摘要:

&NA;Organ culture facilitates successful transplantation of endocrine tissue in allogenic and xenogenic rodent systems. The major obstacle in applying this approach to human tissue is the difficulty in keeping adult human tissue alive in organ culture for a prolonged period. For this reason we have used an in vivo culture system that allows preservation of endocrine tissue for weeks or months. C57BL/6 (H‐2b) thyroid grafts transplanted beneath the kidney capsule of Balb/c (H‐2d) nude mice and retransplanted 15 days later to CBA (H‐2k) mice survive indefinitely without immunosuppression. We report here the use of the “interim host system” for allogenic parathyoid tissue in two patients with long‐standing hypoparathyroidism after total thyroidectomy.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;The immunosuppressive effect of the combination of a three day course of cyclosporine with one i.v. injection of 3M KCL‐extracted donor antigen or donor blood transfusion was tested across the strong histocompatibility barrier causing rejection within 8 days of kidney transplants from Buffalo (Buf, RT1b) to Wistar‐Furth (WFu, RT1u) inbred rats. Administration of 10 mg/kg/day cyclosporine alone for three days (‐1, 0, and 1) slightly prolonged graft survival time from 7 to 11 days. The combination of cyclosporine with donor Buf 3M KCl antigen or with a Buf blood transfurion administred one day prior to transplantation caused greater prolongation of graft survival—19 and 25 days, respectively. Neither third‐party BN soluble antigen nor BN blood transfustions acted synergistically with cyclosporine to prolong Buf graft survival. Increasing doses of donorsoluble antigen up to an optimal dose of 5 mg proportionately prolonged graft survival; however, administration of 10 mg antigen was less effective than 5 mg. On the other hand, administration of 1 ml of donor blood achieved the maximal effect. Lymphocytes harvested ten days after transplantation from recipients that had received combined therapy with cyclosporine and donor 3M KCl antigen not only displayed specific unresponsiveness to donor stimulator cells in mixed lymphocyte culture, but also specifically suppressed the proliferative response of syngeneic, virgin WFu responder cells to allogeneic donor Buf but not to third‐party BN cells. Furthermore, suppressor cell activity was suggested by diminished responses in an in vivo local adoptive mixed lymphocyte culture assay and by prolongation of Buf kidney survival following systemic adoptive transfer. These findings suggest that immunosuppression with cyclosporine permits induction of specific suppressor cells by 3M KCl donor antigen, resulting in specific unresponsiveness to allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;This study examined pancreatic allograft function in transplanted diabetic juvenile pigs. The grafts were transplanted with ligated, occluded (Ethibloc) or open ducts. No immunosuppression was used. Irreversible and permanent diabetes was induced by streptozotocin. Graft function was assessed by measuring glucose tolerance and insulin production during an i.v. glucose tolerance test. The fractional growth rate of the transplanted host was used to evaluate the long‐term consequence of transplantation.Normal glucose tolerance was achieved in 50%, and a slight impairment in 10% of the animals. In 35%, no detectable graft function was observed. Duct‐ligated and Ethibloc‐occluded grafts had a significantly lower function rate within the first week compared with grafts with open ducts. The fractional growth rate was significantly decreased in animals receiving grafts with occluded ducts. This was probably not due to different insulin production. No graft failures were observed within the first week in open‐duct graft transplantations. Graft failures were associated with elevated serum &agr;‐amylase and were probably due to vascular impairment. Normal glucose tolerance in transplanted pigs was associated with elevated levels of normal insulin and C‐peptide in peripheral blood, concomitant with low levels of proinsulin.Our results show that a pancreatic graft should be transplanted with open ducts. Obstructed ducts lead to an increased frequency of graft failure, while the transplanted hosts with such functioning grafts show retarded growth due to unidentified factors.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;In several combinations of inbred rats, liver allografts are spontaneously tolerated, and after a few weeks liver tolerant rats are in a state of donor‐specific transplantation tolerance. In vivo and in vitro experiments were conducted to analyze the immunological status of LEW or BN rats with spontaneously tolerated (LEWxBN) F1liver allografts several months after transplantation. Acute rejection of secondary donor‐specific heart allografts retransplanted from liver‐tolerant rats to normal syngeneic hosts suggests that the state of tolerance in liver‐tolerant rats is related to an active modification of the immune system of the rat and not to a reduced immunogenicity of the graft. No cytotoxic antibodies or cells were found in liver‐tolerant rats. Reactivity in mixed lymphocyte culture was normal or slightly reduced. Arguments for the presence of splenic suppressor cells were found in LEW tolerant rats using a local graft‐versus‐host assay, but these could not be found in BN rats, or when attempting to transfer or to break the tolerance state. A nonspecific humoral blocking factor was found in vitro in liver‐tolerant rats but transfer of serum from liver‐tolerant rats to normal syngeneic hosts did not permit a significant prolongation of donor‐specific heart allografts. These results suggest that more than one mechanism may be involved at the maintenance phase of liver allograft tolerance.