阿霉素肾病大鼠中肾小球nephrin表达与氧化应激反应的关系

目的：氧化和抗氧化失衡可能是肾病综合征产生大量蛋白尿的原因之一,而肾小球裂隙膜分子nephrin在维持肾小球滤过屏障功能中起着重要作用。因此该实验初步探讨阿霉素肾病大鼠肾小球裂隙膜分子nephrin表达与氧化应激反应的关系,以及泼尼松和维生素E对阿霉素大鼠肾损伤保护作用的机制。方法：尾静脉单次注射阿霉素5 mg/kg建立肾病发病过程中的氧化应激模型,并增加泼尼松和维生素E干预。应用化学比色法检测肾皮质氧化应激指标变化,应用免疫组织化学技术观察肾小球裂隙膜分子nephrin表达变化,并对两者进行相关性分析。结果：①肾病组大鼠肾皮质丙二醛（MDA）含量及24 h尿蛋白排泄量高于正常对照组,超氧化物歧化酶（SOD）和总抗氧化能力（T-AOC）活性低于正常对照组。与肾病组相比,泼尼松和维生素E干预组从14 d开始尿蛋白排泄量明显减少,直到28 d（P<0.05）。维生素E干预组肾皮质MDA含量较肾病28 d组下降,SOD、T-AOC活性较肾病28 d组升高。②正常对照组大鼠nephrin沿肾小球基底膜呈深褐色连续线性分布;肾病组随时间的延长深褐色连续线性分布向浅褐色短线条状或点状分布转化;泼尼松和维生素E干预组减轻了nephrin分子的异常改变;量化分析显示,肾病组肾小球nephrin阳性表达含量明显低于正常对照组,泼尼松及维生素E干预组肾小球nephrin阳性表达含量较肾病组增加。③肾小球nephrin蛋白阳性表达含量与肾皮质MDA含量呈负相关,与肾皮质SOD和T-AOC活性呈正相关。结论：肾小球裂隙膜分子nephrin表达减少与氧化应激反应密切相关;泼尼松和维生素E对阿霉素肾病大鼠肾损伤有保护作用。［中国当代儿科杂志,2009,11（1）：56-60］     

黄芪对IgA肾病大鼠蛋白尿及肾组织表达nephrin、podocin的影响

目的 观察黄芪对IgA肾病(IgAN)大鼠蛋白尿及肾组织nephrin、podocin的影响,探讨黄芪对IgAN蛋白尿的治疗作用及其机制.方法 24只6周龄SD大鼠分为对照组、模型组及黄芪组.模型组和黄芪组采用牛血清清蛋白+脂多糖+四氯化碳的方法进行IgAN造模,黄芪组予黄芪颗粒治疗,对照组予等量蒸馏水灌胃,9 g·L<'-1>盐水皮下注射及尾静脉注射.考马斯亮蓝法检测其24 h尿蛋白定量,全自动生化分析仪检测其血生化指标.应用直接免疫荧光法检测其肾小球IgA沉积强度,应用间接免疫荧光法检测肾小球nephrin、podocin蛋白的表达及分布,采用实时荧光定量PCR技术检测肾皮质nephrin mRNA和podocin mRNA的表达.结果 1.黄芪组大鼠尿蛋白较模型组显著减少,差异有统计学意义(P<0.01).2.黄芪组大鼠肾组织病变较模型组减轻.3.黄芪组大鼠肾小球nephrin表达量与模型组比较差异无统计学意义(P>0.05),但仍显著高于对照组(P<0.01);而podocin表达量较模型组显著降低(P<0.05);黄芪组大鼠肾皮质nephrin mRNA及podocin mRNA的表达均较模璎组及对照组显著升高(P<,a><0.01).4.黄芪组大鼠肾小球nephrin、podocin的不连续斑片状、团块状异常分布较模型组改善.结论 IgAN大鼠肾组织nephrin、podocin出现表达变化及分布异常,黄芪能减少IgAN大鼠尿蛋白,其作用可能与调节nephrin、podocin的表达及分布有关.     

