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Biomedical subjects

M Nomoto

Publications and source records attributed to M Nomoto.

At least 145 records · Page 8Linked to original sources
PubMed1991

Ketamine-induced hyperlocomotion associated with alteration of presynaptic components of dopamine neurons in the nucleus accumbens of mice.

The underlying mechanisms of ketamine-induced hyperlocomotion were examined in mice. An intraperitoneal (IP) injection of ketamine (3-150 mg/kg) increased locomotor activity in a dose-dependent fashion. A low dose of ketamine (30 mg/kg) produced peak locomotion within the first 10 min followed by a rapid decline. In contrast, a high dose (150 mg/kg) inhibited locomotor activity to the control level during the first 30 min. Thereafter the activity gradually increased and reached a peak at approximately 2 h followed by a gradual decline. The hyperactivities induced by both low and high doses of ketamine were inhibited by a low dose of haloperidol (0.10 mg/kg, IP), a dopamine (DA) receptor antagonist. However, neither a high dose of phenoxybenzamine (10 mg/kg, IP), an alpha-blocker nor a high dose of propranolol (20 mg/kg, IP), a beta-blocker inhibited the hyperactivities. Destruction of catecholaminergic terminals by 6-hydroxydopamine suppressed ketamine-induced hyperlocomotion. Regional brain monoamine assays revealed that, at peak locomotion, a low dose of ketamine (30 mg/kg) selectively increased DA turnover in the nucleus accumbens which is a forebrain region believed to be involved in the initiation and regulation of locomotor activity, while a high dose (150 mg/kg) increased not only DA but also norepinephrine and serotonin turnover in many regions of the brain. In vitro, ketamine slightly provoked [3H]DA release from nucleus accumbens and striatal slices to a similar extent, but inhibited synaptosomal uptake of [3H]DA in the nucleus accumbens to a greater degree than in the striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1991

Ultrastructural and histochemical study of the neuromuscular junctions in the denervated intrinsic laryngeal muscle of the cat.

Morphological changes and acetylcholinesterase (AchE) activity in the neuromuscular junctions (NMJ) of the normal and denervated posterior cricoarytenoid muscle (PCA muscle) of the cat were studied. Two days after denervation, the nerve terminals at the NMJ had almost disappeared. Six weeks after denervation, intensity of AchE activity at the former junctional site (FJS) was unchanged histochemically. At this stage, primary synaptic clefts were distorted and the Schwann's cells covered the FJS. Fourteen weeks after denervation, AchE activity at the FJS had decreased in contrast to that of the non-affected side. Calcitonin gene-related peptide (CGRP) was also investigated at the NMJ of the normal PCA muscles immunocytochemically. The present study shows that CGRP coexists with Ach in the nerve terminals of the PCA muscles and may be involved in the regulation of the contractile function of the intrinsic laryngeal muscle.

Acetylcholinesterase↗
PubMed1991

[Juvenile parkinsonism in monozygotic twins].

A pair of monozygotic twins concordant for juvenile Parkinsonism are described. These twin sisters have lived together until 18 years old. Twin A noted tremor in the right hand and right-sided stiffness and slowness at the age 20. Initially, a marked improvement was shown with L-dopa treatment. However, one year after the beginning of treatment, dopa-induced dyskinesia appeared. Twin B noted tremor and right-sided stiffness and basal ganglia calcification in both patients. These twin patients suggest that genetic factors may play an important role in the cause of juvenile Parkinsonism.

Adult↗
PubMed1990

1-Methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) is less neurotoxic than MPTP in the common marmoset.

Four adult marmosets were treated with increasing doses of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-methyl-MPTP) in the range 0.23-4.3 mg/kg i.p. to give a cumulative dose of 11.0-11.6 mg/kg over a 6-10 day period. After 4 days of treatment, and as the dosage was gradually increased, the animals exhibited mild motor deficits. These abnormalities slowly declined over the following 1-6 week period. In contrast, similar treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (1-4 mg/kg i.p.) for 3-5 days in a cumulative dose of 6.9-9.2 mg/kg produced gross impairment of motor function which persisted throughout the 5 weeks period of observation. Administration of 2'-methyl-MPTP for 6-10 days caused some decrease in dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC), but not homovanillic acid (HVA) content in the caudate nucleus in animals 5-6 weeks after the start of treatment. There was a small decrease in [3H]dopamine uptake into putamen synaptosomes. This contrasted with the marked decreases in all these parameters observed after MPTP treatment of common marmosets. Histological examination of the substantia nigra from the four animals treated with 2'-methyl-MPTP did not show degeneration or loss of dopamine-containing cell bodies in the zona compacta. In contrast, MPTP caused severe destruction of these pigmented nigral neurones. In the common marmoset 2'-methyl-MPTP does not appear to show the same neurotoxic action as MPTP itself. This contrasts with findings in the mouse where 2'-methyl-MPTP is more toxic to dopamine-containing cells of substantia nigra than MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Postural myoclonus associated with long-term administration of neuroleptics in schizophrenic patients.

Postural myoclonus associated with long-term administration of neuroleptics was demonstrated in schizophrenic patients. Sixty patients who had been taking neuroleptics for more than 3 months were investigated for myoclonus and the relationships between postural myoclonus and age, duration of illness, duration of medication, current daily dose, cumulative dose, occurrence of abnormal finger movement, parkinsonism, and tardive dyskinesia were evaluated. Twenty-three patients (38%) showed postural myoclonus when holding the hands forward with the elbow joints flexed at about 90%. Male patients showed a higher incidence of myoclonus than female patients. Patients with myoclonus had been given significantly higher doses of neuroleptics than those without myoclonus. There was a significant correlation between the occurrence of myoclonus and abnormal finger movement. Electromyographic recordings in 7 patients with prominent myoclonus revealed that arrhythmic jerks occurred in the extensor carpi radialis and posterior deltoid muscles and that the jerks on the left and right side were not synchronized. Clonazepam reduced the frequency of the myoclonic activity.

Adult↗
PubMed1990

Structure and in vitro transcription of the rat CYP2A1 and CYP2A2 genes and regional localization of the CYP2A gene subfamily on mouse chromosome 7.

The CYP2A1 and CYP2A2 genes code for hepatic steroid hydroxylases and differ in their development regulation and expression in male and female rats. In order to explore the mechanism of regulation of these two genes, both genes were isolated and sequenced, their upstream regions compared, and their promoters transcribed in a cell-free system derived from liver. The CYP2A1 gene was completely sequenced and spanned 12,835 bp. The CYP2A2 gene was sequenced except for 1.5 and 12 kbp in the second and fifth introns, respectively. This gene was about 10 kbp longer than CYP2A1. Both genes possess nine exons that displayed overall 93% nucleotide similarity. DNA 4544 and 5529 bp upstream from the CYP2A1 and CYP2A2 genes, respectively, was also sequenced, and the transcription start sites were determined. Both genes had typical TATA boxes but did not contain CCAAT boxes within -100 bp of their polymerase start sites. CYP2A1, however, contained a reverse CCAAT box between -85 and -90. Search of the Gene Bank revealed a 255 bp region that lies -3 kbp upstream from the transcription start site of CYP2A1 displaying similarity with retrovirus polymerase. Two regions upstream of CYP2A2 were also found that displayed 90% sequence similarity with the consensus long interspersed middle repetitive element (LINE). In addition, an unusual 1.6 kbp inserted sequence was detected between -165 and -1779 bp upstream of the CYP2A2 gene that appears to be a retropseudogene. A nuclear extract derived from adult hepatocytes was used to direct in vitro transcription of the CYP2A1 and CYP2A2 gene promoters. Both genes were accurately transcribed in extracts derived from livers of male and female rats. This result is surprising in view of the fact that the CYP2A1 gene is expressed in adult female rats while the CYP2A2 gene is expressed exclusively in adult males. The CYP2A1 promoter was more actively expressed in both extracts than that of CYP2A2. By analyzing the segregation pattern of CYP2A genes in backcross offspring from an interspecies cross between the laboratory strain NFS/N and the wild mouse Mus musculus musculus, the Cyp2a subfamily was mapped proximal to the Gpi-1 locus near the centromere on chromosome 7.

Amino Acid Sequence↗
PubMed1990

Pathoepidemiological features of adult T-cell lymphoma/leukemia in an endemic area: Kagoshima, Japan.

In order to elucidate the pathological and epidemiological features of malignant lymphoma (ML), particularly of adult T-cell lymphoma/leukemia (ATLL) in the Kagoshima district, age-adjusted and age-specific incidence rates of malignant lymphomas were estimated on 3239 histologically confirmed cases between the years 1963 and 1987. There was a marked increase in the incidence rate from 1976 (4.9) to 1982 (8.5) due to the increase of T-cell lymphomas. The increase was not conspicuous after 1982. Immunohistochemically, all of the 429 MLs found in 1985 and 1986 were examined on paraffin sections and 70 ATLL cases on fresh frozen sections. T-cell ML comprised 65.3%, B-cell ML 30.5%, Hodgkin disease 2.6%, and histiocytic ML 1.2%. Most of ATLL cells were phenotypically CD4+ CD8-, 14% of ATLL cases showed CD4+ CD8+, 6% were CD4- CD8+, and 7% were CD4- CD8-. The simulataneous expression of IL 2 and IL 2R was seen in 8 (16%) out of 56 patients examined. Therefore, a proliferation by autocrine mechanism does not seem to be a major course of ATLL progression.

Age Factors↗
PubMed1990

[Two cases of HTLV-I associated myelopathy (HAM) complicated with Sjögren's syndrome, T-lymphocyte alveolitis and arthropathy].

Two cases of HTLV-I-associated myelopathy (HAM) complicated with Sjögren's syndrome (SjS), T-lymphocyte alveolitis and arthropathy were reported. Case 1 was a 55-year-old woman. Since 40 years of age she had been suffering from repetitive pulmonary infection. She also noted polyarthralgia since 42 years of her age and was diagnosed as SjS at her age 43. She developed gait disturbance since April 1988. Case 2 was a 65-year-old woman. She began to have gait disturbance at 62 years of age. A right knee joint pain started in December 1988. The two cases have the following features in common: 1. The diagnosis of HAM is definite because of pyramidal signs and positive anti-HTLV-I antibody in both serum and cerebrospinal fluid. 2. The histological findings of the minor salivary glands are compatible with SjS. 3. Differential cell count in bronchoalveolar lavage fluid (BALF) showed an increase in lymphocytes which suggested the presence of clinical or subclinical T-lymphocyte alveolitis. 4. A mono-or polyarthropathy is observed. These findings are suggestive that HAM is not the disease restricted within the central nervous system but the disease with systemic involvement which may be caused by the activated T-lymphocytes. Thus the two cases are interesting for the understanding of the pathogenesis of HAM.

Aged↗
PubMed1989

Transient depletion of nucleus accumbens dopamine content may contribute to initial akinesia induced by MPTP in common marmosets.

Acute treatment of common marmosets with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused an initial profound akinesia and other motor deficits. However, over the following months akinesia gradually disappeared although the animals remained clumsy and poorly coordinated. At 10 days following MPTP treatment there was a profound decrease in the dopamine, HVA and DOPAC content of the caudate nucleus, putamen and nucleus accumbens. By 3-4 months following MPTP treatment the animals had largely recovered from their akinesia, but the caudate nucleus and putamen dopamine, HVA and DOPAC content remained low. In contrast, the dopamine content of the nucleus accumbens had returned towards normal and the metabolite levels were higher than at 10 days. No overall alterations in 5HT or 5HIAA levels were observed at either time point. The transient and reversible nature of dopamine loss in the nucleus accumbens may contribute to the initial profound akinesia exhibited by common marmosets treated with MPTP. The restoration of dopamine levels in the nucleus accumbens may be partially responsible for the subsequent recovery of motor function that occurs in MPTP-treated marmosets.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Stereoselective reversal of MPTP-induced parkinsonism in the marmoset after dermal application of N-0437.

