Narihisa Ueda

Mitochondrial DNA deletion is a predisposing cause for sensorineural hearing loss

Composed of a postmitotic stable tissue, the inner ear is a target organ for mitochondrial DNA (mtDNA) mutation. To determine whether mtDNA mutation is a predisposing factor in patients with sensorineural hearing loss (SNHL), the authors assessed the mtDNA4977 deletion from 60 patients with SNHL and 47 normal control subjects. All cases had no past history of ototoxic or noise exposure, middle ear disease, or other known etiological factors for SNHL. DNA specimens extracted from peripheral blood leukocytes were used for detection of mtDNA4977 deletion by polymerase chain reaction. Patients with SNHL had a significantly higher rate of the mtDNA4977 deletion than did controls (75% vs. 30%, P < 0.0001). The detection rate of mtDNA4977 deletion was significantly increased with the deterioration of the hearing threshold. Aging did not influence the detection rate of mtDNA4977 deletion in either the control or SNHL group. The authors have described high detection rates of the mtDNA4977 deletion in patients with idiopathic bilateral SNHL and propose that at least some of the advanced SNHL cases should be categorized as mitochondrial oxidative phosphorylation diseases. This inference would offer novel possibilities for treatment and prevention of SNHL including presbycusis.

Bilateral Sensorineural Hearing Loss Associated With the Point Mutation in Mitochondrial Genome

Mitochondrial DNA (mtDNA) mutation associated with sensorineural hearing loss (SNHL) has previously been described in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes) and in aminoglycoside‐induced deafness. The authors of this study report three cases of SNHL associated with mtDNA mutation (3243A→G). They examined the clinical features of this type of SNHL by audiologic studies and examined the mtDNA mutation by the polymerase chain reaction technique.

Expression and localization of the Na-K-2Cl cotransporter in the rat cochlea.

We identified the localization of the basolateral bumetanide-sensitive Na-K-2Cl cotransporter (BSC2) in the cochlea using an in situ hybridization method. In the rat cochlea, the BSC2 mRNA was mainly expressed in the strial marginal cells. Although the fibrocytes localized at the spiral prominence showed a weak expression of BSC2 mRNA, no expression was observed in the organ of Corti or spiral ganglion cells. The present findings are well consistent with a proposed cell model of ion transport in the marginal cell.

Relationships Among Nasal Obstruction, Daytime Sleepiness, and Quality of Life

Objectives: There has been growing awareness that nasal obstruction may impair various daily and social activities. We performed a questionnaire survey on a working population to clarify the relationships among nasal obstruction, daytime sleepiness, and quality of life (QOL).

Chronic nasal obstruction causes daytime sleepiness and decreased quality of life even in the absence of snoring.

Background There has been a growing awareness that nasal obstruction may impair various daily and social activities. We performed a questionnaire survey in a working population to clarify the contribution made by snoring concomitant with nasal obstruction to daytime sleepiness and quality of life (QOL). Methods Seven thousand nine hundred eighty daytime workers were asked to complete questionnaires, 7702 responded, and the data from 3442 subjects were finally analyzed. Nasal obstruction and snoring were graded into three and four categories, respectively. Daytime sleepiness and QOL were assessed by the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey, respectively. Results Subjects with chronic nasal obstruction, even if snoring was absent, reported significantly higher ESS scores and lower QOL scores than control subjects, and the presence of habitual snoring had an additive influence on these changes. The ESS and mental QOL scores adjusted for age, sex, and body mass index showed the same tendency. Conclusion Induction of sleep-disordered breathing (SDB) is a possible cause of excessive daytime sleepiness and impaired QOL in subjects with nasal obstruction. A variant of SDB such as silent upper respiratory resistance syndrome may participate in this phenomenon in the absence of snoring.

Hearing Loss With a Mitochondrial Gene Mutation Is Highly Prevalent in Japan

Objectives/Hypothesis: Mutations in the mitochondrial genome may predispose people to sensorineural hearing loss. An adenine to guanine point mutation in the tRNALeu(UUR) gene at nucleotide 3,243 is one of the deaf‐related mutations. This mutation is reported to be associated with 0.9% of diabetes mellitus patients. However, the prevalence of this mutation in hearing‐impaired patients still remains unknown. The aim of this study was to determine the prevalence of this mutation among bilaterally sensorineural hearing‐impaired patients in Japan. Study Design: Retrospective survey of 100 patients with bilateral sensorineural hearing loss without any evident causes. Methods: Mitochondrial DNA fragments from the patients were amplified by polymerase chain reaction, followed by a restriction enzyme fragment length polymorphism method. Results: Three patients with this mutation were identified. Their clinical profiles were different from the category which had been considered as hearing loss caused by this mitochondrial gene mutation. Conclusions: The mutation is associated with approximately 3% of bilateral sensorineural hearing loss cases of unknown origin and is possibly distributed widely in sensorineural hearing‐impaired patients in Japan.

Relationships between nasal obstruction, observed apnea, and daytime sleepiness.

Objective We administered a questionnaire survey to a working population in an attempt to clarify the relationships between self-reported nasal obstruction, observed apnea during sleep, and daytime sleepiness. Study Design A total of 7980 daytime workers were asked to complete questionnaires about nasal obstruction, apnea during sleep, and daytime sleepiness. Of the 7702 responses, the data from 4818 subjects were analyzed. Nasal obstruction and observed apnea were graded into 3 categories. Daytime sleepiness was assessed by the Epworth Sleepiness Scale. Results Subjects with chronic nasal obstruction had 5.22 and 2.17 times higher odds for having habitual observed apnea and excessive daytime sleepiness (EDS), respectively, compared with those without nasal obstruction (P < 0.001). After adjusting for 3 potential confounding factors (age, sex, and body mass index) and the presence of habitual observed apnea, odds ratios for having EDS decreased, but still remained significant. Conclusion Nasal obstruction is likely to cause daytime sleepiness, at least in part, by causing sleep-disordered breathing including apnea during sleep.

Subcellular distribution of protein kinase C in the living outer hair cell of the guinea pig cochlea

Immunohistochemical staining using isoform-specific antibodies and intracellular localization using fluorescent probes for protein kinase C (PKC) were evaluated in the cochlear outer hair cell (OHC). Among three isoforms of classic PKC, PKC alpha was selectively stained in the fixed OHC as well as inner hair cells under a surface preparation method. Two types of fluorescent probes to detect subcellular localization of PKC were observed with a confocal laser scanning microscopy in the present study, fim-1 diacetate which binds to the ATP-competitive catalytic domain of PKC and Bodipy FL C12-phorbol acetate which binds to specific site localized to the first cysteine-rich loop of the C1 region in the regulatory domain. High fluorescence intensity of both dyes was observed in subcuticular and subsynaptic regions, infracuticular network, and along the lateral wall. The displacement experiments to evaluate binding specificity were performed by incubating Bodipy FL C12-phorbol acetate in the presence of 10 microM phorbol 12-myritate 13-acetate (PMA) and the fluorescence was totally disappeared. For the acute treatment of phorbol ester, cells were preincubated with 1 microM PMA 30 min before loading with fim-1 diacetate. The brightest area in the plasma membrane became much larger as compared with untreated cells, which suggests a dramatic translocation of PKC to the plasma membrane. The biological functions involving PKC in the OHC are discussed.

Clinical evaluation of a portable digital hearing aid with narrow-band loudness compensation.

A new portable digital hearing aid referred to as CLAIDHA (Compensate for Loudness by Analyzing Input-signal Digital Hearing Aid), which employs frequency-dependent amplitude compression based on narrow-band loudness compensation, was clinically evaluated in 159 subjects with hearing loss. The results of speech tests revealed better intelligibility compared with the subjects own hearing aids; the advantage of using CLAIDHA in daily life was also indicated by the results of a questionnaire completed by the subjects. In about 64% of the subjects with a flat, gradually sloping type of hearing loss, CLAIDHA was satisfactorily adopted for daily use. However, in the subjects with a steeply sloping type of hearing loss and subjects with losses mainly at high and low frequencies, with near-normal mid-frequency hearing. this loudness compensation scheme seems to be slightly less effective.

Subcellular Distribution and Pharmacological Identification of M1 Receptors in the Submucosal Nasal Gland Acinar Cells of Guinea Pigs

A muscarinic receptor in the submucosal nasal gland acinar cells controls electrolyte and fluid secretion. We investigated the pharmacological identification and the subcellular distribution of Ml receptor using a selective antagonist, pirenzepine (PZ). Intracellular Ca2+ concentration ([Ca2+]i) in the isolated acinar cells was measured by a fura-2 method. Addition of PZ inhibited the increase of the [Ca2+]i induced by acetylcholine in a dose-dependent manner, indicating the presence of the Ml receptor. Both fixed section of the nasal septal mucosa and living isolated acinar cells were selectively stained by fluorescence-labeled PZ. Furthermore, confocal laser scanning microscopy revealed that PZ specifically labeled the plasma membrane in the isolated acinar cells. Thus, M1 receptor was proven to be located in the plasma membrane of the submucosal nasal gland acinar cell.