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Biomedical subjects

T Ohtsubo

Publications and source records attributed to T Ohtsubo.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Efficacy of middle ear surgery for patients with hearing aids and middle ear disease].

Of 356 cases that underwent middle ear surgery for hearing improvement, 30 (8.4%) with air conduction hearing aids and middle ear disease were evaluated pre- and postoperatively. All surgeries were performed by the same surgeon. Diagnoses included 22 chronic otitis media, 5 chronic otitis media with cholesteatoma, 1 otosclerosis and 2 ossicular anomaly. Chief complaints at the first visit to Fukui Medical University Hospital were otorrhea (17 cases), hard of hearing (28 cases), dizziness (2 cases) and tinnitus (2 cases). Nineteen patients underwent surgery on both ears and eleven on one ear including five ears that showed better hearing preoperatively. Surgical procedures were tympanoplasty type I (15 cases), modified type III (8 cases), modified type IV (3 cases), stapedotomy (2 cases) and implantable hearing device (2 cases). After surgery, 16 patients (group 1) did not need hearing aids, while 14 (group 2) still needed hearing aids. Preoperative hearing was 64.1dB (n = 30) on average and average hearing one year after surgery in group 1 (35.4 +/- 14.1dB) was significantly better than in group 2 (58.1 +/- 18.4dB). After surgery, otorrhea stopped in all cases (100%), subjective hearing loss improved in 82% of the patients, vertigo improved in 100% and tinnitus improved in 50%. These results emphasize the benefits of surgical therapy, and the reasons why it should be recommended to patients with hearing aids and middle ear disease, such as to improve hearing disorders, to stop otorrhea and to prevent progressive sensorineural hearing loss.

Adolescent↗
PubMed1999

Thermosensitivity, incidence of apoptosis and accumulations of hsp72 and p53 proteins of murine L cells in wild type status of p53 gene.

Murine L cells showed markedly high lethal thermosensitivity. Survivals from fractionated heating at 44 degrees C with variety of interval time at 37 degrees C (44 degrees C for 10 min--variety of interval time at 37 degrees C-44 degrees C for 10 min) increased markedly in accordance with elongation of the internal time; i.e. survival fraction of 0.9% from 44 degrees C for 20 min alone without the interval time to those of 25% from the fractionated heating with interval time at 37 degrees C for 3-10 hrs. Incidence of apoptosis of the L cells from heating at 44 degrees C for 6.5 min (LD50) increased from 7% immediately after the heating to 30% 6-12 hrs after the post-incubation time at 37 degrees C. Accumulation of both hsp72 and p53 proteins markedly increased after a heating at 44 degrees C for 10 min alone in accordance with elongation of post-incubation time at 37 degrees C, representing a peak 6 hrs after the post incubation. Status of p53 gene in L cells were determined with Reverse Transcription-Polymerase Chain Reaction-Single Strand Conformational Polymorphism (RT-PCR-SSCP), i.e. wild type.

Animals↗
PubMed1998

Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells.

PURPOSE: The kinetics of the accumulation of inducible 72-kD heat shock protein (hsp72) and the activation of heat shock transcriptional factor (HSF) after hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172 having the wild-type p53 gene and T98G having the mutated p53 gene were evaluated. METHODS AND MATERIALS: Western blot analysis of hsp72, gel-mobility shift assay of HSF, cell survival, and development of thermotolerance were examined. RESULTS: The prominent suppression of heat-induced hsp72 accumulation by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53-dependent inhibition of heat-induced HSF activation by CDDP. The interactive hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but not in T98G cells. In addition, the heat-induced thermotolerance was suppressed by the presence of CDDP in the pretreatment. CONCLUSION: Suppression of heat-induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.

Antineoplastic Agents↗
PubMed1998

Molecular cloning of AtMMH, an Arabidopsis thaliana ortholog of the Escherichia coli mutM gene, and analysis of functional domains of its product.

