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H Arita

Publications and source records attributed to H Arita.

At least 55 records · Page 3Linked to original sources
PubMed1996

Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases.

Axl, Sky, and Mer, members of an Axl/Sky receptor tyrosine kinase subfamily, are typified by the cell adhesion molecule-related extracellular domain. The product of growth arrest-specific gene 6 (Gas6), structurally homologous to the anticoagulant protein S, was recently identified as the ligand for Axl and Sky, but the ligand for Mer remained unknown. We have now obtained evidence that Gas6 can also function as a ligand for Mer. Co-precipitation analysis, using soluble receptors of Axl, Sky, and Mer (Axl-Fc, Sky-Fc, and Mer-Fc) composed of the extracellular domain of receptors fused to the Fc domain of immunoglobulin G1, clearly showed that Gas6, but not protein S, specifically bound to Axl-Fc, Sky-Fc, and Mer-Fc fusion proteins. Quantitative kinetic analyses using a BIAcore biosensor instrument revealed dissociation constants (Kd) of the binding of rat Gas6 to Axl-Fc, Sky-Fc, and Mer-Fc are 0.4, 2.7, and 29 nM, respectively. We also found that Gas6 stimulated tyrosine phosphorylation of Axl, Sky, and Mer receptors ectopically expressed in Chinese hamster ovary cells. Taken together, these findings suggest that Gas6 is a common ligand for Axl, Sky, and Mer, all known members of an Axl/Sky receptor subfamily.

Animals↗
PubMed1996

Response of tracheal smooth muscle tone to lower brain stem hypoxia in dogs.

We examined effects of central hypoxia on tracheal smooth muscle (TSM) tone, phrenic nerve activity (PNA) and blood pressure (BP) in decerebrated, paralysed, and artificially ventilated dogs. Central hypoxia was induced by injection of N2-saturated saline (5 ml; PO, 25-32 torr) through a catheter in the vertebral artery. The effects of central hypoxia were compared with the responses to central chemoreceptors stimulation, namely central hypercapnia induced by intravertebral injection of high CO2 saline (5 ml; PCO2 90-100 torr, PO2 80-120 torr, pH 7.38-7.42) buffered by HCO3-. Central hypoxia caused relaxation of TSM accompanied by depression of PNA and elevation of BP. In contrast, central hypercapnia evoked tracheal constriction along with respiratory excitation and pressor response. The tracheal relaxation in response to central hypoxia occurred with onset and peak latencies similar to those observed in PNA depression and BP elevation. This suggests a common source for the synaptic inputs to three distinct control systems involved in cardiovascular, respiratory and airway functions. Such neuronal substrate is considered to be activated by central hypoxia.

Animals↗
PubMed1996

Characterization of a high-affinity and specific binding site for Gas6.

We have purified a novel growth-potentiating factor and demonstrated that the factor is coded by the gas6 gene. Moreover, we have suggested the presence of a Gas6 receptor on rat vascular smooth muscle cells. In this study, we further analyzed the binding of Gas6 to its receptor. Tissue and cellular distribution of the binding activity of (125)I-labeled Gas6 showed that the binding site existed in many but a limited range of tissues and cell types. Further characterization of the binding of [(125)I]Gas6 using HOS cells demonstrated that the specific binding was dependent on the presence of Ca(2+). Chemical cross-linking of [(125)I]Gas6 to HOS cells resulted in the formation of a high-molecular-mass complex, suggesting the presence of a high-molecular-weight receptor.

Animals↗
PubMed1996

Prevention of growth arrest-induced cell death of vascular smooth muscle cells by a product of growth arrest-specific gene, gas6.

We have purified Gas6 as a growth-potentiating factor for vascular smooth muscle cells (VSMCs) [Nakano, T. et al. (1995) J. Biol. Chem. 270, 5702-5705]. However, specific production of Gas6 in growth-arrested cells raises an intriguing question as to the physiological function of Gas6. In this study, we found that serum-starved VSMCs secreted some survival factors and depletion of the factors induced cell death of VSMCs. Finally, we demonstrated that cell death was prevented by the addition of Gas6, suggesting that one of the major biological activities of Gas6 is protection of growth-arrested VSMCs from death.

Animals↗
PubMed1996

Nonadrenergic relaxation of the cat cervical trachea evoked by stimulation in the lateral hypothalamic area.

The purpose of this study was to evaluate hypothalamic contributions to control of tracheal tone. We found hypothalamic sites where electrical stimulation (60-90 microA: 1 ms pulse duration: 50 Hz: 5-10 s) and microinjection of L-glutamate (5-50 nmol) produced tracheal relaxation responses along with decreased blood pressure and heart rate in anesthetized, spontaneously breathing cats. Responsive sites were located in anterior (LHAa) and tuberal (LHAt) regions of the lateral hypothalamic area indicating that neuronal cells in those regions are responsible for development of tracheal relaxation. In a second experiment, we evaluated possible pathways mediating the tracheal relaxation response elicited by LHA stimulation. Tracheal relaxation was not attenuated by beta-adrenergic blockade (propranolol i.v., 0.2-0.5 mg/kg); the response is mediated by nonadrenergic mechanisms Muscarinic blockade (atropine i.v.) at doses of 0.05-0.1 mg/kg almost abolished tracheal tone during spontaneous breathing, and LHA stimulation evoked a small, insignificant reduction of tracheal tone. Cervical vagotomy completely abolished the trachea tone, and LHA stimulation no longer evoked the tracheal relaxation. These results indicate the existence of a nonadrenergic descending pathway within the vagal efferents, which is linked with behavioral control arising from LHA, and causes trachea relaxation.

Adrenergic Fibers↗
PubMed1996

Cardiorespiratory changes when balancing one's whole body on one leg with eyes closed.

Postural control system has been extensively studied in terms of somatic motor function, but little is known about its connection with human autonomic function. The purpose of this study was to determine the cardiorespiratory changes in response to the 3-min load that was performed by balancing one's whole body on one leg with eyes closed (SOLEC load) or eyes open (SOLEO load) in 11 healthy young subjects (5 males and 6 females, mean age 20.8 +/- 1.9 year). Blood pressure (BP), heart rate (HR), respiratory rate (RR), inspiratory and expiratory duration (Ti and Te), tidal volume (VT), and oxygen uptake (VO2) were measured before, during, and after the load. The SOLEC load produced significant increases in HR and systolic BP within 1 min. There were further increases in systolic and diastolic BP during the late period of the load. Metabolic rate (VO2) showed a gradual increase during the SOLEC load, indicating that the late responses would be partly due to metabolic alteration. The early responses are considered to be mediated neurally through the postural control system which receives the afferent inputs arising from vestibular system and from muscle proprioceptors of the leg. In contrast, SOLEO load caused small insignificant changes in BP, HR, VT, and VO2, suggesting that a visual input is essential for balancing a postural change. The balance test with eyes closed may have value in a clinical neurological rehabilitation setting.

Adult↗
PubMed1995

Differences in motor control in the bronchus and extrathoracic trachea.

The motor control of the bronchus and extrathoracic trachea was evaluated by continuously measuring bronchial diameter and tracheal muscle tension as well as phrenic nerve activity in decerebrated, paralyzed, artificially ventilated dogs. Spontaneous rhythmic changes in bronchial diameter and tracheal muscle tension occurred in phase with phrenic burst during mechanical ventilation and during apnea induced by disconnecting the ventilator. There was a small but consistent difference in the timing of their rhythmic activities; bronchial constriction started at mid-inspiration, whereas tracheal contraction began just prior to the end of inspiration. Both were active in the post-inspiratory phase. Both hypercapnia and apnea caused an enhanced rhythmic constriction of the bronchus, while evoking a tonic contraction of the trachea. Intermittent electric stimulation of the efferent vagus nerves revealed that repetitive stimulation with a short intermission was necessary to evoke a sustained constriction of the bronchus, and that the bronchus could maintain the sustained constriction only transiently. These results indicate that the motor control of the bronchus and extrathoracic trachea are distinct. The central nervous system may contribute to the difference in timing of the contraction between tracheal and bronchial smooth muscle. However, the difference in response to electric stimulation of the nervus vagus may be attributed to the peripheral neuromuscular system.

Animals↗
PubMed1995

Stimulation of sky receptor tyrosine kinase by the product of growth arrest-specific gene 6.

Sky (also called Rse, Brt, and Tyro3) is a member of a subfamily of related receptor tyrosine kinases, including Axl/Ufo/Ark and c-Eyk/Mer. We obtained evidence that Gas6 (the product of growth arrest-specific gene 6) is a ligand of the Sky receptor tyrosine kinase. Gas6, but not protein S (an anticoagulant protein structurally similar to Gas6), specifically bound to the soluble form of Sky (Sky-Fc), composed of the extracellular domain of Sky fused to the Fc domain of human immunoglobulin G1. The native and recombinant Gas6, but not protein S, stimulated tyrosine phosphorylation of Sky ectopically expressed in Chinese hamster ovary cells. Stimulation of Sky in response to Gas6 was inhibited by Sky-Fc. The half-maximal concentration of Gas6 that stimulated Sky was about 1 nM. Thus, Gas6 as a ligand for Sky specifically binds to and stimulates Sky receptor tyrosine kinase.

Animals↗
PubMed1995

Serotonergic cells in nucleus raphe pallidus provide tonic drive to posterior cricoarytenoid motoneurons via 5-hydroxytryptamine2 receptors in cats.

Microinjection of serotonin and 5-hydroxytryptamine2 (5-HT2) agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) in nucleus ambiguus caused excitation of posterior cricoarytenoid (PCA) muscles of the larynx in anesthetized, spontaneously breathing cats. Intravenous administration of 5-HT2 antagonist ketanserin produced complete block of excitatory effect of DOM injection. Electrical stimulation of nucleus raphe pallidus caused excitation of PCA activity, that was blocked by pretreatment of ketanserin. These results indicate that serotonergic cells in the raphe pallidus provide tonic drive to medullary PCA motoneurons through 5-HT2 receptors.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1995

Glycosylation-dependent binding of pancreatic type I phospholipase A2 to its specific receptor.

Pancreatic group I phospholipase A2 (PLA2-I) elicits various biological responses via its specific receptor. The PLA2-I binding to its recombinant soluble receptor was considerably reduced after Peptide: N-glycosidase F treatment of the receptor. In cultured bovine smooth muscle cells, treatment with tunicamycin, a N-glycosylation inhibitor, resulted in a decrease in the number of PLA2-I receptor. In addition, the PLA2-I binding was blocked by the addition of a lectin, Wheat germ agglutinin. These results suggest an involvement of N-linked oligosaccharides of the PLA2-I receptor for its ligand recognition.

Animals↗
PubMed1995

Vascular smooth muscle cell-derived, Gla-containing growth-potentiating factor for Ca(2+)-mobilizing growth factors.

Proliferation of vascular smooth muscle cells (VSMC) is triggered by two types of growth factors. One activates tyrosine kinase-type receptors and the other activates G-protein-coupled receptors. We found that a conditioned medium of rat VSMC contained a growth-potentiating activity for the latter type of growth factor, and we purified a 70-kDa growth-potentiating factor (GPF) from the conditioned medium. Analyses of GPF and its cDNA revealed GPF to be a gamma-carboxyglutamic acid-containing protein encoded by a growth arrest-specific gene, gas6, which related to protein S. GPF specifically potentiated cell proliferation mediated by Ca(2+)-mobilizing receptors. The presence of a specific binding site suggests that the effect of GPF is mediated by a receptor. Thus, GPF may be a new type of extracellular factor regulating VSMC proliferation.

Amino Acid Sequence↗
PubMed1995

Two distinct descending inputs to the cricothyroid motoneuron in the medulla originating from the amygdala and the lateral hypothalamic area.

1. The retrograde labelling study revealed that there are at least two independent descending pathways from the limbic system to the ventral medulla, i.e., the hypothalamo-medullary pathway and the amygdalo-medullary pathway. 2. The stimulation in the lateral hypothalamic area produced parasympathetic excitation and vocalization response: the recruited motor unit of CT muscle occurred in the late expiratory phase. By contrast, the stimulation at the medial part of the amygdala evoked sympathetic excitation and expiratory braking: the recruited motor unit of CT muscle occurred in the early expiratory phase or in the post-in-spiratory phase. 3. The present physiological study provided further important information on dual innervation of the cricothyroid muscle of the larynx: one motor unit with inspiratory firing is generated in the medulla, whereas the other motor unit with expiratory firing is evoked by a descending input from the limbic system.

Amygdala↗
PubMed1995

Pancreatic-type phospholipase A2 activates prostaglandin E2 production in rat mesangial cells by receptor binding reaction.

