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Biomedical subjects

H Arita

Publications and source records attributed to H Arita.

At least 37 records · Page 2Linked to original sources
PubMed1999

Suppression of murine endotoxic shock by sPLA2 inhibitor, indoxam, through group IIA sPLA2-independent mechanisms.

Endotoxic shock is a systemic inflammatory process, involving a variety of proinflammatory mediators. Two types of secretory phospholipase A2 (sPLA2) have been implicated in this process. Group IB sPLA2 (PLA2-IB) binds to the PLA2 receptor (PLA2R), and PLA2R-deficient mice exhibit resistance to endotoxin-induced lethality with reduced plasma levels of proinflammatory cytokines, such as TNF-alpha. Group IIA sPLA2 (PLA2-IIA) is found in many tissues and cell types, and local and systemic levels are elevated under numerous inflammatory conditions including sepsis. In this study, we investigated the effect of a specific sPLA2 inhibitor, indoxam, on murine endotoxic shock. Indoxam suppressed the elevation of plasma TNF-alpha with a similar potency in PLA2-IIA-expressing and PLA2-IIA-deficient mice after LPS challenge. In PLA2-IIA-deficient mice, indoxam also suppressed the elevation of plasma IL-1beta, IL-6 and NO, and prolonged survival after LPS challenge. Indoxam was found to block the PLA2-IB binding to murine PLA2R with a high potency (Ki=30 nM). The inhibitory effects of indoxam on the LPS-induced elevation of plasma TNF-alpha levels could not be observed in mice deficient in PLA2R. These findings suggest that indoxam blocks the production of proinflammatory cytokines during endotoxemia through PLA2-IIA-independent mechanisms, possibly via blockade of the PLA2R function.

Animals↗
PubMed1999

[Success rate of anesthesia induction using target-controlled infusion of propofol with fentanyl].

Twenty-one patients were studied to compare the success rate of anesthesia induction using target-controlled infusion of propofol with and without fentanyl. All patients were premedicated with atropine 0.5 mg and hydroxyzine 25-50 mg. Five minutes after intravenous administration of fentanyl 2 micrograms.kg-1, patients were given infusions of propofol designed to achieve target blood concentrations of 3 micrograms.kg-1. Loss of verbal contact was regarded as successful induction. The success rate of anesthesia induction within three minutes of achieving the target concentration was 90%. Pain on injection and reduction in blood pressure were infrequent. Selecting a target concentration of 3 micrograms.kg-1 with fentanyl 2 micrograms.kg-1 can be expected to successfully induce anesthesia in the majority of patients without major hemodynamic side effects and pain on injection.

Adult↗
PubMed1999

[Anesthetic management of a patient with Saber-sheath trachea].

A 65-year-old man was scheduled for total gastrectomy. Preoperative chest radiograph showed significant narrowing of the trachea. On chest CT scan the trachea was U-shaped (tracheal index = 36%) and was diagnosed as saber-sheath trachea. During general anesthesia we took care to reduce the irritation by the endotracheal tube, particularly during intubation, and to avoid excessively high airway pressure. The trachea was watched carefully by bronchoscopy after intubation and during extubation not to neglect any complication. There was no complication after the operation.

Aged↗
PubMed1998

Type IB secretory phospholipase A2 is contained in insulin secretory granules of pancreatic islet beta-cells and is co-secreted with insulin from glucose-stimulated islets.

Stimulation of pancreatic islets with d-glucose induces insulin secretion from secretory granules contained within the islet beta-cells. Accumulating evidence suggests that secretory phospholipases A2 (sPLA2) may play a role in the distal events of secretory processes in many different cell types. Since intact pancreatic islets have been reported to contain sPLA2, it was of interest to determine the cellular and subcellular localization of the sPLA2 enzymes in pancreatic islets. Our findings indicate that rat pancreatic islets express mRNA for both types IB and IIA sPLA2 enzymes and mRNA for an sPLA2 membrane receptor. Immunoblotting analyses with antibodies directed against type IB sPLA2 or against type IIA sPLA2 indicate that the type IB isoform is much more abundant than the type IIA isoform in islets. Studies with purified populations of islet beta-cells prepared from dispersed islet cells by fluorescence-activated cell sorting indicate that both sPLA2 activity and type IB sPLA2 immunoreactive protein are substantially more abundant in beta-cells than in non-beta-cells. Subcellular fractionation studies indicate that sPLA2 activity and type IB sPLA2 immunoreactive protein are contained in insulin secretory granules. Stimulation of intact islets with insulin secretagogues results in the co-secretion of insulin and of sPLA2 activity and type IB sPLA2 immunoreactive protein into the incubation medium. These findings raise the possibility that type IB sPLA2 participates in the secretory process of pancreatic islet beta-cells.

Animals↗
PubMed1998

Dynamics of human cardiorespiratory responses to standing on one leg with eyes closed.

The 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 1-min balance test that was performed by standing on one leg with eyes closed (SOLEC) or eyes open (SOLEO) in 12 healthy young women [mean age 20.7 (SD 3.3) years]. Heart rate (HR), respiratory rate (RR), duration of inspiration and expiration, tidal volume (VT), and oxygen uptake (VO2) were measured during the test. The SOLEC test produced rapid increases in HR at the onset. There were significant increases in HR later during the test (P < 0.05). Metabolic rate (VO2) showed a gradual increase during the SOLEC test, indicating that the late responses could have been partly due to metabolic changes. The RR increased significantly at the onset of the test (P < 0.05), and remained elevated until the end of the test. The early responses were considered to be mediated neurally through the postural control system which receives the afferent inputs arising from the vestibular system and from muscle proprioceptors of the leg. In contrast, SOLEO caused small insignificant changes in HR, RR, VT and VO2, suggesting that a visual input is essential for balancing a postural change. The SOLEC test may have potential as a test of autonomic function.

Adolescent↗
PubMed1998

Production of eosinophil chemotactic factor by CD8+ T-cells in Toxocara canis-infected mice.

Production of eosinophil chemotactic factor by T-lymphocytes (ECF-L) was examined in Toxocara canis-infected mice. When spleen cells from T. canis-infected mice were cultured in serum-free RPMI1640, ECF-L production was detectable in an antigen-specific manner. The ECF-L production peaked at day 9 post-infection and then decreased. Depletion of Thy 1.2+ cells or CD8+ cells completely abrogated ECF-L production, whereas depletion of CD4+ cells did not, indicating that CD8+ T-cells are involved in the production of ECF-L. When bone marrow eosinophils obtained from T. canis-infected mice were preincubated with ECF-L, their chemotactic reactivity to parasite-derived ECFs was enhanced, whereas that of peritoneal cavity-derived eosinophils was not. Thus, ECF-L seems to be important not only as a chemoattractant but also as an activator of the chemotactic reactivity of naive eosinophils to the parasite-derived ECF in T. canis infection.

Animals↗
PubMed1998

GABAergic inhibition of hiccup-like reflex induced by electrical stimulation in medulla of cats.

We hypothesize that the hiccup reflex is actively inhibited through GABA(B) receptor within central connections of the hiccup reflex arc. Because the hiccup-like reflex can be elicited by electrical stimulation to a limited area within the medullary reticular formation, the hiccup-evoking site (HES), electrical stimulation (50-100 microA, three train pulses at 20 Hz) was delivered to HES by means of a metal electrode containing 1.0 mM baclofen, in anesthetized spontaneously breathing cats. The evoked response was characterized by a brief powerful increase in diaphragmatic activity and a temporal suppression of the posterior cricoarytenoid muscle, laryngeal dilator, which corresponded to the fixed motor pattern of hiccup reflex. The hiccup-like response was rapidly suppressed after microinjection of baclofen (0.1-0.5 nmol) into HES, indicating that HES has GABA(B) receptors. In the other experiments, to histologically examine the inputs to the hiccup reflex arc, unconjugated cholera toxin subunit B (UCTB) was injected into HES. Following injections of UCTB, retrogradely labelled cells were found distributed in various areas of the lower brainstem. Among these areas, the nucleus raphe magnus (RM) is reported to have GABA-containing cells. It is thus hypothesized that RM is most likely to be the source of the GABAergic inhibitory inputs to the hiccup reflex arc.

Animals↗
PubMed1998

Stereotyped yawning responses induced by electrical and chemical stimulation of paraventricular nucleus of the rat.

Yawning was evoked by electrical or chemical stimulation in the paraventricular nucleus (PVN) of anesthetized, spontaneously breathing rats. To evaluate physiological aspects of yawning, we monitored polygraphic measures as follows; a coordinated motor pattern of yawning was assessed by monitoring breathing [intercostal electromyogram (EMG)], mouth opening (digastric EMG), and stretching of the trunk (back EMG). We also recorded blood pressure (BP), heart rate, and the electrocorticogram (ECoG) to evaluate autonomic function and arousal responses during yawning. A stereotyped yawning response was reproducibly evoked by electrical stimulation or microinjection of -glutamate or NOC-7, a nitric oxide (NO)-releasing compound, into the PVN. The stereotyped yawning response consisted of two sequential events, an initial response represented a depressor response and an arousal shift in the ECoG to lower voltage and faster rhythms. These initial changes were followed by a yawning behavior characterized by a single large inspiration with mouth opening and stretching of the trunk. A similar sequence of events occurred during spontaneous yawning; a fall in BP and ECoG arousal preceded a yawning behavior. An increase in the frequency of spontaneous yawns was also observed after microinjection of -glutamate or NOC-7 into the PVN. Intravenous administration of NG-monomethyl--arginine, an inhibitor of nitric oxide synthase (NOS), prevented the stereotyped yawning response evoked by chemical stimulation of the PVN. Histological examination revealed that effective sites for the yawning responses were located in the medial part of the rostral PVN, the site of parvocellular and magnocellular neurons. NADPH-diaphorase histochemistry showed the existence of NOS-containing cells in yawning-evoked sites of the PVN. In summary, the sequential events of yawning may be generated by NOS-containing parvocellular neurons in the medial part of the rostral PVN projecting to the lower brain stem.

Animals↗
PubMed1998

[Body temperature changes during combined inhalational and epidural anesthesia].

We investigated the effects of combined inhalational and lumbar epidural anesthesia on body temperature in 8 women for long-lasting lower abdominal surgery. Probes for forehead deep temperature and skin-surface temperatures were placed on the forehead, forearm, fingertip and toe tip on patients' arrival at the operating room. Tympanic membrane temperature was also measured. Lumbar epidural block was established with 2% lidocaine 10 ml. Twenty minutes later, general anesthesia was induced and maintained with nitrous oxide-oxygen-isoflurane. Epidural anesthesia was maintained with intermittent dose of 1% mepivacaine. Before the end of surgery, isoflurane concentration was increased from about 0.5% to 2% and was maintained at this level for 20 minutes, after which it was reduced. With the establishment of epidural blockade, toe tip temperature increased and fingertip temperature decreased, while core temperature remained unchanged. After induction of general anesthesia, fingertip temperature increased, while core temperature decreased. The core temperature drop during the anesthetic induction was significantly affected by the increase in toe tip temperature. Before the end of surgery, core temperature remained at a reduced but constant level, while fingertip temperature continued to decrease. With the application of 2% isoflurane, fingertip temperature increased, while core temperature decreased. The core temperature drop was significantly affected by the increase in fingertip temperature. After the reduction of isoflurane concentration, these temperature changes were reversed fully. At the end of surgery, fingertip temperature decreased, while core temperature increased. During mild hypothermia, isoflurane depressed thermoregulatory vasoconstriction dose-dependently until its concentration reached 0.6-0.7%. In conclusion, anesthetics-induced redistribution of body heat significantly affects the core temperature throughout anesthesia. Peripheral hypothermia results in core temperature drop when the redistribution is induced by anesthetics. Thermoregulatory vasoconstriction may not only suppress heat loss but also increase core temperature through centralization of body heat.

Adult↗
PubMed1997

Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice.

