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Biomedical subjects

T Matsuda

Publications and source records attributed to T Matsuda.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of recombinant human soluble thrombomodulin (ART-123) in disseminated intravascular coagulation: results of a phase III, randomized, double-blind clinical trial.

BACKGROUND: Soluble thrombomodulin is a promising therapeutic natural anticoagulant that is comparable to antithrombin, tissue factor pathway inhibitor and activated protein C. OBJECTIVES: We conducted a multicenter, double-blind, randomized, parallel-group trial to compare the efficacy and safety of recombinant human soluble thrombomodulin (ART-123) to those of low-dose heparin for the treatment of disseminated intravascular coagulation (DIC) associated with hematologic malignancy or infection. METHODS: DIC patients (n = 234) were assigned to receive ART-123 (0.06 mg kg(-1) for 30 min, once daily) or heparin sodium (8 U kg(-1) h(-1) for 24 h) for 6 days, using a double-dummy method. The primary efficacy endpoint was DIC resolution rate. The secondary endpoints included clinical course of bleeding symptoms and mortality rate at 28 days. RESULTS: DIC was resolved in 66.1% of the ART-123 group, as compared with 49.9% of the heparin group [difference 16.2%; 95% confidence interval (CI) 3.3-29.1]. Patients in the ART-123 group also showed more marked improvement in clinical course of bleeding symptoms (P = 0.0271). The incidence of bleeding-related adverse events up to 7 days after the start of infusion was lower in the ART-123 group than in the heparin group (43.1% vs. 56.5%, P = 0.0487). CONCLUSIONS: When compared with heparin therapy, ART-123 therapy more significantly improves DIC and alleviates bleeding symptoms in DIC patients.

Aged↗
PubMed2006

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

Adult↗
PubMed2006

Surface phase transition of C12E1 at the air/water interface: a study by dynamic surface tension, external RA FT-IR, and 2D IR correlation methods.

The surface conformational states of the Gibbs monolayer of ethylene glycol mono-n-dodecyl ether (C(12)E(1)) at the air/water interface was studied using dynamic surface tension, external reflection-absorption FT-IR spectroscopy (ERA FT-IR), and two-dimensional infrared (2D IR) correlation methods at constant temperature. The dynamic surface tensions were measured at different bulk concentrations of C(12)E(1), and it was observed that a constant surface tension region appears at approximately 38.5 mN m(-1) in a dynamic surface tension profile at concentrations higher than 11 micromol kg(-1). This constant surface tension region corresponds to the surface phase transition from liquid expanded (LE) to liquid condensed (LC). Two sets of ERA FT-IR spectra were collected, one at different bulk concentrations but after equilibrium time (equilibrium measurements) and another at constant bulk concentration (m = 16 micromol kg(-1)) but at different times (dynamic measurements). The first set of these measurements show that the peak area increases in the range of 11 < m < or = 16 micromol kg(-1), which means the increase in the number of surfactant molecules at the air/water interface. Also, the wavenumber of antisymmetric CH(2) stretching decreases gradually from approximately 2923 cm(-1) (for 10 and 11 micromol kg(-1)) to approximately 2918 cm(-1) (for m > or = 16 micromol kg(-1)) with increasing concentration. The wavenumbers of 2923 and 2918 cm(-1) were assigned to LE and LC phases, respectively, and the decrease of wavenumber in the concentration range of 11 < m < or = 16 micromol kg(-1) were correlated to the surface phase transition (LE --> LC), or in other words, in the mentioned concentration range, two phases coexist. The dynamic ERA FT-IR measurements at 16 micromol kg(-1) also confirm the surface phase transition from LE to LC. The 2D IR correlation method was applied to the both equilibrium and dynamic IR spectra of the C(12)E(1) monolayer. The synchronous correlation maps show two strong autopeaks at approximately 2922 and approximately 2851 cm(-1) and also show a strong correlation (cross-peaks) between antisymmetric CH(2) stretching (nu(a)) and symmetric CH(2) stretching (nu(s)). The asynchronous correlation maps show that both observed bands of nu(a) and nu(s) in one-dimensional IR split into two components with the characteristic of overlapped bands, which reveals the coexistence of two phases (LE and LC) at the interface at 11 < m < or = 16 micromol kg(-1). The synchronous and asynchronous maps that were obtained from dynamic IR spectra closely resembled the equilibrium map.

Journal Article↗
PubMed2006

Differential cross section and photon-beam asymmetry for the gamma n --> K+ Sigma- reaction at E gamma = 1.5-2.4 GeV.

