NATURE OF THE ACTIVE PRINCIPLES 315 



that in their hands, the reactions following the intravenous in- 

 jection in sites prcjxned \\ith diluted endotoxin preparations 

 were first and conspicuously hemorrhagic. The primary reactions 

 produced ^\■ith strong concentrations of the same preparations 

 were more of a necrotic and inflammatory type ^vith hemorrhages 

 developing at a later stage. 



These authors did not carry out any c^uantitative titrations in 

 order to determine the relationship of the skin necrotizing sub- 

 stances to the phenomenon-producing principles. As is known, 

 the "agar washings" hltrates possessing a high phenomenon-pro- 

 ducing potency elicit only slight primary reactions in the skin. 

 The method of Malcolm and WHiite apparently was successful in 

 i)ringing aboiu the concentration of the primary skin-injurious 

 factors. If the latter factors ^vere identical \vith the phenomenon- 

 j^roducing factors, it should be expected that incidentally there 

 be present in their preparations a considerably higher concen- 

 tration of phenomenon-producing factors than in the "agar 

 washings" filtrates. 



Platit's Spirocheta pallida materials endo^ved ^vith phenomenon- 

 jnoducing potency induced cachexia in rabbits following the 

 intravenous injection of large doses. Intracranial injections of 

 small amotmts were highly toxic (0.2 to 0.3 c.c.) and killed the ani- 

 mals ^vithin t^vo to three days. In his experiments there seemed 

 to be a definite parallelism betw^een the general toxicity and phe- 

 nomenon-producing potencies. Non-dialyzed cultures Avere in- 

 nocuous to rabbits and failed to produce the phenomenon ^vhilst 

 the dialyzed cultures contained the active principles of the phe- 

 nomenon and killed the rabbits. The dialyzed material elicited 

 clonic convtilsions in mice. The non-dialyzed material produced 

 no effect. 



P. Boquet's active principles of B. lepisepficus also possessed a 

 lethal effect although in large doses. 



The potent phenomenon-producing preparations of B. abort us 

 of ZuAverkalow, Fischbein and Juranoff (1935) gave symptoms 

 (pronounced cachexia) of general intoxication in rabbits ^vith 

 positi\e local reactions. The organs of the dead animals ^vere 

 sterile. No toxic effect was noticed in mice. 



Phenomenon-producing filtrates of Vibrio cJiolerae described 

 bv Linton, Singh, and Seal (1935) in doses of 1 to 1.5 c.c. were 

 well supported by Belgian rabbits. Albino rabbits of the same 

 weight were highly susceptible to the filtrates. One-tenth c.c. killed 



