Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease

In this study, hyperpolarized ¹²⁹Xe MR ventilation and ¹H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age‐matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader‐based ventilation defect score percentage (VDS%) and a semi‐automated segmentation‐based ventilation defect percentage (VDP). Reader‐based values were assigned by two experienced radiologists and resolved by consensus. In the semi‐automated analysis, ¹H anatomical images and ¹²⁹Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader‐based VDS% correlated strongly with the semi‐automatically generated VDP (r = 0.97, p < 0.0001) and with CV (r = 0.82, p < 0.0001). Both ¹²⁹Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1 s (FEV₁) (VDS%: r = –0.78, p = 0.0002; VDP: r = –0.79, p = 0.0003; CV: r = –0.66, p = 0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r = 0.61, p = 0.0002; VDP: r = 0.63, p = 0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns. Copyright © 2012 John Wiley & Sons, Ltd.     

Impact of 3′UTR variation patterns of the KRAS gene on the aggressiveness of pancreatobiliary tumors with the KRAS G13D mutation in a Turkish population

ObjectiveSeveral studies have demonstrated the importance of mutations in codons 12, 13 and 61 and variations in the 3′ untranslated region (3′UTR) of the KRAS gene, frequently observed genetic events in the progression of pancreatobiliary tumors (PBT). However, limited data exist on the clinical effect of these alterations. The aim of the current study was to clarify the frequency of relevant alterations of the 3′UTR regions of the KRAS gene and the effect of KRAS 3′UTR polymorphisms on the prognosis of patients with codon 12, 13 and 61 mutations in a Turkish population with PBT.MethodsCodons 12, 13, and 61 and 3′UTRs of the KRAS gene were screened by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing in 43 patients and 10 controls. Chi-squared and independent sample T tests were used to evaluate the results of the mutation analysis and clinical features of the patients.ResultsWe defined the c.38G > A (rs112445441, p.G13D) (39.54%) mutation and two 3′UTR variations, c.*4066delA (rs560890523) (23.26%) and c.*4065_*4066delAA (rs57698689) (6.98%), in the KRAS gene of Turkish patients. There was a statistically significant relationship between the c.*4066delA (rs560890523) and c.*4065_*4066delAA (rs57698689) variations and invasion and lymph node metastasis status of the patients (p < 0.001). Compared to patients with c.38G > A (rs112445441, p.G13D), patients with c.*4066delA (rs560890523) and c.38G > A (rs112445441, p.G13D) presented more aggressive tumors with highly invasive features. The present study contributes findings regarding the clinical effects of KRAS alterations in PBT. Based on our study, further investigations are required.     

Hyperpolarized 129Xe MRI using isobutene as a new quenching gas

The use of a quenching gas, isobutene, with a low vapor pressure was investigated to enhance the utility of hyperpolarized ¹²⁹Xe (HP Xe) MRI. Xenon mixed with isobutene was hyperpolarized using a home‐built apparatus for continuously producing HP Xe. The isobutene was then readily liquefied and separated almost totally by continuous condensation at about 173 K, because the vapor pressure of isobutene (0.247 kPa) is much lower than that of Xe (157 kPa). Finally, the neat Xe gas was continuously delivered to mice by spontaneous inhalation. The HP Xe MRI was enhanced twofold in polarization level and threefold in signal intensity when isobutene was adopted as the quenching gas instead of N₂. The usefulness of the HP Xe MRI was verified by application to pulmonary functional imaging of spontaneously breathing mice, where the parameters of fractional ventilation (r_a) and gas exchange (f_D) were evaluated, aiming at future extension to preclinical studies. This is the first application of isobutene as a quenching gas for HP Xe MRI.     

Gonadectomy alters myosin heavy chain composition in isolated cardiac myocytes

A total of 95 patients with Graves’ disease (GD) and 105 normal healthy controls were enrolled in this study to determine how a single site polymorphism of the transporter associated with antigen processing 1 (TAP1) gene contributes to the pathogenesis of GD. The polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. Associations between GD and the two-site polymorphisms of the TAP1 gene at codons 333 and 637 were evaluated. No significant differences were revealed comparing GD patients and normal individuals for the distributions of genotypes and allelic variants at codon 333 (p=0.253 and p=0.891, respectively). By contrast, the distributions for the AA homozygote at codon 637 were reduced and those for the GA heterozygote were increased comparing the two groups (p<0.0001). The allelic analysis also demonstrated lower A and higher G allele frequencies (p=0.0008; OR=2.745, 95% CI=1.482-5.085) comparing the GD patients with the normal healthy controls. This shows that the single-site polymorphism of the TAP1 gene at codon 637 may be an indicator for predicting development of GD.     

Evolutionary characterization of Tembusu virus infection through identification of codon usage patterns

Tembusu virus (TMUV) is a single-stranded, positive-sense RNA virus. As reported, TMUV infection has resulted in significant poultry losses, and the virus may also pose a threat to public health. To characterize TMUV evolutionarily and to understand the factors accounting for codon usage properties, we performed, for the first time, a comprehensive analysis of codon usage bias for the genomes of 60 TMUV strains. The most recently published TMUV strains were found to be widely distributed in coastal cities of southeastern China. Codon preference among TMUV genomes exhibits a low bias (effective number of codons (ENC) = 53.287) and is maintained at a stable level. ENC-GC3 plots and the high correlation between composition constraints and principal component factor analysis of codon usage demonstrated that mutation pressure dominates over natural selection pressure in shaping the TMUV coding sequence composition. The high correlation between the major components of the codon usage pattern and hydrophobicity (Gravy) or aromaticity (Aromo) was obvious, indicating that properties of viral proteins also account for the observed variation in TMUV codon usage. Principal component analysis (PCA) showed that CQW1 isolated from Chongqing may have evolved from GX2013H or GX2013G isolated from Guangxi, thus indicating that TMUV likely disseminated from southeastern China to the mainland. Moreover, the preferred codons encoding eight amino acids were consistent with the optimal codons for human cells, indicating that TMUV may pose a threat to public health due to possible cross-species transmission (birds to birds or birds to humans). The results of this study not only have theoretical value for uncovering the characteristics of synonymous codon usage patterns in TMUV genomes but also have significant meaning with regard to the molecular evolutionary tendencies of TMUV.