Plos One
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Gene therapy model of X-linked severe combined immunodeficiency using a modified foamy virus vector.
X-linked severe combined immunodeficiency (SCID-X1) is an inherited genetic immunodeficiency associated with mutations in the common cytokine receptor γ chain (γc) gene, and characterized by a complete defect of T and natural killer (NK) cells. Gene therapy for SCID-X1 using conventional retroviral (RV) vectors carrying the γc gene results in the successful reconstitution of T cell immunity. However, the high incidence of vector-mediated T cell leukemia, caused by vector insertion near or within cancer-related genes has been a serious problem. ⋯ To evaluate the therapeutic efficacy, bone marrow cells from γc-knockout (γc-KO) mice were infected with the FV vector and transplanted into γc-KO mice. Transplantation of the FV-treated cells resulted in the successful reconstitution of functionally active T and B cells. These data suggest that FV vectors can be effective and may be safer than conventional RV vectors for gene therapy for SCID-X1.
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Lipid rafts are subdomains of the cell membrane with distinct protein composition and high concentrations of cholesterol and glycosphingolipids. Raft proteins are thought to mediate diverse cellular processes including signal transduction. However, its cellular mechanisms remain unclear. ⋯ Last, Flot-2 interacted with cav-1 and limited its expression. Taken together, we found that Flot-2 protected cells from Fas induced apoptosis and counterbalanced the pro-apoptotic effects of cav-1. Thus, Flot-2 played crucial functions in cellular homeostasis and cell survival, suggesting a differential role of individual raft proteins.
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It has been suggested that delayed intensive care unit (ICU) transfer is associated with increased mortality for patients with community-acquired pneumonia (CAP). However, ICU admission policies and patient epidemiology vary widely across the world depending on local hospital practices and organizational constraints. We hypothesized that the time from the onset of CAP symptoms to invasive mechanical ventilation could be a relevant prognostic factor. ⋯ This study suggested that the duration or delay in the time to intubation from the onset of CAP symptoms was associated with the outcomes in those patients who ultimately required invasive mechanical ventilation.
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Changes in kidney function, as assessed by early and even small variations in serum creatinine (ΔsCr), affect survival in adults following cardiac surgery but such associations have not been reported in infants. This raises the question of the adequate assessment of kidney function by early ΔsCr in infants undergoing cardiac surgery. ⋯ The present results suggest that a postoperative decrease in creatinine represents the normal course in neonates and infants with cardiac surgery, and that early creatinine variations lack sensitivity for the assessment of the severity of kidney injury.
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Semaphorin 3A is a new early diagnostic biomarker of experimental and pediatric acute kidney injury.
Semaphorin 3A is a secreted protein that regulates cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. However, nothing is known about its role in kidney pathophysiology. Here, we determined whether semaphorin3A is induced after acute kidney injury (AKI) and whether urinary semaphorin 3A can predict AKI in humans undergoing cardiopulmonary bypass (CPB). ⋯ Our results suggest that semaphorin 3A is an early, predictive biomarker in experimental and pediatric AKI, and may allow for the reliable early diagnosis and prognosis of AKI after CPB, much before the rise in serum creatinine.