We isolated and characterized cDNAs and a genomic clone encoding an Arabidopsis thaliana MutM homolog (AtMMH). AtMMH is a single-copy gene spanning about 3 kb in the nuclear genome, and comprises ten exons. The AtMMH gene encodes two types of mRNA (AtMMH-1 and AtMMH-2) formed by alternative splicing of exon 8. Western analysis of a crude extract from leaves of A. thaliana, using polyclonal antibodies against the recombinant proteins, demonstrated the presence in vivo of a single 44-kDa polypeptide that comigrates with the product of in vitro translation of the AtMMH-1 mRNA. AtMMH-1 protein prepared in vitro is able to nick double-stranded oligonucleotides containing 8-oxo-7,8-dihydroguanine (8-oxoG) and to bind such oligonucleotides, as does the Escherichia coli MutM protein, which possesses 8-oxoG DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities. Deletion of six amino acids (PELPEV), which are conserved among all known MutM homologs, from the N-terminal end of the AtMMH-1 protein abolishes its nicking but not its DNA-binding activity, indicating that these residues are essential for catalytic activity. Although the AtMMH-1 protein has a unique structure at its C-terminal end, which consists of alternating repeats of basic and acidic amino acids, this structure is dispensable for activity. However, the adjacent amino acid sequence (residues 268 to 281) is essential for repair activity.

Amino Acid Sequence↗
PubMed1998

Sensitization to hyperthermia by intracellular acidification of C6 glioma cells.

Hyperthermia has been introduced as a new modality of treatment for glioma. In these experiments, the cytotoxicity of hyperthermia in C6 glioma cells was enhanced by increasing the intracellular acidity with amiloride and/or 4,4'-diisothiocyanatostilbene-2,2' disulfonic acid (DIDS). Intracellular pH (pHi) is regulated mainly by Na+/H+ and HCO3-/Cl- antiports through the cell membrane, and amiloride acts on the former, DIDS on the latter to lower pHi. The cellular thermosensitivity to clinically achievable brain hyperthermia at 42 degrees C was enhanced by 0.5 mM amiloride (Na+/H+ antiport inhibitor). T0 values (T0 = the heating period required to reduce experimental survival rate by 1/e) at 42 degrees C without and with amiloride was 192 and 81 min, respectively. The addition of DIDS (HCO3-/Cl- antiport inhibitor) further enhanced. T0 value was 25 min. Fluorophotometric measurement of pHi was employed using the pH sensitive dye, bis(carboxyethyl)carboxyfluorescein, which is trapped in viable cells. The average pHi in control C6 glioma cells in pH 7.2 media was 7.21. In the untreated cells heated at 42 degrees C for 1 hour, the pHi was 7.12. The pHi of the cells heated in the presence of amiloride was decreased to 6.83. The pHi was further lowered to 6.67 by the treatment with amiloride in combination with DIDS for 2 hours. Hyperthermia with amiloride and DIDS may be a more effective treatment for malignant gliomas.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Suppression of heat-induced p53 accumulation and activation by CDDP or x-rays in human glioblastoma cells.

We showed that the prominent suppressions of heat-induced accumulation and activation of p53 by CDDP or X-rays were observed in A-172 cells, but not in T98G cells. In addition, the interactive hyperthermic enhancement of CDDP or X-ray cytotoxicity was observed in A-172 cells, but not in T98G cells. Our findings indicate that suppressions of heat-induced accumulation and activation of p53 by CDDP or X-rays contribute positively to an interactive hyperthermic enhancement of CDDP- or X-ray cytotoxicity.

Antineoplastic Agents↗
PubMed1998

Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors.

UNLABELLED: To determine whether PET could help differentiate malignant from benign thyroid tumors, 18F-fluorodeoxyglucose (FDG) accumulation and 201Tl scintigraphy were examined relative to histological diagnosis. METHODS: Nodular thyroid lesions in 11 patients were evaluated before surgical resection. Static PET scanning with 370 MBq FDG was done for 20 min (from 40 to 60 min postinjection) in all patients, and standardized uptake values (SUVs) in these lesions were calculated. In addition, eight patients were evaluated with dynamic PET scan up to 60 min postinjection, and the lesions were further evaluated using graphical analysis. Thallium-201 delayed images were visually evaluated in 10 patients. RESULTS: Four of 11 nodules were well-differentiated papillary carcinoma, another five were benign follicular adenomas, one was a multinodular goiter and another a case of chronic thyroiditis that was proved not to contain a nodule. Time-activity curves of FDG uptake showed different patterns in malignant and benign tumors. In the malignant tumors, FDG uptake increased with time after the tracer injection. By contrast, FDG uptake in benign tumors gradually decreased. With use of a cutoff value of 5.0 mg/ml for SUV and 10 microl x min(-1) x ml(-1) for Kc (K complex value determined using the linear fitting of the time-activity curve of FDG accumulation), all of the four malignant nodules and the six benign nodules were separated correctly. Chronic thyroiditis had high SUV in the malignant range. Of the four patients with thyroid carcinoma, the delayed 201Tl images revealed a slightly higher or equal uptake to background activity. In a patient with chronic thyroiditis, the delayed 201Tl images revealed diffuse accumulation higher than background activity. CONCLUSION: FDG-PET is superior to 201Tl in differentiating malignant from benign tumors. Both SUVs and Kc values were useful indexes for this discrimination. Although careful evaluation is needed for chronic inflammatory lesions, this technique appears to be useful in evaluating thyroid nodules.

