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)

Pseudoisocytidine (psi ICyd) is a C-nucleoside with enhanced stability and resistance to enzymatic deamination when compared to 5-azacytidine and 1-beta-D-arabinofuranosylcytosine. Elimination kinetics in plasma using [14C]psi ICyd showed a beta-phase for t1/2 for 14C of 2 hr and a beta-phase t1/2 of unchanged psi ICyd of 1.5 hr. Net recovery of radioactivity in urine over 24 hr varied between 40 and 80% of the administered dose; 50 to 90% was unchanged drug and the rest was pseudouridine. Human leukemic cells in vitro deaminated psi ICyd very slowly, formed appreciable quantities of pseudoisocytidine triphosphate, and incorporated small amounts into RNA and DNA. Clinical trials were done using a daily i.v. injection for 5 consecutive days. Hematological or intestine toxicities were not seen, nor was depression of white blood cell count observed in leukemic patients. Hepatic toxicity proved to be dose limiting; this was characterized by an early phase with elevation of prothrombin time and aspartate aminotransferase. A later phase with cirrhosis was observed in two patients. Autopsy showed massive hepatic necrosis in patients dying of acute toxicity and micronodular cirrhosis in one patient dying with the chronic form.
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PMID:Biochemical, pharmacological, and phase I clinical evaluation of pseudoisocytidine. 747 Oct 64

Frozen section examination was performed on 385 donor livers before transplantation. Exclusion criteria were applied to the donor livers examined to exclude potentially dysfunctional livers. The exclusion criteria included the following: severe macrovesicular steatosis, ischemic necrosis, prominent chronic portal inflammation, prominent periductular fibrosis, granulomatous inflammation, bridging fibrosis, and malignancy. Twenty-seven of the 385 donor livers examined were excluded before transplantation. The following histologic features were present in the excluded livers: severe steatosis (22), ischemic necrosis (2), portal inflammation (1), and periductular fibrosis (2). Steatosis was present in 51 of the 385 (13.25%) organs examined, including 22 of the donor organs excluded before transplantation. Twenty-nine livers with mild to moderate steatosis were implanted into size and blood type-matched recipients. Indicators of allograft function (prothrombin time and bilirubin) and damage (aspartate aminotransferase and alanine aminotransferase) were measured daily for the first 10 days after transplant. There was no statistically significant difference between the group of nonfat livers and donor livers containing mild steatosis. Statistically significant higher posttransplant serum alanine aminotransferase and prothrombin time levels were present in the patients with livers implanted with mild versus moderate steatosis. The 1-year survival rate for patients receiving fatty versus nonfatty donor livers was not statistically different (Kaplan-Meier, P = 0.592). No significant differences were found in the clinical and laboratory characteristics of donors whose organs were implanted compared with the clinical and laboratory characteristics of donors whose organs were excluded. The primary nonfunction rate after applying the exclusion criteria was 1.4%, which is a significant decrease compared with our primary nonfunction rate of 8.5% before using frozen section examination. Frozen section examination is useful in excluding donor organs which may become dysfunctional after transplantation.
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PMID:Frozen section evaluation of donor livers before transplantation. 750 53

Inherited and acquired disorders of the liver are attractive targets for gene therapy. Hepatic cells are susceptible targets for shuttle vectors because of a diversity of protein and viral receptors and accessibility of a selective afferent blood supply. Preservation of existing hepatic cell integrity and metabolic function is of paramount importance for successful whole animal gene therapy trials. In this report, we examine hepatic cell function and integrity following adenovirus-mediated reporter gene transfer to the liver in vivo. E1-deleted, replication-defective adenovectors encoding the LacZ gene driven by the human CMV promoter were delivered to the liver by isolated portal perfusion. The gene transfer rate, as determined by specific histochemical staining, approached 30% with recombinant protein detectable by Western blot throughout the course of study. Hepatic cell integrity as assessed by histology and hepatic enzyme profile (serum aspartate aminotransferase, gamma-glutamyl transpeptidase) demonstrated normal cellular architecture and no significant difference between transfected liver and controls. Hepatic synthetic and metabolic function, as determined by albumin levels, prothrombin time, and bilirubin, were similar between the two study groups. This study demonstrates that efficient adenovirus-mediated gene transfer and expression in the rat liver do not compromise hepatic cell metabolism and integrity.
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PMID:Hepatic function is preserved following liver-directed, adenovirus-mediated gene transfer. 754 33

