現代質譜法，基質輔助雷射脫附游離飛行時間質譜（ matrix-assisted laser desorption ionization/time of flight mass spectrometry，MALDI-TOF/MS）具有分析快速、操作簡單、樣品需求量少，高靈敏度及可以自動化的優勢，相當適合應用於疾病生物指標（biomarker）的快速搜尋及分子影像（molecular imaging）的分析。
本研究的第一部分即以基質輔助雷射脫附游離飛行時間質譜法結合酸水解技術快速偵測20位重憂鬱症及20位控制組的血清中組成，實驗發現血清樣品經過酸水解處理後，可把血清中主要蛋白質中的白蛋白干擾去除，使得其他較微量的蛋白質可以被觀察到。經由本研究方法可直接獲得在血清中分別屬於正向急性蛋白的纖維蛋白（Fibrinogen）和負向急性蛋白的運鐵蛋白（Transferrin）經酸水解後的片斷分別為 m/z 9287及 m/z 8606，將此兩訊號的面積相除(運鐵蛋白/纖維蛋白) 所得到的值在重憂鬱症患者為1.02 ± 0.52，而在控制組為3.58 ± 1.93，在重憂鬱症患者及控制組血清中組成有不同的表現，由此結果推論運鐵蛋白及纖維蛋白可成為快速診斷重憂鬱症的新疾病生物指標。
研究的第二部分為將基質輔助雷射脫附游離飛行時間質譜法應用於搜尋並快速篩檢缺血性中風病人的診斷指標，實驗的進行為將血清樣品經純水稀釋再將樣品與MALDI基質混合形成共結晶後，以質譜儀分析之後統計了84個樣品的結果(包括50個中風病人和34個控制組)，結果發現在中風病人的血清中，50個病人檢體可觀察到hemoglobin的訊號，其比例高達72 ％；控制組部分在34個人中僅有5個人在質譜圖中發現有hemoglobin的訊號，其比例為14.7 ％。經ROC 曲線（receiver operating characteristic curve）評估血清中hemoglobin做為缺血性中風的生物指標其靈敏度和特異度分別為72% 和 85.3%，此結果獲得的診斷準確度相對於目前文獻報導的中風指標來得高。
第三部分的研究為以基質輔助雷射脫附游離飛行時間質譜法來探討α-防禦素1-3（α-defensin 1-3）這種與身體免疫機制有關抗菌多肽在各式體液中分佈的狀況。實驗顯示眼球前房液、鼻水、胸水、膽汁未觀察到α-防禦素1-3的訊號，口水、胃液及子宮抹片液體則有α-防禦素1-3的訊號，此外在實驗中觀察到當眼睛經過外科手術後的眼淚樣品相較於正常人的樣品α\\\\-防禦素1-3訊號有局部大量表現的情況，推測這是因為當生物體面對（如外科開刀）此種會引起重大免疫反應會使得與免疫機制有關的防禦素大量表現，而且α-防禦素1-3可以做為區分乾眼症病人及正常人眼淚的指標，此外也觀察到在小孩誕生三個月內的母奶中有α\\\\-防禦素1-3的訊號，這可能是母奶中提供給新生嬰兒先天免疫能力的來源。
第四部分的研究為基質輔助雷射脫附游離飛行時間質譜結合分子影像分析系統，相較於傳統的均勻化的分析，結合影像的研究提供了所在位置的資訊，本研究即將此技術應用於獸醫醫學、癌症醫學及海洋生物學：包括1.家畜傳染病的研究:於新城雞瘟與正常白肉雞的腦部組織中找到區分新城雞瘟的指標m/z 7329 ，m/z 8577；2. 癌症指標的搜尋:於正常及癌變的組織樣品(包括人類食道癌、胃癌及攝護腺癌) 找到可能的癌症指標m/z 3278， m/z 3380， m/z 3450；3.珊瑚白化機制的探討:分析了正常珊瑚及白化的珊瑚組織結果發現m/z 3204、m/z 2919、m/z 2757這些訊號主要分佈於珊瑚本身的訊息，m/z 932，m/z 909，m/z 871則來自共生藻，藉由這些分子分佈的情形探討珊瑚白化的發生。

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目錄
論文摘要....................................................................................................i
目錄...........................................................................................................iii
圖目錄…………………………………………………...……………....vi
表目錄…………………………………………………...……………..xvi
壹、緒論...................................................................................................1
一﹒質譜發展史.…………. ……………………………………………1
二、MALDI-TOF MS介紹.………….…………………………….……6
三、精神疾病與其生物指標 .…………………………………….……13
四、缺血性中風指標…………………………………………….….....17
五、抗菌胜肽與動物的免疫作用……………………………………....18
六、影像質譜法與生物指標………………………………………...….21
七、論文目標…………………………………….…………….……….21貳、以現代質譜法搜尋精神疾病的生物指標. ... .................................23
一、研究目標………………………………..........................................23
二、研究背景..........................................................................................24
三、精神疾病的介紹..............................................................................24
(一)、精神疾病分類的方式…………………………………..……….25
(二)、精神疾病發生原因的假說與用藥…………….……….……….27
四、實驗部分……………………………………………..……………35
(一)、儀器與藥劑..............................................................................35
(二)、精神疾病病人之篩選……………………………...………..37
五、結果與討論................................................................................37
六、結論............................................................................................64
參、以現代質譜法搜尋及快速篩選急性缺血性中風的生物指標........65
一、研究目標………………………………...........................................65
二、研究背景...........................................................................................65
三、中風介紹...........................................................................................66
四、實驗部分………………………………………………..…..………67
五、結果與討論......................................................................................68
六、結論..................................................................................................77
肆、現代質譜法應用於α-defensins 於人體體液中分佈狀況的探討...78
一、研究目標………………………………...........................................78
二、研究背景..........................................................................................78
三、防禦素(defensin)介紹.....................................................................80
四、乾眼症介紹....................................................................................86
五、實驗部分……………………………………………..……………89
六、結果與討論.....................................................................................89
七、結論.................................................................................................95
伍、影像質譜法（Imaging Mass Spectrometry）..............................97
一、前言………………………………...............................................97
二、新城病簡介.................................................................................123
三、珊瑚礁與珊瑚白化.....................................................................126
四、實驗部分.....................................................................................132
五、結果與討論............................................................................. …133
(一)、MALDI Imaging應用於腦組織的分析...................................134
(二)、MALDI Imaging應用於海洋生物學的分析...........................143
(三)、MALDI Imaging應用於癌症醫學的研究:攝護腺癌及胃癌..... 149
六、結論................................................................................................153
陸、結論.................................................................................................154
柒、參考資料........................................................................................156

1. Thomson, J. J. “On Rays of Positive Electricity” Phil. Mag. Series. 1907, 13, 561.
2. Aston F, W.”The Mass-Spectra of Chemical Elements” Phil. Mag. 1919, XXXVIII, 707.
3. Mattauch, J.; Herzog, R.”Über einen neuen Massenspektrographen” Z Phys A At Nucl. 1934, 89, 786.
4. Stephens, W. “Pulsed Mass Spectrometer with Time Dispersion”
Bull. Am. Phys. Soc., 1946, 21, 22.
