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)

A total of 365 donor hepatectomies performed between May 1985 and March 1990 were reviewed and analyzed retrospectively to identify risk factors associated with poor graft function and to study the outcome of grafts retrieved from "marginal" donors. The donor mean age was 27.1 years (8-69 years). Mean ICU donor stay was 2.7 days (range 0 to 18 days), and the mean ischemic time was 8.6 hr (range 3 to 22 hr). The pancreas was retrieved in 39 donors. Donor's weight above 100 kg was the only variable found to be associated with both significantly increased 3-month graft loss (P less than 0.01) and early hepatocellular damage--AST or ALT greater than 2000 U/ml, 1st day posttransplant (P less than 0.02). Prolonged stay in the ICU (greater than 3 days), although associated with a significantly increased rate of hepatocellular damage (P less than 0.05), did not affect early graft survival. A systolic blood pressure less than 90 mmHg despite the use of high-dose dopamine (greater than 15 micrograms/mg/min), but not each of these variables itself, was also associated with a significantly increase rate of hepatocellular damage (P less than 0.001). All other variables, including age greater than 50, ischemic time greater than 12 hr, combined liver-pancreas procurement, and liver function test abnormalities, did not affect the outcome. We conclude that extending our limits to accept donors of the higher age group and those who have moderately abnormal liver function tests or a prolonged ischemic time will not jeopardize our results. It is suggested to perform liver biopsy in overweight donors during the retrieval to prevent using grafts with severe fatty infiltration. It is hypothesized that hormonal changes, starvation, and increased risk to develop infection might jeopardize the outcome of grafts from donors with a prolonged ICU stay. Although 70% of the early hepatocellular injuries are reversible, the remaining 30% result in graft failure.
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PMID:The use of marginal donors for liver transplantation. A retrospective study of 365 liver donors. 173 33

In a cross-sectional study of 181 male workers of a rotogravure printing plant, most of whom were exposed to toluene levels well above the GDR threshold limit values, 55 subjects revealed pathological liver screening values (activities of serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase; liver size). The differential diagnostic examination showed in 51 out of these 55 subjects an association with competing factors such as alcohol abuse (78%) and overweight (40%), to a slight extent disorders of fat and carbohydrate metabolism and of the gallbladder. Drug intake did not play any role. The variance and regression analyses of the biochemical data have shown that alcohol significantly and considerably increases the activities of all three enzymes tested. Bodyweight had a similar, but less pronounced, significant effect. On the other hand, in subjects with a higher alcohol intake the activities of liver enzymes in highly toluene exposed subgroups were significantly and clearly lower than among slightly toluene exposed workers.
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PMID:Epidemiological study on the hepatotoxicity of occupational toluene exposure. 289 31

The level of alanine aminotransferase (ALT) in blood donors has been related to the frequency of posttransfusion hepatitis in recipients. Sixty-seven donors with elevated ALT levels were evaluated to define the duration and significance of the elevation. The ALT level remained elevated in 41 donors (61%) for a mean interval of 9 months. The ALT level was greater than the aspartate aminotransferase in all of the donors. Alcohol intake did not correlate with ALT level. Donors with persistently elevated ALT levels had a significantly higher mean percent ideal body weight (128 +/- 3.9) than donors whose ALT level became normal (116 +/- 3.1). Nine donors with elevated ALT levels for at least 6 months had needle biopsies of the liver. Seven had prominent fatty vacuolization of hepatocytes without evidence of alcoholic hepatitis. One biopsy demonstrated chronic persistent hepatitis. No other cause for the elevated ALT levels could be identified. An overweight male donor with an isolated ALT elevation may need no further investigation unless clinical evaluation suggests a source of liver injury.
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PMID:The persistence and significance of elevated alanine aminotransferase levels in blood donors. 398 3

Liver morphology and biochemistry were investigated in 61 morbidly obese subjects selected by defined criteria. Median overweight was 82 per cent (range 61 to 170 per cent), and median duration of overweight was 20 years (range two to 45 years). No patient had more than a moderate alcohol consumption and only one was diabetic. Four biopsies (7 per cent) showed normal liver tissue, while fatty change was the main diagnosis in most cases (85 per cent). Increasing degrees of fatty change was significantly (P less than 0.02) associated with presence of lipogranulomas (found in 54 per cent of the biopsies), focal necroses (found in 28 per cent), slight parenchymal inflammation (found in 33 per cent), and Kupffer cell proliferation (found in 49 per cent). Slight portal inflammation was seen in 23 per cent but portal fibrosis in only 2 per cent of the biopsies. No case of cirrhosis was registered. Patients with moderate or severe fatty change, lipogranulomas , focal necroses or with parenchymal inflammation were significantly more obese than patients without these changes (P less than 0.05). Even in absence of fatty change, obese subjects showed a markedly decreased serum albumin concentration and an elevated serum alkaline phosphatase activity (P less than 0.0001) compared with non-obese controls. Serum lactate dehydrogenase and aspartate aminotransferase were significantly raised only in patients with fatty change. With respect to serum bilirubin and plasma cholesterol concentrations no significant differences were detected between patient subgroups and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The liver in consecutive patients with morbid obesity: a clinical, morphological, and biochemical study. 672 92

We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m2. Eighty-seven percent (290 of 333) of subjects were overweight (BMI > or = 25) and 34% (113 of 333) were obese (BMI > or = 30). Two percent (7 of 333) were morbidly obese (BMI > or = 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI > or = 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters.
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PMID:Correlates of body mass index in hazardous materials firefighters. 1041

Few mutations have been found in the human leptin gene and the relationship between leptin gene sequence variation and human overweight is uncertain. To determine whether sequence variation within the leptin gene and its regulatory elements contribute to extreme obesity, we screened approximately 3 kb of the 5' flanking region and the three exons in 125 unrelated extremely obese (BMI > or = 40 kg/m2) and 86 average weight women (BMI < 27 kg/m2). Within the protein coding regions only one heterozygous silent mutation was found (codon 102; AAC/AAT). Within the 5' flanking region, six frequent sequence variants were detected (q > 0.10), and the allele frequencies of three of these variants differed between obese and average weight Caucasian women (+19, chi 2 = 4.46, p = 0.035; -1823, chi 2 = 4.36, p = 0.037; -2548, chi 2 = 5.73, p = 0.017). Nine infrequent sequence variants were detected (q < 0.05) but they did not occur more often among obese women compared with those of average-weight. For extremely obese women, three polymorphisms (+19, -188, and -633) predicted the degree of obesity. Allelic variants may influence the regulation of the leptin gene and thereby influence body weight, particularly among extremely obese women. However, given the low variability in coding regions and the high variability in the 5' flanking region, discerning the functional significance of each variant is likely to be difficult.
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PMID:Sequence variants in the 5' flanking region of the leptin gene are associated with obesity in women. 1073 35

To investigate the associations between obesity and serum hepatic enzyme activities, we measured total body fat (TBF), body mass index (BMI), and hepatic biochemical parameters in 732 apparently healthy adults. TBF was assessed using a body fat analyzer. Serum activities of alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LD) were determined by standard spectrophotometric methods. Mean activities (+/- SD) of serum ALT and AST in men with high fatness were 51.2 +/- 12.6 U/L and 32.9 +/- 9.2 U/L, which were significantly higher than those in men with low fatness (23.5 +/- 7.4 U/L and 22.5 +/- 7.8 U/L, p < 0.01). Of 147 men with high fatness, 56 (38.1%) had serum ALT levels above the upper limit of normal, whereas only 9.5% (31/328) of men with low or desirable fatness showed elevated serum ALT activities (p < 0.01). Serum ALT, AST, and GGT activities correlated significantly with TBF in both overweight men and women. Among subjects having high TBF, those with fatty liver showed significantly higher incidence of elevated hepatic enzymes, compared to those without fatty liver. In short, elevated serum hepatic enzyme activities are associated with TBF and a high prevalence of fatty liver is observed in subjects with elevated TBF.
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PMID:Association between elevated serum hepatic enzyme activity and total body fat in obese humans. 1295 39

Thirty overweight patients with clinically characterized and biopsy proven nonalcoholic steatohepatitis (NASH) were enrolled in a 48-week treatment trial with rosiglitazone, a peroxisome proliferator-activator receptor (PPAR)-gamma agonist that enhances insulin sensitivity. Improvement in laboratory liver tests, insulin resistance and liver fat content were documented; blinded biopsy review demonstrated decreases in necroinflammatory activity or grade and in individual components of grade, and changes in the relationship of lobular and portal inflammation as well as in the nature of perisinusoidal fibrosis. The current study identified correlations of histological features of the protocol entry biopsy specimens with contemporaneous laboratory and imaging tests. Significant correlations with histologically assessed steatosis were liver fat, evaluated by computed tomography (P = 0.001); mean HbA1C, a measure of glycemic control (P = 0.004); and QUICKI, a measure of insulin sensitivity (P = 0.05). Histologically determined grades of steatohepatitis (SH) correlated with HbA1C (P = 0.01), and a trend toward elevated fasting glucose levels was seen. No subject in the study was cirrhotic at entry; fibrosis scores of the 30 subjects did not significantly correlate with age, gender, body mass index, or clinical tests. All subjects underwent 3 biopsies (prior, entry, and posttreatment), and all had undergone a prior biopsy with diagnostic SH. By blinded analysis, 7 study entry biopsy specimens did not fulfill published strict criteria for SH. Laboratory results from these subjects included normal fasting glucose level and, compared with the 23 subjects with criteria for SH, lower mean alanine aminotransferase and aspartate aminotransferase levels (P = 0.02 for both), less insulin resistance (P = 0.03), and lower mean HbA1C (P = 0.001). We conclude that biopsy findings determined by blinded analysis correlated with image-detected steatosis, laboratory markers of hepatic inflammation, insulin resistance, and long-term glycemia; the findings confirm the usefulness of strict histological criteria in the evaluation of NASH.
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PMID:Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. 1534 8

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.
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PMID:Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease. 1591 56

Childhood NAFLD has become an important childhood liver disease, and it is probably highly prevalent. The full of spectrum of NAFLD has been identified in children. It is not currently known whether or not simple hepatic steatosis in children is benign or whether it evolves to NASH over time. In contrast, childhood NASH certainly can have serious consequences. Cirrhosis is apparently rare in children with NAFLD, but it definitely occurs. Childhood NAFLD may occur in very young children, and there is no female predominance in the pediatric age bracket. Children present with vague abdominal pain, if they have any symptoms at all, but frequently hepatic steatosis is found incidentally on abdominal imaging. Laboratory studies show that serum aminotransferase abnormalities are rather moderate, with serum alanine aminotransferase (ALT) more elevated than serum aspartate aminotransferase (AST). Hypertriglyceridemia is the typical blood lipid abnormality, although hypercholesterolemia may occur. NASH may be more severe in children from certain ethnic groups, including Hispanics and Asians, or in association with certain metabolic disorders characterized by abnormalities in insulin receptor structure or signaling, such as lipodystrophy syndromes. Weight loss through dietary redesign and a regimen of regular exercise remains the mainstay for treatment for childhood NAFLD. A dietary strategy to minimize postprandial hyperinsulinemia and overall fat intake, such as a low glycemic index diet, may be the best dietary strategy. The real efficacy of drug treatments in children requires further investigation. The overriding message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.
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PMID:Non-alcoholic fatty liver disease (NAFLD) in children. 1597 Apr 96


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