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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 19 recordsLinked to original sources
PubMed2007

Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to S-1/cisplatin in gastric cancer.

High expression of thymidylate synthase (TS) and inactivation of p53 are allegedly associated with chemoresistance. The authors evaluated TS and p53 expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy. Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric cancers were immunostained for TS and p53 protein after appropriate antigen retrieval. Fifty-one cases without neoadjuvant chemotherapy were also studied. In the pretreatment biopsies, high expression of TS was seen in 8% of the histologic responders, in 28% of the nonresponders and in 31% of the controls. High expression of p53 was observed in 56% of the nonresponders, but in 8% of the responders and in 29% of the controls (P<0.01 and P<0.05, respectively). The TS- and/or p53-high phenotype was seen in 76% of the nonresponders and in 54% of the controls, but in 8% of the responders (P<0.0001 and P<0.005, respectively). The data of the surgical specimens were consistent with those of the pretreatment biopsies. These results suggest that immunostaining for TS and p53 protein is useful for pretreatment selection of gastric cancer patients unresponsive to S-1/cisplatin chemotherapy.

Antineoplastic Agents↗
PubMed2006

Compton scattering study of water versus ice Ih: intra- and intermolecular structure.

The hydrogen-bond geometries in water and polycrystalline ice Ih are studied using synchrotron radiation-based Compton scattering data of unprecedented statistical accuracy and consistency. By combining the experimental data with model calculations utilizing density functional theory, we show that the technique provides unique and complementary information on hydrogen bonding in water. The comparison of water and ice indicates the necessity of including a local intra-intermolecular geometric correlation for water, relating the intramolecular O-H bond length to the corresponding hydrogen-bond geometry. By using the hydrogen-bond geometries obeying this correlation, we demonstrate a further constraint on the angular distortions of the hydrogen bonds in water.

Journal Article↗
PubMed2006

The usefulness of a continuous administration of tirapazamine combined with reduced dose-rate irradiation using {gamma}-rays or reactor thermal neutrons.

We clarified the usefulness of the continuous administration of tirapazamine (TPZ) in combination with reduced dose-rate irradiation (RDRI) using gamma-rays or reactor thermal neutrons. Squamous cell carcinoma (SCC) VII tumour-bearing mice received a continuous administration of 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells. Then, they received a single intraperitoneal injection or 24 h continuous subcutaneous infusion of TPZ in combination with conventional dose-rate irradiation (CDRI) or RDRI using gamma-rays or thermal neutrons. After irradiation, the tumour cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total tumour cells was determined using tumours that were not pre-treated with BrdU. The sensitivity of both total and Q cells, especially of Q cells, was significantly reduced with RDRI compared with CDRI. Combination of TPZ increased the sensitivity of both populations, with a slightly more remarkable increase in Q cells. Furthermore, the continuous administration of TPZ raised the sensitivity of both total and Q cell populations, especially the former, more markedly than the single administration, whether combined with CDRI or RDRI using gamma-rays or thermal neutrons. From the viewpoint of solid tumour control as a whole, including intratumour Q-cell control, the use of TPZ, especially when administered continuously, combined with RDRI, is useful for suppressing the reduction in the sensitivity of tumour cells caused by the decrease in irradiation dose rate in vivo.

Animals↗
PubMed2006

Observation of a strongly nested Fermi surface in the shape-memory alloy Ni0.62Al0.38.

The Fermi surface topology of the shape-memory alloy Ni0.62Al0.38 has been determined using Compton scattering. A large area of this Fermi surface can be made to nest with other areas by translation through a vector of approximately 0.18[1,1,0](2pi/a), which corresponds to the wave vector associated with martensitic precursor phenomena such as phonon softening and diffuse streaking in electron diffraction patterns. This observation is compelling evidence that these phenomena are driven by the enhanced electron-lattice coupling due to the Fermi surface nesting.

Journal Article↗
PubMed2006

The measurement of low levels of factor VIII or factor IX in hemophilia A and hemophilia B plasma by clot waveform analysis and thrombin generation assay.

BACKGROUND: Precise assessment of clotting function is essential for monitoring of hemostatic treatment for hemophilias A and B. MATERIALS AND METHODS: Clot waveform analysis and thrombin generation assays were performed on factor (F) VIII- and FIX-deficient plasmas, which had been reconstituted with known amounts of recombinant FVIII (rFVIII) and affinity-purified FIX respectively. Clot waveforms were assessed qualitatively and quantitatively by measuring the parameters clotting time, maximum coagulation velocity (Min1), and maximum coagulation acceleration (Min2). The thrombin generation assay was also assessed qualitatively and measurements made of time to peak and peak height. RESULTS: Overall results obtained with both assays showed good correlation for both clotting factors confirming that the changes in clotting waveform reflected changes in thrombin generation. Both assays demonstrated a predictable dose response to the addition of FVIII or IX. However, clot waveform analysis was more sensitive than the thrombin generation assay, particularly in detecting very low levels (0-0.1 IU dL(-1)) of both factors. CONCLUSIONS: These data suggest that the application of clot waveform analysis to the routine management of the hemophiliacs could increase our understanding of the clinical significance of low levels of FVIII and FIX that cannot be measured by assays in current use. This may be particularly useful in the management of hemophiliacs with inhibitors or undergoing gene therapy.

Biometry↗
PubMed2006

Factor V C2 domain contains a major thrombin-binding site responsible for thrombin-catalyzed factor V activation.

Factor (F)V is converted into its active form, FVa, by limited proteolysis. Thrombin-catalyzed activation of FV is essential for its full cofactor activation. Previously, we reported that thrombin was bound to the C2 domain in the light chain of FVIII. As FV has a similar domain structure to FVIII, we focused on the FV C2 domain as a possible binding region for thrombin. Kinetic parameters, measured by surface plasmon resonance, revealed that the K(d) values of anhydro-thrombin for FV, FVa, and the FV C2 domain were 66, 240, and 670 nmol L(-1), respectively. FV activation was increased by approximately 9-fold by the addition of thrombin. In the presence of the FV C2 domain, this increase of the FV activation was inhibited. However, FV activation was not inhibited by the addition of the FVIII C2 domain. FV was cleaved into a 105-kDa heavy chain and a 71/74-kDa light chain by thrombin-catalyzed proteolysis at Arg709, Arg1018 and Arg1545. In the presence of the FV C2 domain, the cleavage was inhibited at all sites. Proteolysis was not affected by the addition of the FVIII C2 domain. These results indicated that the FV C2 domain contains a major binding site for thrombin and that this domain is necessary for the proteolysis at all cleavage sites. Furthermore, the present results also suggested that thrombin has an independent binding site for FV different from that for FVIII.

Binding, Competitive↗
PubMed2006

Characteristics of sediments in a newly constructed reservoir in Japan.

The sediment formation mechanisms of a newly constructed reservoir in Ehime, Japan were evaluated by characterizing the soil particles (SP) and particulate phosphorus (PP) in the runoff and reservoir sediments. The SP and PP loads from the runoffs of the main river in the watershed considerably increased, when the specific discharge rates were over 300 l/s/km2 (high flow conditions). When the specific discharge rates exceeded over 300 l/s/km2, 19% of the watershed generated over 80% of the SP and PP loads. When the specific discharge rates were under 300 l/s/km2 (low flow conditions), the contributions of the previously mentioned 19% area to the SP and PP loads were smaller. Significant amounts of smectite were found in the sediments in the reservoir and in the soil samples obtained at the forest exposed area in this 19% area while it was negligible in citrus orchards and paddy fields that constituted the remaining land surfaces. The forest area exposed by recent landslides was significant for the SP and PP in the reservoir. Judging from the outcomes, land use information alone may not be sufficient to detect critical sources of SP and PP in the runoffs and reservoirs. To identify and confirm crucial areas for the SP and PP in the runoffs, the investigations should be conducted under high flow conditions and the composition of clay minerals in the sediments should be checked against the clay mineral distributions of soils in the watershed.

Conservation of Natural Resources↗
PubMed2005

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

Animals↗
PubMed2005

Treatment of unruptured cerebral aneurysms; a multi-center study at Japanese national hospitals.

The treatment and natural course of unruptured cerebral aneurysms were analyzed in 615 patients with 712 unruptured cerebral aneurysms registered from seven Japanese national hospitals and Zurich University hospital. For 209 aneurysms in 181 cases, the natural course of the aneurysms was observed without surgical treatment. During the follow-up period of 3,862 months (321.8 years), 11 of these aneurysms ruptured giving a rupture rate of 3.42%/year. Five of these 11 aneurysms were less than 10 mm in diameter. Seventeen aneurysms of these 209 untreated aneurysms had blebs. Seven of these 17 aneurysms ruptured yielding the high rupture rate of 28.3%/year. The likelihood of unruptured cerebral aneurysms to rupture was not exceedingly low even when the aneurysms were smaller than 10 mm. Since the risk of rupture and morbidity in relation to surgical treatment cannot be predicted by size alone, the morphology, especially the presence of blebs, should be considered when treating unruptured cerebral aneurysms. In 434 patients, 503 cerebral aneurysms were treated surgically either by craniotomy in 472 aneurysms or endovascular coil embolization in 31 aneurysms. Surgical outcome was influenced by the presence of concurrent diseases, patient age, size and location of the aneurysms. Complications after surgical treatment of 128 incidentally found aneurysms were reported in four cases; three cases of hemiparesis and one case showing disturbance of higher brain function, with a morbidity rate of 3.1%. These results suggest that surgical treatment may be acceptable in cases of incidentally found cerebral aneurysms, especially when blebs are present.

