Turpentine injection into rats elicits enhanced secretion of acute phase proteins inclucing cr,-macroglobulin (a2M). Hypophysectomized rats, however, do not respond in this way unless dexamethasone is given together with turpentine. On the other hand, dexamethasone injection alone did not result in an induction of cr,M synthesis. When a medium of Kupffer cell cultures was added to hepatocytes, a dose-dependent stimulation of u,M synthesis of up to 4-fold after l&l2 h was observed. However, the presence of low concentrations ( 10m9 M) of dexamethasone was essential for the stimulatory effect. We conclude that the acute phase induction of u,M in hepatocytes requires the synergistic action of glucocorticoids and a non-dialysable factor secreted by Kupffer cells.

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Abstract. A nephropathy with severe tubular atrophy was observed in Beagle dogs after oral administration of K2HP04 for 14 or 38 weeks. We describe the complete lysosomal degradation of atrophying tubular epithelial cells.During two experiments of 14 and 38 weeks duration, respectively, a total of 15 Beagle dogs received 0.8 g KnHPOJkg body weight daily with their food. All dogs were examined clinically at regular intervals. Renal biopsies were taken in the fourth week from beagles of the 14-week study. Results were compared with those of control dogs. At the end of the experiments the animals were killed and necropsies done. Different stains and histochemical reactions were applied to paraffin sections of the kidneys. Acid phosphatase and P-glucuronidase were found on cryostat sections. Kidneys futed by perfusion of five Beagles from the 38-week study and three Beagles of the 14-week study, and from five control dogs, were examined electron microscopically. Ultrahistochemically, acid phosphatase was demonstrated.Clinically, the dogs in both experiments vomited, were cachectic, and had elevated creatinine and blood urea nitrogen. Morphologically, qualitatively identical changes were seen, but the renal damage was most marked at 38 weeks. There were disseminated tubular atrophy (usually of the proximal tubules), focal scar tissue and nephrocalcinosis. The following pathogenesis was established for the lesions of the proximal tubule: Tubular atrophy begins with loss of differentiation of epithelial cells. Enzyme histochemistry, ultrahistochemistry and electron microscopy show an increase in autophagic vacuoles and autophagolysosomes. The lysosomal bodies showing fusion enclose large parts of the cytoplasm as the process continues. Complete lysosomal degradation of epithelial cells and extrusion of large lysosonies into the tubular lumen follow. After complete enzymatic digestion of the intratubular detritus, the residue is empty, convoluted and collapsed tubular basement membrane. Atrophic tubular epithelial cells have many organelle-free zones at their base, which contain fine filamentous material resembling that of the basement membrane.The degradation processes described here may explain why clinically the urinary sediment contains few cylinders and epithelial cells and why proteinuria decreases significantly toward 699

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