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Biomedical subjects

S Kudo

Publications and source records attributed to S Kudo.

At least 307 records · Page 17Linked to original sources

Different effects of various beta-adrenoceptor antagonists on adenylate cyclase, guanylate cyclase and calmodulin-dependent phosphodiesterase in heart.

A series of six beta-adrenergic blocking drugs including propranolol, bufetolol, bunitrolol, pindolol, labetalol and acebutolol were examined for effects on adenylate cyclase, guanylate cyclase and calmodulin-dependent phosphodiesterase from heart. The adrenergic blocking agents had no apparent effects on basal activities of adenylate cyclase, guanylate cyclase and phosphodiesterase. The drugs blocked the enhancement of adenylate cyclase activity by isoproterenol, but not by guanine nucleotide or fluoride. The inhibitory effects of beta-antagonists were overcome by sufficiently large doses of isoproterenol. Sodium azide specifically required catalase whereas NaNO2 required cysteine to activate myocardial guanylate cyclase. Among beta-adrenergic blocking drugs tested, both pindolol and acebutolol inhibited the stimulation of guanylate cyclase by NaNo2 or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). However, other beta-blocking drugs did not significantly affect the activation by NaN3, NaNO2 and MNNG. Several beta-antagonists, such as labetalol, bunitrolol, pindolol and acebutolol were also effective in blocking the activation of phosphodiesterase by calmodulin. The inhibitory effects of beta-adrenergic blocking drugs, i.e. pindolol and acebutolol upon either nitroso compound-stimulated guanylate cyclase or calmodulin-activated phosphodiesterase display little correlation with their potency as beta-adrenergic blocking agents. These data suggest that beta-antagonists may have another site of action which is not directly related to the control of catecholamine metabolism.

Adenylyl Cyclases↗

Transcatheter thrombolysis in cancer patients.

Arterial thrombolysis was successfully accomplished in 15 of 18 (83%) cancer patients by the continuous intraarterial transcatheter administration of streptokinase (70 units/kg/h or 5000 u/h and/or urokinase (400-500 u/kg/h) over 24-96 h. In 16 of these patients, the arterial thrombosis was a complication of transcatheter infusion of chemotherapeutic agents or embolization therapy. A combination of streptokinase, urokinase and heparin (10,000-25,000 U/day) was utilized without significant side effect and was effective in all 8 patients receiving treatment. Creating a tunnel through the clot, daily monitoring of the catheter with repositioning when necessary, and adjusting the type and dose of thrombolytic agent aided the therapeutic management.

Adolescent↗

Interaction of calcium-binding proteins with calmodulin-dependent guanylate cyclase in Tetrahymena plasma membrane.

Addition of bovine brain calmodulin and S-100 inhibited Tetrahymena calmodulin-induced stimulation of guanylate cyclase, but they did not affect enzymatic activity in the presence of calcium alone. Troponin C shows little effect on the cyclase activity regardless of the presence or absence of Tetrahymena calmodulin. The inhibitory effects of brain calmodulin and S-100 were overcome by the addition of Tetrahymena calmodulin, but not by calcium. Both calmodulins from Tetrahymena and bovine brain elicited stimulation of heart phosphodiesterase, while troponin C and S-100 did not affect the phosphodiesterase activity in the presence and absence of Tetrahymena calmodulin.

Animals↗

Regulation by calcium of hormone-insensitive adenylate cyclase and calmodulin-dependent guanylate cyclase in Tetrahymena plasma membrane.

Agents such as 5'-guanylyl-imidodiphosphate(GppNHp), fluoride and forskolin did not activate adenylate cyclase from Tetrahymena. In addition, the cyclase was not stimulated by hormones including catecholamines and glucagon when assayed with or without GppNHp at conditions where they increased adenylate cyclase activity from rat heart. Sodium azide, NaNO2 or N-methyl-N'-nitro-N-nitroguanidine (MNNG) failed to activate Tetrahymena guanylate cyclase. Adenylate cyclase activity was activated at low free Ca2+ level and inhibited at high levels, while guanylate cyclase activity was activated by Tetrahymena calmodulin only at high physiological concn of Ca2+.

Adenylyl Cyclases↗

Growth-dependent changes of guanylate and adenylate cyclase activities in cilia and cell bodies of Tetrahymena pyriformis.

The calmodulin-dependent guanylate cyclase of Tetrahymena pyriformis was shown previously to be localized in surface membranes (ciliary and pellicular membranes) (Kudo, S, Nakazawa, K, Nagao, S & Nozawa, Y, Japan j exp med 52 (1952) 193) [21], whereas in a recent report Schultz et al, (Schultz, J E, Schonefeld, U & Klumpp, S, Eur j biochem 137 (1983) 89) [12] demonstrated the localization of this enzyme in ciliary membrane, arguing against its presence in pellicular membrane. To examine the discrepancy, the activities of guanylate and adenylate cyclases were examined in cilia and cell bodies of Tetrahymena pyriformis during transition from early log to stationary growth phase. The guanylate cyclase activity in the cell bodies increased significantly with growth of age, while in cilia the activity was rather consistent. In contrast, adenylate cyclase did not show any growth-dependent activity changes in both cilia and cell bodies. The increase of guanylate cyclase activity was not related to the increase of its activator calmodulin, because the change in enzyme activity could not be negated by addition of a saturating amount of calmodulin. These results suggest that the content of guanylate cyclase itself would be increased in the cell bodies during growth.

Adenylyl Cyclases↗

Moya moya disease: use of digital subtraction angiography in its diagnosis.

Fourteen patients suspected of having Moya Moya disease underwent intravenous digital subtraction angiography (DSA), and the findings from nine of these patients were reviewed and analyzed. Obstruction or stenosis of the supraclinoid portion of the internal carotid artery and the proximal portions of the anterior and middle cerebral arteries was observed in all cases. Arteriography, however, was better than intravenous DSA in demonstrating Moya Moya vessels, differentiating complete occlusion from severe stenosis, and demonstrating important transdural collaterals. The disadvantages of intravenous DSA included inferior spatial resolution, the need for large amounts of contrast media, and relatively high radiation doses. Since the summation of vessels cannot be avoided using DSA, arteriography is necessary for the precise evaluation of cerebral hemodynamics before bypass surgery. Intravenous DSA is a safe, reliable method for diagnosing Moya Moya disease and is suitable for the screening and follow-up examinations of patients with the disease.

Adolescent↗

The absorption, distribution and excretion of a new antithrombotic and vasodilating agent, cilostazol, in rat, rabbit, dog and man.

The absorption, distribution and excretion of a new antithrombotic and vasodilating agent, cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)- qui nolinone, OPC-13013) was studied after the oral administration of cilostazol or 14C-cilostazol in rats, rabbits, dogs and man. After the oral administration of 14C-cilostazol at a dose of 10 mg/kg in male and female rats and rabbits, and at a dose of 3 mg/kg in dogs, the Tmax, Cmax and T1/2 of the radioactivity were 2 h, 710.5 ng eq X ml-1 and 2.5 h in male rats, 4 h, 11 002.8 ng eq X ml-1 and 3.7 h in female rats, 8 h, 358.1 ng eq X ml-1 and 6.9 h in rabbits, and 3 h, 559.4 ng eq X ml-1 and 1.6 h in dogs, respectively. After the oral administration of 14C-cilostazol at a dose of 10 mg/kg in rats, tissue concentrations of radioactivity in female rats were about 3 to 5 times as high as those in male rats. The blood and tissue concentrations of radioactivity in male and female rats showed a marked sex difference. However, the concentrations in the blood in both male and female rats declined rapidly. There was no evidence of the accumulation of radioactivity in the tissues due to repeated oral administrations of 14C-cilostazol at a dose of 3 mg/kg once a day for 21 days in male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

The metabolism of a new antithrombotic and vasodilating agent, cilostazol, in rat, dog and man.

The metabolism of cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)- qui nolinone, OPC-13013) was studied after the oral administration of cilostazol or 14C-cilostazol in rats, dogs and man. Metabolites of cilostazol identified in the rat, dog and human plasma and urine were monohydroxycilostazol (OPC-13213, OPC-13217, OPC-13366, OPC-13371, OPC-13215 and OPC-13326), monohydroxydehydrocilostazol (OPC-13269 and OPC-13388), 3,4-dihydro-6-hydroxy-2(1H)-quinolinone (6-HQ), their conjugates and dehydrocilostazol (OPC-13015). Major metabolites detected in the rat plasma were OPC-13015, OPC-13217 and OPC-13213, and the plasma concentration of OPC-13015 was 53 to 79% of that of cilostazol. In the dog plasma, major metabolites detected were OPC-13213, OPC-13366 and OPC-13015, and the AUC of OPC-13213 was 79.7% of that of cilostazol. In the human plasma, major metabolites detected were OPC-13015 and OPC-13213, and their AUC were 11.7 and 9.1% of that of cilostazol, respectively. Monohydroxycilostazol and monohydroxydehydrocilostazol were detected at 8.5% of dose in the rat urine and 8.7% in the dog urine, and OPC-13213 showed the highest concentration of these. The conjugates of these and 6-HQ were detected at 0.4 and 24.5%, respectively, in the rat urine and 2.4 and 3.7%, respectively, in the dog urine. These conjugates were mainly sulfate in rats and glucuronide in dogs. In the human urine, OPC-13213 showed the highest concentration, and the conjugates were mainly glucuronide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Case report of translumbar renal angiography and embolization.

The translumbar approach was used for renal angiography and transcatheter embolization in a patient whose usual sites of vascular entry were not available because of arteriosclerotic occlusive vascular disease. A description is given of the reasons for embolization and the method used.

Aged↗

Posttranscatheter embolization computed tomography in hepatocellular carcinoma. Evaluation of embolization effects.

The postcontrast CT scans and angiography of 26 lesions in 23 patients with hepatomas who underwent transcatheter arterial embolization therapy were reviewed. Newly developed low density and high density areas and gas were noted on CT scans of the tumors after embolization in 100, 8 and 58% of the lesions, respectively. The CT findings of residual tumors correlated well with those of follow-up angiography. When discrete smooth round low density zones were observed on CT, there was no residual neovascularity on follow-up arteriography. When there were nodular or thick septum-like structures in low density lesions, arteriography revealed residual tumor vascularity in the lesions. CT proved useful not only in evaluating the effects of embolization, but also in providing important information about residual tumors.

Aged↗