5. Smith, L.P.; Parkins, W.E.; Forrester, A.T.”On the Separation of Isotopes in Quantity by Electromagnetic Means” Phys. Rev., 1947, 72, 989.
6. Hipple, J.A.; Sommer, H.; Thomas, H.A.”A Precise Method of Determining the Faraday by Magnetic Resonance” Phys. Rev., 1949, 76, 1877.
7. Paul, W.; Steinwedel, H.”Ein neues Massenspektrometer ohne Magnetfeld” Z. Naturforschg. 1953, 8, 448.
8. Castaing, R.; Slodzian, G. “Microanalysis by secondary ion emission” J Microsc . 1962, 1, 395.
9. Munson, M. S. B.; Field, F. H. “Chemical Ionization Mass Spectrometry. I. General Introduction.” J. Am. Chem. Soc. 1966, 88,2621.
10. Jennings, K.R.”Collision-Induced Decompositions of Aromatic Molecular Ions” Int. J. Mass Spec. Ion Physics. 1968, 1, 227.
11. Hipple, J.A.; Sommer, H.; Thomas, H. A.”A Precise Method of Determining the Faraday by Magnetic Resonance” Phys. Rev. 1949, 76, 1877.
12. Carroll, D.I.; Dzidic, I.; Stillwell, R.N.; Haegele, K.D.; Horning, E.C.
“Atmospheric Pressure Ionization Mass Spectrometry: Corona Discharge Ion Source for Use in Liquid Chromatograph - Mass Spectrometer - Computer Analytical System” Anal. Chem.. 1975, 47, 2369.
13. Yost, R.A.; Enke, C.G.”Selected Ion Fragmentation with a Tandem Quadrupole Mass Spectrometer” J. Am. Chem. Soc.1978, 100, 2274.
14. Karas, M.; Bachmann D.; Hillenkamp, F. “Influence of the Wavelength in High-Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules” Anal. Chem. 1985, 57, 2935.
15. Tanaka, K.; Waki, H.; Ido, Y.; Akita, S.; Yoshida Y.; Yoshida, T. “Protein and Polymer Analysis up to m/z 100,000 by Laser Ionization Time-of-Flight Mass Spectrometry ”Rapid Commum. Mass Spectrom. 1988, 2, 151.
16. Karas, M.; Hillenkamp, F. “Laser Desorption Ionization of Proteins with Mloecular Masses Exceeding 10,000 Daltons” Anal. Chem.1988, 60, 2299.
17. Nelson, R. W.; Dogruel, D.; Williams, P. “Mass Determination of Human Immunoglobulin IgM Using Matrix-Assisted Laser Desorption / Ionization Time-of-Flight Mass Spectrometry” Rapid Commum. Mass Spectrom. 1994, 8, 627.
18. Van Breemen , R. B.; Snow, M.; Cotter, R. J. “Time-Resolved Laser Desorption Mass Spectrometry. Desorption of Performed Ions”Int. J. Mass. Spectrom. Ion. Phys. 1983, 49, 35.
19. Ehring, H.; Karas, M.; Hillenkamp, F. “Role of Photoionization and Photochemistry in Ionization Processes of Organic-Molecules and Relevance for Matrix-Assisted Laser Desorption Ionization Mass-Spectrometry”Org. Mass Spectrom. 1992, 27, 472.
20. Bahr. U.; Karas, M.; Hillenkamp, F.; Fresenius, J. “Analysis of Biopolymers by Matrix-Assisted Laser Desorption / Ionization Mass Sepectrometry” Anal. Chem. 1994, 66, 783.
21. Ehring, H.; Karas, M.; Hillenkamp, F. “Role of Photoionization and Photochemistry in Ionization Processes of Organic-Molecules and Relevance for Matrix-Assisted Laser Desorption Ionization Mass Spectrometry” Org. Mass Spectrom. 1992, 27, 472.
22. Juhasz, P.; Costello, C. E.; Biemann, K. “Matrix-Assisted Laser Desorption Ionization Mass-Spectrometry with 2-(4-Hydroxyphenyl-azo)benzoic acid Matrix” J. Am. Chem. Soc. Mass Spectrom. 1993, 4, 399.
23. Fitzgerald, M. C.; Parr, G. R.; Smith, L. M. “Basic Matrices for Matrix- Assisted Laser Desorption / Ionization Mass Spectrometry of Protein Oligonucleotides” Anal. Chem. 1993, 65, 3204
24. Dole, M.; Mack, L. L.; Hines, R. L. “Molecular Beams of Macroions”J. Chem. Phys. 1968, 49, 2240.
25. Ehring, H.; Karas, M.; Hillenkamp, F. “Role of Photoionization and Photochemistry in Ionization Processes of Organic-Molecules and Relevance for Matrix-Assisted Laser Desorption Ionization Mass Spectrometry” Org. Mass Spectrom. 1992, 27, 472.
26. Mack, L. L.; Kralic, P.; Rheude, A.; Dole, M. “Molecular Beams of Macroions Part II” J. Chem. Phys. 1970, 52, 4977.
27. Yamashita, M.; Fenn, J. “Electrospray Ion Source. Another Variation on the Free-Jet Theme” J. Phys. Chem. 1984, 88, 4451.
28. Wong, S. F.; Meng, C. K.; Fenn, J. B. “Mutiple Charging Inelectrospray Ionization for Poly(ethylene glycols)”J. Phys. Chem. 1988, 92, 546.
29. Meng, C. K.; Mann, M.; Fenn, J. B. “OfProtons or Proteins – A Beams A Beam for A That”Z. Phys. D. 1988, 10, 361.
30. Yamashita, M.; Fenn, J. B. “Negative Ion Production with the Electrospray Ion Source” J. Phys. Chem. 1984, 88, 4671.
31. Fenn, J. B.; Mann, M.; Meng, C. K.; Wong, S. F.; Whitehouse, C. M. ”Electrospray Ionization for Mass Spectrometry of Large Biomolecules”Science 1989, 246, 64.
32. Glish, G.L.; Goeringer, D.E.”Tandem Quadrupole/Time-of-Flight Instrument for Mass Spectrometry/Mass Spectrometry” Anal. Chem. 1984, 56, 2291.
33. Spengler, B.; Kirsch, D.; Kaufmann, R.”Metastable Decay of Peptides and Proteins in Matrix-Assisted Laser-Desorption Mass Spectrometry” Rapid Commum. Mass Spectrom. 1991, 5, 198.
34. Makarov, A.”Electrostatic Axially Harmonic Orbital Trapping: A High-Performance Technique of Mass Analysis “Anal. Chem. 2000, 72, 1156.
