84 HISTOLOGY OF THE P( )IS( ),\-( ILAXDS OF BUFO AGUA. 



along and the gland may very rarely push ahead of it a small portion of the stratum eom- 

 pactum of the skin for a short distance which, however, it generally penetrates. 



The structure of the young glands is, except for the glandular epithelium, exactly 

 similar to that of the mature forms (figs. 4, o, and 6). The gland-collar is not as long as 

 in the adult state and the radial zones of epithelium have a thickness of but one cell each 

 (fig. 6). The epithelium of the youngest gland is flattened cuboidal in type (fig. 5). the 

 nucleus of each cell being close against the matrix of the gland-wall. The nuclei are oval 

 in shape, stain very deeply, and have a dense chromatin network with many small chro- 

 matic knots. There is usually one large chromatic mass, probably a nucleolus. We have 

 never seen one of these nuclei in mitosis, although cell division must occur and be fairly 

 rapid during the growth of these glands. As the glands begin to push downward into the 

 cut is, certain changes appear in the epithelial lining of the young acinus (figs. 4 and 5). 

 I'sually these changes do not occur simultaneously in all the cells of the gland, but rather 

 the cells develop individually or in small groups of two or three. The cell which is coming 

 to maturity and functioning enlarges tremendously, so that it may almost bridge the entire 

 cavity of the gland acinus, and the once clear homogeneous protoplasm becomes reticulated, 

 the reticular appearance being first noticeable at the cytoplasmic pole of the cell. The 

 cells begin to show large numbers of small vacuoles; then the cytoplasm of these swollen 

 cells begins to show large numbers of granules similar to the grains in the secretion of the 

 mature gland, the granules being more dense in the inner part of the cell; soon the entire 

 plasm seems to be converted into a mass of granules. While these eytoplasmic changes are 

 going forward, the cells increase in height more and more, until they are very long columnar 

 elements which gradually stream away into the acinus to form the granular secretion. 

 These changes, as we have said, do not occur simultaneously in all the gland-cells. The 

 first cells to show them are in the bottom or fundus of the acinus, those of the epithelium 

 (near the junction of the acinus with the collar) being the last to be transformed into 

 secretion. By the time that the gland has forced its way into the inner loose connective 

 tissue layer of the corium all the epithelial cytoplasm has disappeared and the gland is 

 lined only by the naked nuclei. 



Such a gland can be distinguished in two ways from the mature poison-sac which repre- 

 sents the adult gland: it is smaller in size and it shows no reaction to eliminates. Where, 

 then, does the epinephrin content of the glandular venom come from? It is found only in 

 the poison-glands when the gland reaches its full size. It is not found in any part of the 

 young glands; the glandular epithelium never gives the chromaffin reaction, which is nega- 

 tive also in the small skin glands which have been classed as producers of mucus. 



We must consider two possible methods of origin for this substance; first, an exogenous 

 one, that the epinephrin is produced by the well-known chromaffin organs, the adienal 

 gland, etc., and carried to the poison-sacs via the blood or lymph. Against this hypothesis 

 is the fact that we have no really reliable evidence of the presence of adrenalin in the general 

 circulation of any animal. It is, of course, unlikely that so great an amount of epine- 

 phrin could be transported as such in the circulating fluid of the body, since the intravenous 

 exhibition of a large amount of adrenin is in all animals productive of immediate death, and 

 Abel and Maeht have shown that the toad, while immune to bufagin, presents no such power 

 of resistance against his ow r n adrenalin. On the other hand, it is conceivable that the 

 compound might be transported to the gland in the form of some mother substance and 

 activated in the gland to form true epinephrin. 



More probably the entire process of adrenalin synthesis is the work of the poison-gland 

 itself and we can hypothesize the synthetic process as follows: During the destruction of 



