Journal ArticlePediatr Transplant · December 2024
BACKGROUND: Natural killer (NK) cells have gained recognition for playing an integral role in both alloimmunity and protective immunity, particularly viral infection control, in solid organ transplantation. Using data from the Clinical Trials in Organ Tran ...
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Journal ArticleAnn Surg · November 1, 2024
OBJECTIVE: To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies. BACKGROUND: Surgeons who conduct research in addition to patient care are refer ...
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Journal ArticleJ Immunol · November 1, 2024
Alemtuzumab induction with belatacept/rapamycin-based maintenance immunotherapy (ABR) prevents kidney allograft rejection and specifically limits early costimulation blockade-resistant rejection (CoBRR). To evaluate the mechanisms by which this regimen alt ...
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Journal ArticleAm J Transplant · October 18, 2024
Endothelial cells (ECs) are an initial barrier between vascularized organ allografts and the host immune system and are thus well positioned to initiate and influence alloimmune rejection. The mammalian target of rapamycin inhibitor rapamycin is known to i ...
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Journal ArticleAm J Transplant · August 2024
Mouse models have been instrumental in understanding mechanisms of transplant rejection and tolerance, but cross-study reproducibility and translation of experimental findings into effective clinical therapies are issues of concern. The Mouse Models in Tra ...
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Journal ArticleAnn Surg · December 1, 2023
OBJECTIVES: To characterize and quantify accumulating immunologic alterations, pre and postoperatively in patients undergoing elective surgical procedures. BACKGROUND: Elective surgery is an anticipatable, controlled human injury. Although the human respon ...
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Journal ArticleAnn Surg · December 1, 2023
OBJECTIVE: To implement a machine learning model using only the restricted data available at case creation time to predict surgical case length for multiple services at different locations. BACKGROUND: The operating room is one of the most expensive resour ...
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Journal ArticleAnn Surg Open · December 2023
OBJECTIVE: This study aims to introduce key concepts and methods that inform the design of studies that seek to quantify the causal effect of social determinants of health (SDOH) on access to and outcomes following organ transplant. BACKGROUND: The causal ...
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Journal ArticleAm J Transplant · September 2023
In June 2022, the US Food and Drug Administration Center for Biologics Evaluation and Research held the 73rd meeting of the Cellular, Tissue, and Gene Therapies Advisory Committee for public discussion of regulatory expectations for xenotransplantation pro ...
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Journal ArticleSci Transl Med · August 30, 2023
Prior studies of anti-CD40 ligand (CD40L)-based immunosuppression demonstrated effective prevention of islet and kidney allograft rejection in nonhuman primate models; however, clinical development was halted because of thromboembolic complications. An ant ...
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Journal ArticleAm J Transplant · July 2023
Porcine vascular endothelial cells (PECs) form a mechanistic centerpiece of xenograft rejection. Here, we determined that resting PECs release swine leukocyte antigen class I (SLA-I) but not swine leukocyte antigen class-II DR (SLA-DR) expressing extracell ...
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Journal ArticleJ Trauma Acute Care Surg · July 1, 2023
BACKGROUND: Thoracic injury can cause impairment of lung function leading to respiratory complications such as pneumonia (PNA). There is increasing evidence that central memory T cells of the adaptive immune system play a key role in pulmonary immunity. We ...
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Journal ArticleAm J Transplant · March 2023
The choice of deprivation index can influence conclusions drawn regarding the extent of deprivation within a community and the identification of the most deprived communities in the United States. This study aimed to determine the degree of correlation amo ...
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Journal ArticleClin Transplant · March 2023
Dr John S Najarian (1927-2020), chairman of the Department of Surgery at the University of Minnesota from 1967 to 1993, was a pioneer in surgery, clinical immunology and transplantation. A Covid-delayed Festschrift was held in his honor on May 20, 2022. Th ...
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Chapter · January 1, 2023
All transplanted allografts undergo immune-mediated rejection unless the recipient immune response is modified in some way. Induction of immune tolerance is an oft-touted goal in the field of organ transplantation. This chapter highlights the mechanisms of ...
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Journal ArticleKidney360 · December 29, 2022
Preexisting donor-specific antibodies (DSA) to MHC antigens increase the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pretransplant desensitization with costimulation blockade and proteasome inhi ...
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Journal ArticlePediatr Transplant · December 2022
BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immun ...
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Journal ArticleSurgery · December 2022
BACKGROUND: An emerging body of literature supports the role of individualized prognostic tools to guide the management of patients after trauma. The aim of this study was to develop advanced modeling tools from multidimensional data sources, including imm ...
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Journal ArticleCrit Care Explor · December 2022
UNLABELLED: The COVID-19 pandemic has claimed over eight hundred thousand lives in the United States alone, with older individuals and those with comorbidities being at higher risk of severe disease and death. Although severe acute respiratory syndrome cor ...
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Journal ArticleAm J Transplant · October 2022
Health equity research in transplantation has largely relied on national data sources, yet the availability of social determinants of health (SDOH) data varies widely among these sources. We sought to characterize the extent to which national data sources ...
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Journal ArticleJ Trauma Acute Care Surg · October 1, 2022
INTRODUCTION: The pathophysiology of the inflammatory response after major trauma is complex, and the magnitude correlates with severity of tissue injury and outcomes. Study of infection-mediated immune pathways has demonstrated that cellular microRNAs may ...
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Journal ArticleJ Allergy Clin Immunol · September 2022
Establishing tolerance remains a central, if elusive, goal of transplantation. In solid-organ transplantation, one strategy for inducing tolerance has been cotransplantation of various forms of thymic tissue along with another organ. As one of the biologic ...
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Journal ArticleAnn Surg · June 1, 2022
OBJECTIVE: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing. BACKGROUND: Elective surgery is an opportunity to understand both the system ...
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Journal ArticleTransplantation · May 1, 2022
BACKGROUND: Activation of porcine endothelial cells (PECs) is the mechanistic centerpiece of xenograft rejection. This study sought to characterize the immuno-phenotype of human T cells in response to PECs and to explore the immuno-modulation of B7 and mam ...
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Journal ArticleCrit Care Med · February 1, 2022
OBJECTIVES: To evaluate early activation of latent viruses in polytrauma patients and consider prognostic value of viral micro-RNAs in these patients. DESIGN: This was a subset analysis from a prospectively collected multicenter trauma database. Blood samp ...
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Journal ArticleJ Immunol · February 1, 2022
Recent advancements in microfluidics and high-throughput sequencing technologies have enabled recovery of paired H and L chains of Igs and VDJ and VJ chains of TCRs from thousands of single cells simultaneously in humans and mice. Despite rhesus macaques b ...
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Journal ArticleBMJ Mil Health · December 2021
INTRODUCTION: Venous thromboembolism (VTE) is a frequent complication of trauma associated with high mortality and morbidity. Clinicians lack appropriate tools for stratifying trauma patients for VTE, thus have yet to be able to predict when to intervene. ...
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Journal ArticleTransplantation · December 1, 2021
BACKGROUND: Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how undernutrition and hypoleptinemia impact T-cell allospecific and cytomegalovirus (CMV) ...
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Journal ArticleAnn Surg Open · December 2021
OBJECTIVES: Integrate a predictive model for massive transfusion protocol (MTP) activation and delivery in the electronic medical record (EMR) using prospectively gathered data; externally validate the model and assess the accuracy and precision of the mod ...
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Journal ArticleSurgery · November 2021
BACKGROUND: Improper or delayed activation of a massive transfusion protocol may have consequences to individuals and institutions. We designed a complex predictive algorithm that was packaged within a smartphone application. We hypothesized it would accur ...
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Journal ArticleXenotransplantation · November 2021
Porcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-huma ...
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Journal ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · September 2021
Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the re ...
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Journal ArticleClin Transl Sci · September 2021
Traumatic injuries afflict more than 5 million people globally every year. Current and past animal research has demonstrated association among alcohol, trauma, and impaired immune function, whereas human registries have shown association between alcohol an ...
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Journal ArticleClin Transplant · August 2021
Rabbit antithymocyte globulin (RATG) preparations are widely used in transplantation. They are developed in vivo against thymocytes and contain polyclonal antibodies specific for myriad cellular targets. The rhesus monkey is commonly used as a preclinical ...
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Journal ArticleJ Trauma Acute Care Surg · July 1, 2021
BACKGROUND: Flow cytometry (FCM) is a rapid diagnostic tool for monitoring immune cell function. We sought to determine if assessment of cell phenotypes using standardized FCM could be used to identify nosocomial infection after trauma. METHODS: Prospectiv ...
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Journal ArticleAm J Transplant · June 2021
Despite extraordinary achievements in over the past 20 years, the field of transplantation remains hindered by relatively narrow metrics for success. Eudaimonia is an Aristotelian concept that refers to flourishing, or achieving the best conditions possibl ...
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Journal ArticleAm J Transplant · May 2021
Kidney transplant recipients administered belatacept-based maintenance immunosuppression present with a more favorable metabolic profile, reduced incidence of de novo donor-specific antibodies (DSAs), and improved renal function and long-term patient/graft ...
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Journal ArticleXenotransplantation · May 2021
BACKGROUND: Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins of thrombosis after islet xenotransplantation and relate it to early inflammation, we examined porcine islets tran ...
