Davis L

References (5)

Title : A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events - Martin-Castellanos_2005_Curr.Biol_15_2056
Author(s) : Martin-Castellanos C , Blanco M , Rozalen AE , Perez-Hidalgo L , Garcia AI , Conde F , Mata J , Ellermeier C , Davis L , San-Segundo P , Smith GR , Moreno S
Ref : Current Biology , 15 :2056 , 2005
Abstract : Meiosis is a specialized form of cell division by which sexually reproducing diploid organisms generate haploid gametes. During a long prophase, telomeres cluster into the bouquet configuration to aid chromosome pairing, and DNA replication is followed by high levels of recombination between homologous chromosomes (homologs). This recombination is important for the reductional segregation of homologs at the first meiotic division; without further replication, a second meiotic division yields haploid nuclei. In the fission yeast Schizosaccharomyces pombe, we have deleted 175 meiotically upregulated genes and found seven genes not previously reported to be critical for meiotic events. Three mutants (rec24, rec25, and rec27) had strongly reduced meiosis-specific DNA double-strand breakage and recombination. One mutant (tht2) was deficient in karyogamy, and two (bqt1 and bqt2) were deficient in telomere clustering, explaining their defects in recombination and segregation. The moa1 mutant was delayed in premeiotic S phase progression and nuclear divisions. Further analysis of these mutants will help elucidate the complex machinery governing the special behavior of meiotic chromosomes.
ESTHER : Martin-Castellanos_2005_Curr.Biol_15_2056
PubMedSearch : Martin-Castellanos_2005_Curr.Biol_15_2056
PubMedID: 16303567
Gene_locus related to this paper: schpo-SPBPB2B2.02

Title : Cholinesterase. Its significance in anaesthetic practice. - Davis_1997_Anaesthesia_52_244
Author(s) : Davis L , Britten JJ , Morgan M
Ref : Anaesthesia , 52 :244 , 1997
Abstract : Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its role in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.
ESTHER : Davis_1997_Anaesthesia_52_244
PubMedSearch : Davis_1997_Anaesthesia_52_244
PubMedID: 9124666

Title : Pharmacological activity and safety profile of P10358, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease - Smith_1997_J.Pharmacol.Exp.Ther_280_710
Author(s) : Smith CP , Bores GM , Petko W , Li M , Selk DE , Rush DK , Camacho F , Winslow JT , Fishkin R , Cunningham DM , Brooks KM , Roehr J , Hartman HB , Davis L , Vargas HM
Ref : Journal of Pharmacology & Experimental Therapeutics , 280 :710 , 1997
Abstract : 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-1(H)-indol-5-yl methyl carbamate (P10358) is a potent, reversible acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral and parental administration in rats and mice. P10358 is a 2.5 times more potent acetylcholinesterase inhibitor than THA in vitro (IC50 = 0.10 +/- 0.02 microM vs. IC50 = 0.25 +/- 0.03 microM). It also inhibits butyrylcholinesterase activity as potently as THA (IC50 = 0.08 +/- 0.05 microM vs. IC50 = 0.07 +/- 0.01 microM). Ex vivo, P10358 (0.2 - 20 mg/kg, p.o.) produced dose-dependent inhibition of brain acetylcholinesterase activity. At 10 and 20 mg/ kg, it produced profound and long-lasting hypothermia in mice. P10358 enhanced performance in rats in a step-down passive avoidance task (0.62 and 1.25 mg/kg) and in a social recognition paradigm (0.32, 0.64 and 1.25 mg/kg) in mice. It reversed scopolamine-induced deficits in the Morris Water maze in rats (1.25 and 2.5 mg/kg) and a higher dose elevated striatal homovanillic acid levels. These behavioral and biochemical effects are consistent with central cholinergic stimulation. Hemodynamic studies in the rat demonstrated a 16-fold separation between behaviorally active doses (1.25 mg/kg) and those that elevated arterial pressure (20 mg/kg). Lethality in rats occurred at an oral dose of 80 mg/kg, but not at lower doses. Chemically, P10358 is an N-aminoindole and may not have the hepatotoxic liability associated with aminoacridine structure of tacrine. P10358 had weak affinity (>10 microM) at a variety of aminergic and peptidergic receptors and uptake carriers. These properties suggest that P10358 may be a safe and promising symptomatic treatment for Alzheimer's disease.
ESTHER : Smith_1997_J.Pharmacol.Exp.Ther_280_710
PubMedSearch : Smith_1997_J.Pharmacol.Exp.Ther_280_710
PubMedID: 9023283

Title : Pharmacological evaluation of novel Alzheimer's disease therapeutics: acetylcholinesterase inhibitors related to galanthamine - Bores_1996_J.Pharmacol.Exp.Ther_277_728
Author(s) : Bores GM , Huger FP , Petko W , Mutlib AE , Camacho F , Rush DK , Selk DE , Wolf V , Kosley RW, Jr. , Davis L , Vargas HM
Ref : Journal of Pharmacology & Experimental Therapeutics , 277 :728 , 1996
Abstract : Acetylcholinesterase (AChE) inhibitors from several chemical classes have been tested for the symptomatic treatment of Alzheimer's disease; however, the therapeutic success of these compounds has been limited. Recently, another AChE inhibitor, galanthamine hydrobromide (GAL), has shown increased clinical efficacy and safety. Using biochemical, behavioral and pharmacokinetic analyses, this report compares GAL with two of its analogs, 6-O-acetyl-6-O-demethylgalanthamine hydrochloride (P11012) and 6-O-demethyl-6-O[(adamantan-1-yl)-carbonyl]galanthamine hydrochloride (P11149), for their therapeutic potential. P11012 and P11149 were found to be potent, competitive and selective inhibitors of AChE, demonstrating central cholinergic activity, behavioral efficacy and safety. P11012 and P11149, though pharmacokinetic analyses, were shown to act as pro-drugs, yielding significant levels of 6-O-demethylgalanthamine. In vitro, 6-O-demethylgalanthamine was 10- to 20-fold more potent than GAL as an inhibitor of AChE, and it demonstrated greater selectivity for inhibition of AChE vs. butyrylcholinesterase. Like GAL, both P11012 and P11149 showed central cholinergic activity biochemically, by significantly inhibiting rat brain AChE; physiologically, by causing hypothermia; and behaviorally, by attenuating scopolamine-induced deficits in passive avoidance. In addition, GAL, P11012 and P11149 enhanced step-down passive avoidance, another measure of behavioral efficacy. By comparing efficacious doses with primary overt effects, P11012 and P11149 had better oral therapeutic indices than GAL. Oral pharmacokinetic analyses of GAL, P11012 and P11149 revealed differences. Although P11012 and P11149 exhibited similar area under the curve values, 191149 had slower, lower and more sustained concentration maximum levels. P11012 and GAL rapidly reached their concentration maximums, but GAL, in brain had the highest area under the curve and concentration maximum. Because of its composite profile, including duration of action, oral therapeutic index and pharmacokinetics, P11149 is considered the better therapeutic candidate for the treatment of Alzheimer's disease.
ESTHER : Bores_1996_J.Pharmacol.Exp.Ther_277_728
PubMedSearch : Bores_1996_J.Pharmacol.Exp.Ther_277_728
PubMedID: 8627552

Title : Mivacurium and prolonged neuromuscular block [letter\; comment] [see comments] -
Author(s) : Davis L
Ref : British Journal of Anaesthesia , 75 :374 , 1995
PubMedID: 7547070