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Biomedical subjects

Takashi Yamane

Publications and source records attributed to Takashi Yamane.

At least 19 recordsLinked to original sources

The pivot wash in two impeller modes for the Baylor/Miwatec centrifugal blood pump.

A centrifugal blood pump with a double pivot impeller and an eccentric inlet port is being developed as an implantable artificial heart by the Baylor College of Medicine and Miwatec Co. Ltd. Flow visualization measurements were conducted to compare the flow around the pivot for two impeller operational modes: the top and the bottom contact modes. In the top contact mode, one-way flow in the pivot gap due to the eccentric vortex was observed, and sufficient wall shear rate to prevent thrombus formation was attained around the bottom pivot for over 1,400 rpm. Computational fluid dynamic analyses confirmed that the causes of the eccentric vortex were the inlet eccentricity and the pressure imbalance in the volute.

Assisted Circulation↗

Hemolysis resulting from surface roughness under shear flow conditions using a rotational shear stressor.

The degree of hemolysis as a function of surface roughness value and roughened area under shear flow conditions was investigated using a rotational shear stressor. The shearing portion of the stressor is cone shaped in its upper and lower positions, with a cylindrical central section. Surface roughness was applied to the cylindrical section. Bovine blood was sheared for 30 min over a set of roughened surfaces of between arithmetic mean roughness (Ra) 0.1 and 0.8 mm covering 10% of the surface area of the cylindrical section (equivalent to 1.8% of the whole blood contact area) at a shear rate of 3750/s. The threshold value thus obtained for rapid increase in hemolysis was between Ra 0.6 and 0.8 mm. When sheared with a roughened surface of Ra 0.8 mm applied to the cylindrical surface at areas between 0 and 100% (equivalent to between 0 and 18% of the whole blood-contacting area), the hemolysis level did not increase from 10 to 100%, but a significant difference was obtained between 0 and 10%. This suggests that red blood cells were destroyed not by fatigue failure caused by rolling on the roughened surface, but due to the high shear stress generated by surface roughness. Moreover, it appears that the shear stress was generated over the entire cylindrical section, regardless of the area of surface roughness.

Animals↗

[A case of primary mediastinal choriocarcinoma].

A 30-year-old man presented with cough and bloody sputum. He brought a chest radiogram showing abnormal findings. His chest computed tomography revealed a large mediastinal mass and multiple nodular shadows in both lungs. The serum beta-HCG level was remarkably elevated, and physical examination revealed bilateral gynecomastia and right supraclavicular lymph node swelling. His lymph node was biopsied and choriocarcinoma was diagnosed. After 3 cycles of BEP therapy (cisplatin, etoposide, bleomycin), the tumors regressed and the serum beta-HCG level decreased. Although there were residual tumors and serum beta-HCG was mildly elevated, he refused additional therapy. The choriocarcinoma progessed rapidly again and he died seven months after his first visit. Primary mediastinal germ cell tumors are rare, and in particular the pure type of choriocarcinoma arising in the mediastinum is even rarer. Patients with mediastinal choriocarcinoma are mostly young men. The prognosis of primary mediastinal choriocarcinoma is still very poor despite the introduction of combination chemotheraphy including cisplatin. We report a case of primary mediastinum pure choriocarcinoma. Chemotherapy was effective for the patient, but he died because of recurrence after refusal of future treatment. Establishment of more effective treatment is necessary.

Adult↗

The crystal structure of human Atg4b, a processing and de-conjugating enzyme for autophagosome-forming modifiers.

