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Biomedical subjects

Takashi Sakai

Publications and source records attributed to Takashi Sakai.

At least 19 recordsLinked to original sources
PubMed2006

Versatile and practical chiral shift reagent with hydrogen-bond donor/acceptor sites in a macrocyclic cavity.

[structure: see text] Bifunctional macrocycle 1 with C2 symmetry was newly synthesized. NMR studies demonstrated that receptor 1 functions as a chiral shift reagent (solvating agent) that is highly effective for a wide range of chiral compounds having a carboxylic acid, oxazolidinone, lactone, alcohol, sulfoxide, sulfoximine, isocyanate, or epoxide functionality. Binding constants were determined to investigate the binding behavior of 1.

Journal Article↗
PubMed2006

Potential role for astroglial D-amino acid oxidase in extracellular D-serine metabolism and cytotoxicity.

D-amino acid oxidase (DAO) is a flavoenzyme that catalyzes the oxidation of D-amino acids. In the brain, gene expression of DAO is detected in astrocytes. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) receptor. In a search for the physiological role of DAO in the brain, we investigated the metabolism of extracellular D-serine in glial cells. Here we show that after D-serine treatment, rat primary type-1 astrocytes exhibited increased cell death. In order to enhance the enzyme activity of DAO in cells, we established stable rat C6 glial cells overexpressing mouse DAO designated as C6/DAO. Treatment with a high dose of D-serine led to the production of hydrogen peroxide (H(2)O(2)) followed by apoptosis in C6/DAO cells. Among the amino acids tested, D-serine specifically exhibited a significant cell death-inducing effect. DAO inhibitors, i.e., sodium benzoate and chlorpromazine, partially prevented the death of C6/DAO cells treated with D-serine, indicating the involvement of DAO activity in d-serine metabolism. Overall, we consider that extracellular D-serine can gain access to intracellular DAO, being metabolized to produce H(2)O(2). These results support the proposal that astroglial DAO plays an important role in metabolizing a neuromodulator, D-serine.

Amino Acids↗
PubMed2006

The custom femoral component is an effective option for congenital hip dysplasia.

Although custom-designed femoral prostheses seem more likely to be successful than off-the-shelf components for treatment of patients with osteoarthritis secondary to congenital hip dysplasia, published short-term results of custom stems with a smooth surface or titanium proximal mesh pads are no better than results for off-the-shelf components. To determine whether cementless custom femoral components with sandblasted surfaces provide better results than other custom stems, we prospectively evaluated 77 consecutive patients (99 hips) with a mean age of 54 years who had osteo-arthritis secondary to congenital hip dysplasia. The mean followup was 9 years 3 months. Forty-seven hips were classified as having Crowe Type I deformity, 41 were classified as having Crowe Type II deformity, and 11 were classified as having Crowe Type III deformity. The average Harris hip score was 97.6 points at the last followup. Radiographically, 88 hips (89%) showed bone ongrowth, seven hips (7%) showed stable fibrous fixation, and four hips (4%) showed unstable fixation. There were two intraoperative femoral fractures and varus malpositioning of four stems in the hips with stable fibrous fixation and the unstable hips. One femoral component was revised 6 years postoperatively. Although the anatomic cementless custom-designed femoral components with sandblasted surfaces provided favorable results in patients with Crowe Types I, II, and III deformities, intra-operative technical errors prevented bone ongrowth fixation.

Adult↗
PubMed2006

Attenuation of MPTP-induced neurotoxicity and locomotor dysfunction in Nucling-deficient mice via suppression of the apoptosome pathway.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity is one of the experimental models most commonly used to study the pathogenesis of Parkinson's disease (PD). Although the biochemical mechanisms underlying the cell death induced by MPTP remain to be clarified, it has been found that the mitochondrial apoptotic signaling pathway plays an important role in the neurotoxicity of MPTP. Nucling is a novel type of apoptosis-associated molecule, essential for cytochrome c, apoptosis protease activating factor 1 (Apaf-1), pro-caspase-9 apoptosome induction and caspase-9 activation following pro-apoptotic stress. Here we found that Nucling-deficient mice treated with MPTP did not exhibit locomotor dysfunction in an open-field test. The substantia nigra dopaminergic neurons of Nucling-deficient mice were resistant to the damaging effects of the neurotoxin MPTP. Up-regulated expression of apoptosome was attenuated in Nucling-deficient mice treated with MPTP. These results indicate an important role for Nucling in MPTP-induced neuronal degeneration and suggest that the suppression of Nucling would be of therapeutic benefit for the treatment of neurodegeneration in PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Production of sepedonin by Sepedonium chrysospermum NT-1 in submerged culture.

