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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42618完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 白果能(Konan Peck) | |
| dc.contributor.author | Yi-Chung Chang | en |
| dc.contributor.author | 張翼中 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:17:52Z | - |
| dc.date.available | 2014-09-15 | |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-07-27 | |
| dc.identifier.citation | 第一部分
1. Lemaitre, B., Nicolas, E., Michaut, L., Reichhart, J. M., Hoffmann, J. A. (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983 2. Nomura, N., Miyajima, N., Sazuka, T., Tanaka, A., Kawarabayasi, Y., Sato, S., Nagase, T., Seki, N., Ishikawa, K., Tabata, S. (1994) Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement). DNA Res. 1, 47-56 3. Chuang, T., Ulevitch, R. J. (2001) Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim.Biophys.Acta 1518, 157-161. 4. Medzhitov, R. (2001) Toll-like receptors and innate immunity. Nat.Rev.Immunol. 1, 135-145 5. Iwasaki, A., Medzhitov, R. (2004) Toll-like receptor control of the adaptive immune responses. Nat.Immunol. 5, 987-995 6. Boone, D. L., Ma, A. (2003) Connecting the dots from Toll-like receptors to innate immune cells and inflammatory bowel disease. J.Clin.Invest 111, 1284-1286. 7. Rifkin, I. R., Leadbetter, E. A., Busconi, L., Viglianti, G., Marshak-Rothstein, A. (2005) Toll-like receptors, endogenous ligands, and systemic autoimmune disease. Immunol.Rev. 204, 27-42 8. Clevers, H. (2004) At the crossroads of inflammation and cancer. Cell 118, 671-674 9. Xu, Y., Tao, X., Shen, B., Horng, T., Medzhitov, R., Manley, J. L., and Tong, L. (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408, 111-115 10. Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., and Aderem, A. (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103 11. Bulut, Y., Faure, E., Thomas, L., Equils, O., and Arditi, M. (2001) Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling. J. Immunol. 167, 987-994 12. Wyllie, D. H., Kiss-Toth, E., Visintin, A., Smith, S. C., Boussouf, S., Segal, D. M., Duff, G. W., and Dower, S. K. (2000) Evidence for an accessory protein function for Toll-like receptor 1 in anti-bacterial responses. J. Immunol. 165, 7125-7132 13. Heil, F., Hemmi, H., Hochrein, H., Ampenberger, F., Kirschning, C., Akira, S., Lipford, G., Wagner, H., and Bauer, S. (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526-1529 14. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., and Akira, S. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 15. Alexopoulou, L., Holt, A. C., Medzhitov, R., and Flavell, R. A. (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732-738 16. Brightbill, H. D., Libraty, D. H., Krutzik, S. R., Yang, R. B., Belisle, J. T., Bleharski, J. R., Maitland, M., Norgard, M. V., Plevy, S. E., Smale, S. T., Brennan, P. J., Bloom, B. R., Godowski, P. J., and Modlin, R. L. (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285, 732-736 17. Medzhitov, R., Preston-Hurlburt, P., and Janeway, C. A., Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397 18. Sanjuan, M. A., Dillon, C. P., Tait, S. W., Moshiach, S., Dorsey, F., Connell, S., Komatsu, M., Tanaka, K., Cleveland, J. L., Withoff, S., and Green, D. R. (2007) Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 450, 1253-1257 19. Blander, J. M., and Medzhitov, R. (2004) Regulation of phagosome maturation by signals from toll-like receptors. Science 304, 1014-1018 20. Sun, J., Walsh, M., Villarino, A. V., Cervi, L., Hunter, C. A., Choi, Y., Pearce, E. J. (2005) TLR ligands can activate dendritic cells to provide a MyD88-dependent negative signal for Th2 cell development. J.Immunol. 174, 742-7515. 21. Hertz, C. J., Kiertscher, S. M., Godowski, P. J., Bouis, D. A., Norgard, M. V., Roth, M. D., and Modlin, R. L. (2001) Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J. Immunol. 166, 2444-2450 22. Hayashi, E. A., Akira, S., and Nobrega, A. (2005) Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2. J. Immunol. 