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Electron microscope study on a transmissible cytotoxic factor isolated from cerebrospinal fluid of neurological patients: analysis of its structure and of its effects on various types of cell cultures
  1. D Guerra1,
  2. I Ronchetti1,
  3. F Beretti2,
  4. A M Bartoletti2,
  5. P Pietrosemoli2,
  6. M S Gelormini2,
  7. N Malagolini3,
  8. U Muscatello4,
  9. M Portolani2
  1. 1Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy
  2. 2Department of Laboratory Activities, Morbid Anatomy and Forensic Medicine, University of Modena and Reggio Emilia, Modena, Italy
  3. 3Department of Experimental Pathology, University of Bologna, Bologna, Italy
  4. 4National Research Center S3, Institute Nanoscience-CNR, Modena, Italy
  1. Correspondence to Professor Marinella Portolani, Department of Laboratory Activities, Morbid Anatomy and Forensic Medicine, University of Modena and Reggio Emilia, Policlinico, via del Pozzo, 71, 41124 Modena, Italy; portolani.marinella{at}


Aims In previous studies, the present group showed that a factor, present in the cerebrospinal fluid of seven neuro-patients, was capable of inducing cell damages on cell cultures of epithelial cells (Vero), glial cells (DG54-MG) and human primary lymphocytes. The cytotoxicity, once induced, could be transmitted to fresh cell cultures using crude preparations obtained from the cytotoxic cell cultures.

Methods and Results The present electron microscope study describes in detail the pathological changes occurring in the previously assayed cultured cell types, and for the first time in human fibroblasts, as a consequence of the treatment with crude cytotoxic preparation. It also demonstrates with reasonable certainty the absence of virus-like particles in both the treated cells and the partially purified cytotoxic fraction. Indeed high-resolution electron microscopy analysis shows that this fraction consists almost entirely of protein spheroids with a diameter of 8–12 nm.

Conclusions The possible significance of nanotubular aggregates, observed in particular in the glial and in the epithelial cells undergoing cytotoxic damage, is also discussed.

  • Cytotoxic cerebrospinal fluid
  • in vitro transferable cytotoxicity
  • ultrastructural features of cytotoxicity
  • cell cultures
  • morphology
  • neuropathology
  • virology
  • reports
  • diagnosis

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  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by informed consensus.

  • Provenance and peer review Not commissioned; externally peer reviewed.