Search PubMed⌕ Search

Biomedical subjects

M Otsuka

Publications and source records attributed to M Otsuka.

At least 127 records · Page 7Linked to original sources
PubMed1998

Fibroblast growth factor (FGF)-9 immunoreactivity in senile plaques.

We examined fibroblast growth factor (FGF)-9 immunoreactivity in human hippocampal sections of Alzheimer's disease (AD). FGF-9 immunoreactivity was observed in dystrophic neurites of senile plaques in AD and control cases, in addition to the hippocampal and cortical neurons. The amyloid core and neurofibrillary tangles lacked immunoreactivity. FGF-9 immunoreactive astrocytes were conspicuous in AD brains. FGF-9 may be involved in the neuropathology of AD.

Alzheimer Disease↗
PubMed1998

Effect of geometrical cement size on in vitro and in vivo indomethacin release from self-setting apatite cement.

The relationship between in vitro and in vivo indomethacin (IMC) release from a self-setting bioactive apatite cement and cement size were investigated. Differently sized apatite cements (total weight, 500 mg); either 64 of the small size (2 mm diameter x 2 mm thickness), sixteen of the medium size (4 mm x 2 mm) or one of the large size (15 mm x 2 mm) were obtained from cement bulk powder containing tetracalcium phosphate, dicalcium phosphate dihydrate and hydroxyapatite. In vitro IMC release from the 1, 2 and 5% drug-loaded apatite cement systems in simulated body fluid (SBF) (pH 7.25) at 37 degrees C increased with increasing concentrations of IMC and with decreasing geometrical size of the cement. The plots of in vitro IMC release per unit area against the square root of time increased with increasing IMC concentrations, but not with decreasing geometrical size of the cement. After subcutaneous (s.c.) implantation of differently sized 1% IMC-loaded cements in male Wistar rats, the plasma IMC concentration and the area under the curve increased with decreasing cement diameter. The in vivo IMC release profiles of the cement were deconvoluted from the plasma IMC profiles after s.c. administration of IMC solution. The plots of in vivo IMC release per unit area against the square root of time suggested that the initial release from all 1% drug-loaded cements was very rapid, slowed after one day, but continued for over two weeks. The relationship between the in vitro release in SBF and the in vivo release in rats of IMC-loaded cements was linear.

Animals↗
PubMed1998

Association study of structural mutations of the tyrosine hydroxylase gene with schizophrenia and Parkinson's disease.

Tyrosine hydroxylase (TH) gene is the rate-limiting enzyme in the synthesis of catecholamines. Functional polymorphisms of the TH gene may be involved in the pathogenesis of neuropsychiatric diseases such as schizophrenia, affective disorders, and Parkinsonism. This study examined a possible association of two polymorphisms, both of which result in an amino acid change of the TH protein, with schizophrenia and Parkinson's disease (PD). The Val81Met polymorphism is a common variation, although its effect on the enzyme expression is unclear. Leu205Pro polymorphism is a rare mutation that is reported to cause Parkinsonism in infancy for individuals who are homozygous for the mutated type. We genotyped a Japanese sample of 194 schizophrenics, 99 patients with PD, and 161 controls for the Val81Met polymorphism by using mis-match PCR and digestion by the restriction enzyme BalI. There was no significant allelic or genotypic association of the Val81Met polymorphism with schizophrenia or PD. The Leu205Pro polymorphism was examined by using PCR and digestion by AluI; however, there was no individual who carried the mutated type of Pro205 among 50 schizophrenics or 50 patients with PD. Thus we obtained no evidence for the involvement of the two structural mutations of the TH gene in the pathogenesis of schizophrenia or PD.

Alleles↗
PubMed1998

Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5).

