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."     

Adversity and working class vulnerability to minor affective disorder

In this paper, we examine the proposition that members of lower social classes are more likely than those from higher classes to develop minor affective disorders in the face of adverse experiences. This was examined using data from a psychiatric survey of the general population of Camberwell, S.E. London, U.K. Working class subjects experienced significantly more adversity than their middle class counterparts. However, the relationship between life events and psychiatric disorder was consistent and considerable in the working class group. It was attenuated or non-existent in middle class subjects, depending on the particular categorisation of the data. Log-linear analyses suggested that the basis of this finding was unclear. Both the results and the underlying reasons for them merit further investigation.     

The long-term outcome of head injury: Implications for service planning

As most of those experiencing traumatic brain injury tend to be young, disabled survivors will be gradually accruing in each locality as each year passes. How many need continuing care a decade after injury? How many need day care, or need help with finding work, or continuing support for carers? 190 patients who had been admitted to two UK regional neurosurgical units on average some 7 years earlier were followed up. With an average age of 29 years these patients stayed in hospital for an average 33 days. At follow-up 23% were classified as having moderate disability or worse on the Glasgow Outcome Scale, including 7.4% who had died subsequent to discharge. Survivors were given a neuropsychological assessment and a socioeconomic interview. Of the survivors, 17% had failed to make a good recovery, but 36% were failing to occupy their time in a meaningful way. Age over 30 at time of injury, not occupied before injury, and above-average length of stay were some of the predictors for failing to occupy time. Quality of life was severely curtailed for those who could not occupy their time, as was the case for their carers. Appropriate counselling, vocational evaluation and family support in the early years following injury may help to improve quality of life for both the head-injured person and their carers.     

A perspective on measurement of mutations in vivo.

The development of transgenic mouse lines with target genes that are suitable for tissue-specific mutagenesis studies is an important contribution to the field of environmental mutagenesis. These models can accommodate many of the questions relating to metabolism, distribution and relative potency of mutagens as well as providing a more comprehensive system for the identification of mutagens. However, the lesions that the field has learned about methods, development and validation from the use of in vitro systems must be applied to the development and validation of transgenic models.     

Immunopathology of glomerulonephritis associated with chronic woodchuck hepatitis virus infection in woodchucks (Marmota monax).

Retrospective analysis of necropsy findings of 705 woodchucks was performed to determine the prevalence and morphology of immune-mediated glomerulonephritis, its relationship to woodchuck hepatitis virus (WHV) infection, and the presence of major WHV antigens. Twenty-six woodchucks had glomerular lesions. Renal tissue of the 26 animals was evaluated histologically and immunohistochemically for immune-mediated glomerulonephritis. Of these 26 animals, immune-mediated glomerulonephritis was diagnosed in six, all of which were chronic WHV carriers. Membranous glomerulonephritis was identified in three animals, two of which also had mesangial proliferation. Host immunoglobulin was present within the mesangium and along capillary loops in all three. Woodchuck hepatitis virus core antigen (WHcAg) was present along capillary loops of two of these animals, one membranous and one mixed, and in the mesangium of all three. Woodchuck hepatitis virus surface antigen (WHsAg) deposition was similar to WHcAg deposition but was only present along capillaries in those animals with mixed nephritis. The remaining three animals had mesangial proliferation. WHsAg and host immunoglobulin deposition were predominately mesangial; WHcAg was not detected. Transmission electron microscopy showed thickening of the capillary loop basement membranes and subepithelial electron-dense deposits in animal one, and deposits in the mesangium in animal six.