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T Kida

Publications and source records attributed to T Kida.

At least 19 recordsLinked to original sources
PubMed2003

Metabolite analysis of [11C]Ro15-4513 in mice, rats, monkeys and humans.

We performed in vitro and in vivo assays of the metabolism of [(11)C]Ro15-4513 over time in the plasma of mice, rats, monkeys and humans, using a radio-HPLC equipped with a sensitive positron detector, in order to compare the metabolic rates of the radiopharmaceutical agent among the different animal species and to establish a highly sensitive analytical method for the radiotracer agent. We also examined the metabolism of [(11)C]Ro15-4513 in the brain tissue of mice and rats. The analytical method used in this study permitted detection of even extremely low levels of radioactivity (approximately 5,000 dpm). In vitro experiments revealed that [(11)C]Ro15-4513 in the blood was metabolized to hydrolysate [(11)C]A. The species were classified in descending order of the metabolic rate of the radiotracer in vitro as follows; mice, rats, and monkeys/humans. In the in vitro experiment, the percentage of the unchanged drug in the plasma at 60 minutes postdose was 9% in mice, 70% in rats, 97% in monkeys, and 98% in humans. In vivo metabolite analysis in the blood showed the presence of two radioactive metabolites, consisting of one hydrolysate [(11)C]A and another unidentified substance. The species were classified in descending order of the metabolic rate of the radiotracer in vivo as follows; mice, rats/humans, and monkeys. The percentage of the unchanged drug in the plasma was 6% in mice, 21% in rats, 26% in humans, and 40% in monkeys. Furthermore, the in vitro and in vivo experiments conducted to analyze the metabolism of [(11)C]Ro15-4513 in the brain tissue of mice and rats revealed that the radiotracer was metabolized to some extent in the brain tissue of these animals. In the in vivo experiment, the percentage of the unchanged drug at 60 min postdose was 86% in the brain tissue of mice and 88% in the brain tissue of rats, while in the in vitro experiment, the corresponding percentage was 93% in mice, and 91% in rats.

Animals↗
PubMed2002

The proportion of cells with functional X disomy is associated with the severity of mental retardation in mosaic ring X Turner syndrome females.

Turner syndrome females (45,X) do not have mental retardation (MR), whereas some mosaic ring X Turner syndrome females, with 45,X/46,X,r(X), have severe MR. The MR is believed to be caused by a failure of X chromosome inactivation (XCI) of the small ring X chromosome, which leads to functional X disomy (FXD), To explore this hypothesis, we examined the proportion of FXD cells in the peripheral blood of four ring X Turner syndrome females with various levels of MR, using two newly developed XCI assays based on DNA methylation of X-linked genes. As a result, the two patients with extremely severe MR showed complete FXD patterns, whereas the remaining two patients with relatively milder MR showed partial FXD patterns. These results indicate that the proportion of FXD cells may be associated with the severity of MR in mosaic ring X Turner syndrome females, although this association should be confirmed by examining brain cells during development. One of the cases with severe MR and a complete FXD pattern neither lacked the XIST gene nor had uniparental X isodisomy, and we discuss the mechanism of the failure of XCI in this case.

Child↗
PubMed2001

Sensitive measurement of positron emitters eluted from HPLC.

For sensitive analysis of the radioactive-metabolite in human PET, a radio-HPLC system coupled to a newly designed positron detector was constructed. The detector had the advantages of low noise level (1.7 +/- 1.0 cpm) and high sensitivity (32 +/- 1%) due to coincidence counting and large BGO crystals. Furthermore, the detector was easy to move, since a pair of the BGO housings coupled to photomultipliers was effectively arranged in parallel and a HPLC cell with different volume could be inserted between the BGO housing. This radio-HPLC system was useful for analyzing samples with low radioactivity. It was applied to the measurement of [11C]FLB457 in plasma, having high affinity and high selectivity with dopamine D2 receptors. Extremely low radioactivity of [11C]FLB457 (2500 dpm) could be analyzed by using the radio-HPLC system. The performance of this detector was compared with those of commercially available systems that had been used as sensitive detectors for HPLC.

