摘要:

Pancreatectomized dogs received intrasplenic auto-transplants or allotransplants of unpurified islets prepared from the pancreata of unrelated outbred dogs, by a standard collagenase ductal perfusion method. Allograft immunosuppression consisted of tapering azathioprine-prednisone (AP), low level cyclosporine (CsA, through whole blood high-pressure liquid chromatography (HPLC) level 300–600 μg/L), or high CsA (600–1000 μg/L). While AP and low CsA failed to delay rejection, high CsA achieved prolonged (>100 days) graft function in 5 of 12 dogs, with a median duration of 85.5 days. (P<.01 vs. AP and low CsA). While no interference with islet engraftment was seen in CsA-treated dogs, late graft failure (>30 days) was seen in 3 of 6 CsA autografts and 5 of 12 high CsA allografts. CsA at whole-blood HPLC levels of 600–1000 μg/L can achieve prolonged normoglycemia in pancreatectomized canine recipients of islet allografts. The effects of such doses of CsA on islet function may be substantial.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Arterial and/or venous thrombosis is a frequent complication in experimental or human pancreatic transplantation. A canine experiment was used to study the hemodynamic effects of spleno-splenic arteriovenous fistula during segmental pancreatic transplantation. An increase in blood flow, without “steal” syndrome in the pancreatic blood supply or preasure increase, was found. Thus this technique can help prevent vascular thrombosis in pancreatic transplant in dogs.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Improved viability and function of insulin-producing beta (B) cells of frozen-stored human fetal pancreatic tissue was obtained by a two-step method utilizing high concentrations of dimethyl sulfoxide (DMSO). Human fetal pancreata (14–23–week gestation) obtained from pathologic abortions were teased and cultured overnight. Prior to freezing the tissues were immersed in 0.9% saline containing 0.5 M DMSO for 30 min (room temperature) and then placed in 2.1M DMSO on ice for 5 min. The tissues were frozen by the method previously developed in our laboratory and stored at – 196°C. The frozen-stored tissues were subsequently thawed at 24°C and cultured overnight before viability testing. Viability and function of the B cells were assessed by several specific assay methods; glucose plus theophylline-induced insulin release during static incubation and perifusion,3H-leucine incorporation into insulin, and insulin content of the tissue grown in athymic mice for 7 days.The response to glucose plus theophylline stimulation, measured on the frozen-thawed tissue one day after thawing, was 80% of the level measured in control tissue maintained in organ culture. Frozen-thawed tissues maintained in organ culture for 1 week responded comparably in the in vitro assay systems. The insulin content of frozen-thawed pancreatic tissue removed from athymic mice 1 week after transplantation was approximately 60% of the amount measured in the control grafts. These results demonstrate the utility of our procedure in the maintenance of the viability and function of frozen-stored human B cells both in culture and after transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Past studies in dogs have suggested that marrow graft rejection was mediated by major histocompatibility complex (MHC) class II antigen–positive non-T cells that survived standard doses of total-body irradiation (TBI). We have now raised 4 monoclonal antibodies (mAbs) against marrow cells harvested 6 days after TBI. The mAbs are highly reactive (>70%) with marrow cells surviving radiation and also bind strongly (>50%) to normal marrow cells, lymphocytes, monocytes, and granulocytes. One of the mAbs (34-S3) reacted strongly with NK-like cells. In vitro treatment of marrow with mAb and rabbit complement (C‘) did not affect erythroid colony-forming unit (CFU-E) growth, whereas 2 of the 4 mAbs inhibited granulocyte-macrophage colony-forming unit (CFU-GM) growth, and all 3 mAbs tested suppressed autologous marrow engraftment. One of the mAbs, 69-S5 (IgG1), bound to a 95,000 dalton antigen. It crossreacted with human cells, but not with cells from Rhesus monkeys, baboons, and cats. We administered this mAb intravenously at 0.2 mg/kg/day on days −5 to 0 to dogs given 9.2 Gy TBI on day 0 followed by marrow grafts (≤4 × 108cells/kg) from DLA-nonidentical unrelated donors. Three of five dogs had sustained grafts. Increasing the dose of mAb ten-fold (2 mg/kg/day) resulted in graft failure (2 of 2 dogs). Treatment with a dose of 0.2 mg/kg/day from day −7 to −2 showed sustained engraftment in 7 of 10 dogs. This result is in contrast to sustained grafts in 3 of 36 dogs not given mAb, and in 1 of 7 dogs treated with an irrelevant mAb (P=0.0002 and 0.04, respectively). We conclude that treatment of recipients with a mAb raised against marrow cells surviving radiation and not directed at major histocompatibility complex (MHC) class II antigens and …