Autophagy is an evolutionarily conserved pathway in which the cytoplasm and organelles are engulfed within double-membrane vesicles, termed autophagosomes, for the turnover and recycling of these cellular constituents. The yeast Atg8 and its human orthologs, such as LC3 and GABARAP, have a unique feature as they conjugate covalently to phospholipids, differing from ubiquitin and other ubiquitin-like modifiers that attach only to protein substrates. The lipidated Atg8 and LC3 localize to autophagosomal membranes and play indispensable roles for maturation of autophagosomes. Upon completion of autophagosome formation, some populations of lipidated Atg8 and LC3 are delipidated for recycling. Atg4b, a specific protease for LC3 and GABARAP, catalyzes the processing reaction of LC3 and GABARAP precursors to mature forms and de-conjugating reaction of the modifiers from phospholipids. Atg4b is a unique enzyme whose primary structure differs from that of any other proteases that function as processing and/or de-conjugating enzymes of ubiquitin and ubiquitin-like modifiers. However, the tertiary structures of the substrates considerably resemble that of ubiquitin except for the N-terminal additional domain. Here we determined the crystal structure of human Atg4b by X-ray crystallography at 2.0 A resolution, and show that Atg4b is a cysteine protease whose active catalytic triad site consists of Cys74, His280 and Asp278. The structure is comprised of a left lobe and a small right lobe, designated the "protease domain" and the "auxiliary domain", respectively. Whereas the protease domain structure of Atg4b matches that of papain superfamily cysteine proteinases, the auxiliary domain contains a unique structure with yet-unknown function. We propose that the R229 and W142 residues in Atg4b are specifically essential for recognition of substrates and catalysis of both precursor processing and de-conjugation of phospholipids.

Autophagy↗

Intra-specific variation in strategic ejaculation according to level of polyandry in Callosobruchus chinensis.

Optimal sperm allocation should differ according to the level of polyandry within a population, because the risk of sperm competition depends on the re-mating frequency of females. We compared the number of sperm ejaculated by males into the female reproductive organ between strains with different levels of polyandry in the adzuki bean beetle, Callosobruchus chinensis (Coleoptera: Bruchidae) when males were reared in different larval densities in a bean. The results showed that males derived from a population with a higher level of polyandry increased ejaculatory expenditure when they were reared under higher larval densities. We discuss the evolutionary correlation of ejaculatory expenditure to the level of polyandry.

Animals↗

Coordinated design of cofactor and active site structures in development of new protein catalysts.

New methods for the synthesis of artificial metalloenzymes are important for the construction of novel biocatalysts and biomaterials. Recently, we reported new methodology for the synthesis of artificial metalloenzymes by reconstituting apo-myoglobin with metal complexes (Ohashi, M. et al., Angew Chem., Int. Ed. 2003, 42, 1005-1008). However, it has been difficult to improve their reactivity, since their crystal structures were not available. In this article, we report the crystal structures of M(III)(Schiff base).apo-A71GMbs (M = Cr and Mn). The structures suggest that the position of the metal complex in apo-Mb is regulated by (i) noncovalent interaction between the ligand and surrounding peptides and (ii) the ligation of the metal ion to proximal histidine (His93). In addition, it is proposed that specific interactions of Ile107 with 3- and 3'-substituent groups on the salen ligand control the location of the Schiff base ligand in the active site. On the basis of these results, we have successfully controlled the enantioselectivity in the sulfoxidation of thioanisole by changing the size of substituents at the 3 and 3' positions. This is the first example of an enantioselective enzymatic reaction regulated by the design of metal complex in the protein active site.

Apoproteins↗

Mechanical circulatory support devices (MCSD) in Japan: current status and future directions.

The current status and future directions of mechanical circulatory support devices (MCSDs) in Japan are reviewed. Currently used clinical MCSDs, both domestic and imported systems and continuous flow devices that are coming into the clinical arena are emphasized. Clinical MCSDs include the extracorporeal pulsatile Toyobo and Zeon systems and the implantable Novacor and HeartMate I VE. A thorough review is presented of single-ventricle continuous flow MCSDs such as the Terumo DuraHeart and the SunMedical EVAHEART and the biventricular Miwatec/Baylor systems that are on the horizon. The future directions in management of end-stage cardiac patients with MCSDs are discussed, focusing on (1) device selection - pulsatile versus continuous flow devices; (2) single-ventricle support, biventricular support, or replacement; (3) bridge to transplantation, destination therapy, or bridge to recovery; and (4) government regulatory processes and the medical industry. We hope to promote the quality of life (QOL) of end-stage cardiac patients as well as the medical industry in Japan.

