PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

BUILDING THE FOUNDATION OF EXCELLENCE IN HEART FAILURE NURSING

This column contains the presidential address presented during the Third Annual Meeting of the American Association of Heart Failure Nurses on June 28, 2007, in San Diego, California, titled "Building the Foundation of Excellence in Heart Failure Nursing."     

Relaxing retinotomies. Analysis of anatomic and visual results

The authors analyzed 100 consecutive eyes undergoing relaxing retinotomies to determine the anatomic and visual results associated with the use of this procedure. With a minimum follow-up of 6 months, 58 eyes were completely attached, 8 were partially attached (macula on), and 34 were detached. Thirty-four percent of all eyes and 50% of attached eyes obtained a visual acuity of 5/200 or greater at 6 months. At last examination, 29% of all eyes and 43% of attached eyes had a visual acuity of at least 5/200. Eyes that had circumferential relaxing retinotomies involving the entire temporal quadrant generally had lower visual acuities when compared with eyes that had relaxing retinotomies sparing the entire temporal quadrant. The use of a radial relaxing retinotomy also was associated with lower final visual acuity. The length of the relaxing retinotomy or the placement of the relaxing retinotomy either anterior or posterior to the encircling scleral buckle did not appear to influence the anatomic or visual results. Hypotony (intraocular pressure less than 5 mmHg) was seen in 43% of reattached eyes.     

Neoadjuvant chemotherapy in invasive bladder cancer: the evolving role of surgery

The role of an operation in patients receiving neoadjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder currently is evolving. An operation is essential for case selection and evaluation of local response but it also contributes to bladder preservation and survival. The procedure that is necessary to select for and assess response to chemotherapy may itself alter the actual or proceed to evolution of invasive bladder cancer. Neoadjuvant chemotherapy is a reasonable therapeutic strategy in selected patients but it remains to be seen whether the results will prove to be superior to those achieved with standard endoscopic and open operations.