钩端螺旋体外膜疫苗的反应性和免疫效果研究

对国内首次研制的钩端螺旋体外膜疫苗接种人体的反应性,血清学效果和流行病学效果进行研究。先后对两价（含黄疸出血群赖型,七日热群七日热型）,三价（含黄疸出血群赖型,七日热群七日热型,流感伤寒群流感伤寒型,五价（含黄疸出血群赖型,七日热群七日热型,流感伤寒群流感伤寒型,秋季热群秋季热型,犬群犬型）外膜疫苗,菌体疫苗和安慰剂,分组进行全身和局部反应观察;并以显微镜凝集试验测定各型抗体;对两价外膜疫苗进行流行病学保护效果考核。结果两价和多价钩体外膜疫苗反应轻微,安全性良好;血清学效果显示,抗体阳转率和滴度均高于同期相应菌体疫苗诱导的同型抗体水平2倍以上,提示外膜疫苗有较好的免疫原性,流行病学效果在湖北省荆州和石首两市考核,按血清学阳性病例统计,其保护率可达95．57％以上。说明上述疫苗性质稳定,反应轻微,安全性良好,血清学效果理想,两价疫苗有较好的保护效果,可以逐步推广应用。     

人感染钩体菌群与免疫血清群及交叉凝集关系研究

为了解人间自然感染各群钩端螺旋体（钩体）后产生的免疫抗体血清群、交叉凝集（交凝）、效价及相互关系,作者对病原学阳性并做过双份血清ＭＡＴ的６４份资料作了综合分析,结果表明：６４株钩体属于１２个群,其中１３株菌的感染者血清呈阴性反应,占２０．３１％;５１例呈阳性,占７９．６９％,有１４个血清群,效价１∶１００～１∶６４００;１２个菌群感染者的血清交凝反应较为普遍,效价１∶１００～１∶３２００;效价高低及交凝群数,因感染菌群而异。较为特殊的是１１个菌群感染者的血清中均不见与流感伤寒群钩体的交凝现象。本文对人间分离钩体菌群与免疫血清群构成比例互不吻合的问题作了解释,为钩体病的免疫及血清流行病学补充了新论据     

水痘疫苗在学校暴发疫情中保护效果的回顾性队列研究

目的了解水痘疫苗在学校等集体单位水痘暴发疫情中的保护效果。方法选择佛山市2012年水痘暴发疫情的学校,按年龄分层,以接种水痘疫苗作为暴露因素,采用回顾性队列研究方法,评价水痘疫苗的保护效果。结果共有143名学生纳入研究对象,水痘疫苗的保护率为69.18%。按年龄分层分析发现,6～7岁组水痘疫苗保护率为86.12%,而9～11岁组水痘疫苗未显示保护作用。结论水痘疫苗对学校等集体单位水痘暴发疫情的控制具有良好的效果。但由于疫苗免疫机体后所产生的抗体衰减,小学高年级学生应适时加强接种一剂次水痘疫苗。     

高效价冻干人用狂犬病疫苗暴露后免疫程序的研究

初步确定高效价冻干人用狂犬病疫苗（6．0IU／剂）暴露后免疫程序。制备高效价的冻干人用狂犬病疫苗（6．0IU／剂）,以狂犬病街毒CNX8601和BD06分别攻击小鼠和比格犬的咬肌,接种不同效价的狂犬病疫苗,以RFFIT法检测中和抗体,根据动物死亡情况,计算暴露后疫苗保护率,对不同效价的疫苗进行中和抗体测定和保护率统计分析。在以小鼠为实验动物的疫苗保护率研究中,冻干人用狂犬病疫苗（3．1IU／剂）0／3／7／14／28免疫程序的保护率为40．6％,高效价的冻干人用狂犬病疫苗（6．0IU／剂）0／3／14免疫程序的保护率为56．2％,中和抗体比较,P〈0．05,2组间有显著性差异;在以比格犬为实验动物的保护效果研究中,冻干人用狂犬病疫苗的保护率（3．1IU／剂）为70％;高效价的冻干人用狂犬病疫苗（6．0IU／剂）的保护率为80％,中和抗体的比较,P〉0．05,没有显著性差异。高效价冻干人用狂犬病疫苗暴露后免疫程序可初步确定为0、3、14d免疫。     

