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A Takeuchi

Publications and source records attributed to A Takeuchi.

At least 19 recordsLinked to original sources
PubMed2006

Modelling Cl- homeostasis and volume regulation of the cardiac cell.

We aim at introducing a Cl- homeostasis to the cardiac ventricular cell model (Kyoto model), which includes the sarcomere shortening and the mitochondria oxidative phosphorylation. First, we examined mechanisms underlying the cell volume regulation in a simple model consisting of Na+/K+ pump, Na+-K+-2Cl- cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance regulator, volume-regulated Cl- channel and background Na+, K+ and Cl- currents. The high intracellular Cl- concentration of approximately 30 mM was achieved by the balance between the secondary active transport via NKCC1 and passive currents. Simulating responses to Na+/K+ pump inhibition revealed the essential role of Na+/K+ pump in maintaining the cellular osmolarity through creating the negative membrane potential, which extrudes Cl- from a cell, confirming the previous model study in the skeletal muscle. In addition, this model well reproduced the experimental data such as the responses to hypotonic shock in the presence or absence of beta-adrenergic stimulation. Finally, the volume regulation via Cl- homeostasis was successfully incorporated to the Kyoto model. The steady state was well established in the comprehensive cell model in respect to both the intracellular ion concentrations and the shape of the action potential, which are all in the physiological range. The source code of the model, which can reproduce every result, is available from http://www.sim-bio.org/.

Animals↗
PubMed2004

Nature of the well screened state in hard X-ray Mn 2p core-level photoemission measurements of La1-xSrxMnO3 films.

Using hard x-ray (HX; hnu=5.95 keV) synchrotron photoemission spectroscopy (PES), we study the intrinsic electronic structure of La(1-x)Sr(x)MnO(3) (LSMO) thin films. Comparison of Mn 2p core-levels with soft x-ray (SX; hnu approximately 1000 eV) PES shows a clear additional well-screened feature only in HX PES. Takeoff-angle dependent data indicate its bulk (> or =20 A) character. The doping and temperature dependence track the ferromagnetism and metallicity of the LSMO series. Cluster model calculations including charge transfer from doping-induced states show good agreement, confirming this picture of bulk properties reflected in Mn 2p core-levels using HX PES.

Journal Article↗
PubMed2003

Association of transporter associated with antigen processing genes with Behçet's disease in Japanese.

Contribution of transporter associated with antigen processing (TAP) genes to the pathogenesis of Behçet's disease (BD) was studied. Restriction fragment length polymorphic analysis of TAP genes was carried out in 46 Japanese patients with BD and 95 healthy subjects. There were no significant differences in allele frequencies of TAP1 and TAP2 genes between whole patients with BD and control population. No significant differences in the frequencies of TAP alleles were observed, when patients of BD with complete type or incomplete type were compared with control population, respectively. An allele frequency of TAP2C was, however, slightly but significantly high in patients with BD who had symptom of erythema nodosum (24.1%) as compared to the control group (11.6%). [p < .05, RR = 2.4]. The allele frequency of TAP2C was slightly high in HLA*B5101 positive patients with BD (28.6%) as compared to HLA*B5101 negative patients (10.9%), but the difference did not reach statistical significance. The absence of genotype TAP2B/C was observed in whole patients group, though it was present in control subjects (14.7%). [p = 0.003, RR = 0.06]. A genotype frequency of TAP2C/H was high in patients with BD who had symptom of skin lesions (7.5%) as compared to the control group (0.0%). [p = 0.03, RR = 15.4]. These results suggest the possibility that TAP molecule play some part in formation of skin lesion, such as erythema nodosum in BD in Japanese.

ATP-Binding Cassette Transporters↗
PubMed2002

Methyl isobutyl ketone and methyl ethyl ketone in urine as biological markers of occupational exposure to these solvents at low levels.

