Pathogenesis 469 



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 1 : 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. , 



Neufeld and Doddf followed by RosenowJ obtained a toxic fluid by 

 permitting the pneumococci to undergo autolysis either in lecithin- 

 ized or plain physiological salt solution. Cole§ found that the 

 toxic values of such extracts was not uniform, but that autolysates 

 of pneumococci in dilute solutions of bile salts were very uniform in 

 strength, and possessed hemolytic effects upon the blood-corpuscles 

 of human beings, rabbits, sheep and guinea-pigs. This hematoxic 

 substance produced immunity reactions when repeatedly injected 

 into animals in increasing doses, antihematoxin being produced. 

 The toxin liberated by autolysis was found by Rosenow, |1 to be soluble 

 in ether. Heating the clear autolysate to 6o°C. for twenty minutes 

 destroys it, though toxic pneumococcus suspensions remain toxic even 

 after boiling. Hydrochloric acid in weak solutions destroys the toxic- 

 ity of pneumococcus autolysates. The toxic substance is absorbed 

 by blood charcoal from which it can again be obtaiiied by shaking with 

 ether. The toxic substance 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." Rosenow** found 

 that the autolysate contained a proteolytic enzyme. He alsofoundft 

 that it was capable of producing, in dogs, symptoms strikingly like ana- 

 phylaxis, with a striking drop in the blood pressure, pronounced 

 hemorrhages, marked depression of respiration, extreme cyanosis and 

 the presence of CO2 in the stomach. 



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

 lent organism 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. 



* "Centralbl. f. Bakt. u. Parasitenk.," 1907, Orig. xliii, p. 30. 



t "Berl. klin. Wochenschrift," 1911, xlviii, io6g. 



t "Journal of Infectious Diseases," 1911, rx, 190. 



§ "Jour. Exp. Med.," 1912, xvi, 644. 



II "Journal of Infectious Diseases," 1912, xi, 94, 235. 

 ** "Journal of Infectious Diseases," 1912, xi, 286. 

 ttlbid., p. 480. 



