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Biomedical subjects

A Yoshimoto

Publications and source records attributed to A Yoshimoto.

At least 55 records · Page 3Linked to original sources

New anthracycline antibiotics 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin.

Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomy-cin) and D788-3 (10-carboxy-11-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured L1210 leukemic cells. Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin.

Animals↗

Mechanism of antisense effect studied by functionalized oligonucleotides.

In order to study the mechanism of antisense effects, various functional groups such as photocrosslinkers, fluorescent materials, and gold particles were introduced to antisense DNAs. Upon UV-irradiation, the hybrid between DNA and antisense DNA with a photocrosslinker was stabilized. The fluorescence microscopy and transmission electron microscopy (TEM) represented clear images of antisense DNA in the cultured cells. Fluorescent-labeled S-Oligos were recognized in the cytoplasm and especially on certain organs, which are not specified. TEM images of cultured cells treated with gold-conjugated S-Oligo suggested the mechanism of cellular uptake of antisense DNA.

Base Sequence↗

Effect of interstimulus interval on perceived sensation and intradental nerve activity during thermal tooth stimulation in man.

The effect of interstimulus interval on nerve responses and subjective sensory ratings evoked by thermal stimulation of the teeth were studied in man. A total of 30 unitary discharges during heat stimulation of the lower incisor teeth were recorded from the inferior alveolar nerves using microneurographic technique. Fifteen of them had threshold sensory ratings above 3 (pain related-units) and 15 had ratings of less than 2 (non-pain-related units). Repetitive heat stimulation was applied to the teeth with interstimulus intervals of 180 s (ISI 180) and 30 s (ISI 30). Repetitive (ISI 180 and ISI 30) non-painful heat stimulation of the teeth did not alter either the intensity ratings or unitary discharge activities of non-pain-related units (P > 0.05). Repetitive painful heat stimulation of the teeth with ISI 180 did not alter the intensity ratings of pain-related units (P > 0.05), whereas that with ISI 30 significantly reduced the intensity ratings of pain-related units during a second session of heat trials (P < 0.05). On the other hand, repetitive heat stimulation of the teeth with ISI 180 caused a slight reduction in the firing frequency of pain-related units (P > 0.05). Repetitive painful heat stimulation with ISI 30 significantly reduced the firing frequency of pain-related units (P < 0.05).

Adult↗

[Comparison of duodenogastric reflux (DGR) to esophageal substitute between retro-sternal route and posterior mediastinal route].

To elucidate superiority of route among surgery of esophageal cancer with stomach tube, duodenogastric reflux (DGR) were examined in nine cases of retro-sternal bypass (RS) and 18 cases of posterior mediastinal group (PM) by means of questionnaire of reflux esophagitis, esophageal transit scintigram and 24 hour pH monitoring to those patients. Firstly, in order to readily compare the two groups, each section of reflux symptoms was expressed as a brief score by dividing each symptom into strength (0-3) and frequency (0-3). Mean score of reflux sensation was less in RS than in PM significantly (0.9 vs. 2.9, p < 0.01). The median value showed that patients in PM had much DGR symptoms than those in RS significantly (8.5 vs. 5.5, p < 0.01). In esophageal transit scintigram, TcO4- (85 MBq) was counted by gamma camera at the upper (ROI-1), center (ROI-2), and lower (ROI-3) sites of the sternum bone in the upright position. The descending time of RI peak from ROI-1 to ROI-3 in RS was shorter than PM (2.1 sec vs. 3.9 sec, N.S.). At ROI-2, clearance rate of RI in RS was similar to that in PM. At ROI-3, clearance rate of RI in RS was better than that in PM significantly (80.0% vs. 49.6%, p < 0.05). Scintigram revealed RI stasis in PM, which might be presumably concerned to DGR. Intragastric pH was measured continuously 5 and 15 cm below the esophagogastrostomy using 2-channeled antimony pH sensors.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenogastric Reflux↗

Characterization of the alternative oxidase protein in the yeast Hansenula anomala.

