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Biomedical subjects

H Miyata

Publications and source records attributed to H Miyata.

At least 307 records · Page 17Linked to original sources

Serum Tamm-Horsfall glycoprotein level in children with various renal diseases.

Serum Tamm-Horsfall glycoprotein (THGP) concentrations were measured by a competitive enzyme-linked immunosorbent assay using peroxidase-labeled THGP in 168 patients, aged 10.5 +/- 4.6 years, with various renal diseases. Using this method, THGP was determined in the concentration range of 10-10(3) micrograms/l. Serum THGP levels ranged from 130 to 350 micrograms/l in 32 control subjects, aged 1-16 years with normal renal function. In most patients with renal disease, the serum THGP levels were lower than those in control subjects. In particular, the serum THGP levels were more reduced according to the decrease in the clearance values of endogenous creatinine (CCR). These findings suggested that the measurement of serum THGP levels is helpful in the evaluation of renal function. On the other hand, 3 patients with vesicoureteric reflux showed higher serum THGP levels than control subjects, though the CCR values in 1 of these patients was lower. These high serum THGP levels may be the result of urinary backflow into circulation.

Adolescent↗

Effect of a novel antiallergic drug, pemirolast, on activation of rat peritoneal mast cells: inhibition of exocytotic response and membrane phospholipid turnover.

The effects of a potent antiallergic drug, pemirolast (TBX), on activation of signal-transducing phospholipase C and A2, were examined in rat peritoneal mast cells. TBX at concentrations between 10(-7) and 10(-5) g/ml effectively inhibited degranulation in response to both antigen and compound 48/80. At the same concentrations the drug markedly suppressed the formation of 1,2-diacylglycerol and phosphatidic acid, and the decrease in phosphatidylinositol, suggesting the prevention of phospholipase C activation. The blockade of phospholipase A2 was suggested by the decrease in agonists-induced arachidonic acid liberation. These results indicate that TBX may exert its inhibitory effects on mast cells, at least in part, by preventing the activation of signal-transducing phospholipases.

Animals↗

A cellular mechanism for impaired posthypoxic relaxation in isolated cardiac myocytes. Altered myofilament relaxation kinetics at reoxygenation.

Single, isolated rat ventricular myocytes were made hypoxic for 10 minutes and then reoxygenated. During hypoxia, there was a marked abbreviation of the mechanical twitch, without a decrease in its amplitude. Immediately after reoxygenation, both the time to peak shortening and the duration of relaxation were markedly prolonged, and they remained prolonged for 10-50 minutes. The alterations in contraction and relaxation were not associated with any change in the time course of either the transmembrane action potential or the cytosolic calcium transient, as recorded with the fluorescent probe indo 1. Intracellular pH, measured with a fluorescent probe (carboxyseminaphthorhodofluor), showed an acid shift during hypoxia and an alkaline rebound immediately after reoxygenation. The time courses of intracellular pH and contraction duration were not parallel during hypoxia or reoxygenation, and simulation of the alkaline pH shift by lowering PCO2 or superfusing NH4Cl (in the absence of exposure to hypoxia) did not quantitatively reproduce the prolongation of relaxation seen after reoxygenation. The prolongation of contraction after reoxygenation could be overridden by the beta-adrenergic agonist isoproterenol or the nonenzymatic phosphatase butanedione monoxime. We conclude that delayed relaxation after reoxygenation exists at the single cell level and is due to an alteration of the properties of the myofilaments. Intracellular pH is not the primary mediator of this alteration. We speculate that alteration of intracellular inorganic phosphate or covalent modification of the myofilaments might be involved.

Actin Cytoskeleton↗

[Effects of cholinergic drugs on delayed discrimination disruption by AF64A in rats].

In a 2-lever operant chamber situation for food reinforcement, the effects of nicotine, arecoline and physostigmine on delayed discrimination responses in rats treated with ethylcholine mustard aziridinium ion (AF64A) were investigated. AF64A at 6 nmol, i.c.v., decreased the percentage of correct choices (% CR) at the delay time of 4 sec, and this effect depended on the delay time. On the other hand, AF64A at the same dose shortened the latency (LAT: the period from the end of the delay time to the initiation of lever-pressing responses) at the delay time of 16 sec, but this effect didn't depend on the delay time. Nicotine at 0.25 mg/kg, s.c., improved the decrease of % CR; and at 0.13-0.5 mg/kg, s.c., it shortened LAT at the delay time of 4 sec in rats treated with AF64A. Arecoline at 4 mg/kg, s.c., and physostigmine at 0.06-0.5 mg/kg, s.c., extended LAT, but both drugs showed no effects on % CR at the delay time of 4 sec in rats treated with AF64A. These results suggest that the present procedure might be useful for the evaluation of drug effects on memory in rats, and nicotine improved the delayed discrimination disruption induced by AF64A.

Animals↗

[Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models].

Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed. Neither gabexate mesilate (FOY, 10 mg/kg/hr) nor nafamostat mesilate (FUT, 0.1 mg/kg/hr) improved endotoxin-induced DIC. FR-860 showed comparable potency to UF-heparin in plasma anti-factor Xa (F.Xa) activity. However, FR-860 was weaker than UF-heparin in prolongation of activated partial thromboplastin time. In the thrombin-induced DIC model, both FR-860 and UF-heparin significantly improved, as seen in the endotoxin-induced DIC model, the changes in coagulation and fibrinolytic parameters and suppressed the production of pulmonary thrombus. On the other hand, both FOY and FUT showed significant but weak improvement in this model. In addition, FR-860 inhibited the enhancement of fibrinolysis and the production of pulmonary thrombus in the lactic acid-induced DIC model. These results suggest that the efficacy of FR-860 on DIC in rats is comparable to that of UF-heparin and that the efficacy can be attributed to its anti-F.Xa activity. FR-860 can be expected to be a useful therapeutic drug for DIC.

Animals↗

[Studies on the involvement of the nucleus accumbens in the discriminative effects of nicotine in rats].

The central mechanism mediating the discriminative effects of nicotine was studied using rats. Rats were trained to discriminate subcutaneously administered nicotine at 0.5 mg/kg from saline in a 2-lever operant chamber situation for food reinforcement. 1) Nicotine administered into the lateral ventricle at both 100 micrograms and 120 micrograms substituted for subcutaneously administered nicotine at 0.5 mg/kg. This result indicates that the discriminative effects of nicotine are mediated centrally. 2) Among the drugs, acetylcholine at 0.5-10 micrograms administered into the lateral ventricle and methamphetamine at 5-40 micrograms and dopamine at 1-10 micrograms administered into the nucleus accumbens, none substituted for subcutaneously administered nicotine. These results indicate that the discriminative effects of nicotine differ from those of the above drugs. 3) Nicotine at 100 micrograms administered into the nucleus accumbens almost completely substituted for subcutaneously administered nicotine. In addition, mecamylamine at 180 micrograms administered into the nucleus accumbens attenuated the discriminative effects of subcutaneously administered nicotine. These results suggest that nicotinic receptors in the nucleus accumbens may be involved in the discriminative effects of nicotine. However, further studies are needed, since the nucleus accumbens is regarded not to be a major site of action of nicotine for these effects because of its low susceptibility to nicotine and mecamylamine.

Acetylcholine↗

Carbohydrate histochemistry of bovine duodenal glands.

The complex carbohydrates in the bovine duodenal glands were examined histochemically using 5 peroxidase-labeled lectins to achieve a better knowledge of their glycoprotein profiles. The presence of at least 2 different cell types and secretion of neutral mucin were observed in the bovine duodenal glands. The duodenal gland cells located in the central area of the lobules contained neutral glycoproteins with different saccharide residues as beta-D-gal-(1-3)-D-galNAc, alpha-D-galNAc, beta-(1-4)-D-glcNAc, NeuNAc and D-galNAc. The other cell types located in the peripheral area of the lobules contained alpha-L-Fuc, alpha-D-galNAc, beta-(1-4)-D-glcNAc, NeuNAc and D-galNAc. These findings seemed to be characteristic of a unique digestive process of the ruminant.

Animals↗

WGA-HRP studies on the fiber connections from the spinal cord to the Deiters' nucleus.

The labyrinthine-spinal reflexes are influenced by the inputs from the cervical and lumbal propriocepters. We studied the afferent route by the retrograde WGA-HRP method in cats. After the injection of WGA-HRP into either the dorsal or the ventral Deiters' nucleus, labeled neurons were investigated in the spinal cord, the cerebellum, the contralateral vestibular nucleus complex and the brain stem nucleus. In this paper, we report the results in the spinal cord of cats. i) When WGA-HRP was injected into the dorsal Deiters' nucleus, labeled neurons in the spinal cord were found mainly extending from the cervical to the lumbosacral area of the spinal cord. A number of labeled cells were located predominantly in the contralateral cervical segments, while a small number of labeled cells was found ipsilaterally in the lumbosacral segments. ii) In the case of the ventral Deiters' nucleus, labeled neurons were found extending from the cervical to the upper thoracic area of the spinal cord. Localization of labeled neurons in the spinal cord was limited mainly to Rexed's laminae VII and VIII. These results suggest that the afferent fibers from the spinal cord to the Deiters' nucleus are closely related to the labyrinthine-spinal reflex.

Afferent Pathways↗

Studies on vestibulo-spinal reflexes by examination of labyrinthine-evoked EMGs of lower limbs.

Evoked electromyograms (EMGs) induced by galvanic stimulation of the labyrinth were examined in the muscles of the lower limbs. The labyrinthine-evoked EMGs appeared in the muscles of the femoral and gluteal regions and of the legs, and these muscle activities were changed by the head position in spite of the labyrinthine stimulation being the same. The vestibulo-spinal reflexes fulfil these functions in coordination with the neck proprioceptor.

Ear, Inner↗

The vestibulo-autonomic function viewed from cardiac responses in centrifuged monkeys.

Vestibulo-autonomic function was examined as the change of cardiac parameters (HR and SV) to +Gz and -Gx accelerations for 1,000 s in intact and bilaterally labyrinthectomized monkeys. Under anesthetized conditions, HR and SV slightly changed to +2Gz acceleration in both monkeys. In +3Gz acceleration, changes were remarkable and significant. HR increased in intact monkeys by as much as 30% while it decreased in labyrinthectomized monkeys, although a moderate initial increase was observed. SV decreased in intact as well as labyrinthectomized monkeys, but the reduction was significant and larger for the latter. This implies that vestibular input could modulate autonomic function. For larger +Gz, both intact and labyrinthectomized monkeys could tolerate no more due to severe cardiac dysfunction (rapid HR and SV decrease) which appeared soon after +4Gz application. In case of -Gx application, HR increased, although slightly, in proportion to the amplitude of applied -Gx in both monkeys, with less changes in labyrinthectomized ones. SV hardly changed in smaller -Gx, while it increased in larger -Gx. Difference between intact and labyrinthectomized monkeys was observed in -6Gx and -8Gx conditions.

Acceleration↗

The role of free radicals in myocardial cell injury.

Free radicals can affect lipids of membranes by initiating peroxidation. Since alterations in membrane fluidity can modulate membrane functions including ion permeability, the effects of free radicals on the intracellular Ca2+ level ([Ca2+]i) and membrane fluidity were studied. Human erythrocytes were spin-labeled with 5-DSA and the membrane fluidity was quantified by ESR during application of oxygen-derived free radicals. The morphology was observed by the scanning electron microscopy. The effects of H2O2 on [Ca2+]i were studied using single guinea pig ventricular myocytes and fura-2 AM. Superoxide and H2O2 (10(-3) and 10(-4) M) induced a decrease in membrane fluidity and morphological changes of erythrocytes. [Ca2+]i significantly increased from the control value (53 +/- 4 nmol/litre) to 110 +/- 29 nmol/litre when the cells were shortened, and to 130 +/- 26 nmol/litre before cells became rounded. This study showed that [Ca2+]i was significantly increased by oxygen-derived free radicals, possibly by lipid peroxidation of the cell membrane. During perfusion with H2O2 however, the increase in [Ca2+]i was not pronounced. Therefore, we suspect that the mechanism of cell injury due to free radicals may be a combination of direct cell membrane injury and Ca2+ overload rather than intracellular Ca2+ overload.

Animals↗

Heterogeneity in cellular response and intracellular distribution of Ca2+ concentration during and after metabolic inhibition.

STUDY OBJECTIVE: To characterise cell injury during myocardial hypoxia and reoxygenation, [Ca2+]i was measured in guinea pig ventricular myocytes using digital images of fura-2 fluorescence. DESIGN: [Ca2+]i and cell morphology were measured during and after the perfusion of 2 mmol.litre-1 sodium cyanide (NaCN). EXPERIMENTAL MATERIAL: 28 ventricular myocytes isolated from guinea pig hearts. MEASUREMENTS AND MAIN RESULTS: Eight out of 28 cells became rounded during the perfusion with NaCN, and [Ca2+]i increased from 48 (SEM 6) nmol-litre-1 to 163(24) (p less than 0.01) before cell rounding, and to 311(46) (p less than 0.01) after cell rounding. Ten cells were rounded after the washout of NaCN, and [Ca2+]i increased to 252(41) nmol.litre-1 before cell rounding (p less than 0.01), and to 314(48) after cell rounding (p less than 0.01). Intracellular distribution of [Ca2+]i was heterogeneous in some cells with high [Ca2+]i. The values of [Ca2+]i before and after cell rounding, during and after the perfusion of NaCN, were significantly lower than those during the perfusion of strophanthidin (0.1 mmol.litre-1). CONCLUSIONS: There appeared to be a mixed population of myocytes, some showing normal [Ca2+]i and shape, and others showing high [Ca2+]i and contracture, during the perfusion or the washout of NaCN. Ca2+ overload alone is unlikely to be the main and the only mechanism of cell injury during myocardial hypoxia/reoxygenation. Other mechanisms such as membrane disturbance could be involved.

Animals↗