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Journal ArticleJ Immunol · April 1, 2021
Costimulation blockade (CoB)-based immunosuppression offers the promise of improved transplantation outcomes with reduced drug toxicity. However, it is hampered by early acute rejections, mediated at least in part by differentiated, CoB-resistant T cells, ...
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Journal ArticleInfect Control Hosp Epidemiol · March 2021
We implemented universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing of patients undergoing surgical procedures as a means to conserve personal protective equipment (PPE). The rate of asymptomatic coronavirus disease 2019 (COVID-19 ...
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Journal ArticleTranspl Int · March 2021
Vascularized composite allotransplants (VCAs) seem to have several unique features of clinical and experimental importance, including uniquely definable lymphatic drainage that can be easily accessed at the level of ipsilateral regional node beds. Thus, VC ...
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Journal ArticleAnn Surg Open · March 2021
The history of modern American surgery is marked by larger-than-life pioneers who have made transformative contributions to our field. These extraordinary individuals have been known primarily for their technical and clinical mastery, development of novel ...
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Journal ArticleAm J Transplant · February 2021
Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Ped ...
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Journal ArticleFront Immunol · 2021
BACKGROUND: The immunologic pathways activated during snakebite envenoming (SBE) are poorly described, and their association with recovery is unclear. The immunologic response in SBE could inform a prognostic model to predict recovery. The purpose of this ...
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Journal ArticleFront Immunol · 2021
BACKGROUND: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling m ...
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Journal ArticleAm J Transplant · December 2020
Kidney transplant outcomes are limited by toxicities associated with calcineurin inhibitors and steroids. This trial was conducted to determine whether a costimulation blockade (CoB)-based regimen could achieve acceptable long-term outcomes and graft survi ...
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Journal ArticleJ Autoimmun · December 2020
The T-cell response is regulated by the balance between costimulatory and coinhibitory signals. Immune checkpoints are essential for efficient T-cell activation, but also for maintaining self-tolerance and protecting tissues from damage caused by the immun ...
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Journal ArticleTranspl Int · October 2020
Vascularized composite allotransplantation (VCA) is challenged by the morbidity of immunosuppression required to prevent rejection. The use of highly specific biologics has not been well explored in VCA. Given that psoriasis is T-cell mediated, as is rejec ...
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Journal ArticleSurgery · October 2020
BACKGROUND: Post-traumatic acute kidney injury has occurred in every major military conflict since its initial description during World War II. To ensure the proper treatment of combat casualties, early detection is critical. This study therefore aimed to ...
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Journal ArticleHepatology · August 2020
BACKGROUND AND AIMS: As conversion from calcineurin inhibitor to sirolimus (SRL), a mechanistic target of rapamycin inhibitor (mTOR-I), has been shown to enhance immunoregulatory profiles in liver transplant (LT) recipients (LTRs), mTOR-I therapy might all ...
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Journal ArticleWorld J Surg · July 2020
BACKGROUND: Tools to assist clinicians in predicting pneumonia could lead to a significant decline in morbidity. Therefore, we sought to develop a model in combat trauma patients for identifying those at highest risk of pneumonia. METHODS: This was a retro ...
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Journal ArticleWorld J Surg · July 2020
In the original article, the units indicated on the y-axes of Fig. 3 are incorrectly labelled. The correct label is pg/mL. Following is the corrected Fig. 3. ...
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Journal ArticleJCI Insight · June 4, 2020
Eighty-six infants born without a thymus have been treated with allogeneic cultured thymus tissue implantation (CTTI). These infants, who lack T cells and are profoundly immunodeficient at birth, after CTTI from an unmatched donor develop T cells similar t ...
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Journal ArticleAm J Transplant · June 2020
Xenogeneic porcine islet transplantation is a promising potential therapy for type 1 diabetes (T1D). Understanding human immune responses against porcine islets is crucial for the design of optimal immunomodulatory regimens for effective control of xenogen ...
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Journal ArticleAnesth Analg · April 2020
Preoperative assessment typically equates to evaluating and accepting the presenting condition of the patient (unless extreme) and commonly occurs only a few days before the planned surgery. While this timing enables a preoperative history and examination ...
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Journal ArticleAm J Transplant · March 2020
Adolescent transplant recipients are at risk for nonadherence, development of de novo donor-specific antibody (dnDSA), and allograft loss. Belatacept, a selective T cell costimulatory blocker, is associated with reduced dnDSA, improved renal function, and ...
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Journal ArticleAm J Transplant · March 2020
Lymphocyte depletion has been shown to control costimulation blockade-resistant rejection but, in some settings, to exacerbate antibody-mediated rejection (AMR). We have used alemtuzumab, which depletes T and B cells, combined with belatacept and rapamycin ...
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Journal ArticleJ Am Coll Surg · March 2020
BACKGROUND: Significant analysis errors can be caused by nonvalidated data quality of electronic health records data. To determine surgical data fitness, a framework of foundational and study-specific data analyses was adapted and assessed using conformanc ...
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Journal ArticleJ Trauma Acute Care Surg · March 2020
BACKGROUND: The timing of coverage of an open wound is based on heavily on clinical gestalt. DoD's Surgical Critical Care Initiative created a clinical decision support tool that predicts wound closure success using clinical and biomarker data. The militar ...
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Journal ArticleTheranostics · 2020
Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To dev ...
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Journal ArticleXenotransplantation · November 2019
BACKGROUND: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value ...
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ConferenceJ Trauma Acute Care Surg · November 2019
BACKGROUND: Identifying clinical and biomarker profiles of trauma patients may facilitate the creation of models that predict postoperative complications. We sought to determine the utility of modeling for predicting severe sepsis (SS) and organ space infe ...
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Journal ArticleAnn Surg · September 2019
BACKGROUND: Both the frequency and high complication rates associated with extremity wounds in recent military conflicts have highlighted the need for clinical decision support tools (CDST) to decrease time to wound closure and wound failure rates. METHODS ...
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Journal ArticleJCI Insight · August 22, 2019
Multiple organ failure (MOF) is the leading cause of late mortality and morbidity in patients who are admitted to intensive care units (ICUs). However, there is an epidemiologic discrepancy in the mechanism of underlying immunologic derangement dependent o ...
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Journal ArticleAm J Transplant · August 2019
Naïve T cell activation requires antigen presentation combined with costimulation through CD28, both of which optimally occur in secondary lymphoid tissues such as lymph nodes and the spleen. Belatacept impairs CD28 costimulation by binding its ligands, CD ...
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Journal ArticleAm J Transplant · July 2019
The innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. ...
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Journal ArticleClin Transplant · June 2019
Belatacept, the CD28-B7 costimulation pathway inhibitor, has been approved as a calcineurin inhibitor (CNI) alternative in kidney transplantation. Although costimulation blockade (CoB) allows for CNI avoidance, it is associated with increased rates of earl ...
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Journal ArticleCrit Care Med · December 2018
OBJECTIVES: Extracellular mitochondrial DNA and N-formyl peptides released following tissue damage may contribute to systemic inflammation through stimulation of the innate immune system. In this review, we evaluate existing in vivo human data regarding a ...
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Journal ArticleJ Surg Res · November 2018
BACKGROUND: Surgical insult and trauma have been shown to cause dysregulation of the immune and inflammatory responses. Interaction of damage-associated molecular patterns (DAMPs) with toll-like receptors (TLRs) initiates innate immune response and systemi ...
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Journal ArticleAm J Transplant · July 2018
Most immunosuppressive regimens used in clinical vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)-based. As such, most recipients have experienced CNI-related side effects. Costimulation blockade, specifically CD28/B7 ...
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Journal ArticleAm J Transplant · April 2018
Porcine islet xenografts have the potential to provide an inexhaustible source of islets for β cell replacement. Proof-of-concept has been established in nonhuman primates. However, significant barriers to xenoislet transplantation remain, including the po ...
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Journal ArticleAm J Transplant · March 2018
Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated w ...
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ConferenceMil Med · March 1, 2018
Precision medicine endeavors to leverage all available medical data in pursuit of individualized diagnostic and therapeutic plans to improve patient outcomes in a cost-effective manner. Its promise in the field of critical care remains incompletely realize ...
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Journal ArticleJ Med Primatol · February 2018
Recrudescence of latent and dormant viruses may lead to overwhelming viremia in immunosuppressed hosts. In immunocompromised hosts, Simian virus 40 (SV40) reactivation is known to cause nephritis and demyelinating central nervous system disease. Here, we r ...
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Journal ArticleJ Clin Neurosci · February 2018
Extensive pre-clinical and clinical studies have searched for therapeutic efficacy of cell-based therapeutics in diseases of the Central Nervous System (CNS) with no other viable options. Allogeneic cells represent the primary source of these therapies and ...
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Journal ArticleFront Immunol · 2018
CD28:CD80/86 pathway costimulation blockade (CoB) with the CD80/86-specific fusion protein CTLA4-Ig prevents T cell-mediated allograft rejection in mice. However, in humans, transplantation with CoB has been hampered by CoB-resistant rejection (CoBRR). CoB ...
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Journal ArticleFront Immunol · 2018
Despite its excellent efficacy in controlling T cell mediated acute rejection, lymphocyte depletion may promote a humoral response. While T cell repopulation after depletion has been evaluated in many aspects, the B cell response has not been fully elucida ...
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Journal ArticleBlood Adv · November 14, 2017
The detrimental effects of donor-directed antibodies in sensitized transplant patients remain a difficult immunologic barrier to successful organ transplantation. Antibody removal is often followed by rebound. Proteasome inhibitors (PIs) deplete antibody-p ...
