Isolation and structure determination of a novel phosphatidylinositol turnover inhibitor, piericidin B1 N-oxide.
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Biomedical subjects
Publications and source records attributed to N Matsuda.
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A new antibiotic, dioxamycin (1) was isolated from the culture broth of the strain MH406-SF1, which was closely related to Streptomyces xantholiticus. This antibiotic was purified by countercurrent chromatography, column chromatography and preparative HPLC. The molecular formula of 1 was determined to be C38H40O15 by HRFAB-MS. The structure was determined by spectral analysis of 2D NMR; 1H-1H COSY, 13C-1H COSY, long range 13C-1H COSY (HMBC) and NOESY. The antibiotic is active in vitro against Gram-positive bacteria and some tumor cells. Dioxamycin is a benz[a]anthraquinone antibiotic related to capoamycin.
Leuhistin has been isolated from the culture broth of Bacillus laterosporus BMI156-14F1 as part of a program designed to find microorganism-produced inhibitors of aminopeptidase M (AP-M). It was purified by use of column chromatography on Sepabeads SP206, Amberlite IRC-50, MCI gel CHP-20P and Sephadex G-10 and then isolated as colorless needles. Leuhistin inhibits AP-M strongly and it also inhibits AP-A and AP-B weakly. It is competitive with the substrate, and the inhibition constant (Ki) was 2.3 x 10(-7) M.
Methods of computer-assisted diagnosis based on laboratory data are divided into so called rule-base system in which the diagnostic knowledge of physicians is programmed and those using multivariate analysis and mathematical models such as fuzzy interference. In this report, the principles and the technique of matrix discrimination method, which belongs to the latter group, are described, and its usefulness in clinical diagnosis evaluated. By the present method, subjects (diseases) are separated from two or more groups of subjects (diseases) to be discriminated on the basis of laboratory data. The method, based on the linear discrimination analysis, is characterized by optimization of selection of subjects to be discriminated and selection of test items and inference by the use of a discrimination curve. When this method was applied to discrimination of healthy individuals and patients with various liver and biliary disorders (11 diseases), all healthy individuals were discriminated from the patients. A mean of 97.0% of patients with hepatic parenchymal disorders were found in the top two, and 86.2% of those with space-occupying diseases in the top three, of the 12 diseases from which the disease of each patient was to be estimated. This diagnostic ability of the matrix discrimination method far exceeded the physicians' expectations.
A theory of laboratory data-based diagnosis and results of its application are reported. The diagnosis was made by linear discriminant analysis and matrix analysis, and the two diagnostic modalities were tested in healthy subjects and patients with 10 different diseases of the liver and the biliary tract. The optimal number of test items to be incorporated in the discriminant for screening was 2 to 3 in liver parenchymal diseases but tended to be 4 to 5 or more in obstructive or space-occupying diseases. A newly designed matrix discrimination was applied to this evaluation. By this method, all healthy individuals could be discriminated from patients. A mean percentage of 97.5% (92-100%) of patients with liver parenchymal diseases could be discriminated by the first 2 variables, and a mean of 86.2% (71-98%) of those with obstructive or space-occupying diseases could be discriminated by the first 3 variables. The basic architecture and function of a quantitative diagnostic system for screening of diseases of the liver and the biliary tract, which we are developing on the basis of this matrix discrimination method, are outlined with our prospects of computer-assisted laboratory diagnosis.
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We present studies for development of an enzymatic diagnostic method for periodontitis. A rapid and sensitive diagnostic method named SK-013 was provided by Sunstar Inc. to evaluate the peptidase activities specifically derived from periodontopathic bacteria such as Bacteroides gingivalis, Bacteroides forsythus and Treponema denticola and some strains of Capnocytophaga species. The results obtained indicated the specificity of the enzymatic reaction in this system.
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To assist the physician in the clinical decision making process, the CALD (computer-assisted laboratory diagnosis) system was constructed. This was serially connected with a multi-center laboratory information system for practical use. From among the examples of CALD used, a diagnostic system for the blood spectrum and peripheral hemogram was selected for the evaluation of the principle and usefulness, and for a discussion of further problems. The method of selection of suitable tests for hepatobiliary disease screening (from a normal group and 10 groups of other diseases) and its diagnostic logic and usefulness of quantitative diagnosis using a discriminant curve were then discussed. The optimal combinations were most often found to involve 1-5 tests. Near maximal diagnostic efficiency was achieved by 50-100 combinations. The diagnostic efficiency of the optimal test was higher than expected, with a range of 80-100% (92.7% on average).