A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line. The sequence analysis revealed that the cDNA encoded a protein of 557 aa residues with a calculated molecular weight of 64,236. The encoded protein has typical structural characteristics shown in the TRAF family of proteins and binds to the cytoplasmic region of lymphotoxin-beta receptor more efficiently than to that of CD40 and CD30. The TRAF5 gene was mapped to the human chromosome 1q32.3-q41.1. Overexpression of human TRAF5 activates NF kappa B transcription factor in human 293T kidney cells. These results suggest that the human TRAF5 protein could be involved in the signal triggered by various members of the tumor necrosis factor receptor (TNFR) superfamily including CD40, CD30 and lymphotoxin-beta receptor.

Amino Acid Sequence↗
PubMed1998

Pharmacological profiles of new orally active nonpeptide tachykinin NK1 receptor antagonists.

Pharmacological profiles of new orally active amide-based tachykinin NK1 receptor antagonists, N-[3,5-bis(trifluoromethyl)benzyl]-5-(4-fluorophenyl)-7,8-dihydro-N,7-di methyl-8-oxo-1,7-naphthyridine-6-carboxamide (referred to as compound I) and two related compounds (compounds II and III), were compared with that of (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), another nonpeptide tachykinin NK1 receptor antagonist. Compounds I, II, III and CP-99,994 caused parallel rightward shifts of the concentration-response curve of substance P in the guinea-pig ileum pretreated with atropine, mepyramine and indomethacin, with the pA2 values of 8.70, 7.56, 8.41 and 8.27, respectively. These antagonists did not alter the concentration-response curve of acetylcholine in the guinea-pig ileum nor that of neurokinin A in the rat vas deferens. Furthermore, contractile responses to senktide of the rat portal vein were not affected by these antagonists. In the isolated neonatal gerbil spinal cord pretreated with tetrodotoxin, substance P produced a dose-dependent depolarization of ventral roots. Compounds I, II, III and CP-99,994 caused parallel rightward shifts of the concentration-response curve of substance P in the spinal cord with the pA2 values of 7.07, 5.93, 6.40 and 7.26, respectively. In contrast, these antagonists did not affect the concentration-response curve of L-glutamate. These results suggest that compounds I, II and III are selective antagonists for tachykinin NK1 receptor both in peripheral tissues and the central nervous system.

Administration, Oral↗
PubMed1998

One-stage repair of interrupted aortic arch and aortopulmonary window.

Interrupted aortic arch type A with aortopulmonary window was diagnosed in a 12-day-old neonate. A successful one-stage repair was undertaken through a midline sternotomy without circulatory arrest. The aortopulmonary window was closed through the anterior wall of communication between ascending aorta and main pulmonary artery with a patch. Position of the arterial cannula was changed during the repair, which made it possible to mobilize and expose the aortic arch for the completion of direct anastomosis.

Aorta, Thoracic↗
PubMed1998

Effects of a tachykinin NK3 receptor antagonist, SR 142801, studied in isolated neonatal rat spinal cord.

Effects of a nonpeptide tachykinin NK3 receptor antagonist, SR 142801, were studied in the isolated spinal cord preparation of the neonatal rat. Potential changes were recorded extracellularly from a lumbar ventral root. Bath-application of neurokinin B induced a dose-dependent depolarization of the ventral root. SR 142801 caused rightward shifts of the concentration-response curve for neurokinin B with pA2 of 6.57, but did not affect the depolarizing responses to other agonists. Stimulation of a dorsal root evoked in the ipsilateral ventral root of the same segment monosynaptic and polysynaptic reflexes of fast time course which were followed by a slow depolarization (ipsilateral slow ventral root potential). SR 142801 depressed the ipsilateral slow ventral root potential. The present results indicate that SR 142801 is a specific antagonist for tachykinin NK3 receptors in the spinal cord and suggest that NK3 receptors are involved in primary afferent-evoked nociceptive responses of spinal neurones.

Animals↗
PubMed1998

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat.

