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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 811 records · Page 45Linked to original sources

[Evaluation of genotoxicity by DNA damages].

A great number of genotoxins are known to be present in the environment. These genotoxins induce many kinds of DNA damage, and may cause changes in genetic information and cancer. Therefore, evaluation of such DNA damage is important to keep genetic information stable and to prevent cancer. We reviewed here methods used to assay the damage and the importance of this DNA damage in mutation. DNA damage is categorized into two groups, strand breaks and base modifications. To assay DNA strand breaks, the alkaline elution method, pulsed-field gel electrophoresis and single-cell gel assay are being used. The alkaline elution method determines both single- and double-strand breaks sensitively and quantitatively. Pulsed-field gel electrophoresis preferentially determines double-strand breaks, and the results of the method appeal to the eye as an electrophoretogram. The single-cell gel assay could determine both single- and double-strand breaks even in a single cell, and could evaluate susceptibility to the damage in individual cells. To assay base modifications, methods to detect differences in the physicochemical properties of the damage (physicochemical methods), immunoassays and the 32P-postlabeling method are being used. Physicochemical methods are suitable for chemically minor and abundant modifications such as those in 8-hydroxyguanine, using high-performance liquid chromatography or gas chromatography/mass spectroscopy. Immunoassays, by the use of specific antibodies against DNA damage, are highly sensitive to DNA damage such as changes in O6-methylguanine and thymine glycol, and simple once the assay systems have been established.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Schwannoma of the duodenum causing melena.

A rare case of duodenal schwannoma is reported. A 69-year-old man was admitted for evaluation of melena. Endoscopy and hypotonic duodenography showed a submucosal tumor in the third part of the duodenum. Biopsy findings were suggestive of leiomyosarcoma, therefore pancreatoduodenectomy was performed. Hematoxylin-eosin staining of the resected specimen showed interlacing bundles of spindle-shaped cells with palisading nuclei. Immunohistochemical staining showed positivity for S-100 protein and neuron-specific enolase, but desmin was negative, thus a diagnosis of schwannoma was made. Schwannoma is often difficult to distinguish from leiomyogenic tumors by standard staining, but immunohistochemical staining proved useful in this case.

Aged↗

Suppression of splenic enzyme activities by administration of aminopeptidase N (CD13) inhibitors: relationship between actions in vivo and in vitro.

The enzymatic changes in murine spleen caused by the administration for 20 successive days of various inhibitors of aminopeptidase N (leucocyte antigen CD13) have been compared. When compared with the control (saline), most of the inhibitors significantly suppressed splenic enzyme activities including those of ectoenzymes. A multivariate study indicated that the in vivo effects of the inhibitors were closely related to their inhibitory actions in vitro.

Amino Acids↗

Totally synthetic analogues of siastatin B. III. Trifluoroacetamide analogues having inhibitory activity for tumor metastasis.

A trifluoroacetamide analogue of siastatin B, (3S,4S,5R,6R)-6-(trifluoroacetamido)-4,5-dihydroxy-3-piperidine carboxylic acid has been chemically synthesized. This compound, as well as the previously synthesized analogue, (3R,4R,5R,6R)-6-(trifluoroacetamido)-3,4,5-trihydroxy-3-piperid inecarboxylic acid, showed marked inhibitory activity against beta-glucuronidase and significant inhibition of experimental pulmonary metastasis of the highly metastatic melanoma B16.

Acetamides↗

The novel immunostimulant N-563, an analogue of deoxyspergualin, promotes resistance to Candida albicans infection in mice.

An analogue of deoxyspergualin, N-563 has an immunostimulating activity whereas the mother compound has been found to be a potent immunosuppressant. In this study, the protective effect of the analogue against C. albicans infection was investigated in normal and immunosuppressed mice. In normal mice, N-563 treatment at 10 mg/kg for 3 days prior to infection significantly prolonged the survival time. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, N-563 at 3 and 10 mg/kg for 3 days prior to infection also significantly prolonged the survival time of mice. In addition, it augmented the phagocytic activity of neutrophils and enhanced the delayed type hypersensitivity reaction against C. albicans. Coincidentally, N-563 appeared to protect against secondary infection with C. albicans in the delayed type hypersensitivity-positive mice.