Mammals possess various types of secretory phospholipase A2, which differ in the primary structure and tissue distribution. The phosholipase A2 receptor (PLA2R) recognizes group IB phospholipase A2 (PLA2-IB) and mediates the PLA2-IB-induced biological responses in non-digestive organs, including eicosanoid production and contraction of airway smooth muscles. In this study, we generated PLA2R-deficient mice to define its biological roles further. These mice are viable, fertile, and without evident histopathological abnormalities. There was no difference in the clearance of circulating PLA2-IB between wild-type and mutant mice. After challenge with bacterial lipopolysaccharide (LPS), PLA2R-deficient mice exhibited longer survival than wild-type mice. The mutant mice were also resistant to lethal effects of exogenous PLA2-IB after sensitization with sublethal dose of LPS. The plasma levels of tumor necrosis factor-alpha and interleukin-1beta elevated after LPS treatment were significantly reduced in mutant mice compared with wild-type mice. These findings suggest a potential role of PLA2R in the progression of endotoxic shock.

Animals↗
PubMed1997

Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6.

Gas6, a product of a growth arrest-specific gene 6, potentiates proliferation of vascular smooth muscle cells and prevents cell death of vascular smooth muscle cells. It has been also demonstrated that Gas6 is a ligand of receptor tyrosine kinases Axl, Sky, and Mer. Gas6 contains gamma-carboxyglutamic acid residues, which are found in some blood coagulation factors and mediate the interaction of the coagulation factors with negatively charged phospholipid. In this study, we clarified that Gas6 specifically bound to phosphatidylserine and the binding was dependent on Ca2+ and gamma-carboxyglutamic acid residues. Furthermore, we found that U937 cells, which express Gas6 receptor on their surfaces, adhered to phosphatidylserine-coated enzyme-linked immunosorbent assay (ELISA) plate only in the presence of Gas6 and Ca2+. U937 cells also bound to ELISA plate coated with phosphatidylinositol, but the binding was independent of Gas6 and Ca2+. On the other hand, U937 cells did not adhere to phosphatidylcholine- or phosphatidylethanolamine-coated ELISA plate even in the presence of Gas6 and Ca2+. These findings suggest that Gas6 may play a role in recognition of cells exposing phosphatidylserine on their surfaces by phagocytic cells, which is supposed to be one of the mechanisms for clearing dying cells.

Animals↗
PubMed1997

Roles of gamma-carboxylation and a sex hormone-binding globulin-like domain in receptor-binding and in biological activities of Gas6.

Gas6 is a ligand for an Axl/Sky receptor tyrosine kinase subfamily and has a structure composed of a Gla domain, four EGF-like domains and a C-terminal sex hormone-binding globulin (SHBG)-like domain. When examining the role of each domain in receptor-binding and biological activities of Gas6, we found that receptor-binding and mitogenic activities were markedly reduced by inhibiting gamma-carboxylation of the Gla domain, while a Gas6 mutant composed of only an SHBG-like domain retained both of these activities. Thus, the SHBG-like domain is apparently an entity indispensable for Gas6 activities, and gamma-carboxylation of the Gla domain has a regulatory role in retaining the activity of native Gas6.

3T3 Cells↗
PubMed1997

Requirement of gamma-carboxyglutamic acid residues for the biological activity of Gas6: contribution of endogenous Gas6 to the proliferation of vascular smooth muscle cells.

Gas6 (encoded by growth-arrest-specific gene 6) is a gamma-carboxyglutamic acid (Gla)-containing protein which is released from growth-arrested vascular smooth muscle cells (VSMCs) and potentiates VSMC proliferation induced by Ca2+-mobilizing growth factors, but not that induced by receptor tyrosine kinases. In this study we examined the importance of Gla residues for the biological activities of Gas6 and tried to assess the importance of endogenous Gas6 in VSMC proliferation. We demonstrated that Gla-deficient Gas6 lacked receptor-binding and growth-potentiating activities. Therefore the vitamin K-dependent modification of Gas6 appeared to be essential for its biological activities. Next we used warfarin, an inhibitor of vitamin K-dependent gamma-carboxylation, to estimate the contribution of endogenous Gas6 to VSMC proliferation. Warfarin markedly inhibited the thrombin-induced proliferation of VSMC without affecting the mRNA or protein expression of Gas6. Therefore the inhibition seems to be due to prevention of the vitamin K-dependent modification of Gas6. However, warfarin did not affect epidermal growth factor-induced proliferation. A neutralizing antibody against Gas6 gave a similar result, i.e. it inhibited thrombin-induced VSMC proliferation but not that induced by epidermal growth factor. These results indicate that endogenously produced Gas6 is very important for VSMC proliferation induced by Ca2+-mobilizing growth factors.

