Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002395 (Alzheimer's disease)
 110,584 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stopped-flow kinetic studies of the association of actinomycins with narural and synthetic DNA duplexes are presented. The actinomycins examined were D (C1), D lactam (in which the pentapeptide rings are closed by lactam instead of lactone linkages), X2, XObeta, and actinomine. The DNAs used included claf-thymus DNA, PM2, DNA, and two synthetic d(A-T)-lide copolymers containing 2,6-diaminopurine (DAP) in place of adenine residues, poly[d(DAP-T)]-poly[d(DAP-T)] and poly[d(DAP-A-T]-poly[d(DAP-A-T)]. Apparent equilibrium constants indicate that the DAP-containing polynucleotides bind actinomycin strongly. Comples formation of actinomycins D, D lactam, X2 and XObeta with these DNAs can be deconvoluted into five rate processes. These steps do not necessarily proceed to completion. The rates of two of these steps display a firstorder dependence on DNA concentration. The large negative entropies of activation of these steps suggest a high degree of restriction to freedom of motion on the respective transition states. The rates of the remaining three steps are independent of DNA concentration. Kinetic parameters of actinimycin binding to DNAs are presented and suggestions are made about some of the molecular evente believed to be responsible for the appearance of the five rate processes. For example, for DNA, poly[d(DAP-A-T)], and poly[d(DAP-T)], the observed order of apparent second-order rate constants, normalized to the concentration of actinomycin binding sites, suggests that binding of the antibiotic occurs most rapidly at binding sites (G-C of d DAT-T) near d(A-T) base pairs, where weakening of the double-helical conformation requires the least energy. Results obtained from studies of actinomycin D binding to heat-denatured poly[d(DAP-A-T)] and of actinomine and actinomycin D lactam binding to DNA suggest that the slow rate processes are related to an actinomycyl-pentapeptide-induced unwinding of the sugar-phosphate backbone of DNA accompanying insertion of the cyclic peptides into DNA.
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PMID:Stopped-flow kinetic studies of actinomycin binding to DNAs. 5 82

A number of DATS have been studied for agonist activity with dopamine (DA) and beta (beta) type adenylate cyclases and the most potent ones were found among the 6,7-DATs and the 5,6-DATs, respectively. None of the compounds tested possessed antagonist activity. The observed activities were not expected on the basis of structural analysis of model compounds such as apomorphine and 6,7-dihydroxy-1-benzyltetrahydroisoquinoline. A new view was constructed which suggests that the nitrogens of the DAT compounds were positioned better than those of the model compounds with regard to their binding sites.
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PMID:The effect of dihydroxy-2-aminotetraline (DATs) on dopamine and beta type adenylate cyclases. 20 26

In summary, the attrition rate for the recent dental school freshman classes has been reduced to 3 1/2 %. The national freshman enrollment of US dental schools can be expected to have approximately a 7% attrition rate by the time of graduation. The reasons for student withdrawal are evenly divided between personal and academic problems. The academic problems are experienced with slightly more frequency in nonclinical courses than in technique courses, both areas of difficulty being predicted significantly by DAT scores. Finally, the attrition rate for women is higher than for men, which has been true to a significant degree in the first-year classes during the past two years, as well as for all four years of dental school. However, no specific reason has been identified for this difference.
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PMID:Dental student attrition. 26 96

We have studied the activation of 2,4-diaminoanisole (2,4-DAA), a mutagenic hair-dye component, and 2,4-diaminotoluene (2,4-DAT), a hepatocarcinogen, to products which blind covalently to tissue macromolecules. Four hours after a dose of 100 mg/kg ring-labeled 3H-2,4-DAA, 0.30 nmol is found covalently bound per mg liver protein. This amount is increased by 83% after phenobarbital pretreatment, and by 43% after beta-naphthoflavone-pretreatment. Almost the same degree of binding is seen in kidneys. Subcellular fractionation of livers shows that most of the bound material is in the microsomal fraction. Similar levels of covalent protein binding is seen after administering ring-labeled 3H-2,4-DAT. No significant binding to DNA in vitro or in vivo could be demonstrated using 3H-2,4-DAA or 3H-2,4-DAT, whereas 3H-2,4-DAT is found to covalently bind to hepatic RNA.
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PMID:Covalent binding of 2,4-diaminoanisole and 2,4-diaminotoluene in vivo. 27 4

One hundred patients were entered in a cooperative study comparing the efficacy of two different regimens in the induction treatment of acute nonlymphocytic leukemia (ANLL). Patients were randomly allocated to receive either the DAT or VAT combination; half of the patients were also randomized to receive CNS prophylaxis including intrathecal methotrexate + prednisone and cranial irradiation. Consolidation and maintenance therapy were uniform in responding patients. Out of 82 evaluable patients 41 (50%) attained complete remission (CR) with no significant difference between the two regimens. Median remission duration was slightly longer in the DAT group (32.5 vs 22 weeks); median survival was 34 weeks for all evaluable patients with no difference between the two schedules. Meningeal relapse occurred only in two patients after 19 and 99 weeks of continuous remission. Fourteen patients are still alive after 61 to greater than or equal to 155 weeks, of whom seven are in their initial remission (six in the DAT and one in the VAT group). We conclude that 1) DAT and VAT are equally effective in inducing CR in a high proportion of ANLL patients; 2) until marrow remission can be prolonged significantly, preventing CNS leukemia will not have any significant impact of the course of ANLL.
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PMID:Daunomycin, cytosine arabinoside and 6-thioguanine (DAT) vs vincristine, cytosine arabinoside and 6-thioguanine (VAT) in the induction treatment of acute nonlymphocyte leukemia: a randomized collaborative study. 27 49

Admission into dental faculties is based on preprofessional average, prerequisite average, and DAT scores among other criteria. This study investigated the predictive validity of these variables on success in the Faculty of Dentistry at the University of British Columbia. Data on 312 students admitted between 1969 and 1976 were subjected to multiple regression analyses. Results showed that overall preprofessional average significantly correlated .17 to .29 with nine first- and second-year course grades, .36 with first-year average, and .29 with second-year average. DAT manual average correlated significantly with five course grades from .20 to .36, .20 with second-year average, and .30 with third-year average grades. Chalk carving correlated significantly .20 to .40 with five course grades and .24 with third-year average. It is recommended that overall average and chalk carving be given equal emphasis in the selection process.
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PMID:Grade averages and DAT scores as predictors of performance in dental school. 29 Jun 64

Of 71 patients showing a negative direct antiglobulin (Coombs') test (DAT) before administration of cephalexin (CEX) three developed a positive DAT after therapy with this drug (4 percent). No case of immunohemolytic anemia was observed. The sera of the patients with a positive DAT reacted with cephalothin-coated red cells producing high titers, with penicillin cells normal titers and with CEX cells low titers. Since the red cell eluates of these patients did not give significant reactions with red cells sensitized with CEX, cephalothin and penicillin, a nonimmunological mechanism for the development of the positive DAT in these patients has to be assumed.
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PMID:Positive direct antiglobulin (Coombs') test caused by cephalexin administration in humans. 80 37

We are herein submitting the results obtained with a group of 13 nonmongoloid, oligophrenic children after 180 days' treatment with DAT, and we have compared the results with those of a control group that received only conventional treatment. The children were examined before and after the treatment by means of the Binet-Simon tests, which have been standardized by Kuhlmann, and the Wise and Terman Merrill test. The control of organic lesion was determined by the Bender test. The variation mean of the control group was 0.08, and that of the DAT-treated group was 0.954; 0.874 was the mean difference, and 0.543 and 1.205 were the degrees of reliability. The difference between the results obtained from the DAT-treated group and the one that received conventional medication was significant (P equal 0.01). None of the 13 cases treated showed any signs of toxicity.
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PMID:Dimethyl sulfoxide therapy in nonmongoloid infantile oligophrenia. 109 64

During a 3-year period we observed 5 patients who developed IHA after transplantation of solid organs (4 kidneys, 1 liver) due to irregular anti-erythrocyte antibodies of donor origin (4 times anti-D, once anti-D+C). The onset of acute haemolysis was usually within 2-3 weeks after transplantation; however, 1 patient developed acute haemolysis as late as day 116 after renal transplantation. The course of the clinical and serological signs (DAT positive, 'auto'-antibodies in serum and eluate) was typical and self-limited in all cases, the function of the transplanted organ was usually not affected. All patients could be managed by transfusion of antibody-compatible blood. The administration of azathioprine (1 case) did not seem to have any beneficial effect. The causative antibodies could be demonstrated retrospectively in the serum of 1 donor. Another donor had no detectable irregular anti-erythrocyte antibodies at the time of transplantation, suggesting a secondary immune response of transplanted lymphatic tissue in this case. Both recipients of a kidney from this donor developed IHA. Serum samples of the 2 other donors were not available for investigation. We suggest that a sensitive screening for irregular anti-erythrocyte antibodies in the donor's serum should be performed before any transplantation of solid organs. If such antibodies are found, organs should only be used after irradiation. However, as our experiences show, this cannot prevent IHA in each case. Once haemolysis develops, the correct serological diagnosis and the transfusion of antibody-compatible red blood cells are most important.
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PMID:Immune-haemolytic anaemia (IHA) after solid organ transplantation due to rhesus antibodies of donor origin: report of 5 cases. 128 36

Cerebral hemorrhages with amyloidosis and dementia of the Alzheimer type have many neuropathological findings in common, but there are also marked quantitative and qualitative differences. That makes it highly improbably that the B-protein amyloid depositions itself are the direct cause of extensive neuronal death and dementia in DAT.
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PMID:Neuropathological findings in cerebral B-protein amyloidosis. Differences and similarities in those cases presenting as a cerebral hemorrhage and those presenting as a dementia of the Alzheimer type. 132 May 18


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