OBJECTIVE: To examine whether unmetabolized methyl isobutyl ketone in urine is a useful marker of low-level occupational exposure to this ketone solvent, as is the case for methyl ethyl ketone. METHODS: The study was conducted in the second half of a working week. In total, 27 furniture-making workers (19 men and eight women) and 11 non-exposed controls (six men and five women) volunteered to participate in the study. Time-weighted average (TWA; 8-h) concentration of vapors of several solvents in air, including methyl isobutyl ketone (MIBK-A) and methyl ethyl ketone (MEK-A) was monitored by diffusive sampling. Urine samples collected at the end of the shift were subjected to head-space gas chromatography (GC) analysis for the unmetabolized solvents (i.e., MIBK-U and MEK-U). The relationship between the concentration of the solvent vapor and the corresponding solvent level in urine was examined by simple as well as multiple regression analysis. RESULTS: The exposures to MIBK and MEK were well below the current occupational exposure limit levels, but the maximum levels of exposure to toluene and ethylbenzene were around the corresponding exposure limit. The correlation of the TWA concentration of the solvent in air with the concentration of the corresponding solvent in the end-of-shift urine sample was significant both for MIBK and for MEK, and the correlation coefficient was larger for MIBK than for MEK. The slope in the exposure-excretion regression line was almost twice as steep for MEK than for MIBK, possibly due to the difference in water solubility. Approximately 0.12% of MIBK absorbed in the lungs will be excreted into urine, whereas the yield for MEK was somewhat higher (0.19%). CONCLUSION: MIBK in urine is a good marker of exposure to MIBK, as in the case of MEK in urine for MEK exposure.

Adult↗
PubMed2002

Anti-angiogenic action of hyperthermia by suppressing gene expression and production of tumour-derived vascular endothelial growth factor in vivo and in vitro.

Vascular endothelial growth factor is an important angiogenic factor for tumour progression because it increases endothelial-cell proliferation and remodels extracellular matrix in blood vessels. We demonstrated that hyperthermia at 42 degrees C, termed heat shock, suppressed the gene expression and production of vascular endothelial growth factor in human fibrosarcoma HT-1080 cells and inhibited its in vitro angiogenic action on human umbilical vein endothelial cells. The gene expression of alternative splicing variants for vascular endothelial growth factor, VEGF121, VEGF165 and VEGF189, was constitutively detected in HT-1080 cells, but the VEGF189 transcript was less abundant than VEGF121 and VEGF165. When HT-1080 cells were treated with heat shock at 42 degrees C for 4 h and then maintained at 37 degrees C for another 24 h, the gene expression of all vascular endothelial growth factor variants was suppressed. In addition, HT-1080 cells were found to produce abundant VEGF165, but much less VEGF121, both of which were inhibited by heat shock. Furthermore, the level of vascular endothelial growth factor in sera from six cancer patients was significantly diminished 2-3 weeks after completion of whole-body hyperthermia at 42 degrees C (49.9+/-36.5 pg x ml(-1), P<0.01) as compared with that prior to the treatment (177.0+/-77.5 pg x ml(-1)). On the other hand, HT-1080 cell-conditioned medium showed vascular endothelial growth factor-dependent cell proliferative activity and the augmentation of pro-matrix metalloproteinase-1 production in human umbilical vein endothelial cells. The augmentation of endothelial-cell proliferation and pro-matrix metalloproteinase-1 production was poor when human umbilical vein endothelial cells were treated with conditioned medium from heat-shocked HT-1080 cells. These results suggest that hyperthermia acts as an anti-angiogenic strategy by suppressing the expression of tumour-derived vascular endothelial growth factor production and thereby inhibiting endothelial-cell proliferation and extracellular matrix remodelling in blood vessels.

Cell Division↗
PubMed2002

Toluene, xylenes and xylene isomers in urine as biological indicators of low-level exposure to each solvent; a comparative study.

