Cross-Desensitization of Chemoattractant Receptors Occurs at Multiple Levels: Evidence for a Role for Inhibition of Phospholipase C Activity

To define the molecular mechanisms of cross-regulation among chemoattractant receptors, we stably coexpressed, in a rat basophilic leukemia (RBL-2H3) cell line, epitope-tagged receptors for the chemoattractants formylmethionylleucylphenylalanine (fMLP), a peptide of the fifth component of the complement system (C5a), and interleukin-8 (IL-8). All the expressed receptors underwent homologous phosphorylation and desensitization upon agonist stimulation. When co-expressed, epitope-tagged C5a receptor (ET-C5aR) and epitope-tagged IL-8 receptor (ET-IL-8RA) were cross-phosphorylated by activation of the other. Activation of epitope- tagged fMLP receptor (ET-FR) also cross-phosphorylated ET-C5aR and ET-IL- 8RA, but ET-FR was totally resistant to cross-phosphorylation. Similarly, C5a and IL-8 stimulation of [35S]guanosine 5\u27-3-P-(thio) triphosphate (GTPγS) binding and Ca2+ mobilization were cross-desensitized by each other and by fMLP. Stimulation of [35S]GTPγS binding by fMLP was also not cross- desensitized by C5a or IL-8, however, Ca2+ mobilization was, suggesting a site of inhibition distal to G protein activation. Consistent with this desensitization of Ca2+ mobilization, inositol 1,4,5-trisphosphate release in RBL-2H3 cells expressing both ET-C5aR and ET-FR revealed that fMLP and C5a cross-desensitized each other\u27s ability to stimulate phosphoinositide hydrolysis. Taken together, these results indicate that receptor cross- phosphorylation correlates directly with desensitization at the level of G protein activation. The ET-FR was resistant to this process. Of note, cross- desensitization of ET-FR at the level of phosphoinositide hydrolysis and Ca2+ mobilization was demonstrated in the absence of receptor phosphorylation. This suggests a new form of chemoattractant cross-regulation at a site distal to receptor/G protein coupling, involving the activity of phospholipase C

Evaluation of the self-energy correction to the g-factor of S states in H-like ions

A detailed description of the numerical procedure is presented for the evaluation of the one-loop self-energy correction to the $g$-factor of an electron in the $1s$ and $2s$ states in H-like ions to all orders in $Z\alpha$.Comment: Final version, December 30, 200

Opiates Transdeactivate Chemokine Receptors: δ and μ Opiate Receptor- Mediated Heterologous Desensitization

An intact chemotactic response is vital for leukocyte trafficking and host defense. Opiates are known to exert a number of immunomodulating effects in vitro and in vivo, and we sought to determine whether they were capable of inhibiting chemokine-induced directional migration of human leukocytes, and if so, to ascertain the mechanism involved. The endogenous opioid met- enkephalin induced monocyte chemotaxis in a pertussis toxin-sensitive manner. Metenkephalin, as well as morphine, inhibited IL-8-induced chemotaxis of human neutrophils and macrophage inflammatory protein (MIP)-1α, regulated upon activation, normal T expressed and secreted (RANTES), and monocyte chemoattractant protein 1, but not MIP-1β-induced chemotaxis of human monocytes. This inhibition of chemotaxis was mediated by δ and μ but not κ G protein-coupled opiate receptors. Calcium flux induced by chemokines was unaffected by met-enkephalin pretreatment. Unlike other opiate-induced changes in leukocyte function, the inhibition of chemotaxis was not mediated by nitric oxide. Opiates induced phosphorylation of the chemokine receptors CXCR1 and CXCR2, but neither induced internalization of chemokine receptors nor perturbed chemokine binding. Thus, inhibition of chemokine-induced chemotaxis by opiates is due to heterologous desensitization through phosphorylation of chemokine receptors. This may contribute to the defects in host defense seen with opiate abuse and has important implications for immunomodulation induced by several endogenous neuropeptides which act through G protein-coupled receptors

Loop-after-loop contribution to the second-order Lamb shift in hydrogenlike low-Z atoms

We present a numerical evaluation of the loop-after-loop contribution to the second-order self-energy for the ground state of hydrogenlike atoms with low nuclear charge numbers Z. The calculation is carried out in the Fried-Yennie gauge and without an expansion in Z \alpha. Our calculation confirms the results of Mallampalli and Sapirstein and disagrees with the calculation by Goidenko and coworkers. A discrepancy between different calculations is investigated. An accurate fitting of the numerical results provides a detailed comparison with analytic calculations based on an expansion in the parameter Z \alpha. We confirm the analytic results of order \alpha^2 (Z\alpha)^5 but disagree with Karshenboim's calculation of the \alpha^2 (Z \alpha)^6 \ln^3(Z \alpha)^{-2} contribution.Comment: RevTex, 19 pages, 4 figure

Phase Structure and Nonperturbative States in Three-Dimensional Adjoint Higgs Model

The thermodynamics of 3d adjoint Higgs model is considered. We study the properties of the Polyakov loop correlators and the critical behavior at the deconfinement phase transition. Our main tool is a reduction to the 2d sine-Gordon model. The Polyakov loops appear to be connected with the soliton operators in it. The known exact results in the sine-Gordon theory allow us to study in detail the temperature dependence of the string tension, as well as to get some information about a nonperturbative dynamics in the confinement phase. We also consider the symmetry restoration at high temperature which makes it possible to construct the phase diagram of the model completely.Comment: 15pp., Revtex; 4 figures; replaced by a version to be published in Phys. Rev.

Nondestructive Neutron And Gamma-Ray Technologies Applied To GNEP And Safeguards

In recent years, LLNL has developed methods for diagnosing significant quantities of special nuclear material (SNM). Homeland security problems have recently focused our attention on detection of shielded highly enriched uranium (HEU), which is a weak signal problem. Current and advanced safeguards applications will require working in the opposite extreme of strong but buried signals. We will review some of the technologies that have been developed at LLNL for homeland security applications and discuss how they might be used in support of international safeguards

[89Zr]Oxinate4 for long-term in vivo cell tracking by positron emission tomography

Purpose 111In (typically as [111In]oxinate3) is a gold standard radiolabel for cell tracking in humans by scintigraphy. A long half-life positron-emitting radiolabel to serve the same purpose using positron emission tomography (PET) has long been sought. We aimed to develop an 89Zr PET tracer for cell labelling and compare it with [111In]oxinate3 single photon emission computed tomography (SPECT). Methods [89Zr]Oxinate4 was synthesised and its uptake and efflux were measured in vitro in three cell lines and in human leukocytes. The in vivo biodistribution of eGFP-5T33 murine myeloma cells labelled using [89Zr]oxinate4 or [111In]oxinate3 was monitored for up to 14 days. 89Zr retention by living radiolabelled eGFP-positive cells in vivo was monitored by FACS sorting of liver, spleen and bone marrow cells followed by gamma counting. Results Zr labelling was effective in all cell types with yields comparable with 111In labelling. Retention of 89Zr in cells in vitro after 24 h was significantly better (range 71 to >90 %) than 111In (43–52 %). eGFP-5T33 cells in vivo showed the same early biodistribution whether labelled with 111In or 89Zr (initial pulmonary accumulation followed by migration to liver, spleen and bone marrow), but later translocation of radioactivity to kidneys was much greater for 111In. In liver, spleen and bone marrow at least 92 % of 89Zr remained associated with eGFP-positive cells after 7 days in vivo. Conclusion [89Zr]Oxinate4 offers a potential solution to the emerging need for a long half-life PET tracer for cell tracking in vivo and deserves further evaluation of its effects on survival and behaviour of different cell types

Multibaryons as Symmetric Multiskyrmions

We study non-adiabatic corrections to multibaryon systems within the bound state approach to the SU(3) Skyrme model. We use approximate ansatze for the static background fields based on rational maps which have the same symmetries of the exact solutions. To determine the explicit form of the collective Hamiltonians and wave functions we only make use of these symmetries. Thus, the expressions obtained are also valid in the exact case. On the other hand, the inertia parameters and hyperfine splitting constants we calculate do depend on the detailed form of the ansatze and are, therefore, approximate. Using these values we compute the low lying spectra of multibaryons with B <= 9 and strangeness 0, -1 and -B. Finally, we show that the non-adiabatic corrections do not affect the stability of the tetralambda and heptalambda found in a previous work.Comment: 17 pages, RevTeX, no figure