Avoidance behavior in rats selectively bred for differential alcohol sensitivity

Most affected (MA) and least affected (LA) rats, bred for extremes in motor impairment following an alcohol challenge, differed in their performance on two active avoidance tasks. In two-way shuttle avoidance, the MA line performed significantly better than the LA group, both in terms of response latencies and percent avoidances. The inferior performance of the LA line persisted across the 15 days of testing, and appeared to reflect an difference in asymptotic performance levels. In one-way avoidance, the MA line showed significantly better acquisition than the LA group; however, this difference dissipated across the 3 days of training. When tested following alcohol administration in either the one-or two-way avoidance paradigm, the MA rats showed a greater performance deficit than LA animals. These data were interpreted as indicating the generality of alcoholrelated line differences to a situation motivated by aversive consequences. Moreover, the line difference in avoidance acquisition represents one of the few non-drug-related phenotypic differences that have been found in these lines. In previous generations, disparate base rates of wheel running have been reported, and the data presented here confirm and extend this finding.     

Factors involved in the differential response to ethanol,barbital and pentobarbital in rats selectively bred for ethanol sensitivity

Two lines of rats, least affected (LA) and most affected (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.     

Central nervous system hemangioblastomas, endolymphatic sac tumors, and von Hippel-Lindau disease

Von Hippel-Lindau disease (VHL) is a hereditary cancer syndrome caused by germline mutations of the VHL tumor suppressor gene. Major progress has been made in the last decade in both clinical and fundamental aspects of VHL. The VHL gene product, pVHL, has major and multiple functions: pVHL regulates not only first angiogenesis but also extracellular matrix formation and the cell cycle. A molecular diagnosis of VHL is now available, leading to a transformation in clinical management of patients and their families. Diagnosis of VHL has to be suspected in patients with a VHL-related tumor without familial history and especially in case of hemangioblastoma or endolymphatic sac tumors. Such patients should be systematically investigated for clinical and molecular evidence of VHL disease. Treatment of symptomatic hemangioblastomas remains mainly neurosurgical, often in emergency, but stereotactic radiosurgery is emerging as an alternative therapeutic procedure. In the future, antiangiogenic drugs could represent a potential medical treatment of CNS hemangioblastomas in view of their highly vascular structure. Lastly, visceral manifestations of VHL disease are also of critical importance and require early detection for effective treatment. Received: 22 January 2000 / Accepted: 21 February 2000     

亚甲基四氢叶酸还原酶基因多态性与甘肃汉族2型糖尿病肾病的关系

目的 研究亚甲基四氢叶酸还原酶(MTHFR)基因多态性与汉族2型糖尿病肾病的关系。方法 应用聚合酶链反应—限制性片段长度多态性的方法，检测甘肃汉族人2型糖尿病患者91例，其中单纯糖尿病组50例，糖尿病肾病组41例，正常对照组35例，比较各组间MTHFR等位基因和基因型频率。结果 纯合基因型TT和杂合基因型CT在糖尿病肾病组的频率为34．1％和51．2％，高于糖尿病组(16％和48％)和正常对照组(14.3％和25．7％)，糖尿病肾病组的等位基因T频率(59．8％)也高于糖尿病组(40％)和正常对照组(27．1％)，差异均有统计学意义，糖尿病组和正常对照组之间的分布无统计学差异。结论 MTHFR基因C677T变异与甘肃汉族2型糖尿病患者糖尿病肾病的发病有关，等位基因T可能是糖尿病肾病的易感基因。     

近交系小鼠H-2基因的PCR检测方法

目的建立快速、灵敏、简便的H-2基因检测方法。方法针对近交系小鼠的H-2D区和H-2K区序列,设计两对特异性引物,分别进行DNA扩增,扩增产物通过聚丙烯酰胺凝胶电泳,确定H-2基因型。结果通过PCR反应扩增小鼠H-2D区和H-2K区的基因产物,可以区分不同的近交系小鼠的H-2基因型,进而可以区分出不同品系的近交系小鼠。结论利用分子生物学方法进行近交系小鼠遗传学检测,弥补了过去各种方法的不足,并且PCR方法还具备快速、简便、成本低廉、便于普遍推广并易于和国际接轨等优点。所以通过PCR方法可以进行小鼠H-2基因型检测。     

干扰素γ基因内含子1+874位点多态性与乙型肝炎病毒感染关系的研究

目的 研究干扰素γ（IFN-γ）基因内含子1＋874位点多态性与乙型肝炎病毒（HBV）感染、转归的关系,探讨慢性HBV感染的遗传易感因素.方法 采用序列特异性引物-聚合酶链反应（PCR-SSP）技术检测231例慢性HBV携带患者、165例自限性HBV感染者和135名正常对照者IFN-γ基因内含子1＋874位点T/A单核苷酸多态性.结果 慢性HBV感染组IFN-γ基因＋874位点AA基因型频率（TT、TA、AA频率分别为9.1%、12.1%、78.8%）高于正常对照组（TT、TA、AA频率分别为12.6%、23.0%、64.4%）（x2=9.60,P=0.008）;而自限性HBV感染组（TT、TA、AA频率分别为13.9%、23.7%、62.4%）和对照组之间差异无显著性（x2=0.16,P=0.92）.结论 IFN-γ基因内含子1＋874位点多态性与慢性HBV感染有关,该位点多态性可能在决定个体HBV感染遗传易感性方面有一定意义.     

Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis

The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n=72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients and controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis. Received: 14 February 2000 / Received in revised form: 20 April 2000 / Accepted: 4 June 2000     

成骨不全家系一个新的Ⅰ型胶原α1链蛋白基因突变

目的 对Ⅰ型胶原α1链蛋白基因（COL1A1基因）进行测序研究，旨在寻找已知或未知的COL1A1基因突变位点，探讨我国成骨不全的发病机制。方法 研究一常染色体显性遗传成骨不全家系的临床特征，设计引物对家系中患者和正常人的COL1A1基因外显子进行扩增和测序分析，同时对群体中无血缘关系的50名健康对照者进行限制性内切酶分析。结果 发现家系中成骨不全患者COL1A1基因的第3470位点的碱基G→A的突变，导致G1157D，而在家系内非患者及正常对照者中均无发现。结论 COL1A1基因突变也是中国人群中成骨不全致病原因之一，现发现的突变属成骨不全一个新的致病基因突变。甘氨酸转变成天冬氨酸的这种突变对成骨不全表型具有重要的影响。