Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer.

The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer.     

P55Nordic Occupational Skin Questionnaire (NOSQ‐2002)

Questionnaire‐tools for surveying occupational skin diseases and exposure are needed for comparable epidemiological research, workplace assessments, and evaluation of workplace interventions. The Nordic Occupational Skin Questionnaire Group supported by the Nordic Council of Ministers has developed a standardized questionnaire‐tool for surveys on work‐related skin diseases and skin exposures to environmental factors.
Nordic Occupational Skin Questionnaire (NOSQ‐2002) includes two questionnaires designed for separate purposes. NOSQ‐2002/short is a 4‐page questionnaire for screening skin problems at workplaces. NOSQ‐2002/long is an in‐depth survey tool for research purposes. The questionnaire covers occupational history, atopic symptoms, self‐reported hand or forearm eczema, exacerbating factors, consequences and life impact of dermatoses, self‐reported contact urticaria on hands or forearms, skin symptoms, skin tests, exposures, and protective glove use. For the time being, NOSQ‐2002 is available in English, Danish, Swedish, Finnish and Icelandic. Further translations are welcomed.
The NOSQ‐2002 report includes a review of pertinent literature on questionnaire methods for skin disease studies. Questions on work and exposure can be tailored to specific populations or occupational groups, according to the instructions and recommendations given in NOSQ‐2002/INFO version of the questionnaire.
The NOSQ‐2002 questionnaire files can be downloaded from http://www.ami.dk /NOSQ. The Nordic Council of Ministers has the copyright to the NOSQ‐2002 questionnaires. Use of the questionnaires is free of charge. The NOSQ‐2002 questionnaires and their present and possible future translations cannot be used commercially.     

Scedosporium endophthalmitis: two fatal disseminated cases of Scedosporium infection presenting with endophthalmitis

The incidence of disseminated infection with Scedosporium species is increasing in patients with haematological malignancy. Two fatal cases are reported of patients with acute myeloid leukaemia and neutropenia who presented with Scedosporium endophthalmitis. Diagnosis of fungal infection was delayed as blood and vitreous cultures were positive only after 3 days in patient 1 and blood culture was positive at 7 days in patient 2. Despite antifungal therapy with amphotericin B and additional fluconazole in patient 2, both patients died of overwhelming fungal septicaemia. Post‐mortem examination of the right globe in patient 1 showed haemorrhagic necrotizing chorioretinitis with numerous fungal hyphae in choroidal vessels, choroid, retina and vitreous. Scedosporium species are often resistant to conventional antifungal therapy including amphotericin B. Diagnosis is difficult and mortality in disseminated infection is high.     

瘢痕疙瘩发病机制的研究动态

目的:总结瘢痕疙瘩在分子遗传学和生物化学方面的发病机制,为临床诊断和治疗提供可靠的依据。资料来源:应用计算机检索Pubmed1980-01/2006-10相关瘢痕疙瘩发病机制方面的文献,检索词“keloids”,限定文献语言种类为English。同时计算机检索中国期刊网1980-01/2006-10相关瘢痕疙瘩发病机制方面的文献,检索词“瘢痕疙瘩”,限定文献语言种类为中文。资料选择:对资料进行初审,选取包括瘢痕疙瘩发病机制的文献,开始查找全文。纳入标准:与瘢痕疙瘩和瘢痕疙瘩成纤维细胞相关的分子生物学研究。排除标准:相关的综述文献。资料提炼:共检索到681篇关于瘢痕疙瘩发病机制的文献,最终纳入33篇符合标准的文献。资料综合:瘢痕疙瘩有着过度生长、侵犯邻近组织、手术切除后极易复发、治疗效果不佳等特点,成为当今医学界面临的一个重大难题。瘢痕疙瘩发病机制迄今未明,本文从遗传机制、成纤维细胞功能、生物活性因子和胶原代谢等方面综述了近几年来对瘢痕疙瘩病因研究的最新进展,发现利用基因检测技术成为探求病因的一个重要手段和发展趋势,也为未来基因治疗提供了可靠的实验室依据。结论:越来越多的研究在瘢痕疙瘩相关致病基因位点的定位和克隆方面展开,这不但能够查找出发病原因,还可以为易感人群的早期预防提供方向,为瘢痕疙瘩的基因治疗奠定一定的基础。     

NURR1基因修饰C17.2神经干细胞移植治疗脑梗死

目的:比较C17.2神经干细胞和NURR1基因修饰的C17.2神经干细胞移植治疗对脑梗死模型鼠神经功能缺损的改善效果,观察细胞移植后与宿主脑组织的整合、存活、移行及分化情况。方法:实验于2005-06/12在中山大学附属第二医院林百欣实验中心完成。①实验材料:选取清洁级健康SD雄性大鼠78只,随机数字表法分为模型对照组、神经干细胞组、转基因神经干细胞组,26只/组。条件永生化神经干细胞系C17.2由哈佛大学儿童医院Even Synder教授惠赠。pAdeasy-NURR1重组复制缺陷性腺病毒由本实验室成功构建。Dil18荧光染料(Chemicon公司产品)。②实验方法:收集C17.2神经干细胞和pAdeasy-NURR1 C17.2神经干细胞,各分为两管,一管加入Dil18荧光示踪剂。各组大鼠均采用线栓法建立局灶性脑缺血/再灌注损伤模型,3d后进行细胞移植,以江湾Ⅱ型脑立体定向仪进行立体定位,选择缺血半暗区3个位点为移植区:前囟头侧1mm,旁开2mm,深度1.2mm;前囟尾侧3mm,旁开1.5mm,深度1.2mm;前囟尾侧6mm,旁开2mm,深度1.2mm。模型对照组每位点注射单纯培养液2μL;神经干细胞组取6只每位点移植Dil18标记的C17.2神经干细胞悬液2μL,剩余20只每位点移植C17.2神经干细胞悬液2μL;转基因神经干细胞组取6只每位点移植Dil18标记的pAdeasy-NURR1 C17.2神经干细胞悬液2μL,余20只每位点移植pAdeasy-NURR1 C17.2神经干细胞悬液2μL。③实验评估:各组大鼠分别在移植前1d及移植后1周、2周、1个月进行神经功能缺损评分。移植后1周、2周、1个月进行荧光示踪检查及神经元特异烯醇化酶免疫组化检测。移植后6个月行组织学检查。结果:移植后1周,模型对照组死亡1只,神经干细胞组死亡2组,转基因神经干细胞组死亡2只,均淘汰并予以补充。①神经功能缺损评分:移植前1d各组大鼠神经功能缺损评分基本相似(P>0.05)。移植后1周、2周、1个月神经干细胞组、转基因神经干细胞组神经功能缺损评分均明显低于模型对照组(P<0.05);转基因神经干细胞组下降趋势较神经干细胞组更为显著(P<0.05)。②Dil18荧光细胞示踪结果:移植后1周荧光示踪细胞主要在针道内,少数细胞开始移行至周围神经组织。移植后2周,细胞移行至更远距离,并明显向梗死灶方向移行,细胞有突触样结构与周围细胞形成联系。移植后1个月细胞向周围扩散,甚至在远隔部位也可见荧光细胞。③神经元特异烯醇化酶免疫组化检测结果:移植后2周、1个月,转基因神经干细胞组神经元特异烯醇化酶阳性细胞数均明显高于神经干细胞组(P均<0.05)。④细胞组织学检查:移植后6个月,各组大鼠注射针道周围脑组织仍呈正常的层次和结构,未见有明显异型细胞增生。结论:①NURR1基因修饰的C17.2神经干细胞移植治疗局灶性脑梗死能显著改善神经功能缺损,效果优于C17.2神经干细胞。②移植后供体细胞存活并向注射针道周围神经组织移行,促进神经干细胞向神经元方向的分化。     

瘢痕疙瘩家系Fas基因的突变：2个家系10份标本分析

目的:观察瘢痕疙瘩家系样本中Fas基因有无突变,探讨Fas基因突变在瘢痕疙瘩形成中的意义。方法:实验于2005-01/05在上海基康公司完成。①标本来自南方医科大学南方医院整形外科2005年收集的A和B两个瘢痕疙瘩家系,所有参与观察的家系成员均签署知情同意书。②采用聚合酶链反应及基因测序技术,分别以A家系两例患者的瘢痕疙瘩组织为观察对象,以其周围正常皮肤及外周静脉血作为自身对照;其配偶的外周静脉血作为正常对照。并以B家系中两例患者的外周静脉血作为不同家系间的对照。共取10份样本,4份组织样本,6份静脉血标本。检测10份样本中Fas基因外显子1～9的基因序列。结果:①基因测序发现所检测的10个瘢痕疙瘩家系标本Fas基因的1～8外显子均未发现突变。②2份瘢痕疙瘩组织标本在第9外显子编码区的11bp,53bp两个位点上存在单个碱基的基因突变或多态性改变。结论:瘢痕疙瘩Fas基因外显子9区段的基因结构异常极有可能造成Fas蛋白的功能改变,从而导致身体局部瘢痕疙瘩的形成。