Surveillance biopsies in children post-kidney transplant

Surveillance biopsies are increasingly used in the post-transplant monitoring of pediatric renal allograft recipients. The main justification for this procedure is to diagnose early and presumably modifiable acute and chronic renal allograft injury. Pediatric recipients are theoretically at increased risk for subclinical renal allograft injury due to their relatively large adult-sized kidneys and their higher degree of immunological responsiveness. The safety profile of this procedure has been well investigated. Patient morbidity is low, with macroscopic hematuria being the most common adverse event. No patient deaths have been attributed to this procedure. Longitudinal surveillance biopsy studies have revealed a substantial burden of subclinical immunological and non-immunological injury, including acute cellular rejection, interstitial fibrosis and tubular atrophy, microvascular lesions and transplant glomerulopathy. The main impediment to the implementation of surveillance biopsies as the standard of care is the lack of demonstrable benefit of early histological detection on long-term outcome. The considerable debate surrounding this issue highlights the need for multicenter, prospective, and randomized studies

On Planetary Companions to the MACHO-98-BLG-35 Microlens Star

We present observations of microlensing event MACHO-98-BLG-35 which reached a peak magnification factor of almost 80. These observations by the Microlensing Planet Search (MPS) and the MOA Collaborations place strong constraints on the possible planetary system of the lens star and show intriguing evidence for a low mass planet with a mass fraction $4\times 10^{-5} \leq \epsilon \leq 2\times 10^{-4}$. A giant planet with $\epsilon = 10^{-3}$ is excluded from 95% of the region between 0.4 and 2.5 $R_E$ from the lens star, where $R_E$ is the Einstein ring radius of the lens. This exclusion region is more extensive than the generic "lensing zone" which is $0.6 - 1.6 R_E$. For smaller mass planets, we can exclude 57% of the "lensing zone" for $\epsilon = 10^{-4}$ and 14% of the lensing zone for $\epsilon = 10^{-5}$. The mass fraction $\epsilon = 10^{-5}$ corresponds to an Earth mass planet for a lensing star of mass \sim 0.3 \msun. A number of similar events will provide statistically significant constraints on the prevalence of Earth mass planets. In order to put our limits in more familiar terms, we have compared our results to those expected for a Solar System clone averaging over possible lens system distances and orientations. We find that such a system is ruled out at the 90% confidence level. A copy of the Solar System with Jupiter replaced by a second Saturn mass planet can be ruled out at 70% confidence. Our low mass planetary signal (few Earth masses to Neptune mass) is significant at the $4.5\sigma$ confidence level. If this planetary interpretation is correct, the MACHO-98-BLG-35 lens system constitutes the first detection of a low mass planet orbiting an ordinary star without gas giant planets.Comment: ApJ, April 1, 2000; 27 pages including 8 color postscript figure

Study of variable stars in the MOA data base: long-period red variables in the Large Magellanic Cloud

One hundred and forty six long-period red variable stars in the Large Magellanic Cloud (LMC) from the three year MOA project database were analysed. A careful periodic analysis was performed on these stars and a catalogue of their magnitudes, colours, periods and amplitudes is presented. We convert our blue and red magnitudes to $K$ band values using 19 oxygen-rich stars. A group of red short-period stars separated from the Mira sequence has been found on a (log P, K) diagram. They are located at the short period side of the Mira sequence consistent with the work of Wood and Sebo (1996). There are two interpretations for such stars; a difference in pulsation mode or a difference in chemical composition. We investigated the properties of these stars together with their colour, amplitude and periodicity. We conclude that they have small amplitudes and less regular variability. They are likely to be higher mode pulsators. A large scatter has been also found on the long period side of the (log P, K) diagram. This is possibly a systematic spread given that the blue band of our photometric system covers both standard B and V bands and affects carbon-rich stars.Comment: 19 pages, 19 figures, accepted for publication in MNRA

N-Octanoyl-Dopamine inhibits cytokine production in activated T-cells and diminishes MHC-class-II expression as well as adhesion molecules in IFN gamma-stimulated endothelial cells

IFN gamma enhances allograft immunogenicity and facilitates T-cell mediated rejection. This may cause interstitial fibrosis and tubular atrophy (IFTA), contributing to chronic allograft loss. We assessed if inhibition of T-cell activation by N-octanoyl dopamine (NOD) impairs adherence of activated T-cells to endothelial cells and the ability of activated T-cells to produce IFN gamma. We also assessed if NOD affects IFN gamma mediated gene expression in endothelial cells. The presence of NOD during T-cell activation significantly blunted their adhesion to unstimulated and cytokine stimulated HUVEC. Supernatants of these T-cells displayed significantly lower concentrations of TNF alpha and IFN gamma and were less capable to facilitate T-cell adhesion. In the presence of NOD VLA-4 (CD49d/CD29) and LFA-1 (CD11a/CD18) expression on T-cells was reduced. NOD treatment of IFN gamma stimulated HUVEC reduced the expression of MHC class II transactivator (CIITA), of MHC class II and its associated invariant chain CD74. Since IFTA is associated with T-cell mediated rejection and IFN gamma to a large extent regulates immunogenicity of allografts, our current data suggest a potential clinical use of NOD in the treatment of transplant recipients. Further in vivo studies are warranted to confirm these in vitro findings and to assess the benefit of NOD on IFTA in clinically relevant models

Metabolic stress promotes renal tubular inflammation by triggering the unfolded protein response

The renal epithelium contributes to the development of inflammation during ischemic injury. Ischemia induces endoplasmic reticulum (ER) stress and activates the unfolded protein response (UPR). Ischemic tissues generate distress signals and inflammation that activates fibrogenesis and may promote adaptive immunity. Interestingly, the UPR may activate inflammation pathways. Our aim was to test whether the UPR is activated during metabolic stress and mediates a tubular inflammatory response. Glucose deprivation, not hypoxia and amino acids deprivation, activated the UPR in human renal cortical tubular cells in culture. This stress activated NF-κB and promoted the transcription of proinflammatory cytokines and chemokines, including IL-6, IL-8, TNF-α, RANTES and MCP-1. The protein kinase RNA (PKR)-like ER kinase signaling pathway was not required for the induction of inflammation but amplified cytokine. Inositol-requiring enzyme 1 activated NF-κB signaling and was required for the transcription of proinflammatory cytokines and chemokines following metabolic stress. Moreover, acute ischemia activated ER stress and inflammation in rat kidneys. Finally, the ER stress marker GRP78 and NF-κB p65/RelA were coexpressed in human kidney transplants biopsies performed before implantation, suggesting that ER stress activates tubular inflammation in human renal allografts. In conclusion, this study establishes a link between ischemic stress, the activation of the UPR and the generation of a tubular inflammatory response

Study by MOA of extra-solar planets in gravitational microlensing events of high magnification

A search for extra-solar planets was carried out in three gravitational microlensing events of high magnification, MACHO 98-BLG-35, MACHO 99-LMC-2, and OGLE 00-BUL-12. Photometry was derived from observational images by the MOA and OGLE groups using an image subtraction technique. For MACHO 98-BLG-35, additional photometry derived from the MPS and PLANET groups was included. Planetary modeling of the three events was carried out in a super-cluster computing environment. The estimated probability for explaining the data on MACHO 98-BLG-35 without a planet is <1%. The best planetary model has a planet of mass ~(0.4-1.5) X 10^-5 M_Earth at a projected radius of either ~1.5 or ~2.3 AU. We show how multi-planet models can be applied to the data. We calculated exclusion regions for the three events and found that Jupiter-mass planets can be excluded with projected radii from as wide as about 30 AU to as close as around 0.5 AU for MACHO 98-BLG-35 and OGLE 00-BUL-12. For MACHO 99-LMC-2, the exclusion region extends out to around 10 AU and constitutes the first limit placed on a planetary companion to an extragalactic star. We derive a particularly high peak magnification of ~160 for OGLE 00-BUL-12. We discuss the detectability of planets with masses as low as Mercury in this and similar events.Comment: 14 pages, 16 embedded postscript figures, 3 PNG figures, revised version accepted by MNRA