Therapeutic targeting of cathepsin C::from pathophysiology to treatment

Cathepsin C (CatC) is a highly conserved tetrameric lysosomal cysteine dipeptidyl aminopeptidase. The best characterized physiological function of CatC is the activation of pro-inflammatory granule-associated serine proteases. These proteases are synthesized as inactive zymogens containing an N-terminal pro-dipeptide, which maintains the zymogen in its inactive conformation and prevents premature activation, which is potentially toxic to the cell. The activation of serine protease zymogens occurs through cleavage of the N-terminal dipeptide by CatC during cell maturation in the bone marrow. In vivo data suggest that pharmacological inhibition of pro-inflammatory serine proteases would suppress or attenuate deleterious effects of inflammatory/auto-immune disorders mediated by these proteases. The pathological deficiency in CatC is associated with Papillon-Lefèvre syndrome. The patients however do not present marked immunodeficiency despite the absence of active serine proteases in immune defense cells. Hence, the transitory pharmacological blockade of CatC activity in the precursor cells of the bone marrow may represent an attractive therapeutic strategy to regulate activity of serine proteases in inflammatory and immunologic conditions. A variety of CatC inhibitors have been developed both by pharmaceutical companies and academic investigators, some of which are currently being employed and evaluated in preclinical/clinical trials

Letter from Mellon National Bank, Pittsburgh, Pennsylvania, to First National Bank, Birmingham, Alabama, June 1, 1909

This item is from the Woodward Family Papers. The papers span four generations and include business and personal correspondence, financial records, photographs, and other materials of this Birmingham, Alabama family which operated the Woodward Iron Company

Listing BRICs: Stock Issuers from Brazil, Russia, India, and China in New York, London, and Luxembourg

In the past decade, hundreds of companies from emerging markets have listed their shares on American and European stock markets. Brazil, Russia, India, and China (BRIC) are the main countries of origin of issuers, and stock exchanges in the United States, the United Kingdom, and Luxembourg are the main destinations involved in the process. We use a comprehensive data set for these home and host markets for the end of 2008 to explore the intensity of foreign listings, the subnational geography of cross-listed firms, and the destinations of foreign listings. Cross-listing firms tend to be relatively large and come from capital-intensive, export-oriented, and high-growth sectors. Trading links with and industrial specialization of the host markets affect the choice of destination markets. These patterns, however, are not universal across countries. There is a high concentration of cross-listed firms in the leading financial centers of the BRIC countries, particularly in Russia and Brazil. Firms outside of the leading centers rarely cross-list, and when they do, they enter second-tier host markets. While BRIC countries have a large potential for further foreign listings, the process remains politically sensitive. Our results highlight the shortcomings of the literature on cross-listing in economics and the significance of the cross-listing phenomenon to future research in financial geographies. Copyright (c) 2010 Clark University.