174, 6639-6647 23. Sanjuan, M. A., Dillon, C. P., Tait, S. W., Moshiach, S., Dorsey, F., Connell, S., Komatsu, M., Tanaka, K., Cleveland, J. L., Withoff, S., Green, D. R. (2007) Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis. Nature 450, 1253-1257 1. 24. Heymann, W. R. (2006) Toll-like receptors in acne vulgaris. J.Am.Acad.Dermatol. 55, 691-692 25. Obonyo, M., Sabet, M., Cole, S. P., Ebmeyer, J., Uematsu, S., Akira, S., Guiney, D. G. (2007) Deficiencies of myeloid differentiation factor 88, Toll-like receptor 2 (TLR2), or TLR4 produce specific defects in macrophage cytokine secretion induced by Helicobacter pylori. Infect.Immun. 75, 2408-2414 26. Ramirez Cruz, N. E., Maldonado, B. C., Cuevas Uriostegui, M. L., Castanon, J., Lopez, M. C., Isibasi, A. (2004) Toll-like receptors: dysregulation in vivo in patients with acute respiratory distress syndrome. Rev.Alerg.Mex. 51, 210-217 27. Sarir, H., Henricks, P. A., van Houwelingen, A. H., Nijkamp, F. P., Folkerts, G. (2008) Cells, mediators and Toll-like receptors in COPD. Eur.J.Pharmacol. 585, 346-353 28. Matsuda, N., Hattori, Y. (2006) Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J.Pharmacol.Sci. 101, 189-198 29. Cristofaro, P., Opal, S. M. (2003) The Toll-like receptors and their role in septic shock. Expert.Opin.Ther.Targets. 7, 603-612 30. Nakamura, M., Shimizu, Y., Sato, Y., Miyazaki, Y., Satoh, T., Mizuno, M., Kato, Y., Hosaka, Y., Furusako, S. (2007) Toll-like receptor 4 signal transduction inhibitor, M62812, suppresses endothelial cell and leukocyte activation and prevents lethal septic shock in mice. Eur.J.Pharmacol. 569, 237-243 31. Meng, G., Rutz, M., Schiemann, M., Metzger, J., Grabiec, A., Schwandner, R., Luppa, P. B., Ebel, F., Busch, D. H., Bauer, S., Wagner, H., Kirschning, C. J. (2004) Antagonistic antibody prevents toll-like receptor 2-driven lethal shock-like syndromes. J.Clin.Invest 113, 1473-1481 32. Johnson, G. B., Brunn, G. J., and Platt, J. L. (2003) Activation of mammalian Toll-like receptors by endogenous agonists. Crit. Rev. Immunol. 23, 15-44 33. Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A., Nacken, W., Foell, D., van der, P. T., Sorg, C., and Roth, J. (2007) Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 13, 1042-1049 34. Barrat, F. J., Meeker, T., Gregorio, J., Chan, J. H., Uematsu, S., Akira, S., Chang, B., Duramad, O., and Coffman, R. L. (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 202, 1131-1139 35. Asagiri, M., Hirai, T., Kunigami, T., Kamano, S., Gober, H. J., Okamoto, K., Nishikawa, K., Latz, E., Golenbock, D. T., Aoki, K., Ohya, K., Imai, Y., Morishita, Y., Miyazono, K., Kato, S., Saftig, P., and Takayanagi, H. (2008) Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis. Science 319, 624-627 36. Rodriguez, D., Keller, A. C., Faquim-Mauro, E. L., de Macedo, M. S., Cunha, F. Q., Lefort, J., Vargaftig, B. B., and Russo, M. (2003) Bacterial lipopolysaccharide signaling through Toll-like receptor 4 suppresses asthma-like responses via nitric oxide synthase 2 activity. J. Immunol. 171, 1001-1008 37. Prinz, M., Garbe, F., Schmidt, H., Mildner, A., Gutcher, I., Wolter, K., Piesche, M., Schroers, R., Weiss, E., Kirschning, C. J., Rochford, C. D., Bruck, W., Becher, B. (2006) Innate immunity mediated by TLR9 modulates pathogenicity in an animal model of multiple sclerosis. J.Clin.Invest 116, 456-464 38. Knuefermann, P., Schwederski, M., Velten, M., Krings, P., Ehrentraut, H., Rudiger, M., Boehm, O., Fink, K., Dreiner, U., Grohe, C., Hoeft, A., Baumgarten, G., Koch, A., Zacharowski, K., Meyer, R. (2008) Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9. Cardiovasc.Res. 78, 26-35 39. Kim, H. S., Han, M. S., Chung, K. W., Kim, S., Kim, E., Kim, M. J., Jang, E., Lee, H. A., Youn, J., Akira, S., Lee, M. S. (2007) Toll-like receptor 2 senses beta-cell death and contributes to the initiation of autoimmune diabetes. Immunity. 