ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Patients who require cystectomy are usually treated with an ileal conduit or intestinal neobladder for urinary control. In some of them, however, the bowel segment cannot be used because of previous abdominal surgery or radiation treatment. Bladder transplantation from cadavers may be beneficial to these patients, if possible. To obtain basic knowledge about bladder transplantation, we developed an animal model of whole bladder transplantation in rats. Male Lewis rats weighing 270-320 g were used as both donors and recipients. Of the 23 recipients, 12 (52.2%) survived 7 days or longer after surgery. At 1 week after transplantation, the bladder showed loss of transitional epithelium and remarkable cellular infiltration. In the bladder at 5 weeks after transplantation, the transitional epithelium regenerated markedly and submucosal cellular infiltration was much improved. Regeneration of some smooth muscle cells was also noted. At 6 months after transplantation, the nerve fibers were recognized in the bladder and the volume of the transplanted bladder was well preserved (1.0-1.3 ml).This article describes an animal model of whole bladder transplantation in the rat which we produced and the results of our study. Because a large number of pure-bred animals can easily be used, we believe our rat model is very useful for basic studies of bladder transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.PVG.RT1urats develop a strong CD4 T cell-dependent alloantibody response to class I major histocompatibility complex (MHC) Aaantigen, during which CD4 T helper cells recognize and respond to Aa-derived peptides presented by recipient class II MHC (indirect allorecognition). On the basis of evidence that CD4 T cells that encounter antigen presented by resting B cells become tolerant, we have targeted synthetic Aa-derived allopeptides for in vivo presentation to class I MHC-disparate CD4 T cells by resting recipient B cells.Methods.PVG.RT1urats were treated with two peptides, P1 and P2, corresponding to the α-helical regions of Aa(residues 57-80 and 143-163), which were conjugated via an N-terminal cysteine residue to monovalent Fab fragments of OX60 monoclonal antibody, which labels membrane IgD-positive B cells.Results.RT1urats primed with free (nonconjugated) P1 or P2 emulsified in complete Freund's adjuvant produced strong peptide-specific antibody responses and a heightened anti-Aaantibody response to an Aa-disparate PVG.R8 heart graft, confirming that each peptide encompasses one or more major T cell determinant for B cell help. Pretreatment of PVG.RT1urats with a mixture of OX60-Fab-P1/P2 conjugates markedly reduced their ability to mount an Aaantibody response when challenged with either Aa-disparate blood transfusion or an Aa-disparate heart graft, although PVG.R8 heart graft survival was not prolonged.Conclusions.In this report, we show that synthetic Aa-derived allopeptides are able, when targeted for in vivo presentation to CD4 T cells by resting B cells, to impair the ability of RT1urats to mount an antibody response to Aaantigen. All subclasses of IgG anti-Aaalloantibody were profoundly reduced, suggesting that the responsible mechanism is more likely to be CD4 T helper cell unresponsiveness rather than Th1/Th2 T cell polarization.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We demonstrate here, for the first time, the mitogenic effect of insulin-like growth factor-I (IGF-I) on the development of transplant arteriosclerosis in a rat orthotopic aorta allotransplantation model (Brown Norway to Lewis).125I-IGF-I uptake by the abdominal aorta of male Brown Norway rats occurred within 30 min. Consequently, we exposed the donor abdominal aorta to 0, 200, or 500 ng/ml IGF-I at 37°C for 30 min ex vivo (n=7 per group), before transplantation. Fourteen days after transplantation, intimal thickening of the allografts in each of the three groups was 0.18±0.02 (IGF-I at 0 ng/ml), 0.23±0.03 (IGF-I at 200 ng/ml), and 0.30±0.03 (IGF-I at 500 ng/ml), respectively (mean±SEM,P<0.005 for 500 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation (cpm/μg protein) in the transplanted grafts at 7 days after transplantation (n=4 per group) was 40.6±7.6, 78.5±12.3, and 66.9±10.1, respectively (P<0.01 for 200 ng/ml vs. 0 ng/ml). [3H]thymidine incorporation in the native thoracic aorta of the recipient was 23.4±4.4. We conclude that acceleration of allograft myointimal proliferation and intimal thickening was induced directly by IGF-I.