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Biomedical subjects

M Nomoto

Publications and source records attributed to M Nomoto.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effects of talipexole on motor behavior in normal and MPTP-treated common marmosets.

Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 0.5 mg/animal i.v. once or twice) to common marmosets induced persistent parkinsonian motor deficits. The postsynaptic dopamine D2 receptor agonist properties of talipexole (B-HT 920, 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]-azepine), which is believed to be a dopamine autoreceptor agonist, were examined using normal and MPTP-treated marmosets and were compared to these properties of bromocriptine, a selective dopamine D2 receptor agonist. Talipexole (20-160 micrograms/kg i.p.) dose dependently increased motor activity and reversed the akinesia and incoordination of movement in MPTP-treated marmosets. In normal marmosets, higher doses of talipexole (80-160 micrograms/kg i.p.) produced a dose-dependent increase in motor activity, while the lowest dose (20 micrograms/kg i.p.) depressed this activity. These data for talipexole were very similar to those for bromocriptine. Talipexole had, however, several properties different from those of bromocriptine; it had a rapid onset of antiparkinsonian activity compared to bromocriptine; it had more than 25 times as much activity potency as bromocriptine; a dose of talipexole (80 micrograms/kg i.p.) sufficient to produce the activity did not induce emesis as strongly as an insufficient dose of bromocriptine (0.5 mg/kg i.p.). These results suggest that talipexole has postsynaptic dopamine D2 receptor agonist properties and that these properties of talipexole may be favorable in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Age-related effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment of common marmosets.

The effect of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on juvenile (6-8 months), young adult (2-4 years) and aged (8-10 years) common marmosets were compared. Juvenile marmosets were more resistant to the actions of MPTP and required a greater cumulative dose over a longer period to induce the same degree of motor disability observed in older animals. Young adult and aged marmosets showed an equivalent motor recovery in the 4-5 weeks following cessation of MPTP treatment, but juvenile animals were less able to compensate for the motor impairments. Losses of putamen [3H]dopamine uptake and caudate nucleus dopamine content were equivalent in young adult and aged animals. However, juvenile animals showed a more marked degree of dopamine depletion and reduction in [3H]dopamine uptake. Histological analysis showed cell loss in the substantia nigra to be most prominent in juvenile animals although it was evident in all groups. No loss of cells in the locus coeruleus was apparent in any of the groups studied, and no intraneuronal eosinophilic inclusions were seen. Greater nigral cell loss and dopamine depletion were required in juvenile animals to impair motor function. The degree of behavioural recovery was less in juvenile animals than in young adult and aged marmosets. The extent of behavioural recovery appeared linked to the severity of cell loss and was not reduced in old age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

A selective MAOB inhibitor Ro19-6327 potentiates the effects of levodopa on parkinsonism induced by MPTP in the common marmoset.

The effects of the selective and reversible MAOB inhibitor Ro19-6327 on parkinsonism in common marmosets, induced by MPTP were studied. Combined administration of Ro19-6327 with benserazide/levodopa potentiated the effects of levodopa to reverse akinesia. In a microdialysis study, the administration of Ro19-6327 was found to minimize the increase in metabolites of dopamine (DA) following injection of levodopa. These results suggest that Ro19-6327 suppresses the metabolism of DA, resulting in increased effects of levodopa on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Thus, Ro19-6327 should be useful in the treatment of patients with Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Effects of beta-adrenergic blockers on drug-induced tremors.

We studied the effect of various kinds of beta-adrenergic blockers on oxotremorine-, harmaline- and thyrotropin-releasing hormone (TRH)-induced tremors in mice. To investigate what property of beta-blockers plays the main role in suppressing tremor, we employed five beta-blockers (propranolol, atenolol, butoxamine, pindolol, and arotinolol). All drugs suppressed oxotremorine-induced tremors but none reduced harmaline-induced tremors. Even though TRH-induced tremors were decreased significantly only by propranolol and high doses of arotinolol, all drugs had a tendency to reduce the tremor. We concluded that neuropharmacological mechanisms underlying to harmaline-induced tremors were different from those of TRH- and oxotremorine-induced tremors and that features of beta-blockers (beta 1- or beta 2-selectivity, intrinsic sympathomimetic activity, and membrane stabilizing activity) did not primarily contribute to the suppression of tremors.

Adrenergic beta-Antagonists↗
PubMed1993

Synovial osteochondromatosis of the temporo-mandibular joint.

A rare case of synovial osteochondromatosis of the temporo-mandibular joint is presented. Important diagnostic information can be obtained by CT, MRI, 99m Tc bone scan and aspiration biopsy. Observation using a light microscope showed mild cellular atypia, but the hallmarks characteristic of chondrosarcoma were not found. Observation using an electron microscope showed the mature chondrocytes contained a well-developed rough endoplasmic reticulum. Histological evaluation indicated that the present case was benign synovial osteochondromatosis in an early stage.

Adult↗
PubMed1993

Misdirected reinnervation in the feline intrinsic laryngeal muscles after long-term denervation.

Nerve terminals which resembled the autonomic nerve varicosities were found at all neuromuscular junctions of the feline intrinsic laryngeal muscles after 21 months of unilateral laryngeal paralysis. The structure of muscle fibers was preserved throughout this period, although there was no evidence of regeneration of transected recurrent laryngeal nerve. In the cricothyroid muscle, misdirected reinnervation was recognized in the different pathways from the other intrinsic laryngeal muscles.

Animals↗
PubMed1993

Computed tomography in fetal methylmercury poisoning.

Cerebral computed tomography was studied in eight patients with fetal methylmercury poisoning. All patients had evidence of prenatal exposure to methylmercury and showed psychomotor retardation. All of them had abnormal computed tomography findings. The most common finding was sulcal and ventricular enlargement, with or without cisternal enlargement. These findings indicated generalized cortical and subcortical maldevelopment. The distribution of sulcal and fissural enlargement did not show specific dominance in central sulcus, calcarine fissure or cerebellum. This distribution contrasts with the location of focal atrophy present in adult methylmercury poisoning. The computed tomography findings were relatively mild compared with the clinical features and were not distinct from those in cerebral palsy.

Activities of Daily Living↗
PubMed1993

Persistent adrenergic reinnervation of previously denervated muscle in cat.

Synapse formation by aberrant nerves at chronically denervated intrinsic laryngeal muscles was observed even at 21 months after the transection of the recurrent laryngeal nerve in cats. Some of the aberrant nerves were adrenergic, and these nerve terminals were in synaptic contact with the postsynaptic membrane of the neuromuscular junctions together with non-adrenergic nerve terminals. Therefore, heterogeneous reinnervation between adrenergic nerve and muscle was found to be maintained for a long time.

Adrenergic Fibers↗
PubMed1992

Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor-channel complex in mice.

The role of the N-methyl-D-aspartate (NMDA) receptor-channel complex in ketamine-induced anesthesia was examined in mice. General anesthetic potencies were evaluated on a rating scale, which provided the data for anesthetic scores, loss of righting reflex, sleeping time and recovery time. All drugs were administered intraperitoneally. NMDA (60-300 mg/kg), an NMDA receptor agonist, dose-dependently antagonized the general anesthetic potencies of ketamine at a dose of 100 mg/kg which produced loss of righting reflex in more than 90% of the mice. On the other hand, a high dose of N-methyl-L-aspartate (400 mg/kg), a stereoisomer of NMDA, did not. A dose of 300 mg/kg of NMDA significantly shifted the dose-response curve of ketamine for loss of righting reflex to the right. A high dose of D-cycloserine (200 mg/kg), an agonist at the glycine site on the NMDA receptor complex, slightly but significantly shortened the sleeping time caused by ketamine (100 mg/kg). However, neither a critical subconvulsive dose of kainate (15 mg/kg), a kainate receptor agonist, nor a subconvulsive dose of quisqualate (120 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor agonist, reversed general anesthesia induced by 100 mg/kg of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

The rat peptidylarginine deiminase-encoding gene: structural analysis and the 5'-flanking sequence.

Genomic clones of the rat peptidylarginine deiminase (PAD)-encoding gene (PAD) were isolated, and the gene organization was analyzed by restriction mapping and nucleotide sequencing. The PAD spans more than 50 kb and contains 16 exons and 15 introns. The lengths of the introns from 0.5 kb to more than 16.5 kb. A 1.7-kb sequence in the 5'-flanking region was determined. S1 nuclease mapping revealed two putative cap sites 79 and 81 bp upstream from the N-terminal ATG codon of PAD, which had been determined by amino acid sequence analysis. This ATG was confirmed to be the translation start site, since no other ATG codon was found in the open reading frame downstream from the cap sites. The 5'-flanking sequence contains four potential SP1-binding sites, a putative Pit-1/GHF-1-binding site, four short sequences either identical or homologous to the sequences in the promoter regions of rat or human growth hormone encoding genes, as well as a sequence similar to an estrogen-responsive element. However, neither a typical TATAA box, nor CCAAT box is present. These results provide important clues for elucidating the mechanism of female-specific and/or sex cycle-dependent gene expression.

Amino Acid Sequence↗
PubMed1992

Upregulation of postsynaptic dopamine receptors in the striatum does not influence haloperidol-induced catalepsy in mice.

The incidence of haloperidol-induced catalepsy was investigated in mice whose postsynaptic dopamine (DA) receptors in the striatum had been upregulated by denervation with 6-hydroxydopamine (6-OHDA). In nonupregulated mice, which were injected with 6-OHDA 4 days before, DA in the striatum fell to 21% of the level found in vehicle-injected mice but [3H]spiperone binding to the membrane of the striatum did not increase. In upregulated mice, which were injected with 6-OHDA 28 days before, DA was at 24% and [3H]spiperone binding increased by 15%. The ED50 values (with 95% confidence limits) for haloperidol-induced catalepsy in nonupregulated mice and that in upregulated mice was 0.40 mg/kg (0.25-0.65 mg/kg) and 0.29 mg/kg (0.16-0.51 mg/kg), respectively. There was no significant difference in the incidence of catalepsy between the two groups of mice. This suggests that the intensity of catalepsy produced by the DA receptor blockade may be unaltered even when the density of receptors increases.

Animals↗
PubMed1992

Enhancement and suppression in the auditory midbrain nucleus (MLD) of the pigeon.

Auditory evoked potentials (AEPs) and spike responses were recorded from the same recording site in the nucleus mesencephalicus lateralis pars dorsalis (MLD) in pigeons with a tungsten microelectrode. Depending on the recording sites within the MLD, enhancement and suppression of the AEPs in response to clicks were observed at particular frequencies of a background continuous pure tone. Post stimulus time histograms (PSTs) of the spike responses, if available in such cases, were recorded from the same position by the same electrode. Suppression of the AEPs always occurred but enhancement occurred in only 21% of the trials. The frequencies of tone bursts that caused maximum AEP were vaguely related to the frequencies of continuous pure tones that elicited maximum suppression of the AEPs in response to clicks. However, enhancement was produced by a continuous pure tone of approximately 1.5 kHz, independent of the frequencies of tone bursts that produced maximum AEPs. Most of the PSTs in such instances showed parallel relations between the spike responses and the amplitudes of the AEPs. The nature of the enhancement and suppression of the click evoked AEPs during continuous pure tones was clearly different from those in recordings from the nucleus magnocellularis, nucleus angularis and Field L in respect to the probability of occurrence of enhancement and suppression.

Acoustic Stimulation↗
PubMed1992

Appearance of hepatocytelike cells in the interlobular bile ducts of human liver in various liver disease states.

