view is urged by Frederikse, who finds that the presence or absence of serum-globulin in such mixtures makes no difference in the amount of fibrin formed. He also confirms Hammarsten's statement, that fibrinogen is split into fibrin or coagulated proteid and a soluble globulin by the action of fibrin ferment; the same decomposition is said to be brought about by the action of dilute acetic acid. up Lilienfeld regards the active agent in coagulation as a nucleo-albuminous substance, named nucleohiston, which arises from the leucocytes, especially from their nuclei, and from platelets. In this substance the nuclein hastens while the histon hinders the coagulation, the separation into nuclein and histon being effected by calcium salts. From fibrinogen he has obtained a substance, thrombosin, by precipitation with acetic acid and nuclein, or rather nucleic acid, which acts in the same way; thrombosin is coagulated by calcium salts, and the fibrin so formed is regarded as a calcium compound of thrombosin. Schäfer has criticised these assertions of Lilienfeld's, stating that further evidence is necessary to show that thrombosin and fibrinogen are different substances; also that Lilienfeld does not prove that nucleo-albumin does not enter into the reaction, for it is impossible to prepare fibrinogen quite free from nucleo-albumin. Hammarsten and Cramer also consider that thrombosin is the same as fibrinogen. In the same publication, Hammarsten shows that calcium salts are not essential for the formation of fibrin from fibrinogen, since they both contain the same amount of calcium, and he confirms Pekelharing, that calcium salts act in the genesis of fibrin ferment, i.e. in the change of prothrombin, the precursor of fibrin ferment, into thrombin, the fibrin ferment. The formation of fibrin from fibrinogen is usually regarded as a process of hydrolysis, the fibrinogen being converted into fibrin and fibrinoglobulin (Arthus). Hammarsten has found that the elementary composition of these substances is very similar, and he brings forward the view that the change may consist in an intramolecular rearrangement in the fibrinogen, part of it appearing as fibrin, and part remaining in solution as fibrinoglobulin. Under several other conditions, besides that of the removal of calcium salts, blood can be prevented from clotting, e.g. by leech extract, albumoses, peptones; and many experiments have been made in order to elucidate the manner in which fibrin is formed, but these do not throw any more light upon this important change. The following facts, however, still remain proved: nucleoproteid (or prothrombin) combines with calcium to form fibrin ferment, which then acts upon fibrinogen, and causes the formation of fibrin, which constitutes the coagulum. The facts can be tabulated thus: Fibrinogen Nucleoproteid Calcium salt } = fibrin ferment = fibrin CHAPTER XVI. CHANGES IN MILK, MUSCLE, AND IN THE LIQUID OF THE PROSTATE GLAND. A TRANSFORMATION, very similar in many ways to the coagulation of blood, is carried out daily in the manufacture of cheese from milk. This change is produced by the action of rennin, a soluble ferment or enzyme contained in calves' stomachs, from which it can be extracted to form rennet. Milk contains three proteids-caseinogen, lactalbumin, lactoglobulin, the two latter only in small quantities; also milk, sugar, fat, calcium phosphate, and other salts. Cheese is obtained from the caseinogen, which forms the curd, which contains the fat mechanically; the other proteids, the sugar, and the salts are contained in the liquid which constitutes the whey. The action of the rennin was supposed in 1859, by Liebig, to be the conversion of lactose into lactic acid; this neutralised the alkali which kept the caseinogen in solution, thus causing its precipitation. This idea evidently arose from the fact that acids, when added to milk, produce a precipitation of the caseinogen. Soxhlet held a very similar view, but he took into account the presence of the calcium phosphate; this was converted by the lactic acid, obtained from lactose by the action of rennin, into acid calcium phosphate, which precipitated the caseinogen. The most important work upon the coagulation of milk is that of Hammarsten, who has shown that the lactose takes no part in the change, and that the clot can even be formed in an alkaline medium, as first pointed out by Selmi. The presence of calcium was found essential for the conversion, and Ringer states also that other calcium salts than the phosphate can be used. The production of casein is a double process; in the first instance the caseinogen is converted into soluble casein by the rennin, and secondly the casein is precipitated by calcium, probably as calcium salt or caseate of lime (Halliburton). Hammarsten considers that in the process the caseinogen is split into two parts-the insoluble casein and the whey proteid, which is soluble. This change can be tabulated thus Caseinogen Calcium salt Rennin } = soluble casein = casein and is therefore slightly different from that which occurs in blood, where the calcium takes part in the first stage of the change. The similarity between the formation of fibrin in the clotting of blood and the production of rigor mortis in muscle, was first pointed out by Kühne, and he made the first investigations upon this change, about the year 1860. From frog's muscle at a temperature of 0° C., he obtained a plasma which possessed the power of coagulation; in very much the same way as in blood and milk, this clot contracted and gave a serum, but, instead of being fibrinous, this coagulum remained gelatinous and soft. The term "myosin" was given to it. Halliburton has obtained the same results with plasma obtained from the muscles of rabbits and other animals, and he has shown that the myosin obtained, if redissolved after coagulation, could be made to clot even three or four times. He states that a ferment, which he has isolated, is the cause of this change, and he has called it myosin ferment. From the plasma he has obtained four proteids, which he has named paramyosinogen, myosinogen, myoglobulin, and myoalbumin; and he has shown that the coagulation is caused in the myosinogen, which carries down with it on coagulation the paramyosinogen. He considers that the myosinogen does not split up into two proteids, as is supposed to happen in the case of fibrinogen; in the coagulation, however, sarcolactic acid is formed and carbon dioxide is evolved, thus: Myosinogen Myosin ferment} = myosin +CO2+CH-CHOH-COOH Von Fürth has also carried out investigations upon the subject, and has obtained two proteids from muscle plasma:—(1) Paramyosinogen, constituting 17-22 per cent., and (2) myosinogen or myogen, constituting 77-83 per cent. of the plasma; this latter corresponds to Halliburton's myosinogen. These two proteids enter into the formation of the clot; paramyosinogen passes directly into myosin fibrin, but myosinogen or myogen passes |