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Biomedical subjects

Ken Ito

Publications and source records attributed to Ken Ito.

35 records · Page 2Linked to original sources

Overexpression of the Wilms' tumor gene W T1 in primary astrocytic tumors.

Expression of the Wilms' tumor gene W T1 in primary astrocytic tumors was examined using a quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) or immunohistochemistry. Real-time RT-PCR showed that W T1 mRNA was expressed at various levels in all of the 25 astrocytic tumors examined. Immunohistochemical analysis showed that W T1 protein was expressed in 5 of 6 low-grade astrocytic tumors (grade I-II) and all of 18 high-grade ones (grade III-IV), and that expression levels of W T1 protein in high-grade tumors were significantly higher than those in low-grade ones. W T1 protein was not detected in the normal glial cells contained in the tumor specimens. Furthermore, treatment with W T1 antisense oligomers specifically inhibited growth of glioblastoma cell lines, U87-MG, A172, and T-98G. These results may indicate that the W T1 gene plays an important role in tumorigenesis of primary astrocytic tumors.

Adolescent↗

Assessment of total middle ear reconstruction by patient survey correlated with clinical findings.

OBJECTIVE: Our objective was to assess, by patient survey and clinical examination, the results of correctional total middle ear reconstruction of problematic mastoid cavities following radical or modified radical mastoidectomy. SETTING: This study was performed in an academic tertiary referral center. PATIENTS: The study consisted of a retrospective survey, using the modified hearing satisfaction scale, of 50 patients, who had undergone total middle ear reconstruction of their problematic mastoid cavities. The survey results were correlated with their postoperative clinical findings. RESULTS: Postoperatively, 98% of these patients expressed satisfaction in terms of improvement of their preexisting otorrhea (median of 4.32 satisfied), 65% were satisfied with their hearing and 85% were satisfied with the overall of this operation. The survey results had a good correlation with the audiometric findings and the clinical findings, i.e. the surgery resulted in a dry ear in all 50 patients and 51% of these patients showed hearing improvement of more than 5 dBHL. CONCLUSIONS: This study indicates that most patients were satisfied with the outcomes of this operation. The patients' point of view and the postoperative clinical data both indicate that total middle ear reconstruction is an excellent procedure for correcting problematic mastoid cavities following a radical or modified radical mastoidectomy. The hearing satisfaction scale is a useful instrument for assessing patient satisfaction following this surgical procedure.

Activities of Daily Living↗

Use of cartilage plate as tympanic membrane in total middle ear reconstructive surgery for infected radicalized ear.

OBJECTIVE: To evaluate the usefulness of cartilage plates as tympanic membranes combined with total middle ear reconstructive surgery for radicalized ears. STUDY DESIGN: Retrospective study between 1994 and 1999. SETTING: Tertiary care referral medical center. PATIENTS: Seven patients had seven ears with severe chronic otorrhea after radical mastoidectomy. All patients had severe to profound sensorineural hearing loss and expected a trouble-free ear rather than improved hearing after surgery. Patients were followed up for 4 years postoperatively. METHODS: After the middle ear space was cleaned, the tympanic membrane was reconstructed using a plate prepared from the tragal cartilage. The major part of the posterior wall was reconstructed using a conchal cartilage plate. Cortical bone segments were inserted to support the cartilage plate. RESULTS: Preoperatively, cultures of ear discharge were positive for various bacteria. Recovery with dry eardrums was noted in six patients, and one patient showed minimal erosion. No postoperative complications were encountered, but the hearing threshold did not improve postoperatively. CONCLUSIONS: Total middle ear reconstructive surgery is suitable for patients with chronic otorrhea complicating radical mastoidectomy. The use of cartilage plates seems to be clinically appropriate, particularly for patients with severe infection who expect a trouble-free ear rather than hearing gain after surgery.

Adult↗

Retinal neuronal death induced by intraocular administration of a nitric oxide donor and its rescue by neurotrophic factors in rats.

PURPOSE: To investigate the neurotoxic outcome in the rat retina exposed to nitric oxide (NO) released from an NO donor and to evaluate the effects of neurotrophic factors on the survival of NO-damaged retinal cells. METHODS: An NO releasing compound, N-ethyl-2-(1-ethyl-2-hydroxy-2-nitrosohydrazino) ethanamine (NOC 12), was intravitreously injected into a rat's right eye. The influences of NOC 12 on retinal neurons and the neuroprotective effects of ciliary neurotrophic factor (CNTF) or brain-derived neurotrophic factor (BDNF) on NOC 12-mediated damage were estimated by counting cells in the ganglion cell layer (GCL) and by measuring the thickness of retinal layers. The exact count of retinal ganglion cells (RGCs) was also confirmed by means of retrograde labeling with a fluorescent tracer. RESULTS: Morphometric analyses of retinal damage in the NOC 12-exposed eyes demonstrated a significant and dose-dependent decrease in cell density in the GCL and a reduction in thickness of the inner plexiform layer and inner nuclear layer, but not of the outer nuclear layer. TdT-dUTP terminal nick-end labeling of retinal sections after intravitreous injection of NOC 12 demonstrated that NO could trigger apoptotic cell death. The counting of the RGCs labeled with a fluorescent tracer suggested that a decrease in GCL cell density induced by NOC 12 reflects a loss in RGCs. Treatment with CNTF (1 microg) or BDNF (1 microg) before the intravitreous injection of NOC 12 (400 nmol) demonstrated that these trophic factors have protective effects against NO-induced neuronal cell death in the retina. CONCLUSIONS: Exogenous NO induces retinal neurotoxicity, suggesting that NO plays a pathogenic role in degenerative retinal diseases. BDNF and CNTF protect retinal neurons from NO-mediated neurotoxicity.

Animals↗

Retinal neurotoxicity of nitric oxide donors with different half-life of nitric oxide release: involvement of N-methyl-D-aspartate receptor.

We compared the degree of neurotoxic outcome in the retina exposed to three nitric oxide (NO) donors with different half-life of NO release. Intravitreal injection of NO donors resulted in a significant decrease in cell density in the ganglion cell layer and thinning of the inner plexiform layer in a half-life time-dependent manner. Concurrent injection of an NO-trapping reagent with an NO donor abolished NO donor-induced retinal damage. (+)-MK-801 also prevented NO-induced retinal damage, indicating that N-methyl-D-aspartate receptors are partly involved in NO-induced neurodegeneration. These results may be relevant to a pathogenic role of NO - glutamate receptor in several ophthalmic disorders.

Animals↗

Postlingual collapse of language and its recovery after cochlear implantation.

A 6-year-old boy lost his normally-developed language ability within 2 months after bilateral sudden peripheral deafness. The boy became non-communicative with others, restless with frequent meaningless bursts of shouts (communication skills equivalent to 9-11 months of language development: a rapid breakdown of language). Since conservative methods were ineffective, cochlear implantation was performed. A surprising success was observed: he regained the language retracing the normal developmental stages and caught up with his contemporaries in 2 years. Behavioral improvement paralleled his language development. This case (1) provides insights into the brain function with respect to language acquisition, in relation to the plasticity during the 'critical period' of language learning, (2) reveals the close relationship between language development and behavior, and (3) suggests the predominance of auditory stimulation in learning language.

Child↗

Substance P mobilizes intracellular calcium and activates a nonselective cation conductance in rat spiral ganglion neurons.

We demonstrate the expression of functional tachykinin receptors in rat spiral ganglion neurons (SGNs) using calcium signal measurement and whole-cell patch clamp recording. Substance P (SP; 10 microm, 1 s application) induced a transient increase in intracellular calcium. The SP dose-response study showed an EC50 of 18.8 microm and a Hill slope of 0.77. Comparison between specific agonists for the three tachykinin receptor (NKR) types showed the potency NKR3 > NKR1 > NKR2 at 10 microm. The Ca2+ response could be evoked in Ca2+-free medium and was blocked by N-ethylmaleimide and U-73122, indicating that Ca2+ was released from intracellular stores via a G-protein and phospholipase C pathway. Under whole-cell voltage clamp recording at a holding potential of -50 mV, SP (10 microm, 1 s) evoked a slowly developing transient inward current. The current reversed near to 0 mV and ionic permeability experiments revealed a cation nonselective conductance also permeable to large organic cations such as N-methyl-D-glucamine and tetraethylammonium. Neither removing extracellular calcium nor chelating intracellular calcium with 10 mm BAPTA could block the SP-evoked current. This conductance appeared coupled to G-protein activation as intracellular GDP-betaS blocked the SP-evoked current. Mutual desensitization and occlusion studies with acetylcholine and ATP showed that the SP-evoked conductance share effector channels and/or intracellular processes with the purinergic/cholinergic conductance. In SGNs, SP could have both a trophic action, via a calcium response, and a neuromodulatory role, by a depolarizing action through the activation of nonselective cation channels.

Acetylcholine↗

Stomal recurrence after total laryngectomy for squamous cell carcinoma of the larynx.

OBJECTIVE: Stomal recurrence after total laryngectomy is one of the most serious issues in the management of laryngeal carcinoma. The management of stomal recurrence, including chemotherapy, radiotherapy, and surgery, has been reported as unsatisfactory. STUDY DESIGN AND SETTING: From 1985 to 1995, 69 patients underwent total laryngectomy for the treatment of laryngeal cancer at the University of Tokyo Hospital. To identify the risk factors for stomal recurrence, we analyzed these patients according to various clinicopathological factors. RESULTS: Stomal recurrence developed in 6 of 69 patients who underwent total laryngectomy for laryngeal carcinoma. Statistical analysis reveals that primary site, preoperative tracheotomy, and paratracheal lymph node metastasis are significant risk factors for stomal recurrence. CONCLUSION: Intensive follow-up should be performed for patients with glottic carcinoma who had preoperative tracheotomy, paratracheal lymph node metastasis, or both to detect stomal recurrence at an early stage.

Adult↗

Total middle ear reconstructive surgery for the radicalized ear.

OBJECTIVE: To evaluate the efficacy of total middle ear reconstructive surgery (TMRS) for patients with open cavity problems. STUDY DESIGN: Retrospective study of patients treated between 1994 and 1997. SETTING: Tertiary care, referral medical center. PATIENTS: Fifty-nine consecutive patients (62 ears) with open cavity problems (draining ears) who underwent TMRS. MAIN OUTCOME MEASURES: Postoperative states of the ears and complications were evaluated in two groups, with and without persistent purulent otorrhea at the time of surgery. RESULTS: In the noninfected group, ears without otorrhea were maintained in 12 (100%) of 12 ears in the short term and 10 (83%) of 12 ears in the long term. In the infected group, the proportions were 40 (80%) of 50 ears and 35 (73%) of 48 ears, for the short and long terms, respectively. Hollowing and/or retraction of the reconstructed canal wall was observed in 1 (8%) of 12 ears of the noninfected group and in 15 (31%) of 48 ears of the infected group after long-term follow-up. Postoperative complications were encountered in 9 ears (14.5%) in the infected group only. CONCLUSIONS: Total middle ear reconstructive surgery is considered useful for the management of persistent discharge from radicalized cavities. It was found important to minimize infection at the time of surgery to achieve satisfactory results.

Adult↗

Facial canal anatomy in patients with microtia: evaluation of the temporal bones with thin-section CT.

PURPOSE: To ascertain the location of the facial nerve in patients with microtia by using thin-section computed tomography (CT). MATERIALS AND METHODS: Thin-section CT was performed in 66 ears of patients with microtia (unilateral, n = 12; bilateral, n = 34) and mandibulofacial dysostosis (MFD, n = 20). Findings were compared with those in 22 ears with normal auricles (control group) by using the Dunnett two-sided t test. RESULTS: The facial nerve at the mastoid portion in patients with MFD was 2 mm more lateral and 3 mm more anterior than that in control subjects (P <.01). The same portion in patients with microtia was 3 mm more anterior than that in the control subjects (P <.01). The distance between the facial nerve and the most lateral point of the temporal bone in patients with MFD was 10 mm shorter and that in patients with bilateral microtia was 3 mm shorter than that in the control subjects (P <.01). CONCLUSION: The facial nerve in patients with microtia was not more lateral from the Bill bar (vertical crest) than that in control subjects. The facial nerve in patients with MFD was different from that in patients with microtia who had no other head anomalies.

Case-Control Studies↗

Nonselective cation conductance activated by muscarinic and purinergic receptors in rat spiral ganglion neurons.

The present study characterizes the ionic conductances activated by acetylcholine (ACh) and ATP, two candidate neuromodulators, in isolated spiral ganglion neurons (SGNs). Brief application (1 s) of ACh evoked in a dose-dependent manner (EC(50) = 4.1 microM) a reversible inward current with a long latency (average 1.3 s), at holding potential (V(h)) = -50 mV. This current was reversibly blocked by atropine and mimicked by muscarine. Application of ATP also evoked a reversible inward current at V(h) = -50 mV, but the current showed two components. A fast component with a short latency was largely reduced when N-methyl-D-glucamine (NMDG) replaced extracellular sodium, implying a P2X-like ionotropic conductance. The second component had a longer latency (average 1.1 s) and was presumably activated by metabotropic P2Y-like receptors. The second component of ATP-evoked current shared similar characteristics with the responses evoked by ACh: the current reversed near 0 mV, displayed inward rectification, could be carried by NMDG, and was insensitive to extracellular and intracellular calcium. This ACh-/ATP-evoked conductance was reversibly inhibited by preapplication of ionomycin. These results suggest that muscarinic receptors and purinergic metabotropic receptors activate a similar large nonselective cation conductance via a common intracellular pathway in SGNs, a candidate mechanism to regulate neuronal excitability of SGNs.

Acetylcholine↗

Vocal cord paralysis after surgery for thoracic aortic aneurysm.

OBJECTIVE: To determine the incidence, etiology, prognosis, and treatment of vocal cord paralysis (VCP) after surgery for thoracic aortic aneurysm (TAA). STUDY DESIGN: Retrospective study performed between 1989 and 1995. SETTING: Academic, tertiary care, referral medical center. PATIENTS: Seventy-one TAA patients underwent surgery at the Kameda Medical Center between 1989 and 1995. RESULTS: Sixty-two of 71 patients were examined postoperatively for voice quality. Twenty patients (32%) had hoarseness develop caused by VCP, as confirmed by laryngoscopy. The left recurrent laryngeal nerve had been sacrificed in 1 patient during surgery, but it was preserved in the remaining 19 patients. Unilateral left VCP was noted in 19 patients, and bilateral VCP occurred in 1 patient. The incidence of VCP was higher in those patients who underwent surgery for type I aneurysms (9 of 14 patients, 64%). In 16 of the 19 patients (84%) who received follow-up for > 6 months, vocal cord movement did not return to normal. Surgery to improve voice quality, arytenoid adduction in five patients and intracordal injection in two patients, was performed with success. CONCLUSIONS: Our results indicate that surgery for TAA is associated with a relatively high incidence of VCP. VCP occurred despite preservation of the recurrent laryngeal nerve, and the paralysis did not show a spontaneous recovery even 6 months after surgery.

Adult↗

Overexpression of the Wilms' tumor gene WT1 in esophageal cancer.

BACKGROUND: The Wilms' tumor gene WT1 is overexpressed in various kinds of solid cancers. However, it remains unclear whether WT1 is expressed in esophageal squamous cell carcinoma. MATERIALS AND METHODS: Expression of the WT1 gene was examined by real-time RT-PCR in 12 esophageal squamous cell carcinoma (ESCC) and by immunohistochemistry in 9 of these 12 and another 29. RESULTS: Real-time RT-PCR showed that the WT1 mRNA was overexpressed in all of the 12 ESCC examined Immunohistochemical analysis showed that the WT1 protein was overexpressed in ESCC cells in 36 (95%) of the 38 examined Furthermore, expression of the WT1 protein was examined in 20 esophageal squamous dysplasia. The WT1 protein was overexpressed in 5 (45%) out of 11 mild dysplasia and in 8 (89%) out of 9 moderate to severe dysplasia. CONCLUSION: These results may indicate an important role of the WT1 gene in the tumorigenesis of ESCC.

Adult↗