A 26-year-old female patient with fulminant hepatic failure and a history of autoimmune hepatitis was heterotopically transplanted with a pig hepatic xenograft to provide temporary metabolic support prior to transplantation with a human donor organ. Circulating natural antipig antibodies were removed prior to transplantation by plasmapheresis and ex vivo en bloc perfusion of the donor pig kidneys. The liver xenograft functioned after transplantation as measured by active bile production, stabilization of prothrombin levels, and reduction in the circulating levels of lactic acid and the enzymes AST and ALT. Despite the removal of greater than 90% of the recipient's natural xenoantibodies prior to transplantation, the levels of antibody rapidly returned and were associated with antibody and complement-mediated rejection of the donor graft. Immunohistochemical evidence of graft rejection could be detected by the deposition of antibody, complement components including properdin, and endothelial swelling as early as 3 hr posttransplantation. These lesions progressed in severity and were accompanied by evidence of thrombosis and ischemic necrosis of the liver xenograft by 34 hrs posttransplantation. The main portal vein, hepatic artery, and vena cava were patent. The placement of the liver graft did not result in any improvement in the neurological status of the patient and she died 34 hr after xenografting due to irreversible brain damage. The information derived from this case has renewed interest in the clinical use of bioartificial devices and whole organ perfusion using xenogeneic tissue for temporary bridging of patients prior to allografting.
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PMID:The use of a pig liver xenograft for temporary support of a patient with fulminant hepatic failure. 760 34

Problems with the assessment of organ damage caused by toxic substances in places of residence have recently appeared with increasing frequency. In spite of this there have been so far no uniform, objective research methods which could allow their accurate evaluation. This is why the attempt has been made to assess morphological and functional condition of the liver in patients chronically exposed to mercury compounds in the place of settlement. The research group consisted of 62 patients exposed to metallic mercury at a yearly rate exceeding 24 kg for average duration of 16 years. Patients with the liver or biliary tract diseases, symptoms of chronic circulatory insufficiency, Australia (HBs+) antigen carriers and alcoholics were excluded from the research group. The control group consisted of 29 males. AST and ALT activity, prothrombin level, bilirubin and protein concentration in blood serum were measured and scintigraphic and USG examinations of the liver were performed. Mercury concentrations were also established. Scintigraphic examination yielded an abnormal image of the liver in 52% of the exposed patients. The differences in frequency and intensity of scintigraphic changes in comparison with the control group were of statistical significance. No pathological changes were found in USG examination. Significantly higher ALT activity and bilirubin concentration and significantly lower total protein concentration were found in the exposed group. The correlation between the intensity of scintigraphic changes and mercury concentration were noted. Liver scintigraphic examination combined with biochemical analysis allows an assessment of the liver condition in chronic exposure to mercury compounds in the place of settlement.
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PMID:The assessment of the condition of the liver in patients chronically exposed to mercury compounds in the place of settlement. 764 91

This study was aimed at clarifying the usefulness of the arterial ketone body ratio (AKBR), which reflects hepatic mitochondrial redox state and closely correlates with hepatic energy production, for understanding the degree of hepatic mitochondrial damage and the extent of the deterioration in hepatic energy metabolism during or shortly after hemorrhagic shock. Changes in the AKBR of 33 trauma victims who were admitted to our institute in hemorrhagic shock with a systolic pressure lower than 70 mmHg were measured until the patient recovered with the restoration of AKBR to the normal range (> or = 1.0) or until the patient died. During hemorrhagic shock the AKBRs were highly decreased, indicating deteriorated hepatic function. With successive fluid resuscitation the AKBR quickly recovered in 15 surviving patients from an initial value of 0.26 +/- 0.03 toward normal within hours, indicating that hepatic mitochondria are functioning normally. The AKBR recovered to a normal value of 1.10 +/- 0.06 on day 2 (p < 0.001). In 18 expired patients, AKBR did not recover to normal range, even though some of the patients recovered from the shock state. On the other hand, AST, ALT, LDH, and prothrombin time on day 2 were not significantly different from the values on admission, and the changes during the interval were not unidirectional even in the surviving patients, providing no information on the current functional state of the liver. Measurement of AKBR during and shortly after hemorrhagic shock provides timely and accurate information about liver function.
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PMID:Arterial ketone body ratio as a parameter of hepatic mitochondrial redox state during and after hemorrhagic shock. 767 5

To evaluate its clinical value, the half-life of caffeine (1,3,7-trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in 53 children with chronic liver disease (mean age, 4.41 years) and 48 control children (mean age, 6.26 years) in five samples over 24 h and compared with parameters of liver function and outcome. Sensitivity was 60.3% and specificity 97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p < 0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a clinical score of liver dysfunction calculated from the presence of features of hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were performed on 53 patients on 127 occasions during a mean follow-up of 361 days (range, 4-709). Of this group, 18 were listed for liver transplantation. Predictive values of outcome by analysis of variance expressed as ratio of mean squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p < 0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of severity of liver disease, but SBR was a better predictor of listing for liver transplantation in this group of paediatric patients.
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PMID:The prognostic significance of caffeine half-life in saliva in children with chronic liver disease. 771 86

The records of 47 patients with no cirrhosis who underwent 56 liver resections under total vascular exclusion (TVE) for malignant tumours, both primary and secondary, were reviewed to study the effects of TVE. The mean (s.e.m.) blood loss was 1651(233) (median 1200 (range 200-8500)) ml and the mean(s.e.m.) intraoperative blood transfusion 930(100) (median 700 (range 0-2800)) ml. In 18 liver resections (32 per cent) no blood transfusion was administered. The mean(s.e.m.) postoperative hospital stay was 19.7(14.2) days. The 30-day operative mortality rate was nil but the hospital mortality rate was 4 per cent. Postoperative prothrombin time was influenced by the amount of liver resected and the duration of TVE but not by the amount of blood transfused. Postoperative serum levels of aspartate aminotransferase and bilirubin were not influenced by either the amount of liver resected or the duration of TVE.
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PMID:Liver resection with total vascular exclusion for malignant tumours. 788 42

Infection of naive North American horses with 10(4) cell culture infectious doses (CCID50) of virulence variants of African horsesickness virus (AHSV), designated AHSV/4SP, AHSV/9PI, and AHSV/4PI, reproduced three classical forms of African horsesickness: acute (pulmonary), subacute (cardiac), and febrile, respectively. Distinct clinicopathologic and hemostatic abnormalities were associated with each form of disease. Hemostatic abnormalities included increased concentration of fibrin degradation products and prolongation of prothrombin, activated partial thromboplastin, and thrombin clotting times. Hemostatic findings indicated activation of the coagulation and fibrinolytic systems with clotting factor consumption in acute and subacute cases of African horsesickness. Hematologic abnormalities in acute and subacute cases of African horsesickness included leukopenia, decreased platelet counts, elevated hematocrit, and increased erythrocyte counts and hemoglobin concentration. Leukopenia was characterized by lymphopenia, neutropenia, and a left shift. Increased levels of serum creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase, hypocalcemia, hypoalbuminemia, hypoproteinemia, and elevated creatinine, phosphorus, and total bilirubin levels were present in some but not all horses. Metabolic acidosis, indicated by decreased total bicarbonate and increased lactate and anion gap, was present in horses with the acute form of disease. Mild thrombocytopenia and leukopenia were occasionally associated with the febrile form of disease. These results suggest a role for intravascular coagulation in the pathogenesis of African horsesickness.
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PMID:Clinical pathology and hemostatic abnormalities in experimental African horsesickness. 777 Oct 50

The distribution of the severity of preservation injury (PI), its association with acute early rejection, and its effect on graft and patient survival were examined in 151 patients transplanted between 9/88 and 12/91. PI was graded into mild, moderate and severe using prothrombin time (PT) on the 2nd POD and peak AST and ALT levels of the first 3 days after transplant. Of the 151 patients, 104 (68.8%) had minimal, 24 (15.9%) had moderate, and 23 (15.3%) had severe PI. The rate of early rejection, within 21 days after transplant, (54.8% vs 54.2% vs 52.2%) and its timing (10.0 +/- 0.5 vs 8.8 +/- 0.8 vs 8.9 +/- 1.4 days) as well as the incidence of steroid-resistant rejection (21.4% vs 33% vs 30%) did not differ significantly among groups. Graft survival was significantly lower in the severe PI group than among patients with minimal PI at 3 months and 24 months (65.2% vs 86.2%; p < 0.05 and 58.3% vs 82.7%; p < 0.05, respectively). Patient survival at 3 and 24 months was similar among the groups (91.1% vs. 95.8% vs 86.9% and 81.9% vs 91.1% vs. 74.3%). We conclude that the cellular damage associated with preservation injury does not predispose to development of acute rejection.
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PMID:Preservation injury in clinical liver transplantation: incidence and effect on rejection and survival. 781 18


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