The Experts below are selected from a list of 915 Experts worldwide ranked by ideXlab platform
Robert B. Diasio - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of Pyrimidine analogues and their nucleosides
Pharmacology & Therapeutics, 2002Co-Authors: George C. Daher, Barry E. Harris, Robert B. DiasioAbstract:Abstract The Pyrimidine antiMetabolite drugs consist of base and nucleoside analogues of the naturally occurring Pyrimidines uracil, thymine and cytosine. As is typical of antiMetabolites, these drugs have a strong structural similarity to endogenous nucleic acid precursors. The structural differences are usually substitutions at one of the carbons in the Pyrimidine ring itself or substitutions at one of the hydrogens attached to the ring of the Pyrimidine or sugar (ribose or deoxyribose). Despite the differences noted above, these analogues, can still be taken up into cells and then metabolized via anabolic or catabolic pathways used by endogenous Pyrimidines. Cytotoxicity results when the antiMetabolite either is incorporated in place of the naturally Pyrimidine Metabolite into a key molecule (such as RNA or DNA) or competes with the naturally occurring Pyrimidine Metabolite for a critical enzyme. There are four Pyrimidine antiMetabolites that are currently used extensively in clinical oncology. These include the fluoroPyrimidines, fluorouracil and fluorodeoxyuridine, and the cytosine analogues, cytosine arabinoside and azacytidine.
Augusto A Litonjua - One of the best experts on this subject based on the ideXlab platform.
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plasma Metabolite profiles in children with current asthma
Clinical & Experimental Allergy, 2018Co-Authors: Rachel S Kelly, Joanne E Sordillo, Jessica Laskysu, Amber Dahlin, Wei Perng, Sheryl L Rifasshiman, Scott T Weiss, Diane R Gold, Augusto A LitonjuaAbstract:BACKGROUND: Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology. OBJECTIVE: To identify differences in plasma Metabolites between children with and without current asthma at mid-childhood. METHODS: We used untargeted mass spectrometry to measure plasma Metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual Metabolites that were differentially abundant by case-control status. We tested significant Metabolites for replication in 411 children from the VDAART clinical trial. RESULTS: There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several Metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a Metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a Pyrimidine Metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome Metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04). CONCLUSIONS AND CLINICAL RELEVANCE: Current asthma is nominally associated with altered levels of several Metabolites, including Metabolites in the nicotinamide pathway, and a bacterial Metabolite derived from the gut microbiome.
Diane R Gold - One of the best experts on this subject based on the ideXlab platform.
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plasma Metabolite profiles in children with current asthma
Clinical & Experimental Allergy, 2018Co-Authors: Rachel S Kelly, Joanne E Sordillo, Jessica Laskysu, Amber Dahlin, Wei Perng, Sheryl L Rifasshiman, Scott T Weiss, Diane R Gold, Augusto A LitonjuaAbstract:BACKGROUND: Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology. OBJECTIVE: To identify differences in plasma Metabolites between children with and without current asthma at mid-childhood. METHODS: We used untargeted mass spectrometry to measure plasma Metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual Metabolites that were differentially abundant by case-control status. We tested significant Metabolites for replication in 411 children from the VDAART clinical trial. RESULTS: There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several Metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a Metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a Pyrimidine Metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome Metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04). CONCLUSIONS AND CLINICAL RELEVANCE: Current asthma is nominally associated with altered levels of several Metabolites, including Metabolites in the nicotinamide pathway, and a bacterial Metabolite derived from the gut microbiome.
George C. Daher - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of Pyrimidine analogues and their nucleosides
Pharmacology & Therapeutics, 2002Co-Authors: George C. Daher, Barry E. Harris, Robert B. DiasioAbstract:Abstract The Pyrimidine antiMetabolite drugs consist of base and nucleoside analogues of the naturally occurring Pyrimidines uracil, thymine and cytosine. As is typical of antiMetabolites, these drugs have a strong structural similarity to endogenous nucleic acid precursors. The structural differences are usually substitutions at one of the carbons in the Pyrimidine ring itself or substitutions at one of the hydrogens attached to the ring of the Pyrimidine or sugar (ribose or deoxyribose). Despite the differences noted above, these analogues, can still be taken up into cells and then metabolized via anabolic or catabolic pathways used by endogenous Pyrimidines. Cytotoxicity results when the antiMetabolite either is incorporated in place of the naturally Pyrimidine Metabolite into a key molecule (such as RNA or DNA) or competes with the naturally occurring Pyrimidine Metabolite for a critical enzyme. There are four Pyrimidine antiMetabolites that are currently used extensively in clinical oncology. These include the fluoroPyrimidines, fluorouracil and fluorodeoxyuridine, and the cytosine analogues, cytosine arabinoside and azacytidine.
Rachel S Kelly - One of the best experts on this subject based on the ideXlab platform.
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plasma Metabolite profiles in children with current asthma
Clinical & Experimental Allergy, 2018Co-Authors: Rachel S Kelly, Joanne E Sordillo, Jessica Laskysu, Amber Dahlin, Wei Perng, Sheryl L Rifasshiman, Scott T Weiss, Diane R Gold, Augusto A LitonjuaAbstract:BACKGROUND: Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology. OBJECTIVE: To identify differences in plasma Metabolites between children with and without current asthma at mid-childhood. METHODS: We used untargeted mass spectrometry to measure plasma Metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual Metabolites that were differentially abundant by case-control status. We tested significant Metabolites for replication in 411 children from the VDAART clinical trial. RESULTS: There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several Metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a Metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a Pyrimidine Metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome Metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04). CONCLUSIONS AND CLINICAL RELEVANCE: Current asthma is nominally associated with altered levels of several Metabolites, including Metabolites in the nicotinamide pathway, and a bacterial Metabolite derived from the gut microbiome.