OBJECTIVE: To examine if xylenes and xylene isomers in end-of-shift urine are good biological indicators of low-level exposure to each solvent, similarly to toluene in urine. METHODS: The study was conducted in the latter half of a working week. Furniture makers, 86 subjects in total (76 men and ten women), participated in the study in combination with 11 non-exposed subjects. Time-weighted average (8-h TWA) exposures to mixtures of toluene (TOL-A), xylenes (XYLs-A), ethylbenzene (EB-A), acetone (ACE-A) etc. were monitored with diffusive samplers for lipophilic and hydrophilic solvents, respectively. Urine samples (i.e., TOL-U, XYLs-U, EB-U, ACE-U, etc.) were collected at the end of the shift and subjected to head-space gas chromatography analysis for each solvent. The exposure-excretion relationship was examined by simple as well as multiple regression analysis. RESULTS: The exposures to TOL and XYLs were around or below current occupational exposure limit levels. The exposures to other solvents [i.e., ACE, EB, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), etc.] were at substantially lower levels. The correlation of the TWA solvent exposure concentration with the concentration of the corresponding solvent in the end-of-shift urine sample was close for TOL, and also almost equally close in the case of XYLs and each of the three XYL isomers. Whereas the slope of the regression line for XYLs was significantly less steep than that for TOL when compared on an equi-molar basis, there was no difference among the three XYL isomers. No confounding effects of age, sex and co-exposure to other solvents were detected. The observation confirms previous reports that TOL-U is a good marker of TOL vapor exposure, indicates that XYL-U is also a reliable marker of exposure to vapors of XYLs or any of the three XYL isomers, and suggests that estimation of exposure to vapors of XYLs (i.e., three isomers in combination) is possible by the determination of one of the XYL isomers in urine, once the proportion of the isomers in air is known. Possible association of water solubility with solvent levels in urine is discussed. CONCLUSIONS: Biological monitoring of exposure by means of analysis of end-of-shift urine for mother solvent is possible, not only in the case of TOL as previously reported, but also in cases of XYLs, either for three isomers in combination or separately.

Adult↗
PubMed2002

Development of a multilayer Fresnel zone plate for high-energy synchrotron radiation X-rays by DC sputtering deposition.

Hard X-ray microscopy with high spatial resolution ( or=20 keV) because a large thickness (aspect ratio) can be available. Various types of multilayer FZPs have been fabricated by DC sputtering deposition. Their focusing characteristics have been evaluated at the high-brilliance undulator beamline BL47XU of SPring-8. An optical system using a Cu/Al multilayer FZP (with an outermost zone width of 0.25 microm) as the focusing optics fabricated by the optimum deposition condition with precise film (zone) thickness control has attained an almost diffraction-limited microbeam of 0.3-0.35 microm at 8.9 keV. A line-and-space resolution test pattern has been observed: fine structures up to 0.2 microm were clearly observed in the measured image. This FZP has been working since 1995, keeping good focusing characteristics. It can be said from these results that a spatial resolution better than 0.1 microm in the high-energy X-ray region is in prospect by the development of a multilayer FZP with a narrower outermost zone width in the near future.

Journal Article↗
PubMed2002

Hard X-ray microbeam experiments with a sputtered-sliced Fresnel zone plate and its applications.

Hard X-ray microbeam experiments with sputtered-sliced Fresnel zone plates have been performed. Zone plates with an outermost zone width of 0.25 microm (#FZP1) and 0.1 microm (#FZP2) were fabricated and evaluated. In a scanning X-ray microscopy experiment, a line-and-space pattern with structure as fine as 0.1 microm was resolved using #FZP2 at an X-ray wavelength of 1 A. As an application of the microbeam technique, a two-dimensional distribution of constituent elements in forensic samples has been obtained (e.g. section view of human and elephant hairs) using fluorescent scanning microscopy.

Animals↗
PubMed2002

Zernike-type X-ray imaging microscopy at 25 keV with Fresnel zone plate optics.

