Search PubMed⌕ Search

Biomedical subjects

M Nishio

Publications and source records attributed to M Nishio.

At least 217 records · Page 12Linked to original sources
PubMed1993

Ca(2+)- and Na(+)-dependent depolarization induced by maitotoxin in the crayfish giant axon.

1. Maitotoxin (MTX) depolarized the membrane of the crayfish giant axon and decreased the amplitude and maximum rate of rise of action potentials in an irreversible manner. 2. The depolarizing action of MTX was attenuated in low Ca (1 mM; 1/10 of normal concentration) solution and was also inhibited by 2 mM Co2+, 300 microM Ni/+, 1 microM nifedipine, 10 microM verapamil or 1 microM tetrodotoxin. 3. These results suggest that the depolarization by MTX in the crayfish giant axon may be related to changes not only in Ca permeability but also in Na permeability, possibly through the modification of existing Na or Ca channels and/or a new type of channel or pore induced by MTX.

Action Potentials↗
PubMed1993

Results of cesium needle interstitial implantation for carcinoma of the oral tongue.

One hundred thirty previously untreated patients with invasive squamous cell carcinoma of the oral tongue received interstitial radiotherapy with curative intent using cesium needles. Ninety-nine patients were treated with interstitial radiotherapy alone and 31 patients received interstitial radiotherapy combined with external beam irradiation. The recurrence-free rates in the primary lesions were 94.4% (17/18) in T1, 91.2% (52/57) in T2, and 70.9% (22/31) in T3 lesions. The local recurrence-free rates with single-plane and two-plane implantation were good: 89.7% (70/78) and 85.7% (12/14), respectively. The rate of 64.2% (9/14) for volume implantation was significantly poorer (p < 0.05). It is evident that tumor volume is an important factor in the control of cancer following interstitial therapy. The overall incidence of ulceration of the tongue and mandibular complication was 20% (26/130) and 13% (17/130), respectively. Using both interstitial and external radiotherapy, the incidence was 22.5%, compared with 10.1% using interstitial radiotherapy alone. The mandibular complication incidence of 8.9% with single-plane implants was much lower than 20.8% for two-plane and 23.5% for volume implants. Interstitial radiotherapy is most suitable in T1 and T2 cases in which single-plane implantation is possible; for these patients interstitial radiotherapy, which has the advantage of preserving the structure and function of the tongue, should continue to be used in the future in spite of the progress in reconstructive surgery.

Adult↗
PubMed1993

Dopamine D2 and serotonin S2 receptors in susceptibility to methamphetamine psychosis detected by positron emission tomography.

Positron emission tomography (PET) was used to assess the role of dopamine D2 receptors in the striatum and serotonin S2 receptors in the frontal cortex in the susceptibility to methamphetamine-induced psychosis. Subjects were six men who had previously experienced methamphetamine psychosis (methamphetamine subjects) and 10 age- and sex-matched control subjects. The radiotracer used was 11C-N-methylspiperone. Although binding availability, assessed by dynamic analysis, in the two regions did not differ between the two groups, the ratio of binding availability in the striatum to that in the frontal cortex significantly decreased in the methamphetamine subjects as compared with the control subjects. These findings suggest that an imbalance in the activity of these two receptors may be related to the susceptibility to methamphetamine psychosis.

Adult↗
PubMed1993

Characterisation of a vindesine-resistant human small-cell lung cancer cell line.

We established a vindesine-resistant (x 11.6) human small-cell lung cancer cell line (H69/VDS) by stepwise exposure of parent line H69 to vindesine. H69/VDS showed cross-resistance to taxol (x 10.1), vincristine (x 6.9) and colchicine (x 3.4) but not to doxorubicin, cisplatin or etoposide. There was no significant difference in intracellular [3H]-vincristine and doxorubicin accumulation between H69 and H69/VDS cells. The human mdr1 mRNA was not detected in either of the cell lines. These results indicated that H69/VDS did not express a typical multidrug resistant phenotype. Addition of 20 microM verapamil enhanced the growth inhibitory effect of vindesine on both H69/VDS (x 12.0) and H69 cells (x 3.8). The amount of total tubulin in H69/VDS cells was lower than that in the H69 parental cells. No significant increase was observed in the amount of total and polymerised tubulins of H69 cells. In H69/VDS cells, however, verapamil increased the amount of total tubulin to the level of parental cells, but decreased the amount of polymerised tubulin. Modulation of tubulin may play a role in the resistance to vindesine.

Antineoplastic Agents↗
PubMed1993

Sequence determination of the P gene of simian virus 41: presence of irregular deletions near the RNA-editing sites of paramyxoviruses.

