Mitsuyoshi Nagura

Ultrastructural localization of megalin in the rat cochlear duct.

Megalin is an endocytic receptor predominantly expressed in the kidney proximal tubule cells. In the present study, localization of megalin was examined using a post-embedding immunogold method in the rat cochlear duct. Marginal cells of the stria vascularis were labeled on the apical surface, but not on the basolateral surface. This localization pattern resembles kidney proximal tubule cells. Immunoreactivity was also detected on various other cells, including epithelial cells of the spiral prominence and epithelial cells of Reissners membrane. In contrast, virtually no gold particles were seen on intermediate cells and basal cells of the stria vascularis, mesothelial cells of Reissners membrane or fibrocytes in the lateral wall. Also unlabeled were cells in the tympanic wall of the cochlear duct, including sensory cells and supporting cells of the organ of Corti. The present findings show the involvement of megalin in endocytosis of marginal cells and are suggestive of different uptake mechanisms for aminoglycosides in the kidney proximal tubule cells and in the cochlear sensory cells.

Effects of corticosteroid, contrast medium and ATP on focal microcirculatory disorders of the cochlea.

We evaluated the ability of various drugs to prevent the decrease in focal cochlear blood flow induced by photochemical reaction and investigated the mechanisms underlying this decrease. By means of a photochemical reaction, which produces reactive oxygen species, focal lesions measuring about 1 mm in diameter were induced in the lateral wall of the guinea pig cochlea. The protective effects of hydrocortisone, amidotrizoate and ATP on cochlear blood flow and cochlear vascular conductance changes were evaluated by using a non-contact laser flowmeter. Cochlear blood flow and cochlear vascular conductance were decreased to 65.1+/-4.9% (mean +/- S.E.M.) and 57.0+/-3.7% (mean +/- S.E.M.) of the initial level 30 min after the start of the photochemical reaction, respectively. Hydrocortisone significantly prevented the decline in the cochlear blood flow and cochlear vascular conductance and reduced the area of stria vascularis degeneration in a dose-dependent manner. Neither amidotrizoate nor ATP significantly prevented the decrease in cochlear blood flow or cochlear vascular conductance. Hydrocortisone was more effective than vasodilators or other agents which increase cochlear blood flow in preventing the photochemically induced decrease in cochlear blood flow. This might be due to the antioxidative effects of hydrocortisone.

Role of nitric oxide in focal microcirculation disorder of guinea pig cochlea

This study was designed to evaluate the role of endogenous nitric oxide (NO) in focal microcirculation disorder of the guinea pig cochlea. Focal microcirculation disorder was induced by a photochemical reaction at the lateral wall of the second cochlear turn. Saline or N omega-nitro-L-arginine methyl ester (L-NAME) was administered before the onset of photochemical reaction. Cochlear blood flow (CBF) was measured at the focal lesion (ischemic core), 1 mm from the lesion in the apical and basal direction (ischemic border zone) by using a novel non-contact laser blood flowmeter. NO synthase activities were measured by radioenzymeassay. In the saline pretreatment group, CBF was significantly decreased to 58.8+/-4.4% of the baseline at the ischemic core 30 min after the onset of photochemical reaction (P<0.01), while CBF showed no significant change at the ischemic border zone. In the L-NAME pretreatment group, CBF was significantly decreased not only at the focal lesion (48.3+/-6.5%, P<0.01), but also at the ischemic border zone (apical, 49.3+/-2.3%, P<0.05; basal, 58.7+/-7.1%, P<0.05, respectively). NO synthase III activity of cochlea was increased significantly (P<0.01) 15 min after microcirculation disorder. These findings suggest that formation of endogenous NO plays a key role in the maintenance of CBF in acute focal cochlear microcirculation disorder.

Focal Damage to Cochlear Microcirculation Measured using a Non-Contact Laser Blood Flowmeter in Guinea Pigs

The focal microcirculation damage induced by a photochemical reaction in the stria vascularis (SV) of the guinea pig cochlea was evaluated using a non-contact laser blood flowmeter (NCLBF) and the endocochlear potential (EP). Focal degeneration, including vascular thrombosis in the SV produced by the systemic infusion of rose bengal, and the illumination of green light in the second cochlear turn were observed with scanning and transmission electron microscopy. The NCLBF probe was placed at a position 10 mm from the cochlear surface, and the diameter of the laser light was focused to 1 mm in the green light illumination area. The change in NCLBF values induced by the loading of anoxia and administration of epinephrine agreed very well with those obtained with a conventional contact-type laser Doppler flowmeter. Significant decreases in the cochlear blood flow (CBF) (p < 0.01) and EP (p < 0.01) were observed at the site of the photochemical injury compared with the values at the non-illuminated area. CBF gradually decreased (82.0+/-7.3% at 10 min, 71.2+/-5.5% at 20 min, 64.3+/-11.2% at 30 min from the baseline, n=7), but blood pressure was stable. The EP values also decreased gradually during the first 13 min (79.9+/-3.7 mV at pre-illumination, 11.4+/-10.7 mV at 13 min, n=7). The gradual decline in the EP was comparable to the changes in the CBF. The NCLBF was useful for evaluating the haemodynamic properties of the cochlear microcirculation disorders, and this animal model is expected to be suitable for studying the pathology of focal cochlear vascular disease.

Contribution of speech rate to speech perception in multichannel cochlear implant users.

This study describes the effect of speech rate (fast, 11 syllables per second; medium, 9 syllables per second; slow, 6 syllables per second) on speech perception in 10 cochlear implant users. The speech perception performance was evaluated on the basis of the percentage score of syllables that were correctly recalled in sentences composed of 4 to 6 words. The percentage scores at the fast, medium, and slow speech rates were 15.7%, 39.0%, and 56.0%, respectively. The effect of speech rate slowing was significant (p < .0001). Variations in the effect of speech rate slowing were observed in the cochlear implant users. The improvement of speech perception by speech rate slowing was significantly (p < .005) related to the word test score and the score at the fast speech rate. The results reveal that the rate of speech is an important factor in improving the speech perception of cochlear implant users.

Endocochlear potential in focal lesions of the guinea pig cochlea

To estimate the correlation between the cochlear lateral wall and endocochlear potential (EP), the EP was measured at different time intervals up to 3 weeks at cochlear focal lesions made in the guinea pig. Lesions were produced by a photochemical reaction between systemically administered Rose Bengal and green light illumination in the second cochlear turn. Focal strial lesions (mean diameter 975 microm) became apparent under a scanning electron microscope 60 min after illumination, and degeneration of the organ of Corti was recognized at 3 days. The EP was measured continuously for 1 h following onset of the reaction in eight ears. In the other ears, EP measurements were done after various intervals of time up to 3 weeks. The EP showed two declines from pre-illumination level. The first started soon after illumination, reached a minimum value at 25 min, and then slightly recovered by 1 h. The second decline appeared at 3 days after illumination. In contrast to evident focal morphological degeneration 2 weeks post illumination, the EP values had recovered to almost normal. We suggest that the sequential changes in the EP were produced depending on the degeneration and then repairing processes of the endolymphatic boundary tissues.

Efficacy of Onon (pranlukast hydrate) for theImprovement of Quality of Life in Patients with Allergic Rhinitis

The aim of this study was to evaluate the effects of novel leukotriene antagonist, pranlukast hydrate on improvement of quality of life (QOL) as well as reduction of clinical symptoms in patients with allergic rhinitis.Fifty patients with perennial and/or seasonal allergic rhinitis were administered 450mg pranlukast hydrate daily for at least 4 weeks. The severity of clinical symptoms and QOL were assessed before and after treatment.After a 4-week period of treatment, the QOL score significantly improved from 2.1±1.5 to 1.2±1.7 (P<0.0001). In addition, the treatment itself did not affect the QOL of the patients. The severity of symptoms was also significantly reduced (P<0.001). The improvement rates were 66.0% (sneezing), 72.0% (rhinorrea), and 82.0% (nasal obstruction).In conclusion, pranlukast hydrate improves QOL and reduces symptoms in patients with allergic rhinitis.

Prevalence of Hearing Impairment in Retinitis Pigmentosa Population

Abstract Objectives: Sensorineural hearing loss (SNHL) is the most common disease associated with systemic retinitis pigmentosa (RP). Usher syndrome (USH) is a major autosomal recessive disorder characterized by bilateral SNHL and visual impairment caused by RP. USH constituted 43% of systemic RP. Prevalence of USH varies and ranges from 3.5 to 6.2 per 100,000. We conducted a nationwide survey of hearing impairment associated with RP to estimate the prevalence of hearing loss, onset of hearing impairment and proportions of the progressive hearing impairment and vestibular disturbance. Methods: The epidemiological data were derived from questionnaire study on those subjects who were membership registers of the Japanese Retinitis Pigmentosa Society (n = 3200). The questionnaire comprised 10 questions for investigating hearing impairment-related problems such as onset of hearing impairment, awareness of tinnitus or vestibular disturbance or progressive hearing impairment, and history of audiological examination and hearing aid. Results: A total of 834 questionnaires were returned (26.1% response rate) and were analyzed by 828 (25.9%) subjects, who were diagnosed by an ophthalmologist as RP. The prevalence of hearing impairment or tinnitus was 29.5% (n = 244) and 30.4% (n = 252), respectively. The prevalence of cochlear symptom was 42.8% (n = 346). Mean age of hearing impairment onset was 39.2 years. 72.5% of the 244 subjects with hearing impairment had history of audiological examination. The hearing-aid users were 57 subjects (23.4%). Progressive hearing impairment, tinnitus, or vestibular disturbance was experienced in 46.2%, 43.4%, and 58.1%, respectively. Conclusion: The prevalence of hearing impairment in PR population was high and the clinical features were various.

Long-term audiological feature in pendred syndrome caused by SLC26A4 mutation

Abstract Objectives: Pendred syndrome is inherited as an autosomal recessive form and may account for 10% of hereditary hearing loss. It is likely that there is a great variation in hearing loss. We report a case of Pendred syndrome in which a mutation in SLC26A4 gene was detected and show the characteristics of long-term audiological changes. Methods: A 27-year-old woman was followed since March 1979 at Hamamatsu University School of Medicine. She first experienced vertigo at the age of 1 1/2 years and her parents were concerned about her poor response to sound. Mild hearing loss was diagnosed in another clinic at the age of 4 years. Results: Long-term audiological observation over 20 years showed that a 45 dB in the right ear and 41.2 dB in the left ear increased as the average threshold with fluctuation and marked progression combined with vertigo occurred before the age of 12. After that, the threshold moved to the stable. The audiogram indicated an asymmetric pattern and sensorineural hearing loss predominantly. A caloric test revealed a normal response on both sides. Corticosteroids were not effective in improving hearing loss. A diffuse goiter was noticed at the age of 15 years. The goiter slightly enlarged over the 12 years follow-up period. Conclusion: Although the His723Arg missense mutation is a change at unconserved position in the pendrin protein, it is a pathological mutation in our case because it was found in the homozygous state. It is possible that different mutations within the same gene lead to different phenotypes.

A model of two-stage newborn hearing screening with automated auditory brainstem response

Our purpose was to evaluate a two-stage newborn hearing screening program using automated auditory brainstem response (AABR) before discharge and to describe our follow-up program. This study used 4085 infants born in the Seirei-Hamamatsu and Mikatahara General Hospitals during a 2-year period. The initial screening test was performed 2 or 3 days after birth at an intensity of 35 dBnHL. For the infants who were referred from this test, the re-screening test was performed 5 or 6 days after birth. Diagnostic work-up with auditory brainstem response (ABR), otoacoustic emissions (OAE), and a conditioned orientation reflex audiometry (COR) test were performed by the age of 3-6 months. The referral rate was 1.20% (49/4085 infants) in the first test and 0.71% (29/4085 infants) in the two-stage screening. The two-stage screening procedure was able to reduce the false-positive rate from 0.83 to 0.34%. The incidence of bilateral and unilateral congenital hearing loss diagnosed by ABR was 8/4085 (0.20%) infants and 7/4085 (0.17%) infants, respectively. One infant with congenital cytomegalovirus infection, who passed the two-stage AABR tests, was diagnosed with hearing loss 1 month after birth, using ABR. The two-stage measurement of AABR is effective and time efficient due to significant decreases in the referral rate and the false-positive rate.