Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course

Demonstration of Robust Quantum Gate Tomography via Randomized Benchmarking

Typical quantum gate tomography protocols struggle with a self-consistency problem: the gate operation cannot be reconstructed without knowledge of the initial state and final measurement, but such knowledge cannot be obtained without well-characterized gates. A recently proposed technique, known as randomized benchmarking tomography (RBT), sidesteps this self-consistency problem by designing experiments to be insensitive to preparation and measurement imperfections. We implement this proposal in a superconducting qubit system, using a number of experimental improvements including implementing each of the elements of the Clifford group in single `atomic' pulses and custom control hardware to enable large overhead protocols. We show a robust reconstruction of several single-qubit quantum gates, including a unitary outside the Clifford group. We demonstrate that RBT yields physical gate reconstructions that are consistent with fidelities obtained by randomized benchmarking

Upregulation of Transglutaminase andε(γ-Glutamyl)-Lysine in the Fisher-Lewis Rat Model of Chronic Allograft Nephropathy

Background. Tissue transglutaminase (TG2), a cross-linking enzyme, modulates deposition of extracellular matrix protein in renal fibrosis. This study aimed to examine TG2 and its cross-link product ε(γ-glutamyl)-lysine in the Fisher-Lewis rat renal transplantation (RTx) model of chronic allograft nephropathy (CAN). Materials and Methods. Left renal grafts from male Fisher and Lewis were transplanted into Lewis rats, generating allografts and isografts, respectively. Blood pressure, renal function, and proteinuria were monitored for up to 52 weeks. At termination, CAN was assessed in the renal tissue by light and electron microscopy, TG2 and ε(γ-glutamyl)-lysine by immunofluorescence, and the urinary ε(γ-glutamyl)-lysine by high performance liquid chromatography. Results. Compared to the isograft, the allografts were hypertensive, proteinuric, and uraemic and developed CAN. Extracellular TG2 (glomerulus: 64.55 + 17.61 versus 2.11 + 0.17, P<0.001; interstitium: 13.72 + 1.62 versus 3.19 + 0.44, P<0.001), ε(γ-glutamyl)-lysine (glomerulus: 21.74 + 2.71 versus 1.98 + 0.37, P<0.01; interstitium: 37.96 + 17.06 versus 0.42 + 0.11, P<0.05), TG2 enzyme activity (1.09 + 0.13 versus 0.41 + 0.03 nmol/h/mg protein, P<0.05), TG2 mRNA (20-fold rise), and urinary ε(γ-glutamyl)-lysine (534.2 + 198.4 nmol/24 h versus 57.2 + 4.1 nmol/24 h,P<0.05) levels were significantly elevated in the allografts and showed a positive linear correlation with tubulointerstitial fibrosis. Conclusion. CAN was associated with upregulation of renal TG2 pathway, which has a potential for pharmacological intervention. The elevated urinary ε(γ-glutamyl)-lysine, measured for the first time in RTx, is a potential biomarker of CA

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Preliminary Results for LP VPE X-Ray Detectors

Thick epitaxial layers have been grown using Low Pressure Vapour Phase Epitaxy techniques with low free carrier concentrations . This type of material is attractive as a medium for X-ray detection, because of its high conversion efficiency for X-rays in the medically interesting energy range.Comment: 4 pages. PS file only - original in WORD. Also available at http://ppewww.ph.gla.ac.uk/preprints/97/07

Binary Collisions and the Slingshot Effect

We derive the equations for the gravity assist manoeuvre in the general 2D case without the constraints of circular planetary orbits or widely different masses as assumed by Broucke, and obtain the slingshot conditions and maximum energy gain for arbitrary mass ratios of two colliding rigid bodies. Using the geometric view developed in an earlier paper by the authors the possible trajectories are computed for both attractive or repulsive interactions yielding a further insight on the slingshot mechanics and its parametrization. The general slingshot manoeuvre for arbitrary masses is explained as a particular case of the possible outcomes of attractive or repulsive binary collisions, and the correlation between asymptotic information and orbital parameters is obtained in general.Comment: 12 pages, 7 figures, accepted for publication Dec'07, Celestial Mechanics and Dynamical Astronom