Search PubMed⌕ Search

Biomedical subjects

T Ono

Publications and source records attributed to T Ono.

At least 775 records · Page 43Linked to original sources

Protein kinase C-independent sensitization of contractile proteins to Ca2+ in alpha-toxin-permeabilized smooth muscle cells from the guinea-pig stomach.

Involvement of protein kinase C in receptor-operated Ca2+ sensitization of cell shortening was investigated by use of alpha-toxin-permeabilized smooth muscle cells from the fundus of the guinea-pig. Most of the isolated cells responded to 0.6 microM Ca2+ with a maximal shortening to approximately 65% of the resting cell length. Addition of acetylcholine (ACh) at a maximal concentration (10 microM) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 microM to 0.2 microM. The augmentation of Ca2+ sensitivity by ACh was not inhibited by specific protein kinase C inhibitors, calphostin C and K-252b at a concentration of 1 microM. These findings suggest that protein kinase C is not involved in the muscarinic receptor-operated augmentation of Ca2+ sensitivity.

Acetylcholine↗

Receptor-coupled shortening of alpha-toxin-permeabilized single smooth muscle cells from the guinea-pig stomach.

1. Isolated single smooth muscle cells from the fundus of the guinea-pig stomach were permeabilized by use of Staphylococcus aureus alpha-toxin. Receptor-coupled shortening of individual cells was monitored under phase contrast microscopy. 2. Most of the isolated cells responded to 0.6 microM Ca2+, but not to 0.3 microM Ca2+, with a resulting maximal shortening to approximately 65% of the resting cell length. The contractile activity of these permeabilized cells lasted for several hours and repeated shortening was readily achieved after washing out. 3. Addition of acetylcholine (ACh) at a maximal concentration (10 microM) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 microM to 0.2 microM, and 1 mM guanosine 5'-diphosphate (GDP) blocked this decrease. Moreover, treatment with 100 microM guanosine 5'-triphosphate (GTP) mimicked the action of ACh. 4. Addition of 100 microM inositol 1,4,5-trisphosphate (InsP3) with 0.2 microM Ca2+ did not cause cell shortening, whereas 10 microM ACh with 0.2 microM Ca2+ did, suggesting that InsP3-induced Ca2+ release is not involved in ACh-operated cell shortening. 5. The present study demonstrates an alpha-toxin-permeabilized single smooth muscle cell preparation which retains its receptor function and also provides an insight into mechanisms leading to augmentation of Ca2+ sensitivity by stimulation of muscarinic receptors or GTP-binding proteins.

Acetylcholine↗

Paraventricular neuron chemosensitivity and activity related to blood pressure control in emotional behavior.

1. Unit activity in the paraventricular nucleus (PVN) and blood pressure (BP) of the rat were recorded during discrimination learning of cue tone (CTS+) predicting reward [glucose and intracranial self stimulation (ICSS)], and cue tone (CTS-) predicting aversion (electric shock or tail pinch). Adrenergic systems in the PVN were investigated by electrophoretic application of norepinephrine (NE), and by electrophoretic application or direct microinjection of its antagonists (prazosin, yohimbine, and propranolol). 2. Of 65 PVN neurons analyzed, 35 responded during CTS learning in one or more phases of an operant task. Of these, activity of 20 neurons was increased nondiscriminatively by CTS+ and CTS-, and reward and aversion. In parallel with these neuronal activity increases, BP (systolic, diastolic, and mean) was also increased by both CTS+ and CTS- (10-35 mmHg), and reward and aversion (20-47 mmHg). Both neuronal activity and BP increases during CTS learning were suppressed during extinction. 3. Paraventricular neurons, the activity of which correlated with BP increase during CTS learning, were excited by electrophoretic application of NE and Na+ and fired phasically during inter-trial intervals. Activity increases of these neurons during CTS learning, which was related to BP increase, were blocked by electrophoretically applied prazosin (alpha 1-antagonist), but not by yohimbine (alpha 2-antagonist) or propranolol (beta-antagonist). 4. Direct microinjection of prazosin into the PVN suppressed BP increase during CTS learning. Operant licking for reward was not suppressed by prazosin injection. Microinjection of yohimbine or propranolol into the PVN did not suppress either BP increase during CTS learning or operant licking to obtain reward. 5. These results suggest that afferent alpha 1-adrenergic input to the PVN is important to the central BP control during CTS learning in emotional behavior.

Acoustic Stimulation↗

Catecholamine and acetylcholine sensitivity of rat lateral hypothalamic neurons related to learning.

