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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 19 recordsLinked to original sources

Alternating non-cross-resistant chemotherapy for non-Hodgkin's lymphoma of intermediate-grade and high-grade malignancy. A pilot study.

Thirty-two patients with advanced non-Hodgkin's lymphoma (NHL) with aggressive histologic findings were treated with cyclophosphamide, doxorubicin, methotrexate with leucovorin rescue, bleomycin, vincristine, etoposide, ifosfamide, and prednisolone (CAMBO-VIP), in which presumably non-cross-resistant myelosuppressive and nonmyelosuppressive agents were administered during alternate weeks for 12 weeks. To ensure the high-dose intensity of the protocol, dose reduction and delay in treatment were minimized. Three patients were treated inadequately. Twenty-six (89.7%) of 29 evaluable patients had a complete response, and three had a good partial response. Relapse occurred in four patients, with a median follow-up of 29 months. The actuarial overall survival and disease-free survival were estimated to be 87.6% and 75.9%, respectively. The CAMBO-VIP treatment was well tolerated; myelosuppression was severe but transient and caused no serious infections. Side effects that affected dose intensity were oral ulceration, occurring in 28 patients, and blister formation under the thickened skin of palms and/or soles, followed by desquamation (5 patients). Hepatic toxicity was generally mild to moderate; it was severe in one patient. A 12-week regimen of CAMBO-VIP was effective for advanced NHL with aggressive histologic findings.

Adolescent

Factor XIII-dependent generation of 5th complement component(C5)-derived monocyte chemotactic factor coinciding with plasma clotting.

Blood coagulation or plasma clotting caused generation of a monocyte chemotactic factor(s) in vitro. The chemotactic factor, of which the apparent molecular mass was 75 kDa, shared antigenicity with complement C5 and possessed the affinity to monocytes, but not to polymorphonuclear leukocytes. The generation of the chemotactic factor was hindered in the presence of a thiol enzyme inhibitor, p-chloromercuriphenyl sulfonic acid, at the concentration of 1 mmol/l, although the gelation of plasma was apparently completed. Furthermore, the generation of chemotactic factor was not observed when a plasma deficient in blood coagulation factor XIII, which is a precursor of a thiol enzyme, plasma transglutaminase, was used; and the activity normally appeared when the deficient plasma was reconstituted with purified factor XIII or with a tissue transglutaminase prior to clotting. When the human sera were injected into guinea pig skin, the serum derived from normal plasma or from the reconstituted factor XIII deficient one caused mononuclear cell infiltration, however, the serum from the deficient plasma without reconstitution infiltrated to a significantly smaller extent. These results indicated that the complement system was initiated somehow during the clotting process resulting in the generation of the C5-derived monocyte chemotactic factor in cooperation with factor XIIIa (activated factor XIII).

Animals

Doppler echocardiographic measurement of cardiac output in man using mitral annulus method.

The mitral inflow method of measuring cardiac output with pulsed Doppler two-dimensional echocardiography was developed and validated against the thermodilution technique in 42 patients. A mitral inflow method combined the velocity of left ventricular inflow at the mitral annulus (apical long-axis view) with the cross-sectional area of the annulus calculated from its diameter (parasternal long-axis view). A good correlation was observed between thermodilution and Doppler measurements of cardiac output (r = 0.93). The ratio of Doppler measurements to thermodilution measurements will be between 0.76 and 1.15 for about 95% of cases. There was a good correlation between percentage change in thermal cardiac output and those in Doppler cardiac output (r = 0.95); the limits of agreement were -11.5% to 10.5%, suggesting that this method can be most useful for assessing relative changes in cardiac output.

Blood Flow Velocity

Natural Echinococcus multilocularis infection in a Norway rat, Rattus norvegicus, in southern Hokkaido, Japan.

Forty-two rats, Rattus norvegicus, captured at a garbage dump in southern Hokkaido, Japan, were examined, and one was found to be infected with Echinococcus multilocularis. The lesions were found in the liver, lung, mesenteric lymph nodes, greater omentum and also free in the abdominal cavity. No necrosis was observed in any of the lesions, and inflammatory reactions were mild. Protoscoleces were observed in the large liver cysts. A homogenate of these cysts, when transplanted into the abdominal cavity of three Mongolian gerbils and a rat, yielded numerous fully developed protoscoleces at 4-7 months post-inoculation. Judging from this, it is postulated that the rat could become a natural intermediate host for E. multilocularis in this area.

Animals

Biochemical switching device: biomimetic approach and application to neural network study.

There are many examples of enzymes that share substrates or cofactors in a cyclic manner. Techniques have been developed that use cyclic enzyme systems to assay quantitatively small amounts of biochemical substances (cofactor, substrate), however, only a few studies of the control of these systems have been published. The author previously showed with computer simulations that cyclic enzyme systems have the reliability of ON-OFF types of operation (McCulloch-Pitts' neuronic equation) capable of storing short-memory, and the applicability for a switching circuit in a biocomputer. This paper introduces a unique switching mechanism of cyclic enzyme system (basic switching element), and next, building the integrated biochemical switching system being composed of the basic switching element, shows the physiological phenomenon termed 'selective elimination of synapses' generally produced as a result of low-frequency train of electrical stimuli to the synapses (Kuroda, Y. 1989) Neurochem. Int. 14, 309-319).

Electric Stimulation

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

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

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