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Biomedical subjects

A Mizutani

Publications and source records attributed to A Mizutani.

At least 37 records · Page 2Linked to original sources
PubMed1998

Ascorbate-dependent enhancement of nitric oxide formation in activated macrophages.

Macrophages activated with bacterial lipopolysaccharide (LPS) and cytokines produce nitric oxide through the induction of iNOS gene expression. Ascorbate increased NOx (nitrite and nitrate) formation by approximately 40% in a mouse macrophage-like cell line, J774.1, activated with LPS and interferon-gamma. Ascorbate alone exhibited no inductive activity toward NO formation. N(G)-Monomethyl-L-arginine inhibited nitrite formation in cells activated in the presence or absence of ascorbate. Northern and Western blotting analyses showed that both iNOS mRNA and protein steady-state levels were increased approximately twofold in cells activated in the presence of ascorbate compared to in cells activated only with the inducers. These data suggest that ascorbate increased NO production by increasing the amount of iNOS in the activated macrophages.

Animals↗
PubMed1998

Effect of additional general anesthesia with propofol, midazolam or sevoflurane on stress hormone levels in hysterectomy patients, receiving epidural anesthesia.

Hormonal responses after surgery are characterized by increased pituitary-adrenal axis hormones. We undertook this study to determine whether the choice of anesthesia influences stress hormone levels. Twenty-three adult females scheduled for hysterectomy for benign disease under general anesthesia were randomly assigned to one of three groups: epidural/propofol anesthesia (Group P), epidural/midazolam anesthesia (Group M), and epidural/sevoflurane anesthesia (Group S). The concentrations of ACTH and cortisol in group P and group M were significantly less than that of group S at 60 min after the incision. The concentrations of beta-endorphin and aldosterone in group P and group M were significantly less than that of group S at 60 min after the incision and after extubation. We conclude that combined epidural and general anesthesia with propofol or midazolam has a greater suppressive effect than sevoflurane on the stress response of the pituitary-adrenal axis during hysterectomy.

Adrenal Cortex Hormones↗
PubMed1997

Regulation of AP-2-synaptotagmin interaction by inositol high polyphosphates.

The inositol high-polyphosphate series (IHPS) inhibits neurotransmission through binding to the second C2 domain of synaptotagmins I and II(Syt), synaptic vesicle membrane proteins. We have revealed that several proteins, including alpha adaptins which are specific subunits of clathrin assembly protein, AP2, were eluted from mouse brain by affinity elution chromatography from the C2 domains of Syt II-immobilized Sepharose using 50 microM of InsP6. The interaction between Syt II and AP2 was more markedly inhibited by IHPS than by the same concentration of InsP3. Limited digestion of mouse crude synaptosomal fractions with trypsin revealed different cleavage patterns in the presence and absence of 50 microM InsP6. These results suggest that IHPS-binding to the C2B domain of synaptotagmin alters the state of protein-protein interaction including the synaptotagmin-AP2 interaction, possibly resulting in the inhibition of events involved in the synaptic vesicle trafficking.

Adaptor Protein Complex 2↗
PubMed1997

Up-regulation of ganglioside biosynthesis, functional synapse formation, and memory retention by a synthetic ceramide analog (L-PDMP).

To address the role of brain gangliosides in synaptic activity, the ceramide analogs, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) and its enantiomer, L-PDMP, were used to inhibit and stimulate ganglioside biosynthesis in cultured cortical neurons. Prolonged treatment with both PDMP isomers exhibited opposite effects on functional synapse formation measured by spontaneous synchronized oscillatory activity of intracellular Ca2+ between the neurons: suppression by D-PDMP and facilitation by L-PDMP. Up-regulation of synaptic activity by L-PDMP could be correlated with the slow but robust stimulation of ganglioside biosynthesis through activating GM3, GD3 and GQ1b synthases. In a similar time course, the activity of p42 mitogen-activated protein kinase was also enhanced by L-PDMP. To evaluate the efficacy of this drug in long-term memory, rats were trained for 2 weeks using an 8-arm radial maze task, and then forebrain ischemia was induced by 4-vessel occlusion. Treatment with L-PDMP starting 24 hours after the transient ischemia ameliorated the deficit of a well-learned spatial memory, demonstrating the potential therapeutic intervention of the ceramide analog for neurodegenerative disorders.

Animals↗
PubMed1997

Overcoming CPT-11 resistance by using a biscoclaurine alkaloid, cepharanthine, to modulate plasma trans-membrane potential.

Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin, (CPT-11) resistance was overcome by using a biscoclaurine alkaloid, cepharanthine, in CPT-11- and multidrug-resistant 50MT-1 cells. 50MT-1 cells were established from a mouse breast-cancer cell line, FM3A, by subjecting the cells to a low dose of CPT-11 continuously. 50MT-1 cells exhibited resistance to CPT-11 (40-fold in colony-formation assay) and to other drugs such as doxorubicin (11.7-fold) and etoposide (VP-16) (16.8-fold). The plasma trans-membrane potential was lower in 50MT-1 cells than in FM3A cells, although there were no differences in expressions of P-glycoprotein and of DNA topoisomerase-I and -II proteins. The lower membrane potential in 50MT-1 cells was augmented by co-treatment with a non-toxic dose of cepharanthine. CPT-11 resistance in 50MT-1 cells was overcome (5.0- to 1.4-fold, 6-hr exposure) by the co-treatment with cepharanthine through increasing intracellular accumulation of CPT-11. Resistance to doxorubicin and VP-16 was also overcome by cepharanthine treatment (2.5- to 0.69-fold and 4.2- to 1.4-fold respectively). We conclude that the modification of plasma trans-membrane potential by cepharanthine should be effective in overcoming CPT-11 and multidrug resistance in 50MT-1 cells.

Alkaloids↗
PubMed1997

Postsynaptic blockade of inhibitory postsynaptic currents by plasmin in CA1 pyramidal cells of rat hippocampus.

We have shown previously that plasmin facilitated the generation of long-term potentiation (LTP) in CA1 and dentate region of rat hippocampus. In the present study, we investigated the effects of plasmin on postsynaptic currents in CA1 pyramidal neurons of rat hippocampal slices. Plasmin (100 nM) had no effect on NMDA nor on non-NMDA receptor-mediated excitatory postsynaptic currents. However, plasmin significantly decreased GABA(A) receptor-mediated inhibitory postsynaptic currents. This effect of plasmin disappeared when intracellular Ca2+ was strongly chelated with BAPTA. Furthermore, plasmin attenuated the GABA-induced currents in CA1 pyramidal cells. These results suggest that the STP-enhancing effect of plasmin is due to a blockade of postsynaptic GABA(A) responses and that an increase in intracellular Ca2+ by plasmin may be involved in its mechanism.

Animals↗
PubMed1997

Mutants of the phytopathogenic fungus magnaporthe grisea deficient in alternative, cyanide-resistant, respiration

The phytopathogenic fungus Magnaporthe grisea has a cyanide-resistant respiratory pathway. The fungicide SSF-126 ((E)-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl) acetamide) blocks the cytochrome electron transport of M. grisea and induces the alternative respiratory pathway. Twelve mutants of M. grisea more susceptible to SSF-126 than wild type were identified after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. Five mutants retained a reduced alternative respiration activity, and seven mutants lacked alternative pathway activity. A monoclonal antibody against the maize alternative oxidase cross-reacted against a 40-kDa mitochondrial protein of M. grisea, indicating that the 40-kDa protein is an alternative oxidase. Immunoblot analysis indicated that the seven completely deficient mutants grouped into two classes: four mutants produced the 40-kDa proteins while the other three mutants failed to produce the functional protein. Copyright 1997 Academic Press. Copyright 1997 Academic Press

Journal Article↗
PubMed1997

Pharmacological analysis of the inflammatory exudate-induced histamine production in bone marrow cells.

The inflammatory exudate at the post-anaphylaxis phase of allergic inflammation in rats has an ability to enhance histamine production by bone marrow cells. To analyze the mechanism of the inflammatory exudate-induced histamine production pharmacologically, the effects of several drugs were examined in cultures of bone marrow cells. Incubation of the bone marrow cells in the presence of the inflammatory exudate that had been centrifuged and dialyzed against Hanks' balanced salt solution increased histidine decarboxylase activity in the cells and histamine concentration in the conditioned medium. The induction of histamine production by the inflammatory exudate was inhibited by actinomycin D (0.01-1 microM), an inhibitor of RNA synthesis, and cycloheximide (0.1-10 microM), a protein synthesis inhibitor. The protein kinase C inhibitors staurosporine (2-20 nM), K-252a (6-200 nM), and H-7 (10.3-103 microM) also inhibited the inflammatory exudate-induced histamine production in a concentration-dependent manner. The tyrosine kinase inhibitor genistein (3.7-37 microM) also inhibited the inflammatory exudate-induced histamine production, but the protein kinase A inhibitor H-89 (0.2 microM), and the adenylate cyclase activator forskolin (0.1 microM) showed no effect. These findings suggest that histamine production induced by the inflammatory exudate is mediated by the de novo synthesis of histidine decarboxylase and by the activation of protein kinase C and tyrosine kinase.

Anaphylaxis↗
PubMed1997

Ascorbate-dependent expression of ubiquitin genes in guinea pigs.

In an attempt to characterize a gene(s), of which the expression is ascorbate-dependent, a cDNA fragment encoding ubiquitin was isolated from a subtracted cDNA library constructed from spleen RNAs of ascorbate-deficient or -replete guinea pigs. On Northern blot analysis, three transcripts (1.8 kb ubiX, 1.3 kb ubiY and 0.7 kb ubiZ) were detected. The ubiY encodes four direct repeats of the 76 amino acid ubiquitin sequence with seven additional amino acids, V-Y-A-S-P-I-F, at the C-terminus. The transcript ubiX appears to comprise more than five repeats of the ubiquitin-encoding unit. The ubiZ encodes a ubiquitin monomer fused to an 80 amino acid extension exhibiting 100% amino acid sequence identity to the human homolog, HUMUBA80R. The ubiX gene was expressed animal-dependently. The ubiY mRNA levels decreased under ascorbate-deficient conditions, and increased under ascorbate-replete conditions, whereas ubiZ mRNA remained unaltered at low levels under the feeding conditions used here.

Amino Acid Sequence↗
PubMed1997

Antisweet natural products. XII. Structures of sitakisosides XI-XX from Stephanotis lutchuensis Koidz. var. japonica.

From the fresh stem of Stephanotis lutchuensis var. japonica, ten new oleanane-type triterpenoid glycosides, named sitakisosides XI-XX (1-10), were isolated. Their structures were determined on the basis of spectroscopic data and chemical evidence. The results show that all have a 3-O-beta-D-xylopyranosyl(1 --> 6)-beta-D-glucopyranosyl(1 --> 6)- beta-D-glucopyranosyl moiety and the aglycones of sitakisosides XI-XV, XVI and XVII, XVIII and XIX, and XX are sitakisogenin, chichipegenin, marsglobiferin and longispinogenin, respectively. Sitakisosides XI-XIII, XVI and XVIII, having an acyl group, showed antisweet activity.

Carbohydrate Sequence↗
PubMed1997

[Disorders of neuronal migration in cerebral palsy].

We have analyzed 60 autopsy cases of cerebral palsy (CP) at the Aichi Prefectural Colony. The weight of the CP brains was distributed most frequently between 60 to 70% of normal brain weight. Coronal thin sections of the whole brains through the mammillary bodies were made using a large-sized miorotome and stained with hematoxylin-eosin (HE) and Klüver-Barerra (KB) stains. Macroscopically, CP brains were classified into microgyria-pachygyria type (45 cases), thin cerebral mantle type (10 cases), hydrocephalus type (3 cases), and lissencephalic type (2 cases). Macroscopic image analysis was performed using the KB-stained whole brain sections from the microgyria-pachygyria type CP brains, as well as 9 brains of control cases with non-neurological diseases and 4 brains with Fukuyama congenital muscular dystrophy (FCMD). The CP brains showed narrowed white matter with dilated ventricles compared with the controls. Microscopic analysis showed that ectopic grey matter (about 16%), and disorganization of the cerebral cortex (about 50%), and neuronal depletion (about 50%). These findings suggest that some of the CP brains resulted from disturbance of neuronal migration.

Adolescent↗
PubMed1996

Possible involvement of plasmin in long-term potentiation of rat hippocampal slices.

Effects of proteases and protease inhibitors on generation of long-term potentiation (LTP) were investigated in the CA1 and dentate regions of rat hippocampus. Plasmin, a serine protease, and its precursor plasminogen significantly enhanced short-term potentiation (STP) induced by a weak tetanic stimulation, without affecting basal responses. The STP-enhancing effect of plasmin disappeared by concomitant perfusion of alpha 2-antiplasmin, an endogenous plasmin inhibitor. Other proteases, such as thrombin, trypsin and cathepsin B, did not affect STP. On the other hand, alpha 2-antiplasmin and leupeptin significantly attenuated LTP induced by a strong tetanus though plasminogen or plasmin itself did not influence LTP. Furthermore, plasminogen and plasmin did not affect NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. These results suggest that endogenous plasmin is involved in the mechanism of LTP in CA1 and dentate regions of rat hippocampus and that the STP-enhancing effect of plasmin is independent of NMDA receptors.

