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Makoto Takahashi

Publications and source records attributed to Makoto Takahashi.

At least 19 recordsLinked to original sources
PubMed2007

Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/tandem mass spectrometry.

Two fast and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based bioanalytical assays were developed and validated to quantify the active and three inactive metabolites of prasugrel. Prasugrel is a novel thienopyridine prodrug that is metabolized to the pharmacologically active metabolite in addition to three inactive metabolites, which directly relate to the formation and elimination of the active metabolite. After extraction and separation, the analytes were detected and quantified using a triple quadrupole mass spectrometer using positive electrospray ionization. The validated concentration range for the inactive metabolites assay was from 1 to 500 ng/mL for each of the three analytes. Additionally, a 5x dilution factor was validated. The interday accuracy ranged from -10.5% to 12.5% and the precision ranged from 2.4% to 6.6% for all three analytes. All results showed accuracy and precision within +/-20% at the lower limit of quantification and +/-15% at other levels. The validated concentration range for the active metabolite assay was from 0.5 to 250 ng/mL. Additionally, a 10x dilution factor was validated. The interbatch accuracy ranged from -7.00% to 5.98%, while the precision ranged from 0.98% to 3.39%. Derivatization of the active metabolite in blood with 2-bromo-3'-methoxyacetophenone immediately after collection was essential to ensure the stability of the metabolite during sample processing and storage. These methods have been applied to determine the concentrations of the active and inactive metabolites of prasugrel in human plasma.

Chromatography, High Pressure Liquid↗
PubMed2006

Mechanism for covalent binding of rofecoxib to elastin of rat aorta.

We have previously reported that oral administration of [(14)C]rofecoxib to rats resulted in the long retention of radioactivity by the aorta as a consequence of covalent binding to elastin. Treatment of rats with alpha-phenyl-alpha-propylbenzeneacetic acid 2-[diethylamino]-ethyl ester hydrochloride (SKF-525A), a cytochrome P450 inhibitor, significantly decreased the systemic exposure of 5-hydroxyrofecoxib, one of the main metabolites of rofecoxib, whereas there was no statistically significant change in the retention of radioactivity from [(14)C]rofecoxib in the aorta. On the other hand, the aortic retention of radioactivity closely correlated to the systemic exposure of unchanged rofecoxib in the dose range between 2 and 10 mg/kg. A covalent binding study of [(14)C]rofecoxib in vitro using rat aorta homogenate in the presence of d-penicillamine, hydralazine, beta-aminopropionitrile, and sodium borohydride suggested that the aldehyde group of allysine in elastin was relevant to the covalent binding. In a model reaction using benzaldehyde, rofecoxib but not 5-hydroxyrofecoxib reacted with the aldehyde group of benzaldehyde in a manner of condensation reaction under a physiological pH condition. A histopathological examination using an electron microscope demonstrated that multiple oral administration of rofecoxib to rats caused marked degradation of the elastic fiber system of the aorta. These results suggested that rofecoxib as such is reactive in vivo, undergoing a condensation reaction with allysine, thereby preventing the formation of cross-linkages in elastin, i.e., desmosine and isodesmosine, and causing the degradation of the elastic fibers.

Animals↗
PubMed2006

Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment.

Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up-regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up-regulation in the limbic system with a biological link to sensorimotor gating deficits.

Aging↗
PubMed2006

The neural basis of the hemodynamic response nonlinearity in human primary visual cortex: Implications for neurovascular coupling mechanism.

It has been well recognized that the nonlinear hemodynamic responses of the blood oxygenation level-dependent (BOLD) functional MRI (fMRI) are important and ubiquitous in a series of experimental paradigms, especially for the event-related fMRI. Although this phenomenon has been intensively studied and it has been found that the post-capillary venous expansion is an intrinsically nonlinear mechanical process, the existence of an additional neural basis for the nonlinearity has not been clearly shown. In this paper, we assessed the correlation between the electric and vascular indices by performing simultaneous electroencephalography (EEG) and fMRI recordings in humans during a series of visual stimulation (i.e., radial checkerboard). With changes of the visual stimulation frequencies (from 0.5 to 16 Hz) and contrasts (from 1% to 100%), both the event related potentials (ERPs) and hemodynamic responses show nonlinear behaviors. In particular, the mean power of the brain electric sources and the neuronal efficacies (as originally defined in the hemodynamics model [Friston et al. Neuroimage, 12, 466-477, 2000], here represent the vascular inputs) in primary visual cortex consistently show a linear correlation for all subjects. This indicates that the hemodynamic response nonlinearity found in this paper primarily reflects the nonlinearity of underlying neural activity. Most importantly, this finding underpins a nonlinear neurovascular coupling. Specifically, it is shown that the transferring function of the neurovascular coupling is likely a power transducer, which integrates the fast dynamics of neural activity into the vascular input of slow hemodynamics.

Adult↗
PubMed2006

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

Adolescent↗
PubMed2006

Excitability changes in human hand motor area induced by voluntary teeth clenching are dependent on muscle properties.

To investigate whether the early effects of voluntary teeth clenching (VTC) among the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor pollicis brevis (APB) muscles are differently modulated depending on their muscle properties, we examined the responses of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation with selected current directions and by brainstem magnetic stimulation (BMS). Although MEP responses with anterior-medially current direction (preferentially elicited I1-waves) were facilitated in all three muscles, those responses with posterior-laterally current direction (preferentially elicited I3-waves) were different among FDI, ADM, and APB muscles. That is, MEP responses in FDI and APB muscles were significantly reduced, whereas those responses in ADM muscle were not significantly reduced. Further, inhibitory effects of VTC in FDI muscle were more potent than those in ADM or APB muscles. On the other hand, the responses to BMS were unchanged by VTC in all three muscles, suggesting that the modulations of MEP were attributed to the cortical origin. On the basis of our previous findings that the inhibitory connections in FDI muscle are more potent than those in ADM muscle (Takahashi et al. in Clin Neurophysiol 116:2757-2764, 2005), the cortical effects of VTC among three hand muscles are differently modulated, depending on muscle properties, presumably the extents of inhibitory connections to corticospinal tract neurons. Considering that the functional capacity in FDI muscle is higher than that in ADM or APB muscles, the cortical inhibitory effect of VTC might contribute to the sophisticated regulation of the motor outputs even during VTC.

Adult↗
PubMed2006

An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis.

Evidence suggests that CD4+CD25+ regulatory T cells play a crucial role in the suppression of intestinal inflammation. However, their role in the suppression of inflammatory bowel disease has not yet been addressed. We examined the proportion of regulatory T cells in inflammatory bowel disease. First, we isolated CD4+CD45RO+CD25+ T cells from the peripheral blood of healthy persons and showed that these cells suppressed T cell proliferation profoundly and expressed FoxP3 abundantly, revealing that they are regulatory cells. Then the proportion of CD45RO+CD25+ in peripheral blood CD4+ T cells was analyzed in patients and healthy controls by flow cytometry. CD4+CD45RO+CD25+ T cell frequency was significantly lower in active ulcerative colitis than in the control and inactive ulcerative colitis. CD4+CD45RO+CD25+ T cell frequency was inversely correlated with the clinical and endoscopic severity of ulcerative colitis. These results suggest that a deficiency of regulatory T cells is associated with the progression of ulcerative colitis.

Adolescent↗
PubMed2006

Motor strategies and excitability changes of human hand motor area are dependent on different voluntary drives.

