The intratracheal administration of endotoxin: X. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo

Intratracheal instillation of endotoxin (LPS) causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the airspace, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-l α , MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44515/1/10753_2005_Article_BF01487403.pd

On the Antenna Beam Shape Reconstruction Using Planet Transit

The calibration of the in-flight antenna beam shape and possible beamdegradation is one of the most crucial tasks for the upcoming Planck mission. We examine several effects which could significantly influence the in-flight main beam calibration using planet transit: the problems of the variability of the Jupiter's flux, the antenna temperature and passing of the planets through the main beam. We estimate these effects on the antenna beam shape calibration and calculate the limits on the main beam and far sidelobe measurements, using observations of Jupiter and Saturn. We also discuss possible effects of degradation of the mirror surfaces and specify corresponding parameters which can help us to determine these effects.Comment: 10 pages, 8 figure

Broadband Meter-Wavelength Observations of Ionospheric Scintillation

Intensity scintillations of cosmic radio sources are used to study astrophysical plasmas like the ionosphere, the solar wind, and the interstellar medium. Normally these observations are relatively narrow band. With Low Frequency Array (LOFAR) technology at the Kilpisj\"arvi Atmospheric Imaging Receiver Array (KAIRA) station in northern Finland we have observed scintillations over a 3 octave bandwidth. ``Parabolic arcs'', which were discovered in interstellar scintillations of pulsars, can provide precise estimates of the distance and velocity of the scattering plasma. Here we report the first observations of such arcs in the ionosphere and the first broad-band observations of arcs anywhere, raising hopes that study of the phenomenon may similarly improve the analysis of ionospheric scintillations. These observations were made of the strong natural radio source Cygnus-A and covered the entire 30-250\,MHz band of KAIRA. Well-defined parabolic arcs were seen early in the observations, before transit, and disappeared after transit although scintillations continued to be obvious during the entire observation. We show that this can be attributed to the structure of Cygnus-A. Initial results from modeling these scintillation arcs are consistent with simultaneous ionospheric soundings taken with other instruments, and indicate that scattering is most likely to be associated more with the topside ionosphere than the F-region peak altitude. Further modeling and possible extension to interferometric observations, using international LOFAR stations, are discussed.Comment: 11 pages, 17 figure

Radio source calibration for the VSA and other CMB instruments at around 30 GHz

Accurate calibration of data is essential for the current generation of CMB experiments. Using data from the Very Small Array (VSA), we describe procedures which will lead to an accuracy of 1 percent or better for experiments such as the VSA and CBI. Particular attention is paid to the stability of the receiver systems, the quality of the site and frequent observations of reference sources. At 30 GHz the careful correction for atmospheric emission and absorption is shown to be essential for achieving 1 percent precision. The sources for which a 1 percent relative flux density calibration was achieved included Cas A, Cyg A, Tau A and NGC7027 and the planets Venus, Jupiter and Saturn. A flux density, or brightness temperature in the case of the planets, was derived at 33 GHz relative to Jupiter which was adopted as the fundamental calibrator. A spectral index at ~30 GHz is given for each. Cas A,Tau A, NGC7027 and Venus were examined for variability. Cas A was found to be decreasing at $0.394 \pm 0.019$ percent per year over the period March 2001 to August 2004. In the same period Tau A was decreasing at $0.22\pm 0.07$ percent per year. A survey of the published data showed that the planetary nebula NGC7027 decreased at $0.16\pm 0.04$ percent per year over the period 1967 to 2003. Venus showed an insignificant ($1.5 \pm 1.3$ percent) variation with Venusian illumination. The integrated polarization of Tau A at 33 GHz was found to be $7.8\pm 0.6$ percent at pa $= 148^\circ \pm 3^\circ$.}Comment: 13 pages, 15 figures, submitted to MNRA

Intratracheal administration of endotoxin and cytokines: VIII. LPS induces E-selectin expression; anti-E-selectin and soluble E-selectin inhibit acute inflammation

E-selectin is an inducible endothelial adhesion molecule that binds neutrophils. E-selectin mRNA is not constitutively detectable in the lungs of rats. Intratracheal injection of LPS induces pulmonary E-selectin mRNA expression at 2–4 h. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of mouse F(ab′) 2 or F(ab′)) anti-E-selectin monoclonal antibody inhibits the emigration of neutrophils into the bronchoalveolar space at 6 h by 50–70%. TNF and IL-6 bioactivity are not decreased in bronchoalveolar lavage fluid after treatment with anti-E-selectin antibody as compared to controls, suggesting that the anti-E-selectin does not affect the magnitude of the LPS-initiated cytokine cascade. Intratracheal injection of LPS followed at 2 and 4 h by intravenous injection of soluble E-selectin inhibits neutrophilic emigration at 6 h by 64%, suggesting that endogenous soluble E-selectin shed from activated endothelium may play a role in the endogenous down-regulation of acute inflammation. E-selectin-mediated adhesion of neutrophils to endothelium appears crucial to the full development of the acute inflammation response.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44513/1/10753_2005_Article_BF01534436.pd

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Morphology and kinematics of Lynds 1642

The high latitude translucent molecular cloud L1642 has been mapped in the J=1-0 and J=2-1 transitions of 12CO, 13CO and C18O using the SEST radio telescope. We have analysed the morphology and velocity structure of the cloud using the Positive Matrix Factorization (PMF) method. The results show that L1642 is composed of a main structure at radial velocity 0.2 km/s while the higher velocity components at ~0.5 and 1.0 km/s form an incomplete ring around it, suggesting an expanding shell structure. Fainter emission extends to the north with a still higher velocity of up to 1.6 km/s. Such a velocity structure suggests an elongated morphology in the line of sight direction. The physical properties of the cloud have been investigated assuming LTE conditions, but non-LTE radiative transfer models are also constructed for the 13CO observations. We confirm that L1642 follows an r^-1 density distribution in its outer parts while the distribution is considerably flatter in the core. The cloud is close to virial equilibrium. In an Appendix the PMF results are compared with the view obtained through the analysis of channel maps and by the use of Principal Component Analysis (PCA). Both PMF and PCA present the observations as a linear combination of basic spectral shapes that are extracted from the data. Comparison of the methods shows that the PMF method in particular is able to produce a presentation of the complex velocity that is both compact and easily interpreted.Comment: Accepted to A&