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1. |
CYTOKINE CASCADES IN ACUTE GRAFT-VERSUS-HOST DISEASE1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 553-558
Krenger2 Werner,
Hill Geoffrey,
Ferrara3 James,
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ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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2. |
PREGNANCY AFTER LIVER TRANSPLANTATION UNDER TACROLIMUS1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 559-565
Jain2 Ashok,
Venkataramanan3 Raman,
Fung2 John,
Gartner4 J.,
Lever5 Jackie,
Balan2 Vijayan,
Warty2 Vijay,
Starzl2,6 Thomas,
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摘要:
Background.The maternal and fetal risk of pregnancy after organ transplantation under tacrolimus has not been reported. This was prospectively studied in 27 pregnancies by 21 female liver recipients who were treated with tacrolimus before and throughout gestation.Method.Twenty-seven babies were born between October 1990 and April 1996. In 15 cases, samples were obtained at or after delivery and stored (-40°C) for comparison of tacrolimus concentration in the maternal blood with different combinations of cord and infant venous blood, breast milk, or a section of the placenta.Results.The 21 mothers had surprisingly few serious complications of pregnancy and no mortality. Two infants with 23 and 24 weeks gestation died shortly after birth. The mean birth weight of the other 25 was 2638±781 g after a gestational period of 36.6±3.3 weeks. Mean birth weight percentile for gestational age was 50.2±26.2 (median 40). On the day of delivery, the mean tacrolimus concentrations (ng/ml) were 4.3 in placenta versus 1.5, 0.7, and 0.5 in maternal, cord, and child plasma, and 0.6 in the first breast milk specimens. The infants had a 36% incidence of transient perinatal hyperkalemia (K+>7.0 meq/L) and a mild reversible renal impairment, which were thought to reflect in part maternal homeostasis. One newborn had unilateral polycystic renal disease (the only anomaly). All 25 babies have had satisfactory postnatal growth and development with a current mean weight percentile of 62±37 (median 80).Conclusions.Pregnancy by postliver transplant mothers under tacrolimus was possible with a surprisingly low incidence of the hypertension, preeclampsia, and other maternal complications historically associated with such gestations. As in previous experience with other immunosuppressive regimens, preterm deliveries were common. However, prenatal growth for gestational age and postnatal infant growth for postpartum age were normal.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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3. |
FAT ABSORPTION AFTER SMALL INTESTINAL TRANSPLANTATION IN THE RAT1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 566-571
Winkelaar2 Gerrit,
Smith3 Leslie,
Martin4 Gary,
Sigalet4,5 David,
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摘要:
Background.Intestinal transplantation is now used for patients with severe malabsorption, however, little data exists quantifying the ability of the graft to absorb fat. This study tested the hypothesis that intestinal transplantation would not affect the lymphatic or venous uptake of fatty acids.Methods.A syngeneic rat model of intestinal transplantation (SIT) with caval drainage of the graft was used. Control animals underwent intestinal division and reanastomosis (n=15 in each group). The animals were followed for 6 weeks, and fat absorption in vivo was quantified. The animals were anesthetized, sampling catheters were placed in the jugular and superior mesenteric veins and in the mesenteric lymphatic duct, and a feeding tube was passed into the duodenum. Animals were allowed to recover, and a steady-state duodenal infusion of lauric (C12:0) and palmitic (C16:0) fatty acid emulsion was begun. A radiolabeled pulse of lauric (C12:0) and palmitic (C16:0) fatty acid was then given, and the subsequent appearance in the lymphatic and venous systems was quantified.Results.In vivo absorption of dietary fat was preserved, but after transplantation the mesenteric lymphatic flow and cumulative lymphatic appearance of both labels was significantly reduced (flow reduced from 4.8±1.1 in controls to 1.0±0.29 ml/hr in transplant animals, whereas lauric acid absorption was 33±11.4% in controls vs. 7.5±2.5% in transplant animals). There was a