钩端螺旋体膨胀试验用于快速鉴定菌群的研究

本文报导的膨胀试验,为一种鉴定钩端螺旋体菌群的快速而可靠的方法,经近二年的实验研究和现场考核应用,其结果可归述如下： 1．据我们实验研究,膨胀试验的抗血清浓度以1：500倍稀释为宜(指血清凝溶效价为1：12800之通常定群用诊断血清)。当此稀血清与同群钩端螺旋体各一接种环在玻片上加以混和,并覆以盖玻片,置于400倍暗视野下,于10分钟内观察结果,阳性时,可见钩端螺旋体发生膨张、伸长和部分溶解等显著形态学变化。 2．对304株不同群别的钩端螺旋体地方株(病人37,猪16,鼠251)和国内13群14型标准菌分别进行了膨胀试验定群鉴定,并同时以凝溶试验作对照,结果两者完全相符。 3．膨胀试验具有快速、简单、特异性高等优点。本文结果表明该法较凝溶试验更为优越,特别是可在“非常”条件下用于快速鉴定钩端螺旋体菌群。     

问号钩端螺旋体属特异性OmpL1s抗原膜定位及其自然抗体应答

为了确定问号钩端螺旋体(简称钩体)属特异性OmpL1s抗原膜定位及其自然抗体应答情况和抗体类型,为OmpL1s用于研制通用性钩体基因工程疫苗及检测试剂盒抗原提供依据。采用显微镜凝集试验(MAT)检测四川地区156份钩体病人血清标本。用PCR和核苷酸序列分析,了解中国流行的钩体主要血清群ompL1基因型。采用常规基因工程技术构建ompL1/1和ompL1/2主要基因型原核表达系统,Ni-NTA亲和层析法提纯目的重组表达产物rOmpL1/1和rOmpL1/2。采用胶体金免疫电镜技术,对OmpL1s进行膜定位。建立了基于rOmpL1s的ELISAs,检测钩体病人血清中特异性抗体水平及其类型。试验结果表明,黄疸出血群钩体仍然是四川地区最主要的优势钩体血清群。中国流行的钩体主要血清群ompL1基因可有ompL1/1和ompL1/2两个基因型,两者核苷酸和氨基酸序列相似性之间有较明显的差异。OmpL1s是位于钩体外膜表面的蛋白分子。不同稀释度的156例钩体病人血清标本中,rOmpL1/1和rOmpL1/2特异性IgM阳性率分别为67.9%～79.5%和75.0%～75.6%,特异性IgG阳性率分别为71.8%～79.5%和75.0%～76.9%。上述试验结果提示,OmpL1s是位于钩体表面属特异性蛋白抗原。自然感染钩体时,rOmpL1/1和rOmpL1/2均可诱导机体体液免疫应答并产生IgM和IgG两类血清抗体,且两者之间有广泛的抗原交叉反应。rOmpL1/1和rOmpL1/2可作为研制通用性钩体基因工程疫苗和检测试剂盒的候选抗原。     

间接FLISA法检测钩端螺旋体特异性IgM方法的探讨

为研制钩端螺旋体（钩体）特异性IgM检测试剂,并用于早期诊断钩体病,以钩体外膜蛋白为抗原,探索间接ELISA法检测钩体特异性IgM的各项实验条件,并对钩体病患者血清标本进行检测,结果,１０５份健康人血ＩgM阴性,钩体IgM阳性血清可被特异性阻断,２－巯基乙醇破坏试验阳性,试剂存放４℃和３７℃4天的检测结果基本一致,检测临床钩体病人112份血清,IgM阳性83份,阳性率74．11％,与常规TAT法基本一致,0－7病日的阳性率明显高于MAT法,说明该法检测钩体病IgM具有特异,敏感,快速,稳定,简便等优点,对钩体病早期诊断有一定的价值。     

人用精制Vero细胞狂犬病疫苗的保护性试验

用ＣＴＮ－１Ｖ株生产的精制Ｖｅｒｏ细胞狂犬病疫苗腹腔免疫小鼠后,再用狂犬病毒街毒株ＳＢＤ０７脑内和肌肉攻击,结果表明稀释５倍疫苗的保护率分别为８８．９％和９０％,且５倍稀释疫苗的保护效果与原苗相当,此研究证明ＣＴＮ－１Ｖ株能用来作为疫苗的生产毒株。     

