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Mammalian outer hair cells (OHCs) are known to respond to acoustical stimulation with elongation and contraction of the cells' cylindrical soma in vivo, and this motility is related to both the protein motors distributed along the OHC plasma membrane and the cytoskeleton beneath it. Therefore, the cytoskeleton seems to play an important role in the motility of the OHC. Recently, an atomic force microscope (AFM) was used to investigate the OHC cytoskeleton under physiological conditions. However, details were not made clear in that study. In this study, the ultrastructure of the cytoskeleton of fixed OHCs of guinea pigs, which were extracted with Triton X-100, was investigated using the AFM. As a result, the cortical cytoskeleton, which is formed by discrete oriented domains, was imaged, and circumferential filaments and cross-links were observed within the domain. Morphological change of the cytoskeleton of the OHC induced by diamide treatment was then examined using the AFM, and reduction of cross-links was observed. The examination indicates that the cortical cytoskeleton comprises circumferential actin filaments and spectrin cross-links.

Two cases of plunging ranula are reported. Treatment consisted of the total removal of the sublingual gland and evacuation of the cystic contents by the intraoral approach. The cyst remained just after the surgery in both cases, but then gradually regressed and disappeared within two months after the surgery. These findings support total removal of the sublingual gland as being the best method of treatment. We believe that complete dissection of the cyst with cervical incision as well as drainage of the cystic contents are unnecessary when the diagnosis of the plunging ranula is confirmed.

As electromotility may arise from a conformational change of the molecules' 'protein motors', which might be distributed along the outer hair cell (OHC) lateral wall, the force generated by the OHC electromotility would be related not only to the conformational change of the protein motors but also to the mechanical properties of the lateral wall. Therefore, a detailed understanding of the mechanical properties of the OHC lateral wall is important. In our previous reports, to understand the difference in the stiffness along the cell axis, the local deformation of the OHC in response to hypotonic stimulation was analyzed by measuring the displacement of microspheres attached randomly to the cell lateral wall, and the distribution of Young's modulus along the cell axis was obtained using the contact mode of an atomic force microscope (AFM). These investigations revealed that the stiffness of the cell in the apical region was greater than that in other regions where the stiffness is constant. In this study, the ultrastructure of the OHC lateral wall was investigated with the oscillation imaging mode of the AFM (Tapping Mode), and the relationship between the stiffness along the cell axis and the ultrastructure that was observed by the AFM imaging was analyzed. From the analysis, it was concluded that the circumferential filaments observed in the tapping mode AFM are actins which are part of the cortical lattice, and that the difference between the intervals of the circumferential filaments in the apical region and those in other regions is one factor that causes the high stiffness in the apical region.

The effect of the ototoxic molecule cisplatin (cis-DDP) on the voltage-dependent Ca2+ channel in dissociated outer hair cells (OHCs) of guinea-pig cochlea was investigated using a whole-cell pathch-clamp technique. Cis-DDP had antagonistic effect on the Ca2+ channel and reversibly suppressed the Ca2+ current in a concentration-dependent manner. These results suggested that one of the ototoxic mechanisms of cis-DDP is involved in the inhibition of the Ca2+ channel in OHCs.

We here report a relatively rare case of traumatic injury of the tympanic membrane caused by a sticky-tipped applicator as well as some characteristics of this sticky-tipped applicator that were examined experimentally. This rare case was very unusual in that the injury was caused by external force applied from the medial to lateral direction during very careful cleaning (no unexpected force). Although removal of cerumen by a sticky substance seems to be an excellent idea, the present case shows that the stickiness that facilitates removal of the cerumen may be dangerous for thin, dry skin such as the tympanic membrane. Actually, the experimental considerations indicated that the stickiness was affected by the surface condition of the objective: soft, dry conditions increase it, while on the contrary, moist, dusty and oily conditions reduce it. The stickiness of the applicator, which was adjusted to use in the ear canal with an oily surface, appeared to be too large for a dry tympanic membrane. It is recommended that the sticky substance should be removed from the tip area or reduced by application of oil or powder before use.

The outer hair cell (OHC) from the organ of Corti plays a crucial role in hearing through its unique voltage-dependent mechanical responses. Furosemide, one of the loop diuretics, disrupts normal cochlear function. Here we report on direct effects of furosemide on OHC motility-related, voltage-dependent capacitance using the whole-cell patch-clamp technique. Extracellularly applied furosemide reversibly shifted the voltage at peak capacitance (V(pkC(m))) to positive levels. The shift, whose maximum approached 90 mV, evidenced a Hill coefficient of 1.5 and K(1/2) of 10 mM. Changes in the magnitude of nonlinear capacitance were not fully reversible. While it is clear that the overwhelming effect of furosemide on hearing results via its effects on the endolymphatic potential, the present results indicate that furosemide directly alters OHC motility and may, in part, contribute to sensory dysfunction.

1. Isolated outer hair cells (OHCs) from the guinea-pig were whole-cell voltage clamped to study the influence of initial voltage on the voltage dependence of motility-related gating current or, equivalently, on the voltage dependence of membrane capacitance. 2. Prepulse delivery caused changes in the magnitude of motility-related gating currents, which are due predominantly to shifts in the voltage at peak capacitance (VpkCmm). Depolarization shifts VpkCm in the hyperpolarizing direction, and hyperpolarization does the opposite. The mean shift between -120 and +40 mV prepulse states with long-term holding potentials (> 2 min) at -80 mV was 14. 67 +/- 0.95 mV (n = 10; mean +/- s.e.m.). 3. The effect of initial membrane potential is sigmoidal, with a voltage dependence of 23 mV per e-fold change in VpkCm, and maximum slope within the physiological range of OHC resting potentials. This indicates that the cell is poised to respond maximally to changes in resting potential. 4. The kinetics of prepulse effects are slow compared with motility-related gating current kinetics. High-resolution measurement of membrane capacitance (Cm) using two voltage sinusoids indicates that shifts in VpkCm induce Cm changes with time courses fitted by two exponentials (tau0, 0.070 +/- 0.003 s; tau1, 1.28 +/- 0.07 s; A0, 1.54 +/- 0.13 pF; A1, 1.51 +/- 0.13 pF; means +/- s.e.m. ; n = 22; step from +50 to -80 mV). Recovery of prepulse effects exhibits a similar time course. 5. Prepulse effects are resistant to intracellular enzymatic digestion, to fast intracellular calcium buffers, and to intracellular pressure. Through modelling, we indicate how the effect may be explained by an intrinsic voltage-induced tension generated by the molecular motors residing in the lateral membrane.

A 43-year-old man with a primary leiomyosarcoma of the left sphenoid sinus is presented. To our knowledge, this is an unusual case of leiomyosarcoma, which has never been reported in the literature. Accurate and safe diagnosis was obtained by an endonasal endoscopic approach with minimal tissue invasion.

Salicylate, one of the most widely used drugs, is known to induce reversible tinnitus and hearing loss. Salicylate interferes with outer hair cells (OHCs), which are believed to underlie normal auditory frequency selectivity and sensitivity. In the present experiments, the effects of salicylate and lanthanides on OHC motility and nonlinear capacitance were investigated by using isolated guinea-pig OHCs while attempting to avoid inadvertent intracellular pressure change, which itself can affect OHC motility and capacitance. Either extracellularly or intracellularly applied salicylate reduced nonlinear peak capacitance (Cmpk) and shifted the voltage at peak capacitance to depolarized levels. Concentration–response curves for reduction inCmpkby salicylate and GdCl3revealed a half-maximal concentration and Hill coefficient of 1.6 mmand 1.0, and 0.6 mmand 1.2, respectively. In comparable groups of OHCs, the normalCmpkvalues of which were near 40 pF, averageCmpkdecreased to 28 and 36 pF for intracellularly and extracellularly applied salicylate, respectively. Salicylate reduced, but did not completely block, the voltage-induced length change. Extracellularly, but not intracellularly, applied lanthanide blocked voltage-induced movement and capacitance almost completely. After intracellular trypsin treatment, salicylate reduced voltage-dependent capacitance reversibly, suggesting that salicylate directly acts on the sensor/motor and not via effects on intracellular structures, such as the subsurface cisternae. The results are consistent with the hypothesis that the dissociated, charged form of salicylate directly interacts with the sensor/motor on the inner aspect of the OHC plasma, whereas lanthanides interact on the outer aspect.

The unique electromotility of the outer hair cell (OHC) is believed to promote sharpening of the passive mechanical vibration of the mammalian basilar membrane. The cell also presents a voltage-dependent capacitance, or equivalently, a nonlinear gating current, which correlates well with its mechanical activity, suggesting that membrane-bound voltage sensor-motor elements control OHC length. We report that the voltage dependence of the gating charge and motility are directly related to membrane stress induced by intracellular pressure. A tracking procedure was devised to continuously monitor the voltage at peak capacitance (VpkCm) after obtaining whole cell voltage clamp configuration. In addition, nonlinear capacitance was more fully evaluated with a stair step voltage protocol. Upon whole cell configuration, VpkCm was typically near -20 mV. Negative patch pipette pressure caused a negative shift in VpkCm, which obtained a limiting value near the normal resting potential of the OHC (approximately -70 mV) at the point of cell collapse. Positive pressure in the pipette caused a positive shift that could reach values greater than 0 mV. Measures of the mechanical activity of the OHC mirrored those of charge movement. Similar membrane-tension dependent peak shifts were observed after the cortical cytoskeletal network was disrupted by intracellular dialysis of trypsin from the patch pipette. We conclude that unlike stretch receptors, which may sense tension through elastic cytoskeletal elements, the OHC motor senses tension directly. Furthermore, since the voltage dependence of the OHC nonlinear capacitance and motility is directly regulated by intracellular turgor pressure, we speculate that modification of intracellular pressure in vivo provides a mechanism for controlling the gain of the mammalian "cochlear amplifier".

Background Hearing impairment is a prevalent and chronic condition in older people. This study investigated the relationship between cognitive function and hearing impairment in a Japanese population. Methods A pure-tone average (0.5-2.0 kHz) was used to evaluate hearing impairment in 846 participants of the Iwaki Health Promotion Project who were aged at least 50 years old (310 men and 536 women). We also administered the Mini-Mental State Examination (MMSE), the Center for Epidemiologic Studies for Depression (CES-D) scale, Starkstein's apathy scale (AS) and the Short Form Health Survey Version 2 (SF-36v2). A multiple linear regression analysis assessed the association between hearing impairment and mental correlates. Results The overall prevalence of hearing impairment in this study population was 37.7%. The participants with hearing impairment were older and less educated compared to those with no hearing problems. We observed significant differences in the MMSE and AS scores between the mild/moderate to severe groups versus the non-impaired group. After adjusting for age, gender and amount of education, hearing impairment was significantly associated with MMSE and AS scores, but not with CES-D scores. Hearing impairment was significantly related to the social functioning (SF) and role emotional (RE) scores of the SF-36v2. Conclusions Hearing impairment is common among older people and is associated with cognitive impairment, apathy and a poor health-related quality of life. Screening for and correcting hearing impairments might improve the quality of life and functional status of older patients.

The effects of various Ca2+ antagonists and aminoglycoside antibiotics on the Ca2+ channel in isolated outer hair cells of the guinea pig were investigated using a whole-cell patch-clamp technique. The inhibitory action was in the order of La3+ much greater than Cd2+ much greater than Ni2+ greater than Co2+ for inorganic Ca2+ antagonists, and flunarizine = nicardipine greater than omega-conotoxin greater than methoxyverapamil = diltiazem much greater than amiloride for organic ones. Aminoglycoside antibiotics also had antagonistic effects on the Ca2+ channel.

A method of designing a digital hearing aid suitable for sensorineural hearing loss with a narrow audible range is proposed. The input signal is divided into short-time blocks (8 ms), and its spectrum is calculated using short-time fast Fourier transforms. The frequency-gain characteristic of the block is determined using the calculated spectrum and loudness compensation functions which describe the relation between the loudness perceived by normal listeners and that perceived by an impaired listener. The input signal within the block is processed by a single digital filter using the calculated gain characteristics. This algorithm is realized using a digital signal processor. The results of monosyllabic speech tests were that the scores of the speech test for the proposed system were improved over a wide range of input levels compared with those for the linear system for nine of 13 sensorineural impaired subjects. >

A method of designing a digital hearing aid for speech signal suitable for sensorineural hearing loss with a narrow audible range is proposed. First, the input signal is divided into short time blocks (8 ms) and its spectrum is analyzed using short‐time FFT. Then the frequency‐gain characteristic of the digital filter for the block is determined using loudness compensation functions that describe the relation between the loudness of normal listeners and that of impaired listeners, so that the input signal within the block is projected on to the dynamic range of the subject. This algorithm is realized using a digital signal processor (DSP). The results of monosyllabic intelligibility tests to evaluate the performance of the system for six sensorineural impaired listeners are also shown. [Work supported by Grant‐in‐Aid for Scientific Research from the Ministry of Education and the Ministry of Public Welfare.]

