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Biomedical subjects

K Kurata

Publications and source records attributed to K Kurata.

At least 73 records · Page 4Linked to original sources

Self-organization of the velocity selectivity of a directionally selective neural network.

We first present a mathematical analysis of the relation between the parameters and the behavior of the basic module in the proposed neural network model for visual motion detection. Based on the analytical results, a learning rule is put forth that can develop velocity selectivity of directionally selective cells in the basic module. The learning rule is furthermore introduced into the total model called a 'mass model', which is constructed with many basic modules. Numerical simulation results showed that each basic module in the mass model learned in a self-organizing manner to acquire selectivity for the velocity of an input stimulus. The proposed learning rule would be plausible in the actual nervous system in that it is simple and can be described with only local information.

Animals↗

Hypofrontality does not occur with 6-hydroxydopamine lesions of the medial prefrontal cortex in rat brain.

This study examined the effect of lesions of dopamine (DA) nerve terminals the medial prefrontal cortex on local cerebral glucose utilization (LCGU) and dopamine metabolism in the rat brain. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the medial prefrontal cortex. Twenty-eight days after the lesion, concentrations of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were determined in eight brain regions with a high-performance liquid chromatographic assay. LCGU was assessed by [14C]2-deoxy-D-glucose autoradiography. The lesion produced a striking reduction in DA (to 6% of the control value), and a moderate reduction in DOPAC and HVA in the medial prefrontal cortex. The ratio of DOPAC to DA in the medial prefrontal cortex was significantly elevated in the 6-OHDA lesioned animals. In contrast to DA depletion, LCGU in the medial prefrontal cortex of the lesioned rats was unaltered when compared with the control. These findings suggest that decreased energy metabolism in the frontal cortex, i.e., hypofrontality, does not occur with decreased DA innervation of that site.

3,4-Dihydroxyphenylacetic Acid↗

T-614, a novel antirheumatic drug, inhibits both the activity and induction of cyclooxygenase-2 (COX-2) in cultured fibroblasts.

To elucidate the mechanism for the selective inhibition of prostaglandin E2 (PGE2) production in inflammatory tissue by T-614 (3-formylamino-7-methylsulfonylamino-6-phenoxy-4H-1-benzopyran-4-o ne), its effects on both the activity and the induction of cyclooxygenase (COX)-2 were investigated in vitro. T-614 inhibited the activity of purified COX-2 enzyme (IC50: 7.7 micrograms/ml), but was inactive against both COX-1 activities of microsomal and purified enzymes (IC50: > 300 micrograms/ml). On the other hand, when the inhibition of PGE2 production by T-614 was examined in the cultured fibroblasts stimulated with bradykinin, T-614 at 1 microgram/ml or less inhibited PGE2 release more effectively than that in the above cell-free system. Therefore, we examined which of the COX enzymes was expressed in bradykinin-stimulated fibroblasts by using both the reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot analyses. As a result, COX-1 mRNA was constitutively expressed in the cells, whereas COX-2 mRNA was not detected without stimulation with bradykinin, but was expressed within 30 min when stimulated. Furthermore, it was found that the addition of T-614 reduced the COX-2 mRNA levels in 30 min after stimulation. These studies suggest that at least some of inhibitory effects of T-614 on prostanoids production are mediated by the synergy of the inhibition of COX-2 activity and the inhibition of induction, and such an action of T-614 may explain the pharmacological properties of this drug.

3T3 Cells↗

Vitamin A regulates the expression of apolipoprotein AI and CIII genes in the rat.

The effect of vitamin A on the expression of apoAI and CIII genes in intact rats was studied. In vitamin A-deficient rats, the hepatic level of apoAI mRNA was increased and enhanced by an oral administration of excess retinoic acid(RA). A similar administration to normal rats caused an increase in the apoAI mRNA level in the intestine without affecting that of hepatic mRNA. Though the hepatic level of apo CIII mRNA was not affected by the vitamin A status, the intestinal level was positively regulated by vitamin A. These findings show that vitamin A regulates the expression of apolipoprotein AI and CIII genes in a tissue-specific and complex fashion.

