Thomas S. Argyris

The stimulation of liver growth and demethylase activity following phenobarbital treatment

Summary Multiple subcutaneous injections of phenobarbital into rats result in an increase in drug-metabolizing activity of the liver, as measured by an increase in demethylase activity. After the cessation of phenobarbital treatment the demethylase activity returns to normal. Associated with the increase in demethylase activity is an increase in liver weight, total protein, and nuclear count. Hepatocyte proliferation precedes the measurable increase in the nuclear count. After the last injection of phenobarbital, liver weight, total protein, and nuclear count slowly return to normal levels, following closely the decrease in demethylase activity.

Additive effects of phenobarbital and high protein diet on liver growth in immature male rats

Abstract Feeding a high-protein diet to immature male rats results within 7 days in significant increases in liver weight and total liver protein. Daily subcutaneous injections of phenobarbital into immature male rats results in an increase in liver weight and total protein, compared to rats fed a 15% protein diet. Immature male rats given both a high-protein diet and injected with phenobarbital show additive increases in liver weight and total protein. The feeding of a high-protein diet, or the injection of phenobarbital each results in increases in hepatocyte mitotic activity in immature male rats. The simultaneous feeding of a high-protein diet and the injection of phenobarbital results in additive effects on hepatocyte mitotic activity. Associated with the increase in liver size and hepatocyte mitotic activity induced by the feeding of a high-protein diet is an increase in the specific activity of ornithine transcarbamylase, a urea cycle enzyme. Aminopyrine demethylase activity, a drug-metabolizing enzyme, is not increased. Marked increase in aminopyrine demethylase activity is however, associated with the increase in liver size produced by the injection of phenobarbital. Ornithine transcarbamylase activity is not increased after phenobarbital treatment. Marked increases in both aminopyrine demethylase and ornithine transcarbamylase activities are associated with the additive increase in liver size produced by the combined treatment with 64% protein diet and phenobarbital. These results suggest that there may be two separate growth compartments in the liver, one which responds to phenobarbital, and one to high-protein diet.

Stimulation of hair growth during skin regeneration

Abstract Wound healing in mice results in the stimulation of surrounding resting hair follicles to undergo normal growth and differentiation. This stimulation is first apparent microscopically about 7–8 days after injury and grossly at 12–15 days. Neither liver regeneration nor the growth of subcutaneously inoculated Ehrlich ascites tumor result in the stimulation of hair growth. It is concluded, therefore, that the stimulation of hair growth by regenerating skin may be organ specific. It has been possible to demonstrate that the stimulation of resting follicles is best associated with the hyperplastic epithelium situated between the resting hair follicles and the wound, and not with the initial tissue necrosis or fibroblastic proliferation. The results of this investigation are analogous to other studies which demonstrate the stimulation of one tissue by another, such as the stimulation of embryonic or adult tissues by tumors, and the stimulation of one tumor by another. It is suggested that in all such investigations three factors seem to be present, namely, necrosis, epithelial hyperplasia, and a competent target organ or tissue. What varies is the topographical location of each of these factors.

Stimulation of immature male rat liver growth by phenobarbital and 3-methylcholanthrene

Abstract Daily injections of 100 mg phenobarbital/kg body wt stimulate substantial increases in liver growth. However, after 5 days of treatment there is no further growth in response to phenobarbital. At this time, the liver still grows after a single injection of 20 mg of 3-methylcholanthrene/kg body wt. It is concluded that the two drugs stimulate liver growth by different mechanisms, as they do liver drug metabolizing enzyme activity. In addition, we have shown that 100 mg phenobarbital/kg body wt in the immature male rat stimulates liver growth by both hepatocyte hypertrophy and hyperplasia, while 20 mg 3-methylcholanthrene/kg body wt with or without phenobarbital pretreatment stimulates only cell hypertrophy. Neither drug significantly affects mitotic activity in littoral or bile duct cells.

On the mechanism of hair growth stimulation in wound healing.

Abstract Removal of a portion of the skin on the dorsum of mice without surgical intervention has been accomplished by allowing subcutaneously inoculated Ehrlich ascites tumor to invade and replace the overlying skin. Loss of a portion of the skin by this procedure does not result in the stimulation of growth of the surrounding resting hair follicles, as normally occurs after the surgical removal of a piece of skin. Evidence is presented that the lack of hair growth stimulation after loss of skin mass by tumor invasion is not due to the presence of the tumor affecting the competence of the resting hair follicles to respond to growth-promoting stimuli. We conclude that the loss of skin mass by itself, is not a sufficient stimulus for triggering the growth of resting hair follicles. Therefore it is suggested that hair growth stimulation in wound healing is due not to loss of skin mass, but probably to the release of a substance(s) from the wound. In mice of the same sex and age, bearing wounds of similar size and in a similar position, wide variations occur in the time of appearance, amount, rate, and pattern of hair growth stimulation. It is suggested that the variations in these parameters are due more to differences in the competence of the responding resting hair follicles than to differences in the amounts of substances released by the wounds.

Ribosome accumulation in 3-methylcholanthrene-induced liver growth in adult male rats

Abstract One injection of 20 mg/kg body weight of 3-methylcholanthrene results in liver growth, as evidenced by increases in liver wet weight, total protein, and total RNA. DNA does not increase. Total ribosomal RNA also accumulates, but changes in free and membrane-bound ribosome fractions are proportionately different from changes in total ribosomal RNA. Within 12 hr after injection, there is an increase in free ribosomal RNA which then decreases to control levels between 48 and 72 hr. In contrast, membrane-bound ribosomal RNA shows no immediate change, but between 48 and 72 hr the membrane-bound ribosomal RNA increases markedly above control levels, at the same time that free ribosomal RNA is decreasing to control levels. Thus, ribosomal RNA accumulation observed after 3-methylcholanthrene injection is not due to a coordinate increase in free and membrane-bound ribosomal RNA.