摘要:

In this study we have examined the use of low-dose γ-irradiation for the reduction of islet immunogenicity in the strong allogeneic combination of WAG rat islets transplanted into diabetic AUG recipients. First, we determined that γ-irradiation reduced immunogenicity in vitro by use of a modified MLR with WAG islets as stimulators and AUG splenocytes as responders. We then determined the maximum dose of γ-irradiation that could be used (250 rads) before islet function was affected. As 250 rads islet pretreatment alone was ineffective in prolonging allograft survival, we combined the pretreatment with a short course (days 0, 1, 2; 30 mg/kg) of cyclosporine. We found that CsA was only effective in significantly prolonging allograft survival when given subcutaneously in olive oil. The CsA treatment alone gave a significantly prolonged survival time for the islet allografts (median, 37 days vs. 6 days for controls), but when combined with the 250 rads islet pretreatment a synergistic effect was seen with 100% becoming long-term survivors (>100 days). The longterm surviving AUG rats from both the CsA alone group and the CsA plus 250 rads pretreated islets group were challenged with WAG dendritic cells (DC). The islets from the 250 rads pretreated group were subsequently rejected (day 6) while the CsA alone group were not affected. The role of low dose γ-irradiation when combined with CsA treatment of islet graft recipients in inducing specific unresponsiveness will be discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Focusing on sex-difference in prolongation of allograft survival time, we have performed skin grafts between fully allogeneic rat strains, AO (RT1u) and DA (RT1a) with an immunosuppressant, cyclosporine. Isografted skins survived indefinitely, whereas allografts were severely rejected at days 7–9 without immunosup-pressive treatment. When adult male DA rats received CsA (15 mg/kg/day, i.m., for 14 days postoperatively), allogeneic skin was accepted from either male or female AO rats for 38.8±20.5 days (mean survival time [MST] ±SD) and for 44.7±43.3 days (MST±SD), respectively, with normal hair growth at around day 17. Additional CsA administration every 5 days after the initial short course treatment was also effective in preventing chronic rejection. Male AO rat skin grafted onto adult male DA rats survived for over 50 days as long as the treatment was carried out. In contrast, when adult female DA rats were used as recipients, only a few days' prolongation was observed in comparison with a non-treated group. The rejection always occurred, even during the initial course of treatment (MST±SD: 10.9±1.6 days). Younger male DA recipients, 5 and 10 weeks old, rejected AO skin within a shorter time, depending on the age. The maximal graft survival was observed when male adult rats more than 14 weeks old were used as recipients. On the other hand, the CsA serum level of female recipients at day 14 was considerably lower than that of males. However, even when the level of females was adjusted to that of males by the administration of a double dosage (30 mg/kg/day), the female recipients consistently rejected the skins (MST±SD: 14.5±1.9 days). Therefore, these results clearly indicate that this male-associated immunosuppressive effect depends upon the sex and age of the recipient animals.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Increased prostaglandin production is a possible mechanism for the immunosuppressive effects of both cyclosporine and blood transfusions. Therefore, dietary supplementation with linoleic acid, a prostaglandin precursor, combined with either modality could act synergistically.Intraabdominal cardiac allografts were performed from Buffalo rat donors to Lewis recipients. Transplant recipients received a single donor-specific transfusion, low-dose cyclosporine (CsA, 1 mg/kd/d × 7 days), dietary supplementation with linoleic acid (LA, 16% of total calories) or a combination of the three modalities. CsA, DST or LA alone significantly prolonged allograft survival. Both CsA and LA acted synergistically with DST in further prolongation of survival—however, animals receiving all three modalities achieved 100% long-term survival. Augmentation of transfusion- and cyclospor-ine-induced immunosuppression with dietary prostaglandin precursor is possible.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The UW solution developed for cold storage of the liver, pancreas, and kidney was used in a modified form in this study and tested in the orthotopic transplantation of dog livers, kidneys, and pancreases preserved for 48 hr. The modification was the alteration of the concentrations of potassium and sodium. The original UW solution contained 120 mM K+and 30 mM Na+. In this study the Na+was 140 mM and the K+only 9 mM, all other agents were identical to the original UW solution. Six of 11 dogs survived with livers preserved for 48 hr. The five deaths were due to technical complications and unrelated to preservation failure. Postoperative AST and partial thromboplastin time (PTT) values were lower (statistically significant on days 1, 3, and 4) in livers preserved in the high Na+UW solution than as previously shown in the high-k+UW solution. Other measures of liver function (bilirubin and fibrinogen) were similar between the high-Na+and high-K+groups. Six dogs survived with kidneys preserved for 48 hr in the high-Na+UW solution. The results were comparable to those obtained with the high K+solution. Four of six dogs survived for up to 28 days with pancreases preserved for 48 hr. The two deaths were due to technical complications unrelated to preservation failure. Three of the four dogs had normal blood glucose values for one month, and intravenous glucose tolerances test on day 7 and 28 were identical to those obtained in pancreases preserved with the high-K+UW solution. The high-Na+version of the UW solution appears equally or slightly more effective for 48-hr organ preservation than the original high-K+UW solution. The use of a high-Na+UW solution reduces the problems of hyperkalemic cardiac arrest in in situ flushing of the donor for multiple organ harvesting and in transplantation of the liver. Thus, with this solution livers do not need to be flushed with a low K+-containing solution prior to transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Malignant lymphoma is a frequent complication of organ transplantation. It has been suggested that such tumors arise as a result of uncontrolled proliferation of Epstein-Barr virus-infected B lymphocytes in an immunosuppressed host. Although a few cases of posttransplant lymphomas in bone marrow transplantation have been shown to be of donor cell origin, no recipients of solid-organ transplants are known to have developed lymphomas arising from donor cells. In this report, a case of diffuse high-grade lymphoma that apparently arose in the allograft of a renal transplant recipient is described. DNA fingerprinting demonstrated the tumor to be of donor origin; Epstein-Barr sequences were absent. A therapeutic trial consisting of withdrawal of immunosuppressive agents and administration of acyclovir was unsuccessful. These data support the notion that donor cells can undergo malignant transformation in solid-organ transplant recipients, and such tumors need not carry EBV genetic material.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Between January 1977 and March 1988, 10 of 892 renal transplant recipients formed urinary tract calculi posttransplantation. The presenting symptoms were predominantly those of azotemia due to obstruction and/ or hematuria. Factors predisposing to stone formation included a reconstructive urologic procedure at the time of transplantation (n=4) or a surgical complication (n=4), necessitating the placement of a ureteral stent and/or nephrostomy tube, secondary hyperparathyroid-ism (n=5), hyperuricosuria (n=4), and hypercalciuria (n=1). Four patients passed their stones spontaneously; 1 patient underwent ureterolithotomy, 3 patients underwent endourologic stone extraction, 1 patient was treated with a combination of surgical and endourologic procedures, and 1 patient underwent extracorporeal shock wave lithotripsy as monotherapy. While the management of these patients can be challenging, awareness of predisposing factors, proper application of all currently available urologic techniques, and attention to certain guidelines of management can aid in minimizing morbidity from this rare urologic complication of renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Five renal transplant recipients were observed to have recurrnt infections in association with low serum immunoglobulin levels. They have benefited from parenteral gamma globulin therapy. Following this observation, 110 renal transplant recipients were assessed; 46% had abnormal serum immunoglobulins with 4 patients identified as having monoclonal gammopathies, 8 poly-clonal gammopathies, and 39 low levels of 1 or more immunoglobulins. Those with abnormal serum immunoglobulins had been immunosuppressed longer, but maintenance immunosuppression dosage was not different from those with normal immunoglobulins. Respiratory tract infection and skin cancer were more frequent in those with low immunoglobulin levels.