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Certain analogs of vitamin D have been shown to prevent autoimmune diseases and prolong cardiac allograft survival. We transplanted aortic allografts from DA rats to WF rats to investigate the effect of a synthetic vitamin D analog, MC1288, and cyclosporine (CsA), alone or in combination, on acute and chronic rejection (allograft arteriosclerosis) and the mechanism of action of MC1288. The histological changes in the vascular wall were quantitated as point score units (psu). Adventitial inflammation linked with acute rejection at 1 month after transplantation decreased from 10.0±0.9 psu to 4.1±1.0 psu (P<0.01) when MC1288, 0.1 μg/kg/every other day, and CsA, 5 mg/kg/day, were combined. Intimal thickening decreased from 2.5±0.3 psu to 1.1±0.4 psu (P<0.05) at 3 months after transplantation. Proliferation of the adventitial lymphoid cells, detected by bromodeoxyuridine labeling, decreased from 140±36 to 20±19 labeled cells/cross-section. MC1288 alone suppressed interleukin 2 receptor-expressing cells from 156 to 90 positive cells/cross-section. Taken together, MC1288 with CsA effectively suppress T cell proliferation and activation and decrease intimal thickening.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Transplant vascular sclerosis is expressed in transplanted human and murine hearts as a concentric intimal thickening. The purpose of this study was to characterize the location, distribution, and intensity of transplant vascular sclerosis in murine cardiac allografts using computerized morphometric analysis.Methods.Murine cardiac allograft recipients were treated with the immunosuppressant gallium nitrate to promote graft survival. The grafts were removed at 60 days after transplantation and histologically stained. The coronary arteries were analyzed for intimal thickening using a neointimal index (NI) derived with a computer imaging system.Results.A cross-section taken from the middle of a cardiac allograft showed four major coronary arteries, each with widely different NI values (65, 0, 92, and 0). The same four vessels in two other grafts also showed highly variable NI values, but different patterns of vessel involvement. Next, NI values were determined along the length of a single vessel from aorta to apex. This revealed variable, fluctuating intimal thickening along the length of the vessel. In general, arteries from the aortic versus apical regions of the grafted hearts expressed similar amounts of intimal thickening (analysis of variance,P=0.4826). Finally, a method was devised to quantitate intimal thickening from a sampling of three tissue cross-sections taken from the middle of each cardiac allograft. This value was statistically indistinguishable from values obtained by analysis of intimal thickening in multiple sections covering the entire heart (P=0.6734, 0.9021, and 0.1474).Conclusions.Intimal thickening in the coronary arteries of murine cardiac allografts appears to be variable in terms of location, distribution, and intensity. This is true for different regions of the same vessel, different vessels in the same heart region, and the same vessels in different cardiac allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Necrosis and apoptosis are different cell death mechanisms. Necrosis is a pathological process that occurs after destruction of the cell membrane. Apoptosis is a DNA-dependent cell death mechanism, which occurs under physiological and pathological conditions. Although necrosis is a well-defined phenomenon in an acute graft rejection, the occurrence and relevance of apoptosis during this process is largely unknown.Methods.The enterocyte apoptosis rates in allografted (n=24) and isografted (n=24) small intestines of the rat were compared using the in situ end-labeling technique.Results.In situ end-labeling showed a dramatically increased number of apoptotic enterocytes in allografted small intestines, whereas increased labeling could not be observed in isogeneic small intestinal grafts.Conclusions.We suggest that graft rejection-associated apoptosis, in addition to necrosis, plays an important role in the course of organ failure, and that the degree of apoptosis represents another reliable indicator for the diagnosis and prognosis of transplant rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Perforin and Fas are the two main pathways by which cytotoxic T lymphocytes (CTLs) mediate target cell lysis in vitro. The perforin pathway is predominantly used by CD8+cells, which comprise the majority of CTLs. The Fas pathway has been