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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 469 records · Page 26Linked to original sources
PubMed1993

Effects of microinjection of a GABA antagonist into the periaqueductal gray upon electrically-induced vocalization in decerebrate cats.

The effects of the GABA antagonist bicuculline methiodide (BIC), microinjected into the ventrolateral periaqueductal gray (PAG) on the stimulus threshold of electrically-induced vocalization were examined in unanesthetized precollicular-postmamillary decerebrate cats. To induce vocalization, repetitive electrical stimulation (0.2 ms, 100 Hz, 5-10 s duration) was delivered to the caudal portion of the PAG (30 to 300 microA) or the pontine call site (PCS) (10 to 60 microA) in the ventrolateral pontine reticular formation. Injection of 0.1 microliter of 2 mM BIC into the caudal portion of the PAG decreased the stimulus thresholds of the PCS and the injection site for about 1 h. Injection of BIC into the reticular formation near the PAG, where the electrical stimulation induced vocalization, did not decrease the stimulus thresholds of the PCS or the injection site. These results indicate that GABAergic inhibition regulates the excitability of the cells within the ventrolateral PAG, which exerts an excitatory effect on the lower brain structures that produce vocalization.

Animals↗
PubMed1993

Metabolic interaction of ethanol and cyclohexanone in rabbits.

The interaction of ethanol (EtOH) and cyclohexanone (CHN) metabolism was studied to demonstrate the influence of alcohol beverage in cyclohexanone poisoning. Rabbits were administered CHN and EtOH separately or together, and the plasma concentration of CHN and cyclohexanol (CHL), a metabolite of CHN, and blood concentrations of EtOH were measured at various times. When CHN alone was administered orally, the time to maximum plasma concentration (Tmax) of CHN was as short as 15 min, but that of CHL was 120 min. The short Tmax of CHN was considered to be due to the first-pass effect. The plasma concentration of CHL was much greater than that of CHN. On the other hand, when the same amount of molar CHL was administered in rabbits for sake of comparison, only small amounts of CHN were detected in plasma. The interconversion between CHN and CHL at the time of equilibration tended to shift predominantly toward the formation of CHL, whose plasma concentration ratio was about 1:6 to 1:8. The coadministration of EtOH decreased the plasma concentration of CHN and increased that of CHL more than the administration of CHN alone. The blood concentration of EtOH was also decreased with the coadministration of CHN. The coadministration of EtOH with CHN demonstrated an acceleration in the metabolism of both CHN and EtOH, which may be due to an increase in the concentrations of the alcohol dehydrogenase-NADH and -NAD complexes.

Administration, Oral↗
PubMed1993

Evaluation of oral anticoagulant therapy by measuring plasma prothrombin fragment 1 + 2.

To assess the degree of haemostatic system activation, plasma levels of prothrombin fragment 1 + 2 (F1 + 2), a direct indicator for thrombin generation in vivo, were measured in 49 patients with thrombotic disease undergoing long-term warfarin therapy (Thrombotest values < or = 40%). In these patients, vitamin K dependent coagulation factors (factors II, VII, IX and X) were decreased together with the anticoagulant proteins C and S, but the mean plasma concentration of F1 + 2 was significantly decreased compared with 48 healthy subjects. In warfarin-treated patients, F1 + 2 was positively correlated with the Thrombotest value, factors II, VII, IX and X. When analysed according to the intensity of anticoagulation, patients with Thrombotest values less than 30% showed a significant decrease in F1 + 2, but the mean F1 + 2 level was normal in patients with Thrombotests higher than 30%. These findings indicate that long-term oral anticoagulant therapy suppresses thrombin generation approximately in parallel to the decrease in coagulation factors, and levels of F1 + 2 lower than healthy subjects are observed when Thrombotest values are less than 30%.

Administration, Oral↗
PubMed1993

Prevalence of volatile solvent inhalation among junior high school students in Japan and background life style of users.

