Abstract:
BACKGROUND:The genetic modification of pigs is a powerful strategy that may ultimately enable successful xenotransplantation of porcine organs into humans. METHODS:Transgenic pigs were produced by microinjection of gene constructs for human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2-fucosyltransferase (H-transferase, HT), which reduces expression of the major xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and CD55/CD59/HT transgenic pigs were transplanted into nephrectomised, nonimmunosuppressed adult baboons. RESULTS:In several lines of transgenic pigs, CD55 and CD59 were expressed strongly in all tissues examined, whereas HT expression was relatively weak and did not significantly reduce alphaGal. Control nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30 hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5 days. In the latter grafts, infiltration by macrophages, T cells, and B cells was observed at days 3 and 5 posttransplantation. The recipients developed thrombocytopenia and abnormalities in coagulation, manifested in increased clotting times and an elevation in the plasma level of the fibrin degradation product D-dimer, within 2 days of transplantation. Treatment with low molecular weight heparin prevented profound thrombocytopenia but not the other aspects of coagulopathy. CONCLUSIONS:Strong expression of CD55 and CD59 completely protected porcine kidneys from hyperacute rejection and allowed a detailed analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy appears to be a common feature of pig-to-baboon renal transplantation and represents yet another major barrier to its clinical application.
journal_name
Transplantationjournal_title
Transplantationauthors
Cowan PJ,Aminian A,Barlow H,Brown AA,Chen CG,Fisicaro N,Francis DM,Goodman DJ,Han W,Kurek M,Nottle MB,Pearse MJ,Salvaris E,Shinkel TA,Stainsby GV,Stewart AB,d'Apice AJdoi
10.1097/00007890-200006270-00008subject
Has Abstractpub_date
2000-06-27 00:00:00pages
2504-15issue
12eissn
0041-1337issn
1534-6080journal_volume
69pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract:BACKGROUND:Generation of non-human primate regulatory T cells (Treg) with alloantigen (alloAg) specificity would allow their testing in preclinical transplant models. Low recovery of Treg from peripheral blood limits their potential utility. In small animals and humans, conventional myeloid dendritic cells (DC) have be...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181ba6b1f
更新日期:2009-11-15 00:00:00
abstract::The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199110000-00007
更新日期:1991-10-01 00:00:00
abstract::Donor-specific blood transfusion (DSBT) in animals and humans can either promote subsequent renal graft survival or lead to sensitization and graft rejection. Using a rat renal allograft model, we have examined whether the effects of DSBT on renal allograft outcome and IgG alloantibody responses are linked to the host...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199309000-00033
更新日期:1993-09-01 00:00:00
abstract::Mouse thyroid tissue was dissociated with collagenase, fixed in periodate-lysine-paraformaldehyde (PLP), and further dissociated with EDTA and trypsin to yield cell suspensions containing mainly follicle epithelial cells and vascular endothelial cells. H-2 complex antigens were detected on the vascular endothelial cel...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198008000-00013
更新日期:1980-08-01 00:00:00
abstract:BACKGROUND:Chronic allograft dysfunction (CAD) is a complex phenomenon caused by underlying kidney disease and superimposed environmental and genetic factors. We investigated the association of polymorphisms in the genes for angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II receptor type 1 (ATR...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000134972.81306.b1
更新日期:2004-09-27 00:00:00
abstract::To determine if cold preservation time continues to affect renal transplant outcome, prospectively collected data from 17,937 cadaveric renal transplants performed between 1982 and 1991 were analyzed. Cold preservation intervals of 1-16, 16-32, 32-48, and greater than 48 hr were studied by multi- and univariate method...
journal_title:Transplantation
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-01-27 00:00:00
abstract::We had previously shown in a canine model that the administration of anti-MHC class II monoclonal antibody (MAB) immediately after autologous marrow transplantation prevented hemopoietic reconstitution. Since MHC class II expression in mice differs from that in dogs we were interested in determining the effect of MHC ...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1994-12-27 00:00:00
abstract::Infectious complications in patients with recurrent hepatitis C virus (HCV) hepatitis after liver transplantation were prospectively assessed and compared with those of all other liver transplant recipients without HCV hepatitis operated on during the same period. Major infections occurred in 64% (14/22) of the patien...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199602150-00014
更新日期:1996-02-15 00:00:00
abstract::Patients receiving allogeneic marrow transplantation for hematologic malignancies commonly are conditioned with total body irradiation (TBI) and given methotrexate (MTX) in an attempt to prevent graft-versus-host disease. To study the effects of TBI with or without MTX on bronchoalveolar cells and proteins, we perform...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198404000-00003
更新日期:1984-04-01 00:00:00
abstract::Antihuman lymphocyte rabbit (or horse) gamma globulins used in recipients of organ transplantation are prepared against thymocytes or immortalized cell lines, the only two sources so far allowing enough antigen preparation. These cells lack, however, the surface determinants characteristic of alloreactive blasts invol...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198908000-00014
更新日期:1989-08-01 00:00:00
abstract::Living donor renal allograft survival is superior to that achieved from deceased donors, although graft outcome is suboptimal in some of these patients. In an effort to identify the subset of patients at high risk for poor outcomes we studied donor risk factors in 248 living kidney donor-recipient pairs. Unadjusted do...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000256284.78721.ba
更新日期:2007-03-15 00:00:00
abstract:BACKGROUND:Donor T cells are primarily responsible for graft-versus-host disease (GVHD). Three effector pathways have been described for T-cell cytotoxicity: granzyme B/perforin, Fas/Fas ligand (FasL), and secreted molecules such as tumor necrosis factor (TNF)-alpha. Therefore, this study evaluates the gene expression ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.TP.0000100465.83529.42
更新日期:2004-01-27 00:00:00
abstract::To investigate whether graft-versus-host reactivity (GVHR) and the graft-versus-leukemia (GVL) effect can be differentiated, C3H-->AKR mixed bone marrow (BM) chimeras were prepared using two different conditioning regimens. Total body irradiation (TBI) chimeras were induced by infusing 5 x 1O(6) T cell depleted syngen...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199603150-00025
更新日期:1996-03-15 00:00:00
abstract:BACKGROUND:Hyperacute rejection (HAR) of pig-to-primate discordant xenografts is caused by the deposition of preexisting natural antibodies that recognize Galalpha1-3Gal (alphaGal)-terminating oligosaccharides on glycoproteins and glycolipids, followed by complement-mediated lysis of the graft's endothelium. In vitro, ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199802150-00009
更新日期:1998-02-15 00:00:00
abstract:BACKGROUND:A combined liver and kidney transplantation (CLKT) is advocated for selected individuals with chronic kidney disease undergoing liver transplantation (LT). The aim was to develop a risk score to identify the patients whose estimated glomerular filtration rate (eGFR) would decline during the year post-LT to a...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181d9e195
更新日期:2010-06-15 00:00:00
abstract::Loss of bile ducts is a characteristic feature of chronic rejection in the liver allograft (also known as irreversible rejection and vanishing bile-duct syndrome). Typically, this occurs as a progressive lesion resulting in irreversible damage and graft failure requiring retransplantation. In this study, we describe 6...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199105000-00014
更新日期:1991-05-01 00:00:00
abstract::For maximum use of left liver plus caudate lobe grafts, the short hepatic vein draining the caudate lobe should be reconstructed. We devised a new venoplasty technique. On the graft side, a wide venous orifice with a long cuff was formed by gathering the left, middle, and short hepatic veins using a conduit vein graft...
journal_title:Transplantation
pub_type: 临床试验,杂志文章
doi:10.1097/01.tp.0000244729.39485.7c
更新日期:2007-01-27 00:00:00
abstract::LEW rats with long-surviving (> 100 days) (DA x LEW)F1 kidney allografts were generated by treating the recipients with cyclosporine for 14 days after grafting. All rats were monitored after transplantation for the development of antibodies to intact donor class I MHC molecules. Cyclosporine completely suppressed the ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199605270-00007
更新日期:1996-05-27 00:00:00
abstract::Data from 60 consecutive ABO-incompatible kidney transplantations performed in Stockholm, Sweden; Freiburg, Germany; and Uppsala, Sweden, revealed significant variation in preoperative A/B antibody levels, with median titers of 1:32, 1:128, and 1:8, respectively. We wanted to investigate whether these differences were...
journal_title:Transplantation
pub_type: 杂志文章,多中心研究
doi:10.1097/01.tp.0000296019.85986.af
更新日期:2007-12-27 00:00:00
abstract:BACKGROUND:We previously reported that posttransplant lymphoproliferative disorders (PTLD) occurred more frequently in non-African American (AF) kidney transplant recipients. An in-depth analysis of racial differences in the development of PTLD has not been reported. METHODS:We assessed Medicare claims for PTLD in a r...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3182200e8a
更新日期:2011-07-27 00:00:00
abstract::Recent reports document the efficacy of transjugular intrahepatic portocaval shunts (TIPS) for the prevention of portal hypertensive bleeding and have advocated its use as a bridge to liver transplantation. There are no reports, however, analyzing liver transplant results for patients with indwelling TIPS. We reviewed...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1994-08-15 00:00:00
abstract:BACKGROUND:Successful islet transplantation can result in insulin independence in many patients with type 1 diabetes mellitus, but it often requires more than one islet infusion. The ability to achieve insulin independence with a single donor is an important goal in clinical islet transplantation due to the limited org...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181c478fd
更新日期:2010-02-27 00:00:00
abstract:BACKGROUND:Prediabetic glucose homeostasis alterations are important cardiovascular risk factors but their role in renal transplant recipients (RTR) has not been established. METHODS:In 172 RTRs without pretransplant or de novo diabetes, we measured carotid intima media thickness (c-IMT) and performed an oral glucose ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000284462.70064.ae
更新日期:2007-10-15 00:00:00
abstract:BACKGROUND:In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear. METHODS:Using the...
journal_title:Transplantation
pub_type: 杂志文章,多中心研究
doi:10.1097/TP.0000000000000413
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial. METHODS:We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000003443
更新日期:2020-09-02 00:00:00
abstract:BACKGROUND:The spleen is considered to be an important secondary lymphoid organ where acute graft-versus-host disease (GVHD) is initiated by donor T cells that recognize host alloantigens after allogeneic bone-marrow transplantation (BMT). The influence of splenectomy on the development of GVHD prior to BMT has yet to ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200205270-00027
更新日期:2002-05-27 00:00:00
abstract:BACKGROUND:Data regarding the onset of puberty in children receiving mammalian target of rapamycin (mTOR) inhibitors are limited. METHODS:Kidney transplant patients aged <14 years were analyzed retrospectively to a maximum age of 18 years, with a minimal observation period of 1 year. Immunosuppression comprised (1) st...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000001037
更新日期:2016-11-01 00:00:00
abstract:BACKGROUND:Sotrastaurin (STN), a novel oral protein kinase C inhibitor that inhibits early T-cell activation, was assessed in non-human primate recipients of life-supporting kidney allografts. METHODS:Cynomolgus monkey recipients of life-supporting kidney allografts were treated orally with STN alone or in combination...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31823cf92f
更新日期:2012-01-27 00:00:00
abstract::The ability of the popliteal lymph node assay (PLNA) To detect host-versus-graft activity in response to H-Y antigens was investigated in the rat by using presensitized recipients. It was shown that significant popliteal lymph node (PLN) enlargement in response to H-Y-incompatible lymphocytes from syngeneic donors cou...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198103000-00013
更新日期:1981-03-01 00:00:00
abstract:BACKGROUND:Islet transplantation studies with diabetic rodents frequently use treatment with diabetogens such as alloxan or streptozotocin to render hosts hyperglycemic. These chemicals produce unwanted toxic side effects, which complicate interpretations of damage produced by hyperglycemia versus direct toxin-induced ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200204270-00024
更新日期:2002-04-27 00:00:00