镉相关翻译启动因子TIF3致Ras癌基因蛋白的异常表达

目的 研究镉相关翻译启动因子TIF3对多种细胞肿瘤相关基因表达的影响,探索镉的分子致癌机制。方法应用TIF3基因真核细胞稳定表达系统和Western blot检测技术,用各种单克隆抗体检测细胞肿瘤相关基因蛋白的表达情况。结果 相对于载体转染中国仓鼠卵巢(CHO)对照细胞,在4株具有高效稳定表达TIF3编码蛋白质的CHO细胞系中均有pan—ras癌基因蛋白异常表达,其编码蛋白(21kDa)含量均明显高于对照组;其余肿瘤相关基因蛋白如c—myc．c-jun,MDM2,ODC,P16,p53,Cyclin D1的表达蛋白在TIF3转基因细胞与对照细胞之间未见明显差别。结论 镉相关翻译启动因子TIF3是一种镉应答原癌基因,TIF3的超额表达可导致Ras癌基因蛋白异常表达,这可能是镉应答原癌基因TIF3的分子致癌机制。     

金属镉应答新基因TEF-1δ的致癌力鉴定

目的 前期研究已发现金属镉应答新基因TEF-1δ转染NIH3T3细胞可致其编码蛋白质表达升高而引起细胞转化.本研究的目的是对TEF-1δ基因转化NIH3T3细胞的致癌能力和致瘤性进行鉴定.方法软琼脂集落形成试验和裸鼠成瘤实验.结果所有4株不同的TEF-1δ转染发生转化的NIH3T3细胞在软琼脂培养中均显示锚非依赖性生长能力,形成明显的细胞集落.而非转化对照细胞在软琼脂上则无生长能力.转化细胞和对照细胞分别给裸鼠皮下注射(每组4只,5组共20只),1周后,转化细胞组的绝大部分裸鼠下背部皮下开始出现肿瘤,4周后所有4种不同转化细胞株接种的裸鼠全部长出大小不等的肿瘤,但非转化对照细胞于第5周后仍无一只裸鼠出现肿瘤.提示TEF-1δ转基因转化细胞属恶性转化细胞,具有明显的致癌能力和致瘤作用.结论根据本研究结果及前期发现,可以认为新发现的TEF-1δ是一个镉应答原癌基因.     

金属镉应答新基因TEF-1β的致癌力鉴定

目的 前期研究已发现金属镉应答新基因TEF-1β转染NIH3T3细胞可致其编码蛋白质表达升高而引起细胞转化。本研究的目的是对TEF-1β基因转化NIH3T3细胞的致癌能力和致瘤性进行鉴定。方法软琼脂集落形成试验和裸鼠成瘤实验。结果所有4株不同的TEF-1β转染发生转化的NIH3T3细胞在软琼脂培养中均显示锚非依赖性生长能力，形成明显的细胞集落。而非转化对照细胞在软琼脂上则无生长能力。转化细胞和对照细胞分别给裸鼠皮下注射(每组4只，5组共20只)，1周后，转化细胞组的绝大部分裸鼠下背部皮下开始出现肿瘤，4周后所有4种不同转化细胞株接种的裸鼠全部长出大小不等的肿瘤，但非转化对照细胞于第5周后仍无一只裸鼠出现肿瘤。提示TEF-1β转基因转化细胞属恶性转化细胞，具有明显的致癌能力和致瘤作用。结论根据本研究结果及前期发现，可以认为新发现的TEF-1β是一个镉应答原癌基因。     

细胞周期素CyclinD1异常与肿瘤

CyclinD1是细胞周期调控中的重要分子,其基因和编码蛋白的异常与多种肿瘤的发生发展密切相关,本文从CyclinD1基因结构的改变和蛋白质表达的改变,论述其在肿瘤癌过程中与肿瘤相关基因协同作用的分子机制。     

TIF3转基因CHO和COS7细胞株的构建与鉴定

目的：TIF3（Mouse Translation Initiation Facfor 3)是从镉转化BALB／c-3T3细胞中克隆出来的新基因，其在基因文库（GenBank)的新添编号为AF271072。为了对该基因的生物学功能进行研究，构建了TIF3转基因CHO和COS7细胞株并作了鉴定。方法：采用磷酸钙介导转染技术和G418细胞筛选法，以pcDNA3.1/V5-His-TOPO为表达载体，构建TIF3转基因CHO和COS7细胞株；应用Western Blot技术对转基因表达产物进行分析与鉴定。实验设计分无转染组（空白对照）、载体转染组（载体对照）和目的基因转染组（载体＋TIF3cDNA)。结果：结果显示，无论在CHO细胞还是COS细胞，经转染和G418筛选后,无转染组的细胞100％死亡，而载体转染组和TIF3cDNA转染组的细胞形成较锪细胞集落。提示克隆化基因的细胞转染及G418筛选效果良好。经Western Blot分析与鉴定，在7株转染和经G418反复筛选的CHO细胞株中，有3株具有高效稳定表达约36kDa的TIF3编码蛋白质；在4株转染和经G418反复筛选的COS7细胞株中有2株也具有高效稳定的TIF3编码蛋白质表达，而无转染组和载体对照组的CHO和COS7细胞均缺乏此蛋白质表达。结论：本研究成功地构建了3株TIF3转基因CHO细胞株和2株TIF3转基因COS7细胞株。这两类TIF3转基因哺乳动物细胞稳定表达系统的建立，对今后的镉化物相关癌基因的发现及其生物学功能的研究具有重要的应用价值。     

镉相关新基因TIF3的蛋白表达与细胞转化功能研究

目的：探讨TIF3基因在镉细胞转化和致癌过程中的重要作用。方法：用细胞转染，Western blot，以及细胞转化等技术与方法，对克隆化基因TIF3的生物学功能进行研究。结果：TIF3cDNA以pcDNA3.1/V5-His-TOPO为表达载体所转染的CHO细胞和猴肾OCS1细胞均可表达分子量为36000的TIF3编码蛋白质，而非转染和单纯载体转染的对照细胞则无此蛋白表达；此外，TIF3cDNA转染NIH3T3细胞可导致TIF3蛋白质超额表达，并与细胞转化密切相关。结论：镉的细胞转化和致癌作用至少部分是因TIF3基因的高表达所致。     

TIF3镉应答基因的致癌性

[目的 ]前期研究发现 ,镉相关新基因TIF3 (基因文库添码 :AF2 710 72 )转染NIH3T3细胞可致其编码蛋白质表达升高而引起细胞转化。本研究的目的是对TIF3基因转化NIH3T3细胞的致癌能力和致瘤性进行鉴定。 [方法 ]软琼脂集落形成试验和裸鼠成瘤试验。 [结果 ]所有 4株不同的TIF3转染的NIH3T3细胞在软琼脂培养中均显示锚非依赖性生长能力 ,形成明显的细胞集落。而非转化对照细胞在软琼脂上则无生长能力。转化细胞和对照细胞分别给裸鼠皮下注射 (每组 4只 ) ,4周后所有接种转化细胞的裸鼠全部长出大小不等的肿瘤 ,但非转化的对照细胞于第 5周后仍无 1只裸鼠出现肿瘤。提示TIF3转基因转化细胞属恶性转化细胞 ,具有一定的致癌能力和致瘤作用。 [结论 ]根据本研究结果及前期发现 ,可以认为新发现的TIF3是一个镉应答原癌基因     

镍与多基因致癌作用

镍是人类生产、生活中的重要金属和人体必需微量元素，同时也是一种多系统、多器官、多细胞毒物。镍化合物已被确认为人类确证致癌物。许多报道认为：镍进入细胞后主要通过自由基作用、ＤＮＡ蛋白质交联及碱基甲基化等遗传、非遗传方式致癌［１５］。我们就镍致癌过程中的多基因变异研究进行回顾，为镍的分子致癌机制研究提供参考。一、镍与原癌基因的激活就其本质而言，原癌基因是一类编码关键性调控蛋白的正常细胞基因，对细胞的正常生长有极其重要的作用。当其发生突变或异常表达时，就成为导致细胞恶变的癌基因［６］。在镍的致癌机…     

P27、Skp2与肿瘤

肿瘤的发生是正常细胞染色体严重损伤的复杂过程，包括抑癌基因的失活，原癌基因的不正常激活，DNA转录表达失控，DNA损伤等。不论何种原因造成的细胞转化其最终表现均为细胞周期调控机制紊乱，分化受阻导致肿瘤发生。细胞周期受细胞周期蛋白（cyclin）、细胞周期蛋白依赖性激酶（CDK）以及其抑制剂（CKI）的共同调控。P27是一种新发现的CKI，P27的活性改变影响细胞周期过程，进而影响细胞的增殖。细胞S期激酶相关蛋白2（Skp2），     

RAS基因及表达产物P21在妇科肿瘤中的研究进展

Ｐ２１系由原癌基因ＲＡＳ家族（Ｋ－ｒａｓ，Ｈ－ｒａｓ，Ｎ－ｒａｓ）所编码的一种蛋白质，其分子量为２１ＫＤ，是细胞周期中重要的调控因子，当ＲＡＳ基因发生突变时，可以导致原癌基因激活，使Ｐ２１异常表达，参与肿瘤的发生和发展，本文就ＲＡＳ基因及其表达产物Ｐ２１在妇科肿瘤中的研究进展作了一综述。     

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 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.     

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.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.