958 research outputs found
Autoantibodies against cardiac β(1)-adrenoceptor do not affect the low-affinity state β(1)-adrenoceptor-mediated inotropy in rat cardiomyocytes
Circulating autoantibodies directed against the 2nd extracellular loop (EL-2) of β(1)-adrenoceptors (β(1)-AABs) have been detected in the serum of patients with various cardiovascular pathologies. β(1)-AABs induce agonistic, positive inotropic effects via β(1)-adrenoceptors (β(1)ARs). In the mammalian heart, β(1)-AR can exist in 2 distinct activated configurations (the so-called high- and low-affinity states). The aim of the present study was to investigate whether the action of β(1)-AAB is dependent on the affinity state of β(1)AR in isolated ventricular cardiomyocytes of adult Wistar rats. Immunoglobulin G (IgG) containing β(1)-AAB obtained from animals immunized with a peptide corresponding to the EL-2 of human β(1)-AR, caused a dose-dependent increase in cell shortening. Isoproterenol-induced inotropy was significantly reduced in cardiomyocytes that had been preincubated with IgG containing β(1)-AAB and in cardiomyocytes isolated from immunized rats. The negative effects of preincubation with IgG containing β(1)-AAB on the response to isoproterenol was inhibited in the presence of bisoprolol. CGP 12177A and pindolol-induced inotropy was not affected by IgG preincubation or immunization. No detectable inotropic effect of cell shortening was obtained with IgG containing β(1)-AAB in the presence of propranolol and 3-isobutyl-1-methylxanthine. The present study demonstrates that β(1)-AABs have no agonist/antagonist-like effects upon low-affinity state β(1)-ARs. This result indicates that β(1)-AABs recognize and stabilize the high-affinity state, but are unable to stabilize and (or) induce the low-affinity state receptor
Vasodilatory effect of pentoxifylline in isolated equine digital veins
The direct vasodilatory action of pentoxifylline (1-(5-oxohexyl)-3,7-dimethylxanthine) and its signalling pathway was evaluated in equine digital veins. Cumulative concentration-response curves to pentoxifylline (1 nM to 300 ÎźM) were recorded in phenylephrine-precontracted equine digital vein rings under different experimental conditions. Relaxation to pentoxifylline was partially inhibited by endothelium removal, but was unaltered by CGS-15943 (a non-xanthine adenosine receptor antagonist; 3 ÎźM). Nitric oxide synthase (NOS), soluble guanylate cyclase and cyclooxygenase (COX) inhibitors (NĎ-nitro-L-arginine methyl ester (100 ÎźM), ODQ (30 ÎźM) and indomethacin (10 ÎźM), respectively) significantly reduced the maximum relaxation induced by pentoxifylline. Moreover, pentoxifylline-induced relaxation was strongly reduced by Rp-8-Br-PET-cyclic guanosine monophosphate-S (a protein kinase G inhibitor; 3 ÎźM), but remained unaffected by H-89 (a protein kinase A inhibitor; 2 ÎźM). Pentoxifylline-induced relaxation was associated with a 3.4-fold increase in tissue cGMP content. To investigate whether pentoxifylline can affect cAMP- and cGMP-mediated relaxations, curves to forskolin, to sodium nitroprusside (SNP) and 8-bromo-cGMP were also recorded in endothelium-denuded equine digital vein rings pretreated with pentoxifylline (10 and 100 ÎźM). Pentoxifylline only potentiated the SNP-mediated relaxation at the highest concentration (100 ÎźM). Thus, pentoxifylline relaxed equine digital veins via endothelium-dependent and endothelium-independent components. The effect was mediated through both the NOS and COX pathways and could also result from inhibition of cGMP specific-phosphodiesterase activity at the highest concentrations used
Antibodies against the second extracellular loop of β1-adrenergic receptors induce endothelial dysfunction in conductance and resistance arteries of the Wistar rat
Autoantibodies against β1-adrenoceptors (β1-ARs) have been detected in the serum of patients with various cardiac diseases; however, the pathological impact of these autoantibodies (β1-AABs) has only been evaluated in cardiac tissue. The purpose of the present study was to evaluate whether β1-AABs have deleterious effects on vascular reactivity in rats.
An enzyme-linked immunosorbent assay was used to detect β1-AABs in sera from immunized rats over a period of 1â3 months using the peptidic sequence of the second extracellular loop of human β1-AR. Functional studies were performed in thoracic aortic (TA) and small mesenteric artery (SMA) rings from immunized rats. Following pre-contraction with phenylephrine (0.3 ΟM and 3 ΟM for the TA and SMA respectively), cumulative concentrationâresponse curves (CCRCs) to various β-AR agonists (isoproterenol, dobutamine, salbutamol, SR 58611A), acetylcholine, A23187, and sodium nitroprusside (SNP) were then plotted.
The relaxations induced by dobutamine, SR 58611A, and acetylcholine were significantly impaired, but salbutamol-induced relaxations were not affected, in both vessels from immunized rats. A significant impairment of isoproterenol-induced relaxation was only observed in SMA. CCRCs to SNP were not modified in either of the vessels. A23187-induced relaxation was impaired in immunized rats. Following pretreatment with l-arginine, vasorelaxation to acetylcholine and SR 58611A was restored in immunized rats.
This study demonstrates that immunization against the second extracellular loop of β1-ARs has a deleterious impact on vasorelaxations in the TA and SMA of rats, involving alterations in endothelium-dependent NO signaling pathways
Photoproduction of K+Kâ meson pairs on the proton
The exclusive reaction ÎłpâpK+Kâ was studied in the photon energy range 3.0â3.8ââGeV and momentum transfer range 0.6<ât<1.3ââGeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. In this kinematic range the integrated luminosity was approximately 20ââpbâ1. The reaction was isolated by detecting the K+ and the proton in CLAS, and reconstructing the Kâ via the missing-mass technique. Moments of the dikaon decay angular distributions were extracted from the experimental data. Besides the dominant contribution of the Ď meson in the P wave, evidence for SâP interference was found. The differential production cross sections dĎ/dt for individual waves in the mass range of the Ď resonance were extracted and compared to predictions of a Regge-inspired model. This is the first time the t-dependent cross section of the S-wave contribution to the elastic K+Kâ photoproduction has been measured
The CLAS12 software framework and event reconstruction
We describe offline event reconstruction for the CEBAF Large Acceptance Spectrometer at 12Â GeV (CLAS12), including an overview of the offline reconstruction framework and software tools, a description of the algorithms developed for the individual detector subsystems, and the overall approach for charged and neutral particle identification. We also present the scheme for data processing and the code management procedures
Quantitative promoter methylation differentiates carcinoma ex pleomorphic adenoma from pleomorphic salivary adenoma
Beam Charge Asymmetries for Deeply Virtual Compton Scattering on the Proton at CLAS12
The parameterization of the nucleon structure through Generalized Parton
Distributions (GPDs) shed a new light on the nucleon internal dynamics. For its
direct interpretation, Deeply Virtual Compton Scattering (DVCS) is the golden
channel for GPDs investigation. The DVCS process interferes with the
Bethe-Heitler (BH) mechanism to constitute the leading order amplitude of the
process. The study of the reaction with polarized
positron and electron beams gives a complete set of unique observables to
unravel the different contributions to the cross section. This
separates the different reaction amplitudes, providing a direct access to their
real and imaginary parts which procures crucial constraints on the model
dependences and associated systematic uncertainties on GPDs extraction. The
real part of the BH-DVCS interference amplitude is particularly sensitive to
the -term which parameterizes the Gravitational Form Factors of the nucleon.
The separation of the imaginary parts of the interference and DVCS amplitudes
provides insights on possible higher-twist effects. We propose to measure the
unpolarized and polarized Beam Charge Asymmetries (BCAs) of the process on an unpolarized hydrogen target with {\tt
CLAS12}, using polarized positron and electron beams at 10.6~GeV. The azimuthal
and -dependences of the unpolarized and polarized BCAs will be measured over
a large phase space using a 100 day run with a luminosity of
0.66cms.Comment: Proposal to the Jefferson Lab Program Advisory Committee (PAC51
First Measurement of Hard Exclusive Ď- Î++ Electroproduction Beam-Spin Asymmetries off the Proton
The polarized cross-section ratio ĎLTâ˛/Ď0 from hard exclusive Ď-Î++ electroproduction off an unpolarized hydrogen target has been extracted based on beam-spin asymmetry measurements using a 10.2 GeV/10.6 GeV incident electron beam and the CLAS12 spectrometer at Jefferson Lab. The study, which provides the first observation of this channel in the deep-inelastic regime, focuses on very forward-pion kinematics in the valence regime, and photon virtualities ranging from 1.5 GeV2 up to 7 GeV2. The reaction provides a novel access to the d-quark content of the nucleon and to pâÎ++ transition generalized parton distributions. A comparison to existing results for hard exclusive Ď+n and Ď0p electroproduction is provided, which shows a clear impact of the excitation mechanism, encoded in transition generalized parton distributions, on the asymmetry
First measurements of the double-polarization observables F, P, and H in Ď photoproduction off transversely polarized protons in the N* resonance region
First measurements of double-polarization observables in Ď photoproduction off the proton are presented using transverse target polarization and data from the CEBAF Large Acceptance Spectrometer (CLAS) FROST experiment at Jefferson Lab. The beam-target asymmetry F has been measured using circularly polarized, tagged photons in the energy range 1200â2700 MeV, and the beam-target asymmetries H and P have been measured using linearly polarized, tagged photons in the energy range 1200â2000 MeV. These measurements significantly increase the database on polarization observables. The results are included in two partial-wave analyses and reveal significant contributions from several nucleon (Nâ) resonances. In particular, contributions from new Nâ resonances listed in the Review of Particle Properties are observed, which aid in reaching the goal of mapping out the nucleon resonance spectrum
Measurement of the helicity asymmetry E for the Îłâ pâ â pĎ reaction in the resonance region: The CLAS Collaboration
The double-spin-polarization observable E for Îłâ pâ â pĎ has been measured with the CEBAF Large Acceptance Spectrometer (CLAS) at photon beam energies EÎł from 0.367 to 2.173GeV (corresponding to center-of-mass energies from 1.240 to 2.200GeV) for pion center-of-mass angles, cosθĎ0c.m. , between - 0.86 and 0.82. These new CLAS measurements cover a broader energy range and have smaller uncertainties compared to previous CBELSA data and provide an important independent check on systematics. These measurements are compared to predictions as well as new global fits from The George Washington University, Mainz, and Bonn-Gatchina groups. Their inclusion in multipole analyses will allow us to refine our understanding of the single-pion production contribution to the Gerasimov-Drell-Hearn sum rule and improve the determination of resonance properties, which will be presented in a future publication
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