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Biomedical subjects

T Mutoh

Publications and source records attributed to T Mutoh.

At least 19 recordsLinked to original sources

Detection of new anti-neutral glycosphingolipids antibodies and their effects on Trk neurotrophin receptors.

We screened sera from patients with various neurological disorders for the presence of anti-neutral glycosphingolipids antibodies and only found them in sera from relapsing polychondritis with limbic encephalitis patients. Neutral glycosphingolipids are resident in membrane lipid rafts where high affinity nerve growth factor (NGF) receptor, Trk is co-localized. Therefore, we examined whether these antibodies influence the action of NGF in NGF-responsive cells. The results strongly suggest that these antibodies enhance NGF-induced Trk autophosphorylation and neurite outgrowth as well as neurofilament M expression. These data strongly indicate that these anti-neutral glycosphingolipids antibodies have a functional impact on NGF-Trk-mediated intracellular signal transduction pathway.

Animals↗

Dynamic behavior of individual cells in developing organotypic brain slices revealed by the photoconvertable protein Kaede.

In recent years, advances in optical imaging methods have facilitated the visualization of events in the developing cortex. In particular, the introduction of DNA encoding fluorescent protein into cells of the embryonic brain allows the visualization of progenitor cells; slice preparations of the cortex then allow the monitoring of the behavior of transfected cells in the context of the living cerebral wall by time-lapse microscopy. Such approaches have provided substantial information about the patterns of neuronal migration. However, as these techniques label large numbers of cells in the ventricular zone (VZ), it is difficult to follow individual cell shape changes or cell behaviors within the VZ, where neuron production and initial migration take place. Here, we report a unique method using the photoconvertable fluorescent protein Kaede, which emits green fluorescence and shifts to emitting red fluorescence upon radiation with UV. Using this method, we were able to follow the behavior of a particular pair of daughter cells among neighboring Kaede-positive cells in the SVZ of mouse brain slices. The spindle shape progenitor divided into two multipolar-shaped daughter cells. The cell-cell borders of daughter cells were clearly visualized, and easily describe the position and distance between two or more cells. The photoconvertable property of Kaede offers a powerful cell marking tool to identify the precise morphology and migratory behaviors of individual cells within living cortical slices.

Animals↗

Sawtooth oscillation in current-carrying plasma in the large helical device.

Sawtooth oscillations have been observed in current-carrying helical plasmas by using electron-cyclotron-emission diagnostics in the Large Helical Device. The plasma current, which is driven by neutral beam injection, reduces the beta threshold of the sawtooth oscillation. When the central q value is increased due to the plasma current, the core region crashes, and, when it is decreased, the edge region crashes annularly. Observed rapid mixture of the plasma in the limited region suggests that these sawtooth crashes are reconnection phenomena. Unlike previous experiments, no precursor oscillation has been observed.

Journal Article↗

Island dynamics in the large-helical-device plasmas.

In the Large Helical Device plasma discharges, the size of an externally imposed island with mode number ( n/m = 1/1) decreases substantially when the plasma is collisionless ( nu(*)< approximately 1) and the beta is finite ( > approximately 0.1%) at the island location. For the collisional plasmas with finite beta, on the other hand, the size of the island increases. However, there is a threshold in terms of the vacuum island size below which the island enlargement is not seen.

Journal Article↗

Tyrosine phosphorylation of the catalytic subunit p110 of phosphatidylinositol-3 kinase induced by HMG-CoA reductase inhibitor inhibits its kinase activity in L6 myoblasts.

Previous studies from this laboratory have shown that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (HCRI) causes apoptotic cell death of a muscle cell-derived cell line, L6 myoblasts, by involving the phosphatidylinositol-3 (PI-3) kinase pathway and tyrosine phosphorylation of several cellular proteins, although the relationship between PI-3 kinase pathway and tyrosine phosphorylation responses remained to be elucidated. Here, we show that HCRI induces tyrosine phosphorylation of catalytic subunit p110 of PI-3 kinase as early as 5 min after addition of HCRI into culture medium. We could not detect the tyrosine phosphorylation of the regulatory subunit p85 of PI-3 kinase under the present experimental conditions. Concomitantly, the kinase activity toward PI in p110 immunoprecipitates was decreased with a similar time course. Furthermore, both herbimycin A and genistein, potent inhibitors of tyrosine kinase activity, inhibited HCRI-induced inhibition of PI-3 kinase activity as well as HCRI-induced apoptotic cell death. Once the catalytic subunit p110 becomes tyrosine-phosphorylated, the regulatory subunit p85 appears to be dissociated from the catalytic subunit, because we observed a decreasing amount of p85 regulatory subunits in p110 immunoprecipitates in response to HCRI treatment. These results strongly suggest the novel function of tyrosine phosphorylation of catalytic subunit p110 of PI-3 kinase in the regulation of its kinase activity. The tyrosine phosphorylation of these catalytic subunits may play an important role in the intracellular signal transduction of apoptotic cell death. To our knowledge, this is the first report that tyrosine phosphorylation of p110 catalytic subunit acts as a negative regulator of its kinase activity.

Animals↗

Observation of the "self-healing" of an error field island in the large helical device.

It was observed that the vacuum magnetic island produced by an external error magnetic field in the large helical device shrank in the presence of plasma. This was evidenced by the disappearance of flat regions in the electron temperature profile obtained by Thomson scattering. This island behavior depended on the magnetic configuration in which the plasmas were produced.

Journal Article↗

Reduction of ion thermal diffusivity associated with the transition of the radial electric field in neutral-beam-heated plasmas in the large helical device.

Recent large helical device experiments revealed that the transition from ion root to electron root occurred for the first time in neutral-beam-heated discharges, where no nonthermal electrons exist. The measured values of the radial electric field were found to be in qualitative agreement with those estimated by neoclassical theory. A clear reduction of ion thermal diffusivity was observed after the mode transition from ion root to electron root as predicted by neoclassical theory when the neoclassical ion loss is more dominant than the anomalous ion loss.

Journal Article↗

Two novel CNRs from the CNR gene cluster have molecular features distinct from those of CNR1 to 8.

Cadherin-related neuronal receptor (CNR) family proteins are known as synaptic cadherins and Reelin receptors. Here we have identified two novel mouse CNR genes, CNRc1 and CNRc2, orthologues of human protocadherin (Pcdh) alpha-c1 and Pcdhalpha-c2, respectively. While the variable large exons of CNRc1 and c2 contain six conserved extracellular cadherin repeats (EC1-6) and are linked to the constant exons, both contain several molecular features distinct from CNR1-8. CNRc1 and c2 lack the Arg-Gly-Asp (RGD) sequence that is conserved in the EC1 of CNR1-8, which is necessary for binding to Reelin. The present studies confirm that CNRc1 and c2 failed to immunoprecipitate with Reelin. In addition, the regulation of novel CNR expression patterns during brain development is slightly different from that of CNR1. The identification of these new CNR genes characterized by their distinct extracellular function and expression is indicative of the novel diversity of the processes of brain structuring and synapse regulation.

Alternative Splicing↗

Acid hydrolase activity of cultured bovine oligodendrocytes.

We measured the activity of several acid hydrolases of cultured oligodendrocytes prepared from adult bovine brain white matter to clarify the biochemical basis of bovine oligodendrocytes in vitro. Lysosomal enzyme activities were assayed by using 4-methylumbelliferyl glycosides as substrates. Lysosomal enzyme activities became higher at 8-11 days in vitro (DIV) than 4 DIV. The enrichment in acid hydrolase specific activities in oligodendrocytes may be associated with lysosomal origin of myelin-like membranes.

Animals↗

Characterization of GTPase-activating proteins for the function of the Rho-family small GTPases in the fission yeast Schizosaccharomyces pombe.

BACKGROUND: The small GTPase Rho1 has been shown to regulate the organization of the actin cytoskeleton and formation of the cell wall in the fission yeast Schizosaccharomyces pombe. Activity of Rho1 must be precisely regulated in vivo, since both increases and decreases in its activity affect cell growth and shape. Thus, it is important to clarify the mechanism by which the activity of Rho1 is regulated in vivo. RESULTS: Seven genes encoding putative GAPs, GTPase-activating proteins, for the function of the Rho-family proteins were isolated from S. pombe. After disruption of these genes, rga1+ was found to play important roles in cell growth and morphogenesis. In rga1 null cells, delocalized F-actin patches and extraordinary thickening of the cell wall and the septum were observed. On the other hand, over-expression of Rga1 produced shrunken or dumpy cells. The phenotype of the rga1 null cells or the Rga1-over-expressing cells was similar to that of cells containing abnormally high or low Rho1 activity, respectively. Moreover, direct association of Rga1 with Rho1 was shown. Rga1 was localized to the cell ends and septum where Rho1 is known to function. CONCLUSIONS: In S. pombe, Rga1 is involved in the F-actin patch localization, cell morphogenesis, regulation of septation, and cell wall synthesis, probably functioning as a GAP for the function of Rho1.

Actins↗

Comparison of sevoflurane with isoflurane for rapid mask induction in midazolam and butorphanol-sedated dogs.

Rapid mask induction can be a useful induction technique for veterinary patients, although it is often accompanied by exaggerated excitement responses in unpremedicated animals (Mutoh et al.: Jpn. J. Vet. Anesth. Surg. 26, 109-116; J. Vet. Med. Sci. 57, 1007-1013; J. Vet. Med. Sci. 57, 1121-1124; 1995). The aim of this study was to compare sevoflurane with isoflurane for rapid mask induction in six dogs sedated by a combination of midazolam (0.1 mg/kg) and butorphanol (0.2 mg/kg). Induction with sevoflurane (5%, 2.4 minimum alveolar concentration [MAC]) in O2 resulted in shorter time to loss of the palpebral reflex, negative tail clamp response, and successful intubation than with isoflurane (3%, 2.4 MAC) in O2. There were no changes in heart rate or mean arterial blood pressure during induction with sevoflurane, whereas an increase in heart rate was observed in dogs induced with isoflurane. A decrease in respiratory rate compared with the pre-induction rate was observed during induction, and associated mild respiratory acidosis, characterized by an increase in arterial PCO2, was measured at the end of the induction period in both induction groups. None of the animals had episodes of induction-related complications. These results suggest that both sevoflurane and isoflurane produce a smooth onset of induction in midazolam and butorphanol-sedated dogs. Sevoflurane is a more suitable for rapid mask induction than isoflurane since it provides faster induction associated with a lower blood/gas partition coefficient.

Anesthesia, Inhalation↗

Lung C-fiber CNS reflex: role in the respiratory consequences of extended environmental tobacco smoke exposure in young guinea pigs.

Environmental tobacco smoke (ETS) exposure harms the respiratory health of children and is associated with an increased risk of asthma and sudden infant death syndrome (SIDS). The mechanisms by which ETS causes these effects are not understood. We hypothesized that one mechanism is an upregulation of the lung C-fiber central nervous system (CNS) reflex responses, which would result in exaggerated reflex responses of apnea, bronchoconstriction, and mucous hypersecretion. The purpose of this work is to highlight evidence obtained in an animal model of postnatal ETS exposure supporting the hypothesis and present data suggesting that actions of the neuropeptide substance P in the nucleus tractus solitarius (NTS) may contribute. Exposing young guinea pigs to sidestream smoke, the surrogate for ETS, for 5 weeks during the equivalent of human childhood, increased the excitability of afferent lung C fibers and NTS neurons in the CNS reflex pathway and prolonged the expiratory apnea. The findings suggest that an increased excitability of NTS neurons that can augment reflex output may contribute to respiratory symptoms in children exposed to ETS. Besides ETS exposure, substance P can also excite NTS neurons and augment lung C-fiber CNS reflex responses. Others have shown that substance P synthesis in lung C fibers is upregulated by another environmental stimulant, allergen. Thus, an upregulation of the substance P system at NTS synapses could contribute to the increased NTS excitability and enhanced reflex responses to lung C-fiber stimulation, providing a potential mechanism to help explain the association of ETS exposure with respiratory symptoms and SIDS.

Animals↗

Respiratory and cardiovascular reflexes elicited by nasal instillation of capsaicin to anesthetized, spontaneously breathing dogs.

Cardiopulmonary reflexes elicited by capsaicin (CAPS) instilled into the nasal passages were determined in 6 anesthetized dogs breathing spontaneously. Nasal instillation of CAPS (10 microg/ml, 10 ml) induced: 1) apneic response characterized by an increase in expiration time; 2) bronchoconstrictor response characterized by an increase in lung resistance and a decrease in dynamic compliance; and 3) cardiovascular response characterized by a decrease in heart rate and an increase in arterial blood pressure. These reflex responses to CAPS were attenuated by pretreatment with a higher dose of CAPS (100 microg/ml, 10 ml), suggesting desensitization of CAPS-sensitive endings. These results suggest that marked cardiopulmonary reflexes are produced by nasal CAPS instillation, which may result, at least in part, from stimulation of nasal CAPS-sensitive sensory afferents.

Administration, Intranasal↗

Effects of nitrous oxide on mask induction of anesthesia with sevoflurane or isoflurane in dogs.

