Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 253 records · Page 14Linked to original sources

PubMed1990

Effect of procaterol on the isolated airway smooth muscle and the release of anaphylactic chemical mediators from the isolated lung fragments.

The effects of an orally active and selective beta 2-stimulant, procaterol (OPC-2009) on the isolated pulmonary smooth muscle and the release of chemical mediators from the passively sensitized lung fragments were studied and compared with those of isoprenaline (isoproterenol) and salbutamol. Procaterol potently relaxed the isolated guinea pig trachea and lung parenchyma in a concentration-dependent fashion. The drug at a similar range of concentrations antagonized the contraction of the isolated guinea pig trachea and lung parenchyma or human bronchus induced by leukotriene (LT) D4. Salbutamol and isoprenaline also showed similar effects to those of procaterol on the above experiments, but the potencies were consistently weaker than that of procaterol. The release of either histamine or LTs from the passively sensitized human lung fragments was markedly and dose-dependently inhibited by both the 5 min and 15 h treatment with procaterol (10(-10)-10(-7) mol/l) before antigen challenge. Isoprenaline and salbutamol in 5 min treatment experiments showed similar potency as and less potency than procaterol, respectively, on the release of these mediators, but the inhibition potencies of these drugs, particularly isoprenaline, were remarkably reduced by 15 h treatment. From these results, procaterol, besides the existing use as a bronchodilator, is expected to be a potentially prophylactic drug for allergic asthma because of the strong inhibition of the anaphylactic mediator release.

Albuterol↗

PubMed1990

[Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man].

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Effects of N-556 on experimental allergy models in rats.

The oral anti-allergic effect of 1,3-bis-(2- ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy)propane dihydrochloride (N-556, KY-556) was investigated. 1) N-556 (10-100 mg/kg, p.o.) inhibited dose-dependently the 48-hr homologous PCA in rats, and the duration of action was longer than that of intravenous DSCG. 2) N-556 (20 and 100 mg/kg once a day for 20 consecutive days, p.o.) tended to inhibit the histamine release from actively sensitized rat lung fragments. 3) N-556 (100 mg/kg, p.o.) showed the prolongation of survival time in the rat systemic anaphylaxis. 4) N-556 (100 mg/kg, p.o.) significantly inhibited the increased airway resistance in experimental asthma in rats. These results suggest that N-556 is a promising and orally-active pro-drug of disodium cromoglycate (DSCG) against allergic diseases.

Animals↗

PubMed1990

[A study for non-asbestos casting liners. An experimental study of the adaptability of MOD casting to die].

Asbestos liners for investment metal casting has frequently been used in dental laboratory work. In recent years, the dangerous properties of asbestos to the human body were reported in Europe and the United States, and casting liners without asbestos were developed and marketed by many manufacturers. These are so-called non-asbestos liners. This study evaluated the adaptability of MOD inlay castings to dies using 8 kinds of commercial non-asbestos liners of ADA standard No. 2 specifications. The results were as follows; Single and double layers of Casting ribbon, New Asbestos Ribon, Shofu experimental, and KAOLIN showed good adaptation. Shofu experimental with a single layer showed the best marginal adaptation (10 microns). OVAL LINERS and CASTING LINERS with single layer showed good adaptation, but with double layers the adaptation was poor. In FLASK LINER, the double layer showed better adaptation than that with a single layer. Most non-asbestos liners used in this study are adequate in useful to MOD inlay castings.

Asbestos↗

PubMed1990

[A benzodiazepine antagonist flumazenil in clinical use--a dose finding study].

The effective dose, usefulness and side effects of flumazenil, a specific benzodiazepine antagonist, have been investigated in 72 sleeping patients after the end of the surgical operation who had received flunitrazepam 0.03 mg.kg-1, a long acting benzodiazepine. The patients received intravenous injections of flumazenil 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg per person as initial doses. Four minutes after the injection of flumazenil, the percentages of the patients who were awake, were 47.4% in 0.1 mg group, 82.4% in 0.2 mg group, 82.4% in 0.4 mg group and 88.2% in 0.8 mg group respectively. There were several side effects observed in all the groups except 0.2 mg group. However, they presented no clinical problems. Therefore, flumazenil 0.2 mg as the initial dose, is considered appropriate.

