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Biomedical subjects

Takuya Hashimoto

Publications and source records attributed to Takuya Hashimoto.

17 recordsLinked to original sources

Enantioselective 1,3-dipolar cycloaddition reaction between diazoacetates and alpha-substituted acroleins: total synthesis of manzacidin A.

A titanium BINOLate catalyzed asymmetric 1,3-dipolar cycloaddition reaction between alpha-substituted acroleins and alkyl diazoacetates has been developed. With this methodology in hand, chiral 2-pyrazolines containing a quaternary stereogenic center were obtained in high to excellent enantioselectivities (up to 95% ee). The synthetic utility of the optically enriched 2-pyrazoline thus obtained was demonstrated in the short synthesis of manzacidin A.

Acetates↗

Estimation of standard liver volume in Japanese living liver donors.

BACKGROUND: Standard liver volume (SLV) is an important concept in adult living liver donor transplantation. The purpose of this study was to re-evaluate and modify the authors' previous formula for predicting total liver volume (TLV). METHODS: The TLV of 301 Japanese living donors was measured by computed tomography. This TLV was then compared with the liver volume calculated using established formulas. The correlation between TLV and several factors including body surface area (BSA) were analyzed and a new equation (SLVn) to better approximate TLV was determined. Factors related to the difference between TLV and SLVn were examined. RESULTS: Average TLV was 1196.3 +/- 221.0 cm3. Urata's formula underestimated TLV by 17.6 cm3 and the other formulas overestimated it by 120.4-244.9 cm3. TLV could be approximated by BSA; SLVn (cm3) = -404.8 + 961.3 x BSA (m2, R2 = 0.58). SLVn tended to overestimate the TLV of older donors and to underestimate TLV of thin donors. CONCLUSIONS: A new simple formula is presented that might be a better fit for calculating TLV in Japanese adults. This formula might be useful for evaluating the size of an adequate graft.

Adolescent↗

Asymmetric 1,3-dipolar cycloaddition reaction of nitrones and acrolein with a bis-titanium catalyst as chiral Lewis acid.

A mu-oxo-type chiral bis-Ti(IV) oxide (S,S)-1 can be successfully utilized in the asymmetric 1,3-dipolar cycloaddition reactions between various nitrones 2 and acrolein to give the corresponding isoxazolidines with high to excellent enantioselectivities. For instance, the reaction between nitrone 2 (R = t-Bu) and acrolein in the presence of 10 mol % of bis-Ti(IV) catalyst (S,S)-1 in dichloromethane at -40 degrees C gave the corresponding endo cycloadduct with 97% ee.

Journal Article↗

Superior vena cava graft for right liver and right lateral sector transplantation.

BACKGROUND: The usefulness of cryopreserved superior vena cava (SVC) grafts for venous reconstruction remains to be evaluated in right liver and right lateral sector transplantation. METHODS: Reconstruction of the hepatic vein was performed when the congested area in the liver graft was significant. A vein graft with a suitable shape and length meeting the demands for the venoplasty was selected, and SVC grafts were used in 20 recipients. Surgical techniques were classified into five types according to the necessity of middle or short hepatic vein reconstruction in the liver graft. Surgical outcomes and vein graft patency were evaluated. RESULTS: All 20 recipients survived the operation without any complications caused by congestion. Liver functions were well recovered in the early postoperative period. The 1-year primary patency rates of cryopreserved vein grafts used for reconstructed right hepatic veins, inferior right hepatic veins, and middle hepatic vein tributaries were 100%, 94%, and 42%, respectively. CONCLUSIONS: SVC grafts were feasible for outflow tract reconstruction in right liver and right lateral sector transplantation, although the long-term patency of the grafts for middle hepatic vein reconstruction remains to be evaluated.

Aspartate Aminotransferases↗

Reconstruction of the middle hepatic vein tributary in a right lateral sector graft.

A right lateral sector graft (RLSG) was devised to overcome graft-size disparity in living donor liver transplantation (LDLT). When the RLSG has a middle hepatic vein (MHV) tributary, which drains a significant part of segment VI, the MHV tributary (V6) should be reconstructed to avoid congestion of the RLSG. In the donor operation, congestive area of segment VI was identified by 5 minutes of simultaneous clamping of V6 and the hepatic artery to the right lateral sector. An RLSG was harvested, preserving the V6 orifice. After plastic surgery of outflow veins including V6 using venous grafts, the RLSG was implanted into the recipient. In 19 patients who received RLSG in our institution, 2 RLSGs required V6 reconstruction. The postoperative courses of these two recipients and donors were uneventful. In conclusion, the present technique might be useful to avoid complications due to congestion and poor function of the relevant graft area and might help to expand the indications for RLSG.

