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Biomedical subjects

N Otake

Publications and source records attributed to N Otake.

At least 19 recordsLinked to original sources
PubMed1992

Eruptive lichen planus.

We herein report a case of a rare variety of the acute eruptive form of lichen planus. The patient was a 51-year-old male who developed an intensely pruritic eruption on the lower legs which spread rapidly to all four extremities and trunk within a few months. The papulosquamous lesions were more than ten thousand in number. Topical steroid, cyclosporine, and systemic griseofulvin treatments were ineffective. However, there was a dramatic response to oral etretinate.

Etretinate↗
PubMed1992

Synthesis and antitumor activity of 4'-O-acylanthracyclines.

4'-O-Acyl derivatives of doxorubicin, daunorubicin, 13-deoxocarminomycin, 13-deoxo-10-hydroxycarminomycin, 13-deoxo-11-deoxycarminomycin were synthesized through the formation and mild acid hydrolysis of 2-oxazoline intermediates. The antitumor activity of these 4'-O-acyl derivatives against P388 leukemia was similar to or more effective than the parent anthracyclines.

Animals↗
PubMed1991

Determination of the new morpholino anthracycline MX2.HCl and its metabolites in biological samples by high-performance liquid chromatography.

Methods for determining concentrations of a new morpholino anthracycline MX2.HCl and its metabolites in biological samples using reversed-phase high-performance liquid chromatography and fluorescence detection are described. The limits of detection were less than 1 ng/ml for all compounds after extraction from 0.5 ml of plasma using C18 Sep-Pak cartridges and consecutive solvent extraction. The recoveries from rat plasma ranged from 72.0 to 89.3%. The peak-height ratio of the fluorescence intensities of these compounds versus internal standard showed a linear correlation for concentrations up to at least 500 ng/ml in the plasma (correlation coefficient r greater than 0.999). The within-day and between-day precisions of this assay were in the range 0.8-8.7% (n = 5) and 2.0-3.5% (n = 5), respectively. The concentrations of these compounds in the blood and urine can be also determined by a slight modification of the extraction procedure.

Animals↗
PubMed1991

Cellular pharmacology of MX2, a new morpholino anthracycline, in human pleiotropic drug-resistant cells.

We previously reported that MX2, a new morpholino anthracycline, showed marked effects on pleiotropic drug-resistant sublines of murine P388 leukemia in vivo as well as in vitro. In this study we examine the in vitro cytotoxicity against pleiotropic drug-resistant sublines of human tumor cell lines. MX2 was effective against multidrug-resistant sublines of four human tumor cell lines; these cells, having a 4.8- to 200-fold cross-resistance to Adriamycin (ADM) showed only a 0.7- to 2.3-fold resistance to MX2 compared with the sensitive cells. To elucidate the mechanism by which MX2 overcomes multidrug resistance, the intracellular pharmacology of MX2 in human myelogenous leukemia K562 and its ADM-resistant subline (K562/ADM) was examined. Both K562 and K562/ADM cells accumulated MX2 more easily than ADM, and the intracellular accumulation of MX2 attained a steady state in both cell lines within 30 min of incubation at 37 degrees C. The amount of MX2 that accumulated in K562/ADM at a steady state was only 1.3 times lower than that in K562. However, ADM was accumulated slowly in both cell lines compared with MX2, and the intercellular concentration reached a steady state in K562/ADM after 90 min of incubation and in K562 after more than 120 min. K562/ADM cells accumulated a 3.3-fold lower concentration of ADM than K562 after 120 min of exposure. The steady-state concentration of ADM in K562/ADM was 8.3 times lower than that of MX2. In addition, greater than 70% of MX2 was retained in both cell lines after 150 min of incubation in the absence of this drug. Verapamil, a calcium antagonist, hardly augmented the cytotoxicity of MX2 against K562/ADM, and no distinct effect of this drug on both the time course and the maximal level of accumulation of MX2 was observed. Interestingly, MX2 effectively inhibited ATP/Mg2(+)-dependent [3H]vincristine binding to K562/ADM membrane preparations, indicating that MX2 could be transported outside the cell by an active efflux pump. The high intracellular accumulation and retention of MX2 in K562/ADM through the rapid influx of the drug into the cells may be one of the reasons why MX2 circumvents pleiotropic drug resistance.

Antibiotics, Antineoplastic↗
PubMed1990

Molecular cloning and characterization of the gene conferring curromycin resistance on a curromycin non-producing mutant derived from Streptomyces hygroscopicus 358AV2.

We cloned six different DNA fragments from a curromycin producing strain, Streptomyces hygroscopicus 358AV2, which confer curromycin-resistance on a curromycin non-producing and sensitive strain, S. hygroscopicus Rgll, a protoplast regenerant of the strain 358AV2. We studied the plasmid pSHR2 carrying one of the DNA fragments. By Southern blot analysis, the cloned DNA sequence in pSHR2 was found to be deleted in the Rgll genome. From the Rgll strain, a curromycin producing revertant A-4 was obtained, indicating that the structural genes for the curromycin biosynthesis and resistance are retained in the Rgll genome. Based on the existence of A-4 and the deletion of the DNA region corresponding to the cloned DNA sequence in the Rgll genome, we conclude that the cloned DNA sequence carries a regulatory gene governing curromycin-resistance but not the resistance gene itself. The smallest DNA region in pSHR2 conferring curromycin-resistance was sequenced, and it was found that there were two small open reading frames (ORF) on each strand of the cloned DNA. In-frame fusion of ORFs to the reporter gene lacZ revealed that one ORF designated cre was indeed translated in vivo. The putative gene product deduced from the cre ORF is a basic and hydrophilic protein having a calculated molecular weight of 6 kdaltons.

Amino Acid Sequence↗
PubMed1978

Studies on the ionophorous antibiotics. XV The monovalent cation selective ionophorous activities of carriomycin, lonomycin and etheromycin.

The cations selectivity profiles of the carboxylic ionophores, carriomycin, lonomycin and etheromycin, have been investigated by measuring the complexation affinities for metal cations and the cation transport activity through an organic barrier. In a two-phase partition study, carriomycin and lonomycin formed complexes more readily with K+ than with NH4+, Rb+ or Na+, but not with Li+ or Cs+. On the other hand, etheromycin exhibited a great preference for K+ or NH4+ over Na+, Li+ or Rb+, but displayed no binding affinity for Cs+. The alklaine degradation product of lonomycin exhibited a preference for K+ or Na+, but its complexation affinities were much lower than those of the parent compound. Carriomycin, lonomycin and etheromycin efficiently transported K+, Rb+ and Na+ through a CCl4 barrier. But did not carry Ca2+. These antibiotics caused a massive release of K+, Rb+ or Na+, but not of Li+ and Cs+, from mitochondria previously loaded with these cations by valinomycin or monazomycin. Thus, it is concluded that carriomycin, lonomycin and etheromycin are monovalent cation selective ionophores.

Animals↗
PubMed1978

Studies on the ionophorous antibiotics. XVI. The ionophore-mediated calcium transport and concomitant osmotic swelling of mitochondria.

The effects of various carboxylic ionophores on divalent metal cation translocation in mitochondria have been investigated. High levels of divalent cation ionophores lysocellin and lasalocid A (10 approximately 50 micrometer) produced mitochondrial osmotic swelling in Ca2+ or Mg2+ medium, which was associated with an increase of cation influx. The extent of swelling was a function of both the ionophore and cation concentrations in the medium. This effect was larger in mitochondria de-energized by treatment with antimycin A and oligomycin than in respiring mitochondria. On the other hand, the monovalent cation ionophores carriomycin and etheromycin at concentrations of 50 approximately 100 micrometer also induced mitochondrial swelling in Ca2+ medium but were ineffective in Mg2+ medium. Addition of ruthenium red reversed divalent cation ionophore-induced swelling and released Ca2+ from preloaded mitochondria. In contrast, ruthenium red increased monovalent cation ionophore-induced swelling. In a divalent cation-free medium, lysocellin and lasalocid A caused depletion of membrane-bound Ca2+ and released endogenous Ca2+ and Mg2+ from mitochondria, while carriomycin and etheromycin exerted only a limited effect. These results indicate that the divalent cation ionophores affect divalent cation distribution in mitochondria by increasing both influx and efflux of the cations through the inner membrane.

Animals↗