1. Effects of wortmannin, an inhibitor of myosin light chain kinase, on the release of substance P and amino acids, GABA and glutamate, were investigated in the isolated spinal cord preparation of the neonatal rat. 2. Wortmannin at 0.5 - 10 microM depressed the release of substance P evoked by high-K+ (90 mM) medium from the spinal cord (IC50 = 1.1 microM). Wortmannin also depressed the high-K+ (70 mM)-evoked release of substance P from cultured dorsal root ganglion neurons of neonatal rats. In contrast, the high-K+ (90 mM)-evoked release of GABA and glutamate from the spinal cord was not affected by wortmannin (0.1 - 10 microM). 3. Upon stimulation of a dorsal root, a monosynaptic reflex and a subsequent slow ventral root depolarization were evoked in the ipsilateral ventral root of the same segment in the isolated spinal cord preparation. The magnitude of the slow ventral root depolarization was depressed gradually to about 70% of the control during the course of 30 min under wortmannin (1 microM). In contrast, the monosynaptic reflex was unaffected by wortmannin. 4. Immunofluorescent staining revealed that immunoreactivities of substance P and myosin II were colocalized at presynaptic terminals in the dorsal horn of the neonatal rat spinal cord. 5. The present results suggest that myosin phosphorylation by myosin light chain kinase may play a crucial role in the release of substance P, but not in the release of GABA and glutamate in the neonatal rat spinal cord. This may reflect a difference in the exocytic mechanisms of substance P-containing large dense core vesicles and amino acid-containing small clear vesicles.

Amino Acids↗
PubMed1998

Combined effects of laser irradiation/solution fluoride ion on enamel demineralization.

OBJECTIVE: The effects of CO2 laser irradiation of dental enamel were evaluated in enamel demineralization experiments in partially saturated solutions (i.e., solutions containing both calcium and phosphate ions) with and without fluoride ions. SUMMARY BACKGROUND DATA: Previous studies had shown that a continuous-wave CO2 laser at an energy density of around 130 J/cm2 may induce an increased acid resistance in human dental enamel as assessed by exposure to severe demineralization conditions (0.1 mol/L acetate buffer, pH 4.5 and ionic strength 0.5 mol/L). METHODS: Enamel blocks were irradiated with a continuous-wave CO2 laser at a wavelength of 10.6 microns using energy densities of from 42.5 to 170.0 J/cm2. The blocks were then exposed to a partially saturated demineralizing solution with or without 0.2 ppm fluoride at a temperature of 30 degrees C for 24 hours. The demineralization was examined both qualitatively by light microscopy and quantitatively by microradiography. RESULTS: A comparison between the lased and the unlased portions of enamel showed increased acid-resistance with increasing laser energy density and, at the highest energy density of 170.0 J/cm2, there was little or no lesion development in the fluoride-free dissolution medium. The demineralization of enamel was reduced dramatically in the presence of 0.2 ppm fluoride for both lased and unlased enamel; there was only modest lesion development observed for unlased enamel and, at an energy density as low as 85.0 J/cm2, the surface of enamel was found to be completely protected. CONCLUSIONS: These findings are consistent with the mechanism that laser irradiation of dental enamel results in significant reduction of the effective solubility of enamel mineral and that there is a significant synergism between laser irradiation and solution fluoride with regard to this effect.

Carbon Dioxide↗
PubMed1998

Postoperative chemotherapy may improve prognosis in unresectable gastric cancer.

We have retrospectively evaluated to prognosis of patients with unresectable gastric cancer (UGC) and the effect of postoperative chemotherapy on that prognosis. One hundred patients who died of UGC included 37 patients who received postoperative chemotherapy (chemotherapy group) and 63 patients who did not receive postoperative chemotherapy (control group). Chemotherapy regimens were as follows: intravenous mitomycin (MMC) plus 5-fluorouracil (5-FU) (n=15), oral 5-FU alone (n=10), intravenous methotrexate (MTX) plus 5-FU (n=8), intravenous cisplatin plus 5-FU (n=2), and hepatic arterial infusion of 5-FU plus oral 5-FU (n=2). No prior chemotherapy or radiation therapy was given. All patients' cancers were stage IV. Median survival of the chemotherapy group (238 days) was significantly longer than the control group (137 days). The 1-year survival rate in the treated group was 19.0% but only 2.4% in the control group (p < 0.01). Patients with palliative gastrojejunostomy did not survive significantly longer than those having laparotomy alone or ileal tube insertion. We conclude that the prognosis for patients with UGC remains very poor, but postoperative chemotherapy may contribute to prolonged survival in patients with UGC.