27, 321-333 40. Liu, X., Ukai, T., Yumoto, H., Davey, M., Goswami, S., Gibson, F. C., III, and Genco, C. A. (2008) Toll-like receptor 2 plays a critical role in the progression of atherosclerosis that is independent of dietary lipids. Atherosclerosis 196, 146-154 41. Basu, S., Pathak, S. K., Chatterjee, G., Pathak, S., Basu, J., Kundu, M. (2008) Helicobacter pylori protein HP0175 transactivates epidermal growth factor receptor through TLR4 in gastric epithelial cells. J.Biol.Chem. 283, 32369-32376 42. Fukata, M., Chen, A., Vamadevan, A. S., Cohen, J., Breglio, K., Krishnareddy, S., Hsu, D., Xu, R., Harpaz, N., Dannenberg, A. J., Subbaramaiah, K., Cooper, H. S., Itzkowitz, S. H., Abreu, M. T. (2007) Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology 133, 1869-1881 43. He, W., Liu, Q., Wang, L., Chen, W., Li, N., Cao, X. (2007) TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol.Immunol. 44, 2850-2859 44. Pei, Z., Lin, D., Song, X., Li, H., Yao, H. (2008) TLR4 signaling promotes the expression of VEGF and TGFbeta1 in human prostate epithelial PC3 cells induced by lipopolysaccharide. Cell Immunol. 254, 20-27 Ref Type: Journal 45. Bourquin, C., Anz, D., Zwiorek, K., Lanz, A. L., Fuchs, S., Weigel, S., Wurzenberger, C., von der, B. P., Golic, M., Moder, S., Winter, G., Coester, C., and Endres, S. (2008) Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity. J. Immunol. 181, 2990-2998 46. Hamdy, S., Molavi, O., Ma, Z., Haddadi, A., Alshamsan, A., Gobti, Z., Elhasi, S., Samuel, J., and Lavasanifar, A. (2008) Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8+ T cell-mediated anti-tumor immunity. Vaccine 26, 5046-5057 47. Seya, T., Akazawa, T., Uehori, J., Matsumoto, M., Azuma, I., Toyoshima, K. (2003) Role of toll-like receptors and their adaptors in adjuvant immunotherapy for cancer. Anticancer Res. 23, 4369-4376 48. Toll-like receptor signaling in anti-cancer immunity. J.Med.Invest 50, 9-24 49. Burdelya, L. G., Krivokrysenko, V. I., Tallant, T. C., Strom, E., Gleiberman, A. S., Gupta, D., Kurnasov, O. V., Fort, F. L., Osterman, A. L., Didonato, J. A., Feinstein, E., and Gudkov, A. V. (2008) An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science 320, 226-230 50. Mi, J., Zhang, X., Rabbani, Z. N., Liu, Y., Su, Z., Vujaskovic, Z., Kontos, C. D., Sullenger, B. A., and Clary, B. M. (2006) H1 RNA polymerase III promoter-driven expression of an RNA aptamer leads to high-level inhibition of intracellular protein activity. Nucleic Acids Res. 34, 3577-3584 51. Nishikawa, F., Kakiuchi, N., Funaji, K., Fukuda, K., Sekiya, S., and Nishikawa, S. (2003) Inhibition of HCV NS3 protease by RNA aptamers in cells. Nucleic Acids Res. 31, 1935-1943 52. Tuerk, C., and Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505-510 53. Ellington, A. D., and Szostak, J. W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818-822 54. Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H., and Toole, J. J. (1992) Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355, 564-566 55. Lee, J. H., Canny, M. D., De, E. A., Krilleke, D., Ng, Y. S., Shima, D. T., Pardi, A., and Jucker, F. (2005) A therapeutic aptamer inhibits angiogenesis by specifically targeting the heparin binding domain of VEGF165. Proc. Natl. Acad. Sci. U.S.A 102, 18902-18907 56. Rusconi, C. P., Roberts, J. D., Pitoc, G. A., Nimjee, S. M., White, R. R., Quick, G., Jr., Scardino, E., Fay, W. P., and Sullenger, B. A. (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat. Biotechnol. 22, 1423-1428 57. Cerchia, L., Duconge, F., Pestourie, C., Boulay, J., Aissouni, Y., Gombert, K., Tavitian, B., de, F., V, and Libri, D. (2005) Neutralizing aptamers from whole-cell SELEX inhibit the RET receptor tyrosine kinase. PLoS Biol. 3, e123 58. McNamara, J. O., Kolonias, D., Pastor, F., Mittler, R. S., Chen, L., Giangrande, P. H., Sullenger, B., and Gilboa, E. (2008) Multivalent 4-1BB binding aptamers costimulate CD8+ T cells and inhibit tumor growth in mice. J. Clin. Invest 118, 376-386 59. Huang, Y. H., Wei, C. C., Su, Y. H., Wu, B. T., Ciou, Y. Y., Tu, C. F., Cooper, T. G., Yeung, C. H., Chu, S. T., Tsai, M. T., and Yang, R. B. (2006) Localization and characterization of an orphan receptor, guanylyl cyclase-G, in mouse testis and sperm. Endocrinology 147, 4792-4800 60. Mathews, D. H., Disney, M. D., Childs, J. L., Schroeder, S. J., Zuker, M., and Turner, D. H. (2004) Incorporating chemical modification constraints into a dynamic programming algorithm for prediction of RNA secondary structure. Proc. Natl. Acad. Sci. U.S.A 101, 7287-7292 61. Aliprantis, A. O., Yang, R. B., Mark, M. R., Suggett, S., Devaux, B., Radolf, J. D., Klimpel, G. R., Godowski, P., and Zychlinsky, A. (1999) Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 285, 736-739 62. Okusawa, T., Fujita, M., Nakamura, J., Into, T., Yasuda, M., Yoshimura, A., Hara, Y., Hasebe, A., Golenbock, D. T., Morita, M., Kuroki, Y., Ogawa, T., and Shibata, K. (2004) Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6. Infect. Immun. 72, 1657-1665 63. Quesniaux, V. J., Nicolle, D. M., Torres, D., Kremer, L., Guerardel, Y., Nigou, J., Puzo, G., Erard, F., and Ryffel, B. (2004) Toll-like receptor 2 (TLR2)-dependent-positive and TLR2-independent-negative regulation of proinflammatory cytokines by mycobacterial lipomannans. J. Immunol. 172, 4425-4434 64. Nemoto, E., Darveau, R. P., Foster, B. L., Nogueira-Filho, G. R., and Somerman, M. J. (2006) Regulation of cementoblast function by P. gingivalis lipopolysaccharide via TLR2. J. Dent. Res. 85, 733-738 65. Diya, Z., Lili, C., Shenglai, L., Zhiyuan, G., and Jie, Y. (2008) Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces IL-1beta, TNF-alpha and IL-6 production by THP-1 cells in a way different from that of Escherichia coli LPS. Innate Immun. 14, 99-107 66. Takeuchi, O., Hoshino, K., and Akira, S. (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J. Immunol. 165, 5392-5396 67. Meng, G., Rutz, M., Schiemann, M., Metzger, J., Grabiec, A., Schwandner, R., Luppa, P. B., Ebel, F., Busch, D. H., Bauer, S., Wagner, H., and Kirschning, C. J. (2004) Antagonistic antibody prevents toll-like receptor 2-driven lethal shock-like syndromes. J. Clin. Invest 113, 1473-1481 68. Shangguan, D., Li, Y., Tang, Z., Cao, Z. C., Chen, H. W., Mallikaratchy, P., Sefah, K., Yang, C. J., and Tan, W. (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc. Natl. Acad. Sci. U.S.A 103, 11838-11843 69. Koch, T. H., Smith, D., Tabacman, E., and Zichi, D. A. (2004) Kinetic analysis of site-specific photoaptamer-protein cross-linking. J. Mol. Biol. 336, 1159-1173 70. Zhou, Q., and Amar, S. (2007) Identification of signaling pathways in macrophage exposed to Porphyromonas gingivalis or to its purified cell wall components. J. Immunol. 179, 7777-7790 71. Kido, J., Kido, R., Suryono, Kataoka, M., Fagerhol, M. K., and Nagata, T. (2003) Calprotectin release from human neutrophils is induced by Porphyromonas gingivalis lipopolysaccharide via the CD-14-Toll-like receptor-nuclear factor kappaB pathway. J. Periodontal Res. 38, 557-563 72. Yadav, M., and Schorey, J. S. (2006) The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood 108, 3168-3175 73. Katilius, E., Flores, C., and Woodbury, N. W. (2007) Exploring the sequence space of a DNA aptamer using microarrays. Nucleic Acids Res. 35, 7626-7635 74. Haylett, D. G. (2003) Direct measurement of drug binding to receptors. In Textbook of Receptor Pharmacology, 2nd edition. (Foreman, J. C., and Johansen, T., eds) pp. 153-180, CRC Press LLC, Boca Raton, USA. 75. Abrahams, V. M., Bole-Aldo, P., Kim, Y. M., Straszewski-Chavez, S. L., Chaiworapongsa, T., Romero, R., Mor, G. (2004) Divergent trophoblast responses to bacterial products mediated by TLRs. J. Immunol. 173, 4286-4296 76. Triantafilou, M., Gamper, F. G., Haston, R. M., Mouratis, M. A., Morath, S., Hartung, T., Triantafilou, K. (2006) Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting. J. Biol. Chem. 281, 31002-31011 77. Nagai, Y., Akashi, S., Nagafuku, M., Ogata, M., Iwakura, Y., Akira, S., Kitamura, T., Kosugi, A., Kimoto, M., Miyake, K. (2002) Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat.Immunol. 3, 667-672 第二部分 1. Ogston, A. (1844-1929) Classics in infectious diseases. 'On abscesses'.Rev.Infect.Dis. 6, 122-128 2. Scott, W. J. (1953) Water relations of Staphylococcus aureus at 30 degrees C.Aust.J.Biol.Sci. 6, 549-564 3. Chow, A. W., Gribble, M. J., Bartlett, K. H. (1983) Characterization of the hemolytic activity of taphylococcus aureus strains associated with toxic shock syndrome. J.Clin.Microbiol. 17, 524-528 4. Clyne, M., De, A. J., Carlson, E., Arbuthnott, J. (1988) Production of gamma-hemolysin and lack of production of alpha-hemolysin by Staphylococcus aureus strains associated with toxic shock syndrome. J.Clin.Microbiol. 26, 535-539 5. Millar, M., Wilcock, A., Sanderson, Y., Kite, P., McDonnell, M. K. (1986) Catalase negative Staphylococcus aureus. J.Clin.Pathol. 39, 695 6. Lominski, I., Grossfeld, E. (1948) An improved direct coagulase test for the rapid detection of Staphylococcus aureus. Br.Med.J. 1, 343 7. Langlet, S., Quentin, G., Contant, G., Ghnassia, J. C. (1999) [A chromogenic method for rapid identification of Staphylococcus aureus]. Ann.Biol.Clin.(Paris) 57, 191-196 8. Rappaport, T., Sawyer, K. P., Nachamkin, I. (1988) Evaluation of several 47 commercial biochemical and immunologic methods for rapid identification of gram-positive cocci directly from blood cultures. J.Clin.Microbiol. 26, 1335-1338 9. Lowy, F. D. (1998) Staphylococcus aureus infections. N.Engl.J.Med. 339, 520-532 10. Kluytmans, J., van, B. A., Verbrugh, H. (1997) Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin.Microbiol.Rev. 10, 505-520 11. Swartz, M. N. (1994) Hospital-acquired infections: diseases with increasingly limited therapies. Proc.Natl.Acad.Sci.U.S.A 91, 2420-2427 12. Reygaert, W. (2009) Methicillin-resistant Staphylococcus aureus (MRSA): prevalence and epidemiology issues. Clin.Lab Sci. 22, 111-114 13. Wells, R. D., Mason, P., Roarty, J., Dooley, M. (2009) Comparison of initial antibiotic choice and treatment of cellulitis in the pre- and post-community-acquired methicillin-resistant Staphylococcus aureus eras. Am.J.Emerg.Med. 27, 436-439 14. Kapral, F. A., Godwin, J. R., Dye, E. S. (1980) Formation of intraperitoneal abscesses by Staphylococcus aureus. Infect.Immun. 30, 204-211 15. Robertson, L., Caley, J. P., Moore, J. (1958) Importance of Staphylococcus aureus in pneumonia in the 1957 epidemic of influenza A. Lancet 2, 233-236 16. Gordon, J. J., Harter, D. H., Phair, J. P. (1985) Meningitis due to Staphylococcus aureus. Am.J.Med. 78, 965-970 17. Jeffery, C. C., Sevitt, S., Topley, E. (1949) Acute osteomyelitis due to a penicillinase-producing Staphylococcus aureus. Lancet 1, 259-261 18. Phair, J. P., Tan, J. S., Watanakunakorn, C., Schiff, G. M. (1971) Staphylococcus aureus endocarditis. J.Lab Clin.Med. 78, 984-985 19. Cross, A. S., Zierdt, C. H., Roup, B., Almazan, R., Swan, J. C. (1983) A hospital-wide outbreak of septicemia due to a few strains of Staphylococcus aureus. Am.J.Clin.Pathol. 79, 598-603 20. Klein, E., Smith, D. L., Laxminarayan, R. (2007) Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg.Infect.Dis. 13, 1840-1846 21. Eriksen, K. R. (1961) ['Celbenin'-resistant staphylococci.]. Ugeskr.Laeger 123, 384-386 22. Washer, P., Joffe, H. (2006) The 'hospital superbug': social representations of MRSA. Soc.Sci.Med. 63, 2141-2152 23. Richmond, M. H. (1979) Beta-lactam antibiotics and beta-lactamases: two sides of a continuing story. Rev.Infect.Dis. 1, 30-38 24. Cheng, J. C., Huang, C. L., Lin, C. C., Chen, C. C., Chang, Y. C., Chang, S. S., Tseng, C. P. (2006) Rapid detection and identification of clinically important bacteria by high-resolution melting analysis after broad-range ribosomal RNA real-time PCR. Clin.Chem. 52, 1997-2004 25. Moore, D. F., Curry, J. I. (1998) Detection and identification of Mycobacterium tuberculosis directly from sputum sediments by ligase chain reaction. J.Clin.Microbiol. 36, 1028-1031 26. Edman, C. F., Mehta, P., Press, R., Spargo, C. A., Walker, G. T., Nerenberg, M.(2000) Pathogen analysis and genetic predisposition testing using microelectronic arrays and isothermal amplification. J.Investig.Med. 48, 93-101 27. Swaminathan, B., Feng, P. (1994) Rapid detection of food-borne pathogenic bacteria. Annu.Rev.Microbiol. 48, 401-426 28. Huang, S. H., Chang, T. C. (2004) Detection of Staphylococcus aureus by a sensitive immuno-PCR assay. Clin.Chem. 50, 1673-1674 29. Tuerk, C., Gold, L. (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249, 505-510 30. Ellington, A. D., Szostak, J. W. (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346, 818-822 31. Bock, L. C., Griffin, L. C., Latham, J. A., Vermaas, E. H., Toole, J. J. (1992) Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature 355, 564-566 32. Zuo, X., Xiao, Y., Plaxco, K. W. (2009) High specificity, electrochemical sandwich assays based on single aptamer sequences and suitable for the direct detection of small-molecule targets in blood and other complex matrices. J.Am.Chem.Soc. 131, 6944-6945 33. Chang, Y. C., Kao, W. C., Wang, W. Y., Wang, W. Y., Yang, R. B., Peck, K. (2009) Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses. FASEB J. In Press. 34. Lin, Y., Jayasena, S. D. (1997) Inhibition of multiple thermostable DNApolymerases by a heterodimeric aptamer. J.Mol.Biol. 271, 100-111 35. Farokhzad, O. C., Cheng, J., Teply, B. A., Sherifi, I., Jon, S., Kantoff, P. W., Richie, J. P., Langer, R. (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc.Natl.Acad.Sci.U.S.A 103, 6315-6320 36. Lee, H. J., Kim, B. C., Kim, K. W., Kim, Y. K., Kim, J., Oh, M. K. (2009) A sensitive method to detect Escherichia coli based on immunomagnetic separation and real-time PCR amplification of aptamers. Biosens.Bioelectron. In Press. 37. Chen, F., Zhou, J., Luo, F., Mohammed, A. B., Zhang, X. L. (2007) Aptamer from whole-bacterium SELEX as new therapeutic reagent against virulent Mycobacterium tuberculosis. Biochem.Biophys.Res.Commun. 357, 743-748 38. Joshi, R., Janagama, H., Dwivedi, H. P., Senthil Kumar, T. M., Jaykus, L. A., Schefers, J., Sreevatsan, S. (2009) Selection, characterization, and application of DNA aptamers for the capture and detection of Salmonella enterica serovars. Mol.Cell Probes 23, 20-28 39. Zhen, B., Song, Y. J., Guo, Z. B., Wang, J., Zhang, M. L., Yu, S. Y., Yang, R. F. (2002) [In vitro selection and affinity function of the aptamers to Bacillus anthracis spores by SELEX]. Sheng Wu Hua Xue.Yu Sheng Wu Wu Li Xue.Bao.(Shanghai) 34, 635-642 40. Yguerabide, J., Yguerabide, E. E. (1998) Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications. Anal.Biochem. 262, 137-156 41. Li, Z. P., Duan, X. R., Liu, C. H., Du, B. A. (2006) Selective determination of cysteine by resonance light scattering technique based on self-assembly of gold nanoparticles. Anal.Biochem. 351, 18-25 42. Nam, J. M., Thaxton, C. S., Mirkin, C. A. (2003) Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science 301, 1884-1886 43. Waitz, J. A., Doern, G. V., Finegold, S. M., Gaven, T. L., Hackett, J. L., Jones, R. N., Jorgensen, J. H., King, J. R., Miller, G. H., Reller, L. B., Thornsberry, C., Thrupp, L. D., Zabransky, R. J. (1990) Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically - Second Edition. NCCLS 10, M7-A2 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42618 | - |
| dc.description.abstract | 適體 (Aptamer) 泛指一種DNA 或RNA 的核酸分子結構，可因內含序列的不同而形成多樣的立體結構並結合相對應之目標分子。 適體分子可利用PCR 技術進行分子數之放大，而利用反覆與目標物結合，分離及放大的適體篩選技術(SELEX， Systematic evolution of ligands by exponential enrichment)，專一性的適體分子可以完全以試管實驗 (In vitro)的步驟篩選出來，相對於單株抗體需要動物或大量的融合瘤細胞來製造，適體的篩選明顯方便許多。 因此自從90 年代初期發現適體具有類似抗體的特性後，許多針對不同目標物的適體分子便接連被分離且發表，其中某些適體分子更具有調節蛋白質或細胞活性之功能。 除此之外，許多報告更將適體應用於化學分子，蛋白質，或癌細胞檢測上。本論文研究主要分成兩個部分，第一部分的研究專注於將適體分子應用於免疫系統的調節上。 研究過程中，成功的建立了一個名為IP-SELEX 技術，此技術成功的將傳統SELEX 的步驟簡化並縮短篩選的時間至兩個星期內。利用IP-SELEX，成功的篩選出專一性結合TLR2 接受器 (為一調控先天免疫反應的接
受器) 的適體分子，而其中某些適體分子更具有調節TLR2 相關免疫反應之功能。此外本論文也應用基因微陣列技術(DNA microarray)於快速分析與TLR2 結合之適體分子序列上。此部分的研究完整的包含了篩選技術的建立、TLR2 適體分子的篩選、適體分子的分析及鑑定、一直到適體分子的應用。第二部份的研究主要針對如何將適體分子應用於高敏感度的細菌檢測上。利用全細胞篩選技術 (Cell-based SELEX)，專一性結合金黃色葡萄球菌的適體分子被成功的分離出來，並進行專一性測試。 本研究進一步將所分離的適體分子與奈米金粒子結合，並利用奈米金粒子對光產生的強共振散射特性，建立了一個平台技術，此技術可在1.5 小時內檢測微量金黃色葡萄菌的存在，並且達到接近PCR 技術的偵測敏感度。 同時也利用這個檢測平台，成功的將抗生素檢定的時間由傳統的16 小時以上縮短至3 小時內。綜合而言，本論文研究成功地將適體分子應用於免疫系統的調節及高敏感度病原體檢測上，而這個研究也說明了適體分子不論在學術研究或臨床應用上都具有極高的潛力。 | zh_TW |
