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Hepatic processing of transforming growth factor beta in the rat. Uptake, metabolism, and biliary excretion. 总被引:21,自引:7,他引:14
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R J Coffey Jr L J Kost R M Lyons H L Moses N F LaRusso 《The Journal of clinical investigation》1987,80(3):750-757
Transforming growth factor beta (TGF beta), a recently discovered polypeptide, modulates growth of normal and neoplastic cells. Since little is known concerning in vivo disposition of TGF beta, we performed studies to examine the hepatic processing of biologically active 125I-TGF beta in the rat. After intravenous injection, 125I-TGF beta disappeared from the plasma with an initial t1/2 of 2.2 min; partial hepatectomy delayed the plasma disappearance of 125I-TGF beta by 80%. 60 min after intrafemoral injection, 63% of the recovered label was present in liver and/or bile; by 90 min, most of the label removed by the liver (83%) had been slowly excreted into bile. Nearly all the label in bile (96%) was soluble in trichloracetic acid and not immunoprecipitable by specific antiserum. Colchicine and vinblastine inhibited cumulative biliary excretion of label by 28 and 37%, respectively; chloroquine and leupeptin each increased the amount of label in bile that was precipitable by trichloracetic acid and that coeluted with authentic 125I-TGF beta on molecular sieve chromatography. There was efficient first-pass hepatic extraction of 125I-TGF beta (36%) in the isolated perfused rat liver, which was inhibited by unlabeled TGF beta (but not by epidermal growth factor, EGF) and by lectins in a dose-dependent manner; prolonged fasting also decreased clearance (26%). After fractionation of liver by differential or isopycnic centrifugation, radiolabel codistributed with marker enzymes for lysosomes. The results indicate rapid, extensive, inhibitable, and organ-selective extraction of TGF beta by the liver. After extraction, TGF beta undergoes efficient transhepatic transport, extensive intracellular metabolism, and slow but complete biliary excretion of its metabolites. Liver fractionation studies and pharmacologic manipulations suggest that these processes are associated with organelles that include microtubules and lysosomes. The data suggest that the liver is a major target tissue or site of metabolism for biologically active TGF beta. 相似文献
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Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. 总被引:13,自引:0,他引:13
P W Cook M R Pittelkow W W Keeble R Graves-Deal R J Coffey G D Shipley 《Cancer research》1992,52(11):3224-3227
Amphiregulin (AR) is a heparin-regulated, epidermal growth factor-like growth factor capable of stimulating the proliferation of non-tumorigenic cells while inhibiting cell proliferation in some human tumor cell lines in vitro. In the present study, we have investigated AR mRNA expression in normal, hyperproliferative, and neoplastic human epithelium. Our results demonstrate that, compared with the adjacent uninvolved epithelium, AR mRNA expression is markedly elevated in epidermal biopsies derived from three human psoriatic lesions as well as in biopsies derived from five human colon carcinomas and three human stomach carcinomas. Moreover, analysis of a colon carcinoma by in situ hybridization revealed that AR mRNA is localized to the epithelium. 相似文献
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D A Young M C McKee B Coffey S Cool N Roth R L Yolton 《Journal of the American Optometric Association》1988,59(5):364-371
Snellen letter and Vistech sine wave grating charts were used as refraction targets to determine differences in times required to accomplish subjective refractions, endpoint refractive values, and subject preferences. Thirty hyperopes and 30 myopes, divided into three age groups, were selected as subjects. Two examiners tested each subject using each chart. Both timed their subjective refractions and recorded their findings. After all data were recorded, each subject completed a questionnaire to determine chart preference. There were no clinically significant mean differences between the charts in terms of endpoint refractive data, but, on average, the Snellen chart was faster to use. Chart rating depended on the subject's refractive status with more myopes preferring the Snellen chart and more hyperopes rating the grating chart higher. 相似文献
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Howard S. Judelson Michael D. Coffey Felipe R. Arredondo Brett M. Tyler 《Current genetics》1993,23(3):211-218
A procedure for stable transformation was developed for Phytophthora megasperma f. sp. glycinea, an oomycete pathogen of soybean. Transformants were obtained using a bacterial hygromycin resistance gene fused to a promoter and terminator from the ham34 gene of another oomycete, Bremia lactucae. Vector DNA, alone or complexed to cationic liposomes, was introduced into protoplasts using polyethylene glycol and CaCl2. DNA and RNA hybridization, and phosphotransferase assays, confirmed the presence and expression of vector DNA in the transformants. Hybridization to electrophoretically separated chromosomes of P. m. glycinea showed that vector DNA had integrated into only one chromosome in four transformants, and into multiple chromosomes in one transformant. 相似文献