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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 1,063 records · Page 59Linked to original sources

Induction of peripheral-type benzodiazepine receptors in mouse brain following thioacetamide-induced acute liver failure.

To investigate the possible role of peripheral-type benzodiazepine receptors (PBR) in hepatic encephalopathy, we examined expression of PBR in mouse brain following thioacetamide (TAA)-induced acute liver failure. Treatment of mice with TAA resulted in an increase in the number of binding sites of the PBR ligand [3H] Ro5-4864 to brain homogenates, with no significant change in affinity of the ligand. The order of potency of different ligands to compete against [3H] Ro5-4864 binding in the brain of TAA-treated mice was Ro5-4864 > PK11195 > diazepam > protoporphyrin IX, findings similar to those in the control. Northern blot analysis revealed an increase in PBR/isoquinoline binding protein (PBR/IBP) mRNA in mouse brain following TAA treatment, in a time- and dose-dependent manner. These results indicate that the increased number of PBR in the brains of TAA-treated mice relates to the induction of PBR/IBP expression and suggest that the induction of PBR in brain may contribute to pathogenesis of hepatic encephalopathy.

Animals↗

An acetophenone glycoside from Exacum affine.

A new acetophenone glycoside, affinoside, was isolated from the aerial parts of Exacum affine and its structure was determined as 2-O-primeverosylpaenol. The known glucosides, gentiopicroside, 2'-O-E/Z-p-coumaroylloganin and glucopaeonol, were also identified.

Acetophenones↗

Histological and biochemical evaluation of osteogenic response in porous hydroxyapatite coated alumina ceramics.

We compared the osteogenic response in porous alumni (Al) and hydroxyapatite coated porous alumni ceramic (HA/Al) by grafting rat bone marrow cells with these implants subcutaneously in the back of syngeneic rats. The ceramics did not show any bone formation without marrow, but did when combined with marrow cells. The osteogenesis in HA/Al began directly on the ceramic surface, but in Al began away from the ceramic surface, and fibrous tissue interposition was seen between the de novo bone and its surface. Alkaline phosphatase activity and bone specific bone gla protein content in HA/Al with marrow were both about three times higher than in Al with marrow. These results indicate that HA/Al has excellent osteoconductive properties and that a composite of marrow and HA/Al is clinically applicable osteogenic biomaterial.

Alkaline Phosphatase↗

Expression of Na+/myo-inositol cotransporter mRNA in the inner ear of the rat.

We have demonstrated the cellular localization of Na+/myo-inositol cotransporter (SMIT) mRNA in the rat inner ear by in situ hybridization. In the cochlea, the most intense SMIT mRNA signals were observed in fibrocytes of the spiral ligament, moderate signals were found in the spiral limbus, inner hair cells and spiral ganglion cells, while the hybridization signals were almost undetectable in the marginal cells of the stria vascularis and outer hair cells. In the vestibular system, moderate hybridization signals were found in the sensory epithelium, fibrocytes and vestibular ganglion cells. These findings suggest that SMIT plays an important role in maintenance of intracellular ionic balance and cell volume in the inner ear, especially in the fibrocytes associated with generation of the ion gradients between the endolymph and perilymph.

Animals↗

Expression of Na+/myo-inositol cotransporter mRNA in normal and hypertonic stress rat eyes.

We studied the localization of Na+/myo-inositol cotransporter (SMIT) mRNA in normal and hypertonic stress rat eyes by in situ hybridization histochemistry using cRNA probes. SMIT mRNA signals were observed in the iris-ciliary body, the lens epithelial cells, and the ganglion cell layer and the inner nuclear layer of the retina. There was a rapid increase on SMIT mRNA in the retina of hypertonic stress rats compared with control rats. These findings suggest that Na+/myo-inositol cotransporter gene expression is osmotically regulated in vivo to protect retinal neuronal function against hypertonic stress.

Animals↗

Widespread brain distribution of mRNA encoding the orphan neurotransmitter transporter v7-3.

