家族性肥厚型心肌病一家系的调查分析

目的:分析一家族性肥厚型心肌病的特点。方法:对我院就诊的一肥厚型心肌病大家系进行临床调查研究,分析其临床特点,绘制家系图谱。结果:该家系为连续四代遗传,家系成员共35例,患者11例,猝死3例,死亡2例。有1例患者房颤及脑梗塞,2例患者行永久性起搏器植入术,猝死年龄最小3岁,符合肥厚型心肌病高发病率、高猝死率、发病年龄早等特点。结论:家族性肥厚型心肌病详细的家系调查有助于了解疾病全貌,更好地揭示其遗传规律。     

Electrocutaneous Sensitivity: Effects of Skin Temperature

The effect of human skin temperature on electrocutaneous sensitivity was examined using brief capacitive discharges. Stimuli were designed to ensure that sensory effects would be independent of skin resistance and would reflect underlying neural excitability as closely as possible. Skin temperature was manipulated by immersing the forearm in circulating hot or cold air. Detection thresholds on the arm and fingertip were raised by cooling, but were not altered by heating. Temperature-related sensitivity shifts were described by the same multiplicative factors for both threshold and suprathreshold levels. The temperature coefficient (Q₁₀) for cutaneous sensitivity under these conditions was approximately 1.3.     

The Distribution of Afferent Neurons in the Trigeminal Mesencephalic Nucleus and the Central Projection of Afferent Fibers of the Mylohyoid Nerve in the Rat

Horseradish peroxidase conjugated to wheatgerm agglutinin (HRP:WGA) was injected into the proximal cut ends of three branches of the mylohyoid nerve in rats: the branch to the mylohyoid muscle (BrMh), the branch to the anterior belly of the digastricus muscle (BrDg), and the cutaneous branch (BrCu). HRP-labeled cells were detected in the ipsilateral caudal portion of the trigeminal mesencephalic nucleus (Vmes) and the ipsilateral ventromedial division of the trigeminal motor nucleus, except when HRP:WGA was applied to the BrCu. Morphologically, all labeled Vmes cells were of the pseudounipolar type.

Projections of the primary afferents of the BrMh were observed in the ipsilateral trigeminal nucleus caudalis, the upper cervical dorsal horns of laminae I -III, and the dorsolateral recticular formation (Rf), whereas the primary afferents of the BrDg terminated in the ipsilateral trigeminal nucleus principalis and Rf. These observations suggest that the role of the afferent inputs of the mylohyoid muscle differs from that of those of the anterior belly of the digastricus muscle in terms of several functions associated with jaw-closing and infrahyoid muscles.     

胃底腺息肉的研究进展

胃底腺息肉是指胃底胃体粘膜形成的多发性广基息肉样隆起,为胃体腺上皮的增生。国内外研究均证明本病高发于40-60岁女性,年龄及性别差异显著。过去认为本病的发生与家族性腺瘤性息肉病密切相关,但近年来人们认为无家族性腺瘤性息肉病的人群也可以发生胃底腺息肉。国内外学者们研究了家族性腺瘤性息肉病、Helicobacter pylori感染、质子泵抑制剂的应用、β-连环蛋白基因变异、胆汁反流等与本病发生的相关性,有学者认为Hp感染与疾病发生成负相关,质子泵抑制剂的长期应用会导致疾病的发生,β-catenin基因突变影响了APC/β-catenin途径,从而导致胃底腺息肉的产生。目前对于疾病发生的相关危险因素及发病机制,国内外仍无定论。本文将近年来中外学者的研究加以总结并提出进一步设想。     

Defective neurite extension is caused by a mutation in amyloid β/A4 (Aβ) protein precursor found in Familial Alzheimer's Disease

Clonal central nervous system neuronal cells, B103, do not synthesize detectable endogenous APP or APLP. B103 cells transfected with both wild-type (B103/APP) and mutant APP construct (B103/APPΔNL) secreted comparable amounts of soluble forms of APP (sAPP). B103/APP cells produced sAPP and cleaved at amyloid β/A4 (Aβ) 16, the α-secretase site, and B103/APPΔNL cells produced sAPPβ cleaved at Aβ 1, the β-secretase site. B103/APPΔNL cells developed fewer neurites than B103/APP cells in a serum-free defined medium. Neurite numbers of parent B103 cells were increased by the 50% conditioned medium (CM) from B103/APP cells but reduced by the CM from B103/APPΔNL cells. Chemically synthesized Aβ at concentration levels higher than 1 nM reduced numbers of neurites from B103 or B103/APPΔNL cells. However, Aβ at 1–100 nM could not reduce the neurite number of B103/APP cells. The protective activity against Aβ's deleterious effect to reduce neurite numbers was attributed to sAPPα in the CM. Although sAPPα could block the effect of Aβ, sAPPβ could not do so under the identical condition, suggesting the importance of the C-terminal 15-amino acid sequence in sAPPα. Nevertheless, sAPPα's protective activity required the N-terminal sequence around RERMS, previously identified to be the active domain of sAPPβ. The overall effect of APP mutation which overproduced Aβ and sAPPβ and underproduced sAPPα was a marked decline in the neurotrophic effect of APP. We suggest that the disruption of balance between the detrimental effect of Aβ and the trophic effect of sAPP may be important in the pathogenesis of AD caused by this pathogenic APP mutation © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 469–480, 1997     

Marriage Timing over the Generations

Strong relationships have been hypothesized between the timing of marriage and the familial environment of the couple. Sociologists have identified various mechanisms via which the age at marriage in the parental generation might be related to the age at marriage of the children. In our paper we study this relationship for historical populations. We use a dataset consisting of several hundreds of thousands of marriages contracted in three of the 11 Dutch provinces between 1812 and 1922. We identified the generational links between the brides, grooms, their parents, and grandparents. We studied (a) whether there is a relationship between ages at marriage of (grandfathers) fathers and sons, and ages at marriage of (grandmothers) mothers and daughters and (b) whether this relationship might be explained by social class. We find evidence for a clear effect of the family on age at marriage and substantial intergenerational transmission. The impact that the family of origin has on age at entry into marriage can partly be attributed to social class. We also observed positive effects of grandparents’ age at marriage on their offspring’s age at marriage.

Parkin stabilizes PINK1 through direct interaction

Parkinson disease (PD) is the most common movement disorder and is characterized by dopaminergic dysfunction. The majority of PD cases are sporadic; however, the discovery of genes linked to rare familial forms of the disease has provided crucial insight into the molecular mechanisms of disease pathogenesis. Multiple genes mediating familial forms of Parkinson’s disease (PD) have been identified, such as parkin (PARK2) and phosphatase and tensin homologue deleted on chromosome ten (PTEN)-induced putative kinase 1: PINK1 (PARK6). Here, we showed that Parkin directly interacts with PINK1, but did not bind to pathogenic PINK1 mutants. Parkin, but not its pathogenic mutants, stabilizes PINK1 by interfering with its degradation via the ubiquitin-mediated proteasomal pathway. In addition, the interaction between Parkin and PINK1 resulted in reciprocal reduction of their solubility. Our results indicate that Parkin regulates PINK1 stabilization via direct interaction with PINK1, and operates through a common pathway with PINK1 in the pathogenesis of early-onset PD.     

Animal models of human amyloidoses: Are transgenic mice worth the time and trouble?

The amyloidoses are the prototype gain of toxic function protein misfolding diseases. As such, several naturally occurring animal models and their inducible variants provided some of the first insights into these disorders of protein aggregation. With greater analytic knowledge and the increasing flexibility of transgenic and gene knockout technology, new models have been generated allowing the interrogation of phenomena that have not been approachable in more reductionist systems, i.e. behavioral readouts in the neurodegenerative diseases, interactions among organ systems in the transthyretin amyloidoses and taking pre-clinical therapeutic trials beyond cell culture. The current review describes the features of both transgenic and non-transgenic models and discusses issues that appear to be unresolved even when viewed in their organismal context.     

家族性高胆固醇血症患者低密度脂蛋白受体基因复合杂合突变分析

目的:对1例临床确诊为纯合型家族性高胆固醇血症(FH)先证者及其核心家系成员进行基因检测分析,探讨患儿发病的分子病理基础.方法:收集先证者及父母血标本及临床资料,酚氯仿法提取基因组DNA,DNA直接测序方法检测低密度脂蛋白受体(LDL-R)基因18个外显子和启动子及载脂蛋白B(ApoB100)R3500Q位点,核苷酸序列分析结果与Gen Bank比对寻找突变.结果:(1)先证者三尖瓣轻度关闭不全,先证者父母双侧颈总动脉内-中膜增厚,先证者母亲左侧颈内动脉起始处后壁多发混合回声斑块(2)该家系排除ApoB100基因R3500Q突变;(3)先证者LDL-R基因第13外显子发生A606T和D601Y复合杂合突变,前者第1879位G→A碱基置换,导致丙氨酸改变为苏氨酸,后者为1864位G>T碱基置换,导致天冬氨酸改变为酪氨酸,其父为携带A606T突变的杂合子,其母为携带D601Y突变的杂合子.结论:先证者LDL-R基因存在A606T和D601Y复合杂合突变,它们分别来源于父系及母系遗传.     

Freshwater finfish biodiversity and conservation: an asian perspective

Aspects on biodiversity and conservation of the ichthyofauna in the Asian region, in comparison to that of Africa, Europe and North America have been relatively less documented. This paper attempts to evaluate the above aspects in the East, and South and Southeast Asia based on available information in the literature. The familial diversity in inland waters in Asia (121 families) is considerably higher than in African and Latin American. Also, the finfish faunal diversity of 21 major river basins in East, and South and Southeast Asian indicate that species diversity is not necessarily related to familial diversity. The fish fauna in the region considered presently is highly diverse with an estimated cumulative total of 7447 species. Amongst the freshwater fishes the dominant groups are cyprinids (Cyprinidae, about 1000 species), loaches (about 400 species) of the families Balitoridae and Cobitiidae, gobids (Gobiidae, 300 species), catfishes (Bagridae, about 100 species), and the Osphronemidae (85 species). In the region, 462 freshwater finfish species are reckoned to be threatened, accounting for 17.5% of the all finfish species in this status in the world. In the region there are 66 species that are critically endangered and/or endangered, of which 32 are cyprinids, 14 of which are endemic to Lake Lanao, Mindano Island, Philippines. The diversity of freshwater fish species in the region was significantly related to the land area of the different countries in the following manner: