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)

This retrospective study was undertaken to analyse the survival pattern of 118 consecutive, unselected patients with acute myelogenous leukemia (AML) aged between 60 and 82 years observed at a single centre over a 10-year period (1981-1991). Thirty-two per cent of cases had an antecedent hematological disorder (AHD), and 7 per cent had a secondary AML. Forty patients (39 per cent) were managed with palliative intent with short courses with oral hydroxyurea +/- 6-thioguanine. In contrast to 78 patients (61 per cent) selected for remission-induction treatment, these were significantly older (P < 0.0001), had a greater incidence of AHD (P < 0.039) and of hypoplastic AML (P < 0.017), and an inferior amount of blast cells in the bone marrow (P < 0.003). Patients undergoing remission-induction chemotherapy were managed with DAT-like chemotherapy, high-dose cytosine arabinoside (HD-ara-C), and mitoxantrone-based regimens. The complete response (CR) rate was 29 per cent. Response was higher with the two most intensive HD-araC and mitoxantrone-etoposide-araC programmes (P < 0.026), and correlated favourably with no AHD (P < 0.04) and lower blast cell count in the peripheral blood (P < 0.02). Overall survival of responders was longer than in palliation and nonresponder groups (P < 0.025 and P < 0.001, respectively). In the active treatment group, survival correlated with performance status (P < 0.005) and blast cell count (P < 0.05). Infection was the main cause of morbidity during active treatment, accounting for most induction failures (60 per cent), followed by haemorrhage (12 per cent) and resistant disease (12 per cent). These results from an unselected series represent an improvement over those obtained by us in previous years (1971-1980), and show that intensive treatment programmes are applicable to the elderly with AML and that prolonged disease-free survival is possible for some. Improving further CR rate and duration will depend equally on the optimization of supportive care measures and the introduction of more effective therapeutic modalities.
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PMID:The management of acute myelogenous leukemia in the elderly: ten-year experience in 118 patients. 149 9

An objective scale for measuring discomfort in noncommunicative patients with advanced Alzheimer's disease was empirically generated from the perspectives of nursing staff practicing on special care Alzheimer units and was judged to have content validity. On the basis of a pilot test, the discomfort scale was reduced to nine items. Quantifiable scoring procedures and a rater training program were developed. The scale (DS-DAT) was tested longitudinally for 6 months with 82 subjects at two sites. Psychometric properties, measurement issues, and recommendations for use in practice and research are discussed.
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PMID:Assessment of discomfort in advanced Alzheimer patients. 152 21

The antiemetic effects of a novel serotonin3 receptor antagonist, DAT-582 [(6R)-(-)-N-[1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4- diazepin-6-yl]-1H-indazole-3-carboxamide dihydrochloride] were compared with those of the existing serotonin3 receptor antagonists, ondansetron and granisetron, in experimental animals. In ferrets, DAT-582 (0.003-0.1 mg/kg i.v. twice) dose-relatedly prolonged the latency to the first emetic episode and decreased the number of emetic episodes induced by cisplatin (10 mg/kg i.v.). DAT-582 was more potent than ondansetron or granisetron in inhibiting the emesis. The emesis induced by cyclophosphamide (150 mg/kg i.v.), doxorubicin (15 mg/kg i.v.) or combination of cisplatin (3.3 mg/kg i.v.), cyclophosphamide (50 mg/kg i.v.) and doxorubicin (5 mg/kg i.v.) was also inhibited by DAT-582 (0.1 mg/kg i.v., twice). When administered 2 hr before cisplatin in ferrets, DAT-582 decreased markedly the number of emetic episodes induced by cisplatin at 0.1 mg/kg i.v., whereas ondansetron and granisetron were without effect even at 0.3 mg/kg i.v. DAT-582 (0.1 mg/kg i.v.), when administered in the ferrets which were vomiting after cisplatin, immediately and almost completely blocked the subsequent emesis. Furthermore, DAT-582 (0.1 mg/kg i.v.) completely inhibited the cisplatin (3 mg/kg i.v.)-induced emesis for 24 hr after cisplatin in three of five dogs. In addition, DAT-582, at 0.3 and 1 mg/kg, p.o., inhibited the cisplatin-induced emesis in dogs. However, DAT-582, even at 3 mg/kg s.c., did not inhibit the apomorphine (0.3 mg/kg,, s.c.)-induced emesis in dogs, or the nicotine-, copper sulfate- or motion stimulus-induced emesis in the house musk shrew, Suncus Murinus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DAT-582, a novel serotonin3 receptor antagonist, is a potent and long-lasting antiemetic agent in the ferret and dog. 153 32

