Masako Kitano

Applicability of the cross-culturally modified University of Pennsylvania Smell Identification Test in a Japanese population.

Background The University of Pennsylvania Smell Identification Test (UPSIT) is a popular olfactory function test used throughout the world. In Japan, however, it is not widely used because it is written in English and some of the test odorants are unfamiliar to the Japanese population. Recently, a cross-culturally modified UPSIT was developed. This study was designed to determine if the Japanese version of the UPSIT (UPSIT-J) is effective in Japanese populations. Methods We administered the UPSIT-J to 50 normosmic Japanese subjects and 54 Japanese patients with known olfactory dysfunction. Subjects were also administered the Japanese standard olfactory threshold test (T&T olfactometry), the Odor Stick Identification Test for Japanese (OSIT-J) and i.v. olfactometry (the Alinamin test). Test results from the UPSIT-J and subjects’ opinions were compared with the standard Japanese tests of olfactory function. Results Most subjects reported that the UPSIT-J was easy and interesting compared with OSIT-J and easier and more interesting than the T&T olfactometry and Alinamin test. Identification rates for nine of the UPSIT-J odorants were found to be <80% for normal subjects. UPSIT-J scores correlated with subjects’ self-reported levels of olfactory function (r s = 0.85), OSIT-J score (r s = 0.86), recognition threshold of the T&T olfactometry (r s = 0.80), and Alinamin test results (r s = 0.38 for latency; r s = 0.52 for duration time). Conclusion Although a cultural bias was detected for some test odorants, this study indicates that the UPSIT-J is effective for use in the clinic to assess olfactory function in the Japanese population.

Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells.

HighlightsIL‐33 was upregulated in nasal polyps of eosinophilic chronic rhinosinusitis.IL‐33 increase MUC5AC gene and MUC5AC protein in primary human nasal epithelial cell.IL‐33 induces goblet cell hyperplasia in primary human nasal epithelial cell. Abstract We investigated whether IL‐33 is involved in mucus overproduction and goblet cell hyperplasia in eosinophilic chronic rhinosinusitis (ECRS). IL‐33 mRNA was significantly higher in the eosinophilic CRS group than in the non‐eosinophilic CRS group from human nasal polyps. IL‐33 induced MUC5AC mRNA and MUC5AC protein, and also goblet cell hyperplasia at air liquid interface culture in human nasal epithelial cells. In addition to that, IL‐33 induced MUC5B and FOXA3, and reduces FOXJmRNA. In conclusion, our present study demonstrated that the direct evidence of IL‐33 which lead to increase mucin gene and protein expression, as well as goblet cell hyperplasia. This study provides novel insights into the role of IL‐33 on mucus overproduction in eosinophilic inflammation of human airways.

Effects of Clarithromycin and Dexamethasone on Mucus Production in Isografted Rat Trachea

Objectives: The purpose of this study was to develop an animal model for the study of mucus overproduction and to assess the effect of a 14-membered macrolide antibiotic and a glucocorticoid on lipopolysaccharide (LPS)-induced mucus production. Methods: Tracheas from donor rats were homografted to recipient rats for 4 weeks, and the usefulness of this tracheal homograft model in the study of mucus production was examined. Results: Oral administration of clarithromycin (CAM) to recipient rats for 4 weeks significantly reduced LPS-induced mucus production in the homografted trachea. Dexamethasone administered for 4 weeks also significantly reduced the mucus volume in LPS-treated homografted trachea compared with that in the control rats. The implanted trachea containing control medium was not histologically different from normal trachea. When the medium instilled into the implanted trachea contained 1 µg/ml LPS, the volume and spinability of mucus produced in the tracheal lumen were significantly increased compared to those in the trachea instilled with control medium. Goblet cell metaplasia was also observed in the implanted trachea containing LPS. Conclusions: The present study shows that LPS-administered homografted trachea is a good animal model of chronic hypersecretory diseases of the upper and lower airways. CAM and dexamethasone could be treatment choices in such hypersecretory diseases.

A targeted next-generation sequencing panel reveals novel mutations in Japanese patients with primary ciliary dyskinesia

OBJECTIVE Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The early diagnosis of PCD is important for the prevention of long-term sequelae; however, this is often challenging because of the phenotypic heterogeneity of PCD and difficulty in genetic analysis. The majority of PCD patients in Japan are not diagnosed properly. To diagnose PCD more accurately, we developed a targeted next-generation sequencing (NGS) panel. METHODS We examined 46 patients (age range, 1-64 years; 23 male and 23 female) who were clinically suspected of PCD. First, mutation hotspots in DNAH5 and DNAI1 were sequenced by the Sanger method. Next, exome sequencing was performed in 32 known PCD genes using our novel NGS panel with the Ion Torrent PGM system. Variant annotation was generated by Ion Reporter Version 5.0 (Life Technologies). Mutations found in the panel were validated by Sanger sequencing. RESULTS Disease-causing gene mutations were found in 10 patients from 7 families: DNAH5 in 4 families, and DNAI1, CCDC40, and RSPH4A in 1 family each. Heterozygous mutations were found in 1 patient. The majority of the mutations found in the present analysis were novel. CONCLUSION Japanese PCD patients have novel mutations in cilia-related genes. This targeted NGS panel can identify disease-causing mutations in patients with PCD.

Novel syndrome with conductive hearing loss and congenital glaucoma in three generations.

The objective of this paper was to describe the clinical and otological findings in multiple members of a family with congenital glaucoma, cardiac anomaly, and conductive hearing loss due to ossicular chain anomalies. We performed a retrospective review of the medical charts and otological materials of multiple members of the same family. Congenital glaucoma and hearing loss were inherited by the proband and her daughter, son, and mother, suggesting autosomal dominant inheritance. The son and daughter also showed atrial septal defects. Exploratory tympanotomies revealed anomalies of the long process of the incus in the proband and her daughter, and tympanoplasty improved hearing loss in both patients. This represents the first description of coexisting congenital glaucoma and conductive hearing loss due to ossicular chain anomalies in multiple members of a single family.