422 RETROGRESSIVE CHANGES 



Kekule showed that the substance in question was of protein nature; 

 their methods were very crude, but the main fact was soon better 

 substantiated by Klihne and Rudneff (1865). Krawkow,^'' however, 

 in 1897 gave us the first good idea of the composition of amyloid sub- 

 stance through his ampKfication of Oddi's^^ observation that amyloid 

 organs contain chondroitin-sulphuric acid, finding that amyloid is a 

 compound of protein with this acid, similar to nucleoprotein, which 

 is a compound of nucleic acid and protein. This work has received 

 general acceptance, although a later paper by Hanssen^^ reports a 

 study of amyloid material isolated in pure condition from sago spleens 

 by mechanical means, which contained no chondroitin-sulphuric acid, 

 although the amyloid organs taken in toto do contain ah excess of sul- 

 phur as sulphate. This important contradiction to prevailing ideas 

 has not, so far as I can find, been subjected to investigation by others, 

 with the exception of a casual remark by Mayeda^^ that a prepara- 

 tion of amyloid which he had made did not yield sulphuric acid. 



Chondroitin-sulphuric acid, which has been studied especially by Morner and 

 by Schmiedeberg,^^ has the formula C18H27NSO17, according to tlie latter, and 

 yields on cleavage chondroitin and sulphuric acid, as follows. 



Ci8H27NSOn+H20 = C18H27NO14+H2SO4 

 Kondo,^^ however, gives it an empirical formula of C15H27NSO16, there being ap- 

 parently two equivalents of the base for each SO4 group. Levene and La Forge'^ 

 have demonstrated that chondroitin-sulphuric acid consists of sulphuric acid, 

 acetic acid, chondrosamine which is an isomer of glucosamine, and glucuronic 

 acid. It unites with histones and forms a precipitate.^^ Chondroitin is a gummy 

 substance which in turn may be split into acetic acid and a reducing substance, 

 chondrosin. Chondroitin-sulphuric acid is the characteristic component of car- 

 tilage, but it is also found in the walls of the aorta and other elastic structures 

 (Krawkow). It has also been found in a uterine fibroma and in bone tissue by 

 Krawkow, but could not be found in the parenchymatous organs, normal and 

 pathological, or in chitinous structures. Morner has also found it in a chondroma. 



Chemistry of Amyloid. — Krawkow separated amyloid from nu- 

 cleoprotein, to which it is most closely related, by dissolving both sub- 

 stances from the minced amyloid organs with ammonia, precipitating 

 with acid, and then taking up the amyloid with Ba (OH) 2 solution, in 

 which the nucleoprotein does not dissolve. Amyloid thus isolated is 

 a nearly white powder, which is easily soluble in alkalies, but slightly 

 in_^acids, and is very resistant to pepsin digestion. The elementary 

 composition was found by Krawkow to be approximately as follows : 

 C = 49-50%; H = 6.65-7%; N = 13.8-14%; S = 2.65-2.9%; P in 

 traces only. 



^» Arch. exp. Path. u. Pharm., 1897 (40), 196. 



31 Ibid., 1894 (33), 377. 



32 Hiochem. Zcit., 1908 (13), 185. 



" Zeit. physiol. Chem., 1909 (58), 475. 



3* Morner," Skand. Arch. Physiol., 1889 (1), 210; Zcit. physiol. Chem., 1895 

 (20), 357, and 1897 (23), 311; Sciimiodeberg, Arch. exp. Path. u. Pharm., 1891 

 (28), 358. Hoc also Levene and La Forge, Jour. Biol. Chom., 1913 (15), 09 and 

 155; 1914 (18), 123. 



•••f' Biocliem. Zeit., 1910 (2G), 116. 



3« Pons, Arch, internat. physiol., 1909 (8), 393. 



