Abstract:
BACKGROUND:Primary hyperoxaluria type-1 (PH1) is an autosomal recessive disease characterized by excessive oxalate production by hepatocytes caused by the deficiency of peroxisomal alanine-glyoxylate aminotransferase (AGT) activity. Persistent hyperoxaluria causes nephrocalcinosis and urolithiasis, leading to renal failure, followed by tissue oxalosis with life-threatening complications. Combined liver-kidney transplantation is the only definitive treatment of PH1. Hepatocyte transplantation, which is much less invasive, could have offered an attractive alternative. However, because the AGT-deficient hepatocytes overproduce oxalate, a large fraction of the mutant host hepatocytes must be replaced by AGT-competent cells, which is beyond the capacity of current hepatocyte transplantation procedures. Here, we have evaluated a preparative irradiation-based method of liver repopulation in an Agxt-deleted mouse model of PH1 (Agxt-/-). MATERIALS AND METHODS:Hepatocytes (10(6) viable cells) isolated from congeneic mice ([ROSA]26 C57BL/6J) expressing Escherichia coli beta-galactosidase were transplanted into Agxt-/- mice by intrasplenic injection. The preparative regimen consisted of X-irradiation of the host liver and mitotic stimulation of the hepatocytes by adenovector-based expression of hepatocyte growth factor. RESULTS:The procedure resulted in progressive replacement of the mutant host hepatocytes with the AGT-competent hepatocytes, leading to correction of urinary oxalate excretion. Oral ethylene glycol challenge (0.7% for 1 week) resulted in nephrocalcinosis and microlithiasis in untreated Agxt-/- mice, but not in the mice after hepatic repopulation. CONCLUSION:The results indicate that hepatocyte transplantation after appropriate preparative regimens may permit sufficient repopulation of the liver to ameliorate hyperoxaluria, and therefore should be evaluated further as a potential treatment of PH1.
journal_name
Transplantationjournal_title
Transplantationauthors
Jiang J,Salido EC,Guha C,Wang X,Moitra R,Liu L,Roy-Chowdhury J,Roy-Chowdhury Ndoi
10.1097/TP.0b013e31816de49esubject
Has Abstractpub_date
2008-05-15 00:00:00pages
1253-60issue
9eissn
0041-1337issn
1534-6080pii
00007890-200805150-00007journal_volume
85pub_type
杂志文章相关文献
TRANSPLANTATION文献大全abstract::Weight gain following renal transplantation occurs frequently but has not been investigated quantitatively. A retrospective chart review of 115 adult renal transplant recipients was used to describe patterns of weight gain during the first 5 years after transplantation. Only 23 subjects (21%) were overweight before th...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199310000-00008
更新日期:1993-10-01 00:00:00
abstract::Blood transfusions are common in patients with end-stage liver disease (ESLD), and their effects on sensitization, rejection, and liver graft survival are not well known. These effects were examined in 121 recipients of primary liver grafts, surviving > or = 30 days. Ninety-six (79%) patients received transfusions bef...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199706150-00008
更新日期:1997-06-15 00:00:00
abstract::Since 1989, the U.S. Food and Drug Administration (FDA) has encouraged the study of new drug and therapeutic products in elderly patients. However, despite the aging population in the United States, elderly patients continue to be underrepresented in clinical trials across a variety of therapeutic areas, including tra...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e31828279d9
更新日期:2013-04-15 00:00:00
abstract:BACKGROUND:Antibody-mediated rejection (AMR) remains associated with reduced kidney graft survival and no clear prognostic marker is available. METHODS:We investigated whether donor-specific antibodies (DSA) ability to bind C1q in comparison with AMR C4d status, both indirect signs of complement activation, improve ri...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000002265
更新日期:2018-11-01 00:00:00
abstract::Rapamycin prolongs allograft survival and induces donor-specific tolerance in some small animal transplant models. Large animal studies, however, are limited. We studied rapamycin in a porcine renal allograft model. Donor-recipient combinations were chosen based on high response in pretransplant MLCs. Allografts were ...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Fifty seven recipients of renal allografts initially treated with CsA and low-dose prednisone were switched to azathioprine and low-dose steroids. Ten had prolonged (greater than 28 days) allograft nonfunction after transplantation (group 1), 8 had ongoing, poorly controlled rejection (group 2), and 39 had stable func...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198412000-00024
