重组耻垢分枝杆菌-Sj26GST疫苗有关毒性实验研究

目的初步研究重组耻垢分枝杆菌-Sj26GST疫苗对小鼠的有关毒性作用。方法 用重组耻垢分枝杆菌-Sj26GST疫苗免疫雄性BALB/c小鼠,16周后,称小鼠体重,摘眼球取血,测定小鼠的淋巴细胞、血红蛋白、白细胞及血小板含量;剩余血离心得到血清,测定小鼠肌酐及ALT;处死小鼠,分离出肺、肾、肝,并分别测定其重量。结果重组耻垢分枝杆菌-Sj26GST疫苗免疫的小鼠,其淋巴细胞数较对照组高(P<0.05),且在正常范围之内;小鼠体重、各脏器重量、各血象指标及血清肌酐和ALT含量与对照组比较差异无显著性(P>0.05)。结论重组耻垢分枝杆菌-Sj26GST疫苗免疫小鼠后对小鼠无系统毒性作用。     

表达结核杆菌ESAT-6基因重组耻垢分枝杆菌的免疫功能研究

目的研究表达结核杆菌ESAT-6基因重组耻垢分枝杆菌在动物体内的免疫功能。方法用表达结核杆菌ESAT-6基因重组耻垢分枝杆菌免疫BALB/c小鼠,通过淋巴细胞增殖实验检测重组耻垢分枝杆菌的免疫原性,利用流式细胞术分析小鼠T淋巴细胞亚群比例的变化,通过病理学切片观察重组耻垢分枝杆菌在动物体内的毒力。结果重组耻垢分枝杆菌诱导的脾淋巴细胞增殖反应、CD4＋T细胞比例均明显高于对照组;重组耻垢分枝杆菌不会导致脏器的器质性病变。结论表达结核杆菌ESAT-6基因重组耻垢分枝杆菌免疫原性显著增强,且毒力无明显改变,有望成为一种新型的结核病疫苗。     

表达结核杆菌ESAT-6基因重组耻垢分枝杆菌的免疫功能研究

目的研究表达结核杆菌ESAT-6基因重组耻垢分枝杆菌在动物体内的免疫功能。方法用表达结核杆菌ESAT-6基因重组耻垢分枝杆菌免疫BALB/c小鼠,通过淋巴细胞增殖实验检测重组耻垢分枝杆菌的免疫原性,利用流式细胞术分析小鼠T淋巴细胞亚群比例的变化,通过病理学切片观察重组耻垢分枝杆菌在动物体内的毒力。结果重组耻垢分枝杆菌诱导的脾淋巴细胞增殖反应、CD4+T细胞比例均明显高于对照组;重组耻垢分枝杆菌不会导致脏器的器质性病变。结论表达结核杆菌ESAT-6基因重组耻垢分枝杆菌免疫原性显著增强,且毒力无明显改变,有望成为一种新型的结核病疫苗。     

重组BCG-HSP70疫苗有关毒性实验研究

目的初步研究分枝杆菌重组疫苗rBCG -HSP70对小鼠的有关毒性作用。方法用分枝杆菌重组疫苗rBCG -HSP70免疫雄性BALB/c小鼠 ,16周后 ,称小鼠体重 ,摘眼球取血 ,测定小鼠的淋巴细胞、血红蛋白、白细胞及血小板含量 ;剩余血离心得到血清 ,测定小鼠肌酐及ALT ;处死小鼠 ,分离出肺、肾、肝并分别测定其重量。结果rBCG -HSP70疫苗免疫的小鼠 ,其淋巴细胞数较对照组高 (P<0.05) ;小鼠体重、各脏器重量、各血象指标、血清肌酐和ALT含量与对照组无差异 (P>0.05)。结论分枝杆菌重组疫苗rBCG -HSP70免疫小鼠后能提高小鼠淋巴细胞数 ,说明此疫苗能提高小鼠的免疫功能 ,对小鼠无系统毒性作用     

