Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormal liver chemistries, unexplained fevers, or hepatomegaly prompted 36 liver biopsies on 34 patients with the acquired immunodeficiency syndrome. The most common finding was the presence of hepatic granulomas, seen in 13 of the biopsy specimens. Eight of these granulomas were ill-defined, and 5 were more clearly associated with mycobacterial disease. Portal fibrosis and fatty infiltration were common, but a paucity of significant inflammatory activity was seen despite elevated aspartate aminotransferase levels, perhaps related to the underlying immunoincompetent status. Other noteworthy histopathologic findings included 1 patient each with peliosis hepatis and cryptococcal hepatitis. Electron-microscopic evidence of cytoplasmic tubular structures or viral particles were seen within the hepatocytes of 2 patients. It is concluded that a broad spectrum of hepatic histopathology may be seen in the acquired immunodeficiency syndrome, and that liver biopsy may be diagnostically valuable in the clinical investigation of such patients.
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PMID:The spectrum of liver disease in the acquired immunodeficiency syndrome. 372 95

Acute hepatic ischaemia was induced in pigs by means of a portacaval shunt with hepatic artery ligation after 24 hours. Despite significant elevation in blood ammonia, fatty acids, aspartate aminotransferase, cerebrospinal fluid glutamine and ammonia, and brain tissue glutamine, ammonia and tryptophan, the experimental animals remained awake and alert and indistinguishable from sham-operated controls. The molar ratio of branched-chain to aromatic amino acids fell sharply in the arterial blood, but showed a terminal attempt at compensation in muscle venous samples. Portal and muscle venous insulin levels were elevated, and glucagon values rose in all circulation segments in the experimental group. The failure to induce coma in these pigs, despite the presence of many of the classical biochemical features, suggests that the syndrome of encephalopathy comprises several stages, and that the pig may be an important model in which to define these.
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PMID:Acute hepatic ischaemia in the pig- the changes in plasma hormones, amino acids and brain biochemistry. 725 Aug 93

Plasma glucagon and growth hormone concentrations were measured fasting and after oral glucose in 19 patients with portal vein block with extensive portal-systemic shunting but minimal liver cell damage, 11 cirrhotic patients and 12 matched control subjects. Portal vein block patients and controls had similar fasting glucose and glucagon levels (glucose 3.8 +/- 0.1 mmol/l VS control 3.4 +/- 0.1 mmol/l (mean +/- SEM); glucagon 57.5 +/- 9.1 pg/ml VS control 51.3 +/- 7.8 pg/ml). Cirrhotic patients were hyperglycaemic (cirrhosis 4.3 +/- 0.2 mmol/l VS control 3.4 +/- 0.1 mmol/l, p < 0.01) with significantly elevated glucagon levels (167.3 +/- 61.1 pg/ml VS control 51.3 +/- 7.8 pg/ml, p < 0.05), which suppressed towards control values after oral glucose. There was no correlation between fasting plasma glucagon levels and the degree of portal-systemic shunting in cirrhotic patients. There was a strong correlation between fasting plasma glucagon concentrations and aspartate transaminase levels (r = 0.68; p < 0.01) in cirrhotic and portal vein block patients. Significant elevations of growth hormone were seen only in cirrhotic patients. It is concluded that hyperglucagonaemia is a feature of hepatocellular damage rather than portal-systemic shunting but the relationship between elevated glucagon and growth hormone concentrations and carbohydrate intolerance in cirrhosis remains unclear.
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PMID:Hyperglucagonaemia in cirrhosis. Relationship to hepatocellular damage. 741 64

In this study, the possible role of the hepatic microcirculation in phalloidin-induced cholestasis and hepatotoxicity was examined in isolated perfused rat livers (IPRL). Administration of a phalloidin bolus (1 mg/kg body weight) through the portal vein induced an immediate reduction of bile flow. In 16.9 minutes, bile flow was 50% lower than basal values. Portal pressure was only increased in 60 minutes after phalloidin injection and increased sharply from this time up to the end of perfusion (90 minutes). Under these conditions, phalloidin did not induce liver cell cytolysis, as assessed by aspartate transaminase (AST) and lactate dehydrogenase (LDH) release in the perfusate effluent. Under electron microscopy, hepatocytic vacuolization was mild 15 minutes after phalloidin administration but increased with time. At the end of perfusion, the hepatic architecture was markedly altered; erythrocyte accumulation was observed in both sinusoids and hepatocyte vacuoles. Evaluation by multiple indicator dilution curves showed that extravascular volume (EVV) was significantly affected by phalloidin. It was augmented in 30 minutes after phalloidin administration with values increasing gradually over time. Neither vascular nor cellular volume was altered. The hepatic swelling may be attributed to enlargement of the extravascular space of the liver. These results indicate that changes in the liver microcirculation are not the primary cause of phalloidin-induced cholestasis in the IPRL.
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PMID:Effect of phalloidin on cholestasis, hemodynamics, and microcirculation in isolated perfused rat liver. 859 55

Hepatic cytokine gene expression is independently stimulated by circulating microbial products and reductions in the cellular O2 supply. Although these stimuli occur sequentially after gram-negative bacteremia, it is unknown whether their interplay augments production of interleukin (IL)-1 by the liver. We studied the effects of intraportal Escherichia coli (EC) bacteremia and secondary constant-flow hypoxia (Po2, approximately 46 Torr for 30 min) on IL-1 alpha and IL-1 beta gene expression in ex situ buffer-perfused rat livers over 180 min (n = 67). At t = 0, normoxic EC and normal saline (NS) controls received 10(9) live EC serotype 055:B5 and 0.9% NaCl, respectively; in livers subjected to EC+hypoxia-reoxygenation (H/R) and NS+H/R, hypoxia began 0.5 h after EC or NS and was followed by 120 min of reoxygenation. Portal and hepatic venous perfusates were serially analyzed for bacterial colony-forming units, O2 uptake, and aspartate aminotransferase. At 60 min (peak hypoxia) and 180 min, cDNAs for IL-1 alpha and IL-1 beta were hybridized to whole liver RNA, and IL-1 beta protein levels in venous perfusates were assessed. Intrahepatic levels of reduced glutathione (GSH) were measured as an index of oxidative stress. Compared with normoxic EC, IL-1 alpha transcripts decreased at 180 min in EC+H/R livers (P < 0.0001) as did IL-1 beta mRNA (P < 0.05), despite similar EC clearance, GSH levels, posthypoxic O2 uptake, and aspartate aminotransferase release. Hepatic secretion of IL-1 beta likewise fell in EC+H/R vs. EC controls (P < 0.005). Prostaglandin H synthase-2 (COX-2) message accumulation was not enhanced by H/R, and indomethacin did not reverse H/R-mediated suppression of IL-1 production. In contrast, H/R-related falls in EC-induced IL-1S expression were reversed by allopurinol or catalase. Thus brief hypoxic stress of the liver causing neither GSH depletion nor functional impairment downregulates postbacteremic IL-1 expression by a mechanism involving O2 radicals but not cyclooxygenase metabolites.
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PMID:Brief hypoxic stress downregulates E. coli-induced IL-1 alpha and IL-1 beta gene expression in perfused liver. 894 69

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.
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PMID:Effect of pre-reperfusion portal venous blood flush on early liver transplant function. 895 23

To assess the effect of partial portal arterialization on the remaining liver after usually lethal extended hepatectomy, 30 mongrel dogs underwent 84% partial hepatectomy and were divided into three groups as follows: group 1, 84% partial hepatectomy (n = 10); group 2, 84% partial hepatectomy and splenectomy (n = 10); group 3, 84% partial hepatectomy and splenectomy and splenic artery-vein (A-V) shunt (n = 10). Another five dogs were pre-operatively killed normal controls. Portal vein flow (PVF) decreased to about 60% in groups 1 and 2, but PVF in group 3 was maintained at the pre-operative level. Oxygen saturation of portal vein blood increased markedly, to between 83% (group 1) and 88% (group 3). Portal vein pressure (PVP) increased in groups 1 and 2 by 1.6 to 1.7 times the pre-operative value, but no significant difference in PVP, serum aspartate aminotransferase (AST) and arterial ketone body ratio was found between the three groups. Plasma endotoxin levels after 84% partial hepatectomy were significantly lower in group 3 than in groups 1 and 2. Both of hepatocellular and secretory protein synthesis were enhanced in group 3 compared with the other two groups. These results suggest that partial portal arterialization using a splenic A-V shunt might bring about a beneficial effect on remaining liver function after extended hepatectomy.
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PMID:Short-term effect of portal vein arterialization on hepatic protein synthesis and endotoxaemia after extended hepatectomy in dogs. 940 25

Although endotoxin exacerbates hepatic microcirculatory disturbance, little is known of the way in which it acts on the hepatic microcirculation. We measured endotoxin-induced changes in hepatic microcirculation and investigated the effect of endotoxin on hepatic microcirculation in rats. After male Wistar rats were anesthetized, a lobe of the liver was observed with an inverted intravital microscope. Erythrocytes (RBC) were labeled with fluorescein isothiocyanate (FITC) and injected. The flow velocity (FV) of FITC-RBC in sinusoids was measured with an off-line velocimeter. Portal pressure (PP) and mean arterial pressure (MAP) were measured with a catheter cannulated in the portal vein and the left carotid artery, respectively. After a small dose (1 mg/kg) of endotoxin had been administered intravenously, FV decreased and PP increased gradually after 30 min. MAP showed no significant change, except for an initial decrease. However, when 5 mg/kg of endotoxin was administered, FV and PP increased, with a peak at 10 min, which was not observed with the small dose. In the late phase, FV decreased and PP increased, as was seen with the small dose. Endotoxin increased serum aspartate aminotransferase and lactate dehydrogenase activities. These results suggest that endotoxin induces hepatic microcirculatory disturbance, which may cause liver injury.
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PMID:Effect of lipopolysaccharides on erythrocyte flow velocity in rat liver. 943 17

The role of nitric oxide (NO) on liver oxidative stress and tissue injury in rats subjected to tourniquet shock was investigated. This shock model differs from others in that injury is a consequence of remote organ damage. Liver oxidative stress becomes evident after hind limb reperfusion, as evidenced by the loss of total tissue thiols; by increases in tissue oxidized glutathione (GSSG), lipid peroxidation (LPO), plasma aminotransferases (alanine aminotransferase (ALT) and (aspartate aminotransferase (AST)), and plasma nitrites; and by a 36% loss in total superoxide dismutase (SOD) activity. Portal blood flow is reduced by 54.1% after 2 h of hind limb reperfusion. Inhibition of NO synthesis with Nomega-nitro-L-arginine methyl ester or L-arginine methyl ester increased mean arterial blood pressure; further reduced portal blood flow; and aggravated liver injury as assessed by further loss in total thiols, increased LPO and GSSG content, and further increases in plasma ALT and AST. Total plasma nitrites were lower than in control animals, and total tissue SOD activity decreased by more than 80%. Treatment with the NO donor sodium nitroprusside reverted the decrease in portal blood flow and also reverted tissue thiol loss, LPO, and GSSG increases, as well as the loss of ALT and AST to plasma and of SOD activity to levels comparable to untreated control shock animals. As expected, plasma nitrites were greater than in tourniquet control animals. These data support the hypothesis that endogenous NO formation protects the rat liver from the consequences of oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock.
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PMID:Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock. 961 80

Criteria for histologic diagnosis of chronic rejection (CR) are based on changes seen late in the disease process that are likely to be irreversible and unresponsive to treatment. Changes occurring during the evolution of CR are less clearly defined. The serial biopsy specimens, failed allografts, and biochemical profiles of 28 patients who underwent retransplantation for CR were examined with the aim of identifying histologic and biochemical features that were present during the early stages of CR. For each case, a point of acute deterioration in liver function tests (LFTs) was identified ("start time" [ST]) that subsequently progressed to graft failure. Biopsy specimens before, at the time of ("start biopsy" [SB]), and after the ST were assessed histologically, and findings were correlated with the biochemical changes. CR resulted from acute rejection (AR) that did not resolve. Centrilobular necroinflammation (CLNI) associated with an elevated aspartate transaminase (AST) level and portal tract features of AR were present at the start. Portal AR features resolved, CLNI persisted, AST level remained elevated, and bilirubin and alkaline phosphatase levels progressively increased throughout the evolution of CR. Portal tracts also showed a loss of small arterial and bile duct branches, with arterial loss occurring early and bile duct loss as a later progressive lesion. Foam cell arteriopathy was rarely seen in needle biopsy specimens. In conclusion, findings from this study may help identify patients at risk of progressing to graft loss from CR at a stage when the disease process is potentially reversible and amenable to treatment.
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PMID:Histologic and biochemical changes during the evolution of chronic rejection of liver allografts. 1187 Mar 79


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