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11.
Effect of tumor necrosis factor-α and interferon-γ on the growth of a human salivary gland cell line
Ava J. Wu Regina H. Kurrasch Joseph Katz Philip C. Fox Bruce J. Baum Jane C. Atkinson 《Journal of cellular physiology》1994,161(2):217-226
Interferon-γ (IFN-γ) is a product of activated T-lymphocytes, and tumor necrosis factor-α (TNF-α) is a product of both lymphocytes and macrophages. These cell types are often present at sites of tissue damage secondary to chronic infection or autoimmune disease. The purpose of this study was to characterize the effects of TNF-α and IFN-γ on a human submandibular gland epithelial cell line (HSG). IFN-γ caused a concentration-dependent decrease in HSG cell growth (~70% in 6 days). Conversely, TNF-α alone had little effect on the growth of these cells. When these cytokines were added in combination (20 units/ml TNF-α and 1,000 units/ml of IFN-γ), there was a synergistic antiproliferative effect; no apparent cell growth was observed. The cytokine-induced antiproliferative effect was reversible. After the apparent cessation of cell growth for 3–6 days, removal of the cytokines permitted complete growth recovery. Further, cells that recovered and exhibited growth patterns that were similar to control cells remained susceptible to the antiproliferative effects of the cytokines. Flow cytometry revealed that the percentage of cells in G0/G1 with the combination of cytokines was significantly increased by 24 h. The antiproliferative effect of IFN-γ alone and that of IFN-γ and TNF-α in combination were blocked completely using an antibody to the IFN-γ receptor. A hypothesized mechanism of tissue damage in autoimmune inflammatory disorders is via up-regulation of cell surface markers such as intercellular adhesion molecule type I (ICAM-1) and histocompatibility antigen HLA-DR which can exacerbate the inflammatory process. Treatment of HSG cells with IFN-γ, with or without TNF-α, resulted in increased levels of ICAM-1 and the acquisition of HLA-DR expression. These aggregate data suggest that IFN-γ alone can regulate the expression of cell surface markers involved in the inflammatory process as well as cause a potent yet reversible inhibition of HSG cell growth that is modulated by the presence of TNF-α. © 1994 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
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14.
D. J. Easton 《CMAJ》1984,130(4):418-20,422
Severe thrombocytopenia associated with acute folic acid deficiency in two inpatients is described. Both patients had severe hemorrhagic manifestations. A similar syndrome has previously been described in patients who have undergone extensive surgery or dialysis or both. The present cases show that acute folic acid deficiency can occur in other circumstances and may go unrecognized because other signs in the peripheral blood of a megaloblastic process may be minimal. A good response was obtained with folic acid therapy. 相似文献
15.
D M Easton 《Journal of theoretical biology》1979,76(3):335-349
From the assumption that the fractional increase of HbO2 as a function of pO2 is proportional to HbO2, and that the proportionality coefficient of that relation decreases exponentially with pO2, an equation can be derived that gives an excellent fit to the full range of the oxyhemoglobin dissociation curve. To generate this asymmetric sigmoid curve, only one rate constant is required. In addition, the initial and final conditions specify an intermediate constant B, the “shift factor” that determines the horizontal displacement of the curve. The rate constant K specifies the rate of change of the specific rate of increase of HbO2 with respect to O2. Governing the slope of the curve, K decreases as temperature and acidity increase, while the B factor remains constant. For Hb in solution, B decreases with decrease of concentration, but K appears to be unchanged. The expo-exponential constants provide convenient specification of the full course and position of the oxyhemoglobin dissociation curve. 相似文献
16.
E W Easton J G Bolscher D H van den Eijnden 《The Journal of biological chemistry》1991,266(32):21674-21680
Expression of ras oncogenes in NIH 3T3 fibroblasts results in the acquisition by these cells of an invasive potential concomitant with the appearance of cell surface asparagine-linked complex-type glycan structures of a higher average molecular weight (Bolscher, J.G. M., van der Bijl, M. M. W., Neefjes, J. J., Hall, A., Smets, L.A., and Ploegh, H.L. (1988) EMBO J. 7, 3361-3368). We have investigated the enzymatic basis for the altered glycosylation by assessing the activities of all major Golgi glycosyltransferases involved in the synthesis of these structures. Use was made of a stable transfectant cell line (T15) containing the N-ras-protooncogene under the control of a glucocorticoid-inducible mouse mammary tumor virus promoter. Upon induction of the ras gene with dexamethasone: 1) the levels of N-acetylglucosaminyltransferase I and II were essentially unaltered, indicating an unaffected potential to synthesize complex-type glycans; 2) the activities of the branching N-acetylglucosaminyltransferase III and V were elevated 2- to 2.5-fold suggesting the formation of increased amounts of bisected glycans and of structures carrying a Gal beta 1----GlcNAc beta 1----6Man-branch; 3) the levels of the elongating beta 4-galactosyltransferase and beta 3-N-acetylglucosaminyl-transferase were increased 5- to 7-fold indicating a strongly enhanced capacity to synthesize polylactosaminoglycan chains; 4) the level of the major chain-terminating enzyme, alpha 3-galactosyltransferase, was slightly decreased (0.7-fold), whereas those of the alpha 3- and alpha 6-sialyltransferases were slightly elevated (1.3- and 2-fold, respectively), suggesting a shift from termination by alpha-galactosyl residues to termination by sialic acid moieties. Studies on the acceptor specificities of the different glycosyltransferases indicate that these changes occur in a coordinated manner in which the effects of altered glycosyltransferase expression levels amplify each other. Analysis of the size of cell surface complex-type glycopeptides before and after digestion with neuraminidase and endo-beta-galactosidase suggested an increased sialic acid density, an increase in the number and/or length of polylactosaminoglycan chains, and an increased branching of the glycans upon N-ras induction. The enzymatic results explain these structural changes and allow us to define the alterations in glycosylation pathways associated with ras expression. 相似文献
17.
The thermal incorporation and channel formation of gramicidins A and B into phosphatidylcholine/phosphatidylglycerol large unilamellar vesicle membranes was studied using 23Na NMR. Delta H and delta S of activation for channel formation for gramicidin A are 11.8 kcal/mol and -11 e.u., respectively. For gramicidin B, delta H and delta S of activation are 14.6 kcal/mol and -4 e.u., respectively. Possible reasons for the differences in delta H and delta S of activation between the two analogues are discussed. 相似文献
18.
The complete amino acid sequence of human fibroblast interferon as deduced using synthetic oligodeoxyribonucleotide primers of reverse transcriptase 总被引:6,自引:4,他引:2 下载免费PDF全文
19.
ATCC4117 is a strain of S. cerevisiae that undergoes a single nuclear division during sporulation to produce asci containing two diploid ascospores (Grewal and Miller 1972). All clones derived from these spores are sporulation-capable and, like the parental strain, form two-spored asci. In this paper, we describe the genetic analysis of ATCC4117. In tetraploid hybrids of vegetative cells of the ATCC4117 diploid and a/a or α/α diploids, the production of two-spored asci is recessive. From these tetraploids, we have isolated two recessive alleles, designated spo12–1 and spo13–1, each of which alone results in the production of asci with two diploid or near-diploid spores. These alleles are unlinked and segregate as single nuclear genes. spo12–1 is approximately 22 cM from its centromere; spo13–1 has been localized to within 1 cM of arg4 on chromosome VIII. This analysis also revealed that ATCC4117 carries a diploidization gene allelic to or closely linked to HO, modifiers that reduce the number of haploid spores per ascus and alleles affecting the total level of sporulation. 相似文献
20.
Grammatopoulos DK Dai Y Randeva HS Levine MA Karteris E Easton AJ Hillhouse EW 《Molecular endocrinology (Baltimore, Md.)》1999,13(12):2189-2202
CRH exerts its actions via activation of specific G protein-coupled receptors, which exist in two types, CRH-R1 and CRH-R2, and arise from different genes with multiple spliced variants. RT-PCR amplification of CRH receptor sequences from human myometrium and fetal membranes yielded cDNAs that encode a novel CRH-R type 1 spliced variant. This variant (CRH-R1d) is present in the human pregnant myometrium at term only, which suggests a physiologically important role at the end of human pregnancy and labor. The amino acid sequence of CRH-R1d is identical to the CRH-R1alpha receptor except that it contains an exon deletion resulting in the absence of 14 amino acids in the predicted seventh transmembrane domain. Binding studies in HEK-293 cells stably expressing the CRH-R1d or CRH-R1alpha receptors revealed that the deletion does not change the binding characteristics of the variant receptor. In contrast, studies on the G protein activation demonstrated that CRH-R1d is not well coupled to the four subtypes of G proteins (G(s), G(i), G(o), G(q)) that CRH-R1alpha can activate. These data suggest that although the deleted segment is not important for CRH binding, it plays a crucial role in CRH receptor signal transduction. Second messenger studies of the variant receptor showed that CRH and CRH-like peptides can stimulate the adenylate cyclase system, with reduced sensitivity and potency by 10-fold compared with the CRH-R1alpha. Furthermore, CRH failed to stimulate inositol trisphosphate production. Coexpression studies between the CRH-R1d or CRH-R1alpha showed that this receptor does not play a role as a dominant negative receptor for CRH. 相似文献