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;Nineteen patients with acute rejection of a renal allograft were treated with the monoclonal antibody anti‐T12, directed against a determinant present on all postthymic T cells. Seven patients had a good response, four had an equivocal response, and eight failed to respond. Histologic studies demonstrated that the good responders had primarily cellular rejection. The nonresponders included 4 patients with moderate‐to‐severe humoral rejection, one patient with an inadequate dose of antibody, one patient who withdrew before completing the study, and one patient with late end‐stage rejection. All eleven patients with good or equivocal responses have functioning kidneys in a follow‐up of 1‐15 months (mean 7 months). Only one patient has had a subsequent acute rejection episode, which responded to a steroid pulse. No significant complications of anti‐T12 therapy occurred.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;Twenty patients who underwent uninephrectomy for kidney donation between 1964 and 1968 participated in a long‐term study of the function of the solitary kidney. Mean follow up after uninephrectomy was 15.8±.3 years. One patient with a strong family history of essential hypertension developed de novo mild hypertension. The current creatinine clearance of the donors was 80±4 ml/min. The 1‐week, 3‐6 months and 14‐18 years postuninephrectomy percentages of predonation creatinine clearance were 72±3%, 76±3% and 78±2%, respectively. The 24‐hr urine protein excretion in kidney donors was significantly higher than in controls (141±20 mg vs. 74±3 mg, respectively,P< .0005). Except for one donor who may have developed glomerulonephritis, the donors had normal urinary albumin excretion. The cause of the slightly elevated nonalbumin proteinuria is not known. However, this long‐term study of kidney donors shows no adverse effects on the blood pressure and renal function after many years of compensatory hyperfiltration.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants—and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA‐AB epitopes.As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch‐compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10‐25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;A new perfusate developed in the animal laboratory has been used in our clinical transplantation program in the last year. This perfusate provides excellent clinical results even with less‐than‐ideal kidneys, as manifested by an 83% immediate function rate and a 96.5% one‐month graft survival. Optimum utilization of all donors referred to a transplant center may lessen the problem of insufficient donor organs. Continued basic research in the laboratory to optimize perfusion preservation may produce even better perfusates that can be adapted to the clinical situation and further improve graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;We have done a comparative analysis of two consecutive clinical trials at our center: the first in 56 patients who received blood transfusions from their prospective donors (DST group), and the second in 36 patients who received such transfusions while they were taking Imuran in an attempt to reduce the incidence of sensitization against the donor (IM + DST group). The major findings of our study are: (1) Imuran significantly (P< .05) reduced the rate of sensitization from 27% to 11%; (2) Patients who had prolonged dialysis before entering one of these protocols were significantly more likely to become sensitized against their living donors, and had significantly higher sensitization against the leukocyte panel, although panel‐reactive antibodies were not significantly changed by transfusions from the live donor; (3) MLC reactivity against the living donor was not significantly altered by donor transfusions, and was also not different for sensitized and transplanted patients; (4) Results of transplantation were excellent in both patient groups, with only two grafts and two patients lost in 68 transplants (actuarial one‐year survival of 97% and 93% of patients alive and with functional grafts at one year in the DST and IM + DST groups, respectively); (5) Rejection episodes occurred in about 50% of each group, but were of a special type (DST‐type rejection) in about 30% of the DST patients and 10% of the IM + DST patients (P= .07); (6) The probability of transplantation, and the results of transplantation after unsuccessful entry into one of these protocols was not adversely affected.We think that primarily because of the low rate of sensitization the IM + DST protocol is superior to the DST protocol. Both, however, are established clinical tools that have increased our clinical transplant volume by a large number of highly successful transplants.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID

摘要:

&NA;Cyclosporine is a potent immunosuppressive drug, which has dose‐related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long‐term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty‐nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity.

ISSN:0041-1337    

出版商:OVID    

年代:1983

数据来源: OVID