1,722,894 research outputs found
Crystallographic structure of the K-7174/proteasome complex.
No full text<p>A. An overall ribbon diagram showing the folds of ß1 to ß7 subunits in the proteasome. The ß4 and ß5 subunits are colored yellow and blue, respectively. The K-7174 molecules bound to each ß subunit are shown as a space-filling representation colored green. Red spots indicate oxygen atoms. B. The final averaged electron density map (2<i>F</i>o-<i>F</i>c) covering K-7174 is shown (contoured at 1∂) (upper panel). A schematic diagram showing the interactions between K-7174 and the ß4 and ß5 subunits. The residues of ß4 and ß5 subunits associated with K-7174 are colored yellow and blue, respectively. A hydrogen bond is shown as a green dotted line (lower panel). C. A schematic diagram showing the interactions between K-7174 and the ß1 and ß2 subunits. The residues of ß1 and ß2 subunits associated with K-7174 are shown. A hydrogen bond is shown as a green dotted line.</p
A straightforward synthesis of K-7174, a GATA-specific inhibitor
No full textK-7174, a GATA-specific inhibitor, is a putative anti-inflammatory agent that attenuates effects of inflammatory cytokines in certain cell types. An expeditious four-step synthesis of K-7174 is described in this paper. The route employs Wittig olefination and bis-alkylation of homopiperazine as the key reactions. The iodinecatalyzed isomerization of the Z-isomer results in complete conversion to the E-isomer is the highlight of our synthetic endeavors
Inhibition of 20S proteasome activity by K-7174.
No full text<p>A. We treated purified erythrocyte-derived 20 S proteasome with either K-7174 or bortezomib at the indicated doses and determined chymotrypsin-like, caspase-like and trypsin-like activities as described in the legend of Fig. 1. B. RPMI8226 cells were treated with either K-7174 or bortezomib at the indicated doses, and analyzed for proteolytic activities. C. MM cell lines (KMS12-BM, U266, and RPMI8226) were cultured with K-7174 or bortezomib (Bort) at the indicated doses for 48 hours. Whole cell lysates were subjected to immunoblotting for ubiquitinated proteins and GAPDH (internal control). D. MM cell lines were cultured with either K-7174 (5 µM for U266 and 10 µM for KMS12-BM and RPMI8226) or the vehicle alone (Control) for up to 3 days. Whole cell lysates were prepared at given time points and subjected to immunoblotting as described above. E. MM cell lines were cultured in the absence (None) or presence of K-7174 or bortezomib (Bort) at the indicated doses for 48 hours, and subjected to immunoblotting for lysine48-linked polyubiquitinated proteins (K48-Ubiq), ubiquityl histone H2A (Ubiq-H2A), and GAPDH (internal control).</p
K-7174 and bortezomib exert additive cytotoxicity against MM cell.
No full text<p>A. We treated RPMI8226 cells with K-7174 (10 µM), bortezomib (5 nM) or both agents, and determined chymotrypsin-like, caspase-like and trypsin-like activities. Results are represented as relative fluorescence units (RFU) with vehicle controls set at 100%. The means ± S.D. (bars) of three independent experiments are shown. Asterisks indicate p<0.01 by paired Student’s <i>t</i>-test. B. We cultured KMS12-BM, U266 and RPMI8226 cells in the absence or presence of K-7174, bortezomib or both agents for 48 hours at the indicated doses. Whole cell lysates were subjected to immunoblotting for ubiquitinated proteins and GAPDH (internal control). Data are representative of multiple independent experiments. C. Isobolograms of simultaneous exposure of three MM cell lines to K-7174 and bortezomib. The concentrations that produced 80% growth inhibition are expressed as 1.0 on the ordinate and abscissa of isobolograms. The envelope of additivity, surrounded by solid and broken lines, was constructed from dose–response curves of bortezomib and K-7174. The combination is regarded as additive, because all data points fall within the envelope of additivity. The isobolograms shown are representative of at least three independent experiments. Each point represents the mean of at least three independent experiments; standard deviations were less than 25% and were omitted.</p
The antimicrobial activity of the cephalosporin CGP 7174/E against Pseudomonas aeruginosa in comparison to carbenicillin, piperacillin and cefotaxime
No full textA comparative study on the minimal inhibitory concentrations (MIC) of CGP 7174/E, piperacillin, cefotaxime and carbenicillin used against 100 strains of Pseudomonas aeruginosa showed the following data: CGP 7174/E: 1.56 mcg/ml; piperacillin: 3.12 mcg/ml; cefotaxime: 12.5 mcg/ml; carbenicillin: 25 mcg/ml (mean MIC values suggest that CGP 7174/E is the most active). Eleven percent of the Pseudomonas aeruginosa strains were resistant to carbenicillin (MIC > 100 mcg/ml). The minimal inhibitory concentrations of the 3 tested antibiotics (piperacillin, cefotaxime and CGP 7174/E) are 2- to 4-fold higher for these carbenicillin-resistant strains.SCOPUS: NotDefined.jinfo:eu-repo/semantics/publishe
Suppression of cytokine response by GATA inhibitor K-7174 via unfolded protein response
No full textK-7174, a GATA-specific inhibitor, is a putative anti-inflammatory agent that attenuates effects of inflammatory cytokines in certain cell types. However, molecular mechanisms involved have not been elucidated. We found that, in glomerular podocytes, induction of monocyte chemoattractant protein 1 (MCP-1) and inducible nitric oxide synthase (iNOS) by TNF- was abrogated by K-7174. It was correlated with unexpected induction of unfolded protein response (UPR) evidenced by: (1) induction of endogenous indicators 78 kDa glucose-regulated protein and CCAAT/enhancer-binding protein–homologous protein, and (2) suppression of an exogenous indicator, endoplasmic reticulum stress-repressive alkaline phosphatase. In podocytes, induction of UPR by either tunicamycin, thapsigargin, A23187 or AB5 subtilase cytotoxin completely reproduced the suppressive effect of K-7174. Furthermore, K-7174-elicited UPR abrogated induction of MCP-1 and iNOS not only by TNF- but also by medium conditioned by activated macrophages. These results suggested a novel, UPR-dependent mechanism underlying the anti-inflammatory potential of K-7174.http://www.elsevier.com/wps/find/journaldescription.cws_home/622790/description#descriptio
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Comparison of K-7174 and bortezomib in cytotoxic activity and proteasome binding.
No full text<p>A. Cell proliferation was measured by MTT assays after culturing with serially diluted K-7174, K-10487 and bortezomib for 72 hours. Absorbance at 450 nm was analyzed with a microplate reader, and expressed as a percentage of the value of corresponding untreated cells. The IC<sub>50</sub> value was defined as the concentration of each drug that produces 50% inhibition of cell growth. The means ± S.D. (bars) of three independent experiments are shown. Asterisks indicate “not determined”. B. Overall crystallographic structures showing the folds of ß1 to ß7 subunits in the proteasome bound with K-7174 (left panel) and bortezomib (right panel). Mutation sites observed in bortezomib-resistant cells are circled. C. Structure of the proteasome in complex with bortezomib (PDB cord 2F16) overlapped that with K-7174 described here. Only the protein atoms of the bortezomib-bound form are shown. Bortezomib-resistant mutant residues (Ala49, Thr21, Cys52 and Met45) are colored red and shown as a space-filling diagram.</p
Take on TB : 7174 TB cases reported in the U.S. in 2020 [Spanish]
No full textTake on TB : 7174 TB cases reported in the U.S. in 2020 [Spanish]Demasiadas personas en los EE. UU. todav\ueda presentan tuberculosis (TB)Para informarse m\ue1s sobre la TB, visite www.cdc.gov/tb/esp326944A MLS327590TB_US_Surveill_InfoGrPoster_Spanish_FullPg.pdf20211097
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