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Biomedical subjects

K Yazawa

Publications and source records attributed to K Yazawa.

At least 163 records · Page 9Linked to original sources

High resolution chromatography of ribonucleosides and its application to RNA analysis.

A simple and precise method was developed for the separation of nucleosides including modified nucleosides and oligonucleotides. Nineteen kinds of nucleosides were completely separated by HPLC using an ODS column (TSK-gel ODS 80TM) and aqueous mobile phases. The RNA molecule was digested by base restrictive RNase (RNase A, RNase T1) and the digests were separated chromatographically into each oligonucleotide. The nucleoside composition of an oligonucleotide was then determined by this analytical system. It is thus possible to fit the oligonucleotide in the original RNA molecule by using modified bases as markers. The reaction site of quinacrine mustard for tRNA(Phe) (from yeast) could be determined by this analytical system.

Base Sequence↗

Paecilotoxin production in clinical or terrestrial isolates of Paecilomyces lilacinus strains.

The production of paecilotoxin from various isolates of Paecilomyces lilacinus was studied using three different media and high performance liquid chromatography (HPLC). Alkaline medium was found to be suitable for the production of the toxins. Among 20 strains tested, 19 including four clinical isolates were found to produce the toxins. Production patterns of paecilotoxins were very similar in each strain and the main toxins were A and B.

Amino Acid Sequence↗

Multiple types of voltage-dependent Ca channels in mammalian intestinal smooth muscle cells.

(1) Whole-cell and single channel recording techniques have been applied to smooth muscle cells isolated from guinea-pig taenia coli to examine whether multiple types of Ca channels exist. (2) Whole-cell recordings under physiological Ca concentration (1.8 mM) revealed two current components with fast and slow inactivating kinetics. The fast inactivating component was present when cells were held at very negative potentials (-80 mV). It was insensitive to the dihydropyridine (DHP) derivative, nifedipine. In contrast, the slow inactivating component was present at less negative holding potentials. It was blocked by nifedipine. (3) The two current components were found to have closely similar voltage dependencies for activation. (4) These results suggest that the fast inactivating decay of the Ca current was mediated not only by the entry of Ca into the cell but also by a voltage-dependent process via a different type of Ca channel with fast inactivating kinetics. (5) Recordings from cell-attached membrane patches with 100 mM external Ba clearly showed the existence of multiple types of Ca channels with different conductances. (6) The large conductance channels (30 pS) activated at more positive potentials (0 mV) and their averaged current decayed much more slowly. The DHP Ca antagonist, nifedipine, inhibited the large conductance channels increasing the proportion of blank sweeps and reducing the averaged current. On the other hand, the DHP Ca-agonist, BayK 8644, increased the average current by increasing the mean open-times of the large conductance channels. The presence of micromolar Cd in the patch pipettes produced a flickering block of the large conductance channels.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

In-vitro activity of flomoxef, a new oxacephem group antibiotic, against Nocardia in comparison with other cephalosporins.

The susceptibility of 113 strains of pathogenic Nocardia, N. asteroides, N. farcinica, N. nova, N. brasiliensis and N. otitidiscaviarum to a new oxacephem antibiotic flomoxef was determined by an agar dilution method in comparison with those of 13 other cephalosporins. Flomoxef was two to 50 times more active against these pathogenic Nocardia than other cephalopsorins tested. However, there were differences in susceptibility to this antibiotic among these Nocardia strains. N. asteroides was the most sensitive species, followed by N. farcinica and N. nova. N. brasiliensis was moderately sensitive and N. otitidiscaviarum was resistant.

Cephalosporins↗

In vitro susceptibility of Nocardia spp. to a new fluoroquinolone, tosufloxacin (T-3262).

The in vitro activity of a new fluoroquinolone, tosufloxacin (T-3262), against 111 pathogenic Nocardia strains was studied by an agar dilution method and compared with the activities of other fluoroquinolones. All strains were susceptible to tosufloxacin, and the drug was 2 to 20 times more active than four other quinolones tested. Nocardia farcinica was the Nocardia species most susceptible to tosufloxacin.

4-Quinolones↗

Determination of catecholamines and their metabolites in adrenals of stress-loaded and wild suncus (Suncus murinus).

The contents of catecholamines and their metabolites were measured in the adrenals of 3 groups of suncus. The first group was naive housed suncus; the second, suncus with stress-loading; and the third, wild ones. There were no significant differences in dopamine, norepinephrine and normetanephrine levels among the control, stress and wild groups. The content of epinephrine, however, decreased in the stress and wild group to 57% and 18%, respectively. These results suggest that housed suncus can easily react to stressful circumstances.

Adrenal Glands↗

[In vitro susceptibility of pathogenic Nocardia to beta-lactam antibiotics, especially imipenem, a carbapenem antibiotic].

In vitro antibacterial activity of 30 beta-lactam antibiotics including 2 beta-lactamase inhibitors (clavulanic acid and sulbactam) against 2 major pathogenic Nocardia, i.e. Nocardia asteroides group and Nocardia brasiliensis was studied. Among the antibiotics tested, a newly developed carbapenem antibiotic, imipenem (IPM), was found to be the most active, followed by oxacephem group antibiotic flomoxef (FMOX). IPM exhibited activity against only N. asteroides group (N. asteroides, Nocardia farcinica and Nocardia nova). On the other hand, FMOX showed activity against all pathogenic Nocardia tested. A 2- to 30-fold decreases in minimum inhibitory concentration (MIC) for N. asteroides, N. brasiliensis and N. farcinica was noted when antibiotics and beta-lactamase inhibitors were combined compared to antibiotics alone. Further combination and enzymatic studies indicated that all pathogenic Nocardia possess beta-lactamase except for a half of the strains of N. nova. These species' specific sensitivity patterns of pathogenic Nocardia are discussed in this paper with references to their taxonomic positions.

Anti-Bacterial Agents↗

Production of eicosapentaenoic acid by marine bacteria.

About 5,000 strains of marine microorganisms were screened for eicosapentaenoic acid (EPA)-producing ability, which was detected in 88 of them. All of the latter were found to be obligate aerobic, Gram-negative, motile, short rod-shaped bacteria. One strain, designated as SCRC-8132, showed a doubling time of 30 min at 25 degrees C and produced 20 mg/liter (4 mg/g dry cells) when cultured in a P-Y-M-Glucose medium for 18 h. The EPA to total fatty acids ratio was 24%. The strain produced 26 mg EPA/liter (15 mg/g dry cells) when cultured at 4 degrees C for 5 days, the EPA ratio being increased to 40%.

Bacteria↗

Structural studies on minor components of saframycin group antibiotics saframycins F, G and H.

Three minor components of saframycin group antibiotics, saframycins F, G and H were isolated and their structures were determined by comparison with the spectral data of UV, IR, and 1H and 13C NMR of already reported saframycins A and D. Saframycins F, G and H were 21-cyanosaframycin D, 14-hydroxysaframycin A and 25-dihydro-25-beta-ketopropyl-saframycin A, respectively.

Anti-Bacterial Agents↗

Isolation and structural elucidation of new saframycins Y3, Yd-1, Yd-2, Ad-1, Y2b and Y2b-d.

A new series of saframycins Y3, Yd-1, Yd-2, Ad-1, Y2b and Y2b-d was produced by directed biosynthesis employing resting cells of saframycin producer, Streptomyces lavendulae No. 314. Their structures were determined by comparison with the spectral data of UV, IR, and 1H and 13C NMR of saframycin A, whose structure has already been established. Saframycin Y3 is 25-deoxy-25-aminosaframycin A, while saframycin Yd-1 is 26-homosaframycin Y3, and saframycin Y2b is a dimer of saframycin Y3. Saframycin Ad-1 is 26-homosaframycin A. Saframycin Yd-2 is 26-demethylsaframycin Y3, and saframycin Y2b-d is a dimer of saframycin Yd-1.

Anti-Bacterial Agents↗

Antitumor activity of new semisynthetic saframycin derivatives.

Saframycins Yd-1 and Y3, which have an amino functional group in the side chain, were recently obtained by a directed biosynthesis. Twenty-eight side chain-modified chemical derivatives were prepared from these saframycins, and their in vitro and in vivo antitumor activities were studied. Among these new derivatives, three saframycins, namely, two N-acyl derivatives, pivaloyl- and n-caproylsaframycin Y3, and one water-soluble type, saframycin Yd-1.HCl, were found to show marked antitumor activity against L1210 mouse leukemia cells. Further studies of these saframycin derivatives using B16-F10 melanoma and Lewis lung carcinoma indicated that all three saframycins are also active against B16-F10 melanoma; saframycin Yd-1.HCl showed the greatest prolongation of survival time. Marked inhibition of spontaneous metastasis of Lewis lung carcinoma was observed in mice treated with these new derivatives. Structure-activity relationships among these semisynthetic saframycins are discussed.

Animals↗

Biosynthetic studies on saframycin A, a quinone antitumor antibiotic produced by Streptomyces lavendulae.

The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors. Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture. The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A. Feeding experiments with [1-13C]tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance. Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A.

Amino Acids↗

Directed biosynthesis of new saframycin derivatives with resting cells of Streptomyces lavendulae.

Saframycin A is an antitumor antibiotic produced by Streptomyces lavendulae 314 which falls into the category of the N-heterocyclic quinone group. Biosynthetically the quinone ring is derived from two tyrosine molecules which condense to generate the basic ring system of saframycin A. The side chain also has been found to derive from two amino acids, i.e., glycine and alanine. Supplementation by various amino acid analogs of the side chain produced three new saframycin derivatives with a replaced side chain. These three saframycins, designated Yd-1, Yd-2, and Y3, contained 2-amino-n-butyric acid, glycine, and alanine residues, respectively. in place of the normal N-terminal pyruvic acid in the side chain of saframycin A. Feeding experiments with 13C-labeled dipeptide indicated that the amino acids are probably incorporated in the side chain as a dipeptide unit. It was also found that saframycin A is produced from saframycin Y3 by an enzymatic deamination reaction. Based on these results, saframycin biosynthesis in S. lavendulae is discussed.

Amino Acids↗