背景：青少年肥胖正在成为一个全国性的公共健康问题。包括西布曲明(sibutramine)在内的减肥药物不但有利于成人的体重控制而且可将其与行为治疗(behavior therapy，BT)结合用于青少年肥胖。目的：在一项以家庭为基础的行为体重控制计...背景：青少年肥胖正在成为一个全国性的公共健康问题。包括西布曲明(sibutramine)在内的减肥药物不但有利于成人的体重控制而且可将其与行为治疗(behavior therapy，BT)结合用于青少年肥胖。目的：在一项以家庭为基础的行为体重控制计划中，检验加用西布曲明是否可以提高青少年肥胖的减肥效果。设计、地点和参加者：于1999年3月至2002年8月在一大学诊所进行的随机双盲、安慰剂对照试验。82例参试青少年的年龄13—17岁，体重指数(body mass index，BMI)32—44。先治疗6个月，然后开放标记(简称：开标，open—label)继续治疗7—12个月。干预：头6个月，参试者或者接受BT加西布曲明或者接受BT加安慰剂。从第7-第12个月，所有参试者均接受开标西布曲明治疗。主要观察指标：BMI变化百分率；收缩压、舒张压、脉搏以及饥饿(感)。结果：在6个月的意向-治疗分析中，BT加西布曲明组平均(SD)体重减轻7．8kg(6．3kg)，BMI下降8．5％(6．8％)，显著大于BT加安慰剂组的3．2kg(6．1kg)和4．0％(5．4％)。接受西布曲明的参试者报告饥饿感亦显著减轻(P=0．002)。第7～12个月，最初用西布曲明治疗的青少年，继续使用该药，体重上升0．8kg(10．5kg)；停用安慰剂改服西布曲明的青少年体重进一步减轻1．3kg(5．4kg)。减少药物剂量(n=23)或者停用(n=10)以控制血压、心率或其他症状的加重。结论：在综合行为治疗计划中，加上西布曲明可导致较行为治疗加安慰剂更为显著的体重减轻。在获得更广泛的安全性和有效性数据前，减肥药只宜在试验的基础上用于儿童和青少年。展开更多
Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been pr...Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.展开更多
Huntington＇s disease （HD） is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of ...Huntington＇s disease （HD） is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of subpopulations of neurons in the brain, however the precise underlying mechanisms how a ubiquitously expressed disease protein could target specific types of neurons for degeneration remains a critical, yet unanswered question for HD and other major neurodegenerative disorders. In this review, we describe the expanding view of selective neuronal vulnerability in HD, based on recent neuropathological and neuroimaging studies. We will also summarize the systematic effort to define the cell types in which mutant Huntingtin expression is critical for pathogenesis of vulnerable neurons in the striatum and cortex. Finally, we will describe selected, emerging molecular mechanisms that are implicated in selective disease processes in HD. Together, the field has begun to appreciate the distinct molecular pathogenic roles of mutant huntingtin in different cell types that may contribute to the selective neuronal vulnerability, with dissection of such mechanisms likely to yield novel molecular targets for HD therapy.展开更多
文摘背景：青少年肥胖正在成为一个全国性的公共健康问题。包括西布曲明(sibutramine)在内的减肥药物不但有利于成人的体重控制而且可将其与行为治疗(behavior therapy，BT)结合用于青少年肥胖。目的：在一项以家庭为基础的行为体重控制计划中，检验加用西布曲明是否可以提高青少年肥胖的减肥效果。设计、地点和参加者：于1999年3月至2002年8月在一大学诊所进行的随机双盲、安慰剂对照试验。82例参试青少年的年龄13—17岁，体重指数(body mass index，BMI)32—44。先治疗6个月，然后开放标记(简称：开标，open—label)继续治疗7—12个月。干预：头6个月，参试者或者接受BT加西布曲明或者接受BT加安慰剂。从第7-第12个月，所有参试者均接受开标西布曲明治疗。主要观察指标：BMI变化百分率；收缩压、舒张压、脉搏以及饥饿(感)。结果：在6个月的意向-治疗分析中，BT加西布曲明组平均(SD)体重减轻7．8kg(6．3kg)，BMI下降8．5％(6．8％)，显著大于BT加安慰剂组的3．2kg(6．1kg)和4．0％(5．4％)。接受西布曲明的参试者报告饥饿感亦显著减轻(P=0．002)。第7～12个月，最初用西布曲明治疗的青少年，继续使用该药，体重上升0．8kg(10．5kg)；停用安慰剂改服西布曲明的青少年体重进一步减轻1．3kg(5．4kg)。减少药物剂量(n=23)或者停用(n=10)以控制血压、心率或其他症状的加重。结论：在综合行为治疗计划中，加上西布曲明可导致较行为治疗加安慰剂更为显著的体重减轻。在获得更广泛的安全性和有效性数据前，减肥药只宜在试验的基础上用于儿童和青少年。
文摘Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.
基金Oakley Mental Health Foundation and Charitable Trust of the Auckland Faculty of the Royal New Zealand College of General Practitioners. The guarantor accepts full responsibility for the conduct of the study had access to the data and controlled the dec
文摘Huntington＇s disease （HD） is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of subpopulations of neurons in the brain, however the precise underlying mechanisms how a ubiquitously expressed disease protein could target specific types of neurons for degeneration remains a critical, yet unanswered question for HD and other major neurodegenerative disorders. In this review, we describe the expanding view of selective neuronal vulnerability in HD, based on recent neuropathological and neuroimaging studies. We will also summarize the systematic effort to define the cell types in which mutant Huntingtin expression is critical for pathogenesis of vulnerable neurons in the striatum and cortex. Finally, we will describe selected, emerging molecular mechanisms that are implicated in selective disease processes in HD. Together, the field has begun to appreciate the distinct molecular pathogenic roles of mutant huntingtin in different cell types that may contribute to the selective neuronal vulnerability, with dissection of such mechanisms likely to yield novel molecular targets for HD therapy.
