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Biomedical subjects

Takuya Matsumoto

Publications and source records attributed to Takuya Matsumoto.

At least 19 recordsLinked to original sources
PubMed2006

Prediction of strength and strain of the proximal femur by a CT-based finite element method.

Hip fractures are the most serious complication of osteoporosis and have been recognized as a major public health problem. In elderly persons, hip fractures occur as a result of increased fragility of the proximal femur due to osteoporosis. It is essential to precisely quantify the strength of the proximal femur in order to estimate the fracture risk and plan preventive interventions. CT-based finite element analysis could possibly achieve precise assessment of the strength of the proximal femur. The purpose of this study was to create a simulation model that could accurately predict the strength and surface strains of the proximal femur using a CT-based finite element method and to verify the accuracy of our model by load testing using fresh frozen cadaver specimens. Eleven right femora were collected. The axial CT scans of the proximal femora were obtained with a calibration phantom, from which the 3D finite element models were constructed. Materially nonlinear finite element analyses were performed. The yield and fracture loads were calculated, while the sites where elements failed and the distributions of the principal strains were determined. The strain gauges were attached to the proximal femoral surfaces. A quasi-static compression test of each femur was conducted. The yield loads, fracture loads and principal strains of the prediction significantly correlated with those measured (r=0.941, 0.979, 0.963). Finite element analysis showed that the solid elements and shell elements in undergoing compressive failure were at the same subcapital region as the experimental fracture site.

Adult↗
PubMed2006

The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations.

Multidrug and toxic compound extrusion (MATE) proteins, comprising the most recently designated family of multidrug transporter proteins, are widely distributed in all kingdoms of living organisms, although their function is far from understood. The bacterial MATE-type transporters that have been characterized function as exporters of cationic drugs, such as norfloxacin and ethidium, through H(+) or Na(+) exchange. Plant MATE-type transporters are involved in the detoxification of secondary metabolites, including alkaloids. Mammalian MATE-type transporters are responsible for the final step in the excretion of metabolic waste and xenobiotic organic cations in the kidney and liver through electroneutral exchange of H(+). Thus, we propose that members of the MATE family are organic cation exporters that excrete metabolic or xenobiotic organic cations from the body.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2006

The sleep-enhancing effect of valerian inhalation and sleep-shortening effect of lemon inhalation.

We examined the effects of odorant inhalation on the sleep-wake states in rats. Odorants used in the experiment were clove, jasmine, lavender, lemon, peppermint, pine, rose, sandalwood, valerian, and ylang-ylang. Valerian and rose inhalation significantly prolonged the pentobarbital-induced sleeping time, whereas lemon inhalation significantly shortened it. The effect of valerian inhalation was markedly noticeable. In the anosmic rats, a significant effect of odorants on the pentobarbital sleep time was not seen. Electroencephalographic studies on natural sleep revealed that rose inhalation did not exert any significant effect on sleep, but a significant shortening in sleep latency and a significant prolonging in total sleep time were observed with valerian inhalation, whereas a significant prolonging in sleep latency was observed with lemon inhalation. Such effects of valerian and lemon inhalation were not admitted in anosmic rats. gamma-Aminobutyric acid (GABA) transaminase assay indicates that valerian inhalation decreases the activity of the enzyme and enhances GABA activity. Although valerian has been reported to exert a good effect for sleep as a medicine for internal use, the present study is the first medical report suggesting that the inhalation of valerian may enhance the sleep. On the other hand, the present results may suggest the possibility that lemon inhalation may cause a worsening of insomnia symptoms.

Animals↗
PubMed2006

Wide variety of locations for rodent MATE1, a transporter protein that mediates the final excretion step for toxic organic cations.

