216 WARFIELD T. LONGCOPE AND GEORGE M. MACKENZIE 



of non-specific protease; (b) a decrease in anti-ferment; (c) increase 

 in the non-coagulable nitrogen of the serum; (d) increase in amino acids; 

 (e) decrease in serum proteose. (4) Later there is a progressive increase 

 in the non-coagulable nitrogen, proteose and lipase of the serum. From 

 these experimental results, they formulate a theory of the mechanism 

 of anaphylactic shock which departs from current conceptions. They be- 

 lieve that acute intoxication is brought about by the cleavage of serum 

 proteins, including proteoses, through the peptone stage by a non-specific 

 protease. The least convincing part of their argument is the explanation 

 offered for the specificity of anaphylactic reactions. They say, "The 

 specific elements lie in the rapid mobilization of this ferment and the col- 

 loidal serum changes which bring about the change in anti-ferment titre." 



The aim of these studies was to elucidate the problem of the mechan- 

 ism of anaphylaxis, and even though they may not suffice to clear this 

 difficult problem, they are nevertheless of importance from the point of 

 view of the metabolic disturbances associated with anaphylactic phe- 

 nomena. 



If serum be added to a mixture of a protein and a proteolytic enzyme, 

 present in the mixture in such proportions that the enzyme will completely 

 hydrolyze the protein, the anti-proteolytic power or antitryptic titre of 

 the serum is manifested by the extent to which hydrolysis of the protein 

 is inhibited. If an anti-proteolytic substance be present in the serum 

 unsplit protein will be present when equilibrium is reached. 



So far as we are aware, the earliest attempt to bring alterations in the 

 anti-ferment titre into relation with anaphylaxis was made in 1912 by 

 Ruszniak. Sensitizing guinea pigs with egg white and allowing an incuba- 

 tion period of 2-4 weeks, he withdrew blood about 15 minutes after the 

 reinjection. He found that in normal animals, the anti-ferment titre was 

 40-50, while in anaphylaxis it was 70-110. On the basis of the demonstra- 

 tion by Bayliss that split products inhibit the action of specific ferment 

 on account of the reversibility of the enzyme reaction, and absorption of 

 the ferment by split products, Ruszniak offers his results as further evi- 

 dence of protein cleavage in anaphylaxis. Rosenthal, indeed, brought 

 forward evidence that the normal antitryptic power of the serum is de- 

 pendent upon the amino acids present. 



The results of Ruszniak, even though they are in harmony with con- 

 clusions reached by others and theoretically are plausible, cannot be ac- 

 cepted without confirmation ; especially because both Seligman and Ando, 

 each using a technique almost identical with that of Ruszniak, failed to 

 find any increase in the anti-ferment titre of the serum. 



Non-Specific Alteration of the Degrees of Hypersensitiveness. 

 Owing to the obscurity which still surrounds to a large extent the 

 mechanism of anaphylaxis, the mode of action of those substances which 