Adolescent↗

PubMed1990

Protease-activated form of protein kinase C with Mr 80,000 generated from rat liver plasma membrane by trypsin-like protease.

New type of protease-activated form of protein kinase C was generated from rat liver plasma membrane by action of endogenous trypsin-like protease. The molecular mass was estimated to be about 80,000 by immunoblot analysis which was slightly smaller (approximately 2,000) than that of native protein kinase C. The protein kinase activity was 2-times stimulated by Ca2+ and phospholipid and inhibited by the synthetic peptide derived from the pseudosubstrate region of protein kinase C. This type of activated kinase was produced in purified enzyme system in the absence of either Ca2+ or phospholipid or both. These results suggest that limited proteolysis generating the active form of Mr 80,000 may occur on the inactive form of protein kinase C.

Amino Acid Sequence↗

PubMed1989

Phospholipids differently modulate the activity of cytosolic protein-tyrosine kinase from porcine spleen.

Effect of membrane phospholipids on the activity of cytosolic protein-tyrosine kinase from porcine spleen (CPTK-40) has been studied. Using poly(Glu Na, Tyr)4:1 as a substrate, phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine had stimulatory effects on that phosphorylation activity, however phosphatidic acid had inhibitory and phosphatidylinositol had no effects. Similar results were obtained using[Val5]angiotensin II as a substrate. On the other hand using basic protein (H2B histone and myelin basic protein) as substrates, phosphatidic acid stimulated the activity of CPTK-40, while phosphatidylinositol inhibited the activity. Phosphatidylethanolamine, phosphatidylcholine and phosphatidylserine caused different effect on the activity of CPTK-40 depending on the substrate employed. However using acidic protein (tubulin and casein) as substrates, the activity of CPTK-40 was neither stimulated nor inhibited by any phospholipids. These results suggest that phospholipids may modulate the activity of CPTK-40.

Animals↗

PubMed1989

Phosphorylation of smg p21, a ras p21-like GTP-binding protein, by cyclic AMP-dependent protein kinase in a cell-free system and in response to prostaglandin E1 in intact human platelets.

We have separated multiple small Mr GTP-binding proteins (G proteins) from bovine brain membranes by several column chromatographies and purified to near homogeneity four of them, including a novel Mr 24,000 G protein (smg p25A), a novel Mr 22,000 G protein (smg p21), the rho protein (rho p20), and the c-Ki-ras protein (c-Ki-ras p21). Among these small Mr G proteins, only smg p21 is phosphorylated stoichiometrically by cAMP-dependent protein kinase (protein kinase A), and c-Ki-ras p21 is phosphorylated to a small extent by protein kinase A in a cell-free system. None of smg p25A, rho p20, and other partially purified small Mr G proteins is phosphorylated by protein kinase A. Neither smg p21 nor other small Mr G proteins are phosphorylated by protein kinase C. About 1 mol of phosphate is maximally incorporated into 1 mol of smg p21 by protein kinase A. Only serine residue(s) are phosphorylated. The guanosine 5'-3-O-(thio) triphosphate (GTP gamma S)-bound and GDP-bound forms of smg p21 are phosphorylated with the same reaction velocity. The phosphorylation of smg p21 affects neither its GTP gamma S-binding nor GTPase activity. smg p21 is found in human platelets, and this human platelet smg p21 is also phosphorylated by protein kinase A at the same site(s) as bovine brain smg p21 in a cell-free system. When intact human platelets are stimulated by prostaglandin E1 known to elevate the cAMP level, four proteins with apparent Mr values of 240,000, 50,000, 24,000, and 22,000 are phosphorylated. These four proteins are also phosphorylated by the action of dibutyryl cAMP but not by the action of thrombin, Ca2+ ionophore A23187, or 12-O-tetradecanoylphorbol-13-acetate. Among the four proteins, the Mr 22,000 protein is identified as smg p21. The site(s) of phosphorylation of smg p21 by protein kinase A in a cell-free system are identical to that phosphorylated in response to prostaglandin E1 in intact platelets. These results indicate that among many small Mr G proteins, smg p21 is selectively phosphorylated by protein kinase A and that this G protein is also phosphorylated by this protein kinase in response to prostaglandin E1 in intact human platelets.

