Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia.

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1-9 and 11-12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1-10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance.

DFT investigation of role of N - H⋯O and N - H⋯π interactions in the stabilization of the hydrogen bonded complexes of anisole with aromatic amines.

Theoretical investigations have been performed on hydrogen (H-) bonded complexes of two aromatic amines with anisole to investigate the effect of the methyl substituent on N - H⋯O and N - -H⋯π interactions. Natural bond orbital (NBO) and quantum theory of atoms in molecules (QTAIM) analyses were done to elucidate the nature of H- bonding. In 1:1 complexes, the total interaction energy of N-methylaniline complex is higher than that of aniline complex. The existence of bond critical point between N-H of amine and oxygen of anisole confirms weak hydrogen bonding. The energy decomposition analysis showed the role of CT in stabilizing complexes.

Circadian rhythmicity of plasma lipid peroxidation and antioxidants in oral squamous cell carcinoma.

INTRODUCTION: Oral cancer is one of the leading cancers in India accounting for 30 to 40 percent of all cancers. Disturbances in lipid peroxidation and antioxidants status have been implicated in the pathogenesis of several cancers including oral cancer. However, circadian disturbances of oxidants and antioxidants in oral cancer patients were not reported. METHODS: The levels of plasma thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and activity of glutathione peroxidase (GPx) in ten oral cancer patients and an equal number of age-matched healthy subjects were assayed at every 6 hour intervals using colorimetric methods and their circadian characteristics were analysed using Cosinorwin computer software programme. RESULTS: Alterations in mesor, amplitude, acrophase and r value of the chosen parameters were noticed. DISCUSSION: The desynchronisation of plasma thiobarbituric acid reactive substances and the altered circadian characteristics of antioxidants observed in this study, may deserve further investigation for the early diagnosis, prognosis and for the efficacy of cancer chronotherapy.

Temporal changes in prevalence of diabetes and impaired glucose tolerance associated with lifestyle transition occurring in the rural population in India.

AIMS/HYPOTHESIS: The rural Indian population is undergoing lifestyle transition due to socio-economic growth. This study was done to determine the temporal changes in prevalence of diabetes and IGT that could have occurred in a rural population in India as a result of the lifestyle transition. METHODS: A cross-sectional study of 1213 Asian-Indian subjects aged 20 years or over was done to look for the prevalence of diabetes and IGT using the 1999 WHO criteria. The temporal changes were assessed in comparison with a similar study conducted 14 years previously. The factors associated with the temporal changes were also analysed. RESULTS: Nearly a three-fold increase in age- and sex-adjusted prevalence of diabetes (from 2.20% to 6.36%) was seen in 2003 when compared with a similar study done 14 years before. Prevalence of IGT did not change significantly (7.44% in 1989 vs 7.18% in 2003). Improvement in living conditions had occurred during the period, occupational changes were seen, the number of manual labourers had decreased and economic conditions had improved. BMI and waist circumference had increased. After correcting for age, sex and differences in time periods, waist circumference and physical inactivity showed significant associations with the increased prevalence of diabetes. CONCLUSIONS/INTERPRETATION: Demographic transition due to improved living conditions in rural India was associated with a three-fold increase in the prevalence of diabetes. Increased upper body adiposity and physical inactivity showed significant association with this phenomenon.