101,945 research outputs found
FICZ and RA co-treatment inhibits cell proliferation and augments RA-induced G<sub>0</sub>/G<sub>1</sub> cell cycle arrest.
No full text<p>HL-60 cells were initiated in culture at 0.1 x 10<sup>6</sup> cells/ml with 1 μM RA, 100 nM FICZ, 1 μM α-NF and 1 μM β-NF as indicated. <b>(A).</b> Cells/ml as a function of time in culture. Cell densities in all the cultures remained similar for the first 48 h (averaging among the groups: 0.463±0.01 x 10<sup>6</sup> cells/ml). By 72 h, the cell population growth is inhibited the most by FICZ+RA (averaging 0.89 x 10<sup>6</sup> cells/ml), followed by β-NF+RA (averaging 1.05 x 10<sup>6</sup> cells/ml), compared to RA alone (averaging 1.23 x 10<sup>6</sup> cells/ml). For untreated cultures cell density was at 1.42 x 10<sup>6</sup> cells/ml on average. The cell density of FICZ treated cultures was 1.46 x 10<sup>6</sup> cells/ml on average. <b>(B).</b> Percent cells in G<sub>0</sub>/G<sub>1</sub> after 48 h in culture. After 48 h of culture, cell cycle arrest in G<sub>0</sub>/G<sub>1</sub> was augmented by FICZ+RA compared to RA alone (p = 0.0257). <b>(C)</b>. Percent cells in G<sub>0</sub>/G<sub>1</sub> after 72 h. in culture After 72 h of culture, FICZ+RA and β-NF+RA induce significantly more G<sub>0</sub>/G<sub>1</sub> arrest (P<0.0116 and p = 0.0263 respectively) compared to RA alone. AhR modulators used alone had no effect on the cell cycle.</p
Toxicity and cytochrome P450 1A mRNA induction by 6-formylindolo[3,2-b]carbazole (FICZ) in chicken and Japanese quail embryos
No full textThe tryptophan derivative formylindolo[3,2-b]carbazole (FICZ) binds with high ligand affinity to the aryl hydrocarbon receptor (AHR) and is readily degraded by AHR-regulated cytochrome P450 family 1 (CYP1) enzymes. Whether in vivo exposure to FICZ can result in toxic effects has not been examined and the main objective of this study was to determine if FICZ is embryotoxic in birds. We examined toxicity and CYP1 mRNA induction of FICZ in embryos from chicken (Gallus domesticus) and Japanese quail (Coturnix japonica) exposed to FICZ (2200 jag kg(-1)) by yolk and air sac injections. FICZ caused liver toxicity, embryo mortality, and CYP1A4 and CYP1A5 induction in both species with similar potency. This is in stark contrast to the very large difference in sensitivity of these species to halogenated AHR agonists. We also exposed chicken embryos to a low dose of FICZ (4 mu g kg(-1)) in combination with a CYP inhibitor, ketoconazole (KCZ). The mixture of FICZ and KCZ was lethal while FICZ alone had no effect at 4 mu g kg(-1). Furthermore, mixed exposure to FICZ and KCZ caused stronger and more long-lasting hepatic CYP1A4 induction than exposure to each compound alone. These findings indicate reduced biotransformation of FICZ by co-treatment with KCZ as a cause for the enhanced effects although additive AHR activation is also possible. To conclude, FICZ is toxic to bird embryos and it seems reasonable that the toxicity by FICZ involves AHR activation. However, the molecular targets and biological events leading to hepatic damage and mortality are unknown.</p
The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) binds multiple AHRs and induces multiple CYP1 genes via AHR2 in zebrafish
No full textThe tryptophan photooxidation product 6-formylindolo[3,2-b]carbazole (FICZ) has been proposed as a physiological ligand for the mammalian aryl hydrocarbon receptor (AHR), which it binds with high-affinity, inducing expression of cytochrome P450 1A1 (CYP1A1). We investigated whether the response to FICZ is evolutionarily conserved in vertebrates by measuring FICZ binding to two zebrafish AHRs (AHR1B and AHR2) and its ability to induce zebrafish CYP1 genes (CYP1A, CYP1B1, CYP1C1, CYP1C2, and CYP1D1) in vivo. Exposure of zebrafish embryos (48 h-post-fertilization; hpf) to 10 nM FICZ for 