Richard M. Caprioli, Ph.D.


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Faculty Appointments
Director, Mass Spectrometry Center Professor of Biochemistry Professor of ChemistryStanford Moore Chair in BiochemistryProfessor of MedicineProfessor of Pharmacology
Ph.D., Biochemistry, Columbia University, New York, New YorkB.S., Pharmacy, Columbia University, New York, New York
Office Address
9160 MRB III
465 21st Avenue S.
Nashville, TN 37232-8575
Research Description
The research interests of this laboratory are aimed at the investigation of biological processes involving the synthesis, modification, storage and degradation of certain peptides and proteins using modern mass spectrometric methods of analysis to follow molecular events. In recent years there has been a great amount of interest in investigating the biochemical events involved in the metabolism of peptides, primarily in the brain and gut of mammals, encompassing the enzymatic breakdown of these peptides, their production from peptide and protein precursors, and the disruption of these processes by certain xenobiotics. Modern mass spectrometric techniques are used in these studies, including electrospray and matrix-assisted laser desorption ionization mass spectrometry. This research is generally carried out with two experimental approaches.

The first involves in vivo metabolic studies in live animals (rats) using microdialysis sampling procedures together with molecular identification and quantitation by electrospray tandem mass spectrometry. This experimental approach allows us to measure metabolic events that occur in freely moving animals at a level of 50-100 attomoles in the tissue dialysate. Integrated technology for microdialysis/mass spectrometry utilizes quadrupole mass spectrometry (MS/MS) and micro-electrospray ionization (micro-ESI) for very high sensitivity measurements. The micro-ESI source has been optimized to produce ions from the electrospray process at sub-microliter per min flow rates. The application of combined microdialysis/ESI mass spectrometry is ongoing in four areas, i) Investigation of the kinetics and quantitative aspects of the in vivo metabolism of the neuropeptides and enkephalin neuropeptides, ii) Studies of the kinetics and differential processing of opioid peptide fragment precursors in vivo, iii) Investigation of the in vivo quantitative production and enzymatic degradation of N-acetylaspartyl-glutamate in seizure disorders using a rat model, and iv) Development and measurements of in vivo drug pharmacokinetics, using the drugs haloperidol, valproic acid, cocaine, amphetamine, and the new GABA antagonist n-butyl-3 aminopropylphosphinic acid.

The second experimental approach used in the study of cellular peptide metabolism utilizes new molecular imaging technology that is being developed in our lab. This method involves molecular mapping of animal tissue through the production of ion images obtained from the analysis of mammalian tissue slices by matrix-assisted laser desorption mass spectrometry (MALDI MS)12. This technique permits a tissue section to be mapped in multiple molecular weight values, localizing the molecules in an X, Y coordinate representation of the sample. Ion images are produced by repetitive exposure of the sample to the laser beam, where adjacent spots are irradiated, resulting in an ordered array of mass spectra that are keyed to specific locations in the sample. From one raster of the sample, a specific ion image, at any chosen m/z value, could be produced to give the spatial arrangement of molecules of interest. Current work involves; i) Instrument development involving modifications to an existing commercial MALDI (TOF) mass spectrometer, including changes to the laser optics, target movement system, and instrument control hardware and software, ii) Development of methods for sample preparation and target surface modifications to achieve high sensitivity and high image resolution, with molecular specificity, and iii) Applications to specific research areas involving questions about certain spatial distributions of molecules within specific tissues.
Research Keywords
Metabolism of cellular peptides
Mathur BN, Caprioli RM, Deutch AY. Proteomic analysis illuminates a novel structural definition of the claustrum and insula. Cereb. Cortex [print-electronic]. 2009 Oct; 19(10): 2372-9. PMID: 19168664, PMCID: PMC2742595, PII: bhn253, DOI: 10.1093/cercor/bhn253, ISSN: 1460-2199.

Aerni HR, Cornett DS, Caprioli RM. High-throughput profiling of formalin-fixed paraffin-embedded tissue using parallel electrophoresis and matrix-assisted laser desorption ionization mass spectrometry. Anal. Chem. 2009 Sep 9/1/2009; 81(17): 7490-5. PMID: 19650658, PMCID: PMC2747050, DOI: 10.1021/ac900974j, ISSN: 1520-6882.

Grey AC, Chaurand P, Caprioli RM, Schey KL. MALDI imaging mass spectrometry of integral membrane proteins from ocular lens and retinal tissue. J. Proteome Res. 2009 Jul; 8(7): 3278-83. PMID: 19326924, PMCID: PMC2715141, DOI: 10.1021/pr800956y, ISSN: 1535-3893.

Konkle ME, Hargrove TY, Kleshchenko YY, von Kries JP, Ridenour W, Uddin MJ, Caprioli RM, Marnett LJ, Nes WD, Villalta F, Waterman MR, Lepesheva GI. Indomethacin amides as a novel molecular scaffold for targeting Trypanosoma cruzi sterol 14alpha-demethylase. J. Med. Chem. 2009 May 5/14/2009; 52(9): 2846-53. PMID: 19354253, PMCID: PMC2744100, DOI: 10.1021/jm801643b, ISSN: 1520-4804.

Xu BJ, Li J, Beauchamp RD, Shyr Y, Li M, Washington MK, Yeatman TJ, Whitehead RH, Coffey RJ, Caprioli RM. Identification of early intestinal neoplasia protein biomarkers using laser capture microdissection and MALDI MS. Mol. Cell Proteomics [print-electronic]. 2009 May; 8(5): 936-45. PMID: 19164278, PMCID: PMC2689774, PII: M800345-MCP200, DOI: 10.1074/mcp.M800345-MCP200, ISSN: 1535-9484.

Seeley EH, Caprioli RM. Molecular imaging of proteins in tissues by mass spectrometry. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2008 Nov 11/25/2008; 105(47): 18126-31. PMID: 18776051, PMCID: PMC2587620, PII: 0801374105, DOI: 10.1073/pnas.0801374105, ISSN: 1091-6490.

Lee YT, Dimitrova YN, Schneider G, Ridenour WB, Bhattacharya S, Soss SE, Caprioli RM, Filipek A, Chazin WJ. Structure of the S100A6 complex with a fragment from the C-terminal domain of Siah-1 interacting protein: a novel mode for S100 protein target recognition. Biochemistry [print-electronic]. 2008 Oct 10/14/2008; 47(41): 10921-32. PMID: 18803400, PMCID: PMC2666074, DOI: 10.1021/bi801233z, ISSN: 1520-4995.

Groseclose MR, Massion PP, Chaurand P, Caprioli RM. High-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue microarrays using MALDI imaging mass spectrometry. Proteomics. 2008 Sep; 8(18): 3715-24. PMID: 18712763, PMCID: PMC2927989, DOI: 10.1002/pmic.200800495, ISSN: 1615-9861.

Chaurand P, Latham JC, Lane KB, Mobley JA, Polosukhin VV, Wirth PS, Nanney LB, Caprioli RM. Imaging mass spectrometry of intact proteins from alcohol-preserved tissue specimens: bypassing formalin fixation. J. Proteome Res [print-electronic]. 2008 Aug; 7(8): 3543-55. PMID: 18613713, PMCID: PMC2927987, DOI: 10.1021/pr800286z, ISSN: 1535-3893.

Seeley EH, Oppenheimer SR, Mi D, Chaurand P, Caprioli RM. Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections. J. Am. Soc. Mass Spectrom [print-electronic]. 2008 Aug; 19(8): 1069-77. PMID: 18472274, PMCID: PMC2582528, PII: S1044-0305(08)00227-4, DOI: 10.1016/j.jasms.2008.03.016, ISSN: 1044-0305.

Cornett DS, Frappier SL, Caprioli RM. MALDI-FTICR imaging mass spectrometry of drugs and metabolites in tissue. Anal. Chem [print-electronic]. 2008 Jul 7/15/2008; 80(14): 5648-53. PMID: 18564854, PMCID: PMC2924168, DOI: 10.1021/ac800617s, ISSN: 1520-6882.

Burnum KE, Tranguch S, Mi D, Daikoku T, Dey SK, Caprioli RM. Imaging mass spectrometry reveals unique protein profiles during embryo implantation. Endocrinology [print-electronic]. 2008 Jul; 149(7): 3274-8. PMID: 18403475, PMCID: PMC2453082, PII: en.2008-0309, DOI: 10.1210/en.2008-0309, ISSN: 0013-7227.

Puolitaival SM, Burnum KE, Cornett DS, Caprioli RM. Solvent-free matrix dry-coating for MALDI imaging of phospholipids. J. Am. Soc. Mass Spectrom [print-electronic]. 2008 Jun; 19(6): 882-6. PMID: 18378160, PMCID: PMC2696184, PII: S1044-0305(08)00119-0, DOI: 10.1016/j.jasms.2008.02.013, ISSN: 1044-0305.

Hardesty WM, Caprioli RM. In situ molecular imaging of proteins in tissues using mass spectrometry. Anal Bioanal Chem. 2008 Jun; 391(3): 899-903. PMID: 18365184, PMCID: PMC2921695, DOI: 10.1007/s00216-008-1972-5, ISSN: 1618-2650.

Manier ML, Cornett DS, Hachey DL, Caprioli RM. Identification of dimethyldioctadecylammonium ion (m/z 550.6) and related species (m/z 522.6, 494.6) as a source of contamination in mass spectrometry. J. Am. Soc. Mass Spectrom [print-electronic]. 2008 May; 19(5): 666-70. PMID: 18328728, PMCID: PMC2516304, PII: S1044-0305(08)00118-9, DOI: 10.1016/j.jasms.2008.01.015, ISSN: 1044-0305.

Caldwell RL, Opalenik SR, Davidson JM, Caprioli RM, Nanney LB. Tissue profiling MALDI mass spectrometry reveals prominent calcium-binding proteins in the proteome of regenerative MRL mouse wounds. Wound Repair Regen [print-electronic]. 2008 May; 16(3): 442-9. PMID: 18282264, PMCID: PMC2891803, PII: WRR351, DOI: 10.1111/j.1524-475X.2007.00351.x, ISSN: 1524-475X.

Sanders ME, Dias EC, Xu BJ, Mobley JA, Billheimer D, Roder H, Grigorieva J, Dowsett M, Arteaga CL, Caprioli RM. Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. J. Proteome Res [print-electronic]. 2008 Apr; 7(4): 1500-7. PMID: 18386930, PMCID: PMC2738605, DOI: 10.1021/pr7008109, ISSN: 1535-3893.

Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science. 2008 Feb 2/15/2008; 319(5865): 962-5. PMID: 18276893, PII: 319/5865/962, DOI: 10.1126/science.1152449, ISSN: 1095-9203.

Chaurand P, Rahman MA, Hunt T, Mobley JA, Gu G, Latham JC, Caprioli RM, Kasper S. Monitoring mouse prostate development by profiling and imaging mass spectrometry. Mol. Cell Proteomics [print-electronic]. 2008 Feb; 7(2): 411-23. PMID: 17991918, PII: M700190-MCP200, DOI: 10.1074/mcp.M700190-MCP200, ISSN: 1535-9484.

Andersson M, Groseclose MR, Deutch AY, Caprioli RM. Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction. Nat. Methods. 2008 Jan; 5(1): 101-8. PMID: 18165806, PII: nmeth1145, DOI: 10.1038/nmeth1145, ISSN: 1548-7105.

Sinha TK, Khatib-Shahidi S, Yankeelov TE, Mapara K, Ehtesham M, Cornett DS, Dawant BM, Caprioli RM, Gore JC. Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging. Nat. Methods [print-electronic]. 2008 Jan; 5(1): 57-9. PMID: 18084298, PMCID: PMC2649801, PII: nmeth1147, DOI: 10.1038/nmeth1147, ISSN: 1548-7105.

Herring KD, Oppenheimer SR, Caprioli RM. Direct tissue analysis by matrix-assisted laser desorption ionization mass spectrometry: application to kidney biology. Semin. Nephrol. 2007 Nov; 27(6): 597-608. PMID: 18061842, PMCID: PMC2180835, PII: S0270-9295(07)00124-6, DOI: 10.1016/j.semnephrol.2007.09.002, ISSN: 0270-9295.

Yildiz PB, Shyr Y, Rahman JS, Wardwell NR, Zimmerman LJ, Shakhtour B, Gray WH, Chen S, Li M, Roder H, Liebler DC, Bigbee WL, Siegfried JM, Weissfeld JL, Gonzalez AL, Ninan M, Johnson DH, Carbone DP, Caprioli RM, Massion PP. Diagnostic accuracy of MALDI mass spectrometric analysis of unfractionated serum in lung cancer. J Thorac Oncol. 2007 Oct; 2(10): 893-901. PMID: 17909350, PMCID: PMC4220686, PII: 01243894-200710000-00004, DOI: 10.1097/JTO.0b013e31814b8be7, ISSN: 1556-1380.

Cornett DS, Reyzer ML, Chaurand P, Caprioli RM. MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat. Methods. 2007 Oct; 4(10): 828-33. PMID: 17901873, PII: nmeth1094, DOI: 10.1038/nmeth1094, ISSN: 1548-7091.

McLean JA, Ridenour WB, Caprioli RM. Profiling and imaging of tissues by imaging ion mobility-mass spectrometry. J Mass Spectrom. 2007 Aug; 42(8): 1099-105. PMID: 17621390, DOI: 10.1002/jms.1254, ISSN: 1076-5174.

Chaurand P, Schriver KE, Caprioli RM. Instrument design and characterization for high resolution MALDI-MS imaging of tissue sections. J Mass Spectrom. 2007 Apr; 42(4): 476-89. PMID: 17328093, DOI: 10.1002/jms.1180, ISSN: 1076-5174.

M'Koma AE, Blum DL, Norris JL, Koyama T, Billheimer D, Motley S, Ghiassi M, Ferdowsi N, Bhowmick I, Chang SS, Fowke JH, Caprioli RM, Bhowmick NA. Detection of pre-neoplastic and neoplastic prostate disease by MALDI profiling of urine. Biochem. Biophys. Res. Commun [print-electronic]. 2007 Feb 2/16/2007; 353(3): 829-34. PMID: 17194448, PMCID: PMC2562600, PII: S0006-291X(06)02787-2, DOI: 10.1016/j.bbrc.2006.12.111, ISSN: 0006-291X.

Groseclose MR, Andersson M, Hardesty WM, Caprioli RM. Identification of proteins directly from tissue: in situ tryptic digestions coupled with imaging mass spectrometry. J Mass Spectrom. 2007 Feb; 42(2): 254-62. PMID: 17230433, DOI: 10.1002/jms.1177, ISSN: 1076-5174.

Reyzer ML, Caprioli RM. MALDI-MS-based imaging of small molecules and proteins in tissues. Curr Opin Chem Biol [print-electronic]. 2007 Feb; 11(1): 29-35. PMID: 17185024, PII: S1367-5931(06)00191-8, DOI: 10.1016/j.cbpa.2006.11.035, ISSN: 1367-5931.

Friedman DB, Wang SE, Whitwell CW, Caprioli RM, Arteaga CL. Multivariable difference gel electrophoresis and mass spectrometry: a case study on transforming growth factor-beta and ERBB2 signaling. Mol. Cell Proteomics [print-electronic]. 2007 Jan; 6(1): 150-69. PMID: 17028091, PII: D600001-MCP200, DOI: 10.1074/mcp.D600001-MCP200, ISSN: 1535-9476.

Massion PP, Caprioli RM. Proteomic strategies for the characterization and the early detection of lung cancer. J Thorac Oncol. 2006 Nov; 1(9): 1027-39. PMID: 17409991, PII: 01243894-200611000-00019, ISSN: 1556-1380.

Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM. New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J. Proteome Res. 2006 Nov; 5(11): 2889-900. PMID: 17081040, DOI: 10.1021/pr060346u, ISSN: 1535-3893.

Cornett DS, Mobley JA, Dias EC, Andersson M, Arteaga CL, Sanders ME, Caprioli RM. A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Mol. Cell Proteomics [print-electronic]. 2006 Oct; 5(10): 1975-83. PMID: 16849436, PII: M600119-MCP200, DOI: 10.1074/mcp.M600119-MCP200, ISSN: 1535-9476.

Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM. Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spectrometry. Anal. Chem. 2006 Sep 9/15/2006; 78(18): 6448-56. PMID: 16970320, DOI: 10.1021/ac060788p, ISSN: 0003-2700.

Amann JM, Chaurand P, Gonzalez A, Mobley JA, Massion PP, Carbone DP, Caprioli RM. Selective profiling of proteins in lung cancer cells from fine-needle aspirates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin. Cancer Res. 2006 Sep 9/1/2006; 12(17): 5142-50. PMID: 16951232, PII: 12/17/5142, DOI: 10.1158/1078-0432.CCR-06-0264, ISSN: 1078-0432.

Chaurand P, Cornett DS, Caprioli RM. Molecular imaging of thin mammalian tissue sections by mass spectrometry. Curr. Opin. Biotechnol [print-electronic]. 2006 Aug; 17(4): 431-6. PMID: 16781865, PII: S0958-1669(06)00086-3, DOI: 10.1016/j.copbio.2006.06.002, ISSN: 0958-1669.

Suzuki K, Yu X, Chaurand P, Araki Y, Lareyre JJ, Caprioli RM, Matusik RJ, Orgebin-Crist MC. Epididymis-specific promoter-driven gene targeting: a transcription factor which regulates epididymis-specific gene expression. Mol. Cell. Endocrinol [print-electronic]. 2006 May 5/16/2006; 250(1-2): 184-9. PMID: 16414179, PII: S0303-7207(05)00489-2, DOI: 10.1016/j.mce.2005.12.043, ISSN: 0303-7207.

Luka Z, Ham AJ, Norris JL, Yeo EJ, Yermalitsky V, Glenn B, Caprioli RM, Liebler DC, Wagner C. Identification of phosphorylation sites in glycine N-methyltransferase from rat liver. Protein Sci [print-electronic]. 2006 Apr; 15(4): 785-94. PMID: 16522797, PMCID: PMC2242492, PII: ps.051906706, DOI: 10.1110/ps.051906706, ISSN: 0961-8368.

Sköld K, Svensson M, Nilsson A, Zhang X, Nydahl K, Caprioli RM, Svenningsson P, Andrén PE. Decreased striatal levels of PEP-19 following MPTP lesion in the mouse. J. Proteome Res. 2006 Feb; 5(2): 262-9. PMID: 16457591, DOI: 10.1021/pr050281f, ISSN: 1535-3893.

Aerni HR, Cornett DS, Caprioli RM. Automated acoustic matrix deposition for MALDI sample preparation. Anal. Chem. 2006 Feb 2/1/2006; 78(3): 827-34. PMID: 16448057, DOI: 10.1021/ac051534r, ISSN: 0003-2700.

Rahman SM, Shyr Y, Yildiz PB, Gonzalez AL, Li H, Zhang X, Chaurand P, Yanagisawa K, Slovis BS, Miller RF, Ninan M, Miller YE, Franklin WA, Caprioli RM, Carbone DP, Massion PP. Proteomic patterns of preinvasive bronchial lesions. Am. J. Respir. Crit. Care Med [print-electronic]. 2005 Dec 12/15/2005; 172(12): 1556-62. PMID: 16179643, PMCID: PMC2718455, PII: 200502-274OC, DOI: 10.1164/rccm.200502-274OC, ISSN: 1073-449X.

Caprioli RM. Deciphering protein molecular signatures in cancer tissues to aid in diagnosis, prognosis, and therapy. Cancer Res. 2005 Dec 12/1/2005; 65(23): 10642-5. PMID: 16322204, PII: 65/23/10642, DOI: 10.1158/0008-5472.CAN-04-3581, ISSN: 0008-5472.

Xie L, Xu BJ, Gorska AE, Shyr Y, Schwartz SA, Cheng N, Levy S, Bierie B, Caprioli RM, Moses HL. Genomic and proteomic analysis of mammary tumors arising in transgenic mice. J. Proteome Res. 2005 Nov; 4(6): 2088-98. PMID: 16335954, DOI: 10.1021/pr050214l, ISSN: 1535-3893.

Norris JL, Hangauer MJ, Porter NA, Caprioli RM. Nonacid cleavable detergents applied to MALDI mass spectrometry profiling of whole cells. J Mass Spectrom. 2005 Oct; 40(10): 1319-26. PMID: 16220468, DOI: 10.1002/jms.914, ISSN: 1076-5174.

Xu BJ, Shyr Y, Liang X, Ma LJ, Donnert EM, Roberts JD, Zhang X, Kon V, Brown NJ, Caprioli RM, Fogo AB. Proteomic patterns and prediction of glomerulosclerosis and its mechanisms. J. Am. Soc. Nephrol [print-electronic]. 2005 Oct; 16(10): 2967-75. PMID: 16079267, PII: ASN.2005030262, DOI: 10.1681/ASN.2005030262, ISSN: 1046-6673.

Zimmerman LJ, Wernke GR, Caprioli RM, Liebler DC. Identification of protein fragments as pattern features in MALDI-MS analyses of serum. J. Proteome Res. 2005 Sep; 4(5): 1672-80. PMID: 16212420, DOI: 10.1021/pr050138m, ISSN: 1535-3893.

Schwartz SA, Weil RJ, Thompson RC, Shyr Y, Moore JH, Toms SA, Johnson MD, Caprioli RM. Proteomic-based prognosis of brain tumor patients using direct-tissue matrix-assisted laser desorption ionization mass spectrometry. Cancer Res. 2005 Sep 9/1/2005; 65(17): 7674-81. PMID: 16140934, PII: 65/17/7674, DOI: 10.1158/0008-5472.CAN-04-3016, ISSN: 0008-5472.

Laurent C, Levinson DF, Schwartz SA, Harrington PB, Markey SP, Caprioli RM, Levitt P. Direct profiling of the cerebellum by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: A methodological study in postnatal and adult mouse. J. Neurosci. Res. 2005 Sep 9/1/2005; 81(5): 613-21. PMID: 16035104, DOI: 10.1002/jnr.20590, ISSN: 0360-4012.

Hu X, Friedman D, Hill S, Caprioli R, Nicholson W, Powers AC, Hunter L, Limbird LE. Proteomic exploration of pancreatic islets in mice null for the alpha2A adrenergic receptor. J. Mol. Endocrinol. 2005 Aug; 35(1): 73-88. PMID: 16087723, PII: 35/1/73, DOI: 10.1677/jme.1.01764, ISSN: 0952-5041.

Norris JL, Porter NA, Caprioli RM. Combination detergent/MALDI matrix: functional cleavable detergents for mass spectrometry. Anal. Chem. 2005 Aug 8/1/2005; 77(15): 5036-40. PMID: 16053319, DOI: 10.1021/ac050460g, ISSN: 0003-2700.

Gao N, Ishii K, Mirosevich J, Kuwajima S, Oppenheimer SR, Roberts RL, Jiang M, Yu X, Shappell SB, Caprioli RM, Stoffel M, Hayward SW, Matusik RJ. Forkhead box A1 regulates prostate ductal morphogenesis and promotes epithelial cell maturation. Development [print-electronic]. 2005 Aug; 132(15): 3431-43. PMID: 15987773, PII: dev.01917, DOI: 10.1242/dev.01917, ISSN: 0950-1991.

Reyzer ML, Caprioli RM. MALDI mass spectrometry for direct tissue analysis: a new tool for biomarker discovery. J. Proteome Res. 2005 Jul; 4(4): 1138-42. PMID: 16083264, DOI: 10.1021/pr050095+, ISSN: 1535-3893.

Crecelius AC, Cornett DS, Caprioli RM, Williams B, Dawant BM, Bodenheimer B. Three-dimensional visualization of protein expression in mouse brain structures using imaging mass spectrometry. J. Am. Soc. Mass Spectrom. 2005 Jul; 16(7): 1093-9. PMID: 15923124, PII: S1044-0305(05)00203-5, DOI: 10.1016/j.jasms.2005.02.026, ISSN: 1044-0305.

