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Biomedical subjects

Makoto Yasuda

Publications and source records attributed to Makoto Yasuda.

At least 19 recordsLinked to original sources
PubMed2005

Reductive cross-aldol reaction using bromoaldehyde and an aldehyde mediated by germanium(II): one-pot, large-scale protocol.

[reaction: see text] The reaction of alpha-bromoaldehyde with aldehyde in the presence of GeCl(2)-dioxane gave the syn-selective cross-aldol equivalent. A catalytic amount of Bu(4)NBr improved the yield and selectivity. The initially formed aldol adduct (beta-germoxyaldehyde) did not suffer from over-reaction. This system enabled an intramolecular aldol reaction to give cyclic compounds effectively. One-pot synthetic methodology including bromination of aldehyde followed by cross-aldol reaction with the second aldehyde was successful on a large-scale.

Journal Article↗
PubMed2005

Identification of essential amino acid residues of the NorM Na+/multidrug antiporter in Vibrio parahaemolyticus.

NorM is a member of the multidrug and toxic compound extrusion (MATE) family and functions as a Na+/multidrug antiporter in Vibrio parahaemolyticus, although the underlying mechanism of the Na+/multidrug antiport is unknown. Acidic amino acid residues Asp32, Glu251, and Asp367 in the transmembrane region of NorM are conserved in one of the clusters of the MATE family. In this study, we investigated the role(s) of acidic amino acid residues Asp32, Glu251, and Asp367 in the transmembrane region of NorM by site-directed mutagenesis. Wild-type NorM and mutant proteins with amino acid replacements D32E (D32 to E), D32N, D32K, E251D, E251Q, D367A, D367E, D367N, and D367K were expressed and localized in the inner membrane of Escherichia coli KAM32 cells, while the mutant proteins with D32A, E251A, and E251K were not. Compared to cells with wild-type NorM, cells with the mutant NorM protein exhibited reduced resistance to kanamycin, norfloxacin, and ethidium bromide, but the NorM D367E mutant was more resistant to ethidium bromide. The NorM mutant D32E, D32N, D32K, D367A, and D367K cells lost the ability to extrude ethidium ions, which was Na+ dependent, and the ability to move Na+, which was evoked by ethidium bromide. Both E251D and D367N mutants decreased Na+-dependent extrusion of ethidium ions, but ethidium bromide-evoked movement of Na+ was retained. In contrast, D367E caused increased transport of ethidium ions and Na+. These results suggest that Asp32, Glu251, and Asp367 are involved in the Na+-dependent drug transport process.

Amino Acid Sequence↗
PubMed2004

In- or in(I)-employed diastereoselective Reformatsky-type reactions with ketones: 1H NMR investigations on the active species.

An efficient In- or In(I)-based stereoselective C-C bond formation is reported; the diastereoselective Reformatsky-type reactions of ketones. The predominant formations of anti isomers, confirmed by the X-ray structure analyses of ester derivatives of respective alcohols 9a(1)() and 13a(1)(), conclusively revealed the stereochemistry of the reaction path. (1)H NMR investigations revealed the formation of two types of alpha-metalated transient species from alpha-halo esters with In or In(I) halides. [reaction: see text]

Journal Article↗
PubMed2004

Indium-catalyzed direct chlorination of alcohols using chlorodimethylsilane-benzil as a selective and mild system.

The InCl3-catalyzed reaction of alcohols with chlorodimethylsilane (HSiMe2Cl) in the presence of benzil gave the corresponding organic chlorides under mild conditions. Benzil significantly changes the reaction course because the reducing product through dehydroxyhydration was obtained in the absence of benzil. The secondary or tertiary alcohols were effectively chlorinated. The substrates bearing acid-sensitive functional groups were also applied to this system. The highly selective chlorination of the tertiary site was observed in the competitive reaction between tertiary and primary alcohols. The highly coordinated hydrosilane generated from benzil and HSiMe2Cl is an important intermediate.

Journal Article↗
PubMed2004

Allylic tantalums as highly imine-selective reagents.

A practical method for the allylation of low electrophilic N-aliphatic imines was established by allylic tantalum. This is a superior methodology compared with conventional ones in terms of wide applicability to imines.

Journal Article↗
PubMed2004

Drug sensitivity-related benefit of systematic lymphadenectomy during cytoreductive surgery in optimally debulked stages IIIc and IV ovarian cancer.

OBJECTIVE: The purpose of this study is to assess the survival experience following systematic lymphadenectomy (LNX) in conjunction with primary but optimal cytoreductive surgery in advanced epithelial ovarian cancer (OC) patients when followed by intensive chemotherapy. METHODS: This is a retrospective analysis of all women with OC who were treated in our institution between 1992 and 2000. A total of 98 patients with stages IIIc-IV of OC underwent primary cytoreductive surgery which was 'optimal' (<1 cm residual disease). All patients subsequently received postoperative platinum-containing chemotherapy. Group I, consisting of 51 patients underwent LNX; Group II, consisting of 47 patients did not undergo LNX. The percentage of patients failing to respond to chemotherapy in each group was similar. Each group had statistically equivalent age, stage, regimens of chemotherapy performed, and all other known prognostic factors. RESULTS: No survival benefit could be seen in platinum-sensitive patients. However, in patients who failed to respond to chemotherapy, the 2-year progression-free survival (PFS) (42.8% vs. 14.3%) and overall survival (OS) (51.2% vs. 28.8%) was quite different. LNX significantly improved those of drug-resistant patients when optimal cytoreductive surgery was performed [P = 0.008, risk ratio (rr) = 2.675, 95% confidence interval (CI) = 1.251-5.724]. Cox's proportional analysis shows that LNX was one of the three most significant covariate with the tumor grade and the number of postoperative residual lesions. CONCLUSIONS: The results show that LNX might be of benefit in patients who have optimal primary cytoreductive surgery and who do not respond to platinum-based chemotherapy.

Adult↗
PubMed2004

Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma.

OBJECTIVE: To evaluate the significance of the expression of HER-2/neu as a prognostic factor, we retrospectively examined its overexpression rates chiefly in ovarian clear cell adenocarcinoma (CCA) and their relationships with FIGO stage, lymph node metastasis, and prognosis. METHODS: In addition to 90 specimens of CCA (stage I, 52; stage II, 7; stage III, 28; stage IV, 3) obtained between 1987 and 2002, 19 specimens of serous adenocarcinoma (S), 19 specimens of mucinous adenocarcinoma (M), and 19 specimens of endometrioid adenocarcinoma (E) collected at initial surgery were studied. The expression of HER-2/neu was immunohistologically scored on a scale of 0 to 3+ according to the HercepTest scoring system, and 2+ and 3+ were regarded as overexpression. The relationship between HER-2/neu overexpression and outcome was evaluated by the Kaplan-Meier method and the log-rank test. The relationship with advanced-stage cancer was analyzed by Fisher's exact test. The relationships with lymph node metastasis and histologic types were compared by the t test. RESULTS: The rate of HER-2/neu overexpression in CCA was 45.6% (0, 1+, 2+, and 3+ in 14, 35, 36, and 5 cases, respectively), and no differences in the overexpression rate were noted among histologic types: 52.7% in S, 42.1% in M, and 26.4% in E. In CCA, no association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.5708), FIGO stage (P = 0.5147), or lymph node metastasis (P = 0.3624). CONCLUSION: The absence in CCA of an association between HER-2/neu overexpression and outcome, stage, or lymph node metastasis indicates that HER-2/neu overexpression is not a prognostic risk factor.

Adenocarcinoma, Clear Cell↗
PubMed2004

Establishment and characterization of a nerve cell line (NC-HIMT) from HIMT cells derived from a human ovarian immature teratoma with special reference to the induction of neuron differentiation by retinoic acid.

A nerve cell line designated NC-HIMT was established from a HIMT cell line derived from a benign ovarian, three germ layer immature teratoma removed from a 21-year-old Japanese female. The HIMT cells were elongated, ellipsoid or spherical in shape, whose karyotype was on the high side of normal diploidy. Small amounts of retinoic acid enhanced differentiation and maturation of the HIMT cells into nervous tissue, and the NC-HIMT cell line was established by the colony isolating technique when the HIMT cell line was cultured in the presence of retinoic acid-supplemented medium. After establishment, the NC-HIMT cell line was cultured and maintained in retinoic acid-free growth medium. Even though these cells were cultured without retinoic acid, the phenotype of nerve cells remained and the cells were also maintained in a state of high normal diploidy. The nerve cells contacted each other with their long cell projections and formed networks. Immunocytochemical observations using anti-bovine NSE, alpha-internexin, neurofilament 200kD, peripherin and GFAP confirmed that the cells were either nerve cells or glia cells. These results assume that HIMT cells, which were derived from an immature teratoma, have progenitor and/or stem cells which can differentiate into nerve and/or glial cells.

