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.     

Psychiatric patients and their response to experimental stress

Serum levels of Epinephrine (E), norepinephrine (NE), heart rate (HR), skin conductance reaction (SCR) and skin conductance level (SCL) were measured in schizophrenic, endogenous depressed and anxiety patients as well as in normal controls. Conditions were rest, noise and a mental arithmetic (MA) task. Schizophrenic and depressed patients had an attenuated HR response to MA. Moreover, Schizophrenic patients also had higher NE base level and the highest NE secretion during noise. Anxiety and depressed patients showed significantly lower phasic electrodermal activity (SCR) throughout the whole trial, exclusively anxiety patients had significantly higher tonic electrodermal activity (SCL). These findings indicate that autonomous reactions discriminate between patient groups and controls as well as between each other.     

Visual versus computer evaluation of thiopental-induced EEG changes in temporal lobe epilepsy

Thiopental-induced EEG beta activity was analyzed both visually and by computer in 33 patients with complex partial epilepsy. Studies were done in 16 patients with depth electrodes in limbic structures and 17 patients with scalp and sphenoidal electrodes. The percentage of drug-induced change in beta activity was quantified by computer using spectral analysis. The statistical significance of asymmetries between homologous sites in the amount of change was determined. The spatial distribution of significant asymmetries was used for localization and compared with the results of independent visual analysis of the thiopental EEG. Concordance between computer and visual evaluation occurred in 10 of 17 scalp/sphenoidal and 10 of 16 depth electrode tests. The accuracy of visual and computer localization was determined by comparing them with locus of itcal EEG onset, interictal spikes, and positron emission tomography. In scalp/sphenoidal studies, computer analysis indicating asymmetry appeared more likely to correlate with independent clinical criteria than visual analysis. In depth studies the reverse appeared to be true. Scalp/sphenoidal tests yielded positive results in 25-30% of patients whereas depth electrode tests were positive in 50-70% of patients. The results indicate that computer analysis of surface thiopental tests is an accurate and useful supplement to visual evaluation of these tests.     

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."     

Tumor inhibiting properties of stereoisomeric [1,2-bis(3-hydroxyphenyl) ethylenediamine]dichloroplatinum(II)-complexes, Part II: Biological properties

The activity of stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine] dichloroplatinum(II)-complexes (1-PtCl2,R,S; 2-PtCl2, R,R/S,S; 3-PtCl2, R,R; 4-PtCl2, S,S) on several tumor models (MDA-MB 231 breast cancer cell line; P 388 leukemia, mouse; L 1210 leukemia, mouse; L 5222 leukemia, rat; Ehrlich ascites tumor, mouse--wildtype; cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.) is described. For comparison the analogous [1,2-bis(4-hydroxyphenyl)ethylendiamine]dichloroplatinum (II)-complexes (5-PtCl2, R, S; 6-PtCl2, R,R/S,S; 7-PtCl2, R,R; 8-PtCl2, S,S) and cisplatin are used. 1-PtCl2 to 4-PtCl2 (OH in 3,3'-positions) show their maximum antitumor effect at lower doses than 5-PtCl2 to 8-PtCl2 (OH in 4,4'-positions). 2-PtCl2 and 6-PtCl2 (R,R/S,S) are more active than 1-PtCl2 and 5-PtCl2 (R,S). 4-PtCl2 and 8-PtCl2 (S,S) are superior to 3-PtCl2 and 7-PtCl2 (R,R). On the L 5222 leukemia 2-PtCl2 (R,R/S,S), 4-PtCl2 (S,S) and 8-PtCl2 (S,S) markedly surpass cisplatin. Strong effects are produced by 2-PtCl2 to 4-PtCl2 on the Ehrlich ascites tumor (wildtype, cisplatin-, etoposide-, cyclophosphamide-, and daunomycin-resistant, resp.). The combination of 4-PtCl2 with cisplatin results in a weakly synergistic effect.     

Volar scaphotrapezial dislocation.

We present a case of volar luxation of the scaphotrapezial bone, in which radiographs suggested luxation of the scaphoid, but unclear relations to the other carpal bones. Computer tomographic reconstruction showed an isolated scaphotrapezial luxation. This was treated by closed reduction and a plaster cast, after which the patient regained normal function of her wrist.