Tissue inhibitor of metalloproteinase‐1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis

J P Iredale, R C Benyon, M J Arthur, W F Ferris, R Alcolado, P J Winwood, N Clark, G Murphy – 1 July 1996 – Liver fibrosis results from a relative imbalance between synthesis and degradation of matrix proteins. We have previously described release of the protein collagenase inhibitor, tissue inhibitor of metalloproteinase‐1 (TIMP‐1), by culture‐activated human hepatic stellate cells (HSCs). In this study, we have investigated the relative expression of TIMP‐1 and interstitial collagenase in culture‐activated rat HSCs and rat models of liver injury and fibrosis.

S‐adenosyl‐L‐methionine prevents disruption of canalicular function and pericanalicular cytoskeleton integrity caused by cyclosporin A in isolated rat hepatocyte couplets

I D Roman, G D Johnson, R Coleman – 1 July 1996 – Isolated rat hepatocyte couplets were used to study the effect of S‐adenosyl‐L methionine (SAMe) treatment on disruption of canalicular function caused by cyclosporin A (CyA). Canalicular function was assessed by counting the percentage of couplets that were able to accumulate the fluorescent cholephile choly‐lysyl‐fluorescein (CLF) into the canalicular vacuole between the two cells, i.e., canalicular vacuole accumulation (CVA).

Systemic hemodynamics and serum nitrate levels in patients undergoing endoscopic variceal ligation

M Yokoyama, H Shijo, K Ota, K Kubara, H Kokawa, T Kim, N Akiyoshi, M Okumura, K Inoue – 1 July 1996 – The effects of endoscopic variceal ligation (EVL) on systemic hemodynamics are unknown. This study was conducted to determine whether the obliteration of portal‐systemic collaterals by EVL affects systemic hemodynamics and serum nitrate concentrations in patients with compensated cirrhosis. We measured systemic and hepatic hemodynamics, azygos vein blood flow (AzBF), and serum nitrate concentrations before and immediately following EVL.

Improved sustained response following treatment of chronic hepatitis C by gradual reduction in the interferon dose

M L Shiffman, C M Hofmann, V A Luketic, A J Sanyal, M J Contos, A S Mills – 1 July 1996 – Interferon (IFN) treatment of chronic hepatitis C virus (HCV) is associated with a high rate of relapse. IFN is thought to exert its effect against HCV via direct viral inhibition and immune stimulation. We have hypothesized that relapse following termination of therapy results from the sudden withdrawal of this immune modulatory effect and that gradual reduction in the IFN dose may decrease the incidence of relapse.

Prolonged fecal excretion of hepatitis A virus in adult patients with hepatitis A as determined by polymerase chain reaction

H Yotsuyanagi, K Koike, K Yasuda, K Moriya, Y Shintani, H Fujie, K Kurokawa, S Iino – 1 July 1996 – In hepatitis A virus (HAV) infection, fecal excretion of the virus has been reported to cease shortly after symptoms occur. Although there have been several reports on detection of HAV in feces using polymerase chain reaction (PCR), the duration of fecal HAV shedding in human adult hepatitis A has not been well described. In the present study, we applied the reverse‐transcription (RT)‐PCR system to the detection of fecal HAV RNA in 10 patients with sporadic hepatitis A.

Reconstitution of bile acid transport in the rat hepatoma McArdle RH‐ 7777 cell line

E C Torchia, R J Shapiro, L B Agellon – 1 July 1996 – The liver recovers bile acids from the portal circulation primarily via an active process that is dependent on sodium ions. Hepatocytes lose the ability to transport bile acids in culture, and, in liver‐derived permanent cell lines, this ability is severely reduced or absent. To study the importance of bile acids in regulating liver‐specific functions (e.g., cellular bile acid and cholesterol metabolism), we have re‐established active bile acid transport in cultured cells.

L‐arginine minimizes reperfusion injury in a low‐flow, reflow model of liver perfusion

S M Jones, R G Thurman – 1 July 1996 – A low‐flow, reflow model of liver perfusion was used in the rat to investigate the effects of L‐arginine on reperfusion injury in the absence of blood elements. In contrast to in vivo studies, L‐arginine cannot minimize hypoxia by improving the microcirculation under these special conditions, but rather can only increase oxygen delivery upon reflow. During reflow, lactate dehydrogenase (LDH) release reached a new steady‐state value of 35 ± 3 U/g/h in livers perfused in the absence of L‐arginine.

Albumin but not fibrinogen synthesis correlates with galactose elimination capacity in patients with cirrhosis of the liver

P E Ballmer, J Reichen, M A McNurlan, A B Sterchi, S E Anderson, P J Garlick – 1 July 1996 – Albumin and fibrinogen synthesis rates were measured in 15 subjects with different clinical stages of postviral cirrhosis and compared with galactose elimination capacity and aminopyrin breath test. Forty‐three mg per kg body weight [2H5ring]phenylalanine with an isotopic enrichment of 10 atom% were intravenously injected. [2H5ring]phenylalanine enrichments in the plasma‐free phenylalanine and the albumin and fibrinogen isolates were measured by gas chromatography‐mass spectrometry.

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