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Journal ArticleAm J Transplant · November 2017
Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in ...
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Journal ArticleJ Trauma Acute Care Surg · October 2017
BACKGROUND: The biomarker profile of trauma patients may allow for the creation of models to assist bedside decision making and prediction of complications. We sought to determine the utility of modeling in the prediction of bacteremia and pneumonia in com ...
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Journal ArticleAm J Transplant · June 2017
The Immune Development in Pediatric Transplantation (IMPACT) study was conducted to evaluate relationships among alloimmunity, protective immunity, immune development, physical parameters, and clinical outcome in children undergoing kidney transplantation. ...
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Journal ArticleAm J Transplant · May 2017
Costimulation blockade (CoB) via belatacept is a lower-morbidity alternative to calcineurin inhibitor (CNI)-based immunosuppression. However, it has higher rates of early acute rejection. These early rejections are mediated in part by memory T cells, which ...
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Journal ArticleJ Clin Monit Comput · April 2017
Improving diagnosis and treatment depends on clinical monitoring and computing. Clinical decision support systems (CDSS) have been in existence for over 50 years. While the literature points to positive impacts on quality and patient safety, outcomes, and ...
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Journal ArticleAm J Transplant · March 2017
Although stable mixed-hematopoietic chimerism induces robust immune tolerance to solid organ allografts in mice, the translation of this strategy to large animal models and to patients has been challenging. We have previously shown that in MHC-matched nonh ...
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Journal ArticleAm J Transplant · March 2017
An unbalanced microbiome may lead to disease by creating aberrant immune responses. A recent association of cellular rejection with the development of interstitial fibrosis and tubular atrophy (IFTA) suggests the role of immune-mediated tissue injury. We h ...
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Journal ArticleBiomaterials · March 2017
Trauma patients produce a host of danger signals and high levels of damage-associated molecular patterns (DAMPs) after cellular injury and tissue damage. These DAMPs are directly and indirectly involved in the pathogenesis of various inflammatory and throm ...
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Journal ArticleJ Am Soc Nephrol · January 2017
An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regardi ...
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Journal ArticleFront Med (Lausanne) · 2017
Despite potent immunosuppression, clinical and biopsy confirmed acute renal allograft rejection (AR) still occurs in 10-15% of recipients, ~30% of patients demonstrate subclinical rejection on biopsy, and ~50% of them can show molecular inflammation, all w ...
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Journal ArticleAm J Transplant · December 2016
The pathophysiological importance of the immunogenicity of damage-associated molecular patterns (DAMPs) has been pinpointed by their identification as triggers of allograft rejection following release from dying cells, such as after ischemia-reperfusion in ...
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Journal ArticleAm J Transplant · September 2016
Previously, we demonstrated that alemtuzumab induction with rapamycin as sole maintenance therapy is associated with an increased incidence of humoral rejection in human kidney transplant patients. To investigate the role of rapamycin in posttransplant hum ...
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Journal ArticleStem Cells · September 2016
We have previously demonstrated that cryopreservation and thawing lead to altered Mesenchymal stromal cells (MSC) functionalities. Here, we further analyzed MSC's fitness post freeze-thaw. We have observed that thawed MSC can suppress T-cell proliferation ...
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Journal ArticleNat Rev Nephrol · June 2016
Antigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid re ...
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Journal ArticleAm J Transplant · May 2016
Featured Publication
Costimulation blockade with the fusion protein belatacept provides a desirable side effect profile and improvement in renal function compared with calcineurin inhibition in renal transplantation. This comes at the cost of increased rates of early acute rej ...
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Journal ArticleAm J Transplant · April 2016
Featured Publication
Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate co ...
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Journal ArticleAm J Transplant · February 2016
Featured Publication
Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was c ...
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Journal ArticleTransplantation · January 2016
Featured Publication
BACKGROUND: Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impac ...
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Journal ArticleXenotransplantation · 2016
Featured Publication
In 2009, the International Xenotransplantation Association (IXA) published a consensus document that provided guidelines and "recommendations" (not regulations) for those contemplating clinical trials of porcine islet transplantation. These guidelines incl ...
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Journal ArticlePLoS One · 2016
BACKGROUND: Apolipoprotein L1 gene (APOL1) G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor ...
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Journal ArticleAm J Transplant · November 2015
Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transpl ...
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Journal ArticlePediatr Cardiol · October 2015
Featured Publication
Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized tha ...
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Chapter · September 12, 2015
Organ transplantation is the accepted and indeed the preferred treatment for most forms of end-stage organ failure. While the function of the immune system may be to protect against infection or "danger", the immune system, if not suppressed, also efficien ...
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Journal ArticleKidney Int · September 2015
Variants in donor multidrug resistance protein 1 (ABCB1) and caveolin 1 (CAV1) genes are associated with renal allograft failure after transplantation in Europeans. Here we assessed transplantation outcomes of kidneys from 368 African American (AA) and 314 ...
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Journal ArticleEBioMedicine · September 2015
BACKGROUND: Recent conflicts in Afghanistan and Iraq produced a substantial number of critically wounded service-members. We collected biomarker and clinical information from 73 patients who sustained 116 life-threatening combat wounds, and sought to deter ...
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Journal ArticleAm J Transplant · August 2015
Featured Publication
Vascularized composite allotransplantation (VCA) has emerged as a viable limb replacement strategy for selected patients with upper limb amputation. However, allograft rejection has been seen in essentially all reported VCA recipients indicating a requirem ...
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Journal ArticleAm J Transplant · August 2015
Featured Publication
Vascularized composite allografts (VCAs) are technically feasible. Similar to other organ transplants, VCAs are hampered by the toxicity and incomplete efficacy associated with conventional immunosuppression. Complications attributable to calcineurin inhib ...
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Journal ArticleBlood · June 18, 2015
Although cytomegalovirus (CMV) reactivation has long been implicated in posttransplant immune dysfunction, the molecular mechanisms that drive this phenomenon remain undetermined. To address this, we combined multiparameter flow cytometric analysis and T-c ...
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Journal ArticleBlood · June 18, 2015
Although cytomegalovirus (CMV) reactivation has long been implicated in posttransplant immune dysfunction, the molecular mechanisms that drive this phenomenon remain undetermined. To address this, we combined multiparameter flow cytometric analysis and T-c ...
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Journal ArticleJ Surg Res · June 15, 2015
Featured Publication
BACKGROUND: Belatacept, a B7-specific fusion protein, blocks CD28-B7 costimulation and prevents kidney allograft rejection. However, it is ineffective in a sizable minority of patients. Although T-cell receptor and CD28 engagement are known to initiate T-c ...
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Journal ArticleAm J Transplant · June 2015
Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from ...
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Journal ArticleAm J Transplant · May 2015
Islet xenotransplantation is a potential treatment for diabetes without the limitations of tissue availability. Although successful experimentally, early islet loss remains substantial and attributed to an instant blood-mediated inflammatory reaction (IBMI ...
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Journal ArticleAm J Transplant · April 2015
Featured Publication
Costimulation blockade with the B7-CD28 pathway-specific agent belatacept is now used in clinical kidney transplantation, but its efficacy remains imperfect. Numerous alternate costimulatory pathways have been proposed as targets to synergize with belatace ...
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Journal ArticleHepatology · March 2015
UNLABELLED: Chronic liver disease is characterized by the liver enrichment of myeloid dendritic cells (DCs). To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem ...
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Journal ArticleAm J Transplant · December 2014
Many critical issues remain concerning how best to deploy adoptive regulatory T cell (Treg) immunotherapy to the clinic. These include a determination of their pharmacokinetic characteristics, their optimal dose, their phenotypic stability and the best the ...
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Journal ArticleAm J Physiol Gastrointest Liver Physiol · December 1, 2014
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Ischemia-reperfusion injury (IRI) is a common clinical consequence of hepatic surgery, cardiogenic shock, and liver transplantation. A steatotic liver is particularly vulnerable to IRI, responding with extensive hepatocellular injury. Autophagy, a lysosoma ...
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Journal ArticleAm J Transplant · November 2014
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CD28 is a primary costimulation molecule for T cell activation. However, during the course of activation some T cells lose this molecule and assume a CD28-independent existence. These CD28- T cells are generally antigen-experienced and highly differentiate ...
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Journal ArticlePLoS Med · November 2014
BACKGROUND: Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic a ...
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Journal ArticleStem Cell Reports · July 8, 2014
Mesenchymal stromal cells have shown clinical promise; however, variations in treatment responses are an ongoing concern. We previously demonstrated that MSCs are functionally stunned after thawing. Here, we investigated whether this cryopreservation/thawi ...
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Journal ArticleAm J Transplant · May 2014
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Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. Belatacept is a less toxic CNI alternative, but existing regimens rely on steroids and have higher rejection rates. Experimentally, donor bone marrow and si ...
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Journal ArticleNat Rev Nephrol · April 2014
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The immune management of organ transplant recipients is imperfect. Beyond general dosing guidelines for immunosuppressive agents and clinical diagnostic tests for rejection or infection, there are few objective tools to determine the aggregate status of a ...
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Journal ArticleAm J Transplant · April 2014
Aspiration of gastrointestinal contents has been linked to worse outcomes following lung transplantation but uncertainty exists about underlying mechanisms. We applied high-resolution metabolomics of bronchoalveolar lavage fluid (BALF) in patients with epi ...
