483 research outputs found
Tachykinin receptors antagonism for asthma: a systematic review
<p>Abstract</p> <p>Background</p> <p>Tachykinins substance P, neurokinin A and neurokinin B seem to account for asthma pathophysiology by mediating neurogenic inflammation and several aspects of lung mechanics. These neuropeptides act mainly by their receptors NK1, NK2 and NK3, respectively which may be targets for new asthma therapy.</p> <p>Methods</p> <p>This review systematically examines randomized controlled trials evaluating the effect of tachykinins receptors antagonism on asthma. Symptoms, airway inflammation, lung function and airway inflammation were considered as outcomes. We searched the Cochrane Airways Group Specialized Register of Asthma Trials, Cochrane Database of Systematic Reviews, MEDLINE/PubMed and EMBASE. The search is as current as June 2010. Quality rating of included studies followed the Cochrane Collaboration and GRADE Profiler approaches. However, data were not pooled together due to different measures among the studies.</p> <p>Results</p> <p>Our systematic review showed the potential of NK receptor antagonist to decrease airway responsiveness and to improve lung function. However, effects on airway inflammation and asthma symptoms were poorly or not described.</p> <p>Conclusion</p> <p>The limited available evidence suggests that tachykinin receptors antagonists may decrease airway responsiveness and improve lung function in patients with asthma. Further large randomized trials are still required.</p
Pharmacogenomics of Interferon-ß Therapy in Multiple Sclerosis: Baseline IFN Signature Determines Pharmacological Differences between Patients
Multiple sclerosis (MS) is a heterogeneous disease. In order to understand the partial responsiveness to IFNbeta in Relapsing Remitting MS (RRMS) we studied the pharmacological effects of IFNbeta therapy. Large scale gene expression profiling was performed on peripheral blood of 16 RRMS patients at baseline and one month after the start of IFNbeta therapy. Differential gene expression was analyzed by Significance Analysis of Microarrays. Subsequent expression analyses on specific genes were performed after three and six months of treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated in vitro with IFNbeta. Genes of interest were measured and validated by quantitative realtime PCR. An independent group of 30 RRMS patients was used for validation. Pharmacogenomics revealed a marked variation in the pharmacological response to IFNbeta between patients. A total of 126 genes were upregulated in a subset of patients whereas in other patients these genes were downregulated or unchanged after one month of IFNbeta therapy. Most interestingly, we observed that the extent of the pharmacological response correlates negatively with the baseline expression of a specific set of 15 IFN response genes (R = -0.7208; p = 0.0016). The negative correlation was maintained after three (R = -0.7363; p = 0.0027) and six (R = -0.8154; p = 0.0004) months of treatment, as determined by gene expression levels of the most significant correlating gene. Similar results were obtained in an independent group of patients (n = 30; R = -0.4719; p = 0.0085). Moreover, the ex vivo results could be confirmed by in vitro stimulation of purified PBMCs at baseline with IFNbeta indicating that differential responsiveness to IFNbeta is an intrinsic feature of peripheral blood cells at baseline. These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNbet
Characterisation of a divergent progenitor cell sub-populations in human osteoarthritic cartilage: the role of telomere erosion and replicative senescence
In recent years it has become increasingly clear that articular cartilage harbours a viable pool ofprogenitor cells and interest has focussed on their role during development and disease. Analysis ofprogenitor numbers using fluorescence-activated sorting techniques has resulted in wide-rangingestimates, which may be the result of context-dependent expression of cell surface markers. Wehave used a colony-forming assay to reliably determine chondroprogenitor numbers in normal andosteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P < 0.0001). Intriguingly,cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilagerevealed the presence of a divergent progenitor subpopulation characterised by an early senescentphenotype. Divergent sub-populations displayed increased senescence-associated β–galactosidaseactivity, lower average telomere lengths but retained the capacity to undergo multi-lineagedifferentiation. Osteoarthritis is an age-related disease and cellular senescence is predicted to be asignificant component of the pathological process. This study shows that although early senescenceis an inherent property of a subset of activated progenitors, there is also a pool of progenitors withextended viability and regenerative potential residing within osteoarthritic cartilage
Precision measurement of the top quark mass from dilepton events at CDF II
We report a measurement of the top quark mass, M_t, in the dilepton decay
channel of
using an integrated luminosity of 1.0 fb^{-1} of p\bar{p} collisions collected
with the CDF II detector. We apply a method that convolutes a leading-order
matrix element with detector resolution functions to form event-by-event
likelihoods; we have enhanced the leading-order description to describe the
effects of initial-state radiation. The joint likelihood is the product of the
likelihoods from 78 candidate events in this sample, which yields a measurement
of M_{t} = 164.5 \pm 3.9(\textrm{stat.}) \pm 3.9(\textrm{syst.})
\mathrm{GeV}/c^2, the most precise measurement of M_t in the dilepton channel.Comment: 7 pages, 2 figures, version includes changes made prior to
publication by journa
Measurement of the Ratios of Branching Fractions B(Bs -> Ds pi pi pi) / B(Bd -> Dd pi pi pi) and B(Bs -> Ds pi) / B(Bd -> Dd pi)
Using 355 pb^-1 of data collected by the CDF II detector in \ppbar collisions
at sqrt{s} = 1.96 TeV at the Fermilab Tevatron, we study the fully
reconstructed hadronic decays B -> D pi and B -> D pi pi pi. We present the
first measurement of the ratio of branching fractions B(Bs -> Ds pi pi pi) /
B(Bd -> Dd pi pi pi) = 1.05 pm 0.10 (stat) pm 0.22 (syst). We also update our
measurement of B(Bs -> Ds pi) / B(Bd -> Dd pi) to 1.13 pm 0.08 (stat) pm 0.23
(syst) improving the statistical uncertainty by more than a factor of two. We
find B(Bs -> Ds pi) = [3.8 pm 0.3 (stat) pm 1.3 (syst)] \times 10^{-3} and B(Bs
-> Ds pi pi pi) = [8.4 pm 0.8 (stat) pm 3.2 (syst)] \times 10^{-3}.Comment: 7 pages, 2 figure
Cross Section Measurements of High- Dilepton Final-State Processes Using a Global Fitting Method
We present a new method for studying high- dilepton events
(, , ) and simultaneously
extracting the production cross sections of , , and p\bar{p} \to \ztt at a center-of-mass energy of TeV. We perform a likelihood fit to the dilepton data in a parameter
space defined by the missing transverse energy and the number of jets in the
event. Our results, which use of data recorded with the CDF
II detector at the Fermilab Tevatron Collider, are pb, pb, and
\sigma(\ztt) =291^{+50}_{-46} pb.Comment: 20 pages, 2 figures, to be submitted to PRD-R
Measurement of the Lambda_b Lifetime in Lambda_b --> J/psi Lambda0 in p-pbar Collisions at sqrt(s)=1.96 TeV
We report a measurement of the Lambda_b lifetime in the exclusive decay
Lambda_b --> J/psi Lambda0 in p-pbar collisions at sqrt(s) = 1.96 TeV using an
integrated luminosity of 1.0 fb^{-1} of data collected by the CDF II detector
at the Fermilab Tevatron. Using fully reconstructed decays, we measure
tau(Lambda_b) = 1.593 ^{+0.083}_{-0.078} (stat.) +- 0.033 (syst.) ps. This is
the single most precise measurement of tau(Lambda_b) and is 3.2 sigma higher
than the current world average.Comment: 7 Pages, 2 Figures, 1 Table. Submitted to Phys. Rev. Let
Observation of WZ Production
We report the first observation of the associated production of a W boson and
a Z boson. This result is based on 1.1 fb-1 of integrated luminosity from ppbar
collisions at sqrt{s} = 1.96 TeV collected with the CDF II detector at the
Fermilab Tevatron. We observe 16 WZ candidates passing our event selection with
an expected background of 2.7 +/- 0.4 events. A fit to the missing transverse
energy distribution indicates an excess of events compared to the background
expectation corresponding to a significance equivalent to six standard
deviations. The measured cross section is sigma(ppbar -> WZ) =
5.0^{+1.8}_{-1.6} pb, consistent with the standard model expectation.Comment: 7 pages, 3 figures. Submitted to Phys. Rev. Let
Measurement of the Top-Quark Mass in All-Hadronic Decays in p pbar Collisions at CDF II
We present a measurement of the top-quark mass, , in the
all-hadronic decay channel . The analysis is performed using 310 pb of
=1.96 TeV collisions collected with the CDF II detector
using a multi-jet trigger. The mass measurement is based on an event-by-event
likelihood which depends on both the sample purity and the value of the
top-quark mass, using 90 possible jet-to-parton assignments in the six-jet
final state. The joint likelihood of 290 selected events yields a value of
=177.1 4.9 (stat.) 4.7 (syst.) GeV/.Comment: 7 pages, 2 figures and 1 table, Submitted to Phys. Rev. Let
Analysis of the Quantum Numbers of the X(3872) Particle
We present an analysis of angular distributions and correlations of the
X(3872) particle in the exclusive decay mode X(3872)->J/psi pi+ pi- with
J/psi->mu+ mu-. We use 780 pb -1 of data from ppbar collisions at sqrt{s} =
1.96 TeV collected with the CDF II detector at the Fermilab Tevatron. We derive
constraints on spin, parity, and charge conjugation parity of the X(3872)
particle by comparing measured angular distributions of the decay products with
predictions for different JPC hypotheses. The assignments JPC = 1++ and 2-+ are
the only ones consistent with the data.Comment: update to journal versio
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