Atherosclerotic lesions form at distinct sites in the arterial tree, suggesting that hemodynamic forces influence the initiation of atherogenesis. If NF-B plays a role in atherogenesis, then the activation of this signal transduction pathway in arterial endothelium should show topographic variation. The expression of NF-B͞ IB components and NF-B activation was evaluated by specific antibody staining, en face confocal microscopy, and image analysis of endothelium in regions of mouse proximal aorta with high and low probability (HP and LP) for atherosclerotic lesion development. In control C57BL͞6 mice, expression levels of p65, IB␣, and IB were 5-to 18-fold higher in the HP region, yet NF-B was activated in a minority of endothelial cells. This suggested that NF-B signal transduction was primed for activation in HP regions on encountering an activation stimulus. Lipopolysaccharide treatment or feeding low-density lipoprotein receptor knockout mice an atherogenic diet resulted in NF-B activation and up-regulated expression of NF-B-inducible genes predominantly in HP region endothelium. Preferential regional activation of endothelial NF-B by systemic stimuli, including hypercholesterolemia, may contribute to the localization of atherosclerotic lesions at sites with high steadystate expression levels of NF-B͞IB components.atherosclerosis ͉ p65 ͉ IB␣ ͉ VCAM-1 ͉ E-selectin
Background: The objective is to provide surgical and pathological guidelines for radical prostatectomy (RP) with or without concurrent pelvic lymph node dissection (PLND) to achieve optimal benefit for patients, with minimal risk of harm. Methods:For surgical questions, a literature search of MEDLINE, EMBASE and the Cochrane database was performed. A literature search for the pathological questions was not conducted since the protocol for invasive carcinomas of the prostate gland developed by the College of American Pathologists (CAP) was endorsed. Urologists and pathologists were consulted for their assessment of the surgical and pathological recommendations. Results:Limited high-quality evidence from 95 primary studies was available and, therefore, the expert panel developed recommendations on the basis of a consensus of the expert opinion of the working group and through a consultation with urologists and pathologists. In addition to the CAP protocol, some technical recommendations related to the handling and processing of the specimen were made. Conclusion:Radical prostatectomy is recommended for the surgical treatment of prostate cancer, depending on a patient's preoperative risk profile. The panel unanimously determined that the goals for RP are to attain a positive margin rate of <25% for pT2 disease, a mortality rate of <1%, rates of rectal injury of <1% and blood transfusion rates of <10% in non-anemic patients. Standard PLND should be mandatory in high-risk patients, should be recommended for intermediate-risk patients and should be optional for low-risk patients. The quality and effectiveness of this treatment and of subsequent patient care depend on good management, effective communication and reporting between surgeons and pathologists working together as part of a multidisciplinary
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