1. Unit activity in the rat lateral hypothalamus (LHA) was recorded during discrimination learning of cue tone (CTS) or cue light (CL) stimulation that predicted reward by glucose or intracranial self stimulation (ICSS), or aversion by weak electric shock or tail pinch. Roles of the catecholaminergic and cholinergic systems in the LHA were investigated by electrophoretic application of dopamine (DA), norepinephrine (NE), acetylcholine (ACh), and their antagonists [spiperone (SPP), phenoxybenzamine (PBZ), phentolamine, propranolol, and atropine (Atr)]. 2. Activity of 264 LHA neurons was recorded. Of these, 234 (89%) responded during CTS learning in one or more phases. Of 121 neurons tested by both rewarding and aversive stimuli, 86 (71%) discriminated reward and aversion and their respective CTSs. 3. Effects of DA on 138, NE on 134, and ACh on 73 neurons were tested. Among these, 67 were tested with all three. DA inhibited 40 and excited 14. NE inhibited 74 and excited 10. ACh excited 35 and inhibited 3. DA-sensitive neurons responded to both NE (P less than 0.001) and ACh (P less than 0.05) more often than DA-insensitive neurons. In most cases, the effect of DA was similar to the effect of NE, and opposite to the effect of ACh. The inhibitory effect of DA was blocked by SPP, a D2 antagonist, and the excitatory effect of ACh was blocked by Atr. The inhibitory effect of NE was blocked by the beta-antagonist, propranolol, and enhanced by the alpha-antagonist, phentolamine. 4. DA-sensitive neurons responded to both rewarding and aversive stimuli and respective CTS+ and CTS- more often than DA-insensitive neurons (P less than 0.01). The effect of DA was usually similar to the effect of rewarding stimuli and their predicting CTS+ and was opposite to the effect of aversive stimuli and their predicting CTS-. 5. The proportion of NE-sensitive neurons that responded to rewarding and aversive stimuli was the same as the proportion of NE-insensitive neurons that responded to the same stimuli. NE-sensitive neurons responded to CTS+ and CTS- more often than NE-insensitive neurons (P less than 0.01). The effect of NE was usually similar to the effect of rewarding stimuli and predicting CTS+, and opposite to the effect of aversive stimuli and predicting CTS-. 6. ACh-sensitive neurons responded to aversive stimuli and predicting CTS- more often than ACh-insensitive neurons (P less than 0.01), but the response ratio of ACh-sensitive neurons to rewarding stimuli was similar to that of ACh-sensitive neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

Control of trigeminal motoneurons from the cerebellar interpositus nucleus of the guinea pig.

1. Effects of stimulation of the cerebellar interpositus nucleus (IPN) on jaw reflexes and trigeminal motoneurons were studied along with the route responsible for the effects in ketamine-anesthetized guinea pigs. 2. Stimulation in the IPN evoked a bilateral, ipsilaterally dominant, short-latency reciprocal effect on jaw reflexes: a depression of the jaw-closing masseteric reflex and a facilitation of the jaw-opening digastric reflex. This reciprocal phase was followed by a non-reciprocal facilitatory phase. 3. Stimulation in the IPN evoked a short-latency, strychnine-sensitive inhibitory postsynaptic potential (IPSP) followed by a rebound depolarizing potential in the jaw-closing masseter motoneurons (MAMNs) and an excitatory postsynaptic potential (EPSP) in the jaw-opening anterior digastric motoneurons (ADMNs). The time course of the intracellular response of MAMNs to the IPN stimulation was similar to that of the IPN-induced effects on the jaw-closing reflex. In contrast, the duration of the IPN-induced EPSP in ADMNs was shorter than the IPN-induced facilitation of the jaw-opening reflex. 4. After the IPN neurons were lost by injection of kainic acid into the nucleus, the reciprocal effect of the IPN stimulation on the jaw reflexes could not be seen, even though the projection fibers from the trigeminal sensory nucleus to the IPN remained essentially intact. 5. Stimulation in the superior cerebellar peduncle (SP) induced the same reciprocal effect on the jaw reflexes as the IPN stimulation. A lesion of the SP virtually abolished the reciprocal effect on the jaw reflexes of stimulation in the IPN ipsilateral with reference to the SP lesion. 6. Transection of the brain stem at the level immediately caudal to the red nucleus did not affect the reciprocal effect of the IPN stimulation on the jaw reflexes. 7. We conclude that the IPN output bilaterally induces an inhibition of jaw-closing MAMNs and an excitation of jaw-opening ADMNs, oligosynaptically by way of a direct cerebelloreticular projection system via the SP.

Animals↗

[Antihypertensive effect of felodipine, a new calcium antagonist].