| dc.description.abstract | Aptamers are DNA or RNA molecules capable of folding into a variety of structures based on their sequence compositions. Like antibody, aptamers can specifically bind to their target molecules with nano- to pico-molar range of dissociation constant. However, aptamers possess several advantages over monoclonal antibodies. For examples, aptamers are stable in a wide range of temperatures and pH values, and they can be easily amplified by PCR or produced by chemical synthesis. Moreover, aptamers for a particular protein are identified with a technology called SELEX
(Systematic Evolution of Ligands by EXponential enrichment) operated totally in vitro and the process can be automated. For these reasons, since the discovery of aptamers in early 1990’s, numerous aptamer sequences have been identified to interact with a wide range of targets from as small as antibiotics to as large as mammalian cells. Some of the aptamers even exhibit capability to regulate the biochemical function of their targets. On the other hand, aptamers had also been applied in detection of small chemical compounds, proteins, or cancer cells. This dissertation is composed of two parts. The first part focuses on identifying the immune-regulatory aptamers. Toll-like receptor 2 was selected as a model, for its important role in regulating innate immune system. In this study, an advanced selection method called IP-SELEX was developed, which simplified the traditional SELEX protocols and reduced the time for aptamer selection to within two weeks. Moreover, high affinity TLR2 aptamers were isolated and characterized. The antagonistic aptamers were identified by using large-scale functional screening and analyzed for its binding domain by using high throughput DNA microarray. This dissertation is a complete report including development of IP-SELEX method, isolation and characterization of TLR2 aptamers, and application of the isolated aptamers. The second part of the dissertation focuses on applying DNA aptamer in ultrasensitive pathogen detection. In this study, aptamers specifically targeted Staphylococcus aureus were isolated with cell-based SELEX. The isolated aptamers were conjugated with gold nanoparticles for S. aureus detection. The instrument that detects resonance light scattering signal of gold nanoparticles is constructed. The system can reach PCR-like sensitivity within 1.5 hr. Moreover, the technology is also applied in antimicrobial susceptibility testing to reduce the required time span from 16 hr to 3 hr. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:17:52Z (GMT). No. of bitstreams: 1 ntu-98-D91445005-1.pdf: 5506984 bytes, checksum: 27522dbd79d672c761e51000c7cd6955 (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 中 文 摘 要 I
ABSTRACT . III ABBREVIATIONS FOR PART I .. V ABBREVIATIONS FOR PART II .. VI CONTENTS . . VII PART I TITLE .. 1 1.1. 第一部分中文摘要 2 1.2. ABSTRACT OF PART I . 4 1.3. INTRODUCTION .6 1.3.1. Introduction of Toll-like receptors. . 6 1.3.2. Ligands for Toll-like receptors. .. 7 1.3.3. The role of Toll-like receptors in innate and adaptive immune system .. . 7 1.3.4. Toll-like receptors and human diseases. 8 1.3.4.1. Toll-like receptors and dysregulated immune responses . .. 8 1.3.4.2. Toll-like receptors and autoimmune diseases . . 9 1.3.4.3. Toll-like receptors and cancer. . 9 1. 3.5. Introduction of aptamer .. 10 1.3.6. Synopsis of the study .. 11 1.4. SPECIFIC AIMS 13 1.5. MATERIALS AND METHODS .. .15 1.5.1. Cell lines and reagents .. .15 1.5.2. Primers and aptamers ..16 1.5.3. Plasmid construction and TLR2-Fc expression . 17 1.5.4. Immunoprecipitation-SELEX (IP-SELEX) ..17 1.5.5. Screening TLR2 antagonistic aptamers by NF-κB reporter assay .18 1.5.6. Confocal fluorescence imaging ..19 1.5.7. TLR2 knockdown by lentiviral RNAi . .20 1.5.8. Aptamer microarray for identifying the binding region of the TLR2 aptamer. .21 1.5.9. Cytokine analysis for functional aptamers .21 1.5.10. Measuring dissociation constants of TLR2 aptamers .22 1.5.11. Binding assay for ssDNA pools and aptamers isolated from IP-SELEX ..23 1.5.12. Flow cytometric analysis of aptamer specificity . 