摘要:

These experiments describe a murine model for survival and engraftment of bone marrow transplantation across differing histocompatibility barriers. Anti-Thy-1.2 antibody and complement-treated C57BL/6 (B6) marrow was transplanted at varying cell dose levels into syngeneic (B6), major histocompatibility complex congenic (A.BY), semiallogeneic (B6AF1), and fully allogeneic (A/J) recipients. Survival was monitored and engraftment determined by hemoglobin and lymphocyte phenotype. Survival was cell-dose dependent and was equivalent in B6, A.By, and B6AF1recipients. Survival was poor in allogeneic A/J recipients due to bone marrow failure even at high marrow dose levels. Survival posttransplant did not always correlate with stable donor engraftment, and competitive host marrow repopulation was frequently seen in B6AF1recipients but rarely in A.BY recipients. This repopulation could be prevented by transplanting a larger marrow dose.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Eleven rat livers were stored at 7°C for 24 or 48 hr using a continuous nonpulsatile perfusion method. The perfusate was based on the isotonic citrate preservation solution but contained, in addition, gelatin polypeptides (Haemaccel, Hoechst) and fluorocarbon emulsion (FC-43, Green Cross Corp.).Isologous livers were orthotopically transplanted after preservation, and long-term survival was 3/6 following 24 hr preservation and 4/5 following 48 hr preservation. All the biopsies taken immediately after re-vascularization were histologically normal. The seven surviving animals were killed at two months and histology showed biliary obstruction, but in all cases the hepatocytes appeared to be well preserved. These late histological findings are common in any use of this transplantation model and are believed to be associated with the difficulty of obtaining a satisfactory anastomosis of the bile duct.The perfusate described here is capable of providing reliable 48 hr preservation of the rat liver.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Alterations in local prostacychn and thromboxane synthesis could mediate the changes in vascular perfusion and platelet deposition in acutely rejecting renal allografts and prostaglandin E2(PGE2) has been implicated in the regulation of the immune response.6-Keto-prostaglandin F1alpha(6 KetoPGF1alpha), thromboxane B2(TxB2) (the stable degradation products of prostacyclin and thromboxane A2[TxA2], respectively) and PGE2were measured in incubates of cortical slices taken from rat renal allografts or isografts one to seven days after transplantation. 6 KetoPGF1alphaand TxB2synthesis was also measured in incubates of blood vessels supplying and transplanted with the kidney in these animals.During the phase of cellular rejection (3–5 days), TxB2synthesis was selectively elevated in allografted renal cortex, renal artery, renal vein, and abdominal aorta in comparison with isografted tissues. There was also a small but significant rise in cortical PGE2synthesis at this time, but vascular and cortical 6 KetoPGF1alphaproduction remained unchanged. Renal infarction, occurring 7 days after transplantation, was accompanied by a nonspecific rise in the synthesis of all three prostaglandins by renal cortical slices. Increased tissue TxA2synthesis may contribute to local thrombosis and decreased graft perfusion during acute rejection, thereby potentiating graft destruction.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Inbred strains of rats were used to analyze unidirectional host-versus-graft disease (transplant rejection) without graft-versus-host disease in small intestinal transplants and the immunosuppressive properties of cyclosporine (CsA). Forty-six Lewis rats received heterotopic transplants of the entire small bowel in four groups: (1) Lewis-to-Lewis isografts, without CsA; (2) Lewis-to-Lewis isografts, with CsA (15 mg/kg/day); (3) (Lewis × ACI)F1-to-Lewis allografts, without CsA; (4) (Lewis × ACI)F1-to-Lewis allografts, with CsA. Small bowel rejection was associated with gross morphological changes that preceded all other findings. A histologic scoring system assessed the degree of transplant rejection. A characteristic transient weight loss was seen in animals rejecting their bowels. Glucose absorption was impaired and polyethylene glycol absorption increased during rejection. Cyclosporine inhibited all of these changes in allografted rats. It is concluded that daily administration of cyclosporine is effective in preventing the morphologic and functional changes of acute transplant rejection in intestinal allografts and does not change these parameters in transplants that are not rejecting.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Brattleboro rats manifest chronic diabetes insipidus as a result of the genetic deficiency of hypothalamic vasopressin. When basal hypothalamic tissue derived from adult F344 rats was implanted as cell suspensions or tissue blocks in the supraoptic regions of these animals, concentration of urine together with reduced urine output and water intake was observed in some animals. Histologic examination of the grafted brains from the responding animals revealed neuronal cells at the implant sites and vasopressin-staining fibers in the median eminence. This study demonstrates the feasibility of the grafting of adult cerebral tissues to correct a genetic hormonal deficiency.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Clearance studies were performed in 32 transplanted children treated with CsA in combination with low-dose prednisolone (CsA group), and the results were compared with those of 29 children transplanted earlier and treated with azathioprine and prednisolone (CIS group). Serum creatinine and urea levels 6 weeks and 1 year after transplantation (Tx) were significantly higher in the CsA than in the CIS group. Clearance studies 6 weeks after Tx exhibited significantly lower rates in the CsA group: Cin = 47+/-16.5 versus 83+/-25 ml/ min/1.73 sqm, CPAH = 271+/-110 versus 503+/-181 ml/min/1.73 sqm (P<0.001). The filtration fractions were not different (19.1 versus 17.1%). The tubular phosphate reabsorption per ml GFR (Tp/Cin) was only slightly lower in the CsA group (0.76+/-0.23 μmol/ml versus 0.93+/-0.29; P=0.09). The endogenous glucose clearance rates were equally elevated in both groups and returned to normal after 1 year. The creatinine clearance (Ccr) had dropped in both groups by a mean for 13 ml/min/1.73 sqm between 6 weeks and 1 year after Tx. No correlation was found between the Ccr and the CsA blood levels, but Ccr was inversely correlated with the number of rejection episodes (r= −0.72, P=0.001).In conclusion, renal allografts in CsA-treated children exhibited a significantly lower function than in CIS-treated children. The effect was related to the global kidney function without any signs of additional tubular toxicity and was apparent within the first weeks after Tx. Thereafter, the decline in graft function was comparable in both groups and could not be related to CsA treatment.