Respiratory viral infection in lower airways of asymptomatic children.

Aim: The aim of this study was to determine if asthmatic children have viruses more commonly detected in lower airways during asymptomatic periods than normal children. Methods: Fifty-five asymptomatic children attending elective surgical procedures (14 with stable asthma, 41 normal controls) underwent non-bronchoscopic bronchoalveolar lavage. Differential cell count and PCR for 13 common viruses were performed. Results: Nineteen (35%) children were positive for at least one virus, with adenovirus being most common. No differences in the proportion of viruses detected were seen between asthmatic and normal ‘control’ children. Viruses other than adenovirus were associated with higher neutrophil counts, suggesting that they caused an inflammatory response in both asthmatics and controls (median BAL neutrophil count, 6.9% for virus detected vs. 1.5% for virus not detected, p = 0.03). Conclusions: Over one-third of asymptomatic children have a detectable virus (most commonly adenovirus) in the lower airway; however, this was not more common in asthmatics. Viruses other than adenovirus were associated with elevated neutrophils suggesting that viral infection can be present during relatively asymptomatic periods in asthmatic children.

Respiratory syncytial virus (RSV) vaccines - Two steps back for one leap forward

Respiratory viruses are among the most important causes of morbidity and mortality worldwide. From a vaccine viewpoint, such viruses may be divided into two principle groups-those where infection results in long-term immunity and whose continued survival requires constant mutation, and those where infection induces incomplete immunity and repeated infections are common, even with little or no mutation. Influenza virus and respiratory syncytial virus (RSV) typify the former and latter groups, respectively. Importantly, successful vaccines have been developed against influenza virus. However, this is not the case for RSV, despite many decades of research and several vaccine approaches. Similar to natural infection, the principle limitation of candidate RSV vaccines in humans is limited immunogenicity, characterised in part by short-term RSV-specific adaptive immunity. The specific reasons why natural RSV infection is insufficiently immunogenic in humans are unknown but circumvention of innate and adaptive immune responses are likely causes. Fundamental questions concerning RSV/host interactions remain to be addressed at both the innate and adaptive immune levels in humans in order to elucidate mechanisms of immune response circumvention. Taking the necessary steps back to generate such knowledge will provide the means to leap forward in our quest for a successful RSV vaccine. Recent developments relating to some of these questions are discussed. (C) 2007 Elsevier B.V. All rights reserved.

Respiratory syncytial virus NS1 protein degrades STAT2 by using the elongin-cullin E3 ligase

Respiratory syncytial virus (RSV) infection causes bronchiolitis and pneumonia in infants. RSV has a linear single-stranded RNA genome encoding 11 proteins, 2 of which are nonstructural (NS1 and NS2). RSV specifically downregulates STAT2 protein expression, thus enabling the virus to evade the host type I interferon response. Degradation of STAT2 requires proteasomal activity and is dependent on the expression of RSV NS1 and NS2 (NS1/2). Here we investigate whether RSV NS proteins can assemble ubiquitin ligase (E3) enzymes to target STAT2 to the proteasome. We demonstrate that NS1 contains elongin C and cullin 2 binding consensus sequences and can interact with elongin C and cullin 2 in vitro; therefore, NS1 has the potential to act as an E3 ligase. By knocking down expression of specific endogenous E3 ligase components using small interfering RNA, NS1/2, or RSV-induced STAT2, degradation is prevented. These results indicate that E3 ligase activity is crucial for the ability of RSV to degrade STAT2. These data may provide the basis for therapeutic intervention against RSV and/or logically designed live attenuated RSV vaccines.

The respiratory syncytial virus small hydrophobic protein is phosphorylated via a mitogen-activated protein kinase p38-dependent tyrosine kinase activity during virus infection

The phosphorylation status of the small hydrophobic (SH) protein of respiratory syncytial virus (RSV) was examined in virus-infected Vero cells. The SH protein v.,as isolated from [S-35]methionine- and [P-33]orthophosphate-labelled IRSV-infected cells and analysed by SDS-PAGE. In each case, a protein product of the expected size for the SH protein was observed. Phosphoamino acid analysis and reactivity with the phosphotyrosine specific antibody PY20 showed that the SH protein was modified by tyrosine phosphorylation. The role or tyrosine kinase activity in SH protein phosphorylation was confirmed by the use of genistein, a broad-spectrum tyrosine kinase inhibitor, to inhibit SH protein phosphorylation. Further analysis showed that the different glycosylated forms of the SH protein were phosphorylated, as was the oligomeric form of the protein. Phosphorylation of the SH protein was specifically inhibited by the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580, suggesting that SH protein phosphorylation occurs via a MAPK p38-dependent pathway. Analysis of virus-infected cells using fluorescence microscopy showed that, although the SH protein was distributed throughout the cytoplasm, it appeared to accumulate, at low levels, in the endoplasmic reticulum/Golgi complex, confirming recent observations. However, in the presence of SB203580. an increased accumulation of the SH protein in the Golgi complex was observed, although other virus structures, such as virus filaments and inclusion bodies, remained largely unaffected. These results showed that during RSV infection, the SH protein is modified by an MAPK p38-dependant tyrosine kinase activity and that this modification influences its cellular distribution.

Abell 41: shaping of a planetary nebula by a binary central star

ABSTRACT We present the first detailed spatiokinematical analysis and modelling of the planetary nebula Abell 41, which is known to contain the well-studied close-binary system MT Ser. This object represents an important test case in the study of the evolution of planetary nebulae with binary central stars as current evolutionary theories predict that the binary plane should be aligned perpendicular to the symmetry axis of the nebula. Deep narrow-band imaging in the light of [NII]6584Å, [OIII]5007 Å and [SII]6717+6731Å, obtained using ACAM on the William Herschel Telescope, has been used to investigate the ionization structure of Abell 41. Long-slit observations of the Ha and [NII]6584Å emission were obtained using the Manchester Echelle Spectrometer on the 2.1-m San Pedro Mártir Telescope. These spectra, combined with the narrow-band imagery, were used to develop a spatiokinematical model of [NII]6584Å emission from Abell 41. The best-fitting model reveals Abell 41 to have a waisted, bipolar structure with an expansion velocity of ~40 km s-1 at the waist. The symmetry axis of the model nebula is within 5° of perpendicular to the orbital plane of the central binary system. This provides strong evidence that the close-binary system, MT Ser, has directly affected the shaping of its nebula, Abell 41. Although the theoretical link between bipolar planetary nebulae and binary central stars is long established, this nebula is only the second to have this link, between nebular symmetry axis and binary plane, proved observationally.

Supplemental oxygen and hyperbaric treatment at high altitude: Cardiac and respiratory response

Introduction: The most effective treatment for high altitude sickness is prompt descent. However, rapid descent is sometimes impossible and alternative solutions are desirable. Supplemental oxygen at ambient pressure and hyperbaric oxygen in a hyperbaric tent have both been demonstrated to improve symptoms and increase arterial oxygenation (SaO(2)) in those with high altitude sickness; however, their use in combination has not previously been described in a controlled study. Methods and Results: In this feasibility study, the SaO(2) of six healthy, well-acclimatized participants rose from 76.5 to 97.5% at 4900 m and 72.5 to 96.0% at 5700 m following the administration of oxygen via a nasal demand circuit (33 ml of oxygen per pulse) inside a hyperbaric tent (107 mmHg above ambient barometric pressure) (p

The symbolization of central approximants in the IPA

Approximants that can be considered weaker versions of voiced fricatives (termed here ‘frictionless continuants’) are poorly served by the IPA in terms of symbolization as compared to semi-vowel approximants. In this paper we survey the central approximants and the symbols and diacritics used to transcribe them; we focus on evidence for the use of non-rhotic frictionless continuants in both natural language (by which we mean non-clinical varieties) and disordered speech; and we suggest some possible unitary symbols for those that currently require the use of a hard-to-read lowering diacritic beneath the symbol for the corresponding voiced fricative.