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Capsule endoscopy in pediatrics: A 10-years journey

World Journal of Gastroenterology 2014年第44期20卷 16603-16608页

作者： Salvatore Oliva stanley A cohen Giovanni Di Nardo Gianfranco Gualdi Salvatore Cucchiara Emanuele Casciani Department of Pediatrics Pediatric Gastroenterology Unit Sapienza University of Rome Children’s Center for Digestive Health Care Radiology DEA Sapienza University of Rome University Hospital Umberto I

Video capsule endoscopy (CE) for evaluation the esophagus (ECE), small bowel (SBCE) and the colon (CCE) is particularly useful in pediatrics, because this imaging modality does not require ionizing radiation, deep sedation or general anesthesia. The risk of capsule retention appears to be dependent on indication rather than age and parallels the adult experience by indication, making SBCE a relatively safe procedure with a significant diagnostic yield. The newest indication, assessment of mucosal change, greatly enhances and expands its potential benefit. The diagnostic role of CE extends beyond the SB. The use of ECE also may enhance our knowledge of esophageal disease and assist patient care. Colon CCE is a novel minimally invasive and painless endoscopic technique allowing exploration of the colon without need for sedation, rectal intubation and gas insufflation. The limited data on ECE and CCE in pediatrics does not yet allow the same conclusions regarding efficacy; however, both appear to provide safe methods to assess and monitor mucosal change in their respective areas with little discomfort. Moreover, although experience has been limited, the patency capsule may help lessen the potential of capsule retention; and newly researched protocols for bowel cleaning may further enhance CE’s diagnostic yield. However, further research is needed to optimize the use of the various CE procedures in pediatric populations.

关键词： Capsule endoscopy Children Small bowel Pediatric endoscopy

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Bidirectional effect of Wnt signaling antagonist DKK1 on the modulation of anthrax toxin uptake

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Science China(Life Sciences) 2014年第5期57卷 469-481页

作者： QIAN LiLi CAI ChangZu YUAN PengFei JEONG Sun-Young YANG XiaoZhou DEALMEIDA Venita ERNST James COSTA Michael cohen stanley N. WEI WenSheng College of Life Sciences and State Key Laboratory of Protein and Plant Gene Research Peking University Department of Genetics Stanford University School of Medicine Department of Cancer Targets GenentechInc.South San Francisco Department of Protein Chemistry and Protein Engineering GenentechInc.South San Francisco Department of Medicine Stanford University School of Medicine

LRP6, a co-receptor for the morphogen Wnt, aids endocytosis of anthrax complexes. Here we report that Dickkopfl （DKK1） protein, a secreted LRP6 ligand and antagonist, is also a modulator of anthrax toxin sensitivity, shRNA-mediated gene silencing or TALEN-mediated gene knockout of DKK1 reduced sensitivity of cells to PA-dependent hybrid toxins. However, unlike the solely inhibitory effect on Wnt signaling, the effects of DKK1 overexpression on anthrax toxicity were bidirectional, depending on its endogenous expression and cell context. Fluorescence microscopy and biochemical analyses showed that DKK1 facilitates internalization of anthrax toxins and their receptors, an event mediated by DKK1-LRP6-Kremen2 complex. Monoclonal antibodies against DKK1 provided dose-dependent protection to macrophages from killing by anthrax lethal toxin （LT）. Our discovery that DKK1 forms ternary structure with LRP6 and Kremen2 in promoting PA-mediated toxin internalization provides a paradigm for bacterial exploitation of mechanisms that host cells use to internalize signaling proteins.

关键词： DKK1 anthrax toxin LRP6 TALENs internalization Kremen2 receptor Wnt

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Enemy at the Gates:It's Not Only About Anthrax

Enemy at the Gates:It's Not Only About Anthrax

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者：魏文胜 stanley cohen School of Life.Sciences Peking University Department of Genetics Stanford University School of MedicineStanfordCA 94305

Anthrax is a lethal disease caused by Bacillus anthracis,a gram-positive and sporeforming *** bacterium exerts its toxic,effect by secreting out three proteins, PA(protective antigen),LF(lethal factor), and EF(edema factor).Since we identified LRP6,a cell surface receptor protein involved in Wnt-signaling pathway,as the co-receptor for anthrax toxin lethality,heated debate on whether LRP6 plays an essential role in anthrax toxin internalization has never been *** controversial results have been reported from different groups,arguing about the exact role of LRP6 in anthrax toxicity. We have recently identified several other components in Wnt-signaling pathway involved in anthrax *** we report our recent study on DKK1,an antagonist of LRP6 and a Wnt signaling *** of DKK1 expression through shRNA inhibition led to elevated level of cellular resistance to anthrax,demonstrating the active role of DKK1 in anthrax ***,three out of seven monoclonal antibodies against this protein are able to protect RAW264.7 cells from anthrax toxin *** addition, effect of DKK1 on cell sensitivity to toxin depends on LRP6 expression,suggesting a model that LRP6 and DKK1 work together to facilitate the endocytosis process of the toxin, and reinforcing the role of LRP6 in this infection ***,both LRP6 and DKK1 were found to be engaged in PE (Pseudomonas exotoxin A) toxicity,implying the potential involvement of Wnt components in a broad spectrum of bacterial infection pathways.

关键词： Infection LRP6 Toxin Internalization

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表皮生长因子

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世界科学 1988年第7期 12-15页

作者： stanley cohen 傅杰青

斯坦利·科恩在50年代初曾经是丽塔·蒙塔尔奇尼在研究神经生长因子(NGF)方面的助手,但是他在研究NFF的过程中发现了NGF所解释不了的生长因子:他紧追不放,终于发现了表皮生长因子(EGF)。作为生化学家,在将近30年的时间里他在生化和细胞... 详细信息

斯坦利·科恩在50年代初曾经是丽塔·蒙塔尔奇尼在研究神经生长因子(NGF)方面的助手,但是他在研究NFF的过程中发现了NGF所解释不了的生长因子:他紧追不放,终于发现了表皮生长因子(EGF)。作为生化学家,在将近30年的时间里他在生化和细胞水平上系统地研究了EGF及其受体,并因之与蒙塔尔奇尼分享了1986年生理学或医学诺贝尔奖。尽管NGF与EGF还没有在应用方面显露其重要作用,但确实开辟了生物学的新领域。

关键词： EGF 蛋白激酶生理学尿抑胃素丙酮酸激酶基础医学表皮生长因子磷酸化生物学效应受体

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