Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genomic DNA size was measured in three strains of Pseudomonas aeruginosa, ATCC 29260 (exotoxin A), ATCC 33467 (type I smooth) and ATCC 33468 (type 2 mucoid) by transverse alternating field electrophoresis of restriction fragments. Because of the high (67%) G + C content of Pseudomonas aeruginosa, restriction enzymes that recognize sequences with at least 4 AT base pairs were expected to be rare cutters. Eight enzymes produced fragments greater than 200 kb in size: Dral (TTT/AAA), Asnl (ATT/AAT), Hpal (GTT/AAC), AfIII (C/TTAAG), Xbal (T/CTAGA), Spel (A/CTAGT), Sspl (AAT/ATT) and Ndel (CA/TATG). All eight enzymes recognized one of three rare tetranucleotide sequences, TTAA, CTAG or ATAT. Pseudomonas aeruginosa strain 29260 has a genomic DNA size of 5573 kb. Strains 33467 and 33468 have identical restriction patterns and a possible deletion with a genomic size of 5407 kb.
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PMID:Determination of genome size of Pseudomonas aeruginosa by PFGE: analysis of restriction fragments. 197 59

The hepatoma-specific band of serum gamma-glutamyl transferase II (GGT II) and other three markers were evaluated in 77 patients with primary hepatocellular carcinoma (PHC). The positive rate of GGT II (87%) was much higher than that of the increased alpha-fetoprotein (AFP greater than or equal to 400 ng/ml, 54.5%), the increased alpha-1-antitrypsin (AAT greater than or equal to 400 mg/dl, 64.9%) and alkaline phosphatase isoenzyme I (ALP I, 13.0%). In patients with AFP less than 400 ng/ml, the positive rate of GGT II was 95.2%, higher than that of ALP I (22.8%) and AAT (60.0%). The positive rate of GGT II was positively correlated to the volume of PHC (r = 0.324, P less than 0.05), but even in patients with small PHC (less than or equal to 65 cm3), the positive rate of GGT II (78.6%) was higher than that of AFP (50.0%) and AAT (28.6%). The ALP I positivity was only seen in patients with larger PHC. Follow-up study showed that GGT II, like AFP, might occur before liver tumor could be detected by B-mode ultrasonography and computerized tomography. Therefore, GGT II is a valuable marker of PHC, especially in patients whose AFP was negative or slightly increased; GGT II may be useful for relatively early diagnosis of PHC.
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PMID:Reappraisal of diagnostic significance of a hepatoma-specific band of serum gamma-glutamyl transferase. 197 81

The conformation of the EcoRI dodecamer d(CGCGAATTCGCG)2 has been examined in solution by 1H and 31P NMR. Spin-spin coupling constants and nuclear Overhauser (NOE) enhancement spectroscopy show that all deoxyriboses lie in the south domain, with a small admixture of the north conformation (0-20%). The time dependence of the nuclear Overhauser enhancements also reveals a relatively uniform conformation at the glycosidic bonds (average angle, chi = -114 degrees). The average helical twist is 36.5 degrees (9.8 base pairs per turn). Tilt angles are small (in the range 0 to -10 degrees), and roll angles are poorly determined. Unlike single-crystal X-ray studies of the same sequence, there is no evidence for asymmetry in the structure. Both the NOE intensities and 31P relaxation data imply conformational anomalies at the C3-G4/C9-G10 and the A5-A6/T7-T8 steps. Berenil binds in 1:1 stoichiometry to the dodecamer with high affinity (Kd = 1 microM at 298 K) and causes substantial changes in chemical shifts of the sugar protons of nucleotides Ado 5-Cyt 9 and of the H2 resonances of the two Ado residues. No significant asymmetry appears to be induced in the DNA conformation on binding, and there is no evidence for intercalation, although the binding site is not centrosymmetric. NOEs are observed between the aromatic protons of berenil and the H1' of both Thy 7 and Thy 8, as well as to Ado 5 and Ado 6 H2. These results firmly establish that berenil binds via the minor groove and closely approaches the nucleotides Ado 6, Thy 7, and Thy 8. On the basis of quantitative NOE spectroscopy and measurements of spin-spin coupling constants, changes in the conformations of the nucleotides are found to be small. Using the observed NOEs between the ligand and the DNA together with the derived glycosidic torsion angles, we have built models that satisfy all of the available solution data. The berenil molecule binds at the 5'-AAT (identical to 5'-ATT on the complementary strand) site such that (i) favorable hydrogen bonds are formed between the charged amidinium groups and the N3 atoms of Ado 6 and Ado 18 and (ii) the ligand is closely isohelical with the floor of the minor groove.
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PMID:Interaction of berenil with the EcoRI dodecamer d(CGCGAATTCGCG)2 in solution studied by NMR. 199 Nov 17

A 43-year-old black man had an 18-year history of apical lung cystic-bullous disease. Following two episodes of spontaneous pneumothorax and two instances of thoracotomy for bullectomy and pleural abrasion, he was found to have an intermediate AAT deficiency with an MZ phenotype. It is believed that this is the first case of localized bullous lung disease to be reported in association with any degree of AAT deficiency. There is evidence that the cystic lesions progressed to form upper lobe bullae. It is postulated that the AAT deficiency may have played a role in this progression, as did the patient's cigarette smoking. Following two instances of surgery, CT scans of the lungs, compliance studies and complete pulmonary function tests show no further evidence of lung bullae or emphysema. The rarity of the Z variant of AAT in blacks is discussed.
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PMID:Intermediate alpha 1-antitrypsin deficiency with apical lung bullae and spontaneous pneumothorax. Presence of a Z variant in an American black. 203 55

The mitochondrial (m-AAT) and the cytoplasmic (c-AAT) isoenzyme activities of the glutamate synthesizing enzyme aspartate aminotransferase have been localized in the rat retina on the ultrastructural level using enzyme histochemistry. Reaction product of c-AAT was found selectively in cone pedicles, in presynaptic terminals of a subpopulation of amacrine cells and of horizontal cell processes, which are connected to rods. Rod spherules, terminals of cone-related horizontal cells and of bipolar cells reacted negatively, as well as ganglion cells, nerve fibre layer and optic nerve, m-AAT reaction product was found in all neuronal structures, most densely in the photoreceptor inner segments. The localization of c-AAT activity is in accordance with its presumed meaning in the production of releasable glutamate.
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PMID:Cytochemical demonstration of aspartate aminotransferase activity in the rat retina. 205 2

Homozygous PiZZ individuals with a serum deficiency due to a defect in the secretion of the alpha 1-antitrypsin protein are at risk of developing severe panlobular emphysema. Tobacco smokers are particularly exposed to the disease which begins at an earlier age. Treatment by substitutive therapy with alpha 1-antitrypsin concentrates seems to be the only possibility. A two years' clinical trial was performed in 9 PiZZ patients, with more than 1,500 infusions being administered weekly. Serum AAT levels were used as guidelines to follow biochemical changes in the protease-antiprotease balance. From 0.16 g/l initially, the AAT level rose to 0.57 g/l after 7 months. No adverse reaction was observed during the trial; the concentrated protein was well accepted, ant the antielastase activity of the protein recovered after injection was equivalent to the activity injected. An attempt to administer the infusions monthly was stopped when we observed a dramatic decrease of the serum AAT level. Clinically, stabilization of the symptoms was noted. No degradation was observed in the patients who took part in the trial, even if no real improvement was detected.
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PMID:[Evaluation after 2 years of substitutive treatment of PiZZ emphysema with alpha-1 antitrypsin. 9 cases]. 213 50

Four fibrolamellar liver carcinomas were surgically removed and were postoperatively examined. Three patients are alive roughly three years from surgery, and there are no signs of imminent recurrence, while the fourth case was diagnosed only two months back. The carcinomas had developed in non-cirrhotic livers which also produced negative responses to serological tests for hepatitis B. In flow cytometry, DNA indices were indicative of diploidy in two cases and aneuploidy in the other two. The highest DNA index value was recorded from the smallest tumour which could be assigned to the category of "minute HCC". No correlation was found to exist either between age, sex, and DNA index. Positive CEA reaction was immunohistochemically recorded from few tumour cells, whereas negative AFP responses were exhibited by all four tumours. Appearance of AAT in tumour cells was detected in three cases. High degree of differentiation, similarity between tumour and liver cells, and oncocytoid nature of cells were revealed by optical light and electron microscopy. This high degree of differentiation was additionally confirmed by two factors: glucose-6-phosphatase activity was preserved in all four tumours, adenosinetriphosphatase activity was histochemically detectable from certain points of the tumour cell membrane. Gamma-glutamyl-transpeptidase activity, too, was very strongly pronounced in all tumour cells, which, however, cannot be interpreted as a sign of differentiation. Membrane-bordered "dense-core" granules were visible in few tumour cells in two cases. Intensive granular serotonin reactions were immunohistochemically recorded from the majority of tumour cells in the same cases. Our histochemical and ultrastructural parameters have produced clear-cut evidence to the hepatocyte nature of FLC cells. Yet, the presence of secretory granules and positive serotonin reaction might possibly support the assumption that the FLC originates from those pluripotent cells of the liver which may develop in two directions, depending on the individual case, to become either hepatocytes or neurosecretory cells.
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PMID:[Fibrolamellar liver carcinoma]. 215 93

Data on ten variables and 16 biomarkers were obtained on 119 patients with newly diagnosed pulmonary cancer. The prognostic value of 16 biomarkers (alpha-1-antitrypsin [AAT], adrenocorticotropic hormone [ACTH], alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], human chorionic gonadotropin [HCG], immune complexes, immunoglobulins, N-terminal peptide of proopiomelanocortin [NTERM], and tumor-associated antibody [TAA]) was tested by adding these to the model of age, gender, stage, morphology, Feinstein's classification of symptoms, Karnofsky scale, leukocyte count, recent weight loss, and liver enzymes. Using Cox's regression method and a forward stepwise procedure, seven biomarkers (ACTH, AAT, AFP, calcitonin, HCG, TAA, and prolactin) entered the model. Elevated levels of cortisol and TAA were associated with longer survival. The selection of biomarkers by stepwise regression needs to be interpreted with caution, especially since the Z scores were found to be dependent on the particular variables included in the model. Furthermore, when dichotomized on maximum of the normal laboratory values, HCG and AFP were infrequently (2%) elevated. The lack of correlation among the biomarkers supports the hypothesis of random derepression of the genome of cancer cells. Further studies in improved modeling and the formulation of a biomarker index could enhance our understanding of the biology of cancer.
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PMID:The use of biomarkers in the prediction of survival in patients with pulmonary carcinoma. 216 76

Ascitic fluid alpha 1-antitrypsin (AF-AAT) was compared with ascitic fluid total protein (AF-TP) and the serum-ascites albumin gradient (SAAG) in the differential diagnosis of ascites. The study included 82 consecutive patients of which 42 had cirrhosis, 8 hepatoma (with cirrhosis), and 27 malignant ascites (peritoneal 18, liver 9). The concentration of AF-AAT (milligrams per deciliter) was significantly elevated (P less than 0.001) in hepatoma (174 +/- 123), malignant liver disease (232 +/- 119) and peritoneal neoplasms (376 +/- 106) in comparison with cirrhotics (66 +/- 33). In separating ascites caused by cirrhosis or malignancy, AF-AAT (discriminating limit of 120 mg/dl) had a 96% sensitivity, 95% specificity, and 96% diagnostic efficacy, which was superior to the 87% observed for AF-TP and 86% for the SAAG. Similar results were obtained for the A/S AAT ratio but this test was not available in all patients. AF-AAT was particularly useful in patients with malignancy causing portal hypertension as assessed by SAAG (hepatoma, malignant liver disease). We conclude that AF-AAT may be a valuable parameter in the differential diagnosis of ascites.
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PMID:Ascitic fluid alpha 1-antitrypsin. 216 27

Monocytes potentially express two mRNA species by alternative splicing of exons at the 5' end of the gene. During inflammation the plasma concentration of AAT can increase about three-fold. In a myelomonocytic cell line (U937), under basal conditions, two AAT mRNA species are produced. After stimulation by interleukin-6 (IL-6) one mRNA species is produced resulting from the exclusion of the second monocyte exon. These findings demonstrate a novel way in which the expression of mRNA can be modified in a single cell type.
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PMID:Exclusion of an exon in monocyte alpha-1-antitrypsin mRNA after stimulation of U937 cells by interleukin-6. 224 95


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