Adult↗

New hepatic vein reconstruction in left liver graft.

The incidence of hepatic venous stenosis is higher in partial liver transplantation. New methods for hepatic venous reconstruction in left liver transplantation, which secure wide anastomosis, were devised and are reported here. In the graft, the right side of the middle hepatic vein or the left side of the left hepatic vein was cut longitudinally and a rectangular-shaped vein patch was attached for venoplasty. In the recipient, after the left and middle hepatic veins were joined, the right side of the middle hepatic vein was cut toward the closed right hepatic vein, making a horizontal cavotomy for anastomosis. Of 92 patients who underwent conventional hepatic vein reconstruction, 3 were complicated by hepatic venous stenosis (median follow-up 43 months). By contrast, there were no hepatic vein complications in the 20 patients who underwent the new technique (7 months). The current method appears to be technically feasible for outflow reconstruction in left liver graft transplantation.

Adult↗

Bilioenteric reconstruction for small bile ducts without mucosa-to-mucosa alignment: long-term results.

HYPOTHESIS: Biliary reconstruction of the small bile duct is difficult, and bilioenteric reconstruction without mucosa-to-mucosa alignment would be a simple and useful maneuver in this situation; however, the long-term results of this surgical technique remain to be evaluated. OBJECTIVE: To evaluate the usefulness of bilioenteric reconstruction without mucosa-to-mucosa alignment from the standpoint of the long-term results. DESIGN: Retrospective review. SETTING: University hospital. PATIENTS: Bilioenteric reconstruction without mucosa-to-mucosa alignment was performed in 17 patients at our institution. Six patients had malignancy, and 11 were liver transplant recipients from a living donor. MAIN OUTCOME MEASURES: Clinical records, blood chemistry data, and findings from dynamic computed tomography. RESULTS: Among the 17 patients, 4 died of recurrent malignant disease, and 3 died of thrombosis, brain hemorrhage, and pneumonia, respectively. During the follow-up (median, 41.2 months) of the remaining 10 patients, cholangitis occurred in 2 (1 episode in each), and anastomotic leakage from the hepaticojejunostomy performed by the standard method for other thicker ducts developed in 1. There were no other anastomosis-related complications. Dynamic computed tomography performed 2.4 to 62.7 months (median, 34.4 months) after the operation showed no bile duct dilatation in any of the 10 cases. CONCLUSIONS: Long-term patency of the small bile ducts after bilioenteric reconstruction without mucosa-to-mucosa alignment was demonstrated. Thus, this technique is useful for the reconstruction of small bile ducts, especially in patients with poor liver function in whom even minimal additional reduction in the volume of functioning liver due to occlusion of a small bile duct would be acceptable.

Adolescent↗

Development of an electro-stethoscope system and design of an optimum filter based on tissue sound transmission for noninvasive early diagnosis of malfunction of an implanted mechanical total artificial heart.

Early diagnosis of the malfunction of a mechanical artificial heart implanted in a patient who has been discharged from hospital is very important. We have developed an electro-stethoscope system that enables the malfunction of an artificial heart to be detected from the analysis of sound signals from the artificial heart. The sound data can be transmitted to a hospital via a mobile telephone or the Internet, so that doctors can examine the condition of the artificial heart. The optimum frequency characteristics of a low-pass filter for the elimination of ambient sound through the electro-stethoscope casing were obtained by simulating sound transmission through tissue. We evaluated the usefulness of the electro-stethoscope system using a goat in which an undulation pump total artificial heart had been implanted. A frequency analysis of the sound signal provided information on the degree of degradation of each mechanical component of the artificial heart. The results of this study showed that the electro-stethoscope system is useful for the early detection of the malfunction of an artificial heart at home, and that the use of the system contributes to improvement in the quality of life of patients.

Animals↗

Catalytic asymmetric allylation of aldehydes and related reactions with bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as a mu-oxo-type chiral Lewis acid.

