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Purification of non-infectious ganglioside preparations from scrapie-infected brain tissue

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Summary

The extraction and purification of gangliosides from brains of animals infected with the scrapie agent was evaluated by scaling-down a large-scale procedure currently used with bovine brains. Inactivation experiments employed hamster brains infected with the 263 K strain of scrapie. Residual infectivity was determined at different points of the procedure and in the final preparation by an in vivo animal bioassay. The efficacy of single steps, which included chemicals or physical techniques known to affect the viability of the scrapie agent, was verified by spiking experiments where known amounts of infectivity were added just before each single step. Infectivity was significantly diminished at early stages of the purification, and no infectivity was detected in the final preparation containing purified gangliosides. The significant reduction of infectivity at intermediate steps and the total absence of detectable infectivity in the final product confirmed that a combination of heat and exposure to sodium hydroxide, even in the presence of organic solvents, completely inactivated the scrapie agent.

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References

  1. Asher DM, Gibbs CJ Jr, Gajdusek DC (1986) Slow viral infections: safe handling of the agents of subacute spongiform encephalopathies. In: Miller BM (ed) Laboratory safety: principles and practices. American Society for Microbiology, Washington, DC, pp 59–71

    Google Scholar 

  2. Brown P (1985) Virus sterility for human growth hormone. Lancet ii: 729–730

    Google Scholar 

  3. Brown P, Cathala F, Raubertas RF, Gajdusek DC, Castaigne P (1987) The epidemiology of Creutzfeldt-Jakob disease: conclusion of a 15-year investigation in France and review of the world literature. Neurology 37: 895–904

    Google Scholar 

  4. Brown P, Gajdusek DC, Gibbs CJ Jr, Asher DM (1985) Potential epidemic of Creutzfeldt-Jakob disease from human growth hormone therapy. N Engl J Med 313: 728–731

    Google Scholar 

  5. Brown P, Rohwer RG, Gajdusek DC (1984) Sodium hydroxide decontamination of Creutzfeldt-Jakob disease virus. N Engl J Med 310: 727

    Google Scholar 

  6. Brown P, Rohwer RG, Gajdusek DC (1986) Newer data on the inactivation of scrapie virus or Creutzfeldt-Jakob disease virus in brain tissue. J Infect Dis 153: 1145–1148

    Google Scholar 

  7. Chigorno V, Sonnino S, Ghidoni R, Tettamanti G (1982) Densitometric quantification of brain gangliosides separated by two-dimensional thin-layer chromatography. Neurochem Int 5: 397–403

    Google Scholar 

  8. Formisano S, Johnson ML, Lee G, Aloj SM, Edelhock H (1979) Critical micelle concentrations of gangliosides. Biochemistry 18: 1119–1124

    Google Scholar 

  9. Gajdusek DC (1990) Subacute spongiform encephalopathies: transmissible cerebral amyloidoses caused by unconventional viruses. In: BN Fields, DM Knipe (eds) Virology, 2nd edn. Raven Press, New York, pp 2289–2324

    Google Scholar 

  10. Geisler FH, Dorsey FC, Coleman WP (1991) Motor recovery following human spinal cord injury. A randomized placebo controlled trial with GM1 ganglioside. N Engl J Med 324: 1829–1838

    Google Scholar 

  11. Hope J, Reekie LJD, Hunter N, Multhaup G, Beyreuther K, White H, Scott AC, Stack MJ, Dawson M, Wells GAH (1988) Fibrils from brain of cows with new cattle disease contain scrapie-associated protein. Nature 336: 390–392

    Google Scholar 

  12. IUPAC-IUB Commission on biochemical nomenclature (1977) The nomenclature of lipids. Eur J Biochem 79: 11–21

    Google Scholar 

  13. Kimberlin RH, Walker CA (1989) Transport, targeting and replication of scrapie in CNS. In: Court LA, Dormont D, Brown P, Kingsbury DT (eds) Unconventional virus diseases of the central nervous system. Commissariat à l'Énergie Atomique, Fontenayaux-Roses, France, pp 547–562

    Google Scholar 

  14. Kimberlin RH, Walker CA, Millson GC, Taylor DM, Robertson PA, Tomlinson AH, Dickinson AG (1983) Disinfection studies with two strain of mouse-passaged scrapie agent. J Neurol Sci 59: 355–369

    Google Scholar 

  15. Masters CL, Harris JO, Gajdusek DC, Gibbs CJ Jr, Bernouilli C, Asher DM (1979) Creutzfeldt-Jakob disease: patterns of world-wide occurrence and the significance of familial and sporadic clustering. Ann Neurol 5: 177–188

