HYPERSENSITIVENESS, PROTEIN INTOXICATION 211 



protein, if the possibility of retention by damaged kidneys has not been 

 eliminated. 



It is therefore important to consider the studies of protein metabolism 

 in which the factor of renal function is not involved. Investigators seek- 

 ing to discover the ultimate anaphylactic mechanism have helped to solve 

 this problem of nitrogen metabolism in anaphylaxis. Manwaring's im- 

 portant series of experiments, referred to above, on the reaction of the 

 tissues and organs concerned in protein digestion and assimilation first 

 drew attention to the crucial part which the liver plays in canine anaphy- 

 lactic reactions. Manwaring found that "if temporary sutures are placed 

 around the aorta and vena cava, above the diaphragm, the upper half of 

 the anaphylactic body will not react to a serum injection. The supra- 

 diaphragmatic tissues and organs, therefore, are not primarily concerned 

 in anaphylaxis." Release of the ligatures is followed by typical shock. 

 He removed all the abdominal viscera, except the liver, and the sensitized 

 animal still responded to reinjection by typical shock. "We are therefore 

 forced to conclude," he says, "that the essential primary organ is the only 

 remaining viscus, the 'liver." Further work seemed to indicate that the 

 intestines and attached pancreas constitute a second primary anaphylactic 

 mechanism. In the light of these results the contribution of Hashimoto 

 and Pick is interesting. They found that the non-coagulable nitrogen in 

 the livers of normal guinea-pigs forms about eight per cent of the total 

 nitrogen. In the livers of sensitized animals they found that the non- 

 coagulable nitrogen formed about 22 per cent of the total nitrogen. In the 

 kidneys, brain, spleen and blood they found no such differences between 

 normal and sensitized animals. They found, too, that following the sensi- 

 tizing dose, the percentage of non-coagulable nitrogen of the liver increased 

 up to the fourteenth day and then decreased. Interesting as these results 

 are, they require confirmation, because Barger and Dale(&), in an effort to 

 confirm them, used the same technic and could detect no noteworthy differ- 

 ence between normal and sensitized animals so far as the non-coagulable 

 fraction of the total nitrogen was concerned. Experiments of the same 

 type were done by Auer and Van Slyke. They determined the amino nitro- 

 gen content of the lungs of guinea-pigs after anaphylactic shock. No sig- 

 nificant difference between anaphylactic and control guinea-pigs could be 

 demonstrated. Moreover, they showed that fluctuations in the amino nitro- 

 gen figures amounting to one-third of that present may occur in animals 

 kept under approximately the same conditions. 



Recent work by Rumpf has supplied evidence indirectly confirming 

 the results of Manwaring's work on the site of the anaphylactic reaction 

 and at the same time has supplied additional support for the cellular 

 theory of anaphylaxis. In perfusion experiments on the excised livers of 

 sensitized and normal guinea-pigs, he studied the urea formation with and 

 without the addition of specific antigen. His results are summarized as 



