120 HAROLD KOENIG 



first. In more severe intoxications, loss of neuronal function follows the stage 

 of neuronal irritation. Alterations in neuronal structure accompany the 

 neurologic disorder. RNA-containing structures, i.e., nucleoli and NissI 

 bodies, are conspicuously aflfected. The neuronopathy may be reversible or 

 may result in necrobiosis, depending on the severity of intoxication. Spongy 

 degeneration of white matter occurs later, probably caused by oligoden- 

 droglial disease. 



FO undergoes conversion to acid-soluble nucleotides and is incorporated 

 into RNA in the feline neuraxis. Indeed, anabolic con\ersion of the fiu- 

 orinated pyrimidines seems to be a requirement for the production of neural 

 dysfunction. A depletion of RNA and a depression in protein biosynthesis 

 appear later and are most marked in neurons that become inexcitable. Dis- 

 turbances in other metabolic spheres may e.xist, but have not been demon- 

 strated. Many points of similarity, both physiologic and pathologic, can be 

 discerned between the disorders described and some virus infections and 

 degenerative diseases of the nervous system. It seems possible, therefore, that 

 derangements in pyrimidine nucleotide or nucleic acid metabolism may be 

 present in some of the latter disorders. The fiuorinated pyrimidines are 

 useful tools for the production of focal neuronal disease. Their use may 

 provide experimental models for some of the degenerati\e neuronal diseases 

 that afflict man. 



References 



Harbcrs, E.. Chaudhuri, N. K.. and Heidtlberger, C. 1959. Studies in fluorinated 



pyrimidines: VIII. Further biochemical and metabolic investigations. /. Biol. 



Chem. 234, 1255-2162. 

 Henderson, J. F., and LePage, G. .\. 1958. Naturally occurring acid-soluble nucleotides. 



Chem. Revs. 58, 645-687. 

 Koenig, H. 1958a. Incorporation of adenine-8-C" and orotic-6-C" acid into nucleic 



acids of the feline neuraxis. Proc. Soc. Expl. Biol. Med. 97, 255-260. 

 Koenig, H. 1958b. An autoradiographic study of nucleic acid and protein turnover in 



the mammalian neuraxis. /. Biophys. Biochem. Cytol. 4, 785-792. 

 Koenig, H. 1958c. Production of injury to the feline central nervous system with a 



nucleic acid antimetabolite. Science 127, 1238-1239. 

 Koenig, H. 1960. Experimental myelopathy produced with a pyramidine analogue. 



A.M.A. Arch. Neurol, 2. 463-475. 

 Koenig, H. and Young, I. J. 1960. .Autoradiographic studies of nucleoprotein metab- 

 olism in the neuronopathy produced by a pyrimidine analog. Anat. Record 136, 



224. 

 Koenig, H., Gaines, D., Wells, W., Young, I. J., and Muniak, S. 1960a. Unpublished 



data. 

 Koenig, H., Young, I. J., and Kurth, L. E. 1960b. Unpublished data. 

 Krogh, E. v., and Bergeder, H. D. 1957. Experimental irradiation damage of the 



cerebellum demonstrated by gallocyanin-chromalum staining method. /" Cong. 



