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IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans
Pearce, Neil,Blair, Aaron,Vineis, Paolo,Ahrens, Wolfgang,Andersen, Aage,Anto, Josep M.,Armstrong, Bruce K.,Baccarelli, Andrea A.,Beland, Frederick A.,Berrington, Amy,Bertazzi, Pier Alberto,Birnbaum, L U.S. Dept. of Health, Education, and Welfare, Publ 2015 Environmental health perspectives Vol.123 No.6
<P>Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.</P><P>Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.</P><P>Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.</P><P>Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health.</P><P>Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP, Cardis E, Cherrie JW, Christiani DC, Cocco P, Coggon D, Comba P, Demers PA, Dement JM, Douwes J, Eisen EA, Engel LS, Fenske RA, Fleming LE, Fletcher T, Fontham E, Forastiere F, Frentzel-Beyme R, Fritschi L, Gerin M, Goldberg M, Grandjean P, Grimsrud TK, Gustavsson P, Haines A, Hartge P, Hansen J, Hauptmann M, Heederik D, Hemminki K, Hemon D, Hertz-Picciotto I, Hoppin JA, Huff J, Jarvholm B, Kang D, Karagas MR, Kjaerheim K, Kjuus H, Kogevinas M, Kriebel D, Kristensen P, Kromhout H, Laden F, Lebailly P, LeMasters G, Lubin JH, Lynch CF, Lynge E, ‘t Mannetje A, McMichael AJ, McLaughlin JR, Marrett L, Martuzzi M, Merchant JA, Merler E, Merletti F, Miller A, Mirer FE, Monson R, Nordby KC, Olshan AF, Parent ME, Perera FP, Perry MJ, Pesatori AC, Pirastu R, Porta M, Pukkala E, Rice C, Richardson DB, Ritter L, Ritz B, Ronckers CM, Rushton L, Rusiecki JA, Rusyn I, Samet JM, Sandler DP, de Sanjose S, Schernhammer E, Seniori Costantini A, Seixas N, Shy C, Siemiatycki J, Silverman DT, Simonato L, Smith AH, Smith MT, Spinelli JJ, Spitz MR, Stallones L, Stayner LT, Steenland K, Stenzel M, Stewart BW, Stewart PA, Symanski E, Terracini B, Tolbert PE, Vainio H, Vena J, Vermeulen R, Victora CG, Ward EM, Weinberg CR, Weisenburger D, Wesseling C, Weiderpass E, Zahm SH. 2015. IARC Monographs: 40 years of evaluating carcinogenic hazards to humans. Environ Health Perspect 123:507–514; http://dx.doi.org/10.1289/ehp.1409149</P>
Suh, Haeyoung,birnbaumer, Lutz 아주대학교 의과학연구소 1996 아주의학 Vol.1 No.1
Purified skeletal muscle 1,4-dihydropyridine (DHP) receptois are composed of five polypeptides termed α₁, β, γ, α₂, and 5. Among these, the α₁ subunit is known to be sufficient to function as a voltage-dependent Ca^(2+) channel and a DHP receptor. The α₁ alone exhibits very similar allosteric regulation of DHP binding to that found in skeletal muscle T-tubules. However, we previously showed that in the absence of Ca^(2+), DHP binding to α₁ alone at subsaturating concentrations was reduced, which could be restored by the (-) stereoisomer of a phenylalkylamine, D600. We hypothesized that this difference is due to lack of other regulatory subunits, specifically the β, γ and α₂δ components that copurify with α₁. In order to test our hypothesis, we coexpressed the α₁ subunit with non-α₁ components in mouse fiboblasts, L cells, and monkey kidney cells, COS.M6 in various combinations-and compared their DHP binding activity for the effect of (-)D600 in the absence of Ca^(2+). Coexpression of 13 with α₁ did not normalize the abnormal enhancing effect of (-)D600 on DHP binding. Coexpression of either γ or α₂δ, partially reduced the enhancing effect of (-)D600. Importantly, coexpression of all the components, that is, when the receptor was composed of α₁β γα₂δ, completely abrogated the abnormal effect of (-)D600. Thus, our data clearly demonstrate that all the component copurifying with α₁ are essential to constitute the functional DHP receptor.