Search PubMed⌕ Search

Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 523 records · Page 29Linked to original sources
PubMed1990

Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node.

1. Effects of okadaic acid on electrical responses and spontaneous activity in the dominant pacemaker cells of rabbit sinus node were investigated by use of microelectrode techniques. 2. Okadaic acid (10(-5) M to 4 x 10(-5) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by increases in both maximum upstroke velocity at phase 0 (Vmax) and amplitude of action potential. 3. All of the effects of okadaic acid were relatively well preserved in a low-Ca2+ medium (0.12 mM). Okadaic acid restored the spontaneous activity of sinus node pacemaker cells even in a Ca2(+)-deficient medium. 4. The effects of okadaic acid were markedly inhibited or abolished in a low Na+ medium (24 mM or 70 mM) and in the presence of a slow channel blocking agent, verapamil (10(-6) M). 5. In voltage-clamp experiments using a two-microelectrode technique, okadaic acid (10(-5) M) caused an increase in the slow inward current without affecting the outward current. At a higher concentration (4 x 10(-5) M), the drug increased the outward current. 6. These results indicate that okadaic acid causes an increase in spontaneous activity of sinus node pacemaker cells mediated by an enhancement of slow inward current (Isi) through verapamil-sensitive Ca2+ channels.

Action Potentials↗
PubMed1990

Negative inotropic effects of disopyramide on guinea-pig papillary muscles.

1. The inhibitory effects of disopyramide on electromechanical responses were investigated in guinea-pig papillary muscles driven by electrical stimuli. Disopyramide up to 10(-5) M did not cause a negative inotropic effect, while the maximum upstroke velocity of the action potential (dV/dtmax) was significantly decreased. 2. At higher concentrations, this drug dose-dependently inhibited the contraction, and dV/dtmax was further decreased. This inhibition of contraction was accompanied by a depression of the slow action potential in partially depolarized preparations by increasing [K+]0 (26 mM). 3. In preparations pretreated with nifedipine (10(-6) M) and ryanodine (10(-6) M), the contraction was almost completely inhibited. In such preparations, ouabain (2 x 10(-6) M) markedly increased the contraction, probably through the Na(+)-Ca2+ exchange mechanism. This contraction was inhibited by disopyramide above 10(-8) M, and an almost complete inhibition was caused at 3 x 10(-5) M. 4. A similar inhibitory effect was observed on the contraction increased by the lowering of [Na+]0 (36 mM). 5. These results suggest that disopyramide at high concentrations inhibits Ca influx through slow Ca2+ channels and at low concentrations, it reduces the contraction increased through the Na(+)-Ca2+ exchange mechanism. Disopyramide had a greater effect on cardiac contractility mediated by the Na(+)-Ca2+ exchange mechanism.

Action Potentials↗
PubMed1990

Glycyrrhetinic acid derivatives: anti-nociceptive activity of deoxoglycyrrhetol dihemiphthalate and the related compounds.

The possible inhibitory effect of deoxoglycyrrhetol dihemiphthalate (I) and the related compounds (18 beta-olean-9(11),12-diene-3 beta,30-diol) (II) and (olean-11,13(18)-diene-3 beta, 30-diol) III derived from glycyrrhetinic acid has been examined on acetic acid-induced writhing in mice. The compounds inhibited writhing dose-dependently. Their ED50 values were 14, 31 and 22 mg kg-1 for I, II, and III, respectively. The compounds like aspirin, also significantly suppressed PGE2 production in peritoneal fluid together with the writhing response. The results suggests that the analgesic effect of deoxyglycyrrhetol dihemiphthalate and the related compounds is partially due to inhibition of PGE2 production.

Analgesics↗
PubMed1990

Nephritogenic glycoprotein. XIV. A simple isolation method of nephritogenoside.

Normal rat renal cortex contains three renal disease-inducing substances, that is, nephritogenoside, FX1A and immunogenoside (a novel renal glycoprotein that has the biological activity to induce only active Heymann nephritis). When renal cortex homogenate was treated with a detergent, Triton X-100, nephritogenoside was not eluted in the supernatant in which massive doses of FX1A and immunogenoside were detected. Thus, we searched for nephritogenoside in the precipitate. The precipitate was solubilized with trypsin, and nephritogenoside was easily and effectively isolated through columns of DEAE-cellulose followed by Bio-Gel A-1.5 m. The purified sample thus obtained is only composed of nephritogenoside, and contains neither FX1A nor immunogenoside. The yield of purified nephritogenoside was 3.8 mg (starting from 150 rats), which is about 5-6 times the recovery of the previous methodology. This newly developed simple method may be useful for the isolation of purified nephritogenoside. The chemical and immunologic properties of the purified sample prepared by the new method corresponded well with those of the nephritogenoside which was obtained by the previous methodology after exhaustive digestions with three proteolytic enzymes from homologous renal cortex.

