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Biomedical subjects

Lisa Moore

Publications and source records attributed to Lisa Moore.

8 recordsLinked to original sources
PubMed2006

Chemical genetics reveals an RGS/G-protein role in the action of a compound.

We report here on a chemical genetic screen designed to address the mechanism of action of a small molecule. Small molecules that were active in models of urinary incontinence were tested on the nematode Caenorhabditis elegans, and the resulting phenotypes were used as readouts in a genetic screen to identify possible molecular targets. The mutations giving resistance to compound were found to affect members of the RGS protein/G-protein complex. Studies in mammalian systems confirmed that the small molecules inhibit muscarinic G-protein coupled receptor (GPCR) signaling involving G-alphaq (G-protein alpha subunit). Our studies suggest that the small molecules act at the level of the RGS/G-alphaq signaling complex, and define new mutations in both RGS and G-alphaq, including a unique hypo-adapation allele of G-alphaq. These findings suggest that therapeutics targeted to downstream components of GPCR signaling may be effective for treatment of diseases involving inappropriate receptor activation.

Animals↗
PubMed2005

Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5- methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities.

Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR alpha/gamma dual agonist that shows potent activity in vitro at human PPARalpha (EC(50) = 320 nM) and PPARgamma(EC(50) = 110 nM). Compound 2 shows excellent efficacy for lowering glucose, insulin, triglycerides, and free fatty acids in genetically obese, severely diabetic db/db mice and has a favorable ADME profile. Compound 2 is currently in clinical development for the treatment of type 2 diabetes and dyslipidemia.

Adipocytes↗
PubMed2005

The impact of a police drug crackdown on drug injectors' ability to practice harm reduction: a qualitative study.

This paper employs qualitative methods to explore the ramifications of a police drug crackdown on drug injectors' ability to practice harm reduction. Between August and December 2000, we conducted open-ended interviews with 40 illicit-drug-injecting residents of a New York City police precinct undergoing a crackdown. Interview topics included participants' experiences with police in the precinct and their drug use practices. Grounded theory methods were used to analyze resulting transcripts. Because place emerged as a salient analytic category, we also drew on elements of social geography to interpret results. The analysis suggests that particular crackdown tactics, notably frequent police searches of participants' bodies and elevated surveillance of the precinct's public spaces, reconfigured participants' experiences of their bodies and the public spaces comprising the precinct in ways that adversely affected their capacity to engage in harm reduction. Frequent police searches, for example, discouraged participants from carrying the injection equipment they needed to ensure that they could inject with a sterile syringe. Constant monitoring of local public spaces made it difficult for homeless women and men to inject safely. Simultaneously, participants expressed support for police actions that reduced public drug activity. Given these findings, we recommend the implementation of strategies, designed by partnerships of community groups and governmental and non-governmental organizations, which reduce public drug activity without imperiling injectors' health. Possible strategies include improving access to treatment and establishing safe injection spaces.

Adolescent↗
PubMed2004

Detection of chronic kidney disease with laboratory reporting of estimated glomerular filtration rate and an educational program.

BACKGROUND: Serum creatinine concentration is an inadequate screening test for chronic kidney disease, especially in elderly patients. We hypothesized that laboratory reporting of estimated glomerular filtration rate (GFR) accompanied with an educational intervention would improve recognition of chronic kidney disease (CKD). METHODS: We conducted a before-and-after study at an outpatient family medicine practice. Patients 65 years or older for whom a Cockcroft-Gault GFR could be calculated from their medical record were included. The intervention consisted of automatic reporting of estimated GFR by the hospital laboratory along with an educational intervention directed toward the primary care physicians. The primary outcome was the recognition of CKD (defined as a Cockroft-Gault GFR <60 mL/min [<1.0 mL/s]) by the primary care physician. Factors associated with the recognition of CKD were also determined. RESULTS: The study population comprised 324 patients. Prior to the study intervention, 22.4% of patients with CKD were recognized, which increased to 85.1% after the intervention. Before the intervention, recognition was more likely in male subjects (odds ratio, 4.3; 95% confidence interval, 1.9-9.8) and patients with diabetes (odds ratio, 3.4; 95% confidence interval, 1.6-7.6). These associations were no longer statistically significant after the intervention. CONCLUSION: Laboratory reporting of estimated GFR coupled with an educational program markedly improves the recognition of CKD in the primary care setting.

Aged↗
PubMed2004

Characterizing perceived police violence: implications for public health.

Despite growing recognition of violence's health consequences and the World Health Organization's recent classification of police officers' excessive use of force as a form of violence, public health investigators have produced scant research characterizing police-perpetrated abuse. Using qualitative data from a study of a police drug crackdown in 2000 in 1 New York City police precinct, we explored 40 injection drug using and 25 non-drug using precinct residents' perceptions of and experiences with police-perpetrated abuse. Participants, particularly injection drug users and non-drug using men, reported police physical, psychological, and sexual violence and neglect; they often associated this abuse with crackdown-related tactics and perceived officer prejudice. We recommend that public health research address the prevalence, nature, and public health implications of police violence.

Adult↗
PubMed1999

Asymmetric Synthesis of Conformationally Restricted L-Arginine Analogues as Active Site Probes of Nitric Oxide Synthase.

Using the catalytic asymmetric Sharpless carbamate aminohydroxylation, conformationally restricted L-arginine and L-homoarginine derivatives (5-8) were prepared in good enantiomeric excess to investigate the binding requirements of L-arginine-based compounds with nitric oxide synthase. The L-arginine derivatives (5 and 6) inhibited both the inducible and neuronal isoforms of nitric oxide synthase with little isoform selectivity (5, IC(50) = 42 and 144 &mgr;M, 6, 8 and 12 &mgr;M, respectively). The guanidine-containing compound (5) did not act as a nitric oxide producing substrate for nitric oxide synthase. The ability of these compounds to interact with the enzyme supports the idea that L-arginine-based inhibitors bind to the enzyme in a folded conformation. The L-homoarginine derivatives (7 and 8) did not interact with the enzyme as either substrates or inhibitors. The two-carbon L-arginine homologue (9), prepared from L-phenylalanine, demonstrated the greatest isoform selective inhibition of the compounds examined (IC(50)(iNOS) = 19 and IC(50)(nNOS) = 147 &mgr;M, IC(50)(nNOS)/IC(50)i(NOS) = 7.7). These results suggest isoform selective inhibition may be related to the folded conformations required for binding of these higher L-arginine homologues.

Journal Article↗
PubMedDate not supplied

Intravesical instillation of dilute formalin for the treatment of severe hemorrhagic emphysematous cystitis in a diabetic dog.

Intravesical formalin is a known treatment for control of hemorrhagic cystitis caused by multiple etiologies in humans and dogs. This case report documents the successful use of intravesical formalin for the treatment of severe hemorrhagic cystitis that occurred secondary to emphysematous cystitis in a diabetic dog. In addition, a review of emphysematous cystitis and the use of intravesical formalin in human and veterinary medicine is discussed. Formalin instillation into the urinary bladder is an option for life-threatening, refractory cases of hemorrhagic cystitis; but clinicians must be familiar with the proper technique and be aware of potential complications prior to its use.

Animals↗