Deutsche Zeitschrift für Nervenheilkunde

, Volume 192, Issue 3, pp 265–274 | Cite as

The significance of astroglial hypertrophy in Scrapie, Kuru, Multiple Sclerosis and old age together with a note on the possible nature of the scrapie agent

  • E. J. Field
Article

Summary

Attention is drawn to certain resemblances between some of the pathological features of scrapie, kuru, multiple sclerosis and old age. It is suggested that there may be a common factor in these changes, that it is the hypertrophic change in glial cells, and that this resembles benign neoplasia. It is suggested that these changes are associated with aggregation of polysaccharide chains within the cytoplasm and that these foci “seed out” the further formation and aggregation of polysaccharide by the cell so that its metabolism is ultimately quite disturbed. Aggregates of polysaccharide chains may themselves act as further seeding foci so that an illusion of a self replicating agent may result.

Zusammenfassung

Auf gewisse pathomorphologische Ähnlichkeiten zwischen Scrapie, Kuru, Multiple Sklerose und Altersdegeneration wird hingewiesen. Ein gemeinsamer Faktor in diesen Veränderungen wird vermutet, bei dem es sich um hypertrophische Vorgänge in Gliazellen, ähnlich einer gutartigen Neoplasie, handelt. Diese Veränderungen könnten mit einer Aggregation von Polysaccharidketten im Cytoplasma in Beziehung stehen. Derartige Polysaccharidaggregate könnten als Foci einer weiteren Aggregation wirken und einen Vorgang auslösen, durch welchen der Zellstoffwechsel tiefgreifend beeinträchtigt wird. Solche Aggregate von Polysaccharidketten könnten hinwiederum als sekundäre Foci wirken, so daß die Illusion eines sich selbst reduplizierenden Agens resultiert.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams, D. H., and E. A. Caspary: Nature of the scrapie virus. Brit. med. J. 1967 III, 173.Google Scholar
  2. Allfrey, V. G., R. Faulkner, and A. E. Mirsky: Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. nat. Acad. Sci. (Wash.) 51, 786 (1964).Google Scholar
  3. Alper, T., W. A. Cramp, D. A. Haig, and M. C. Clarke: Does the agent of scrapie replicate without nucleic acid? Nature (Lond.) 214, 764 (1967).Google Scholar
  4. D. A. Haig, and M. C. Clarke: The exceptionally small size of the scrapie agent. Biochem. biophys. Res. Commun. 22, 278 (1966).Google Scholar
  5. Anton, G., u. Fr. Wohlwill: Multiple nicht eitrige Encephalomyelitis und Multiple Sklerose. Z. ges. Psychiat. 12, 31 (1912).Google Scholar
  6. Beck, E., and P. M. Daniel: Kura and scrapie compared: are they examples of system degeneration. NINDB Monograph No. 2. Slow, latent and temperate virus infections. Ed. D. C. Gajdusek, C. J. Gibbs, and M. Alpers. 85 (1965).Google Scholar
  7. Bennet, W. S., G. Eglinton, and S. Kovac: Self association of phenolics and of bile acid derivatives. Nature (Lond.) 214, 776 (1967).Google Scholar
  8. Caspary, E. A., and F. Sewell: Unpublished work (1967).Google Scholar
  9. Chandler, R. L.: Encephalopathy in mice produced with scrapie brain material. Lancet 1961 I, 1378.Google Scholar
  10. Role of electron microscopy in research in scrapie. Proc. roy. Mic. Soc. 1, 118 (1966).Google Scholar
  11. Cytopathology of scrapie in the rat: An electron microscopic study of thalamic and hippocampal areas. Res. Vet. Sci. 8, 98 (1967).Google Scholar