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A rare case of malignant acanthosis nigricans associated with lung cancer is presented. The case involved a 70-year-old man who had oral changes and various immunologic dysfunctions, including an increase in antinuclear antibodies. Oral lesions were characterized by papillary hyperplasia, formation of grooves, pigmentation of the upper lip and cheeks, and a loss of taste sensation. After the patient's lung cancer was treated with anticancer drugs, the histopathologic examination showed a marked improvement in oral lesions and significant normalization of immunologic abnormalities. The present case provides unique evidence that oral lesions associated with acanthosis nigricans have a significant correlation with lung cancer and high titers of antinuclear antibodies.
The characteristics of the specific bindings of [3H]nitrendipine (Nit) and [3H](+)PN200-110 (PN) to crude membranes from rat skeletal, cardiac, and uterine muscle and whole brain were investigated, with special interest in the effect of UV irradiation on these bindings. The specific bindings of [3H]Nit and [3H](+)PN to these crude membranes were saturable and reversible. The specific bindings of [3H]Nit to all these membranes except crude skeletal membranes was maximum in the presence of 0.15 M NaCl plus 1 mM CaCl2 and minimal in the absence of these ions, but the specific bindings of [3H](+)PN to these crude membranes was not affected significantly by these ions. A calcium agonist and antagonists inhibited the specific bindings of [3H]Nit and [3H](+)PN to these crude membranes, the order of their inhibitory effects on specific [3H]Nit bindings being roughly Nit greater than or equal to (+)PN greater than or equal to (-)PN much greater than Bay K 8644 (Bay) greater than verapamil (Ver) greater than diltiazem (Dil). In crude skeletal membranes only, PN caused significant stereospecific inhibition. The order of inhibitions of specific [3H](+)PN bindings to these crude membranes was generally (+)PN greater than Nit greater than or equal to (-)PN greater than Bay much greater than Ver greater than or equal to Dil. In all these crude membranes, UV irradiation completely prevented decrease in the amount of specific binding of [3H](+)PN binding on addition of excess unlabeled (+)PN. These findings suggested that [3H]Nit and [3H](+)PN bind to voltage-sensitive calcium channels in crude membranes from rat skeletal, cardiac, and uterine muscle and whole brain, and that UV irradiation changes the specific bindings of [3H]Nit and [3H](+)PN from reversible to irreversible bindings.
The characteristics of photoaffinity labeling with the calcium agonist [3H]Bay K 8644 (Bay) and the calcium antagonists [3H]nitrendipine (Nit) and (+)PN200-110 (PN) of crude membranes from rat skeletal, cardiac, ileal, and uterine muscles and whole brain were investigated. In all these crude membranes, [3H](+)PN (20 nM) was mainly photoincorporated into one protein band with a molecular weight of 30,000 - 41,000 Da. It was also incorporated into some other bands of all these crude membranes. The photoincorporation of [3H](+)PN into these crude membranes was inhibited by the presence of 20 microM unlabeled (+)PN. The photoincorporation of [3H](+)PN into these crude membranes depended on its dose and on the time of UV irradiation. No incorporation of [3H](+)PN was observed in the absence of UV irradiation. The incorporation was not affected by the presence of 1 mM CaCl2 and/or 0.15 M NaCl, but was significantly decreased by 20 microM (+)PN and slightly decreased by 20 microM (-)PN, 20 microM Bay, 1 mM diltiazem, or 1 mM verapamil. Namely, enantiomers of PN caused various extents of stereoselective inhibition of photoaffinity labeling by [3H](+)PN of specific protein bands in these crude membranes. [3H]Nit was photoincorporated into these crude membranes in the same way as [3H](+)PN, but [3H]Bay was not photoincorporated. However, 20 microM unlabeled Nit did not consistently inhibit photoaffinity labeling with [3H]Nit. These findings suggested that measurement of photoaffinity of crude membranes from rat skeletal, cardiac, and uterine muscles and whole brain with [3H](+)PN by UV irradiation is a useful method for investigating the characteristics of the voltage-dependent calcium channels that are affected by 1,4-dihydropyridine derivatives.
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