^^12 LOCAL TLSSUE REACTlVrFY 



may l)e ()l)scr\t'(l lrc'(jiicnt (lis(liart;c ol (liiid stool. Ihis is accoiii- 

 paiiic'd by a pioiiouiued mcteriorism. There may also occur 

 clonic contractions and in others, paralysis of the extremities. 

 The respiration and the activity of the heart fail. Pronounced 

 cyanosis precedes death. The entire picture may occin- Avithin a 

 few hours. The sid)acute intoxication differs from the above 

 acute form only in the intensity of the symptoms \viiich, however, 

 does not necessarily depend on the amount of the filtrate injected. 

 Rabl)its suffering- from the sid)acute intoxication may not show- 

 any symptoms vvithin a few liours following the injection. It is 

 only dining the following day that there occin- a slight Aveakness 

 of the muscidar tonus and loss of apj)etite. The rectal tempera- 

 ture drops by 0.5*= to 1° c, or in other instances may be raised 

 that much. Occasionally, Stolyhw(^ was able to obserxe a prolonga- 

 tion of the pulse rate. I^etween the third and seventh day follow- 

 ing the injection, the respirations become very weak and symp- 

 toms similar to those of acute intoxication dexelop preceding 

 death. In rare instances death occurs ten to iointeen days fol- 

 lowing the injection. The rabbits by that time develop severe 

 cachexia. 



The lethal factors of properties just described are foiuid in high 

 concentration in meningococcus and B. typhosus "agar vvashings" 

 filtrates; and in lesser concentration, in other filtrates employed 

 in this work. The lethal effect can be obtained ^vith sufficient doses 

 in 50 to 75 per cent of ral)bits injectecL The data are derived 

 from experiments ^vith many thousands of rabbits. The imjjres- 

 sion -^vas also gained by me that the concentration of the lethal 

 factors somewhat parallels the concentration of acti\'e principles 

 in filtrates derived from organisms capable of ]:)rodiuing active 

 principles of high potency. It also happens not infrecpiently that 

 hltrates stored for a ])rolonged period of time in the refrigerator 

 and losing the active principles undergo a roughly proportionate 

 loss in the lethal potency. The parallelism is not o])served, hoAv- 

 ever, in filtrates producing active principles of \ow concentration. 

 Thus, certain streptococcus and pneumococcus culture filtrates 

 are able to kill rabbits in doses insufficient for production of the 

 phenomenon. 



There is convincing evidence that the lethal factors of the 

 "agar washings" filtrates are specifically neutralized by immune 

 sera. Normal sera fail to inactivate these factors and even occa- 

 sionally seem to contribute to the general toxicity of the filtrates. 