Animals↗
PubMed2001

The mechanism and change in the optic nerve head (ONH) circulation in rabbits after glucose loading.

PURPOSE: To assess the influence of the blood glucose level on ocular capillary circulation, we induced clinically significant hyperglycemia (200--300 mg/dl) in rabbits and investigated the changes in the optic nerve head (ONH) circulation. METHODS: Hyperglycemia was induced by injection of glucose (5.6 mmol/kg) into an auricular vein of healthy albino rabbits and changes in the ONH circulation were measured by the laser speckle method. In order to examine the role of nitric oxide (NO), glucose was administered after intravenous injection of an NO synthetase inhibitor (N(G)-nitro-L-arginine methyl ester, L-NAME, 1 mg/kg), then changes in the ONH circulation were measured. RESULTS: The blood glucose level reached a peak at 30 min after glucose loading and returned to its initial level by 2 hours. ONH circulation showed a 60% increase compared with its initial level at 15 min after glucose loading and subsequently remained almost unchanged throughout the 2-hour observation period. There were no significant changes of the blood pressure, heart rate, or intraocular pressure. The glucose-induced increase of ONH circulation was completely inhibited by pretreatment with L-NAME. CONCLUSIONS: ONH circulation was increased by administration of glucose to healthy rabbits. A high blood glucose level seems to promote ocular capillary circulation and NO as well as insulin appear to have a role in this process.

Animals↗
PubMed2001

The effect of nipradilol, an alpha-beta blocker, on retinal blood flow in healthy volunteers.

PURPOSE: To study the effects of topically applied nipradilol, an alpha-beta blocker recently developed in Japan as an ocular hypotensive drug, on retinal blood flow (RBF) in healthy volunteers. METHODS: Seven healthy volunteers (mean age, 33 years) underwent measurement of RBF using a newly developed stabilized laser Doppler velocimetry system. In a double-blind trial, retinal arterial blood flow, intraocular pressure (IOP), and blood pressure (BP) were measured before and after the instillation of nipradilol or saline every hour for 5 hours. RESULTS: Retinal arterial blood flow and the diameter of the retinal artery significantly (p< 0.05) increased at 4 hours after instillation in nipradilol-treated eyes. Retinal blood velocity did not change significantly. Nipradilol evoked a significant (p< 0.05) bilateral decrease in IOP. Mean BP decreased significantly (p< 0.05) 3 hours after instillation. Ocular perfusion pressure (OPP), calculated from the mean BP and IOP, did not change significantly during the study. CONCLUSION: Topical nipradilol significantly increased retinal arterial blood flow in healthy volunteers, not through a secondary effect dependent on a change in OPP, but likely through the vasodilatory action of the drug.

Adrenergic alpha-Antagonists↗
PubMed2001

Involvement of nitric oxide in the ocular hypotensive action of nipradilol.

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.

Administration, Topical↗
PubMed2001

Possible involvement of endothelin-1 and nitric oxide in the pathogenesis of proliferative diabetic retinopathy.

BACKGROUND: Overproduction of endothelin-1 (ET-1) and nitric oxide (NO) in the retina is demonstrated in experimental diabetic animals. To clarify the possible involvement of ET-1 and NO in the pathogenesis of diabetic retinopathy, the authors examined the vitreous levels of these principal endothelium-derived vasoactive substances in patients with proliferative diabetic retinopathy (PDR). METHODS: Vitreous fluid was taken from patients with PDR (ET-1, n = 12; NO, n = 12) and from patients with macular holes as controls (ET-1, n = 10; NO, n = 10) at vitreous surgery. Endothelin-1 and NO metabolites were measured by radioimmunoassay and high-performance liquid chromatography based on the Griess method, respectively. RESULTS: Endothelin-1 levels (mean +/- SE) were 21.5 +/- 1.7 pg/mL in the vitreous of patients with PDR and 16.7 +/- 0.7 pg/mL in the vitreous of patients with macular hole. There was a significant difference between patients with PDR and controls (P = 0.009, Mann-Whitney). Nitrate (NO3) was 49.8 +/- 5.0 micromol/L in patients with PDR and 24.2 +/- 2.8 micromol/L in patients with macula hole; it was also significantly elevated in patients with PDR (P = 0.004, Mann-Whitney), whereas nitrite (NO2) was not detected in this study. CONCLUSION: These results indicate that ET-1 and NO may be related in the pathogenesis of PDR.

Adult↗
PubMed2001

A prodrug of NMDA/glycine site antagonist, L-703,717, with improved BBB permeability: 4-acetoxy derivative and its positron-emitter labeled analog.

4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.

Animals↗
PubMed2000

Effect of competing alkali metal cations on neutral Host's anion binding ability

Anion binding by neutral hosts in organic solvents can be inhibited by the presence of alkali metal cations. The binding inhibition is due to salt ion-pairing which increases in the order Cs(+) < K(+) < Na(+). The binding inhibition can be reversed by using heteroditopic hosts that simultaneously bind both the metal cation and the anion. The largest cation-induced enhancements are observed with the less basic anions.

Journal Article↗
PubMed2000

Novel chiral bisoxazoline ligands with a biphenyl backbone: preparation, complexation, and application in asymmetric catalytic reactions

Novel C(2)-symmetric chiral bisoxazoline ligands 1 were easily prepared from enantiomerically pure 2-amino alcohols and achiral 2, 2'-biphenyldicarboxylic acid via the corresponding amide and mesylate as intermediates. Since these ligands bear only two ortho-substituents on the biphenyl backbone, the biphenyl axis is not fixed, and the two diastereomers of these ligands exist in equilibrium in solution. Interestingly, when the ligands 1 were coordinated with a metal ion, only one of the two possible diastereomer complexes, an (S,aS,S)-complex, can be formed depending on the combination of the ligand and the metal ion. Thus, copper(I) afforded only the (S,aS,S)-complexes with all ligands 1, while zinc(II), palladium(II), and silver(I) afforded the (S,aS, S)-complexes as the sole product only with 1b, which has a bulky tert-butyl group on the oxazoline ring, and a mixture of the two diastereomer complexes with 1a,c,d. The copper(I)-catalyzed asymmetric cyclopropanation of styrene with diazoacetate proceeded successfully with these ligands and good to excellent enantioselectivities were afforded.

Journal Article↗
PubMed2000

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding.

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [(11)C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [(11)C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors.

Animals↗
PubMed2000

Time-course changes of eosinophil counts in premature infants: no effects of medical manipulation, except erythropoietin treatment, on eosinophilia.

In order to determine the factors responsible for eosinophilia during the neonatal period, we counted the eosinophils of premature infants every week and compared the medical profiles of infants with eosinophil counts above the 95th percentile and those below that percentile during the course of study. Medical treatments such as mechanical ventilation, antibiotics administration and intravenous catheterization had no significant effects on the increase of eosinophils. Furthermore, the incidence of eosinophil counts above the 95th percentile was not different between breast-fed and formula-fed infants. The infants treated with erythropoietin had greater eosinophil counts than those with no treatment. It is probable that medical manipulation using foreign bodies such as intratracheal tube, intravenous catheter, antibiotics and artificial formula had no significant effects on the increase of eosinophil counts, except for exogenous erythropoietin.

Disease Progression↗
PubMed2000

Are high barometric pressure, low humidity and diurnal change of temperature related to the onset of asthmatic symptoms?

