The Experts below are selected from a list of 35919 Experts worldwide ranked by ideXlab platform
Peter J Nelson - One of the best experts on this subject based on the ideXlab platform.
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a non peptide functional antagonist of the ccr1 chemokine receptor is effective in rat heart Transplant Rejection
Journal of Biological Chemistry, 2001Co-Authors: Richard Horuk, Peter J Nelson, Hermann Josef Gröne, Carol Clayberger, Alan M Krensky, Zhaohui Wang, Christian Weber, Kim S C Weber, Mary Rosser, Laura DunningAbstract:Abstract Chemokines like RANTES appear to play a role in organ Transplant Rejection. Because RANTES is a potent agonist for the chemokine receptor CCR1, we examined whether the CCR1 receptor antagonist BX471 is efficacious in a rat heterotopic heart Transplant Rejection model. Treatment of animals with BX471 and a subtherapeutic dose of cyclosporin (2.5 mg/kg), which is by itself ineffective in prolonging Transplant Rejection, is much more efficacious in prolonging Transplantation Rejection than animals treated with either cyclosporin or BX471 alone. We have examined the mechanism of action of the CCR1 antagonist in in vitro flow assays over microvascular endothelium and have discovered that the antagonist blocks the firm adhesion of monocytes triggered by RANTES on inflamed endothelium. Together, these data demonstrate a significant role for CCR1 in allograft Rejection.
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met rantes reduces vascular and tubular damage during acute renal Transplant Rejection blocking monocyte arrest and recruitment
The FASEB Journal, 1999Co-Authors: Hermann Josef Gröne, Detlef Schlondorff, Christian Weber, Kim S C Weber, Elisabeth Grone, Ton J Rabelink, Christiane Klier, Timothy N C Wells, Amanda E I Proudfoot, Peter J NelsonAbstract:Chemokines are thought to contribute to the cellular infiltrate characteristic of renal Transplant Rejection. We show that Met-RANTES, a chemokine receptor antagonist, suppresses recruitment of inflammatory cells into renal allografts. In a renal Transplant model (Fisher RT1lvl rat kidney into Lewis RT1l rat) where no additional immune suppressant was used, Met-RANTES-treated animals showed a significant reduction in vascular injury score (16.10 ± 5.20 vs. 62.67 ± 18.64) and tubular damage score (15.70 ± 5.22 vs. 33.00 ± 6.44) relative to untreated animals. In a more severe Rejection model (Brown-Norway RT1n rat kidney into Lewis RT11 rat), Met-RANTES significantly augmented low-dose cyclosporin A treatment to reduce all aspects of renal injury including interstitial inflammation (score 71.00 ± 6.10 vs. 157.30 ± 21.30). The majority of infiltrating cells in these models (60–70%) consisted of monocytes. Potential mechanisms of action of Met-RANTES were tested using monocyte attachment assays on microvascul...
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rantes chemokine expression in cell mediated Transplant Rejection of the kidney
The Lancet, 1994Co-Authors: James M Pattison, Peter J Nelson, Alan M Krensky, I Von Leuttichau, Philip Huie, G Farshid, Richard K SibleyAbstract:: RANTES (regulated upon activation, normal T cell expressed and secreted) is a chemotactic cytokine (a chemokine) for memory T lymphocytes, monocytes, and eosinophils. RANTES expression was studied in renal allograft biopsy specimens. Although RANTES was not expressed in samples taken one hour after Transplantation, or in native renal biopsy specimens from patients with cyclosporin nephrotoxicity, it was expressed during cell-mediated Transplant Rejection. RANTES mRNA was detected in infiltrating mononuclear cells and renal tubular epithelium, and RANTES protein was localised to mononuclear cells, tubular epithelium, and vascular endothelium. This suggests RANTES has a role in allograft Rejection.
Tara K Sigdel - One of the best experts on this subject based on the ideXlab platform.
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advances in diagnostics for Transplant Rejection
Expert Review of Molecular Diagnostics, 2016Co-Authors: Michael Nasr, Tara K Sigdel, Minnie M SarwalAbstract:ABSTRACTIntroduction: Identification of allograft injury, including acute clinical and subclinical injury, is vital in increasing the longevity of the Transplanted organ. Acute Rejection, which occurs as a result of a variety of immune and non-immune factors including the infiltration of immune cells and antibodies to the donor specific epitopes, poses a significant risk to the organ. Recent years have marked an increase in the discovery of new genomic, transcriptomic, and proteomic biomarkers in molecular diagnostics, which offer better potential for personalized management of the Transplanted organ by providing earlier detection of Rejection episodes.Areas covered: This review was compiled from key word searches of full-text publications relevant to the field.Expert commentary: Many of the recent advancements in the molecular diagnostics of allograft injury show much promise, but before they can be fully realized further validation in larger sample sets must be conducted. Additionally, for better inform...
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identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft Rejection
PLOS ONE, 2013Co-Authors: Kiran K Khush, Tara K Sigdel, Szuchuan Hsieh, Lihua Ying, Helen Luikart, Silke Roedder, Andrew C YangAbstract:To test, whether 10 genes, diagnostic of renal allograft Rejection in blood, are able to diagnose and predict cardiac allograft Rejection, we analyzed 250 blood samples from heart Transplant recipients with and without acute Rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of Rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ Transplant Rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal Transplant Rejection, can be utilized serially after cardiac Transplantation, to diagnose and predict biopsy confirmed acute heart Transplant Rejection.
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shotgun proteomics identifies proteins specific for acute renal Transplant Rejection
Proteomics Clinical Applications, 2010Co-Authors: Tara K Sigdel, Amit Kaushal, Marina A Gritsenko, Angela D Norbeck, Weijun Qian, Wenzhong Xiao, David G Camp, Richard D Smith, Minnie M SarwalAbstract:Acute Rejection (AR) remains the primary risk factor for renal Transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics applying LC-MS/MS and ELISA to analyze a set of 92urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal Transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft Rejection after kidney Transplantation.
Roy S Gardner - One of the best experts on this subject based on the ideXlab platform.
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ferumoxytol enhanced mri in patients with prior cardiac Transplantation
Open heart, 2019Co-Authors: Colin Stirrat, Shirjel Alam, Tom Macgillivray, Calum Gray, Marc R Dweck, Victor Jones, W H B Wallace, John R Payne, Sanjay K Prasad, Roy S GardnerAbstract:Objectives Ultra-small superparamagnetic particles of iron oxide (USPIO)-enhanced MRI can detect cellular inflammation within tissues and may help non-invasively identify cardiac Transplant Rejection. Here, we aimed to determine the normal reference values for USPIO-enhanced MRI in patients with a prior cardiac Transplant and examine whether USPIO-enhanced MRI could detect myocardial inflammation in patients with Transplant Rejection. Methods Ten volunteers and 11 patients with cardiac Transplant underwent T2, T2* and late gadolinium enhancement 1.5T MRI, with further T2* imaging at 24 hours after USPIO (ferumoxytol, 4 mg/kg) infusion, at baseline and 3 months. Results Ten patients with clinically stable cardiac Transplantation were retained for analysis. Myocardial T2 values were higher in patients with cardiac Transplant versus healthy volunteers (53.8±5.2 vs 48.6±1.9 ms, respectively; p=0.003). There were no differences in the magnitude of USPIO-induced change in R2* in patients with Transplantation (change in R2*, 26.6±7.3 vs 22.0±10.4 s-1 in healthy volunteers; p=0.28). After 3 months, patients with Transplantation (n=5) had unaltered T2 values (52.7±2.8 vs 52.12±3.4 ms; p=0.80) and changes in R2* following USPIO (29.42±8.14 vs 25.8±7.8 s-1; p=0.43). Conclusion Stable patients with cardiac Transplantation have increased myocardial T2 values, consistent with resting myocardial oedema or fibrosis. In contrast, USPIO-enhanced MRI is normal and stable over time suggesting the absence of chronic macrophage-driven cellular inflammation. It remains to be determined whether USPIO-enhanced MRI may be able to identify acute cardiac Transplant Rejection. Trial registration number NCT02319278349 (https://clinicaltrials.gov/ct2/show/NCT02319278) Registered 03.12.2014 EUDraCT 2013-002336-24.
