p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma

P16 and P14ARF are two tumor suppressors encoded by the locus ink4a-arf which is frequently deleted in human tumors. Recent experiments performed with mouse embryonic fibroblasts have shown that P14ARF is an upstream regulator of the P53 pathway. This raises the question as to whether in human tumors the loss of p14arf and mutation of p53 are mutually exclusive events which segregate with genetic alterations at other loci. To examine this question we performed a multigenic analysis on 29 gliomas. We analysed p53 and p14arf in relation with five other genetic loci encoding the most frequently mutated genes in human gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25-26. Our study shows for the first time that p53 mutations and p14arf deletions appear mutually exclusive in human glioblastoma, suggesting that they may be functionally redundant in glioma tumorigenesis. The P53 pathway is, therefore, disrupted in 81.8% of malignant gliomas (WHO grades III and IV), either by mutation of the p53 gene (31.8%) or by p14arf deletion (54.5%). These tumors further showed MDM2 overexpression (9.1%), egfr oncogene amplification/egfr overexpression (50%), pten mutations (27.3%) and loss of heterozygosity (LOH) at the chromosomal regions 10q23.3 (86.4%) and 10q25-26 (100%). These alterations did not segregate with p53 mutations or p14arf deletions, while p14arf and cdkn2a were always deleted.     

Integrating prenatal-postnatal smoking interventions into usual care in a health maintenance organization

Consistent with the increasing national emphasis on providing health promotion in clinical care settings, Stop Smoking for OuR Kids (STORK), a research-derived, prenatal-postnatal smoking cessation intervention, was implemented throughout prenatal clinics, inpatient postpartum services, and pediatric clinics of Kaiser Permanente Northwest. Process data collected during the project rollout and maintenance to monitor the clinical practices of clinicians and staff members, patient responses to the intervention, and penetration of the intervention into the health maintenance organization priority population of prenatal smokers high-lighted barriers to intervention delivery. These barriers fell into three categories related to the smoking intervention design, clinicians and staff members, and the organization. By monitoring the intervention implementation process, such problems were identified early. This allowed for implementing strategies to overcome many of these barriers and to assess their effectiveness. Keys to implementation success included simplifying the intervention activities, considering stakeholder needs, and providing tangible organizational resources and goals.     

Evaluation of serum cytokine and chemokine levels in dermatitis herpetiformis: a systematic review and meta-analysis

Immunologic Research -     

First example of familial posttransfusion purpura in two PlA1-negative sisters

Posttransfusion purpura (PTP) (platelet count 5000/microliter) was diagnosed in a female patient (never transfused, gravida IV, para IV) 1 week after transfusion for hysterectomy in 1978. She did not respond to pooled random-donor platelets but recovered following a single plasma exchange. Her platelets were PlA1 negative, and her plasma contained potent anti-PlA1. In 1986, her sister (never transfused, gravida III, para III) developed PTP (platelet counts 5-15,000/microliter) following surgery-associated transfusion. She did not respond to pooled random-donor platelets. Platelet-associated IgG was markedly elevated (5365) molecules/platelet; normal, less than 660); her plasma contained a potent platelet antibody with anti-PlA1 specificity. Her platelets were subsequently shown to be PlA1 negative. The platelet count did not rise above 30,000 per microliter, despite 3 days of high-dose methylprednisolone sodium succinate and 2 weeks of prednisone (80 mg/day). Later, her platelet count increased and remained normal after steroids were discontinued. The two sisters proved to be HLA-identical, and each possessed one haplotype carrying the DR3 marker, which has been implicated as a risk factor in neonatal alloimmune thrombocytopenia associated with anti-PlA1.     

The effectiveness of the Safety in Interventional Radiology (SIR) Shield in reducing droplet transmission and its effect on image quality and radiation dose

Objective:To evaluate the efficacy of a barrier shield in reducing droplet transmission and its effect on image quality and radiation dose in an interventional suite.Methods:A human cough droplet visualisation model in a supine position was developed to assess efficacy of barrier shield in reducing environmental contamination. Its effect on image quality (resolution and contrast) was evaluated via image quality test phantom. Changes in the radiation dose to patient post-shield utilisation was measured.Results:Use of the shield prevented escape of visible fluorescent cough droplets from the containment area. No subjective change in line-pair resolution was observed. No significant difference in contrast-to-noise ratio was measured. Radiation dosage to patient was increased; this is predominantly attributed to the increased air gap and not the physical properties of the shield.Conclusion:Use of the barrier shield provided an effective added layer of personal protection in the interventional radiology theatre for aerosol generating procedures.Advances in knowledge:This is the first time a human supine cough droplet visualisation has been developed. While multiple types of barrier shields have been described, this is the first systematic practical evaluation of a barrier shield designed for use in the interventional radiology theatre.     

构建大肠癌细胞相关基因Nrf3融合蛋白真核表达载体及其体外转染的初步功能分析

目的：应用基因芯片生物信息学分析思路筛查大肠癌细胞相关基因Nrf3，构建融合蛋白真核表达载体，检测其对体外转染癌细胞周期与凋亡的影响。方法：实验于2004—01／2006—07在南方医科大学病理解剖教研室及肿瘤研究所与中国农业大学农业生物技术国家重点实验室完成。①实验材料：大肠癌细胞组织及其配对的正常大肠黏膜各3例，由解放军总医院病理科提供：大肠癌LoVo细胞系由南方医科大学肿瘤研究所提供；肝癌SMMC7721细胞系由解放军军事医学科学院放射医学研究所提供；真核表达载体pEGFP-N1（Clontech公司）。②实验方法：分别应用Excel表、Affymetrix Microarray Suite Software5．0分析软件和STATA7．0分析软件，对基因芯片表达谱数据行交集补集分析、秩和检验及T检验，筛选“最重要的大肠癌细胞差异表达基因＆ESTs”，差异表达P〈0．05，差异倍数〉2。应用文献轮廓法进一步分析确定首选研究基因为Nrf3，提取组织样品总RNA，cDNA合成，PCR扩增产物经琼脂糖凝胶电泳分离后回收纯化，插入T载体中，SalⅠ和BamHⅠ双酶切后连接到pEGFP-N1载体．获得重组pEGFP-N1-Nrf3质粒。LoVo细胞在体外加入含体积分数为0．1小牛血清、100u／mL青链霉素的RPMI-1640培养基，置于37℃、体积分数为0．05的CO2饱和湿度培养箱中，待转染质粒pEGFP-N1-Nrf3与阴性对照质粒pEGFP-N1转染36h后，荧光显微镜观察候选基因亚细胞定位，FCM分选术观察其在体外对LoVo细胞周期和凋亡的影响。同法观察重组pEGFP-N1-Nrf3质粒体外转染对SMMC7721细胞周期和凋亡的影响。结果：①首选研究大肠癌细胞相关基因的确认：多种统计学方法分析获得最重要的大肠癌细胞相关基因17个，文献轮廓法进一步确认Nrf3为首选研究基因。②Nrf3基因表达：RT-PCR法检测Nrf3在3例大肠癌细胞组织均有表达，而在与其相配对的正常黏膜中表达较弱或不表达，与芯片检测结果基本一致；Nrf3在LoVo细胞中有表达。③Nrf3亚细胞定位：重组pEGFP-N1-Nrf3质粒转染的LoVo细胞其绿色荧光主要分布于细胞核内，提示Nrf3可能定位于细胞核内。（少Nrf3在体外对癌细胞周期与凋亡的影响：体外培养36h后与未转染LoVo细胞的空白对照比较，重组pEGFP-N1-Nrf3质粒转染的LoVo细胞S＋G2／M期所占比例明显减低，G2／M期下降尤为显著，G—G，期细胞所占比例明显增加。Nrf3转染作用于LoVo细胞后，未观察到明显“亚G1”峰（即凋亡峰）的出现。Nrf3体外转染的SMMC7721细胞周期及凋亡情况与LoVo细胞基本相似。结论：大肠癌细胞相关基因Nrf3在体外能够抑制LoVo细胞、SMMC7721细胞的DNA合成和有丝分裂，促使癌细胞阻滞于G0/G，期，抑制其生长增殖的同时不影响细胞凋亡，可作为大肠癌细胞候选分子标志物。     

Maternal smoking cessation and relapse prevention during health care visits

BACKGROUND: Although effects of maternal smoking during pregnancy could be alleviated if women quit early in pregnancy, most do not. Relapse rates among quitters are high. OBJECTIVE: To test the effects of a low-intensity, smoking-cessation/relapse-prevention intervention delivered by clinic staff and providers and based on stages-of-change constructs of the transtheoretical model and brief motivational interviewing techniques. METHODS: A quasi-experimental prospective cohort design employed in obstetric, in-patient, and pediatric care delivery settings of a large health maintenance organization in Portland, Oregon. Subjects were pregnant smokers registered for their first prenatal visit. Primary outcome measures were sustained (self-reported) quit rates during pregnancy and smoking abstinence between 6 and 12 months after delivery. RESULTS: Regression analyses found statistically significant improvement for intervention women in sustained pregnancy quit rates (OR=2.7, CI=1. 2-5.7) and on smoking abstinence between 6 and 12 months after delivery (OR=2.4, CI=1.1-5.3). CONCLUSIONS: While these outcomes are based on self-report only, they emerged despite variable delivery of the intervention across clinics and represent clinically meaningful improvements in rates of nonsmoking. The intervention supports women who want to quit smoking during pregnancy and improves the likelihood of their remaining nonsmokers for the long term.     

Intrathecal methotrexate overdose

We report two cases of intrathecal methotrexate overdose. A 3-y-old girl with acute lymphoblastic leukaemia and a 4-y-old boy with Burkitt's lymphoma were to receive an intrathecal injection of methotrexate after completion of intravenous methotrexate infusion. Instead of 12.5 mg, they both received a dose of 125 mg. Both children developed generalized convulsion 3 h after the overdose, but afterwards recovered completely. Intravenous folinic acid and dexamethasone rescue were employed, but no attempt was made to exchange the cerebrospinal fluid. In addition to the staffs failure to check the drug label carefully, the marked resemblance of the two dose preparations of methotrexate (50 mg/5 ml and 500 mg/5 ml) may have been contributory.