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tolerance in transplantation

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https://www.readbyqxmd.com/read/28210263/a-paradigm-shift-on-the-question-of-b-cells-in-transplantation-recent-insights-on-regulating-the-alloresponse
#1
REVIEW
Daniel J Firl, Gilles Benichou, James I Kim, Heidi Yeh
B lymphocytes contribute to acute and chronic allograft rejection through their production of donor-specific antibodies (DSAs). In addition, B cells present allopeptides bound to self-MHC class II molecules and provide costimulation signals to T cells, which are essential to their activation and differentiation into memory T cells. On the other hand, both in laboratory rodents and patients, the concept of effector T cell regulation by B cells is gaining traction in the field of transplantation. Specifically, clinical trials using anti-CD20 monoclonal antibodies to deplete B cells and reverse DSA had a deleterious effect on rates of acute cellular rejection; a peculiar finding that calls into question a central paradigm in transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#2
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207630/clinical-trials-for-immunosuppression-in-transplantation-the-case-for-reform-and-change-in-direction
#3
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/28202353/the-potential-clinical-promise-of-multimodality-metronomic-chemotherapy-revealed-by-preclinical-studies-of-metastatic-disease
#4
Robert S Kerbel, Yuval Shaked
We present a rationale for further clinical development and assessment of metronomic chemotherapy on the basis of unexpected results obtained in translational mouse models of cancer involving treatment of advanced metastatic disease. Historically, mouse cancer therapy models have been dominated by treating established primary tumors or early stage low volume microscopic disease. Treatment of primary tumors is also almost always the case when using genetically engineered mouse models (GEMMS) of cancer or patient-derived xenografts (PDXs)...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199304/adipose-derived-circulating-mirnas-regulate-gene-expression-in-other-tissues
#5
Thomas Thomou, Marcelo A Mori, Jonathan M Dreyfuss, Masahiro Konishi, Masaji Sakaguchi, Christian Wolfrum, Tata Nageswara Rao, Jonathon N Winnay, Ruben Garcia-Martin, Steven K Grinspoon, Phillip Gorden, C Ronald Kahn
Adipose tissue is a major site of energy storage and has a role in the regulation of metabolism through the release of adipokines. Here we show that mice with an adipose-tissue-specific knockout of the microRNA (miRNA)-processing enzyme Dicer (ADicerKO), as well as humans with lipodystrophy, exhibit a substantial decrease in levels of circulating exosomal miRNAs. Transplantation of both white and brown adipose tissue-brown especially-into ADicerKO mice restores the level of numerous circulating miRNAs that are associated with an improvement in glucose tolerance and a reduction in hepatic Fgf21 mRNA and circulating FGF21...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#6
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4(+) and CD8(+) Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4(+) and CD8(+) Foxp3(+) Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193829/soluble-cd83-inhibits-t-cell-activation-by-binding-to-the-tlr4-md-2-complex-on-cd14-monocytes
#7
Joe M Horvatinovich, Elizabeth W Grogan, Marcus Norris, Alexander Steinkasserer, Henrique Lemos, Andrew L Mellor, Irina Y Tcherepanova, Charles A Nicolette, Mark A DeBenedette
The transmembrane protein CD83, expressed on APCs, B cells, and T cells, can be expressed as a soluble form generated by alternative splice variants and/or by shedding. Soluble CD83 (sCD83) was shown to be involved in negatively regulating the immune response. sCD83 inhibits T cell proliferation in vitro, supports allograft survival in vivo, prevents corneal transplant rejection, and attenuates the progression and severity of autoimmune diseases and experimental colitis. Although sCD83 binds to human PBMCs, the specific molecules that bind sCD83 have not been identified...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28191009/defective-il-23-il-17-axis-protects-p47phox-mice-from-colon-cancer
#8
Cornelia Richter, Martina Herrero San Juan, Benno Weigmann, Dominik Bergis, Katrin Dauber, Michael H Muders, Gustavo B Baretton, Josef Martin Pfeilschifter, Halvard Bonig, Sebastian Brenner, Heinfried H Radeke
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188592/redirecting-reproductive-immunology-research-toward-pregnancy-as-a-period-of-temporary-immune-tolerance
#9
Norbert Gleicher, Vitaly A Kushnir, David H Barad
Referring to two recent publications, we here propose that clinical reproductive immunology has for decades stagnated because reproductive medicine, including assisted reproduction (AR), has failed to accept embryo implantation as an immune system-driven process, dependent on establishment of maternal tolerance toward the implanting fetal semi-allograft (and complete allograft in cases of oocyte donation). Pregnancy represents a biologically unique period of temporary (to the period of gestation restricted) tolerance, otherwise only known in association with parasitic infections...
February 10, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28187014/delayed-donor-bone-marrow-infusion-induces-liver-transplant-tolerance
#10
Yan Xie, Yang Wu, Kang Xin, Jiao-Jing Wang, Hong Xu, Suzanne T Ildstad, Joseph Leventhal, Guang-Yu Yang, Zheng Zhang, Josh Levitsky
BACKGROUND: Nonmyeloablative conditioning followed by donor bone marrow infusion (BMI) to induce tolerance has not been robustly tested in liver transplantation (LT) and may be unsafe at the time of LT. We hypothesized T cell depleted BMI is effective in inducing tolerance when delayed after LT, resulting in potentially safer future clinical applications. METHODS: Nonimmunosuppressed syngeneic (Lewis to Lewis) and allogeneic (ACI to Lewis) rat LT transplants were initially performed as controls...
February 10, 2017: Transplantation
https://www.readbyqxmd.com/read/28186707/mesenchymal-stromal-cell-therapy-for-chronic-lung-allograft-dysfunction-results-of-a-first-in-man-study
#11
Daniel C Chambers, Debra Enever, Sharon Lawrence, Marian J Sturm, Richard Herrmann, Stephanie Yerkovich, Michael Musk, Peter M A Hopkins
Chronic lung transplant rejection (termed chronic lung allograft dysfunction [CLAD]) is the main impediment to long-term survival after lung transplantation. Bone marrow-derived mesenchymal stromal cells (MSCs) represent an attractive cell therapy in inflammatory diseases, including organ rejection, given their relative immune privilege and immunosuppressive and tolerogenic properties. Preclinical studies in models of obliterative bronchiolitis and human trials in graft versus host disease and renal transplantation suggest potential efficacy in CLAD...
February 1, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28186132/bacterial-community-dynamics-are-linked-to-patterns-of-coral-heat-tolerance
#12
Maren Ziegler, Francois O Seneca, Lauren K Yum, Stephen R Palumbi, Christian R Voolstra
Ocean warming threatens corals and the coral reef ecosystem. Nevertheless, corals can be adapted to their thermal environment and inherit heat tolerance across generations. In addition, the diverse microbes that associate with corals have the capacity for more rapid change, potentially aiding the adaptation of long-lived corals. Here, we show that the microbiome of reef corals is different across thermally variable habitats and changes over time when corals are reciprocally transplanted. Exposing these corals to thermal bleaching conditions changes the microbiome for heat-sensitive corals, but not for heat-tolerant corals growing in habitats with natural high heat extremes...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28185203/hla-haploidentical-hematopoietic-cell-transplantation-using-clofarabine-and-busulfan-for-refractory-pediatric-hematological-malignancy
#13
Masatoshi Takagi, Yasuyoshi Ishiwata, Yuki Aoki, Satoshi Miyamoto, Akihiro Hoshino, Kazuaki Matsumoto, Akira Nishimura, Mari Tanaka, Masakatsu Yanagimachi, Noriko Mitsuiki, Kohsuke Imai, Hirokazu Kanegane, Michiko Kajiwara, Kanako Takikawa, Tsukasa Mae, Osamu Tomita, Junya Fujimura, Masato Yasuhara, Daisuke Tomizawa, Shuki Mizutani, Tomohiro Morio
Haploidentical hematopoietic cell transplantation (HCT) conditioning with clofarabine and target area under the blood concentration-time curve (AUC)-based busulfan adjustment was performed in three patients with refractory pediatric leukemia. The target AUC for two patients who had already received multiple transplantations was 3600 and 4000 μmol min/L, and that for the patient with Down's syndrome was 3000 μmol min/L. Regimen-related toxicity was well tolerated in all cases. All three maintained cytological remission throughout the follow-up period (between 31 and 167 weeks)...
