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  • 1
    Digitale Medien
    Digitale Medien
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Immunology 23 (2005), S. 387-414 
    ISSN: 0732-0582
    Quelle: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Thema: Biologie , Medizin
    Notizen: The newly discovered CATERPILLER (CLR) gene family encodes proteins with a variable but limited number of N-terminal domains, followed by a nucleotide-binding domain (NBD) and leucine-rich repeats (LRR). The N-terminal domain consists of transactivation, CARD, Pyrin, or BIR domains, with a minority containing undefined domains. These proteins are remarkably similar in structure to the TIR-NBD-LRR and CC-NBD-LRR disease resistance (R) proteins that mediate immune responses in plants. The NBD-LRR architecture is conserved in plants and vertebrates, but only remnants are found in worms and flies. The CLRs regulate inflammatory and apoptotic responses, and some act as sensors that detect pathogen products. Several CLR genes have been genetically linked to susceptibility to immunologic disorders. We describe prominent family members, including CIITA, CARD4/NOD1, NOD2/CARD15, CIAS1, CARD7/NALP1, and NAIP, in more detail. We also discuss implied roles of these proteins in diversifying immune detection and in providing a check-and-balance during inflammation.
    Materialart: Digitale Medien
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Cancer immunology immunotherapy 49 (2000), S. 78-84 
    ISSN: 1432-0851
    Schlagwort(e): Key words Lung ; Chemokines ; Signal transduction ; Transcription factors
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Lung cancer is a leading cause of cancer-related death in the United States. For this reason we chose to study the specific cellular effects that one chemotherapeutic agent, paclitaxel, has on lung carcinoma. In addition to its known mechanism of action, which is to stabilize microtubules, paclitaxel has been shown to have other interesting and relevant cellular effects. In this report, we demonstrate that a subset of human lung carcinoma cell lines respond to paclitaxel treatment with an up to a fivefold increase in the production of interleukin-8 (IL-8). We demonstrate that this increased production is specific to IL-8 but not to other chemokines, and is both dose- and time-dependent. Increased IL-8 mRNA is seen as early as 45 min with a peak at 4 h after paclitaxel treatment. This increase in mRNA is due to transcriptional activation because actinomycin D treatment blocked the increase. Paclitaxel also activates the mitogen-activated protein kinase family member, JNK1, in dose-dependent fashion. IL-8 enhancement is completely abolished with the use of an inhibitor of NF-κB, the super-repressor IκB. Similar results were obtained upon the inhibition of AP-1 activation with the MEK1/2 inhibitor, U0126. By gaining a better understanding of the differences in cellular response to paclitaxel chemotherapy, these findings might lead to either improved patient selection or to the development of adjuvant therapy targeted at specific-cell signaling proteins.
    Materialart: Digitale Medien
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  • 3
    ISSN: 1432-0851
    Schlagwort(e): Key words Human ; Monocytes/macrophages ; T lymphocytes ; Cytokines ; Chemokines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Paclitaxel or Taxol has attracted a great deal of attention in recent years because of its immense success as a chemotherapeutic agent for numerous types of cancer. It is known that paclitaxel stabilizes microtubules, and this characteristic is the presumed primary mechanism for its antitumor activity. Recently, however, paclitaxel’s ability to regulate gene expression, particularly in the murine system, has been reported by several groups. Here, we present research examining paclitaxel’s ability to alter expression of the interleukin-1β (IL-1β) and IL-8 cytokines in primary human monocytes, T lymphocytes, and four human breast cancer cell lines: MCF-7, ZR-75-1, MDA-MB-468, and MDA-MB-231. This report shows for the first time that treatment with 5–50 μM paclitaxel increases steady-state levels of IL-1β mRNA in unprimed human monocytes, MCF-7, and ZR-75-1 cells. Monocytes from eight donors in 16 experiments showed increased IL-1β secretion upon treatment; however, the increase in IL-1β production by monocytes was predicated on culturing in the absence of fetal bovine serum or in the presence of autologous human serum. In contrast to the IL-1β results, paclitaxel did not have significant effects on IL-8 expression by monocytes, T lymphocytes, or the breast cancer cells. These data show a specific effect of paclitaxel on cytokine synthesis by both immune cells and cancer cells.
    Materialart: Digitale Medien
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    Somatic cell and molecular genetics 10 (1984), S. 217-224 
    ISSN: 1572-9931
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Expression of class I histocompatibility antigens (HLA-A and B) on hybrids of human T and B lymphoblastoid cell lines (LCL) was examined. The T-LCL CEM expressed low levels of HLA-A and B antigens. CEMR and CEMR.3, two 8-azaguanine- and ouabainresistant sublines of CEM used for fusion, expressed no detectable HLA-B antigens and expressed HLA-A antigens at a level below that of CEM. The three B-LCL studied expressed class I histocompatibility antigens at levels 50-to 80-fold in excess of that found on CEM as assessed by indirect immunofluorescence and flow cytometry. Total levels of class I histocompatibility antigens on hybrids of CEMR and CEMR.3 with B-LCL were similar to those found on the B-LCL. CEM-encoded HLA-A and B antigens were expressed on the hybrids at levels much greater than those seen on CEM itself; expression by the hybrids of CEM-encoded and B-LCL-encoded class I antigens was comparable. By RNA-DNA filter hybridization, CEMR.3 was found to have extremely low levels of class I heavy-chain mRNA compared with two B-LCL and with HSB, a T-LCL that expresses high levels of class I histocompatibility antigens. Thus, the paucity of HLA-A and B expression by CEMR.3 (and by inference, CEMR and CEM), as well as the enhancement of CEM-encoded HLA-A and B antigen expression on B-LCL × T-LCL hybrids, must be due, at least in part, to modulation of the level of transcripts encoding HLA class I heavy chains.
    Materialart: Digitale Medien
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 17 (1983), S. 295-301 
    ISSN: 1432-1211
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract Our results, using radiation-induced bone marrow chimeras, demonstrate that the la antigen found in the brains of such animals is produced by cells having precursors in the bone marrow. These cells are not immediately blood borne since no IgM is detected in these brains. This rules out the obvious possibility of B-lymphocyte contamination as the source of la in the brain cell preparations. It thus appears that the central nervous system, like many other nonlymphoid organs, has a source of Ia-positive cells that are derived from bone marrow precursors.
    Materialart: Digitale Medien
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  • 6
    ISSN: 1432-1211
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Abstract We examined the possibility that one mechanism for controlling HLA-DR α gene expression occurs through DNA hypomethylation. We employed the restriction enzyme Hpa II, which recognizes the sequence 5′CCGG3′ but not 5′CmCGG3′, to study DNA methylation. We first compared a DR-positive B lymphoblastoid cell line (LCL) with an isogenic DR-negative T-LCL. Using a genomic probe for the DR α gene, we showed that an Hpa II digestion of DNA from the B-LCL resulted in bands of lower molecular weight than that of the T-LCL. This indicates that the B-LCL DR gene is hypomethylated relative to the T-LCL gene. Demethylation of the gene from the B-LCL is incomplete, suggesting that complete demethylation is not required for its expression. We also examined somatic cell hybrids of T-LCL and B-LCL since the DR α gene, which is inactive in the T-LCL, is expressed in the hybrids, providing a system to study DR α gene induction. We examined the hybrid line 174 × CEM.T1, which contains and expresses solely the DR α gene from the T-LCL parent since both copies of the DR α gene from the B-LCL parent, 174, are deleted. The expressed DR α gene from the hybrid was compared with the unexpressed gene from the T-LCL parental line, and again an association between DR α gene expression and DNA hypomethylation was observed. In contrast to the DR α gene from B-LCL, which is not completely demethylated, the DR α gene in this hybrid line is not methylated at either of the Msp I sites covered by our probe. This suggests that different regulatory mechanisms operating through DNA methylation may be involved in the expression of DR α genes from T-LCL and B-LCL. Examination of another hybrid line which has DR α genes from both parental lines supports this contention. The implications of these findings are discussed.
    Materialart: Digitale Medien
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    Immunogenetics 35 (1992), S. 136-139 
    ISSN: 1432-1211
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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