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)

To study the potential of multivariate classification methods in order to obtain more insight into abnormal laboratory data from patients with sickle cell disease, we investigated standard haematological and clinical chemical variables of 18 controls and 37 apparently healthy persons with heterozygous sickle cell disease (Hb AS), all women, using both univariate and multivariate classification methods. In the univariate method, those with Hb AS showed decreased serum log aspartate aminotransferase (log AST) activity, mean corpuscular volume and mean corpuscular haemoglobin (MCH) and increased sodium concentration. The multivariate method identified sodium, potassium, urea, uric acid, log AST, alanine aminotransferase and MCH as the variables that produced maximal separation between persons with Hb As and controls. It increased the 'non-error rate' for classification of persons with Hb AS by 16.4% compared with classification based on the variable, MCH, that produced maximal separation by the univariate method. The frequency distribution of percentage Hb S in the Hb AS group proved bimodal with maximal separation at 37.0% Hb S. The subgroup with 37.0% or less (n = 16) was considered to have concomitant heterozygous alpha-thalassaemia-2. In the univariate method the subgroup characterized by greater than 37.0% Hb S (n = 21) had increased serum sodium and uric acid concentrations, perhaps related to sickle cell nephropathy, whereas the subgroup with less than or equal to 37% Hb S did not. The multivariate method added information to the univariate method by additionally identifying abnormalities in serum potassium and urea concentrations in the former subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potential of descriptive linear discriminant analysis for studying clinical chemical and haematological data from persons with heterozygous sickle cell disease. 189 49

The relationship between riboflavin and pyridoxine status was studied in 40 patients with sickle cell disease (SCD) and 12 normal children by measuring activation coefficients of erythrocyte glutathione reductase (EGRAC) and aspartate transaminase (ASTAC). Prevalence of riboflavin deficiency was significantly lower in SCD (42.5%) than in control subjects (83%) and there was less pyridoxine deficiency in SCD (10.3%) than control subjects (54.5%). Aspartate transaminase (AST) activities in SCD patients were double those in control subjects. Pyridoxine status of patients, but not of control subjects, was directly affected by riboflavin status as judged from significant correlations between EGRAC and both AST activity and ASTAC. Poor riboflavin status in patients may be restricting availability of pyridoxal phosphate (PLP) due to combined effects of enhanced PLP requirements and effects of poor riboflavin status on the synthesis of PLP by pyridoxine phosphate oxidase (PPO). PPO activity was no different in the two groups.
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PMID:Dependence of pyridoxine metabolism on riboflavin status in sickle cell patients. 360 73

Serum ferritin, aspartate aminotransferase (AST), alkaline phosphatase and hydroxybutyrate dehydrogenase (HBD) were studied during 21 vaso-occlusive crises in 12 adults with sickle cell disease (11 SS, 1 S beta degrees). The patients comprised three groups: those who had been untransfused (4), those who had received occasional exchange transfusion in crisis (3), and those who had been multiply transfused (5). Serum ferritin concentrations in crisis were compared with those of the steady state value. Rises in serum ferritin concentrations occurred in all crises in all groups. Although AST, alkaline phosphatase, and HBD rose, there was no correlation between these and log ferritin concentrations. The clinical impression was that the degree of rise in ferritin related to the severity of the particular crisis, and the above results showed that haemolysis and liver damage were not causally related to this rise. An estimate of serum ferritin cannot be used to assess the state of iron balance in sickle cell disease unless the patient is in the steady state. The considerable rise in serum ferritin concentration found in crisis, however, may be a useful marker of the extent of vaso-occlusion and tissue damage.
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PMID:Serum ferritin concentration in sickle cell crisis. 395 15

A total of 78 children with diagnosis of sickle cell disease (HbSS) aged 1-12 years were involved in this study; while 60 normal children (HbAA) of the same age range served as controls. Serum levels of alanine aminotransferase (EC 2.6.1.2), aspartate aminotransferase (EC 2.6.1.1), total protein and albumin were assayed in all the sickle cell children both in crises and steady state and in all the normal children. During crises, most of the sickle cell children had significantly raised levels of serum aminotransferases together with reduced levels of serum total protein and albumin. When these levels are compared with the ones observed during the steady state, the differences are highly significant. On the other hand, when the results obtained during the steady state are compared with those of the control group, the differences are not significant. These results are discussed in relation to the hepatic degenerative changes observed in sickle cell crises. It is clear from this study that the more clinical painful crises the children experience, the hepatic cells would be exposed to persistent injury which may eventually result in cell death.
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PMID:Serum aminotransferase activities in sickle cell children during crises. 614 89

Fifty-nine patients with homozygous sickle cell anaemia, 17 heterozygous individuals and 22 controls were investigated in respect to serum (S) 5'nucleotidase (5'NT, EC 3.1.3.5). The patients showed a significantly higher mean value of S-5'NT compared to the controls. However, this rise was heterogeneous as it occurred only among a subgroup of patients. The heterozygous individuals were not different from either the patients or the controls generating a situation which puts the heterozygous individuals in an intermediate position between the patients and the controls. S-5'NT showed significant correlation with S-bilirubin, S-aspartate aminotransferase, S-alanine aminotransferase and especially S-gammaglutamyl transferase. However, it was not correlated with S-alkaline phosphatase, which is another marker for hepatobiliary disease. These results suggest that the liver involvement in a subgroup of patients with sickle cell anaemia is a mixture of hepatocyte damage and the biliary tree involvement.
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PMID:Increased activity of 5' nucleotidase in serum of patients with sickle cell anaemia. 790 22

