Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.107 (DAT)
 1,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2,4-Diaminotoluene (2,4-DAT) is a mutagenic and hepatocarcinogenic aromatic amine, requiring metabolic activation. We have found that the mutagenic potency of 2,4-DAT in Salmonella TA98 is similar when activated by either Aroclor-1254-induced rat primary hepatocytes or 9000 x g supernatant. Previous work has demonstrated that 2,4-DAT is activated by cytochrome P450. The present report describes an investigation of the role of acetyltransferase in 2,4-DAT activation. Substitution of TA98 with the acetyltransferase-deficient strain TA98/1,8-DNP6 resulted in an approximately 90% decrease in the mutagenic potency for 2,4-DAT using S9 activation. The newly engineered acetyltransferase-enhanced Salmonella tester strain YG1024 (TA98(pYG219] demonstrated greatly enhanced sensitivity to the mutagenicity of 2,4-DAT. Inhibition of O-acetyltransferase activity, either with the selective acetyltransferase inhibitor thiolactomycin, or by competitive inhibition with an alternative substrate for the enzyme, reduced the mutagenicity of 2,4-DAT in this acetyltransferase-enhanced bacterial strain. From these data we conclude that following 2,4-DAT activation by N-hydroxylation by cytochrome P450, the resulting hydroxylamino intermediate is further activated in the bacteria via O-acetylation to form the ultimate reactive intermediate, which is postulated to be 4-acetoxyamino-2-aminotoluene.
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PMID:Evidence for an acetoxyarylamine as the ultimate mutagenic reactive intermediate of the carcinogenic aromatic amine 2,4-diaminotoluene. 223 26

We tested a revised version of the Hierarchic Dementia Scale (HDS), proposed by Cole and Dastoor (1980), in order to improve its clinical usefulness and to enrich our knowledge about ageing. The scale was built with 20 subtests which covered the entire range of cognitive and motor functions. Each subtest was hierarchically organized so that success in a item implied success in inferior items. This hierarchical principle was time-saving and was validated by Cole and Dastoor. 149 control subjects performed this test. They were equally divided in 4 age-groups (55-64, 65-74, 75-84, 85-97) and 2 educational levels. None of these subjects had previous history of somatic or neuropsychiatric disease. They were completely self-sufficient in daily life. A large part of the controls failed in the most difficult items of some subtests: Learning, Calculation, Mental Control, Drawing, Recall, Similarities, Constructional Praxis. For these subtests, significantly different mean-scores were observed between age-groups and educational levels. However, the influence of each factor was variable from one subtest to another. Moreover, subgroups seem to exist in our population according to specific difficulties in some of these subtests. This study calls for caution in the interpretation of results in demented patients. Comparisons with other psychometric tools remain to be performed. This scale seems to be more useful for the quantification and follow-up of cognitive deficits than for the early diagnosis of dementia. In addition, this scale, which briefly explores many aspects of cognitive functions, seems especially useful to approach the heterogeneity of DAT.
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PMID:[Standardization of a modular and hierarchic cognitive evaluation scale applicable to dementia. A French version of the Hierarchic Dementia Scale]. 223 94

IgG subclasses (G-sub) of warm red cell autoantibodies (anti-Rs) were examined by means of antiglobulin test (DAT) using anti-IgG1, 2, 3, and IgG4 sera (Holland Red Cross) on 12 AIHA, and on 5 cases being DAT positive caused by alpha-methyldopa (alpha MD). In 4 of 5 AIHA cases complicating SLE, the anti-Rs comprised not only IgG, but also IgA, IgM and C3; their G-sub were IgG1 + 2 in 2 and IgG1 + 2 + 3 + 4 in the other 2. In all of the 3 cases with idiopathic AIHA, anti-Rs comprised IgG alone (IgG1 alone, IgG1 + 3 or IgG1 + 2 + 3 in each one). All of the 5 alpha MD induced anti-Rs comprised IgG1 alone. Observation of the course of AIHA revealed that, although IgG3 tended to correlate with their anemia, this trend was not universal. Besides, the G-sub were not related to the anti-Rs titers. Furthermore, the immunological aberrations in patients with AIHA + SLE were found to be more complicated.
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PMID:[IgG subclasses of warm red cell autoantibodies in autoimmune hemolytic anemia]. 224 36

We examined patients with Dementia-Alzheimer's Type, depression, and matched controls on tasks designed to compare automatic (monitoring frequency and modality) and effortful (free recall) processing of words and pictures. The results demonstrated that depressed patients performed poorly only when conditions required effortful processing, but DAT patients performed poorly under all conditions. There was almost no overlap in scores between DAT and elderly depressed patients on one of the measures of automatic processing suggesting that this measure may be clinically useful. The results suggest that automatic memory processes can be partially dissociated from effortful memory processes, but that both types of operations are impaired in DAT patients.
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PMID:Automatic memory processes in patients with dementia-Alzheimer's type (DAT). 224 37

A multiply transfused patient was referred for evaluation of a transfusion reaction. The direct and indirect antiglobulin tests (DAT, IAT) for alloantibody were negative. However, IgG-coated control cells failed to agglutinate in the negative reactions, casting doubt on their validity. At 4 degrees C, the patient's serum exhibited a large cryoprecipitate (2.9 mg/mL), made up predominantly of an IgG kappa paraprotein and having trace amounts of IgM and C3. Clear serum separated at 37 degrees C became cloudy within 10 minutes at room temperature (RT); within 4 hours, approximately 60 percent of the total precipitable cryoprotein had precipitated. Red cells (RBCs) incubated in fresh serum that had cooled to RT or RBCs obtained from RT or refrigerated samples contained cryoprecipitate that sedimented with the RBCs during washing with RT saline. On resuspension, enough IgG cryoglobulin redissolved to neutralize completely the commercial anti-IgG reagents. If the patient's samples were maintained at 37 degrees C, cryoprecipitate did not form, and RBCs washed four times at 37 degrees C gave valid DAT and IAT reactions. The removal of all cryoprecipitate from the patient's serum by centrifugation after overnight incubation at 4 degrees C also made possible valid antibody screening and compatibility tests.
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PMID:Invalidation of antiglobulin tests by a high thermal amplitude cryoglobulin. 230 43

The enzyme acetylcoenzyme A:deacetylvindoline 4-O-acetyltransferase (EC 2.3.1.-) (DAT), which catalyzes the final step in vindoline biosynthesis in Catharanthus roseus, was purified 3300-fold using ammonium sulfate precipitation followed by gel filtration, anion exchange, hydroxyapatite, and affinity chromatographies. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the purified DAT showed the presence of two major proteins having Mr values of 33,000 and 21,000, whereas native PAGE showed three protein bands, and isoelectric focusing-PAGE one diffuse protein band (pI = 4.7-5.3) plus two minor protein bands (pI = 5.7 and 6.1). Purified DAT possessed Km values of 6.5 microM and 1.3 microM for acetylcoenzyme A and deacetylvindoline, respectively, and Vmax values of 12.6 pkat/microgram protein (acetylcoenzyme A) and 10.1 pkat/micrograms protein (deacetylvindoline). Inhibition of DAT by tabersonine, coenzyme A, and cations (K+, Mg2+, and Mn2+) was observed, while the pH optimum of this enzyme was determined to be 7.5 to 9.
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PMID:Purification and characterization of acetylcoenzyme A: deacetylvindoline 4-O-acetyltransferase from Catharanthus roseus. 235 Jan 83

For the evaluation of differential diagnosis and estimation of the functional prognosis for vascular dementia (VD), the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) in detecting cerebro-vascular lesions was compared. Then the correlations between the degrees of mental function (Hasegawa's dementia rating scale: HDRS, activity of daily living: ADL, troublesome behaviors: TB) and the CT findings of vascular dementia were examined retrospectively. A hundred and seventeen dementia patients (male: 79 cases, female: 38 cases; mean-age 69.5 +/- 10.9 years old), diagnosed using DSM-III criteria, were scored according to Hachinski's ischemic score (I.S.) by clinical course and symptoms. Both MRI and CT were carried out on 56 dementia cases (male: 21 cases, female: 35 cases; mean-age 78.0 +/- 7.4 years old) at the chronic stage of the cerebro-vascular accidents to compare the detectiveness of vascular lesions. In 90 vascular dementia patients on whom only CT was carried out, the imagings were classified according to number, size, and localization. The correlation between these parameters and the degree of dementia were examined retrospectively. MRI was more useful and sensitive than CT for differentiating VD from DAT (dementia of Alzheimer type), since MRI was superior to CT in detecting small infarcts or lacunaes on the perforating area or white matter. Cases with positive findings on CT or MRI but clinically diagnosed as DAT by I.S. showed poorer ADL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A clinical study on the usefulness of CT and MRI imaging in evaluating differential diagnosis and the degree of dementia in vascular dementia]. 237 15

The purpose of the study was to determine whether oxiracetam crosses the human blood-brain barrier and to evaluate its comparative kinetics in serum and in cerebro-spinal fluid (CSF). Six DAT patients, undergoing CSF collection for diagnostic purposes, received 2 g oxiracetam daily, by a 60 min i.v. infusion, for 7 days. On the last day, in four patients blood samples were collected at time 0, 30, 60 and 120 min, and lumbar drainage was performed at the end of infusion: at this time mean CSF concentration was 3.5 micrograms/ml, i.e. 4.0% of the serum one, demonstrating that oxiracetam crosses the blood-brain barrier. In two patients, blood samples were collected at time 0, 60, 120 and 240 min, and lumbar drainage was performed 60 min after the end of infusion: at this time mean CSF concentration was 2.8 micrograms/ml, i.e. 5.3% of the serum one, indicating a persistence of oxiracetam within this deep compartment. These results provide the first evidence in humans that oxiracetam penetrates the central nervous system and contribute to the understanding of its long-lasting pharmacodynamic effect in man.
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PMID:Comparative kinetics of oxiracetam in serum and CSF of patients with dementia of Alzheimer type. 238 21

Methanol is a widely used solvent for organic compounds and a human toxicant. In our studies of the metabolism of aromatic amines in the Ames/Salmonella assay, we observed a rapid and quantitative conversion of the mutagenic and carcinogenic aromatic amine 2,4-diaminotoluene (2,4-DAT) to a single product. This product was only produced in the presence of methanol, and not other organic solvents. Isolation of this product showed that it was highly mutagenic in Salmonella TA98 with S9 activation. Characterization of the product of the interaction of methanol and 2,4-DAT indicated that methanol is activated to a reactive intermediate, probably formaldehyde, by the 9000 X g supernatant used in the Ames/Salmonella assay. The formaldehyde subsequently reacts with 2,4-DAT to form the mutagenic product, identified as bis-5,5'(2,4,2',4'-tetraaminotolyl)methane. Results of this study demonstrate that methanol may be an inappropriate solvent for mutation and metabolism studies of aromatic amines and possibly other chemicals, and that solvent-xenobiotic interactions may in some cases lead to the misinterpretation of results.
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PMID:The interaction of methanol, rat-liver S9 and the aromatic amine 2,4-diaminotoluene produces a new mutagenic compound. 238 42

Acetylcholine (ACh) and choline (Ch) in cerebrospinal fluid from 29 normal volunteers and 7 patients with Alzheimer-type dementia (DAT) were examined using high-performance liquid chromatography with electrochemical detector coupled with liquid cation-exchange method. In normal volunteers, ACh concentration was decreased significantly from 40-50 years and Ch concentration was increased significantly from 50-60 years. CSF from patients with DAT revealed high Ch concentration and the increase was statistically significant while ACh concentration in CSF of DAT did not show a significant difference with that of normal volunteers. This Ch augmentation may suggest a disturbance in utilization of Ch for ACh synthesis and may become an useful indicator for organic changes in central cholinergic system.
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PMID:Changes of acetylcholine and choline concentrations in cerebrospinal fluids of normal subjects and patients with dementia of Alzheimer-type. 239 14


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