Detrimental Effects of Donor Brain Death on Tolerance Induction May Be Eliminated by Delaying Mixed Chimerism in Non-Human Primates

Induction of tolerance in combined heart/kidney transplantation in non-human primates is possible by applying a mixed chimerism-based conditioning protocol which induces indefinite tolerance. However, donor brain death negatively impacts tolerance induction, leading to a higher incidence of humoral as well as cellular rejection. Here, we investigated whether delaying conditioning and donor bone marrow transplantation (DBMT) until four months after organ transplantation would diminish the detrimental effects of donor brain death and permit tolerance induction despite donor brain death.
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Tags: (1214) Source Type: research

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The United States Public Health Service Flag Promotion ceremony for Rear Admiral (RADM) Richard W. Childs, promoted to RADM Upper Half O-8 in January 2020, is being webcast live on 3/27/2020 from Masur Auditorium. Richard Childs, MD serves as the Clinical Director of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH). He was commissioned in the USPHS Commissioned Corps as a Lieutenant in 1995 when joined the NCI as an Oncology Fellow. Following fellowship training, he was appointed a tenure-track investigator in the Hematology Branch of the NHLBI where he continues to conduct r...
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In conclusion, taller body height at the entry to adulthood, supposed to be a marker of early-life environment, is associated with lower risk of dementia diagnosis later in life. The association persisted when adjusted for educational level and intelligence test scores in young adulthood, suggesting that height is not just acting as an indicator of cognitive reserve. A Comparison of Biological Age Measurement Approaches https://www.fightaging.org/archives/2020/02/a-comparison-of-biological-age-measurement-approaches/ Researchers here assess the performance of a range of approaches to measuring biological...
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In this study, we investigated the link between AF and senescence markers through the assessment of protein expression in the tissue lysates of human appendages from patients in AF, including paroxysmal (PAF) or permanent AF (PmAF), and in sinus rhythm (SR). The major findings of the study indicated that the progression of AF is strongly related to the human atrial senescence burden as determined by p53 and p16 expression. The stepwise increase of senescence (p53, p16), prothrombotic (TF), and proremodeling (MMP-9) markers observed in the right atrial appendages of patients in SR, PAF, and PmAF points toward multiple inter...
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Discussion Transplantation is not a common problem for primary care physicians but when a child’s disease has progressed to end-stage organ failure, transplantation can be the only treatment available. While the primary care provider usually is not involved in the daily management of patients before, during and after transplantation, they can be involved in many areas. These can include providing appropriate primary and acute care, ordering and obtaining necessary medical tests, medications and equipment, assisting with medical insurance, providing medical history and records to consultants, translating medical infor...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Since the advent of lung transplantation, chronic lung allograft dysfunction (CLAD) has been the number one cause of long-term mortality.1 A subset of T cells, known as regulatory T cells (Tregs), have been shown to suppress inflammatory responses after organ transplantation. Much of what is known about the role of Tregs in suppressing alloimmune responses has come from experimental studies of kidney, heart, pancreatic islet, liver, and bone marrow transplantation. On the basis of these findings, 2 phase I clinical trials in which adoptively transferred Tregs were administered after kidney transplantation have been completed.
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Commentary Source Type: research
In non-human primate lung transplantation, allograft acceptance has been achieved using a delayed mixed-chimerism approach consisting of 4 months of triple-drug immunosuppression (FK, MMF, steroids) followed by donor bone marrow transplantation (DBMT) along with equine-ATG, anti-IL6R mAb, anti-CD154 mAb and anti-CD8 mAb. With this protocol, 3 out of 4 monkeys accepted their grafts long-term (>299,>813,>464 days). However, anti-CD154mAb and anti-CD8 mAb are not clinically available. In kidney transplantation, persistent allograft acceptance in Cynomolgus macaques was achieved using an alternative immunosuppression ...
Source: The Journal of Heart and Lung Transplantation - Category: Transplant Surgery Authors: Source Type: research
The modern era of transplantation began in the 1954 when Dr Murray performed the first successful kidney transplant operation. Just 2 years later, Dr Thomas and colleagues performed the first successful bone marrow transplant procedure. Both physicians received the Nobel Prize in physiology or medicine in 1990 for their groundbreaking work. In the 1960s, the first liver, heart, and lung transplant procedures were performed, with most patients experiencing suboptimal outcomes. Since then, outcomes have steadily improved.
Source: Clinics in Chest Medicine - Category: Respiratory Medicine Authors: Tags: Preface Source Type: research
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by Eilon Sharon, Hao Shi, Sandhya Kharbanda, Winston Koh, Lance R. Martin, Kiran K. Khush, Hannah Valantine, Jonathan K. Pritchard, Iwijn De Vlaminck Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distr ibuted across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. Howev...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
This study is the first to show that downregulation of PAPP-A expression in adult mice can significantly extend life span. Importantly, this beneficial longevity phenotype is distinct from the dwarfism of long-lived PAPP-A KO, Ames dwarf, Snell dwarf and growth hormone receptor (GHR) KO mice with germ-line mutations. Thus, downregulation of PAPP-A expression joins other treatment regimens, such as resveratrol, rapamycin and dietary restriction, which can extend life span when started in mice as adults. In a recent study, inducible knockdown of the GHR in young adult female mice increased maximal, but not median, lif...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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