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  • COA 100341

    Document Type:
    Certificate of Analysis
    Product Catalog Number:
    100341
  • Ten ERK-related proteins in three distinct classes associate with AP-1 proteins and/or AP-1 DNA 11431474

    We have identified seven ERK-related proteins ("ERPs"), including ERK2, that are stably associated in vivo with AP-1 dimers composed of diverse Jun and Fos family proteins. These complexes have kinase activity. We designate them as "class I ERPs." We originally hypothesized that these ERPs associate with DNA along with AP-1 proteins. We devised a DNA affinity chromatography-based analytical assay for DNA binding, the "nucleotide affinity preincubation specificity test recognition" (NAPSTER) assay. In this assay, class I ERPs do not associate with AP-1 DNA. However, several new "class II" ERPs do associate with DNA. p41 and p44 are ERK1/2-related ERPs that lack kinase activity and associate along with AP-1 proteins with AP-1 DNA. Class I ERPs and their associated kinase activity thus appear to bind AP-1 dimers when they are not bound to DNA and then disengage and are replaced by class II ERPs to form higher order complexes when AP-1 dimers bind DNA. p97 is a class III ERP, related to ERK3, that associates with AP-1 DNA without AP-1 proteins. With the exception of ERK2, none of the 10 ERPs appear to be known mitogen-activated protein kinase superfamily members.
    Document Type:
    Reference
    Product Catalog Number:
    Multiple
    Product Catalog Name:
    Multiple
  • Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels. 7768782

    Cefdinir is one of the few oral third generation cephalosporins that shows useful activity against nosocomial Gram-positive pathogens. For this reason the anti-staphylococcal potency of the new drug, alone or in combination with other drugs was further characterized. Against penicillin-resistant, oxacillin-susceptible Staphylococcus isolates, cefdinir demonstrated useful in-vitro activity. MIC90 values (in mg/L) were 0.25 for Staphylococcus aureus (30 strains), 0.06 for Staphylococcus epidermidis (24), 0.125 for Staphylococcus hominis (10), 0.5 for both Staphylococcus xylosus (15) and Staphylococcus capitis (11) and 4 for Staphylococcus saprophyticus (10), while Staphylococcus haemolyticus (12) was less susceptible with a MIC90 value of 32. Cefdinir activity was not adversely affected by several variables such as pH, inoculum size or the presence of serum or urine. The new cephem induced a PAE on all isolates studied: with S. aureus the extent of regrowth suppression ranged from 0.8 to 1 h, and with the other species from 0.5 (S. epidermidis) to 4.1 h (S. haemolyticus). Development of resistant strains was rare. At the highest level used (10 x MIC) mutants arose with a frequency of 6 x 10(-8) with S. haemolyticus and 2 x 10(-9) with S. epidermidis. The absence of a paradoxical effect of increasing concentrations of cefdinir on its bactericidal activity was confirmed up to a value of 500-fold the MICs. When cefdinir activity was assessed in association with ciprofloxacin, netilmicin, clarithromycin, fosfomycin, rifampicin, teicoplanin and vancomycin using the chequerboard and time-kill techniques, indifference predominated with all strains and in all combinations. Synergism was detected only in 11 out of a total of 175 tests performed by the chequerboard method. Using the time-kill technique cefdinir reacted synergically in 25 of 126 tests. Antagonism was never observed. S. aureus exposed to sub-inhibitory concentrations of cefdinir failed to grow on mannitol-salt agar and to produce haemolysins, but retained coagulase activity. Penicillinase production was also lost in about 17% of the survivors. Hydrophobicity changes were detected in all species tested with the exception of S. saprophyticus.
    Document Type:
    Reference
    Product Catalog Number:
    25-006