Search PubMed⌕ Search

Biomedical subjects

N Mizuno

Publications and source records attributed to N Mizuno.

At least 235 records · Page 13Linked to original sources

Molecular cloning and characterization of the rat NMDA receptor.

A complementary DNA encoding the rat NMDA receptor has been cloned and characterized. The single protein encoded by the cDNA forms a receptor-channel complex that has electrophysiological and pharmacological properties characteristic of the NMDA receptor. This protein has a significant sequence similarity to the AMPA/kainate receptors and contains four putative transmembrane segments following a large extracellular domain. The NMDA receptor messenger RNA is expressed in neuronal cells throughout the brain regions, particularly in the hippocampus, cerebral cortex and cerebellum.

Amino Acid Sequence↗

Cholinergic projections from the globus pallidus to the lateral amygdaloid nucleus in the cat.

Direct projections from the globus pallidus (GP) to the lateral amygdaloid nucleus (A1) were found in the cat by the anterograde and retrograde tracing methods. Pallido-amygdaloid fibers originated mainly from the caudal half of the GP and distributed throughout the entire extent of the A1; most densely in the lateral part of the A1. Choline acetyltransferase immunohistochemistry in combination with retrograde fluorescent tracing indicated that most pallido-amygdaloid neurons were cholinergic.

Amygdala↗

Non-dopaminergic projections from the substantia nigra pars lateralis to the inferior colliculus in the rat.

The substantia nigra pars lateralis (SNI) of the rat was found, by the anterograde and retrograde tracing methods, to send projection fibers to the peripheral shell region surrounding the central nucleus of the inferior colliculus (IC), bilaterally with a clear-cut ipsilateral dominance. SNI neurons sending their axons to the IC were distributed throughout the entire rostrocaudal extent of the SNI. None of these SNI neurons showed tyrosine hydroxylase-like immunoreactivity.

Animals↗

Electron microscopic identification of axons containing melanin-concentrating hormone in the lamprey, Lampetra fluviatilis L.

Melanin-concentrating hormone-like immunoreactivity (MCH-LI) was examined in the hypothalamo-hypophysial region of the lamprey. At the light microscopic level, MCH-LI neuronal cell bodies were shown with the peroxidase anti-peroxidase method; they were seen in the hypothalamic region close to the third ventricle. MCH-LI axons were observed to run toward the proximal neurosecretory contact region (PNCR) and the most proximal part of the neurohypophysis. Electron microscopic analysis with the immunogold method revealed that presumed secretory granules within axonal profiles showed MCH-LI. MCH-LI axonal profiles were most often seen on or near the basement membrane of connective tissue layer separating the PNCR from the hypophysial pars distalis.

Animals↗

Retinofugal projections in the house musk shrew, Suncus murinus.

Retinofugal projections in the house musk shrew (Suncus murinus) were studied with the WGA-HRP method. After WGA-HRP injection into the vitreous cavity of one eye, terminal labeling was seen in the suprachiasmatic nucleus, dorsal and ventral lateral geniculate nuclei, pretectum and superficial layer of the superior colliculus. The terminal labeling in the suprachiasmatic nucleus was more marked on the side ipsilateral to the injection than on the contralateral side, whereas that in other regions was seen mainly on the contralateral side. A retino-intergeniculate leaflet projection was observed. No unequivocal terminal labeling was found in the lateroposterior thalamic nucleus.

Animals↗

Pallidocortical projections to the tempolar polar gyrus in the cat.

Marked projections from the globus pallidus (GP) to the temporal polar gyrus (TPG) of the cat were found by means of the PHA-L (Phaseolus vulgaris leucoagglutinin) and WGA-HRP (horseradish peroxidase conjugated to wheat germ agglutinin) methods. Pallidocortical fibers to the TPG originate mainly from the middle levels of the GP, and terminate all layers of the TPG cortex, especially in layers I, II and III. The GP neurons projecting to the TPG are large-multipolar or small-bipolar neurons. Almost all of these GP neurons show choline acetyltransferase-like immunoreactivity.

Afferent Pathways↗

Topographical projections from the cerebral cortex to the nucleus of the solitary tract in the cat.