Abnormalities of nitric oxide metabolism have been implicated in the pathogenesis of acute chest syndrome in subjects with sickle cell anemia. It is not known whether exhaled nitric oxide levels (FE(NO)) are abnormal in children with a history of the acute chest syndrome (ACS). We compared FE(NO), plasma nitric oxide metabolites (NO(x)), serum arginine and citrulline levels, and the number of AAT repeats in intron 20 of NOS I in subjects with sickle cell disease (SCD) and a history of at least one episode of ACS (ACS(+), n = 13), subjects with SCD and no prior history of ACS (ACS(-), n = 7), and healthy children (HC, n = 6). Mean +/- SD FE(NO) (ppb) was lower in ACS(+) than in ACS(-) and HC: (10.4 +/- 4.3 versus 23.4 +/- 6.1 p = 0.002] and 30.4 +/- 15.8 [p = 0.0001], respectively). Plasma NO(x) (microM) were similar in all three groups (37.3 +/- 19.4, 33.0 +/- 13.2, 44.7 +/- 7.8, respectively). Arginine and citrulline levels (microM) did not differ between ACS(+) and ACS(-) groups. Spirometric data revealed a mildly diminished FEV(1) and FVC in ACS(+) that was statistically different from HC but not ACS(-): (FEV(1) as % of predicted for ACS(+), ACS(-), and HC; 83 +/- 17 versus 87 +/- 16 versus 102 +/- 16, respectively, p < 0.05 between ACS(+) and HC). The level of FE(NO) was significantly associated with the sum of AAT repeats in intron 20 of NOS I gene alleles. The correlation coefficient (r) was 0.62 (p < 0.005). We conclude that FE(NO) levels are significantly reduced in subjects who have a history of ACS and that the FE(NO) levels are significantly correlated with the number of NOS I AAT repeats. FE(NO) is a sensitive marker and may be a predictor of ACS prone children.
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PMID:Low exhaled nitric oxide and a polymorphism in the NOS I gene is associated with acute chest syndrome. 1175 Nov 85

Priapism, although uncommon in the general population, is one of the many serious complications associated with sickle cell disease (SCD). Few studies have described the clinical and hematologic characteristics of individuals with priapism and SCD. Using data from the Cooperative Study for Sickle Cell Disease, we assembled 273 case subjects with priapism and 979 control subjects. Case subjects, compared with control subjects, had significantly lower levels of hemoglobin; higher levels of lactate dehydrogenase, bilirubin, and aspartate aminotransferase; and higher reticulocyte, white blood cell, and platelet counts. These findings suggest an association of priapism with increased hemolysis. Hemolysis decreases the availability of circulating nitric oxide, which plays an important role in erectile function.
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PMID:Hemolysis-associated priapism in sickle cell disease. 1598 42

Pulmonary hypertension is prevalent in adult patients with sickle cell disease and is strongly associated with early mortality and markers of hemolysis, in particular, serum lactate dehydrogenase (LDH). Intravascular hemolysis leads to impaired bioavailability of nitric oxide (NO), mediated by NO scavenging by plasma oxyhemoglobin and by arginine degradation by plasma arginase. We hypothesized that serum LDH may represent a convenient biomarker of intravascular hemolysis and NO bioavailability, characterizing a clinical subphenotype of hemolysis-associated vasculopathy. In a cohort of 213 patients with sickle cell disease, we found statistically significant associations of steady-state LDH with low levels of hemoglobin and haptoglobin and high levels of reticulocytes, bilirubin, plasma hemoglobin, aspartate aminotransferase, arginase, and soluble adhesion molecules. LDH isoenzyme fractionation confirmed predominance of LD1 and LD2, the principal isoforms within erythrocytes. In a subgroup, LDH levels closely correlated with plasma cell-free hemoglobin, accelerated NO consumption by plasma, and impaired vasodilatory responses to an NO donor. Remarkably, this simple biomarker was associated with a clinical subphenotype of pulmonary hypertension, leg ulceration, priapism, and risk of death in patients with sickle cell disease. We propose that LDH elevation identifies patients with a syndrome of hemolysis-associated NO resistance, endothelial dysfunction, and end-organ vasculopathy.
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PMID:Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. 1629 95

Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age-adjusted comparisons showed that sickle cell anaemia-alpha thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF-beta/BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF-beta/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis-driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.
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PMID:Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. 1668 47

The main objectives of this paper were to test the hypothesis that polymorphisms in NOS1 and NOS3 genes associate with ACS in SCD patients and to characterize the association between physician-diagnosed asthma and acute chest syndrome (ACS). Case-control study of sickle cell disease patients >or=5 years old with ACS (cases; n=86) and those without ACS (controls; n=48) was carried out. Associations between ACS and the AAT repeat in intron 13 (formerly intron 20) of the NOS1, and with NOS3 T-786C polymorphism were explored. Physician-diagnosed asthma was determined by chart review, patient- or parent (guardian)-reported asthma, and drug use. Eighty five percent of participants with asthma had at least one episode of ACS compared to 14.6% of controls: adjusted odds ratio (OR) (95%CI) 5.46 (2.20,13.5), P= or<0.0001. Asthma correlated with the number of episodes of ACS (P<0.001). NOS1 AAT repeat polymorphism associated with the risk of ACS (P=0.001) in patients without physician-diagnosed asthma. No associations were found between the genotype of the NOS3 T-786C SNP and ACS. Physician-diagnosed asthma is a major risk factor for ACS. NOS1 AAT repeat polymorphism may contribute to physician-diagnosed asthma.
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PMID:Physician-diagnosed asthma and acute chest syndrome: associations with NOS polymorphisms. 1735 27


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