A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

中华眼镜蛇蛇毒对大鼠异种心脏移植超急性排斥反应的影响

试用中华眼镜蛇蛇毒消耗补体，观察其对豚鼠到ＳＤ大鼠异种心脏移植超急性排斥反应的影响。一次性给予小剂量ＣＣＶ腹腔注射后可明显降低大鼠血清补体溶血活性，４－２４小时后渐降至给药前１／２以下水平。ＣＣＶ可明显延长异种移植心脏４ 存活时间达２．５－３６小时，对照组仅为２５分钟；ＣＣＶ与脾切除，前列腺素Ｅ１联用可进一步延长移植心的存活时间，最长１例达４０小时。     

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1–5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6–12 and 12–17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.A list of all participating centers and the names of the investigators is printed on pages 552–553     

In vitro and in vivo effects of BT563, an anti-interleukin-2 receptor monoclonal antibody

Abstract BT563, a murine anti-IL-2R MoAb, was found to be more potent than anti-Tac in inhibiting proliferation in the mixed lymphocyte reaction. Results obtained with 33 B3.1 in these experiments were similar to those with BT563. The anti-IL-2R MoAb 2A3 was shown to be a suitable agent for monitoring the effect of BT563 on peripheral blood. IL-2R-positive cells were not detected in peripheral blood samples from 1 h after the first dose until 8 days after the last dose. Plasma trough levels were measured in patients receiving 5 or 10 mg daily. The administration of BT563 to allograft recipients did not lead to clinically significant side effects.     

Adjuvant treatment with ursodeoxycholic acid reduces acute rejection after liver transplantation

Acute rejection, occurring with a reported frequency of 50–70%, is still a dominating problem after liver transplantation. Medication with ursodeoxycholic acid (UDCA) has beneficial effects in different cholestatic conditions and has also been shown to reduce HLA class I antigen expression on hepatocytes in patients with PBC. Since August 1989 we have consecutively treated all patients with primary graft function with UDCA (n = 41). Patients transplanted in the first half of 1989 served as a control group (n = 8). All patients in this study were given sequential quadruple drug immunosuppression. The treatment group were given oral UDCA 10 mg/kg per day. During the first postoperative month, 17% of the UDCA-treated patients had an episode of acute rejection compared with 75% of the control patients (P < 0.01). Liver biochemistry tests 1 month postoperatively were significantly better in patients treated with UDCA. The results suggest that adjuvant treatment with UDCA reduces acute liver graft rejection.     

Receptivity,rejection and reactivity in female rats following kainic acid and electrolytic septal lesions

Sprague-Dawley rats were ovariectomized and received bilateral sham, electrolytic or kainic acid lesions of the septum. Kainic acid lesions are purported to destroy cell bodies while not appreciably damaging fibers of passage or afferent terminals. Following priming with estradiol benzoate (EB), animals received three consecutive tests of lordosis and rejection behavior. Animals also received six tests of reactivity; one prior to each EB priming regimen and one following each lordosis and rejection test. Reactivity measures included resistance to capture and magnitude and quantity of startle responses. Electrolytic and kainic acid lesions were equivalent in facilitating lordosis. Although both lesions also increased rejection frequency, kainic acid effects were transient and markedly smaller by 60–80%. Reactivity data generally demonstrated significantly higher scores for kainic acid and electrolytic lesions groups and apparently time-dependent decreases in these scores. The results suggest that rejection behavior is not necessarily correlated with either lordosis or hyperreactivity.     

Role of HLA molecular mismatch in clinical practice

To date, traditional pre-transplant risk factors have failed to provide accurate risk stratification in transplantation. As a result, the practice of precision medicine remains elusive, resulting in a one-size-fits-all therapeutic approach for most patients. However, recent advancements in the understanding of HLA molecules at the molecular level have revitalized interest in HLA mismatch assessment. This review discusses HLA molecular mismatch as a potential prognostic and predictive biomarker available at the time of transplantation and answers some of the common questions and critiques of this approach. We highlight the retrospective data that supports single molecule risk categorization and explore the next steps required to evaluate its potential in clinical practice.     

环孢霉素A滴眼预防高危角膜移植免疫排斥的效果

目标 探讨环孢霉素Ａ（ＣｓＡ）联合地塞米松局部滴眼预防高危穿透角膜移植（ＰＫＰ）免疫排斥反应的效果。方法 将７７眼高危ＰＫＰ分为ＣｓＡ组（３７眼）;２％ＣｓＡ蓖麻油溶液联合地塞米松滴眼;对照组（４０眼）单独使用地塞米松滴眼。采用生存曲线进行比较。结果 术后２年,两组植片存活率分别为８９％和６０％,差异有显著性（Ｐ〈０．０５）。结论 ２％ＣｓＡ蓖麻油溶液联合地塞米松溶液局部滴眼是预防高危ＰＫＰ免疫排     

Bcl-2基因转染对心脏移植排斥反应中心肌细胞凋亡的影响

目的　探讨Bcl-2基因转染对心脏移植排斥反应中心肌细胞凋亡的影响。方法　采用小鼠颈部心脏移植模型 ,随机分为 3组 :对照组、移植组、Bcl-2组。分别于术后第 1、3、5、7d各取 4只移植心脏 ,原位末端标记 (TUNEL)法染色检测心肌细胞凋亡 ,以心肌细胞凋亡阳性细胞数占总心肌细胞数的百分比作为心肌细胞凋亡指数 (apoptosisindex ,AI)。用免疫组化方法观察Bcl -2的表达情况。结果　移植组心肌细胞于术后第 1d即已出现凋亡 ,第 3d明显增加 ,第 7d达高峰。Bcl-2组术后第 1d心肌细胞即表达Bcl -2 ,第 3d表达明显增加 ,第 5d达高峰 ,第 7d仍维持高峰状态。Bcl -2组各时间点心肌细胞凋亡指数明显小于对应的移植组(P <0 0 1)。结论　Bcl -2基因转染对心脏移植排斥反应中心肌细胞凋亡有显著抑制作用