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Transplant tolerance

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https://www.readbyqxmd.com/read/28641099/reduced-intensity-versus-myeloablative-allogeneic-transplantation
#1
REVIEW
Daniel J Weisdorf
Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The spectrum of conditioning intensity influences toxicities and non-relapse mortality. The spectrum of tumor sensitivity to the GVL response influences relapse. Balancing tolerable toxicities (influenced by patients' performance status and comorbidities) is also influenced by the graft. Intense immunosuppression (for engraftment and graft-versus-host disease prevention) may constrain the immunologic potency of the graft and limit the antineoplastic capacity of the transplant, thus requiring more intense or more effective conditioning regimens to limit the risks of relapse and permit satisfactory disease-free survival...
June 14, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28637347/mechanisms-underlying-the-long-term-survival-of-the-monocot-dracaena-marginata-under-drought-conditions
#2
Radek Jupa, Roman Plichta, Zuzana Paschová, Nadezhda Nadezhdina, Roman Gebauer
Efficient water management is essential for the survival of vascular plants under drought stress. While interrelations among drought stress, plant anatomy and physiological functions have been described in woody dicots, similar research is very limited for non-palm arborescent and shrubby monocots despite their generally high drought tolerance. In this study, potted transplants of Dracaena marginata Lam. in primary growth stage were exposed to several short- and long-term drought periods. Continuous measurements of sap flow and stem diameter, the evaluation of capacitance and leaf conductance, the quantification of non-structural carbohydrates (NSC), and organ-specific anatomical analyses were performed to reveal the mechanisms promoting plant resistance to limited soil moisture...
June 14, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28632754/permissive-hypercapnia-for-severe-acute-respiratory-distress-syndrome-in-immunocompromised-children-a-single-center-experience
#3
Hans Fuchs, Nicola Rossmann, Manuel B Schmid, Manfred Hoenig, Ulrich Thome, Benjamin Mayer, Daniel Klotz, Helmut D Hummler
BACKGROUND: Controlled hypoventilation while accepting hypercapnia has been advocated to reduce ventilator-induced lung injury. The aim of the study was to analyze outcomes of a cohort of immunocompromised children with acute respiratory distress syndrome (ARDS) ventilated with a strategy of stepwise increasing PCO2 targets up to 140 mm Hg. METHODS: Retrospective analysis of outcomes of a cohort of children with oncologic disease or after stem cell transplantation and severe respiratory failure in comparison with a historical control cohort...
2017: PloS One
https://www.readbyqxmd.com/read/28628776/3d-printed-lattices-as-an-activation-and-expansion-platform-for-t-cell-therapy
#4
Bahman Delalat, Frances Harding, Batjargal Gundsambuu, Elena M De-Juan-Pardo, Felix M Wunner, Marie-Luise Wille, Marek Jasieniak, Kristen A L Malatesta, Hans J Griesser, Antonio Simula, Dietmar W Hutmacher, Nicolas H Voelcker, Simon C Barry
One of the most significant hurdles to the affordable, accessible delivery of cell therapy is the cost and difficulty of expanding cells to clinically relevant numbers. Immunotherapy to prevent autoimmune disease, tolerate organ transplants or target cancer critically relies on the expansion of specialized T cell populations. We have designed 3D-printed cell culture lattices with highly organized micron-scale architectures, functionalized via plasma polymerization to bind monoclonal antibodies that trigger cell proliferation...
June 7, 2017: Biomaterials
https://www.readbyqxmd.com/read/28626459/the-immunogenicity-and-immune-tolerance-of-pluripotent-stem-cell-derivatives
#5
REVIEW
Xin Liu, Wenjuan Li, Xuemei Fu, Yang Xu
Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28622062/novel-zinc-finger-protein-gene-469-znf469-variants-in-advanced-keratoconus
#6
Elvin Yildiz, Handan Bardak, Murat Gunay, Yavuz Bardak, Serhat Imamoglu, Halil Ozbas, Ozkan Bagci
PURPOSE: Common polymorphic variants upstream of Zinc finger protein gene 469 (ZNF469) have been associated with central corneal thickness. Rare ZNF469 variants have been shown in keratoconus patients. The aim of the current study was to investigate the frequency of ZNF 469 gene variants in rapidly progressive advance keratoconus patients who underwent corneal transplant surgery by the age of 30, compared to their frequency in the normal Turkish population. METHODS: A search in a patient database was performed to identify patients with a rapidly progressive keratoconus requiring corneal transplant surgery by the age of 30 in at least one eye...
June 16, 2017: Current Eye Research
https://www.readbyqxmd.com/read/28621766/autologous-haematopoietic-stem-cell-transplantation-for-treatment-of-multiple-sclerosis
#7
REVIEW
Paolo A Muraro, Roland Martin, Giovanni Luigi Mancardi, Richard Nicholas, Maria Pia Sormani, Riccardo Saccardi
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ∼20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials...
June 16, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28620927/bendamustine-for-relapsed-blastic-plasmacytoid-dendritic-cell-leukaemia
#8
Sarah Bétrian, Sarah Guenounou, Isabelle Luquet, Cécile Demur, Anne Huynh, Loïc Ysebaert, Christian Recher, Françoise Huguet
Optimal treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN), a rare entity of dismal prognosis previously described as CD4+/CD56+ hematodermic malignancies, is not defined. We report five cases of relapsed BPDCN treated with bendamustine hydrochloride, a well-tolerated bifunctional drug acting as an alkylating and antimetabolite agent. All patients were above the age of 50 years and in advanced disease (early first relapse in two, subsequent relapse in three; multi-organ involvement in four; previous intensive chemotherapy in five; and stem cell transplantation in four)...
June 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28620237/lea29y-expression-in-transgenic-neonatal-porcine-islet-like-cluster-promotes-long-lasting-xenograft-survival-in-humanized-mice-without-immunosuppressive-therapy
#9
L Wolf-van Buerck, M Schuster, F S Oduncu, A Baehr, T Mayr, S Guethoff, J Abicht, B Reichart, N Klymiuk, E Wolf, J Seissler
Genetically engineered pigs are a promising source for islet cell transplantation in type 1 diabetes, but the strong human anti-pig immune response prevents its successful clinical application. Here we studied the efficacy of neonatal porcine islet-like cell clusters (NPICCs) overexpressing LEA29Y, a high-affinity variant of the T cell co-stimulation inhibitor CTLA-4Ig, to engraft and restore normoglycemia after transplantation into streptozotocin-diabetic NOD-SCID IL2rγ(-/-) (NSG) mice stably reconstituted with a human immune system...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619624/fetal-stem-cell-and-gene-therapy
#10
REVIEW
Russell Witt, Tippi C MacKenzie, William H Peranteau
Advances in our understanding of stem cells, gene editing, prenatal imaging and fetal interventions have opened up new opportunities for the treatment of congenital diseases either through in-utero stem cell transplantation or in-utero gene therapy. Improvements in ultrasound-guided access to the fetal vasculature have also enhanced the safety and efficacy of cell delivery. The fetal environment offers accessible stem cell niches, localized cell populations with large proliferative potential, and an immune system that is able to acquire donor-specific tolerance...
June 12, 2017: Seminars in Fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28611776/editorial-transplant-rejection-and-tolerance-advancing-the-field-through-integration-of-computational-and-experimental-investigation
#11
EDITORIAL
Giorgio Raimondi, Kathryn J Wood, Alan S Perelson, Julia C Arciero
No abstract text is available yet for this article.
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611473/apc-targeted-proinsulin-expression-inactivates-insulin-specific-memory-cd8-t-cells-in-nod-mice
#12
Peta Ls Reeves, Rajeev Rudraraju, Xiao Liu, F Susan Wong, Emma E Hamilton-Williams, Raymond J Steptoe
Type 1 diabetes (T1D) results from T-cell mediated autoimmune destruction of pancreatic β cells. Effector T-cell responses emerge early in disease development and expand as disease progresses. Following β cell destruction, a long-lived T-cell memory is generated that represents a barrier to islet transplantation and other cellular insulin-replacement therapies. Development of effective immunotherapies that control or ablate β cell destructive effector and memory T cell responses has the potential to prevent disease progression and recurrence...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610444/midostaurin-for-the-treatment-of-acute-myeloid-leukemia
#13
Mrinal M Patnaik
Midostaurin is a multikinase tyrosine kinase inhibitor acting against targets known to be expressed in hematologic malignancies, especially acute myeloid leukemia. Midostaurin combined with chemotherapy followed by single-agent maintenance therapy elicited statistically significant and clinically meaningful improvement in overall survival versus placebo in patients with newly diagnosed FLT3-mutant acute myeloid leukemia. Although gastrointestinal events were more common with midostaurin, overall the drug was relatively well tolerated...
June 14, 2017: Future Oncology
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#14
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28606879/can-immunosuppression-be-stopped-after-liver-transplantation
#15
REVIEW
Pierre-Alain Clavien, Xavier Muller, Michelle L de Oliveira, Philipp Dutkowski, Alberto Sanchez-Fueyo
Liver transplantation has improved dramatically over the past three decades, mainly as a result of advances in surgical techniques and management of post-transplant complications. The focus has now turned towards rescuing additional organs in the face of scarce organ supply, or prevention of long-term toxicity associated with immunosuppression. The liver appears to be privileged in terms of immune tolerance, with a low incidence of antibody-mediated rejection, which is in sharp contrast to other solid organ transplants, such as kidney, lung, and heart transplants...
July 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28604446/evolving-approaches-in-the-identification-of-allograft-reactive-t-and-b-cells-in-mice-and-humans
#16
James S Young, Christine McIntosh, Maria-Luisa Alegre, Anita S Chong
Whether a transplanted allograft is stably accepted, rejected or achieves immunological tolerance is dependent on the frequency and function of alloreactive lymphocytes, making the identification and analysis of alloreactive T and B cells in transplant recipients critical for understanding mechanisms, and the prediction of allograft outcome. In animal models, tracking the fate of graft-reactive T and B cells allows investigators to uncover their biology and develop new therapeutic strategies to protect the graft...
June 8, 2017: Transplantation
https://www.readbyqxmd.com/read/28603052/efficacy-and-safety-of-mycophenolate-mofetil-and-tacrolimus-as-second-line-therapy-for-patients-with-autoimmune-hepatitis
#17
Cumali Efe, Hannes Hagström, Henriette Ytting, Rahima A Bhanji, Niklas F Müller, Qixia Wang, Tugrul Purnak, Luigi Muratori, Mårten Werner, Hanns-Ulrich Marschall, Paolo Muratori, Fulya Gunşar, Daniel Klintman, Albert Parés, Alexandra Heurgué-Berlot, Thomas D Schiano, Mustafa Cengiz, Michele May-Sien Tana, Xiong Ma, Aldo J Montano-Loza, Thomas Berg, Sumita Verma, Fin Stolze Larsen, Ersan Ozaslan, Michael A Heneghan, Eric M Yoshida, Staffan Wahlin
BACKGROUND: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. PATIENTS AND METHODS: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6-190 months)...
June 8, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28597329/safety-and-efficacy-of-mogamulizumab-in-patients-with-adult-t-cell-leukemia-lymphoma-in-japan-interim-results-of-postmarketing-all-case-surveillance
#18
Kenji Ishitsuka, Satoshi Yurimoto, Kouichi Kawamura, Yukie Tsuji, Manabu Iwabuchi, Takeshi Takahashi, Kensei Tobinai
We present the interim results of a postmarketing all-case surveillance study in patients with C-C chemokine receptor 4 (CCR4)-positive, relapsed or refractory adult T-cell leukemia-lymphoma (ATL) treated with the anti-CCR4 monoclonal antibody mogamulizumab since its 2012 launch in Japan. The safety and efficacy analysis populations comprised 484 and 442 patients, respectively. The ATL subtype was acute in 58.9% and lymphoma in 34.2% of patients. All patients were scheduled to receive intravenous infusions of mogamulizumab (1...
June 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28595696/left-main-coronary-artery-compression-in-patients-with-pulmonary-arterial-hypertension-and%C3%A2-angina
#19
Nazzareno Galiè, Francesco Saia, Massimiliano Palazzini, Alessandra Manes, Vincenzo Russo, Maria Letizia Bacchi Reggiani, Gianni Dall'Ara, Enrico Monti, Fabio Dardi, Alessandra Albini, Andrea Rinaldi, Enrico Gotti, Nevio Taglieri, Cinzia Marrozzini, Luigi Lovato, Maurizio Zompatori, Antonio Marzocchi
BACKGROUND: Left main coronary artery (LMCA) compression is increasingly recognized as a cause of angina in pulmonary arterial hypertension (PAH). OBJECTIVES: This study aimed to evaluate the prevalence of LMCA extrinsic compression from a dilated pulmonary artery (PA) in patients with PAH and angina or angina-like symptoms, determine the usefulness of screening with computed tomography coronary angiography (CTCA), and assess the safety and efficacy of percutaneous coronary interventions (PCIs)...
June 13, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28592040/-surgical-treatment-of-severe-refractory-hemorrhagic-cystitis-following-allogeneic-hematopoietic-stem-cell-transplantation-a-report-of-17-patients
#20
F F Tang, X H Zhang, H Chen, Y Y Chen, W Han, J Z Wang, F R Wang, Y Chen, X J Huang, L P Xu
Objective: To investigate the clinical effect and safety of surgical treatment for severe, refractory hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: Patients with severe HC, who were admitted to Peking University Institute of Hematology from January 2010 to December 2015, were enrolled in this study.All patients were refractory to medical managements and received bladder surgery including mucous electrocoagulation and/or selective transcatheter arterial embolization...
June 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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