Amino Acid Sequence↗
PubMed1990

Therapeutic treatment of New Zealand mouse disease by a limited number of anti-idiotypic antibodies conjugated with neocarzinostatin.

-81 and NE-1 idiotypes (Id) of human nephritogenic anti-DNA antibodies are interspecies Id expressed also in NZB/W F1 mice. We tried to manipulate the synthesis of spontaneously occurring anti-DNA antibody using monoclonal anti-Id antibodies (D1E2 and 1F5) conjugated with a cytotoxic agent, neocarzinostatin (NCS). In vivo administration of anti-Id antibodies conjugated with NCS brought about an improvement in the survival rate of female NZB/W F1 mice. It also caused a retardation of development of lupus nephritis and decreased the numbers of anti-DNA-producing cells. The suppression of anti-DNA antibody synthesis was specific and Id-mediated. The results indicate that the use of a limited number of anti-Id antibodies in combination with a cytotoxic agent may be applicable therapeutically to autoimmune diseases.

Animals↗
PubMed1990

Cardiac rupture following acute myocardial infarction in systemic lupus erythematosus: case report.

A thirty-three year-old woman with systemic lupus erythematosus (SLE) suffered from acute myocardial infarction. Prednisolone 20 mg/day was used because the signs of SLE, such as fever and decreased serum C3, levels, became aggravated on the fifth hospital day of acute myocardial infarction. Fatal cardiac rupture occurred on the twenty-second hospital day. At autopsy, extensive myocardial infarction with coronary artery thrombi and diffuse coronary arteritis were revealed. The rare clinical picture of a fatal cardiac rupture in the later phase of acute myocardial infarction and the precise dosage of prednisolone for her SLE are described.

Adult↗
PubMed1990

Anticholinergic action of disopyramide in intestinal smooth muscle of the guinea pig: inhibition of muscarinic receptors (M1 and M2).

Antimuscarinic actions of disopyramide were investigated by measuring the contractile responses of intestinal smooth muscles and ligand binding in cardiac and intestinal membrane preparations. Disopyramide caused a parallel shift of the dose-response curves for acetylcholine, McN-A-343, and carbachol to the right in the guinea pig taenia caeci; pA2 values were 5.4 for acetylcholine, 5.5 for McN-A-343 and 5.9 for carbachol. In the guinea pig ileum, disopyramide competitively antagonized acetylcholine in the contractile responses, having the pA2 value of 6.1. In microsomal fractions of the guinea pig taenia caecum and heart, disopyramide was capable of replacing 3H-QNB; K1 values were 7 x 10(-6) M for the taenia and 2 x 10(-6) M for the heart. These results suggest that disopyramide exerts antimuscarinic action through M1 and M2 receptors with a potency approximately 3 times greater for M2 than M1.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1990

Effects of KT-362, a new calcium release blocker, on vascular selectivity and hemodynamic actions in anesthetized dogs.

Pharmacological properties of 5-(3-((2-(3,4-dimethoxyphenyl)ethyl)-amino)-1- oxopropyl)-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a newly synthesized calcium release blocker, were studied by comparing its vascular selectivity and cardiovascular actions with those of verapamil, a calcium entry blocker. The relaxing effect of KT-362 in rabbit femoral and basilar artery strips contracted with norepinephrine was greater than that in aortic and coronary artery strips. In anesthetized mongrel dogs, KT-362 (0.1-3.0 mg/kg, i.v.) decreased the mean blood pressure, heart rate and total peripheral resistance in a dose-dependent manner, while cardiac output increased slightly despite a decrease in left ventricular pressure. This is consistent with the data on verapamil. Both i.a. and i.v. injections of KT-362 produced a marked dose-dependent increase in vertebral and femoral blood flow. Pretreatment of atropine, propranolol or diphenhydramine exerted no significant effect on the KT-362-induced vasodilation. Verapamil caused a marked increase in the vertebral and coronary blood flows after the injections, but only a slight increase in femoral blood flow. KT-362 at the dose of 10 mg/kg, i.v., had no significant effect on the PQ interval on the electrocardiogram in anesthetized dogs, but 0.1 mg/kg of verapamil increased this interval significantly. These results suggest that KT-362 has properties similar to calcium entry blockers such as verapamil on systemic hemodynamic actions except for the reactivity of vasculatures.

Anesthesia, Intravenous↗
PubMed1990

Effects of nitroglycerin on stable thromboxane A2 analogue-induced, nifedipine-resistant contraction in canine basilar artery.

The stable thromboxane A2 analogue, STA2, caused concentration-dependent contractions in the canine basilar artery. In Ca2(+)-free medium containing EGTA (0.1 mM) and nifedipine (10(-6) M), the addition of Ca2+ (2.5 mM) in the presence of STA2 (10(-8) M) caused a tonic contraction (nifedipine-resistant Ca2(+)-induced contraction). In the basilar artery, nitroglycerin did not significantly affect such nifedipine-resistant Ca2(+)-induced contractions, but nearly abolished the contraction in the coronary artery. The present experiments suggest that the regulatory mechanism of mobilized Ca2+ for the nifedipine-resistant Ca2(+)-induced contraction produced by STA2 in the basilar artery is different from that in the coronary artery.

Animals↗
PubMed1990

Liposomes as carriers of cisplatin into the central nervous system--experiments with 9L gliomas in rats.

The anticancer agent cis-diamminedichloroplatinum (cisplatin) has several disadvantages, including extreme nephrotoxicity, rapid binding to plasma proteins, and poor penetration of the central nervous system. In this study liposomes, which can cross the blood-brain barrier, were investigated for their potential in delivering therapeutic agents to brain tumors. Liposomes prepared from egg phosphatidylcholine and cholesterol in a 3:1 molar ratio were divided into 1-ml aliquots and either labeled with 14C or treated with horseradish peroxidase (HRP). The preparations were administered via the carotid artery to rats bearing 9L glioma. Radioactive uptake by brain tumor and normal tissues was measured with a liquid scintillation counter. The presence of HRP-containing liposomes in capillary endothelium and brain tumor cells was demonstrated by light and electron microscopic histochemical techniques. Thirty minutes after injection of 14C-labeled liposomes, radioactive uptake was higher in the spleen than in normal brain, brain tumor, liver, and kidney. Also uptake was greater in brain tumor and lower in kidney than that of cisplatin given alone. Light microscopy showed HRP-containing liposomes in brain tumor tissue 30 minutes after injection. On electron microscopy, liposomes were found to be regularly distributed in surface invaginations and vesicles of capillary endothelial cells. They were also observed within tumor cells. These results indicate that liposomes can penetrate the blood-brain barrier and hold promise as drug carriers in the treatment of brain tumors with cisplatin.

Animals↗
PubMed1990

[Dissolution and radio-opacity of apatite cement].

Dissolution and remineralization behaviors of self-setting apatite cement is organic acids and synthetic saliva and the effect of barium apatite (BaAp)on physicochemical and mechanical properties of the apatite cement were investigated. One-week solubility of several types of apatite cement was considerably smaller than that of commercially available dental cements in 1 mM of acetic, lactic and citric acids (pH4.0 at 37 degrees C). For example, the one-week solubility in citric acids was less than 4.5%. To investigate the dissolution behavior of the apatite cement in detail, two types of 45Ca labeled apatite cement were prepared. In one, the seed apatite was labeled with 45Ca(45Ca-HAp cement) and in the other the matrix apatite was labeled with 45Ca through use of 45Ca-DCPD (45Ca-DCPD cement). Solubility, estimated from the concentration of 45Ca released in 1mM of the organic acid was approximately zero for 45Ca-HAp cement, whereas the solubility of 45Ca-DCPD cement was similar to that of unlabeled cements. This suggests cat dissolution of the matrix apatite governs dissolution of the set cement. In synthetic saliva, the solution phosphate decreased with time once the set cement was introduced to the solution, whereas the solution calcium increased. The former finding suggests that some phosphate compounds precipitated in the synthetic saliva and the latter finding indicates that some portion of the set cement dissolved. The thermodynamic analysis of the solution compositions strongly suggests that remineralization is a major process and dissolution a minor one. In fact, in systhetic saliva labeled with 45Ca having a degree of supersaturation with respect to apatite comparable to rest saliva, 45Ca concentration in solution decreased once the cement pellet was introduced. This finding clearly suggests that the set apatite cement has the ability to remineralize but not to dissolve in synthetic saliva even if the degree of supersaturation with respect to apatite is relatively low. Addition of barium hydroxyapatite (BaAp) successfully bestowed clinically acceptable radio-opacity to the apatite cement. To accelerate the setting reaction which was retarded by Ba2+ released from BaAp at a lower pH during the first stage of spatulation, calcium hydroxyapatite (CaAp) was added to the cement mixture. At 20wt% of BaAp and 20wt% CaAp, the setting reaction proceeded at a neutral or weak alkaline pH, which is one of the most promising aspects of the apatite cement. The cement spaturated at L/P = 0.4 set within 10 minutes and its radio-opacity was comparable to or more than that of tooth enamel.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1990

[Weibull statistical analysis of bending strength data measured either in air or in distilled water for sintered hydroxyapatite ceramics coated on the metal substrate].

To assess the effects of H2O on the fracture stress of sintered hydroxyapatite (HAP) ceramics prepared by procedures similar to those used for HAP coated on the metal substrate, four-point bending tests were carried out at 0.5 mm/min either in air (20 C, R.H. 73%) or in distilled water (37 degrees C). Then, strength data obtained were analyzed using two-parameter weibull statistics. In each condition, the bending strength data gave a good fit to single-mode weibull distribution. Weibull analysis of the data gave weibull parameter m = 7.8, sigma 0 = 26.2 MPa in air and m = 8.1, sigma 0 = 18.5 MPa in distilled water, which were calculated assuming a surface flaw model. The mean value of bending strength was 27.3 MPa in air and 18.2 MPa in distilled water. These results indicated that a corrosive environment such as H2O affects fracture stress when measured at a constant stress rate. This effect is considered to be caused by slow crack growth of cracks, occurring at a loading level lower than those at which specimens will fail. Using the weibull distribution function estimated in this study, the effects of both dimension of specimen and stress distribution in the specimen on the mean fracture stress have been predicted.

Air↗
PubMed1990

[Estimation of fatigue parameter and life-time prediction using SPT diagram for hydroxyapatite coating layer in 37 degrees C distilled water].

Lifetime and survival probability of brittle materials under given conditions of stress distribution, environment and component size can be predicted using an SPT (Strenght-Probability-Time) diagram. The SPT diagram for sintered hydroxyapatite (HAP) coated on the metal substrate via the fused glass was drawn and the safe working stress in 37 degrees C distilled water was estimated. The dynamic fatigue test carried out in 37 degrees C distilled water gave the fatigue parameter n = 19 for sintered HAP. This parameter is constant except that it depends on material and environment, and the greater the value of n, the greater the resistance to fatigue failure. For sintered HAP, therefore, the resistance to fatigue failure under this wet condition is low. To draw the SPT diagram, anchor points were taken from the fracture stress and time-to-failure data measured at 1 mm/min. The SPT diagram obtained suggested that a lifetime of 20 years with survival probability of 99.9% required the safe working stress of less than 3.2 MPa. The effects of accuracy of fatigue parameter on the uncertainty in SPT diagram were estimated.

Corrosion↗
PubMed1990

[Effect of RU486 on collagenolytic enzyme activities in immature rat ovary].

To investigate the role of progesterone (P) in the ovulatory process, RU486 (RU) (10mg/kg), an antiprogesterone, was administered to PMS-hCG-treated immature female rats (22 days old). As for the collagenolytic enzymes (CE), the activities of BANA hydrolase and DNP peptidase were measured by using synthetic substrates alpha-N-benzoyl-DL-arginine-2-naphthylamide HCl and DNP Pro-Gln-Gly-Ile-Ala-Gly-Gln-D-Arg-OH, respectively. Serial assays were performed at 0, 2, 4, 6, 7, 8, 9, 10 and 12 hours after the hCG injection. In the control, the CE activities were significantly increased after the hCG injection at 8-9 hours in BANA hydrolase and 7-10 hours in DNP peptidase, respectively. By administering RU concomitant with hCG, the preovulatory increase in the CE activities was totally suppressed. Following the P(10mg/kg) injection at 4 hours after hCG and RU injections, the CE activities showed the greatest recovery, approaching the control range. In the ovulatory process of the rat ovary, P plays an important role through its regulatory effects on the collagenolytic enzymes, and this P effect seems to be most prominent around 4 hours after a LH surge.

Animals↗
PubMed1990

[Ultrastructure of capillary permeability in human brain tumor: disseminated and metastatic medulloblastoma].

The ultrastructure of the tumor vessels of primary cerebellar, subarachnoidal disseminated and extraneural metastatic medulloblastomas was studied. They were compared with those in glial, nonglial and metastatic brain tumors which have been previously reported. Twelve surgical specimens were examined. Seven tumors were limited to the vermis, the floor of the fourth ventricle and the cerebellar hemispheres. Four gross nodule seedings were demonstrated in the cerebral and spinal subarachnoid space. One metastasis was demonstrated in the subclavicular lymph node. Ultrathin section of those tumors and replica specimens were studied under the transmission electron microscope. The tumor vessels of primary medulloblastoma and glial tumors had nonfenestrated capillaries and were morphologically similar to normal brain capillaries. On the other hand, the tumor vessels of disseminated and metastatic medulloblastoma, nonglial tumors, and metastatic brain tumors had fenestrated capillaries. These findings were anticipated because the arachnoid membrane and lymph nodes have fenestrated capillaries. The presence of fenestration suggests that the tumor vessels of disseminated and metastatic brain tumors resemble the blood vessels found in normal arachnoid membrane and lymph nodes.

Adult↗