CFTR 5T variant has a low penetrance in females that is partially attributable to its haplotype.

PURPOSE: The study's purpose was to understand the molecular basis for different clinical phenotypes of the 5T variant, a tract of 5 thymidines in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which disrupts processing of CFTR mRNA and reduces synthesis from the corresponding CFTR alleles. METHOD: We analyzed the polymorphic TG dinucleotide repeat adjacent to the 5T variant in intron 8 and the codon 470 in exon 10. Patients selected for this study were positive for both the 5T variant and the major cystic fibrosis mutation, Delta F508. Almost all Delta F508 mutation alleles occur in a 10TG-9T-470M haplotype. Therefore, it is possible to determine the haplotype of the 5T variant in trans. RESULTS: Of the 74 samples analyzed, 41 (55%) were 11TG-5T-470M, 31 (42%) were 12TG-5T-470V, and 2 (3%) were 13TG-5T-470M. Of the 49 cases for which we had clinical information, 17.6% of females (6/34) and 66.7% of males (10/15) showed symptoms resembling atypical cystic fibrosis. The haplotype with the highest penetrance in females (42% or 5/12) and more than 80% (5/6) in males is 12TG-5T-470V. We also evaluated 12 males affected with congenital bilateral absence of vas deferens and positive for the 5T variant; 10 of 12 had the 12TG-5T-470V haplotype. CONCLUSION: Overall, the 5T variant has a milder clinical consequence than previously estimated in females. The clinical presentations of the 5T variant are associated with the 5T-12TG-470M haplotype.     

Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography

The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [¹⁴C]clorgyline in normal, conscious rat brain. [¹⁴C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [¹⁴C]methyliodide. Sixty minutes after [¹⁴C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.     

基于暗视场荧光图像分析的大鼠微血管流速测量系统的建立

将荧光标记的自身红细胞注入SD大鼠体内,在荧光显微镜下观测标记红细胞在大鼠微血管中的流动情况,并通过显微摄像系统将整个过程以视频信号的形式存贮。使用视频采集卡将流速变化过程回放采样,得到暗视场下的荧光图像。然后利用帧图像分离出奇偶场的图像分析方法测定血流速度。在该系统下测量流动小室中荧光小球的流速,得到的测量值与实际值之间的误差小于7%,两者没明显的差异(P>0.05),流速测量的上限为9.6mm/s。并在大鼠微循环障碍研究中,应用此系统得到了血流速度随时间变化的情况。     

不同运动强度对骨质疏松影响的数值模拟

探讨数值模拟不同运动强度对因废用引起的骨质疏松的影响。依据骨的功能适应性和力学调控系统理论,遵循骨重建的生理过程,建立了一个带有时间历程的描述松质骨骨质疏松过程的计算模型,用C语言编制程序。得到了不同运动负荷对因废用引起的骨质疏松(孔隙率)的影响曲线。结果表明:较大的运动强度可以减缓因废用引起的骨质疏松。这对于运动防治骨质疏松有一定的参考价值。     

北京市三所高校大学生SARS流行期的心理状态现况调查

目的 :了解SARS流行时期大学生在封闭式管理下的心理状况。方法 :采用症状自评量表、ZUNG氏焦虑自评量表、ZUNG氏抑郁自评量表和一般状况调查表 ,以分层整群抽样的方法 ,对北京市三所重点大学 62 80名在校本科大学生和研究生进行了心理状况自评问卷调查。结果 :症状自评量表的因子阳性检出率为 7 3 % ,各因子得分均明显低于既往北京市大学生调查结果 ;除恐怖因子和精神病性因子外 ,各因子得分均低于或接近国内常模 (t=2 17-5 3 65 ,P <0 0 5 )。焦虑症状阳性检出率为 9 5 % ,抑郁症状阳性检出率为 2 9 6%。结论 :北京市SARS流行期间大学生存在焦虑、抑郁症状 ;采取了有效的传染病防治和健康教育等措施后大学生群体的心理健康状况良好。     

Structure and evolution of the Smith-Magenis syndrome repeat gene clusters, SMS-REPs

An approximately 4-Mb genomic segment on chromosome 17p11.2, commonly deleted in patients with the Smith-Magenis syndrome (SMS) and duplicated in patients with dup(17)(p11.2p11.2) syndrome, is flanked by large, complex low-copy repeats (LCRs), termed proximal and distal SMS-REP. A third copy, the middle SMS-REP, is located between them. SMS-REPs are believed to mediate nonallelic homologous recombination, resulting in both SMS deletions and reciprocal duplications. To delineate the genomic structure and evolutionary origin of SMS-REPs, we constructed a bacterial artificial chromosome/P1 artificial chromosome contig spanning the entire SMS region, including the SMS-REPs, determined its genomic sequence, and used fluorescence in situ hybridization to study the evolution of SMS-REP in several primate species. Our analysis shows that both the proximal SMS-REP (approximately 256 kb) and the distal copy (approximately 176 kb) are located in the same orientation and derived from a progenitor copy, whereas the middle SMS-REP (approximately 241 kb) is inverted and appears to have been derived from the proximal copy. The SMS-REP LCRs are highly homologous (>98%) and contain at least 14 genes/pseudogenes each. SMS-REPs are not present in mice and were duplicated after the divergence of New World monkeys from pre-monkeys approximately 40-65 million years ago. Our findings potentially explain why the vast majority of SMS deletions and dup(17)(p11.2p11.2) occur at proximal and distal SMS-REPs and further support previous observations that higher-order genomic architecture involving LCRs arose recently during primate speciation and may predispose the human genome to both meiotic and mitotic rearrangements.     

家庭社会经济状况与3岁以内儿童生长发育及营养状况的关系

目的 探究家庭社会经济状况(SES)与3岁以内儿童生长发育及营养状况的关系,为我国儿童预防保健提供科学依据。方法 数据源于2015年中国九市7岁以下儿童体格发育调查的西安地区数据。研究共纳入父/母亲文化程度、父/母亲职业和家庭年收入5项指标因子,构建了SES综合指标作为自变量。结局变量为身长、体重和评估的营养状况结局。调整儿童性别和月龄后,分别建立线性回归和Logistic回归模型,分析SES与身长体重和营养结局的关系。结果 研究共纳入3岁以内儿童12 017人,经评估营养不良者281人(2.3%),营养过剩者531人(4.4%)。调整儿童性别和月龄后,与低水平SES儿童相比,中等水平SES儿童身长增加0.32 cm(95%CI:0.16~0.47),发生营养过剩的风险降低20%(OR =0.80, 95%CI:0.65~0.98);高水平儿童身长增加0.77 cm(95%CI:0.61~0.92),体重增加0.06 kg(95%CI:0.006~0.12),发生营养过剩的风险降低33%(OR=0.67, 95%CI:0.53~0.83)。结论 较好的社会经济状况可能降低营养过剩的风险,有助于儿童的发育与营养健康。应改善家庭育儿环境,加强对低SES家庭的儿保宣教,提高儿童的健康水平。     

成人游戏力与3~8岁儿童脑功能发展的关系

3~8岁是儿童脑功能发育的重要时期,该阶段儿童大脑及其功能具有较强可塑性,而早期经验的剥夺会导致中枢神经系统发育停滞,甚至萎缩并构成永久性损害。儿童早期经验的获得大部分来自游戏,而游戏的开展离不开成年人的参与,越来越多的研究揭示了游戏力对脑功能的重要作用。本文旨在综述成人游戏力对儿童脑功能发育,如在感觉和动作、注意力和意识、学习和记忆中的作用。本综述还简述了游戏类型对脑功能的影响及现有的挑战,以期从父母、教师等成人参与游戏的角度来促进儿童脑功能健康发展。     

全反式维甲酸对培养的大鼠动脉平滑肌细胞迁移的影响

目的 :研究全反式维甲酸 (ATRA)对培养的大鼠动脉平滑肌细胞 (VSMCs)迁移的影响。方法 :血管平滑肌细胞采用组织贴块法培养 ,ATRA(2 .5× 10 -6mol/L)分别作用经PDGF -BB(2 0ng/ml)和 10 0 %FCS趋化作用下的VSMCs,采用改良的Boydenchamber方法检测VSMCs的迁移活性。结果 :ATRA作用的VSMCs对PDGF -BB和 10 0 %FCS的化学趋化活性明显减弱。结论 :ATRA具有抑制VSMCs迁移的作用。