Toshimitsu Kobayashi

Potassium ion recycling pathway via gap junction systems in the mammalian cochlea and its interruption in hereditary nonsyndromic deafness.

In the mammalian cochlea, there are two independent gap junction systems, the epithelial cell gap junction system and the connective tissue cell gap junction system. Thus far, four different connexin molecules, including connexin 26, 30, 31, and 43, have been reported in the cochlea. The two networks of gap junctions form the route by which K+ ions that pass through the sensory cells during mechanosensory transduction can be recycled back to the endolymphatic space, from which they reenter the sensory cells. Activation of hair cells by acoustic stimuli induces influx of K+ ions from the endolymph to sensory hair cells. These K+ ions are released basolaterally to the extracellular space of the organ of Corti, from which they enter the cochlear supporting cells. Once inside the supporting cells they move via the epithelial cell gap junction system laterally to the lower part of the spiral ligament. The K+ ions are released into the extracellular space of the spiral ligament by root cells and taken up by type II fibrocytes. This uptake incorporates K+ into the connective tissue gap junction system. Within this system, the K+ ions pass through the tight junctional barrier of the stria vascularis and are released within the intrastrial extracellular space. The marginal cells of the stria vascularis then take up K+ and return it to the endolymphatic space, where it can be used again in sensory transduction. It is highly probable that mutations of connexin genes that result in human nonsyndromic deafness cause dysfunction of cochlear gap junctions and thereby interrupt K+ ion recirculation pathways. In addition to connexin mutations, other conditions may disrupt gap junctions within the ear. For example, mice with a functionally significant mutation of Brain-4, which is expressed in the connective tissue cells within the cochlea, show marked depression of the endolymphatic potential and profound sensorineural hearing loss. It seems likely that disruption of connective tissue cells by this mutation disrupts K+ ion entry into the stria vascularis and thereby results in loss of endolymphatic potential. The association of sensorineural hearing loss with these genetic disorders provides strong evidence for the necessity of gap junction systems for the normal functioning of the cochlea.

Prognosis of sudden deafness with special reference to risk factors of microvascular pathology.

OBJECTIVE We attempted to elucidate the contribution of microvascular disorders as risk factors to the prognostic outcome in well-defined patients with sudden deafness. METHODS One-hundred and thirty-two patients diagnosed as unilateral sudden deafness were retrospectively analyzed. Auditory function was determined by pure-tone audiometry. Diabetes, hyperlipidemia, and hypertension were considered as microvascular diseases. RESULTS Concurrent microvascular diseases were recognized in 38 patients. Although the hearing disturbance at the first visit showed no difference from patients without concurrent diseases, a better outcome of hearing was obtained in patients without the concurrent diseases. CONCLUSION The poor prognosis observed in patients with the concurrent diseases is likely to have been brought about by preexisting microvascular disease of the hearing organ, which is highly affected by aging.

Effects of various decalcification protocols on detection of DNA strand breaks by terminal dUTP nick end labelling.

To analyse DNA strand breaks by terminal deoxy(d)-UTP nick-end labelling (TUNEL) in calcified tissues including bones and teeth, it is important to decalcify the tissues first. However, the effects of decalcifying reagents on the integrity of DNA are largely unknown. In the present study, we evaluated the usefulness of various decalcifying reagents including 10% EDTA (pH 7.4), 5% trichloroacetic acid (TCA), 5% formic acid, 5% HCl, 10% nitric acid, Plank–Rychlos solution, Morses solution and K-CX solution in TUNEL staining. Mouse maxilla was selected as the experimental system. Apoptotic cells naturally occurring in the epithelium were analysed. Tissues were assessed by soft X-ray imaging to confirm complete decalcification. The time required for decalcification of the tissue was 7 days with 10% EDTA and 2 days with other decalcifiers. Decalcified tissues were stained with Methyl/Green–Pyronine Y or 4′, 6-diamidino-2-phenylindole for assessment of DNA integrity. Nuclei of epithelial cells were strongly positive for both dyes after decalcification with 10% EDTA, 5% TCA, Morses solution and 5% formic acid. The other reagents failed to retain DNA. Our results demonstrated good TUNEL staining of the maxilla treated with 10% EDTA or 5% TCA . Based on the required time for processing and the signal-noise ratio, we recommend 5% TCA as the decalcifying reagent to analyse for DNA strand breaks.

Measurement of guinea pig basilar membrane using computer-aided three-dimensional reconstruction system.

Cochleas are known to have the ability to analyze a frequency widely, and this ability seems to be owed mostly to the basilar membrane (BM) configuration. However, the relationship between the cochlear frequency-position map and the BM configuration is not clear. Therefore, in this paper, the internal structures of a guinea pig cochlea, especially the BM configuration, were reconstructed and measured using a computer-aided three-dimensional (3-D) reconstruction system. Then, an attempt was made to examine the influence of the BM configuration on the cochlear frequency-position map. The measurement results indicate that the width of the BM increased and its thickness decreased with an increase in the distance from the basal turn towards the apical turn. Theoretical consideration reveals that the wide frequency-position of the cochlea is achieved by not only the BM configuration change along the length of the cochlea but also the change of the Youngs modulus of the BM along the length of the cochlea.

Measurement of Endocochlear DC Potentials in Ears with Acoustic Neuromas: A Preliminary Report

The pathogenesis of hearing loss in acoustic neuromas remains to be elucidated. To obtain more detailed information about inner ear damage in this disease, especially that dealing with the possibility of ischemia of the inner ear due to compression of the blood supply in the internal auditory canal by acoustic neuromas, measurement of endocochlear DC potential (EP) was attempted in three ears with acoustic neuromas during surgical removal of the tumors by the translabyrinthine approach. The size of each tumor was 3.0, 0.8, and 1.8 cm, respectively. An EP with a positive value was recorded in each of the three ears, i.e., 54, 57, and 38 mV, respectively, although the first and third patients were profoundly deaf on the side with a tumor. These findings were interpreted as being evidence of retention of function by the stria vascularis and the existence of blood supply to the inner ear in spite of the presence of tumors. Measurement of the EP seems to provide a new tool with which to analyze the causes of hearing loss in acoustic neuromas. Relatively low EP values may suggest mild dysfunction of the stria vascularis with acoustic neuromas.

Superficial Siderosis of the Central Nervous System

This is a case of superficial siderosis of the central nervous system (SSCN). The diagnosis of SSCN was based on the result of T2-weighted magnetic resonance imaging and on suggestive clinical manifestations. The pure-tone audiogram showed bilateral progressive sensorineural hearing loss with a poor speech discrimination score and Jerger type IV. The remarkable elevation of the detective threshold of cochlear microphonics on electrocochleography was found and distortion product otoacoustic emission (DPOAE) showed no response: These electrophysiologic examinations, including electrocochleography and DPOAE, revealed that the progressive sensorineural hearing loss in this case was caused by both retrocochlear and cochlear damages.

A case of bilateral middle-ear squamous cell carcinoma

Only eight cases of bilateral middle-ear squamous cell carcinoma (SCC) have been reported to date. We present the case of a 75-year-old male with bilateral middle-ear SCC and review the previously reported cases. The patient was diagnosed as having moderately-differentiated SCC in the left middle ear in February 1995 and well-differentiated SCC in the right middle ear in September 1997. He initially received radiation therapy with (60)Co pendulum (64 Gy) in the left ear and was subsequently treated by Liniac irradiation (50 Gy) in the right ear. He has now been followed up at our ENT clinic for 29 months without vertigo or facial nerve palsy since the second radiation therapy. Although he has a residual tumour in the right middle ear invading the middle cranial fossa dura, no sign of recurrence has been detected in the left ear.

Effect of Ethacrynic Acid upon the Peripheral Vestibular Nystagmus

The effect of ethacrynic acid (ETA) upon pendular rotation nystagmus and paralytic nystagmus was examined using 61 guinea pigs. 100 mg/kg ETA reduced these nystagmus but 30 mg/kg ETA had on effect. Galvanic nystagmus, Bechterews compensatory nystagmus, OKN and EEG were not affected by 100 ng/kg ETA. These results are highly suggestive that the inhibition of the peripheral vestibular nystagmus by ETA is mainly due to the reduction of the ampullar endolymphatic potential.

Contents Vol. 71, 2009

R.L. Alford, Houston, Tex. M. Anniko, Uppsala D.D. Backous, Seattle, Wash. Y.A. Bayazit, Ankara H.H. Birdsall, Houston, Tex. P.J. Bradley, Nottingham J. Califano, Baltimore, Md. P.F. Castellanos, Bimingham, Ala. C. Cernea, São Paulo F.-L. Chi, Shanghai A. Chiu, Philadelphia, Pa. N. Cohen, Philadelphia, Pa. M.D. Eisen, Hartford, Conn. E. Ferekidis, Athens A. Ferlito, Udine R.L. Ferris, Pittsburgh, Pa. L.L. Gleich, Cincinnati, Ohio D.-M. Han, Beijing J.P. Harris, San Diego, Calif. R. Häusler, Bern I. Hochmair, Innsbruck K. Hörmann, Mannheim W. Hosemann, Greifswald K.-B. Hüttenbrink, Köln S. Iurato, Bari A. Kakigi, Tokyo B.N. Landis, Geneva T. Linder, Luzern W.J. Mann, Mainz J.J. Manni, Maastricht J.B. Nadol, Jr., Boston, Mass. J.N. Palmer, Philadelphia, Pa. G.J. Petruzzelli, Chicago, Ill. R. Probst, Zürich A. Rinaldo, Udine R.J. Ruben, Bronx, N.Y. I. Salahuddin, Karachi A. Schrott-Fischer, Innsbruck A. Shiotani, Saitama G.A. Tavartkiladze, Moscow T.N. Teknos, Columbus, Ohio K. Tomoda, Osaka R.P. Tufano, Baltimore, Md. R.T. Younis, Miami, Fla. P. Zbären, Bern Journal for Oto-Rhino-Laryngology, Head and Neck Sugery