New Molecular and Innovations in Forensic Pathology

  • Toshikazu Kondo
  • Yuko Ishida
  • Akihiko Kimura
  • Mizuho Nosaka
Chapter

Abstract

In forensic pathology, the novel molecular biomarkers as well as innovative devices and techniques are always explored for the correct diagnosis of the cause of death, postmortem intervals, wound ages, and so on. In wound age determination, application techniques, and target cells and molecules are main elements. Bone marrow-derived cells such as fibrocytes and endothelial progenitor cells can contribute to skin wound healing, thus implying that those cells would be candidate cells for wound age determination. Analyses of aquaporins that are water channels in mammals would be helpful for the differential diagnosis of saltwater and freshwater drowning. Circadian rhythm is well controlled by the time-dependent expression of “clock genes”, indicating that analyses of the biological clock would be powerful methods for the estimation of the time of death. Postmortem computed tomography (PMCT) has rapidly and widely spread, and assists forensic autopsy. Actually, it is unnecessary to mention that the advancement of molecular and imaging innovations is able to contribute to the progress of forensic pathology.

References

  1. 1.
    Jeffreys AJ, Wilson V, Thein SL (1985) Individual-specific ‘fingerprints’ of human DNA. Nature 316(6023):76–79CrossRefPubMedGoogle Scholar
  2. 2.
    Kondo T, Ishida Y (2010) Molecular pathology of wound healing. Forensic Sci Int 203(1–3):93–98CrossRefPubMedGoogle Scholar
  3. 3.
    Kondo T (2007) Timing of skin wounds. Leg Med (Tokyo) 9(2):109–114CrossRefGoogle Scholar
  4. 4.
    Nosaka M, Ishida Y, Kimura A, Hama M, Kawaguchi T, Yamamoto H, Kuninaka Y, Shimada E, Kondo T (2015) Immunohistochemical detection of intrathrombotic IL-6 and its application to thrombus age estimation. Int J Legal Med 129(5):1021–1025CrossRefPubMedGoogle Scholar
  5. 5.
    Nosaka M, Ishida Y, Kimura A, Kondo T (2013) Immunohistochemical detection of intrathrombotic macrophage-derived cytokines and its application to thrombus age estimation in murine deep vein thrombosis model. Int J Legal Med 127(5):937–942CrossRefPubMedGoogle Scholar
  6. 6.
    Nosaka M, Ishida Y, Kimura A, Kondo T (2010) Immunohistochemical detection of MMP-2 and MMP-9 in a stasis-induced deep vein thrombosis model and its application to thrombus age estimation. Int J Legal Med 124(5):439–444CrossRefPubMedGoogle Scholar
  7. 7.
    Hayashi T, Ishida Y, Mizunuma S, Kimura A, Kondo T (2009) Differential diagnosis between freshwater drowning and saltwater drowning based on intrapulmonary aquaporin-5 expression. Int J Legal Med 123(1):7–13CrossRefPubMedGoogle Scholar
  8. 8.
    An JL, Ishida Y, Kimura A, Kondo T (2011) Immunohistochemical examination of intracerebral aquaporin-4 expression and its application for differential diagnosis between freshwater and saltwater drowning. Int J Legal Med 125(1):59–65CrossRefPubMedGoogle Scholar
  9. 9.
    An JL, Ishida Y, Kimura A, Kondo T (2010) Forensic application of intrarenal aquaporin-2 expression for differential diagnosis between freshwater and saltwater drowning. Int J Legal Med 124(2):99–104CrossRefPubMedGoogle Scholar
  10. 10.
    Maeda H, Ishikawa T, Michiue T (2014) Forensic molecular pathology: its impacts on routine work, education and training. Leg Med (Tokyo) 16(2):61–69CrossRefGoogle Scholar
  11. 11.
    Maeda H, Ishikawa T, Michiue T (2011) Forensic biochemistry for functional investigation of death: concept and practical application. Leg Med (Tokyo) 13(2):55–67CrossRefGoogle Scholar
  12. 12.
    Walcher K (1930) Über vitale Reaktionen. Dtsch Z ges gerichtl Med 15:16–57Google Scholar
  13. 13.
    Orsos F (1935) Die vitalen Reaktionen und ihre gerichtsmedizinische Bedeutung. Beitr Pathol Anat 95:163–241Google Scholar
  14. 14.
