13 results on '"Ikuya Yano"'
Search Results
2. Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model.
- Author
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Takayuki Yoshino, Jun Miyazaki, Takahiro Kojima, Shuya Kandori, Masanobu Shiga, Takashi Kawahara, Tomokazu Kimura, Takashi Naka, Hideyasu Kiyohara, Miyuki Watanabe, Sho Yamasaki, Hideyuki Akaza, Ikuya Yano, and Hiroyuki Nishiyama
- Subjects
Medicine ,Science - Abstract
Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy.
- Published
- 2019
- Full Text
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3. Lipids and Fatty Acids of Antarctic Giant Fish
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Yoshimi OHNO, Ikuya YANO, and Osamu WAGURI
- Subjects
Geography (General) ,G1-922 - Abstract
Lipid and fatty acid composition of skeletal muscle of antarctic giant fish (Dissostichus mawsoni NORMAN) were examined. Thin-layer and column chromatography showed that the neutral lipids made up 98% of the total lipids, while phospholipids only 2% or less. The direct gas chromatographic analysis of triglycerides revealed that the major molecular species were C_, C_, C_, C_, C_ and C_, that their fatty acid composition resembled the other edible oil of marine fishes, and that the major components were C_, C_, C_, C_, C_, C_ and C_ with smaller amounts of C_, C_ and C_. The positional distributions of fatty acid on glycerides was also determined by lipase and phospholipase A_2 treatment and it showed that saturated and monoenoic fatty acids occurred in 1 position, while polyunsaturated fatty acids in 2 position, exclusively.
- Published
- 1976
- Full Text
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4. Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model
- Author
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Takahiro Kojima, Ikuya Yano, Miyuki Watanabe, Jun Miyazaki, Takayuki Yoshino, Masanobu Shiga, Hideyasu Kiyohara, Tomokazu Kimura, Shuya Kandori, Hideyuki Akaza, Takashi Kawahara, Takashi Naka, Sho Yamasaki, and Hiroyuki Nishiyama
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,medicine.medical_treatment ,Cancer Treatment ,CD8-Positive T-Lymphocytes ,Biochemistry ,Mice ,White Blood Cells ,0302 clinical medicine ,Cancer immunotherapy ,Animal Cells ,Medicine and Health Sciences ,Cationic liposome ,Mice, Inbred C3H ,Liposome ,Multidisciplinary ,Molecular Structure ,T Cells ,Chemistry ,Immunogenicity ,Animal Models ,Keto Acids ,Bladder Cancer ,Lipids ,Mycolic Acids ,Oncology ,Experimental Organism Systems ,Syngeneic Graft ,030220 oncology & carcinogenesis ,BCG Vaccine ,Medicine ,Female ,Immunotherapy ,Cellular Structures and Organelles ,Cellular Types ,Research Article ,Urology ,Immune Cells ,Science ,Immunology ,Mice, Nude ,Mouse Models ,Cytotoxic T cells ,Research and Analysis Methods ,Cancer Vaccines ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,Model Organisms ,Cell Walls ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Vesicles ,Particle Size ,Blood Cells ,Bladder cancer ,Biology and Life Sciences ,Cancers and Neoplasms ,Cell Biology ,medicine.disease ,Mice, Inbred C57BL ,Genitourinary Tract Tumors ,030104 developmental biology ,Urinary Bladder Neoplasms ,Liposomes ,Animal Studies ,Cancer research - Abstract
Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy.