问号钩端螺旋体中一个新的OmpA家族蛋白抗原性及保守性研究

目的克隆表达和鉴定问号钩端螺旋体(L.interrogans)黄疸出血群赖型赖株中一个新的外膜蛋白(Omp)A家族基因LA0301,研究LA0301编码蛋白的抗原性和在15个钩端螺旋体(简称钩体)血清群代表株中的保守性,探讨其在疫苗研究中的意义。方法生物信息学软件分析预测LA0301的特征。构建原核表达重组体pQE31-LA0301,经IPTG诱导后用十二烷基磺酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)及蛋白质印迹法(Western blot)鉴定表达情况。用表达的重组蛋白免疫BALB/c小鼠,Western印迹检测其免疫反应性和在不同血清型钩体中的保守性。酶联免疫吸附试验(ELISA)和Western印迹检测兔抗钩体全菌血清中的LA0301编码蛋白的抗体。结果生物信息学预测结果显示,LA0301具有OmpA家族的结构域。克隆表达了重组质粒pQE31-LA0301,重组蛋白能刺激BALB/c小鼠产生特异性抗体,效价为1:32000。在兔抗钩体全菌血清中检测到特异的LA0301蛋白抗体,并在15个血清群的代表株钩体中均可检测到LA0301蛋白。结论LA0301蛋白是问号钩体中一个新的OmpA家族蛋白,具有良好的抗原性和保守性,并且能在钩体感染的过程中刺激机体产生相应的抗体。为进一步研究钩体新型疫苗候选基因奠定了基础。     

钩端螺旋体外膜菌苗的研究I．菌苗的制备、性质及免疫原性

本文报道有关钩端螺旋体外膜菌苗的研究结果。通过不同孔径微孔滤膜收集盐变细胞(0．85～1．2微米)及纯化外膜(0.45微米),方法简便、省时,且不需贵重仪器,为大量制备钩端螺旋体(以下简称钩体)外膜菌苗提供了新的途径。黄疸出血群及波摩那群钩体外膜,在电子显微镜下的形态大多里圆形成不规则形。其化学组成黄疽出血群外膜中含蛋白质3 7．77％,碳水化合物22．21％及类脂质1 7．77％;后者则含蛋白质59．7 2％,碳水化合物13．69％,类脂质¨．90％。除强碱相似文献   

Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM

The association of the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene with type 2 diabetes was examined using a Japanese population (n (M/W): 4585 (2085/2500); age: 62.6 ± 10.9 years). HbA1c levels and frequency of diabetic subjects were significantly higher in subjects with genotypes with Cys allele than in those without (p = 0.032 and 0.037, respectively). Multiple logistic regression analysis showed that genotypes with Cys allele were significantly associated with diabetes (OR: 1.32, p = 0.0289). In subjects whose glucose tolerance was classified by FPG and 2-h PG (n = 1.634), the association was more substantial (genotypes with Cys allele vs. without, OR: 1.70, p = 0.0059; genotypes Cys/Cys vs. Ser/Ser, OR: 2.19, p = 0.0008). In subjects with genotype Ser/Ser, the insulin secretion index, HOMA-β, increased in the subjects with glucose intolerance and decreased in the subjects with diabetes, while, in subjects with genotypes Ser/Cys + Cys/Cys, HOMA-β decreased as the glucose tolerance progressed (p for trend = 0.010).     

从系统动物学的诞生和发展探讨现代动物学研究的特点

新技术新理论的不断发展推动着系统动物学的诞生,其迅速发展也说明了动物学领域宏观研究和微观研究在更高程度上相互渗透的特点。     

Unbiased and Locally Efficient Estimation of Genetic Effect on Quantitative Trait in the Presence of Population Admixture

Summary Population admixture can be a confounding factor in genetic association studies. Family‐based methods ( Rabinowitz and Larid, 2000 , Human Heredity 50, 211–223) have been proposed in both testing and estimation settings to adjust for this confounding, especially in case‐only association studies. The family‐based methods rely on conditioning on the observed parental genotypes or on the minimal sufficient statistic for the genetic model under the null hypothesis. In some cases, these methods do not capture all the available information due to the conditioning strategy being too stringent. General efficient methods to adjust for population admixture that use all the available information have been proposed ( Rabinowitz, 2002 , Journal of the American Statistical Association 92, 742–758). However these approaches may not be easy to implement in some situations. A previously developed easy‐to‐compute approach adjusts for admixture by adding supplemental covariates to linear models ( Yang et al., 2000 , Human Heredity 50, 227–233). Here is shown that this augmenting linear model with appropriate covariates strategy can be combined with the general efficient methods in Rabinowitz (2002) to provide computationally tractable and locally efficient adjustment. After deriving the optimal covariates, the adjusted analysis can be carried out using standard statistical software packages such as SAS or R . The proposed methods enjoy a local efficiency in a neighborhood of the true model. The simulation studies show that nontrivial efficiency gains can be obtained by using information not accessible to the methods that rely on conditioning on the minimal sufficient statistics. The approaches are illustrated through an analysis of the influence of apolipoprotein E (APOE) genotype on plasma low‐density lipoprotein (LDL) concentration in children.     

发展性阅读障碍的产生机制——从行为到遗传研究

发展性阅读障碍(developmental dyslexia,DD)是一种特殊的学习障碍,探索DD的产生机制有助于寻求DD儿童的鉴别和治疗方法.目前拼音文宁国家对DD的产生机制研究很多,结果也很丰富,但是很多观点还不一致.汉语DD研究起步较晚,各方面还不够深入和完善.简述了DD在认知、脑神经和基因方面的研究进展,对拼音文字DD与汉语DD的研究结果进行了对比,以揭示不同语言文字系统下DD者的认知神经差异.研究认为,应该大力加强对汉语DD的探究,这样不但为中国DD儿童的诊治提供理论基础,也可以为DD的语种特异性问题提供科学依据.     

Estimation of the Power of the Kruskal-Wallis Test

Power calculations of a statistical test require that the underlying population distribution(s) be completely specified. Statisticians, in practice, may not have complete knowledge of the entire nature of the underlying distribution(s) and are at a loss for calculating the exact power of the test. In such cases, an estimate of the power would provide a suitable substitute. In this paper, we are interested in estimating the power of the Kruskal-Wallis one-way analysis of variance by ranks test for a location shift. We investigated an extension of a data-based power estimation method presented by Collings and Hamilton (1988), which requires no prior knowledge of the underlying population distributions other than necessary to perform the Kruskal-Wallis test for a location shift. This method utilizes bootstrapping techniques to produce a power estimate based on the empirical cumulative distribution functions of the sample data. We performed a simulation study of the extended power estimator under the conditions of k = 3 and k = 5 samples of equal sizes m = 10 and m = 20, with four underlying continuous distributions that possessed various location configurations. Our simulation study demonstates that the Extended Average × & Y power estimation method is a reliable estimator of the power of the Kruskal-Wallis test for k = 3 samples, and a more conservative to a mild overestimator of the true power for k = 5 samples.     

Analysis of dyslexia candidate genes in the Raine cohort representing the general Australian population

Several genes have been suggested as dyslexia candidates. Some of these candidate genes have been recently shown to be associated with literacy measures in sample cohorts derived from the general population. Here, we have conducted an association study in a novel sample derived from the Australian population (the Raine cohort) to further investigate the role of dyslexia candidate genes. We analysed markers, previously reported to be associated with dyslexia, located within the MRPL19/C2ORF3, KIAA0319, DCDC2 and DYX1C1 genes in a sample of 520 individuals and tested them for association with reading and spelling measures. Association signals were detected for several single nucleotide polymorphisms (SNPs) within DYX1C1 with both the reading and spelling tests. The high linkage disequilibrium (LD) we observed across the DYX1C1 gene suggests that the association signal might not be refined by further genetic mapping.     

Nonparametric identification of the minimum effective dose

We consider identifying the minimum effective dose (MED) in a dose-response study, where the MED is defined to be the lowest dose level producing an effect over that of the zero-dose control. Proposed herein is a nonparametric procedure based on the Mann-Whitney statistic incorporated with the step-down closed testing scheme. A numerical example demonstrates the feasibility of the proposed nonparametric procedure. Finally, the comparative results of a Monte Carlo level and power study for small sample sizes are presented and discussed.     

Distribution of HLA antigens in Kotas and Badagas of the Nilgiri Hills, South India

Blood samples from 103 Kotas and 58 Badagas residing in the Nilgiri Hills, South India, were examined for HLA-A and -B antigen profiles. The Kota group was characterized by fairly high frequencies of A2 and B7 antigens as well as the haplotype A2-B7. The frequencies of Aw19, A28, and Bw22 were found to be higher in Badagas than in Kotas. The results are compared with the literature available on other Indian populations.     

根系分泌物研究方法(综述)

根系分泌物是植物与土壤进行物质、能量与信息交流的重要载体物质.研究根系分泌物的种类、数量对了解植物与土壤及根际微生物相互作用机理具有重要指导意义,根系分泌物研究方法的选择对研究结果有重要的影响.本文着重讨论根系分泌物收集、分离纯化及鉴定的常用方法,并列举特定根系分泌物的研究方法,旨在为根系分泌物的研究提供借鉴和参考.