University of Amsterdam

About: University of Amsterdam is a education organization based out in Amsterdam, Noord-Holland, Netherlands. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 59309 authors who have published 140894 publications receiving 5984137 citations. The organization is also known as: UvA & Universiteit van Amsterdam.

Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis.

Abstract: Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.

De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine

Abstract: Little is known about the signaling mechanisms that determine the highly regular patterning of the intestinal epithelium into crypts and villi. With the use of mouse models, we show that bone morphogenetic protein (BMP)-4 expression occurs exclusively in the intravillus mesenchyme. Villus epithelial cells respond to the BMP signal. Inhibition of BMP signaling by transgenic expression of noggin results in the formation of numerous ectopic crypt units perpendicular to the crypt-villus axis. These changes phenocopy the intestinal histopathology of patients with the cancer predisposition syndrome juvenile polyposis (JP), including the frequent occurrence of intraepithelial neoplasia. Many JP cases are known to harbor mutations in BMP pathway genes. These data indicate that intestinal BMP signaling represses de novo crypt formation and polyp growth.

Designing and evaluating e-business models

Abstract: This article presents an e-business modeling approach that combines the rigorous approach of IT systems analysis with an economic value perspective from business sciences.

Update on the Paris classification of superficial neoplastic lesions in the digestive tract

Abstract: Background and Study Aims: Neoplastic lesions in the digestive-tract mucosa are termed superficial when the depth of invasion is limited to the mucosa and submucosa. The endoscopic appearance has a predictive value for invasion into the submucosa, which is critical for the risk of nodal metastases. Materials and Methods: The endoscopic morphology of superficial lesions can be assessed with a standard video endoscope after spraying of a dye - an iodine-potassium iodide solution for the stratified squamous epithelium, or an indigo carmine solution for the columnar epithelium. In 2002, a workshop was held in Paris to explore the relevance of the Japanese classification. The conclusions were revised in 2003 in Osaka in relation to the definition of the subtypes used in endoscopy and the evaluation of the depth of invasion into the submucosa. In Japan, the description of advanced cancer in the digestive-tract mucosa using types 1 -4 is supplemented by a type 0 when the endoscopic appearance is that of a superficial lesion. Type 0 is divided into three categories: protruding (0-1), nonprotruding and nonexcavated (0-11), and excavated (0-III). Type 0-II lesions are then subdivided into slightly elevated (IIa), flat (IIb), or depressed (IIc). Nonprotruding depressed lesions are associated with a higher risk of submucosal invasion. After endoscopic resection, invasion into the submucosa is an important criterion for the necessity of additional surgical resection. Micrometer analysis of the depth of invasion in the specimen is more precise, and distinct cut-off limits have been established in the esophagus, stomach, and large bowel. Conclusions: The morphology of superficial and nonprotruding neoplastic lesions is relevant to the prognosis. Following endoscopic detection, the lesions are analyzed using chromoendoscopy and assigned a subtype of the type 0 classification. The choice between endoscopicorsurgical treatment is based on this description.