Direct molecular diagnosis of myotonic dystrophy

Hecht BK, Donnelly A, Gedeon AK, Byard RW, Haan EA, Mulley JC. Direct molecular diagnosis of myotonic dystrophy. Clin Genet 1993: 43: 276–285. © Munksgaard, 1993 Myotonic dystrophy (DM) arises from an unstable trinucleotide (CTG_n) repeat sequence within the DM locus at 19q13.3. Twenty-three myotonic dystrophy families containing 205 persons with no symptoms, minimal manifestations, classic DM or congenital DM were investigated to validate the application of the pM10M6 probe to direct molecular diagnosis. Affected family members had been diagnosed clinically and the unaffected family members had been assigned carrier probabilities close to either zero or 100%, using closely linked flanking markers. Southern analysis identified all 89 DM gene carriers as having expansions of the unstable element. PstI detected all small expansions of the repeat sequence as easily seen discrete bands; but large expansions were usually seen as diffuse smears, sometimes difficult to distinguish from lane background. EcoRI concentrated these diffuse smears, associated with somatic instability, into discrete bands which were easy to detect; but it did not resolve the smaller expansions present in 9 (10%) of the DM carriers. It is essential that PstI and EcoRI gels are run in parallel to detect all DM gene carriers. The extent of expansion of CTG correlated with age of onset and disease severity. Biopsies of various fetal tissues from two terminated pregnancies confirmed the diagnosis obtained by CVS and revealed no heterogeneity between tissues at this developmental stage. Further expansion occurred during the culture of CVS cells, indicating that direct prenatal diagnosis needs to be carried out on CVS tissue rather than on cultured cells. The intergenerational change of the repeat sequence from DM parent to DM offspring showed a significant parental sex difference for those parents with large expansions. Contraction of the unstable element was observed in the three males carrying the largest expansions and could explain why congenital DM is exclusively of maternal origin.     

长骨内开口效应对其力学性能影响的理论模型研究

建立一个股骨中段的外侧皮质带有矩形开口的力学模型,采用有限元方法,计算骨开口区的尺寸改变时,股骨的扭转刚度和应力分布的变化。结果表明:骨开口长度为骨外径的1倍时(1OD),对股骨扭转刚度和剪应力分布的影响较小;开口长度从2OD增至4OD时扭转刚度急剧减小,而且剪应力的最大值位于开口区中心。本结论对临床骨科的手术治疗方法和骨开口尺寸的控制提供了重要的理论依据。     

椎间盘部分切除对腰椎应力分布影响的有限元分析

腰椎间盘突出症是骨科常见病之一。椎间盘切除术被广泛应用于本症的治疗。本文采用有限元素分析法观察了椎间盘部分切除前后腰椎应力分布的改变。本研究观察到,在正常情况下,椎体上下缘的中央部位承受较大的应力;椎间盘部分切除术后,椎体上下缘的侧方承采应力大于中央部分。这些结果表明,椎间盘部分切除术后可引起腰椎应力分布紊乱,出现应力集中,引起骨质增生,从而影响手术的远期疗效。     

Integration from proteins to organs: the IUPS Physiome Project

The IUPS Physiome Project is an internationally collaborative open source project intended to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales and across all organ systems. Here, we illustrate the application of this multi-scale modeling approach to three organ systems: the heart, the lungs and the musculo-skeletal system, and in each case we show how the organ level models incorporate tissue and cell-level physiology. Although the computational physiology framework presented here does not yet incorporate models of ageing processes, the model-based approach is certainly capable of describing ageing and disease-related processes both via parameter changes within the models of normal physiological processes and via models of additional processes added to the framework.     

