IX. EFFECTS f)F DKFICIENX'Y 187 



Cutilia el al."' foiiiul that, on a dirt, coiilaiiiiii^ 2(> % of "N'itainin-'l'cst 

 Casein" anil 2 % sult'asuxidinc no cHect of P(1A coiikl be olwerved on growth 

 rate. However, a normoeytic anemia develojXHl in which the hemof^lohin 

 content, was raised from 8.() g. to 14.4 g. % by the addition of 0.5 mg. of 

 Pd.V jK'r kilogram of diet. Refined liver extract containing the anti-perni- 

 cious anemia factor produced a smaller hemoglobin response. It seems 

 piobable that the diets employed were tleficient l)oth in POA and in vita- 

 min Bi2 . Crude casein in the amounts used in the diets constitutes a good 

 source of Bi2 . Since pigs have been shown to require B12 , it seems very 

 likely that these pigs which received vitamin-free casein were deficient 

 both in vitamin B12 and in PGA. 



Pteroylglutamic acid deficiency has also been induced in the pig by the 

 feeding of a crude "x methyl PGA" antagonist.^* This antagonist has the 

 advantage that its action can be completely reversed by pteroylglutamic 

 acid.'* The feeding of antagonist accentuates the anemia observed on a 

 purified diet containing sulfasuxidine. The anemia produced with the sul- 

 fonamide ration is normoeytic.''^ The hematological manifestations observed 

 with sulfasuxidine plus antagonist include (a) severe macrocytic anemia, 

 (b) leucopenia, with a greater proportional reduction of polymorphonu- 

 clear than of mononuclear cells, (c) mild thrombocytopenia, and (d) hyper- 

 plastic bone marrow with an increase in immature nucleated red cells which 

 resemble the megloblasts observed in pernicious anemia.''^ The blood and 

 bone marrow are rapidly restored to normal by the injection of 10 to 20 

 mg. of either PGA or the corresponding diglutamate, triglutamate, or 

 heptaglutamate. Thus, all the known conjugates appear active. .\ partial 

 response was given by injection of a single dose of 0.10 mg. of PGA which 

 produced a reticulocyte peak of 10 % and an increase in hematocrit read- 

 ing of 10 % in 9 days. With larger amounts of PGA, reticulocyte responses 

 varied between 1 1 and 42 % and there was a corresponding rapid increase 

 in the hematocrit value between 10 and 20 %. AVhen 1 unit (corresponding 

 to approximately 1 7 of vitamin B12) of U.S. P. injectable liver extract was 

 given per day, the blood and bone marrow^ changes were neither prevented 

 nor was their onset postponed. When used curatively, liver extract, 30 to 

 150 units total, and vitamin B12 , 150 7 total, produced some hemapoietic 

 response although less than that elicited by PGA. 



Thymine, which produces a hematological response in pernicious anemia, 

 was inactive; xanthopterin, tyrosine, adenine, and uracil were also ineffec- 

 tive. 



" T. J. Cuiiha, K . W. Colby, L. K. Bustad, and J. F. Bone, J. Nutrition 36, 215 (1948) . 

 '8 A. L. Franklin, E. L. R. Stokstad, M. Bolt, and T. H. Jukes, /. RioJ. Chem. 169, 



427 (1947). 

 "G. E. Cartwright, B. Tatting, H. A.shenbruckcr, and M. M. Wintrobe, Blood 4, 



301 (1949). 



