摘要:

The effects of preoperative donor-specific blood transfusion (DSBT) on the physiologic, morphologic, and immunologic aspects of aspects of allograft responsiveness were evaluated in a rat renal transplant model, using the ACI (RT1a) into PVG (RT1c) high-responder strain combination. Indefinite graft survival (mean >63 days) could be induced by DSBT administration alone. In comparison, animals receiving autolgous blood transfusion (ABT) all died within 7 days posttransplantation. As assessed by clearance of inulin and paraaminohippurate, renal allograft function in DSBT-pretreated recipients at 6 days was equivalent to that of isograft recipients, and in contrast to the significant reduction seen in ABT treated rats. Likewise, thromboxane B2(TXB2) production by ex-vivo-perfused allografts from DSBT-treated recipients was comparable to that of isografts, and significantly lower than that of allografts from ABT-treated rats. A significant inverse correlation was found between renal TXB2production and inulin clearance. Despite these substantial differences in renal function and eicosanoid metabolism, morphologic evaluation of renal allografts from DSBT-enhanced and ABT-rejecting recipients at comparable time points showed equivalent histologic manifestations of rejection. In addition, immunohistologic labeling of renal allograft sections and fluorescence-activated cell sorter analysis of cells eluted from allografts showed the same phenotype and pattern of infiltrating T cell subsets in both groups. Specific antidonor cytotoxic T lymphocyte precursor (pCTL) frequencies of cells eluted from kidney grafts were equivalent in DSBT and ABT-pretreated animals, and both groups expressed significantly higher (but equivalent) pCTL frequencies in the kidneys than spleens. Comparisons of the lysis of PVG.R1 (RT1.Aaon a PVG background) and ACI targets indicated that cytotoxic responses from effector cells freshly eluted from DSBT and ABT kidneys were primarily directed against allogeneic class I major histocompatibility complex (MHC) specificities, whereas several long term T cell lines generated from 6-day kidney transplants of both groups expressed a predominant W3/25+(T helper) phenotype and cytotoxic activity against donor specificites other than RT1.Aaclass I MHC. Specific antidonor proliferative T lymphocyte (pPTL) precursor frequencies of cells eluted from renal allografts were also equivalent for both DSBT- and ABT-treated recipients, and the range of pPTL frequencies for allograft cell eluates was similar to that in spleens, regardless of the source of the transfusion. Thus, in the rat, the prolonged renal allograft survival seen with DSBT pretreatment is associatated with reduced thromboxane production, and does not appear to involve early depletion of alloreactive cytotoxic or proliferative T cell clones or activity. Moreover, these findings suggest that the presence of significant alloreactive cytotoxic and helper T cell populations within the spleen and allograft itself does not necessarily result in renal transplant dysfunction or rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The hypothesis tested in the present and accompanying study is that and effective treatment for severe burns involves early excision of necrotic tissute followed by skin allografting ad cylosporine (CsA) immunosuppressive therapy. LEW (RR11) rats served as recipients of thermal injury and/or skin allografts. BNxLEW F1M(LBN, RT11+n) rats served as skin donors. LEW burn recipients received a hot water (90oC for 10 sec) 30% body surface area (BSA) full-thickness burn. As expected, LEW recipients treated with CsA (25 mg/kg/day for 20 days) demonstrated singnificant graft polongation compared with controls (P<0.005). Skin graft survival was similarly prolonged in LEW recipeints undergoing burn unjury, primary wound excision, and CsA administration comkpared with not increased in the thermal injury—CsA-treated recipients comkpared with burn controls. A final experiment was initiated to investigate how low-level long-term (>100 days) maintenace CsA treatment influenced skin allograft survivalfor possible future consideration in burn trauma. Recipioents receiving skin allografts plus CsA (20 days, 8mg/kg/day, followed by every other day therafter) did not reject their grafts. However, a possible early sign of rejection ( a gingle small ulceratiove lesion) was noted in five of these long-term CsA-treated animals at a meanof 3411 (SD) days. The lesion in these animals did not progress any further during CsA administration. His-topathologic study of selected animals removed from the CsA maintenance regimen for greter than 50 days following long-term administration revealed a number of interesting chronic lesions similar to thosse previously reported in the skin comonent of composite tissue (limb) allografts following long-term low-level CsA intervention. In conclusion, CsA was very successful in preventing rejection of skin allografts in a rat burn model without apparent adverse effects.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We have previously reported the successful treatment and apparent development of skin allograft tlerance in a patient sustaining massive burns, utilizing skin allowgrafts and cyclosporine. We now report the experimental correlate cia successful achievement of a 75% body surface area (BSA) scald burn cyclosporaine—skin allograft model in Lewis (LEW) rats. Cyclosporaine (8 mg/ kg/day) was given to the experimental animals daily for the first 20 days and then three times a week therafter. Two experimental groups were studied: one reveived stadard posttrauma care and the second critical posttrauma care. Controls (n=22) and experimental groups 1 (n=28) and 2 (n=4) had average survival time sof 13.812.8 days, 44.2132.5 days, and 172.019.4 days, respectively. The allografts on the surviving experimental animals appeared normal and healthy and had nealy perfect hair growth. These results indicate that the model follows the clinical burn wound course, and treatment of massive burns with primary excision, skin allografts, and low doses of cyclosporine could provide immediate and complete functional repair of the burn wound.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy was used to serially evaluate heterotopic renal allograft rejction in the rat. Renal allografts transplanted to the groin of recipient animals were studied using a 1.89 Tesla horizontal bore magnet. The relative intracellular concentrations of phosphorus metabloities such as adenosine triphosphite and inorganic phosphate as well as intracellular pH were determined by31P NMR on days 4, 7, 10, and 14 following transplantation across a major histocompatibility mismatch. Recipient rats chossen to be rejectors received no immunosuppression while animals chose to be nonrejectors recieved cyclosporine during the first 7 days following transplantation. By day 7, all rejector rats could be distinguished from nonrejector rats by their higher relative concentration of inorganic phosphate and their lower relative concentration of adenosine triphosphate. These NMR findings correlated with histologic findings of renal infarction probable related to vascular rejection in the allografts.31P NMR spectroscopy may have application as a noninvasive tool in the differential diagnosis of posttransplantation renal insuffieciencey.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Procedures for successful autologous and MHC-matched allogeneic bone marrow transplantation in partially inbred, MHC-defined miniature swine have been established. All marrow recipients were conditioned with single-dose total-body irradiation at the upper level of tolerance, and supported with antibiotics and irradiated blood products during aplasia. Surgical harvest of autologous and allogeneic marrow yielded sufficient numbers of cells to successfully reocnstitute recipients. Radiation control animals that reveived no marrow failed to show recovery of marrow function. Pigs transplanted with autologous marrow at dosed greater than108cells/kg/ routinely engrafted and recovered normal marrow function. The major clinical complications were acute and chronic infections and hemorrhage. T cell-depleted autologous marrow also engrafted, and there was no observed increase in clinical complications. In bone marrow transplantation across non-MHC allogeneic differences, engraftment and survival were similar

