摘要:

Isolated hamster islets were transplanted either into the liver via the portal vein or into the renal subcapsular space of diabetic C57BL/6J mice. The mean survival time (MST) of hamster islets cultured overnight at 37°C was 8.5±0.6 days when transplanted into the liver as compared to an MST of >21.7±4.9 days with 1 recipient still normoglycemic at 60 days when the islets were placed in the renal subcapsular space. Low-temperature culture (24°C) of the hamster islets for 7 days produced a further significant prolongation of xenograft survival when the islets were placed beneath the renal capsule (MST>43.3±4.7 days) with 2 recipients normoglycemic at 60 days. A single injection of anti-T-lymphocyte serum in conjunction with low-temperature culture did not produce a further increase in MST; however, 3 recipients were normoglycemic at 60 days. Removal of the kidney bearing successful xenografts at 60 days resulted in a rapid return to the diabetic state. It was interesting that the xenografts maintained normoglycemia in the mice at a level equivalent to the normal hamster (66.2 ± 4.7 mg/dl) instead of the nonfasting level found in normal C57BL/6J mice (128.4±6.4 mg/dl). The findings indicate that low-temperature culture of the donor islets in conjunction with using the renal capsule as the site of transplantation produced a marked prolongation of hamster islet xenograft survival. Slow rejection of the xenografts did occur in this site, and histologic studies indicated that this rejection may be antibody mediated.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The efficacy of immunosuppression including intravenous cyclosporine was assessed in a dog model of total orthotopic small bowel transplantation. Without immunosuppression, allografted animals died before the thirteenth postoperative day. Cyclosporine and prednisone therapy afforded a sixfold increase in survival of allografted animals. Bowel preparation, such as ex-vivo irradiation, treatment of the donor animal with antithymocyte globulin (ATG), or bowel preservation, did not appear to affect survival. However, a preliminary study of combination therapy using azathioprine, ATG, prednisone, and cyclosporine indicated that there were fewer early deaths as compared with other groups.Histologically, allografted bowel showed various degrees of mucosal change to which poorer nutritional aspects were attributed. “Intestinal death” caused by rejection was considered to be the principal cause of death in animals with advanced mucosal changes, in particular those who were long-term survivors. However, other debilitating factors (e.g., superimposed infection, endotoxemia, or possibly graft-versus-host reaction) may be present in nonsurvivors demonstrating fewer pathological changes in the graft.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Fourteen dogs received an orthotopically vascularized allograft of a 100-cm length of terminal ileum as a Thiry-Vella segment. Absorption, motility, myoelectrical activity and morphology of the allograft were studied to determine the most reliable indices of rejection. The earliest histological evidence of rejection occurred at a mean of 6.2±0.9 days and was coincident with significant deterioration in the absorption of water, alanine, lauric acid, sodium, and glucose. Intestinal motility did not decrease until 7–8 days after transplantation, and intestinal myoelectrical activity was unchanged for a further 2–3 days, by which time graft necrosis was imminent.Reduced intestinal motility occurs only after rejection is established, and is therefore of little use as an index of rejection, while recording intestinal myoelectrical activity is valueless and serves only to confirm graft death. Decreased intestinal absorption of water, sodium, glucose, alanine, and lauric acid are present as early as the first changes in mucosal histology and are useful indices of rejection of intestinal allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Terminal ileum was autografted (24 dogs) or allografted (18 dogs) as a 100-cm Thiry-Vella segment, and absorption, motility, and histology were studied. Dogs with allografts were given cyclosporine (CsA) 20 mg/kg/day. At a second operation 5 to 6 weeks after transplantation continuity of the nontransplanted intestine with the Thiry-Vella segment was restored. At a third operation 3 months after autografting, all the non-transplanted small intestine was excised.All technically successful autografts survived indefinitely, and the dogs weights were maintained at 88 ± 0.6% (mean ± SE) of preoperative weights by absorption from the autografted intestine. Administration of cyclosporine to dogs with intestinal autografts produced a reversible impairment of intestinal absorption.Dogs with allografts survived 63.3±15.5 days (mean ± SE). Death within 9 weeks of transplantation was from peritonitis secondary to graft rejection. Death in long survivors was a consequence of inadequate intestinal absorption. In the first 4 weeks after transplantation absorption and motility of allografted Thiry-Vella segments was comparable to the intestinal autografts but allografts showed evidence of a protein losing enteropathy. Large volumes of high protein—content fluid were lost from the allografted Thiry-Vella segments, and dogs with allografts became hypoalbuminemic.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

In this study, 15-deoxyspergualin (DSG) or cyclosporine (CsA) was administered to heterotopically heartgrafted rats for 15 days, commencing on the day of transplantation. In addition, a31P nuclear magnetic resonance (NMR) technique was applied to investigate the in vivo energy metabolism of the graft. A significant prolongation of graft survival was observed in groups treated with 2.5 mg/kg and 5 mg/kg of DSG, when compared with the control group not treated with an immunosuppressant. One graft in the DSG 2.5 mg/kg-treated group and one in the 5 mg/kg-treated group survived for more than 100 days after grafting. The31P NMR study demonstrated that, although rejection occurred in the rats treated with 2.5 mg/kg of DSG during the early period after transplantation, 5 mg/kg of DSG inhibited rejection completely. As for CsA, while 2 mg/kg of the drug did not affect graft survival, 5 mg/kg and 14 mg/kg significantly prolonged survival. It was revealed by31P NMR, however, that CsA 5 mg/kg did not quite inhibit rejection by itself, and 14 mg/kg of CsA, which was the tolerogenic dose, exerted a cardiotoxic effect. In consequence, DSG seems to be a powerful immunosuppressant with a low toxic effect.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We have established a murine model of syngeneic bone marrow transplantation based on the use of monoclonal antibody as the sole conditioning regimen in unirradiated recipients. Administration of a single injection of monoclonal antibody directed against major histocompatibility complex-encoded class I determinants facilitated permanent hemopoietic stem cell engraftment without any apparent side-effects. Whereas untreated hosts exhibited a maximal chimerism of 15% at donor cell doses of up to 12x10 bone marrow cells, pretreatment by 2 mg of anti-class I antibody one week prior to transplantation of 3x10 syngeneic bone marrow cells resulted in a mean donor representation of about 80%. The antibody can be given up to four weeks prior to transplantation, and the degree of donor engraftment observed is a function of the dose of antibody administered. The fact that specific antibody enhanced engraftment in two strain combinations indicates that antibody is the active agent in facilitating engraftment and that facilitation is not strain-restricted. Anti-class I antibodies of the IgG2a, but not IgG1, isotype are effective in promoting engraftment. Although the isotype requirement suggests a role for antibody-mediated cytotoxicity in promoting stem cell engraftment, the extensive time-frame of facilitation suggests that other effects of the antibody may also be involved.The model of syngeneic bone marrow transplantation we describe here will be useful in studying the mechanisms regulating stem cell engraftment and may have potential clinical application as an approach to autologous marrow transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Chronic, stable mixed chimerism of both lymphocytes and erythrocytes was observed in semiallogeneic murine recipients of T-cell-depleted bone marrow transplants that had been conditioned with supralethal total-body irradiation (1100 cGy). Mixed chimerism was extensive, with a wide range of donor engraftment persisting for at least one year after transplant. In both erythrocyte and lymphocyte lineages, decreasing donor engraftment correlated with decreasing marrow dose; however, complete red cell engraftment was more easily achieved than complete lymphocyte engraftment. There were no late graft failures, even among animals exhibiting a substantial host component of hematopoiesis. The extent of mixed hematopoietic chimerism therefore appears to be much greater than had been expected in recipients of T-cell-depleted bone marrow transplants.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We have investigated the immunogenic potential of rat heart vascular endothelial cells by their ability to induce an accelerated rejection of a relevant heart allograft, and related the immunogenic potential to the expression of class II major histocompatibility complex (MHC) antigens on the endothelial cell surface. Only 12% of freshly isolated rat vascular endothelial cells express class II antigens in serum-free medium, and the level of expression is low as judged by immunoperoxidase staining and/or the ability of endothelial cells to bind staphylococci to the cell surface after treatment with monoclonal antibodies to the class II molecule. On the other hand, 99% of the endothelial cells under the same conditions express class I, and the level of expression is high. The class II antigen expression of vascular endothelial cells can be upregulated to more than 98% by recombinant gamma-interferon in vitro—and, con

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Forty-five patients at high risk for cytomegalovirus (CMV) infection were studied during the first 100 days after marrow transplant to determine the relationship between cytotoxicity against CMV-infected HLA-mismatched target cells and CMV infection. Peripheral blood lymphocytes (PBL) from 35 patients who developed CMV infection had significantly lower cytotoxicity against CMV-infected targets 20–40 days transplant compared with PBL from normal controls (P=0.003). Responses by PBL from 10 uninfected transplant recipients were not significantly decreased. The PBL that lysed CMV targets had phenotypic and Erosetting characteristics consistent with natural killer cells. Cytotoxicity against CMV-infected targets by PBL from patients with acute graft-versus-host disease (GVHD) was reduced 20–40 days after transplant compared with responses by patients without GVHD (P=0.04). Survival from CMV infection was longer in patients whose PBL had >15% lysis of CMV-infected targets during the first 20–60 days after transplant (P=0.04). This study suggests that natural cytotoxicity of CMV targets is an important correlate of the acquisition and outcome of CMV infection after marrow transplant.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Characteristics of the sensitization response to donorspecific transfusion (DST) have been studied in the context of the pretransfusion panel reactive antibody (PRA) status of the recipient. Two distinct patterns of response to DST and Imuran treatment have been found. In patients with one-haplotype-matched donors, the panel nonreactive patient (PRA <10%) has a 19% incidence of DST sensitization that is further reduced by Imuran treatment to 6%; antibodies are both anti-T cell and anti-B cell, are transient, and are specific to the mismatched HLA antigens of the blood donor. Panel-reactive patients (PRA >10%) have a 56% incidence of DST sensitization; the antibodies appear within 2 weeks of the first transfusion, are anti-T cell, and are generally of broad specificity and persistent duration consistent with amplification of a previous antigenic exposure; Imuran seems to have little or no effect in reducing the incidence of sensitization in these panel-reactive patients. However, panel reactive patients whose PRA levels spontaneously fall to panel-nonreactive levels immediately prior to DST therapy have an exceedingly low (0–8%) incidence of sensitization with or without Imuran coverage.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID