{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:04:30Z","timestamp":1790816670434,"version":"4.1.0"},"reference-count":46,"publisher":"SPIE-Intl Soc Optical Eng","issue":"03","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Biomed. Opt."],"published-print":{"date-parts":[[2003,7,1]]},"abstract":"<jats:p>Sulfur mustard (SM; 2,2-dichloroethyl sulfide) is a percutaneous alkylating agent first used as a chemical weapon at Ypres, Belgium, in World War I. Despite its well-documented history, the primary lesions effecting dermal\u2013epidermal separation and latent onset of incapacitating blisters remain poorly understood. By immunofluorescent imaging of human epidermal keratinocytes (HEK) and epidermal tissues exposed to SM (400 \u03bcM for 5 min), we have amassed unequivocal evidence that SM disrupts adhesion complex molecules, which are also disrupted by epidermolysis bullosa-type blistering diseases of the skin. Images of keratin 14 (K14) in control cells showed tentlike filament networks linking the HEK's basolateral anchoring sites to the dorsal surface of its nuclei. Images from 6-h postexposure profiles revealed early disruption (\u2264 1 h) and progressive collapse of the K14 cytoskeleton. Collapse involved focal erosions, loss of functional asymmetry, and displacement of nuclei beneath a mat of jumbled filaments. In complementary studies, 1-h images showed statistically significant (p&lt;0.01) decreases of 25 to 30% in emissions from labeled \u03b16\u03b24 integrin and laminin 5, plus disruption of their receptor\u2013ligand organization. Results indicate that SM alkylation destabilizes dermal\u2013epidermal attachments and potentiates vesication by disrupting adhesion complex molecules and associated signaling mechanisms required for their maintenance and repair.<\/jats:p>","DOI":"10.1117\/1.1584687","type":"journal-article","created":{"date-parts":[[2003,7,24]],"date-time":"2003-07-24T18:29:15Z","timestamp":1059071355000},"page":"396-409","source":"Crossref","is-referenced-by-count":14,"title":["Multiphoton microscopy: an optical approach to understanding and resolving sulfur mustard lesions"],"prefix":"10.1117","volume":"8","author":[{"given":"Robert J.","family":"Werrlein","sequence":"first","affiliation":[{"name":"U.S. Army Medical Research Institute of Infectious"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janna S.","family":"Madren-Whalley","sequence":"additional","affiliation":[{"name":"U.S. Army Medical Research Inst of Chemical Def"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"189","reference":[{"key":"10.1117\/1.1584687_r1","doi-asserted-by":"crossref","unstructured":"W. Denk, D. Piston, and W. Webb, \u201cTwo-photon molecular excitation in laser-scanning microscopy,\u201d Chapter 28 in\n                      Handbook of Biological Confocal Microscopy\n                      , J. Pawley, Ed., pp. 445\u2013458, Plenum, New York (1995).","DOI":"10.1007\/978-1-4757-5348-6_28"},{"key":"10.1117\/1.1584687_r2","doi-asserted-by":"crossref","unstructured":"P. T. C. So, K. H. Kim, C. Buehler, B. R. Masters, L. Hsu, and C. Y. Dong, \u201cBasic principles of multiphoton excitation microscopy,\u201d Chapter 9 in\n                      Methods in Cellular Imaging\n                      , A. Periasamy, Ed., pp. 147\u2013161, Oxford University Press, New York (2001).","DOI":"10.1007\/978-1-4614-7513-2_9"},{"key":"10.1117\/1.1584687_r3","doi-asserted-by":"crossref","unstructured":"V. P. Wallace, A. K. Dunn, M. O. Coleno, and B. Tromberg, \u201cTwo-photon microscopy in highly scattering tissue,\u201d Chapter 11 in\n                      Methods in Cellular Imaging\n                      , A. Periasamy, Ed., pp. 180\u2013199, Oxford University Press, New York (2001).","DOI":"10.1007\/978-1-4614-7513-2_11"},{"key":"10.1117\/1.1584687_r4","unstructured":"B. Papirmeister, A. Feister, S. Robinson, and R. Ford,\n                      Medical Defense Against Mustard Gas: Toxic Mechanisms and Pharmacological Implications\n                      , CRC Press, Boca Raton, FL (1991)."},{"key":"10.1117\/1.1584687_r5","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1083\/jcb.115.6.1661","volume":"115","author":"Coulombe","year":"1991","journal-title":"J. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9525","issn-type":"print"},{"key":"10.1117\/1.1584687_r6","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1101\/gad.8.21.2574","volume":"8","author":"Chan","year":"1994","journal-title":"Genes Dev.","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"key":"10.1117\/1.1584687_r7","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/1523-1747.ep12342985","volume":"106","author":"Chan","year":"1996","journal-title":"J. Invest. Dermatol.","ISSN":"https:\/\/id.crossref.org\/issn\/0022-202X","issn-type":"print"},{"key":"10.1117\/1.1584687_r8","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0923-1811(96)00568-3","volume":"13","author":"Fuchs","year":"1996","journal-title":"J. Dermatol. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/0923-1811","issn-type":"print"},{"key":"10.1117\/1.1584687_r9","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1091\/mbc.8.2.189","volume":"8","author":"Fuchs","year":"1997","journal-title":"Mol. Biol. Cell","ISSN":"https:\/\/id.crossref.org\/issn\/1059-1524","issn-type":"print"},{"key":"10.1117\/1.1584687_r10","first-page":"197","volume":"30","author":"Fuchs","year":"1996","journal-title":"Annu. Rev. Genet.","ISSN":"https:\/\/id.crossref.org\/issn\/0066-1497","issn-type":"print"},{"key":"10.1117\/1.1584687_r11","doi-asserted-by":"crossref","first-page":"S115","DOI":"10.1002\/1099-1263(200012)20:1+<::AID-JAT682>3.0.CO;2-Q","volume":"20","author":"Werrlein","year":"2000","journal-title":"J. Appl. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0260-437X","issn-type":"print"},{"key":"10.1117\/1.1584687_r12","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1117\/12.470695","volume":"4620","author":"Werrlein","year":"2002","journal-title":"Proc. SPIE","ISSN":"https:\/\/id.crossref.org\/issn\/0277-786X","issn-type":"print"},{"key":"10.1117\/1.1584687_r13","doi-asserted-by":"crossref","first-page":"9079","DOI":"10.1073\/pnas.93.17.9079","volume":"93","author":"Uttam","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U.S.A.","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"key":"10.1117\/1.1584687_r14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1126\/science.279.5350.514","volume":"279","author":"Fuchs","year":"1998","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"10.1117\/1.1584687_r15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/BF00767494","volume":"11","author":"Zhang","year":"1995","journal-title":"Cell Biol. Toxicol.","ISSN":"https:\/\/id.crossref.org\/issn\/0742-2091","issn-type":"print"},{"key":"10.1117\/1.1584687_r16","doi-asserted-by":"crossref","unstructured":"R. J. Werrlein and J. S. Madren-Whalley, \u201cImaging sulfur mustard lesions in basal cells and human epidermal tissues by confocal and multiphoton laser-scanning microscopy,\u201d Chapter 27 in\n                      Alternative Toxicological Methods\n                      , H. S. Salem and S. Katz, Eds., pp. 303\u2013312, CRC Press, Boca Raton, FL (2003).","DOI":"10.1201\/9780203008799.ch27"},{"key":"10.1117\/1.1584687_r17","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1091\/mbc.4.9.871","volume":"4","author":"Spinardi","year":"1993","journal-title":"Mol. Biol. Cell","ISSN":"https:\/\/id.crossref.org\/issn\/1059-1524","issn-type":"print"},{"key":"10.1117\/1.1584687_r18","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1083\/jcb.106.3.723","volume":"106","author":"Foisner","year":"1988","journal-title":"J. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9525","issn-type":"print"},{"key":"10.1117\/1.1584687_r19","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1006\/jsbi.1995.1055","volume":"115","author":"Foisner","year":"1995","journal-title":"J. Struct. Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/1047-8477","issn-type":"print"},{"key":"10.1117\/1.1584687_r20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0014-4827(84)90766-3","volume":"155","author":"Wiche","year":"1984","journal-title":"Exp. Cell Res.","ISSN":"https:\/\/id.crossref.org\/issn\/0014-4827","issn-type":"print"},{"key":"10.1117\/1.1584687_r21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1083\/jcb.121.3.607","volume":"121","author":"Wiche","year":"1993","journal-title":"J. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9525","issn-type":"print"},{"key":"10.1117\/1.1584687_r22","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1046\/j.1523-1747.1998.00452.x","volume":"111","author":"Hopkinson","year":"1998","journal-title":"J. Invest. Dermatol.","ISSN":"https:\/\/id.crossref.org\/issn\/0022-202X","issn-type":"print"},{"key":"10.1117\/1.1584687_r23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(95)90333-X","volume":"81","author":"Guo","year":"1995","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"key":"10.1117\/1.1584687_r24","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1242\/jcs.109.10.2509","volume":"109","author":"Baker","year":"1996","journal-title":"J. Cell. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9533","issn-type":"print"},{"key":"10.1117\/1.1584687_r25","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/(SICI)1521-1878(199806)20:6<488::AID-BIES7>3.0.CO;2-I","volume":"21","author":"Jones","year":"1998","journal-title":"BioEssays","ISSN":"https:\/\/id.crossref.org\/issn\/0265-9247","issn-type":"print"},{"key":"10.1117\/1.1584687_r26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1600-0625.1998.tb00304.x","volume":"7","author":"Pulkkinen","year":"1998","journal-title":"Exp. Dermatol.","ISSN":"https:\/\/id.crossref.org\/issn\/0906-6705","issn-type":"print"},{"key":"10.1117\/1.1584687_r27","doi-asserted-by":"crossref","unstructured":"R. Werrlein, T. Hamilton, and J. S. Madren-Whalley, \u201cDevelopment of human keratinocyte colonies for confocal microscopy and for study of calcium effects on growth differentiation and sulfur mustard lesions,\u201d Chapter 14 in\n                      Toxicity Assessment Alternatives: Methods, Issues, Opportunities\n                      , H. Salem and S. Katz, Eds., pp. 165\u2013174, Humana Press, Totowa, NJ (1999).","DOI":"10.1007\/978-1-59259-718-5_14"},{"key":"10.1117\/1.1584687_r28","unstructured":"J. F. Dillman III, K. L. McGary, and J. S. Schlager, \u201cSulfur mustard-induced high molecular weight aggregates of keratins K5 and K14 in human epidermal keratinocytes,\u201d (submitted)."},{"key":"10.1117\/1.1584687_r29","doi-asserted-by":"crossref","first-page":"E101","DOI":"10.1038\/ncb0402-e101","volume":"4","author":"Jamora","year":"2002","journal-title":"Nat. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/1465-7392","issn-type":"print"},{"key":"10.1117\/1.1584687_r30","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"key":"10.1117\/1.1584687_r31","unstructured":"G. Delwel and A. Sonnenberg, \u201cLaminin isoforms and their integrin receptors,\u201d Chapter 2 in\n                      Adhesion Receptors as Therapeutic Targets\n                      , M. A. Horton, Ed., pp. 9\u201336, CRC Press, Boca Raton, FL (1996)."},{"key":"10.1117\/1.1584687_r32","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.1002\/j.1460-2075.1995.tb00126.x","volume":"14","author":"Mainiero","year":"1995","journal-title":"EMBO J.","ISSN":"https:\/\/id.crossref.org\/issn\/0261-4189","issn-type":"print"},{"key":"10.1117\/1.1584687_r33","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1101\/gad.14.9.1027","volume":"14","author":"Pawson","year":"2000","journal-title":"Genes Dev.","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"key":"10.1117\/1.1584687_r34","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1242\/jcs.114.14.2553","volume":"114","author":"Schwartz","year":"2001","journal-title":"J. Cell. Sci.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9533","issn-type":"print"},{"key":"10.1117\/1.1584687_r35","unstructured":"M. Mol, \u201cSulfur mustard induces low molecular weight fragments of keratin 14 in human epidermal keratinocytes,\u201d (in preparation)."},{"key":"10.1117\/1.1584687_r36","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0955-0674(96)80106-2","volume":"8","author":"Borradori","year":"1996","journal-title":"Curr. Opin. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0955-0674","issn-type":"print"},{"key":"10.1117\/1.1584687_r37","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0945-053X(98)00003-1","volume":"18","author":"Nievers","year":"1999","journal-title":"Matrix Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0945-053X","issn-type":"print"},{"key":"10.1117\/1.1584687_r38","doi-asserted-by":"crossref","first-page":"8970","DOI":"10.1073\/pnas.87.22.8970","volume":"87","author":"Stepp","year":"1990","journal-title":"Proc. Natl. Acad. Sci. U.S.A.","ISSN":"https:\/\/id.crossref.org\/issn\/0027-8424","issn-type":"print"},{"key":"10.1117\/1.1584687_r39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/excr.1994.1166","volume":"213","author":"Jones","year":"1994","journal-title":"Exp. Cell Res.","ISSN":"https:\/\/id.crossref.org\/issn\/0014-4827","issn-type":"print"},{"key":"10.1117\/1.1584687_r40","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0955-0674(97)80118-4","volume":"9","author":"Burgeson","year":"1997","journal-title":"Curr. Opin. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0955-0674","issn-type":"print"},{"key":"10.1117\/1.1584687_r41","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1083\/jcb.134.2.559","volume":"134","author":"Dowling","year":"1996","journal-title":"J. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0021-9525","issn-type":"print"},{"key":"10.1117\/1.1584687_r42","first-page":"77","volume":"1242","author":"Rosales","year":"1995","journal-title":"Biochem. Biophys. Acta"},{"key":"10.1117\/1.1584687_r43","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1046\/j.1523-1747.1999.00546.x","volume":"112","author":"Borradori","year":"1999","journal-title":"J. Invest. Dermatol.","ISSN":"https:\/\/id.crossref.org\/issn\/0022-202X","issn-type":"print"},{"key":"10.1117\/1.1584687_r44","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/87569","volume":"8","author":"Takagi","year":"2001","journal-title":"Nat. Struct. Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/1072-8368","issn-type":"print"},{"key":"10.1117\/1.1584687_r45","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0092-8674(02)00935-2","volume":"110","author":"Takagi","year":"2002","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"key":"10.1117\/1.1584687_r46","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/S0955-0674(99)80037-4","volume":"11","author":"Schoenwaelder","year":"1999","journal-title":"Curr. Opin. Cell Biol.","ISSN":"https:\/\/id.crossref.org\/issn\/0955-0674","issn-type":"print"}],"container-title":["Journal of Biomedical Optics"],"original-title":[],"link":[{"URL":"https:\/\/www.spiedigitallibrary.org\/journals\/journal-of-biomedical-optics\/volume-8\/issue-03\/396\/Multiphoton-microscopy--an-optical-approach-to-understanding-and-resolving\/10.1117\/1.1584687.full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:26:38Z","timestamp":1790814398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.spiedigitallibrary.org\/journals\/journal-of-biomedical-optics\/volume-8\/issue-03\/396\/Multiphoton-microscopy--an-optical-approach-to-understanding-and-resolving\/10.1117\/1.1584687.full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,7,1]]},"references-count":46,"journal-issue":{"issue":"03"},"URL":"https:\/\/doi.org\/10.1117\/1.1584687","relation":{},"ISSN":["1083-3668","1560-2281"],"issn-type":[{"value":"1083-3668","type":"print"},{"value":"1560-2281","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,7,1]]}}}