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Structure and Function of the Nail Unit

  • Philip Fleckman
  • Lauren McCaffrey
Chapter

Abstract

This chapter reviews the embryology and development, anatomy and cell biology, physiology, biochemistry, biophysics, and pharmacology of the nail unit.

Keywords

Nail unit Nail plate Nail structure Function Anatomy 

Notes

Acknowledgements

Robert Underwood and Marcia Usui assisted in creation of ◘ Figs. 5.1 and 5.3. Jan Biesbroeck assisted in creation of ◘ Fig. 5.6. Dale Davis created ◘ Fig. 5.8 based on the work of Dr. Andrew Morgan.

References

  1. 1.
    Pinkus F. Der Nagel. In: Jadassohn J, editor. New York: Springer; 1927. p. 266–89.Google Scholar
  2. 2.
    Rainey E. On the structure and formation of the nails of the fingers and toes. Trans Microsc Socof Lond. 1849;2:105–9.CrossRefGoogle Scholar
  3. 3.
    Unna PG. In: Ziemessen, editor. Entwichtlungsgeschichte und anatomy. Leipzig: Vogel, F.C.W.; 1883. p. 38–51.Google Scholar
  4. 4.
    Zaias N. The nail in health and disease. Norwalk: Appleton & Lange; 1990.Google Scholar
  5. 5.
    Lewis BL. Microscopic studies of fetal and mature nail and surrounding soft tissue. AMA Arch Dermatol Syph. 1954;70:732–47.CrossRefGoogle Scholar
  6. 6.
    Zaias N. Embryology of the human nail. Arch Dermatol. 1963;87:77–93.CrossRefGoogle Scholar
  7. 7.
    Hashimoto K, Gross BG, Nelson R, Lever WF. The ultrastructure of the skin of human embryos: III. The formation of the nail in 16–18 weeks old embryos. J Invest Dermatol. 1966;47:205–17.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Holbrook KA. Human epidermal embryogenesis. Int J Dermatol. 1979;18:329–56.PubMedCrossRefGoogle Scholar
  9. 9.
    Holbrook KA. Structural abnormalities of the epidermally derived appendaages in skin from patients with ectodermal dysplasia: insight into developmental errors. Recent advances in ectodermal dysplasia. Birth Defects Orig Artic Ser. 1988;24:15–44.PubMedGoogle Scholar
  10. 10.
    Holbrook KA. In: Goldsmith LA, editor. Structure and function of the developing human skin physiology, biochemistry, and molecular biology of the skin. New York: Oxford University Press; 1991. p. 63–110.Google Scholar
  11. 11.
    Zaias N. Onychomycosis. Arch Dermatol. 1972;105:263–74.PubMedCrossRefGoogle Scholar
  12. 12.
    Runne U, Orfanos CE. The human nail. Curr Probl Dermatol. 1981;9:102–49.PubMedCrossRefGoogle Scholar
  13. 13.
    Tickle C. Molecular basis of vertebrate limb patterning. Am J Med Genet. 2002;112:250–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen H, Johnson RL. Dorsoventral patterning of the vertebrate limb: a process governed by multiple events. Cell Tissue Res. 1999;296:67–73.PubMedCrossRefGoogle Scholar
  15. 15.
    Capecchi MR. Hox genes and mammalian development. Cold Spring Harb Symp Quant Biol. 1997;62:273–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Clough MV, Hamlington JD, McIntosh I. Restricted distribution of loss-of-function mutations within the LMX1B genes of nail-patella syndrome patients. Hum Mutat. 1999;14:459–65.PubMedCrossRefGoogle Scholar
  17. 17.
    Jumlongras D, Bei M, Stimson JM, et al. A nonsense mutation in MSX1 causes Witkop syndrome. Am J Hum Genet. 2001;69:67–74.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Frojmark AS, Schuster J, Sobol M, et al. Mutations in Frizzled 6 cause isolated autosomal-recessive nail dysplasia. Am J Hum Genet. 2011;88:852–60.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Naz G, Pasternack SM, Perrin C, et al. FZD6 encoding the Wnt receptor frizzled-6 is mutated in autosomal-recessive nail dysplasia. Br J Dermatol. 2012;166:1088.PubMedCrossRefGoogle Scholar
  20. 20.
    Potter CS, Pruett ND, Kern MJ, et al. The nude mutant gene Foxn1 is a HOXC13 regulatory target during hair follicle and nail differentiation. J Invest Dermatol. 2011;131:828–37.PubMedCrossRefGoogle Scholar
  21. 21.
    Cai J, Ma L. Msx2 and Foxn1 regulate nail homeostasis. Genesis. 2011;49:449–59.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Forslind B. Biophysical studies of the normal nail. Acta Dermatovenerol. 1970;50:161–8.Google Scholar
  23. 23.
    Caputo R, Dadati E. Preliminary observations about the ultrastructure of the human nail plate treated with thioglycolic acid. Archiv Klin Exp Dermatol. 1968;231:344–54.CrossRefGoogle Scholar
  24. 24.
    Forslind B, Thyresson N. On the structure of the normal nail: a scanning electron microscopic study. Arch Derm Forsch. 1975;251:199–204.CrossRefGoogle Scholar
  25. 25.
    Hamilton JB, Terada H, Mestler GE. Studies of growth throughout the lifespan in Japanese: growth and size of nails and their relationship to age, heredity and other factors. J Gerontol. 1955;10:401–15.PubMedCrossRefGoogle Scholar
  26. 26.
    Finlay AY, Moseley H, Duggan TC. Ultrasound transmission time: an in vivo guide to nail thickness. Br J Dermatol. 1987;117:765–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Geyer AS, Onumah N, Uyttendaele H, Scher RK. Modulation of linear nail growth to treat diseases of the nail. J Am Acad Dermatol. 2004;50:229–34.PubMedCrossRefGoogle Scholar
  28. 28.
    Germann H, Barran W, Plewig G. Morphology of corneocytes from human nail plates. J Invest Dermatol. 1980;74:115–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Brody I. The keratinization of epidermal cells of normal guinea pig skin as revealed by electron microscopy. J Ultrastruct Res. 1959;2:482–511.CrossRefGoogle Scholar
  30. 30.
    Hashimoto K. Ultrastructure of the human toenail. Cell migration, keratinization, and formation of the intercellular cement. Arch Derm Forsch. 1971;240:1–22.CrossRefGoogle Scholar
  31. 31.
    Hashimoto K. Ultrastructure of the human toenail. II. Keratinization and formation of the marginal band. J Ultrastr Res. 1971;36:391–410.CrossRefGoogle Scholar
  32. 32.
    Stenn K, Fleckman P. Hair and nail physiology. In: Hordinsky MK, Scher RK, editors. Atlas of hair and nails. Philadelphia: Churchill Livingstone; 2000. p. 3–8.Google Scholar
  33. 33.
    Perrin C. Expression of follicular sheath keratins in the normal nail with special reference to the morphological analysis of the distal nail unit. Am J Dermatopathol. 2007;29:543–50.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Walters KA, Flynn GL, Marvel JR. Physiocochemical characterization of the human nail: I. Pressure sealed appratus for measuring nail plate permeabilities. J Invest Dermatol. 1981;76:76–9.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Clark WELG. Nails. In: Press C, editor. Tissues of the body. Oxford: Clarendan Press; 1965. p. 315–9.Google Scholar
  36. 36.
    Kitahara T, Ogawa H. Cultured nail keratinocytes express hard keratins characteristic of nail and hair in vivo. Nature. 1992;284:253–6.Google Scholar
  37. 37.
    Picardo M, Tosti A, Marchese C, et al. Characterization of cultured nail matrix cells. J Am Acad Dermatol. 1994;30:434–40.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Kazi R, Moghaddam S, Chu P, Marghoob AA. Histologic evidence of melanocytes isolated to the nail matrix. JAMA Dermatol. 2016;152:573–5.CrossRefPubMedGoogle Scholar
  39. 39.
    Perrin C, Michiels JF, Pisani A, Ortonne JP. Anatomic distribution of melanocytes in normal nail unit: an immunohistochemical investigation. Am J Dermatopathol. 1997;19:462–7.CrossRefPubMedGoogle Scholar
  40. 40.
    Tosti A, Cameli N, Piraccini BM, Fanti PA, Ortonne JP. Characterization of nail matrix melanocytes with anti-PEP1, anti-PEP8, TMH-1, and HMB-45 antibodies. J Am Acad Dermatol. 1994;31:193–6.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Amin B, Nehal KS, Jungbluth AA, et al. Histologic distinction between subungual lentigo and melanoma. Am J Surg Pathol. 2008;32:835–43.PubMedCrossRefGoogle Scholar
  42. 42.
    Perrin C. Tumors of the nail unit. A review. Part I: acquired localized longitudinal melanonychia and erythronychia. Am J Dermatopathol. 2013;35:621–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Higashi N, Saito T. Horizontal distribution of the dopa-positive melanocytes in the nail matrix. J Invest Dermatol. 1969;53:163–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Hashimoto K. Ultrastructure of the human toenail. I. Proximal nail matrix. J Invest Dermatol. 1971;56:235–46.PubMedCrossRefGoogle Scholar
  45. 45.
    Stern DK, Creasey AA, Quijije J, Lebwohl MG. UV-A and UV-B penetration of normal human cadaveric fingernail plate. Arch Dermatol. 2011;147:439–41.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Hashimoto K. The ultrastructure of the skin of human embryos. X. Merkel tactile cells in the finger and nail. J Anat. 1972;111:99–120.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Cameli N, Ortonne JP, Picardo M, Peluso AM, Tosti A. Distribution of Merkel cells in adult human nail matrix [letter]. Br J Dermatol. 1998;139:541.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Ito T, Ito N, Saathoff M, et al. Immunology of the human nail apparatus: the nail matrix is a site of relative immune privilege. J Invest Dermatol. 2005;125:1139–48.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Clark WELG. The problem of the claw in primates. Proc Zool Soc. 1936;1:1–24.Google Scholar
  50. 50.
    Burrows MT. The significance of the lunula of the nail. Johns Hopkins Hosp Rep. 1919;18:357–61.Google Scholar
  51. 51.
    Lewin K. The normal finger nail. Br J Dermatol. 1965;77:421–30.CrossRefPubMedGoogle Scholar
  52. 52.
    Samman PD, Fenton DA. Samman’s the nails in disease. London: Butterworth-Heinemann; 1995.Google Scholar
  53. 53.
    Drape JL, Wolfram-Gabel R, Idy-Peretti I, et al. The lunula: a magnetic resonance imaging approach to the subnail matrix area. J Invest Dermatol. 1996;106:1081–5.PubMedCrossRefGoogle Scholar
  54. 54.
    Wolfram-Gabel R, Sick H. Vascular networks of the periphery of the fingernail. J Hand Surg. 1995;20B:488–92.CrossRefGoogle Scholar
  55. 55.
    Mitchell JC. A clinical study of leukonychia. Br J Dermatol. 1953;65:121–30.PubMedCrossRefGoogle Scholar
  56. 56.
    Martin BF, Platts MM. A histological study of the nail region in normal human subjects and in those showing splinter hemorrhages of the nail. J Anat. 1959;93:323.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Montagna W, Parakkal PF. The structure and function of skin. 3rd ed. New York: Academic.Google Scholar
  58. 58.
    Rand R, Baden HP. Pathophysiology of nails-onychopathophysiology. In: Soter NA, Baden HP, editors. Pathophysiology of dermatologic diseases. New York: McGraw-Hill; 1991. p. 209.Google Scholar
  59. 59.
    Zaias N. The regeneration of the primate nail studies of the squirrel monkey, Saimiri. J Invest Dermatol. 1965;44:107–17.CrossRefPubMedGoogle Scholar
  60. 60.
    Fleckman P, Omura EF. Histopathology of the nail. Adv Dermatol. 2001;17:385–406.PubMedGoogle Scholar
  61. 61.
    Terry RB. The onychodermal band in health and disease. Lancet. 1955;I:179–81.CrossRefGoogle Scholar
  62. 62.
    Stewart WK, Raffle EJ. Brown nail-bed arcs and chronic renal disease. Br Med J. 1972;1:784–6.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Holzberg M, Walker HK. Terry’s nails revisited: revised definition and new correlations. Lancet. 1984;I:896–9.CrossRefGoogle Scholar
  64. 64.
    Lindsay PG. The half-and-half nail. Arch Intern Med. 1967;119:583–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Raffle EJ. Terry’s nails. Lancet. 1984;I:1131.CrossRefGoogle Scholar
  66. 66.
    Sonnex TS, Griffiths WAD, Nicol WJ. The nature and significance of the transverse white band of human nails. Semin Dermatol. 1991;10:12–6.PubMedGoogle Scholar
  67. 67.
    Sinclair RD, Wojnarowska F, Leigh IM, Dawber RPR. The basement membrane zone of the nail. Br J Dermatol. 1994;131:499–505.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Lee DY, Yang JM, Mun GH, Jang KT, Cho KH. Immunohistochemical study of specialized nail mesenchyme containing onychofibroblasts in transverse sections of the nail unit. Am J Dermatopathol. 2011;33:266–70.PubMedCrossRefGoogle Scholar
  69. 69.
    Lee DY, Park JH, Shin HT, et al. The presence and localization of onychodermis (specialized nail mesenchyme) containing onychofibroblasts in the nail unit: a morphological and immunohistochemical study. Histopathology. 2012;61:123–30.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Kelikian H. Congenital deformities of the hand. Philadelphia: W.B. Saunders.Google Scholar
  71. 71.
    Baran R, Juhlin L. Bone dependent nail formation. Br J Dermatol. 1986;114:371.PubMedCrossRefGoogle Scholar
  72. 72.
    Takeo M, Chou WC, Sun Q, et al. Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature. 2013;499:228–32.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Flint MH. Some observations on the vascular supply of the nail bed and terminal segments of the finger. Br J Plast Surg. 1955;8:186–95.PubMedCrossRefGoogle Scholar
  74. 74.
    Hale AR, Burch GE. The arteriovenous anastomoses and blood vessles of the human finger. Medicine. 1960;39:191–240.PubMedCrossRefGoogle Scholar
  75. 75.
    Samman PD. The human toenail: its genesis and blood supply. Br J Dermatol. 1959;71:296–302.PubMedCrossRefGoogle Scholar
  76. 76.
    Hasegawa M. Dermoscopy findings of nail fold capillaries in connective tissue diseases. J Dermatol. 2011;38:66–70.PubMedCrossRefGoogle Scholar
  77. 77.
    Kabasakal Y, Elvins DM, Ring EF, McHugh NJ. Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls. Ann Rheum Dis. 1996;55:507–12.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Fleckman P, Allan C. Surgical anatomy of the nail unit. Dermatol Surg. 2001;27:257–60.PubMedGoogle Scholar
  79. 79.
    Seah BZ, Wu CC, Sebastin SJ, Lahiri A. Tactile sensibility on the fingernail. J Hand Surg. 2013;38:2159–63.CrossRefGoogle Scholar
  80. 80.
    Bean WB. A note on fingernail growth. J Invest Dermatol. 1953;20:27–31.PubMedCrossRefGoogle Scholar
  81. 81.
    Bean WB. Nail growth: 30 years of observation. Arch Intern Med. 1974;134:497–502.PubMedCrossRefGoogle Scholar
  82. 82.
    Dawber R, Baran R. Nail growth. Cutis. 1987;39:99–103.PubMedGoogle Scholar
  83. 83.
    Vellar OD. Composition of human nail substance. Am J Clin Nutr. 1970;23:1272–4.PubMedCrossRefGoogle Scholar
  84. 84.
    Dawber R. Fingernail growth in normal and psoriatic subjects. Br J Dermatol. 1970;82:454–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Clark WELG, Buxton LHD. Studies in nail growth. Br J Dermatol. 1938;50:221–35.CrossRefGoogle Scholar
  86. 86.
    Halban J, Spitzer MZ. Uber das gesteigerte wachstum der nagel in der schwangerschaft. Monatsschrift fur Geburtshulfe und Gynakologie. 1929;82:25–31.Google Scholar
  87. 87.
    Hillman RW. Fingernail growth in pregnancy relations to some common parameters of the reproductive process. Hum Biol. 1960;323:119–34.Google Scholar
  88. 88.
    Geoghegan B, Roberts DF, Sampford MR. Possible climatic effect on nail growth. J Appl Physiol. 1958;13:135–8.PubMedCrossRefGoogle Scholar
  89. 89.
    Dawber RPR, Samman PD, Bottoms E. Fingernail growth in idiopathic and psoriatic onycholysis. Br J Dermatol. 1971;85:558–60.PubMedCrossRefGoogle Scholar
  90. 90.
    Orentreich N, Markofsky J, Vogelman JH. The effect of aging on the rate of linear nail growth. J Invest Dermatol. 1979;73:126–30.PubMedCrossRefGoogle Scholar
  91. 91.
    Head H, Sherren J. The consequence of injury to the peripheral nerves in man. Brain. 1919;28:263–75.Google Scholar
  92. 92.
    Gilchrist ML, Buxton LHD. The relation of finger-nail growth to nutritional status. J Anat. 1939;73:575–82.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Samman PD, White WF. The “yellow nail” syndrome. Br J Dermatol. 1964;76:153–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Basler VA. Wachstumsvorgange am vollentwickelten organismus (growth processes in fully developed organisms). Med Klin. 1937;33:1664–6.Google Scholar
  95. 95.
    Bean WB. Nail growth: twenty-five years’ observation. Arch Intern Med. 1968;122:359–61.PubMedCrossRefGoogle Scholar
  96. 96.
    Sibinga MS. Observations on growth of fingernails in health and disease. Pediatrics. 1959;24:225–33.PubMedGoogle Scholar
  97. 97.
    Baran R, Dawber RPR, De Berker DAR, et al. Diseases of the nails and their management. 4th ed. Oxford: Blackwell Scientific Publications; 2012.Google Scholar
  98. 98.
    Norton LA. Incorporation of thymidine-methyl-H3 and glycine-2-H3 in the nail matrix and bed of humans. J Invest Dermatol. 1971;56:61–8.CrossRefPubMedGoogle Scholar
  99. 99.
    Jarrett A, Spearman RIC. The histochemistry of the human nail. Arch Dermatol. 1966;94:652–7.CrossRefPubMedGoogle Scholar
  100. 100.
    Garson JC, Baltenneck F, Leroy F, Riekel C, Muller M. Histological structure of human nail as studied by synchrotron X-ray microdiffraction. Cell MolBiol(Noisy-le-grand). 2000;46:1025–34.Google Scholar
  101. 101.
    Johnson M, Comaish JS, Shuster S. Nail is produced by the normal nail bed: a controversy resolved. Br J Dermatol. 1991;125:27–9.PubMedCrossRefGoogle Scholar
  102. 102.
    Johnson M, Shuster S. Continuous formation of nail along the bed. Br J Dermatol. 1993;128:277–80.PubMedCrossRefGoogle Scholar
  103. 103.
    Zaias N, Alvarez J. The formation of the primate nail plate. An autoradiographic study in squirrel monkey. J Invest Dermatol. 1968;51:120–36.CrossRefPubMedGoogle Scholar
  104. 104.
    Forslind B, Lindstrom B, Philipson B. Quantitative microradiography of normal human nail. Acta Dermatovenerol. 1971;51:89–92.Google Scholar
  105. 105.
    Forslind B, Wroblewski R, Afzelius BA. Calcium and sulfur location in human nail. J Invest Dermatol. 1976;67:273–5.PubMedCrossRefGoogle Scholar
  106. 106.
    Robson JRK, Brooks GJ. The distribution of calcium in fingernails from healthy and malnourished children. Clin Chim Acta. 1974;55:255–7.PubMedCrossRefGoogle Scholar
  107. 107.
    De Berker D, Wojnarowska F, Sviland L, Westgate GE, Dawber RP, Leigh IM. Keratin expression in the normal nail unit: markers of regional differentiation. Br J Dermatol. 2000;142:89–96.PubMedCrossRefGoogle Scholar
  108. 108.
    Samman PD. The ventral nail. Arch Dermatol. 1961;84:192–5.CrossRefGoogle Scholar
  109. 109.
    De Berker D, Mawhinney B, Sviland L. Quantification of regional matrix nail production. Br J Dermatol. 1996;134:1083–6.PubMedCrossRefGoogle Scholar
  110. 110.
    Kligman AM. Why do nails grow out instead of up? Arch Dermatol. 1961;84:181–3.Google Scholar
  111. 111.
    Baran R. Nail growth direction revisited. J Am Acad Dermatol. 1981;4:78–83.CrossRefPubMedGoogle Scholar
  112. 112.
    Kikuchi I, Ogata K, Idemori M. Vertically growing ectopic nail. J Am Acad Dermatol. 1984;10:114–6.PubMedCrossRefGoogle Scholar
  113. 113.
    Kligman AM. Response. J Am Acad Dermatol. 1981;4:82–3.CrossRefGoogle Scholar
  114. 114.
    Silver H, Chiego B. Nails and nail changes. II. Modern concepts of anatomy and biochemistry of the nails. J Invest Dermatol. 1940;3:133–42.CrossRefGoogle Scholar
  115. 115.
    Krantz W. Beitrag zur anatomie des nagels. Dermatol Zeitschrift. 1932;64:239–42.CrossRefGoogle Scholar
  116. 116.
    Kligman AM. Nails. In: Pillsbury DM, editor. Dermatology. Philadelphia: W. B. Saunders; 1956. p. 32–9.Google Scholar
  117. 117.
    Zaias N. The movement of the nail bed. J Invest Dermatol. 1967;48:402–3.CrossRefPubMedGoogle Scholar
  118. 118.
    Bank HL, Robson J, Bigelow JB, Morrison J, Spell LH, Kantor R. Preparation of fingernails for trace element analysis. Clin Chim Acta. 1981;116:179–90.PubMedCrossRefGoogle Scholar
  119. 119.
    Goldblum RW, Derby S, Lerner AB. The metal content of skin, nails and hair. J Invest Dermatol. 1953;20:13–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Harrison WW, Clemena GG. Survey analysis of trace elements in human fingernails by spark source mass spectrometry. Clin Chim Acta. 1972;36:485–92.PubMedCrossRefGoogle Scholar
  121. 121.
    Kanabrocki E, Case LF, Graham LA, Fields T, Oester YT, Kaplan E. Neutron-activation studies of trace elements in human fingernail. J Nucl Med. 1968;9:478–81.PubMedGoogle Scholar
  122. 122.
    Harrison WW, Tyree AB. The determination of trace elements in human fingernails by atomic absorption spectroscopy. Clin Chim Acta. 1971;31:63–73.PubMedCrossRefGoogle Scholar
  123. 123.
    GM M. Copper content of hair and nails of normal individuals and of patients with hepatolenticular degeneration. Nature. 1964;202:903–4.CrossRefGoogle Scholar
  124. 124.
    Jacobs A, Jenkins DJ. The iron content of finger nails. Br J Dermatol. 1970;72:145–8.CrossRefGoogle Scholar
  125. 125.
    Djaldetti M, Fishman P, Hart J. The iron content of finger-nails in iron deficient patients. Clin Sci. 1987;72:669–72.PubMedCrossRefGoogle Scholar
  126. 126.
    Leonard PJ, Morris WP, Brown R. Sodium, potassium, calcium and magnesium contents in nails of children with kwashiorkor. Biochem J. 1968;110:22P–3P.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Bock H, Koch E, Stephan U, Windorfer A, Sitzmann FC, Grosse H. Investigations on electrolyte concentrations in the nails of cystic fibrosis patients and controls. Mod Probl Pediatr. 1967;10:279–83.Google Scholar
  128. 128.
    Kopito L, Mahmoodian A, Townley RRW, Khaw KT, Shwachman H. Studies in cystic fibrosis. NEJM. 1965;272:504–9.PubMedCrossRefGoogle Scholar
  129. 129.
    Whitford GM, Sampaio FC, Arneberg P, der Fehr FR. Fingernail fluoride: a method for monitoring fluoride exposure. Caries Res. 1999;33:462–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Lander H, Hodge PR, Crisp CS. Arsenic in the hair and nails. J Forensic Med. 1965;12:52–67.PubMedGoogle Scholar
  131. 131.
    Shapiro HA. Arsenic content of human hair and nails: its interpretation. J Forensic Med. 1967;14:65–71.PubMedGoogle Scholar
  132. 132.
    Mandal BK, Ogra Y, Suzuki KT. Speciation of arsenic in human nail and hair from arsenic-affected area by HPLC-inductively coupled argon plasma mass spectrometry. Toxicol Appl Pharmacol. 2003;189:73–83.PubMedCrossRefGoogle Scholar
  133. 133.
    Daniel CR 3rd, Piraccini BM, Tosti A. The nail and hair in forensic science. J Am Acad Dermatol. 2004;50:258–61.PubMedCrossRefGoogle Scholar
  134. 134.
    Klauder JV, Brown H. Sulphur content of hair and of nails in abnormal states. II Nails. Arch Dermatol Syphil. 1935;31:26–34.CrossRefGoogle Scholar
  135. 135.
    Lockard D, Pass R, Cassady G. Fingernail nitrogen content in neonates. Pediatrics. 1972;49:618–20.PubMedGoogle Scholar
  136. 136.
    Hein K, Cohen MI, McNamara H. Racial differences in nitrogen content of nails among adolescents. Am J Clin Nutr. 1977;30:496–8.PubMedCrossRefGoogle Scholar
  137. 137.
    Hess WC. Variations in amino acid content of finger nails of normal and arthritic individuals. J Biol Chem. 1935;109:xliii.Google Scholar
  138. 138.
    Grozdanovic J, Ulbert K. Oscillopolarographic determination of cysteic acid level in the fingernails followed chronic irradiation in humans. Strahlentherapie. 1970;139:735–7.PubMedGoogle Scholar
  139. 139.
    Pruzanski W, Arnon R. Determination of cystine and other amino acids in the fingernails of members of various ethnic groups in Israel. Israel J Med Sci. 1966;2:465–7.PubMedGoogle Scholar
  140. 140.
    Jalili MA, Al-Kassab S. Koilonychia and cystine content of nails. Lancet. 1959;III:108–10.CrossRefGoogle Scholar
  141. 141.
    Fraser RDB. Keratins. Sci Amer. 1969;221:86–96.PubMedCrossRefGoogle Scholar
  142. 142.
    Coulombe PA, Ma L, Yamada S, Wawersik M. Intermediate filaments at a glance. J Cell Sci. 2001;114:4345–7.PubMedGoogle Scholar
  143. 143.
    Baden HP, Goldsmith LA, Fleming B. A comparative study of the physiocochemical proterties of human keratinized tissues. Biochem Biophys Acta. 1973;322:269–78.PubMedGoogle Scholar
  144. 144.
    Baden HP, Kubilus J. A comparative study of the immunologic properties of hoof and nail fibrous proteins. J Invest Dermatol. 1984;83:327–31.PubMedCrossRefGoogle Scholar
  145. 145.
    Powell BC, Rogers GE. Differentiation in hard keratin tissues: hair and related structures. In: Leigh IM, Lane EB, Watt FM, editors. The keratinocyte handbook. Cambridge: Cambridge University Press; 1994. p. 401–36.Google Scholar
  146. 146.
    Lynch MH, O'Guinn WM, Hardy C, Mak L, Sun TT. Acidic and basic hair/nail (“hard”) keratins: their colocalization in upper cortical and cuticle cells of the human hair follicle and their relationship to “soft” keratins. J Cell Biol. 1986;103:2593–606.PubMedCrossRefGoogle Scholar
  147. 147.
    Fuchs E. Keratins: mechanical integrators in the epidermis and hair and their role in disease. Prog Dermatol. 1996;30:1–12.Google Scholar
  148. 148.
    Hesse M, Magin TM, Weber K. Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18. J Cell Sci. 2001;114:2569–75.PubMedGoogle Scholar
  149. 149.
    Wang Z, Wong P, Langbein L, Schweizer J, Coulombe PA. Type II epithelial keratin 6hf (K6hf) is expressed in the companion layer, matrix, and medulla in anagen-stage hair follicles. J Invest Dermatol. 2003;121:1276–82.PubMedCrossRefGoogle Scholar
  150. 150.
    Wojcik SM, Longley MA, Roop DR. Discovery of a novel murine keratin 6 (K6) isoform explains the absence of hair and nail defects in mice deficient for K6a and K6b. J Cell Biol. 2001;154:619–30.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Bowden PE, Haley JL, Kansky A, Rothnagel J, Jones DO, Turner RJ. Mutation of a type II keratin gene (K6a) in pachyonychia congenita. Nat Genet. 1995;10:363–5.PubMedCrossRefGoogle Scholar
  152. 152.
    McLean WHI, Rugg EL, Lunny DP, et al. Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet. 1995;9:273–8.PubMedCrossRefGoogle Scholar
  153. 153.
    Wilson NJ, O’Toole EA, Milstone LM, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014;171:343–55.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    van Steensel MA, Jonkman MF, van Geel M, Steijlen PM, McLean WH, Smith FJ. Clouston syndrome can mimic pachyonychia congenita. J Invest Dermatol. 2003;121:1035–8.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Wilson NJ, Hansen CD, Azkur D, et al. Recessive mutations in the gene encoding frizzled 6 cause twenty nail dystrophy – expanding the differential diagnosis for pachyonychia congenita. J Dermatol Sci. 2013;70:58–60.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Baden HP, Lee LD, Kubilus J. A genetic electrophoretic variant of human hair à polypeptides. Am J Hum Genet. 1975;27:472–7.PubMedPubMedCentralGoogle Scholar
  157. 157.
    Mischke D, Wild G. Polymorphic keratins in human epidermis. J Invest Dermatol. 1987;88:191–7.PubMedCrossRefGoogle Scholar
  158. 158.
    Gillespie JM, Marshall RC. Proteins of the hard keratins of echidna, hedgehog, rabbit, ox and man. Aust J Biol Sci. 1977;30:401–9.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Marshall RC. Genetic variation in the proteins of human nail. J Invest Dermatol. 1980;75:264–9.PubMedCrossRefGoogle Scholar
  160. 160.
    Shimomura Y, Aoki N, Rogers MA, Langbein L, Schweizer J, Ito M. Characterization of human keratin-associated protein 1 family members. J Investig Dermatol Symp Proc. 2003;8:96–9.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Hallman JR, Fang D, Setaluri V, White WL. Microtubule associated protein (MAP-2) expression defines the companion layer of the anagen hair follicle and an analogous zone in the nail unit. J Cutan Pathol. 2002;29:549–56.PubMedCrossRefPubMedCentralGoogle Scholar
  162. 162.
    Kalinin AE, Kajava AV, Steinert PM. Epithelial barrier function: assembly and structural features of the cornified cell envelope. BioEssays. 2002;24:789–800.PubMedCrossRefGoogle Scholar
  163. 163.
    Shono S, Toda K. The structure proteins of the human nail. Curr Prob Dermatol. 1983;11:317–26.CrossRefGoogle Scholar
  164. 164.
    Cheng T, van Vlijmen-Willems IM, Hitomi K, et al. Colocalization of cystatin M/E and its target proteases suggests a role in terminal differentiation of human hair follicle and nail. J Invest Dermatol. 2009;129:1232–42.PubMedCrossRefGoogle Scholar
  165. 165.
    Astbury WT, Sisson WA. X-ray studies of the structure of hair, wool, and related fibres. Proc Royal Soc. 1935;150:533–51.CrossRefGoogle Scholar
  166. 166.
    Baden HP. The physical properties of nail. J Invest Dermatol. 1970;55:115–22.PubMedCrossRefGoogle Scholar
  167. 167.
    Derksen JD, Heringa GC, Weidinger A. On keratin and cornification. Acta Neerlandica Morph. 1937;1:31–7.Google Scholar
  168. 168.
    Forslind B, Nordstrom G, Toijer D, Eriksson K. The rigidity of human fingernails: a biophysical investigation on influencing physical parameters. Acta Dermatovener. 1980;60:217–22.Google Scholar
  169. 169.
