Comparative studies on short‐chain and long‐chain crosslinking in polyurethane networks

Isocyanate terminated prepolymers were synthesised using poly(tetramethylene oxide) glycol of molecular weight 1 000 (PTMG₁₀₀₀) and poly(propylene oxide) glycol of molecular weight 1 000 (PPG₁₀₀₀) with tolylene‐2,4‐diisocyanate (TDI). The prepolymers were chain extended with N,N‐bis(2‐hydroxyethyl)isonicotinamide to form polyurethanes containing pyridine moieties. These polyurethanes were converted to cationomers by crosslinking with (a) 1,4‐dibromobutane to form short‐chain crosslinked polymers (SCCPs) and (b) bromine‐terminated prepolymers to form long‐chain crosslinked polymers (LCCPs). The cationomers were characterised by Fourier transform infrared spectroscopy, thermal and mechanical analysis. FTIR spectral results of SCCPs and LCCPs confirmed the quaternisation of heterocyclic nitrogen leading to crosslinking. Dynamic mechanical analysis showed better damping properties for LCCPs than SCCPs. The stress‐strain measurements showed higher elongation and lower tensile strength for LCCPs.     

Urothelial carcinoma arising from the transplanted kidney: A single‐center experience and literature review

Urothelial carcinoma (UC) is a malignancy predominantly arising in the bladder. Upper tract UC (UUC) is uncommon, accounting only for 5‐10% of the cases. High incidence of neoplasms is associated with immunosuppressive therapy; thus, UCs of the transplanted grafts often lead to a more aggressive treatment, in order to withdraw completely the immunosuppression. It significantly affects the patient quality of life, meaning return to dialysis, along with the worse life expectancy. We present our single‐institution experience of this rare malignancy in two mid‐age kidney transplant recipients, with UCs successfully treated with radical nephroureterectomy: G3 pT3 N0 + G3 pT1 N0 in the first patient and G3 pT2 N0 in the second one. We also review the previous literature focusing on stage of presentation and treatment for the affected kidney transplant patients.     

Ex vivo perfusion induces a time‐ and perfusate‐dependent molecular repair response in explanted porcine lungs

Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty‐nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI‐related genes was measured and correlated with function and histology. Twenty‐eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28‐gene set expression peaked after 6 hours of EVLP, whereas downregulated 6‐gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6‐gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.     

Neutrophil elastase, an innate immunity effector molecule, represses flagellin transcription in Pseudomonas aeruginosa

Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors triggers an innate immune response to colonizing or invading bacteria. Conversely, many bacteria have evolved mechanisms to dampen this response by downregulating the synthesis of such PAMPs. We have previously demonstrated that Pseudomonas aeruginosa growing in mucopurulent human respiratory mucus from cystic fibrosis patients represses the expression of its flagellin, a potent stimulant of the innate immune response. Here we demonstrate that this phenomenon occurs in response to the presence of neutrophil elastase in such mucus. Nonpurulent mucus from animals had no such repressive effect. Furthermore, lysed neutrophils from human blood reproduced the flagellin-repressive effect ex mucus and, significantly, had no effect on the viability of this organism. Neutrophil elastase, a component of the innate host defense system, has been described to be bactericidal for gram-negative bacteria and to degrade bacterial virulence factors. Thus, the resistance of P. aeruginosa to the bactericidal effect of neutrophil elastase, as well as this organism's ability to sense this enzyme's presence and downregulate the synthesis of a PAMP, may be the key factors in allowing P. aeruginosa to colonize the lungs. These findings demonstrate the dynamic nature of this bacterium's response to host defenses that ensures its success as a colonizer and also highlights the dual nature of defense molecules that confer advantages and disadvantages to both hosts and pathogens.     

Production and characterization of guinea pig recombinant gamma interferon and its effect on macrophage activation

Gamma interferon (IFN-gamma) plays a critical role in the protective immune responses against mycobacteria. We previously cloned a cDNA coding for guinea pig IFN-gamma (gpIFN-gamma) and reported that BCG vaccination induced a significant increase in the IFN-gamma mRNA expression in guinea pig cells in response to living mycobacteria and that the virulent H37Rv strain of Mycobacterium tuberculosis stimulated less IFN-gamma mRNA than did the attenuated H37Ra strain. In this study, we successfully expressed and characterized recombinant gpIFN-gamma with a histidine tag at the N terminus (His-tagged rgpIFN-gamma) in Escherichia coli. rgpIFN-gamma was identified as an 18-kDa band in the insoluble fraction; therefore, the protein was purified under denaturing conditions and renatured. N-terminal amino acid sequencing of the recombinant protein yielded the sequence corresponding to the N terminus of His-tagged gpIFN-gamma. The recombinant protein upregulated major histocompatibility complex class II expression in peritoneal macrophages. The antiviral activity of rgpIFN-gamma was demonstrated with a guinea pig fibroblast cell line (104C1) infected with encephalomyocarditis virus. Interestingly, peritoneal macrophages treated with rgpIFN-gamma did not produce any nitric oxide but did produce hydrogen peroxide and suppressed the intracellular growth of mycobacteria. Furthermore, rgpIFN-gamma induced morphological alterations in cultured macrophages. Thus, biologically active rgpIFN-gamma has been successfully produced and characterized in our laboratory. The study of rgpIFN-gamma will further increase our understanding of the cellular and molecular responses induced by BCG vaccination in the guinea pig model of pulmonary tuberculosis.     

Antrochoanal Polyp Presenting as Obstructive Sleep Apnea

Antrochoanal polyps (ACPS) are uncommon in children presenting to the pediatric clinic. They commonly present with unilateral nasal obstruction. ACPS presenting as obstructive sleep apnea (OSA) in a young child is an uncommon initial presentation. A high level of suspicion is needed to diagnose OSA in young children as the presenting symptoms may be nonspecific and sometimes misleading.