Eluate derived by extracorporal antibody-based immunoadsorption elevates the cytosolic Ca2+ concentration in podocytes via B-2 kinin receptors

Background/Aim: Patients with idiopathic focal segmental glomerulosclerosis (FSGS) often develop a recurrence of the disease after kidney transplantation. In a number of FSGS patients, plasmapheresis and immunoadsorption procedures have been shown to transiently reduce proteinuria and are thought to do this by eliminating a circulating factor. Direct cellular effects of eluates from immunoadsorption procedures on podocytes, the primary target of injury in FSGS, have not yet been reported. Methods: Eluates were derived from antibody-based immunoadsorption of a patient suffering from primary FSGS, a patient with systemic lupus erythematosus, and a healthy volunteer. The cytosolic free Ca2+ concentration ({[}Ca2+](i)) of differentiated podocytes was measured by single-cell fura-2 microfluorescence measurements. Free and total immunoreactive kinin levels were measured by radioimmunoassay. Results: FSGS eluates increased the {[}Ca2+](i) levels concentration dependently (EC50 0.14 mg/ml; n = 3-19). 1 mg/ml eluate increased the {[}Ca2+](i) values reversibly from 82 +/- 12 to 1,462 +/- 370 nmol/l, and then they returned back to 100 16 nmol/l (n = 19). The eluate-induced increase of {[}Ca2+](i) consisted of an initial Ca2+ peak followed by a Ca2+ plateau which depended on the extracellular Ca2+ concentration. The eluate-induced increase of {[}Ca2+](i) was inhibited by the specific B-2 kinin receptor antagonist Hoe 140 in a concentration-dependent manner (IC50 2.47 nmol/l). In addition, prior repetitive application of bradykinin desensitized the effect of eluate on {[}Ca2+](i). A colonic epithelial cell line not reacting to bradykinin did not respond to eluate either (n = 6). Similar to FSGS eluates, the eluate preparations of both the systemic lupus patient and the healthy volunteer led to a biphasic, concentration-dependent {[}Ca2+](i) increase in poclocytes which again was inhibited by Hoe 140. Free kinins were detected in all eluate preparations. Conclusion: The procedure of antibody-based immunoadsorption leads to kinin in the eluate which elevates the {[}Ca2+](i) level of podocytes via B-2 kinin receptors. Copyright (C) 2002 S. Karger AG, Basel

A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25  ml/min per 1.73  m(2), and a urine protein to creatinine ratio over 1.8  mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4  mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73  m(2)). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2  mg/mg with all three Black patients having a mean decline of 3.6  mg/mg. The half-life of fresolimumab was ∼14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary

Measurement of proton electromagnetic form factors in e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ is measured for the first time. We reach unprecedented accuracy, and precision results in the time-like region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on non-perturbative Quantum Chromodynamics

Observation of ηc→ωω\eta_c\to\omega\omega in J/ψ→γωωJ/\psi\to\gamma\omega\omega

Using a sample of $(1310.6\pm7.0)\times10^6$ $J/\psi$ events recorded with the BESIII detector at the symmetric electron positron collider BEPCII, we report the observation of the decay of the $(1^1 S_0)$ charmonium state $\eta_c$ into a pair of $\omega$ mesons in the process $J/\psi\to\gamma\omega\omega$. The branching fraction is measured for the first time to be $\mathcal{B}(\eta_c\to\omega\omega)= (2.88\pm0.10\pm0.46\pm0.68)\times10^{-3}$, where the first uncertainty is statistical, the second systematic and the third is from the uncertainty of $\mathcal{B}(J/\psi\to\gamma\eta_c)$. The mass and width of the $\eta_c$ are determined as $M=(2985.9\pm0.7\pm2.1)\,$MeV/$c^2$ and $\Gamma=(33.8\pm1.6\pm4.1)\,$MeV.Comment: 13 pages, 6 figure

Observation of the WW-Annihilation Decay Ds+→ωπ+D^{+}_{s} \rightarrow \omega \pi^{+} and Evidence for Ds+→ωK+D^{+}_{s} \rightarrow \omega K^{+}

We report on the observation of the $W$-annihilation decay $D^{+}_{s} \rightarrow \omega \pi^{+}$ and the evidence for $D_{s}^{+} \rightarrow \omega K^{+}$ with a data sample corresponding to an integrated luminosity of 3.19 fb$^{-1}$ collected with the BESIII detector at the center-of-mass energy $\sqrt{s} = 4.178$ GeV. We obtain the branching fractions $\mathcal{B}(D^{+}_{s} \rightarrow \omega \pi^{+}) = (1.77\pm0.32_{{\rm stat.}}\pm0.11_{{\rm sys.}}) \times 10^{-3}$ and $\mathcal{B}(D^{+}_{s} \rightarrow \omega K^{+}) = (0.87\pm0.24_{{\rm stat.}}\pm0.07_{{\rm sys.}}) \times 10^{-3}$, respectively

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Measurements of Weak Decay Asymmetries of Λc+→pKS0\Lambda_c^+\to pK_S^0, Λπ+\Lambda\pi^+, Σ+π0\Sigma^+\pi^0, and Σ0π+\Sigma^0\pi^+

Using $e^+e^-\to\Lambda_c^+\bar\Lambda_c^-$ production from a 567 pb$^{-1}$ data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of $\Lambda_c^+\to pK_S^0$, $\Lambda \pi^+$, $\Sigma^+\pi^0$, and $\Sigma^0\pi^+$. For the first time, the $\Lambda_c^+$ transverse polarization is studied in unpolarized $e^+e^-$ collisions, where a non-zero effect is observed with a statistical significance of 2.1$\sigma$. The decay asymmetry parameters of the $\Lambda_c^+$ weak hadronic decays into $pK_S^0$, $\Lambda\pi^+$, $\Sigma^+\pi^0$ and $\Sigma^0\pi^+$ are measured to be $0.18\pm0.43(\rm{stat})\pm0.14(\rm{syst})$, $-0.80\pm0.11(\rm{stat})\pm0.02(\rm{syst})$, $-0.57\pm0.10(\rm{stat})\pm0.07(\rm{syst})$, and $-0.73\pm0.17(\rm{stat})\pm0.07(\rm{syst})$, respectively. In comparison with previous results, the measurements for the $\Lambda\pi^+$ and $\Sigma^+\pi^0$ modes are consistent but with improved precision, while the parameters for the $pK_S^0$ and $\Sigma^0\pi^+$ modes are measured for the first time

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Evidence for the decays of Λc+→Σ+η\Lambda^+_{c}\to\Sigma^+\eta and Σ+η′\Sigma^+\eta^\prime

We study the hadronic decays of $\Lambda_{c}^{+}$ to the final states $\Sigma^{+}\eta$ and $\Sigma^+\eta^\prime$, using an $e^{+}e^{-}$ annihilation data sample of 567 pb$^{-1}$ taken at a center-of-mass energy of 4.6 GeV with the BESIII detector at the BEPCII collider. We find evidence for the decays $\Lambda_{c}^{+}\rightarrow\Sigma^{+}\eta$ and $\Sigma^+\eta^\prime$ with statistical significance of $2.5\sigma$ and $3.2\sigma$, respectively. Normalizing to the reference decays $\Lambda_c^+\to\Sigma^+\pi^0$ and $\Sigma^+\omega$, we obtain the ratios of the branching fractions $\frac{{\mathcal B}(\Lambda_c^+\to\Sigma^+\eta)}{{\mathcal B}(\Lambda_c^+\to\Sigma^+\pi^0)}$ and $\frac{{\mathcal B}(\Lambda_c^+\to\Sigma^+\eta^\prime)}{{\mathcal B}(\Lambda_c^+\to\Sigma^+\omega)}$ to be $0.35 \pm 0.16 \pm 0.03$ and $0.86 \pm 0.34 \pm 0.07$, respectively. The upper limits at the 90\% confidence level are set to be $\frac{{\mathcal B}(\Lambda_c^+\to\Sigma^+\eta)}{{\mathcal B}(\Lambda_c^+\to\Sigma^+\pi^0)}<0.58$ and $\frac{{\mathcal B}(\Lambda_c^+\to\Sigma^+\eta^\prime)}{{\mathcal B}(\Lambda_c^+\to\Sigma^+\omega)}<1.2$. Using BESIII measurements of the branching fractions of the reference decays, we determine $\mathcal B({\Lambda_{c}^{+}\rightarrow\Sigma^{+}\eta})=(0.41\pm0.19\pm0.05)\%$ ($<0.68\%$) and $\mathcal B({\Lambda_{c}^{+}\rightarrow\Sigma^{+}\eta'})=(1.34\pm0.53\pm0.21)\%$ ($<1.9\%$). Here, the first uncertainties are statistical and the second systematic. The obtained branching fraction of $\Lambda_c^+\to\Sigma^+\eta$ is consistent with the previous measurement, and the branching fraction of $\Lambda_{c}^{+}\rightarrow\Sigma^{+}\eta^{\prime}$ is measured for the first time.Comment: Accepted by Chin. Phys. C : Chin. Phys. C 43, 083002, (2019