[Gamma radiosurgery for malignant tumors].
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Adolescent↗
Biomedical subjects
M Niwa
Publications and source records attributed to M Niwa.
GABAB receptor antagonist CGP 35348 shortens transcallosal response latency of pyramidal tract neurons.
The effects of a specific GABAB receptor antagonist, p-(3-aminopropyl)-p-diethoxymethyl-phosphonic acid (CGP 35348), on pyramidal tract neuron responses to transcallosal stimulation were investigated in the cat motor cortex in vivo. Iontophoretic application of CGP 35348 significantly increased the number of spikes from 10.3 +/- 4.4 (control; n = 27; mean +/- S.D.) to 16.7 +/- 7.2 (CGP 35348) for 20 transcallosal stimulation trials, while the latency of neuronal activity was significantly shortened from 4.4 +/- 2.1 ms (control; n = 27; mean +/- S.D.) to 3.8 +/- 1.7 ms (CGP 35348). In conclusion, CGP 35348 facilitated transcallosal synaptic transmission between pyramidal tract neurons by removal of GABAB inhibition.
Action Potentials↗
High-level production, chemical modification and site-directed mutagenesis of a cephalosporin C acylase from Pseudomonas strain N176.
A cephalosporin acylase from Pseudomonas strain N176 hydrolyses both 7-beta-(4-carboxybutanamido)-cephalosporanic acid (glutarylcephalosporanic acid) and cephalosporin C to 7-amino-cephalosporanic acid. However, its productivity in the original host was low and its activity against cephalosporin C was not sufficient for direct large-scale production of 7-amino-cephalosporanic acid. In order to overcome these problems, we established a high-level expression system for the acylase in Escherichia coli. Tyr270 in the acylase is reported to play an important role in the interaction with glutarylcephalosporanic acid, as determined from the reaction with an affinity-label reagent, 7 beta-(6-bromohexanoylamido) cephalosporanic acid [Ishii, Y., Saito, Y., Sasaki, H., Uchiyama, F., Hayashi, M., Nakamura, S. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 598-603] and modification with tetranitromethane [Nobbs, T. J., Ishii, Y., Fujimura, T., Saito, Y. & Niwa, M. (1994) J. Ferment. Bioeng. 77, 604-609]. From carbamoylation with potassium cyanate and site-directed point mutagenesis of the cephalosporin C acylase, we have deduced that Tyr270 exists at a position where it can interact with a residue (possibly Ser239) corresponding to inactivation by carbamoylation. We mutated Met269 and Ala271 of the acylase and found that mutation of Met269 to Tyr or Phe caused a 1.6-fold and 1.7-fold increase, respectively, of specific activity against cephalosporin C as compared to that of the wild-type enzyme. Kinetic studies of these mutants revealed that their kcat values increased, although their Km values against cephalosporin C were not changed. These data indicate that the mutation of Met269 near Tyr270 induces a minor conformational change to increase the stability of the activated complex with the enzyme and cephalosporin C. In particular, a mutant in which Met269 was replaced by Tyr was 2.5-fold more efficient in converting cephalosporin C to 7-amino-cephalosporanic acid than the wild-type enzyme under conditions similar to those in a bio-reactor system.
Amino Acid Sequence↗
Differential mechanism of peptide YY and neuropeptide Y in inhibiting motility of guinea-pig colon.
The effect of peptide YY on contractility, acetylcholine release and noradrenaline release was examined in the isolated guinea-pig colon, and findings were compared with those for neuropeptide Y. Peptide YY and neuropeptide Y inhibited the twitch contractions mediated by the stimulation of cholinergic neurons. Peptide YY, neuropeptide Y, [Leu31,Pro34]neuropeptide Y and neuropeptide Y-(13-36) inhibited the electrically stimulated release of acetylcholine. Neuropeptide Y, but not peptide YY, inhibited the high K(+)-stimulated tetrodotoxin-resistant release of acetylcholine, while the inhibitory effect of neuropeptide Y disappeared after treatment with yohimbine. Neuropeptide Y, but not peptide YY or neuropeptide Y analogues, evoked the release of noradrenaline. After desensitization to the effects of neuropeptide Y, peptide YY inhibited electrically stimulated acetylcholine release. Thus, peptide YY inhibits acetylcholine release through stimulation of a receptor, distinct from the site of action of neuropeptide Y, located on cholinergic neurons as well as the neuropeptide Y Y1 and Y2 receptors in the guinea-pig colon. Neuropeptide Y inhibits acetylcholine release due to the noradrenaline release mediated by stimulation of a receptor distinct from neuropeptide Y Y1 and Y2 receptors, located on adrenergic neurons.
Acetylcholine↗
Contribution of L-type Ca2+ channels to long-term enhancement of high K(+)-evoked release of dopamine from rat striatal slices.