A Zernike-type imaging microscope using a sputtered-sliced Fresnel zone plate (SS-FZP) has been developed and tested at an X-ray energy of 25 keV. The SS-FZP was used as an objective. A copper (Cu) phase plate was placed at the back focal plane of the SS-FZP in order to produce phase contrast. The performance of the Zernike-type imaging microscope was tested with a gold (Au) mesh and a resolution test pattern at undulator beamline 47 of SPring-8. The Au mesh and the resolution test pattern could be imaged in transmission with a magnification of x10.2. Owing to the Cu phase plate, different image contrast was observed compared with the bright-field image contrast. Tantalum microstructures down to 0.5 microm line-and-space have been observed on spatial resolution test patterns.

Journal Article↗
PubMed2001

Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules.

To maintain various T cell responses and immune equilibrium, activation signals triggered by T cell antigen receptor (TCR) must be regulated by inhibitory signals. Gab2, an adaptor protein of the insulin receptor substrate-1 family, has been shown to be involved in the downstream signaling from cytokine receptors. We investigated the functional role of Gab2 in TCR-mediated signal transduction. Gab2 was phosphorylated by ZAP-70 and co-precipitated with phosphoproteins, such as ZAP-70, LAT, and CD3zeta, upon TCR stimulation. Overexpression of Gab2 in Jurkat cells or antigen-specific T cell hybridomas resulted in the inhibition of NF-AT activation, interleukin-2 production, and tyrosine phosphorylation. The structure-function relationship of Gab2 was analyzed by mutants of Gab2. The Gab2 mutants lacking SHP-2-binding sites mostly abrogated the inhibitory activity of Gab2, but its inhibitory function was restored by fusing to active SHP-2 as a chimeric protein. A mutant with defective phosphatidylinositol 3-kinase binding capacity also impaired the inhibitory activity, and the pleckstrin homology domain-deletion mutant revealed a crucial function of the pleckstrin homology domain for localization to the plasma membrane. These results suggest that Gab2 is a substrate of ZAP-70 and functions as a switch molecule toward inhibition of TCR signal transduction by mediating the recruitment of inhibitory molecules to the TCR signaling complex.

Adaptor Proteins, Signal Transducing↗
PubMed2001

E2A and HEB activate the pre-TCR alpha promoter during immature T cell development.

The pre-TCRalpha (pTalpha) is exclusively expressed in immature thymocytes and constitutes the pre-TCR complex with TCRbeta, which regulates early T cell differentiation. Despite the recent identification of the pTalpha enhancer, the contribution of the promoter region, the direct DNA-protein interaction, and the regulation of such interaction along with T cell development have not been investigated. We analyzed the pTalpha promoter region and identified the critical elements for transcription of the pTalpha gene. The pTalpha promoter was found to contain two consecutive E-box elements that are critical for pTalpha transcription. The E-box elements in the promoter region formed the specific DNA-protein complex that was exclusively observed in immature thymocytes, not in mature thymocytes and T cells. The E proteins in this complex were identified as E2A and HeLa E-box binding protein (HEB), and overexpression of E2A and HEB resulted in activation of the pTalpha promoter. The binding complex in the consecutive E-boxes in the pTalpha promoter changed along with T cell development, as a distinct DNA-binding complex was observed in mature T cells. Comparing the E-box regions in the enhancer and the promoter, those in the promoter appear to make a greater contribution to pTalpha gene transcription.

Animals↗
PubMed2001

Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury.

In a previous study, we have demonstrated that damaged neurons within a boundary area around necrosis fall into delayed neuronal death owing to the cytotoxic effect of microglial nitric oxide (NO), and these neurons are finally eliminated by activated microglia. In this process, microglia are activated to release NO, increase in number, and accumulate toward the damaged area. In this study, we investigated the expression of macrophage colony-stimulating factor (M-CSF, also called colony stimulating factor-1; CSF-1) and other cytokines, which are reported to relate to activation, proliferation, or migration of microglia. The mRNA of M-CSF arose biphasically from 30 min to 1 hr and from 6 to 72 hr after the injury, as demonstrated by semiquantitative RT-PCR. However, another cytokine of granulocyte-macrophage CSF (GM-CSF) or interleukin-3 (IL-3), which causes proliferation of microglia in vitro, was not detected. From immunohistochemical studies, positive staining of M-CSF was observed mainly in neuron-specific enolase (NSE)-positive cells from 1 to 12 hr after the injury, and after that M-CSF became positive in Griffonia simplicifolia isolectin-B4 (GSA-I-B4)-positive cells from 24 to 72 hr in the boundary area around necrosis. These results suggest that neurons around the damaged area express M-CSF in the early phase after injury, which may initially activate microglia, and these activated microglia also express M-CSF later, causing further proliferation or migration of microglia themselves to eliminate damaged neurons or necrotic brain tissue.

Animals↗
PubMed2001

Urinary bromide levels probably dependent to intake of foods such as sea algae.

The purpose of the present study is to examine if the bromide (Br) level in urine (Br-U) varies substantially among adult general populations of either sex or of different dietary habits. For this purpose, morning spot urine samples (about 50 per group) were collected from six groups of people, i.e., one group each of men and women in a city in Japan (thus two groups in Japan) and one group each of women in two urban and two rural areas in central and northeast China (four groups in China). The samples were analyzed for Br by ECD-gas chromatography after derivatization to methyl bromide. Br-U essentially followed a normal distribution. Whereas there was only a marginal difference in Br-U between men (7.7 +/- 2.5 mg/L as an arithmetic mean and arithmetic standard deviation) and women (8.1 +/- 2.9 mg/L) in Japan, and no difference between the urban (2.3 +/- 0.8 mg/L) and rural women (2.6 +/- 1.1 mg/L) in China, the difference between Japanese (8.1 +/- 2.9 mg/L) and Chinese women (2.3 +/- 0.8 mg/L for two cities and 2.6 +/- 1.1 mg/L for two villages) was substantial. A literature survey suggested variation in dietary habits, especially that in sea algae intake, is a possible factor affecting the observed difference in Br-U between the two ethnic groups. Contribution of Br in cereals after fumigation with, e.g., methyl bromide, was also thought to be possible. The implication of difference in background Br-U levels is discussed in relation to biological monitoring of exposure to Br-containing industrial chemicals, such as 1- and 2-bromopropane.

Adult↗
PubMed2001

Systemic sclerosis complicated with nephrotic syndrome: relevance with antiribosomal P antibody.

The nephrotic syndrome is an extremely rare occurrence in systemic sclerosis (SSc). Here we describe a 39-year-old woman with SSc who developed the nephrotic syndrome along with the expression of antiribosomal P antibody but not of anti-double-stranded DNA antibody in her serum. Although a renal biopsy specimen showed minimal changes on light microscopy, immunofluorescence studies showed granular deposition of C3 and IgM in the glomeruli. The patient recovered from the nephrotic syndrome with the decrease in serum antiribosomal P antibody after the daily administration of 60 mg of prednisolone. It is strongly suggested that antiribosomal P antibody might have been involved in the development of the nephrotic syndrome in our patient.

Administration, Oral↗
PubMed2001

Amyloid angiopathy and variability in amyloid beta deposition is determined by mutation position in presenilin-1-linked Alzheimer's disease.

The presenilins (PSs) are components of large molecular complexes that contain beta-catenin and function as gamma-secretase. We report here a striking correlation between amyloid angiopathy and the location of mutation in PS-1 linked Alzheimer's disease. The amount of amyloid beta protein, Abeta(42(43)), but not Abeta(40,) deposited in the frontal cortex of the brain is increased in 54 cases of early-onset familial Alzheimer's disease, encompassing 25 mutations in the presenilin-1 (PS-1) gene, compared to sporadic Alzheimer's disease. The amount of Abeta(40) in PS-1 Alzheimer's disease varied according to the copy number of epsilon4 alleles of the Apolipoprotein E gene. Although the amounts of Abeta(40) and Abeta(42(43)) deposited did not correlate with the genetic location of the mutation in a strict linear sense, the histological profile did so vary. Cases with mutations between codon 1 and 200 showed, in frontal cortex, many diffuse plaques, few cored plaques, and mild or moderate amyloid angiopathy. Cases with mutations occurring after codon 200 also showed many diffuse plaques, but the number and size of cored plaques were increased (even when epsilon4 allele was not present) and these were often clustered around blood vessels severely affected by amyloid angiopathy. Similarly, diverging histological profiles, mainly according to the degree of amyloid angiopathy, were seen in the cerebellum. Mutations in the PS-1 gene may therefore alter the topology of the PS-1 protein so as to favor Abeta formation and deposition, generally, but also to facilitate amyloid angiopathy particularly in cases in which the mutation lies beyond codon 200. Finally we report that the amount of Abeta(42(43)) deposited in the brain correlated with the amount of this produced in culture by cells bearing the equivalent mutations.

