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."     

Complications of orthodontic-orthognathic surgery treatment in mentally handicapped patients.

AIM: The aim of this study was to analyse possible intra- and postoperative complications and long-term results in combined orthodontic-orthognathic treatment of mentally handicapped patients compared with a control group of patients without handicap. PATIENTS AND METHODS: A group of 20 mentally handicapped patients (male = 7, female = 13) and of 102 non-handicapped patients (male = 36, female = 66) were evaluated retrospectively. The results of the two point-discrimination sensory test and the cephalometric findings of both groups were assessed. Complications during and after the operation, the results of nerve function tests and relapse rates were reported. The statistical analysis was carried out using binary logistical regression analysis with adjustment according to the diagnosis and the type of operation (p < 0.05) RESULTS: No significant differences could be found between the mentally handicapped and the non-handicapped patients. Only the nerve function test immediately postoperatively revealed differences between the two patient groups. The relapse rate in mentally handicapped patients was similar to non-handicapped patients. Forty-seven months after the operation, relapse (change in the ANB angle of more than 0.5 degrees ) was observed in four patients only (handicapped patients). CONCLUSION: Orthognathic surgical procedures in mentally handicapped patients can be carried out with a similarly high success rate as in mentally healthy patients.     

Dioxinlike components in incinerator fly ash: a comparison between chemical analysis data and results from a cell culture bioassay.

Potent polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxinlike polychlorinated biphenyls (PCBs) are among the most relevant toxic emissions from incinerators. Induction of cytochrome P450 1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity in mammalian cell culture (EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxinlike compounds. Fly ash extracts from municipal waste incinerators (MWI), a crematorium, wood combustors, and a noble metal recycling facility were analyzed in the EROD bioassay using rat hepatocytes in primary culture. Fractions containing 2,3,7,8-substituted PCDDs/PCDFs, dioxinlike PCBs, and 16 major polycyclic aromatic hydrocarbons (PAHs) were isolated from the extract and analyzed by gas chromatography-mass spectrometry (GC-MS) and by the EROD bioassay. It was found that with MWI samples the bioassay of the extract resulted in a two- to fivefold higher estimate of TCDD equivalents (TEQ) than the chemical analysis of PCDDs/PCDFs and PCBs. However, the outcome of both methods was significantly correlated, making the bioassay useful as a rough estimate for the sum of potent PCDDs/PCDFs and dioxinlike PCBs in extracts from MWI fly ash samples and in a fly ash sample from a crematorium. In noble metal recycling facility and wood combustor samples, higher amounts of PAHs were found, contributing to more pronounced differences between the results of both methods. The remaining unexplained inducing potency in fly ash samples probably results from additional dioxinlike components including certain PAHs not analyzed in this study.The hypothesis that emissions from MWI of hitherto unidentified dioxinlike compounds are higher by orders of magnitude than emissions of potent PCDDs/PCDFs and dioxinlike PCBs could not be confirmed. We found no indication for a marked synergistic interaction of dioxinlike fly ash components in the bioassay.     

Migratory, invasive and metastatic capacity of NCAM transfected rat glioma cells

A cDNA encoding a transmembrane 140 kDa isoform of the neural cell adhesion molecule, NCAM, was transfected into the rat glioma cell line BT4Cn. Transfectants with a homogeneously high expression of NCAM-B showed a decreased capacity for penetration of an artificial basement membrane when compared to cells transfected with expression-vector alone or untransfected cells. However, when injected subcutaneously into nude mice, both NCAM expressing cells and control cells produced invasive tumors. Nude mice injected with NCAM positive cells developed tumors with slower growth rates as compared to those induced by NCAM negative cells. This implies that NCAM may not only be involved in adhesive and motile behaviour of glioma cells, but also in their growth regulation.     

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.