The Experts below are selected from a list of 36 Experts worldwide ranked by ideXlab platform
Gerald W. Tannock - One of the best experts on this subject based on the ideXlab platform.
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The Bowel Microbiota Moderates Host Physiological Responses to Dietary Konjac
2020Co-Authors: Wayne Young, Blair Lawley, Don E. Otter, Gemma Henderson, Gerald W. TannockAbstract:8 Animal Abstract Diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology and microbiota biochemistry because the carbohydrates become substrates for bacterial growth and metabolism. Conventional or germ- free weanling rats were fed a control diet or diets containing 1.25, 2.5, or 5% konjac (KJ), a commonly used ingredient in Asian foods, for 28 d. In the absence of a bowel microbiota, 5% KJ elicited a significant increase in colonic goblet cell numbers and increased expression of mast cell protease genes and of genes that were overrepresented in the KEGG pathway ''Metabolism of xenobiotics by cytochrome P450'' relative to the control diet. In contrast, feeding 5% KJ caused few changes in mucosal gene expression in conventional rats. Analysis of the colonic microbiota of conventional rats fed KJ showed modest increases in the proportions of Actinobacteria and Bacteroidetes relative to rats fed the control diet, with a concomitant reduction in Firmicutes, which included a 50% reduction in Lactobacillus abundance. Colonic concentrations of short-chain fatty Acids and colonic crypt lengths were increased by feeding KJ. Goblet cell numbers were greater in conventional rats fed KJ relative to the control diet but were lower compared with germ-free animals. Serum Metabolite profiles were different in germ-free and conventional rats. Metabolites that differed in concentration included several phospholipids, a Bile Acid Metabolite, and an intermediate product of tryptophan metabolism. Overall, KJ in the diet was potentially damaging to the bowel mucosa and produced a protective response from the host. This response was reduced by the presence of the bowel microbiota, which therefore ameliorated potentially detrimental effects of dietary KJ. J. Nutr. doi: 10.3945/jn.113.174854.
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Bowel Microbiota Moderate Host Physiological Responses to Dietary Konjac in Weanling Rats
Journal of Nutrition, 2013Co-Authors: Wayne Young, Blair Lawley, Don E. Otter, Gemma Henderson, Gerald W. TannockAbstract:: Diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology and microbiota biochemistry because the carbohydrates become substrates for bacterial growth and metabolism. Conventional or germ-free weanling rats were fed a control diet or diets containing 1.25, 2.5, or 5% konjac (KJ), a commonly used ingredient in Asian foods, for 28 d. In the absence of bowel microbiota, 5% KJ elicited a significant increase in colonic goblet cell numbers and increased expression of mast cell protease genes and of genes that were overrepresented in the KEGG pathway "Metabolism of xenobiotics by cytochrome P450" relative to the control diet. In contrast, feeding 5% KJ caused few changes in mucosal gene expression in conventional rats. Analysis of the colonic microbiota of conventional rats fed KJ showed modest increases in the proportions of Actinobacteria and Bacteroidetes relative to rats fed the control diet, with a concomitant reduction in Firmicutes, which included a 50% reduction in Lactobacillus abundance. Colonic concentrations of short-chain fatty Acids and colonic crypt lengths were increased by feeding KJ. Goblet cell numbers were greater in conventional rats fed KJ relative to the control diet but were lower compared with germ-free animals. Serum Metabolite profiles were different in germ-free and conventional rats. Metabolites that differed in concentration included several phospholipids, a Bile Acid Metabolite, and an intermediate product of tryptophan metabolism. Overall, KJ in the diet was potentially damaging to the bowel mucosa and produced a protective response from the host. This response was reduced by the presence of the bowel microbiota, which therefore ameliorated potentially detrimental effects of dietary KJ.
J Goto - One of the best experts on this subject based on the ideXlab platform.
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Synthesis of 3α,7α,14α-Trihydroxy-5β-cholan-24-oic Acid: A Potential Primary Bile Acid in Vertebrates
Chemical & Pharmaceutical Bulletin, 2004Co-Authors: Genta Kakiyama, J Goto, Nariyasu Mano, Takashi Iida, Takaaki Goto, Toshio NambaraAbstract:: A method for the synthesis of 3alpha,7alpha,14alpha-trihydroxy-5beta-cholan-24-oic Acid which is a possible candidate of Bile Acid Metabolite in vertebrates was developed. The principal reactions involved were 1). stereoselective remote-hydroxylation of methyl ursodeoxycholate diacetate with dimethyldioxirane, 2). site-selective protection at C-3 by tert-butyldimethylsilylation of the resulting 3alpha,7alpha,14alpha-trihydroxy ester, 3). oxidation of the diol with pyridinium dichromate adsorbed on activated alumina, 4). stereoselective reduction of the 7-ketone with zinc borohydride, and 5). cleavage of the protecting group at C-3 with p-toluenesulfonic Acid. A facile elimination of the 14alpha-hydroxy group under an Acidic or neutral condition is also described. The synthetic reference compound is now available for comparison with unidentified biliary Bile Acids detected in vertebrate Bile.
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Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-Bile Acid Metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.
Journal of immunological methods, 2000Co-Authors: N. Kobayashi, Hiroshi Oiwa, K Kubota, Saburo Sakoda, J GotoAbstract:Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic Acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a Bile Acid Metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of alpha-type and two kinds of beta-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between alpha-type and beta-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.
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Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-Bile Acid Metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.
Journal of Immunological Methods, 2000Co-Authors: N. Kobayashi, Hiroshi Oiwa, K Kubota, Saburo Sakoda, J GotoAbstract:Abstract Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic Acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a Bile Acid Metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of α-type and two kinds of β-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between α-type and β-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.
Wayne Young - One of the best experts on this subject based on the ideXlab platform.
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The Bowel Microbiota Moderates Host Physiological Responses to Dietary Konjac
2020Co-Authors: Wayne Young, Blair Lawley, Don E. Otter, Gemma Henderson, Gerald W. TannockAbstract:8 Animal Abstract Diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology and microbiota biochemistry because the carbohydrates become substrates for bacterial growth and metabolism. Conventional or germ- free weanling rats were fed a control diet or diets containing 1.25, 2.5, or 5% konjac (KJ), a commonly used ingredient in Asian foods, for 28 d. In the absence of a bowel microbiota, 5% KJ elicited a significant increase in colonic goblet cell numbers and increased expression of mast cell protease genes and of genes that were overrepresented in the KEGG pathway ''Metabolism of xenobiotics by cytochrome P450'' relative to the control diet. In contrast, feeding 5% KJ caused few changes in mucosal gene expression in conventional rats. Analysis of the colonic microbiota of conventional rats fed KJ showed modest increases in the proportions of Actinobacteria and Bacteroidetes relative to rats fed the control diet, with a concomitant reduction in Firmicutes, which included a 50% reduction in Lactobacillus abundance. Colonic concentrations of short-chain fatty Acids and colonic crypt lengths were increased by feeding KJ. Goblet cell numbers were greater in conventional rats fed KJ relative to the control diet but were lower compared with germ-free animals. Serum Metabolite profiles were different in germ-free and conventional rats. Metabolites that differed in concentration included several phospholipids, a Bile Acid Metabolite, and an intermediate product of tryptophan metabolism. Overall, KJ in the diet was potentially damaging to the bowel mucosa and produced a protective response from the host. This response was reduced by the presence of the bowel microbiota, which therefore ameliorated potentially detrimental effects of dietary KJ. J. Nutr. doi: 10.3945/jn.113.174854.
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Bowel Microbiota Moderate Host Physiological Responses to Dietary Konjac in Weanling Rats
Journal of Nutrition, 2013Co-Authors: Wayne Young, Blair Lawley, Don E. Otter, Gemma Henderson, Gerald W. TannockAbstract:: Diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology and microbiota biochemistry because the carbohydrates become substrates for bacterial growth and metabolism. Conventional or germ-free weanling rats were fed a control diet or diets containing 1.25, 2.5, or 5% konjac (KJ), a commonly used ingredient in Asian foods, for 28 d. In the absence of bowel microbiota, 5% KJ elicited a significant increase in colonic goblet cell numbers and increased expression of mast cell protease genes and of genes that were overrepresented in the KEGG pathway "Metabolism of xenobiotics by cytochrome P450" relative to the control diet. In contrast, feeding 5% KJ caused few changes in mucosal gene expression in conventional rats. Analysis of the colonic microbiota of conventional rats fed KJ showed modest increases in the proportions of Actinobacteria and Bacteroidetes relative to rats fed the control diet, with a concomitant reduction in Firmicutes, which included a 50% reduction in Lactobacillus abundance. Colonic concentrations of short-chain fatty Acids and colonic crypt lengths were increased by feeding KJ. Goblet cell numbers were greater in conventional rats fed KJ relative to the control diet but were lower compared with germ-free animals. Serum Metabolite profiles were different in germ-free and conventional rats. Metabolites that differed in concentration included several phospholipids, a Bile Acid Metabolite, and an intermediate product of tryptophan metabolism. Overall, KJ in the diet was potentially damaging to the bowel mucosa and produced a protective response from the host. This response was reduced by the presence of the bowel microbiota, which therefore ameliorated potentially detrimental effects of dietary KJ.
Tommy B Andersson - One of the best experts on this subject based on the ideXlab platform.
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cyp3a specifically catalyzes 1β hydroxylation of deoxycholic Acid characterization and enzymatic synthesis of a potential novel urinary biomarker for cyp3a activity
Drug Metabolism and Disposition, 2016Co-Authors: Martin A Hayes, Xueqing Li, Gunnar Gronberg, Ulf Diczfalusy, Tommy B AnderssonAbstract:![Figure][1] The endogenous Bile Acid Metabolite 1 β -hydroxy-deoxycholic Acid (1 β -OH-DCA) excreted in human urine may be used as a sensitive CYP3A biomarker in drug development reflecting in vivo CYP3A activity. An efficient and stereospecific enzymatic synthesis of 1 β -OH-DCA was developed using a Bacillus megaterium (BM3) cytochrome P450 (P450) mutant, and its structure was confirmed by nuclear magnetic resonance (NMR) spectroscopy. A [2H4]-labeled analog of 1 β -OH-DCA was also prepared. The major hydroxylated Metabolite of deoxycholic Acid (DCA) in human liver microsomal incubations was identified as 1 β -OH-DCA by comparison with the synthesized reference analyzed by UPLC-HRMS. Its formation was strongly inhibited by CYP3A inhibitor ketoconazole. Screening of 21 recombinant human cytochrome P450 (P450) enzymes showed that, with the exception of extrahepatic CYP46A1, the most abundant liver P450 subfamily CYP3A, including CYP3A4, 3A5, and 3A7, specifically catalyzed 1 β -OH-DCA formation. This indicated that 1 β -hydroxylation of DCA may be a useful marker reaction for CYP3A activity in vitro. The metabolic pathways of DCA and 1 β -OH-DCA in human hepatocytes were predominantly via glycine and, to a lesser extent, via taurine and sulfate conjugation. The potential utility of 1 β -hydroxylation of DCA as a urinary CYP3A biomarker was illustrated by comparing the ratio of 1 β -OH-DCA:DCA in a pooled spot urine sample from six healthy control subjects to a sample from one patient treated with carbamazepine, a potent CYP3A inducer; 1 β -OH-DCA:DCA was considerably higher in the patient versus controls (ratio 2.8 vs. 0.4). Our results highlight the potential of 1 β -OH-DCA as a urinary biomarker in clinical CYP3A DDI studies. [1]: pending:yes
N. Kobayashi - One of the best experts on this subject based on the ideXlab platform.
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Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-Bile Acid Metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.
Journal of immunological methods, 2000Co-Authors: N. Kobayashi, Hiroshi Oiwa, K Kubota, Saburo Sakoda, J GotoAbstract:Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic Acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a Bile Acid Metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of alpha-type and two kinds of beta-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between alpha-type and beta-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.
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Monoclonal antibodies generated against an affinity-labeled immune complex of an anti-Bile Acid Metabolite antibody: an approach to noncompetitive hapten immunoassays based on anti-idiotype or anti-metatype antibodies.
Journal of Immunological Methods, 2000Co-Authors: N. Kobayashi, Hiroshi Oiwa, K Kubota, Saburo Sakoda, J GotoAbstract:Abstract Conventional immunoassays for haptens such as steroids and synthetic drugs are dependent on the competitive reaction between an unlabeled antigen (analyte) and a labeled antigen against a limited amount of anti-hapten antibody. Although noncompetitive immunoassay procedures such as two-site immunometric assays offer a much higher sensitivity, direct application of this principle to haptens has been difficult due to their small molecular mass precluding simultaneous binding by two antibody molecules. Here, we have attempted to develop a noncompetitive immunoassay system based on anti-idiotype or anti-metatype antibodies. Ursodeoxycholic Acid 7-N-acetylglucosaminide (UDCA 7-NAG), which is a Bile Acid Metabolite (molecular weight, 595.8), was selected as the model hapten. A/J mice were immunized with a monoclonal antibody against UDCA 7-NAG, which had been affinity-labeled with a relevant hapten derivative. The fusion between the immune spleen cells and P3/NS1/1-Ag4-1 myeloma cells yielded four kinds of α-type and two kinds of β-type monoclonal anti-idiotype antibodies, each recognizing the framework region and paratope of the anti-hapten antibody. The use of a selected combination between α-type and β-type antibodies together with the anti-hapten antibody provided a noncompetitive assay system with a subfemtomole order sensitivity (detection limit, 118 amol) and a practical specificity.
