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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 937 records · Page 52Linked to original sources

Cerium-based cytochemical method for detection of ouabain-sensitive, potassium-dependent p-nitrophenylphosphatase activity at physiological pH.

We have developed a new cytochemical method for detecting the ouabain-sensitive, potassium-dependent p-nitrophenylphosphatase (K-NPPase) activity of the sodium-potassium-activated adenosine triphosphatase (Na-K ATPase) complex. The incubation medium contains p-nitrophenylphosphate (p-NPP) as substrate, cerium chloride as capture agent, Tricine buffer, MgCl2, and KCl. Tricine buffer protected against the medium turbidity caused by non-enzymatic reaction at pH 7.5. Biochemically, the accumulation of p-nitrophenol and phosphate in the reaction precipitate was proportionally related to the enzyme concentration. Ultracytochemically, the reaction products of the K-NPPase activity were localized as fine and uniform electron-dense deposits in the cytoplasmic side of specialized basolateral plasma membranes of cells of kidney distal convoluted tubules, secretory cells of salt gland, and marginal cells of stria vascularis. This method has the advantage of being useful at physiological pH.

4-Nitrophenylphosphatase↗

[A study of hepato-biliary and alimentary scintigrams using a triple tracer method].

In order to evaluate the gastric emptying and postprandial mixing of bile with food, the scintigraphies of hepatobiliary and gastrointestinal tracts by using three different kinds of radioisotopes were performed simultaneously (99mTc-E.HIDA for hepatobiliary scintigraphy, 111In-DTPA containing orange juice and 131I-albumin containing scrambled egg for gastrointestinal scintigraphy). This method was available for observation of gastric emptying of liquid and solid foods and also examination of the mixing effect of bile and food quantitatively.

Bile↗

[Measurements of monoamine neurotransmitter metabolism by in vivo voltammetry].

In vivo voltammetry is an electrical detection method by which dopamine and serotonin metabolism can be estimated in the brain of animals. In the present report preliminary and basic experiment were performed before its application to ischemic brain. Firstly, using voltammetry DPV-5 system in vitro, concentration/amplitude curve was obtained with various concentration of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) diluted in phosphate buffer (pH 7.4). DOPAC appeared at +150 mV (peak 2) while 5-HIAA appeared at +300 mV (peak 3). A linear relation was obtained in the concentrations ranging 5 x 10(-6)-10(-4) M for DOPAC and 10(-6)-10(-4) M for 5-HIAA. While a delay in oxidation potential was noticed for both peaks 2 and 3 by about 30 mV when the pH of solution was decreased by 1. Secondly the DPV-5 system was applied in vivo to the rat striatum. Peak 2 was observed at +150 mV which was increased by intraperitoneal injection of haloperidol, a dopamine receptor blocker and decreased by pargyline, a monoamine oxidase inhibitor. While peak 3 was observed at +300 mV and increased after probenecid and decreased by pargyline, which suggest that peak 2 and 3 correspond to DOPAC and 5-HIAA respectively. Thirdly DPV-5 system was applied to the rat striatum and rat's heart was arrested by KCl injection as a model of extreme brain ischemia. Shortly after cardiac arrest the heights of peak 2 was significantly increased to 600-900% while the increase of peak 3 was not significant, both of which subsided gradually toward 30 minutes after arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Calmodulin antagonistic action of the cerebral circulation improver 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4- ([4-(2-methoxyphenyl)-1-piperazinyl]methyl)isoquinoline.

6,7-Dimethoxy-1-(3,4-dimethoxybenzyl)-4-([4-(2-methoxyphenyl)-1- piperazinyl]methyl)isoquinoline (Ro 22-4839) is a new cerebral circulation improver with vasospasmolytic properties. Preliminarily, Ro 22-4839-induced arterial relaxation was confirmed under the treatment of various constrictors and it was hardly overcome by addition of extra calcium. In this study the mode and site of action of this agent were further explored. Ro 22-4839 was found to more strongly inhibit the superprecipitation of chicken gizzard smooth muscle actomyosin (IC50 = 2.0 mumol/l) than trifluoperazine (38 mumol/l) and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide) (220 mumol/l), an in vitro model for relaxation-contraction coupling of the smooth muscle in which calmodulin is known to play an important role through phosphorylation of myosin light chain kinase. The calmodulin antagonistic action of Ro 22-4839 was also demonstrated in other calmodulin-related reaction systems such as phosphodiesterase and hydrophobic fluorescent probe, but was very weak in Ca2+, Mg2+-ATPase of rat erythrocyte membrane. Thus, Ro 22-4839 was suggested to have a relative preference for smooth muscle contraction process unlike trifluoperazine and W-7. Moreover, Ro 22-4839 prevented the decrease in erythrocyte deformability induced by hyperosmolarity or intracellular Ca2+ accumulation, like trifluoperazine and W-7. However, Ro 22-4839 itself caused hardly an internal stomatocytic shape of erythrocytes in contrast to known calmodulin antagonists. Further, Ro 22-4839 inhibited erythrocyte membrane rupture, platelet aggregation and lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗

Spasmolytic action of the cerebral circulation improver 6,7-dimethoxy-1- (3,4-dimethoxybenzyl)-4-[( 4-(2-methoxyphenyl)-1-piperazinyl]methyl) isoquinoline in isolated canine vessels.

