Abstract:
:The novel immunosuppressive agents malononitrilamides (MNA) 279 and 715 are derivatives of A77 1726, the primary metabolite of leflunomide. The effects of these agents have been previously demonstrated in rat skin and cardiac allo- and xenotransplant models. The aim of this study was to evaluate the combination of MNA and tacrolimus in a high-responder rat cardiac allotransplant model. Graft survival was evaluated following 10 days of post-transplant oral therapy of MNA or tacrolimus alone and the drugs combined in PVG recipients of DA grafts. An iso-effect curve of single and combined drugs was constructed. Histological changes in grafts were evaluated at 10 days. MNA (20 mg/kg) or tacrolimus (2.4 mg/kg) alone prolonged graft survival with median survival of 14 and 13.5 days, respectively. Combined therapy of MNA (10 mg/kg) and tacrolimus 1.6 mg/kg likewise resulted in a median survival of 13.25 days and an iso-effect curve for these doses was constructed. Another iso-effect curve for median graft survival of 18-19 days, including MNA (10 mg/kg) + tacrolimus (3.2 mg/kg) in combination, MNA (30 mg/kg) alone and tacrolimus (4.8 mg/kg) alone, was constructed and both isoboles showed a straight line, demonstrating additive effects (zero interaction). In addition, histological analysis of grafts confirmed the benefit of the drug combination. No additional toxicity was noted with combined therapy. Optimal doses of MNA or tacrolimus had comparative effects on graft survival and histological changes, and a combination of the two drugs was beneficial with respect to both these parameters. The iso-effect curves verified additive effects of the drug combination.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Qi Z,Simanaitis M,Ekberg Hdoi
10.1016/s0966-3274(99)80036-7subject
Has Abstractpub_date
1999-09-01 00:00:00pages
169-75issue
3eissn
0966-3274issn
1878-5492pii
S0966-3274(99)80036-7journal_volume
7pub_type
杂志文章abstract:BACKGROUND:Donor specific hematopoietic cell transplantation has long been recognized for its potential in tolerance induction for subsequently transplanted organs. We have recently published that co-administration of Myeloid Progenitor (MP) and third party Hematopoietic Stem Cells (HSC) can induce MP-specific toleranc...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2014.04.001
更新日期:2014-08-01 00:00:00
abstract::Transplant rejection is a multifactorial process involving complex interactions between components of the innate and the acquired immune system. In view of the shortage of donor organs available for transplantation, xenotransplantation of pig organs into man has been considered as a potential solution. However, in com...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00042-4
更新日期:2002-05-01 00:00:00
abstract::Circulating host lymphocytes recognize, bind to, become activated by, and infiltrate engrafted allogeneic tissues. The mechanisms responsible for these early events which lead to acute immunological rejection have not been precisely defined. We have examined sequentially in vitro lymphocyte binding patterns in a kidne...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(95)80035-2
更新日期:1995-06-01 00:00:00
abstract::Pancreas grafts do not survive for lengthy periods, especially in a high-responder rat combination. Recent data indicated that a combined spleen/pancreas graft protects against acute graft rejection and induces donor-specific tolerance. In this study, we performed a combination spleen/pancreas transplantation using hi...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00049-1
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVES:To assess the timelines of serum free light chain (sFLC) concentrations and the kappa/lambda light chain (K/L) ratio in heart transplant (HTX) recipients. To analyze the performance of serum protein electrophoresis (SPE), serum immunofixation (sIFE) and sFLC measurements for gammopathy detection following a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2017.01.003
更新日期:2017-03-01 00:00:00
abstract:OBJECTIVE:Acute rejection is a major cause of morbidity and mortality after solid organ transplantation. Therefore, optimizing treatment strategies and improving curative effect is urgent and necessary. Reliable biomarkers for acute rejection and the underlying molecular mechanisms remain to be determined. METHODS:In ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101320
更新日期:2020-10-01 00:00:00
abstract::The means by which methotrexate (MTX) mediates immunosuppression at low doses remains to be elucidated. MTX has been shown to inhibit the adherence of neutrophils and fibroblasts to endothelial cells in vitro. The hypothesis that MTX treatment may affect cellular adherence by downregulating cell adhesion molecule expr...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(98)80026-9
更新日期:1998-06-01 00:00:00
abstract::Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal gra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.09.002
更新日期:2008-11-01 00:00:00
abstract::Cellular and antibody-mediated rejection processes and also interstitial fibrosis/tubular atrophy (IFTA) lead to allograft dysfunction and loss. The search for accurate, specific and non-invasive diagnostic tools is still ongoing and essential for successful treatment of renal transplanted patients. Molecular markers ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.09.003
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.04.004
更新日期:2005-10-01 00:00:00
abstract::Mycophenolate mofetil (MMF) a potent immunosuppressive agent, has recently been approved for clinical use (CellCept) in renal transplant patients in combination with cyclosporine (CsA). With the expanded use of tacrolimus (Prograf) as well in renal transplant patients, there is a lack of pharmacokinetic studies clarif...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/s0966-3274(97)80042-1
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:Donor passenger leukocytes (DPLs) that migrate after organ transplantation stimulate the recipient immune system and normally cause rejection and graft vs. host reaction. However, DPLs also contribute to the unresponsiveness to the donor organ. The quantity and quality of these migrating cells are considered...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2003.10.001
更新日期:2004-01-01 00:00:00
abstract::TIRC7 delivers essential signals during immune activation as antibodies targeting TIRC7 inhibit lymphocyte proliferation and Th1 cytokine expression in vitro and prolonged kidney and heart allograft survival in vivo. Immunohistochemical analysis of biopsy specimens from human renal allografts undergoing rejection desp...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.027
更新日期:2006-11-01 00:00:00
abstract::RNA interference (RNAi) has recently emerged as an efficient method to silence gene expression in mammalian cells by transfection of small interfering RNAs (siRNAs). The Janus kinase 3 (JAK3) is also pertinent to the development of a new immuno-suppressant. This study aimed to inhibit JAK3 expression using RNAi to det...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2009.02.004
更新日期:2009-05-01 00:00:00
abstract::Although the clinical significance of anti-HLA antibodies in heart and lung transplantation is less well studied than in renal transplantation, several studies have shown that heart and lung recipients transplanted in the presence of donor-specific antibodies are at increased risk for early acute rejection and have a ...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2004.01.005
更新日期:2004-06-01 00:00:00
abstract::4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, interacts with 4-1BBL expressed on APC and delivers a costimulatory signal for T cell activation and growth. In this study, we investigated the efficacy of an adenoviral vector encoding murine 4-1BB extracellular domain and human IgG1 Fc (Ad4-1BB...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.03.010
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drug...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2004.05.003
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (R+D-) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft. METHODS:We analyzed the duratio...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.04.003
更新日期:2018-08-01 00:00:00
abstract::MicroRNAs are small, noncoding RNAs that control expression of target genes through inhibiting protein translation or inducing degradation of mRNA transcripts of target genes. According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of mult...
journal_title:Transplant immunology
pub_type: 临床试验,杂志文章
doi:10.1016/j.trim.2017.06.002
更新日期:2017-08-01 00:00:00
abstract::In recent years, the utility of vascular complement factor 4d (C4d) deposition as diagnostic tool for antibody mediated rejection (AMR) after lung transplantation, has become a controversial issue. We aimed to pinpoint the problematic nature of C4d as biomarker with a simple experiment. We quantified C4d in broncho-al...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101352
更新日期:2021-02-01 00:00:00
abstract:BACKGROUND:After lung transplantation, the major complication limiting the long-term survival of allografts is obliterative bronchiolitis (OB), characterized by chronic rejection. Innate immune responses contribute to the development of OB. In this study, we used a murine heterotopic tracheal transplantation mouse mode...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.11.006
更新日期:2019-04-01 00:00:00
abstract::It is known that the expression level of the heat shock protein (HSP) is elevated in allograft tissues, but the specific role of the HSP in the acute rejection has not been elucidated. This study aims to determine how and when the HSP72 molecule works immunologically in the process of acute allograft rejection from a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2004.08.003
更新日期:2004-12-01 00:00:00
abstract::Induction and maintenance immunosuppression protocols with or without long-term steroid therapy in kidney transplant recipients are variable and are transplant center-specific. The aim of this prospective randomized pilot study was to compare 5-year outcomes in kidney recipients maintained on 4 different calcineurin i...
journal_title:Transplant immunology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.trim.2008.08.005
更新日期:2008-11-01 00:00:00
abstract::Naturally occurring antibodies to the galactose alpha1,3 galactose (alpha gal) epitope expressed on xenogeneic grafts are a major barrier to organ transplantation in humans. Porcine small intestinal submucosa (SIS) expresses the alpha gal epitope and is currently being used as a bioscaffold for tissue remodeling. To e...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00044-2
更新日期:2002-06-01 00:00:00
abstract::We have developed a highly sensitive method for the simultaneous crossmatching of T and B cells using three-colour flow cytometry. This method identifies T and B cell populations in a lymphocyte sample and analyses each for the presence of bound patient IgG alloantibodies. A fluorescein isothiocyanate conjugated rabbi...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(96)80018-9
更新日期:1996-09-01 00:00:00
abstract::Previously, we established a murine model, that involves the engraftment of fully allogeneic T cell depleted donor bone marrow cells in sublethally irradiated and single dose anti-CD3 treated recipient mice. These mice developed permanent stable multilineage mixed chimerism and donor-specific tolerance without graft-v...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/S0966-3274(02)00157-0
更新日期:2003-07-01 00:00:00
abstract::The rapid emergence of the COVID-19 pandemic is unprecedented and poses an unparalleled obstacle in the sixty-five year history of organ transplantation. Worldwide, the delivery of transplant care is severely challenged by matters concerning - but not limited to - organ procurement, risk of SARS-CoV-2 transmission, sc...
journal_title:Transplant immunology
pub_type: 社论
doi:10.1016/j.trim.2020.101304
更新日期:2020-08-01 00:00:00
abstract::A rapid and robust limiting dilution assay was developed to measure the frequency of donor-reactive, IL-2 (interleukin 2) producing, helper T lymphocytes in the peripheral T cell population of organ allograft recipients. The IL-2 bioassay was performed using two methodologies to assess the response of CTLL-2 indicator...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90006-x
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND:The complexity of surgical procedure in mouse heterotopic heart transplantation (HHT) has prevented its widespread use. The present study reported a modified technique - splint tubing technique (STT) based on cuff technique (CT). MATERIALS AND METHODS:C57BL/10 and BALB/c mice were performed in syngeneic and...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.03.005
更新日期:2011-07-01 00:00:00
abstract:BACKGROUND:We recently reported that autoreactive antibody (Ab) against nuclear histone H1 had been identified as an immunosuppressive factor in a rat tolerogenic orthotopic liver transplantation (OLT) model. The present study aimed to determine whether the up-regulation of antihistone H1 Ab by histone H1 vaccination l...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.01.003
更新日期:2007-04-01 00:00:00