摘要:

Periodic assay of IL-2 receptor expression on the surfaces of peripheral blood lymphocytes might provide information predictive of in vivo immunologic events. This study compares two methods of determining IL-2 receptor expression after renal transplantation in cynomolgus monkeys. The first utilized single color staining of peripheral blood mononuclear cells with mouse anti-human IL-2 receptor monoclonal antibody followed by a fluorescein-labeled goat anti-mouse IgG antibody. Epics C cell sorter windows were set to count cells of the size and granularity of normal lymphocytes. The second utilized two-color staining with fluorescein-labeled anti—IL-2 receptor antibody, combined with phycoerythrin-labeled anti-CD4 antibody or with phycoerythrin-labeled anti-CD8 antibody. Two-color staining allowed the sorter windows to be enlarged to count all mononuclear cells, regardless of size or granularity, without introducing the contaminating effects of monocytes. Data obtained from single-color staining showed no consistent or significant expression of the IL-2 receptor on peripheral lymphocytes in association with the rejection process. Data obtained from two-color staining revealed an increase of IL-2 receptor expression on peripheral T cells of at least 10% from the postoperative baseline, which preceded the creatinine rise from allograft rejection in 13 of 13 animals. Increases in IL-2 receptor expression on T cells were not specific to rejection, however. Some animals in which treatment produced a delay of rejection showed a transient rise in IL-2 receptor expression around post-transplant day 5, which was not followed by a rise in creatinine. The two-color staining technique described provides a sensitive means of detecting IL-2 receptor expression in vivo and documents the association of increases in IL-2 receptor expression on T cells with rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Anti—interleukin-2 receptor monoclonal antibodies have been shown to prevent allograft rejection. This paper reports on the biodistribution of a mouse MoAb directed at the 55 Kd alpha chain of rat interleukin-2 receptor (IL2-R) during allograft rejection. Only a low percentage (1%) of intact 125 I-labeled MoAb was detected in the rejected graft, and irrelevant control IgG1 was found at a similar level. This suggests that most of the injected intact MoAb bound to graft tissue via its monomorphic Fc segment. In contrast, OX39 F(ab')2fragments showed a preferential localization in the rejected allograft and did not bind to the LEW-to-LEW syngeneic heart graft. Irrelevant F(ab')2did not concentrate in the allogeneic graft. Accordingly, F(ab')2fragments from OX39 or irrelevant MoAb were used for gamma-scintigraphy on allograft recipients together with biodistribution studies. Results show that scintigraphy was able to detect allograft accumulation of 131 I OX39 F(ab')2, whereas no imaging was obtained when OX39 F(ab')2was used in the syngeneic combination or when irrelevant 131 -IgG1F(ab')2was given to allograft recipients. This method, applied to the clinical situation, could be of interest for detection of early graft rejection episodes by immunoscintigraphy using reagents specific for activation determinants on lymphocyte membranes, such as anti-interleukin-2 receptor MoAb.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Corneal grafts are believed to enjoy a degree of “immunological privilege” primarily due to the avascularity of the recipient bed. In this study orthotopic full-thickness corneal grafts were carried but in the inbred rat, using a technique that is a close model of corneal grafting in humans.The survival times of corneal grafts on nonvascularized beds of 28 fully allogeneic strain combinations were determined without the use of immunosuppression. Some combinations were rejected rapidly, e.g. DA (RT1a ) into BN (RT1n ) with a mean survival time (MST) ±SD of 7.8±1.3 days, and some at a moderate rate, e.g. AO (RT1u ) into LEW (RT1I ) with an MST of 23.1±10.0 days, whereas in other cases survival was indefinite, e.g. WAG (RT1u ) into PVG (RTFc ), an MST of >100 days.Orthotopic corneal grafts on nonvascularized beds between DA and AO parents and the F1, followed the basic rules of transplantation genetics. In addition, the rate of graft rejection was significantly faster (P<0.001) with corneal grafts from DA into AO placed onto a vascularized compared with a nonvascularized corneal bed (MST of 6.8±2.4 or 12.1±4.0 days respectively). The rate of rejection of corneas on a vascularized bed was at a similar rate to that of orthotopic skin or heterotopic auxiliary heart grafts.The results indicate that the fate of a corneal allograft on a nonvascularized bed is dependent upon the particular combination of donor and recipient strain. No consistent association was observed between any donor or recipient RT1 haplotype and survival; this suggests that non-RT1 background genes may play a role in the survival of corneal grafts.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We have studied the reliability of serum and urinary immunoreactive anionic trypsin (irAT), immunoreactive cationic trypsin (irCT), and amylase activity as rejection indicators in a porcine whole-organ pancreaticoduodenal transplantation model with exocrine drainage to the urinary bladder. No immunosuppressive therapy was administered. Exocrine tissue integrity and function were studied by measuring these enzymes in serum and urine. Urine analyses were performed before and after an intravenous secretin-cholecystokinin stimulation.Of 16 transplanted pigs, 10 became diabetic during a 2-week observation period while six remained normoglycemic. Serum irAT was found to predict rejection while serum amylase and serum irCT did not. An increase in irAT was seen in rejecting pigs preceding the onset of hyperglycemia by a median of 2 days (range 1–9). Secretion of irAT into the urine remained high during the observation period in nondiabetic pigs while the output declined in diabetic pigs. This decline was seen after the increase in serum irAT. When urine was sampled after a secretin-CCK stimulation, these findings were clearly evident, but less unequivocal results were obtained without stimulation. IrAT measurements were superior to measurements of amylase, irCT, or bicarbonate.Thus rejection of a pancreatic allograft was first indicated by a temporary rise in serum immunoreactive anionic trypsin, probably due to the onset of tissue damage. Thereafter, stimulated urinary enzyme output levels gradually declined and finally, hyperglycemia developed.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Cyclosporine was fed to male Wistar rats in a dose of 5, 10, or 50 mg/kg b.wt. for 7 days, and the effect on insulin secretion from the isolated perfused pancreas was investigated. Dose-dependently plasma insulin and pancreatic insulin content decreased while whole-blood CsA levels increased. An increase in blood glucose was only observed after feeding 50 mg/kg b.wt. CsA resulting in whole-blood CsA levels of 7735 ng/ml. Glucose (20 mM)-stimulated total insulin secretion (ng/50 min) was not affected during feeding 5 mg/kg b.wt. CsA, but was significantly reduced after feeding 10 or 50 mg/kg b.wt. CsA. The biphasic insulin secretion was reduced after 5 mg/kg b.wt. during the initial peak (0–10 min) but not during the second peak (10–50 min), whereas after 10 or 50 mg/kg b.wt. CsA both peaks were markedly reduced. The arginine (20 mM) and the arginine (20 mM)-plus-glucose (20 mM) stimulated insulin secretion was less affected after feeding 10 mg/kg b.wt. CsA than after stimulation with glucose (20 mM) alone. The addition of CsA to the perfusate did not influence glucose-stimulated insulin release from normal rat pancreas.Our results demonstrate a toxic effect of CsA on the pancreatic beta cell that is dose dependent and possibly influences both insulin secretion and biosynthesis.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

A model of rejection and regeneration of peripheral nerve allografts in rats is presented. A 2.5-cm segment of 28 right sciatic nerves was transplantated orthotopically from LEW.1W to DA and from DA to LEW.1W. With a microsurgical technique, proximal and distal coaptations were performed. In an autologous control group the same surgical procedure was applied. Evaluation included clinical estimation of motor recovery and macroscopic appearance of the graft, electrophysiological examination, conventional histology, and immunohistology. The latter concentrated on demonstration of monomorphic and polymorphic determinants of MHC class I and II antigens and of macrophages. By functional, electrophysiological, and histological parameters it was demonstrated that after rejection a certain degree of regeneration took place in the allografts. Both rejection and subsequent regeneration were studied in detail by immunohistology. During the course of Wallerian degeneration MHC class I expression on myelin sheaths could be demonstrated. When the rejection response occurred, additional MHC class II expression on myelin sheaths and on vascular endothelia was observed. Recipient specific class I–positive macrophages were infiltrating the graft from the epineurium and the coaptation sites, and were later present at the sites of myelin degradation. At 6 weeks postoperatively donor-specific MHC products were no longer detectable, but recipient-specific Schwann cells were present in the allograft tissue.We conclude that a rejection response renders a peripheral nerve allograft acellular but does not destroy the nerve architecture, still enabling it to function as an axon conduit. The regeneration in the rejected allograft however lacks the positive neurotropic and -trophic influence physiologically provided by viable Schwann cells.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Previous studies showed the beneficial effects of superoxide dismutase ± catalase in perfusion-preserved rabbit kidneys but failed to show benefit in flush-cooled organs. The current studies undertook to evaluate scavengers, xanthine oxidase inhibitors, and agents that prevent the release of myeloperoxidase in 3 systems: kidneys preserved by perfusion or by flush cooling for 24 hr, studied immediately, and warm ischemia-injured kidneys evaluated after a 24-hr recovery period. In none of these groups could we demonstrate any protective effects against preservational or warm ischemic injury by the above modalities. Even though biochemical and other evidence from previous studies suggested free radical-induced injury to occur in preserved rabbit kidneys, these studies using renal function as the indicator did not do so.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

During hepatic resection, occlusion of the hepatoduodenal ligament has been frequently applied to prevent intraoperative bleeding. To reduce hepatocellular ischemic damage in this procedure, we pretreated animals with Aprotinin. Three hours after an intravenous injection of 40,000 KIU Aprotinin in SD rats, we occluded the afferent hepatic vessels for 50-min and 60-min periods. 92% of occluded animals could sustain life after 60 min. Without premedication only 17 of 25 animals (68%) survived the 50-min occlusion, and 18 of 32 (56%) the 60-min occlusion. Biochemical analysis of sera was carried out 12 hr after a 40− and 60-min occlusion of the hepatoduodenal ligament with Aprotinin pretreatment. Furthermore we induced compensatory cirrhosis by application of CCL4and biochemical analysis of sera was carried out after a 30-min occlusion. The elevation of SGOT and SGPT values was drastically reduced in the animals with Aprotinin medication in comparison with those without treatment. These observations suggest the highly protective effect of Aprotinin in the case of warm ischemic hepatic damage, especially in the cirrhotic liver.After pretreatment of LEW rats with Aprotinin (40,000 KIU i.v.), we perfused the livers with chilled Ringer solution containing 40,000 KIU Aprotinin/20 ml. We transplanted the livers orthotopically into LEW rats. With the application of Aprotinin liver preservation time increased to 10–15 hr. However, without Aprotinin the livers could be successfully preserved for only 4–6 hr. Our results indicated that premedication with high doses of Aprotinin provided highly protective effects against warm and cold ischemic damage of the liver.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The purpose of this study was to evaluate the value of additive components and colloid included in the University of Wisconsin (UW) solution. Therefore, this solution was compared with a solution consisting of the basic components of the UW solution (potassium lactobionate, raffinose, phosphate buffer and MgSO4). We employed a method of measuring the amount of chromium-51-labeled erythrocyte trapped in the medullary vascula-ture 20 min after reperfusion of kidney grafts cold-stored for 24–48 h in either the basic UW (bUW) or the original UW (oUW) solution. The amount of trapping has been shown to correlate well with the degree of cold ischemic injury. Both hemodiluted (hct 20–27%) and normal (hct 41–45%) recipients were used. Long-term viability of grafts stored in either bUW or oUW was investigated in survival experiments and the flow rates during in situ flush-out were also measured, as well as weight changes during the storage period.The results showed no significant difference between the two solutions, regardless of ischemia time or whether hemodiluted or normal recipients were used. However, the flow rate and weight measurements showed that flushing was more rapid and kidney swelling less pronounced using oUW. Survival rates in longterm transplantation experiments were similar. It was concluded that the inclusion of a colloid improves the rheological properties of the UW solution and that the additives besides the basic components did not offer any advantage.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We present two instances of pancytopenia in kidney transplant patients associated with a course of OKT3 therapy. In one case, OKT3 was used prophylactically, in the other therapeutically to treat biopsy-proved rejection. They both occurred in the setting of multi-drug immunosuppression, including Minnesota anti-lymphocyte globulin, and recovered with supportive therapy. Previous antihypertensive medication, antibiotics, and azathioprine were restarted without hematologic sequelae. Evidence implicating OKT3, and resultant gamma-interferon—induced marrow suppression is discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID