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M Nomoto

Publications and source records attributed to M Nomoto.

205 records · Page 12Linked to original sources
PubMedDate not supplied

Involvement of N-methyl-D-aspartate (NMDA) receptors in noncompetitive NMDA receptor antagonist-induced hyperlocomotion in mice.

The role of the N-methyl-D-aspartate (NMDA) receptors in hyperlocomotion induced by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801), a potent and selective noncompetitive NMDA receptor antagonist, was examined in male ddY mice. A low dose of MK-801 [0.2 mg/kg, intraperitoneally (IP)] produced a marked increase in locomotor activity without obvious staggering gait. In contrast, a high dose (1 mg/kg, IP) induced a typical motor syndrome characterized by increased locomotor activity, stereotyped behavior, and severe ataxia. NMDA (60-120 mg/kg, IP), an NMDA receptor agonist, dose dependently antagonized hyperlocomotion induced by a low dose of MK-801 (0.2 mg/kg). However, even a high convulsive dose of NMDA (240 mg/kg, IP) could not completely antagonize the hyperactivity induced by MK-801. On the other hand, neither a high dose of N-methyl-L-aspartate (400 mg/kg, IP), a stereoisomer of NMDA, nor a critical subconvulsive dose of kainate (10 mg/kg, IP), a non-NMDA receptor agonist, reversed MK-801-induced hyperlocomotion. The activity induced by MK-801 was potently suppressed by low doses of haloperidol (0.05-0.1 mg/kg, IP), a dopamine (DA) receptor antagonist, in a dose-dependent manner. These data for MK-801 were similar to those for phencyclidine and ketamine, other noncompetitive NMDA receptor antagonists. These results suggest that noncompetitive NMDA receptor antagonist-induced hyperlocomotion is mediated, at least in part, by NMDA receptor antagonism, although this hyperactivity may also involve dopaminergic mechanisms through indirect (perhaps by reducing NMDA receptor-mediated neurotransmission) and/or direct (by inhibiting DA uptake) effects on DA neurons.

Animals↗
PubMedDate not supplied

Ultrastructural and histochemical study of the motor end plates of the intrinsic laryngeal muscles in amyotrophic lateral sclerosis.

Motor end plates of the intrinsic laryngeal muscles in amyotrophic lateral sclerosis (ALS) were examined light and electron microscopically. Light microscopically, typical neurogenic changes such as small angulated fibers and grouped atrophy were found in the intrinsic laryngeal muscles. Acetylcholinesterase (AchE) activities of the neuromuscular junctions (NMJ) of many fibers in ALS were decreased as compared with those of the controls. Some end-plate areas on each fiber detected by AchE histochemistry were larger than those of the controls. Ultrastructurally, muscle fibers in ALS specimens showed several changes; increased number of lipofuscin granules and/or nuclei, numerous mitochondria, and disappearance of the myofilaments. The NMJ also showed various degrees of structural changes. Some NMJ appeared almost normal. Others showed the absence of nerve terminals and Schwann cells covering the former junctional sites. Their primary synaptic clefts were flattened, and the secondary synaptic clefts were relatively well preserved. On occasion, several small nerve terminals were seen on the severely distorted postsynaptic folds, suggesting regenerative findings. In severely degenerated muscle fibers, the NMJ could not be found.

Acetylcholinesterase↗
PubMedDate not supplied

Gamma-ray induced hepatocarcinogenesis in p53-deficient mice.

BACKGROUND: Mutations in the p53 gene are frequent genetic alterations in human hepatocellular carcinoma (HCC), but, little is known of the molecular genetic changes that occur during murine hepatocarcinogenesis. MATERIALS AND METHODS: To characterize the properties of constitutive p53 deficiency that contribute to liver tumor development, a total of 168 F1 mice of two different strains (C3H, which are susceptible to hepatocarcinogenesis and MSM [Mus. M. molossinus] with a single null p53 allele) were exposed to a single 3-Gy dose of whole-body gamma-irradiation at 4 weeks of age and observed for a period of 360 days. The genotype of the mice and the p53 spectrum of the tumors were investigated by polymerase chain reaction (PCR) analysis. RESULTS: Thirty-five gamma-ray-induced HCCs were obtained as a result of this experiment. 11 (40%) of the mice with liver tumor were wild-type for p53. All liver tumors examined retained the wild-type p53 allele, indicating that p53 itself may not be a target for radiation-induced alteration. Only two p53-deficient mice in the liver tumor group developed thymic lymphomas. The p53-deficient mice showed no significant differences in the number, size, or growth rate of HCC or in the apparent development of HCC. CONCLUSION: These results indicate that p53 deficiency does not enhance the rate of development or degree of malignancy of radiation-induced HCC in mice but may instead favor the development of multiple primary cancers.

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