- Published
- 2019
5. Lipid Phenotype of Two Distinct Subpopulations of Mycobacterium bovis Bacillus Calmette-Guérin Tokyo 172 Substrain*
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Saburo Yamamoto, Nagatoshi Fujiwara, Hisashi Ogura, Jun ichi Maeyama, Naoya Ohara, Mamiko Niki, Kazuo Kobayashi, Shinji Maeda, Takashi Naka, and Ikuya Yano
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Antigenicity ,Genotype ,Pyruvate Synthase ,Molecular Sequence Data ,Carbohydrates ,Gene mutation ,Biochemistry ,complex mixtures ,Microbiology ,Mycobacterium tuberculosis ,Mice ,Glycolipid ,Antigen ,Escherichia coli ,Animals ,Molecular Biology ,Mice, Knockout ,Mycobacterium bovis ,biology ,Models, Genetic ,Escherichia coli Proteins ,fungi ,Fatty Acids ,Cell Biology ,biology.organism_classification ,Mice, Inbred C57BL ,Phenotype ,Mycolic Acids ,Mutation ,BCG Vaccine ,bacteria ,Chromatography, Thin Layer ,Glycolipids ,Tuberculosis vaccines ,BCG vaccine - Abstract
Bacillus Calmette-Guerin (BCG) Tokyo 172 is a predominant World Health Organization Reference Reagent for the BCG vaccine. Recently, the BCG Tokyo 172 substrain was reported to consist of two subpopulations with different colony morphologies, smooth and rough. Smooth colonies had a characteristic 22-bp deletion in Rv3405c of the region of difference (RD) 16 (type I), and rough colonies were complete in this region (type II). We hypothesized that the morphological difference is related to lipid phenotype and affects their antigenicity. We determined the lipid compositions and biosynthesis of types I and II. Scanning electron microscopy showed that type I was 1.5 times longer than type II. Phenolic glycolipid (PGL) and phthiocerol dimycocerosate (PDIM) were found only in type I. Although it has been reported that the RD16 is involved in the expression of PGL, type II did not possess PGL/PDIM. We examined the ppsA-E gene responsible for PGL/PDIM biosynthesis and found that the existence of PGL/PDIM in types I and II is caused by a ppsA gene mutation not regulated by the RD16. PGL suppressed the host recognition of total lipids via Toll-like receptor 2, and this suggests that PGL is antigenic and involved in host responses, acting as a cell wall component. This is the first report to show the difference between lipid phenotypes of types I and II. It is important to clarify the heterogeneity of BCG vaccine substrains to discuss and evaluate the quality, safety, and efficacy of the BCG vaccine.
- Published
- 2011
6. Characterization of the Fucosylation Pathway in the Biosynthesis of Glycopeptidolipids from Mycobacterium avium Complex▿
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Yuji Miyamoto, Noboru Nakata, Takashi Naka, Masahiko Makino, Ikuya Yano, Yumi Maeda, Masanori Kai, and Tetsu Mukai
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Glycosylation ,Rhamnose ,Mycobacterium smegmatis ,Mannose ,Microbiology ,Fucose ,Gas Chromatography-Mass Spectrometry ,Microbial Cell Biology ,chemistry.chemical_compound ,Bacterial Proteins ,Glycosyltransferase ,Molecular Biology ,Fucosylation ,biology ,Molecular Structure ,Cell Membrane ,biology.organism_classification ,Mycobacterium avium Complex ,Biosynthetic Pathways ,chemistry ,Biochemistry ,Genes, Bacterial ,Glucosyltransferases ,Chromosomal region ,biology.protein ,Glycolipids ,Oxidoreductases ,Gene Deletion - Abstract
The cell envelopes of several species of nontuberculous mycobacteria, including the Mycobacterium avium complex, contain glycopeptidolipids (GPLs) as major glycolipid components. GPLs are highly antigenic surface molecules, and their variant oligosaccharides define each serotype of the M. avium complex. In the oligosaccharide portion of GPLs, the fucose residue is one of the major sugar moieties, but its biosynthesis remains unclear. To elucidate it, we focused on the 5.0-kb chromosomal region of the M. avium complex that includes five genes, two of which showed high levels of similarity to the genes involved in fucose synthesis. For the characterization of this region by deletion and expression analyses, we constructed a recombinant Mycobacterium smegmatis strain that possesses the rtfA gene of the M. avium complex to produce serovar 1 GPL. The results revealed that the 5.0-kb chromosomal region is responsible for the addition of the fucose residue to serovar 1 GPL and that the three genes mdhtA , merA , and gtfD are indispensable for the fucosylation. Functional characterization revealed that the gtfD gene encodes a glycosyltransferase that transfers a fucose residue via 1→3 linkage to a rhamnose residue of serovar 1 GPL. The other two genes, mdhtA and merA , contributed to the formation of the fucose residue and were predicted to encode the enzymes responsible for the synthesis of fucose from mannose based on their deduced amino acid sequences. These results indicate that the fucosylation pathway in GPL biosynthesis is controlled by a combination of the mdhtA , merA , and gtfD genes. Our findings may contribute to the clarification of the complex glycosylation pathways involved in forming the oligosaccharide portion of GPLs from the M. avium complex, which are structurally distinct.
- Published
- 2007
7. Identification and Characterization of the Genes Involved in Glycosylation Pathways of Mycobacterial Glycopeptidolipid Biosynthesis
- Author
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Yuji Miyamoto, Tetsu Mukai, Yumi Maeda, Takashi Naka, Masahiko Makino, Noboru Nakata, Ikuya Yano, and Masanori Kai
- Subjects
Glycosylation ,Mutant ,Mycobacterium smegmatis ,Microbiology ,Rhamnose ,Gas Chromatography-Mass Spectrometry ,Microbial Cell Biology ,chemistry.chemical_compound ,Bacterial Proteins ,Molecular Biology ,Gene ,Recombination, Genetic ,biology ,Glycosyltransferase Gene ,Wild type ,Glycopeptides ,biology.organism_classification ,Mycobacterium avium Complex ,Complementation ,chemistry ,Biochemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mutation ,Glycolipids ,Mycobacterium - Abstract
Glycopeptidolipids (GPLs) are major components present on the outer layers of the cell walls of several nontuberculous mycobacteria. GPLs are antigenic molecules and have variant oligosaccharides in mycobacteria such as Mycobacterium avium . In this study, we identified four genes ( gtf1 , gtf2 , gtf3 , and gtf4 ) in the genome of Mycobacterium smegmatis . These genes were independently inactivated by homologous recombination in M. smegmatis , and the structures of GPLs from each gene disruptant were analyzed. Thin-layer chromatography, gas chromatography-mass spectrometry, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analyses revealed that the mutants Δgtf1 and Δgtf2 accumulated the fatty acyl-tetrapeptide core having O -methyl-rhamnose and 6-deoxy-talose as sugar residues, respectively. The mutant Δgtf4 possessed the same GPLs as the wild type, whereas the mutant Δgtf3 lacked two minor GPLs, consisting of 3- O -methyl-rhamnose attached to O -methyl-rhamnose of the fatty acyl-tetrapeptide core. These results indicate that the gtf1 and gtf2 genes are responsible for the early glycosylation steps of GPL biosynthesis and the gtf3 gene is involved in transferring a rhamnose residue not to 6-deoxy-talose but to an O -methyl-rhamnose residue. Moreover, a complementation experiment showed that M. avium gtfA and gtfB , which are deduced glycosyltransferase genes of GPL biosynthesis, restore complete GPL production in the mutants Δgtf1 and Δgtf2, respectively. Our findings propose that both M. smegmatis and M. avium have the common glycosylation pathway in the early steps of GPL biosynthesis but differ at the later stages.
- Published
- 2006
8. Anti-tumor immunity via the superoxide-eosinophil axis induced by a lipophilic component of Mycobacterium lipomannan.
- Author
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Toshihiro Ito, Kiyoshi Hirahara, Atsushi Onodera, Ryo Koyama-Nasu, Ikuya Yano, and Toshinori Nakayama
- Subjects
MYCOBACTERIUM bovis ,EOSINOPHILS ,LIPOARABINOMANNANS ,SUPEROXIDES ,CHEMOKINES - Abstract
Mycobacterium bovis Bacille Calmette--Guérin (BCG) has been shown to possess potent anti-tumor activity particularly in various animal models, while the cellular and molecular mechanisms underlying its activity are not well understood. We found that lipomannan (BCG-LM), a lipophilic component of the mycobacterial cell envelope, specifically inhibits tumor growth and induces the infiltration of eosinophils at local tumor invasion sites. In contrast, neither lipoarabinomannan (BCG-LAM) nor the cell wall of Mycobacterium bovis BCG (BCG-CW) exerted anti-tumor immunity. BCG-LM enhances cytotoxic activity of eosinophils via the increased production of superoxide. Global transcriptomic analyses of BCG-LM-pulsed dendritic cells identified C-C motif ligand (CCL) 5 as a crucial chemokine for the anti-tumor immunity induced by BCG-LM, indicating that CCL5 plays an important role for the accumulation of eosinophils in the tumor microenvironment. Furthermore, BCG-LM and memory T
h 2 cells exerted a synergetic effect on tumor progression by cooperatively enhancing the eosinophil function. Thus, this study revealed an un-identified BCG-LM-mediated anti-tumor mechanism via superoxide produced by infiltrated eosinophils in the tumor microenvironment. Since BCG-LM activates this unique pathway, it may have potent therapeutic potential as immune cell therapy for cancer patients. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
9. Lipid profile of Helicobacter spp.: presence of cholesteryl glucoside as a characteristic feature
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Hideyuki Ito, Noriko Mori, Yoshikazu Hirai, Kenji Yokota, Hisako Hotta, Ikuya Yano, Keiji Oguma, Yasuhiro Kanemasa, Mahmudul Haque, and Israt Jahan
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chemistry.chemical_classification ,biology ,Strain (chemistry) ,Cholesterol ,Fatty Acids ,Fatty acid ,Heterologous ,biology.organism_classification ,Microbiology ,Lipids ,chemistry.chemical_compound ,chemistry ,Glucoside ,Species Specificity ,Helicobacter ,Acinonyx ,lipids (amino acids, peptides, and proteins) ,Cyclopropane fatty acid ,Molecular Biology ,Research Article - Abstract
The lipid and fatty acid profiles of eight Helicobacter spp. (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, "H. rappini" [Flexispira rappini], H. pametensis, Helicobacter sp. strain Bird-B, and Helicobacter sp. strain Bird-C) and the fatty acid profiles of five additional species (H. pylori, H. felis, H. muridarum, H. mustelae, and H. fennelliae) were analyzed and compared. A heterologous fatty acid profile was observed among the Helicobacter spp., and on that basis the species could be divided into two groups. Group A had 19-carbon cyclopropane fatty acid (19:0cyc) and tetradecanoic acid (14:0) as the major fatty acids, and group B characteristically lacked the 19:0cyc and had hexadecanoic acid (16:0) and octadecenoic (18:1) acids as the major fatty acids. The species of group A are primarily gastric colonizers, and those of group B are primarily intestinal colonizers. Seven of the eight species studied showed the unusual and characteristic presence of cholesteryl glucosides (CGs), and most of these seven showed a very large amount (9.7 to 27.4% of the weight of total extractable lipid). The types of CGs and their distribution in different species were as follows: cholesteryl-6-O-acyl-alpha-D-glucopyranoside (cholesteryl-6-O-tetradecanoyl-alpha-D-glucopyranoside in H. nemestrinae and mainly cholesteryl-6-O-dodecanoyl-alpha-D-glucopyranoside in "H. rappini"), cholesteryl-alpha-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, Helicobacter sp. strain CLO-3, and "H. rappini"), and cholesteryl-6-O-phosphatidyl-alpha-D-glucopyranoside (H. nemestrinae, H. acinonyx, H. canis, and Helicobacter sp. strain CLO-3). Besides this, we could also detect cholesteryl acyl glucoside in H. acinonyx, cholesteryl glucoside in Helicobacter sp. strains Bird-B and -C, and cholesteryl phosphatidyl glucoside in "H. rappini" and Helicobacter sp. strain Bird-C. A selective accumulation of free cholesterol was observed in the neutral lipid fractions. On the basis of the detection of CGs in 11 of the 13 species studied so far, the presence of CGs appears to be a characteristic feature of the genus Helicobacter. In view of this and also because of a simple and rapid detection method described herein, the CGs can be used as a valuable chemotaxonomic marker.
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- 1996
10. A murine model of granulomatous colitis with mesenteric lymphadenitis induced by mycobacterial cord factor.
- Author
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Mitsue Sogawa, Takayuki Matsumoto, Hirokazu Yamagami, Tamaki Yamada, Yuriko Ozeki, Ikuya Yano, Yuji Nakajima, Tetsuo Arakawa, and Kenji Kaneda
- Subjects
INFLAMMATION ,COLON diseases ,CYTOKINES ,LYMPHOID tissue - Abstract
Abstract. Granulomatous colitis is a major entity of human intestinal diseases. We previously reported that intravenous injection of mycobacterial cord factor (CF), a potent macrophage activator, induced pulmonary granulomas in mice with enhanced production of Th1 cytokines and chemokines. In this study we made a murine model of granulomatous colitis by intramural injection of CF. A single dose of 300 µg CF was injected into the wall of the rat and mouse colon in the form of liposomes. After 1 week granulomas developed at the injection site, extending from the subserosa to the lamina propria, and persisted for longer than 6 weeks. They were composed mainly of ED1-positive macrophages, which often underwent apoptosis, and CD4
+ and CD8+ lymphocytes, which preferentially infiltrated around the macrophage accumulation. Myofibroblast proliferation was not prominent, and no appreciable fibrosis resulted after the decline of granulomas. Although the intestinal epithelium was involved in inflammation, tissue injuries such as mucosal erosion or ulceration were not induced. When granulomas were formed near the Peyer's patches, they invaded deeply into the lymphoid tissue, producing many small islands. The mesenteric lymph nodes also had many granulomatous islands in the cortex and medulla, but the liver and spleen displayed no granulomatous changes, suggesting that liposomal CF spreads via the lymphatic vessels from the injection site. The CF-induced colonic granulomas associated with mesenteric lymphadenitis will be useful for investigating human granulomatous colitis. [ABSTRACT FROM AUTHOR]- Published
- 2003
11. Separation and identification of molecular species of phospholipids from a gram-negative moderately halophilic bacterium
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Masamiki Masui, Yoshimi Ohno, and Ikuya Yano
- Subjects
Chromatography, Gas ,Hot Temperature ,Bacteria ,biology ,Cardiolipins ,Chemistry ,Phosphatidylethanolamines ,Biophysics ,Cell Biology ,biology.organism_classification ,Biochemistry ,Mass Spectrometry ,Halophile ,Microbiology ,Structural Biology ,Genetics ,Chromatography, Thin Layer ,Molecular Biology ,Phospholipids ,Gram - Full Text
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12. Direct Colony Thin-Layer Chromatography and Rapid Characterization of Serratia marcescens Mutants Defective in Production of Wetting Agents
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Tohey Matsuyama, Masakazu Sogawa, and Ikuya Yano
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Chromatography ,Ecology ,biology ,Mutant ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Enterobacteriaceae ,Thin-layer chromatography ,Microbiology ,Ammonia ,chemistry.chemical_compound ,chemistry ,Serratia marcescens ,Methods ,lipids (amino acids, peptides, and proteins) ,Wetting ,Bacteria ,Food Science ,Biotechnology - Abstract
A bacterial mass (ca. 1 mg) was placed directly on a thin-layer chromatography plate and developed shortly in chloroform-methanol (2:1, vol/vol). After being dried, the bacterial mass was developed in chloroform-methanol-5 M ammonia (80:25:4, vol/vol). The obtained chromatogram indicated the characteristic lipid compositions of the bacteria. So, it became possible to examine bacterial colonies at once for the identification of mutants defective in the production of specific lipids.
- Published
- 1987
13. Essential carbohydrate structure of mycoloyl glycolipids to induce granuloma formation and chemotactic factor generation in mice
- Author
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Isamu Matsunaga, Shiro Oka, and Ikuya Yano
- Published
- 1991
- Full Text
- View/download PDF
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