A 1.5-year-old male Arabian horse was referred to the Louisiana State University Veterinary Teaching Hospital and Clinic for an open deep laceration involving two thirds of the right trunk. The initial CBC results included an inflammatory leukogram, characterized by a marked degenerative left shift consisting of only immature band neutrophils (7500/microL, reference interval 0-100/microL) with toxic changes and no segmented neutrophils (0/microL, reference interval 2700-6700/microL). On abdominal ultrasonography, free abdominal fluid was found and collected for analysis. Abdominal fluid had a marked increase in total nucleated cells (40,600 cells/microL) consisting of 74% nondegenerate neutrophils that all were hyposegmented, with mature condensed chromatin. Re-evaluation of neutrophil morphology on the initial blood smear confirmed hyposegmentation and mature condensed chromatin, similar to that observed in cells in the abdominal fluid. A diagnosis of Pelger-Huët anomaly (PHA) was made in this colt. Congenital PHA was documented on the basis of persistent neutrophil hyposegmentation on serial blood smears, ruling out of acquired causes of PHA, and findings of similar neutrophil hyposegmentation on blood smears from the colt's sire and the sire's siblings. To our knowledge, this is the first reported case of congenital PHA in a horse.
In cystic fibrosis (CF) respiratory failure caused by progressive airway obstruction and tissue damage is primarily a result of the aberrant inflammatory responses to lung infections with Pseudomonas aeruginosa. Despite considerable improvement in patient survival, conventional therapies are mainly supportive. Recent progress towards gene therapy for CF has been encouraging; however, several factors such as immune response and transduced cell turnover remain as potential limitations to CF gene therapy. As alternative gene therapy vectors for CF we examined the feasibility of using SV40-derived vectors (rSV40s) which may circumvent some of these obstacles. To accommodate the large CFTR cDNA, we removed not only SV40 Tag genes, but also all capsid genes. We therefore tested whether “gutless” rSV40s could be packaged and were able to express a functional human CFTR cDNA. Results from our in vitro analysis determined that rSV40-CFTR was able to successfully result in the expression of CFTR protein which localized to the plasma membrane and restored channel function to CFTR deficient cells. Similarly in vivo experiments delivering rSV40-CFTR to the lungs of Cftr−/− mice resulted in a reduction of the pathology associated with intra-tracheal pseudomona aeruginosa challenge. rSV40-CFTR treated mice had had less weight loss when compared to control treated mice as well as demonstrably reduced lung inflammation as evidence by histology and reduced inflammatory cytokines in the BAL. The reduction in inflammatory cytokine levels led to an evident decrease in neutrophil influx to the airways. These results indicate that further study of the application of rSV40-CFTR to CF gene therapy is warranted.
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