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T Tono

Publications and source records attributed to T Tono.

At least 37 records · Page 2Linked to original sources

Increase in glutamate-aspartate transporter (GLAST) mRNA during kanamycin-induced cochlear insult in rats.

Kanamycin (KM)-induced changes in expression of the gene for glutamate-aspartate transporter (GLAST) in the rat cochlea were analyzed by Northern blotting. With the administration of KM (600 mg/kg/day) once daily for 20 days, the expression of GLAST mRNA gradually increased and reached a peak on day 20. Although the expression of GLAST mRNA remained at a high level until 12 days after the completion of the KM treatment, it then fell to the normal level within 2 months. Such KM treatment resulted in loss of both inner and outer hair cells and a concomitant profound permanent threshold shift. The present findings suggest that during KM administration, high concentrations of extracellular glutamate released by collapsing hair cells induced GLAST mRNA expression. Increased GLAST mRNA might play an important role in the prevention of the secondary death of spiral ganglion neurons from glutamate neurotoxicity.

ATP-Binding Cassette Transporters↗

Power Doppler sonography of hepatocellular carcinoma treated by transcatheter arterial chemoembolization. Assessment of the therapeutic effect.

PURPOSE: To evaluate the usefulness of power Doppler sonography (PDS) in assessing the therapeutic effect of transcatheter arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC). MATERIAL AND METHODS: TACE was performed in 43 patients (48 lesions) with HCC. All patients were examined with both PDS and color Doppler sonography (CDS) to assess the therapeutic results 1 week after TACE. Follow-up hepatic angiography was performed in 39 patients 3-4 months after TACE and then CT after iodized oil reinjection was also performed 3-4 weeks after a repeat TACE; in the remaining 4 patients, hepatectomy was performed within one month after chemoembolization and histologic study was undertaken to confirm the Doppler findings. RESULTS: Determination of therapeutic results with PDS and CDS were in agreement with those of follow-up findings in 37 and 29 of the 48 lesions, respectively. There was a significant difference in overall accuracy (p=0.038) between PDS and CDS results. CONCLUSION: PDS is more effective than CDS for evaluating changes in tumor vascularity after TACE. PDS may also replace angiography in assessing the therapeutic effects of TACE for HCCs, except in deep-seated areas.

Aged↗

[Clinical experiences and postoperative results with partially implantable middle ear implant].

A partially implantable middle ear implant using an ossicular vibrator of a piezoelectric ceramic bimorph has recently been developed in Japan as a new rehabilitative method for hearing. Four patients at the Miyazaki Medical College Hospital were implanted with this device between September 1994 and October 1996. Implantation of the internal component was performed under local anesthesia after confirmation of sufficient sensitivity to the ossicular vibrator in an intraoperative vibratory hearing test. All patients regained socially useful hearing with the middle ear implant without any foreign body reactions or recurrence of otitis media. None of the cases showed any elevations of bone conduction thresholds 2 to 4 years postoperatively. Natural and clear sounds without interference noise and howling due to acoustic feedback were highly satisfactory in all patients. However, the first case, who had an implant in an ear following cholesteatoma surgery using the intact canal wall technique, experienced about a 10dB deterioration of the average hearing level with the implant 2 years after implantation. Gradual deterioration appeared to be caused by the retracted tympanic membrane interfering with the mobility of the ossicular vibrator. The following three cases were implanted in ears previously operated on by radical mastoidectomy, showing stable or improving hearing results with the implant. Closure of the external canal skin at the cartilaginous portion at the time of implantation seemed appropriate to maintain a sufficient middle ear space for the ossicular vibrator to work properly. Our case study confirms that the partially implantable middle ear implant is a safe and useful tool for patients with mixed deafness which cannot be satisfactorily rehabilitated by tympanoplasty and/or a conventional hearing aid.

Deafness↗

[The efficacy and limitation of hepatic arterial infusion chemotherapy for colorectal liver metastases].

