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."     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

COMMUNITY PARTICIPATION OR COMMUNITY MANIPULATION? A CASE STUDY OF THE ILLAWARRA CANCER APPEAL-A-THON

Fashion parades, balls, raffles, and weekly deductions from thousands of workers' pay packets were integral to success of the Cancer Appeal-a-thon in the Illawarra region. In 1986–87 the Illawarra community was induced to contribute $1.5 million in order to purchase a linear accelerator for the Wollongong Hospital. The community agreed that a radiotherapy machine was the number one health service priority for the region. Or did it? Application of Alford's structural interests framework to this case-study reveals how failure to examine power relations between medical monopolizers, health care rationalizers and community participants results in an inability to recognise that alternative community needs — for cancer prevention, domiciliary care, or alternative therapies — might be unarticulated or unobservable, and in an inability to ask whether the community may be mistaken about, or unaware of, its own health needs. Specifically, the paper argues that, ‘community needs’ are easily manipulated or distorted by powerful interest groups and that the political context within which community needs are recognized, articulated and mobilized is the most important issue for community participation in the health policy-making process.     

Group A streptococcal septicaemia presenting as an acute abdomen in a child

We present an unusual case of group A streptococcal septicaemia referred to a paediatric surgical unit as acute appendicitis and highlight the importance of remembering this condition as part of a differential diagnosis.     

Creating a professional practice environment on a shoestring

Did you ever think, “If we just had a little money we could…”? The current health care environment is wrought with financial stressors that can be overwhelming and take up most of our time. Such stress can limit the development of a professional practice environment if you let it. How do you not only survive but thrive in this financial climate?     

The onset of tense marking in children at risk for specific language impairment.

PURPOSE: The purpose of this study was to develop and evaluate measures reflecting the onset of tense marking for children between the ages of 2;0 (years;months) and 3;0. METHOD: The validity of 4 cumulative measures of tense marker emergence and productivity was evaluated relative to existing measures of early grammatical development in a sample of 20 children followed longitudinally. Fourteen children were at risk for specific language impairment (AR-SLI group), and 6 children had low average language abilities (LA group). RESULTS: All measures of onset were highly correlated with the traditional measures; however, children's progress toward mastery of grammatical tense marking was best explained by the productivity of their tense marking systems. Finally, the onset measures imposing productivity requirements best differentiated children in the LA group from those in the AR-SLI group. CONCLUSIONS: The clinical implications for using the late onset of tense marking to improve the early identification of SLI are discussed.