Differential cross sections and photon-beam asymmetries have been measured for the gamma n --> K+ Sigma- and gamma p --> K+Sigma0 reactions separately using liquid deuterium and hydrogen targets with incident linearly polarized photon beams of E gamma = 1.5-2.4 GeV at 0.6 < cos ThetacmK< 1. The cross section ratio of sigma K+ Sigma-/sigma K+ Sigma0, expected to be 2 on the basis of the isospin 1/2 exchange, is found to be close to 1. For the K+ Sigma- reaction, large positive asymmetries are observed, indicating the dominance of K* exchange. The large difference between the asymmetries for the K+ Sigma- and K+ Sigma0 reactions cannot be explained by simple theoretical considerations based on Regge model calculations.

Journal Article↗
PubMed2006

Relationship between apical membrane elasticity and stress fiber organization in fibroblasts analyzed by fluorescence and atomic force microscopy.

To investigate the relationship between cellular microelasticity and the structural features of cytoskeletons (CSKs), a microindentation test for apical cell membranes and observation of the spatio-distribution of actin CSKs of fibroblasts were performed by fluorescence and atomic force microscopy (FM/AFM). The indentation depths of apical cell membranes were measured from AFM force-indentation (f-i) curves under equal final loads and mapped two-dimensionally to show the relative distribution of local microelasticity on cell membranes. Intracellular spatial distribution of actin CSKs was visualized fluorescently by high Z-resolution cross-sectional observation of a cell on which indentation mapping analysis had been performed in advance. Structural features of stress fibers (SFs) were observed as three typical patterns of dense SF, sparse SF and sparser SF cell groups, which were quantitated using the degree of orientation in apical SFs (ASFs) that had been defined using two-dimensional Fourier analysis. In indentation depth maps, the upper nuclear region was markedly softer than the pseudopodium region. The mean indentation depth of the upper nuclear region decreased with increased SF density in whole cells and the degree of orientation of ASF, although the pseudopodium region did not exhibit such a trend. The apical membrane of adhered cells was found to tend to stiffen with the increase in both density and degree of orientation of SFs.

Actins↗
PubMed2006

Contribution of reverse Na+-Ca2+ exchange to spontaneous activity in interstitial cells of Cajal in the rabbit urethra.

Interstitial cells of Cajal (ICC) isolated from the rabbit urethra exhibit regular Ca2+ oscillations that are associated with spontaneous transient inward currents (STICs) recorded under voltage clamp. Their frequency is known to be very sensitive to external Ca2+ concentration but the mechanism of this has yet to be elucidated. In the present study experiments were performed to assess the role of Na+-Ca2+ exchange (NCX) in this process. Membrane currents were recorded using the patch clamp technique and measurements of intracellular Ca2+ were made using fast confocal microscopy. When reverse mode NCX was enhanced by decreasing the external Na+ concentration [Na+]o from 130 to 13 mM, the frequency of global Ca2+ oscillations and STICs increased. Conversely, inhibition of reverse mode NCX by KB-R7943 and SEA0400 decreased the frequency of Ca2+ oscillations and STICs. Application of caffeine (10 mM) and noradrenaline (10 microM) induced transient Ca2+-activated chloride currents (I(ClCa)) at -60 mV due to release of Ca2+ from ryanodine- and inositol trisphosphate (IP3)-sensitive Ca2+ stores, respectively, but these responses were not blocked by KB-R7943 or SEA0400 suggesting that neither drug blocked Ca2+-activated chloride channels or Ca2+ release from stores. Intact strips of rabbit urethra smooth muscle develop spontaneous myogenic tone. This tone was relaxed by application of SEA0400 in a concentration-dependent fashion. Finally, single cell RT-PCR experiments revealed that isolated ICC from the rabbit urethra only express the type 3 isoform of the Na+-Ca2+ exchanger (NCX3). These results suggest that frequency of spontaneous activity in urethral ICC can be modulated by Ca2+ entry via reverse NCX.

Action Potentials↗
PubMed2006

Endoscopic indications for endoscopic mucosal resection of laterally spreading tumours in the colorectum.

BACKGROUND: Laterally spreading tumours (LSTs) in the colorectum are usually removed by endoscopic mucosal resection (EMR) even when large in size. LSTs with deeper submucosal (sm) invasion, however, should not be treated by EMR because of the higher risk of lymph node metastasis. AIMS: To determine which endoscopic criteria, including high magnification pit pattern analysis, are associated with sm invasion in LSTs and clarify indications for EMR. METHODS: Eight endoscopic criteria from 511 colorectal LSTs (granular type (LST-G type); non-granular type (LST-NG type)) were evaluated retrospectively for association with sm invasion, and compared with histopathological findings. RESULTS: LST-NG type had a significantly higher frequency of sm invasion than LST-G type (14% v 7%; p<0.01). Presence of a large nodule in LST-G type was associated with higher sm invasion while pit pattern (invasive pattern), sclerous wall change, and larger tumour size were significantly associated with higher sm invasion in LST-NG type. In 19 LST-G type with sm invasion, sm penetration determined histopathologically occurred under the largest nodules (84%; 16/19) and depressed areas (16%; 3/19). Deepest sm penetration in 32 LST-NG type was either under depressed areas (72%; 23/32) or lymph follicular or multifocal sm invasion (28%; 1/32 and 8/32, respectively). CONCLUSIONS: When considering the most suitable therapeutic strategy for LST-G type, we recommend endoscopic piecemeal resection with the area including the large nodule resected first. In contrast, LST-NG type should be removed en bloc because of the higher potential for malignancy and greater difficulty in diagnosing sm depth and extent of invasion compared with LST-G type.

Colonoscopy↗
PubMed2006

Regulation of STAT3-mediated signaling by LMW-DSP2.

Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors, and has been reported to be constitutively activated in numerous cancer cells. In this study, we examined whether low molecular weight-dual specificity phosphatase two (LMW-DSP2) is involved in the regulation of the interleukin 6 (IL-6)/leukemia inhibitory factor (LIF)/STAT3-mediated signaling pathway. IL-6/LIF-induced LMW-DSP2 expression in murine testicular or hepatoma cell lines, while LMW-DSP2 overexpression in 293T cells suppressed IL-6-induced phosphorylation and activation of STAT3. Furthermore, LMW-DSP2 suppressed the expression of IL-6-induced endogenous genes. In contrast, small-interfering RNA-mediated reduction of LMW-DSP2 expression enhanced IL-6-induced STAT3-dependent transcription. In fact, LMW-DSP2 interacted with STAT3 in vivo and endogenous LMW-DSP2 bound to STAT3 in murine testicular GC-1 cells. These results strongly suggest that LMW-DSP2 acts as a negative regulator of the IL-6/LIF/STAT3-mediated signaling pathway.

Animals↗
PubMed2006

Mechanical compressive loading stimulates the activity of proximal region of human COL2A1 gene promoter in transfected chondrocytes.

Previous studies have demonstrated that the mechanical compressive loading affects the biosynthesis of chondrocytes seeded in three dimensional scaffolds. In this study, the level of type II collagen mRNA expression was increased by a continuous dynamic compression at 10% compressive strain and 0.1 Hz in chondrocytes seeded in a biodegradable, elastomeric scaffold, poly(L-lactide-co-epsilon-caprolactone) (PLCL). To further examine this molecular mechanism, the promoter region of COL2A1 gene, which is encoding type II collagen, was analyzed using rabbit chondrocytes transfected with luciferase reporter vectors containing the 5'-flanking regions of human COL2A1 gene. A deletion mutant analysis revealed that the most active short promoter in response to continuous dynamic compression is in the region between -509 and -109 base pairs, where the transcription factor Sp1 is located. Additionally, an mRNA decay experiment using transcription inhibitor actinomycin D demonstrated that dynamic compression do not stabilize type II collagen mRNA. Our results indicate that mechanical compression increases the level of type II mRNA expression by transcriptional activation possibly through the Sp1 binding sites residing in the proximal region of the COL2A1 gene promoter.

Animals↗
PubMed2006

Phthalocyanine-dyed fibers adsorb allergenic proteins.

Phthalocyanine (Pc)-dyed fiber is reported to reduce atopic symptoms in some patients when they use underwear made of the fiber. We investigated the adsorption of allergens on Pc-fiber. Pc-fiber trapped house dust/pollen/food allergens with varied molecular weight and pI. The adsorbed allergens were released in the presence of mild detergent. Pc-fiber did not change the molecular weight or disulfide bonding of the allergens. These observations imply that Pc-fiber is applicable as an "allergen trap" for a wide variety of products.

Adsorption↗
PubMed2006

Physical and functional interactions between Daxx and STAT3.

Signal transducer and activator of transcription 3 (STAT3) play key roles in the intracellular signaling pathways of the interleukin (IL)-6 family of cytokines, which exhibit a diverse set of cellular responses, including cell proliferation and differentiation. Dysregulated IL-6/STAT3 signaling is involved in the pathogenesis of several diseases, for example autoimmune diseases and tumors. Type I interferon (IFN) induces the expression of proapoptotic genes and has been used in the clinical treatment of several tumors. In the present study, we found that type I IFN suppressed IL-6/STAT3-mediated transcription and gene expression. Furthermore, a type I IFN-induced protein, Daxx, also suppressed STAT3-mediated transcriptional activation, while overexpression of Daxx inhibited IL-6/STAT3-mediated gene expression. Importantly, small-interfering RNA-mediated reduction of Daxx expression enhanced IL-6/leukemia inhibitory factor (LIF)-induced STAT3-dependent transcription. Co-immunoprecipitation studies revealed a physical interaction between Daxx and STAT3 in transiently transfected 293T cells. We further found that Daxx and STAT3 were co-localized in the nucleus. These results indicate that Daxx may serve as a transcriptional regulator of type I IFN-mediated suppression of the IL-6/STAT3 signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Detection and identification of dyes showing AhR-binding affinity in treated sewage effluents.

A bioassay using the YCM3 recombinant yeast strain was utilised to investigate the presence of dioxin-like compounds that activate the aryl hydrocarbon receptor (AhR) in treated sewage effluents. AhR ligand activity was detected in the concentrated extracts of effluent samples collected in March, June and October 2004 from Kyoto city, Japan. HPLC fractionation was carried out using C18 reversed-phase columns, and possible AhR ligands were further isolated and purified. By using LC/MS/MS, one weak AhR ligand was identified to be rhodamine B base, a fluoran dye. In addition, two other coloured ligands were postulated to be disperse anthraquinone dyes or their metabolites because of their UV spectra and HPLC retention times. The AhR-binding affinities of 12 commercial dyes with different chemical structures were also studied. Among the dyes tested, hydrophobic anthraquinone dyes exhibited higher AhR ligand activity, but azo dyes or hydrophilic acid dyes showed no or very low AhR ligand activity. Rhodamine B base and disperse anthraquinone dyes were suggested to be potential xenobiotic AhR ligands. Future research regarding their contamination in aquatic environments and toxicological information is necessary.

Biological Assay↗
PubMed2006

Predicting struvite formation for phosphorus recovery from human urine using an equilibrium model.

Interest in phosphorus recovery from urine diverted from faeces has been growing recently. Phosphorus in urine can be precipitated out as struvite (MgNH4PO4 x 6H2O) with addition of magnesium salt under alkaline conditions. Struvite formation, however, should be more well understood for its practical application. We predicted the struvite formation with a development of a new equilibrium model. The model considered the formation of eight different kinds of precipitates, including struvite, with effects of ionic strength and temperature. In addition, experiments on struvite formation in urine were conducted for the model validation. The model prediction of struvite formation had good agreement with the experimental results. The optimum pH to form struvite was predicted to be 9.4-9.7. In order to precipitate 99% of phosphate in urine with 1.5 fold Mg concentration to PO4-P, the pH value was necessary to be more than 8.1 based on the model prediction.

Humans↗
PubMed2006

Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

Administration, Topical↗
PubMed2005

Near-threshold diffractive psi-meson photoproduction from the proton.

Photoproduction of a phi meson on protons was studied by means of linearly polarized photons at forward angles in the low-energy region from threshold to Egamma = 2.37 GeV. The differential cross sections at t = -|t|min do not increase smoothly as Egamma increases but show a local maximum at around 2.0 GeV. The angular distributions demonstrate that phi mesons are photoproduced predominantly by helicity-conserving processes, and the local maximum is not likely due to unnatural-parity processes.

Journal Article↗
PubMed2005

Endothelins stimulate the expression of neurotrophin-3 in rat brain and rat cultured astrocytes.

Endothelins play a role in the regulation of astrocytic functions in brain pathologies such as hyperplasia and neurotrophic factor production. The present study examined the effects of endothelins on production of neurotrophin-3, a member of the neurotrophin family of neurotrophic factors, in cultured astrocytes and rat brain. Quantitative reverse transcription-PCR analysis of mRNA copy numbers showed that cultured astrocytes expressed comparable numbers of neurotrophin-3 and neurotrophin-4/5 mRNA copies to nerve growth factor and brain-derived neurotrophic factor. Endothelin-1 (100 nM) and Ala1,3,11,15-endothelin-1 (an endothelinB receptor agonist, 100 nM) caused a transient increase in neurotrophin-3 mRNA levels, but not in neurotrophin-4/5 levels, in cultured astrocytes. The increases in mRNA levels were accompanied with that in extracellular release of neurotrophin-3. The effects of endothelin-1 on neurotrophin-3 mRNA levels were reduced by BQ788, an endothelinB receptor antagonist. I.c.v. administration of 500 pmol/day Ala1,3,11,15-endothelin-1 increased mRNA and peptide levels of neurotrophin-3 in rat caudate putamen and cerebrum. On the other hand, neurotrophin-3 production in hippocampus was not affected by Ala1,3,11,15-endothelin-1. Immunohistochemical examination of Ala1,3,11,15-endothelin-1-infused rats showed that neurotrophin-3 was mainly expressed in glial fibrillary acidic protein-positive astrocytes in caudate putamen and cerebrum. endothelin-induced increases in neurotrophin-3 expression in cultured astrocytes were inhibited by chelation of intracellular Ca2+ and PD98095 (an ERK inhibitor). These results suggest that endothelin is an extracellular signal that stimulates astrocytic neurotrophin-3 production in brain pathologies.

Animals↗