Chemokines: structure, receptors and functions. A new target for inflammation and asthma therapy?

Five to 10% of the human population have a disorder of the respiratory tract called ‘asthma’. It has been known as a potentially dangerous disease for over 2000 years, as it was already described by Hippocrates and recognized as a disease entity by Egyptian and Hebrew physicians. At the beginning of this decade, there has been a fundamental change in asthma management. The emphasis has shifted from symptom relief with bronchodilator therapies (e.g. β2-agonists) to a much earlier introduction of anti-inflammatory treatment (e.g. corticosteroids). Asthma is now recognized to be a chronic inflammatory disease of the airways, involving various inflammatory cells and their mediators. Although asthma has been the subject of many investigations, the exact role of the different inflammatory cells has not been elucidated completely. Many suggestions have been made and several cells have been implicated in the pathogenesis of asthma, such as the eosinophils, the mast cells, the basophils and the lymphocytes. To date, however, the relative importance of these cells is not completely understood. The cell type predominantly found in the asthmatic lung is the eosinophil and the recruitment of these eosinophils can be seen as a characteristic of asthma. In recent years much attention is given to the role of the newly identified chemokines in asthma pathology. Chemokines are structurally and functionally related 8–10 kDa peptides that are the products of distinct genes clustered on human chromosomes 4 and 17 and can be found at sites of inflammation. They form a superfamily of proinflammatory mediators that promote the recruitment of various kinds of leukocytes and lymphocytes. The chemokine superfamily can be divided into three subgroups based on overall sequence homology. Although the chemokines have highly conserved amino acid sequences, each of the chemokines binds to and induces the chemotaxis of particular classes of white blood cells. Certain chemokines stimulate the recruitment of multiple cell types including monocytes, lymphocytes, basophils, and eosinophils, which are important cells in asthma. Intervention in this process, by the development of chemokine antagonists, might be the key to new therapy. In this review we present an overview of recent developments in the field of chemokines and their role in inflammations as reported in literature

Cardiac amyloidosis

The frequency of cardiac involvement varies among other types of amyloidosis. Cardiac amyloidosis leads to systolic and diastolic dysfunction with symptoms of heart failure. Cardiac magnetic resonance (CMR) findings are helpful in supporting the diagnosis of amyloid cardiomyopathy. We report a case of a 73-year-old man who presented with shortness of breath. Echocardiography showed a hypertrophic, diffusely hypocontractile left ventricle with a restrictive filling pattern. The diagnosis of an isolated amyloidosis was made on CMR

Photoemission investigation of the electronic structure of Fe-Pd and Fe-Pt alloys

A photoemission investigation of Fe-Pd and Fe-Pt transition-metal alloys, using ∼50–150-eV synchrotron radiation, is presented. We consider in particular the spectral distribution of Fe states when approaching the dilute limit. By means of the Cooper minimum in the 4d and 5d photoionization cross section, we identify structures that have mainly Fe minority- or Fe majority-spin character. The relative position of these peaks is discussed in terms of the covalent interaction between Fe 3d and Pd or Pt d states. Also, the strong resemblance between the distribution of Fe states in the Pd-based and in the Pt-based alloys is demonstrated. We find a consistent behavior of interacting d states towards the dilute limit. It is concluded that the Fe states that are observed in the photoemission spectra of the dilute alloys have mainly majority-spin character and are, because of the covalent interaction with host states, widely distributed over the energy range of the host d band. The Fe minority-spin band, which is centered near the Fermi level, gradually empties with increasing Fe dilution

Sakurai's Object: characterizing the near-infrared CO ejecta between 2003 and 2007

We present observations of Sakurai's Object obtained at 1–5 μm between 2003 and 2007. By fitting a radiative transfer model to an echelle spectrum of CO fundamental absorption features around 4.7 μm, we determine the excitation conditions in the line-forming region. We find 12C/13C = 3.5+2.0−1.5, consistent with CO originating in ejecta processed by the very late thermal pulse, rather than in the pre-existing planetary nebula. We demonstrate the existence of 2.2 × 10−6≤MCO≤ 2.7 × 10−6 M⊙ of CO ejecta outside the dust, forming a high-velocity wind of 500 ± 80 km s−1. We find evidence for significant weakening of the CO band and cooling of the dust around the central star between 2003 and 2005. The gas and dust temperatures are implausibly high for stellar radiation to be the sole contributor

A spectroscopic atlas of post-AGB stars and planetary nebulae selected from the IRAS Point Source Catalogue

Aims: We study the optical spectral properties of a sample of stars showing far infrared colours similar to those of well-known planetary nebulae. The large majority of them were unidentified sources or poorly known in the literature at the time when this spectroscopic survey started, some 15 years ago. Methods: We present low-resolution optical spectroscopy, finding charts and improved astrometric coordinates of a sample of 253 IRAS sources. Results: We have identified 103 sources as post-AGB stars, 21 as ``transition sources'', and 36 as planetary nebulae, some of them strongly reddened. Among the rest of sources in the sample, we were also able to identify 38 young stellar objects, 5 peculiar stars, and 2 Seyfert galaxies. Up to 49 sources in our spectroscopic sample do not show any optical counterpart, and most of them are suggested to be heavily obscured post-AGB stars, rapidly evolving on their way to becoming planetary nebulae. Conclusions: An analysis of the galactic distribution of the sources identified as evolved stars in the sample is presented together with a study of the distribution of these stars in the IRAS two-colour diagram. Finally, the spectral type distribution and other properties of the sources identified as post-AGB in this spectroscopic survey are discussed in the framework of stellar evolution.Comment: 69 pages, 413 figures. Accepted by Astronomy and Astrophysic

Stellar wind bubbles around WR and [WR] stars

We study the dynamics of stellar wind bubbles around hydrogen-deficient stars using numerical simulations with time- and ion dependent cooling. We consider two types of hydrogen-deficient stars, massive WR stars, producing Ring Nebulae, and low mass [WR] stars, producing Planetary Nebulae. We show that for the Planetary Nebulae, the different cooling properties of the hydrogen-deficient wind lead to a later transition from momentum- to energy-driven flow, which could explain the observed turbulence of these nebulae. We find that Ring Nebulae should all be energy-driven, and show how comparing the bubble's momentum and kinetic energy to the input wind momentum and kinetic energy, can give misleading information about the dynamics of the bubble.Comment: 9 pages, 3 figures, to be published in A&

Automated PGP9.5 immunofluorescence staining: a valuable tool in the assessment of small fiber neuropathy?

BACKGROUND: In this study we explored the possibility of automating the PGP9.5 immunofluorescence staining assay for the diagnosis of small fiber neuropathy using skin punch biopsies. The laboratory developed test (LDT) was subjected to a validation strategy as required by good laboratory practice guidelines and compared to the well-established gold standard method approved by the European Federation of Neurological Societies (EFNS). To facilitate automation, the use of thinner sections. (16 µm) was evaluated. Biopsies from previously published studies were used. The aim was to evaluate the diagnostic performance of the LDT compared to the gold standard. We focused on technical aspects to reach high-quality standardization of the PGP9.5 assay and finally evaluate its potential for use in large scale batch testing. RESULTS: We first studied linear nerve fiber densities in skin of healthy volunteers to establish reference ranges, and compared our LDT using the modifications to the EFNS counting rule to the gold standard in visualizing and quantifying the epidermal nerve fiber network. As the LDT requires the use of 16 µm tissue sections, a higher incidence of intra-epidermal nerve fiber fragments and a lower incidence of secondary branches were detected. Nevertheless, the LDT showed excellent concordance with the gold standard method. Next, the diagnostic performance and yield of the LDT were explored and challenged to the gold standard using skin punch biopsies of capsaicin treated subjects, and patients with diabetic polyneuropathy. The LDT reached good agreement with the gold standard in identifying small fiber neuropathy. The reduction of section thickness from 50 to 16 µm resulted in a significantly lower visualization of the three-dimensional epidermal nerve fiber network, as expected. However, the diagnostic performance of the LDT was adequate as characterized by a sensitivity and specificity of 80 and 64 %, respectively. CONCLUSIONS: This study, designed as a proof of principle, indicated that the LDT is an accurate, robust and automated assay, which adequately and reliably identifies patients presenting with small fiber neuropathy, and therefore has potential for use in large scale clinical studies

The Mid-Infrared Colours of Galactic Bulge, Disk and Magellanic Planetary Nebulae

We present mid-infrared (MIR) photometry for 367 Galactic disk, bulge and Large Magellanic Cloud (LMC) planetary nebulae, determined using GLIMPSE II and SAGE data acquired using the Spitzer Space Telescope. This has permitted us to make a comparison between the luminosity functions of bulge and LMC planetary nebulae, and between the MIR colours of all three categories of source. It is determined that whilst the 3.6 microns luminosity function of the LMC and bulge sources are likely to be closely similar, the [3.6]-[5.8] and [5.8]-[8-0] indices of LMC nebulae are different from those of their disk and bulge counterparts. This may arise because of enhanced 6.2 microns PAH emission within the LMC sources, and/or as a result of differences between the spectra of LMC PNe and those of their Galactic counterparts. We also determine that the more evolved disk sources listed in the MASH catalogues of Parker et al. and Miszalski et al. (2008) have similar colours to those of the less evolved (and higher surface brightness) sources in the catalogue of Acker et al. (1992); a result which appears at variance with previous studies of these sources.Comment: 14 pages, 9 figures, Publicated in MNRAS. 58 pages in arXi

Angular diameters, fluxes and extinction of compact planetary nebulae: further evidence for steeper extinction towards the Bulge

We present values for angular diameter, flux and extinction for 70 Galactic planetary nebulae observed using narrow band filters. Angular diameters are derived using constant emissivity shell and photoionization line emission models. The mean of the results from these two models are presented as our best estimate. Contour plots of 36 fully resolved objects are included and the low intensity contours often reveal an elliptical structure that is not always apparent from FWHM measurements. Flux densities are determined, and for both H-alpha and O[III] there is little evidence of any systematic differences between observed and catalogued values. Observed H-alpha extinction values are determined using observed H-alpha and catalogued radio fluxes. H-alpha extinction values are also derived from catalogued H-alpha and H-beta flux values by means of an Rv dependent extinction law. Rv is then calculated in terms of observed extinction values and catalogued H-alpha and H-beta flux values. Comparing observed and catalogue extinction values for a subset of Bulge objects, observed values tend to be lower than catalogue values calculated with Rv = 3.1. For the same subset we calculate = 2.0, confirming that toward the Bulge interstellar extinction is steeper than Rv = 3.1. For the inner Galaxy a relation with the higher supernova rate is suggested, and that the low-density warm ionized medium is the site of the anomalous extinction. Lowvalues of extinction are also derived using dust models with a turnover radius of 0.08 microns.Comment: Accepted by MNRAS. 17 pages, 9 figures (including 36 contour plots of PNe), 5 Tables (including 2 large tables of angular diameters, fluxes and extinction