In order to estimate the prevalence of volatile solvent inhalation among junior high school students in Japan and to assess certain characteristics of the lifestyle of these users, the authors surveyed 5240 students 12-15 years of age. This was the first major survey of the prevalence of volatile solvent inhalation among junior high school students in Japan, from the point of view of the number of subjects and schools. 1.5% of subjects were students who had inhaled solvents. The regularity of life style rhythm was more significantly disturbed in Lifetime Users than in Non-Users. School life and family life were significantly less relaxed for Lifetime Users than for Non-Users. Drinking alcohol and smoking had a strong relationship with inhaling volatile solvents. The authors suggest that greatly increasing education on the harmful effects of volatile solvents inhalation and increasing the frequency with which the entire family eats dinner together will be an effective prevention strategy in Japan.

Adolescent↗
PubMed1993

Clinical experience using the Bio-pump for extracorporeal circulation during open-heart surgery.

The Bio-pump is still being used in a wide range of clinical applications such as open-heart surgery, left-heart bypass, extracorporeal membrane oxygenation, and supplementary circulation. Clinical application of the Bio-pump for extracorporeal circulation in 21 patients undergoing open-heart surgery was compared with application of the roller pump in terms of their effects on hemolysis, platelet function, and renal function. Although the amount of hemolysis was not significantly different between the Bio-pump group and the roller-pump group, platelet function was slightly better maintained in the Bio-pump group as judged by the levels of platelet factor 4, beta-thromboglobulin, and 6-keto-prostaglandin F1 alpha/thromboxane B2. There was no difference between the two pumps in terms of their effects on renal function. The above findings lead us to conclude that there is a slight advantage to use of the Bio-pump in clinical settings.

Blood Platelets↗
PubMed1993

[An infection model which was induced in a carboxymethyl cellulose (CMC) pouch on the back of the rat].

The air-pouch model of inflammation in rats is excellent in that it allows quantitative evaluation of inflammation, and it is used for analysis of inflammatory mediators and as an evaluation system for anti-inflammatory drugs. We investigated the possibility of using this system as an experimental infection system. As a result, inflammation was found to be caused by injection of a constant amount of Staphylococcus aureus solution (10(4)-10(8)). The amount of infiltration and the number of infiltrating cells varied with quantity of bacteria. The infiltrating cells consisted mainly of neutrophils. In this experimental model of infectious disease, the severity of inflammation could be quantitatively evaluated as a function of time in terms of bacterial proliferation and the body's response to bacterial proliferation based on the amount of fluid in the air pouch and the number of infiltrating cells, suggesting that the model is useful. In this experimental system, there were no differences between the number of live bacteria, the number of infiltrating cells or the amount of infiltration when S. aureus Smith strain and clinically-isolated methicillin-resistant S. aureus (MRSA) were used, suggesting that there is no difference between the inflammation-induced activity of MRSA and MSSA.

Animals↗
PubMed1993

Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin.

In a previous study (H. Shirataki, K. Kaibuchi, T. Yamaguchi, K. Wada, H. Horiuchi, and Y. Takai, J. Biol. Chem. 267:10946-10949, 1992), we highly purified from bovine brain crude membranes the putative target protein for smg p25A/rab3A p25, a ras p21-related small GTP-binding protein implicated in neurotransmitter release. In this study, we have isolated and sequenced the cDNA of this protein from a bovine brain cDNA library. The cDNA had an open reading frame encoding a protein of 704 amino acids with a calculated M(r) of 77,976. We tentatively refer to this protein as rabphilin-3A. Structural analysis of rabphilin-3A revealed the existence of two copies of an internal repeat that were homologous to the C2 domain of protein kinase C as described for synaptotagmin, which is known to be localized in the membrane of the synaptic vesicle and to bind to membrane phospholipid in a Ca(2+)-dependent manner. The isolated cDNA was expressed in COS7 cells, and the encoded protein was recognized with an anti-rabphilin-3A polyclonal antibody and was identical in size with rabphilin-3A purified from bovine brain by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Moreover, both rabphilin-3A purified from bovine brain and recombinant rabphilin-3A made a complex with the GTP gamma S-bound form of rab3A p25 but not with the GDP-bound form of rab3A p25. Immunoblot and Northern (RNA) blot analyses showed that rabphilin-3A was highly expressed in bovine and rat brains. These results indicate that rabphilin-3A is a novel protein that has C2 domains and selectively interacts with the GTP-bound form of rab3A p25.

