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Biomedical subjects

K Hatanaka

Publications and source records attributed to K Hatanaka.

At least 73 records · Page 4Linked to original sources
PubMed1998

Neurochemical and behavioral characterization of potential antidepressant properties of indeloxazine hydrochloride.

The potential antidepressant properties of indeloxazine hydrochloride were examined in vitro and in vivo. Indeloxazine showed preferential affinity for both [3H] citalopram (Ki: 22.1 nM) and [3H]nisoxetine binding sites (Ki: 18.9 nM) in membranes of the rat cerebral cortex. In microdialysis studies, intraperitoneal injection of indeloxazine (3 and 10 mg/kg) dose-dependently increased the extracellular level of both serotonin and norepinephrine in rat frontal cortex of freely moving rats. Amitriptyline was almost equivalent to indeloxazine in these two assays with the exception of a much weaker effect on extracellular serotonin levels. Spontaneous [3H]serotonin release from rat cortical synaptosomes was significantly enhanced by indeloxazine (10-1000 nM). In behavioral studies, indeloxazine increased the number of wheel rotations in forced swimming tests in both ICR mice (50 mg/kg, p.o.) and SAMP8//YAN, a substrain of senescence-accelerated mouse (20 and 30 mg/kg, p.o.). Indeloxazine (3-10 mg/kg p.o.) also inhibited the incidence of muricide in raphe-lesioned rats. These results suggest that indeloxazine is an inhibitor of serotonin and norepinephrine uptake and has potential antidepressant properties. In addition, the drug-induced enhancement of serotonin release may contribute to its potent effects on the serotonergic system in vivo.

Amitriptyline↗
PubMed1998

Differing profiles of prostaglandin formation inhibition between selective prostaglandin H synthase-2 inhibitors and conventional NSAIDs in inflammatory and non-inflammatory sites of the rat.

The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

Hemispheric asymmetry of the auditory evoked N100m response in relation to the crossing point between the central sulcus and Sylvian fissure.

The positions of the bilateral N100m sources of the auditory evoked magnetic fields (AEFs) were measured in relation to the central sulcus (CS) using an MRI-linked whole head magnetoencephalography system in 20 right-handed normal male subjects. The location of the N20m source of the median nerve-stimulated somatosensory evoked magnetic fields (SEFs), in the left hemisphere was 3.9+/-5.4 mm (mean+/-SD) posterior to that in the right hemisphere (P < 0.005). The crossing point (CP) between the CS and Sylvian fissure in the left hemisphere was 4.3+/-4.8 mm posterior to that in the right hemisphere (P < 0.001). The N100m sources were posterior to the CP in both hemispheres. The left hemispheric N100m source was 9.4+/-6.4 mm posterior to that on the right (P < 0.0001) in absolute position. The relative distance between CP and the N100m source was 22.7+/-8.5 mm in the left hemisphere and 17.7+/-5.3 mm in the right hemisphere (P < 0.01). Comparison of positions of the AEF sources and the CS as defined by the SEF demonstrated functional asymmetry of the human temporal lobe and possible source extension of the AEF-N100m beyond the Heschl gyrus over the planum temporale.

Adult↗
PubMed1998

[Interhemispheric asymmetry exists in female in the N100m source position of the auditory evoked magnetic fields].

The N100m source of the auditory evoked magnetic fields (AEFs) is located more posterior in the left than the right hemisphere in male subjects. However, whether this asymmetry exists in female subjects is controversial. The present study, analyzed the N100m source positions of the AEFs due to monaural tone stimuli using a helmet-shaped 66-channel magnetoencephalography system (CTF Systems) in 62 right-handed normal adults (24 females and 38 males). The best fit sphere was calculated for each subject from the head shape reconstructed from three-dimensional magnetic resonance images. N100m source positions were estimated using a double-dipole model. The contralateral N100m response to the stimulated ear was measured relative to the midpoint of the bilateral auricular points. Statistical analysis used a standardized head size for each subject based on the mean value of all subjects (r = 8.27 cm). In females, the N100m dipole positions were 0.00 +/- 1.02 cm anterior in the left hemisphere and 0.35 +/- 0.74 cm in the right (p < 0.02). In males, the N100m dipole positions were -0.31 +/- 0.81 cm (mean +/- standard deviation) anterior in the left hemisphere and 0.61 +/- 0.78 cm in the right (p < 0.0001). The interhemispheric difference in the N100m positions was 0.35 +/- 0.65 in females and 0.92 +/- 0.77 in males (p < 0.005). In conclusion, the left hemispheric N100m is located more posterior to the right in both genders. However, this functional asymmetry is more evident in males, like previous findings of more evident anatomical asymmetry in males.

Adult↗
PubMed1997

Auditory evoked magnetic fields in patients with right hemisphere language dominance.

Auditory evoked magnetic fields for pure-tone stimuli were measured in seven subjects with right hemisphere dominance for language using a whole-head magnetoencephalography system linked to magnetic resonance imaging. N100m responses were observed in both hemispheres in five subjects. The N100m response latency to contralateral stimulation was significantly shorter on the right than on the left in all cases. Normal right-handed subjects with left hemisphere dominance showed exactly the same responses. Therefore, the shorter N100m latency in the right hemisphere is independent of the dominant hemisphere for language.

Acoustic Stimulation↗
PubMed1997

Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity.

YM992 ((S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride) is a novel compound that has selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT2A receptor antagonistic activity in vivo. YM992, fluoxetine and citalopram showed 5-HT uptake inhibition activity in l-5-hydroxy-tryptophan (l-5-HTP)-treated mice. YM992 and trazodone attenuated 5-HT2A/2C receptor agonist-induced head-twitches in mice, indicating that these drugs had 5-HT2A receptor antagonistic activity. YM992 and amitriptyline were highly active in the mouse tail suspension test. In contrast, fluoxetine and citalopram showed only a tendency to reduce the immobility time. Single treatment with YM992 as well as trazodone and fluoxetine ameliorated the learning deficit of olfactory-bulbectomized rats, whereas citalopram and amitriptyline showed an ameliorative effect only after chronic treatment. Although YM992 has moderate affinity for alpha1-adrenoceptors, alpha1-adrenoceptor antagonism of YM992 in vivo was 10 times weaker than that of trazodone. These results demonstrate that YM992 has 5-HT uptake inhibition and 5-HT2A receptor antagonistic activity in vivo, and suggest that YM992 may be a novel antidepressant with high efficacy in clinical use.

Animals↗
PubMed1997

Comparison of radiobiological effective depths in 65-MeV modulated proton beams.

To assess the achievement of uniformity of radiobiological effectiveness at different depths in the proton spread-out Bragg peak (SOBP), Chinese hamster ovary (CHO) cells were exposed to 65-MeV modulated proton beams at the Research Center for Nuclear Physics (RCNP) of Osaka University. We selected four different irradiation positions: 2 mm depth, corresponding to the entrance, and 10, 18 and 23 mm depths, corresponding to different positions in the SOBP. Cell survival curves were generated with the in vitro colony formation method and fitted to the linear-quadratic model. With 137Cs gamma-rays as the reference irradiation, the relative biological effectiveness (RBE) values for a surviving fraction (SF) level of 0.1 are 1.05, 1.10, 1.12 and 1.19 for depths of 2, 10, 18 and 23 mm respectively. A significant difference was found between the survival curves at 10 and 23 mm (P < 0.05), but not between 18 and 10 mm or between 18 and 23 mm. There was a significant dependence of RBE on depths in modulated proton beams at the 0.1 surviving fraction level (P < 0.05). Moreover, the rise of RBEs significantly depended on increasing SF level or decreased approximately in correspondence with irradiation dose (P = 0.0001). To maintain uniformity of radiobiological effectiveness for the target volume, careful attention should be paid to the influence of depth of beam and irradiation dose.

Animals↗
PubMed1997

Purification and characterization of endo-beta-N-acetylglucosaminidase from hen oviduct.

Endo-beta-N-acetylglucosaminidase from hen oviduct (Endo-HO) was purified to homogeneity by ammonium sulfate fractionation and then by column chromatographies on DEAE-Sephacel, hydroxyapatite, Octyl-Sepharose CL-4B, Co2+-chelating Sepharose FF, and YMC-Pack Diol-200G. Partial purification of the enzyme was reported previously [Tarentino, A.L. and Maley, F. (1976) J. Biol. Chem. 251, 6537-6543]. The molecular weight was 54,000 by gel filtration and 52,000 by SDS-PAGE in the presence of 2-mercaptoethanol, indicating that Endo-HO is composed of a single polypeptide chain. The optimum pH was 6.5, and the Km value was 25 microM when pyridylaminated Man6GlcNAc2 was used as a substrate. EDTA and metal cations tested, except Hg2+, had no effects on Endo-HO activity. Substrate specificity results using pyridylaminated N-linked sugar chains revealed that Endo-HO hydrolyzed oligomannose-type sugar chains faster than complex- and hybrid-type chains, and that sugar chains containing the Manalpha1-2Manalpha1-3Manbeta1-4GlcNAcbeta1-GlcN Ac structure were good substrates for the enzyme. These findings suggest that in cytosol the enzyme contributes to the production of a free oligosaccharide with one reducing end N-acetylglucosamine residue in cooperation with neutral alpha-mannosidase, an enzyme that specifically hydrolyzes oligosaccharides to Manalpha1-2Manalpha1-2Manalpha1-3(Manalpha1-6)++ +Manbeta1-4GlcNAc.

Animals↗
PubMed1997

Evaluation of pharmacological profile of meloxicam as an anti-inflammatory agent, with particular reference to its relative selectivity for cyclooxygenase-2 over cyclooxygenase-1.

We studied the anti-inflammatory activity of meloxicam on rat carrageenin-induced pleurisy and its toxicity for rat gastric mucosa, relative to its in vitro inhibitory potency against partially purified cyclooxygenase (COX)-1 and COX-2 preparations in order to clarify the pharmacological profile of the compound as an anti-inflammatory agent. In rat carrageenin-induced pleurisy, the plasma exudation rate peaked at 5 h, at which time COX-2 was detectable in cells from the pleural exudate. Meloxicam and piroxicam (1 and 3 mg/kg) and NS-398 (3 mg/kg) showed almost equal anti-inflammatory potency against 5-hour pleurisy. A single oral administration of the compounds caused a dose-dependent increase in the number of rats with gastric mucosal erosion. The ED50 value for meloxicam (5.92 mg/kg) was significantly higher than that for piroxicam (1.76 mg/kg), indicating that meloxicam is safer. Indometacin showed intermediate safety (2.59 mg/kg). In in vitro experiments, indometacin inhibited COX-1 about 1.7 times more potently than COX-2. NS-398 inhibited COX-2 with an IC50 of 0.32 microM, but never affected COX-1 activity, even at 100 microM. In the same assay system, meloxicam inhibited COX-2 about 12 times more selectively than COX-1. Piroxicam, however, inhibited both isoforms almost equally. These results indicate that meloxicam is a potent anti-inflammatory agent with low gastric toxicity. One reason for its in vivo pharmacological profile may be related to its relative selectivity for COX-2 over COX-1. Thus, meloxicam may belong to a group of COX-2 selective anti-inflammatory agents with a better safety profile than conventional COX-1 and COX-2 nonselective anti-inflammatory agents.

Administration, Oral↗
PubMed1997

Significant roles of inducible cyclooxygenase (COX)-2 in angiogenesis in rat sponge implants.

Angiogenesis in rat sponge implants, as determined from the concentration of hemoglobin in the sponge granuloma tissues, was gradually increased over a 14-day experimental period. The inducible cyclooxygenase COX-2 was detected in the sponge granuloma tissues at day 4 by Western blot analysis using specific mouse COX-2 antibody. Angiogenesis in the sponge implants was enhanced by daily topical injections of human recombinant basic fibroblast growth factor (bFGF) or human recombinant epidermal growth factor (EGF) (100 or 1000 ng/sponge/day) for 4 days. These treatments clearly enhanced the expression of COX-2 in the sponge granuloma tissues. In immunohistochemical studies, COX-2-positive staining was mainly observed in the endothelial cells of the neovasculature and in the fibroblasts of the granuloma capsule. Administration of the selective COX-2 inhibitor NS-398 (p.o., 3 mg/kg, 3 times a day) for 14 days significantly inhibited the angiogenesis. The angiogenesis enhanced with bFGF or EGF (day 4) was inhibited by administration of indomethacin or NS-398, both in the above regimen, and fell to the level obtained without growth factor treatment. These results suggest that COX-2 induced in the sponge granuloma tissues may participate in neovascularization through prostaglandin formation.

Animals↗
PubMed1997

Striate cortical generators of the N75, P100 and N145 components localized by pattern reversal visual evoked magnetic fields.

Magnetic fields evoked by checkerboard pattern reversal visual stimulation to the monocular left or right half-field were recorded over the whole head using a helmet-shaped 64 channel magnetoencephalography system in fourteen normal subjects. The sources of the triphasic N75m-P100m-N145m responses were located using a single current dipole model. Relative locations and orientations of the N75m and N145m dipoles to the P100m dipole were calculated for each subject to reduce errors due to 'anatomical variability and then averaged for all subjects under the same stimulus conditions. These averaged parameters showed that N75m and N145m originated from the same location in the striate cortex as P100m and reversed their orientations successively by 180 degrees during the time course.

Adult↗
PubMed1997

[Postoperative normalization of prolonged P100m latency in the visual evoked magnetic field in a patient with occipital meningioma].

A 49-year-old female with a left occipital parasagittal meningioma was found to have prolonged P100m latency of the pattern reversal visual evoked magnetic field only in the hemisphere containing the lesion. After total removal of the tumor, the P100m latency was normalized in the affected hemisphere. Based on current dipole models, all the P100m dipoles were localized at the lateral bottom of the calcarine fissures bilaterally, as indicated by our previous study with normal subjects. Since the tumor was located near the parietoocipital sulcus and distant from the primary visual cortex, disturbance of the higher visual cortex probably affected the P100m latency.

Brain Mapping↗
PubMed1997

Structural analysis of nucleic acids by using fluorescence resonance energy transfer (FRET).

We examined changes in the extent of fluorescence resonance energy transfer (FRET) between two different fluorochromes attached to a single oligonucleotide in the presence or absence of target nucleic acids with a specific sequence and a higher-ordered structure. In our system, FRET was maximal when probes were free in solution and a decrease in FRET was evidence of successful hybridization. Incubation of the probe with a single-stranded complementary oligonucleotide reduced the FRET. While, a small change in FRET was also observed when the probe was incubated with an oligonucleotide in which the target site had been embedded in a stable hairpin structure. These results indicate that this spectrofluorometric method and FRET probes can be used to estimate the efficacy of hybridization between a probe and its target site within highly ordered structures. It should help us to estimate the suitability of designed functional molecules, such as antisense DNA and RNA and ribozymes, that target to specific sites.

DNA↗
PubMed1996

Selective determination of haloperidol in human serum: surface ionization mass spectrometry and gas chromatography with surface ionization detection.

Surface ionization organic mass spectrometry (SIOMS) has been performed on the clinically important drug haloperidol using quadrupole mass spectrometry in which the thermal ion source has a rhenium oxide emitter. The surface ionization (SI) mass spectrum is presented, interpreted in a purely empirical way by means of evidence from previous investigations, and then compared to results from conventional electron impact (EI) ionization. An approach to detection of this drug in serum by gas chromatography (GC) with a surface ionization detector (SID) and GC-SIOMS is described. This approach demonstrates that (a) haloperidol is efficiently surface-ionized, giving a unique SI mass spectrum, (b) experimental results rationalize the combined sensitivity and selectivity of the GC-SID for the examined drug, (c) the detection limit for haloperidol in serum is 1.1 ng/ml (S/N = 3) by GC-SID (the coefficients of variation of the assay are generally low, i.e., below 8.5%) and (d) the GC-SIOMS coupling can be used for sensitive and selective detection of haloperidol in serum.