Adult↗
PubMed2005

Real-time and automatic sorting of multi-neuronal activity for sub-millisecond interactions in vivo.

Recent in vitro electrophysiological studies have revealed that neighboring interneurons interact with each other in a sub-millisecond time range via gap junctions and that individual dendritic compartments generate local excitation spikes and back-propagated spikes within a single-neuron. However, most in vivo electrophysiological studies using behaving animals only focus on activity rates of single-neurons and/or large neuronal populations without considering the potential role of such sub-millisecond interactions among neurons. This neglect is due to the limitation of ordinary in vivo multi-neuronal recording and spike sorting techniques applied to behaving animals. Though independent component analysis (ICA) is a powerful method to overcome certain limitations, ICA has a serious problem in that the number of single-electrodes (microwires) must be more than the number of single-neurons to be recorded. Our recently-developed method has solved this limitation of ICA, but a few problems have remained: the computational load is heavy, the method can be used only for off-line, not real-time, processing, and the electrode-neuron drift problem remains unsolved. In this paper, solving all these problems, we introduce a novel system consisting of automatic and real-time spike sorting with ICA in combination with a newly developed multi-electrode, dodecatrode. The system has the potential to answer some important neurobiological questions that have not been explored in in vivo electrophysiological experiments: how sub-millisecond interactions between closely neighboring single-neurons act in freely behaving animals. The system promises to be a bridge connecting electrophysiological studies in vitro and in vivo.

Action Potentials↗
PubMed2005

7-12 Hz cortical oscillations: behavioral context and dynamics of prefrontal neuronal ensembles.

7-12 Hz Oscillations, characterized by spindle-like high-voltage rhythmic spike components, appear in quiet immobile states of rats. However, it remains unclear what their relationships with preceding behavioral activities are and how prefrontal neuronal dynamics during these oscillations is. In the present study, we first determined the relationship of 7-12 Hz oscillations with the wake-sleep cycle and preceding behavioral activities in several normal rat strains by recording electroencephalograms from the multiple cortical regions. Prolonged awake period transiently enhanced the following appearance of 7-12 Hz oscillations, which were frequently followed by slow-wave sleep. The degree of transient enhancement under the task condition was similar to that by prolonged wakefulness under the no-task condition. In addition, by recording local-field potential and multi-unit activities in the medial prefrontal cortex, we determined the temporal dynamics of prefrontal neuronal activities in relation to 7-12 Hz oscillations. Collective neuronal activities in medial prefrontal cortex were gradually organized into phase-locked patterns and showed highly synchronization during these oscillations. These dynamics were in temporal proximity to those of slow-wave activities (<4 Hz). Since slow-wave activities are thought to synchronize large spatial domains, these results suggest that 7-12 Hz oscillations are involved in the transition from the awake to sleep states by oscillatory entrainment of global cortical networks including the prefrontal neurons.

Action Potentials↗
PubMed2005

Optimization of aromatic side chain size complementarity in the hydrophobic core of a designed coiled-coil.

The coiled-coil structure plays an important roles, especially in protein assembly. Previously we constructed AAB-type heterotrimeric coiled-coils by manipulating the packing in the hydrophobic core using Trp and Ala residues, where one Trp and two Ala residues were placed in the hydrophobic core instead of three Ile residues. To optimize the packing complementarity in the hydrophobic core, we investigated the effects of introducing various aromatic amino acids on the formation of an AAB-type heterotrimeric coiled-coil, by circular dichroism, thermal stability, and nuclear magnetic resonance (NMR) studies. We found that the Phe residue was more suitable for heterotrimeric coiled-coil formation than the Trp residue, when combined with two Ala residues, whereas the Tyr and His residues did not induce the coiled-coil structure efficiently.

Amino Acid Sequence↗
PubMed2005

Combination of boron and gadolinium compounds for neutron capture therapy. An in vitro study.