A new, chiral bis-Ti(IV) oxide of type 3 has been designed and can be utilized for strong activation of aldehyde carbonyls, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin. The chiral bis-Ti(IV) catalyst (S,S)-3 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide with (S)-BINOL or by treatment of ((S)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. Treatment of hydrocinnamaldehyde with allyltributyltin under the influence of chiral bis-Ti(IV) oxide (S,S)-3 generated in situ (10 mol %) in CH(2)Cl(2) afforded an allylation product in 84 % yield and with 99 % ee. This asymmetric allylation with non-racemic bis-Ti(IV) oxide 3 and partially resolved (S)-BINOL shows a positive nonlinear effect in correlation of the enantiopurity of the allylation product with the ee of the (S)-BINOL. Chiral bis-Ti(IV) oxide (S,S)-3 can also be utilized for related reactions such as asymmetric methallylation and propargylation of aldehydes with high enantioselectivity. This asymmetric approach provides a very useful way of obtaining high reactivity and selectivity through the simple introduction of the M-O-M unit into the design of chiral Lewis acid catalysts.

Journal Article↗

Bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as a mu-oxo-type chiral Lewis acid: application to catalytic asymmetric allylation of aldehydes.

A new, chiral bis-Ti(IV) oxide of type 1 was successfully designed and can be utilized for strong activation of aldehyde carbonyls, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin. The chiral bis-Ti(IV) catalyst (S,S)-1 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide with (S)-binaphthol or by reaction of ((S)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. Reaction of hydrocinnamaldehyde with allyltributyltin (1.1 equiv) under the influence of in situ generated chiral bis-Ti(IV) oxide (S,S)-1 (10 mol %) in CH2Cl2 at 0 degrees C for 4 h afforded 1-phenyl-5-hexen-3-ol in 84% yield with 99% ee. The present asymmetric allylation using nonracemic bis-Ti(IV) oxide 1 with partially resolved (S)-binaphthol exhibits a positive nonlinear effect in correlating the enantiopurity of allylation product with the ee of (S)-binaphthol. This asymmetric approach provides a very useful way for obtaining high reactivity and selectivity by the simple introduction of the M-O-M unit in the design of chiral Lewis acid catalysts.

Journal Article↗

Design of a miniature implantable left ventricular assist device using CAD/CAM technology.

In this study, we developed a new miniature motor-driven pulsatile left ventricular assist device (LVAD) for implantation into a Japanese patient of average build by means of computer-aided design and manufacturing (CAD/CAM) technology. A specially designed miniature ball-screw and a high-performance brushless DC motor were used in an artificial heart actuator to allow miniaturization. A blood pump chamber (stroke volume 55 ml) and an inflow and outflow port were designed by computational fluid dynamics (CFD) analysis. The geometry of the blood pump was evaluated using the value of index of pump geometry (IPG) = (Reynolds shear stress) x (occupied volume) as a quantitative index for optimization. The calculated value of IPG varied from 20.6 Nm to 49.1 Nm, depending on small variations in pump geometry. We determined the optimum pump geometry based on the results of quantitative evaluation using IPG and qualitative evaluation using the flow velocity distribution with blood flow tracking. The geometry of the blood pump that gave lower shear stress had more optimum spiral flow around the diaphragm-housing (D-H) junction. The volume and weight of the new LVAD, made of epoxy resin, is 309 ml and 378 g, but further miniaturization will be possible by improving the geometry of both the blood pump and the back casing. Our results show that our new design method for an implantable LVAD using CAD/CAM promises to improve blood compatibility with greater miniaturization.

Computer-Aided Design↗

Blood compatible design of a pulsatile blood pump using computational fluid dynamics and computer-aided design and manufacturing technology.

Thrombus formation is a critical issue when designing a long-term implantable left ventricular assist system (LVAS). Fluid dynamic characteristics of blood flow are one of the main factors that cause thrombus formation. In this study, we optimized the fluid dynamics of a sac blood pump in our LVAS to ensure minimization of shear-related blood damage that could lead to thrombus formation. A pump housing and a sac chamber were designed with computer-aided design (CAD) software, and fluid dynamics were estimated by computational fluid dynamic (CFD) analysis. We adopted distribution of CFD results for qualitative evaluation, and we also tried to estimate normalized index of hemolysis (NIH) from the results of CFD analysis as a quantitative index of optimization for geometry of the blood pump chamber. A prototype model of the optimized blood pump was made using a three-axis computer machine tool by whittling pieces of nonfoamed polyurethane. Shear stress and theoretical NIH in the redesigned model were lower than those in the first model. Area of flow stagnation that was observed in the first model was not seen in the redesigned model. The results demonstrate that application of CAD/CAM technology to design an artificial heart contributes to optimizing a blood pump chamber for the purpose of reducing thrombus formation.