Simon R Knight - One of the best experts on this subject based on the ideXlab platform.
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a systematic review of the use of rituximab for the treatment of antibody mediated renal Transplant Rejection
Transplantation Reviews, 2017Co-Authors: Philip S Macklin, Peter J Morris, Simon R KnightAbstract:Rituximab is a B-lymphocyte depleting agent that is used to treat hematological malignancies and autoimmune diseases. Recently, it has gained interest as an immunomodulatory agent in renal Transplantation. This systematic review evaluates the evidence for its use in the treatment of acute and chronic antibody-mediated renal Transplant Rejection (AAMR; CAMR). A systematic search of four databases and three trial registries was conducted. The small number and heterogeneous nature of included studies precluded meta-analysis and thus a narrative review was conducted. A total of 28 records met the inclusion criteria (AAMR, 18 records relating to 9 studies; CAMR, 10 records relating to 7 studies). Two systematic reviews were identified that had differing inclusion criteria to this current review. Of seven primary studies in the setting of AAMR, four reported increased graft survival and one reported improved graft function with rituximab. This contrasts with CAMR in which only one of seven studies reported improved graft outcomes with a rituximab-based regimen; three studies reported inferior outcomes and three reported no difference. Only one study reported that rituximab was associated with an increase in adverse effects. The included studies suggest that rituximab may be of some benefit in the setting of AAMR but a lack of high quality evidence precludes firm conclusions from being drawn. Rituximab does not appear to reliably improve outcomes in CAMR. Further well-conducted studies are required to better define the effects and long-term safety profile of rituximab in the treatment of antibody-mediated renal Transplant Rejection.
Gerhard Opelz - One of the best experts on this subject based on the ideXlab platform.
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antibodies against mica antigens and kidney Transplant Rejection
The New England Journal of Medicine, 2007Co-Authors: Peter Stastny, Caner Süsal, Bernd Dohler, Gerhard OpelzAbstract:Background Good HLA-A, HLA-B, and HLA-DR matches do not guarantee Rejection-free renal Transplantation. Some kidney Transplants fail despite such matches, suggesting that other antigens might be targets for Rejection. Major-histocompatibility-complex (MHC) class I–related chain A (MICA) antigens are polymorphic and can elicit antibody production. We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts. Methods PreTransplantation serum samples from 1910 recipients of kidney Transplants from deceased donors were tested for anti-MICA antibodies with an assay in which single MICA antigens were attached to polystyrene microspheres. Results Antibodies against MICA alleles were detected in 217 of the 1910 patients (11.4%). The presence of MICA antibodies was associated with renal-allograft Rejection. The mean (±SE) 1-year graft-survival rate was 88.3±2.2% among recipients with anti-MICA antibodies as compared with 93.0±0.6% among recipients without...
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antibodies against mica antigens and kidney Transplant Rejection
The New England Journal of Medicine, 2007Co-Authors: Peter Stastny, Caner Süsal, Bernd Dohler, Gerhard OpelzAbstract:Background Good HLA-A, HLA-B, and HLA-DR matches do not guarantee Rejection-free renal Transplantation. Some kidney Transplants fail despite such matches, suggesting that other antigens might be targets for Rejection. Major-histocompatibility-complex (MHC) class I–related chain A (MICA) antigens are polymorphic and can elicit antibody production. We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts. Methods PreTransplantation serum samples from 1910 recipients of kidney Transplants from deceased donors were tested for anti-MICA antibodies with an assay in which single MICA antigens were attached to polystyrene microspheres. Results Antibodies against MICA alleles were detected in 217 of the 1910 patients (11.4%). The presence of MICA antibodies was associated with renal-allograft Rejection. The mean (±SE) 1-year graft-survival rate was 88.3±2.2% among recipients with anti-MICA antibodies as compared with 93.0±0.6% among recipients without...