Adult↗
PubMed2004

Establishment and characterization of JHUCS-1 cell line derived from carcinosarcoma of the human uterus.

The cell line designed JHUCS-1 was established from a carcinosarcoma (malignant mixed mesodermal tumor) of the uterus that was surgically removed from a 57-year-old Japanese woman. We carefully examined the histopathology of the original tumor after the cell line was established and noted differentiation into a neuroendocrine carcinoma within the tumor's epithelial components. Immunohistochemical staining of the tumorous tissue that had been heterotransplanted was positive for Leu7. Additionally, secretary granules were observed in the grafted cells as determined by electron microscopy. These results support the existence of neuroendocrine cells within the JHUCS-1 cell line.

Animals↗
PubMed2004

[Docetaxel and carboplatin for epithelial ovarian cancer].

We report herein on the efficacy and toxicity of docetaxel and carboplatin in patients with epithelial ovarian cancer. Fifteen patients with FIGO stage I c-IV epithelial ovarian cancer were administered docetaxel (70 mg/m2) and carboplatin (AUC 5) every 3 weeks as 1 course. Eleven patients received this regimen as a first-time chemotherapy, and the other 4 as therapy for recurrence. Seven patients were evaluated for response. Of these, 6 achieved complete response and the other a partial response. CA 125 response was seen in 2 of 8 patients who did not have visible tumors. Our toxicity findings include the following: grade 3 and 4 neutropenia (86.7%), hypersensitive reaction (13.3%), grade 2 alopecia (13.3%), and no edema. Docetaxel and carboplatin are actively used in ovarian cancer, with the major toxicity being bone marrow suppression. But we were able to control myelosuppression with G-CSF. Hypersensitivity reactions were frequent, we thought pre-medication. This chemotherapy combination appears effective for epithelial ovarian cancer.

Adult↗
PubMed2003

Trigeminal nerve-mediated reflex arterial blood pressure decrease and vasodilatation in lower lip of the rabbit.

We measured the effects of electrical stimulation of the central cut end of the lingual nerve on lower lip blood flow (LBF) and on arterial blood pressure in urethane-anesthetized, artificially ventilated, cervically vagosympathectomized rabbits. Different effects were observed depending on the stimulus frequency. Increasing the stimulus frequency above 5 Hz produced progressively larger ipsilateral LBF increases until the optimal frequency was reached at 20 Hz. In contrast, stimulation at above 0.5 Hz evoked progressively larger decreases in both contralateral LBF and arterial blood pressure until the optimal frequency was reached at around 10 and 2 Hz, respectively. Thus, the optimal stimulus frequencies for the ipsilateral LBF increase and the arterial blood pressure decrease were widely different. The lingual nerve-evoked change (i.e., fall) in arterial blood pressure showed a significant correlation with the contralateral LBF decrease, but not with the ipsilateral LBF increase. Prior administration of hexamethonium at 10 mg/kg markedly reduced both the ipsilateral LBF increase and arterial blood pressure decrease, although it was more effective against the former than against the latter. Pretreatment with scopolamine (muscarinic-receptor antagonist, 0.1 mg/kg), phentolamine (alpha-adrenoceptor antagonist, 0.1 mg/kg), or propranolol (beta-adrenoceptor antagonist, 0.1 mg/kg) failed to affect either response. However, 1.0 mg/kg phentolamine significantly reduced both responses (P<0.05). These results indicate that, in the rabbit, the LN-evoked reflex increase in ipsilateral LBF is (a) largely independent of any concomitant arterial blood pressure change and (b) probably due to active vasodilatation mediated via parasympathetic mechanisms. In contrast, the evoked decrease in contralateral LBF was proportional to the decrease in arterial blood pressure, suggesting that the former was secondary to the latter.

