Biomedical subjects

M Misawa

Publications and source records attributed to M Misawa.

At least 19 recordsLinked to original sources

PubMed2006

Hydration of alcohol clusters in 1-propanol-water mixture studied by quasielastic neutron scattering and an interpretation of anomalous excess partial molar volume.

Quasielastic neutron scattering measurements have been made for 1-propanol-water mixtures in a range of alcohol concentration from 0.0 to 0.167 in mole fraction at 25 degrees C. Fraction alpha of water molecules hydrated to fractal surface of alcohol clusters in 1-propanol-water mixture was obtained as a function of alcohol concentration. Average hydration number N(ws) of 1-propanol molecule is derived from the value of alpha as a function of alcohol concentration. By extrapolating N(ws) to infinite dilution, we obtain values of 12-13 as hydration number of isolated 1-propanol molecule. A simple interpretation of structural origin of anomalous excess partial molar volume of water is proposed and as a result a simple equation for the excess partial molar volume is deduced in terms of alpha. Calculated values of the excess partial molar volumes of water and 1-propanol and the excess molar volume of the mixture are in good agreement with experimental values.

Journal Article↗

PubMed2004

Mass-fractal clustering and power-law decay of cluster size in 1-propanol aqueous solution.

Mesoscale structure of 1-propanol aqueous solutions with propanol mole fraction xp ranging from 0.1 to 0.33 has been studied by means of small angle neutron scattering (SANS) and large-scale reverse Monte Carlo (RMC) technique. Analysis of the SANS intensities in terms of a fractal model shows that the fractal dimension df of mesoscale structure of the solution is about 1.8-1.9 for water-rich solution and about 1.5 for propanol-rich solution. Percolation analysis on the RMC results reveals that the water molecules and the propanol molecules cluster, respectively, as a mass fractal, the dimension dM of which is about 2.3-2.5 for both clusters for water-rich solution. Furthermore, the distribution of the cluster size is expressed by a simple power law with an exponent tau of about 1.35-1.5 for the propanol clusters and 1.05-1.2 for the water clusters. These results imply that the current solution is characterized by polydisperse mass fractals. In fact, a theoretical relation for polydisperse system of mass fractals, df = dM(2-tau), holds well in the current solution. The characteristic change in df from 1.8-1.9 to 1.5 described above is attributed to the crossover between the water-rich regime and the propanol-rich regime. Most of the water molecules and the propanol molecules are located on the interface between clusters, and the water molecules form thin layers of about 10 A thick irrespective of 1-propanol content studied.

Journal Article↗

PubMed2004

Hyperresponsiveness of bronchial but not tracheal smooth muscle in a murine model of allergic bronchial asthma.

OBJECTIVE: To determine a change in airway smooth muscle contractility in a murine model of allergic asthma, the responsiveness of airway smooth muscles isolated from ovalbumin (OA)-sensitized and -challenged mice was compared with that from control animals. METHODS: Actively sensitized mice were repeatedly challenged by ovalbumin (OA) antigen inhalation. Twenty-four h after the last antigen challenge, tracheal and bronchial smooth muscle responsiveness to acetylcholine (ACh) and endothelin-1 (ET-1) were measured. Airway microvascular leakage and histochemistry were also determined as indices of airway inflammation. RESULTS: Both the ACh and ET-1 responsiveness of bronchial, but not tracheal, smooth muscles were significantly augmented in OA-challenged mice, whereas no significant change in the expression levels of M2, M3 and ETB receptors was observed. The Evans blue dye extravasation in the main bronchial, but not tracheal, tissue of OA-challenged mice was significantly increased as compared with that of sensitized control animals. A marked inflammatory cells infiltration was also observed in bronchial but not tracheal tissues of OA-challenged mice. CONCLUSION: Repeated antigen challenge to sensitized mice caused a hyperresponsiveness of bronchial, but not tracheal, smooth muscle accompanied with bronchial tissue inflammation.

Acetylcholine↗

PubMed2004

GABAA receptor-mediated inhibition by ethanol of long-term potentiation in the basolateral amygdala-dentate gyrus pathway in vivo.

