The developmental genetics of Hirschsprung's disease

Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). It displays an incidence of 1 in 5000 live births with a 4:1 male to female sex ratio. Clinical signs include severe constipation and distended bowel due to a non‐motile colon. If left untreated, aganglionic megacolon is lethal. This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells. These progenitor cells are derived from a transient stem cell population called neural crest cells (NCC). The genetics of HSCR is complex and can involve mutations in multiple genes. However, it is estimated that mutations in known genes account for less than half of the cases of HSCR observed clinically. The male sex bias is currently unexplained. The objective of this review is to provide an overview of the pathophysiology and genetics of HSCR, within the context of our current knowledge of NCC development, sex chromosome genetics and laboratory models.     

Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow

Clinical studies are evaluating possible advantages of allogeneic peripheral blood stem cell transplantation (PBSCT) over bone marrow transplantation (BMT). We compared immune reconstitution after PBSCT (n = 20) and BMT (n = 20) in terms of lymphocyte subset counts and proliferative in vitro responses to mitogens and recall antigens (follow-up: 5 to 11 months posttransplant). Additionally, 10 PBSC harvests and 10 marrow harvests were analyzed for their composition of immunocompetent cells. Compared with BMT patients, PBSCT recipients had PB counts of naive (CD4+CD45RA+) and memory (CD4+CD45RO+) helper T cells and of B cells (CD19+) that were elevated (P < .003, P < .001, and P < .004, respectively) and proliferative responses to phytohemagglutinin (P < .0001), pokeweed mitogen (P < .02), Tetanus toxoid (P < .0005), and Candida (P < .004) that were increased. PBSCT recipients received a mean of 188 (range, 44 to 280) x 10(6) naive helper T cells and 169 (range, 18 to 296) x 10(5) memory helper T cells per kilogram; the corresponding numbers for BMT recipients were 11 (range, 4 to 24) and 10 (range, 1 to 22) x 10(5) cells per kilogram, respectively. The question of whether the documented improved in vitro immune competence after PBSCT is associated with a lower incidence of infectious complications in vivo still needs further study.     

雄激素受体基因第一外显子区CAG缺失的构建及其在HEK293细胞中的表达

目的：构建雄激素受体基因第一外显子区CAG重复序列缺失的突变重组体，观察CAG重复序列的有，无对雄激素受体转录及表达的调控作用。方法：实验于2006—05／2007—05在解放军总医院老年医学研究所完成。按照重叠延伸反应的原理扩增CAG重复序列两端的基因片段，再将两片段混合，在加入一个引物的情况下进行8个PCR循环以有效完成重叠延伸，然后再加入另一引物进行22个循环，完成目的片段指数扩增，将目的片段克隆至真核表达载体PAR-IRES2-EGFP，转染HEK293细胞，采用Western blot法检测HEK293细胞雄激素受体蛋白。结果：构建的CAG重复序列缺失的突变重组体经酶切鉴定和DNA测序证实构建正确，转染真核细胞可检测到雄激素受体基因的表达。结论：重叠延伸PCR是进行体外基因拼接、体外缺失突变的简单、快速的基因重组技术；雄激素受体基因第一外显子区CAG重复序列缺失的突变重组体的成功构建可为今后的相关研究提供实验基础。     

大连理工大学图书馆员的人格因素和职业现状分析

目的:通过对图书馆员的人格因素和职业现状分析,为图书馆的人力资源管理提供参数。方法:于2005-06/08纳入大连理工大学伯川图书馆馆员72人作为人格测试组,男7人,女65人;同时纳入2005-07前在职的全部馆员122人作为职业现状分析组,男26人,女96人。采用国际公认的卡特尔16种人格因素问卷,对人格测试组进行人格测试。问卷从16个相对独立的人格维度对人进行描绘,全套测试题共187题,每题设有a,b,c3种可供选择的答案。将测试结果输入心理测试软件系统,给出粗分和标准分,再运用软件进行数据的统计分析。对职业现状分析组的全体馆员进行了性别,年龄结构,男女馆员在各工作部门的分布,及馆员的学历构成,技术职称和领导职务的担任比例统计分析。观察人格测试组卡特尔16种人格因素问卷人格类型的次元因素和综合个性应用评价分数,并对全体馆员的自然状况列表进行统计分析,分析其职业现状。结果:发放卡特尔16种人格因素问卷72份,回收完整问卷46份,回收率63.9%,有效率100%。最终人格测试组46人进入结果分析,男5人,女41人。职业现状分析组122人,全部进入结果分析。①人格测试组聪慧性、幻想性、自律性均高于全国专业技术人员常模,差异有显著性意义(9.74±1.22;8.88±1.22;13.11±2.36,11.83±1.25;13.89±2.59,12.40±1.47;t=4.780,3.676,3.901,2.783,P<0.001～0.01)。被试馆员怀疑性和紧张性低于全国专业技术人员常模,差异有显著性意义(9.39±2.85,10.56±1.57;9.76±3.72,11.19±1.65;t=-2.783,-2.606,P<0.01,0.05)。②女性图书馆员占总人数的78.7%,男性图书馆员在年龄结构上处于年龄段的两端,在生理上处于成年早期(30.7%)和晚期(38.4%);女性馆员的年龄集中于30～50岁的年龄段(86.3%)。③男馆员在综合办公室、自动化部和技术服务部的人数分布方面占据优势地位(38.4%,11.5%,11.5%);而女性馆员集中于期刊咨询部、文献建设部、流通阅览部和回溯建库等信息服务咨询部门(24%,15.6%,40.6%,4.2%)。④男馆员在获得博士、双学士、学士学位,及本科、中专学历方面的人数比例大于女性馆员,而女性馆员在获得硕士学位及大专和较低学历方面所占的比例大于男性馆员。⑤男性馆员在高级技术职称和馆级领导高端决策层占优势,在初级和较低技术职称中占比例较大;女性馆员在中级技术职称中级领导层上占比例大于男性馆员。结论:图书馆员女性化,而男性馆员在知识结构、职称、高端决策层领导职务的担任和承担高技术性工作方面的整体水平优于女性馆员。更应着重分析女性图书馆员的生理、心理特点,人格因素和职业特征,进行人力资源的优化组合。