It was found that middle-sized molecules obtained from dialysate of uremic patients caused suppression of PHA-induced lymphocyte transformation. This was expressed by the lowering of labeled leucine incorporation and by the suppression of lymphocyte transformation as morphologically assessed. In view of the presented data middle-sized molecules seem to be biologically active substances.

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By measuring the incorporation of 14C-DL-leucine a decreased capacity of isolated perfused steptozotocin diabetic rat liver to synthetize plasma total proteins, albumin and the seromucoid fraction was found as compared with a control. The relative rate of synthesis of the seromucoid proteins calculated as proportional to the rate of synthesis of albumin or the total plasma proteins was approximately twice as great as in control liver. 14C-DL-leucine was also incorporated in perfused liver into the nonprotein but non-dialysable sugar-peptide fraction but the synthesis of the glycopeptide components of this fraction was markedly reduced in diabetic rat liver.

To investigate further the biologic activity of solutes in the middle-molecular-weight range, we studied the influence of these compounds on the migration of unseparated white blood cells and separated granulocytes and lymphocytes. Middle molecules (MM) inhibit the migration of unseparated leukocytes, but this effect on lymphocytes was seldom observed. With scanning electron microscopy, unseparated leukocytes were shown to adhere to one another, forming cellular clumps. This phenomenon could not be seen when separated cells were used. These results give some insight into the mechanism of inhibition exerted by MM and into the changes, observed in earlier experiments, of cellular composition of skin exudate obtained from untreated patients with uremia.