Biomedical Technology↗

Refinement of crystal structural parameters and charge density using convergent-beam electron diffraction--the rhombohedral phase of LaCrO3.

Atom positions and anisotropic Debye-Waller factors of the rhombohedral phase of LaCrO(3) have been refined simultaneously with the low-order structure factors, using a structure-analysis method of convergent-beam electron diffraction (CBED) proposed by Tsuda & Tanaka [Acta Cryst. (1999), A55, 939-954]. The method is based on the least-squares fitting between full dynamical calculations and energy-filtered intensities of two-dimensional higher-order Laue-zone (HOLZ) and zeroth-order Laue-zone (ZOLZ) CBED patterns. The positions of the oxygen atoms have been determined with a high precision. Clear anisotropy of the thermal vibrations of the oxygen atoms has been successfully determined by the CBED method for the first time. The charge transfer from the La and Cr atoms to the O atoms has been found from the deformation charge-density map.

Journal Article↗

Artificial chaperone-assisted refolding of bovine carbonic anhydrase using molecular assemblies of stimuli-responsive polymers.

An artificial chaperone, which can decrease the protein aggregation and increase the reactivation yield of denatured protein in a fashion similar to natural chaperone, was newly developed using stimuli-responsive polymers. It has previously been reported that the addition of poly(propylene oxide)-phenyl-poly(ethylene glycol) (PPOn-Ph-PEG) with the unit number of PPO (n) 33 could enhance the refolding of bovine carbonic anhydrase (Kuboi et al. J. Chromatogr. B 2000, 243, 213). PPO-Ph-PEG with a large PPO chain (n = 50) was synthesized and the surface properties were characterized by both the relative fluorescence intensity of 1-anilino-8-naphthalene sulfonate (ANS) and the fluidity determined by diphenylhexatriene (DPH). The variation of ANS intensity and DPH fluidity is shown in a diagram as functions of temperature and polymer concentration. The high values of ANS intensity and fluidity of PPO50-Ph-PEG were obtained in a relatively wide conditional range (more than 0.08 mM and more than 15 degrees C) although the conditions showing the high values of PPO33-Ph-PEG were restricted (more than 0.1 mM and more than 40 degrees C). It was also found that molecular assemblies of PPOn-Ph-PEG with diameters of 7-18 nm were formed in the above conditions. On the basis of the surface properties of their polymer self-assemblies, the possibility of using them as an artificial chaperone was investigated. The effect of the addition of PPOn-Ph-PEG on the reactivation yield of a model protein, carbonic anhydrase from bovine (CAB), and the optical density of the solution was examined at various temperatures and concentrations. The reactivation yield of CAB was strongly enhanced and the aggregate formation (the optical density) was suppressed by adding PPOn-Ph-PEG in the above conditions, which show high ANS intensity and DPH fluidity. Especially in the presence of 0.1 mM PPO50-Ph-PEG, the reactivation yield of CAB reached approximately 100% at 40-55 degrees C. It was thus found that self-assemblies of the present polymer could be utilized as an artificial chaperone by selecting suitable stimuli conditions.

Animals↗

Optimum selection of an implantable secondary battery for an artificial heart by examination of the cycle life test.

An implantable secondary battery is one of the key components in a total artificial heart system. Because a 2 year cycle life is required, the cycle life of the secondary battery as well as its charge and discharge properties are important parameters for selection of an appropriate battery. We carried out cycle life tests on four kinds of rechargeable batteries (a Ni-MH secondary battery, a Ni-Cd secondary battery, a Li-ion battery with a graphite anode, and a Li-ion battery with a nongraphitizable carbon electrode) to determine their suitability as implanted back-up batteries. Each of the batteries was charge/discharge cycled at 37 degrees C to 39 degrees C using a charge current of 1 C ampere, and they were each fully discharged under either pulsatile discharge loads, which mimicked pulsatile operation, or a nonpulsatile load equivalent to the average of the pulsatile loads. The two Li-ion batteries made by different manufacturers both met the minimum requirement of cycle life of more than 1,500 cycles, considering safety coefficient regardless of the discharge pattern. In addition, the temperature increase of these Li-ion batteries (3 degrees C) was lower than that of Ni-Cd and Ni-MH batteries (15-25 degrees C). Out of these four batteries, the two Li-ion batteries are the most suitable for use in a totally implantable artificial heart system.

Cadmium↗