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See detailTransferrin-Binding Protein B Of Neisseria Meningitidis: Sequence-Based Identification Of The Transferrin-Binding Site Confirmed By Site-Directed Mutagenesis
Renauld-Mongenie, G.; Lins, Laurence ULg; Krell, T. et al

in Journal of Bacteriology (2004), 186(3), 850-7

A sequence-based prediction method was employed to identify three ligand-binding domains in transferrin-binding protein B (TbpB) of Neisseria meningitidis strain B16B6. Site-directed mutagenesis of ... [more ▼]

A sequence-based prediction method was employed to identify three ligand-binding domains in transferrin-binding protein B (TbpB) of Neisseria meningitidis strain B16B6. Site-directed mutagenesis of residues located in these domains has led to the identification of two domains, amino acids 53 to 57 and 240 to 245, which are involved in binding to human transferrin (htf). These two domains are conserved in an alignment of different TbpB sequences from N. meningitidis and Neisseria gonorrhoeae, indicating a general functional role of the domains. Western blot analysis and BIAcore and isothermal titration calorimetry experiments demonstrated that site-directed mutations in both binding domains led to a decrease or abolition of htf binding. Analysis of mutated proteins by circular dichroism did not provide any evidence for structural alterations due to the amino acid replacements. The TbpB mutant R243N was devoid of any htf-binding activity, and antibodies elicited by the mutant showed strong bactericidal activity against the homologous strain, as well as against several heterologous tbpB isotype I strains. [less ▲]

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See detailPrognostic factors in patients with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. Groupe d'Etude des Neoplasies Endocriniennes Multiples (GENEM and groupe de Recherche et d'Etude du Syndrome de Zollinger-Ellison (GRESZE).
Cadiot, G.; Vuagnat, A.; Doukhan, I. et al

in Gastroenterology (1999), 116(2), 286-293

BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were ... [more ▼]

BACKGROUND & AIMS: Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients. METHODS: Data chart review was performed. RESULTS: Median follow-up was 102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (>/=3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03-1.14). CONCLUSIONS: Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them. [less ▲]

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