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."     

Esophageal replacement with colon interposition in children.

During a 21-year period, 39 colon interposition operations were performed on 37 children at the UCLA Medical Center and the Childrens Hospital of Los Angeles. The average age at the time of operation was 5.8 years. The indications for operation were esophageal atresia in 23 patients and other benign strictures in 14 patients. The duration of patient follow-up ranged from 6 months to 21 years (mean: 9.7 years). The most common complications were esophagocolonic anastomotic leak (12), esophagocolonic anastomotic stricture (14), pneumonia, and pneumothorax. Fourteen of the 25 patients with retrosternal colon interposition had complications (56%), whereas 10 of 14 patients with left thoracic colon interposition had complications (71%). One patient died (mortality: 3%) after left thoracic interposition because of severe respiratory distress associated with other malformations. Each of the 18 patients with isoperistaltic colon interposition showed rapid transit and emptying, provided that obstruction or extensive dilatation did not occur; reverse colon segments were more dilated and emptied more slowly. The 25 patients with retrosternal colon segments had less colonic distension with better emptying than did the 14 patients with left thoracic interposition. Thirty-two of the 36 children increased their weight percentile after colon interposition. Within 2 years after cervical anastomotic stricture or leak, 78% of these children were asymptomatic and gaining weight. Thirty-one of the 37 patients (84%) had excellent results with colon interposition, with a mean follow-up of 9.7 years. Most of the major postoperative complications occurred within the first few weeks and were corrected during the first few months after operation. Preservation of the esophagus should be the surgeon's first priority; however, prolonged attempts to elongate the esophagus for anastomosis in certain patients with long-gap esophageal atresia have been more hazardous in our experience than has colon interposition.     

Preoperative care of infants with nephroblastoma. The International Society of Pediatric Oncology 6 experience.

The International Society of Pediatric Oncology (SIOP) recommends preoperative treatment in the management of eligible patients with Wilms' tumor. Until 1980, children younger than 12 months of age (infants) at diagnosis had been excluded from the SIOP trials. SIOP 6, conducted from 1980 to 1987, was the first SIOP study to include infants older than 6 months of age. This retrospective analysis of 145 infants registered to SIOP 6 demonstrates that in infants older than 6 months and having favorable histology (FH), a two-drug preoperative chemotherapy (CT) regimen of 4 weeks significantly ameliorated stage distribution as determined at delayed surgery but did not affect a good outcome. However, the CT dose utilized in SIOP 6 resulted in an unacceptable toxicity in this age group, and SIOP 9, the new SIOP study of Wilms' tumor, recommends a reduced dose of CT in infants. Preoperative CT is not recommended in infants younger than 6 months of age. Specifically, the high incidence (29%) of mesoblastic nephroma in this age group does not justify such an approach. Histopathologic diagnosis should be obtained in these patients before any treatment.