Cytokines are thought to contribute to the induction of pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. The molecular mechanisms that underlie beta-cell death were investigated by studying cytokine-induced cell death in beta-cell lines. A combination of three cytokines (interleukin-1 beta, tumour necrosis factor-alpha, and interferon-gamma) induced apoptotic cell death in the mouse pancreatic beta-cell line beta TC1, as judged from the appearance of cells with hypodiploid nuclei and oligonucleosomal DNA fragmentation. The same treatment also induced apoptosis in the mouse pancreatic alpha-cell line alpha TC1 and the NOD/Lt mouse beta-cell line NIT-1, although to a lesser extent than in beta TC1 cells. The abundance of endogenous Bcl-2 in beta TC1 cells was lower than that in the other two cell lines. Overexpression of human Bcl-2 in beta TC1 cells partially protected them from cytokine-induced cell death. These results suggest that apoptosis may be responsible, at least in part, for cytokine-induced beta-cell destruction and that Bcl-2 prevents apoptosis in pancreatic islet cells.
SummaryTwo-site immunoradiometric assay for serum ferritin was developed by anti-human liver ferritin antiserum applied on polyvinyl V bottom microtiter plates. The coefficient of variation was 4.4-5.9% of liver ferritin dissolved in 1/4 diluted human serum at a concentration of 0.625-125ng/ml. The lowest concentration (0.625ng/ml) was statistically distinguishable from the background by Student's t test (p<0.05). Isoferritin patterns of serum ferritin and tissue ferritins were examined by the combination of gel isoelectric focussing and 2-site immunoradiometric assay in order to explore any similarities in pIs within these ferritins. Although serum ferritin had wide range of pIs, its basic isomers corresponded well to those of liver and spleen ferritin. Geometric means and their 95% confidence limits in serum ferritin concentration were 70 ng/ml and 12-411ng/ml, respectively, in sera of 205 healthy males (16-25 years), and 12ng/ml and 1-211ng/ml, respectively, in 421 healthy females (16-59 years). Keywords serum ferritin, isoferritin, anti-human liver ferritin, immuno radiometric assay, gel isoelectric focussing, p1, liver ferritin Ferritin is a high molecular weight iron-containing protein, which is distributed intracellularly in many tissues and can frequently be found by conventional methods in the sera of patients with certain liver diseases (1). However, recent progress in immunoradiometric assay disclosed it as a common component of all sera (2-6) and showed its parallel relation to the amount of storage iron (1,4,(7)(8)(9). Accordingly, serum ferritin concentration has drawn attention as being a reliable indicator in evaluating iron nutrition. The present study describes a modification of 2-site immunoradiometric assay for ferritin using polyvinyl V-bottom microtiter plates (10) coated by anti-human liver ferritin antiserum as an immunoadsorbent, and discusses the rationality of the antiserum 87
Abstract. C27H4106N2C12, M.W. 560"5. Orthorhombic, P2x2121, a=7.76 (4), b= 52.6 (3), c=7.40 (4) A, U= 3021 A a, Z=4, Dx= 1-232 g cm -a. The final R value was 0-137 for 1249 reflexions. The packing of the hydrocarbon long chains is of the O± type and the chains make an angle of 45 ° with the basal plane (010).
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