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https://www.readbyqxmd.com/read/27914107/non-paraneoplastic-autoimmune-subepidermal-bullous-disease-associated-with-fatal-bronchiolitis-obliterans
#1
Mari Orime, Katsuhiro Tomiyama, Hideki Hashidate, Satoru Yoshida, Satoshi Hokari, Akiko Tsuda, Hisashi Yokoyama, Jun-Ichi Narita, Youhei Uchida, Takuro Kanekura, Riichiro Abe, Norito Ishii, Takashi Hashimoto, Kazuhiro Kawai
Bronchiolitis obliterans is a small-airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti-laminin-332-type mucous membrane pemphigoid in a patient with chronic graft-versus-host disease. We report a case of non-paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation...
December 3, 2016: Journal of Dermatology
https://www.readbyqxmd.com/read/27914091/toward-clinical-use-of-the-igg-specific-enzymes-ides-and-endos-against-antibody-mediated-diseases
#2
Mattias Collin, Lars Björck
The endoglycosidase EndoS and the protease IdeS from the human pathogen Streptococcus pyogenes are immunomodulating enzymes hydrolyzing human IgG. IdeS cleaves IgG in the lower hinge region, while EndoS hydrolyzes the conserved N-linked glycan in the Fc region. Both enzymes are remarkably specific for human IgG that after hydrolysis loses most of its effector functions, such as binding to leukocytes and complement activation, all contributing to bacterial evasion of adaptive immunity. However, taken out of their infectious context, we and others have shown that IdeS and EndoS can alleviate autoimmune disease in a number of animal models of antibody-mediated disorders...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27914026/limbal-stem-cell-and-oral-mucosal-epithelial-transplantation-from-ex-vivo-cultivation-in-lscd-induced-rabbits-histology-and-immunologic-study-of-the-transplant-epithelial-sheet
#3
Napaporn Tananuvat, Kanokkan Bumroongkit, Chainarong Tocharusa, Umnat Mevatee, Aphisek Kongkaew, Somsanguan Ausayakhun
PURPOSE: To evaluate the results of cultivated limbal epithelial and oral mucosal epithelial transplantation (CLET and COMET) in limbal stem cell deficiency (LSCD)-induced rabbit model. MATERIALS AND METHODS: Six New Zealand white rabbits were divided into two groups of three rabbits each. Limbal tissue was harvested from the first group, and oral mucosal biopsy was obtained from the second group. The tissues were cultured using an explant technique with amniotic membrane as a substrate and co-culture with the 3T3 fibroblast and air-lifting method...
December 2, 2016: International Ophthalmology
https://www.readbyqxmd.com/read/27913900/bone-mineral-density-of-extremities-is-associated-with-coronary-calcification-and-biopsy-verified-vascular-calcification-in-living-donor-renal-transplant-recipients
#4
Zhimin Chen, Jia Sun, Mathias Haarhaus, Peter Barany, Lars Wennberg, Jonaz Ripsweden, Torkel B Brismar, Bengt Lindholm, Annika Wernerson, Magnus Söderberg, Peter Stenvinkel, Abdul Rashid Qureshi
Chronic kidney disease (CKD) mineral and bone disorders (CKD-MBD) may lead to low bone mineral density (BMD) and vascular calcification (VC), but links to the latter are unclear. Here we investigated associations between BMD, coronary artery calcium (CAC) scores, and histological signs of VC in end-stage renal disease (ESRD) patients undergoing living-donor kidney transplantation (LD-Rtx). In 66 ESRD patients (median age 45 years, 68% males), BMD (by dual-energy X-ray absorptiometry, DXA), CAC score (by computed tomography, CT; n = 54), and degree of VC score (graded by histological examination of epigastric artery specimens collected at LD-Rtx; n = 55) were assessed at the time of LD-Rtx...
December 2, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/27913896/mesenchymal-stem-cells-with-enos-over-expression-enhance-cardiac-repair-in-rats-with-myocardial-infarction
#5
Leilei Chen, Yuan Zhang, Liangliang Tao, Zhijian Yang, Liansheng Wang
PURPOSE: Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. METHODS: We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. RESULTS: Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo...
December 3, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27913812/association-between-cytokines-and-their-receptor-antagonist-gene-polymorphisms-and-clinical-risk-factors-and-acute-rejection-following-renal-transplantation
#6
SIqing Ding, Jianfei Xie, Qiquan Wan
BACKGROUND Acute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation...
December 3, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27913799/involvement-of-recipient-transplant-coordinators-in-transplant-outpatient-clinics-in-japan-current-status-and-transplant-physician-s-thoughts-on-follow-up-clinics
#7
Kuniko Hagiwara, Natsuko Seto, Yasuko Shimizu, Shiro Takahara
CONTEXT: Transplant recipients require long-term immunosuppressive therapy, so continued medical follow-up is necessary for long-term survival. OBJECTIVE: To investigate the current role of recipient transplant coordinators (RTCs) in the outpatient care of organ transplant recipients in Japan. METHODS: We sent a questionnaire survey to doctors in transplant facilities affiliated with the Japan Society for Transplantation probing attitudes on the role of RTCs in outpatient clinics...
December 2, 2016: Progress in Transplantation
https://www.readbyqxmd.com/read/27913685/novel-biomarkers-in-kidney-disease-roles-for-cilia-wnt-signalling-and-atmin-in-polycystic-kidney-disease
#8
REVIEW
Paraskevi Goggolidou, Patricia D Wilson
Biomarkers, the measurable indicators of biological conditions, are fast becoming a popular approach in providing information to track disease processes that could lead to novel therapeutic interventions for chronic conditions. Inherited, chronic kidney disease affects millions of people worldwide and although pharmacological treatments exist for some conditions, there are still patients whose only option is kidney dialysis and kidney transplantation. In the past 10 years, certain chronic kidney diseases have been reclassified as ciliopathies...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913630/adaptive-nkg2c-nk-cell-response-and-the-risk-of-cytomegalovirus-infection-in-kidney-transplant-recipients
#9
Dolores Redondo-Pachón, Marta Crespo, Jose Yélamos, Aura Muntasell, María José Pérez-Sáez, Silvia Pérez-Fernández, Joan Vila, Carlos Vilches, Julio Pascual, Miguel López-Botet
CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C(+) NK cells. The distribution of NKG2C(+) NK cells and NKG2C genotypes (NKG2C(+/+), NKG2C(+/del), NKG2C(del/del)) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts...
December 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#10
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
December 2, 2016: Genes & Development
https://www.readbyqxmd.com/read/27913534/myelodysplastic-and-myeloproliferative-disorders-of-childhood
#11
Henrik Hasle
Myelodysplastic syndrome (MDS) and myeloproliferative disorders are rare in children; they are divided into low-grade MDS (refractory cytopenia of childhood [RCC]), advanced MDS (refractory anemia with excess blasts in transformation), and juvenile myelomonocytic leukemia (JMML), each with different characteristics and management strategies. Underlying genetic predisposition is recognized in an increasing number of patients. Germ line GATA2 mutation is found in 70% of adolescents with MDS and monosomy 7. It is challenging to distinguish RCC from aplastic anemia, inherited bone marrow failure, and reactive conditions...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913531/treatment-of-older-patients-with-acute-lymphoblastic-leukemia
#12
Nicola Gökbuget
The treatment of older patients with acute lymphoblastic leukemia (ALL) is an unmet medical need. With increasing age, ALL patients have a significantly lower clinical remission rate, higher early mortality, higher relapse rate, and poorer survival compared with younger patients. This is only partly explained by a higher incidence of poor prognostic factors in the older age group. Most importantly, intensive chemotherapy with or without stem cell transplantation (SCT) is less well tolerated in older patients...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913527/myelofibrosis-to-transplant-or-not-to-transplant
#13
Rebecca Devlin, Vikas Gupta
Hematopoietic cell transplantation (HCT) is the only curative therapeutic modality for myelofibrosis (MF) at present. The optimal timing of HCT is not known in the presence of wider availability of less risky nontransplant therapies such as JAK 1/2 inhibitors. Careful review of patient, disease, and transplant-related factors is required in the appropriate selection of HCT vs the best available nontransplant therapies. We highlight some of the relevant issues and positioning of HCT in light of evolving data on JAK 1/2 inhibitors...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913524/cellular-and-vaccine-immunotherapy-for-multiple-myeloma
#14
Alfred L Garfall, Edward A Stadtmauer
Allogeneic hematopoietic cell transplantation and donor lymphocyte infusion for multiple myeloma (MM) can induce graft-versus-myeloma immunity and long-term survivorship, but limited efficacy and associated toxicities have prevented its widespread use. Cellular immunotherapies and vaccines seek to induce more specific, reliable, and potent antimyeloma immune responses with less treatment-related risk than is possible with allogeneic transplantation. Advances in molecular biology, and basic and applied immunology, have led to promising approaches such as genetically engineered T cells with chimeric antigen receptors and T-cell receptors targeting myeloma-specific epitopes, vaccine primed ex vivo expanded autologous T cells, expanded marrow-infiltrating lymphocytes, and plasma cell/dendritic cell fusion vaccines...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913522/role-of-stem-cell-transplant-and-maintenance-therapy-in-plasma-cell-disorders
