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Biomedical subjects

Tetsuya Ishikawa

Publications and source records attributed to Tetsuya Ishikawa.

At least 19 recordsLinked to original sources

Three-dimensional GaN-Ga2O3 core shell structure revealed by x-ray diffraction microscopy.

In combination of direct phase retrieval of coherent x-ray diffraction patterns with a novel tomographic reconstruction algorithm, we, for the first time, carried out quantitative 3D imaging of a heat-treated GaN particle with each voxel corresponding to 17 x 17 x 17 nm3. We observed the platelet structure of GaN and the formation of small islands on the surface of the platelets, and successfully captured the internal GaN-Ga2O3 core shell structure in three dimensions. This work opens the door for nondestructive and quantitative imaging of 3D morphology and 3D internal structure of a wide range of materials at the nanometer scale resolution that are amorphous or possess only short-range atomic organization.

Journal Article↗

Single-shot spectrometry for x-ray free-electron lasers.

An experimental scheme to realize single-shot spectrometry for the diagnostics of x-ray free-electron lasers (XFELs) is presented. The combination of an ultraprecisely figured mirror and a perfect crystal form a simple, high-precision spectrometer that can cover an energy range from a few eV to a hundred eV with high resolution. The application of the spectrometer to determine XFEL pulse widths was investigated theoretically and experimentally. It has been shown that the present system can determine pulse widths from sub-fs to ps in a single shot even for spontaneous radiation. The system can be easily extended to even shorter pulses.

Journal Article↗

Stable top-up operation at SPring-8.

Top-up operation allows SPring-8 to provide highly stable X-ray beams with arbitrary filling patterns. The implementation of top-up operation is described, with a focus on the simultaneous achievement of stability of stored current, beam orbit, purity of an isolated single bunch, and beam injection efficiency. Stored-current fluctuations have been routinely reduced to a level of 10(-3). Stored-beam oscillation on frequent beam injection, which was originally regarded as the most serious problem, has been successfully suppressed to a sufficiently low level that it never perturbs imaging experiments. Current impurities in nominally empty buckets have been reduced to a level of 10(-9) over more than one week of operation, making possible the measurement of time-resolved spectra using high-current bunches. Finally, excellent injection efficiency, higher than 80%, is routinely obtained, even for small undulator gaps, which is critical for preventing radiation damage to insertion-device magnets and to reduce leakage radiation. The process of achieving highly stabilized top-up operation at SPring-8 and its utility for user experiments are described.

Electrons↗

Establishment of a functionally active collagen-binding vascular endothelial growth factor fusion protein in situ.

OBJECTIVE: Tissue regeneration requires both growth factor and extracellular matrix such as collagen, serving as a scaffold for cell growth. We established FNCBD-VEGF121, consisting of the fibronectin collagen-binding domain (FNCBD) and vascular endothelial growth factor (VEGF) 121, and investigated its properties. METHODS AND RESULTS: FNCBD-VEGF121 specifically bound to gelatin and type I, II, III, IV, and V collagen. This collagen-bound FNCBD-VEGF121 captured soluble VEGF receptor 2 (VEGFR-2)/Fc chimeric protein. Cell growth-promoting activity of FNCBD-VEGF121 was almost identical to that of VEGF121. The VEGF fusion protein significantly enhanced the expression of VEGFR-2 (71.6+/-0.8%) on endothelial progenitor cells (EPCs) derived from umbilical cord blood. Expectably, the collagen-bound VEGF fusion protein not only promoted the growth of endothelial cells (ECs) but also induced the expression of VEGFR-2 (63.7+/-0.8%) on non-adherent cells expanded from bone marrow CD34+ cells. Moreover, the VEGF fusion protein enhanced sprout formation of ECs in a matrigel model. In vivo experiments revealed that FNCBD-VEGF121 had local effects but not systemic effect on EPC mobilization. CONCLUSIONS: These results suggest that FNCBD-VEGF121 stably maintains an optimally high and local concentration of VEGF with collagen matrix and stimulates both ECs and EPCs in situ, supplying a vascular regeneration niche.

Antigens, CD34↗

Nearly perfect large-area quartz: 4 meV resolution for 10 keV photons over 10 cm(2).

The perfection of two commercial top-grade quartz crystal wafers has been investigated using Bragg reflection at theta(B)=89.77 degrees of a 2.0 meV bandwidth beam of 9.979 keV X-rays by the (7\bar4\bar34) lattice planes. Topographic images show small defect concentrations (<or=5 cm(-2)). Energy scan widths are below 3 meV over 8 mm x 8 mm areas and 4 meV over the whole wafer ( approximately 11 cm(2)). This suggests that quartz can be a useful optical material.

Journal Article↗

Acoustic pulse echoes probed with time-resolved X-ray triple-crystal diffractometry.

Acoustic pulse echoes generated by femtosecond laser irradiation were detected using time-resolved x-ray triple-crystal diffractometry. The determined time-dependent longitudinal strain component for pulse echoes in silicon and gallium arsenide plates showed that the polarity of the strain pulse was dependent on the optically induced initial stress, and that the bipolar pulse waveform was gradually deformed and broadened in the course of propagation. The three-dimensional wave front distortion of pulse echoes was shown simply as the pulse duration broadening, which was consistent with a boundary roughness for an unpolished plate.

Journal Article↗

Development of a scanning tunneling microscope for in situ experiments with a synchrotron radiation hard-X-ray microbeam.

A scanning tunneling microscope dedicated to in situ experiments under the irradiation of highly brilliant hard-X-rays of synchrotron radiation has been developed. In situ scanning tunneling microscopy (STM) observation was enabled by developing an accurate alignment system in ultrahigh vacuum. Despite the noisy conditions of the synchrotron radiation facility and the radiation load around the probe tip, STM images were successfully obtained at atomic resolution. Tip-current spectra were obtained for Ge nano-islands on a clean Si(111) surface by changing the incident photon energy across the Ge absorption edge. A current modification was detected at the absorption edge with a spatial resolution of the order of 10 nm.

Journal Article↗

Alteration of serum cytokine balances among different phases of chronic hepatitis B virus infection.

To understand the pathogenesis of chronic hepatitis B virus (HBV) infection, we examined the serum levels of IL-10, TNF-alpha IL-12 p70, and IL-12 p40 in 77 patients chronically infected with HBV and 19 controls. The patients were classified into four groups: asymptomatic carriers (ASC), patients with chronic hepatitis (CH), patients with liver cirrhosis (LC), and patients with hepatocellular carcinomas (HCC). The cytokine values among these groups were compared and their relations to clinical parameters were investigated. All these cytokine values were higher in the patient groups than in controls. IL-10 and TNF-alpha became higher in accordance with the progress of the disease phases, from ASC to LC, and lowest when the patients had HCC. IL-12 p40 was also lowest in HCC, however, the group with highest levels was CH. IL-12 p70 was unchanged among ASC, CH, and LC, but were raised in HCC. Serial analyses for the cytokine values in the same patients showed the similar tendencies. Regression analysis showed the significant correlations between ALT and IL-10. Serum cytokine values well reflected the pathological differences of the individual disease phases, and may become useful indices to understand the pathogenesis of chronic HBV infection.

Journal Article↗

The SHAP-hyaluronan complex in serum from patients with chronic liver diseases caused by hepatitis virus infection.

Our previous study suggested that the serum-derived hyaluronan associated protein (SHAP)-hyaluronan (HA) complex in the sera of patients with rheumatoid arthritis is useful as a marker that directly correlates with the degree of inflammation. Here, we have investigated the serum levels of the SHAP-HA complex in patients at various clinical stages of chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) caused by infection with the hepatitis C or hepatitis B virus. Both serum levels of the SHAP-HA complex and HA in those patients were significantly higher than those of the controls and increased in the order of CH<LC<HCC. Different from the HA levels, there was a significant difference in the SHAP-HA complex levels between the LC and HCC groups in both HBV- and HCV-infected patients. In addition, the serum level of the SHAP-HA complex correlated with the well-known biomarkers for liver injury and function such as albumin and platelet, including the HCC indicator alpha-fetoprotein. In conclusion, the present data suggest that the SHAP-HA complex level is a better indicator for the progression of the stages of liver fibrosis, and that it could be a marker for HCC, in both HBV- and HCV-infected patients.

Journal Article↗

Plasma amino acid profiles applied for diagnosis of advanced liver fibrosis in patients with chronic hepatitis C infection.

UNLABELLED: Although biopsy has been considered mandatory in diagnosing liver fibrosis, there is a high demand for alternative effective and noninvasive methods. In this study we aimed to develop a noninvasive and effective method using the plasma amino acid profiles for the diagnosis of liver fibrosis. MATERIALS AND METHODS: Fifty-three patients with chronic hepatitis C infection were included in the study. Plasma amino acid concentration was analyzed and severity of fibrosis was staged based on biopsy. We employed a previously published amino acid-based approach to develop a discriminator (designated as an "amino-index") for the diagnosis of patients with advanced liver fibrosis. The area under the receiver operating characteristic curve (AUC) was used for evaluation of the diagnosis. RESULTS: (Phe)/(Val)+(Thr+Met+Orn)/(Pro+Gly) was derived as the optimal amino index. The AUCs were 0.92+/-0.04 (SE) and 0.99+/-0.01 for discriminating advanced fibrosis (fibrosis stages F3 and F4) and for discriminating cirrhosis, respectively. By use of the optimal cut-off values, both the sensitivity and specificity achieved a score over 0.88. CONCLUSION: Fibrosis index based on amino acid concentration could be applied to diagnose liver fibrosis as a convenient noninvasive approach.

