Rare-earth doped chalcogenide glass fibre laser

We report on the first laser action in a rare-earth doped chalcogenide glass fibre. Laser action at 1080nm was obtained in a 22mm long gallium lanthanum sulphide glass fibre with a neodymium doped core, fabricated by the rod-in-tube technique. The laser was pumped continuous wave with a Ti:sapphire laser at 815nm and showed a self-pulsing behaviour

Comparison of the roles of mitogen-activated protein kinase kinase and phosphatidylinositol 3-kinase signal transduction in neutrophil effector function

Although it is known that many stimuli can activate mitogen- activated protein kinases (MAPKs) and phosphatidylinositol 3- kinases (PI3K) in human neutrophils, little is known concerning either the mechanisms or function of this activation. We have utilized a selective inhibitor of MAPKkinase (MEK), PD098059, and two inhibitors of PI3K, wortmannin and LY294002, to investigate the roles of these kinases in the regulation of neutrophil effector functions. Granulocyte/macrophage colony- stimulating factor, platelet-activating factor (PAF) and N-for- mylmethionyl-leucyl-phenylalanine are capable of activating both p44^(ERK1) and p42^(ERK2) MAPKs and phosphotyrosine-asso- ciated PI3K in human neutrophils. The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21^(ras) by both tyrosine kinase and G-protein- coupled receptors as measured by a novel assay for GTP loading. Wortmannin and LY294002 inhibit, to various degrees, super- oxide generation, neutrophil migration and PAF release. In- cubation with PD098059, however, inhibits only the PAF release stimulated by serum-treated zymosan. This demonstrates that, while neither MEK nor ERK kinases are involved in the acti- vation of respiratory burst or neutrophil migration, inhibition of PAF release suggests a potential role in the activation of cytosolic phospholipase A2 . PI3K isoforms, however, seem to have a much wider role in regulating neutrophil functioning

Tyrosine phosphorylation-dependent activation of phosphatidylinositide 3-kinase occurs upstream of Ca^(2+)-signalling induced by Fcy receptor cross-linking in human neutrophils

The effect of wortmannin on IgG-receptor (FcyR)-mediated stimulation of human neutrophils was investigated. The Ca^(2+) influx induced by clustering of both Fcy receptors was inhibited by wortmannin, as was the release of Ca^(2+) from intracellular stores. Wortmannin also inhibited, with the same efficacy, the accumulation of Ins(1,4,5)P3 observed after FcyR stimulation, but did not affect the increase in Ins(1,4,5)P3 induced by the chemotactic peptide, formyl-methionine-leucine-phenylalanine. Because wortmannin is, in the concentrations used here, an inhibitor of PtdIns 3-kinase, these results suggested a role for PtdIns 3-kinase upstream of Ca^(2+) signalling, induced by FcyR cross-linking. Support for this notion was obtained by investigating the effect of another inhibitor of PtdIns 3-kinase, LY 294002, and by studying the kinetics of PtdIns 3-kinase activation. We found translocation of PtdIns 3-kinase to the plasma membrane and increased PtdIns 3-kinase activity in the membrane as soon as 5 s after FccR cross-linking, even before the onset of the Ca^(2+) response. Moreover, the translocation of PtdIns 3-kinase to the plasma membrane was inhibited by cocross- linking of either FcyRIIa and FcyRIIIb with the tyrosine phosphatase, CD45, indicating a requirement for protein tyrosine phosphorylation in the recruitment of PtdIns 3-kinase to the plasma membrane. Taken together, our results suggest a role for PtdIns 3-kinase in early signal transduction events after FcyR cross-linking in human neutrophils

SPECTRA OF YOUNG GALAXIES

Invited review, Ringberg conference on "Galaxies in the Young Universe" (Sept94)Comment: 12 pages, uuencoded compressed Postscript fil

Neodymium doped chalcogenide glass fibre laser

We report on laser action in a Neodymium doped Gallium Lanthanum Sulphide glass fibre. Laser action at 1080nm was obtained in a 22mm long multimode glass fibre with a neodymium doped core, fabricated by the rod-in-tube technique. The laser was pumped continuous wave with a Ti:sapphire laser at 815nm and showed a self-pulsing behaviour