更新日期:1984-12-01 00:00:00
abstract::The concept of islet exhaustion maintains that exposure of pancreatic islets to hyperglycemia and other stresses leads to islet dysfunction and irreparable damage. The process of pancreatic transplantation places many stresses on islets (e.g., counter-regulatory hormones, steroids, cyclosporine toxicity). As practiced...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198907000-00006
更新日期:1989-07-01 00:00:00
abstract::Murine lymphoid cells sensitized against allografts express two types of cytotoxicity measured in vitro in short-term assays of 2 to 3 hr by 51Cr release. One type of cytotoxicity is specific against target cells carrying the sensitizing alloantigens, and the other type is nonspecific against both syngeneic and unrela...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-197602000-00002
更新日期:1976-02-01 00:00:00
abstract:BACKGROUND:A new supercooling system using a variable magnetic field has been recently developed. Subzero nonfreezing preservation has been believed to be a beneficial method because of the lower metabolic rate. The purpose of this study was to evaluate the hemodynamic and metabolic effects of rat heart preservation in...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3182637054
更新日期:2012-09-15 00:00:00
abstract::High levels of tumor necrosis factor-alpha, interleukin-2, and gamma-interferon appeared in the circulation of kidney transplant recipients after the first injection of the monoclonal antibody OKT3. This initial injection was systematically followed by fever. The three cytokines were released in all patients (n = 9), ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198904000-00008
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND:Graft arterial disease (GAD) is a major cause of late graft loss after organ transplantation. Alloimmune responses and vascular remodeling eventually cause the transplant organ to develop GAD. In this study, we aimed to limit the development of GAD by inhibiting alloimmune responses and vascular smooth muscl...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000576
更新日期:2015-05-01 00:00:00
abstract::DA rats treated with cyclosporine for 2 weeks after being grafted with an RT1-incompatible PVG heart graft did not reject the graft and developed a state of specific unresponsiveness to graft antigens. The cellular mechanisms maintaining this state of unresponsiveness were studied by testing the capacity of lymphocyte...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198406000-00014
更新日期:1984-06-01 00:00:00
abstract:BACKGROUND:Human herpesvirus 6 (HHV-6) is susceptible to latency and reactivation in hematopoietic stem cell transplant (HSCT) recipients. We investigated the incidence of HHV-6 DNAemia and factors related to HHV-6 DNAemia and death after allogeneic stem cell transplantations. We also explored the relationship between ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e318289958b
更新日期:2013-05-27 00:00:00
abstract:BACKGROUND:Patients with pretransplantation strong donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) are at higher risk for rejection. We aimed to study the safety of kidney transplantation in patients with lower strength DSAs in a prospective cohort study. METHODS:Three hundred and seventy-three cons...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000191
更新日期:2014-11-27 00:00:00
abstract:BACKGROUND:Rat lung allograft rejection is mediated by collagen type V (col(V)) specific T-helper-cell 17 (Th17) cells. Adoptive transfer of these cells is sufficient to induce rejection pathology in isografts, whereas tolerance to col(V) suppresses allograft rejection. Therefore, we tested whether regulatory T cells f...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0b013e3181bcde7b
更新日期:2009-12-27 00:00:00
abstract::Since major histocompatibility (MHC) antigen matching was introduced in the early 1970s as the key factor determining kidney transplant allocation, several studies, mainly arising from organ-sharing organizations in the United States and Europe, have debated this complex issue. The first fundamental concern is the int...
journal_title:Transplantation
pub_type: 杂志文章,评审
doi:10.1097/01.tp.0000103730.16444.e7
更新日期:2004-02-27 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::Hemorrhagic cystitis is a well known complication of allogeneic bone marrow transplantation (BMT) and is normally attributed to the use of high-dose cyclophosphamide in the preparative regimen. Hemorrhagic cystitis occurring late after BMT is unlikely to be due to the effects of this conditioning, and probably has an ...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198701000-00024
更新日期:1987-01-01 00:00:00
abstract::SLT presents an interesting concept to alleviate the organ shortage for children with end-stage liver disease. The procedure has, however, not gained wide acceptance. This is not only related to the complexity of the procedure, but also to the poorer results and the complications reported on the right side graft. We r...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1995-04-27 00:00:00
abstract:BACKGROUND:Evidence on prevalence and correlates of pretransplant medication nonadherence (MNA) is limited. The present study explored self-reported prevalence and correlates of MNA before heart, liver, and lung transplantation. METHODS:This cross-sectional descriptive study included 174 patients: 69 lung, 33 heart, a...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000158430.06507.87
更新日期:2005-06-15 00:00:00
abstract:BACKGROUND:Lung transplant recipients are among those with the highest risk of influenza infection and complications each year. A few studies show adequate responses after influenza immunization; no studies examined the season-long protection. METHODS:Influenza antibody concentrations were measured using hemagglutinat...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/TP.0000000000000391
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:A pancreas transplant alone (PTA) in a nonuremic patient with brittle diabetes mellitus remains a rare procedure because the tradeoff for insulin independence is lifelong immunosuppression. METHODS:Herein we report our results at the University of Minnesota of 513 PTAs from December 17, 1966, through Decemb...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/01.tp.0000296820.46978.3f
更新日期:2008-01-15 00:00:00
abstract::Although ELISA on purified HLA molecules for detecting anti-HLA antibody (P-S ELISA) does detect some antibodies previously missed by the conventional complement dependent cytotoxicity method (C Cytotox), HLA ELISA should not fail to detect antibodies already detected by the conventional reference method to be able to...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199611270-00031
更新日期:1996-11-27 00:00:00
abstract::To investigate the causes of impaired liver function (LF)* after BMT, 88 patients were included for analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, transplant methods, preconditioning regimens, and graft-versus-host disease (GVHD). Fifty of them (56.8%) developed abnormal LF after BMT and a...
journal_title:Transplantation
pub_type: 杂志文章
doi:
更新日期:1995-04-27 00:00:00
abstract::Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin develope...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199105000-00017
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND:To define whether immunosuppressive agents that block the interleukin (IL)-2 pathway could prevent activation-induced cell death of activated T cells in the graft, we measured expression of IL-2, IL-2 receptor alpha chain (CD25), IL-15, Fas, and Fas ligand by real time reverse transcription-polymerase chain ...
journal_title:Transplantation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/01.TP.0000063937.53702.97
更新日期:2003-05-27 00:00:00
abstract::Low-affinity, cold-reactive antibodies easily removed by washing were not detected by the antiglobulin technique but killed T lymphocytes when washing was omitted, incubation was prolonged, and cytotoxic tests were incubated at room temperature or at 4 degrees C. These antibodies were present in approximately 25% of s...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-198710000-00014
更新日期:1987-10-01 00:00:00
abstract::Graft and patient survival rates after transplantation of ABO-incompatible liver allografts have been poor. We used plasmapheresis and a potent immunosuppressive regimen to control hemagglutinin levels and prevent early rejection. Ten patients who had a United Network for Organ Sharing status of 4 received ABO-incompa...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199504150-00011
更新日期:1995-04-15 00:00:00
abstract:BACKGROUND:This study evaluated zoom endoscopic findings according to four components in comparison with the histologic findings of acute cellular rejection (ACR) in a living-related small bowel transplantation (SBTx) patient. METHODS:A 16-year-old boy with microvillus inclusion disease underwent SBTx with a 150-cm-lo...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-200202270-00013
更新日期:2002-02-27 00:00:00
abstract:BACKGROUND:Pediatric liver transplant recipients have traditionally been grouped according to age. Age-based classification schemes are useful in identifying clinical problems in selected age groups and also for developing solutions to these problems. Although infants in the first 3 months of life have not traditionall...
journal_title:Transplantation
pub_type: 杂志文章
doi:10.1097/00007890-199809150-00010
更新日期:1998-09-15 00:00:00