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Forensic application of VEGF expression to skin wound age determination

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Abstract

An immunohistochemical study combined with morphometry was carried out to examine the time-dependent expression of vascular endothelial growth factor (VEGF) using 53 human skin wounds with different wound ages (groups I: 0–12 h, II: 1–4 days, III: 7–14 days and IV: 17–21 days). In the human wound specimens aged 4–12 h, neutrophils recruited at the wound showed no positive signals for VEGF. With an increase in wound ages of ≥7 days, granulation tissue and angiogenesis were observed, with the migration of macrophages and fibroblasts of which the cytoplasm expressed VEGF-positive reactions. Morphometrically, the average VEGF-positive ratio was highest in group III, followed by that of group IV. In groups III and IV, 13 out of 26 wound samples had VEGF-positive ratios of more than 50%. However, all of the wound samples in groups I and II showed VEGF-positive ratios of less than 50%. With regard to the practical applicability and forensic validity, these observations suggest that a VEGF-positive ratio of more than 50% possibly indicates a wound age of 7 days or more.

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References

  1. Martin P (1997) Wound healing—aiming for perfect skin regeneration. Science 276:75–81

    Article  CAS  PubMed  Google Scholar 

  2. Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746

    Article  CAS  PubMed  Google Scholar 

  3. Raekallio J (1972) Determination of the age of wounds by histochemical and biochemical methods. Forensic Sci Int 1:3–16

    Article  CAS  Google Scholar 

  4. Laiho K (1998) Myeloperoxidase activity in skin lesions. I. Influence of the loss of blood, depth of excoriation and thickness of the skin. Int J Legal Med 111:6–9

    Article  CAS  PubMed  Google Scholar 

  5. Laiho K (1998) Myeloperoxidase activity in skin lesions. II. Influence of alcohol and some medicines. Int J Legal Med 111:10–12

    Article  CAS  PubMed  Google Scholar 

  6. Eisenmenger W, Nerlich A, Glück G (1988) Die Bedeutung des Kollagens bei Wundaltersbestimmung. Z Rechtsmed 100:79–100

    CAS  PubMed  Google Scholar 

  7. Oehmichen M (1990) Die Wundheilung. Springer, Berlin Heidelberg New York, pp 5–67

  8. Oehmichen M, Cröpelin A (1995) Temporal course of intravital and postmortem proliferation of epidermal cells after injury—an immunohistochemical study using bromodeoxyuridine in rats. Int J Legal Med 107:257–262

    CAS  PubMed  Google Scholar 

  9. Betz P (1994) Histological and enzyme histochemical parameters for the age estimation of human skin wounds. Int J Legal Med 107:60–68

    CAS  PubMed  Google Scholar 

  10. Dressler J, Busuttil A, Koch R, Harrison DJ (2001) Sequence of melanocyte migration into human scar tissue. Int J Legal Med 115:61–63

    Article  CAS  PubMed  Google Scholar 

  11. Betz P, Nerlich A, Wilske J, Tübel J, Wiest I, Penning R, Eisenmenger W (1992) Immunohistochemical localization of fibronectin as a tool for the age determination of human skin wounds. Int J Legal Med 105:21–26

    CAS  PubMed  Google Scholar 

  12. Betz P, Nerlich A, Wilske J, Tübel J, Penning R, Eisenmenger W (1993) Analysis of the immunohistochemical localization of collagen type III and V for the time-estimation of human skin wounds. Int J Legal Med 105:329–332

    CAS  PubMed  Google Scholar 

  13. Betz P, Nerlich A, Wilske J, Tübel J, Penning R, Eisenmenger W (1993) Immunohistochemical localization of collagen types I and VI in human skin wounds. Int J Legal Med 106:31–34

    CAS  PubMed  Google Scholar 

  14. Betz P (1994) Histological and enzyme histochemical parameters for the age estimation of human skin wounds. Int J Legal Med 107:60–68

    CAS  PubMed  Google Scholar 

  15. Betz P, Nerlich A, Tübel J, Wiest I, Hausmann R (1997) Detection of cell death in human skin wounds of various ages by an in situ end labeling of nuclear DNA fragments. Int J Legal Med 110:240–243

    Article  CAS  PubMed  Google Scholar 

  16. Dreßler J, Bachmann L, Kasper M, Hauck JG, Müller E (1997) Time dependence of the expression ICAM (CD-54) in human skin wound. Int J Legal Med 110:299–304

    Article  PubMed  Google Scholar 

  17. Dreßler J, Bachmann L, Koch R, Müller E (1998) Enhanced expression of selectins in human skin wounds. Int J Legal Med112:39–44

    Google Scholar 

  18. Dreßler J, Bachmann L, Koch R, Müller E (1999) Estimation of wound age and VCAM-1 in human skin. Int J Legal Med 112:159–162

    Article  PubMed  Google Scholar 

  19. Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process mouse skin wound: a preliminary study for possible wound age determination. Int J Legal Med 108:231–236

    CAS  PubMed  Google Scholar 

  20. 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 112:249–252

    Article  CAS  PubMed  Google Scholar 

  21. 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 116:87–91

    Article  CAS  PubMed  Google Scholar 

  22. Ohshima T, Sato Y (1998) Time-dependent expression of interleukin-10 (IL-10) mRNA during the early phase of skin wound healing as possible indicator of wound vitality. Int J Legal Med 111:251–255

    Article  CAS  PubMed  Google Scholar 

  23. Guan D, Ohshima T, Kondo T (2000) Immunohistochemical study on Fas and Fas ligand in skin wound healing. Histochem J 32:85–91

    Article  CAS  PubMed  Google Scholar 

  24. Sato Y, Ohshima T (2000) The expression of mRNA by proinflammatory cytokines during skin wound healing in mice: a preliminary study for forensic wound age estimation (II). Int J Legal Med 113:140–145

    Article  CAS  PubMed  Google Scholar 

  25. Rebolledo Godoy M, Rebolledo Godoy AP, Oehmichen M (2000) AgNORs during the process of wound healing. Time dependency as evaluated in vital and postmortem biopsy. Int J Legal Med 113:244–246

    Article  PubMed  Google Scholar 

  26. Kondo T, Tanaka J, Ishida Y, Mori R, Takayasu T, Ohshima T (2002) Ubiquitin expression in skin wounds and its application to forensic wound age determination. Int J Legal Med 116:267–272

    Article  CAS  PubMed  Google Scholar 

  27. Hausmann R, Betz P (2001) Course of glial immunoreactivity for vimentin, tenascin and alpha1-antichymotrypsin after traumatic injury to human brain. Int J Legal Med 114:338–342

    Article  CAS  PubMed  Google Scholar 

  28. Hausmann R, Betz P (2000) The time course of the vascular response to human brain injury—an immunohistochemical study. Int J Legal Med 113:288–292

    Article  CAS  PubMed  Google Scholar 

  29. Hausmann R, Riess R, Fieguth A, Betz P (2000) Immunohistochemical investigations on the course of astroglial GFAP expression following human brain injury. Int J Legal Med 113:70–75

    Article  CAS  PubMed  Google Scholar 

  30. Hausmann R, Kaiser A, Lang C, Bohnert M, Betz P (1999) A quantitative immunohistochemical study on the time-dependent course of acute inflammatory cellular response to human brain injury. Int J Legal Med 112:227–232

    Article  CAS  PubMed  Google Scholar 

  31. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309

    CAS  PubMed  Google Scholar 

  32. Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858

    CAS  PubMed  Google Scholar 

  33. Burke B, Giannoudis A, Corke KP, Gill D, Wells M, Ziegler-Heitbrock L, Lewis CE (2003) Hypoxia-induced gene expression in human macrophages: implications for ischemic tissues and hypoxia-regulated gene therapy. Am J Pathol 163:1233–1243

    CAS  PubMed  Google Scholar 

  34. Ishida Y, Kondo T, Takayasu T, Iwakura Y, Mukaida N (2004) The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process. J Immunol 172:1848–1855

    CAS  PubMed  Google Scholar 

  35. 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 73:713–721

    Article  CAS  PubMed  Google Scholar 

  36. 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 16:963–974

    Article  CAS  PubMed  Google Scholar 

  37. Ishida Y, Kondo T, Tsuneyama K, Lu P, Takayasu T, Mukaida N (2004) The pathogenic roles of tumor necrosis factor receptor p55 in acetaminophen-induced liver injury in mice. J Leukoc Biol 75:59–67

    Article  CAS  PubMed  Google Scholar 

  38. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z (1999) Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13:9–22

    CAS  PubMed  Google Scholar 

  39. Ozawa K, Kondo T, Hori O, Kitao Y, Stern DM, Eisenmenger W, Ogawa S, Ohshima T (2001) Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport. J Clin Invest 108:41–50

    Article  CAS  PubMed  Google Scholar 

  40. Hausmann R, Nerlich A, Betz P (1998) The time-related expression of p53 protein in human skin wounds—a quantitative immunohistochemical analysis. Int J Legal Med 111:169–172

    Article  CAS  PubMed  Google Scholar 

  41. Betz P, Nerlich A, Wilske J, Tübel J, Penning R, Eisenmenger W (1992) Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds. Int J Legal Med 105:99–103

    CAS  PubMed  Google Scholar 

  42. Takamiya M, Saigusa K, Aoki Y (2002) Immunohistochemical study of basic fibroblast growth factor and vascular endothelial growth factor expression for age determination of cutaneous wounds. Am J Forensic Med Pathol 23:264–267

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was financially supported by Grants-in-Aid for Encouragement of Young Scientists from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

  1. Department of Forensic Medicine, Wakayama Medical University, 811–1 Kmiidera, 641–8509, Wakayama, Japan

    Takahito Hayashi, Yuko Ishida, Akihiko Kimura & Toshikazu Kondo

  2. Department of Forensic and Social Environmental Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, 920-8640, Kanazawa, Japan

    Tatsunori Takayasu

  3. Institute for Legal Medicine, University of Munich, Frauenlobstrasse 7a, 80337, Munich, Germany

    Wolfgang Eisenmenger

Authors
  1. Takahito Hayashi
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  2. Yuko Ishida
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  3. Akihiko Kimura
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  4. Tatsunori Takayasu
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  5. Wolfgang Eisenmenger
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  6. Toshikazu Kondo
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Correspondence to Toshikazu Kondo.

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Hayashi, T., Ishida, Y., Kimura, A. et al. Forensic application of VEGF expression to skin wound age determination. Int J Legal Med 118, 320–325 (2004). https://doi.org/10.1007/s00414-004-0468-x

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  • DOI: https://doi.org/10.1007/s00414-004-0468-x

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