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Journal ArticleAm J Transplant · April 2014
The impact of donor-specific HLA alloantibodies (DSA) on short- and long-term liver transplant outcome is not clearly defined. While it is clear that not all levels of allosensitization produce overt clinical injury, and that liver allografts possess some ...
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Journal ArticleAm J Transplant · March 2014
The CD28/cytotoxic T-lymphocyte antigen 4 (CTLA-4)blocker belatacept selectively inhibits alloreactive T cell responses but is associated with a high incidence of acute rejection following renal transplantation,which led us to investigate the etiology of b ...
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Journal ArticleImmunol Rev · March 2014
One's cellular immune repertoire is composed of lymphocytes in multiple stages of maturation - the dynamic product of their responses to antigenic challenges and the homeostatic contractions necessary to accommodate immune expansions within physiologic nor ...
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Journal ArticleAm J Transplant · February 2014
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Tacrolimus impairs allo- and viral-specific T cell responses. Belatacept, a costimulation-based alternative to tacrolimus, has emerged with a paradoxical picture of less complete control of alloimmunity with concomitant impaired viral immunity limited to v ...
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Journal ArticleXenotransplantation · 2014
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Type I diabetes remains a significant clinical problem in need of a reliable, generally applicable solution. Both whole organ pancreas and islet allotransplantation have been shown to grant patients insulin independence, but organ availability has restrict ...
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Journal ArticleAm J Transplant · January 2014
De novo donor-specific antibody (DSA) after organ transplantation promotes antibody-mediated rejection (AMR) and causes late graft loss. Previously, we demonstrated that depletion using anti-CD3 immunotoxin combined with tacrolimus and alefacept (AMR regim ...
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Journal ArticleAm J Transplant · December 2013
The integrin αvβ6 activates latent transforming growth factor-β (TGF-β) within the kidney and may be a target for the prevention of chronic allograft fibrosis after kidney transplantation. However, TGF-β also has known immunosuppressive properties that are ...
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Journal ArticleBiol Blood Marrow Transplant · November 2013
We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/m ...
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Journal ArticleTransplantation · August 15, 2013
BACKGROUND: Calcineurin is a ubiquitously expressed calcium-dependent phosphatase that is inhibited by the immunosuppressant drugs cyclosporine and tacrolimus. Measuring calcineurin activity in transplant patients has been complicated by a lack of consiste ...
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Journal ArticleAm J Transplant · April 2013
Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver-kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody-mediated kidney rejection. To further investigate the ris ...
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Journal ArticleAm J Transplant · February 2013
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Calcineurin inhibitors (CNI) and steroids are known to promote insulin resistance, and their avoidance after islet transplantation is preferred from a metabolic standpoint. Belatacept, a B7-specific mediator of costimulation blockade (CoB), is clinically i ...
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Journal ArticleAm J Transplant · February 2013
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Belatacept is an inhibitor of CD28/B7 costimulation that is clinically indicated as a calcineurin inhibitor (CNI) alternative in combination with mycophenolate mofetil and steroids after renal transplantation. We sought to develop a clinically translatable ...
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Journal ArticlePLoS One · 2013
The mechanisms underlying latent-virus-mediated heterologous immunity, and subsequent transplant rejection, especially in the setting of T cell costimulation blockade, remain undetermined. To address this, we have utilized MHV68 to develop a rodent model o ...
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Journal ArticleHepatology · December 2012
UNLABELLED: Chronic hepatitis C virus (HCV) infection is a serious disease that can result in numerous long-term complications leading to liver failure or death. Approximately 80% of people fail to clear their infection, largely as the result of weak, narr ...
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Journal ArticleTransplantation · November 15, 2012
BACKGROUND: Hyperlipidemia is a common adverse effect of sirolimus (SRL). We previously showed significant associations of ABCB1 3435C>T and IL-10 -1082G>A with log-transformed SRL dose-adjusted weighted-normalized trough. We further examined to see whethe ...
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Journal ArticleAm J Pathol · November 2012
Nonalcoholic fatty liver disease is an increasingly prevalent spectrum of conditions characterized by excess fat deposition within hepatocytes. Affected hepatocytes are known to be highly susceptible to ischemic insults, responding to injury with increased ...
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Journal ArticleAm J Transplant · November 2012
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CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, ...
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Journal ArticleAm J Transplant · October 2012
Even though the etiology of chronic rejection (CR) is multifactorial, donor specific antibody (DSA) is considered to have a causal effect on CR development. Currently the antibody-mediated mechanisms during CR are poorly understood due to lack of proper an ...
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Journal ArticleAm J Transplant · August 2012
The importance of CD40/CD154 costimulatory pathway blockade in immunosuppression strategies is well-documented. Efforts are currently focused on monoclonal antibodies specific for CD40 because of thromboembolic complications associated with monoclonal anti ...
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Journal ArticleAm J Transplant · July 2012
Islet transplantation to treat type 1 diabetes has been limited in part by toxicities of current immunosuppression and recipient humoral sensitization. Blockade of the CD28/CD80/86 and CD40/CD154 pathways has shown promise to remedy both these limitations, ...
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Journal ArticleAm J Transplant · July 2012
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Immunosuppressive therapies that block the CD40/CD154 costimulatory pathway have proven to be uniquely effective in preclinical xenotransplant models. Given the challenges facing clinical translation of CD40/CD154 pathway blockade, we examined the efficacy ...
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Journal ArticleAm J Transplant · July 2012
Although there is evidence linking hematopoietic chimerism induction and solid organ transplant tolerance, the mechanistic requirements for chimerism-induced tolerance are not clearly elucidated. To address this, we used an MHC-defined primate model to det ...
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Journal ArticleAm J Transplant · June 2012
Although regulatory T cells (Tregs) suppress allo-immunity, difficulties in their large-scale production and in maintaining their suppressive function after expansion have thus far limited their clinical applicability. Here we have used our nonhuman primat ...
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Journal ArticleJ Am Soc Nephrol · May 2012
The effect of CKD on the risks of bariatric surgery is not well understood. Using the American College of Surgeons National Surgical Quality Improvement Program Participant Use File, we analyzed 27,736 patients who underwent bariatric surgery from 2006 thr ...
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Journal ArticleAm J Transplant · February 2012
Outcomes following lung transplant are suboptimal owing to chronic allograft failure termed bronchiolitis obliterans syndrome (BOS). Prior work in both mice and humans has shown that interferon gamma (IFNG)-induced chemokines, including CXCL9 and CXCL10, a ...
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Chapter · 2012
Many drugs are used to prevent allograft rejection. Most target T cells but inhibit pathways that are not exclusive to T cells and thus evoke off-target side effects. Many, particularly calcineurin inhibitors, hinder T cell receptor (TCR) signaling and thu ...
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Journal ArticleAm J Transplant · January 2012
In murine models, T-cell costimulation blockade of the CD28:B7 and CD154:CD40 pathways synergistically promotes immune tolerance after transplantation. While CD28 blockade has been successfully translated to the clinic, translation of blockade of the CD154 ...
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Journal ArticleAm J Transplant · January 2012
The success of belatacept in late-stage clinical trials inaugurates the arrival of a new class of immunosuppressants based on costimulatory blockade, an immunosuppression strategy that disrupts essential signals required for alloreactive T-cell activation. ...
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Journal ArticleAm J Transplant · January 2012
Costimulation blockade of the CD40/CD154 pathway has been effective at preventing allograft rejection in numerous transplantation models. This strategy has largely depended on mAbs directed against CD154, limiting the potential for translation due to its a ...
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Journal ArticleTransplantation · December 27, 2011
BACKGROUNDS: Sirolimus (SRL) absorption and metabolism are affected by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of a ...
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Journal ArticleProc Natl Acad Sci U S A · December 20, 2011
Blockade of the CD40/CD154 pathway potently attenuates T-cell responses in models of autoimmunity, inflammation, and transplantation. Indeed, CD40 pathway blockade remains one of the most powerful methods of prolonging graft survival in models of transplan ...
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Journal ArticleAm J Transplant · December 2011
Significant deficiencies in understanding of xenospecific immunity have impeded the success of preclinical trials in xenoislet transplantation. Although galactose-α1,3-galactose, the gal epitope, has emerged as the principal target of rejection in pig-to-p ...
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Journal ArticleTransplant Proc · December 2011
Outcomes following lung transplant remain suboptimal. This is attributable to variable posttransplant recovery of lung function, and inconsistent degrees of lung function loss after peak function is reached. Granzyme B is elevated in the blood and bronchoa ...
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Journal ArticleBlood · November 24, 2011
Despite encouraging results using lymphocyte function antigen-1 (LFA-1) blockade to inhibit BM and solid organ transplantation rejection in nonhuman primates and humans, the precise mechanisms underlying its therapeutic potential are still poorly understoo ...
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Journal ArticleAm J Transplant · October 2011
Renal transplant recipients require periodic surveillance for immune-based complications such as rejection and infection. Noninvasive monitoring methods are preferred, particularly for children, for whom invasive testing is problematic. We performed a cros ...
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Journal ArticleAmerican Journal of Transplantation · September 1, 2011
A look at AJT's past year, and at features anticipated in the coming year. ...
