先天性心脏病合并心功能不全患者心肌AMP分解途径的探讨

目的: 观察先心病合并慢性心功能不全患者心肌中一磷酸腺苷(AMP)代谢途径的变化。方法: 随机选取手术治疗的先心病患者27例,年龄(11.9±13.6)岁,男性15例,女性12例。按纽约心功能分级(NYHA)分3组,A组为心功能正常组(Ⅰ级),B组为心功能轻度受损组(Ⅱ级),C组为心功能重度受损组(Ⅲ-Ⅳ级)。手术中体外循环前剪取右心耳心肌,以高效液相色谱法测定心肌中AMP及其代谢产物腺苷(Ado)和次黄嘌呤核苷酸(IMP)的含量。同时观察左心室EF值与AMP及其代谢产物Ado和IMP含量、Ado和IMP比值变化,观察心内矫治手术后心衰等并发症。结果: 3组心肌AMP含量无显著差异,C组心肌Ado含量明显低于B组,IMP含量高于B组。B组和C组IMP与Ado含量的比值(K常数)增高。术前左心室EF值与K常数呈负相关。K常数值明显增高者,心内矫治术后发生心衰较多。结论: 随着先心病患者心功能的降低,心肌AMP分解偏向于生成次黄嘌呤核苷酸。术前左心室EF降低与AMP分解代谢异常有关,应注意术后心衰的发生。     

Vascular endothelial growth factor in children with cyanotic and acyanotic and congenital heart disease

Introduction

Vascular endothelial growth factor is a potent stimulator of angiogenesis. Children with cyanotic congenital heart disease often experience the development of widespread formation of collateral blood vessels, which may represent a form of abnormal angiogenesis resulting in increased morbidity and mortality. We undertook the present study to determine whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor compared to children with acyanotic heart disease.

Material and methods

Serum was obtained from 35 children with cyanotic congenital heart disease and 30 children with acyanotic heart disease. Vascular endothelial growth factor levels were measured in the serum of these patients by sandwich enzyme immunoassay.

Results

Vascular endothelial growth factor was significantly elevated in children with cyanotic congenital heart disease compared to children with acyanotic heart disease (150.3 ±48.1 vs. 85.4 ±18.7 pg/ml, respectively, p < 0.001). In the cyanotic group, oxygen saturation (SaO₂) was negatively correlated with VEGF (r=–0.631, p < 0.001) while haemoglobin was positively correlated (r=0.781, p = 0.007). No significant correlations were found in the acyanotic group.

Conclusions

Children with cyanotic congenital heart disease have elevated systemic levels of vascular endothelial growth factor directly related to the degree of cyanosis (SaO₂ and haemoglobin levels). These findings suggest that the widespread formation of collateral vessels in these children may be mediated by vascular endothelial growth factor.     

Epidemiology and clinical features of community-acquired,healthcare-associated and nosocomial bloodstream infections in tertiary-care and community hospitals

Classification of bloodstream infections (BSIs) as community-acquired (CA), healthcare-associated (HCA) and hospital-acquired (HA) has been proposed. The epidemiology and clinical features of BSI according to that classification in tertiary-care (TH) and community (CH) hospitals were investigated in a prospective cohort of 821 BSI episodes from 15 hospitals (ten TH and five CH hospitals) in Andalucía, Spain. Eighteen percent were CA, 24% were HCA and 58% were HA. The incidence of CA and HCA BSI was higher in CH than in TH (CA: 3.9 episodes per 1000 admissions vs. 2.2, p <0.01; HCA: 5.0 vs. 2.9, p <0.01), whereas the incidence of HA BSI was lower (7.7 vs. 8.7, p <0.01). In CA and HCA BSI, the respiratory tract was more frequently the source in CH than in TH (CA: 30% vs. 15%; HCA: 20% vs. 9%, p ≤0.03). In HCA BSI, chronic renal insufficiency and tunnelled catheters were less frequent in CH than in TH (11% vs. 26% and 7% vs. 19%, p ≤0.03), although chronic ulcers were more frequent (22% vs. 8%, p 0.008). BSIs as a result of methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa were very rare in CA episodes, although extended-spectrum β-lactamase-producing Escherichia coli (ESBLEC) caused a similar proportion of all BSIs in CA, HCA and HA episodes. Multivariate analysis revealed no significant difference in mortality rates in CH and TH. HCA infections should be considered as a separate class of BSI in both TH and CH, although differences between hospitals must be considered. CA BSIs were not caused by multidrug-resistant pathogens, except for ESBLEC.     