Orphan transporter v7-3 is a member of a new subfamily of Na+, Cl- dependent neurotransmitter transporters with two large extracellular loops. Distribution of v7-3 mRNA was investigated in the rat brain. In situ hybridization study revealed that v7-3 mRNA was widely distributed in the rat central nervous system, including the olfactory bulb, the hypothalamus, the cerebral cortex, the hippocampus, and the cerebellum. In addition, intense v7-3 mRNA expression was found in the motor nuclei including the oculomotor nucleus, abducens nucleus, trigeminal motor nucleus, facial nucleus, hypoglossal nucleus and ventral horn of spinal cord. Intense hybridization signals were also observed in the nuclei containing monoaminergic neurons, such as locus coeruleus, the substantia nigra pars compacta, the ventral tegmental area, the dorsal raphe nucleus and the median raphe nucleus. This multifocal and broad nature of the v7-3 distribution suggests widespread roles for this gene product in neurons mediating several important brain function.

Animals↗

Rapid and transient up-regulation of Na+/myo-inositol cotransporter transcription in the brain of acute hypernatremic rats.

The osmoregulatory system is well developed in the brain. Osmolytes contribute to maintenance of cell volume and cellular functions without changing intracellular ionic composition. Myo-inositol is regarded as one of the major osmolytes in the brain. In the present study, we investigated the changes in expressions of sodium myo-inositol cotransporter (SMIT) mRNA in the brain of acute hypernatremic rats by in-situ hybridization and Northern blot methods. Under moderate acute hypernatremic conditions, SMIT mRNA level increased markedly at 1 h and returned to almost control levels at 3 h, in accordance with plasma Na+ concentrations. Especially, distinct increases in SMIT mRNA expression were observed in the granule cells and glial cells in the cerebellum. These findings indicate that SMIT plays an important role in osmoregulation, especially in the early stages of acute hypernatremia in the brain.

Animals↗

PAF and PAF acetylhydrolase in the nervous system.

PAF acetylhydrolase is a key enzyme of PAF inactivation. Intracellular PAF acetylhydrolase isoform Ib is a heterotrimeric enzyme composed of alpha-, beta- and gamma-subunits. The beta- and gamma-subunits act as a catalytic unit and their amino acid sequences are homologous. The alpha-subunit is not essential for catalytic activity but is a product of the causative gene for Miller-Dicker lissencephaly, suggesting this subunit plays an important role in brain development.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Function of type II phospholipase A2 in dopamine secretion by rat neuronal PC12 cells.

When rat pheochromocytoma PC12 cells, which had differentiated into neuron-like cells following culture with nerve growth factor, were activated with glutamate, approximately 40% of their type II phospholipase A2 (PLA2) was released into the extracellular medium. Glutamate-stimulated secretion of dopamine from PC12 cells was suppressed by type II PLA2 inhibitors. Exogenous type II PLA2 added alone directly elicited release of dopamine from PC12 cells. Thus released type II PLA2 may be involved in the regulation of neurotransmitter exocytosis by PC12 cells.

Animals↗

Endosonographic characterization of duodenal elevated lesions.

BACKGROUND: Endoscopic diagnosis of duodenal elevated lesions is problematic for two reasons. Endoscopic biopsy often fails to confirm a histologic diagnosis of submucosal lesions. Moreover, a biopsy specimen is often insufficient to verify a differential diagnosis of mucosal lesions. In this study, we evaluated the usefulness of endosonography in the resolution of these problems. METHODS: The endoscopic and endosonographic features of 15 duodenal elevated lesions that had been confirmed histologically in our hospital were reviewed retrospectively. RESULTS: Of the 15 cases, 8 were submucosal lesions (lipoma, Brunner's gland hyperplasia, lymphangioma, carcinoid tumors, leiomyoma, and malignant lymphoma); the rest were mucosal lesions. A correct histologic diagnosis based on endoscopic biopsies was obtained in only 6 cases (three submucosal lesions and three mucosal lesions). On the other hand, ultrasonography was useful in the characterization of all submucosal lesions based on their echo level, layer of origin, and tissue homogeneity. As for mucosal lesions, the depth of infiltration was correctly estimated with endosonography. Either endoscopic resection or surgery was selected on the basis of endosonographic information. CONCLUSIONS: We conclude that endosonography is useful in the differential diagnosis of submucosal lesions and in determining suitable treatment methods for duodenal mucosal and submucosal lesions.

