广东人汉族群CTLA-4基因外显子1多态性与Graves病的相关性

目的探讨CTLA-4基因外显子1多态性与广东地区汉族人群Graves病的关系。方法以PCR-RFLP技术观察100名健康人与100例Graves病(GD)患者细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因外显子1的多态性。结果提示GD患者的CTLA-4外显子1的G49等位基因频率较正常对照组显著增高(P<0.01)。结论CTLA-4基因可能是广东地区汉族人群中GD的易感候选基因。     

自身免疫甲状腺病患者血清中IL-12和IL-18水平的分析

目的:提供自身免疫甲状腺病(AITD)患者体内Th1/Th2平衡紊乱的依据。方法:应用酶联免疫吸附法(ELISA)测定27例Graves病(GD)、24例甲状腺功能正常的桥本甲状腺炎(HT)、25例甲状腺功能低下的HT患者及20例正常对照者血清中IL12和IL18的浓度,并检测GD患者的甲状腺刺激性抗体。结果:GD患者与甲状腺功能正常的HT患者血中IL12、IL18水平无明显差异,但均高于正常对照者的相应水平。甲状腺功能低下的HT患者血中IL12和IL18的水平与正常对照者无差异。在GD和甲功正常的HT,IL18与IL12呈明显正相关。在GD,IL12和IL18均与其甲状腺刺激性抗体(TSAb)活性呈正相关。在甲状腺功能正常的HT还存在IL12和IL18二者与甲状腺球蛋白抗体(TgAb)的显著性正相关。结论:提示Th1型细胞在GD和HT两种AITD的发病中均起重要作用。通过抑制Th2型免疫反应,促进向Th1型的转变来治疗GD时,有可能导致病情恶化。     

肿瘤坏死因子-α基因多态性与安徽地区汉族人群Graves病易感性及患病早期TRAb水平的关联

目的 检测肿瘤坏死因子-a(tumour necrosis factor-α,TNF-α)基因启动子区的—863C/A、—857C/T、—238G/A等3个位点的单核苷酸多态性与格雷夫斯氏病(Graves disease,GD)与安徽地区汉族人群中发病的相关性,以探讨与GD有关的遗传背景.方法 应用聚合酶链式反应-序列特异性引物法(polymerase chain reaction and sequence specific primers,PCR-SSP)检测254例Graves病患者和212名正常对照TNF-α基因启动子区—863C/A、—857C/T、—238G/A三个位点的单核苷酸多态性,比较GD患者组与正常对照组、不同性别的GD患者之间的等位基因和基因型频率的分布情况.同时采用放射性免疫法测定早期GD患者的促甲状腺激素受体抗体(thyroid stimulating hormone receptor antibody,TRAb)水平,比较不同TRAb水平患者TNF-α基因这3个多态位点等位基因及基因型的频率分布情况.结果 (1)GD组—863 C/A位点A等位基因频率(16.73％)高于正常对照组(11.79％)(P＜0.05,OR=1.503);GD组AA+CA基因型频率(32.68％)明显高于正常对照组(23.58％) (P＜0.05,OR=1.573).—857 C/T、—238G/A位点等位基因及基因型频率在GD组与正常对照组间的差异均无统计学意义(P＞0.05).(2)将GD组按性别分组比较,结果显示3个位点的基因型及等位基因频率在男、女性间差异均无统计学意义(P＞0.05).(3)将早期GD患者按TRAb水平分组比较,结果显示3个位点的等位基因和基因型频率差异均无统计学意义(P＞0.05).结论 TNF-α基因—863C/A单核苷酸多态性可能与安徽地区汉族人群GD的发病具有相关性,而—857C/T、—238G/A位点的单核苷酸多态性与之无相关性;患者早期TRAb水平和GD患者的性别与TNF-α基因—863C/A、—857C/T、—238G/A三个位点的单核苷酸多态性无关联.     

