Rhinovirus protease cleavage of nucleoporins: perspective on implications for airway remodeling.

Human Rhinoviruses (RV) are a major cause of common colds and infections in early childhood and can lead to subsequent development of asthma via an as yet unknown mechanism. Asthma is a chronic inflammatory pulmonary disease characterized by significant airway remodeling. A key component of airway remodeling is the transdifferentiation of airway epithelial and fibroblast cells into cells with a more contractile phenotype. Interestingly, transforming growth factor-beta (TGF-ß), a well characterized inducer of transdifferentiation, is significantly higher in airways of asthmatics compared to non-asthmatics. RV infection induces TGF-ß signaling, at the same time nucleoporins (Nups), including Nup153, are cleaved by RV proteases disrupting nucleocytoplasmic transport. As Nup153 regulates nuclear export of SMAD2, a key intermediate in the TGF-ß transdifferentiation pathway, its loss of function would result in nuclear retention of SMAD2 and dysregulated TGF-ß signaling. We hypothesize that RV infection leads to increased nuclear SMAD2, resulting in sustained TGF-ß induced gene expression, priming the airway for subsequent development of asthma. Our hypothesis brings together disparate studies on RV, asthma and Nup153 with the aim to prompt new research into the role of RV infection in development of asthma.

The performance of three estimates of glomerular filtration rate before and after live donor nephrectomy.

Serum creatinine-based estimates of glomerular filtration rate (GFR) are inaccurate in healthy individuals. Therefore, their use in assessment prior to live donor nephrectomy has been restricted. There are less data on their use postdonor nephrectomy. This study assessed three GFR estimates against Cr(51) EDTA radioisotope GFR (iGFR) in the same cohort of patients before and after donor nephrectomy. A total of 206 patients underwent iGFR measurement prior to donor nephrectomy and this was repeated in 187 patients 6-8 weeks postsurgery. The iGFR was compared with the modification of diet in renal disease (eGFR), Cockcroft-Gault (cgGFR) and Mayo Clinic equation (mcGFR) estimates of GFR. Preoperatively, all GFR estimates performed poorly against iGFR; however, mcGFR provided the most reliable estimate. The eGFR underestimated iGFR by 23.60 +/- 16.43 ml/min/1.73 m(2), cgGFR by 15.54 +/- 18.13 ml/min/1.73 m(2) and mcGFR overestimated by 0.72 +/- 18.11 ml/min/1.73 m(2). Postdonation, all estimates again performed poorly, but eGFR and mcGFR outperformed cgGFR. The eGFR underestimated iGFR by 9.13 +/- 10.11 ml/min/1.73 m(2), mcGFR by 9.44 +/- 13.80 ml/min/1.73 m(2) and cgGFR overestimated by 6.42 +/- 14.49 ml/min/1.73 m(2). No GFR estimate performed sufficiently well to supersede iGFR measurement prior to donor nephrectomy. Performance postdonation was little better. In addition, there was no correlation between fall in iGFR and fall in GFR estimates postdonation.