February 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28178174/real-world-experience-with-interferon-free-direct-acting-antiviral-therapies-in-asian-americans-with-chronic-hepatitis-c-and-advanced-liver-disease
#14
Christine Y Chang, Pauline Nguyen, An Le, Changqing Zhao, Aijaz Ahmed, Tami Daugherty, Gabriel Garcia, Glen Lutchman, Radhika Kumari, Mindie H Nguyen
Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans.To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies.This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28178089/hepatitis-c-virus-therapy-for-decompensated-and-posttransplant-patients
#15
Francis Dailey, Walid S Ayoub
Treatment of hepatitis C (HCV) has been revolutionized with the introduction of the direct-acting antivirals (DAA). The DAAs allowed patients to better tolerate HCV therapy with much lower side effects and better efficacy. The DAA also offered hope for a cure in HCV patients who cannot tolerate interferon-based therapy. Such populations include patients with decompensated cirrhosis and postliver transplantation. Despite DAA therapy showing cure rate of over 95% in the absence of cirrhosis, cure rate in the decompensated liver disease setting remains lower...
March 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28178052/fecal-microbiota-transplant-for-clostridium-difficile-infection-in-a-pregnant-patient
#16
Bejan J Saeedi, Doree Gardner Morison, Colleen S Kraft, Tanvi Dhere
BACKGROUND: Clostridium difficile infection has been associated with negative outcomes in the general population and in pregnant patients. Fecal microbiota transplant has become the standard for treatment of recurrent as well as refractory C difficile infection. CASE: We present a case of a 28-year-old pregnant woman who presented with recurrent C difficile infection despite treatment with vancomycin and fidaxomicin and underwent a successful fecal microbiota transplant through colonoscopy at 18 weeks of gestation...
February 6, 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28177199/daclatasvir-plus-sofosbuvir-with-or-without-ribavirin-for-hepatitis-c-virus-genotype-3-in-a-french-early-access-programme
#17
Christophe Hézode, Pascal Lebray, Victor De Ledinghen, Fabien Zoulim, Vincent Di Martino, Nathalie Boyer, Dominique Larrey, Danielle Botta-Fridlund, Christine Silvain, Hélène Fontaine, Louis D'Alteroche, Vincent Leroy, Marc Bourliere, Isabelle Hubert-Fouchard, Dominique Guyader, Isabelle Rosa, Eric Nguyen-Khac, Larysa Fedchuk, Raoudha Akremi, Yacia Bennai, Anne Filipovics, Yue Zhao, Jean-Pierre Bronowicki
BACKGROUND AND AIMS: Optimally effective treatment for hepatitis C virus (HCV) genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir (DCV) plus sofosbuvir (SOF) was efficacious in phase 3 studies. Real-world data for DCV+SOF in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to DCV ahead of its market authorization. METHODS: Patients with F3/F4 fibrosis and/or extrahepatic HCV manifestations, post-liver-transplant HCV recurrence, and/or indication for liver/kidney transplant, were treated with DCV+SOF (60+400 mg daily) for a recommended duration of 24 weeks...
February 8, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28176896/paclitaxel-loaded-hyaluronan-solid-nanoemulsions-for-enhanced-treatment-efficacy-in-ovarian-cancer
#18
Joo-Eun Kim, Young-Joon Park
Paclitaxel-loaded hyaluronan solid nanoemulsions (PTX-HSNs) were successfully fabricated for the delivery of PTX to improve ovarian cancer treatment via active tumor targeting. PTX-HSNs were fabricated using high-pressure homogenization with a microfluidizer and were lyophilized with d-mannitol. Hyaluronan was coated on the outside of the PTX-HSN sphere. The mean size of the PTX-HSNs was maintained less than 100 nm, with a relatively narrow size distribution. The PTX loading content was 3 mg/mL, and encapsulation efficiency (EE) was close to 100%...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28174390/-surgical-regeneration-therapy-using-myoblast-sheets-for-severe-heart-failure
#19
Yoshiki Sawa
Heart failure is a life-threatening disorder worldwide, and the current end-stage therapies for severe heart failure are replacement therapies such as ventricular-assist devices and heart transplantation. Although these therapies have been reported to be useful, there are many issues in terms of the durability, complications, limited donors, adverse effect of continuous administration of immunosuppressive agents, and high costs involved. Recently, regenerative therapy based on genetic, cellular, or tissue engineering techniques has gained attention as a new therapy to overcome the challenges encountered in transplantation medicine...
January 2017: Kyobu Geka. the Japanese Journal of Thoracic Surgery
https://www.readbyqxmd.com/read/28170174/transplantation-of-donor-origin-mouse-embryonic-stem-cell-derived-thymic-epithelial-progenitors-prevents-the-development-of-chronic-graft-versus-host-disease-in-mice
#20
Rong Hu, Yalan Liu, Min Su, Yinhong Song, Debra Rood, Laijun Lai
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft-versus-host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T-cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD...
January 2017: Stem Cells Translational Medicine
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