ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Studies in vivo have documented the importance of CD40-gp39 interactions in the development of T-dependent antibody responses to foreign and auto-antigens. In this report, we demonstrate that allograft rejection is also associated with strong induction of CD40 and gp39 transcripts. When treatment was initiated at the time of transplant, MR1, a mAb specific for gp39, induced markedly prolonged survival of fully disparate murine cardiac allografts in both naive and sensitized hosts. However, when therapy was delayed until postoperative day 5, anti-gp39 failed to prolong graft survival. Allografts from recipients treated with MR1 from the time of transplantation showed decreased expression of transcripts for the macrophage effector molecule, inducible nitric oxide synthase, but essentially unaltered expression of B7 molecules and T cell cytokine transcripts (interleukin[IL]-2, interferon-γ, IL-10, and IL-4) relative to control allografts. In addition, alloantibody responses in the MR1-treated mice were profoundly inhibited. However, our studies using B cell-deficient mice indicated that the ability of MR1 to prolong allograft survival was not dependent on B cells. These data suggest that blockade of CD40-gp39 interactions may inhibit allograft rejection primarily by interfering with T cell help for effector functions, rather than by interference with T cell activation.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Indefinite survival of concordant xenogeneic Wistar Furth (WF) rat islet survival was obtained by intrahepatic transplants of cultured WF islets and a single injection of antilymphocyte sera in C57BL/6 mice. Adoptive transfer of splenocytes from mice with established WF islet xenografts produced a marked prolongation of survival of WF islets transplanted under the kidney capsule of diabetic irradiated (600 rads), naive C57BL/6 recipients(mean survival time = 48.9±17.1 days), and three of the recipients were still normoglycemic at 100 days after transplantation. Adoptive transfer of an equal mixture (3×107cells each) of these splenocytes with normal splenocytes also prolonged survival of the kidney capsule islet xenografts(mean survival time = 26.5±7.8 days vs. 15.2±5.3 days for controls). In vitro studies on lymphocyte proliferation demonstrated a low rate of proliferation of splenocytes from established islet xenografts in the presence of irradiated WF splenocytes (stimulation index = 1.6 vs. 16.2 for naive C57BL/6 mice), and mixing the cells with control splenocytes also decreased the proliferation of splenocytes as compared with controls(stimulation index = 5.4 vs. 16.2 in controls). The inhibitory effect was not species specific, since splenocytes from mice with established islet xenografts also produced a 42% inhibition of proliferation in the presence of irradiated Lewis splenocytes. These findings demonstrate that concordant, islet xenograft, immune unresponsiveness can be adoptively transferred by splencotyes from mice with established islet xenografts.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Organ xenografts in discordant combinations such as pig-to-man undergo hyperacute rejection due to the presence of naturally occurring human anti-pig xenoantibodies. The galactose α(1,3)-galactose epitope on glycolipids and glycoproteins is the major porcine xenoantigen recognized by these xenoantibodies. This epitope is formed byα(1,3)-galactosyltransferase, which is present in all mammals except man, apes, and Old World monkeys. We have generated mice lacking this major xenoantigen by inactivating the α(1,3)-galactosyltransferase gene. These mice are viable and have normal organs but develop cataracts. Substantially less xenoantibody from human serum binds to cells and tissues of these mice compared with normal mice. Similarly, there is less activation of human complement on cells from mice lacking the galactose α(1,3)-galactose epitope. These mice confirm the importance of the galactoseα(1,3)-galactose epitope in human xenoreactivity and the logic of continuing efforts to generate pigs that lack this epitope as a source of donor organs.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The depletion of biochemical energy stores during anoxic ischemic preservation is a major problem affecting the viability of the graft in transplantation medicine. After cessation of blood flow and, thus, lack of metabolic substrates and oxygen supply, a swift decrease of energy-rich phosphates can be observed in the tissue, since endergonic metabolic processes continue, but no further oxidative regeneration of biochemical energy stores will take place.We investigated the effect of a continuous gaseous oxygen supply via the venous vessels during extended ischemic preservation of rat livers in University of Wisconsin preservation solution for 48 hr. Results showed that aerobic ischemic storage not only prevented the depletion of biochemical energy stores, but promoted a de novo synthesis of high energy phosphates, and significantly enhanced the functional recovery of the organs after postischemic reperfusion.The findings suggest that maintenance of oxidative energy metabolism largely protects the organ during ischemia and may enable organ viability even after extended preservation times.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The effect of changing pulmonary artery pressure during flushing(flushing pressure) on lung preservation was examined in an ex vivo rabbit lung perfusion model. Both lungs were flushed in situ with 200 ml of a preservation solution (extracellular fluid [ECF] type) at 8°C, at a constant flushing pressure maintained by regulating the flushing flow rate from 20 to 120 ml/min. In the controls, the flushing pressure was maintained at 15 mmHg and the lungs were assessed without storage. In the other 5 groups(n=7 in each group), the lungs were flushed at pressures of 5, 10, 15, 20, and 25 mmHg, respectively. The heart-lung block was then harvested, and immersed in the same solution at 8°C for 24 hr. After 24 hr of storage, the block was reperfused with pooled venous blood for 10 min, and then with oxygenated blood for another 60 min in a closed circuit. Assessment of lung function included blood gas analysis of effluent blood, pulmonary artery pressure, airway pressure, wet:dry weight ratio, and histologic study.At flushing pressures of 5, 20, and 25 mmHg, uniform and clear flushing out of the pulmonary vascular beds was not obtained, resulting in postperfusion pulmonary hypofunction and a high incidence of pulmonary edema. However, at flushing pressures of 10-15 mmHg, we succeeded in completely flushing out the pulmonary vascular beds, and managed to preserve good pulmonary function. In conclusion, we determined the optimal flushing pressure for rabbit lung preservation to be 10-15 mmHg.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

We have shown that 24-hr preservation by a two-layer (University of Wisconsin solution [UW]/perfluorochemical [PFC]) cold storage method allows tissue ATP synthesis and makes it possible to resuscitate a canine pancreas subjected to 90 min of warm ischemia. The purpose of this study was to examine whether increasing preservation temperature to 20°C makes it possible to shorten a preservation period for recovery of ischemically damaged pancreas grafts. After 90 min of warm ischemia, canine pancreas grafts were preserved using the two-layer (UW/PFC) method for 1 to 8 hr at 20°C, and then autotransplanted. A K-value of intravenous glucose tolerance test more than 1.0 at 2 weeks after transplantation was considered graft survival. ATP tissue levels were measured by high performance liquid chromatography at the end of preservation. Pancreatic tissue perfusions were measured using an H2clearance technique after 30 min to 4 hr of reperfusion. Pancreas grafts subjected to 90 min of warm ischemia were not viable (0/5, control group). However, 3- and 5-hr preservations made it possible to recover the ischemically damaged pancreas (3/5 and 5/5, respectively), although 1- and 8-hr preservations were not successful (0/3 and 0/3, respectively). ATP tissue levels in 1-hr-preserved grafts were 2.55±0.38 μmol/g dry weight and were significantly lower compared with the levels in 5- and 8-hr-preserved grafts, 9.40±2.09 (P<0.01) and 7.37±1.06 (P<0.01), respectively. On the other hand, pancreatic tissue perfusions in 8-hr-preserved grafts after 2 hr of reperfusion were 28.50±7.52 ml/100 g/min and were significantly lower than the values in 1- and 5-hr-preserved grafts, 66.0±11.22(P<0.01) and 57.10±4.40(P<0.01), respectively. It was suggested that 1-hr-preservation was not enough to synthesize ATP, which was essential to repair damaged cells, although vascular microcirculation at reperfusion was maintained and 8-hr preservation incurred microcirculatory disturbances, although ATP for repairing damaged cells was synthesized. We conclude that 3- to 5-hr preservation at 20°C by the two-layer (UW/PFC) method accelerates ATP synthesis, which is essential for repairing damaged cells and protects vascular microcirculation. This makes it possible to resuscitate ischemically damaged pancreases faster. This method holds promise for pancreas-kidney transplantation from cardiac arrest donors.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effects of alternate-day (QOD) steroid dosing on growth, graft survival, and graft function in children with functioning grafts 12 months after transplantation. At 12 months after transplantation, 16.8% (337/2001) of transplant recipients were receiving QOD dosing. The basis for the selection of a steroid dosing regimen cannot be determined from registry data; however, the frequency of QOD dosing differed by donor source, race, age at transplant, and the occurrence of rejection episodes in the first year.The effect of the steroid dosing pattern on growth was evaluated in children continuously on either QOD or daily (QD) steroid dosing. The mean change in the standardized height scores from 1 month to 24 months after transplantation was significantly greater in those on QOD dosing(+0.5±0.06) than in those on QD dosing (+0.1±0.03). Using multiple regression analyses, better growth was associated with QOD dosing, recipient age less than 13 years, lower total steroid dose over 48 hr, and lower serum creatinine (allP<0.001).Graft survival did not differ on the basis of the steroid dosing pattern. In a proportional hazards model for survival of living donor grafts after 12 months, graft survival was negatively associated with the use of QD dosing, black race, rejection episodes in the first year, and a higher serum creatinine at 12 months. The survival of cadaver grafts was negatively associated with the use of QD steroid dosing, recipient age less than 2 years, rejection episodes in the first year, and a higher serum creatinine at 12 months. In addition, the decline in graft function did not differ between those on QOD steroid therapy and those on QD therapy.We conclude that selected pediatric renal transplant recipients receiving QOD dosing have better growth than those receiving QD dosing without compromising allograft survival or function.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4 years, we have set up a program of two-kidney transplantation from cadaveric infant donors under age 3 years, which to date includes 15 adult recipients. Thirteen of these grafts are currently functioning at least as well as those from adult donors, after a mean follow-up of 1.5 years. Our surgical and therapeutic procedures have led to a minimization of the early complications reported by other groups. With this transplantation procedure, the patients receive double the number of nephrons, which will probably give them better long-term function. The encouraging results achieved by our group may help change the current consideration of pediatric donors as “sub-optimal” ones.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

To assess the development, stability, and clinical relevance of donor-type microchimerism, skin and blood were analyzed in heart (n=53) and liver (n=18) transplant recipients by nested polymerase chain reaction. Microchimerism was detectable in 40 (75%) and 13 (72%) patients after heart and liver transplantation, respectively. In heart transplantation, chimerism-positive patients showed a lower frequency of acute rejection as compared with negative patients, although this was only of borderline statistical significance. Repeated intraindividual analyses demonstrated variable patterns of microchimerism over time, but changes did not correlate to the clinical state. In liver transplantation, chimeric state showed no clear correlation with the patients' immunological situation. Our results demonstrate that peripheral microchimerism frequently develops after different types of organ transplantation and represents a dynamic process but without diagnostic value to predict the immunological risk for individual patients.

ISSN:0041-1337    

出版商:OVID    

年代:1996

数据来源: OVID