Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00125&link_issn=&doc_id=20200917530133&doc_link_id=10.4295%2Faudiology.63.428&url=https%3A%2F%2Fdoi.org%2F10.4295%2Faudiology.63.428&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J00125&link_issn=&doc_id=20200917530031&doc_link_id=10.4295%2Faudiology.63.326&url=https%3A%2F%2Fdoi.org%2F10.4295%2Faudiology.63.326&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：English  

TNF receptor II is expressed on ILC2s and TNF is able to induce production of type 2 cytokines in human ILC2s. TNF may play a role in causing or amplifying type 2 immunity contributing to health and disease.

DOI： 10.1016/j.jaci.2019.09.001

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation with accumulation of activated group 2 innate lymphoid cells (ILC2s) and elevation of thymic stromal lymphopoietin (TSLP). A member of the TNF superfamily (TNFSF), TNFSF15, is known to induce the production of type 2 cytokines in ILC2s. Although ILC2s have been implicated in CRSwNP, the presence and role of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP has not been elucidated. Here, we investigate the involvement of TNFSFs in ILC2-mediated type 2 inflammation in CRSwNP. We found that receptor activator of NF-κB (RANK) ligand (RANK-L (TNFSF11)) was significantly elevated in nasal polyps (NPs), and that the receptor of RANK-L, RANK, was expressed on ILC2s in human peripheral blood and NPs. An agonistic antibody against RANK induced production of type 2 cytokines in human ILC2s, and TSLP significantly enhanced this reaction. The membrane-bound RANK-L was detected mainly on CD45 + immune cells, including TH2 cells in NPs. The co-culture of NP-derived ILC2s and TH2 cells significantly enhanced production of type 2 cytokines, and anti-RANK-L monoclonal antibody suppressed this enhancement. In conclusion, RANK-L, together with TSLP, may play an inductive role in the ILC2-mediated type 2 inflammation in CRSwNP.

DOI： 10.1038/s41385-019-0215-8

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00125&link_issn=&doc_id=20191015460157&doc_link_id=10.4295%2Faudiology.62.504&url=https%3A%2F%2Fdoi.org%2F10.4295%2Faudiology.62.504&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00125&link_issn=&doc_id=20191015460045&doc_link_id=10.4295%2Faudiology.62.392&url=https%3A%2F%2Fdoi.org%2F10.4295%2Faudiology.62.392&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本聴覚医学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J00125&link_issn=&doc_id=20191015460202&doc_link_id=10.4295%2Faudiology.62.549&url=https%3A%2F%2Fdoi.org%2F10.4295%2Faudiology.62.549&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.

DOI： 10.1111/1348-0421.12563

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Language：Japanese   Publisher：(株)東京医学社  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.

DOI： 10.1111/nyas.13456

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Language：English   Publishing type：Research paper (scientific journal)  

Disruption of nasal epithelial tight junctions (TJs) and ciliary dysfunction are found in patients with chronic rhinosinusitis (CRS) and nasal polyps (NPs), along with an increase of p63-positive basal cells and histone deacetylase (HDAC) activity. To investigate these mechanisms, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were transfected with siRNAs of TAp63 and ΔNp63, treated with the NF-kB inhibitor curucumin and inhibitors of HDACs, and infected with respiratory syncytial virus (RSV). In TERT-HNECs, knockdown of p63 by siRNAs of TAp63 and ΔNp63, induced claudin-1 and -4 with Sp1 activity and enhanced barrier and fence functions. The knockdown of p63 enhanced the number of microvilli with the presence of cilia-like structures. Treatment with curcumin and inhibitors of HDACs, or infection with RSV prevented expression of p63 with an increase of claudin-4 and the number of microvilli. The knockdown or downregulation of p63 inhibited phospho-p38MAPK, and the p38MAPK inhibitor downregulated p63 and upregulated the barrier function. Thus, epithelial barrier and ciliogenesis of nasal epithelium are regulated in a p63-negative manner in normal and upper airway diseases. Understanding of the regulation of p63/p38 MAPK/NF-κB may be important in the therapy for airway allergy and its drug delivery system.

DOI： 10.1038/s41598-017-11481-w

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Language：Japanese   Publisher：(一社)日本鼻科学会  

Ichushi

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

CONCLUSION: This is the first report to investigate the correlation between ear anomalies related to the development of specific ear structures and chorda tympani dysfunction (CTD) in congenital microtia. CTD is not always consistent with the severity of the ear anomaly or the presence of facial nerve paralysis (FNP). OBJECTIVES: To investigate the relationship between the severity of ear anomalies and CTD as well as FNP in congenital microtia. METHODS: A retrospective assessment was performed for all patients with microtia over the period 2010-2016. All ears were graded based on the severity of ear deformity using the Jahrsdoerfer system, based on findings on computed tomography of the temporal bone. Electrogustometry (EGM) was performed to evaluate CTD. RESULTS: The group included 110 male and 62 female patients. The right ear was the most commonly affected (right 106, left 47). Eighteen patients (10.5%) had abnormal EGM thresholds. The mean (± SD) Jahrsdoerfer scores in the without CTD and positive for CTD groups were 6.53 ± 0.32 and 7.06 ± 0.37, respectively. In terms of sub-total points, there was no significant correlation between anatomic structure and CTD. There was no significant correlation between CTD and the presence of FNP.

DOI： 10.1080/00016489.2016.1278306

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Ichushi

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Language：Japanese   Publisher：(株)医学書院  

Ichushi

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Language：Japanese   Publisher：(一社)日本病理学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

Macrolide antibiotics have immunomodulatory activities, including suppression of cytokine production, cell adhesion molecule expression, and mucin production. These immunomodulatory activities improve the symptoms of respiratory diseases associated with chronic inflammation. However, the underlying molecular mechanism(s) is not well understood yet. To address this, we prepared clarithromycin (CAM)-conjugated Sepharose and examined bound cellular proteins by proteome analysis. We identified mitochondrial proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25-like protein homolog (NIP-SNAP)-1 and -2 and very long-chain acyl-CoA dehydrogenase (VLCAD) as CAM-binding proteins. Production of proinflammatory cytokines (IL-8 and IL-6) induced by lipopolysaccharides (LPSs) and Pam3-CSK4 in human epithelial cell lines BEAS-2B and T24 were suppressed by knockdown of NIP-SNAP-1 or -2, and partly by knockdown of VLCAD. Also, knockdown of NIP-SNAP-1 or -2 in various cell lines suppressed LPS-induced expression of IL-8 and IL-6 mRNA and NF-κB activity. Thus, CAM suppresses NF-κB-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2.

DOI： 10.1016/j.bbrc.2016.12.100

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.anl.2016.05.011

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Lipid mediators such as leukotrienes and lipoxines broadly regulate innate and acquired immunity, and their dysfunction causes various immune-mediated disorders. We previously reported a salient feature of arachidonate 5-lipoxyganase (Alox5), which is responsible for the production of such lipid mediators, in the regulation of high affinity antibodies in vivo. The aim of this study was to determine the functional significance of Alox5-related lipid mediators during the processes of acquired humoral responses. The results of in vitro experiments using lymphocytes in tonsils and blood specimens showed that lipoxin A4 (LXA4) and leukotriene B4 (LTB4) have the capacity to differentiate naïve CD4+ T cells into T follicular helper (Tfh) cells, which activate naïve B cells to form germinal centers. Such a function of LXA4 was further supported by results of in vitro studies using BML-111 and BOC-2, which are an agonist and an antagonist, respectively, of FPR2 of an LXA4-specific cell-surface receptor. The results suggest that such lipid mediators have a potential role in the development of lymphoid follicles through the regulation of Tfh cell differentiation.

DOI： 10.1016/j.imlet.2016.11.006

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Language：Japanese   Publishing type：Research paper (scientific journal)  

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MAO.0000000000001048

PubMed

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OBJECTIVE: Patients with multiple sensory deficits, including hearing loss and visual impairment, present a unique problem. We evaluated the clinical outcomes of cochlear implantation in patients with severe to profound sensorineural hearing loss and visual impairment. METHODS: We retrospectively reviewed eight patients with severe sensorineural hearing loss and visual impairment who underwent cochlear implantation at our institution between 1993 and 2014. The follow-up period was between 2 and 20 years. We evaluated the case histories, etiologies of hearing loss and visual impairment, pre- and postoperative pure-tone thresholds, speech perception rates after CI using the Japanese CD speech discrimination scoring system (CI-2004 test) for words and sentences, and pre- and postoperative communication means. Postoperative speech discrimination scores were compared between patients with and without visual impairment who underwent cochlear implantation. RESULTS: The outcomes of cochlear implantation were good in all patients, with seven showing the ability to hold a conversation with others. The average proportion of correct answers for words and sentences in the CI-2004 test was 72.3 ± 19.1% and 86.0 ± 16.1%, respectively, for the patients with visual impairment and 62.1 ± 21.7% and 78.5 ± 20.9%, respectively, for those without visual impairment (based on auditory senses only). There were no significant differences in results between the patients with and without visual impairment. CONCLUSIONS: Cochlear implantation is important for the rehabilitation of patients with severe auditory loss and visual impairment. Medical staff members require additional skills to perform auditory evaluations and rehabilitate patients with multiple sensory deficits.

DOI： 10.1016/j.anl.2015.08.005

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Language：Japanese   Publisher：(一社)日本細胞生物学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000441868

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medquest Communications LLC  

PubMed

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Language：English   Publishing type：Research paper (scientific journal)  

Cochlear implantation (CI) has proven to be an effective treatment for severe bilateral sensorineural hearing loss (SNHL). Inner ear malformation is a rare anomaly and occurs in approximately 20% of cases with congenital SNHL. In cases with cochlear malformation, CI can be successfully performed in nearly all patients, the exceptions being those with complete labyrinthine and cochlear aplasia. It is important to evaluate the severity of inner ear deformity and other associated anomalies during the preimplantation radiological assessment in order to identify any complication that may potentially occur during the surgery and subsequent patient management.

DOI： 10.1159/000441859

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Language：English   Publishing type：Research paper (scientific journal)  

More than 20 years have passed since cochlear implantation (CI) was first introduced in Japan. We began CI at the Sapporo Medical University Hospital in 1988; since then, up to the first half of 2015, we have performed CI on 280 ears. In patients aged less than and those aged over 18 years, 121 and 159 ears, respectively, have undergone surgery. This report presents typical cases of CI, such as an adult case, a bilateral case, a case where both hearing and vision were impaired, a pediatric case, a case with multiple handicaps, a case with a genetic mutation leading to severe hearing loss, and a complicated case. In addition, complications with CI cases experienced during extended follow-up periods are also summarized.

DOI： 10.1159/000441858

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The human noggin (NOG) gene is responsible for a broad spectrum of clinical manifestations of NOG-related symphalangism spectrum disorder (NOG-SSD), which include proximal symphalangism, multiple synostoses, stapes ankylosis with broad thumbs (SABTT), tarsal-carpal coalition syndrome, and brachydactyly type B2. Some of these disorders exhibit phenotypes associated with congenital stapes ankylosis. In the present study, we describe a Japanese pedigree with dactylosymphysis and conductive hearing loss due to congenital stapes ankylosis. The range of motion in her elbow joint was also restricted. The family showed multiple clinical features and was diagnosed with SABTT. Sanger sequencing analysis of the NOG gene in the family members revealed a novel heterozygous nonsense mutation (c.397A>T; p.K133*). In the family, the prevalence of dactylosymphysis and hyperopia was 100% while that of stapes ankylosis was less than 100%. Stapes surgery using a CO2 laser led to a significant improvement of the conductive hearing loss. This novel mutation expands our understanding of NOG-SSD from clinical and genetic perspectives.

DOI： 10.1038/hgv.2016.23

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Language：Japanese   Publisher：顎顔面口腔育成研究会  

Ichushi

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Language：Japanese   Publisher：(一社)日本耳科学会  

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J02471&link_issn=&doc_id=20150306240009&doc_link_id=10.11289%2Fotoljpn.25.51&url=https%3A%2F%2Fdoi.org%2F10.11289%2Fotoljpn.25.51&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.amjoto.2014.02.011

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Language：Japanese   Publisher：日本耳鼻咽喉科免疫アレルギー学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2009&ichushi_jid=J01987&link_issn=&doc_id=20091028360002&doc_link_id=%2Fch6menek%2F2009%2F002702%2F023%2F0082-0083%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fch6menek%2F2009%2F002702%2F023%2F0082-0083%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Ichushi

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Language：Japanese   Publisher：耳鼻咽喉科展望会  

Ichushi

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Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本炎症・再生医学会  

Ichushi

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Language：Japanese  

DOI： 10.11453/orltokyo.51.s32

J-GLOBAL

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Language：Japanese   Publisher：(株)北隆館  

Ichushi

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Language：English  

DOI： 10.1016/j.anl.2004.01.003

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