Chromatography, Gas↗
PubMed1996

Gustatory evoked magnetic fields in humans.

Magnetic fields evoked by taste stimuli of the human tongue were measured over the whole head using a helmet-shaped 64 channel magnetoencephalography system in five normal subjects. The stimuli were 10% glucose and 0.3 M NaCl solutions and distilled water. The most prominent peak (N175m) appearing over the bilateral hemispheres had a latency of 150-210 ms. The N175m sources were located using a two-dipole model in a spherical conducting medium based on the individual head dimensions and superimposed on magnetic resonance images. The N175m dipoles due to 10% glucose and 0.3 M NaCl stimuli were located at the operculum and circum-insular areas in both hemispheres, but those due to distilled water could not be located accurately.

Adult↗
PubMed1996

Increased migration of neutrophils to granulocyte-colony stimulating factor in rat carrageenin-induced pleurisy: roles of complement, bradykinin, and inducible cyclooxygenase-2.

Administration of human recombinant granulocyte colony-stimulating factor (G-CSF, 100 micrograms/kg/day, s.c) to rats for 4 days significantly increased circulating neutrophil counts (by 1130%), together with an increase in mononuclear leukocyte counts (by 119%). Infiltrated pleural neutrophil counts in G-CSF-treated rats (G-CSF-r) 5 h after the intrapleural injection of zymosan-activated serum were significantly higher (by 155%) than those in control rats (Vehicle-r). In carrageenin-induced pleurisy, counts of infiltrated pleural neutrophils in G-CSF-r 5 and 7 h after carrageenin were significantly higher (by 119% and 116%) than those in Vehicle-r. G-CSF treatment increased the volume of pleural exudate and the plasma exudation rate by 122% and 226%, compared to values in Vehicle-r 5 h after carrageenin. Cobra venom factor (75 micrograms/kg, i.v.) significantly reduced pleural neutrophil migration in G-CSF-r (by 53%) and Vehicle-r (by 49%). Bromelain (10 mg/kg, i.v.) and aspirin (100 mg/kg, p.o.) reduced pleural neutrophil migration and reduced exudate volume and plasma exudation. Intrapleural bradykinin-(1-5) and prostaglandin E2 levels were significantly higher in G-CSF-r than in Vehicle-r. The increased neutrophil migration in G-CSF-r may be attributed to enhanced activation of the complement system facilitated by increased plasma exudation due to bradykinin and prostaglandins.

Animals↗
PubMed1996

Role of prostaglandin H synthase-2 in prostaglandin E2 formation in rat carrageenin-induced pleurisy.

Rat carrageenin-induced pleurisy was used to clarify the role of prostaglandin H synthase (PGHS)-2 in acute inflammation. Intrapleural injection of 0.2 ml of 2% lambda-carrageenin induced accumulation of exudate and infiltration of leukocytes into the pleural cavity. When PGHS-1 and -2 proteins in the pleural exudate cells were analyzed by Western blot analysis, PGHS-2 was detectable from 1 hr after carrageenin injection. Its level rose sharply, remained high from 3 to 7 hr after injection, and then fell to near the detection limit. PGHS-1 was also detected, but kept almost the same level throughout the course of the pleurisy. Levels of prostaglandin (PG) E2 and thromboxane (TX) B2 in the exudate increased from hour 3 to hour 7, and then declined. Thus, the changes of the level of PGE2 were closely paralleled those of PGHS-2. The selective PGHS-2 inhibitors NS-398, nimesulide and SC-58125 suppressed the inflammatory reaction and caused a marked decrease in the level of PGE2 but not in those of TXB2 and 6-keto-PGF 1 alpha. These results suggest that the PGHS-2 expressed in the pleural exudate cells may be involved in PGE2 formation at the site of inflammation.

6-Ketoprostaglandin F1 alpha↗