肺炎支原体肺炎及支气管哮喘HLA-DRB1基因位点频率研究

为探讨肺炎支原体（MP）肺炎的免疫致病机理及其与支气管哮喘9简称哮喘）之间的关系。应用颗粒凝集法检测29例MP肺炎患儿，40例哮喘患儿及92例正常对照组的血清MP特异性IgM抗体，PCR-SSOP法标记HLA-DRB1等痊基因位点。结果显示MP肺炎组，哮喘组的DRB1*08基因频率明显低于正常对照组（P=0.035)。但MP肺炎组与哮喘组之间差异无显著性，哮喘组中除DRB*08外，DRB1*02基因出现频率亦较正常人显著降低（P=0.041)；各组间HLA-DRB1*04，07，09，10，11，12基因频率虽有所变化，但均无统计学差异。提示MP肺炎与哮喘有着极为相似的遗传易感性。     

反复呼吸道感染患儿HLA-DRR1等位基因分析

目的 探讨HLA-DRB1基因多态性与反复呼吸道感染(RRI)的遗传关联性.方法 采用序列特异性引物-聚合酶链反应(SSP/PCR)技术对43例RRI小儿和41例健康小儿HLA-DRB1的19个等位基因进行分析,计算各个位点的基因分布频率和相对危险性RR值;并进行卡方检验,筛选有意义基因.结果 RRI患儿HLA-DRB1*9和HLA-DRB1*12的分布频率明显高于健康儿童,HLA-DRB1*7的分布频率明显低于健康儿童.观察组与对照组比较P＜0.05,差异有显著性,其它各位点差异无显著性.疾病组与正常组之间进行逐个等位基因的比较,以相对危险性RR值计算,HLA-DRB1*9的RR值为3.95,HLA-DRB1*12的RR值为3.16.HLADRB1*7的RR值为0.30.结论 HLA-DRB1*9和HLA-DRB1*12可能是RRI小儿的易感基因.HLA-DRB1*7可能是RRI小儿的保护基因.     

HLA-DRB1等位基因在幽门螺杆菌感染及免疫性血小板减少症患儿中的表达

目的　通过对幽门螺杆菌（Helicobacter pylori,HP）感染、免疫性血小板减少症（immune thrombocytopenia,ITP）、ITP合并HP感染患儿及健康儿童进行HLA-DRB1*03、*04、*07、*11、*14等位基因检测,探究HP感染及ITP的易感性基因及保护性基因。方法　收集北京儿童医院2014年5月至2015年1月HP感染患儿、ITP患儿、HP感染合并患儿及健康儿童的全血标本,提取全血DNA,应用PCR-SSP方法检测四组患儿HLA-DRB1*03、*04、*07、*11、*14等位基因表达频率,对比不同性别、不同组别之间基因表达频率的差异性。结果　选取的136例汉族儿童中,检测的5种HLA-DRB1等位基因分布频率分别为HLA-DRB1*04（21.32%）、HLA-DRB1*07（19.12%）、HLA-DRB1*14（15.44%）、HLA-DRB1*11（11.76%）、HLA-DRB1*03（8.82%）。分别比较以上5种等位基因在男女性别间的频率表达,差异无统计学意义;在比较HP组与健康对照组、ITP组与健康对照组、HP+ITP组与HP组、HP+ITP组与ITP组以上5种等位基因表达频率的差异性后发现,HLA-DRB1*07等位基因在ITP患儿和健康儿童的表达频率分别为：30.5%、9.7%（OR值=4.1,χ2=4.393,P=0.036）,差异具有统计学意义;HP感染合并ITP患儿携带HLA-DRB1*14等位基因的频率明显高于单一HP感染患儿（OR值=4.8,χ2=5.435,P=0.02）;在比较相同组别、不同性别间5种等位基因的分布频率后发现,HLA-DRB1*04等位基因在HP感染女童中的表达频率（40%）明显高于HP感染男童（4.8%）,经统计学分析,此等位基因在两组间的表达频率差异具有显著性（P=0.013）。结论　HLA-DRB1*07基因可能是ITP的易感性基因;HLA-DRB1*14（+）的HP感染患儿继发ITP的可能性更大,HLA-DRB1*04基因可能是女童感染HP的易感性基因。     