Pre-treatment with BAY K 8644, an L-type voltage-gated Ca2+ channels agonist, produced long-term enhancement (LTE) of over 2 h of high K(+)-evoked dopamine release from rat striatal slices. Exposure to BAY K 8644 under Ca(2+)-free conditions did not enhance this release. Thus, a transient activation of L-type voltage-gated Ca2+ channels followed by Ca2+ entry can trigger LTE of the evoked DA release from striatal tissues. This type of LTE in the striatum underlines the importance of presynaptic mechanisms, including L-type voltage-gated Ca2+ channels of 'long-term potentiation' expression.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Temporal profile of nuclear DNA fragmentation in situ in gerbil hippocampus following transient forebrain ischemia.
To determine the time course of nuclear DNA damage in the gerbil hippocampus following transient ischemia, brain sections 48, 72, 96 h and 7 days following 5 min ischemia were evaluated by a specific in situ labeling method of DNA breaks. After 72 h, only the neurons located in the medial part of the CA1 sector were labeled. And then, DNA damage extended to the lateral part of the sector with time.
Animals↗
NMDA receptor involvement in endothelin neurotoxicity in rat striatal slices.
The high K(+)-evoked dopamine release from rat striatal slices remained impaired by 50% up to 2 h after pulse exposure of the tissues to endothelin-3, under conditions of hypoglycemia/hypoxia. This striatal dysfunction was significantly improved by D-2-amino-5-phosphonopentanoic acid, a NMDA receptor antagonist, at a much lower concentration than that providing protection against NMDA-evoked dysfunction. In light of these findings, the important role of glutamatergic mechanisms, especially NMDA receptors, in mediating endothelin neurotoxicity warrants further attention.
2-Amino-5-phosphonovalerate↗
Heterogeneity of circulating and exudated polymorphonuclear leukocytes in superoxide-generating response to cyclic AMP and cyclic AMP-elevating agents. Investigation of the underlying mechanism.
It has been found that cyclic AMP and cyclic AMP-elevating agents inhibit formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated superoxide production from polymorphonuclear leukocytes (PMNs). The quantitative differences of this inhibitory effect on human and rabbit blood versus human salivary and rabbit peritoneal (tissue) PMNs were investigated. PMNs from all sources showed the same pattern of fMLP-stimulated superoxide generation, although it was slightly higher in tissue PMNs. However, treatment with salbutamol differentially blunted fMLP-stimulated superoxide production from blood PMNs compared with tissue PMNs in both human and rabbit. While it could inhibit production from blood PMNs by 30-60%, it had only a negligible effect on generation from tissue PMNs. Similarly, forskolin, phosphodiesterase IV inhibitor Ro-201724, and dibutryl cyclic AMP showed significantly higher inhibitory effects on superoxide generation from blood PMNs than tissue PMNs in both species. beta-Adrenergic receptors, cyclic AMP accumulation, and protein kinase A activity were investigated in blood versus tissue PMNs to clarify the mechanism underlying the above-mentioned differences. At the beta-adrenergic receptor level, no significant changes were detected in the number or the binding affinity of the receptors in tissue versus blood PMNs of human and rabbit. On the other hand, cyclic AMP accumulation was significantly higher in response to salbutamol and Ro-201724 in fMLP-stimulated blood versus tissue PMNs in human and rabbit. At the same time, blood PMNs showed significantly higher cyclic AMP-dependent protein kinase A activity than tissue PMNs in human and rabbit. We concluded that tissue PMNs are less responsive to the effect of cyclic AMP-elevating agents in terms of fMLP-stimulated superoxide inhibition. This is due to differences, at least, at two levels. The first is lower accumulation of cyclic AMP and the second is lower protein kinase A activity in tissue versus blood PMNs.
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
Endothelin receptor in microvessels isolated from human meningiomas: quantification with radioluminography.
1. We characterized specific 125I-endothelin-1 (125I-ET-1) binding sites in microvessels isolated from human meningiomas, using an in vitro quantitative receptor autoradiographic technique coupled to a radioluminographic imaging plate system. 2. This newly developed and highly sensitive method revealed high-affinity ET receptors present in pellet sections of the microvessels from all the meningiomas studied, regardless of histological subtypes (dissociation constant, 1.2 +/- 0.3 nM; maximum binding capacity, 185 +/- 56 fmol/mg; means +/- SE for nine tumors). 3. In five cases of meningiomas, ET-3 competed for 125I-ET-1 binding to microvessels from those tumors with a low affinity [50% inhibiting concentration (IC50) of 1.6 +/- 0.4 x 10(-6) M], and a selective ETB receptor agonist, sarafotoxin S6c, up to 10(-6) M, did not displace ET binding from the sections. 4. In the sections of microvessels from four other tumors, biphasic competition curves were obtained in the case of incubation in the presence of increasing concentrations of ET-3, with an IC50 of 1.1 +/- 0.2 x 10(-9) M for the high-affinity component and 1.6 +/- 0.3 x 10(-6) M for the low-affinity component, respectively. In addition, S6c competed for ET binding to those sections (IC50 = 2.3 +/- 0.2 x 10(-10) M) and 10(-6) M S6c displaced 30% of the control, corresponding to the high-affinity component of competition curves obtained in the presence of ET-3. 5. Our results suggest that (a) capillaries in human meningiomas express a large number of high-affinity ETA (non-ETB) receptors with a small proportion of ETB receptors, and (b) ET may have a role in neovascularization, tumor blood flow, and/or function of the blood-tumor barrier in meningioma tissues by interacting with specific receptors present on the surface of the endothelium.
Adolescent↗
Time course of nitric oxide synthase activity in neuronal, glial, and endothelial cells of rat striatum following focal cerebral ischemia.
1. The time course of nitric oxide synthase (NOS) activity in neuronal, endothelial, and glial cells in the rat striatum after middle cerebral artery (MCA) occlusion and reperfusion was examined using a histochemical NADPH-diaphorase staining method. 2. In sham-operated rats, neuronal cells of the striatum exhibited strong NADPH-diaphorase activities. When rats were subjected to MCA occlusion for 1 hr, neuronal damage, including neurons with positive NADPH-diaphorase activities, appeared in the striatum at 3 hr after and extended to all areas of the striatum 3-4 days after reperfusion. 3. NADPH-diaphorase activities in the endothelial cells increased in the damaged part of striatum from 3 hr after, peaked at 1-2 days after MCA occlusion/reperfusion, then gradually decreased. 4. In parallel with the development of neuronal damage, some astrocytes and a high proportion of microglia/macrophages located in the perisite and in the center of the damaged striatum, respectively, exhibited a moderate to high level of NADPH-diaphorase activities. Most of these activities disappeared at 4 days after MCA occlusion. 5. These findings provided evidence that an inappropriate activation of NOS in endothelial cells and microglia/macrophages, in response to MCA occlusion/reperfusion, is closely associated with initiation and progression of ischemic neuronal injury in the striatum.
Animals↗
Ibudilast, an anti-allergic and cerebral vasodilator, modulates superoxide production in human neutrophils.
We evaluated the effect of ibudilast on superoxide generation in human neutrophils by chemiluminescence development using luciferine analog, FCLA. By incubating neutrophils with ibudilast (2-200 microM) for more than 10 minutes, fMLP- or PMA-induced chemiluminescence was enhanced. However, the fMLP-induced chemiluminescence was suppressed by incubation for less than 10 minutes. This suppressed effect was missing with PMA-induced chemiluminescence. On the both fMLP- and PMA-induced chemiluminescence, the priming effect of ibudilast was further enhanced by the treatment with H-7, a protein kinase C inhibitor. In contrast, the priming effect of ibudilast on the fMLP-induced chemiluminescence was abolished by the treatment with ST-638, a selective inhibitor of tyrosine kinase. Ibudilast showed a transient stimulatory effect on cyclic AMP accumulation which continued for only a few minutes. Ibudilast showed no significant effect on phospholipase D dependent chemiluminescence, 1,4,5 trisphosphate level, or protein kinase C activity. Ibudilast inhibited extracellular calcium influx. These results suggest that ibudilast acts on or through tyrosine kinase to achieved its priming effect on the fMLP-induced chemiluminescence. The early and transient increase in cyclic AMP level may explain the inhibitory effect of ibudilast on the fMLP-induced chemiluminescence after short time of incubation.
Calcium↗
Opioid receptor interaction and adenylyl cyclase inhibition of dihydroetorphine: direct comparison with etorphine.
To find out the reason of weak addiction property of dihydroetorphine, we compared the affinities of dihydroetorphine to the type selective opioid receptor and inhibition effect on the adenylyl cyclase activity with those of etorphine. Dihydroetorphine and etorphine have almost the same binding affinities to all types (mu, delta, and kappa) of opioid receptors and antagonist binding sites, and have similar inhibition activities to forskolin stimulated adenylyl cyclase. However, dihydroetorphine showed significantly smaller value of DTNB-index compared with that of etorphine. This differentiation may explain partly the high analgesic with low dependence properties of dihydroetorphine.
Adenylyl Cyclase Inhibitors↗
Glial endothelin/nitric oxide system participates in hippocampus CA1 neuronal death of SHRSP following transient forebrain ischaemia.
1. When delayed neuronal death occurred in the hippocampus CA1 pyramidal cell layer of stroke-prone spontaneously hypertensive rats (SHRSP) at 4 and 7 days after a 10 min bilateral carotid occlusion and reperfusion, intense endothelin-1 (ET-1)- and ET-3-like immunoreactivities became evident in astrocytes in the damaged hippocampus CA1 subfields. 2. We also observed that microglia equipped with an ETB receptor aggregated within the CA1 pyramidal cell layer with neuronal death. 3. There was a dramatic increase in nitric oxide synthase (NOS) activity in astrocytes and microglia in the damaged hippocampus CA1 subfields. 4. Thus, the possibility that microglia with the ETB receptor are activated to produce NO, a neurotoxic factor, by astrocytic ET-1 and ET-3 produced in response to transient forebrain ischaemia would have to be considered.
Animals↗
Effects of (-)-epigallocatechin-3-O-gallate (green tea tannin) on the life span of stroke-prone spontaneously hypertensive rats.
1. Effect of (-)-epigallocatechin-3-O-gallate (EGCG), a condensed tannin isolated from green tea leaves, on the life span and hypertensive lesions in the stroke-prone spontaneously hypertensive rat (SHRSP) was compared with that of persimmon tannin. 2. Long-term administration of either 0.5% EGCG or 0.5% persimmon tannin to SHRSP inhibited the incidence of stroke and prolonged the life span, but did not affect the blood pressure. 3. These results indicate that EGCG may prevent incidence of stroke due to the radical scavenging action and inhibition of lipid peroxidation, and may result in prolonging the life span of SHRSP, as in the case of persimmon tannin.
Animals↗
Histological evidence for neuroprotective action of nebracetam on ischemic neuronal injury in the hippocampus of stroke-prone spontaneously hypertensive rats.
The protective effect of nebracetam on ischemic neuronal damage was histologically examined in the pyramidal cell layer of the hippocampal CA1 subfield 7 days after operation using stroke-prone spontaneously hypertensive rats (SHRSP) subjected to 10-min bilateral carotid occlusion. Nebracetam (50 and 100 mg/kg), given orally 10 min after reperfusion, dose-dependently protected against ischemic delayed neuronal damage in the SHRSP with occlusion; however, the blood pressure remained unchanged following nebracetam administration. These findings further support the notion that nebracetam protects against ischemic delayed neuronal cell death in the hippocampus.
Animals↗
Hemifacial spasm in Albright's hereditary osteodystrophy with pseudopseudohypoparathyroidism and nephrogenic diabetes insipidus--case report.
A 30-year-old male with Albright's hereditary osteodystrophy, pseudopseudohypoparathyroidism, and nephrogenic diabetes insipidus presented with hemifacial spasm persisting for 2 years. This association is extremely unusual. Angiography revealed markedly tortuous carotid and vertebral arteries inconsistent with his age. Neurovascular decompression of the left vertebral artery achieved only partial resolution of the spasm.
Adult↗
Subarachnoid hemorrhage of unknown origin associated with Weber-Christian disease--case report.
A 58-year-old female, who had suffered from Weber-Christian disease for 26 years, presented with subarachnoid hemorrhage. Cerebral angiography showed dilatation of the basilar tip. An operation was performed in the chronic stage. The wall of dilated basilar artery was tough, but that of the right superior cerebellar artery was very thin and three small aneurysms were found on the right middle cerebral artery. Blood levels of fibrin degradation products, plasmin-alpha 2-plasmin inhibitor complex, and thrombin-antithrombin III complex were increased. The abnormality of the coagulation-fibrinolysis system and the fragility of the cerebral arteries related to Weber-Christian disease were probably the cause of the subarachnoid hemorrhage.
Basilar Artery↗
[The comparison between adult and pediatric AVMs treated by gamma knife radiosurgery].
More than 290 cases of cerebral AVM had been treated by gamma knife radiosurgery since May, 1991, among which ninety-nine cases were angiographically followed up for at least one year. Comparison of the results between adult and pediatric AVMs were made. There were seventy six adult and twenty three child cases. Intracerebral hemorrhages in their past history were found in 73.7% of adult and 91.3% of child cases respectively, and the rate of intracranial hemorrhages in the pediatric group was higher than that in the adult group. The volume of the nidus of AVM in both groups was 4.2 ml in adults and 4.8 ml in children. Grade III of the Spetzler grading system occupied about 70% of all cases and was the most common grade in both groups. Treatment was performed with a mean marginal dose of 20.0Gy in adults and 20.5Gy in children. The complete occlusion of the nidus was obtained in 45% of the adult group and 74% of the pediatric group one year after, and in 81% and 95% respectively two years after the treatment was begun. As side effects, these were two rebleedings, one radiation necrosis and one radiation-induced edema in adults. However, no side effects were observed in children. It is considered that, when using gamma knife radiosurgery, pediatric AVMs are more likely to be occluded successfully and safely than adult AVMs.
Adolescent↗