The distribution of cerebral cortical neurons sending projection fibers to the nucleus of the solitary tract (NST), and the topographical distribution of axon terminals of cortico-NST fibers within the NST were examined in the cat by two sets of experiments with horseradish peroxidase (HRP) and HRP conjugated with wheat germ agglutinin (WGA-HRP). First, HRP was injected into the NST. In the cerebral cortex of these cats, neuronal cell bodies were labeled retrogradely in the deep pyramidal cell layer (layer V): After HRP injection centered on the rostral or middle part of the NST, HRP-labeled neuronal cell bodies were distributed mainly in the orbital gyrus and caudal part of the infralimbic cortex, and additionally in the rostral part of the anterior sylvian gyrus. After HRP injection centered on the caudal part of the NST, labeled neuronal cell bodies were seen mainly in the caudoventral part of the infralimbic cortex, and additionally in the orbital gyrus, posterior sigmoid gyrus and rostral part of the anterior sylvian gyrus. The labeling in the infralimbic cortex, orbital gyrus and anterior sylvian gyrus was bilateral with a predominantly ipsilateral distribution, while that in the posterior sigmoid gyrus was bilateral with a clear-cut contralateral dominance. In the second set of experiments, WGA-HRP was injected into the cerebral cortical regions where neuronal cell bodies had been retrogradely labeled with HRP injected into the NST: After WGA-HRP injection into the orbital gyrus, presumed axon terminals in the NST were labeled in the rostral two thirds of the nucleus bilaterally with an ipsilateral predominance. After WGA-HRP injection into the rostral part of the anterior sylvian gyrus, a moderate number of presumed axon terminals were labeled throughout the whole rostrocaudal extent of the NST bilaterally with a slight ipsilateral dominance. After WGA-HRP injection into the middle and caudal parts of the anterior sylvian gyrus, no labeling was found in the NST. After WGA-HRP injection into the caudal part of the infralimbic cortex, presumed terminal labeling in the NST was seen throughout the whole rostrocaudal extent of the nucleus bilaterally with a dominant ipsilateral distribution. After WGA-HRP injection into the posterior sigmoid gyrus, however, no terminal labeling was found in the NST. The results indicate that cortico-NST fibers from the orbital gyrus terminate in the rostral two thirds of the NST, while those from the infralimbic cortex and the rostral part of the anterior sylvian gyrus project to the whole rostrocaudal extent of the NST.

Animals↗

Distribution of axons showing calcitonin gene-related peptide- and/or substance P-like immunoreactivity in the sensory trigeminal nuclei of the cat.

Distribution of axons with calcitonin gene-related peptide (CGRP)-like and/or substance P (SP)-like immunoreactivity (LI) within the sensory trigeminal nuclei was examined in the cat before and after trigeminal rhizotomy. Axons with CGRP-LI or SP-LI were seen throughout the principal sensory trigeminal nucleus (Vp) and spinal trigeminal nuclei, including the medullary dorsal horn (MDH). They were densely distributed particularly in the dorsolateral part of the dorsal subnucleus of the Vp, ventromedial marginal zone of the ventral subnucleus of the Vp, dorsomedial and ventromedial parts of the oral spinal trigeminal nucleus, ventromedial and lateral marginal zones of the interpolar spinal trigeminal nucleus, and lamina I, outer part of lamina II and lamina V of the MDH. Most of the CGRP-LI axons exhibited SP-LI, while many SP-LI axons did not show CGRP-LI. After trigeminal rhizotomy, almost all CGRP-LI axons disappeared from the ipsilateral sensory trigeminal nuclei, while a considerable number of SP-LI axons remained intact throughout the nuclei; these SP-LI axons did not show CGRP-LI. The results indicate that CGRP-LI axons within the sensory trigeminal nuclei exhibit SP-LI and are of peripheral origin, and that SP-LI axons without CGRP-LI are of central origin.

Animals↗

Somato-, branchio- and viscero-motor neurons contain glutaminase-like immunoreactivity.

Immunocytochemistry combined with a fluorescent dye tracer method revealed that somatic, branchial and visceral motoneurons in the brainstem and spinal cord of the rat contain phosphate-activated glutaminase (PAG). An excitatory neurotransmitter glutamate is synthesized mainly through this enzyme. Among these motoneurons, neurons in the dorsal motor nucleus of the vagus nerve (dmnX), autonomic preganglionic neurons in the spinal cord and urethral sphincter motoneurons (DL) were most intensely immunostained. PAG is co-expressed with choline acetyltransferase, calcitonin gene-related peptide or galanin in these neurons. These findings, together with the findings that motor endplates in urethral sphincter muscle contain PAG and PAG-like immunostaining in dmnX motoneurons was decreased after axotomy, suggest that glutamate is a co-transmitter of acetylcholine in motoneurons. Brainstem motoneurons were moderately stained, while somatic motoneurons in the spinal cord other than DL, showed very weak staining for PAG. However, they showed intense PAG-like immunoreactivity at their premature stage, suggesting that glutamate has some effects on the maturation of these neurons. A variety of functional roles of glutamate in motoneurons is discussed.

Animals↗

Effect of tretinoin on collagen gel contraction induced by mouse 3T3 fibroblasts.

Balb/3T3 fibroblasts were cultured in type I collagen gel and the effects of tretinoin (all-trans-retinoic acid) were examined on cell growth and the gel contraction produced by cells. Cell proliferation was suppressed and the degree of gel contraction was enhanced by the addition of 10(-7) and 10(-6) M tretinoin. Growth and gel contractility of transformed cells derived from the Balb/3T3 cells were not influenced by this agent. Addition of 12-O-tetradecanoylphorbol ester, which is known to antagonize tretinoin in several biological processes, enhanced gel contraction synergistically with tretinoin. These results suggest that tretinoin influences cell-to-collagen interactions.

Animals↗

Effects of butylated hydroxyanisole on ornithine decarboxylase activity and its gene expression induced by phorbol ester tumor promoter.

Butylated hydroxyanisole (BHA) is a phenolic antioxidant that has been found to suppress the activity of skin tumor promoters. In this study, we investigated the effect of BHA on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion) and its gene expression induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in mouse skin. TPA-induced ODC activity was markedly inhibited by the topical application of 55 mumol of BHA (the inhibition rate at 6 h was about 80%). In Northern and dot-blot analysis, the TPA-induced increase in ODC mRNA was shown to be markedly reduced by the same dose of BHA (the inhibition rate at 4 h was about 60%). These results suggest the involvement of a decrease in ODC gene expression in the mechanism of the inhibition of ODC activity by BHA.

Animals↗

Differential effects of cyclosporine A on ornithine decarboxylase activity induced by ultraviolet-B and PUVA in mouse skin.

The inhibitory effect of cyclosporine A (CsA) on the activity of ornithine decarboxylase (ODC) induced by phorbol ester tumor promoter has been reported. In the present study, the effects of CsA on ODC activity induced by ultraviolet-B (UV-B) and PUVA in the skin of the SKH/hr 1 hairless mouse were investigated. Topical application of CsA (1.7 mumol) to the dorsal skin irradiated with 50 mJ/cm2 UV-B did not remarkably change ODC activity. On the other hand, if CsA was applied simultaneously with 3 J/cm2 UV-A 1 h after treatment with 0.3% 8-methoxypsoralen, PUVA-induced ODC activity was suppressed by about 60% at 12 and 24 h after UV-A irradiation. In the dot blotting analysis of ODC-specific mRNA level, a significant but slight decrease in ODC mRNA level (about 20% inhibition) was observed in the PUVA-treated group compared with the control group (vehicle and UV-A). The inhibition of PUVA-induced ODC activity by CsA may have been caused in part by the decrease in ODC mRNA level and in part by a post-transcriptional regulation mechanism.

Animals↗

Allergic contact and photocontact dermatitis due to psoralens in patients with psoriasis treated with topical PUVA.

The incidence and clinical features of allergic contact and/or photocontact dermatitis due to psoralens were examined in 371 patients with psoriasis treated with topical PUVA. The psoralen derivatives used in the study were 8-methoxypsoralen (8MOP), 3-carbethoxypsoralen (3CPs), 4,6,4'-trimethylangelicin (TMA) and 7-methyl pyridopsoralen (MPP). Of 371 patients treated with 8MOP, three (0.8%) developed an acute dermatitis in the PUVA-treated areas. This incidence was significantly lower (P less than 0.01) than that for 3CPs (four of 10 patients) or that for TMA (six of 17 patients). None of the seven patients receiving MPP on PUVA had a reaction. It was confirmed that these dermatitis reactions were due to contact and/or photocontact allergy to psoralens by several methods that include patch and photopatch tests, photopatch test mapping, determination of the minimal erythema dose (MED) and immunohistochemistry.

Adult↗

Structural elucidation of the 8-methoxypsoralen oxidized product that inhibits the chemotactic activity of polymorphonuclear neutrophils toward anaphylatoxin C5a.

The chemical structure of the 8-methoxypsoralen oxidized product that inhibits the chemotactic activity of anaphylatoxin C5a was determined to be 2,3-dihydro-2,9-dimethoxy-3-hydroxy-7-oxo-7H-furo[3,2-g] [1]benzopyran. Its minimal concentration required to obtain the maximum inhibition of C5a des Arg (1 x 10(-8) M) chemotactic activity is 2.5 x 10(-8) M. Bioactivity of this substance was maintained for 2 weeks, stored in a dark room at room temperature under aerobic conditions. There is a possibility that this substance may be useful in the treatment of immune complex diseases.

Chemotaxis, Leukocyte↗

Effect of age on the gastrointestinal absorption of acyclovir in rats.

Drug elimination from the body after intravenous administration of acyclovir (20 mg kg-1) was delayed in 1-week-old rats but the pharmacokinetic data for 2.5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0-infinity h (AUC) after oral administration of acyclovir (20 mg kg-1) decreased with increasing age. The absolute bioavailabilities for 1-, 2.5-, 3- and 8-week-old rats were 77.59, 51.52, 14.61 and 7.30%, respectively. The gastrointestinal absorption of poorly absorbed acyclovir was good for rats younger than 2.5 weeks but dropped abruptly between 2.5 and 3 weeks of age. The intestinal membrane permeability of acyclovir was studied using the everted sac method. The rate of transfer of an initial concentration of 10 microM acyclovir from the mucosal to the serosal side was constant until 60 min in rats of different ages while the rate in 2.5-week-old rats was significantly greater than that in 3-, 4- and 8-week-old rats. Abrupt in-vivo and in-vitro changes were observed in the experimental results between 2.5- and 3-week-old rats; this period coincided with the weaning period of the rat. The membrane transport mechanism of acyclovir in 2.5- and 8-week-old rats was also studied. Cumulative transferred amounts of acyclovir were linear (r = 0.99) over the range 5 microM-1 mM and dose-independent. The influence of metabolic inhibitors (sodium azide, 2,4-dinitrophenol, ouabain), purine and pyrimidine analogues (2-deoxyguanosine, guanine, adenine, uridine) and temperature on the permeation of acyclovir was studied. The permeation of acyclovir was inhibited only by 2-deoxyguanosine and guanine in 2.5-week-old rats. These results suggest that throughout the maturation period, the gastrointestinal absorption mechanism of acyclovir is predominantly via passive diffusion with little or no active or facilitated transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Acyclovir↗

Effects of ryo-kan-kyomi-sin-ge-nin-to extract on degranulation of and histamine release from rat mast cells.

The effects of Ryo-kan-kyomi-sin-ge-nin-to (RKSG)) extract, a medicinal agent traditionally used in China and Japan for treatment of asthma, on the degranulation of and histamine release from rat mast cells were studied. At a concentration of 5 mg/ml RKSG, degranulation of mast cells stimulated either by antigen (DNP-Ascaris) or compound 48/80 was markedly suppressed. At a concentration of 1-5 mg/ml RKSG, histamine release from mast cells due to application of either antigen or compound 48/80 was inhibited in a dose-dependent fashion. These results suggest that RKSG may be useful for the treatment of type I allergy-related diseases.

Animals↗

In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle.

The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