Biopsy↗

Endoscopic resection of gastrointestinal submucosal lesions: a comparison between strip biopsy and aspiration lumpectomy.

BACKGROUND: Endoscopic diagnosis and treatment of gastrointestinal submucosal lesions is still not established. We evaluated the clinical usefulness of two resection methods for submucosal lesions, using a "nonrandomized surgeon" design. METHODS: The strip biopsy method was evaluated at Tenri Hospital and the aspiration lumpectomy method was used at Kyoto University Hospital. The inclusion criteria for selecting patients were endosonographic findings indicating a tumor location within the submucosa. RESULTS: Seventy-seven patients were treated. The size of the specimens (mean +/- SEM) was 20.7 +/- 0.9 mm for the aspiration lumpectomy group and 14.0 +/- 0.8 mm for the strip biopsy group (p < 0.01). Aspiration lumpectomy was adequate for a definitive histologic diagnosis in 95% of the cases (36 of 38) as compared with 77% (30 to 39) of the cases treated by strip biopsy (p = 0.047). The eradication rate was 87% for the aspiration lumpectomy group, and 74% for the strip biopsy group (p = 0.274). The complication rate resulting from these procedures (hemorrhage, mean 5%) was acceptable. Repeated endoscopic examinations revealed no recurrence except for one lymphangioma. CONCLUSIONS: Endoscopic resection, especially aspiration lumpectomy, provides a significant benefit for accurate final diagnosis and eradication of submucosal lesions.

Adolescent↗

Germline mutations of the RET proto-oncogene in pedigree with MEN type 2A: DNA analysis and its implications for pediatric surgery.

To assess the feasibility of screening for multiple endocrine neoplasia type 2A (MEN 2A), the authors used DNA sequence analysis to evaluate the RET proto-oncogene in a kindred with MEN 2A. The kindred consisted of 95 members (1 to 79 years of age) and their spouses, and spanned five generations. Genomic DNA was extracted from peripheral blood lymphocytes or lymphoblastoid cell lines established from the family members, and the RET gene was amplified by polymerase chain reaction (PCR) using RET-specific primers (10q 11.2) and was sequenced. Periodic endocrine screening also was performed, by measuring the plasma calcitonin concentration after provocation with pentagastrin (0.5 microgram/kg intravenously) to assess its reliability for detecting the associated neoplasms. Nineteen patients were confirmed to have MEN 2A by medical records or the screening program. The DNA sequence of the PCR products from clinically established MEN 2A patients showed a mutation at codon 634 (TGC-->CGC) that resulted in an amino acid change from cysteine to arginine. Endocrine screening tests showed that six other family members had a mutated RET protooncogene. DNA sequencing can detect high-risk cases at a preclinical stage of the disease. The establishment of mutated MEN 2A gene carriers allows pediatric surgeons to consider total thyroidectomy at a very early stage of neoplasm development (C-cell hyperplasia) or even prophylactically.

Adolescent↗

Reference intervals for serum granulocyte colony-stimulating factor levels in children.

OBJECTIVE: To determine age-adjusted reference intervals for children for serum granulocyte colony-stimulating factor (G-CSF) levels. DESIGN: We determined the serum G-CSF levels of 168 disease-free children who were term neonates to 15 years of age with a highly sensitive chemiluminescent enzyme immunoassay. RESULTS: The lowest values (5 ng/L) exceeded the detectable limit (1 ng/L) of this assay technique. The G-CSF levels were highest on the day of birth (mean +/- SD 147 +/- 146 ng/L); thereafter values decreased to 46 +/- 33 ng/L in the early neonatal period and to 23 +/- 10 ng/L in the late neonatal period. The G-CSF levels both on the day of birth and in the early neonatal period were significantly higher than in all older age groups. No significant differences were found among any of the age groups after 4 weeks of age. The G-CSF values were correlated with both blood leukocyte counts (r = 0.496, p < 0.0001) and neutrophil counts (r = 0.547, p < 0.0001). In children older than 4 weeks of age (n = 128), the 95% reference interval for G-CSF values was 5 to 42 ng/L. CONCLUSIONS: Our study in disease-free children revealed that change in serum G-CSF levels are age dependent and are correlated with neutrophil counts. Determination of reference intervals for the neonatal period requires further study.

Adolescent↗

Implication of ATP receptors in brain functions.

The possible implication of P2-purinoceptors in brain functions is reviewed. Involvement of P2-purinoceptors in memory and learning (Section 2) is suggested by ATP release from hippocampal slices [Wieraszko, A., Goldsmith, G. and Seyfried, T. N. (1989) Brain Res. 485, 244-250], induction of fast synaptic currents in cultured hippocampal neurons [Inoue, K., Nakazawa, K., Fujimori, W. and Takanaka, A. (1992a) Neurosci. Lett. 134, 294-299] and long-lasting enhancement of the population spikes [Wieraszko, A. and Seyfried, T. N. (1989) Brain Res. 491, 356-359; Nishimura, S., Mohri, M., Okada, Y. and Mori, M. (1990) Brain Res. 525, 165-169; Fujii, S., Kato, H., Furuse, H., Ito, K., Osada, H., Hamaguchi, T. and Kuroda, Y. (1995) Neurosci, Lett. 187, 130-132], as well as ATP release on glutamate stimulation to evoke an increase in intracellular Ca2+ in hippocampal cells [Inoue, K., Koizum, S. and Nakazawa, K. (1995) NeuroReport 6, 437-440]. Moreover, mRNAs for certain types of P2x-purinoceptors are present in the hippocampus [Collo, G., North, R. A., Kawashima, E., Merlo-Pich, E., Neidhart, S., Surprenant, A. and Buell, G. (1996) J. Neurosci. 16, 2495-2507]. It is likely, therefore, that ATP may be involved in modulation of synaptic efficiency in the hippocampus. The implication of ATP in schizophrenia is suggested by the fact that antipsychotic drugs inhibit ATP-evoked responses in PC12 cells [Koizumi, S., Ikeda, M., Nakazawa, K., Inoue, K., Ito, K. and Inoue, K. (1995b) Biochem. Biophys. Res. Commun. 210, 624-630] without blocking the action of dopamine D2 receptors. Involvement of P2-purinoceptors in Sections 4 ("Pain and cognition") and 5 ("Central regulation of the autonomic system") are also discussed.

Animals↗

Interleukin 1 beta markedly stimulates nitric oxide formation in the absence of other cytokines or lipopolysaccharide in primary cultured rat hepatocytes but not in Kupffer cells.

To investigate whether a single inflammatory cytokine could stimulate nitric oxide formation in the absence of other cytokines or lipopolysaccharide (LPS), NO was measured by the redox chemiluminescence method in primary cultured rat hepatocytes and in rat Kupffer cells. Interleukin (IL) 1 beta, but neither IL-6, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), nor LPS stimulated NO formation in a dose-dependent manner and induced half-maximal effects at 30 pmol/L. Maximal stimulation was achieved at 12 to 16 hours after the addition of 1I nmol/L of IL-1 beta, and was 50- to 60-fold above basal levels in rat hepatocytes. The combined effect of these cytokines with LPS or IFN-gamma on NO formation was also examined. Neither LPS nor IFN-gamma affected the IL-1 beta-induced NO formation. TNF-alpha, however, stimulated IL-1 beta-induced NO formation, while IL-6 inhibited it, although independently these cytokines had no effect on NO formation. None of the cytokines tested stimulated NO formation in cultured rat Kupffer cells. In hepatocytes, the NO formation induced by IL-l beta was blocked by both the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) and by IL-1 receptor antagonist (IL-1ra). Furthermore, IL-1 beta markedly increased NOS activity, and this increase in activity was accompanied by the expression of inducible NOS (iNOS) messenger RNA (mRNA). This study clearly demonstrated that IL-1 beta markedly stimulates NO formation in hepatocytes, in the absence of other cytokines or LPS.

Animals↗