Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
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PURPOSE
To develop a system for inducible photoreceptor-specific gene expression in transgenic mice. The tetracycline regulatory system was chosen because it possesses the useful property of direct control of gene expression through use of an exogenous agent, doxycycline, a tetracycline derivative.
METHODS
Transgenic mice were generated that carried the reverse tetracycline-controlled transactivator under the control of the photoreceptor-specific promoters for rhodopsin and interphotoreceptor retinoid-binding protein. These animals were crossed with transgenic mice carrying the lacZ reporter gene under control of the tetracycline operator cassette, creating doubly transgenic mice. Doxycycline was administered to induce expression of the reporter gene. Reporter assays were then performed to evaluate lacZ expression.
RESULTS
Doxycycline administration led to photoreceptor-specific expression of the lacZ reporter gene in the doubly transgenic mice. X-gal staining was restricted to photoreceptor inner segments and synaptic termini. Induction could be achieved by addition of the drug to the animals' drinking water or by intravitreal injection. Induction was noted within 24 hours of doxcycline administration. Because of variability among animals, there was an approximate correlation, but not a clean dose-response curve relating drug dose to level of reporter expression.
CONCLUSIONS
A transgenic system for inducible photoreceptor-specific gene expression has been developed. This system is currently being exploited to study the effects of regulated expression of genes of biological interest.
View on PubMed2000
2000
2000
OBJECTIVES
This study assessed the implementation of tobacco industry strategies to prevent a workplace smoking regulation.
METHODS
Tobacco industry internal documents were identified; hearing transcripts for the affiliations, arguments, and positions regarding the regulation of testifiers were coded; and media coverage was analyzed.
RESULTS
Tobacco industry strategies sought to increase business participation and economic discussions at public hearings and to promote unfavorable media coverage of the regulation. The percentage of business representatives opposing the regulation grew from 18% (5 to 28) to 57% (13 of 23) between the hearings. Economic arguments opposing the regulation rose from 25% (7 of 28) to 70% (16 of 23). Press coverage was neutral and did not increase during the period of the regulatory hearings.
CONCLUSIONS
The tobacco industry was successful in implementing 2 of its 3 strategies but was not able to prevent passage of the comprehensive workplace regulation.
View on PubMed2000
Biologically active interleukin (IL)-1beta is present in the pulmonary edema fluid obtained from patients with acute lung injury and has been implicated as an important early mediator of nonpulmonary epithelial wound repair. Therefore, we tested the hypothesis that IL-1beta would enhance wound repair in cultured monolayers from rat alveolar epithelial type II cells. IL-1beta (20 ng/ml) increased the rate of in vitro alveolar epithelial repair by 118 +/- 11% compared with that in serum-free medium control cells (P < 0.01). IL-1beta induced cell spreading and migration at the edge of the wound but not proliferation. Neutralizing antibodies to epidermal growth factor (EGF) and transforming growth factor-alpha or inhibition of the EGF receptor by tyrphostin AG-1478 or genistein inhibited IL-1beta-induced alveolar epithelial repair, indicating that IL-1beta enhances in vitro alveolar epithelial repair by an EGF- or transforming growth factor-alpha-dependent mechanism. Moreover, the mitogen-activated protein kinase pathway is involved in IL-1beta-induced alveolar epithelial repair because inhibition of extracellular signal-regulated kinase activation by PD-98059 inhibited IL-1beta-induced alveolar epithelial repair. In conclusion, IL-1beta augments in vitro alveolar epithelial repair, indicating a possible novel role for IL-1beta in the early repair process of the alveolar epithelium in acute lung injury.
View on PubMed2000