MATE1 was the first mammalian example of the multidrug and toxin extrusion (MATE) protein family to be identified. Human MATE1 (hMATE1) is predominantly expressed and localized to the luminal membranes of the urinary tubules and bile canaliculi and mediates H(+)-coupled electroneutral excretion of toxic organic cations (OCs) into urine and bile (Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, and Moriyama Y. Proc Natl Acad Sci USA 102: 17923-17928, 2005). mMATE1, a mouse MATE ortholog, is also predominantly expressed in kidney and liver, although its transport properties are not yet characterized. In the present study, we investigated the transport properties and localization of mMATE1. Upon expression of this protein in HEK-293 cells, mMATE1 mediated electroneutral H(+)/tetraethylammonium exchange and showed a substrate specificity similar to that of hMATE1. Immunological techniques with specific antibodies against mMATE1 combined with RT-PCR revealed that mMATE1 is also expressed in various cells, including brain glia-like cells and capillaries, pancreatic duct cells, urinary bladder epithelium, adrenal gland cortex, alpha cells of the islets of Langerhans, Leydig cells, and vitamin A-storing Ito cells. These results indicate that mMATE1 is a polyspecific H(+)/OC exchanger. The unexpectedly wide distribution of mMATE1 suggests involvement of this transporter protein in diverse biological functions other than excretion of OCs from the body.

Amino Acid Sequence↗
PubMed2006

A directly fused tetrameric porphyrin sheet and its anomalous electronic properties that arise from the planar cyclooctatetraene core.

Oxidation of a directly meso-meso linked cyclic porphyrin tetramer 2 gave a porphyrin sheet 3. The symmetric square structure of 3 is indicated by its simple 1H NMR spectrum that exhibits only two signals for the porphyrin beta-protons. The absorption spectrum of 3 displays characteristic Soret-like broad bands and weak Q-bands, and its magnetic circular dichroism (MCD) spectrum exhibits a negative Faraday A term at the 762 nm band as a rare case, indicating the absorption as a transition from a nondegenerate level to a degenerate level. A slightly longer S1-state (1.1 ps) and smaller TPA cross section (2750 GM) than a tetrameric linear porphyrin tape also indicate its unique electronic properties. The porphyrin sheet 3 forms stable 1:2 complexes with guest molecules G1 and G2, whose 1H NMR spectra exhibit remarkable downfield shifts for the guest protons that are located just above the cyclooctatetraene (COT) core of 3, whereas the imidazolyl protons bound to the zinc(II) porphyrin local cores are observed at slightly upfield positions. These results have been qualitatively accounted for in terms of the presence of a strong paratropic ring current around the COT core that propagates through the whole pi-electronic network of 3, hence competing with and cancelling the weak diatropic ring currents of the local zinc(II) porphyrins. This explanation was supported by DFT calculation performed at the GIAO-B3LYP/6-31G level, which indicated large positive NICS values within the COT core and small NICS values within the local zinc(II) porphyrins.

Journal Article↗
PubMed2006

Giant porphyrin wheels with large electronic coupling as models of light-harvesting photosynthetic antenna.

Starting from a 1,3-phenylene-linked diporphyrin zinc(II) complex 2ZA, repeated stepwise Ag(I)-promoted coupling reactions provided linear oligomers 4ZA, 6ZA, 8ZA, and 12ZA. The intramolecular cyclization reaction of 12ZA under dilute conditions (1x10(-6) M) gave porphyrin ring C12ZA with a diameter of approximately 35 A in 60% yield. This synthetic strategy has been applied to a 1,3-phenylene-linked tetraporphyrin 4ZB to provide 8ZB, 12ZB, 16ZB, 24ZB, and 32ZB. The intramolecular coupling reaction of 24ZB gave a larger 24-mer porphyrin ring C24ZB with a diameter of approximately 70 A in 34% yield. These two large porphyrin rings were characterized by means of 1H NMR spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy, UV-visible spectroscopy, gel permeation chromatography (GPC) analysis, and scanning tunneling microscopy (STM) techniques. The STM images of C12ZA reveal largely circular structures, whereas those of C24ZB exhibit mostly ellipsoidal shapes, indicating more conformational flexibility of C24ZB. Similar to the case of C12ZA, the efficient excitation energy transfer along the ring has been confirmed for C24ZB by using the time-correlated single-photon counting (TCSPC) and picosecond transient absorption anisotropy (TAA) measurements, and occurs with a rate of (35 ps)(-1) for energy hops between neighboring tetraporphyrin subunits. Collectively, the present work provides an important step for the construction of large cyclic-arranged porphyrin arrays with ample electronic interactions as a model of light-harvesting antenna.