Syk-coupled C-type lectin receptors that mediate cellular activation via single tyrosine based activation motifs

Summary: Different dendritic cell (DC) subsets have distinct specialized functions contributed in part by their differential expression of pattern recognition receptors (PRRs). C-type lectin receptors (CLRs) are a group of PRRs expressed by DCs and other myeloid cells that can recognize endogenous ligands as well as a wide range of exogenous structures present on pathogens. Dual roles in homeostasis and immunity have been demonstrated for some members of this receptor family. Largely due to their endocytic ability and subset specific expression, DC-expressed CLRs have been the focus of significant antigen-targeting studies. A number of CLRs function on the basis of signaling via association with immunoreceptor tyrosine-based activation motif (ITAM)-containing adapter proteins. Others contain ITAM-related motifs or immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails. Here we review CLRs that induce intracellular signaling via a single tyrosine-based ITAM-like motif and highlight their relevance in terms of DC function.     

Non‐classic cystic fibrosis associated with D1152H CFTR mutation

Burgel P‐R, Fajac I, Hubert D, Grenet D, Stremler N, Roussey M, Siret D, Languepin J, Mely L, Fanton A, Labbé A, Domblides P, Vic P, Dagorne M, Reynaud‐Gaubert M, Counil F, Varaigne F, Bienvenu T, Bellis G, Dusser D. Non‐classic cystic fibrosis associated with D1152H CFTR mutation. Background: Limited knowledge exists on phenotypes associated with the D1152H cystic fibrosis transmembrane conductance regulator (CFTR) mutation. Methods: Subjects with a D1152H allele in trans with another CFTR mutation were identified using the French Cystic Fibrosis Registry. Phenotypic characteristics were compared with those of pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) subjects in the Registry (CF cohort). Results: Forty‐two subjects with D1152H alleles were identified. Features leading to diagnosis included chronic sinopulmonary disease (n = 25), congenital absence of the vas deferens (n = 11), systematic neonatal screening (n = 4), and genetic counseling (n = 2). Median age at diagnosis was 33 [interquartile range (IQR, 24–41)] years in D1152H subjects. Median sweat chloride concentrations were 43.5 (39–63) mmol/l in D1152H subjects and were markedly lower than in PI and PS CF subjects (p < 0.05). Bronchiectasis was present in 67% of D1152H subjects, but Pseudomonas aeruginosa colonization and pancreatic insufficiency were present in <30% of subjects. Estimated rates of decline in forced expiratory volume in 1 s (FEV₁) were lower in D1152H subjects vs PI CF subjects (p < 0.05). None of the D1152H subjects identified since 1999 had died or required lung transplantation. Conclusions: When present in trans with a CF‐causing mutation, D1152H causes significant pulmonary disease, but all subjects had prolonged survival.     

先天性厚甲症Ⅰ型一家系角蛋白6A基因突变研究

目的 研究1个先天性厚甲症Ⅰ型(pachyonychia congenital type Ⅰ,PC-Ⅰ)家系中的角蛋白6A(keratin 6A,K6A)基因突变情况.方法 收集1个先天性厚甲症Ⅰ型家系,并提取该家系中2例患者及3名表型正常者和100名无亲缘关系健康个体的外周血标本,通过聚合酶链反应结合其产物DNA直接测序的方法 ,检测K6A基因的突变情况.结果 该家系中患者存在K6A基因上第521位碱基胸腺嘧啶(T)转化成胞嘧啶(C),使得K6A基因的第1外显子174位密码子由TTT突变成TCT,导致所编码的苯丙氨酸被丝氨酸取代,而该家系的正常人及无关健康个体对照不存在此突变.结论 该PC-Ⅰ家系中患者的表现型是K6A基因的错义突变(521 T→C)引起.     

先天性室间隔缺损中的一个GATA4基因新突变

目的 研究GATA4基因新突变导致先天性室间隔缺损(ventricular septal defect,VSD)的分子机制.方法 收集185例先天性VSD患者的临床资料和血标本,以200名健康者为对照.应用PCR扩增GATA4基因的全部外显子,采用双脱氧核苷链末端合成终止法对全部扩增片段进行测序以识别基因突变.克隆GATA4基因,通过定位诱变获得相应的突变体,应用脂质体将GATA4基因重组表达质粒及心房利钠肽基因启动子启动绿色荧光蛋白表达的报告载体转染HeLa细胞,应用逆转录-PCR研究GATA4基因突变对其编码的转录因子的活性的影响.结果 在1例VSD患者的GATA4基因发现1个新的杂合错义突变c.191G＞A,即第64位的密码子由GGA变为GAA,导致第64位的甘氨酸变为谷氨酸,即G64E突变.细胞表达分析显示GATA4突变G64E使转录因子的活性降低.结论 在先天性VSD患者发现GATA4新突变G64E,该突变可能通过抑制转录因子的活性而参与先天性VSD.     

先天性髋脱位与HOXB9基因或COL1A1基因传递不平衡研究

目的 探讨先天性髋脱位(congenital dislocation of the hip，CDH)与HOXB9基因或COL1Al基因是否存在相关性。方法 在胚胎肢体发育调控相关的HOXB9基因和COL1A1基因共同所在的染色体区域17q21内选择微卫星DNA标记D17S1820，应用聚合醇链反应及变性聚丙烯酰胺凝胶电泳技术，对101个CDH核心家系的303名成员进行基因型分析，并进行传递不平衡检验(transmission disequilibrium test,TDT)。结果 在D17S1820多态性标记位点上共检测到12个等位基因。TDT分析显示，CDH与D17S1820遗传标记位点的第4个等位基因存在传递不平衡(x^2＝6．025，P＝0．014)。结论 CDH与HOXB9基因和COLlAl基因共同所在的染色体区域17q21有关联，HOXB9基因和(或)COLlAl基因可能是CDH的易感基因。     

感染细胞中SARS相关病毒的形态学观察

目的 用电子显微镜观察严重急性呼吸综合征(SARS)患者标本感染细胞,为SARS病原体的分离鉴定提供形态学资料。方法 以北京和广州地区SARS病例尸检肺组织和鼻咽拭子标本感染Vero E6细胞,通过对培养上清液和病变细胞超薄切片观察,了解病毒的大小、形态、在感染细胞中的分布和装配情况,初步判定病毒的分类。结果 在3价标本感染的细胞培养液和病变细胞中均查见病毒,病毒颗粒多呈圆形或椭圆形,大小80～120nm,外周有冠状排列的纤突。在广州肺组织标本感染的细胞中还查见大量的短杆状和少量肾形、不规则形的病毒颗粒,大小100～200nm×60～90nm,其他标本感染细胞中这种形态的病毒颗粒较少见。切片中见病毒主要分布在细胞质的内质网池、高尔基体、空泡、包涵体内和细胞外,呈空心和实心两种形式。包涵体内病毒颗粒排列紧密,其大小、形态不一。病毒以胞饮或膜融合形式进入细胞,以出芽方式增殖。结论 电镜查见SARS病例标本中分离出典型的圆形或椭圆形的冠状病毒,与文献报道的SARS相关新型冠状病毒相符。同时我们也发现了另一种以短杆状为主,偶见梨形、肾形、多形性的病毒颗粒,它们在SARS研究中的意义有待进一步探讨。