MJD1基因单个碱基多态性与CAG重复序列不稳定性的关系

马查多－约瑟夫病患者的ＭＪＤ１基因存在ＣＡＧ三核苷酸不稳定扩展突变，为探讨这种不稳定扩展突变的分子机制。方法对５８名正常人和２０名ＭＪＤ患者的ＭＪＤ１基因内ＣＡＧ／ＣＡＡ、ＣＧＧ／ＧＧＧ两个位点的多态性进行检测。结果正常染色体中，具有ＣＧＧ等位基因的ＣＡＧ重复数目（２７．３２±０．６１，ｎ＝２８）较具有ＧＧＧ等位基因的ＣＡＧ重复数目（１５．９０±０．６９，ｎ＝３０）明显大（Ｐ＜０．０１）。ＣＧＧ等位基因在患者中的分布频率（１００％）明显高于正常人（４８．３％）。结论ＭＪＤ１基因内单个碱基置换影响ＣＡＧ重复序列的稳定性。     

三核苷酸重复的检测在脊髓小脑型共济失调的应用研究

目的建立中国人遗传性脊髓小脑型共济失调（ＳＣＡ）患者的ＳＣＡ１、ＳＣＡ２、ＳＣＡ３／ＭＪＤ、ＳＣＡ６型的ＣＡＧ三核苷酸重复（ＣＡＧ）ｎ频率的检测方法并探讨其诊断意义。方法应用聚合酶链式反应（ＰＣＲ）和６％变性聚丙烯酰胺凝胶电泳技术,检测了３０例正常人和６例临床诊断为ＳＣＡ患者上述４型的（ＣＡＧ）ｎ重复数。结果３０例正常人（ＣＡＧ）ｎ的重复数目分别为ＳＣＡ１６～４０次,ＳＣＡ２２２～２９次,ＳＣＡ３１３～３６次,ＳＣＡ６４～１６次。６例ＳＣＡ患者中２例有ＳＣＡ３异常,（ＣＡＧ）ｎ重复数分别为６７和７５,而ＳＣＡ１、ＳＣＡ２、ＳＣＡ６型（ＣＡＧ）ｎ重复数均在正常范围内。结论研究三核苷酸重复频率的检测为ＳＣＡ患者提供了准确可靠的诊断方法和标准。     

重症肌无力患者烟碱型乙酰胆碱受体抗体致鼠脑干？…

目的神经肌接头（ＮＭＪ）处乙酰胆碱（ＡＣｈ）传递障碍，是重症肌无力（ＭＧ）发病机制，然而，近年有研究表明部分ＭＧ患者有中枢神经系统（ＣＮＳ）受损的症状和神经电生理方面的异常表现，本研究为探讨其机制。方法 从烟碱型乙酰胆碱受体抗体（ｎＡＣｈＲ－ａｂ）阳性的全身型ＭＧ患者血清中提取ＩｇＧ将其注入ＳＤ大鼠脑室系统，观察其对脑干听觉诱发电位（ＢＡＥＰ）的影响。结果 ｎＡＣｈＲ－ａｂ使脑干听觉传导功能异常，     

遗传性脊髓小脑型共济失调患者SCA1基因突变检测分析

检测中国人遗传性脊髓小脑型共济失调（ＳＣＡ）患者的ＳＣＡ１基因突变［（ＣＡＧ）ｎ］。方法应用聚合酶链（ＰＣＲ）技术，检测了２７个ＳＣＡ家系中４４例ＳＣＡ患者的ＳＣＡ１（ＣＡＧ）ｎ。结果首次发现１个家系２例患者及１位“正常者”均有１个ＳＣＡ１异常等位基因扩增片段。患者Ⅲ５与其１位兄弟（“正常者”）的异常等位基因扩增片段，长度为２７２ｂｐ，三核苷酸ＣＡＧ重复数为５３次，患者Ⅲ２的异常等位基因扩增片段，长度为２９９ｂｐ，ＣＡＧ重复数为６２次，均超出正常范围。另２６个家系４２例患者的等位基因扩增片段长度范围在１６４～２１８ｂｐ之间，ＣＡＧ重复数在１７～３５次间，属于正常范围。结论来自１家系２例ＳＣＡ患者的基因分型为ＳＣＡ１型，“正常者”可能是未到发病年龄的无症状ＳＣＡ１患者，余２６个家系４２例患者不是ＳＣＡ１型。     

重症肌无力中枢神经系统受损模型

目的近年研究结果表明，重症肌无力（ＭＧ）病变部位并不仅仅局限于神经肌接头（ＮＭＪ）处突触后膜烟碱型乙酰胆碱受体（ｎＡＣｈＲ），烟碱型乙酰胆碱受体抗体（ＡＣｈＲ－ａｂ）病理作用可能波及到中枢神经系统（ＣＮＳ）。因此，有必要建立模拟ＭＧ患者ＣＮＳ损害的动物模型，研究ＭＧ患者脑脊液中存在的ＡＣｈＲ－ａｂ引起ＣＮＳ损害的机制。方法从ＭＧ患者血中提取的ＡＣｈＲ－ａｂ经侧脑室穿刺注入到大鼠脑室系统，然后观察其症状和体征，以及用脑干听觉诱发电位仪（ＢＡＥＰ）检测鼠脑干听觉传导中枢功能。用免疫组化法（ＡＢＣ）研究ＡＣｈＲ－ａｂ与ＣＮＳ神经－ｎＡＣｈＲ之间免疫结合反应及其分布。结果大鼠除了出现脑干听觉传导中枢功能障碍外，还出现类似于ＭＧ动物模型表现的症状。免疫组化研究结果显示，神经－ｎＡＣｈＲ样阳性免疫反应广泛分布于ＣＮＳ许多部位。结论脑室内注入的ＡＣｈＲ－ａｂ与神经－ＡＣｈＲ结合引起ＣＮＳ功能障碍和出现ＭＧ动物模型样症状。我们首次建立的中枢受损的ＭＧ模型将有助于阐明ＡＣｈＲ－ａｂ引起中枢受损和ＣＮＳ下位运动神经元引起横纹肌收缩无力的机制。     

先天愚型红细胞膜酶活性的研究

测定３２例先天愚型（ＤＳ）红细胞膜（Ｎａ、Ｋ）－ＡＴＰ酶、（Ｃａ、Ｍｇ）－ＡＴＰ酶活性及７例ＤＳ患者三磷酸甘油醛脱氢酶（Ｇ３ＰＤ）活性，结果发现：ＤＳ红细胞膜（Ｎａ、Ｋ）－ＡＴＰ酶、（Ｃａ、Ｍｇ）－ＡＴＰ酶活性与正常对照组无显著性差异，Ｇ３ＰＤ活性明显高于对照组，差别具有显著性，提示先天愚型红细胞膜存在能量代谢的异常。     

亨廷顿氏病发病及基因诊断

亨廷顿氏病（Ｈｕｎｔｉｎｇｔｏｎｓ，ｄｉｓｅａｓｅ，ＨＤ）是神经系统一种严重的常染色体显性遗传病［１］。该病的遗传学基因是在ＩＴ１５基因的开放阅读框架的５’端有一个多态的（ＣＡＧ）ｎ三核苷酸重复序列异常扩增，在正常人群中其拷贝数为１１～３４，而ＨＤ...     

经DNA测序证实的脊髓小脑性共济失调SCA3基因突变研究

目的 研究Ｍａｃｈａｄｏ－Ｊｏｓｅｐｈ病（ＭＪＤ）的基因突变及临床特征。方法 应用ＰＣＲ方法结合测序技术,检测了临床诊断脊髓小脑性共济失调（ＳＣＡ）的１１个家系２７例病人,４例散发ＳＣＡ及３５名家系中“正常人”的基因突变,并利用ＡＢＩ３７３测序仪对１例ＭＪＤ与１例症状前ＭＪＤ两对等位基因片段分别进行ＤＮＡ测序。结果 检出９个家系为ＭＪＤ,其中２个ＭＪＤ家系检测到６例症状前ＭＪＤ。正常等位基因三核苷     

