Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ts CB1200 (antimutator) mutation in bacteriophage T4 DNA polymerase increases the accuracy of DNA replication since it results in a decrease in the frequency of mutations in other phage genes. The CB120 polymerases differs from the wild type enzyme in the slow rate at which it copies templates where primer extension requries displacement of polynucleotides base-paired to the template strand, even in the presence of the T4 DNA unwinding protein (gene 32-protein). The ratio of nucleotides turned over (DNA-dependent conversion of deoxynucleoside triphosphate to deoxynucleoside monophosphate) to nucleotides stably incorporated into product is 10 to 100 times higher with the mutant than wild type enzyme, depending on the DNA used as the template. This high turnover rate may increase the efficiency of removal of noncomplementary nucleotides by the antimutator enzyme and is in agreement with the findings of Muzyczka et al, (Muzyczka, N., Poland, R. L., and Bessman, M. J. (1972) J. Biol, Cehm. 247, 7116-7122) with the L141 and L42 antimutator T4 DNA polymerases. Since the 3'- to 5'-exonuclease activity of the CB120 mutant polymerase is not higher than that of the wild type enzyme, it is suggested that the high turnover rate may result from increased opportunity to remove newly incorporated nucleotides due to the slow rate at which the mutant enzyme moves to the next template nucleotide. In the accompanying paper we show that the CB120 antimutator polymerase also initially selects incorrect nucleotides for incorporation less frequently than the wild type enzyme. Thus this antimutator polymerase appears to have both greater accuracy in nucleotide selection and an enhanced ability to remove incorrect nucleotides.
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PMID:Control of mutation frequency by bacteriophage T4 DNA polymerase. I. The CB120 antimutator DNA polymerase is defective in strand displacement. 95 82

Efficacity of tiniba (tinidasole, Kadila, India) and of fasigyn (Polfa, Poland) dosed 300 mg daily for 7 days was 87.5 and 85.2% (P greater than 0.05) immediately after treatment and 45.5 and 50.0% (P greater than 0.05) 4-8 months later, respectively. The lack of parasitocidal effect was established in 4 out of 27 tiniba-treated patients and in 3 out of 24 fasigyn treated ones. Direct correlation between the efficacy of persisting giardia infection chemotherapy and the cAMP phosphodiesterase activity in blood lymphocytes was found previously. Authors established an indirect correlation between the former and hydrochloric acid secretion by the bowel.
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PMID:[Comparative efficacy of tiniba and fasigyn in treating primary and persisting Giardia infections]. 254 42

The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes (odds ratio for the G-allele, 0.85 [95% CI 0.78-0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42-0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes.
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PMID:Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity. 1706 59

Pulmonary arterial hypertension (PAH) is a chronic, serious disease caused by remodeling of small pulmonary vessels, which leads to increase of pulmonary resistance, right heart failure and death. The 1990ths of XX century are the beginning of dynamic research into the pathophysiology and treatment of this disease. Actually, the goal oriented therapy based on three main metabolic pathways includes: prostacyclin's analogues, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Applying this therapy, according to ESC guidelines has prolonged significantly the survival in the group of patients with PAH. Due to the high cost of the therapy, there has been created the national therapeutic program in Poland. It assures the real possibility of therapy for patients with PAH from the third FC WHO.
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PMID:[The current pharmacotherapy of pulmonary arterial hypertension]. 2576 86