Although ethanol has been reported to inhibit the induction of long-term potentiation in hippocampal CA1 and dentate gyrus synapses of rats, very little is known about the effect of ethanol on synaptic plasticity in other brain regions. Therefore, in the present study, we investigated the effect of ethanol on long-term potentiation in synaptic pathway from the basolateral amygdala to the dentate gyrus by using anesthetized rats in vivo. I.v. (20-40% x 2 ml/kg) or i.c.v. (30-40% x 5 microl) administration of ethanol did not affect the basal amplitude of dentate gyrus field potential evoked by basolateral amygdala stimulation, but significantly inhibited the induction of long-term potentiation following application of tetanic stimulation. Since long-term potentiation in this pathway was independent of N-methyl-d-aspartate receptors, the inhibitory effect of ethanol is unlikely to be caused by suppression of N-methyl-d-aspartate receptor function. Alternatively, long-term potentiation in this pathway was significantly suppressed by the benzodiazepine agonist diazepam (2 mg/kg, i.p.), and the inhibitory effect of ethanol was abolished by the GABAA receptor channel blocker picrotoxin (1 mg/kg, i.p.). The present study demonstrates that ethanol inhibits the induction of long-term potentiation in the basolateral amygdala-dentate gyrus pathway by enhancing GABAA receptor-mediated neurotransmission.

Amygdala↗

PubMed2002

Long-term outcome after allogeneic bone marrow transplantation for hematological malignancies with non-remission status. Results of a single-center study of 24 patients.

To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.

Adolescent↗

PubMed2001

Effects of Y-27632 on acetylcholine-induced contraction of intact and permeabilized intrapulmonary bronchial smooth muscles in rats.

In the present study, the effects of a selective Rho-associated coiled-coil forming protein kinase (ROCK) inhibitor, Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-(4-pyridyl)cyclohexanecarboxamide dihydrochloride] on acetylcholine-induced contraction and Ca(2+) sensitization of rat bronchial smooth muscle were examined. Intact and beta-escin-permeabilized muscles of the third branch of intrapulmonary bronchi were used. In intact muscles, Y-27632 (10(-6)-10(-4) M) concentration-dependently inhibited acetylcholine-induced contractile responses. In acetylcholine (10(-3) M)-precontracted intact muscles, the maximal relaxation (about 50% inhibition of contraction) was obtained by a concentration of 10(-4) M Y-27632, which had no effect on the resting tone. In beta-escin-permeabilized muscles, addition of acetylcholine (10(-5)-10(-3) M) plus GTP (100 microM) induced a further contraction, i.e., Ca(2+) sensitization at a constant Ca(2+) concentration of pCa=6.0. The acetylcholine-induced Ca(2+) sensitization was completely blocked in the presence of 10(-4) M Y-27632, whereas the Ca(2+)-induced contraction itself was not affected by Y-27632. Immunoblot study revealed the expression of ROCK-I and ROCK-II proteins in the intrapulmonary bronchi of rats. These findings suggest that Y-27632 dilates acetylcholine-mediated contraction of rat bronchial smooth muscle by inhibiting RhoA/ROCK-mediated Ca(2+) sensitization.

Acetylcholine↗

PubMed2001

Possible involvement of G(i3) protein in augmented contraction of bronchial smooth muscle from antigen-induced airway hyperresponsive rats.

To investigate a possible involvement of pertussis toxin (PTX)-sensitive heterotrimeric G proteins in the pathogenesis of airway hyperresponsiveness, the effect of PTX treatment on the augmented contractile response to acetylcholine (ACh) in bronchial smooth muscle of antigen-induced airway hyperresponsive rats was determined. In bronchial smooth muscle of airway hyperresponsive rats that were actively sensitized and repeatedly challenged with 2,4-dinitrophenylated Ascaris suum antigen, ACh-induced contractions were markedly augmented. The augmented contractile responses in the airway hyperresponsive group were significantly inhibited after treatment with PTX (1 microg/mL for 6 hr, 37 degrees ), whereas only a slight attenuation was observed in the normal control group. The level of G(alpha)i3 (measured by immunoblotting), but not other alpha-subunits of G(i/o) family proteins, in bronchial smooth muscle of the airway hyperresponsive rats was significantly increased as compared with that of control animals. It is concluded that PTX-sensitive muscarinic contractile responses of bronchial smooth muscle might be augmented upon antigen-induced airway hyperresponsiveness in rats, probably due to an up-regulation of G(alpha)i3 protein of bronchial smooth muscle.

Acetylcholine↗

PubMed2001

Site difference in RhoA expression between rat bronchial and tracheal smooth muscles after antigen challenge--relation to development of hyperresponsiveness.

OBJECTIVE: The present study compared the effects of repeated antigen exposure on the development of hyperresponsiveness and the expression of RhoA in the main bronchial and lower tracheal smooth muscles of sensitized METHODS: Actively sensitized rats were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge the isometrical contractions of the bronchial and tracheal smooth muscles were measured. Immunoblottings were also performed using bronchial and tracheal homogenates and the density ratios of RhoA/beta-actin were calculated to quantify the levels of RhoA. RESULTS: Acetylcholine-induced contraction of bronchial, but not tracheal, smooth muscle of antigen-treated rats was significantly augmented as compared with that of control rats, indicating that airway hyperresponsiveness appeared by antigen challenge in bronchial smooth muscle. RhoA expression in bronchial, but not tracheal, smooth muscle was significantly increased in the antigen-treated animals. CONCLUSION: The increased expression of RhoA is suggested to have an important role in developing hyperresponsiveness of bronchial smooth muscle.

Acetylcholine↗

PubMed2001

Increased expression of G12 and G13 proteins in bronchial smooth muscle of airway hyperresponsive rats.

OBJECTIVE: To obtain information on the activation pathway of the monomeric G protein, RhoA, in bronchial smooth muscle, the expression of G alpha12 and G alpha13 in bronchial smooth muscle of the rat was determined. The levels of these G proteins were also compared between antigen-induced airway hyperresponsive and normal control groups. METHODS: Actively sensitized rats were repeatedly challenged by antigen inhalation. Twenty-four hours after the final antigen challenge, membrane preparations of bronchial smooth muscles were prepared. Immunoblottings were performed, and the density ratios of G alpha12/beta-actin and G alpha13/beta-actin were calculated to quantify the levels of these G-protein alpha subunits. RESULTS: Both G alpha12 and G alpha13 proteins were expressed in rat bronchial smooth muscle. The levels of bronchial G alpha12 and G alpha13 proteins in the repeatedly antigen challenged rats were significantly increased as compared with those in control animals; the magnitude of upregulation in the airway-hyperresponsive group was 89% and 68% in the control group, respectively. CONCLUSION: G alpha12 and G alpha13 proteins were expressed in rat bronchial smooth muscle. Considering the probable involvement of G12 and G13 proteins in Ca2+ sensitization through Rho protein, the augmented expression of such G proteins after repeated antigen challenge may be responsible for the hyperresponsiveness of bronchial smooth muscle contraction in rats.

Animals↗

PubMed2001

CT findings of descending necrotising mediastinitis via the carotid space ('Lincoln Highway').

A 3-year-old girl with fever and neck swelling showed widening of the superior mediastinum on chest radiographs. Contrast-enhanced CT of the neck revealed ill-defined low-attenuation areas with a thick, enhanced rim adjacent to the hypertrophied palatine tonsil. The abscess extended inferiorly within the carotid sheath between the carotid artery and the internal jugular vein into the anterior mediastinum. The carotid space is considered an important conduit of descending necrotising mediastinitis and is called the 'Lincoln Highway' as previously suggested.

Carotid Arteries↗

PubMed2001

Augmented acetylcholine-induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats.

Acetylcholine (ACh)-induced translocation of RhoA in bronchial smooth muscle of repeatedly antigen-challenged rats that have a marked airway hyperresponsiveness (AHR) was examined. ACh induced time- and concentration-dependent translocation of RhoA to the plasma membrane, indicating an activation of RhoA in bronchial smooth muscle. The level of ACh-induced RhoA translocation was further increased markedly in the AHR group as compared to that in the control group. It is suggested that the augmented activation of RhoA observed in the hyperresponsive bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+) sensitization of bronchial smooth muscle contraction associated with AHR.

Acetylcholine↗

PubMed2001

[Intestinal permeability in Crohn's disease and effects of elemental dietary therapy].

