Publications
Department of Medicine faculty members published more than 3,000 peer-reviewed articles in 2022.
1994
1994
Acetaldehyde has been proposed as a mediator of fibrogenesis in alcoholic liver disease, based in part on its ability to stimulate collagen synthesis by hepatic lipocytes in late primary or passaged culture. In this study, we examined the effect of acetaldehyde on rat lipocytes and fibroblasts at various stages of culture, in an effort to determine whether culture-related events influence responsiveness to this compound. Lipocytes from normal rat liver were studied in primary culture at 3 and 7 days after plating; fibroblasts were studied in subculture, at subconfluent and confluent densities. Both cell types were incubated with 100 microM acetaldehyde for 24 hr followed by measurement of collagen synthesis and type I collagen gene expression. Acetaldehyde had no effect on lipocytes at either 3 or 7 days in primary culture. The inability of acetaldehyde to stimulate collagen synthesis in primary culture was not attributable to toxicity, because cell morphology and total protein synthesis were identical in both treated and untreated cultures. Fibroblasts exhibited a variable response to acetaldehyde that was dependent on cell density: subconfluent cells contained similar amounts of type I collagen mRNA in both the presence and absence of acetaldehyde, whereas confluent cells exhibited a 2- to 3-fold increase in collagen mRNA levels upon acetaldehyde exposure. To determine whether quiescent lipocytes would respond to acetaldehyde in a culture system that mimics the hepatic environment in vivo, lipocytes were plated in coculture with hepatocytes on a basement membrane gel and incubated with 20 mM ethanol for 72 hr. Direct communication between these two cell types did not provoke lipocyte activation, even in the setting of ethanol oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
View on PubMed1994
The signal transduction mechanism of the interleukin-2 receptor (IL-2R) remains largely undefined. The cytosolic domain of the IL-2R beta subunit is known to be essential for coupling to intracellular signaling pathways such as protein tyrosine kinase (PTK) and for control of IL-2 dependent cellular proliferation. A panel of cell lines that express IL-2R beta chains that contain sequential truncation mutations within the cytosolic domain were constructed. These cell lines were used to map the interaction of IL-2R with PTK activation, and the linkage of PTK function to activation of the enzyme phosphatidylinositol-3-kinase (Pl3K). The data show that the amino terminal segment of the acidic region (residues 314-350) within IL-2R beta is a critical site for PTK activation, and that activation of Pl3K is linked to IL-2 dependent tyrosine phosphorylation.
View on PubMed1994
Nurse practitioners with master's degrees were surveyed to assess the type and volume of occupational health services provided by primary care as compared with occupational health practitioners and the knowledge base in occupational health in these two groups. Thirty-six percent of 224 nonoccupational health nurse practitioners reported caseloads with 10% or more occupationally related chief complaints; 21% reported treating work-related injury or illness at least once per week. By contrast, a large percentage of nonoccupational health practitioners failed the knowledge-based exam. Large-scale prevention of occupational illness and injury warrants that primary care providers receive training in occupational health.
View on PubMed1994
The balance between detoxification and bioactivation of a compound in a particular species or organ is highly dependent on the relative amounts and activities of the different forms of cytochrome P450 (P450) that are expressed. Therefore, knowledge of the catalytic specificities and regulation of individual P450 forms is of paramount importance in predicting and/or rationalizing species, strain, and individual differences in xenobiotic metabolism as well as metabolic interactions between compounds, both endogenous and exogenous. The emergence in recent years of a battery of isoform-selective chemical inhibitors that can be used in vitro and in vivo in experimental animals and humans has greatly facilitated the identification of individual cytochromes P450 responsible for specific bioactivation and detoxification reactions. Many of these inhibitors are mechanism-based and owe their selectivity to metabolism by the target enzyme. Such compounds have also proven valuable as probes of the catalytic mechanism of cytochromes P450, for identifying amino acid residues of importance for the various functions of the enzyme, for assessing the physiological roles of P450-derived oxidation products of endogenous compounds, in chemical-induced models of acute hepatic porphyria, and for studying protein turnover. The identification of isoform-selective, nontoxic inhibitors of individual human cytochromes P450 raises the real possibility of modulation of human drug metabolism for therapeutic purposes.
View on PubMed1994
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