ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results.Methods.Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes.Results.The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium.Conclusions.Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Nuclear factor-&kgr;B (NF-&kgr;B) is a transcription factor that upregulates adhesion molecules ICAM-1, VCAM-1, and ELAM-1. We hypothesized the use ofex vivopressure-mediated delivery of transcription factor decoys (TFD) to NF-&kgr;B binding sites would decrease expression of adhesion molecules, and decrease reperfusion injury, acute rejection, and graft coronary artery disease (GCAD) in rat cardiac allografts.Methods.Heterotopic heart transplants were performed on donor hearts treated with saline, 10 mg/kg LPS, 160 &mgr;mol/L NF-&kgr;B TFD, or 160 &mgr;mol/L scrambled sequence (NF-SC) TFD for 45 min at 78 psi (6 atm). Transfection efficiency was determined with FITC-labeled TFD. Reverse transcription-PCR and immunohistochemistry was used to analyze adhesion molecule mRNA and protein e-pression, respectively. Apoptosis was measured with DNA fragmentation analysis. Reperfusion injury was assessed with cardiac edema, neutrophil infiltration, and histology. Acute rejection was determined by daily palpation. Allografts were assessed at POD 90 for the development of GCAD by computer-assisted image analysis to determine intimal:medial ratio and myointimal proliferation.Results.Hyperbaric pressure was an effective method of NF-&kgr;B TFD delivery (P<0.001 vs. controls). NF-&kgr;B TFD treatment led to decreased mRNA and protein expression of adhesion molecules. Treatment with NF-&kgr;B TFD led to a significant decrease in all reperfusion injury parameters compared to saline and NF-SC controls (P<0.01 vs. controls). Higher levels of apoptosis were seen in allografts treated with NF-&kgr;B TFD compared to control allografts. NF-&kgr;B TFD treatment prolonged allograft survival over saline and NF-SC controls (P<0.05). Myointimal proliferation and intimal:medial ratios in NF-&kgr;B TFD-treated allografts were significantly decreased compared to saline and NF-SC treatment (P<0.00001).Conclusions.Ex vivopressure-mediated delivery of NF-&kgr;B TFD is an effective method to block adhesion molcule expression and reperfusion injury in the immediate posttransplant period. Further, NF-&kgr;B TFD treatment prolongs allograft survival and decreases GCAD.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Ischemia-reperfusion injury (IRI) is often responsible for graft rejection and leads to delayed graft function of cadaveric kidneys. We have shown that adding polyethylene glycol (PEG 20M) to the preservation solutions helps protect isolated perfused pig kidneys against cold ischemia and reperfusion injury.Methods.We compared the effects of adding PEG to a simplified high-K+perfusion solution of cold-stored kidneys to Euro-Collins or University of Wisconsin solutions on the function of reperfused autotransplanted pig kidneys. The left kidney was cold-flushed with the preservation solutions and stored for 48 hr at 4°C before reimplantation. Creatinine clearance and fractional excretion of sodium were analyzed 2 days before surgery and over 7 days after transplantation. Histological sections were obtained 40 min after reperfusion and on day 7 after surgery.Results.Adding PEG to the perfusate significantly reduced IRI from autotransplanted pig kidneys. Creatinine clearance was significantly higher and fractional excretion of sodium was significantly lower in pigs transplanted with kidneys cold-flushed with PEG-supplemented perfusate than in those flushed with Euro-Collins or University of Wisconsin solutions. PEG supplementation also better preserved the integrity of kidney cells and markedly reduced interstitial cell infiltrates.Conclusion.PEG protects against IRI and reduces early cellular inflammation. PEG may impair the recruitment and migration of leukocytes into retransplanted pig kidneys. Cold preservation of donor organs with PEG-supplemented solutions may therefore help limit IRI in human renal transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The present study was undertaken in order to: (a) develop a new technique for measurement of interstitial pressure, (b) study the intragraft pressure of rejecting and non-rejecting organs, and (c) study the effect of treatment with the hyaluronan-degrading enzyme hyaluronidase on intragraft pressure. Treatment with hyaluronidase has previously been demonstrated to result not only in reduction of tissue hyaluronan but also in ameliorated interstitial edema, and we suggested that the diminished edema would lead to a reduced interstitial pressure as well.Methods.At day 5 after syngeneic or allogeneic rat heterotopic heart transplantation, the interstitial pressure of the cardiac grafts was measured using a microtip pressure sensor. Subsequently, the allogeneically grafted animals received a continuous intravenous infusion of either hyaluronidase (total dose: 60,000 U/kg) or vehicle during 2 hr; meanwhile, the interstitial pressure was monitored.Results.The intragraft pressure measurement technique was found to give reproducible results. The interstitial pressure of the rejecting (allogeneic) grafts was considerably higher than that of the non-rejecting (syngeneic), i.e., 12.3±1.6 mmHg vs. 1.1±0.6 mmHg (P<0.001). Hyaluronidase infusion effectively reduced the interstitial pressure as compared with vehicle treatment. By 20 min, the pressure had been reduced by 28% (P<0.01 compared with vehicle treatment); after 1 hr, by 49% (P<0.001); and after 2 hr, by 68% (P<0.01).Conclusions.By using modern technology for tissue pressure measurements, we found that the strongly increased interstitial pressure of rejecting organs can be instantly reduced by intravenous administration of the hyaluronan-degrading enzyme hyaluronidase.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities, to assess the clinical significance, and to identify predictive factors for these pathological changes.Methods.The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors for the histological abnormalities in the biopsies was performed by a multivariate logistic regression analysis.Results.The incidence of portal fibrosis (PF) was 31%. Liver function tests showed except for the albumin level, an increase in the PF group compared with the group without PF. Mean values of alkaline phosphatase and direct bilirubin were 264 U/liter and 3 &mgr;mol/liter, respectively, in the normal group, and 435 U/liter and 23 &mgr;mol/liter, respectively, in the PF group (P=0.043 and 0.037). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time, preservation solution, type of allograft, cytomegalovirus recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for cold ischemia time, biliary complications, and cytomegalovirus status. Acute rejection showed a negative correlation.Conclusions.The incidence of PF within 1 year post liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged cold ischemia time, biliary complications, and a positive cytomegalovirus recipient status. Acute rejection seemed to prevent for PF.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Extensive third degree burn wounds can be permanently covered by the transplantation of autologous cultured keratinocytes.Many modifications to Green and colleagues’ original technique have been suggested, including the use of a fibrin matrix. However, the properties of the cultured cells must be assessed using suitable criteria before a modified method of culture for therapeutic purposes is transferred to clinical use, because changes in culture conditions may reduce keratinocyte lifespan and result in the loss of the transplanted epithelium.Methods.To evaluate the performances of human keratinocytes grown on a fibrin matrix, we assay for their colony-forming ability, their growth potential and their ability to generate an epidermis when grafted onto athymic mice. The results of these experiments allowed us to compare side by side the performance for third degree burn treatment of autologous cultured epithelium grafts grown according to Rheinwald and Green on fibrin matrices with that of grafts grown directly on plastic surfaces.Results.We found that human keratinocytes cultured on a fibrin matrix had the same growth capacity and transplantability as those cultured on plastic surfaces and that the presence of a fibrin matrix greatly facilitated the preparation, handling, and surgical transplantation of the grafts, which did not need to be detached enzymatically. The rate of take of grafts grown on fibrin matrices was high, and was similar to that of conventionally cultured grafts. The grafted autologous cells are capable of generating a normal epidermis for many years and favor the regeneration of a superficial dermis.Conclusion.We have demonstrated that: 1) fibrin matrices have considerable advantages over plastic for the culture of skin cells for grafting and that it is now possible to generate and transplant enough cultured epithelium from a small skin biopsy to restore completely the epidermis of an adult human in 16 days; and 2) the generated epidermis self-renews itself for years. The use of fibrin matrices thus significantly improves the transplantation of cultured epithelium grafts for extensive burns as recently demonstrated in a follow-up work.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Lung transplantation is increasingly used as the treatment for many end-stage pulmonary diseases. A major cause of morbidity and mortality in patients who undergo lung transplantation is rejection of the allograft. Proinflammatory macrophage-derived cytokines may sustain and/or enhance the immunological response to lung allograft antigens. Nuclear factor-&kgr; B (NF-&kgr;B) is a transcription factor that regulates the production of many of these cytokines and growth factors in alveolar macrophages (AMs). The aim of our study was to evaluate the activation of NF-&kgr;B in AMs and the levels of one of the proinflammatory cytokines whose production it controls, macrophage inhibitory protein-1&agr; (MIP-1&agr;), in AMs from transplanted lungs compared to those from healthy controls.Methods.Twenty-eight (28) transplant recipients were included in the study. NF&kgr;B activation was evaluated by electrophoretic mobility shift assay of whole cell extracts and by immunohistochemical analysis on cytospin preparations. Concentrated bronchoalveolar lavage fluid was analyzed by enzyme-linked immunosorbent assay for MIP-1&agr; levels.Results.NF-&kgr;B was activated in alveolar macrophages from transplant patients as compared to healthy controls. MIP-1&agr; levels in epithelial-lining fluid were elevated in transplant patients as compared to healthy controls. Increased MIP-1&agr; levels correlated with viral infections in the transplant patients. Neither finding was found to correlate with acute rejection by transbronchial biopsy.Conclusions.These results demonstrate that NF-&kgr;B activation and MIP-1&agr; levels are increased in transplanted lungs and may play a role in the inflammatory cytokine cascade that leads to the long-term tissue damage and allograft rejection in these patients.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID