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Rejection sensitivity

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https://www.readbyqxmd.com/read/28207630/clinical-trials-for-immunosuppression-in-transplantation-the-case-for-reform-and-change-in-direction
#1
Philip J O'Connell, Dirk Kuypers, Roslyn R Mannon, Michael Abecassis, Stephen Chadban, John S Gill, Barbara Murphy, Peter W Nickerson, Jesse D Schold, Peter Stock, Daniel Seron, Rita Alloway, Jonathan Bromberg, Klemens Budde, Stanley Jordan, Christophe Legendre, Carmen Lefaucheur, Minnie Sarwall, Dorry Segev, Mark D Stegall, Stefan G Tullius, Germaine Wong, E Steve Woodle, Nancy Ascher, Randall E Morris
Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared to current standard of care. Current trial design is not leading to novel therapies improving long term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28203294/correlation-between-nad-p-h-quinone-oxidoreductase-1-c609t-polymorphism-and-increased-risk-of-esophageal-cancer-evidence-from-a-meta-analysis
#2
Jingfang Diao, Jie Bao, Jianxin Peng, Jiaqiang Mo, Qing Ye, Junming He
NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphisms have been reported to influence the risk for esophageal cancer (EC) in many studies. However, the results remain controversial and ambiguous. We performed a meta-analysis, which included 13 independent studies with a total of 2357 subjects, to examine the association between NQO1 C609T polymorphism and EC. The association was assessed by five different gene models. The overall analysis suggested that the variant allele and genotypes were significantly related to increased risk of EC (odds ratio [OR] T versus C = 1...
January 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28201989/revisiting-phylogenetic-signal-strong-or-negligible-impacts-of-polytomies-and-branch-length-information
#3
Rafael Molina-Venegas, Miguel Á Rodríguez
BACKGROUND: Inaccurate estimates of phylogenetic signal may mislead interpretations of many ecological and evolutionary processes, and hence understanding where potential sources of uncertainty may lay has become a priority for comparative studies. Importantly, the sensitivity of phylogenetic signal indices and their associated statistical tests to incompletely resolved phylogenies and suboptimal branch-length information has been only partially investigated. METHODS: Here, we use simulations of trait evolution along phylogenetic trees to assess whether incompletely resolved phylogenies (polytomic chronograms) and phylogenies with suboptimal branch-length information (pseudo-chronograms) could produce directional biases in significance tests (p-values) associated with Blomberg et al...
February 15, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28199785/assessment-of-tocilizumab-anti-il-6-receptor-monoclonal-as-a-potential-treatment-for-chronic-antibody-mediated-rejection-and-transplant-glomerulopathy-in-hla-sensitized-renal-allograft-recipients
#4
Jua Choi, Olivier Aubert, Ashley Vo, Alexandre Loupy, Mark Haas, Dechu Puliyanda, Irene Kim, Sabrina Louie, Alexis Kang, Alice Peng, Joe Kahwaji, Nancy Reinsmoen, Mieko Toyoda, Stanley C Jordan
Extending the functional integrity of renal allografts is the primary goal of transplant medicine. Development of donor-specific antibodies (DSAs) post-transplant leads to chronic active antibody-mediated rejection (cABMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses in the U.S. This reduces the quality & length of life for patients and increases cost. There are no approved treatments for cABMR. Evidence suggests the pro-inflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cABMR...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28194745/understanding-approach-and-avoidance-in-verbal-descriptions-of-everyday-actions-an-erp-study
#5
Hipólito Marrero, Mabel Urrutia, David Beltrán, Elena Gámez, José M Díaz
Understanding verbal descriptions of everyday actions could involve the neural representation of action direction (avoidance and approach) toward persons and things. We recorded the electrophysiological activity of participants while they were reading approach/avoidance action sentences that were directed toward a target: a thing/a person (i.e., "Petra accepted/rejected Ramón in her group"/ "Petra accepted/rejected the receipt of the bank"). We measured brain potentials time locked to the target word. In the case of things, we found a N400-like component with right frontal distribution modulated by approach/avoidance action...
February 13, 2017: Cognitive, Affective & Behavioral Neuroscience
https://www.readbyqxmd.com/read/28193698/the-innate-and-adaptive-infiltrating-immune-systems-as-targets-for-breast-cancer-immunotherapy
#6
Andrew Mk Law, Elgene Lim, Christopher Ormandy, David Gallego-Ortega
A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis, and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy...
February 13, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28193069/comprehensive-metabolite-identification-strategy-using-multiple-two-dimensional-nmr-spectra-of-a-complex-mixture-implemented-in-the-colmarm-web-server
#7
Kerem Bingol, Da-Wei Li, Bo Zhang, Rafael Brüschweiler
Identification of metabolites in complex mixtures represents a key step in metabolomics. A new strategy is introduced, which is implemented in a new public web server, COLMARm, that permits the coanalysis of up to three two-dimensional (2D) NMR spectra, namely, (13)C-(1)H HSQC (heteronuclear single quantum coherence spectroscopy), (1)H-(1)H TOCSY (total correlation spectroscopy), and (13)C-(1)H HSQC-TOCSY, for the comprehensive, accurate, and efficient performance of this task. The highly versatile and interactive nature of COLMARm permits its application to a wide range of metabolomics samples independent of the magnetic field...
