The changing immunology of organ transplantation

The engrafted organ becomes a chimera as the recipient's leukocytes station themselves in the transplant. Remarkably, the recipient becomes chimeric as well, in a reverse migration involving immune cells from the graft. Interactions between donor and recipient cells are tolerogenic-a process with implications for the goal of graft acceptance with minimal immunosuppression

The dust morphology of the elliptical Galaxy M86 with SPIRE

We present Herschel-SPIRE observations at 250–500 μm of the giant elliptical galaxy M 86 and examine the distribution of the resolved cold dust emission and its relation with other galactic tracers. The SPIRE images reveal three dust components: emission from the central region; a dust lane extending north-south; and a bright emission feature 10 kpc to the south-east. We estimate that ~10^6 M_☉ of dust is spatially coincident with atomic and ionized hydrogen, originating from stripped material from the nearby spiral NGC 4438 due to recent tidal interactions with M 86. The gas-to-dust ratio of the cold gas component ranges from ~20–80. We discuss the different heating mechanisms for the dust features

Microchimerism, dendritic cell progenitors and transplantation tolerance

The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrow‐derived dendritic cell (DC). These cells have been classically perceived as the most potent antigen‐presenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM‐CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T‐dependent areas of host lymphoid tissue, where some at least upregulate cell surface MHC class II. These donor‐derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver. A key finding is that in mice, progeny of these donor‐derived DC progenitors can be propagated ex vivo from the bone marrow and other lymphoid tissues of nonimmunosuppressed spontaneously tolerant liver allograft recipients. In humans, donor DC can also be grown from the blood of organ allograft recipients whose organ‐source chimerism is augmented with donor bone marrow infusion. DC progenitors cannot, however, be propagated from the lymphoid tissue of nonimmunosuppressed cardiac‐allografted mice that reject their grafts. These findings are congruent with the possibility that bidirectional leukocyte migration and donor cell chimerism play key roles in acquired transplantation tolerance. Although the cell interactions are undoubtedly complex, a discrete role can be identified for DC under well‐defined experimental conditions. Bone marrow‐derived DC progenitors (MHC class II+, B7–1dim, B7–2−) induce alloantigen‐specific hyporesponsiveness (anergy) in naive T cells in vitro. Moreover, costimulatory molecule‐deficient DC progenitors administered systemically prolong the survival of mouse heart or pancreatic islet allografts. How the regulation of donor DC phenotype and function relates to the balance between the immunogenicity and tolerogenicity of organ allografts remains to be determined. Copyright © 1995 AlphaMed Pres

Donor hematopoietic progenitor cells in nonmyeloablated rat recipients of allogeneic bone marrow and liver grafts

Background. Although the persistence of multilineage microchimerism in recipients of long-surviving organ transplants implies engraftment of migratory pluripotent donor stem cells, the ultimate localization in the recipient of these cells has not been determined in any species. Methods. Progenitor cells were demonstrated in the bone marrow and nonparenchymal liver cells of naive rats and in Brown Norway (BN) recipients of Lewis (LEW) allografts by semiquantitative colony-forming unit in culture (CFU-C) assays. The LEW allografts of bone marrow cells (BMC) (2.5xl08), orthotopic livers, or heterotopic hearts (abdominal site) were transplanted under a 2-week course of daily tacrolimus, with additional single doses on days 20 and 27. Donor CFU-C colonies were distinguished from recipient colonies in the allografts and recipient bone marrow with a donor-specific MHC class II monoclonal antibody. The proportions of donor and recipient colonies were estimated from a standard curve created by LEW and BN bone marrow mixtures of known concentrations. Results. After the BMC infusions, 5-10% of the CFU-C in the bone marrow of BN recipients were of the LEW phenotype at 14, 30, and 60 days after transplantation. At 100 days, however, donor CFU-C could no longer be found at this site. The pattern of LEW CFU-C in the bone marrow of BN liver recipients up to 60 days was similar to that in recipients of 2.5 x 108 BMC, although the donor colonies were only 1/20 to 1/200 as numerous. This was expected, because the progenitor cells in the passenger leukocytes of a single liver are equivalent to those in 1-5x106 BMC. Using a liquid CFU-C assay, donor progenitor cells were demonstrated among the nonparenchymal cells of liver allografts up to 100 days. In contrast, after heart transplantation, donor CFU-C could not be identified in the recipient bone marrow, even at 14 days. Conclusion. Under effective immunosuppression, allogeneic hematopoietic progenitors compete effectively with host cells for initial engraftment in the bone marrow of noncytoablated recipients, but disappear from this location between 60 and 100 days after transplantation, coincident with the shift of donor leukocyte chimerism from the lymphoid to the nonlymphoid compartment that we previously have observed in this model. It is possible that the syngeneic parenchymal environment of the liver allografts constitutes a privileged site for persistent progenitor donor cells

Thermal Hall Conductivity as a Probe of Gap Structure in Multi-band Superconductors: The Case of Ba1−xKxFe2As2\rm Ba_{1-x}K_xFe_2As_2

The sign and profile of the thermal Hall conductivity $\kappa_{xy}$ gives important insights into the gap structure of multi-band superconductors. With this perspective, we have investigated $\kappa_{xy}$ and the thermal conductivity $\kappa_{xx}$ in $\rm Ba_{1-x}K_xFe_2As_2$ which display large peak anomalies in the superconducting state. The anomalies imply that a large hole-like quasiparticle (qp) population exists below the critical temperature $T_c$. We show that the qp mean-free-path inferred from $\kappa_{xx}$ reproduces the observed anomaly in $\kappa_{xy}$, providing a consistent estimate of a large qp population. Further, we demonstrate that the hole-like signal is consistent with a theoretical scenario where despite potentially large gap variations on the electron pockets, the minimal homogeneous gap of the superconducting phase resides at a hole pocket. Implications for probing the gap structure in the broader class of pnictide superconductors are discussed.Comment: 5 pages, 4 figures. Orientation significantly updated from previous (0811.4668v1) reflecting new theoretical understanding of experimental results and physical implications. Introduction, discussion, and figures updated including additional figure for model calculatio

The prevalence of insomnia in the general population in China: A meta-analysis

This is the first meta-analysis of the pooled prevalence of insomnia in the general population of China. A systematic literature search was conducted via the following databases: PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Interne (CNKI), WanFang Data and SinoMed). Statistical analyses were performed using the Comprehensive Meta-Analysis program. A total of 17 studies with 115,988 participants met the inclusion criteria for the analysis. The pooled prevalence of insomnia in China was 15.0% (95% Confidence interval [CI]: 12.1%-18.5%). No significant difference was found in the prevalence between genders or across time period. The pooled prevalence of insomnia in population with a mean age of 43.7 years and older (11.6%; 95% CI: 7.5%-17.6%) was significantly lower than in those with a mean age younger than 43.7 years (20.4%; 95% CI: 14.2%-28.2%). The prevalence of insomnia was significantly affected by the type of assessment tools (Q = 14.1, P = 0.001). The general population prevalence of insomnia in China is lower than those reported in Western countries but similar to those in Asian countries. Younger Chinese adults appear to suffer from more insomnia than older adults

Radial distribution of gas and dust in spiral galaxies: The case of M 99 (NGC 4254) and M 100 (NGC 4321)

By combining Herschel-SPIRE data with archival Spitzer, H i , and CO maps, we investigate the spatial distribution of gas and dust in the two famous grand-design spirals M 99 and M 100 in the Virgo cluster. Thanks to the unique resolution and sensitivity of the Herschel-SPIRE photometer, we are for the first time able to measure the distribution and extent of cool, submillimetre (submm)-emitting dust inside and beyond the optical radius. We compare this with the radial variation in both the gas mass and the metallicity. Although we adopt a model-independent, phenomenological approach, our analysis provides important insights. We find the dust extending to at least the optical radius of the galaxy and showing breaks in its radial profiles at similar positions as the stellar distribution. The colour indices f350/f500 and f250/f350 decrease radially consistent with the temperature decreasing with radius. We also find evidence of an increasing gas to dust ratio with radius in the outer regions of both galaxies