αD_3对阿霉素肾病大鼠肾组织WT_1表达的影响

目的　该研究通过阿霉素肾病大鼠模型 ,动态观察α骨化醇 (αD3)对肾组织肾母细胞瘤抑制基因(WT1 )表达及其对肾病大鼠蛋白尿的影响。方法　 12 0只SD雄性大鼠随机分为对照组、肾病组、激素组、αD3组和联合组 (激素 +αD3) ,每组 2 4只。一次性尾静脉注射阿霉素制备阿霉素肾病模型 ,对照组一次性尾静脉注射同体积生理盐水。模型制备 2周后 ,激素组、αD3组和联合组分别每天灌服泼尼松、αD3及泼尼松与αD3,共 4周。对照组和肾病组分别灌服等量蒸馏水。于实验第 2 ,4 ,6周末各组随机抽取 8只大鼠 ,收集 2 4h尿标本后处死大鼠 ,分离肾组织 ,观察肾组织病变。用考马斯亮蓝法检测 2 4h尿蛋白含量 ,用间接免疫荧光法检测肾组织WT1 的表达。结果　第 2周末 ,肾病组、激素组、αD3组及联合组大鼠 2 4h尿蛋白含量高于对照组 ,差异有显著性意义 (P <0 .0 1) ,第 4周及第 6周末 ,肾病组大鼠尿蛋白逐渐上升 ,激素组、αD3组及联合组尿蛋白降低 ,均低于同时间点肾病组 ,差异有显著性意义 (P <0 .0 1) ;WT1 表达仅见于肾小球 ,肾小管几乎无表达。第 2周末 ,肾病组、激素组、αD3组及联合组大鼠WT1 表达明显低于对照组 (P <0 .0 1) ;第 4及第 6周末 ,肾病组WT1 表达进一步减弱 ,激素组、αD3组及联合组WT1 的表达增加     

生长因子β1对儿童哮喘的作用及孟鲁司特钠对其影响

目的 探讨生长因子β1在儿童哮喘中的作用及观察孟鲁司特钠对其的影响。方法 筛选2009年9月-2010年9月我院哮喘专病门诊轻度持续哮喘患儿60例及来院健康体检儿童30例,将哮喘患儿随机分成孟鲁司特钠组和安慰剂对照组;采用双抗夹心酶联免疫吸附试验( ELISA)、RT-PCR技术分别检测治疗前后患儿血浆中TGF-β1水平和外周血单个核细胞(PBMC)中TGF-β1mRNA表达;采用流式细胞技术,检测表达叉状头/翅膀状螺旋转录因子3的CD4T调节细胞(Foxp3+ CD4+ Treg)及各亚型的比例。结果 (1)血浆中TGF-β1水平：治疗前哮喘组[(11.51±1.12) ng/L]明显低于健康对照组[(47.92±1.52) ng/L](q=20.01,P＜0.01);治疗后,孟鲁司特钠组[ (20.03±1.14)ng/L]高于安慰剂组[(12.10±3.91) ng/L]（q=14.62,P＜0.05）,但均值仍低于健康对照组;(2)外周血单个核细胞中TGF-β1 mRNA表达：治疗前哮喘组(0.31 +0.07)明显低于健康对照组(0.61±0.2) (q =8.97,P＜0.05);治疗后,孟鲁司特钠组(0.46±0.13)表达高于安慰剂组(0.32±0.04)（q=8.25,P＜0.05）,但仍低于健康对照组;(3)流式细胞检测结果各组间比较差异有统计学意义(P＜0.05)：哮喘患儿与健康对照组相比,Foxp3+ CD4+ Treg细胞比例增加[(8.30±1.30)％,(6.05±1.80)％];其中CD45 RA+ Foxp3lo比例增高[(4.60±1.04)％,(3.27±1.03)％];CD45 RA - Foxp3h1比例降低[(0.75±0.13)％,(0.93±0.26)％];CD45 RA-Foxp3lo比例两组差异无统计学意义。治疗后,孟鲁司特钠组较安慰剂组,aTreg细胞占Foxp3+ CD4+ Treg比例增加[(1.16±0.24)％,(0.89±0.22)％],差异有统计学意义。结论哮喘儿童体内存在血浆及外周血单个核细胞中TGF-β1表达的降低,可能是导致哮喘发病的重要原因;孟鲁司特钠能有效改善TGF-β1的表达并通过调节Foxp3的表达来发挥治疗作用。     

