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Biomedical subjects

K Yamasaki

Publications and source records attributed to K Yamasaki.

At least 19 recordsLinked to original sources

A potent and specific agonist, Suc-[Glu9,Ala11,15]-endothelin-1(8-21), IRL 1620, for the ETB receptor.

A series of C-terminal linear peptides of endothelin (ET)-1 and their N alpha-succinyl (Suc) analogs were synthesized and their binding affinities for the two subtypes of ET receptor, ETA and ETB, in porcine lung membranes were examined. Among the synthetic analogs, Suc-[Glu9,Ala11,15]-ET-1(8-21), IRL 1620, was the most potent and specific ligand for the ETB receptor (KiETA/KiETB approximately equal to 120,000) as judged by the Ki values for ETA (1.9 microM) and ETB (16 pM) receptors. IRL 1620 was 60 times more selective for the ETB receptor than ET-3 (KiETA/KiETB approximately equal to 1,900). IRL 1620 (10(-9)-10(-7) M) induced contractions of the guinea pig trachea with a comparable potency to those of ET-1 or ET-3, suggesting that IRL 1620 is a potent ETB receptor agonist.

Amino Acid Sequence

Antiulcer mechanism of action of rebamipide, a novel antiulcer compound, on diethyldithiocarbamate-induced antral gastric ulcers in rats.

The mechanism of the inhibitory action of rebamipide, a new mucosal protective drug, was studied using rats with diethyldithiocarbamate-induced gastric antral ulcers. Rebamipide reduced ulcer formation and inhibited the elevation in lipid peroxide concentration in the gastric mucosa. Rebamipide inhibited both luminol- and lucigenin-dependent chemiluminescence of neutrophils activated by formyl-methionyl-leucyl-phenylalanine. Rebamipide did not alter the reduction of cytochrome c induced by the xanthine-xanthine oxidase system or the NADPH-dependent microsomal lipid peroxidation in the liver. These findings suggest that rebamipide prevents diethyldithiocarbamate-induced gastric ulcer formation by inhibiting neutrophil activation.

Alanine

Spin-echo M-mode NMR imaging.

A nuclear magnetic resonance (NMR) imaging and display method for the observation of the continuous motion of objects is presented. By modifying a line scan technique, the spin-density distribution along a line is displayed in succession. Although spatial information is limited to only one dimension, the motion of the object is recorded at intervals of 55 ms by using a commercially available NMR imaging system. In a phantom study, this method yielded accurate velocity measurements along a single axis. When the method was applied to the human chest, an image analogous to that of M-mode echocardiography was obtained. This method, which can be called spin-echo M-mode NMR imaging, approaches the functional analysis of cardiac wall motion in regions where echocardiography is not possible. The effects of respiratory motion on the left ventricular wall were recorded in addition to its intrinsic contractile motion in an image obtained along a line parallel to the cranio-caudal axis of the body. The advantages of this method to assess cardiac wall motion in a patient with an arrhythmia were also demonstrated.

Atrial Fibrillation

Guanine-nucleotide binding activity, interaction with GTPase-activating protein and solution conformation of the human c-Ha-Ras protein catalytic domain are retained upon deletion of C-terminal 18 amino acid residues.

A truncated human c-Ha-Ras protein that lacks the C-terminal 18 amino acid residues and the truncated Ras protein with the amino acid substitution Gly-->Val in position 12 were prepared by an E. coli overexpression system. The truncated Ras protein showed the same guanine-nucleotide binding activity and GTPase activity as those of the full-length Ras protein. Further, the same extent of GTPase activity enhancement due to GTPase-activating protein was observed for the truncated and full-length Ras proteins. In fact, two-dimensional proton NMR analyses indicated that the tertiary structure of the truncated Ras protein (GDP-bound or GMPPNP-bound) was nearly the same as that of the corresponding catalytic domain of the full-length Ras protein. Moreover, a conformational change around the effector region upon GDP-->GMPPNP exchange occurred in the same manner for both proteins. These observations indicate that the C-terminal flanking region (18 amino acid residues) of the Ras protein does not appreciably interact with the catalytic domain. Therefore, the truncated Ras protein is suitable for studying the molecular mechanism involved in the GTPase activity and the interaction with the GTPase-activating protein. On the other hand, an active form of the truncated Ras protein, unlike that of the full-length Ras protein, did not induce neurite outgrowth of rat pheochromocytoma PC12 cells. Thus, membrane anchoring of the Ras protein through its C-terminal four residues is not required for the interaction of Ras and GAP, but may be essential for the following binding of the Ras-GAP complex with the putative downstream target.

