An estrogen receptor （ER）/androgen receptor （AR） ligand competitive binding assay （ER/AR-binding assay） and chemical analyses were used to evaluate the endocrine disrupting chemicals （EDCs） behavior of two mun...An estrogen receptor （ER）/androgen receptor （AR） ligand competitive binding assay （ER/AR-binding assay） and chemical analyses were used to evaluate the endocrine disrupting chemicals （EDCs） behavior of two municipal wastewater treatment plants （WWTPs） （K and S）. In the influents, estrone （E 1）, androsterone （A）, androstenedione （AD）, BPA （bisphenol A）, NP （nonylphenol） and daidzein （DZ） were detected in high amounts with subsequent 24 h-average concentrations of 350, 1000, 29, 1300, 3900, and 5700 ng/L in K-WWTP and of 310, 620, 59, 1600, 2600, and 8400 ng/L in S-WWTP. The estrogenic （androgenic） activity as 17β-estradiol （E2） equivalents （EEQ） or testosterone （Te） equivalents （TEQ） was consequently 620 ng E2/L （570 ng Te/L） and 580 ng E2/L （800 ng Te/L） for the two WWTPs. The removal efficiencies of the above mentioned sole target chemicals were 51%-100% for K-WWTP and 55.6%-100% for S-WWTP. The removal efficiencies of EEQ were about 73% for both WWTPs, while the removal efficiencies of TEQ were 62.1% for K-WWTP and 98.4% for S-WWTP. In addition, chemical-derived EEQ were about 1.2%-52.4% of those by ER-binding assay for K-WWTP and the corresponding ratios were 1.3%-83.3% for S-WWTP, while chemical derived TEQ were less than 3% of values measured by the AR-binding assay for both WWTPs.展开更多
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are tr...Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed analysis.Administration of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of GVHD.Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO mice.Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO mice.Adoptive cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells.ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be evaluated.Therefore,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.展开更多
文摘An estrogen receptor （ER）/androgen receptor （AR） ligand competitive binding assay （ER/AR-binding assay） and chemical analyses were used to evaluate the endocrine disrupting chemicals （EDCs） behavior of two municipal wastewater treatment plants （WWTPs） （K and S）. In the influents, estrone （E 1）, androsterone （A）, androstenedione （AD）, BPA （bisphenol A）, NP （nonylphenol） and daidzein （DZ） were detected in high amounts with subsequent 24 h-average concentrations of 350, 1000, 29, 1300, 3900, and 5700 ng/L in K-WWTP and of 310, 620, 59, 1600, 2600, and 8400 ng/L in S-WWTP. The estrogenic （androgenic） activity as 17β-estradiol （E2） equivalents （EEQ） or testosterone （Te） equivalents （TEQ） was consequently 620 ng E2/L （570 ng Te/L） and 580 ng E2/L （800 ng Te/L） for the two WWTPs. The removal efficiencies of the above mentioned sole target chemicals were 51%-100% for K-WWTP and 55.6%-100% for S-WWTP. The removal efficiencies of EEQ were about 73% for both WWTPs, while the removal efficiencies of TEQ were 62.1% for K-WWTP and 98.4% for S-WWTP. In addition, chemical-derived EEQ were about 1.2%-52.4% of those by ER-binding assay for K-WWTP and the corresponding ratios were 1.3%-83.3% for S-WWTP, while chemical derived TEQ were less than 3% of values measured by the AR-binding assay for both WWTPs.
基金This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology(MEXT)of Japan(22220007,26221005 and 15K09783)the Project for Development of Innovative Research on Cancer Therapeutics(P-DIRECT)and the Project for Cancer Research And Therapeutic Evolution(P-CREATE)from Japan Agency for Medical Research and Development(AMED)+2 种基金a grant from Tokyo Biochemical Research Foundationa Keio University Grant-in-Aid for Encouragement of Young Medical Scientistsa Grant-in-Aid from the Keio Medical Association.
文摘Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed analysis.Administration of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of GVHD.Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO mice.Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO mice.Adoptive cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells.ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be evaluated.Therefore,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.
