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Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.  相似文献   
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Polyclonal antibodies recognizing the pyridyloxobutyl (POB) moiety of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were produced in rabbits immunized either with POB-bovine albumin or POB-Sepharose. The POB intermediates necessary to modify the protein were generated by alkaline (pH 9.0) treatment of the synthetic precursor 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone. In a competitive enzyme linked immunoabsorbent assay (ELISA), 70 pmole NNK inhibited 50% of the binding of the anti-POB antibodies to POB-protein absorbed on microtiterplates. This 50% inhibition varied from 70 pmole to 200 nmole using a series of NNK analogues, depending on the integrity of the POB moiety. Immunological techniques initiated in this study detect NNK-protein conjugates or measure the quantity of POB groups liberated upon alkaline or acid treatment of NNK modified protein.  相似文献   
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Familial adenomatous polyposis (FAP) is characterized by the presence of premalignant adenomas of the large and small bowel. Prophylactic colectomy deals with the risk for colon cancer, leaving duodenal cancer as the leading cause of death. Although most FAP patients have duodenal adenomas, only approximately 5% develop duodenal cancer. This study looks at progression of duodenal polyps with time. The outcome of endoscopic surveillance in the duodenum of 70 patients with familial adenomatous polyposis was determined. A mean of 40 months elapsed between endoscopies. Outcome was measured using video comparison and a staging system that includes histological assessment. Duodenal cancer developed in one patient, and was suspected in two others. The stage of duodenal polyposis worsened in another seven patients. When histology was ignored, comparison of video recordings in 52 patients showed a worsening in 21 (40%). In conclusion, further surveillance appears warranted so that patients at high risk for duodenal cancer might receive early treatment. Should slow progression of duodenal polyposis be shown to be associated with low risk, then most patients can be safely offered less frequent endoscopies than hitherto.  相似文献   
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This study has demonstrated the involvement of multiple forms of rat hepatic microsomal CoA ligases in the formation of 2-arylpropionyl-CoA thioesters. In the presence of (-)R-ibuprofen (0.1 microM-1 mM) two enzymic processes were observed, one of which exhibited enantiospecificity and apparent high affinity for the R enantiomer (Km 0.06 microM) whilst the second, a low-affinity component was non-enantiospecific. An equivalent high-affinity isoform catalysing R-flurbiprofen-CoA formation at concentrations less than 100 microM was not demonstrated. However, at higher substrate concentrations formation of both R- and S-flurbiprofenyl-CoA thioesters occurred. Marked inter-individual variation was observed in the formation of S-ibuprofen-CoA and S-flurbiprofen-CoA in the rats studied.  相似文献   
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Two additional cases of Peutz-Jeghers syndrome are described. One of them, a 19 year-old female, is a sporadic case, whereas in the other case, also a 19 year-old female, there are two members of the family with the Peutz-Jeghers syndrome. A review of some salient features of this entity is made. These include clinical presentation, histopathological features, malignant potential and treatment.  相似文献   
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