Animals

A 1H-15N NMR study of human c-Ha-ras protein: biosynthetic incorporation of 15N-labeled amino acids.

A 1H-15N NMR study was performed on the GDP-bound form of a truncated human c-Ha-ras oncogene product (171 amino acid residues). Resonance cross peaks of the backbone amide 1H-15N nuclei of a uniformly 15N-labeled protein were observed with heteronuclear single-quantum coherence spectroscopy (HSQC). In order to resolve overlapping cross peaks, selective 15N-labeling of one or two types of amino acid residues (Ala, Arg, Asx, Glx, Gly, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Tyr and/or Val) was carried out using appropriate E. coli mutant strains. By this procedure, all the backbone 1H-15N cross peaks were classified into amino acid types.

Amino Acids

Oleanane glycosides from Glycyrrhiza yunnanensis roots.

From the roots of Glycyrrhiza yunnanensis, collected in Yunnan, China, six new oleanane-type triterpene glycosides named yunganosides A1, B1, C1, D1, E2 and F2 were isolated together with hypaphorine. The structures of these glycosides were established by spectroscopic and chemical means.

Carbohydrate Sequence

Steroid saponins from Polygonatum kingianum.

Four new steroid saponins, kingianosides A-D, were isolated from the rhizome of Polygonatum kingianum, together with two known steroid saponins. On the basis of chemical and spectral evidence, the structures of kingianosides A-D were established as gentrogenin 3-O-beta-D-glucopyranosyl (1-->4)-beta-D-galactopyranoside, gentrogenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-fucopyranoside, 26-O-beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3 beta, 22-diol 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-galactopyranoside and 26-O-beta-D-glucopyranosyl-22-hydroxy-25(R)-furost-5-en-12-on-3 beta,22-diol 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-fucopyranoside, respectively.

Carbohydrate Sequence

Inhibition of phosphoenzyme formation from phosphate and sarcoplasmic reticulum Ca(2+)-ATPase by vanadate binding to high- or low-affinity site on the enzyme.

In the preceding paper, we suggested that 1 mol Ca(2+)-ATPase of sarcoplasmic reticulum (SR) contains 0.5 ml of high-affinity vanadate binding sites as well as 0.5 ml of low-affinity vanadate binding sites [Yamasaki, K. & Yamamoto, T. (1991) J. Biochem. 110, 915-921]. In the present study, we examined the effects of vanadate binding to the high- and low-affinity sites upon phosphorylation of the enzyme by inorganic phosphate (Pi). When vanadate was added to the reaction medium in which the Ca(2+)-ATPase had been phosphorylated by Pi in the absence of Ca2+, the steady-state level of phosphoenzyme (E2P) decreased due to inhibition of its formation. The decrease of E2P after addition of vanadate exhibited biphasic kinetics consisting of an initial fast decay process followed by a slower first-order decay process. The size of the fast E2P decay, which was estimated by extrapolating the slow phase decay to time 0, varied depending on the vanadate concentration with a dissociation constant of 17 microM, and reached maximum at 50 microM vanadate. The maximum value of the fast E2P decay was almost equal to the initial E2P level. The initial fast decay of E2P was competitively prevented by Pi with a dissociation constant of 7.4 mM, which was very close to Km for the E2P formation under similar conditions. These observations suggested that vanadate inhibits E2P formation by competition with Pi at a phosphorylation site on the Ca(2+)-ATPase. The slow first-order decay of E2P corresponded well to the vanadate binding to the high-affinity site of the Ca(2+)-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Activity size distribution of radon progeny in indoor air: comparison of model to data.

The activity size distributions of radon progeny in indoor air are considered. A general theoretical model is presented and then applied to this experiment where experimental data was obtained in a very large and nearly airtight laboratory for two cases: low particle concentration (Case 1) and high particle concentration (Case 2). The balance equations of aerosol particles, radon, and radon progeny in indoor air are solved numerically. The effects of particle coagulation are noticeable for u = 0.005 ms-1, (u. equals friction velocity) but negligible for u = 0.015 ms-1 as long as we adopt a certain theoretical model of wall deposition. Numerical results agreed rather well with this experimental data. Furthermore, an example calculation was done in the case of a usual living space with a high air-exchange rate.

Air Pollutants, Radioactive

A sensitive enzymatic method (SK-013) for detection and quantification of specific periodontopathogens.

Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola have been found to predominate in periodontal pockets of patients with adult periodontitis. These microorganisms hydrolyze the synthetic peptide N-benzoyl-DL-arginine-2-naphthylamide (BANA). In this study, we developed an enzymatic method, designated SK-013, to detect the existence of these microorganisms in subgingival plaque bacteria. This enzymatic method was based on the observation of the hydrolysis of N-carbobenzoxy-glycyl-glycyl-arginyl-3,5-dibromo-4-hydroxyaniline (N-CBz-Gly-Gly-Arg-DBHA) and made more sensitive by adding an enhancing system. The SK-013 was specifically positive for P. gingivalis, B. forsythus, T. denticola, and some strains of Capnocytophaga species, but was not specific for any of the other bacterial strains tested. This SK-013 system may be valuable for detection and quantification of periodontal disease-associated bacteria in subgingival plaque and thus for diagnosis of periodontal infections.

Bacteroides

Determination of optimum cutoff levels of plasma des-gamma-carboxy prothrombin and serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma using receiver operating characteristic curves.

Optimum cutoff levels for plasma des-gamma-carboxy (abnormal) prothrombin (DCP) and serum alpha-fetoprotein (AFP) were determined by analyzing receiver operating characteristic (ROC) curves to discriminate between hepatocellular carcinoma (HCC) and benign hepatic conditions. Plasma DCP levels in 200 patients with HCC and 197 control patients with benign liver diseases were measured by an enzyme immunoassay with anti-DCP monoclonal antibodies, while serum AFP levels for both groups were measured by radioimmunoassay. From ROC curves and tangential lines with a slope of 1.0, the cutoff levels of DCP and AFP were determined to be 0.11 AU/ml and 150 ng/ml, respectively. Lowered cutoff levels of DCP did not improve the sensitivity, in contrast to the increased sensitivity obtained by lowering the specificity of AFP. The sensitivities and specificities determined in this study were close to the currently used values of 0.1 AU/ml for DCP and 200 ng/ml for AFP, justifying these cutoff levels for the differentiation of benign and malignant liver diseases.

Adolescent

Beta-phenyl-beta-alanine prevents the activation of vagal efferent discharges evoked by baclofen and GABA in rats.

The effects of DL-beta-phenyl-beta-alanine (BPBA) on vagal efferent discharges elicited by gamma-aminobutyric acid (GABA) and baclofen were investigated in rats. When given alone, BPBA (40 mg/kg, i.v.) caused no significant change in vagal nerve response and did not elicit any convulsions. Pretreatment with BPBA (40 mg/kg, i.v.) resulted in 70% and 80% reductions in the vagal efferent discharges induced by GABA (400 mg/kg, i.v.) and baclofen (4 mg/kg, s.c.), respectively. The present results suggest that BPBA may be a novel GABA antagonist with respect to vagal activation mechanisms in the CNS.