35. Hong, C. M.; Tsai, F. C.; Shiea, J. “A Multiple Channel Electrospray Source Used to Detect Highly Reactive Ketenes from A Flow Pyrolyzer” Anal. Chem. 2000, 72, 1175.
36. Hsu, H. J.; Kuo, T. L.; Wu, S. H.; Oung, J. N.; Shiea, J. “Characterization of Synthetic Polymers by Electrospray-Assisted Pyrolysis Ionization Mass Spectrometry” Anal. Chem. 2005, 77,7744.
37. Hsu, H. J.; Oung, J. N.; Kuo, T. L.; Wu, S. H.; Shiea, J “Using Electrospray-Assisted Pyrolysis Ionization / Mass Spectrometry for the Rapid Characterization of Trace Polar Components in Crude Oil, Amber, Humic Substances, and Rubber Samples” Rapid Commun. Mass Spectrom. 2007, 21, 375.
38. Takats, Z.; Wiseman, J. M.; Gologan, B.; Cooks, R. G. “Mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization”Science. 2004, 306, 471.
39. Takats, Z.; Wiseman, J. M.; Cooks, R. G. “Ambient Mass Spectrometry Using Desorption Electrospray Ionization (DESI): Instrumentation, Mechanisms and Applications in Forensics,Chemistry, and Biology”J. Mass Spectrom. 2005, 40, 1261.
40. Cotte-Rodriguez, I.; Takats, Z.; Talaty, N.; Chen, H.; Cooks, R. G.,“Desorption Electrospray Ionization of Explosives on Surfaces: Sensitivity and Selectivity Enhancement by Reactive Desorption Electrospray Ionization”Anal. Chem. 2005, 77, 6755.
41. Venter, A.; Sojka, P. E.; Cooks, R. G. “Droplet Dynamics and Ionization Mechanisms in Desorption Electrospray Ionization Mass Spectrometry” Anal. Chem. 2006, 78, 8549.
42. Cooks, R. G.; Ouyang, Z.; Takas, Z.; Wiseman, J. M. “Ambient Mass Spectrometry”Science. 2006, 311, 1566.
43. Van. Berkel, G. J.; Ford, M. J.; Deibel, M. ”Thin-Layer Chromatography and Mass Spectrometry Coupled Using Desorption Electrospray Ionization”Anal. Chem. 2005, 77, 1207.
44. Cotte-Rodriguez, I.; Cooks, R. G. “Non-Proximate Detection of Explosives and Chemical Warfare Agent Simulants by Desorption Electrospray Ionization Mass Spectrometry”Chem. Commun. 2006, 2968.
45. Justes, D. R.; Talaty, N.; Cotte-Rodriguez, I.; Cooks, R. G. “Detection of Explosives on Skin Using Ambient Ionization Mass Spectrometry”Chem. Commun. 2007, 2142.
46. Takats, Z.; Rodriguez, I. C.; Talaty, N.; Chen, H.; Cook, R. G.“Direct Trace Level Detection of Explosives on Ambient Surfaces by Desorption Electrospray Ionization Mass Spectrometry”Chem. Commun. 2005, 1950.
47. Song, Y.; Cook, R. G. “Atmospheric Pressure Ion / Molecule Reactions for the Selective Detection of Nitroaromatic Explosives Using Acetonitrile and Air as Reagents”Rapid. Commun. Mass Spectrom. 2006, 20, 3130.
48. Cody, R. B.; Laramee , J. A.; Durst , H. D. “Versatile New Ion Source for the Analysis of Materials in Open Air under Ambient Conditions”Anal. Chem. 2005, 77, 2297.
49. Cody, R. B.; Laramee , J. A.; Nilles, J. M.; Durst , H. D. “Direct Analysis in Real Time (DART) Mass Spectrometry”JEOL News 2005, 40, 8.
50. Fernadez, F. M.; Cody, R. B.; Green, M. D.; Hampton, C. Y.; McGready, R.; Sengaloundeth, S.; White, N. J.; Newton, P. N. “Characterization of Solid Counterfeit Drug Samples by Desorption Electrospray Ionization and Direct-Analysis-in-Real-Time Coupled to Time-of-Flight Mass Spectrometry”Chem. Med. Chem. 2006, 1, 702.
51. Pierce, C. Y.; Barr, J. R.; Cody, R. B.; Massung, R. F.; Woolfitt, A. R.; Moura, H.; Thompson, H. A.; Fernandez, F. M. “Ambient Generation of Fatty Acid Methyl Ester Ions from Bacterial Whole Cells by Direct Analysis in Real Time (DART) Mass Spectrometry” Chem. Commun. 2007, 807.
52. Morlock, G.; Ueda, Y. “New Coupling of Planar Chromatography with Direct Analysis in Real Time Mass Spectrometry” J. Chromatogr. A 2007, 1143, 243.
53. Haefliger, O. P.; Jeckelmann, N. “Direct Mass Spectrometric Analysis of Flavors and Fragrances in Real Applications Using DART”Rapid Commun. Mass Spectrom. 2007, 21, 1361.
54. McEwen, C. N.; McKay, R. G.; Larsen, B. S.; “Analysis of Solids, Liquids, and Biological Tissues Using Solids Probe Introduction at Atmospheric Pressure on Commercial LC / MS Instruments”Anal. Chem. 2005, 77, 7826.
55. Sampson, J. S.; Hawkridge, A. M.; Muddiman, D. C. “Generation and Detection of Multiply Charged Peptides and Proteins by Matrix-Assisted Laser Desorption Electrospray Ionization (MALDESI) Fourier Transform Ion Cyclotron Resonance Mass Spectrometry”J. Am. Soc. Mass Spectrom. 2006, 17, 1712.
56. Sampson, J. S.; Hawkridge, A. M.; Muddiman, D. C. “Direct Characterization of Intact Polypeptides by Matrix-Assisted Laser Desorption Electrospray Ionization (MALDESI) Quadrupole Fourier Transfrom Ion Cyclotron Resonance Mass Spectrometry”Rapid Commun. Mass Spectrom. 2007, 21, 1150.
57. Nemes, J.; Vertes, A. “Laser Ablation Electrospray Ionization for Atmospheric Pressure, in Vivo, and Imaging Mass Spectrometry” Anal. Chem. 2007, 79, 8098.
58. Zubarev, R.A.; Kelleher, N.L.; McLafferty, F.W.”Electron Capture Dissociation of Multiply Charged Protein Cations - a Nonergodic Process” J. Am. Chem. Soc. 1998, 120, 3265.
59. Syka, J.E.P.; Coon J.J.; Schroeder, M.J.; Shabanowitz, J.; Hunt, D.F.
“Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry” PNAS. 2004, 101, 9528.
60. Hoffmann, E. D.; Charette, J.; Stroobant, V. “Mass Spectrometry -Principle and Applications” John Wiley & Sons: Chichester, New York, Brisbane, Toronto, Singapore, 1996.
61. Watson, J. T. “Introduction to Mass Spectrometry” 3rd ed.; Lippincott-Raven: Philadelphia, New York. 1997.
62. Gross, J. H. “Mass Spectrometry A Textbook” Spronger-Verlag:Berlin, Heidelberg, New York. 2004.
63. Dempster, A. J. “The Ionization and Dissociation of Hydrogen Molecules and the Formation of H3” Phil. Mag. 1916, 31, 438.
64. Cotter, R. “Plasma Desorption Mass Spect-rometry”Anal. Chem., 1988, 60, 781A.
65. Pachuta, S. J.;Cooks, R.G. “Mechanisms in Molecular SIMS. Anal. Rev. 1987, 87, 647.
66. Barber, M.; Bordoli, R. S.; Sedgwick, R. D.; Tyler, A. N. “Fast Atom Bombardment of Solids as An Ion Source in Mass Spectrometry” Nature. 1981, 293, 270 .
67. Barber, M.; Bordoli, R. S.; Elliott, G. J.; Sedgwick, R. D.; Tyler, A. N. ”Fast Atom Bombardment Mass Spectrometry” Anal. Chem. 1982, 54, 645A.
68. Posthumus, M. A.; Kistemker, P. G.; Meuzelaar H. L. C.; Brauw, M.C. “Laser Desorption Mass Spectrometry of Polar Nonvolatile Bio-Oranic Molecules”Anal.Chem. 1978, 50, 985.
69. Tabet, J. C.; Cotter, R. J. “Laser Desorption Time-of-Flight Mass Spectrometry of High Mass Molecules”Anal. Chem. 1984, 56, 1662.
70. Lin, S. Y.; Shih, S. H.; Wu, D.C.; Lee, Y. C.; Wu, C. I.; Lo, L. H.; Shiea, J. “Matrix-Assisted Laser Desorption Ionization/Time-of-Flight Mass Spectrometry for The Detection of Hemoglobins as the Protein Biomarkers for Fecal Occult Blood.” Rapid Commun Mass Spectrom. 2007, 21, 3311.
71. Wu, C. I.; Tsai, C. C.; Lu, C. C.; Wu, P. C.; Wu, D. C.; Lin, S. Y.; Shiea, J. “Diagnosis of Occult Blood in Human Feces Using Matrix-Assisted Laser Desorption Ionization/Time-of-Flight Mass Spectrometry.” Clin Chim Acta. 2007, 384, 86.
72. Pandey, A.; Mann, M. “Proteomics to study genes and genomes” Nature. 2000, 405, 837.
73. Yates, J. R. “ Proteomic Tools for Cell Biology”Traffic. 2000, 1, 747.
74. Peng, J.; Gygi, S. P. “Proteomics : the move to mixtures”J. Mass Spectrom. 2001, 36, 1083.
75. James, P. “Proteomics and automation” Electrophoresis. 1999, 20, 664.
76. Gevaert, K.; Vandekerckhove, J. “Protein identification methods in proteomics” Electrophoresis. 2000, 21, 1145.
77. Zenobi, R.; Knochenmuss, R. “Ion Formation in MALDI Mass Spectrometry”Mass Spectrometry Reviews. 1998, 17,337 .
78. Ehring, H.;Karas, M.; Hillenkamp, F. “Role of Photoionization and Photochemistry in Ionization Processes of Organic-Molecules and Relevance for Matrix-Assisted Laser Desorption Ionization Mass-Spectrometry”Org. Mass Spectrom. 1992, 27,472.
79. Weickhardt, C. Schmid, R. P. “Design reflectron time-of –flight mass spectrometers with and without grids: a direct comparison”International J. Mass Spectrom. 2001, 206, 181.
80. Spengler, B.; Kirsch, D.; Kaufmann, R. “Peptide Sequencing by Matrix-assisted Laser-desorption Mass Spectrometry”Rapid Commum. Mass Spectrom. 1992, 6, 105.
81. Ilani, T.; Ben-Shach, D.; Strous, R. D.; Mazor, M.; Sheinkman A.; Kotler, M.; Fuchs S. “A targeted mutation of the D3 dopamine receptor gene is associated with hyperactivity in mice “PNAS. 2001, 98, 625.
82. Mary, E. K.; Jeffrey, K. Y.; Daniel, P. V. K.” Plasma catecholamine metabolites as markers for psychosis and antipsychotic response in schizophrenia.”Neuropsychopharma. 1999 ,20,603.
83. Khawaja, X.; Xu, J.; Liang, J. J.; Barrett, J. E. ‘Proteomic Analysis of Protein Changes Developing in Rat Hippocampus After Chronic Antidepressant Treatment: Implications for Depressive Disorders and Future Therapies.” J. Neurosci. Res. 2004, 75, 451.
84. Tsai, S. J. “The possible role of tissue-type plasminogen activator and the plasminogen system in the pathogenesis of major depression. “Med. Hypotheses. 2006, 66, 319.
85. Tsai, S. J. “Statins may enhance the proteolytic cleavage of proBDNF: Implications for the treatment of depression.” Med. Hypotheses. 2007, 68, 1296.
86. Chen, C. C.; Huang, T. L. “Association of serum lipid profiles with depressive and anxiety disorders in menopausal women.” J. Chang. Gung. Med. 2006, 29, 325.
87. Huang, T. L. “Serum lipid profiles in major depression with clinical subtypes, suicide attempts and episodes.” J. Affect. Disord. 2005, 86, 75.
88. Huang, T. L.; Chen, J. F. “ Lipid and lipoprotein levels in depressive disorders with melancholic feature or atypical feature and dysthymia.” J. Psychiatry. Clin. Neurosci. 2004, 58, 295.
89. Huang, T. L.; Wu, S. C.; Chiang, Y. S.; Chen, J. F. “ Correlation between serum lipid, lipoprotein concentrations and anxious state, depressive state or major depressive disorder. “J. Psychiatry. Res. 2003, 118, 147.
90. Bruno, A.; Cumer, Bruno. S. “Effects of amitriptyline on the metabolism of catecholamines and serotonin in depressed patients.” J. Riv. Neurobiol. 1969, 15, 749.
91. Rosenblatt, S.; Chanley, J. D. “ The metabolism of norepinephrine in depressions. Differences and effects of therapies. “J. Can. Psychiatr. Assoc. 1966, Suppl, 50.
92. Petty, F.; Trivedi, M. H.; Fulton, M.; Rush, A. J.” Benzodiazepines as antidepressants: does GABA play a role in depression? “J. Biol. Psychiatry. 1995, 38, 578.
93. Kaiya, H.; Namba, M.; Yoshida, H.; Nakamura, S. “Plasma glutamate decarboxylase activity in neuropsychiatry. “ J. Psychiatry. Res. 1982, 6, 335.
