著者

HISAO EKIMOTO HIROSHI KURAMOCHI KATSUTOSHI TAKAHASHI AKIRA MATSUDA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.33, no.4, pp.426-434, 1980 (Released:2006-04-12)

参考文献数

18

被引用文献数

21 22

---

The kinetics of the reaction of BLM-Fe(II)-O2 with DNA in the absence or presence of 2-mercaptoethanol (2-ME) were studied. The total number of bases released by BLM-Fe(II)-O2 in the presence of 2-ME increased about 6.5 times more than that in the absence of 2-ME in the reaction of 6 hours at 37°C. The molar ratios of the released bases ware little affected by the reaction time, temperature or 2-ME. Among the four bases, thymine was preferentially released. On the basis of a reaction scheme of BLM-Fe(II)-O2 with DNA, the equations were derived by the steady-state method. In the absence of 2-ME, the release of bases from DNA was dependent on the concentration of BLM-Fe(II)-O2, but independent of the concentration of DNA. In the presence of 2-ME, a biphasic reaction was observed; the first one is due to BLM-Fe (II) which originally existed and the second one is due to BLM-Fe(II) produced by the reduction of BLM-Fe(III) with 2-ME. In the second reaction, the rate of the release of bases from DNA was proportional to the concentration of BLM-Fe(II) and 2-ME, but inversely proportional to the concentration of DNA. The rate-determining step in the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was found to be the reduction of BLM-Fe(III) to BLM-Fe(II). By these kinetic studies, the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was elucidated to proceed in a catalytic fashion. Furthermore, the maximum number of bases released by BLM from DNA was one base per twelve to thirteen bases.

著者

HISAO EKIMOTO KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.8, pp.1077-1082, 1985 (Released:2006-04-19)

参考文献数

12

被引用文献数

25 34

---

Lipid peroxidation catalyzed by bleomycin (BLM)-metal complexes was studied in vitro using arachidonic acid as the substrate. Iron complexes of BLM caused extensive lipid peroxidation, but other metal complexes did not. The lipid peroxidation caused by the iron complexes was inhibited by antioxidants such as dl-α-tocopherol, ascorbic acid etc., but not by other scavengers of hydroxyl and superoxide radicals, and of singlet oxygen. Cyanide ion suppressed the lipid peroxidation caused by BLM-Fe(II), but did not suppress the peroxidation activity of BLM-Fe(III). The peroxidation activity of BLM-Fe(II) was lost instantly by pre-incubation of the complex at 37°C before mixing with arachidonic acid, but that of BLM-Fe(III) was not. These results indicate that the active form for the lipid peroxidation derived from BLM-Fe(II) differs from that of BLM-Fe(III).

著者

HISAO EKIMOTO MINAKO AIKAWA TAKAO OHNUKI KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.1, pp.94-98, 1985 (Released:2006-04-19)

参考文献数

16

被引用文献数

5 6

---

Pulmonary fibrosis in mice induced by peplomycin (PEP) was suppressed by administration of anti-inflammatory agents such as prednisolone and D-penicillamine during or after the administration of PEP. Pulmonary fibrosis was also suppressed by administration of cyclophosphamide, an immunosuppressive antitumor agent before, during or after the administration of PEP. The pulmonary fibrosis in athymic nude mice induced by PEP was less than that in normal mice. The low response in the nude mice was enhanced by transfer of thymocytes to the same level as that in the normal mice. This suggests that the immune system, especially thymus-dependent immunity, is involved in the pulmonary fibrosis induced by PEP.

著者

HISAO EKIMOTO KINIIHIKO TAKADA KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.37, no.6, pp.659-663, 1984 (Released:2006-04-19)

参考文献数

30

被引用文献数

7 5

---

The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16μg of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2 similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2 the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2 the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.

著者

ISAMI TAKAHASHI KEI-ICHI TAKAHASHI MICHIO ICHIMURA MAKOTO MORIMOTO Kozo ASANO ISAO KAWAMOTO FUSAO TOMITA HIROFUMI NAKANO

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.41, no.12, pp.1915-1917, 1988-12-25 (Released:2006-04-19)

参考文献数

6

被引用文献数

103 159

著者

J. PATRICK MCGOVREN GEORGE L. CLARKE EVELYN A. PRATT THOMAS F. DEKONING

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.37, no.1, pp.63-70, 1984 (Released:2006-04-19)

参考文献数

14

被引用文献数

78 115

---

It was previously shown that the potent new DNA-binding antibiotic, CC-1065, prolonged life span, but was not curative, when administered to mice bearing a variety of transplantable tumors. In this paper we show results of preliminary studies indicating that CC-1065 caused lethal delayed hepatotoxicity at therapeutic antineoplastic doses. In non-tumor-bearing mice toxic deaths were delayed ca 50 days after a single iv dose of 12.5μg/kg and as much as 70 days after 10μg/kg was given ip. Intravenous mouse LD50's were 9μg/kg, single dose, and 0.3μg/kg/day, five daily doses. Intraperitoneal LD50's were 0.53-6.90μg/kg, single dose, and 0.14μg/kg/day, five daily doses. Mice treated with high doses iv died within 12 days with frank hepatic necrosis, whereas delayed deaths at lower doses were associated with changes in hepatic mitochondrial morphology. This suggested that separate mechanisms of hepatotoxicity were operative at high and low dose ranges. Attempts to prevent the delayed toxicity of CC-1065 in the mouse by treatment with WR-2721, N-acetylcysteine, phenobarbital, Aroclor 1254, and 3-methylcholanthrene were unsuccessful; no effect on the LD50 or the times of death was observed. Lethal doses in the rabbit were similar on a body surface area basis to those in the mouse; evidence of hepatotoxicity was also observed in the rabbit.

著者

HYUN-JIN LEE IN-KOO RHEE KYUNG-BOK LEE ICK-DONG YOO KYUNG-SIK SONG

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.53, no.7, pp.714-719, 2000-07-25 (Released:2008-09-19)

参考文献数

28

被引用文献数

24 36

著者

JI-SOOK HWANG KYUNG-SIK SONG WON-OON KIM TAE-HO LEE HIROYUKI KOSHINO ICK-DONG YOO

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.50, no.9, pp.773-777, 1997-09-25 (Released:2006-11-25)

参考文献数

22

被引用文献数

21 35

著者

鎌田 英男 若木 重敏 工藤 士郎 熊部 潔 香川 恒雄

出版者

Japan Antibiotics Research Association

雑誌

The Journal of Antibiotics, Series B (ISSN:04478991)

巻号頁・発行日

vol.11, no.1, pp.1-15, 1958

---

Carzinophilinは, 秦等によつて, 土壌放線菌の吉田肉腫に対する抗腫瘍性を検索中発見された抗腫瘍性物質である。本物質を産生する放線菌は<I>Streptomyces sahachiroi</I>と名付けられ, 培養条件の検討およびCarzinophilinの抽出に関する報告は既に秦等1) によつて発表されている。更に本物質の結晶化に関する研究は, 鎌田等2) によつて完成され, 島田3) 等を中心とした130余例に上る臨床実験を経て, 有効な抗腫瘍剤として使用されているものである。<BR>Carzinophilinの性質の概略を述べると,<I>St. sahachiroi</I>の培養液から醋酸ブチルに転溶し, メタノール添加によつて白色針状結晶として得られる。水に難溶であるが, pH9.0附近の重曹水には少しとける。水溶液中の紫外部吸収は, 218および250mμ附近に極大値を示す。臨床的には腫瘍の軟化縮小, 腫瘍細胞の崩壊が起り, 症状の緩解, 生存日数の延長がみられる。腫瘍別にみると, 肉腫, 白血病 皮膚癌, 胃癌, その他に効いている。実際, 腫瘍患者の治療にも多く使われているが, 薬理作用の一端を検討したので, ここに報告する。<BR>先ず<I>in vitro</I>において, 薬剤と腫瘍細胞と接触させ, 薬剤が細胞の原形質膜を破つて侵入し4), 代謝機構のどこかに阻害を示し, やがて細胞の変性崩壊または分裂等の作用として現われる過程を逐次追及した。次いで,<I>in vivo</I>において, その作用がどこまで再現されるか, 更に担癌動物にCarzinophilinを投与し腫瘍の増殖経過ならびに担癌動物に与える影響を毒性および正常機能の回復という面から検討した。特に腫瘍の悪性度や, 進行度と密接に関連していると考えられている肝カタラーゼ活性に着目し, Carzinophilin処理後の肝カタラーゼ活性から全身状態の緩解を推定した5), 6)。以下, 8章にわけ逐次報告する。

著者

S. N. SEHGAL H. BAKER Claude VÉZINA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.28, no.10, pp.727-732, 1975 (Released:2006-04-12)

参考文献数

7

被引用文献数

42 720

---

Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus NRRL 5491. It was isolated from the mycelium by solvent extraction, purified by silica gel column chromatography and crystallized as a colorless solid which melts at 183-185°C and has the empirical formula C56H89NO14. From its characteristic ultraviolet absorption spectrum rapamycin can be classified as a triene. It is highly active against various Candida species, especially Candida albicans. Its activity is compared with that of amphotericin B, candicidin and nystatin.

著者

KAYOKO SUZUKAKE-TSUCHIYA MAKOTO HORI NOBUYOSHI SHIMADA MASA HAMADA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.41, no.5, pp.675-683, 1988-05-25 (Released:2006-04-19)

参考文献数

6

被引用文献数

3 5

---

Deoxypheganomycin D, a specific inhibitor of mycobacteria, inhibits the growth in vitro of Mycobacterium smegmatis ATCC 607 (M. 607) bacteriostatically at concentrations as high as 7×10-5M. It shows no cross-resistance to paromomycin, capreomycin, viomycin, streptothricin, kanamycin and streptomycin. Deoxypheganomycin D at 2.8×10-7M where the cell growth of M. 607 is only partially inhibited does not significantly inhibit DNA, RNA or protein synthesis but leads to marked decrease (13 % of control) in [14C]glycerol-derived radioactivity in cell-walls. In the presence of 7×10-6M deoxypheganomycin D, the influx of leucine but not thymidine is affected while the reverse is true with efflux. The data suggest that the effect of deoxypheganomycin D on M. 607 may be related to both the cell membrane and specific mycobacterial lipid like components of the cell-wall.

著者

KIYOSHI TSUJI JOHN F. GOETZ

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.31, no.4, pp.302-308, 1978 (Released:2006-04-12)

参考文献数

16

被引用文献数

27 36

---

Reverse phase high performance liquid chromatography (HPLC) was used as a rapid means of monitoring the erythromycin and the tetracycline fermentation processes. The sample preparation process for tetracycline in the fermentation broth includes simple dilution and filtration through a Millipore filter prior to injection into the HPLC column. Fermentation broth samples showed no interference, and excellent separation for selective determination of tetracycline, 4-epitetracycline, anhydrotetracycline, chlortetracycline, and 4-epianhydrotetracycline was obtained. The relative standard deviation for the HPLC analysis for tetracycline is about one percent and the correlation coefficient between the HPLC and the spectrophotometric assay methods is better than 0.994.The sample preparation procedure for erythromycin determination in fermentation broth requires solvent cleanup and extraction processes. The chromatographic analysis takes approximately 25 minutes, and the HPLC method is capable of separating and quantifying erythromycins A, B, C, and various epimers and degradation compounds. The correlation coefficient between the HPLC and the microbiological assay method is 0.970.

著者

MIKIO SAWADA TOMOYOSHI HOSOKAWA TSUNEO OKUTOMI KUNIO ANDO

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.26, no.11, pp.681-686, 1973-11-25 (Released:2006-04-12)

参考文献数

15

被引用文献数

24 28

---

Ascofuranone significantly reduced serum lipid levels of rats fed with normal diet 6 hours after a single oral administration of 108 mg/kg. When the antibiotic was orally given for consecutive 10 days to normolipidemic rats, the treatment resulted in marked reduction of serum cholesterol, triglycerides, phospholipids and free fatty acids without affecting organ weight gain, serum total protein, albumin/globulin ratio and serum transaminases. Reduction was also noted with cardiac cholesterol content but liver total sterol and fecal sterol excretion were unchanged. Acute toxicity of ascofuranone is weak to mice and rats and the antibiotic did not induce hepatomegaly which is the main side effect of a positive control agent, ethyl-p-chlorophenoxyisobutyrate.

著者

JUNJI MAGAE JUNICHI HAYASAKI YUKO MATSUDA MITSUYUKI HOTTA TOMOYOSHI HOSOKAWA SEIKICHI SUZUKI KAZUO NAGAI KUNIO ANDO GAKUZO TAMURA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.41, no.7, pp.959-965, 1988-07-25 (Released:2006-04-19)

参考文献数

20

被引用文献数

34 41

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Ascofuranone demonstrated antitumor activity against FM3A murine mammary carcinoma, implanted in the peritoneal cavity of syngeneic mice, C3H/He. It was more effective by treatment prior to implantation than by that after implantation. Treatment with ascofuranone also increased splenic cytotoxicity and phagocytic activity of host animal cells. Moreover, ascofuranone induced inflammatory cells in the peritoneal cavity which are mainly composed of polymorpho-nuclear leukocytes and macrophages. These cells are more potent in cytotoxicity against FM3A cells than with resident peritoneal cells. The antitumor activity of ascofuranone was suppressed by ip administration of silica, just prior to tumor implantation. These results suggest that the prophylactic antitumor activity of ascofuranone is expressed through the activation of phagocytes. Ascofuranone also suppressed pulmonary metastasis of B16 melanoma and Lewis lung carcinoma. Treatment after tumor implantaion failed to suppress the metastasis. Single treatment of ascofuranone 4 days prior to implantation decreased the metastasis of Lewis lung carcinoma but not that of B16, whereas single treatment of ascofuranone 24 hours prior to the tumor implantation decreased the metastasis of B16 but not that of Lewis lung carcinoma.

著者

HIROSHI SASAKI TOMOYOSHI HOSOKAWA MIKIO SAWADA KUNIO ANDO

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.26, no.11, pp.676-680, 1973-11-25 (Released:2006-04-12)

参考文献数

15

被引用文献数

43 68

---

A new antibiotic with hypolipidemic activity, ascofuranone, C23H29C1O5, and related substance, ascofuranol, C23H31C1O5, were isolated from the filter cake of the fermented broth of Ascochyta viciae LIBERT, an ascochlorin-producing fungus, and their structures were elucidated. They possess 3-substituted-5-chloro-orcylaldehyde moiety with novel sesquiterpenyl side chains.

著者

JEAN-JACQUES SANGLIER VALERIE QUESNIAUX THEODOR FEHR HANS HOFMANN MARION MAHNKE KLAUS MEMMERT WALTER SCHULER GERHARD ZENKE LILIANE GSCHWIND CLAUDINE MAURER WOLFGANG SCHILLING

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.52, no.5, pp.466-473, 1999-05-25 (Released:2008-09-19)

参考文献数

20

被引用文献数

52 112 105

---

A novel class of macrolides for which the name sanglifehrins is proposed, has been discovered from actinomycete strains based on their high affinity binding for cyclophilin A (CypA), an immunophilin originally identified as a cytosolic protein binding cyclosporin A (CsA). The sanglifehrins were produced by Streptomyces sp. A92-308110. They were isolated and purified by extraction and several chromatographic, activity-guided steps. Sanglifehrins A and B exhibit a 10-20 fold higher affinity for CypA than CsA, whereas the affinity of sanglifehrins C and D for CypA is comparable to that of CsA. Sanglifehrins exhibit a lower immunosuppressive activity than CsA when tested in the mixed lymphocyte reaction. Their in vitro activity indicates that they belong to a novel class of immunosuppressants.

著者

AKIRA TSUJI HIDEKI HIROOKA IKUMI TAMAI TETSUYA TERASAKI

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.39, no.11, pp.1592-1597, 1986 (Released:2006-04-19)

参考文献数

18

被引用文献数

12 16

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Transport of a new cephalosporin developed for oral use, FK089, has been studied with the rat everted small intestine in vitro. Uptake was found to be pH-dependent with the maximum rate at an acidic pH below 5 and with a 5-fold lower rate at pH 7.0. The shape of the pH-rate profile was very similar to that of cefixime and different from that of pH-lipophilicity profile of FK089. The saturation kinetics of the uptake of FK089 were demonstrated at pH 5.0. By correcting the nonsaturable rate process, the kinetics of the mutual inhibition of FK089 uptake by cefixime and cefixime uptake by FK089 were all consistent with competitive type inhibition. The results indicate that carrier-mediated transport is responsible for transport of cephem antibiotics without an α-amino group in the side chain at the 7-position of the cephem nucleus in the intestinal brush-border membrane.