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: UNIPROT:P17174 (aspartate aminotransferase)
14,872 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

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 effect of a regular oral diet supplying 167 kJ/kg per d (40 kcal/kg per d) on nutritional state, liver function and serum lipid profile was assessed in thirty severely malnourished alcoholic cirrhotic inpatients. Their diet was monitored by a trained dietitian and they were vigorously encouraged to eat all meals served. One month after their entry into the study, protein and energy intakes were significantly higher (P < 0.001) in keeping with an improvement of their nutritional status as evaluated by means of height-creatinine index, muscular mid-arm circumference, tricipital skinfold thickness (P < 0.01 for all) and fat mass (P < 0.001). Assessment of liver function tests showed that levels of aspartate aminotransferase (EC 2.6.1.1), gamma-glutamyl transferase (EC 2.3.2.2) and bilirubin decreased (P < 0.05, P < 0.02 and P < 0.05 respectively) while prothrombin time values increased (P < 0.05). Similarly, serum albumin increased modestly while transthyretin did not change. Orosomucoid and C-reactive protein decreased (P < 0.001 and P < 0.01 respectively), indicating an improvement of the inflammatory state. Apolipoprotein A1 and high-density-lipoprotein (HDL)-cholesterol correlated with several tests of liver function and improved significantly during the study period (P < 0.001 and P < 0.02 respectively). Moreover, changes in cholesterol and HDL-cholesterol correlated with those in transthyretin (P < 0.02 and P < 0.05 respectively). The changes in ApoA1 and HDL-cholesterol were greater in patients whose fat mass increased significantly. Our findings show that adequate oral nutrition resulted in a better nutritional status in cirrhotics after 1 month of hospitalization. The serum lipid variables appeared to be more useful indicators of functional liver improvement than the classic liver function tests which rather indicate liver damage.
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PMID:One-month regular oral nutrition in alcoholic cirrhotic patients. Changes of nutritional status, hepatic function and serum lipid pattern. 782 13

The major causes of liver graft failure are acute rejection, technical failure, and primary nonfunction (PNF). This study was undertaken to determine whether delayed return of neuromuscular function correlates with allograft primary dysfunction in humans given vecuronium. Twenty-two adult patients undergoing orthotopic liver transplantation were given an initial dose of vecuronium, 0.1 mg/kg intravenously (i.v.). All patients recovered from vecuronium-induced neuromuscular block prior to explantation. No additional neuromuscular blocker was given until the liver graft was implanted and reperfused. Fifteen minutes after reperfusion another 0.1 mg/kg vecuronium was given IV and recovery time from attaining complete neuromuscular block to return of the fourth twitch of a train-of-four was recorded. Patients were divided into three groups according to postoperative liver function. Group I consisted of 17 patients with immediate normal liver graft function. Group II consisted of four patients with primary dysfunction (PDF) [peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2000 U/L, prothrombin time > 16 s, and poor quality and quantity of bile within 3 days postoperatively] which eventually recovered normal function. Group III consisted of one patient with PNF (uncorrectable coagulopathy, severe metabolic acidosis, rising AST and ALT, and minimal or no bile output), whose graft never recovered. Recovery time in Groups II and III was prolonged compared to Group I (P < 0.05). Recovery time in Group III was prolonged compared to Group II (P < 0.05). A test based on these results using a recovery time of > 135 min as a predictor of PDF has a sensitivity and specificity of 80% and 76%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Duration of vecuronium-induced neuromuscular block as a predictor of liver allograft dysfunction. 786 19

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
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PMID:A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis. 789 Sep 5

The allowable imprecision for laboratory tests has been estimated from criteria based on clinical and analytical test outcome. The analytical outcome criteria studied are the Clinical Laboratory Improvement Amendments (CLIA) criteria for proficiency testing. The clinical outcome criteria are estimates of medically significant changes in test results taken from a study in the literature. The estimates of allowable imprecision were obtained from quality-planning models that relate test outcome criteria to the allowable amount of imprecision and inaccuracy and to the quality control that is necessary to assure achievement of the desired outcome criteria in routine operation. These operating specifications for imprecision are consistently more demanding (require lower CVs) than the medically useful CVs originally recommended in the literature because the latter do not properly consider within-subject biological variation. In comparing estimates of allowable imprecision, the CLIA outcome criteria are more demanding than the clinical outcome criteria for aspartate aminotransferase (asymptomatic patients), cholesterol, creatinine (asymptomatic patients), glucose, thyroxine, total protein, urea nitrogen, hematocrit, and prothrombin time. The clinical outcome criteria are more demanding for bilirubin (acute illness), iron, potassium, urea nitrogen (acute illness), and leukocyte count. The estimates of allowable imprecision from analytical and clinical outcome criteria overlap for aspartate aminotransferase (acute illness), bilirubin (asymptomatic patients), calcium, creatinine (acute illness), sodium, triglyceride, and hemoglobin.
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PMID:Allowable imprecision for laboratory tests based on clinical and analytical test outcome criteria. 792 63


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