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Journal ArticleAm J Transplant · June 2011
The presence of preformed, donor-specific alloantibodies inpatients undergoing renal transplantation is associated with a high risk of hyperacute and acute antibody-mediated rejection (ABMR), and often limits potential recipients' access to organs from liv ...
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Journal ArticleAm J Transplant · May 2011
The widespread clinical implementation of alloislet transplantation as therapy for type 1 diabetes has been hindered by the lack of suitable islet donors. Pig-to-human islet xenotransplantation is one strategy with potential to alleviate this shortage. Lon ...
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Journal ArticleAm J Transplant · March 2011
Sirolimus is a potent antiproliferative agent used clinically to prevent renal allograft rejection. However, little is known about the effects of maintenance immunosuppressive agents on the immune response to potentially protective vaccines. Here we show t ...
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Journal ArticleTransplantation · January 15, 2011
BACKGROUND: Chemokines and their receptors play a critical role in leukocyte trafficking, and inhibition of select chemokines has been shown to attenuate kidney disease and allograft rejection in animal models. Therefore, we evaluated chemokine and chemoki ...
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Journal ArticleAm J Transplant · January 2011
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Costimulation blockade (CoB), specifically CD28/B7 inhibition with belatacept, is an emerging clinical replacement for calcineurin inhibitor-based immunosuppression in allotransplantation. However, there is accumulating evidence that belatacept incompletel ...
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Journal ArticleJ Clin Invest · December 2010
Outcomes in transplantation have been limited by suboptimal long-term graft survival and toxicities associated with current immunosuppressive approaches. T cell costimulation blockade has shown promise as an alternative strategy to avoid the side effects o ...
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Journal ArticleNat Rev Nephrol · October 2010
Transplantation tolerance is a state of immune unresponsiveness (or benign responsiveness) to the presence of specific, nonself antigens in the absence of chronic immunosuppressive therapy. Renal transplant tolerance remains a desired yet generally unattai ...
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Journal ArticleChest · October 2010
BACKGROUND: Lung transplantation is associated with a high incidence of gastroesophageal reflux disease (GERD). The presence of GERD is considered a risk factor for the subsequent development of obliterative bronchiolitis (OB), and surgical correction of G ...
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Journal ArticleCurr Opin Immunol · October 2010
It is well recognized that allospecific T cell activation is required for rejection. However, the process of allospecific T cell activation is largely controllable with current agents. Accordingly, short-term outcomes in allotransplantation have uniformly ...
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Journal ArticleAm J Transplant · September 2010
Islet transplantation is an experimental therapy for selected patients with type 1 diabetes (T1DM). It remains limited by immunosuppressive drug toxicity, progressive loss of insulin independence, allosensitization and the need for multiple islet donors. W ...
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Journal ArticleJ Immunol · August 15, 2010
Recent evidence demonstrating that exposure to rapamycin during viral infection increased the quantity and quality of Ag-specific T cells poses an intriguing paradox, because rapamycin is used in transplantation to dampen, rather than enhance, donor-reacti ...
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Journal ArticleJ Clin Invest · June 2010
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Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefi ...
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Journal ArticleTransplantation · May 27, 2010
BACKGROUND: Blockade of costimulatory molecules is a potent method of inducing long-term graft survival. We have previously addressed the issue of donor-reactive T-cell precursor frequency on relative costimulation dependence and found that the presence of ...
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OtherAm J Transplant · March 2010
When new agents such as bortezomib appear, it is important to maintain scientific rigor regarding off-label use of medications. ...
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Journal ArticleJ Immunol · March 1, 2010
Costimulatory signals via B7/CD28 family molecules (signal 2) are critical for effective adaptive CD8(+) T cell immune responses. In addition to costimulatory signals, B7/CD28 family coinhibitory receptor/ligands that modulate immune responses have been id ...
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Journal ArticleClin Transplant · 2010
In a cohort of 32 renal transplant patients who are potentially at risk for adverse events, we compared tacrolimus (TAC) abbreviated AUC values calculated by a method developed in Asians (AUCw) with those derived for Caucasians (AUCa). The relationships be ...
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Journal ArticleRevue Francophone des Laboratoires · January 1, 2010
The recognition of microbes by the innate immune system is mediated by a family of receptors called pattern recognition receptor (PRR). The specificity of PRR is genetically determined and their main function is to discriminate self from non self via the r ...
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Journal ArticleRevue Francophone des Laboratoires · January 1, 2010
Primary immunodeficiency diseases involve innate and adaptive immunity. In humans, about 150 Mendelian conditions involving impaired immune response have been described. Variable disease expression, even with the same mutation, is commonly observed.Diagnos ...
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Journal ArticleRevue Francophone des Laboratoires · January 1, 2010
Over two decades ago, CD4+ T cells were classified into various T cell subsets. Each subset is characterised by its specific cytokine pattern and effector functions in the immune response. This classification has long been confined to two subsets of helper ...
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Journal ArticleCurr Opin Organ Transplant · December 2009
PURPOSE OF REVIEW: This review details the role of memory T cells in physiologic and allospecific immunity, and summarizes the effects of immunosuppressive agents used to manipulate their function in the context of organ transplantation. RECENT FINDINGS: M ...
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Journal ArticleAm J Transplant · November 2009
The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplan ...
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Journal ArticleTransplantation · August 27, 2009
BACKGROUND: Despite advances in the field of lung transplantation, the median survival after lung transplant remains below 5 years. Early rejection is a risk factor for the development of chronic rejection. In animal models of transplant tolerance, regulat ...
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Journal ArticleTranspl Int · July 2009
Monocyte accumulation in renal allografts is associated with allograft dysfunction. As monocyte influx occurs acutely following reperfusion, we investigated the effect of ischemia-reperfusion injury (IRI) on monocyte colony stimulating factor (m-CSF), a ke ...
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Journal ArticleNat Med · July 2009
Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates ...
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Journal ArticleBrain · June 2009
Sporadic inclusion-body myositis (sIBM) is the most common disabling, adult-onset, inflammatory myopathy histologically characterized by intense inflammation and vacuolar degeneration. In spite of T cell-mediated cytotoxicity and persistent, clonally expan ...
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Journal ArticleTransplantation · May 15, 2009
Blockade of T-cell costimulatory pathways represents a potent and specific method of preventing naïve antidonor T-cell responses after transplantation in mouse, monkey, and man. However, numerous studies have shown that the presence of donor-reactive memor ...
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Journal ArticleTransplantation · April 27, 2009
Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and resistance (R). We investigated infrared (IR) imaging during PP as a means for precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr of PP in an un ...
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Journal ArticleTransplantation · April 15, 2009
In 2008, three publications highlighted the transition of tolerance from experimental to experiential. These included the first study to both anticipate and reproducibly deliver human leukocyte antigen-disparate allograft survival without continuous immuno ...
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Journal ArticleTransplant Rev (Orlando) · January 2009
Alloantigen exposure typically provokes an adaptive immune response that can foster rejection of transplanted organs, and these responses present the most formidable biological barrier to kidney transplantation. Although most cellular alloimmune responses ...
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Journal ArticleAm J Transplant · January 2009
Pretransplant exposure to donor antigen is known to modulate recipient alloimmunity, and frequently results in sensitization. However, donor-specific transfusion (DST) can have a protolerant effect that is dependent on route, dose and coadministered immuno ...
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Journal ArticleAm J Transplant · January 2009
This review relates the basic functions of platelets to specific aspects of organ allograft rejection. Platelet activation can occur in the donor or recipient before transplantation as well as during antibody- and cell-mediated rejection. Biopsies taken du ...
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Journal ArticleJ Immunol · January 1, 2009
CD8 T cells are necessary for costimulation blockade-resistant rejection. However, the mechanism by which CD8 T cells mediate rejection in the absence of major costimulatory signals is poorly understood. IFN-gamma promotes CD8 T cell-mediated immune respon ...
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Journal ArticleTranspl Immunol · November 2008
National registry data indicate a trend towards the incorporation of lymphocyte depletion antibody induction therapy into immunosuppressive regimens for solid organ transplantation. Depletional induction has been shown to reduce the risk of early acute rej ...
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Journal ArticleJ Immunol · October 15, 2008
Peripheral mechanisms of self-tolerance often depend on the quiescent state of the immune system. To what degree such mechanisms can be engaged in the enhancement of allograft survival is unclear. To examine the role of the PD-1 pathway in the maintenance ...
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Journal ArticleJ Surg Res · October 2008
BACKGROUND: Currently visual and tactile clues such as color, mottling, and tissue turgor are used in the operating room for subjective assessments of organ ischemia. Studies have demonstrated that infrared (IR) imaging is a reliable tool to identify perfu ...
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Journal ArticleAm J Transplant · October 2008
The first decade of the new millennium has been disappointing for transplant therapeutics: no new immunosuppression agents have been approved. Several high profile drugs and biologics failed the rigors of clinical trials or had disappointing preclinical re ...
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Journal ArticleAm J Transplant · July 2008
Composite tissue allotransplantation (CTA) is a recently introduced option for limb replacement and reconstruction of tissue defects. As with other allografts, CTA can undergo immune-mediated rejection; therefore standardized criteria are required for char ...
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Journal ArticleAm J Transplant · June 2008
Valganciclovir is commonly used for cytomegalovirus (CMV) prophylaxis in renal transplant patients. A fixed dose of 900 mg daily is typically recommended, however, there has never been a formal pharmacokinetic study comparing various doses in renal transpl ...
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Journal ArticleJ Immunol · June 1, 2008
Ag-specific precursor frequency is increasingly being appreciated as an important factor in determining the kinetics, magnitude, and degree of differentiation of T cell responses, and recently was found to play a critical role in determining the relative r ...
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Journal ArticleBMC Surg · April 17, 2008
BACKGROUND: Standard methods for assessment of organ viability during surgery are typically limited to visual cues and tactile feedback in open surgery. However, during laparoscopic surgery, these processes are impaired. This is of particular relevance dur ...
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Journal ArticleAm J Transplant · March 2008
Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely define ...
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Journal ArticleFront Biosci · January 1, 2008
Organ transplantation is an increasingly successful therapy for many forms of organ failure, but its success depends upon drug therapies to prevent immunologic destruction of the transplanted organ also known as rejection. Most therapies designed to preven ...
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Journal ArticleClin Transplant · 2008
Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-s ...
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Chapter · 2008
Tissues transferred between genetically nonidentical individuals are destroyed through a process known broadly as rejection. It has been apparent throughout most of medical history that these tissues could provide relief from disease if they were not rejec ...
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Chapter · January 1, 2008
Patients suffering from severe tissue loss secondary to burns, traumatic injuries, or tumor resections have limited options for reconstruction when autologous tissue for reconstruction is scarce. Composite tissue allotransplantation (CTA) has recently been ...
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Journal ArticleTransplantation · December 27, 2007
Alemtuzumab is a humanized CD52-specific monoclonal antibody that is increasingly used off-label as an induction agent in solid organ transplantation, particularly in the setting of maintenance immunosuppression minimization protocols. In this review, we b ...
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Journal ArticleAm J Transplant · November 2007
Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion i ...
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Journal ArticleJ Am Soc Nephrol · August 2007
Vascularized allografts are rejected unless some indefinite modification to the recipient's immune system is made. This modification is typically achieved through the long-term administration of immunosuppressive drugs. Patients thus trade their end-stage ...
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Journal ArticleSemin Nephrol · July 2007
Recent advancements in immunobiology have introduced several new diagnostic tools for monitoring kidney transplant recipients. These have been added to more established tests that, although imperfect, remain important benchmarks of diagnostic utility. Both ...
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Journal ArticleAm J Transplant · June 2007
There is growing awareness that B cells and alloantibodies are important mediators of both acute and chronic allograft injury. Unfortunately, few therapies are clinically available to mitigate the function of B cells or the effects of established alloantib ...
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Journal ArticleTransplantation · May 15, 2007
BACKGROUND: CD154-specific antibodies have been shown to prevent acute rejection in many preclinical models including nonhuman primates (NHPs). However, they have been ineffective in pilot clinical trials, suggesting a need for more robust preclinical anal ...
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Journal ArticleAm J Transplant · March 2007
A 1-day symposium on the application of protocol biopsies in renal transplantation was held in Boston, 21 July 2006. Representatives from centers with extensive experience in the use of protocol biopsies for routine patient care and research reported resul ...
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Journal ArticleTransplantation · September 15, 2006
Induction immunosuppression is intense, prophylactic therapy used at the time of transplantation based on the empiric observation that more powerful immunosuppression is required to prevent acute rejection early. In the past decade, there has been a growin ...
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Journal ArticleAm J Transplant · May 2006
Activated T cells orchestrate the immune response that results in graft rejection; therefore, a common goal among current immunosuppressive therapies is to block T-cell activation, proliferation and function. Current immunosuppressive regimens that inhibit ...
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Journal ArticleClin J Am Soc Nephrol · May 2006
Kidney biopsy is the gold standard procedure for the assessment of allograft dysfunction. The differential diagnosis for both acute and chronic dysfunction can encompass a number of different causes, and a biopsy frequently can suggest a specific cause. Ho ...
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Journal ArticleAm J Transplant · March 2006
Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population, and is often attributed to the necessary ...
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Journal ArticleJ Clin Invest · March 2006
CD154 is a cell surface molecule expressed on activated T cells that binds to CD40, an activating molecule on APCs. Its blockade has been shown to prevent allograft rejection, presumably by interrupting interactions between T cells and APCs. It is known th ...
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Journal ArticleTransplantation · February 15, 2006
BACKGROUND: Composite tissue allotransplantation (CTA) is a recently introduced option for limb replacement and reconstruction of other nonreconstructible tissue defects. As with recipients of other allotransplants, CTA recipients can experience rejection ...
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Journal ArticleJ Immunol · January 15, 2006
Recipient monocytes, T cells, and donor endothelial cells (ECs) are recognized as critical components of allograft rejection. We have recently shown that human monocytes infiltrate vascularized allografts before clinical rejection and have thus hypothesize ...
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Journal ArticleTransplantation · January 15, 2006
Enthusiasm for tolerance induction has been tempered by the realization that it is more difficult to achieve clinically than was predicted by experimental models. Unlike the view that the immune response to an allograft is ordered and thus predictable, we ...
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ConferenceProceedings of SPIE - The International Society for Optical Engineering · 2006
Many surgical techniques are currently shifting from the more conventional, open approach towards minimally invasive laparoscopic procedures. Laparoscopy results in smaller incisions, potentially leading to less postoperative pain and more rapid recoveries ...
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Journal ArticleTransplantation · December 27, 2005
BACKGROUND: Composite tissue allotransplantation (CTA) is a recently introduced option for limb replacement and reconstruction of other nonreconstructible tissue defects. As with recipients of other allotransplants, CTA recipients can experience rejection ...
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Journal ArticleAm J Transplant · December 2005
Understanding at a molecular level, the immunologic response of polyomavirus nephropathy (PVN), a critical cause of kidney graft loss, could lead to new targets for treatment and diagnosis. We undertook a transcriptional evaluation of kidney allograft biop ...
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Journal ArticleTranspl Immunol · December 2005
The current standard of care in transplantation reliably achieves acceptable graft and patient survival but still depends on life long immunosuppression in most patients. Current strategies employ medications that, in general, inhibit distal events mediati ...
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Journal ArticleTransplantation · November 27, 2005
BACKGROUND: Composite tissue allotransplantation (CTA) has been recently introduced as a potential treatment for tissue loss secondary to burns, injuries, or resections. However, the optimal strategies to prevent CTA rejection remain undefined. Presently, ...
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Journal ArticleTransplantation · October 27, 2005
BACKGROUND: Perioperative lymphocyte depletion induces allograft tolerance in some animal models, but in humans has only been shown to reduce immunosuppressive requirements. Without maintenance immunosuppression, depleted human renal allograft recipients e ...
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Journal ArticlePhilos Trans R Soc Lond B Biol Sci · September 29, 2005
Short-term outcomes following organ transplantation have improved considerably since the availability of cyclosporine ushered in the modern era of immunosuppression. In spite of this, many of the current limitations to progress in the field are directly re ...
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Journal ArticlePediatr Transplant · August 2005
A pediatric kidney transplant recipient receiving tacrolimus for immunosuppression experienced symptoms consistent with idiopathic intracranial hypertension. The diagnosis of idiopathic intracranial hypertension and possible secondary causes of intracrania ...
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Journal ArticleAm J Transplant · July 2005
Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are qu ...
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Journal ArticlePediatr Transplant · June 2005
By definition, tolerance will eliminate the problem of adolescent medication non-adherence. Although adolescents' propensity toward non-adherence makes them at first glance to be particularly attractive candidates for tolerance trials, there are also immun ...
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Journal ArticleAm J Transplant · May 2005
CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rod ...
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Journal ArticleJ Am Coll Surg · April 2005
BACKGROUND: Chronic allograft nephropathy (CAN) remains the leading cause of late renal allograft loss that is minimally responsive to therapy once graft dysfunction is clinically evident. A screening test capable of identifying individuals at high risk fo ...
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Journal ArticleAm J Transplant · March 2005
T-cell depletion facilitates reduced immunosuppression following organ transplantation and has been suggested to be pro-tolerant. However, the characteristics of post-depletional T cells have not been evaluated as they relate to tolerance induction. We the ...
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Journal ArticleAm J Transplant · March 2005
Renal allograft acute cellular rejection (ACR) is a T-cell mediated disease that is diagnosed histologically. However, many normally functioning allografts have T-cell infiltrates and histological ACR, and many nonimmune processes cause allograft dysfuncti ...
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Journal ArticleTranspl Int · January 2005
Immunosuppression remains the cause of most morbidity following organ transplantation. However, its use is also responsible for the outstanding graft and patient survival rates commonplace in modern transplantation. Thus, the predominant challenge for tran ...
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Chapter · 2005
The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure ...
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Journal ArticleExp Hematol · January 2005
OBJECTIVE: Activated platelets participate in inflammatory and microbicidal processes by upregulation of surface selectins, shedding of CD40 ligand, and release of platelet microbicidal proteins and microparticles. Given their myeloid lineage, we hypothesi ...
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Journal ArticleAm J Transplant · November 2004
The field of transplantation biology has, in the past year, given rise to several improved models explaining the in vivo phenomena of allograft rejection and acceptance. Although T-cells remain central participants in allorecognition, innate immune cells a ...
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Journal ArticleInt Immunol · November 2004
Blockade of the CD154-CD40 co-stimulatory pathway with anti-CD154 mAbs has shown impressive efficacy in models of autoimmunity and allotransplantation. Clinical benefit was also demonstrated in systemic lupus erythematosus (SLE) and idiopathic thrombocytop ...
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Journal ArticleKidney Int · October 2004
BACKGROUND: Organs procured from deceased donors emanate from individuals with diverse genetic backgrounds. Donor organs, therefore, may vary in their response to injury and immune stimuli in a genetically determined manner. We assessed polymorphisms from ...
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Journal ArticleExpert Opin Emerg Drugs · May 2004
Monoclonal antibodies have become valuable tools for the precise clinical manipulation of the immune system. These highly specific proteins have proven their usefulness in both the treatment and prevention of organ transplant rejection. Indeed, they are th ...
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Journal ArticleTransplantation · March 27, 2004
This article will examine internationally accepted guidelines for human experimentation as they relate to modern organ transplantation trials. Specific reference to recent clinical trials and the growing diversity of immunosuppressive protocols will be hig ...
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Journal ArticleExp Hematol · February 2004
The danger model of immunity and tolerance holds that antigen-presenting cells (APCs), activated by stress, injury, or necrosis, but not by physiological (apoptotic) cell death, initiate adaptive immune responses. APC activation is fundamentally associated ...
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Journal ArticleAm J Transplant · February 2004
Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sis ...
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Journal ArticleTranspl Immunol · 2004
Organ transplantation has become a standard life-saving therapy for many causes of end stage organ failure. Although valuable, it remains hampered by the requirement for, and complications of, immunosuppression to prevent immune rejection of the transplant ...
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Journal ArticleCurrent Opinion in Organ Transplantation · 2004
Mammalian target of rapamycin inhibitors have the potential to make a further impact in two areas. The first and most immediate possibility is through a reduction in the incidence and severity of allograft vasculopathy, with particular emphasis on heart al ...
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Journal ArticleImmunol Rev · December 2003
Many methods for reducing the immunosuppressive requirements of allotransplantation have been proposed based on a growing understanding of physiological and allospecific immunity. As these regimens are developed for clinical application, they require valid ...
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Journal ArticlePediatr Clin North Am · December 2003
Significant advances have been made in the understanding of allograft rejection. There is growing awareness that allograft acceptance, or tolerance, is also an active process rather than a passive absence of rejection. Mechanistic awareness of this process ...
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Journal ArticleAm J Transplant · November 2003
The CD154-specific monoclonal antibody (Mab) hu5c8 greatly prolongs allograft survival in primates. The CD25-specific Mab daclizumab has not, to date, been paired with hu5c8. We evaluated the effects of hu5c8 in vitro, alone and in combination with daclizu ...
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Journal ArticleFront Biosci · September 1, 2003
Molecular techniques have become a mainstay for most biomedical research. In particular, sensitive methods for gene transcript detection and advanced flow cytometry have been crucial in fostering our understanding of the basic mechanisms promoting allosens ...
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Journal ArticleAm J Transplant · August 2003
Allograft ischemia induces delayed graft function and is correlated with increasing rates of rejection. There is not currently a way to objectively measure the effects of ischemia in real-time, nor to relate therapies combating reperfusion injury with thei ...
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Journal ArticleTransplantation · July 15, 2003
BACKGROUND: We reported that rabbit anti-thymocyte globulin (RATG) induction followed by maintenance immunosuppression with sirolimus supports human kidney allograft survival and asked if this combination would promote islet allograft survival in our prima ...
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Journal ArticleTransplantation · July 15, 2003
BACKGROUND: Profound T-cell depletion before allotransplantation with gradual posttransplant T-cell repopulation induces a state of donor-specific immune hyporesponsiveness or tolerance in some animal models. Alemtuzumab (Campath-1H, Millennium Pharmaceuti ...
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Journal ArticleXenotransplantation · May 2003
Previous studies has shown that human anti-pig reactivity in mixed lymphocyte cultures require the indirect presentation of antigens by human antigen presenting cells (APC). Xenoreactivity was inhibited by blockade of human costimulatory molecules. We inve ...
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Journal ArticleJ Immunol · March 1, 2003
Anti-CD154 variably prolongs allograft survival in nonhuman primates. Rodent studies suggest that adding pretransplant donor-specific transfusion (DST) and/or rapamycin to anti-CD154 improves survival. The CD154-specific Ab IDEC-131 was tested alone and in ...
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Journal ArticleTransplantation Reviews · 2003
In summary, the results from these studies suggest that, in addition to their typical roles as antigen-processing cells serving to initiate an adaptive immune response, monocytes and macrophages may also play an effector role during rejection in patients w ...
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Journal ArticleTransplantation · December 15, 2002
BACKGROUND: Polyomavirus (PV) nephropathy has been attributed to reactivation of BK virus (BKV) or more rarely JC virus (JCV). The simian virus (SV) 40 is PV that was likely introduced into the human population through contaminated vaccines. The purpose of ...
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Journal ArticleTransplantation · November 27, 2002
BACKGROUND: Antibodies and fusion proteins specific for CD80, CD86, and CD154 have shown promise as agents capable of inducing donor-specific tolerance in rodents. These agents have also been shown to be synergistic with one another in many settings of cou ...
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Journal ArticleLancet · November 23, 2002
Renal allograft recipients generally need to take several immunosuppressive agents for life. Calcineurin inhibitors and glucocorticosteroids are the mainstays of most regimens but have undesirable chronic effects. We postulated that aggressive T-cell deple ...
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Journal ArticleTransplantation · October 15, 2002
The anti-CD154 antibody hu5C8 prevents acute allograft rejection and prolongs allograft survival after withdrawal of therapy in nonhuman primates. This study describes the use of hu5C8 as a rescue agent for rejection developing after the withdrawal of hu5C ...
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Journal ArticleTransplantation · October 15, 2002
BACKGROUND Following allotransplantation, renal ischemia-reperfusion (I/R) injury initiates a series of events that provokes counter-adaptive immunity. Though T cells clearly mediate allospecific immunity, the manner in which reperfusion events augment the ...
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Journal ArticleTranspl Infect Dis · September 2002
BACKGROUND: National statistics are presented for patient survival and graft survival in patients seropositive for the human immunodeficiency virus (HIV+) at the time of renal transplantation in the era prior to highly active antiretroviral therapy (HAART) ...
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Journal ArticleDiabetes · July 2002
We've established a nonhuman primate islet allotransplant model to address questions such as whether transplanting islets into the gut's arterial system would more safely and as effectively support long-term islet allograft survival compared with the tradi ...
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Journal ArticleAm J Transplant · July 2002
Polymorphisms in the regulatory regions of cytokine genes are associated with high and low cytokine production and may modulate the magnitude of alloimmune responses following transplantation. Ethnicity influences allograft half-life and the incidence of a ...
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Journal ArticleAm J Transplant · April 2002
A regimen combining sirolimus, tacrolimus, and daclizumab has recently been shown to provide adequate immunosuppression for allogeneic islet transplantation in humans, but remains unproven for primarily vascularized allografts. We evaluated this regimen fo ...
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Journal ArticleInorg Chem · February 25, 2002
The phosphorescence and photochemical behavior of the macrocyclic complexes (1,4,7,10,13,16-hexaazacyclooctadecane)chromium(III) (Cr([18]-aneN(6))(3+); 1) and (4,4',4''-ethylidynetris(3-azabutan-1-amine)) chromium(III) (Cr(sen)(3+); 2) have been compared t ...
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Journal ArticleClin Nephrol · January 2002
AIMS: The renin-angiotensin system (RAS) has been implicated in renal fibrosis through activation of the type I angiotensin II (Ang II) receptor (AT1R). Whether the other predominant Ang II receptor, the type 2 Ang II receptor (AT2R), has a fibrotic or spa ...
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Journal ArticleAm J Transplant · January 2002
Previous studies of the effect of donor factors on renal transplant outcomes have not tested the role of recipient body mass index, donor/recipient weight ratios and age matching, and other factors. We analyzed 20,309 adult (age 16 or older) recipients hav ...
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Journal ArticleTransplantation Reviews · 2002
Allotransplantation has improved dramatically in the past 2 decades, mostly as a result of more potent immunosuppression and increasingly effective prophylaxis against opportunistic infections. It is likely, however, that the field has entered a period of ...
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Journal ArticleTransplantation · December 15, 2001
BACKGROUND: Delayed xenograft rejection is associated with endothelial cell activation, platelet sequestration, and subsequent thrombosis. We evaluated whether human platelets could directly activate porcine endothelium (PEC), and if so, whether this was m ...
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Journal ArticleTransplantation · November 15, 2001
BACKGROUND: Allogeneic skin transplantation remains a rigorous test of any immune intervention designed to prevent allograft rejection. To date, no single, clinically available immunosuppressant has been reported to induce long-term primary skin allograft ...
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Journal ArticleTransplantation · October 27, 2001
BACKGROUND: Genetic variations in cytokine genes are thought to regulate cytokine protein production. However, studies using T cell mitogens have not always demonstrated a significant relationship between cytokine polymorphisms and in vitro protein product ...
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Journal ArticleAnn Epidemiol · October 2001
PURPOSE: To investigate the incidence, risk factors, and associated mortality of fractures in renal transplant recipients. METHODS: Retrospective registry study of 33,479 patients in the United States Renal Data System (USRDS) who received kidney transplan ...
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Journal ArticleImmunol Rev · October 2001
Non-human primate studies of tolerance induction strategies in solid organ transplantation represent a critical bridge between studies in rodents and humans. Our work demonstrates that strategies involving the blockade of co-stimulatory molecules, especial ...
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Journal ArticleTransplantation · August 27, 2001
BACKGROUND: Polymorphisms in the regulatory regions of cytokine genes affect protein production and are associated with allograft outcome. Ethnic origin has been identified as a significant prognostic factor for several immune-mediated diseases and for out ...
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Journal ArticleTransplantation · August 27, 2001
BACKGROUND: Several conventional forms of immunosuppression have been shown to antagonize the efficacy of anti-CD154 monoclonal antibody- (mAb) based costimulatory molecule blockade immunotherapy. Our objective was to determine if allograft recipients trea ...
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Journal ArticleTransplantation · August 15, 2001
CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejectio ...
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Journal ArticleAm J Transplant · July 2001
National statistics for patient characteristics and survival of renal transplant recipients positive for hepatitis C virus (HCV+) at the time of renal transplant are presented. A historical cohort analysis of 33479 renal transplant recipients in the United ...
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Journal ArticlePhilos Trans R Soc Lond B Biol Sci · May 29, 2001
CD154 plays a critical role in determining the outcome of a transplanted organ. This simple statement is amply supported by experimental evidence demonstrating that anti-CD154 antibodies are potent inhibitors of allograft rejection in many rigorous transpl ...
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Journal ArticleAm J Kidney Dis · February 2001
Rates of and risk factors for graft loss and graft loss resulting from recurrent focal segmental glomerulosclerosis (FSGS) have not been studied in a national population. A retrospective analysis was performed on a national registry (1999 United States Ren ...
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Journal ArticleAm J Nephrol · 2001
BACKGROUND: It is common belief in the transplant community that rates of septicemia in transplant recipients have declined, but this has not been studied in a national population. METHODS: Therefore, 33,479 renal transplant recipients in the United States ...
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OtherNat Med · January 2001
Migratory cells can lead to both rejection and tolerance following organ transplantation, suggesting a direction for pro-tolerant immunomodulatory therapies. ...
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Journal ArticleTransplantation · July 15, 2000
BACKGROUND: T-cell costimulatory blocking agents inhibit allospecific T-cell responses in vitro and prevent allograft rejection in vivo. Costimulatory requirements for discordant xenospecific cellular responses remain undefined. We have evaluated costimula ...
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Journal ArticleTransplantation · April 15, 2000
Genomic DNA was obtained from peripheral blood samples of patients JB and DS each of whom received a kidney transplant at 16 years of age from a serologically HLA-DR matched and HLA-class I -mismatched donor. Both patients discontinued immunosuppression af ...
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Journal ArticleTransplantation · April 15, 2000
BACKGROUND: Registry analyses and single-center studies have demonstrated that hypertension significantly increases the risk for chronic graft loss. The graft itself may contribute to posttransplant hypertension, and intragraft vasoactive hormones therefor ...
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Journal ArticleAnn Surg · March 2000
OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage ...
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Journal ArticleJ Exp Med · February 21, 2000
Signals generated through CD28-B7 and CD40 ligand (CD40L)-CD40 interactions have been shown to be crucial for the induction of long-term allograft survivability. We have recently demonstrated that humanized anti-CD40L (hu5C8) prevents rejection of mismatch ...
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Journal ArticleMicrosurgery · 2000
Clinical success has not been routinely achieved for composite tissue allotransplantation (CTA). Although most of the technical details of CTA have been overcome, the immunological aspects of these procedures have proved complex. Many traumatic conditions ...
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Journal ArticleTransplantation · November 27, 1999
BACKGROUND: Chronic rejection (CR) remains idiopathic, difficult to prospectively identify, and once detected, unresponsive to increased immunosuppression. We hypothesized that clinically stable human renal allografts have ongoing evidence of injury and im ...
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Journal ArticleJAMA · September 15, 1999
Transplantation therapies have revolutionized care for patients with endstage organ (kidney, liver, heart, lung, and pancreatic beta-cell) failure, yet significant problems persist with treatments designed to prevent graft rejection. Antirejection therapie ...
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Journal ArticleProc Natl Acad Sci U S A · July 6, 1999
Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypot ...
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Journal ArticleDiabetes · July 1999
Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and c ...
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Journal ArticleNat Med · June 1999
CD154 is the ligand for the receptor CD40. This ligand-receptor pair mediates endothelial and antigen-presenting cell activation, and facilitates the interaction of these cells with T cells and platelets. We demonstrate here that administration of a CD154- ...
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Journal ArticleTranspl Infect Dis · March 1999
The field of transplantation has developed based on two principles: allografts are rejected because they express foreign antigens, and the immune system must be suppressed to prevent rejection. Recently, in vitro and in vivo experimental evidence has accum ...
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Journal ArticleCrit Rev Immunol · 1999
Ever since the beginning of clinical transplantation, investigators have searched for a way to transplant tissues from one person to another without chronic immunosuppression. That goal, known as allograft tolerance, has remained clinically elusive. In the ...
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Journal ArticleTransplantation · July 15, 1998
BACKGROUND: FN18-CRM9 is a CD3-specific immunotoxin that is capable of depleting CD3+ T cells. Pretreatment of rhesus monkeys with this agent before transplantation can induce donor-specific tolerance and "split tolerance" to renal allografts. METHODS: Het ...
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Journal ArticleJ Pediatr Surg · January 1998
METHODS: From July 1984 to July 1995, 99 pediatric patients underwent 127 orthotopic liver transplants (OLT) at the University of Wisconsin Children's Hospital. The patients were divided into four groups according to age at time of transplant: group I, 0 t ...
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Journal ArticleTransplantation · December 27, 1997
BACKGROUND: Diastolic hypertension after renal transplantation leads to significant chronic morbidity and mortality. Recently, calcineurin phosphatase inhibition by cyclosporine or tacrolimus has been postulated to lead to diastolic hypertension through th ...
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Journal ArticleProc Natl Acad Sci U S A · August 5, 1997
Selective inhibition of T cell costimulation using the B7-specific fusion protein CTLA4-Ig has been shown to induce long-term allograft survival in rodents. Antibodies preventing the interaction between CD40 and its T cell-based ligand CD154 (CD40L) have b ...
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Journal ArticleCancer Immunol Immunother · January 1997
The human mucin, MUC-1, is a transmembrane glycoprotein that is produced by both normal an malignant epithelium. The MUC-1 produced by malignant epithelium is underglycosylated, which leads to the expression by tumors of novel T and B cell epitopes on the ...
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Journal ArticleTransplantation · December 27, 1996
BACKGROUND: Exposure to hepatitis C virus (HCV) and subsequent infection after renal transplantation lead to significant clinical hepatitis in approximately 50% of graft recipients. METHODS: One hundred thirty-two consecutive renal allotransplant patients, ...
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Journal ArticleExperimental and Clinical Endocrinology and Diabetes · 1996
After a decade of rapid development, simultaneous pancreas - kidney (SPK) transplantation has become routine at the University of Wisconsin (UW). Since developing the concept of direct drainage of pancreas allograft exocrine secretions into the urinary bla ...
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Journal ArticleHum Immunol · June 1995
Cytokine mRNA analysis was performed on human renal allograft needle core biopsies by a PCR-based assay. The assay was specifically developed to be capable of simultaneous analysis of multiple interleukin transcripts (IL-1-IL-12), as well as those of other ...
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Journal ArticleClin Transpl · 1995
After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppressio ...
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Journal ArticleTransplantation · February 1994
The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, can ...
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Journal ArticleTransplantation · October 1993
Hyperacute rejection (HAR) currently precludes the use of discordant organs for human transplantation. In order to comprehensively evaluate HAR in a clinically applicable species combination, we have developed an ex vivo perfusion model utilizing a neonata ...
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Journal ArticleTransplantation · May 1993
Hyperacute rejection is a major obstacle to successful transplantation of vascularized xenogeneic organs and is believed to be mediated at least in part by performed xenoreactive "natural antibodies" (NAb). In this study, human NAb that could be involved i ...
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Journal ArticleTransplantation · April 1993
Discordant xenogeneic transplantation offers a potentially unlimited source of donor organs from easily bred, nonendangered, physiologically compatible animals, but has been limited by the inevitable occurrence of hyperacute rejection (HAR). The potential ...
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Journal ArticleHum Immunol · January 1993
To investigate the role of gamma/delta+ T cells in allograft rejection, we have studied the TCR phenotype and function of lymphocytes infiltrating rejecting, rejected, and nonrejecting human renal allografts. Two-color immunohistologic staining showed that ...
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Journal ArticleTranspl Immunol · 1993
Donor-specific, alloreactive T cell lines may be grown from cells infiltrating human renal allografts. These T cell lines utilize restricted T cell receptor (TCR) beta-chain variable (V beta) gene repertoires, although long-term culture appears to be neces ...
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Journal ArticleTransplantation · February 1992
One-hundred consecutive human renal allograft Tru-cut needle biopsies were studied for in vitro proliferation of T lymphocytes under restrictive culture conditions containing low-dose recombinant interleukin 2. Each biopsy was entered into a blinded code a ...
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Journal ArticleArch Surg · March 1988
We encountered four cases of toothbrush swallowing and reviewed the literature on this subject. A total of 31 toothbrushes within the gastrointestinal tract have been reported. None have passed spontaneously. Several have caused significant complications r ...
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