神经连接蛋白-4基因3’UTR区多态性与孤独症患儿的关系

目的探讨神经连接蛋白-4(Neuroligin-4)基因多态性与中国汉族儿童孤独症的关系。方法选取Neuroligin-4基因上3’UTR区2个多态性位点rs3810687和rs3810688作为遗传标记,应用双脱氧链终止测序法对92个孤独症核心家系276名成员进行等位基因和基因型测定。对孤独症患儿及其父母分别进行Hardy-Weinberg平衡检验。在孤独症核心家系中应用单体型相对危险度分析(HRR)及传递不平衡检验(TDT)分析等位基因与孤独症的关系。结果 1.孤独症患儿及其父母观察值和预期值间差异均无统计学意义(Pa>0.05),研究对象均符合Hardy-Weinberg遗传平衡法则。2.在92个孤独症核心家系中,TDT检验显示rs3810687位点存在传递不平衡,C等位基因由杂合子父母传递给患病子代的频率高于A等位基因,差异有统计学意义(χ2=4.500,P=0.044);rs3810688位点2等位基因传递差异无统计学意义(χ2=0.362,P=0.630),由杂合子父母传递给患病子女的等位基因频率未偏离50%理论值。3.HRR分析结果与TDT检验结果一致:rs3810687位点存在传递不平衡,差异有统计学意义(χ2=12.556,P=0.000);rs3810688位点未见传递不平衡,差异无统计学意义(χ2=0.326,P=0.568)。结论 Neuroligin-4基因rs3810687位点与儿童孤独症相关,支持Neuroligin-4基因是孤独症的候选基因。     

Shank3基因单核苷酸多态性与中国汉族儿童孤独症的关联

目的 探讨Shank3基因单核苷酸多态性(SNPs)与中国汉族儿童孤独症之间的关系.方法 采用PCR与限制性片段长度多态性(PCR-RFLP)分析方法对82例孤独症儿童及80例健康儿童Shank3基因上的2个SNPs位点rs9616915和rs13057681的基因型和等位基因进行测定.采用病例-对照方法分析SNPs位点等位基因的分布,对孤独症组和健康对照组SNPs位点进行Hardy-Weinberg平衡检验.结果 1.健康对照组和孤独症组儿童观察值和预期值间差异均无统计学意义(Pa>0.05),即健康对照组和孤独症组均符合Hardy-Weinberg遗传平衡法则.2.二组儿童rs9616915和rs13057681位点等位基因频率和基因型分布上差异无统计学意义(rs9616915:基因型χ2=0.452,P>0.05;等位基因χ2=0.217,P>0.05;rs13057681:基因型χ2=0.256,P>0.05;等位基因χ2=0.173,P>0.05).结论 Shank3基因rs9616915和rs13057681SNPs片段与中国汉族儿童孤独症的发病无关,孤独症的易感基因有待于进一步研究.     

胃泌素释放肽受体基因多态性与儿童孤独症的关联研究

目的 探讨胃泌素释放肽受体(GRPR)基因第二外显子1106 C/T和1316 C/T单核苷酸多态性(SNP)在西安市汉族儿童中的分布特征及与孤独症(CA)的关系.方法 采用聚合酶连反应(PCR)技术,对59例孤独症患儿、82名正常对照儿童的2个SNP位点的基因型进行检测,通过测序进行验汪.用病例-对照和传递不平衡检验(TDT)分析SNP位点等位基因的分布,并对2个SNP位点的连锁、单体型及与孤独症行为的表现进行分析.结果 ①CA组和正常对照组GRPR基因第二个外显子1106和1316位点均有多态性表现,以TT基因型为主,未发现其他多态性位点.其中正常对照组儿童TT、TC、CC三基因型频率分别为68.3%、17.1%和14.6%,CA组分别为67.8%、16.9%和15.3%,各自按Hardy-Weinberg平衡温和度检验,差异无统计学意义(χ2=3.81、4.52,P均>0.05).两组基因型频率和等位基因频率分布差异无统计学意义(χ2=0.01、0.24,P均>0.05).②CA组儿童性别间基因型分布和等位基因分布差异无统计学意义(χ2=4.96、2.37,P均>0.05);正常对照组男女间TT、CT基因型分布差异有统计学意义(χ2=6.64,P<0.05),两组等位基因分布差异无统计学意义(χ2=2.04,P>0.05).③经秩相关性分析各基因型与描述儿童孤独症行为的ABC量表的总分和各因子分无相关性(rs=0.010～0.145,P均>0.05).结论 西安市汉族儿童中GRPR基因第二个外显子1106和1316位点存在基因多态性,并以TT基因型为主.未发现孤独症患儿和正常儿童间GRPR基因第二个外显子1106和1316基因多态性存在差异.正常对照儿童性别间TT、TC两组等位基因间存在差异.ABC量表的总分和各因子分与该基因多态性无相关性.     

神经连接蛋白-4基因单核苷酸多态性与孤独症患儿的关系

目的探讨神经连接蛋白-4(NLGN4X)基因单核苷酸多态性(SNPs)与中国汉族儿童孤独症的关系。方法应用聚合酶链式反应与限制性片段长度多态性(PCR-RFLP)分析方法对40例中国汉族孤独症儿童(孤独症组)及40例健康对照儿童(健康对照组)进行2个SNPs位点rs7049300和rs1882260的等位基因和基因型测定。用病例-对照分析SNPs位点等位基因的分布,对孤独症组和健康对照组SNPs位点进行Hardy-Weinberg平衡检验,采用SPSS12.0软件进行统计学分析。结果NLGN4X基因SNPs片段rs7049300和rs1882260的基因型分布频率符合Hardy-Weinberg(χ2=0.008、0.144,Pa>0.05),孤独症组和健康对照组在上述各位点等位基因频率和基因型分布均无统计学差异[rs7049300:χ2(基因型)=1.382,χ2(等位基因)=0.928,Pa>0.05;rs1882260:χ2(基因型)=0.811,χ2(等位基因)=0.921,Pa>0.05]。结论NLGN4X基因上的2个SNPs片段rs7049300和rs1882260与儿童孤独症的发病无关,孤独症的...     

孤独症儿童脆性位点精神发育迟滞1基因检测

目的对孤独症儿童进行脆性位点精神发育迟滞1(FMR-1)基因检测,探讨儿童孤独症与FMR-1基因的关系。方法孤独症患儿75例。用一般情况调查表进行调查,以儿童孤独症评定量表、孤独症行为检查量表筛查可疑患儿,按照中国精神障碍分类与诊断标准第3版(CCMD-3)的儿童孤独症诊断标准进行诊断和FMR-1基因检测。结果孤独症患儿FMR-1基因异常率极低,仅1.3%。结论儿童孤独症遗传学发病机制可能与FMR-1基因无关。     

孤独症2～6岁患儿亲子依恋状况及影响因素

目的 了解2～6岁孤独症患儿的亲子依恋特征,从家庭特征、父母特征和情感氛围等方面探讨孤独症患儿亲子依恋关系的可能影响因素.方法 以2007年1-6月在中山大学第三附属医院儿童发育行为中心就诊的55例孤独症患儿(男49例,女6例)及其父亲或母亲为研究对象.使用中国版幼儿依恋行为分类卡片测试孤独症患儿的依恋类型.专业测试人员指导家长按照卡片内容与儿童实际行为的符合程度(最符合到最不符合)进行9级评分,将90张卡片分成9组,从最不符合到最符合,构成每组10张的分布.每个被试的儿童会得到一组90个原始分数,然后将原始分数与同期健康儿童依恋安全性指标进行相关分析,得出的相关系数即为该儿童的依恋安全性得分.相关系数高于同期健康儿童依恋相关系数的第33百分位数者为安全型依恋,反之为不安全型.采用自编的<幼儿家庭生活情况调查表>了解孤独症患儿的家庭特征、父母特征和情感氛围等因素,分析孤独症患儿安全型依恋的影响因素.结果 55例孤独症患儿中,安全型依恋者16例,占29.1%;不安全型依恋者39例,占70.9%.对孤独症患儿亲子依恋关系影响因素的研究发现,孤独症患儿入托月龄越早,产生安全型亲子依恋关系的可能性越大(OR=0.87,95%CI=0.76~0.99);家庭气氛越好,产生安全型亲子依恋关系的可能性越大(P=0.03).结论 孤独症患儿的亲子依恋类型以不安全型依恋为主,入托年龄和家庭气氛影响孤独症患儿安全型依恋的产生.     

儿童攻击行为与COMT Val158Met及5-HTTLPR基因多态性关联分析

目的：探讨儿茶酚胺氧位甲基转移酶(COMT) 第158位密码子从缬氨酸到蛋氨酸的错义突变(Val158Met)多态性及5-羟色胺转运体（5-HTT）基因启动子区缺失/插入多态性（5-HTTLPR）是否为家庭暴力环境下儿童攻击行为的易感因素。方法：以家庭暴力环境下68例儿童作为研究对象,依据Achenbach儿童行为量表（父母卷）评分,其中24例为攻击行为高分组,44例为低分组。采用聚合酶链式反应 限制性片段长度多态性（PCR-RFLP）技术,检测两组COMT Val158Met和5-HTTLPR多态性,对所得基因型和等位基因频率进行对照和关联分析。结果：攻击行为高分组与低分组COMT Val158Met多态性的各基因型差异(χ2＝1.612,P=0.447)和等位基因频率差异(χ2=1.648,P=0.119)均无统计学意义。两组5-HTTLPR多态性的各基因型差异(χ2=1.807,P=0.405)和等位基因频率差异(χ2=0.403,P=0.527)亦无统计学意义。结论：本研究结果不支持COMT Val158Met和5-HTTLPR基因多态性是儿童攻击行为产生的易感因素。提示儿童攻击行为可能是多因素共同作用的结果。     

脑源性神经营养因子与儿童哮喘严重程度的关系

目的探讨血清脑源性神经营养因子(BDNF)水平与哮喘患儿病情严重程度的关系。方法选取60例哮喘急性发作期儿童(轻度组18例、中度组25例、重度组17例)及60例健康体检儿童作为研究对象,采用酶联免疫吸附法(ELISA)检测血清BDNF,分析BDNF水平与哮喘严重程度的关系。结果哮喘急性发作组及症状缓解组的BDNF水平均高于对照组,以急性发作组最高(P0.05);治疗后处于缓解期时,BDNF水平较发作期明显降低(P0.05)。发作期哮喘患儿病情严重程度不同,其血清BDNF水平不同:轻度组最低、重度组最高,差异有统计学意义(P0.05)。结论 BDNF可能在儿童哮喘的发病机制中发挥一定的作用,并且与病情严重程度相关。     

RAD50基因多态性与儿童急性淋巴细胞白血病的相关性

目的　探讨RAD50基因的SNP位点(rs17166050)的多态性与我国中部地区儿童急性淋巴细胞白血病(ALL)的相关性。方法　177例来自湖北武汉或其周边地区的ALL患儿和232例健康儿童作为研究对象。177例患儿中, 标危66例, 中危69例, 高危42例。利用PCR-RFLP的方法检测RAD50基因SNP位点多态性, 研究该多态性与ALL易感性及临床危险度的相关性。结果　ALL组的RAD50基因SNP位点的基因型(AA、GA、GG)分布与对照组相比差异有统计学意义(P=0.038), 且G等位基因与ALL易感性显著相关(OR=1.459, 95%CI：1.034~2.057, P=0.031); 但在ALL组中, 该SNP位点的多态性与ALL的危险度不相关。结论 RAD50基因的SNP位点(rs 17166050)的多态性与儿童ALL的易感性相关, 但与其危险度分层不具有相关性。     

IL-4R基因E375A、C406R、Q576R多态性与哈尔滨地区儿童哮喘发生的相关性

目的探讨IL-4R基因E375A、C406R、Q576R位点多态性与哈尔滨地区儿童哮喘发生的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,检测91例哮喘患儿和42例正常儿童的IL-4R基因型。结果哮喘组与对照组IL-4R基因1124核苷酸位点A→C突变(肽链E375A氨基酸位点),1902核苷酸位点A→G突变(肽链Q576R氨基酸位点),2位点基因型和基因频率差异无统计学意义(P>0.05);1216核苷酸位点T→C突变(肽链C406R氨基酸位点),3种基因型(CC、CR、RR)差异有统计学意义(P<0.05);变异型R等位基因频率中,哮喘组为22.94%,对照组为6.58%,两者差异有统计学意义(P<0.05),但该位点不符合Hardy-Weinberg平衡。结论IL-4R基因E375A,Q576R位点多态性可能与哈尔滨地区儿童哮喘发生无直接相关性。C406R位点有必要作进一步研究。     

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.     

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   

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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     

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.     

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.     

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.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

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.