mTOR基因多态性与儿童急性白血病的相关性分析

目的 探讨mTOR基因SNP位点(rs2295080)的多态性与中国中部地区儿童白血病以及白血病危险度的相关性.方法 采取病例对照研究方法,分别选取180例白血病患儿,其中急性淋巴细胞白血病(ALL)133例、急性粒细胞白血病(AML)47例,296例健康儿童(对照组)作为研究对象.利用PCR-RFLP方法测定SNP位点多态性分布,并进行统计分析.结果 ALL组、AML组以及对照组之间三种基因型分布差异有统计学意义(χ2=11.04,P=0.026);但三组之间等位基因G的频率分布差异无统计学意义(χ2=5.44,P=0.066).ALL组中GG基因型患病风险是对照组的3.180倍(OR=3.180, 95%CI:1.416~7.143,P=0.004);G等位基因是患ALL的危险因素(OR=1.456,95%CI:1.052~2.015).AML组中GG基因型患病风险是对照组的3.204倍(OR=3.204,95%CI:1.109~9.253);但G等位基因频率在AML组与对照相之间差异无统计学意义(OR=1.294,95%CI:0.792~2.115).ALL患儿标危、中危和高危三组之间基因型分布差异无统计学意义(χ2=2.16,P=0.340).结论 mTOR基因SNP位点(rs2295080)的多态性可能与ALL的易感性相关,G等位基因为风险因子.     

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。     

儿童特发性缺血性中风的临床和免疫遗传特征

目的探讨儿童特发性缺血性中风的临床和免疫遗传特征.方法对来自我国北方地区,临床表现和影像学检查均符合缺血性中风诊断标准的43例患儿(其中男27例,女16例;年龄1～11岁);采用微量淋巴细胞毒试验测定组织相容性复合体-Ⅰ(HLA-Ⅰ)中的A、B抗原;用PCR/SSO方法测定HLA-Ⅱ中的DRB1、DQA1和DQB1抗原.结果在HLA-A位点的抗原频率中,HLA-A空白位点频率与对照组相比显著增加[相对风险(RR)=8.126,χ     

肿瘤坏死因子-α基因启动子-238、-308位点G/A单核苷酸多态性与幼年特发性关节炎的相关性

目的 研究TNF-α基因启动子-238、-308位点G/A单核苷酸多态性与幼年特发性关节炎(JIA)及其各亚型间的相关性.方法 评估127例JIA患儿及106例健康儿童的临床资料.JIA的诊断和分型参照2001年国际风湿病学联盟标准.所有标本提取DNA后采用聚合酶链反应-限制性片段长度多态性方法进行TNF-α基因多态性分析.结果 1.JIA患儿和健康对照组TNF-α-238G和A等位基因表达频率分布:JIA患几分别为92.9%和7.1%,健康对照组为95.3%和4.7%,二组比较无统计学差异(X2=1.149P=0.284);而多关节型[类风湿因子(RF)阴性]与健康对照组比较有统计学差异(X2=7.621 P=0.006),其与A等位基因的表达有相关性(r=0.174 P<0.05).2.JIA患儿和健康对照组TNF-α-308 G和A等位基因表达频率分布:JIA患儿分别为94.1%和5.9%;健康对照组为95.3%和4.7%.二者比较无统计学差异(X2=0.322 P=0.571);而多关节型(RF阴性)与健康对照组比较亦有统计学差异(X2=7.621 P=0.006),其与A等位基因的表达有相关性(r=0.174 P<0.05).结论 TNF-α基因-238、-308位点A型基因在JIA关节损害中具有一定作用,为TNF-α在JIA治疗中提供间接依据.     

哮喘易感基因多态性与哮喘预测指数阳性婴幼儿喘息的相关性

目的探讨3个哮喘易感基因单核苷酸多态性(SNPs)位点与哮喘预测指数(API)阳性婴幼儿喘息的相关性。方法将201例喘息婴幼儿分为API阳性组(68例)和API阴性组(133例)。选取儿童哮喘易感基因SNPs位点ADRβ2R16G、FcεR1 E237G和IL13 A2044G,采用TaqMan探针法对两组患儿进行基因分型,分别比较上述基因多态性位点在阳性组和阴性组间的分布差异。结果多态性位点FcεR1 E237G AG杂合子在API阳性组的频率明显高于阴性组(分别为41.2%和24.1%),差异有统计学意义(χ2=6.30,P=0.012,OR=2.21,95%CI=1.18～4.13),而ADRβ2 R16G和IL13 A2044G位点在两组间的分布差异无统计学意义(χ2=1.72、1.85,P均>0.3)。结论儿童哮喘易感基因单核苷酸多态性FcεR1 E237G AG杂合子与API阳性患儿喘息相关,未发现ADRβ2 R16G和IL13 A2044G多态性与API阳性患儿喘息相关。     