Animals↗

Comparative study of dopamine metabolism with local cerebral glucose utilization in rat brain following the administration of haloperidol decanoate.

The effects of haloperidol decanoate on dopamine (DA) metabolism in discrete regions of rat brain were investigated and compared with changes in local cerebral glucose utilization (LCGU). The concentration of DA and its metabolite, homovanillic acid, and the alpha-methyl-p-tyrosine (alpha-MT)-induced decline of DA were measured in 6 brain regions by a high-performance liquid chromatographic assay. LCGU in 26 brain regions were examined by [14C]2-deoxy-D-glucose autoradiography. At 24-hr after intramuscular injection of haloperidol decanoate (60 mg eq/kg to haloperidol), the concentration of homovanillic acid in the prefrontal cortex, caudate-putamen, accumbens nucleus, lateral amygdala, and medial thalamus showed significant increase compared with control values. On day 21, the increase in these regions was significantly attenuated with no significant difference from the controls. Furthermore, chronic haloperidol rats showed alpha-MT-induced decline of DA to a similar extent in the control rats. LCGU on day 21 showed significant decrease in the parietal cortex, and a tendency toward decrease in the prefrontal cortex, lateral amygdala and medial thalamus compared with the controls. There was no significant change in LCGU in the caudate-putamen or accumbens nucleus. Chronic haloperidol would thus appear to affect energy metabolism mainly in the cortico-thalamo-limbic circuits, and this may not correspond well to presynaptic DA metabolism.

Animals↗

Expression cloning of a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase).

A cDNA encoding a GM3-specific alpha-2,8-sialyltransferase (GD3 synthase) was obtained from an expression cDNA library of human melanoma cell line WM266-4 by enrichment of Namalwa KJM-1 cells highly expressing GD3 using an anti-GD3 antibody and a fluorescence-activated cell sorter. Selection of B-cell line Namalwa cells expressing transfected cDNAs in the presence of anti-GD3 monoclonal antibody KM641 gave a cDNA (pAMo-GD3) encoding a protein with a type II transmembrane topology as found for mammalian glycosyltransferases. The following evidence confirms that the cDNA encodes an alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3. (i) Transfection of pAMo-GD3 into Namalwa KJM-1 cells leads to the appearance of GD3 and a GD3 synthase activity. (ii) Northern blot analysis revealed a correlation between the expression of this gene and GD3 in several cell lines. (iii) The putative COOH-terminal active domain of this cloned enzyme fused with protein A has been purified with IgG-Sepharose beads and has been shown to possess GD3-synthesizing activity, excluding the possibility that the cloned cDNA encodes a transacting factor inducing a GD3 synthase. The deduced primary sequence also contains the "sialyl motif" conserved among all the sialyltransferases cloned to date. The polymerase chain reaction analysis reveals that this gene is located on chromosome 12.

Amino Acid Sequence↗

Expression cloning of a novel alpha 1,3-fucosyltransferase that is involved in biosynthesis of the sialyl Lewis x carbohydrate determinants in leukocytes.