Enteral intake of non-metabolic monosacharide and disaccharide, followed by measurement of the urinary excretion ratio of the two, is a method used to investigate intestinal permeability. L/R ratio (lactulose/1-rhamnose urinary excretion ratio) is considered an indicator of permeability of the small intestine. An increased L/R ratio is caused by mucosal disorders of the small intestine. The L/R ratio in all patients (n = 92) with Crohn's disease was 0.079 +/- 0.081 (mean +/- S.D.), which was significantly higher than the value in normal controls (0.027 +/- 0.009, n = 20, p < 0.05). In 39 patients with Crohn's disease, we assessed intestinal permeability before after treatment with an elemental diet, and during remission. The L/R ratio was 0.120 +/- 0.092, before treatment and 0.065 +/- 0.097 after treatment (p < 0.05), showing increased intestinal permeability before elemental dietary treatment. During remission, the L/R ratio was 0.035 +/- 0.028; this did not differ significantly from the value obtained after treatment. We conclude that intestinal permeability is useful for investigating disease activity in patients with Crohn's disease.

Adolescent↗

PubMed2000

Effects of the non-competitive NMDA receptor antagonist ketamine on morphine-induced place preference in mice.

The effects of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, on morphine-induced place preference were examined in mice. Morphine (1-5 mg/kg, s.c.) produced a dose-related place preference in mice. Ketamine alone (3, 10 mg/kg, i.p.), like dizocilpine alone (0.2 mg/ kg, i.p.), also produced a preference for the drug-associated place. Pretreatment with ketamine (10 mg/ kg, i.p.) or dizocilpine (0.1 and 0.2 mg/kg, i.p) suppressed the place preference produced by morphine in a dose-dependent manner. These findings provide the first demonstration that ketamine alone produces a place preference using the conditioned place preference (CPP) paradigm, but that mice treated with ketamine combined with morphine show neither a morphine- nor a ketamine-induced place preference.

Analgesics, Opioid↗

PubMed2000

Effects of differential modulation of mu-, delta- and kappa-opioid systems on bicuculline-induced convulsions in the mouse.

The present study investigated the effects of micro-, delta- and kappa-opioid receptor agonists on seizures produced by blockade of gamma-aminobutyric acid (GABA)-mediated synaptic transmission in the mouse. The selective GABA(A) receptor antagonist bicuculline (1.25-3 mg/kg) given subcutaneously caused dose-dependent clonic-tonic convulsions. These convulsions were potentiated by the prototypic mu-opioid receptor agonist morphine given subcutaneously 20 min prior to a subconvulsive dose of bicuculline. The potentiation by morphine was completely reversed by pretreatment intraventricularly with the selective mu-opioid receptor antagonist beta-funaltrexamine (0.5 microgram/mouse). Pretreatment intraventricularly with the selective delta-opioid receptor agonists 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12, 12abeta-octahydro-quinolino[2,3,3-g]isoquinoline ((-)TAN-67) or [D-Pen(2,5)]-enkephalin (DPDPE) showed a dose-dependent increase in the incidence of convulsions. Pretreatment with naltrindole (2 mg/kg, s.c.), a selective delta-opioid receptor antagonist, abolished the enhancement of the bicuculline-induced convulsions by DPDPE. In contrast, pretreatment with the selective kappa-opioid receptor agonist U-50,488H (0.6-80 mg/kg, subcutaneously or 25-100 microgram/mouse, intraventricularly) produced a dose-dependent suppression of the bicuculline-induced convulsions. The inhibitory effect of U-50,488H was completely blocked by pretreatment subcutaneously with nor-binaltorphimine (5 mg/kg), a selective kappa-opioid receptor antagonist. This study demonstrates that activation of both mu- and delta-opioid receptors increases the incidence of convulsions produced by blockade of GABA-mediated synaptic transmission, while stimulation of kappa-opioid receptors has an anticonvulsive effect.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2000

Gq protein level increases concurrently with antigen-induced airway hyperresponsiveness in rats.

