1. The serum ferments are practically unaltered by a primary injection of foreign protein. 2. During the course of sensitization the injection of the antigen is followed by the mobilization of a non-specific protease which increases in rapidity and intensity as the maximum period of sensitization is reached. 3. Acute shock is accompanied by: (a) The instantaneous mobilization of a large amount of non-specific protease; (b) a decrease in antiferment; (c) an increase in non-coagulable nitrogen of the serum; (d) an increase in amino-acids; (e) a primary decrease in serum proteoses. 4. Later there is a progressive increase in the non-coagulable nitrogen, in proteoses, and in serum lipase. 5. The acute intoxication is brought about by the cleavage of serum proteins (and proteoses) through the peptone stage by a non-specific protease. 6. The specific elements lie in the rapid, mobilization of this ferment and the colloidal serum changes which bring about the change in antiferment titer.
1. After feeding, an increase in non-coagulable nitrogen of the serum can be determined, reaching a maximum in about six hours. 2. This increase is greatest in the portal blood and is partially due to an increase in amino-acids. There is no increase in proteoses. 3. There is usually a progressive decrease in serum protease, reaching a minimum after from five to seven hours. 4. The portal blood may show an unaltered or an increased amount of protease. 5. The serum antiferment shows a slight increase, but is subject to considerable fluctuation. 6. The serum lipase (esterase) shows a slight increase, reaching a maximum after three hours. The hepatic blood usually contains the lowest concentration of lipase.
In an extended series of papers Kirchheim ( I ) h a s studied the question of the toxicity of trypsin in both its local and general effects. The resistance of living tissue to the local effect of trypsin has also been studied by Langenski61d (2) and by Marie and Villandre (3). Kirchheim called attention to the similarry of trypsin intoxication to anaphylactic and peptone shock. He determined that the toxicity was destroyed when the ferment was inactivated by heat and that the fresh pancreatic secretion was not toxic unless activated by enterokinase. He concluded therefrom that the toxicity was not due to admixed protein split products. In order to determine whether the toxicity depended upon the effect of the ferment directly on the living cell, or whether split products were first formed from soluble proteins, in this way leading to an indirect intoxication, Kirchheim tried the effect of the ferment directly on spermatozoa. Since he found, however, that the spermatozoa were injured neither by the ferment nor by split products produced by the action of the ferment, Kirchheim drew no definite conclusion. In his work on the serum antiferment Kirchheim showed that both theories held (split products in the serum, and true antibody formation) were erroneous. Incidentally he noted that chloroform rendered the serum albumin more digestible by trypsin.In view of the similarity of trypsin intoxication to anaphylactic and peptone shock we have undertaken a series of experiments to determine the effect of the ferment when injected into the blood stream of dogs. The trypsin used was either commercial pancreatin (for intestinal injection) or purified according to the method previously described (4). The latter ferment was very active and when dried retained its strength unimpaired. The serum ferments were titrated according to the method described fully in a previous paper 141 on
1. Liver tissue showing fatty degeneration obtained from animals poisoned with phosphorus or chloroform contains a decreased amount of esterase. 2. The serum of animals poisoned with phosphorus or chloroform has a high esterase activity. 3. The increased amount of esterase in the serum is not derived from the disintegrating liver cells as the esterase in the blood of the hepatic vein is less than that found elsewhere.
In previous papers we have discussed the ferment changes that occur in dogs during trypsin, anaphylactic, and kaolin shock, noting more particularly the relation of the serum protease to the antiferment and to the split products contained in the serum, together with changes in the lipase content. In the present paper we shall present the resulting ferment changes following the injection of various protein derivatives.The fundamental ideas of Vaughan 1 relating to the toxicity of protein split products have been fully developed during the course of the last few years; the only element of uncertainty lies in the interpretation of certain phases of specificity of ferments which are supposed to split the native protein to toxic fragments. According to Vaughan's hypothesis, specific protease is produced capable of such function, a supposition which has received much support from the work of the Abderhalden school. There is, however, certain experimenthl evidence to the contrary, indicating that the specific dement is not due to specific ferment action, but rather that the splitting that occurs is due to a non-specific ferment; that the split products are largely derived from the serum proteins and not from the injected antigen; while the element of specificity lies in the colloidal changes which bring about a lowering of the antiferment titer and in the rapid mobilization of the protease.
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