Glucocorticoids: mechanisms of action and anti-inflammatory potential in asthma.

GLUCOCORTICOIDS are potent inhibitors of inflammatory processes and are widely used in the treatment of asthma. The anti-inflammatory effects are mediated either by direct binding of the glucocorticoid/glucocorticoid receptor complex to glucocorticoid responsive elements in the promoter region of genes, or by an interaction of this complex with other transcription factors, in particular activating protein-1 or nuclear factor-kappaB. Glucocorticoids inhibit many inflammation-associated molecules such as cytokines, chemokines, arachidonic acid metabolites, and adhesion molecules. In contrast, anti-inflammatory mediators often are up-regulated by glucocorticoids. In vivo studies have shown that treatment of asthmatic patients with inhaled glucocorticoids inhibits the bronchial inflammation and simultaneously improves their lung function. In this review, our current knowledge of the mechanism of action of glucocorticoids and their anti-inflammatory potential in asthma is described. Since bronchial epithelial cells may be important targets for glucocorticoid therapy in asthma, the effects of glucocorticoids on epithelial expressed inflammatory genes will be emphasized

Kinetic simulation of an extreme ultraviolet radiation driven plasma near a multilayer mirror

Future generation lithog. tools will use extreme UV radiation to enable the printing of sub-50 nm features on silicon wafers. The extreme UV radiation, coming from a pulsed discharge, photoionizes the low pressure background gas in the tool. A weakly ionized plasma is formed, which will be in contact with the optical components of the lithog. device. In the plasma sheath region ions will be accelerated towards the surfaces of multilayer mirrors. A self-consistent kinetic particle-in-cell model has been applied to describe a radiation driven plasma. The simulations predict the plasma parameters and notably the energy at which ions impact on the plasma boundaries. We have studied the influence of photoelectron emission from the mirror on the sheath dynamics and on the ion impact energy. Furthermore, the ion impact energy distribution has been convoluted with the formula of Yamamura and Tawara [At. Data Nucl. Data Tables 62, 149 (1996)] for the sputter yield to obtain the rate of phys. sputtering. The model predicts that the sputter rate is dominated by the presence of doubly ionized argon ions. [on SciFinder (R)

Next-generation antigen receptor sequencing of paired diagnosis and relapse samples of B-cell acute lymphoblastic leukemia: Clonal evolution and implications for minimal residual disease target selection

Antigen receptor gene rearrangements are frequently applied as molecular targets for detection of minimal residual disease (MRD) in B-cell precursor acute lymphoblastic leukemia patients. Since such targets may be lost at relapse, appropriate selection of antigen receptor genes as MRD-PCR target is critical. Recently, next-generation sequencing (NGS) – much more sensitive and quantitative than classical PCR-heteroduplex approaches – has been introduced for identification of MRD-PCR targets. We evaluated 42 paired diagnosis-relapse samples by NGS (IGH, IGK, TRG, TRD, and TRB) to evaluate clonal evolution patterns and to design an algorithm for selection of antigen receptor gene rearrangements most likely to remain stable at relapse. Overall, only 393 out of 1446 (27%) clonal rearrangements were stable between diagnosis and relapse. If only index clones with a frequency >5% at diagnosis were taken into account, this number increased to 65%; including only index clones with an absolute read count >10,000, indicating truly major clones, further increased the stability to 84%. Over 90% of index clones at relapse were also present as index clone at diagnosis. Our data provide detailed information about the stability of antigen receptor gene rearrangements, based on which we propose an algorithm for selecting stable MRD-PCR targets, successful in >97% of patients