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Spleens of fetal/newborn mice less than 3–4 days of age contain a naturally occurring cell population capable of suppressing T-dependent and T-independent immune responses of third-party adult cells both in vitro and in vivo. We have utilized newborn spleen cells to prevent acute graft-versus-host (GVH) disease in lethally irradiated adult hosts reconstituted with semiallogeneic or even allogeneic bone marrow cells. Pretreatment of reconstituting cell populations with newborn spleen cells reduced the incidence of GVH disease from 100% to 20% in semiallogeneic and from 100% to 40% in allogeneic combinations. Long-term-surviving reconstituted hosts proved immunologically unresponsive to both donor and host histocompatibility antigens, yet possessed a fully chimeric lymphoid system responsive to T and B cell mitogens, as well as unrelated third-party alloantigens.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Recipient dogs were conditioned with 9.2 Gy of total-body irradiation followed by the infusion of bone marrow and peripheral blood leukocytes from a DLA-haploidentical litter mate (N=1O) or a completely allogeneic unrelated donor (n=9). Graft-vs.-host disease (GVHD) prophylaxis consisted of methotrexate (MTX) and cyclosporine (CsA). Postgrafting all dogs were complete lymphohemopoietic chimeras. Lymphocytes of haploidentical chimeras without GVHD were unresponsive to stimulation by host lymphocytes cryopreserved pregrafting. Lymphocytes of haploidentical chimeras with GVHD proliferated in response to host cells, albeit less than donor cells pregrafting. In completely allogeneic chimeras, neither lymphocytes from dogs with GVHD, nor those from dogs without the disease showed responses to host lymphocytes. In addition, cells from haploidentical chimeras obtained early after transplantation non-specifically suppressed donor cell proliferation. Later on, lymphocytes from dogs without GVHD showed specific suppression of donor cells, while lymphocytes from chimeras with GVHD continued to show nonspecific suppression. Cells from completely allogeneic chimeras both with and without GVHD never suppressed donor cells specifically. Both specific and nonspecific suppressor cells were enriched by nylon wool adherence, expressed T cell markers, and were not affected by the addition of indomethacin. Even after removing nylon wool—adherent cells, however, chimera cells were unresponsive to stimulation by host cells. By one year after transplant, chimera lymphocytes no longer showed suppression. In cell-mediated lympholysis assays, lymphocytes from all chimeras, regardless of GVHD, failed to generate cytotoxic cells against host cell targets. However, while haploidentical chimeras showed cytotoxicity against third-party targets, completely allogeneic chimeras did not. This deficiency was not overcome by the addition of mixed leukocyte culture supernatant or donor lymphocytes. All chimeras had basically normal antibody responses to keyhole limpet hemocyanin and phage X174. However, while haploidentical chimeras had normal responses to bacillus Calnette-Guerin (BCG) sensitization and rejected DLA-incompatible skin grafts within the normal time frame, completely allogeneic chimeras were not sensitized by BCG and showed delayed skin graft rejection. Histopathological studies revealed slow thymic reconstitution in all chimeras, particularly in the presence of GVHD. However, while healthy haploidentical chimeras eventually showed thymic histology normal for age, completely allogeneic chimeras did not. In agreement with previous studies, these data are compatible with the notion that clonal abortion is involved in the development of tolerance. In addition, different patterns of alloreactivity are associated with the presence of specific or nonspecific suppressor cells. While haploidentical chimeras become immunocompetent, major defects of cellular immunity persist in completely allogeneic chimeras.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologie data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Cytomegalovirus is present in a latent state in renal allografts and may be reactivated in recipients. While human and murine strains are alike in that a primary infection occurs in seronegative recipients of a kidney from a seropositive donor, they may differ when the recipient is seropositive. In a murine transplant model, superinfection of a seropositive recipient with a second strain is unusual. Reports in human transplantation indicate that superinfection of a seropositive recipient does occur, however the frequency is unknown.Our studies examine the potential importance of specific viral strains in host and recipient, the contribution of prior humoral immunity in the recipient, and the technical ability to identify distinctive strains of virus in the presence of each other.Our results indicate that reversal of the viral strains in donor or recipient animals does not alter our previous observation that reactivation of the endogenous recipient viral strain predominates as the infecting strain in the posttransplant period. Further, the presence of antibody in nearly all donors and recipients confirms that all animals were originally infected prior to transplantation. Finally, we demonstrated the technical ability to detect one virus in the presence of the other, thus excluding this variable as possibly confounding.We conclude that the endogenous, latent recipient strain of cytomegalovirus in the murine model is preferentially reactivated in the posttransplant interval.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Previous epidemiologic studies of hypertension in renal transplant patients have produced contradictory results. Therefore, the incidence and clinical setting of chronic hypertension were examined in 201 stable renal transplant patients using a multivariate approach. Hypertension was present in 52.7% of patients at one year, and in 46.3% at the time of last follow-up, 5.0±1.9 years (mean ± SD) after transplantation. Among possible causative factors, discriminant analysis demonstrated that body weight, the presence of native kidneys, and variables linked to allograft function were most closely associated with hypertension at both one year and last follow-up. One year after transplantation, age, sex, pre-transplant hypertensive nephrosclerosis, and diabetes were also independently associated with hypertension. However, renal function declined to a greater degree in hypertensive patients, and only body weight, the presence of native kidneys, and variables linked to allograft function were associated with hypertension at last follow-up. Results also demonstrated that hypertension was associated with elevated serum lipid levels and an increased likelihood of dying or returning to dialysis. Thus, these results suggested several important risk factors for hypertension and its consequences in renal transplant patients.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Lymphoid cell engraftment was monitored for several years after bone marrow transplantation by Y-chromatin staining of T and B lymphocytes in the peripheral blood and/or by immunoglobulin allotyping in the serum of 20 of 52 pediatrie patients grafted successively between October 1973 and October 1983. Data on 2 patients with severe combined immunodeficiency, grafted earlier in December 1968 and April 1971, are also included. These children received an allogeneic bone marrow graft for leukemia (n=7), severe aplastic anemia (n=11), or severe combined immunodeficiency (n=4) and were informative for this study, because they differed from their donor by sex (n=16) and/or by immunoglobulin phenotype (n=13).

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID