Low glutamine concentrations induce phenotypical and functional differentiation of U937 myelomonocytic cells.

L-Glutamine is the most abundant free amino acid of the human body and is essential for the culture of many cell types. Clinically, reduction of glutamine by administration of glutaminase or the use of glutamine analogs is a common therapy for patients with acute lymphocytic leukemia. In the current study, we investigated the influence of glutamine concentrations on the human myelomonocytic cell line U937. Decreasing the glutamine concentration evoked a reduction in DNA synthesis (R2 = 0.9885, P < 0.0001), increased cell volume (P < 0.01) and the cytoplasm/nuclear ratio, and enhanced the development of vacuoles but did not influence cell viability. Culturing cells in reduced concentrations of glutamine augmented the percentage of cells expressing CD64 (Fc receptor for IgG/FcgammaRI, P < 0.01), CD11b (complement receptor type 3/CR3, P < 0.001) and CD71 (transferrin receptor, P < 0.05). The percentage of U937 cells expressing CD23 (low affinity receptor for IgE/FcepsilonRII) was increased at low concentrations of glutamine at both the protein (P < 0.01) and mRNA levels. The percentage of U937 cells phagocytizing opsonized E. coli (P < 0.001) or latex particles (P < 0.001) was enhanced by lowering the glutamine concentration. In conclusion, reducing glutamine concentration causes differentiation of the cell line U937 along the monocytic pathway. These effects may indicate a mechanistic basis for prior published evidence that glutaminase and glutamine antagonists are effective anti-tumor agents.

Orthotopic liver transplantation in the management of end stage liver disease: the University of Vienna experience.

Two hundred and eight orthotopic liver transplantations (OLT) were performed in 191 patients at the I Department of Surgery, University of Vienna from 1982-1990. The most frequent indications were hepatocellular carcinoma, alcoholic cirrhosis, posthepatic cirrhosis, primary biliary cirrhosis, and fulminant hepatic failure. Patients with malignancy constituted 33.8% of cases. The overall results showed a 64% one-year and 58% two-year survival; best results were seen in patients with primary biliary cirrhosis and the poorest long-term results were in malignancy. There were 23 postoperative deaths (11%). Primary non-function was seen in 14 (7%) cases; acute rejection episodes were seen in 62% of patients. The presence of a well organised cadaver organ procurement system in eastern Austria with upto 41 donors per million population per year ensures that the 57% growth rate in OLT achieved in 1990 will be maintained with even better results.