The sialyl Lewis x (NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)Glc-NAc) determinants serve as ligands in the selectin-mediated adhesion of leukocytes to activated endothelium or platelets. In our efforts to identify glycosyltransferases involved in the biosynthesis of those ligands, we achieved expression cloning of a novel human alpha 1,3-fucosyltransferase termed Fuc-TVII from a THP-1 cDNA library by enrichment of the Namalwa cells highly expressing that determinant with a fluorescence-activated cell sorter. Expression of the COOH-terminal catalytic domain of Fuc-TVII showed an alpha 1,3-fucosyltransferase activity for a type II oligosaccharide with a terminal alpha 2,3-linked sialic acid among various acceptors, consistent with that in vivo acceptor specificity. Alignment of the primary sequences of five alpha 1,3-fucosyltransferases and assignment of the chromosomal location of Fuc-TVII gene, together with that acceptor specificity, indicate that Fuc-TVII consists of a unique class of the alpha 1,3-fucosyltransferase family. Determination of the expression levels of these alpha 1,3-fucosyltransferases in various cells revealed that both Fuc-TVII and a myeloid fucosyltransferase Fuc-TIV were significantly expressed in myeloid lineage cells. Fuc-TVII-transfected Namalwa cells exhibited significant binding to E-selectin in contrast to little binding of the Fuc-TIV-transfected cells. These results suggest that Fuc-TVII may participate in the biosynthesis of the selectin ligands.

Antibodies, Monoclonal↗

Information processing for motor control in primate premotor cortex.

Recent neurophysiological as well as neuropsychological studies provided evidences on how various informations are processed to generate motor programs in the central nervous system. In this article, functional specializations of two distinct cortical motor areas, the dorsal and ventral aspects of the premotor cortex (PMd and PMv, respectively) of macaque monkeys, are focused to review this issue. Three major conclusions emerged from recent neurophysiological studies. First, each of movement parameters such as amplitude and direction is distinctively programmed in PMd by serial integration, rather than by parallel distributed processing. Second, in performance of conditional motor behavior, conditionally presented sensory signals are processed for motor preparation and execution of an intended act in PMd, but not in PMv. Third, PMv may be specialized for motor execution under visual guidance.

Animals↗

Site of origin of projections from the thalamus to dorsal versus ventral aspects of the premotor cortex of monkeys.

Retrograde tracers were injected into the forelimb regions of three cortical motor areas: (1) a dorsal aspect of the premotor cortex (PMd) immediately lateral to the superior precentral sulcus; (2) a ventral aspect of the premotor cortex (PMv) immediately caudal to the genu of the arcuate sulcus and lateral to the arcuate spur; and (3) the primary motor cortex (MI). Before tracer injection, single-unit recordings were made to select injection sites in the forelimb regions where neurons with set- and/or movement-related activity before forelimb movements were densely located. Following the PMd injections, labeled cells were found mainly in rostral portion of VLc and VLo. Cells projecting to PMv were found mainly in X and VPLo. Projection cells to the MI were found in VPLo, VLc, and VLo. Locations of neurons projecting to different motor areas were not overlapped in the thalamic nuclei. Combining available reports, the results suggest that major inputs to PMd come from globus pallidus and that, in contrast, cerebellum is a main source to the PMv. The differential inputs to PMd and PMv may contribute to their functional specialization.

Animals↗

5-Hydroxytryptamine release in dorsal hippocampus of freely moving rats: modulation by pindolol.

1. The aim of the present study was to investigate the origin and modulation of 5-hydroxytryptamine release in dorsal hippocampus of freely moving rats using brain microdialysis. 2. Basal release of 5-hydroxytryptamine and 5-hydroxyindole-acetic acid was 3.0 +/- 0.2 pg/15 min and 519 +/- 18 pg/15 min, respectively. Stimulation by 60 mM K+ increased 5-hydroxytryptamine release by 66%. Inclusion of 10 microM tetrodotoxin in the perfusion medium reduced 5-hydroxytryptamine release to approximately 5% of basal levels. 3. In addition, release could be modulated by the 5-hydroxytryptamine receptor agonist 8-hydroxy-2-(di-N-propylamino)-tetralin (50 % decrease) and this effect was completely blocked by the 5-hydroxytryptamine-1 receptor antagonist pindolol. 4. These data are in concordance with results from the ventral hippocampus and indicate that release of 5-hydroxytryptamine is predominantly of neuronal origin. In contrast with other studies, the authors found the non-selective 5-hydroxytryptamine-1 antagonist, pindolol, to increase 5-hydroxytryptamine release by 65% following systemic administration. This may hint at a different autoreceptor control in serotonergic fibers ascending from the median raphe as compared to the dorsal raphe nucleus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Purification and characterization of a juvenile hormone binding protein from hemolymph of the silkworm, Bombyx mori.

A juvenile hormone binding protein (JHBP) has been isolated from Bombyx mori hemolymph by gel filtration, ion-exchange chromatography, chromatofocusing and hydroxyapatite column chromatography. Gel electrophoresis indicates that the isolated protein is homogeneous in the presence or absence of a denaturing agent. The JHBP in question has a relative molecular mass of 32 kDa, determined by denaturing gel electrophoresis. Chromatofocusing analysis indicated that the JHBP is an acidic protein with pI 4.9. The protein exhibits a dissociation constant of 9.0 x 10(-8) M for JH I, 1.14 x 10(-7) M for JH II and 3.9 x 10(-7) M for JH III, and thus its affinity for JH analogues is in the order of JH I > JH II > JH III. Its amino acid composition indicates that the protein consists of 297 residues of 18 kinds of amino acids. The sequence of the N-terminus of the polypeptide chain was determined for 34 of the first 36 residues: Asp-Gln-Asp-Ala-Leu-Leu- Lys-Pro-?-Lys-Leu-Gly-Asp-Met-Gln-Ser-Leu-Ser-Ser-Ala-Thr-Gln-Gln-Phe-Le u-Glu- Lys-Thr-Ser-Lys-Gly-Ile-Pro-?-Tyr-His-.

Amino Acid Sequence↗

Differential effects of muscimol microinjection into dorsal and ventral aspects of the premotor cortex of monkeys.

1. A gamma aminobutyric acid (GABAA) receptor agonist, muscimol (Sigma, 5 micrograms/microliters solution), and a GABAB receptor agonist and antagonist, baclofen and phaclofen, respectively, were injected (1.0 microliter) into the dorsal and ventral aspects of the premotor cortex (PM) of two Japanese monkeys (Macaca fuscata), while they were performing a motor task that required wrist flexion or extension to a target. The correct movement was instructed by either 1) a conditional color cue [green or red light emitting diodes (LED)] equidistant from the targets or 2) a directional cue toward extension or flexion (right or left LED). When the green or right LED was illuminated, extension was to be performed. When the red or left LED was illuminated, flexion was required. The movement was triggered by a visual stimulus either simultaneously with the instruction stimulus or after a variable delay. 2. Before drug injection, single-unit recordings were made to select injection sites 1) in the dorsal aspect of the PM (PMd) around the superior precentral sulcus where typical set-related activity was frequently recorded and 2) in the ventral aspect of the PM (PMv) immediately caudal to the genu of the arcuate sulcus where movement-related neurons were densely located. 3. Behavioral deficits were observed primarily at the time muscimol, but not baclofen or phaclofen, was injected. Furthermore, muscimol effects were short-lasting: deficits were most frequently observed during the 10-min injection period but seldom after completion of injection. 4. When muscimol was injected into the PMd, there was an increase in the number of direction errors primarily when the conditional cues were presented. The initiated movements were similar in amplitude and velocity to the preinjection behavior. In contrast, when muscimol was injected into the PMv, many of the initiated movements showed smaller amplitudes and slower velocities, but few direction errors were made. 5. These results suggest that the PMd and PMv play differential roles in motor control: the PMd is more important than PMv in conditional motor behavior and plays a role in the preparation for forthcoming movements. In contrast, the PMv is more specialized for a role in the execution of visually guided movements.

Animals↗

[Penetration of the esophageal and gastric ulcers to the cardioaortic system following hiatus hernia: a lethal complication in the severely-handicapped].