异常PrP沉积对人朊蛋白病的临床和病理影响

目的　探讨异常ＰｒＰ沉积形式与ＣｒｅｕｔｚｆｅｌｄｔＪａｋｏｂ 病（ＣＪＤ）、ＧｅｒｓｔｍａｎｎＳｔｒａｕｓｓｌｅｒ 综合征（ＧＳＳ）临床与病理关系。方法　经病理检查确诊的７ 例ＣＪＤ,１ 例ＧＳＳ脑切片进行朊蛋白ＰｒＰ免疫组化染色和实验动物传递。结果　（１） ７ 例ＣＪＤ均呈现突触型阳性,而ＧＳＳ则呈现斑块型阳性;（２） 突触型阳性者,病程短,平均１２ ．３ 个月,斑块型阳性者病程６０ 个月;（３） ７ 例突触型均有痴呆,６ 例有肌阵挛,小脑症状不明显,斑块型则与其相反;（４） 突触型中４ 例进行动物传递均获成功,斑块型则否;（５） 突触型ＰｒＰ沉积多位于大脑灰质,斑块型多在小脑分子层。结论　应用水解高压灭菌法,以ＰｒＰ抗血清为第一抗体的免疫组化方法,可以准确判定异常ＰｒＰ沉积的两种类型,二者神经症状、病程长短、脑电图改变以及动物传递结果等均不相同。     

糖皮质激素受体阻断对大鼠实验性自身免疫性重症肌无力的影响

研究重症肌无力（ＭＧ）患者外周血白细胞糖皮质激素受体（ＧＲ）减少，而血浆皮质醇则在正常范围，探讨其与ＭＧ发病的关系。方法ＳＤ大鼠３２只，随机分成４组。实验组先以ＧＲ的竞争性拮抗剂米非司酮（ＲＵ３８４８６，ＲＵ４８６）阻断其ＧＲ，再以从人肌肉中粗提的乙酰胆碱受体（ｎＡＣｈＲ）进行免疫；实验对照组单用ｎＡＣｈＲ，试剂对照组只用ＲＵ４８６，而正常对照组仅用福氏佐剂。以临床症状、血清抗ｎＡＣｈＲ抗体（ｎＡＣｈＲ－ａｂ），重复刺激坐骨神经递减幅度为观察指标。结果实验组的临床症状和ｎＡＣｈＲ－ａｂ滴度升高及肌电图递减幅度均较明显，经ｔ检验分析，均与实验对照组有显著性差异（Ｐ＜０．０５），而试剂对照组和正常对照组均无ＭＧ的表现。结论ＧＲ被阻断后，对大鼠的实验性自身免疫性ＭＧ（ＥＡＭＧ）发病有易化作用。     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

Abstract

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Presence and severity of anorexia and bulimia among male and female Omani and non-Omani adolescents

OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities providing a natural setting for studying the cross-cultural differences in the presence and severity of eating disorders as well as an opportunity for evaluating the performance of measurement instruments for these disorders. METHOD: Disordered eating screening instruments (the Eating Attitude Test and the Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of males and 10.6% females) showed a propensity for anorexic-like behavior. On the Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani teenagers, 18.4% showed a tendency toward bulimia, with females showing a slightly greater tendency than males. In contrast, barely 2% of Omani adults showed either a presence of or a severity of disorderly behavior with food. CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups and Omani adults. This finding is discussed in the light of emerging evidence from many parts of the world suggesting that cultural transition, compounded by demographic constraints, plays a significant role in abnormal eating attitudes.     

Relationship Between Sluggish Cognitive Tempo and Age and IQ in Preschool and School-Age Children and Adolescents with Autism and with ADHD

Journal of Autism and Developmental Disorders - Relationships between sluggish cognitive tempo (SCT) and age and IQ were investigated in children with autism and/or ADHD covering broader age and IQ...     

Synaptic plasticity and learning and memory: LTP and beyond.

Long-term potentiation (LTP) of synaptic activity is by far the most popular and widely researched model of synaptic plastic changes that might occur during learning. Numerous recent reports, however, have not found a correlation between the inducibility of LTP in the hippocampus and the ability of animals to learn hippocampus-dependent tasks. For example, some experiments with gene deletion (knockout) mice strains have shown that in some strains LTP is not inducible in the dentate gyrus, in area CA3, or CA1, but the animals are still able to learn spatial tasks. This apparent mismatch has rejuvenated the discussion concerning whether LTP is a good model for mechanisms that underlie memory formation in the nervous system. This review analyzes the conditions under which LTP is induced or learning takes place and suggests reasons for the mismatches that can occur and what we can learn from them. High-frequency stimulation protocols and in vitro assays cannot be seen to resemble natural firing patterns or conditions found in the brain. More physiological experimental conditions, especially in vivo recording in awake animals, could lead the way to the development of improved models of learning mechanisms that better correlate with learning abilities of animals.