TY  - JOUR
A1  - Mansour, Ahmad M.
A1  - Arevalo, J. Fernando
A1  - Al Kahtani, Eman
A1  - Zegarra, Hernando
A1  - Abboud, Emad
A1  - Anand, Rajiv
A1  - Ahmadieh, Hamid
A1  - Sisk, Robert A.
A1  - Mirza, Salman
A1  - Tuncer, Samuray
A1  - Navea Tejerina, Amparo
A1  - Mataix, Jorge
A1  - Ascaso, Francisco J.
A1  - Pulido, Jose S.
A1  - Guthoff, Rainer
A1  - Goebel, Winfried
A1  - Roh, Young Jung
A1  - Banker, Alay S.
A1  - Gentile, Ronald C.
A1  - Alonso Martinez, Isabel
A1  - Morris, Rodney
A1  - Panday, Neeraj
A1  - Min, Park Jung
A1  - Merce, Emilie
A1  - Lai, Timothy Y. Y.
A1  - Massoud, Vicky
A1  - Ghazi, Nicola G.
T1  - Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma
JF  - Journal of Ophtamology
N2  - We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.
KW  - membrane
KW  - photodynamic therapy
KW  - secondary
KW  - bevacizumab
KW  - ranibizumab
KW  - patient
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117923
IS  - 210458
ER  - 
TY  - JOUR
A1  - Piteau, Marianne
A1  - Papatheodorou, Panagiotis
A1  - Schwan, Carsten
A1  - Schlosser, Andreas
A1  - Aktories, Klaus
A1  - Schmidt, Gudula
T1  - Lu/BCAM Adhesion Glycoprotein Is a Receptor for Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1)
JF  - PLoS Pathogens
N2  - The Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin which is a major virulence factor of pathogenic Escherichia coli strains. Here, we identified the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as cellular receptor for CNF1 by co-precipitation of cell surface molecules with tagged toxin. The CNF1-Lu/BCAM interaction was verified by direct protein-protein interaction analysis and competition studies. These studies revealed amino acids 720 to 1014 of CNF1 as the binding site for Lu/BCAM. We suggest two cell interaction sites in CNF1: first the N-terminus, which binds to p37LRP as postulated before. Binding of CNF1 to p37LRP seems to be crucial for the toxin's action. However, it is not sufficient for the binding of CNF1 to the cell surface. A region directly adjacent to the catalytic domain is a high affinity interaction site for Lu/BCAM. We found Lu/BCAM to be essential for the binding of CNF1 to cells. Cells deficient in Lu/BCAM but expressing p37LRP could not bind labeled CNF1. Therefore, we conclude that LRP and Lu/BCAM are both required for toxin action but with different functions. Author Summary We study a crucial virulence factor produced by pathogenic Escherichia coli strains, the Cytotoxic Necrotizing Factor 1 (CNF1). More than 80% of urinary tract infections (UTIs), which are counted among the most common bacterial infections of humans, are caused by Uropathogenic Escherichia coli (UPEC) strains. We and others elucidated the molecular mechanism of the E. coli toxin CNF1. It constitutively activates Rho GTPases by a direct covalent modification. The toxin enters mammalian cells by receptor-mediated endocytosis. Here, we identified the protein receptor for CNF1 by co-precipitation of cell surface molecules with the tagged toxin and subsequent Maldi-TOF analysis. We identified the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as receptor for CNF1 and located its interaction site to the C-terminal part of the toxin. We performed direct protein-protein interaction analysis and competition studies. Moreover, cells deficient in Lu/BCAM could not bind labeled CNF1. The identification of a toxin's cellular receptor and receptor binding region is an important task for understanding the pathogenic function of the toxin and, moreover, to make the toxin accessible for its use as a cellbiological and pharmacological tool, for example for the generation of immunotoxins.
KW  - laminin receptor
KW  - factor-I
KW  - toxin
KW  - RHO
KW  - cells
KW  - activation
KW  - protein
KW  - domain
KW  - translocation
KW  - membrane
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117987
SN  - 1553-7374
VL  - 10
IS  - 1
ER  -