The selective dopamine D-2 receptor agonist N-0437 produced a rapid and dose-dependent reversal of motor deficits lasting 90-120 min following i.p. or oral administration of the racemate to MPTP-treated common marmosets. In contrast, topical application of (+/-)-, (+)- or (-)-N-0437 to the skin of MPTP-treated animals did not alter locomotor activity in the initial 4 h although other motor disabilities were reduced. However, 24 h following application of the racemate or the (-) enantiomer both locomotor activity and the other motor deficits induced by MPTP were improved. The increase in locomotor activity returned to basal values by 48-52 h following application of the racemate to the skin and by 72-76 h following administration of (-)-N-0437; the other motor deficits induced by MPTP were reduced for up to 72-76 h by both (+/-)- and (-)-N-0437. Application to skin of the (+) enantiomer produced no behavioural improvement or stimulation of locomotor activity. Transdermal administration of the active enantiomer of N-0437 may be of value in producing a prolonged reversal of parkinsonian motor deficits in man.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Increased caudate dopamine turnover may contribute to the recovery of motor function in marmosets treated with the dopaminergic neurotoxin MPTP.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets initially impaired motor function, but a partial recovery occurred over the following weeks. At both 10 days and 4-6 weeks following MPTP treatment, [3H]dopamine ([3H]DA) uptake into synaptosomal preparations of putamen was markedly decreased. At 10 days and 4-6 weeks following MPTP treatment DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the caudate nucleus and nucleus accumbens were substantially reduced. However, the levels of HVA and DOPAC in caudate nucleus were higher at 4-6 weeks than at 10 days. The ratio of (DOPAC + HVA)/DA in caudate nucleus was elevated at 10 days following MPTP treatment and even more so at 4-6 weeks. No change in Bmax or Kd values for [3H]spiperone binding to caudate preparations were observed. The recovery of motor function in marmosets observed following MPTP treatment may result partially from a compensatory increase in caudate DA turnover by remaining neurones.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Treatment with a selective MAO B inhibitor prevents loss of dopamine in the nucleus accumbens of MPTP-treated common marmosets.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets induced motor deficits, associated with a marked decrease in the uptake of [3H]dopamine into synaptosomes in the putamen and a reduction in the content of dopamine in both caudate nucleus and nucleus accumbens. Histological analysis showed a marked loss of dopamine-containing cells in the zona compacta of the substantia nigra and less loss in the ventral tegmental area. Treatment of animals with the selective monoamine oxidase (MAO) B inhibitor, MDL 72145 (0.5 or 2.0 mg/kg) prior to, during and following administration of MPTP partially protected animals from the motor abnormalities induced by administration of MPTP alone. Both doses inhibited the onset of akinesia but only the large dose of MDL 72145 prevented the occurrence of other motor abnormalities. Moreover, while MDL 72145 (2.0 mg/kg) prevented the loss in uptake of [3H]dopamine into synaptosomes of the putamen, this was only partly prevented using the smaller dose. Similarly, while MDL 72145 (2.0 mg/kg) prevented loss of dopamine in the caudate, only partial protection was afforded by the smaller dose. However, in the nucleus accumbens, both doses of MDL 72145 prevented the depletion of dopamine, occurring in this region. Histological examination of the substantia nigra showed little or no cell loss in animals receiving the larger dose of MDL 72145 but a moderate cell loss in animals receiving the smaller dose. No damage was observed in the ventral tegmental area of animals treated with MDL 72145 (2.0 mg/kg) and only mild cell loss in those receiving the smaller dose.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

Primary squamous cell carcinoma of the parotid gland: a case report with electron microscopic findings.

Primary squamous cell carcinoma of the parotid gland is a rare tumor. Histological and ultrastructural features of a primary squamous cell carcinoma arising in the right parotid gland is presented. Light microscopically the tumor consisted of poorly differentiated squamous cell nests. PAS reaction was negative. Ultrastructurally the tumor cells were oval or spindle shaped and the cytoplasmic processes were frequently found. The majority of the tumor cells contained numerous intermediate filaments in their cytoplasm. No secretory granule was found. The desmosomes were well developed. It is known that mucoepidermoid carcinoma may be often misdiagnosed as squamous cell carcinoma. These findings can enable us to distinguish primary squamous cell carcinoma from mucoepidermoid carcinoma of the parotid gland.

Carcinoma, Squamous Cell↗
PubMed1989

[Histochemical study of acetylcholine receptors at the neuromuscular junctions of the cat posterior cricoarytenoid muscle using erabutoxin B].