Strains of Sepedonium chrysospermum and the anamorph strain of Hypomyces chrysospermus (congruent with Apiocrea chrysosperma) were isolated and purified from parasitic filamentous fungi on the fruiting bodies of Boletaceae, such as the Gyroponus and Suillus genera in Japan, and identified from formations of conidia and chlamydospores. It is known that these strains produce sepedonin. S. chrysospermum NT-1 strain was selected from these strains and isolated. As the optimum medium (CY-1 medium), 0.1% yeast extract was added to the fruiting-body-forming medium (C medium) of Schizophyllum commune. After 8 days of growth on CY-1 medium, the yield of sepedonin was about 34 mg per 2 g of glucose added. This sepedonin seemed to inhibit the growth of various gram-positive and gram-negative bacteria, yeasts and molds.

Anti-Infective Agents↗
PubMed2005

Suzuki-Miyaura coupling reaction using pentafluorophenylboronic acid.

[reaction: see text] We have found new conditions for the Suzuki-Miyaura coupling reaction applicable to pentafluorophenylboronic acid (C(6)F(5)B(OH)(2)) (1), which is an inactive substrate under normal conditions. The reactions of 1 with phenyl iodide or bromide under Pd(PPh(3))(4)/CsF/Ag(2)O or Pd(2)(dba)(3)/P(t-Bu)(3)/CsF/Ag(2)O catalytic system conditions gave 2,3,4,5,6-pentafluoro-1,1'-biphenyl (3a) in more than 90% yields. Combination of CsF and Ag(2)O was essential for promoting these reactions.

Journal Article↗
PubMed2005

Highly sensitive chiral shift reagent bearing two zinc porphyrins.

A new type of chiral receptor (R,R)- or (S,S)-1b with C(2) symmetry was synthesized. An induced-fit type of binding behavior of 1b for diamines was revealed by CD spectroscopy. NMR studies demonstrated that 1b can function as a highly sensitive chiral shift reagent for the determination of the enantiomeric purity of chiral diamines, aziridine, and isoxazoline at the microgram level. [structure: see text]

Journal Article↗
PubMed2005

Lipase-catalyzed resolution of (2R*,3S*)- and (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol at low temperatures and determination of the absolute configurations of the four stereoisomers.

[reaction: see text] Lipase-catalyzed resolution of (2R*,3S*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-2, at low temperatures gave synthetically useful (2R,3S)-2 and its acetate (2S,3R)-2a with (2S)-selectivity (E = 55 at -40 degrees C), while a similar reaction of (2R*,3R*)-3-methyl-3-phenyl-2-aziridinemethanol, (+/-)-3, gave (2S,3S)-3 and its acetate (2R,3R)-3a with (2R)-selectivity (E = 73 at -20 degrees C). Compound (+/-)-2 was prepared conveniently via diastereoselective addition of MeMgBr to tert-butyl 3-phenyl-2H-azirine-2-carboxylate, (+/-)-1a, which was successfully prepared by the Neber reaction of oxime tosylate of tert-butyl benzoyl acetate 7a. The tert-butyl ester was requisite to promote this reaction. For determination of the absolute configuration of (2S,3R)-2a, enantiopure (2S,3R)-2 was independently prepared in three steps involving diastereoselective methylation of 3-phenyl-2H-azirine-2-methanol, (S)-10, with MeMgBr. The absolute configuration of (2S,3S)-3 was determined by X-ray analysis of the corresponding N-(S)-2-(6-methoxy-2-naphthyl)propanoyl derivative (S,S,S)-13.

Aziridines↗
PubMed2005

Simple and efficient fabrication of room temperature stable electride: melt-solidification and glass ceramics.

