IL-18 水平表达及IL-18 基因多态性与哮喘病的相关性研究

目的:探讨IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C)多态性及血清IL-18水平与哮喘发生的关系。方法:选取我院301例哮喘患者作为哮喘组,并选取288例健康成人作为健康组。提取研究对象全血DNA,采用等位基因特异性引物PCR检测两组IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C),并对其PCR反应产物进行测序验证;观察IL-18基因多态性位点(IL-18/-607C/A,IL-18/-137G/C)等位基因频率分布,同时通过酶联免疫吸附法检测IL-18在不同组别血清浓度,分析影响哮喘发生的危险因素。结果:与对照组相比IL-18基因(-607C/A)、3种基因型、等位基因等差异较大(χ2=10. 24,P0. 001;χ2=50. 26,P0. 001),差异具有显著统计学意义。哮喘组基因位点-137G/C的CC与GG基因型差异有显著统计学意义(χ2=4. 717,P0. 05),其等位基因频率差异无显著性(χ2=3. 711,P0. 05);哮喘组患者血清IL-18水平显著低于健康组(t=85. 34,P0. 001),其中基因多态性位点(-607C/A) CC基因型的哮喘患者血清IL-18的水平为(18. 02±3. 92) pg/ml,携带AA基因型患者IL-18的水平为(41. 68±8. 08) pg/ml,两者比较差异具有统计学意义(t=22. 26,P0. 001);基因多态性位点(-137G/C) 3种基因型哮喘患者血清IL-18的水平差异无统计学意义(F=0. 281,P0. 05)。结论:哮喘患者血清IL-18水平降低,提示哮喘的发生可能与血清IL-18水平低下有关。IL-18多态性位点(IL-18/-607C/A,IL-18/-137G/C)的基因分型中携带(-607C/A) AA基因型的人群患哮喘风险更大。     

白细胞介素-18基因多态性与广西壮族系统性红斑狼疮的遗传易感性

目的 探讨白细胞介素-18(interleukin 18,IL-18)基因单核苷酸多态性与广西壮族系统性红斑狼疮(systematic lupus erythematosus,SLE)易感性之间的关系.方法 以115例SLE患者和160名健康对照者为研究对象,应用聚合酶链反应-限制性片段长度多态性和DNA测序的方法对IL-18基因-137G/C、-607C/A单核苷酸多态性进行基因分型.结果 IL-18基因-137G/C多态性在SLE组和正常人群中的分布差异无统计学意义(P>0.05),而IL-18基因-607C/A多态性在两组人群中的分布差异有统计学意义(P<0.05),等位基因频率的相对风险分析发现,-607 C等位基因携带者患系统性红斑狼疮的风险是-607A等位基因的1.619倍(OR=1.619,95%CI:1.150-2.281).联合基因型分析发现,IL-18的-137G/-607C等位基因频率在SLE组中显著高于对照组(P<0.05).-137G/-607C等位基因携带者显著增加了SLE的发病风险(OR=1.484,95%CI:1.056-2.087).结论 IL-18基因-607C/A多态性与SLE的发病具有相关性,其中-607 C等位基因可能是SLE的遗传易感基因.     

汉族人白细胞介素-18基因启动子多态性与慢性乙型肝炎的相关性研究

目的 探讨中国汉族人白细胞介素-18（interleukin-18,IL-18）基因启动子单核苷酸多态性及其与慢性乙型肝炎易感性之间的关系。方法 应用序列特异性引物一聚合酶链反应技术，检测231例慢性乙型肝炎患者和300名正常人儿．馏基因启动子-607C/A、-137G／C单核苷酸多态性位点基因型。结果 正常对照组和慢性乙型肝炎组中，IL-18基因启动子-607C/A位点3种基因型频率分别为CC型：0．22（66／300）和0．27（62／231），CA型：0．53（160／300）和0．50（116／231），AA型：0．25（74／300）和0．23（53／231）；IL-18基因启动子-137G／C位点3种基因型频率分别为GG型：0．67（202／300）和0．79（182／231），GC型：0．30（90／300）和0．19（45／231），CC型：0．03（8／300）和0．02（4／231）。经Y0检验，慢性乙型肝炎组IL-18基因启动子-137GG分布频率显著高于正常对照组（X^2=8．55，P=0．003），而-607C／-137C和-607A／-137C单倍型频率显著低于正常对照组。进一步比较慢性乙型肝炎患者儿．馏基因启动子多态性与乙型肝炎病毒（hepatitis Bvirus，HBV）DNA复制的关系，发现高水平HBV—DNA组-607位点AA基因型分布频率明显低于低水平HBV—DNA组（Y2=6．03，P=0．014）。结论 汉族人慢性乙型肝炎与IL-18基因启动子-607C/A、-137G／C单核苷酸多态性相关，其中IL-18基因启动子-137位点C等位基因可能对机体HBV感染有保护作用，而启动子-607位点AA型对感染后HBV—DNA的复制可能有抑制作用。     

白细胞介素-18基因多态性与其表达量关系的研究

目的:探讨IL-18基因启动子-607C/A、-137G/C位点多态性是否影响其表达量。方法:选择80例体检健康个体,确定IL-18基因启动子区-137G/C、-607C/A位点基因型,分离上述研究对象外周血单个核细胞(PeripheralBloodMonocytes,PBMC),统一浓度培养24h后,收集培养细胞和上清液。采用ELISA检测上清液中IL-18的含量,并用RT-PCR检测培养细胞中IL-18mRNA的水平。结果:IL-18基因启动子-607位点CC、CA和AA基因型个体PBMC分泌IL-18的浓度分别为(11.54±6.48)ng/ml、(10.92±5.16)ng/ml和(11.79±3.18)ng/ml,表达IL-18mRNA水平分别为0.878±0.633、0.877±0.521和0.881±0.400;IL-18基因启动子-137位点GG、GC或CC基因型个体PBMC分泌IL-18的浓度分别为(11.27±5.42)ng/ml和(11.31±4.62)ng/ml,表达IL-18mRNA水平分别为0.835±0.485和0.984±0.613。两个位点各基因型间个体PBMC分泌和表达IL-18水平比较,差异无显著性(P>0.05)。结论:IL-18基因外显子1上游启动子-607C/A、-137G/C位点基因多态性对IL-18分泌和表达量没有明显影响。     

Interleukin-18基因启动子区单核苷酸多态性与肝细胞癌遗传易感性关系的研究

目的探讨白细胞介素18(IL-18)基因启动子区-607C/A(rs1946518)和-137G/C(rs187238)单核苷酸多态性(SNP)与肝细胞癌(肝癌)遗传易感性的关系。方法应用序列特异性引物-聚合酶链反应(PCR-SSP)技术,检测228例肝癌患者和300例健康对照者IL-18基因启动子-607C/A(rs1946518)、-137G/C(rs187238)单核苷酸多态性位点基因型,分析肝癌患者和对照组基因型频率和等位基因频率分布。结果肝癌组SNP位点rs187238 G等位基因的频率明显高于对照组(OR=1.1891,95%CI=1.0106-1.5633,P=0.026)。携带rs187238 GG基因型的肝癌患者较多(OR=1.5168,95%CI=1.1490-1.8322,P=0.010)。分层分析发现,rs1946518位点上AA基因型与肝癌发病的关联在饮酒的肝癌患者中更加显著(P=0.024),而且rs187238位点上GC/CC基因型与肝癌发病的关联在出现肝癌复发的患者中更加显著(P=0.005)。结论 IL-18基因启动子区-137G/C(rs187238)GG基因型与肝癌遗传易感性有关联。而rs1946518位点AA基因型和rs187238位点GC/CC基因型分别与肝癌患者饮酒和肝癌复发有关联。     

IL-6基因多态性与变应性鼻炎的关联性

目的探讨白细胞介素6(IL-6)基因启动子区-634C/G和-572C/G位点多态性与变应性鼻炎的关联性。方法应用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)检测105例PHC患者和130例健康对照者IL-6基因启动子区-634和-572位点多态性。结果 IL-6基因-634C/G多态性在变应性鼻炎组和对照组的分布差异不显著性(P0.05),而IL-6基因-572C/G多态性在两组人群中的分布差异显著(P0.05)。等位基因频率的相对风险分析发现,G等位基因携带者患冠心病的风险是C等位基因的1.849倍[相对比值比(OR)=1.849,95%可信区间(CI):1.187～2.879]。结论 IL-6-572基因多态性与变应性鼻炎的发病有相关性,G等位基因可能是变应性鼻炎的遗传易感基因。     

IL-10通路基因多态性与哮喘及OPN、TGF-β1水平相关性探讨

目的探讨IL-10通路基因多态性与哮喘以及OPN、TGF-β1水平的关系。方法选择我院63例哮喘患儿为研究组,50例健康儿童为对照组,均采集外周血标本,采用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测IL-10通路基因多态性,酶联免疫吸附试验(ELISA)检测外周血白介素-10(IL-10)、骨桥蛋白(OPN)及转化生长因子β1(TGF-β1)水平,分析IL-10通路基因多态性与哮喘、IL-10、OPN、TGF-β1的相关性。结果哮喘组患儿IL-10通路基因分型以AG+AA型比例最高(76.19%),A等位基因频率39.68%,G等位基因频率60.32%,对照组GG型36.00%,AG+AA型64.00%,A等位基因频率51.00%,G等位基因频率49.00%,2组等位基因频率之间差异具有统计学意义(P<0.05)。研究组患儿血清IL-10、OPN、TGF-β1水平均高于对照组[(95.37±26.88)pg/ml vs(81.05±17.73)pg/ml、(19.52±5.37)ng/ml vs(14.19±3.95)ng/ml、(70.35±12.54)pg/...     

IL-10基因启动子多态性与皖南地区汉族人群支气管哮喘的相关性研究

目的:探讨IL-10基因启动子-1082G/A(rs1800896)、-819C/T(rs1800871)、-592C/A(rs1800872)位点多态性与安徽皖南地区汉族人群支气管哮喘的相关性。方法:采用病例-对照方法,用聚合酶链反应及直接基因测序法比较183例支气管哮喘组与151例正常人对照组之间基因型、等位基因频率的差异。结果:哮喘组IL-10基因启动子-1082G/A、-592C/A位点基因型与对照组相比有差异(P<0.05),其等位基因型频率在哮喘组和对照组间亦有差异(P<0.05)。而-819C/T位点基因型及等位基因型频率在哮喘组和对照组间均无差异(P>0.05)。结论:IL-10基因启动子rs1800896(-1082G/A)位点和rs1800872(-592C/A)位点的多态性可能与安徽皖南地区汉族哮喘相关;而rs1800871(-819C/T)位点的多态性可能与安徽皖南地区汉族哮喘无相关。     

白介素-10-627基因多态性和儿童哮喘的相关性研究

目的探讨白介素-10(IL-10)基因-627位点多态性与昆明地区儿童哮喘的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法,检测50例哮喘儿童和36例健康儿童IL-10基因-627位点基因型,比较两组IL-10基因-627位点的基因型和等位基因分布频率。结果哮喘组和健康组3种基因型CC、CA、AA分别为:12.0%、48.0%、40.0%;8.3%、50.0%、41.7%。两组基因型分布差异无显著性(P>0.05)。哮喘组和健康组C和A的等位基因分布频率分别为:36.0%、64.0%;31.9%、68.1%。两组等位基因分布频率差异无显著性(P>0.05)。结论本研究表明IL-10基因-627位点多态性可能与昆明地区儿童哮喘易感性无关。     

湖北汉族人群白细胞介素18基因启动子区多态性研究

目的 :研究白细胞介素 18(IL 18)基因启动子区 - 137G/C、- 6 0 7C/A位点多态性在湖北汉族健康人群中的分布。方法 :随机选择 187例湖北地区无血缘关系的汉族健康人 ,用序列特异性引物聚合酶链反应技术检测IL 18基因启动子区 - 137G/C、- 6 0 7C/A位点单核苷酸多态性 (SNP) ,并进行不同种族间比较。结果 :湖北地区汉族健康人群IL 18基因启动子区 - 137位点基因型以GG型 ( 6 7% )多见 ,其次为GC型 ( 30 % )和CC型 ( 3% ) ;其等位基因以G型 ( 82 % )最为常见。而 - 6 0 7位点基因型以CA型 ( 6 0 % )多见 ,其次为CC型 ( 2 1% )和AA型 ( 19% ) ;其等位基因以C型 ( 51% )多见。与瑞典、波兰、澳大利亚等人群相比 ,该位点多态性分布差异存在显著性 (P <0 .0 5) ,而 - 137G/C位点基因型分布与亚洲日本人群相接近 (P >0 .0 5)。结论 :湖北地区汉族人群IL 18基因启动子区 - 137G/C、- 6 0 7C/A位点存在多态性 ,其在不同种族间的分布可能存在显著性差异。     

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.