#15
Philip L McCarthy, Sarah A Holstein
Autologous stem cell transplant (ASCT) has been an important component of therapy for myeloma patients eligible for high-dose chemotherapy. Recent studies comparing early transplant to low-dose chemotherapy support the continued use of ASCT as consolidation following induction therapy, even in the era of immunomodulatory drugs, proteasome inhibitors, and other novel agents. Despite the marked improvements in outcomes with this approach, most patients will eventually experience disease progression. Thus, inclusion of post-ASCT consolidation/maintenance strategies is used to improve long-term disease control...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913521/sequencing-of-nontransplant-treatments-in-multiple-myeloma-patients-with-active-disease
#16
Andrew J Yee, Noopur S Raje
The approval of several different classes of drugs in recent years has resulted in a dramatic expansion of treatment options for multiple myeloma patients, improving both survival and quality of life. Lenalidomide and bortezomib are now core components of treatment both at time of diagnosis and at relapse. Next-generation immunomodulatory drugs, like pomalidomide, and newer proteasome inhibitors like carfilzomib and ixazomib are available for use at relapse. Drugs with novel mechanisms of action such as the histone deacetylase inhibitor panobinostat and the monoclonal antibodies targeting SLAMF7 (elotuzumab) and CD38 (daratumumab) are significant steps forward...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913520/myeloma-management-of-the-newly-diagnosed-high-risk-patient
#17
Angela Dispenzieri
Although there have been many definitions for high-risk (HR) myeloma, most recent consensus for classifying risk in patients with newly diagnosed multiple myeloma (NMM) comes from the International Myeloma Working Group. This recently published revised International Staging System includes del(17p) or t(4;14) by fluorescence in situ hybridization, β-2 microglobulin, albumin, and lactate dehydrogenase. These elements should be captured in all NMM patients. The optimal treatments for HR myeloma have not been fully worked out; therefore, these patients should be considered for clinical trials...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913519/transplantation-for-myelodysplastic-syndromes-who-when-and-which-conditioning-regimens
#18
Wael Saber, Mary M Horowitz
Allogeneic hematopoietic stem cell transplantation (HCT) is the only curative therapy for myelodysplastic syndrome (MDS). Broad application is hindered by high risks of transplant-related morbidity and mortality, especially in the older age range represented by the MDS population. However, recent advances in strategies to minimize regimen-related toxicity make HCT a viable option for many more patients. Appropriate selection of patients involves consideration of patient factors, including use of geriatric assessment tools and comorbidity scales, that predict risks of regimen-related toxicity as well as disease factors, including genetic markers, which predict survival with both non-HCT and HCT therapy...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913518/treatment-options-for-patients-with-myelodysplastic-syndromes-after-hypomethylating-agent-failure
#19
Hetty E Carraway
The treatment of patients with myelodysplastic syndromes (MDSs) has hinged primarily on supportive care (ie, blood transfusions, colony stimulating agents, iron chelation, etc.) and the US Food and Drug Administration-approved agents, including 5-azacytidine, deoxyazacytidine, and lenalidomide. For patients no longer benefitting from these agents, there is a paucity of effective therapies. The challenges at this time include our limited understanding of the mechanisms of resistance to these therapies and the variables employed to select next best therapies for patients based on: (1) their performance status and medical comorbidities; (2) the molecular feature(s) of their MDS; (3) the prior treatments they have received; and (4) the long-term goal(s)/possibilities for their future treatment (ie, transplant vs no transplant)...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27913517/treatment-of-low-risk-myelodysplastic-syndromes
#20
Valeria Santini
The majority of myelodysplastic syndrome (MDS) patients belong to the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R) lower-risk categories. Their precise diagnostics and prognostic stratification is often a challenge, but may ensure the optimization of therapy. The availability of diverse treatment options has significantly improved the quality of life and survival of this group of patients. Anemia is the most relevant cytopenia in terms of frequency and symptoms in lower-risk MDS, and may be treated successfully with erythropoietic stimulating agents, provided a careful selection is performed on the basis of IPSS-R, endogenous erythropoietin levels, and transfusion independence...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
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