Search

Transforming growth factor-[alpha] (TGF-[alpha]) is a ligand for the EGF receptor (EGFR). EGFR activation is associated with fibroproliferative processes in human lung disease and animal models of pulmonary fibrosis. We determined the effects of EGFR tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) on the development and progression of TGF-[alpha]-induced pulmonary fibrosis. Using a doxycycline-regulatable transgenic mouse model of lung-specific TGF-[alpha] expression, we determined effects of treatment with gefitinib and erlotinib on changes in lung histology, total lung collagen, pulmonary mechanics, pulmonary hypertension, and expression of genes associated with synthesis of ECM and vascular remodeling. Induction in the lung of TGF-[alpha] caused progressive pulmonary fibrosis over an 8-wk period. Daily administration of gefitinib or erlotinib prevented development of fibrosis, reduced accumulation of total lung collagen, prevented weight loss, and prevented changes in pulmonary mechanics. Treatment of mice with gefitinib 4 wk after the induction of TGF-[alpha] prevented further increases in and partially reversed total collagen levels and changes in pulmonary mechanics and pulmonary hypertension. Increases in expression of genes associated with synthesis of ECM as well as decreases of genes associated with vascular remodeling were also prevented or partially reversed. Administration of gefitinib or erlotinib did not cause interstitial fibrosis or increases in lavage cell counts. Administration of small molecule EGFR tyrosine kinase inhibitors prevented further increases in and partially reversed pulmonary fibrosis induced directly by EGFR activation without inducing inflammatory cell influx or additional lung injury. gefitinib; erlotinib; pulmonary hypertension

In Gibson's Neuromancer, Riviera and Case serve as examples of two creators contrasted by Jean Baudrillard in 'Simulacra and Simulacrum': the specular, discursive representational artist, and the operational adept who efficiently codes the machines which perform work that until recently would have been performed by the specular, discursive imagination. Case and Riviera can be categorized, respectively, as magicians who practice what William Covino has called arresting and generative magic. Case is a cyberspace cowboy who steals or 'arrests' data, working for established power by operating technology, the brainchild of science and corporate power-two voices which constitute official knowledge. Riviera's holographic displays, on the other hand, recreate and disrupt the established flow of events as they are generated by the articulate powers around him. Baudrillard's four phases of the image mark a movement from arresting to generative magic, the most dynamic of these being the second, ripe for a simulation of crisis. The conflict between Molly and Riviera can be read as this kind, staged by the AIs, benefiting their final goal of unifying to become the matrix, that most adept of all generative magicians. Molly 'arrests' Riviera's power by paralyzing him with poison - a simulated death.

SINCE ITS FOUNDING IN 1929, THE MUSEUM OF MODERN ART IN NEW YORK HAS BEEN A BEACON OF MODERNISM, ACTING AS A SINGULAR advocate and home for some of the [...]