Effect of exogenous surfactants on viability and DNA synthesis in A549, immortalized mouse type II and isolated rat alveolar type II cells

<p>Abstract</p> <p>Background</p> <p>In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair.</p> <p>Objective</p> <p>The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis.</p> <p>Methods</p> <p>Curosurf^®and Alveofact^®were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation.</p> <p>Results</p> <p>Curosurf^®resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact^®exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models.</p> <p>Conclusion</p> <p>This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.</p

CD3Z Genetic Polymorphism in Immune Response to Hepatitis B Vaccination in Two Independent Chinese Populations

Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, vaccine-induced immunity to hepatitis B varies among individuals. CD4+ T helper cells, which play an important role in both cellular and humoral immunity, are involved in the immune response elicited by vaccination. Polymorphisms in the genes involved in stimulating the activation and proliferation of CD4+ T helper cells may influence the immune response to hepatitis B vaccination. In the first stage of the present study, a total of 111 single nucleotide polymorphisms (SNPs) in 17 genes were analyzed, using the iPLEX MassARRAY system, among 214 high responders and 107 low responders to hepatitis B vaccination. Three SNPs (rs12133337 and rs10918706 in CD3Z, rs10912564 in OX40L) were associated significantly with the immune response to hepatitis B vaccination (P = 0.008, 0.041, and 0.019, respectively). The three SNPs were analyzed further with the TaqMan-MGB or TaqMan-BHQ probe-based real-time polymerase chain reaction in another independent population, which included 1090 high responders and 636 low responders. The minor allele ‘C’ of rs12133337 continued to show an association with a lower response to hepatitis B vaccination (P = 0.033, odds radio = 1.28, 95% confidence interval = 1.01–1.61). Furthermore, in the stratified analysis for both the first and second populations, the association of the minor allele ‘C’ of rs12133337 with a lower response to hepatitis B vaccination was more prominent after individuals who were overweight or obese (body mass index ≥25 kg/m2) were excluded (1st stage: P = 0.003, 2nd stage: P = 0.002, P-combined = 9.47e-5). These findings suggest that the rs12133337 polymorphism in the CD3Z gene might affect the immune response to hepatitis B vaccination, and that a lower BMI might increase the contribution of the polymorphism to immunity to hepatitis B vaccination

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Crystal structure of a SLC11 (NRAMP) transporter reveals the basis for transition-metal ion transport

Members of the SLC11 (NRAMP) family transport iron and other transition-metal ions across cellular membranes. These membrane proteins are present in all kingdoms of life with a high degree of sequence conservation. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of Staphylococcus capitis DMT (ScaDMT), a close prokaryotic homolog of the family. ScaDMT shows a familiar architecture that was previously identified in the amino acid permease LeuT. The protein adopts an inward-facing conformation with a substrate-binding site located in the center of the transporter. This site is composed of conserved residues, which coordinate Mn(2+), Fe(2+) and Cd(2+) but not Ca(2+). Mutations of interacting residues affect ion binding and transport in both ScaDMT and human DMT1. Our study thus reveals a conserved mechanism for transition-metal ion selectivity within the SLC11 family