modest increase in the jugular venous appearance of the fatty acids (2.0±1.1% in transplant animals vs. 0.75±0.55% in controls for lauric acid;P<0.05 for all comparisons). Absorption of lauric and palmitic acids was very similar, and there was no preferential absorption detected in the portal venous system. Dye studies demonstrated lymphatic recannulization around the vascular anastomosis, into the retroperitoneum.Conclusions.These results suggest that in this model of SIT, fat absorption via the mesenteric duct is reduced, but that compensatory collaterals form into the retroperitoneal lymphatics. There was no evidence of any significant increase in portal venous uptake of fatty acids after SIT, nor of preferential absorption of medium-chain fatty acids. These results may have implications for patients after SIT.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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4. |
CD4+AND CD8+T CELLS EACH CAN UTILIZE A PERFORIN-DEPENDENT PATHWAY TO MEDIATE LETHAL GRAFT-VERSUS-HOST DISEASE IN MAJOR HISTOCOMPATIBILITY COMPLEX-DISPARATE RECIPIENTS1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 571-576
Blazar2,3 Bruce,
Taylor3 Patricia,
Vallera4 Daniel,
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摘要:
Perforin-deficient (-/-) mice were used as T-cell donors for infusion into irradiated major histocompatibility complex (MHC)-disparate recipients to investigate the requirement for perforin-mediated cytolysis during graft-versus-host disease (GVHD) generation. Administration of 5×106C57BL/6 (H2b) perforin -/- splenocytes was significantly less effective in inducing GVHD lethality when given to MHC class I + II disparate B10.BR (H2k) recipients, as compared with wild-type (+/+) controls. Perforin expression by donor T cells was not required for GVHD induction because recipients given fivefold higher numbers of perforin -/- donor splenocytes uniformly succumbed to lethal GVHD. Because both CD4+and CD8+donor T cells are required for optimal GVHD lethality in this strain combination, to discern the relative contribution of perforin-mediated cytolysis by CD4+and CD8+T cells, additional studies were performed. For these latter studies, we used a sensitive assay involving the infusion of highly purified CD4+or CD8+T cells into sublethally irradiated MHC class II or I disparate recipients, respectively. As compared with recipients of perforin +/+ T cells, recipients of either CD4+or CD8+perforin -/- T-cell subsets had a significant reduction in GVHD-mediated lethality at T-cell doses that were uniformly lethal. T-cell dose titration studies established that GVHD lethality in recipients of perforin -/- CD4+or CD8+T cells was reduced by approximately threefold. These data are the first to indicate that approaches to limit perforin-mediated cytolysis should be similarly effective in situations in which CD4+or CD8+T cells dominate the GVHD response.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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5. |
EFFECT OF PROLONGED HYPOTHERMIC ISCHEMIA AND REPERFUSION ON OXYGEN CONSUMPTION AND TOTAL MECHANICAL ENERGY IN RAT MYOCARDIUMParticipation of Mitochondrial Oxidative Phosphorylation1,2,† |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 577-583
Kuwabara3 Masachika,
Takenaka4,5 Hitoshi,
Maruyama4 Hideharu,
Onitsuka3 Toshio,
Hamada4,6 Minoru,
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摘要:
Background.To reduce ischemia-reperfusion injury of hearts in open heart surgery and transplantation, it is important to know the critical period of ischemia in which donor hearts can sustain their function satisfactorily. Cardiac function has been deduced from oxygen consumption (VO2) and mechanical parameters such as pressure-volume area (PVA). Inhibited mitochondrial oxidative phosphorylation during ischemia indicates that ATP production is uncoupled from VO2. Therefore, both mitochondrial oxidative phosphorylation and total mechanical energy should be examined to evaluate cardiac function after ischemia and reperfusion.Methods.Isolated rat hearts were stored in Euro-Collins solution at 4°C for 8, 12, and 24 hr and reperfused in a working mode with a modified Krebs-Henseleit bicarbonate solution. PVA and VO2were examined in isovolumic contraction, and ventricular contractility and total mechanical energy were assessed, respectively, by the end-systolic elastance (Ees) and PVA. Mitochondrial oxidative phosphorylation in the presence of succinate and mitochondrial lipid peroxide levels were estimated in similarly treated rat hearts.Results.Ees was decreased by ischemia without significant difference. The VO2to PVA ratio remained linear, although VO2at null PVA and the VO2to PVA ratio significantly increased after 12 hr of ischemia. Mitochondrial oxidative phosphorylation was decreased significantly by reperfusion after 12 hr of ischemia. Mitochondrial lipid peroxide levels were increased significantly after 12 hr of ischemia.Conclusions.In isolated rat hearts, decreased efficiency for energy conversion from consumed oxygen to cardiac performance occurs between 8 and 12 hr of hypothermic ischemia, which was coincident with disturbed mitochondrial oxidative phosphorylation, to which lipid peroxidation may contribute.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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6. |
ISLET ALLO- AND XENOTRANSPLANTATION IN NORMAL, INTERCELLULAR ADHESION MOLECULE-1-DEFICIENT, AND P SELECTIN-DEFICIENT MICE1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 584-589
Sandberg2,3,4 Jan-Olov,
Korsgren2 Olle,
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摘要:
Background.Recently, inhibition of transplant rejection by pretreatment of xenogeneic pancreatic islets cells with antibodies to intercellular adhesion molecule (ICAM)-1 was reported. These promising results together with the development of mice deficient in P selectin or ICAM-1 encouraged further evaluation of the role of these two molecules in allo- and xenogeneic pancreatic islet transplantation. These deficient mice provide powerful tools to study the complex role of cell adhesion molecules in the cellular interactions between graft and recipient that culminate in graft rejection.Methods.ICAM-1-deficient mice served as both donors and recipients, but P selectin-deficient mice served only as recipients, in allogeneic and concordant xenogeneic (mouse-to-rat) transplantations. Both ICAM-1- and P selectin-deficient mice served as recipients in discordant xenogeneic (pig to mouse) transplantations. Two hundred collagenase-isolated pancreatic islets or fetal porcine islet-like cell clusters were transplanted under the renal capsule of the recipients. Animals were killed 7 days after transplantation, and the rejection process was evaluated with immunohistochemical techniques.Results.The use of ICAM-1- or P selectin-deficient mice did not influence the infiltration of T cells, macrophages, or natural killer cells in the islet grafts. Nor did preincubation of islet-like cell clusters with ICAM-1 monoclonal antibody inhibit the xenogeneic rejection process. In allograft rejection, an equivalent number of T cells and macrophages were present. Among the T cells, the CD8-positive subtype dominated. Quite in contrast, macrophages were the dominating infiltrating cell type in the discordant xenografts. The pattern of cellular infiltration in the concordant xenografts was more complex and seemed to share components from both allo- and xenograft rejection.Conclusions.Thus, disturbance of the expression of ICAM-1 or P selectin in either the recipient or in the islet-graft did not influence allo- or xenograft rejection.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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7. |
SKIN ALLOGRAFT REJECTION IN MICE LACKING INDUCIBLE NITRIC OXIDE SYNTHASE1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 589-593
Casey2 John,
Wei3 Xiao-Qing,
Orr2 Douglas,
Gracie2 J.,
Huang3 Fang-Ping,
Bolton2 Eleanor,
Liew3 Foo,
Bradley2,4 J.,
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摘要:
Background.During allograft rejection, up-regulation of cytokine-inducible nitric oxide synthase (iNOS) leads to the production of large amounts of nitric oxide (NO). The net effect of NO on the alloimmune response is, however, difficult to predict because of its diverse biological effects, which include potentially opposing roles as an effector and immunoregulatory molecule.Methods.In this study, the role of iNOS on the in vitro and in vivo alloimmune response was defined using mutant mice that lack a functional iNOS gene. The ability of spleen cells obtained from iNOS-deficient mutants to proliferate and to produce cytokines in response to irradiated BALB/c stimulator cells was determined, and the rate at which iNOS-deficient mice were able to reject BALB/c skin allografts was observed.Results.Spleen cells from homozygous iNOS-deficient (129×MF1)F1mice, when compared with cells from heterozygous control mice, showed an increased in vitro proliferative response and produced substantially higher levels of interferon-γ, and also more interleukin-2 and interleukin-12, in response to allogeneic stimulation. The kinetics of BALB/c skin graft rejection were comparable in heterozygous control animals and iNOS-deficient mice. Moreover, no net effect of iNOS on skin allograft rejection was apparent in mice treated with depleting monoclonal antibodies (mAb) to CD4 or CD8 T cells, either alone or in combination, or in mice treated with both anti-CD8 mAb and a neutralizing anti-tumor necrosis factor mAb.Conclusions.These results show that iNOS has an immunomodulatory effect on the in vitro alloimmune response but lack of iNOS has no net influence on the kinetics of murine skin allograft rejection in either unmodified recipients or recipients in which the early contribution of T-cell subsets and tumor necrosis factor-α to graft rejection has been abrogated.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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8. |
TACROLIMUS (FK506) DOWN-REGULATES FREE RADICAL TISSUE LEVELS, SERUM CYTOKINES, AND NEUTROPHIL INFILTRATION AFTER SEVERE LIVER ISCHEMIA |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 594-598
Garcia-Criado1 F.,
Palma-Vargas2 J.,
Valdunciel-Garcia1 J.,
Toledo2 A.,
Misawa2 K.,
Gomez-Alonso1 A.,
Toledo-Pereyra2,3,4 L.,
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摘要:
Background.Liver ischemia and reperfusion injury is associated with activation of multiple inflammatory pathways, including free radicals, cytokines, and neutrophil-mediated tissue damage among others. Tacrolimus (FK506) has shown important regulatory effects on some inflammatory pathways, such as cytokines, neutrophils, and adhesion molecules. In this study, we explored a new potential protective mechanism for tacrolimus in the liver inflammatory response after ischemia and reperfusion, specifically its effect on liver tissue free radicals.Methods.Total hepatic ischemia was produced in the rat for 90 min with an extracorporeal portosystemic shunt. Animals (n=96) were divided into four groups: group 1 comprised normal rats for reference values; group 2 comprised sham operated rats; in group 3, ischemic control rats received only the vehicle; and the experimental treatment group, group 4, received tacrolimus at a dose of 0.3 mg/kg, 4 hr before ischemia. Animal survival was followed up to 7 days. Liver function tests were performed and liver tissue free radicals and myeloperoxidase, serum cytokines (interleukin 1, tumor necrosis factor-α), and liver histology were measured 4 hr after reperfusion.Results.Seven-day survival was significantly improved from only 20% in the control group to 55% in the tacrolimus group (P<0.01). Liver function tests, histology, and myeloperoxidase tissue values were significantly improved (P<0.05) with tacrolimus pretreatment. Furthermore, a significant (P<0.05) down-regulation of serum cytokines and liver tissue free radicals was observed.Conclusions.These data indicate a new and different protective mechanism for FK506 in regard to its ability to down-regulate free radical levels in livers subjected to severe ischemia and reperfusion. Tacrolimus, also confirmed to be a potent suppressor of the cytokine response, specifically interleukin 1 and tumor necrosis, decreased neutrophil tissue migration as well.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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9. |
SHOULD OBESE PATIENTS LOSE WEIGHT BEFORE RECEIVING A KIDNEY TRANSPLANT? |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 599-604
Modlin Charles,
Flechner1 Stuart,
Goormastic Marlene,
Goldfarb David,
Papajcik Doreen,
Mastroianni Barbara,
Novick Andrew,
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摘要:
Background.The results of renal transplantation in obese recipients have been controversial, with some reports finding increased morbidity prohibitive and others finding increased morbidity acceptable. We attempted to determine whether obese patients in extreme excess of their ideal body weight should undergo transplantation.Methods.The study population included 127 obese (body mass index >30 kg/m2) patients who were compared with a matched nonobese control group (body mass index <27 kg/m2) of 127 recipients with similar demographics. There were no significant differences between the groups according to donor source, recipient race or sex, retransplants, transplant percent reactive antibodies, cause of renal failure, or hypertension. However, significantly more obese patients had a pretransplant history of angina (11.2% vs. 3.2%,P=0.02) or a previous myocardial infarction (5.6% vs. 0.8%,P=0.04).Results.The mean follow-up was 58.9±40 (range 3-170) months. Nonobese patients enjoyed a significantly (P=0.0002) greater patient survival (89% vs. 67%) at 5 years and suffered only about half the number of deaths (25 vs. 46) during the period of observation. Cardiac disease was the leading cause of death (39.1%) in the obese group. Patient death had a major impact on graft survival because there were no differences between the groups when death with graft function was censored from the analysis. There were no significant differences between the groups in delayed graft function, acute rejection, chronic rejection, length of hospital stay, operative blood loss, or mean serum creatinine up to 5 years. However, obese patients experienced significantly (P=0.0001) more complications per patient (3.3 vs. 2.2) and a greater incidence (P=0.0003) of posttransplant diabetes (12% vs. 2%). Similar cyclosporine blood levels were observed in obese recipients even though they were receiving 0.75-2 mg/kg/day less cyclosporine than the nonobese recipients.Conclusions.Outcome differences in obese renal transplant patients were primarily due to a higher mortality resulting from cardiac events. Obesity seems to have little effect on immunologic events, long-term graft function, or cyclosporine delivery. Aggressive pretransplant screening for ischemic heart disease is essential to identify an especially high-risk subgroup of obese patients. Although it would seem prudent to recommend weight reduction <30 kg/m2to all patients before transplant, these data suggest that obese patients with a history of cardiac disease should not be transplanted until weight reduction has been accomplished.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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10. |
THE FACTOR V LEIDEN (R506Q) MUTATION AND RISK OF THROMBOSIS IN RENAL TRANSPLANT RECIPIENTS1 |
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Transplantation,
Volume 64,
Issue 4,
1997,
Page 604-607
Irish2 Ashley,
Green3,4 Fiona,
Gray2 Derek,
Morris2 Peter,
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摘要:
Background.Renal transplantation and chronic renal failure are associated with an increased risk of venous thrombosis and myocardial infarction (MI). We investigated whether resistance to activated protein C due to a mutation in the factor V gene (FV Leiden/FV506Q) may predispose patients to thrombosis.Methods.Three hundred patients who had undergone renal transplantation were genotyped for the FV mutation. Seventy-seven patients who had suffered thrombotic complications (42 venous, 28 arterial, and 7 both) were compared with 223 patients free of thrombosis.Results.Thirty-two patients had suffered early renal allograft thrombosis (30 venous), and 33 patients had suffered MI. A higher proportion of the patients with thrombosis, compared to those without, had a family history of arterial cardiovascular disease (42% vs. 26%,P=0.04). Eighteen (6%) patients were heterozygous for FV506Q and seven (39%) of these had suffered venous thrombosis (including four primary allograft thromboses), compared with 15% of the patients without the mutation (P<0.05). The odds ratio for risk of venous thrombosis for FV506Q carriers was 3.6 (95% confidence interval: 1.3-9.9) or 4.0 (1.2-13.8) for primary allograft thrombosis. Only one of the FV506Q carriers had suffered an MI.Conclusions.Carriers of the factor V 506Q mutation with chronic renal failure who have undergone transplantation are at an increased risk of venous but not arterial thrombosis. This mutation explained 14% of all venous and 20% of primary allograft thrombosis, suggesting that other unidentified genetic and environmental factors contribute to the risk of thrombosis in renal transplant recipients.
ISSN:0041-1337
出版商:OVID
年代:1997
数据来源: OVID
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