The present study examined whether there were different voluntary drives between intended and non-intended muscle contractions. In experiment 1, during intended and non-intended muscle contractions, electromyograms (EMGs) were recorded from the first dorsal interosseous (FDI) and extensor carpi radialis (ECR) muscles when force levels were varied from 10% to 50% maximal voluntary contraction (MVC) in 10% MVC steps. In experiment 2, using transcranial magnetic stimulation, motor-evoked potentials (MEPs) were recorded from the FDI muscle when EMGs were varied from 10% to 40% EMGmax (EMG activities during MVC) in 10% EMGmax steps during intended and non-intended muscle contractions. In experiment 3, at 10% MVC force level MEPs were recorded before and after practice. The results showed that, in the FDI muscle, EMGs during intended muscle contractions were larger than those during non-intended ones at higher force levels (30-50% MVC). In the ECR muscle, reverse results were observed. At comparable EMG levels of the FDI muscle MEPs were the same during intended and non-intended muscle contractions. After practice, MEPs during intended muscle contraction became larger than those during non-intended at 10% MVC force level, while EMGs were the same between two muscle contractions. It is concluded that motor strategies and excitability changes of hand motor area are different during intended and non-intended muscle contractions, and these differences are due to the different voluntary drives of intended and non-intended. The present findings may contribute to the understanding of rehabilitation for patients suffering from damages of the central motor system.

Adult↗
PubMed2006

Adsorption characteristics of a nanodiamond for oxoacid anions and their application to the selective preconcentration of tungstate in water samples.

A nanodiamond with a mean particle size of 4 nm, which was prepared by the detonation of a nanodiamond, has been characterized and used as a collector for tungstate in water samples. An aqueous solution of nanodiamond was found to be stable over the pH range from 3 to 10. Coagulation of the nanodiamond could be brought about by adding an electrolyte solution. The adsorption characteristics of nanodiamond have been elucidated to be attributable to amino groups on its surface by the elemental-analysis data and the zeta potential measured in weak acid media. The unique adsorption properties of the nanodiamond for oxoacid anions were applied to a selective preconcentration method for tungstate in water samples. An appropriate amount of nanodiamond was added to a sample solution at pH 5 and a calcium chloride solution was added to aggregate nanodiamond. The sample solution was then allowed to stand for 2 h and centrifuged. The nanodiamond was transferred onto a membrane filter, washed with a diluted calcium chloride solution and treated in advance of an ICP-AES measurement by either of the following procedures: (a) redispersion of the nanodiamond into dilute nitric acid with an ultrasonic washer and (b) ashing of the membrane filter and the coagulated nanodiamond at 700 degrees C, followed by a treatment of the ash with hydrochloric and tartaric acids. The average recovery of tungstate from 100-ml artificial river-water was found to be 99% at the 0.25 ppm level with an RSD of 2.2% (n = 3). The concentration factor at present is 10.

Journal Article↗
PubMed2005

Functional demanded excitability changes of human hand motor area.

The present study was performed to examine if there are functional differences between the first dorsal interosseous (FDI) and the abductor digit minimi (ADM) muscles during different muscle contractions, namely dynamic and static contractions of the index and little finger abductions. It was also examined whether these functional differences occur at the cortical level. The motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) and force curves, during the muscle contractions, were simultaneously recorded. Rest motor thresholds (RMTs) and active motor thresholds (AMTs), during dynamic and static contractions, were determined in the two muscles. In all trials, the background EMGs (B.EMGs) were kept at the same level in each muscle. Results showed that the target matching errors of dynamic contractions were statistically smaller in the FDI muscle than those in the ADM. In the FDI muscle, the AMT during dynamic contractions was significantly lower than during static ones and the MEPs elicited by TMS were larger during dynamic contractions than those during static ones. However, such results were not found in the ADM muscle. In order to investigate whether the differences were caused by the excitability changes that occurred in the cortical level, the responses elicited by subcortical stimulations were recorded using the same procedures as the experiment of TMS. Responses to subcortical stimulations during dynamic contractions were similar to those during static ones in either muscle. It is concluded that there are differences in the task-dependent MEP facilitations between the FDI and ADM muscles. And the differences are due to the functional demanded excitability changes accompanied by the cortical activation.

Adult↗
PubMed2005

Differential modulations of intracortical neural circuits between two intrinsic hand muscles.