Journal Article↗

Documented subacute stent thrombosis within thirty days after stenting with sirolimus-eluting stent (Cypher) for acute myocardial infarction: a Japanese single center retrospective non-randomized study.

BACKGROUND: The incidence of subacute stent thrombosis (SAT) within 30 days after stenting with a sirolimus-eluting stent (Cypher) for acute myocardial infarction (AMI) was retrospectively compared to that with bare-metal stents (BMS). METHODS AND RESULTS: Among 559 lesions in 558 consecutive AMI from April 2003 to February 2006, the incidence of documented SAT after Cypher implantation (2/276 lesions, 0.72%) was almost the same as for BMS (2 cases, 0.71%). Aspirin (81-100 mg/day) plus ticlopidine (200 mg/day) were administered continuously after admission in all 4 cases. CONCLUSION: Documented SAT did not increase after stenting with Cypher for AMI under aspirin plus ticlopidine.

Aged↗

Cross-bridge-dependent change in Ca2+ sensitivity is involved in the negative inotropic effect of nifedipine in aequorin-injected ferret ventricular muscles.

BACKGROUND: We hypothesized that the negative inotropic effect of nifedipine (Nif) on cardiac ventricular muscle is partly due to the cross-bridge-dependent decrease of Ca2+ sensitivity of the myofilaments as well as the decrease in Ca2+ influx. METHOD AND RESULTS: We used aequorin-injected ferret papillary muscles and measured the slope of the extra-Ca(2+)-tension relation which expresses the change in the Ca2+ sensitivity through the feedback from the cross-bridges. Twitch tension was decreased significantly by 0.5 micromol/L Nif accompanying a significant reduction of the Ca2+ transient peak. When Nif (0.2-0.5 micromol/L) was added to the solution with 8 mmol/L Ca2+, the slope of the extra-Ca2+-tension relation became steeper in a concentration-dependent manner, which was similar to the change in the slope when the concentration of Ca2+ was decreased from 8 to 1 mmol/L in the absence of Nif. BAY-K 8644 (0.3 micromol/L), a dihydropyridine receptor agonist, showed the opposite effect on the slope of the extra-Ca2+-tension relation to that observed in Nif. However, 2,3-butanedione monoxime (3 mmol/L), an inhibitor of the active cross-bridges, antagonized the effect of BAY-K 8644. CONCLUSION: Nif exerts its negative inotropic effect on cardiac muscle by suppressing Ca2+ binding to troponin C via the inhibition of the L-type Ca2+ channel, and by the cross-bridge-dependent decrease in the Ca2+ sensitivity, as in low extracellular Ca2+ concentration.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Cross-bridge-dependent change of the Ca2+ sensitivity during relaxation in aequorin-injected tetanized ferret papillary muscles.

UNLABELLED: BACKGROUND The aim of the present study was to indicate the cross-bridge-dependent change in the Ca2+ affinity of troponin-C (TnC) during relaxation in an intact preparation, because the intracellular mechanism of relaxation is not fully understood, although several methods of evaluating global diastolic function have been reported. METHODS AND RESULTS: The aequorin method was used with intact ferret papillary muscles and a tetanic contraction was induced by a repetitive electrical stimulation in the presence of ryanodine. The extra-Ca2+, the transient increase in the intracellular Ca2+ concentration in response to a rapid reduction in muscle length, which reflects the change in the Ca2+ affinity of TnC because of cross-bridge detachment, was measured, and the cross-bridge-dependent change in the Ca2+ affinity of TnC was estimated by observing the change in the slope of the extra-Ca2+ -tension relation. The extra-Ca2+ -tension relation measured during relaxation became steeper than that during contraction in all cases. The extra-Ca2+ -tension relation became steeper in the presence of 20 mmol/L caffeine during contraction in all cases. CONCLUSION: During relaxation, the downstream-dependent change in the Ca2+ affinity of TnC was enhanced, compared with that during contraction, because of a decrease in the number of attached cross-bridges.

Aequorin↗

Multiresolution phase retrieval in the fresnel region by use of wavelet transform.