Acetylcholine receptors (AchRs) at the neuromuscular junctions of the cat posterior cricoarytenoid muscle (PCA muscle) were demonstrated by using erabutoxin b (Eb) which has a curare-like action. Eb is one of the short-chain neurotoxins which is obtained from Laticauda-semifasciata. At the light microscopic level, the localization of the neuromuscular junctions was detected on the muscle fiber by rhodamine-labeled Eb (TMR-Eb) under a fluorescein microscopy. For the electron microscopy horseradish peroxidase-labeled Eb (HRP-Eb) was used. After incubation with HRP-Eb conjugate the tissue was fixed in a mixture of paraformaldehyde and glutaraldehyde, then embedded in Epon. The reaction products were largely restricted to the postsynaptic membrane at the neuromuscular junction. Acetylcholinesterase (AchE) activity was also demonstrated electron microscopically by Karnovsky's and Lewis' methods respectively. The reaction products were localized at the subneural apparatus of the neuromuscular junction. Both these results were compared.

Animals↗
PubMed1989

[An ultrastructural study of the neuromuscular junctions of the cat intrinsic laryngeal muscles. I. Denervation and reinnervation].

Morphological changes of the neuromuscular junctions induced by denervation and reinnervation have been investigated electronmicroscopically using cat intrinsic laryngeal muscles. Two experiments were performed: 1. simple transection of the unilateral recurrent laryngeal nerve at the level of the second tracheal ring; 2. neurorrhaphy immediately after the transection at the same level. 1. All the ipsilateral intrinsic laryngeal muscles except for the cricothyroid muscle were denervated 48 hours after the transection of the recurrent laryngeal nerve. In the denervated neuromuscular junctions some primary synaptic clefts were narrowed and others were flattened, while the secondary synaptic clefts were structurally preserved. 2. Some of the regenerating axons returned to the neuromuscular junctions 3 weeks after neurorrhaphy, and all the muscle fibres were reinnervated after 6 weeks. The structural features of the reinnervated neuromuscular junctions were as follows; 1) synaptic vesicles of the nerve terminals were more densely observed, 2) the original postsynaptic membranes were only partially in contact with the regenerated nerve terminals. These conditions persisted until 22 weeks after neurorrhaphy, when the appearance of remyelination was found in the vicinity of the neuromuscular junctions. Using an evoked electromyogram, the presence of neuromuscular transmission was observed 3 weeks after neurorrhaphy, indicating that the structural maturation of the neuromuscular junction was not necessary for neuromuscular transmission.

Animals↗
PubMed1989

[An ultrastructural study of the neuromuscular junctions of the cat intrinsic laryngeal muscles. II. Synapse formation by autonomic nerves].

The purpose of this study is to identify the origin of the nerve terminals of unknown origin observed at the previously denervated neuromuscular junctions in the cat intrinsic laryngeal muscles. The results were as follows: 1. Until 3 weeks after the transection of the recurrent laryngeal nerve, no nerve terminals were found at the neuromuscular junctions of the intrinsic laryngeal muscles except for the cricothyroid muscle, and no nerve fibres were detected in the Schwann tubes formed by Schwann cells and perineural cells. In addition, autonomic nerves around the vessels in the muscles were markedly decreased. 2. At 6 weeks, accompanied by an increase of autonomic nerves around the vessels, nerve fibres and nerve varicosities containing a number of large granular vesicles were observed in the Schwann tubes. 3. From 9 to 30 weeks, nerve terminals containing large granular vesicles were found at the neuromuscular junctions in all cases, even though the superior laryngeal nerve or the vagal nerve was transected on the ipsilateral side. 4. A spontaneous discharge was recognized in 6/8 cases after 6 weeks, but an evoked electromyogram could not be recognized. 5. The synaptic vesicles of the nerve terminals were labelled by 5-hydroxydopamine (5-OHDA), which was used as a marker for the sympathetic nerve. From these results, it was indicated that if the transected recurrent laryngeal nerve was prevented from regenerating, the autonomic nerves around the vessels entered into the Schwann tubes and reached the denervated neuromuscular junctions, instead of the motor nerve. The effect of autonomic nerves on muscle fibres was discussed.

Animals↗