Our earlier studies have shown that mammalian pancreatic group I phospholipase A2 (PLA2-I) has its specific receptor (PLA2 receptor) on a wide range of mammalian cells and that the receptor-binding capability of PLA2-I is a property of this molecule separable from its enzymatic activity. To clarify whether PLA2 activity is required for eliciting a biological response via the receptor or not, we examined the enzymatic activity of PLA2-I/PLA2 receptor complex and the inducibility of prostaglandin (PG) E2 production in rat mesangial cells by mutant PLA2s-I. Using a recombinant soluble PLA2 receptor, we first found that PLA2-I could not hydrolyze a phospholipid substrate when complexed with the receptor. In the next experiment using various mutant porcine PLA2s-I, we found that PGE2 production in rat mesangial cells could be induced by a mutant PLA2-I which retained the receptor-binding activity but had almost completely lost its enzymatic activity. These findings indicate that the enzyme action of PLA2-I is not required for a PLA2-I-induced biological response, i.e., the augmentation of PGE2 production in rat mesangial cells.

Animals↗
PubMed1995

[Anesthetic management for laparoscopic cholecystectomy in a patient with dilated cardiomyopathy].

A 55-year-old female with dilated cardiomyopathy was scheduled for laparoscopic cholecystectomy under general anesthesia. Pre-operative tests revealed abnormal ECG and hypokinesis of left ventricular wall motion on echocardiography. A detailed medical examination resulted in the diagnosis of dilated cardiomyopathy, although there was a very mild decrease in cardiac function. We determined that laparoscopic cholecystectomy could be safely carried out under general anesthesia if pneumoperitoneum pressure was kept low. Anesthesia was induced with diazepam 3.75 mg, fentanyl 75 micrograms, thiopental sodium 25 mg and vecuronium 6 mg. Anesthesia was maintained with isoflurane-nitrous oxide-oxygen. From the induction to the end of the operation, dopamine was infused. Increased heart rate and blood pressure were noted for a short time at the induction and at the time of first pneumoperitoneum. Thereafter, no considerable hemodynamic changes occurred. We therefore consider that laparoscopic cholecystectomy under low pressure pneumoperitoneum is appropriate for dilated cardiomyopathy when there is no accompanying heart failure or when only mildly decreased cardiac function exists, such as in this case.

Anesthesia, General↗
PubMed1995

[Anesthesia for thoracoscopic laser ablation of bullae in a patient with severe bullous emphysema].

A 46-year-old male underwent laser-ablation of emphysematous bullae of the right lung via thoracoscope. For almost a year he had been bedridden because of severe dyspnea on exertion, in spite of medication and oxygen therapy. He also complained of orthopnea at rest and had suffered from body weight loss of 10 kg during the preceding year. Radiologic examination revealed emphysemotous lung with bilateral giant bullae. In spirogram, forced vital capacity in 1 second was markedly low (0.45 l, corresponding to 19% in %FVC1.0), vital capacity moderately depressed (2.41 l, 64%) and residual volume markedly elevated (5.85 l, 387%). Anesthesia was induced and maintained using the combination of thoracic-epidural anesthesia and intravenous anesthesia (midazolam and fentanyl). One lung ventilation (OLV) was used to facilitate thoracoscopic procedure. Mechanical ventilation was conducted at first with an anesthesia ventilator. As the duration of OLV was prolonged, however, the peak airway pressure increased, the tidal volume decreased and the value of percutaneous arterial hemoglobin saturation (SpO2) declined. In order to keep adequate oxygenation, brief periods of two lung ventilation (TLV) became necessary, in addition to the application of continuous positive airway pressure to the non-dependent lung. When ventilation was changed from volume-cycled ventilation to pressure-cycled and from using an anesthesia ventilator to a critical care type ventilator (Servo 900C), sufficient tidal volume was achieved with lower peak airway pressure, producing reasonable Spo2 value with much less frequent TLV. At the end of the surgery bronchopleural fistulae still persisted, with resultant air leak of about 50% of inspired tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1995

Secretory phospholipase A2 inhibitors. Possible new anti-inflammatory agents.

Secretory phospholipase A2 (sPLA2) is now clearly considered to be involved in the pathogenesis of both experimental and clinical inflammatory processes. This has led academic and pharmaceutical industry researchers to expend enormous efforts to identify specific sPLA2 inhibitors to better understand the role of this enzyme in biological systems and to enable its clinical use in the treatment of inflammation and related disorders. Presented here is a brief review of the biological activity of sPLA2 inhibitors and diseases that may be postulated as their possible targets. Also discussed are problems associated with the evaluation of sPLA2 inhibitors for their selectivity and specificity.

Animals↗