A relatively simple preparation of guinea pig brain myelin, free of gross contamination by other cellular elements has been described. Electron microscopic evidence of the predominance of membranous (lamellar) forms was used as the criterion of purity of this fraction. The slight mitochondrial contamination of the myelin fraction was confirmed by its low succinic dehydrogenase activity. Quantitative bio-assay of the encephalitogenic activity of myelin showed it to have a higher specific activity than whole guinea pig brain. The low encephalomyelitic activity of the other subcellular constituents (nuclei and mitochondria) which were removed from myelin by ultracentrifugation in 30 per cent sucrose could be explained by a small amount of myelin contamination. A basic protein of high specific encephalitogenic activity has been isolated from myelin by methods previously applied to whole brain. Although the protein is similar to nuclear histones, the following facts point to certain significant differences. Nuclei prepared by a different procedure from the one developed for the isolation of myelin were found to be non-encephalitogenic. Although basic protein could be extracted readily from these nuclei by dilute HCl, the same extraction procedure yielded little extractable protein from whole myelin. Myelin which had been defatted by cold chloroform-methanol yielded a basic protein which was highly encephalitogenic. The evidence presented thus supports the view that there exists in myelin a new basic protein responsible for the induction of experimental allergic encephalomyelitis, which is distinctly different from nuclear histones. The possible relationship of this protein to myelin structure and function has been discussed.

Animals↗

PubMed1962

Prevention of experimental allergic encephalomyelitis (EAE) by vitamin C deprivation.

Scorbutic guinea pigs injected with CNS and mycobacterium to induce experimental allergic encephalomyelitis (EAE) showed no clear-cut neurological signs and failed to show histological evidence of central nervous system damage. The degree of protection afforded by vitamin C deprivation was related directly to the duration of the scorbutogenic diet and inversely to the strength of the CNS challenge. Vitamin C deprivation also abolished tuberculin sensitivity as measured by the PPD skin reaction. Upon restoration of vitamin C, the animals recovered their sensitivity to PPD but did not develop EAE. It was further demonstrated that these effects of vitamin C deprivation were not related to inanition or to the endogenous levels of 17-hydroxycorticosteroids.

Animals↗

PubMed1962

Adjuvant-antigen relationships in the production of experimental "allergic" encephalomyelitis in the guinea pig.

Quantitative relationships between the amounts of encephalitogenic neural tissue and mycobacterial adjuvant are presented for the guinea pig, for comparison with similar results obtained in the mouse and presented in an accompanying paper by Lee and Schneider (27). Definite threshold amounts of both neural encephalitogenic and mycobacterial adjuvant can be defined. With the proper amounts of each component, 100 per cent of guinea pigs can be made to develop EAE, 97 per cent dying of it, and over 50 per cent becoming paralyzed by the 12th day after challenge. With moderate amounts of encephalitogen the severity and incidence of EAE can be very great, but this encephalitogenic potential can be masked if large amounts of mycobacteria are employed. The mechanism of this masking effect by excess adjuvant is not known, but speculation centers upon the possibility of competition of antigens of the mycobacteria at the expense of those of the encephalitogen.

Adjuvants, Immunologic↗