Light-Harvesting Protein Complexes↗
PubMed2006

Cell instructive polymers.

Polymeric materials used in tissue engineering were initially used solely as delivery vehicles for transplanting cells. However, these materials are currently designed to actively regulate the resultant tissue structure and function. This control is achieved through spatial and temporal regulation of various cues (e.g., adhesion ligands, growth factors) provided to interacting cells from the material. These polymeric materials that control cell function and tissue formation are termed cell instructive polymers, and recent trends in their design are outlined in this chapter.

Animals↗
PubMed2006

Atomic force microscopic observation of Escherichia coli ribosomes in solution.

Ribosomes of Escherichia coli were visualized in buffer solution by atomic force microscopy (AFM). A series of time-dependent AFM images showed that ribosomes spontaneously adsorb on mica. Although ribosomes observed in air are forced to flatten on the surface, the height of ribosomal particles obtained under a physiological buffer solution is 21.8+/-0.5 nm, which is consistent with the ideal diameter. We succeeded in observing single ribosomes in a near-native condition.

Escherichia coli↗
PubMed2006

Role of acidic amino acid for regulating hydroxyapatite crystal growth.

Non-collagenous proteins in hard tissue matrix are thought to play a pivotal role in regulating the crystal growth of hydroxyapatite (HAp). As most non-collagenous proteins are acidic proteins containing acidic amino acid-rich sequences, we examined the growth of HAp crystals from HAp seed crystals in the presence/absence of acidic amino acid. New HAp formation generally started from the P-surface of HAp. However, in the presence of acidic amino acid, new HAp formation was observed on both P-surface and C-surface of HAp seed crystals. Furthermore, newly formed HAp showed specific orientation along the long-axis direction of HAp seed crystals. In terms of crystallinity, HAp formed in the presence of acidic amino acid showed low crystallinity. These results suggested that, in biomineralization, the adsorbed or free state of acidic amino acid would influence crystal formation and orientation as follows: 1) If free in solution, acidic amino acid would inhibit HAp crystal growth; 2) If adsorbed or immobilized on matrix, acidic amino acid would become HAp nucleation site and regulate the orientation of HAp crystals.

Amino Acids, Acidic↗
PubMed2005

A human transporter protein that mediates the final excretion step for toxic organic cations.

In mammals, toxic electrolytes of endogenous and exogenous origin are excreted through the urine and bile. Before excretion, these compounds cross numerous cellular membranes in a transporter-mediated manner. However, the protein transporters involved in the final excretion step are poorly understood. Here, we show that MATE1, a human and mouse orthologue of the multidrug and toxin extrusion family conferring multidrug resistance on bacteria, is primarily expressed in the kidney and liver, where it is localized to the luminal membranes of the urinary tubules and bile canaliculi. When expressed in HEK293 cells, MATE1 mediates H(+)-coupled electroneutral exchange of tetraethylammonium and 1-methyl-4-phenylpyridinium. Its substrate specificity is similar to those of renal and hepatic H(+)-coupled organic cations (OCs) export. Thus, MATE1 appears to be the long searched for polyspecific OC exporter that directly transports toxic OCs into urine and bile.

1-Methyl-4-phenylpyridinium↗
PubMed2005

Giant meso-meso-linked porphyrin arrays of micrometer molecular length and their fabrication.