Adult↗
PubMed2001

Diverse differentiation in malignant peripheral nerve sheath tumours associated with neurofibromatosis-1: an immunohistochemical and ultrastructural study.

AIMS: The diverse histological features in malignant peripheral nerve sheath tumours (MPNSTs) associated with NF-1 were investigated by immunohistochemical and electron microscopic analysis. Our study is focused on the differentiation of the tumour cells in the heterogeneous components. METHODS AND RESULTS: Twenty-three cases were classified as conventional type, epithelioid type, anaplastic type, and heterogeneous type, and divided into three groups by the presence of S100 protein (S100)-positive cells in each tumour; Group A was defined as having >50% S100+ cells, Group B as having <50%, and Group C as cases with no positive cells. To investigate the differentiation of the tumour cells, the morphology and immunoreactivity for neural or mesenchymal markers among the three groups were compared. For the identification of Schwannian, perineurial, and endoneurial differentiation, markers for S100, EMA and CD34 were used, respectively. In three tumours of the Group A type, there were no cases showing differentiation towards perineurial or endoneurial cells, or formation of heterogeneous components. In nine tumours of the Group B type, one tumour expressed EMA and CD34, suggesting probable perineurial and/or endoneurial differentiation. One tumour showed rhabdomyoblastic differentiation. Three tumours showed cartilaginous or osteogenic differentiation, and one of the three also showed a focal vascular differentiation. The surrounding areas of the heterogeneous components were composed of mixed S100+ cells and S100- cells. S100- cells in the areas were positive for CD34 in one case. In 11 tumours of Group C type, one tumour expressed EMA and CD34 suggesting perineurial and/or endoneurial cell differentiation. Three tumours showed rhabdomyoblastic differentiation. The tumour cells around the heterogeneous components in the three cases were negative for EMA and CD34. CONCLUSION: Our results suggest that tumour cells differentiating to Schwann cells are not the only component of MPNSTs. Furthermore, tumour cells other than Schwann cells are largely related to the formation of the heterogeneous components in MPNSTs associated with NF-1.

Adult↗
PubMed2001

Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin-1 gene show an unusual but characteristic beta-amyloid pathology known as 'cotton wool' plaques.

The pattern of deposition of amyloid beta protein (Abeta) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C-terminal species Abeta40 and Abeta42(43), in six cases of Alzheimer's disease (AD) due to deletions in exon 9 of PS-1 gene. These cases are characterized histologically by the presence of very large rounded plaques within the frontal cortex, known as 'cotton wool' plaques, composed of both Abeta40 and Abeta42(43) that are relatively free from neuritic changes and glial cell components, and usually devoid of a compact amyloid core. In the cerebellum the plaques are almost entirely of a compact type, again composed of Abeta40 and Abeta42(43), with only few diffuse Abeta42(43) containing plaques. The area fraction of Abeta40, and the ratio between Abeta40 and Abeta42(43), in frontal cortex was significantly higher than that seen in other cases of AD due to different PS-1 mutations, or in cases of sporadic AD, all of similar APO E genotype. The area fractions of Abeta42(43), however, did not significantly differ between these three groups. The unusual nature of the Abeta deposition in these cases may reflect the uniqueness of the mutation, which results in a failure to constitutively cleave the PS-1 holoprotein into its active form, and the effect this might have on APP trafficking and catabolism.

Adult↗