Animals↗
PubMed1996

Effects of glucosylceramide synthase inhibitor and ganglioside GQ1b on synchronous oscillations of intracellular Ca2+ in cultured cortical neurons.

To evaluate the role of endogenous gangliosides in synapse formation, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to deplete glycosphingolipids (GSLs) of cultured rat cerebral cortical neurons. Synapse formation between the neurons was estimated by the synchronous oscillation of synaptic activity monitored by fura-2 calcium imaging. Treatment with D-PDMP resulted in dose- and time-dependent decreases in the frequency of synchronous oscillations. When a series of gangliosides (GM3, GM1, GD3, GD1b, GT1b, and GQ1b) was supplemented to the GSL depleted cells, only GQ1b was able to normalize the decreased frequency by D-PDMP. These results suggest that de novo synthesis of a particular molecular species of the gangliosides, GQ1b, is essential for synapse formation and synaptic activity.

Animals↗
PubMed1996

[Stress hormone response during midazolam/fentanyl anesthesia combined with epidural anesthesia for abdominal total hysterectomy].

Stress hormone response was investigated during midazolam/fentanyl/oxygen/air anesthesia combined with epidural anesthesia in six patients undergoing abdominal total hysterectomy (group MF). A control group of six patients received nitrous oxide/oxygen/sevoflurane anesthesia combined with epidural anesthesia (group C). We evaluated plasma concentrations of ACTH, cortisol, aldosterone and beta-endorphin during the control period, 10 min, 60 min after incision, and in the recovery room. In group C, plasma concentrations of ACTH, cortisol, aldosterone and beta-endorphin increased significantly 60 min after incision compared with control concentrations. But in group MF, they did not increase significantly during anesthesia. In the recovery room there were significant differences compared with preinduction concentrations in both groups. It is concluded that midazolam/fentanyl anesthesia combined with epidural anesthesia is more effective than nitrous oxide/oxygen/sevoflurane anesthesia combined with epidural anesthesia to control the stress response to surgery.

Adrenocorticotropic Hormone↗
PubMed1996

[IGF-1 levels in elderly patients during perioperative period].

In the present study, concentrations of serum cortisol, ACTH, IRI, growth hormone and insulin-like growth factor 1 (IGF-1) were measured in 24 surgical patients. Patients were divided into two groups, elderly group (n = 12, age > or = 60, mean age: 68.4 +/- 1.3) and younger group (n = 12, age < 60, mean age: 44.5 +/- 3.5). The samples were taken before and immediately after surgery and on days 1 and 2 postoperatively. Serum levels of cortisol, ACTH, IRI and growth hormone increased significantly after surgery compared to baseline values but they showed no significant differences between elderly group and younger group. Only serum IGF-1 levels were significantly different between them. They were at consistently lower levels in elderly group throughout this study. In contrast, they decreased significantly after surgery, but high IGF-1 levels were maintained in younger group. Catabolic condition shown by negative nitrogen balance is induced after surgery. IGF-1 has potential anabolic effect in human. The pharmacological approach using IGF-1 in the elderly surgical patients will be necessary in order to improve their overall conditions before and after surgery in the future.

Adrenocorticotropic Hormone↗
PubMed1995

Purification and characterization of a novel protein activator of Ca2+/calmodulin-dependent protein kinase I.

A protein activator of Ca2+/calmodulin (CaM)-dependent protein kinase I was purified from rat brain. The activator was retained on a CaM-Sepharose column in the presence of Ca2+ and kinase assay of renatured gel revealed the 64 kDa molecule in the purified activator fraction to be autophosphorylated and to phosphorylate recombinant CaM kinase I in the presence of Ca2+/calmodulin. These results suggest that this activator of CaM kinase I is also a CaM-dependent protein kinase. Phosphorylation of CaM kinase I by the activator resulted in drastic potentiation of its CaM-dependent activity. Furthermore, kinetic analyses demonstrated that the activation decreases the Km values of CaM kinase I for both ATP and syntide-2 without a change in Vmax values. Considering the quite low enzymatic activity of recombinant CaM kinase I without activation, the 64 kDa species might be essential for CaM kinase I function in vivo.

Adenosine Triphosphate↗