Electrides are ionic compounds in which electrons act as anions. These compounds are expected to have interesting properties arising from their exotic structure. The fatal drawbacks of the thermal and chemical instability of organic electrides were resolved by the synthesis of a room temperature (RT) stable electride using single crystalline 12CaO.7Al2O3 (C12A7) with a nanoporous structure and the chemical treatments for a long duration. However, an innovative fabrication method is obviously required for practical applications such as cold electron-emitter and thermionic devices. Herein we report a simple synthesis for polycrystalline C12A7 electrides with a moderate electronic conductivity via a strongly reducing C12A7 "melt", i.e., direct solidification of the melt or crystallization of the transparent glass. Generation of carrier electrons and precipitation of the C12A7 phase from the strongly reducing melt and glass are likely associated with the incorporation of carbon-related anions for stabilizing the C12A7 phase and keeping the mobile electrons in C12A7. These findings will be broadly utilized for applications by mass production in a desired shape and dimension, facilitating the research of electrides.

Journal Article↗
PubMed2005

Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non-small cell lung cancer--in correlation with the tumoral expression of thymidylate synthase and dihydropyrimidine dehydrogenase.

5-Fluorouracil (5-FU) and its derivatives have been used worldwide for the treatment of several malignancies in solid organs. The effectiveness of these drugs is well proven in gastrointestinal malignancy, and has been reported upon the inverse correlation with the tumoral expression of dihydropyrimidine dehydrogenase (DPD). However, the significance of DPD expression in 5-FU based chemotherapy has not been well investigated in non-small cell lung cancer (NSCLC). We examined enzymatic activities and immunohistochemical expression of thymidylate synthase (TS) and DPD in 84 cases of NSCLC. In vitro sensitivity for 5-FU was tested in 53 cases of them to evaluate these predictive values for effectiveness of 5-FU. Efficacy of 5-chloro-2,4-dihydroxypyridine (CDHP), potent DPD inhibitor, was also examined in 27 cases of them. There was a reversal correlation between protein expression of DPD and sensitivity to 5-FU (r = -0.65; p < 0.001). Six (33.3%) of 18 cases with strong expression of DPD showed 10% or more increment of the anti-tumor effect by adding CDHP to 5-FU. DPD inhibitory fluoropyrimidine and examination of the tumoral expression of DPD might be a promising chemotherapeutic strategy in NSCLC.

Adult↗
PubMed2005

Effect of sucrose fatty acid esters on transdermal permeation of lidocaine and ketoprofen.

The effect of sucrose fatty acid esters on transdermal permeation of lidocaine (LC) and ketoprofen was examined. A drug solution was applied to excised hairless mouse skin pretreated with a sugar ester solution to examine the direct effects of the sugar esters on skin permeability. LC was applied with a pH 6 buffer solution (98.8% ionized), pH 10 buffer solution (99.2% unionized), or propylene glycol, while KP was applied with a pH 6 buffer solution (99.1% ionized), pH 2 buffer solution (98.9% unionized), or propylene glycol. Pretreatment with J-1216 (sucrose laurate, HLB = 16) or J-1205 (sucrose laurate, HLB = 5) significantly increased the permeation of LC from the pH 6 solution and KP from propylene glycol, respectively. The permeability coefficients of the ionized and unionized LC and KP were calculated from the permeability data. The ionized LC and KP permeated even through skin not pretreated with sugar esters, although the permeability coefficients were 24 times and 38 times less than those of the unionized LC and KP, respectively. J-1216 pretreatment increased the permeability of ionized LC from aqueous vehicle 2.7 fold. In the next series of experiments, we formulated 1.5% of J-1205 and J-1216 in various vehicles to examine their effect on the permeation of LC applied on the excised hairless mouse skin with no pretreatment. The results coincided with the results of the pretreatment experiment, and the effect of J-1205 in propylene glycol was more remarkable than that observed in the pretreatment study. When these sugar esters were dissolved in propylene glycol at 1.5%, J-1205 increased significantly the KP permeation rate as well as LC permeation rate, suggesting that the combination of J-1205 and propylene glycol would be a potent vehicle for transdermal formulations.

Administration, Cutaneous↗
PubMed2004

Reestimation of the Taft's substituent constant of the pentafluorophenyl group.

The Taft's substituent constant of the pentafluorophenyl group (sigma(C(6)F(5))) was reestimated to be 1.50 by correlation between IR spectral data (v(C)(=)(O)) and sigma constants for a series of esters (involving the pentafluorobenzyl group) of 3-phenylpropanoic acid and butanoic acid. The possibility of the disturbance of the correlation by the intramolecular pi-pi interaction between C(6)F(5) and C(6)H(5) groups in pentafluorobenzyl 3-phenylpropanoate was excluded by ab initio and DFT calculations of the stable conformations and their carbonyl frequencies. The reestimated sigma(C(6)F(5)) value was used for calculation of the pK(a) value of pentafluorobenzyl alcohol [14.5 (or 14.3)].

