摘要:

We have tested the effects of FK506 (FK), a new immunosuppressive agent, on a rat limb allograft model. Histoincompatible BN limb allografts were rejected in untreated F344 hosts within 11±1 days (mean ± SD) after operation. A single injection of 2 mg/kg, 10 mg/ kg, or 50 mg/kg of FK on the day of limb transplantation (day 0) significantly prolonged graft survival in a dose-dependent manner—i.e., mean limb survival times (MST) based on gross signs of skin rejection were 16±3 days, 51 ±6 days, or 104±17 days, respectively (P< 0.01). Delayed treatment with a single injection of 10 mg/kg of FK at when early signs of rejection were visible (day 7 or day 10) reversed the ongoing rejection. The MSTs in these groups were comparable to that of those treated with the same dosage of FK on day 0. The FK-induced unresponsiveness toward limb allografts was donor-specific because limb-allografted, FK-protected rats could not accept the skin grafts from a third-party donor. In the next set of experiments, rats were given a single administration of 10 mg/kg of FK on the day of limb allograft, followed by intermittent injections of 3 mg/kg of FK once a week. This regimen produced complete graft survival for more than 200 days, thoughPneumocyatis cariniipneumonia occurred in most of the recipients. These results represent the unique effects of FK in preventing or reversing the graft rejection and in inducing indefinite survival in this animal model of composite tissue allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Immunohistological studies indicate that T cells and macrophages are the major components of human kidney allograft infiltrates. Recent work has demonstrated a division of T lymphocytes into 2 subpopulations with distinct functions on the basis of their expression of the CD45R antigen (CD45R+“naive” and CD45R−“memory” T cells). This study analyzes CD45R expression on circulating T cells and T cells infiltrating renal allo-grafts in patients undergoing rejection and/or cyclosporine nephrotoxicity. The percentage of circulating T cells that expressed CD45R in patients with rejecting (63±4) or stable grafts (66±3) was not different from values obtained for normal donors (62±3). In contrast, the percentage of T cells expressing CD45R infiltrating rejecting grafts was 21±2 and was not affected by the stage of rejection; in patients with CsA toxicity the value was 22±6. The reduced proportion of T cells that expressed CD45R in the allograft may reflect a change in status from the naive state due to alloantigenic stimulation (which can be demonstrated in vitro) and/or a propensity of memory T cells to enter or be retained in an allograft.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Plasma clearances of inulin (Cin),99mTc-DTPA (CDTPA), and urographic contrast media (CCM) were determined simultaneously in 31 patients with varying levels of renal function evaluated in the setting of affiliated cardiac and renal transplantation programs. Cinand CDTPAwere calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (U×V/P). CCMwas derived from x-ray fluorescence measurement of plasma iodine (PI) content following intravenous injection of 50 ml of nonionic, low-osmolar contrast media (180 mg I/ml). Urine collections were not required for CCMdeterminations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels.CCMdetermined from the rate of decline in PI between 3 hr and 4 hr following administration of contrast media (“slope-intercept” technique) [CCM—SI] correlated closely with corresponding levels of Cin(r =.86,P< 0.0001), and CDTPA(r = 0.89,P< 0.0001). Mean CCm-SI/Cinand CCM-SI/CDTPAratios for the entire study cohort were 1.09 ± 0.06 and 1.08 ± 0.06, respectively. CCM-SI determinations also correlated well with CCMlevels derived from a single measurement of PI (“single sample” technique) made at 3 hr following injection of contrast media (r = 0.94,P< 0.0001). Both CCM-SI and CCMdetermined by the “single sample” method (CCM-3°SS) tended to overestimate Cinand CDTPA, however, when the latter were <20 ml/min/1.73 m2(mean CCM-SI/Cinand Ccm-3°SS/Cinratios 1.36±0.14 and 1.95+1.0, respectively.Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr “single sample” CCMdeterminations (r = 0.99,P< 0.0001). In addition, analysis of the variation in iodine content between duplicate specimens obtained at each of these time intervals revealed a mean ratio of 1.0±0.01 (P= NS vs. identity).Contrast clearance determination utilizing the slope-intercept method is accurate, safe, pragmatic, and more precise than serum-creatinine and endogenous-creatinine clearance for measurement of renal function in clinical transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In order to determine the relationships between allograft function and the recipient's plasma concentrations of atrial natriuretic factor (ANF), plasma ANF was measured by radioimmunoassay for 14 days after cadaveric renal transplantation in 9 patients aged 19–64 years. All received immunosuppression with prednisolone, azathioprine, and cyclosporine. No patient was in heart failure. During the study period, six grafts functioned, and three were nonfunctioning—two due to rejection and one to acute tubular necrosis.Plasma ANF concentration at the time of transplantation was 48±16 pmol/L (mean ± SEM) range 15–145 pmol/L. In the six patients with functioning grafts, ANF declined in parallel with the fall in serum creatinine (658±35 to 210±34 μmol/L). In the three with nonfunctioning grafts, serum creatinine and plasma ANF concentration both increased. There was overall a significant linear relation between serum creatinine and plasma ANF (r=0.527,P< 0.001). The changes in

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A component of the interleukin 2 receptor (IL-2R) is released in soluble form during T cell activation and can be detected in the blood during acute renal allograft rejection. This study evaluates the diagnostic utility of a sandwich enzyme immunoassay test for serum and urine IL-2R in renal allograft recipients. A rise in serum IL-2R during the week prior to the clinical diagnosis of rejection correlated better with rejection than did isolated serum IL-2R levels or urine values. For the diagnosis of acute rejection, a rise in serum IL-2R (sensitivity 73%, specificity 87%) was comparable in overall test performance to a rise in serum creatinine (sensitivity 70%, specificity 84%). Overall, the two tests had equivalent receiver operating characteristic curves. Because the etiology of false positives in creatinine and IL-2R assays differed (primarily cyclosporine toxicity and infection, respectively), the predictive value of the combined tests was superior to either alone.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

There has been concern that cyclosporine's nephrotoxicity increases the incidence of delayed graft function (DGF), prolongs periods of oliguria, and reduces graft survival. In order to further study whether CsA should be used in DGF, we conducted a randomized prospective trial of the effect of CsA versus antilymphocyte globulin on the effects of DGF. Between 12/22/85 and 3/11/88, all patients with DGF after an initial 12–24 hr of CsA were randomized to either daily Minnesota ALG and prednisone or lower-dose CsA (10 mg/kg/day) and prednisone. Resolution of DGF was defined as a lack of dialysis dependency and a 25% fall in the serum creatinine (CR). If DGF was not resolved by 2 weeks, transplant renal biopsies were performed to assess the presence of occult rejection. CsA (10 mg/kg/day) was initiated in the ALG group only after resolution of the DGF.Of the 45 patients who recovered graft function, 19 received ALG and 26 received CsA. CsA significantly prolonged the duration of DGF (ALG 9.74 days, CsA 13.69 days,P= 0.035) but did not result in a prolongation of hospitalization. No difference in CR was found between the two groups at 1 month, 3 months, 6 months, or 12 months. Mean CR at 12 months was 1.98 mg/dl for ALG versus 1.96 mg/dl for CsA. Overall graft survival did not differ in the CsA and ALG groups (P= 0.33).CsA does slightly increase the duration of DGF as compared with ALG but has no effect on one-year serum CR or one-year graft survival. Since there appeared to be no harmful long-term effects of the slight lengthening of DGF, a lower-dose of CsA protocol with biopsy surveillance for occult rejection can be used in patients with DGF.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The diagnostic efficacy of five serum liver function tests (aspartate and alanine aminotransferase, alkaline phosphatase, 5' nucleotidase, and bilirubin) was investigated in 95 bone marrow transplant recipients in whom acute graft-vs-host disease was graded by the Seattle criteria. The patient population included a control group of 22 autologous transplant recipients (group I), 33 patients with no GVHD (group II), 21 patients with grades 1 and 2 GVHD (group III), 12 patients with grade 3 GVHD (group IV), and 7 patients with grade 4 GVHD (group V). Studentttest analysis of the analytes among the five groups of patients showed that 5' nucleotidase and alkaline phosphatase were the best discriminants among all the possible combinations of group pairs. Peak levels of 5' nucleotidase within each group of patients correlated well with those of alkaline phosphatase in all the allogeneic transplant groups (II-V; r = 0.59), but the correlation of these with bilirubin was less frequent. Also, 5' nucleotidase and alkaline phosphatase showed significant discrimination (P< 0.05) even between groups I and II, suggesting that they are more sensitive than the Seattle criteria in the diagnosis of GVHD. They also showed the best overall discriminatory ability by one-factor analysis of variance (ANOVA;P= 0.0001 as compared with 0.002, 0.009, and 0.04 for aspartate aminotransferase, alanine aminotransferase, and bilirubin, respectively). Receiver-operating curves of the five analytes again revealed that 5' nucleotidase and alkaline phosphatase were by far the best discriminators among the five groups of patients. Bilirubin was relatively insensitive because it was a good discriminator only between the control group and groups IV and V. The hepatocellular enzymes, alanine and aspartate aminotransferase, correlated well (r = 0.80) but discriminated poorly among the four groups of allogeneic transplant recipients (II-V), suggesting that all four groups had some measure of hepatocellular damage that was independent of the severity of GVHD.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Improvement of graft survival after orthotopic liver transplantation is often attributed to cyclosporine. In order to assess the effects on liver function and histology, we compared the results of conventional immuno-suppression (azathioprine/prednisolone = group I) and a triple drug regimen, which included CsA (group II) during the first year after transplantation. Group I consisted of 33 patients; group II of 18 patients. Significant differences are present in favor of the CsA regimen with regard to transaminases and cholestatic parameters. Liver synthesis function was slightly better, though already very good under conventional immunosuppression. One week after transplantation, normal histology was not observed in group I, while 90% of the patients showed acute rejection. In group II, 53% of the patients showed normal histology; only 40% of the patients in group II showed acute rejection (P< 0.0002). One year after transplantation, liver histology was normal in 57% of the conventionally treated patients and in 90% of the CsA-treated patients. Also, less rejection occurred in group II during the first year after transplantation. One-year graft survival was 67% in group I and in group II 75%, which is not statistically different. Creatinine clearance did not differ in both groups. However compared with pretransplantation creatinine clearances, kidney function in the CsA-treated patients decreased with approximately 20 ml/min. These results show that liver synthesis and liver function are better under the CsA-containing triple-drug-maintenance regimen, which is supported by the far better liver histology. Kidney function is reduced, even under low dose CsA treatment.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have used sponge matrix allografts to investigate how alloantigen influences the pattern of CTL accumulation at a graft site. These studies employed two limiting dilution analysis techniques to monitor CTL accumulation. One technique quantitates the subpopulation of CTL that show evidence of in vivo contact with graft alloantigens (alloantigen-conditioned CTL or cCTL). The other quantitates all CTL with specificity for graft alloantigens, regardless of their differentiative status. Using these techniques, we have demonstrated that sponge allografts acquire three types of CTL: (a) donor-reactive CTL precursors (pCTL), (b) donor-reactive cCTL, and (c) pCTL with irrelevant antigen specificity. Sponge isografts rarely acquire LDA-detectable CTL, unless they receive a concurrent allogeneic stimulus at a distant anatomic site. In that instance, sponge isografts acquired pCTL, but not cCTL. This indicates that an ongoing immune response to alloantigens can influence the immunologic characteristics of an unrelated inflammatory response occurring elsewhere. We further observed that sponge isografts can be made to acquire alloreactive cCTL only when specific alloantigens are placed in the isograft. This indicates that specific grant

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Peripheral nerve allografting has been the subject of many experimental and clinical studies. As yet, however, no successful method has been established. One reason is the lack of detailed studies on the immune response under different conditions. We examined both the cellular and humoral immune responses in fresh sciatic nerve allografts in inbred mice, using a mixed lymphocyte culture reaction and a lymphocyte-mediated cytotoxicity to examine cellular immunity and a complement-dependent cytotoxicity test to examine humoral immunity. Enhanced MLC activity against donor allogenic major histocompatibility complex antigens was demonstrated, and specific cytotoxic T cell activity and the production of specific antigens in serum also were observed. Thus peripheral nerve tissue exhibited potent immunogenicity.We used cyclosporine, an immunosuppressive agent, to suppress the immune response and obtain favorable nerve regeneration. We performed immunologic and histologic studies to establish a causal relationship. Administration of 20 mg of CsA suppressed both the cellular and humoral immune response to levels comparable to those seen in isografting. Histologic examination disclosed favorable regeneration of axons, also comparable to that seen in isografts.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID