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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 613 records · Page 34Linked to original sources
PubMed1997

Biphasic effects of carbamazepine on the dopaminergic system in rat striatum and hippocampus.

To clarify the effects of carbamazepine (CBZ) on dopamine (DA) release and their metabolism, the extracellular and total levels of DA, its metabolites (DOPAC and HVA) and precursor, 3,4-dihydroxyphenylalanine (DOPA) in the striatum and hippocampus were studied. DA re-uptake and DOPA accumulation in the striatum and hippocampus, and monoamine oxidase (MAO) activities were also determined. After acute and chronic administrations of CBZ, the plasma concentration of CBZ associated with therapeutic activity increased the extracellular and total levels of all substances determined, whereas supratherapeutic concentration of CBZ decreased extracellular and total levels of all substances. Neither therapeutic nor supratherapeutic concentrations of CBZ affected MAO-A nor -B activities, nor DA re-uptake. DOPA accumulation caused by NSD1015 was inhibited by therapeutic and supratherapeutic concentrations of CBZ. These results suggest that a therapeutic concentration of CBZ enhances DA turnover, whereas a supratherapeutic concentration of CBZ inhibits DA turnover. These effects of CBZ on dopaminergic systems may be, at least partially, involved in the mechanisms of action of CBZ.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Effects of non-toxic and toxic concentrations of phenytoin on monoamines levels in rat brain.

To clarify the mechanisms of the antiepileptic activity of phenytoin (PHI), the effects of PHT on extracellular and total levels of monoamines (dopamine and serotonin), in rat striatum and hippocampus were studied. The plasma concentrations of PHT associated with therapeutic activity did not affect striatal and hippocampal extracellular levels of monoamines, whereas supratherapeutic concentrations of PHT decreased striatal and hippocampal extracellular levels of monoamines, in a concentration dependent manner. Toxic concentrations of PHT produced generalized seizures 'paradoxical intoxication' and an initial drastic decrease in striatal and hippocampal extracellular levels of monoamines before seizure onset, whereas the extracellular monoamines levels increased after seizures. In addition, the therapeutic concentrations of PHT did not affect monoamine turnover, whereas supratherapeutic concentrations of PHT inhibited monoamine turnover. These results suggest that monoaminergic transmission may not be involved in the antiepileptic mechanism of action of PHT, and that dysfunction of monoaminergic transmission can produce generalized tonic-clonic convulsions. Thus, the present study suggests that 'Paradoxical Intoxication' induced by toxic concentrations of PHT, at least partially, can be mediated by hypo-monoaminergic function in the brain.

Animals↗
PubMed1997

Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients.

Immunological abnormalities (IA) are frequently observed in patients with myelodysplastic syndromes (MDS). Although there have been a number of analyses of the prognostic factors, there have been few studies, if any, to determine whether IA affects prognosis. We investigated the prognosis of 153 MDS patients with or without IA who were treated at a single Japanese institute for 10 years. Nineteen of 153 patients (12%) developed autoimmune disorders. One hundred of 153 patients (63%) had an abnormality in at least one immunological laboratory test. Hypergammaglobulinemia was found in 50 of 128 (39%) patients tested, hypogammaglobulinemia was observed in 10 of 128 (8%), positivities of antinuclear antibody, RA factor. DNA antibody, and direct antiglobulin test were observed in 30%, 14%, 7% and 12%, respectively, and a CD4/CD8 ratio < 1 was observed in 20%. There was no significance in the distribution of age, MDS subtype, or sex between patients with and without IA. The survival of MDS patients without IA was significantly better than that of patients with IA, and the survival of patients with a CD4/CD8 ratio > 1 was also significantly superior to the survival of those with an inverted CD4/CD8 ratio. Patients with IA tended to die of infection or leukemic progression in comparison with those without IA, suggesting that IA may be associated with susceptibility to opportunistic infection and disease progression.

Adult↗
PubMed1997

Purification and characterization of arylalkylamine N-acetyltransferase from cockroach testicular organs.

Arylalkylamine N-acetyltransferase (NAT; EC2.3.1.87) catalyzes N-acetylation of various arylalkylamines using acetyl-CoA as a donor substrate. A type of NAT was purified 2700-fold from 451 pairs of cockroach testicular organs consisting of testis and its accessory gland. The NAT activity was recovered as a single peak on any column chromatography examined, suggesting that the testicular organ contained only one form of NAT. Five steps of successive column chromatographies gave a single protein band on SDS-polyacrylamide gel electrophoresis with estimated molecular mass of 28 kDa. The molecular mass of the native enzyme was also determined to be approximately 30 kDa by molecular sieve chromatography, indicating that the enzyme is a monomer protein. The enzyme acted on various arylalkylamines such as tryptamine, serotonin, dopamine, octopamine, norepinephrine, tyramine and methoxytryptamine, with K(m) values ranging from 20 to 50 microM. The optimum pH for these substrates was around 6.0. Internal amino acid sequences derived from two proteolytic fragments of the enzyme were determined as Leu-Leu-Gly-Glu-Asn-Gly-Asp-Glu and Phe-Phe-Phe-Leu-Glu-Glu-Pro-Leu-Asn-Ile-Ser-Leu-Gln, both of which exhibited significant homology to the C-terminal sequence of known vertebrate NATs; however, homology was less than 45%. These results suggest that a unique NAT is present in the cockroach testicular organ at high levels, and likely plays a role in the regulation of testicular function.

Amino Acid Sequence↗
PubMed1997

Early increase of gut intraepithelial mast cell precursors following Strongyloides venezuelensis infection in mice.

The time-course of differentiation/proliferation of mast cells in gut epithelium was investigated in mice infected with the nematode Strongyloides venezuelensis. After infection, expression of proliferating cell nuclear antigen increased in gut intraepithelial mast cells on days 7 to 11, followed by an increase in the number of intraepithelial mast cells from days 11 to 14. Mast cell precursors were defined as cells that formed mast cell colonies in methylcellulose culture. After infection, the numbers of mast cell precursors in the population of gut intraepithelial mononuclear cells (IEMNC) increased significantly on day 3 and returned to the pre-infection level by day 7. Mast cell precursors in Peyer's patches, mesenteric lymph nodes (MLN), and spleen also increased from day 7 p.i. Production of IL-3 and IL-4 in MLN and spleen were increased between 7 and 11 days p.i. These results show that murine intestinal mastocytosis is initiated by an early increase in mast cell precursor number in the gut epithelium followed by proliferation/differentiation of mast cells. Mast cell precursor numbers increased even before the production of IL-3 and IL-4 in MLN and spleen, suggesting that some local factors might be involved in this phenomenon.

Animals↗
PubMed1997

Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient.

A female patient with ALL received a bone marrow transplant (BMT) from an unrelated donor with a one locus HLA mismatch. The donor was heterozygous at the HLA-A locus, while the patient was homozygous at this locus. The patient had cytomegalovirus (CMV) antigenemia on day 42 following an intensive preparative regimen that included anti-thymocyte globulin and BU+CY+TBI to prevent graft rejection. Ganciclovir was given initially for the treatment of CMV antigenemia, although the patient soon developed severe myelosuppression. The patient's hematopoietic recovery was poor, and CMV and human herpesvirus-6 (HHV-6) were detectable in the peripheral blood. Severe CMV retinitis was treated with foscarnet and the intraocular injection of ganciclovir. The CMV retinitis improved and the marrow gradually recovered. CMV and HHV-6 were no longer detectable in the peripheral blood. Foscarnet and intraocular injection of ganciclovir appeared to be an effective treatment for CMV retinitis in this myelosuppressed BMT patient.

Adult↗
PubMed1997

The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation.

The metabotropic glutamate receptor mGluR5, but not the closely related mGluR1, is expressed in cultured astrocytes, and this expression is up-regulated by specific growth factors. We investigated the capability and underlying mechanisms of mGluR5 to induce oscillatory responses of intracellular calcium concentration ([Ca2+]i) in cultured rat astrocytes. Single-cell [Ca2+]i recordings indicated that an mGluR-selective agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), elicits [Ca2+]i oscillations in good agreement with the growth factor-induced up-regulation of mGluR5 in cultured astrocytes. A protein kinase C (PKC) inhibitor, bisindolylmaleimide I, converted a 1S,3R-ACPD-mediated oscillatory response into a nonoscillatory response. In addition, the PKC activator phorbol 12-myristate 13-acetate completely abolished the [Ca2+]i increase. These and other pharmacological properties of 1S,3R-ACPD-induced [Ca2+]i oscillations correlate well with those of the cloned mGluR5 characterized in heterologous expression systems. Furthermore, the potential involvement of protein phosphatases in [Ca2+]i oscillations is suggested. The present study demonstrates that mGluR5 is capable of inducing [Ca2+]i oscillations in cultured astrocytes and that phosphorylation/dephosphorylation of mGluR5 is critical in [Ca2+]i oscillations, analogous to the cloned mGluR5 expressed in heterologous cell lines.

Animals↗
PubMed1997

Effects of adenosine receptor subtypes on hippocampal extracellular serotonin level and serotonin reuptake activity.

To clarify the effects of adenosine receptor subtypes (A1, A2, and A3) on hippocampal serotoninergic function, hippocampal extracellular serotonin (5-HT) levels were determined by in vivo microdialysis in freely moving rats under various conditions. Both adenosine and an adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine, decreased extracellular 5-HT levels, whereas an adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT), and caffeine increased these levels. A selective A2A receptor agonist (CGS-21680), an adenosine A2 receptor agonist (PD-125944), an adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), and an adenosine A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA), did not affect extracellular 5-HT levels. When the adenosine A1 receptor was blocked by CPT, the hippocampal extracellular 5-HT level was increased by adenosine, CGS-21680, and PD-125944, and decreased by caffeine, DMPX, and APNEA. When both adenosine A1 and A2 receptors were blocked by CPT and DMPX, the extracellular 5-HT level was decreased by adenosine, caffeine, and APNEA. The hippocampal extracellular 5-HT level was not affected by administration of APNEA alone, but was decreased by this agent when the adenosine A1 receptor was blocked, irrespective of whether the adenosine A2 receptor was functional. These inhibitory effects of adenosine, caffeine, and APNEA on extracellular 5-HT levels, during both adenosine A1 and A2 receptor blockade, were inhibited by selective 5-HT reuptake inhibitors. These results indicate that the stimulatory effects of the adenosine A2 receptor and the inhibitory effects of the A3 receptor on hippocampal extracellular 5-HT levels are masked by the inhibitory effects of the adenosine A1 receptor.

Animals↗
PubMed1997

Omentopexy for anastomotic dehiscence after tracheal sleeve pneumonectomy.

A 54-year-old male patient developed anastomotic dehiscence following tracheal sleeve pneumonectomy for squamous-cell carcinoma of the right lung. Among various possible methods of treatment, omentopexy was adopted and proved very effective in the treatment of such a fatal complication.

Anastomosis, Surgical↗
PubMed1997

The effect of nitric oxide synthase inhibitor on form-deprivation myopia.

PURPOSE: Form-deprivation myopia (FDM) is believed to result principally from actions of substances that modulate information processing in the retina. We used a chick model to investigate what role nitric oxide (NO), a gaseous neuromodulator, might play in the development of FDM. METHODS: We injected different concentrations of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (30 ml) into the left eyes and the same volume of saline into the right eyes of 6-day-old chicks. Both eyes of most chicks were occluded for 6 days with translucent goggles. After removal of the goggles, the refraction was measured by retinoscopy and the axial lengths with an A-mode ultrasound. In some chicks we measured the concentration of NOx (nitrite and nitrate) in the retina. A few chicks, not wearing occluders after injection of L-NAME and saline, ERG and refraction, were examined 6 days after the treatment. RESULTS: In chicks that wore occluders, refractive error and axial length were significantly less affected in eyes injected with L-NAME (180, 360, or 540 mM) compared to control (right) eyes. ERG changes were reversible, except in eyes injected with the highest concentration (540 mM) of L-NAME. The eyes of chicks, injected with L-NAME and reared without occlusion, had normal refractive values. After 6 days of form deprivation, the concentration of NOx in the retina of eyes injected with L-NAME (180 mM) was significantly less than the concentration in eyes injected with saline. CONCLUSIONS: The injection of L-NAME before occlusion of developing chick eyes leads to reversible modifications in retinal function and inhibits the development of form-deprivation myopia.

Animals↗
PubMed1997

Isolation and chromosomal localization of a cornea-specific human keratin 12 gene and detection of four mutations in Meesmann corneal epithelial dystrophy.

Keratin 12 (K12) is an intermediate-filament protein expressed specifically in corneal epithelium. Recently, we isolated K12 cDNA from a human corneal epithelial cDNA library and determined its full sequence. Herein, we present the exon-intron boundary structure and chromosomal localization of human K12. In addition, we report four K12 mutations in Meesmann corneal epithelial dystrophy (MCD), an autosomal dominant disorder characterized by intraepithelial microcysts and corneal epithelial fragility in which mutations in keratin 3 (K3) and K12 have recently been implicated. In the human K12 gene, we identified seven introns, defining eight individual exons that cover the coding sequence. Together the exons and introns span approximately 6 kb of genomic DNA. Using FISH, we found that the K12 gene mapped to 17q12, where a type I keratin cluster exists. In this study, four new K12 mutations (Arg135Gly, Arg135Ile, Tyr429Asp, and Leu140Arg) were identified in three unrelated MCD pedigrees and in one individual with MCD. All mutations were either in the highly conserved alpha-helix-initiation motif of rod domain 1A or in the alpha-helix-termination motif of rod domain 2B. These sites are essential for keratin filament assembly, suggesting that the mutations described above may be causative for MCD. Of particular interest, one of these mutations (Tyr429Asp), detected in both affected individuals in one of our pedigrees, is the first mutation to be identified within the alpha-helix-termination motif in type I keratin.

Base Sequence↗
PubMed1997

Genetic remodeling of gangliosides resulted in the enhanced reactions to the foreign substances in skin.

Several lines of transgenic mice with gangliosides GM2/GD2 synthase gene were established, and the expression levels of the transgene in brain, liver, spleen and thymus were analyzed by comparing with those in their litter mates. Among four tissues, brain and skin showed markedly high expression levels of the transgene in Northern blotting. Particularly, transgenic mice skin showed about 10-fold higher expression of GM2/GD2 synthase gene than the wild type mice skin. Therefore, alterations in the morphology, glycolipid components, and responses to the exogenous stimulations in the transgenic mice skin were examined. Gangliosides in the transgenic skin were dramatically converted from GM3 to GM1, whereas no morphological changes were observed. However, when skin flap test was performed with insertion of nylon membranes under the skin flaps, much stronger inflammatory reactions consisting of edema, marked thickness, and cell infiltration were observed in the transgenic mice compared with the wild type. Similar enhanced inflammatory reaction was also observed in the skin injected by silicon gel, and in the peritoneal reaction to the injected casein. Main cell population in these inflammatory reactions consisted of neutrophils, suggesting an increased sensitivity of neutrophils to chemotactic factors in the transgenic mice.

Animals↗
PubMed1997

An NADP-glutamate dehydrogenase from the green alga Bryopsis maxima. Purification and properties.

NADP-glutamate dehydrogenase (EC 1.4.1.4:NADP-GDH) was purified to electrophoretic homogeneity from the multinuclear-unicellular green marine alga in Siphomales, Bryopsis maxima, and its properties were examined. M(r) of the undenatured enzyme was 280 kDa, and the enzyme is thought to be a hexamer of 46 kDa subunit protein. Optimum pHs for the reductive amination and oxidative deamination were 7.5 and 8.2-9.0 respectively. The enzyme displayed NADPH/NADH-specific activities with a ratio of 18:1. Apparent K(m) values for 2-oxoglutarate, ammonia, NADPH, glutamate and NADP+ were 3.0, 2.2, 0.03, 3.2 and 0.01 mM respectively. The enzymochemical characteristics of the GDH were studied and compared to those of other species. The B. maxima GDH was insensitive to 5 mM Ca(2+) and to 1 mM EDTA in contrast to higher plant NAD-GDHs. Chemical modifications with DTNB and pCMBS suggested that cysteine residues are essential for the enzymatic activity as in other species GDHs. The GDH was not affected by 1 mM purine nucleotides, suggesting that the enzyme is not allosteric, in contrast to animal NAD(P)-GDHs and fungal NAD-GDHs.

Amino Acid Sequence↗
PubMed1997

Neuropathic arthropathy caused by paraneoplastic sensory neuropathy. A case report.

Neuropathic arthropathy of both knees after paraneoplastic sensory neuropathy developed in a 64-year-old woman. The patient was found to have small cell lung cancer 2 months after the onset of a sensory neuropathy that was diagnosed as paraneoplastic sensory neuropathy, a nonmetastatic neurologic complication in patients with malignancy. The onset of paraneoplastic sensory neuropathy was followed by the gradual onset of neuropathic arthropathy. This is the first well documented report on neuropathic arthropathy in a patient with paraneoplastic sensory neuropathy.

Carcinoma, Small Cell↗
PubMed1997

Infection of an HIV-1/SIVmac chimeric virus having HIV-1 env to macaque monkeys via the vaginal cavity.

We previously reported that an HIV-1/SIVmac chimeric virus (designated as NM-3rN) having HIV-1 env efficiently infected macaque monkeys by intravenous inoculation. In this study, this chimeric virus was atraumatically inoculated into the vaginal cavity of two rhesus and one cynomolgus monkeys. Although antibody response and detection of proviral genome by PCR were observed in both rhesus monkeys, virus recovery was only once from PBMC in one of them. In the cynomolgus monkey, no virus was recovered and proviral DNA detection was rare. Thus, vaginal inoculation with NM-3rN resulted in poor systemic infection, implying the presence of selective pressure while passing through mucosal membranes.

Animals↗