Pathogenesis 449 



upon the bottom of the culture-glass, it neutralized the lactic acid 

 produced by the pneumococcus, and enabled it to grow better and 

 produce much stronger toxin. Macfadyen* found that by freezing 

 cultures of the pneumococcus with liquid air, destroying them 

 by trituration in the frozen state and then extracting the frag- 

 ments with I : 1000 caustic potash solution, a toxin whose activity 

 corresponded fairly well with the virulence of the culture could be 

 secured. This toxin killed rabbits and guinea-pigs in doses varying 

 from 0.5 to I cc. 



It is undoubtedly an endotoxin that is liberated from the bodies of 

 the pneumococci as they undergo autolysis or are dissolved by the 

 enzymic action of the body juices or the cells. The toxin liberated 

 by autolysis has been carefully studied by Rosenow,t who "finds it 

 soluble in ether. It is formed during retrogressive changes in the 

 pneumococci. Heating the clear autolysate to 6o°C. for twenty 

 minutes destroys it, while toxic pneumococcus suspensions remain 

 toxic even after boiling. Hydrochloric acid in weak solutions de- 

 stroys the toxicity of pneumococcus autolysates. The toxic sub- 

 stance is absorbed by blood charcoal from which it can again be 

 obtained by shaking with ether. Autolyzed virulent pneumococci 

 and non-virulent pneumonia diminish the toxicity slightly while 

 unautolyzed virulent pneumococci increase it. The toxic sub- 

 stance is probably a base which contains amino groups of nitrogen. 

 Indications have been obtained showing that during pneumococcus 

 infections toxic substances are produced that do not call forth any 

 immunizing response." Rosenowf found that the autolysate con- 

 tained a proteolytic enzyme. He also found§ that it was capable 

 of producing, in dogs, symptoms strikingly like anaphylaxis, with 

 a striking drop in the blood pressure, pronounced hemorrhages, 

 marked depression of respiration, extreme cyanosis and the pres- 

 ence of CO2 in the stomach. 



Pathogenesis. — If a small quantity of a pure culture of the viru- 

 lent organisni be introduced into a mouse, rabbit, or guinea-pig, the 

 animal dies in one or two days. Exactly the same result can be ob- 

 tained by the introduction of a piece of the lung-tissue from croupous 

 pneumonia, by the introduction of some of the rusty sputum, and 

 frequently by the introduction of human saliva. Postmortem ex- 

 amination of infected animals shows an inflammatory change at the 

 point of subcutaneous inoculation, with a fibrinous exudate similar 

 to that succeeding subcutaneous inoculation with the diphtheria 

 bacillus. At times, and especially in dogs, a little pus may be found. 

 The spleen is enlarged, firm, and red-brown. The blood with which 

 the cavities of the heart are filled is firmly coagulated, and, like that 

 in other organs of the body, contains large numbers of the bacteria, 



* Ibid., igo6, li. 



f'Journal of Infectious Diseases," 1912, x. 94, 235. 



i "Journal of Infectious Diseases," 191 2, x. 287. 



§ Ibid., p. 480. 

 29 



