著者
KIMBERLY D. MCBRIEN RONALD L. BERRY SUSAN E. LOWE KIM M. NEDDERMANN ISIA BURSUKER STELLA HUANG STEVEN E. KLOHR JOHN E. LEET
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.48, no.12, pp.1446-1452, 1995-12-25 (Released:2006-04-19)
参考文献数
6
被引用文献数
22 28

The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2, 4-dienoic acid, 3-hydroxy-2, 4, 16-trimethylheptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the Ml09 cell line.
著者
TORU KINO HIROSHI HATANAKA SUSUMU MIYATA NORIAKI INAMURA MICHIHISA NISHIYAMA TOSHIMI YAJIMA TOSHIO GOTO MASAKUNI OKUHARA MASANOBU KOHSAKA HATSUO AOKI TAKENORI OCHIAI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.40, no.9, pp.1256-1265, 1987-09-25 (Released:2006-04-19)
参考文献数
16
被引用文献数
241 574

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1nM and 10nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
著者
中井 悠斎 朝田 康夫 祖父江 昌彦 塩崎 華子
出版者
Japan Antibiotics Research Association
雑誌
The Journal of Antibiotics, Series B (ISSN:04478991)
巻号頁・発行日
vol.20, no.3, pp.191-193, 1967

過去においては, 外科的手術創や熱傷等の2次感染の起炎菌はブドウ球菌がその主役を演じていた。しかし, 近年のすさまじい抗生物質の開発普及によつて, ブドウ球菌感染症は著るしく減少し, これに代つてグラム陰性桿菌の2次感染が注目されるにいたつた。緑膿菌をはじめとするこれらグラム陰性桿菌感染症の増加については, 広域抗生物質の長期投与によるこれら自然耐性をもつ菌の菌交代現象, 副腎皮質ホルモン剤の使用等の諸因子が挙げられている。<BR>さて, われわれ皮膚科領域においては, 広汎な熱傷の治療中に緑膿菌の2次感染がしばしば起り, 患者の治療面に, あるいは予後にいくつかのやつかいな問題を提供する。近年, 第3度熱傷に対しては, 従来の軟膏療法に代わつて早期植皮術の施行が治療日数の短縮のほか, のちの肥厚性瘢痕の発生, 瘢痕拘縮等を予防するという面において, 最良の方法であるといわれて来た。しかし, この間, 緑膿菌感染をひき起すと創傷の治癒傾向遅延, 植皮術のさいの皮片の生着不良, あるいは発熱, 等の全身症状から敗血症にまでいたる種々の合併症を併発し, 熱傷の治療に大きな障害となつていることは, 衆知の事実である。しかし, 今日においても, 緑膿菌感染に対しては特効的薬剤に乏しい現状である。今回, 我々は新らしい抗生物質カスガマイシンを緑膿菌の感染をともなう熱傷患者に対して注射あるいは外用として使用する経験を得るので, 報告する。
著者
宮本 泰 佐藤 直行 三浦 馨 柳沢 謙
出版者
Japan Antibiotics Research Association
雑誌
The Journal of Antibiotics, Series B (ISSN:04478991)
巻号頁・発行日
vol.7, no.7, pp.246-250, 1954

先に細谷1) らは, 本邦の土壌から分離した放線菌の1株H-365株が, 抗菌スペクトル並びに動物に対する低い毒性などの点でStreptomycin (SM) に類似の性質を示す新抗生物質を産生することを見出し, この株が<I>Streptomyces reticule</I>に属することから, この物質をReticulinと命名した。後に, BENEDICT2) らはscreeningの途上でやはり日本 (千葉県) において採取された土壌の2っの別々のサンプルから得られた2株が, SM類似の抗生物質を産生することを見出したが, この株は従来SM産生株として知られている<I>S. griseus</I>及び<I>S. bikiniensis</I>とは異なる新種で, 彼らはこれを<I>S. griseocarneus</I>と命名し, その有効産生物質はHydroxystreptomycinであることを指摘した。<BR>細谷3) らはその後, screeningを継続して2,000種以上の分離放線菌の中から, グラム陽性及びグラム陰性菌に有効な抗生物質産生株100株余を分離したが, その中からreticulin産生株として5株を得て, このものの生物学的性状, 有効物質の精製などを研究し, 得られたreticulinを用いてモルモットに於ける実験的結核症に対する治療実験をおこない, 著るしい効果が見られたことを報告4)した。更に, 細谷5) らは, <I>S. reticule</I>とBENEDICTらの得た<I>S. griseocarneus</I>との異同並びにそれらの産生物質であるreticulinとhydroxystreptonlycinとの異同を詳細に研究し, これらの産生株は分類学的に異なるものであること, 並びにreticulinとhydroxystreptomycinとは化学的に同一物質であることを結論するに至つた。<BR>著者らは, 1951年から1952年にかけて, 当時細谷から依頼を受けたreticulinのサンプルを用いて, モルモットの実験的結核症に対して長期の治療実験をおこない, 遠隔治療成績をも含めて, 同時に治療対照として用いたSMと同程度の著るしい成績を認め, 昭和27年6月文部省綜合研究結核研究委員会化学療法研究科会に報告した。その時の実験では, 当時までに発見された主な抗結核剤, 即ちPAS及びTB1をも同時に最終的に比較をおこなう目的の下に, 遠隔成績の観察をも兼ねて多数の動物群を編成したが, 不運にも溶血連鎖球菌による肺炎の流行に遭遇し, 実験動物の多数が罹患, 或いは斃死するに至り, 殊に治療中止後の遠隔成績を見るための残存動物群における混合感染が甚だしく, 実験成績の正確な批判に少なからず支障を来たした。以上の事実並びに膨大な成績表のために適当な誌上発表の機会を失したが, 今回, reticulin治療群とSM治療群の部分だけを他から切りはなして, 対照群との比較成績を, ここに報告する次第である。幸い, この両治療群のみは治療中の実験群のうちでも溶血連鎖球菌の汚染をうけた個体が少なかつた。治療中止後の観察群は大部分が混合感染をうけた。混合感染の有無は剖検表の備考欄に記載してあるから成績の判読に際して参照されたい。治療実験に入るに先立ち, reticulinの結核菌に対する発育抑制効果をSMのそれと比較した成績を示した。
著者
CLAUDE VÉZINA ALICIA KUDELSKI S. N. SEHGAL
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.721-726, 1975 (Released:2006-04-12)
参考文献数
6
被引用文献数
244 647

A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibioticproducing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 μg/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.
著者
IWAO YAMAZAKI YOSHIHIRO SHIRAKAWA TAKESHI FUGONO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.34, no.11, pp.1476-1485, 1981 (Released:2006-04-12)
参考文献数
18
被引用文献数
2

The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-aminohippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with the highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanism of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.
著者
TREW SALLY J. WRIGLEY STEPHEN K. PAIRET LYDIE SOHAL JESS SHANU-WILSON PATRICK HAYES MARTIN A. MARTIN STEVEN M. MANOHAR RAVI N. CHICARELLI-ROBINSON M. INÊS KAU DAVID A. BYRNE COLIN V WELLINGTON ELIZABETH M. H. MOLONEY JANET M. HOWARD JUDITH HUPE DONALD OLSON ERIC R.
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.53, no.1, pp.1-11, 2000
被引用文献数
25

A series of halogenated pyrrolo [2, 1-b] [1, 3] benzoxazines (<b>1</b>-<b>9</b>) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIMB40808), identified as <i>Streptomyces rimosus</i>, during a microbial extract screening programme to identify inhibitors of bacterial histidine kinase. The structures of these compounds were elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The structure of <b>1</b> was confirmed by X-ray crystallographic studies. Compounds <b>5</b> and <b>6</b> were produced in fermentations in the presence of NaBr and Nal respectively. The most abundant member of the series, streptopyrrole, <b>1</b>, inhibited the nitrogen regulator II (NRII) histidine kinase from <i>Escherichia coli</i> with an IC<sub>50</sub> of 20μM and exhibited antimicrobial activity against a range of bacteria and fungi.
著者
MASARU YOSHIDA MASAMI EZAKI MICHIZANE HASHIMOTO MICHIO YAMASHITA NOBUHARU SHIGEMATSU MASAKUNI OKUHARA MASANOBU KOHSAKA KOKI HORIKOSHI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.43, no.7, pp.748-754, 1990-07-25 (Released:2006-04-19)
参考文献数
12
被引用文献数
46

Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5, 6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.
著者
YASUHIRO IGARASHI KATSUYUKI FUTAMATA TSUYOSHI FUJITA AKIRA SEKINE HISATO SENDA HIDEO NAOKI TAMOTSU FURUMAI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.56, no.2, pp.107-113, 2003-02-25 (Released:2009-01-27)
参考文献数
9
被引用文献数
38 51

In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03μg/ml, more potent than amphotericin B (MIC: 0.1-0.5μg/ml) or itraconazole (MIC: 0.03-0.2μg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3μg/ml.
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
42 435

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 2

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 29

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 17

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 36

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.