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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 667 records · Page 37Linked to original sources
PubMed1986

Effects of calcium, calcium entry blockers and calmodulin inhibitors on atrioventricular conduction disturbances induced by hypoxia.

Effects of hypoxia on atrioventricular conduction were investigated in the Langendorff-perfused isolated heart of the rabbit with various extracellular calcium concentrations ([Ca2+]) as well as in the presence of verapamil, nifedipine, N-(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7) and chlorpromazine. The prolongation of the atrio-His (AH) interval by hypoxia for 7 min was greater with increasing [Ca2+]o ranging from 1.2 to 5.2 mM. At [Ca2+]o of over 3.2 mM under hypoxic conditions, AH block of the Wenckebach type was observed in some cases. Verapamil (5 X 10(-8) M) and nifedipine (5 X 10(-8) M) caused a significant prolongation of AH intervals before hypoxia. However, the intensity of AH prolongation due to hypoxia was significantly attenuated in the presence of the calcium entry blocker, and AH block was not induced even at 3.2 mM [Ca2+]o. W-7 (5 X 10(-6) M) and chlorpromazine (10(-6) M) did not affect the AH intervals before hypoxia. The hypoxia-induced prolongation of the AH interval or AH block was prevented in the presence of these drugs. W-5, a chlorine-deficient derivative of W-7, showed no protection against hypoxia-induced AV nodal conduction disturbances. These findings suggest that hypoxia-induced AV nodal conduction disturbance is explained, at least in part, by the electrical uncoupling of nodal cells, probably due to the calcium overload. This conduction disturbance is protected by calcium entry blockers or by calmodulin inhibitors, but the mode of protective action is not the same for these different categories of drugs.

Animals↗
PubMed1986

The mode of vasorelaxant action of 2-aminoisoquinoline, 1.3 (2H.4H)-dione, a novel 'intracellular calcium inhibitor'.

In rabbit aorta, pretreatment with 2-aminoisoquinoline, 1.3 (2H.4H)-dione (AQ, 10(-5) M and 10(-4) M) shifted the concentration-response relationship to noradrenaline (NA, 10(-9) M to 10(-4) M) in a parallel manner whereas the agent (10(-4) M) failed to affect the response to potassium and only slightly depressed Ca2+-induced contractions in a Ca2+-free medium in the presence of K+ (40 mM). Ca2+-entry blockers such as nifedipine and diltiazem (10(-6) M and 10(-5) M) had very weak or no apparent effects on the response to NA but markedly attenuated or abolished the K+- and Ca2+-induced contractions. Following incubation of tissues for 15 min in a Ca2+-free medium with low EGTA (0.01 mM) and methoxyverapamil (D600, 10(-5) M), NA (3 X 10(-7) M) caused a phasic (transient) contraction and the subsequent application of Ca2+ (2mM) resulted in a tonic contraction. This NA-induced, Ca2+-dependent, D600-insensitive contraction was inhibited by AQ (10(-5) M and 10(-4) M) in a concentration-dependent manner. This suggests that the inhibitory action of AQ may be related to Ca2+ entry through specific receptor activated pathways. Following incubation of tissues for 30 min in a Ca2+-free medium with high EGTA (2.0 mM), NA (10(-5) M) caused a contraction of rabbit aorta which is dependent upon release of intracellular Ca2+, but the response was 50% to 60% less than that in a normal medium. This contraction was inhibited by AQ (10(-5) M and 10(-4) M) and nitroglycerin (10(-5) M) but not by nifedipine or diltiazem. The inhibitory action of combined treatment with AQ and nitroglycerin (10-5 M) on the response to NA was not different from that of either agent alone. 5 These results suggest that AQ may have inhibitory actions on the release of intracellular Ca2+ and also on Ca2+-entry through D600-insensitive, receptor-activated Ca2+ pathways in rabbit aorta.

Aminoquinolines↗
PubMed1986

Mechanism of barium-induced contraction in the vascular smooth muscle of rabbit aorta.