1-Carboxyglutamic Acid↗
PubMed1997

Stress down-regulates experimental allergic encephalomyelitis (EAE) but permits activation and localization of autoreactive V beta 8.2+ T cells.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease inducible by encephalitogenic helper T cells expressing V beta 8.2. In this study, we examined the relationship between the stressor-induced alternation of clinical EAE and the induction of autoreactive T cells using Lewis rats. Animals were immersed for 5 min in a water bath maintained at 44 degrees C continuously for 10 or 13 days, before or after the immunization of the encephalitogenic peptide, respectively. Stress administrations after the immunization clearly diminished the severity of clinical EAE, and delayed the onset of disease. On the other hand, stress administrations prior to the immunization resulted in the marginal suppression of clinical EAE. Splenocytes of the stressed rats showed, however, comparative proliferative responses to the encephalitogenic peptide or mitogens with that of the control rats. Moreover, higher level of V beta 8.2 mRNA expression was detected in the spinal cords of the stressed rats than in control rats. Sequence analysis of CDR3 region of TCR cDNA showed that V beta 8.2+ T cells in the spinal cords of the stressed rats possess common features with the biased encephalitogenic T cells. These results suggest that the stressor-induced suppression of clinical EAE is not simply because of the failure of induction of autoreactive T cells, nor localization of the autoreactive T cells in the central nervous system.

Amino Acid Sequence↗
PubMed1997

[Combined spinal and epidural anesthesia for laparotomy in a geriatric patient with severe obstructive lung disease].

Asthma and heavy smoking are the risk factors for postoperative respiratory distress, especially after general anesthesia. We experienced a case of sigmoidectomy in a geriatric patient with severe obstructive lung disease accompanied by asthma and a long history of smoking. The patient was a 70 year old man with 1 second volume of less than 0.6 l, because of asthma and long smoking history of 40 pieces of cigarettes a day for 50 years. We considered that general anesthesia with tracheal intubation might worsen the respiratory state after surgery and chose combined spinal and epidural anesthesia. He received sigmoidectomy under spinal anesthesia with 0.3% dibucaine 2.4 ml combined with epidural anesthesia. As the level of analgesia went up to Th4, the patient complained of dyspnea and he discharged a plenty of sputum. Without any special treatment his dyspnea disappeared spontaneously. During and after the surgery, no exacerbation occurred in his respiratory state. It is suggested that spinal anesthesia combined with epidural anesthesia is useful for a patient with severe obstructive lung disease.

Aged↗
PubMed1996

A receptor tyrosine kinase, Sky, and its ligand Gas 6 are expressed in gonads and support primordial germ cell growth or survival in culture.

Although a number of growth factors and their receptors are involved in the proliferation and differentiation of primordial germ cells (PGCs), the only factor that has been shown to be active in vivo is Steel factor, a ligand for c-Kit. To identify new growth factor receptors that may be required for PGCs function in vivo, we used an reverse transcription-polymerase chain reaction-based strategy to screen for protein kinase genes expressed in PGC-derived embryonic germ cells. We report here that one such gene encoding the receptor tyrosine kinase, Sky, is expressed in both PGCs and their supporting cells in male genital ridges after 11.5 dpc. Interestingly, Sky expression was not detected in female genital ridges, although transcripts were detected in supporting cells in the developing ovary at later stages. Gas 6, a ligand for Sky, was also expressed in interstitial cells which surround Sky positive cells in genital ridges, and, in addition, it supported PGC growth or survival in culture. After birth, Sky expression in testis was restricted to Sertoli cells, and Gas 6 was detected around peritubular cells and Leydig cells. These results suggest that Gas 6-Sky signaling plays a role in PGC growth, sexual differentiation, and Sertoli cell functions in vivo. Sky expression in Sertoli cells diminished by 3 weeks of age, when haploid germ cells first appear. On the other hand, the expression in Sertoli cells was markedly upregulated in the testis of germ cell-deficient W/Wv and jsd/jsd mice. The results suggest that signals from differentiated germ cells suppress Sky gene expression in Sertoli cells. High-resolution chromosomal mapping of Sky is also reported.

Animals↗