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991.
Growth-related expression of a double-stranded RNA-dependent protein kinase in 3T3 cells 总被引:14,自引:0,他引:14
Cultured mouse 3T3-F442A and 3T3-C2 fibroblasts exhibit a transient double-stranded RNA (dsRNA)-dependent phosphorylation of a 67,000-dalton protein (67K) without prior treatment with interferon (IFN). This phosphoprotein is similar but not identical to the dsRNA-dependent eukaryotic initiation factor-2 (eIF-2) alpha protein kinase (dsI), which regulates protein synthesis in rabbit reticulocytes. We have studied the relationship between cell growth and phosphorylation of the 67K protein (designated 3T3-dsRNA-dependent eIF-2 alpha kinase). A low level of dsRNA-dependent phosphorylation of 3T3-dsI was detectable in extracts prepared from cells not treated with IFN and grown at a low cell density. The phosphorylation of dsI and the phosphorylation of a 38K protein identified as the alpha-subunit (38K) of 3T3-eIF-2 (eIF-2 alpha) occurred concomitantly; the levels of these phosphorylations confluent and thereafter decreased markedly. Treatment of cells with IFN at all stages of growth resulted in an increase in phosphorylation of dsI. 3T3-F442A and 3T3-C2 fibroblasts were found to produce and secrete IFN at levels sufficient to induce an elevated dsI activity. 相似文献
992.
Toxin gamma is a basic, low-molecular-weight, neurotoxic protein, isolated from the venom of the Brazilian scorpion, Tityus serrulatus. Raman spectra (400-1800 cm-1 region) of this toxin in both the lyophilized state and in 0.1 M acetate buffer (pH 4.5) and the infrared spectrum (700-4000 cm-1 region) of a solid film were investigated. From the vibrational spectra, it can be concluded that the polypeptide backbone of toxin gamma consists of a mixture of the different secondary structures, with predominance of beta-sheet, followed by unordered structure and alpha-helix, with some evidence of beta-turn structures. The four disulfide bridges assume the gauche-gauche-gauche conformation of the CCSSCC fragments. The intensity ratio of the doublet at 853 and 828 cm-1 suggests that four out of the five tyrosine residues are exposed. The three tryptophan residues are exposed on the surface, and the single methionine residue assume the gauche-gauche conformation. Toxin gamma retains full activity in the pH 4.5-7.5 range, but is almost completely inactivated at pH 11.5. 相似文献
993.
Transfer of N, N'-diacetylchitobiose from dolichyl diphosphate into a gray matter membrane glycoprotein 总被引:1,自引:0,他引:1
Gray matter and white matter membranes catalyze the transfer of label from UDP-N-acetyl-[] glucosamine into N-acetyl[]glucosaminyl-pyrophosphoryl-dolichol, N,N′-diacetyl []chitobiosyl-pyrophosphoryl-dolichol, and N-acetyl[]glucosamine-labeled glycoprotein. Gel filtration of the Pronase digests of gray matter N-acetyl[]glucosamine-labeled glycoprotein reveals two N-acetyl[]glucosamine-labeled glycopeptide fractions. One fraction (A) contains approximately eight glycose units. All of the radioactivity is at nonreducing termini and can be released by treatment with an exo-β-N-acetylglucosaminidase. A smaller N-acetyl[]glucosamine-labeled glycopeptide (B) is recovered in the elution volume expected for an asparaginyl disaccharide. Structural studies show that the labeled saccharide unit in glycopeptide B is N,N′-diacetyl[]chitobiose. The linkage between the -labeled disaccharide and the polypeptide has the properties of an N-glycosidic attachment to asparagine. Only the larger N-acetyl[]glucosamine-labeled glycopeptide (A) is found in Pronase digests of white matter membrane N-acetyl[]glucosamine-labeled glycoprotein after incubation with UDP-N-acetyl[]glucosamine. When gray matter membranes are incubated with UDP-N-acetyl[]glucosamine in the presence of tunicamycin or UMP, the labeling of glycolipid and the asparaginyl disaccharide is inhibited. UMP and tunicamycin have no effect on the transfer of N-acetyl[]glucosamine to external acceptor sites of the larger glycopeptide (A). The transfer of N,N′-diacetyl[]-chitobiose from carrier lipid to protein is observed when extensively washed membranes containing endogenous, prelabeled -labeled glycolipids are incubated in the presence or absence of unlabeled GDP-mannose. UMP treatment of the prelabeled membranes selectively discharged over 80% of the label from N-acetyl[]glucosaminyl-pyrophosphoryl-dolichol, but had no effect on the transfer of the -labeled disaccharide to protein. All of these results are concordant with transfer of N,N′-diacetylchitobiose from dolichyl diphosphate to gray matter glycoprotein. The major membrane glycoprotein labeled by the lipid-mediated []disaccharide transfer reaction has an apparent molecular weight of 24,000. Tunicamycin prevents the enzymatic labeling of the gray matter glycoprotein having an apparent molecular weight of 24,000. 相似文献
994.
TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA),
particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness
of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question
the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide
only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the
economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable. 相似文献
995.
Background
DNA Microarrays have become the standard method for large scale analyses of gene expression and epigenomics. The increasing complexity and inherent noisiness of the generated data makes visual data exploration ever more important. Fast deployment of new methods as well as a combination of predefined, easy to apply methods with programmer's access to the data are important requirements for any analysis framework. Mayday is an open source platform with emphasis on visual data exploration and analysis. Many built-in methods for clustering, machine learning and classification are provided for dissecting complex datasets. Plugins can easily be written to extend Mayday's functionality in a large number of ways. As Java program, Mayday is platform-independent and can be used as Java WebStart application without any installation. Mayday can import data from several file formats, database connectivity is included for efficient data organization. Numerous interactive visualization tools, including box plots, profile plots, principal component plots and a heatmap are available, can be enhanced with metadata and exported as publication quality vector files. 相似文献996.
997.
A 46-year-old man with pentazocine-induced agranulocytosis is described. In previously reported cases of a complete absence of mature neutrophils in the peripheral blood and bone marrow the patients had undergone marrow-depressing treatment with radiation and antineoplastic drugs. This case is unique in that the patient had complete agranulocytosis without predisposing factors. 相似文献
998.
T-cell responsiveness in Mycobacterium lepraemurium infections in a "resistant" (CBA) and a "susceptible" (BALB/c) mouse strain 总被引:5,自引:0,他引:5
S J Brett 《Cellular immunology》1984,89(1):132-143
Antigen-specific and mitogen-nonspecific T-lymphocyte proliferation and lymphokine release (interleukin 2 and macrophage activation factor) were studied in BALB/c and CBA mice infected intravenously with 10(8) Mycobacterium lepraemurium organisms. The responsiveness of spleen cells from infected animals to Con A and specific MLM antigen declined as the infection progressed. Thus, the decreased responsiveness appeared earlier and was more profound in the relatively susceptible BALB/c strain than in the relatively resistant CBA strain. Nylon-wool-purified, T-cell-enriched spleen cells from both strains, however, responded to both M. lepraemurium antigen and Con A until the later stages of infection (17 weeks postinfection). The relevance of nonspecific immunodepression mediated by nylon-wool-adherent spleen cells to the progressive nature of this infection is discussed. 相似文献
999.
The antigenic structure of human albumin was investigated in order to establish whether or not there was any similarity between its antigenic sites. Using immunoadsorbent columns prepared with cyanogen bromide fragments of human serum albumin, antibodies directed against different portions of the albumin molecules were isolated. Measurement of the amount of the antibodies isolated and study of their specificity by inhibition techniques show that these subpopulations of antibodies reacted not only with the fragment used for their isolation (homologous) but also with the other fragments (heterologous). Heterologous fragments were inhibiting only at a very high concentration with regard to the homologous ones. These results show that there is a weak cross-reactivity between different portions of the albumin molecule. This reaction is most probably due to the homology existing in the sequence of the human albumin molecule which has arisen by gene duplication. The same type of behavior can be predicted to extent to other molecules which have evolved by similar mechanisms. 相似文献
1000.
Anti-idiotypic monoclonal antibodies have been prepared that represent the internal image of nicotine and are specific for the nicotine binding site on rat brain receptor. Specificity of these antibodies for the combining site on anti-nicotine was demonstrated by their ability to inhibit binding of monoclonal anti-nicotine to immobilized nicotine-polylysine. Furthermore, purified rat brain nicotine receptor but not acetylcholine receptor from fish electric organ effectively competed with anti-nicotine for immobilized nicotine and for immobilized anti-idiotype. Only 9 pmoles of naturally occurring (-)-nicotine inhibited idiotype-anti-idiotype binding by 50% whereas 11 times more (+)-nicotine was required. Acetylcholine, several cholinergic agonists and antagonists, nicotine metabolites, and other structurally related compounds were poor inhibitors. 相似文献