December 20, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/28191531/urine-biomarkers-in-renal-allograft
#8
Hongting Wang, Zuan-Tao Lin, Yulin Yuan, Tianfu Wu
There is a high risk for the survival of patients with an end-stage renal disease for kidney transplantation. To avoid rejection by strict medication adherence is of utmost importance to avoid the failure of a kidney transplant. It is imperative to develop non-invasive biomarkers to assess immunity risk, and to ultimately provide guidance for therapeutic decision-making following kidney transplantation. Urine biomarkers may represent the promising non-invasive tools that will help in predicting risk or success rates of kidney transplantations...
September 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28191005/significance-of-anti-hla-antibodies-on-adult-and-pediatric-heart-allograft-outcomes
#9
REVIEW
Massimo Mangiola, Marilyn Marrari, Brian Feingold, Adriana Zeevi
As methods for human leukocyte antigens (HLA) antibody detection have evolved and newer solid phase assays are much more sensitive, the last 15 years has seen a renewed focus on the importance of HLA antibodies in solid organ transplant rejection. However, there is still much controversy regarding the clinical significance of antibody level as depicted by the mean fluorescence intensity of a patient's neat serum. Emerging techniques, including those that identify antibody level and function, show promise for the detection of individuals at risk of allograft rejection, determination of the effectiveness of desensitization prior to transplant, and for monitoring treatment of rejection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28185259/ips-cell-derived-gamete-associated-proteins-gaps-incite-rejection-of-ipscs-in-syngeneic-mice
#10
Eun-Mi Kim, Gohar Manzar, Nicholas Zavazava
The safety of iPS cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not ES cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesized that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection...
February 10, 2017: Immunology
https://www.readbyqxmd.com/read/28179732/a-microfabricated-optically-pumped-magnetic-gradiometer
#11
D Sheng, A R Perry, S P Krzyzewski, S Geller, J Kitching, S Knappe
We report on the development of a microfabricated atomic magnetic gradiometer based on optical spectroscopy of alkali atoms in the vapor phase. The gradiometer, which operates in the spin-exchange relaxation free regime, has a length of 60 mm and cross sectional diameter of 12 mm, and consists of two chip-scale atomic magnetometers which are interrogated by a common laser light. The sensor can measure differences in magnetic fields, over a 20 mm baseline, of 10 fT/[Formula: see text] at frequencies above 20 Hz...
January 16, 2017: Applied Physics Letters
https://www.readbyqxmd.com/read/28174628/misleading-bilateral-blink-reflex-loss-in-a-severe-tetanus-case
#12
Bernhard Neumann, Wilhelm Schulte-Mattler, Kornelius Fuchs, Ruth Zellner, Sandra Boy, Klemens Angstwurm
Tetanus is rare and often forgotten in the diagnostic workup. The diagnosis is mainly based on typical clinical symptoms, because of missing sensitive paraclinical test. As described in our case, a missing bilateral blink reflex may occur in severe tetanus, which should not lead to the rejection of the diagnosis.
February 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28165247/highly-narrowband-photomultiplication-type-organic-photodetectors
#13
Wenbin Wang, Fujun Zhang, Mingde Du, Lingliang Li, Miao Zhang, Kai Wang, Yongsheng Wang, Bin Hu, Ying Fang, Jinsong Huang
Filterless narrowband response organic photodetectors (OPDs) present a great challenge due to the broad absorption range of organic semiconducting materials. The reported narrowband response OPDs also suffer from low external quantum efficiency (EQE) in the desired response window and low rejection ratio. Here, we report highly narrowband photomultiplication (PM) type OPDs based on P3HT:PC71BM (100:1, wt/wt) as active layer without an optical filter. The full-width at half-maximum (FWHM) of the PM type OPDs can be well retained less than 30 nm under different biases...
February 6, 2017: Nano Letters
https://www.readbyqxmd.com/read/28162932/multicenter-evaluation-of-a-national-organ-sharing-policy-for-highly-sensitized-patients-listed-for-heart-transplantation-in-canada
#14
Brian Clarke, Anique Ducharme, Nadia Giannetti, Daniel Kim, Michael McDonald, Peter Pflugfelder, Miroslaw Rajda, Mario Sénéchal, Ellie Stadnick, Mustafa Toma, Shelley Zieroth, Debra Isaac
BACKGROUND: Transplantation of sensitized recipients has been associated with increased risk of post-transplant complications. In 2010, the Canadian Cardiac Transplant Network (CCTN) created a unique status listing for highly sensitized heart transplant candidates. Status 4S listing requires calculated panel-reactive antibody (cPRA) level >80% as the sole listing criteria and enables geographic expansion of the donor pool by providing national access. In this study, we describe patient characteristics and outcomes of those transplanted as Status 4S in Canada...
January 6, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28159313/a-pi-tuning-rule-for-integrating-plus-dead-time-processes-with-parametric-uncertainty
#15
Pedro Mercader, Alfonso Baños
A novel method to tune a Proportional-Integral (PI) compensator for an integrating plus dead time (IPDT) process, in presence of interval parametric uncertainty, is presented. The design is based on optimization of load disturbance rejection with constraints on the magnitude of the sensitivity and complementary sensitivity functions, that must be satisfied for any element belonging to a set of plants. Instead of solving this problem with a brute force approach (grid the uncertainty set), we prove that this problem can be solved by considering only two plants...
January 31, 2017: ISA Transactions
https://www.readbyqxmd.com/read/28151807/the-impact-of-antibodies-and-virtual-crossmatching-on-intestinal-transplant-outcomes
#16
Elaine Y Cheng, Bernard J DuBray, Douglas G Farmer
PURPOSE OF REVIEW: Sensitization to human leukocyte antigens (HLAs) limits access to potential donors and contributes to inferior graft survival after transplantation. In this article, we will review the effects of HLA-specific antibodies on intestinal transplant outcomes, and discuss considerations in the monitoring and treatment of anti-HLA antibodies. RECENT FINDINGS: Only a handful of studies has investigated the effects of donor-specific anti-HLA antibodies (DSAs) on intestinal allograft outcomes...
February 1, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28147232/use-of-ubiquitous-highly-heterozygous-copy-number-variants-and-digital-droplet-pcr-to-monitor-chimerism-after-allogeneic-haematopoietic-stem-cell-transplantation
#17
John B Whitlam, Ling Ling, Michael Swain, Tom Harrington, Oksana Mirochnik, Ian Brooks, Sara Cronin, Jackie Challis, Vida Petrovic, Damien L Bruno, Francoise Mechinaud, Rachel Conyers, Howard Slater
Chimerism analysis has an important role in the management of allogeneic haematopoietic stem cell transplantation. It informs response to disease relapse, graft rejection and graft-versus-host disease. We have developed a method for chimerism analysis using ubiquitous copy number variation (CNV), which has the benefit of a "negative background" against which multiple independent informative markers are absolutely quantified using digital droplet PCR. A panel of up to 38 CNV markers with homozygous deletion frequencies of approximately 0...
January 29, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28142500/hyaluronic-acid-collagen-hydrogel-as-an-alternative-to-alginate-for-long-term-immunoprotected-islet-transplantation
#18
Stephen Harrington, S Janette Williams, Sonia Rawal, Karthik Ramachandran, Lisa Stehno-Bittel
Alginate has long been the material of choice for immunoprotection of islets for its low cost and ability to easily form microspheres. Unfortunately, this seaweed-derived material is notoriously prone to fibrotic overgrowth in vivo, resulting in premature graft failure. The purpose of this study was to test an alternative, hyaluronic acid (HA-COL), for in vitro function, viability and allogeneic islet transplant outcomes in diabetic rats. In vitro studies indicated that the HA-COL gel had diffusion characteristics that would allow small molecules like glucose and insulin to enter and exit the gel, while larger molecules (70 and 500kD dextrans) were impeded from diffusing past the gel edge in 24 hours...
January 31, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28135788/corticosteroid-wean-after-heart-transplantation-is-there-a-risk-for-antibody-formation
#19
Omeed Elboudwarej, Derek Phan, Jignesh K Patel, Frank Liou, Tamar Aintablian, Ashley Osborne, Zhe Yu, Nancy Reinsmoen, Jon A Kobashigawa
BACKGROUND: Corticosteroid withdrawal after heart transplantation is limited to select immune-privileged patients but it is not known whether this predisposes patients to a higher risk for sensitization. METHODS: A total of 178 heart transplant recipients had panel-reactive antibody (PRA) measurements at transplant and every 6 months and were monitored for rejection with protocol endomyocardial biopsies. Corticosteroid withdrawal was initiated at 6 months post-transplant in select patients...
January 30, 2017: Clinical Transplantation
https://www.readbyqxmd.com/read/28133934/a-novel-immune-function-biomarker-identifies-patients-at-risk-of-clinical-events-early-following-liver-transplantation
#20
Siddharth Sood, Craig Haifer, Lijia Yu, Julie Pavlovic, Leonid Churilov, Paul J Gow, Robert M Jones, Peter W Angus, Kumar Visvanathan, Adam G Testro
: Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon gamma (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. 75 adult transplant recipients were prospectively monitored in a blinded, observational study. 55/75 (73.3%) patients experienced a total 89 clinical events...
January 30, 2017: Liver Transplantation
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