ABSTRACT
Cytidine deaminase (MtCDA), encoded by cdd gene (Rv3315c), is the only enzyme identified in nucleotide biosynthesis pathway of Mycobacterium tuberculosis that is able to recycle cytidine and deoxycytidine. An M. tuberculosis knockout strain for cdd gene was obtained by allelic replacement. Evaluation of mRNA expression validated cdd deletion and showed the absence of polar effect. MudPIT LC-MS/MS data indicated thymidine phosphorylase expression was decreased in knockout and complemented strains. The cdd disruption does not affect M. tuberculosis growth both in Mid- dlebrook 7H9 and in RAW 264.7 cells, which indicates that cdd is not important for macrophage invasion and virulence.
Subject(s)
Humans , Cytidine Deaminase/genetics , Deoxycytidine/genetics , Macrophages/microbiology , Mycobacterium tuberculosis/pathogenicity , Time Factors , Cytidine Deaminase/biosynthesis , Deoxycytidine/biosynthesis , Gene Knockout Techniques , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/enzymologyABSTRACT
No abstract available.
Subject(s)
Aged , Humans , Male , Cytidine Deaminase/genetics , Dasatinib/therapeutic use , Disease Progression , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl/genetics , Imatinib Mesylate/therapeutic use , In Situ Hybridization, Fluorescence , Karyotype , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Microfilament Proteins/genetics , Oncogene Proteins/genetics , Protein Kinase Inhibitors/therapeutic useABSTRACT
Single nucleotide polymorphisms [SNPs] of deoxyctidine kinase [dCK] and cytidine deaminase [CDA] are known to alter their enzymatic activities, which affect the metabolism of cytarabine. Currently, treatment of childhood acute lymphoblastic leukemia [ALL] includes cytarabine, especially in high-risk patients. Therefore we hypothesized that a genetic variation of dCK and CDA genes may influence the risk of cytarabine-related toxicities and early response to treatment. We included children diagnosed with ALL and lymphoblastic lymphoma [LL] stage III and IV. The patients received a modified ST Jude Total Therapy Study XV protocol. Cytarabine was used during induction remission [low-dose cytarabine] and reinduction II [high-dose cytarabine] phases. Genotyping of dCK -360 > G and -201 > T and CDA 79A > C and 208G > A was performed. Minimal residual disease [MRD] at the end of the induction phase was measured using flow cytomery. Ninety-four children with ALL [n=90] and LL [n=4] were analyzed. The median age at diagnosis was 5.8 years [range, 0.4-15 years]. All four SNPs showed predominant wild type alleles. There was no CDA-208A allele in our population. Children with dCK-360G allele were at risk of mycositis after receiving low-dose cytarabine [OR=3.7; 95% CI, 1.2-11.3]. Neither dCK nor CDA polymorphisms affected the MRD status at the end of induction phase. The dCK-360G allele was found to found to increase the risk of mucositis after expose to low-dose cytarabine in childhood ALL therapy
Subject(s)
Humans , Male , Female , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Deoxycytidine Kinase/genetics , Cytidine Deaminase/genetics , Genotype , ChildABSTRACT
The relationship between 3 polymorphisms sites [interleulin-4 (IL-4), IL-4 receptor (IL-4R) alpha chain and activation-induced cytidine deaminase (AICDA)] and adult allergic asthma in China was studied. By using case-control method, DNA and clinical data were obtained from allergic asthmatic patients and compared with those in the control subjects. The subjects were genotyped for the IL-4 C-589T promoter polymorphism, the IL-4R alpha chain Q576R and the AICDA C8408T by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results showed that the IL-4 C-589T was not associated with adult allergic asthma in China. However, the IL-4R alpha chain 576R/R and AICDA 8408T/T frequency was significantly increased in allergic asthma group as compared with that in the control group [odd ratio (OR) = 3.797 and 9.127, respectively; P < 0.01)] and was correlated with the increased plasma total IgE. These data suggested that the IL-4R alpha chain 576R/R and AICDA 8408T/T genotypes confer genetic susceptibility to adult allergic asthma in China.