Caldwell RL, Caprioli RM. Tissue profiling by mass spectrometry: a review of methodology and applications. Mol. Cell Proteomics [print-electronic]. 2005 Apr; 4(4): 394-401. PMID: 15677390, PII: R500006-MCP200, DOI: 10.1074/mcp.R500006-MCP200, ISSN: 1535-9476.

Ma S, Hill KE, Burk RF, Caprioli RM. Mass spectrometric determination of selenenylsulfide linkages in rat selenoprotein P. J Mass Spectrom. 2005 Mar; 40(3): 400-4. PMID: 15712351, DOI: 10.1002/jms.801, ISSN: 1076-5174.

Chaurand P, Schwartz SA, Reyzer ML, Caprioli RM. Imaging mass spectrometry: principles and potentials. Toxicol Pathol. 2005; 33(1): 92-101. PMID: 15805060, PII: XQJ862EEDFCJJE65, DOI: 10.1080/01926230590881862, ISSN: 0192-6233.

Reyzer ML, Caldwell RL, Dugger TC, Forbes JT, Ritter CA, Guix M, Arteaga CL, Caprioli RM. Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics. Cancer Res. 2004 Dec 12/15/2004; 64(24): 9093-100. PMID: 15604278, PII: 64/24/9093, DOI: 10.1158/0008-5472.CAN-04-2231, ISSN: 0008-5472.

Chaurand P, Sanders ME, Jensen RA, Caprioli RM. Proteomics in diagnostic pathology: profiling and imaging proteins directly in tissue sections. Am. J. Pathol. 2004 Oct; 165(4): 1057-68. PMID: 15466373, PMCID: PMC3118833, PII: S0002-9440(10)63367-6, DOI: 10.1016/S0002-9440(10)63367-6, ISSN: 0002-9440.

Chaurand P, Schwartz SA, Caprioli RM. Assessing protein patterns in disease using imaging mass spectrometry. J. Proteome Res. 2004 Mar; 3(2): 245-52. PMID: 15113100, ISSN: 1535-3893.

Friedman DB, Hill S, Keller JW, Merchant NB, Levy SE, Coffey RJ, Caprioli RM. Proteome analysis of human colon cancer by two-dimensional difference gel electrophoresis and mass spectrometry. Proteomics. 2004 Mar; 4(3): 793-811. PMID: 14997500, DOI: 10.1002/pmic.200300635, ISSN: 1615-9853.

Chaurand P, Schwartz SA, Billheimer D, Xu BJ, Crecelius A, Caprioli RM. Integrating histology and imaging mass spectrometry. Anal. Chem. 2004 Feb 2/15/2004; 76(4): 1145-55. PMID: 14961749, DOI: 10.1021/ac0351264, ISSN: 0003-2700.

Schwartz SA, Weil RJ, Johnson MD, Toms SA, Caprioli RM. Protein profiling in brain tumors using mass spectrometry: feasibility of a new technique for the analysis of protein expression. Clin. Cancer Res. 2004 Feb 2/1/2004; 10(3): 981-7. PMID: 14871976, ISSN: 1078-0432.

Norris JL, Porter NA, Caprioli RM. Mass spectrometry of intracellular and membrane proteins using cleavable detergents. Anal. Chem. 2003 Dec 12/1/2003; 75(23): 6642-7. PMID: 14640740, DOI: 10.1021/ac034802z, ISSN: 0003-2700.

Chaurand P, Fouchécourt S, DaGue BB, Xu BJ, Reyzer ML, Orgebin-Crist MC, Caprioli RM. Profiling and imaging proteins in the mouse epididymis by imaging mass spectrometry. Proteomics. 2003 Nov; 3(11): 2221-39. PMID: 14595821, DOI: 10.1002/pmic.200300474, ISSN: 1615-9853.

Reyzer ML, Hsieh Y, Ng K, Korfmacher WA, Caprioli RM. Direct analysis of drug candidates in tissue by matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom. 2003 Oct; 38(10): 1081-92. PMID: 14595858, DOI: 10.1002/jms.525, ISSN: 1076-5174.

Yanagisawa K, Xu BJ, Carbone DP, Caprioli RM. Molecular fingerprinting in human lung cancer. Clin Lung Cancer. 2003 Sep; 5(2): 113-8. PMID: 14596694, PII: S1525-7304(11)70329-1, DOI: 10.3816/CLC.2003.n.025, ISSN: 1525-7304.

Ma S, Hill KE, Burk RF, Caprioli RM. Mass spectrometric identification of N- and O-glycosylation sites of full-length rat selenoprotein P and determination of selenide-sulfide and disulfide linkages in the shortest isoform. Biochemistry. 2003 Aug 8/19/2003; 42(32): 9703-11. PMID: 12911312, DOI: 10.1021/bi0346300, ISSN: 0006-2960.

Yanagisawa K, Shyr Y, Xu BJ, Massion PP, Larsen PH, White BC, Roberts JR, Edgerton M, Gonzalez A, Nadaf S, Moore JH, Caprioli RM, Carbone DP. Proteomic patterns of tumour subsets in non-small-cell lung cancer. Lancet. 2003 Aug 8/9/2003; 362(9382): 433-9. PMID: 12927430, PII: S0140-6736(03)14068-8, DOI: 10.1016/S0140-6736(03)14068-8, ISSN: 1474-547X.

Schwartz SA, Reyzer ML, Caprioli RM. Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. J Mass Spectrom. 2003 Jul; 38(7): 699-708. PMID: 12898649, DOI: 10.1002/jms.505, ISSN: 1076-5174.

Ma S, Caprioli RM, Hill KE, Burk RF. Loss of selenium from selenoproteins: conversion of selenocysteine to dehydroalanine in vitro. J. Am. Soc. Mass Spectrom. 2003 Jun; 14(6): 593-600. PMID: 12781460, PII: S1044030503001417, DOI: 10.1016/S1044-0305(03)00141-7, ISSN: 1044-0305.

Zhen Y, Caprioli RM, Staros JV. Characterization of glycosylation sites of the epidermal growth factor receptor. Biochemistry. 2003 May 5/13/2003; 42(18): 5478-92. PMID: 12731890, PMCID: PMC2765783, DOI: 10.1021/bi027101p, ISSN: 0006-2960.

Fouchécourt S, Lareyre JJ, Chaurand P, DaGue BB, Suzuki K, Ong DE, Olson GE, Matusik RJ, Caprioli RM, Orgebin-Crist MC. Identification, immunolocalization, regulation, and postnatal development of the lipocalin EP17 (epididymal protein of 17 kilodaltons) in the mouse and rat epididymis. Endocrinology. 2003 Mar; 144(3): 887-900. PMID: 12586765, DOI: 10.1210/en.2002-220932, ISSN: 0013-7227.

Phillip Hochgesang G, Nemeth-Cawley JF, Rowlinson SW, Caprioli RM, Marnett LJ. Functional analysis of the molecular determinants of cyclooxygenase-2 acetylation by 2-acetoxyphenylhept-2-ynyl sulfide. Arch. Biochem. Biophys. 2003 Jan 1/1/2003; 409(1): 127-33. PMID: 12464251, PII: S0003986102005490, ISSN: 0003-9861.

Xu BJ, Caprioli RM, Sanders ME, Jensen RA. Direct analysis of laser capture microdissected cells by MALDI mass spectrometry. J. Am. Soc. Mass Spectrom. 2002 Nov; 13(11): 1292-7. PMID: 12443019, DOI: 10.1016/S1044-0305(02)00644-X, ISSN: 1044-0305.

Chaurand P, Schwartz SA, Caprioli RM. Imaging mass spectrometry: a new tool to investigate the spatial organization of peptides and proteins in mammalian tissue sections. Curr Opin Chem Biol. 2002 Oct; 6(5): 676-81. PMID: 12413553, PII: S1367593102003708, ISSN: 1367-5931.

Chaurand P, Caprioli RM. Direct profiling and imaging of peptides and proteins from mammalian cells and tissue sections by mass spectrometry. Electrophoresis. 2002 Sep; 23(18): 3125-35. PMID: 12298084, DOI: 10.1002/1522-2683(200209)23:18<3125::AID-ELPS3125>3.0.CO;2-#, ISSN: 0173-0835.

Boutaud O, Ou JJ, Chaurand P, Caprioli RM, Montine TJ, Oates JA. Prostaglandin H2 (PGH2) accelerates formation of amyloid beta1-42 oligomers. J. Neurochem. 2002 Aug; 82(4): 1003-6. PMID: 12358806, PII: 1064, ISSN: 0022-3042.

Ma S, Hill KE, Caprioli RM, Burk RF. Mass spectrometric characterization of full-length rat selenoprotein P and three isoforms shortened at the C terminus. Evidence that three UGA codons in the mRNA open reading frame have alternative functions of specifying selenocysteine insertion or translation termination. J. Biol. Chem [print-electronic]. 2002 Apr 4/12/2002; 277(15): 12749-54. PMID: 11821412, PII: M111462200, DOI: 10.1074/jbc.M111462200, ISSN: 0021-9258.

Fouchécourt S, Chaurand P, DaGue BB, Lareyre JJ, Matusik RJ, Caprioli RM, Orgebin-Crist MC. Epididymal lipocalin-type prostaglandin D2 synthase: identification using mass spectrometry, messenger RNA localization, and immunodetection in mouse, rat, hamster, and monkey. Biol. Reprod. 2002 Feb; 66(2): 524-33. PMID: 11804971, ISSN: 0006-3363.

Chaurand P, DaGue BB, Pearsall RS, Threadgill DW, Caprioli RM. Profiling proteins from azoxymethane-induced colon tumors at the molecular level by matrix-assisted laser desorption/ionization mass spectrometry. Proteomics. 2001 Oct; 1(10): 1320-6. PMID: 11721643, DOI: 10.1002/1615-9861(200110)1:10<1320::AID-PROT1320>3.0.CO;2-G, ISSN: 1615-9853.

Chaurand P, DaGue BB, Ma S, Kasper S, Caprioli RM. Strain-based sequence variations and structure analysis of murine prostate specific spermine binding protein using mass spectrometry. Biochemistry. 2001 Aug 8/14/2001; 40(32): 9725-33. PMID: 11583173, ISSN: 0006-2960.

Boutaud O, Brame CJ, Chaurand P, Li J, Rowlinson SW, Crews BC, Ji C, Marnett LJ, Caprioli RM, Roberts LJ, Oates JA. Characterization of the lysyl adducts of prostaglandin H-synthases that are derived from oxygenation of arachidonic acid. Biochemistry. 2001 Jun 6/12/2001; 40(23): 6948-55. PMID: 11389610, PII: bi002629k, ISSN: 0006-2960.

Hondal RJ, Ma S, Caprioli RM, Hill KE, Burk RF. Heparin-binding histidine and lysine residues of rat selenoprotein P. J. Biol. Chem [print-electronic]. 2001 May 5/11/2001; 276(19): 15823-31. PMID: 11278668, PII: M010405200, DOI: 10.1074/jbc.M010405200, ISSN: 0021-9258.

Stoeckli M, Chaurand P, Hallahan DE, Caprioli RM. Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues. Nat. Med. 2001 Apr; 7(4): 493-6. PMID: 11283679, PII: 86573, DOI: 10.1038/86573, ISSN: 1078-8956.

Miller MA, Nguyen VQ, Lee MH, Kosinski M, Schedl T, Caprioli RM, Greenstein D. A sperm cytoskeletal protein that signals oocyte meiotic maturation and ovulation. Science. 2001 Mar 3/16/2001; 291(5511): 2144-7. PMID: 11251118, PII: 291/5511/2144, DOI: 10.1126/science.1057586, ISSN: 0036-8075.

Nemeth JF, Hochgesang GP, Marnett LJ, Caprioli RM. Characterization of the glycosylation sites in cyclooxygenase-2 using mass spectrometry. Biochemistry. 2001 Mar 3/13/2001; 40(10): 3109-16. PMID: 11258925, PII: bi002313c, ISSN: 0006-2960.

Masumori N, Thomas TZ, Chaurand P, Case T, Paul M, Kasper S, Caprioli RM, Tsukamoto T, Shappell SB, Matusik RJ. A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res. 2001 Mar 3/1/2001; 61(5): 2239-49. PMID: 11280793, ISSN: 0008-5472.

Nguyen VQ, Caprioli RM, Cover TL. Carboxy-terminal proteolytic processing of Helicobacter pylori vacuolating toxin. Infect. Immun. 2001 Jan; 69(1): 543-6. PMID: 11119549, PMCID: PMC97915, DOI: 10.1128/IAI.69.1.543-546.2001, ISSN: 0019-9567.

Stoeckli, M, Chaurand, P, Hallahan, DE, Caprioli, RM. Imaging Mass Spectrometry: A New Technique Applied to Mammalian Brain Tumor Protein Expression. Nature Medicine. 2001; 7: 493-6.

Miller, M.A., Nguyen, V.Q., Lee, M-H, Kosinski, M., Schedl, T., Caprioli, R.M., Greenstein, D. A Sperm Cytoskeletal Protein that Signals Oocyte Meiotic Maturation and Ovulation. Science. 2001; 291: 2144-7.

Nemeth, JF, Hochgesang, Jr., GP, Marnett, LJ, Caprioli, RM. Characterization of the Glycosylation Sites in Cyclooxygenase-2 Using Mass Spectrometry. Biochemistry. 2001; 10: 3109.

Todd, P.J., Schaaff, T.G., Chaurand, P., and Caprioli, R.M. Organic Ion Imaging of Biological Tissue with MALDI and SIMS. J. Mass Spectrom.. 2001; 36((4)): 355-69.

Boutaud, O., Brame, C.J., Chaurand, P., Li, J., Rowlinson, S.W., Crews, B.C., Ji, C., Marnett, L.J., Caprioli, R.M., Roberts, LJ II, Oates, J.A. Characterization of the Lysyl-Adducts of Prostaglandin H-Synthases that are Derived from Oxygenation of Arachidonic Acid. Biochemistry. 2001; 40((23)): 6948-55.

Chaurand, P., DaGue, B.B., Pearsall, R. S., Threadgill, D.W., Caprioli, R.M. Profiling Proteins from Azoxymethane-induced Colon Tumors at the Molecular Level by MALDI Mass Spectrometry. Proteomics. 2001; 1: 1320-6.

Koomen, J.M., Stoeckli, M., and Caprioli, R.M. Mapping of surrogate markers of cellular components and structures using laser desorption mass spectrometry. J. Mass Spectrom. 2000; 35: 258-564.

Chaurand P, Stoeckli M, Caprioli RM. Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal. Chem. 1999 Dec 12/1/1999; 71(23): 5263-70. PMID: 10596208, ISSN: 0003-2700.

Zhang H, Stoeckli M, Andren PE, Caprioli RM. Combining solid-phase preconcentration, capillary electrophoresis and off-line matrix-assisted laser desorption/ionization mass spectrometry: intracerebral metabolic processing of peptide E in vivo. J Mass Spectrom. 1999 Apr; 34(4): 377-83. PMID: 10226364, PII: 10.1002/(SICI)1096-9888(199904)34:4<377::AID-JMS778>3.0.CO;2-D, DOI: 10.1002/(SICI)1096-9888(199904)34:4<377::AID-JMS778>3.0.CO;2-D, ISSN: 1076-5174.

Schlunegger UP, Stoeckli M, Caprioli RM. Frequency scan for the analysis of high mass ions generated by matrix-assisted laser desorption/ionization in a paul trap. Rapid Commun. Mass Spectrom. 1999; 13(18): 1792-6. PMID: 10482890, PII: 10.1002/(SICI)1097-0231(19990930)13:18<1792::AID-RCM715>3.0.CO;2-S, DOI: 10.1002/(SICI)1097-0231(19990930)13:18<1792::AID-RCM715>3.0.CO;2-S, ISSN: 1097-0231.

Stoeckli M, Farmer TB, Caprioli RM. Automated mass spectrometry imaging with a matrix-assisted laser desorption ionization time-of-flight instrument. J. Am. Soc. Mass Spectrom. 1999 Jan; 10(1): 67-71. PMID: 9888186, PII: S1044-0305(98)00126-3, DOI: 10.1016/S1044-0305(98)00126-3, ISSN: 1044-0305.

Chaurand, P., Stoeckli, M. and Caprioli, R.M. Direct Profiling of Proteins in Biological Tissue Sections by MALDI Mass Spectrometry. Anal Chem. 1999; 71: 5263-70.

Stoeckli, M., Farmer, T.B., and Caprioli, R.M. Automated MS imaging with a MALDI TOF instrument. J. Am. Soc. Mass Spectrom. 1999; 10((1)): 67-71.

Zhang, H., Stoeckli, M., Andren, P.E., and Caprioli, R.M. Combining solid phase preconcentration, capillary electrophoresis, and imaging matrix-assisted laser desorption ionization mass spectrometry: Intracerebral metabolic processing of peptide E in vivo. J. Mass Spectrom. 1999; 342: 377-83.

Andren, P.E., and Caprioli, R.M. Determination of extracellular release of neurotensin rat brain regions utilizing in vivo microdialysis/electrospray mass spectrometry. Brian Research. 1999; 845: 123-9.

Farmer TB, Caprioli RM. Determination of protein-protein interactions by matrix-assisted laser desorption/ionization mass spectrometry. J Mass Spectrom. 1998 Aug; 33(8): 697-704. PMID: 9786710, PII: 10.1002/(SICI)1096-9888(199808)33:8<697::AID-JMS711>3.0.CO;2-H, DOI: 10.1002/(SICI)1096-9888(199808)33:8<697::AID-JMS711>3.0.CO;2-H, ISSN: 1076-5174.

Andren, P.E., Emmett, M.R., DaGue, B.B., Steulet, A.-F., Waldmeier, P., and Caprioli, R.M. Blood-brain barrier penetration of 3-aminopropyl-n-butylphosphinic acid (CGP 36742) in rat brain by microdialysis/mass spectrometry. J. Mass Spectrom. 1998; 33: 281-7.

Farmer, T.B., and Caprioli, R.M. Determination of protein-protein interactions by matrix-assisted laser desorption/ionization mass spectrometry. J. Mass Spectrom. 1998; 33((8)): 697-704.

Caprioli, R. M., Farmer, T. B., and Gile, J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Analytical Chemistry. 1997; 69: 4751-60.

Zhang, H., and Caprioli, R.M. Capillary electrophoresis combined with matrix-assisted laser desorption ionization mass spectrometry: Continuous sample deposition on a matrix-precoated membrane target. J. Mass Spectrom. 1996; 31: 1039-46.

Sanderson, K., Andren, P.E., Caprioli, R.M., and Nyberg, F. In vitro metabolism of LVV-hemorphin-7 in human plasma studied by reversed-phase high-performance liquid chromatography and micro-electrospray mass spectrometry. J. Chromatogr. 1996; 743: 207-12.

Eriksson, U., Andren, P.E., Caprioli, R.M., and Nyberg, F. Reversed-phase high-performance liquid chromatography combined with tandem mass spectrometry in studies of a substance P-converting enzyme from human cerebrospinal fluid. J. Chromatogr. 1996; 743: 213-20.

Emmett, M.R., Andren, P.E., and Caprioli, R.M. Specific molecular mass detection of endogenously released neuropeptides using in vivo microdialysis/mass spectrometry. J. Neuroscience. 1995; 62: 141-7.

Farmer, T.B., and Caprioli, R.M. Mass discrimination in MALDI TOF MS: A study using crosslinked oligomeric complexes. J. Mass Spectrom. 1995; 30: 1245-54.

Andren, P.E., and Caprioli, R.M. In vivo metabolism of substance P in rat striatum utilizing microdialysis/liquid chromatography/micro-electrospray mass spectrometry. J. Mass Spectrom. 1995; 30: 817-24.

Zhang, H., Andren, P.E., and Caprioli, R.M. Micro-preparation procedure for high sensitivity matrix-assisted laser desorption ionization mass spectrometry. J. Mass Spectrom. 1995; 30: 1768-71.

Lecchi, P., and Caprioli, R.M. Matrix-assisted laser desorption mass spectrometry for peptide mapping. New Methods in Peptide Mapping for the Characterization of Proteins, (Ed. W.S. Hancock), CRC Press, Inc., Boca Raton, FL. 1995; 219-40.

Caprioli, R.M. and Suter, M. J.-F. Mass Spectrometry. Introduction to Biophysical Methods, (Eds., J.A. Glasel and M.P. Deutscher), Academic Press Inc., Orlando, FL. 1995; 147-204.

Lin, S.-N., Slopis, J.M., Butler, I.J., and Caprioli, R.M. In vivo microdialysis and gas chromatography/mass spectrometry for studies on release of N-acetylaspartylglutamate and N-acetylaspartate in rat brain hypothalamus. J. Neurosci. Methods. 1995; 62: 199-205.

Andren, P.E., Lin, S.-N., and Caprioli, R.M. Microdialysis/mass spectrometry. Mass Spectrometry: Clinical and Biomedical Applications, Vol. 2 (D.M. Desiderio, ed), Plenum Publish. Corp., New York. 1994; 237-54.

Caprioli, R.M. On-line LC/MS and CE/MS. Biological Mass Spectrometry: Present and Future, (Eds. T. Matsuo, R.M. Caprioli, M.L. Gross and Y. Seyama), John Wiley & Sons Ltd., Sussex, UK. 1994; 75-100.

Andren, P.E., and Caprioli, R.M. Microdialysis/mass spectrometry of neuropeptides. Biological Mass Spectrometry: Present and Future, (Eds. T. Matsuo, R.M. Caprioli, M. Gross, and Y. Seyama), John Wiley & Sons Ltd., Sussex, UK. 1994; 355-67.

Emmett, M.R., and Caprioli, R.M. Micro-electrospray MS: Ultra-high-sensitivity analysis of peptides and proteins. J. Am. Soc. Mass Spectrom. 1994; 54: 605-13.

Andren, P.E., Emmett, M.R., and Caprioli, R.M. Micro-electrospray: Zeptomole/attomole per microliter sensitivity for peptides. J. Am. Soc. Mass Spectrom. 1994; 5: 867-9.

Farmer, T.B., and Caprioli, R.M. Assessing the multimeric states of proteins by matrix-assisted laser desorption mass spectrometry: comparison with other biochemical methods. Techniques in Protein Chemistry IV, (Ed. R.H. Angeletti), Academic Press, Inc. San Diego, CA. 1993; 73-81.

Caprioli, R.M., and Wu, A.H.B. Mass Spectrom. Anal. Chem. Review. 1993; 65((12)): 470R-474R.

Suter, M.J.-F., and Caprioli, R.M. An integral probe for capillary zone electrophoresis/continuous-flow fast atom bombardment mass spectrometry. JASMS. 1992; 30: 198-206.

Suter, M.J.-F, Moore, W.T., Farmer, T.B., Cottrell, J.S., and Caprioli, R.M. Analysis of protein-protein binding with laser desorption mass spectrometry: Can multimeric forms be studied?. Techniques in Protein Chemistry III, (Ed. R.H. Angeletti), Academic Press, Inc., Orlando, F. 1992; 447-445.

Caprioli, R.M., and Suter, M.J.-F. Continuous-flow fast atom bombardment: Recent advances and applications. Int. J. Mass Spectrom. and Ion Processes. 1992; 118/119: 449-76.

Farmer, T.B., and Caprioli, R.M. Assessing the multimeric states of proteins: Studies using laser desorption mass spectrometry. BMS. 1991; 20: 796-800.

Suter, M.J.-F., DaGue, B.B., Lin, S-N, and Caprioli, R.M. Recent advances in LC/MS and CZE/MS for protein analysis. J. Chromatogr. 1991; 553: 101-16.

Caprioli, R.M. Continuous-flow fast atom bombardment mass spectrometry: Direct analysis of polar and ionic compounds in aqueous solutions. Anal. Chem. 1990; 62: 477-85.

Caprioli, R.M. Continuous-flow fast atom bombardment mass spectrometry. Biochem. CLin. 1990; 14: 1302-10.