Among the severely-handicapped, hiatus hernia (HH) and/or gastroesophageal regurgitation (GER) are not uncommon. We report here three patients with HH and/or GER. Two of them died of massive hemorrhage in the alimentary tract from the heart or the thoracic aorta due to penetration of the gastric or esophageal ulcer. The third patient died of pneumonia, but autopsy proved multiple esophageal ulcers, one of which reached the wall of the brachiocephalic artery without penetration. We propose that proper treatment for HH and/or GER is required for the severely-handicapped, including surgical intervention, before their general conditions become worse and decompensatory.

Adult↗

Changes in local cerebral glucose utilization and dopamine metabolism in the rat brain following acute administration of haloperidol.

The effects of acute administration of haloperidol on local cerebral glucose utilization (LCGU) in 26 discrete regions of the rat brain were examined by the quantitative autoradiographic [14C] 2-deoxy-D-glucose technique and compared with the changes in dopamine (DA) metabolism in 13 brain regions examined by a high performance liquid chromatographic assay. A moderate dose (0.25 mg/kg) of acute haloperidol significantly reduced LCGU in a few brain regions; a high dose (1.0 mg/kg) reduced LCGU in 11 regions including the prefrontal cortex, thalamus and other subcortical structures, but not in the caudate putamen or accumbens nucleus. However, the levels of DA metabolite in the caudate-putamen, accumbens nucleus, prefrontal cortex, and medial thalamus were strikingly elevated with both doses of haloperidol. Thus, the changes in LCGU did not parallel presynaptic DA metabolism in terms of direction or distribution, and they might represent mainly the activities of postsynaptic sites.

Animals↗

Differential effects of tight and loose 2-hour restraint stress on extracellular concentrations of dopamine in nucleus accumbens and anteromedial frontal cortex.

Changes in the extracellular dopamine (DA) concentrations were examined in the nucleus accumbens (NAS) and anteromedial frontal cortex (AMFCx) during either 2-hr loose or tight restraint stress by means of a microdialysis method. Loose restraint induced significant 100% and 30% increases in DA release in the AMFCx and NAS, respectively, and the increased DA levels returned to the control values despite continued stress. Tight restraint induced an almost constant 100-130% increase during stressing in the AMFCx and a 30% reduction in the NAS. Transient increases in DA release were observed in both regions soon after the cessation of loose, but not tight, restraint.

Animals↗

Complete remission of neuroleptic-induced Meige's syndrome by botulinum toxin treatment: a case report.

A botulinum A toxin injection has beneficial effects on patients suffering from facial and cervical spastic disorders. However, its effect almost completely disappears within three months. We have reported a case of a 23-year-old schizophrenic patient with severe neuroleptic-induced Meige's syndrome in whom botulinum toxin treatment exerted a marked effect which lasted more than 15 months after the final injection of botulinum toxin in spite of continuous neuroleptic medication. It is concluded that botulinum can be recommended as a treatment of choice in neuroleptic-induced Meige's syndrome.

Adult↗

Iatrogenic benign lymphoplasia induced by allergic contact dermatitis from squaric acid dibutylester: immunohistologic study of cellular infiltrates.

We report of a 62-year-old male patient with a dull red itchy nodule on the induction area of allergic contact dermatitis to squaric acid dibutylester, which had been used for the therapy of alopecia universalis. The excised biopsy specimen showed dense infiltration of lymphoid cells in the dermis and subcutaneous tissue, associated with the formation of lymphoid follicles. Immunohistologic analysis of the infiltrates indicated mixed proliferation of T- and B-cells. A biopsy specimen from the challenge area showed spongiosis in the epidermis and lymphoid cell infiltration in the upper dermis, while the infiltrates consisted mainly of T-cells. The following points are discussed: (i) the lesion had an iatrogenic origin and the causative agent was quite evident; (ii) the route of allergen application was only through the epidermis and not directly in the dermis; (iii) lymphoid cell infiltrates of the induction and challenge areas were different.

Allergens↗