CURRENT STATUS OF CELLULAR TRANSFER OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS: A CRITIQUE.
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Biomedical subjects
Publications and source records attributed to H A SCHNEIDER.
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The production of EAE in the fully susceptible BSVS mouse genotype has been found to be dependent on the ratio of proteolipid antigen and adjuvant mycobacterial concentration as used in the emulsion, of the Freund type. Disturbance of this ratio, by manipulation of either component, by diminution or increase, results in a decrease in the frequency by which EAE is produced. Simultaneous reduction of antigen and mycobacteria, so that the ratio remains unchanged, retains the full EAE-producing power of the emulsion. The limit of this has not been ascertained. Emulsifying agents have been found to restrict further the permissible limits of the antigen-mycobacterial ratio for full EAE production. Such effects of the emulsifier have been found to vary with the qualitative nature of the emulsifier. Aquaphor has been found to be less restrictive than falba. These phenomena, systematically analyzed here for the mouse, may have an application for other antigen-adjuvant systems and for other hosts.
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The localized Shwartzman reaction has been demonstrated in a highly inbred mouse strain (BSVS). This reaction was produced with marked regularity in these mice by administration of relatively small doses of bacterial endotoxin or other Shwartzman-active agents. It is considered the equivalent of the phenomenon described in the rabbit inasmuch as it has conformed to all the operational and histopathological aspects of the classical reaction that have been tested, including elicitation by various endotoxins, heterologous preparation and provocation, inhibition by anticoagulants, and provocation by antigen-antibody complexes. A reaction similar to the above but differing in its manner of production was also investigated and has been termed the single-injection Shwartzman reaction. This phenomenon was identical with the normal Shwartzman reaction in all ways except for the fact that it was elicited with but a single intradermal injection of bacterial endotoxin. In investigating the lesion it has been demonstrated that inapparent in the gross, but elicitible infection of the lungs with a Gram-negative microflora was uniformly associated with single-injection reactivity. Because of this constant association it has been suggested that a causal relationship exists between the infected state and the skin reaction, not on the basis of known immunological events but on the basis of the Shwartzman mechanism in which the lung flora, demonstrably excited by the preparative injection, appears to mediate natural "endogenous" provocation of the lesion at the prepared skin sites.
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Susceptible (BSVS) and resistant (BRVR) mice were experimentally infected with Salmonella typhimurium. The double strain inoculation technique was used in which both avirulent and virulent representatives of S. typhimurium were admitted into the hosts. The BSVS mice succumbed without exception while the BRVR mice survived to 52 per cent. No deaths occurred during the experimental period in non-infected control mice. Parallel to the survivorship test, and concurrent with it, the activity of the reticulo-endothelial system (RES) was measured at frequent intervals in identically infected BSVS and BRVR mice and in their non-infected controls. For this measurement the carbon clearance method was used. No pre-infection difference of activity of the RES could be discerned in susceptible BSVS mice vs. resistant BRVR. Following infection, increases in the RES activity were detected in about the same magnitude in both mouse stocks. However, a difference was found in the time of onset. The susceptible animals showed an early and short increase in the activity of the RES, followed by a drop to control levels at the time of death. The resistant group exhibited a considerably delayed, but significant increase in RES activity, which returned to control levels approximately 4 weeks after infection. The absolute white blood count did not undergo significant change in either of the two infected groups, but the susceptible animals showed a relative increase of their neutrophils at the expense of their lymphocytes. Extensive anatomical changes were observed in both mouse strains, mainly confined to liver and spleen. These consisted of stasis, swelling of Kupffer cells, necrotic foci, histiocytic-monocytic nodules, widespread thrombosis of branches of the portal and splenic veins, and extensive areas of necrosis. These changes appeared earlier in susceptible than in resistant animals. The implications of these findings are discussed.
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The susceptibility of homozygous BSVS mice to acute disseminated encephalomyelitis (ADE) has been found to be nutritionally dependent. On a laboratory stock regimen of commercial fox chow pellets, whole wheat bread, and milk this genotype is 100 per cent susceptible to the disease. On a "synthetic" diet, containing a minimal list of vitamins adequate for growth and maintenance, susceptibility was found to be reduced to 15 per cent. Supplementation of the "synthetic" diet with biotin, folic acid, and vitamin B(12) restored susceptibility to a frequency of 70 per cent. Increasing the supplements tenfold had no further effect in restoring susceptibility frequencies to the 100 per cent level. In the restoration of susceptibility, folic acid and vitamin B(12) were equally effective as single supplements and equivalent to the triple vitamin supplement. The effect of single biotin supplementation was less. An outbreak of fatal pasteurellosis among BSVS mice latently infected with Pasteurella and used in an ADE susceptibility test has been described. The fatal pasteurellosis has been ascribed to a constellation of determinants including (a) diet, (b) sex, (c) inoculation events, and (d) latent infection with Pasteurella. With males the susceptible sex it was possible to avert the fatal pasteurellosis and continue the nutritional experiments by using females exclusively.
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The double strain inoculation test as used for the assay of nutritional factors capable of enhancing survivorship in mouse salmonellosis has been modified and improved. The modification has been based on the use of genetically marked strains of S. typhimurium, and substitutes for survivorship a bacteriological datum, a certain minimum population size of the virulent salmonellae in the mouse spleen at a certain time. The analysis permitting this substitution and the economies achieved by the modification has been presented. In the course of development of the new assay evidence was obtained that the nutrient entity or entities responsible for enhanced survivorship, as measured by the bacteriological correlate, are not stored in the mouse. A deficiency state was achieved 24 hours after supplying the basal synthetic diet. Similarly, positive effect of active nutrients was evident as soon as 24 hours after feeding.
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