获得性肾小球疾病肾组织中nephrin的表达

目的探讨nephrin在蛋白尿发生中的可能作用.方法用免疫组化及图象分析的方法,分别对临床表现为大量蛋白尿,单纯性血尿患儿及对照组肾组织切片上nephrin的表达进行检测.结果 (1) 大量蛋白尿组的nephrin表达量为0.62±0.24,与单纯性血尿组(0.67±0.23)及对照组(0.82±0.17)比较三者之间差异无显著意义(P＞0.05).(2)大量蛋白尿伴弥漫性足突融合组nephrin表达量为0.61±0.25,与大量蛋白尿不伴弥漫足突融合组(0.62±0.25)及对照组比较三者间差异无显著意义(P＞0.05).(3)弥漫足突融合微小病变组nephrin表达量为0.50±0.15,与非微小病变(0.65±0.27)及对照组比较差异无显著意义(P＞0.05).结论在获得性肾小球疾病中,用免疫组化的方法未能检测到肾小球nephrin的表达变化.     

双环醇对单侧输尿管梗阻大鼠肾间质纤维化的影响及其机制

目的 通过双环醇干预单侧输尿管梗阻(UUO)模型大鼠,动态观察核转录因子-κB(NF-κB)、细胞间黏附因子-1(ICAM-1)在梗阻侧肾间质中的表达,探讨双环醇延缓肾间质纤维化(RIF)的机制.方法 建立 UUO致肾间质纤维化大鼠模型,将81只大鼠随机分为假手术组、模型组、治疗组.治疗组于术后第1天开始给予双环醇200 mg/kg灌胃;假手术组和模型组给予等量生理盐水灌胃.在术后第7、14、21天每组各取9只处死,取动脉血分离血清测血肌酐和血尿素氮,观察大鼠肾功能变化.取梗阻侧肾组织行苏木精-伊红及Masson染色,观察肾脏病理学变化.用免疫组化方法检测肾组织NF-κB 、ICAM-1表达.结果 治疗组血清肌酐和尿素氮较模型组显著下降,差异有统计学意义(P ＜ 0.01).治疗组肾小管间质损伤评分和RIF相对面积均低于模型组(P均＜ 0.05).治疗组肾组织的NF-κB、ICAM-1蛋白表达显著低于模型组(P均＜ 0.05).结论 双环醇能够减轻UUO所致的肾间质损伤及RIF程度,其作用机制可能177(11):7485-7496.     

FTY720对肾大部切除大鼠肾小球硬化及细胞周期调节蛋白表达的影响

目的 观察FTY720对肾大部切除大鼠肾小球硬化的作用,探讨其作用机制.方法 采用肾大部切除制作肾小球硬化模型,分模型组和FTY720治疗组,设假手术组为正常对照组,每组8只.检测各组术前及术后第2、4、8、12周大鼠24 h尿蛋白,术前及术后8周、12周检测血尿素氮和肌酐以及残肾组织病理改变,并应用免疫组化方法检测Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)的表达水平及细胞周期调控蛋白p21、p27、细胞周期素E(cyclinE,CE)的表达.结果 模型组术后2周24 h尿蛋白升高至(8.07±1.61)mg/d,以后逐渐增高,12周达(28.6±12.21)mg/d,治疗组24 h尿蛋白量在术后4周为(9.90±1.49)mg/d,12周时为(11.35±2.09)mg/d,较模型组减低(P＜0.01).与假手术组相比,模型组8周血肌酐升高达(61.08±4.28)μmol/L,12周时为(130.20±23.90)μmol/L,升高更明显(P＜0.05);治疗组血肌酐则未见明显升高,12周时为(80.19±7.11)μmol/L,较模型组显著减低(P＜0.05);各组血尿素氮与肌酐变化相似.肾脏病理和免疫组化染色显示,FTY720能明显减轻大鼠硬化程度,抑制肾小球内细胞外基质Col-Ⅳ、FN的表达.细胞周期调控蛋白研究结果表明FTY720能升高肾小球p27表达,降低p21及CE表达.治疗组p21和CE表达明显低于模型组,但仍稍高于假手术组,p27明显高于模型组,与正常组无明显区别.结论 FTY720能显著降低肾大部切除大鼠的24 h尿蛋白量,防止肾小球硬化,其作用与调控细胞周期调节蛋白的表达,减少Col-Ⅳ、FN聚积有关.     

黄芪对IgA肾病模型大鼠免疫紊乱调节作用的研究

目的 探讨黄芪对IgA肾病(IgAN)模型大鼠免疫紊乱的调节作用.方法 采用口服牛血清白蛋白(BSA)、皮下注射四氯化碳(CCl4)加用尾静脉注射脂多糖(LSP)复合方法,复制IgAN模型大鼠.实验分为3组:正常组、模型组和黄芪治疗组;黄芪治疗组给予黄芪颗粒剂灌胃,正常组及模型组分别灌注等量蒸馏水.检测各组大鼠血尿、蛋白尿及肾脏病理改变,采用免疫组织化学技术检测各组大鼠肾组织中Th2类细胞因子转化生长因子β1(TGF-β1)、白细胞介素5(IL-5)表达情况,ELISA法检测血清中Th1类细胞因子干扰素γ(IFN-γ)和Th2类细胞因子白细胞介素4(IL-4)的水平.结果 ①IgAN模型组大鼠尿红细胞计数高于正常组和黄芪治疗组(P＜0.01);而IgAN模型组大鼠24 h蛋白尿亦高于正常组(P＜0.05)和黄芪治疗组(P＜0.05).②IgAN模型组大鼠肾小球系膜区、肾小管、肾间质病理损害较正常对照组和黄芪治疗组明显加重;模型组大鼠肾小球系膜区IgA免疫荧光较正常组和黄芪治疗组明显增强.③免疫组化结果显示,正常组肾组织有少量TGF-β1和IL-5表达,而IgAN模型组大鼠肾组织中TGF-β1和IL-5表达明显增强,与正常对照组和黄芪治疗组TGF-β1(P＜0.05)和IL-5(P＜0.05)比较差别有统计学意义.④模型组大鼠血清IL-4含量[(33.74±7.52)pg/ml]显著升高,与正常对照组[(2.36±0.85)pg/ml]和黄芪治疗组[(3.24±1.13)pg/ml]比较差别有统计学意义(P＜0.05);而模型组大鼠IFN-γ水平[(18.79±3.80)pg/ml]显著下降,与正常组[(46.53 ±5.56)pg/ml]和黄芪治疗组[(41.28±2.95)pg/ml]比较差别有统计学意义(P＜0.05).结论 黄芪可降低IgAN模型大鼠血尿和24 b蛋白尿水平,减轻肾脏病理变化及IgA在肾小球系膜区的沉积.可能的机制是通过调节IgAN模型大鼠Th1、Th2平衡紊乱,从而改善血清中Th类细胞因子IL-4和IFN-γ的水平,并减少肾组织中Th2类细胞因子TGF-β1和IL-5的表达,来延缓IgAN的发生发展.     

nephrin分子在多柔比星肾小球硬化大鼠模型中的表达

目的建立多柔比星肾小球硬化大鼠模型,通过检测nephrin分子表达探讨nephrin分子在肾小球硬化中的作用。方法清洁级雄性SD大鼠48只。体质量（200±20）g。随机分为模型组30只和对照组18只。模型组鼠尾静脉注射多柔比星5mg/kg,7d后重复尾静脉注射多柔比星3mg/kg建立大鼠肾小球硬化大鼠模型;对照组在对应时间点注射9g/L盐水。分别留取6和8周模型及对照组各6只大鼠尿液、血液及肾脏标本,分别检测24h尿蛋白、血生化,并进行肾脏光镜、电镜检查,提取肾脏RNA进行荧光定量PCR检测nephrin表达量。结果第6和8周模型组大鼠尿蛋白明显较对照组增加,血清清蛋白明显减低,BUN、Cr及血清胆固醇明显增高。肾脏病理在第6周时出现局灶肾小球硬化,第8周时呈典型肾小球硬化。模型组大鼠nephrin表达在第6和8周时明显较对照组增高,分别为对照组的3.85和6.15倍。结论nephrin分子在肾小球硬化大鼠模型表达明显增加,提示nephrin分子与蛋白尿发生与发展密切相关,并有可能参与肾小球硬化进展。     

