Miller MD

References (8)

Title : Using High-Throughput Screening to Evaluate Perturbations Potentially Linked to Neurobehavioral Outcomes: A Case Study Using Publicly Available Tools on FDA Batch-Certified Synthetic Food Dyes - Pham_2021_Chem.Res.Toxicol__
Author(s) : Pham N , Miller MD , Marty M
Ref : Chemical Research in Toxicology , : , 2021
Abstract : There is growing evidence from human and animal studies indicating an association between exposure to synthetic food dyes and adverse neurobehavioral outcomes in children. However, data gaps persist for potential mechanisms by which the synthetic food dyes could elicit neurobehavioral impacts. We developed an approach to evaluate seven US FDA-batch-certified food dyes using publicly available high-throughput screening (HTS) data from the US EPA's Toxicity Forecaster to assess potential underlying molecular mechanisms that may be linked to neurological pathway perturbations. The dyes were screened through 270 assays identified based on whether they had a neurological-related gene target and/or were mapped to neurodevelopmental processes or neurobehavioral outcomes, and were conducted in brain tissue, targeted specific hormone receptors, or targeted oxidative stress and inflammation. Some results provided support for neurological impacts found in human and animal studies, while other results showed a lack of correlation with in vivo findings. The azo dyes had a range of activity in assays mapped to G-protein-coupled receptors and were active in assays targeting dopaminergic, serotonergic, and opioid receptors. Assays mapped to nuclear receptors (androgen, estrogen, and thyroid hormone) also exhibited activity with the food dyes. Other molecular targets included the aryl hydrocarbon receptor, acetylcholinesterase, and monoamine oxidase. The Toxicological Prioritization Index tool was used to visualize the results of the Novascreen assays. Our results highlight certain limitations of HTS assays but provide insight into potential underlying mechanisms of neurobehavioral effects observed in in vivo animal toxicology studies and human clinical studies.
ESTHER : Pham_2021_Chem.Res.Toxicol__
PubMedSearch : Pham_2021_Chem.Res.Toxicol__
PubMedID: 34705446

Title : Functional and structural characterization of a thermostable acetyl esterase from Thermotoga maritima - Levisson_2012_Proteins_80_1545
Author(s) : Levisson M , Han GW , Deller MC , Xu Q , Biely P , Hendriks S , Ten Eyck LF , Flensburg C , Roversi P , Miller MD , McMullan D , von Delft F , Kreusch A , Deacon AM , Van der Oost J , Lesley SA , Elsliger MA , Kengen SW , Wilson IA
Ref : Proteins , 80 :1545 , 2012
Abstract : TM0077 from Thermotoga maritima is a member of the carbohydrate esterase family 7 and is active on a variety of acetylated compounds, including cephalosporin C. TM0077 esterase activity is confined to short-chain acyl esters (C2-C3), and is optimal around 100degC and pH 7.5. The positional specificity of TM0077 was investigated using 4-nitrophenyl--D-xylopyranoside monoacetates as substrates in a -xylosidase-coupled assay. TM0077 hydrolyzes acetate at positions 2, 3, and 4 with equal efficiency. No activity was detected on xylan or acetylated xylan, which implies that TM0077 is an acetyl esterase and not an acetyl xylan esterase as currently annotated. Selenomethionine-substituted and native structures of TM0077 were determined at 2.1 and 2.5 resolution, respectively, revealing a classicalpha/beta-hydrolase fold. TM0077 assembles into a doughnut-shaped hexamer with small tunnels on either side leading to an inner cavity, which contains the six catalytic centers. Structures of TM0077 with covalently bound phenylmethylsulfonyl fluoride and paraoxon were determined to 2.4 and 2.1 , respectively, and confirmed that both inhibitors bind covalently to the catalytic serine (Ser188). Upon binding of inhibitor, the catalytic serine adopts an altered conformation, as observed in other esterase and lipases, and supports a previously proposed catalytic mechanism in which Ser hydroxyl rotation prevents reversal of the reaction and allows access of a water molecule for completion of the reaction.
ESTHER : Levisson_2012_Proteins_80_1545
PubMedSearch : Levisson_2012_Proteins_80_1545
PubMedID: 22411095
Gene_locus related to this paper: thema-TM0077

Title : Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy - Reynolds_2011_Arch.Gen.Psychiatry_68_51
Author(s) : Reynolds CF, 3rd , Butters MA , Lopez O , Pollock BG , Dew MA , Mulsant BH , Lenze EJ , Holm M , Rogers JC , Mazumdar S , Houck PR , Begley A , Anderson S , Karp JF , Miller MD , Whyte EM , Stack J , Gildengers A , Szanto K , Bensasi S , Kaufer DI , Kamboh MI , DeKosky ST
Ref : Arch Gen Psychiatry , 68 :51 , 2011
Abstract : CONTEXT: Cognitive impairment in late-life depression is a core feature of the illness. OBJECTIVE: To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. DESIGN: Randomized, double-blind, placebo-controlled maintenance trial. SETTING: University clinic. PARTICIPANTS: One hundred thirty older adults aged 65 years and older with recently remitted major depression. INTERVENTIONS: Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES: Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. RESULTS: Donepezil and antidepressant therapy temporarily improved global cognition (treatment x time interaction, F(2),(2)(1)(6) = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment x time interaction, F(2),(1)(3)(7) = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank chi(2) = 3.97; P = .05; hazard ratio = 2.09 [95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression. CONCLUSIONS: Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. TRIAL REGISTRATION: Identifier: NCT00177671.
ESTHER : Reynolds_2011_Arch.Gen.Psychiatry_68_51
PubMedSearch : Reynolds_2011_Arch.Gen.Psychiatry_68_51
PubMedID: 21199965

Title : Crystal structure of homoserine O-succinyltransferase from Bacillus cereus at 2.4 A resolution -
Author(s) : Zubieta C , Krishna SS , McMullan D , Miller MD , Abdubek P , Agarwalla S , Ambing E , Astakhova T , Axelrod HL , Carlton D , Chiu HJ , Clayton T , Deller M , DiDonato M , Duan L , Elsliger MA , Grzechnik SK , Hale J , Hampton E , Han GW , Haugen J , Jaroszewski L , Jin KK , Klock HE , Knuth MW , Koesema E , Kumar A , Marciano D , Morse AT , Nigoghossian E , Oommachen S , Reyes R , Rife CL , van den Bedem H , Weekes D , White A , Xu Q , Hodgson KO , Wooley J , Deacon AM , Godzik A , Lesley SA , Wilson IA
Ref : Proteins , 68 :999 , 2007
PubMedID: 17546672
Gene_locus related to this paper: bacce-BC4730

Title : Crystal structure of an alpha\/beta serine hydrolase (YDR428C) from Saccharomyces cerevisiae at 1.85 A resolution -
Author(s) : Arndt JW , Schwarzenbacher R , Page R , Abdubek P , Ambing E , Biorac T , Canaves JM , Chiu HJ , Dai X , Deacon AM , DiDonato M , Elsliger MA , Godzik A , Grittini C , Grzechnik SK , Hale J , Hampton E , Han GW , Haugen J , Hornsby M , Klock HE , Koesema E , Kreusch A , Kuhn P , Jaroszewski L , Lesley SA , Levin I , McMullan D , McPhillips TM , Miller MD , Morse A , Moy K , Nigoghossian E , Ouyang J , Peti WS , Quijano K , Reyes R , Sims E , Spraggon G , Stevens RC , van den Bedem H , Velasquez J , Vincent J , von Delft F , Wang X , West B , White A , Wolf G , Xu Q , Zagnitko O , Hodgson KO , Wooley J , Wilson IA
Ref : Proteins , 58 :755 , 2005
PubMedID: 15624212
Gene_locus related to this paper: yeast-YDR428C

Title : Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients - Solai_2002_J.Clin.Psychopharmacol_22_481
Author(s) : Solai LK , Pollock BG , Mulsant BH , Frye RF , Miller MD , Sweet RA , Kirshner M , Sorisio D , Begley A , Reynolds CF, 3rd
Ref : J Clin Psychopharmacol , 22 :481 , 2002
Abstract : This study was performed in elderly patients (1) to assess the degree to which CYP2D6 mediated metabolism of debrisoquine at baseline determines plasma concentration to dose quotients for nortriptyline or paroxetine after 4 weeks of treatment, and (2) to compare the effects of nortriptyline and paroxetine on debrisoquine metabolism after 6 weeks of treatment. CYP2D6 activity was estimated in 66 subjects (71.4 +/- 7.2 years) before initiating treatment and again after 6 weeks of treatment with either nortriptyline or paroxetine under randomized, double-blind conditions according to a standard protocol. CYP2D6 activity was estimated by the debrisoquine recovery ratio in a 6- to 8-hour urine sample collected after oral administration of 10 mg debrisoquine sulfate. Nortriptyline and paroxetine plasma concentrations were obtained weekly. Baseline debrisoquine recovery ratio values were significantly correlated with the plasma concentration to dose quotient at 4 weeks for both nortriptyline ( = -0.75, = 0.0001, N = 29) and paroxetine ( = -0.50, = 0.003, N = 33). Treatment with either nortriptyline or paroxetine was associated with a significant decrease in the median debrisoquine recovery ratio, reflecting inhibition of CYP2D6 metabolism. The percent decrease associated with nortriptyline was significantly smaller than that with paroxetine ( < 0.0001). None of the patients treated with nortriptyline but 19 of the 32 extensive metabolizers treated with paroxetine were converted to phenotypic poor metabolic status. Our observations of CYP2D6 inhibition are consistent with data and results obtained in younger healthy volunteers. The significant correlations between baseline debrisoquine recovery ratio and the plasma concentrations to dose quotients at 4 weeks for both nortriptyline and paroxetine are consistent with CYP2D6 playing a major role in the metabolism of both drugs. CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine.
ESTHER : Solai_2002_J.Clin.Psychopharmacol_22_481
PubMedSearch : Solai_2002_J.Clin.Psychopharmacol_22_481
PubMedID: 12352271

Title : Biochemical and behavioral evidence for muscarinic autoreceptors in the CNS - Hoss_1990_Brain.Res_517_195
Author(s) : Hoss WP , Messer WS, Jr. , Monsma FJ, Jr. , Miller MD , Ellerbrock BR , Scranton T , Ghodsi-Hovsepian S , Price MA , Balan S , Mazloum Z , Bohnett M
Ref : Brain Research , 517 :195 , 1990
Abstract : Muscarinic autoreceptors of the M2 subclass were examined in rat forebrain using a number of different methodologies, including receptor autoradiography and image analysis, regulation of acetylcholine release, phosphoinositide turnover, low-Km GTP hydrolysis, and behavioral analysis. The relatively minor population of M2 receptors in coronal sections was visualized by autoradiography and image analysis using [3H]quinuclidinyl benzilate in the presence of a concentration of pirenzepine that blocked most of M1 (and M4) receptors. The highest densities of M2 receptors in forebrain regions were found in the outer layers of the cortex, CA1 region of the hippocampus and striatum. The M2-, but not M1-selective antagonists were able to block the oxotremorine-induced attenuation of acetylcholine release in forebrain synaptosomes. Low concentrations of the M2-selective antagonist gallamine increased phosphoinositide turnover, which is thought to be an M1 postsynaptic response in the forebrain, in brain slices by a Ca2(+)-dependent mechanism. The M2-selective agonist oxotremorine produced a substantial stimulation of low-Km GTPase in cortical membranes, suggesting that M2 forebrain receptors are efficiently coupled to G-proteins in the cortex. Behavioral signs of cholinergic stimulation were observed after intracerebroventricular injections of M2-, but not M1-selective antagonists. It is suggested that a minor population of forebrain M2 receptors regulates acetylcholine release by a mechanism that includes coupling through G-proteins presynaptically at synapses for which the postsynaptic response involves phosphoinositide turnover. Selective blockade of these receptors produces both biochemical and behavioral signs of acetylcholine release.
ESTHER : Hoss_1990_Brain.Res_517_195
PubMedSearch : Hoss_1990_Brain.Res_517_195
PubMedID: 2375989

Title : Intrahippocampal injections of gallamine impair learning of a memory task - Messer_1988_Neurosci.Lett_89_367
Author(s) : Messer WS, Jr. , Miller MD
Ref : Neuroscience Letters , 89 :367 , 1988
Abstract : Recent evidence has suggested that gallamine may act as an antagonist on presynaptic M2 muscarinic receptors which regulate acetylcholine release. The possibility that gallamine may potentiate learning by enhancing the release of acetylcholine was examined using a behavioral paradigm known to depend on cholinergic activity. Rats were cannulated bilaterally for intrahippocampal (i.h.) injections and adapted to a T-maze before the series of injections was initiated. The effects of bilateral i.h. injections of saline or gallamine (10 micrograms total) were examined on the learning of a win-stay, paired-run task in a T-maze. During the first few sessions, both saline- and gallamine-treated animals achieved below 50% correct responses. Both groups of animals gradually improved performance on the task although, contrary to expectations, gallamine-treated animals did not learn as rapidly as saline-injected animals. To verify the deleterious effects of gallamine on learning, the experiment was repeated using a second group of rats. Similar results were observed; gallamine-treated animals learned to perform the task at a slower rate than the saline-injected controls. The results suggest that treatment strategies with cholinomimetics may impair, rather than enhance performance after long-term administrations.
ESTHER : Messer_1988_Neurosci.Lett_89_367
PubMedSearch : Messer_1988_Neurosci.Lett_89_367
PubMedID: 3419634