Faculty Bibliography

The understanding of marine microbial ecology and metabolism has been hampered by the paucity of sequenced reference genomes. To this end, we report the sequencing of 137 diverse marine isolates collected from around the world. We analysed these sequences, along with previously published marine prokaryotic genomes, in the context of marine metagenomic data, to gain insights into the ecology of the surface ocean prokaryotic picoplankton (0.1-3.0 μm size range). The results suggest that the sequenced genomes define two microbial groups: one composed of only a few taxa that are nearly always abundant in picoplanktonic communities, and the other consisting of many microbial taxa that are rarely abundant. The genomic content of the second group suggests that these microbes are capable of slow growth and survival in energy-limited environments, and rapid growth in energy-rich environments. By contrast, the abundant and cosmopolitan picoplanktonic prokaryotes for which there is genomic representation have smaller genomes, are probably capable of only slow growth and seem to be relatively unable to sense or rapidly acclimate to energy-rich conditions. Their genomic features also lead us to propose that one method used to avoid predation by viruses and/or bacterivores is by means of slow growth and the maintenance of low biomass.

UNet(SM) , the UNOS data collection and electronic organ allocation system, allows centers to specify organ offer acceptance criteria for patients on their kidney waiting list. We hypothesized that the system might not be fully utilized and that the criteria specified by most transplant centers would be much broader than the characteristics of organs actually transplanted by those centers. We analyzed the distribution of criteria values among waitlist patients (N = 304 385) between January 2000 and February 2009, mean criteria values among listed candidates on February 19, 2009 and differences between a center's specified criteria and the organs it accepted for transplant between July 2005 and April 2009. We found wide variation in use of criteria variables, with some variables mostly or entirely unused. Most centers specified very broad criteria, with little within-center variation by patient. An offer of a kidney with parameters more extreme than the maximum actually transplanted at that center was designated a 'surplus offer' and indicated a potentially avoidable delay in distribution. We found 7373 surplus offers (7.1% of all offers), concentrated among a small number of centers. The organ acceptance criteria system is currently underutilized, leading to possibly avoidable inefficiencies in organ distribution.

INTRODUCTION: Delayed graft function (DGF) and slow graft function (SGF) due to ischemic and reperfusion injury (IRI) are common complications of deceased donor kidney transplantation. We tested whether a panel of serum and urine cytokines represent early biomarkers for DGF and SGF. METHODS: We collected serum and urine samples from 61 patients 48 hours posttransplantation and used a multiplex enzyme-linked immunosorbent assay (ELISA) technique to measure levels of 23 cytokines. Fourteen patients developed poor graft function (PGF), with 6 having DGF and 8 with SGF. RESULTS: Area under receiver operation characteristics curve (AUC) demonstrated the following: serum levels of SCF (0.88) and interleukin (IL) 16 (0.74). CONCLUSIONS: This study showed that a select panel of cytokines measured early post kidney transplantation may predict poor graft function.

OBJECTIVE: No therapy except liver transplantation currently exists for patients with acute liver failure (ALF). The aim of this study was to determine whether pharmacologic mobilization of endogenous hematopoietic stem cells (HSCs) can aid in liver repair and improve survival in an animal model of ALF. METHODS: Rodents were treated with a single near-lethal intraperitoneal injection of carbon tetrachloride (CCl4). After 12 hours, animals were randomized to receive plerixafor and granulocyte colony-stimulating factor (G-CSF), agents known to mobilize marrow-derived stem cells, or saline vehicle injection. Mice were observed for survival, and serial assessment of liver injury by serum transaminase measurements, and histologic analysis was performed. RESULTS: In our ALF model, 7-day survival after injection of CCl4 was 25%. Administration of plerixafor and G-CSF following CCl4 resulted in 87% survival (n = 8, P < 0.05). On serial histopathologic analysis, animals treated with plerixafor and G-CSF demonstrated less hepatic injury compared with control animals. Evaluation of peripheral blood demonstrated an increase in circulating HSCs in response to plerixafor and G-CSF, and immunostaining suggested the infiltration of HSCs into the hepatic parenchyma after stem cell mobilization. CONCLUSIONS: Our results suggest a possible new treatment strategy for patients with ALF, a group for whom either liver transplantation or death is frequently the outcome. Pharmacologic agents that mobilize HSCs may lead to an infiltration of the injured liver with cells that may participate in or expedite liver regeneration. This therapy has the potential to avert liver transplantation in some patients with ALF and may be of benefit in a wide variety of medical and surgical patients with liver injury.