Adenocarcinoma↗
PubMed1998

Induction of apoptosis in human pancreatic carcinoma cells by a synthetic bleomycin-like ligand.

Histidine-pyridine-histidine-3 (HPH-3) is an oxygen-activating ligand based on the structure of bleomycin. HPH-3 induced the death of human pancreatic adenocarcinoma AsPC-1 cells in 24 h, causing apoptotic morphology and internucleosomal degradation of DNA. HPH-3-induced cell death was not inhibited by antioxidants such as reduced glutathione and N-acetylcysteine, whereas hydrogen peroxide-induced cell death was inhibited by them, indicating that hydrogen peroxide is not involved in the induction of apoptosis by HPH-3. Induction of apoptosis by HPH-3 was inhibited by zinc and copper ions, indicating that chelation with ferrous ion is responsible for induction of apoptosis, as is the case in chelation by bleomycin to cleave DNA. Bleomycin A2 and its fragment having no DNA-binding region, glycopeptide-3, did not induce apoptosis in AsPC-1 cells. Bleomycin A2 induced G2/M block in flow-cytometric analysis, but HPH-3 did not and instead induced an apoptotic pre-G1 peak. Thus, HPH-3 induced apoptosis in human pancreatic carcinoma cells, which is a unique characteristic among bleomycin-related compounds.

Adenocarcinoma↗
PubMed1998

Effects of ethanol, acetoin and 2,3-butanediol on EEG power spectra in conscious rats.

Effects of ethanol, acetoin and 2,3-butanediol on the central nervous system (CNS) were investigated by using the analysis of EEG (electroencephalogram) spectral powers recorded at the frontal cortex in rats. High doses of ethanol were required for exhibiting an increase of EEG spectral powers in the delta (0-4 Hz) and theta (4-8 Hz) waves when it was given either orally or intravenously. On the other hand, when ethanol was injected intracerebroventricularly, the drug caused a potent increasing effect of EEG spectral powers. Both acetoin and 2,3-butanediol were found to increase in EEG spectral powers by oral and intravenous administrations at relatively low doses. In addition, acetoin and 2,3-butanediol were more effective than ethanol in increasing EEG spectral powers in the delta and theta bands after intracerebroventricular administration. From these findings it can be concluded that both acetoin and 2,3-butanediol have a potent CNS depressant effect.

Acetoin↗
PubMed1998

Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of guinea pigs.

We studied the effect of morphine on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea pigs, by use of the whole-cell patch clamp technique. Morphine inhibited 30 microM glycine-induced current (Igly), without affecting the current caused by 30 microM GABA. The effect of morphine was concentration-dependent, with a maximal effect at 1 mM, and reversible. The half-maximum inhibitory concentration of morphine was 30 microM. The effect of morphine was not depressed by naloxone, an opioid antagonist. Furthermore, the effect was not substantially affected by methiothepin, a 5-HT1 antagonist, ketanserin, a 5-HT2 antagonist and MDL-72222, a 5-HT3 antagonist. Morphine at 30 microM shifted the concentration-response curve for Igly to the right without affecting the maximum value. The effect of morphine on Igly showed no use-dependence. The results indicate that morphine inhibits Igly in the NTS neurones, and further suggest that morphine at the concentration used may act on the glycine receptor-ionophore complex, but not on the Cl-channel of the complex.

Animals↗