Adjuvants, Immunologic↗

Effect of conagenin on thrombocytopenia induced by antitumor agents in mice.

The effect of conagenin (CNG) on myelosuppression induced by antitumor agents was investigated. The daily administration of CNG prevented reduction in the number of platelets (PLT) observed in peripheral blood of mice given mitomycin C (10 mg/kg) but did not prevent reduction in the number of leukocytes (WBC). The effect on PLT was also confirmed in mice given cyclophosphamide (100 mg/kg). In mice given repeated doses of 5-fluorouracil (10 mg/kg), CNG prevented the reduction of PLT as well as WBC and maintained them at normal levels. CNG prevented reduction of the production of interleukin-2, 3 and 6 in cultured supernatants of spleen cells taken from mice given 5-fluorouracil. These results suggest that CNG modulates production of lymphokines which are responsible for thrombopoiesis.

Animals↗

Kinetic studies of the interaction between spergualin or 15-deoxyspergualin and amine oxidase from bovine plasma.

Spergualin (SG) and 15-deoxyspergualin (DSG) are derivatives of spermidine. Their substrate and inhibitor activities toward amine oxidase from bovine plasma were determined. SG was a good substrate of amine oxidase next to spermidine. The Km and Vmax for SG were 46.5 microM and 0.429 microM/minute, respectively, whereas the Km and Vmax for spermidine were 111 microM and 3.75 microM/minute, respectively. Thus SG has about two-fold stronger affinity to amine oxidase than spermidine, but its catalysis rate was one ninth of spermidine. In contrast, DSG was hardly oxidized and inhibited spermidine oxidation at low concentration. Affinity of both compounds for amine oxidase was determined by inhibition kinetics using benzylamine as substrate. SG and DSG competitively inhibited amine oxidase activity showing the Ki values of 175 microM and 7.46 microM, respectively.

Amine Oxidase (Copper-Containing)↗

Novel antibiotics, amythiamicins. II. Structure elucidation of amythiamicin D.

The structure of a unique polythiazole-containing cyclic peptide antibiotic, amythiamicin D, was elucidated by chemical degradations and NMR spectral analyses. Acid hydrolysis of amythiamicin D gave one mole of glycine and three new amino acids. Structures of N-acetyl-O-methyl derivatives of these new amino acids were determined by NMR and UV spectral analyses. Connectivities of these amino acids were determined by HMBC experiments.

Acetylation↗

Novel antibiotics, amythiamicins. III. Structure elucidations of amythiamicins A, B and C.

The structures of novel antimicrobial antibiotics, amythiamicins A, B and C, were elucidated by chemical degradations and NMR spectral analyses. The main frame from C-1 to C-41 of these antibiotics was the same as that of amythiamicin D. Amino acid autoanalyses of amythiamicins A, B and C showed that these have another one mole of serine and proline in comparison with amythiamicin D. Stereochemistries of both amino acids were determined to be L by chiral HPLC. These seryl-prolyl residues in amythiamicins A, B and C are attached at C-41 through an oxazoline ring, amide and ester bond, respectively.

Anti-Bacterial Agents↗

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties.

A new antibiotic, aldecalmycin, has been discovered in the culture broth of Streptomyces sp. MJ147-72F6. Aldecalmycin was purified by solvent extraction, Diaion HP-20 chromatography, silica gel chromatography, Sephadex LH-20 chromatography, HPLC and centrifugal partition chromatography. The 1H and 13C NMR spectra of aldecalmycin showed the presence of keto-enol tautomers. Aldecalmycin is equipotent in inhibiting the growth of sensitive and methicillin-resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. II. Structure elucidation by NMR studies.