demonstrated to be the principal cytolytic mechanism in CD4+CTLs. CTLs have been shown to play an important role in allograft rejection. In this study, we examined the relevance of perforin and Fas to allograft rejection by transplanting pancreatic islets from fully allogeneic C3H/HeJ (C3H) or Fas-deficient C3H/lpr donors into perforin-deficient (P0) mice or controls with intact perforin genes (P2).Methods.P0 or P2 mice that were rendered diabetic with streptozotocin at 300 mg/kg i.p. received ≈350 islets obtained from C3H or C3H/lpr donors by in situ collagenase digestion and Ficoll density centrifugation of the pancreas. Four groups of animals were studied: C3H to P2 (group 1), C3H to P0 (group 2), lpr to P0 (group 3), and syngeneic P2 to P2 (group 4). Graft survival monitored by blood sugar levels was compared among the groups. At the time of rejection (blood sugar >300 mg/100 ml), grafts were harvested and analyzed by histopathology, immunocytochemistry, and reverse transcriptase-polymerase chain reaction. Primary splenic T cells of the recipients, harvested at the time of rejection, were tested for cytotoxicity against51Cr-labeled donor cells.Results.The mean graft survival for groups 1, 2, and 3 was 10.2±1.4, 12.2±6.0, and 13.2±0.8 days, respectively. Syngeneic grafts survived indefinitely. Rejecting grafts from all groups (1, 2, and 3) showed an intense infiltration by both CD4+and CD8+cells and complete islet destruction. Reverse transcriptase-polymerase chain reaction revealed granzyme B in rejecting grafts from all three groups.Conclusions.Perforin and Fas pathways alone or in combination are not required for islet rejection, suggesting that these pathways may not play a crucial role in allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Cytomegalovirus (CMV) infection represents a significant morbidity factor for transplant recipients. A rapid, sensitive, specific, and reliable test is desirable for early detection of CMV infection and for monitoring the efficacy of antiviral therapy.Methods.We examined the incidence of CMV infection in 95 cardiac and 25 renal allograft recipients followed for up to 3 years using qualitative and quantitative polymerase chain reaction (PCR) techniques. Results were subsequently correlated with clinical findings. Of the 236 samples analyzed by the CMV PCR, 84 and 20 were also analyzed by blood buffy coat culture and anti-CMV antibody IgM assays, respectively.Results.The sensitivity of the CMV PCR was found to be superior to that of the other assays, although the specificity of the blood buffy coat culture is as good as that of the CMV PCR, which is higher than that of the anti-CMV antibody IgM assay. CMV infection was detected by the CMV PCR in 17 of 95 cardiac and 9 of 25 renal transplant recipients. Clinical symptoms were observed when ≥500 copies of CMV DNA/1 μg of total DNA were detected by a quantitative CMV PCR assay using an external control CMV plasmid; however, some patients had symptoms when 50-100 copies were present. The levels of CMV DNA detected varied (50-1000 copies) in patients who developed asymptomatic CMV infection. The CMV DNA levels decreased to 50-100 copies 1-2 weeks after antiviral therapy was initiated and correlated well with disappearance of clinical symptoms. CMV DNA levels decreased to ≤5 copies at 4-7 weeks after treatment. This contrasts with patients who were unresponsive to anti-CMV therapy, in whom high levels of CMV DNA (≥500 copies) persisted for at least 5 weeks and significant levels of CMV DNA (50-100 copies) were detected for several months afterward, despite multiple courses of anti-CMV therapy. Clinical symptoms also did not disappear during this period of observation.Conclusions.(1) The CMV PCR represents a rapid, sensitive, specific, reliable test for detection of CMV infection, especially for detection of virus replication in an incipient phase. (2) The quantitative CMV PCR is useful for monitoring the efficacy of antiviral therapy to distinguish patients who respond to therapy from those who do not. (3) CMV DNA levels ≥500 copies/1 μg of total DNA analyzed by the quantitative CMV PCR can be used to differentiate CMV infection from other infections and rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued.Methods.Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions.Results.The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90±2% vs. 82±3%,P=0.020; at 5 years: 79±3% vs. 70±4%,P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins.Conclusions.Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID