XI. PATHOLOGY 495 



luivc succeeded in delerinining the fate of orally or pareuterall}' adminis- 

 tered Bi2 by employing cobalt GO-labeled B12 and measuring the radioac- 

 tivity in tissues, urine, and feces. They have emphasized the importance 

 of attempting to differentiate between true binding capacity from an in- 

 hibitory etTect on the microbiological test which may be exerted by certain 

 substances. Yeast nucleic acid, chondroitin sulfuric acid, and heparin, as 

 well as gastric juice and lysozyme, were shown to combine with B12 so as 

 to make the vitamin unavailable to the test organisms. They confirmed 

 the obser\ation of Bird and Hoevet-^ that the combination of Ij^sozyme and 

 Bi-j when subjected to dialysis underwent ready dissociation and almost all 

 tlie 15io was recoverable in the dialyzate. On the other hand, the complex 

 formed by gastric juice and B12 was stable under the experimental condi- 

 tions and yielded very little dialyzable B12. The recovery percentages of 

 B12 in the dialyzates when yeast nucleic acid, chondroitin sulfuric acid, 

 and heparin were employed as binding agents were intermediate between 

 the high value obtained with lysozyme and the minimum recovered in the 

 case of gastric juice. Chow and Davis, by measuring urinary and fecal 

 radioactivity, were also able to show that, in rats, absorption of cobalt GO- 

 labeled B12 was greater when the vitamin was administered by mouth in 

 combination with yeast nucleic acid than when it was given in the free 

 form. These observations are of great interest, but the authors' conclusion 

 that the techniques employed in their studies "... may result eventually 

 in the discovery of compounds with the therapeutic properties of Castle's 

 intrinsic factor" must be accepted with reservations, since the factors 

 which govern the absorption of B12 in the normal rat must differ vastly 

 from those which are operative in pernicious anemia. 



The radioactivity tracer technique has been applied by Heinle and as- 

 sociates^^ to the study of the absorption and excretion of Bjo in perni- 

 cious anemia. As a result of preliminary studies, these authors conclude 

 that the intrinsic factor probably "... functions by increasing the utiliza- 

 tion of orally administered vitamin B12, and that failure of utilization in 

 the absence of intrinsic factor is the result of failure of absorption." 



Ungley,^** while acknowledging that intrinsic factor is probably concerned 

 with absorption of B12, states: "It is unlikely, however, that the role of 

 Castle's intrinsic factor is confined to absorption." In support of the hy- 



^* B. F. Chow, Proc. Scient. Sessions 7th Ann. Meeting, Natl. Vitamin Found, p. 1 



(1952). 

 " B. F. Chow, C. Rosenblum, K. H. Silber, D. T. Woodbury, R. Yamamoto, and C. 



A. Lang, Proc. Soc. Exptl. Biol. Med. 76, 393 (1951). 

 28 O. D. Bird and B. Hoevet, J. Biol. Chem. 190, 181 (1951). 

 " R. W. Heinle, A. D. Welch, V. Scharf, G. C. Meacham, and W. II. Prusofif, Trans. 



Assoc. Am. Physicians 65, 214 (1952). 

 3" C. C. Ungley, Brit. J. Nutrition 6, 299 (1952). 