Animals↗

Hemolysis caused by surface roughness under shear flow.

In this study, the relationship between the degree of roughness of blood contact surfaces under laminar shear flow conditions and the level of hemolysis resulting from this roughness was investigated using a rotational shear stressor. Unlike previous in vitro experiments that used a pumped circuit, the level of hemolysis was directly evaluated under a constant shear flow. In total, 1.8% of the blood contact area was roughened to an arithmetic mean roughness (Ra) value of between 0.4 and 9.2 microm by machine processing and a shear load was applied for 30 min at a shear flow rate of 3750 s(-1). As a result, the threshold Ra value for the induction of hemolysis was found to be between 0.4 and 0.8 microm. In addition, the results of this experiment suggested that the high shear stress resulting from surface roughness plays a major role in determining the level of hemolysis caused by surface roughness.

Animals↗

Serum levels and pharmacodynamics of methotrexate and its metabolite 7-hydroxy methotrexate in Japanese patients with rheumatoid arthritis treated with 2-mg capsule of methotrexate three times per week.

Methotrexate (MTX) is the first-choice drug for rheumatoid arthritis (RA); however, the pharmacodynamics of MTX in Japanese patients with RA treated legitimately according to the government recommended dosage, 6 mg per week, are unknown. Methotrexate and its metabolite, 7-hydroxy MTX (7-OH MTX), were measured in sera of 16 outpatients with active RA in the first week of MTX treatment and 4-12 weeks after the introduction at 0, 1, 2, 4, and 8 h after administration of the first and the third 2-mg capsule, followed by sampling at 48, 96, and 168 h. The mean maximal serum drug concentration (mean C(max)) of MTX attained at 1-2 h after ingestion of the first capsule was 0.215 and 0.252 microM, respectively, in the first and the follow-up week. The mean C(max) after ingestion of the third capsule was 0.223 microM and 0.357 microM. The mean C(max) of 7-OH MTX was 0.0334 and 0.0289 microM for the first capsule, and 0.0495 and 0.0672 microM for the third capsule. The results indicate that MTX does not accumulate or deposit in the body of Japanese patients with RA when treated with 6 mg per week, and pharmacodynamics of MTX are comparable to those in overseas patients treated with 7.5 mg per week.

Journal Article↗

Reduced platelet adhesion to titanium metal coated with apatite, albumin-apatite composite or laminin-apatite composite.

Titanium metal coated with apatite (HA-Ti), albumin-apatite composite (AA-Ti) or laminin-apatite composite (LA-Ti) was prepared by the immersion of NaOH- and heat-treated titanium metal in a calcium phosphate solution, or one supplemented with albumin or laminin. Platelet adhesion to the obtained materials under flow conditions was investigated in real time using a cone- and plate-type viscometer and fluorescence labeled platelets. Adhesion and activation of the platelets on the HA-Ti, AA-Ti and LA-Ti were definitely suppressed as compared with those on untreated titanium metal with a mirror surface. Furthermore, the numbers of platelets adhered to AA-Ti and LA-Ti are smaller than those adhered to HA-Ti, although the differences were not statistically significant. These findings suggest that HA-Ti, AA-Ti and LA-Ti, especially AA-Ti and LA-Ti, would exhibit thromboresistance that is superior to commercially pure titanium metal in terms of platelet adhesion.

Adult↗

Predictive factors for long-term outcome of stereoacuity in Japanese patients with pure accommodative esotropia.

PURPOSE: To find clinical factors related to the long-term outcome of stereoacuity in Japanese patients with pure accommodative esotropia, including both the refractive type and the nonrefractive type. METHODS: The medical charts of 19 Japanese patients (8 boys and 11 girls) with pure accommodative esotropia who were followed for 10 years or more at Okayama University Hospital were reviewed retrospectively. Refractive accommodative esotropia was diagnosed in 8 patients while nonrefractive accommodative esotropia was diagnosed in 11 patients. The patients were divided into two groups, based on a stereoacuity of 120 seconds of arc or better versus 240 seconds of arc or worse as measured by the TNO test at the final visit, and the clinical factors were compared between the two groups. RESULTS: Clinical factors related to a stereoacuity of 240 seconds of arc or worse at the final visit were higher accommodative convergence to accommodation (AC/A) ratios at 6 years of age (p = 0.05), larger residual esodeviations at distance under full correction with glasses at 8 years of age (p = 0.03), and larger residual esodeviations at near at 6 years of age (p = 0.01, Mann-Whitney U-test). Overall, patients with nonrefractive accommodative esotropia tended to show poor levels of stereoacuity at the final visit compared to those with refractive accommodative esotropia (p = 0.059, Fisher exact probability test). CONCLUSION: This is the first study of the long-term visual outcome in Japanese patients with pure accommodative esotropia including both refractive and nonrefractive types. To obtain better levels of stereoacuity, the residual esodeviations at near and at distance should be kept as small as possible under full correction with glasses, including bifocals, especially at the ages of 6 and 8 years.

Accommodation, Ocular↗

The hemolytic characteristics of monopivot magnetic suspension blood pumps with washout holes.

The hemolytic characteristics of monopivot magnetic suspension blood pumps as a function of impeller washout hole configuration and female pivot shape are observed. The pump impellers are designed with three washout hole configurations for blood circulation, and four female pivot shapes to reduce blood stagnation and to enhance antithrombogenicity. The hemolytic characteristics of the monopivot pumps were observed to be better than those of a currently available commercial centrifugal blood pump, BP-80, and changed to be nearly equal when the female pivot shape was changed. This indicates that hemolysis in monopivot pumps is mainly caused by shear stress between the male and female pivots.

Animals↗

Stereoselective synthesis of optically active disilanes and selective functionalization by the cleavage of silicon-naphthyl bonds with bromine.

Optically active disilanes with one chiral silicon center, (R)-1,2-dimethyl-1-(naphth-1-yl)-1,2,2-triphenyldisilane and (R)-1,2,2-trimethyl-2-(4-methoxynaphth-1-yl)-1-(naphth-1-yl)-1-phenyldisilane, were obtained by the reaction of (S)-methyl(naphth-1-yl)phenylchlorosilane (> 99% ee) with methyldiphenylsilyllithium or by the reaction of methyldiphenylchlorosilane with optically active (S)-methyl(naphth-1-yl)phenylsilyllithium and by the reaction of (S)-methyl(naphth-1-yl)phenylchlorosilane (> 99% ee) with dimethyl(4-methoxynaphth-1-yl)silyllithium. Under the optimized conditions, the reactions proceeded with almost complete inversion for the cholorosilanes and retention for the silyl anions. Optically active disilanes with two chiral centers, (1R,2R)-1,2-dimethyl-1,2-di(naphth-1-yl)-1,2-diphenyldisilane and (1S,2S)-1,2-di(4-methoxynaphth-1-yl)-1,2-dimethyl-1,2-diphenyldisilane, were obtained in high optical purity by the reactions of corresponding optically active halogenosilanes (Cl or F) with optically active silyllithiums. The silicon-silicon bond and the silicon-naphthyl bond of (R)-1,1,2-trimethyl-1,2-di(naphth-1-yl)-2-phenyldisilane and (1R,2R)-1,2-dimethyl-1,2-di(naphth-1-yl)-1,2-diphenyldisilane were cleaved without selectivity on bromination. The silicon-(4-methoxynaphth-1-yl) bond of (R)-1,2,2-trimethyl-2-(4-methoxynaphth-1-yl)-1-(naphth-1-yl)-1-phenyldisilane was regiospecifically cleaved, followed by the stereoselective cleavage of the remaining chiral silicon-naphthyl bond (94% inversion). Although the silicon-(4-methoxynaphth-1-yl) bonds of (1S,2S)-1,2-di(4-methoxynaphth-1-yl)-1,2-dimethyl-1,2-diphenyldisilane (> 99% ee) were regioselectively cleaved without silicon-silicon bond scission, remarkable racemization could not be avoided during the one-pot reaction.