基于冷冻切片的人体腰椎三维有限元模型

目的利用上海交通大学生命质量与机械工程研究所自主开发的冷冻切片处理软件CryoSegmemation提取人体骨骼的边缘,利用逆向工程软件Imageware建立骨骼的面模型,在ANSYS中建立人体腰椎的三维有限元模型。方法利用第三军医大学的第一例男性冷冻切片数据进行图像处理,截面轮廓线信息处理。结果准确快速地建立了完全符合人体解剖特征的腰椎三维有限元模型。结论利用该研究所自主开发的冷冻切片软件和一些现有的商用软件可以准确、快速地建立人体腰椎的三维面模型、体模型及有限元模型,为航空、车辆、船舶、生物医学工程等不同的领域进行数值模拟计算和动力学仿真提供完全符合人体解剖学特征的原始模型。     

冠状动脉支架抗压缩性能的有限元分析

冠状动脉支架作为经皮穿刺冠状动脉成形术中保持病变血管畅通的核心器件。其对病变动脉壁的支撑作用如何是支架植入术成功的先决条件之一。依据冠脉支架抗压缩性能的实际测试原型，建立起对应的有限元模型，并利用此方法系统地研究了专利支架设计，其扩张尺度的不同和筋的尺寸变化对支架抵抗两平面压缩性能的影响。结果显示，随支架扩张直径的增大，其抵抗两平面压缩的作用减小，增加支架筋的宽度或厚度能够提高支架的抗压缩性能，且这两个方向尺寸的增加对提高抗压缩性能的作用相当。模拟与实验结果一致，表明有限元模拟可以在一定程度上替代支架原型测试工作。     

Program for generation of three-dimensional finite element mesh from magnetic resonance imaging scans of human limbs

A PC-AT based program for conversion of magnetic resonance imaging (MRI) scans into coordinate input for finite element mesh generation is presented. The program is written in Borland C + +3.1 and is compatible with every general-use personal computer, permitting the use of MS-DOS 3.0 or higher with a Microsoft mouse. The program is menu driven and does not demand specialised knowledge from the user. The system and memory requirements are minimal -- 640 kB RAM -- and it runs as a stand-alone program. A second program allows the construction of a three-dimensional representation of the limb sub-structure and generation of the FE mesh from the converted cross-sectional scans. The capabilities of the program are demonstrated using cross-sectional scans of the upper arm; the fat, muscle and bone contours were obtained to a very high level of precision (0.4 mm).     

肝癌特异性超抗原SEA(D227A)基因表达载体的构建与表达

目的：构建受AFP顺式作用元件调控的超抗原表达载体，将SEA(D227A)特异性的表达于AFP阳性肝癌细胞膜表面。方法：PCR扩增AFP基因启动子、增强子、linker—CD80tm和SEA(D227A)。将上述片断插入逆转录病毒载体pLXSN的多克隆位点，构建AFP基因顺式作用元件调控的肝癌特异性减毒超抗原表达载体(pLXSN SEA(D227A)—linker—CD80tm)。通过脂质体介导，以表达载体转染表达或不表达AFP的肿瘤细胞系，用RT—PCR和间接免疫荧光染色，检测SEA的表达。结果：成功地将AFP基因的启动子、增强子、linker—CD80tm和SEA(D227A)克隆到逆转录病毒载体pLXSN的多克隆位点，酶切鉴定和DNA序列分析无误，RT—PCR和间接免疫荧光法检测证实，SEA(D227A)能在AFP阳性的肝癌细胞膜特异性表达。结论：AFP顺式作用元件修饰的超抗原表达载体的构建，为下一步用其强化肝癌的免疫治疗奠定了基础。     

腹主动脉瘤应力模型的建立及其应用

本研究用螺旋CT扫描腹主动脉瘤获得的断层图像合成腹主动脉瘤几何模型，通过设定瘤壁组织生物力学参数和边界条件，使用有限元分析的方法分析腹主动脉瘤瘤壁的应力分布。结果标明，本例腹主动脉瘤应力峰值位于远端分叉部位，瘤体应力峰值位于后壁，均小于瘤壁的承受极限。本研究所得结果对腹主动脉瘤应力模型有助于分析个体化腹主动脉瘤的破裂部位和生长方向，对研究疾病进程提供依据。