6 h caused strong induction of CYP1A mRNA and a statistically significant but modest induction of CYP1B1 and CYP1C1. Neither CYP1C2 nor CYP1D1 expression was induced by FICZ under the conditions of dose, time or developmental stage examined here. CYP1A induction was significantly greater after 6 h than after 12 h of exposure to FICZ, suggesting a rapid degradation of inducer. The 6-h EC50 values for induction of CYP1A and CYP1B1 by FICZ were 0.6 and 0.5 nM compared to 72-h EC50 values of 2.3 and 2.7 nM for PCB126, indicating that in zebrafish embryos FICZ is a more potent inducer than PCB126. FICZ at 10 nM was able to completely displace binding of 2,3,7,8-tetrachloro-1,6[3H]-dibenzo-p-dioxin to in vitro-expressed zebrafish AHR2 and AHR1B. Inhibition of AHR2 translation in zebrafish embryos by an AHR2-specific morpholino antisense oligonucleotide decreased the induction of CYP1A and CYP1B1 by FICZ and by PCB126. Together, these results demonstrate that FICZ is a potent AHR agonist in zebrafish, inducing expression of multiple CYP1 genes largely through AHR2. Evolutionary conservation of the response to FICZ is consistent with a possible role as an endogenous signaling molecule acting through the AHR
Evaluation of the clonogenic potential of day-4 FICZ-cultured CML CD34+ cells.
No full textA significant reduction of leukemic clonogenic potential was observed with a synergistic profile of FICZ with Imatinib (p = 0.0309, Panel A) and Dasatinib (p = 0.0292. (Panel B). Similarly, in three patients, LTC-IC assays started using 3-day FICZ-treated cells showed a significant growth inhibition of LTC-IC-derived clonogenic progenitors without synergistic profile with Imatinib. (Panel C). n = 3 experiments. CFC: Colony forming cells; IM: Imatinib; DASA: Dasatinib; DMSO: Dimethysulfoxide condition in which cells were cultured in the presence of DMSO at 0.01%.</p
Evaluation of the role of AHR agonist FICZ in the growth of leukemic CD34+ cells.
No full textCML CD34+ cells were cultured in the presence of indicated concentrations of FICZ and the cell numbers at day7 were compared to day 0. The use of FICZ induced a decrease of the growth of CD34+ cells at day+7 with the most inhibitory effects observed at concentrations of 100–200 nm (p = 0.0001, n = 3 experiments, ANOVA + Dunnett’s post-hoc test). Reported p-values are related to comparisons performed with the 0 nM dose. All p-values are adjusted for multiple comparisons.</p
Effects of UV and FICZ on the EGFR signalling in NHEK.
No full text<p><b>A</b>. Western blot detection of the phosphorylated forms of EGFR (P-EGFR) and ERK (P-ERK) in total lysates of untreated NHEK (-) and post-UV irradiation; <b>B</b>. Densitometry of the bands. *P<0.05 and <sup>§</sup>P<0.01 <i>versus</i> untreated controls (-). <b>C</b>. Western blots of nuclear non-phosphorylated (nEGFR) and phosphorylated EGFR (nP-EGFR) before and 20 min after exposure to UV. Histone 4 (H4) was used as a loading control; <b>D</b>. Densitometry of nEGFR and nP-EGFR bands. *P<0.05 <i>versus</i> untreated control (-). <b>E</b>. Western blot detection of the phosphorylated forms of EGFR (P-EGFR) and ERK (P-ERK) in total lysates of untreated NHEK (-) and after 30 min exposure to 0.1 or 1.0 µM FICZ. <b>F</b>. Densitometry of the bands. *P<0.05 <i>versus</i> untreated control (-). <b>G</b>. Western blots of nuclear non-phosphorylated (nEGFR) and phosphorylated EGFR (nP-EGFR) after 30 min exposure to 0.1 or 1.0 µM FICZ; <b>H</b>. Densitometry of nEGFR and nP-EGFR bands. *P<0.05 <i>versus</i> untreated controls.</p
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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3346: Samuel G. Freedman, author, 2013
No full textPhotograph of author Samuel G. Freedman, at NT Daily Slash meeting in the Mayborn School of Journalism at UNT
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