CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis

Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P.aeruginosa was subsequently isolated (492.75 μg/ml vs. 1339.43 μg/ml, p = 0.018). Those with the CD14 -159CC genotype had a significantly increased risk of early infection with P.aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P.aeruginosa.     

Transcriptomic response to differentiation induction

Background  

Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes.     

Coordination in gene expression during atherogenesis

General tendencies in the regulation of gene expression during atherogenesis were investigated using correlation analysis for 34 mRNA species of several functional groups. The contents of mRNA were measured by quantitative PCR in samples of human aortal intima containing no lesions or atherosclerotic lesions of types I (initial lesions), II (fatty streaks), and Va (fibroatheromas). The coupling between mRNA contents in lesions and the same mRNAs in intact tissue was found to descend in the course of the disease progression. The data are in accordance with the opinion that successive morphologic types of atherosclerotic lesions correspond to steps of atherogenesis. In addition, the contents of individual mRNA species could correlate with each other within the given sample type, the extent of this coupling rising along with the disease progression. The exception from this rule was a collapse in coupling for several functional groups of mRNA in lesions of type I. This collapse could indicate special position of these lesions in pathogenesis. Statistically significant correlations between mRNAs found in samples of all four types comprised in total about 50% of all possible correlations. 66% of these correlations were conservative, i.e. observed in at least two sample types. By coupling-strength, the studied mRNAs could be divided into four clusters whose composition significantly varied along with the disease progression. The disease progression was also associated with decline in number of regulatory factors that determine coordination in expression of the analyzed genes.     

Association of Mitochondrial Genetic Variation with Carotid Atherosclerosis

In human pathology, several diseases are associated with somatic mutations in the mitochondrial genome (mtDNA). Even though mitochondrial dysfunction leads to increased oxidative stress, the role of mitochondrial mutations in atherosclerosis has not received much attention so far. In this study we analyzed the association of mitochondrial genetic variation with the severity of carotid atherosclerosis, as assessed by carotid intima-media thickness (cIMT) and the presence of coronary heart disease (CHD) in 190 subjects from Moscow, Russia, a population with high CHD occurrence. cIMT was measured by high-resolution B-mode ultrasonography and mtDNA heteroplasmies by a pyrosequencing-based method. We found that heteroplasmies for several mutations in the mtDNA in leukocytes, including C3256T, T3336C, G12315A, G13513A, G14459A, G14846A, and G15059A mutations, were significantly (p<0.001) associated with both the severity of carotid atherosclerosis and the presence of CHD. These findings indicate that somatic mitochondrial mutations have a role in the development of atherosclerosis.