Periostin is a 90-kDa member of the fasciclin-containing family; it functions as part of matricellular proteins, and its production by airway epithelial cells is induced by IL-4 and IL-13. Periostin is secreted by fibroblasts and upregulated in the airway epithelia of patients with bronchial asthma; it is considered to contribute to remodeling under this pathological condition. However, despite many studies in diverse research areas, our overall understanding of this intriguing molecule is still inadequate. Here, we integrate the available evidence on periostin expression and its roles in otolaryngological diseases, including allergic rhinitis, chronic rhinosinusitis with nasal polyps, aspirin-induced asthma, organized hematoma, eosinophilic otitis media, and IgG4-related disease. Periostin might be involved as an important structural mediator in pathological processes such as insult and injury, Th2-driven inflammation, extracellular matrix restructuring, fibrosclerosis, tumor angiogenesis, and tissue remodeling.

Introduction Granulomatosis with polyangiitis is characterized by systemic inflammation of medium and small blood vessels. Aortic involvement in granulomatosis with polyangiitis is extremely rare. As far as we know this is the first reported case of successful treatment in a patient with granulomatosis with polyangiitis complicated with aortic aneurysm rupture. Case presentation We describe a case of granulomatosis with polyangiitis in a 38-year-old Japanese man who developed an aortic aneurysm rupture 22 years after disease onset. The patient was operated on and a J-graft was inserted. He recovered uneventfully. Conclusion Recommendations in regard to, and consideration of, aortic involvement should be kept in mind in the long-term careful follow up of granulomatosis with polyangiitis.

BackgroundThymidylate synthase (TS) is an important target for chemotherapeutic treatment of cancer and high expression of TS has been associated with poor prognosis or refractory disease in several cancers including colorectal and head and neck cancer. Although TS is known to regulate cell cycles and transcription factors, its potency as a therapeutic target has not been fully explored in adenoid cystic carcinoma (ACC).MethodsAn ACC cell line (ACC3) was transfected with siRNA targeting the TS gene and inhibition of cell growth and induction of apoptosis-associated molecules were evaluatedin vitro. In addition, thein vivoeffect of TS siRNA on tumor progression was assessed using a xenograft model.ResultsOur results demonstrated that ACC3 cells showed significantly higher TS expression than non-cancer cell lines and the induction of TS siRNA led to inhibition of cell proliferation. The effect was associated with an increase in p53, p21, and active caspase-3 and S-phase accumulation. We also found up-regulation of spermidine/spermine N1-acetyltransferase (SSAT), a polyamine metabolic enzyme. Furthermore, treatment with TS siRNA delivered by atelocollagen showed a significant cytostatic effect through the induction of apoptosis in a xenograft model.ConclusionTS may be an important therapeutic target and siRNA targeting TS may be of potential therapeutic value in ACC.

Background Salivary gland carcinomas are relatively uncommon heterogeneous malignancies characterized by locoregional invasion and distant metastasis. Topoisomerase IIα (topoIIα), located at chromosome 17q21-22, is considered a major mediator of cell proliferation and DNA replication. The purpose of this study was to evaluate the expression of topoIIα in various types of salivary gland tumors and its biological significance. Methods The protein expression of topoIIα was evaluated immunohistochemically in formalin-fixed, paraffin-embedded tissue from 54 salivary gland carcinomas and 20 benign tumors (10 pleomorphic adenomas and 10 Warthin's tumors). The primary salivary gland carcinoma specimens consisted of 17 adenoid cystic carcinomas, 7 adenocarcinomas not otherwise specified, 7 mucoepidermoid carcinomas, 6 salivary duct carcinomas, 3 acinic cell carcinomas, 3 carcinomas ex pleomorphic adenomas, 3 epithelial-myoepithelial carcinomas, 2 carcinosarcomas, 2 lymphoepithelial carcinomas, 2 myoepithelial carcinomas, 1 oncocytic carcinoma, and 1 squamous cell carcinoma. The associations between clinicopathological factors and outcome were analyzed. Results Of the 54 primary salivary gland carcinomas, 38 (70%) showed positive expression (≥10%) of topoIIα protein, and 16 carcinomas (30%) and all benign tumors were negative (p < 0.001). Expression of topoIIα was more frequently observed in salivary duct carcinoma, carcinoma ex pleomorphic adenoma, adenocarcinoma, and adenoid cystic carcinoma, solid type, and it was associated with advanced stage and shortened survival. Conclusion The results of the present study suggest that topoIIα expression is associated with histologically aggressive subtypes and shortened survival. Furthermore, it may provide useful prognostic information and suggests the potential efficacy of topoIIα-targeting therapy in patients with salivary gland carcinoma.