Adrenergic alpha-Antagonists↗
PubMed2003

Michael addition of stannyl ketone enolate to alpha,beta-unsaturated esters catalyzed by tetrabutylammonium bromide and an ab initio theoretical study of the reaction course.

Michael addition of stannyl ketone enolates to alpha,beta-unsaturated esters was accomplished in the presence of a catalytic amount of tetrabutylammonium bromide (Bu(4)NBr). Other typical systems using lithium enolate or silyl enolate with catalysts (TiCl(4) or Bu(4)NF) failed to give the desired products. The bromide anion from Bu(4)NBr coordinates to the tin center in enolate to accelerate the conjugate addition where a five-coordinated tin species was generated. The coordination of the bromide anion significantly raises the HOMO level of tin enolate and enhances its nucleophilicity. The conjugate addition provides the intermediate Michael adduct, which has an ester enolate moiety, and the adduct immediately transforms to alpha-stannyl gamma-ketoester by keto-enol tautomerization. This step contributes to the stabilization of the product system and leads to a thermodynamically favorable reaction course. An ab initio calculation reveals that the activation energy in the reaction using the bromide anion is lower than that of the reaction without using it. The transition state in either reaction course has a linear structure, not a cyclic one. This system can be applied to a variety of tin enolates and alpha,beta-unsaturated carbonyls involving enoates, enones, and unsaturated amides.

Journal Article↗
PubMed2003

Enhancement of sensitivity to cisplatin by orobol is associated with increased mitochondrial cytochrome c release in human ovarian carcinoma cells.

OBJECTIVES: Based on our previous report showing that orobol, a potent phosphatidylinositol 4-kinase (PI4K) inhibitor, produced cisplatin (DDP) sensitivity, we have determined the mechanism of orobol-sensitization effect. METHODS AND RESULTS: Orobol produced >2-fold DDP sensitivity in human ovarian carcinoma 2008 cells and its DDP-resistant variant 2008/C13*5.25 cells (C13). Because orobol had no effect on conventional mechanisms such as DDP accumulation or cellular metallothionein and glutathione content, we have focused on the apoptotic signaling pathway. Orobol induced a significant increase in apoptosis in DDP-treated cells, as estimated by frequency of condensed nuclear chromatin with Hoechst 33342 stain, although orobol alone did not have any effect on apoptotic potential. The caspase-3-inhibiting peptide Ac-DEVD-CHO completely inhibited the orobol sensitization effect but did not block DDP cell cytotoxicity per se. Orobol rendered both of these cells resistant to rhodamine 123 (Rh) by more than 2.5-fold, indicating significant decrease of mitochondrial membrane potential (DeltaPsim). Confocal laser microscopy of cells stained with the mitochondria (MT)-specific dye Rh revealed that orobol decreased Rh-fluorescent intensity. Electron microscopy of these cells showed that orobol induced swelling and condensation of MT. Orobol suppressed both naturally expressed and the DDP-induced Bcl-2 expression significantly. Orobol and DDP treatment reduced cytochrome c level in MT determined by Western blot analysis, indicating increased amount of cytochrome c release from MT, whereas orobol alone did not alter the amount of cytochrome c in MT. CONCLUSIONS: These results indicate that orobol produced DDP sensitivity in human ovarian carcinoma cells by inducing apoptosis through the MT-dependent signaling pathway.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Direct conversion of carbonyl compounds into organic halides: indium(III) hydroxide-catalyzed deoxygenative halogenation using chlorodimethylsilane.

The reaction of carbonyls and chlorodimethylsilane was effectively catalyzed by indium(III) hydroxide and afforded the corresponding deoxygenative chlorination products, in which the carbonyl carbon accepted two nucleophiles (H and Cl) with releasing oxygen. Only In(OH)3 catalyzed the reaction, and typical Lewis acids such as TiCl4, AlCl3, and BF3.OEt2 showed no catalytic activity. The reaction mechanism of this deoxygenative chlorination includes initial hydrosilylation followed by chlorination. Other nucleophiles such as allyl or iodine were available for this methodology. The moderate Lewis acidity of indium catalyst enabled chemoselective reaction, and therefore ester, nitro, cyano, or halogen groups were not affected during the reaction course.

Journal Article↗