Publications by authors named "Masanobu Suzuki"

45 Publications

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.

Otol Neurotol 2021 Nov 19. Epub 2021 Nov 19.

Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAO.0000000000003431DOI Listing
November 2021

Remote Training of Functional Endoscopic Sinus Surgery With Advanced Manufactured 3D Sinus Models and a Telemedicine System.

Front Surg 2021 1;8:746837. Epub 2021 Oct 1.

Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Central Adelaide Local Health Network and the University of Adelaide, Adelaide, SA, Australia.

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. 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. 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 ( = 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, = 0.014). Questionnaires showed the course's general benefit was 95.47 ± 5.13 in dissectors and 89.24 ± 15.75 in audiences. 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fsurg.2021.746837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517106PMC
October 2021

Pediatric allergic fungal rhinosinusitis: optimizing outcomes.

Curr Opin Otolaryngol Head Neck Surg 2021 Dec;29(6):510-516

Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Central Adelaide Local Health Network and the Department of Surgery, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOO.0000000000000761DOI Listing
December 2021

[A CASE OF SEVERE ASTHMA WHO REQUIRED A SWITCH OF FOUR BIOLOGICS: DIFFERENTIAL RESPONSES ON UPPER AND LOWER AIRWAYS].

Arerugi 2021 ;70(4):315-320

Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15036/arerugi.70.315DOI Listing
June 2021

Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells.

Front Cell Infect Microbiol 2021 26;11:655666. Epub 2021 Apr 26.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.655666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107375PMC
June 2021

Objective evaluation of caudal deviation of the nasal septum and selection of the appropriate septoplasty technique.

Auris Nasus Larynx 2021 May 6. Epub 2021 May 6.

Department of Otolaryngology-Head & Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2021.04.012DOI Listing
May 2021

Enhanced Angiogenesis in Salivary Duct Carcinoma Ex-Pleomorphic Adenoma.

Front Oncol 2020 22;10:603717. Epub 2021 Feb 22.

Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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 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 . 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 . 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 . 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.603717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937931PMC
February 2021

Metallothionein-3 is a clinical biomarker for tissue zinc levels in nasal mucosa.

Auris Nasus Larynx 2021 Oct 30;48(5):890-897. Epub 2021 Jan 30.

Department of Surgery-Otorhinolaryngology Head and Neck Surgery, the Queen Elizabeth Hospital, and the University of Adelaide, Adelaide, SA 5061, Australia. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2021.01.019DOI Listing
October 2021

Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases.

Allergol Int 2021 Apr 27;70(2):190-200. Epub 2020 Oct 27.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Hokkaido, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.alit.2020.09.007DOI Listing
April 2021

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

Commun Biol 2020 10 20;3(1):592. Epub 2020 Oct 20.

Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-Ku, Sapporo, Hokkaido, 060-8638, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s42003-020-01328-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576197PMC
October 2020

[A CASE OF SEVERE ASTHMA SWITCHED TO MEPOLIZUMAB DUE TO LATE-OCCURRING UNRESPONSIVENESS TO BENRALIZUMAB].

Arerugi 2020 ;69(8):678-682

Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15036/arerugi.69.678DOI Listing
November 2020

Preoperative Pulmonary Function Testing to Predict Recurrence of Chronic Rhinosinusitis With Nasal Polyps.

Allergy Rhinol (Providence) 2020 Jan-Dec;11:2152656720946994. Epub 2020 Jul 29.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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 (%FEV) in the recurrent group was significantly lower than that in the non-recurrent group ( = .005). A multivariable logistic regression model revealed that %FEV was a positive predictor of recurrence (odds ratio: 0.96, 95% CI: 0.92-0.99,  = .023). There were no significant differences in the other pulmonary functions between the two groups.

Conclusions: We found that %FEV may be a predictor of CRSwNP recurrence after surgery. As %FEV is a pulmonary function test that is routinely performed before surgery, this parameter is readily applicable. Moreover, as %FEV appears to have the potential to reveal concealed asthma, %FEV might be a particularly useful tool for the prediction of CRSwNP recurrence after surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2152656720946994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418235PMC
July 2020

The role of endoscopic resection for selected patients with sinonasal squamous cell carcinoma.

Auris Nasus Larynx 2021 Feb 25;48(1):131-137. Epub 2020 Jul 25.

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, West 7 North 15, Sapporo 060-8638, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anl.2020.06.014DOI Listing
February 2021

Comparison of clinical characteristics of the nasal manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) and eosinophilic chronic rhinosinusitis (ECRS).

Allergol Int 2021 Jan 4;70(1):143-144. Epub 2020 Jul 4.

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Hokkaido, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.alit.2020.05.009DOI Listing
January 2021

-Induced Barrier Disruption Correlates With Elastase Activity and Marks Chronic Rhinosinusitis Severity.

Front Cell Infect Microbiol 2019 27;9:38. Epub 2019 Feb 27.

Department of Surgery-Otolaryngology Head and Neck Surgery, University of Adelaide, Adelaide, SA, Australia.

causes severe chronic respiratory diseases and is associated with recalcitrant chronic rhinosinusitis (CRS). exoproteins contain virulence factors and play important roles in the pathogenicity of , however their role in CRS pathophysiology remains unknown. We isolated 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 exoproteins or purified elastase, followed by measuring Transepithelial Electrical Resistance (TEER), permeability of FITC-dextrans, western blot, and immunofluorescence. 14/21 CIs had a significant increase in elastase activity in stationary phase of growth. There was a highly significant strong correlation between the elastase activity of CIs with mucosal barrier disruption evidenced by increased permeability of FITC-dextrans ( = 0.95, = 0.0004) and decreased TEER ( = -0.9333, < 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 elastase activity of CIs and CRS disease severity (for log phase, = 0.5631, = 0.0097; for stationary phase, = 0.66, = 0.0013) assessed by CT imaging of the paranasal sinuses. Our results implicate exoproteins as playing a major role in the pathophysiology of associated CRS by severely compromising mucosal barrier structure and function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2019.00038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400838PMC
November 2019

The Diagnostic and Clinical Utility of the Myeloperoxidase-DNA Complex as a Biomarker in Otitis Media With Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

Otol Neurotol 2019 02;40(2):e99-e106

Department of Otolaryngology - Head and Neck Surgery.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAO.0000000000002081DOI Listing
February 2019

Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing.

Int J Clin Oncol 2018 Oct 19;23(5):835-843. Epub 2018 May 19.

Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-018-1296-1DOI Listing
October 2018

Sirtuin-1 Controls Poly (I:C)-Dependent Matrix Metalloproteinase 9 Activation in Primary Human Nasal Epithelial Cells.

Am J Respir Cell Mol Biol 2018 10;59(4):500-510

1 Department of Surgery-Otorhinolaryngology Head and Neck Surgery, the Queen Elizabeth Hospital, and the University of Adelaide, Adelaide, South Australia, Australia; and.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1165/rcmb.2017-0415OCDOI Listing
October 2018

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.

Otol Neurotol 2018 04;39(4):e257-e262

Faculty of Health Sciences.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MAO.0000000000001708DOI Listing
April 2018

Cirsium maritimum Makino Inhibits the Antigen/Immunoglobulin-E-Mediated Allergic Response In Vitro and In Vivo.

J Agric Food Chem 2017 Sep 19;65(38):8386-8391. Epub 2017 Sep 19.

Department of Nutrition, University of Kochi , Kochi, Kochi 781-8515, Japan.

We investigated whether Cirsium maritimum Makino can inhibit immunoglobulin-E-mediated allergic response in rat basophilic leukemia (RBL-2H3) cells and passive cutaneous anaphylaxis (PCA) in BALB/c mice. In vitro, the ethyl acetate extract of C. maritimum Makino (ECMM) significantly inhibited β-hexosaminidase release and decreased intracellular Ca levels in RBL-2H3 cells. Moreover, ECMM leaves more strongly suppressed the release of β-hexosaminidase than ECMM flowers. ECMM leaves also significantly suppressed the PCA reaction in the murine model. High-performance liquid chromatography and H and C nuclear magnetic resonance indicated that cirsimaritin, a flavonoid, was concentrated in active fractions of the extract. Our findings suggest that ECMM leaves have a potential regulatory effect on allergic reactions that may be mediated by mast cells. Furthermore, cirsimaritin may be the active anti-allergic component in C. maritimum Makino.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.7b03322DOI Listing
September 2017

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

J Neurol Sci 2016 Sep 12;368:206-8. Epub 2016 Jul 12.

Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Hokkaido University, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2016.07.020DOI Listing
September 2016

The evaluation of the synergistic effect of 3-(2,4-dihydroxyphenyl)propionic acid and l-ascorbic acid on tyrosinase inhibition.

Z Naturforsch C J Biosci 2017 Mar;72(3-4):119-121

Faculty of Agriculture, Kochi University, Nankoku, Japan.

3-(2,4-Dihydroxyphenyl)propionic acid (DDPA) and l-ascorbic acid (vitamin C) show tyrosinase inhibition activity. A synergistic effect on tyrosinase inhibition was observed when the two compounds were mixed. The effect significantly decreased the IC50 value of both compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/znc-2016-0095DOI Listing
March 2017

p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex.

Biochim Biophys Acta 2016 08 3;1859(8):975-82. Epub 2016 Jun 3.

Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbagrm.2016.06.001DOI Listing
August 2016

Otologic and Rhinologic Manifestations of Eosinophilic Granulomatosis with Polyangiitis.

Audiol Neurootol 2016 27;21(1):45-53. Epub 2016 Jan 27.

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000442040DOI Listing
December 2016

TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin.

Cell Mol Life Sci 2016 Mar 12;73(5):1085-101. Epub 2015 Sep 12.

Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-015-2040-xDOI Listing
March 2016

The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ.

Elife 2015 Apr 23;4:e05615. Epub 2015 Apr 23.

Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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. PPARγ is one of the late adipogenic activators and is known as a master regulator of adipogenesis. However, the factors that regulate PPARγ expression remain to be elucidated. Here, we show that a novel ubiquitin E3 ligase, tripartite motif protein 23 (TRIM23), stabilizes PPARγ protein and mediates atypical polyubiquitin conjugation. TRIM23 knockdown caused a marked decrease in PPARγ 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 PPARγ protein possibly via atypical polyubiquitin conjugation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.05615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426667PMC
April 2015

New 3-O-Alkyl-4a,10a-dihydrofusarubins produced by Fusarium sp. Mj-2.

Biosci Biotechnol Biochem 2013 7;77(2):271-5. Epub 2013 Feb 7.

Department of Agricultural Chemistry, Faculty of Agriculture, Tottori University, Koyama, Tottori, Japan.

Five new 3-O-alkyl-4a,10a-dihydrofusarubins (2-6) were isolated from the culture filtrate of a strain of Fusarium sp. (Mj-2), together with the known metabolite, anhydrofusarubin (1). The structures of the new metabolites were elucidated by spectroscopic analyses to be 3-O-butyl, 3-O-3'-methylbutyl, 3-O-2'-methylbutyl and 3-O-2'-phenylethyl-4a,10a-dihydrofusarubin A, and an isomer of 3-O-2'-phenylethyl-4a,10a-dihydrofusarubin A. Their antifungal and antibacterial activities were evaluated together with a 3-O-methyl derivative (7) prepared from 3-O-butyl-4a,10a-dihydrofusarubin A (2), indicating that the size of the O-substituent at C-3 in the 4a,10a-dihydrofusarubins negatively affected the metabolites' antimicrobial activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1271/bbb.120670DOI Listing
August 2013

Dysregulation of histone deacetylase and histone acetyltransferase in development of Wegener's granulomatosis.

Ann Otol Rhinol Laryngol 2012 Dec;121(12):816-20

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/000348941212101208DOI Listing
December 2012

Nasal manifestations of immunoglobulin G4-related disease.

Laryngoscope 2013 Apr 20;123(4):829-34. Epub 2012 Nov 20.

Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/lary.23792DOI Listing
April 2013
-->