CD11b在肺纤维化患者的表达及红霉素对其影响

目的探讨CD11b在肺纤维化患者外周血中性粒细胞上的表达及红霉素对它的影响.方法肺纤维化患者(A组,n=13)13例经红霉素治疗3个月,收集治疗前后及健康对照组(B组,n=13)13例的外周血中性粒细胞涂片,用桥联酶免疫法测定CD11b表达阳性的中性粒细胞百分率.结果A组治疗前后,患者外周血中性粒细胞CD11b的表达阳性率均显著高于健康对照组(P＜0.01);A组治疗前,患者外周血中性粒细胞CD11b的表达阳性率显著高于治疗后(P＜0.01).结论肺纤维化患者外周血中性粒细胞CD11b的表达阳性率显著高于健康对照组;红霉素能抑制肺纤维化患者外用血中性粒细胞CD11b的表达.     

原发性胃癌中MRE11基因的突变筛查

目的:研究染色体不稳定性相关基因MRE11(meiotic recombination 11 homolog A)突变与原发性胃癌的相关性。方法:收集27例原发性胃癌病人的胃癌组织和对应的正常胃黏膜组织,并通过显微切割方法从胃癌组织中获取较纯胃癌细胞。设计扩增MRE11基因外显子的引物共20对,采用PCR产物直接测序方法在胃癌细胞和对应正常胃黏膜组织中对MRE11基因编码区进行突变检测,并运用CGH方法对存在突变的胃癌细胞进行染色体分析。结果:在27例原发性胃癌中,4例存在MRE11基因共4个体细胞水平的错义突变,其中3例为肠型胃癌。CGH显示该4例胃癌均存在5个以上基因组片断的获得或丢失事件。结论:MRE11基因突变可能在某些原发性胃癌的发生发展中起着重要作用,尤其是显示染色体不稳定性的肠型胃癌。     

建立白介素-1β诱导小型猪冠状动脉狭窄动物模型

目的探讨建立快速、稳定冠状动脉狭窄程度符合临床干预治疗的动物模型方法。方法将小型猪40头随机分为5组,每组8头分别开胸手术,游离搔刮冠状动脉前降支和回旋支外膜并按组包裹含不同剂量白介素-1β(IL-1β)纸巾,IL-1β含量依次为0、3.0、4.5、6.0、7.5μg。术后2周行冠状动脉造影,观察局部冠状动脉狭窄病变情况,处死动物,对包裹纸巾的冠状动脉血管段行病理分析。结果冠状动脉造影见各组冠状动脉管腔平均狭窄程度依IL-1β剂量分别为0、20.61%、39.58%、77.34%、93.79%。IL-1β剂量7.5μg组中2头猪前降支100%狭窄,1头于术后11d死亡未作造影。组织病理学检查见含IL-1β纸巾包裹的冠状动脉血管内膜均有不同程度的增生、炎性细胞浸润、管腔缩小,增生的血管内膜内可见少量血管平滑肌细胞;不含IL-1β纸巾包裹的冠状动脉血管内膜和中膜无增生,管腔无变化。结论采用游离搔刮小型猪冠状动脉前降支和回旋支外膜并包裹含IL-1β6.0μg的纸巾,2周内可建立起稳定、可靠、狭窄程度符合临床冠心病干预治疗的实验研究动物模型。     