We investigated the efficacy and limitation of hepatic arterial infusion (HAI) chemotherapy for colorectal liver metastases. In terms of prophylactic HAI following curative resection of liver, the 5-year disease-free survival of HAI group (12 g of 5-FU administered in 6 weeks) was 66.7%, whereas that of randomly selected control group was 20.0%. The difference was statistically significant (p = 0.045). Recurrent disease was confirmed in three cases of HAI group (one in liver) and in 8 patients of the control group (6 in liver). However, the overall survival was not significantly different between the groups. Thus, the short-term HAI of 5-FU is effective in decreasing the recurrence of disease. As for the treatment of unresectable liver metastases, some patients received HAI of 5-FU (1,000-1,500 mg/w) showed prolonged survival with partial remission of the disease. However, the 1-, 2-, and 3-year cumulative survival of HAI group (n = 27) was 69.3, 34.1 and 11.4%, respectively, against 61.3, 22.6 and 9.4%, respectively, in the transarterial embolization (TAE) group (n = 31). Therefore it is important to estimate the effect in the early phase of HAI, and aggressively continue the treatment in selected patients for whom it is suitable.

Administration, Oral↗

Tolerance induction by anti-CD2 plus anti-CD3 monoclonal antibodies: evidence for an IL-4 requirement.

Anti-CD2 mAb plus anti-CD3 mAb induce alloantigen specific tolerance. We sought to determine whether Th2 cytokines are involved in the induction of tolerance in this model. Addition of anti-IL-4 mAb or anti-IL-10 mAb to anti-CD2 plus anti-CD3 treatment abrogated tolerance and resulted in graft survivals of 26+/-4 and 25+/-5 days, respectively. Splenocytes from the anti-IL-4 mAb and anti-IL-10 groups had greater proliferation in response to alloantigen than either tolerant or naive groups. Cytokine analysis of MLR supernatants showed increased IL-10 in the tolerant group and increased IFN-gamma in the anti-IL-4 mAb treated group. Donor-specific alloantibody responses in untreated immune animals had a predominantly Th1 (IgG2a) alloantibody response, while the tolerogenic regimen reduced the ratio of IgG2a:IgG1 titers. The addition of anti-IL-4 mAb to the tolerogenic regimen partly restored the Th1-related IgG2a response. Tolerance did not develop in IL-4 knockout animals treated with anti-CD2 plus anti-CD3 (mean graft survival, 27+/-5 days). Restoration of IL-4 to IL-4 knockout animals by gene transfer with plasmid DNA resulted in prolongation of survival to 46+/-7 days, while adoptive transfer of wild-type splenocytes into IL-4 knockout recipients resulted in indefinite graft survival (>60 days) and indefinite survival of second donor-type grafts. IL-10 gene transfer to IL-4 knockout recipients did not prolong graft survival (28+/-4). These results demonstrate that tolerance in this model is mediated at least in part by Th2-type cells that secrete IL-4, promote IL-10 and IgG1 production, and inhibit alloantigen reactivity.

Animals↗

High potassium-induced glutamate release in the cochlea: in vivo microdialysis study combined with on-line enzyme fluorometric detection of glutamate.

The time course of changes in perilymphatic glutamate release and their Ca2+-dependency were studied in the guinea pig cochlea during high K+-evoked depolarization. The glutamate concentration was analyzed continuously by an enzyme-linked fluorometric assay combined with microdialysis. Two peaks of glutamate increase were found in response to perfusion for 10 min. In the absence of Ca2+, the first peak was diminished, whereas the inhibition of the second peak was minimal.

Animals↗

Changes of perilymphatic glutamate and cochlear blood flow following ischemia.

Dynamic changes of perilymphatic glutamate and cochlear blood flow were measured simultaneously in the guinea pig following cochlear ischemia. Glutamate was measured by the microdialysis technique with a probe inserted into the scala tympani at the basal turn. Cochlear blood flow was monitored with a laser-Doppler probe on the lateral wall of the second cochlear turn. Both parameters were measured before and after electrocauterization of the anterior inferior cerebellar artery and other vessels supplying the internal auditory canal. In four animals, glutamate increased with a decline of cochlear blood flow and then decreased with recovery of blood flow. No normalization of glutamate was observed in seven animals with a persistent decrease of blood flow. The results of this study indicate that the glutamate regulating system in the cochlea is dependent on cochlear blood flow.

Animals↗

Effects of trimetaphan-induced deliberate hypotension on human cochlear blood flow.