Adenoma↗
PubMed1997

p53-dependent induction of WAF1 by a low-pH culture condition in human glioblastoma cells.

The effects of an acidic condition (pH 6.5) on WAF1 gene expression and p53 accumulation was investigated in human glioblastoma cells with different p53 statuses. WAF1 and p53 accumulation after treatment in acidic conditions was observed in A-172 cells carrying the wild-type p53 gene but not in T98G cells carrying the mutant p53 gene. Northern blot analysis showed that WAF1 gene activation by acidic conditions only occurred in A-172 cells. Consistent with this, activation of the binding of p53 to its specific DNA sequence by acidic stress was detected by gel mobility shift assay using p53 consensus sequence as a probe. Moreover, the increased WAF1 protein and mRNA levels that were due to acidic treatment returned to normal levels upon the return of the cells to neutral conditions, 6 h after the cells had been cultured in acidic conditions for 6 or 12 h. These findings suggest that WAF1 gene activation is inducible by acidic conditions in human glioblastoma cells, which is probably due to activation of the p53-dependent signal transduction pathway.

Cyclin-Dependent Kinase Inhibitor p21↗
PubMed1997

Expression of P-glycoprotein in inner ear capillary endothelial cells of the guinea pig with special reference to blood-inner ear barrier.

Expression of P-glycoprotein (P-gp) was detected immunohistochemically in the guinea pig inner ear using mouse anti-P-gp monoclonal antibody C219. P-gp was found only in the capillary endothelial cells of the cochlea and vestibule. The pattern of P-gp immunostaining in the inner ear was similar to that of the brain. The present investigation suggested that P-gp expression in inner ear capillary endothelial cells might play an important role in the blood-inner ear barrier by acting as an extrusion pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

P-glycoprotein expression in capillary endothelial cells of the 7th and 8th nerves of guinea pig in relation to blood-nerve barrier sites.

Expression of P-glycoprotein (P-gp) was detected by immunohistochemical staining and Western blot analysis in the peripheral nerves (7th and 8th nerves) of the guinea pig using anti-P-gp monoclonal antibody C219. P-gp was detected in the capillary endothelial cells of these nerves. Immunoreactivity in these nerves was similar to that in the brain. Besides these nerves, positive staining was observed in the sciatic nerve, although immunoreactivity was somewhat lower than that of the 7th and 8th nerves. The present investigation suggested that P-gp in the endothelial cells of the peripheral nerves might play a very important role as a part of the blood-nerve barrier function, since P-ag acts as an extension pump in these cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

The effect of sodium thiosulfate on ototoxicity and pharmacokinetics after cisplatin treatment in guinea pigs.

The effect of sodium thiosulfate (STS) on the pharmacokinetics and ototoxicity of cisplatin (CDDP) was investigated in guinea pigs. Animals received three intramuscular injections of 7.5 mg/kg CDDP separated by intervals of 5 days with or without STS (1,000 mg/kg) administered intraperitoneally immediately and 1 h after each injection of CDDP or 3 and 6 h later. When administered alone, CDDP caused total outer hair cell (OHC) loss in the basal and second turns of the cochlea. In the group administered CDDP and STS, damage to the OHCs was mild when STS was given concurrently, but was severe when STS was given 3 and 6 h later. Pharmacokinetics measured as free and total platinum (Pt) concentrations in plasma and total Pt concentration in perilymph was not affected after administration of STS with CDDP. These results suggest that an inactive Pt-thiosulfate complex is formed in plasma and is measured as a free Pt component which enters the perilymph via the blood-cochlear barrier. Two possible mechanisms are proposed by which STS reduces ototoxicity: entry of CDDP into target cells such as OHCs and strial marginal cells or binding to intracellular macromolecules of these cells is prevented.

Animals↗
PubMed1997

A xanthanolide with potent antibacterial activity against methicillin-resistant Staphylococcus aureus.

This study was conducted to find constituents of an annual herb, Xanthium sibiricum Patr er Widd, with effective antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). By monitoring antibacterial activity against MRSA strains, it was shown that a sesquiterpene lactone, identified as [3aR-(3a alpha, 7 beta,8a beta)]-3,3a,4,7,8,8a-hexahydro-7- methyl-3-methylene-6-(3-oxo-1-butenyl)-2H-cyclohepta[b]furan-2-one, or xanthatin, isolated from leaves of the herb, had outstandingly potent activity against S. aureus species, including MRSA; its activity against MRSA and MSSA strains was similar. Other bacteria, e.g. Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa and Salmonella typhi, were also susceptible at the concentrations tested but the compound had no inhibitory effect on some other bacteria, including Escherichia coli. The results show that xanthatin has outstandingly potent activity against strains of S. aureus but that the activity of the compound is highly species-specific.

Anti-Bacterial Agents↗
PubMed1997

Extraction and purification of effective antimicrobial constituents of Terminalia chebula RETS. against methicillin-resistant Staphylococcus aureus.

Examination of the EtOH extract of the fruiting bodies of Terminalia chebula RETZ. led to the isolation of two potent antimicrobial substances against even methicillin-resistant strains of Staphylococcus aureus. On the basis of spectroscopic evidence, the two isolates have been identified as gallic acid and its ethyl ester.

Anti-Bacterial Agents↗
PubMed1997

The effects of combined treatments with low hyperthermia and bleomycin on survivals of murine L cells.

Modification effects of low hyperthermia (40 degrees C) on cellular chemosensitivity to bleomycin (BLM), and of BLM on thermosensitivity (40 degrees C) were investigated in cultured murine L cells with simultaneous or sequential treatments of these two agents. The heating of L cells at 40 degrees C up to 6 hours resulted in no remarkable lethal damage. Treatment with low hyperthermia followed by BLM for 4 hours showed no more than additive effect. However, a significant chemical (BLM) enhancement effect on the cellular thermosensitivity was observed by the treatment with BLM for 4 hours prior to the low hyperthermia at 40 degrees C. No appreciable thermal enhancement effect on the cellular chemosensitivity to BLM was shown by preheating at 40 degrees C for 3 hours, while post-heating at 40 degrees C showed a significant thermal enhancement effect as well as in the simultaneous treatments. The cell phase response to BLM was levelled in the clinical range of the doses. It is possible that the repair of sublethal damage (SLDR) from treatment with BLM was inhibited by 40 degrees C post-heating and this SLDR was completed at 3 hours of the interval at 37 degrees C between BLM and 40 degrees C heating.

Animals↗
PubMed1996

Suppression of heat-induced hsp72 accumulation by cisplatin in human glioblastoma cells.

The accumulation of the inducible hsp72 (72-kDa heat shock protein) after hyperthermia and/or cisplatin treatment in human glioblastoma cell line (A-172) was studied by Western blot analysis. The level of hsp72 increased to eight-fold 10 h after hyperthermia alone (44 degrees C for 20 min, D50) and to three-fold 10 h after cisplatin treatment (5 microg/ml) at 37 degrees C for 15 min (D50). In contrast, when the cells were simultaneously heated with cisplatin, the accumulation of hsp72 was suppressed. The level of hsp72 increased to about six-fold and two-fold 10 h after hyperthermia (44 degrees C, 15 min) in the presence of 1 and 10 microg/ml (D50 or D10) of cisplatin, respectively. In addition, we found both the enhancement of thermosensitivity and the suppression of thermotolerance by the simultaneously combined treatment of hyperthermia and cisplatin. It has been reported that the enhancement of cisplatin cytotoxicity by hyperthermia is due to increase of both cisplatin uptake and DNA damage by hyperthermia. Our results suggest that the interactive cytotoxic enhancement by the combination of hyperthermia and cisplatin may be also due to the suppression of heat-induced hsp72 accumulation by cisplatin.

Antineoplastic Agents↗
PubMed1996

Prevention of persistent ear drum perforation after long-term ventilation tube treatment for otitis media with effusion in children.

The effect of tape patch technique using Steri-Strip tape in combination with freshening of the perforation edge after removal of long-term ventilation tubes for preventing permanent ear drum perforation was evaluated. The longer the tubes remained in place, the higher the incidence of persistent perforation after tube removal. The perforation rate after Goode T-tube treatment was 4.0% in the spontaneous extrusion group and 14.3% in the intentional removal group. In the ears treated by tape patch application, none of the perforations persisted after removal of the Goode T-tube. After removal or extrusion of Paparella Type II tube, perforations did not close in 13.2% of the group without tape patch application. When a tape patch was applied, only one perforation (3.3%) did not close. From these results, tape patch technique in combinations with freshening of the perforation edge at the time of tube removal was useful to promote healing and prevent persistent ear drum perforation.

Chi-Square Distribution↗