干扰素γ和肿瘤坏死因子α基因单核苷酸多态性与宫内乙肝病毒感染易感性研究

目的探讨IFN_γ基因和TNF_α基因单核苷酸多态性(SNP)与HBV宫内感染的遗传易感因素。方法选择在确定时期内乙肝疫苗随访门诊定期随访儿童中凡属宫内HBV感染免疫失败者为Ⅰ组、未感染且免疫有效者为Ⅱ组,另选非HBV高危的健康儿童作对照组Ⅲ组,应用实时荧光定量PCR技术检测IFN_γ基因 874A/TSNP及CA重复序列,TNF_α基因-238G/A、-308G/ASNP。结果IFN_γ 874A等位基因频率Ⅰ组显著高于Ⅱ组和Ⅲ组(χ2=7.238、5.199,P均<0.05);CA重复序列12次频率(CA12) 明显低于Ⅱ组(χ2=7.548,P<0.01);TNF_α-238A等位基因频率Ⅰ组显著高于Ⅱ组和Ⅲ组(χ2=6.797、9.513,P均<0.01),-308位点等位基因频率Ⅰ组与Ⅱ组和Ⅰ组与Ⅲ组间差异无显著性(χ2=1.361、0.051,P均>0.05)。结论干扰素γ 874位点A等位基因占优势、IFN_γCA重复序列基因多态性和肿瘤坏死因子α-238A等位基因占优势对决定个体宫内HBV感染遗传易感性有一定意义,而TNF_α-308位点G/A等位基因单核苷酸多态性对个体乙肝病毒宫内感染易感性并无作用。     

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。     

IL-1β-511T基因rs16944多态性与热性惊厥的关联研究

目的 致热因子白细胞介素1（IL-1β）基因多态性是否参与热性惊厥（FS）的发病目前仍存在争议,该研究将探讨中国北方汉族儿童热点基因IL-1β-511T 的单核苷酸（SNP）rs16944 多态性与 FS 发病的关联性。方法 用 SNaPshot SNP 分型技术对 141 例单纯型 FS 患儿和 130 例健康对照进行 IL-1β-511T 基因rs16944 位点分型,比较该 SNP 基因型和等位基因频率的差异。结果 与对照组相比,病例组rs16944 多态性的基因型和等位基因频率差异均无统计学意义（P>0.05）;rs16944 多态性3 种基因型 A/A、A/G、G/G 的FS 患儿的临床特征比较,显示首次惊厥的年龄（χ2=19.491,Pχ2=9.317,Pχ2=26.798,P结论 IL-1β-511T 基因 rs16944 多态性与北方汉族儿童单纯FS 的发病无关联,但其基因型不同可能与患儿FS 的发生及预后有关。     

注意缺陷多动障碍与多巴胺-β-羟化酶基因的关联

目的 探讨注意缺陷多动障碍与多巴胺-β-羟化酶(DBH)基因内含子5 Taq Ⅰ酶切位点多态性是否关联.方法 采用聚合酶链反应限制性片段长度多态性(PCR-RFLP)分析技术,检测117例汉族注意缺陷多动障碍患儿及186名正常人群的DBH基因Taq Ⅰ位点的基因型及等位基因.结果 注意缺陷多动障碍患儿与正常对照组Taq Ⅰ位点的3种基因型比较,差异有高度统计学意义(χ2=10.35,P=0.006),等位基因之间比较,差异也有高度统计学意义(χ2=10.60,P=0.001).A1的OR95%CI为0.24～0.70,A2的OR95%CI为1.43～4.17.注意缺陷为主型Taq Ⅰ位点的3种基因型比较(χ2=7.58,P=0.023),等位基因比较(χ2=7.30,P=0.007),差异均有统计学意义.结论 DBH内含子5 Taq Ⅰ A2/A2基因型和A2等位基因,可能有增加注意缺陷多动障碍的患病趋势,是危险因子;A1可能有减少注意缺陷多动障碍的患病趋势,是保护因子.     

ALOX5启动子区基因多态性与儿童哮喘易感性及白三烯受体拮抗剂药效关系研究

目的观察ALOX5启动子区-1708 SNP及位于-176/-147的Sp1/Egr1结合位点重复序列多态性与儿童哮喘易感性、临床特征及白三烯受体拮抗剂(LTRA)药效的关系。方法选取2016年10月至2018年1月沈阳军区总医院儿科243例哮喘患儿为病例组,以同期体检的228例非哮喘儿童为对照组,应用聚合酶链反应(PCRs)、测序法对纳入对象ALOX5-1708及Sp1/Egr1结合位点基因分型,收集各项临床资料并予抗哮喘治疗,分析基因多态性与临床特征及LTRA药效关系。结果 (1)病例组Sp1/Egr1结合位点重复序列非5/5基因型频率明显高于对照组(OR=1.485,95%CI=1.018-2.167,χ2=4.225,P=0.040)。(2)中重度组G/A+A/A型及G/A型频率均高于轻度组(χ2=4.832、4.565,P=0.028、0.033),中重度组4/6型频率低于5/5型,而5/6型频率则高于5/5型(χ2=3.643、3.888,P=0.056、0.049)。结论 ALOX5 Sp1/Egr1结合位点重复序列多态性可能与儿童哮喘发病及严重程度、过敏及其家族史、LTRA效果有关;ALOX5-1708位点多态性可能与哮喘严重程度、肺功能指标及LTRA效果有关。     

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.     

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.     

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.