Current therapeutic relevance of liver gene transfer

Jean Michel Heard – 1 July 1994 – The liver represents a model organ for gene therapy. A method has been developed for hepatic gene transfer in vivo by the direct infusion of recombinant retroviral vectors into the portal vasculature, which results in the persistent expression of exogenous genes. To determine if these technologies are applicable for the treatment of hemophilia B patients, preclinical efficacy studies were done in a hemophilia B dog model.

The effect of increased hepatic sitosterol on the regulation of 3‐hydroxy‐3‐methylglutaryl—coenzyme a reductase and cholesterol 7α‐hydroxylase in the rat and sitosterolemic homozygotes

Sarah Shefer, Gerald Salen, John Bullock, Lien B. Nguyen, Gene C. Ness, Zhihong Vhao, Peter F. Belamarich, Indu Chowdhary, Susan Lerner, Ashok K. Batta, G. Stephen Tint – 1 July 1994 – We investigated hepatic cholesterol homeostasis in four homozygous sitosterolemic subjects from two unrelated families who showed enhanced absorption, diminished removal and increased tissue and plasma concentrations of sitosterol (24‐ethyl cholesterol).

Mitochondrial dysfunction during anoxia/reoxygenation injury of liver sinusoidal endothelial cells

Yuichi Fujii, Michael E. Johnson, Gregory J. Gores – 1 July 1994 – Sinusoidal endothelial cell injury plays a pivotal role in anoxia/reoxygenation liver damage. However, the mechanisms culminating in anoxia/reoxygenation endothelial cell injury remain unclear. Our aims were to determine whether anoxia/reoxygenation injury of sinusoidal endothelial cells causes mitochondrial dysfunction.

Bile acid inhibition of P‐glycoprotein–mediated transport in multidrug‐resistant cells and rat liver canalicular membrane vesicles

Roberto Mazzanti, Ornella Fantappié, Yukkio Kamimoto, Zenaida Gatmaitan, Paolo Gentilini, Irwin M. Arias – 1 July 1994 – To study the effect of bile acids on P‐glycoprotein–mediated drug transport, we performed experiments using multidrug resistant cells and rat canalicular membrane vesicles. Cellular accumulation and efflux of rhodamine 123 were measured in drug‐resistant cells by means of computerized quantitative image analysis and fluorescence microscopy.

Beneficial or adverse effects of hepatectomy vs. ethanol injection therapy in RBT‐1 carcinoma of the rat liver

Yasuharu Ikeda, Takashi Matsumata, Hiroshi Hayashi, Akinobu Taketomi, Kazuharu Yamamoto, Keizo Sugimachi – 1 July 1994 – In an attempt to ascertain the possible beneficial or adverse effects of ethanol injection into a hepatic malignant tumor, we carried out a series of experiments using the RBT‐1 carcinoma.

Timing of the first variceal hemorrhage in cirrhotic patients: Prospective evaluation of doppler flowmetry, endoscopy and clinical parameters

Sebastiano Siringo, Luigi Bolondi, Stefano Gaiani, Soccorsa Sofia, Gianni Zironi, Alessandra Rigamonti, Giulio Di Febo, Mario Miglioli, Giancarlo Cavalli, Luigi Barbara – 1 July 1994 – We followed 87 cirrhotic patients with esophageal varices and without previous hemorrhage for a mean period of 24 mo to prospectively evaluate the occurrence of variceal bleeding within (early) or after (late) 6 mo from entry and the contribution of portal Doppler ultrasound parameters to the prediction of early and late hemorrhage.

Favorable effects of total paracentesis on splanchnic hemodynamics in cirrhotic patients with tense ascites

Angelo Luca, Fausto Feu, Juan Carlos García‐Pagán, Wladimiro Jiménez, Vicente Arroyo, Jaime Bosch, Juan Rodés – 1 July 1994 – Total paracentesis is widely used in the treatment of patients with cirrhosis and tense ascites. However, very little information is available regarding its consequences on splanchnic circulation, and its effects on portocollateral blood flow have not been investigated.

Heterogeneity in hepatic transport of somatostatin analog octapeptides

Fricker, Valerie Dubost, Dietmar Schwab, Christian Bruns, Christoph Thiele – 1 July 1994 – Hepatic transport of the synthetic somatostatin analog octreotide—SMS 201–995, ‐Throl—and its novel derivative N‐α‐(α‐D‐glucosyl(1–4)‐1‐deoxy‐D‐fructosyl)‐octreotide—SDZ CO‐611, N‐α‐(α‐D‐glucosyl(1–4)‐1‐deoxy‐D‐fructosyl)‐‐Throl—was studied. In rats SMS 201–995 showed a plasma elimination half‐life of 1.2 ± 0.2 hr; that of SDZ CO‐611 was 1.9 ± 0.3 hours.

Skeletal muscle glycogen content in patients with cirrhosis

Oliver Selberg, Eva Radoch, Gerhard Franz Walter, Manfred James Müller – 1 July 1994 – We investigated stable cirrhotic patients for muscle glycogen content. Muscle biopsy samples were taken of 14 patients after overnight fasting. Electron microscopy showed normal intracellular distribution of glycogen (n=8). Muscle glycogen concentration was 16.5 ± 7.1 gm/kg wet muscle weight (normal range, 10 to 20 gm/kg).

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