In order to observe the reaction of cochlear blood flow (CBF) to trimetaphan (TMP)-induced hypotension, CBF was measured with laser-Doppler flowmetry in 7 human subjects during general anaesthesia for middle ear surgery. All subjects showed a decrease in mean arterial pressure (MAP) during intravenous infusion of TMP, followed by a gradual return to the baseline level after termination of the infusion. The CBF generally followed the MAP changes with the same pattern. Three of the seven subjects demonstrated a CBF change larger than the maximum MAP change, indicating the lack of a local autoregulatory mechanism in CBF. On the other hand, CBF changes were smaller in magnitude than the maximum change in MAP for the rest of the subjects, suggesting an autoregulatory mechanism in CBF. However, since the audiograms from these subjects indicated profound damage along the cochlear basal turn probably due to middle ear inflammation, concomitant vascular damage in this region offers another possible explanation for the inappropriate CBF changes. The present observations may also suggest that deliberately TMP-induced hypotension has a potentially harmful effect on CBF during otological surgery that attempts to preserve or improve hearing.

Adult↗

Quantitative immunogold cytochemistry reveals sources of glutamate release in inner ear ischemia.

Glutamate is thought to be a major neurotransmitter between hair cells and afferent dendrites in the inner ear. However, excessive glutamate is known to be excitotoxic, and may be involved in ischemic neuronal damage in the central nervous system. The glutamate concentration in the perilymph has been reported to increase during ischemia, but the source of glutamate is still unclear. In the present study, we have used post-embedding immunogold cytochemistry to analyse changes in the cellular distribution of glutamate in the guinea pig organ of Corti during ischemia. The areal gold particle densities in the inner hair cells of the ischemic side were lower than those of the control side, indicating that glutamate may be released from the hair cells during ischemia. Adjacent supporting cells (border cells) also showed a decrease in particle density, suggesting that they constitute an additional source of glutamate.

Animals↗

[Intra-arterial chemotherapy to improve quality of life in cases of unresectable advanced or recurrent breast cancer].

We performed repetitive intra-arterial infusion chemotherapy (I.A.) with epirubicin in order to improve the quality of life (QOL) in 3 cases with locally advanced or recurrent breast cancer which were diagnosed as surgically unresectable and seemed uncontrollable by outpatient systemic chemotherapy. The patients were admitted to our hospital for chest wall invasion, lymph node metastasis, bleeding, pain, or edema in upper extremity. Therapeutic effects included 1 case of CR and 2 cases of PR in the primary site, and similar effects were obtained in metastasized lymph nodes. We could perform mastectomy in both of the 2 cases with locally advanced cancer after I.A., Although leukocytopenia, which was the dose limiting factor in this regimen, was observed in all 3 cases, it was Grade 2 or 3 and recovered by G-CSF. With regard to their QOL, symptoms which had driven them to inpatient treatment remarkably improved in all of the cases. Thus, after 2 series of I.A. they could receive maintenance systemic chemotherapy as outpatients. Our findings showed that the I.A. as a local control treatment in patients with unresectable advanced or recurrent breast cancer is useful for the improvement of their QOL.

Antibiotics, Antineoplastic↗

[Long-term survival in a case of multiple liver metastasis from postoperative gastric cancer effectively treated by hepatic intraarterial infusion chemotherapy using MMC and pirarubicin].

We experienced a case of multiple liver metastasis from postoperative gastric cancer who showed long-term survival with hepatic arterial infusion chemotherapy (HAI) of MMC and pirarubicin. A catheter was inserted into the hepatic artery, and 4 mg of MMC and 20 mg of pirarubicin were administered through an implantable port catheter every two to four weeks. The total dose of MMC and pirarubicin by the time of this report was 164 mg and 820 mg, respectively. The follow-up CT scan 2 months after the beginning of HAI showed a decrement of the liver tumors. The decrease rate at 12 and 17 months was 50% and 70%, respectively, which was diagnosed as partial response (PR). The therapeutic effect at 49 months is still PR without any sign of tumor enlargement of extra hepatic lesion.

Antineoplastic Combined Chemotherapy Protocols↗

Cochlear implantation in a patient with profound hearing loss with the A1555G mitochondrial mutation.

OBJECTIVE: This study aimed to describe the performance of a cochlear implant in a patient with profound hearing loss with the A1555G mitochondrial mutation. SETTING: The study was conducted at two university hospitals. PATIENT: A 50-year-old Japanese man in whom bilateral profound hearing loss developed after administration of streptomycin at the age of 23 participated. The pedigree of the family showed exclusively maternal transmission of hearing impairment. INTERVENTION: Genetic study and auditory rehabilitation with a cochlear implant were performed. RESULTS: The A1555G point mutation was identified from the patient's mitochondrial DNA. Since activation of the implant, the patient has been using it successfully with a monosyllable recognition score of 78% using Japanese word lists for speech audiometry. CONCLUSIONS: The current case indicated that cochlear implantation may be a valuable choice of therapy for the patient with profound hearing loss with the A1555G mutation. The excellent auditory performance with a cochlear implant suggests that hearing loss associated with this mutation is primarily caused by insult to the cochlear tissue containing rich mitochondria (i.e., hair cells or stria vascularis or both), not to the cochlear nerve and its central connections.