BACKGROUND: Meteorologic factors play a role in the expression of asthmatic symptoms; however, there are controversies about the causal relationship between meteorologic factors and asthma. The relationship between meteorologic parameters and emergency admissions for asthmatic symptoms in this hospital were analyzed. METHODS: A total of 205 patients (130 boys and 75 girls, 0.1-16.6 years of age) who were admitted to Hakodate Chuo General Hospital for asthmatic symptoms between 1 January and 31 December 1997 were submitted to our study. We divided a total of 365 days into two groups of days with and without any admissions. Meteorologic factors for the days with admissions and 1-3 days before hospitalization were compared with those of the days of no admissions. Statistical analysis was done with the Mann-Whitney U-test. RESULTS: On the days with admissions and 1 day before hospitalizations, barometric pressure was higher and relative humidity lower than on days with no admissions. The diurnal difference between maximum and minimum temperature for days 1 day before days with admissions was larger than that for 1 day before days with no admissions. CONCLUSIONS: It is thought that change in barometric pressure, relative humidity and temperature had some influence on the worsening of asthmatic symptoms.

Asthma↗
PubMed1999

Three point mutations of human butyrylcholinesterase in a Japanese family and the alterations of three-dimensional structure.

Three different mutations at codons 330 (TTA to ATA), 365 (GGA to AGA) and 515 (CGT to TGT) of human butyrylcholinesterase (hBChE) were identified in a Japanese family. We correlated alterations in in the patient's hBChE activity with possible structural alterations in the three-dimensional structure of hBChE caused by the point mutations. This study was performed using the published computer-generated three-dimensional structure of hBChE based on the structure of acetylcholinesterase. The amino acid substitution at L330I was adjacent to hydrophobic residues that form the channel domain of the active center. This side chain faced the side opposite the active center. The amino acid substitution at G365R was located at the position most remote from the active center, and this substitution site was exposed to the surface of the BChE protein. Alpha-helical structure was present to the active center, and the guanidyl residue of native Arg 515 was hydrogen-bonded to the carboxyl group of Asp 395 in the alpha-helix. These point mutations may cause steric effects on the present patient's hBChE activity. This is the first report of three-dimensional structural analysis performed on the L330I, G365R, and R515C mutations of hBChE.

Adult↗
PubMed1999

[The control survey in CD marker analysis of leukemic cells].

Analysis of cell surface antigens is thought to be more objective compared to classification by the morphology. However, it has been indicated that the evaluated data are different each other between institutes. Therefore, we performed a control survey of CD marker analysis in leukemia cells using flow cytometry in six commercial laboratories. The expression of CD2, 4, 5, 7, 8, 10, 13, 14, 19, 20, 33, 34, 38, and 71, HLA-DR in tumor cells from megakaryoblastic leukemia, lymphoblastic crisis of CML, and ALL patients, were examined. There were large differences in the results of CD marker analysis among the six commercial laboratories. One possible reason for this result is the differences in gating condition and monoclonal antibodies used in each laboratory. However, there were the differences in the results even when the same gating condition and antibodies were used. The reasons for the difference in transport or treatment conditions for samples remain a matter of considerable controversy. In the present condition, it was suggested that the exchange of information about the origin of tumor cells between the physician in charge and examination experts is thought to be the best way to analyze proper cell surface antigen expression. Further, no national survey has been carried out, but the establishment of a standard assay is preferred to obtain proper data for the patients and medical parties concerned.

Adolescent↗
PubMed1999

Detection of human serum tumor necrosis factor-alpha in healthy donors, using a highly sensitive immuno-PCR assay.

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha) is an important mediator of inflammatory and autoimmune diseases. Analysis of its pathophysiologic roles has been difficult because low concentrations of TNFalpha, including those in healthy controls, cannot be measured by existing methods. METHODS: We developed a sensitive immuno-PCR assay for the detection of TNFalpha in human serum. The DNA label was generated by PCR amplification using biotinylated primer and was bound with streptavidin to the biotinylated third antibody. TNFalpha sandwiched by antibodies was detected by amplification of the DNA label using PCR. RESULTS: The limit of detection of the assay was 0. 001 ng/L, an approximately 5 x 10(4)-fold improvement compared with a conventional ELISA. The mean serum TNFalpha concentration (+/- SD) in healthy donors was 0.021 +/- 0.044 ng/L in men (n = 29) and 0.033 +/- 0.065 ng/L in women (n = 25). CONCLUSION: This method may be useful for analyzing the significance of TNFalpha concentration in various diseases.

Adult↗