Aldecalmycin, a new antimicrobial antibiotic from Streptomyces.
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Biomedical subjects
Publications and source records attributed to T Sawa.
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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.
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.
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We examined the effect of various polyether antibiotics on colchicine resistance in multidrug-resistant KB-C4 cells which exhibit about 4,000-fold resistance to colchicine. As a result, 4 out of 14 polyether antibiotics were found to reverse colchicine resistance. Among them, laidlomycin was the most potent. It potentiated colchicine cytotoxicity on KB-C4 cells about 700-fold at 1 microgram/ml. Degree of potentiation was calculated by dividing of the IC50 value of colchicine in the absence of a polyether antibiotic by the IC50 value of colchicine in the presence of the polyether antibiotic. Monensin, dianemycin, and leuseramycin at 3 micrograms/ml also potentiated the cytotoxicity, about 100-fold. We previously reported that inostamycin is a potent chemosensitizer in KB-C4 cells. Although lysocellin has a structure very similar to that of inostamycin, it didn't reverse colchicine resistance. It slightly increased [3H]vinblastine accumulation in KB-C4 cells and weakly inhibited the [3H]vinblastine binding to KB-C4 plasma membranes.
Sequence-specific recognition of oligodeoxynucleotide isomers (TTTATT and TTATTT) was achieved by using polyacrylamide-poly(9-vinyladenine) conjugated gel filled capillary affinity gel electrophoresis. It was found that the interaction between poly(9-vinyladenine) and the isomers was dependent on the sequential thymidylic acids of them.
Interstitial lactate concentration in rat skeletal muscle was continuously measured using a microdialysis method following an acute hemorrhage. For comparison, similar measurements were also performed for liver. Normal lactate levels of skeletal muscle and liver interstitium were 0.58 +/- 0.10 mM and 1.23 +/- 0.04 mM, respectively. After withdrawal of 30% of the estimated total blood volume within 3 min, a constant high blood lactate level was achieved. The lactate concentrations in muscle and liver interstitium also increased to 270 and 210% of the basal levels, respectively, but they did not exceed the blood level. These findings led us to hypothesize that skeletal muscle as well as liver functions as a lactate consumer rather than a producer after acute hemorrhage.
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New anthracycline antibiotics, identified as epsilon-rhodomycinone glycosides, were isolated from the culture broth of a blocked mutant of beta-rhodomycin-producing Streptomyces violaceus A262. They were designated as epelmycins A, B, C, D and E, and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with known anthracycline antibiotics.
New anthracycline antibiotics, designated as obelmycins A, D, E, F and G, were isolated from the culture broth of a variant strain of beta-rhodomycin-producing Streptomyces violaceus A262, identified as beta-isorhodomycinone glycosides and gamma-isorhodomycinone glycosides and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with some known anthracyclines.
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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.
The accuracy of measurements on a sample obtained via either T-connecter or three-way stopcock connected directly with an indwelling catheter was comparatively evaluated. The sample was obtained through them after drawing glucose standard fluid (100 mg.dl-1) into a catheter which was primed with saline. The influence of sample volume and discarded volume on the glucose concentration in the sample was investigated, respectively. The results showed that both sample volume and discarded volume required smaller amount with a T-connecter than with a three-way stopcock to obtain more accurate measurements. The results also suggested that remaining discard aliquot in the connecting port of the three-way stopcock might influence the accuracy of the obtained sample when the sample volume was small.
Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.
Thermochemotherapy was performed on gastric cancer cases of hepato-metastasis. The subjects were 12 gastric cancer cases having hepato-metastatic lesions (10 synchronous, 2 heterochronous). Using 8 or 13.58 MHz-dielectric heating apparatus, thermotherapy was carried out for 40-60 min (twice a week, 5-35 times, averaging 12.8 per case) at an intra-tumoral temperature greater than 42 degrees C. Chemotherapy consisted of hepato-arterial infusion of MMC 10 mg/BW, CDDP 75 mg/m2 once per 3-4 weeks and consecutive daily administration p.o. of UFT 800 mg/BW. Effect greater than PR was noted in 75% (9/12) on the whole and in 100% (5/5) and 57% (4/7) for H1-2 and H3, respectively. Mean and 50% survival periods were 9.3 and 7.2 months, respectively, with a one-year survival rate of 38%. Chemotherapy-induced side effects were nausea and vomiting in 83% and leukopenia and thrombopenia in 67%, while the only thermotherapy-induced side effect was subcutaneous fatty tissue necrosis in 3 cases. The above results suggested the effectiveness of the present thermochemotherapy in the treatment of hepato-metastasis of gastric cancer.
We report a case of pulmonary parenchymal leiomyoma. The patient was a 35- year-old female with a tumor in anterobasal segment of the left lung. Enucleation was performed. The tumor was ball type and 2 cm in diameter, showing smooth and reddish brown cut surface. Microscopic and electron microscopic histology proved it to be leiomyoma.