Adaptor Proteins, Signal Transducing↗
PubMed1993

Evaluation of the combination of a tissue-type plasminogen activator, SUN9216, and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model.

BACKGROUND AND PURPOSE: We aimed to evaluate a modified tissue-type plasminogen activator, SUN9216, and the combination of SUN9216 and a thromboxane A2 receptor antagonist, vapiprost, in a rat middle cerebral artery thrombosis model. METHODS: Under anesthesia, the left middle cerebral artery was observed under an operation microscope without cutting the dura mater via a subtemporal craniotomy. Photoillumination (wave length, 540 nm) was applied to the middle cerebral artery, and then rose bengal (20 mg/kg) was administered intravenously. The reopening of the middle cerebral artery by SUN9216, injected 30 minutes after middle cerebral artery occlusion, was observed under an operation microscope for a 60-minute observation period. Twenty-four hours after the operation, sections of the cerebrum were stained with triphenyltetrazolium chloride, and the area of cerebral infarction was analyzed by a computer. RESULTS: The combination of SUN9216 and vapiprost caused reopening of the middle cerebral artery in 58.8% of the rats, which was a greater percentage than that achieved with SUN9216 alone (31.6%). In contrast, saline did not cause reopening of the middle cerebral artery during the 60-minute observation period. The area of cerebral infarction in rats reperfused with SUN9216 was significantly reduced compared with that in the control group. The infarction area in rats treated with the combination of SUN9216 and vapiprost was reduced compared with that in rats treated with SUN9216 alone; this was the case whether or not the occlusion was reperfused. There was a significant correlation between the time of reopening of the middle cerebral artery and area of cerebral infarction. CONCLUSIONS: A single injection of SUN9216 was effective in recanalizing the vessel and reducing the area of cerebral infarction.

Animals↗
PubMed1993

Intraventricular administration of histidyl-proline-diketopiperazine [Cyclo(His-Pro)] suppresses prolactin secretion and synthesis: a possible role of Cyclo(His-Pro) as dopamine uptake blocker in rat hypothalamus.

Histidyl-proline-diketopiperazine [Cyclo (His-Pro) (CHP)] was discovered to be one of the metabolites of TRH. To understand the specific role of CHP in rat hypothalamic dopamine neurons, we examined the in vivo effects of intraventricular (icv) infusion of CHP on the release and synthesis of PRL in the rat pituitary and the 3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine ratio in the rat hypothalamus. We also examined the in vitro effects of CHP on the release of [3H]dopamine from dispersed tuberoinfundibular dopamine neurons, [3H]dopamine reuptake in hypothalamic membrane fractions, and PRL release from rat pituitary cultured cells. Female rats were treated by icv infusion of 1 microM CHP daily for 1, 3, and 7 days, using Alzet osmotic pumps. After 1 day of treatment, the serum PRL concentration was significantly decreased. Northern blot analysis of the total RNA isolated from the pituitary glands of control animals using 32P-labeled PRL cDNA as a probe indicated the presence of PRL gene transcript, 1.0 kilobase in size, and its amount was decreased by CHP treatment. CHP did not affect [3H]dopamine release from dispersed tuberoinfundibular dopaminergic neurons at any concentration up to 1 microM. CHP did not inhibit PRL release from cultured pituitary cells at low concentrations (1-100 nM), but it stimulated PRL release at high concentrations (1 and 10 microM). We also examined the concentrations of dopamine and DOPAC in the rat hypothalamus when CHP was administered icv for 1 or 7 days. There was a significant decrease in the DOPAC/dopamine ratio after CHP treatment for 1 day. Furthermore, CHP caused dose-dependent inhibition of [3H]dopamine uptake by the rat hypothalamus similar to other dopamine uptake blockers, such as benztropine and GBR12909. These data suggest that icv administration of CHP might decrease both PRL secretion and accumulation of PRL gene transcripts in the pituitary by decreasing the DOPAC/dopamine ratio and inhibiting dopamine reuptake in the rat hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Mitochondria-selective reduction of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain; a novel radiopharmaceutical for brain positron emission tomography (PET) imaging.

The retention mechanism of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) in the murine brain was evaluated. For this purpose, stable Cu-PTSM was subjected to electron spin resonance spectrometry (ESR) and high performance liquid chromatography (HPLC) analysis to determine the valence state, coordination structure and tissue metabolism. In murine brain homogenate, ESR and HPLC analysis indicated the reduction and cleavage of Cu(II)-PTSM to Cu(I). This virtually irreversible reduction was specifically initiated by the mitochondrial enzymatic system in the murine brain.

Animals↗
PubMed1993

Isolation of bilobalide and ginkgolide A from Ginkgo biloba L. shorten the sleeping time induced in mice by anesthetics.

The leaves of Ginkgo biloba L. and aqueous extract from them shortened the sleeping time induced in mice by anesthetics (hexobarbital, alpha-chloralose and urethane, i.p.). Two characteristic terpenoids in G. biloba, bilobalide and ginkgolide A, significantly shortened the sleeping time induced by anesthetics. A toxic substance, 4-O-methylpyridoxine (MPN), responsible for "gin-nan food poisoning" isolated from the seed of G. biloba, was not detected from the extract of the leaves of G. biloba. Therefore, the Ginkgo biloba extract has no toxicities for MPN.

Anesthetics↗
PubMed1993

[Studies on the constituents of edible and medicinal plants. IV. Determination of 4-O-methylpyridoxine in serum of the patient with gin-nan food poisoning].

The serum 4-O-methylpyridoxine (MPN) levels in a 21 months-old patient with gin-nan food poisoning were determined by HPLC. The blood of the patient was taken at 8.5 and 15.5 h after taking about 50 ginkgo albumens. After deproteinization of the serum, the supernatant was pretreated with Sep-pak C18 cartridge and was applied to HPLC. HPLC was performed with a Hibar LiChrosorb RP-18 (4.0 mm i.d. x 250 mm, 7 microns) using a fluorescence detector (wave length of excitation and fluorescence; 290 and 400 nm, respectively). The serum MPN level was determined by the absolute calibration method. The determination limit of MPN in the serum was 0.05 micrograms/ml. The serum MPN concentration was 0.09 micrograms/ml at 8.5 h after taking ginkgo seeds, and was less than the determination limit of MPN (0.05 micrograms/ml) at 15.5 h. MPN, isolated from the seed of Ginkgo biloba L., is responsible for "gin-nan food poisoning," and its cardinal symptoms are mainly tonic and/or clonic convulsions and loss of consciousness. Infants are particularly vulnerable. This method may be available for proving the gin-nan food poisoning, chemically.

Chromatography, High Pressure Liquid↗
PubMed1993

An outbreak of Salmonella typhimurium infection in bengalees, a variety of Lonchura striata.

Bengalees (a variety of Lonchura striata) in an aviary in Nagano Prefecture died of severe diarrhea in 1991. Pathological examination revealed slight enlargement of the liver and spleen. Histopathologically, necrotic granulomatous lesions were seen in the liver. Salmonella Typhimurium was isolated from the main organs and fecal samples. No evidence of Newcastle disease or chlamydiosis was detected. The disease was finally diagnosed as S. Typhimurium infection in bengalees. In spite of some countermeasures, 198 out of 268 birds died within 6 months, a mortality rate of 74%. Epizootiological survey revealed that the infection was transmitted by birds introduced from another prefecture. This is the first report of S. Typhimurium infection in bengalees.

Animals↗
PubMed1993

Effect of sustained hyperglycemia on the release of insulin from the isolated perfused rat pancreas.

The modulation of insulin release from the isolated pancreas using normal rats rendered hyperglycemic by in vivo glucose infusion was studied. In 24 h and 48 h hyperglycemic rats, the increase in the amount of insulin released was reduced in response to glucose challenge, but was unchanged in relation to arginine challenge. In 48 h hyperglycemic rats insulin secretion after glucagon challenge was preserved. It was concluded that hyperglycemia itself makes the pancreatic B-cell selectively insensitive to glucose.

Animals↗
PubMed1993

Hemodynamic effects on thrombogenesis and platelet aggregation in spontaneously hypertensive rats.

The present study was conducted to investigate the effect of hypertension on the formation of arterial thrombus in the rat femoral artery. The time required to establish the thrombus following endothelial injury in spontaneously hypertensive rats (SHR) was extremely prolonged. Pretreatment with prazosin which lowered the blood pressure near the level in normotensive Wistar Kyoto (WKY) rats, significantly shortened the thrombogenesis time, but it was still longer than that in WKY rats. Platelet aggregation in response to collagen with washed platelets and whole blood was reduced in SHR with and without hypotensive treatment, in comparison with that in WKY rats. Prazosin did not affect the platelet aggregability. Therefore, the decreased platelet aggregation was considered to be responsible for the delayed thrombus formation in hypotensively treated SHR. These results suggested that high blood pressure, mainly, interferes with the establishment of thrombus directly. Hypoaggregability of platelets is likely to be partly involved in the prolongation of thrombogenesis in SHR.

Animals↗
PubMed1993

Significance of glomerular deposition of plasmin-alpha 2-plasmin inhibitor complexes in various glomerulopathies.

To elucidate the relationship between glomerular deposition of plasmin-alpha 2-plasmin inhibitor complexes (PIC) and renal lesions or dysfunction, 25 patients with various glomerulopathies and various degrees of renal injuries were examined. Glomerular PIC deposition was found in eight patients (group A), and other 17 patients showed no deposition (group B). PIC was found mainly in the mesangium and along the capillary loops. Group A showed significantly more severe hematuria (p < 0.05) than group B. Group A showed a significant decrease in glomerular filtration rate (GFR; p < 0.05): the mean values being 60.8 +/- 39 in group A and 94.5 +/- 32 ml/min in group B. Group A showed a significant decrease in the phenolsulfonphthalein excretion test (p < 0.05). There was no significant difference in the mean values of plasma PIC, D-dimer, and thrombin-antithrombin III complexes (TAT) between two groups. Histologically, group A showed a significantly high incidence of adhesion (p < 0.05), crescentic formation (p < 0.05), endothelial swelling and/or detachment (p < 0.01), tubulointerstitial changes (p < 0.01), and glomerular deposition of platelet factor 4 (p < 0.01). The present study demonstrates that glomerular PIC deposition reflects the existence of activation of coagulation and fibrinolysis within the glomeruli and suggests that glomerular PIC deposition plays a part in the progression of renal injuries in various glomerulopathies.

Antifibrinolytic Agents↗
PubMed1993

Oxygen radical scavengers and renal protection by indapamide diuretic in salt-induced hypertension of Dahl strain rats.

In addition to the hemodynamic components, the roles of various humoral factors have been emphasized in the progression of vascular and renal injury in hypertension. Radical scavenging properties have attracted much attention in this field. This article discusses the implication of antioxidant properties of the antihypertensive diuretic indapamide on renal injury in Dahl salt-sensitive (Dahl S) rats. Hydroxyl radicals, oxygen radicals toxic to cellular membranes, are eradicated by indapamide in different assay systems, e.g., reduction of alpha-alpha-diphenyl-beta-picrylhydrazyl, rat brain homogenate, or xanthine-xanthine oxidase systems. Such antioxidant effects of indapamide are primarily due to inhibition of lipid peroxidation induced by hydroxyl radicals, and this mechanism may stimulate prostacyclin generation through activation of prostacyclin synthase. In fact, the antioxidant properties of indapamide are well expressed in vivo as well; indapamide treatment reduced oxygen radicals in the kidney of Dahl S rats with hypertension. This was accompanied by a functional improvement of the kidney; decreases in urinary protein and n-acetylglucosaminidase excretion and an increase in glomerular filtration rate were observed. In addition, indapamide morphologically ameliorated the renal injury, and decreased glomerular sclerosis score, arterial injury, and renal tubular injury. Trichloromethiazide reduces blood pressure similar to that produced by indapamide. However, trichloromethiazide did not lead to reduction of oxygen radicals in the kidney, and did not improve the functional disturbance or morphological injury seen in Dahl S rats. These results indicate that indapamide has antioxidant properties, and in addition to blood pressure reduction, such radical scavenging effects may contribute to its beneficial effects on renal function in vivo.

Animals↗