A new antibiotic, aldecalmycin (1) was isolated from the culture broth of Streptomyces sp. MJ147-72F6. The 1H and 13C NMR spectra of 1 were complicated due to the presence of a beta-ketoaldehyde moiety. Therefore, 1 was converted into an ethylene ketal derivative (2) and into a dihydroaldecalmycin (3). These derivatives gave assignable NMR spectra. The planar structure was elucidated by using 1H-1H COSY, 2D-HOHAHA, 1H-13C COSY and HMBC spectra of 2. The conformation of the decalin ring was elucidated by using ID-HOHAHA, NOE difference and NOESY spectra of 3. The geometry of double bond in the side chain was determined by NOE difference and NOESY spectra of 3.

Anti-Bacterial Agents↗

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. III. Determination of absolute configuration.

The planar structure of aldecalmycin (1) had been determined in the previous paper, together with the conformations of the substituted trans decalin ring having one double bond and the sugar: beta-glucopyranoside type. The absolute configuration of 1 was a following problem to be solved. X-Ray crystallographic analysis of crystalline 4'-6'-O-benzylidenedihydroaldecalmycin (4) revealed the relative configuration. On the other hand, the stereoisomerism of the sugar was determined to be D by the optical rotation value of tetra-O-acetyl-alpha-methylglucopyranoside derived from 1. These results established the absolute configuration of 1.

Anti-Bacterial Agents↗

Biosynthesis of antitumor antibiotic, cytogenin.

The biosynthesis of antitumor antibiotic cytogenin, 3-hydroxymethyl-6-methoxy-8-hydroxy-isocoumarin, was studied by feeding 14C- or 13C-labeled compounds to culture of the producing organism, Streptoverticillium eurocidicum MI43-37F11. 14C-Acetate and 14C-methionine were efficiently incorporated into cytogenin as precursors. 13C NMR studies proved that the carbon skeleton of cytogenin is derived from pentaketide intermediate due to head-to-tail condensation of five acetate units and methyl group of 6-OCH3 is derived from methionine. It was suggested that 3-hydroxymethyl and/or 6-methoxy group of cytogenin were metabolized by hydroxylation and/or methylation from three intermediates.

Acetates↗

Antitumor effect of piericidin B1 N-oxide.

Piericidin B1 N-oxide was isolated from a culture broth of Streptomyces sp. as a novel inhibitor of phosphatidylinositol (PI) turnover. Piericidin B1 N-oxide specifically inhibited orthophosphate labeling of PI induced by epidermal growth factor (EGF) without affecting the formation of phosphatidic acid (PA). Like piericidins A1 and B1, piericidin B1 N-oxide inhibited ATP synthesis in A431 cells; however, the effect of piericidin B1 N-oxide on PI synthesis was stronger than that of piericidins A1 and B1. At the concentration inhibiting PI synthesis, piericidin B1 N-oxide showed no inhibitory effect on DNA, RNA, or protein synthesis. We also demonstrated that piericidin B1 N-oxide reversibly inhibited the growth of A431 cells in situ and suppressed the growth of Ehrlich carcinoma in vivo when administered to mice by intraperitoneal (ip) injection.

Adenosine Triphosphate↗

Cytostatin, a novel inhibitor of cell adhesion to components of extracellular matrix produced by Streptomyces sp. MJ654-NF4. I. Taxonomy, fermentation, isolation and biological activities.

Cytostatin has been identified as a novel inhibitor of cell adhesion to components of extracellular matrix (ECM) in cultured broth of Streptomyces sp. MJ654-NF4. Though cytostatin did not inhibit EL-4 cell adhesion to ECM components such as laminin and fibronectin; it inhibited the adhesion of B16 melanoma cells to laminin and collagen type IV but not to fibronectin. It exhibited antimetastatic activity on B16 melanoma cells in mice. The cytotoxicity of cytostatin are also reported.

Animals↗