The complete nucleotide sequence of the P gene of simian virus 41 (SV41) was determined. The gene was found to be 1406 nucleotides long and to contain a relatively small open reading frame encoding a cysteine-rich V protein with a calculated M(r) of 24076. We have demonstrated that RNA-editing events occur in SV41 P gene transcripts and that the ratio of edited mRNAs to faithfully copied mRNA (P-mRNA:V-mRNA) is about 1:5 at either 24 or 40 h post-infection. The mRNA with two G insertions was capable of encoding a P protein of 395 amino acids with a predicted M(r) of 41,992. A kinetic study of P and V proteins by Western blot analysis showed that in virus-infected cells the amounts of both proteins were almost equal although the V-mRNA was considerably more abundant than the P-mRNA. Alignment of the SV41 P and V proteins with those of nine other paramyxoviruses demonstrated that irregular gaps were present around the RNA-editing sites.

Amino Acid Sequence↗
PubMed1993

The influence of light drowsiness on the latency and amplitude of P300.

Light drowsiness affected the P300 obtained with a standard auditory oddball paradigm. A simple two-tone discrimination paradigm was used. The frequent nontarget stimuli were 1000 Hz pure tones and the infrequent target stimuli were 2000 Hz pure tones. The subjects were required to press a button whenever infrequent target tones were presented. With light drowsiness, P300 increased in latency and decreased in amplitude, but the counts of infrequent tones remained correct nevertheless. It was concluded that electrophysiological brain function differs in the light drowsy and awake states. In studies on P300, it is essential to rule out light drowsiness to obtain valid P300 amplitudes and latencies.

Adult↗
PubMed1993

Phase I study of CPT-11 and etoposide in patients with refractory solid tumors.

PURPOSE: To determine the maximum-tolerated dose (MTD) and acceptable dose level of a cytotoxic regimen of CPT-11, a new camptothecin derivative, in combination with etoposide (VP-16) and to describe the principal toxicities associated with it. PATIENTS AND METHODS: Patients with refractory solid tumors received VP-16 and CPT-11 daily for 3 consecutive days (days 1 through 3) every 3 or 4 weeks. Groups entered the trial at escalating CPT-11/VP-16 dose levels of 40/60, 60/60, 60/80, and 80/60 mg/m2. Thirty-four patients entered this study, of whom 33 were assessable for toxicity and 22 for therapeutic efficacy. RESULTS: Granulocytopenia was so severe that this regimen required supportive therapy with recombinant human granulocyte colony-stimulating factor (G-CSF). The majority of the patients experienced a 5% weight loss and diarrhea was the dose-limiting toxicity. The MTDs were 60/80 and 80/60 mg/m2 administered on days 1 through 3. Five of seven previously untreated patients with non-small-cell lung cancer (NSCLC) achieved partial responses (PRs) to this therapy, as did two with NSCLC who had received prior chemotherapy, two with head and neck cancer, and one with an adenocarcinoma (primary tumor unknown). CONCLUSION: The recommended dose of CPT-11/VP-16 for this regimen with G-CSF is 60/60 mg/m2 on days 1 through 3 every 3 to 4 weeks. We suggest that the combination of topoisomerase I and II inhibitors is likely to be an effective treatment strategy. The activity of this regimen against NSCLC is particularly encouraging and should be evaluated in a phase II trial.

Adult↗
PubMed1993

[A case of middle ear carcinoma with high plasma G-CSF level].

Malignant tumors sometimes yield a variety of paraneoplastic syndrome. We report a case of middle ear cancer demonstrating unusual granulocytosis which was considered to belong to this syndrome. A patient, 67-year-old male, noticed left facial nerve palsy in June 1989, and was operated on under the diagnosis of chronic otitis media. However, middle ear tumor was suspected during the operation, which was confirmed to be squamous cell carcinoma. He was referred to our hospital for radiotherapy. Six months after irradiation, spontaneous liqorrhea due to the dural necrosis occurred. When intracranial repair of dura was performed, tumor invasion into the dura was noticed. Subtotal resection of the temporal bone with iridium implant was done in vain to control the recurrent tumor, which spread quickly to adjacent tissues. A month before the death, progressive granulocytosis without appreciable inflammatory signs started. Numbers of WBC rapidly increased, maximally reaching 88,300/cmm. Plasma G-CSF concentration was assayed at this time, showing about ten times as much as that of normal controls. It was thus postulated that production of this substance by the tumor was responsible for granulocytosis.

Aged↗
PubMed1993

Synthesis and antifungal activity of pradimicin derivatives. Modifications on the aglycone part.

Synthesis and antifungal activity of pradimicin analogs modified on the aglycone part is described. Upon modification studies at various sites of the aglycone part using pradimicin A (PRM A), C-11 position was found to be the sole site to be modified without loosing antifungal activity. Further modification studies at C-11 position were carried out with 11-OH derivative of pradimicin T1 (PRM T1) because of its easy availability. Among the compounds prepared, 11-demethoxy derivative of PRM A (12) and 11-O-ethyl (13) and 11-O-fluoroethyl (14) derivatives of PRM T1 showed promising antifungal activity comparable to that of PRM A.

Antibiotics, Antineoplastic↗
PubMed1993

Studies on the mode of antifungal action of pradimicin antibiotics. II. D-mannopyranoside-binding site and calcium-binding site.

Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.

Anthracyclines↗
PubMed1993

Synthesis and antifungal activities of pradimicin A derivatives modification of the alanine moiety.

Chemical modifications of the carboxyl group in the alanine moiety of pradimicin A were performed and in vitro and in vivo antifungal activities of the derivatives were examined in comparison with those of pradimicin A. The amide derivatives showed activities comparable to pradimicin A, indicating that the free carboxyl group can be modified without impairing the antifungal activity.

Alanine↗
PubMed1993

Calcium channel current in cultured rat mesangial cells.

The presence of voltage-dependent calcium channels has been suggested in mesangial cells by using calcium-sensitive fluorescent probes. However, direct electrophysiological evidence for voltage-dependent calcium channels has not yet been presented. In this study voltage-dependent calcium channels were studied in cultured rat mesangial cells. Whole-cell patch-clamp experiments were done with 50 mM Ba2+ as a charge carrier. Step depolarizing pulses from a holding potential of -50 mV produced an inward barium current at potentials more positive than -10 mV, and a peak current (10-45 pA) was obtained at a membrane potential of approximately +30 mV. The inward current was augmented by 100 nM Bay K 8644, attenuated by 1 microM nifedipine, and abolished by 50 microM Cd2+. These results indicate that the inward current is a barium current flowing through L-type calcium channels. This may be the first study that demonstrates the presence of L-type calcium channels in mesangial cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Pharmacokinetic re-evaluation and phase I study of high dose epirubicin in advanced non-small cell lung cancer.

We performed a phase I trial to evaluate the toxicity and the maximum tolerated dose of high dose epirubicin on a three-consecutive-day schedule on Japanese patients with advanced non-small cell lung cancer. Fourteen patients were entered in the study. At least three patients were assigned to each different dose level. Epirubicin was given intravenously daily for three day by bolus injection. The dose was started at 60 mg/m2/course and escalated by 30 mg/m2/course. Granulocytopenia was found to be the dose limiting toxicity with a maximum tolerated dose of 150 mg/m2/course. Thrombocytopenia and non-hematological toxicities were mild and well tolerated. The maximum tolerated dose was lower than that in Europe and Canada. Partial responses were observed in two out of five patients on 150 mg/m2/course. The recommended phase II dose for high dose epirubicin was demonstrated to be 120 mg/m2/course. A further dose-escalating study of epirubicin in conjunction with the administration of granulocyte colony stimulating factor is scheduled for the determination of its antitumor activity in non-small cell lung cancer.

Adult↗
PubMed1993

[Effects of aerosol oxitropium bromide and fenoterol on maximal exercise capacity in chronic obstructive pulmonary disease and their correlation with air flow during exercise and with parameters of maximal exercise].

To examine the effects of bronchodilators on maximal exercise capacity and their correlation with airflow during exercise in patients with chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized comparison between inhaled fenoterol (beta 2-agonist) and oxitropium bromide (anticholinergic agent) in 8 patients with stable COPD (mean age 73 years, mean FEV1 1.1 L, mean FEV1% 50%). Only oxitropium bromide resulted in statistically significant improvement in FEV1 40 min after inhalation. On maximal exercise, fenoterol did not affect oxygen uptake (VO2 max), minute ventilation (VEmax), respiratory frequency (Rfmax), ventilatory efficacy (VEmax/VO2 max), peak expiratory flow during exercise (PEFmax), heart rate (HRmax) and dyspnea (Borg Scale Slope). After oxitropium bromide, dyspnea during exercise and HRmax decreased significantly, but PEFmax and other parameters did not change significantly compared with control. There was no correlation between changes in dyspnea during exercise and changes in FEV1 and PEFmax after oxitropium bromide inhalation. We conclude that inhaled oxitropium bromide, an anticholinergic agent, reduces dyspnea during exercise in patients with COPD. This favorable effect was not due to change of airflow limitation during exercise, and other factors can thus influence reduction of dyspnea during exercise in these patients.

Administration, Inhalation↗