    Google Scholar 

  16. Minor P (1990) Bovine spongiform encephalopathy and biological products for human use. Biologicals 18: 77–80

    Google Scholar 

  17. Morgan KL (1988) Bovine spongiform encephalopathy: time to take scrapie seriously. Vet Rec 122: 445–446

    Google Scholar 

  18. Parry HB (1983) Scrapie disease in sheep. Academic Press, London

    Google Scholar 

  19. Pocchiari M, Peano S, Conz A, Eshkol A, Maillard F, Brown P, Gibbs CJ Jr, Xi YG, Tenham-Fisher E, Macchi G (1991) Combination ultrafiltration and 6M urea treatment of human growth hormone minimizes risk from potential CJD contamination. Horm Res 35: 161–166

    Google Scholar 

  20. Prusiner SB (1991) Molecular biology of prion diseases. Science 252: 1515–1522

    Google Scholar 

  21. Prusiner SB, Groth DF, McKinley MP, Cochran SP, Bowman KA, Casper KC (1981) Thiocyanate and hydroxyl ions inactivate the scrapie agent. Proc Natl Acad Sci USA 78: 4606–4610

    Google Scholar 

  22. Reed LJ, Muench H (1938) A simple method of estimating fifty per cent endpoints. Am J Hyg 27: 493–497

    Google Scholar 

  23. Rosenberg RN, White CL, Brown P, Gajdusek DC, Volpe JJ, Posner J, Dyck PJ (1986) Precautions in handling tissues, fluids, and other contaminated material from patients with documented or suspected Creuzfeldt-Jakob disease. Ann Neurol 19: 75–77

    Google Scholar 

  24. Sabel BA, Stein DG (1986) Pharmacological treatment of central nervous system injury. Nature 323: 493

    Google Scholar 

  25. Safar J, Ceroni M, Piccardo P, Gajdusek DC, Gibbs CJ Jr (1990) Scrapie-associated precursor proteins: antigenic relationship between species and immunochemical localization in normal, scrapie and Creutzfeldt-Jakob disease brains. Neurology 40: 513–517

    Google Scholar 

  26. Safar J, Ceroni M, Piccardo P, Liberski PP, Miyazaki M, Gajdusek DC, Gibbs CJ Jr (1990) Subcellular distribution and physicochemical properties of scrapie-associated precursor protein and relationship with the scrapie agent. Neurology 40: 503–508

    Google Scholar 

  27. Svennerholm L, Fredman P (1980) A procedure for the quantitative isolation of brain gangliosides. Biochim Biophys Acta 617: 97–109

    Google Scholar 

  28. Tamai Y, Taguchi F, Miura S (1988) Inactivation of the Creutzfeldt-Jakob disease agent. Ann Neurol 24: 466–467

    Google Scholar 

  29. Tateishi J, Tashima T, Kitamoto T (1988) Inactivation of the Creutzfeldt-Jakob disease agent. Ann Neurol 24: 466

    Google Scholar 

  30. Walker AS, Inderlied CB, Kingsbury DT (1983) Conditions for the chemical and physical inactivation of the K.Fu. strain of the agent of Creutzfeldt-Jakob disease. Am J Public Health 73: 661–665

    Google Scholar 

  31. Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R (1987) A novel progressive spongiform encephalopathy in cattle. Vet Rec 121: 419–420

    Google Scholar 

  32. Wiegandt H (1985) Gangliosides. In: Wiegandt H (ed) Glycolipids. Elsevier, Amsterdam, pp 199–260 (New comprehensive biochemistry, vol 10)

    Google Scholar 

  33. Wilesmith JW (1990) Epidemiology and current status of bovine spongiform encephalopathy in the United Kingdom. J Am Vet Med Assoc 196: 1674–1675

    Google Scholar 

  34. Yu RK, Saito M (1989) Structure and localization of gangliosides. In: Margolis RU, Margolis RK (eds) Neurobiology of glycoconjugates. Plenum, New York, pp 1–42

    Google Scholar 

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Author notes

  1. M. Ceroni

    Present address: Fondazione Istituto Neurologico “Casimiro Mondino”, Pavia, Italy

Authors and Affiliations

  1. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

    A. Di Martino, J. Safar, M. Ceroni & C. J. Gibbs Jr.

Authors
  1. A. Di Martino
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  2. J. Safar
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  3. M. Ceroni
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  4. C. J. Gibbs Jr.
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Di Martino, A., Safar, J., Ceroni, M. et al. Purification of non-infectious ganglioside preparations from scrapie-infected brain tissue. Archives of Virology 124, 111–121 (1992). https://doi.org/10.1007/BF01314629

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  • DOI: https://doi.org/10.1007/BF01314629

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