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Biomedical subjects

Takayuki Okano

Publications and source records attributed to Takayuki Okano.

7 recordsLinked to original sources

Cell-gene delivery of brain-derived neurotrophic factor to the mouse inner ear.

Sensorineural hearing loss is a common disability, but treatment options are currently limited to cochlear implants and hearing aids. Studies are therefore being conducted to provide alternative means of biological therapy, including gene therapy. Safe and effective methods of gene delivery to the cochlea need to be developed to facilitate the clinical application of these therapeutic treatments for hearing loss. In this study, we examined the potential of cell-gene therapy with nonviral vectors for delivery of therapeutic molecules into the cochlea. NIH3T3 cells were transfected with the brain-derived neurotrophic factor (Bdnf) gene using lipofection and then transplanted into the mouse inner ear. Immunohistochemistry and Western blotting demonstrated the survival of grafted cells in the cochlea for up to 4 weeks after transplantation. No significant hearing loss was induced by the transplantation procedure. A Bdnf-specific enzyme-linked immunosorbent assay revealed a significant increase in Bdnf production in the inner ear following transplantation of engineered cells. These findings indicate that cell-gene delivery with nonviral vectors may be applicable for the local, sustained delivery of therapeutic molecules into the cochlea.

Animals↗

Photonics: lasers producing tailored beams.

Compact lasers that can produce a range of beam patterns are important for progress in several areas, including the improvement of optical tweezers, ultra-high-density optical memory and microfluidics. Here we engineer photonic crystals to generate semiconductor lasers that produce a range of beam patterns while maintaining stable single-mode oscillation. Our results could contribute to the realization of compact lasers that are capable of producing diverse beam patterns on demand.

Journal Article↗

Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus.

This study aimed to evaluate the potential of embryonic stem cell-derived neural progenitors for use as transplants for the replacement of the auditory primary neurons, spiral ganglion neurons. Mouse embryonic stem cell-derived neural progenitors were implanted into the base of the cochlear modiolus of normal or deafened guinea pigs, which contains spiral ganglion neurons and cochlear nerve fibers. Histological analysis demonstrated the survival and neural differentiation of transplants in the cochlear modiolus and active neurite outgrowth of transplants toward host peripheral or central auditory systems. Functional assessments indicated the potential of transplanted embryonic stem cell-derived neural progenitors to elicit the functional recovery of damaged cochleae. These findings support the hypothesis that transplantation of embryonic stem cell-derived neural progenitors can contribute to the functional restoration of spiral ganglion neurons.

Animals↗

Elevation of superoxide dismutase increases acoustic trauma from noise exposure.

The generation of superoxide has been implicated as a cause of cochlear damage from excessive noise. Cu/Zn superoxide dismutase (SOD1) generally will protect against superoxide-mediated tissue injury but protection by this enzyme against noise trauma is controversial. This study assessed auditory function in C57BL/6 mice overexpressing SOD1 or treated with lecithinized SOD1 (PC-SOD1). Noise exposure caused significantly higher threshold shifts in PC-SOD1-treated animals than physiological saline-treated animals. Cochlear tissues of PC-SOD1-treated animals exhibited significant elevation of the levels in the SOD activity, not in the catalase activity, in comparison with those of saline-treated animals. Likewise, transgenic mice overexpressing SOD1 tended to suffer higher threshold shifts than nontransgenic littermates from noise exposure. The findings indicate that increasing SOD1 enhances auditory dysfunction following noise exposure.

Acoustic Stimulation↗

A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: review of Japanese cases and evaluation of risk for internal malignancy.

A 68-year-old Japanese male with a five-year-history of lung carcinoma showed recurrent blisters and erosions on the oral and genital mucosae and the skin. The patient complained of dyspnea due to severe laryngeal stenosis and underwent a tracheostomy. A skin biopsy specimen showed a subepidermal blister and linear deposits of IgG and C3 at the basement membrane zone of the epidermis. Indirect immunofluorescence examination demonstrated circulating IgG anti-basement membrane zone autoantibodies that reacted to epiligrin on immunoblotting. Based on a diagnosis of anti-epiligrin cicatricial pemphigoid, he was treated with prednisolone, minocycline hydrochloride and nicotinamide. Although no new skin lesions appeared, he died of lung carcinoma five months after the tracheostomy. A review of reported cases with anti-epiligrin cicatricial pemphigoid in Japan disclosed that 5 of 16 cases (31.2%) were complicated by internal malignancies.

Aged↗

[Clinical study of congenital cholesteatoma of the middle ear].

We studied 35 ears of 34 patients with congenital cholesteatoma who were operated between June 1992 and May 2003, focusing on the localization and progression of congenital cholesteatoma. Patients were 2 to 55 years of age. Congenital cholesteatoma was diagnosed based on two intraoperative findings: 1) no continuity between the tympanic membrane and cholesteatoma, 2) no presence of perforation, retraction, or granulation of the tympanic membrane. All patients had closed-type cholesteatoma, and none formed open-type cholesteatoma, which grows as a flat sheet of epidermis. The primary site of congenital cholesteatoma was classified into 3 types; 1) anterior-superior quadrant, 2) posterior-superior quadrant, and 3) epitympanic, and the origin of these three types of congenital cholesteatoma was difficult to explain by a single theory. We operated on 31 ears by canal wall up tympanoplasty and on 4 ears by canal wall down tympanoplasty. On all but 4 ears, we performed planned-staged operation, including second-look operations, in case of recurrence or residual cholesteatoma. Improvement in hearing after surgery was seen in 22 of the 26 ears treated and followed up for more than 6 months after surgery. By drawing all localization of congenital cholesteatoma in 35 ears, we studied the progression of congenital cholesteatoma and speculated on the original primary site. Congenital cholesteatoma in restricted areas consequently implies good results in hearing after surgery, making earlier diagnosis and treatment desirable.

Adolescent↗

[Congenital auditory ossicle malformation without external ear abnormality].

In 29 ears of 24 patients with auditory ossicle malformation, but without external ear abnormalities, who were operated on at our clinic in the 10 years between June 1993 and June 2002, we studied the condition of ossicles, preoperative examination, surgical procedures, and postoperative hearing improvement. Our study did not include patients with cholesteatoma or those with only fixed stapes but without ossicular deformity. Samples were 12 ears of 11 men and 17 ears of 13 women. We clinically distinguished 3 major categories: (i) discontinuity between the incus and stapes with mobile stapes, (ii) congenital fixation of the stapes with ossicular deformity, and (iii) congenital fixation of the malleus and deformity of the incus with mobile stapes. We classified each category into minor abnormalities based on the condition of the long process of the incus, the superstructure of the stapes, and the stapes footplate. We conducted auditory ossicle reconstruction by mobilization of the malleus and incus in 2 ears, by type III tympanoplasty in 5 ears, by type IV tympanoplasty in 13 ears, and by stapes surgery in 8 ears. Improvement in hearing after the operation was observed in 25 of the 29 ears treated. In the classification of the auditory ossicle malformation without external ear abnormalities, we should evaluate discontinuity or fixation of the ossicles and their deformity. This requires that varied ossicular reconstruction be prepared for surgery, but the possibility of hearing improvement is high, so intensive treatment is needed in many cases of auditory ossicle malformation.

Adolescent↗