942 research outputs found
Eosinophil and T Cell Markers Predict Functional Decline in COPD Patients
BACKGROUND. The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. METHODS. Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ÎFEV1 % predicted = 4.7 Âą 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ÎFEV1 % predicted = -16.0 Âą 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. RESULTS AND DISCUSSION. Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). CONCLUSION. These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.National Heart, Lung, and Blood Institute (NO1-HR-96140, NO1-HR-96141-001, NO1-HR-96144, NO1-HR-96143; NO1-HR-96145; NO1-HR-96142, R01HL086936-03); The Flight Attendant Medical Research Institute; the Jo-Ann F. LeBuhn Center for Chest Diseas
The house dust mite allergen Der p 5 binds lipid ligands and stimulates airway epithelial cells through a TLR2âdependent pathway
Background:
Protein crystallographic studies suggest that the house dust mite (HDM) allergen Der p 5 potentially interacts with hydrophobic ligands. Der p 5, in association with its ligand(s), might therefore trigger innate immune signalling pathways in the airway epithelium and influence the initiation of the HDMâallergic response.
Objective:
We investigated the lipid binding propensities of recombinant (r)Der p 5 and characterized the signalling pathways triggered by the allergen in airway epithelial cells.
Methods:
rDer p 5 was produced in Pichia pastoris and characterized by mass spectrometry, multiâangle light scattering and circular dichroism. Its interactions with hydrophobic ligands were investigated in fluorescenceâbased lipid binding assays and inâsilico docking simulations. Innate immune signalling pathways triggered by rDer p 5 were investigated in airway epithelial cell activation assays in vitro.
Results:
Biophysical analysis showed that rDer p 5 was monomeric and adopted a similar Îąâhelixârich fold at both physiological and acidic pH. Spectrofluorimetry experiments showed that rDer p 5 is able to selectively bind lipid ligands, but only under mild acidic pH conditions. Computerâbased docking simulations identified potential binding sites for these ligands. This allergen, with putatively associated lipid(s), triggered the production of ILâ8 in respiratory epithelial cells through a TLR2â, NFâkBâ and MAPKâdependent signalling pathway.
Conclusions and Clinical Relevance:
Despite the fact that Der p 5 represents a HDM allergen of intermediate prevalence, our findings regarding its lipid binding and activation of TLR2 indicate that it could participate in the initiation of the HDMâallergic state
Display of native antigen on cDC1 that have spatial access to both T and B cells underlies efficient humoral vaccination
Follicular dendritic cells and macrophages have been strongly implicated in presentation of native Ag to B cells. This property has also occasionally been attributed to conventional dendritic cells (cDC) but is generally masked by their essential role in T cell priming. cDC can be divided into two main subsets, cDC1 and cDC2, with recent evidence suggesting that cDC2 are primarily responsible for initiating B cell and T follicular helper responses. This conclusion is, however, at odds with evidence that targeting Ag to Clec9A (DNGR1), expressed by cDC1, induces strong humoral responses. In this study, we reveal that murine cDC1 interact extensively with B cells at the border of B cell follicles and, when Ag is targeted to Clec9A, can display native Ag for B cell activation. This leads to efficient induction of humoral immunity. Our findings indicate that surface display of native Ag on cDC with access to both T and B cells is key to efficient humoral vaccination
Assessment of Survivor Concerns (ASC): A newly proposed brief questionnaire
BACKGROUND: The purpose of this study was to design a brief questionnaire to measure fears about recurrence and health in cancer survivors. Research involving fear of recurrence has been increasing, indicating that it is an important concern among cancer survivors. METHODS: We developed and tested a six-item instrument, the Assessment of Survivor Concerns (ASC). Construct validity was examined in a multiple group confirmatory factor analysis (CFA) with 592 short-term and 161 long-term cancer survivors. Convergent and discriminant validity was examined through comparisons with the PANAS (Positive and Negative Affect Schedule) and the CES-D (Center for Epidemiologic Studies Depression) measures. RESULTS: CFA models for the ASC with short- and long-term survivors showed good fit, with equivalent structure across both groups of cancer survivors. Convergent and discriminant validity was also supported through analyses of the PANAS and CES-D. One item (children's health worry) did not perform as well as the others, so the models were re-run with the item excluded, and the overall fit was improved. CONCLUSION: The ASC showed excellent internal consistency and validity. We recommend the revised five-item instrument as an appropriate measure for assessment of cancer survivor worries
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory
The advent of the Auger Engineering Radio Array (AERA) necessitates the
development of a powerful framework for the analysis of radio measurements of
cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air
shower radio emission in coincidence with the surface particle detectors and
fluorescence telescopes of the Pierre Auger Observatory, the radio analysis
functionality had to be incorporated in the existing hybrid analysis solutions
for fluoresence and surface detector data. This goal has been achieved in a
natural way by extending the existing Auger Offline software framework with
radio functionality. In this article, we lay out the design, highlights and
features of the radio extension implemented in the Auger Offline framework. Its
functionality has achieved a high degree of sophistication and offers advanced
features such as vectorial reconstruction of the electric field, advanced
signal processing algorithms, a transparent and efficient handling of FFTs, a
very detailed simulation of detector effects, and the read-in of multiple data
formats including data from various radio simulation codes. The source code of
this radio functionality can be made available to interested parties on
request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to
author list and references in v
Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory
We present the results of searches for dipolar-type anisotropies in different
energy ranges above eV with the surface detector array of
the Pierre Auger Observatory, reporting on both the phase and the amplitude
measurements of the first harmonic modulation in the right-ascension
distribution. Upper limits on the amplitudes are obtained, which provide the
most stringent bounds at present, being below 2% at 99% for EeV
energies. We also compare our results to those of previous experiments as well
as with some theoretical expectations.Comment: 28 pages, 11 figure
Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV
The performance of muon reconstruction, identification, and triggering in CMS
has been studied using 40 inverse picobarns of data collected in pp collisions
at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection
criteria covering a wide range of physics analysis needs have been examined.
For all considered selections, the efficiency to reconstruct and identify a
muon with a transverse momentum pT larger than a few GeV is above 95% over the
whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4,
while the probability to misidentify a hadron as a muon is well below 1%. The
efficiency to trigger on single muons with pT above a few GeV is higher than
90% over the full eta range, and typically substantially better. The overall
momentum scale is measured to a precision of 0.2% with muons from Z decays. The
transverse momentum resolution varies from 1% to 6% depending on pseudorapidity
for muons with pT below 100 GeV and, using cosmic rays, it is shown to be
better than 10% in the central region up to pT = 1 TeV. Observed distributions
of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO
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