Evidence for a Negative Feedback System Controlling Liver Regeneration 151 



showing well organized basophilic bodies, whereas cells in the middle and the 

 periphery of the lobules remained altered (Fig. 3). 



Confirming the earlier data of Harkness (8), we found that cell division 

 begins between 16 and 24 hours postoperatively in the periportal area. This 

 is significant because cells in this area remained altered for the longest time. 

 The changes in cytoplasmic ribonucleoprotein organization indicate an activa- 

 tion of the protein synthesizing mechanism of the liver cells after partial hepa- 

 tectomy, proceeding in a topographical pattern related to the direction of the 

 intralobular blood flow. According to the Law of Mass Action these changes 

 would be expected to appear with decreased protein concentration in the 

 immediate environment of these protein-secreting cells. The cells in the periphery 

 of the lobules would be expected to react faster and longer since the ones more 

 centrally located are in an environment richer in protein produced by the more 

 peripheral cells. This interpretation was, in part, verified experimentally by 



Fig. 4. Induction of cytoplasmic ribonucleoprotein 



changes in the liver by plasma dilution. 



A total of six male adult rats was used. 



Addition refers to a single intravenous injection of 5.5 ml of fluid. Replacement 



refers to a 5.5 ml single plasmapheresis treatment. All animals were sacrificed 



two hours after treatment. 

 Serum protein change refers to the percentage difference between the values 



obtained before treatment and those obtained at sacrifice. 



Liver ribonucleoprotein change refers to the disappearance of the basophilic 



bodies from the cytoplasm of the cells in the periportal area. 



showing that changes in the cytoplasmic ribonucleoprotein of the cells in the 

 periportal area appear rapidly after a sudden decrease of the serum protein 

 concentration (Fig. 4). After partial hepatectomy, however, these histochemical 

 changes occur as we have seen within thirty minutes before any appreciable 

 changes in the plasma proteins. 



The relationships between increased pressure in the portal system following 