Vasodilating action of a new calmodulin antagonist, 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4-[( 4-(2- methoxyphenyl)-1-piperazinyl] methyl) isoquinoline (Ro 22-4849) was examined in various isolated canine vessels. Ro 22-4839 was found to dilate basilar and middle cerebral arteries and to non-selectively antagonize submaximal contraction of these arteries under the treatment of various constrictors (K+, Ca2+, PGF2 alpha (dinoprost), serotonin and incubated blood) with IC50 values ranging from 0.043 to 1.69 mumol/l. Vasospasmolytic action of the compound in these cerebral arteries was 9 and 20 times greater than those in coronary and femoral arteries, respectively. The arterial relaxation by Ro 22-4839 was hardly overcome by addition of extra calcium and Ro 22-4839 did not alter calcium channels in the guinea-pig papillary muscle, although the compound inhibited the tension development, confirming its calmodulin antagonistic properties. Ro 22-4839 inhibited norepinephrine (NE)-induced contraction of femoral arterial strips concentration-dependently, and prevented NE-induced lethal extravasation in mice with an ED50 value of 1.96 mg/kg p.o. In in vitro [3H]-dihydroergocryptine binding assay and ex vivo [3H]-WB-4101 (2-[(2',6'-dimethoxy)phenoxyethylamino] methylbenzodioxan) binding assay, the compound showed a potent inhibitory action on alpha 1-adrenoceptor. These findings indicate that Ro 22-4839 exerts the spasmolytic effects on cerebral vessels through calmodulin antagonistic properties combined with alpha 1-adrenoceptor blocking action.

Action Potentials↗

[Longitudinal study of epileptic foci in childhood].

We performed the longitudinal study in patients with focal spikes about characteristic changes in epileptic foci for periods of between one year and 5 years 9 months. The 116 epileptic children were evaluated, ranging in onset age from 10 month to 12 year 9 month old (mean age: 6 year 11 month). They were subdivided into four groups according to their region of foci: group 1, 41 patients with the centro-temporal spikes (Rolandic discharges); group 2, 14 patients with the occipital spikes; group 3, 6 patients with frontal pole spikes; group 4, 55 patients with the other focal spikes. EEG examinations were followed 6 months interval in each patients, and total 412 EEG trancing were investigated. Migration of epileptic foci was recognized in thirty eight patients (32.8%): 17 (41%) in Rolandic discharges, 7 (50%) in occipital spikes, 4 (67%) in frontal pole spikes and 10 (18%) in other spikes. The mean time to the migration of next foci was 45.6 months in Rolandic discharges, 18.4 months in occipital spikes, 17.6 months in frontal pole spike and 61.4 months in other spikes. As to the regions of migrated foci, Rolandic discharges tended to move to the near and horizontal areas such as from central to temporal. Whereas, occipital spikes and frontal pole spikes tended to move to the distant and vertical areas such as from occipital to frontal pole and from frontal pole to occipital. But other spikes showed no tendency.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

[Clinical evaluation of flomoxef in pediatrics and a study on the penetration into cerebrospinal fluid].

The transfer to cerebrospinal fluid of a new oxacephem antibiotic flomoxef (FMOX, 6315-S) and its clinical efficacy against bacterial infections were investigated. 1. In 3 cases of purulent meningitis, cerebrospinal fluid concentrations of FMOX after one shot intravenous injection of 100 mg/kg during the acute stage of infections were 5.12-6.32 micrograms/ml and ratios of FMOX in cerebrospinal fluid in serum were about 5%. During the recovery stage, cerebrospinal fluid concentrations were about 3.8 micrograms/ml and cerebrospinal fluid/serum ratios were about 3.5%. 2. In 1 case of purulent meningitis, the treatment with FMOX was clinically effective but this case was classified as "unevaluable" because other drug was used concomitantly. FMOX was rated effective in other 2 cases of purulent meningitis. Of 9 cases of pneumonia, FMOX was rated very effective in 8 cases and it was rated only effective in the other. Of 4 cases of bronchitis, the drug was rated very effective in 3 cases and only effective in the other. FMOX was rated very effective against 2 cases of tonsillitis, also. 3. As side effects, thrombocytosis was observed in 3 of 20 cases examined. All cases, however, were deemed unrelated to the FMOX treatment and the side effect was only transient as are often found in courses of recovery from infections.

Age Factors↗

[Epithelioid cell-node induced by intracisternal injection of kaolin in rats].

We studied the origin of the epithelioid cells (macrophages) observed in the rat brain in response to the intracisternal injection of kaolin. The rats, two days of age, were used. The animals were killed after thirteen weeks following cisternal injection of kaolin. Massive epithelioid cell-nodes with multifocal necrosis were seen in the subarachnoid space of the cerebellum, in the cerebellar parenchyma and in the fourth ventricle. They were also present in the choroid plexus. The papillary epithelioid cell-nodes were observed onto the aqueduct of Sylvius, the third and lateral ventricles. These were associated with the proliferation of the adventitia of the blood vessel in the subependymal white matter. This suggested that the vascular adventitia played a role for a formation of the epithelioid cell-node in this case. The epithelioid cell was negative in silver-stained preparation. This indicated that microglia was not a source of the epithelioid cell. Reticulin fibers were moderately increased in the lesions. The epithelioid cells phagocytized kaolin granules and gave a strong PAS-positive reaction. However, it seemed that the PAS-positive materials were not identical to the kaolin granules. A rich accumulation of apparently extra- and intracellular kaolin deposits stained metachromatically violet with toluidine blue was seen in the necrotic areas. A large number of the degenerated cells containing kaolin deposits was found especially in the marginal zone of the necrotic areas. Granulation tissue with the amount of spindle-form cells and collagen fibers was also observed in the subarachnoid space. The granulation tissue was formed by hyperplasia of fibroblasts following the proliferation of the epithelioid cells and their necrotic processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