The cyanide-resistant respiratory pathway is induced by respiratory inhibitors in the yeast Hansenula anomala. A monoclonal antibody against the alternative oxidase in the higher plant Sauromatum guttatum cross-reacted with a 36-kDa mitochondrial protein induced by antimycin A in H. anomala and with a protein encoded by a cDNA which was previously cloned for an antimycin A-inducible mRNA in the yeast. There was a similarity in the amino acid sequence between the cDNA-encoded protein and the plant alternative oxidase protein. We propose that the 36-kDa mitochondrial protein encoded by the cDNA is a component of alternative oxidase in H. anomala.

Amino Acid Sequence↗

Microbial glycosidation of some anthracycline antibiotics by an antibiotic-negative mutant of aclarubicin producer.

Microbial conversion of anthracyclinone monosaccharides using aclarubicin-negative mutant of Streptomyces galilaeus was found to produce anthracyclinone disaccharides which had either rhodinose or 2-deoxyfucose as an additional sugar. By this conversion we obtained twelve new anthracyclines from seven anthracyclines which had rhodosamine, N-monomethyldaunosamine or daunosamine at C-7 as a glycosidic sugar. All products had a reduced cytotoxic activity in comparison with those of parent compounds. However, some of them showed a therapeutically improved antitumor effects against L1210 leukemia in vivo.

Aclarubicin↗

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. II. New anthracycline metabolites produced by a blocked mutant strain RPM-5.

A daunorubicin-blocked mutant strain RPM-5 derived from a new baumycin-producing Streptomyces sp. D788 accumulated a major precursor metabolite D788-1 (10-carboxyl-13-deoxocarminomycin) and nine minor metabolites in the culture broth. Five among them were new with a substituent at C-10 or the altered side chains at C-9. Isolation, purification and identification of all anthracycline metabolites produced by strain RPM-5 are described with their antitumor activities against L1210 cells.

Animals↗

Possible involvement of superoxide anion in the induction of cyanide-resistant respiration in Hansenula anomala.

A chemiluminescence study showed that Qi site inhibitors such as antimycin A induce O2- generation in respiring cyanide-sensitive mitochondria from the yeast, Hansenula anomala. The O2- generation was suppressed by radical scavengers such as flavone, butylated hydroxyanisole, and Co0. Induction of cyanide-resistant respiration in H. anomala cells by Qi site inhibitors was also inhibited by these radical scavengers. Furthermore, antimycin A-induced synthesis of the mitochondrial 36-kDa protein, which is thought to be the alternative oxidase functional in the cyanide-resistant respiratory pathway, was abolished by the addition of flavone. These observations suggest that O2- is somehow involved in the induction of cyanide-resistant respiration.

Anions↗

Anti-erythrocyte membrane antibodies detected in sera of dogs naturally infected with Babesia gibsoni.

Due to the potential for anti-erythrocyte membrane antibodies as possible enhancers of erythrocyte destruction, the presence of serum anti-erythrocyte membrane antibodies in 31 dogs with Babesia gibsoni infection admitted to a veterinary hospital was investigated by an enzyme linked immunosorbent assay (ELISA) and immunoblotting analyses. This infection resulted in an increase of anti-erythrocyte membrane antibodies in 84% (IgG) and 74% (IgM) of 31 infected dogs, respectively. This was confirmed by the similarity in the protein profiles of the erythrocyte membrane antigens immunoblotted with rabbit antiserum to dog erythrocyte membrane antigens and infected dog serum. These results suggest the production of anti-erythrocyte membrane antibodies was induced by B. gibsoni infection.

Anemia↗

Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. I. Isolation of antibiotic-blocked mutants and their characterization.

Biosynthetically blocked mutants were obtained from a baumycin-producing Streptomyces sp. D788 newly isolated from soil. The first mutant isolated was a baumycin-negative but daunorubicin-accumulating mutant with a loss of 4'-substitution activity, from which all other blocked mutants were successively derived. These included a known 11-deoxydaunorubicin-producing mutant and several new types of mutants which produced mainly 10-carboxy-13-deoxocarminomycin, 10-methoxycarbonyl-13-deoxocarminomycin, their 11-deoxy derivatives or a precursor aglycone, respectively. In this paper, all the anthracycline components produced by the parent strain and its two known blocked mutants, a daunorubicin producer and a 11-deoxydaunorubicin producer, are also determined by HPLC and five new components are isolated. Cytotoxicities in vitro of all the components against L1210 cell culture are also described.

