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)

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.
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PMID:Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats. 163 55

Laminin, hyaluronic acid (HA), procollagen III amino-terminal propeptide (PIIINP), and procollagen I carboxy-terminal propeptide (PICP) concentrations were measured by radioimmunoassay or radiometric assay in sera from 21 patients with glycogen storage disease (GSD). Laminin was increased in 16 of 29 samples from the six children with GSD I, 25/43 from the seven with GSD III, and 3/19 from the eight with GSD IX; laminin correlated with serum aspartate aminotransferase and gamma-glutamyltransferase but not with serum triglycerides, cholesterol, lactate, or urate. HA was increased in 20% of samples from GSD I, 58% from GSD III, and in none from GSD IX; HA correlated with serum lactate and urate but not with liver function tests, serum cholesterol, or triglycerides. Serum PIIINP was increased in only eight samples and PICP in only one; children with poor linear growth had low PIIINP and PICP. Immunostaining studies of nine liver biopsies taken at diagnosis showed increased laminin and PIIINP staining in portal tracts, fibrous septa, and around sinusoids in periportal regions; children with a greater degree of immunostaining did not always show significantly higher values of serum laminin or PIIINP. We speculate that raised serum laminin may reflect fibrogenesis (but not necessarily established fibrosis) in response to tissue damage in GSD, raised HA may reflect disturbed sinusoidal endothelial cell function, and low PIIINP and PICP impaired somatic growth rather than intrahepatic pathology.
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PMID:Serum concentrations of extracellular matrix components: novel markers of metabolic control and hepatic pathology in glycogen storage disease? 191 39

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)
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PMID:Factors predictive of the response to interferon in patients with chronic hepatitis C. 796 8

For the assessment of graft viability, serum hyaluronic acid (HA) levels during porcine orthotopic liver transplantation were measured in two groups: group 1 (viable: n = 5) in which allografts were transplanted following a minimal cold (4 degrees C) preservation, and group 2 (nonviable: n = 4) in which allografts were transplanted after cold static storage (4 degrees C) for 24 h in University of Wisconsin solution. The changes in the HA levels reached a significant difference between the two groups at 30 min after reperfusion (P < 0.02). In group 1, all animals survived for over 4 days, while all animals in group 2 died within 24 h. The serum HA also demonstrated a significant correlation with prothrombin time, beta-glucuronidase, and aspartate aminotransferase at 120 min after reperfusion. These results suggest that the measurement of serum HA is a potentially effective index for evaluating hepatic allograft viability.
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PMID:Serum hyaluronic acid for the assessment of graft viability in porcine liver transplantation. 798 43

It is well recognized that current selection criteria used to assess liver grafts before implantation are inaccurate and correlate poorly with graft outcome. A bench or laboratory-based test that could indicate the extent of liver injury immediately before implantation would be a valuable adjunct to clinical assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels in the caval effluent after liver perfusion have been suggested as indicators of preservation injury. Our objective was to investigate the relevance of preserved liver effluent HA and CK-BB as a predictor of early graft function. Perfused liver effluent HA and CK-BB levels were measured. Graft function was measured in terms of peak serum aspartate transaminase and its level on day 5 postoperatively as well as peak bilirubin level and prothrombin time. The cold ischemia time (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB level, CIT, and graft function parameters. The study was conducted at The Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom. Fifty patients undergoing OLT were studied. HA level was measured in 50 patients and CK-BB level in 30 patients. The main outcome measures were graft function and graft outcome. The graft function data are grouped according to effluent HA levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below 400 micrograms/L and the remaining 37 (74%) were above this threshold. There were no significant differences between the groups for these indicators of graft function. There was no difference between the 2 groups for CIT. The overall median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of the total CK activity. In a multiple regression analysis with CK-BB activity as the dependent variable, there was no demonstrable numerical relationship to graft function. In a separate multiple regression analysis similar results were obtained for HA. We conclude that the level of HA or CK-BB levels should not be used in determining the suitability for implantation of a harvested hepatic allograft.
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PMID:Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury severity after cold ischemia? 827 99

