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Kenneth J. Ryan Gerald M. Needham Carol L. Dunsmoor John C. Sherris 《Applied microbiology》1970,20(3):447-451
The stability of chemotherapeutic agents incorporated into agar plates was studied by comparison of minimum inhibitory concentrations on fresh and stored plates and by direct bioassay of the chemotherapeutic agar plates. Plates were stored in sealed bags at 4 C. No loss of bioactivity was demonstrated after 30 days of storage in plates containing methicillin, erythromycin, cephalothin, tetracycline, chloramphenicol, kanamycin, streptomycin, polymyxin B, or nalidixic acid. Penicillin G, ampicillin, and nitrofurantoin showed statistically significant losses of activity after 4 weeks. None of the chemotherapeutics tested showed significant loss in activity after 1 week. 相似文献
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Annette N. Chiang Mary Liang Antonio Dominguez-Meijide Caterina Masaracchia Jennifer L. Goeckeler-Fried Carly S. Mazzone David W. Newhouse Nathan M. Kendsersky Megan E. Yates Alexandra Manos-Turvey Patrick G. Needham Tiago F. Outeiro Peter Wipf Jeffrey L. Brodsky 《Bioorganic & medicinal chemistry》2019,27(1):79-91
Over-expression of the Hsp70 molecular chaperone prevents protein aggregation and ameliorates neurodegenerative disease phenotypes in model systems. We identified an Hsp70 activator, MAL1-271, that reduces α-synuclein aggregation in a Parkinson’s Disease model. We now report that MAL1-271 directly increases the ATPase activity of a eukaryotic Hsp70. Next, twelve MAL1-271 derivatives were synthesized and examined in a refined α-synuclein aggregation model as well as in an assay that monitors maturation of a disease-causing Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutant, which is also linked to Hsp70 function. Compared to the control, MAL1-271 significantly increased the number of cells lacking α-synuclein inclusions and increased the steady-state levels of the CFTR mutant. We also found that a nitrile-containing MAL1-271 analog exhibited similar effects in both assays. None of the derivatives exhibited cellular toxicity at concentrations up to 100?μm, nor were cellular stress response pathways induced. These data serve as a gateway for the continued development of a new class of Hsp70 agonists with efficacy in these and potentially other disease models. 相似文献
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Quantification of 22 phthalate metabolites in human urine 总被引:1,自引:0,他引:1
Silva MJ Samandar E Preau JL Reidy JA Needham LL Calafat AM 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,860(1):106-112
Phthalates are ubiquitous industrial chemicals with high potential for human exposure. Validated analytical methods to measure trace concentrations of phthalate metabolites in humans are essential for assessing exposure to phthalates. Previously, we developed a sensitive and accurate automated analytical method for measuring up to 16 phthalate metabolites in human urine by using on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography (HPLC)-electrospray ionization-tandem mass spectrometry. To include the measurement of seven additional analytes, including oxidative metabolites of diisononyl and diisodecyl phthalates, two chemicals used extensively in numerous consumer products, we used a novel nontraditional HPLC solvent gradient program. With this approach, we achieved adequate resolution and sensitivity for all 22 analytes with limits of detection in the low ng/mL range, without increasing the analytical run time. The method also has high accuracy with automatic recovery correction, high precision, and excellent sample throughput with minimal matrix effects. Although it is possible to measure these 22 phthalate metabolites with adequate precision and accuracy at sub-parts-per-billion levels, additional information, including toxicokinetic data, is needed to demonstrate the usefulness of these phthalate metabolites for exposure assessment purposes. 相似文献
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Oswaldo Keith Okamoto Ana Carolina SR Carvalho Luciana C Marti Ricardo Z Vêncio Carlos A Moreira-Filho 《Cancer cell international》2007,7(1):11
Background
Uncovering the molecular mechanism underlying expansion of hematopoietic stem and progenitor cells is critical to extend current therapeutic applications and to understand how its deregulation relates to leukemia. The characterization of genes commonly relevant to stem/progenitor cell expansion and tumor development should facilitate the identification of novel therapeutic targets in cancer. 相似文献89.
Procopiou PA Ford AJ Graves RH Hall DA Hodgson ST Lacroix YM Needham D Slack RJ 《Bioorganic & medicinal chemistry letters》2012,22(8):2730-2733
Synthesis and preliminary SAR of the N1 substituent of a novel series of indazole sulfonamide chemokine receptor 4 (CCR4) antagonist is reported. Compound 7r was identified for further development. 相似文献
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