  12. Electron microscopic and other observations on the ependyma and small cerebral blood vessels in mice and rats affected with scrapie. Res. Vet. Sci. 8, 166 (1967).Google Scholar
  13. and J. Fisher: Experimental transmission of scrapie to rats. Lancet 1963 II, 1165.Google Scholar
  14. Charcot, J. M.: Histologie de la sclerose en plaques. Gaz. Hop., Paris 41, 554, 557, 566 (1868).Google Scholar
  15. Maladies du systeme nerveux pp. 239–240. Paris: Delahaye 1872.Google Scholar
  16. Leçons sur les maladies du systeme nerveux. Paris: Delahaye et Lecrosnier 1880.Google Scholar
  17. Defendi, V., and F. Jensen: Oncogenicity by DNA tumor viruses: enhancement after ultraviolet and cobalt-60 radiations. Science 157, 703 (1967).Google Scholar
  18. Dische, Z.: Quoted by Robbins et al. (1966).Google Scholar
  19. Duncan, D., and V. Williams: On the occurrence of a precise order in axoplasm. Tex. Rep. Biol. Med. 20, 503 (1962).Google Scholar
  20. Ferraro, A.: Ageing changes in N. S. In American Handbook of Psychiatry. Ed. S. Arieti. New York: Basic Books 1959.Google Scholar
  21. Field, E. J.: Transmission experiments with multiple sclerosis: An interim report. Brit. Med. J. 1966 II, 564.Google Scholar
  22. H. Miller, D. S. Russell: Observations on glial inclusion bodies in a case of acute disseminated sclerosis. J. clin. Path. 15, 278 (1962).Google Scholar
  23. -- and C. S. Raine: Electron microscope examination of scrapie mouse brain. Third European Regional Conference on Electron Microscopy 293 (1964).Google Scholar
  24. An electron microscopic study of scrapie in the mouse. Acta neuropath. (Berl.) 4, 200 (1964).Google Scholar
  25. Observations on dense body structure in nerve cells with special reference to scrapie. Res. Vet. Sci. 7, 292 (1966).Google Scholar
  26. -- -- Lattice fibrillar or herringbone structures in kuru. Vet. Rec. (in press 1967).Google Scholar
  27. and G. Joyce: Scrapie in the rat: An electron microscope study. 1. Amyloid bodies and deposits. Acta Neuropath. (Berl.) 8, 47 (1967).Google Scholar
  28. -- -- -- Scrapie in the rat: An electron microscope study. II. Glial inclusions. Acta Neuropath. (Berl.) (in press 1967).Google Scholar
  29. and G. D. Windsor: Cultural characters of scrapie mouse brain. Res. Vet. Sci. 6, 130 (1965).Google Scholar
  30. Gajdusek, D. C., C. J. Gibbs, and M. Alpers: Transmission and passage of experimental “Kuru” to chimpanzees. Science 155, 212 (1967).Google Scholar
  31. and V. Zigas: Degenerative disease of the central nervous system in New Guinea. The endemic occurrence of “Kuru” in the native population. New Engl. J. Med. 257, 974 (1957).Google Scholar
  32. Gordon, W. S.: Proc. 63rd Ann. meeting U. S. Livestock San. Assoc. Scrapie 286 (1959).Google Scholar
  33. Gustafson, D. P., and C. L. Kanitz: Evidence of the presence of scrapie in cell cultures of brain. NINDB Monograph No. 2. Slow, latent and temperate virus infections. Ed.: D. C. Gajdusek, C. J. Gibbs, and M. Alpers (1965).Google Scholar
  34. Hadlow, W. J.: Scrapie and Kuru. Lancet 1959 II, 289.Google Scholar
  35. Jakob, A.: Symposium “Multiple Sclerosis” Locarno — to be published (1967).Google Scholar
  36. Kakulas, B. A., A. R. Lecours, and D. C. Gajdusek: Further observations on the pathology of kuru. J. Neuropath. 26, 85 (1967).Google Scholar
  37. Kidd, M.: Alzheimer's disease — An electron microscopic study. Brain 87, 307 (1964).Google Scholar
