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Biomedical subjects

M Kusunoki

Publications and source records attributed to M Kusunoki.

At least 199 records · Page 11Linked to original sources

The effects of sodium valproate on plasma somatostatin and insulin in humans.

To determine the role of gamma-aminobutyric acid (GABA) in islet tissue, sodium valproate (1600 mg/day) was administered for 6 days to 10 normal subjects and 1 patient with a somatostatinoma. Plasma valproate concentrations reached a steady state by the third day accompanied by elevation of plasma GABA concentrations. Sodium valproate administration resulted in a 40% decrease in plasma somatostatin concentrations in the normal subjects and a 63% decrease in the somatostatinoma patient, respectively, compared to the response to placebo. Plasma C-peptide concentrations did not change in any subject. Fasting blood glucose levels decreased in the somatostatinoma patient during sodium valproate administration. These results suggest that endogenous GABA may play some role in the release of somatostatin, but not in the release of insulin.

Adult↗

Crystallization of the complexes between M315 idiotope and its monoclonal anti-idiotopic antibody Fab fragment.

The Fab fragment of a monoclonal anti-idiotopic antibody against M315 has been isolated and its complexes with Fv and Fab' fragment of M315 have been crystallized by using poly(ethylene glycol) 6000 or ammonium sulfate. X-ray diffraction photographs showed that the crystal of the complex with Fv diffracts better than that with Fab'. The Fv-complexed crystal was shown to be tetragonal I4, with cell dimensions a = 152 A and c = 69 A, and to contain one complex molecule of about 75,000 molecular weight in the crystallographic asymmetric unit.

Animals↗

Differences between muscular receptors and neural receptors for cholecystokinin-octapeptide in the guinea-pig gallbladder.

To investigate the differences between muscular and neural receptors for cholecystokinin-octapeptide (CCK-OP) in the guinea-pig gallbladder, we studied the effects of dibutyryl cyclic GMP (dbc GMP) on CCK-OP-evoked contraction and [3H]acetylcholine (ACh) release. 10(-3) M dbc GMP significantly reduced CCK-OP (10(-8) M)-evoked contractions without affecting the peptide-induced [3H]ACh release. It is suggested that there are two types of CCK-OP receptors in the guinea-pig gallbladder (dbc GMP-sensitive muscular receptors and dbc GMP-insensitive neural receptors).

Acetylcholine↗

Adenosine 5'-triphosphate release evoked by electrical nerve stimulation from the guinea-pig gallbladder.

The endogenous release of adenosine 5'-triphosphate (ATP) from strips of guinea-pig gallbladder during transmural stimulation (TS) was measured with a firefly luciferine-luciferase reaction. TS (15V, 1 ms, 0.5-5 Hz, for 1 min) caused a rapid and marked increase of ATP release in a frequency-dependent manner. Both ATP release and contractions evoked by TS (15 V, 5 Hz, 1 ms) were completely abolished in Ca-free medium. BaCl2 (3 X 10(-3) M), a direct muscle stimulant, produced almost the same degree of contractile tension as TS (15 V, 5 Hz, 1 ms) while the ATP release induced by BaCl2 was significantly reduced to about 60 percent of that induced by TS. Atropine (10(-6) M) significantly reduced TS-evoked contraction without affecting ATP release. It was suggested, therefore, that some of the ATP release induced by TS was of neural origin. Theophylline (a P1-purinoreceptor antagonist) 10(-6) M, quinidine (a non-specific P2-purinoreceptor antagonist) 10(-6) M and apamin (a potassium channel blocking agent) 10(-8) M had no effects on TS-evoked contraction and ATP release, suggesting the absence of a presynaptic autoregulatory mechanism of ATP release in the guinea-pig gallbladder.

Adenosine Triphosphate↗

Choledochal cyst. Its possible autonomic involvement in the bile duct.

The properties of the choledochal cyst were compared with those of the normal common bile duct. Cholecystokinin-octapeptide and a high concentration of acetylcholine produced smaller contractions in the strips of the narrow portion of the cyst than in the strips of the dilated portion and the normal common bile duct. Nicotine did not cause contractions in the strip of the narrow portion of the cyst. gamma-Aminobutyric acid (GABA) induced atropine-sensitive, tetrodotoxin-sensitive contractions in the bile ducts through bicuculline-sensitive, furosemide-sensitive GABAA receptors located on the postganglionic cholinergic neuron. The GABA did not induce contractions in the narrow portion of the cyst. The number of ganglion cells was decreased markedly in the same portion. These findings suggest that the choledochal cyst has postganglionic neural dysfunction. This character may be one of the causes of cyst formation.

Acetylcholine↗

Progesterone inhibits the contractile motility of the guinea pig gallbladder.

We studied the effects of progesterone on the contractile motility of the guinea pig gallbladder in vitro. Carbachol (10(-6) M) induced contractions were reduced by the pretreatment with progesterone (10(-8)-10(-6) M) in a dose-dependent manner. Concentration-response curves for carbachol, histamine and CCK-OP showed inhibition by progesterone (5 X 10(-7) M). These results suggest that progesterone has a direct inhibitory effect on gallbladder smooth muscle. Contractile responses to potassium (10-60 mM) or calcium (0.4-3.2 mM), which were thought to activate the contractile machinery by increasing the influx of extracellular calcium, were not affected by the pretreatment of progesterone. The direct inhibitory effects of progesterone on gallbladder smooth muscle might be explained by the inhibition of calcium release from the intracellular storage sites.

Animals↗

Dual action of cholecystokinin-octapeptide on the guinea pig antrum.

We examined the mechanism of action of cholecystokinin-octapeptide (CCK-OP) on longitudinal strips of the lesser and greater curvatures of the guinea pig antrum. In the strips of the lesser curvature, CCK-OP produced a concentration-dependent tonic contraction, which was significantly reduced by atropine, but not by tetrodotoxin. In contrast, CCK-OP caused a relaxation of the preparation of the greater curvature in a concentration-dependent manner. The relaxation induced by the peptide was enhanced by atropine, whereas it was blocked by tetrodotoxin. Propranolol, phentolamine, desensitization to adenosine-5'-triphosphate, and desensitization to vasoactive intestinal polypeptide had no effect on CCK-OP-induced relaxation. Cholecystokinin-octapeptide evoked the release of acetylcholine from strips of both sides, and it was not blocked by tetrodotoxin. These findings indicate that the mechanism of action of CCK-OP on the lesser curvature differs from that on the greater curvature. The peptide seems to act directly on smooth muscle cells and to stimulate cholinergic neural activity by sodium channel-independent mechanisms. Additionally, nonadrenergic inhibitory neurons appear to be activated by CCK-OP in the greater curvature.

Animals↗

Overproduction and preliminary X-ray characterization of aspartate aminotransferase from Escherichia coli.

The aspartate aminotransferase of Escherichia coli was overproduced in cells after genetic manipulation, and was crystallized from a polyethylene glycol solution, pH 7.0. The crystals obtained were of good quality and had diffractions extending beyond 2.4 A. The space group and unit cell dimensions were determined with a precession camera and a four-circle diffractometer to be C222(1), and a = 157.1 A, b = 85.5 A, and c = 79.7 A, respectively. Only one protein subunit is contained in an asymmetric unit.

Aspartate Aminotransferases↗

Two crystalline forms of a lectin from Flammulina veltipes.

A lectin from Flammulina veltipes (Enoki-dake) has been crystallized in a form suitable for crystallographic structure analysis. Two types of crystals were grown: one from polyethylene glycol 6000 solution at pH 7 and the other from ammonium sulfate solution at pH 7. The latter type is more suitable for the crystallographic investigations because of its high resolution X-ray diffraction and smaller number of asymmetric molecules.

Agaricales↗

Receptor interactions of a series of imidazolines: comparison of the alpha 2-adrenoceptors between the rabbit vas deferens and guinea pig ileum.

A series of imidazolines and norepinephrine were used to characterize and differentiate the presynaptic alpha 2-adrenoceptors in the rabbit vas deferens and the guinea pig ileal longitudinal muscle using pharmacological procedures. Based on pEC50-values (the negative log of the 50% effective concentration) for each imidazoline, a rank order of potency of p-aminoclonidine greater than oxymetazoline greater than or equal to clonidine greater than naphazoline greater than phentolamine was obtained in the rabbit vas deferens and an order of p-aminoclonidine greater than clonidine greater than naphazoline greater than oxymetazoline was obtained in the guinea pig ileum. In the rabbit vas deferens, phentolamine, which is generally considered to be a competitive alpha 1- and alpha 2-adrenoceptor antagonist, acted as a full alpha 2-adrenoceptor agonist. The dissociation constants of oxymetazoline and yohimbine were significantly lower in the rabbit vas deferens than in the guinea pig ileum. These results suggest that the presynaptic alpha 2- adrenoceptors in these tissues are different. Furthermore, the pKB-value of yohimbine against norepinephrine was significantly one log unit lower than those obtained using a series of imidazolines. Data from our studies add to increasing evidence of the existence of high and low affinity binding sites on the alpha 2-adrenoceptors in the rabbit vas deferens.

Animals↗

[Gastrointestinal polyposis and hereditary large bowel cancer].

Hereditary large bowel cancer is roughly divided into the hereditary gastrointestinal polyposis (HGIP) that is including adenomatosis coli (AC), Peutz-Jeghers syndrome and juvenile polyposis, and non-polyposis familial large bowel cancer (NPF) which is including cancer family syndrome and its related conditions. In the HGIP, AC is most frequent and of highest risk of large bowel cancer, and epidemiological method of approach to patients has been well studied. NPF, however, has been insufficiently studied because of lacking of distinctive marker as seen in the polyposis in spite of that it may be actually present much more frequently than AC. In order to extract NPF from the general large bowel cancer group, the marker or criteria for it has been studied. The factors besides family history presently considered to be useful for detecting NPF are multiple cancers, proximal cancer, association of multiple adenoma and young (50 years or younger) onset of the disease.

Adenoma↗

Cholecystokinin octapeptide-evoked [3H]acetylcholine release from guinea pig gallbladder.

Cholecystokinin-octapeptide (CCK-OP) produced a contractile response in isolated guinea pig gallbladder; the response consisted of scopolamine-sensitive and scopolamine-insensitive components, neither of which were affected by tetrodotoxin or hexamethonium. In the presence of tetrodotoxin, CCK-OP evoked [3H]acetylcholine (ACh) release from strips of gallbladder in a concentration-dependent manner. These results suggest that CCK-OP acts at two sites in the guinea pig gallbladder, viz. the smooth muscle cell and the postganglionic cholinergic nerve terminal.

Acetylcholine↗

Imaging platelet deposition on Dacron bifurcation grafts in man: quantification by a dual-tracer method using 111In-labeled platelets and 99mTc-labeled human serum albumin.

A dual tracer technique using 111In-labeled platelets and 99mTc-labeled human serum albumin was applied to evaluate the thrombogenicity of Dacron bifurcation arterial grafts. The level of platelet accumulation over the whole of the graft was estimated from the ratio of 111In-platelet radioactivity deposited on the vascular wall to these radioactivity circulating in the blood pool, i.e., the platelet-accumulation index (PAI). Furthermore, the PAI value was calculated for each pixel in digitized images and the PAI distribution image (PAI image) was reconstructed. Eighteen patients with DeBakey knitted Dacron bifurcation grafts and 11 normal volunteers were studied. Of the 18 patients, 11 had no graft occlusion (group I) and the remaining 7 (group II) had occlusion. The mean PAI value (+/- SD) over the whole of the graft in group I was 32.6% +/- 33.7% as compared to -8.8% +/- 4.5% in the control group (P less than 0.01). In group I, the PAI value over the entire graft decreased with the age of the graft (r = -0.763; P less than 0.01). In contrast, in group II, platelet accumulation did not diminish with time and persisted beyond the time of which platelet accumulation was no longer found in group I. Moreover, analysis of the PAI images revealed enhanced platelet accumulation on the proximal part of the graft to be more frequent in group II than in group I (6/7 vs 0/11; chi 2c = 10.55; P less than 0.005). The method used for platelet imaging in the present study may be useful in the study of platelet reactions on Dacron arterial prostheses.

Aged↗

Actions of 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy) benzeneacetamide (KF4317) and labetalol on alpha- and beta-adrenoceptors.

Blocking activities of alpha- and beta-adrenoceptors by 4-(2-hydroxy-3-[(1-methyl-3-phenylpropyl)amino]propoxy)benzeneacetamide (KF4317) were tested on the isolated muscles, compared with the action of labetalol. In blocking the beta 1-adrenoceptor, KF4317 was almost as active as labetalol. KF4317 was about 1/10th as potent as labetalol in blocking the beta 2-receptor. KF4317 was beta 1-adrenoceptor selective. KF4317 was about 1/50th as potent as labetalol in blocking the alpha 1-receptor. KF4317 did not interact with the alpha 2-adrenoceptor in concentrations up to 10(-5) M. The present results indicate that KF4317 is a selective beta 1- and alpha 1-adrenoceptor blocker, though the alpha 1-adrenoceptor blocking action is weak.

Animals↗

Crystallographic study of cytochrome c553 from Desulfovibrio vulgaris Miyazaki.

Cytochrome c553 from the sulfate-reducing bacterium, Desulfovibrio vulgaris Miyazaki, has been crystallized. The combination of microdialysis and vapor diffusion allowed successful crystallization. The crystals were of good quality, and useful data were obtained that extended to the nominal resolution of 1.3 A. The space group is P4(3)2(1)2 with cell dimensions of a = b = 42.7 A, c = 103.4 A. More than twenty heavy-atom reagents were screened with the isomorphous replacement technique, and only the mersalyl derivative could be used for the phase determination. The single isomorphous replacement method combined with the anomalous scattering effect of the Hg-atom in mersalyl and the Fe-atom of the heme group was used for the phase determination.

Crystallization↗

Vasoactive intestinal polypeptide provokes acetylcholine release from the myenteric plexus.

Effects of vasoactive intestinal polypeptide (VIP) on the release of acetylcholine (ACh) from longitudinal muscle strips with myenteric plexus (LM) preparations were examined in the guinea pig small intestine. VIP (10(-10) to 10(-6) M) induced a concentration-dependent contraction of LM preparation. The VIP-induced contractions seem to be related to three components, the scopolamine-sensitive, the scopolamine-insensitive, the tetrodotoxin-sensitive, and the tetrodotoxin-insensitive contractions. VIP (10(-10) to 10(-6) M) induced a concentration-dependent increase in the release of [3H]ACh from LM preparations preloaded with [3H]choline. The VIP-evoked [3H]ACh release was inhibited by removal of Ca2+ from the perfusion medium and by treatment with tetrodotoxin but not by scopolamine and hexamethonium. The spontaneous and VIP-evoked [3H]ACh release was not affected by phentolamine, propranolol, methysergide, diphenhydramine, cimetidine, bicuculline, or [D-Pro2, D-Trp7,9]substance P. The result demonstrates that VIP induces contractions of longitudinal smooth muscle directly and indirectly by the stimulation of both cholinergic neurons and noncholinergic excitatory neurons.

Acetylcholine↗