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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 667 records · Page 37Linked to original sources

Neuromuscular pharmacology in rat neonates: development of responsiveness to prototypic blocking and reversal drugs.

The neonatal pharmacology of neuromuscular drugs was studied in vivo in newborn rats and in vitro in neonatal phrenic nerve-hemidiaphragm preparations. Drugs used to probe neuromuscular development in rat neonates were physostigmine, edrophonium, neostigmine, 4-aminopyridine, d-tubocurarine (dTc), and succinylcholine. The prejunctional actions of these drugs were monitored in relation to neonatal age by the appearance of stimulus-evoked repetitive discharge initiated by motor nerve endings and the occurrence and magnitude of the resulting enhancement of twitch tension. The occurrence and incidence of drug-induced fasciculations also served to track the development of functional motor nerve endings. Each of these prejunctional actions was inoperative until the third neonatal week, indicative of incomplete motor nerve development. In contrast, 4-aminopyridine, a nonanticholinesterase, evoked these prejunctional actions in 1-wk-old rat neonates. Neostigmine and edrophonium antagonized dTc as early as the first week; presumably, postsynaptic maturation had reached a functional level. 4-Aminopyridine also antagonized dTc at week 1. Rat neonates showed resistance to dTc blockade when tested by neonatal phrenic nerve-hemidiaphragm preparations in vitro. Relationships between age and 85%-95% transmission block declined to the adult level by week 5. This result indicates that in rat neonates, pharmacodynamic rather than pharmacokinetic mechanisms predominate in the development of responsiveness to dTc.

4-Aminopyridine↗

[Preparation of phenyl treated packing materials for high-performance liquid chromatography: evaluation by retention behaviour of carbamazepine and diphenylhydantoin].

The retention behavior and selectivity of 30 kinds of phenyl-modified porous glasses and silicas, prepared from solutions of phenyldimethylchlorosilane, diphenylmethylchlorosilane or triphenylchlorosilane in xylene, were studied by high-performance liquid chromatography using carbamazepine and diphenylhydantoin as model compounds. From the elemental data for carbon, the maximum number of bonded phenyl groups per gram (mean pore diameter, 15 nm, specific surface area, 217 m2/g, pore volume, 0.85 ml/g) on the diphenyl-bonded glass surface was calculated to be 0.159 x 10(21). Using various acetonitrile-0.01 M potassium dihydrogen phosphate mixtures as eluents, carbamazepine and diphenylnydantoin were separated on all the gels studied, but the degrees of resolution of the two compounds were different. With an increase in specific surface area on the glasses or silicas, the k' values of the solute increased.

Carbamazepine↗

Tolerance to the convulsions induced by daily nicotine treatment in rats.

Development of tolerance to the nicotine-induced convulsions in rats was examined. Acute intraperitoneal (i.p.) administration of nicotine (2.5, 3.75 and 5 mg/kg) produced convulsions in a dose-dependent manner. Mecamylamine (1 mg/kg, i.p.) antagonized the convulsions, but hexamethonium (5 mg/kg, i.p.) did not modify them. Daily nicotine administration (2.5, 3.75 and 5 mg/kg, i.p.) once a day for 6 days developed tolerance to the convulsions induced by nicotine. After the daily administrations of nicotine for 6 days, the effects of a challenge administration of nicotine (2 mg/kg) on the nicotine-induced convulsions were tested on the 7th-day. Further tolerances were also developed by the 7th-day challenge administration. After the 7th-day test, nicotine levels of the brain and blood 15 min after the challenge injection were measured. With nicotine (5 mg/kg once a day)-treatment, nicotine levels of all the brain regions were increased. In contrast, a similar challenge injection had no effect on blood nicotine level. These results indicate that the development of tolerance to the nicotine-induced convulsions is produced relatively earlier and day by day by daily administrations to rats, which is closely related with the increase in brain nicotine level.

Animals↗

Effects of acute administration of nicotine on convulsive movements and blood levels of corticosterone in old rats.

The convulsive movements, blood levels of corticosterone and pharmacokinetics of nicotine after an acute intraperitoneal injection of nicotine (5 mg/kg) were examined in young (6-week-old) and old (2-year-old) rats. In pharmacokinetic study, blood nicotine levels during the elimination phase were significantly higher in old rats than in young rats. However, the duration of convulsions and the elevation of corticosterone levels after the nicotine injection showed significant decreases in old rats compared with those in young rats. These differences of nicotine-induced responses between young and old rats may be involved in the decrease in nicotine sensitivity.

