The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an "activation state." In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.     

Relationship between disease severity and inflammatory markers in cystic fibrosis

To evaluate the clinical use of measuring neutrophil, lymphocyte, and eosinophil activities, serum myeloperoxidase (MPO), soluble interleukin-2 receptors (sIL-2R), and eosinophil cationic protein (ECP) were measured in 98 patients with cystic fibrosis and in 85 healthy children. Serum concentrations of MPO, sIL-2R, and ECP were increased in patients with cystic fibrosis (median 807 micrograms/l, 4452 pg/ml, 48.8 micrograms/l, respectively) compared with the controls (median 319 micrograms/l, 2743 pg/ml, 9.4 micrograms/l). ECP concentrations, but not serum MPO or sIL-2R, were significantly related to disease severity assessed by the Shwachman-Kulczycki score and by pulmonary function (forced expiratory volume in one second % predicted). Neither ECP nor sIL-2R was influenced by Pseudomonas aeruginosa infection, acute pulmonary exacerbation, or atopy. Serum MPO, however, was strongly correlated with acute pulmonary exacerbation. In the light of these findings the measurement of serum ECP might thus be used for clinical monitoring and for assessing disease severity in cystic fibrosis. The measurement of serum MPO and sIL-2R did not correlate with the disease severity.     

完全去神经大鼠皮肤愈合过程中神经纤维再生和降钙素基因相关肽的变化

目的:观察完全去神经对大鼠皮肤伤口愈合的影响及愈合过程中神经纤维再生和降钙素基因相关肽的变化情况,探讨神经纤维再生和降钙素基因相关肽与伤口愈合的关系。方法:实验于2006-02在北京大学人民医院中心实验室完成。雌性Wistar大鼠32只,体质量250～300g。切断所有大鼠右下肢的坐骨神经和股神经,然后分别制造1cm的圆形皮肤缺损作为去神经组,在大鼠左下肢相应部位制造同样皮肤缺损作为对照组,于伤后1,3,7,14d每个时间点随机处死8只大鼠,用3M贴膜覆盖于伤口,然后沿切口周围1cm切取伤口组织,观察伤口愈合情况,组织化学染色观察神经丝蛋白和降钙素基因相关肽的变化。结果:纳入大鼠32只,均进入结果分析,伤口无感染。①两组大鼠伤后7d的伤口面积比伤后1d均明显缩小[去神经组:(0.195±0.053),(0.687±0.053)cm2;对照组:(0.131±0.041),(0.562±0.088)cm2]。与对照组相比,去神经组伤后3d大鼠的伤口面积无明显变化[(0.366±0.031),(0.408±0.079)cm2,P>0.05]。②去神经组伤口的神经丝蛋白和降钙素基因相关肽阳性染色在伤后第1,3,7,14天均明显少于对照组。结论:完全去神经后皮肤伤口愈合缓慢,而伤口内的神经纤维再生缓慢和降钙素基因相关肽的减少与皮肤伤口愈合缓慢有着密切关系。     

嗅鞘细胞移植对脊髓损伤区RhoA表达的影响

目的:轴突生长抑制分子须与其共同复合受体结合后才能激活下游抑制信号RhoA,从而导致细胞骨架塌陷,抑制神经再生。基础及临床研究均证实嗅鞘细胞能够促进脊髓功能的恢复,观察嗅鞘细胞移植前后脊髓损伤区RhoA的动态变化,探讨嗅鞘细胞移植治疗脊髓损伤的可能机制。方法:实验于2005-09/2006-05在西安交大医学院环境与基因重点实验室完成。①实验动物:成年SD大鼠40只,随机数字表法分为正常组、模型组、嗅鞘细胞组、DF12对照组,10只/组。另取30只健康成年雄性SD大鼠作为嗅鞘细胞的来源。实验过程中对动物的处置符合动物伦理学标准。②实验方法:大鼠麻醉后处死,迅速取出头部两侧嗅球,除去软膜,剪取嗅球外面的嗅神经层和小球层,剪碎后离心,胰蛋白酶消化获取嗅鞘细胞悬液。除正常组外,其余各组均建立全横切脊髓损伤模型。嗅鞘细胞组将原代培养12 d的嗅鞘细胞悬液调整为1×10~(11)L~(-1),在距损伤缘上下各1 mm处分4点应用微量注射器注射,深度1.0 mm,每处各注射1μL。DF12对照组同法每点注射等量DF12培养液,模型组、正常组不进行任何处理。③实验评估:各组分别于移植后1,2,4,6,8周采用免疫组化和Western blot免疫印迹技术动态检测脊髓损伤区RhoA表达的变化。同时在移植后8周行嗜银染色检测组织形态学变化。结果:①RhoA表达的变化:正常组RhoA表达的吸光度值明显低于其余3组(P<0.05)。嗅鞘细胞组于移植后1,2,4,6,8周脊髓损伤区RhoA的表达均明显低于模型组和DF12对照组(P<0.01),而模型组和DF12对照组差异无显著性意义(P> 0.01)。②组织形态学变化:嗅鞘细胞移植8周后除正常组外,其余各组均可见明显的神经纤维再生,但模型组与DF12对照组大部分纤维排列紊乱,再生纤维方向性较差;嗅鞘细胞组可见明显的新生轴突,且神经纤维跨越损伤部位修复脊髓损伤,无论在数量还是质量上均优于模型组及DF12对照组。结论:嗅鞘细胞移植可能通过降低脊髓损伤区RhoA蛋白的表达,从而促进损伤脊髓的修复。     

脉压水平与经皮冠状动脉介入术患者的危险分层及预后评价

目的:通过对接受经皮冠状动脉介入治疗患者的临床特征,围手术期并发症和远期的疗效分析,了解脉压水平与经皮冠状动脉介入术患者的危险分层和预后关系。方法:选择2003-10/2005-10就诊于解放军第三○五医院心脏介入中心符合冠心病诊断标准并接受经皮冠状动脉介入治疗的631例患者。外周肱动脉压力测定收缩压、舒张压,脉压水平通过收缩压与舒张压差表示,冠状动脉病变的严重程度用冠脉病变积分表示。采用横断面前瞻性多变量观察研究,根据脉压>65mm Hg(1mm Hg=0.133kPa)和≤65mm Hg进行分组,其中脉压>65mm Hg组154例,男110例,女44例;脉压≤65mm Hg组477例,男288例,女189例。观察患者临床特征,随访[随访时间(18.6±4.3)个月]主要心血管事件发生率。结果:631例患者均进入结果分析。①与脉压≤65mm Hg组比较,脉压>65mmHg组年龄偏大,男性多见,高血压病史和糖尿病史多,C型病变和三支病变常见,冠脉病变积分高。②脉压>65mmHg组围手术期并发症发生率、住院期非致死性心肌梗死发生率和远期心源性死亡发生率显著高于脉压≤65mmHg组(16.8%,8.8%;5.2%,2.3%;1.3%,0.8%,P均<0.05)。③多因素logistic分析冠脉病变严重程度与脉压、年龄、糖尿病有正相关,OR分别为1.181(95%CI1.120～1.321),1.012(95%CI1.009～1.213),1.273(95%CI1.042～1.359)。结论:脉压与冠状动脉病变的严重程度密切相关,与经皮冠状动脉介入术围手术期及远期不良心血管事件发生率增加密切相关,可作为全身心血管疾病的一个危险信号,指导早期干预。     

干细胞诱导分化为胰腺β细胞的研究现状

学术背景：干细胞体外诱导分化成的胰岛细胞可以发挥对血糖的生理性调节作用。大量研究证明可以从胚胎干细胞、胰腺干细胞、骨髓间充质干细胞、神经干细胞、肝脏干细胞或脐血干细胞等诱导分化出胰腺β细胞。目的：深入认识干细胞诱导分化为胰腺β细胞的研究现状。检索策略：由该论文的研究人员应用计算机检索Pubmed数据库1990—01，2006—07的相关文献，检索词“stem cell，differenliation，culture，pancreas”，并限定文章语言种类为English。同时计算机检索维普数据库2000-01，2006—07的相关文献，检索词“干细胞，胰岛，诱导分化”，并限定文章语言种类为中文。共检索到142篇文献，对资料进行初审，纳入标准：①与干细胞和干细胞向胰腺β细胞诱导分化相关的文章。②若内容相似，选取首次实验报告及近5年较权威杂志发表的文章。排除标准：重复或类似的研究。文献评价：文献的来源主要是通过对干细胞向胰腺β细胞诱导分化方面内容进行汇总分析。所选用的30篇文献中，1篇为综述，其余均为临床或基础实验研究。资料综合：胰岛移植是目前治疗Ⅰ型糖尿病和部分Ⅱ型糖尿病效果最理想的方法。由干细胞诱导分化得到的胰腺β细胞可以发挥调节血糖的作用，在许多小鼠糖尿病模型研究中起到了降低血糖的作用。目前用于诱导分化为胰腺β细胞的干细胞来源包括胚胎干细胞、胰腺干细胞、骨髓间充质干细胞、神经干细胞、肝脏干细胞或脐血干细胞等。在不同的干细胞诱导分化为胰腺β细胞的研究中，分为体内和体外两种诱导分化方法，而体外诱导法多数采用分步诱导的方式，也有部分实验利用基因技术的方法进行诱导。结论：不同来源的干细胞可以在体外通过多种方法诱导分化得到胰腺β细胞，但得到的胰腺β细胞数量及其诱导分化方法还有待进一步研究。     

Regulation of human monocyte surface antigen expression. I. Up- modulation of Mo3e antigen expression on U-937 and HL-60 cells stimulated by pharmacologic activators of protein kinase C

Mo3e is a protein (p 50,80) that is expressed on the surface of human monocytic cells after exposure in vitro to soluble activating factors that include bacterial lipopolysaccharide, muramyl dipeptide, and phorbol myristate acetate (PMA). The surface expression of Mo3e may represent a cellular event that occurs in response to the formation of "secondary messengers" that include diacylglycerol, inositol trisphosphate, and calcium ions. This postulate is based on the stimulatory effect of agents that can mimic the activity of endogenous diacylglycerol (PMA and other biologically active phorbol compounds, mezerein, and L-alpha-1,2 dioctanoylglycerol) and inositol trisphosphate (ionomycin) on Mo3e expression by U-937 and HL-60 cells. The inhibitory effect of phospholipid-active calmodulin inhibitors (trifluoperazine, chlorpromazine, and dibucaine), calcium antagonists (nicardipine and TMB-8), and EGTA further support the involvement of phospholipid- and calcium-dependent protein kinase (protein kinase C) and calcium ions in the up-modulation of Mo3e surface expression.     

单剂量巴利昔单抗对肾移植受者外周血Foxp3mRNA、CD4+CD25+调节性T细胞、白细胞介素2及其受体的影响

目的观察单剂量巴利昔单抗对肾移植受者外周血Foxp3mRNA、CD4+CD25+调节性T细胞、白细胞介素2及可溶性白细胞介素2受体的影响,分析其预防移植肾急性排斥反应的作用途径.方法选择2005-10,2006-12在上海解放军第四五五医院行同种异体肾移植的患者66例,移植前均行维持性血液透析治疗.按随机数字表法分为2组,常规组接受常规免疫抑制剂治疗,巴利昔单抗组在常规免疫抑制剂治疗的基础上加用巴利昔单抗(商品名舒莱,诺华制药公司,批号S20040059,20 mg/瓶),每组33例.另外选择年龄性别相配的健康体检者30例作为对照组.以上所有观察对象均知情同意,且得到医院伦理道德委员会批准.两组肾移植患者分别于移植前(手术当天)和移植后1,2,4,8周清晨采静脉血肝素抗凝,以流式细胞仪检测外周血中CD4+CD25+调节性T细胞含量,应用荧光定量PCR检测Foxp3mRNA的表达,应用双抗体夹心酶联免疫吸附法检测血浆中自细胞介素2及其受体,采用生化仪检测血肌酐及尿素氮水平,必要时行移植肾多普勒超声检查和病理活检,观察其急性排斥反应发生情况.结果66患者全部进入结果分析,无脱落.①常规组患者急性排斥反应的发生率21.12%(7/33)显著高于巴利昔单抗组6.1%(2/33)(p＜0.05).②移植后第1,2,4和8周巴利昔单抗组Foxp3、CD4+CD25+调节性T细胞和白细胞介素2水平均高于常规组(P＜0.05～0.01),可溶性白细胞介素2受体水平均低于常规组[(306.31±98.43,327.60±109.74,316.71±104.54,388.33±13242;410.14+112.04,442.82±118.94,450.80±123.63,445.61±115.24)U/mL(p＜0.05～0.01)].③两组肾移植患者无论移植前还是移植后,其血浆CD4+CD25+调节性T细胞百分率与Foxp3mRNA表达水平均呈明显正相关(r=0.892～0.932,P＜0.01).结论单剂量巴利昔单抗可以有效地减少移植肾急性排斥反应的发生率,作用途径可能与其增加外周血中Foxp3mRNA、CD4+CD25+调节性T细胞和白细胞介素2表达,减少血浆可溶性白细胞介素2受体水平有关.     

去甲乌药碱衍生物及其开环类似物的合成

去甲乌药碱具有强心作用,为了寻找更有效的化合物,设计合成了一系列去甲乌药碱类似物,其中包括B环开环类似物;双-四氢异喹啉类及其开环类似物;氨基侧链取代C环等。在所合成的化合物中,D_2呈明显活性,优于去甲乌药碱。     

老年肾病综合征28例

1 临床资料 2002/2004年行肾活检的老年(≥60岁)住院肾病综合征患者28(男19,女9)例,按WHO标准进行病理学分类(表1).全部病例给予强的松每日1 mg/kg,晨顿服,8～12 wk后渐减量至最小量维持治疗.9例患者因激素反应欠佳而加用环磷酰胺治疗.完全缓解: 水肿消退,24 h尿蛋白＜300 mg;部分缓解: 水肿消退,24 h尿蛋白300～1500 mg;无效: 临床征状改善或无改善,肾功能恶化(表1,2).