Animals↗

Production of new anthracycline antibiotics 1-hydroxy-oxaunomycin and 6-deoxyoxaunomycin by limited biosynthetic conversion using a daunorubicin-negative mutant.

A limited biosynthetic conversion of some known anthracyclinones using a specific daunorubicin-nonproducing mutant provided four new anthracycline antibiotics: 1-Hydroxy-10-methoxycarbonyl-13-deoxocarminomycin; 1-hydroxy-13-deoxocarminomycin; 1-hydroxyoxaunomycin and 6-deoxyoxaunomycin. Their isolation and purification from bioconversion broth, structural determination and antitumor activities against leukemic L1210 cells are described.

Animals↗

Photochemically obtained N-demethyl derivatives of anthracyclines.

New N-monodemethyl and N-didemethyl derivatives were obtained from seven N-dimethylamino sugar (rhodosamine)-containing anthracyclines by photochemical reaction and their in vitro bioactivities against L1210 cell culture were compared with those of their N-dimethyl parent compounds. N-Demethyl derivatives obtained from betaclamycin T (7-O-rhodosaminyl-beta-rhodomycinone) were much more cytotoxic while those from the other six antibiotics were rather less active as compared with their parent compounds. The N-demethylation also gave a considerably greater decrease in the inhibitory activity on RNA synthesis as compared to DNA synthesis, so that the N-demethyl derivatives showed smaller IC50 ratios on DNA/RNA than their parent compounds.

Animals↗

Production of new anthracycline antibiotics by microbial 4-O-methylation using a specific daunorubicin-negative mutant.

Microbial 4-O-methylation using a specific daunorubicin-blocked, nonproducing mutant provided the new anthracycline antibiotics 4-O-methylbetaclamycin T, 4-O-methylyellamycin A and 4-O-methyl-13-hydroxyoxaunomycin, from which 4-O-methyloxaunomycin and 4-O-methyl-6-deoxyoxaunomycin were then prepared by further photochemical N-demethylation. Antitumor activities in vitro and in vivo against L1210 cells were compared with those of their 4-O-demethyl derivatives. It was found that all the 4-O-methyl derivatives had a markedly reduced cytotoxicity in vitro as compared with the 4-O-demethyl compounds. However, some of them were endowed with a significantly improved antitumor activity in vivo.

Animals↗

Molecular cloning of cDNA for antimycin A-inducible mRNA and its role in cyanide-resistant respiration in Hansenula anomala.

A cDNA for mRNA induced by antimycin A in Hansenula anomala was cloned. The mRNA for the cDNA was expressed in the yeast under the conditions expressing the cyanide-resistant respiration activity. The nucleotide sequence revealed a long open reading frame of 342 codons encoding a protein with a molecular weight of 40,282 in the cDNA. An antibody recognizing the protein encoded by the open reading frame was produced. Immunoblotting of H. anomala proteins with this antibody showed that a 36 kDa protein localized in mitochondria was a mature form of the protein encoded by the cDNA. It is suggested that the cloned cDNA encodes a protein involved in the cyanide-resistant respiratory pathway.

Amino Acid Sequence↗

Anthracycline metabolites from Streptomyces violaceus A262. I. Isolation of antibiotic-blocked mutants from Streptomyces violaceus A262.

Five mutant (or variant) strains producing new anthracycline antibiotics were derived from Streptomyces violaceus A262 by mutagenesis treatment. Strain SE1-625 showed a limited production of three known beta-rhodomycinone diglycosides while the parent strain produced numerous unidentified beta-rhodomycinone glycosides. Strain SU2-730 was an antibiotic-blocked mutant which produced only epsilon-rhodomycinone glycosides (named epelmycins). Strains SC-7 and SE2-2385 were variants which produced alpha-citromycinone glycosides (named yellamycins) and beta-isorhodomycinone glycosides (named obelmycins), respectively. Strain SE2-2385-A1 produced alpha 2-rhodomycinone glycosides (named alldimycins). Glycosidation-less mutants which accumulated only aglycone were also obtained. Isolation of these mutants or variants and preliminary identification of their anthracycline products are described.

Anthracyclines↗