Structure‐function relationship of immunosuppressive drugs: A cautionary tale

Laurence A. Turka, Craig B. Thompson – 1 September 1991 – The immunosuppressants FK506 and rapamycin bind to the same immunophilin, FK506 binding protein (FKBP), and inhibit distinct signal transduction pathways in T lymphocytes. A nonnatural immunophilin ligand, 506BD, which contains only the common structural elements of FK506 and rapamycin, was synthesized and found to be a high‐affinity ligand of FKBP and a potent inhibitor of FKBP rotamase activity. Whereas 506BD does not interfere with T cell activation, it does block the immunosuppressive effects of both FK506 and rapamycin.

Vanadate inhibits glucose output from isolated perfused rat liver

Rafael Bruck, Haia Prigozin, Zipora Krepel, Paul Rotenberg, Yoram Shechter, Simon Bar‐Meir – 1 September 1991 – Previous studies have demonstrated that vanadate ions mimic many of the actions of insulin in in vitro systems. Also, vanadate administered to diabetic hyperglycemic rats lowers their blood glucose levels to normal values. In this study we demonstrate that vanadate inhibits glucose output in the isolated perfused rat liver. Glucose production was suppressed maximally (about 50% to 60%), on addition of extremely low vanadate ion concentrations (0.5 to 1 μmol/L).

Natural killer activity of human liver‐derived lymphocytes in various liver diseases

Kensaku Hata, David H. van Thiel, Ronald B. Herberman, Theresa L. Whiteside – 1 September 1991 – Liver‐derived lymphocytes were isolated from 40 human livers with end‐stage liver disease that were removed at the time of orthotopic liver transplantation. In addition, 10 resection specimens or whole livers removed from patients with liver cancer and seven normal livers (unused donor organs) were studied as controls. Liver‐derived lymphocytes were isolated from enzymatically digested tissue by gradient centrifugation and adherence to plastic.

Quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients

Hiroshi Imamura, Seiji Kawasaki, Junji Shiga, Yasutsugu Bandai, Kensho Sanjo, Yasuo Idezuki – 1 September 1991 – A simple morphometrical method was developed using a color image analyzing system, which allowed quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients. With this method, we estimated these values in 29 cirrhotic patients who underwent hepatic resection (nine cases) or nonshunting operation (20 cases).

Effect of insulin and plasma amino acid concentration on leucine metabolism in cirrhosis

Alexander S. Petrides, Livio Luzi, Adrian Reuben, Caroline Riely, Ralph A. Defronzo – 1 September 1991 – Clinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with 14Cleucine and indirect calorimetry.

An in situ hybridization, molecular biological and immunohistochemical study of hepatitis delta virus in woodchucks

Spyros Dourakis, Peter Karayiannis, Robert Goldin, Michael Taylor, John Monjardino, Howard C. Thomas – 1 September 1991 – The presence of hepatitis delta virus genomic RNA and hepatitis delta antigen was investigated in woodchuck liver and extrahepatic tissues by in situ hybridization using synthetic radiolabeled probes, Northern‐blot analysis and immunohistochemical staining for hepatitis delta antigen. Hepatitis D virus RNA and hepatitis delta antigen were detected in the nuclei of infected hepatocytes but in none of the other tissues examined.

Sodium retention and hepatic function after two‐thirds hepatectomy in the rat

Toshiyuki Ohno, Ramzi Sabra, Robert A. Branch – 1 September 1991 – Recently it was suggested that the onset of sodium retention in experimental cirrhosis in rats is related to a critical threshold of hepatic function, as assessed by the aminopyrine breath test. The aim of this study was to evaluate whether sodium retention occurred after two‐thirds hepatectomy in rats and to investigate the relationship between sodium retention and changes in hepatic function associated with liver regeneration in this model.

Histological and morphometrical indicators for a biopsy diagnosis of well‐differentiated hepatocellular carcinoma

Yoshinobu Nagato, Fukuo Kondo, Yoichiro Kondo, Masaaki Ebara, Masao Ohto – 1 September 1991 – Among 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions.

Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: An immunohistochemical study

Ruth Joplin, J. Gordon Lindsay, Stefan G. Hubscher, Gerald D. Johnson, Jean C. Shaw, Alastair J. Strain, James M. Neuberger – 1 September 1991 – The reason for the close association between primary biliary cirrhosis and the appearance of antibodies that recognize the E2 component of pyruvate dehydrogenase complex is not understood.

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