  38. Klatzo, I.: Neuropathological findings in kuru. NINDB Monograph No. 2. Slow, latent and temperate virus infections. Ed. D. C. Gajdusek, C. J. Gibbs, and M. Alpers (1965).Google Scholar
  39. D. C. Gajdusek, and V. Zigas: Pathology of kuru. Lab. Invest. 8, 799 (1959).Google Scholar
  40. McMullen, A. I.: A template mechanism for the biogenesis of specific polysaccharides. Excerpta Medica Internat. Congress Series No. 77 XIth Internat. Congress Cell Biology. N. Y. Excerpta Med. Foundation 32 (1964).Google Scholar
  41. Naftalin, R.: Effect on host cell RNA metabolism of EMC virus exposed to ultraviolet radiation. p. 15. Proc. Biochem. Soc. October 1967.Google Scholar
  42. Nature (Lond.) Editorial comment. 214, 755 (1967).Google Scholar
  43. Neumann, M. A., D. C. Gajdusek, and V. Zigas: Neuropathological findings in exotic neurologic disorders among natives in the highlands of New Guinea. J. Neuropath. 23, 486 (1964).Google Scholar
  44. Oosawa, F., M. Kasai, S. Hatano, and S. Asakura: Polymerization of actin and flagellin. In Principles of Biomolecular Organization. Ed. G. E. N. Wolstenholme, and M. O'Connor. London: Churchill.Google Scholar
  45. Palsson, P. A., I. H. Pattison, and E. J. Field: Transmission experiments with multiple sclerosis. NINDB Monograph No. 2. Slow, latent and temperate virus infections. Ed. D. C. Gajdusek, C. J. Gibbs, and M. Alpers (1965).Google Scholar
  46. Parry, H. B.: Scrapie: A transmissible and hereditary disease of sheep. Heredity 17, 75 (1962).Google Scholar
  47. Pattison, I. H.: Experiments with scrapie with special reference to the nature of the agent and the pathology of the disease. NINDB Monograph No. 2. Slow, latent and temperate virus infections. Ed. D. C. Gajdusek, C. J. Gibbs, and M. Alpers (1965).Google Scholar
  48. and K. M. Jones: The possible nature of the transmissible agent of scrapie. Vet. Record. 80, 2 (1967).Google Scholar
  49. Perier, O., and A. Gregoire: Electron microscopic features of multiple sclerosis lesions. Brain 88, 937 (1965).Google Scholar
  50. Pirie, N. W.: Biological Organization of Viruses. In Principles of Biomolecular Organization. Ed. G. E. N. Wolstenholme, and M. O'Connor. London: Churchill 1966.Google Scholar
  51. Pogo, B. G. T., V. G. Allfrey, and A. E. Mirsky: RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc. nat. Acad. Sci. (Wash.) 55, 805 (1966).Google Scholar
  52. Schapira, K., D. C. Poskanzer, and H. Miller: Familial and conjugal multiple sclerosis. Brain 86, 315 (1963).Google Scholar
  53. Raine, C. S., and E. J. Field: Orientated tubules in axoplasm of cerebellar myelinated nerve fibres in the rat. A study of normal and scrapie animals. Acta neuropath. (Berl.) 9, 298 (1967).Google Scholar
  54. Rivers, T. M., and F. F. Schwentker: Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J. exp. Med. 61, 689 (1935).Google Scholar
  55. Robbins, P. W., A. Wright, and M. Dankert: Polysaccharide biosynthesis. J. gen. Physiol. 49, 331 (1966).Google Scholar
  56. Savage, R. F., and E. J. Field: Brain damage and emotional behaviour: The effects of scrapie on the emotional responses of mice. Anim. Behav. 13, 443 (1965).Google Scholar
  57. Sigurdsson, B.: Observations on three slow infections of sheep. Brit. vet. J. 110, 255, 307, 341 (1954).Google Scholar

Copyright information

© Springer-Verlag 1967

Authors and Affiliations

  • E. J. Field
    • 1
  1. 1.Demyelinating Diseases Research UnitMedical Research CouncilNewcastle upon Tyne 2Great Britain

Personalised recommendations