In a solution containing 1.5 mM Ca2+, cumulative application of 0.3-10.0 mM Ba2+ induced a concentration-dependent contraction of the rabbit aorta. This contraction was reduced by the Ca2+ channel inhibitors, verapamil (10(-6) M), nifedipine (10(-7) M) and lanthanum (2.0 mM), and was potentiated by the Ca2+ channel facilitator, Bay K8644 (10(-7) M). In a Ca2+-free solution containing EGTA (1.0 mM), cumulative application of Ba2+ still induced a concentration-dependent contraction, the maximum contractile tension of which was comparable to that in the presence of 1.5 mM Ca2+. The Ba2+-induced contraction which was not dependent on the external Ca2+ was also inhibited by verapamil, nifedipine and lanthanum and was potentiated by Bay K8644. A high concentration (65.4 mM) of K+ potentiated this Ba2+-induced contraction whereas noradrenaline (10(-6) M) did not have such an effect. In order to deplete the releasable Ca2+ store in the cell, the muscle strip was treated with noradrenaline (10(-6) M) and/or caffeine (20.0 mM) in a Ca2+-free solution. In such a Ca2+-depleted muscle, Ba2+ still induced a contraction of a similar magnitude to that without such treatment. Further, the second application of Ba2+ in a Ca2+-free solution induced a similar contraction to that induced by the first application of Ba2+. These results suggest that Ba2+ depolarizes the cell membrane and opens the voltage-dependent Ca2+ channels resulting in a Ca2+ influx in the presence of Ca2+. In the absence of external Ca2+, Ba2+ may enter the cell through the voltage-dependent Ca2+ channels and induce contraction without mobilizing the Ca2+ store which is sensitive to noradrenaline and caffeine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Electromechanical effects of okadaic acid isolated from black sponge in guinea-pig ventricular muscles.

Okadaic acid is a monocarboxylic acid with a unique molecular structure of C44H66O13. Okadaic acid, at concentrations above 10(-5) M, caused a dose-dependent increase of contractile force in guinea-pig isolated ventricular muscles. The increase of contractile force by okadaic acid (1-4 X 10(-5) M) was accompanied by a prolongation of action potential duration (a.p.d.), while a.p.d. was shortened by okadaic acid at above 10(-4) M. The okadaic-acid-induced changes in contractile force and a.p.d. were abolished by pre-treatment with verapamil (2 X 10(-6 M) or nifedipine (10(-6) M). In a low-Ca2+ medium (0.12 mM), the contractile response to okadaic acid (4 X 10(-5) M) was inhibited, whereas the a.p.d. was more prolonged by the drug than in a control medium (containing 1.2 mM-Ca2+). In a low-Na+ (70 mM) medium or in a low-Na+ (70 mM) and low-Ca2+ (0.12 mM) medium both the contractile force and a.p.d. were unaffected by okadaic acid (4 X 10(-5) M). The positive inotropic effect of okadaic acid (4 X 10(-5) M) was not inhibited by treatment with tetrodotoxin (TTX, 2 X 10(-6) M) or with ryanodine (2 X 10(-6) M). In voltage-clamp experiments using a single sucrose-gap technique, okadaic acid (4 X 10(-5) M), caused a significant increase of slow inward current, while it did not affect the net outward current. These findings suggest that okadaic acid has a positive inotropic effect on the heart, probably due to the enhancement of slow Ca2+ and/or Na+ inward current through the cell membrane.

Action Potentials↗
PubMed1986

Effect of nicorandil, N-(2-hydroxyethyl)nicotinamide nitrate, a new anti-anginal agent, on contractile responses to alpha-1- and alpha-2-adrenoceptor agonists in isolated rabbit aorta.

Effects of nicorandil on contractile responses to alpha 1- and alpha 2-adrenoceptor agonists were examined in isolated rabbit aorta. Nicorandil (10(-6) or 10(-5) M) inhibited contractile responses to clonidine (CL) and BHT-920 in a concentration-dependent manner, but had no effect on the response to methoxamine (MO). Nifedipine (10(-6) and 10(-5) M) had no significant effect on responses to CL and MO, but it had a noticeable inhibitory effect on the response to BHT-920. In tissues pretreated with phenoxybenzamine, nicorandil (10(-5) M) inhibited the residual response to MO, and nifedipine (10(-5) M) inhibited responses to MO and CL. The relationship between maximum contraction and percent receptor occupancy was found to be nonlinear for MO, but was near linear for CL and BHT-920. The inhibitory effect of prazosin (pA2 of about 9) on MO and CL was much greater than that of yohimbine (pA2 of about 6). Nicorandil had no apparent or slight inhibitory effect on responses to potassium and Ca2+, and this inhibitory effect was much less than that of nifedipine. These results indicate that the responses induced by MO, CL, and BHT-920 in the rabbit aorta are due to activation of alpha 1-adrenoceptors. It is also suggested that nicorandil minimally affects voltage-dependent Ca2+ influx and that differential effects of nicorandil on the responses to alpha 1 and alpha 2 agonists may be the result of differences in the amount of receptor reserve that exist for MO, CL, and BHT-920 in this blood vessel.

Adrenergic alpha-Agonists↗
PubMed1986

Sympathetic nerve activity, plasma renin activity and water-sodium balance in obese patients with essential hypertension.

Studies were conducted to evaluate the role of water-sodium metabolism on the hypertensive mechanisms in obese patients with essential hypertension (EHT). The obesity index correlated positively with the mean arterial pressure, plasma volume, extracellular fluid volume or total exchangeable sodium, and negatively with plasma noradrenaline concentration or plasma renin activity in EHT. Hypotensive effects of sodium restriction (Na 35 mEq, K 75 mEq) or the natriuretic response to infused dopamine (3 micrograms/kg/min) was remarkable in obese EHT. Fractional excretion of sodium (FENa), which reflects the renal tubular reabsorption of sodium, was significantly lower in obese EHT than that in non-obese or mildly obese EHT. Urinary excretion of free dopamine (UDA) had a positive relationship with simultaneously measured urinary excretion of sodium or FENa. In addition, UDA correlated positively with the obesity index in patients whose weight was under 115% of the ideal weight. On the contrary, the relation between the two parameters was significantly negative in patients whose weight was over 115% of the ideal weight. These findings suggest that the expansion of body fluid volume and sodium, which might result from the blunted natriuretic ability, at least in part, due to an attenuation of the renal dopaminergic activity, play an important role of the hypertensive mechanisms in obese EHT.

Adult↗
PubMed1986

Depolarizing effects of glycyrrhizin-derivatives relating to the blend effects with paeoniflorin in mouse diaphragm muscle.

Glycyrrhizin (GLR) and its newly synthesized derivatives, deoxoglycyrrhetol dihemisuccinate (I), deoxoglycyrrhetol dihemiphthalate (II), and the related compounds, carbenoxolone and glycyrrhetinic acid hemiphthalate (III), were assayed with or without paeoniflorin (PF) in mice diaphragm muscles. GLR-derivatives per se blocked the nerve-stimulated twitch tensions with the following order of potencies: carbenoxolone = III greater than II = I greater than GLR. The potencies paralleled the extent of muscle depolarization except in the case of I. GLR and I only increased muscle conductance. The blocking effects by GLR-derivatives per se on twitch responses are, therefore, can be explained by depolarization of muscle membranes and not by membrane conductance change. When carbenoxolone, II or GLR were blended with PF, the potentiation of the blocking effects observed may be related to the muscle depolarization rather than by the increase in membrane conductance.

Animals↗
PubMed1986

Pseudomyxoma peritonei: effect of chronic continuous immunotherapy with a streptococcal preparation, OK-432 after surgery.

Three cases of pseudomyxoma peritonei with ovarian neoplasma were treated by adjunctive immunotherapy with OK-432 after surgery. In 2 of the 3 cases, the periods of intramuscular injection of OK-432 were 11 and 16 months, respectively, and the 2 patients remain clinically free from evidence of disease, 7 and 6 years after surgery. The third patient is still undergoing treatment, with no evidence of recurrence at 4 months after surgery. These results, although for a small number of patients, clearly suggest that adjunctive immunotherapy with OK-432 may be suitable for treating pseudomyxoma peritonei of ovarian tumor origin.

Aged↗
PubMed1986

Comparison of nephritogenic glycopeptide, nephritogenoside, isolated from rat glomerular basement membranes with other basement membrane components.

Nephritogenic glycopeptide, nephritogenoside, is a minor component of basement membranes (the yield: 2-3 micrograms/kidney), and in homologous animals causes chronic glomerulonephritis. Nephritogenoside was compared to other basement membrane components including collagenous and noncollagenous glycoproteins. In limited pepsin digests of rat renal cortices, nephritogenoside was separable from type IV collagen by DEAE-cellulose column chromatography, although these two substances showed immunological cross-reactivity each other. Nephritogenoside did not immunologically cross-react with laminin and fibronectin by direct or inhibition enzyme immunoassay. These results indicate that nephritogenoside is different from basement membrane glycoproteins such as laminin and fibronectin and that nephritogenoside can be isolated from type IV collagen.

Animals↗
PubMed1986

Glycyrrhetic acid inhibits tumor-promoting activity of teleocidin and 12-O-tetradecanoylphorbol-13-acetate in two-stage mouse skin carcinogenesis.

Glycyrrhetic acid suppressed tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells and down-regulation of the epidermal growth factor receptor. Glycyrrhetic acid inhibited the promoting activity of both 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA). The percentage of tumor-bearing mice in the group treated with DMBA plus teleocidin was 88% at week 18, whereas that in the group treated with DMBA plus teleocidin and glycyrrhetic acid (10 mumol/painting) was 6%. Similarly, the percentage of tumor-bearing mice of the group treated with DMBA plus TPA was 97% at week 20, whereas that of the group treated with DMBA plus TPA and glycyrrhetic acid was 40%. Therefore, glycyrrhetic acid was proved to inhibit the activity of two different tumor promoters, teleocidin and TPA, in mouse skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

[Ultrastructure of capillary permeability in human brain tumors. 2: Mechanisms of contrast enhancement in gliomas].

In order to elucidate the mechanism of contrast enhancement on computerized tomography (CT), the alteration of capillary permeability was studied in 3 cases of medulloblastoma, 2 cases of ependymoma, 5 cases of glioblastoma and 5 cases of astrocytoma. The surgical specimens were studied with conventional ultrathin section and freeze-fracture replica techniques. Contrast enhancement on CT scan defined in order of medulloblastoma, ependymoma, glioblastoma and astrocytoma. In the medulloblastomas and glioblastomas, the cell junctions of the capillaries were short, elongated, and, in fact open. Other capillary abnormalities included endothelial hyperplasia with extensive vesicular formation, surface infolding of endothelial cells, irregularity of the basal lamina, and a large extravascular space. Tight junctions were seen as one or twe strands. These tight junctions presented irregular lining of intramembranous particles. In the astrocytomas, the blood vessels appeared relatively normal, and the tight junction were seen as networks of seven strands. The particles lines were not disrupted. In the ependymomas, the tight junctions in one area were seen as a network of six strands, but in the other areas as three strands, and the fenestrae were observed in the replicas but not confirmed in the ultrathin sections. The conclusion drawn from this study is that osmotic opening of the tight junctions that have fewer strands play an important role in the marked contrast enhancement of the gliomas, in addition to transcellular transport of increased pinocytotic vesicles and fenestrations. The irregular basal lamina and large perivascular space also increase extravasation of contrast medium.

Adult↗
PubMed1986

[Ultrastructure of capillary permeability in human brain tumors. 3: Mechanisms of contrast enhancement in non-glial tumors].

In order to elucidate mechanisms of contrast enhancement on computed tomography observed in non-glial tumors, tumors vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The materials were obtained from surgically removed specimens in 19 cases of tumors (6 of meningioma, 6 of hemangioblastoma, 5 of pituitary adenoma, and 2 of acoustic neurinoma). The following results were obtained. The common findings of these non-glial tumor vessels in ultrathin preparations were surface infoldings, increased pinocytotic vesticles and many fenestrations of endothelial cells, irregularity of basal laminae, and enlarged perivascular spaces. In freeze-fracture replicas of vascular endothelium, pinocytotic vesicles and fenestrations were 22 and 26 per micron2 on the average respectively. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. As for the each non-glial tumor, menigiomas showed endothelial thickness and finger-like projections, variable lengths of tight junctions and marked enlargement of perivascular space which contained many collagen fibrils. Thinning of endothelium and many fenestrations were observed in hemangioblastomas, pituitary adenomas, and acoustic neurinomas. Fenestrations were most frequently observed in pituitary adenomas. The results indicate that extravasation of contrast material through fenestrations has an important role in marked contrast enhancement of non-glial tumors, in addition to the osmotic opening of tight junctions by contrast material. The irregular basal lamina and large perivascular space may also contribute to an increased extravasation of contrast material.

Adenoma↗
PubMed1986

[Ultrastructure of capillary permeability in human brain tumors--4: Cerebral edema associated with meningiomas].

The cerebral edema, as judged by computed tomographic scan, associated with supratentorial meningiomas was assessed in 43 cases. No relationship to the occurrence or the degree of edema could be established with respect to meningioma location and histological type. The larger the meningioma, the more likely the presence of and the severity of cerebral edema. The materials were obtained from surgically removed specimens in 6 cases of meningiomas with and without associated cerebral edema, and tumor vessels were studied with conventional ultrathin section and freeze-fracture replica techniques. The characteristic findings of these tumor vessels were thinning of endothelium and many fenestrations, short and in fact open tight junctions. Tight junctions between endothelial cells were composed of one or two strands which appeared to be a discontinuous array of particles. The ultrastructural appearance of tumor vessels is similar to that seen in meningiomas with and without associated cerebral edema.

Adolescent↗