Steroids induce a disequilibrium of secreted interleukin-1 receptor antagonist and interleukin-1beta synthesis by human neutrophils

Item does not contain fulltextChronic obstructive pulmonary disease (COPD) is characterised by neutrophilic inflammation in the airways and these neutrophils contribute to the production of inflammatory mediators. Dampening the production of proinflammatory mediators might be an important strategy to treat COPD and glucocorticosteroids are known to do so via inhibition of nuclear factor-kappaB. However, this pathway is important for the control of pro- and anti-inflammatory genes. We studied the effects of dexamethasone on production and secretion of pro-inflammatory interleukin (IL)-1beta and anti-inflammatory secreted IL-1 receptor antagonist (sIL-1Ra) by human neutrophils activated with tumor necrosis factor (TNF)-alpha. In vitro, TNF-alpha-stimulated neutrophils produced significant amounts of IL-1beta and sIL-1Ra; this production was inhibited by dexamethasone. However, synthesis and secretion of sIL-1Ra was inhibited at lower concentrations dexamethasone compared to IL-1beta, which changed the IL-1beta:sIL-1Ra ratio significantly. This altered ratio resulted in a more pro-inflammatory condition, as visualised by increased intercellular adhesion molecule-1 expression on human endothelial cells. In vivo, moderate-to-severe COPD patients using inhaled glucocorticosteroids have decreased plasma sIL-Ra levels compared with mild-to-moderate patients not on glucocorticosteroid treatment. In conclusion, dexamethasone induces a pro-inflammatory shift in the IL-1beta:sIL-1Ra cytokine balance in neutrophils in vitro, which might contribute to a lack of endogenous anti-inflammatory signals to dampen inflammation in vivo

Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2-Derived Cytokines Interleukin-4 and Interleukin-5

Activation and recruitment of eosinophils in allergic inflammation is in part mediated by chemoattractants and T-helper 2 (Th2)-derived cytokines. However, little is known concerning the signal transduction mechanisms by which this activation occurs. We have investigated tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase (PI3K) and compared this with the activation of the p21ras-ERK signaling pathway in human eosinophils. The related cytokines interleukin- 3 (IL-3), IL-5, and granulocyte-macrophage colonystimulating factor (GM-CSF), all induced PI3K activity detected in antiphosphotyrosine immunoprecipitates. Furthermore, the chemoattractants platelet-activating factor (PAF), RANTES, and C5a were also able to induce phosphotyrosine- associated PI3K activity. Protein kinase B (PKB) is a downstream target of PI3K activation by growth factors. Induction of PKB phosphorylation in human eosinophils was transiently induced on activation with the cytokines IL-4 and IL-5, as well as the chemoattractants PAF, C5a, and RANTES showing a broad activation profile. Surprisingly, analysis of the activation of the mitogen-activated protein (MAP) kinases p44ERK1 and p42ERK2, showed that ERK2, but not ERK1, was transiently activated in human eosinophils after stimulation with IL-5 or PAF. Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Finally, using specific inhibitors of both the p21ras-ERK and PI3K signaling pathways, a role was demonstrated for PI3K, but not p21ras-ERK, in activation of the serum-treated zymosan (STZ)-mediated respiratory burst in IL-5 and PAF-primed eosinophils. In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions

Gallium lanthanum sulphide optical fibre for active and passive applications

Gallium lanthanum sulphide glass has now been demonstrated in the form of multimode and singlemode fibre. Applications of this glass, when doped with rare earth ions, include a 1.3 micron optical fibre amplifier and long wavelength sources operating in the 3-5 micron region. For these applications to be practical, effort is required to decrease fibre loss. This paper deals with progress to date in the achievement of a low loss gallium lanthanum sulphide fibre. Loss due to absorption by impurities is identified and sources of scattering indicated. Efforts to minimize these extrinsic loss sources are described. The properties of the best fibre achieved to date are described and emerging applications outlined