孟鲁司特钠对哮喘小鼠气道重塑及Th17/CD4~+CD25~+Treg表达的影响

目的探讨白三烯受体拮抗剂孟鲁司特钠干预哮喘小鼠后气道重塑及Th17细胞/CD4~+CD25~+调节性T细胞(CD4~+CD25~+Treg)表达的动态变化及其相关性。方法将Balb/c小鼠随机分成空白组、哮喘组、孟鲁司特钠组,每组经腹腔注射鸡卵清蛋白(OVA)和氢氧化铝混悬液致敏并雾化吸入2.5%OVA以制备哮喘气道重塑模型,空白组以生理盐水替代;孟鲁司特钠组雾化前给予孟鲁司特钠混悬液灌胃,空白组及哮喘组以生理盐水代替。3组分别在雾化2周、4周及8周后的24 h内随机处死8只小鼠。肺组织病理切片观察气道重塑程度;流式细胞技术检测脾组织中Th17、CD4~+CD25~+Treg细胞占CD4~+T细胞百分比。结果各时间点哮喘组和孟鲁司特钠组支气管总管壁厚度、平滑肌厚度均高于空白组(P0.05),干预8周时孟鲁司特钠组较哮喘组上述变化明显减轻(P0.05)。与空白组比较,各时间点哮喘组和孟鲁司特钠组均显示Th17细胞数增加,与气道重塑呈正相关(P0.05);而CD4~+CD25~+Treg细胞数逐渐降低,与气道重塑呈负相关(P0.05)。干预8周时孟鲁司特钠组与哮喘组比较,Th17细胞数显著下降(P0.05);而CD4~+CD25~+Treg细胞数明显增加(P0.05)。结论孟鲁司特钠干预哮喘小鼠后能减轻气道重塑的发生,且随着用药时间延长,改善越明显;机制可能是通过改善哮喘小鼠体内Th17/CD4~+CD25~+Treg的免疫紊乱,抑制气道炎症反应从而减轻或延缓气道重塑来起作用的。     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Psychopathologie du syndrome d’Asperger et « aspérigisation » de la société contemporaine

The author has attempted here to point out, just for a start, the characteristics of Asperger syndrome from the point of view of psychopathology through a rereading of Hans Asperger's original paper (1944). This thesis merits reevaluation, if for no other reason than to fill the gaps in operational diagnostics based on the DSM. It is found by rereading that Asperger's view of the principal disturbances of autistic psychopathy include a “disturbance of natural evidence” or a “crisis of common sense”. This question of natural evidence that he evokes with regard to autistic psychopathy corresponds to W. Blankenburg's natural evidence, which constitutes a key concept for comprehending schizophrenia in the form poor-symptom (“symptomarme Schizophrenie”) that he observes in the speech of his patient Anne Rau. One can deduce from this that in terms of fundamental disturbances, Asperger syndrome and this “symptom-poor” schizophrenia overlap at the level of loss of natural evidence. It is moreover possible to classify Asperger syndrome among the disturbances of spacing in the sense meant by the evolutionary psychiatry of A. Stevens and J. Price. The author then develops our comprehension of Asperger syndrome from the point of view of the perspective proposed by the notion of resilience in people with Asperger syndrome and of the possibility for them, through these mechanisms of adaptation, to find in the organization of the personality of the “as if” type a position of relative equilibrium. They concur or overlap in the creation of crutches, of borrowed personalities secondarily legitimated by the reaction of the socius. This will end up in the production of inventions and œuvres (works). Clearly, one rarely encounters several cases that one could consider pertinently to be “successful” Asperger syndrome. Finally, the author notes that one can find a sort of isomorphism between Asperger syndrome and contemporary society when he proposes the term “asperigisation” to characterize our society, given that the equilibrium between emotion and logic is strongly disturbed in these patients, in whom logic undergoes hypertrophy while emotion is impoverished. From this perspective, the author hopes to suggest reasons for the increase in the number of cases of Asperger syndrome in the clinical setting and in society in general in our contemporary era.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.