广西地区壮族Graves病与CTLA4基因多态性相关性研究

目的分析CTLA4基因微卫星多态性与广西地区壮族Graves病（Graves’disease，GD）相关性。方法提取48例广西地区壮族GD患者和44名正常对照组的外周血白细胞基因组DNA，应用聚合酶链反应检测CTLA4第4外显子的3’非翻译区包含（AT）n[CTLA4（AT）n]重复序列的特异性等位基因。结果广西地区壮族人CTLA4微卫星多态性检出19种等位基因。壮族GD组106bp等位基因频率与正常对照组比较显著增高，差异有统计学意义（P〈0．05）。结论广西壮族GD患者与CTLA4基因多态性明显相关,CTA4（AT）n 106bp可能是广西壮族GD的易感等位基因。     

CD40基因5'非翻译区_1位点C/T多态性与Graves病药物治疗停药后复发的相关性

目的:探讨CD40基因5'非翻译区(5'untranslated region,5'UTR)_1位点C/T单核苷酸多态性与山东青岛地区汉族人群Graves病(Graves disease,GD)及药物治疗停药后复发的相关性。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术测定198例GD患者(其中GD初发组80例,GD早期复发组84例,GD晚期复发组34例)和110例正常对照者CD40基因5'UTR_1位点的基因型,并计算其基因型及等位基因频率。结果:①CD40基因5'UTR_1位点的基因型及等位基因频率在GD组和正常对照组中的分布有显著性差异(χ2=23.133,P=0.000;χ2=13.372,P=0.000),GD组CC基因型频率明显高于正常对照组(23.7%vs11.8%),TT基因型频率明显低于正常对照组(7.6%vs26.4%),GD组C等位基因频率明显高于正常对照组(58.1%vs42.7%);②CD40基因5'UTR_1位点的基因型频率在GD初发组与GD复发组的分布有显著性差异(χ2=7.926,P=0.019);GD复发组TT基因型频率明显低于GD初发组(3.4%vs1...     

4p14区段和CTLA-4基因多态性与Graves病相关

目的探讨中国安徽蚌埠地区汉族人群4p14区段位点rs6832151和CTLA-4基因4个SNPs(单核苷酸多态性)位点基因多态性与Graves病相关性,和基因-基因交互作用对Graves病的影响。方法提取611例诊断明确的GD患者和644名健康对照者的全基因组DNA,用Taq Man探针技术进行基因分型,使用Plink和Haploview等统计软件分析这些位点与蚌埠地区汉族人群Graves病的相关性。结果 4p14区段位点rs6832151的等位基因、基因型频率在GD组和对照组之间有差异(P0.05),CTLA-4基因区域内rs231804和rs231726两个SNP位点基因型在显性模型下差异显著(P0.05);GMDR模型显示CTLA-4基因内rs10197319、rs231726、rs231804、rs1024161位点和4p14区段内rs6832151位点组成的五阶模型(P=0.001)为最佳模型,CTLA-4基因内rs1024161和rs10197319位点之间上位效应分析结果有差异(P0.05)结论 4p14区段rs6832151,CTLA-4基因区域内rs231804和rs231726位点基因多态性与蚌埠地区汉族人群Graves病的遗传易感性相关;rs6832151(4p14区段)和rs10197319、rs231726、rs231804、rs1024161(CTLA-4基因)5个SNP位点间的基因-基因交互作用与Graves病相关,CTLA-4基因内rs1024161和rs10197319位点之间存在上位效应。     

内蒙地区汉族AITD与VitD受体基因多态性相关性分析

目的：探讨VitD受体（VDR）基因BsmI位点多态性与自身免疫性甲状腺疾病（AITD）的关系。方法：运用聚合酶链式反应-限制性片段长度多态性分析（PCR-RFLP）技术检测120例Graves’病（GD）患者,115例桥本氏甲状腺炎（HT）患者,80例甲状腺相关性眼病（TAO）患者及120例正常对照组的VDR-BsmI位点基因型,分析比较各组间等位基因及基因型分布频率差异。结果：①GD组的VDR-BsmI基因型及等位基因频率显著高于正常对照组,差异存在统计学意义（均P〈0.05）;HT组、TAO组与正常对照组间无显著差异（均P〉0.05）。②女性GD患者VDR-BsmI基因型及等位基因频率显著高于正常对照组,差异存在统计学意义（均P〈0.05）,男性GD组与正常对照组间均无显著性差异（P〉0.05）。③GD组不同基因型间的年龄、血清FT3、FT4、TT3、TT4、TSH、TGA、TPO-Ab水平均无显著差异（均P〉0.05）。结论：VDR-BsmI基因可能与GD尤其是女性GD患者发病相关而与HT发病无关,＂B＂等位基因是GD发病的易感因素。VDR-BsmI基因型的变化不影响GD患者的发病年龄、血清FT3、FT4、TT3、TT4、TSH、TGA、TPO-Ab的水平。     

家族性Graves病的遗传易感性与HLA-DQB1基因多态性研究

目的　检测中国天津Graves病 ,(GD)人群的HLA -DQB1的易感基因 ,并观察家族性GD与散发性GD之间的差异。方法　采用PCR -SSP方法 ,检测天津地区GD病人以及健康对照者HLA -DQB1基因型。结果　发现GD组与正常对照组相比HLA -DQB1 0 30 3基因频率有显著性差异 ,Pc <0 .0 1,RR =6 .76 9,有很强的相关性 ,家族性GD组与散发性GD组比较HLA -DQB1 0 30 1基因频率差异有显著性 ,P =0 .0 2 1,Pc =0 .4 2校正后无显著性差异。结论　认为天津地区汉族人具有DQB1 0 30 3基因时易患GD ,而具有GD家族史的人如具有DQB1 0 30 1基因也易患GD。     

FcRL3基因三个单核苷酸多态性与重庆汉族人群Graves病关联研究

目的 了解中国重庆地区汉族人群Fc受体样因子(Fc receptor-like proteins,FcRL3)基因启动子A/G,第2外显子C/G,第4外显子C/T多态性与Graves病(Graves disease,GD)的相关性.方法 采用聚合酶链反应限制性片段长度多态性分析方法结合直接测序技术,对重庆地区无亲缘关系的120名正常人和128例GD患者进行多态性研究,同时进行甲状腺功能和自身抗体的检测,应用Unphased1122和LDA1.0软件进行连锁不平衡和单倍型分析,用卡方检验分析基因型、等位基因和单倍型频率在GD组和对照组之间的差异.结果 GD组FcRL3基因3个多态性位点基因型和等位基因的频率与对照组相比,其差异均有统计学意义(P＜0.05).连锁不平衡分析显示启动子和第2外显子存在连锁不平衡,在构建的3个主要单倍型中,仅H2(G-G)单倍型频率GD组明显高于对照组(50.8%vs 35.8%,P＜0.05).除甲状腺疾病家族史与启动子多态性有关联(P%0.05),余临床特征与FcRL3多态性均无相关.结论 多个位点及单倍型分析提示FcRL3基因启动子A/G,第2外显子C/G,第4外显子C/T多态性可能是中国重庆地区汉族人群GD关联的危险因素.     

FcRL3基因启动子-169A/G多态性与Graves病的关联研究

目的 了解重庆地区汉族人群FcRL3基因启动子-169A/G的基因型分布;探讨该基因多态性与Graves病(GD)的相关性;探讨其基因型与甲状腺自身抗体、发病年龄、家族史和眼征的关系.方法 采用PCR-DNA直接测序技术对128例GD患者,120例正常人FcRL3基因启动子-169A/G位点进行多态性研究,同时进行甲状腺功能和自身抗体的检测.结果 GD组患者GG基因型和G等位基因频率明显高于对照组(分别为31.3% vs 21.7%,P<0.05;54.7% vs 43.3%,P<0.05).甲状腺疾病家族史在GG、AG、从三种基因型之间相比,其差异有统计学意义(P<0.05),甲状腺自身抗体、发病年龄和眼征在3种基因型之间相比,其差异均无统计学意义.结论 FcRL3基因启动子-169GG基因型和G等位基因可能为重庆地区汉族人GD患者的易感基因,该位点多态性可能与甲状腺疾病家族史有关,而与自身抗体的产生、发病年龄和眼征无明显相关性.     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.