Journal Article↗

Crystal structures of artificial metalloproteins: tight binding of FeIII(Schiff-Base) by mutation of Ala71 to Gly in apo-myoglobin.

Apo-myoglobin (apo-Mb) and apo-A71GMb were successfully reconstituted with FeIII(salophen) (1) (salophen = N,N'-bis(salicylidene)-1,2-phenilenediamine), Fe(III)(3,3'-Me2-salophen) (2), and FeIII(5,5'-t-Bu2-salophen) (3). The crystal structure of 2.apo-A71GMb shows the tight binding of the complex in the Mb cavity, while in wild-type apo-Mb it is highly disordered due to the steric repulsion with Ala71. Furthermore, the structure of 2.apo-A71GMb suggests a possible accommodation of a small substrate in the cavity. In fact, the cyanide association rate constant of 2.apo-A71GMb is 216-fold larger compared to that of 2.apo-Mb. These results provide us principles for the noncovalent fixation of synthetic metal cofactors at the desired positions in protein matrixes.

Alanine↗

Hepatic artery pseudoaneurysm associated with cholecystitis that ruptured into the gallbladder.

Pseudoaneurysm of the hepatic artery due to cholecystitis may be very rare, and in our survey of the literature, the present case report is the first case of such a pseudoaneurysm. A 64-year-old woman presented with upper gastrointestinal bleeding and severe epigastric pain. Upper gastrointestinal tract endoscopy revealed blood coming out of the papilla of Vater. Color-Doppler ultrasound imaging showed a pulsatile wave pattern in an echogenic lesion inside the gallbladder. Contrast-enhanced computed tomography demonstrated a 3-cm pseudoaneurysm in the distended gallbladder. Angiography disclosed extravasation originating from the right hepatic artery. Emergency selective transcatheter arterial embolization was performed, with intravascular stainless steel microcoils, and complete occlusion of the pseudoaneurysm was achieved. The patient underwent cholecystectomy with resection of the extrahepatic bile duct and biliary reconstruction in a Roux-en-Y fashion. Macroscopically, the resected gallbladder contained clotted blood and multiple cholesterol stones. Microscopically, the mucosa of the gallbladder showed extensive necrosis and many inflammatory cells. The final diagnosis was pseudoaneurysm of the hepatic artery associated with calculous gangrenous cholecystitis. Although the mechanism of the pseudoaneurysm remains speculative, severe inflammatory reaction in the gallbladder may have infiltrated the liver parenchyma and may have eroded the wall of the hepatic artery, thus forming a pseudoaneurysm. Hemobilia is one of the important differential diagnoses when unexplained gastrointestinal bleeding is observed, especially in patients with hepatobiliary diseases.

Aneurysm, False↗

The technique of ophthalmic arterial infusion therapy for patients with intraocular retinoblastoma.

Recently, there has been increasing interest in treating intraocular retinoblastoma with systemic chemotherapy combined with focal laser therapy and cryotherapy instead of radiotherapy. We developed a system of selective ophthalmic arterial infusion (SOAI) therapy, administering melphalan, the agent which had the greatest effect on retinoblastoma in a clonogenic assay. The SOAI system consists of a combination of a micro-balloon, a guiding catheter, and a flushing hub. After selective catheterization to the cervical segment of the internal carotid artery by the guiding catheter, the micro-balloon was propelled to the portion just distal to the orifice of the ophthalmic artery. During temporary occlusion of the internal carotid artery, melphalan was infused from the introduced catheter tip. We treated 187 patients with intraocular retinoblastoma with SOAI; 563 SOAIs were performed for 610 eyes. The technical success rate was 97.51%. Fourteen examinations failed. No significant complication due to catheterization (including brain infarction) was detected. SOAI, using the balloon occlusion technique, is safe, and its use will prevent the side effects that occur with systemic chemotherapy, and eliminate the need for irradiation and enucleation.

Antineoplastic Agents, Alkylating↗