Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.
 ...
PMID:Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. 163 55

Physical, biochemical, and cytologic properties of synovial fluid from normal equine tarsal joints were investigated. Tarsal synovial fluid was pale yellow, clear, free of flocculent material, and did not clot. Volume varied in direct proportion to individual tarsal joint size. Relative viscosity was related to volume, polymerization and quantity of hyaluronic acid, and protein concentration. Mucinous precipitate quality (hyaluronic acid polymerization) was uniformly high. Results of certain analyses of serum were compared with those of tarsal synovial fluid. Tarsal synovial fluid protein concentration was low in conjunction with a high A:G ratio. Serum: synovial fluid sugar ratio was 1.24:1. Serum ALP, ACP, LDH, GOT, and GPT activity levels were higher than their corresponding levels of activity in tarsal synovial fluid. Serum ALD activity level was slightly lower than its tarsal synovial fluid counterpart. Total erythrocyte counts ranged markedly, while total leukocyte counts were uniform and low. Lymphocytes were the predominant synovial fluid cell type.
 ...
PMID:Characteristics of normal equine tarsal synovial fluid. 422 34

Lipiodolization--selective regional cancer chemotherapy using Lipiodol plus an anticancer drug (LPD)--can prolong survival time of patients with an unresectable hepatocellular carcinoma (HCC). To enhance understanding of LPD's influence on the cirrhotic liver, we carried out related studies. Forty-three cirrhotic patients with HCC were treated with LPD (epirubicin in a dose of 15-40 mg/m2 and Lipiodol of 0.02-0.25 ml/kg). Seven cirrhotic patients with HCC were subjected to hepatic angiography alone, and these subjects selected randomly served as controls. Among the 43 treated with LPD, 23 belonged to Child's class A, 15 to class B, and 5 to class C. Blood samples were taken before angiography (pre) and at 24 hours after angiography (post) from each patient. Post/pre ratio of the following parameters were compared between patients of the two groups: sGOT, sGPT, and LDH as a marker for hepatocyte injury; t. bilirubin and hepaplastin test (HPT) as hepatocyte function; alkaline phosphatase and gamma-GTP to examine bile duct injury; and serum hyaluronic acid level to determine an endothelial cell functions. Post/pre ratio of serum GOT, GPT, LDH levels, and HPT in patients treated with vs. without LPD were 1.32 +/- 0.59 vs. 0.92 +/- 0.09 (P < 0.001), 1.18 +/- 0.43 vs. 0.88 +/- 0.09 (P < 0.001), 1.11 +/- 0.20 vs. 1.00 +/- 0.07 (P < 0.05), and 0.95 +/- 0.10 vs. 1.09 +/- 0.12 (P < 0.01), respectively. There were no significant differences in post/pre LPD ratio of other parameters, rates of complications, and hospital stay after LPD for patients with Child's class A, B, and C. Hepatocytes are apparently the primary site of injury in cases of LPD. LPDs, using epirubicin in a dose of 15-40 mg/m2 and Lipiodol in a dose of 0.02-0.25 ml/kg, proved to be safe for cirrhotic patients with HCC.
 ...
PMID:Influence of lipiodolization on a cirrhotic liver. 772 71

Factors predictive of the response to interferon in patients with chronic hepatitis C remain to be identified. In this study, we investigated factors predictive of the short-term response, defined as a return to normal alanine aminotransferase activity after treatment, and the long-term response defined as normal alanine aminotransferase activity 1 year after completing treatment, in 75 patients with chronic hepatitis C virus treated with recombinant alpha interferon (either 6 MU x 3/week for 3 months then 3 MU x 3/week for 3 months (n = 27) or 3 MU x 3/week for 6 months (n = 48)). At the end of treatment, 42 patients (56%) had normal alanine aminotransferase activity ("responders") and 33 (44%) had high alanine aminotransferase activity ("non-responders"). Twenty (48%) of the 42 responders had normal alanine aminotransferase activity 1 year after treatment ("sustained responders"), while 22 (52%) had high alanine aminotransferase activity ("transient responders"). The dosage of interferon was not predictive of the short-term and the long-term response to treatment. The responders differed significantly from the non-responders in terms of age, i.v. drug abuse, aspartate aminotransferase, gammaglutamyltranspeptidase and alkaline phosphatase activities, bilirubinemia, serum bile acid concentrations, prothrombin time, platelet count, ferritinemia, hyaluronic acid levels, positivity for the antibody to 5.1.1 of the recombinant immunoblot assay band and the histological fibrosis score. The following parameters were independently correlated with the short-term response in a multivariate analysis: gammaglutamyltranspeptidase activity, serum bile acid concentrations and positivity for the antibody to 5.1.1 of the recombinant immunoblot assay band.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Factors predictive of the response to interferon in patients with chronic hepatitis C. 796 8

The onset of warm ischemia and reperfusion injury in the liver was investigated in a canine model through changes in parenchymal markers [isozyme class V of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT)], endothelial markers [purine nucleoside phosphorylase (PNP) and hyaluronic acid clearance], and the liver metabolism (ketone body ratio) in warm ischemia induced by inflow occlusion using Pringle's maneuver and subsequent reperfusion. In this in vivo model, a PNP assay system and a model were designed so as to exclude the influence of wide localization of PNP possibly originating in erythrocytes or the intestine, and to discriminate between PNP of endothelial cells and that of parenchymal cells in the liver. After 45 min of warm ischemia, reperfusion resulted in damage only to endothelial cells, as seen by significant increase in PNP alone (3.6 +/- 0.1 U/liter at the end of warm ischemia to 6.8 +/- 0.5 U/liter at 5 min after reperfusion, P < 0.01) and significant decrease in hyaluronic acid clearance compared to the 30-min warm ischemia group in which no increase in either marker for parenchymal and endothelial cells was noted. By contrast, after 60 min of warm ischemia, reperfusion resulted in damage to parenchymal cells along with damage to endothelial cells, as seen by significant increases in LDH(V) and ALT (93 +/- 4 U/liter and 32 +/- 2 IU/liter at the end of warm ischemia to 239 +/- 17 U/liter and 165 +/- 27 IU/liter at 5 min after reperfusion, respectively), as well as a marked increase in PNP and deterioration of hyaluronic acid clearance compared to the 45-min warm ischemia group. Reperfusion after 120 min of warm ischemia did not show recovery of metabolic function of the liver as evaluated by hepatic mitochondrial redox state. It is suggested that a time lag occurs in the onset of injury between parenchymal cells and endothelial cells and that endothelial cells are temporally earlier in failing than parenchymal cells when the liver is exposed to short-term warm ischemia and subsequent reperfusion.
 ...
PMID:Difference in onset of warm ischemia and reperfusion injury between parenchymal and endothelial cells of the liver. Evaluation by purine nucleoside phosphorylase and hyaluronic acid. 860 98

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.
 ...
PMID:The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation. 890 Mar 13

The efficacy of colchicine combined with ursodeoxycholic acid (UDCA) and UDCA alone in the treatment of patients with nonadvanced primary biliary cirrhosis (PBC) was evaluated in a 2-year controlled study. Seventy-four patients with PBC who had been treated previously with UDCA (at least 8 months) but still had abnormal liver test results, especially elevated alkaline phosphatase activity, were randomized to be administered colchicine (1 mg/d, 5 days per week) (n = 37) or a placebo (n = 37). In addition, the patients were treated with UDCA (13-15 mg x kg(-1) x day(-1)). The patients underwent clinical examination and liver tests every 6 months and upper endoscopy and liver biopsy at entry and at 2 years. Procollagen type III aminoterminal peptide (PIIINP), hyaluronic acid, and sulfobromophthalein (BSP) elimination kinetics were determined at entry and after 2 years. After 2 years of treatment, relative to UDCA, colchicine combined with UDCA did not significantly improve symptoms, laboratory findings (serum bilirubin level, alkaline phosphatase and alanine transaminase [ALT] activities, immunoglobulin [Ig] M level), serum markers of fibrosis, or histological features, except lobular inflammation. Colchicine did tend to slightly reduce the progression of esophageal varices; however, the difference was not significant. BSP elimination kinetics (45-minute retention percentage) was significantly improved when treated with colchicine. During the 2-year study, the only clinical complications were variceal bleeding in one patient administered colchicine and two administered the placebo. Two patients died from nonliver causes. One severe adverse effect (peripheral neuromyopathy) was observed in a colchicine-treated patient. In conclusion, this study suggests that colchicine appears to provide a slight advantage relative to UDCA alone in patients with nonadvanced PBC.
 ...
PMID:A randomized trial comparing colchicine and ursodeoxycholic acid combination to ursodeoxycholic acid in primary biliary cirrhosis. UDCA-PBC Study Group. 890 82

Post-transplant assessment of early graft function has become an essential part of monitoring, especially when deciding on retransplantation. If primary non-function is indicated, retransplantation is inevitable; early graft dysfunction may be related to subsequent complications. In a prospective study in 84 patients after orthotopic liver transplantation (OLT) we measured aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), bilirubin (BIL), prothrombin time, MEGX formation, hyaluronic acid (HA) and soluble interleukin-2 receptor (sIL-2R) concentrations during the first 2 postoperative weeks; graft outcome was followed over 4 months. The aim of this study was to determine whether graft survival could be predicted by such variables early after OLT. Compared with patients with stable graft function (n = 25), patients with post-transplant icteric cholestasis (n = 30) exhibited no difference in graft survival, despite a decrease in MEGX formation to a nadir median of 12 micrograms L-1 on day 10. Patients with rejection (n = 8) and septicaemia (n = 6) showed a marked decrease in MEGX values and an increase in HA and sIL-2R concentrations between postoperative days 3 and 7. Patients with primary non-function (PNF; n = 5) were characterized by strongly reduced MEGX formation (median 4 micrograms L) and increased HA values (median 2300 micrograms L-1) on day 3 after OLT. A total of 24/84 grafts were lost within 120 days. In a survival analysis using the Cox proportional hazards regression, HA and MEGX values on day 1 were the only independent variables entering the model that showed an adequate prognostic sensitivity. At cut-off points of 22 micrograms L-1 (MEGX) and 730 micrograms L-1 (HA) the combined use of these parameters in a parallel approach yielded a sensitivity of 58% with a corresponding specificity of 95% for 120-day graft survival. These findings suggest that the inclusion of MEGX and HA in postoperative monitoring of OLT patients may be helpful in the early prediction of graft survival.
 ...
PMID:The value of serial determination of MEGX and hyaluronic acid early after orthotopic liver transplantation. 891 65

Basic fibroblast growth factor (FGF) is thought to be involved in carcinogenesis and, to clarify its clinical significance, the study of its blood level in cancer patients is important. Plasma levels of basic FGF are reported to be elevated in some cancers. However, little is known of basic FGF levels in plasma in hepatocellular carcinoma (HCC). In this study, we measured basic FGF plasma levels in patients with chronic liver disease and compared the levels in chronic hepatitis (CH), liver cirrhosis (LC), and HCC. We also examined whether these levels were related to serum levels of asparate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, leucine aminopeptidase, total bilirubin, total protein, and albumin, and to the indocyanine green test (i.e., liver function tests) and to type III procollagen. 7S domain of IV type collagen, and hyaluronic acid (i.e., markers of liver fibrosis). Levels of basic FGF, determined by a quantitative "sandwich" enzyme immunoassay, were significantly elevated with the progression of liver disease; being 3.67 +/- 2.37 (mean +/- SD). 7.78 +/- 6.61, and 12.37 +/- 7.67 pg/ml in the CH, LC, and HCC groups, respectively. FGF levels were elevated to a greater extent in the HCC patients than in the CH (P < 0.0001) and LC patients (P = 0.0117). Levels were higher in LC than in CH (P = 0.0204). None of the liver function test findings or levels of markers of liver fibrosis were correlated with levels of basic FGF. These results suggest that circulating basic FGF could serve as a new indicator of the progression of chronic liver disease. The extremely elevated plasma of level basic FGF in the HCC group suggests that basic FGF may be related to the development of HCC.
 ...
PMID:Plasma level of basic fibroblast growth factor increases with progression of chronic liver disease. 905 7

To clarify the mechanism of hyperbilirubinemia in the setting of a left ventricular assist device (LVAD), the change in hepatocellular function, hepatic sinusoid endothelial microcirculation, and inflammatory response before and after LVAD implantation were evaluated. Eight consecutive patients underwent the placement of an LVAD, and serum levels of total bilirubin (TB), transaminases [alanine transaminase (ALT), aspartate transaminase (AST)], interleukin (IL-6, IL-8), and hyaluronic acid (HA), an indicator of hepatic sinusoidal circulation, were measured before and after LVAD implantation. The TB of all patients increased significantly in the first post operative week (p < 0.05 vs. pre-operatively). In five patients, the elevated TB (4.6 +/- 4.1 mg/dl) returned to pre-operative levels (2.7 +/- 2.0 mg/dl) by the 14th post operative day (Group R), but in the other three patients who died of multiple organ failure, the level of TB increased to 39.9 +/- 16.4 mg/dl (Group A). Levels of HA and IL-8 had good correlation with the level of TB (HA: r = 0.60, p < 0.05; IL-8: r = 0.55, p < 0.05). However, AST, ALT, and IL-6 were not related to changes in TB. These results suggest that hepatic sinusoid endothelial dysfunction and inflammatory reaction may play a significant role in hepatic failure in patients following implantation of an LVAD.
 ...
PMID:Hepatic sinusoid endothelial dysfunction plays a role in hyperbilirubinemia in patients following implantation of an LVAD. 936 82


1 2 3 4 5 6 7 8 9 10 Next >>