94. Deuschle, M.; Blum, W. F.; Strasburger, C. J.; Schweiger, U.; Weber, B.; Körner, A.; Standhardt, H.; Gotthardt, U.; Schmider, J.; Pflaum, C. D.; Heuser, I.”Insulin-like growth factor-I (IGF-I) plasma concentrations are increased in depressed patients. “Psychoneuroendocrinology. 1997, 22, 493.
95. Maes, M.; Smith, R.; Christophe, A.; Vandoolaeghe, E.; Van, Gastel. A.; Neels, H.; Demedts, P.; Wauters, A.; Meltzer, H. Y.” Lower serum high-density lipoprotein cholesterol (HDL-C) in major depression and in depressed men with serious suicidal attempts: relationship with immune-inflammatory markers. “Acta. Psychiatr. Scand. 1997, 95, 212.
96. Sen, S.; Duman, R.; Sanacora, G.” Serum Brain-Derived Neurotrophic Factor, Depression, and Antidepressant Medications: Meta-Analyses and Implications .” Biol Psychiatry. 2008, 64, 527.
97. Huang, T. L.; Lee, C. T.; Liu, Y. L.’ Serum brain-derived neurotrophic factor levels in patients with major depression: Effects of antidepressants.” J Psychiatr Res. 2008, 42, 521.
98. Yang, Y.; Wan, C.; Li, H.; Zhu, H.; La, Y.; Xi, Z.; Chen, Y.; Jiang, L. ; Feng, G.; He, L.” Dysregulation of Retinoid Transporters Expression in Body Fluids of Schizophrenia Patients.” Anal. Chem. 2006, 78, 3571.
99. Hsieh, Y. Casale, R. Fukuda E. “Matrix-Assisted Laser Desorption /Ionization Imaging Mass Spectrometry for Direct Measurement of Clozapine in Rat Brain Tissue”Rapid Common. Mass Spectrom. 2006, 20, 965.
100. Hsieh, Y.; Chen, J.; Korfmacher, W. A. “Mapping Pharmaceuticals in Tissue Using MALDI Imaging Mass Spectrometry”J. Pharm. Toxic. Methods. 2007, 55, 193.
101. Shahidi, K.S.; Andersson, M.;Herman J.L.; Gillespie, T.A.; Caprioli R.M. “Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry.”Anal. Chem. 2006, 78,6448.
102. O’Farrell, P. H. “High Resolution Two-Dimensional Electrophoresis of Proteins.”J. Biol. Chem. 1975, 250, 4007.
103. Klose, J. “Protein mapping by combined isoelectric focusing and electrophoresis of mouse tissues. A novel approach to testing for induced point mutations in mammals.” Humangenetik. 1975, 26, 231.
104. Anderson, N. L.; Anderson, N. G. ‘High resolution two-dimensional electrophoresis of human plasma proteins.” Proc. Natl. Acad. Sci. USA. 1977, 74, 5421.
105. Yates, J. R. III. “Mass spectrometry and the age of the proteome. “J. Mass Spectrom. 1998, 33, 1-19.
106. Aebersold, R.; Patterson, S. D. “Mass spectrometric approaches for the identification of gel-separated proteins.” Electrophoresis. 1995, 16, 1791.
107. Mann, M.; Hendrickson, R. C.; Pandey, A. “Analysis of proteins and proteomes by mass spectrometry.” Annu. Rev. Biochem.2001, 70, 437.
108. Swatton, J. E.; Prabakaran, S.; Karp, N. A.; Lilley, K.S. Bahn, S.” Protein profiling of human post-mortem brain using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE).”Mol Psychiatry. 2004 , 9,128.
109. http://www.immunecliniclondon.com
110. Fisrt, M.B.; Spitzer, R.L.; Gibbon, M.; Williams, J.B.W. User’s Guide for the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV). Washington, DC, American Psychiatric Press. 1997.
111. 李明濱. “精神醫學新知” 台灣醫學會出版. 1999.
112. http://www.bali.doh.gov.tw/bulletin.do?opr=info
113. http://www.rpi.edu/~bellos/new_page_2.htm
114. en.wikipedia.org/wiki?title=Serotonin
115. http://www.bymaster.org/frank/pix/MonoamineHypothesis.JPG
116. Mary, F. L.; Alvydas, M.;Scott, K.; David, A. B.; Jeremiah, K.; Eva, G.; Joseph, D.; Eric, D.; Wayne, F. P.; Richard, E.; Lisa, S.; Tillmann, Z.; Christopher, L.; Susan, K.; Gordon, R. W.; Michael, R. ; Wall, D. P. ; Mannion, G.; Cioppa, S. ; Gershon, M. W.” High-Resolution Serum Proteomic Profiling of Alzheimer Disease Samples Reveals Disease-Specific, Carrier-Protein–Bound Mass Signatures” Clinic. Chem. 2005,51, 1946 .
117. Li, A.; Sowder, R. C.; Henderson, L. E.; Moore, S. P.; Garfinkel, D. J.; Fisher, R. J. “Chemical cleavage at aspartyl residues for protein identification.” Anal. Chem. 2001, 73, 5395.
118. Yao, Z. P.; Afonso, C.; Fenselau, C. “Rapid microorganism identification with on-slide proteolytic digestion followed by matrix-assisted laser desorption/ionization tandem mass spectrometry and database searching.” Rapid Commun. Mass Spectrom. 2002, 16, 1953.
119. Zhong, H.; Marcus, S. L.; Li, L. “Microwave-assisted acid hydrolysis. of proteins combined with liquid chromatography MALDI MS/MS for Protein Identification” J. Am. Soc. Mass Spectrom. 2005, 16, 471.
120. Zhong, H.;Zhang, Y.; Wen, Z,; Li, L.” Protein sequencing by mass analysis of polypeptide ladders after controlled protein hydrolysis. “Nat. Biotechnol. 2004, 22, 1291.
121. Swatkoski, S.; Russell, S.C.; Edwards, N.; Fenselau, C. “Rapid Chemical Digestion of Small Acid-Soluble Spore Proteins for Analysis of Bacillus Spores. “Anal. Chem. 2006, 78, 181.
122. Warscheid, B.; Fenselau, C. “Characterization of Bacillus Spore Species and Their Mixtures Using Postsource Decay with a Curved-Field Reflectron. “Anal. Chem. 2003, 75, 5618.
123. Warscheid, B.; Jackson, K.; Sutton, C.; Fenselau, C. “MALDI Analysis of Bacilli in Spore Mixtures by Applying a Quadrupole Ion Trap Time-of-Flight Tandem Mass Spectrometer.” Anal. Chem. 2003, 75, 5608.
124. http://www.research-innovation.ed.ac.uk
125. http://transferrinstl.blogspot.com
126. http://www.bmsc.washington.edu/people/teller/suppl.html
127. Fuss, C.; Palmaz, J.C.; Sprague, E.A.” Fibrinogen: structure, function, and surface interactions. “ J. Vasc. Interv. Radiol. 2001; 12, 677.
128. Watt, K.W.; Takagi, T.; Doolittle, R.F.” Amino acid sequence of the beta chain of human fibrinogen: homology with the gamma chain. “Proc Natl Acad Sci U S A 1978, 75, 1731.
129. Pandey, G. N.; Dwivedi, Y. “Focus on Protein kinase A and protein kinase C, Critical components of signal transduction system, in mood disorders and suicide.” Int J Neuropsychopharmacol. 2005, 8,1.
130. Maes, M.; Delange, J.; Ranjan, R.; Meltzer, H. Y.; Cooremans, D. W.; Scharpe, S. “Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs.” Psychiatry Res. 1997, 66,1.
131. Hornig, M.; Goodman, D. B. P.; Kamoun, M.; Amsterdam, J. D. “Positive and negative acute phase proteins in affective subtypes.” J Affect Disord. 1998, 49, 9.
132. Wong, C. T.; Tsoi, W. F.; Saha, N. “Acute phase proteins in male Chinese schizophrenic patients in Singapore.” Schizophr Res. 1996, 22, 165.
133. Jiang, L.; Lindpaintner, K.; Li, H. F.; Gu, N. F.; Langen, H.; He, L. Fountoulakis, M. “Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia.” Amino Acids. 2003, 25, 49.
134. 134、 Pfeffer, A.; Rogers, K. M. Acute phase response of sheep: changes in the concentrations of ceruloplasmin, fibrinogen, haptoglobin and the major blood cell types associated with pulmonary damage. Res Vet Sci. 1989, 46, 118.
135. Smith, R.”The macrophage theory of depression. “Med. Hypoth. 1991, 35,298.
136. Vaccarino, V.; Brennan, M. L.; Miller, A. H.; Bremner, J. D.; Ritchie, J. C.; Lindau, F.; Veledar, E.; Su, S.; Murrah, N. V.; Jones, L.; Jawed, F.; Dai, J.; Goldberg, J.; Hazen, S. L. “Association of Major Depressive Disorder with Serum Myeloperoxidase and Other Markers of Inflammation: A Twin Study. “Biol Psychiatry. 2008, 64,476.
137. Bremmer, M. A.; Beekman, A. T.; Deeg, D. J.; Penninx, B. W.; Dik, M. G.; Hack, C. E.; Hoogendijk, W. J.” Inflammatory markers in late-life depression: results from a population-based study. “J Affect Disord. 2008, 106, 249.
138. Rothermundt, M.; Arolt, V.; Peters, M.; Gutbrodt, H.; Fenker, J.; Kersting, A.; Kirchner, H. “Inflammatory markers in major depression and melancholia. “J Affect Disord. 2001, 63,93.
139. Berk, M.; Wadee, A. A.; Kuschke, R. H.; O’Neill-Kerr, A.” Acute phase proteins in major depression. “J. Psychosom. Res. 1997, 43, 529.
140. Seidel, A.; Arolt, V.; Hunstiger, M.; Rink, L.; Behnisch, A.; Kirchner, H.” Cytokine production and serum proteins in depression.” J. Immunol. 1995, 41, 534.
141. Joyce, P. R. H. C. R.; Mulder, R. T.; Sellman, J. D.; Wilson, D. A.; Boswell, D. R. “Elevated levels of acute phase plasma proteins in major depression.” Biol. Psychiatry. 1992, 32, 1035.
142. Sitek, B.; Apostolov, O.; Stuhler, K.; Pfeiffer, K.; Meyer, H.; Eggert, A.; Schramm, A. “Identification of Dynamic Proteome Changes Upon Ligand Activation of Trk-Receptors Using Two-dimensional Fluorescence Difference Gel Electrophoresis and Mass Spectrometry.” Mol Cell Proteomics. 2005, 4, 291.
143. Adams, J.H.P.; Brott, T.G. ; Crowell, R. M. ; Furlana, J.; Gomez, C. R. ; Grotta, J.; Helgason, M. J. R.;Woolson, R. F. ; Zivin, J.A.; Feinberg, W.; Mayberg, M. “Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association.” Stroke. 1994,25,1901.
144. Hoc, A. “European strategies for early intervention in stroke. A report of an Ad Hoc Consensus Group Meeting.” Cerebrovasc Dis. 1996, 6, 315.
145. Allard, L.; Lescuyer, P.; Burgess, J.; Leung ,K.Y.; Ward, M.; Walter, N. Sanchez, J.C. “ApoC-I and ApoC-III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke.” Proteomics. 2005, 4, 2242.
146. Zimmermann-Ivol, C.G.; Burkhard, P.R.; Allard, L.; Hochstrasser , D.F.; Sanchez, J.C.” Fatty acid binding protein as a serum marker for the early diagnosis of stroke: a pilot study. “Mol Cell Proteomics. 2004, 3, 66.
147. Anand, N.; Stead, L.G.” Neuron-specific enolase as a marker for acute ischemic stroke: a systematic review.” Cerebrovasc Dis.2005, 20, 213.
148. Wunderlich, M.T.; Hanhoff, T.; Goertler, M.; Spener, F.; Glatz, J.F.; Wallesch, C.W.; Pelsers, M.M. „ Release of brain-type and heart-type fatty acid-binding proteins in serum after acute ischaemic stroke. “J Neurol. 2005, 252,718.
149. Baird, A.E. “Blood biologic markers of stroke: improved management, reduced cost? “Curr Atheroscler Rep. 2006, 8, 267.
150. Lescuyer, P.;Allard, L.; Zimmermann-Ivol, C.G.; Burgess, J.A.; Hughes-Frutiger, S.; Burkhard, P.R.; Sanchez, J.C. Hochstrasser, D.F.” Identification of post-mortem cerebrospinal fluid proteins as potential biomarkers of ischemia and neurodegeneration. “Proteomics. 2004, 4, 2234.
151. Lam, N.Y. ;Rainer, T.H.; Wong, L.K.; Lam, W. ;Lo, Y.M. “ Plasma DNA as a prognostic marker for stroke patients with negative neuroimaging within the first 24 h of symptom onset. “Resuscitation. 2006, 68, 71.
152. Castellanos, M.; Serena, J.” Applicability of biomarkers in ischemic stroke.” Cerebrovasc Dis. 2007, 24, 7.
153. Reynolds, M.A.; Kirchick, H.J.; Dahlen, J.R.; Anderberg, J.M.; McPherson, P.H.; Nakamura, K.K.; Laskowitz, D.T.; Valkirs, G.E.; Buechler, K.F.” Early biomarkers of stroke.” Clin Chem. 2003, 49, 1733.
154. Lezcano, N.E.; Odo, N.;Kutlar, A.; Brambilla, D.; Adams, R.J.” Regular transfusion lowers plasma free hemoglobin in children with sickle-cell disease at risk for stroke. “Stroke. 2006, 37, 1424.
155. Buttari, B.; Profumo, E.; Petrone, L.; Pietraforte, D.; Siracusano, A.; Margutti, P.; Delunardo, F.; Ortona, E.; Minetti, M.; Salvati, B.; Riganò, R.”Free hemoglobin: a dangerous signal for the immune system in patients with carotid atherosclerosis? “Ann NY Acad Sci. 2007, 1107, 42.
156. Rother, R.P.; Bell, L.; Hillmen, P.; Gladwin, M.T.” The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. “JAMA. 2005, 293, 1653.
157. Na, N.; Ouyang, J.; Taes, Y.E.; Delanghe, J.R.”Serum free hemoglobin concentrations in healthy individuals are related to haptoglobin type.” Clin Chem. 2005, 51, 1754.
158. Joseph, G.; Tarnow, L.; Astrup, A.S.; Hanse, T.K.; Parving, H.; Flyvbjerg, A.; Frystyk, J. “Plasma α-defensin is associated with cardiovascular morbidity and mortality in type 1 diabetic patients.” J. Clin. Endocrin Metab. 2008, 93, 1470.
159. Craddock, R.M.; Huang, J.T.; Jackson, E.; Harris, N.; Torrey, E.F.; Herberth, M.; Bahn, S. “Increased Alpha Defensins as a Blood Marker for Schizophrenia Susceptibility.” Mol. Cell Proteomics, 2008, 7, 1204.
160. Ganz, T. “Defensins:Antimicrobial Peptides of innate immunity.” Nature, 2003, 3, 710.
161. Tollin, M.; Bergman, P.; Svenberg, T.; Jörnvall, H.; Gudmundsson, G.H.; Agerberth, B. ”Antimicrobial peptides in the first line defence of human colon mucosa” Peptides. 2003, 24, 523
162. Holterman, D.A.; Diaz, J.I.; Blackmore, P.F.; Davis, J.W.; Schelhammer, P.F.; Corica, A.; Semmes, O.J.; Vlahou, A. “Overexpression ofα-defensin us associated with bladder cancer invasiveness.” Urologic Oncology: Seminars and Orginal Investigations. 2006, 24, 97.
163. Tao, R.; Jurevic, R.j.; Coulton, K.K.; Tsutsui, M.T.; Roberts, M.C.; Kimball, J.R.; Wells, N.; Berndt, J.; Dale, B.A. “Salivary Antimicrobial Peptide Expression and Dental Caries Experience in Children.” Antimicrob. Agents Chemother. 2005, 49, 3883.
164. Mizukawa, N.; Sugiyama, K.; Ueno, T.; Mishima, K.; Takagi, S.; Sugahara, T. “Levels of human defensin-1, an antimicrobial peptide, in saliva of patients with oral inflammation.” Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999. 87, 539.
165. Munro, N.P.; Cairns D.A.; Clarke, P.; Rogers, M.; Stanley, A.J.; Barrett, J.H.; Harnden, P.; Thompson, D.; Eardley, I.; Banks, R.E.; Knowles, M.A. “Urinary biomarker profiling in transitional cell carcinoma.” Int. J. Cancer. 2006, 119, 2642.
166. Vlahou, A.; Schellhammer, P.F.; Mendrinos, S.; Patel, K.; Kondylis, F.I.; Gong, L.; Nasim, S.; Wright, G.L. “Development of a Novel Proteomic Approach for the Detection of Transitional Cell Carcinoma of the Bladder in Urine.” American Journal of Patbology. 2001, 158, 1491.
167. Anne, E. K.; Hilary, O.D.C.; Rodney, W. K.” Innate immune defences in the human endometrium” Reproduct. Biol. Endocrinol. 2003, 1,116.
168. Mary, E. K. ; Theresa, L. C. “Defensins in innate antiviral immunity” Nat.Rev. Immunol. 2006, 6, 447.
169. http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/ Eyef04/Eye.f04.html
170. Stevie, F. A.; Wilson, R. G.; Simons, D. S.; Current, M. I.; Zalm, P. C.“Review of Secondary Ion Mass Spectrometry Characterization of Contamination Associated with Ion Implantion ”J. Vac. Scl. Technol. B. 1994, 12, 2263.
171. McMahon, J. M.; Short, R. T.; McCandish, C. A.; Brenna, J. T.; Todd, P. J. “Identification and Mapping of Phosphocholine in Animal Tissue by Static Secondary Ion Mass Spectrometry and Tandem Mass Spectrometry”Rapid Commun. Mass Spectrom. 1996, 10, 335.
172. McCandish, C. A.; McMahon, J. M.; Todd, P. J. “Secondary Ion Images of the Rodent Brain”J. Am. Soc. Mass Spectrom. 2000, 11, 191.
173. Daolio, S.; Fabrizio, M.; Piccirillo, C. “Secondary Ion Mass Spectrometry in the Characterisation of Boron-based Ceramics” Rappid Commun. Mass Spectrom. 2001, 15, 1.
174. Todd, P. J.; Schaaff, T. G.; Chaurand, P.; Caprioli, R. M. “Organic Ion Imaging of Biological Tissue with Secondary Ion Mass Spectrometry and Matrix-Assisted Laser Desorption / Ionization”J. Mass Spectrom. 2001, 36, 355.
175. Todd, P. J.; McMahon, J. M.; McCandish, C. A. “Secondary Ion Images of the Developing Rat Brain”J. Am. Soc. Mass Spectrom. 2004, 15, 1116.
176. Ostrowski, S. G.; Bell, C. T. V.; Winograd, N.; Ewing, A. G. “Mass Spectrometric Imaging of Highly Curved Membranes During Tetrahymena Mating” Science. 2004, 305, 71.
177. McPhail, D. S. “Applications of Secondary Ion MassSpectrometry (SIMS) in Materials Science”J. Mater. Sci. 2006, 41, 873 178.
178. Chaurand, P.; Schwartz, S. A.; Caprioli, R. M. “Profiling and Imaging Proteins in Tissue Sections by MS”Anal. Chem. 2004, 1, 86A.
179. Caprioli, R. M.; Farmer, T. B.; Gile, J. “Molecular Imaging of Biological Samples: Localization of Peptides and Proteins Using MALDI-TOF MS”Anal. Chem. 1997, 69, 4751.
180. Lee, C.; Nansie, A.; McHugh, Y.; Chen.J.” Investigation of the profiling depth in matrix-assisted laser desorption/ionization imaging mass spectrometry”Rapid Commun. Mass Spectrom. 2006, 20, 284.
181. Todd, P.J.; Schaaff, T.G.; Chaurand, P.; Caprioli, R.M.” Organic ion imaging of biological tissue with secondary ion mass spectrometry and matrix-assisted laser desorption/ionization” J. Mass Spectrom. 2001, 36, 355.
182. Caprioli, R.M.; Farmer, T.B.; Gile, J.” Molecular Imaging of Biological Samples: Localization of Peptides and Proteins Using MALDI-TOF MS” Anal. Chem. 1997, 69, 4751.
183. Virginia, E.; Julia, D.; Wulfkuhle, V. S.; Calvert, A. ;Lance, A. L.” Laser-capture microdissection”Nature Protocols. 2006, 1, 586.
184. www.cgmh.org.tw/intr/intr4/c8910/FROZEN.HTM
185. Sarah, A.; Schwartz, M. L.; Caprioli, M. “Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation”J. Mass Spectrom. 2003, 38, 699.
186. Stoeckli, M.; Chaurand, P.; Hallahan, D.E.; Caprioli, R.M. “Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues.” Nat. Med. 2001. 7, 493.
187. Stoeckli, M.;Staab, D.; Staufenbiel, M.; Wiederhold, K.H,; Signor,L.;”Molecular imaging of amyloid beta peptides in mouse brain sections using mass spectrometry.” Anal. Biochem. 2002, 311, 33.
188. Baluya, D.L.; Garrett, T.J.; Yost, R.A. “Automated MALDI Matrix Deposition Method with Inkjet Printing for Imaging Mass Spectrometry”Anal. Chem., 2006, 79, 6862 .
189. Aerni, H.R.; Cornett, D.S.; Caprioli, R.M.” Automated acoustic matrix deposition for MALDI sample preparation.” Anal Chem. 2006 ,78,827.
190. Lemaire, J. C. ;Tabet, P. D.; Hendra, J. B. ; Salzet, M. ; Fournier, I. “Solid ionic matrixes for direct tissue analysis and MALDI imaging.”Anal. Chem. 2006, 78 , 809.
191. Taira, S.; Sugiura, Y.; Moritake, S.; Shimma, S.; Ichiyanagi, Y.; Setou, M. “Nanoparticle-Assisted Laser Desorption/Ionization Based Mass Imaging with Cellular Resolution “Anal. Chem. 2008, 80, 4761.
192. Spengler, B.; Hubert, M.” Improvement of Biological Time-of-Flight-Secondary Ion Mass Spectrometry Imaging with a Bismuth Cluster Ion Source “ J Am Soc Mass Spectrom. 2002, 13, 735.
193. Martin, K.; Dieter, K.; Alfons, H.; Arne, L.; Sabine, G.;Bernhard, S.“A high-resolution scanning microprobe matrix-assisted laser desorption/ionization ion source for imaging analysis on an ion trap/Fourier transform ion cyclotron resonance mass spectrometer”Rapid Commun. Mass Spectrom. 2008, 22, 3275.
194. Pierre, C.;Beverly, B.; DaGue1, R.; Scott, P.; David, W.; Caprioli, R. M. “Profiling proteins from azoxymethane-induced colon tumors at the molecular level by matrix-assisted laser desorption/ionization mass spectrometry”Proteomics. 2001, 1, 1320.
195. Tatiana, C.; Rohner, D.; Staab, M.” MALDI mass spectrometric imaging of biological tissue sections” Mechan. Age. Devel.2005, 126 , 177.
196. Groseclose, M.R.; Andersson, M.; Hardesty, W.M.; Caprioli R.M. “Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry”J. Mass Spectrom. 2007; 42: 254–262
197. Cornett, D.S.; Frappier, S.L.; Caprioli, R.M. “MALDI-FTICR Imaging Mass Spectrometry of Drugs and Metabolites in Tissue “Anal. Chem. 2008, 80, 5648.
198. McDonnell, L.A.; Piersma, S.R.; Maarten, A. A. F.; Mize, T.H.; Luxembourg, S.L.; Verhaert, P.D.; Heeren, R. M.” Subcellular imaging mass spectrometry of brain tissue.” J Mass Spectrom. 2005,40,160.
199. Wiseman, J.M.; Ifa, D.R.; Song, Q.; Cooks, R.G. “Tissue Imaging at Atmospheric Pressure Using Desorption Electrospray Ionization (DESI) Mass Spectrometry”Angew. Chem. Int. Ed. 2006, 45, 7188 .
200. Wiseman, J.M.; Ifa, D.R.; Zhu, Y.; Kissinger, C.B.; Manicke, N.E.; Kissinger, P.T.; Cooks, R.G. “Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues“Proc. Nat. Acad. Sci. U.S.A. 2008, 105, 18120.
201. Kertesz, V.; B, G.J.; Vavrek, M.; Koeplinger, K.A.; Schneider, B.B.; Covey, T.R. “Comparison of Drug Distribution Images from Whole-Body Thin Tissue Sections Obtained Using Desorption Electrospray Ionization Tandem Mass Spectrometry and Autoradiography”Anal. Chem. 2008, 80, 5168.
202. Lemaire, R.; Desmons, A.; Tabet, J.C.; Day, R.; Salzet, M.” Direct analysis and MALDI imaging of formalin-fixed, paraffin-embedded tissue sections.”J Proteome Res. 2007, 6,1295.
203. Stauber, J.; Lemaire, R.; Franck, J.; Bonnel, D.; Croix, D.; Day, R.; Wisztorski, M.; Fournier, I.; Salzet, M.” MALDI imaging of formalin-fixed paraffin-embedded tissues: application to model animals of Parkinson disease for biomarker hunting.”J Proteome Res. 2008, 7,969.
204. Li, Y.; Shrestha, B. Vertes, A.” Atmospheric pressure infrared MALDI imaging mass spectrometry for plant metabolites.”Anal. Chem. 2008, 80, 407.
205. Li, Y.; Shrestha, B. Vertes, A. “Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry”Anal Chem. 2007, 79, 523.
206. Octavio, G. A.; Elizabeth, L. A.;Teresa, O. “Expression of the Newcastle disease virus fusion protein in transgenic maize and immunological studies” Transgenic Res. 2006, 15, 455.
207. http://www.fao.org/DOCREP/005/AC802E/ac802e0o.htm
208. http://www.brandeis.edu/projects/wanghlab/
209. Brown, B. E. “Coral bleaching: causes and consequences. “Coral Reefs. 1997, 16, 129.
210. Malakoff, D. “Extinction on the high seas.”Science. 1997, 277, 487.
211. Hoegh-Guldberg, O. “Climate change,coral bleaching and the future of the world’s coral reefs.” Mar. Freshwater Res.1999, 50, 839.
212. Wilkinson, C. R. “Global and local threats to coral reef functioning and existence: review and predictions.” Mar. Freshwater Freshwater Res. 1999, 50, 867.
213. Burke, L.; Selig, E.; Spalding, M.” Reefs at risk in southeast Asia. “World Resource Institute, Washington D.C., USA, 72.
214. Gleason, D. F.; Wellington, G. M. “Ultraviolet radiation and coral bleaching.” Nature. 1993, 365, 836.
215. http://www.nmmba.gov.tw
216. http://baike.baidu.com/view/597335.htm