23 1.5.13. Acute sepsis model in balb/c mice . 24 6. RESULTS . 25 1.6.1. DNA aptamers against human TLR2 . .. 25 1.6.2. Functional aptamers of TLR2 . . 26 1.6.3. The specificity of AP177 for TLR2 . . 28 1.6.4 Resolving the aptamer binding region by microarray analysis 29 1.6.5 AP177 inhibits TLR2 activation by agonistic ligands other than SA-LTA .. 32 1.6.6 AP177 protects balb/c mice from B. subtilis induced septic shock .. 33 7. DISCUSSION . 35 1.7.1. The advantages of IP-SELEX . 35 1.7.2. Antagonistic TLR2 aptamer was identified .. . 37 1.7.3. AP177 and other TLR2 agonists . . 38 1.7.4. AP177 and TLR9 .. 39 1.7.5. Microarray could be a power tool in aptamer analysis . 40 1.7.6. The variation between dissociation constant and IC50 . 41 1.7.7. Conclusion .. . 42 TABLES OF PART I 44 FIGURES OF PART I . 45 REFERENCES OF PART I .66 APPENDIX OF PART I .. 78 PART II TITLE .. 106 2.1.第二部分中文摘要 ..107 2.2. ABTRACT OF PART II .109 2.3. INTRODUCTION ..110 2.3.1. Introduction of S. aureus .. .110 2.3.2. S. aureus and human diseases 110 2.3.3. Introduction of MRSA. . 111 2.3.4. Bacterial identification methods used in clinical laboratory ..112 2.3.5. Aptamer for bacteria detection .112 2.3.6. Introduction of gold nanoparticles 113 2.3.7. Synopsis of the study 114 2.4. SPECIFIC AIMS .116 2.5. MATERIALS AND METHODS .118 2.5.1. Primers and aptamers ..118 2.5.2. Cell-based SELEX ..118 2.5.3. Bacterial cultures and harvest condition 119 2.5.4. Dissociation constant measurement for SA aptamers .120 2.5.5. Immunofluorescence assay ..120 2.5.6. Conjugation of gold nanoparticles . .121 2.5.7. Aptamer-GNPs for S. aureus detection .122 2.5.8. Scanning electron microscope ..123 2.5.9. Antimicrobail susceptibility testing . .123 2.6. RESULTS .125 2.6.1. Cell-base selection of aptamers against S. aureus .125 2.6.2. Aptamers specifically recognized S. aureus 125 2.6.3. Dissociation constant, structure and binding capacity of SA17 and SA61 126 2.6.4. Resonance light-scattering signal of different sizes and concentrations of GNPs . ..127 2.6.5. Interaction of aptamer-conjugated GNPs with S. aureus .127 2.6.6. Nano-bead amplification in detection of S. aureus . .128 2.6.7 Aptamer-GNPs for rapid antimicrobial susceptibility testing. .129 2.7. DISCUSSION . . .131 2.7.1. The strategy for cell-based SELEX against S. aureus ..131 2.7.2. The specificity of SA17 and SA61 . . .132 2.7.3. Aptamer- a good tool for pathogen detection .132 2.7.4. Aptamer- GNPs in ultrasensitive pathogen detection ..133 2.7.5. Aptamer- GNPs in antimicrobial susceptibility testing ..134 2.7.6. Conclusion 135 TABLES OF PART II .. 137 FIGURES OF PART II 139 REFERENCES OF PART II ..155 APPENDIX OF PART II .161 | |
| dc.language.iso | en | |
| dc.subject | TLR 接受器 | zh_TW |
| dc.subject | 奈米金 | zh_TW |
| dc.subject | 金黃色葡萄球菌 | zh_TW |
| dc.subject | 發炎反應 | zh_TW |
| dc.subject | IP-SELEX | zh_TW |
| dc.subject | 適體 | zh_TW |
| dc.subject | aptamer | en |
| dc.subject | gold nanoparticles | en |
| dc.subject | bacterial detection | en |
| dc.subject | IP-SELEX | en |
| dc.subject | microbial infection | en |
| dc.subject | antagonist | en |
| dc.title | DNA 適體於免疫治療及微生物檢測上之應用研究 | zh_TW |
| dc.title | Novel applications of DNA aptamer in immune regulation and
pathogen detection | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 楊瑞彬(Ruey-bing Yang),楊淑美(Shu-Mei Liang),廖楓(Fang Liao),陳林祈(Lin-Chi Chen) | |
| dc.subject.keyword | 適體,TLR 接受器,IP-SELEX,發炎反應,金黃色葡萄球菌,奈米金, | zh_TW |
| dc.subject.keyword | aptamer,antagonist,microbial infection,IP-SELEX,bacterial detection,gold nanoparticles, | en |
| dc.relation.page | 163 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2009-07-27 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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