Animals

Block of sodium channels by tyramine and its analogue (N-feruloyl tyramine) in frog ventricular myocytes.

Pharmacological effects of tyramine and its analogue, N-feruloyl tyramine (NFT), on sodium and calcium currents in frog ventricular myocytes were examined using the whole-cell voltage-clamp technique. To improve the temporal and spatial control of the membrane potential, sodium currents (INa) were recorded in 45.5 mM [Na+]o at 10 degrees C. Both tyramine and NFT (1-100 microM) induced a concentration-dependent decrease in INa evoked from a holding potential of -80 mV without affecting a change in either the time to peak or the time constant for the falling phase of INa. Similarly the reversal potential for INa remained unchanged at a value close to that predicted from the Nernst equation. The finding that both tyramine and NFT decreased INa when activated maximally, from a holding potential of -120 mV, indicates that the amplitude of INa can be reduced independently of a change in the kinetics of the current. In addition, tyramine (100 microM) shifted the membrane potential for half maximal inactivation (Vh) of the steady-state inactivation (h infinity)-curve from -74 to -84 mV without affecting its slope. In contrast, NFT failed to affect the h infinity-curve. The calcium current (ICa) recorded in the presence of 0.3 microM TTX was not affected by either 100 microM tyramine or NFT. We concluded that tyramine directly blocks Na channel by shifting h infinity-curve and by suppressing maximum Na channel conductance, while NFT suppresses only maximum Na channel conductance.

Animals

[Type A personality and level of aspiration in preschool children: some basic characteristics of aspiration levels and their modifications by introducing risk-taking and competitive situations].

The purpose of this study was to investigate some characteristics of aspiration levels of Type A preschoolers. Twenty-two Type A and twenty-one Type B subjects selected from 245 preschoolers were given three tasks: ball-throwing task 1, ball-throwing task 2, and ringtoss task. After investigating some basic characteristics of aspiration levels in a standard situation (ball-throwing task 1), risk-taking (ball-throwing task 2) and competitive (ringtoss task) situations were introduced in order to study the modifications of aspiration levels. The results indicated that Type A children showed higher aspiration levels than Type B children, but that no differences of changes in aspiration levels by introducing risk-taking and competitive situations were found between the two types. These results were discussed from the view point of formation of Type A characteristics.

Aspirations, Psychological

Therapeutic effects of oral rebamipide and in combination with cimetidine on experimental gastritis in rats.

The present study evaluated the therapeutic effects of rebamipide alone and in combination with cimetidine on experimental gastritis established by the administration of 5 mM sodium taurocholate (TCA) for 6 months in rats. Morphological and biochemical analyses were performed to determine the effects of rebamipide, administered alone or in combination with cimetidine, on chronic, atrophic and erosive gastritis. Rebamipide and cimetidine were administered to rats as a dietary admixture for 4 weeks after withdrawal of TCA. Rebamipide dose-dependently reduced the total length of the erosion, normalized the mucosal thickness and increased the number of parietal and total cells, and tended to reduce interstitial infiltration of inflammatory cells and proliferation of collagenous fibers. Moreover, histochemical and biochemical studies also showed rebamipide to be effective. Rebamipide increased the PAS-positive mucus and normalized the reduced gastric mucosal SOD activity. The therapeutic effect of rebamipide on the experimental gastritis was enhanced by the combined use of cimetidine. These results suggest that rebamipide has a therapeutic effect on chronic atrophic erosive gastritis induced by TCA, and that the mechanism of the therapeutic effect is partially due to the increase in PAS-positive mucus and gastric mucosal SOD activity. Furthermore, the enhanced effect of the combination therapy of rebamipide with cimetidine was considered to be due to the actions of both cimetidine and rebamipide.

Administration, Oral

Effect of rebamipide on mucus secretion by endogenous prostaglandin-independent mechanism in rat gastric mucosa.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2 (1H)-quinolinon-4-yl]-propionic acid, OPC-12759, CAS 11911-87-6), an anti-ulcer agent developed to enhance defensive factors in the gastric mucosa, on gastric mucus secretion was studied by a newly developed biochemical method to measure the gastric mucus glycoprotein content in rats. 1 h after intraperitoneal administration, rebamipide did not produce a significant change in the intramucosal mucus contents (surface mucosal layer and deep mucosal layers of corpus and antral regions) but significantly increased the content of soluble mucus, which recovered from the gastric contents, to about 160% of the control value. Since rebamipide has been shown to increase the biosynthesis of prostaglandins, indometacin was administered to the rats prior to rebamipide administration to examine whether the increase in prostaglandin biosynthesis contributes to the rebamipide-induced increase in gastric mucus secretion. The increase in the soluble mucus was not altered by the pretreatment with indometacin, thus indicating that rebamipide per se has a potential to increase the gastric mucus secretion by a mechanism that is not mediated by the endogenous prostaglandins. The effect of rebamipide on the gastric mucus secretion might contribute to heal and to prevent the recurrence of peptic ulcer diseases as well as to maintain the homeostasis of the gastric mucosa.

Alanine

[Quantitative analysis of sodium fast and slow component in in vivo human brain tissue using MR Na image].

In vivo sodium concentrations in the normal brain tissue and a tumorous tissue were analyzed using MR Na image. The nuclear magnetic resonance enabled us to divide the signal from sodium in the living tissue into 2 parts based on the differences of T2 value. Those are fast component having the T2 value of less than 5 msec and slow component of 15-40 msec. We investigated the effect of macromolecules on T2 value of sodium image using polyvinyl alcohol (PVA) powder. MR Na image was taken with the parameters of TR/TD, 110 ms/1.9 ms (FID image) and TR/TE, 110 ms/20 ms (SE image). Saline solution showed high intensity on both FID image and SE image. Saline solution added PVA (PVA phantom) also showed high intensity on FID image, whereas the signal intensity of PVA phantom in SE image extinguished. To know the relation between the signal intensity and sodium concentration, sodium concentration--signal intensity curve was obtained using phantoms with various sodium concentrations (0.05-1.0%). This curve showed a direct proportion between sodium concentration and signal intensity on Na image. We measured further the sodium concentrations of the human brain tissue. Sodium phantoms were arranged around the heads and the MR Na images of the normal brains from 3 volunteers and a patient with a brain tumor (meningioma) were taken. The sodium concentrations of occipital lobe, basal ganglia and the tumorous tissue were calculated using the sodium concentration--signal intensity curve obtained from the phantoms arranged around the heads.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain

[The correlation between hematopoietic status of the bone marrow and peripheral or marrow reticulocyte classification by using the automated reticulocyte analyzer Sysmex R-3000].

In this study peripheral and marrow reticulocytes were counted by using the automated reticulocyte analyzer Sysmex R-3000 with the quick and accurate function of reticulocyte classification dependent on reticulocyte maturation. The correlation of reticulocyte count of the R-3000 to that of visual reticulocyte counting method was r = 0.926, y = 0.88x + 0.305 and r = 0.933, y = 1.32x + 0.328 for peripheral blood and bone marrow, respectively. The hematopoietic status of the bone marrow was reflected in peripheral reticulocytes better than in leukocytes or platelets. Moreover, at recovery stage from bone marrow suppression after chemotherapy, the ratio of immature type (HFR fraction) in peripheral reticulocytes increased to precede in several days increasing total reticulocytes. The relative reticulocyte counts in bone marrow was about 3 times higher than peripheral blood to be drawn at the same time higher and the patients suffering from megaloblastic anemia, MDS or DIC tended to have a much higher reticulocyte count in bone marrow than in peripheral blood.

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