A multiresolution (multiscale) analysis based on wavelet transform is applied to the problem of optical phase retrieval from the intensity measured in the in-line geometry (lens-free). The transport-of-intensity equation and the Fresnel diffraction integral are approximated in terms of a wavelet basis. A solution to the phase retrieval problem can be efficiently found in both cases using the multiresolution concept. Due to the hierarchical nature of wavelet spaces, wavelets are well suited to multiresolution methods that contain multigrid algorithms. Appropriate wavelet bases for the best solution approximation are discussed. The proposed approach reduces the computational complexity and accelerates the convergence of the solution. It is robust and reliable, and successful on both simulated and experimental images obtained with hard x rays.

Algorithms↗

Reconstruction of complex-valued electron density with x-ray in-line holograms.

A reconstruction algorithm is proposed to analyze the complex-valued electron-density distribution in an object with x-ray in-line holograms. The real and imaginary parts of the electron density correspond to local variations of x-ray phase shift and absorption, respectively. In the algorithm, the least-squares error of the holograms is iteratively minimized under sign constraints on the real and imaginary parts. The constraints, which are derived from the physical conditions in the interaction between x rays and materials, facilitate robust reconstruction. The reconstruction was applied to holograms of a biological specimen that caused both phase shift and absorption.

Journal Article↗

Facilitation of rotablator-stenting by measuring angiographic lesion length with the navicath (type-MUTO), a new measuring microcatheter.

In the present study, the usefulness and feasibility of a new measuring microcatheter, the Navicath (Type-MUTO) microcatheter, for facilitating the stenting procedure subsequent to ablation using a rotablator (rota-stenting) is described. A method for measuring the length of the targeted lesion (lesion length) angiographically with the Navicath when exchanging the guide wires is presented using 2 representative cases of rota-stenting. In addition, the validity of the selected stent according to the measurement of lesion length with the Navicath was evaluated by comparing the length of the selected stent with lesion length before PCI measured by quantitative coronary angiography. Based on the results obtained, we believe the Navicath is useful for facilitating rota-stenting, and may even be applicable to PCI in general.

Aged↗

Effectiveness of a sirolimus-eluting stent (Cypher) for diffuse in-stent restenosis inside a bare metal stent.

We estimated the benefit of a sirolimus-eluting stent (SES, Cypher) for diffuse (> 10 mm) in-stent restenosis (ISR) inside bare metal stents (BMS) because the feasibility of the SES was not confirmed after its recent approval in Japan. Clinical and angiographic outcomes after SES implantation to 93 diffuse ISR were compared with those of 3 groups treated by plain old balloon angioplasty (POBA, (n = 54)), cutting balloon angioplasty (CB, (n = 24)), and BMS (n = 41) in a series of 153 patients whose follow-up quantitative coronary angiography (QCA) evaluated 3-9 months after the treatments was obtained from January 2003 through December 2005. For 33 lesions in the SES group, 12-month follow-up QCA results were obtained and compared with those at 6 months. Ticlopidine (200 mg/day) was prescribed for at least 12 weeks after SES implantation and for 2 weeks after BMS in addition to aspirin (81-100 mg/day). Patient characteristics and the characteristics of previous implanted BMS in the SES group were not significantly different from those in the other groups. Death from cardiac causes and nonfatal myocardial infarction did not occur in any group. Stent thrombosis was not observed in the BMS and SES groups. The incidence of repeat target lesion revascularization (re-TLR) in the SES group (3.23%) was significantly lower compared with that of the POBA (37.0%), CB (25.0%), and BMS (29.3%) groups (P < 0.001, respectively). Late loss in the SES group (0.44 +/- 0.41 mm) was significantly smaller than that in the BMS group (1.34 +/- 0.74 mm) (P < 0.05). The rate of recurrent ISR (re-ISR) in SES (5.38%) was significantly lower than that in POBA (46.3%), CB (41.7%), and BMS (46.3%) (P < 0.001, respectively). The QCA variables at 6 months in the SES group were not significantly different from those at 12 months. Thus, SES implantation for diffuse ISR was far superior since it markedly reduced the incidence of re-TLR with re-ISR at up to 6-months follow-up. In addition, this angiographic patency after SES implantation continued until 12 months.

Angioplasty, Balloon, Coronary↗

First application of X-ray refraction-based computed tomography to a biomedical object.

We have developed X-ray refraction-based computed tomography (CT) that is able to visualize soft tissue in between hard tissue. The experimental system consists of Si(220) diffraction double-crystals and is called the DEI (diffraction-enhanced imaging) method, in which the object is located between the crystals and a CCD camera to acquire data as 360 X-ray images. The X-ray energy used was 17.5 keV. The algorithm used to reconstruct CT images was developed by A. Maksimenko and colleagues. We successfully visualized articular cartilage and the distribution of bone marrow, which are inner structures. Our method has much higher contrast compared to the conventional absorption-based CT system.

Algorithms↗