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41.
Liane Wehder Günther Ernst Anna C. Crecelius Orlando Guntinas-Lichius Christian Melle Ulrich S. Schubert Ferdinand von Eggeling 《The journal of histochemistry and cytochemistry》2010,58(10):929-937
Carcinoma tissue consists of not only tumor cells but also fibroblasts, endothelial cells or vascular structures, and inflammatory cells forming the supportive tumor stroma. Therefore, the spatial distribution of proteins that promote growth and proliferation in these complex functional units is of high interest. Matrix-assisted laser desorption/ionization imaging mass spectrometry is a newly developed technique that generates spatially resolved profiles of protein signals directly from thin tissue sections. Surface-enhanced laser desorption/ionization mass spectrometry (MS)combined with tissue microdissection allows analysis of defined parts of the tissue with a higher sensitivity and a broader mass range. Nevertheless, both MS-based techniques have a limited spatial resolution. IHC is a technique that allows a resolution down to the subcellular level. However, the detection and measurement of a specific protein expression level is possible only by semiquantitative methods. Moreover, prior knowledge about the identity of the proteins of interest is necessary. In this study, we combined all three techniques to gain highest spatial resolution, sensitivity, and quantitative information. We used frozen tissue from head and neck tumors and chose two exemplary proteins (HNP1–3 and S100A8) to highlight the advantages and disadvantages of each technique. It could be shown that the combination of these three techniques results in congruent but also synergetic data. (J Histochem Cytochem 58:929–937, 2010) 相似文献
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G. Möller 《Folia microbiologica》1985,30(3):203-211
The enzyme dextranase could degrade antigenic dextran in vivo even when given 6-15 d after the antigen. Dextranase injected after the antigen suppressed the immune response when given 24 but not 48 h after the antigen, indicating that the antigen must interact with the immune system for 48 h to initiate a response. Thereafter, the B cells are independent of further antigen stimulation. To show whether antibody-mediated suppression of the immune response was determinant specific FITC-conjugated SRC were applied as immunogen and antibodies were raised both against the carrier (SRC) and the FITC hapten. When these antibodies were injected 1-3 h after the immunogen they only suppressed the immune response to the corresponding determinant. Anti-carrier antibodies usually enhanced the response to the hapten. Therefore, antibody-mediated suppression of the immune response is determinant-specific and cannot be mediated in vivo to a detectable extent by the Fc part of the antibodies. 相似文献
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Summary 1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve-diaphragm disclosed that the inhibitory effect of HgCl2, 3.7 × 10–5
M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10 min. This activity-dependent enhancement suggested an inhibitory mechanism of HgCl2 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2+)0 or (Ca2+)i, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)i.2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca2+ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgCl2-induced inhibition.3. Since caffeine depletes the intracellular Ca2+ stores of the smooth endoplasmic reticulum, HgCl2 probably inhibits by binding to SH groups of transport proteins conveying the messenger function of (Ca2+)i. In the muscle cell this leads to inhibition of contraction. In the nerve terminal, an additional enhancement of the HgCl2-induced inhibition, by inhibiting reuptake of choline by TEA and tetanic stimulation, suggested that HgCl2 inhibited a (Ca2+)i signal necessary for this limiting factor in resynthesis of acetylcholine.4. The (Ca2+)0 signal necessary for stimulus-induced release of acetylcholine was not affected by HgCl2. Hyperpolarization in K+-free solution antagonized the inhibitory effect of HgCl2 at indirect stimulation, and Ca2+-free solution enhanced the inhibitory effect at direct stimulation. K+ depolarization, membrane electric field increase with high Ca2+, membrane stabilization with lidocaine, and half-threshold stimulation, did not change the inhibitory effect of HgCl CH3HgCl, 1.85 × 10–5
M, disclosed a synergistic interaction with caffeine during direct, but not during indirect, stimulation. 相似文献
47.
Michael H Woo John R Vance Ana R Otero Marcos Christian Bailly Mary-Ann Bjornsti 《The Journal of biological chemistry》2002,277(6):3813-3822
DNA topoisomerase I (Top1p) catalyzes topological changes in DNA and is the cellular target of the antitumor agent camptothecin (CPT). Non-CPT drugs that target Top1p, such as indolocarbazoles, are under clinical development. However, whether the cytotoxicity of indolocarbazoles derives from Top1p poisoning remains unclear. To further investigate indolocarbazole mechanism, rebeccamycin R-3 activity was examined in vitro and in yeast. Using a series of Top1p mutants, where substitution of residues around the active site tyrosine has well-defined effects on enzyme catalysis, we show that catalytically active, CPT-resistant enzymes remain sensitive to R-3. This indolocarbazole did not inhibit yeast Top1p activity, yet was effective in stabilizing Top1p-DNA complexes. Similar results were obtained with human Top1p, when Ser or His were substituted for Asn-722. The mutations altered enzyme function and sensitivity to CPT, yet R-3 poisoning of Top1p was unaffected. Moreover, top1delta, rad52delta yeast cells expressing human Top1p, but not catalytically inactive Top1Y723Fp, were sensitive to R-3. These data support hTop1p as the cellular target of R-3 and indicate that distinct drug-enzyme interactions at the active site are required for efficient poisoning by R-3 or CPT. Furthermore, resistance to one poison may potentiate cell sensitivity to structurally distinct compounds that also target Top1p. 相似文献
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Kasper Stovgaard Christian Andreetta Jesper Ferkinghoff-Borg Thomas Hamelryck 《BMC bioinformatics》2010,11(1):429