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Biomedical subjects

Keiji Tabuchi

Publications and source records attributed to Keiji Tabuchi.

At least 19 recordsLinked to original sources
PubMed2026

Hearing loss associated with CDC42 in mice and humans (Takenouchi-Kosaki syndrome): CDC42 and RHOQ synergistically function in cochlear hair cells.

CDC42 is involved in multiple signaling pathways, including actin organization and polarity. We previously reported progressive sensorineural hearing loss (SNHL) in inner ear hair cell (HC)-specific Cdc42-knockout (Atoh1-Cre+/-;Cdc42flox/flox) mice. However, the phenotype was milder than expected, suggesting possible redundancy with other Rho-family GTPases. Thereafter, Takenouchi-Kosaki syndrome (TKS), caused by de novo CDC42 mutations and manifesting as SNHL, was reported, in which the p.Y64C mutation was speculated to be constitutively active. However, the relationship between CDC42 status and hearing phenotypes in TKS remains unclear. Using cell models, mouse models, and patient data, we propose that impaired and/or dysregulated cycling between GDP/inactive and GTP/active forms, through either loss-of-function or constitutive activation, can lead to SNHL. Furthermore, to test redundancy, we generated HC-specific Cdc42;RhoQ double-knockout (Atoh1-Cre+/-;Cdc42flox/flox;RhoQflox/flox) mice, which revealed synergistic roles of CDC42 and RHOQ in cochlear HCs. Supporting this synergy, MDCK cells with CDC42 and RHOQ double knockdown showed greater phospho-cofilin, a key regulator of actin turnover, elevation than single knockdowns.

CDC42↗
PubMed2006

Basaloid squamous cell carcinoma of the maxillary sinus: a report of two cases.

Basaloid squamous cell carcinoma (BSCC) is a highly aggressive neoplasm and a histologically distinctive variant of squamous cell carcinoma. Since the first description by Wain et al. in 1986, only 18 cases with BSCC in the nasal cavity or in the paranasal cavity have been reported in the English literature. We report herein two cases of BSCC of the maxillary sinus. Case 1 was 78-year-old man, who received preoperative radiotherapy and operation. He was alive without disease for 25 months after the operation. Case 2 was a 60-year-old man who received radiotherapy without operation. He died of lung metastasis 6 months after the initial diagnosis. We reviewed the clinical features of BSCC from the literature.

Aged↗
PubMed2006

The effects of the glucocorticoid receptor antagonist RU486 and phospholipase A2 inhibitor quinacrine on acoustic injury of the mouse cochlea.

Glucocorticoids are used clinically for the treatment of acoustic injury. However, the protective mechanism of glucocorticoid in acoustic injury has not been completely clarified. Also, the effects of phospholipase A2 (PLA2) on acoustic injury have not been examined to the best of our knowledge. The purpose of the present study was to examine the effects of methylprednisolone, a glucocorticoid receptor inhibitor (RU486) and a phospholipase A2 inhibitor (quinacrine) on cochlear injury induced by acoustic overexposure. Seventy-eight mice were exposed to a 4kHz pure tone at 128dB SPL for 4h. The auditory brainstem response (ABR) was used to examine the hearing thresholds. Cochlear morphology was examined to estimate the outer hair cell loss induced by acoustic overexposure. Methylprednisolone and quinacrine significantly alleviated the hearing threshold shift and hair cell loss induced by acoustic overexposure. RU486 antagonized the protective effect of methylprednisolone. The present findings suggest firstly that glucocorticoids exert protective effects against acoustic injury; secondly, that the protective effect of methylprednisolone was exerted by binding glucocorticoid receptors, and finally that activation of PLA2 may be involved in acoustic injury.

Acoustic Stimulation↗
PubMed2006

Synchronous unilateral parotid gland neoplasms of three different histological types.

A 67-year-old male with three synchronous tumors in the unilateral parotid gland is reported. Postoperative histological examinations confirmed the presence of three synchronous primary tumors, specifically pleomorphic adenoma, Warthin's tumor and salivary duct carcinoma, in the right parotid gland. To our knowledge, this is the first case report describing three different histological types in the unilateral parotid gland.

Adenolymphoma↗
PubMed2006

Successful treatment of eosinophilic otitis media using ramatroban: report of two cases.

OBJECTIVE: The pathogenesis of eosinophilic otitis media is not yet fully understood. The purpose of this paper is to describe the clinical course of our two patients with eosinophilic otitis media and to discuss the pathogenesis and treatment of this intractable condition. METHODS: Two cases of eosinophilic otitis media were treated with ramatroban. RESULTS: The middle ear effusion has been well controlled in both patients for more than 1 year with minimal corticosteroid therapy. CONCLUSIONS: Our experience suggests that the pathogenesis of eosinophilic otitis media is related to the pharmaceutical effects of ramatroban, i.e., inhibition of the thromboxane A2 receptor (TP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2).

Administration, Topical↗
PubMed2006

The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea.

Oxygen free radicals have been implicated in the pathogenesis of acoustic injury of the cochlea. The purpose of this study was to evaluate the effects of tempol (a superoxide anion scavenger), 3-aminobenzamide (a poly (ADP-ribose) synthetase (PARS) inhibitor), N-nitro-l-arginine (a non-selective nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (a selective neuronal NOS inhibitor) and aminoguanidine (a selective inducible NOS inhibitor) on acoustic injury. Mice were exposed to a 4 kHz pure tone of 110-128 dB SPL for 4h. Tempol, 3-aminobenzamide or N-nitro-l-arginine was intraperitoneally administered immediately before the onset of acoustic overexposure, while 7-nitroindazole or aminoguanidine was intraperitoneally administered every 12h starting immediately before the onset of acoustic overexposure. The threshold shift of the auditory brainstem response (ABR) and hair cell loss were then evaluated one and two weeks after acoustic overexposure. Tempol and 3-aminobenzamide significantly protected the cochlea against acoustic injury, whereas the NOS inhibitors did not exert any protective effect. These findings suggest that reactive oxygen species and PARS are involved in acoustic injury of the cochlea. However, further study is necessary to elucidate the roles of nitric oxide and nitric oxide synthase in acoustic injury.

Analysis of Variance↗
PubMed2006

Therapeutic time window of methylprednisolone in acoustic injury.

HYPOTHESIS: This study aims to investigate the therapeutic time window of methylprednisolone in acoustic injury. BACKGROUND: Although glucocorticoids have been widely used in the treatment of acoustic injury, the therapeutic time window of glucocorticoids in acoustic injury has never been examined. METHODS: Mice were exposed to 4-kHz pure tone of 128-dB sound pressure level for 4 hours. Auditory brainstem response was examined before, immediately after, and 2 weeks after acoustic overexposure. RESULTS: Methylprednisolone significantly improved the auditory brainstem response threshold shifts 2 weeks after acoustic overexposure when it was administered before or immediately after acoustic overexposure, but not when administered 3 hours after acoustic overexposure. CONCLUSION: The present findings suggest that methylprednisolone possesses protective effects against acoustic injury of the cochlea with a short therapeutic time window.

Analysis of Variance↗
PubMed2006

Protective effects of glucocorticoids on ischemia-reperfusion injury of outer hair cells.

OBJECTIVE: This animal study aimed to investigate effects of glucocorticoids on the functional recovery of outer hair cells (OHCs) after transient ischemia. METHODS: Distortion-product otoacoustic emission (DPOAE) was examined before, during, and after transient cochlear ischemia of 30 minutes using albino guinea pigs. RESULTS: DPOAE decreased to noise level during ischemia. On recirculation, DPOAE initially recovered with time until 20 minutes after the onset of reperfusion, but thereafter, the DPOAE level gradually decreased toward the noise level in the control animals. Prednisolone and methylprednisolone significantly improved the DPOAE level 60 minutes after the onset of reperfusion. CONCLUSIONS: The present findings suggest that glucocorticoids possess protective effects against ischemia-reperfusion injury of OHCs.

Animals↗
PubMed2005

Dehydroepiandrosterone sulfate reduces acoustic injury of the guinea-pig cochlea.

The present study was performed to determine effects of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid, on acoustic injury. Albino guinea pigs were exposed to a 2 kHz pure tone of 120 or 125 dB sound pressure level for 10 min immediately after intravenous administration of DHEAS. Statistically significant improvement in the compound action potential threshold shifts and in amplitude reduction of distortion-product otoacoustic emissions was observed 1 week after the acoustic overexposure in the animals treated with DHEAS. The present results suggest that DHEAS has a protective effect against acoustic injury of the cochlea.

Acoustic Stimulation↗
PubMed2005

Coexistence of pemphigus vulgaris and bullous pemphigoid in the upper aerodigestive tract.

Pemphigus vulgaris and bullous pemphigoid are autoimmune blistering diseases of the skin and the mucosa characterized by circulating autoantibodies. Coexistence of these lesions is extremely uncommon. We report herein a case of both pemphigus vulgaris and bullous pemphigoid which occurred in the upper aerodigestive tract. The diagnosis was made based on the circulating autoantibodies and direct immunofluorescent studies. The literature on this subject is reviewed.

Aged↗
PubMed2005

Protective effect of calcineurin inhibitors on acoustic injury of the cochlea.

This study examined the effect of immunosuppressants, cyclosporin A, FK506 and rapamycin on functional recovery of the cochlea after acoustic overexposure, in guinea pigs and mice. Thirty guinea pigs were exposed to a 2 kHz pure tone at 120 dB SPL for 10 min. The compound action potential threshold shift induced by acoustic overexposure was examined. Twenty-five mice were exposed to a 4 kHz pure tone at 128 dB SPL for 4h. Auditory brainstem response was used to examine the hearing threshold shift. In both the guinea pig and mouse experiments, cyclosporin A and FK506, intraperitonally given just before acoustic overexposure, significantly decreased the hearing threshold shift one or two weeks after acoustic overexposure. However, neither rapamycin nor the FK506 and rapamycin combined treatment groups showed improvement of the threshold shift. The present findings suggest that these two calcineurin inhibitors have a protective effect against acoustic injury of the cochlea, whereas the non-calcineurin inhibitor, rapamycin, not only has no effect against acoustic injury, but rather blocked the effect of FK506. This indicated a possible role of calcineurin against acoustic injury.

Action Potentials↗
PubMed2005

Primary osteogenic sarcoma of the ethmoid sinus: a case report.

Primary osteogenic sarcoma arising from the ethmoid sinus is an extremely rare condition. We report herein a 50-year-old female presenting with lacrimation. Computed tomography (CT) scan showed tumor calcification, which is a common feature of osteogenic sarcoma. Exploratory ethmoidectomy was performed, and histological examination confirmed the diagnosis of osteogenic sarcoma. Radiation therapy and chemotherapy failed to reduce the tumor size. The patient was finally treated by anterior craniofacial resection and orbital exenteration. Although primary osteogenic sarcoma of the ethmoid sinus is uncommon, the authors emphasize that osteogenic sarcoma should be suspected when tumor calcification was observed on CT scan and that adequate surgical resection with negative surgical margins remains the mainstay of treatment of this lesion.

Ethmoid Bone↗
PubMed2005

Hearing impairment in TRPV4 knockout mice.

Transient receptor potential channel vanilloid subfamily 4 (TRPV4), a member of TRP family, is a mechanosensitive non-selective cation channel. To investigate the role of TRPV4 in the cochlea, the hearing thresholds and effects of acoustic overexposure on the cochlea were examined in TRPV4 knockout mice. TRPV4 knockout mice at age 8 weeks exhibited normal, but those at 24 weeks revealed significantly higher thresholds by auditory brainstem response. The auditory threshold shift was significantly larger in the TRPV4 knockout than in the TRPV4+/+ mice 1 week after the acoustic overexposure of 128dB SPL. The present findings suggest that disruption of TRPV4 causes delayed-onset hearing loss and makes the cochlea vulnerable to acoustic injury.

Acoustic Stimulation↗
PubMed2005

Preoperative evaluation of ossicular chain abnormality in patients with conductive deafness without perforation of the tympanic membrane.

OBJECTIVE: To evaluate the usefulness of pure-tone audiometry, tympanometry, and liquid and acoustic reflex (AR) tests in the differential diagnosis of ossicular fixation and discontinuity. DESIGN: A prospective clinical trial. SETTING: Tertiary referral center. PATIENTS: Thirty-nine patients (46 ears) undergoing operations at University of Tsukuba Hospital, Tsukuba, Japan, from 1990 through 2003 for conductive deafness without perforation of the tympanic membrane. Clinical examinations for the preoperative diagnosis included pure-tone audiometry, tympanometry, and liquid and AR tests. We compared the preoperative diagnosis with the surgical findings. RESULTS: Although neither pure-tone audiometry nor tympanometry contributed to the differential diagnosis of ossicular chain abnormality, liquid and AR test results showed a significant difference between fixation and discontinuity of the ossicular chain. With the liquid test, bone conduction at lower frequencies was improved by filling the external auditory canal with water at lower frequencies in cases of ossicular fixation. In contrast to the findings observed in ossicular fixation, no improvement of the threshold of bone conduction was recognized at any frequency in the ears with ossicular discontinuity. In ipsilaterally stimulated AR, the reversed pattern was the most marked at 2000 and 500 Hz in ossicular fixation and discontinuity, respectively. CONCLUSION: Liquid and AR tests are reliable examinations for the differential diagnosis of ossicular fixation and discontinuity.

Acoustic Impedance Tests↗
PubMed2003

Glucocorticoids and dehydroepiandrosterone sulfate ameliorate ischemia-induced injury of the cochlea.

This study aimed to evaluate the effects of steroidal drugs on the functional recovery of the cochlea after transient ischemia. Albino guinea pigs were subjected to transient cochlear ischemia of 30 min duration, and the threshold shifts of the compound action potential (CAP) from the pre-ischemic values were evaluated 4 h after ischemia. Pre-ischemic administration of a glucocorticoid, prednisolone or methylprednisolone, significantly ameliorated the post-ischemic CAP threshold shifts as compared with control animals at a relatively wide range of doses. Post-ischemic administration of these glucocorticoids also exhibited protective effects. Pre-ischemic administration of dehydroepiandrosterone sulfate significantly decreased the post-ischemic CAP threshold shifts 4 h after ischemia. The present results indicate that glucocorticoids and dehydroepiandrosterone sulfate possess therapeutic effects against ischemic injury of the cochlea, such as idiopathic sudden sensorineural hearing loss.

Action Potentials↗
PubMed2003

Nevoid basal cell carcinoma syndrome: report of an aggressive case with ethmoid sinus invasion.

Nevoid basal cell carcinoma syndrome, also referred to as Gorlin-Goltz syndrome, is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar or plantar pits, ectopic calcification of the falx cerebri, and various skeletal developmental abnormalities. A minority of basal cell carcinomas demonstrate aggressive behavior and involve the craniofacial bones in nevoid basal cell carcinoma syndrome. A non-familial case of nevoid basal cell carcinoma syndrome with a basal cell carcinoma of the eyelid invading to the ethmoid sinus is reported.

Aged↗
PubMed2003

Involvement of poly(ADP-ribose) synthetase in acoustic trauma of the cochlea.

We investigated effects of poly(ADP-ribose) synthetase (PARS) inhibitors on acoustic trauma. Albino guinea pigs were intravenously given 3-aminobenzamide, nicotinamide or 3-aminobenzoic acid (an inactive analog of 3-aminobenzamide) just prior to exposure to a 2 kHz pure tone of 120 dB sound pressure level (SPL) for 10 minutes. The threshold of the compound action potential (CAP) and the amplitude of distortion-product otoacoustic emissions (DPOAEs) were measured before and 4 hours after the acoustic overexposure. Statistically significant decreases in the CAP threshold shifts and significant increases in the DPOAE amplitudes were observed 4 hours after the acoustic overexposure in the animals treated with 3-aminobenzamide or nicotinamide, whereas 3-aminobenzoic acid did not exert any protective effect. These results strongly suggest that excessive activation of PARS is involved in generation of the acoustic trauma.

Acoustic Stimulation↗