    Raekallio J (1976) Timing of wounds in forensic medicine. Jpn J Legal Med 30:125–136Google Scholar
  15. 15.
    Berg S, Ditt J, Friedrich D, Bonte W (1968) Mo¨glichkeiten der biochemischen Wundaltersbestimmung. Dtsch Z Gerichtl Med 63:183–198Google Scholar
  16. 16.
    Berg S, Bonte W (1971) Praktische Erfahrungen mit der biochemischen Wundaltersbestimmung. Beitr Gerichtl Med 28:108–114Google Scholar
  17. 17.
    Grose R, Werner S (2004) Wound-healing studies in transgenic and knockout mice. Mol Biotechnol 28:147–166CrossRefPubMedGoogle Scholar
  18. 18.
    Lin ZQ, Kondo T, Ishida Y, Takayasu T, Mukaida N (2003) Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice. J Leukoc Biol 73(6):713–721CrossRefPubMedGoogle Scholar
  19. 19.
    Ishida Y, Kondo T, Kimura A, Matsushima K, Mukaida N (2006) Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF-κB activation and a reciprocal suppression of TGF-β signal pathway. J Immunol 176(9):5598–5606CrossRefPubMedGoogle Scholar
  20. 20.
    Mori R, Kondo T, Ohshima T, Ishida Y, Mukaida N (2002) Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration. FASEB J 16(9):963–974CrossRefPubMedGoogle Scholar
  21. 21.
    Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N (2004) The essential involvement of cross-talk between IFN-γ and TGF-β in the skin wound-healing process. J Immunol 172(3):1848–1855CrossRefPubMedGoogle Scholar
  22. 22.
    Ishida Y, Gao JL, Murphy PM (2008) Chemokine receptor CX3CR1 mediates skin wound healing by promoting macrophage and fibroblast accumulation and function. J Immunol 180(1):569–579CrossRefPubMedGoogle Scholar
  23. 23.
    Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. Int J Legal Med 108(5):231–236CrossRefPubMedGoogle Scholar
  24. 24.
    Kondo T, Ohshima T, Eisenmenger W (1999) Immunohistochemical and morphometrical study on the temporal expression of interleukin-1α (IL-1α) in human skin wounds for forensic wound age determination. Int J Legal Med 112(4):249–252CrossRefPubMedGoogle Scholar
  25. 25.
    Grellner W (2002) Time-dependent immunohistochemical detection of proinflammator cytokines (IL-1β, IL-6, TNF-α) in human skin wounds. Forensic Sci Int 130:90–96CrossRefPubMedGoogle Scholar
  26. 26.
    Mukaida N, Harada A, Matsushima K (1998) Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine Growth Factor Rev 9(1):9–23CrossRefPubMedGoogle Scholar
  27. 27.
    Kondo T, Ohshima T, Mori R, Guan DW, Ohshima K, Eisenmenger W (2002) Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination. Int J Legal Med 116(2):87–91CrossRefPubMedGoogle Scholar
  28. 28.
    Sasaki M, Abe R, Fujita Y, Ando S, Inokuma D, Shimizu H (2008) Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type. J Immunol 180:2581–2587CrossRefPubMedGoogle Scholar
  29. 29.
    Wada T, Sakai N, Sakai Y, Matsushima K, Kaneko S, Furuichi K (2011) Involvement of bone-marrow-derived cells in kidney fibrosis. Clin Exp Nephrol 15(1):8–13CrossRefPubMedGoogle Scholar
  30. 30.
    Ishida Y, Kimura A, Kondo T, Hayashi T, Ueno M, Takakura N, Matsushima K, Mukaida N (2007) Essential roles of the CC chemokine ligand 3-CC chemokine receptor 5 axis in bleomycin-induced pulmonary fibrosis through regulation of macrophage and fibrocyte infiltration. Am J Pathol 170:843–854CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1(1):71–81PubMedPubMedCentralGoogle Scholar
  32. 32.
    Ishida Y, Kimura A, Takayasu T, Eisenmenger W, Kondo T (2009) Detection of fibrocytes in human skin wounds and its application for wound age determination. Int J Legal Med 123(4):299–304CrossRefPubMedGoogle Scholar
  33. 33.
    Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967CrossRefPubMedGoogle Scholar
  34. 34.
    Murasawa S, Asahara T (2005) Endothelial progenitor cells for vasculogenesis. Physiology (Bethesda) 20:36–42Google Scholar
  35. 35.
    Ishida Y, Kimura A, Kuninaka Y, Inui M, Matsushima K, Mukaida N, Kondo T (2012) Pivotal role of the CCL5/CCR5 interaction for recruitment of endothelial progenitor cells in mouse wound healing. J Clin Invest 122(2):711–721CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ishida Y, Kimura A, Nosaka M, Kuninaka Y, Shimada E, Yamamoto H, Nishiyama K, Inaka S, Takayasu T, Eisenmenger W, Kondo T (2015) Detection of endothelial progenitor cells in human skin wounds and its application for wound age determination. Int J Legal Med 129(5):1049–1054CrossRefPubMedGoogle Scholar
  37. 37.
    Combadiere C, Ahuja SK, Tiffany HL, Murphy PM (1996) Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1α, MIP-1β, and RANTES. J Leukoc Biol 60(1):147–152CrossRefPubMedGoogle Scholar
  38. 38.
    Wong MM, Fish EN (2003) Chemokines: attractive mediators of the immune response. Semin Immunol 15(1):5–14CrossRefPubMedGoogle Scholar
  39. 39.
    Grellner W, Madea B (2007) Demands on scientific studies: vitality of wounds and wound age estimation. Forensic Sci Int 165:150–154CrossRefPubMedGoogle Scholar
  40. 40.
    Bonelli A, Bacci S, Vannelli B, Norelli A (2003) Immunohistochemical localization of mast cells as a tool for the discrimination of vital and postmortem lesions. Int J Legal Med 117:14–18CrossRefPubMedGoogle Scholar
  41. 41.
    Gauchotte G, Wissler MP, Casse JM, Pujo J, Minetti C, Gisquet H, Vigouroux C, Plenat F, Vignaud JM, Martrille L (2013) FVIIIra, CD15, and tryptase performance in the diagnosis of skin stab wound vitality in forensic pathology. Int J Legal Med 127:957–965CrossRefPubMedGoogle Scholar
  42. 42.
    Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741CrossRefPubMedGoogle Scholar
  43. 43.
    Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 3:542–545CrossRefPubMedGoogle Scholar
  44. 44.
    Kimura A, Ishida Y, Wada T, Hisaoka T, Morikawa Y, Sugaya T, Mukaida N, Kondo T (2010) The absence of interleukin-6 enhanced arsenite-induced renal injury by promoting autophagy of tubular epithelial cells with aberrant extracellular signal-regulated kinase activation. Am J Pathol 176:40–50CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kimura A, Ishida Y, Inagaki M, Nakamura Y, Sanke T, Mukaida N, Kondo T (2012) Interferon-gamma is protective in cisplatin-induced renal injury by enhancing autophagic flux. Kidney Int 82:1093–1104CrossRefPubMedGoogle Scholar
  46. 46.
    Kimura A, Ishida Y, Nosaka M, Shiraki M, Hama M, Kawaguchi T, Kuninaka Y, Shimada E, Yamamoto H, Takayasu T, Kondo T (2015) Autophagy in skin wounds: a novel marker for vital reactions. Int J Legal Med 129(3):537–541CrossRefPubMedGoogle Scholar
  47. 47.
    Saukko P, Knight B (eds) (2004) Knight’s forensic pathology. Arnold, London, pp 395–411Google Scholar
  48. 48.
    Brinkmann B (2004) Tod im Wasser. In: Brinkmann B, Madea B (eds) Handbuch gerichtliche Medizin. Springer, Berlin, Heidelberg, pp 797–818Google Scholar
  49. 49.
    Morild I (1995) Pleural effusion in drowning. Am J Forensic Med Pathol 16:253–256CrossRefPubMedGoogle Scholar
  50. 50.
    Zhu BL, Quan L, Li DR, Taniguchi M, Kamikodai Y, Tsuda K, Fujita MQ, Tsuji T, Maeda H (2003) Postmortem lung weight in drowning: a comparison with acute asphyxiation and cardiac death. Legal Med 5:20–26CrossRefPubMedGoogle Scholar
  51. 51.
    Reidbord HE, Spitz WU (1966) Ultrastructural alterations in rat lungs. Changes after intratracheal perfusion with freshwater and seawater. Arch Pathol 81:103–111PubMedGoogle Scholar
  52. 52.
    Brinkmann B, Fechner G, Püschel K (1983) Zur Ultrastrukturpathologie des Alveolarapparates beim experimentellen Ertrinken. Z Rechtsmed 91:47–60CrossRefPubMedGoogle Scholar
  53. 53.
    Nopanitaya W, Gambill TG, Brinkhous KM (1974) Fresh water drowning. Pulmonary ultrastructure and systemic fibrinolysis. Arch Pathol 98:361–366PubMedGoogle Scholar
  54. 54.
    Swann HG, Spafford NR (1951) Body salt and water changes during fresh and sea water drowning. Tex Rep Biol Med 9:356–382PubMedGoogle Scholar
  55. 55.
    Azparren JE, Vallejo G, Reyes E, Herranz A, Snacho M (1998) Study of the diagnostic value of strontium, chloride, haemoglobin and diatoms in immersion cases. Forensic Sci Int 91:123–132CrossRefPubMedGoogle Scholar
  56. 56.
    Lorente JA, Villanueva E, Hernández-Cueto C, Luna JD (1990) Plasmatic levels of atrial natriuretic peptide (ANP) in drowning. A pilot study. Forensic Sci Int 44:69–75CrossRefPubMedGoogle Scholar
  57. 57.
    Grandmaison GL, Leterreux M, Lasseuguette K, Alvarez JC, Mazancourt P, Durigon M (2006) Study of the diagnostic value of iron in fresh water drowning. Forensic Sci Int 157:117–120CrossRefPubMedGoogle Scholar
  58. 58.
    Azparren JE, Perucha E, Martinez P, Munoz R, Vallejo G (2006) Factors affecting strontium absorption in drownings. Forensic Sci Int 168:138–142CrossRefPubMedGoogle Scholar
  59. 59.
    Verkman AS, Michael A, Matthay MA, Song Y (2000) Aquaporin water channels and lung physiology. Am J Physiol Cell Mol Physiol 278:867–879CrossRefGoogle Scholar
  60. 60.
    Verkman AS (2002) Aquaporin water channels and endothelial cell function. J Anat 200:617–627CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Verkman AS (2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118:3225–3232CrossRefPubMedGoogle Scholar
  62. 62.
    Gunnarson E, Zelenina M, Aperia A (2004) Regulation of brain quaporins. Neuroscience 129:947–955CrossRefPubMedGoogle Scholar
  63. 63.
    Satoh J, Tabunoki H, Yamamura T, Arima K, Konno H (2007) Uman astrocytes express aquaporin-1 and aquaporin-4 in vitro nd in vivo. Neuropathology 27:245–256CrossRefPubMedGoogle Scholar
  64. 64.
    Misawa T, Arima K, Mizusawa H, Satoh J (2008) Close ssociation of water channel AQP1 with amyloid-beta deposition n Alzheimer disease brains. Acta Neuropathol 116:247–260CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Manley GT, Fujimura M, Ma T, Noshita N, Filiz F, Bollen AW, Chan P, Verkman AS (2000) Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med 6:159–163CrossRefPubMedGoogle Scholar
  66. 66.
    Papadopoulos MC, Manley GT, Krishna S, Verkman AS (2004) Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema. FASEB J 18:1291–1293CrossRefPubMedGoogle Scholar
  67. 67.
    Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA (2002) Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205–244CrossRefPubMedGoogle Scholar
  68. 68.
    Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–320CrossRefPubMedGoogle Scholar
  69. 69.
    Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417:78–83CrossRefPubMedGoogle Scholar
  70. 70.
    Yoo SH, Yamazaki S, Lowrey PL, Shimomura K, Ko CH, Buhr ED, Siepka SM, Hong HK, Oh WJ, Yoo OJ, Menaker M, Takahashi JS (2004) PERIOD2:LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A 101:5339–5346CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Helfrich-Förster C, Edwards T, Yasuyama K, Wisotzki B, Schneuwly S, Stanewsky R, Meinertzhagen IA, Hofbauer A (2002) The extraretinal eyelet of Drosophila: development, ultrastructure, and putative circadian function. J Neurosci 22:9255–9266PubMedGoogle Scholar
  72. 72.
    Ko CH, Takahashi JS (2006) Molecular components of the mammalian circadian clock. Hum Mol Genet 15:R271–R277CrossRefPubMedGoogle Scholar
  73. 73.
    DeBruyne JP, Weaver DR, Reppert SM (2007) CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10:543–545CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kimura A, Ishida Y, Hayashi T, Nosaka M, Kondo T (2010) Estimating time of death based on the biological clock. Int J Legal Med 125(3):385–391CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2017

Authors and Affiliations

  • Toshikazu Kondo
    • 1
  • Yuko Ishida
    • 1
  • Akihiko Kimura
    • 1
  • Mizuho Nosaka
    • 1
  1. 1.Department of Forensic MedicineWakayama Medical UniversityWakayamaJapan

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