In neutron capture therapy, the therapeutic effect of the boron compound is based on alpha particles produced by the B(n, alpha) reaction while with the gadolinium compound the main radiation effect is from gamma rays derived from the Gd(n, gamma) reaction. The uptake and distribution within the tumor may be different among these compounds. Thus, the combination of the boron and gadolinium compounds may be beneficial for enhancing the radiation dose to the tumor. Chinese hamster fibroblast V79 cells were used. For the neutron targeting compounds, 10B (BSH) at 0, 5, 10, and 15 ppm, and 157Gd (Gd-BOPTA) at 0, 800, 1600, 2400, 3200, and 4800 ppm, were combined. The neutron irradiation was performed with thermal neutrons for 30 min. (neutron flux: 0.84 x 10(8) n/cm2/s in free air). The combination of the boron and gadolinium compounds showed an additive effect when the gadolinium concentration was lower than 1600 ppm. This additive effect decreased as a function of gadolinium concentration at 2400 ppm and resulted in no additive effect at more than 3200 ppm of gadolinium. In conclusion, the combination of the boron and gadolinium compounds can enhance the therapeutic effect with an optimum concentration ratio. When the gadolinium concentration is too high, it may weaken the boron neutron capture reaction due to the high cross-section of gadolinium compound against neutrons.

Animals↗
PubMed2004

The usefulness of 2-nitroimidazole-sodium borocaptate-10B conjugates as 10B-carriers in boron neutron capture therapy.

We evaluated the usefulness of five new (10)B-compounds (TX-2016, TX-2017, TX-2018, TX-2041, and TX-2042) as (10)B-carriers in boron neutron capture therapy (BNCT). They are 2-nitroimidazole-sodium borocaptate-(10)B (BSH) conjugates, that is, hybrid compounds that have both hypoxic tumor cell sensitizing unit under gamma-ray irradiation, 2-nitroimidazoles, and thermal neutron-sensitizing unit, BSH. (10)B distribution analyses in tumors and blood indicated that TX-2041 has the most favorable characteristics for localizing a sufficient amount of (10)B into tumors and keeping the (10)B concentration high during neutron beam irradiation. In addition, TX-2041 showed a significantly higher radio-sensitization effect with reactor thermal neutron beams than BSH on both total (=proliferating (P) + quiescent (Q)) and hypoxia-rich Q cell populations in solid tumors. Further, TX-2041 clearly demonstrated a radio-sensitization effect with gamma-rays on both cell populations, which could never be achieved by BSH. (10)B-carriers with a hypoxic tumor cell-sensitizing effect on tumors with gamma-rays as well as the potential to selectively localize and keep (10)B in tumors, such as TX-2041, are promising for use in actual BNCT.

Animals↗
PubMed2004

The irradiation system and dose estimation joint-system for NCT wider application in Kyoto University.

The research for neutron capture therapy (NCT) at the Kyoto University Research Reactor (KUR) has been remarkably developing after December 2001. However, the most important subject is the preparations for the KUR provisional shutdown coming in March 2006. In this paper, our present concept and plan are reported about the novel irradiation system and dose estimation system for wider applications of NCT. For the irradiation field, the target nuclear reaction was selected to (7)Li(p,n)(7)Be and the neutron moderator was selected to heavy water. The minimum proton current was about 13 mA for epi-thermal neutron irradiation, and about 9 mA for mix-neutron irradiation. In thermal neutron irradiation, the proton current needed more than 18 mA for 2.5-MeV protons, but only 4 mA for 5.0-MeV protons. For the dose estimation system, we are aiming at the completion of the "dose estimation joint-system". The data from the on-line measurement systems such as beam monitors and gamma-ray telescopes are fed back to the results for the in-body dose estimation, and then the dose estimations for irradiation field and a living body are jointed. For the beam-monitor system, multi-chamber method was adopted. The surveys were performed for the wall materials and chamber gases.

Boron Neutron Capture Therapy↗
PubMed2004

Development of real-time thermal neutron monitor using boron-loaded plastic scintillator with optical fiber for boron neutron capture therapy.

A new thermal neutron monitor for boron neutron capture therapy was developed in this study. We called this monitor equipped boron-loaded plastic scintillator that uses optical fiber for signal transmission as an [scintillator with optical fiber] SOF detector. A water phantom experiment was performed to verify how the SOF detector compared with conventional method of measuring thermal neutron fluence. Measurements with a single SOF detector yielded indistinguishable signals for thermal neutrons and gamma rays. To account for the gamma ray contribution in the signal recorded by the SOF detector, a paired SOF detector system was employed. This was composed of an SOF detector with boron-loaded scintillator and an SOF detector with a boron-free scintillator. The difference between the recorded counts of these paired SOF detectors was used as the measure of the gamma ray contribution in the measured neutron fluence. The paired SOF detectors were ascertained to be effective in measuring thermal neutron flux in the range above 10(6)(n/cm(2)/s). Clinical trials using paired SOF to measure thermal neutron flux during therapy confirmed that paired SOF detectors were effective as a real-time thermal neutron flux monitor.

Boron Neutron Capture Therapy↗