Aging↗

[Fertilizing ability in vitro of golden hamster spermatozoa after acute testicular X-irradiation].

The present study is concerned with the effect of radiation to the testis on fertilizing ability in vitro using golden hamster spermatozoa. Male hamsters at 6 and 8 weeks of age were given acute testicular X-irradiation (200 kVp, 20 mA, 0.47-0.48 Gy/min). Spermatozoa were collected from the cauda epididymides at different times after irradiation and then they were suspended in fertilization medium. After preincubation for 4-5 hr, the spermatozoa were cultured with the eggs collected from mature hamsters treated with PMSG-hCG. Fertilized eggs were examined for incidence of sperm penetration and formation of pronuclei at 4-5 hr after insemination. The fertilization rate (47.7%) at the 6th week after irradiation with a dose of 2 Gy was much lower in comparison with the control value (92.6%). However, the fertilization rates at the 3rd and 9th weeks after irradiation were 97.7 and 90.6%, respectively. In these period, no difference was found between the irradiated groups and the control groups. From the changes in sperm concentration after irradiation with a dose of 2 Gy, it was found that the fertilization rate was the lowest at the 6th week. The sensitive stage to radiation during spermatogenesis with reference to the reduction of fertilizing ability after irradiation coincides with that of decrease in the sperm concentration and sperm motility. The results of fertilization rate at the 6th week after different doses of X-irradiation (0.25-6 Gy) indicated that the reduction of fertilization rate is nearly expressed as a dose-response relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal artery aneurysm: the significance of abdominal bruit and use of color Doppler.

A case of renal artery aneurysm is presented. The patient had no hypertension and no signs of arteriosclerosis obliterans or aortitis syndrome, except for abdominal bruit. A saccular aneurysm, 1 cm in diameter, was demonstrated by two-dimensional and color Doppler ultrasound and documented by angiography. The aneurysm was embolized by a steel coil. The abdominal bruit, though uncommon, is a very important bed-side sign of renal artery aneurysm, if the patient exhibits no arteriosclerosis obliterans or aortitis syndrome. Ultrasound Doppler is very useful in screening for aneurysm.

Aneurysm↗

Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.

Adult↗

[The effect of aging on observation in hearing in the same individuals over a 5 year period].

The purpose of this study was to investigate the process of changes in hearing of pure tones with aging. Among individuals who had undergone thorough medical examination for the purpose of annual health-checks, 293 males (586 ears) whose hearing level had been examined for five years or more were enrolled in this study. Cases having conductive deafness or known sensori-neural deafness were excluded. Since the most typical change with aging is observed at 8 kHz, the investigation was carried out only on hearing at 8 kHz. Hearing level increasingly declined with advancing age. Hearing distribution for young subjects showed a peak in the normal hearing level range. This peak decreased with aging, and another peak appeared at 50 dB. Investigation of differences in hearing in the individuals over the five years showed that most subjects had a hearing level difference of 0 dB up to 54 years of age. From 55 years old onward, however, the difference was 5 dB. This indicates that gradual deterioration of hearing level with aging occurs most frequently. On the other hand, in some subjects, deafness progressed faster. Thirty-four and a half percent of the subjects had deteriorations of 20 dB or more in a single year during the entire observation period. A deterioration of 20 dB or more was noted in 4% of the young and 8% of the elderly. Such rapid progression of deafness was believed to be involved in formation of the 50 dB peak in the hearing distribution.

Adult↗

WF11605, an antagonist of leukotriene B4 produced by a fungus. I. Producing strain, fermentation, isolation and biological activity.

WF11605, a new antagonist of leukotriene B4 (LTB4) was isolated as a product of fungal strain F11605. The molecular formula of WF11605 was determined to be C38H60O11. WF11605 inhibited LTB4-induced chemotaxis of rabbit polymorphonuclear leukocytes (PMNLs) with an IC50 value of 1.7 x 10(-7) M and blocked 3H-LTB4 binding to PMNL membranes at 5.6 x 10(-6) M (IC50). WF11605 also inhibited LTB4-induced degranulation of rabbit PMNLs at 3.0 x 10(-6) M (IC50). However, WF11605 did not show any inhibitory effect on platelet activating factor (PAF)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced degranulation at concentrations up to 10(-4) M. These results suggest that WF11605 is a specific antagonist of LTB4.