Antibiotics, Antitubercular↗

[High-resolution CT of otosclerosis].

High-resolution CT (HRCT) scans of thirty-two patients (60 ears) with the clinical diagnosis of fenestral otosclerosis were evaluated retrospectively. HRCT was performed with 1-mm-thick targeted sections and 1-mm (36 ears) or 0.5-mm (10 ears) intervals in the semiaxial projection. Seven patients (14 ears) underwent helical scanning with a 1-mm slice thickness and 1-mm/sec table speed. Forty-five ears (75%) were found to have one or more otospongiotic or otosclerotic foci on HRCT. In most instances (30 ears), the otospongiotic foci were found in the region of the fissula ante fenestram. No significant correlations between CT findings and air conduction threshold were observed. We found a significant relationship between lesions of the labrinthine capsule and sensorineural hearing loss. We conclude that HRCT is a valuable modality for diagnosing otosclerosis, especially when otospongiotic focus is detected.

Adolescent↗

Blockade of multiple costimulatory receptors induces hyporesponsiveness: inhibition of CD2 plus CD28 pathways.

T-lymphocyte activation requires engagement of the T cell receptor with antigen-major histocompatibility complex, and simultaneous ligation of costimulatory pathways via the lymphocyte receptors CD2 and CD28/ CTLA4. Anti-CD2 monoclonal antibody (mAb) blocks the interaction of the antigen-presenting cell receptor CD48 with its ligand CD2, whereas CTLA4Ig binds with high affinity to the antigen-presenting cell ligands B7-1 and B7-2, blocking their interaction with CD28/CTLA4. We tested the immunosuppressive effects of simultaneously blocking both costimulatory pathways. Using donor C57BL/6J (H2b) hearts transplanted to CBA/J (H2k) recipients, anti-CD2 mAb plus CTLA4Ig administered at the time of transplantation prolonged cardiac allograft mean survival time to >120 days compared with untreated controls (12.2+/-0.5 days, P<0.01), anti-CD2 mAb alone (24.8+/-1.0 days, P<0.01), or CTLA4Ig alone (55.0+/-2.0 days, P<0.01). Retransplantation of these recipients with donor-specific and third-party grafts demonstrated that hyporesponsiveness and tolerance were achieved. In vitro stimulation of lymphocytes from tolerant recipients with donor-specific alloantigen resulted in normal cytotoxic T lymphocyte and mixed lymphocyte reaction responses, showing that clonal deletion or anergy did not occur, but that graft adaptation or suppression likely helped to maintain long-term graft survival. In vitro combinations of anti-CD2 mAb and CTLA4Ig suppressed the generation of allogeneic cytotoxic T lymphocytes (58%) and the mixed lymphocyte reaction (36%); CTLA4Ig was more effective in this regard and the two agents were not synergistic. Anti-CD2 mAb and CTLA4Ig suppressed mitogen-driven proliferation in differential fashions, suggesting that they affected independent signaling pathways. Anti-CD2 mAb and CTLA4Ig also inhibited interleukin (IL)-2, IL-4, and IL-2 receptor (CD25). These data indicate that anti-CD2 mAb plus CTLA4Ig induces hyporesponsiveness and tolerance. The mechanism is likely related to the initial disruption of independent pathways of T-lymphocyte activation leading to antigen-specific long-term graft survival.

Abatacept↗

Cochlear implantation in an intralabyrinthine acoustic neuroma patient after resection of an intracanalicular tumour.

This case study describes a therapeutic strategy using a cochlear implant for a bilateral acoustic neuroma deafened patient. The cochlear nerve had previously been sacrificed on one side during tumour removal, but on the remaining side a functioning cochlear nerve was assessed by electric promontory stimulation in spite of a neuroma extending into the vestibular labyrinth. The patient was successfully stimulated with a Nucleus 22-channel implant after removal of the intracanalicular portion of the neuroma via a middle fossa approach.

Cochlear Implants↗