Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

IL-1Ra和IL-10真核表达质粒载体的构建及其表达检测

目的:构建人IL-1Ra和人IL-10真核表达质粒载体并检测其表达。方法:用双酶切方法切取PCDI-IL-1Ra和PCDI-IL-10质粒中包含人IL-1Ra和人IL-10 CDS全长序列的cD-NA片段,并分别连接到真核表达质粒pcDNA3.1上,然后用壳聚糖转染上述质粒到原代软骨细胞,RT-PCR检测其mRNA水平的表达。结果:成功将人IL-1Ra和IL-10 CDS全长序列的cDNA片段克隆到真核表达载体,mRNA水平检测到目的基因的表达明显提高。结论:真核表达质粒可以用于外源基因的原代软骨细胞导入和表达,为进一步的基因治疗研究提供依据。     

北京地区rt-PA静脉溶栓治疗超早期脑梗死患者临床分析

目的分析北京地区12所医院202例超早期脑梗死患者经不同剂量重组组织型纤溶酶原激活剂(rt- PA)静脉溶栓治疗后的疗效及其不良事件,探讨使用rt-PA的最佳剂量及其安全性与可行性。方法287例发病6h以内的脑梗死患者,男201例,女86例,年龄38～80岁,平均64岁。所有患者均伴有偏瘫,头颅CT未见出血及责任梗死灶,无溶栓禁忌证。202例接受rt-PA治疗,分为A组与B组,A组88例,给予rt-PA 0．9 mg/kg。B组114例,给予rt- PA0．6～0．8 mg/kg。C组(对照组)85例患者给予低分子右旋糖酐、复方丹参等治疗。分别比较治疗前与治疗后11d、21 d、90 d的美国国立卫生院神经功能缺损评分(NIHSS)、Barthel指数,并进行疗效评定。结果A组、B组分别与C组90 d的NIHSS评分、Barthel指数相比有显著差异。A组、B组及C组的基本痊愈及显著改善率分别为69%、77%及40%．A组、B组分别与C组脑出血的发生率为7．96%、4．38%及0%。症状性出血(4．55%、2．63%及0%),非症状性出血(2．63%、1．75%及0%)。结论超早期脑梗死静脉应用rt-PA溶栓治疗是安全有效的。不同剂量的rt-PA均减轻了脑梗死的致残率,但两组间无明显差异。中国人rt-PA溶栓治疗最佳剂量尚需要进一步进行大样本的前瞻性、多中心、随机对照研究．     

早期联用MEP和大剂量rhGH对严重烫伤大鼠肠源性感染的影响

目的探讨早期联用美罗培南(MEP)和大剂量重组人生长激素(rhGH)对严重烫伤免疫抑制大鼠肠源性感染的影响。方法Wistar大鼠54只随机分为对照组、烧伤组和治疗组(C1组、C2组、C3组),后两大组制成25%总体表面积(TBSA)Ⅲ°烫伤免疫抑制模型,伤后2h给予rhGH1.33IU/kg、MEP20mg/kg,伤后8、24h检测门静脉血清内毒素(LPS)、腔静脉血清肿瘤坏死因子-α(TNF-α)含量,肝功能变化和肠道细菌移位率。结果C3(MEP+rhGH治疗)组LPS和TNF-α含量均显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05),C3组未发现肠道细菌移位且肝功能检测指标显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05)。结论早期联用MEP和rhGH治疗严重烫伤免疫抑制大鼠能显著减轻或防止肠道细菌/内毒素移位,减少炎症介质释放,保护脏器功能。     

急性脑梗死超早期重组组织型纤溶酶原激活物溶栓治疗的临床研究

目的:探讨发病6h内急性脑梗死给予重组组织型纤溶酶原激活物(rt-PA)溶栓治疗的疗效及并发症,并分析预后相关因素。方法:共收集本院2001-2005年70例溶栓治疗的急性脑梗死病例,其中52例静脉溶栓,18例动脉溶栓,分析比较两组病例溶栓前后及3个月随访的ESS评分及Barthel指数结果;同时分析与预后相关的因素。结果:静脉和动脉溶栓组溶栓前及溶栓30min后ESS评分及Barthel指数迅速增加,溶栓前后分值有显著差异。1个月内颅内出血率为5.77%(静脉组)和16.67%(动脉组)。3个月时ESS评分及Barthel指数较溶栓后30min的评分有显著改善。结论:6h内动脉、静脉溶栓治疗均安全有效。     

人睫状神经营养因子结构和功能的研究

制备高活性的重组人睫状神经营养因子，并研究其生物学功能。方法：应用大肠杆菌表达ｈＣＮＴＦ，用片段插入和法研究其结构与功能关系；切断大鼠骨神经，局部及皮下给予ＣＮＴＦ，应用辣根过氧化物酶逆行追踪技术显示再生轴突通过修复部位的胞体。结果；ｈＣＮＴＦ分子中α－螺旋结构的维持对其生物活性十分重要Ｃ端松散地其生物活性贡献不大，Ｄ螺旋中后段可能与生物活性有密切关系；     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

IgE-mediated anaphylactic reaction to purified and recombinant factor VIII in a patient with severe haemophilia A

We report a 51-year-old patient with severe haemophilia A developing a severe life-threatening anaphylactic reaction to recombinant factor VIII (rFVIII). Anaphylactic reactions are a rare but well-known side effect of FVIII products. The nature of these reactions could not be clarified as previous studies failed to demonstrate a specific IgE response. Here, we could prove a grade 3 anaphlyactic reaction as an IgE-mediated response to rFVIII for the first time by Western blotting.     

肝硬化大鼠肝部分切除术后肝再生的干预研究

目的　以肝硬化大鼠为动物模型 ,研究药物对肝硬化大鼠肝部分切除术后肝再生的影响。方法　取健康的Wistar雄性大鼠 6 4只 ,以 6 0 ?l4油溶液 0 .3ml/ 10 0 g皮下注射 ,同时饮用 5 %酒精溶液 ,4 5d后制成肝硬化动物模型。模型大鼠随机分为 4组 ,16只 /组。全麻下均行左、中叶肝切除术。术后各组按以下方案处理 :A组 (对照组 )注射生理盐水 1mg/ (kg·d) ,B组为泮托拉唑组 ,注射 0 .2mg/ (kg·d) ,C组为重组人生长激素组 ,注射 0 .5U/ (kg·d) ,D组为两药合用组 ,同时给予泮托拉唑注射 0 .2mg/ (kg·d) ,重组人生长激素注射 0 .5U/ (kg·d) ) ,连续给药 1周。抽取静脉血样 ,取肝脏组织 ,检测肝功能、有丝分裂指数 (MI)、增殖细胞核抗原 (PCNA)、细胞核DNA含量。结果　泮托拉唑组、重组人生长激素组、两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于对照组 (P <0 .0 5 ) ,两药合用组MI、PCNA阳性染色细胞量、细胞核DNA含量均高于泮托拉唑组、重组人生长激素组 (P <0 .0 5 ) ,但各组间肝功能变化无明显差异。结论　泮托拉唑组及重组人生长激素均对肝硬化大鼠肝部分切除术后肝细胞再生有促进作用 ,两药联合应用肝细胞再生更明显 ,其详细机制须待进一步研究。