烟碱样乙酰胆碱受体α7在支气管哮喘患儿CD4+T淋巴细胞上的表达

目的探讨哮喘患儿血CD4＋T淋巴细胞表达烟碱样乙酰胆碱受体α7（nAChRα7）与相应的细胞培养液IL-4、干扰素-γ（IFN-γ）水平的关系,分析nAChRα7在哮喘发病过程中的临床意义。方法哮喘患儿30例（哮喘组）与健康儿童20例（健康对照组）,分别抽取静脉血8mL,分离外周血淋巴细胞,并分别加入100μmol/L烟碱、1.0mg/Lα-银环蛇毒（α-BTX）,另设空白对照,恒温孵育24h后提取其淋巴细胞,并收取培养液置-20℃冰箱保存。用三色流式细胞仪检测各组淋巴细胞CD3^＋/CD4^＋/nAChRα7表达。ELISA法检测其淋巴细胞培养液中IFN-γ、IL-4水平。结果哮喘组患儿血CD3^＋/CD4^＋/nAChRα7表达较健康对照组儿童明显增高（P〈0.05）。烟碱刺激24h后哮喘组、健康对照组外周血CD3^＋/CD4^＋/nAChRα7的表达均较空白对照明显增加（Pa〈0.01）;且烟碱刺激24h后哮喘组较健康对照组表达显著增加（P〈0.05）。α-BTX刺激24h后外周血CD3^＋/CD4^＋/nAChRα7表达降低,但无统计学意义（Pa〉0.05）。哮喘组培养液中IL-4水平较健康对照组增加,IFN-γ水平较健康对照组减低。烟碱刺激24h后IL-4水平较空白对照增高（P〈0.01）,IFN-γ水平较空白对照明显减低（P〈0.05）。α-BTX刺激24h后IL-4、IFN-γ水平均无明显变化（Pa〉0.05）。外周血CD4＋T淋巴细胞nAChRα7表达与淋巴细胞培养液IL-4水平呈正相关（r=0.517P〈0.05）,与IFN-γ水平呈负相关（r=-0.288P〈0.05）。结论哮喘患儿血CD4＋T淋巴细胞表面的nAChRα7表达增加,nAChRα7表达影响培养液IL-4、IFN-γ水平和Th1/Th2平衡,是影响哮喘的发病的重要因子。     

系统性红斑狼疮患儿PD-1分子的表达

目的 研究PD-1分子的表达与系统性红斑狼疮（SLE）的发病机制及病情的关系。方法 应用流式细胞仪检测各期SLE患儿（活动期、缓解期）外周血CD3^＋、CD4^＋、CD8^＋T细胞上PD-1分子的表达。结果 在各期SLE患儿中外周血CD3^＋、CD4^＋、CD8^＋淋巴细胞上PD-1分子的表达均明显高于正常对照（P〈0.05）。结论 在系统性红斑狼疮患儿外周血淋巴细胞上PD-1分子表达明显高于正常,各组SLE患儿存在B淋巴细胞的异常增殖,推测 PD-1通路在SLE的免疫病理中发挥重要作用。     

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。     

条件免疫对胶原性关节炎大鼠烟碱样乙酰胆碱受体及胆碱乙酰转移酶表达的影响

目的建立条件免疫反应(CIR)模型,研究CIR状态下胶原性关节炎(CIA)大鼠烟碱样乙酰胆碱受体α7亚单位(nAChRα7)、胆碱乙酰转移酶(ChAT)蛋白和mRNA表达,探讨CIR可能的胆碱能通路作用机制。方法将大鼠分为健康对照组和CIA模型组,模型组大鼠分为5组:CIR组;甲氨蝶呤(MTX) 泼尼松(Pred)治疗组;MTX Pred治疗减量组;单纯闻樟脑气味组;空白对照组。用免疫组织化学方法和RT-PCR方法检测各组大鼠关节滑膜nAChRα7、ChAT蛋白和mRNA表达。结果免疫组织化学和RT-PCR均显示CIR组关节滑膜nAChRα7、ChAT蛋白和mRNA的表达明显均高于空白对照组(P均<0.01);空白对照组大鼠表达nAChRα7、ChAT明显低于健康对照组和CIR(P均<0.01),而MTX Pred组、MTX Pred减量组、单纯闻樟脑气味组均与空白对照组差异无显著性(P均>0.05)。结论CIR状态下nAChRα7、ChAT mRNA和蛋白表达水平增高,表明胆碱能抗炎通路在CIR治疗胶原性关节炎大鼠的作用机制中起重要作用。     

全身型幼年特发性关节炎患儿血淋巴细胞程序凋亡分子表达的意义

目的探讨程序凋亡分子（PD-1）在全身型幼年特发性关节炎（SoJIA）发病机制中的作用。方法SoJIA组24例和健康对照组39例。应用流式细胞术测定二组T、B淋巴细胞亚群百分比及PD-1在CD^3＋T、CD^4＋T、CD^3＋CD4-T、CD19＋B淋巴细胞上表达。结果SoJIA患儿CD^3＋T、CD^3＋CD4-T及CD19＋B淋巴细胞亚群百分比显著高于健康对照组（t=4.345,6.132,4.019 Pa〈0.05）,PD-1在上述淋巴细胞亚群上表达均显著高于健康对照组（t=16.238,17.536,15.561,6.301 Pa〈0.05）;治疗后SoJIA患儿PD-1在CD19^＋B淋巴细胞上表达显著低于治疗前（t=5.986 P〈0.05）,且PD-1在CD19^＋B淋巴细胞上表达与ESR呈正相关（r=0.520 P〈0.05）。结论SoJIA患儿可能存在PD-1分子功能区域结构异常或PD-1/PD-L通路功能障碍,或由于正性刺激信号过强超过负性抑制信号抑制免疫反应作用,从而导致疾病发生。     

幼年特发性关节炎患儿CD4+CD25high调节性T细胞检测的意义

目的探讨CD4^＋ CD25^high调节性T细胞在幼年特发性关节炎（JIA）发病机制中的作用。方法利用流式细胞术检测JIA患儿外周血和关节液中T细胞表面CD4和CD25表达,并利用胞内染色技术检测细胞内转录因子FoxP3。同时检测年龄和性别相匹配的7例健康体检儿童外周血作为正常对照。结果JIA患儿关节液中高表达CD25的CD4^＋ T细胞（CD4^＋CD25^high）明显多于JIA和正常人外周血,而JIA外周血中数量又少于正常人外周血。CD4^＋ CD25^highT细胞表达高水平的FoxP3。结论JIA患儿关节局部天然调节性T细胞增多,可能与其发病机制有关。     

哮喘患儿CD4+CD25+T细胞FoxP3表达的意义

目的研究表达FoxP3的CD4^＋ CD25^＋调节性T细胞在哮喘儿童外周血中的比例改变,探讨其在发病机制中的意义。方法采用细胞内染色的流式细胞术及定量PCR方法,分别在蛋白质和mRNA水平检测哮喘患儿外周血FoxP3表达,并与健康对照组进行比较。结果哮喘患儿CD4和CD25双阳性细胞所占比例与健康对照组比较无明显差异,而CD4^＋ CD25^high和CD4^＋ CD25^＋ FoxP3＋细胞明显低于对照组（Pa〈0.05）。FoxP3 mRNA表达水平与蛋白质表达水平变化一致。结论哮喘患儿CD4^＋ CD25^＋ FoxP3＋调节性T细胞明显减少,可能与哮喘的发病机制有关。     

CTLA-4/CD28的表达与儿童急性淋巴细胞白血病临床预后的关系

目的探讨外周血T淋巴细胞表面CTLA-4/CD28的表达与儿童急性淋巴细胞白血病(ALL)发病及治疗转归的相关性。方法采用流式细胞术(FCM)分别检测21例B细胞型ALL患儿初发且未治疗前、经VDLD方案治疗达到完全缓解并持续缓解予CAT巩固停药2~3周后外周血T淋巴细胞表面CTLA-4、CD28的表达。结果(1)治疗前:ALL患儿外周血CD4~+T、CD8~+T淋巴细胞CTLA-4表达显著高于正常水平(P<0.01),CD28表达显著低于正常水平(P<0.01);(2)治疗后:ALL患儿在达到完全缓解时外周血CD4~+T、CD8~+T淋巴细胞CTLA-4的表达显著低于治疗前(P<0.01),与正常对照组比较差异无显著性(P>0.05),CD28的表达显著高于治疗前(P<0.01),与正常对照组比较差异无显著性(P>0.05)。结论(1)T淋巴细胞不能被充分活化,对肿瘤的免疫监视与清除功能降低,可能是ALL的发病因素之一;(2)化疗过程中注重调节T淋巴细胞的免疫功能、刺激T淋巴细胞正常活化可能有助于提高ALL的治疗缓解率。     

重症感染患儿胸腺萎缩与免疫的关系及影响因素

目的探讨小儿重症感染时胸腺萎缩与免疫的关系及影响因素。方法回顾性分析尸体解剖证实76例重症感染患儿和48例非感染患儿胸腺重量、细胞免疫指标及抗生素和地塞米松使用情况。结果重症感染患儿胸腺重量明显减轻,体积缩小,与非感染患儿胸腺比较有显著性差异（P〈0.01）;使用较大剂量地塞米松超过7d者其胸腺重量较3d者明显减轻,有显著性差异（P〈0.05）;重症感染患儿E-花环形成率、淋巴细胞转化率和T细胞亚群CD3^＋、CD4^＋、CD8^＋及CD4^＋/CD8^＋表达均明显低于非感染患儿（Pa〈0.05）;感染患儿病程与其胸腺重量呈明显负相关（r=-0.638P〈0.01）。结论胸腺萎缩可能是感染、蛋白质和热卡供给不足及滥用糖皮质激素等共同作用结果,并导致免疫功能低下。动态监测重症感染患儿免疫指标对临床诊治有重要指导意义。     

人脐血T、B淋巴细胞和NK细胞的免疫学表达特性

目的 探讨人脐血T、B淋巴细胞和NK细胞，以及T／NK细胞杀伤性抑制性受体（KIR）表达的免疫学特性及其意义。方法 应用流式细胞仪检测26例正常新生儿脐血的T、B淋巴细胞和NK细胞抗原标记，包括CD45RA、CD45RO、CD69、CD25、CD40L、CD40、CD10、CD20和CD16等抗原的表达，以及脐血T／NK细胞上KIR分子（CD158a和CD158b抗原）的表达，并与正常儿童外周血比较。结果 脐血T淋巴细胞中CD45RA^ 细胞表达高于外周血（P＜0．01），CD45RO^ 则明显低于外周血（P＜0．01）；脐血T细胞CD69表达极低；CD25在CD8^ 细胞亚群中几乎不表达；CD40L在脐血T细胞中表达低于外周血（P＜0．05）。脐血B淋巴细胞中不成熟亚群CD10^ ／CD19^ 比例增高，成熟B细胞表型CD19、CD20、CD40等抗原均明显高于正常外周血（P＜0．01）。脐血中T淋巴细胞和NK细胞均存在KIR分子表达；脐血和外周血中T淋巴细胞CD158分子表达低于NK细胞（P＜0．01），脐血T淋巴细胞亚群中CD158分子表达低于正常外周血；CD158几乎不表达于CD4^ T细胞，主要表达于CD8^ T细胞，且以CD158a^ 为主；脐血中NK细胞CD158分子表达高于T淋巴细胞（P＜0．05），但明显低于外周血NK细胞KIR的表达（P＜0．01）。结论 脐血T淋巴细胞包括原始和早期T细胞以及T细胞受体表达障碍，导致脐血T淋巴细胞免疫功能不成熟，可能是脐血移植（UCBT）后移植物抗宿主病（GVHD）发生率低和程度轻的重要原因之一。脐血B淋巴细胞免疫应答障碍可能缘于T淋巴细胞表型或功能的障碍。脐血T／NK细胞KIR的表达特性提示，KIR可能与UCBT中GVHD和移植物抗白血病（GVL）效应有关。     

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.     

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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.     

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   

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.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

How well are we doing? – Metabolic control in patients with diabetes

OBJECTIVE: To compare the present level of metabolic control in children and adolescents with insulin-dependent diabetes mellitus (IDDM) attending Brisbane paediatric diabetes clinics with published overseas data. METHODOLOGY: Blood HbA1c concentrations, population characteristics, current treatment practices and short-term complications were recorded in all patients, aged 19 years and under, attending the diabetes clinics of the two Brisbane Children's Hospitals or the private practice of one of the authors (MJT) in the first quarter of 1998. RESULTS: Two hundred and sixty-eight patients were assessed (M/F 142/126). Ages ranged from 1 to 19 years (mean 11. 2 years); duration of IDDM was 0-16 years (mean 4.4 years); and 141 (53%) were pubertal. Of those aged less than 13 years, only 4% had more than two injections daily. Insulin doses (U/kg/day) rose with increasing age. Larger doses were required in regimens involving more than two injections per day than those involving one to two injections per day. Ketoacidosis or severe hypoglycaemia in the last 3 months were reported in eight (2.7%) and 17 (6.3%) of patients, respectively. Mean HbA1c (+/- SD) was 8.6 +/- 1.4% (range 5.2-14.0%), with 33% of children having a HbA1c concentration < 8%. HbA1c concentrations were significantly related (P < 0.05) to insulin dose and to duration of diabetes, but not to severe hypoglycaemia, ketoacidosis, age, frequency of injections, or number of clinic visits per year. Mean HbA1c concentration was significantly higher (P < 0.05) in those children in puberty (8.7 +/- 1.5%) than in those not in puberty (8.5 +/- 1.2%). CONCLUSION: Only 33% of patients had a HbA1C concentration less than 8% and 6.3% had a severe hypoglycaemic episode in the 3 months. These results are similar to published overseas data.