OBJECTIVE: To determine the effects of nitrous oxide (N2O) on the speed and quality of mask induction with sevoflurane or isoflurane in dogs. ANIMALS: 7 healthy Beagles. PROCEDURE: Anesthesia was induced with sevoflurane or isoflurane delivered in 100% oxygen or in a 2:1 mixture of N2O and oxygen via a face mask. Each dog received all treatments with at least 1 week between treatments. Initial vaporizer settings were 0.8% for sevoflurane and 0.5% for isoflurane (0.4 times the minimum alveolar concentration [MAC]). Vaporizer settings were increased by 0.4 MAC at 15-second intervals until settings were 4.8% for sevoflurane and 3.0% for isoflurane (2.4 MAC). Times to onset and cessation of involuntary movements, loss of the palpebral reflex, negative response to tail-clamp stimulation, and endotracheal intubation were recorded, and cardiopulmonary variables were measured. RESULTS: Administration of sevoflurane resulted in a more rapid induction, compared with isoflurane. However, N2O had no effect on induction time for either agent. Heart rate, mean arterial blood pressure, cardiac output, and respiratory rate significantly increased and tidal volume significantly decreased from baseline values immediately after onset of induction in all groups. Again, concomitant administration of N2O had no effect on cardiopulmonary variables. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of N2O did not improve the rate or quality of mask induction with sevoflurane or isoflurane. The benefits provided by N2O attributable to concentrating and second gas effects appear minimal in healthy dogs when low solubility inhalation agents such as isoflurane and sevoflurane are used for mask induction.

Anesthesia, Inhalation↗

Respiratory reflexes in spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane, isoflurane, or halothane.

OBJECTIVE: To characterize respiratory reflexes elicited by nasal administration of sevoflurane (Sevo), isoflurane (Iso), or halothane (Hal) in anesthetized dogs. ANIMALS: 8 healthy Beagles. PROCEDURE: A permanent tracheostomy was created in each dog. Two to 3 weeks later, dogs were anesthetized by IV administration of thiopental and alpha-chloralose. Nasal passages were isolated such that inhalant anesthetics could be administered to the nasal passages while the dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of each anesthetic at 1.2 and 2.4 times the minimum alveolar concentration (MAC) and the full vaporizer setting (5%) were recorded. Reflexes in response to administration of 5% of each anesthetic also were recorded following administration of lidocaine to the nasal passages. RESULTS: Nasal administration of Sevo, Iso, and Hal induced an immediate ventilatory response characterized by a dose-dependent increase in expiratory time and a resulting decrease in expired volume per unit of time. All anesthetics had a significant effect, but for Sevo, the changes were smaller in magnitude. Responses to administration of each anesthetic were attenuated by administration of lidocaine to the nasal passages. CONCLUSIONS AND CLINICAL RELEVANCE: Nasal administration of Sevo at concentrations generally used for mask induction of anesthesia induced milder reflex inhibition of breathing, presumably via afferent neurons in the nasal passages, than that of Iso or Hal. Respiratory reflexes attributable to stimulation of the nasal passages may contribute to speed of onset and could promote a smoother induction with Sevo, compared with Iso or Hal.

Administration, Intranasal↗

[A case of intra-peritoneal recurrence of colon carcinoma that responded remarkably to combined therapy of low-dose leucovorin and 5-fluorouracil].

We treated a patient with intra-peritoneal recurrent tumor from colon cancer who responded completely to chemotherapy of combined low-dose Leucovorin (LV) and 5-fluorouracil (5-FU). The patient was a 75-year-old man. He underwent resection of the transverse colon, sigmoid colon and distal stomach for colon and gastric cancers. Nine months after the operation, his CEA level increased to 39.5 ng/ml and a CT scan revealed an intra-peritoneal tumor measuring about 5 cm. He received chemotherapy of 30 mg/day of LV that was injected in a bolus and 500 mg/day of 5-FU that was given i.v. by continuous infusion for 10 days. At the end of 2 cycles of this regimen, CT scan demonstrated complete tumor remission and the patient's CEA level decreased to normal level. After an additional cycle of this regimen, he received modulated chemotherapy combined with l-Leucovorin and 5-FU as an outpatient. However, after 3 months of treatment, a recurrent tumor was detected in the same portion and the first regimen was re-started for 5 days. After 4 cycles of treatment the tumor disappeared completely from a CT scan. It is important to investigate effective regimens that do not reduce the quality of life of the patient. This clinical experience suggests that a low-dose LV/5-FU therapy may be beneficial to patients with recurrent colon cancer. Further investigation is necessary to establish an effective regimen that can be given for a long period without adverse effects on quality of life.

Aged↗