OBJECTIVE: To investigate whether the intracortical inhibitory (ICI) and facilitatory (ICF) circuits in the primary motor cortex between the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are modulated differently. METHODS: We conducted paired-pulse transcranial magnetic stimulation in combination with different current directions (anterior-medially: AM, and posterior-laterally: PL) under relaxed and active muscle conditions with interstimulus intervals (ISIs) between 2 and 16 ms. RESULTS: In both muscle conditions, the conditioned motor-evoked potential (MEP) responses obtained with the AM current direction (preferentially eliciting early I-waves) were similar between the two muscles at all ISIs, but the MEP responses obtained with the PL current direction (preferentially eliciting late I-waves) were different between FDI and ADM muscles, in that the conditioned MEP responses in FDI muscle were inhibited at all ISIs under both muscle conditions, whereas those in ADM muscle were suppressed at only short ISIs (2-4 ms). CONCLUSIONS: These results indicate that the inhibitory connections operating for the corticospinal tract neurons in FDI muscle are more potent, and, conversely, that those in ADM muscle are weaker. SIGNIFICANCE: The different modulations of ICI circuits between FDI and ADM muscles is an important neural mechanism which may contribute to different functional demands (finger dexterity).

Adult↗
PubMed2005

Separation of copolymers using high-performance liquid chromatography with polymeric stationary phase and liquefied carbon dioxide as adsorption promoting solvent.

Chromatographic separation of copolymers depending on the chemical composition was studied by a solvent gradient method using liquefied carbon dioxide (CO2) as an adsorption promoting solvent. As the high polar stationary phase, non-bonded silica gel, crosslinked acrylamide (AA) gel and crosslinked acrylonitrile (AN) gel were utilized. All columns showed the typical normal phase type of adsorption. Polymeric stationary phases showed the higher sample recovery for styrene-methyl methacrylate (St-MMAs) copolymers, indicating suitability for quantitative analyses. The separations of butyl methacrylate (BMA)-methyl methacrylate, and 2,2,3,3,4,4,4-heptafluorobutyl methacrylate (FBMA)-methy methacrylate copolymers were also carried out, and the latter copolymers were separated based on the CO2-philicity with acrylonitrile column.

Adsorption↗
PubMed2005

Physical practice induces excitability changes in human hand motor area during motor imagery.

The present study was undertaken to investigate the effects of physical practice on excitability changes in human primary motor cortex (M1) during motor imagery (MI). Using different intensities of transcranial magnetic stimulation (TMS), we examined changes in the motor evoked potential (MEP) of the first dorsal interosseous (FDI) muscle with and without MI, and before and after physical practice. On comparing results for MEPs recorded before and after physical practice, the difference between the MEP amplitudes observed at rest and during MI only increased at higher TMS intensities. This finding indicates a physical practice-dependent increase of the higher threshold recruitment of corticospinal tract neurons (CTNs), consistent with synchronization for efficient movement, and provides evidence that neural mechanisms of MI depend not only on the type of movement but also on the extent of the motor adaptation (the physical practice). These present findings also show the benefit of MI and highlight beneficial neural mechanisms related to the activation of M1 during MI. In other words, MI may reflect functional changes of M1 that are similar to the changes observed after physical practice.

Adult↗
PubMed2005

Remote effects of voluntary teeth clenching on excitability changes of the human hand motor area.

The aim of the present study was to investigate effects of voluntary teeth clenching (VTC) on motor evoked potentials (MEPs) from the first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) by different oriented currents (anterior-medially (AM), posterior-laterally (PL)) of the human motor cortex. In active FDI, VTC enhanced MEP responses induced by AM directed current but reduced these responses induced by PL. In relaxed FDI, VTC enhanced MEP responses by AM but had no significant effects on those by PL. Thus, the results suggest that any components produced by AM directed current were enhanced, whereas those by PL directed currents were not affected or reduced. The present evidence indicates that I-waves recorded at the same latency were not completely the same between those produced by AM and PL directed currents. Because VTC had no influence on responses to brainstem electrical stimulation (BES) or F-waves just after the onset of teeth clenching [T. Furubayashi, K. Sugawara, T. Kasai, A. Hayashi, R. Hanajima, Y. Shiio, N.K. Iwara, Y. Ugawa, Remote effects of self-paced teeth clenching on the excitability of hand motor area, Exp. Brain Res., 148 (2003) 261-265], these modulatory effects on MEPs to both AM and PL directed currents must be due to changes of the motor cortical excitability. Thus, we conclude that VTC affects the motor cortical circuits activated by PL and AM directed currents differentially; it facilitates the one and inhibits the other. This is the first demonstration of opposite effects of the same maneuver on MEP responses elicited by AM and PL directed currents.

Adult↗
PubMed2005

Cortical activation during reading of ancient versus modern Japanese texts: fMRI study.

The purpose of this study was to investigate human brain activity during the reading of ancient Japanese texts using functional magnetic resonance imaging. Thirty right-handed normal Japanese subjects performed two reading tasks: covert reading of (1) ancient and (2) modern Japanese text. Common areas are activated during both tasks. Activity in the left inferior frontal cortices increased during the reading of ancient Japanese text compared with the reading of modern Japanese text, whereas occipital activity increased during the reading of modern Japanese text. Our results indicate that ancient Japanese language may be processed as a foreign language.

Adolescent↗
PubMed2005

T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis.

BACKGROUND: WSX-1, a component of the interleukin (IL)-27 receptor, is a novel class I cytokine receptor with homology to the IL-12 receptor beta2 chain. Initially, WSX-1 signaling was reported to play an important role in the promotion of T helper-1 responses, but recent reports have revealed an anti-inflammatory property in WSX-1 signaling. In the present study, we investigated the role of IL-27/WSX-1 signaling in a murine colitis model, dextran sulfate sodium (DSS) colitis, by using WSX-1 knockout (KO) mice. METHODS: First, we observed whether WSX-1 KO mice developed colitis spontaneously. Second, we induced DSS colitis in WSX-1 KO and wild-type (WT) mice. RESULTS: WSX-1 KO mice were observed not to develop colitis spontaneously. The severity of DSS colitis was decreased in WSX-1 KO mice in comparison with WT mice in association with a reduced production of interferon-gamma, IL-6, and tumor necrosis factor-alpha by lamina propria mononuclear cells from WSX-1 KO mice and the absence of T-bet expression in the colon from WSX-1 KO mice. CONCLUSIONS: This study revealed the inflammatory property of IL-27/WSX-1 signaling in intestinal inflammation. As a result, IL-27/WSX-1 signal pathway may thus be a promising candidate for the therapeutic intervention of human inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.

Animals↗
PubMed2005

Sinus floor elevation applied tissue-engineered bone. Comparative study between mesenchymal stem cells/platelet-rich plasma (PRP) and autogenous bone with PRP complexes in rabbits.

In the present study, we compared bone regeneration ability in sinus floor elevation between a tissue engineering method using mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP), and a promising new method using particulate cancellous bone and marrow (PCBM) and PRP. Bilateral sinus floor elevation procedures were performed in 18 adult Japanese white rabbits. MSCs/PRP or PCBM/PRP complexes were grafted to each maxillary sinus in the same rabbits. The MSCs were isolated from rabbit iliac crest marrow, and PRP was obtained from peripheral blood. PCBM were collected from the rabbit iliac crest and mixed with PRP. The animals were sacrificed at 2, 4, and 8 weeks after transplantation, and the bone formation ability of each implant was evaluated histologically and histometrically. According to the histological observations, both sites (MSCs/PRP and PCBM/PRP) showed well newly formed bone and neovascularization at 2 and 4 weeks. However, at 8 weeks, the lamellar bone was observed to be occupied by fatty marrow in large areas in both sites. There was no significant difference in bone volume or augmented height between MSCs/PRP and PCBM/PRP groups each week, but there were significant differences in bone volume and augmented height between 2 and 8 weeks in PCBM/PRP or MSCs/PRP groups and in bone volume between 4 and 8 weeks in the PCBM/PRP group (P<0.05). These results suggest that the MSCs/PRP complex may well be used for bone regeneration in sinus floor elevation, compared with the PCBM/PRP complex.

Animals↗