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)

The effect of alcoholic patient sera on in vitro lymphocyte transformation was studied using mitogen-induced uptake of (3)H-thymidine to measure blastogenesis. With pokeweed mitogen as the stimulus, transformation of normal lymphocytes in sera of alcoholics with either normal or fatty livers was not significantly different from that obtained in pooled human serum (PHS). However, in sera of patients with either alcoholic hepatitis or inactive cirrhosis mean transformation was significantly reduced (P <0.001, <0.02 respectively). With phytohaemagglutinin-P or concanavalin A as mitogens, suppression of transformation was not as marked but followed the same pattern. A significant negative correlation was observed between the magnitude of transformation and serum bilirubin and aspartate aminotransferase levels. An intra-patient comparison of the effects on transformation of normal lymphocytes by simultaneously collected peripheral and portal venous sera, and of peripheral sera obtained before and after portasystemic shunt surgery, indicated that the factor(s) responsible did not originate in the splanchnic circulation nor did it accumulate in the serum because of failed hepatic clearance. By performing transformation experiments in the presence of inhibitory patient sera diluted with PHS it was possible to show that these sera caused true inhibition of transformation rather than suppression due to failure to sustain cell culture because of nutritional deficiencies. Inhibitory sera did not contain high levels of the enzyme thymidine phosphorylase and did not significantly inhibit binding of (125)I-labelled mitogens to the lymphocyte surface. These findings indicate that the inhibitory effect of sera from alcoholics is of potential in vivo importance, that the effect increases with the degree of heptocyte damage, and that it is unrelated to the nonhepatic metabolic affects of chronic alcoholism.
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PMID:Suppressive effect of alcoholic liver disease sera on lymphocyte transformation. 53 94

The extracellular matrix (ECM) is a complex of macromolecules that includes collagens, proteoglycans, and complex glycoproteins. In fibrotic liver tissue there is an increase in all of these matrix components, and they increase in serum in the patients with alcoholic hepatitis or liver cirrhosis. These ECM components have been used as a serum marker of hepatic fibrosis. Prolonged obstruction of bile flow results in morphologic and biochemical changes and the development of secondary biliary cirrhosis. In congenital biliary atresia (CBA) there is a close correlation between the degree of the hepatic fibrosis and bile flow after the operation. We estimated that, in CBA, ECM increased in serum, and it would reflect the degree of the hepatic fibrosis. To clarify this we examined the serum procollagen-III-peptide (P-III-P) and laminin in CBA patients. P-III-P was elevated in all preoperative patients but in two of the three postoperative patients whose jaundice disappeared P-III-P was in the normal range. In the all 3 patients whose jaundice continued, P-III-P was in normal range. Serum laminin was elevated in 12 preoperative patients with CBA, but there is no correlation between day of diagnosis and level of laminin. Mean concentration in CBA without jaundice after operation was 3.18 U/mL, 3.226 U/mL in CBA with jaundice and 3.3 U/mL in infantile hepatitis. There were no significant differences among three groups. With the elevation of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin, serum laminin level was also increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Laminin and procollagen-III-peptide as a serum marker for hepatic fibrosis in congenital biliary atresia. 150 Oct 26

Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.
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PMID:Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis. 219 90

We studied the relationship between the ratio of serum aspartate aminotransferase (ASAT) to alanine aminotransferase (ALAT) and histologic changes in human and experimental alcoholic liver disease. The patient population included 52 hospitalized patients enrolled in a Veterans Administration Cooperative study. The experimental animal group consisted of male Wistar rats fed an ethanol-liquid diet. Of the 52 patients with alcoholic hepatitis, 33 had evidence of cirrhosis. The mean +/- SD for the ASAT/ALAT ratio in the group with alcoholic hepatitis and no cirrhosis was 1.47 +/- 0.84, the mean +/- SD in the group with hepatitis and cirrhosis was significantly higher (2.68 +/- 1.32, p less than 0.01). There was no difference in the ratio between the rats with and without liver fibrosis. The cause for the increased ASAT/ALAT ratio in serum in the presence of cirrhosis is unknown and may reflect more severe liver damage.
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PMID:Serum aspartate aminotransferase to alanine aminotransferase ratio in human and experimental alcoholic liver disease: relationship to histologic changes. 270 13

The term chronic active hepatitis covers aetiologically different conditions with similar histological features. Autoimmune chronic active hepatitis - the type that was described originally - is the only type which responds well to prednisolone therapy. Autoimmune chronic active hepatitis can be differentiated from other types by serological and other markers. Treatment with prednisolone should be given for at least two years, with adjustment of dosage according to the serum levels of aspartate transaminase; maintenance does should be 8-12 mg a day. Azathioprine (50-100 mg a day) may be given concurrently as a corticosteroid-sparing agent. Prednisolone therapy in patients with autoimmune chronic active hepatitis enhances the quality of life and survival is prolonged greatly; currently the survival rate after 10 years for prednisolone-treated cases is at least 70%. Prednisolone is not effective in hepatitis B-associated chronic active hepatitis and may be deleterious. In cryptogenic chronic active hepatitis, in which markers of autoimmunity or hepatitis B viral infection are lacking, a trial of prednisolone therapy may be given for three months, and continued only if the indices of disease activity indicate a response. Corticosteroid agents have not proved of benefit in other liver diseases, including alcoholic hepatitis and acute liver failure, and a beneficial effect in primary biliary cirrhosis is yet to be established.
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PMID:Treatment of chronic active hepatitis and other liver diseases with corticosteroid agents. 356 Dec 94

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

The relationship between pyridoxal phosphate deficiency and activities of serum and liver aminotransferases was studied in 12 patients with alcoholic hepatitis. Plasma pyridoxal phosphate and the activities of liver aminotransferases were initially decreased in the patients, as compared with mean values in controls with normal hepatic histology. Addition of pyridoxal phosphate to liver homogenates increased liver alanine aminotransferase, but not aspartate aminotransferase, in all patients with initially low plasma pyridoxal phosphate. After 1 mo of abstinence from alcohol, with intake of an adequate diet and pyridoxine supplementation, plasma pyridoxal phosphate increased in all patients with initially low values (p less than 0.02). Serum aspartate aminotransferase decreased, whereas serum alanine aminotransferase increased, resulting in a decrease in their ratio in serum (p less than 0.001). Liver alanine aminotransferase increased (p less than 0.005), whereas liver aspartate aminotransferase remained unchanged. These data suggest that pyridoxal 5'-phosphate depletion is partially responsible for the low serum alanine to aspartate aminotransferase ratio that is typical of patients with alcoholic hepatitis.
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PMID:Relationship between pyridoxal 5'-phosphate deficiency and aminotransferase levels in alcoholic hepatitis. 669 65

Serum aspartate aminotransferase isoenzymes were measured in 123 hospital patients with various liver diseases, using a new and simple immunochemical method. Our findings show the usefulness of this determination in estimating the severity of hepatic damage, especially if accompanied by the measurement of other mitochondrial enzymes. During hepatic damage, the cytoplasmic isoenzyme is found in greater quantities than the mitochondrial isoenzyme, but the level of the latter increases to a greater extent in acute liver diseases. Moreover, the values of mitochondrial aspartate aminotransferase activity and the ratio of mitochondrial to total aspartate aminotransferase in alcoholic hepatitis are higher than expected if so-called hepatic enzymes commonly measured in serum are considered. These results indicate that there is significant mitochondrial damage in alcoholic hepatitis.
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PMID:Clinical and diagnostic significance of aspartate aminotransferase isoenzymes in sera of patients with liver diseases. 671 55

It has been shown recently that inactivation of Kupffer cells prevents free radical formation and early alcohol-induced liver injury, and that hypoxia subsequent to a hypermetabolic state caused by activated Kupffer cells is likely involved in the mechanism. Calcium is essential for the activation of Kupffer cells, which contain L-type voltage-dependent Ca2+ channels. Therefore, the purpose of this study was to determine whether a Ca2+ channel blocker, nimodipine, prevents early alcohol-induced liver injury in vivo and to evaluate its effect on intracellular calcium ([Ca2+]i) in Kupffer cells in vitro. Male Wistar rats were exposed to ethanol (10-12 g/kg/d) continuously for up to 4 weeks via intragastric feeding using an enteral model developed by Tsukamoto and French. In this model, ethanol causes steatosis, necrosis, and inflammation in only a few weeks. In the experimental group, nimodipine (10 mg/kg/d) was added to the diet and was shielded from direct light. Nimodipine had no effect on body weight over a 4-week treatment period, nor were mean ethanol concentrations or their cyclic pattern in urine affected. The mean urine ethanol values were 154 +/- 11 mg/dL in ethanol-fed and 144 +/- 38 mg/dL in ethanol + nimodipine-fed rats. After 4 weeks, serum aspartate transaminase (AST) levels were elevated in ethanol-treated rats to 183 +/- 78 U/L. In contrast, values only reached 101 +/- 9 U/L in rats given nimodipine + ethanol-values which were significantly lower. Steatosis and necrosis assessed histologically were also reduced significantly by nimodipine. Nimodipine (10 micrograms/kg) also blocked the swift increase in alcohol metabolism and elevated oxygen consumption in perfused livers from rats treated with alcohol in vivo. Further, in cultured Kupffer cells, nimodipine (1 mumol/L) largely prevented the elevation in [Ca2+]i caused by lipopolysaccharide (LPS) (LPS, 200 +/- 11 nmol/L; LPS + nimodipine, 94 +/- 31 nmol/L; P < .05). These results indicate that nimodipine prevents alcoholic hepatitis, possibly by inhibition of endotoxin-mediated Kupffer cell activation.
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PMID:Nimodipine, a dihydropyridine-type calcium channel blocker, prevents alcoholic hepatitis caused by chronic intragastric ethanol exposure in the rat. 869 Apr 10

Glycine prevents hepatic damage caused by hypoxia-reoxygenation, diminishes mortality due to endotoxin and minimizes alcoholic liver injury by decreasing blood ethanol. Our purpose was to investigate the effect of dietary glycine during recovery from early alcohol-induced injury, using a model that mimics the clinical presentation and histopathology with alcoholics. Male Wistar rats were exposed to ethanol continuously for 6 wk via intragastric feeding that resulted in typical histology of alcoholic liver injury, including steatosis, inflammation, necrosis and increased serum levels of aspartate aminotransferase and alanine aminotransferase. After cessation of ethanol, one group of rats received a control diet, the other a glycine-containing diet for 2 wk. During this period, all parameters studied tended to return to baseline values. However, serum aspartate aminotransferase and alanine aminotransferase recovered about 30% more rapidly in rats fed glycine. Further, the hepatic pathology score was also significantly lower in the glycine group than in controls (0.5 vs. 2.6). After 1 wk, steatosis was reduced significantly more in the glycine group (5. 6%) than in controls (8.9%). Glycine also diminished numbers of infiltrating leukocytes and necrotic cells significantly more than in controls. This beneficial effect of glycine may be partly explained by the fact that glycine increased influx of chloride into Kupffer cells leading to diminished tumor necrosis factor-alpha production. These results indicate that a glycine containing diet expedites the process of recovery from ethanol-induced liver injury and may lead to its clinical application in alcoholic hepatitis.
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PMID:Glycine accelerates recovery from alcohol-induced liver injury. 969 63


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