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In order to stusy the effct of defined genetic differences of one bone marrow transplantation in miniature swain, five different conninations of major histocompatibility complex (MHC)-matched adn mismatched bone marrow transplants were perfomed. Eight of nine fully MHC-mismatched allogeneic bone a marrow transplants faile to reconstitute, and one animal reconstituted briefly but then died quickly therafter. Five of six class I-matched/class II-mismatched (gc) bone marrow transplants engrafted, showed a skin rash trypical of graft-versus-host (GVH) reaction, and died 3 weeks after the marrow transplants into F1hosts engrafted and caused GVH skin rash, with survivals from 1 to 9 montsh (n=5). Serologica typint of the F1recipients of parental marrow showed only donor-type peripheral blood lymphocytes (PBL), suggesting complete marrow replacemetnt. Conversely, F1into parental marrow transplants showed no engraftment (n=6).These results indicate that resistance to MHC-mismatched allogeneic bone marrow engraftment donor class I MHC differences. This response appears to interfere with engraftment of donor bone marrow cells despionte host preparation with 900–1100 rads total-body irradiation. In the absebce of donor MHC class IO differences, engraftment was seen despite the existence of multiple non-MHC differences, and even in the presence of class II differeces. Such engraftment also led to GVH, varying in intensity according to the strength of genetic disparioty (i.e., worst in parentF1combination). Thses results suggest that miniature swaine should proviode adn effective model for study of both GVH elimination (in the parentF1combination) and problems of engraftment (in the F1parent combination), the two most important obstacles to clinical allogeneic transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Brain-dead organ donors are depleted of circulating triiodothyronine (T3) and show features suggestive generally of anerobic metabolism at the tissue level, accompained by derteriorating hemodynamic function. The principle of single-bolus kinetics with labeled carbon compounds (14C-R), with subsequencet measurement of both plasm activity an dof exhaled14C O2has therefore been used to study glucose, pyruvate, and palmitate utilization under conditions of (1) sedation, (2) brain death, and (3) brain death with T3therapy in the baboon. Serum lactate and plasma-free fatty acid concetrations were also measured. There was a major change in metabolic oxiodative processes folowing brin death. The rate of glucose, pyruvate, and palmitate untilization was markeldy reduced, and there was an accumulation of lactate and free fatty acids in th plasma, indicating a general change from aerobic to anerobic metabolism. The administration of T3to th brain-dead baboon resulted in a dramatic increase in the rate of metabolite utilization, and a reduction in the plasma conctrations of plasma lactate and free fatty acids, indicating an apparent reversal from tissue anaerobic to aerobic metabolism. We suggest that T3should be adminstered to all brain-dead potential ortgan donors to correct and maintain a more physiologic metabolic status and thus to improve oragan function.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

This report examines the effect of pretransplant (pre-Tx) blood transfusions (BT) on the patioent and graft survival results of 320 cyclosporine (CsA) and prednisone (Pred)—treated primary (10) recipients of cadaveric (CAD) donor renal allografts. The 320 CsA-Pred treated 10) -CAD recipients included 100 pre-Tx untransfused (O-BT) and 220 transfused patients. The overall patient survivals at 12, 24, adn 36 months post-Tx were 94%, 94%, adn 93%, respectively. There were no differences observed in graft survivals at 12, 24, or 36 months post-Tx wherther patients received 0, 1–4,5–10 or> 10 pre-Tx BTs. A mean serum creatinine of 1.90.7 mg/dl was comparable among all BT groups at 12, 24, and 36 months post-Tx. The frequency of rejection eposodes—namely, 37% for O-BT and 36% for >O-BT were identical. High-riosk patients (>45 years of age, diabetics, or blacks) were comparably distributed in O-BT and >O-BT groups and did not impact on the data. Similarly, increasing panel-reactive antiobodies (PRA), associated with increasing numbers of pre-Tx BTs, did not influence the data. When HLA A, B, and DR matching results were combined with the BT groupings no difference were observed in patient or graft survivals. Poorly matched and untransfused recipients. These findings suggest that CsA-Pred immunosuppressive therapy allows for successful 1o-CAD renal allograft transplantation without the need for pretranplant blood transfusion conditioning or matching of donor HLA A, B, and DR antigens to recipients.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The results of kidney retransplantation in the cyclosporine era remain to be determined. Over a 42-month period, 76 nonprimary renal transplants (66 second, 7 third, 3 fourth allografts) were performed in 73 recipients under cyclosporine immunosuppression. The patioent population was predominantly white (90.4%) with a mean age of 32.3 years. Twenty-one recipients (28.8%) were diabetic, and 36 (49.3%) were highly ssensitized (panel-reactive antibody [PRA]>50%). Sioxty-two patients received cadaver donor grafts while the remaining donations were living-related (12) or living-unrelated (2). A sequential antilymphocyte globulin/cyclosporine protocol was employed, with cyclosporaine therapy delayed until adequate renal function occurred.Overall patient and grafts survival is 92.1% and 60.5%, respectively, after a mean follow-up of 20.0 months. The mean serum creatinine is 1.64 mg/dl in the 46 functioning allografts. Graft survival is 63.6% for secondary grafts, 28.6% for tertiary grafts, and 66.7% for fourth kidney transplants. In ssecond transplants, reciopients of cadaver donor kidneys have a graft survival of 58.5%, while living-related donor graft survival is 84.6% (P=0.07). In the cadaver retransplant population, duration of previous transplant function greater than one year adn HLA-DR matching were associated with increased graft survival, while age over 39 and presence of diabetes mellitus with reduced graft survival. However, these trends were not significant. Peak

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

In this study, we analyzed the incidence of complications and clinical results of 57 patients who received kidney transplants at our institution and survived with a functioning allograft for 10 years or longer. All patients recieved their care at our center and their clinical and laboratory data were monitored routinely at minimum monthly intervals.In this second decade, during a mean follow-up of 2.82.2 years (range 0.4–7.8 years), 7 patients suffered graft loss (chronic rejection 6; irreversible acute tubular necrosis from aminoglyucosides 1) and 7 others died with a functioning allograft (causes: hepatic failure 2, seposis 2, malignancy 2, and cardiac infarction 1). The cumulative patient survival was 96% at 11 years and 85% at 15 years. The corresponding graft survival rate was 92% at 11 years adn 71% at 15 years. Of the 43 patients currently rehabilitated, and 1 is medically disabled. The complications observed were: infection in 25 patients (44%), hypertension in 24 (42%), hyperlipidemia in 23 (40%), liver disease, 22 (39%) musculoskeletal problems in 21 (37%), cataracts in 19 (33%), rejcetion in 15 (26%), malignancy in 9 (16%), vascular occlusive disease in 9 (16%), gastrointestinal disorders in 9 (16%), adn other problems no included in the above categories in 26 (46%).Our observations suggest that renal transplant recipients experience significant mortality even in the second decade. Continued medical follow-up is therefore essential for an early diagnosis and management of these late complications. Measures directed at prevention and therapy of these late complications may further enhance the long-term success rate of renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1988

数据来源: OVID