The antihypertensive effect of felodipine was examined in various hypertensive animal models. In spontaneously hypertensive rats, felodipine administered singly at 0.1-1.0 mg/kg (p.o.) had a dose-dependent antihypertensive effect. Nifedipine was effective at 1 mg/kg. In the repeated oral administration experiment, both the maximum decrease in blood pressure and duration of the effect increased gradually and reached steady levels at 3 weeks of administration, which were maintained thereafter. Similar results were noted with nifedipine, but felodipine was longer-acting (4-6 hr) in the steady state than nifedipine (1-2 hr). No development of tolerance was observed during the administration period. In DOCA-salt and renal hypertensive (2K1C) rats, felodipine at 0.1-0.5 mg/kg (p.o.) was superior to nifedipine in the maximum decrease in blood pressure and duration of the effect. Felodipine up to 1 mg/kg (p.o.) caused no significant heart rate increase in any rat model. In renal hypertensive (2K2C) dogs given felodipine at 0.2-0.5 mg/kg (p.o.), the effect lasted for 2 hr after injection. This felodipine effect was stronger and longer lasting than the nifedipine one. At 0.5 mg/kg of felodipine, the heart rate was transiently increased. The present results show that felodipine has a stronger and long-lasting antihypertensive effect than nifedipine in the hypertension models.

Administration, Oral↗

Effect of recombinant human granulocyte colony-stimulating factor on survival in lethally irradiated mice.

Repeated injections of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to lethally irradiated mice increased the rate of animal survival. Dose modification factor was 1.20 when 4.5 micrograms/mouse of rhG-CSF was given daily for 14 days after whole body irradiation. Haematological examinations revealed that rhG-CSF increased the number of blood-circulating leukocytes, neutrophils, monocytes and erythrocytes, but not that of lymphocytes and thrombocytes. Spleen weight and number of endogenous spleen colonies were also increased by rhG-CSF treatment compared with the values for mice irradiated only.

Animals↗

Synchronous double malignancy: adenocarcinoma of lung and malignant astrocytoma induced by asbestos exposure.

A 54-year-old male died of cerebellar herniation induced by brain tumor. Radiological examination of this case showed two separate tumorous lesions in the brain and lung. Autopsy proved malignant astrocytoma in the brain and coincidental alveolar cell carcinoma in the lung. He had a history of asbestos exposure for 8 years doing piping work in a shipyard. Furthermore, we detected a large number of asbestos bodies in the lung and one asbestos body in the brain. Therefore, this rare case of double cancer (malignant astrocytoma and lung cancer) might have been induced by asbestos exposure.

Adenocarcinoma↗

Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17.

Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.

Base Sequence↗

[Utility of recombinant human erythropoietin on the anemia of elderly hemodialysis patients].

Recombinant human erythropoietin was administered to 59 patients over 65 years of age receiving maintenance hemodialysis treatment in Kyoto and Shiga district, in order to evaluate its utility on renal anemia. After 6 months of administration, the hematocrit rose from 20.8 +/- 3.5% to 28.0 +/- 3.7% with concomitant improvement of subjective symptoms related to anemia. Twelve patients developed side effects, in 10 of whom elevation of blood pressure was observed. We found no clinically significant abnormalities in the laboratory data. In conclusion, recombinant human erythropoietin is highly useful in the treatment of renal anemia in elderly hemodialysis patients.

Age Factors↗

Suppressive effect of prostaglandin E1, but not prostacyclin, on ouabain-induced ventricular fibrillation in guinea-pigs.

Arrhythmia was produced by the rapid intravenous injection of ouabain 200 micrograms/kg in anesthetized guinea-pigs. The incidence of ventricular fibrillation (V.F.) induced by the ouabain challenge was significantly decreased by the pretreatment with prostaglandin (PG) E1 5 micrograms/kg or propranolol 0.5 mg/kg, but not with prostacyclin (PGI2) 0.5 or 5 micrograms/kg. Also, a significant number of animals treated with PGE1 or propranolol, but not PGI2, showed recurrent reversion to sinus or ventricular rhythm from V.F. and survived more than 20 min after the ouabain challenge. On the other hand, almost all animals treated with PGI2 produced V.F., which converted to cardiac arrest within 20 min after the ouabain challenge. The finding shows that PGI2 has no protective action on V.F. induced by ouabain in anesthetized guinea-pigs. Involvement of norepinephrine released from sympathetic nerve terminals in ouabain-induced V.F. was assumed.

Animals↗

Clinical application of a newly developed surveying system for designing and fabricating removable partial dentures.

In this paper, some problems in commercially available surveying systems were discussed, and a clinical technique for designing and fabricating clasps by using an improved 'Digital Surveyor' and a computer system were presented. This system has the advantages as follows: (1) morphological factors on abutment teeth could be measured and evaluated using the improved 'Digital Surveyor' and its accessories set, (2) clasps providing with proper mechanical properties according to various conditions in the mouth could be designed and fabricated precisely and easily. It became clear that conventional surveying methods involved empirical rules should be re-examined and replaced by the more rational surveying method like this system.

Computer-Aided Design↗

Three dimensional shape measurement system for residual ridges.

It is very important for design and construction of complete dentures to evaluate the condition of residual ridges of edentulous patients objectively and precisely. The authors have been developing a shape measurement system for residual ridges. In this study, the outline of the system is described and the accuracy of the system is evaluated. The system consists of a high precision laser displacement meter, a working table and its controller, and a personal computer. The working table, on which a plaster model is placed, can move until the end of the moving range at a speed of 0.7 mm/sec. The height of the plaster model was measured intermittently with a frequency of 7 points/sec. To determine the accuracy of this system, experimental plaster models, which simulated the simplified shape of residual ridge, were measured and analyzed. The measurement error was 2.5%, which seemed to be highly accurate. The accuracy of the measurement decreased with the darkness of the color of the plaster model.

Alveolar Bone Loss↗

Influence of dimensional factors and heat treatment on permanent deformation of wrought wire clasps.

The purpose of this study is to examine the fatigue profiles of wrought wire clasps during the clinical use. Cobalt-chromium-nickel alloy wires were bent into circular beams, which dimensions and fabrication methods were similar to the clinical cases. Deflections of 0.5 mm in a normal direction were applied 10,000 times to the tips of clasp arm and permanent deformations were measured. The following results were obtained. 1) The clasp arms with larger cross sectional diameter, shorter length and smaller radius of curvature showed larger amounts of permanent deformation. 2) The amounts of permanent deformation of the clasp arm remarkably decreased by electric resistance soldering and decreased further more by heat treatment at 500 degrees C for 10 minutes after soldering regardless of the number of deflection. From the results of this study, it was concluded that dimensional factors and heat treatment influenced the permanent deformation of the wrought wire clasps remarkably. Therefore, considering these factors, wrought wire clasps could be designed to reduce permanent deformation.

Chemical Phenomena↗

Establishment of a human hepatoblastoma model in athymic nude mice. Producibility of fatty acid-binding protein, alpha-fetoprotein, and alpha 1-acid glycoprotein.

An athymic nude mouse model of human hepatoblastoma, designated HBL-2, was established. HBL-2 produced alpha-fetoprotein (AFP) and the serum level in tumor-bearing mouse was roughly proportional to the tumor weight. Reactivity of AFP to Concanavalin A and Lens culinaris lectins indicated that it contained predominantly fucosylated, non-bisecting N-acetylglucosamine as a sugar moiety. Alpha 1-acid glycoprotein (AAG) was also found in both HBL-2 tumor extract and sera of tumor-bearing mice. The serum level, however, was not proportional to either the tumor weight or the value of the tumor extract. In addition, fatty acid-binding protein (FABP) was detected in approximately 40% of tumor cells and in tumor extract with polyclonal antibody against liver FABP. Thus, HBL-2 is an unique model of human hepatoblastoma, in that it produces FABP in addition to AAG and AFP.

Animals↗

A 5-lipoxygenase inhibitor, FR110302, suppresses airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles in rats.

To study the role of chemical mediators in airway hyperresponsiveness and simultaneous eosinophilia, we examined effects of a potent 5-lipoxygenase inhibitor FR110302 and those of prednisolone, indomethacin, platelet-activating factor (PAF) antagonist (RP-59227) and leukotriene C4 (LTC4) antagonist (ONO-1078) on airway hyperresponsiveness and lung eosinophilia induced by Sephadex particles. Sephadex G200 particles (2.5 mg/kg) were injected intravenously to rats and 3 days later the airway hyperresponsiveness to acetylcholine (ACh) and the eosinophilia in the bronchoalveolar lavage (BAL) fluids were observed. FR110302 (10 mg/kg b.i.d.p.o.) significantly suppressed both of these indicators of asthma. The amounts of immunoreactive LTB4,C4 (i-LTB4, C4) in the BAL fluid were measured by radioimmunoassay. The amounts of i-LTB4,C4 in the FR110302-treated rats were significantly less compared with that in the Sephadex-injected controls. Prednisolone completely inhibited the airway hyperresponsiveness. PAF antagonist and LTC4 antagonist partially inhibited the airway hyperresponsiveness, and indomethacin had no effect. The results indicate that 5-lipoxygenase products play important roles in the Sephadex-induced airway hyperresponsiveness and lung eosinophilia in rats.

Acetylcholine↗