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Biomedical subjects

S Mihara

Publications and source records attributed to S Mihara.

At least 55 records · Page 3Linked to original sources
PubMed1996

Pharmacological studies on a new antihypertensive agent, S-2150, a benzothiazepine derivative: 1. Antinecrotic and antiarrhythmic effects in reperfused rat hearts.

S-2150 is a new 1,5-benzothiazepine derivative that inhibits [3H]diltiazem and [3H]WB4101 bindings to the membrane of rat tissue. The effects of S-2150 on ischemia/ reperfusion injury were studied in anesthetized rats. S-2150 reduced the myocardial infarct size (IS) induced by 20-min coronary artery occlusion followed by reperfusion. To evaluate reperfusion-induced ventricular tachycardia and fibrillation (VT, VF), we occluded the coronary artery for 4 min and then reperfused it. The incidence of arrhythmia was blocked by S-2150, and this effect offered protection against cardiac death. Prazosin did not modify the IS or incidence of reperfusion arrhythmias, but combined treatment with a noneffective dose of diltiazem showed significant cardioprotective effects. We also compared the direct effects of S-2150 and diltiazem on cardiac function and coronary perfusion flow using isolated rat hearts. Both drugs decreased mechanical function and increased coronary flow, with S-2150 being less cardiodepressive and more vasodilatory. S-2150 is cardioprotective at doses comparable to hypotensive doses even though its cardiodepressant effect is much weaker than that of diltiazem. This effectiveness may be partly explained by its dual characteristics: blocking the Ca channel and the alpha 1-adrenoceptor.

Adrenergic alpha-Antagonists↗
PubMed1996

Endothelin receptor antagonist triterpenoid, myriceric acid A, isolated from Myrica cerifera, and structure activity relationships of its derivatives.

As the first non-peptide endothelin receptor antagonist from a higher plant, a new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivatives (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.

Animals↗
PubMed1995

Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry.

Kuwanon G and H, isolated from the methanol extract of Morus bombycis, inhibited specific binding of [125I]gastrin-releasing peptide (GRP) to GRP-preferring receptors in murine Swiss 3T3 fibroblasts with Ki values of 470 and 290 nM, respectively. Kuwanon H was one order of magnitude less potent for inhibiting [125I]bombesin binding to neuromedin B (NMB)-preferring receptors in rat esophagus membranes. This compound antagonized bombesin-induced increases in the cytosolic free calcium concentration and GRP-induced DNA synthesis in Swiss 3T3 cells. Thus, kuwanon H, and possibly kuwanon G also, are specific antagonists for the GRP-preferring receptor and can be useful for studying the physiological and pathological role of GRP.

3T3 Cells↗
PubMed1995

Diagnostic revolution of microhematuria by real time confocal scanning laser microscope: Hyodo-Iino-Miyagawa method, third report.

The real time confocal scanning laser microscope provides excellent three-dimensional images free of out-of-focus information. The objective of this study was to evaluate the usefulness of the laser microscope for the diagnosis of microhematuria. Characteristics of the test were evaluated in 81 patients with definite causes of hematuria. 30 erythrocytes in urinary sediments were examined for each patient, and those in whom less than 20% of the erythrocytes were poikilocytes were considered to have urological diseases and those in whom 80% or more of the erythrocytes were poikilocytes to have nephritis. According to these criteria, the sensitivity and the specificity of the examination to nephritis were 100 and 98.1%. 91.4% of the patients with urological disease had the nonglomerular type. The time required for the examination was less than 2-5 min in samples containing 1-3 erythrocytes in one field under an ordinary light microscope (x400).

Cell Size↗
PubMed1994

Neurokinin A mimics the slow excitatory postsynaptic current in submucous plexus neurons of the guinea-pig caecum.

Single microelectrode voltage-clamp recordings were made from submucous neurons of the guinea-pig caecum. The slow excitatory postsynaptic current was compared with the currents induced by neurokinin A and substance P. The current induced by neurokinin A (100-300 nM) was associated with a decreased membrane conductance and reversed in polarity between -90 and -100 mV. The neurokinin A current was reduced by Co2+ (1-2 mM), but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In about 80% of the neurons, the current induced by substance P (100-300 nM) was associated with a decreased membrane conductance and did not reverse with hyperpolarization of the membrane potential up to -130 mV. The current was reduced by Co2+ (1-2 mM) and augmented by low Cl- (20-40 mM) solutions, but was not affected by Cs+ (1-2 mM) or Ba2+ (10-100 microM)-containing solutions. In about 20% of the neurons, the substance P current reversed in polarity between -100 and -120 mV. The slow excitatory postsynaptic current elicited by repetitive nerve stimulation (10-40 Hz, three to five pulses) was accompanied by a decreased membrane conductance, and reversed in polarity between -90 and -100 mV. The slow excitatory postsynaptic current was abolished by Co2+ (1-2 mM) or low Na+ (12 mM) solutions, but was not affected by Cs+ (1-2 mM), Ba2+ (10-100 microM) or low Cl- (20-40 mM) solutions. In such neurons, the neurokinin A current was reversed at approximately the same potential at which the slow excitatory postsynaptic current was reversed, while the substance P current was not reversed even by much stronger hyperpolarizations. It was concluded that the neurokinin A current was mainly due to depression of potassium conductances, while the substance P current resulted from both increased anion conductance and decreased potassium conductances. The conductance change underlying the slow excitatory postsynaptic current is similar to that caused by neurokinin A.

Animals↗
PubMed1994

Intervertebral disc amyloidosis: histochemical, immunohistochemical and ultrastructural observations.

Intervertebral discs selected at random from autopsies and surgical operations on herniated discs were examined for evidence of amyloid deposition. Amyloid deposits were detected in 53 (81.5%) of 65 autopsy cases. Discs from subjects over 50 years of age revealed a significantly high incidence of amyloid deposition. Among herniated discs, amyloid deposits were documented in 49 (75.4%) of 65 surgical specimens. The incidence of amyloid deposition in intervertebral discs increased with advancing age. Intervertebral disc amyloidosis consisted of amyloid deposits of three morphological types: linear amyloid deposits around the degenerating chondrocytes (perichondrocyte type), and nodular or band-like deposits in the annulus fibrosus (annulus fibrosus type) and nucleus pulposus (nucleus pulposus type). We suspect that the precursor protein of perichondrocyte type amyloid is derived from chondrocytes, and those of annulus fibrosus type and nucleus pulposus types are derived from the blood. The amyloid deposits were resistant to treatment with potassium permanganate. Immunohistochemically, the amyloid deposits reacted with antibody against amyloid P-component, but not with antibodies against AA, A kappa, A lambda, transthyretin or beta 2-microglobulin. Ultrastructurally, the amyloid deposits were composed of 10 nm-wide nonbranching fibrils. The amyloid in herniated discs had the same biochemical and immunohistochemical properties as those found in autopsy cases. The immunohistochemical characteristics of the amyloid deposits suggest that it derives from an, as yet, unknown precursor protein.

Adolescent↗
PubMed1994

Y2-receptor-mediated selective inhibition of slow, inhibitory postsynaptic potential in submucous neurones of guinea-pig caecum.

1. The subtype of neuropeptide Y receptor mediating the selective inhibition of the slow inhibitory postsynaptic potential (i.p.s.p.) of submucous neurones in guinea-pig caecum was investigated by use of conventional intracellular electrophysiological recording techniques. 2. Neuropeptide Y (NPY) (1-300 nM) was found to depress or abolish reversibly the slow i.p.s.p. evoked by focal stimulation of internodal fibre tracts. At low concentrations (1-30 nM), a reduction in the duration of the slow i.p.s.p. was often apparent before any inhibition of the amplitude of this synaptic potential. 3. These inhibitory effects of NPY were mimicked by peptide YY (PYY; 0.3-100 nM), NPY13-36 (1-300 nM) and NPY22-36 (10-100 nM); [Leu31,Pro34]NPY ([Pro34]NPY) and bovine pancreatic polypeptide (bPP) were without pre- or postsynaptic effects at concentrations of up to 300 nM. The IC50 +/- s.e. mean values for PYY, NPY, and NPY13-36 were 2.7 +/- 0.3, 7.8 +/- 2.1 and 30 +/- 4.8 nM, respectively, and were significantly different from each other. Thus, the apparent rank order of potency was PYY > NPY > NPY13-36 >> [Pro34]NPY and bPP. 4. In concentrations of up to 300 nM, NPY and its analogues had no depressant effects on the active and passive properties of the impaled neurone and did not affect the amplitude or duration of either cholinergic fast synaptic potentials or non-cholinergic, slow excitatory postsynaptic potentials (e.p.s.ps). Furthermore, none of these peptides altered the amplitude or time-course of changes in membrane potential induced by focal application of acetylcholine or noradrenaline. 5. It is, therefore, concluded that the selective inhibition of the slow i.p.s.p. is mediated by Y2-receptors,located presynaptically on noradrenergic nerve terminals.

Action Potentials↗
PubMed1994

Presynaptic inhibition by neuropeptide Y of slow inhibitory synaptic transmission in submucous neurones of guinea-pig caecum.

The occurrence and disposition of immunoreactivity for neuropeptide Y (NPY) was investigated in the submucosa of guinea-pig caecum. There were few NPY-immunoreactive neurones but intraganglionic varicose fibres were so numerous and strongly immunoreactive that some somata may have been obscured. In each neurone tested, exogenous application of NPY (1-100 nM) depressed the duration and amplitude of the slow inhibitory postsynaptic potential. In contrast, NPY (1-300 nM) had no effects on the resting membrane potential, input resistance and fast and slow excitatory synaptic transmission.

Animals↗
PubMed1994

Pharmacological characterization of a potent nonpeptide endothelin receptor antagonist, 97-139.

The endothelin (ET) receptor antagonist activity of 97-139 [27-O-3-[2-(3-carboxy-acryloylamino)-5-hydroxyphenyl]-acryloylo xy myricerone, sodium salt] was studied. In rat aortic smooth muscle A7r5 cells that express ETA receptors and human Girardi heart cells that express ETB receptors, 97-139 displaced specifically bound [125I]ET-1 with the Ki values of 1.0 +/- 0.2 and 1000 +/- 200 nM, respectively. The compound caused a concentration-dependent inhibition of ET-1-induced increases in intracellular Ca++ levels in A7r5 cells, but not in Girardi heart cells. 97-139 also inhibited ET-1-induced [3H]thymidine incorporation in A7r5 cells (IC50 = 0.92 +/- 0.48 nM). In rat aortic rings, 97-139 produced parallel rightward shifts in the ET-1 concentration-response curve without affecting the maximal contractile response (pA2 = 8.8 +/- 0.4). Administration of 97-139 (0.03-1.0 mg/kg) i.v. to pithed rats resulted in dose-dependent inhibition of the pressor response to ET-1. The in vivo potency of 97-139 was almost the same as that of BQ-123, although the potencies of 97-139 in binding assays and in vitro functional assays were about one order of magnitude higher than those of BQ-123. This discrepancy might involve high binding toward albumin in plasma because 95% plasma and 4% albumin reduced the apparent binding affinity of 97-139 by 22- to 24-fold, but not of BQ-123.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1993

Structure-activity relationships of an endothelin ETA receptor antagonist, 50-235, and its derivatives.

27-O-Caffeoyl myricerone (50-235) is a nonpeptide endothelin receptor antagonist which is highly selective for the endothelin ETA receptor subtype. In order to determine which functional groups in 50-235 are essential for its activity, we examined the potencies of 50-235 and its derivatives to inhibit [125I]endothelin-1 binding and endothelin-1-induced increase in the cytosolic Ca2+ concentration in rat aortic smooth muscle A7r5 cells. The results suggest that the 3-keto, 17-carboxyl and 27-caffeoyl groups in 50-235 are important for ETA receptor blocking activity. Modifications of the catechol ring of the 27-caffeoyl group influenced the affinity and the functional antagonist activity, but the effects were not parallel.

Animals↗
PubMed1993

The endothelin ETA receptor-specific effect of 50-235, a nonpeptide endothelin antagonist.

We characterized the endothelin receptor antagonist 27-O-caffeoyl myricerone (50-235), isolated from the bayberry Myrica cerifera, using rat aortic smooth muscle A7r5 cells that express ETA receptors and human Girardi heart cells that express ETB receptors. 50-235 concentration-dependently inhibited 125I-ET-1 binding to A7r5 cells with Ki of 51 +/- 12 nM, while it had no effect on 125I-ET-1 and 125I-ET-3 bindings to Girardi heart cells. Also in affinity cross-linking studies with 125I-ET-1, 50-235 inhibited labeling of a protein of M(r) = 67,000 in A7r5 cells, but did not inhibit labeling of two proteins with M(r) values of 70,000 and 46,000 in Girardi heart cells. Functionally, 50-235 inhibited the ET-1-induced increase in cytosolic free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner (IC50 = 11 +/- 2 nM) in A7r5 cells. On the other hand, this compound had no effect on the basal level of [Ca2+]i and the high K(+)- and bombesin-induced increases in [Ca2+]i in A7r5 cells, nor on the ET-1-induced increase in [Ca2+]i in Girardi heart cells. Also, 50-235 inhibited ET-1-promoted mitogenesis of A7r5 cells. Thus, we conclude that 50-235 is a specific endothelin A receptor antagonist that could be very useful for elucidating the physiological and pathophysiological significance of ET.

Animals↗
PubMed1993

Dilated cardiomyopathy in a patient receiving continuous ambulatory peritoneal dialysis.

We describe a unique case of a 10 year old girl with dilated cardiomyopathy who has been receiving continuous ambulatory peritoneal dialysis. She responded to treatment with a beta 1-agonist. We note that electrocardiography and echocardiography are effective for early recognition of the onset of dilated cardiomyopathy and that a thallium scan should be performed to assess the severity of dilated cardiomyopathy in patients with chronic renal insufficiency.

Adrenergic beta-Agonists↗
PubMed1993

[Renal cell carcinoma with contralateral adrenal metastasis: a case report].

A case of contralateral adrenal metastasis of renal cell carcinoma is reported. The patient was a 54-year-old male, who underwent a right radical transperitoneal nephrectomy for renal cell carcinoma, and had been administered interferon alpha intramuscularly. Nine months after the operation computerized tomography revealed the presence of an adrenal mass on the left side, undetected at nephrectomy, which suggested that the renal cell carcinoma had metastasized. A left adrenalectomy was performed. Histologically, the mass was identical to metastasis of renal cell carcinoma. The patient was administered supplementary hydrocortisone and was well 3 months after the adrenalectomy with no evidence of recurrence or other metastasis. This is the 24th case of contralateral adrenal metastasis of renal cell carcinoma in the Japanese literature.

Adrenal Gland Neoplasms↗
PubMed1992

A novel non-peptide endothelin antagonist isolated from bayberry, Myrica cerifera.

A potent non-peptide ET receptor antagonist, myriceron caffeoyl ester (50-235), was isolated from the bayberry, Myrica cerifera. This compound selectively antagonized specific binding of [125I]ET-1, but not of [125I]ET-3, to rat cardiac membranes, ET-1-induced increase in the intracellular free calcium concentration in Swiss 3T3 fibroblasts, and ET-1-induced contraction of rat aortic strips. Thus, 50-235 is the first non-peptide ET(A) receptor antagonist. This compound can be useful for studying the physiological role of endothelin and exploring its role in various diseases.

3T3 Cells↗