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202 results on '"Tong, Carmen"'

2. Screening for inhibitors of Staphylococcal Sortase A as novel anti-infective agents

Author

Tong, Carmen

Subjects
616.9, QP501 Animal biochemistry, RB Pathology
Abstract

Staphylococcus aureus is a Gram-positive human pathogen that has developed resistance to all traditionally used antibiotics. Sortase A (SrtA) is a 'house-keeping' enzyme present in a number of Gram-positive organisms including S. aureus that is responsible for the covalent anchoring of proteins to the cell wall through the recognition of a highly conserved LPXTG motif. Many of the proteins it anchors are involved in virulence and immune evasion suggesting that it is an attractive target for potential anti-infective therapies. Moreover, as SrtA is not vital for bacterial growth or survival, inhibition may not select for the development of drug-resistance, unlike conventional antibiotics. This study evaluated different assays to assay SrtA activity and includes an in vitro Fluorescence Resonance Energy Transfer (FRET) assay using purified recombinant SrtA protein and an in vivo whole cell-based assay that measured SrtA-mediated anchoring of Gaussia luciferase (GLuc) in S. aureus. A further in vivo assay was evaluated, which measured SrtA activity using fluorescence as a reporter and analysis by flow cytometry and structured illumination microscopy. In this study three novel small molecules were identified as potential inhibitors of SrtA using in silico computational docking and SAR analysis; NCC-00014270, NCC-00076932 and NCC-00032784. These compounds were shown to inhibit SrtA in vitro in a dose-dependent manner with IC50s of 140 ± 24.6 µM, 172 ± 28.1 µM and 628 ± 122 µM respectively and were shown to act as competitive inhibitors of the SrtA. With the use of an in vivo reporter, it was shown that all three compounds negatively affected SrtA-mediated anchoring in S. aureus whole cells. Moreover, the cytotoxicity of these lead compounds against eukaryotic cells was assessed. Overall, these data suggest that two of the three lead compounds were potential 'hit' molecules for further structural modification for increased inhibitory activity against SrtA.

Published
2018

19. Facilitating Mental Health Treatment Through Proactive Screening and Concierge Services in the Workplace.

Author

Fragala, Maren S., Tong, Carmen H., Hunter, Jennifer L., Jelovic, Nicole A., Hayward, Joanna I., Carr, Susan, Kim, Paul M., Peters, Matthew E., and Birse, Charles E.

Subjects
*MENTAL illness treatment, *PSYCHIATRIC diagnosis, *EVALUATION of human services programs, *CONFIDENCE intervals, *MEDICAL screening, *HUMAN services programs, *T-test (Statistics), *QUESTIONNAIRES, *CHI-squared test, *DESCRIPTIVE statistics, *KAPLAN-Meier estimator, *DATA analysis software, *MENTAL health services, *INDUSTRIAL relations, *PROPORTIONAL hazards models
Abstract

A proactive employer-sponsored mental health program facilitated linkage to mental health services and prescription medications among participants who connected with a care concierge. Objective: The aim of this study is to determine if a proactive employer-sponsored mental health program closed gaps in detection and treatment of mental health conditions. Methods: Of n = 56,442 eligible, n = 8170 (14.5%) participated in the optional screening. Participants with mental health risk were offered care concierge services including support, care planning, and connection to care. Difference in behavioral health care utilization, diagnoses, and prescriptions were evaluated postintervention through claims analysis. Results: Compared with controls (n = 2433), those receiving concierge services (n = 369) were more likely to fill mental health prescriptions (adjusted hazards ratio [HR], 1.2; 1.0–1.5; P = 0.042), use professional mental health services (adjusted HR, 1.4; 1.1–1.8; P = 0.02), and use new mental health services (adjusted HR, 1.9; 1.2–2.8; P = 0.004) in the following 6 months. Conclusions: This proactive mental health program with care concierge services identified risk, connected individuals to mental health care, and facilitated mental health treatment, among program participants. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Abstract 1715: First in class inhibitors of ERAP1 have the potential to be a transformative immunotherapy in oncology

Author

Leishman, Andrew, primary, Poynton, Fergus, additional, Ternette, Nicola, additional, Lori, Elisa, additional, de Almeida, Camila, additional, Leonard, Henry, additional, Reeves, Emma, additional, James, Edd, additional, Clark, Kristopher, additional, Tong, Carmen, additional, Shiers, Jason, additional, Quibell, Martin, additional, and Joyce, Peter Ian, additional

Published
2021
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24. Gene variants associated with deep vein thrombosis

Author

Bezemer, Irene D., Bare, Lance A., Doggen, Carine J.M., Tong, Carmen, Arellano, Andre R., Rowland, Charles M., Young, Bradford A., Reitsma, Pieter H., Devlin, James J., Rosendaal, Frits R., and Catanese, Joseph

Subjects
Venous thrombosis -- Health aspects, Venous thrombosis -- Causes of, Genes -- Research, Genetic variation -- Risk factors
Abstract

A study to ascertain whether gene variation could be associated as a cause of deep vein thrombosis (DVT) was conducted. Results showed that certain genetic variation was associated with DVT.

Published
2008

27. Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice

Author

Gregoire, Francine M., Zhang, Qin, Smith, Steven J., Tong, Carmen, Ross, David, Lopez, Henry, and West, David B.

Subjects
Obesity -- Physiological aspects, Mice -- Food and nutrition, Gene expression -- Analysis, Biological sciences
Abstract

The effects of high-fat feeding on the development of obesity were evaluated in intercellular adhesion molecule-1 (ICAM-1) knockout and C57BL/6J (B6) male mice fed a high-fat diet for [less than or equal to] 50 days. Serum and tissues were collected at baseline and after 1, 11, and 50 days on the diet. After 11 days on the diet, ICAM-1-deficient, but not B6, mice developed fatty livers and showed a significant increase in inguinal fat pad weight. At day 50, ICAM-1-deficient mice weighed less, and their adiposity index and circulating leptin levels were significantly lower than those of B6 controls. To better understand the early differential response to the diet, liver gene expression was analyzed at three time points by use of Affymetrix GeneChips. In both strains, a similar pattern of gene expression was detected in response to the high-fat diet. However, sterol regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were significantly induced in ICAM-1-deficient livers, suggesting that these genes and their associated pathways may be involved in the acute diet response observed in the knockout mice. intercellular adhesion molecule-1 knockout mice; obesity; dyslipidemia; steatosis; microarray

Published
2002

29. Polymorphisms and Noncardioembolic Stroke in Three Case-Control Studies

Author

Luke, May M., Berger, Klaus, Rowland, Charles M., Catanese, Joseph J., Tong, Carmen H., Ross, David A., Garcia, Veronica, Kuhlenbaeumer, Gregor, Ringelstein, Bernd E., Pullinger, Clive R., Malloy, Mary J., Deedwania, Prakash, Ellis, Stephen G., Kane, John P., Devlin, James J., Lalouschek, Wolfgang, and Mannhalter, Christine

Published
2012
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30. 446 Immunopeptidome changes mediated by a novel ERAP1 inhibitor leads to tumor growth inhibition

Author

Joyce, Peter, primary, Young, Lesley, additional, Quibell, Martin, additional, Shiers, Jason, additional, Tong, Carmen, additional, Clark, Kristopher, additional, James, Edd, additional, Reeves, Emma, additional, Remtulla, Alihussein, additional, Leonard, Henry, additional, Almeida, Camila de, additional, Lori, Elisa, additional, Ternette, Nicola, additional, Poynton, Fergus, additional, and Leishman, Andrew, additional

Published
2020
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31. Abstract 5551: Potent oral ERAP1 inhibitors modify the immunopeptidome in vivo and are novel immunotherapy agents

Author

Ware, Jamie, primary, McIntyre, Patrick, additional, Clark, Kristopher, additional, Tong, Carmen, additional, Shiers, Jason, additional, Lori, Elisa, additional, de Almeida, Camila, additional, Reeves, Emma, additional, Leonard, Henry, additional, Remtulla, Alihussein, additional, Ford, Michael, additional, Ternette, Nicola, additional, Poynton, Fergus, additional, James, Edd, additional, Young, Lesley, additional, Quibell, Martin, additional, and Joyce, Peter I., additional

Published
2020
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40. Evaluation of novel fluorinated puromycin analogues as potential candidates for PET imaging of protein synthesis

Author

Betts, Helen M., Sephton, Selena Milicevic, Tong, Carmen, Awais, Ramla, Hill, Philip J., Perkins, A.C., and Aigbirhio, Franklin I.

Abstract

There is currently no ideal radiotracer for imaging protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18 labelled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabelled with the short half-life positron emitter carbon-11 which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis which identified fluoroethyl analogue (7b) as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in modest radiochemical yield 2±0.6% and excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature.

Published
2016

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