美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

The Morbidity of Multiple Sclerosis

Although the clinical course of multiple sclerosis is benignin up to one-third of patients, it is important to recognizethe high rate of morbidity in others. Most individuals passthrough a remitting phase but in a significant proportion theclinical manifestations subsequently recur, persist or slowlyprogress, and disability accumulates with time. Here we describethe frequency and spectrum of morbidity in a population basedcohort of patients with multiple sclerosis. These statisticswill guide those providing health care resources and planningservices for patients with multiple sclerosis.     

胰岛素生长因子对骨髓基质细胞增殖和向成骨细胞分化的调节

目的:观察胰岛素生长因子对骨髓基质细胞向成骨细胞分化的调节作用。方法:实验于2005-11/2006-04在广东医学院附院中心实验室进行。①实验材料:重组胰岛素生长因子(GIBCO),DEME培养基(GIBCO),胰蛋白酶(GIBCO),胎牛血清(杭州四季青),二甲基亚砜(sigma),四甲基偶氮噻唑盐(sigma),碱性磷酸酶试剂盒(长城临床试剂公司),骨钙素试剂盒(天津九鼎)。SD大鼠由广东医学院动物部提供。②实验方法:骨髓基质细胞的分离:将SD大鼠处死后,无菌条件下取出动物的双侧股骨和胫骨,分离培养骨髓基质细胞。骨髓基质细胞成骨诱导条件:取第2代骨髓基质细胞,用含体积分数为0.1胎牛血清、50mg/L维生素C、10mmol/Lβ-甘油磷酸钠、10-8mol/L地塞米松、100U/mL青霉素、100U/mL链霉素成骨诱导培养液培养,置37℃、体积分数为0.05CO2饱和湿度培养箱内孵育。倒置显微镜观察细胞生长状况。③实验分组:将第3代骨髓基质细胞随机分为对照组和实验组。细胞增殖实验:取第3代生长良好的骨髓基质细胞,密度调整至4×106L-1。实验组加入含1,10,20μg/L胰岛素生长因子诱导培养液,对照组加不含胰岛素生长因子诱导培养液。培养1,3,5,7d后采用MTT法检测细胞增殖水平。用碱性磷酸酶试剂盒在全自动生化分析仪上测定细胞内碱性磷酸酶活性。④实验评估:采用RI测定上清液中骨钙素含量。观察胰岛素生长因子对骨髓基质细胞增殖和向成骨细胞方向分化的调节作用。结果:①MTT法测骨髓基质细胞增殖情况:与对照组相比,实验组具有明显促进骨髓基质细胞增殖作用(吸光度值:1d,0.442±0.002,0.498±0.009,0.546±0.004,0.553±0.005;3d,0.571±0.008,0.604±0.007,0.682±0.006,0.694±0.009;5d,0.623±0.003,0.659±0.004,0.793±0.008,0.807±0.007;7d,0.792±0.008,0.810±0.006,0.912±0.003,0.923±0.004,P<0.05)。20μg/L胰岛素生长因子与10μg/L胰岛素生长因子组的作用效果差异无显著性意义(P>0.05)。实验组随时间延长,对骨髓基质细胞均有明显促进作用。②骨髓基质细胞内碱性磷酸酶、骨钙素合成的变化:实验组细胞胞浆内碱性磷酸酶明显高于对照组,差异有显著性意义(t=3.08,P<0.05)。实验组细胞胞浆内骨钙素明显升高,是对照组的1.8倍,差异有显著性意义(t=2.82,P<0.05)。结论:适当质量浓度胰岛素生长因子能促进经诱导分化骨髓基质细胞的增殖和向成骨细胞方向的分化。     

Self recognition in allogeneic radiation bone marrow chimeras. A radiation- resistant host element dictates the self specificity and immune response gene phenotype of T-helper cells

The specificity of the self-recognition repertoire in fully allogeneic (A {arrow} B), semiallogeneic (A {arrow} A x B and A x B {arrow} A), and double donor (A + B {arrow} A) radiation bone marrow chimeras was assessed by the ability of their spleen cells to generate in vitro primary plaque-forming cell (PFC) responses to trinitrophenyl- keyhole limpet hemocyanin. In contrast to spleen cells from semiallogeneic and double donor chimeras, intact spleen cells from fully allogeneic BI0 {arrow} B10.A and B10.A {arrow} B10 chimeras were not capable of generating responses to trinitrophenyl (TNP)-keyhole limpet hemocyanin. However, cultures containing a mixture of both B10 {arrow} B10.A and B10.A {arrow} B10 spleen cells did respond, demonstrating that all the cell populations required for the in vitro generation of T-dependent PFC responses were able to differentiate into functional competence in a fully allogeneic major histocompatibility complex (MHC) environment. The self recognition repertoire of T-helper cells from fully allogeneic A {arrow} B chimeras was determined to be specific for the recognition of host, not donor, MHC determinants in that they were able to collaborate with cells expressing only host MHC determinants but not with cells expressing only donor MHC determinants, even though the functional lymphocytes in these chimeras were shown to be of donor origin. Experiments utilizing double donor A + B {arrow} A chimeras further demonstrated that the ability of chimeric T cells to recognize allogeneic MHC determinants as self structures was a function of a radiation-resistant host element and not simply a consequence of the tolerization of T cell precursors to allogeneic MHC determinants, because strain A lymphocytes isolated from A + B {arrow} A chimeras were tolerant to both A and B MHC determinants but were restricted to the self recognition of syngeneic host type A MHC determinants. Finally, the Ir gene phenotype expressed by B10 {arrow} B10.A and B10.A {arrow} B10 chimeric lymphocytes was determined by their ability to function in the Ir gene controlled response to TNP-poly-L-(Tyr,Glu)-poly-D,L-Ala-poly- L-Lys [(T,G)-A--L]. The ability of lymphocytes to function in TNP-(T,G)-A--L responses was not determined by their genotype but rather paralleled the specificity of their self recognition repertoire for high responder (H-2 (b)) determinants. The possible degeneracy of the MHC-specific self recognition repertoire is discussed, and a model is proposed for Ir gene regulation in which expression of Ir gene function by lymphocytes is an antigen-nonspecific consequence of the specificity and cross-reactivity of their self recognition repertoire.     

自体移植静脉内皮细胞的缺血安全时限

目的:观察离体后不同缺血时间自体移植静脉内皮细胞的损伤程度,分析移植静脉内皮细胞缺血的安全时限。方法:实验于2005-07/2005-12在中国人民解放军胸心外科研究所完成。选择健康成年家犬29只,购自解放军第二军医大学实验动物中心。①不同缺血时间移植静脉内皮细胞损伤实验:按随机数字表法选取5只家犬,取双侧股静脉,按离体后0min,30min,60min,90min4个时间点行扫描电镜及透射电镜检查,观察内皮细胞的损伤程度,Ⅰ级正常,Ⅱ级轻度,Ⅲ级中度,Ⅳ级重度,Ⅴ级坏死,将Ⅰ,Ⅱ,Ⅲ级损伤归类为可逆性损伤;将Ⅳ,Ⅴ级损伤归类为不可逆损伤。②自体移植静脉内皮细胞缺血安全时限实验:将剩余24只家犬建立犬股静脉离体不同时间(30min,60min,90min)的自体移植模型,在术后1d,3d,7d,14d再次手术取出静脉,行扫描电镜检查,比较不同时间点移植静脉内皮覆盖率。结果:①缺血0min,30min,60min,90min组(n=60)不可逆性损伤内皮细胞数分别为12,6,28,33,缺血60min、90min组内皮细胞的损伤程度明显重于缺血0min和30min组。各组的内皮细胞覆盖率比较差异无显著性意义(P>0.05)。②24只模型犬全部存活,切口愈合佳,无红肿、溢脓或裂开。③移植术后1d,14d,缺血30min,60min及90min组内皮细胞覆盖率差异无显著性意义(P>0.05),而术后3d,7d,缺血30min组的内皮细胞覆盖率显著高于缺血60min及90min组[(62.21±3.52)%,(40.09±2.56)%,(36.17±4.55)%(P<0.01);(82.31±3.76)%,(60.22±3.23)%,(59.39±4.27)%(P<0.01)]。结论:缺血60min后静脉内皮细胞的超微结构会发生明显的不可逆性损害,移植静脉内皮细胞缺血的安全时限是60min。     

Interfacing the ICU with the general practitioner

For many reasons it is crucial that treating intensivists have (regular) contact with general practitioners (GPs). Information about the premorbid condition of the patient, their will and wishes, is of importance to be able to set appropriate treatment goals. The GP is the doctor who is responsible for the patient once discharged from the hospital. Additionally, the GP can play an important early role in the support of relatives, provided the GP is timely informed. This kind of communication should be organized in a structured way within the intensive care unit department.