Researcher Profile and Settings

Affiliation

• Faculty of Medicine　Specialized Medicine　Sensory Organ Medicine

Job Title

• Assistant Professor

J-Global ID

• 201801007892670857

Research Areas

• Life sciences / Otorhinolaryngology

Educational Organization

•  Bachelor's degree program　Departments of Medicine, School of Medicine

Association Memberships

• American rhinologic society   日本耳鼻咽喉科臨床学会   日本耳鼻咽喉科免疫アレルギー学会   日本鼻科学会   日本アレルギー学会   日本耳鼻咽喉科学会   

Research Activities

Published Papers

• SlicerPIT: software development and implementation for planning and image-guided therapy in photoimmunotherapy.

  Takayoshi Suzuki, Satoshi Kano, Masanobu Suzuki, Seijiro Hamada, Hiroshi Idogawa, Nayuta Tsushima, Yuichi Ashikaga, Yuki Wakabayashi, Takeshi Soyama, Yasuhiro Hida, Akihiro Homma

  International journal of clinical oncology 2024/04/23 

  BACKGROUND: Photoimmunotherapy is a treatment modality that induces targeted cell death by binding a molecular-targeted drug activated by infrared light to the tumor cells and subsequently illuminating the lesion with infrared light. For deep lesions, a needle catheter is used to puncture the tumor, and an illumination fiber (cylindrical diffuser) is inserted into the catheter lumen for internal illumination. However, it can be challenging to place the cylindrical diffusers in an appropriate position as the deep lesions cannot be often confirmed accurately during surgery. MATERIALS AND METHODS: We have developed "SlicerPIT", a planning simulation software for photoimmunotherapy. SlicerPIT allows users to place the cylindrical diffuser with its illumination range on preoperative images in 2D and 3D and export the planning data to external image-guided surgical navigation systems. We performed seven cycles of photoimmunotherapy with SlicerPIT in three patients with recurrent head and neck cancer. RESULTS: Preoperative planning for photoimmunotherapy was conducted using SlicerPIT, which could be imported into the navigation system. During the operation, we punctured the needle catheters along with the treatment plan on the navigation screen. Subsequently, intraoperative CT imaging was performed and overlaid with the preoperative treatment plan to confirm the alignment of the cylindrical diffusers as planned, followed by infrared light illumination. Postoperative imaging showed necrosis and shrinkage of the entire tumor in all cycles. CONCLUSION: SlicerPIT allows for detailed preoperative treatment planning and accurate puncture. It may be a valuable tool to improve the accuracy of photoimmunotherapy for deep lesions and improve patient outcomes.
• 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 0385-8146 2023/11
• 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 2023/06/17 

  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.
• 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 2023/03/09 

  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 1349-581X 2023
• 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 

  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.
• 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 (一社)日本アレルギー学会 71 (8) 944 - 948 0021-4884 2022/09 

  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)
• 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 2022/08 [Refereed][Not invited]
   

  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.
• The anatomy of the foramina and efferent nerve fibers from the pterygopalatine ganglion in posterolateral nasal wall.

  Kazuhiro Ogi, Rowan Valentine, Masanobu Suzuki, Shigeharu Fujieda, Alkis James Psaltis, Peter-John Wormald

  Laryngoscope investigative otolaryngology 7 (3) 679 - 683 2022/06 [Refereed]
   

  Background: The advance of endoscopic surgery has enabled selective section of the postganglionic nerve branches from pterygopalatine ganglion (PPG) as a modification of the vidian neurectomy. Recent microanatomic studies have suggested that the nasal mucosa is also innervated by multiple efferent rami associated with the sphenopalatine artery (SPA) in the procedure "posterior nasal neurectomy." This anatomic cadaveric study aims to identify all postganglionic nerve fibers in the lateral nasal wall which should inform future surgical procedures aimed at interrupting these nerve fibers. Methods: Two cadaver heads, with a total of three individual sides, were dissected. All neurovascular structures penetrating the vertical plate of palatine bone were carefully identified following meticulous removal of the overlying mucosa layers. The efferent nerve fibers were identified and dissected back to their origin-the PPG or greater palatine nerve. Results: Several foramina with efferent PPG nerves were identified on the vertical plate of the palatine bone and medial pterygoid plate. The superior, middle, and inferior turbinates (IT) were innervated by efferent nerves from the PPG via the anterior region of the SPA. The IT was innervated from nerves originating from behind the SPA through bony foramina. The lateral wall of inferior meatus was innervated by efferent nerves that originated from greater palatine nerve and pharyngeal nerve. Conclusion: This study demonstrated the anatomical positions of the postganglionic nerves that innervate the lateral nasal wall. These nerves are located anterior to the SPA as well as posterior to the SPA, where they penetrate the palatine bone.Level of evidence: NA.
• 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 (一社)日本呼吸器学会 11 (増刊) 143 - 143 2186-5876 2022/04
• 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  2022/03/01 

  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 2022/02
• Schlafen family member 11 indicates favorable prognosis of patients with head and neck cancer following platinum-based chemoradiotherapy.

  Seijiro Hamada, Satoshi Kano, Junko Murai, Takayoshi Suzuki, Nayuta Tsushima, Takatsugu Mizumachi, Masanobu Suzuki, Tsuyoshi Takashima, Daiki Taniyama, Naoya Sakamoto, Yoichiro Fujioka, Yusuke Ohba, Akihiro Homma

  Frontiers in oncology 12 978875 - 978875 2022 

  Recently, Schlafen family member 11 (SLFN11) has been reported to increase the sensitivity of cancer cells to DNA-damaging agents, including platinum derivatives; thus, SLFN11 may be a predictive biomarker for platinum-based chemoradiotherapy (CRT). In this study, we examined whether SLFN11 expression was associated with the therapeutic outcome of platinum-based CRT in head and neck squamous cell carcinoma (HNSCC). We performed immunohistochemical analyses for SLFN11 expression in 161 HNSCC tissues from patients who had been administered cisplatin-based CRT and examined the correlation between SLFN11 expression and progression-free survival (PFS). Additionally, SLFN11 expression was examined in 10 paired samples obtained before and after CRT in patients with local failure. Furthermore, in vitro experiments were performed using several HNSCC cell lines and isogenic SLFN11-knockout cells to assess the association between SLFN11 expression and drug sensitivity. PFS was found to be significantly better in the SLFN11-positive group than in the SLFN11-negative group among the 161 patients (5-year PFS: 78.8% vs. 52.8%, respectively, p < 0.001). Similar results were observed for the PFS at each primary site. The percentage of SLFN11 positivity was lower in tumor samples from patients with local failure after CRT than that in the corresponding primary tumors before CRT in 8 of 10 cases. Results of the in vitro assay demonstrated that SLFN11-knockout cells exhibited reduced sensitivity to DNA-damaging agents but not to the non-DNA-damaging agent docetaxel. Our findings suggest that SLFN11 may serve as a potential biomarker for predicting the response of HNSCC patients to platinum-based CRT.
• [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 

  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 

  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.
• 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 746837 - 746837 2021/10/01 [Refereed][Not invited]
   

  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 2021/10 [Refereed][Not invited]
   

  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.
• Pediatric allergic fungal rhinosinusitis: optimizing outcomes.

  Masanobu Suzuki, James Connell, Alkis James Psaltis

  Current opinion in otolaryngology & head and neck surgery 29 (6) 510 - 516 2021/09/20 [Refereed][Invited]
   

  PURPOSE OF REVIEW: Allergic fungal rhinosinusitis (AFRS) is a debilitating condition for children. Despite there being several reviews on this topic in the adult population, there is a paucity of reviews of AFRS in the pediatric literature. This article reviews the recent evidence of pediatric AFRS with the aim to optimize outcomes of pediatric patients with this condition. RECENT FINDINGS: AFRS is clinically characterized by nasal polyposis, a type I hypersensitivity to fungal epitopes, very thick eosinophilic mucin, and peripheral eosinophilia. Pediatric AFRS has similar clinical characteristics to that in adults but is thought to have a more aggressive nature, with higher serum immunoglobulin E and more frequently bone erosion and malformation of facial bones. Diagnosis of pediatric AFRS is made by using the Bent and Kuhn's criteria developed for adult AFRS. The mainstay of treatment is surgery followed by postoperative corticosteroids. Adjunctive therapies, including topical/oral antifungal agents, allergen immunotherapy and biologics may improve outcomes in pediatric AFRS, but to date the current evidence is limited. SUMMARY: To optimize the outcome of pediatric AFRS, adequate and early diagnosis and treatment are essential. Appropriate and comprehensive endoscopic sinus surgery to open the sinuses, remove the fungal burden of disease and improve access of the sinuses to postoperative topical corticosteroid remains the standard of care.
• Der p 1 Disrupts the Epithelial Barrier and Induces IL-6 Production in Patients With House Dust Mite Allergic Rhinitis

  Kazuhiro Ogi, Mahnaz Ramezanpour, Sha Liu, Jannatul Ferdoush Tuli, Catherine Bennett, Masanobu Suzuki, Shigeharu Fujieda, Alkis James Psaltis, Peter-John Wormald, Sarah Vreugde

  Frontiers in Allergy 2 692049 - 692049 2021/08/03 [Refereed]
   

  Background:Dermatophagoides pteronyssinus 1/2 (Der p 1/Der p 2) are regarded as important allergens of house dust mite (HDM). However, the effect of both products on the epithelial barrier and immune response of patients with and without HDM allergic rhinitis (AR) remains unclear. Methods: Air–liquid interface (ALI) cultured human nasal epithelial cells (HNECs) derived from control subjects (non-AR) (n = 9) and HDM-AR patients (n = 9) were treated with Der P 1 and Der P 2, followed by testing the transepithelial electrical resistance (TEER), paracellular permeability of fluorescein isothiocyanate (FITC)-dextrans and immunofluorescence of claudin-1 and ZO-1. Interleukin-6 (IL-6) production was evaluated by ELISA. Results: Der p 1 reduced TEER significantly in a transient and dose-dependent manner in HNEC-ALI cultures from HDM-AR and non-AR patients, whilst the paracellular permeability was not affected. TEER was significantly reduced by Der p 1 at the 10-min time point in HDM-AR patients compared to non-AR patients (p = 0.0259). Compared to no-treatment control, in HNECs derived from HDM-AR patients, Der p 1 significantly cleaved claudin-1 after 30 min exposure (72.7 ± 9.5 % in non-AR group, 39.9 ± 7.1 % in HDM-AR group, p = 0.0286) and induced IL-6 secretion (p = 0.0271). Conclusions: Our results suggest that patients with HDM-AR are more sensitive to Der p 1 than non-AR patients with increased effects of Der p1 on the mucosal barrier and induction of inflammation, indicating an important role for Der p1 in sensitization and HDM-AR development.
• 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 2021/07 [Refereed]
  
• 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 (一社)日本アレルギー学会 70 (4) 315 - 320 0021-4884 2021/06
• 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 2021/05/06 [Refereed][Not invited]
   

  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.
• 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 2021/04 [Refereed]
   

  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.
• 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 2021/02 [Refereed]
   

  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.
• 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 

  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.
• Similarity and difference between eosinophilic chronic rhinosinusitis and other type-2 diseases of the nasal cavity and paranasal sinuses

  鈴木正宣, 中丸裕爾

  耳鼻咽喉科・頭頚部外科 (株)医学書院 93 (1) 18 - 23 0914-3491 2021 [Refereed]
   

  ＜文献概要＞POINT ▼好酸球性副鼻腔炎のほかにも,好酸球性多発血管炎性肉芽腫症(EGPA)やIgG4関連疾患など鼻粘膜にTh2優位の炎症(type 2炎症)が存在する病態では,鼻ポリープを生じることがある。▼本邦では早くからtype 2炎症や好酸球浸潤に注目した診療が行われていたが,ヨーロッパ鼻科学会のPosition Paperでも,このtype 2炎症の有無に注目した分類を提唱するようになった。▼近年,central compartment atopic disease(CCAD)という疾患概念が提唱された。呼吸上皮腺腫様過誤腫(REAH)との合併も報告されている。アレルギー性鼻炎や好酸球性副鼻腔炎との相違を含め,今後症例が蓄積され,疾患概念が整理されることが期待される。
• 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 (株)全日本病院出版会 (254) 62 - 70 1346-2067 2021 [Not refereed]
   

  免疫療法は少量の抗原を体内に継続的に投与し、抗原に対する反応性を低下させる治療法である。耳鼻咽喉科領域では鼻アレルギーに対して古くから行われており、その有効性は確立している。薬物治療や外科手術と異なり、免疫反応そのものを変化させるため、アレルギー性疾患に対し治癒や長期寛解が期待できる唯一の治療方法とされる。Pollen-food allergy syndrome(PFAS)に対しては、カバノキ花粉症に伴うリンゴPFASを対象とした免疫療法が、欧州を中心に検討されている。免疫療法が有効とする報告も数多くみられるが、一方で無効とする報告もあり、有効性には一定の見解が得られていない。近年、リコンビナントタンパク質を用いた分子生物学的検討が進むにつれ、免疫療法で摂取する抗原によって有効性が異なることがわかってきた。本稿では、これまでのPFASに対する免疫療法の報告を概説したうえで、最新の免疫療法と近年の分子生物学的検討についても紹介する。(著者抄録)
• 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 (一社)日本耳鼻咽喉科頭頸部外科学会 124 (4) 596 - 596 0030-6622 2021 [Refereed]
  
• 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 耳鼻咽喉科臨床学会 (157) 80 - 80 0912-1870 2021 [Refereed]
  
• 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 耳鼻咽喉科臨床学会 (157) 128 - 128 0912-1870 2021 [Refereed]
  
• 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 耳鼻咽喉科臨床学会 (157) 81 - 81 0912-1870 2021 [Refereed]
  
• 前頭洞手術の基本

  鈴木正宣

  耳鼻咽喉科臨床 補冊 耳鼻咽喉科臨床学会 (157) 48 - 48 0912-1870 2021 [Refereed]
  
• Granulomatosis with Polyangiitis (GPA) Occurring with Binocular Visual Acuity Impairment

  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 耳鼻咽喉科臨床学会 114 (2) 94 - 95 0032-6313 2021 [Refereed]
  
• Development of a measurment system for nasal endscopic surgey

  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 [Not refereed]
  
• Inferior turbinate shoulder osteotomy in a patient with a narrow nasal cavity

  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 (株)医学書院 93 (6) 471 - 474 0914-3491 2021 [Refereed]
   

  症例は65歳男性で、5年前から他院にてアレルギー性鼻炎、慢性副鼻腔炎に対して保存的治療が行われていたが、鼻閉が改善しないため当科を紹介された。両側の内視鏡下鼻副鼻腔手術IV型、鼻中隔矯正術、粘膜下下鼻甲介骨切除術を施行する方針とした。本症例では鼻腔の横幅が狭く、上記術式だけでは内鼻弁を十分に拡大できないことが予想されたため、下鼻甲介shoulder osteotomyも併施した。まず、下鼻甲介の鼻腔外側壁付着部から下鼻甲介前端にかけて粘膜切開を行った。次に、turbinate bladeを用いて下鼻甲介の粘膜下組織を切除した。下鼻甲介前端の粘膜を剥離して下鼻甲介基板(下鼻甲介肩)の骨を同定し、截除鉗子、ノミ、ツチを用いて切除した。最後に、残存下鼻甲介前端を外側に偏位させ、鼻腔外側壁に4-0バイクリルで縫合した。術後3週間の鼻腔内規鏡険査所見では下鼻甲介が外側に偏位し、内鼻弁は拡大していた。前額断CTでは内鼻弁の横幅が術前8.9mmから術後11.5mmに拡大した。また鼻腔通気度検査(P=100Pa)で測定した鼻腔抵抗は術前0.44Pa/cm3/秒から術後2ヵ月半には0.29Pa/cm3/秒と低下した。鼻閉の自覚症状をスコア化したvisual analogue scaleスコア(鼻が完全に閉塞した状態を100%)では、術前の67.8%から術後2ヵ月半には0%に改善し、自覚的にも鼻閉は消失した。
• 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 2021/01 [Refereed]
  
• 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 [Refereed][Not invited]
   

  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] (一社)日本アレルギー学会 70 (4) 315 - 320 0021-4884 2021 [Refereed]
   

  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.
• A substrate-trapping strategy to find E3 ubiquitin ligase substrates identifies Parkin and TRIM28 targets.

  Masashi Watanabe, Yasushi Saeki, Hidehisa Takahashi, Fumiaki Ohtake, Yukiko Yoshida, Yusuke Kasuga, Takeshi Kondo, Hiroaki Yaguchi, Masanobu Suzuki, Hiroki Ishida, Keiji Tanaka, Shigetsugu Hatakeyama

  Communications biology 3 (1) 592 - 592 2020/10/20 [Refereed]
   

  The identification of true substrates of an E3 ligase is biologically important but biochemically difficult. In recent years, several techniques for identifying substrates have been developed, but these approaches cannot exclude indirect ubiquitination or have other limitations. Here we develop an E3 ligase substrate-trapping strategy by fusing a tandem ubiquitin-binding entity (TUBE) with an anti-ubiquitin remnant antibody to effectively identify ubiquitinated substrates. We apply this method to one of the RBR-type ligases, Parkin, and to one of the RING-type ligases, TRIM28, and identify previously unknown substrates for TRIM28 including cyclin A2 and TFIIB. Furthermore, we find that TRIM28 promotes cyclin A2 ubiquitination and degradation at the G1/S phase and suppresses premature entry into S phase. Taken together, the results indicate that this method is a powerful tool for comprehensively identifying substrates of E3 ligases.
• 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 2020/10/01 

  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.
• 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 2152-6567 2020/07 

  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.
• Sixth Report on the Hands-on Seminar on Basic Research for Clinicians at the 58th Annual Meeting of the Japanese Rhinologic Society

  Hosoya Kei, Kanda Akira, Kawauchi Hideyuki, Okubo Kimihiro, Yun Yasutaka, Suzuki Masanobu, Yamada Takaya, Higasa Koichiro, Usukura Norihiro, Homma Aya, Suzuki Kensuke, Iwai Hiroshi

  Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology) 日本鼻科学会 59 (2) 172 - 178 0910-9153 2020 

  The Japanese Rhinologic Society has held a "Hands-on Seminar on Basic Research for Clinicians" led by the Society since 2014. The purpose of these seminars is to raise the motivation and research skills with regard to basic research, and in turn to encourage interdisciplinary collaboration through research with universities. The sixth seminar was held at the 58th Annual Meeting of the Japanese Rhinologic Society in Tokyo. Four methods were discussed: collecting blood and injecting drugs into mice by video, next-generation sequencing, multiplex assay, and preparation of fresh-frozen sections with Kawamoto's film method. A post-event questionnaire indicated that 93% of the participants were satisfied with the seminar. This suggests that the seminar was effective in introducing the new techniques and promoting a strong community-university partnership.

• 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, 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, 清水伸一, 本間明宏, 青山英史

  頭頸部癌 (一社)日本頭頸部癌学会 46 (2) 188 - 188 1349-5747 2020 [Refereed]
  
• 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 (株)東京医学社 36 (9) 1190 - 1192 0910-6820 2020 [Refereed]
  
• A case of nasal septal perforation closure using unilateral mucosal flap based on the anterior ethmoidal artery

  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 (株)医学書院 92 (9) 757 - 760 0914-3491 2020 [Refereed]
   

  68歳男性。既往として10年前に鼻閉に対し他院で鼻中隔矯正術+下甲介切除術が行われたが、術後より鼻出血を生じるようになった。今回、近医の耳鼻咽喉科にて鼻中隔穿孔を指摘され、当科へ紹介された。初診時、前鼻孔から約20mm後方に直径約15mmの鼻中隔穿孔が認められた。内視鏡下に篩骨動脈を茎とする鼻中隔粘膜弁を用いて鼻中隔穿孔閉鎖術を行った結果、穿孔部は完全閉鎖し、術後1年6ヵ月経過で再穿孔はみられていない。
• Sixth Report on the Hands-on Seminar on Basic Research for Clinicians at the 58th Annual Meeting of the Japanese Rhinologic Society

  細矢慶, 尹泰貴, 鈴木正宣, 山田高也, 日笠幸一郎, 臼倉典宏, 本間あや, 鈴木健介, 岩井大, 神田晃, 川内秀之, 大久保公裕

  日本鼻科学会会誌(Web) 59 (2) 1883-7077 2020 [Refereed]
  
• Total Rhinologistを目指して-アデレードから持ち帰ったA to Z-

  鈴木正宣

  耳鼻咽喉科臨床 補冊 耳鼻咽喉科臨床学会 (155) 60 - 60 0912-1870 2020 [Refereed]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 38th (4) 194 - 195 0913-0691 2020
• 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 日本耳鼻咽喉科免疫アレルギー学会 38th (4) 142 - 143 0913-0691 2020 [Not refereed]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 38th (4) 204 - 205 0913-0691 2020 [Not refereed]
  
• Endoscopic skull base surgery for Olfactory Neuroblastoma

  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 [Not refereed]
  
• [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] (一社)日本アレルギー学会 69 (8) 678 - 682 0021-4884 2020 [Refereed]
   

  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.
• Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma.

  Takayoshi Suzuki, Satoshi Kano, Masanobu Suzuki, Shinichiro Yasukawa, Takatsugu Mizumachi, Nayuta Tsushima, Kanako C Hatanaka, Yutaka Hatanaka, Yoshihiro Matsuno, Akihiro Homma

  Frontiers in oncology 10 603717 - 603717 2020 [Refereed]
   

  Salivary duct carcinoma (SDC) is morphologically similar to breast cancer, with HER2-overexpression reported. With regard to the pattern of disease onset, SDC can arise from de novo or carcinoma ex-pleomorphic adenoma (Ca-ex-PA). Recently, multiple molecular profiles of SDC as well as breast cancer have been reported, with significant differences in HER2 expression between Ca-ex-PA and de novo. We assessed the differences in gene expression between onset classifications. We conducted immunohistochemical analysis and HER2-DISH for 23 patients and classified SDCs into three subtypes as follows: "HER2-positive" (HER2+/any AR), "Luminal-AR" (HER2-/AR+), and "Basal-like" (HER2-/AR-). We assessed the expression levels of 84 functional genes for 19 patients by using a qRT-PCR array. Ten cases were classified as HER2-positive, seven cases as Luminal-AR, and six cases as Basal-like. The gene expression pattern was generally consistent with the corresponding immunostaining classification. The expression levels of VEGFA, ERBB2(HER2), IGF1R, RB1, and XBP1 were higher, while those of SLIT2 and PTEN were lower in Ca-ex-PA than in de novo. The functions of those genes were concentrated in angiogenesis and AKT/PI3K signaling pathway (Fisher's test: p-value = 0.025 and 0.004, respectively). Multiple machine learning methods, OPLS-DA, LASSO, and RandomForest, also show that VEGFA can be a candidate for the characteristic differences between Ca-ex-PA and de novo. In conclusion, the AKT/PI3K signaling pathway leading to angiogenesis was hyper-activated in all SDCs, particularly in those classified into the Ca-ex-PAs. VEGFA was over-expressed significantly in the Ca-ex-PA, which can be a crucial factor in the malignant conversion to SDC.
• 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 (一社)日本鼻科学会 58 (3) 632 - 632 0910-9153 2019/09 [Refereed]
  
• 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 1531-7129 2019/02 [Refereed][Not invited]
   

  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 2152-6567 2019/01 [Refereed]
   

  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.
• 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 (株)東京医学社 35 (11) 1581 - 1584 0910-6820 2019 [Refereed]
  
• 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

  日本耳鼻咽喉科免疫アレルギー学会プログラム・抄録集 日本耳鼻咽喉科免疫アレルギー学会 37th (2) 77 - 78 0913-0691 2019 [Not refereed]
  
• 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) 1883-7077 2019 [Refereed]
  
• 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, 中丸祐爾, MAHNAZ Ramezanpour, 鈴木崇祥, 中薗彬, WORMALD Peter-john, VREUGDE Sarah, 本間明宏

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 122 (4) 649 - 649 0030-6622 2019 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 37th (2) 132 - 133 0913-0691 2019
• 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
• 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) 2185-5900 2019 [Refereed]
  
• マルチプレックスアッセイの基礎と手技

  鈴木正宣, 本間あや, 尹泰貴, 三好宗一郎

  日本鼻科学会会誌(Web) 58 (3) 1883-7077 2019 [Refereed]
  
• Pseudomonas aeruginosa Exoprotein-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity.

  Jian Li, Mahnaz Ramezanpour, Stephanie A Fong, Clare Cooksley, Jae Murphy, Masanobu Suzuki, Alkis J Psaltis, Peter John Wormald, Sarah Vreugde

  Frontiers in cellular and infection microbiology 9 38 - 38 2019 [Refereed][Not invited]
   

  Background: Pseudomonas aeruginosa causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). P. aeruginosa exoproteins contain virulence factors and play important roles in the pathogenicity of P. aeruginosa, however their role in CRS pathophysiology remains unknown. Methods: We isolated P. aeruginosa clinical isolates (CIs) and obtained clinical information from 21 CRS patients. Elastase activity of the CIs was measured at different phases of growth. Primary human nasal epithelial cells (HNECs) were cultured at air-liquid interface (ALI) and challenged with P. aeruginosa exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. Results: 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the in vitro elastase activity of P. aeruginosa CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans (r = 0.95, p = 0.0004) and decreased TEER (r = -0.9333, P < 0.01) after 4 h of challenge. Western blot showed a significant degradation of ZO-1, Occludin and β-actin in relation to the elastase activity of the exoproteins. There was a highly significant correlation between the in vitro elastase activity of P. aeruginosa CIs and CRS disease severity (for log phase, r = 0.5631, p = 0.0097; for stationary phase, r = 0.66, p = 0.0013) assessed by CT imaging of the paranasal sinuses. Conclusion: Our results implicate P. aeruginosa exoproteins as playing a major role in the pathophysiology of P. aeruginosa associated CRS by severely compromising mucosal barrier structure and function.
• Sirtuin-1 Controls Poly (I:C)-Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells.

  Masanobu Suzuki, Mahnaz Ramezanpour, Clare Cooksley, Jian Li, Yuji Nakamaru, Akihiro Homma, Alkis Psaltis, Peter-John Wormald, Sarah Vreugde

  American journal of respiratory cell and molecular biology 59 (4) 500 - 510 2018/10 [Refereed][Not invited]
   

  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.
• 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) 835 - 843 2018/10 [Refereed]
   

  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 (一社)日本鼻科学会 57 (3) 429 - 429 0910-9153 2018/09 [Refereed]
  
• 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 (一社)日本鼻科学会 57 (3) 504 - 504 0910-9153 2018/09 [Refereed]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 36 (2) 118 - 119 0913-0691 2018/06 [Refereed][Not invited]
  
• 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 1 - 9 1437-7772 2018/05/19 [Refereed][Not invited]
   

  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.
• 唾液腺導管癌における免疫染色およびRT-PCR法を用いた分子生物学的プロファイルの検討

  鈴木 崇祥, 加納 里志, 畑中 佳奈子, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 畑中 豊, 松野 吉宏, 本間 明宏

  頭頸部癌 (一社)日本頭頸部癌学会 44 (2) 179 - 179 1349-5747 2018/05 [Refereed][Not invited]
  
• SIRT1 Controls Poly(I:C)-dependent MMP9 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 1044-1549 2018/05 [Refereed][Not invited]
  
• 唾液腺導管癌における遺伝子発現解析および発生様式間の比較検討

  鈴木 崇祥, 加納 里志, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 本間 明宏

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 541 - 541 0030-6622 2018/04 [Not refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 121 (4) 567 - 567 0030-6622 2018/04 [Not refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 121 (4) 539 - 539 0030-6622 2018/04 [Not refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 121 (4) 539 - 539 0030-6622 2018/04 [Refereed]
  
• 唾液腺導管癌における遺伝子発現解析および発生様式間の比較検討

  鈴木 崇祥, 加納 里志, 鈴木 正宣, 安川 真一郎, 中薗 彬, 水町 貴諭, 本間 明宏

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 121 (4) 541 - 541 0030-6622 2018/04 [Refereed]
  
• 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 (一社)日本耳鼻咽喉科学会 121 (4) 567 - 567 0030-6622 2018/04 [Refereed]
  
• 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 1537-4505 2018/04/01 [Refereed][Not invited]
   

  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) 2185-5900 2018 [Refereed]
  
• 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) 1883-7077 2018 [Refereed]
  
• 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) 1883-7077 2018 [Refereed]
  
• 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 (一社)日本鼻科学会 56 (3) 429 - 429 0910-9153 2017/09 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 35 (2) 238 - 239 0913-0691 2017/08 [Refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 120 (4) 557 - 557 0030-6622 2017/04 [Refereed][Not invited]
  
• 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 0022-2151 2016/12 [Refereed][Not invited]
   

  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.
• Time course of downbeat positioning nystagmus in familial hemiplegic migraine type 1 treated with acetazolamide.

  Masanobu Suzuki, Keishi Fujiwara, Takashi Tsubuku, Ichiro Yabe, Hidenao Sasaki, Satoshi Fukuda

  Journal of the neurological sciences 368 206 - 8 2016/09/15 [Refereed]
  
• 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 (一社)日本鼻科学会 55 (3) 468 - 468 0910-9153 2016/09 [Refereed][Not invited]
  
• 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 0962-1105 2016/09 [Refereed][Not invited]
  
• 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 (一社)日本鼻科学会 55 (3) 468 - 468 0910-9153 2016/09 [Refereed][Not invited]
  
• Time course of downbeat positioning nystagmus in familial hemiplegic migraine type 1 treated with acetazolamide

  Masanobu Suzuki, Keishi Fujiwara, Takashi Tsubuku, Ichiro Yabe, Hidenao Sasaki, Satoshi Fukuda

  JOURNAL OF THE NEUROLOGICAL SCIENCES 368 206 - 208 0022-510X 2016/09 [Refereed][Not invited]
  
• p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex

  Delnur Anwar, Hidehisa Takahashi, Masashi Watanabe, Masanobu Suzuki, Satoshi Fukuda, Shigetsugu Hatakeyama

  BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 1859 (8) 975 - 982 1874-9399 2016/08 [Refereed][Not invited]
   

  The regulation of transcription by RNA polymerase II (Pol II) is important for a variety of cellular functions. ELL/EAF-containing little elongation complex (LEC) was found to be required for transcription of Pol II-dependent small nuclear RNA (snRNA) genes. It was shown that the tumor suppressor p53 interacts with ELL and inhibits transcription elongation activity of ELL Here, we show that p53 inhibits interaction between ELL/EAF and ICE1 in LEC and thereby p53 represses transcription of Pol II-dependent snRNA genes through inhibiting LEC function. Furthermore, induction of p53 expression by ultraviolet (UV) irradiation decreases the occupancy of ICE1 at Pol II-dependent snRNA genes. Consistent with the results, knockdown of p53 increased both the expression of snRNA genes and the occupancy of Pol II and components of LEC at snRNA genes. Our results indicate that p53 interferes with the interaction between ELL/EAF and ICE1 and represses transcription of snRNA genes by Pol II. (C) 2016 Elsevier B.V. All rights reserved.
• 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 日本耳鼻咽喉科免疫アレルギー学会 34 (2) 179 - 180 0913-0691 2016/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 34 (2) 139 - 139 0913-0691 2016/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 34 (2) 56 - 57 0913-0691 2016/06 [Refereed][Not invited]
  
• 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 (一社)日本アレルギー学会 65 (4-5) 557 - 557 0021-4884 2016/05 [Refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 119 (4) 636 - 636 0030-6622 2016/04 [Refereed][Not invited]
  
• TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin.

  Masanobu Suzuki, Masashi Watanabe, Yuji Nakamaru, Dai Takagi, Hidehisa Takahashi, Satoshi Fukuda, Shigetsugu Hatakeyama

  Cellular and molecular life sciences : CMLS 73 (5) 1085 - 101 2016/03 [Refereed]
   

  NFκB is one of the central regulators of cell survival, immunity, inflammation, carcinogenesis and organogenesis. The activation of NFκB 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 NFκB 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 NFκB- and TLR-mediated transcriptions. We show that TRIM39 stabilizes Cactin protein and that Cactin is upregulated after TNFα stimulation. TRIM39 knockdown also causes activation of the NFκB signal. These findings suggest that TRIM39 negatively regulates the NFκB signal in collaboration with Cactin induced by inflammatory stimulants such as TNFα.
• Preoperative Assessments for Sinonasal Inverted Papilloma

  Nakamaru Yuji, Takagi Dai, Suzuki Masanobu, Homma Aya, Fukuda Satoshi

  Nihon Bika Gakkai Kaishi (Japanese Journal of Rhinology) 日本鼻科学会 55 (1) 114 - 114 0910-9153 2016
• 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) 1883-7077 2016 [Refereed]
  
• 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) 2185-5900 2016 [Refereed]
  
• 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) 2185-5900 2016 [Refereed]
  
• 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) 2185-5900 2016 [Refereed]
  
• 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 1420-3030 2016 [Refereed][Not invited]
   

  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
• 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 (株)北隆館 35 (11) 1090 - 1092 0285-6379 2015/10 [Not refereed][Not invited]
   

  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)
• 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 (一社)日本鼻科学会 54 (3) 376 - 376 0910-9153 2015/09 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 33 (3) 185 - 192 0913-0691 2015/09 [Refereed]
   

  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)
• 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 日本耳鼻咽喉科免疫アレルギー学会 33 (2) 128 - 129 0913-0691 2015/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 33 (2) 50 - 51 0913-0691 2015/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 33 (2) 38 - 39 0913-0691 2015/06 [Refereed][Not invited]
  
• 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 (一社)日本アレルギー学会 64 (3-4) 561 - 561 0021-4884 2015/04 [Refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 118 (4) 540 - 540 0030-6622 2015/04 [Refereed][Not invited]
  
• The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPAR gamma

  Masashi Watanabe, Hidehisa Takahashi, Yasushi Saeki, Takashi Ozaki, Shihori Itoh, Masanobu Suzuki, Wataru Mizushima, Keiji Tanaka, Shigetsugu Hatakeyama

  ELIFE 4 e05615  2050-084X 2015/04 [Refereed][Not invited]
   

  Adipocyte differentiation is a strictly controlled process regulated by a series of transcriptional activators. Adipogenic signals activate early adipogenic activators and facilitate the transient formation of early enhanceosomes at target genes. These enhancer regions are subsequently inherited by late enhanceosomes. PPAR gamma is one of the late adipogenic activators and is known as a master regulator of adipogenesis. However, the factors that regulate PPAR gamma expression remain to be elucidated. Here, we show that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPAR gamma protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPAR gamma protein abundance during preadipocyte differentiation, resulting in a severe defect in late adipogenic differentiation, whereas it did not affect the formation of early enhanceosomes. Our results suggest that TRIM23 plays a critical role in the switching from early to late adipogenic enhanceosomes by stabilizing PPAR gamma protein possibly via atypical polyubiquitin conjugation.
• Ubiquitin modification in otolaryngology

  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) 日本耳鼻咽喉科免疫アレルギー学会 33 (3) 185-192 (J-STAGE) - 192 2185-5900 2015 [Refereed][Not invited]
   

  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)
• ベーチェット病感受性遺伝子Tripartite motif protein 39(TRIM39)の機能解析

  SUZUKI MASANOBU, SUZUKI MASANOBU, WATABE MASASHI, NAKAMARU YUJI, TAKAGI DAI, HONMA AYA, HATAKEYAMA SHIGETSUGU, FUKUDA SATOSHI

  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 [Not refereed][Not invited]
  
• 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 (一社)日本鼻科学会 53 (3) 418 - 418 0910-9153 2014/09 [Refereed][Not invited]
  
• 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 (一社)日本鼻科学会 53 (3) 408 - 408 0910-9153 2014/09 [Refereed][Not invited]
  
• 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, 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 (一社)日本耳鼻咽喉科学会 117 (4) 504 - 504 0030-6622 2014/04 [Refereed][Not invited]
  
• 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) 1883-7077 2014 [Refereed]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 31 (2) 73 - 74 0913-0691 2013/06 [Refereed][Not invited]
  
• 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 0023-852X 2013/04 [Refereed][Not invited]
   

  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.
• 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 [Not refereed][Not invited]
  
• 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 (株)医学書院 84 (13) 1021 - 1026 0914-3491 2012/12 [Refereed][Not invited]
   

  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。
• 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 0003-4894 2012/12 [Refereed][Not invited]
   

  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.
• 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 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 215 - 216 0913-0691 2012/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 76 - 77 0913-0691 2012/06 [Refereed][Not invited]
  
• 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 日本耳鼻咽喉科免疫アレルギー学会 30 (2) 70 - 71 0913-0691 2012/06 [Refereed][Not invited]
  
• 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 (一社)日本耳鼻咽喉科学会 115 (4) 413 - 413 0030-6622 2012/04 [Refereed][Not invited]
  
• 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 (一社)日本鼻科学会 50 (3) 379 - 379 0910-9153 2011/11 [Refereed][Not invited]
  
• False-negative diffusion-weighted MRI in acute cerebellar stroke

  Shinya Morita, Masanobu Suzuki, Keiji Iizuka

  AURIS NASUS LARYNX 38 (5) 577 - 582 0385-8146 2011/10 [Refereed][Not invited]
   

  Objective: To heighten physician awareness of false-negative diffusion-weighted (DW) magnetic-resonance imaging findings in patients with acute cerebellar infarction and the importance of periodically observing nystagmus after symptom onset. Methods: Between April 2007 and March 2010, we retrospectively reviewed the medical records of eight patients who had all complained of severe isolated vertigo or dizziness, and had visited an emergency department within 2-6 h of its onset. Intracranial findings on initial magnetic resonance imaging (MRI) were normal. All patients had consulted our department for peripheral vestibular disorders. We periodically observed spontaneous and positional nystagmus 6-24 h after symptom onset. Results: In three of the patients, the direction and/or type of nystagmus changed periodically. In four of the patients, severe vertigo, nausea, and vomiting persisted after the nystagmus had been resolved. A repeat MR examination was performed 24 h after symptom onset because of the atypical pattern of nystagmus for benign peripheral vestibular disorders, at which point cerebellar infarction was detected. Conclusions: Physicians who examine patients with acute severe isolated vertigo or dizziness should consider the possibility of false-negative DW MRI findings in case of hyperacute ischemic stroke. It is important to observe the nystagmus periodically after onset. The MR examination should be repeated more than 24 h after symptom onset in patients with an atypical pattern of nystagmus for benign peripheral vestibular disorders. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
• A Case of Immunoglobulin 4-Related Disease With Bilateral Mass-Forming Lesions in the Nasolacrimal Ducts

  Masanobu Suzuki, Takatsugu Mizumachi, Shinya Morita, Kanako Kubota, Keiji Iizuka

  JCR-JOURNAL OF CLINICAL RHEUMATOLOGY 17 (4) 207 - 210 1076-1608 2011/06 [Refereed][Not invited]
   

  This case study describes a 58-year-old man with watery eyes, bilateral swelling of the ala nasi and submandibular glands, and a swollen right parotid gland. Computed tomography revealed mass-forming lesions in both nasolacrimal ducts, extending bilaterally to the lacrimal sac and inferior meatus in the nose. Pathologic investigation showed marked infiltrates of immunoglobulin 4 (IgG4)-positive plasma cells in the nasolacrimal duct lesion, which led us to diagnose IgG4-related disease. Oral prednisolone improved the symptoms of watery eyes and the bilateral swelling of the nasolacrimal duct and salivary gland enlargement. To the best of our knowledge, this is the first report of IgG4-related disease involving mass-forming lesions in the nasolacrimal ducts.
• 広頸筋皮弁を用いて再建した後期高齢者口腔癌の2症例

  鈴木 正宣, 蠣崎 文彦, 津布久 崇, 大谷 文雄, 松村 道哉, 沖田 美千子, 針谷 靖史, 関口 隆, 古田 康

  手稲渓仁会病院医学雑誌 (医)渓仁会手稲渓仁会病院 10 (1) 31 - 35 1343-3741 2011/03 [Not refereed][Not invited]
   

  広頸筋皮弁にて再建した後期高齢者口腔癌2症例を報告した。症例1は80歳女で、下顎歯肉癌(扁平上皮癌)T2N0M0と診断し、下顎骨辺縁切除+口腔底切除+左頸部郭清+広頸筋皮弁による再建術を行った。症例2は80歳女で、左下顎臼歯部の低悪性度粘表皮癌T1N0M0と診断し、下顎骨区域切除+チタンプレートによる下顎骨再建+広頸筋皮弁による口腔粘膜欠損の再建を行った。2症例とも気管切開は不要で頸部を縫縮することができたため、低侵襲かつ短時間で口腔内を再建でき、顔面動静脈と外頸静脈に工夫を凝らすことで、広頸筋皮弁は良好に生着した。広頸筋皮弁は口腔内に適した大きさと成形のしやすさから、口腔内の再建に適しており、遊離皮弁と比べて短時間で低侵襲に行えるため、後期高齢者の再建材料としても有用であると考えられた。
• 垂直上眼瞼向き眼振が改善したWernicke脳症疑いの1例

  鈴木 正宣, 宮腰 浩世, 森田 真也, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 23 (1) 93 - 96 0915-2520 2011/03 [Not refereed][Not invited]
   

  中枢性めまいを疑う典型的な眼振所見として垂直上眼瞼向き眼振があるが、稀であり、多数例をまとめた報告も少ない。今回我々はWernicke脳症が原因と考えられる垂直上眼瞼向き眼振が、経過と共に改善した1例を報告する。32歳男性。解離性遁走にて、屋外で倒れている状態で発見された。脱水、低栄養状態、見当識障害を認め、ビタミン剤を含む点滴療法が開始された。その後、歩行時のふらつきが残存し、当科紹介受診となった。初診時、右眼球の外転障害、複視と、頭位眼振検査にて急速相を上眼瞼向きに持つ垂直性の眼振を認めた。中枢性前庭障害と考え、神経内科を紹介し、見当識障害、失調性歩行、外眼筋麻痺、MRI所見からWernicke脳症と考えられた。その後、赤外線ビデオ眼球運動記録装置(video oculography:VOG)を用いて、経時的に観察したところ、垂直上眼瞼向き眼振の緩徐相速度の改善を認めた。自覚的にもふらつきやめまいなどの前庭障害は消失した。(著者抄録)
• 異物の穿通により眼窩内血腫を呈した1例

  宮腰 浩世, 鈴木 正宣, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 23 (1) 79 - 83 0915-2520 2011/03 [Not refereed][Not invited]
   

  眼窩内血腫は稀な疾患であり保存的加療で改善する例も多いが、視神経を圧迫するような例では視力予後が不良であり緊急性が高い。今回我々は転倒にて受傷し、細い棒状の異物が左鼻翼外方から鼻腔を穿通し、右眼窩内にいたり眼窩内血腫を呈した1例を経験したので報告する。症例は85歳男性。観葉植物の手入れをしていた際に意識消失し転倒、救急搬送先の病院で施行されたCTにて眼窩内異物と血腫を疑う陰影を認め、当院依頼となった。当院眼科の診察にて眼球内容は保たれているものの、血腫による眼球突出が著明であり、対光反射が消失しており、緊急手術目的に当科依頼となった。当科にて鼻内視鏡下に眼窩血腫を除去し、さらに異物摘出を試みたが摘出困難であり、外切開にて異物(骨片)を摘出した。術後ステロイド治療を施行したが、せん妄が見られたため、術後3日目で当科退院となった。外来にて現在も経過観察中であり、眼窩血腫は消退し、感染も認めないが、視力は依然失明状態であり改善が得られていない。(著者抄録)
• IgG4関連疾患が疑われた症例の検討

  鈴木 正宣, 宮腰 浩世, 森田 真也, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 23 (1) 3 - 8 0915-2520 2011/03 [Not refereed][Not invited]
   

  IgG4関連疾患は、臓器の腫大や炎症、組織の線維化を来す全身疾患である。21世紀に本邦で提唱された新しい疾患概念であり、いくつかの診断基準が提唱されている。当科でIgG4関連疾患が疑われた10症例を検討した。年齢は43歳から81歳(平均66歳)で、男性9例、女性1例であった。7例で血清IgG4の高値を認めた。全例で唾液腺、涙腺の対称性腫脹が見られ、そのうち5例で2組以上の腫脹が見られた。3例で、それぞれIgG4関連疾患に特異性が高いとされる、膵臓、前立腺、後腹膜に合併疾患を有していた。FDG-PETを施行した症例では、全ての罹患臓器に集積を認め、他臓器病変のスクリーニングや治療効果判定にはFDG-PETが有用であると考えられた。5例で副鼻腔炎などの鼻腔病変を有しており、IgG4関連疾患は高率に無症状の副鼻腔炎を合併する可能性があると考えられた。また、口腔内乾燥症を呈する症例もあり、根本治療が可能な口腔乾燥症としてIgG4関連疾患を鑑別することは重要であると考えられた。(著者抄録)
• The accuracy of (18)[F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography alone in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma.

  Shinya Morita, Kenji Mizoguchi, Masanobu Suzuki, Keiji Iizuka

  World journal of surgery 34 (11) 2564 - 9 2010/11 [Refereed]
   

  BACKGROUND: The aim of this study was to evaluate the accuracy of [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography alone in the preoperative diagnosis of lymph node metastasis in patients with papillary thyroid carcinoma. METHODS: In a prospective study performed between January 2007 and December 2009, 74 patients with a diagnosis of papillary thyroid carcinoma confirmed by fine-needle aspiration biopsy were referred to our institution for surgery. Preoperative assessment of metastasis in the central and lateral cervical lymph nodes was done using [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography, ultrasonography, and enhanced computed tomography. The results for each level of cervical node assessed using these methods were correlated with the pathology reports after surgery. We determined the sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the three methods for all levels of cervical lymph node. RESULTS: There were no significant differences in the diagnostic results obtained by [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography and enhanced computed tomography. However, ultrasonography images gave significantly better results than either [(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography/computed tomography or enhanced computed tomography alone in identifying metastases on the basis of the level of cervical lymph node. In addition, the overall diagnostic accuracy tended to be higher for the lateral compartment than for the central compartment. CONCLUSIONS: Preoperative assessment by ultrasonography of metastases in the central and lateral cervical lymph nodes might be the best methodology for determining the extent of surgical resection required to remove metastatic lymph nodes adequately in patients with papillary thyroid carcinoma.
• Regurgitation of a mass into the mouth: a fibrovascular polyp of the esophagus

  A. Goto, M. Suzuki, K. Iizuka, Y. Yoshida, K. Suzuki, M. Itoh, H. Wakasugi, K. Fujii, Y. Matunaga, Y. Shinomura

  Endoscopy 42 (S 02) E248 - E249 0013-726X 2010/10 [Refereed]
  
• A case of idiopathic lymph leakage in the neck

  Masanobu Suzuki, Shinya Morita, Keiji Iizuka

  AURIS NASUS LARYNX 37 (4) 535 - 537 0385-8146 2010/08 [Refereed][Not invited]
   

  A 48-year-old female patient was seen in our institution complaining of sudden onset of swelling and tenderness in the left side of her neck. Computed tomography and magnetic resonance imaging revealed abundant effusions in this area. Since these narrowed the patient's airway, we performed incisional drainage and intra-operatively we observed a transparent, colorless lymph fluid that oozed from the operative field, which was mainly a fatty layer at the supraclavicular area. Dilated lymphatic ducts were seen along the carotid artery and internal jugular vein, but damaged lymphatic ducts and obvious causative disease structures like tumorous lesions were not seen. Idiopathic lymph leakage was diagnosed due to the serous discharge from the left side of the neck and no apparent causative disease. The patient was successfully treated with incisional drainage and dietary restriction. Lymph leakage in the neck is more common after trauma or surgery. To our knowledge, no similar cases have ever been reported. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
• 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 (一社)日本鼻科学会 49 (3) 415 - 415 0910-9153 2010/07 [Refereed][Not invited]
  
• Non-organic hearing loss in childhood.

  Shinya Morita, Masanobu Suzuki, Keiji Iizuka

  International journal of pediatric otorhinolaryngology 74 (5) 441 - 6 2010/05 [Refereed]
   

  OBJECTIVE: The present study aimed to investigate the etiology, symptoms, diagnosis and prognosis of pediatric patients with non-organic hearing loss (NOHL), and to heighten awareness of this disorder among physicians. METHODS: Between January 2000 and July 2009, we retrospectively reviewed the medical records of 47 pediatric patients (aged 6-18 years of age) diagnosed with NOHL. The diagnosis was made when there were audiometric discrepancies between the subjective and objective hearing thresholds of the patient in the absence of any organic disease. RESULTS: Eighteen patients presented with unilateral hearing loss, and 29 showed bilateral hearing loss. Five patients received steroid treatment before the correct diagnosis was made, and six had secretory otitis media and underwent a tympanostomy tube placement. CONCLUSION: If physicians are unaware of the possibility of NOHL; they may misdiagnose children with idiopathic sudden sensorineural hearing loss and administer high-dose steroid treatments or exploratory tympanotomies. Otoacoustic emissions are abolished when NOHL patients have secretory otitis media. In these cases, after tympanostomy tube placement, they should undergo objective electrophysiologic examinations to reevaluate NOHL.
• 胸骨柄当該皮下に生じた類皮嚢胞の1例

  鈴木 正宣, 森田 真也, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 22 (1) 89 - 92 0915-2520 2010/03 [Not refereed][Not invited]
   

  類皮嚢胞は、胎生期に外胚葉成分が中胚葉に迷入することに起因する、比較的稀な嚢胞性疾患である。身体各部に発生するが、頭頸部領域の発生率は全体の6.9%であり、その内の約20%が頸部に発生する。今回、我々は胸骨柄当該皮下に発生し、完全摘出した類皮嚢胞の1例を報告する。症例は41歳、男性。幼少期から両鎖骨間の皮下腫瘤に気づいていたが、徐々に増大したため、平成21年6月当科受診した。胸骨上部から下頸部正中の両鎖骨間に30mm大の皮下腫瘤があり、エコーでは、内部に点状のhigh echoが散在する嚢胞性腫瘤を認めた。類皮嚢胞の臨床診断にて、摘出術を行った。下頸部正中を横切開し、嚢胞壁にそって完全摘出した。摘出した嚢胞は4×3.5×4cmの円形で、表面平滑な皮膜を有していた。嚢胞を切開したところ、内部から乳白色のクリーミーな液体が流出し、嚢胞内には黒い毛髪が認められた。病理学的には、角化を伴う重層扁平上皮によって嚢胞壁内面が構成されており、壁内に皮脂腺、嚢胞腔内に毛髪を認め、類皮嚢胞と診断された。(著者抄録)
• 後天性後鼻腔閉鎖症の1例

  鈴木 正宣, 森田 真也, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 22 (1) 83 - 87 0915-2520 2010/03 [Not refereed][Not invited]
   

  後鼻孔閉鎖とは後鼻孔が骨性もしくは膜性に閉鎖し、固有鼻腔と咽頭が物理的に遮断された病態である。その多くはCHARGE症候群に合併した先天性後鼻孔閉鎖症であり、5,000-7,000人に一人の出現率といわれる比較的稀な疾患である。一方、後天性後鼻孔閉鎖症は、上咽頭がんに対する放射線治療後や、レーザーを用いた扁桃摘出術後やアデノイド切除後に発生したとの報告はあるものの、誘因無く発生することは極めて稀な疾患である。後天性後鼻孔閉鎖症に対して後鼻孔開大術を施行した1例を報告する。症例は65歳、女性。22歳時に副鼻腔炎にて手術を受けた既往がある。45歳頃から鼻閉を感じていたが、2001年7月近医耳鼻科にて後鼻腔閉鎖を指摘された。当科初診時の鼻咽腔ファイバー所見で両側後鼻孔の膜性閉鎖を認めた。以前は鼻呼吸が出来たこと、22歳時に両側副鼻腔根本術を受けた際に、異常が指摘されていないこと、45歳頃から鼻閉が出現したことから、後天性後鼻孔閉鎖と診断し、後鼻孔開放術を施行した。後鼻孔は非常に厚い瘢痕にて閉鎖されており、初回手術は瘢痕を切除し、後鼻孔を開放したが、再閉鎖したため、経口蓋法による再手術を施行した。この際、経口蓋法を用いて十分な開放を行い、ステントとして左耳介軟骨を移植した。その発生機転として、上咽頭周辺の炎症性病変の持続によるものと推測され、その後、再狭窄傾向があるたびに、鼻内内視鏡下にレーザーにて再開大と周辺粘膜の焼灼を行い、現在のところ後鼻孔の開存を維持している。(著者抄録)
• 気管支喘息と誤認された気管支異物の1例

  森田 真也, 鈴木 正宣, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 22 (1) 77 - 81 0915-2520 2010/03 [Not refereed][Not invited]
   

  気道異物は呼吸困難を呈して低酸素血症から心停止に至る危険があるため、緊急性は非常に高い。今回、我々は異物を誤嚥した情報がないため気管支喘息と誤認された気管支異物症例を経験したので報告する。症例は5歳、男児で、咳嗽および喘鳴を主訴に近医小児科を受診して気管支喘息と診断された。気管支拡張薬・吸入にて治療されるも改善を認めなかったため、当院小児科を受診し、胸部単純X線写真にて右主気管支に異物を認めた。当科紹介となり、全身麻酔下にて換気孔付き硬性気管支鏡(ventilation bronchoscope)を挿入し、X線透視(術中イメージ)を併用することにより、硬性気管支鏡先端・異物鉗子・異物の位置を確認しながら摘出した。術中・術後合併症は認めず、経過良好にて術後4日で退院となった。(著者抄録)
• 上顎癌に対する超選択的動注療法

  森田 真也, 鈴木 正宣, 稲村 茂, 今泉 俊雄, 飯塚 桂司

  市立釧路総合病院医学雑誌 市立釧路総合病院 22 (1) 11 - 17 0915-2520 2010/03 [Not refereed][Not invited]
   

  上顎癌に対する治療においては、病変の解剖学的位置関係から、嚥下・咀嚼・発声・構音など様々な程度の機能障害を残す結果となる。現在、根治性を追及するだけではなく、機能障害の面も考慮に入れた治療法として超選択的動注療法が注目されている。Seldinger法による大腿動脈経由での方法と浅側頭動脈経由での方法の治療効果および有害事象の比較に関して報告する。2003年〜2009年までの期間に、当科にて超選択的動注療法と放射線照射の併用療法を施行した上顎洞原発扁平上皮癌10例を対象とした。前者にて治療した全ての症例において、原発巣CRの評価となり、平均観察期間17.2ヵ月と短期間ではあるが、局所制御に関しては良好であった。後者にて治療した全ての症例において、放射線照射40Gy/20frの時点で原発巣PRの評価であったため、切除不能症例の1例を除いて、眼窩内容を温存することが可能ではあったものの根治手術が必要となった。前者の方が発生する有害事象の頻度が多かったが、両者ともに治療中断の原因となりうる有害事象は認めなかった。前者に関しては未知の部分も多く、将来的な経過観察および長期的成績の検討も必要ではあるが、上顎癌症例において局所制御が良好であったことの意義は非常に大きい。(著者抄録)
• 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 (株)医学書院 82 (1) 67 - 72 0914-3491 2010/01 [Refereed][Not invited]
   

  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。
• [Prevention of wound complications after salvage total laryngectomy following chemoradiotherapy with a pectoralis major muscle interposition flap].

  Yasushi Furuta, Michiya Matsumura, Fumio Ohtani, Masanobu Suzuki, Hiroki Satoh, Shinya Morita, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda

  Nihon Jibiinkoka Gakkai kaiho 113 (1) 9 - 14 0030-6622 2010/01 [Refereed]
   

  There is an increased risk of wound complications in patients undergoing salvage laryngectomy following chemoradiotherapy. To reduce the rate of wound complications after a salvage total laryngectomy, a fresh tissue reinforcement of the pharyngeal suture line (pharyngeal interposition graft) has been reported to be useful. In the present study, wound complications after a salvage total laryngectomy with a pectoralis major muscle flap as a pharyngeal interposition graft were analyzed. Four patients with recurrent laryngeal cancer (three with supraglottic, and one with glottic cancer) after chemoradiotherapy underwent salvage total laryngectomy using a pectoralis major muscle interposition flap. Minor wound complications were observed in three of the four patients, with an infection around the tracheostoma, a minor subcutaneous abscess, and a superficial skin necrosis in one patient each. These complications were managed with local wound care. No patients had major wound complications such as pharyngocutaneous fistulas. There were no necroses or wound complications of the pectoralis major muscle flap. This study has suggested that the pectoralis major muscle flap as a pharyngeal interposition graft is safe and useful for prevention of wound complications in salvage total laryngectomy following chemoradiotherapy.
• A comparison of the short-term outcome in patients with acute low-tone sensorineural hearing loss.

  Shinya Morita, Masanobu Suzuki, Keiji Iizuka

  ORL; journal for oto-rhino-laryngology and its related specialties 72 (6) 295 - 9 2010 [Refereed]
   

  PURPOSE OF THE STUDY: We aimed to compare the short-term outcome of patients with acute low-tone sensorineural hearing loss (ALHL) treated with steroid alone, diuretics alone or combination treatment. PROCEDURES: Between April 2000 and March 2009, we retrospectively reviewed the medical records of 156 patients with a diagnosis of ALHL. All patients were followed up until improvement or for 8 weeks from the initial examination. Patients were treated with steroid alone (n = 49), diuretics alone (n = 40), combination treatment (n = 46) or they received neither steroid nor diuretics (n = 21). RESULTS: The steroid-diuretic combination therapy for ALHL showed significantly better results than the steroid or diuretic treatments alone (p < 0.05). There were no clinically significant differences in the outcome between the steroid- and diuretic-alone treatments. CONCLUSION AND MESSAGE: The etiology of ALHL is described as both an endolymphatic hydrops and an autoimmunological mechanism so that, as expected, the steroid-diuretic combination therapy was more effective than the steroid or diuretic treatments alone.
• Prevention of wound complications after salvage total laryngectomy following chemoradiotherapy with a pectoralis major muscle interposition flap

  Yasushi Furuta, Michiya Matsumura, Fumio Ohtani, Masanobu Suzuki, Hiroki Satoh, Shinya Morita, Akihiro Homma, Nobuhiko Oridate, Satoshi Fukuda

  Journal of Otolaryngology of Japan (一社)日本耳鼻咽喉科学会 113 (1) 9 - 14 0030-6622 2010 [Refereed][Not invited]
   

  There is an increased risk of wound complications in patients undergoing salvage laryngectomy following chemoradiotherapy. To reduce the rate of wound complications after a salvage total laryngectomy, a fresh tissue reinforcement of the pharyngeal suture line (pharyngeal interposition graft) has been reported to be useful. In the present study, wound complications after a salvage total laryngectomy with a pectoralis major muscle flap as a pharyngeal interposition graft were analyzed. Four patients with recurrent laryngeal cancer (three with supraglottis and one with glottic cancer) after chemoradiotherapy underwent salvage total laryngectomy using a pectoralis major muscle interposition flap. Minor wound complications were observed in three of the four patients, with an infection around the tracheostoma, a minor subcutaneous abscess, and a superficial skin necrosis in one patient each. These complications were managed with local wound care. No patients had major wound complications such as pharyngocutaneous fistulas. There were no necroses or wound complications of the pectoralis major muscle flap. This study has suggested that the pectoralis major muscle flap as a pharyngeal interposition graft is safe and useful for prevention of wound complications in salvage total laryngectomy following chemoradiotherapy.
• A Comparison of the Short-Term Outcome in Patients with Acute Low-Tone Sensorineural Hearing Loss

  Shinya Morita, Masanobu Suzuki, Keiji Iizuka

  ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES 72 (6) 295 - 299 0301-1569 2010 [Refereed][Not invited]
   

  Purpose of the Study: We aimed to compare the short-term outcome of patients with acute low-tone sensorineural hearing loss (ALHL) treated with steroid alone, diuretics alone or combination treatment. Procedures: Between April 2000 and March 2009, we retrospectively reviewed the medical records of 156 patients with a diagnosis of ALHL. All patients were followed up until improvement or for 8 weeks from the initial examination. Patients were treated with steroid alone (n = 49), diuretics alone (n = 40), combination treatment (n = 46) or they received neither steroid nor diuretics (n = 21). Results: The steroid-diuretic combination therapy for ALHL showed significantly better results than the steroid or diuretic treatments alone (p < 0.05). There were no clinically significant differences in the outcome between the steroid-and diuretic-alone treatments. Conclusion and Message: The etiology of ALHL is described as both an endolymphatic hydrops and an autoimmunological mechanism so that, as expected, the steroid-diuretic combination therapy was more effective than the steroid or diuretic treatments alone. Copyright (C) 2010 S. Karger AG, Basel
• 【耳鼻咽喉科診療におけるヒヤリ・ハット】 治療過程におけるヒヤリ・ハット 口腔・咽頭の手術

  鈴木 正宣, 古田 康

  ENTONI (株)全日本病院出版会 (109) 53 - 61 1346-2067 2009/12 [Not refereed][Not invited]
   

  耳鼻咽喉・頭頸部外科領域で、扁桃摘出術、アデノイド切除術を含む口腔・咽頭手術はもっとも頻繁に施行される手術の1つである。口腔・咽頭手術の多くは比較的低侵襲であるが、呼吸経路の一部でもあることから、偶発症・合併症が発生した際には、重篤な事態となる可能性がある。また、味覚・嚥下などの機能障害が起きた際には、患者のQOLに直接影響を与える。当科では、起こりうる合併症、偶発症をもれなく記載した手術説明書を用いて、十分なインフォームドコンセントを得てから手術を施行している。万が一、合併症が生じた場合には迅速に対応することを心がけている。また、合併症だけではなくクレームに対しても早期に対応するようにしている。電子カルテは情報が一元化されるため、クレーム対応においても有用である。(著者抄録)
• 喉頭微細手術におけるコロラドマイクロディセクションニードルの使用について

  鈴木 正宣, 大谷 文雄, 松村 道哉, 古田 康

  日本気管食道科学会会報 (NPO)日本気管食道科学会 60 (6) 507 - 511 0029-0645 2009/12 [Refereed][Not invited]
   

  コロラドマイクロディセクションニードルはチップ先端が5ミクロンと極めて鋭利なモノポーラ針である。最長で有効長17.8cmのプローブもあり、直達喉頭鏡下手術においても使用できる。通常のモノポーラーと同様、止血能に優れ、さらに先端が極めて鋭利であるので周囲組織障害を起こしにくい。また安価であり、汎用されている一般のメスホルダーに接続可能であるため、レーザーに比べ導入は容易である。当科においては直達喉頭鏡下の喉頭蓋嚢胞造袋術、喉頭蓋血管腫切除術、喉頭腫瘍切除術で切開、凝固、止血に使用してきた。コロラドマイクロディセクションニードルを使用した喉頭微細手術の手技と工夫について述べる。(著者抄録)
• 咽喉頭酸逆流症に対するラベプラゾール投与による咽喉頭所見の検討(第2報)

  折舘 伸彦, 田口 亜紀, 渡嘉敷 亮二, 渡邊 雄介, 目須田 康, 鈴木 正宣, 新谷 朋子, 金泉 悦子, 丸子 文, 濱島 有喜, 吉岡 正展, 細川 清人, 後藤 理恵子, 印藤 加奈子, 山本 美佐子

  日本気管食道科学会会報 (NPO)日本気管食道科学会 60 (2) 210 - 210 0029-0645 2009/04 [Refereed][Not invited]
  
• 咽喉頭酸逆流症に対するラベプラゾール投与による咽喉頭所見の検討(第1報)

  田口 亜紀, 折館 伸彦, 渡嘉敷 亮二, 渡邊 雄介, 目須田 康, 鈴木 正宣, 新谷 朋子, 金泉 悦子, 丸子 文, 濱島 有喜, 吉岡 正展, 細川 清人, 後藤 理恵子, 印藤 加奈子, 山本 美佐子

  日本気管食道科学会会報 (NPO)日本気管食道科学会 60 (2) 168 - 168 0029-0645 2009/04 [Refereed][Not invited]
  
• 喉頭直達鏡下手術におけるコロラドマイクロディセクションニードルの使用経験

  鈴木 正宣, 大谷 文雄, 松村 道哉, 古田 康

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 112 (4) 334 - 334 0030-6622 2009/04 [Refereed][Not invited]
  
• 眼球運動検査により経過を追えた家族性片麻痺性片頭痛I型の1例

  武市 紀人, 鈴木 正宣, 藤原 圭志, 津布久 崇, 福田 諭, 矢部 一郎, 佐々木 秀直

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 112 (4) 300 - 300 0030-6622 2009/04 [Refereed][Not invited]
  
• 咽喉頭逆流症状に対するプロトンポンプ阻害剤投与による咽喉頭所見の検討(第3報)

  折舘 伸彦, 渡嘉敷 亮二, 渡邊 雄介, 田口 亜紀, 新谷 朋子, 金泉 悦子, 目須田 康, 鈴木 正宣, 丸子 文, 濱島 有喜, 吉岡 正展, 細川 清人, 後藤 理恵子, 印藤 加奈子, 山本 美佐子

  日本耳鼻咽喉科学会会報 (一社)日本耳鼻咽喉科学会 112 (4) 291 - 291 0030-6622 2009/04 [Refereed][Not invited]
  
• 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 (株)医学書院 81 (3) 219 - 221 0914-3491 2009/03 [Refereed][Not invited]
   

  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。
• 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
• 治療経過を追えた家族性片麻痺性片頭痛I型の1例

  鈴木 正宣, 武市 紀人, 藤原 圭志, 津布久 崇, 福田 諭, 矢部 一郎, 佐々木 秀直

  Equilibrium Research (一社)日本めまい平衡医学会 67 (5) 411 - 411 0385-5716 2008/10 [Refereed][Not invited]
  
• 前縦隔発生の胚細胞腫瘍の一例

  鈴木 正宣, 吉田 貴之, 呉屋 裕樹, 秋江 研志, 小倉 滋明, 高田 明生

  市立札幌病院医誌 市立札幌病院 65 (2) 297 - 298 0288-6073 2005/12 [Not refereed][Not invited]
   

  22歳男.健康診断で胸部異常陰影を指摘され受診した.胸部CTで前縦隔に軟部組織腫瘍を認め,肺動脈浸潤を認めた.経皮針生検にてセミノーマの所見であった.大血管浸潤のため手術不能と判断し,BEP療法(CDDP,VP-16,BLM)を4コース行い,重篤な副作用なしに良好な効果を得ることができた.今後,呼吸外科にて手術の予定である

Books etc

• ウォーモルド直伝 内視鏡下鼻副鼻腔手術トレーニング[Web動画付]

  鈴木, 正宣, 中薗, 彬, 志津木, 健, 本間, 明宏, 中丸, 裕爾 
  医学書院 2023/12 (ISBN: 4260052403) 264
• Learning from Nature: Naturally Derived Remedies

  Masanobu Suzuki 
  Springer 2022/09 (ISBN: 9783031109911)
• ウォーモルド内視鏡下鼻副鼻腔・頭蓋底手術

  Wormald, P. J, 鈴木, 正宣, 本間, 明宏, 中丸, 祐爾 
  医学書院 2020/09 (ISBN: 9784260042000) xvi, 309p

MISC

• 【耳鼻咽喉科手術における術中出血を減らす工夫】内視鏡下鼻副鼻腔手術

  山田 真司, 鈴木 正宣  耳鼻咽喉科  1-  (4)  429  -436  2022/04
• 耳鼻咽喉科頭頸部外科のOff-the-Job Training PCアプリを用いたESS術前プランニングのOff-the-Jobトレーニング

  鈴木 正宣  日本耳鼻咽喉科頭頸部外科学会会報  125-  (4)  539  -540  2022/04
• ARナビゲーションと3Dプリンターで切り拓く新しい鼻科手術の臨床と教育

  鈴木 正宣  日本耳鼻咽喉科頭頸部外科学会会報  125-  (4)  673  -673  2022/04
• 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  2022/04
• 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  2022/04
• 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  2022/03
• 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  2022/03
• 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  2022/03
• 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  2022/03
• 鼻腔組織からのRNA抽出およびqPCR解析(ビデオ講習)

  鈴木 正宣, 中薗 彬  日本鼻科学会会誌  60-  (3)  233  -233  2021/09
• 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  2021/09
• 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  2021/09
• 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  2021/05
• 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  2017/09
• 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  2017/04  [Not refereed][Not invited]
  

Awards & Honors

• 2024/04 ISIAN 2024 Abstract Grand Award
  

Research Grants & Projects

• Type2炎症による鼻粘膜支持組織への影響

  日本学術振興会：科学研究費助成事業 若手研究

  Date (from‐to) : 2022/04 -2026/03 

  Author : 鈴木 正宣
• 好酸球性副鼻腔炎におけるSIRT1によるサイトカイン発現制御機序の解明

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists

  Date (from‐to) : 2018/04 -2022/03 

  Author : 鈴木 正宣

   

  本年度は、好酸球性副鼻腔炎で頻発する鼻ポリープに関するサイトカインであるMMP9のSIRT1による制御について検討した。 まず、鼻粘膜上皮初代継代細胞に、Poly(I:C)とSIRT1活性剤・阻害剤を投与し、qPCR法とELISA法にてMMP9の発現を確認した。Poly(I:C)によってMMP9が誘導されることが明らかになった。Poly(I:C)の投与がなければ、MMP9の発現はSIRT1活性剤・阻害剤に影響されなかったが、Poly(I:C)が投与された場合、SIRT1活性剤・阻害剤によってMMP9の発現が制御されることが明らかになった。またZymogram法で活性を評価したが、発現と同じく活性もSIRT1の活性剤・阻害剤にて変化することがわかった。 また、鼻茸を伴う副鼻腔炎、伴わない副鼻腔炎、健常例由来の鼻粘膜によって構成されたTissue micro arrayを使い、蛍光免疫染色法にてMMP9とSIRT1の発現の間の相関を確認した。また、MMP9とSIRT1の鼻粘膜局所発現部位について検討した。いずれも、SIRT1がMMP9の発現を制御することを示唆する結果であった。 MMP9はNFKBのターゲット遺伝子であることから、他のNFKBターゲット遺伝子にも同様の制御が存在する可能性がある。現在、SIRT1によって制御されている他のサイトカインを網羅的に検索するため、microfluidic qPCR法やMultiplex ELISA法にて検討を重ねている。
• 細胞内亜鉛とTGF-βシグナル制御による好酸球性副鼻腔炎の新規治療法の開発

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))

  Date (from‐to) : 2019 -2021 

  Author : 鈴木 正宣

   

  近年、難治性副鼻腔炎は増加傾向にある。中でも鼻茸を伴う副鼻腔炎 (Chronic rhinosinusitis with nasal polyps; CRSwNP 好酸球性副鼻腔炎の多くの症例がこれに該当する。ヨーロッパの最新のガイドラインEPOS2020ではPrimary, diffuse, Type2, CRSに分類される)に対して治療戦略上のブレイクスルーが期待されている。その病態はA. 鼻粘膜上皮のバリア機能の低下を背景としたTSLPやインターロイキン33等のサイトカイン産生亢進を契機に、B. Th2優位の免疫応答（Type2炎症）が生じ、その結果として、 C. リモデリングが生じフィブリン網形成やコラーゲンの低下による浮腫が遷延し、鼻茸が形成されると考えられている。申請者らのグループはCRSwNPにおいて、鼻粘膜組織中にみられる亜鉛が低下していることを明らかにした。そこで、本研究課題ではこの組織中低亜鉛が上記のそれぞれの病態にどのように関与しているかを明らかにすることを目的としている。
  本年度は、副鼻腔炎における低亜鉛を引き起こす原因を同定するために、メタロサイオニンの発現に注目した。メタロサイオニンは2価の陽イオンのキレート作用を持つタンパク質である。メタロサイオニンのプロモーター領域には亜鉛レスポンスエレメントが存在し、その発現を制御している。すなわち、細胞質内の亜鉛が増えるとメタロサイオニンの発現が亢進し、細胞質内の亜鉛をキレートし細胞内亜鉛ホメオスタシスを保っている。本研究によって、組織中低亜鉛とメタロサイオニン3の発現には相関があることが判明した。ただ、既報と総合的に鑑みると、今回同定されたメタロサイオニン3の発現低下は、低亜鉛の原因ではなく結果と考えられた。
• 好酸球性副鼻腔炎の根治を施行したSIRT-1活性化剤の基礎的研究

  Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up

  Date (from‐to) : 2017/08 -2019/03 

  Author : 鈴木 正宣

   

  本年度は、鼻粘膜上皮初代継代細胞（HNEC）を用いて、SIRT1によるサイトカイン発現制御を検討した。 まず、HNECにおける自然免疫シグナルを検討するため、TLR1-9のアゴニストをそれぞれ投与し、mRNAレベルでのサイトカイン発現を検討した。結果、TLR3のアゴニストであるPoly (I:C)によってサイトカイン発現が有意に亢進することがわかった。Poly(I:C)にはTLR3のみならずRIG-I受容体を介して自然免疫シグナルを活性化することがわかっている。RIG-IとTLR3の特異的アゴニストをそれぞれ用いて、サイトカインmRNAの発現を検討したところ、Poly(I:C)はTLR3を介してHNECの自然免疫シグナルを活性化させることが判明した。 次に、SIRT1の活性剤と抑制剤をPoly(I:C)とともにHNECに投与。サイトカインの一つであるMMP9のmRNA、蛋白質の発現、活性を評価した。SIRT1の活性剤はPoly(I:C)に誘導されるMMP9の発現、活性を抑制させた。逆に、SIRT1の抑制剤はPoly(I:C)に誘導されるMMP9の発現、活性を亢進させた。現在、他のサイトカインへのSIRT1の影響を、microfluidic qPCR法、multiplex ELISA法で網羅的に検討中である。 また、自然免疫シグナルにおけるSIRT1の発現変化を検討中である。これまでにqPCR法、蛍光抗体免疫染色法では自然免疫シグナルの活性化によりSIRT1がmRNAと蛋白質レベルで発現亢進していると示唆される結果を得ている。現在、SIRT1活性の測定を試みているところである。

Social Contribution

Social Contribution

Social Contribution

• アデレード内視鏡副鼻腔手術講習会 運営委員

  Date (from-to) : 2022/11/24

  Role : Planner
• Advanced FESS course in Adelaide

  Date (from-to) : 2019/11/28

  Role : Lecturer

  Sponser, Organizer, Publisher  : Otolaryngology-Head and Neck surgery of Adelaide Univercity

Academic Contribution

• 第6回臨床アレルギー講習会 講師

  Date (from-to) :2023/09/24-2023/09/24

  Role: Panel chair etc

  Type: Academic society etc
• 第5回臨床アレルギー講習会 講師

  Date (from-to) :2022/09/11-2022/09/11

  Role: Planning etc

  Type: Competition etc
• IFOS World course on Sinus

  Date (from-to) :2022/03/18-2022/03/18

  Role: Planning etc

  Type: Academic society etc
• 第4回臨床アレルギー講習会 講師

  Date (from-to) :2021/09/26

  Role: Others

  Organizer, responsible person: 日本アレルギー学会
• 第3回臨床アレルギー講習会 講師

  Date (from-to) :2020/11/03

  Role: Others

  Organizer, responsible person: 日本アレルギー学会
• 第2回臨床アレルギー講習会 講師

  Date (from-to) :2019/08/25

  Role: Others

  Type: Academic society etc

  Organizer, responsible person: 日本アレルギー学会
• 第1回臨床アレルギー講習会 講師

  Date (from-to) :2018/09/02-2018/09/02

  Role: Others

  Type: Academic society etc

  Organizer, responsible person: 日本アレルギー学会