细粒棘球蚴重组蛋白GST诱导小鼠脾细胞增殖及对细胞因子水平的影响

目的探讨细粒棘球蚴重组蛋白GST(rEg.GST)诱导小鼠产生免疫保护力的机制。方法将rEg.GST与弗氏佐剂混合免疫小鼠,腹腔注射原头蚴制备包虫感染模型,分离脾淋巴细胞,用rEg.GST和刀豆蛋白A(ConA)诱导后,四甲基偶氮唑盐比色法(MTT)检测小鼠脾淋巴细胞的增殖情况;酶联免疫吸附法(ELISA)检测培养上清液中白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、γ-干扰素(IFN-γ)和白细胞介素-10(IL-10)的表达水平。结果重组蛋白免疫组在rEg.GST及Con A刺激状态下脾淋巴细胞增殖水平均高于佐剂组(P=0.003 0;P0.001)和PBS组(P=0.001 4;P=0.006 1)。与PBS组比较,rEg.GST组在免疫后、感染后的IL-2、IFN-γ、与IL-4的水平均增高(P=0.007 7;P=0.041 9;P=0.014 8);rEg.GST组免疫后与免疫前相比,IL-2、IFN-γ、IL-4与IL-10水平均增高(P=0.001 7;P=0.023 1;P=0.003 1;P=0.021 2);感染后与免疫后相比,IL-4与IL-10水平升高,IL-2水平则呈下降趋势(P=0.009 4;P=0.039 3;P=0.0179)。结论 rEg.GST能够促进脾淋巴细胞的增殖并同时活化辅助性T细胞1型(Th1)与2型(Th2)细胞。     

重组乙型肝炎疫苗和乙型肝炎表面抗原诱导细胞免疫应答

目的 探讨重组乙型肝炎(乙肝)疫苗和汉逊酵母菌表达的乙肝表面抗原(rHBsAg)诱导动物和人体细胞免疫应答的动态变化.方法 应用不同剂量rHBsAg免疫小鼠(BALB/c,H-2d),酶联免疫斑点法(ELISPOT)检测小鼠脾单个核细胞(MNC)体外刺激诱生IFN-γ的水平;单剂rHBsAg免疫后不同时间检测MNC、CD8+T淋巴细胞产生IFN-γ水平;同时测定免疫后不同时间细胞毒T淋巴细胞反应(CTL)活性;检测免疫单剂和多剂乙肝疫苗后小鼠MNC分泌IFN-γ、IL-2、IL-5和抗-HBs抗体水平;对乙肝感染标志阴性的4名成年人按0、1、2个月程序接种乙肝疫苗,检测免疫后外周血单个核细胞(PBMC)、CD8+T淋巴细胞分泌IFN-γ、IL-2和IL-4水平以及抗体动态.结果 应用ELISPOT法,汉逊rHBsAg免疫小鼠7 d时,可检测到IFN-γ应答,14 d时达到高峰;CTL在免疫后7 d时可检出,峰值位于28 d.在1～8μg免疫剂量范围内,MNCs IFN-γ免疫应答与剂量呈显著正相关(阳转率:Υ=0.951,P=0.049＜0.05;SFC:Υ=0.996,P=0.000＜0.05),在1～4 μg免疫剂量范围内,CD8+T淋巴细胞的IFN-γ与剂量也呈显著正相关(Υ=0.999,P=0.025＜0.05);三剂乙肝疫苗免疫小鼠诱生细胞免疫和体液免疫应答水平均显著高于单剂(P值均＜0.05);成年人接种汉逊乙肝疫苗后不同个体间细胞免疫和体液免疫应答的模式不同,IL-2、IL-4应答与个体抗体滴度有关.结论 用ELISPOT法成功测定了汉逊HBsAg免疫小鼠后不同淋巴细胞的细胞免疫剂量效应和CTL时间动态变化,并分析了成年人的细胞免疫应答特点,为规范疫苗细胞免疫评价提供了基础.     

结核亚单位疫苗强化BCG免疫策略对小鼠记忆T细胞维持的影响

目的 探索不同加强免疫策略对长期免疫记忆的影响,为结核疫苗的研究奠定理论基础.方法 将融合蛋白AMM、佐剂DDA和BCG-PSN混合构建AMM亚单位疫苗.选择50只C57BL/6小鼠(SPF级),按随机数字表法分为5组,每组10只,A组给小鼠注射磷酸盐缓冲液(PBS)作为对照;B组小鼠仅注射卡介苗(BCG)进行初免;C组小鼠BCG初免后,于第10周用AMM亚单位疫苗加强免疫;D组小鼠BCG初免后,分别于第8周、第10周用AMM亚单位疫苗加强免疫小鼠一次;E组小鼠BCG初免后,分别于第6周、第8周、第10周用AMM亚单位疫苗加强免疫小鼠一次.于第28周取出小鼠脾脏淋巴细胞,加入2.5μg/ml的Ag85B刺激72h后收集脾细胞培养上清,用ELISA测定Ag85B特异性脾淋巴细胞产生IFN-γ水平.结果 脾细胞受抗原Ag85B刺激后,BCG初免小鼠B组血清IFN-γ[(0.008±0.010)pg/ml]水平升高,但低于C组[血清IFN-γ(1.834±1.058)pg/ml]、D组[血清IFN-γ(2.337±0.964)pg/ml]、E组[血清IFN-γ(2.481±0.757) pg/ml],其差异均有统计学意义(P ＜0.05或P＜0.01),而A组血清IFN-γ[(0.005±0.048) pg/ml]水平均低于各免疫组(P ＜0.05或P＜0.01);C组血清IFN-γ水平均低于D、E两组,其差异有统计学意义(P＜0.05或P＜0.01);D组血清IFN-γ水平与E组比较差异无统计学意义(P＞0.05).结论 小鼠加强免疫强化的次数并非越多越好,适当的加强免疫次数可以诱导最持久的免疫记忆,亚单位疫苗加强免疫策略可能是影响免疫记忆的一个重要因素.     

Th1/Th2细胞相关因子对乙型肝炎疫苗免疫效果的影响研究

目的探讨Th1、Th2相关细胞因子IFN-γ,IL-4对乙型肝炎疫苗免疫效果的影响,为提高乙型肝炎疫苗免疫的成功率提供科学理论依据。方法选择年龄21~24岁接种过乙型肝炎疫苗的广西籍汉族大学生作为研究对象,根据接种乙型肝炎疫苗后产生不同免疫效果将研究对象分为抗-HBs中或强阳性组和抗-HBs阴性或弱阳性组;两组各88名,采用ELISA法分别检测两组研究对象血清中Th1/Th2细胞相关因子IFN-γ、IL-4的OD值,计算浓度值并进行比较分析。结果抗-HBs阴性或弱阳性组IFN-γ的平均表达水平为(3.88±4.57)pg/ml,显著低于抗-HBs中或强阳性组的平均表达水平(7.49±7.05)pg/ml,差异有统计学意义(P<0.01);抗-HBs阴性或弱阳性组IL-4的平均表达水平为(2.45±1.64)pg/ml,也显著低于抗-HBs中或强阳性组的平均表达水平(5.25±3.08)pg/ml,差异有统计学意义(P<0.01)。结论接种乙型肝炎疫苗后抗-HBs阴性或弱阳性者其体内Th1/Th2细胞相关因子IFN-γ和IL-4的表达水平均较产生抗-HBs中或强阳性者显著低下;提示Th1/Th2细胞相关因子IFN-γ、IL-4的表达水平可能影响机体乙型肝炎疫苗的免疫效果,似可应用IFN-γ、IL-4作为乙型肝炎疫苗佐剂以提高乙型肝炎疫苗的免疫效果。     

日本血吸虫31/32kDa重组抗原细胞免疫机制

目的探讨细咆免疫在重组日本血吸虫31／32kDa抗原（rSj31／32）保护性免疫机制中的作用。方法采用rSj31／32抗原免疫BALB／c小鼠，ELISA分别检测免疫前后小鼠血清干扰素（IFN-γ）和白细胞介素（IL-4）的含量，攻击感染后以脾细胞培养法检测经刀豆蛋白（ConA）和可溶性虫卵抗原（SEA）刺激后，小鼠睥细胞分泌IFN-γ和IL-4的水平。结果rSi31／32抗原免疫后血清IFN-γ的水平明显增加（P〈0．001），而IL-4的含量无明显变化；经SEA刺激，免疫组脾细胞产生较高水平的IFN-γ，而产生的IL-4水平较其他组低（P〈0．01）。结论细胞免疫在rSj31／32诱导的保护性免疫中起着重要作用。     

微小隐孢子虫pcDNA3.0-23重组质粒免疫效果评价

目的 比较微小隐孢子虫表面抗原CP23真核表达载体pcDNA3.0-23经不同免疫途径产生的免疫效果.方法 提取微小隐孢子虫基因组DNA,PCR扩增CP23基因片段,克隆至真核表达载体pcDNA.3.0,构建pcDNA3.0-23重组质粒,分别通过肌肉注射和滴鼻(粘膜)免疫2种途径免疫BALB/c小鼠,免疫3次,2周后检测抗CP23特异性抗体IgG滴度、小鼠脾脏、血清中CD4+和CD8+T细胞、细胞因子γ干扰素(IFN-γ);用微小隐孢子虫攻击感染被免疫小鼠,收集小鼠粪便,计算小鼠排出的卵囊量.结果 肌注组与滴鼻组小鼠血清抗CP23特异性抗体IgG滴度随免疫次数增加均明显升高,高于对照组及空质粒组(P＜0.05),肌注组高于滴鼻组(P＜0.05);肌注组与滴鼻组小鼠的CD4+T细胞、CD4+/CD8+比值均高于磷酸缓冲液(PBS)对照组及pcDNA3.0空质粒组(P＜0.05),但2种免疫途径的差异无统计学意义(P＞0.05);肌注组和滴鼻组脾细胞培养上清中IFN-γ明显高于对照组及空质粒组(P＜0.05);微小隐孢子虫攻击小鼠后,2种免疫途径的小鼠排出卵囊量明显少于对照组,且排出时间缩短,2种途径的差异无统计学意义.结论 pcDNA3.0-23重组质粒作为基因疫苗,可产生较好的细胞及体液免疫反应;不同的免疫途径可产生不同的免疫反应.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The human drama of genetics: 'hard' and 'soft' media representations of inherited breast cancer

This paper examines media coverage of 'breast cancer genetics', and explores its implications for public understanding. We present a content analysis of coverage in British newspapers and look at a variety of popular forms, including women's magazines, television soap opera and radio drama. Genetic/inherited risk receives a great deal of coverage across a wide range of media formats and outlets. Much of this attention has focused on individuals from 'high risk families' and dilemmas around prophylactic mastectomies. Through examining media coverage, combined with interviews with media personnel and their sources, we show why this story proved so attractive to the media and highlight the different production values which influence coverage. Finally, we introduce preliminary findings from focus group discussions to demonstrate how such 'human interest' framing has engaged audience attention and influenced public understandings. The paper concludes by highlighting the implications for analysing, predicting, and engaging with, media representations of science.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Worker education in the primary prevention of occupational dermatoses

This paper reports the evaluation of a skin care education programmeconducted on a fine chemicals manufacturing site where over1,000 employees are located. Approximately 60% are involvedin chemical manufacture. Over a 12 month period production staffreceived training in prevention of occupational dermatoses linkedto a site-wide poster initiative. The incidence of new casesof occupational dermatoses fell from 0.055 (70 cases in 1,277employees) to 0.021 (27 cases in 1,277 employees) before andafter the intervention respectively (p<0.0001). After otherfactors such as chemicals handled, observer bias and changesin reporting related to socioeconomic climate were taken intoaccount it is concluded that this study demonstrates the importanceof worker education as a tool for primary prevention of disease.Training materials such as video and poster presentations maybe effectively used in the chemical manufacturing industry asan adjunct to prevention and control of exposure to substanceshazardous to the skin. Such methods may also be used in otherindustries where there are significant risks of dermatoses.     

Regional Variation in Travel-related Illness acquired in Africa,March 1997–May 2011

To understand geographic variation in travel-related illness acquired in distinct African regions, we used the GeoSentinel Surveillance Network database to analyze records for 16,893 ill travelers returning from Africa over a 14-year period. Travelers to northern Africa most commonly reported gastrointestinal illnesses and dog bites. Febrile illnesses were more common in travelers returning from sub-Saharan countries. Eleven travelers died, 9 of malaria; these deaths occurred mainly among male business travelers to sub-Saharan Africa. The profile of illness varied substantially by region: malaria predominated in travelers returning from Central and Western Africa; schistosomiasis, strongyloidiasis, and dengue from Eastern and Western Africa; and loaisis from Central Africa. There were few reports of vaccine-preventable infections, HIV infection, and tuberculosis. Geographic profiling of illness acquired during travel to Africa guides targeted pretravel advice, expedites diagnosis in ill returning travelers, and may influence destination choices in tourism.     

Fatigue and health in a seafaring population

Background Occupational fatigue is relatively common withinthe general population and has been linked to reduced performance,injury and longer term ill-health. Despite growing acknowledgementof this problem in the maritime sector, little research hasbeen conducted into the risk factors, prevalence and consequencesof seafarers' fatigue. Aims To examine the prevalence of fatigue among seafarers, identifypotential risk factors and assess possible links with poor performanceand ill-health. Methods Cross-sectional questionnaire survey of seafarers workingin the offshore oil support, short-sea and deep-sea shippingindustries. A number of tools were used including the fatiguesubscale of the profile of fatigue-related symptoms, the CognitiveFailures Questionnaire, the General Health Questionnaire andthe SF36 General Health scale. Results In all, 1855 questionnaires were completed giving anoverall response rate of 20%. Fatigue symptoms were associatedwith a range of occupational and environmental factors, manyunique to seafaring. Reporting a greater number of risk factorswas associated with greater fatigue [e.g. OR = 2.53 (1.90–3.35)for those with three or four risk factors and OR = 9.54 (6.95–13.09)for those with five or more risk factors]. There was also astrong link between fatigue and poorer cognitive and healthoutcomes, with fatigue the most important of a number of riskfactors, accounting for 10–14% of the variance. Conclusions Seafarers' fatigue could impact on safety withinthe industry and may be linked to longer term individual ill-health.It can only be addressed by considering how multiple factorscombine to contribute to fatigue.     

The design of hazard risk assessment matrices for ranking occupational health risks and their application in mining and minerals processing

Two hazard risk assessment matrices for the ranking of occupational health risks are described. The qualitative matrix uses qualitative measures of probability and consequence to determine risk assessment codes for hazard-disease combinations. A walk-through survey of an underground metalliferous mine and concentrator is used to demonstrate how the qualitative matrix can be applied to determine priorities for the control of occupational health hazards. The semi-quantitative matrix uses attributable risk as a quantitative measure of probability and uses qualitative measures of consequence. A practical application of this matrix is the determination of occupational health priorities using existing epidemiological studies. Calculated attributable risks from epidemiological studies of hazard-disease combinations in mining and minerals processing are used as examples. These historic response data do not reflect the risks associated with current exposures. A method using current exposure data, known exposure-response relationships and the semi-quantitative matrix is proposed for more accurate and current risk rankings.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.