Although visuoconstructive impairment has been reported in both Alzheimer's (DAT) and Huntington's (HD) disease, there is little knowledge concerning how this cognitive deficit differs quantitatively and qualitatively in these two progressive dementias. To address this issue, the present study compared performances on the Clock Drawing Test (CDT: command and copy) of 25 DAT patients, 25 equally demented HD patients, and 25 elderly normal controls (NC). In the command condition, both patients groups were significantly impaired compared to the NC group. Although there was no significant difference between DAT and HD patients' total quantitative scores, a qualitative error analysis revealed a number of dissociations between the two patient groups. Graphic difficulties, very common in HD patients, were virtually absent in DAT patients; in contrast, conceptual errors were almost exclusively seen in DAT patients and were related to the severity of their dementia. Perseveration and "stimulus-bound" responses were also more frequent in DAT patients, and both groups made visuospatial errors. In the copy condition, the DAT, but not the HD, patients evidenced a marked improvement in performance. These results indicate that while both DAT and HD patients have significant visuoconstructive difficulties even in the early stages of their disorders, the specific cognitive processes underlying their quantitative impairments are quite different. It is possible that the DAT patients' conceptual errors are yet another indicator of the deterioration of their semantic knowledge.
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PMID:Quantitative and qualitative analyses of clock drawings in Alzheimer's and Huntington's disease. 154 77

Cross-correlation (CCT) and dip analysis (DAT) are accepted techniques for estimating muscle fiber conduction velocity (MFCV). In the DAT, the product of the power spectrum of the conducted EMG times a cosine function of the MFCV is added to and inseparable from the noise power spectrum. The inclusion of the noise power is the weakness of the DAT. We propose and evaluate 2 new techniques that directly estimate the cosine function and, hence, the MFCV, avoiding the noise power: (1) The power-modulating-component (PMC), which equals the real part of the cross-power-spectrum of the EMG signal divided by its magnitude; and (2) The power spectrum of the PMC (PMCP). We recorded intramuscular from 229 biceps in isometric maximum voluntary contraction. The EMG signals were analyzed by the 4 techniques, and the results were compared in pairwise design (sign-tests and t tests) for quality and bias. The PMC surpassed the DAT (P less than 0.00005); both the CCT and PMCP performed equally well and better than the DAT and the PMC (P less than 0.00005). Also, the new techniques were superior with simulated EMG. In many cases only the PMCP worked. We conclude that the new techniques are valuable in supplementing the others, and most likely will enhance clinical use of MFCV estimations.
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PMID:Improved techniques for measuring muscle fiber conduction velocity. 155 92

2,4-Diaminotoluene (2,4-DAT), a high volume synthetic compound, is moderately carcinogenic to rodents. We report here that 2,4-DAT is a substrate for the peroxidase activity of prostaglandin H synthase (PHS). In contrast to many aromatic amines which are activated as mutagens by PHS, we find that 2,4-DAT is not mutagenic to six S. typhimurium strains with this activation system. The strains tested include YG1006, YG1024, and YG1029, which are far more sensitive to the mutagenicity of aromatic amines and nitroarenes than are the standard tester strains. Although not mutagenic itself, 2,4-DAT does enhance the mutagenicity of 2-aminofluorene (2-AF) in the PHS-catalyzed system in strains TA98, YG1006, and YG1024, with maximal enhancement of 140%, 1831%, and 1216%, respectively. Half-maximal enhancement of 2-AF mutagenicity is observed at 15-20 microM 2,4-DAT for strains YG1006 and YG1024, and about 80 microM for TA98. Studies with compounds structurally related to 2,4-DAT revealed enhancement of 2-AF mutagenicity with 2,5-DAT and o-phenylenediamine (o-PD) but not for other DAT isomers, toluidines, and phenylenediamines. Maximal enhancement of 2-AF mutagenicity observed in TA98 with PHS-catalyzed activation was 110% for o-PD and 60% for 2,5-DAT. This comutagenic effect of 2,4-DAT appears quite specific for 2-AF, as it fails to enhance either the PHS-dependent mutagenicity of the aromatic amines benzidine and 2-naphtylamine, or the direct mutagenicity of N-acetoxy-acetylaminofluorene,2-nitrofluorene,4- nitroquinoline-N-oxide and 1,1,1-trichloropropene-2,3-oxide. Enhancement of 2-AF mutagenicity by 2,4-DAT is also observed with cytochrome P-450-dependent activation, however the half-maximal 2,4-DAT concentration was 400 microM, and the maximal enhancement was only 50%. The ability of 2,4-DAT, under conditions where it is not itself mutagenic, to enhance the genotoxicity of the potent carcinogen 2-AF comprises an intriguing toxicological interaction, and underscores the inherent difficulties in assessing the genotoxic risks posed by mixtures of compounds.
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PMID:Prostaglandin H synthase-dependent genotoxicity of 2,4-diaminotoluene. 157 43

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.
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PMID:Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group. 157 10

In a double blind randomized crossover trial lasting 6 months selegiline, a selective MAO-B inhibitor, was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia (DAT). Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment, at the time scheduled for crossover (90 days) and at the end of the trial (180 days). The results suggest that selegiline possesses significant activity on some memory parameters, which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisition.
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PMID:Alzheimer-type dementia and verbal memory performances: influence of selegiline therapy. 159 75

This article reviews the syndromic concepts of depression and dementia and the concurrence of these common entities. In DAT, depression appears to be a reversible source of excess disability, amenable to pharmacologic as well as environmental interventions. In the vascular dementias, depression appears to be a specific complicating feature, in which localization of the lesion plays a significant role. The abulic state should not be mistaken for a depressive syndrome, although its presence should alert the clinician to evaluate for dementia and depression. Depression is especially prevalent in the subcortical dementias. Future studies using dynamic neuroimaging will help define the limits of this important concept. Reversible forms of dementia are much less common than previously suspected. The clinician's task is to identify causes of excess disability due to superimposed illnesses while avoiding diagnostic or therapeutic nihilism. The appropriate use of medication and the ongoing surveillance for adverse drug reactions are the foremost tasks of today's clinician treating the elderly patient.
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PMID:Depression, dementia, and reversible dementia. 160 Apr 79

A 54 y.o. woman presented with acute Coombs-negative hemolytic anemia at an outside hospital where she received 25 RBC transfusions and did not respond to prednisone or splenectomy. On transfer to our hospital, routine DAT and IAT were weakly positive, occasionally negative. When a modified "cold" antiglobulin test was employed, the result was strongly positive for IgG, weakly positive for C3d. Cold agglutinin titer was 32, and the Donath-Landsteiner test was negative. The autoantibody exhibited Pra specificity. The patient failed IV-IgG, high dose IV pulse steroids and cyclophosphamide, and continued to require daily transfusions. She responded 21 days after receiving daily plasma exchange (x3), with pulse cyclophosphamide on the third day, followed by escalating daily oral cyclophosphamide.
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PMID:Refractory immune hemolytic anemia with a high thermal amplitude, low affinity IgG anti-Pra cold autoantibody. 161 12


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