Journal Article↗
PubMed2004

Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis.

Nucling is a novel protein isolated from murine embryonal carcinoma cells with an up-regulated expression during cardiac muscle differentiation. We show here that Nucling was up-regulated by proapoptotic stimuli and important for the induction of apoptosis after cytotoxic stress. We further demonstrated that overexpressed Nucling was able to induce apoptosis. In Nucling-deficient cells, the expression levels of Apaf-1 and cytochrome c, which are the major components of an apoptosis-promoting complex named apoptosome, were both down-regulated under cellular stress. A deficiency of Nucling also conferred resistance to apoptotic stress on the cell. After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex, suggesting that Nucling might be a key molecule for the formation and maintenance of this complex. Nucling induced translocation of Apaf-1 to the nucleus, thereby distributing the Nucling/Apaf-1/pro-caspase-9 complex to the nuclear fraction. These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis.

Alleles↗
PubMed2004

Nucling mediates apoptosis by inhibiting expression of galectin-3 through interference with nuclear factor kappaB signalling.

Nucling is a novel apoptosis-associated molecule, which is involved with cytochrome c /Apaf-1/caspase-9 apoptosome induction following pro-apoptotic stress. In the present study, we show first that Nucling is able to interact with galectin-3. Galectin-3 is known to participate in many biological processes, including apoptotic cell death. Nucling was found to down-regulate the expression level of galectin-3 mRNA/protein. Nucling-deficient cells, in which galectin-3 expression is up-regulated, appeared to be resistant to some forms of pro-apoptotic stress as compared with wild-type cells. In addition, the preputial gland from Nucling-deficient mice expressed a significant level of galectin-3 and exhibited a high incidence of inflammatory lesions, indicating that Nucling plays a crucial role in the homoeostasis of this gland by interacting with the galectin-3 molecule and regulating the expression level of galectin-3. Up-regulation of galectin-3 was also observed in the heart, kidney, lung, testis and ovary of the Nucling-deficient mice. In order to confirm the functional interaction between Nucling and galectin-3, a well-documented candidate for the mediator of galectin-3 expression, NF-kappaB (nuclear factor kappaB), was investigated as well. Nucling was shown to interfere with NF-kappaB activation via the nuclear translocation process of NF-kappaB/p65, thus inhibiting the expression of galectin-3. Taken together, we propose that Nucling mediates apoptosis by interacting and inhibiting expression of galectin-3.

Animals↗
PubMed2004

Acute calcific tendinitis of the gluteus medius: a case report with serial magnetic resonance imaging findings.

A case of calcific tendinitis of the gluteus medius is presented. Calcification was evident in the soft tissue adjacent to the greater trochanter on plain radiographs. On the initial magnetic resonance images (MRI), inflammatory edematous change was detected not only in the gluteus medius but also in the bone marrow of the greater trochanter, corresponding to the painful area. Three months later, calcification disappeared on plain radiographs and the femur showed normal signal intensity on MRI. Initial MRI excluded other diseases' including infection and bone tumor, and serial MRI confirmed that the change in extraosseous and intraosseous findings were in accordance with self-limiting clinical symptoms.

Acute Disease↗
PubMed2004

Bilateral achilles tendon ruptures in a patient with ochronosis: a case report.

We report the case of a 67-year-old man with ochronosis who had bilateral Achilles tendon ruptures. We reconstructed the Achilles tendon using pull-out wiring for the right side and an anchoring system for the left side, and reinforced the repair site using the peroneus brevis tendon for both sides. He could walk without a cane at 3 months postoperatively. Tendon ruptures in patients with ochronosis should be treated as pathologic ruptures because histologic examination reveals that both ends of the ruptured tendon and the insertion site at the calcaneus have extensive black pigment depositions where homogentisic acid and its metabolites have accumulated, and there are no normal collagen bundles present. Even if an Achilles tendon rupture is clinically diagnosed as an acute injury, the ruptured Achilles tendon should be primarily repaired and reinforced with autologous tissue because there are a few viable cells at the ruptured site, and because the tendon ruptures mainly at the insertion site of the calcaneus. Although this is a preliminary report, the short-term result is good and the reconstructed sites have showed no rerupture.

Achilles Tendon↗