Animals↗

[A case report of postoperative recurrent hepatocellular carcinoma effectively treated with HCFU administration combined with TAE].

A 62-year-old man was found to have recurrent hepatocellular carcinoma (HCC) 2 cm in diameter in the left lobe in June 1990. After right lobectomy of the liver which contained the tumors of S6 2 cm and S8 3 cm in diameter 7 months before, the patient was treated with hepatic arterial embolization (TAE) combined with infusion of anti-cancer drug (ADM, CDDP) four times since June 1990. HCFU 300 mg per day was administered orally since June 1990. Since the 3rd TAE in December, 1990, the tumor stain in the left lobe disappeared for 10 months till October, 1991. No remarkable side effect of HCFU was noticed during this period. HCFU administration combined with TAE effectively prevented post-surgical recurrence of HCC in this case.

Antineoplastic Agents↗

[Recent progress in the chemotherapy program and its theoretical background--malignant lymphoma].

Recently developed third generation chemotherapy programs have improved long-term disease free survival of patients with non-Hodgkin's lymphoma of aggressive histology, as compared with their predecessors. These protocols have been developed based on the cancer chemotherapy principles derived mainly of experimental tumor studies by H. Skipper and his group, and the theoretical approach by Goldie and Coldman to the occurrence of and chemotherapeutic overcoming of resistant clones. They are characterized by the use of multiple non-cross-resistant drugs in maximally elevated dose intensity. Our third generation protocol, CAMBO-VIP, has produced 90% CR and 76% DFS at 3 years. Further improvement may be obtained by application of new drugs with different mechanism of action, effective means to destruct resistant cells, and further elevation of dose intensity by myelostimmulatory cytokines or transplantation of autologous/allogeneic peripheral blood or bone marrow stem cells.

Animals↗

[High-dose adjuvant chemotherapy with peripheral blood stem cell transplantation for breast cancer with poor prognosis--a pilot study].

Three patients with breast cancer with poor prognosis were treated with high-dose chemotherapy (HD-CT) and peripheral blood stem cell transplantation (PBSCT) as adjuvant treatment. After radical mastectomy, the consolidation chemotherapy with Adriamycin 50 mg/m2, Cyclophosphamide 1,000 mg/m2, Vincristine 1.0 mg/m2 and Methotrexate 200 mg/m2 with Leucovorin rescue was started. Recombinant human granulocyte colony stimulating factor (rhG-CSF) was also added for early recovery from myelosuppression. This combination chemotherapy was given every 3 weeks for 3 courses, and after the 2nd and 3rd courses, peripheral blood stem cells (PBSC) were collected and cryopreserved. HD-CT with Cyclophosphamide 2,000 mg/m2/day, Thio-TEPA 200 mg/m2/day, and Etoposide 300 mg/m2/day, were administered for 3 consecutive days, and after 48 hours of last doses, frozen-thawed PBSC (6.4-8.9 x 10(4)/kg of CFU-GM) were administered. rhG-CSF was also added. HD-CT and PBSCT were well tolerated, recovery from myelosuppression of the HD-CT was very quick and no serious side effects were observed.

Antineoplastic Combined Chemotherapy Protocols↗

[Hyperthermia for cancer with dextran magnetite using tubular implants].

Dextran magnetite particles (Meito Sangyo Corp.) are an aqueous magnetite zol and a nanometer complex consisting of dextran chains surrounding a core of ultrafine iron oxide. The tubular implants were made with polyester tube (3 mm diameter, 20 mm length) filled with DM aqueous zol (29%w/v). The temperature of an agar phantom with implants was measured in the inductive field. Heating was effected by creating an electromagnetic field with a 7 kW generator operating at 500kHz (Yamamoto Vinyter). The temperature was elevated 3.4 degrees at a distance of 5 mm from the implant at an inductive power of 2.6 kW. An area of 20 x 20 mm was heated while changing the power, the number of implants, and their arrangement. Selective heating of cancer was considered possible by inductive heating at 500 kHz and DM implants. Since the DM aqueous zol configuration can be readily changed, treatment of various cancers is possible.

Dextrans↗