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排序方式: 共有676条查询结果,搜索用时 15 毫秒
1.
The pathology of posttransplant lymphoproliferative disorders occurring in the setting of cyclosporine A-prednisone immunosuppression. 总被引:26,自引:7,他引:26
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M. A. Nalesnik R. Jaffe T. E. Starzl A. J. Demetris K. Porter J. A. Burnham L. Makowka M. Ho J. Locker 《The American journal of pathology》1988,133(1):173-192
Posttransplant lymphoproliferative disorders (PTLDs) were diagnosed in 43 patients from the Pittsburgh-Denver series between June 1980 and March 1987. This constitutes a detection rate of 1.7%. Major categories of clinical presentation included a mononucleosislike syndrome, gastrointestinal/abdominal disease, and solid organ disease. The median time of onset in patients initially immunosuppressed with cyclosporine-A (CsA)-containing regimens was 4.4 months after transplant, regardless of tumor clonality. A strong association of PTLD with Epstein-Barr virus (EBV) was observed. A histologic spectrum of lesions from polymorphic to monomorphic was observed. Whereas polymorphic lesions could be either clonal or nonclonal, monomorphic lesions appeared to be clonal in composition. The presence of large atypical cells (atypical immunoblasts) or necrosis did not appreciably worsen the prognosis. Twelve patients had clonal, 13 had nonclonal, and five had both clonal and nonclonal tumors. Clonality was indeterminate in 13 cases. Most patients were treated with a regimen based on reduced immunosuppression and supportive surgery. Almost all nonclonal and about half of the clonal lesions respond to this conservative therapy, indicating that it is an appropriate first line of treatment. This behavior suggests that a spectrum of lesions ranging from infectious mononucleosis to malignant lymphoma constitutes the entity known as PTLD. Some monoclonal tumors can undergo regression, however, apparently in response to host immune control mechanisms. Because of its short latency and strong association with EBV, PTLD is an important model for the study of virus-associated tumor progression in humans. 相似文献
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Prakash N. Rao PhDa f Xin Cai MDa f Raman Venkataramanan PhDb Jeffrey L. Platt MDd Anthony Demetris MDa c Allen Thunberg MDe Connie Faltynek PhDe Thomas Starzl MD PhDa Prem Kumar MDf 《The Journal of allergy and clinical immunology》1995,95(6)
Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506. Mean survival time was increased significantly in these animals (p < 0.007) to 40.6 ± 25.6 days as compared with either untreated rats (10.0 ± 2.7 days) or rats treated with 0.04 mg/kg FK-506 alone (13.7 ± 4.2 days). Histologic examination demonstrated a significant reduction in the cellular infiltrate in rats treated with PEG-SOD plus FK-506, as compared with recipients treated with either agent alone or left untreated. Our results therefore suggest a potential approach to reducing immunosuppression in transplantation. (J ALLERGY CLIN IMMUNOL 1995;95:1276-81.) 相似文献
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Metes D Logar A Rudert WA Zeevi A Woodward J Demetris AJ Abu-Elmagd K Eghtesad B Shapiro R Fung JJ Trucco M Starzl TE Murase N 《Human immunology》2003,64(8):787-795
Passenger leukocytes have been demonstrated to play significant roles in initiating and also regulating immune reactions after organ transplantation. Reliable techniques to detect donor leukocytes in recipients after organ transplantation are essential to analyze the role, function, and behavior of these leukocytes. In this report we describe a simple, reliable method to detect donor cells with low frequencies using peripheral blood samples. Detection of small numbers of major histocompatibility complex (MHC) mismatched cells was first studied using four-color flow cytometry in artificially created cell mixtures. By selecting the CD45(+) population and simultaneous staining with several leukocyte lineage markers (CD3, CD4, CD8, CD56, and CD19), MHC-mismatched leukocytes were consistently detected in cell suspensions prepared from directly stained whole blood samples with a threshold sensitivity as low as 0.1%-0.2%. When the fresh peripheral blood mononuclear cells were separated by conventional Ficoll gradient purification, similar, but slightly lower levels of donor cells were detected. Blood samples obtained 1-5 months after liver, kidney, and intestine transplants revealed that the kind of organ allograft influenced levels and lineage pattern of the circulating donor cells. This procedure provided a simple and reliable method in determining early chimerism in transplant recipients. However, the detection of MHC-mismatched leukocytes of all lineages was much lower when frozen peripheral blood mononuclear cells were used. 相似文献
5.
Liver transplantation (2) 总被引:7,自引:0,他引:7
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Pathology of hepatic transplantation: A review of 62 adult allograft recipients immunosuppressed with a cyclosporine/steroid regimen. 总被引:8,自引:2,他引:8
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A. J. Demetris S. Lasky D. H. Van Thiel T. E. Starzl A. Dekker 《The American journal of pathology》1985,118(1):151-161
The pathologic specimens (n = 118) and hospital course pertinent to each of 62 adult liver allograft recipients were reviewed. Biopsies and retransplanted organs were obtained at the discretion of the surgical team on the basis of the postoperative clinical course (less than 1 day to greater than 12 years after transplantation), and final interpretation of the pathologic material was based on a correlation of all available data. Most of the specimens (n = 85) were obtained within the first 2 months, and diagnoses in this time period included rejection, biliary obstruction/cholangitis, vascular injury, herpesvirus and cytomegalovirus hepatitis, graft necrosis, and functional cholestasis. Thereafter, rejection and recurrent or primary viral hepatitis were the major causes of graft dysfunction. Histologically, hepatic rejection is manifested by a cellular mediated injury of hepatocytes and bile ductules and a spectrum of vascular lesions in medium-sized hilar arteries. Morphologic changes of biliary duct obstruction and viral liver disease were at times difficult to differentiate from rejection. Two pretransplant disorders, type B viral hepatitis and the Budd-Chiari syndrome, recurred in grafted organs. Although interpretation of pathologic material may be difficult at times, it frequently is helpful in planning an approach to management of liver allograft recipients. 相似文献
7.
Immunomodulation for intestinal transplantation by allograft irradiation, adjunct donor bone marrow infusion, or both 总被引:8,自引:0,他引:8
Murase N Ye Q Nalesnik MA Demetris AJ Abu-Elmagd K Reyes J Ichikawa N Okuda T Fung JJ Starzl TE 《Transplantation》2000,70(11):1632-1641
BACKGROUND: The passenger leukocytes in the intestine have a lineage profile that predisposes to graft-versus-host disease (GVHD) in some animal models and have inferior tolerogenic qualities compared with the leukocytes in the liver, other solid organs, and bone marrow. Elimination by ex vivo irradiation of mature lymphoid elements from the bowel allografts is known to eliminate the GVHD risk. We hypothesized that infusion of donor bone marrow cells (BMC) in recipients of irradiated intestine would improve tolerogenesis without increasing the risk of GVHD. METHODS: Orthotopic small intestine transplantation was performed with the GVHD-prone Lewis (LEW)-to-Brown Norway (BN) combination and the reverse GVHD-resistant BN-to-LEW model under a short course of tacrolimus treatment (1 mg/kg/day, days 0-13, 20, 27). Grafts were irradiated ex vivo, using a 137Cs source. In selected experimental groups, donor BMC (2.5 x 10(8)) were infused on the day of small intestine transplantation. RESULTS: The unmodified LEW intestine remained intact, whether transplanted alone or with adjunct donor BMC infusion, but all of the BN recipients died of GVHD after approximately 2 months. Intestinal graft irradiation (10 Gy) effectively prevented the GVHD and prolonged survival to 92.5 days, but all of the BN recipients died with chronic rejection of the LEW grafts, which was prevented by infusion of adjunct donor BMC without causing GVHD. In the GVHD-resistant reverse strain direction (BN-->LEW), all intestinal recipients treated for 27 days with tacrolimus survived > or =150 days without regard for graft irradiation or adjunct BMC, but chronic rejection was severe in the irradiated intestine, moderate in the unaltered graft, and least in the irradiated intestine transplanted with adjunct BMC. Mild arteritis in the 150 day allografts of both strain combinations (i.e., LEW--> BN and BN-->LEW) may have been irradiation associated, but this was prevented when weekly doses of tacrolimus were continued for the duration of the experiment rather than being stopped at 27 days. CONCLUSIONS: Recipients are protected from GVHD by irradiating intestinal allografts, but the resulting leukocyte depletion leads to chronic rejection of the transplanted bowel. The chronic rejection is prevented with adjunct donor BMC without causing GVHD. Although application of the strategy may be limited by the possibility of radiation injury, the results are consistent with the paradigm that we have proposed to explain organ-induced graft acceptance, tolerance, and chronic rejection. 相似文献
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Stavros Gkolfinopoulos Panteleimon Kountourakis Demetris Papamichael 《Current colorectal cancer reports》2016,12(1):9-17
Colorectal cancer is a disease affecting mainly older people, a fact that is becoming more apparent with the global population aging. However, this patient group is more likely to be subjected to suboptimal treatment due to a number of factors, but most commonly as a result of the physician’s weakness to recognize those fit for the full spectrum of cancer therapy. In this regard, clinical screening tests, such as the Comprehensive Geriatric Assessment, can be invaluable in guiding treatment decisions. Fluoropyrimidine-based adjuvant chemotherapy clearly confers a survival advantage in older individuals with node-positive disease; however, the benefit from the administration of oxaliplatin-based regimens is less clear. Palliative chemotherapy also has an important role in managing metastatic disease, and with the use of novel targeted agents it can potentially prolong survival and improve quality of life. The management of rectal cancer in this population can present a challenge, since it appears that the optimal treatment of chemoradiation followed by total mesorectal excision can be applied in select few. Indeed, the morbidity and mortality rates in older people treated with these combined modalities can be too high, guiding many physicians to opt for more conservative approaches, directed at providing palliation and local control, especially in those with limited life expectancy. In conclusion, in order to provide the best care in an older colorectal cancer patient, we need to individualize our approach, selecting the right patient for the right treatment. 相似文献