脊髓全横断大鼠神经生长因子和脑源性神经营养因子表达及三七皂苷的干预效应

目的:神经生长因子和脑源性神经营养因子同属神经营养素家族,在神经系统发育及维持正常神经元功能中有重要作用。实验拟证实脊髓全横断损伤三七皂苷对大鼠神经生长因子及脑源性神经营养因子蛋白水平的表达变化产生了影响。方法:实验于2005-06/09在昆明医学院神经科学研究所完成。①实验材料:清洁级健康雌性SD大鼠72只,质量(200±20)g;三七皂苷由云南植物药业提供。②分组及实验过程:大鼠被随机分为4组:假手术组、单纯脊髓全横断损伤组、脊髓全横断损伤 生理盐水(0.5mL/次)组、脊髓全横断损伤 三七皂苷(100mg/kg/次)组,每组18只。于T10水平横断大鼠脊髓,假手术组仅剪开硬脊膜而不损伤脊髓。后2组于术后30min,4,24,48,72h腹腔注射给药各1次。③实验评估:各组于术后3,7及21d分别取6只大鼠L1～2段脊髓制作冰冻切片,采用免疫组织化学ABC法染色。观察并计数脊髓腹角神经生长因子、脑源性神经营养因子蛋白的表达变化;常规苏木精伊红染色观察脊髓的组织病理变化。结果:72只大鼠全部进入结果分析:①脊髓全横断损伤后脊髓出现明显的神经变性坏死、炎性浸润等病理变化,三七皂苷可减轻这些变化。②神经生长因子蛋白主要分布于灰质神经元胞浆及胶质细胞胞核中。在正常脊髓有少量表达,脊髓损伤后7d表达明显升高,直到伤后21d仍高于假手术组(P<0.05);三七皂苷可明显促进其表达,伤后3,7d均明显高于其他各组(P<0.05),在21d时下降但仍高于假手术组(P<0.05)。③脑源性神经营养因子蛋白主要分布于腹角的运动神经元胞浆中,胶质细胞未见着色。在正常脊髓有少量表达,脊髓损伤后7d表达明显升高(P<0.05),伤后21d已下降,同假手术组相比差异无显著性(P>0.05);三七皂苷可明显促进其表达,伤后3,7,21d均明显高于所有对照组(P<0.05)。结论:三七皂苷可减轻脊髓横断性损伤后继发损害,增加神经生长因子、脑源性神经营养因子表达量及提前神经生长因子、脑源性神经营养因子表达时间,提示其可以促进脊髓损伤早期修复。     

Age effects on atrophy rates of entorhinal cortex and hippocampus

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

Comparison of methods for measuring longitudinal brain change in cognitive impairment and dementia

PURPOSE: The goal of this project was to compare MRI measures of hippocampal, entorhinal cortex (ERC), and whole brain longitudinal change in cognitively normal elderly controls (C), non-demented subjects with cognitive impairment (CI), and demented (D) subjects. METHODS: 16 C, 6 CI, and 7 D subjects of comparable age were studied with MRI twice, at least 1 year apart. Longitudinal change in total brain size was measured by several methods, including computerized segmentation, non-linear warping, and change in the fluid/tissue boundaries between cerebrospinal fluid (CSF) and brain. Change in hippocampal volume was measured by semi-automated methods, and ERC volumes were manually measured. RESULTS: The annual rate of atrophy was greater in D versus C and D versus CI for cortical gray matter (cGM) (P=0.009 and 0.002), hippocampus (P=0.0001 and 0.002), and for the change in the fluid/tissue boundary (P=0.03 and 0.03). The annual rate of atrophy of ERC was greater in both CI and D versus C (P=0.01 and 0.0002). No significant differences between groups were found using non-linear warping. CONCLUSIONS: In CI, the greatest annual rates of atrophy were in ERC, while in D the greatest annual rates of atrophy were in hippocampus and cortex. Progressive ERC atrophy was observed with a greater degree of cognitive impairment, while hippocampal and cortical atrophy were only observed in demented subjects.     

第四跖背动脉逆行岛状皮瓣在第二足趾再造手指供区趾蹼皮肤缺损中的临床应用

目的探讨第四跖背动脉逆行岛状皮瓣修复第二足趾再造手指后供区趾蹼皮肤缺损的临床应用效果。方法2007年1月~2009年12月,均为切取第二足趾再造手指时携带面积不等的跖背皮瓣13例患者的临床资料进行分析。结果术后13例转移皮瓣全部存活,术后随访时间为3~16个月,皮瓣质地、感觉良好,趾蹼外形满意,供足行走功能满意。结论最大限度地保护了供足的功能,减少了植皮后并发症,是较为理想的手术方式。     

急性淋巴细胞白血病最新治疗策略(下)

4分子治疗分析肿瘤细胞中的分子遗传性变异及后天变异的方法正在快速成熟起来。这些方法通常涉及基因组学、转录特征性识别及蛋白质组学,有利于更深入地了解ALL的发病机理,使用于临床评估的靶向治疗全面发展。最终,这些层出不穷的新技术将营造出一个全新的个性化分子医学时代,创造出效果更好而毒性更低的治疗方案。尽管治疗方案均显示了药物介入控制细胞周期进程、基因转录、细胞运动、凋亡及细胞代谢信号通路的可行性(图1),但针对ALL的分子治疗情况(表1)仍差强人意。我们将从众多正处于临床前期或早期临床研究的分子治疗方案中,选择出那…     

Single-chain Fv fragment lacks carrier specificity of the native antibody

A single-chain antibody fragment (scFv) was constructed from a hybridoma antibody that binds to phosphorylcholine (PC) only when this hapten is presented in the form of the immunizing antigen (derived from Trichinella) but not when it is presented on other carriers (as found, for example, in pneumococcal capsules). The scFv derivative was found to lack this carrier specificity as it bound indiscriminately, but specifically, to the various PC-associated antigens, and exhibits a two-fold lower affinity (3.5x10(5)M(-1)) for nitrophenyl-PC than the native antibody. The findings suggest that the scFv combining site is different in fine structure from that of the native antibody.     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.