, 2012年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Giant mucoceles of the frontal sinus are rare but their recognition is important in the differential diagnosis of proptosis and fronto-orbital lesions. The authors describe a patient with frontal giant mucocele with intracranial as well as orbit and ethmoid sinus involvement. Thirty-two years after a frontal sinus fracture, a 51-year-old female presented with headache, and left exophthalmos and ophthalmoplegia. Computed tomography and magnetic resonance imaging demonstrated a giant frontal sinus mucocele with extension into the left anterior cranial fossa. The mucocele was treated with a transcranial and endoscopic transnasal approach. The frontal sinus was then cranialized with reconstruction of the posterior wall, and finally a wide nasal drainage was performed. The clinical symptoms disappeared immediately after surgery. Copyright © 2012 S. Karger AG, Basel.

Modified Lothrop Procedureにより内視鏡的に切除した前頭洞内に茎を持つ内反性乳頭腫症例　　　　　　　　　　　　　　　
中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭
日本鼻科学会会誌, 50, 3, 379, 379, (一社)日本鼻科学会, 2011年11月
日本語

Transoral surgery of the larynx and pharynx using Weerda-type videolaryngoscope　　　　　　　　　　　　　　　
Nobuhiko Oridate, Akihiro Homma, Yuji Nakamaru, Seigo Suzuki, Satoshi Fukuda
Oto-Rhino-Laryngology Tokyo, 54, 5, 355, 359, 2011年10月15日
日本語, 研究論文（学術雑誌）, We introduced our experiences of transoral surgery of the larynx and pharynx, such as resection of early stage hypopharyngeal carcinoma or epiglitoc cysts and removal of foreign body, using Weerda-type videolaryngoscope along with telescope and Hi-vison CCD camera system in Hokkaido University Hospital.

IgG4関連疾患における鼻腔病変の検討　　　　　　　　　　　　　　　
赤澤 茂, 中丸 裕爾, 高木 大, 水町 貴諭, 福田 諭
耳鼻咽喉科免疫アレルギー, 29, 2, 77, 78, 日本耳鼻咽喉科免疫アレルギー学会, 2011年06月
日本語

Preservation of the nasolacrimal duct during endoscopic medial maxillectomy for sinonasal inverted papilloma
Yuji Nakamaru, Yasushi Furuta, Dai Takagi, Nobuhiko Oridate, Satoshi Fukuda
RHINOLOGY, 48, 4, 452, 456, INT RHINOLOGIC SOC, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP).
Methodologies: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumours arising from the anterior part of the maxilla, sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer's test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery.
Results: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumours. No patient suffered tumour recurrence. There was no difference in lacrimal duct function between the diseased and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100.
Conclusions: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.

Preservation of the nasolacrimal duct during endoscopic medial maxillectomy for sinonasal inverted papilloma
Yuji Nakamaru, Yasushi Furuta, Dai Takagi, Nobuhiko Oridate, Satoshi Fukuda
RHINOLOGY, 48, 4, 452, 456, INT RHINOLOGIC SOC, 2010年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: To assess the efficacy of a new endonasal medial maxillectomy technique (EMM) for the treatment of inverted papilloma (IP).
Methodologies: A prospective series of 55 consecutive patients diagnosed with IP between March 2002 and April 2009 were entered into this study. The new surgical technique was applied to tumours arising from the anterior part of the maxilla, sinus. After conventional EMM, the entire nasolacrimal duct was separated from the bony component of the nasolacrimal canal and preserved. Schirmer's test and a visual analog scale (VAS) score were used to assess the lacrimal duct function after surgery.
Results: Ten of the 55 patients underwent the new surgical procedure. All patients were categorized with stage T3 or T4 tumours. No patient suffered tumour recurrence. There was no difference in lacrimal duct function between the diseased and healthy side of the nasolacrimal duct. The mean VAS score was 2.8/100.
Conclusions: This new surgical technique preserves the whole length of the nasolacrimal unit. It also offers several advantages including good visualization, nasolacrimal function after surgery and fewer adverse effects such as facial numbness and epiphora.

Frontal trephination for frontal sinus mucocele　　　　　　　　　　　　　　　
Yuji Nakamaru, Satoshi Iizuka, Dai Takagi, Satoshi Fukuda
Oto-Rhino-Laryngology Tokyo, 53, 5, 49, 50, 2010年10月
日本語, 研究論文（学術雑誌）, A surgery for the frontal sinus mucocele is one of the most difficult operations among endoscopic sinus surgery (ESS), because of the high incidence of the recurrence. The Frontal trephination is originally developed to point out nasofrontal duct during ESS. We used the frontal trephination to treat the frontal sinus mucocele. The instrument enabled to clean up nasofrontal duct after surgery and to keep patency of the duct.

反復性鼻出血に対する内視鏡下蝶口蓋動脈結紮術施行例の検討
古田 康, 松村 道哉, 鈴木 正宣, 中丸 裕爾
日本鼻科学会会誌, 49, 3, 415, 415, (一社)日本鼻科学会, 2010年07月
日本語

Sublingual immunotherapy with house dust extract for house dust-mite allergic rhinitis in children
Syuji Yonekura, Yoshitaka Okamoto, Daiju Sakurai, Shigetoshi Horiguchi, Toyoyuki Hanazawa, Atsuko Nakano, Fumiyo Kudou, Yuji Nakamaru, Kohei Honda, Akira Hoshioka, Naoki Shimojo, Yoichi Kohno
Allergology International, 59, 4, 381, 388, Japanese Society of Allergology, 2010年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: House dust extract is used in conventional immunotherapy for house dust-mite (HDM) allergic rhinitis in Japan. However, an alternative administration route is desired. The aims of the present double blind, placebo-controlled trial were to evaluate the therapeutic efficacy and safety of sublingual immunotherapy (SLIT) with house dust extract in pediatric patients with HDM allergic rhinitis. Methods: The study population comprised 31 subjects (21 males and 10 females) aged from 7 to 15 years old. Twenty patients (the active group) received house dust extract and 11 received placebo via sublingual administration. Extract or placebo (1 ml) was administered at 10-fold dilution once weekly for 40 weeks. During the study period, the subjects recorded their daily nasal symptoms and use (dose and frequency) of other medications in a nasal allergy diary. Results: The symptom scores in the active group began to decrease about 24 weeks after initiation of treatment and significant differences between the active and placebo groups were observed after 30 weeks. The average scores for the last four weeks of the study were significantly lower than those for the first four weeks in the active group but not in the placebo group. The only local adverse effect was a bitter taste reported by one patient. There were no other local or systemic adverse effects associated with SLIT. Conclusions: Our results suggest that SLIT with house dust extract for more than 30 weeks is safe and effective treatment for HDM allergic rhinitis in children.© Japanese Society of Allergology.

反復性鼻出血に対する内視鏡下蝶口蓋動脈結紮術施行例の検討
鈴木 正宣, 大谷 文雄, 松村 道哉, 蠣崎 文彦, 森田 真也, 佐藤 宏紀, 中丸 裕爾, 古田 康
耳鼻咽喉科・頭頸部外科, 82, 1, 67, 72, (株)医学書院, 2010年01月
日本語, 反復性鼻出血に対し内視鏡下蝶口蓋動脈結紮術を施行した14例15側(男11例・女3例・42〜76歳)について報告した。適応は、保存的療法で止血できず、蝶口蓋動脈の支配領域からの出血が疑われる症例とした。鼻出血の危険因子として、高血圧合併8例、5例に抗凝固薬使用を認めた。術前全例にガーゼタンポンがなされ、うち9例はバルーンタンポンも施行した。術前の輸血は2例に要した。手術時間は平均80分で、粘膜下下甲介切除術を7例に、鼻中隔矯正術を4例に併施した。出血量はほとんどが少量であったが、4例では100〜400mlと多かった。術後のガーゼ留置期間は平均1.6日間で、ガーゼ抜去時の出血が3例でみられたが、動脈性ではなくガーゼで止血できた。血小板機能異常を合併した1例のみ術後も出血が続き、バイポーラー焼灼術、アルゴンプラズマレーザーによる鼻腔粘膜焼灼術を要した。手術から退院までの平均日数は4.9日で、重篤な合併症はなかった。

Endoscopic transseptal approach for sinonasal inverted papilloma attached to the anterior maxillary siuns　　　　　　　　　　　　　　　
Yuji Nakamaru, Tosihiro Hara, Takatsugu Mizumachi, Fukuda Satosi, Furuta Yasushi
Oto-Rhino-Laryngology Tokyo, 52, 5, 386, 388, 2009年10月
日本語, 研究論文（学術雑誌）, Sinonasal inverted papillomas (IP) are the one of the most common benign neoplasm of the nasal and paranasal sinus lesions. Transnasal endoscopic medial maxillectomy (EMM) for this tumor was developed and IP could be managed by endonasal approach. However the IP attached to the anterior wall of the maxially sinus could not be managed with EMM. We present new technique make a small hall in the nasal septum and use instruments from opposite side of nasal cavity. We resected 4 case of IP patients and completely control of the tumor without complication. This approach provided better visualization and wide working space of the instruments.

A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9
Yuji Nakamaru, Chaitanya Vuppusetty, Hiroo Wada, Jill C. Milne, Misako Ito, Christos Rossios, Mark Elliot, James Hogg, Sergei Kharitonov, Hajime Goto, Jean E. Bemis, Peter Elliott, Peter J. Barnes, Kazuhiro Ito
FASEB JOURNAL, 23, 9, 2810, 2819, FEDERATION AMER SOC EXP BIOL, 2009年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Inappropriate elevation of matrix metalloproteinase-9 (MMP9) is reported to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The object of this study was to identify the molecular mechanism underlying this increase of MMP9 expression, and here we show that oxidative stress-dependent reduction of a protein deacetylase, SIRT1, known as a putative antiaging enzyme, causes elevation of MMP9 expression. A sirtuin inhibitor, splitomycin, and SIRT1 knockdown by RNA interference led an increase in MMP9 expression in human monocytic U937 cells and in primary sputum macrophages, which was detected by RT-PCR, Western blot, activity assay, and zymography. In fact, the SIRT1 level was significantly decreased in peripheral lungs of patients with COPD, and this increase was inversely correlated with MMP9 expression and MMP9 promoter activation detected by a chromatin immunoprecipitation assay. H(2)O(2) reduced SIRT1 expression and activity in U937 cells; furthermore, cigarette smoke exposure also caused reduction of SIRT1 expression in lung tissue of A/J mice, with concomitant elevation of MMP9. Intranasal treatment of a selective and novel SIRT1 small molecule activator, SRT2172, blocked the increase of MMP9 expression in the lung as well as pulmonary neutrophilia and the reduction in exercise tolerance. Thus, SIRT1 is a negative regulator of MMP9 expression, and SIRT1 activation is implicated as a novel therapeutic approach to treating chronic inflammatory diseases, in which MMP9 is abundant.-Nakamaru, Y., Vuppusetty, C., Wada, H., Milne, J. C., Ito, M., Rossios, C., Elliot, M., Hogg, J., Kharitonov, S., Goto, H., Bemis, J. E., Elliott, P., Barnes, P. J., Ito, K. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9. FASEB J. 23, 2810-2819 (2009). www.fasebj.org

術中に内反性乳頭腫と判明した一側性上顎洞病変症例　　　　　　　　　　　　　　　
水町 貴諭, 中丸 裕爾, 高木 大, 福田 諭
日本鼻科学会会誌, 48, 3, 276, 276, (一社)日本鼻科学会, 2009年08月
日本語

鼻腔病変を有したIgG4関連疾患2症例　　　　　　　　　　　　　　　
水町 貴諭, 中丸 裕爾, 前田 昌紀, 高木 大, 久保田 佳奈子, 河上 洋, 福田 諭
アレルギーの臨床, 29, 8, 712, 716, (株)北隆館, 2009年08月
日本語, 鼻腔に病変を呈したIgG4関連疾患の2症例を経験した。症例はいずれも50歳代の男性で、鼻腔に痂皮の付着を認めた。血清IgG4値は高値で、下鼻甲介からの生検では腺組織に異型はなく、間質にIgG4陽性の形質細胞の浸潤を認めた。IgG4関連の病変は1例は自己免疫性膵炎をはじめ全身の臓器にみられたが、他の1例は頭頸部領域に限局していた。病変が全身にみられた症例に対してはステロイドの全身治療を、頭頸部に限局していた症例に対してはステロイド点鼻療法を行ったが、いずれも病変は軽快し、現在のところ再燃はなく経過観察中である。(著者抄録)

Voice-Related Quality of Life After Treatment of Laryngeal Cancer
Nobuhiko Oridate, Akihiro Homma, Seigo Suzuki, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Tomohiro Sakashita, Noriko Nishizawa, Yasushi Furuta, Satoshi Fukuda
ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY, 135, 4, 363, 368, AMER MEDICAL ASSOC, 2009年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To determine patient-perceived voice-related quality of life in patients treated with various methods based on the results of Voice-Related Quality of Life (VRQOL) and Voice Handicap Index-10 (VHI-10) questionnaires.
Design: The VRQOL and VHI-10 questionnaires.
Setting: University hospital.
Patients: One hundred thirty-seven patients who had received definitive treatment of laryngeal cancer were followed-up at Hokkaido University Hospital, Sapporo, Japan, and were alive with no evidence of malignancy at the time of the survey.
Main Outcome Measure: Patient-perceived voice-related quality of life based on the results of the VRQOL and VHI-10 questionnaires.
Results: The mean VRQOL scores for patients who had undergone radiotherapy (n=63), chemoradiotherapy (n=29), laser surgery (n=14), or total laryngectomy (n=27) as final treatment of laryngeal cancer were 92.6, 92.9, 85.5, and 68.4, respectively; the mean VHI-10 scores were 2.87, 2.34, 5.43, and 11.26, respectively.
Conclusion: The VRQOL and VHI-10 questionnaires are important in judging the overall effectiveness of treatment options for laryngeal cancer.

Complications of Skull Base Surgery: An Analysis of 30 Cases
Tomohiro Sakashita, Nobuhiko Oridate, Akihiro Homma, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Yutaka Sawamura, Yuhei Yamamoto, Yasushi Furuta, Satoshi Fukuda
SKULL BASE-AN INTERDISCIPLINARY APPROACH, 19, 2, 127, 132, THIEME MEDICAL PUBL INC, 2009年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors. Design: Retrospective analysis. Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases). Main outcome measures: Perioperative complications and risk factor associated with their incidence. Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported. Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.

Complications of Skull Base Surgery: An Analysis of 30 Cases
Tomohiro Sakashita, Nobuhiko Oridate, Akihiro Homma, Yuji Nakamaru, Fumiyuki Suzuki, Hiromitsu Hatakeyama, Shigenari Taki, Yutaka Sawamura, Yuhei Yamamoto, Yasushi Furuta, Satoshi Fukuda
SKULL BASE-AN INTERDISCIPLINARY APPROACH, 19, 2, 127, 132, THIEME MEDICAL PUBL INC, 2009年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: To evaluate the risk factors for perioperative complications among patients undergoing craniofacial resection for the treatment of skull base tumors. Design: Retrospective analysis. Participants: The study group comprised 29 patients with skull base tumors (22 malignant and 7 benign) who underwent 30 craniofacial resections at Hokkaido University Hospital between 1989 and 2006. Of these cases, 21 had undergone prior treatment by radiation (16 cases), surgery (7 cases), or chemotherapy (1 case). Moreover, 19 needed extended resection involving the dura (11 cases), brain (5 cases), orbit (12 cases), hard palate (5 cases), skin (3 cases), or cavernous sinus (2 cases). Main outcome measures: Perioperative complications and risk factor associated with their incidence. Results: Perioperative complications occurred in 12 patients (40%; 13 cases). There was a significant difference between complication rates for cases with and without prior therapy (52.4% vs. 11.1%). The complication rate for dural resection cases was 81.8%. There was a significant difference between complication rates for cases with and without dura resection. No postoperative mortality was reported. Conclusions: Craniofacial resection is a safe and effective treatment for skull base tumors. However, additional care is required in patients with extended resection (especially dural) and those who have undergone prior therapy.

マイクロデブリッダーが有用であった成人型多発性喉頭乳頭腫の1症例
鈴木 正宣, 折舘 伸彦, 本間 明宏, 中丸 裕爾, 畠山 博充, 目須田 康, 古田 康, 福田 諭
耳鼻咽喉科・頭頸部外科, 81, 3, 219, 221, (株)医学書院, 2009年03月
日本語, 42歳男。4ヵ月前に嗄声が出現し、保存的治療でいったん改善したが、再増悪を来たした。間接喉頭鏡で左披裂部内側壁、左声帯に3ヶ所、右声帯に2ヶ所の喉頭腫瘍を認め、喉頭ファイバースコピーで腫瘍は乳頭状増殖を示した。喉頭乳頭腫の診断で喉頭直達鏡による腫瘍切除術を施行し、一部採取した腫瘍の迅速病理では悪性所見なしの結果であった。喉頭用スキマーブレード(2.9mm)を装着したマイクロデブリッダーを用いて腫瘍切除を行い、腫瘍自体は軟らかく、ブレード内に吸引された腫瘍のみを切除可能であった。回転数はブレードの熱による瘢痕化を防ぐため、毎分60回転の超低速とした。ごく少量の出血を認めたが、マイクロデブリッダーによる吸引と20万倍エピネフリン塗布で対処できた。切除組織の病理組織像は核異型、分裂像に乏しく、乳頭腫と診断された。術後は沈黙療法を行い、4日目に退院した。嗄声は改善し、術後5ヵ月で再増悪、腫瘍再発はない。

内視鏡下鼻副鼻腔内反性乳頭腫手術における上顎洞前壁の処理 対側鼻腔からのアプローチ法　　　　　　　　　　　　　　　
中丸 裕爾, 古田 康, 原 敏浩, 水町 貴諭, 福田 諭
日本鼻科学会会誌, 47, 3, 290, 290, (一社)日本鼻科学会, 2008年08月
日本語

IgG4関連疾患としての鼻腔病変について　　　　　　　　　　　　　　　
水町 貴諭, 前田 昌紀, 中丸 裕爾, 福田 諭
日本鼻科学会会誌, 47, 3, 276, 276, (一社)日本鼻科学会, 2008年08月
日本語

Surgical equipments for endoscopic medial maxillectomy　　　　　　　　　　　　　　　
Yasushi Furuta, Masahiko Saheki, Yuji Nakamaru, Jun Furusawa, Satoshi Fukuda
Oto-Rhino-Laryngology Tokyo, 50, 5, 379, 381, 2007年10月
日本語, 研究論文（学術雑誌）, Advances in endoscopic surgical techniques and technology have led to a less invasive endoscopic approach to the surgery of benign tumors arising from the nasal cavity and paranasal sinuses. In particular, endoscopic surgery has been applied to tumors involving the maxillary sinus by the introduction of an endoscopic medial maxillectomy (EMM). We described our EMM procedure using various surgical equipments for the surgery of sinonasal papilloma. A powered microdebrider was used to debulk tumors and the attachment of the tumor was identified and removed with the normal adjacent mucosa. Intraoperative hemorrhage was managed by the use of an electrocoagulater or a diamond burr. If the tumor extended around the nasolacrimal duct or the anterior wall of the maxillary sinus, the whole medial wall of the maxillary sinus including the nasolacrimal duct was removed and a silicon tube was placed in the duct. In all surgical procedures, the bone underlying the tumor attachments was removed, curetted, or drilled by a diamond burr. We also used an intraoperative image-guided system to assist in excising tumors.

Preoperative staging and surgical approaches for sinonasal inverted papilloma
Keita Oikawa, Yasushi Furuta, Yuji Nakamaru, Nobuhiko Oridate, Satoshi Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 116, 9, 674, 680, ANNALS PUBL CO, 2007年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives: We sought to determine the value of preoperative staging by magnetic resonance imaging (MRI) assessment in the surgical management of sinonasal inverted papillomas (IPs).
Methods: Preoperative MRI staging was used to assess 22 patients with IPs. In addition to the Krouse staging system, T3 cases were categorized as subgroup T3-B if tumors extended into the frontal sinus or the supraorbital recess; otherwise, they were categorized as T3-A. Standard endoscopic sinus surgery (ESS) was the first choice for T1 and T2 cases. Endoscopic approaches, including ESS combined with endoscope-assisted transantral approach and endoscopic medial maxillectomy, were considered in T3-A cases, and external approaches were considered in T3-B cases. Patients were followed for a minimum of 1 year after surgery.
Results: Preoperative MRI staging and postoperative staging were coincident in 21 of the 22 patients (95%). All 8 T2 cases were treated by an endoscopic approach. Of 10 T3-A cases, 9 (90%) were treated by an endoscopic approach and 1 (residual case) was treated by an external approach. All 3 of the T3-B cases underwent an external approach. One T4 case with malignant transformation underwent an external approach followed by radiotherapy. After a median follow-up period of 22 months, none of the 22 patients had had a recurrence. No major complications were observed after endoscopic approaches, but epiphora or hemorrhage requiring transfusion occurred in 3 of the 5 patients (60%) who underwent external approaches.
Conclusions: Preoperative staging of IP by MRI is useful for selecting cases that can be managed by endoscopic approaches, resulting in lower rates of tumor recurrence and morbidity.

喉頭癌治療後の音声に関するQOLの検討　　　　　　　　　　　　　　　
折舘 伸彦, 古田 康, 本間 明宏, 鈴木 清護, 中丸 裕爾, 鈴木 章之, 畠山 博充, 瀧 重成, 坂下 智博, 西澤 典子, 目須田 康, 福田 諭
頭頸部癌, 33, 2, 178, 178, (一社)日本頭頸部癌学会, 2007年05月
日本語

IL-21 enhances dendritic cell ability to induce interferon-gamma production by natural killer T cells
Masanori Maeda, Yoshiki Yanagawa, Kazuya Iwabuchi, Keita Minami, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda, Kazunori Onoe
IMMUNOBIOLOGY, 212, 7, 537, 547, ELSEVIER GMBH, URBAN & FISCHER VERLAG, 2007年, ［査読有り］
英語, 研究論文（学術雑誌）, Interleukin (IL)-21 shows pleiotropic effects on the proliferation, differentiation, and effector functions of leukocytes. However, the influence of IL-21 on dendritic cell (DC) activation of natural killer T (NKT) cells has not yet been elucidated. In the present study, we examined the effect of IL-21 on murine myeloid DC ability to induce NKT cell production of interferon-gamma (IFN-gamma) and IL-4. Pretreatment of DCs with IL-21 and a-galactosylceramide (alpha-GalCer), an NKT cell-specific ligand, resulted in the enhanced ability of the DCs to induce NKT cell production of IFN-gamma but not IL-4 in vitro compared to DCs pretreated with alpha-GalCer alone. A similar effect of IL-21 was observed when DCs pretreated with IL-21 and alpha-GalCer in vitro were transferred into naive mice. Direct administration of IL-21 to the mice also enhanced IFN-gamma production after injection of a-GalCer. Thus, IL-21 can modify DC ability to selectively enhance NKT cell production of IFN-gamma upon stimulation with alpha-GalCer. (c) 2007 Elsevier GmbH. All rights reserved.

Natural killer T cells ameliorate antibody-induced arthritis in macrophage migration inhibitory factor transgenic mice
Dai Takagi, Kazuya Iwabuchi, Masanori Maeda, Yuji Nakamaru, Yasushi Furuta, Satoshi Fukuda, Luc Van Kaer, Jun Nishihira, Kazunori Onoe
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 18, 5, 829, 836, PROFESSOR D A SPANDIDOS, 2006年11月, ［査読有り］
英語, 研究論文（学術雑誌）, Macrophage migration inhibitory factor (MIF) plays an important role in inflammatory diseases. It has been reported that anti-MIF treatment and mif-gene disruption ameliorate joint inflammation in a mouse model of arthritis induced by anti-type II collagen monoclonal antibodies and lipopolysaccharide (anti-IIC mAb/LPS). In the present study, using the anti-HC mAb/LPS system, we have analyzed arthritis in MIF-transgenic (MIFTg) and wild-type C57BL/6 (WT) mice. We found that MIFTg mice developed more severe arthritis than WT mice. The histopathological scores were significantly higher in MIFTg mice and significantly increased numbers of CD69(+) T cells were detected in the spleens of these arthritic MIFTg mice, compared with WT mice. Natural killer T (NKT) cells from MIFTg mice, compared with WT mice, produced reduced amounts of IL-4 upon stimulation with alpha-galactosylceramide (alpha-GalCer). Further, repeated administration of alpha-GalCer to MIFTg mice resulted in a profound reduction of both clinical and histopathological scores of arthritis, with a significant decrease in IL-6. The present findings demonstrate that overexpression of MIF exacerbates inflammation in this arthritis model and that NKT cells play :an ameliorating role upon stimulation with alpha-GalCer in the inflammatory process in MIFTg mice.

IL-21による樹状細胞の機能制御
前田 昌紀, 柳川 芳毅, 岩淵 和也, 中丸 裕爾, 高木 大, 福田 諭, 小野江 和則
耳鼻咽喉科免疫アレルギー, 24, 2, 207, 208, 日本耳鼻咽喉科免疫アレルギー学会, 2006年09月
日本語

咽喉頭酸逆流症状に対する酸抑制治療の効果とHelicobacter pylori感染との関連
折舘 伸彦, 目須田 康, 西澤 典子, 森 美果, 中丸 裕爾, 本間 明宏, 古田 康, 福田 諭
日本気管食道科学会会報, 57, 3, 262, 267, (NPO)日本気管食道科学会, 2006年06月
日本語, 本邦では逆流性食道炎罹患率とHelicobactor pylori感染率について逆相関を示唆する報告が多いが,咽喉頭異常感,慢性咳嗽,嗄声などの咽喉頭酸逆流症状を訴える患者におけるH.pylori感染率についての報告はまだない.われわれは咽喉頭酸逆流症状にて北海道大学病院耳鼻咽喉科を受診した患者のうち血清H.pylori抗体を測定し得た67例を対象としてH.pylori抗体陽性率,咽喉頭酸逆流症状,酸抑制治療への反応性との関連を検討した.対象患者群の血清抗H.pylori抗体の陽性率は61.2%であり,H.pylori抗体陽性群と陰性群の間には,患者背景,治療前の自覚症状の各項目において有意差を認めなかった.Kaplan-Meier解析により咽喉頭症状改善率についてはH.pylori抗体陽性群は陰性群に比べ酸抑制治療に対する反応が良好であるが,食道症状については両群間に有意差を認めないことが示された(著者抄録)

鼻副鼻腔乳頭腫T3症例に対する内視鏡下手術の検討　　　　　　　　　　　　　　　
及川 敬太, 古田 康, 中丸 裕爾, 本間 明宏, 折舘 伸彦, 福田 諭
日本耳鼻咽喉科学会会報, 109, 4, 410, 410, (一社)日本耳鼻咽喉科学会, 2006年04月
日本語

鼻副鼻腔内反性乳頭腫の術式選択におけるstaging systemの問題点
古田 康, 及川 敬太, 中丸 裕爾, 本間 明宏, 折舘 伸彦, 福田 諭
頭頸部外科, 15, 3, 195, 201, (NPO)日本頭頸部外科学会, 2006年02月
日本語, 著者らは術前MRIにより伸展範囲を評価して術式を選択している.そこで,この方法により治療を行った20例の術式選択についてまとめた.またKrouseのstaging systemの問題点について考察した.男性13例,女性7例を対象にした結果,T1は再発例の1例,T2と診断された8例中6例で,内視鏡下副鼻腔手術(ESS)を施行した.T3と診断された10例中5例は,lateral rhinotomyアプローチによるmedial maxillectomyを選択した.T4と診断されたのは,22年前に初回手術を行った後の再発例の1例だけであった.術後5ヵ月から40ヵ月の経過観察をし,T1からT3症例においては再発は認められていない.T4症例は,放射線照射により縮小したが,照射後7ヵ月が経過し腫瘍が増大しつつある

A prospective study of pollen dispersal prediction and identifying the usefulness of different parameters
Masanori Maeda, Shiro Maguchi, Yuji Nakamaru, Dai Takagi, Satoshi Fukuda
Journal of Otolaryngology of Japan, 109, 5, 455, 460, Oto-Rhino-Laryngological Society of Japan Inc., 2006年, ［査読有り］
日本語, 研究論文（学術雑誌）, BACKGROUND: Birch pollen is the major pollen allergen in Hokkaido, Northern Japan. We reported a Betula masting model based on the resource budget model hypothesis. In addition to weather conditions, cumulative hours of sunlight and mean temperature from May to July of the previous year, this model used the amount of annual pollen dispersed in previous and penultimate years as a parameter based on data from 1990 to 2000. OBJECTIVE: We compared the predicted and observed amount of pollen dispersed for 3 years from 2001 to 2003 and evaluated the usefulness of each parameter in this model. METHODS: Birch pollen was measured using the Durham sampler at the Hokkaido University Graduate School of Medicine Research Institute in Sapporo. RESULTS: The difference between predicted and observed amounts of pollen dispersal was about 200-500 grains cm-2. The annual pollen dispersed in the previous year was found to be the most useful parameter. CONCLUSION: This model is useful in predicting whether the amount of birch pollen will be less than average, about average, more than average, or much more than average.

S100A2 expression as a predictive marker for late cervical metastasis in stage I and II invasive squamous cell carcinoma of the oral cavity
F Suzuki, N Oridate, A Homma, Y Nakamaru, T Nagahashi, K Yagi, S Yamaguchi, Y Furuta, S Fukuda
ONCOLOGY REPORTS, 14, 6, 1493, 1498, PROFESSOR D A SPANDIDOS, 2005年12月, ［査読有り］
英語, 研究論文（学術雑誌）, The purpose of this study was to discover whether S100A2 expression is associated with late cervical metastasis in patients with stage I and II invasive squamous cell carcinoma of the oral cavity. We retrospectively investigated the clinicopathological parameters and S100A2 expression in surgical specimens taken from 52 patients with T1-2N0M0 invasive squamous cell carcinoma of the oral cavity (OSCC) who had not undergone elective neck dissection or irradiation to the neck. All of the clinic opathological factors and S100A2 expression were compared in terms of late cervical metastasis. In univariate analysis, late cervical metastasis correlated with poor overall survival. A higher rate of late cervical metastasis was observed in patients with S100A2-negative tumors than those with S100A2-positive tumors. Multivariate analysis on late cervical metastasis revealed that S100A2 expression was demonstrated to be the only independent factor for late cervical metastasis. Our results indicate that patients with stage I or 11 invasive OSCC without SIOOA2 expression should be considered a high-risk group for late cervical metastasis when a wait-and-see policy for the neck is being considered.

Laryngeal zoster mimicking a laryngeal cancer
E Higuchi, Y Nakamaru, R Ohwatari, T Sakashita, Y Mesuda, A Homma, Y Furuta, S Fukuda
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 133, 4, 647, 647, MOSBY, INC, 2005年10月, ［査読有り］
英語, 研究論文（学術雑誌）

Plantago lanceolata (English plantain) pollinosis in Japan
Y Nakamaru, S Maguchi, N Oridate, D Takagi, Y Furuta, S Fukuda
AURIS NASUS LARYNX, 32, 3, 251, 256, ELSEVIER SCI LTD, 2005年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: The objective was to ascertain the prevalence of Plantago lanceolata (English plantain) pollinosis in Japan.
Methods: A total of 160 patients with allergic rhinitis were examined at the Hokkaido University Hospital Otolaryngology Clinic between January 2002 and December 2003. We investigated the frequency of P. lanceolata antigen-specific immunoglobulin E (IgE) antibody-positive serum using the radioallergosorbent test (RAST), the P. lanceolata pollen counts in the Sapporo area and the clinical symptoms of patients with allergic rhinitis caused by this pollen.
Results: P. lanceolata pollen was dispersed throughout the Sapporo area from mid-May to early September, peaking in the latter half of May. The airborne pollen count showed little variation between years. The P lanceolata RAST-positive rate was 12.8%, which was close to those for ragweed and sagebrush. All subjects showed overlapping antigen sensitization, that is, none displayed sensitization (by RAST) exclusively to P. lanceolata. The onset of subjective symptoms peaked in June and the symptoms worsened from April to October.
Conclusion: P. lanceolata was dispersed over a long period, from mid-May to early September. The P. lanceolata RAST-positive rate (12.8%) was similar to those for sagebrush and ragweed, which are dispersed during the fall. These results suggest that P lanceolata is an important causative agent of pollinosis in Japan. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Macrophage migration inhibitory factor (MIF) contributes to the development of allergic rhinitis
Y Nakamaru, N Oridate, J Nishihira, D Takagi, Y Furuta, S Fukuda
CYTOKINE, 31, 2, 103, 108, ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD, 2005年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine whose expression has been found to be critical to the generation of antigen-specific immune responses. Recent studies suggested that MIF played a role in the initiation and maintenance of allergic diseases. To elucidate MIF's role in the pathogenesis of allergic rhinitis (AR), we sensitized MIF-deficient gene knockout (KO) mice and wild-type (WT) mice intraperitoneally with ovalbumin (OVA) and compared their clinical symptoms and allergic responses after intranasal challenge. Antigen-induced nasal symptoms were significantly reduced in MIF KO mice compared to WT mice. Histological examination of nasal mucosa showed that the number of infiltrating eosinophils in MIF KO mice was significantly lower than that in WT mice (P < 0.05). The concentration of TNF-alpha. in nasal mucosa was also significantly lower in MIF KO mice than in WT mice (P < 0.05). We have demonstrated that the absence of MIF affects several aspects of experimental AR. One mechanism by which these effects might be mediated is by down regulating TNF-alpha. The block of allergic inflammation in MIF KO mice suggests that MIF may play a role in the allergic response. (c) 2005 Elsevier Ltd. All rights reserved.

鼻副鼻腔内反性乳頭腫におけるstage別治療成績の検討　　　　　　　　　　　　　　　
及川 敬太, 古田 康, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
日本耳鼻咽喉科学会会報, 108, 4, 457, 457, (一社)日本耳鼻咽喉科学会, 2005年04月
日本語

頭蓋底再建手術を要した前頭洞嚢胞の一例
藤原 圭志, 古田 康, 中丸 裕爾, 相澤 寛志, 澤村 豊, 福田 諭
頭頸部外科 = Journal of Japan Society for Head and Neck Surgery, 14, 3, 247, 251, (NPO)日本頭頸部外科学会, 2005年02月05日
日本語, 63歳男.左内眼角部の腫脹を指摘された.頭部CTで前頭洞内に充満する軟部組織陰影と前頭洞後壁の骨の菲薄化を認め,MRI所見と併せて前頭洞嚢胞と診断した.内視鏡下両鼻内前頭洞開放術および鼻中隔矯正術を施行し術後経過良好であったが,退院後より頭痛,膿性鼻漏が出現した.前頭洞後壁に肉芽の存在を確認し,画像所見より硬膜炎を合併した急性前頭洞炎と診断した.鼻漏の細菌培養でMRSAを認め,抗生剤投与や鼻洗浄などの保存的治療で頭痛は改善したが,鼻漏は持続した.肉芽除去が必要であったが,鼻内からは困難と考え,開頭による除去術を選択し,前頭開頭による肉芽のデブリードメンおよびgaleo-pericranial flap(GF)による前頭蓋底再建術を施行した.術後経過は良好で,細菌培養でMRSAは認められず,6ヵ月後に施行した頭部MRIガドリニウム造影ではGFで前頭洞内が充填され,硬膜炎が消退している像を認めた.1年9ヵ月経過し,炎症の再燃はない

Prognostic significance of cytoplasmic macrophage migration inhibitory factor expression in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy
F Suzuki, Y Nakamaru, N Oridate, A Homma, T Nagahashi, S Yamaguchi, J Nishihira, Y Furuta, S Fukuda
ONCOLOGY REPORTS, 13, 1, 59, 64, PROFESSOR D A SPANDIDOS, 2005年01月, ［査読有り］
英語, 研究論文（学術雑誌）, The macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine as well as a tumor growth regulator. Although the positive and negative effects of the MIF on tumor cell growth have been reported, the exact role of the MIF in tumorigenesis remains ambiguous. We examined the expression of the MIF protein in tumor specimens obtained from 50 head and neck squamous cell carcinoma (HNSCC) patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m(2)), 4-7 times every week; a total radiation therapy dose of 65-75 Gy over 6.5-7.5 weeks, and determined whether the MIF level is related to clinical outcomes of these patients. Immunostaining with an MIF specific antibody was performed in formalin-fixed, paraffin-embedded specimens. The MIF protein was expressed to various extent in the tumor tissue specimens from the HNSCC patients. Prognostic analysis using the Kaplan-Meier method with regard to the MIF expression revealed that the patients with the MIF-negative tumors had a worse prognosis when compared to those with the MIF expression. The results of this study suggest that the intratumoral MIF expression has a prognostic value in HNSCC patients administered concurrent chemoradiotherapy.

366 SIRT1によるMMP-9発現の調節(サイトカイン, ケモカインとその受容体(2), 第55回日本アレルギー学会秋季学術大会)
中丸 裕爾, 福田 諭, 伊藤 一洋, バーンズピーター
アレルギー, 54, 8, 1098, 1098, 一般社団法人 日本アレルギー学会, 2005年
日本語

鼻咽腔血管線維腫に対するナビゲーションガイド下鼻内内視鏡による摘出の経験
本間 明宏, 中丸 裕爾, 佐伯 昌彦, 福田 諭
頭頸部外科, 14, 2, 109, 113, (NPO)日本頭頸部外科学会, 2004年10月
日本語, 25歳男.右鼻閉が出現し,時々鼻出血があった.ファイバースコープで上咽頭右側に表面平滑,毛細血管の豊富な拍動する腫瘤を認めた.CTでも上咽頭右側から鼻腔後方に造影CTで強く増強される陰影を認めた.MRIではT1強調画像で筋肉と同等の信号,T2強調画像で脳実質と同等の信号を呈していた.診断は上咽頭血管線維腫で,腫瘤が小さいため鼻内内視鏡下に摘出し,術前には塞栓術を行った.手術時にはナビゲーションを用い,出血量が少なく解剖学的位置を正確に確認し摘出できた

Immunoregulatory defects of V alpha 24(+)V beta 11(+) NKT cells in development of Wegener's granulomatosis and relapsing polychondritis
D Takagi, K Iwabuchi, C Iwabuchi, Y Nakamaru, S Maguchi, R Ohwatari, Y Furuta, S Fukuda, S Joyce, K Onoe
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 136, 3, 591, 600, BLACKWELL PUBLISHING LTD, 2004年06月, ［査読有り］
英語, 研究論文（学術雑誌）, The frequency of either CD4(-)8(-) (double negative; DN) or CD4(+) Valpha24(+)Vbeta11(+) NKT cells, the expression of CD1d and the binding of CD1d-tetramer loaded with alpha-galactosylceramide (alpha-GalCer) to NKT cells were analysed in peripheral blood mononuclear cells (PBMCs) of patients with Wegener's granulomatosis (WG), relapsing polychondritis (RP) and healthy subjects (HS). DN and CD4(+) Valpha24(+)Vbeta11(+) NKT cells as well as CD1d-alpha-GalCer tetramer-positive NKT cells, were significantly decreased in number in both WG and RP patients compared to those from HS. When cytokine profiles were analysed in these PBMCs upon stimulation with phorbol ester and calcium ionophore, CD4(+) T cells from patients with WG and RP exhibited a Th1 bias, whereas CD4(+) NKT cells from WG patients in remission showed a Th2 bias. These findings suggest that NKT cells (especially CD4(+) NKT cells) play a regulatory role in Th1 autoimmunity in patients with WG and RP. The reduction in NKT cell counts appears to be associated with the low responsiveness to alpha-GalCer. The dysfunction of NKT cells to recognize ligands such as alpha-GalCer may also contribute to the defects observed in NKT cells from WG and RP patients.

Clinical features of bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody
D Takagi, Y Nakamaru, S Maguchi, Y Furuta, S Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 113, 5, 388, 393, ANNALS PUBL CO, 2004年05月, ［査読有り］
英語, 研究論文（学術雑誌）, In this study, we analyzed the clinical features, diagnostic criteria, treatment, and outcome of atypical bilateral progressive hearing loss associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). The evaluation was made by audiogram and laboratory data in 6 cases treated at Hokkaido University Hospital. We measured MPO-ANCA by enzyme-linked immunosorbent assay; the result was positive in all cases. The hearing loss developed bilaterally and progressed to total deafness within several weeks. The onset of hearing loss was not simultaneous in the 2 ears. Methylprednisolone pulse therapy was effective in 9 ears. Three ears showed no improvement; 2 of the 3 ears had already exhibited total deafness at the first visit. After the treatment, the titer of MPO-ANCA decreased in all patients. The level of MPO-ANCA should be tested in patients with bilateral progressive hearing loss of unknown origin and can be used as a marker of the disease's activity.

鼻副鼻腔乳頭腫の術式選択におけるstaging systemの検討　　　　　　　　　　　　　　　
及川 敬太, 古田 康, 永橋 立望, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
日本耳鼻咽喉科学会会報, 107, 4, 399, 399, (一社)日本耳鼻咽喉科学会, 2004年04月
日本語

Macrophage migration inhibitory factor in allergic rhinitis: Its identification in eosinophils at the site of inflammation
Y Nakamaru, D Takagi, N Oridate, Y Furuta, J Nishihira, S Fukuda
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 113, 3, 205, 209, ANNALS PUBL CO, 2004年03月, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study was to assess the potential role of macrophage migration inhibitory factor (MIF) in the pathogenesis of allergic rhinitis (AR). Serum MIF concentrations were measured by a specific enzyme-linked inummosorbent assay. In order to elucidate the cellular source of MIF, we performed double immunostaining of biopsy specimens of the nasal mucous membrane with markers for MIF and for inflammatory cells. The mean MIF level in sera from patients with AR was significantly higher than that in sera from healthy controls. Moreover, the levels were significantly correlated with the severity of the clinical symptoms. The majority of the MIF-positive cells at the site of allergic inflammation were eosinophils. These data suggest that MIF plays a role in the initiation and maintenance of AR. Eosinophils formed the largest population of MIF-producing cells; this finding suggests that they may be a major source of MIF at inflammatory sites in atopic disease.

The efficacy of Burow's solution as an ear preparation for the treatment of chronic ear infections
M Kashiwamura, E Chida, M Matsumura, Y Nakamaru, N Suda, Y Terayama, S Fukuda
OTOLOGY & NEUROTOLOGY, 25, 1, 9, 13, LIPPINCOTT WILLIAMS & WILKINS, 2004年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To determine the efficacy of Burow's solution as an otologic preparation for the treatment of chronic ear infection.
Study Design: Two studies were included: 1) a prospective clinical study and 2) a laboratory study on antibacterial and antifungal effects.
Setting: A private otology practice and a laboratory study.
Patients: Fifty-eight patients with refractory otorrhea. Intervention: Diagnosis by otoscopy, audiometry, and bacteriology.
Methods: Burow's solution was mixed in solutions with four organisms: methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, Candida albicans, and Aspergillus. Soon after Burow's solution was mixed in the solutions with organisms. and 5, 10, and 20 minutes thereafter, the mixtures were cultured on agars. The numbers of the bacterial or fungal colonies were counted to evaluate the effect of Burow's solution.
Main Outcome Measures: Changes in the clinical findings of the ears, the symptom of otorrhea, and side effects were assessed.
Results: Thirty-five (70%) of the 50 ears assessed were "cured" and 10 (20%) ears assessed were "improved." No significant side effect was observed. Regarding the laboratory study, the four organisms disappeared within 20 minutes after Burow's solution was mixed.
Conclusion: Burow's solution was considered to be an effective otologic preparation.

喉頭全摘に至った喉頭帯状疱疹の一例　　　　　　　　　　　　　　　
樋口 榮作, 中丸 裕爾, 大渡 隆一郎, 坂下 智博, 目須田 康, 本間 明宏, 古田 康, 福田 諭
耳鼻咽喉科免疫アレルギー, 21, 2, 80, 82, 日本耳鼻咽喉科免疫アレルギー学会, 2003年06月
日本語, 73歳男.咽頭痛が出現した.炎症所見と腎機能障害も認めた.造影CT所見では,左披裂部の腫脹と両頸部リンパ節の腫脹が認められた.病理組織所見では,一部の扁平上皮に中等度から高度の異型が認められた.咽頭痛が強く,喉頭もしくは下咽頭の悪性腫瘍を疑った.喉頭浮腫によると,思われる呼吸困難が出現したため,緊急気管切開術を行った.喘息発作,誤嚥を発症し,全身状態が悪化した.喉頭直達鏡下生検術を行った.臨床所見と経過,検査結果から,一側性第IX,X,XI脳神経麻痺を伴う喉頭帯状疱疹と確定診断した.気管食道分離による誤嚥の防止を目的とした喉頭全摘術を行った.術後経過は良好で退院した.その後現在まで経過良好である

頭頸部扁平上皮癌の放射線化学療法施行例におけるマクロファージ遊走阻止因子の発現の検討　　　　　　　　　　　　　　　
鈴木 章之, 中丸 裕爾, 本間 明宏, 永橋 立望, 折館 伸彦, 古田 康, 福田 諭
頭頸部腫瘍, 29, 2, 363, 363, (一社)日本頭頸部癌学会, 2003年05月
日本語

鼻副鼻腔inverted papilloma再発例の検討　　　　　　　　　　　　　　　
及川 敬太, 古田 康, 永橋 立望, 本間 明宏, 折舘 伸彦, 中丸 裕爾, 福田 諭
日本耳鼻咽喉科学会会報, 106, 4, 393, 393, (一社)日本耳鼻咽喉科学会, 2003年04月
日本語

Treatment of relapsing polychondritis
Yuji Nakamaru, Dai Takagi, Masanori Maeda, Yasushi Furuta, Satoshi Fukuda, Shiroh Maguchi
Journal of Otolaryngology of Japan, 106, 3, 185, 191, Oto-Rhino-Laryngological Society of Japan Inc., 2003年, ［査読有り］
日本語, 研究論文（学術雑誌）, Introduction: Relapsing polychondritis (RP) manifests as an inflammation of cartilaginous structures throughout the body. Since RP affects cartilage tissues and proteoglycan-rich structures, symptoms appear in the ear, nose, eye, joints, and respiratory system. Otolaryngologists are frequently involved in RP's initial diagnosis, since it is likely to affect the head and neck regions. The etiology of RP remains unknown and it is relatively uncommon, so appropriate treatment remains to be determined. We studied the clinical course and treatment response. Methods: We studied clinical courses in 12 cases of RP treated at our hospital in the 11 years from 1991 to 2001. Results: In 11 of the 12 cases, conventional steroid therapy was implemented. Five required steroid pulse therapy, and 7 immunosuppressive drugs to control the disease. Strong initial therapy such as steroid pulse therapy plus immunosuppressive drugs suppressed inflammation and decreased its relapse in severe RP patients. One patient could be controlled only with nonsteroidal antiinflammatory drugs. Side effects such as cataracts and diabetes from steroid therapy or pancytopenia from Dapson were found in some patients. All 12 are alive at present. Six were subsequently released from steroid therapy. Anti-type II collagen antibody was not useful as an indicator for treatment but helpful as one of a complementary factors for diagnosis. Conclusion: Manifestations of RP are sometimes self-limited, but in most cases, inflammation is recurrent, gradually worsening and finally becoming life-threatening. It is difficult to determine the severity of RP and choose appropriate treatment in its initial stage. Because severe RP cannot be controlled with conventional steroid therapy, strong therapy is indicated in initial treatment if patients have serious symptoms.

Otologic manifestations of Wegener's granulomatosis
D Takagi, Y Nakamaru, S Maguchi, Y Furuta, S Fukuda
LARYNGOSCOPE, 112, 9, 1684, 1690, LIPPINCOTT WILLIAMS & WILKINS, 2002年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective/Hypothesis: To evaluate the clinical features, treatment, and outcomes of otologic manifestations in Wegener's granulomatosis (WG) treated at Hokkaido University Graduate School of Medicine, Sapporo, Japan. Study Design: We retrospectively reviewed 15 cases of WG with ear involvement. Methods: Twenty-five patients with WG were treated at Hokkaido University Graduate School of Medicine between 1992 and 2001. Fifteen of these patients had otologic symptoms. We evaluated the clinical course, method of therapy, and outcomes in all cases. Diagnosis of WG was made when the patients had clinical findings and a positive titer of cytoplasmic pattern antineutrophil cytoplasmic antibodies (c-ANCA), or when there were clear histologic findings. We also present three case reports. Results: In 15 cases, the most frequent finding was chronic otitis media. Sensorineural hearing loss was present in 2 patients. In 7 patients whose otologic manifestations were the primary involvement of WG, all were confirmed positive for c-ANCA and were treated with glucocorticoids and immunosuppressive drugs. Three patients who could be treated within 1 month of symptom onset showed marked improvement. Conclusions: In localized cases, biopsy specimens are often small, and it is frequently difficult to make a histologic diagnosis. The prognosis for hearing was poor when appropriate treatment was not given in the early stages of the disease. Therefore, WG should be included in the differential diagnosis in cases of atypical inflammatory states of the ear. Early diagnosis and appropriate treatment are important to prevent irreversible changes in the middle ear and inner ear.

Clonotypic analysis of T cells accumulating at arthritic lesions in HTLV-I env-pX transgenic rats
T Sugaya, A Ishizu, H Ikeda, Y Nakamaru, K Fugo, M Higuchi, H Yamazaki, K Imai, T Yoshiki
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 72, 1, 56, 61, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2002年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Human T cell leukemia virus type I (HTLV-I) env-pX transgenic rat, (env-pX rats) develop chronic destructive arthritis resembling rheumatoid arthritis in humans. Immunological characteristics were compared with those of collagen-induced arthritis (CIA). Rheumatoid factor was present in some env-pX rats regardless of the development of arthritis, but not in nontransgenic rats with CIA. All rats with CIA produced anti-type It collagen (IIC) antibody, but never so in env-pX rats with naturally occurring arthritis. Although expansions of oligoclonal T cells were evident in the affected joints, no particular clone was shown to infiltrate into the arthritic lesions in env-pX rats. In contrast to CIA. in which clonal expansions of IIC-specific T cells are implicated, locally expanded T cell clones against various antigens of the joints may play pathogenetic roles in the arthritis seen in env-pX rats. However, complementarity-determining region 3 of the TCR Vbeta gene of T cells accumulating at the affected joints in env-pX rats contained the GGA amino acid sequence, which was reported to be a conserved motif in HTLV-I env-pX transgenic mice with arthritis. These findings suggest that common antigens) might be recognized by T cells accumulating at sites of arthritis in both transgenic rats and mice. (C) Elsevier Science.

A case of invasive aspergillosis of the paranasal sinuses with a feature of allergic Aspergillus sinusitis
Y Nakamaru, S Fukuda, S Maguchi, D Takagi, Y Inuyama
OTOLARYNGOLOGY-HEAD AND NECK SURGERY, 126, 2, 204, 205, MOSBY, INC, 2002年02月, ［査読有り］
英語, 研究論文（学術雑誌）

Diagnosis of the elongated styloid process by three-dimensional computed tomography
Y Nakamaru, S Fukuda, S Miyashita, M Ohashi
AURIS NASUS LARYNX, 29, 1, 55, 57, ELSEVIER SCI LTD, 2002年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To examine whether the styloid process can be imaged by three-dimensional Computer tomography reconstruction (3-DCT) distinctly enough to be used for diagnosis, and whether the image findings are explanatory of the symptoms. Methods: We performed 3-DCT in four patients suspected to have elongated styloid process in Our hospital. The apparatus we used was X-vigor (Toshiba), and the processing software was X-tension; the slicing thickness was 1.0 min and the shifting speed of CT table was 1.0 mm per rotation. One hundred and twenty images were reconstructed for a view. Results: In all cases. the 3-DCT showed the exact full length or the styloid process. Two cases were diagnosed as elongation of the styloid process by 3-DCT and their image findings were explanatory of the symptoms. In other two cases, the 3-DCT showed no difference between the right and the left styloid processes, and thus the diagnosis of elongation of the styloid process had to be excluded. Conclusion: We suggest that 3-DCT is useful for the diagnosis, explanation to patients and selection of treatment in some cases of elongated styloid process, but further study in more cases is required before we can fully confirm the utility. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Correlation between the levels of circulating adhesion molecules and PR3-ANCA in Wegener's granulomatosis
M Takizawa, S Maguchi, Y Nakamaru, Y Miyatake, S Fukuda, Y Inuyama
AURIS NASUS LARYNX, 28, S59, S62, ELSEVIER SCI LTD, 2001年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: The adhesion of neutrophils to the vascular endothelial cells appears to be important for the pathogenesis of vasculitis in Wegener's granulomatosis (WG). To determine the pathological significance of the neutrophil adhesion, we have examined and evaluated the relationships between the levels of adhesion molecules and proteinase-3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA), and between the levels of TNF-a and disease activities in WG.
Methods: sELAM-1 and sICAM-1 in sera from WG and healthy donors were detected by ELISA. SLe(x) and LFA-1 on neutrophils were detected by flow cytometry.
Results: The level of sICAM-1 was significantly higher in active WG than in inactive WG, tending to reflect individual disease activities. There was no difference in the level of sELAM-1 between WG patients and healthy donors.
Conclusion: Our study suggests that the adhesion of neutrophils to the vascular endothelium is significant for the pathogenesis of the vasculitis in WG. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

両側性ムンプス難聴の1例　　　　　　　　　　　　　　　
水町 貴諭, 福田 諭, 千田 英二, 中丸 裕爾, 黒田 努, 犬山 征夫, 間口 四郎
日本耳鼻咽喉科学会会報, 104, 1増刊, 77, 77, (一社)日本耳鼻咽喉科学会, 2001年01月
日本語

Immunological hyperresponsiveness in HTLV-1 LTR-env-pX transgenic rats: A prototype animal model for collagen vascular and HTLV-I-related inflammatory diseases
Y Nakamaru, A Ishizu, H Ikeda, T Sugaya, K Fugo, M Higuchi, H Yamazaki, T Yoshiki
PATHOBIOLOGY, 69, 1, 11, 18, KARGER, 2001年, ［査読有り］
英語, 研究論文（学術雑誌）, We have earlier reported that diverse collagen vascular diseases, including arthritis, arteritis, thrombosis, myocarditis, myositis, sialo-/dacryoadenitis and dermatitis develop with the advent of autoantibodies in transgenic rats carrying the LTR-env-pX gene of human T lymphocyte virus type I (LTR-env-pX rats). To clarify the pathogenesis of these collagen vascular diseases, immunological features of LTR-env-pX rats were examined. In LTR-env-pX rats affected with these diseases, expression of CD80/86 on both tissue-infiltrating and peripheral T cells increased, compared with findings in non-transgenic rats with experimental inflammatory diseases. CD80/86 was also upregulated on peripheral T cells in LTR-env-pX rats prior to the development of diseases. Lymphocytes from LTR-env-pX rats showed an increase in autologous proliferation and were hyperreactive against several mitogens, including concanavalin A, immobilized anti-CD3 antibodies, and superantigens in vitro. Anti gen-specific immune response was also enhanced in LTR-env-pX rats. The collective evidence indicates that lymphocytes of LTR-env-pX rats constitutively express surface molecules related to T cell activation and are immunologically hyperresponsive. Bone marrow cell transfer from LTR-env-pX rats to lethally irradiated non-transgenic rats revealed that these immunologically pre-activated and hyperresponsive lymphocytes play a critical role in the pathogenesis of several collagen vascular diseases, especially of dermatitis in LTR-env-pX rats. Copyright (C) 2001 S. Karger AG, Basel.

Models of HTLV-I-induced diseases. Infectious transmission of HTLV-I in inbred rats and HTVL-I env-pX transgenic rats.
T Yoshiki, H Ikeda, U Tomaru, O Ohya, T Kasai, I Yamashita, K Morita, H Yamazaki, A Ishizu, Y Nakamaru, K Kikuchi, S Tanaka, A Wakisaka
Leukemia, 11 Suppl 3, 245, 6, 1997年04月, ［国際誌］
英語, 研究論文（学術雑誌）, To examine the pathogenic roles of HTLV-I in HTLV-I-induced diseases, we developed two models; namely HTLV-I carrier rats and HTLV-I env-pX transgenic rats. Among life long HTLV-I carriers in seven rat strains, only WKAH rats with the RT1k haplotype developed chronic progressive myeloneuropathy, resembling HAM/TSP clinically and histologically in humans, designated as HAM rat disease and after long incubation periods. Apoptosis of myelin forming cells, oligodendrocytes and Schwann cells associated with HTLV-I infection appears to be the primary cause of HAM rat disease. Local activation of the pX gene and TNF alpha gene was evident in these rats. WKAH rats transgenic for HTLV-I env-pX gene were established and at age 5 weeks, swelling of the bilateral ankle joints began to develop and histological features of the affected joints resembled findings in cases of rheumatoid arthritis (RA): high-titers of rheumatoid factors were present in these rats. A series of vascular collagen diseases such as polyarteritis nodosa-like angiitis, polymyositis, myocarditis, and Sjögren's syndrome-like sialodenitis together with RA were present, even in one individual animal. These transgenic rats as well as HAM rats appear to be suitable animal models for elucidating pathogenic mechanisms implicated in HTLV-I-induced diseases and also various demyelinating vascular collagen diseases of unknown etiology.

A wide spectrum of collagen vascular and autoimmune diseases in transgenic rats carrying the env-pX gene of human T lymphocyte virus type I.
Yamazaki H, Ikeda H, Ishizu A, Nakamaru Y, Sugaya T, Kikuchi K, Yamada S, Wakisaka A, Kasai N, Koike T, Hatanaka M, Yoshiki T
Int Immunol, 9, 2, 339, 346, 1997年02月, ［査読有り］
英語, 研究論文（学術雑誌）

The association between human leukocyte antigens (HLA) and cytoplasmic-antineutrophil cytoplasmic antibody (cANCA)-positive Wegener's granulomatosis in a Japanese population
Y. Nakamaru, S. Maguchi, M. Takizawa, S. Fukuda, Y. Inuyama
Rhinology, 34, 3, 163, 165, 1996年09月, ［査読有り］
英語, 研究論文（学術雑誌）, The present study examined the association between various human leukocyte antigens (HLA) and cytoplasmic-antineutrophil cytoplasmic antibody (cANCA)-positive Wegener's granulomatosis (WG) in Japanese subjects to determine whether HLA antigens are involved in the pathogenesis of this disease. The study involved 16 subjects with cANCA-positive WG treated in our department. HLA-typing of the lymphocytes was performed using a lymphocyte microcytotoxicity assay. Of the subjects with cANCA-positive WG, 62.5% (10/16) were positive for HLA-DR9, as compared to 26% of the healthy control subjects. This HLA-DR9 elevation was statistically significant (p <
0.01, Pc <
0.05)
were also noted a weaker association between HLA-B55 and cANCA-positive WG (p <
0.05). The results indicate that an association may exist between certain HLA-class allotypes and WG.

Wegener 肉芽腫症の治療とネフロスカラー・C-ANC による抗好中球細胞質抗体価の変動
間口 四郎, 滝沢 昌彦, 宮武 由甲子, 中丸 裕爾, 福田 諭, 犬山 征夫
日本耳鼻咽喉科學會會報, 98, 6, 974, 983, The Oto-Rhino-Laryngological Society of Japan, Inc., 1995年06月20日
日本語, 保険適用となったネソロスカラー・C ANCによる抗好中球細胞質抗体の測定は従来の間接蛍光抗体法に比べ若干感度が低かったが, 特異性の高さ, 定量性, 簡便性などからWegener肉芽腫症 (WG) の診断, 治療に有用であった. WGの治療においては, 免疫抑制療法において多くの例で抗体価は低下し, 病状の軽快と平行し推移し有用なマーカーであった. しかしながら, cANCA再上昇は必ずしも再発を意味せず, その治療の変更は実際の症状増悪の後開始するのが良いと考えた. WGの治療に関しては従来の標準的免疫抑制療法以外の治療法も有用であり, 治療法の選択は症例個々の状況に応じたstage adapted treatmentが望まれると考えた.

縦隔内転移をきたした喉頭癌3症例
柏村 正明, 山田 和之, 檜山 繁樹, 福田 諭, 間口 四郎, 依田 明治, 中丸 裕爾, 犬山 征夫
耳鼻咽喉科臨床, 88, 2, 219, 224, The Society of Practical Otolaryngology, 1995年02月01日
日本語, Mediastinal metastasis of or invasion by laryngeal carcinoma is not common. If it is not found in the early stage and treated, it causes miserable symptoms such as tracheal stenosis or intratrachal hemorrhage. We treated three patients with laryngeal carcinoma with mediastinal metastasis or invasion. The primary lesion was subglottic in two and glottic in one. The clinical course and some examination results suggested that two patients had metastases and one had direct invasion.
We concluded that patients with laryngeal cancer, especially subglottic, should be examined for mediastinal, as well as cervical lymphnode metastasis, as soon as possible. We otolaryngologists should be able to find mediastinal lesions early using examinations such as CT scans.

当科における鼻骨骨折症例の検討
中丸 裕爾, 本間 明宏, 飯塚 桂司
耳鼻咽喉科・頭頸部外科, 65, 9, 745, 748, (株)医学書院, 1993年09月
日本語, 6年間に受診した鼻骨骨折症例について,成因と治療内容に対する満足度等につきアンケート調査を行った。鼻骨骨折の成因では,暴行,交通事故,スポーツの順に多く,それぞれの項目につき更に詳しく成因を検討した。治療に対するアンケートでは,整復後の外観に関しては,83%の患者が満足しているが,約1/3の患者が鼻閉感を訴えた。固定に関しては,内固定に関する不満が多く,固定期間は4日,外固定は7日程度が苦痛を与えないという面ではよい

Interavascular papillary endothelial hyperplasia例
中丸 裕爾, 飯塚 桂司, 本間 明宏
耳鼻咽喉科臨床, 86, 12, 1747, 1751, 耳鼻咽喉科臨床学会, 1993年
英語, 研究論文（学術雑誌）, A 72-year-old woman had noted left submandibular swelling for 7 years. On examination a 5 × 5 cm smooth, hard, fixed, painless mass was palpable in the left submandibular area. CT scan showed a circumscribed, isodense mass near the bifurcation of the carotid artery. Extirpation of the tumor was performed. The pathological diagnosis was intravascular papillary endothelial hyperplasia. The postoperative course was good, and the patient remains free of disease more than 5 months after surgery. Intravascular papillary endothelial hyperplasia is characterized by intravascular endothelial proliferation that resembles angiosarcoma. This disease seems to be the result of a peculiar process of thrombus undergoing organization. The prognosis is good, and the treatment is usually total extirpation of the tumor. © 1993, The Society of Practical Otolaryngology. All rights reserved.

好酸球性副鼻腔炎up-to-date-病態解明と最適な治療をめざして《病態》オーバーラップする疾患との関わり 好酸球性多発血管炎性肉芽腫症(EGPA),IgG4関連疾患などを中心に
鈴木正宣, 中丸裕爾, 耳鼻咽喉科・頭頚部外科, 93, 1, 2021年

口腔アレルギー症候群-診断と治療-口腔アレルギーに対する免疫療法
鈴木正宣, 中丸裕爾, Monthly Book ENTONI, 254, 2021年

鼻中隔尾側弯曲(前弯)の客観的評価と適切な鼻中隔矯正術の術式選択
木村将吾, 中丸裕爾, 鈴木正宣, 本間あや, 中薗彬, 本間明宏, 日本耳鼻咽喉科学会会報, 124, 4, 2021年

Endoscopic Medial Maxillectomy With Preservation of Inferior Turbinateを用いて摘出した上顎洞血瘤腫の1例
佐藤孝大, 中丸裕爾, 鈴木正宣, 本間あや, 木村将吾, 本間明宏, 耳鼻咽喉科臨床 補冊, 157, 2021年

鼻内内視鏡と開頭の併用による前頭蓋底手術の1例
和田侑也, 和田侑也, 鈴木正宣, 中丸裕爾, 本間あや, 山田真司, 本間明宏, 耳鼻咽喉科臨床 補冊, 157, 2021年

前頭開頭術後に生じた前頭蓋底粘液嚢胞に対して内視鏡下鼻副鼻腔手術が有用であった2症例
山田真司, 鈴木正宣, 中丸裕爾, 本間明宏, 耳鼻咽喉科臨床 補冊, 157, 2021年

両視力障害で発症した多発血管炎性肉芽腫症(GPA)
吉村淳, 鈴木正宣, 中丸裕爾, 鈴木崇祥, 本間あや, 中薗彬, 木村将吾, 本間明宏, 中里信一, 岡田宏美, 耳鼻咽喉科臨床, 114, 2, 2021年

鼻腔内視鏡手術手技計測システムの開発
宮路洸, 鈴木正宣, 中丸裕爾, 佐瀬一弥, CHEN Xiaoshuai, 辻田哲平, 小水内俊介, 本間明宏, 近野敦, 計測自動制御学会北海道支部学術講演会論文集, 53rd, 2021年

下鼻甲介shoulder osteotomyを行った狭鼻の1例
田中大地, 中丸裕爾, 鈴木正宣, 本間あや, 中薗彬, 木村将吾, 本間明宏, 耳鼻咽喉科・頭頚部外科, 93, 6, 2021年

耳鼻咽喉科診療Q&A【鼻科領域 21】術後や鼻出血での鼻パッキングの適応はどう考えますか?する場合の材料としては何が適切ですか?
鈴木正宣, 中丸裕爾, JOHNS, 36, 9, 2020年

篩骨動脈に基づく鼻中隔粘膜弁を用いる鼻中隔穿孔閉鎖術の1例
勝俣量平, 鈴木正宣, 中薗彬, 中丸裕爾, 本間明宏, 耳鼻咽喉科・頭頚部外科, 92, 9, 2020年

低亜鉛が鼻粘膜のサイトカイン産生と炎症細胞浸潤に及ぼす影響
鈴木正宣, 中丸裕爾, 本間あや, 中薗彬, 木村将吾, RAMENZANPOIR Mahnaz, VREUGDE Sarah, WORMALD Peter-John, 本間明宏, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 38th, 2020年

アレルギー性鼻炎患者の睡眠と内因性メラトニンの評価
本間あや, 本間あや, SUNKARANENI Vishnu S, SKENE Debra J, 鈴木正宣, 中丸裕爾, 本間明宏, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 38th, 2020年

狭鼻を伴うアレルギー性鼻炎,慢性副鼻腔炎に対して下甲介shoulder osteotomyを施行した1例
田中大地, 中丸裕爾, 鈴木正宣, 本間あや, 中薗彬, 木村将吾, 本間明宏, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 38th, 2020年

嗅神経芽細胞腫に対する内視鏡頭蓋底外科
茂木洋晃, 山口秀, 伊師雪友, 岡本迪成, 澤谷亮介, 中薗彬, 鈴木正宣, 中丸裕爾, 本間明宏, 日本神経内視鏡学会プログラム・抄録集, 27th, 2020年

Anti mumps igm antibody positive rate with sudden sensorineural hearing loss using second generation enzyme immunoassay : A retrospective, multi-institutional investigation in hokkaido, Japan
Atsushi Fukuda, Shinya Morita, Yuji Nakamaru, Kimiko Hoshino, Keishi Fujiwara, Shigeru Akazawa, Tomohiro Sakashita, Nobuyuki Obara, Akihiro Homma, Journal of Otolaryngology of Japan, 122, 9, 1267, 1268, 2019年
Oto-Rhino-Laryngological Society of Japan Inc., 日本語, 速報，短報，研究ノート等（学術雑誌）

鼻閉にまつわる問題とその解決策 鼻閉の原因と治療 1-鼻腔 鼻腔腫瘍
鈴木正宣, 中丸裕爾, JOHNS, 35, 11, 2019年

当院における外鼻形成術および鼻中隔矯正術施行例の検討
木村将吾, 中丸裕爾, 鈴木正宣, 本間あや, 中薗彬, 本間明宏, 日本鼻科学会会誌(Web), 58, 3, 2019年

ANCA関連血管炎性中耳炎における好中球細胞外トラップの測定と臨床応用
森田真也, 中丸裕爾, 鈴木正宣, 本間明宏, 耳鼻咽喉科免疫アレルギー(Web), 37, 2, 2019年

鼻粘膜において低亜鉛はコラーゲン産生を抑制する
鈴木正宣, 鈴木正宣, 中丸裕爾, RAMEZANPOUR Mahnaz, 中薗彬, WORMALD Peter-John, VREUGDE Sarah, 本間明宏, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 37th, 2019年

鼻粘膜において低亜鉛はコラーゲン産生を抑制する
鈴木正宣, 鈴木正宣, 中丸裕爾, RAMEZANPOUR Mahnaz, 中薗彬, WORMALD Peter-John, VREUDGE Sarah, 本間明宏, 耳鼻咽喉科免疫アレルギー(Web), 37, 2, 2019年

嗅神経芽細胞腫の進行度に応じた治療戦略決定のための新分類の提唱
茂木洋晃, 山口秀, 伊師雪友, 遠藤将吾, 小林浩之, 寺坂俊介, 鈴木正宣, 中丸裕爾, 本間明宏, 宝金清博, 日本脳腫瘍学会プログラム・抄録集, 37th, 2019年

鼻粘膜上皮細胞においてSIRT-1はPolyICに誘導されるMMP9を負に制御する
鈴木正宣, 鈴木正宣, 中丸裕爾, 高木大, 本間あや, VREUGDE Sarah, WORMALD Peter-John, 本間明宏, 耳鼻咽喉科免疫アレルギー(Web), 36, 2, 2018年

篩骨動脈を茎とする鼻中隔粘膜弁を用いた鼻中隔穿孔閉鎖術の1例
勝俣量平, 鈴木正宣, 中薗彬, 中丸裕爾, 本間明宏, 日本鼻科学会会誌(Web), 57, 3, 2018年

当院における嗅神経芽細胞腫の治療方針と成績
中薗彬, 中丸裕爾, 鈴木正宣, 水町貴諭, 高木大, 本間明宏, 日本鼻科学会会誌(Web), 57, 3, 2018年

Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2
Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, Toshifumi Yamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubor, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase, CYTOKINE, 100, 83, 83, 2017年12月
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 英語, 研究発表ペーパー・要旨（国際会議）

【手術に必要な画像診断-鼻編】 その他の疾患に対する鼻科手術 鼻副鼻腔良性腫瘍　　　　　　　　　　　　　　　
中丸 裕爾, JOHNS, 33, 7, 891, 894, 2017年07月
(株)東京医学社, 日本語

当科の弛緩部型中耳真珠腫の臨床的検討　　　　　　　　　　　　　　　
福田 篤, 森田 真也, 干野 季美子, 藤原 圭志, 中丸 裕爾, 福田 諭, 日本耳鼻咽喉科学会会報, 120, 4, 535, 535, 2017年04月
(一社)日本耳鼻咽喉科学会, 日本語

IgG4関連疾患における鼻副鼻腔病変の検討
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭, 日本耳鼻咽喉科学会会報, 120, 4, 557, 557, 2017年04月
(一社)日本耳鼻咽喉科学会, 日本語

外耳道癌組織における免疫組織化学的手法に基づく発現分子解析　　　　　　　　　　　　　　　
森田 真也, 本間 明宏, 中丸 裕爾, 安川 真一郎, 福田 篤, 福田 諭, 日本耳鼻咽喉科学会会報, 120, 4, 566, 566, 2017年04月
(一社)日本耳鼻咽喉科学会, 日本語

【おとなのかぜ、こどものかぜ】 おとなのかぜ 上・下気道症状を有するかぜの診断と治療 鼻汁・鼻閉型
中丸 裕爾, JOHNS, 33, 1, 51, 53, 2017年01月
(株)東京医学社, 日本語

13歳発症の再発性多発軟骨炎　　　　　　　　　　　　　　　
西村 弘基, 戸澤 雄介, 植木 将弘, 竹崎 俊一郎, 山田 雅文, 有賀 正, 中丸 裕爾, 三橋 智子, 中山 加奈子, 山本 さやか, 原 和也, 鎌田 晃嘉, 鈴木 雅彦, 八鍬 聡, 那須 敬, 植竹 公明, 日本小児科学会雑誌, 121, 1, 119, 119, 2017年01月
(公社)日本小児科学会, 日本語

HLAクラスI認識受容体群LILRの新展開 病原微生物によって壊された抗体を認識する生体防御機構
平安 恒幸, 齋藤 史路, 末永 忠広, 信田 京子, 荒瀬 規子, 及川 敬太, 山岡 俊文, 室田 浩之, 知花 博治, 中川 一路, 久堀 智子, 永井 宏樹, 中丸 裕爾, 片山 一朗, Colonna Marco, 荒瀬 尚, MHC: Major Histocompatibility Complex, 23, 2Suppl., 95, 95, 2016年10月
日本組織適合性学会, 日本語

MRIで骨に異常信号を認めた再発性多発軟骨炎の小児例　　　　　　　　　　　　　　　
戸澤 雄介, 山田 雅文, 植木 将弘, 竹崎 俊一郎, 中丸 裕爾, 中山 加奈子, 山本 さやか, 原 和也, 鎌田 晃嘉, 鈴木 雅彦, 八鍬 聡, 那須 敬, 植竹 公明, 三橋 智子, 有賀 正, 日本小児リウマチ学会総会・学術集会プログラム・抄録集, 26回, 124, 124, 2016年10月
(一社)日本小児リウマチ学会, 日本語

HLAクラスI認識受容体群LILRの新展開 病原微生物によって壊された抗体を認識する生体防御機構　　　　　　　　　　　　　　　
平安 恒幸, 齋藤 史路, 末永 忠広, 信田 京子, 荒瀬 規子, 及川 敬太, 山岡 俊文, 室田 浩之, 知花 博治, 中川 一路, 久堀 智子, 永井 宏樹, 中丸 裕爾, 片山 一朗, Colonna Marco, 荒瀬 尚, MHC: Major Histocompatibility Complex, 23, 2Suppl., 95, 95, 2016年10月
日本組織適合性学会, 日本語

Circadian rhythm in the nasal mucosa: the effect of dexamethasone and allergic rhinitis on the nasal clock
A. Honma, Y. Yamada, Y. Nakamaru, D. Takagi, M. Suzuki, S. Fukuda, K. -I. Honma, S. Honma, JOURNAL OF SLEEP RESEARCH, 25, 108, 109, 2016年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

アレルギー性鼻炎モデルマウスにおける鼻粘膜時計遺伝子発現リズム　　　　　　　　　　　　　　　
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭, 日本鼻科学会会誌, 55, 3, 468, 468, 2016年09月
(一社)日本鼻科学会, 日本語

【喘息と耳鼻咽喉科疾患】 アレルギー性鼻炎と気管支喘息の関連　　　　　　　　　　　　　　　
中丸 裕爾, ENTONI, 197, 7, 12, 2016年09月
アレルギー性鼻炎と喘息は同一の気道に生じるため、多くの類似点を持つ。鼻炎患者における喘息の合併頻度は10〜40%、逆に喘息患者における鼻炎の合併率は85〜95%と非常に高い。また鼻炎症状と喘息症状には有意な相関がある。組織学的に両疾患は、粘膜構成細胞、浸潤してくる炎症細胞、サイトカイン、ケモカインなどの液性因子など多くの類似点がある。また下気道、上気道それぞれ一方の誘発で他方の粘膜にアレルギー性炎症が惹起される。このため、一方の疾患を治療するだけでは、患者全体のアレルギー性炎症の軽快につながらない。鼻噴霧用ステロイド治療は喘息症状を軽快させるが、喘息の治療を減弱できるほどの効果は認められず、両疾患の治療をそれぞれの至適用量で行う必要がある。アレルギー性鼻炎を治療する際には喘息のコントロール、新規発症の有無を考慮し、相談できる呼吸器内科医を確保しておくことも重要と考える。(著者抄録), (株)全日本病院出版会, 日本語

中耳真珠腫の術前MRI拡散強調像の検討 T1強調像併用による診断精度向上の試み
福田 篤, 森田 真也, 藤原 圭志, 中丸 裕爾, 福田 諭, Otology Japan, 26, 4, 353, 353, 2016年09月
(一社)日本耳科学会, 日本語

隣接構造物の破壊を伴う外耳道真珠腫症例の検討　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 福田 篤, 福田 諭, Otology Japan, 26, 4, 495, 495, 2016年09月
(一社)日本耳科学会, 日本語

グルココルチコイドによる鼻粘膜末梢時計の調整 PER2発光リズムを指標とした解析
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 本間 研一, 本間 さと, 福田 諭, 耳鼻咽喉科免疫アレルギー, 34, 2, 56, 57, 2016年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

好酸球性多発血管炎性肉芽腫症(EGPA)の耳症状
中丸 裕爾, 高木 大, 鈴木 正宣, 本間 あや, 福田 諭, 耳鼻咽喉科免疫アレルギー, 34, 2, 139, 139, 2016年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

IgG4関連疾患における鼻副鼻腔病変の検討
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭, 耳鼻咽喉科免疫アレルギー, 34, 2, 179, 180, 2016年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

次世代遺伝子シークエンサーを用いた、鼻副鼻腔内反性乳頭腫の悪性転化に関与する変異遺伝子の解析　　　　　　　　　　　　　　　
安川 真一郎, 畠山 博充, 鈴木 崇祥, 水町 貴諭, 中丸 裕爾, 本間 明宏, 福田 諭, 頭頸部癌, 42, 2, 220, 220, 2016年05月
日本頭頸部癌学会, 日本語

膠原病・自己免疫疾患 膠原病と自己炎症性疾患 IgG4関連疾患における鼻副鼻腔病変の検討　　　　　　　　　　　　　　　
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭, アレルギー, 65, 4-5, 557, 557, 2016年05月
(一社)日本アレルギー学会, 日本語

通年性アレルギー性鼻炎 鼻粘膜概日リズムを指標としたアレルギー性鼻炎の時間治療　　　　　　　　　　　　　　　
本間 あや, 中丸 裕爾, 高木 大, 福田 諭, 本間 研一, 本間 さと, アレルギー, 65, 4-5, 586, 586, 2016年05月
(一社)日本アレルギー学会, 日本語

喘息患者における副鼻腔CT所見とバイオマーカーの検討 喫煙が及ぼす影響　　　　　　　　　　　　　　　
木村 孔一, 今野 哲, 中丸 裕爾, 牧田 比呂仁, 谷口 菜津子, 清水 薫子, 木村 裕樹, 鈴木 雅, 小野 純也, 太田 昭一郎, 出原 賢治, 西村 正治, アレルギー, 65, 4-5, 654, 654, 2016年05月
(一社)日本アレルギー学会, 日本語

隣接構造物の破壊を伴う外耳道真珠腫症例の検討　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 福田 篤, 福田 諭, 日本耳鼻咽喉科学会会報, 119, 4, 599, 599, 2016年04月
(一社)日本耳鼻咽喉科学会, 日本語

当科における中耳真珠腫の術前MRI拡散強調像の検討
福田 篤, 森田 真也, 中丸 裕爾, 福田 諭, 日本耳鼻咽喉科学会会報, 119, 4, 603, 603, 2016年04月
(一社)日本耳鼻咽喉科学会, 日本語

PERIOD2発光リズムを指標とした鼻粘膜末梢時計機構の解析
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 福田 諭, 本間 研一, 本間 さと, 日本耳鼻咽喉科学会会報, 119, 4, 636, 636, 2016年04月
(一社)日本耳鼻咽喉科学会, 日本語

【アレルギー疾患と睡眠】 鼻粘膜末梢時計リズムを指標としたアレルギー性鼻炎の時間治療法
本間 あや, 中丸 裕爾, 本間 さと, 睡眠医療, 10, 1, 109, 112, 2016年03月
アレルギー性鼻炎の症状は早期増悪し、体内時計による制御が示唆される。また、鼻炎症状の治療法にステロイド局所投与があるが、グルココルチコイドは生体内の多くの末梢時計において同調因子として作用することが知られており、治療効果に影響を来す可能性が推測される。われわれは、マウス鼻粘膜における時計遺伝子Period(Per)2の発現を発光レポーターを用いて解析し、鼻粘膜が概日時計をもち、グルココルチコイドが同調因子であることを明らかにした。ステロイド局所投与は、鼻粘膜末梢時計を脱同調させない時刻が望ましく、昼行性のヒトの場合は夕方に相当することが判明した。時間治療は、概日リズムに着目して薬物を効果的に利用する治療法であり、今後のさらなる展開が期待される。(著者抄録), (株)ライフ・サイエンス, 日本語

Surgical Therapy Reduces Blood Eosinophil Counts in Eosinophilic Chronic Rhinosinusitis
Dai Takagi, Yuji Nakamaru, Satoshi Fukuda, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 137, 2, AB64, AB64, 2016年02月
MOSBY-ELSEVIER, 英語, 研究発表ペーパー・要旨（国際会議）

Regulation of IL-4 Gene Expression By SIRT1 in Human Mast Cell
Yuji Nakamaru, Dai Takagi, Satoshi Fukuda, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 137, 2, AB75, AB75, 2016年02月
MOSBY-ELSEVIER, 英語, 研究発表ペーパー・要旨（国際会議）

HLAクラスI認識受容体群LILRの新展開-病原微生物によって壊された抗体を認識する生体防御機構-
平安恒幸, 齋藤史路, 末永忠広, 末永忠広, 信田京子, 荒瀬規子, 荒瀬規子, 及川敬太, 山岡俊文, 室田浩之, 知花博治, 中川一路, 久堀智子, 永井宏樹, 中丸裕爾, 片山一朗, COLONNA Marco, 荒瀬尚, 荒瀬尚, MHC (Web), 23, 2 Suppl, 2016年

Sinus Computed Tomographic Findings In Smoking And Non-Smoking Asthmatics: Associations With Asthma-Related Indices And Biomarkers Analysis
H. Kimura, S. Konno, Y. Nakamaru, H. Makita, H. Kimura, N. Taniguchi, K. Shimizu, M. Suzuki, J. Ono, K. Izuhara, M. Nishimura, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 193, 2016年
AMER THORACIC SOC, 英語, 研究発表ペーパー・要旨（国際会議）

アレルギー性鼻炎モデルマウスにおける鼻粘膜時計遺伝子発現リズム
本間あや, 中丸裕爾, 高木大, 鈴木正宣, 福田諭, 日本鼻科学会会誌(Web), 55, 3, 2016年

IgG4関連疾患における鼻副鼻腔病変の検討
高木大, 中丸裕爾, 鈴木正宣, 本間あや, 福田諭, 耳鼻咽喉科免疫アレルギー(Web), 34, 2, 2016年

グルココルチコイドによる鼻粘膜末梢時計の調整:PER2発光リズムを指標とした解析
本間あや, 本間あや, 中丸裕爾, 高木大, 鈴木正宣, 本間研一, 本間さと, 福田諭, 耳鼻咽喉科免疫アレルギー(Web), 34, 2, 2016年

好酸球性多発血管炎性肉芽腫症(EGPA)の耳症状
中丸裕爾, 高木大, 鈴木正宣, 本間あや, 福田諭, 耳鼻咽喉科免疫アレルギー(Web), 34, 2, 2016年

副鼻腔炎を合併したIgG4関連疾患症例
高木 大, 中丸 裕爾, 鈴木 正宣, 本間 あや, 福田 諭, アレルギーの臨床, 35, 11, 1090, 1092, 2015年10月
症例は47歳女性。1年前からの嗅覚障害、鼻閉、顎下腺腫脹を主訴に当科受診。両側涙腺腫脹、顎下腺の腫脹も認められた。両側鼻内にポリープがみられ、副鼻腔CTの所見は、両側ともに篩骨洞優位の副鼻腔炎の所見が認められた。消化器病変は認めなかった。血清IgGは1800mg/dlと上昇しており、血清IgG4は797mg/dlと著明な上昇が認められた。鼻内からの組織所見と合わせてIgG4関連疾患と診断した。ステロイドの内服はせず、ステロイド点鼻、吸入薬にて治療し、症状は改善した。IgG4関連疾患における副鼻腔炎の合併は比較的頻度が高く、診療の際には鼻副鼻腔のチェックも必要である。(著者抄録), (株)北隆館, 日本語

Sirtuin 1 modulates IL-4 gene expression in human mast cell
Y. Nakamaru, D. Takagi, S. Fukuda, ALLERGY, 70, 445, 445, 2015年09月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Differentiation of squamous cell carcinoma and inverted papilloma using non-invasive MR perfusion imaging
N. Fujima, Y. Nakamaru, T. Sakashita, A. Homma, A. Tsukahara, K. Kudo, H. Shirato, DENTOMAXILLOFACIAL RADIOLOGY, 44, 9, 2015年09月
Objectives: To investigate the diagnostic value of tumour blood flow (TBF) obtained with pseudocontinuous arterial spin labelling for the differentiation of squamous cell carcinoma (SCC) and inverted papilloma (IP) in the nasal or sinonasal cavity.
Methods: We retrospectively analysed the cases of 33 patients with SCC and 8 patients with IF in the nasal or sinonasal cavity. Pseudocontinuous arterial spin labelling scanning was performed for all patients using a 3.0-T MR unit. Quantitative TBF values were measured by two neuroradiologists by respectively delineating the whole-tumour regions of interest, and the mean of them was determined as TBF value in each patient. Additionally, the presence of imaging findings of convoluted cerebriform pattern (CCP) on MR T-2 weighted images was determined in all patients. As a subgroup analysis, patients with IF were divided into aggressive and non-aggressive IPs depending on their progression range. First, an intraclass correlation coefficient (ICC) of TBF values between two neuroradiologists was determined. Next, a statistical comparison of the TBF value by a Mann-Whitney U test between the patients with SCC and IP was performed. Additionally, the comparison by an ANOVA with a post hoc test of Tukey's method among the SCC, non-aggressive IF and aggressive IP groups was also performed. If significance was observed, the diagnostic accuracy to differentiate SCCs from IPs was calculated. Diagnostic accuracy by CCP findings alone and by the combination of CCP findings and TBF were also assessed.
Results: The ICC of TBF values between two neuroradiologists was 0.82. The mean TBF values in the patients with SCC, all patients with IP, those with aggressive IP and those with non-aggressive IP were 141.2 +/- 33.1, 77.8 +/- 31.5, 109.4 +/- 16.7 and 58.8 +/- 19.9 ml 100 g(-1) min(-1), respectively. A significant difference was observed between SCC and IP (p < 0.001), SCC and non-aggressive IP (p < 0.01) and non-aggressive IP and aggressive IP (p < 0.01). The diagnostic accuracy values obtained with receiver operating characteristic curve analysis for the differentiation of SCC from IF and for SCC from non-aggressive IP were 0.90 and 0.92, respectively. The diagnostic accuracy was elevated (0.95 from 0.88) by adding the TBF value to CCP findings.
Conclusions: The pseudocontinuous arterial spin labelling technique can be a useful non-invasive diagnostic tool to differentiate SCC from IP in nasal or sinonasal cavity., BRITISH INST RADIOLOGY, 英語

初期治療に抵抗を示した急性低音障害型感音難聴の検討
森田 真也, 藤原 圭志, 中丸 裕爾, 福田 篤, 福田 諭, Otology Japan, 25, 4, 425, 425, 2015年09月
(一社)日本耳科学会, 日本語

急性感音難聴患者におけるムンプスIgM抗体陽性率の検討
福田 篤, 森田 真也, 藤原 圭志, 中丸 裕爾, 福田 諭, Otology Japan, 25, 4, 426, 426, 2015年09月
(一社)日本耳科学会, 日本語

アレルギー疾患の最新治療 アレルギー性鼻炎に対する舌下免疫治療　　　　　　　　　　　　　　　
中丸 裕爾, 日本臨床皮膚科医会雑誌, 32, 5, 561, 562, 2015年09月
日本臨床皮膚科医会, 日本語

耳鼻咽喉科領域疾患に関与するユビキチン化タンパク質修飾
鈴木 正宣, 渡部 昌, 中丸 裕爾, 高木 大, 加納 里志, 本間 あや, 畠山 鎮次, 福田 諭, 耳鼻咽喉科免疫アレルギー, 33, 3, 185, 192, 2015年09月
ユビキチン化修飾は真核生物に広く存在するタンパク質翻訳後修飾の一つであり,多岐にわたる細胞機能を制御する。ユビキチン化修飾系の異常を原因とする疾患も数多く知られており,耳鼻咽喉科領域においても内耳や鼻粘膜の環境恒常性や,自己免疫・炎症性疾患や悪性疾患の病態に関連していることが報告されている。標的タンパク質へのユビキチンの共有結合は,ユビキチン活性化酵素(E1),ユビキチン連結酵素(E2),ユビキチンリガーゼ(E3)の3つの酵素群が担っている。この中でもE3は基質の特異性を決定する酵素であり,その機能と標的である基質を明らかにすることは,さまざまな疾患の病態解明において重要な課題となっている。耳鼻科領域の疾患において,ユビキチン修飾系についての研究は始まったばかりであり,今後,病態の解明,検査法の確立や新規治療法の開発につながる可能性を秘めている。(著者抄録), 日本耳鼻咽喉科免疫アレルギー学会, 日本語

耳鼻咽喉科における好酸球性多発血管炎性肉芽腫症
中丸 裕爾, 耳鼻咽喉科免疫アレルギー, 33, 3, 205, 207, 2015年09月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

鼻粘膜時計遺伝子発現の概日リズムにグルココルチコイドが影響を及ぼす　　　　　　　　　　　　　　　
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 本間 研一, 本間 さと, 福田 諭, 日本鼻科学会会誌, 54, 3, 376, 376, 2015年09月
(一社)日本鼻科学会, 日本語

アレルギー性鼻炎、鼻副鼻腔炎に続発する好酸球性多発血管炎性肉芽腫症(EGPA)　　　　　　　　　　　　　　　
中丸 裕爾, 耳鼻咽喉科臨床 補冊, 補冊142, 81, 81, 2015年06月
耳鼻咽喉科臨床学会, 日本語

Bechet病疾患感受性遺伝子Tripartite motif protein 39(TRIM39)の機能解析
鈴木 正宣, 渡部 昌, 中丸 裕爾, 高木 大, 本間 あや, 畠山 鎮次, 福田 諭, 耳鼻咽喉科免疫アレルギー, 33, 2, 38, 39, 2015年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

好酸球性副鼻腔炎における術後好酸球数の変動について
高木 大, 本間 あや, 中丸 裕爾, 鈴木 正宣, 福田 諭, 耳鼻咽喉科免疫アレルギー, 33, 2, 50, 51, 2015年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

北海道上士幌町におけるアレルギー性疾患の疫学調査
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 今野 哲, 福田 諭, 耳鼻咽喉科免疫アレルギー, 33, 2, 128, 129, 2015年06月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

【これからのアレルギー性鼻炎対策】 アレルギー性鼻炎の手術療法　　　　　　　　　　　　　　　
中丸 裕爾, ENTONI, 180, 25, 30, 2015年05月
アレルギー性鼻炎の罹患率は依然として増加の一途をたどっている。抗原を回避したうえでの薬物療法が治療の中心となっているが、治療を受けた患者の満足度は高くない。様々な治療を試みても症状をコントロールできない患者、特に薬物療法に反応しづらい鼻閉を主な症状とする患者には手術治療が適応となる。手術療法には(1)レーザー治療やトリクロール酢酸塗布などの鼻粘膜の縮小と変調を目的としたもの、(2)粘膜下下鼻甲介切除や下鼻甲介粘膜切除などの鼻閉の改善を目的とした手術、(3)後鼻神経切断術やvidian神経切断術などの鼻漏の改善を目的とした手術がある。それぞれの手術法で高い効果が報告されているが、2重盲検試験が不足しており本当の効果は不明である。また術後に鼻粘膜の機能が障害され後鼻漏や鼻の乾燥症状が持続するいわゆる"Empty Nose"が生じることがあるため、適応を十分評価してからの施行が望まれる。(著者抄録), (株)全日本病院出版会, 日本語

アレルギー疾患の最新治療 アレルギー性鼻炎の最新治療　　　　　　　　　　　　　　　
中丸 裕爾, 日本臨床皮膚科医会雑誌, 32, 3, 324, 324, 2015年05月
日本臨床皮膚科医会, 日本語

非都市部におけるアレルギー性疾患の実態 北海道上士幌町民を対象としたアンケートによる疫学調査
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 今野 哲, 福田 諭, 日本耳鼻咽喉科学会会報, 118, 4, 540, 540, 2015年04月
(一社)日本耳鼻咽喉科学会, 日本語

成人喘息病態 喘息患者における副鼻腔CT所見とその関連因子　　　　　　　　　　　　　　　
木村 孔一, 今野 哲, 中丸 裕爾, 牧田 比呂仁, 谷口 菜津子, 清水 薫子, 鈴木 雅, 西村 正治, アレルギー, 64, 3-4, 468, 468, 2015年04月
(一社)日本アレルギー学会, 日本語

好酸球性副鼻腔炎における術後好酸球数の変動
高木 大, 中丸 裕爾, 本間 あや, 鈴木 正宣, 福田 諭, アレルギー, 64, 3-4, 561, 561, 2015年04月
(一社)日本アレルギー学会, 日本語

Sinus Computed Tomographic Findings In Asthmatics: Comparison Between Mild-To-Moderate And Severe Asthma And Associations With Asthma-Related Indices
H. Kimura, S. Konno, Y. Nakamaru, H. Makita, N. Taniguchi, K. Shimizu, M. Suzuki, M. Nishimura, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 191, 2015年
AMER THORACIC SOC, 英語, 研究発表ペーパー・要旨（国際会議）

耳鼻咽喉科領域疾患に関与するユビキチン化タンパク質修飾
鈴木正宣, 鈴木正宣, 渡部昌, 中丸裕爾, 高木大, 加納里志, 本間あや, 畠山鎮次, 福田諭, 耳鼻咽喉科免疫アレルギー(Web), 33, 3, 185-192 (J-STAGE), 2015年
日本語

ベーチェット病感受性遺伝子Tripartite motif protein 39(TRIM39)の機能解析
鈴木正宣, 鈴木正宣, 渡部昌, 中丸裕爾, 高木大, 本間あや, 畠山鎮次, 福田諭, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 33rd, 82, 2015年
日本語

各科における血管病の診療と研究 耳鼻咽喉科医が診るANCA関連血管炎　　　　　　　　　　　　　　　
中丸 裕爾, 高木 大, 福田 諭, 脈管学, 54, 12, 212, 212, 2014年12月
(一社)日本脈管学会, 日本語

耳鳴に対するエスシタロプラムの有効性　　　　　　　　　　　　　　　
桝谷 将偉, 中丸 裕爾, 森田 真也, 福田 諭, 耳鼻咽喉科・頭頸部外科, 86, 12, 1047, 1050, 2014年11月
耳鳴りに対する3ヵ月以上の内服治療で効果がなかった症例32例(男性23例、女性9例)を対象に、エスシタロプラム使用の有効性・安全性について検討した。対象のうち内服の継続が可能であった23例を評価対象とした。耳鳴りはTHIスコアで評価し、平均値は投与前41.3±25.9、8週目29.2±20.6、10週目29.1±20.4で、投与後8週目と10週目で有意な改善を認めた。8週目でスコアが低下したのは19例(82%)で、軽症(18〜36点)以下で11例中9例、中等症(38〜56点)で5例中3例、重症(59〜100点)で5例中5例、最重症で2例中2例であった。うち有意改善は9例(39%)で、軽症以下で2例、中等症で3例、重症で3例、最重症で1例であった。有害事象は参加症例32例中14例で認め、うち9例は内服中断後に症状は速やかに消失した。以上より、エスシタロプラムはTHIスコア中等症以上の耳鳴りに有効であることが示唆された。, (株)医学書院, 日本語

アレルギー性鼻炎に対する舌下免疫療法　　　　　　　　　　　　　　　
中丸 裕爾, 北海道医学雑誌, 89, 2, 156, 156, 2014年11月
北海道医学会, 日本語

【こんなときどうする】 鼻科学領域 鼻副鼻腔乳頭腫の基部と進展範囲がはっきりしない!　　　　　　　　　　　　　　　
中丸 裕爾, JOHNS, 30, 9, 1212, 1213, 2014年09月
(株)東京医学社, 日本語

経口ステロイド内服と鼓膜チューブ留置により治療した中耳コレステリン肉芽腫の2例　　　　　　　　　　　　　　　
桝谷 将偉, 中丸 裕爾, 森田 真也, 福田 諭, Otology Japan, 24, 4, 381, 381, 2014年09月
(一社)日本耳科学会, 日本語

早期外耳道癌症例における治療前後の聴力に関する検討　　　　　　　　　　　　　　　
森田 真也, 中丸 裕爾, 桝谷 将偉, 福田 諭, Otology Japan, 24, 4, 623, 623, 2014年09月
(一社)日本耳科学会, 日本語

好酸球性多発血管炎性肉芽腫症(EGPA)と鼻科領域関連疾患
中丸 裕爾, 日本鼻科学会会誌, 53, 3, 343, 343, 2014年09月
(一社)日本鼻科学会, 日本語

非都市部におけるアレルギー性疾患の疫学調査
本間 あや, 中丸 裕爾, 高木 大, 鈴木 正宣, 今野 哲, 福田 諭, 日本鼻科学会会誌, 53, 3, 408, 408, 2014年09月
(一社)日本鼻科学会, 日本語

好酸球性副鼻腔炎における術後好酸球数の変動について　　　　　　　　　　　　　　　
高木 大, 本間 あや, 中丸 裕爾, 鈴木 正宣, 福田 諭, 日本鼻科学会会誌, 53, 3, 418, 418, 2014年09月
(一社)日本鼻科学会, 日本語

耳症状を呈したIgG4関連疾患症例の検討(Otologic manifestations of immunoglobulin G4-related disease)　　　　　　　　　　　　　　　
高木 大, 中丸 裕爾, 福田 諭, 耳鼻咽喉科免疫アレルギー, 32, 2, 82, 83, 2014年07月
日本耳鼻咽喉科免疫アレルギー学会, 英語

アレルギー性鼻炎に対する手術療法と薬物療法　　　　　　　　　　　　　　　
中丸 裕爾, 高木 大, 福田 諭, 耳鼻咽喉科免疫アレルギー, 32, 2, 178, 178, 2014年07月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

ベーチェット病感受性遺伝子Tripartite motif protein39(TRIM39)の機能解析
鈴木正宣, 渡部昌, 高木大, 中丸裕爾, 畠山鎮次, 福田諭, 日本耳鼻咽喉科学会会報, 117, 4, 504, 504, 2014年04月20日
(一社)日本耳鼻咽喉科学会, 日本語

難治性喘息患者における血清ペリオスチン濃度と呼吸機能・副鼻腔陰影重症度との関連
木村孔一, 今野哲, 中丸裕爾, 牧田比呂仁, 谷口菜津子, 清水薫子, 前田由起子, 鈴木雅, 長井桂, 小野純也, 太田昭一郎, 出原賢治, 西村正治, アレルギー, 63, 3/4, 568, 568, 2014年04月05日
(一社)日本アレルギー学会, 日本語

好酸球性副鼻腔炎における術後好酸球数の変動について
高木大, 本間あや, 中丸裕爾, 鈴木正宣, 福田諭, 日本鼻科学会会誌(Web), 53, 3, 2014年

耳症状を合併したIgG4関連疾患についての検討
高木大, 中丸裕爾, 福田諭, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 32nd, 100, 2014年
日本語

MS5-1 IgG4関連疾患における副鼻腔炎の検討(MS5 IgG4関連疾患と膠原病類縁疾患,ミニシンポジウム,第63回日本アレルギー学会秋季学術大会)
高木 大, 中丸 裕爾, 福田 諭, アレルギー, 62, 9, 1287, 1287, 2013年10月25日
一般社団法人日本アレルギー学会, 日本語

MS5-2 ANCA関連血管炎疲候群の耳,鼻症状(MS5 IgG4関連疾患と膠原病類縁疾患,ミニシンポジウム,第63回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 福田 諭, アレルギー, 62, 9, 1287, 1287, 2013年10月25日
一般社団法人日本アレルギー学会, 日本語

副鼻腔炎を合併したIgG4関連疾患症例　　　　　　　　　　　　　　　
高木 大, 中丸 裕爾, 福田 諭, 日本鼻科学会会誌, 52, 3, 407, 407, 2013年09月
(一社)日本鼻科学会, 日本語

好酸球性副鼻腔炎の臨床像の検討
本間あや, 高木大, 中丸裕爾, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 31st, 131, 2013年
日本語

副鼻腔炎を呈したIgG4関連疾患症例
高木大, 中丸裕爾, 鈴木正宣, 本間あや, 福田諭, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 31st, 100, 2013年
日本語

重症喘息患者における副鼻腔陰影の検討
中丸裕爾, 高木大, 本間あや, 福田諭, 谷口菜津子, 今野哲, 牧田比呂仁, 西村正治, 日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集, 31st, 108, 2013年
日本語

副鼻腔炎を合併したIgG4関連疾患症例
高木大, 中丸裕爾, 福田諭, 日本鼻科学会会誌(Web), 52, 3, 407(J-STAGE), 2013年
日本語

診断に苦慮したNK/T細胞リンパ腫の20例
柳 紘子, 中丸 裕爾, 高木 大, 久保田 佳奈子, 福田 諭, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 88, 1, 43, 43, 2013年01月01日
日本語

O7-5 SIRT1蛋白の肥満細胞におけるIL-4産生調節(鼻アレルギー 病態と治療,口演,第62回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 福田 論, アレルギー, 61, 9, 1468, 1468, 2012年10月25日
一般社団法人日本アレルギー学会, 日本語

O74-2 ヒストンアセチル化がWegener肉芽腫症におよぼす影響について(血管炎,口演,第62回日本アレルギー学会秋季学術大会)
高木 大, 中丸 裕爾, 福田 諭, アレルギー, 61, 9, 1566, 1566, 2012年10月25日
一般社団法人日本アレルギー学会, 日本語

通年性アレルギー性鼻炎のエビデンス
中丸 裕爾, 鼻アレルギーフロンティア, 12, 3, 126, 129, 2012年09月
メディカルレビュー社, 日本語

P-197 当科における中枢性嗅覚障害症例に関する検討(ポスターセッション,2011年度日本味と匂学会第45回大会)
打田 武史, 中丸 裕爾, 高木 大, 佐伯 昌彦, 小原 雅子, 福田 諭, 日本味と匂学会誌, 18, 3, 607, 608, 2011年12月
日本味と匂学会, 日本語

WEERDA型拡張式ビデオ喉頭鏡を用いた経口的喉頭・咽頭手術.
折舘伸彦, 本間明宏, 中丸裕爾, 鈴木清護, 福田諭, 耳展, 54, 5, 355, 359, 2011年10月
耳鼻咽喉科展望会, 日本語

内視鏡下に摘出しえた鼻腔神経鞘腫例
洲崎 真吾, 高木 大, 中丸 裕爾, 福田 諭, 耳鼻咽喉科臨床, 104, 3, 181, 185, 2011年
Schwannoma is a neurogenic tumor arising in peripheral nerve sheath Schwann cells. Most head and neck schwannomas occur as acoustic neurinomas, with sinonasal involvement accounting for 3%. Complete resection is vital to preventing local recurrence. Extended resection may be difficult however due to paranasal sinus location. We report a case of sinonasal schwannoma resected in endoscopic sinus surgery and discuss the usefulness of and about indications for intranasal schwannoma treatment., 耳鼻咽喉科臨床学会, 日本語

MW2-2 好酸球性副鼻腔炎手術症例の検討(MW2 副鼻腔炎 診療・研究の進歩,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)
高木 大, 中丸 裕爾, 福田 諭, アレルギー, 59, 9, 1343, 1343, 2010年10月30日
一般社団法人日本アレルギー学会, 日本語

MW2-7 ANCA関連血管炎症候群の耳症状(MW2 副鼻腔炎 診療・研究の進歩,ミニワークショップ,第60回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 福田 諭, アレルギー, 59, 9, 1344, 1344, 2010年10月30日
一般社団法人日本アレルギー学会, 日本語

鼻副鼻腔 inverted papilloma のマネージメント
中丸 裕爾, 日本鼻科学会会誌, 49, 1, 56, 58, 2010年03月01日
日本語

MS11-#1 酸化ストレス下におけるヒストン脱アセチル化酵素とコリプレッサーMi2の役割(気道上皮細胞/線維芽細胞/血管内皮細胞とアレルギー病態2,第59回日本アレルギー学会秋季学術大会)
高木 大, 中丸 裕爾, 福田 諭, アレルギー, 58, 8, 1231, 1231, 2009年09月30日
一般社団法人日本アレルギー学会, 日本語

MS42-#1 肥満細胞におけるSIRT1によるIL-4産生調節(マスト細胞・好塩基球とアレルギー病態2,第59回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 福田 諭, アレルギー, 58, 8, 1331, 1331, 2009年09月30日
一般社団法人日本アレルギー学会, 日本語

小児通年性アレルギー性鼻炎に対する舌下免疫療法の臨床効果の検討　　　　　　　　　　　　　　　
米倉 修二, 有本 昇平, 桜井 大樹, 堀口 茂俊, 花澤 豊行, 岡本 美孝, 仲野 敦子, 有本 友季子, 厳 瑩, 工藤 典代, 中丸 裕爾, 本田 耕平, 耳鼻咽喉科免疫アレルギー, 27, 2, 210, 211, 2009年09月
日本耳鼻咽喉科免疫アレルギー学会, 日本語

難聴遺伝子診断が有用であった人工内耳一症例
武市 紀人, 柏村 正明, 中丸 裕爾, 津布久 崇, 福田 諭, 鈴木 美華, 宇佐美 真一, Audiology Japan, 52, 4, 214, 219, 2009年08月31日
日本語

175 酸化ストレス下におけるヒストン脱アセチル化酵素とコリプレッサーの役割(気道上皮細胞・組織構成細胞,一般演題,第21回日本アレルギー学会春季臨床大会)
高木 大, 中丸 裕爾, 福田 諭, アレルギー, 58, 3, 432, 432, 2009年04月30日
一般社団法人日本アレルギー学会, 日本語

小児アレルギーの病態と治療 小児アレルギー疾患に対するハウスダストエキスを用いた舌下免疫療法の検討 二重盲検試験より　　　　　　　　　　　　　　　
米倉 修二, 櫻井 大樹, 堀口 茂俊, 花澤 豊行, 岡本 美孝, 仲野 敦子, 有本 友季子, 厳 瑩, 吉江 うらら, 工藤 典代, 中丸 裕爾, 本田 耕平, アレルギー, 58, 3-4, 376, 376, 2009年04月
(一社)日本アレルギー学会, 日本語

SIRT1による肥満細胞のIL-4産生調節
中丸 裕爾, 高木 大, 前田 昌紀, 福田 諭, 耳鼻咽喉科免疫アレルギー, 27, 2, 80, 81, 2009年02月12日
日本語

鼻腔病変を有するIgG4関連疾患症例の検討
水町 貴諭, 中丸 裕爾, 前田 昌紀, 高木 大, 福田 諭, 耳鼻咽喉科免疫アレルギー, 27, 2, 159, 160, 2009年02月12日
日本語

マイクロデブリッダーが有用であった成人型多発性喉頭乳頭腫の一例
鈴木正宣, 鈴木正宣, 折舘伸彦, 本間明宏, 中丸裕爾, 畠山博充, 目須田康, 古田康, 古田康, 福田諭, 日本頭頸部外科学会総会ならびに学術講演会プログラム・予稿集, 19th, 2009年

鼻副鼻腔内反性乳頭腫手術における上顎洞前壁の処理 ーマイクロドリルを用いた対側鼻腔からのアプローチ方法ー
中丸 裕爾, 原 敏浩, 水町 貴諭, 福田 諭, 古田 康, 耳展, 52, 5, 386, 388, 2009年

当科における耳科領域疾患のナビゲーション手術の評価
武市 紀人, 中丸 裕爾, 柏村 正明, 古田 康, 福田 諭, 耳展, 52, 5, 376, 379, 2009年

MS2-6 肥満細胞におけるヒストン脱アセチル化酵素によるIL-4産生調節(マスト細胞・好塩基球,第58回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 福田 諭, アレルギー, 57, 9, 1394, 1394, 2008年10月30日
一般社団法人日本アレルギー学会, 日本語

小児通年性アレルギー性鼻炎に対する舌下免疫療法の臨床効果の検討　　　　　　　　　　　　　　　
米倉 修二, 吉江 うらら, 桜井 大樹, 堀口 茂俊, 花澤 豊行, 岡本 美孝, 仲野 敦子, 有本 有季子, 厳 瑩, 工藤 典代, 中丸 裕爾, 本田 耕平, 日本鼻科学会会誌, 47, 3, 231, 231, 2008年08月
(一社)日本鼻科学会, 日本語

P150 耳鼻咽喉科領域におけるIgG4関連硬化性疾患(自己免疫疾患2,第20回日本アレルギー学会春季臨床大会)
前田 昌紀, 中丸 裕爾, 高木 大, 福田 諭, アレルギー, 57, 3, 418, 418, 2008年04月30日
一般社団法人日本アレルギー学会, 日本語

耳鼻咽喉科アレルギー研究・診療施設紹介 北海道大学大学院医学研究科 耳鼻咽喉科・頭頸部外科学教室
中丸 裕爾, 福田 諭, 鼻アレルギーフロンティア, 8, 1, 50, 54, 2008年01月
メディカルレビュー社, 日本語

病診・診診連携 シラカバ花粉症
中丸 裕爾, 鼻アレルギーフロンティア, 8, 1, 46, 49, 2008年01月
メディカルレビュー社, 日本語

318 IL-21処理樹状細胞によって刺激されたNKT細胞のIFN-γ産生増強効果(自然免疫,一般演題(デジタルポスター),第57回日本アレルギー学会秋季学術大会)
前田 昌紀, 高木 大, 中丸 裕爾, 小野江 和則, 福田 論, アレルギー, 56, 8, 1156, 1156, 2007年09月30日
一般社団法人日本アレルギー学会, 日本語

346 ヒストン脱アセチル化酵素による肥満細胞におけるIL-4産生調節(肥満細胞,好塩基球4,一般演題(デジタルポスター),第57回日本アレルギー学会秋季学術大会)
中丸 裕爾, 高木 大, 前田 昌紀, 福田 論, アレルギー, 56, 8, 1163, 1163, 2007年09月30日
一般社団法人日本アレルギー学会, 日本語

アレルギー性鼻炎におけるマクロファージ遊走阻止因子の役割
中丸 裕爾, 高木 大, 前田 昌紀, 間口 四郎, 小野寺 伸, 福田 諭, 日本鼻科学会会誌, 46, 1, 32, 34, 2007年04月01日
日本語

Oxidative stress regulates IL-4 gene expression in mast cells through reduction of histone deacetylase (HDAC)
Y. Nakamaru, D. Takagi, M. Maeda, P. J. Barnes, S. Fukuda, K. Ito, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 119, 1, S138, S138, 2007年01月
MOSBY-ELSEVIER, 英語, 研究発表ペーパー・要旨（国際会議）

当科外来における Oral Allergy Syndrome の検討
前田 昌紀, 中丸 裕爾, 福田 諭, 口腔・咽頭科 = Stomato-pharyngology, 19, 1, 42, 42, 2006年08月10日
日本語

401 関節炎モデルにおけるマクロファージ遊走阻止因子およびNKT細胞の役割(膠原病と類縁疾患(6), 第55回日本アレルギー学会秋季学術大会)
高木 大, 中丸 裕爾, 前田 昌紀, 福田 諭, 小野江 和則, アレルギー, 54, 8, 1107, 1107, 2005年09月30日
一般社団法人日本アレルギー学会, 日本語

496 Wegener肉芽腫症および反復性多発性軟骨炎におけるVa24+Vb11+NKT細胞の機能異常
高木 大, 中丸 裕爾, 間口 四郎, 前田 昌紀, 福田 諭, 小野江 和則, アレルギー, 53, 8, 1004, 1004, 2004年09月30日
一般社団法人日本アレルギー学会, 日本語

鼻副鼻腔乳頭腫の画像診断とそれに基づく手術法の選択
古田 康, 及川 敬太, 中丸 裕爾, 福田 諭, 日本鼻科学会会誌, 43, 1, 116, 118, 2004年04月01日
日本語

側頭骨手術における光学式ナビゲーションシステムの使用経験(第4報)
福田 諭, 千田 英二, 佐伯 昌彦, 中丸 裕爾, 松村 道哉, 柏村 正明, 古田 康, Otology Japan, 13, 4, 389, 389, 2003年09月12日
日本語

側頭骨に発生した好酸球肉芽腫症4例の検討
松村 道哉, 柏村 正明, 千田 英二, 中丸 裕爾, 福田 諭, Otology Japan, 13, 4, 537, 537, 2003年09月12日
日本語

Open cavity 耳における聴力の長期変化の検討
柏村 正明, 千田 英二, 松村 道哉, 中丸 裕爾, 福田 諭, Otology Japan, 13, 4, 405, 405, 2003年09月12日
日本語

MPO-ANCA陽性両側進行性難聴の臨床像
高木 大, 中丸 裕爾, 間口 四郎, 前田 昌紀, 福田 諭, 耳鼻咽喉科免疫アレルギー, 21, 2, 124, 125, 2003年06月30日
日本語

鼻アレルギー炎症局所におけるマクロファージ遊走阻止因子の発現
中丸 裕爾, 高木 大, 前田 昌紀, 古田 康, 福田 論, 間口 四郎, 耳鼻咽喉科免疫アレルギー, 21, 2, 16, 17, 2003年06月30日
日本語

Relapsing Polychondritis (反復性多発性軟骨炎) の内耳障害
前田 昌紀, 中丸 裕爾, 高木 大, 間口 四郎, 福田 諭, 耳鼻咽喉科免疫アレルギー, 21, 2, 132, 133, 2003年06月30日
日本語

アレルギー性鼻炎患者におけるマクロファージ遊走阻止因子
中丸 裕爾, 高木 大, 福田 諭, 間口 四郎, アレルギー, 52, 2, 309, 309, 2003年03月30日
一般社団法人日本アレルギー学会, 日本語

MPO-ANCA陽性両側進行性難聴の臨床像
高木 大, 中丸 裕爾, 福田 諭, 間口 四郎, アレルギー, 52, 2, 379, 379, 2003年03月30日
一般社団法人日本アレルギー学会, 日本語

側頭骨手術における光学式ナビゲーションシステムの使用経験(第3報)
福田 諭, 千田 英二, 佐伯 昌彦, 中丸 裕爾, 黒田 努, 松村 道哉, 武市 紀人, 古田 康, Otology Japan, 12, 4, 231, 231, 2002年09月12日
日本語

外耳・中耳感染症に対するBurow's solutionの効果と安全性について
柏村 正明, 寺山 吉彦, 千田 英二, 中丸 裕爾, 松村 道哉, 福田 論, Otology Japan, 12, 4, 412, 412, 2002年09月12日
日本語

ウェゲナー肉芽腫症におけるc-ANCA(IIF)の有用性
高木 大, 中丸 裕爾, 間口 四郎, 福田 諭, 耳鼻咽喉科免疫アレルギー, 20, 2, 74, 75, 2002年06月30日
日本語

鼻アレルギー患者におけるマクロファージ遊走阻止因子
中丸 裕爾, 折舘 伸彦, 高木 大, 前田 昌紀, 古田 康, 福田 諭, 間口 四郎, 耳鼻咽喉科免疫アレルギー, 20, 2, 108, 109, 2002年06月30日
日本語

194 当科におけるrelapsing polychondritisの治療経験
中丸 裕爾, 高木 大, 福田 諭, 間口 四郎, アレルギー, 51, 2, 291, 291, 2002年03月01日
一般社団法人日本アレルギー学会, 日本語

195 ウェゲナー肉芽腫症の耳症状
高木 大, 中丸 裕爾, 間口 四郎, 福田 諭, アレルギー, 51, 2, 291, 291, 2002年03月01日
一般社団法人日本アレルギー学会, 日本語

ウェゲナー肉芽腫症の耳症状
高木 大, 福田 諭, 中丸 裕爾, 千田 英二, 松村 直哉, 間口 四郎, Otology Japan, 11, 4, 361, 361, 2001年09月12日
日本語

側頭骨手術における光学式ナビゲーションシステムの使用経験(第2報)
福田 諭, 佐伯 昌彦, 千田 英二, 中丸 裕爾, 黒田 努, 松村 道哉, 武市 紀人, 古田 康, Otology Japan, 11, 4, 312, 312, 2001年09月12日
日本語

当科における relapsing polychondritis の治療経験
中丸 裕爾, 福田 諭, 間口 四郎, 犬山 征夫, 耳鼻咽喉科免疫アレルギー, 19, 2, 194, 195, 2001年06月30日
日本語

難治性口腔咽頭潰瘍の臨床的検討
高木 大, 福田 諭, 中丸 裕爾, 犬山 征夫, 間口 四郎, 耳鼻咽喉科免疫アレルギー, 19, 2, 186, 187, 2001年06月30日
日本語

釧路地方におけるアレルギー性鼻炎症例の臨床的検討
高木 大, 福田 諭, 中丸 裕爾, 犬山 征夫, 間口 四郎, 飯塚 桂司, 日本耳鼻咽喉科學會會報, 104, 6, 675, 681, 2001年06月20日
A clinical study of 107 patients with nasal allergies who were treated at Kushiro General Hospital between April 1998 and March 2000 was performed. Radioallergosorbent tests (RAST), X-rays, and nasal smears for the detection of eosinophilia were performed to obtain a diagnosis of nasal allergy. The patients (50 males, 57 females) ranged in age from 3 to 71 years. The RAST was positive for timothy in 22.4% of the patients, 14.0% for birch and 12.1% for mugwort. The most common pollinosis allergen in the Kushiro area was grass pollen. Other pollinosis allergens were birch pollen and mugwort pollen. We measured the daily count of dispersed birch pollen and timothy pollen in Kushiro and Sapporo. Birch pollen and timothy pollen was dispersed earlier in Kushiro than in Sapporo. Nasal allergies in the Kushiro area appear to be related to local characteristics, such as climate and geographical features., 一般社団法人 日本耳鼻咽喉科学会, 日本語

Relapsing polychondritis: a report of eight eases
Y Nakamaru, S Fukuda, S Maguchi, T Ryu, Y Inuyama, AURIS NASUS LARYNX, 28, S107, S110, 2001年05月
Objective: To investigate clinical manifestations of relapsing polychondritis and to clarify the significance of type II collagen antibody in the disease. Methods: Clinical manifestations and antibody titers were examined in eight cases of relapsing polychondritis which had been treated at Otolaryngology Department, Hokkaido University during the eight years from 1991 to 1998. Anti-type II collagen antibody titer was measured by ELISA method. Results: The most frequent symptom was auricular chondritis; it was seen in 88% (7/8) of the cases. Ocular symptom, nasal chondritis, arthritis, respiratory tract chondritis, and audio-vestibular symptom were also common in the cases. Compared with previous reports, no difference was recognized in the manifestation frequency. Considering none of the samples from the controls was positive for anti-type II collagen antibody, two samples from the disease group were positive. The antibody positive rate was 25% (2/8). Conclusion: Though the measurement of type II collagen antibody titer is not a decisive factor for detection of relapsing polychondritis, it is useful as one of the complementary factors for the diagnosis, since there is no specific test for this disease. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved., ELSEVIER SCI LTD, 英語, その他

Serum level of macrophage migration inhibitory factor as a useful parameter of clinical course in patients with Wegener’s granulomatosis and relapsing polychondritis
Ohwatari, R, Fukuda, S, Iwabuchi, K, Mizue, Y, Nakamaru, Y, Maguchi, S, Inuyama, T, Onoé, K, Nishihira, J, Ann. Oto. Rhino. Laryn., 110, 11, 1035, 1040, 2001年

側頭骨手術における光学式ナビゲーションシステムの使用経験
福田 諭, 千田 英二, 中丸 裕爾, 黒田 努, 佐伯 昌彦, 古田 康, 犬山 征夫, Otology Japan, 10, 4, 491, 491, 2000年09月20日
日本語

イチイ花粉症について
間口 四郎, 後藤田 裕之, 高木 大, 中丸 裕爾, 福田 諭, 耳鼻咽喉科免疫アレルギー, 18, 2, 80, 81, 2000年06月20日
日本語

MPO-ANCA陽性を示した感音難聴の2症例
中丸 裕爾, 福田 諭, 高木 大, 犬山 征夫, 間口 四郎, 耳鼻咽喉科免疫アレルギー, 18, 2, 58, 59, 2000年06月20日
日本語

釧路地方における鼻アレルギーの検討
高木 大, 中丸 裕爾, 福田 諭, 犬山 征夫, 飯塚 桂司, 間口 四郎, 耳鼻咽喉科免疫アレルギー, 18, 2, 78, 79, 2000年06月20日
日本語

反復性多発性軟骨炎症例の検討
中丸 裕爾, 福田 諭, 犬山 征夫, 間口 四郎, 劉 沢周, 耳鼻咽喉科免疫アレルギー, 17, 2, 206, 207, 1999年08月30日
日本語

HTLV-I LTR-env-pXトランスジェニックラットに認められる自己免疫疾患の発症機序の解析　　　　　　　　　　　　　　　
富居 一範, 池田 仁, 菅谷 壽晃, 石津 明洋, 中丸 裕爾, 菊地 和徳, 田中 敏, 脇坂 明美, 吉木 敬, 山崎 英俊, 北海道医学雑誌, 73, 5, 531, 531, 1998年09月
北海道医学会, 日本語

自己免疫疾患発症モデルHTLV-I LTR-env-pXラットにおける血管炎発症機序に関する検討 (厚生省S)
菅谷寿晃, 池田仁, 富居一範, 石津明洋, 中丸裕爾, 山崎英俊, 脇坂明美, 小池隆夫, 吉木敬, 免疫疾患調査研究班難治性血管炎分科会 平成9年度研究報告書, 1998年

種々の膠原病を発症するHTLV-I env-pX遺伝子導入ラットの免疫学的解析
中丸 裕爾, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 72, 5, 529, 544, 1997年09月01日
日本語

HTLV-ILTR-env-pXトランスジェニックラットの末梢血および炎症局所T細胞に関する検討
菅谷寿晃, 池田仁, 石津明洋, 菊地和徳, 田中敏, 中丸裕爾, 富居一範, 山崎英俊, 吉木敬, 日本免疫学会総会・学術集会記録, 27, 1997年

Interleukin-1 alpha regulates Thy-1 expression on rat vascular endothelial cells
A Ishizu, H Ishikura, Y Nakamaru, K Kikuchi, T Koike, T Yoshiki, MICROVASCULAR RESEARCH, 53, 1, 73, 78, 1997年01月
We recently reported that Thy-1, a surface molecule induced on the rat endothelium, regulates vascular permeability at sites of inflammation. Although the rat inferior vena cava (IVC) did not express Thy-1 in vivo, cultured endothelial cells from the IVC did express Thy-1, thereby suggesting that the expression was acquired during cultivation of the cells in vitro, possibly by autoactivation by cytokine-like substances. Interleukin (IL)-1 alpha but not tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma was detected in culture supernatants of rat endothelial cells (REC) by ELISA. The production of IL-1 alpha by REC was augmented by exogenously added IL-1 alpha, thereby implying the presence of autocrine regulation by IL-1 alpha. The unaltered expression of Thy-1 by exogenously added IL-1 alpha suggests that Thy-1 expression on REC had already been maximally induced by autologous cytokines; the expression of Thy-1 on REC was lowered by inhibiting protein kinase C and by depleting IL-1 alpha activity from culture supernatants. Although cytokine-like regulators, other than IL-1 alpha, TNF-alpha, or IFN-gamma, produced by REC may also modulate the expression of Thy-1, it is at least in part mediated by IL-1 alpha in vitro. Moreover, Thy-1 expression was induced on rat vascular endothelium at the subcutis where recombinant IL-1 alpha was injected. The evidence indicates that IL-1 alpha functions as one regulator responsible for the induction of Thy-1 on REC, in vitro as well as in vivo. (C) 1997 Academic Press., ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 英語

Wegener 肉芽腫症と鼻腔内黄色ブドウ球菌について
間口 四郎, 滝沢 昌彦, 中丸 裕爾, 劉 澤周, 佐藤 信清, 犬山 征夫, 耳鼻咽喉科免疫アレルギー, 14, 2, 28, 29, 1996年08月30日
日本語

Thy-1 induced on rat endothelium regulates vascular permeability at sites of inflammation
A Ishizu, H Ishikura, Y Nakamaru, E Takeuchi, C Kimura, T Koike, T Yoshiki, INTERNATIONAL IMMUNOLOGY, 7, 12, 1939, 1947, 1995年12月
We investigated the role of surface adhesion molecules on endothelial cells in regulating vascular permeability, in vitro and in vivo. Cultured rat endothelial cells (REC) express Thy-1, intercellular adhesion molecule-1 (ICAM-1), CD44 and RT1A. Permeability of albumin across the REC monolayer increased through the interaction of Thy-1 and anti-Thy-1 mAb, but not through ICAM-1 and anti-ICAM-1, CD44 and anti-CD44, and RT1A and anti-RT1A mAb. This anti-Thy-1-effect was completely inhibited when the calmodulin antagonist W-7 and the protein kinase inhibitor H-7 was combined, while the IL-6-mediated increase in REC permeability was blocked by either W-7 or H-7, independently. The anti-Thy-1-mediated permeability increase was additively augmented when IL-6 was admired. These data suggest that intracellular signaling pathways of anti-Thy-1- and IL-6-mediated permeability regulation may be overlapping to some extent but are largely independent. As anti-Thy-1-treatment generated rearrangement of vimentin filaments within REC, alteration of the cytoskeleton distribution may possibly correlate with the regulation of permeability. Although Thy-1-expression on rat vascular endothelium in vivo was not evident, it was induced at sites of Freund's complete adjuvant-induced dermatitis. The administered anti-Thy-1 mAb exclusively located on vascular endothelial surface at the sites of inflammation. Vascular permeability in inflamed skin tissues was significantly augmented when anti-Thy-1 but not anti-ICAM-1, anti-CD44 or anti-RT1A mAb was administered i.v., without affecting populations of inflammatory cells. The collective evidence suggests that Thy-1 induced on rat endothelium is one important regulatory event in vascular permeability at sites of inflammation., OXFORD UNIV PRESS UNITED KINGDOM, 英語

好酸球性副鼻腔炎新規治療開発ためのSIRT1活性化剤の基礎的研究
科学研究費助成事業 基盤研究(C)
2020年04月01日 - 2023年03月31日
中丸 裕爾
好酸球性副鼻腔炎は難治の副鼻腔炎で中高年において発症する。鼻腔粘膜上皮の脆弱化が発症の一因とされているが、詳細は不明である。申請者らは老化の保護因子であるSIRT1蛋白を研究し、COPDなどの加齢に伴い発症する炎症性疾患においてSIRT１蛋白の減少が、疾患の病態を形成することを明らかにしてきた。鼻腔粘膜組織において上皮にSIRT1が強発現していることを見出したため本研究の着想にいたった。
本年度までに、①好酸球性副鼻腔炎炎症局所におけるSIRT1発現、②SIRT1による鼻粘膜上皮バリア機能の変化を評価した。
まず好酸球性副鼻腔炎炎症局所のSIRT1の発現を免疫組織化学染色で確認した。1. 手術時に摘出した好酸球性副鼻腔炎患者鈎状突起粘膜および鼻茸組織および対照として肥厚性鼻炎にて手術した下鼻甲介粘膜より凍結切片を作成。2. 抗SIRT1抗体を用い、切片を染色。ABC法にて発色して観察。3. 好酸球性副鼻腔炎炎症局所におけるSIRT1の局在を検討した。結果、下鼻甲介粘膜におけるSIRT1の発現は、上皮細胞に多く認められた。特に上皮の基底層に強い発現を認めた。
次に上皮バリア機能を検討するために、鼻腔粘膜上皮の経上皮バリア機能におけるSIRT1の役割を検討した。手術時に摘出した下甲介粘膜より鼻腔上皮細胞を単離し、Transwell上層に散布し、Air Liquid Interface（ALI）法で培養した。21日培養後、SIRT1の抑制剤(resveratrol)あるいは促進剤(splitomicin)を添加し経上皮電気抵抗を測定した。Covid19パンデミックのため手術が減少しており患者数が集まらず現在検討中である。
日本学術振興会, 基盤研究(C), 北海道大学, 20K09703

好酸球性副鼻腔炎におけるNKT細胞の役割と新しい治療戦略
科学研究費助成事業 基盤研究(C)
2014年04月01日 - 2017年03月31日
高木 大, 中丸 裕爾
好酸球性副鼻腔炎患者の末梢血から単核球を採取して、NKT細胞との関連を検討するため、好酸球性副鼻腔炎患者および非好酸球性副鼻腔炎患者のHDAC活性を測定し、検討した。その結果、好酸球性副鼻腔炎患者群において、HDAC活性は非好酸球性副鼻腔炎患者群に比し有意な低下が認められた。また、好酸球性副鼻腔炎患者で治療後改善した症例では、治療後の、HDAC活性も改善が認められた。
さらに好酸球性副鼻腔炎再発群と非再発群を手術前後で検討したところ、再発例においては手術後早期には術前に比し血清IL-5の低下、また血液中の好酸球数の低下が顕著であった。
日本学術振興会, 基盤研究(C), 北海道大学, 26462575

アレルギー性鼻炎の根治を指向したSIRT1活性化剤の基礎的研究
科学研究費補助金(基盤研究(C))
2015年 - 2017年
中丸 裕爾
アレルギー性鼻炎患者におけるTSLP産生にヒストン脱アセチル化酵素がどのように働くか検討するため、ヒト気道上皮細胞株（Beas-2B細胞）を使用した。細胞がコンフルエントになったところで、ヒストン脱アセチル化酵素の抑制剤を添加した。薬剤投与30分後に細胞を刺激するため、ODN2006を最終濃度1μMで添加した。24時間後に細胞を回収しRNAを抽出した。real time PCR法にてTSLPメッセンジャーRNAの産生量の変化を調べた。
以上の実験の結果、ヒストン脱アセチル化酵素抑制剤の濃度依存性にTSLPの産生が増加した。またヒストンアセチル化酵素促進剤の濃度依存性にTSLPの産生が亢進した。
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 15K10775

SIRT1活性化剤によるアレルギー性鼻炎根治に向けた基礎的研究
科学研究費補助金(基盤研究(C))
2012年 - 2014年
中丸 裕爾
本課題の研究として、まずアレルギー性鼻炎患者の下鼻甲介粘膜におけるIL-33の発現量を検討した。コントロール群の下鼻甲介粘膜と比較すると、アレルギー性鼻炎患者の下鼻甲介粘膜においては、IL-33の発現量が有意に亢進していることが、確認できた。さらに同検体を用いて、SIRT1の発現量を比較すると、SIRT1の発現量はアレルギー性鼻炎炎症局所において有意に低下していることが、確認できた。
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 24592574

アレルギー性鼻炎根治を指向したSIRT1蛋白研究の新しい展開
科学研究費補助金(基盤研究(C))
2009年 - 2011年
中丸 裕爾
近年ヒストン蛋白が修飾を受けクロマチンが構造変化することでDNAからの転写が調節されていることが判明してきた。アレルギー性疾患においてもナイーブT細胞からTh2型細胞への分化の本質がクロマチンの構造変化に起因することが示され、発症や炎症の維持に重要な役割を果たす。今回の研究ではヒストン脱アセチル化作用を持つSIRT1蛋白に注目し、肥満細胞のIL-4産生におけるこの蛋白の関与を検討した。実験にはヒト肥満細胞株(HMC-1)を用いた。HMC-1にSIRT1の活性化剤(resveratrol)と阻害剤(splitomysin)を加えカルシウムイオノファー(A23187)とPMAにて刺激した。刺激後、4時間培養後に細胞を回収した。回収した細胞よりmRNAを採取し、Real time PCR法にてIL-4の産生量を検討した。また、カルシウムイオノファーとPMAで細胞刺激し、24時間培養後、培養上清を回収した。ELISA法にてIL-4蛋白濃度を測定した。SIRT1活性化剤(resveratrol)にて処理をすると、IL-4のmRNA量がresveratrolの濃度依存的に減少した。また蛋白レベルでもresveratrolの濃度依存的にIL-4蛋白量が減少した。逆にSIRT1阻害剤(splitomysin)で処理をした細胞では、IL-4のmRNA、蛋白量がsplitomysinの濃度依存的...
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 21592173

ヒストン脱アセチル化酵素活性化剤を用いたアレルギー性鼻炎根治のための基礎的研究
科学研究費補助金(基盤研究(C))
2007年 - 2008年
中丸 裕爾
ラット肥満細胞(RBL-2H3細胞)をDNP特異的IgEと培養し、ヒストン脱アセチル化酵素阻害剤(Tricostatin A : TSA)を加え、NP-KLH(抗原)を反応させ培養後、細胞を回収した。RNAを採取し、逆転写後real time PCRにてTh2型サイトカイン(IL-4, IL-5)mRNA量を測定した。結果であるが、TSAを添加した細胞ではTSAの濃度依存性にIL-4, IL-5ともにmRNAの産生量が増加した。また、抗原刺激後の培養上清中の蛋白をELISA法にて測定すると、TSAによる肥満細胞からのIL-4の産生亢進は蛋白レベルでも確認できた。以上より、ヒストン脱アセチル化酵素はTh2型サイトカイン産生を抑制している可能性が示唆された。次に、ヒト肥満細胞株にてSIRT1の肥満細胞のTh2型サイトカイン産生に関する実験をした。TSAの代わりにSIRT1の抑制剤であるsuraminを添加した。するとsuraminの濃度依存性にIL-4の産生増加が認められた。一方SIRT1の活性化剤であるresveratorolを添加すると抗原刺激にて誘導されたIL-4の産生は抑制された。またSIRT1のsiRNAを肥満細胞に導入して遺伝子をknock downするとIL-4の産生は増加した。以上のことから、SIRT1は肥満細胞にたいしてTh2型サイトカイン産生を抑制する働きをし...
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 19591950

アレルギー性鼻炎治療を目的としたマクロファージ遊走阻止因子の基礎的研究
科学研究費補助金(基盤研究(C))
2005年 - 2006年
中丸 裕爾
アレルギー性鼻炎の病態形成におけるマクロファージ遊走阻止因子(macrophage inhibitory factor ; MIF)の働きを調べるため、MIFの遺伝子ノックアウトマウスを使用しアレルギーモデルマウスを作成し、アレルギー性鼻炎症状、鼻腔粘膜浸潤好酸球数および鼻腔粘膜内サイトカイン濃度を検討した。結果MIFノックアウトマウスではコントロールマウスに比べ、くしゃみの回数、鼻を掻く回数ともに減少していた。鼻粘膜浸潤好酸球数もMIFノックアウトマウスは有意に減少していた。鼻腔粘膜内サイトカインの濃度は、インターロイキン(IL)-2、IL-4、IL-5、tumor necrotizing factor (TNF)-α、インターフェロン(INF)-γを検討した。MIFノックアウトマウスにおいてはTNF-αの鼻腔粘膜内濃度が低いことが判明した。IL-4,IL-5の濃度もコントロールに比べMIFノックアウトマウスでは低い傾向にあったが、有意な差ではなかった。IL-2,INF-γの濃度に差は認められなかった。さらに、MIFがIgE産生にどのように作用するのかを調べるため、MIFノックアウトマウスにおいてアレルギー性鼻炎モデルを作成し、血清IgE濃度を検討した。野生型マウスにくらべOVA特異的IgEは少ない傾向にあったが、有意な差ではなかった。以上の結果よりMIFはアレルギー性鼻炎...
文部科学省, 基盤研究(C), 北海道大学, 研究代表者, 競争的資金, 17591772

ヘルペス性顔面神経麻痺の病態に関する統合的解明
科学研究費補助金(基盤研究(B))
2004年 - 2006年
古田 康, 澤 洋文, 中丸 裕爾
1.顔面神経麻痺症例におけるヘルペスウイルス再活性化動態の解析Hunt症候群、zoster sine herpete (ZSH)、HSV-1 DNA陽性症例におけるウイルス再活性化動態を定量PCR法とペア血清検査にて解析した。その結果、顔面神経麻痺はVZVおよびHSV-1再活性化の早期から消退期まで様々なタイミングで発症することが明らかとなった。2.Bell麻痺症例における遺伝子発現変化DNAマイクロアレイを用いて患者末梢血単核球における遺伝子発現を、麻痺発症時と回復期で比較した。その結果、発症時により多く発現する遺伝子、回復期により多く発現する遺伝子がいくつか検出された。3.非治癒症例におけるヘルペスウイルス再活性化の検討Bell麻痺と臨床的に診断された症例のうち、非治癒例についてウイルス学的検討を行った。その結果、治らないBell麻痺症例においてはVZVおよびHSV-1再活性化例が多くを占めることが明らかとなった。4.HSV-1再活性化はBell麻痺の何%を占めるのか?HSV-1再活性化症例がBell麻痺の何%を占めるのかを抗HSV抗体保有の有無とVZV再活性化(ZSH)の率から推定した。その結果、約60%の症例においてHSV再活性化がBell麻痺発症に関与していることが推定できた。5.ヘルペスウイルス再活性化動態と麻痺発症パターンからみた抗ウイルス療法の考察ウイルス再活...
文部科学省, 基盤研究(B), 北海道大学, 連携研究者, 競争的資金, 16390482

抗マクロファージ遊走阻止因子を用いたアレルギー性鼻炎治療のための基礎的研究
科学研究費補助金(若手研究(B))
2003年 - 2004年
中丸 裕爾
自然免疫と獲得免疫の橋渡しをするサイトカインであるマクロファージ遊走阻止因子(MIF)に着目し、アレルギー性鼻炎における役割について検討を行なった。この研究課題採択以前に、研究代表者はMIFがアレルギー性鼻炎患者の末梢血中で増加し、その血中濃度は患者の臨床症状と同期することを報告していた。この研究課題では次のステップとして、以下2点について明らかにすることを目的とした。1.鼻粘膜浸潤する炎症細胞のなかで、MIFを産生する細胞を同定する。2.MIFの遺伝子ノックアウトマウス(MIF KOマウス)を用いてアレルギー性鼻炎モデルマウスを作成し正常モデルマウスとアレルギー症状、好酸球浸潤、鼻粘膜中のサイトカイン濃度を比較する。1.MIF産生細胞の同定アレルギー性鼻炎患者下甲介粘膜を抗MIF抗体と炎症細胞の表面マーカー(好酸球;EPO,マクロファージ;CD68,T細胞;CD3)の2重染色にて検討した。結果MIF陽性細胞の大部分はEPOも陽性であった。以上よりアレルギー性炎症局所でのMIF産生細胞は好酸球であることが判明した。2.MIF KOマウスにおけるアレルギー性鼻炎モデルの検討MIF KOマウスにおいては野生型マウスに比べアレルギー鼻症状(くしゃみ、鼻を掻く動作)が有意に減少していた。同様に鼻粘膜に浸潤する好酸球数も有意に減少していた。鼻粘膜中のサイトカインの検討ではTNF-αの濃...
文部科学省, 若手研究(B), 北海道大学, 研究代表者, 競争的資金, 15790918