PubMed · 665648
A case of meconium ileus equivalent in a 30-year old man is presented. The pathology and therapy for the condition are discussed.
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R K Spiro, M E Landman. 1978. Meconium ileus equivalent.. https://pubmed.ncbi.nlm.nih.gov/665648/
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The platelet-derived growth factor beta-receptor undergoes polyubiquitination as a consequence of ligand binding. We have previously reported that ligand-induced ubiquitination of the receptor plays a negative regulatory role in its mitogenic signaling possibly by promoting the efficient degradation of the ligand-activated receptor (Mori, S., Heldin, C.-H., and Claesson-Welsh, L. (1993) J. Biol. Chem. 268, 577-583). In the present study, we have examined effects of different kinds of cell-penetrating proteasome inhibitors, including substrate-related peptidyl aldehydes, Cbz-Ile-Glu(O-t-Bu)-Ala-leucinal (where Bu is butyl and Cbz is benzyloxycarbonyl) (PSI) and Cbz-Leu-Leu-norvalinal (MG115), and a Streptomyces metabolite lactacystin, on degradation of the receptor in intact cells with the aim of evaluating the role of the receptor ubiquitination in the proteasome-dependent proteolytic process. These proteasome inhibitors were found to considerably inhibit ligand-stimulated degradation of the wild-type beta-receptor; however, their inhibitory effect was not observed when the cells expressing the ubiquitination-deficient mutant beta-receptor were analyzed. These data suggest that the degradation process of the ligand-stimulated beta-receptor involves the ubiquitin-proteasome proteolytic pathway.
N-Acetyl-L-cysteine (NAC) is an antioxidant precursor of intracellular glutathione (GSH), usually given in human as a mucolytic agent. In vitro, NAC and GSH have been shown to act on T cells by increasing interleukin (IL) 2 production, synthesis and turnover of IL-2 receptors, proliferation, cytotoxic properties, and resistance to apoptosis. We report here that NAC and GSH decrease in a dose-dependent manner human IL-4 production by stimulated peripheral blood T cells and by T helper (Th) 0- and Th2-like T cell clones. This effect was associated with a decrease in IL-4 messenger RNA transcription. In contrast, NAC and GSH had no effect on interferon gamma and increased IL-2 production and T cell proliferation. A functional consequence was the capacity of NAC and GSH to selectively decrease in a dose-dependent manner IL-4-induced immunoglobulin (Ig) E and IgG4 production by human peripheral blood mononuclear cells. Interestingly, NAC and GSH also acted directly on purified tonsillar B cells by decreasing the mature epsilon messenger RNA, hence decreasing IgE production. In contrast, IgA and IgM production were not affected. At the same time, B cell proliferation was increased in a dose-dependent manner. Not all antioxidants tested but only SH-bearing molecules mimicked these properties. Finally, when given orally to mice, NAC decreased both IgE and IgG1 antibody responses to ovalbumin. These results demonstrate that NAC, GSH, and other thiols may control the production of both the Th2-derived cytokine IL-4 and IL-4-induced Ig in vitro and in vivo.
AIM: Pilot study, examining the cardioprotective effect of an antioxidant regimen in patients with malignancies receiving high dose chemo- or radiotherapy. PATIENTS AND METHODS: 14 patients with chemotherapy and 10 patients with radiotherapy were randomized in a double-blind fashion (placebo versus vitamin E and C and N-acetylcysteine). Systolic and diastolic echocardiographic parameters were determined before and within three weeks of treatment completion. RESULTS: Left ventricular ejection fraction fell significantly in patients receiving placebo (radiotherapy: 67 +/- 6 to 56 +/- 2%, p = 0.008, chemotherapy: 67 +/- 7 to 60 +/- 8%, p = 0.05). Patients on antioxidants showed no significant fall in EF (radiotherapy: 63 +/- 8 to 61 +/- 7%, chemotherapy: 67 +/- 5 to 64 +/- 6%). CONCLUSION: The small number of patients in the study precludes a definitive statement. The preliminary results, however, suggest efficient cardioprotection by this cheap and safe antioxidant combination, so that larger studies are warranted for confirmation.