Booth Delgado (nodecd5)

The Mutation I1234V is a CF causing mutation; however the mechanisms leading to loss of function are not fully understood. In this study, we aimed to characterize phenotypically individuals with the I1234V variant, and to gain a structural point of view of the mutant CFTR using computational studies. We conducted a retrospective descriptive study, reviewing the clinical records of 9 Israeli patients. The study was designed to include patients either homozygous or compound heterozygous for the I1234V mutation. For a comparison we analyzed clinical data of 12 patients homozygous for the F508del mutation. learn more Computer models were constructed for I1234V, 1234-1239del and wild type CFTR. Mean FEV1 was 73.8±21% predicted with an average annual rate of decline of 1%. When compared to patients homozygous for F508del the mean annual values of FEV1% predicted during the 6 years of data collection ranged from 51 to 58±22-30 in the F508del group versus 76-82±14-19 in the I1234V group (p<0.05). Structural models did not demonstrate noticeable differences between the three simulated constructs. Although the mutation resides in the NBD2, no interference with ATP binding was detected. This study describes phenotypically patients carrying the I1234V mutation. Compared to patients homozygous for F508del, these patients present with more favorable outcome. Structural models show high similarity between the static and dynamics pictures obtained for both the mutated and the WT-CFTR; however this model does not explore the folding process and therefore may strengthen the notion of a misfolding mutation. This study describes phenotypically patients carrying the I1234V mutation. Compared to patients homozygous for F508del, these patients present with more favorable outcome. Structural models show high similarity between the static and dynamics pictures obtained for both the mutated and the WT-CFTR; however this model does not explore the folding process and therefore may strengthen the notion of a misfolding mutation. Though the relationship between chronic rhinosinusitis (CRS) and lower airway diseases is well recognized, the impact of CRS on bronchial wall structure has not been elucidated. Here, we evaluated the bronchial wall structure of CRS patients with or without diagnosed airway diseases by three-dimensional computed tomography (3D-CT). Subjects who underwent both chest CT and sinus CT within a year were recruited from consecutive medical records. CRS was defined as a Lund-Mackay score (LMS) of over 5 points. Airway dimensions were measured using validated software. Standard blood tests and pulmonary function tests were performed, and their correlation with airway thickness was examined. One-hundred-seventy-two patients were recruited (93 CRS subjects and 79 non-CRS subjects). The bronchial walls of CRS subjects were significantly thicker than those of non-CRS subjects. CRS and asthma were related to bronchial wall thickening by multivariate linear regression analysis adjusted for age, smoking status, and chest symptoms. In addition, LMS was significantly correlated with bronchial wall thickening. Airway walls in CRS subjects were thicker than those in non-CRS subjects and associated with the severity of CRS. These data indicate strong relationship between upper and lower airways regardless of chest symptoms or diagnosed airway diseases. Airway walls in CRS subjects were thicker than those in non-CRS subjects and associated with the severity of CRS. These data indicate strong relationship between upper and lower airways regardless of chest symptoms or diagnosed airway diseases. Within asthma, the small airways (≤2mm in diameter) play an important role in pathophysiology. Using a combined clinical-computational approach, we sought to more precisely evaluate the contribution of the small airways to deep-breath induced airway dilation (in