Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports

Ueno T., Hiwatashi S., Saka R., et al. Everolimus Rescue Treatment for Chronic Rejection After Pediatric Living Donor Liver Transplantation: 2 Case Reports. Transplantation Proceedings 50, 2872 (2018); https://doi.org/10.1016/J.TRANSPROCEED.2018.03.079.Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective. The patient was diagnosed with CR, and everolimus was started with a target trough level of about 5 ng/mL. LFTs improved and pathological examination showed no progression of hepatic fibrosis. Case 2 was a 10-year-old girl with Alagille syndrome who underwent LDLT at 1 year of age. She had biopsy-proven acute cellular rejection with prolonged LFT abnormalities beginning 3 years after transplantation. She was treated with steroid pulse therapy, followed by MMF, tacrolimus, and prednisolone. Her condition did not improve, even after subsequent ATG administration. CR was suspected based on liver biopsy in the fourth postoperative year, and everolimus was introduced. The target trough level was around 5 ng/mL, but was reduced to 3 ng/mL due to stomatitis. Four years have passed since the initiation of everolimus, and LFTs are stable with no progression of liver biopsy fibrosis. We describe 2 cases in which everolimus was administered for CR. In both cases, LFTs improved and fibrosis did not progress, suggesting that everolimus is an effective treatment for CR after LDLT

Pulmonary Arterial Pressure Management Based on Oral Medicine for Pediatric Living Donor Liver Transplant With Portopulmonary Hypertension

Ueno T., Hiwatashi S., Saka R., et al. Pulmonary Arterial Pressure Management Based on Oral Medicine for Pediatric Living Donor Liver Transplant With Portopulmonary Hypertension. Transplantation Proceedings 50, 2614 (2018); https://doi.org/10.1016/J.TRANSPROCEED.2018.03.068.Pediatric living donor liver transplantation (LDLT) in patients with advanced portopulmonary hypertension (PoPH) is associated with poor prognoses. Recently, novel oral medications, including endothelin receptor antagonists (ERAs), phosphodiesterase 5 (PDE5) inhibitors, and oral prostacyclin (PGI2) have been used to treat PoPH. Pediatric patients with PoPH who underwent LDLT from 2006 to 2016 were enrolled. Oral pulmonary hypertension (PH) medication was administered to control pulmonary arterial pressure (PAP). Four patients had PoPH. Their ages ranged from 6 to 16 years, and their original diseases were biliary atresia (n = 2), portal vein obstruction (n = 1), and intrahepatic portal systemic shunt (n = 1). For preoperative management, 2 patients received continuous intravenous PGI2 and 2 oral medications (an ERA alone or an ERA and a PDE5 inhibitor), and 2 received only oral drugs (an ERA and a PDE5 inhibitor). One patient managed only with intravenous PGI2 died. In the remaining 3 cases, intravenous PGI2 or NO was discontinued before the end of the first postoperative week. Postoperative medications were oral PGI2 alone (n = 1), an ERA alone (n = 1), or the combination of an ERA and a PDE5 inhibitor (n = 1). An ERA was the first-line therapy, and a PDE5 inhibitor was added if there was no effect. New oral PH medications were effective and safe for use in pediatric patients following LDLT. In particular, these new oral drugs prevent the need for central catheter access to infuse PGI2

Magnetic structures of RbCuCl_3 in a transverse field

A recent high-field magnetization experiment found a phase transition of unknown character in the layered, frustrated antiferromagnet RbCuCl_3, in a transverse field (in the layers). Motivated by these results, we have examined the magnetic structures predicted by a model of RbCuCl_3, using the classical approximation. At small fields, we obtain the structure already known to be optimal, an incommensurate (IC) spiral with wave vector q in the layers. At higher fields, we find a staircase of long-period commensurate (C) phases (separated initially by the low-field IC phase), then two narrow IC phases, then a fourth IC phase (also with intermediate C phases), and finally the ferromagnetically aligned phase at the saturation field H_S. The three-sublattice C states familiar from the theory of the triangular antiferromagnet are never optimal. The C phases and the two intermediate IC phases were previously unknown in this context. The magnetization is discontinuous at a field \approx 0.4H_S, in qualitative agreement with experiment, though we find much fine structure not reported.Comment: 9 pages, 8 figure

Electronic structure of Co_xTiSe_2 and Cr_xTiSe_2

The results of investigations of intercalated compounds Cr_xTiSe_2 and Co_xTiSe_2 by X-ray photoelectron spectroscopy (XPS) and X-ray emission spectroscopy (XES) are presented. The data obtained are compared with theoretical results of spin-polarized band structure calculations. A good agreement between theoretical and experimental data for the electronic structure of the investigated materials has been observed. The interplay between the M3d--Ti3d hybridization (M=Cr, Co) and the magnetic moment at the M site is discussed. A 0.9 eV large splitting of the core Cr2p{3/2} level was observed, which reveals a strong exchange magnetic interaction of 3d-2p electrons of Cr. In the case of a strong localization of the Cr3d electrons (for x<0.25), the broadening of the CrL spectra into the region of the states above the nominal Fermi level was observed and attributed to X-ray re-emission. The measured kinetic properties are in good accordance with spectral investigations and band calculation results.Comment: 14 pages, 11 figures, submitted to Phys.Rev.

Oblique triangular antiferromagnetic phase in CsCu1−x_{1-x}Cox_xCl3_3

The spin-1/2 stacked triangular antiferromagnet CsCu$_{1-x}$Co$_x$Cl$_3$ with $0.015<x<0.032$ undergoes two phase transitions at zero field. The low-temperature phase is produced by the small amount of Co$^{2+}$ doping. In order to investigate the magnetic structures of the two ordered phases, the neutron elastic scattering experiments have been carried out for the sample with $x\approx 0.03$. It is found that the intermediate phase is identical to the ordered phase of CsCuCl$_3$, and that the low-temperature phase is an oblique triangular antiferromagnetic phase in which the spins form a triangular structure in a plane tilted from the basal plane. The tilting angle which is 42$^{\circ}$ at $T=1.6$ K decreases with increasing temperature, and becomes zero at $T_{\rm N2} =7.2$ K. An off-diagonal exchange term is proposed as the origin of the oblique phase.Comment: 6 pages, 7 figure

Fluctuation-induced phase in CsCuCl3 in transverse magnetic field: Theory

CsCuCl3 is a quantum triangular antiferromagnet, ferromagnetically stacked, with an incommensurate (IC) structure due to a Dzyaloshinskii-Moriya interaction. Because of the classical degeneracy caused by the frustration, fluctuations in CsCuCl3 have extraordinarily large effects, such as the phase transition in longitudinal magnetic field (normal to the planes, parallel to the IC wavenumber q) and the plateau in q in transverse field (perpendicular to q). We argue that fluctuations are responsible also for the new IC phase discovered in transverse field near the Neel temperature T_N, by T. Werner et al. [Solid State Commun. 102, p.609 (1997)]. We develop and analyse the corresponding minimal Landau theory; the effects of fluctuations on the frustration are included phenomenologically, by means of a biquadratic term. The Landau theory gives two IC phases, one familiar from previous studies; properties of the new IC phase, which occupies a pocket of the temperature-field phase diagram near T_N, agree qualitatively with those of the new phase found experimentally.Comment: 12 pages, revtex, 4 postscript figures, submitted to J. Phys: Condens. Matte

Transcription Regulation of Sex-Biased Genes during Ontogeny in the Malaria Vector Anopheles gambiae

In Anopheles gambiae, sex-regulated genes are responsible for controlling gender dimorphism and are therefore crucial in determining the ability of female mosquitoes to transmit human malaria. The identification and functional characterization of these genes will shed light on the sexual development and maturation of mosquitoes and provide useful targets for genetic control measures aimed at reducing mosquito fertility and/or distorting the sex ratio

Dynein light chain 1 functions in somatic cyst cells regulate spermatogonial divisions in Drosophila

Stem cell progeny often undergo transit amplifying divisions before differentiation. In Drosophila, a spermatogonial precursor divides four times within an enclosure formed by two somatic-origin cyst cells, before differentiating into spermatocytes. Although germline and cyst cell-intrinsic factors are known to regulate these divisions, the mechanistic details are unclear. Here, we show that loss of dynein-light-chain-1 (DDLC1/LC8) in the cyst cells eliminates bag-of-marbles (bam) expression in spermatogonia, causing gonial cell hyperplasia in Drosophila testis. The phenotype is dominantly enhanced by Dhc64C (cytoplasmic Dynein) and didum (Myosin V) loss-of-function alleles. Loss of DDLC1 or Myosin V in the cyst cells also affects their differentiation. Furthermore, cyst cell-specific loss of ddlc1 disrupts Armadillo, DE-cadherin and Integrin-βPS localizations in the cyst. Together, these results suggest that Dynein and Myosin V activities, and independent DDLC1 functions in the cyst cells organize the somatic microenvironment that regulates spermatogonial proliferation and differentiation

Infectious Speciation Revisited: Impact of Symbiont-Depletion on Female Fitness and Mating Behavior of Drosophila paulistorum

The neotropical Drosophila paulistorum superspecies, consisting of at least six geographically overlapping but reproductively isolated semispecies, has been the object of extensive research since at least 1955, when it was initially trapped mid-evolution in flagrant statu nascendi. In this classic system females express strong premating isolation patterns against mates belonging to any other semispecies, and yet uncharacterized microbial reproductive tract symbionts were described triggering hybrid inviability and male sterility. Based on theoretical models and limited experimental data, prime candidates fostering symbiont-driven speciation in arthropods are intracellular bacteria belonging to the genus Wolbachia. They are maternally inherited symbionts of many arthropods capable of manipulating host reproductive biology for their own benefits. However, it is an ongoing debate as to whether or not reproductive symbionts are capable of driving host speciation in nature and if so, to what extent. Here we have reevaluated this classic case of infectious speciation by means of present day molecular approaches and artificial symbiont depletion experiments. We have isolated the α-proteobacteria Wolbachia as the maternally transmitted core endosymbionts of all D. paulistorum semispecies that have coevolved towards obligate mutualism with their respective native hosts. In hybrids, however, these mutualists transform into pathogens by overreplication causing embryonic inviability and male sterility. We show that experimental reduction in native Wolbachia titer causes alterations in sex ratio, fecundity, and mate discrimination. Our results indicate that formerly designated Mycoplasma-like organisms are most likely Wolbachia that have evolved by becoming essential mutualistic symbionts in their respective natural hosts; they have the potential to trigger pre- and postmating isolation. Furthermore, in light of our new findings, we revisit the concept of infectious speciation and discuss potential mechanisms that can restrict or promote symbiont-induced speciation at post- and prezygotic levels in nature and under artificial laboratory conditions

Rates of fixation by lightning of carbon and nitrogen in possible primitive atmospheres

A thermochemical-hydrodynamic model of the production of trace species by electrical discharges has been used to estimate the rates of fixation of C and N by lightning in the primitive atmosphere. Calculations for various possible mixtures of CH 4 , CO 2 , N 2 , H 2 , and H 2 O reveal that the prime species produced were probably HCN and NO and that the key parameter determining the rates of fixation was the ratio of C atoms to O atoms in the atmosphere. Atmospheres with C more abundant than O have large HCN fixation rates, in excess of 10 17 molecules J −1 , but small NO yields. However, when O is more abundant than C, the NO fixation rate approaches 10 17 molecules J −1 while the HCN yield is small. The implications for the evolution of life are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43346/1/11084_2004_Article_BF00931483.pd