Alprostadil↗

PubMed1989

Mechanism of membrane damage induced by the amphipathic peptides gramicidin S and melittin.

The action of gramicidin S and melittin on human erythrocytes, Staphylococcus aureus and Escherichia coli was studied as an extension of the previous study (Katsu, T., Ninomiya, C., Kuroko, M., Kobayashi, H., Hirota, T. and Fujita, Y. (1988) Biochim. Biophys. Acta 939, 57-63). These amphipathic peptides stimulated the release of membrane phospholipids outside cells in a concentration range causing permeability change. The shape change of erythrocytes from normal discoid to spiculate form was observed just prior to the release of membrane components. We have proposed the following action mechanism of gramicidin S and melittin. The peptide molecules were predominantly accumulated in the outer half of the bilayer, deforming the erythrocyte cell into crenature. A large accumulation made the membrane structure unstable, resulting in the release of membrane fragments and the simultaneous enhancement of permeability. The action mechanism of these peptides was compared with that of simple surfactants.

Bee Venoms↗

PubMed1989

Purkinje cell abnormalities and synaptogenesis in genetically jaundiced rats (Gunn rats).

The course of cytological abnormalities and synaptogenesis of Purkinje cells were investigated in the culmen of cerebella from homozygous Gunn rats with hereditary hyperbilirubinemia from postnatal day 7 to adulthood (5-10 months old). The affected Purkinje cells were abundant at day 7. A large number of Purkinje cells reached the fully advanced stage of degeneration during the ensuring 16 days and disappeared between days 12 and 30. The Purkinje cells remaining at day 30 were less affected and recovered by the adult stage. Various abnormalities in Purkinje cell synaptogenesis with the parallel fibers, climbing fibers, and basket and stellate cell axons were observed. Primitive junctions between parallel fibers and Purkinje dendritic shafts were often found in adulthood. The parallel fiber boutons lacking postsynaptic partners and facing astrocytic processes were often noted from day 18 to adulthood. The persistence of such presynaptic elements suggests some mechanisms for stabilizing the synaptic elements once they have been formed. Many of the parallel fiber synaptic boutons with or without their postsynaptic partners were enlarged and were assumed to be transsynaptically affected by Purkinje cell damage. A number of climbing fiber synapses with perisomatic process of Purkinje cells, which are transient in normal synaptogenesis, were present at day 30 and a few of them were still found even in adulthood. Basket and stellate cell synapses were often found in abundance on the remaining Purkinje cells in adulthood, though they were not frequently encountered during the development period.

Aging↗

PubMed1989

Thrombin and collagen induce rapid phosphorylation of a common set of cellular proteins on tyrosine in human platelets.

The ability of thrombin and collagen to induce protein-tyrosine phosphorylation in intact human platelets was assessed by using antibodies to phosphotyrosine in conjugation with immunoblots. Upon stimulation by thrombin there was an increase in the amount of protein-tyrosine phosphorylation of three bands with molecular masses of 135, 124, and 76 kDa in a time-dependent manner. The tyrosine phosphorylation in these three proteins increased in a concurrent fashion and reached a maximum level in 10 s and then a plateau or a slight decrease. Stimulation by collagen was also followed by an increase in tyrosine phosphorylation of 135- and 124-kDa proteins. Unlike stimulation by thrombin, collagen induced no obvious tyrosine phosphorylation of 76-kDa protein. The time courses for thrombin- or collagen-induced protein-tyrosine phosphorylation were similar to that for [14C] serotonin release. These results suggest that 135- and 124-kDa proteins are a common set of proteins that become phosphorylated on tyrosine residue during platelet activation.

Antibodies, Monoclonal↗

PubMed1989

Ionic strength-dependent interaction of rat liver casein kinase I with plasma membrane.

Casein kinase I binding to rat liver plasma membrane was rapidly released from membrane by increasing the ionic strength above physiological level. The released activities at 250-300 mM NaCl were 3-4-fold higher than those obtained under lower ionic strength below 100 mM NaCl. This reaction occurred nonenzymatically and was reversible. By lowering the ionic strength from 250 mM to 50 mM NaCl by dilution at least 50% of the released enzyme was rebound to plasma membrane. By gel filtration analysis, most of the released enzyme activity under higher NaCl concentration was recovered around the molecular mass of 35,000 which corresponded to that of casein kinase I. This enzyme showed the tendency to aggregate under lower ionic strength (50 mM NaCl), but existed as monomer under higher ionic strength (250 mM NaCl). These results suggest that the release of casein kinase I from plasma membrane and the rebinding to membrane induced by the alteration of ionic strength seem to be an important regulatory mechanism in determining the subcellular distribution of this enzyme.

Animals↗

PubMed1989

Effect of poly-basic amino acids on the phosphorylation of various substrate proteins by cytosolic protein-tyrosine kinase from porcine spleen.

Cytosolic protein-tyrosine kinase from porcine spleen (CPTK-40) is strongly activated by poly-L-lysine using bovine serum albumin, ovalbumin, phosphorylase b, calmodulin and H1 histone as substrate proteins. However, this polyamine inhibited the enzyme activities when myelin basic protein, tubulin and H2B histone were used as substrate proteins. These stimulatory and inhibitory effects on CPTK-40 are not specific for polylysine, but polyarginine and polyornithine have similar effects on this phosphorylation reaction. Effect of poly-basic amino acids on CPTK-40 seems to be mainly on the substrate proteins, rather than on the enzyme itself.

Animals↗

PubMed1989

Orientation of bone mineral and its role in the anisotropic mechanical properties of bone--transverse anisotropy.

An orientation of hydroxyapatite (HAP) crystals in bovine femur mineral was investigated by means of X-ray pole figure analysis (XPFA). It was found that the c-axis of HAP generally orients parallel to the longitudinal axis of bone (bone axis) and a significant amount of c-axis was oriented in other directions, in particular, perpendicular to the bone axis. Comparing these results with those of the small angle X-ray scattering (SAXS) investigation by Matsushima et al. (Jap. J. appl. Phys. 21, 186-189, 1982) at least two types of morphology of bone mineral were found; rod like bone mineral having the c-axis of HAP crystal parallel to the longitudinal axis of the rod and that having the c-axis not parallel, in a particular case, perpendicular to its longitudinal axis. Transverse anisotropy in mechanical properties of bone was reproduced by the estimation of Young's moduli by using the structural results mainly from XPFA. It is concluded that the anisotropy in mechanical properties of bone is well explained by taking account of the non-longitudinal (off-bone) axial distribution of orientation of bone mineral.

Animals↗

PubMed1989

Protective effect of oral cysteamine against induction of gastric cancer by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of oral administration of cysteamine (2-aminoethanethiol hydrochloride) on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was investigated in inbred Wistar rats. Oral administration of 0.4% cysteamine in food after treatment with MNNG for 25 weeks significantly reduced the incidence and number of adenocarcinomas of the glandular stomach in experimental Week 52. Histological examination showed that adenocarcinomas that did develop in rats fed on cysteamine had high mucin-producing activity. Furthermore, oral administration of cysteamine caused a significant increase in serum gastrin level and significant decreases in the antral mucosal pH and the labeling indices of the antral mucosa. These findings indicate that cysteamine inhibits the development of gastric adenocarcinomas when given orally. This effect may be related to its ability to decrease proliferation of antral mucosal cells.

Adenocarcinoma↗

PubMed1989

Subchronic feeding studies with nivalenol in C57BL/6 mice.

Groups of ten C57BL/6CrSlc SPF mice of each sex were fed diets containing 0, 6, 12 or 30 ppm nivalenol for 4 or 12 wk. Body-weight gains of males and females were depressed, dose-dependently in the case of males. Feed consumption was also depressed. Treatment-related changes in liver, kidney, spleen and thymus weights were seen in some groups but showed no clear trends. No gross or histopathological lesions were seen in the organs examined but treated groups had considerably less fatty tissue at autopsy than did controls. There was a dose-dependent increase in serum alkaline phosphatase activity. Other serum parameters showed scattered significantly altered value but no clear trends, except for serum GOT values for males fed 12 and 30 ppm for 12 wk; these showed a statistically significant dose-related increase, but were within the normal range and were not considered to indicate hepatotoxicity.

Animals↗

PubMed1989

Chronic toxicity of nivalenol in female mice: a 2-year feeding study with Fusarium nivale Fn 2B-moulded rice.

Groups of 42 7-wk-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12 and 30 ppm nivalenol (NIV) for 2 years. Body-weight gain was reduced in all treated groups of animals and feed efficiency was reduced, significantly so, in the high-dose group. The absolute weights of the liver in the 30-ppm group, and of the kidneys in the 12- and 30-ppm groups were significantly reduced, compared with those of the controls. When expressed relative to brain weight there was a reduction in the kidney weight of the 12-ppm NIV group only. Some leucopenia was seen in the treated mice, particularly in the 30-ppm group, although this was not statistically significant, and there were dose-dependent increases in the serum concentrations of alkaline phosphatase and non-esterified fatty acids. No tumours attributable to NIV were found in any of the experimental groups. Naturally occurring tumours, mostly lymphomas, were of similar incidence in all groups, but developed later and appeared to grow more slowly in the mice of the 30-ppm group than in those of other groups. The incidence of amyloidosis, particularly in the small intestine, was low in the two higher dose groups compared with that in the control group. The mortality rate of the 30-ppm NIV group was lower than that of the control group and this may be partly due to the lower tumour incidence in the earlier period and partly due to the lower incidence of amyloidosis.

Amyloidosis↗

PubMed1989

Further studies on the ionic strength-dependent proteolytic activation of protein kinase C in rat liver plasma membrane by endogenous trypsin-like protease.

cAMP and Ca2(+)-independent histone kinase was generated from rat liver plasma membrane in an ionic strength-dependent manner by the action of an endogenous trypsin-like protease (Hashimoto, E. et al. (1986) FEBS Lett. 200, 63-66). In addition to the effect of ionic strength, this proteolytic activation of protein kinase proceeded faster at alkaline pH. In an attempt to identify the activated kinase as the protease-activated form of protein kinase C (protein kinase M), the active enzyme released from plasma membrane was highly purified and characterized. Various properties including Mg2+ requirement in histone phosphorylation, substrate specificity, effects of protein kinase activators, and inhibitors and comparison of catalytic properties by peptide map analysis were compatible with those of protein kinase M reported earlier. Immunoblot analyses also supported the idea that the protein kinase subjected to proteolytic activation was protein kinase C. The subtype of protein kinase C detected in this study was identified as type III enzyme encoding alpha-type sequence from the elution profile from hydroxyapatite column. These results suggest that type III protein kinase C bound to rat liver plasma membrane has an ability to be activated by endogenous trypsin-like protease dependently on the alteration of ionic strength and pH around the plasma membrane.

Animals↗