On the basis of the Ag(I)-promoted coupling reaction of zinc(II)-5,15-bis(3,5-dioctyloxyphenyl)porphyrin Z1, chain elongation has been attempted by using a stepwise doubling approach, which provides Z2, Z4, Z8, Z16, Z32, Z64, Z128, Z256, Z384, and Z512. The porphyrin arrays up to Z128 are sufficiently soluble in CHCl3 and THF despite their very long molecular lengths and rodlike structures, while the arrays over Z128 show a significant drop in solubility and stability. The discrete porphyrin arrays thus isolated were characterized by means of (1)H NMR spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, UV/Vis spectroscopy, gel-permeation chromatography (GPC), cyclic voltammetry (CV), single-crystal X-ray crystallography, scanning tunneling microscopy (STM), and atomic force microscopy (AFM). Contrary to expected linear conformations of the arrays Z n (where n is the number of porphyrins), the single molecular images of Z128, Z256, and Z512 revealed largely bent structures; this finding indicates the substantial conformational flexibility of Z n. We also exploited an effective synthetic route by means of which Z n can be fabricated with a thiol-protected aryl group to provide Z n S(2) through Z n Br(2), by bromination with N-bromosuccinimide and subsequent Pd-catalyzed Suzuki-Miyaura arylation. Finally, the reaction of Z256 provided Z512, Z768, and Z1024. Collectively, this work provides an important milestone in the preparation of sub-microscale discrete organic molecules and the fabrication of molecular-based materials, hence significantly contributing to device applications.

Journal Article↗
PubMed2005

Non-viral gene delivery regulated by stiffness of cell adhesion substrates.

Non-viral gene vectors are commonly used for gene therapy owing to safety concerns with viral vectors. However, non-viral vectors are plagued by low levels of gene transfection and cellular expression. Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector, whereas the influence of the cellular environment in DNA uptake is often ignored. The mechanical properties (for example, rigidity) of the substrate to which a cell adheres have been found to mediate many aspects of cell function including proliferation, migration and differentiation, and this suggests that the mechanics of the adhesion substrate may regulate a cell's ability to uptake exogeneous signalling molecules. In this report, we present a critical role for the rigidity of the cell adhesion substrate on the level of gene transfer and expression. The mechanism relates to material control over cell proliferation, and was investigated using a fluorescent resonance energy transfer (FRET) technique. This study provides a new material-based control point for non-viral gene therapy.

3T3 Cells↗
PubMed2005

Directly meso-meso linked porphyrin rings: synthesis, characterization, and efficient excitation energy hopping.

Directly meso-meso linked porphyrin rings CZ4, CZ6, and CZ8 that respectively comprise four, six, and eight porphyrins have been synthesized in a stepwise manner from a 5,10-diaryl zinc(II) porphyrin building block. Symmetric cyclic structures have been indicated by their very simple (1)H NMR spectra that exhibit only a single set of porphyrin and their absorption spectra that display a characteristic broad nonsplit Soret band around 460 nm. Energy minimized structures calculated at the B3LYP/6-31G* level indicate that a dihedral angle between neighboring porphyrins decreases in order of CZ6 > CZ8 > CZ4, which is consistent with the (1)H NMR data. Photophysical properties of these molecules have been examined by the steady-state absorption, fluorescence, fluorescence lifetime, fluorescence anisotropy decay, and transient absorption measurements. Both the pump-power dependence on the femtosecond transient absorption and the transient absorption anisotropy decay profiles are directly related with the excitation energy migration processes within the porphyrin rings, where the exciton-exciton annihilation time and the polarization anisotropy rise time are well described in terms of the Forster-type incoherent energy hopping model. Consequently, the excitation energy hopping rates have been estimated for CZ4 (119 +/- 2 fs)(-)(1), CZ6 (342 +/- 59 fs)(-)(1), and CZ8 (236 +/- 31 fs)(-)(1), which reflect the magnitude of the electronic coupling between the neighboring porphyrins. Overall, these porphyrin rings serve as a well-defined wheel-shaped light harvesting antenna model in light of very efficient excitation energy hopping along the ring.

Journal Article↗
PubMed2005

Ex vivo electroporation as a potent new strategy for nonviral gene transfer into autologous vein grafts.

Gene transfer to vein grafts has therapeutic potential to prevent late graft failure; however, certain issues, including efficacy and safety, have hindered the clinical application of this treatment modality. Here, we report the successful and efficient gene transfer of plasmid DNA via ex vivo electroporation into veins as well as into vein grafts. Two approaches were used: one involved transluminal in situ gene transfer using a T-shaped electrode (the "Lu" method), and the other was an adventitial ex vivo approach using an electroporation cuvette followed by vein grafting (the "Ad" method). The Lu method was carried out at 10 V, with optimal gene transfer efficiency in the in situ jugular veins of rabbits, and transgene expression was observed primarily in endothelial cells. However, when these veins were grafted into the arterial circulation, no luciferase activity was detected; this effect was probably due to the elimination of the gene-transferred cells as a result of endothelial denudation. In contrast, optimal and satisfactory gene transfer was obtained with the vein grafts subjected to the Ad method at 30 V, and transgene expression was seen primarily in adventitial fibroblasts. Gene transfer of endothelial nitric oxide synthase cDNA to the vein graft via the Ad method successfully limited the extent of intimal hyperplasia, even under hyperlipidemic conditions, at 4 wk after grafting. We thus propose that the Ad method via ex vivo electroporation may provide a novel, safe, and clinically available technique for nonviral gene transfer to sufficiently prevent late graft failure.

Animals↗
PubMed2005

Leukemoid reaction in association with bone marrow necrosis due to metastatic prostate cancer.

An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8 x 10(3)/microl. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-alpha were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved.

Aged↗
PubMed2005

Advantages of TOF-SIMS analysis of hydroxyapatite and fluorapatite in comparison with XRD, HR-TEM and FT-IR.

The chemical analysis of hydroxyapatite and fluorapatite was carried out using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Hydroxyapatite and fluorapatite were synthesized at 80 +/- 1 degrees C and pH 7.4 +/- 0.2. Fluorapatite was better crystallized, with its (300) reflection shifted to a slightly higher angle. High-resolution transmission electron microscopy clearly revealed a typical, regular hexagonal cross section perpendicular to the c-axis for fluorapatite and a flattened hexagonal cross section for hydroxyapatite. FT-IR spectra of fluorapatite confirmed the absence of OH absorption peak--which was seen in hydroxyapatite at about 3570 cm(-1). TOF-SIMS mass spectra showed a peak at 40 amu due to calcium. In addition, a peak at 19 amu due to fluorine could be clearly seen, although the intensities of PO, PO2, and PO3 were very low. It was confirmed that TOF-SIMS clearly showed the differences between positive and negative mass spectra of hydroxyapatite and fluorapatite, especially for F-. We concluded that TOF-SIMS exhibited distinct advantages compared with other methods of analysis.

Apatites↗
PubMed2004

Ferrimagnetic ordering due to Fe(III) d and donor pi spins in (ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide)2.FeBr4.

Magnetization and heat capacity were measured down to 0.4 K in a 2:1 charge-transfer (CT) salt of a new donor molecule, ethylenedithiotetrathiafulvalenoquinone-1,3-dithiolemethide (1) with a magnetic FeBr(4)(-) ion (1(2).FeBr(4)). The Fe(III) d spins of FeBr(4)(-) ions were subject to apparently ferromagnetic interaction with each other through the interaction with the pi spins developed by localization of the conducting pi electrons on the donor columns, eventually giving rise to ferrimagnetic ordering (FI) near 1 K, which provides the first example in a molecular pi-d system.

Journal Article↗