联合应用纳洛酮与甲基强的松龙对大鼠急性肺损伤的保护作用

目的　探讨联合应用甲基强的松龙、纳洛酮对内毒素所致急性肺损伤大鼠的防治作用及可能机制。方法　建立大鼠内毒素吸入性ALI模型 (LPS ,3mg/kg气管内注射 ) ,85只大鼠随机分为生理盐水对照组、内毒素损伤组、甲基强的松龙组 (内毒素 甲基强的松龙 )、纳洛酮组 (内毒素 纳洛酮 )、联合用药组 (内毒素 甲基强的松龙 纳洛酮 )。采用放射免疫方法检测大鼠血清TNF -α、IL - 8水平 ,并观察动脉血气分析及肺组织病理变化。结果　内毒素损伤组较生理盐水组TNF -α、IL - 8水平明显增高 ,动脉血氧分压明显降低 ,肺组织可见肿胀、淤血、炎细胞浸润。联合用药组各项指标较内毒素损伤组均轻。结论　联合应用甲基强的松龙和纳洛酮可降低气管内注入内毒素致大鼠ALI血清TNF -α、IL - 8升高水平 ,减轻肺损伤病理改变程度 ,对大鼠ALI有防治作用     

Decreased Risk of Renal Allograft Thrombosis Associated With Interleukin-2 Receptor Antagonists: A Report of the NAPRTCS

Graft thrombosis is the most common cause of first year graft failure in pediatric renal transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database was analyzed for cases of graft failure due to thrombosis among patients transplanted from 1998 to 2004. The impact of interleukin-2 (IL-2) receptor antagonists as induction therapy was determined. There were a total of 51 graft failures due to thrombosis among the 2750 reported renal transplants (1.85%) (95% CI (1.39%, 2.41%)). This represents the most common cause of graft loss during the first year post-transplant accounting for 35% of first year losses and 18% of all graft losses. The incidence of thrombosis among patients who received IL-2 receptor antibodies was 1.07% (12/1126) compared to 2.40% (39/1624) among patients who did not (OR 0.44, 95% CI 0.23, 0.84, p = 0.014). Use of IL-2 receptor blockade was the only significant prognostic factor in a multivariate model with previously identified risk factors. Analysis of NAPRTCS data found that the use of IL-2 receptor antibodies as induction therapy is associated with a significantly decreased risk of graft failure due to thrombosis. This provocative finding requires further investigation to determine whether thrombotic failure can be decreased by this therapeutic strategy.     

Effect of electro-acupuncture combined with early rehabilitation on motor function and expressions of CD11b/CD18 and tumor necrosis factor-α in patients with acute cerebral infarction

Objective To observe the effect of electro-acupuncture combined with early rehabilitation on the motor function and expressions of the adhesion molecules CD11b and CD18 in the polymorphonuclear leucocytes (PMN) and monocytes and serum tumor necrosis factor-α (TNF-α) levels in patients with acute cerebral infarction (ACI). Methods A total of 165 ACI patients were randomly divided into control group (group A, n=50), conventional rehabilitation group (group B, n=50) and comprehensive rehabilitation group (group C, n=65). The expressions of CD11b and CD18 in the PMN and monocytes and serum TNF-α levels were determined before and at 1, 2, and 4 weeks after the treatment. Thirty-two healthy subjects were also recruited as the normal control group (group N). The neurological function of the subjects was evaluated by modified Edinburgh-Scandinavia stroke scale (MESSS) and Fugi-Meyer Assessment (FMA), and their activity of daily living (ADL) was assessed using Barthel index (BI). Results The CD11b/CD18 expression in the PMN and MN and serum TNF-α level in groups A, B and C were significantly higher than those in group N before and 1 week after the treatment (P<0.05). CD11b/CD18 expression and serum TNF-α level were significantly lower in groups B and C than in the group A at 1 week after the treatment, and significantly lower in group C than in group B (P<0.05). At 2 weeks of treatment, CD11b/CD18 and TNF-α were significantly lower in groups B and C than in the group A, being the lowest in group C (P<0.05). The scores of mESSS in both groups B and C were lower than that in group A, and the scores were lower in group C than in group B. Group C showed higher FMA scores than group B, both having higher scores than group A. At 4 weeks of treatment, the mESSS scores were significantly lower, hut the FMA and ADL score significantly higher in groups B and C than in the control group (P<0.05), and the differences were more obvious in group C. Groups B and C had greater effective rate than group A (P<0.05), and the rate was the highest in group C (P<0.05). Conclusion Electro-acupuncture combined with early rehabilitation promotes the recovery of motor function in ACI patients probably by regulating the expressions of the adhesion molecules CD11b and CD18 on the PMN and monocytes and the serum levels of TNF-α.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

多发性硬化患者中IL-12和孕酮的检测及其临床意义

目的检测IL-12和孕酮在多发性硬化(MS)患者中的水平,探讨男、女性多发性硬化患者存在的发病机制,比较男、女性MS患者在临床上发病的差异。方法采用酶联免疫(ELISA)法检测60例MS患者的脑脊液和40例患者血液中IL-12的水平,应用放射免疫法测定40例MS患者血液中孕酮的含量,并与40例正常对照组比较(以上标本男女各半)。结果男、女性MS患者血液中和脑脊液IL-12的含量明显高于正常对照组(P<0.01);女性患者血液中孕酮的含量明显低于正常对照组(P<0.01),男性患者血液中孕酮的含量与正常对照组差别不明显(P>0.05);女性患者血液中孕酮对IL-12的含量存在负相相关作用(r=-0.80,P<0.01),男性相关作用不明显(r=-0.38,P>0.05)。结论IL-12参与多发性硬化的发病过程;孕酮可能是男、女性患者发病差异性的原因之一。     

新的高强度高选择性阿片μ受体激动剂[11C]-羟甲芬太尼的合成

羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[¹¹C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[¹¹C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[¹¹C]-丙酰氯。[¹¹C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[¹¹C]-羟甲芬太尼;[¹¹C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[¹¹C]-羟甲芬太尼。两种方法均可获得ll.1～14.8GBq/μmol的特异性放射化学纯[¹¹C]-羟甲芬太尼。总共耗时为40～50min(EOB)。     

Monocyte adhesion molecule expression in interstitial inflammation in patients with renal failure.

BACKGROUND: Patients with renal failure have an increased susceptibility to infections. We therefore studied the recruitment of monocytes and their expression of adhesion molecules CD11b and CD62L at the site of interstitial inflammation in patients with renal failure. Furthermore, we studied if the capacity of monocytes to up-regulate CD11b in interstitial inflammation was determined by the interstitial concentration of chemotactic factors. METHODS: Three intensities of interstitial inflammation (0, intermediate and intense) were established in skin blister chambers. Leukocyte count, CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1) and blister activity in terms of CD11b mobilization were determined. RESULTS: The CD62L expression on monocytes was lower in the peripheral circulation in patients with renal failure compared with healthy subjects (P<0.005 and P<0.001). At the site of interstitial inflammation patients had a higher expression of CD62L (intermediate, P<0.05; intense, P<0.005). Furthermore, monocytes from patients had an impaired capacity to mobilize CD11b both in the peripheral circulation (P<0.005) and at the intermediate and intense sites of interstitial inflammation (P<0.005 and P<0.001, respectively) compared with cells collected from healthy subjects. We incubated monocytes in blister exudates, in order to explore whether this phenomenon is caused by cellular factors and/or to the interstitial concentration of chemotactic mediators. The expression of CD11b on monocytes from healthy blood donors incubated in blister exudates from either patients or healthy subjects in vitro was similar. The interstitial concentration of MCP-1 at the site of intermediate inflammation was significantly lower in patients with renal failure compared with the corresponding blister exudate collected from healthy subjects (P<0.05), but no differences were observed at the site of intense inflammation. Furthermore, neutralizing the action of MCP-1 in blister exudates with monoclonal antibodies did not have any impact on monocyte CD11b expression following incubation in blister exudates. CONCLUSION: These studies indicate that the impaired capacity of monocytes to mobilize CD11b at the site of inflammation in patients with renal failure is more dependent on constitutive cellular factors than the concentration of CD11b mobilizing factors in the interstitium.