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Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 1,081 records · Page 60Linked to original sources

Determination of diazepam and its pharmacologically active metabolites in blood by bond Elut column extraction and reversed-phase high-performance liquid chromatography.

A rapid and quantitative analytical micro method for the determination of diazepam and its major pharmacologically active metabolites utilizing high-performance liquid chromatography (HPLC) is reported. The drug and its metabolites were extracted from 50-100 microliter samples of whole blood, serum or plasma using Bond Elut C 18 column and quantitated by high-performance liquid chromatography, using Technician Fast-LC-C-8 (RP 5 micrometers) bonded column and a mobile phase consisting of 53% methanol, 1% acetonitrile in KH2PO4 buffer and 10 microliters/l triethylamine. Methyl nitrazepam and medazepam were used as internal and external standards respectively. The extraction and recovery of diazepam and its major pharmacologically active metabolites, i.e., 3-hydroxydiazepam, desmethyldiazepam and oxazepam from blood were higher than 88% for all compounds. The minimum detection range of each compound was approximately 2.5 ng per 100-microliter sample. This micro method of simultaneous quantitation of diazepam and its major pharmacologically active metabolites provides a valuable technique for the study of diazepam pharmacokinetics in a small animal model without disturbance of normal hemodynamics from excess blood loss, as well as in clinical evaluation of pediatric patients.

Chromatography, High Pressure Liquid↗

Lithium toxicology: effect of isotopic composition on lethality and behavior.

Naturally occurring lithium consists largely of the stable lithium-7 isotope but it contains 7.6% of a second stable isotope, lithium-6. Biological effects of these two isotopes were not identical. When administered in isotopically pure form, the chloride of lithium-6 was more toxic after acute intake than the chloride of pure lithium-7:its LD in Swiss-Webster mice was 13.2 mEq/kg as opposed to 15.9 mEq/kg for the salt of the heavier isotope and 14.9 mEq/kg for that of the natural mixture of the two isotopes. A single injection of one or the other pure isotope in a constant dose, 14.5 mEq/kg led to a 90% mortality in mice given lithium-6 but only 10% in mice given lithium-7. Side effects such as hypoactivity, ataxia, intense perspiration and diarrhea appeared within 10 min after administration of toxic doses of lithium-6 but more gradually after lithium-7. The differences between the isotopes in toxicity and rate of appearance of effects on spontaneous motor activity were significant at the p less than 1% level.

Animals↗

Induction of Bacillus subtilis sporulation by decoyinine and the concomitant disappearance of ppGpp in vegetative cells.

Sporulation of Bacillus subtilis, growing exponentially in the presence of rapidly metabolizable nutrients, was induced by addition of decoyinine (an antibiotic inhibitor of GMP synthesis), and intracellular amounts of ppGpp were determined after 2 M formic acid extraction by polyethyleneimine (PEI)-cellulose thin-layer chromatography. Consequently, it was found that the ppGpp in vegetative cells abruptly disappeared after the addition of decoyinine. This indicates that the disappearance of ppGpp is closely correlated to the initiation of B. subtilis sporulation.

Adenosine↗

Stimulatory effect of cytochrome b5 induced by p-nitroanisole and diisopropyl 1,3-dithiol-2-ylidenemalonate on rat liver microsomal drug hydroxylations.

The relationship between the changes in the amount of the components of the liver microsomal electron transport systems and drug hydroxylase activities on administration of p-nitroanisole was investigated. The content of cytochrome P-450 in the p-nitroanisole-treated rats was not significantly different from that in the controls during the treatment. The cytochrome b5 content increased 2.2-fold over that of the controls after 14 days of treatment. Demethylation activities per mg microsomal protein of p-nitroanisole, aminopyrine, and benzphetamine were enhanced 2.7-, 2.4-, and 2.8-fold, respectively, but aniline hydroxylase activity was not enhanced. Similar results were obtained with microsomes from diisopropyl 1,3-dithiol-2-ylidenemalonate (NKK-105)-treated rats. The time-course study of changes in the amount of the components of drug hydroxylase systems suggested that the increase in cytochrome b5 content enhanced the demethylation activities. In the reconstituted system containing cytochrome P-450 partially purified from p-nitroanisole- or NKK-105-treated rats, cytochrome b5 was required for the maximal activities of the demethylation reactions, but did not participate in aniline hydroxylation. These findings showed good correlation between the change of cytochrome b5 content and the demethylation activities and suggested that the increase in cytochrome b5 content might enhance the demethylation activity by stimulating supply of a second electron to cytochrome P-450.

Animals↗

A myofibrillar component that modifies the actin-myosin interaction in postrigor skeletal muscle.

A protein component that modified the interaction between actin and myosin was released from myofibrils on Ca2+-treatment, accompanying the weakening of Z disks. For its release 10(-4) M Ca2+ was required. The presence of the component facilitated the dissociation of thin and thick filaments from myofibrils and delayed superprecipitation of reconstituted actomyosin, independently of Ca2+ concentration. The component is probably a constituent of Z disks. In postmortem muscle, it is possible that the component is released from Z disks with an increased concentration of Ca2+, and that it weakens rigor linkages formed between actin and myosin, giving rise to lengthening of rigor-shortened sarcomeres.

Actins↗

Enzymic mechanism of starch breakdown in germinating rice seeds : 11. Ultrastructural changes in scutellar epithelium.

The ultrastructural changes occurring in the scutellar epithelium cells of rice seeds have been studied during germination and early seedling growth. During this time, several prominent structural changes occur, including (a) formation, development, and proliferation of organelles such as mitochondria, rough endoplasmic reticulum, free ribosomes, and Golgi apparatus; (b) folded structural modification of plasmamembranes in later stages; and (c) conspicuous decrease in lipid-storing spherosomes. Glyoxysome-like electron dense particles are detectable but their formation is much less prominent. It is conceivable that all these structural changes are related to the enhancement of the metabolic activities of the epithelial cells including the synthesis of hydrolytic enzymes such as alpha-amylase and their secretion into the endosperm tissues. Some enzyme activities characteristic of mitochondria and glyoxysomes have been determined using the crude scutellar extracts, and the results dealing with the low activities of the glyoxylate cycle enzymes and palmitoyl-coenzyme A oxidase appear to indicate that fatty acid breakdown is possibly via mitochondrial beta-oxidation, although we reserve a definitive conclusion on the glyoxysomes being nonfunctional in fatty acid oxidation in rice seedlings.

Journal Article↗

Localisation and direction of mitral regurgitant flow in mitral orifice studied with combined use of ultrasonic pulsed Doppler technique and two dimensional echocardiography.

Regurgitant flow was analysed in 40 cases of mitral regurgitation, using combined ultrasonic pulsed Doppler technique and two dimensional echocardiography. Abnormal Doppler signals indicative of mitral regurgitant flow were detected in reference to the two dimensional image of the long axis view of the heart and the short axis view at the level of the mitral orifice. The overall direction of regurgitant flow into the left atrium was clearly seen in 28 of 40 cases, and the localisation of regurgitant flow in the mitral orifice in 38 cases. In cases with mitral valve prolapse of the anterior leaflet or posterior leaflet the regurgitant flow was directed posteriorly or anteriorly, respectively. The prolapse occurred at the anterolateral commissure or posteromedial commissure and resulted in regurgitant flow located near the anterolateral commissure or posteromedial commissure of the mitral orifice, respectively. In cases with rheumatic mitral regurgitation the regurgitant flow is usually towards the central portion of the left atrium and is sited in the mid-part of the orifice. The Doppler findings were consistent with left ventriculography and surgical findings. The ultrasonic pulsed Doppler technique combined with two dimensional echocardiography is useful for non-invasive analysis and preoperative assessment of mitral regurgitation.

Adult↗

Pulmonary regurgitation studied with the ultrasonic pulsed Doppler technique.

Sixty patients with pulmonary regurgitation were studied by the pulsed Doppler technique combined with two-dimensional and M-mode echocardiography. Patients with pulmonary regurgitation had abnormal Doppler signals just below the pulmonic valve in the right ventricular outflow tract in diastole on the two-dimensional image. These signals were considered to indicate the regurgitant flow. There are two patterns of pulmonary regurgitant Doppler signals. In pulmonary hypertension, the maximal component of instantaneous flow velocity is sustained at about the same signal strength throughout diastole, but when the pulmonary arterial pressure is normal, the velocity slows down gradually from early diastole to end-diastole. Pulmonary regurgitation was detected by phonocardiography in about half the patients. In the remaining half, pulmonary regurgitant murmur could not be differentiated from aortic regurgitant murmur or was masked by coexistent aortic regurgitation or patent ductus arteriosus, whereas the Doppler technique indicated pulmonary regurgitation.

Adolescent↗

Evaluation of tricuspid regurgitation by pulsed Doppler and two-dimensional echocardiography.

We analyzed tricuspid regurgitation noninvasively using ultrasonic pulsed Doppler and two-dimensional echocardiography in 66 patients in whom tricuspid regurgitation was suspected from routine clinical evaluation. All of the patients also underwent right ventriculography. Ten healthy subjects served as controls. In 62 of 66 patients, the study was adequately performed. In 58 of 62 patients, pansystolic abnormal Doppler signals were detected in the right atrial cavity, and were interpreted to indicate tricuspid regurgitant flow. Two-dimensional echocardiograms in the parasternal four-chamber view demonstrated that the region in which the abnormal Doppler signals were detected was spindle-shaped and extended from the tricuspid orifice toward the right atrial posterior wall parallel to the interatrial septum. The severity of regurgitation was graded on a four-point scale, based on the distance reached by the abnormal signals from the tricuspid orifice toward the posterior wall. For comparison, the right ventriculograms were evaluated on a four-point scale similar to the Sellers classification of mitral regurgitation. The grades by the two methods matched exactly in 36 cases, differed by one level in 23 and by two levels in three. Thus, the two methods showed a good correspondence. Similar results were obtained for the grading based on the area covered by the abnormal signals. We conclude that noninvasive grading of tricuspid regurgitation by ultrasonic pulsed Doppler and two-dimensional echocardiography is practicable.

Adult↗

A novel effect of salmon calcitonin on in vitro Ca-uptake by rat brain hypothalamus: the regional and hormonal specificities.

It was found that salmon calcitonin-I (sCT) inhibited in vitro 45Ca2+-uptake by rat brain hypothalamus blocks in a dose-dependent manner. The minimum effective concentration was estimated to be 10 nM or less. The effect appeared to be specific to the hypothalamus and was not observed with the pons plus medulla oblongata or the cerebral cortex. Two C-terminal fragments of the fish hormone, sCT (10-32) and sCT (22-32), and porcine calcitonin failed to inhibit the ion-uptake though tested in concentrations abolishing 125I-sCT binding to these brain tissues, indicating that the whole structure of sCT is essential for the inhibitory effect but not for the binding. Another finding to be noted was a possible dependency of this effect on the integrity of the cell membrane structure. A crude synaptosomal fraction subsequently prepared from sCT-exposed hypothalamus blocks exhibited a decreased uptake of 45Ca2+, while a corresponding fraction from unexposed tissue did not respond to the hormone. These characteristics of this novel in vitro effect of sCT suggest its possible relevancy to the anorectic effect which also appears to be specific to the fish hormone.

Animals↗

Insulin receptors on erythrocytes and hepatocytes from streptozotocin induced diabetic rats.

Insulin receptors on hepatocytes and erythrocytes were studied in rats two and eight weeks after the injection of streptozotocin (50 mg/kg) to see if erythrocyte insulin receptors change parallel with hepatocyte insulin receptors in response to hypoinsulinemia. Insulin binding to hepatocytes increased two (14.0 +/- 2.5% v.s. 7.7 +/- 0.7%; P less than 0.025) and eight weeks (15.9 +/- 1.9% v.s. 6.6 +/- 1.1%; P less than 0.005) after the streptozotocin injection. Scatchard analysis revealed that this increase was due to a rise in both the receptor concentration and affinity. The number of receptors was comparable in the two- and eight-week-streptozotocin rats while the increase in the affinity was more pronounced in the latter group. Insulin binding to the erythrocytes was also increased in both two- (5.0 +/- 0.7% v.s. 4.2 +/- 0.6%) and eight-week- (4.3 +/- 0.6% v.s. 2.7 +/- 1.2%) streptozotocin rats. This increase was due to a rise in the receptor concentration rather than the affinity. However, compared to hepatocytes, these changes were inconsistent and statistically not significant. Furthermore, no correlation was obtained between the binding and plasma insulin concentration. These results indicate that insulin receptors on rat erythrocytes are less sensitive to a change in the plasma insulin concentration and do not always reflect accurately the receptor state on hepatocytes.

Animals↗

Efficacy of hemoperfusion in the therapy of bromvalerylurea (bromural) intoxication.

We have found that charcoal hemoperfusion is effective in removing bromvalerylurea (BVU) from circulation. A patient poisoned with BVU showed a marked lightening of coma after 3 h of hemoperfusion. The BVU concentration in the patient's serum was decreased significantly by hemoperfusion. In an experiment with dogs without hemoperfusion, the BVU concentration had its peak at the fourth hour after oral administration and decreased in 24 h. In an experiment with hemoperfusion, BVU concentration in dogs decreased markedly during hemoperfusion. After hemoperfusion a rebound of concentration was observed.

Adolescent↗

Studies on new vasodilators, WS-1228 A and B. I. Discovery, taxonomy, isolation and characterization.

New vasodilators, designated WS-1228 A and B have been discovered in the culture filtrate of a strain of Streptomyces aureofaciens. The active compounds were purified by column chromatography with Diaion HP-20 and silica gel, and finally separated from each other by high performance liquid chromatography. They were obtained as pale yellow crystals and their molecular formulae were both C11H17N3O.

Animals↗