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)

In the end-stage renal disease patient, certain uremic compounds could influence the cellular accumulation of aluminum (Al). In this study, we examined the effect of 15 uremic ultrafiltrate fractions obtained by HPLC on the uptake and toxicity of Al in mouse hepatocytes (MH) in culture, a model system in which Al is taken up bound to transferrin (Tf). Uremic fractions 4 to 8, 12, 14, and 15 increased cellular Al uptake and aspartate aminotransferase release and decreased cell growth when Tf-Al, not Al citrate, was added to culture media. Compounds that have been extracted previously from these ultrafiltrate fractions (p-cresol, xanthine, tryptophan, hippuric acid, and o-hydroxyhippuric acid) were then tested for their effect on Al uptake and toxicity in MH at concentrations found in uremic serum. Significant Al uptake by MH was observed only when p-cresol was added together with Tf-Al. Time-response curves showed increased Al uptake and toxicity at p-cresol concentrations of 3 mg/dl in culture media. Dose-response curves confirmed that Al uptake and cell toxicity were proportional to p-cresol from 1.5 mg/dl to 3 mg/dl in culture media. p-Cresol was not toxic to MH in the absence of Tf-Al in media. p-Cresol increased Tf-associated Al uptake only because there was no effect on Al uptake when Al citrate was substituted, and studies with Tf-I125-Al in the presence of this compound showed increased Tf-I125 taken up by MH. p-Cresol did not increase Tf saturation with Al. p-Cresol also increased Tf-Al uptake in Friend erythroleukemia and neuroblastoma cells in culture. Our studies suggest that p-cresol and uremic fractions 4 to 8, 12, 14, and 15 increase the uptake and toxicity of Al in cultured MH. These compounds may play a role in the accumulation and toxicity of Al in the liver of end-stage renal disease patients and possibly in all cells that express Tf receptors.
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PMID:P-Cresol, a uremic compound, enhances the uptake of aluminum in hepatocytes. 918 61

Carbohydrate-deficient transferrin (CDT) has been proposed as a marker of alcohol abuse. However, its value in patients with associated liver disease is still controversial. The aim of the study was to investigate the usefulness of CDT as a marker of alcohol consumption in patients with liver disease. We measured serum levels of CDT and those of commonly used hematological and biochemical markers, mean corpuscular volume (MCV), transaminases (AST and ALT), and gamma-glutamyltransferase in 179 male subjects divided into four groups: 45 active drinkers (13 with normal liver, 21 with fibrosteatosis, and 11 with liver cirrhosis), 45 abstinent chronic alcoholics (18 with and 27 without liver disease), 58 patients with nonalcoholic liver disease, and 31 healthy controls. Serum CDT in active alcoholics was 37.5 +/- 3.6 units/liter, being significantly higher than that of abstinent alcoholics (20.3 +/- 1.5 units/liter), patients with nonalcoholic liver disease (18.1 +/- 1.1 units/liter), and controls (13.1 +/- 0.8 units/liter). Contrary to the other markers, no significant differences were observed in CDT values in relation with the presence and severity of liver disease in either the active drinkers or in the abstinent alcoholics. The sensitivity and specificity of CDT as a marker of alcoholism in the series as a whole was 64% and 82%, respectively, similar to the best conventional marker, MCV (64 and 82%). In patients with liver disease, CDT maintained good sensitivity (72%) and specificity (83%). Receiver operating characteristic analysis confirmed that CDT had a similar diagnostic value to that of MCV, but better than gamma-glutamyl-transferase and transaminases for the detection of alcohol abusers. The good diagnostic efficacy of CDT remained unchanged when analyzing only patients with liver disease. We conclude that serum CDT is a good marker of alcoholism and is less influenced than the currently used biochemical markers for associated liver disease. Thus, CDT is an effective laboratory test to detect alcohol abuse regardless of the presence of alcoholic liver disease.
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PMID:Carbohydrate-deficient transferrin as a marker of alcohol consumption in male patients with liver disease. 926 45

We have compared beta-hexosaminidase (beta-Hex) activity, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values in serum from male alcoholic patients with the corresponding values in moderate and non-drinking subjects. The total beta-Hex activity was 2.5 times higher in the alcoholics than in the moderate drinkers and this increase was mainly due to a 5-fold increase in the activity of the B-isoform of the enzyme. This was expressed as a percentage of the total beta-Hex activity and called 'beta-Hex B%'. Strong correlations were found between alcohol consumption (g/ day) and beta-Hex B% (r = 0.757, P < 0.001, n = 42), alcohol consumption and CDT (r = 0.671, P < 0.001, n = 42), and beta-Hex B% and CDT (r = 0.628, P < 0.001, n = 57). Serum beta-Hex B% had a sensitivity of 94% and a specificity of 91% in detecting alcoholic drinking of > 60 g/day. As a single marker of alcoholic drinking, it was markedly more sensitive than MCV and the liver enzymes GGT, AST and ALT, and slightly more sensitive than serum CDT (94 vs 83%). At the CDT cut-off level of 20 U/l, 17% of the moderate and non-drinkers would have been classified as alcoholic drinkers and 17% of the alcoholics would have been classified as moderate drinkers. Some of these misclassifications were eliminated if the beta-Hex B% results were taken into account. We suggest that serum beta-Hex B% can be a useful and inexpensive laboratory test for alcohol abuse.
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PMID:Comparison of serum beta-hexosaminidase isoenzyme B activity with serum carbohydrate-deficient transferrin and other markers of alcohol abuse. 946 24

The stage of human African trypanosomiasis (HAT) is important to define precisely as far as it is directly related to the type of treatment used. The beginning of the neurological involvement is difficult to find out because there is no known specific clinical or biological sign. This study is trying to look for a precise marker and has been realized in Congo. 70 subjects with parasitologically confirmed HAT and 70 controls are included. The stage of HAT is determined according to the classical definition on the field using the cerebrospinal fluid (CSF) cell count: less than 5 cells/microliters for the first stage (P1), more than 5 cells/microliters for the second stage (P2). The blood analysis has included: glucose, urea, creatinine, sodium, potassium, calcium, chloride, phosphorus, uric acid, total bilirubin, unconjugated bilirubin, total cholesterol, triglycerides, total proteins, aspartate aminotransferase, alanine aminotransferase, creatinine phosphokinase, alkaline phosphatase, gamma-glutamyltransferase, immunoglobulins M and G, C3c fraction of complement, transferrin, seromucoid alpha 1, haptoglobin and albumin. In CSF we have analyzed IgM, IgG, protein levels and the bloodbrain barrier (BBB) impairment. The comparison between the subjects and their controls, the subjects in P1 and in P2, the CSF cell count and the other CSF alterations show the interest of the IgM level in CSF and the BBB impairment to identify subjects in P2. However there is a low gradation in the biological disturbances and not a precise threshold point. Nevertheless it seems reasonable to raise the CSF cell count level to 20 cells/microliters to define the beginning of the nervous involvement.
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PMID:[Contribution of biochemical tests in the diagnosis of the nervous phase of human African trypanosomiasis]. 950 61

Carbohydrate-deficient transferrin (CDT) is known to be increased in alcohol abuse. Several methods were developed for its measurement (e.g. isoelectric focusing with Western blotting or immunofixation, anion-exchange chromatography followed by immunoassays). We describe a greatly simplified isoelectric focusing technique which does not require immunofixation. CDT results obtained with this method were compared to other biological markers of alcohol abuse, i.e. mean corpuscular volume (MCV), aspartate aminotransferase (ASAT) and gamma-glutamyl-transferase (GGT), in 55 patients distributed in three groups (i.e. healthy control subjects, control patients suffering from various hepato-gastrointestinal diseases and alcohol abusing patients). Sensitivity and specificity were 33-89%, 61-57%, 89-49% and 83-100% for MCV, ASAT, GGT and CDT, respectively. We conclude that our method is highly suitable for routine clinical use.
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PMID:A simple method for carbohydrate-deficient transferrin measurements in patients with alcohol abuse and hepato-gastrointestinal diseases. 954 99

To test the hypothesis that the quantities of circulating transferrin receptors are reduced in iron overload, we studied serum transferrin receptors and indirect measures of iron status in 150 subjects from rural Zimbabwe. We found significant inverse correlations between serum concentrations of transferrin receptors and ferritin, the ratio of ferritin to aspartate aminotransferase, and transferrin saturation (r > or = 0.44; P < 0.001). The mean +/- SD concentration of serum transferrin receptors in 23 subjects classified as having iron overload (ferritin > 300 microg/L and transferrin saturation > 60%) was 1.55 +/- 0.61 mg/L, significantly lower than the 2.50 +/- 0.62 mg/L in 75 subjects with normal iron stores (ferritin 20-300 microg/L and transferrin saturation 15-55%; P < 0.0005) and the 2.83 +/- 1.14 mg/L in 8 subjects with iron deficiency (ferritin < 20 microg/L; P = 0.001). In keeping with the regulation of transferrin receptor expression at the cellular level, our findings suggest that serum transferrin receptors are decreased in the presence of iron overload.
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PMID:Serum transferrin receptors are decreased in the presence of iron overload. 955 May 56

Brief intervention is a promising treatment for heavy drinking. The present study examined the diagnostic value of carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) in detecting early-phase heavy drinkers for brief intervention treatment in primary health care. Laboratory data were collected from consecutive 20- to 60-year-old, early-phase heavy drinkers (329 males and 136 females), who were willing to undergo brief intervention treatment in five primary health care outpatient clinics. An elevated value of at least 1 of the 5 markers studied was found in 75% of the male and in 76% of the female heavy drinkers. The sensitivities of CDT, MCV, AST, ALT and GGT values were low; in men, respectively, 39%, 28%, 12%, 28%, and 33%, and in women 29%, 40%, 20%, 29%, and 34%. However, marker combinations, including CDT, reached a good level of sensitivity; the best triple combination (CDT or MCV or GGT) was positive in 69% of the men and 70% of the women. According to logistic regression, the age of the patient had an increasing effect on MCV, ALT and GGT. High body mass index increased all transaminases and decreased CDT and MCV. Smoking increased MCV and decreased AST. Thus, primary health care marker combinations, especially those including CDT, should be considered for the detection of early-phase heavy drinkers for brief intervention treatment.
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PMID:Carbohydrate-deficient transferrin and conventional alcohol markers as indicators for brief intervention among heavy drinkers in primary health care. 966 Mar 18

Carbohydrate-deficient transferrin (CDT) has emerged as the best new marker for alcohol abuse. Recently plasma immunoglobulin A (IgA) reactivity with acetaldehyde (AcH)-modified proteins, or the modified proteins per se, have been proposed as a markers for high levels of alcohol consumption. In this study, we have compared CDT, IgA reactivity with AcH adducts (IgA ASR), and AcH-modified albumin with conventional markers of high alcohol intake in groups with well-defined drinking histories. The plasma activity of ALT, AST, and gamma-glutamyltransferase increased steadily with increasing alcohol consumption. CDT and AcH-modified albumin showed a similar pattern, whereas IgA ASR appeared only to be elevated after a threshold level of consumption had been reached. Neither CDT IgA ASR or AcH-modified albumin correlated strongly with any of the conventional markers or each other. This study shows that CDT, IgA ASR, AcH-modified albumin, and the conventional markers are not related, but suggests that the concurrent use of CDT and IgA ASR may lead to better identification of high alcohol intake.
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PMID:Comparison of carbohydrate-deficient transferrin, immunoglobulin A antibodies reactive with acetaldehyde-modified protein and acetaldehyde-modified albumin with conventional markers of alcohol consumption. 988 34

The results of the determination of 24 basic blood chemistry variables from 262 men and 239 women, half of each group 44.4 +/- 0.9 and 63.0 +/- 0.9 (men) and 44.4 +/- 0.9 and 62.8 +/- 0.8 years old (women), resp., are compared. In men, only 6 analytes show significant differences between the age groups: Alanine aminotransferase decreases, aspartate aminotransferase decreases, iron decreases with p < 0.05; sodium increases, calcium decreases, protein (serum) decreases with p < 0.001. In women, 16 analytes, compared between both groups, are significantly different: Urea, uric acid, creatinine, triglycerides, total cholesterol, LDL cholesterol, LDL-C/HDL-C ratio, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, sodium and ferritin are increased in the older group, whereas HDL cholesterol, iron, transferrin, and total protein are decreased. The sex differences are more distinct in the group of 44 years old persons than in the 63 years old one. These results will be completed by the comparison with the evaluation of the stored laboratory values of 9923 patients between 20 and 89 years old.
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PMID:[Clinical laboratory diagnosis and aging. 1: Results of data evaluation of clinico-chemical laboratory values in a study of aging]. 1040 12

We studied the associations of macrophage activity, T-helper cell types 1 and 2 (Th-1/Th-2) responses, and iron status in 55 patients with hepatitis C virus (HCV)-related liver disease and 28 control patients with noninfectious liver disease. Serum concentrations of soluble tumor necrosis factor receptor type II (sTNFrec 75), a macrophage activation marker, were higher in cirrhotic than in noncirrhotic patients (P<.001) regardless of their HCV status, whereas levels of neopterin, interleukin (IL)-4 and IL-10 did not differ significantly. In HCV-positive patients, sTNFrec 75 levels and transferrin saturation (TfS) correlated positively with levels of aspartate transaminase (P<.001 for sTNFrec 75 and P=.028 for TfS) and alanine transaminase (P=.003 for sTNFrec 75 and P=.039 for TfS). Increased TfS correlated significantly with both advanced liver disease and a predominant Th-2 pattern in HCV patients. Our data suggest that an association exists between macrophage activation and hepatic dysfunction, and that iron status may affect the clinical course of HCV infection by modulating Th-1/Th-2 responses in vivo.
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PMID:Associations between cellular immune effector function, iron metabolism, and disease activity in patients with chronic hepatitis C virus infection. 1051 3


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