In the present study, bronchial Gq protein level of the airway hyperresponsive rats was determined by using immunoblot analysis. In the airway hyperresponsive rats that were sensitized and repeatedly antigen challenged, the in vitro bronchial responsiveness to acetylcholine was significantly enhanced as compared with that in the sensitized control group. Moreover, the bronchial contraction induced by 10 microM AlF(4)(-) (generated by 10 microM AlCl(3) plus 10 mM NaF) was significantly elevated after repeated antigen challenge (0.44+/-0.13 and 1.09+/-0.09 g tension in the control and airway hyperresponsive groups, respectively; P<0.01). In both groups, immunoblotting with the antibody against G alpha q gave a single 42 kD band. The G alpha q protein levels in the airway hyperresponsive group (0.58+/-0.12) estimated by G alpha q/beta-actin ratio was significantly greater than those in the control group (0.30+/-0.10; P<0.05). These findings suggest that the increase in G alpha q protein level may be involved in the pathogenesis of antigen-induced airway hyperresponsiveness in rats.

Animals↗

PubMed2000

Ethanol, but not the anxiolytic drugs buspirone and diazepam, produces a conditioned place preference in rats exposed to conditioned fear stress.

The present study was designed to investigate the role of an anxiolytic effect in the development of a drug-associated place preference in rats exposed to conditioned fear stress, using the conditioned place-preference paradigm. The administration of a low dose of ethanol (300 mg/kg, IP) and the anxiolytic drugs, buspirone (1 and 2 mg/kg, IP) and diazepam (1.25 and 2.5 mg/kg, IP), did not produce a place preference in rats that were not exposed to conditioned fear stress. In rats that were exposed to conditioned fear stress, ethanol produced a significant place preference, while buspirone and diazepam failed to produce a place preference. In addition, ethanol, buspirone, and diazepam produced no place preference in rats treated with an anxiogenic dose of pentylenetetrazole (20 mg/kg, IP). A significant decrease in locomotor activity was observed in rats exposed to conditioned fear stress. Ethanol, but not buspirone and diazepam, significantly recovered or increased locomotor activity in rats exposed to conditioned fear stress. Further, the locomotor-stimulating effect of ethanol was markedly enhanced by repeated exposure to conditioned fear stress. These results suggest that the stimulating effect may be strongly related to the development of the rewarding effect of a low dose of ethanol under psychological stress, and that the conditioned place preference paradigm with conditioned fear stress may be useful for studying the rewarding mechanism of ethanol with regard to the interaction between ethanol and psychological stress.

Animals↗

PubMed2000

[Proposals for innovative pharmacology education from the perspective of several fields--in response to rapidly changing times].

The Japanese Pharmacological Society has not given a symposium to discuss the topic of overall pharmacology education since 1994 (the 67th Annual Meeting). Thereafter, we have been witnessing great changes in the environment surrounding pharmacology, where scientific advances in life science have made boundaries between the various life sciences ambiguous and have brought the following questions before us: what is pharmacology and what should it be? Considering the situation, the Committee of Education of the Society organized a symposium on pharmacology education at the 73rd Annual Meeting in 2000, which will discuss current problems encountered in pharmacology education today and what pharmacology education should be hereafter. The symposists consisted of five people with backgrounds in basic medicine (biochemistry), clinical medicine (internal medicine), hospital pharmacy, pharmaceutical industry and administration (the Ministry of Health and Welfare). They unanimously emphasized that education of pharmacology should be reformed profoundly so as to contribute to a greater degree to professional medical services and new drug development as well as to basic science and meet the needs of the new era. We hope this symposium will trigger a further discussion on pharmacology education for the future.

Drug Industry↗

PubMed2000

Acetylcholine-induced smooth muscle contraction of intrapulmonary small bronchi is augmented in antigen-induced airway hyperresponsive rats.

Smooth muscle responsiveness of intrapulmonary small bronchi obtained from repeatedly antigen-challenged rats was compared with that from control animals to determine whether smooth muscle contractility of peripheral airways is augmented by such repeated challenge. In intact (non-permeabilized) smooth muscles of intrapulmonary bronchi, the acetylcholine (ACh)-induced contractile response was significantly augmented in the repeated challenge group, although 60-mM K+-induced contraction was within the normal level. In beta-escin-permeabilized muscles, no significant difference between groups was observed in the Ca2+-induced contractile responses. Thus, augmented ACh-induced contraction of intact intrapulmonary small bronchial smooth muscle might be, at least in part, due to an enhanced ACh-mediated Ca2+-sensitizing signal.

Acetylcholine↗