广西壮、汉族哮喘儿童人类白细胞抗原-B、-DR基因的多态性

目的 探讨广西壮、汉族人类白细胞抗原(HLA)-B、-DR位点的基因多态性与儿童哮喘发病的关联性.方法 将3代居住广西南宁地区无血缘关系的84例哮喘儿童(汉族57例,壮族27例)和168例无哮喘和特应性疾病的健康人(汉族83例,壮族85例)纳入研究.所有哮喘儿童应用强生法玛西亚系统检测其血清总IgE水平、10种吸入性变应原皮肤点刺试验和肺功能检测.利用基因芯片法检测HLA-B的40个和HLA-DR的26个等位基因.分别计算汉族和壮族人群中哮喘和健康对照组基因频率,进行x2检验,分别比较组间基因频率差异和危险性分析,计算基因与哮喘的关联强度比值比(OR值).结果 HLA-B位点共检出27个等位基因,HIA-DR检出21个等位基因.HLA-B46、HLA-DRB1～0.983)、7.885(0.896～69.399)和2.782(1.188～6.516),且HLA-DR B1*070X等位基因在本组壮族人群中未见出现.壮族人群中,HLA-B56、-861和-DRB1*1001等位基因在哮喘与健康对照组间有分布差异,哮喘与健康对照组比较有显著差异,组间HLA-B56经x2检验有统计学意义(x2=6.588 P<0.01),HLA-DRB1*1001经Fisher精确概率法检验有统计学意义(P=0.043);HLA-B56和HLA-DRB1*1001的OR值(95%CI)分别为9.432(1.713～51.932)和10.50(1.044～105.590).而HIA-B61等位基因在壮族哮喘患者中未见出现.结论 HLA-B和HLA-DR的基因多态性在壮、汉族间分布有差异;HLA-B56和HLA-DRB1*1001等位基因可能为壮族人群的哮喘易感基因;而汉族人群中HLA-DRB1*070X和HLA-DRB1*11XX等位基因是易感基因,HLA-B46等位基因可能为保护基因.*070X和HLA-DRB1*11XX等位基因仅在汉族的哮喘与健康人群分布有差异,哮喘与健康对照组比较有显著差异(Pa<0.05),OR值(95%CI)分别为0.388(0.153     

CD4^＋T淋巴细胞表面CD4^＋CD45RA和CD4^＋CD45RO在支气管哮喘患儿外周血中的表达

目的探讨CD4^＋CD45RA和CD4^＋CD45RO分子在支气管哮喘患儿中的表达及其意义。方法分别收集支气管哮喘发作期28例、支气管哮喘缓解期27例、健康对照儿童20例抗凝静脉血100μL，采用异硫氰酸荧光素（FITC）标记的抗CIM单抗、藻红蛋白（PE）标记的抗CD45RA单抗和PE-菁蓝色素荧光素（PE—Cy5）标记的抗CD45RO单抗，流式细胞仪检测各组儿童外周血CD4^＋T淋巴细胞表面CD45RA和CD45RO的表达。采用SPSS13．0软件进行统计学分析。结果与健康对照和支气管哮喘缓解组患儿比较，支气管哮喘发作组患儿CD4^＋CD45RA^＋T细胞明显减少（q=12．47，8，39Pa〈0．05），CD4^＋CD45RO^＋T细胞显著升高（q=9．50，8．30Pa〈0．05），CD4^＋CD45RA^＋／CD4^＋CD45RO^＋细胞比值显著降低（q=8．96，6．21P。〈0．05）；支气管哮喘缓解组患儿CD4^＋CD45RA^＋T细胞较健康对照组明显升高（q=3．08P〈0．05），CD4^＋CD45RO^＋T细胞及CD4^＋CD45RA^＋／CD4^＋CD45RO^＋细胞比值与健康对照组比较差异无显著性（q=0．45，2．02Pa〉0．05）。结论外周血CD4^＋CD45RA^＋和CD4^＋CD45RO^＋T淋巴细胞平衡失调可能参与支气管哮喘的发病。     

慢性咳嗽和喘息性疾病支气管肺泡灌洗液成分分析

目的 分析慢性咳嗽及喘息性疾病患儿支气管肺泡灌洗液成分。方法 应用免疫组化及ELISA方法，对哮喘（13例）、慢性咳嗽（10例）、婴幼儿喘鸣（8例）患儿和对照组（8例）共39例的支气管肺泡灌洗液进行细胞学分析及上清液IL－5浓度测定。结果 哮喘患儿支气管肺泡灌洗液嗜酸性粒细胞为3．0％（0．7％－8．8％），上皮细胞为3．0％（0．7％－12．0％），IL－5为1．7ng/L(0－16.0ng/L)，与慢性咳嗽组及婴幼儿喘鸣组相比，差异有非常显著意义（P＜0．01）；2例慢性咳嗽及3例婴幼喘鸣儿哮酸性粒细胞亦有异常增多，与组内其他必相比差异有显著意义；婴幼儿喘鸣组中性粒细胞明显增多。结论 哮喘患儿支气管肺泡灌洗液以嗜酸性粒细胞和上皮细胞明显增多为其特征性改变；慢性咳嗽患儿中有嗜酸性粒细胞异常增多者，应注意与哮喘鉴别；婴幼儿喘鸣者以中性粒细胞增多为著，抗哮喘治疗应慎重。     

信号转导子及转录激活因子2基因rs2066807C→G多态性与支气管哮喘的相关性

目的探讨信号转导子及转录激活因子2(STAT2)基因单核苷酸多态位点rs2066807C→G多态性与潍坊地区汉族人群儿童哮喘的关系。方法应用PCR-限制性内切酶多型性法,对92例支气管哮喘患儿(哮喘组)和98例健康儿童(健康对照组)STAT2基因rs2066807C→G多态性进行检测,计算基因型和等位基因频率,组间比较采用χ2检验。相关疾病的基因型风险率以参与风险及比值比(OR)表示,95%可信区间(95%CI)计算采用Miettinen法。结果STAT2基因rs2066807C→G多态位点CC、CG、GG基因型频率,哮喘组患儿分别为0、3.4%、96.6%,健康对照组分别为0、6.1%、93.9%;C和G等位基因频率,哮喘组为1.6%和98.4%,健康对照组为3.1%和96.9%。哮喘组STAT2基因各基因型和等位基因频率和健康照组比较差异均无统计学意义(Pa>0.05)。携带CG基因型和C等位基因的儿童发生支气管哮喘的相对风险OR值分别为0.34(95%CI:0.05～4.96)和0.33(95%CI:0.05～4.93)(Pa>0.05)。结论STAT2基因rs2066807C→G多态性与潍坊地区儿童支...     

肾病综合征患儿系膜增殖性肾炎人类白细胞抗原DR基因频率

利用寡核苷酸探针杂交技术及聚合酶链反应技术，检测了临床表现为肾病综合征的36例患儿人类白细胞抗原（HLA）－DR基因频率的分布；其中9例为IgA肾病，27例为非IgA系膜增殖性肾炎。分别与255例正常汉族人HLA－DR基因频率进行比较，发现IgA肾病患儿HLA－DR4基因频率明显高于正常人［DR4：19．4％vs9．0％，Pc＜0．05，相对危险系数（OR）=2．98］；而非IgA系膜增殖性肾炎HLA－DR12（5）基因频率明显高于正常人[DR12（5）：13．9％vs3．9％，Pc＜0．01，OR=4．52]。提示HLA－DR4、HLA－DR12（5）分别与临床表现为肾病综合征的儿童IgA肾病和非IgA系膜增殖性肾炎具有明显相关性。     

肺炎支原体感染与儿童哮喘关系的研究

目的探讨肺炎支原体感染与儿童哮喘发病的关系。方法支气管哮喘患儿362例，肺炎患儿288例，正常对照组30例，分别采用颗粒凝集法检测血清肺炎支原体IgM（MP—IgM）抗体；同时采用同位素放射免疫法测定哮喘患儿血清总IgE。结果（1）支气管哮喘患儿MP-IgM阳性率49．45％，显著高于肺炎患儿MP—IgM阳性率39．24％，上述两组均显著高于正常对照组6．67％；（2）在各年龄组支气管哮喘患儿MP—IgM阳性率比较中，发现学龄期儿童MP-IgM阳性率最高；（3）MP—IgM阳性的支气管哮喘患儿血清总IgE水平明显高于MP-IgM阴性哮喘患儿的血清总IgE。结论儿童肺炎支原体感染与儿童哮喘发病密切相关。     

幼年特发性关节炎患儿HLA-DRB1基因多态性分析

目的：研究广东地区汉族幼年特发性关节炎（JIA）患儿HLA-DRB1位点等位基因多态性分布特点。方法：采用序列特异性引物-聚合酶链反应(SSP-PCR)技术对94例JIA患儿和226例健康儿童HLA-DRB1的13个等位基因进行分析,并分析上述基因在各组中的分布。结果：JIA患儿HLA-DRB1*08(P=0.0014,OR=2.26)的分布频率明显高于健康儿童,HLA-DRB1*12（P=0.032,OR=0.55）的分布频率明显低于健康儿童。在JIA全身型及多关节型中HLA-DRB1*08明显增高,而HLA-DRB1*15在JIA全身型及少关节型中明显降低,观察组与对照组比较P<0.05,差异有统计学意义,其他各位点差异无统计学意义。结论： HLA-DRB1*08可能是JIA小儿的易感基因。HLA-DRB1*12可能是JIA小儿的保护基因,其中HLA-DRB1*08是全身型及多关节型的易感基因,而HLA-DRB1*15与全身型及少关节型保护基因密切相关。［中国当代儿科杂志,2010,12（5）：333-337］     

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   

�¶�֢��ϵ�ϰ���ע��ȱ�ݶද�ϰ������ڵ�ת��

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.

---

---

Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.