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The contributions of auto and IgM antibodies in the levels of serologic reactivities of 30 highly sensitized patients were assessed by autologous T cell crossmatches at 4°C and 22°C and dithiothreiotol (DTT) reduction of IgM antibodies. The range of panel reactivities of sera from these patients was 30–100%, median 55%. A monthly screen of these sera against a 30-member T cell panel was performed with and without addition of DTT (final concentration = 0.005 M). The results were divided into 3 groups. Group 1 consisted of 17 sera whose PRA values did not change following the DTT treatment. Also none of these sera had autantibodies, suggesting that these sera contained DTT-resistant (IgG) antibodies, most likely directed against allogeneic targets. Group 2 consisted of 10 sera whose PRA values declined substantially (20–42%) following the DTT treatment, but only 1 serum derived from a patient with systemic lupus erythematosus had autoantibodies. These results suggested that although these sera contained IgM and IgG antibodies, these antibodies were most likely directed at allogeneic target structures with only one exception. Group 3 consisted of 3 sera that became completely unreactive to panel lymphocytes following the DTT treatment. All 3 sera had autoantibodies that were also removed with DTT, suggesting that these sera contained predominantly IgM antibodies directed at autologous target cells. All 3 patients from whom these sera were derived received successful kidney transplants across donor-specific positive T cell crossmatches that became negative following the DTT treatment. We conclude that although 13 out of 30 patients have IgM antibodies, only a small subset of these patients have autoantibodies. Renal transplantation in the presence of auto/IgM antibodies may be safe.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Conventional staining techniques to determine the presence of tissue eosinophils underestimate their number and do not usually detect eosinophil degranulation. We have studied the involvement of eosinophils in acute renal allograft rejection by immunofluorescence localization of eosinophil granule major basic protein (MBP) in the kidney and by measurement of MBP in the plasma and urine by radioimmunoassay. Tissue eosinophilia and extracellular deposition of MBP indicative of eosinophil degranulation were observed in 94% and 87%, respectively, of patients with acute rejection as compared with 17% and 17%, respectively, of patients with cyclosporine nephrotoxicity. The urine levels of MBP were significantly elevated in acute rejection but not in cyclosporine nephrotoxicity. Plasma MBP concentrations were within the normal range in both acute rejection and cyclosporine nephrotoxicity. The presence of marked tissue eosinophilia and eosinophil degranulation did not always indicate irreversible rejection. Interleukin-2 and IL-2 receptors were also elevated in the urine during acute rejection. These results support a role for the eosinophil as an effector of tissue damage during rejection and suggest the potential usefulness of urine MBP determinations for the immunologic monitoring of transplanted patients.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In long-term renal allograft recipients on conventional immunosuppression, we have previously reported an abnormal expansion of CD3+/Leu-7+cells. These cells are large granular lymphocytes without any natural killer activity. About 20% of these CD3+/Leu-7+cells coexpress the CD4 differentiation antigen. In 65 transplant recipients at risk for more than 6 months, the mean percentage of peripheral blood CD4+/Leu-7+cells is significantly increased compared with 34 normals (5.0±0.6% versus 1.0±0.1%, P<0.0001). Patients who never received azathioprine do not show such an abnormality. We carried out this study to further define the phenotype, morphology, and function of these cells. As to phenotype, they coexpress CD2, CD3 but do not coexpress CD1, CD8, CD11, CD16, CD19, CD25, HLA-DR, Leu-M3. Morphologically, CD4+/Leu-7+cells are typical large granular lymphocytes undistinguishable from CD 16+effector NK cells. CD4+/Leu-7+cells do not exhibit any natural killer cell activity. In contrast to CD4+/ Leu-7-cells, CD4+/Leu-7+cells do not proliferate when stimulated with either lectins (Con A, PHA) or allogeneic cells. When stimulated for 3 days with PHA, sorted CD4+/Leu-7+cells do not express IL-2 receptors as detected with a PE-conjugated anti-CD25 monoclonal antibody, whereas 40% of CD4+-Leu-7-cells do so. Finally, when stimulated with PHA, CD4+-Leu-7+cells are not able to produce detectable levels of IL-2, while CD4+-Leu-7-cells do so. In long-term renal allograft recipients on conventional immunosuppression, Leu-7 antigen identifies a subset of CD4+cells that do not behave like regular T helper cells. We speculate that these cells represent an alteration in the cellular environment in transplant recipients, perhaps leading to long-term complications such as cancers and chronic viral infections.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID