64 research outputs found

    A novel mutation of the calcium sensing receptor gene is associated with chronic pancreatitis in a family with heterozygous SPINK1 mutations

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    BACKGROUND: The role of mutations in the serine protease inhibitor Kazal type 1 (SPINK1) gene in chronic pancreatitis is still a matter of debate. Active SPINK1 is thought to antagonize activated trypsin. Cases of SPINK1 mutations, especially N34S, have been reported in a subset of patients with idiopathic chronic pancreatitis. However, the inheritance pattern is still unknown. Some cases with N34S heterozygosity have been reported with and without evidence for CP indicating neither an autosomal recessive nor dominant trait. Therefore SPINK1 mutations have been postulated to act as a disease modifier requiring additional mutations in a more complex genetic model. Familial hypocalciuric hypercalcemia (FHH) caused by heterozygous inactivating mutations in the calcium sensing receptor (CASR) gene is considered a benign disorder with elevated plasma calcium levels. Although hypercalcemia represents a risk factor for pancreatitis, increased rates of pancreatitis in patients with FHH have not been reported thus far. METHODS: We studied a family with a FHH-related hypercalcemia and chronic pancreatitis. DNA samples were analysed for mutations within the cationic trypsinogen (N29I, R122H) and SPINK1 (N34S) gene using melting curve analysis. Mutations within CASR gene were identified by DNA sequencing. RESULTS: A N34S SPINK1 mutation was found in all screened family members. However, only two family members developed chronic pancreatitis. These patients also had FHH caused by a novel, sporadic mutation in the CASR gene (518T>C) leading to an amino acid exchange (leucine->proline) in the extracellular domain of the CASR protein. CONCLUSION: Mutations in the calcium sensing receptor gene might represent a novel as yet unidentified predisposing factor which may lead to an increased susceptibility for chronic pancreatitis. Moreover, this family analysis supports the hypothesis that SPINK1 mutations act as disease modifier and suggests an even more complex genetic model in SPINK1 related chronic pancreatitis

    Functional Expression of the Extracellular Calcium Sensing Receptor (CaSR) in Equine Umbilical Cord Matrix Size-Sieved Stem Cells

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    The present study investigates the effects of high external calcium concentration ([Ca(2+)](o)) and the calcimimetic NPS R-467, a known calcium-sensing receptor (CaSR) agonist, on growth/proliferation of two equine size-sieved umbilical cord matrix mesenchymal stem cell (eUCM-MSC) lines. The involvement of CaSR on observed cell response was analyzed at both the mRNA and protein level.A large (>8 µm in diameter) and a small (<8 µm) cell line were cultured in medium containing: 1) low [Ca(2+)](o) (0.37 mM); 2) high [Ca(2+)](o) (2.87 mM); 3) NPS R-467 (3 µM) in presence of high [Ca(2+)](o) and 4) the CaSR antagonist NPS 2390 (10 µM for 30 min.) followed by incubation in presence of NPS R-467 in medium with high [Ca(2+)](o). Growth/proliferation rates were compared between groups. In large cells, the addition of NPS R-467 significantly increased cell growth whereas increasing [Ca(2+)](o) was not effective in this cell line. In small cells, both higher [Ca(2+)](o) and NPS R-467 increased cell growth. In both cell lines, preincubation with the CaSR antagonist NPS 2390 significantly inhibited the agonistic effect of NPS R-467. In both cell lines, increased [Ca(2+)](o) and/or NPS R-467 reduced doubling time values.Treatment with NPS R-467 down-regulated CaSR mRNA expression in both cell lines. In large cells, NPS R-467 reduced CaSR labeling in the cytosol and increased it at cortical level.In conclusion, calcium and the calcimimetic NPS R-467 reduce CaSR mRNA expression and stimulate cell growth/proliferation in eUCM-MSC. Their use as components of media for eUCM-MSC culture could be beneficial to obtain enough cells for down-stream purposes

    Measurement of B_{s}^{0} meson production in pp and PbPb collisions at \sqrt{SNN}

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    The production cross sections of B_{s}^{0} mesons and charge conjugates are measured in proton-proton (pp) and PbPb collisions via the exclusive decay channel B_{s}^{0}→J/ψϕ→μ^{+}μ^{−}K^{+}K^{−} at a center-of-mass energy of 5.02 TeV per nucleon pair and within the rapidity range |y|<2.4 using the CMS detector at the LHC. The pp measurement is performed as a function of transverse momentum (p_{T}) of the B_{s}^{0} mesons in the range of 7 to 50 GeV/c and is compared to the predictions of perturbative QCD calculations. The B_{s}^{0} production yield in PbPb collisions is measured in two p_{T} intervals, 7 to 15 and 15 to 50 GeV/c, and compared to the yield in pp collisions in the same kinematic region. The nuclear modification factor (R_{AA}) is found to be 1.5±0.6(stat)±0.5(syst) for 7–15 GeV/c, and 0.87±0.30(stat)±0.17(syst) for 15–50 GeV/c, respectively. Within current uncertainties, the B_{s}^{0} results are consistent with models of strangeness enhancement, and suppression by parton energy loss, as observed for the B+ mesons

    Measurement of the tt¯ production cross section, the top quark mass, and the strong coupling constant using dilepton events in pp collisions at √s = 13 TeV

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    A measurement of the top quark–antiquark pair production cross section σtt¯ in proton–proton collisions at a centre-of-mass energy of 13TeV is presented. The data correspond to an integrated luminosity of 35.9fb−1, recorded by the CMS experiment at the CERN LHC in 2016. Dilepton events (e ± μ ∓, μ+μ−, e+e−) are selected and the cross section is measured from a likelihood fit. For a top quark mass parameter in the simulation of mMCt=172.5GeV the fit yields a measured cross section σtt¯=803±2(stat)±25(syst)±20(lumi)pb, in agreement with the expectation from the standard model calculation at next-to-next-to-leading order. A simultaneous fit of the cross section and the top quark mass parameter in the POWHEG simulation is performed. The measured value of mMCt=172.33±0.14(stat)+0.66−0.72(syst)GeV is in good agreement with previous measurements. The resulting cross section is used, together with the theoretical prediction, to determine the top quark mass and to extract a value of the strong coupling constant with different sets of parton distribution functions

    Search for contact interactions and large extra dimensions in the dilepton mass spectra from proton-proton collisions at \sqrt{s} = 13 TeV

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    A search for nonresonant excesses in the invariant mass spectra of electron and muon pairs is presented. The analysis is based on data from proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment in 2016, corresponding to a total integrated luminosity of 36 fb^{-1}. No significant deviation from the standard model is observed. Limits are set at 95% confidence level on energy scales for two general classes of nonresonant models. For a class of fermion contact interaction models, lower limits ranging from 20 to 32 TeV are set on the characteristic compositeness scale Λ. For the Arkani-Hamed, Dimopoulos, and Dvali model of large extra dimensions, the first results in the dilepton final state at 13 TeV are reported, and values of the ultraviolet cutoff parameter Λ_{T} below 6.9 TeV are excluded. A combination with recent CMS diphoton results improves this exclusion to Λ_{T} below 7.7 TeV, providing the most sensitive limits to date in nonhadronic final states

    Measurement of the WZ production cross section in pp collisions at root s=13 Tev

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    Peer reviewe

    Relative Modification of Prompt psi(2S) and J/psi Yields from pp to PbPb Collisions at root(S)(NN)=5.02 TeV

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    Peer reviewe

    Search for the production of W^{\pm} W^{\pm} W^{\mp} events at \sqrt{s} = 13 TeV

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    A search for the production of events containing three W bosons predicted by the standard model is reported. The search is based on a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the CMS experiment at the CERN LHC and corresponding to a total integrated luminosity of 35.9 fb^{-1}. The search is performed in final states with three leptons (electrons or muons), or with two same-charge leptons plus two jets. The observed (expected) significance of the signal for W^{\pm} W^{\pm} W^{\mp} production is 0.60 (1.78) standard deviations, and the ratio of the measured signal yield to that expected from the standard model is 0.34_{-0.34}^{+0.62}. Limits are placed on three anomalous quartic gauge couplings and on the production of massive axionlike particles
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