    Gammeltoft M, Wulf HC. Transmission of 12 kv grenz rays and 29 kv x-rays through normal and diseased nails. Acta Dermatovener. 1980;60:431–62.Google Scholar
  170. 170.
    Kile RL. Some mineral constituents of fingernails. AMA Arch Dermatol Syphil. 1954;70:75–83.CrossRefGoogle Scholar
  171. 171.
    Finlay AY, Frost P, Keith AD, Snipes W. An assessment of factors influencing flexibility of human fingernails. Br J Dermatol. 1980;103:357–65.PubMedCrossRefGoogle Scholar
  172. 172.
    Wessel S, Gniadecka M, Jemec GB, Wulf HC. Hydration of human nails investigated by NIR-FT-Raman spectroscopy. Biochim Biophys Acta. 1999;1433:210–6.PubMedCrossRefGoogle Scholar
  173. 173.
    Walters KA, Abdalghafor HM, Lane ME. The human nail – barrier characterisation and permeation enhancement. Int J Pharm. 2012;435:10–21.PubMedCrossRefGoogle Scholar
  174. 174.
    Burch GE, Winsor T. Diffusion of water through dead plantar palmar and torsal human skin and through toe nails. Arch Dermatol Syphil. 1946;53:39–41.CrossRefGoogle Scholar
  175. 175.
    Spruit D. Measurement of water vapor loss through human nail in vivo. J Invest Dermatol. 1971;56:359–61.PubMedCrossRefGoogle Scholar
  176. 176.
    Spruit D. Effect of nail polish on the hydration of the fingernail. Am Cosmetics Perfumery. 1972;87:57–8.Google Scholar
  177. 177.
    Jacobi O. Die nagel des lebenden menschen und die perspiratio insensibilis. Arch Klin Exp Dermatol. 1962;214:559–72.PubMedCrossRefGoogle Scholar
  178. 178.
    Walters KA, Flynn GL, Marvel JR. Physiocochemical characterization of the human nail: permeation pattern for water and the homologous alcohols and differences with respect to the stratum corneum. J Pharm Pharmacol. 1983;35:28–33.PubMedCrossRefGoogle Scholar
  179. 179.
    Cauwenbergh G, Degreef H, Heykants J, Woestenborghs VRP, Haeverans K. Pharmacokinetic profile of oraly administered itraconazole in human skin. J Am Acad Dermatol. 1988;18:263–8.PubMedCrossRefGoogle Scholar
  180. 180.
    Faergemann J, Zehender H, Denouel J, Millerioux L. Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair, and nails during and after 250 mg terbenafine orally once per day for four weeks. Acta Derm Venereol (Stockh). 1993;73:305–9.Google Scholar
  181. 181.
    Finlay AY. Pharmacokinetics of terbinafine in the nail. Br J Dermatol. 1992;126(Supplement 39):28–32.PubMedCrossRefGoogle Scholar
  182. 182.
    Matthieu L, De Doncker P, Cauwenbergh G, et al. Itraconazole penetrates the nail via the nail matrix and the nail bed – an investigation in onychomycosis. Clin Exp Dermatol. 1991;16:374–6.PubMedCrossRefGoogle Scholar
  183. 183.
    Ceschin-Roques CG, Hanel H, Pruja-Bougaret SM, Luc J, Vandermander J, Michel G. Ciclopirox nail lacquer 8%: in vivo penetration into and through nails and in vitro effect on pig skin. Skin Pharmacol. 1991;4:89–94.PubMedCrossRefGoogle Scholar
  184. 184.
    Hui X, Chan TC, Barbadillo S, Lee C, Maibach HI, Wester RC. Enhanced econazole penetration into human nail by 2-n-nonyl-1,3-dioxolane. J Pharm Sci. 2003;92:142–8.PubMedCrossRefGoogle Scholar
  185. 185.
    Barot BS, Parejiya PB, Patel HK, Mehta DM, Shelat PK. Drug delivery to the nail: therapeutic options and challenges for onychomycosis. Crit Rev Ther Drug Carrier Syst. 2014;31:459–94.PubMedCrossRefGoogle Scholar
  186. 186.
    Zaias N. The embryology of the human nail. Arch Dermatol. 1963;87:39.CrossRefGoogle Scholar
  187. 187.
    Zaias N, Ackerman AB. The nail in Darier-White disease. Arch Dermatol. 1973;107:193.PubMedCrossRefGoogle Scholar
  188. 188.
    Zaias N. Psoriasis of the nail. Arch Dermatol. 1969;99:569.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyUniversity of WashingtonSeattleUSA
  2. 2.Department of DermatologyKaiser PermanenteSeattleUSA

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