Among 1,098 liver biopsy specimens obtained from patients with various liver diseases characterized by liver injury, 58 epithelial cells whose cytoplasms stained positively by the periodic acid-Schiff stain (digested with diastase) were recognized in the interlobular bile ducts of 37 specimens from 36 patients. Light microscopic study revealed that the cytoplasms of these cells were clear or stained weakly eosinophilic on hematoxylin and eosin staining and that the cell limits were distinct. From their reaction with periodic acid-Schiff stain and from electron microscopic observation it was clear that these cells contained an abundance of glycogen and were located among the normal bile duct cells surrounded by basement membrane. On electron microscopy, these cells had microvilli of equal sizes on their luminal surfaces and many irregularly sized microvilluslike cell membrane projections on their basal surfaces. They rested on basement membrane with basal spaces. These cells varied in size from 25.0 to 452.2 microns 2 (mean = 212.2 microns 2). In contrast, the sizes of normal bile duct cells and hepatocytes ranged from 20.0 to 69.3 microns 2 (mean = 34.2 microns 2) and from 113.0 to 860.3 microns 2 (mean = 447.0 microns 2), respectively. Immunohistochemical study with antiserum to cytokeratin 19, albumin and alpha 1-antitrypsin on serially cut frozen sections showed that some of these cells expressed markers of bile duct cells and hepatocytes. Some cells expressed only the markers of hepatocytes. Computer graphic three-dimensional reconstruction clearly demonstrated that these cells were located sparsely (but sometimes in groups) among normal interlobular bile duct cells, without any connection to the surrounding parenchymal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The usefulness of simultaneous determinations of glucosaminylation and fucosylation indices of alpha-fetoprotein in the differential diagnosis of neoplastic diseases of the liver.

The degrees of glucosaminylation (glucosaminylation index) and fucosylation (fucosylation index) of alpha-fetoprotein (AFP) were determined in serum samples of 351 patients with hepatocellular carcinoma (HCC), 47 with carcinoma metastatic to the liver from digestive organs, five with mixed cholangiocellular and HCC, and 176 with benign liver diseases. The glucosaminylation index of AFP in patients with carcinoma metastatic to the liver (42 +/- 23%, mean +/- SD) was significantly higher than that in patients with HCC (5 +/- 7%, P less than 0.001) or that in patients with benign liver diseases (2 +/- 4%, P less than 0.001). The fucosylation indices of AFP in patients with carcinoma metastatic to the liver, with HCC, and with benign liver diseases were 76 +/- 25%, 42 +/- 30%, and 4 +/- 6%, respectively. Thus, the fucosylation indices of AFP were high in two neoplastic liver diseases (carcinoma metastatic to the liver and HCC) and low in benign liver diseases, whereas the glucosaminylation indices were high in carcinoma metastatic to the liver but low in HCC and benign liver diseases. When the values of 30% and 80% were used as the level of the glucosaminylation and fucosylation indices, respectively, to discriminate carcinoma metastatic to the liver from HCC, 40 of 47 patients with carcinoma metastatic to the liver (85%) were able to be discriminated from HCC (sensitivity). The specificity, the positive predictive value, and the overall accuracy were 86% (302/351), 45% (40/40 + 47 + 3 - 2) and 86% (40 + 302/47 + 351), respectively. These data suggest that the combined information in these two indices provides a potent criterion for the diagnosis of neoplastic diseases of the liver.

Adenoma, Bile Duct↗
PubMed1991

Synapse formation by autonomic nerves in the previously denervated neuromuscular junctions of the feline intrinsic laryngeal muscles.

Nerve terminals of unknown origin at the previously denervated neuromuscular junctions (NMJ) of the feline intrinsic laryngeal muscles were investigated. Until 3 weeks after the transection of the recurrent laryngeal nerve (RLN), no axons were observed in the Büngner's bands and the NMJ, accompanied by a marked decrease of autonomic nerves around the blood vessels. At 5-6 weeks nerve varicosities labeled by 5-hydroxydopamine (5-OHDA) were observed in the Büngner's bands together with an increase of autonomic nerves around the blood vessels. At 9-30 weeks (8 cases) nerve terminals were found at the NMJ in all cases. Even if the ipsilateral vagosympathetic trunk was transected at 17 weeks, nerve terminals were found at all the NMJ 3 weeks after this treatment, indicating that nerve terminals were not from the original RLN. These nerve terminals were considered to be autonomic because nerve terminals labeled by 5-OHDA were observed. Furthermore, in the case of the removal of the superior cervical ganglion (SCG) and the nodose ganglion at 21 weeks, though nerve varicosities were found in the Büngner's bands, nerve terminals were not found 9 days after this treatment, suggesting that the ipsilateral SCG possibly played an important role. In electromyographic findings fibrillation-like activities were recognized in 8/11 cases after 5 weeks. The relationship of this phenomenon to fibrillation and muscle atrophy was discussed.

Animals↗