The uptake of hyaluronic acid (HA) was used to assess preservation damage to sinusoidal endothelial cells (SEC) during cold storage and subsequent normothermic reperfusion of rat livers. After 8, 16, 24, and 48 h storage in University of Wisconsin (UW) solution, livers were gravity-flushed via the portal vein with a standard volume of cold UW solution containing 50 micrograms/l HA. The effluent was collected for analysis of HA, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). The mean uptake of HA at 0 h was 59.1% +/- 4.6% (mean +/- SEM). After 8 h of storage, HA uptake was similar (55.5% +/- 7.3%), whereas after 16 h of storage it was reduced to 34.7% +/- 5.8%. At 24 and 48 h of storage, no uptake of HA was found. In a second series of experiments, livers were stored in UW solution and subsequently reperfused for 90 min with a Krebs-Henseleit solution (37 degrees C) in a recirculating system containing 150 micrograms/l HA. Following 8 h of storage, 34.6% +/- 8.0% of the initial HA concentration was taken up from the perfusate. After 16 and 24 h of storage, no uptake of HA was found. The results of this study indicate that damage to SEC occurs progressively during storage, leading to zero uptake of HA by the rat livers at 24 h of cold ischemia time. Additional reperfusion injury to the SEC was demonstrated by the reduced ability of the SEC to take up HA following normothermic reperfusion. The uptake of exogenous HA in preserved livers, used as a tool to assess SEC injury, enables the detection of early preservation damage.
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PMID:Hyaluronic acid uptake in the assessment of sinusoidal endothelial cell damage after cold storage and normothermic reperfusion of rat livers. 887 86

Twelve porcine liver transplantations were performed to investigate whether serum hyaluronic acid (HA) serves as a marker of warm ischemic injury. Group 1 was a control without warm ischemia (n = 7), and pigs in Group 2 were sacrificed by intracardiac KCl injection 60 min before harvesting (n = 5). All pigs survived more than 4 days in Group 1. In Group 2, all died within 2 days due to graft failure. Arterial and hepatic venous glutamic-oxaloacetic transaminase (GOT) in Group 2 were higher after revascularization. However, there were no differences between the 2 groups in arterial and hepatic venous HA levels. HA clearance by the graft also showed no differences between the groups. Although GOT reflected the degree of warm ischemia, HA and its hepatic clearance were not influenced by warm ischemic damage. In conclusion, HA was not thought to serve as a marker of liver injury when the graft suffered from warm ischemia.
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PMID:Study of the changes of serum hyaluronic acid during porcine liver transplantation: influence of warm ischemia. 889 33

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.
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PMID:The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation. 890 Mar 13

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.
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PMID:The value of serial determination of MEGX and hyaluronic acid early after orthotopic liver transplantation. 891 65

Activated Kupffer cells (KC) have been implicated in the damage sustained by preserved liver grafts during ischemia and reperfusion. The aim of this study was to compare ischemia/reperfusion injury in preserved, KC-depleted rat livers and preserved control livers, with special regard to sinusoidal endothelial cell (SEC) injury. Wistar rats were injected with liposome-encapsulated dichloromethylene diphosphonate, 48 hr before hepatectomy, to eliminate KC, or were withheld this pretreatment (controls). Livers were flushed with cold University of Wisconsin solution and after 0, 8, 16, or 24 hr of storage at 4 degrees C, were reperfused in a recirculation system with 200 ml of oxygenated Krebs-Henseleit solution at 37 degrees C for 90 min. Damage to SEC was measured by the uptake of hyaluronic acid (HA) from the perfusate and release of purine nucleoside phosphorylase (PNP). Perfusate samples were, furthermore, analyzed for aspartate aminotransferase (AST) and tumor necrosis factor-alpha. Carbon particles were infused in the perfusate to determine the phagocytotic capacity of KC. Biopsies were taken for histological examination and sections were stained with ED2 monoclonal antibodies to confirm the absence of KC. After 90 min of reperfusion, immediately after cold flush (t0), the uptake of HA was 72.2+/-2.3% and 69.3+/-1.3% in KC-depleted livers and in control livers, respectively (n.s.). After 8 hr of storage, HA uptake was 21.6+/-4.5% and 34.6+/-8.0%, respectively (n.s.). After 16 and 24 hr of storage and reperfusion, no uptake of HA was found in either KC-depleted or control livers, indicating abolished SEC function. PNP activities in the perfusate were higher in control livers (after 8 and 24 hr of storage), presumably due to release from damaged KC. No difference was found in AST and no tumor necrosis factor-alpha was measured in the perfusates of normal and KC-depleted livers. Electron microscopic studies showed that after 8 and 24 hr of storage and reperfusion, KC were activated and were able to phagocytose colloidal carbon. Our conclusion was that the elimination of Kupffer cells did not result in reduction of ischemic and reperfusion damage in livers preserved up to 24 hr, as assessed in vitro by SEC uptake of HA, PNP release, and AST release.
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PMID:No attenuation of ischemic and reperfusion injury in Kupffer cell-depleted, cold-preserved rat livers. 903 38


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