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The following investigation was performed to establish whether renal transplant patients treated with cyclosporine and prednisone have a decreased prednisolone catabolism and/or an increased systemic availability of oral prednisone when compared with patients treated with azathioprine and prednisone. Therefore we assessed, by HPLC and equilibrium dialysis, the total concentrations of prednisolone and prednisone and the unbound concentrations of prednisolone in plasma samples collected over 24 hr, and the 24-hr urinary excretion of prednisolone, prednisone, and 6β-hydroxyprednisolone after an i.v. dose of prednisolone and an equal oral dose of prednisone in 25 renal transplant patients on cyclosporine and in 25 patients on azathioprine and prednisone one month after transplantation. The metabolic clearance, the renal clearance, the volume of distribution, and the systemic availability of total and unbound prednisolone were identical in patients with and without cyclosporine. The apparent activities of the ox-idoreductases involved in the biotransformation of prednisone into prednisolone and vice-versa were not affected by cyclosporine therapy. The fractional urinary excretions of 6β-hydroxyprednisolone increased with increasing metabolic clearance rate of prednisolone (r=0.50, P<0.001). This relationship was not modulated by cyclosporine, indicating that cyclosporine does not affect the activity of the microsomal P-450-dependent 6β-hydroxylase. Thus, early after transplantation, patients on cyclosporine have a normal metabolism of prednisolone.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The role of pretransplant transfusion in cardiac allograft recipients was determined retrospectively in 68 patients. Three groups were studied: group 1 (n=29) received no pretransplant transfusion, group 2 (n=15) received transfusion over one year prior to transplantation, and Group 3 (n=24) received 5 or 10 50–100 ml units of random donor red blood cells or buffy coat 2–4 weeks prior to transplantation. Data were analyzed for survival, number of rejection episodes, and number of infections. Immunosuppression included azathioprine, prednisone, and antithymocyte globulin. Survival in transfused patients (groups 2 and 3) was 68% and 51% at 1 and 5 years, respectively, while in the nontrans-fused population (group 1) it was 35% and 16%. The incidence of rejection episodes per year of survival was similar in the three groups (group 1: 1.3, group 2: 1.1, group 3: 1.3; P<0.05). The number of infections per year of survival were greater in the transfused patients but this did not achieve statistical significance (group 1: 1.0, group 2: 1.2, group 3: 1.7; P<0.05). Thus, we conclude that cardiac transplant recipients who have received blood transfusions prior to transplantation may have enhanced survival over patients who have not received preoperative transfusions.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The recent introduction of a variety of techniques for removing T cells from bone marrow grafts has reduced the incidence of graft-versus-host disease (GVHD)*-associated morbidity and mortality (1–4). Whether this advance will be translated into improved patient survival is unclear at present, mainly because these procedures increase the risk of graft failure (2, 5,6).Since 1983 we have transplanted 25 consecutive leukemia patients with HLA-identical sibling grafts purged of T cells by a single incubation with the monoclonal antibody Campath-1 and donor complement (7). This approach was successful in reducing T cell contamination of the graft and preventing acute and chronic GVHD. In this group of patients two suffered irreversible graft failure and one developed reversible graft failure. In a similarly sized group of patients previously transplanted with unpurged marrow according to the Seattle protocol, no episodes of graft failure occurred (8). Since other causes of graft failure, such as drug toxicity or viral infections, could be largely excluded, this suggested that the graft failures were specifically related to the purging process.In haploidentical bone marrow transplantation (BMT) O'Reilly has identified residual host-versus-graft activity (HVG) as a cause of graft failure (9). The causes and mechanisms of graft failure in T-depleted HLA-identical sibling transplants have not been extensively investigated to date. In the three graft failures observed by us, the loss of the graft was preceded by the appearance of a population of activated lymphocytes. We have determined the phenotype and origin of this population and investigated its interactions with donor hemopoietic tissue in vitro.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

In a randomized controlled clinical trial, 117 recipients of a kidney transplant were treated with cyclosporine (15–17 mg/kg/day) either alone or with prednisolone 0.3 mg/kg/day in addition. There were no exclusions and all patients have been followed-up from 14 to 39 months. No differences in the survival of the patients or their transplants were seen between the two groups. Actual survival of first cadaver grafts was 73% at one year in the group receiving cyclosporine alone and 76% in the group with added steroids. Survival of second or third grafts in the steroid group was somewhat worse but not significantly so. All 6 recipients of living-donor grafts are currently alive with good function. Infective complications were significantly less common in the group not receiving routine steroids, and these patients were also at less risk of developing a changed facial appearance. However, half the patients in this group have subsequently required steroids because of previous rejections, and cyclosporine nephrotoxicity has been significantly more common. Nonetheless, we have found no overall advantage in combining cyclosporine with low-dose maintenance prednisolone, and we advise that patients undergoing renal transplantation receive cyclosporine alone in the first instance.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID