FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Xie, YL Yang, JH Kwong, K AF Xie, Yili Yang, Jianhui Kwong, King TI Role of microRNA in XIAP expression in non-small cell lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Xie, Yili; Yang, Jianhui; Kwong, King] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2524 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803150 ER PT J AU Xie, YL Yang, JH Kwong, K AF Xie, Yili Yang, Jianhui Kwong, King TI Computational predictive modeling and heuristic analysis for identifying microRNA associated with XIAP in lung cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Xie, Yili; Yang, Jianhui; Kwong, King] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2464 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801061 ER PT J AU Xu, JM Heilpern, C Xu, H Kopelovich, L Athar, M AF Xu, Jianmin Heilpern, Clay Xu, Hui Kopelovich, Levy Athar, Mohammad TI CP-31398 inhibits growth of human rhabdomyosarcoma cells by activating p53-mitochondria-dependant apoptosis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 601 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701804398 ER PT J AU Xu, NZ Gill, R Demelash, A Meerzaman, D Jen, J Linnoila, I AF Xu Naizhen Gill, Rajbir Demelash, Abeba Meerzaman, Daoud Jen, Jin Linnoila, Ilona TI PGP9.5 contributes to neuroendocrine cell hyperplasia in post-naphthalene airway repair SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Xu Naizhen; Gill, Rajbir; Demelash, Abeba; Meerzaman, Daoud; Jen, Jin; Linnoila, Ilona] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2571 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803289 ER PT J AU Xu, XL Fang, YG Lee, T Forrest, D Jhanwar, S Abramson, D Cobrinik, D AF Xu, Xiaoliang Fang, Yugiang Lee, Thomas Forrest, Douglas Jhanwar, Suresh Abramson, David Cobrinik, David TI Cone precursor circuitry underlying retinoblastoma tumorigenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3128 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803418 ER PT J AU Yamashita, T Ji, JF Budhu, A Forgues, M Jia, HL Ye, QH Qin, LX Wauthier, E Reid, L Minato, H Honda, M Kaneko, S Yang, W Wang, HY Tang, ZY Wang, X AF Yamashita, Taro Ji, Junfang Budhu, Anuradha Forgues, Marshonna Jia, Huliang Ye, Qinghai Qin, Lun-Xiu Wauthier, Elaine Reid, Lola Minato, Hiroshi Honda, Masao Kaneko, Shuichi Yang, Wen Wang, Hongyang Tang, Zhao-You Wang, Xin TI Bolstering hepatic cancer stem cells by wnt/\#946;-catenin signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 Kanazawa Univ, Dept Gastroenterol, Sch Med, Kanazawa, Ishikawa, Japan. NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC USA. Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1948 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803403 ER PT J AU Yang, H Gonzalez-Bosquet, J Lacey, J Brinton, L Lissowska, J Peplonska, B Gaudet, M Sherman, M Chanock, S Garcia-Closas, M AF Yang, Hannah Gonzalez-Bosquet, Jesus Lacey, James Brinton, Louise Lissowska, Jolanta Peplonska, Beata Gaudet, Mia Sherman, Mark Chanock, Stephen Garcia-Closas, Montserrat TI Haplotype analyses of CYP19A1 and risk of endometrial cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Rockville, MD USA. M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Inst Oncol, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. NCI, Core Genotype Facil, Adv Technol Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3951 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703236 ER PT J AU Yang, JH Xie, YL Kwong, K AF Yang, Jianhui Xie, Yili Kwong, King TI Smac modulation of apoptosis induction in TRAIL-resistant non-small cell lung cancers SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Jianhui; Xie, Yili; Kwong, King] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5497 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705044 ER PT J AU Yang, JH Xie, YL Kwong, K AF Yang, Jianhui Xie, Yili Kwong, King TI Stable transfection of shRNA against XIAP attenuates intrinsic TRAIL resistance in non-small cell lung cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Jianhui; Xie, Yili; Kwong, King] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5535 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803234 ER PT J AU Yang, LX Tseng, Y Melillo, G Shih, SF Ou, CJ Chang, L Chen, YR Liu, JJ Liao, W Hong, K AF Yang, Li-Xi Tseng, Yunlong Melillo, Giovanni Shih, Sheue-Fang Ou, Ching-Ju Chang, Lo Chen, Yu-Ru Liu, Jun-Jen Liao, Wayne Hong, Keelung TI TLC388: A novel camptothecin derivative for improved cancer therapy SO CANCER RESEARCH LA English DT Meeting Abstract C1 Calif Pacific Med Ctr, San Francisco, CA USA. Taiwan Liposome Co LTD, Taipei, Taiwan. NCI, Tumor Hypoxia Lab Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21701 USA. Taipei Med Univ, Taipei, Taiwan. TLC Biopharmaceut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1703 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702704431 ER PT J AU Yang, XP Lu, H Yan, B Duggal, P Chuang, R Friedman, J Ehsanian, R Van Waes, C Chen, Z AF Yang, Xinping Lu, Hai Yan, Bin Duggal, Praveen Chuang, Ryan Friedman, Jay Ehsanian, Reza Van Waes, Carter Chen, Zhong TI \#916;Np63 modulates survival and inflammatory gene programs overlapping with the NF-\#954;\#914; transcriptome in head and neck cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Xinping; Lu, Hai; Yan, Bin; Duggal, Praveen; Chuang, Ryan; Friedman, Jay; Ehsanian, Reza; Van Waes, Carter; Chen, Zhong] NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4261 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701802230 ER PT J AU Yang, XY Popescu, N Zimonjic, D AF Yang, Xu-Yu Popescu, Nicholas Zimonjic, Drazen TI DLC1 tumor suppressor gene downregulates S100A10 expression and attenuates plasminogen to plasmin conversion SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yang, Xu-Yu; Popescu, Nicholas; Zimonjic, Drazen] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4349 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803433 ER PT J AU Yeung, C Ngo, V Wan, X Kim, SY Grohar, P Khanna, C Staudt, L Helman, L AF Yeung, Choh Ngo, Vu Wan, Xiao Kim, Su Young Grohar, Patrick Khanna, Chand Staudt, Louis Helman, Lee TI rhabdomyosarcoma uncovers CRKL: Biological assessment confirms a role in tumor progression in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yeung, Choh; Ngo, Vu; Wan, Xiao; Kim, Su Young; Grohar, Patrick; Khanna, Chand; Staudt, Louis; Helman, Lee] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5683 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702702213 ER PT J AU Yeung, C Ngo, V Wan, X Kim, SY Grohar, P Khanna, C Staudt, L Heiman, L AF Yeung, Choh Ngo, Vu Wan, Xiao Kim, Su Young Grohar, Patrick Khanna, Chand Staudt, Louis Heiman, Lee TI Loss of function screen in rhabdomyosarcoma uncovers CRKL: Biological assessment confirms a role in tumor progression in vitro and in vivo SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yeung, Choh; Ngo, Vu; Wan, Xiao; Kim, Su Young; Grohar, Patrick; Khanna, Chand; Staudt, Louis; Heiman, Lee] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 5683 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702804372 ER PT J AU Yin, YZ Pollock, C Tallapragada, S Yuan, HY Kopelovich, L Glazer, R AF Yin, Yuzhi Pollock, Claire Tallapragada, Sruthi Yuan, Hongyan Kopelovich, Levy Glazer, Robert TI Stem cell antigen-1 (Sca-1) supports proliferation and tumor growth through PI3K, PDK1 and PPAR\#948; signaling SO CANCER RESEARCH LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 1945 PG 1 WC Oncology SC Oncology GA V43TD UT WOS:000209702803400 ER PT J AU Yong, L Peterson, M Sigurdson, A Sampson, L Ward, E AF Yong, Lee Peterson, Martin Sigurdson, Alice Sampson, Laura Ward, Elizabeth TI Antioxidant intake and chromosome translocation frequency among airline pilots SO CANCER RESEARCH LA English DT Meeting Abstract C1 NIOSH, CDC, Cincinnati, OH 45226 USA. NCI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Amer Canc Soc, Atlanta, GA 30329 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 73 PG 1 WC Oncology SC Oncology GA V43TC UT WOS:000209702705016 ER PT J AU Zabirnyk, O Liu, W Phang, J AF Zabirnyk, Olga Liu, Wei Phang, James TI Oxidized low-density lipoproteins and its constituent 7-ketocholesterol regulate a stress-response mechanism through PPAR\#947; in cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zabirnyk, Olga; Liu, Wei; Phang, James] NCI, Comparat Carcinogenesis Lab, CCR, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 3420 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701803051 ER PT J AU Zanetti, K Welsh, J Bowman, E Goodman, J Bernig, T Chanock, S Harris, C AF Zanetti, Krista Welsh, Judith Bowman, Elise Goodman, Julie Bernig, Toralf Chanock, Stephen Harris, Curtis TI MBL2 secretor haplotypes are associated with increased colon cancer susceptibility in African Americans SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Gradient Corp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2117 PG 2 WC Oncology SC Oncology GA V43TC UT WOS:000209702703194 ER PT J AU Zhang, JH Greenblum, S Clifford, R Hu, Y Monks, A Hose, C Collins, J Wu, XL Doroshow, J Buetow, K AF Zhang, Jinghui Greenblum, Sharon Clifford, Robert Hu, Ying Monks, Anne Hose, Curtis Collins, Jerry Wu, Xiaolin Doroshow, James Buetow, Kenneth TI Doxorubicin induces activation of p53 pathway in sensitive NCI-60 cell lines that have the composite genotype of wild-type p53and mutant p16 SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Rockville, MD USA. SAIC Frederick Inc, NCI Frederick, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2424 PG 1 WC Oncology SC Oncology GA V43ST UT WOS:000209701801018 ER PT J AU Zhang, YW Jones, T Martin, S Caplen, N Pommier, Y AF Zhang, Yongwei Jones, Tamara Martin, Scott Caplen, Natasha Pommier, Yves TI Implication of ATM-/ATR-Chk1-E2F1-dependent up-regulation of ribonucleotide reductase R2 (RRM2) in DNA damage response SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Zhang, Yongwei; Jones, Tamara; Martin, Scott; Caplen, Natasha; Pommier, Yves] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 4664 PG 2 WC Oncology SC Oncology GA V43TB UT WOS:000209702604206 ER PT J AU Zhou, HZ Bennett, E Diaw, L Moore, H Robb, J Ohgi, S De Rozieres, S Muller, R Vaught, J Compton, C Gillespie, J AF Zhou, Huizhi Bennett, Ellie Diaw, Lena Moore, Helen Robb, Jim Ohgi, Sharron De Rozieres, Sohela Muller, Rolf Vaught, Jim Compton, Carolyn Gillespie, John TI Efficacy of RNase inhibitors and two nucleic acid preservatives to preserve RNA in colon cancer tissue sections for laser capture microdissection SO CANCER RESEARCH LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. Biomatrica Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2009 VL 69 SU 9 MA 2610 PG 2 WC Oncology SC Oncology GA V43ST UT WOS:000209701805171 ER PT J AU Tsoumpou, I Arbyn, M Kyrgiou, M Wentzensen, N Koliopoulos, G Martin-Hirsch, P Malamou-Mitsi, V Paraskevaidis, E AF Tsoumpou, I. Arbyn, M. Kyrgiou, M. Wentzensen, N. Koliopoulos, G. Martin-Hirsch, P. Malamou-Mitsi, V. Paraskevaidis, E. TI p16(INK4a) immunostaining in cytological and histological specimens from the uterine cervix: A systematic review and meta-analysis SO CANCER TREATMENT REVIEWS LA English DT Review DE Cancer; Dysplasia; SIL; CIN; Cervix; p16; Cyclin-dependent kinase ID LIQUID-BASED CYTOLOGY; HUMAN-PAPILLOMAVIRUS INFECTION; HIGH-RISK HPV; SQUAMOUS INTRAEPITHELIAL LESIONS; IN-SITU HYBRIDIZATION; IMMUNOHISTOCHEMICAL P16 EXPRESSION; ENDOCERVICAL GLANDULAR LESIONS; EQUIVOCAL PAP-SMEARS; FOLLOW-UP; DNA DETECTION AB Background: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment. Material and methods: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion. Results: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%)and 82% of CIN3 (95% CI: 72-92%). Conclusion: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Tsoumpou, I.] CMMC Univ Hosp, St Marys Hosp, Dept Obstet & Gynaecol, Manchester M13 0JH, Lancs, England. [Arbyn, M.] Sci Inst Publ Hlth, B-1050 Brussels, Belgium. [Kyrgiou, M.] W Middlesex Univ Hosp, Dept Obstet & Gynaecol, London, England. [Wentzensen, N.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. [Koliopoulos, G.; Paraskevaidis, E.] Univ Ioannina, Sch Med, Dept Obstet & Gynaecol, GR-45110 Ioannina, Greece. [Martin-Hirsch, P.] Cent Lancashire Teaching Hosp, Dept Obstet & Gynaecol, Preston, Lancs, England. [Malamou-Mitsi, V.] Univ Ioannina, Sch Med, Dept Pathol, GR-45110 Ioannina, Greece. RP Tsoumpou, I (reprint author), CMMC Univ Hosp, St Marys Hosp, Dept Obstet & Gynaecol, Manchester M13 0JH, Lancs, England. EM ioantsoumpou@hotmail.com RI Arbyn, Marc/B-6887-2009 FU Gynaecological Cancer Cochrane Review Collaboration (Bath, United Kingdom); European Commission FX Marc Arbyn received funding from the Gynaecological Cancer Cochrane Review Collaboration (Bath, United Kingdom) and the European Commission (Directorate of SANCO, Luxembourg, Grand-Duchy of Luxembourg) through the ECCG (European Cooperation on development and implementation of Cancer screening and prevention Guidelines, IARC, Lyon, France). NR 114 TC 152 Z9 167 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD MAY PY 2009 VL 35 IS 3 BP 210 EP 220 DI 10.1016/j.ctrv.2008.10.005 PG 11 WC Oncology SC Oncology GA 447JU UT WOS:000266188200003 PM 19261387 ER PT J AU Ahn, J Albanes, D Berndt, SI Peters, U Chatterjee, N Freedman, ND Abnet, CC Huang, WY Kibel, AS Crawford, ED Weinstein, SJ Chanock, SJ Schatzkin, A Hayes, RB AF Ahn, Jiyoung Albanes, Demetrius Berndt, Sonja I. Peters, Ulrike Chatterjee, Nilanjan Freedman, Neal D. Abnet, Christian C. Huang, Wen-Yi Kibel, Adam S. Crawford, E. David Weinstein, Stephanie J. Chanock, Stephen J. Schatzkin, Arthur Hayes, Richard B. CA Prostate Lung Colorectal Ovarian T TI Vitamin D-related genes, serum vitamin D concentrations and prostate cancer risk SO CARCINOGENESIS LA English DT Article ID D-RECEPTOR GENE; 1,25-DIHYDROXYVITAMIN D-3; MESSENGER-RNA; SUBSEQUENT DEVELOPMENT; SIGNALING PATHWAYS; UNITED-STATES; D METABOLITES; POLYMORPHISMS; 25-HYDROXYVITAMIN-D; ASSOCIATION AB We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 25(OH)D (all cases and controls) and 1,25(OH)(2)D (a subset of 150 controls) levels were measured by radioimmunoassay and SNP data were genotyped as part of a genome-wide scan. Among investigated SNPS, only four tag SNPS in GC, the major serum 25(OH)D carrier, were associated with 25(OH)D levels; no SNPS were associated with 1,25(OH)(2)D levels. None of the 212 SNPS examined were associated with cancer risk overall. Among men in the lowest tertile of serum 25(OH)D (< 48.9 nmol/l), however, prostate cancer risk was related to tag SNPS in or near the 3' untranslated region (UTR) of VDR, with the strongest association for rs11574143 [odds ratio (95% confidence interval) for risk allele carriers versus wild-type: 2.49 (1.51-4.11), P = 0.0007]; the genotype associations were null among men in tertile 2 and tertile 3. Results from the most comprehensive evaluation of serum vitamin D and its related genes to date suggest that tag SNPS in the 3' UTR of VDR may be associated with risk of prostate cancer in men with low vitamin D status. C1 [Ahn, Jiyoung; Albanes, Demetrius; Berndt, Sonja I.; Chatterjee, Nilanjan; Freedman, Neal D.; Abnet, Christian C.; Huang, Wen-Yi; Weinstein, Stephanie J.; Chanock, Stephen J.; Schatzkin, Arthur; Prostate Lung Colorectal Ovarian T] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Peters, Ulrike] Univ Washington, Canc Prevent Program, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98109 USA. [Kibel, Adam S.] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. [Crawford, E. David] Anschutz Canc Pavil Univ Colorado, Aurora, CO 80014 USA. RP Ahn, J (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ahnj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Hayes, Richard/0000-0002-0918-661X FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health; Division of Cancer Prevention; Department of Human and Human Services FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Human and Human Services. NR 42 TC 88 Z9 90 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2009 VL 30 IS 5 BP 769 EP 776 DI 10.1093/carcin/bgp055 PG 8 WC Oncology SC Oncology GA 441AB UT WOS:000265740000008 PM 19255064 ER PT J AU Li, YL Ambrosone, CB McCullough, MJ Ahn, J Stevens, VL Thun, MJ Hong, CC AF Li, Yulin Ambrosone, Christine B. McCullough, Marjorie J. Ahn, Jiyoung Stevens, Victoria L. Thun, Michael J. Hong, Chi-Chen TI Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk SO CARCINOGENESIS LA English DT Article ID NITRIC-OXIDE SYNTHASE; HEME OXYGENASE-1 GENE; MICROSATELLITE POLYMORPHISM; PROMOTER POLYMORPHISM; MYELOPEROXIDASE GENE; TUMOR PROGRESSION; REDOX REGULATION; REACTIVE OXYGEN; LUNG; CELLS AB Dietary antioxidants may interact with endogenous sources of pro- and antioxidants to impact breast cancer risk. A nested case-control study of postmenopausal women (505 cases and 502 controls) from the Cancer Prevention Study-II Nutrition Cohort was conducted to examine the interaction between oxidative stress-related genes and level of vegetable and fruit intake on breast cancer risk. Genetic variations in catalase (CAT) (C-262T), myeloperoxidase (MPO) (G-463A), endothelial nitric oxide synthase (NOS3) (G894T) and heme oxygenase-1 (HO-1) [(GT)(n) dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low-risk CAT CC [odds ratio (OR) = 0.75, 95% confidence interval (CI) 0.50-1.11], NOS3 TT (OR = 0.54, 95% CI = 0.26-1.12, P-trend = 0.10) or HO-1 S allele and MM genotype (OR = 0.56, 95% CI = 0.37-0.55), however, were found to be at non-significantly reduced breast cancer risk among those with high vegetable and fruit intake (>= median; P-interactions = 0.04 for CAT, P = 0.005 for NOS3 and P = 0.07 for HO-1). Furthermore, those with >= 4 putative low-risk alleles in total had significantly reduced risk (OR = 0.53, 95% CI = 0.32-0.88, P-interaction = 0.006) compared with those with <= 2 low-risk alleles. In contrast, among women with low vegetable and fruit intake (< median), the low-risk CAT CC (OR = 1.33, 95% CI = 0.89-1.99), NOS3 TT (OR = 2.93, 95% CI = 1.38-6.22) and MPO AA (OR = 2.09, 95% CI = 0.73-5.95) genotypes appeared to be associated with raised breast cancer risk, with significantly increased risks observed in those with >= 4 low-risk alleles compared with participants with <= 2 low-risk alleles (OR = 1.77, 95% CI = 1.05-2.99, P-interaction = 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants. C1 [Li, Yulin; Ambrosone, Christine B.; Hong, Chi-Chen] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [McCullough, Marjorie J.; Stevens, Victoria L.; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Ahn, Jiyoung] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hong, CC (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent & Control, Elm & Carlton St, Buffalo, NY 14263 USA. EM Chi-Chen.Hong@RoswellPark.org NR 84 TC 43 Z9 46 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2009 VL 30 IS 5 BP 777 EP 784 DI 10.1093/carcin/bgp053 PG 8 WC Oncology SC Oncology GA 441AB UT WOS:000265740000009 PM 19255063 ER PT J AU Staiger, J Lueben, MJ Berrigan, D Malik, R Perkins, SN Hursting, SD Johnson, PF AF Staiger, Jennifer Lueben, Mary J. Berrigan, David Malik, Radek Perkins, Susan N. Hursting, Stephen D. Johnson, Peter F. TI C/EBP beta regulates body composition, energy balance-related hormones and tumor growth SO CARCINOGENESIS LA English DT Article ID BINDING-PROTEIN-DELTA; FACTOR-I GENE; OSTEOBLAST-ENRICHED CULTURES; FETAL-RAT BONE; CALORIE RESTRICTION; ADIPOCYTE DIFFERENTIATION; LEPTIN CONCENTRATIONS; SKIN TUMORIGENESIS; CANCER PREVENTION; SEXUAL-DIMORPHISM AB The prevalence of obesity, an established epidemiologic risk factor for many chronic diseases including cancer, has been steadily increasing in the US over several decades. The mechanisms used to regulate energy balance and adiposity and the relationship of these factors to cancer are not completely understood. Here we have used knockout mice to examine the roles of the transcription factors CCAAT/enhancer-binding protein (C/EBP) beta and C/EBP delta in regulating body composition and systemic levels of hormones such as insulin-like growth factor-1 (IGF-1), leptin and insulin that mediate energy balance. Dual-energy X-ray absorptiometry showed that C/EBP beta, either directly or indirectly, modulated body weight, fat content and bone density in both males and females, while the effect of C/EBP delta was minor and only affected adiposity and body weight in female animals. Levels of IGF-1, leptin and insulin in the serum were decreased in both male and female C/EBP beta(-/-) mice, and C/EBP beta was associated with their promoters in vivo. Moreover, colon adenocarcinoma cells displayed reduced tumorigenic potential when transplanted into C/EBP beta-deficient animals, especially males. Thus, C/EBP beta contributes to endocrine expression of IGF-1, leptin and insulin, which modulate energy balance and can contribute to cancer progression by creating a favorable environment for tumor cell proliferation and survival. C1 [Staiger, Jennifer; Lueben, Mary J.; Malik, Radek; Johnson, Peter F.] Natl Canc Inst Frederick, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA. [Staiger, Jennifer; Lueben, Mary J.] Mt St Marys Univ, Dept Sci, Emmitsburg, MD 21727 USA. [Berrigan, David] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Perkins, Susan N.; Hursting, Stephen D.] Univ Texas Austin, Dept Human Ecol, Austin, TX 78712 USA. RP Johnson, PF (reprint author), Natl Canc Inst Frederick, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012; Malik, Radek/G-3578-2014 OI Johnson, Peter/0000-0002-4145-4725; FU Intramural Research Program of the National Institutes of Health; National Cancer Institute, Center for Cancer Research FX Intramural Research Program of the National Institutes of Health; National Cancer Institute, Center for Cancer Research. NR 82 TC 18 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 2009 VL 30 IS 5 BP 832 EP 840 DI 10.1093/carcin/bgn273 PG 9 WC Oncology SC Oncology GA 441AB UT WOS:000265740000016 PM 19056928 ER PT J AU Memmott, RM Dennis, PA AF Memmott, Regan M. Dennis, Phillip A. TI Akt-dependent and -independent mechanisms of mTOR regulation in cancer SO CELLULAR SIGNALLING LA English DT Review DE mTOR; Cancer; Akt; AMPK ID ACTIVATED PROTEIN-KINASE; TUBEROUS SCLEROSIS COMPLEX; INTEGRIN-LINKED KINASE; ETHER LIPID ANALOGS; TUMOR-CELL-GROWTH; MAMMALIAN TARGET; PHOSPHOLIPASE-D; BREAST-CANCER; LUNG-CANCER; IN-VIVO AB The protein kinase mTOR (mammalian target of rapamycin) is a critical regulator of cellular metabolism, growth, and proliferation. These processes contribute to tumor formation, and many cancers are characterized by aberrant activation of mTOR. Although activating mutations in mTOR itself have not been identified, deregulation of upstream components that regulate mTOR are prevalent in cancer. The prototypic mechanism of mTOR regulation in cells is through activation of the PI3K/Akt pathway, but mTOR receives input from multiple signaling pathways. This review will discuss Akt-dependent and -independent mechanisms of mTOR regulation in response to mitogenic signals, as well as its regulation in response to energy and nutrient-sensing pathways. Preclinical and clinical studies have demonstrated that tumors bearing genetic alterations that activate mTOR are sensitive to pharmacologic inhibition of mTOR. Elucidation of novel pathways that regulate mTOR may help identify predictive factors for sensitivity to mTOR inhibitors, and could provide new therapeutic targets for inhibiting the mTOR pathway in cancer. This review will also highlight pharmacologic approaches that inhibit mTOR via activation of the AMP-activated protein kinase (AMPK), an important inhibitor of the mTOR pathway and an emerging target in cancer. Published by Elsevier Inc. C1 [Memmott, Regan M.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 118 TC 172 Z9 185 U1 2 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAY PY 2009 VL 21 IS 5 BP 656 EP 664 DI 10.1016/j.cellsig.2009.01.004 PG 9 WC Cell Biology SC Cell Biology GA 423UN UT WOS:000264521300002 PM 19166931 ER PT J AU Omar, B Zmuda-Trzebiatowska, E Manganiello, V Goransson, O Degerman, E AF Omar, Bilal Zmuda-Trzebiatowska, Emilia Manganiello, Vincent Goransson, Olga Degerman, Eva TI Regulation of AMP-activated protein kinase by cAMP in adipocytes: Roles for phosphodiesterases, protein kinase B, protein kinase A, Epac and lipolysis SO CELLULAR SIGNALLING LA English DT Article DE PDE3B; PDE4; Epac; AMPK; PKA; Lipolysis; cAMP; Adipocytes ID INSULIN-INDUCED PHOSPHORYLATION; CYCLIC-AMP; RAT ADIPOCYTES; FATTY-ACIDS; BETA; 3B; MECHANISM; UPSTREAM; ISCHEMIA; TARGET AB AMP-activated protein kinase (AMPK) is an important regulator of cellular energy status. In adipocytes, stimuli that increase intracellular cyclic AMP (cAMP) have also been shown to increase the activity of AMPK. The precise molecular mechanisms responsible for cAMP-induced AMPK activation are not clear. Phosphodiesterase 3B (PDE3B) is a critical regulator of cAMP signaling in adipocytes. Here we investigated the roles of PDE3B, PDE4, protein kinase B (PKB) and the exchange protein activated by cAMP 1 (Epac1), as well as lipolysis, in the regulation of AMPK in primary rat adipocytes. We demonstrate that the increase in phosphorylation of AMPK at T172 induced by the adrenergic agonist isoproterenol can be diminished by co-incubation with insulin. The diminishing effect of insulin on AMPK activation was reversed upon treatment with the PDE3B specific inhibitor OPC3911 but not with the PDE4 inhibitor Rolipram. Adenovirus-mediated overexpression of PDE3B and constitutively active PKB both resulted in greatly reduced isoproterenol-induced phosphorylation of AMPK at T172. Co-incubation of adipocytes with isoproterenol and the PKA inhibitor H89 resulted in a total ablation of lipolysis and a reduction in AMPK phosphorylation/activation. Stimulation of adipocytes with the Epac1 agonist 8-pCPT-2'O-Me-cAMP led to increased phosphorylation of AMPK at T172. The general lipase inhibitor Orlistat decreased isoproterenol-induced phosphorylation of AMPK at T172. This decrease corresponded to a reduction of lipolysis from adipocytes. Taken together, these data suggest that PDE3B and PDE4 regulate cAMP pools that affect the activation/phosphorylation state of AMPK and that the effects of cyclic AMP on AMPK involve Epac1, PKA and lipolysis. (C) 2009 Elsevier Inc. All rights reserved. C1 [Omar, Bilal; Zmuda-Trzebiatowska, Emilia; Goransson, Olga; Degerman, Eva] Lund Univ, Biomed Ctr, Dept Expt Med Sci C11, S-22184 Lund, Sweden. [Zmuda-Trzebiatowska, Emilia; Manganiello, Vincent] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Omar, B (reprint author), Lund Univ, Biomed Ctr, Dept Expt Med Sci C11, S-22184 Lund, Sweden. EM bilal.omar@med.lu.se FU Swedish Research Council [3362]; Lund University Diabetes Center.; Swedish Diabetes Association; Novo Nordisk, Denmark; Swedish Society of Medicine FX The authors would like to acknowledge Dr. Lena Stenson for the advice on the manuscript and Eva Ohlson for the excellent technical assistance. Bilal Omar is a recipient of a postdoctoral fellowship from the Tage Blucher foundation. This work was supported by the Swedish Research Council project 3362 and by the Lund University Diabetes Center. Grants were obtained from the following foundations: Swedish Diabetes Association; Novo Nordisk, Denmark, the Swedish Society of Medicine, Dr. R Hakansson and Albert PAhlsson. NR 34 TC 60 Z9 61 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAY PY 2009 VL 21 IS 5 BP 760 EP 766 DI 10.1016/j.cellsig.2009.01.015 PG 7 WC Cell Biology SC Cell Biology GA 423UN UT WOS:000264521300014 PM 19167487 ER PT J AU Pan, J Keffer, J Emami, A Ma, XY Lan, R Goldman, R Chung, FL AF Pan, Jishen Keffer, Jessica Emami, Armaghan Ma, Xiaoyue Lan, Renny Goldman, Radoslav Chung, Fung-Lung TI Acrolein-Derived DNA Adduct Formation in Human Colon Cancer Cells: Its Role in Apoptosis Induction by Docosahexaenoic Acid SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; NUCLEOTIDE EXCISION-REPAIR; DEOXYGUANOSINE ADDUCTS; LIPID-PEROXIDATION; 1,N-2-PROPANODEOXYGUANOSINE ADDUCTS; TRANSLESION SYNTHESIS; MOLECULAR-MECHANISMS; COLORECTAL-CANCER; MISMATCH REPAIR; POLYMERASE-ETA AB The apoptotic effects of docosahexaenoic acid (DHA) and other omega-3 polyunsaturated fatty acids (PUFAs) have been documented in cell and animal studies. The molecular mechanism by which DHA induces apoptosis is unclear. Although there is no direct evidence, some studies have suggested that DNA damage generated through lipid peroxidation may be involved. Our previous studies showed that DHA, because it has a high degree of unsaturation, can give rise to the acrolein-derived 1,N(2)-propanodeoxyguanosine (Acr-dG) as a major class of DNA adducts via lipid oxidation. As a first step to investigate the possible role of oxidative DNA damage in apoptosis induced by DHA, we examined the relationships between oxidative DNA damage and apoptosis caused by DHA in human colon cancer HT-29 cells. Apoptosis and oxidative DNA damage, including Acr-dG and 8-oxo-deoxyguanosine (8-oxo-dG) formation, in cells treated with DHA and omega-6 PUFAs, including arachidonic acid (AA) and linoleic acid (LA), were measured. DHA induced apoptosis in a dose- and time-dependent manner with a concentration range from 0 to 300 mu M as indicated by increased caspase-3 activity and PARP cleavage. In contrast, AA and LA had little or no effect at these concentrations. The Acr-dG levels were increased in HT-29 cells treated with DHA at 240 and 300 mu M, and the increases were correlated with the induction of apoptosis at these concentrations, while no significant changes were observed for 8-oxo-dG. Because proteins may compete with DNA to react with acrolein, we then examined the effects of BSA on DHA-induced apoptosis and oxidative DNA damage. The addition of BSA to HT-29 cell culture media significantly decreases Acr-dG levels with a concomitant decrease in the apoptosis induced by DHA. The reduced Acr-dG formation is attributed to the reaction of BSA with acrolein as indicated by increased levels of total protein carbonyls. Similar correlations between Acr-dG formation and apoptosis were observed in HT-29 cells directly incubated with 0-200 mu M acrolein. Additionally, DHA treatment increased the level of DNA strand breaks and caused cell cycle arrested at G1 phase. Taken together, these results demonstrate the parallel relationships between Acr-dG level and apoptosis in HT-29 cells, suggesting that the formation of Acr-dG in cellular DNA may contribute to apoptosis induced by DHA. C1 [Pan, Jishen; Keffer, Jessica; Emami, Armaghan; Ma, Xiaoyue; Lan, Renny; Goldman, Radoslav; Chung, Fung-Lung] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Keffer, Jessica] NIDDK, NIH, Bethesda, MD 20892 USA. RP Chung, FL (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20057 USA. EM flc6@georgetown.edu OI Keffer, Jessica/0000-0002-0302-3588 FU NCI [CA043159, CA115625-01A2]; Flight Attendant Medical Research Institute [052444] FX We thank Dr. Karen Creswell and Michefle Lombard for conducting the flowcytometry experiments. This work was supported by NCI Grant CA043159 to F.-L.C. and in part by NCI Grant CA115625-01A2 and Flight Attendant Medical Research Institute award 052444 to R.G. NR 58 TC 25 Z9 25 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY PY 2009 VL 22 IS 5 BP 798 EP 806 DI 10.1021/tx800355k PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 447OQ UT WOS:000266201200007 PM 19341237 ER PT J AU Glasgow, CG Avila, NA Lin, JP Stylianou, MP Moss, J AF Glasgow, Connie G. Avila, Nilo A. Lin, Jing-Ping Stylianou, Mario P. Moss, Joel TI Serum Vascular Endothelial Growth Factor-D Levels in Patients With Lymphangioleiomyomatosis Reflect Lymphatic Involvement SO CHEST LA English DT Article DE adenopathy; angiomyolipoma; cystic lung disease; lymphangioleiomyoma; lymphatics; tuberous sclerosis complex; vascular endothelial growth factor-D ID TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; TSC2; WOMEN; LAM; LYMPHANGIOMYOMATOSIS; LYMPHANGIOGENESIS; TRANSPLANTATION; MUTATIONS; MECHANISM AB Background: Lymphangioleiomyomatosis (LAM) is a rare multisystem disorder affecting primarily women of child-bearing age, and characterized by cystic lung destruction, tumors of the kidney (angiomyolipomas [AMLs% and involvement of the axial lymphatics (lymphangioleiomyomas). Patients with LAM experience loss of pulmonary function attributed to the proliferation of abnormal-appearing smooth muscle-like cells (LAM cells). it is possible to group the LAM population by the presence or absence of extrapulmonary involvement (eg, AMLs, lymphangioleiomyomas, chylous effusions). Serum vascular endothelial growth factor (VEGF)-D, a lymphangiogenic factor, is higher in LAM patients than in healthy volunteers and has been proposed as a tool in the differential diagnosis of cystic lung disease. We assessed serum VEGF-D concentrations in relationship to clinical phenotype in LAM patients. Methods: Serum VEGF-D levels were quantified by enzyme immunosorbent assay for 111 patients with LAM and 40 healthy volunteers. VEGF-D levels in patients with pulmonary LAM, with or without extrapulmonary manifestations, were compared to those of healthy volunteers. Results: Serum VEGF-D levels were greater in patients with LAM compared to those of healthy volunteers (p < 0.001). However, when patient samples were grouped based on the extent of lymphatic extrapulmonary involvement (eg, lytnpbaingioleiomyomas and adenopathy), the statistical difference was maintained only for patients with LAM with lymphatic involvement (p < 0.001), not for those patients whose disease was restricted to the lung. Serum VEGF-D levels are a good biomarker for lymphatic involvement (area under the curve [AUC], 0.845; p < 0.0001), and a fair predictor for LAM disease (AUC, 0.7.51; p < 0.0001). Serum levels correlated to CT scan grade (p = 0.033). Conclusions: Serum VEGF-D concentration is a measure of lymphatic involvement in patients with LAM. (CHEST 2009; 135.1293-1300) C1 [Moss, Joel] NHLBI, Translat Med Branch, NIH, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Lin, Jing-Ping; Stylianou, Mario P.] NHLBI, Off Biostat Res, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Avila, Nilo A.] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Translat Med Branch, NIH, Div Prevent & Populat Sci, Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov FU Intramural NIH HHS NR 23 TC 50 Z9 51 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2009 VL 135 IS 5 BP 1293 EP 1300 DI 10.1378/chest.08-1160 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 442YF UT WOS:000265876100026 PM 19420197 ER PT J AU Meaburn, KJ Gudla, PR Khan, S Nandy, K Lockett, SJ Misteli, T AF Meaburn, Karen J. Gudla, Prabhakar R. Khan, Sameena Nandy, Kaustav Lockett, Stephen J. Misteli, Tom TI Breast cancer diagnostics based on interphase spatial genome positioning SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 17th International Chromosome Conference (ICC) CY JUN 23-26, 2009 CL Boone, NC C1 [Meaburn, Karen J.; Khan, Sameena; Misteli, Tom] NCI, NIH, Cell Biol Genomes Grp, Bethesda, MD 20892 USA. [Gudla, Prabhakar R.; Nandy, Kaustav; Lockett, Stephen J.] NCI, Adv Technol Program, Opt Microscopy & Anal Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2009 VL 17 IS 4 BP 536 EP 536 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 484OI UT WOS:000269055300018 ER PT J AU Nisha, P Lei, EP AF Nisha, Parul Lei, Elissa P. TI Differential effects of RNA silencing on the activities of two chromatin insulators SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 17th International Chromosome Conference (ICC) CY JUN 23-26, 2009 CL Boone, NC C1 [Nisha, Parul; Lei, Elissa P.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2009 VL 17 IS 4 BP 539 EP 539 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 484OI UT WOS:000269055300025 ER PT J AU Ebersole, TA Larionov, V AF Ebersole, Thomas A. Larionov, Vladimir TI Chromosomal domain assembly, conflict, and resolution in transgenesis SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 17th International Chromosome Conference (ICC) CY JUN 23-26, 2009 CL Boone, NC C1 [Ebersole, Thomas A.; Larionov, Vladimir] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2009 VL 17 IS 4 BP 547 EP 548 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 484OI UT WOS:000269055300046 ER PT J AU Longo, MS Carone, DM Green, ED O'Neill, MJ O'Neill, RJ AF Longo, Mark S. Carone, Dawn M. Green, Eric D. O'Neill, Michael J. O'Neill, Rachel J. TI Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 17th International Chromosome Conference (ICC) CY JUN 23-26, 2009 CL Boone, NC C1 [Longo, Mark S.; Carone, Dawn M.; O'Neill, Michael J.; O'Neill, Rachel J.] Univ Connecticut, Dept Mol & Cell Biol, Ctr Appl Genet & Technol, Storrs, CT 06269 USA. [Green, Eric D.] Genome Technol Branch, Bethesda, MD 20892 USA. [Green, Eric D.] NHGRI, NISC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD MAY PY 2009 VL 17 IS 4 BP 573 EP 573 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 484OI UT WOS:000269055300105 ER PT J AU Einhorn, PT AF Einhorn, Paula T. TI National Heart, Lung, and Blood Institute-Initiated Program "Interventions to Improve Hypertension Control Rates in African Americans" Background and Implementation SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE hypertension; clinical trials, randomized; cardiovascular diseases; prevention & control; risk factors ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; PRESSURE-MEASUREMENT; 7TH REPORT; PREVENTION; OUTCOMES; CHLORTHALIDONE; PREDICTORS; COMMITTEE; BLACK C1 NHLBI, Rockledge Ctr 2, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Einhorn, PT (reprint author), NHLBI, Rockledge Ctr 2, Div Prevent & Populat Sci, Room 10222,6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. EM einhornp@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 35 TC 9 Z9 9 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2009 VL 2 IS 3 BP 236 EP 240 DI 10.1161/CIRCOUTCOMES.109.850008 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575NN UT WOS:000276074000016 PM 20031843 ER PT J AU Sviridov, D Owen, WE Roberts, WL Edelman, LS Drake, SK Hortin, GL AF Sviridov, Denis Owen, William E. Roberts, William L. Edelman, L. S. Drake, Steven K. Hortin, Glen L. TI Proteinuria without albuminuria: Urinary protein excretion by a subset of patients with burn injuries SO CLINICA CHIMICA ACTA LA English DT Article DE Urine albumin; Burn injury; Albuminuria; Proteinuria; Acute phase proteins ID LIQUID-CHROMATOGRAPHY; GROWTH-HORMONE; SERUM-ALBUMIN; HPLC ASSAY; MICROALBUMINURIA; SIZE; IMMUNONEPHELOMETRY; FRAGMENTATION; INFLAMMATION; PREDICTOR AB Background: There is disagreement regarding the utility of urinary albumin excretion as a marker for capillary injury in patients with severe burn injuries. We examined protein components in urine specimens from patients with burn injury. Methods: Detailed analysis was performed for a set of 5 urine specimens selected based on a high ratio of albumin-sized molecules by size-exclusion HPLC (Accumin(R)) versus albumin by immunoassay methods. Specimens were analyzed for total protein, alpha(1)-microglobulin, alpha(1)-acid glycoprotein, cystatin C, and retinol-binding protein. Urine components were analyzed by chromatographic and electrophoretic methods. Major components were identified by mass spectrometry of tryptic peptides. Results: A subset of urine specimens had increased total protein with slight increases in albumin by immunoassay or by polyacrylamide gel electrophoresis. Albumin values by size-exclusion HPLC were more than 10-fold higher. Immunoassays for alpha(1)-microglobulin and alpha(1)-acid glycoprotein yielded concentrations 5-10 fold higher than for albumin. Other major components identified included zinc-alpha(2)-glycoprotein and leucine-rich-alpha(2)-glycoprotein. Conclusions: A subset of patients with burn injury had increased total urinary protein resulting primarily from increased excretion of proteins such as alpha(1)-microglobulin and alpha(1)-acid glycoprotein with little increase in albumin excretion. The unusual composition of urinary proteins in these patients may relate to decreased filtered load of albumin and increased filtered load of acute phase reactants or to alterations in renal tubular protein processing. Thus, measurement of urinary albumin may have decreased sensitivity for detecting kidney injury in burn patients. Published by Elsevier B.V. C1 [Sviridov, Denis; Hortin, Glen L.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Owen, William E.] ARUP Labs, Salt Lake City, UT 84108 USA. [Roberts, William L.] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA. [Edelman, L. S.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Drake, Steven K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), Univ Florida, Coll Med, Dept Pathol, POB 100275, Gainesville, FL 32610 USA. EM ghortin@pathology.ufl.edu FU Clinical Center; National Institutes of Health; Department of Health and Human Services; ARUP Institute for Clinical and Experimental Pathology FX Studies were supported by the intramural research program of the Clinical Center, National Institutes of Health, Department of Health and Human Services, and by the ARUP Institute for Clinical and Experimental Pathology. NR 35 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2009 VL 403 IS 1-2 BP 42 EP 46 DI 10.1016/j.cca.2009.01.012 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 447KN UT WOS:000266190100007 PM 19361474 ER PT J AU Homma, S Koido, S Sagawa, Y Suzuki, H Komita, H Nagasaki, E Takahara, A Horiguchi-Yamada, J Tajiri, H Zeldin, DC Obata, T AF Homma, S. Koido, S. Sagawa, Y. Suzuki, H. Komita, H. Nagasaki, E. Takahara, A. Horiguchi-Yamada, J. Tajiri, H. Zeldin, D. C. Obata, T. TI Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE dendritic cell; immune regulation; liver cancer; MHC class II; T(reg) ID CD4(+) T-CELLS; RESTRICTED TUMOR-ANTIGENS; DENDRITIC CELLS; IN-VIVO; MOLECULAR-CLONING; SUPPRESSOR-CELLS; CANCER PATIENTS; RESPONSES; IDENTIFICATION; TOLERANCE AB Cytochrome P450 2J subfamily (CYP2J) enzymes expressed in mouse hepatocellular carcinoma (HCC) cells were identified as an antigen recognized by specific CD4(+) T cells and the structure of its T cell epitope was determined by proteomics-based exploration. The major histocompatibility complex (MHC) class II binding peptides were isolated from I-A(k)/peptide complex of dendritic cells (DCs) loaded or unloaded with MIH-2 mouse HCC cells. MHC class II-binding peptides found in MIH-2-loaded DCs but not in unloaded DCs were determined by tandem mass spectrometric analysis. The peptide, consisting of amino acid 276-290 (DFIDAFLKEMTKYPE) of mouse CYP2J enzymes, was identified as an antigenic peptide presented in the context of MHC class II. Preventive treatment of mice with CYP2J peptide stimulated interferon (IFN)-gamma production of splenocytes and suppressed the growth of implanted CYP2J-positive MIH-2 cells but not CYP2J-negative murine bladder tumour cells. However, continuous treatment of MIH-2-bearing mice with CYP2J peptide significantly suppressed IFN-gamma production of splenocytes and accelerated the growth of implanted MIH-2 tumours in vivo. Increased frequencies of CD4(+)forkhead box P3 regulatory T cells and CD11b(+)Gr-1(+) myeloid suppressor cells were observed in splenocytes from the continuously immunized mice. These results indicate that antigenecity of CYP2J isoforms expressed in HCC cells activate host anti-tumour immunity at an initial stage of HCC, but suppress host anti-tumour immunity with excessive antigenic stimulation at an advanced stage. C1 [Homma, S.] Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med,Minato Ku, Tokyo 1058461, Japan. [Obata, T.] Jikei Univ, Sch Med, Dept Mol Cell Biol, Inst DNA Med, Tokyo 1058461, Japan. [Koido, S.; Suzuki, H.; Komita, H.; Nagasaki, E.; Takahara, A.; Tajiri, H.] Jikei Univ, Sch Med, Dept Internal Med, Tokyo 1058461, Japan. [Zeldin, D. C.] NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Homma, S (reprint author), Jikei Univ, Sch Med, Dept Oncol, Inst DNA Med,Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan. EM sahya@jikei.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Medical Association; Takeda Science Foundation; Pancreas Research Foundation of Japan; Jikei University Research Fund; Promotion and Mutual Aid Corporation for Private School of Japan; Science Research Promotion Fund; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This work was supported by Grants-in-Aid for Scientific Research (C) and (B), and a Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grants-in-Aid from the Japan Medical Association, the Takeda Science Foundation, the Pancreas Research Foundation of Japan, the Jikei University Research Fund, the Promotion and Mutual Aid Corporation for Private School of Japan and the Science Research Promotion Fund. This work was also supported, in part, with funds from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 40 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2009 VL 156 IS 2 BP 344 EP 352 DI 10.1111/j.1365-2249.2009.03900.x PG 9 WC Immunology SC Immunology GA 430ZZ UT WOS:000265032400023 PM 19302243 ER PT J AU Cecchini, S Negrete, A Virag, T Graham, BS Cohen, JI Kotin, RM AF Cecchini, Sylvain Negrete, Alejandro Virag, Tamas Graham, Barney S. Cohen, Jeffrey I. Kotin, Robert M. TI Evidence of Prior Exposure to Human Bocavirus as Determined by a Retrospective Serological Study of 404 Serum Samples from Adults in the United States SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; RESPIRATORY-TRACT INFECTIONS; REAL-TIME PCR; FELINE PANLEUKOPENIA VIRUS; VP1 CAPSID PROTEIN; INSECT CELLS; CLINICAL CHARACTERISTICS; EPIDEMIOLOGIC PROFILE; PHYLOGENETIC ANALYSIS; FREQUENT DETECTION AB Recently, molecular screening for pathogenic agents has identified a partial genome of a novel parvovirus, called human bocavirus (HBoV). The presence of this newly described parvovirus correlated with upper and lower respiratory tract infections in children. Lower respiratory tract infections are a leading cause of hospital admission in children, and the etiological agent has not been identified in up to 39% of these cases. Using baculovirus expression vectors (BEVs) and an insect cell system, we produced virus-like particles (VLPs) of HBoV. The engineered BEVs express the HBoV capsid proteins stoichiometrically from a single open reading frame. Three capsid proteins assemble into the VLP rather than two proteins predicted from the HBoV genome sequence. The denatured capsid proteins VP1, VP2, and VP3 resolve on silver-stained sodium dodecyl sulfate-polyacrylamide gels as three bands with apparent molecular masses of 72 kDa, 68 kDa, and 62 kDa, respectively. VP2 apparently initiates at a GCT codon (alanine) 273 nucleotides downstream from the VP1 start site and 114 nucleotides upstream from the VP3 initiation site. We characterized the stable capsids using physical, biochemical, and serological techniques. We found that the density of the VLP is 1.32 g/cm(3) and is consistent with an icosahedral symmetry with approximately a 25-nm diameter. Rabbit antiserum against the capsid of HBoV, which did not cross-react with adeno-associated virus type 2, was used to develop enzyme-linked immunosorbent assays (ELISAs) for anti-HBoV antibodies in human serum. Using ELISA, we tested 404 human serum samples and established a range of antibody titers in a large U.S. adult population sample. C1 [Cecchini, Sylvain; Negrete, Alejandro; Virag, Tamas; Kotin, Robert M.] NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. [Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Cohen, Jeffrey I.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10,Rm 7D05,10 Ctr Dr, Bethesda, MD 20892 USA. EM kotinr@nhlbi.nih.gov RI kotin, robert/B-8954-2008 FU National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases. NR 53 TC 16 Z9 17 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2009 VL 16 IS 5 BP 597 EP 604 DI 10.1128/CVI.00470-08 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 441DM UT WOS:000265749500001 PM 19244471 ER PT J AU Burbelo, PD Leahy, HP Groot, S Bishop, LR Miley, W Iadarola, MJ Whitby, D Kovacs, JA AF Burbelo, Peter D. Leahy, Hannah P. Groot, Sandra Bishop, Lisa R. Miley, Wendell Iadarola, Michael J. Whitby, Denise Kovacs, Joseph A. TI Four-Antigen Mixture Containing V-Cyclin for Serological Screening of Human Herpesvirus 8 Infection SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; KAPOSIS-SARCOMA; IMMUNOFLUORESCENCE ASSAYS; DIAGNOSIS; PROTEINS; SEROPREVALENCE; AUTOANTIBODIES; TUMORIGENESIS; TRANSMISSION AB Improved diagnostic reagents and testing are currently needed for the serological detection of human herpesvirus 8 (HHV-8) infections. We evaluated the luciferase immunoprecipitation systems (LIPS) for profiling antibody responses to a panel of HHV-8 proteins for diagnosis of Kaposi sarcoma (KS)-infected individuals. Using a pilot serum set, LIPS detected robust antibody responses to several known antigens, and a screen of 14 additional HHV-8 proteins identified v-cyclin as a potentially new diagnostic antigen. In evaluating a training-serum set, a four-antigen panel (K8.1, v-cyclin, ORF65, and a LANA fragment) was found to provide sufficient information for diagnosis. Analysis of a validation serum set using the combined results from these four separate antigen tests showed 100% sensitivity and 100% specificity. Furthermore, a LIPS format using a mixture of the four antigens, which simplifies data collection and analysis, closely matched the diagnostic performance of the combined separate tests (R = 0.95). This four-antigen mixture format analyzed with the validation serum set also showed 100% sensitivity and 100% specificity but was not statistically different from two separate enzyme-linked immunosorbent assays (94% sensitivity and 100% specificity) using baculovirus-produced LANA and bacterially produced K8.1. Heat map analysis of KS patient antibody titers revealed marked heterogeneity in humoral responses to this four-antigen panel. Overall, the LIPS assay showed 97% sensitivity, and positive anti-v-cyclin antibodies were detected in approximately 75% of the KS sera. These results suggest that LIPS screening using an antigen mixture is a sensitive and high-throughput method for serological screening of HHV-8 infection in individuals with KS. C1 [Burbelo, Peter D.; Leahy, Hannah P.; Groot, Sandra; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, Bethesda, MD 20892 USA. [Miley, Wendell; Whitby, Denise] NCI Frederick, Viral Oncol Sect, AIDS & Canc Virus Program, Sci Applicat Int Corp Frederick, Frederick, MD USA. [Bishop, Lisa R.; Kovacs, Joseph A.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Bldg 49,Room 1C20,49 Convent Dr, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov FU Division of Intramural Research; National Institute of Dental and Craniofacial Research; Clinical Center; NIH Clinical Research Center; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and the Clinical Center, in part by a Bench to Bedside award from the NIH Clinical Research Center, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. NR 26 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2009 VL 16 IS 5 BP 621 EP 627 DI 10.1128/CVI.00474-08 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 441DM UT WOS:000265749500004 PM 19261774 ER PT J AU Moreau, NG Li, L Geaghan, JP Damiano, DL AF Moreau, Noelle G. Li, Li Geaghan, James P. Damiano, Diane L. TI Contributors to fatigue resistance of the hamstrings and quadriceps in cerebral palsy SO CLINICAL BIOMECHANICS LA English DT Article DE Muscle fatigue; Muscle strength; Rehabilitation; Muscle spasticity; Cocontraction; Weakness ID MUSCLE FATIGUE; CONTRACTILE PROPERTIES; SPASTIC MUSCLE; VOLUNTARY; CHILDREN; STRENGTH; STROKE; FATIGABILITY; COACTIVATION; HEMIPARESIS AB Background: The purpose of this study was to elucidate relationships between quadriceps and hamstrings voluntary muscle fatigue and upper motor lesion impairments in cerebral palsy in order to gain a better understanding of their contribution to the observed fatigue resistance. Methods: Seventeen ambulatory subjects with cerebral palsy (mean age: 17.0, SD = 4.8 years) were recruited. Quantitative measures of strength, spasticity, cocontraction, and stiffness for both muscle groups were collected on an isokinetic dynamometer and entered in a factor analysis. The resulting factors were used as independent variables in a multiple regression analysis with quadriceps and hamstrings fatigue as dependent variables. Findings: Five independent factors explained 90% of the variance. in order of loadings, higher hamstring cocontraction and spasticity and lower hamstring strength were associated with lower levels of hamstring fatigue. Higher quadriceps cocontraction and lower quadriceps strength were the most predictive of lower levels of quadriceps fatigue. Interpretation: Greater motor impairments of the agonist muscle, particularly cocontraction, spasticity, and weakness, were associated with lower rates of muscle fatigue of the same muscle during performance of a voluntary fatigue protocol for the hamstrings and quadriceps. Muscles are highly adaptable; therefore, the results of this study suggest that the observed fatigue resistance may be due to the effect of the primary neural insult on motor unit recruitment and rate modulation or the result of secondary adaptations to spasticity, weakness, or excessive cocontraction. (c) 2009 Elsevier Ltd. All rights reserved. C1 [Moreau, Noelle G.] Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. [Moreau, Noelle G.] Washington Univ, Dept Phys Therapy, St Louis, MO USA. [Li, Li] Louisiana State Univ, Dept Kinesiol, Baton Rouge, LA 70803 USA. [Geaghan, James P.] Louisiana State Univ, Dept Expt Stat, Baton Rouge, LA 70803 USA. [Damiano, Diane L.] Natl Inst Hlth Clin Ctr, Dept Rehabil Med, Bethesda, MD USA. RP Moreau, NG (reprint author), Med Univ S Carolina, Dept Hlth Profess, 77 President St,MSC 700, Charleston, SC 29425 USA. EM moreau@musc.edu RI Damiano, Diane/B-3338-2010; Li, Li/B-8030-2008 OI Damiano, Diane/0000-0002-2770-5356; FU National Center for Medical Rehabilitation Research/National Institutes of Health [T32HD007434-16] FX Noelle G. Moreau submitted this research as partial fulfillment of the requirements for the degree of Doctor of Philosophy at Louisiana State University. This research was partially supported by the APTA Section on Pediatrics Clinical Research Grant and the Louisiana Board of Regents Fellowship. Dr. Moreau was also supported by a National Center for Medical Rehabilitation Research/National Institutes of Health Grant (T32HD007434-16) at Washington University in St. Louis during the writing of this manuscript. NR 44 TC 15 Z9 15 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD MAY PY 2009 VL 24 IS 4 BP 355 EP 360 DI 10.1016/j.clinbiomech.2009.01.012 PG 6 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 437FL UT WOS:000265472000005 PM 19264384 ER PT J AU Shaffer, AL Emre, NCT Romesser, PB Staudt, LM AF Shaffer, Arthur L. Emre, N. C. Tolga Romesser, Paul B. Staudt, Louis M. TI IRF4: Immunity. Malignancy! Therapy? SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; INTERFERON-REGULATORY FACTOR-4; SEQUENCE-BINDING-PROTEIN; CLASS-SWITCH RECOMBINATION; TRANSCRIPTION FACTOR; MULTIPLE-MYELOMA; GENE-EXPRESSION; KAPPA-B; T-CELLS; TERNARY COMPLEX AB IRF4, a member of the Interferon Regulatory Factor (IRF) family of transcription factors, is expressed in cells of the immune system, where it transduces signals from various receptors to activate or repress gene expression. IRF4 expression is a key regulator of several steps in lymphoid-, myeloid-, and dendritic-cell differentiation, including the differentiation of mature B cells into antibody-secreting plasma cells. IRF4 expression is also associated with many lymphoid malignancies, with recent evidence pointing to an essential role in multiple myeloma, a malignancy of plasma cells. Interference with IRF4 expression is lethal to multiple myeloma cells, irrespective of their genetic etiology, making IRF4 an "Achilles' heel" that may be exploited therapeutically. C1 [Shaffer, Arthur L.; Emre, N. C. Tolga; Romesser, Paul B.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Romesser, Paul B.] Natl Inst Hlth Res Scholars Program, Howard Hughes Med Inst, Bethesda, MD USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, Natl Inst Hlth, Bldg 10,Room 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Romesser, Paul/0000-0001-8268-2903 FU National Institutes of Health (NIH); National Cancer Institute; Center for Cancer Research FX Grant support: Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, Center for Cancer Research. P.R. is a Howard Hughes Medical Institute-NIH Research Scholar. NR 87 TC 86 Z9 92 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 2954 EP 2961 DI 10.1158/1078-0432.CCR-08-1845 PG 8 WC Oncology SC Oncology GA 440PL UT WOS:000265712100002 PM 19383829 ER PT J AU Chung, EJ Brown, AP Asano, H Mandler, M Burgan, WE Carter, D Camphausen, K Citrin, D AF Chung, Eun Joo Brown, Aaron P. Asano, Hiroaki Mandler, Mariana Burgan, William E. Carter, Donna Camphausen, Kevin Citrin, Deborah TI In vitro and In vivo Radiosensitization with AZD6244 (ARRY-142886), an Inhibitor of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase 1/2 Kinase SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN SQUAMOUS CARCINOMA; DNA-DAMAGE CHECKPOINT; IONIZING-RADIATION; HEPATOCELLULAR-CARCINOMA; PROSTATE-CANCER; RAS ONCOGENES; CELL LINES; H-RAS; ARREST; IRRADIATION AB Purpose: The mitogen-activated protein (MAP) kinase pathway is important for cell proliferation, survival, and differentiation, and is frequently up-regulated in cancers. The MAP kinase pathway is also activated after exposure to ionizing radiation. We investigated the effects of AZD6244 (ARRY-142886), an inhibitor of MAP kinase/extracellular signal-regulated kinase 1/2, on radiation response. Experimental Design: The effects of AZD6244 on the in vitro radiosensitivity of human cancer cell lines (A549, MiaPaCa2, and DU145) were evaluated using clonogenic assays. DNA damage repair was evaluated using gamma H2AX, and mitotic catastrophe was measured using nuclear fragmentation. Cell cycle effects were measured with flow cytometry. Growth delay was used to evaluate the effects of AZD6244 on in vivo tumor radiosensitivity. Results: Exposure of each cell line to AZD6244 before irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1, ranging from 1.16 to 2.0. No effects of AZD6244 on radiation-induced apoptosis or persistence of gamma H2AX foci after irradiation were detected. Cells treated with AZD6244 had an increased mitotic index and decreased Chk1 phosphorylation at 1 and 2 hours after irradiation. Mitotic catastrophe was increased in cells receiving AZD6244 and irradiation compared with the single treatments. In vivo studies revealed that AZD6244 administration to mice bearing A549 tumor xenografts resulted in a greater than additive increase in radiation-induced tumor growth delay (dose enhancement factor of 3.38). Conclusions: These results indicate that AZD6244 can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an increase in mitotic catastrophe. C1 [Chung, Eun Joo; Asano, Hiroaki; Mandler, Mariana; Camphausen, Kevin; Citrin, Deborah] NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Brown, Aaron P.] NIH, Off Director, Bethesda, MD 20892 USA. [Burgan, William E.; Carter, Donna] NCI, Mol Radiat Therapeut Branch & Sci Applicat Int Co, Frederick, MD 21701 USA. RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Bldg 10 Clinical Res Ctr,B2-3500, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov FU NIH; National Cancer Institute; Clinical Research Training Program; Pfizer, Inc. FX Grant support: Intramural Research Program of the NIH, National Cancer Institute, and the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer, Inc. (via a grant to the Foundation for NIH from Pfizer, Inc., A. Brown). NR 33 TC 44 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3050 EP 3057 DI 10.1158/1078-0432.CCR-08-2954 PG 8 WC Oncology SC Oncology GA 440PL UT WOS:000265712100013 PM 19366835 ER PT J AU Fakih, MG Pendyala, L Fetterly, G Toth, K Zwiebel, JA Espinoza-Delgado, I Litwin, A Rustum, YM Ross, ME Holleran, JL Egorin, MJ AF Fakih, Marwan G. Pendyala, Lakshmi Fetterly, Gerald Toth, Karoli Zwiebel, James A. Espinoza-Delgado, Igor Litwin, Alan Rustum, Youcef M. Ross, Mary Ellen Holleran, Julianne L. Egorin, Merrill J. TI A Phase I, Pharmacokinetic and Pharmacodynamic Study on Vorinostat in Combination with 5-Fluorouracil, Leucovorin, and Oxaliplatin in Patients with Refractory Colorectal Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE-DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; CETUXIMAB PLUS IRINOTECAN; HUMAN COLON-CANCER; ANTICANCER AGENTS; GENE-EXPRESSION; HDAC INHIBITION; TRIAL; FLUOROURACIL AB Purpose: We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX). Experimental Design: Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied. Results: Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed close-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR. Conclusions: The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression. C1 [Fakih, Marwan G.; Pendyala, Lakshmi; Fetterly, Gerald; Ross, Mary Ellen] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Toth, Karoli; Rustum, Youcef M.] Roswell Pk Canc Inst, Dept Pharmacol, Buffalo, NY 14263 USA. [Litwin, Alan] Roswell Pk Canc Inst, Dept Radiol, Buffalo, NY 14263 USA. [Fakih, Marwan G.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Med, Buffalo, NY 14260 USA. [Zwiebel, James A.; Espinoza-Delgado, Igor] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Fakih, MG (reprint author), Roswell Pk Canc Inst, Dept Med, Elm & Carlton St, Buffalo, NY 14263 USA. EM marwan.fakih@roswellpark.org FU National Cane er Institute (NCI); Institutional Cancer Center [CA16056, N01-CO-124001, P30 CA47904]; American Cancer Society [MRSG-04-270-01] FX Cancer Therapy Evaluation Program, the National Cancer Institute (NCI); an Institutional Cancer Center Support Grant CA16056; an American Cancer Society Grant MRSG-04-270-01; NCI contract N01-CO-124001, subcontract 25XS115-Task Order 2; and NCI grant P30 CA47904. NR 39 TC 38 Z9 38 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3189 EP 3195 DI 10.1158/1078-0432.CCR-08-2999 PG 7 WC Oncology SC Oncology GA 440PL UT WOS:000265712100031 PM 19383814 ER PT J AU Penney, KL Salinas, CA Pomerantz, M Schumacher, FR Beckwith, CA Lee, GS Oh, WK Sartor, O Ostrander, EA Kurth, T Ma, J Mucci, L Stanford, JL Kantoff, PW Hunter, DJ Stampfer, MJ Freedman, ML AF Penney, Kathryn L. Salinas, Claudia A. Pomerantz, Mark Schumacher, Fredrick R. Beckwith, Christine A. Lee, Gwo-Shu Oh, William K. Sartor, Oliver Ostrander, Elaine A. Kurth, Tobias Ma, Jing Mucci, Lorelei Stanford, Janet L. Kantoff, Philip W. Hunter, David J. Stampfer, Meir J. Freedman, Matthew L. TI Evaluation of 8q24 and 17q Risk Loci and Prostate Cancer Mortality SO CLINICAL CANCER RESEARCH LA English DT Article ID WIDE LINKAGE SCAN; CHROMOSOME 8Q24; RADICAL PROSTATECTOMY; AGGRESSIVENESS LOCI; GENETIC-VARIANTS; GLEASON SCORE; EARLY-ONSET; ASSOCIATION; CONFIRMATION; AMERICANS AB Purpose: Variants at chromosomal loci 8q24 and 17q are established risk factors for prostate cancer. Many studies have confirmed the findings for risk, but few have examined aggressiveness and other clinical variables in detail. Additionally, Gleason score is typically used as a surrogate for the primary end point of prostate cancer mortality. We investigated whether the 8q24 and 17q risk variants are associated with clinical variables as well as prostate cancer mortality. Experimental Design: In the Physicians' Health Study (1,347 cases and 1,462 controls), the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center; 3,714 cases), and the Fred Hutchinson Cancer Research Center King County Case-Control Studies (1,308 cases and 1,266 controls), we examined eight previously identified 8q24 and 17q risk variants for association with prostate cancer mortality in men of European ancestry. We considered associations with other surrogate markers of prostate cancer aggressiveness, such as Gleason score, pathologic stage, prostate-specific antigen at diagnosis, and age at diagnosis. Results: Six of the eight variants were confirmed as prostate cancer risk factors. Several variants were nominally associated with age at diagnosis; when totaling all alleles for single nucleotide polymorphisms significantly associated with risk, each additional allele decreased age at diagnosis by an average of 6 months in the Physicians' Health Study (P = 0.0005) and 4 months in the Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence (Gelb Center) cohort (P = 0.0016). However, there were no statistically significant associations with prostate cancer mortality. Conclusions: Our results suggest that the 8q24 and 17q prostate cancer risk variants may influence age at diagnosis but not disease aggressiveness. C1 [Pomerantz, Mark; Beckwith, Christine A.; Lee, Gwo-Shu; Oh, William K.; Kantoff, Philip W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Penney, Kathryn L.; Schumacher, Fredrick R.; Kurth, Tobias; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kurth, Tobias] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. [Ma, Jing; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Ma, Jing; Mucci, Lorelei; Hunter, David J.; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA USA. [Salinas, Claudia A.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Schumacher, Fredrick R.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Sartor, Oliver] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hunter, David J.; Freedman, Matthew L.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Hunter, David J.; Freedman, Matthew L.] Harvard Univ, Cambridge, MA 02138 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 710-C,44 Binney St, Boston, MA 02115 USA. EM freedman@broad.mit.edu RI Oh, William/B-9163-2012; Kurth, Tobias/A-9243-2012; OI Oh, William/0000-0001-5113-8147; Kurth, Tobias/0000-0001-7169-2620; Ostrander, Elaine/0000-0001-6075-9738 FU Dana-Farber Harvard Cancer Center Specialized Program [P50CA090381-06]; National Cancer Institute [CA56678, CA092579, CA097186, CA-34944, CA-40360, CA-097193]; National Heart, Lung, and Blood Institute [HL-26490, HL-34595]; National Research Service Awards [T32 CA009001-32, R25 CA098566] FX Dana-Farber Harvard Cancer Center Specialized Program of Research Excellence in Prostate Cancer grant P50CA090381-06. The Fred Hutchinson Cancer Research studies were supported by National Cancer Institute grants CA56678, CA092579, and CA097186. The Physicians' Health Study was supported by National Cancer Institute grants CA-34944, CA-40360, and CA-097193 and National Heart, Lung, and Blood Institute (Bethesda, MD) grants HL-26490 and HL-34595. K.L. Penney was supported by National Research Service Awards T32 CA009001-32 and R25 CA098566. F.R. Schumacher was supported by National Research Service Award T32 CA009001-32. NR 36 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3223 EP 3230 DI 10.1158/1078-0432.CCR-08-2733 PG 8 WC Oncology SC Oncology GA 440PL UT WOS:000265712100035 PM 19366828 ER PT J AU FitzGerald, LM Kwon, EM Koopmeiners, JS Salinas, CA Stanford, JL Ostrander, EA AF FitzGerald, Liesel M. Kwon, Erika M. Koopmeiners, Joseph S. Salinas, Claudia A. Stanford, Janet L. Ostrander, Elaine A. TI Analysis of Recently Identified Prostate Cancer Susceptibility Loci in a Population-based Study: Associations with Family History and Clinical Features SO CLINICAL CANCER RESEARCH LA English DT Article ID GENOME-WIDE ASSOCIATION; 5 GENETIC-VARIANTS; CHROMOSOME 8Q24; RISK LOCUS; AFRICAN-AMERICANS; SEQUENCE VARIANTS; MULTIPLE LOCI; CONFIRMATION; METAANALYSIS; RELATIVES AB Purpose: Two recent genome-wide association studies have highlighted several single nucleotide polymorphisms (SNPs) purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and the clinicopathologic features of the disease. Experimental Design: We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk stratified by family history of prostate cancer and clinicopathologic features of the disease was calculated with the use of logistic and polytomous regression. Results: These results confirm the importance of multiple, previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude with that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, whereas risk estimates for rs10993994 and rs5945619 varied by Gleason score. Conclusions: Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however, the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features. C1 [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Koopmeiners, Joseph S.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [FitzGerald, Liesel M.; Koopmeiners, Joseph S.; Salinas, Claudia A.; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 50,Room 5351,50 S Dr, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute, NIH [R01 CA56678, R01 CA92579, R01 CA082664, P50 CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX National Cancer Institute, NIH, grants R01 CA56678, R01 CA92579, R01 CA082664, and P50 CA097186, with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. NR 35 TC 44 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 1 PY 2009 VL 15 IS 9 BP 3231 EP 3237 DI 10.1158/1078-0432.CCR-08-2190 PG 7 WC Oncology SC Oncology GA 440PL UT WOS:000265712100036 PM 19366831 ER PT J AU Arant, CB Wessel, TR Ridker, PM Olson, MB Reis, SE Johnson, BD Sharaf, BL Pauly, DF Handberg, E Zineh, I Sopko, G Kelsey, SF Merz, CNB Pepine, CJ AF Arant, Christopher B. Wessel, Timothy R. Ridker, Paul M. Olson, Marian B. Reis, Steven E. Johnson, B. Delia Sharaf, Barry L. Pauly, Daniel F. Handberg, Eileen Zineh, Issam Sopko, George Kelsey, Sheryl F. Merz, C. Noel Bairey Pepine, Carl J. TI Multimarker Approach Predicts Adverse Cardiovascular Events in Women Evaluated for Suspected Ischemia: Results from the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation SO CLINICAL CARDIOLOGY LA English DT Article ID SYNDROME EVALUATION WISE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; CHEST-PAIN; INFLAMMATORY MARKERS; PILOT PHASE; DISEASE; BIOMARKERS; STRATEGY; THERAPY AB Background: Inflammatory marker and hemoglobin levels (eg biomarkers) considered separately, predict adverse events in selected populations. Hypothesis: A multiple biomarker approach predicts adverse events in women referred for evaluation of ischemia. Methods: We investigated associations between biomarkers (high sensitivity C-reactive protein, interleukin-6, serum amyloid-A, and hemoglobin levels) with adverse outcomes in women referred for coronary angiography for suspected ischemia in the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Women's Ischemia Syndrome Evaluation (WISE). Results: Among 595 women (mean age 58 years, ejection fraction [EF] 65%, majority without coronary stenosis >= 50%) followed for 3.6 +/- 1.8 years (mean +/- SD), those without abnormal markers had fewer events (11.6%) compared to those with 1 (18.4%), 2 (20.9%), Or 3 (37%) abnormal markers (p<0.001 for trend). Women without abnormal markers had fewer deaths (1.6%) than women with 1 (6.1%), 2 (9.1%), or 3 (17%) abnormal markers (p<0.001 for trend). Adding low hemoglobin was associated with higher adverse event and all-cause mortality rates. In multivariate analysis, as the number of abnormal biomarkers increased risk increased. Women with 3 or 4 abnormal biomarkers were approximately 10-20 times more likely to die (P<0.05). Biomarkers added to the predictive information provided by the Framingham Risk Score. Conclusions: Among women undergoing coronary angiography for suspected ischemia, a multibiomarker approach predicted adverse events. Biomarkers added prognostic information beyond that obtained from traditional risk factors. C1 [Arant, Christopher B.; Wessel, Timothy R.; Ridker, Paul M.; Handberg, Eileen; Pepine, Carl J.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32610 USA. [Zineh, Issam] Univ Florida, Coll Med, Coll Pharm, Dept Pharm Practice, Gainesville, FL 32610 USA. [Ridker, Paul M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Olson, Marian B.; Reis, Steven E.; Johnson, B. Delia; Kelsey, Sheryl F.] Univ Pittsburgh, Data Coordinating Ctr, Pittsburgh, PA USA. [Olson, Marian B.; Reis, Steven E.; Johnson, B. Delia; Kelsey, Sheryl F.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sharaf, Barry L.] Rhode Isl Hosp, Providence, RI USA. [Sopko, George] NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. [Merz, C. Noel Bairey] Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. RP Pepine, CJ (reprint author), Univ Florida, Coll Med, Div Cardiovasc Med, POB 100277, Gainesville, FL 32610 USA. EM pepincj@medicine.ufl.edu RI Reis, Steven/J-3957-2014 FU National Heart, Lung, and Blood Institutes [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, U0164829, U01 HL649141, U01 HL649241]; National Center for Research Resources [MO1-RR00425]; Gustavus and Louis Pfeiffer Research Foundation; Denville, New Jersey; Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California; Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania; Edythe L. Broad Endowment for Women's Heart Research, Los Angeles, California FX This work was supported by contracts from the National Heart, Lung, and Blood Institutes, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, a GCRC grant MO1-RR00425 from the National Center for Research Resources, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Denville, New Jersey, The Women's Guild of Cedars-Sinai Medical Center, Los Angeles, California, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, Pennsylvania, and The Edythe L. Broad Endowment for Women's Heart Research, Los Angeles, California. NR 18 TC 15 Z9 17 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 2009 VL 32 IS 5 BP 244 EP 250 DI 10.1002/clc.20454 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 448JQ UT WOS:000266259300004 PM 19452486 ER PT J AU Bruns, DE Knowler, WC AF Bruns, David E. Knowler, William C. TI Stabilization of Glucose in Blood Samples: Why It Matters SO CLINICAL CHEMISTRY LA English DT Editorial Material ID DIABETES-MELLITUS; DIAGNOSIS; FLUORIDE C1 [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Knowler, William C.] NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Bruns, DE (reprint author), Univ Virginia, Sch Med, Dept Pathol, POB 800168, Charlottesville, VA 22908 USA. EM dbruns@virginia.edu FU Intramural NIH HHS [ZIA DK069000-44] NR 10 TC 49 Z9 52 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2009 VL 55 IS 5 BP 850 EP 852 DI 10.1373/clinchem.2009.126037 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 438RA UT WOS:000265571900003 PM 19282352 ER PT J AU Song, EQ Zhang, ZL Luo, QY Lu, W Shi, YB Pang, DW AF Song, Er-Qun Zhang, Zhi-Ling Luo, Qing-Ying Lu, Wen Shi, Yun-Bo Pang, Dai-Wen TI Tumor Cell Targeting Using Folate-Conjugated Fluorescent Quantum Dots and Receptor-Mediated Endocytosis SO CLINICAL CHEMISTRY LA English DT Article ID IN-VITRO; MULTIFUNCTIONAL NANOSPHERES; CDSE NANOCRYSTALS; NANOPARTICLES; CYTOTOXICITY; VIVO; OLIGONUCLEOTIDES; TOXICITY; DELIVERY; PROTEIN AB BACKGROUND: Luminescent nanobioprobes with cell-targeting specificity are likely to find important applications in bioanalysis, biomedicine, and clinical diagnosis. Quantum dots (QDs) are unique and promising materials for such a purpose because of their fluorescence and large surface area for attaching cell-targeting molecules. METHODS: We produced water-dispersible QDs by coating hydrophobic QDs with small amphiphilic polyethylene glycol (PEG) molecules via hydrophobic interactions. We covalently Coupled folate (FA) onto the water-dispersible PEG-coated QDs (PEG-QDs) to produce FA-coupled PEG-QDs (FA-PEG-QDs). RESULTS: These FA-PEG-QD nanoparticles functioned as fluorescent nanobioprobes that specifically recognized folate receptors (FRs) overexpressed in human nasopharyngeal cells (KB cells) but not in an FR-deficient lung carcinoma cell line (A549 cells). Using confocal fluorescence microscopy, we demonstrated uptake of FA-PEG-QDs by KB cells but no uptake of folate-free PEG-QDs. The specificity of this receptor-mediated internalization was confirmed by comparing the uptake by KB vs A549 cells. CONCLUSIONS: Our results Suggest that Such cell-targeting fluorescent nanobioprobes are potentially very powerful tools for recognizing target cells and delivering and tracking drugs and other therapeutic materials. (C) 2009 American Association for Clinical Chemistry C1 [Song, Er-Qun; Zhang, Zhi-Ling; Luo, Qing-Ying; Lu, Wen; Pang, Dai-Wen] Wuhan Univ, Coll Chem & Mol Sci, Key Lab Analyt Chem Biol & Med, Minist Educ, Wuhan 430072, Peoples R China. [Song, Er-Qun; Zhang, Zhi-Ling; Luo, Qing-Ying; Lu, Wen; Pang, Dai-Wen] Wuhan Univ, State Key Lab Virol, Wuhan 430072, Peoples R China. [Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Pang, DW (reprint author), Wuhan Univ, Coll Chem & Mol Sci, Key Lab Analyt Chem Biol & Med, Minist Educ, Wuhan 430072, Peoples R China. EM dwpang@whu.edu.cn RI 林, 毅/E-5033-2011; Zhang, Zhi-Ling/B-3135-2010 OI Zhang, Zhi-Ling/0000-0001-7807-2264 FU National Key Scientific Program (973) - Nanoscience and Nanotechnology [2006CB933100]; Science Fund for Creative Research Groups of NSFC [20621502]; 863 Program [2006AA03Z320]; National Natural Science Foundation of China [30570490, 20833006]; Ministry of Education [306011, IRT0543]; Intramural Research Program of the National Institute of Child Health and Human Development, NIH, USA FX The National Key Scientific Program (973) - Nanoscience and Nanotechnology (2006CB933100), the Science Fund for Creative Research Groups of NSFC (20621502), the 863 Program (2006AA03Z320), the National Natural Science Foundation of China (30570490 and 20833006), the Ministry of Education (306011 and IRT0543), and the Intramural Research Program of the National Institute of Child Health and Human Development, NIH, USA. NR 40 TC 61 Z9 67 U1 4 U2 40 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2009 VL 55 IS 5 BP 955 EP 963 DI 10.1373/clinchem.2008.113423 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 438RA UT WOS:000265571900016 PM 19282359 ER PT J AU Laiyemo, AO Pinsky, PF Marcus, PM Lanza, E Cross, AJ Schatzkin, A Schoen, RE AF Laiyemo, Adeyinka O. Pinsky, Paul F. Marcus, Pamela M. Lanza, Elaine Cross, Amanda J. Schatzkin, Arthur Schoen, Robert E. TI Utilization and Yield of Surveillance Colonoscopy in the Continued Follow-Up Study of the Polyp Prevention Trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID COLORECTAL-CANCER; CLINICAL GUIDELINES; ADENOMA RECURRENCE; NATIONAL-SURVEY; HIGH-FIBER; BODY-SIZE; LOW-FAT; POLYPECTOMY; RATIONALE; PHYSICIANS AB Background and Aims:: Prospective information on the use and yield of surveillance colonoscopy is limited. We examined the use and yield of surveillance colonoscopy among participants in the Polyp Prevention Trial (PPT) after the 4-year dietary intervention trial ended. Methods: We followed a cohort of 1297 participants. We calculated the cumulative probability of posttrial colonoscopy and investigated the yield and predictive factors for adenoma and advanced adenoma recurrence over a mean time of 5.9 years. Results: Seven-hundred seventy-four subjects (59.7%) had a repeat colonoscopy. Among 431 subjects with low-risk adenomas (1-2 nonadvanced adenomas) at baseline and no adenoma recurrence at the end of the PPT (lowest-risk category), 30.3% underwent a repeat colonoscopy within 4 years. Among 55 subjects who had high-risk adenomas (advanced adenoma and/or >= 3 nonadvanced adenomas) at baseline and again at the final PPT colonoscopy (highest-risk category), 41.3% had a colonoscopy within 3 years and 63.5% had an examination within 5 years. The cumulative yield of advanced adenoma through 6 years was 3.6% for the lowest-risk category, 38.9% for the highest-risk category, and ranged from 6.6% to 13.8% for intermediate-risk categories. An advanced adenoma at the final PPT colonoscopy was associated significantly with an advanced adenoma recurrence during surveillance (hazard ratio, 6.2; 95% confidence interval, 2.5-15.4). Conclusions: Surveillance colonoscopy was overused for low-risk subjects and underused for high-risk subjects. Advanced adenoma yield corresponded with the adenoma risk category. Resource consumption can be better managed by aligning use with the risk of adenoma recurrence. C1 [Laiyemo, Adeyinka O.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol,Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Pinsky, Paul F.] NCI, Canc Prevent Div, Early Detect Res Grp, Bethesda, MD 20892 USA. [Lanza, Elaine] NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. [Cross, Amanda J.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Schoen, Robert E.] Dept Med & Epidemiol, Pittsburgh, PA USA. [Schoen, Robert E.] Univ Pittsburgh, Univ Pittsburgh Canc Inst, Pittsburgh, PA USA. RP Laiyemo, AO (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol,Biometry Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3121, Bethesda, MD 20892 USA. EM laiyemoa@mail.nih.gov FU Center for Cancer Research; Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health; Division of Cancer Prevention FX This study was funded by the Intramural Research Program of the Center for Cancer Research; the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health; and the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The funding agency had a role in the design and reporting of the study and in the decision to submit the manuscript for publication and approved the final version of the manuscript. NR 17 TC 55 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2009 VL 7 IS 5 BP 562 EP 567 DI 10.1016/j.cgh.2008.12.009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445RS UT WOS:000266069800014 PM 19138760 ER PT J AU Mutch, MG Schoen, RE Fleshman, JW Rall, CJN Dry, S Seligson, D Charabaty, A Chia, D Umar, A Viner, J Hawk, E Pinsky, PF AF Mutch, Matthew G. Schoen, Robert E. Fleshman, James W. Rall, Christopher J. N. Dry, Sarah Seligson, David Charabaty, Aline Chia, David Umar, Asad Viner, Jaye Hawk, Ernest Pinsky, Paul F. TI A Multicenter Study of Prevalence and Risk Factors for Aberrant Crypt Foci SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID PUTATIVE PRENEOPLASTIC LESIONS; INDUCED COLON CARCINOGENESIS; ISLAND METHYLATOR PHENOTYPE; SPORADIC COLORECTAL-CANCER; K-RAS MUTATIONS; QUANTIFICATION; IDENTIFICATION; INSTABILITY; ADENOMAS; ASPIRIN AB Background & Aims:: Aberrant crypt foci (ACF) are the putative precursor of colorectal adenomas. However, there are limited data available on the prevalence and risk factors for ACF. Methods: Subjects from the Prostate, Lung, Colorectal and Ovarian cancer screening trial were recruited for an ACF study, with subjects with adenoma history being oversampled. By using a standardized protocol of magnified chromoendoscopy with methylene blue staining (up to the middle rectal fold), ACF were photo-documented and removed for histologic evaluation. Results: A total of 505 (66% male; 55% >= 70 y) subjects from 4 institutions were examined; 42% had no adenoma, 32% had non-advanced distal adenoma, and 25% had advanced distal adenoma at the baseline Prostate, Lung, Colorectal and Ovarian cancer screening trial examination (8.2 years before ACF examination on average). A total of 68% of this population had 1 or more ACF, 43% had 1 to 3, 19% had 4 to 6, and 5% had 7 or more. Baseline adenoma status was not associated with ACF prevalence (range, 66%-69%) or mean number of ACF (range, 3.1-3.5). Of 143 endoscopic ACF examined histologically, 68.5% were confirmed to be ACF. In a logistic model, current (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-5.6) and former smoking (OR, 1.6; 95% CI, 1.1-2.5) were associated with higher ACF prevalence; a body mass index greater than 30 was associated with lower prevalence (OR, 0.53; 95% Cl, 0.35-0.8). Age, sex, family history of colorectal cancer, and aspirin/nonsteroidal anti-inflammatory drug use were not associated significantly with ACF prevalence. Conclusions: ACF prevalence and number were not associated with adenoma history, and only 68.5% of endoscopic ACF were confirmed histologically. These results raise concern about the use of ACF as a surrogate marker of colorectal cancer risk. C1 [Mutch, Matthew G.] Washington Univ, Sch Med, Dept Surg, Sect Colon & Rectal Surg, St Louis, MO 63110 USA. [Schoen, Robert E.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Rall, Christopher J. N.] Marshfield Clin Fdn Med Res & Educ, Dept Gastroenterol, Marshfield, WI USA. [Dry, Sarah; Seligson, David; Chia, David] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. [Charabaty, Aline] Georgetown Univ, Div Gastroenterol, Washington, DC USA. [Umar, Asad; Viner, Jaye; Pinsky, Paul F.] Natl Canc Inst, Canc Prevent Div, Bethesda, MD USA. [Hawk, Ernest] Univ Texas MD Anderson Canc Ctr, Div Canc Prevent & Populat Sci, Houston, TX USA. RP Mutch, MG (reprint author), Washington Univ, Sch Med, Dept Surg, Sect Colon & Rectal Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. FU National Cancer Institute [N01-CN2551] FX This research was supported under contract N01-CN2551 from the National Cancer Institute. NR 31 TC 24 Z9 27 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAY PY 2009 VL 7 IS 5 BP 568 EP 574 DI 10.1016/j.cgh.2009.01.016 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 445RS UT WOS:000266069800015 PM 19418605 ER PT J AU Vithayathil, J Gibney, G Baxevanis, AD Stubblefield, BK Sidransky, E Tayebi, N AF Vithayathil, J. Gibney, G. Baxevanis, A. D. Stubblefield, B. K. Sidransky, E. Tayebi, N. TI Glucocerebrosidase mutation H255Q appears to be exclusively in cis with D409H: structural implications SO CLINICAL GENETICS LA English DT Letter ID GAUCHER-DISEASE C1 [Vithayathil, J.; Stubblefield, B. K.; Sidransky, E.; Tayebi, N.] Natl Human Genome Res Inst, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gibney, G.; Baxevanis, A. D.] Natl Human Genome Res Inst, Genome Technol Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), Natl Human Genome Res Inst, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.ov FU Intramural NIH HHS [Z01 HG200336-03, Z01 HG200336-02] NR 8 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAY PY 2009 VL 75 IS 5 BP 503 EP 504 DI 10.1111/j.1399-0004.2009.01163.x PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 440NY UT WOS:000265708200017 PM 19459886 ER PT J AU Wheaton, L Fridman, E Bohlhalter, S Vorbach, S Hallett, M AF Wheaton, Lewis Fridman, Esteban Bohlhalter, Stephan Vorbach, Sherry Hallett, Mark TI Left parietal activation related to planning, executing and suppressing praxis hand movements SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Apraxia; ERP; ERD; Parietal; Praxis representations; Planning; Executing; Suppressing ID EVENT-RELATED DESYNCHRONIZATION; CORTICAL MOTOR SYSTEM; IDEOMOTOR APRAXIA; PREMOTOR AREAS; EEG COHERENCE; BRAIN-AREAS; GO/NO-GO; CORTEX; TASK; INHIBITION AB Objective: We sought to investigate the activity of bilateral parietal and premotor areas during a Go/No Go paradigm involving praxis movements of the dominant hand. Methods: A sentence was presented which instructed subjects on what movement to make (S1; for example, "Show me how to use a hammer."). After an 8-s delay, "Go" or "No Go" (S2) was presented. If Go, they were instructed to make the movement described in the SI instruction sentence as quickly as possible, and continuously until the "Rest" cue was presented 3 s later. If No Go, subjects were to simply relax until the next instruction sentence. Event-related potentials (ERP) and event-related desynchronization (ERD) in the beta band (18-22 Hz) were evaluated for three time bins: after SI, after S2, and from -2.5 to -1.5 s before the S2 period. Results: Bilateral premotor ERP was greater than bilateral parietal ERP after the S2 Go compared with the No Go. Additionally, left premotor ERP was greater than that from the right premotor area. There was predominant left parietal ERD immediately after S1 for both Go and No Go, which was sustained for the duration of the interval between SI and S2. For both S2 stimuli, predominant left parietal ERD was again seen when compared to that from the left premotor or right parietal area. However, the left parietal ERD was greater for Go than No Go. Conclusion: The results suggest a dominant role in the left parietal cortex for planning, executing, and suppressing praxis movements. The ERP and ERD show different patterns of activation and may reflect distinct neural movement-related activities. Significance: The data can guide further studies to determine the neurophysiological changes occurring in apraxia patients and help explain the unique error profiles seen in patients with left parietal damage. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ltd. All rights reserved. C1 [Wheaton, Lewis; Fridman, Esteban; Bohlhalter, Stephan; Vorbach, Sherry; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA. RP Wheaton, L (reprint author), Georgia Inst Technol, Sch Appl Physiol, Coll Sci, 281 Ferst Dr,Room 104, Atlanta, GA 30332 USA. EM law@gatech.edu RI Wheaton, Lewis /B-4482-2009; OI Wheaton, Lewis /0000-0003-0771-0294; Fridman, Esteban/0000-0001-7879-8874 FU NINDS; NIH FX This research was supported by the Intramural Research Program of the NINDS, NIH. Special thanks to Devee Schoenberg for professional editing. NR 41 TC 25 Z9 26 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD MAY PY 2009 VL 120 IS 5 BP 980 EP 986 DI 10.1016/j.clinph.2009.02.161 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 455JM UT WOS:000266755200022 PM 19345141 ER PT J AU Robbins, MS Szapocznik, J Horigian, VE Feaster, DJ Puccinelli, M Jacobs, P Burlew, K Werstlein, R Bachrach, K Brigham, G AF Robbins, Michael S. Szapocznik, Jose Horigian, Viviana E. Feaster, Daniel J. Puccinelli, Marc Jacobs, Petra Burlew, Kathy Werstlein, Robert Bachrach, Ken Brigham, Greg TI Brief strategic family therapy (TM) for adolescent drug abusers: A multi-site effectiveness study SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE BSFT (TM); Effectiveness trial; Adolescent; Drug abuse; Manualized ID RANDOMIZED-TRIALS; SUBSTANCE USE; PERFORMANCE; PREVALENCE AB Brief strategic family therapy (TM) (BSFT) is a manualized treatment designed to address aspects of family functioning associated with adolescent drug use and behavior problems (J. Szapocznik, U. Hervis, S. Schwartz, (2003). Brief strategic family therapy for adolescent drug abuse. (NIH Publication No. 03-4751). Bethesda, MD: National Institute on Drug Abuse). Within the National Institute on Drug Abuse's (NIDA's) Clinical Trials Network, BSFT is being compared to treatment as usual (TAU) in a multisite, prospective randomized clinical trial for drug using adolescents and their families in outpatient settings. The effectiveness of BSFT is being compared to TAU in reducing adolescent drug use, conduct problems, and sexually risky behaviors as well as in improving family functioning and adolescent prosocial behaviors. This paper describes the following aspects of the study: specific aims, research design and Study organization, assessment of primary and secondary outcomes, study treatments, data analysis plan, and data monitoring and safety reporting. (C) 2009 Elsevier Inc. All rights reserved. C1 [Robbins, Michael S.] Univ Miami, Miller Sch Med, Ctr Studies Family, Miami, FL 33136 USA. [Jacobs, Petra] Natl Inst Drug Abuse, Bethesda, MD USA. [Burlew, Kathy] Univ Cincinnati, Cincinnati, OH USA. [Werstlein, Robert] Daymark Recovery Serv, Salisbury, NC USA. [Bachrach, Ken] Tarzana Treatment Ctr Inc, Tarzana, CA USA. [Brigham, Greg] Maryhaven, Columbus, OH USA. RP Robbins, MS (reprint author), Univ Miami, Miller Sch Med, Ctr Studies Family, 1425 NW 10th Ave, Miami, FL 33136 USA. EM mrobbins@med.miami.edu RI Feaster, Daniel/I-6079-2013; OI Brigham, Gregory/0000-0003-1150-4493 FU NIDA [U10 DA 13720]; Jose Szapocznik, principal investigator FX This work supported by NIDA Grant (U10 DA 13720), Jose Szapocznik, principal investigator. NR 31 TC 14 Z9 15 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD MAY PY 2009 VL 30 IS 3 BP 269 EP 278 DI 10.1016/j.cct.2009.01.004 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 454HC UT WOS:000266672000011 PM 19470315 ER PT J AU Unoki, M Kumamoto, K Harris, CC AF Unoki, M. Kumamoto, K. Harris, C. C. TI ING Proteins as Potential Anticancer Drug Targets SO CURRENT DRUG TARGETS LA English DT Review DE ING2; oncogene; molecular targeted therapy; siRNA; small molecular compounds; cancer vaccine; cancer/testis antigen; oncoantigen ID CANDIDATE TUMOR-SUPPRESSOR; CELL-CYCLE ARREST; PHD FINGER PROTEINS; GROWTH-FACTOR-BETA; LUNG-CANCER; BREAST-CANCER; REPLICATIVE SENESCENCE; VACCINE THERAPIES; NAGNAG ACCEPTORS; SPLICE VARIANTS AB Recent emerging evidence suggests that ING family proteins play roles in carcinogenesis both as oncogenes and tumor suppressor genes depending on the family members and on cell status. Previous results from non-physiologic overexpression experiments showed that all five family members induce apoptosis or cell cycle arrest, thus it had been thought until very recently that all of the family members function as tumor suppressor genes. Therefore restoration of ING family proteins in cancer cells has been proposed as a treatment for cancers. However, ING2 knockdown experiments showed unexpected results: ING2 knockdown led to senescence in normal human fibroblast cells and suppressed cancer cell growth. ING2 is also overexpressed in colorectal cancer, and promotes cancer cell invasion through an MMP13 dependent pathway. Additionally, it was reported that ING2 has two isoforms, ING2a and ING2b. Although expression of ING2a predominates compared with ING2b, both isoforms confer resistance against cell cycle arrest or apoptosis to cancer cells, thus knockdown of both isoforms is critical to remove this resistance. Taken together, these results suggest that ING2 can function as an oncogene in some specific types of cancer cells, indicating restoration of this gene in cancer cells could cause cancer progression. Because knockdown of ING2 suppresses cancer cell invasion and induces apoptosis or cell cycle arrest, ING2 may be an anticancer drug target. In this brief review, we discuss possible clinical applications of ING2 with the latest knowledge of molecular targeted therapies. C1 [Unoki, M.; Kumamoto, K.; Harris, C. C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Unoki, M.] RIKEN, Inst Phys & Chem Res, Lab Biomarker, Tokyo 1088639, Japan. [Kumamoto, K.] Fukushima Med Univ, Sch Med, Dept Surg 2, Fukushima, Japan. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, Natl Inst Hlth, 37 Convent Dr,Bldg 37,Rm 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural NIH HHS [ZIA BC010875-02, Z01 BC010875-01] NR 88 TC 16 Z9 16 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD MAY PY 2009 VL 10 IS 5 BP 442 EP 454 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 440DT UT WOS:000265680600006 PM 19442116 ER PT J AU Wu, YL Brosh, RM AF Wu, Yuliang Brosh, Robert M., Jr. TI FANCJ Helicase Operates in the Fanconi Anemia DNA Repair Pathway and the Response to Replicational Stress SO CURRENT MOLECULAR MEDICINE LA English DT Review DE FANCJ; Fanconi anemia; breast cancer; cancer; DNA damage; DNA repair; helicase ID SISTER-CHROMATID COHESION; CROSS-LINK REPAIR; G-QUADRUPLEX DNA; BREAST-CANCER; HOMOLOGOUS RECOMBINATION; CAENORHABDITIS-ELEGANS; G4 DNA; DAMAGE RESPONSE; SACCHAROMYCES-CEREVISIAE; BACH1 PHOSPHOPEPTIDE AB Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to have direct roles in DNA metabolism. One of the more recently identified FA proteins, shown to be responsible for complementation of the FA complementation group J, is the BRCA1 Associated C-terminal Helicase (BACH1, designated FANCJ), originally identified as a protein associated with breast cancer. FANCJ has been proposed to function downstream of FANCD2 monoubiquitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination (HR) pathway of double strand break (DSB) repair. In this review, we will summarize the current knowledge in terms of FANCJ functions through its enzymatic activities and protein interactions. The molecular roles of FANCJ in DNA repair and the response to replicational stress will be discussed. C1 [Wu, Yuliang; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov FU NIH; National Institute on Aging; Fanconi Anemia Research Fund (RMB) FX This work was supported by the Intramural Research program of the NIH, National Institute on Aging and the Fanconi Anemia Research Fund (RMB). NR 106 TC 22 Z9 24 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5240 J9 CURR MOL MED JI Curr. Mol. Med. PD MAY PY 2009 VL 9 IS 4 BP 470 EP 482 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 440JS UT WOS:000265697200009 PM 19519404 ER PT J AU Ford, ES Puronen, CE Sereti, I AF Ford, Emily S. Puronen, Camille E. Sereti, Irini TI Immunopathogenesis of asymptomatic chronic HIV Infection: the calm before the storm SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE homeostasis; immune activation; T cells; T helper cell 17; type I interferons AB Purpose of review HIV and pathogenic simian immunodeficiency virus infection are characterized by chronic immune activation. This review addresses the factors that influence immune activation and may thus determine the rate of disease progression during the asymptomatic period of HIV. Recent findings Immune activation stems from foreign antigen stimulation, including HIV, microbial products and coinfections and compensatory homeostatic mechanisms. Continuous immune stimulation creates a permissive environment for further viral replication, while temporarily allowing successful replenishment of the T-cell pool. Type I interferon, microbial translocation, activated (but ineffective) effector T cells, unruly regulatory T cells and inadequate T helper 17 cells all play important roles in the cycle of activation, functional exhaustion and T-cell death that leads to immunodeficiency. Summary The asymptomatic chronic phase of HIV infection is a dynamic balance between host and virus, the outcome of which determines an individual's course of disease. Evaluation of the factors that determine the immunologic threshold of disease progression could assist in designing therapeutic strategies, including individualized timing of ART. C1 [Ford, Emily S.; Puronen, Camille E.; Sereti, Irini] NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Sereti, I (reprint author), 10 Ctr Dr,Bldg 10,Room 11B07A, Bethesda, MD 20892 USA. EM isereti@mail.nih.gov OI Ford, Emily/0000-0001-7358-798X FU NIH; Pfizer Inc. FX E.S.F. and C. E. P. are participants in the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer Inc. via a grant to the Foundation for NIH from Pfizer Inc. NR 108 TC 27 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2009 VL 4 IS 3 BP 206 EP 214 DI 10.1097/COH.0b013e328329c68c PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V19PA UT WOS:000208083100009 PM 19532052 ER PT J AU Nussenblatt, RB Liu, BY Li, ZQ AF Nussenblatt, Robert B. Liu, Baoying Li, Zhuqing TI Age-related macular degeneration: An immunologically driven disease SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Review DE Age-related macular degeneration; AMD; immune response; intraocular inflammatory disease ID COMPLEMENT FACTOR-H; C-REACTIVE PROTEIN; EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; RETINAL-PIGMENT EPITHELIUM; IMMUNE-RESPONSE; MACROPHAGE HETEROGENEITY; BRUCHS MEMBRANE; OCULAR-TISSUES; T-CELLS; ACTIVATION AB Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly individuals worldwide. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of AMD. This review discusses historical and more recent studies that have led to the recognition that AMD is an intraocular inflammatory disease, and that is possibly driven by an immune response. A particular focus of this review is recent studies on the contribution of the complement system and macrophages to the pathogenesis of AMD. A working hypothesis is also presented that may reconcile the current understanding of the pathogenesis of AMD and some apparently contradictory findings in the literature. C1 [Nussenblatt, Robert B.; Liu, Baoying; Li, Zhuqing] NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, NIH, Immunol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM DrBob@nei.nih.gov NR 91 TC 38 Z9 40 U1 1 U2 3 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD MAY PY 2009 VL 10 IS 5 BP 434 EP 442 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 441PY UT WOS:000265782500005 PM 19431076 ER PT J AU Vocci, FJ Montoya, ID AF Vocci, Frank J. Montoya, Ivan D. TI Psychological treatments for stimulant misuse, comparing and contrasting those for amphetamine dependence and those for cocaine dependence SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE amphetamine; behavioral; cocaine; methamphetamine; treatment ID CLINICAL-TRIALS NETWORK; SUBSTANCE USE DISORDERS; CONTINGENCY-MANAGEMENT; METHAMPHETAMINE DEPENDENCE; DRUG-ABUSE; BEHAVIORAL THERAPIES; ABSTINENCE; USERS; REINFORCEMENT; INCENTIVES AB Purpose of review The aim is to compare and contrast psychological treatments for amphetamine and cocaine dependence. Recent findings Stimulant dependence, in the form of cocaine or amphetamine/methamphetamine dependence, is prevalent worldwide, and their ratio may vary across different countries and regions of countries. The treatment of stimulant disorders has greatly advanced in recent years, and scientific evaluation of behavioral therapies, using randomized clinical trials designs and a stage-wise approach, have demonstrated the safety and efficacy of interventions. Psychological interventions such as cognitive behavioral therapy and contingency management for cocaine and methamphetamines use disorders are well tolerated and moderately effective in achieving drug abstinence. There is evidence that contingency management interventions can help to improve retention in treatment and, in turn, other treatment outcomes. Although there are important differences in the neuropsychiatric and medical consequences of cocaine and amphetamine use disorders, there is currently no evidence for a differential treatment effect of any psychosocial treatment in the management of these disorders. Summary As there are no Food and Drug Administration-approved medications for the treatment of these disorders, psychological interventions form the basis of their treatment. More research is needed to address the specific psychosocial needs of cocaine and amphetamine-dependent individuals in order to improve their treatment outcomes. C1 [Vocci, Frank J.] Friends Res Inst, Baltimore, MD USA. [Montoya, Ivan D.] Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Montoya, ID (reprint author), Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4131, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov FU NIDA FX This work was funded by NIDA. NR 33 TC 32 Z9 32 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 2009 VL 22 IS 3 BP 263 EP 268 DI 10.1097/YCO.0b013e32832a3b44 PG 6 WC Psychiatry SC Psychiatry GA 438MV UT WOS:000265560400003 PM 19307968 ER PT J AU Machado-Vieira, R Salvadore, G Ibrahim, LA Diaz-Granados, N Zarate, CA AF Machado-Vieira, Rodrigo Salvadore, Giacomo Ibrahim, Lobna A. Diaz-Granados, Nancy Zarate, Carlos A., Jr. TI Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE AMPA; antidepressant; bipolar disorder; depression; drug development; glutamate; metabotropic; NMDA ID MAJOR DEPRESSIVE DISORDER; METHYL-D-ASPARTATE; CELLULAR PLASTICITY CASCADES; AMPA RECEPTOR TRAFFICKING; FORCED SWIMMING TEST; OPEN-LABEL TRIAL; STAR-ASTERISK-D; BIPOLAR DISORDER; NMDA RECEPTOR; ANTIDEPRESSANT TREATMENT AB There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators. C1 [Machado-Vieira, Rodrigo; Salvadore, Giacomo; Ibrahim, Lobna A.; Diaz-Granados, Nancy; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Res Progr, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), 10 Ctr Dr,Mark O Hatfield CRC,Unit 7 SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health; NARSAD FX We would like to acknowledge the support of the Intramural Research Program of the National Institute of Mental Health and NARSAD. Dr. Zarate is listed among the inventors on a patent application submitted for the use of ketamine in depression. Ioline Henter provided invaluable editorial assistance. NR 156 TC 54 Z9 55 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD MAY PY 2009 VL 15 IS 14 BP 1595 EP 1611 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 441SV UT WOS:000265791700004 PM 19442176 ER PT J AU Shen, P Stewart, JH Levine, EA AF Shen, Perry Stewart, John H., IV Levine, Edward A. TI Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Overview and Rationale SO CURRENT PROBLEMS IN CANCER LA English DT Article ID RECURRENCE FOLLOWING SURGERY; ADVANCED OVARIAN-CANCER; QUALITY-OF-LIFE; MITOMYCIN-C; COLORECTAL-CANCER; GASTRIC-CANCER; INITIAL DISSEMINATION; CLINICAL-PATTERNS; TUMOR-CELLS; CARCINOMATOSIS C1 [Shen, Perry; Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. [Shen, Perry; Levine, Edward A.] Wake Forest Univ, Program Cytoreduct Surg, Winston Salem, NC USA. [Stewart, John H., IV] Assoc Amer Med Coll, Natl Advisory Comm, Washington, DC 20037 USA. [Stewart, John H., IV] NCI, Grant Review Comm, Bethesda, MD 20892 USA. [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Surg Oncol Res Lab, Winston Salem, NC USA. RP Shen, P (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. FU NCI NIH HHS [K08 CA131482] NR 62 TC 14 Z9 16 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2009 VL 33 IS 3 BP 125 EP 141 DI 10.1016/j.currproblcancer.2009.06.003 PG 17 WC Oncology SC Oncology GA 483SB UT WOS:000268987000002 PM 19647612 ER PT J AU Stewart, JH Levine, EA Shen, P AF Stewart, John H., IV Levine, Edward A. Shen, Perry TI The Current Role of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Dissemination of Appendiceal Tumors SO CURRENT PROBLEMS IN CANCER LA English DT Article ID QUALITY-OF-LIFE; PSEUDOMYXOMA-PERITONEI; CYTOREDUCTIVE SURGERY; COLORECTAL-CANCER; MITOMYCIN-C; PHASE-I; CLINICOPATHOLOGICAL ANALYSIS; MALIGNANT NEOPLASMS; PROGNOSTIC-FACTORS; COLON-CANCER C1 [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Surg Oncol Res Lab, Winston Salem, NC USA. [Stewart, John H., IV] Assoc Amer Med Coll, Natl Advisory Comm, Washington, DC 20037 USA. [Stewart, John H., IV] NCI, Grant Review Comm, Bethesda, MD 20892 USA. [Levine, Edward A.; Shen, Perry] Wake Forest Univ, Program Cytoreduct Surg, Winston Salem, NC USA. RP Stewart, JH (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. FU NCI NIH HHS [K08 CA131482] NR 47 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2009 VL 33 IS 3 BP 142 EP 153 DI 10.1016/j.currproblcancer.2009.06.002 PG 12 WC Oncology SC Oncology GA 483SB UT WOS:000268987000003 PM 19647613 ER PT J AU Shen, P Stewart, JH Levine, EA AF Shen, Perry Stewart, John H., IV Levine, Edward A. TI The Role of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Metastatic Colorectal Cancer with Peritoneal Surface Disease SO CURRENT PROBLEMS IN CANCER LA English DT Article ID LONG-TERM SURVIVAL; HEPATIC RESECTION; SYSTEMIC CHEMOTHERAPY; CARCINOMA METASTASES; LIVER METASTASES; RANDOMIZED-TRIAL; MANAGEMENT; RECURRENCE; THERAPY; ORIGIN C1 [Shen, Perry; Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. [Shen, Perry; Levine, Edward A.] Wake Forest Univ, Program Cytoreduct Surg, Winston Salem, NC USA. [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Surg Oncol Res Lab, Winston Salem, NC USA. [Stewart, John H., IV] Assoc Amer Med Coll, Natl Advisory Comm, Washington, DC 20037 USA. [Stewart, John H., IV] NCI, Grant Review Comm, Bethesda, MD 20892 USA. RP Shen, P (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. FU NCI NIH HHS [K08 CA131482] NR 29 TC 0 Z9 0 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2009 VL 33 IS 3 BP 154 EP 167 DI 10.1016/j.currproblcancer.2009.06.004 PG 14 WC Oncology SC Oncology GA 483SB UT WOS:000268987000004 PM 19647614 ER PT J AU Levine, EA Stewart, JH Shen, P AF Levine, Edward A. Stewart, John H., IV Shen, Perry TI Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy for Peritoneal Surface Malignancy: Non-Colorectal Indications SO CURRENT PROBLEMS IN CANCER LA English DT Review ID GYNECOLOGIC-ONCOLOGY-GROUP; RESIDUAL OVARIAN-CANCER; ADVANCED GASTRIC-CANCER; DIGESTIVE-TRACT CANCER; QUALITY-OF-LIFE; PHASE-III TRIAL; PSEUDOMYXOMA-PERITONEI; MITOMYCIN-C; PROGNOSTIC-FACTORS; SMALL-BOWEL C1 [Levine, Edward A.; Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. [Levine, Edward A.; Shen, Perry] Wake Forest Univ, Program Cytoreduct Surg, Winston Salem, NC USA. [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Surg Oncol Res Lab, Winston Salem, NC USA. [Stewart, John H., IV] Assoc Amer Med Coll, Natl Advisory Comm, Washington, DC 20037 USA. [Stewart, John H., IV] NCI, Grant Review Comm, Bethesda, MD 20892 USA. RP Levine, EA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. NR 103 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2009 VL 33 IS 3 BP 168 EP 193 DI 10.1016/j.currproblcancer.2009.06.005 PG 26 WC Oncology SC Oncology GA 483SB UT WOS:000268987000005 ER PT J AU Stewart, JH Shen, P Levine, EA AF Stewart, John H., IV Shen, Perry Levine, Edward A. TI Translation Considerations for Hyperthermic Intraperitoneal Chemotherapy SO CURRENT PROBLEMS IN CANCER LA English DT Article ID TUMOR-NECROSIS-FACTOR; PHASE-I TRIAL; PERITONEAL CARCINOMATOSIS; INDUCED APOPTOSIS; MITOMYCIN-C; HEAT; CANCER; CELLS; 5-FLUOROURACIL; PENETRATION C1 [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. [Stewart, John H., IV] Assoc Amer Med Coll, Natl Advisory Comm, Washington, DC 20037 USA. [Stewart, John H., IV] NCI, Grant Review Comm, Bethesda, MD 20892 USA. [Shen, Perry; Levine, Edward A.] Wake Forest Univ, Program Cytoreduct Surg, Winston Salem, NC USA. [Stewart, John H., IV] Wake Forest Univ, Bowman Gray Sch Med, Surg Oncol Res Lab, Winston Salem, NC USA. RP Stewart, JH (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Tumor Immunotherapy Program, Winston Salem, NC 27109 USA. FU NCI NIH HHS [K08 CA131482] NR 24 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD MAY-JUN PY 2009 VL 33 IS 3 BP 194 EP 202 DI 10.1016/j.currproblcancer.2009.06.006 PG 9 WC Oncology SC Oncology GA 483SB UT WOS:000268987000006 PM 19647616 ER PT J AU Kumar, M Mohania, D Kumar, A Nagpal, R Behare, PV Aggarwal, PK Yadav, M Marotta, F Jain, S Yadav, H AF Kumar, Manoj Mohania, Dheeraj Kumar, Ashok Nagpal, Ravinder Behare, P. V. Aggarwal, P. K. Yadav, Mukesh Marotta, Francesco Jain, Shalini Yadav, Hariom TI METABOLOMICS: AN EMERGING TOOL FOR NUTRITION RESEARCH SO CURRENT TOPICS IN NUTRACEUTICAL RESEARCH LA English DT Review DE Metabolomics; Nutrition; Food; Health; NMR; Mass spectroscopy ID TANDEM MASS-SPECTROMETRY; FUNCTIONAL GENOMICS; LIQUID-CHROMATOGRAPHY; MAGNETIC-RESONANCE; SYSTEMS BIOLOGY; HUMAN URINE; H-1-NMR SPECTROSCOPY; PATTERN-RECOGNITION; TUMORS DEFICIENT; HUMAN PLASMA AB Metabolomics is an emerging strategy of research in the field of medicine and biological sciences, which provide a platform to study small, endogenous metabolites in an organ, biofluid or whole organism. The development of metabolomics has been accelerated in the post genomic era, since these molecules report the interaction of genes and environment or the functional genome. The global analysis of metabolomics can execute the important information in the search of predictive disease biomarkers and can explore the understanding of diseases pathophysiology and development of molecular targeted therapeutics. Recently, the use of metabolomics in nutritional research has been increased because of intimate relationship between nutrients and metabolism. The purpose of this review is to summarize the importance and evaluate the obtained information from the application of metabolomics in nutritional research, commonly tools to analyze interaction of nutrients and metabolites and future potentials. C1 [Yadav, Hariom] NIDDK, Clin Res Ctr 5W5872, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Kumar, Manoj; Behare, P. V.; Aggarwal, P. K.] Natl Dairy Res Inst, Dairy Microbiol Div, Karnal 132001, Haryana, India. [Mohania, Dheeraj] Natl Dairy Res Inst, Anim Biochem Div, Karnal 132001, Haryana, India. [Kumar, Ashok] MLK PG Coll, Dept Zool, Balrampur 271201, Uttar Pradesh, India. [Nagpal, Ravinder] Lovely Profess Univ, Dept Biotechnol, Phagwara, Punjab, India. [Yadav, Mukesh] Coll Adv Studies, Datia, Madhya Pradesh, India. [Marotta, Francesco] GAIA Age Management Fdn, Nutraceut Nutrigenom Unit, Pavia, Italy. RP Yadav, H (reprint author), NIDDK, Clin Res Ctr 5W5872, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM yadavh@mail.nih.gov NR 60 TC 3 Z9 3 U1 0 U2 12 PU NEW CENTURY HEALTH PUBLISHERS, LLC PI COPPELL PA PO BOX 175, COPPELL, TX 75019 USA SN 1540-7535 J9 CURR TOP NUTRACEUT R JI Curr. Top. Nutraceutical Res. PD MAY PY 2009 VL 7 IS 2 BP 97 EP 104 PG 8 WC Nutrition & Dietetics; Pharmacology & Pharmacy SC Nutrition & Dietetics; Pharmacology & Pharmacy GA 500GZ UT WOS:000270288200007 ER PT J AU Telford, WG Subach, FV Verkhusha, VV AF Telford, William G. Subach, Fedor V. Verkhusha, Vladislav V. TI Supercontinuum White Light Lasers for Flow Cytometry SO CYTOMETRY PART A LA English DT Article DE flow cytometry; supercontinuum; white light laser; immunophenotyping; fluorescent protein; DsRed; mCherry; Katushka ID RED FLUORESCENT PROTEIN; YELLOW; SENSITIVITY; MICROSCOPE; GENERATION; EXCITATION; DIODES; ORANGE; FIBER AB Excitation of fluorescent probes for flow cytometry has traditionally been limited to a few discrete laser lines, an inherent limitation in our ability to excite the vast array of fluorescent probes available for cellular analysis. In this report, we have used a supercontinuum (SC) white light laser as an excitation source for flow cytometry. By selectively filtering the wavelength of interest, almost any laser wavelength in the visible spectrum can be separated and used for flow cytometric analysis. The white light lasers used in this study were integrated into a commercial flow cytometry platform, and a series of high-transmission bandpass filters used to select wavelength ranges from the blue (similar to 480 nm) to the long red (>700 nm). Cells labeled with a variety of fluorescent probes or expressing fluorescent proteins were then analyzed, in comparison with traditional lasers emitting at wavelengths similar to the filtered SC source. Based on a standard sensitivity metric, the white light laser bandwidths produced similar excitation levels to traditional lasers for a wide variety of fluorescent probes and expressible proteins. Sensitivity assessment using fluorescent bead arrays confirmed that the SC laser and traditional sources resulted in similar levels of detection sensitivity. Supercontinuum white light laser sources therefore have the potential to remove a significant barrier in flow cytometric analysis, namely the limitation of excitation wavelengths. Almost any visible wavelength range can be made available for excitation, allowing access to virtually any fluorescent probe, and permitting "fine-tuning" of excitation wavelength to particular probes. (c) 2008 International Society for Advancement of Cytometry C1 [Telford, William G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Subach, Fedor V.; Verkhusha, Vladislav V.] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. RP Telford, WG (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10 Room 3-3297,9000 Rockville Pike, Bethesda, MD 20892 USA. EM telfordw@mail.nih.gov RI Subach, Fedor/K-7080-2014 FU Center for Cancer Research; NCI/NIH; NIGMS/NIH [GM073913, GM070358] FX Grant sponsor: Center for Cancer Research, NCI/NIH; Grant sponsor: NIGMS/NIH; Grant number: GM073913, GM070358. NR 23 TC 17 Z9 17 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD MAY PY 2009 VL 75A IS 5 BP 450 EP 459 DI 10.1002/cyto.a.20687 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 436WH UT WOS:000265446300009 PM 19072836 ER PT J AU Vitiello, B AF Vitiello, Benedetto TI TREATMENT OF ADOLESCENT DEPRESSION: WHAT WE HAVE COME TO KNOW SO DEPRESSION AND ANXIETY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; TADS; METAANALYSIS; REMISSION; OUTCOMES; CHILDREN C1 [Vitiello, Benedetto] NIMH, Prevent Intervent Res Branch, Bethesda, MD 20892 USA. [Vitiello, Benedetto] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Vitiello, B (reprint author), NIMH, Prevent Intervent Res Branch, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 16 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD MAY PY 2009 VL 26 IS 5 BP 393 EP 395 DI 10.1002/da.20572 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 442XP UT WOS:000265874300001 PM 19404989 ER PT J AU Zielinski, DS Eckenrode, J Olds, DL AF Zielinski, David S. Eckenrode, John Olds, David L. TI Nurse home visitation and the prevention of child maltreatment: Impact on the timing of official reports SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID RANDOMIZED TRIAL; SEXUAL ABUSE; LIFE-COURSE; PROGRAM; NEGLECT; INTERVENTION; BEHAVIORS; SEVERITY; OUTCOMES; SUBTYPE AB This study examined the effects of the Nurse Family Partnership (NFP), a program of prenatal and infancy home visiting by nurses, on the timing of verified reports of child maltreatment. A sample of predominantly unmarried, low-income mothers and their first-born children were randomly assigned to receive either home visitation services by nurses beginning in pregnancy and lasting until the child was age 2, or comparison services. Previous studies have found that this program was effective in reducing the overall number of substantiated Child Protective Service reports by age 15. In the current study, survival analyses were used to assess temporal differences between nurse visited (n = 93) and comparison (n = 144) children's onset rates for maltreatment. The two groups' survival functions remained nearly identical until age 4, at which point the nurse-visited group's risk for onset began to significantly diminish. These results were more pronounced among the highest risk subgroup and among victims of neglect. The findings provide evidence that the NFP's success in reducing the number of maltreatment reports resulted in part from in its impact on the timing of the maltreatment process. C1 [Zielinski, David S.] Duke Univ, Durham, NC 27706 USA. [Eckenrode, John] Cornell Univ, Ithaca, NY 14853 USA. [Olds, David L.] Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. RP Zielinski, DS (reprint author), NIMH, Off Director, 6001 Execut Blvd,Room 8206, Bethesda, MD 20892 USA. EM dz17y@nih.gov FU NCI NIH HHS [90-CA-1631]; NIMH NIH HHS [1-K05-MH01382-01, R01-MH49381]; PHS HHS [96ASPE278A] NR 37 TC 16 Z9 16 U1 2 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD MAY PY 2009 VL 21 IS 2 BP 441 EP 453 DI 10.1017/S0954579409000248 PG 13 WC Psychology, Developmental SC Psychology GA 432HH UT WOS:000265123600006 PM 19338692 ER PT J AU Zosuls, KM Ruble, DN Tamis-LeMonda, CS Shrout, PE Bornstein, MH Greulich, FK AF Zosuls, Kristina M. Ruble, Diane N. Tamis-LeMonda, Catherine S. Shrout, Patrick E. Bornstein, Marc H. Greulich, Faith K. TI The Acquisition of Gender Labels in Infancy: Implications for Gender-Typed Play SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE gender development; self-socialization; language development; play; sex differences ID SEX-ROLE STEREOTYPES; PREDICTIVE-VALIDITY; YOUNG-CHILDREN; 2ND YEAR; LANGUAGE; TOYS; KNOWLEDGE; PREFERENCES; VOCABULARY; BEHAVIORS AB Two aspects of children's early gender development-the spontaneous production of gender labels and gender-typed play-were examined longitudinally in a sample of 82 children. Survival analysis, a statistical technique Well suited to questions involving developmental transitions. was used to investigate the timing of the onset of children's gender labeling as based on mothers' biweekly telephone interviews regarding their children's language from 9 through 21 months. Videotapes of children's play both alone and with mother during home visits at 17 and 21 months were independently analyzed for play with gender-stereotyped and gender-neutral toys. Finally. the relation between gender labeling and gender-typed play was examined. Children transitioned to using gender labels at approximately 19 months, on average. Although girls and boys showed similar patterns in the development of gender labeling, girls began labeling significantly earlier than boys. Modest sex differences in play were present at 17 months and increased at 21 months. Gender labeling predicted increases in gender-typed play, suggesting that knowledge of gender categories ought influence gender typing before the age of 2. C1 [Zosuls, Kristina M.; Ruble, Diane N.; Shrout, Patrick E.; Greulich, Faith K.] NYU, Dept Psychol, New York, NY 10003 USA. [Tamis-LeMonda, Catherine S.] NYU, Dept Appl Psychol, Steinhardt Sch Culture Educ & Human Dev, New York, NY 10003 USA. [Bornstein, Marc H.] NICHHD, Bethesda, MD 20892 USA. RP Zosuls, KM (reprint author), NYU, Dept Psychol, 6 Washington Pl, New York, NY 10003 USA. EM kmz205@nyu.edu FU Intramural NIH HHS; NICHD NIH HHS [HD20559, HD20807, R01 HD049994-24, 5R01HD49994-24, R01 HD049994] NR 83 TC 51 Z9 52 U1 8 U2 49 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 2009 VL 45 IS 3 BP 688 EP 701 DI 10.1037/a0014053 PG 14 WC Psychology, Developmental SC Psychology GA 440WT UT WOS:000265731100007 PM 19413425 ER PT J AU Pechhold, K Zhu, XL Harrison, VS Lee, J Chakrabarty, S Koczwara, K Gavrilova, O Harlan, DM AF Pechhold, Klaus Zhu, Xiaolong Harrison, Victor S. Lee, Janet Chakrabarty, Sagarika Koczwara, Kerstin Gavrilova, Oksana Harlan, David M. TI Dynamic Changes in Pancreatic Endocrine Cell Abundance, Distribution, and Function in Antigen-Induced and Spontaneous Autoimmune Diabetes SO DIABETES LA English DT Article ID BETA-CELLS; NATURAL-HISTORY; TRANSGENIC MICE; FLOW-CYTOMETRY; MOUSE MODEL; B-CELLS; INSULIN; HYPOGLYCEMIA; GLUCAGON; ISLETS AB OBJECTIVE-Insulin deficiency in type 1 diabetes and in rodent autoimmune diabetes models is caused by beta-cell-specific killing by autoreactive T-cells. Less is known about beta-cell numbers and phenotype remaining at diabetes onset and the fate of other pancreatic endocrine cellular constituents. RESEARCH DESIGN AND METHODS-We applied multi-color flow cytometry, confocal microscopy, and immunohistochemistry, supported by quantitative RT-PCR, to simultaneously track pancreatic endocrine cell frequencies and phenotypes during a T-cell-mediated beta-cell-destructive process using two independent autoimmune diabetes models, an inducible autoantigen-specific model and the spontaneously diabetic NOD mouse. RESULTS-The proportion of pancreatic insulin-positive beta-cells to glucagon-positive alpha-cells was about 4:1 in nondiabetic mice. Islets isolated from newly diabetic mice exhibited the expected severe beta-cell depletion accompanied by phenotypic beta-cell changes (i.e., hypertrophy and degranulation), but they also revealed a substantial loss of alpha-cells, which was further confirmed by quantitative immunohistochemisty. While maintaining normal randomly timed serum glucagon levels, newly diabetic mice displayed an impaired glucagon secretory response to non-insulin-induced hypoglycemia. CONCLUSIONS-Systematically applying multi-color flow cytometry and immunohistochemistry to track declining beta-cell numbers in recently diabetic mice revealed an altered endocrine cell composition that is consistent with a prominent and unexpected islet alpha-cell loss. These alterations were observed in induced and spontaneous autoimmune diabetes models, became apparent at diabetes onset, and differed markedly within islets compared with sub-islet-sized endocrine cell clusters and among pancreatic lobes. We propose that these changes are adaptive in nature, possibly fueled by worsening glycemia and regenerative processes. Diabetes 58:1175-1184, 2009 C1 [Pechhold, Klaus; Zhu, Xiaolong; Harrison, Victor S.; Lee, Janet; Chakrabarty, Sagarika; Koczwara, Kerstin; Harlan, David M.] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Koczwara, Kerstin] Helmholtz Ctr, Res Grp Diabet, Diabet Res Inst, Munich, Germany. RP Pechhold, K (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM klausp@intra.niddk.nih.gov OI Harrison, Victor/0000-0003-3397-6045 FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 42 TC 19 Z9 19 U1 1 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2009 VL 58 IS 5 BP 1175 EP 1184 DI 10.2337/db08-0616 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440YX UT WOS:000265736700017 PM 19228810 ER PT J AU Nansel, TR Iannotti, RJ Simons-Morton, BG Plotnick, LP Clark, LM Zeitzoff, L AF Nansel, Tonja R. Iannotti, Ronald J. Simons-Morton, Bruce G. Plotnick, Leslie P. Clark, Loretta M. Zeitzoff, Linda TI Long-Term Maintenance of Treatment Outcomes: Diabetes Personal Trainer Intervention for Youth With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID METABOLIC-CONTROL; ADOLESCENTS; MELLITUS AB OBJECTIVE - To describe a 2-year follow-up of A1C outcomes of a self-regulation intervention for youth with type 1. diabetes. RESEARCH DESIGN AND METHODS - A total of 81 youths with type 1 diabetes ages 11-16 years were randomized to usual care versus a diabetes personal trainer intervention consisting of six self-monitoring, goal-setting, and problem-solving sessions with trained nonprofessionals. A1C data were obtained from medical records 2 years postintervention, and ANCOVA adjusting for age and baseline A1C was conducted. RESULTS - An overall intervention effect on A1C (8.93% control vs. 8.43% intervention; F = 8.24, P = 0,05) and a significant intervention-by-age interaction (F = 9.88; P = 0.002) were observed, indicating a greater effect among older than younger Youths. Subgroup analyses demonstrated no treatment group differences among pre-/early adolescents but a significant difference in A1C among middle adolescents (9.61% control vs. 8.46% intervention; F = 7.20, P = 0.011). CONCLUSIONS - Findings indicate maintenance of intervention effects on A1C observed at 1-year follow-up. C1 [Nansel, Tonja R.; Iannotti, Ronald J.; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Zeitzoff, Linda] Mt Washington Pediat Hosp, Baltimore, MD USA. [Plotnick, Leslie P.; Clark, Loretta M.] Johns Hopkins Med Ctr, Dept Pediat Endocrinol, Baltimore, MD USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX No potential conflicts of interest relevant to this article were reported. NR 10 TC 18 Z9 19 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 807 EP 809 DI 10.2337/dc08-1968 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800011 PM 19208916 ER PT J AU Jain, SH Massaro, JM Hoffmann, U Rosito, GA Vasan, RS Raji, A O'Donnell, CJ Meigs, JB Fox, CS AF Jain, Shilpa H. Massaro, Joseph M. Hoffmann, Udo Rosito, Guido A. Vasan, Ramachandran S. Raji, Annaswamy O'Donnell, Christopher J. Meigs, James B. Fox, Caroline S. TI Cross-Sectional Associations Between Abdominal and Thoracic Adipose Tissue Compartments and Adiponectin and Resistin in the Framingham Heart Study SO DIABETES CARE LA English DT Article; Proceedings Paper CT 68th Annual Meeting of the American-Diabetes-Association CY JUN 06-10, 2008 CL San Francisco, CA SP Amer Diabet Assoc ID BODY-FAT DISTRIBUTION; RISK-FACTORS; INSULIN SENSITIVITY; VISCERAL ADIPOSITY; GENE-EXPRESSION; METABOLIC RISK; OLDER-ADULTS; OBESITY; ADIPOCYTOKINES; CALCIFICATION AB OBJECTIVE- To test the association of regional fat depots with circulating adiponectin and resistin concentrations and to assess the potential mediating effect of adipokines on associations between abdominal fat depots and cardiometabolic risk factors. RESEARCH DESIGN AND METHODS- Participants from the Framingham Heart Study offspring cohort (n = 916, 55% women; mean age 59 years) free of cardiovascular disease underwent computed tomography measurement of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), pericardial fat, and intrathoracic fat, volumes and assays of circulating adiponectin and resistin. RESULTS- VAT, SAT, pericardial fat, and intrathoracic fat were negatively correlated with adiponectin (r = -0.19 to -0.34, P < 0.001 [women]; r = -0.15 to -0.26, P < 0.01 [men] except SAT) and positively correlated with resistin (r = 0.16-0.21, P < 0.001 [women]; r = 0.11-0.14, P < 0.05 [men] except VAT). VAT increased the multivariable model R(2) for adiponectin from 2-4% to 10-13% and for resistin from 3-4% to 3-6%. Adjustment for adipokines did not fully attenuate associations between VAT, SAT, and cardiometabolic risk factors. CONCLUSIONS- Adiponectin and resistin are correlated with fat depots cross-sectionally, but none of the adipokines can serve as surrogates for the fat depots. Relations between VAT SAT, and cardiometabolic risk factors were not fully explained by adiponectin or resistin concentrations. C1 [Jain, Shilpa H.; Raji, Annaswamy; Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Hoffmann, Udo; Rosito, Guido A.] Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA. [Rosito, Guido A.] Fed Fdn Sch Med Sci Porto Alegre, Porto Alegre, RS, Brazil. [Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Fox, CS (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, 75 Francis St, Boston, MA 02115 USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [N01HC25195, 2K24HL04334, K24 HL004334, N01-HC-25195, T32 HL007609]; NIDDK NIH HHS [K24 DK080140, R01 DK080739] NR 22 TC 27 Z9 28 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 903 EP 908 DI 10.2337/dc08-1733 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800032 PM 19223612 ER PT J AU Thearle, MS Bunt, JC Knowler, WC Krakoff, J AF Thearle, Marie S. Bunt, Joy C. Knowler, William C. Krakoff, Jonathan TI Childhood Predictors of Adult Acute Insulin Response and Insulin Action SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; X-RAY ABSORPTIOMETRY; PIMA-INDIANS; SECRETORY DYSFUNCTION; YOUNG ADULTHOOD; RESISTANCE; OBESITY; ADIPOSITY; LIFE; SUSCEPTIBILITY AB OBJECTIVE- Because declines in acute insulin response (AIR) and insulin action (M) predict development of type 2 diabetes, we sought to determine childhood factors that predict insulin action and AIR using longitudinal data from young Pima Indian adults with normal glucose regulation. RESEARCH DESIGN AND METHODS- Predictors of adult M, measured by the euglycemic-hyperinsulinemic clamp, and AIR, measured after a 25-g glucose bolus, were assessed in 76 individuals from a set of childhood data (BMI, systolic blood pressure [sBP] and diastolic blood pressure, cholesterol, fasting and 2-h insulin, and glucose levels during an oral glucose tolerance test). RESULTS- After adjustment for sex, adult percent body fat, adult and childhood age, childhood BMI, and sBP were negative and independent predictors of adult M. A 5 kg/m(2) increase in childhood BMI was associated with a 7.4% decrease in adult insulin action (95% Cl - 12.7 to -1.8%, P = 0.01) and a 10-mmHg increase in childhood sBP With a 5.0% decrease in adult M (95% Cl -8.4 to -1.4%, P = 0.007). After a similar adjustment with M as an additional covariate, childhood 2-h insulin was a positive predictor of adult AIR such that a 25% increase predicted a 7.3% increase in adult AIR (95% CI 1.5-13.5%, P = 0.014). CONCLUSIONS - Childhood insulin response during an oral glucose challenge predicts adult AIR, indicating that beta-cell capacity may be set early in life. Childhood measures related to adiposity predict adult insulin action, which may reflect common underlying mechanisms that may be amenable to modification through programs targeting prevention or treatment of childhood obesity. C1 [Thearle, Marie S.; Bunt, Joy C.; Knowler, William C.; Krakoff, Jonathan] NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA. RP Thearle, MS (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA. EM thearlem@mail.nih.gov FU Intramural NIH HHS NR 24 TC 9 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2009 VL 32 IS 5 BP 938 EP 943 DI 10.2337/dc08-1833 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444EG UT WOS:000265962800038 PM 19228868 ER PT J AU Gellar, L Rovner, AJ Nansel, TR AF Gellar, Lauren Rovner, Alisha J. Nansel, Tonja R. TI Whole Grain and Legume Acceptability Among Youths With Type 1 Diabetes SO DIABETES EDUCATOR LA English DT Article ID CORONARY-HEART-DISEASE; DIETARY FIBER; INSULIN SENSITIVITY; GLYCEMIC INDEX; RISK; CONSUMPTION; ADOLESCENTS; FOODS; PREVENTION; MELLITUS AB Purpose This pilot study investigated the acceptability of whole grain and legume foods in youths with type 1 diabetes and determined demographic and behavioral factors associated with their acceptability. Methods Youths with type 1 diabetes (7.0 to 16.9 years) were recruited during a diabetes camp and completed self-report measures of food acceptability, eating behaviors, and demographics. An overall acceptability score for whole grains and for legumes was calculated as the sum of foods in each category rated as either "tried and liked" or "not tried and willing to try." Correlations of whole grain and legume acceptability with demographic characteristics were examined. Results One hundred twenty-eight youths participated (70% females, mean age 11.6 +/- 2.3 years). Whole grain foods with the highest acceptability were corn bread (85% tried/liked and 11% willing to try) and whole wheat bread (72% tried/liked and 3% willing to try). Total whole grain acceptability was negatively associated with days per week of fast food consumption (r = -0.21; P < .02) and living in an urban environment (r = -0.24; P < .01). Chili with beans (66% tried/liked and 8% willing to try) and baked beans (57% tried/liked and 19% willing to try) were the legume-containing foods with the highest acceptability. There were no significant associations between demographic factors and total legume acceptability. Conclusions These findings demonstrate the variability in acceptability among whole grains and legumes in youths with type 1 diabetes and the importance of addressing acceptability when counseling youths or designing nutrition interventions to improve consumption of these foods. C1 [Gellar, Lauren] Univ Massachusetts, Sch Med, Clin & Populat Hlth Res Div, Worcester, MA 01605 USA. [Rovner, Alisha J.; Nansel, Tonja R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Gellar, L (reprint author), Univ Massachusetts, Sch Med, Clin & Populat Hlth Res Div, 55 Lake Ave, Worcester, MA 01605 USA. EM lauren.gellar@umassmed.edu OI Nansel, Tonja/0000-0002-8298-7595 FU Intramural Research Program of the National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 26 TC 6 Z9 6 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2009 VL 35 IS 3 BP 422 EP 427 DI 10.1177/0145721709333267 PG 6 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 448VF UT WOS:000266289400003 PM 19289543 ER PT J AU Stumvoll, M Bogardus, C AF Stumvoll, M. Bogardus, C. TI Glucose allostasis: Disrobing common wisdom SO DIABETOLOGIA LA English DT Editorial Material DE Allostasis; Disposition index; Insulin sensitivity; Insulin secretion C1 [Stumvoll, M.] Univ Leipzig, Dept Med, D-04301 Leipzig, Germany. [Bogardus, C.] NIDDK, Dept Hlth & Human Serv, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Stumvoll, M (reprint author), Univ Leipzig, Dept Med, Liebigstr 18, D-04301 Leipzig, Germany. EM michael.stumvoll@medizin.uni-leipzig.de NR 7 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2009 VL 52 IS 5 BP 779 EP 780 DI 10.1007/s00125-009-1310-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 428WZ UT WOS:000264884100006 PM 19266180 ER PT J AU Malkesman, O Austin, DR Chen, G Manji, HK AF Malkesman, Oz Austin, Daniel R. Chen, Guang Manji, Husseini K. TI Reverse translational strategies for developing animal models of bipolar disorder SO DISEASE MODELS & MECHANISMS LA English DT Review ID CELLULAR PLASTICITY CASCADES; GLYCOGEN-SYNTHASE KINASE-3; FAMILY-BASED ASSOCIATION; MITOCHONDRIAL DYSFUNCTION; GLUCOCORTICOID-RECEPTOR; MOOD STABILIZERS; LEARNED HELPLESSNESS; CANDIDATE GENES; CHROMOSOMES 6Q; PROTEIN BCL-2 AB Bipolar disorder (BD) affects a significant portion of the population of the world, yet there has been limited success in developing novel treatments for the disorder. One of the major reasons for this dearth is the absence of suitable animal models for BD. Traditionally, animal models of human phenomena have been evaluated based on similarity to the human syndrome, response to appropriately corresponding medications, and the degree to which a model supports a common mechanistic theory between the human disorder and the model itself. The following review emphasizes the use of 'reverse translation, drawing on patient-based findings to develop suitable animal models for BD. We highlight some examples of this strategy, emphasizing their construct validity as a starting point. These studies have produced informative models that have altered the expression of genes/pathways implicated in BD, including the point mutation D181A of mouse mitochondrial DNA polymerase (POLG), glutamate receptor 6 (GluR6), Clock, extracellular regulated kinase 1 (ERK1), glycogen synthase kinase-3 beta (GSK-3 beta), B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated athanogene (BAG-1). These studies demonstrate that this method is useful, viable and deserves attention in new efforts to generate animal models of BD. C1 [Malkesman, Oz; Austin, Daniel R.; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. EM manji@nih.gov RI Chen, Guang/A-2570-2017 FU Intramural Research Program at the National Institute of Mental Health (NIMH-NIH) FX Work in the authors' lab was supported by the Intramural Research Program at the National Institute of Mental Health (NIMH-NIH). loline Henter provided invaluable editorial assistance. NR 105 TC 33 Z9 34 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD MAY-JUN PY 2009 VL 2 IS 5-6 BP 238 EP 245 DI 10.1242/dmm.001628 PG 8 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 476PS UT WOS:000268455300010 PM 19407332 ER PT J AU Burgess, JP Green, JS Hill, JM Zhan, Q Lindeblad, M Lyubimov, A Kapetanovic, IM Schwartz, A Thomas, BF AF Burgess, Jason P. Green, Jonathan S. Hill, Judith M. Zhan, Qiao Lindeblad, Matthew Lyubimov, Alexander Kapetanovic, Izet M. Schwartz, Arthur Thomas, Brian F. TI Identification of [C-14]Fluasterone Metabolites in Urine and Feces Collected from Dogs after Subcutaneous and Oral Administration of [C-14]Fluasterone SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY NOV 11-15, 2007 CL San Diego, CA SP Amer Assoc Pharmaceut Scientists ID LONG-TERM TREATMENT; DEHYDROEPIANDROSTERONE DHEA; BREAST-CANCER; POSTMENOPAUSAL WOMEN; MICE; CHEMOPREVENTION; INHIBITION; RAT; TUMORIGENESIS; PREVENTION AB The objective of this research was the identification of the metabolic profile of fluasterone, a synthetic derivative of dehydroepiandrosterone, in dogs treated orally or subcutaneously with [4-C-14] fluasterone. Separation and characterization techniques used to identify the principal metabolites of fluasterone in urine and feces included high-performance liquid chromatography (HPLC), liquid scintillation spectrometry, HPLC/tandem mass spectrometry, and NMR. In urine, the majority of the radioactivity was present as two components that had apparent molecular weights consistent with their tentative identification as monoglucuronide conjugates of 4 alpha-hydroxy-16 alpha-fluoro-5-androsten-17 beta-ol and X(alpha or beta)-4 alpha-dihydroxy-16 alpha-fluoro-5-androsten-17 beta-ol. The identification of the monoglucuronide conjugate of 4 alpha-hydroxy-16 alpha-fluoro-5-androsten-17 beta-ol was also supported by NMR data. In support of this identification, these metabolites were cleaved with glucuronidase enzyme treatment, which gave rise to components with molecular weights again consistent with the aglycones of a monohydroxylated, 17-keto reduced (dihydroxy) fluasterone metabolite and a dihydroxylated, 17-keto reduced (trihydroxy) fluasterone metabolite. In feces, nonconjugated material predominated. The primary metabolites eliminated in feces were the two hydroxy fluasterone metabolites arising from 17-reduction (16 alpha-fluoro-5-androsten-17 beta-ol and 16 alpha-fluoro-5-androsten-17 alpha-ol) and 4 alpha-hydroxy-16 alpha-fluoro-5-androsten-17 beta-ol that was present in urine in glucuronide form. C1 [Burgess, Jason P.; Green, Jonathan S.; Hill, Judith M.; Zhan, Qiao; Thomas, Brian F.] RTI Int, Analyt Chem & Pharmaceut Grp, Res Triangle Pk, NC 27709 USA. [Kapetanovic, Izet M.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, NIH, Bethesda, MD USA. [Lindeblad, Matthew; Lyubimov, Alexander] Univ Illinois, Toxicol Res Lab, Chicago, IL USA. [Schwartz, Arthur] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. RP Thomas, BF (reprint author), RTI Int, Analyt Chem & Pharmaceut Grp, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM bft@rti.org OI Thomas, Brian/0000-0002-0097-4804 FU NCI NIH HHS [N01-CN-43306] NR 19 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAY PY 2009 VL 37 IS 5 BP 1089 EP 1097 DI 10.1124/dmd.108.023614 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 434JC UT WOS:000265270000020 PM 19196848 ER PT J AU Munge, BS Krause, CE Malhotra, R Patel, V Gutkind, JS Rusling, JF AF Munge, Bernard S. Krause, Colleen E. Malhotra, Ruchika Patel, Vyomesh Gutkind, J. Silvio Rusling, James F. TI Electrochemical immunosensors for interleukin-6. Comparison of carbon nanotube forest and gold nanoparticle platforms SO ELECTROCHEMISTRY COMMUNICATIONS LA English DT Article DE Electrochemical immunosensor; Cancer biomarker; Carbon nanotubes; Gold nanoparticles; Protein detection ID SURFACE-PLASMON RESONANCE; PROSTATE-SPECIFIC ANTIGEN; CANCER; LABELS; ASSAY; BIOMARKERS; CARCINOMA; DISEASE AB Electrochemical immunosensors based on single wall nanotube (SWNT) forests and 5 nm glutathione-protected gold nanoparticles (GSH-AuNP) were developed and compared for the measurement of human cancer biomarker interleukin-6 (IL-6) in serum. Detection was based on sandwich immunoassays using multiple (14-16) horseradish peroxidase labels conjugated to a secondary antibody. Performance was optimized by effective blocking of non-specific binding (NSB) of the labels using bovine serum albumin. The GSH-AuNP immunosensor gave a detection limit (DL) of 10 pg mL(-1) IL-6 (500 amol mL(-1)) in 10 mu L. calf serum, which was 3-fold better than 30 pg mL(-1) found for the SWNT forest immunosensor for the same assay protocol. The GSH-AuNPs platform also gave a Much larger linear dynamic range (20-4000 pg mL(-1)) than the SWNT system (40-150 pg mL(-1)), but the SWNTs had 2-fold better sensitivity in the low pg mL(-1) range. (C) 2009 Elsevier B.V. All rights reserved. C1 [Malhotra, Ruchika; Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. [Munge, Bernard S.; Krause, Colleen E.] Salve Regina Univ, Dept Chem, Newport, RI 02840 USA. [Patel, Vyomesh; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Rusling, James F.] Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. [Rusling, James F.] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 USA. [Rusling, James F.] Natl Univ Ireland Galway, Sch Chem, Galway, Ireland. RP Rusling, JF (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd,U-60, Storrs, CT 06269 USA. EM James.Rusling@uconn.edu RI Gutkind, J. Silvio/A-1053-2009 FU National Center for Research Resource (NCRR) [P20RR016457]; NIEHS/NIH [ES013557]; National Institute of Dental and Craniofacial Research, NIH; Science Foundation Ireland FX This research was supported by Grant No. P20RR016457 from the National Center for Research Resource (NCRR), a component of the US National Institute of Health (NIH), by Grant No. ES013557 from NIEHS/NIH, and by the intramural programs of the National Institute of Dental and Craniofacial Research, NIH. JFR is grateful to Science Foundation Ireland for a Walton Research Fellowship in 2008/2009. NR 28 TC 67 Z9 70 U1 2 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1388-2481 EI 1873-1902 J9 ELECTROCHEM COMMUN JI Electrochem. Commun. PD MAY PY 2009 VL 11 IS 5 BP 1009 EP 1012 DI 10.1016/j.elecom.2009.02.044 PG 4 WC Electrochemistry SC Electrochemistry GA 452KF UT WOS:000266538200020 PM 20046945 ER PT J AU Adelberg, DE Bishop, MR AF Adelberg, David E. Bishop, Michael R. TI Emergencies Related to Cancer Chemotherapy and Hematopoietic Stem Cell Transplantation SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Review DE Chemotherapy; Stem cell transplant; Neutropenia; Anemia; Cardiotoxicity; Graft-versus-host disease ID BONE-MARROW-TRANSPLANTATION; INTRATHECAL METHOTREXATE OVERDOSE; RANDOMIZED CONTROLLED-TRIALS; FEBRILE NEUTROPENIC PATIENTS; NON-HODGKINS-LYMPHOMA; VERSUS-HOST-DISEASE; DOUBLE-BLIND; RECEIVING CHEMOTHERAPY; VENOOCCLUSIVE DISEASE; PERIPHERAL NEUROPATHY AB As a vast majority of oncologic treatments are being administered in the outpatient setting, emergency department (ED) physicians are increasingly encountering patients who present with a wide array of toxicities that are a direct effect of chemotherapy. This review aims to highlight the most often encountered and clinically relevant toxicities of the more commonly administered chemotherapeutic drugs. In addition, because stem cell transplantation is being used increasingly for various malignancies, a brief introduction to post-transplant complications is included. C1 [Adelberg, David E.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Adelberg, DE (reprint author), NCI, Med Oncol Branch, 10 Ctr Dr,CRC Room 12N226, Bethesda, MD 20892 USA. EM adelbergd@mail.nih.gov NR 106 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8627 EI 1558-0539 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD MAY PY 2009 VL 27 IS 2 BP 311 EP + DI 10.1016/j.emc.2009.01.005 PG 22 WC Emergency Medicine SC Emergency Medicine GA 460SF UT WOS:000267206700012 PM 19447314 ER PT J AU Yang, ST Liu, AY Weidenhammer, A Cooksey, RC McClain, D Kim, MK Aguilera, G Abel, ED Chung, JH AF Yang, Shutong Liu, Aiyi Weidenhammer, Adam Cooksey, Robert C. McClain, Donald Kim, Myung K. Aguilera, Greti Abel, E. Dale Chung, Jay H. TI The Role of mPer2 Clock Gene in Glucocorticoid and Feeding Rhythms SO ENDOCRINOLOGY LA English DT Article ID NIGHT-EATING SYNDROME; CIRCADIAN CLOCK; FOOD-INTAKE; MELANOCORTIN-4 RECEPTOR; SUPRACHIASMATIC NUCLEI; FRAMESHIFT MUTATION; MESSENGER-RNA; OBESITY; LEPTIN; SLEEP AB The circadian clock synchronizes the activity level of an organism to the light-dark cycle of the environment. Energy intake, as well as energy metabolism, also has a diurnal rhythm. Although the role of the clock genes in the sleep-wake cycle is well characterized, their role in the generation of the metabolic rhythms is poorly understood. Here, we use mice deficient in the clock protein mPer2 to study how the circadian clock regulates two critical metabolic rhythms: glucocorticoid and food intake rhythms. Our findings indicate that mPer2-/- mice do not have a glucocorticoid rhythm even though the corticosterone response to hypoglycemia, ACTH, and restraint stress is intact. In addition, the diurnal feeding rhythm is absent in mPer2-/- mice. On high-fat diet, they eat as much during the light period as they do during the dark period and develop significant obesity. The diurnal rhythm of neuroendocrine peptide alpha MSH, a major effector of appetite control, is disrupted in the hypothalamus of mPer2-/- mice even though the diurnal rhythm of ACTH, the alpha MSH precursor, is intact. Peripheral injection of alpha MSH, which has been shown to enter the brain, restored the feeding rhythm and induced weight loss in mPer2-/- mice. These findings emphasize the requirement of mPer2 in appetite control during the inactive period and the potential role of peripherally administered alpha MSH in restoring night-day eating pattern in individuals with circadian eating disorders such as night-eating syndrome, which is also associated with obesity. (Endocrinology 150: 2153-2160, 2009) C1 [Yang, Shutong; Weidenhammer, Adam; Kim, Myung K.; Chung, Jay H.] NHLBI, Lab Biochem Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Aguilera, Greti] NICHHD, Dev Endocrinol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Natl Inst Hlth, Rockville, MD 20852 USA. [Cooksey, Robert C.; McClain, Donald; Abel, E. Dale] Univ Utah, Sch Med, Program Human Mol Biol & Genet, Div Endocrinol Diabet & Metab, Salt Lake City, UT 84112 USA. RP Chung, JH (reprint author), NHLBI, Lab Biochem Genet, Natl Inst Hlth, Bldg 10-7D14,10 Ctr Dr, Bethesda, MD 20892 USA. EM chungj@nhlbi.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Intramural Research Program; National Heart Lung and Blood Institute; National Institutes of Health FX This work was supported by the Intramural Research Program, National Heart Lung and Blood Institute, National Institutes of Health. NR 46 TC 104 Z9 107 U1 1 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2009 VL 150 IS 5 BP 2153 EP 2160 DI 10.1210/en.2008-0705 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436IQ UT WOS:000265407500017 PM 19179447 ER PT J AU Nierth-Simpson, EN Martin, MM Chiang, TC Melnik, LI Rhodes, LV Muir, SE Burow, ME McLachlan, JA AF Nierth-Simpson, Erica N. Martin, Melvenia M. Chiang, Tung-Chin Melnik, Lilia I. Rhodes, Lyndsay V. Muir, Shannon E. Burow, Matthew E. McLachlan, John A. TI Human Uterine Smooth Muscle and Leiomyoma Cells Differ in Their Rapid 17 beta-Estradiol Signaling: Implications for Proliferation SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; ESTROGEN-RECEPTOR-ALPHA; GROWTH-FACTOR-I; HUMAN MYOMETRIAL CELLS; IGF-I; DIETHYLSTILBESTROL DES; REPRODUCTIVE FACTORS; STIMULATED GROWTH; GENE-EXPRESSION; GENOMIC ACTIONS AB Uterine leiomyomas, benign uterine smooth muscle tumors that affect 30% of reproductive-aged women, are a significant health concern. The initiation event for these tumors is unclear, but 17 beta-estradiol (E2) is an established promoter of leiomyoma growth. E2 not only alters transcription of E2-regulated genes but also can rapidly activate signaling pathways. The aim of our study is to investigate the role of rapid E2-activated cytoplasmic signaling events in the promotion of leiomyomas. Western blot analysis revealed that E2 rapidly increases levels of phosphorylated protein kinase C alpha (PKC alpha) in both immortalized uterine smooth muscle (UtSM) and leiomyoma (UtLM) cell lines, but increases levels of phosphorylated ERK1/2 only in UtLM cells. Our studies demonstrate a paradoxical effect of molecular and pharmacological inhibition of PKC alpha on ERK1/2 activation and cellular proliferation in UtLM and UtSM cells. PKC alpha inhibition decreases levels of phosphorylated ERK1/2 and proliferation in UtLM cells but raises these levels in UtSM cells. cAMP-PKA signaling is rapidly activated only in UtSM cells with E2 and inhibits ERK1/2 activation and proliferation. We therefore propose a model whereby E2's rapid activation of PKC alpha and cAMP-PKA signaling plays a central role in the maintenance of a low proliferative index in normal uterine smooth muscle via its inhibition of the MAPK cascade and these pathways are altered in leiomyomas to promote MAPK activation and proliferation. These studies demonstrate that rapid E2-signaling pathways contribute to the promotion of leiomyomas. (Endocrinology 150: 2436-2445, 2009) C1 [McLachlan, John A.] Tulane Univ, Tulane Med Sch, Ctr Bioenvironm Res, New Orleans, LA 70118 USA. [Nierth-Simpson, Erica N.; Burow, Matthew E.; McLachlan, John A.] Tulane Med Sch, Tulane Canc Ctr, New Orleans, LA 70112 USA. [Melnik, Lilia I.] Tulane Med Sch, Dept Microbiol, New Orleans, LA 70112 USA. [Burow, Matthew E.; McLachlan, John A.] Tulane Med Sch, Dept Pharmacol, New Orleans, LA 70112 USA. [Rhodes, Lyndsay V.; Muir, Shannon E.; Burow, Matthew E.] Tulane Med Sch, Dept Med, Sect Hematol & Med Oncol, New Orleans, LA 70112 USA. [Martin, Melvenia M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP McLachlan, JA (reprint author), Tulane Univ, Tulane Med Sch, Ctr Bioenvironm Res, New Orleans, LA 70118 USA. EM jmclach@tulane.edu RI Burow, Matthew/D-6351-2013 OI Burow, Matthew/0000-0002-0642-6630 FU Office of Naval Research [N000140611136]; National Institutes of Health [DK059389]; Louisiana Cancer Research Consortium FX This work was supported by Grant N000140611136 from the Office of Naval Research, Grant DK059389 from the National Institutes of Health, and a postdoctoral fellowship from the Louisiana Cancer Research Consortium. NR 96 TC 21 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2009 VL 150 IS 5 BP 2436 EP 2445 DI 10.1210/en.2008-0224 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436IQ UT WOS:000265407500052 PM 19179429 ER PT J AU Shen, M Vermeulen, R Rajaraman, P Menashe, I He, XZ Chapman, RS Yeager, M Thomas, G Burdett, L Hutchinson, A Yuenger, J Chanock, S Lan, Q AF Shen, Min Vermeulen, Roel Rajaraman, Preetha Menashe, Idan He, Xingzhou Chapman, Robert S. Yeager, Meredith Thomas, Gilles Burdett, Laurie Hutchinson, Amy Yuenger, Jeff Chanock, Stephen Lan, Qing TI Polymorphisms in Innate Immunity Genes and Lung Cancer Risk in Xuanwei, China SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE lung cancer; innate immunity; single nucleotide polymorphism; polycyclic aromatic hydrocarbon; coal; FERC2; KLK ID HUMAN TISSUE; KALLIKREIN; ASSOCIATION; EXPRESSION; INFLAMMATION; FAMILY; FCER2; CELLS; SERUM; KLK15 AB The high incidence of lung cancer in Xuanwei County, China has been attributed to exposure to indoor smoky coal emissions that contain polycyclic aromatic hydrocarbons (PAHs). The inflammatory response induced by coal smoke components may promote lung tumor development. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung cancer risk in a population-based case-control study (122 cases and 122 controls) in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% Cl: 0.16-0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk globally (false discovery rate value < 0.15). In addition, there were positive interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P(interaction) = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P(interaction) = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes may play a role in the genesis of lung cancer caused by PAH-containing coal smoke. Integrin/receptor and complement pathways as well as IgE regulation are particularly noteworthy. Environ. Mol. Mutagen. 50:285-290, 2009. (C) Published 2009 Wiley-Liss, Inc. C1 [Shen, Min; Rajaraman, Preetha; Menashe, Idan; Yeager, Meredith; Thomas, Gilles; Burdett, Laurie; Hutchinson, Amy; Yuenger, Jeff; Chanock, Stephen; Lan, Qing] NCI, NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet,DHHS, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. [Vermeulen, Roel] Univ Med Ctr Utrecht, Julius Ctr, Inst Risk Assessment Sci, Utrecht, Netherlands. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Inst Environm Hlth, Beijing, Peoples R China. [Chapman, Robert S.] Chulalongkorn Univ, Coll Publ Hlth Sci, Bangkok, Thailand. RP Shen, M (reprint author), NCI, NIH, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet,DHHS, Bethesda, MD 20892 USA. EM shenmi@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Chinese Center for Disease Control and Prevention; National Institutes of Health (NIH), National Cancer Institute FX Grant sponsors: Chinese Center for Disease Control and Prevention, the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. NR 32 TC 14 Z9 16 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAY PY 2009 VL 50 IS 4 BP 285 EP 290 DI 10.1002/em.20452 PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 432ZF UT WOS:000265172200002 PM 19170196 ER PT J AU Stout, MD Herbert, RA Kissling, GE Collins, BJ Travlos, GS Witt, KL Melnick, RL Abdo, KM Malarkey, DE Hooth, MJ AF Stout, Matthew D. Herbert, Ronald A. Kissling, Grace E. Collins, Bradley J. Travlos, Gregory S. Witt, Kristine L. Melnick, Ronald L. Abdo, Karnal M. Malarkey, David E. Hooth, Michelle J. TI Hexavalent Chromium Is Carcinogenic to F344/N Rats and B6C3F1 Mice after Chronic Oral Exposure SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE anemia; cancer; hexavalent chromium; histiocytic cellular infiltration; National Toxicology Program; oral cavity; small intestine ID DRINKING-WATER; DNA ADDUCTS; DOSE LEVELS; TOXICITY; MUTAGENICITY; ABSORPTION; MECHANISMS; INGESTION; MORTALITY; ASCORBATE AB BACKGROUND: Hexavalent chromium [Cr(VI)] is a human carcinogen after inhalation exposure. Humans also ingest Cr(VI) from contaminated drinking water and soil; however, limited data exist on the oral toxicity and carcinogenicity of Cr(VI). OBJECTIVE: We characterized the chronic oral toxicity and carcinogenicity of Cr(VI) in rodents. METHODS: The National Toxicology Program (NTP) conducted 2-year drinking water studies of Cr(VI) (as sodium dichromate dihydrate) in male and female F344/N rats and B6C3F1 mice. RESULTS: Cr(VI) exposure resulted in increased incidences of rare neoplasms of the squamous epithelium that lines the oral cavity (oral mucosa and tongue) in male and female rats, and of the epithelium lining the small intestine in male and female mice. Cr(VI) exposure did not affect survival but resulted in reduced mean body weights and water consumption, due at least in part to poor palatability of the dosed water. Cr(VI) exposure resulted in transient microcytic hypochromic anemia in rats and microcytosis in mice. Nonneoplastic lesions included diffuse epithelial hyperplasia in the duodenum and jejunum of mice and histiocytic cell infiltration in the duodenum, liver, and mesenteric and pancreatic lymph nodes of rats and mice. CONCLUSIONS: Cr(VI) was carcinogenic after administration in drinking water to male and female rats and mice. C1 [Stout, Matthew D.; Herbert, Ronald A.; Kissling, Grace E.; Collins, Bradley J.; Travlos, Gregory S.; Witt, Kristine L.; Melnick, Ronald L.; Abdo, Karnal M.; Malarkey, David E.; Hooth, Michelle J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Stout, MD (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. FU FDA HHS [1 Z01 ES045004-11 BB]; Intramural NIH HHS; NIEHS NIH HHS [Z01 ES045004] NR 51 TC 78 Z9 86 U1 1 U2 14 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2009 VL 117 IS 5 BP 716 EP 722 DI 10.1289/ehp.0800208 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 440SZ UT WOS:000265721300022 PM 19479012 ER PT J AU Ostroumova, E Brenner, A Oliynyk, V McConnell, R Robbins, J Terekhova, G Zablotska, L Likhtarev, I Bouville, A Shpak, V Markov, V Masnyk, I Ron, E Tronko, M Hatch, M AF Ostroumova, Evgenia Brenner, Alina Oliynyk, Valery McConnell, Robert Robbins, Jacob Terekhova, Galina Zablotska, Lydia Likhtarev, Ilya Bouville, Andre Shpak, Viktor Markov, Valentin Masnyk, Ihor Ron, Elaine Tronko, Mykola Hatch, Maureen TI Subclinical Hypothyroidism after Radioiodine Exposure: Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident (1998-2000) SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE Chernobyl nuclear accident; Chornobyl; dose-response relationship; hypothyroidism; ionizing radiation ID ATOMIC-BOMB SURVIVORS; SURVEY NHANES-III; IODINE DEFICIENCY; AUTOIMMUNE-THYROIDITIS; NATIONAL-HEALTH; SERUM-TSH; FOLLOW-UP; TEST-SITE; POPULATION; CHILDREN AB BAcKGROUND: Hypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (I-131). Data on risk of hypothyroidism from low to moderate I-131 thyroid doses are limited and inconsistent. OBJECTIVE: This study was conducted to quantify the risk of hypothyroidism prevalence in relation to I-131 doses received because of the Chornobyl accident. METHODS: This is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals < 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum. RESULTS: Mean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean I-131 thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH > 4 mIU/L, including 14 with overt hypothyroidism. We found a significant, small association between I-131 thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO <= 60 U/mL compared with individuals with ATPO > 60 U/mL (p < 0.001). CONCLUSIONS: This is the first study to find a significant relationship between prevalence of hypothyroidism and individual I-131 thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies. C1 [Ostroumova, Evgenia; Brenner, Alina; Bouville, Andre; Masnyk, Ihor; Ron, Elaine; Hatch, Maureen] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Oliynyk, Valery; Terekhova, Galina; Shpak, Viktor; Markov, Valentin; Tronko, Mykola] Inst Endocrinol & Metab, Kiev, Ukraine. [McConnell, Robert] Columbia Univ, Coll Phys & Surg, Thyroid Clin, Dept Med, New York, NY USA. [Robbins, Jacob] NIDDK, Clin Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Zablotska, Lydia] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Likhtarev, Ilya] Ukraine Acad Med Sci, Sci Ctr Radiat Med, Kiev, Ukraine. RP Brenner, A (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MS 7238,6120 Execut Blvd, Bethesda, MD 20892 USA. EM brennera@mail.nih.gov FU Intramural Research Program of the U.S. National Institutes of Health; U.S. National Cancer Institute; U.S. Department of Energy; The U.S. Nuclear Regulatory Commission FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, the U.S. National Cancer Institute, and the U.S. Department of Energy. The U.S. Nuclear Regulatory Commission provided the initial funds for purchase of equipment. NR 52 TC 14 Z9 14 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2009 VL 117 IS 5 BP 745 EP 750 DI 10.1289/ehp.0800184 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 440SZ UT WOS:000265721300026 PM 19479016 ER PT J AU Thorne, PS Cohn, RD Mav, D Arbes, SJ Zeldin, DC AF Thorne, Peter S. Cohn, Richard D. Mav, Deepak Arbes, Samuel J., Jr. Zeldin, Darryl C. TI Predictors of Endotoxin Levels in US Housing SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergens; asthma triggers; endotoxin; house dust; housing characteristics; indoor air; lipopolysaccharide; microorganism-associated molecular pattern; predictive model; reservoir dust ID 1ST NATIONAL-SURVEY; ALTERNARIA-ALTERNATA; DUST ENDOTOXIN; EXPOSURE RISK; GERMAN HOMES; BIRTH COHORT; ALLERGENS; ASTHMA; LEAD; PREVALENCE AB The relationship of domestic endotoxin exposure to allergy and asthma has been widely investigated. However, few studies have evaluated predictors of household endotoxin, and none have done so for multiple locations within homes and on a national scale. OBJECTIVES: We assayed 2,552 house dust samples in a nationwide study to understand the predictors of household endotoxin in bedroom floors, family room floors, beds, kitchen floors, and family room sofas. METHODS: Reservoir house dust from five locations within homes was assayed for endotoxin and demographic and housing information was assessed through questionnaire and onsite evaluation of 2,456 residents of 831 homes selected to represent national demographics. We performed repeated-measures analysis of variance (rANOVA) for 37 candidate variables to identify independent predictors of endotoxin. Meteorologic data were obtained for each primary sampling unit and tested as predictors of indoor endotoxin to determine if wetter or warmer microclimates were associated with higher endotoxin levels. RESULTS: Weighted geometric mean endotoxin concentration ranged from 18.7 to 80.5 endotoxin units (EU)/mg for the five sampling locations, and endotoxin load ranged from 4,160 to 19,500 EU/m(2). Bivariate analyses and rANOVA demonstrated that major predictors of endotoxin concentration were sampling location in the home, census division, educational attainment, presence of children, current dog ownership, resident-described problems with cockroaches, food debris, cockroach stains, and evidence of smoking observed by field staff. Low household income entered the model if educational attainment was removed. CONCLUSION: Increased endotoxin in household reservoir dust is principally associated with poverty, people, pets, household cleanliness, and geography. C1 [Thorne, Peter S.] Univ Iowa, Coll Publ Hlth, Dept Occupat & Environm Hlth, Environm Hlth Sci Res Ctr, Iowa City, IA 52242 USA. [Cohn, Richard D.; Mav, Deepak] Constella Grp LLC, Durham, NC USA. [Arbes, Samuel J., Jr.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC USA. RP Thorne, PS (reprint author), Univ Iowa, Coll Publ Hlth, Dept Occupat & Environm Hlth, Environm Hlth Sci Res Ctr, 100 Oakdale Campus,176 IREH, Iowa City, IA 52242 USA. EM peter-thorne@uiowa.edu FU National Institute of Environmental Health Sciences (NIEHS) [P30 ES05605]; U.S. Department of Housing and Urban Development's Office of Healthy Homes and Lead Hazard Control; Intramural Research Program of the NIEHS, National Institutes of Health FX This work was supported by National Institute of Environmental Health Sciences (NIEHS) grant P30 ES05605, U.S. Department of Housing and Urban Development's Office of Healthy Homes and Lead Hazard Control, and the Intramural Research Program of the NIEHS, National Institutes of Health. NR 23 TC 61 Z9 61 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2009 VL 117 IS 5 BP 763 EP 771 DI 10.1289/ehp.11759 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 440SZ UT WOS:000265721300029 PM 19479019 ER PT J AU Wacholder, S AF Wacholder, Sholom TI Bias in Full Cohort and Nested Case-Control Studies? SO EPIDEMIOLOGY LA English DT Editorial Material ID EXPOSURE; CANCER C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Wacholds@mail.nih.gov FU Intramural NIH HHS [Z01 CP010181-05] NR 6 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2009 VL 20 IS 3 BP 339 EP 340 DI 10.1097/EDE.0b013e31819ec966 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 433JJ UT WOS:000265199800005 PM 19289961 ER PT J AU Larsson, SC Mannisto, S Virtanen, MJ Kontto, J Albanes, D Virtamo, J AF Larsson, Susanna C. Mannisto, Satu Virtanen, Mikko J. Kontto, Jukka Albanes, Demetrius Virtamo, Jarmo TI Dairy Foods and Risk of Stroke SO EPIDEMIOLOGY LA English DT Article ID CONJUGATED LINOLEIC-ACID; METABOLIC SYNDROME; BODY-FAT; PLASMA-LIPOPROTEINS; ISCHEMIC-STROKE; BLOOD-PRESSURE; HEART-DISEASE; CONSUMPTION; MILK; SUPPLEMENTATION AB Background: Consumption of milk and other dairy foods has been associated with reduced risk of stroke, although not all studies have shown this consistently. Methods: We examined the association between dairy food intake and risk of stroke subtypes within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Between 1985 and 1988, 26,556 Finnish male smokers aged 50-69 years who had no history of stroke completed a food frequency questionnaire. We used Cox proportional hazards models to estimate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for potential confounders. Results: During a mean follow-up of 13.6 years, 2702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages were ascertained. We observed positive associations between whole milk intake and risk of intracerebral hemorrhage (RR = 1.41 for the highest vs. lowest quintile of intake; 95% CI = 1.02-1.96) and between yogurt intake and subarachnoid hemorrhage (RR = 1.83 for the highest vs. lowest quintile of intake; 95% CI = 1.20-2.80). Men in the highest quintile of cream intake had a moderate decreased risk of cerebral infarction (0.81; 0.72-0.92) and intracerebral hemorrhage (0.72; 0.52-1.00). There were no strong associations between intakes of total dairy, low-fat milk, sour milk, cheese, ice cream, or butter and risk of any stroke subtype. Conclusions: Theses findings suggest that intake of certain dairy foods may be associated with risk of stroke. C1 [Larsson, Susanna C.] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden. [Mannisto, Satu; Virtanen, Mikko J.; Kontto, Jukka; Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. [Albanes, Demetrius] NCI, NIH, Bethesda, MD 20892 USA. RP Larsson, SC (reprint author), Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, SE-17177 Stockholm, Sweden. EM susanna.larsson@ki.se RI Albanes, Demetrius/B-9749-2015; Larsson, Susanna/F-6065-2015; OI Larsson, Susanna/0000-0003-0118-0341; Mannisto, Satu/0000-0002-8668-3046; Kontto, Jukka/0000-0003-3899-9852 FU US National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda [N01-CN45165, N01-RC-45035, N01-RC-37004]; Swedish Council for Working Life and Social Research FX The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by Public Health Service contracts N01-CN45165, N01-RC-45035 and N01-RC-37004 from the US National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD. Susanna Larsson's research at the National Public Health Institute in Helsinki, Finland, was supported by a grant from the Swedish Council for Working Life and Social Research. NR 27 TC 37 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2009 VL 20 IS 3 BP 355 EP 360 DI 10.1097/EDE.0b013e3181935dd5 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 433JJ UT WOS:000265199800009 PM 19057387 ER PT J AU Lewis, DR Wade, TJ Lobdell, DT Neas, LM AF Lewis, Denise Riedel Wade, Timothy J. Lobdell, Danelle T. Neas, Lucas M. TI Rebecca Lea Calderon, 1955-2008 SO EPIDEMIOLOGY LA English DT Biographical-Item C1 [Lewis, Denise Riedel] NCI, Surveillance Res Program, Bethesda, MD 20892 USA. [Wade, Timothy J.; Lobdell, Danelle T.; Neas, Lucas M.] US EPA, Natl Hlth & Environm Effects Res Lab, Chapel Hill, NC USA. RP Lewis, DR (reprint author), NCI, Surveillance Res Program, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. EM lewisde@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2009 VL 20 IS 3 BP 461 EP 461 DI 10.1097/EDE.0b013e31819f2de9 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 433JJ UT WOS:000265199800025 ER PT J AU Shamim, S Hasler, G Liew, C Sato, S Theodore, WH AF Shamim, Sadat Hasler, Gregor Liew, Clarissa Sato, Susumu Theodore, William H. TI Temporal lobe epilepsy, depression, and hippocampal volume SO EPILEPSIA LA English DT Article DE Epilepsy; Temporal lobe; Depression; Comorbidity; Hippocampus; SCID; BDI ID COMPLEX PARTIAL SEIZURES; MAJOR DEPRESSION; SCLEROSIS; SURGERY; METABOLISM; COMORBIDITY; IMPAIRMENT; MORBIDITY; DISORDER; ATROPHY AB To evaluate the relationship between hippocampal volume loss, depression, and epilepsy. There is a significantly increased incidence of depression and suicide in patients with epilepsy. Both epilepsy and depression are associated with reduced hippocampal volumes, but it is uncertain whether patients with both conditions have greater atrophy than those with epilepsy alone. Previous studies used depression measures strongly weighted to current state, and did not necessarily assess the influence of chronic major depressive disorder ("trait"), which could have a greater impact on hippocampal volume. Fifty-five epilepsy patients with complex partial seizures (CPS) confirmed by electroencephalography (EEG) had three-dimensional (3D)-spoiled gradient recall (SPGR) acquisition magnetic resonance imaging (MRI) scans for hippocampal volumetric analysis. Depression screening was performed with the Beck Depression Inventory (BDI, 51 patients) and with the structured clinical inventory for DSM-IV (SCID, 34 patients). For the BDI, a score above 10 was considered mild to moderate, above 20 moderate to severe, and above 30 severe depression. MRI and clinical analysis were performed blinded to other data. Statistical analysis was performed with Systat using Student's t test and analysis of variance (ANOVA). There was a significant interaction between depression detected on SCID, side of focus, and left hippocampal volume. Patients with a diagnosis of depression and a right temporal seizure focus had significantly lower left hippocampal volume. A similar trend for an effect of depression on right hippocampal volume in patients with a right temporal focus did not reach statistical significance. Our results suggest that patients with right temporal lobe epilepsy and depression have hippocampal atrophy that cannot be explained by epilepsy alone. C1 [Shamim, Sadat; Sato, Susumu] NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. [Hasler, Gregor] NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Liew, Clarissa; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, EEG Sect, NIH, Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Division of Intramural Research, National Institutes of Neurological Disorders and Stroke FX W.H. Theodore owns General Electric stock. None of the other authors reports any conflict of interest. NR 35 TC 32 Z9 33 U1 4 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1067 EP 1071 DI 10.1111/j.1528-1167.2008.01883.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000013 PM 19054394 ER PT J AU Harden, CL Meador, KJ Pennell, PB Hauser, WA Gronseth, GS French, JA Wiebe, S Thurman, D Koppel, BS Kaplan, PW Robinson, JN Hopp, J Ting, TY Gidal, B Hovinga, CA Wilner, AN Vazquez, B Holmes, L Krumholz, A Finnell, R Hirtz, D Le Guen, C AF Harden, Cynthia L. Meador, Kimford J. Pennell, Page B. Hauser, W. Allen Gronseth, Gary S. French, Jacqueline A. Wiebe, Samuel Thurman, David Koppel, Barbara S. Kaplan, PeterW. Robinson, Julian N. Hopp, Jennifer Ting, Tricia Y. Gidal, Barry Hovinga, Collin A. Wilner, Andrew N. Vazquez, Blanca Holmes, Lewis Krumholz, Allan Finnell, Richard Hirtz, Deborah Le Guen, Claire TI Management issues for women with epilepsy-Focus on pregnancy (an evidence-based review): II. Teratogenesis and perinatal outcomes SO EPILEPSIA LA English DT Article DE Guideline; Pregnancy; Epilepsy; Antiepileptic drugs; Teratogenesis; Major congenital malformations; Apgar score; Small for gestational age ID ANTIEPILEPTIC DRUGS; IN-UTERO; MATERNAL EPILEPSY; CONGENITAL-MALFORMATIONS; PSYCHOMOTOR DEVELOPMENT; ANTICONVULSANT DRUGS; PRENATAL EXPOSURE; CHILDREN; VALPROATE; INTELLIGENCE AB A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of < 7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes. C1 [Harden, Cynthia L.] Univ Miami, Miami, FL USA. [Meador, Kimford J.; Pennell, Page B.] Emory Univ, Atlanta, GA 30322 USA. [Hauser, W. Allen] Columbia Univ, New York, NY USA. [Gronseth, Gary S.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [French, Jacqueline A.] NYU, Sch Med, New York, NY USA. [Wiebe, Samuel] Univ Calgary, Calgary, AB, Canada. [Thurman, David] Ctr Dis Control & Prevent, Atlanta, GA USA. [Koppel, Barbara S.] New York Med Coll, New York, NY USA. [Kaplan, PeterW.] Johns Hopkins Univ, Baltimore, MD USA. [Robinson, Julian N.; Holmes, Lewis] Harvard Univ, Sch Med, Boston, MA USA. [Hopp, Jennifer; Ting, Tricia Y.; Krumholz, Allan] Univ Maryland, Baltimore, MD 21201 USA. [Gidal, Barry] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. [Gidal, Barry] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Finnell, Richard] Texas A&M Univ, Hlth Sci Ctr, Houston, TX USA. [Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA. [Le Guen, Claire] Univ Penn, Philadelphia, PA 19104 USA. RP Harden, CL (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA. EM guidelines@aan.com RI French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU The Milken Family Foundation FX Ms. Le Guen reports no disclosures. NR 45 TC 104 Z9 108 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1237 EP 1246 DI 10.1111/j.1528-1167.2009.02129.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000034 PM 19507301 ER PT J AU Burneo, JG Del Brutto, O Delgado-Escueta, AV Gonzalez, AE Medina, MT Montano, SM Moyano, LM Nash, T Roman, G Singh, G White, AC Wiebe, S Garcia, HH AF Burneo, Jorge G. Del Brutto, Oscar Delgado-Escueta, Antonio V. Gonzalez, Armando E. Medina, Marco T. Montano, Silvia M. Moyano, Luz M. Nash, Theodore Roman, Gustavo Singh, Gagandeep White, A. Clinton, Jr. Wiebe, Samuel Garcia, Hector H. TI Workshop Report: Developing an international collaborative research network in neurocysticercosis and epilepsy SO EPILEPSIA LA English DT Editorial Material C1 [Burneo, Jorge G.] Univ Western Ontario, Epilepsy Programme, London, ON, Canada. [Del Brutto, Oscar] Hosp Clin Kennedy, Guayaquil, Ecuador. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Epilepsy Ctr Excellence, VA Greater Healthcare Syst, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru. [Gonzalez, Armando E.; Moyano, Luz M.; Garcia, Hector H.] Cysticercosis Eliminat Project, Tumbes, Peru. [Gonzalez, Armando E.; Garcia, Hector H.] Inst Peruano Parasitol Clin & Expt, Lima, Peru. [Medina, Marco T.] Univ Autonoma Honduras, Tegucigalpa, Honduras. [Montano, Silvia M.] US Naval Res Detachment, Lima, Peru. [Moyano, Luz M.; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Lima, Peru. [Nash, Theodore] Natl Inst Hlth, Bethesda, MD USA. [Roman, Gustavo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Singh, Gagandeep] Dayanand Med Coll, Ludhiana, Punjab, India. [White, A. Clinton, Jr.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Wiebe, Samuel] Univ Calgary, Dept Neurosci, Calgary, AB, Canada. [Garcia, Hector H.] Inst Ciencias Neurol, Dept Transmissible Dis, Lima, Peru. RP Burneo, JG (reprint author), Univ Western Ontario, Epilepsy Programme, London, ON, Canada. EM jburneo2@uwo.ca OI White, A Clinton/0000-0002-9668-4632; Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU Intramural NIH HHS [ZIA AI000846-15] NR 7 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1289 EP 1290 DI 10.1111/j.1528-1167.2008.01912.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000043 PM 19496808 ER PT J AU Burneo, JG Del Brutto, O Delgado-Escueta, AV Gonzalez, AE Medina, MT Montano, SM Moyano, LM Nash, T Roman, G Singh, G White, AC Wiebe, S Garcia, HH AF Burneo, Jorge G. Del Brutto, Oscar Delgado-Escueta, Antonio V. Gonzalez, Armando E. Medina, Marco T. Montano, Silvia M. Moyano, Luz M. Nash, Theodore Roman, Gustavo Singh, Gagandeep White, A. Clinton, Jr. Wiebe, Samuel Garcia, Hector H. TI Benign myoclonus of early infancy or Fejerman syndrome SO EPILEPSIA LA English DT Editorial Material ID SPASMS C1 [Burneo, Jorge G.] Univ Western Ontario, Epilepsy Programme, London, ON, Canada. [Del Brutto, Oscar] Hosp Clin Kennedy, Guayaquil, Ecuador. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, Epilepsy Ctr Excellence, VA Greater Healthcare Syst, Los Angeles, CA USA. [Delgado-Escueta, Antonio V.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Sch Vet Med, Lima 14, Peru. [Gonzalez, Armando E.; Moyano, Luz M.; Garcia, Hector H.] Cysticercosis Eliminat Project, Tumbes, Peru. [Gonzalez, Armando E.; Garcia, Hector H.] Inst Peruano Parasitol Clin & Expt, Lima, Peru. [Medina, Marco T.] Univ Autonoma Honduras, Tegucigalpa, Honduras. [Montano, Silvia M.] US Naval Res Detachment, Lima, Peru. [Moyano, Luz M.; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Lima, Peru. [Nash, Theodore] Natl Inst Hlth, Bethesda, MD USA. [Roman, Gustavo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Singh, Gagandeep] Dayanand Med Coll, Ludhiana, Punjab, India. [White, A. Clinton, Jr.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Wiebe, Samuel] Univ Calgary, Dept Neurosci, Calgary, AB, Canada. [Garcia, Hector H.] Inst Ciencias Neurol, Dept Transmissible Dis, Lima, Peru. RP Burneo, JG (reprint author), Univ Western Ontario, Epilepsy Programme, London, ON, Canada. EM jburneo2@uwo.ca NR 16 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2009 VL 50 IS 5 BP 1290 EP 1292 DI 10.1111/j.1528-1167.2009.02154.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 441LG UT WOS:000265770000044 ER PT J AU Taylor, J Nabel, E AF Taylor, Jennifer Nabel, Elizabeth TI Portrait statements of the International Associate Editors of the European Heart Journal SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 [Nabel, Elizabeth] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2009 VL 30 IS 10 BP 1155 EP 1156 DI 10.1093/eurheartj/ehp150 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446IL UT WOS:000266115200001 ER PT J AU Doucette, L Merner, ND Cooke, S Ives, E Galutira, D Walsh, V Walsh, T MacLaren, L Cater, T Fernandez, B Green, JS Wilcox, ER Shotland, L Li, XC Lee, M King, MC Young, TL AF Doucette, Lance Merner, Nancy D. Cooke, Sandra Ives, Elizabeth Galutira, Dante Walsh, Vanessa Walsh, Tom MacLaren, Linda Cater, Tracey Fernandez, Bridget Green, Jane S. Wilcox, Edward R. Shotland, Larry Li, X. C. Lee, Ming King, Mary-Claire Young, Terry-Lynn TI Profound, prelingual nonsyndromic deafness maps to chromosome 10q21 and is caused by a novel missense mutation in the Usher syndrome type IF gene PCDH15 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE PCDH15; isolated deafness; usher syndrome type IF; hypomorphic alleles ID BARDET-BIEDL-SYNDROME; SENSORY HAIR-CELLS; SYNDROME TYPE 1F; RECESSIVE DEAFNESS; HEARING-LOSS; NEWFOUNDLAND POPULATION; COCHLEAR IMPLANTATION; OUTPORT NEWFOUNDLAND; PROTOCADHERIN GENE; ALLELIC MUTATIONS AB We studied a consanguineous family ( Family A) from the island of Newfoundland with an autosomal recessive form of prelingual, profound, nonsyndromic sensorineural hearing loss. A genome-wide scan mapped the deafness trait to 10q21-22 (max LOD score of 4.0; D10S196) and fine mapping revealed a 16 Mb ancestral haplotype in deaf relatives. The PCDH15 gene was mapped within the critical region and was an interesting candidate because truncating mutations cause Usher syndrome type IF (USH1F) and two missense mutations have been previously associated with isolated deafness (DFNB23). Sequencing of the PCDH15 gene revealed 33 sequencing variants. Three of these variants were homozygous exclusively in deaf siblings but only one of them was not seen in ethnically matched controls. This novel c. 1583 T > A transversion predicts an amino-acid substitution of a valine with an aspartic acid at codon 528 (V528D). Like the two DFNB23 mutations, the V528D mutation in Family A occurs in a highly conserved extracellular cadherin (EC) domain of PCDH15 and is predicted to be more deleterious than the previously identified DFNB23 missense mutations (R134G and G262D). Physical assessment, vestibular and visual function testing in deaf adults ruled out syndromic deafness because of Usher syndrome. This study validates the DFNB23 designation and supports the hypothesis that missense mutations in conserved motifs of PCDH15 cause nonsyndromic hearing loss. This emerging genotype-phenotype correlation in USH1F is similar to that in several other USH1 genes and cautions against a prognosis of a dual sensory loss in deaf children found to be homozygous for hypomorphic mutations at the USH1F locus. C1 [Doucette, Lance; Merner, Nancy D.; Cooke, Sandra; Ives, Elizabeth; Galutira, Dante; Fernandez, Bridget; Green, Jane S.; Young, Terry-Lynn] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada. [Walsh, Vanessa; Walsh, Tom; Lee, Ming; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [MacLaren, Linda] Alberta Childrens Prov Gen Hosp, Dept Med Genet, Calgary, AB T2T 5C7, Canada. [Cater, Tracey] Janeway Child Hlth Ctr, Dept Audiol, St John, NF, Canada. [Wilcox, Edward R.; Shotland, Larry; Li, X. C.] NIDCD, Mol Genet Lab, NIH, Rockville, MD USA. RP Young, TL (reprint author), Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada. EM tlyoung@mun.ca OI Walsh, Tom/0000-0002-8875-0310; Young, Terry-Lynn/0000-0003-4673-6470; Doucette, Lance/0000-0002-8495-9723 FU CFI New Investigator [9384]; Newfoundland Cancer Treatment Research Foundation, Memorial University IRIF; CIHR [MOP-66974-TLY, RSH-72586]; Janeway Children's Hospital Foundation; NIH [R01 DC01076] FX Thanks to Family A for participation in the study; Herb Martin, Wendy Martin, Andree MacMillan, and Anne Duff for clinical assistance; Dr Claire-Neville Smith for her early interest in the education of deaf children; and summer student Sonny Collis. This study was supported by CFI New Investigator Award (TLY-project 9384), the Newfoundland Cancer Treatment Research Foundation, Memorial University IRIF award, CIHR operating grant (MOP-66974-TLY), the Janeway Children's Hospital Foundation, and the NIH (R01 DC01076) (M-CK). TLY holds a CIHR/Regional Partnerships Program New Investigator Award (RSH-72586) for research into deafness. NR 49 TC 14 Z9 14 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2009 VL 17 IS 5 BP 554 EP 564 DI 10.1038/ejhg.2008.231 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 437ST UT WOS:000265507900003 PM 19107147 ER PT J AU Shatunov, A Olive, M Odgerel, Z Stadelmann-Nessler, C Irlbacher, K van Landeghem, F Bayarsaikhan, M Lee, HS Goudeau, B Chinnery, PF Straub, V Hilton-Jones, D Damian, MS Kaminska, A Vicart, P Bushby, K Dalakas, MC Sambuughin, N Ferrer, I Goebel, HH Goldfarb, LG AF Shatunov, Alexey Olive, Montse Odgerel, Zagaa Stadelmann-Nessler, Christine Irlbacher, Kerstin van Landeghem, Frank Bayarsaikhan, Munkhuu Lee, Hee-Suk Goudeau, Bertrand Chinnery, Patrick F. Straub, Volker Hilton-Jones, David Damian, Maxwell S. Kaminska, Anna Vicart, Patrick Bushby, Kate Dalakas, Marinos C. Sambuughin, Nyamkhishig Ferrer, Isidro Goebel, Hans H. Goldfarb, Lev G. TI In-frame deletion in the seventh immunoglobulin-like repeat of filamin C in a family with myofibrillar myopathy SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE myofibrillar myopathy; desmin-related myopathy; limb-girdle muscular dystrophy; filamin C; small deletion mutation; German family ID A ABP-280 MOLECULES; ELECTRON-MICROSCOPY; Z-DISC; GENE CAUSES; MUSCLE; PHENOTYPE; PROTEIN; CYTOSKELETON; DISORDER; MUTATION AB Myofibrillar myopathies (MFMs) are an expanding and increasingly recognized group of neuromuscular disorders caused by mutations in DES, CRYAB, MYOT, and ZASP. The latest gene to be associated with MFM was FLNC; a p. W2710X mutation in the 24th immunoglobulin-like repeat of filamin C was shown to be the cause of a distinct type of MFM in several German families. We studied an International cohort of 46 patients from 39 families with clinically and myopathologically confirmed MFM, in which DES, CRYAB, MYOT, and ZASP mutations have been excluded. In patients from an unrelated family a 12-nucleotide deletion (c. 2997_3008del) in FLNC resulting in a predicted in-frame four-residue deletion (p. Val930_Thr933del) in the seventh repeat of filamin C was identified. Both affected family members, mother and daughter, but not unrelated control individuals, carried the p. Val930_Thr933del mutation. The mutation is transcribed and, based on myopathological features and immunoblot analysis, it leads to an accumulation of dysfunctional filamin C in the myocytes. The study results suggest that the novel p. Val930_Thr933del mutation in filamin C is the cause of MFM but also indicate that filamin C mutations are a comparatively rare cause of MFM. C1 [Shatunov, Alexey; Odgerel, Zagaa; Lee, Hee-Suk; Goldfarb, Lev G.] NINDS, Natl Inst Hlth, Bethesda, MD 20892 USA. [Olive, Montse; Ferrer, Isidro] Ciutat Sanitaria & Univ Bellvitge, Inst Neuropatol, Hosp Llobregat, Barcelona, Spain. [Stadelmann-Nessler, Christine] Univ Gottingen, Univ Med, Gottingen, Germany. [Irlbacher, Kerstin; van Landeghem, Frank] Charite Univ Med Berlin, D-13353 Berlin, Germany. [Bayarsaikhan, Munkhuu; Sambuughin, Nyamkhishig] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Goudeau, Bertrand; Vicart, Patrick] Univ Paris, UFR Biochim, F-75252 Paris, France. [Chinnery, Patrick F.; Straub, Volker; Bushby, Kate] Inst Human Genet, Newcastle Upon Tyne, Tyne & Wear, England. [Hilton-Jones, David] John Radcliffe Hosp, Oxford OX3 9DU, England. [Damian, Maxwell S.] Univ Hosp Leicester, Leicester, Leics, England. [Kaminska, Anna] Med Univ Warsaw, Warsaw, Poland. [Dalakas, Marinos C.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Goebel, Hans H.] Johannes Gutenberg Univ Mainz, Med Ctr, Mainz, Germany. RP Goldfarb, LG (reprint author), NINDS, Natl Inst Hlth, 5625 Fishers Lane,Room 4S06, Bethesda, MD 20892 USA. EM GoldfarbL@ninds.nih.gov RI Shatunov, Aleksey/E-6946-2011; OI Olive, Montse/0000-0001-5727-0165 FU National Institute of Neurological Disorders and Stroke; National Institutes of Health; Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain; UK National Commissioning Group; TREAT-NMD EU Network of Excellence [036825]; AFM [12986]; ANR [06-MRAR-039-01]; [FIS 05-1213] FX We are grateful to the members of the affected family for participation in the study. This research was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. MO was the recipient of the FIS 05-1213 grant. Additionally, MO and IF were supported by the Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain. Diagnostic and advisory service for rare neuromuscular disorders in the Newcastle upon Tyne area was funded by the UK National Commissioning Group; Newcastle University is a partner in the TREAT-NMD EU Network of Excellence (EC, 6th FP, proposal no. 036825; www.treat-nmd.eu). BG and PV were recipients of AFM Grant no. 12986 and the ANR Grant no. 06-MRAR-039-01. HHG is a member of the German MD-NET. Filamin C antibody was kindly provided by DO Furst. NR 24 TC 32 Z9 33 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAY PY 2009 VL 17 IS 5 BP 656 EP 663 DI 10.1038/ejhg.2008.226 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 437ST UT WOS:000265507900016 PM 19050726 ER PT J AU Taylor, K Rolfe, M Reynolds, N Kilanowski, F Pathania, U Clarke, D Yang, D Oppenheim, J Samuel, K Howie, S Barran, P Macmillan, D Campopian, D Dorin, J AF Taylor, Karen Rolfe, Mark Reynolds, Natalie Kilanowski, Fiona Pathania, Uday Clarke, Dave Yang, De Oppenheim, Joost Samuel, Kay Howie, Sarah Barran, Perdita Macmillan, Derek Campopian, Dominic Dorin, Julia TI Defensin-related peptide 1 (Defr1) is allelic to Defb8 and chemoattracts immature DC and CD4(+) T cells independently of CCR6 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE beta-Defensin; Chemotaxis; DC ID HUMAN BETA-DEFENSINS; DENDRITIC CELLS; ANTIMICROBIAL ACTIVITY; HUMAN BETA-DEFENSIN-3; MAMMALIAN DEFENSINS; IMMUNITY; MOUSE; EXPRESSION; INNATE; GENE AB beta-Defensins comprise a family of cationic, antimicrobial and chemoattractant peptides. The six cysteine canonical motif is retained throughout evolution and the disulphide connectivities stabilise the conserved monomer structure. A murine beta-defensin gene (Defr1) present in the main defensin cluster of C57B1/6 mice, encodes a peptide with only five of the canonical six cysteine residues. in other inbred strains of mice, the allele encodes Defb8, which has the six cysteine motif. We show here that in common with six cysteine beta-defensins, defensin-related peptide 1 (Defr1) displays chemoattractant activity for CD4(+) T cells and immature DC (iDC), but not mature DC cells or neutrophils. Murine Defb2 replicates this pattern of attraction. Defb8 is also able to attract iDC but not mature DC. Synthetic analogues of Defr1 with the six cysteines; restored (Defr1 Y5C) or with only a single cysteine (Defr1-1c(V)) chemoattract CD4(+) T cells with reduced activity, but do not chemoattract DC. beta-Defensins have previously been shown to attract iDC through CC receptor 6 (CCR6) but neither Defr1 or its related peptides nor Defb8, chemoattract cells overexpressing CCR6. Thus, we demonstrate that the canonical six cysteines of beta-defensins are not required for the chemoattractant activity of Defr1 and that neither Defr1 nor the six cysteine polymorphic variant allele Defb8, act through CCR6. C1 [Taylor, Karen; Rolfe, Mark; Reynolds, Natalie; Kilanowski, Fiona; Pathania, Uday; Dorin, Julia] Western Gen Hosp, MRC, IGMM, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Clarke, Dave; Barran, Perdita; Campopian, Dominic] Univ Edinburgh, Sch Chem, Edinburgh, Midlothian, Scotland. [Yang, De; Oppenheim, Joost] NCI, Mol Immunoregulat Lab, Ctr Canc Res Sci Applicat & Int Cooperat Frederic, Frederick, MD 21701 USA. [Samuel, Kay] Ctr Regenerat Med, SNBTS Cell Therapy Grp, Edinburgh, Midlothian, Scotland. [Howie, Sarah] Univ Edinburgh, MRC, Ctr Inflammat Res, Queens Med Res Inst, Edinburgh, Midlothian, Scotland. [Macmillan, Derek] UCL, Dept Chem, Christopher Ingold Labs, London, England. RP Dorin, J (reprint author), Western Gen Hosp, MRC, IGMM, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. EM julia.dorin@hgu.mrc.ac.uk OI Howie, Sarah/0000-0001-7291-3499; Barran, Perdita/0000-0002-7720-586X FU EPSRC; Royal Society; Cystic Fibrosis Research Trust UK; Medical Research Council; Royal Society of Edinburgh; University of Edinburgh FX This research was supported by the EPSRC, the Royal Society, Cystic Fibrosis Research Trust UK, Medical Research Council, the Royal Society of Edinburgh and the University of Edinburgh. We thank Prof. Nick Hastie for his continued enthusiasm for this project. NR 27 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAY PY 2009 VL 39 IS 5 BP 1353 EP 1360 DI 10.1002/eji.200838566 PG 8 WC Immunology SC Immunology GA 446RB UT WOS:000266137700017 PM 19404978 ER PT J AU McCrae, RR AF McCrae, Robert R. TI Personality Profiles of Cultures: Patterns of Ethos SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article DE cross-cultural; evolution; five-factor model; ethnography ID 5-FACTOR MODEL; NATIONAL CHARACTER; TRAITS; PERSPECTIVE; PSYCHOLOGY; CHIMPANZEE; ACHIEVEMENT; SITUATIONS; EMERGENCE; LANGUAGES AB Culture and the human mind are deeply interdependent, because they co-evolved. Personality traits were a preexisting feature, of the primate mind and must have left all imprint on forms of culture. Trait taxonomies can structure ethnographies, by specifying institutions that reflect the operation of traits. Facets of ethos can be assessed by expert ratings or objective indicators. Ratings of ethos in Japan and the US were reliable and yielded plausible descriptions of culture. However, measures of ethos based on the analysis of stories were not meaningfully correlated with aggregate personality traits or national character stereotypes. Profiles of ethos may provide another axis that can be used with aggregate personality trait levels to predict behaviour and understand the operation of culture. Published in 2009 by John Wiley & Sons, Ltd. C1 NIA, Lab Personal & Cognit, NIH, Dept Hlth & Human Serv,Biomed Res Ctr, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Lab Personal & Cognit, NIH, Dept Hlth & Human Serv,Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 04B329, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov NR 91 TC 9 Z9 9 U1 1 U2 15 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAY PY 2009 VL 23 IS 3 BP 205 EP 227 DI 10.1002/per.712 PG 23 WC Psychology, Social SC Psychology GA 448OF UT WOS:000266271200004 ER PT J AU Ravizzini, G Turkbey, B Kurdziel, K Choyke, PL AF Ravizzini, Gregory Turkbey, Baris Kurdziel, Karen Choyke, Peter L. TI New horizons in prostate cancer imaging SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Article DE Prostate cancer; MR imaging; Molecular imaging; PET ID POSITRON-EMISSION-TOMOGRAPHY; IN-111 CAPROMAB PENDETIDE; PHASE-I TRIAL; ENDORECTAL MR; RADICAL PROSTATECTOMY; MONOCLONAL-ANTIBODY; INITIAL-EXPERIENCE; MEMBRANE ANTIGEN; EXTRACAPSULAR EXTENSION; SEXTANT LOCALIZATION AB Prostate cancer is the most common non-cutaneous malignancy among American men. imaging has recently become more important in detection of prostate cancer since screening techniques such as digital rectal examination (DRE), prostate specific and transrectal ultrasound guided biopsy have considerable limitations in diagnosis and localization of prostate cancer. In this manuscript, we reviewed conventional, functional and targeted imaging modalities used in diagnosis and local staging of prostate cancer with exquisite images. Published by Elsevier Ireland Ltd. C1 [Ravizzini, Gregory; Turkbey, Baris; Kurdziel, Karen; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@nih.gov FU Intramural NIH HHS [Z01 BC010655-03] NR 98 TC 36 Z9 38 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAY PY 2009 VL 70 IS 2 BP 212 EP 226 DI 10.1016/j.ejrad.2008.09.019 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 456SP UT WOS:000266868900004 PM 18993004 ER PT J AU Liu, W Frank, JA AF Liu, Wei Frank, Joseph A. TI Detection and quantification of magnetically labeled cells by cellular MRI SO EUROPEAN JOURNAL OF RADIOLOGY LA English DT Review DE MRI; Cell labeling; SPIO nanoparticles; Gadolinium; Perfluorocarbon ID IRON-OXIDE NANOPARTICLES; STATIC DEPHASING REGIME; TARGETING GENE DELIVERY; MESENCHYMAL STEM-CELLS; IN-VIVO TRACKING; CONTRAST AGENT; SUPERPARAMAGNETIC NANOPARTICLES; RESONANCE TRACKING; FIELD INHOMOGENEITIES; TRANSFECTION AGENTS AB Labeling cells with superparamagnetic iron oxide (SPIO) nanoparticles, paramagnetic contrast agent (gadolinium) or perfluorocarbons allows for the possibility of tracking single or clusters of labeled cells within target tissues following either direct implantation or intravenous injection. This review summarizes the practical issues regarding detection and quantification of magnetically labeled cells with various MRI contrast agents with a focus on SPIO nanoparticles. Published by Elsevier Ireland Ltd. C1 [Liu, Wei; Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. [Liu, Wei] Philips Res N Amer, Briarcliff Manor, NY 10510 USA. RP Frank, JA (reprint author), NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bldg 10,Room B1N256,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jafrank@helix.nih.gov FU Clinical Center at the National Institutes of Health FX The intramural research program of the Clinical Center at the National Institutes of Health supported this research. We would also like to acknowledge Philips Research North America as part of a cooperative research and development agreement for providing part of the support for this study. NR 85 TC 114 Z9 120 U1 3 U2 37 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0720-048X J9 EUR J RADIOL JI Eur. J. Radiol. PD MAY PY 2009 VL 70 IS 2 BP 258 EP 264 DI 10.1016/j.ejrad.2008.09.021 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 456SP UT WOS:000266868900009 PM 18995978 ER PT J AU Klein, MK Haberberger, RV Hartmann, P Faulhammer, P Lips, KS Krain, B Wess, J Kummer, W Konig, P AF Klein, M. K. Haberberger, R. V. Hartmann, P. Faulhammer, P. Lips, K. S. Krain, B. Wess, J. Kummer, W. Koenig, P. TI Muscarinic receptor subtypes in cilia-driven transport and airway epithelial development SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE Cholinergic signal transduction; epithelial development; knockout mice; mucociliary clearance ID ACETYLCHOLINE-RECEPTOR; KNOCKOUT MICE; DEFICIENT MICE; HUMAN LUNG; STIMULATION; CELLS; RAT; PROLIFERATION; FIXATION; RELEASE AB Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1-M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect, most likely through the M1 receptor, and normalised the ATP response. M1, M4 and M5 receptor-deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development. C1 [Koenig, P.] Med Univ Lubeck, Zentrum Med Struktur & Zellbiol, Inst Anat, D-23538 Lubeck, Germany. [Klein, M. K.; Haberberger, R. V.; Hartmann, P.; Faulhammer, P.; Lips, K. S.; Krain, B.; Kummer, W.; Koenig, P.] Univ Giessen, Inst Anat & Zellbiol, Giessen, Germany. [Klein, M. K.; Haberberger, R. V.; Hartmann, P.; Faulhammer, P.; Lips, K. S.; Krain, B.; Kummer, W.; Koenig, P.] Univ Giessen, Lung Ctr, Giessen, Germany. [Haberberger, R. V.] Flinders Univ S Australia, Adelaide, SA, Australia. [Krain, B.] Univ Giessen, Abt Anaesthesie, Giessen, Germany. [Wess, J.] NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Konig, P (reprint author), Med Univ Lubeck, Zentrum Med Struktur & Zellbiol, Inst Anat, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM koenig@anat.uni-luebeck.de OI Haberberger, Rainer Viktor/0000-0001-8043-3786 FU Intramural NIH HHS [ZIA DK075020-02] NR 28 TC 25 Z9 25 U1 0 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2009 VL 33 IS 5 BP 1113 EP 1121 DI 10.1183/09031936.00015108 PG 9 WC Respiratory System SC Respiratory System GA 444RY UT WOS:000265999300022 PM 19213795 ER PT J AU Doyon, J Korman, M Morin, A Dostie, V Tahar, AH Benali, H Karni, A Ungerleider, LG Carrier, J AF Doyon, Julien Korman, Maria Morin, Amelie Dostie, Valerie Tahar, Abdallah Hadj Benali, Habib Karni, Avi Ungerleider, Leslie G. Carrier, Julie TI Contribution of night and day sleep vs. simple passage of time to the consolidation of motor sequence and visuomotor adaptation learning SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Memory consolidation; Motor learning; Sleep; Passage of daytime; Visuomotor adaptation; Motor sequence ID MEMORY CONSOLIDATION; SKILL; ACQUISITION; PERFORMANCE; MOVEMENT; INTERFERENCE; IMPROVEMENT; MECHANISMS; EXPERIENCE; DEPENDENCE AB There is increasing evidence supporting the notion that the contribution of sleep to consolidation of motor skills depends on the nature of the task used in practice. We compared the role of three post-training conditions in the expression of delayed gains on two different motor skill learning tasks: finger tapping sequence learning (FTSL) and visuomotor adaptation (VMA). Subjects in the DaySleep and ImmDaySleep conditions were trained in the morning and at noon, respectively, afforded a 90-min nap early in the afternoon and were re-tested 12 h post-training. In the NightSleep condition, subjects were trained in the evening on either of the two learning paradigms and re-tested 12 h later following sleep, while subjects in the NoSleep condition underwent their training session in the morning and were re-tested 12 h later without any intervening sleep. The results of the FTSL task revealed that post-training sleep (day-time nap or night-time sleep) significantly promoted the expression of delayed gains at 12 h post-training, especially if sleep was afforded immediately after training. In the VMA task, however, there were no significant differences in the gains expressed at 12 h post-training in the three conditions. These findings suggest that "off-line" performance gains reflecting consolidation processes in the FTSL task benefit from sleep, even a short nap, while the simple passage of time is as effective as time in sleep for consolidation of VMA to occur. They also imply that procedural memory consolidation processes differ depending on the nature of task demands. C1 [Doyon, Julien; Morin, Amelie; Tahar, Abdallah Hadj; Benali, Habib; Carrier, Julie] Univ Montreal, Funct Neuroimaging Unit, Geriatr Inst, Montreal, PQ H3W 1W5, Canada. [Doyon, Julien; Morin, Amelie; Dostie, Valerie; Tahar, Abdallah Hadj; Carrier, Julie] Univ Montreal, Ctr Rech Neuropsychol & Cognit, Dept Psychol, Montreal, PQ H2V 2S9, Canada. [Doyon, Julien; Benali, Habib] Univ Paris 06, UMR S 678, INSERM, CHU Pitie Salpetriere, F-75013 Paris, France. [Korman, Maria; Karni, Avi] Univ Haifa, Lab Funct Brain Imaging & Learning Res, Brain Behav Ctr, IL-31905 Har Hakarmel, Israel. [Morin, Amelie; Dostie, Valerie; Carrier, Julie] Hop Sacre Coeur, Ctr Etud Sommeil & Rythmes Biol, Montreal, PQ H4J 1C5, Canada. [Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Doyon, J (reprint author), Univ Montreal, Funct Neuroimaging Unit, Geriatr Inst, 4565 Queen Mary, Montreal, PQ H3W 1W5, Canada. EM julien.doyon@umontreal.ca OI Korman, Maria/0000-0003-1895-0189 FU Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council of Canada (AM) FX Support for this research was provided by the Canadian Institutes of Health Research (JD, JC, AHT and AK, HB, LGU), and by a fellowship from the Natural Sciences and Engineering Research Council of Canada (AM). The authors are grateful to Sonia Frenette, the project coordinator, to Anne Bellio and Odile Jolivet for work in developing the experimental paradigm, and to our technicians and research assistants for day-to-day study management. NR 44 TC 87 Z9 87 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2009 VL 195 IS 1 BP 15 EP 26 DI 10.1007/s00221-009-1748-y PG 12 WC Neurosciences SC Neurosciences & Neurology GA 439TI UT WOS:000265649500003 PM 19277618 ER PT J AU Redmond, TM AF Redmond, T. Michael TI Focus on Molecules: RPE65, the visual cycle retinol isomerase SO EXPERIMENTAL EYE RESEARCH LA English DT Editorial Material DE RPE65; Leber congenital amaurosis; visual cycle; isomerase; retinal pigment epithelium C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Redmond, TM (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 7,Room 303, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 FU Intramural NIH HHS [Z01 EY000260-18] NR 4 TC 11 Z9 13 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 2009 VL 88 IS 5 BP 846 EP 847 DI 10.1016/j.exer.2008.07.015 PG 2 WC Ophthalmology SC Ophthalmology GA 443GO UT WOS:000265898400001 PM 18762184 ER PT J AU Rothman, RB Baumann, MH AF Rothman, Richard B. Baumann, Michael H. TI Serotonergic drugs and valvular heart disease SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE 5-HT transporter; 5-HT2B receptor; blood 5-HT; fenfluramine; norfenfluramine; plasma 5-HT ID BIOGENIC-AMINE TRANSPORTERS; INCREASE PLASMA SEROTONIN; D-FENFLURAMINE; PLATELET SEROTONIN; M-CHLOROPHENYLPIPERAZINE; APPETITE-SUPPRESSANTS; CARCINOID-TUMORS; PULMONARY-HYPERTENSION; VALVE REGURGITATION; INTERSTITIAL-CELLS AB Background: The serotonin (5-HT) releasers (+/-)-fenfluramine and (+)-fenfluramine were withdrawn from clinical use owing to increased risk of valvular heart disease. One prevailing hypothesis (i.e., the '5-HT hypothesis') suggests that fenfluramine-induced increases in plasma 5-HT underlie the disease. Objective: Here, we critically evaluate the possible mechanisms responsible for fenfluramine-associated valve disease. Methods: Findings from in vitro and in vivo experiments performed in our laboratory are reviewed. The data are integrated with existing literature to address the validity of the 5-HT hypothesis and suggest alternative explanations. Conclusions: The overwhelming majority of evidence refutes the 5-HT hypothesis. A more likely cause of fenfluramine-induced valvulopathy is activation of 5-HT(2B) receptors on heart valves by the metabolite norfenfluramine. Future serotonergic medications should be designed to lack 5-HT(2B) agonist activity. C1 [Rothman, Richard B.; Baumann, Michael H.] NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU National Institutes of Health FX This work was supported by the Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Department of Health and Human Services. NR 84 TC 53 Z9 54 U1 1 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD MAY PY 2009 VL 8 IS 3 BP 317 EP 329 DI 10.1517/14740330902931524 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 455NV UT WOS:000266768700008 PM 19505264 ER PT J AU Waybright, TJ Veenstra, TD AF Waybright, Timothy J. Veenstra, Timothy D. TI Bringing protein biomarker discovery to the clinic SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID PROTEOMICS C1 [Waybright, Timothy J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM dprieto@ncifcrf.gov; veenstra@ncicrf.gov FU NCI NIH HHS [N01-CO-12400] NR 6 TC 0 Z9 0 U1 0 U2 1 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2009 VL 9 IS 4 BP 305 EP 307 DI 10.1586/ERM.09.22 PG 3 WC Pathology SC Pathology GA 446SC UT WOS:000266140400002 PM 19435451 ER PT J AU Nader, N Chrousos, GP Kino, T AF Nader, Nancy Chrousos, George P. Kino, Tomoshige TI Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications SO FASEB JOURNAL LA English DT Article DE brain-muscle-arnt-like protein 1; hypothalamic-pituitary-adrenal axis; GREs; GILZ; G6Pase; histone acetyltransferase ID PITUITARY-ADRENAL AXIS; CLINICAL-IMPLICATIONS; NERVOUS-SYSTEM; GENE-EXPRESSION; DNA-BINDING; KAPPA-B; STRESS; INTERACTS; PROMOTER; DISEASES AB Glucocorticoids, end products of the hypothalamic-pituitary-adrenal axis, influence functions of virtually all organs and tissues through the glucocorticoid receptor (GR). Circulating levels of glucocorticoids fluctuate naturally in a circadian fashion and regulate the transcriptional activity of GR in target tissues. The basic helix-loop-helix protein CLOCK, a histone acetyltransferase (HAT), and its heterodimer partner BMAL1 are self-oscillating transcription factors that generate circadian rhythms in both the central nervous system and periphery. We found that CLOCK/BMAL1 repressed GR-induced transcriptional activity in a HAT-activity-dependent fashion. In serum-shock-synchronized cells, transactivational activity of GR, accessed by mRNA expression of an endogenous-responsive gene, fluctuated spontaneously in a circadian fashion in reverse phase with CLOCK/BMAL1 mRNA expression. CLOCK and GR interacted with each other physically, and CLOCK suppressed binding of GR to its DNA recognition sequences by acetylating multiple lysine residues located in its hinge region. These findings indicate that CLOCK/BMAL1 functions as a reverse-phase negative regulator of glucocorticoid action in target tissues, possibly by antagonizing biological actions of diurnally fluctuating circulating glucocorticoids. Further, these results suggest that a peripheral target tissue circadian rhythm indirectly influences the functions of every organ and tissue inside the body through modulation of the ubiquitous and diverse actions of glucocorticoids.-Nader, N., Chrousos, G. P., Kino, T. Circadian rhythm transcription factor CLOCK regulates the transcriptional activity of the glucocorticoid receptor by acetylating its hinge region lysine cluster: potential physiological implications. FASEB J. 23, 1572-1583 (2009) C1 [Nader, Nancy; Chrousos, George P.; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. [Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Pediat Endocrinol, Program Reprod & Adult Endocrinol, NIH,Clin Res Ctr, Bldg 10,Rm 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX This study was funded by the Intramural Research Program of Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. We thank Drs. R. M. Evans (Salk Institute, La Jolla, CA, USA), G. L. Hager (National Cancer Institute, Bethesda, MD, USA), G. A. FitzGerald (University of Pennsylvania, Philadelphia, PA, USA), P. Sassone-Corsi (University of California, Irvine, CA, USA), and J. H. Segars (NIH, Bethesda, MD, USA) for providing plasmids and K. Zachman and Dr. T. Shibata for superb technical assistance. NR 56 TC 129 Z9 132 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 2009 VL 23 IS 5 BP 1572 EP 1583 DI 10.1096/fj.08-117697 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 453ZP UT WOS:000266651700032 PM 19141540 ER PT J AU Zheng, B Han, M Bernier, M Wen, JK AF Zheng, Bin Han, Mei Bernier, Michel Wen, Jin-Kun TI Nuclear actin and actin-binding proteins in the regulation of transcription and gene expression SO FEBS JOURNAL LA English DT Review DE actin dynamics; actin-binding protein; chromatin remodeling; gene regulation; muscle-specific gene; nuclear actin; nuclear receptor; ribonucleoprotein; RNA polymerases; transcription complex ID SERUM RESPONSE FACTOR; RNA-POLYMERASE-II; PROSTATE-CANCER CELLS; MUSCLE LIM PROTEIN; ANDROGEN RECEPTOR TRANSACTIVATION; CHROMATIN REMODELING COMPLEX; A-BOUND PEBP2-BETA/CBF-BETA; FILAMIN-A; F-ACTIN; LIGAND-BINDING AB Nuclear actin is involoved in the transcription of all three RNA polymerases, in chromatin remodeling and in the formation of heterogeneous nuclear ribonucleoprotein complexes, as well as in recruitment of the histone modifier to the active gene. In addition, actin-binding proteins (ABPs) control actin nucleation, bundling, filament capping, fragmentation and monomer availability in the cytoplasm. In recent years, more and more attention has focused on the role of actin and ABPs in the modulation of the subcellular localization of transcriptional regulators. This review focuses on recent developments in the study of transcription and transcriptional regulation by nuclear actin, and the regulation of muscle-specific gene expression, nuclear receptor and transcription complexes by ABPs. Among the ABPs, striated muscle activator of Rho signaling and actin-binding LIM protein regulate actin dynamics and serum response factor-dependent muscle-specific gene expression. Functionally and structurally unrelated cytoplasmic ABPs interact cooperatively with nuclear receptor and regulate its transactivation. Furthermore, ABPs also participate in the formation of transcription complexes. C1 [Zheng, Bin; Han, Mei; Wen, Jin-Kun] Hebei Med Univ, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China. [Bernier, Michel] NIA, NIH, Clin Invest Lab, Baltimore, MD 21224 USA. RP Wen, JK (reprint author), Hebei Med Univ, Dept Biochem & Mol Biol, 361 Zhongshan E Rd, Shijiazhuang 050017, Peoples R China. EM wjk@hebmu.edu.cn RI Cheng, Yunhui/A-5668-2010; OI Bernier, Michel/0000-0002-5948-368X FU Program for Major State Basic Research Development Program of China [2008CB517402]; National Natural Science Foundation of the People's Republic of China [30770787, 30670845, 30871272]; New Century Excellent Talents in University [NCET-05-0261]; Key Project of Chinese Ministry of Education [206016]; Hebei Natural Science Foundation of the People's Republic of China [C2008001049]; NIH, National Institute on Aging FX This work was supported by the Program for Major State Basic Research Development Program of China (No. 2008CB517402), the National Natural Science Foundation of the People's Republic of China (No. 30770787, 30670845, 30871272), the New Century Excellent Talents in University (No. NCET-05-0261), the Key Project of Chinese Ministry of Education (No. 206016), and the Hebei Natural Science Foundation of the People's Republic of China (No. C2008001049). This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 124 TC 78 Z9 81 U1 0 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD MAY PY 2009 VL 276 IS 10 BP 2669 EP 2685 DI 10.1111/j.1742-4658.2009.06986.x PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 438IQ UT WOS:000265549500002 PM 19459931 ER PT J AU Wei, QX Clair, JBS Fu, T Stratton, P Nieman, LK AF Wei, Qingxiang Clair, J. Benjamin St Fu, Teresa Stratton, Pamela Nieman, Lynnette K. TI Reduced expression of biomarkers associated with the implantation window in women with endometriosis SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the Endocrine-Society CY JUN 24-27, 2006 CL Boston, MA SP Endocrine Soc DE GdA; OPN; LPA3; HOXA10; endometrium; endometriosis; menstrual cycle; immunohistochemistry ID MENSTRUAL-CYCLE; HOXA10 EXPRESSION; GENE-EXPRESSION; GLYCODELIN-A; OSTEOPONTIN; INTEGRINS; FAILURE; PROTEIN; TISSUE; ROLES AB Objective: To evaluate the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis. Design: Prospective observational study. Setting: Clinical research center. Patient(s): Twenty-four women with endometriosis and 23 healthy volunteers of similar age. Intervention(s): Secretory phase endometrial biopsy. Main Outcome Measure(s): Expression of immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 in eutopic endometrium. Result(s): Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. Conclusion(s): The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are P dependent, these findings suggest the possibility of reduced endometrial P action in this population. (Fertil Steril (R) 2009;91:1686-91. (C)2009 by American Society for Reproductive Medicine.) C1 [Nieman, Lynnette K.] NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bldg 10,Room E1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov FU Intramural NIH HHS [Z01 HD000637-14] NR 35 TC 54 Z9 65 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP 1686 EP 1691 DI 10.1016/j.fertnstert.2008.02.121 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444GR UT WOS:000265969200012 PM 18672236 ER PT J AU Lash, MM Armstrong, A AF Lash, Marcy Maguire Armstrong, Alicia TI Impact of obesity on women's health SO FERTILITY AND STERILITY LA English DT Article DE Obesity; puberty; dysfunctional uterine bleeding; contraception; anovulation; infertility; miscarriage; ART ID POLYCYSTIC-OVARY-SYNDROME; RECURRENT MISCARRIAGE; DOUBLE-BLIND; FEMALE MICE; LEPTIN; WEIGHT; OVERWEIGHT; METFORMIN; SAFETY; RISK AB Objective: To review the impacts of obesity on women's reproductive health and fertility. Design: Literature review. Setting: Academic medical center. Patient(s): Forty articles are referenced. The number of patients evaluated in each of the studies varies from 33 to 213,208. Intervention(s): Articles were identified from an Ovid/Medline search using the search terms obesity, dysfunctional uterine bleeding, contraception, miscarriage, infertility. and weight loss. Main Outcome Measure(s): The impacts of obesity on reproductive health and fertility. Result(s): Obesity is associated with early puberty, aberrant menstrual patterns, decreased contraceptive efficacy, ovulatory disorders, an increased miscarriage rate, and worse assisted reproductive technology outcomes. Losing weight can ameliorate many of these problems. Conclusion(s): Obesity is one of the most significant causes of morbidity and mortality in the U.S. Providers must educate patients about the impacts of obesity on reproductive health and fertility. (Fertil Steril (R) 2009;91:1712-6. (C)2009 by American Society for Reproductive Medicine.) C1 [Lash, Marcy Maguire] Tufts Univ New England Med Ctr, Boston, MA USA. [Armstrong, Alicia] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Armstrong, A (reprint author), Bldg 10 CRC,1-E-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM armstroa@mail.nih.gov FU Intramural NIH HHS NR 38 TC 28 Z9 30 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP 1712 EP 1716 DI 10.1016/j.fertnstert.2008.02.141 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444GR UT WOS:000265969200016 PM 18410940 ER PT J AU Malik, M Mendoza, M Payson, M Catherino, WH AF Malik, Minnie Mendoza, Mirian Payson, Mark Catherino, William H. TI Curcumin, a nutritional supplement with antineoplastic activity, enhances leiomyoma cell apoptosis and decreases fibronectin expression SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 13-17, 2007 CL Washington, DC SP Amer Soc Reprod Med DE Leiomyoma; myometrium; curcumin; apoptosis; MAP kinase; NF-kappa B; fibronectin ID NF-KAPPA-B; LEUKEMIA HL-60 CELLS; BCL-X-L; UTERINE LEIOMYOMAS; IN-VITRO; DOWN-REGULATION; TRANSCRIPTION FACTORS; PROTEIN EXPRESSION; GENE-EXPRESSION; MELANOMA-CELLS AB Objective: To determine if curcumin has an antiproliferative effect on leiomyoma cells via apoptosis induction and whether curcumin impacts extracellular matrix (ECM) production by assessing the fibronectin expression in leiomyoma cells treated with curcumin. Design: Tissue culture study of immortalized human leiomyoma and patient-matched myometrial cells treated with curcumin. Setting: University hospital. Patient(s): Immortalized leiomyoma and myometrial cells from patients with symptomatic leiomyomata. Intervention(S): Tissue culture, followed by proliferation studies, RNA, and protein analysis. Main Outcome Measure(s): Cell proliferation, alteration in apoptotic signaling pathways. Result(s): Curcumin demonstrated an antiproliferative effect on leiomyoma cell tines (IC50 = 20 mu M). Importantly, no statistically significant inhibition of growth was observed when patient-matched myometrial cells were exposed to equivalent concentrations of curcumin. Curcumin stimulated caspase-3 and caspase-9 expression while inhibiting extracellular signal-regulated kinase I (ERK 1), ERK 2, and nuclear factor kappa B (NF-kappa B), suggesting regulation of leiomyocyte apoptosis. Finally, curcumin inhibited expression of fibronectin in leiomyoma cells. Conclusion(s): Our findings demonstrate that curcumin inhibited uterine leiomyoma cell proliferation via regulation of the apoptotic pathway, and inhibited production of the ECM component fibronectin. Curcumin provides a novel direction for leiomyoma. therapies. (Fertil Steril (R) 2009;91:2177-84. (C) 2009 by American Society for Reproductive Medicine.) C1 [Malik, Minnie; Mendoza, Mirian; Payson, Mark; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. [Payson, Mark; Catherino, William H.] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM wcatherino@usuhs.mil OI Malik, Minnie/0000-0003-1129-6575 FU Intramural NIH HHS NR 74 TC 22 Z9 24 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP 2177 EP 2184 DI 10.1016/j.fertnstert.2008.03.045 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 444GS UT WOS:000265969300029 PM 18555241 ER PT J AU Bondy, C Rosing, D Reindollar, R AF Bondy, Carolyn Rosing, Douglas Reindollar, Richard TI Cardiovascular risks of pregnancy in women with Turner syndrome SO FERTILITY AND STERILITY LA English DT Letter C1 [Bondy, Carolyn] NICHHD, NIH, Turner Syndrome Soc Med Advisory Board, Bethesda, MD 20892 USA. [Rosing, Douglas] NHLBI, NIH, Bethesda, MD 20892 USA. [Reindollar, Richard] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Bondy, C (reprint author), NICHHD, NIH, Turner Syndrome Soc Med Advisory Board, Bethesda, MD 20892 USA. NR 8 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP E31 EP E32 DI 10.1016/j.fertnstert.2009.01.061 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 668OV UT WOS:000283280200040 PM 19342026 ER PT J AU Schisterman, EF Whitcomb, BW Ruopp, M AF Schisterman, Enrique F. Whitcomb, Brian W. Ruopp, Marcus TI Evidence of absence or absence of evidence? A reanalysis of the effects of low-dose aspirin in in vitro fertilization Reply SO FERTILITY AND STERILITY LA English DT Letter ID METAANALYSIS C1 [Schisterman, Enrique F.; Whitcomb, Brian W.; Ruopp, Marcus] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. OI Schisterman, Enrique/0000-0003-3757-641X NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2009 VL 91 IS 5 BP E22 EP E22 DI 10.1016/j.fertnstert.2008.12.070 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 668OV UT WOS:000283280200031 ER PT J AU Ehrenshaft, M Silva, SO Perdivara, I Bilski, P Sik, RH Chignell, CF Torner, KB Mason, RP AF Ehrenshaft, Marilyn Silva, Sueli de Oliveira Perdivara, Irina Bilski, Piotr Sik, Robert H. Chignell, Colin F. Torner, Kenneth B. Mason, Ronald P. TI Immunological detection of N-formylkynurenine in oxidized proteins SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE N-formylkynurenine; Oxidized proteins; Tryptophan; Immunological detection; Antibodies; Superoxide dismutase; Myoglobin; Mass spectrometry; Free radicals ID AMYOTROPHIC-LATERAL-SCLEROSIS; ZN-SUPEROXIDE-DISMUTASE; TRYPTOPHAN RESIDUES; POSTTRANSLATIONAL MODIFICATION; HYDROGEN-PEROXIDE; AMINO-ACIDS; HUMAN CU; AGGREGATION; IDENTIFICATION; OXIDATION AB Reactions of tryptophan residues in proteins with radical and other oxidative species frequently lead to cleavage of the indole ring, modifying tryptophan residues into N-formylkynurenine (NFK) and kynurenine. Tryptophan modification has been detected in physiologically important proteins and has been associated with a number of human disease conditions. Modified residues have been identified through various combinations of proteomic analyses, tryptic digestion, HPLC, and mass spectrometry. Here we present a novel, immunological approach using polyclonal antiserum for detection of NFK. The specificity of our antiserum is confirmed using photooxidation and radical-mediated oxidation of proteins with and without tryptophan residues. The sensitivity of our antiserum is validated through detection of NFK in photooxidized myoglobin (two tryptophan residues) and in carbonate radical-oxidized human SOD1, which contains a single tryptophan residue. Analysis of photooxidized milk also shows that our antiserum can detect NFK residues in a mixture of proteins. Results from mass spectrometric analysis of photooxidized myoglobin samples corroborate the immunological data, detecting an increase in NFK content as the extent of photooxidation increases. Published by Elsevier Inc. C1 [Ehrenshaft, Marilyn; Silva, Sueli de Oliveira; Sik, Robert H.; Chignell, Colin F.; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Perdivara, Irina; Torner, Kenneth B.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Ehrenshaft, M (reprint author), NIEHS, Pharmacol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM ehrensh1@niehs.nih.gov FU NIH; NIEHS FX We thank B. Jean Corbett and Mary J. Mason for valuable help in the preparation of the manuscript. This work was supported by the Intramural Research Program of the NIH, NIEHS. We dedicate this paper to the memory of Colin F. Chignell. NR 31 TC 36 Z9 36 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2009 VL 46 IS 9 BP 1260 EP 1266 DI 10.1016/j.freeradbiomed.2009.01.020 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 434OX UT WOS:000265285100003 PM 19353782 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, Chung-Jyi Leitzmann, Michael F. Willett, Walter C. Giovannucci, Edward L. TI Statin Use and the Risk of Cholecystectomy in Women SO GASTROENTEROLOGY LA English DT Article ID HMG-COA REDUCTASE; CHOLESTEROL GALLSTONE DISEASE; DEPENDENT DIABETIC-PATIENTS; BILE LIPID-COMPOSITION; COENZYME-A REDUCTASE; INHIBITOR PRAVASTATIN; COMPETITIVE INHIBITOR; INSULIN SENSITIVITY; SATURATION INDEX; PRAIRIE DOGS AB Background & Aims: Statins can reduce biliary cholesterol secretion independently of their ability to inhibit cholesterol synthesis. Statins also prevent the formation of gallstones in animal studies, although the effect of statins on human gallstone disease has been controversial. Methods: We examined the relationship between the use of statins and the risk of cholecystectomy in a cohort of US women. As part of the prospective Nurses' Health Study, participants biennially reported their history of gallstone disease and whether they had undergone cholecystectomy. Women also reported lifetime use of statins retrospectively in 2000. We conducted a retrospective analysis of statin using data collected in 2000, to define use from 1994 forward, and a prospective analysis for general lipid-lowering drugs from 1994 to 2004. Results: In the statin analysis we ascertained 2479 cases of cholecystectomy during 305,197 person-years of follow-up evaluation. The multivariate relative risk for current statin users, compared with nonusers, was 0.82 (95% confidence interval, 0.70-0.96). In the analysis of general cholesterol-lowering drugs, we ascertained 3420 cases of cholecystectomy during 511,411 person-years of follow-up evaluation. Compared with nonusers, the multivariate relative risk for current users of general cholesterol-lowering drugs, mostly statins in this cohort, was 0.88 (95% confidence interval, 0.79-0.98). Conclusions: Statin use appears to reduce the risk of cholecystectomy in women. C1 [Tsai, Chung-Jyi] Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. [Tsai, Chung-Jyi; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. [Tsai, Chung-Jyi; Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Leitzmann, Michael F.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075, P01 CA055075]; NIDDK NIH HHS [P30 DK046200, DK46200] NR 55 TC 37 Z9 39 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2009 VL 136 IS 5 BP 1593 EP 1600 DI 10.1053/j.gastro.2009.01.042 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 440WQ UT WOS:000265730800022 PM 19208351 ER PT J AU Huda, A Marino-Ramirez, L Landsman, D Jordan, IK AF Huda, Ahsan Marino-Ramirez, Leonardo Landsman, David Jordan, I. King TI Repetitive DNA elements, nucleosome binding and human gene expression SO GENE LA English DT Article DE Transposable elements; Nucleosome binding; Epigenetics; Simple sequence repeats; Gene regulation; Promoter architecture; Human genome ID TRANSPOSON-FREE REGIONS; GENOME EVOLUTION; HUMAN MICRORNAS; SELFISH DNA; SEQUENCE; DATABASE; HETEROCHROMATIN; DIVERGENCE; SIMILARITY; RETROPOSON AB We evaluated the epigenetic contributions of repetitive DNA elements to human gene regulation. Human proximal promoter sequences show distinct distributions of transposable elements (TEs) and simple sequence repeats (SSRs). TEs are enriched distal from transcriptional start sites (TSSs) and their frequency decreases closer to TSSs, being largely absent from the core promoter region. SSRs, on the other hand, are found at low frequency distal to the TSS and then increase in frequency starting similar to 150 bp upstream of the TSS. The peak of SSR density is centered around the -35 bp position where the basal transcriptional machinery assembles. These trends in repetitive sequence distribution are strongly correlated, positively for TFs and negatively for SSRs, with relative nucleosome binding affinities along the promoters. Nucleosomes bind with highest probability distal from the TSS and the nucleosome binding affinity steadily decreases reaching its nadir just upstream of the TSS at the same point where SSR frequency is at its highest. Promoters that are enriched for TEs are more highly and broadly expressed, on average, than promoters that are devoid of TEs. In addition, promoters that have similar repetitive DNA profiles regulate genes that have more similar expression patterns and encode proteins with more similar functions than promoters that differ with respect to their repetitive DNA. Furthermore, distinct repetitive DNA promoter profiles are correlated with tissue-specific patterns of expression. These observations indicate that repetitive DNA elements mediate chromatin accessibility in proximal promoter regions and the repeat content of promoters is relevant to both gene expression and function. (C) 2009 Elsevier B.V. All rights reserved. C1 [Huda, Ahsan; Jordan, I. King] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Marino-Ramirez, Leonardo; Landsman, David] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Marino-Ramirez, Leonardo] CORPOICA, Corp Colombiana Invest Agr, Biotechnol & Bioind Ctr, Computat Biol & Bioinformat Unit, Bogota, Colombia. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, 310 Ferst Dr, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU NIH; NLM; NCBI; Corporacion Colombiana de Investigacion Agropecuaria - CORPOICA; Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology [BR-4839] FX This research was supported in part by the Intramural Research Program of the NIH, NLM, NCBI. LMR is supported by Corporacion Colombiana de Investigacion Agropecuaria - CORPOICA. IKJ was supported by an Alfred P. Sloan Research Fellowship in Computational and Evolutionary Molecular Biology (BR-4839). The authors would like to thank Lee S. Katz andjittima Piriyapongsa for helpful discussions and technical advice. NR 55 TC 16 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 1 PY 2009 VL 436 IS 1-2 BP 12 EP 22 DI 10.1016/j.gene.2009.01.013 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 435KO UT WOS:000265343000003 PM 19393174 ER PT J AU Sareen, J Pagura, J Grant, B AF Sareen, Jitender Pagura, Jina Grant, Bridget TI Is intimate partner violence associated with HIV infection among women in the United States? SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Intimate partner violence; Sexual behavior; HIV; Risk factors; Epidemiology ID GENERAL-POPULATION SAMPLE; HEALTH-CARE SETTINGS; ALCOHOL-USE-DISORDER; LOW-INCOME WOMEN; RELATIONSHIP POWER; DOMESTIC VIOLENCE; SOUTH-AFRICA; RISK; PREVALENCE; MULTICOUNTRY AB Objective: This study sought to examine the association between intimate partner violence (IPV) and human immunodeficiency virus (HIV) infection among a large representative sample of US women. Methods: Data came from the National Epidemiologic Survey on Alcohol and Related Conditions (age, 20 years and older). The present analysis utilized the subsample of women who reported being in a relationship in the last year (n=13,928). Participants were asked whether they had experienced physical or sexual violence from their partner in the last year, as well as whether they had been diagnosed with HIV by a health care professional. Results: Past year IPV and HIV prevalence estimates among women in romantic relationships in the United States were 5.5% and 0.17%, respectively. In models adjusting for sociodemographic factors and risky sexual behaviors (e,g., age of first intercourse), IPV was significantly associated with HIV infection (adjusted odds ratios=3.44, 95% confidence interval=1.28-9.22). We also found that 11.8% of the cases of HIV infection among women were attributable to past year IPV. Conclusions: The present study demonstrates a strong association between Wand HIV in a representative sample of US women. Screening and prevention programs need to be aware of this important association. (C) 2009 Published by Elsevier Inc. C1 [Sareen, Jitender; Pagura, Jina] Univ Manitoba, Dept Psychiat & Psychol, Winnipeg, MB R3E 3N4, Canada. [Grant, Bridget] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. RP Sareen, J (reprint author), Univ Manitoba, Dept Psychiat & Psychol, Winnipeg, MB R3E 3N4, Canada. EM sareen@cc.umanitoba.ca FU Canadian Institutes of Health Research New Investigator award [153248]; Social Sciences and Humanities Research Council Canada Graduate Scholarship (Pagura); National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse FX Preparation of this article was supported by a Canadian Institutes of Health Research New Investigator award to Dr. Sareen (#153248) and a Social Sciences and Humanities Research Council Canada Graduate Scholarship (Pagura). The National Epidemiologic Survey on Alcohol and Related Conditions was supported by the National Institute on Alcohol Abuse and Alcoholism and the National Institute on Drug Abuse. NR 30 TC 47 Z9 48 U1 6 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD MAY-JUN PY 2009 VL 31 IS 3 BP 274 EP 278 DI 10.1016/j.genhosppsych.2009.02.004 PG 5 WC Psychiatry SC Psychiatry GA 445DF UT WOS:000266029200010 PM 19410107 ER PT J AU Jung, J Sun, B Kwon, D Koller, DL Foroud, TM AF Jung, Jeesun Sun, Bin Kwon, Deukwoo Koller, Daniel L. Foroud, Tatiana M. TI Allelic-Based Gene-Gene Interaction Associated With Quantitative Traits SO GENETIC EPIDEMIOLOGY LA English DT Article DE quantitative trait loci; allelic test; interaction effect; blood pressure ID LINKAGE DISEQUILIBRIUM; PRESSURE; MODELS; LOCI AB Recent studies have shown that quantitative phenotypes may be influenced not only by multiple single nucleotide polymorphisms (SNPs) within a gene but also by the interaction between SNPs at unlinked genes. We propose a new statistical approach that can detect gene-gene interactions at the allelic level which contribute to the phenotypic variation in a quantitative trait. By testing for the association of allelic combinations at multiple unlinked loci with a quantitative trait, we call detect the SNP allelic interaction whether or not it call be detected as a main effect. Our proposed method assigns a score to unrelated subjects according to their allelic combination inferred from observed genotypes at two or more unlinked SNPs, and then tests for the association of the allelic score with a quantitative trait. To investigate the statistical properties of the proposed method, we performed a simulation study to estimate type I error rates and power and demonstrated that this allelic approach achieves greater power than the more commonly used genotypic approach to test for gene-gene interaction. As all example, the proposed method was applied to data obtained as part of a candidate gene study of sodium retention by the kidney. We found that this method detects an interaction between the calcium-sensing receptor gene (CaSR), the chloride channel gene (CLCNKB) and the Na, K, 2Cl cotransporter gene (CLC12A1) that contributes to variation in diastolic blood pressure. Genet. Epidemiol. 33: 332-343, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Jung, Jeesun; Sun, Bin; Koller, Daniel L.; Foroud, Tatiana M.] Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Kwon, Deukwoo] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Jung, J (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. EM jeejung@iupui.edu FU Indiana Genomics Initiative (INGENR); Lilly Endowment Inc. FX Contract grant sponsors: Indiana Genomics Initiative (INGENR), Lilly Endowment Inc. NR 12 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD MAY PY 2009 VL 33 IS 4 BP 332 EP 343 DI 10.1002/gepi.20385 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 440UJ UT WOS:000265724900007 PM 19058262 ER PT J AU Harris, JN Bowen, DJ Kuniyuki, A McIntosh, L FitzGerald, LM Ostrander, EA Stanford, JL AF Harris, Julie N. Bowen, Deborah J. Kuniyuki, Alan McIntosh, Laura FitzGerald, Liesel M. Ostrander, Elaine A. Stanford, Janet L. TI Interest in genetic testing among affected men from hereditary prostate cancer families and their unaffected male relatives SO GENETICS IN MEDICINE LA English DT Article DE prostate cancer; family; hereditary; genetic test; psychosocial ID BREAST-OVARIAN CANCER; AFRICAN-AMERICAN MEN; COLORECTAL-CANCER; COLON-CANCER; ETHNIC-DIFFERENCES; RISK PERCEPTION; ATTITUDES; SUSCEPTIBILITY; WOMEN; HISTORY AB Purpose: The objective of this study was to evaluate potential sociodemographic, medical, psychosocial, and behavioral correlates of interest in genetic testing in men from hereditary prostate cancer families. Methods: Family members affected with prostate cancer (n = 559) and their unaffected male relatives (n = 370) completed a mailed survey. Multivariable logistic regression models were used to examine the association between potential correlates and interest in genetic testing for prostate cancer. Results: Forty-five percent of affected and 56% of unaffected men reported that they definitely would take a genetic test for prostate cancer. More affected men reported high levels of familiarity with genetic testing than unaffected men (46 vs. 25%). There were several variables that were significantly correlated with interest in either affected or unaffected men, but only age and familiarity with genetics were significant in both groups. After controlling for confounding variables, only familiarity remained a significant correlate in both groups. Conclusions: The contrast between low levels of familiarity with genetics and high test interest among unaffected men highlights the need for increased educational efforts targeting hereditary prostate cancer families. Overall, results illuminated several novel characteristics of men from hereditary prostate cancer families that should be considered when developing future informed consent procedures or educational materials for prostate cancer genetic testing. Genet Med 2009:11(5):344-355. C1 [Harris, Julie N.] Univ Calif San Francisco, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, San Francisco, CA 94118 USA. [Harris, Julie N.] Univ Calif Berkeley, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, Berkeley, CA 94720 USA. [Bowen, Deborah J.] Boston Univ, Dept Social & Behav Sci, Boston, MA 02215 USA. [Kuniyuki, Alan] Fred Hutchinson Canc Res Ctr, Program Canc Prevent, Seattle, WA 98104 USA. [McIntosh, Laura; FitzGerald, Liesel M.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Stanford, Janet L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Harris, JN (reprint author), Univ Calif San Francisco, Robert Wood Johnson Fdn, Hlth & Soc Scholars Program, 3333 Calif St, San Francisco, CA 94118 USA. EM harrisjn@chc.ucsf.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU Biobehavioral Cancer Prevention and Control [R25 CA092408]; Pacific Northwest Prostate Cancer SPORE [P50 CA097186]; National Cancer Institute [RO1 CA080122]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX This work was supported by Biobehavioral Cancer Prevention and Control Training Grant R25 CA092408 (JNH), Pacific Northwest Prostate Cancer SPORE Career Development Program Fellowship P50 CA097186 (LMF), and RO1 CA080122 from the National Cancer Institute, with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute (EAO). Julie N Harris is a Robert Wood Johnson Foundation Health & Society Scholar at the University of California in San Francisco and Berkeley, CA. They also thank all of the individuals who participated in the PROGRESS study. NR 48 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY PY 2009 VL 11 IS 5 BP 344 EP 355 DI 10.1097/GIM.0b013e31819b2425 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 449HQ UT WOS:000266321800006 PM 19346959 ER PT J AU Merkens, LS Wassif, C Healy, K Pappu, AS DeBarber, AE Penfield, JA Lindsay, RA Roullet, JB Porter, FD Steiner, RD AF Merkens, Louise S. Wassif, Christopher Healy, Kristy Pappu, Anuradha S. DeBarber, Andrea E. Penfield, Jennifer A. Lindsay, Rebecca A. Roullet, Jean-Baptiste Porter, Forbes D. Steiner, Robert D. TI Smith-Lemli-Opitz syndrome and inborn errors of cholesterol synthesis: summary of the 2007 SLO/RSH Foundation scientific conference sponsored by the National Institutes of Health SO GENETICS IN MEDICINE LA English DT Article DE Smith-Lemli-Opitz syndrome; cholesterol; hedgehog proteins; neurosteroids; cholesterol transport; mevalonate kinase deficiency; Niemann-Pick type C; oxysterols; CHILD syndrome ID GOLDEN SYRIAN-HAMSTER; PRENATAL-DIAGNOSIS; FETAL CIRCULATION; MODEL; BIOSYNTHESIS; METABOLISM; DEFICIENT; TRANSPORT; STEROLS; DISEASE AB In June 2007, the Smith-Lemli-Opitz/RSH Foundation held a scientific conference hosted jointly by Dr. Robert Steiner from Oregon Health & Science University and Dr. Forbes D. Porter from The Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health. The main goal of this meeting was to promote interaction between scientists with expertise in cholesterol homeostasis, brain cholesterol metabolism, developmental biology, and oxysterol and neurosteroid biochemistry, clinicians researching and treating patients with Smith-Lemli-Opitz syndrome, the patient support organization and families. This report summarizes the presentations and discussions at the conference, represents the conference proceedings, and is intended to foster collaborative research and Ultimately improve understanding and treatment of Smith-Lemli-Opitz syndrome and other inborn errors of cholesterol synthesis. Genet Med 2009: 11(5):359-364. C1 [Merkens, Louise S.; Healy, Kristy; Penfield, Jennifer A.; Roullet, Jean-Baptiste; Steiner, Robert D.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Wassif, Christopher; Porter, Forbes D.] NICHD, Heritable Disorders Branch, NIH, DHHS, Bethesda, MD USA. [Pappu, Anuradha S.; DeBarber, Andrea E.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Child Dev & Rehabil Ctr, Dept Physiol & Pharmacol, Portland, OR 97239 USA. [Lindsay, Rebecca A.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Child Dev & Rehabil Ctr, Dept Neurosurg, Portland, OR 97239 USA. [Steiner, Robert D.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Ctr, Child Dev & Rehabil Ctr, Dept Mol & Med Genet, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Doernbecher Mem Hosp Children, Portland, OR 97239 USA. RP Merkens, LS (reprint author), Oregon Hlth & Sci Univ, Dept Pediat, Mail Code CDRC,707 SW Gaines Rd, Portland, OR 97239 USA. EM merkensl@ohsu.edu OI Steiner, Robert/0000-0003-4177-4590; Wassif, Christopher/0000-0002-2524-1420 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [R01 HL073980 03S1]; National Institutes of Health Office of Rare Diseases FX This work was supported by the Grant awards: R01 HL073980 03S1 (R01 supplement) (to R.S.); from the intramural research programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Rare Diseases (to R. S. F. P.). NR 34 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY PY 2009 VL 11 IS 5 BP 359 EP 364 DI 10.1097/GIM.0b013e31819b246e PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 449HQ UT WOS:000266321800008 PM 19452638 ER PT J AU Nielsen, R Hubisz, MJ Hellmann, I Torgerson, D Andres, AM Albrechtsen, A Gutenkunst, R Adams, MD Cargill, M Boyko, A Indap, A Bustamante, CD Clark, AG AF Nielsen, Rasmus Hubisz, Melissa J. Hellmann, Ines Torgerson, Dara Andres, Aida M. Albrechtsen, Anders Gutenkunst, Ryan Adams, Mark D. Cargill, Michele Boyko, Adam Indap, Amit Bustamante, Carlos D. Clark, Andrew G. TI Darwinian and demographic forces affecting human protein coding genes SO GENOME RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; NATURAL-SELECTION; HUMAN GENOME; FREQUENCY-SPECTRUM; POSITIVE SELECTION; SNP DATA; SUBDIVIDED POPULATION; ADAPTIVE EVOLUTION; STATISTICAL TESTS; DNA POLYMORPHISM AB Past demographic changes can produce distortions in patterns of genetic variation that can mimic the appearance of natural selection unless the demographic effects are explicitly removed. Here we fit a detailed model of human demography that incorporates divergence, migration, admixture, and changes in population size to directly sequenced data from 13,400 protein coding genes from 20 European-American and 19 African-American individuals. Based on this demographic model, we use several new and established statistical methods for identifying genes with extreme patterns of polymorphism likely to be caused by Darwinian selection, providing the first genome-wide analysis of allele frequency distributions in humans based on directly sequenced data. The tests are based on observations of excesses of high frequency-derived alleles, excesses of low frequency-derived alleles, and excesses of differences in allele frequencies between populations. We detect numerous new genes with strong evidence of selection, including a number of genes related to psychiatric and other diseases. We also show that microRNA controlled genes evolve under extremely high constraints and are more likely to undergo negative selection than other genes. Furthermore, we show that genes involved in muscle development have been subject to positive selection during recent human history. In accordance with previous studies, we find evidence for negative selection against mutations in genes associated with Mendelian disease and positive selection acting on genes associated with several complex diseases. C1 [Nielsen, Rasmus; Hellmann, Ines; Albrechtsen, Anders] Univ Copenhagen, Dept Biol, DK-2100 Kbh O, Denmark. [Nielsen, Rasmus; Hellmann, Ines; Albrechtsen, Anders] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Nielsen, Rasmus; Hellmann, Ines; Albrechtsen, Anders] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. [Hubisz, Melissa J.; Torgerson, Dara] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Hubisz, Melissa J.; Gutenkunst, Ryan; Boyko, Adam; Indap, Amit; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Andres, Aida M.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Adams, Mark D.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Cargill, Michele] Navigenics, Redwood Shores, CA 94065 USA. [Clark, Andrew G.] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Nielsen, R (reprint author), Univ Copenhagen, Dept Biol, DK-2100 Kbh O, Denmark. EM Rasmus@binf.ku.dk RI Nielsen, Rasmus/D-4405-2009; Albrechtsen, Anders/K-4281-2013; Andres, Aida/B-4088-2014 OI Nielsen, Rasmus/0000-0003-0513-6591; Albrechtsen, Anders/0000-0001-7306-031X; Andres, Aida/0000-0002-8590-9672 FU NIH [HG003229]; National Danish Science Foundation FX This research was supported by NIH grant HG003229 to A. G. C., R. N., and C. D. B., and a grant to R. N. from the National Danish Science Foundation. The data from this study were obtained from more than 18 million sequencing reads obtained from the Celera Genomics sequencing center in Rockville, MD. We thank J. Duff, C. Evans, S. Ferriera, C. Forbes, C. Gire, B. Murphy, M. A. Rydland, B. Small, and G. Wang for technical contributions. NR 75 TC 87 Z9 89 U1 2 U2 42 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAY PY 2009 VL 19 IS 5 BP 838 EP 849 DI 10.1101/gr.088336.108 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 440AA UT WOS:000265668800017 PM 19279335 ER PT J AU Moquin, B Blackman, MR Mitty, E Flores, S AF Moquin, Barbara Blackman, Marc R. Mitty, Ethel Flores, Sandi TI Complementary and Alternative Medicine (CAM) SO GERIATRIC NURSING LA English DT Editorial Material C1 [Moquin, Barbara; Blackman, Marc R.] NCCAM, Div Intramural Res, NIH, Bethesda, MD USA. [Blackman, Marc R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Mitty, Ethel] NYU, Coll Nursing, John A Hartford Inst Geriatr Nursing, New York, NY USA. RP Moquin, B (reprint author), NCCAM, Div Intramural Res, NIH, Bethesda, MD USA. NR 12 TC 7 Z9 7 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4572 J9 GERIATR NURS JI Geriatr. Nurs. PD MAY-JUN PY 2009 VL 30 IS 3 BP 196 EP 203 DI 10.1016/j.gerinurse.2009.03.002 PG 8 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 460YT UT WOS:000267230000007 PM 19520231 ER PT J AU Ren, JS Kamangar, F Qiao, YL Taylor, PR Liang, H Dawsey, SM Liu, B Fan, JH Abnet, CC AF Ren, J-S Kamangar, F. Qiao, Y-L Taylor, P. R. Liang, H. Dawsey, S. M. Liu, B. Fan, J-H Abnet, C. C. TI Serum pepsinogens and risk of gastric and oesophageal cancers in the General Population Nutrition Intervention Trial cohort SO GUT LA English DT Article ID HELICOBACTER-PYLORI INFECTION; CHRONIC ATROPHIC GASTRITIS; SQUAMOUS-CELL CARCINOMA; 2 DISTINCT ETIOLOGIES; CARDIA CANCER; ADENOCARCINOMA; MARKERS; JAPAN; STOMACH; CHINA AB Objective: Low serum pepsinogen I (PGI) and low pepsinogen I/pepsinogen II ratio (PGI/II ratio) are markers of gastric fundic atrophy. We aimed to prospectively test the association between serum PGI/II ratio and risks of gastric non-cardia adenocarcinoma, gastric cardia adenocarcinoma, and oesophageal squamous cell carcinoma (OSCC). Design: Case-cohort study nested in a prospective cohort with over 15 years of follow-up. Setting: Rural region of the People's Republic of China. Subjects: Men and women aged 40-69 years at study baseline. Main outcome measures: Adjusted hazard ratios and 95% confidence intervals for the association between serum PGI/II ratio and cancer risk. Results: Compared to subjects with PGI/II ratio of > 4, those with <= 4 had hazard ratios (HRs) (95% CIs) of 2.72 (1.77 to 4.20) and 2.12 (1.42 to 3.16) for non-cardia and cardia gastric adenocarcinomas, respectively. Risk of both cancers was also increased when we used other cut points ranging from 3 to 6, or quartile models, or nonlinear continuous models. Risk of OSCC was marginally increased in those with PGI/II ratio <= 4, with HR (95% CI) of 1.56 (0.99 to 2.47), but quartile models and continuous models showed no increased risk. The nonlinear continuous models suggested that any single cut point collapsed subjects with dissimilar gastric adenocarcinoma risks, and that using cut points was not an efficient use of data in evaluating these associations. Conclusion: In this prospective study, we found similar and significantly increased risks of non-cardia and cardia gastric adenocarcinomas in subjects with low PGI/II ratio but little evidence for an association with the risk of OSCC. C1 [Kamangar, F.; Taylor, P. R.; Dawsey, S. M.; Abnet, C. C.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Ren, J-S; Qiao, Y-L; Liang, H.; Liu, B.; Fan, J-H] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. [Ren, J-S; Qiao, Y-L; Liang, H.; Liu, B.; Fan, J-H] Peking Union Med Coll, Beijing 100021, Peoples R China. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 3034, Rockville, MD 20852 USA. EM kamangaf@mail.nih.gov; qiaoy@cicams.ac.cn RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU NIH; National Cancer Institute (NCI) [N01-SC-91030, N01-RC-47701, N01-RC-47702]; Cancer Institute; Chinese Academy of Medical Sciences FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, and by NCI contracts number N01-SC-91030, N01-RC-47701 and N01-RC-47702, and by funds from the Cancer Institute, Chinese Academy of Medical Sciences. NR 35 TC 39 Z9 41 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAY PY 2009 VL 58 IS 5 BP 636 EP 642 DI 10.1136/gut.2008.168641 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 431EE UT WOS:000265043300007 PM 19136509 ER PT J AU Franchelli, S Leone, MS Bruzzone, M Muggianu, M Puppo, A Gustavino, C Di Capua, E Centurioni, MG AF Franchelli, S. Leone, M. S. Bruzzone, M. Muggianu, M. Puppo, A. Gustavino, C. Di Capua, E. Centurioni, M. G. TI The gluteal fold fascio-cutaneous flap for reconstruction after radical excision of primary vulvar cancers SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Gynecological surgery; Vulvar cancer; Vulvar reconstruction; Gluteal fold fascio-cutaneous flap; Vulvectomy ID VAGINAL RECONSTRUCTION; BREAST RECONSTRUCTION; MYOCUTANEOUS FLAPS; CARCINOMA; SURGERY AB Objectives. Reconstructive surgery plays an important role in cosmetic and functional results of major excisional Surgery performed as a treatment for invasive vulvar cancer. Traditional techniques - gracilis myocutaneous o rectus abdominis flaps - have several limits. We describe here a different surgical approach that we have used since 1998 in an effort to obtain better results in vulvar reconstruction. Methods. From January 1998 to June 2007, thirty three patients who underwent excisional radical surgery for invasive vulvar tumors, were treated with vulvar reconstruction using the gluteal fold fascio-cutaneous local flap. Flaps were designed along the gluteal fold in adequate length and size. They were oval or triangular in shape depending on the defect they were supposed to cover. The flaps - which always included the fascial layer - were raised up to identify a perforator branch of the internal pudendal artery and then harvested as an island flap to achieve better mobility. Results. We had no major complications, only two patients presented marginal necrosis and eight patients experienced significant seromas. Advantages over the alternative techniques included reduced dimensions of scars, absence of flap liponecrosis, no need of modifying patient's position on the surgical table, and very limited blood loss. Conclusions. We conclude that gluteal fold flap offers excellent cosmetic and functional results with a low complication rate. Therefore we support the gluteal fold flap as a valid surgical option whenever reconstruction is needed after radical excision of vulvar neoplasms. (C) 2009 Elsevier Inc. All rights reserved. C1 [Puppo, A.; Gustavino, C.; Di Capua, E.; Centurioni, M. G.] Natl Canc Inst, Gynecol Oncol Unit, I-16132 Genoa, Italy. [Franchelli, S.; Leone, M. S.; Muggianu, M.] Natl Canc Inst, Plast & Reconstruct Surg Unit, I-16132 Genoa, Italy. [Bruzzone, M.] Natl Canc Inst, Med Oncol Unit, I-16132 Genoa, Italy. RP Centurioni, MG (reprint author), Natl Canc Inst, Gynecol Oncol Unit, Largo R Benzi 10, I-16132 Genoa, Italy. EM mariagrazia.centurioni@istge.it NR 15 TC 13 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2009 VL 113 IS 2 BP 245 EP 248 DI 10.1016/j.ygyno.2009.01.017 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 436GJ UT WOS:000265400400019 PM 19251311 ER PT J AU Goldin, LR Bjorkholm, M Kristinsson, SY Turesson, I Landgren, O AF Goldin, Lynn R. Bjorkholm, Magnus Kristinsson, Sigurdur Y. Turesson, Ingemar Landgren, Ola TI Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin's lymphomas among relatives of patients with chronic lymphocytic leukemia SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE chronic lymphocytic leukemia; non-Hodgkin's lymphoma; familial risk ID POPULATION-BASED SAMPLES; B-CELL LYMPHOCYTOSIS; FAMILIAL AGGREGATION; WALDENSTROM MACROGLOBULINEMIA; LYMPHOPROLIFERATIVE TUMORS; 1ST-DEGREE RELATIVES; SUSCEPTIBILITY LOCI; CANCER; ANTICIPATION; CLASSIFICATION AB Background Previous Studies have shown increased familial risk for chronic lymphocytic leukemia. In the most comprehensive study to date, we evaluated risk of chronic lymphocytic leukemia and lymphoproliferative disorders among First-degree relatives of chronic lymphocytic leukemia cases compared to first-degree relatives of controls. Design and Methods Population-based registry data from Sweden were used to evaluate outcomes in 26,947 first-degree relatives of 9,717 chronic lymphocytic leukemia patients (diagnosed 19583 8,159 matched controls. Using a 2004) compared with 107,223 first-degree relatives of 1 as marginal survival model, we calculated relative risks (RR) and 95% confidence intervals measures of Familial aggregation. Results Compared to relatives of controls, relatives of chronic lymphocytic leukemia patients had an increased risk for chronic lymphocytic leukemia (RR=8.5, 6.1-11.7) and other non-Hodkin's lymphomas (NHLs) (RR=1.9, 1.5-2.3). Evaluating NHL subtypes, we found a striking excess of indolent B-cell NHL specifically lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia and hairy cell leukemia. No excesses of aggressive B-cell or T-cell lymphomas were found. There was no statistical excess of Hodgkin's lymphoma, multiple myeloma, or the precursor condition, monoclonal gammopathy of undetermined significance, among chronic lymphocytic leukemia relatives. Conclusions These familial aggregations are striking and provide novel clues to research designed to uncover early pathogenetic mechanisms in chronic lymphocytic leukemia including studies to identify germ line susceptibility genes. However, clinicians should counsel their chronic lymphocytic leukemia patients emphasizing that because the baseline population risks are low, the absolute risk for a first-degree relative to develop chronic lymphocytic leukemia or another indolent lymphoma is low. At this time, an increased medical surveillance of first-degree relatives of chronic lymphocytic leukemia patients has no role Outside research studies. C1 [Goldin, Lynn R.; Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Bjorkholm, Magnus; Kristinsson, Sigurdur Y.; Landgren, Ola] Karolinska Univ, Hosp Solna, Div Hematol, Dept Med, Stockholm, Sweden. [Bjorkholm, Magnus; Kristinsson, Sigurdur Y.; Landgren, Ola] Karolinska Inst, Stockholm, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Intramural Research Program of the NIH; NCI; Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations FX Funding: this research was supported by the Intramural Research Program of the NIH, NCI and by grants from the Swedish Cancer Society, Stockholm County Council, and the Karolinska Institutet Foundations. NR 35 TC 56 Z9 57 U1 0 U2 2 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD MAY PY 2009 VL 94 IS 5 BP 647 EP 653 DI 10.3324/haematol.2008.003632 PG 7 WC Hematology SC Hematology GA 445JH UT WOS:000266046600009 PM 19286886 ER PT J AU Wang, PS Ulbricht, CM Schoenbaum, M AF Wang, Philip S. Ulbricht, Christine M. Schoenbaum, Michael TI Improving Mental Health Treatments Through Comparative Effectiveness Research SO HEALTH AFFAIRS LA English DT Article; Proceedings Paper CT Institute-of-Medicine Roundtable on Evidence-Based Medicine CY DEC, 2007 CL Washington, DC SP Inst Med ID ATYPICAL ANTIPSYCHOTIC MEDICATIONS; RANDOMIZED CONTROLLED-TRIAL; UNITED-STATES; COST-EFFECTIVENESS; 2ND-GENERATION ANTIPSYCHOTICS; CHRONIC-SCHIZOPHRENIA; CARE; DRUGS; DEPRESSION; POLICY AB There is a pressing need for comparative effectiveness research to improve mental health treatments. Although U. S. mental health spending has increased dramatically, mainly because of the rapid adoption of newer psychotropic medications, fewer than a quarter of people with serious mental illnesses receive appropriate care. Because of a general lack of information on the relative effectiveness of different treatments, payers are uncertain about the value of current spending, which in turn may deter new investments to reduce unmet need. We use several recent comparative effectiveness trials to illustrate the potential value of such research for improving practice and policy. [Health Affairs 28, no. 3 (2009): 783-791; 10.1377/hlthaff.28.3.783] C1 [Wang, Philip S.; Ulbricht, Christine M.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Schoenbaum, Michael] NIMH, Mental Hlth Serv, Bethesda, MD 20892 USA. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. EM wangphi@mail.nih.gov NR 43 TC 15 Z9 16 U1 1 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2009 VL 28 IS 3 BP 783 EP 791 DI 10.1377/hlthaff.28.3.783 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 441OV UT WOS:000265779400020 PM 19414887 ER PT J AU Pearson, SD Lieber, SR AF Pearson, Steven D. Lieber, Sarah R. TI Financial Penalties For The Unhealthy? Ethical Guidelines For Holding Employees Responsible For Their Health SO HEALTH AFFAIRS LA English DT Article AB As health care costs continue to rise, an increasing number of self-insured employers are using financial rewards or penalties to promote healthy behavior and control costs. These incentive programs have triggered a backlash from those concerned that holding employees responsible for their health, particularly through the use of penalties, violates individual liberties and discriminates against the unhealthy. This paper offers an ethical analysis of employee health incentive programs and presents an argument for a set of conditions under which penalties can be used in an ethical and responsible way to contain health care costs and encourage healthy behavior among employees. [Health Affairs 28, no. 3 (2009): 845-852; 10.1377/hlthaff.28.3.845] C1 [Pearson, Steven D.] Massachusetts Gen Hosp, Inst Clin & Econ Review, Boston, MA 02114 USA. RP Pearson, SD (reprint author), NIH, Ctr Clin, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM spearson@icer-review.org; Lieber@post.harvard.edu FU National Institutes of Health (NIH) FX This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH). The opinions expressed are the authors' own. They do not represent any position or policy of the NIH, Public Health Service, or Department of Health and Human Services. NR 20 TC 22 Z9 23 U1 0 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2009 VL 28 IS 3 BP 845 EP 852 DI 10.1377/hlthaff.28.3.845 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 441OV UT WOS:000265779400030 PM 19414897 ER PT J AU Buetow, KH Niederhuber, J AF Buetow, Kenneth H. Niederhuber, John TI Infrastructure For A Learning Health Care System: CaBIG SO HEALTH AFFAIRS LA English DT Letter C1 [Buetow, Kenneth H.; Niederhuber, John] NCI, Bethesda, MD 20892 USA. RP Buetow, KH (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2009 VL 28 IS 3 BP 923 EP 924 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 441OV UT WOS:000265779400044 PM 19414908 ER PT J AU Strech, D Persad, G Marckmann, G Danis, M AF Strech, Daniel Persad, Govind Marckmann, Georg Danis, Marion TI Are physicians willing to ration health care? Conflicting findings in a systematic review of survey research SO HEALTH POLICY LA English DT Review DE Healthcare rationing; Bedside rationing; Physicians' attitudes; Systematic review; Survey research; Bioethics ID US NEUROLOGISTS; MANAGED CARE; ATTITUDES; COST; PATIENT; EXPLANATION; CONSTRAINTS; PERCEPTIONS; MEDICATIONS; BARRIERS AB Background: Several quantitative surveys have been conducted internationally to gather empirical information about physicians' general attitudes towards health care rationing. Are physicians ready to accept and implement rationing, or are they rather reluctant? Do they prefer implicit bedside rationing that allows the physician-patient relationship broad leeway in individual decisions? Or do physicians prefer strategies that apply explicit criteria and rules? Objectives: To analyse the range of survey findings on rationing. To discuss differences in response patterns. To provide recommendations for the enhancement of transparency and systematic conduct in reviewing survey literature. Methods: A systematic search was performed for all English and non-English language references using CINAHL, EMBASE, and MEDLINE. Three blinded experts independently evaluated title and abstract of each reference. Survey items were extracted that match with: (i) willingness to ration health care or (ii) preferences for different rationing strategies. Results: 16 studies were eventually included in the systematic review. Percentages of respondents willing to accept rationing ranged from 94% to 9%. Conclusions: The conflicting findings among studies illustrate important ambivalence in physicians that has several implications for health policy. Moreover, this review highlights the importance to interpret survey findings in context of the results of all previous relevant studies. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Strech, Daniel] Hannover Med Sch, Ctr Publ Hlth & Healthcare, Inst Hist Eth & Philosophy Med, D-30625 Hannover, Germany. [Strech, Daniel; Persad, Govind; Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA. [Marckmann, Georg] Univ Tubingen, Inst Eth & Hist Med, D-72074 Tubingen, Germany. RP Strech, D (reprint author), Hannover Med Sch, Ctr Publ Hlth & Healthcare, Inst Hist Eth & Philosophy Med, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM strech.daniel@mh-hannover.de OI Strech, Daniel/0000-0002-9153-079X FU German Federal Ministry of Education and Research [01GP0608]; German Academic Exchange Service FX Funding: Supported in part by grant 01GP0608 from the German Federal Ministry of Education and Research and a grant for Daniel Strech from the German Academic Exchange Service. NR 37 TC 34 Z9 35 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD MAY PY 2009 VL 90 IS 2-3 BP 113 EP 124 DI 10.1016/j.healthpol.2008.10.013 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 444RL UT WOS:000265998000001 PM 19070396 ER PT J AU Park, O Jeong, WI Wang, L Wang, H Lian, ZX Gershwin, ME Gao, B AF Park, Ogyi Jeong, Won-Il Wang, Lei Wang, Hua Lian, Zhe-Xiong Gershwin, M. Eric Gao, Bin TI Diverse Roles of Invariant Natural Killer T Cells in Liver Injury and Fibrosis Induced by Carbon Tetrachloride SO HEPATOLOGY LA English DT Article ID HEPATIC STELLATE CELLS; PRIMARY BILIARY-CIRRHOSIS; INNATE IMMUNE-SYSTEM; NKT CELLS; MICE; ACTIVATION; FIBROGENESIS; ALPHA; INFLAMMATION; REGENERATION AB Liver fibrosis is a common scarring response to all forms of chronic liver injury and is always associated with inflammation that contributes to fibrogenesis. Although a variety of cell populations infiltrate the liver during inflammation, it is generically clear that CD8 T lymphocytes promote while natural killer (NK) cells inhibit liver fibrosis. However, the role of invariant natural killer T (iNKT) cells, which are abundant in the liver, in hepatic fibrogenesis, remains obscure. Here we show that iNKT-deficient mice are more susceptible to carbon tetrachloride (CCl(4))-induced acute liver injury and inflammation. The protective effect of naturally activated iNKT in this model is likely mediated via suppression of the proinflammatory effect of activated hepatic stellate cells. Interestingly, strong activation of iNKT through injection of iNKT activator alpha-galactosylceramide (alpha-Galcer) accelerates CCl(4)-induced acute liver injury and fibrosis. In contrast, chronic CCl(4) administration induces a similar degree of liver injury in iNKT-deficient and wild-type mice, and only a slightly higher grade of liver fibrosis in iNKT-deficient mice than wild-type mice 2 weeks but not 4 weeks after CCl(4) injection, although iNKT cells are able to kill activated stellate cells. An insignificant role of iNKT in chronic liver injury and fibrosis may be attributable to hepatic iNKT cell depletion. Finally, chronic alpha-GalCer treatment had little effect on liver injury and fibrosis, which is attributable to iNKT tolerance after alpha-GalCer injection. Conclusion: Natural activation of hepatic iNKT cells inhibits, whereas strong activation of iNKT cells by alpha-GalCer accelerates CCl(4)-induced acute liver injury, inflammation, and fibrosis. During chronic liver injury, hepatic iNKT cells are depleted and play a role in inhibiting liver fibrosis in the early stage but not the late stage of fibrosis. (HEPATOLOGY 2009;49:1683-1694.) C1 [Park, Ogyi; Jeong, Won-Il; Wang, Lei; Wang, Hua; Gao, Bin] NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Lian, Zhe-Xiong; Gershwin, M. Eric] Univ Calif Davis, Div Rheumatol, Davis, CA 95616 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI JEONG, WON IL/B-6615-2011 FU National Institute on Alcohol Abuse and Alcoholism; National Institutes of Health FX This work was supported by The Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 45 TC 87 Z9 93 U1 1 U2 18 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP 1683 EP 1694 DI 10.1002/hep.22813 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZX UT WOS:000265668500032 PM 19205035 ER PT J AU Doo, EC Hoofnagle, JH AF Doo, Edward C. Hoofnagle, Jay H. TI The Hepatitis B Research Network SO HEPATOLOGY LA English DT Editorial Material C1 [Doo, Edward C.; Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Doo, EC (reprint author), Room 651,Democracy 2,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM DooE@niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP S196 EP S197 DI 10.1002/hep.22953 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700023 PM 19399805 ER PT J AU Doo, EC Hoofnagle, JH Rodgers, GP AF Doo, Edward C. Hoofnagle, Jay H. Rodgers, Griffin P. TI NIH Consensus Development Conference: Management of Hepatitis B October 20-22, 2008 Introduction SO HEPATOLOGY LA English DT Editorial Material ID WORKSHOP C1 [Doo, Edward C.] NIDDK, Liver Dis Res Program, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Rodgers, Griffin P.] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA. RP Doo, EC (reprint author), NIDDK, Liver Dis Res Program, Liver Dis Res Branch, NIH, 2 Democracy Plaza,Room 651,MSC 5450,6707 Democrac, Bethesda, MD 20892 USA. EM Dooe@niddk.nih.gov NR 6 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP S1 EP S3 DI 10.1002/hep.22993 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700001 PM 19399814 ER PT J AU Ghany, MG Doo, EC AF Ghany, Marc G. Doo, Edward C. TI Antiviral Resistance and Hepatitis B Therapy SO HEPATOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Management of Hepatitis B Virus CY OCT 20-22, 2008 CL Bethesda, MD SP Natl Inst Hlth ID TENOFOVIR DISOPROXIL FUMARATE; PROLONGED LAMIVUDINE THERAPY; ADEFOVIR DIPIVOXIL THERAPY; VIRUS POLYMERASE MUTATIONS; NUCLEOSIDE-NAIVE PATIENTS; HBEAG-NEGATIVE PATIENTS; ENTECAVIR RESISTANCE; DRUG-RESISTANCE; IN-VITRO; HBV POLYMERASE AB The management of chronic hepatitis B currently rests with long-term therapy using oral nucleoside analogs. The major limitation of long-term therapy is antiviral resistance. Antiviral resistance is due to the high rate of mutations that can occur during hepatitis B virus (HBV) replication and the selection of these mutants due to a replication advantage in the presence of the antiviral agent. Indeed, high rates of antiviral resistance have been found with long-term use of lamivudine, in up to 76% of patients treated for 5 years or more. Rates of antiviral resistance are lower with adefovir therapy, similar to 30% at 5 years. Newer more potent nucleoside analogs (tenofovir and entecavir) have proven to have much lower rates of antiviral resistance (<1% after 2 years in treatment-naive subjects) I but the long-term rates of resistance have yet to be fully defined. The appearance of these viral mutations (genotypic resistance) is usually followed by rises in HBV DNA levels (virological breakthrough) and then by rises in serum aminotransferase levels (biochemical breakthrough). The appearance of antiviral resistance can be accompanied by a transient but occasionally severe exacerbation of the underlying liver disease which in some instances has led to acute liver failure. Combinations of nucleoside analogs may offer an approach to preventing antiviral resistance, but the efficacy and safety of this approach have yet to be shown. A future research priority is to identify new agents active against HBV that target different steps in the viral life-cycle and might provide effective means to circumvent the antiviral resistance of nucleoside analogs. (HEPATOLOGY 2009;49:S174-S184.) C1 [Ghany, Marc G.] NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. [Doo, Edward C.] NIDDK, Liver Dis Res Program, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, Div Digest Dis & Nutr, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM Marcg@intra.niddk.nih.gov FU Intramural NIH HHS [Z01 DK054517-01] NR 84 TC 111 Z9 119 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 SU S BP S174 EP S184 DI 10.1002/hep.22900 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700021 PM 19399794 ER PT J AU Hoofnagle, JH AF Hoofnagle, Jay H. TI Reactivation of Hepatitis B SO HEPATOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Management of Hepatitis B Virus CY OCT 20-22, 2008 CL Bethesda, MD SP Natl Inst Hlth ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; ANTIBODY-POSITIVE DONORS; LOW-DOSE METHOTREXATE; NON-HODGKINS-LYMPHOMA; ORTHOTOPIC LIVER-TRANSPLANTATION; PREEMPTIVE LAMIVUDINE THERAPY; VIRUS HBV REACTIVATION; SURFACE-ANTIGEN; CORE ANTIBODY AB Reactivation of hepatitis B refers to the abrupt increase in hepatitis B virus (HBV) replication in a patient with inactive or resolved hepatitis B. Reactivation can occur spontaneously, but more typically is triggered by immunosuppressive therapy of cancer, autoimmune disease, or organ transplantation. Reactivation can be transient and clinically silent, but often causes a flare of disease that can be severe resulting in acute hepatic failure. Most instances of reactivation resolve spontaneously, but if immune suppression is continued, re-establishment of chronic hepatitis occurs which can lead to progressive liver injury and cirrhosis. The best-described instances of reactivation occur in hepatitis B surface antigen (HBsAg) carriers with inactive or minimally active disease who are given cancer chemotherapy for lymphoma or leukemia. Typically, serum HBV DNA rises during chemotherapy, followed by a disease flare and HBV DNA clearance with immune reconstitution after chemotherapy is stopped. Special forms of reactivation occur after solid organ and bone marrow transplantation in which chronic infection often results. Several randomized, placebo-controlled trials have shown that reactivation can be prevented by antiviral prophylaxis. Routine prophylaxis is therefore recommended for persons with HBsAg undergoing cancer chemotherapy or transplantation, but major questions remain. Which patients should be screened for HBsAg and should all be treated? Which antiviral should be used and for how long? Should persons with resolved hepatitis B without HBsAg receive prophylaxis? Future research should address the underlying molecular mechanisms of reactivation as well as its optimal means of diagnosis, treatment, and prevention in different patient populations. (HEPATOLOGY 2009; 49:S156-S165.) C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov NR 91 TC 200 Z9 216 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP S156 EP S165 DI 10.1002/hep.22945 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700019 PM 19399803 ER PT J AU Liang, TJ AF Liang, T. Jake TI Hepatitis B: The Virus and Disease SO HEPATOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Management of Hepatitis B Virus CY OCT 20-22, 2008 CL Bethesda, MD SP Natl Inst Hlth ID SURFACE-ANTIGEN; VIRAL-HEPATITIS; HEPATOCELLULAR-CARCINOMA; MEMBRANOUS NEPHROPATHY; REPLICATION STRATEGY; NATURAL-HISTORY; GENE-EXPRESSION; S-GENE; INFECTION; LIVER AB Hepatitis B virus (HBV) infects more than 300 million people worldwide and is a common cause of liver disease and liver cancer. HBV, a member of the Hepadnaviridae family, is a small DNA virus with unusual features similar to retroviruses. HBV replicates through an RNA intermediate and can integrate into the host genome. The unique features of the HBV replication cycle confer a distinct ability of the virus to persist in infected cells. Virological and serological assays have been developed for diagnosis of various forms of HBV-associated disease and for treatment of chronic hepatitis B infection. HBV infection leads to a wide spectrum of liver disease ranging from acute (including fulminant hepatic failure) to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Acute HBV infection can be either asymptomatic or present with symptomatic acute hepatitis. Most adults infected with the virus recover, but 5%-10% are unable to dear the virus and become chronically infected. Many chronically infected persons have mild liver disease with little or no long-term morbidity or mortality. Other individuals with chronic HBV infection develop active disease, which can progress to cirrhosis and liver cancer. These patients require careful monitoring and warrant therapeutic intervention. Extrahepatic manifestations of HBV infection are rare but can be difficult to diagnose and manage. The challenges in the area of HBV-associated disease are the lack of knowledge in predicting outcome and progression of HBV infection and an unmet need to understand the molecular, cellular, immunological, and genetic basis of various disease manifestations associated with HBV infection. (REPATOLOGY 2009;49: S13-S21.) C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 DK054500-11, Z01 DK054500-12, Z01 DK054501-11, Z01 DK054501-12, Z99 DK999999, ZIA DK054500-13] NR 63 TC 177 Z9 194 U1 2 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP S13 EP S21 DI 10.1002/hep.22881 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700003 PM 19399811 ER PT J AU Mani, H Kleiner, DE AF Mani, Haresh Kleiner, David E. TI Liver Biopsy Findings in Chronic Hepatitis B SO HEPATOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Management of Hepatitis B Virus CY OCT 20-22, 2008 CL Bethesda, MD SP Natl Inst Hlth ID FIBROSING CHOLESTATIC HEPATITIS; CHRONIC VIRAL-HEPATITIS; ALANINE AMINOTRANSFERASE LEVELS; HISTOLOGY ACTIVITY INDEX; PERSISTENTLY NORMAL ALT; VIRUS PRECORE MUTANT; LARGE-CELL CHANGE; HEPATOCELLULAR-CARCINOMA; E-ANTIGEN; CORE ANTIGEN AB Liver biopsy plays a central role in treatment algorithms in patients with hepatitis B and remains the gold standard for evaluating hepatic pathology. The pathology of hepatitis B is diverse and reflects the natural history of infection. An acute hepatitic pattern with lobular disarray is seen in acute infection, during acute flares of disease, and with acute hepatitis D superinfection. In chronic hepatitis B, inflammation is less pronounced in the immune-tolerant phase and is prominent during immune-mediated viral clearance. Active inflammation appears to be the driving force for development of fibrosis. Inflammatory grades and fibrosis stage are assigned as is done for hepatitis C. Although current management guidelines recommend liver biopsies only in select patients based on age, viral levels, and hepatitis B e antigen status, these clinical and biochemical parameters do not show consistent correlations with liver histology. Liver biopsy also helps identify preneoplastic lesions including large cell and small cell change. Unlike in other causes of chronic hepatitis, immunostains are widely used and can help determine the phase of infection. Liver biopsies can also identify additional pathology that may contribute to liver disease such as steatohepatitis, iron overload, autoimmune hepatitis, and drug-induced injury. Thus, liver biopsy can play an important role in staging and grading chronic hepatitis B and should be more widely used in assessing the need for therapy. (HEPATOLOGY 2009;49:S61-S71.) C1 [Mani, Haresh; Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Kleiner, DE (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2B50,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM kleinerd@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 108 TC 43 Z9 47 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 SU S BP S61 EP S71 DI 10.1002/hep.22930 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700009 PM 19399798 ER PT J AU Rotman, Y Brown, TA Hoofnagle, JH AF Rotman, Yaron Brown, Thomas A. Hoofnagle, Jay H. TI Evaluation of the Patient with Hepatitis B SO HEPATOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Management of Hepatitis B Virus CY OCT 20-22, 2008 CL Bethesda, MD SP Natl Inst Hlth ID NATURAL-HISTORY; LIVER FIBROSIS; SURFACE-ANTIGEN; VIRUS-INFECTION; LAMIVUDINE; DISEASE; MARKERS; AMINOTRANSFERASE; DETERMINANTS; TRANSMISSION AB The initial evaluation of a patient with hepatitis B virus infection should attempt to assess the disease activity and stage in the context of the known natural history of this infection and to properly assess the needs for treatment and surveillance. In addition to a medical history and focused physical examination, the initial evaluation usually requires serological, biochemical, and virological tests to confirm the diagnosis as well as an imaging study to establish a baseline for future monitoring. A liver biopsy is generally not needed but can provide useful information on prognosis, need for surveillance for hepatocellular carcinoma (HCC), and whether to recommend therapy. Follow-up monitoring is aimed at determining disease progression, development of complications, and reassessing the need for treatment. Monitoring frequency should be determined based on the activity and stage of disease. Initiation of screening for HCC should be based on age, race, sex, family history, and stage and duration of disease. The current recommended method of screening and surveillance for HCC is by ultrasonography and alpha-fetoprotein measurements every 6-12 months. Prospective studies are needed to evaluate the role of longitudinal application of noninvasive assays of fibrosis, such as serum fibrosis markers and transient elastography. Better biomarkers and imaging modalities are needed for early detection of HCC. Finally, studies are needed to better refine the indications and to balance the risks and benefits of antiviral therapy. (HEPATOLOGY 2009;49:S22-S27.) C1 [Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, CRC, Bethesda, MD 20892 USA. [Brown, Thomas A.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. RP Rotman, Y (reprint author), NIDDK, Liver Dis Branch, NIH, CRC, Room 4-5722,10 Ctr Dr, Bethesda, MD 20892 USA. EM rotmany@mail.nih.gov OI Rotman, Yaron/0000-0002-7549-8216 FU Intramural NIH HHS [Z99 DK999999] NR 30 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 2009 VL 49 IS 5 BP S22 EP S27 DI 10.1002/hep.22976 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439ZZ UT WOS:000265668700004 PM 19399815 ER PT J AU Wohl, DA Kendall, MA Andersen, J Crumpacker, C Spector, SA Feinberg, J Alston-Smith, B Owens, S Chafey, S Marco, M Maxwell, S Lurain, N Jabs, D Benson, C Keiser, P Jacobson, MA AF Wohl, D. A. Kendall, M. A. Andersen, J. Crumpacker, C. Spector, S. A. Feinberg, J. Alston-Smith, B. Owens, S. Chafey, S. Marco, M. Maxwell, S. Lurain, N. Jabs, D. Benson, C. Keiser, P. Jacobson, M. A. CA A5030 Study Team TI Low Rate of CMV End-Organ Disease in HIV-Infected Patients Despite Low CD4+Cell Counts and CMV Viremia: Results of ACTG Protocol A5030 SO HIV CLINICAL TRIALS LA English DT Article DE AIDS; CMV; opportunistic disease prevention; valganciclovir ID IMMUNODEFICIENCY VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; CYTOMEGALOVIRUS CMV; RISK-FACTORS; DNA LOAD; AIDS; SURVIVAL AB Purpose: To describe cytomegalovirus (CMV) end-organ disease (EOD) rate in AIDS patients with low CD4+ cell count despite HAART who were enrolled in a randomized, placebo-controlled trial of preemptive valganciclovir (VGCV) to prevent CMV EOD in those with CMV viremia. Methods: Subjects (N = 338) were HIV-infected with CD4+ count <100 cells/mm(3), plasma HIV RNA >400 copies/mL, and on stable or no HAART All underwent plasma CMV DNA PCR testing every 8 weeks (Step 1); those with detectable CMV DNA were randomized to VGCV or placebo (Step 2). Results: Plasma CMV DNA was detected in 68 (20%), of whom 4 developed CMV EOD. During Step 1, 53 died. Of the 47 who entered Step 2 (24 VGCV, 23 placebo), CMV EOD was diagnosed in 10 (4 VGCV, 6 placebo) and 15 died (7 VGCV, 8 placebo). Of those randomized to placebo, 14% were diagnosed with CMV EOD at 12 months. Conclusions: We observed a lower CMV EOD rate among subjects receiving HAART than predicted based on published literature. However, mortality was high in this study. Our findings suggest that preemptive anti-CMV therapy in patients with persistently low CD4+ cell counts in the current treatment era may not be warranted given the low incidence of CMV EOD and high all-cause mortality observed in this study population. C1 [Wohl, D. A.] Univ N Carolina, AIDS Clin Trials Unit, Chapel Hill, NC 27599 USA. [Kendall, M. A.; Andersen, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Crumpacker, C.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Spector, S. A.; Benson, C.] Univ Calif San Diego, San Diego, CA 92103 USA. [Feinberg, J.] Univ Cincinnati, Cincinnati, OH USA. [Alston-Smith, B.] NIH, Div AIDS, Bethesda, MD 20892 USA. [Owens, S.] Frontier Sci & Technol Fdn, Amherst, NY USA. [Chafey, S.] Univ Calif Los Angeles, Los Angeles, CA USA. [Marco, M.] Columbia Univ, New York, NY USA. [Maxwell, S.] Univ Washington, Seattle, WA USA. [Lurain, N.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Jabs, D.] Mt Sinai Sch Med, New York, NY USA. [Keiser, P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Jacobson, M. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Wohl, DA (reprint author), Univ N Carolina, AIDS Clin Trials Unit, Campus Box 7215, Chapel Hill, NC 27599 USA. EM wohl@med.unc.edu RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU National Institute of Allergy and Infectious Diseases [A168636, AI68634, AI69432, AI46376, AI69450, AI 69513-01, AI69423-01, AI69439, AI32783-13, AI069556, AI27660, AI069502-01, AI069434, AI27664, AI46370, AI69532-01, AI69411, AI69494-01, AI69474, AI069501, AI34853, AI27659, AI27661, AI69495, AI 69471, AI46381, AI32782, AI69470-01]; National Center for Research Resources [RR00051, RR00046, M01-RR00096]; University of North Carolina CFAR [AI50410]; University of Pennsylvania CFAR [5-P30-AI-045008-07] FX Additional support was provided by the University of North Carolina CFAR Grant AI50410 and University of Pennsylvania CFAR Grant 5-P30-AI-045008-07. Participating A5030 sites: J. Hoffman, S. Cahill (UC San Diego Medical Center); T Petersen, P. Keiser (UT Southwestern Medical Center); B. Putnam, R. Levinson (University of Colorado Health Sciences Center); J. Feinberg, J. Baer (University of Cincinnati); C. Zelasky, S. Pedersen (University of North Carolina); J. Nicotera, V. Bailey (Vanderbilt University); C. Nichols, J. Quinn (University of Pennsylvania, Philadelphia); J. Norris, S. Valle (Stanford University); A. Moe, A. Johiro (UCLA Medical Center); M. Jacobson, J. Volinski (San Francisco General Hospital); S. Storey, J. Schouten, (University of Washington); D. Mildvan, M. Revuelta (Beth Israel Medical Center); R. Hutt, M. Vasquez (NYU/NYC HHC at Bellevue); C Greisberger, R Reichman, (Rochester University); S. Riddler, B. Rutecki (University of Pittsburgh); S. L. Koletar, D. Gochnour (Ohio State University); R.A. Salata, P. Walton (Case Western Reserve University); University of Hawaii at Manoa, Leahi; Harvard; Massachusetts General Hospital; University of Minnesota; M. Rodriguez, L. Kessels (Washington University); K. Coleman, A. Lyons (Northwestern University); K.T. Tashima, H. Sousa (Miriam Hospital); W.A. O'Brien, C. Mogridge (University of Texas, Galveston); J. Noel Connor, M. Crawford (Columbia Collaborative HIV/AIDS Clinical Trials Unit); University of Southern California; Methodist Hospital of Indiana; M. Palmore, E. R. Patrick (Emory University); and H.H. Bolivar, M.A. Fischl (University of Miami). NR 14 TC 18 Z9 22 U1 0 U2 0 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAY-JUN PY 2009 VL 10 IS 3 BP 143 EP 152 DI 10.1310/hct1003-143 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 471SP UT WOS:000268078900003 PM 19632953 ER PT J AU Thornton, J Zehr, JL Loose, MD AF Thornton, Jan Zehr, Julia L. Loose, Michael D. TI Effects of prenatal androgens on rhesus monkeys: A model system to explore the organizational hypothesis in primates SO HORMONES AND BEHAVIOR LA English DT Review DE Organizational hypothesis; Nonhuman primates; Rhesus monkeys; Prenatal androgens; Sex differences; Juvenile behavior; Adult sexual behavior ID POLYCYSTIC-OVARY-SYNDROME; CONGENITAL ADRENAL-HYPERPLASIA; GENDER-RELATED BEHAVIOR; FEMALE SEXUAL-BEHAVIOR; IN-VITRO FERTILIZATION; MACACA-MULATTA; TESTOSTERONE PROPIONATE; SOCIAL-BEHAVIOR; ADULT MALE; PSEUDOHERMAPHRODITIC RHESUS AB After proposing the organizational hypothesis from research in prenatally androgenized guinea pigs (Phoenix, C.H., Goy, R.W., Gerall, A.A., Young, W.C., 1959. Organizational action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65, 369-382.), the same authors almost immediately extended the hypothesis to a nonhuman primate model, the rhesus monkey. Studies over the last 50 years have verified that prenatal androgens have permanent effects in rhesus monkeys on the neural circuits that underlie sexually dimorphic behaviors. These behaviors include both sexual and social behaviors, all of which are also influenced by social experience. Many juvenile behaviors such as play, mounting, and vocal behaviors are masculinized and/or defeminized, and aspects of adult sexual behavior are both masculinized (e.g. approaches, sex contacts, and mounts) and defeminized (e.g. sexual solicits). Different behavioral endpoints have different periods of maximal susceptibility to the organizing actions of prenatal androgens. Aromatization is not important, as both testosterone and dihydrotestosterone are equally effective in rhesus monkeys. Although the full story of the effects of prenatal androgens on sexual and social behaviors in the rhesus monkey has not yet completely unfolded, much progress has been made. Amazingly, a large number of the inferences drawn from the original 1959 study have proved applicable to this nonhuman primate model. (C) 2009 Elsevier Inc. All rights reserved. C1 [Thornton, Jan; Loose, Michael D.] Oberlin Coll, Dept Neurosci, Oberlin, OH 44074 USA. [Thornton, Jan] Oberlin Coll, Dept Biol, Oberlin, OH 44074 USA. [Zehr, Julia L.] NIMH, Div Dev Translat Res, Bethesda, MD 20892 USA. RP Thornton, J (reprint author), Oberlin Coll, Dept Neurosci, 119 Woodland St, Oberlin, OH 44074 USA. EM jan.thornton@oberlin.edu FU NIMH; NIH; HHS; United States government FX The views expressed in this article do not necessarily represent the views of the NIMH, NIH, HHS, or the United States government. NR 132 TC 38 Z9 38 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD MAY PY 2009 VL 55 IS 5 BP 633 EP 644 DI 10.1016/j.yhbeh.2009.03.015 PG 12 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 454VQ UT WOS:000266711500011 PM 19446080 ER PT J AU Kim, Z Kim, MJ Kim, JH Jin, SY Kim, YB Seo, D Choi, D Hur, KY Kim, JJ Lee, MH Moon, C AF Kim, Zisun Kim, Min Joo Kim, Jung Hoon Jin, So Young Kim, Yong Bae Seo, Daekwan Choi, Dongho Hur, Kyung Yul Kim, Jae Joon Lee, Min Hyuk Moon, Chul TI Prediction of post-operative pancreatic fistula in pancreaticoduodenectomy patients using pre-operative MRI: a pilot study SO HPB LA English DT Article DE Post-operative pancreatic fistula; magnetic resonance imaging; pancreaticoduodenectomy AB Background: Post-operative pancreatic fistula (POPF) is one of the most fearful complications which may occur after pancreaticoduodenectomy (PD). The methods used to predict POPF pre-operatively have not been studied in great detail. We analyzed correlation between various parameters related to PD including pre-operative magnetic resonance imaging (MRI) signal intensity (SI), pathology of pancreatic fibrosis and occurrence rates of POPF, and verified that MRI SI results could be the determining values for pre-operative prediction of POPF. Methods: From January 2005 to August 2006, we retrospectively examined 43 cases of PDs by reviewing abdominal MRI findings, degree of fibrosis of remnant pancreatic stump, and other surgery-related parameters. Results: POPF encountered in PD were 11 cases (25.6%). Operation time and degree of fibrosis of remnant pancreatic cut surface were related to POPF (P = 0.030, P = 0.010). The pancreas-liver SI ratio (PLSI) between fistula group and no fistula group was -0.0009 +/- 0.2 and -0.1297 +/- 0.2, respectively (P = 0.0004). The pancreas-spleen SI ratio (PSSI) in each group was 0.423 +/- 0.25 and 0.288 +/- 0.32, respectively (P = 0.014). Using quantitative analysis, the SI ratios were 1.27 and 0.66 in each group (P = 0.013). Conclusions: When analyzing the results of POPF in 43 patients who underwent PD, PLSI, PSSI and qualitative analysis, fistula group differed significantly from no fistula group. Using these results, it will be helpful for us to predict the occurrence of POPF pre-operatively using MRI in PD patients. C1 [Kim, Zisun; Kim, Min Joo; Choi, Dongho; Hur, Kyung Yul; Kim, Jae Joon; Lee, Min Hyuk; Moon, Chul] Soonchunhyang Univ, Coll Med, Dept Surg, Seoul 140743, South Korea. [Kim, Jung Hoon] Soonchunhyang Univ, Coll Med, Dept Radiol, Seoul 140743, South Korea. [Jin, So Young] Soonchunhyang Univ, Coll Med, Dept Pathol, Seoul 140743, South Korea. [Kim, Yong Bae] Soonchunhyang Univ, Coll Med, Dept Prevent Med, Cheonan, South Korea. [Seo, Daekwan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Choi, D (reprint author), Soonchunhyang Univ, Coll Med, Dept Surg, Seoul 140743, South Korea. EM dhchoi@hosp.sch.ac.kr NR 38 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1365-182X J9 HPB JI HPB PD MAY PY 2009 VL 11 IS 3 BP 215 EP 221 DI 10.1111/j.1477-2574.2009.00011.x PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA V15PO UT WOS:000207814100005 PM 19590650 ER PT J AU Wu, T Long, XY Zang, YF Wang, L Hallett, M Li, KC Chan, P AF Wu, Tao Long, Xiangyu Zang, Yufeng Wang, Liang Hallett, Mark Li, Kuncheng Chan, Piu TI Regional Homogeneity Changes in Patients With Parkinson's Disease SO HUMAN BRAIN MAPPING LA English DT Article DE Parkinson's disease; regional homogeneity; resting state; striatal-thalamo-cortical loops; brain activity ID SUPPLEMENTARY MOTOR AREA; CEREBRAL-BLOOD-FLOW; SUBTHALAMIC NUCLEUS STIMULATION; EXTERNALLY TRIGGERED MOVEMENTS; POSITRON EMISSION TOMOGRAPHY; STATE FUNCTIONAL MRI; RESTING-STATE; BASAL GANGLIA; PREFRONTAL CORTEX; PREMOTOR CORTEX AB Resting state brain activity in Parkinson's disease (PD) can give clues to the pathophysiology of the disorder, and might be helpful in diagnosis, but it has never been explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate PD-related modulations of neural activity in the resting state. FMRIs were acquired in 22 patients with PD at both before and after levodopa administration, as well as in 22 age- and sex-matched normal controls. In the PD group compared with the healthy controls, we found ReHo decreased in extensive brain regions, including the putamen, thalamus, and supplementary motor area; and increased in some other areas, including the cerebellum, primary sensorimotor cortex, and premotor area. The ReHo off medication was negatively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) in the putamen and some other regions, and was positively correlated with the UPDRS in the cerebellum. Administration of levodopa relatively normalized ReHo. Our findings demonstrate that neural activity in the resting state is changed in patients with PD. This change is secondary to dopamine deficiency, and related to the severity of the disease. The different neuronal activity at the baseline state should be considered in explaining fMRI findings obtained during tasks. Hum Brain Mapp 30:1502-1510, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Wu, Tao; Chan, Piu] Capital Med Univ, Dept Neurol, Beijing Inst Geriatr,Minist Educ, Xuanwu Hosp,Key Lab Neurodegenerate Disorder, Beijing 100053, Peoples R China. [Long, Xiangyu; Zang, Yufeng] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Wang, Liang; Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Chan, P (reprint author), Capital Med Univ, Dept Neurol, Beijing Inst Geriatr,Minist Educ, Xuanwu Hosp,Key Lab Neurodegenerate Disorder, 45 Changchun St, Beijing 100053, Peoples R China. EM pbchan@bjsap.org RI Wang, Liang/E-8652-2011; ZANG, Yu-Feng/J-1558-2012 OI ZANG, Yu-Feng/0000-0003-1833-8010 FU National Science Foundation of China [30570530] FX This work was supported by the National Science Foundation of China, Grant No. 30570530. NR 64 TC 184 Z9 205 U1 3 U2 27 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2009 VL 30 IS 5 BP 1502 EP 1510 DI 10.1002/hbm.20622 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440VK UT WOS:000265727600009 PM 18649351 ER PT J AU Rota, G Sitaram, R Veit, R Erb, M Weiskopf, N Dogil, G Birbaumer, N AF Rota, Giuseppina Sitaram, Ranganatha Veit, Ralf Erb, Michael Weiskopf, Nikolaus Dogil, Grzegorz Birbaumer, Niels TI Self-Regulation of Regional Cortical Activity Using Real-Time fMRI: The Right Inferior Frontal Gyrus and Linguistic Processing SO HUMAN BRAIN MAPPING LA English DT Article DE operant conditioning; self-regulation; real-time functional magnetic resonance imaging; right inferior frontal gyrus; prosody ID RESONANCE-IMAGING FMRI; EMOTIONAL PROSODY; RIGHT-HEMISPHERE; FUNCTIONAL MRI; BRAIN; LANGUAGE; NEUROFEEDBACK; SCHIZOPHRENIA; RECOVERY; APHASIA AB Neurofeedback of functional magnetic resonance imaging (fMRI) can be used to acquire selective control over activation in circumscribed brain areas, potentially inducing behavioral changes, depending on the functional role of the targeted cortical sites. In the present study, we used fMRI-neurofeedback to train subjects to enhance regional activation in the right inferior frontal gyrus (IFG) to influence speech processing and to modulate language-related performance. Seven subjects underwent real-time fMRI-neurofeedback training and succeeded in achieving voluntary regulation of their right Brodmann's area (BA) 45. To examine short-term behavioral impact, two linguistic tasks were carried out immediately before and after the training. A significant improvement of accuracy was observed for the identification of emotional prosodic intonations but not for syntactic processing. This evidence supports a role for the right IFG in the processing of emotional information and evaluation of affective salience. The present study confirms the efficacy of fMRI-biofeedback for noninvasive self-regulation of circumscribed brain activity. Hum Brain Mapp 30:1605-1614, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Rota, Giuseppina; Dogil, Grzegorz] Univ Stuttgart, Inst Nat Language Proc, D-70174 Stuttgart, Germany. [Rota, Giuseppina; Sitaram, Ranganatha; Veit, Ralf; Weiskopf, Nikolaus; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. [Veit, Ralf] Max Planck Inst Biol Cybernet, Tubingen, Germany. [Erb, Michael] Univ Tubingen, Dept Neuroradiol, Sect Expt MR, CNS, D-7400 Tubingen, Germany. [Weiskopf, Nikolaus] UCL, Inst Neurol, Wellcome Trust Ctr Neuroimaging, London WC1E 6BT, England. [Birbaumer, Niels] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Rota, G (reprint author), Univ Stuttgart, Inst Nat Language Proc, Azenbergstr 12, D-70174 Stuttgart, Germany. EM giuseppina.rota@uni-tuebingen.de RI Frank, David/E-8213-2012; Weiskopf, Nikolaus/B-9357-2008; Veit, Ralf/F-8907-2012; OI Weiskopf, Nikolaus/0000-0001-5239-1881; Veit, Ralf/0000-0001-9860-642X; Erb, Michael/0000-0002-9311-4693; Sitaram, Ranganatha/0000-0002-8577-8035 FU Graduiertenkolleg "Sprachliche Reprisentationen und ihre Interpretation" (University of Stuttgart); Deutsche Forschungsgemeinschaft (DFG), Germany; National Institutes of Health (NIH, NINDS), USA FX Graduiertenkolleg "Sprachliche Reprisentationen und ihre Interpretation" (University of Stuttgart); Deutsche Forschungsgemeinschaft (DFG), Germany; and National Institutes of Health (NIH, NINDS), USA. NR 61 TC 111 Z9 115 U1 0 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2009 VL 30 IS 5 BP 1605 EP 1614 DI 10.1002/hbm.20621 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440VK UT WOS:000265727600017 PM 18661503 ER PT J AU Nahab, FB Hattori, N Saad, ZS Hallett, M AF Nahab, Fatta B. Hattori, Noriaki Saad, Ziad S. Hallett, Mark TI Contagious Yawning and the Frontal Lobe: An fMRI Study SO HUMAN BRAIN MAPPING LA English DT Article DE contagion; fMRI; motor program; urge; ventromedial prefrontal cortex; yawning ID VENTROMEDIAL PREFRONTAL CORTEX; DECISION-MAKING; HUMAN BRAIN; EMPATHY; IMITATION; MIND; VISUALIZATION; ACTIVATION; SOFTWARE; JUDGMENT AB We conducted a slow event-related fMRI experiment with naive subjects' passively viewing yawn and various other control videos along with correlative behavioral testing. Specifically associated with the viewing of the contagious yawn was an area of activation in the ventromedial prefrontal cortex. These findings suggest a role for the prefrontal cortex in the processing of contagious yawning, while demonstrating a unique automaticity in the processing of contagious motor programs which take place independently of mirror neuron networks. Hum Brain Mapp 30:1744-1751, 2009. (C) 2008 Wiley-Liss, Inc. C1 [Nahab, Fatta B.; Hattori, Noriaki; Saad, Ziad S.; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD USA. RP Nahab, FB (reprint author), Univ Miami, Miller Sch Med, 1120 NW 14th St,Suite 1347, Miami, FL 33136 USA. EM nahabf@ninds.nih.gov FU Intramural Division of the National Institute of Neurological Disorders and Stroke, National Institutes of Health FX Contract grant sponsor: Intramural Division of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 43 TC 28 Z9 28 U1 6 U2 21 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2009 VL 30 IS 5 BP 1744 EP 1751 DI 10.1002/hbm.20638 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 440VK UT WOS:000265727600028 PM 18937281 ER PT J AU Grinshpun, A Condiotti, R Zeig, E Pe'er, M Waddington, SN Chou, JY Galun, E AF Grinshpun, A. Condiotti, R. Zeig, E. Pe'er, M. Waddington, S. N. Chou, J. Y. Galun, E. TI Successful Neonatal Gene Therapy of Glycogen Storage Disease Type Ia Using a Feline Immunodeficiency Virus-Based Vector SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 6th Annual Conference of the Israeli-Society-of-Gene-and-Cell-Therapy CY MAY 04, 2009 CL Ben Gurion Univ, Beer Sheva, ISRAEL SP Israel Soc Gene & Cell Therapy HO Ben Gurion Univ C1 [Grinshpun, A.; Condiotti, R.; Zeig, E.; Pe'er, M.; Galun, E.] Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, IL-91120 Jerusalem, Israel. [Waddington, S. N.] Univ London Imperial Coll Sci Technol & Med, Gene Therapy Res Grp, London SW7 2AY, England. [Chou, J. Y.] NICHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. EM albert.grinshpun@mail.huji.ac.il NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2009 VL 20 IS 5 BP 537 EP 538 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 445DU UT WOS:000266030700029 ER PT J AU Roessler, E Ma, Y Ouspenskaia, MV Lacbawan, F Bendavid, C Dubourg, C Beachy, PA Muenke, M AF Roessler, Erich Ma, Yong Ouspenskaia, Maia V. Lacbawan, Felicitas Bendavid, Claude Dubourg, Christele Beachy, Philip A. Muenke, Maximilian TI Truncating loss-of-function mutations of DISP1 contribute to holoprosencephaly-like microform features in humans SO HUMAN GENETICS LA English DT Article ID SONIC-HEDGEHOG GENE; SPECTRUM; EMBRYO; CELLS AB Defective function of the Sonic Hedgehog (SHH) signaling pathway is the most frequent alteration underlying holoprosencephaly (HPE) or its various clinical microforms. We performed an extensive mutational analysis of the entire human DISP1 gene, required for secretion of all hedgehog ligand(s) and which maps to the HPE 10 locus of human chromosome 1q41, as a HPE candidate gene. Here, we describe two independent families with truncating mutations in human DISP1 that resemble the cardinal craniofacial and neuro-developmental features of a recently described microdeletion syndrome that includes this gene; therefore, we suggest that DISP1 function contributes substantially to both of these signs in humans. While these clinical features are consistent with common HPE microforms, especially those linked to defective signaling by Sonic Hedgehog, we have insufficient evidence so far that functionally abnormal DISP1 alleles will commonly contribute to the more severe features of typical HPE. C1 [Roessler, Erich; Ouspenskaia, Maia V.; Lacbawan, Felicitas; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Bendavid, Claude; Dubourg, Christele] CHU Pontchaillou, Genet Mol Lab, IFR 140, Rennes, France. [Bendavid, Claude; Dubourg, Christele] Univ Rennes 1, IFR 140, Rennes, France. [Ma, Yong; Beachy, Philip A.] Johns Hopkins Univ, Baltimore, MD USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov FU Division of Intramural Research; National Human Genome Research Institute; NIH; research grants FX We thank the families who participated in these studies and for their ongoing support. This work was supported, in part, by the Division of Intramural Research, the National Human Genome Research Institute, NIH, and by research grants to P. A. B. NR 23 TC 30 Z9 31 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 2009 VL 125 IS 4 BP 393 EP 400 DI 10.1007/s00439-009-0628-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 435ZX UT WOS:000265383500004 PM 19184110 ER PT J AU Tran, DQ Shevach, EM AF Tran, Dat Q. Shevach, Ethan M. TI Therapeutic potential of FOXP3(+) regulatory T cells and their interactions with dendritic cells SO HUMAN IMMUNOLOGY LA English DT Article DE FOXP3; Tregs; Tolerance; Autoimmunity; Dendritic cells; LRRC32; GARP; TGFbeta; Latency associated peptide ID VERSUS-HOST-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ANTIGEN-PRESENTING CELLS; TGF-BETA; CUTTING EDGE; SUPPRESSOR FUNCTION; IN-VITRO; COSTIMULATORY MOLECULES; PERIPHERAL-BLOOD; APLASTIC-ANEMIA AB FOXP3(+) regulatory T cells, a unique subset of T cells, are critical for orchestrating an immune response and preventing Self-reactivity. With) the increasing prevalence and unsatisfactory treatment of autoimmunity, allergic diseases, cancer and chronic infections, much attention has been focused on understanding their mechanisms of action in order to manipulate their function. One goal is to develop drugs or biologics that can enhance or abrogate their functions. Another approach is to utilize Tregs in adoptive cell-based therapy to treat autoimmune diseases or transplant-related complications. This review will focus on their therapeutic potential and mechanisms of action, particularly their interaction with dendritic cells. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. C1 [Tran, Dat Q.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Tran, DQ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM dtran@niaid.nih.gov; eshevach@niaid.nih.gov NR 81 TC 35 Z9 39 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAY PY 2009 VL 70 IS 5 BP 294 EP 299 DI 10.1016/j.humimm.2009.02.007 PG 6 WC Immunology SC Immunology GA 441YM UT WOS:000265806500004 PM 19236900 ER PT J AU Udler, MS Meyer, KB Pooley, KA Karlins, E Struewing, JP Zhang, J Doody, DR MacArthur, S Tyrer, J Pharoah, PD Luben, R Bernstein, L Kolonel, LN Henderson, BE Le Marchand, L Ursin, G Press, MF Brennan, P Sangrajrang, S Gaborieau, V Odefrey, F Shen, CY Wu, PE Wang, HC Kang, D Yoo, KY Noh, DY Ahn, SH Ponder, BAJ Haiman, CA Malone, KE Dunning, AM Ostrander, EA Easton, DF AF Udler, Miriam S. Meyer, Kerstin B. Pooley, Karen A. Karlins, Eric Struewing, Jeffery P. Zhang, Jinghui Doody, David R. MacArthur, Stewart Tyrer, Jonathan Pharoah, Paul D. Luben, Robert Bernstein, Leslie Kolonel, Laurence N. Henderson, Brian E. Le Marchand, Loic Ursin, Giske Press, Michael F. Brennan, Paul Sangrajrang, Suleeporn Gaborieau, Valerie Odefrey, Fabrice Shen, Chen-Yang Wu, Pei-Ei Wang, Hui-Chun Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Ponder, Bruce A. J. Haiman, Christopher A. Malone, Kathleen E. Dunning, Alison M. Ostrander, Elaine A. Easton, Douglas F. CA SEARCH Collaborators TI FGFR2 variants and breast cancer risk: fine-scale mapping using African American studies and analysis of chromatin conformation SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM PATTERNS; GROWTH-FACTOR RECEPTOR-2; MULTIETHNIC COHORT; LOS-ANGELES; WOMEN; SUSCEPTIBILITY; POPULATIONS; GENES; POLYMORPHISM AB Genome-wide association studies have identified FGFR2 as a breast cancer (BC) susceptibility gene in populations of European and Asian descent, but a causative variant has not yet been conclusively identified. We hypothesized that the weaker linkage disequilibrium across this associated region in populations of African ancestry might help refine the set of candidate-causal single nucleotide polymorphisms (SNPs) previously identified by our group. Eight candidate-causal SNPs were evaluated in 1253 African American invasive BC cases and 1245 controls. A significant association with BC risk was found with SNP rs2981578 (unadjusted per-allele odds ratio = 1.20, 95% confidence interval 1.03-1.41, P(trend) = 0.02), with the odds ratio estimate similar to that reported in European and Asian subjects. To extend the fine-mapping, genotype data from the African American studies were analyzed jointly with data from European (n = 7196 cases, 7275 controls) and Asian (n = 3901 cases, 3205 controls) studies. In the combined analysis, SNP rs2981578 was the most strongly associated. Five other SNPs were too strongly correlated to be excluded at a likelihood ratio of < 1/100 relative to rs2981578. Analysis of DNase I hypersensitive sites indicated that only two of these map to highly accessible chromatin, one of which, SNP rs2981578, has previously been implicated in up-regulating FGFR2 expression. Our results demonstrate that the association of SNPs in FGFR2 with BC risk extends to women of African American ethnicity, and illustrate the utility of combining association analysis in datasets of diverse ethnic groups with functional experiments to identify disease susceptibility variants. C1 [Udler, Miriam S.; Pooley, Karen A.; Pharoah, Paul D.; Luben, Robert; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Tyrer, Jonathan; Pharoah, Paul D.; Ponder, Bruce A. J.; Dunning, Alison M.; SEARCH Collaborators] Univ Cambridge, Dept Oncol, Cambridge, England. [Udler, Miriam S.; Karlins, Eric; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Meyer, Kerstin B.; MacArthur, Stewart; Ponder, Bruce A. J.] Li Ka Shing Ctr, CRUK Cambridge Res Inst, Cambridge CB2 0RE, England. [Struewing, Jeffery P.; Zhang, Jinghui] US Natl Canc Inst, Lab Populat Genet, Bethesda, MD USA. [Doody, David R.; Malone, Kathleen E.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. [Henderson, Brian E.; Le Marchand, Loic; Ursin, Giske; Haiman, Christopher A.] USC, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Press, Michael F.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Brennan, Paul; Gaborieau, Valerie; Odefrey, Fabrice] Int Agcy Res Canc, F-69372 Lyon, France. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand. [Shen, Chen-Yang; Wu, Pei-Ei; Wang, Hui-Chun] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Ahn, Sei-Hyun] Natl Canc Ctr, Goyang, South Korea. RP Easton, DF (reprint author), Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England. EM douglas.easton@srl.cam.ac.uk RI Wang, Hui-Chun/C-5680-2009; Noh, Dong-Young/G-5531-2011; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Struewing, Jeffery/I-7502-2013; OI Struewing, Jeffery/0000-0002-4848-3334; Luben, Robert/0000-0002-5088-6343; Dunning, Alison Margaret/0000-0001-6651-7166; Ostrander, Elaine/0000-0001-6075-9738 FU Cancer Research UK; NIH-Oxford/Cambridge PhD program; US National Cancer Institute [CA 54281, CA 63464]; National Cancer Institute, through contracts with Emory University [N01 HD3-3168]; Fred Hutchinson Cancer Research Center [N01 HD2-3166]; Karmanos Cancer Institute at Wayne State University [N01 HD3-3174]; University of Pennsylvania [N01 HD3-3176]; University of Southern California [N01 HD3-3175]; Centers for Disease Control and Prevention [Y01 HD 7022]; SEER [N01-PC-67006, N01-CN-65064, N01-CN-67010, N01-CN-0532]; Hutchison Whampoa Limited FX The genotyping and analysis of this study, and the conduct of the SEARCH study, was funded by Cancer Research UK. DFE is a Principal Research Fellow of CR- UK and PDPP is a CR- UK Senior Clinical Research Fellow. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute and National Human Genome Research Institute, US Department of Health and Human Services. M. U. is supported by the NIH-Oxford/Cambridge PhD program. The Multiethnic Cohort Study was supported by the US National Cancer Institute [ CA 54281, CA 63464]. The CARE study was supported by the National Institute of Child Health and Human Development, with additional support from the National Cancer Institute, through contracts with Emory University [N01 HD3-3168], Fred Hutchinson Cancer Research Center [ N01 HD2-3166], Karmanos Cancer Institute at Wayne State University [ N01 HD3-3174], University of Pennsylvania [ N01 HD3-3176], University of Southern California [ N01 HD3-3175], and through an intra-agency agreement with the Centers for Disease Control and Prevention [Y01 HD 7022]. General support through SEER contracts [N01-PC-67006 ( Atlanta), N01-CN-65064 ( Detroit), N01-CN-67010 ( Los Angeles), and N01-CN-0532 ( Seattle)] are also acknowledged. BAJP is Li Ka Shing Professor of Oncology and we acknowledge Hutchison Whampoa Limited. NR 46 TC 81 Z9 82 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2009 VL 18 IS 9 BP 1692 EP 1703 DI 10.1093/hmg/ddp078 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 431WS UT WOS:000265096100015 PM 19223389 ER PT J AU Rossetti, R Di Pasquale, E Marozzi, A Bione, S Toniolo, D Grammatico, P Nelson, LM Beck-Peccoz, P Persani, L AF Rossetti, Raffaella Di Pasquale, Elisa Marozzi, Anna Bione, Silvia Toniolo, Daniela Grammatico, Paola Nelson, Lawrence M. Beck-Peccoz, Paolo Persani, Luca TI BMP15 Mutations Associated With Primary Ovarian Insufficiency Cause a Defective Production of Bioactive Protein SO HUMAN MUTATION LA English DT Article DE primary ovarian insufficiency; POI; BMP15; X chromosome; female fertility; premature ovarian failure; ovary; folliculogenesis ID BONE MORPHOGENETIC PROTEIN-15; INCREASED OVULATION RATE; TURNER-SYNDROME; XP DELETIONS; FRAGILE-X; 15 GENE; FAILURE; OOCYTE; SHEEP; IDENTIFICATION C1 [Rossetti, Raffaella; Di Pasquale, Elisa; Beck-Peccoz, Paolo; Persani, Luca] Univ Milan, Dept Med Sci, IRCCS, Ist Auxol Italiano,CIRMAR, I-20095 Cusano Milanino, MI, Italy. [Marozzi, Anna] Univ Milan, Dept Biol & Genet Med Sci, I-20095 Cusano Milanino, MI, Italy. [Rossetti, Raffaella; Di Pasquale, Elisa; Persani, Luca] IRCCS, Ist Auxol Italiano, Lab Expt Endocrinol, Milan, Italy. [Bione, Silvia] CNR, Inst Mol Genet, I-27100 Pavia, Italy. [Toniolo, Daniela] Ist Sci San Raffaele, Dept Biotechnol Res DIBIT, I-20132 Milan, Italy. [Grammatico, Paola] Univ Roma La Sapienza, San Camillo Forlanini Hosp, Dept Med Genet & Expt Med, Rome, Italy. [Nelson, Lawrence M.] NICHHD, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Beck-Peccoz, Paolo] Fdn Osped Maggiore Policlin IRCCS, Endocrinol & Diabetol Unit, Milan, Italy. RP Persani, L (reprint author), Univ Milan, Dept Med Sci, IRCCS, Ist Auxol Italiano,CIRMAR, Via Zucchi 18, I-20095 Cusano Milanino, MI, Italy. EM luca.persani@unimi.it RI Rossetti, Raffaella/B-4972-2013; OI Rossetti, Raffaella/0000-0001-9112-6175; Bione, Silvia/0000-0002-3924-4606; Persani, Luca/0000-0003-2068-9581 FU Cariplo Foundation [2005.1055/104878]; Istituto Auxologico Italiano [05C501]; Telethon [GGP05029] FX We are grateful to Dr. A.H. Brivanlou (Laboratory of Vertebrate Molecular Embryology, Rockfeller University, New York, NY) for providing the pCS2++ and the BRE-luciferase constructs and to Dr. CE van der Minne (Leiden University Medical Center, Leiden, The Netherlands) for providing the COV434 granulosa cells. This work was supported in part by grants from the Cariplo Foundation (2005.1055/104878 to L.P.), the Ricerca Corrente Funds of the Istituto Auxologico Italiano (05C501 to L.P.), and Telethon (GGP05029 to A.M., S.B., and D.T.). L.M.N. is a commissioned officer in the United States Public Health Service. NR 41 TC 57 Z9 63 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2009 VL 30 IS 5 BP 804 EP 810 DI 10.1002/humu.20961 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 441XN UT WOS:000265803900012 PM 19263482 ER PT J AU Levine, RJ Lindheimer, MD AF Levine, Richard J. Lindheimer, Marshall D. TI First-Trimester Prediction of Early Preeclampsia A Possibility at Last! SO HYPERTENSION LA English DT Editorial Material C1 [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Lindheimer, Marshall D.] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. [Lindheimer, Marshall D.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Levine, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov; mlindhei@medicine.bsd.uchicago.edu FU Intramural NIH HHS [NIH0010043600]; PHS HHS [NIH0010043600] NR 6 TC 20 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2009 VL 53 IS 5 BP 747 EP 748 DI 10.1161/HYPERTENSIONAHA.109.129379 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436XW UT WOS:000265450400002 PM 19273735 ER PT J AU Bonner, JC Card, JW Zeldin, DC AF Bonner, James C. Card, Jeffrey W. Zeldin, Darryl C. TI Nanoparticle-Mediated Drug Delivery and Pulmonary Hypertension SO HYPERTENSION LA English DT Editorial Material ID NF-KAPPA-B; CARBON NANOTUBES C1 [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Card, Jeffrey W.] Cantox Hlth Sci Int, Mississauga, ON, Canada. [Bonner, James C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS [Z01 ES025043-08]; NIEHS NIH HHS [Z01 ES025041] NR 10 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2009 VL 53 IS 5 BP 751 EP 753 DI 10.1161/HYPERTENSIONAHA.108.122846 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436XW UT WOS:000265450400004 PM 19307468 ER PT J AU Brinkley, TE Nicklas, BJ Kanaya, AM Satterfield, S Lakatta, EG Simonsick, EM Sutton-Tyrrell, K Kritchevsky, SB AF Brinkley, Tina E. Nicklas, Barbara J. Kanaya, Alka M. Satterfield, Suzanne Lakatta, Edward G. Simonsick, Eleanor M. Sutton-Tyrrell, Kim Kritchevsky, Stephen B. CA Hlth Aging Body Composition Study TI Plasma Oxidized Low-Density Lipoprotein Levels and Arterial Stiffness in Older Adults The Health, Aging, and Body Composition Study SO HYPERTENSION LA English DT Article DE aging; epidemiology; aortic stiffness; pulse wave velocity; oxidative stress ID CORONARY-HEART-DISEASE; PULSE-WAVE VELOCITY; ISOLATED SYSTOLIC HYPERTENSION; SMOOTH-MUSCLE CELLS; AORTIC STIFFNESS; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; INDEPENDENT PREDICTOR; SCAVENGER RECEPTORS; MAJOR SHAREHOLDERS AB Arterial stiffness is a prominent feature of vascular aging and is strongly related to cardiovascular disease. Oxidized low-density lipoprotein (ox-LDL), a key player in the pathogenesis of atherosclerosis, may also play a role in arterial stiffening, but this relationship has not been well studied. Thus, we examined the cross-sectional association between ox-LDL and aortic pulse wave velocity (aPWV), a marker of arterial stiffness, in community-dwelling older adults. Plasma ox-LDL levels and aPWV were measured in 2295 participants (mean age: 74 years; 52% female; 40% black) from the Health, Aging, and Body Composition Study. Mean aPWV significantly increased across tertiles of ox-LDL (tertile 1: 869 +/- 376 cm/s; tertile 2: 901 +/- 394 cm/s; tertile 3: 938 +/- 415 cm/s; P=0.002). In multivariate analyses, ox-LDL remained associated with aPWV after adjustment for demographics and traditional cardiovascular disease risk factors (P=0.008). After further adjustment for hemoglobin A1c, abdominal visceral fat, antihypertensive and antilipemic medications, and C-reactive protein, the association with ox-LDL was attenuated but remained significant (P=0.01). Results were similar when ox-LDL was expressed in absolute (milligrams per deciliter) or relative amounts (percentage of low-density lipoprotein). Moreover, individuals in the highest ox-LDL tertile were 30% to 55% more likely to have high arterial stiffness, defined as aPWV >75th percentile (P <= 0.02). In conclusion, we found that, among elderly persons, elevated plasma ox-LDL levels were associated with higher arterial stiffness, independent of cardiovascular disease risk factors. These data suggest that ox-LDL may be related to the pathogenesis of arterial stiffness. (Hypertension. 2009; 53: 846-852.) C1 [Brinkley, Tina E.] Wake Forest Univ, Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med,Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Kanaya, Alka M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Lakatta, Edward G.; Simonsick, Eleanor M.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Sutton-Tyrrell, Kim] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. RP Brinkley, TE (reprint author), Wake Forest Univ, Sch Med, Sect Gerontol & Geriatr Med, Dept Internal Med,Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM tbrinkle@wfubmc.edu OI Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institutes of Health, National Institute on Aging [N01-AG-6 to 2101, N01-AG6-2103, N01-AG-6-2106, R01-AG-027529-01A1S1] FX This research was supported by grants N01-AG-6 to 2101, N01-AG6-2103, N01-AG-6-2106, and R01-AG-027529-01A1S1. This research was also supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 48 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 2009 VL 53 IS 5 BP 846 EP 852 DI 10.1161/HYPERTENSIONAHA.108.127043 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436XW UT WOS:000265450400018 PM 19332658 ER PT J AU Wang, E Monaco, A Monsurro, V Sabatino, M Pos, Z Uccellini, L Wang, J Worschech, A Stroncek, DF Marincola, FM AF Wang, Ena Monaco, Alessandro Monsurro, Vladia Sabatino, Marianna Pos, Zoltan Uccellini, Lorenzo Wang, Jeanne Worschech, Andrea Stroncek, David F. Marincola, Francesco M. TI Antitumor vaccines, immunotherapy and the immunological constant of rejection SO IDRUGS LA English DT Review DE Cancer vaccines; melanoma; rejection; tumor immunology ID IMMUNITY; MICROENVIRONMENT; MELANOMA; LESSONS; TUMOR AB Anticancer vaccines have not matched the clinical expectations projected from their ability to induce consistently systemic anticancer T-cell responses. Thus, a dichotomy is observed between the immunological and clinical endpoints of anticancer immunization. Anticancer vaccines have clearly demonstrated that highly specific T-cell responses can be induced that can recognize autologous cancer antigens in patients with cancer. This ability is an outstanding achievement of modern biotechnology, yielding one of the most specific types of potential anticancer reagents. However, systemic, vaccine-induced anticancer responses exemplify a broader immunological paradox: cytotoxic T-cells can coexist within the same organism with their target cells not only in the context of cancer, but also in the context of chronic infections, well-controlled allo-transplant reactions and autoimmunity. According to this view, anticancer immune responses are a facet of a tissue-specific autoimmune phenomenon specific for cancer tissue that may or may not result in the successful immune-destruction of target cells, depending on an assortment of genetic factors related to the background of the host or evolving phenotypes of a heterogeneous cancer environment. This feature article summarizes the current understanding of the mechanisms leading to tumor rejection in humans as well as in experimental models, in the context of the broader immunological phenomenon leading to tissue-specific destruction. Anticancer vaccines that may not induce clinically significant anticancer responses independently could function as a unique tool to enhance the specificity of the response of the host against cancer, provided that strategies are implemented to amplify the immune reaction initiated by vaccine-induced antibodies and/or T-cells. C1 [Wang, Ena; Monaco, Alessandro; Sabatino, Marianna; Pos, Zoltan; Uccellini, Lorenzo; Wang, Jeanne; Worschech, Andrea; Stroncek, David F.; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Monsurro, Vladia] Univ Verona, Sch Med, Dept Pathol, I-37134 Verona, Italy. [Worschech, Andrea] Genelux Corp, San Diego Sci Ctr, San Diego, CA 92109 USA. [Worschech, Andrea] Univ Wurzburg, Dept Biochem, Bioctr, D-97074 Wurzburg, Germany. RP Marincola, FM (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov RI Worschech, Andrea/I-3919-2012; Pos, Zoltan/C-3623-2014; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Pos, Zoltan/0000-0002-2574-7616; Monaco, Alessandro/0000-0002-9941-7003 FU Intramural NIH HHS [ZIA CL002118-04, Z99 CL999999] NR 10 TC 12 Z9 12 U1 0 U2 1 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1369-7056 J9 IDRUGS JI IDrugs PD MAY PY 2009 VL 12 IS 5 BP 297 EP 301 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 445PD UT WOS:000266061900011 PM 19431094 ER PT J AU White, RJ Peng, GCY Demir, SS AF White, Ronald J. Peng, Grace C. Y. Demir, Semahat S. TI Multiscale Modeling of Biomedical, Biological, and Behavioral Systems (Part 2) Understanding the Body from Atoms to Cells to Tissues to Organs to Populations SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Editorial Material C1 [Peng, Grace C. Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. [Peng, Grace C. Y.] Catholic Univ Amer, Washington, DC 20064 USA. [Peng, Grace C. Y.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [White, Ronald J.] NASA, Human Res Program, Washington, DC USA. [White, Ronald J.] Baylor Coll Med, Houston, TX 77030 USA. [White, Ronald J.] NASA Headquarters, Div Life Sci, Washington, DC USA. [White, Ronald J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [White, Ronald J.] Univ Louisiana Lafayette, Lafayette, LA USA. [Demir, Semahat S.] NASA, SLS 1, Washington, DC USA. [Demir, Semahat S.] NASA, IML 1, Washington, DC USA. [Demir, Semahat S.] NASA, US Component German Spacelab Miss D 2, Washington, DC USA. RP Peng, GCY (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, 6707 Democracy Blvd,Suite 200,MSC 5469, Bethesda, MD 20892 USA. EM penggr@mail.nih.gov NR 0 TC 4 Z9 4 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAY-JUN PY 2009 VL 28 IS 3 BP 8 EP 9 DI 10.1109/MEMB.2009.932490 PG 2 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 449BK UT WOS:000266305600004 PM 19457728 ER PT J AU Park, S Witten, JM Myers, KJ AF Park, Subok Witten, Joel M. Myers, Kyle J. TI Singular Vectors of a Linear Imaging System as Efficient Channels for the Bayesian Ideal Observer SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Bayesian ideal observer; efficient channels; image quality; linear imaging system AB The Bayesian ideal observer provides an absolute upper bound for diagnostic performance of an imaging system and hence should be used for the assessment of image quality whenever possible. However, computation of ideal-observer performance in clinical tasks is difficult since the probability density functions of the data required for this observer are often unknown in tasks involving realistic, complex backgrounds. Moreover, the high dimensionality of the integrals that need to be calculated for the observer makes the computation more difficult. The ideal observer constrained to a set of channels, which we call a channelized-ideal observer (CIO), can reduce the dimensionality of the problem. These channels are called efficient if the CIO can approximate ideal-observer performance. In this paper, we propose a method to choose efficient channels for the ideal observer based on a singular value decomposition of a linear imaging system. As a demonstration, we test our method on detection tasks using non-Gaussian lumpy backgrounds and signals of Gaussian and elliptical profiles. Our simulation results show that singular vectors associated with either the background or the signal are highly efficient for the ideal observer for detecting both types of signals. In addition, this CIO outperforms a channelized-Hotelling observer with the same channels. C1 [Park, Subok; Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. [Witten, Joel M.] Univ Maryland, Dept Math, College Pk, MD 20742 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, White Oak, MD 20993 USA. EM subok.park@fda.hhs.gov NR 11 TC 12 Z9 12 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAY PY 2009 VL 28 IS 5 BP 657 EP 668 DI 10.1109/TMI.2008.2008967 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 441DB UT WOS:000265748400003 PM 19272990 ER PT J AU Badano, A Kyprianou, IS Freed, M Jennings, RJ Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Freed, Melanie Jennings, Robert J. Sempau, Josep TI Effect of Oblique X-ray Incidence in Flat-Panel Computed Tomography of the Breast SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE Breast computed tomography (CT); Cesium Iodide; Monte Carlo simulation; phosphor blur; phosphor screen ID MONTE-CARLO-SIMULATION; ANISOTROPIC IMAGING PERFORMANCE; POINT-SPREAD FUNCTION; CODE PENELOPE; CT SCANNER; ELECTRON; TOMOSYNTHESIS; RESOLUTION; LEKSELL-GAMMA-KNIFE(R); COLLECTION AB We quantify the variation in resolution due to anisotropy caused by oblique X-ray incidence in indirect flat-panel detectors for computed tomography breast imaging systems. We consider a geometry and detector type utilized in breast computed tomography (CT) systems currently being developed. Our methods rely on MANTIS, a combined X-ray, electron, and optical Monte Carlo transport open source code. The physics models are the most accurate available in general-purpose Monte Carlo packages in the diagnostic energy range. We consider maximum-obliquity angles of 10 degrees and 13 degrees at the centers of the 30 and 40 cm detector edges, respectively, and 160 at the corner of the detector. Our results indicate that blur is asymmetric and that the resolution properties vary significantly with the angle (or location) of incidence. Our results suggest that the asymmetry can be as high as a factor of 2.6 between orthogonal directions. Anisotropy maps predicted by MANTIS provide an understanding of the effect that such variations have on the imaging system and allow more accurate modeling and optimization of breast CT systems. These maps of anisotropy across the detector could lead to improved reconstruction and help motivate physics-based strategies for computer detection of breast lesions. C1 [Badano, Aldo; Kyprianou, Iacovos S.; Freed, Melanie; Jennings, Robert J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Sempau, Josep] Biomat & Nanomed CIBER BBN, Spanish Networking Res Ctr Bioengn, Zaragoza 20018, Spain. RP Badano, A (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 38 TC 8 Z9 8 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD MAY PY 2009 VL 28 IS 5 BP 696 EP 702 DI 10.1109/TMI.2008.2010443 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 441DB UT WOS:000265748400007 PM 19272986 ER PT J AU Joshi, BH Puri, RK AF Joshi, Bharat H. Puri, Raj K. TI IL-13 receptor-alpha 2: a novel target for cancer therapy SO IMMUNOTHERAPY LA English DT Editorial Material ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; INTERLEUKIN (IL)-13 BINDING; CHIMERIC FUSION PROTEINS; CARCINOMA CELL-LINES; COMMON GAMMA-CHAIN; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; ALPHA-2 CHAIN; NECK-CANCER C1 [Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 2NN20, Bethesda, MD 20892 USA. EM bharat.joshi@fda.hhs.gov; raj.puri@fda.hhs.gov NR 79 TC 10 Z9 12 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY JI Immunotherapy PD MAY PY 2009 VL 1 IS 3 BP 321 EP 327 DI 10.2217/IMT.09.8 PG 7 WC Immunology SC Immunology GA 546RA UT WOS:000273826800001 PM 20635949 ER PT J AU Wang, E Albini, A Stroncek, DF Marincola, FM AF Wang, Ena Albini, Adriana Stroncek, David F. Marincola, Francesco M. TI New take on comparative immunology: relevance to immunotherapy SO IMMUNOTHERAPY LA English DT Review DE chronic infection; comparative immunology; tumor immunology; vaccine ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; TUMOR-INFILTRATING LYMPHOCYTES; PATIENTS RECEIVING IMMUNOTHERAPY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HUMAN INTERLEUKIN-8 RECEPTOR; BARR-VIRUS INFECTION; HUMAN BREAST-TUMORS; METASTATIC MELANOMA; TRANSLATIONAL MEDICINE; MUC1 IMMUNOTHERAPY AB It is becoming increasingly recognized that experimental animal models, while useful to address monothematic biological questions, bear unpredictable relevance to human disease. Several reasons have been proposed. However, the uncontrollable nature of human genetics and the heterogeneity of disease that can only be replicated with difficulty experimentally play a leading role. Comparative immunology is a term that generally refers to the analysis of shared or diverging facets of immunology among species; these comparisons are carried out according to the principle that evolutionarily conserved themes outline biologic functions universally relevant for survival. We propose that a similar strategy could be applied to searching for themes shared by distinct immune pathologies within our own species. Identification of common patterns may outline pathways necessary for a particular determinism to occur, such as tissue-specific rejection or tolerance. This approach is founded on the unproven but sensible presumption that nature does not require an infinite plethora of redundant mechanisms to reach its purposes. Thus, immune pathologies must follow, at least in part, common means that determine their onset and maintenance. Commonalities among diseases can, in turn, be segregated from disease-specific patterns uncovering essential mechanisms that may represent universal targets for immunotherapy. C1 [Wang, Ena; Stroncek, David F.; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Clin Ctr & Ctr Human Immunol, Bethesda, MD 20892 USA. [Albini, Adriana] IRCCS Multimedia, Milan, Italy. RP Marincola, FM (reprint author), NIH, IDIS, Dept Transfus Med, Clin Ctr & Ctr Human Immunol, R-1C711,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov FU Intramural NIH HHS [ZIA CL002118-04] NR 123 TC 5 Z9 5 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY JI Immunotherapy PD MAY PY 2009 VL 1 IS 3 BP 355 EP 366 DI 10.2217/IMT.09.10 PG 12 WC Immunology SC Immunology GA 546RA UT WOS:000273826800009 PM 20635956 ER PT J AU Cossarini, F Mican, JA Polis, M Rehm, CA O'Shea, A Poethke, C Maldarelli, F AF Cossarini, F. Mican, J. A. Polis, M. Rehm, C. A. O'Shea, A. Poethke, C. Maldarelli, F. TI LONG-TERM ANTIRETROVIRAL THERAPY IN HIV-1 INFECTED PATIENTS REDUCES CELLULAR IMMUNE ACTIVATION MARKERS TO LEVEL DETECTED IN UNINFECTED INDIVIDUALS SO INFECTION LA English DT Meeting Abstract C1 [Cossarini, F.; Poethke, C.; Maldarelli, F.] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. [Cossarini, F.] Ist Sci San Raffaele, Dept Infect Dis, I-20132 Milan, Italy. [Mican, J. A.; Rehm, C. A.; O'Shea, A.] NIAID, NIH, Bethesda, MD 20892 USA. [Polis, M.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD MAY PY 2009 VL 37 BP 82 EP 82 PG 1 WC Infectious Diseases SC Infectious Diseases GA 473YC UT WOS:000268247200128 ER PT J AU Mancini, N Canducci, F De Marco, D Clementi, N Sassi, M Shvela, K Bagnarelli, P Mascola, JR Clementi, M Burioni, R AF Mancini, N. Canducci, F. De Marco, D. Clementi, N. Sassi, M. Shvela, K. Bagnarelli, P. Mascola, J. R. Clementi, M. Burioni, R. TI ANTI-HIV-1 RESPONSE ELICITED IN RABBITS BY ANTI-IDIOTYPE MONOCLONAL ANTIBODIES MIMICKING THE CD4-BINDING SITE ON GP120 SO INFECTION LA English DT Meeting Abstract C1 [Mancini, N.; Canducci, F.; De Marco, D.; Clementi, N.; Sassi, M.; Clementi, M.; Burioni, R.] Univ Vita Salute San Raffaele, Ist Sci San Raffaele Diagnost & Ric San Raffaele, Lab Microbiol & Virol, Milan, Italy. [Shvela, K.; Mascola, J. R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Bagnarelli, P.] Univ Politecn Marche, Virol Lab, Ancona, Italy. RI Burioni, Roberto /F-2396-2012; Clementi, Massimo/F-6646-2013; Clementi, Nicola/G-8545-2014 OI Clementi, Nicola/0000-0002-1822-9861 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD MAY PY 2009 VL 37 BP 85 EP 85 PG 1 WC Infectious Diseases SC Infectious Diseases GA 473YC UT WOS:000268247200135 ER PT J AU Buonaguro, L Monac, A Tornesello, ML Lewis, GK Marincola, FM Buonaguro, FM AF Buonaguro, L. Monac, A. Tornesello, M. L. Lewis, G. K. Marincola, F. M. Buonaguro, F. M. TI MOLECULAR IMMUNE SIGNATURES OF HIV-1 VACCINES SO INFECTION LA English DT Meeting Abstract C1 [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fdn G Pascale, Lab Mol Biol & Viral Oncogenesis, Naples, Italy. [Buonaguro, L.; Tornesello, M. L.; Buonaguro, F. M.] Ist Nazl Tumori Fdn G Pascale, AIDS Reference Ctr, Naples, Italy. [Monac, A.; Marincola, F. M.] NIH, Dept Transfus Med, Ctr Clin, IDIS, Bethesda, MD 20892 USA. [Lewis, G. K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RI Tornesello, Maria Lina/A-1564-2009 OI Tornesello, Maria Lina/0000-0002-3523-3264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD MAY PY 2009 VL 37 BP 86 EP 86 PG 1 WC Infectious Diseases SC Infectious Diseases GA 473YC UT WOS:000268247200136 ER PT J AU Isokpehi, RD Chambwe, N Murray, JM Cohly, HHP Varadharajan, S Rajnarayanan, RV AF Isokpehi, Raphael D. Chambwe, N. Murray, J. M. Cohly, H. H. P. Varadharajan, S. Rajnarayanan, R. V. TI Information Superstructure for Protozoan Aquaporins SO INFECTION GENETICS AND EVOLUTION LA English DT Meeting Abstract C1 [Isokpehi, Raphael D.; Chambwe, N.; Murray, J. M.; Cohly, H. H. P.] Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. [Isokpehi, Raphael D.; Chambwe, N.; Murray, J. M.; Cohly, H. H. P.] Jackson State Univ, RCMI Ctr Environm Hlth, Jackson, MS 39217 USA. [Rajnarayanan, R. V.] Tougaloo Coll, Dept Chem, Jackson, MS USA. EM raphael.isokpehi@jsums.edu RI Chambwe, Nyasha/M-7796-2013 OI Chambwe, Nyasha/0000-0002-2812-0122 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD MAY PY 2009 VL 9 IS 3 BP 370 EP 370 PG 1 WC Infectious Diseases SC Infectious Diseases GA 446OE UT WOS:000266130100017 ER PT J AU Oviedo, MN Ribeiro, JMC Heyland, A VanEkeris, L Moroz, T Linser, PJ AF Oviedo, M. Neira Ribeiro, J. M. C. Heyland, A. VanEkeris, L. Moroz, T. Linser, P. J. TI The salivary transcriptome of Anopheles gambiae (Diptera: Culicidae) larvae: A microarray-based analysis SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE Anopheles gambiae; Salivary gland; Diptera; Gene expression; Salivary defensin; Transcriptome; Salivary lipocalin ID ADULT FEMALE MOSQUITO; FIBRINOGEN-LIKE DOMAIN; AMINO-ACID-SEQUENCES; ANTIMICROBIAL PEPTIDES; DROSOPHILA-MELANOGASTER; ANTIBACTERIAL ACTIVITY; PROTEINASE-INHIBITORS; GLAND TRANSCRIPTS; RHODNIUS-PROLIXUS; SERINE PROTEASES AB In spite of the many recent developments in the field of vector sialomics, the salivary glands of larval mosquitoes have been largely unexplored. We used whole-transcriptome microarray analysis to create a gene-expression profile of the salivary gland tissue of fourth-instar Anopheles gambiae larvae, and compare it to the gene-expression profile of a matching group of whole larvae. We identified a total of 221 probes with expression values that were (a) significantly enriched in the salivary glands, and (b) sufficiently annotated as to allow the prediction of the presence/absence of signal peptides in their corresponding gene products. Based on available annotation of the protein sequences associated with these probes, we propose that the main roles of larval salivary secretions include: (a) immune response, (b) mouthpart lubrication, (c) nutrient metabolism, and (d) xenobiotic detoxification. Other highlights of the study include the cloning of a transcript encoding a previously unknown salivary defensin (AgDef5), the confirmation of mucus secretion by the larval salivary glands, and the first report of salivary lipocalins in the Culicidae. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Oviedo, M. Neira; VanEkeris, L.; Moroz, T.; Linser, P. J.] Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL USA. [Ribeiro, J. M. C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [Heyland, A.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada. RP Oviedo, MN (reprint author), Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL USA. EM mneira@whitney.ufl.edu RI Neira Oviedo, Marco/C-5706-2009; OI Heyland, Andreas/0000-0002-7592-4473; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400, N01CO12400]; NIAID NIH HHS [R01 AI045098-10, R01 AI045098, R01-AI045098] NR 100 TC 16 Z9 19 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD MAY-JUN PY 2009 VL 39 IS 5-6 BP 382 EP 394 DI 10.1016/j.ibmb.2009.03.001 PG 13 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 464LA UT WOS:000267505200009 PM 19328852 ER PT J AU Huter, EN Stummvoll, GH DiPaolo, RJ Glass, DD Shevach, EM AF Huter, Eva N. Stummvoll, Georg H. DiPaolo, Richard J. Glass, Deborah D. Shevach, Ethan M. TI Pre-differentiated Th1 and Th17 effector T cells in autoimmune gastritis: Ag-specific regulatory T cells are more potent suppressors than polyclonal regulatory T cells SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE Autoimmune gastritis; T helper cells; IL17; Tolerance; Regulatory T cells ID PREVENT; DISEASE AB Naive antigen-specific CD4(+) T cells (TxA23) induce autoimmune gastritis when transferred into BALB/c nu/nu mice. Transfer of in vitro pre-differentiated Th1 or Th17 TxA23 effector T cells into BALB/c nu/nu recipients induces distinct histological patterns of disease. We have previously shown that co-transfer of polyclonal naturally occurring Treg (nTreg) suppressed development of Th1-, but not Th17-mediated disease. Therefore, we analysed the suppressive capacity of different types of Treg to suppress Th1- and Th17-mediated autoimmune gastritis. We compared nTreg with polyclonal TGF beta-induced WT Treg (iTreg) or TGF beta-induced antigen-specific TxA23 iTreg in co-transfer experiments with Th1 or Th17 TxA23 effector T cells. 6 weeks after transfer in vitro pre-differentiated TxA23 Th1 and Th17 effector cells induced destructive gastritis. Th1-mediated disease was prevented by co-transfer of nTreg and also antigen-specific iTreg, whereas WT iTreg did not show an effect. However, Th17-mediated disease was only suppressed by antigen-specific iTreg. Pre-activation of nTreg in vitro prior to transfer did not increase their suppressive activity in Th17-mediated gastritis. Thus, antigen-specific iTreg are potent suppressors of autoimmune gastritis induced by both, fully differentiated Th1 and Th17 effector cells. (C) Published by Elsevier B.V. C1 [Huter, Eva N.; Glass, Deborah D.; Shevach, Ethan M.] NIAID, NIH, Immunol Lab, Cellular Immunol Sect, Bethesda, MD 20892 USA. [Stummvoll, Georg H.] Med Univ Vienna, Dept Rheumatol, Vienna, Austria. [DiPaolo, Richard J.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. RP Shevach, EM (reprint author), NIAID, NIH, Immunol Lab, Cellular Immunol Sect, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov FU Intramural Research Program of the National Institutes of Health; National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 12 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAY PY 2009 VL 9 IS 5 BP 540 EP 545 DI 10.1016/j.intimp.2009.01.022 PG 6 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 440QW UT WOS:000265715800007 PM 19539565 ER PT J AU Hong, SH Briggs, J Newman, R Hoffman, K Mendoza, A LeRoith, D Helman, L Yakar, S Khanna, C AF Hong, Sung-Hyeok Briggs, Joseph Newman, Rachel Hoffman, Karen Mendoza, Arnulfo LeRoith, Derek Helman, Lee Yakar, Shoshana Khanna, Chand TI Murine osteosarcoma primary tumour growth and metastatic progression is maintained after marked suppression of serum insulin-like growth factor I SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE tumour microenvironment; insulin-like growth factor I; murine; osteosarcoma; pulmonary metastasis ID PEDIATRIC-ONCOLOGY-GROUP; HIGH-DOSE CHEMOTHERAPY; STUDY-GROUP PROTOCOLS; PROSTATE-CANCER RISK; RELAPSED OSTEOSARCOMA; IGF-I; RECEPTOR; CHILDREN; TRIAL; MICE AB The insulin-like growth factor I (IGF-I) signaling pathway has been shown to play an important role in several aspects of cancer biology, including metastasis. The aim of this study was to define the contribution of serum (endocrine) and local (tumour microenvironment) IGF-I on osteosarcoma tumour growth and metastasis, a cancer that is known to be dependent on the IGF-I axis. To test this hypothesis, we evaluated the primary tumour growth and metastatic progression of K7M2 murine osteosarcoma cells injected to a genetically engineered mouse [liver-specific IGF-I deficient (LID)] in which serum IGF-I levels are reduced by 75%, while maintaining expression of IGF-I in normal tissues. We first demonstrated that IGF-I in the tumour and the tumour-microenvironment were maintained in the LID mice. Within this designed model, there was no difference in primary tumour growth or in pulmonary metastasis in LID mice compared to control mice. Furthermore, there was no difference in the number or localization of single metastatic cells immediately after their arrival in the lungs of LID mice and control mice, as analysed by single cell video microscopy. Collectively, these data suggest that marked reduction in serum IGF-I is not sufficient to slow the progression of either primary or metastatic models of osteosarcoma. (C) 2008 Wiley-Liss, Inc. C1 [Hong, Sung-Hyeok; Briggs, Joseph; Newman, Rachel; Hoffman, Karen; Mendoza, Arnulfo; Helman, Lee; Khanna, Chand] NCI, NIH, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [LeRoith, Derek; Yakar, Shoshana] Mt Sinai Sch Med, Dept Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Khanna, C (reprint author), NCI, NIH, Pediat Oncol Branch, 37 Convent Dr,Room 2144, Rockville, MD 20892 USA. EM khannac@mail.nih.gov NR 36 TC 11 Z9 12 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2009 VL 124 IS 9 BP 2042 EP 2049 DI 10.1002/ijc.24169 PG 8 WC Oncology SC Oncology GA 425OS UT WOS:000264647600006 PM 19132750 ER PT J AU Sutcliffe, S Alderete, JF Till, C Goodman, PJ Hsing, AW Zenilman, JM De Marzo, AM Platz, EA AF Sutcliffe, Siobhan Alderete, John F. Till, Cathee Goodman, Phyllis J. Hsing, Ann W. Zenilman, Jonathan M. De Marzo, Angelo M. Platz, Elizabeth A. TI Trichomonosis and subsequent risk of prostate cancer in the Prostate Cancer Prevention Trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE trichomonosis; Trichomonas vaginalis; sexually; transmitted infection; prostate cancer; epidemiology ID VAGINAL EPITHELIAL-CELLS; IN-VITRO AB We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men (>= 55 years of age) with no evidence of prostate cancer. at enrollment (n = 18,8821). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end-of-study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end-of-study biopsy (it = 616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n = 616). Controls were frequency-matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti-T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 95% confidence interval (Cl): 0.6.3-1.09), and that for men with high seropositivity was 0.97 (95% Cl: 0.70-1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings and to further investigate this hypothesis from a variety of different approaches. (C) 2008 Wiley-Liss, Inc. C1 [Sutcliffe, Siobhan] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Sutcliffe, Siobhan] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Alderete, John F.] Washington State Univ, Sch Mol Biosci, Pullman, WA 99164 USA. [Till, Cathee; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hsing, Ann W.] NCI, NIH, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zenilman, Jonathan M.] Johns Hopkins Med Inst, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. [De Marzo, Angelo M.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [De Marzo, Angelo M.; Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Sutcliffe, S (reprint author), Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, 660 So Euclid Ave,Box 8109,Room 5026, St Louis, MO 63110 USA. EM sutcliffes@wudosis.wustl.edu OI Sutcliffe, Siobhan/0000-0002-4613-8107 FU NCI NIH HHS [P01 CA108964, P01 CA108964-04] NR 17 TC 36 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2009 VL 124 IS 9 BP 2082 EP 2087 DI 10.1002/ijc.24144 PG 6 WC Oncology SC Oncology GA 425OS UT WOS:000264647600011 PM 19117055 ER PT J AU Gierach, GL Chang, SC Brinton, LA Lacey, JV Hollenbeck, AR Schatzkin, A Leitzmann, MF AF Gierach, Gretchen L. Chang, Shih-Chen Brinton, Louise A. Lacey, James V., Jr. Hollenbeck, Albert R. Schatzkin, Arthur Leitzmann, Michael F. TI Physical activity, sedentary behavior, and endometrial cancer risk in the NIH-AARP Diet and Health Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE endometrial neoplasnis/epidemiology; exercise/physiology; recreation/physiology; health behavior; prospective studies ID LIFE-STYLE; POSTMENOPAUSAL WOMEN; NATIONAL-INSTITUTES; PROSPECTIVE COHORT; UNITED-STATES; MECHANISMS; HORMONES; OBESITY; OVERWEIGHT; SHANGHAI AB Consistent with a strong hormonal etiology, endometrial cancer is thought to be influenced by both obesity and physical activity. Although obesity has been consistently related to risk, associations with physical activity have been inconclusive. We examined relationships of activity patterns with endometrial cancer incidence in the NIH-AARP Diet and Health Stud), cohort, which included 109,621 women, ages 50-71, without cancer history, who in 19951996 completed a mailed baseline questionnaire capturing daily routine and vigorous (defined as any period of >= 20 min of activity at work or home causing increases in breathhng, heart rate, or sweating) physical activity. A second questionnaire, completed by 70,351 women, in 1996-1497 collected additional physical activity information. State cancer registry linkage identified 1,052 primary incident endometrial cancers from baseline through December 31, 2003. In multivariate proportional hazards models, vigorous activity was inversely associated with endometrial cancer in a dose-response manner (, p for trend = 0.02) (relative risk (RR) for >= 5 times/week vs. never/rarely = 0.77, 95% confidence interval (CI) 0.63-0.95), this association was more pronounced among overweight and obese women (body mass index >= 25; RR = 0.61, 95% CI: 0.47-4).79) than among lean women (body mass index <25; RR = 0.76, 95% CI: 0.52-1.10; p for interaction = 0.12). Although we observed no associations with light/moderate, daily routine or occupational physical activities, risk did increase with number of hours of daily sitting (p for trend = 0.02). Associations with vigorous activities, which may interact with body mass index, suggest directions for future research to clarify underlying biologic mechanisms. including those relating to hormonal alterations. (C) 2008 Wiley-Liss. Inc. C1 [Gierach, Gretchen L.; Brinton, Louise A.; Lacey, James V., Jr.] NCI, NIH, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Gierach, Gretchen L.] NCI, NIH, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Chang, Shih-Chen] AstraZeneca, Wilmington, DE USA. [Hollenbeck, Albert R.] AARP, Organizat & Tracking Res Dept, Washington, DC USA. [Schatzkin, Arthur; Leitzmann, Michael F.] NCI, NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Gierach, GL (reprint author), 6120 Execut Blvd Suite 550,Room 5010 MSC 7234, Rockville, MD 20852 USA. EM gierachg@mail.nih.gov RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU Intramural NIH HHS [Z01 CP010196-01] NR 45 TC 66 Z9 69 U1 0 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2009 VL 124 IS 9 BP 2139 EP 2147 DI 10.1002/ijc.24059 PG 9 WC Oncology SC Oncology GA 425OS UT WOS:000264647600018 PM 19123463 ER PT J AU Murphy, G Cross, AJ Sansbury, LS Bergen, A Laiyemo, AO Albert, PS Wang, ZQ Yu, BB Lehman, T Kalidindi, A Modali, R Schatzkin, A Lanza, E AF Murphy, Gwen Cross, Amanda J. Sansbury, Leah S. Bergen, Andrew Laiyemo, Adeyinka O. Albert, Paul S. Wang, Zhuoqiao Yu, Binbing Lehman, Teresa Kalidindi, Aravind Modali, Rama Schatzkin, Arthur Lanza, Elaine TI Dopamine D-2 receptor polymorphisms and adenoma recurrence in the Polyp Prevention Trial SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GENE; RISK; DRD2; SCHIZOPHRENIA; OBESITY; TRAITS; DESIGN AB Epidemiological evidence suggests that obesity may be causally associated with colorectal cancer. Dopamine and the dopaminergic reward pathway have been implicated in drug and alcohol addiction as well as obesity. Polymorphisms within the D2 dopamine receptor gene (DRD2) have been shown to be associated with colorectal cancer risk. We investigated the association between DRD2 genotype at these loci and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. Individuals with any, multiple (>= 2) or advanced adenoma recurrence after 4 years were compared to those without adenoma recurrence. Variation in intake of certain dietary components according to DRD2 genotype at 3 loci (rs1799732; rs6277; rs1800497) was also investigated. The DRD2 rs1799732 CT genotype was significantly associated with all adenoma recurrence (OR: 1.30; 95% CI: 1.01, 11.69). The rs1800497 TT genotype was also associated with a significantly increased risk of advanced adenoma recurrence (OR: 2.40; 95% CI: 1.11, 5.20). The rs1799732 CT and rs1800497 TT genotypes were significantly associated with adenoma recurrence in the Polyp Prevention Trial. Increased risk of adenoma recurrence as conferred by DRD2 genotypes may be related to difference in alcohol and fat intake across genotypes. Published 2008 Wiley-Liss, Inc. C1 [Murphy, Gwen] NCI, Infect & Immunoepidemiol Branch, Canc Prevent Fellowship Program, Off Prevent Oncol, Bethesda, MD 20892 USA. [Murphy, Gwen; Cross, Amanda J.; Sansbury, Leah S.; Bergen, Andrew; Schatzkin, Arthur; Lanza, Elaine] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sansbury, Leah S.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Laiyemo, Adeyinka O.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. [Wang, Zhuoqiao; Yu, Binbing] Informat Management Serv Inc, Rockville, MD USA. [Lehman, Teresa; Kalidindi, Aravind; Modali, Rama] BioServe Biotechnol Ltd, Beltsville, MD USA. RP Murphy, G (reprint author), NCI, Infect & Immunoepidemiol Branch, Canc Prevent Fellowship Program, Off Prevent Oncol, 6120 Execut Blvd,Rm 7067, Bethesda, MD 20892 USA. EM murphygw@mail.nih.gov RI Murphy, Gwen/G-7443-2015; OI Bergen, Andrew/0000-0002-1237-7644 FU Intramural Research Program; National Cancer Institute, NIH, Bethesda, MD; Ireland-Northern Ireland-National Cancer Institute Cancer Consortium; Health Research Board of Ireland FX Grain sponsor Intramural Research Program, National Cancer Institute, NIH, Bethesda, MD. Grant sponsor: Ireland-Northern Ireland-National Cancer Institute Cancer Consortium and the Health Research Board of Ireland. NR 23 TC 4 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2009 VL 124 IS 9 BP 2148 EP 2151 DI 10.1002/ijc.24079 PG 4 WC Oncology SC Oncology GA 425OS UT WOS:000264647600019 PM 19065655 ER PT J AU Rastmanesh, R Gluck, ME Shadman, Z AF Rastmanesh, Reza Gluck, Marci E. Shadman, Zhaleh TI Comparison of Body Dissatisfaction and Cosmetic Rhinoplasty with Levels of Veil Practicing in Islamic Women SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE body image; Islamic veil practicing; cosmetic surgery; depression; self-esteem ID BINGE-EATING DISORDER; PSYCHOMETRIC PROPERTIES; ADOLESCENT FEMALES; WEIGHT CONCERNS; MEDIA; IMAGE; SATISFACTION; IRAN; QUESTIONNAIRE; VALIDATION AB Objective: The relationship between Islamic veiling, body dissatisfaction, and desire for cosmetic rhinoplasty (CR) has not been studied. We therefore compared body dissatisfaction (BD), depression, self-esteem, and prevalence anti desire to have CR in 1,771 Iranian females. Method: A battery of questionnaires was administered and participants were categorized into three groups of Islamic veil practicing: voluntarily and ideologically (IVP), non-complete (NCIVP), and Inconsiderate (IIVP). Results: Despite a similar BMI, the IVP group scored significantly lower on BID, prevalence of dieting and exercising in order to be sexually appealing, and depression, higher on self-esteem, and had a lower desire for a CR than the two other groups. Prevalence of CR was significantly higher in the IIVP group than the other groups. Discussion: Women who practiced more strict Islamic veiling techniques had increased body satisfaction and self esteem, and decreased depression scores and desire for CR. Consistent with other studies, our findings show that observance of a strict religious practice has a protective effect on psychological health. (C) 2008 by Wiley Periodicals, Inc. C1 [Rastmanesh, Reza] SBMU, Fac Nutr, Dept Human Nutr, Tehran, Iran. [Gluck, Marci E.] NIDDK, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA. RP Rastmanesh, R (reprint author), SBMU, Fac Nutr, Dept Human Nutr, Farahzadi Blvd,POB 19395-4741, Tehran, Iran. EM r.rastmanesh@sbmu.ac.ir FU NIH, NIDDK FX This work was partially supported by the Intramural Research Program of the NIH, NIDDK. NR 39 TC 9 Z9 9 U1 5 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 2009 VL 42 IS 4 BP 339 EP 345 DI 10.1002/eat.20613 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 436NH UT WOS:000265420300007 PM 19115373 ER PT J AU Gage, JC Rodriguez, AC Schiffman, M Adadevoh, S Larraondo, MJA Chumworathayi, B Lejarza, SV Araya, LV Garcia, F Budihas, SR Long, R Katki, HA Herrero, R Burk, RD Jeronimo, J AF Gage, Julia C. Cecilia Rodriguez, Ana Schiffman, Mark Adadevoh, Sydney Alvarez Larraondo, Manuel J. Chumworathayi, Bandit Vargas Lejarza, Sandra Villegas Araya, Luis Garcia, Francisco Budihas, Scott R. Long, Rodney Katki, Hormuzd A. Herrero, Rolando Burk, Robert D. Jeronimo, Jose TI An Evaluation by Midwives and Gynecologists of Treatability of Cervical Lesions by Cryotherapy Among Human Papillomavirus-Positive Women SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Cervical intraepithelial neoplasia; Cryotherapy; Screen-and-treat; Human papillomavirus; Low-resource settings ID VISUAL INSPECTION; ACETIC-ACID; CANCER PREVENTION; CARE; MAGNIFICATION; NEOPLASIA; CYTOLOGY; TRIAL; PERU AB Objectives: To estimate efficacy of a visual triage of human papillomavirus (HPV)-positive women to either immediate cryotherapy or referral if not treatable (eg, invasive cancer, large precancers). Methods: We evaluated visual triage in the HPV-positive women aged 25 to 55 years from the 10,000-woman Guanacaste Cohort Study (n = 552). Twelve Peruvian midwives and 5 international gynecologists assessed treatability by cryotherapy using digitized high-resolution cervical images taken at enrollment. The reference standard of treatability was determined by 2 lead gynecologists from the entire 7-year follow-up of the women. Women diagnosed with histologic cervical intraepithelial neoplasia grade 2 or worse or 5-year persistence of carcinogenic HPV infection were defined as needing treatment. Results: Midwives and gynecologists judged 30.8% and 41.2% of women not treatable by cryotherapy, respectively (P < 0.01). Among 149 women needing treatment, midwives and gynecologists correctly identified 57.5% and 63.8% (P = 0.07 for difference) of 71 women judged not treatable by the lead gynecologists and 77.6% and 59.7% (P < 0.01 for difference) of 78 women judged treatable by cryotherapy. The proportion of women judged not treatable by a reviewer varied widely and ranged from 18.6% to 61.1%. Interrater agreement was poor with mean pairwise overall agreement of 71.4% and 66.3% and kappa's of 0.33 and 0.30 for midwives and gynecologists, respectively. Conclusions: In future "screen-and-treat" cervical cancer prevention programs using HPV testing and cryotherapy, practitioners will visually triage HPV-positive women. The suboptimal performance of visual triage suggests that screen-and-treat programs using cryotherapy might be insufficient for treating precancerous lesions. Improved, low-technology triage methods and/or improved safe and low-technology treatment options are needed. C1 [Gage, Julia C.] NCI, Hormonal & Reprod Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. [Cecilia Rodriguez, Ana; Herrero, Rolando] Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. [Adadevoh, Sydney] ReproHlth Consult, Accra, Ghana. [Alvarez Larraondo, Manuel J.] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Chumworathayi, Bandit] Khon Kaen Univ, Fac Med, Dept Obstet & Gynecol, Khon Kaen, Thailand. [Vargas Lejarza, Sandra] Mexico Hosp, San Jose, Costa Rica. [Villegas Araya, Luis] Enrique Baltodano Hosp, San Jose, Costa Rica. [Garcia, Francisco] Univ Arizona, Natl Ctr Excellence Womens Hlth, Tucson, AZ USA. [Budihas, Scott R.; Long, Rodney] Natl Lib Med, Commun Engn Branch, Bethesda, MD USA. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Burk, Robert D.] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Obstet Gynecol & Womens Hlth, Bronx, NY 10467 USA. [Jeronimo, Jose] Program Appropriate Technol Hlth, Seattle, WA USA. RP Gage, JC (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, DCEG, NIH, 6120 Executive Blvd,EPS,Room 5034B, Bethesda, MD 20892 USA. RI Khon Kaen University, Faculty of Medicine/A-3133-2009; Katki, Hormuzd/B-4003-2015 FU NCI NIH HHS [R01 CA078527, U01 CA078527, U01 CA078527-06] NR 20 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD MAY PY 2009 VL 19 IS 4 BP 728 EP 733 DI 10.1111/IGC.0b013e3181a48b99 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 457ZF UT WOS:000266976800040 PM 19509579 ER PT J AU Elstrand, MB Kleinberg, L Kohn, EC Trope, CG Davidson, B AF Elstrand, Mari Bunkholt Kleinberg, Lilach Kohn, Elise C. Trope, Claes G. Davidson, Ben TI Expression and Clinical Role of Antiapoptotic Proteins of the Bag, Heat Shock, and Bcl-2 Families in Effusions, Primary Tumors, and Solid Metastases in Ovarian Carcinoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE Ovarian carcinoma; Serous effusions; Apoptosis; Chemotherapy; Survival ID DEATH-DOMAINS; PROGNOSTIC-SIGNIFICANCE; DEFINING RESPONSE; POOR-PROGNOSIS; CELL-DEATH; FOLLOW-UP; CANCER; APOPTOSIS; SURVIVAL; P53 AB Cancer progression is associated with reduced apoptosis and increased proliferation. We hypothesized that upregulation of the Bag family Of Survival cochaperones and its molecular partners of the Bcl-2 and heat shock protein (HSP) families would correlate with disease progression and survival in Ovarian cancer. Bag-1, Bag-4, HSP27, HSP70, Bcl-2, and Bcl-X(L) expression was immunohistochemically analyzed in effusions (188) and patient-matched solid tumors (43 primary carcinomas, 81 solid metastases). Results were analyzed for anatomic site-related differences, and association with clinicopathologic parameters and survival. Bag-1, Bag-4, and HSP70 were detected in the tumor cell nuclei and cytoplasm, whereas HSP27, Bcl-2, and Bcl-X(L) had exclusively cytoplasmic localization. Antiapoptotic protein expression in effusions differed significantly from primary tumors and metastases. Cytoplasmic Bag-l (P=0.002), nuclear and cytoplasmic HSP70 (P<0.001), and Bcl-2 (P=0.001) expression was higher in primary carcinomas and solid metastases compared with effusions, whereas Bcl-XL (P=0.01), nuclear Bag-1 (P<0.001), nuclear Bag-4 (P=0.01), and cytoplasmic Bag-4 (P=0.002) were upregulated in effusions. Bcl-XL expression was associated with poor response to chemotherapy at diagnosis (P=0.02) and HSP27 expression was associated with high-grade tumors (P=0.01). increased cytoplasmic HSP70 staining in effusions correlated with poor overall survival for the entire cohort (P=0.01). In primary carcinomas, higher Bcl-2 expression correlated with worse overall (P=0.04) and progression-free (P=0.02) Survival. Antiapoptotic proteins are differentially expressed in effusions compared with solid tumors, whereas primary carcinomas and solid metastases have comparable expression patterns. HSP70 expression in effusions may be a prognostic marker of poor survival, with a similar role for Bcl-2 in primary carcinomas. C1 [Elstrand, Mari Bunkholt; Trope, Claes G.] Univ Hosp, Rikshosp, Norwegian Radium Hosp, Gynecol Oncol Sect,Div Obstet & Gynecol, N-0310 Oslo, Norway. [Kleinberg, Lilach; Davidson, Ben] Univ Hosp, Rikshosp, Norwegian Radium Hosp, Div Pathol, N-0310 Oslo, Norway. [Trope, Claes G.; Davidson, Ben] Univ Oslo, Fac Div Radiumhosp, Fac Med, Oslo, Norway. [Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Davidson, B (reprint author), Univ Hosp, Rikshosp, Norwegian Radium Hosp, Pathol Clin, N-0310 Oslo, Norway. EM ben.davidson@radiumhospitalet.no FU Norwegian Cancer Society; Southern Norway Health Region Research Fund; Research Fund at Radiumhospitalet FX Supported by the Norwegian Cancer Society, the Southern Norway Health Region Research Fund and the Research Fund at Radiumhospitalet. NR 55 TC 25 Z9 26 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD MAY PY 2009 VL 28 IS 3 BP 211 EP 221 DI 10.1097/PGP.0b013e31818b0f5e PG 11 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 436TI UT WOS:000265438600002 PM 19620938 ER PT J AU Engmann, C Matendo, R Kinoshita, R Ditekemena, J Moore, J Goldenberg, RL Tshefu, A Carlo, WA McClure, EM Bose, C Wright, LL AF Engmann, Cyril Matendo, Richard Kinoshita, Rinko Ditekemena, John Moore, Janet Goldenberg, Robert L. Tshefu, Antoinette Carlo, Waldemar A. McClure, Elizabeth M. Bose, Carl Wright, Linda L. TI Stillbirth and early neonatal mortality in rural Central Africa SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Africa; Early neonatal death; Fresh and macerated stillbirth; Low-income country ID DEVELOPING-COUNTRIES; PRENATAL-CARE; HEALTH; INTERVENTIONS; INTRAPARTUM; POPULATION; STATISTICS; MORBIDITY; SURVIVAL; DEATHS AB Objective: To develop a prospective perinatal registry that characterizes all deliveries, differentiates between stillbirths and early neonatal deaths (ENDs), and determines the ratio of fresh to macerated stillbirths in the northwest Democratic Republic of Congo. Method: Birth outcomes were obtained from 4 rural health districts. Results: A total of 8230 women consented, END rate was 32 deaths per 1000 live births, and stillbirth rate was 33 deaths per 1000 deliveries. The majority (75%) of ENDs and stillbirths occurred in neonates weighing 1500 g or more. Odds of stillbirth and END increased in mothers who were single or who did not receive prenatal care, and among premature, low birth weight, or male infants. The ratio of fresh to macerated stillbirths was 4:1. Conclusion: Neonates weighing 1500 g or more at birth represent a group with a high likelihood of survival in remote areas, making them potentially amenable to targeted intervention packages. The ratio of fresh to macerated stillbirths was approximately 10-fold higher than expected, suggesting a more prominent role for improved intrapartum obstetric interventions. (C) 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Engmann, Cyril] Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC 27599 USA. [Matendo, Richard; Ditekemena, John; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Kinoshita, Rinko] USAID, Kinshasa, Zaire. [Moore, Janet; McClure, Elizabeth M.] Res Triangle Inst, Res Triangle Pk, NC USA. [Goldenberg, Robert L.] Drexel Univ, Philadelphia, PA 19104 USA. [Carlo, Waldemar A.] Univ Alabama, Birmingham, AL USA. [Wright, Linda L.] Natl Inst Child Hlth & Dev, Bethesda, MD USA. RP Engmann, C (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, CB 7596,4th Floor,UNC Hosp, Chapel Hill, NC 27599 USA. EM cengmann@med.unc.edu FU National Institute of Child Health and Human Development [U01 HD043475]; Bill and Melinda Gates Foundation FX Funding was provided by grants from the National Institute of Child Health and Human Development (U01 HD043475) and the Bill and Melinda Gates Foundation. NR 25 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD MAY PY 2009 VL 105 IS 2 BP 112 EP 117 DI 10.1016/j.ijgo.2008.12.012 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 444GL UT WOS:000265968600006 PM 19201402 ER PT J AU Vareniuk, I Pacher, P Pavlov, IA Drel, VR Obrosova, IG AF Vareniuk, Igor Pacher, Pal Pavlov, Ivan A. Drel, Viktor R. Obrosova, Irina G. TI Peripheral neuropathy in mice with neuronal nitric oxide synthase gene deficiency SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE nerve conduction; neuronal nitric oxide synthase; nitrosative stress; peripheral diabetic neuropathy; streptozotocin-diabetic mouse ID PEROXYNITRITE DECOMPOSITION CATALYST; EXPERIMENTAL DIABETIC-NEUROPATHY; POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; NERVE-FIBER LOSS; FACTOR-KAPPA-B; NITROSATIVE STRESS; SPINAL-CORD; ALDOSE REDUCTASE; ENDOTHELIAL DYSFUNCTION; INCREASED EXPRESSION AB Evidence for the important role of the potent oxidant peroxynitrite in peripheral diabetic neuropathy and neuropathic pain is emerging. This study evaluated the contribution of neuronal nitric oxide synthase (nNOS) to diabetes-induced nitrosative stress in peripheral nerve and dorsal root ganglia, and peripheral nerve dysfunction and degeneration. Control and nNOS(-/-) mice were made diabetic with streptozotocin, and maintained for 6 weeks. Peroxynitrite injury was assessed by nitrotyrosine and poly(ADP-ribose) immunoreactivities. Peripheral diabetic neuropathy was evaluated by measurements of sciatic motor and hind-limb digital sensory nerve conduction velocities, thermal algesia, tactile allodynia, and intraepidermal nerve fiber density. Control nNOS(-/-) mice displayed normal motor nerve conduction velocity and thermal response latency, whereas sensory nerve conduction velocity was slightly lower compared with non-diabetic wild-type mice, and tactile response threshold and intraepidermal nerve fiber density were reduced by 47 and 38%, respectively. Both diabetic wild-type and nNOS(-/-) mice displayed enhanced nitrosative stress in peripheral nerve. In contrast to diabetic wild-type mice, diabetic nNOS(-/-) mice had near normal nitrotyrosine and poly(ADP-ribose) immunofluorescence in dorsal root ganglia. Both diabetic wild-type and nNOS(-/-) mice developed motor and sensory nerve conduction velocity deficits and thermal hypoalgesia although nNOS gene deficiency slightly reduced severity of the three disorders. Tactile response thresholds were similarly decreased in control and diabetic nNOS(-/-) mice compared with non-diabetic wild-type mice. Intraepidermal nerve fiber density was lower by 27% in diabetic nNOS(-/-) mice compared with the corresponding nondiabetic group, and by 20% in diabetic nNOS(-/-) mice compared with diabetic wild-type mice. In conclusion, nNOS is required for maintaining the normal peripheral nerve function and small sensory nerve fibre innervation. nNOS gene deficiency does not protect from development of nerve conduction deficit, sensory neuropathy and intraepidermal nerve fiber loss. C1 [Vareniuk, Igor; Pavlov, Ivan A.; Drel, Viktor R.; Obrosova, Irina G.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Obrosova, IG (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM obrosoig@pbrc.edu RI Pacher, Pal/B-6378-2008; Drel, Viktor/G-8883-2016 OI Pacher, Pal/0000-0001-7036-8108; Drel, Viktor/0000-0003-4542-0132 FU American Diabetes Association Research [7-05-RA-102]; Juvenile Diabetes Research Foundation [1-2005-223]; National Institutes of Health [DK 071566-01]; National Institutes of Health/National Institute of Alcohol Abuse and Alcoholism FX The study was supported by the American Diabetes Association Research Grant 7-05-RA-102, the Juvenile Diabetes Research Foundation International Grant 1-2005-223, the National Institutes of Health Grant DK 071566-01 (all to I.G.O.), and the Intramural Research Program of the National Institutes of Health/National Institute of Alcohol Abuse and Alcoholism (to P.P.). NR 57 TC 20 Z9 21 U1 0 U2 0 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAY PY 2009 VL 23 IS 5 BP 571 EP 580 DI 10.3892/ijmm_00000166 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 434FU UT WOS:000265261400001 PM 19360314 ER PT J AU Khairova, RA Machado-Vieira, R Du, J Manji, HK AF Khairova, Rushaniya A. Machado-Vieira, Rodrigo Du, Jing Manji, Husseini K. TI A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Bipolar disorder; cytokines; depression; inflammation; synaptic plasticity; treatment ID TUMOR-NECROSIS-FACTOR; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; INTERLEUKIN-1 RECEPTOR ANTAGONIST; FACTOR-ALPHA PRODUCTION; CHRONIC HEPATITIS-C; GLIAL TNF-ALPHA; GYRUS IN-VITRO; NF-KAPPA-B; BIPOLAR DISORDER AB A growing body of data suggests that hyperactivation of the immune system has been implicated in the pathophysiology of major depressive disorder (MDD). Several pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been found to be significantly increased in patients with MDD. This review focuses on these two cytokines based on multiple lines of evidence from genetic, animal behaviour, and clinical studies showing that altered levels of serum TNF-alpha and IL-1 are associated with increased risk of depression, cognitive impairments, and reduced responsiveness to treatment. In addition, recent findings have shown that centrally expressed TNF-alpha and IL-1 play a dual role in the regulation of synaptic plasticity. In this paper, we review and critically appraise the mechanisms by which cytokines regulate synaptic and neural plasticity, and their implications for the pathophysiology and treatment of MDD. Finally, we discuss the therapeutic potential of anti-inflammatory-based approaches for treating patients with severe mood disorders. This is a promising field for increasing our understanding of the mechanistic interaction between the immune system, synaptic plasticity, and antidepressants, and for the ultimate development of novel and improved therapeutics for severe mood disorders. C1 [Khairova, Rushaniya A.; Machado-Vieira, Rodrigo; Du, Jing; Manji, Husseini K.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Bldg 35 1C912, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov RI Du, Jing/A-9023-2012; MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health (NIMH); National Institutes of Health (NIH); Department of Health and Human Services (DHHS) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH), National Institutes of Health (NIH), Department of Health and Human Services (DHHS). This work was completed under the auspices of the Intramural Program of the NIMH. Dr Manji is now at Johnson and Johnson PRD. We thank Ioline Henter for outstanding editorial assistance. NR 201 TC 118 Z9 126 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD MAY PY 2009 VL 12 IS 4 BP 561 EP 578 DI 10.1017/S1461145709009924 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 449BM UT WOS:000266305800012 PM 19224657 ER PT J AU Faruque, MU Millis, RM Dunston, GM Kwagyan, J Bond, V Rotimi, CN Davis, T Christie, R Campbell, AL AF Faruque, M. U. Millis, R. M. Dunston, G. M. Kwagyan, J. Bond, V., Jr. Rotimi, C. N. Davis, T. Christie, R. Campbell, A. L. TI Association of GNB3 C825T Polymorphism with Peak Oxygen Consumption SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article DE GNB3; cardiorespiratory fitness; heart rate variability; African-Americans; autonomic modulation ID HEART-RATE-VARIABILITY; PROTEIN BETA-3 SUBUNIT; HERITAGE FAMILY; CARDIORESPIRATORY FITNESS; 825T ALLELE; CARDIOVASCULAR-DISEASE; SEQUENCE VARIATION; EXERCISE CAPACITY; AEROBIC FITNESS; HYPERTENSION AB The C825T single nucleotide polymorphism (SNIP) in the guanine nucleotide-binding protein, beta polypeptide 3 (GNB3) gene gives rise to a splice variant, GNB3s that has enhanced G protein activation and signal transduction activity. This variant has been reported to be associated with cardiovascular disease, diabetes and obesity. We studied this SNP in 95 healthy 18 to 30 year-old African American university students to determine its association with aerobic capacity and cardiorespiratory fitness as measured by peak oxygen consumption (VO(2)peak). We also tested the effect of heart rate variability (HRV) as an independent predictor Of VO(2)peak. We tested the association of the SNIP and HRV with VO(2)peak in a multivariate regression analysis with appropriate adjustments of covariates, under dominant and recessive models. We found a significant independent association of the 825T allele with VO(2)peak under the dominant model (beta-coef. = -0.101, P = 0.0442). We also observed that HRV marginally influenced VO(2)peak. This finding suggests that GNB3 C825T polymorphism is associated with VO(2)peak which is influenced by autonomic modulation of heart rate in African Americans. C1 [Faruque, M. U.] Howard Univ, Natl Human Genome Ctr, Washington, DC 20060 USA. [Millis, R. M.] Howard Univ, Dept Physiol & Biophys, Washington, DC 20060 USA. [Dunston, G. M.] Howard Univ, Dept Microbiol, Washington, DC 20060 USA. [Kwagyan, J.] Howard Univ, Dept Community & Family Med, Washington, DC 20060 USA. [Bond, V., Jr.; Christie, R.] Howard Univ, Dept Hlth Human Performance & Leisure Studies, Washington, DC 20060 USA. [Rotimi, C. N.] NHGRI, NIH, Bethesda, MD 20892 USA. [Davis, T.] Howard Univ, Dept Genet & Human Genet, Washington, DC 20060 USA. [Campbell, A. L.] Howard Univ, Dept Psychol, Washington, DC 20060 USA. RP Faruque, MU (reprint author), Howard Univ, Natl Human Genome Ctr, 2041 Georgia Ave NW, Washington, DC 20060 USA. EM mfaruque@howard.edu FU RCMI Program, Division of Research Infrastructure, National Center for Research Resources, National Institutes of Health [2 G12 RR003048]; Howard University Mordecai Wyatt Johnson Fund FX The authors wish to acknowledge the DNA Genotek Inc., Ontario, Canada for providing the ORAgene DNA Self-Collection Kit. This study was supported by grant 2 G12 RR003048 from the RCMI Program, Division of Research Infrastructure, National Center for Research Resources, National Institutes of Health and a grant from the Howard University Mordecai Wyatt Johnson Fund. NR 37 TC 8 Z9 8 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0172-4622 J9 INT J SPORTS MED JI Int. J. Sports Med. PD MAY PY 2009 VL 30 IS 5 BP 315 EP 319 DI 10.1055/s-0029-1202259 PG 5 WC Sport Sciences SC Sport Sciences GA 447SK UT WOS:000266211900002 PM 19301222 ER PT J AU Jeon, DS Kim, DH Kang, HS Hwang, SH Min, JH Kim, JH Sung, NM Carroll, MW Park, SK AF Jeon, D. S. Kim, D. H. Kang, H. S. Hwang, S. H. Min, J. H. Kim, J. H. Sung, N. M. Carroll, M. W. Park, S. K. TI Survival and predictors of outcomes in non-HIV-infected patients with extensively drug-resistant tuberculosis SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; multidrug-resistant; extensively drug-resistant tuberculosis ID MULTIDRUG-RESISTANT; EFFICACY; TB AB SETTING: A tuberculosis (TB) referral hospital in South Korea. OBJECTIVE: To evaluate predictors of treatment outcomes and survival among non-human immunodeficiency virus (HIV) infected patients with extensively drug-resistant TB (XDR-TB). DESIGN: Patients who were diagnosed with XDR-TB at the National Masan Tuberculosis Hospital from January 2001 to December 2005 were included in this study. We conducted a retrospective review of their medical records and mortality data. RESULTS: A total of 176 non-HIV-infected patients with XDR-TB were included. TB-related mortality was 48% (84/1.76), and the median survival time from the diagnosis date of XDR-TB was 51 months (range 0127, 95%CI 32.53-69.47). Cure and treatment completion were classified as favourable outcome and treatment failure, death during treatment and default as poor outcome. Previous TB treatment with second-line drugs (aOR 2.76, 95%CI 1.02-7.44) and cavitary disease (aOR 3.01, 95%CI 1.12-8.08) were independent risk factors for poor outcome. Use of linezolid (aOR 0.10, 95%CI 0.01-0.69) and surgical resection (aOR 0.18, 95%CI 0.04-0.78) were associated with favourable outcome. CONCLUSION: There was high mortality in non-HIV-infected patients with XDR-TB at a TB referral hospital in South Korea. Adjunctive surgical treatment and linezolid improved the outcome for selected patients with XDR-TB. C1 [Jeon, D. S.; Kim, D. H.; Kang, H. S.; Hwang, S. H.; Min, J. H.; Kim, J. H.; Sung, N. M.; Park, S. K.] Natl Masan TB Hosp, Masan 631710, South Korea. [Jeon, D. S.; Park, S. K.] Int TB Res Ctr, Masan, South Korea. [Carroll, M. W.] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA. RP Jeon, DS (reprint author), Natl Masan TB Hosp, 486 Gapo Dong, Masan 631710, South Korea. EM sooli10kr@yahoo.co.kr NR 21 TC 27 Z9 28 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAY PY 2009 VL 13 IS 5 BP 594 EP 600 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 436OY UT WOS:000265424900012 PM 19383192 ER PT J AU Richter, HE Burgio, KL Chai, TC Kraus, SR Xu, Y Nyberg, L Brubaker, L AF Richter, Holly E. Burgio, Kathryn L. Chai, Toby C. Kraus, Stephen R. Xu, Yan Nyberg, Lee Brubaker, Linda TI Predictors of outcomes in the treatment of urge urinary incontinence in women SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Urge urinary incontinence; Randomized trial; Predictors of outcome ID PELVIC ORGAN PROLAPSE; OVERACTIVE BLADDER; BEHAVIORAL TREATMENT; DRUG-TREATMENT; OLDER WOMEN; EFFICACY; THERAPY; TOLTERODINE; DYSFUNCTION; MANAGEMENT AB Women with urge predominant urinary incontinence received active intervention (drug therapy alone or combined with behavioral therapy) for 10 weeks, then stopped all therapy and were followed for 6 months more. In this planned secondary analysis, we aimed to identify predictors of therapeutic success at 10 weeks (a parts per thousand yen70% reduction in incontinence) and of ability to discontinue treatment and sustain improvements 6 months later. Using data from 307 women, we performed logistic regression to identify predictors for outcomes described above. After controlling for group, only younger age was associated with short-term success (OR 0.8, 95% CI 0.66, 0.96). At 6 months, controlling for group and short-term outcome, only greater anterior vaginal wall prolapse was associated with successful discontinuation (POP-Q point Aa; OR 1.33, 95% CI 1.03, 1.7). These findings are not of sufficient strength to justify withholding conservative therapies but might be used to promote realistic expectations when counseling patients. C1 [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Div Womens Pelv Med & Reconstruct Surg, Birmingham, AL 35233 USA. [Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Dept Vet Affairs Med Ctr, Birmingham, AL USA. [Chai, Toby C.] Univ Maryland, Baltimore, MD 21201 USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Xu, Yan] New England Res Inst, Watertown, MA 02172 USA. [Nyberg, Lee] Natl Inst Diabet & Digest & Kidney Dis, Bethesda, MD USA. [Brubaker, Linda] Loyola Univ, Chicago, IL 60611 USA. RP Richter, HE (reprint author), Univ Alabama, Dept Obstet & Gynecol, Div Womens Pelv Med & Reconstruct Surg, Birmingham, AL 35233 USA. EM hrichter@uab.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, 60401]; National Institute of Child Health and Human Development; Office of Research in Women's Health, National Institutes of Health FX This trial is registered at Clinicaltrials. gov NCT00064662. For a list of UITN investigators, see Appendix 1. NR 30 TC 5 Z9 5 U1 1 U2 3 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD MAY PY 2009 VL 20 IS 5 BP 489 EP 497 DI 10.1007/s00192-009-0805-1 PG 9 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 426JA UT WOS:000264702600003 PM 19183825 ER PT J AU Wojciechowski, R Stambolian, D Ciner, E Ibay, G Holmes, TN Bailey-Wilson, JE AF Wojciechowski, Robert Stambolian, Dwight Ciner, Elise Ibay, Grace Holmes, Taura N. Bailey-Wilson, Joan E. TI Genomewide Linkage Scans for Ocular Refraction and Meta-analysis of Four Populations in the Myopia Family Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HIGH-GRADE MYOPIA; OLD ORDER AMISH; WIDE SCAN; GENETIC-LINKAGE; SUSCEPTIBILITY LOCUS; CHROMOSOME 22Q12; EYE DISEASE; NEAR-WORK; SIB-PAIR; ERRORS AB PURPOSE. Genomewide linkage scans were performed in Caucasian (CAUC) and Old Order Amish (OOA) families to identify genomic regions containing genes responsible for refractive error control. We also performed a meta-analysis by combining these results with our previous linkage results from Ashkenazi Jewish (ASHK) and African American (AFRAM) families. METHODS. Two hundred seventy-one CAUC and 411 OOA participants (36 and 61 families, respectively) were recruited to participate in the Myopia Family Study. Recruitment criteria were designed to enrich the sample for multiplex myopic families. Genomewide, model-free, multipoint linkage analyses were performed separately for each population by using > 370 microsatellite markers. Empirical significance levels were determined via gene-dropping simulations. A meta-analysis was performed by combining linkage results from the CAUC, OOA, AFRAM, and ASHK samples, and results were compared to previously reported loci for myopia and refraction. RESULTS. Suggestive evidence of linkage was found at 12q24 (LOD = 4.583, P = 0.00037) and 4q21 (LOD = 2.72, P = 0.0028) in the CAUC sample and at 5qter (LOD = 3.271, P = 0.0014) in the OOA. Meta-analysis linkage results were largely driven by population-specific signals from ASHK and AFRAM families. The meta-analysis showed suggestive evidence of linkage to 4q21-22 (meta-P = 0.00214) adjacent to the previously reported MYP9 and MYP11 loci. CONCLUSIONS. The results showed suggestive evidence of linkage of ocular refraction to 12q24 and 4q21 in CAUC and to 5qter in OOA families. The meta-analysis supports the view that several genes play a role in refractive development across populations. In MFS families, four broad genomic regions (on 1p, 4q, 7p, and 12q) most likely contain genes that influence ocular refraction. (Invest Ophthalmol Vis Sci. 2009;50:2024-2032) DOI:10.1167/iovs.08-2848 C1 [Wojciechowski, Robert; Ibay, Grace; Holmes, Taura N.; Bailey-Wilson, Joan E.] Natl Human Genome Res Inst NIH, Inherited Dis Res Branch, Baltimore, MD 21231 USA. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. [Ciner, Elise] Penn Coll Optometry, Inst Eye, Philadelphia, PA 19141 USA. RP Wojciechowski, R (reprint author), Natl Human Genome Res Inst NIH, Inherited Dis Res Branch, Johns Hopkins Bayview Campus,333 Cassell Dr,Suite, Baltimore, MD 21231 USA. EM robwoj@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski, Robert/0000-0002-9593-4652 FU U. S. Public Health National Eye Institute [EY12226]; National Human Genome Research Institute, National Institutes of Health FX Supported in part by U. S. Public Health National Eye Institute Grant EY12226 (DS, EC) and funds from the intramural program of the National Human Genome Research Institute, National Institutes of Health (JEB-W, GI, TNH, RW). RW received a William C. Ezell-CIBA Vision Fellowship from the American Optometric Foundation. Genotyping services were provided by the Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University (contract number N01-HG-65403). NR 65 TC 16 Z9 17 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2009 VL 50 IS 5 BP 2024 EP 2032 DI 10.1167/iovs.08-2848 PG 9 WC Ophthalmology SC Ophthalmology GA 436YC UT WOS:000265451000008 PM 19151385 ER PT J AU Guigon, CJ Cheng, SY AF Guigon, Celine J. Cheng, Sheue-yann TI Novel Oncogenic Actions of TR beta Mutants in Tumorigenesis SO IUBMB LIFE LA English DT Article DE thyroid hormone receptor mutants; thyroid cancer; pituitary tumor; nongenomic action; TR beta PV; phosphatidylinositol 3-kinase; pituitary tumor transforming gene ID THYROID-HORMONE RECEPTOR; SECRETING PITUITARY-TUMOR; CLEAR-CELL CARCINOMA; HUMAN BREAST-CANCER; MOUSE MODEL; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVITY; HEPATOCELLULAR-CARCINOMA; CATENIN DEGRADATION; ANDROGEN RECEPTOR AB The thyroid hormone, T3, plays important roles in metabolism, growth, and differentiation. Germline mutations in thyroid hormone receptor beta (TR beta) have been identified in many individuals with resistance to thyroid hormone, a syndrome of reduced sensitivity to T3. A close association of somatic mutations of TR beta with several human cancers has become increasingly apparent, but how TR beta mutants could be involved in the carcinogenesis in vivo has not been addressed. The creation of a mouse model (TR beta(PV/PV) mouse) that harbors a knockin mutation of TR beta (denoted TR beta PV) has facilitated the study of the molecular actions of TR beta mutants in vivo. The striking phenotype of thyroid cancer and the development of pituitary tumors exhibited by TR beta(PV/PV) mice have uncovered novel functions of a TR beta mutant in tumorigenesis. It led to the important findings that the oncogenic action of TR beta PV is mediated by both genomic and nongenomic actions to after gene expression and signaling, pathways activity. (C) 2009 IUBMB IUBMB Life, 61(5): 528-536, 2009 C1 [Guigon, Celine J.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM cheng@mail.nih.gov FU Intramural Research Program of Center for Cancer Research; National Cancer Institute; National Institutes of Health FX We thank all colleagues and collaborators who have contributed to the work described in this review. The present research was supported by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, and National Institutes of Health. NR 66 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD MAY PY 2009 VL 61 IS 5 BP 528 EP 536 DI 10.1002/iub.180 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 440RB UT WOS:000265716300008 PM 19391168 ER PT J AU Li, DB Fayad, ZA Bluemke, DA AF Li, Debiao Fayad, Zahi A. Bluemke, David A. TI Can Contrast-Enhanced Cardiac Magnetic Resonance Assess Inflammation of the Coronary Wall? SO JACC-CARDIOVASCULAR IMAGING LA English DT Editorial Material DE coronary arteries; atherosclerosis; cardiac magnetic resonance; inflammation; contrast-enhanced imaging ID HIGH-RESOLUTION MRI; ATHEROSCLEROTIC PLAQUES; ARTERIAL-WALL; DISEASE C1 [Li, Debiao] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA. [Li, Debiao] Northwestern Univ, Dept Biomed Engn, Chicago, IL 60611 USA. [Fayad, Zahi A.] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Li, DB (reprint author), Northwestern Univ, Dept Radiol, Suite 1600,737 N Michigan Ave, Chicago, IL 60611 USA. EM d-li2@northwestern.edu OI Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [ZIA CL090019-01, ZIA EB000072-01]; NHLBI NIH HHS [R01 HL038698, R01 HL038698-16] NR 21 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD MAY PY 2009 VL 2 IS 5 BP 589 EP 591 DI 10.1016/j.jcmg.2009.03.006 PG 3 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 725NW UT WOS:000287653200010 PM 19442945 ER PT J AU Kim, LJ King, SB Kent, K Brooks, MM Kip, KE Abbott, JD Jacobs, AK Rihal, C Hueb, WA Alderman, E Sing, IRP Attubato, MJ Feit, F AF Kim, Lauren J. King, Spencer B., III Kent, Kenneth Brooks, Maria Mori Kip, Kevin E. Abbott, J. Dawn Jacobs, Alice K. Rihal, Charanjit Hueb, Whady A. Alderman, Edwin Sing, Ivan R. Pena Attubato, Michael J. Feit, Frederick CA BARI 2D Bypass Angioplasty Revascu TI Factors Related to the Selection of Surgical Versus Percutaneous Revascularization in Diabetic Patients With Multivessel Coronary Artery Disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) Trial SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE revascularization selection; diabetes; percutaneous coronary intervention; coronary artery bypass graft surgery ID PRACTICE GUIDELINES COMMITTEE; ACUTE MYOCARDIAL-INFARCTION; SIROLIMUS-ELUTING STENTS; ASSOCIATION TASK-FORCE; ACC/AHA GUIDELINES; AMERICAN-COLLEGE; RANDOMIZED-TRIAL; UNITED-STATES; MELLITUS; OUTCOMES AB Objectives We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. Background Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. Methods In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. Results Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >= 70% (OR: 2.86), proximal left anterior descending stenosis >= 50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >= 65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). Conclusions The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305) (J Am Coll Cardiol Intv 2009;2:384-92) (C) 2009 by the American College of Cardiology Foundation C1 [Attubato, Michael J.; Feit, Frederick] NYU, Sch Med, New York, NY 10016 USA. [Alderman, Edwin; Sing, Ivan R. Pena] Stanford Univ, Stanford, CA 94305 USA. [Hueb, Whady A.] Univ Sao Paulo, Inst Heart, Sao Paulo, Brazil. [Rihal, Charanjit] Mayo Clin, Rochester, MN USA. [Jacobs, Alice K.] Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. [Abbott, J. Dawn] Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. [Kip, Kevin E.] Univ S Florida, Tampa, FL USA. [Brooks, Maria Mori] Univ Pittsburgh, Pittsburgh, PA USA. [Kent, Kenneth] Washington Hosp Ctr, Washington, DC 20010 USA. [King, Spencer B., III] St Josephs Heart & Vasc Inst, Atlanta, GA USA. [Kim, Lauren J.] NIA, Bethesda, MD 20892 USA. RP Feit, F (reprint author), NYU, Sch Med, Dept Med, Div Cardiol,Tisch Hosp, Room H576,560 1st Ave, New York, NY 10016 USA. EM frederick.feit@med.nyu.edu RI Hueb, Whady/A-7919-2013; OI Brooks, Maria/0000-0002-2030-7873; Attubato, Michael/0000-0002-2772-9382 FU National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases [U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804]; GlaxoSmithKline; Bristol-Myers Squibb Medical Imaging, Inc.; Astellas Pharma US, Inc.; Merck Co., Inc.; Abbott Laboratories, Inc.; Pfizer, Inc.; Abbott Laboratories Ltd.; MediSense Products; Bayer Diagnostics; Becton, Dickinson and Company; J. R. Carlson Laboratories, Inc.; Centocor, Inc.; Eli Lilly and Company; LipoScience, Inc.; Merck Sante; Novartis Pharmaceuticals Corporation; Novo Nordisk, Inc. FX The BARI 2D study is funded by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases (U01 HL061744, U01 HL061746, U01 HL061748, U01 HL063804). The BARI 2D study receives significant supplemental funding from GlaxoSmithKline; Bristol-Myers Squibb Medical Imaging, Inc.; Astellas Pharma US, Inc.; Merck & Co., Inc.; Abbott Laboratories, Inc.; and Pfizer, Inc.; and generous support from Abbott Laboratories Ltd.; MediSense Products; Bayer Diagnostics; Becton, Dickinson and Company; J. R. Carlson Laboratories, Inc.; Centocor, Inc.; Eli Lilly and Company; LipoScience, Inc.; Merck Sante; Novartis Pharmaceuticals Corporation; and Novo Nordisk, Inc. Dr. Feit is a major shareholder of Eli Lilly and Novartis. A complete list of the BARI 2D Study Group has been published previously in reference 22. Morton Kern, MD, acted as Guest Editor for this paper. NR 27 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2009 VL 2 IS 5 BP 384 EP 392 DI 10.1016/j.jcin.2009.01.009 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 613HW UT WOS:000278971000002 PM 19463459 ER PT J AU Gilbert, DG Zuo, YT Rabinovich, NE Riise, H Needham, R Huggenvik, JI AF Gilbert, David G. Zuo, Yantao Rabinovich, Norka E. Riise, Hege Needham, Rachel Huggenvik, Jodi I. TI Neurotransmission-Related Genetic Polymorphisms, Negative Affectivity Traits, and Gender Predict Tobacco Abstinence Symptoms Across 44 Days With and Without Nicotine Patch SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the Society-for-Research-in-Nicotine-and-Tobacco CY FEB 21-24, 2007-2008 CL Austin, TX SP Soc Res Nicotine & Tobacco DE nicotine replacement therapy; smoking cessation; serotonin transporter; DRD2 genotype; negative affect ID SMOKING WITHDRAWAL DYNAMICS; SEROTONIN TRANSPORTER GENE; DEPRESSIVE TRAITS; CESSATION; PERSONALITY; DEPENDENCE; NEUROTICISM; MOOD; ASSOCIATION; DOPAMINE AB Genetic and personality trait moderators of tobacco abstinence-symptom trajectories were assessed in a highly controlled study. Based on evidence suggesting their importance in stress reactivity and smoking, moderators studied were serotonin transporter gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) polymorphisms and personality traits related to negative affect (NA). Smokers were randomly assigned to quit smoking with nicotine or placebo patches. Financial incentives resulted in 80% verified abstinence across the 44-day study. Individuals with I or 2 short alleles of 5-HTTLPR (S carriers) experienced larger increases in NA symptoms than did those without a short allele. Nicotine replacement therapy (NRT) alleviated anxiety only in S carriers. NRT reduced NA to a greater extent in DRD2 A I carriers than in A2A2 individuals during the 1st 2 weeks of treatment (when on the 21-mg patch); however, A1 carriers experienced a renewal of NA symptoms when switched to the 7-mg patch and when off the patch, while A2A2 individuals continued to benefit from NRT. The results suggest that the effects of genotype and treatment may vary across different durations of abstinence, treatment doses, and genotypes. C1 [Gilbert, David G.; Rabinovich, Norka E.; Riise, Hege; Needham, Rachel] So Illinois Univ, Dept Psychol, Carbondale, IL 62901 USA. [Zuo, Yantao] Natl Inst Drug Abuse & Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD USA. [Huggenvik, Jodi I.] So Illinois Univ, Dept Physiol, Carbondale, IL 62901 USA. [Huggenvik, Jodi I.] So Illinois Univ, Sch Med, Carbondale, IL 62901 USA. RP Gilbert, DG (reprint author), So Illinois Univ, Dept Psychol, Mailcode 6502, Carbondale, IL 62901 USA. EM dgilbert@siu.edu OI Rabinovich, Norka/0000-0002-9917-7054 FU NIDA NIH HHS [R01 DA012289, R01 DA012289-02, R01 DA12289] NR 63 TC 18 Z9 19 U1 4 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 2009 VL 118 IS 2 BP 322 EP 334 DI 10.1037/a0015382 PG 13 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 443EP UT WOS:000265893300007 PM 19413407 ER PT J AU Iannotti, RJ Kogan, MD Janssen, I Boyce, WF AF Iannotti, Ronald J. Kogan, Michael D. Janssen, Ian Boyce, William F. TI Patterns of Adolescent Physical Activity, Screen-Based Media Use, and Positive and Negative Health Indicators in the US and Canada SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Physical activity; Sedentary behavior; Screen-based media use; Quality of life; Physical health status; Quality of family relationships; Quality of peer relationships; Health complaints; Substance use ID MIDDLE-SCHOOL-CHILDREN; SUBSTANCE USE; BEHAVIOR; SPORT; SMOKING; PARTICIPATION; TELEVISION; CIGARETTE; AMERICAN; EXERCISE AB Purpose: To examine: (1) how adolescent physical activity (PA) and screen-based media use (SBM) relate to physical and social health indicators, and (2) crossnational differences in these relationships. Methods: Essentially identical questions and methodologies were used in the Health Behavior in School-Aged Children cross-sectional surveys of nationally representative samples of American (N = 14,818) and Canadian (N = 7266) students in grades 6 to 10. Items included questions about frequency of PA, SBM, positive health indicators (health status, self-image, quality of life, and quality of family and peer relationships), and negative health indicators (health complaints, physical aggression, smoking, drinking, and marijuana use). Results: In regression analyses controlling for age and gender, positive health indicators were uniformly positively related to PA while two negative health indicators were negatively related to PA. However, PA was positively related to physical aggression. The pattern for SBM was generally the opposite; SBM was negatively related to most positive health indices and positively related to several of the negative health indicators. The notable exception was that SBM was positively related to the quality of peer relationships. Although there were crossnational differences in the strength of some relationships, these patterns were essentially replicated in both countries. Conclusions: Surveys of nationally representative samples of youth in two countries provide evidence of positive physical and social concomitants of PA and negative concomitants of SBM. These findings suggest potential positive consequences of increasing PA and decreasing SBM in adolescents and provide further justification for such efforts. (C) 2009 Society for Adolescent Medicine. All fights reserved. C1 [Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Baltimore, MD USA. [Kogan, Michael D.] US Hlth Resources & Serv Adm, Maternal & Child Hlth Bur, Rockville, MD 20857 USA. [Boyce, William F.] Queens Univ, Dept Epidemiol & Community Hlth, Fac Educ, Kingston, ON, Canada. [Janssen, Ian] Queens Univ, Sch Phys & Hlth Educ, Kingston, ON, Canada. [Boyce, William F.] Queens Univ, Fac Educ, Social Program Evaluat Grp, Kingston, ON, Canada. RP Iannotti, RJ (reprint author), 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. EM iannottr@mail.nih.gov RI Janssen, Ian/B-7700-2009; Price, Katie/H-1931-2012 FU Maternal and Child Health Bureau of the Health Resources and Services Administration; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Health Canada; Queen's University FX The 2001-2002 U.S. HBSC survey was supported by the Maternal and Child Health Bureau of the Health Resources and Services Administration and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The 2001-2002 Canadian HBSC survey was supported by Health Canada and Queen's University. The WHO-HBSC is a WHO/Euro collaborative study. International Coordinator of the 2001/02 study: Candace Currie, University of Edinburgh, Scotland; Data Bank Manager: Oddrun Samdal, University of Bergen, Norway. NR 36 TC 87 Z9 89 U1 0 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 2009 VL 44 IS 5 BP 493 EP 499 DI 10.1016/j.jadohealth.2008.10.142 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 436OP UT WOS:000265424000012 PM 19380098 ER PT J AU Senthilselvan, A Dosman, JA Chenard, L Burch, LH Predicala, BZ Sorowski, R Schneberger, D Hurst, T Kirychuk, S Gerdts, V Cormier, Y Rennie, DC Schwartz, DA AF Senthilselvan, Ambikaipakan Dosman, James A. Chenard, Liliane Burch, Lauranell H. Predicala, Bernardo Z. Sorowski, Randine Schneberger, David Hurst, Tom Kirychuk, Shelley Gerdts, Volker Cormier, Yvon Rennie, Donna C. Schwartz, David A. TI Toll-like receptor 4 variants reduce airway response in human subjects at high endotoxin levels in a swine facility SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Airway hyperresponsiveness; blood counts; cytokines; endotoxin; gene-environment interaction; lung function; swine confinement facility; Toll-like receptor 4 variants ID GENE-ENVIRONMENT INTERACTIONS; LUNG-FUNCTION DECLINE; SOLUBLE CD14 LEVELS; SERUM IGE LEVELS; CONFINEMENT BUILDINGS; PIG FARMERS; PULMONARY-FUNCTION; DUST; POLYMORPHISMS; EXPOSURE AB Background: Toll-like receptor 4 (TLR4) variants have been shown to reduce the respiratory responses to inhaled LPS in controlled experiments among healthy volunteers. Objective: We sought to investigate whether naive subjects with TLR4 variants showed reduced respiratory response to a complex aerosol including endotoxin as a major constituent. Methods: Twenty-nine nonsmoking, nonatopic healthy subjects with TLR4 299/399 polymorphisms and 29 age- and sex-matched, wild-type TLR4 control subjects were exposed for 5 hours each in a noncontaminated environment (baseline day) and in a swine confinement facility (exposure day). There were 16 men and 13 women in each of the 2 age- and sex-matched groups. Results: TLR4 polymorphic subjects who were exposed to high endotoxin levels (>= 1550 EU/m(3)) had less reduction in the percentage across-shift change in FEV(1) from baseline than did wild-type subjects exposed to similar endotoxin levels. Among subjects exposed to higher endotoxin levels, the mean differences in the percentage across-shift changes between baseline and exposure days were significantly less in TLR4 polymorphic subjects compared with those seen in wild-type subjects in FEV(1) (-8.48% +/- 1.52% [mean +/- SE] vs -11.46% +/- 1.79%, P = .001), forced expiratory flow between 25% and 75% of forced vital capacity (-18.30% +/- 1.99% vs -24.14% +/- 3.28%, P = .009), and FEV(1)/forced vital capacity ratio (-5.40% +/- 0.56% vs -8.53% +/- 1.51%, P = .04). These patterns were not observed in IL-6 levels from serum and nasal lavage fluid, IL-8 levels from nasal lavage fluid, white blood cell counts, or blood differential counts. Conclusion: The association between TLR4 variants and reduced airway responsiveness to inhaled particulate was observed at high endotoxin concentrations, creating the possibility of certain threshold phenomena for the apparent protective effect of TLR4 variants. (J Allergy Clin Immunol 2009;123:1034-40.) C1 [Senthilselvan, Ambikaipakan] Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, Edmonton, AB T6G 2G3, Canada. [Dosman, James A.; Chenard, Liliane; Sorowski, Randine; Schneberger, David; Kirychuk, Shelley; Rennie, Donna C.] Univ Saskatchewan, Candian Ctr Hlth & Safety Agr, Saskatoon, SK, Canada. [Gerdts, Volker] Univ Saskatchewan, Vaccine & Infect Dis Org, Saskatoon, SK, Canada. [Burch, Lauranell H.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Predicala, Bernardo Z.] Prairie Swine Ctr Inc, Saskatoon, SK, Canada. [Hurst, Tom] Univ Saskatchewan, Dept Med, Saskatoon, SK S7N 0W0, Canada. [Cormier, Yvon] Univ Laval, Quebec City, PQ, Canada. [Schwartz, David A.] Natl Jewish Hlth, Denver, CO USA. RP Senthilselvan, A (reprint author), Univ Alberta, Sch Publ Hlth, Dept Publ Hlth Sci, 13-106B Clin Sci Bldg, Edmonton, AB T6G 2G3, Canada. EM sentil@ualberta.ca FU Advancing Canadian Agriculture and Agri-Food Saskatchewan; National Science and Engineering Research Council (Canada); Saskatchewan Agriculture Development Fund; Alberta Agriculture and Food Council; Canadian Institutes for Health Research; Bill & Melinda Gates Foundation; Alberta Agriculture Funding Consortium; Canadian Lung Association FX Disclosure of potential conflict of interest: B. Predicala has received research support from Advancing Canadian Agriculture and Agri-Food Saskatchewan, the National Science and Engineering Research Council (Canada), the Saskatchewan Agriculture Development Fund, and the Alberta Agriculture and Food Council. S. Kirychuk has received research support from the Canadian Institutes for Health Research. V Gerdts has received research support from the Bill & Melinda Gates Foundation, the Canadian Institutes of Health Research, the National Sciences and Engineering Council (Canada), and the Alberta Agriculture Funding Consortium. D. C. Rennie has received research support from the Canadian Lung Association. D. A. Schwartz has patent rights through MedImmune. The rest of the authors have declared that they have no conflict of interest. NR 34 TC 19 Z9 19 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2009 VL 123 IS 5 BP 1034 EP 1040 DI 10.1016/j.jaci.2009.02.019 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 449CW UT WOS:000266309400008 PM 19368968 ER PT J AU Visness, CM London, SJ Daniels, JL Kaufman, JS Yeatts, KB Siega-Riz, AM Liu, AH Calatroni, A Zeldin, DC AF Visness, Cynthia M. London, Stephanie J. Daniels, Julie L. Kaufman, Jay S. Yeatts, Karin B. Siega-Riz, Anna-Maria Liu, Andrew H. Calatroni, Agustin Zeldin, Darryl C. TI Association of obesity with IgE levels and allergy symptoms in children and adolescents: Results from the National Health and Nutrition Examination Survey 2005-2006 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Atopy; allergen-specific IgE; total IgE; body mass index; obesity; overweight; allergic disease; inflammation ID BODY-MASS INDEX; ASTHMA; OVERWEIGHT; ATOPY; CONSUMPTION; PREVALENCE; FATNESS; DRINKS; ADULTS AB Background: The prevalence of both obesity and allergic disease has increased among children over the last several decades. Previous literature on the relationship between obesity and allergic disease has been inconsistent. It is not known whether systemic inflammation could be a factor in this relationship. Objective: We sought to examine the association of obesity with total and allergen-specific IgE levels and allergy symptoms in US children and adolescents and to assess the role of C-reactive protein. Methods: National Health and Nutrition Examination Survey data from 2005-2006 included measurement of total and allergen-specific IgE levels and allergy questions. Overweight was defined as the 85th or greater to less than the 95th percentile of body mass index for age, and obesity was defined as the 95th percentile or greater. Linear and logistic regression models were used to examine the association of weight categories with total IgE levels, atopy, allergen-specific IgE levels, and allergy symptoms among youth aged 2 to 19 years. Results: Geometric mean total IgE levels were higher among obese (geometric mean ratio, 1.31; 95% CI, 1.10-1.57) and overweight (ratio, 1.25; 95% CI, 1.02-1.54) children than among normal-weight children. The odds ratio (OR) for atopy (any positive specific IgE measurement) was increased in the obese children compared with that seen in those of normal weight; this association was driven largely by allergic sensitization to foods (OR for atopy, 1.26 [95% CI, 1.03-1.55]; OR for food sensitization, 1.59 [95% CI, 1.28-1.98]). C-reactive protein levels were associated with total IgE levels, atopy, and food sensitization. Conclusions: Obesity might be a contributor to the increased prevalence of allergic disease in children, particularly food allergy. Systemic inflammation might play a role in the development of allergic disease. (J Allergy Clin Immunol 2009;123:1163-9.) C1 [Visness, Cynthia M.; Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA. [Visness, Cynthia M.; Daniels, Julie L.; Kaufman, Jay S.; Yeatts, Karin B.; Siega-Riz, Anna-Maria] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [London, Stephanie J.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC USA. [Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA. [Liu, Andrew H.] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Visness, CM (reprint author), Rho Fed Syst Div Inc, 6330 Quadrangle Dr,Suite 500, Chapel Hill, NC 27517 USA. EM cindy_visness@rhoworld.com OI Kaufman, Jay/0000-0003-1606-401X; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01 ES025041-10]; National Institute of Allergy and Infections Diseases; National Institutes of Health [NO1-A1-25482] FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences(Z01 ES025041-10), and by the National Institute of Allergy and Infections Diseases, National Institutes of Health (NO1-A1-25482). NR 25 TC 66 Z9 70 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 2009 VL 123 IS 5 BP 1163 EP 1169 DI 10.1016/j.jaci.2008.12.1126 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 449CW UT WOS:000266309400027 PM 19230960 ER PT J AU Smith, ML Barnes, AJ Huestis, MA AF Smith, Michael L. Barnes, Allan J. Huestis, Marilyn A. TI Identifying New Cannabis Use with Urine Creatinine-Normalized THCCOOH Concentrations and Time Intervals Between Specimen Collections SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID EXCRETION PROFILES; 11-NOR-9-CARBOXY-DELTA(9)-TETRAHYDROCANNABINOL; MARIJUANA; RATIO; DELTA(9)-THC-COOH C1 [Barnes, Allan J.; Huestis, Marilyn A.] Natl Inst Drug Abuse, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU American Registry of Pathology; National Institutes of Health; Intramural Research Program; National Institute on Drug Abuse FX The authors thank the American Registry of Pathology and the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse for funding of this study. NR 9 TC 28 Z9 29 U1 1 U2 5 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAY PY 2009 VL 33 IS 4 BP 185 EP 189 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 440LT UT WOS:000265702500001 PM 19470219 ER PT J AU Tebas, P Zhang, J Hafner, R Tashima, K Shevitz, A Yarasheski, K Berzins, B Owens, S Forand, J Evans, S Murphy, R AF Tebas, P. Zhang, J. Hafner, R. Tashima, K. Shevitz, A. Yarasheski, K. Berzins, B. Owens, S. Forand, J. Evans, S. Murphy, R. TI Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected subjects with peripheral lipoatrophy: results of ACTG A5110 SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE nucleoside reverse transcriptase inhibitors; thymidine analogues; stavudine; zidovudine; antiretroviral treatment ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS INFECTION; MITOCHONDRIAL-DNA; HIV-1-INFECTED PATIENTS; RANDOMIZED-TRIAL; BODY-COMPOSITION; OPEN-LABEL; PROTEASE INHIBITORS; FACIAL LIPOATROPHY; TENOFOVIR DF AB Switching a thymidine analogue to a non-thymidine analogue or changing to a nucleoside-sparing regimen has been shown to partially reverse peripheral lipoatrophy. The current study evaluated both approaches. Subjects at 15 AIDS Clinical Trial Group sites receiving thymidine analogue stavudine- or zidovudine-containing regimens with plasma HIV RNA <= 500 copies/mL and lipoatrophy were prospectively randomized to: (i) switch the thymidine analogue to abacavir; (ii) discontinue all antiretrovirals and switch to lopinavir/ritonavir plus nevirapine (LPV/r+NVP); or (iii) delay switching for 24 weeks (ClinicalTrials.gov identifier: NCT00028314). Single-slice computer tomography of mid-thigh and abdominal fat and metabolic and virological/immunological parameters were measured at baseline and weeks 24 and 48. Among the 101 patients enrolled, there were significant subcutaneous thigh fat and subcutaneous abdominal tissue (SAT) increases over time and decreases in visceral adipose tissue to total adipose tissue (VAT:TAT) ratios for both interventions, and a decrease in VAT for abacavir. CD4 increased in the LPV/r+NVP arm. LPV/r+NVP had a significantly shorter time to grade 3 or higher toxicity (P = 0.007), but discontinuation rates were similar. Glucose levels did not change, but insulin decreased in the LPV/r+NVP arm. Lipids tended to increase in the LPV/r+NVP arm. Switching stavudine or zidovudine to a non-thymidine analogue or changing to a nucleoside reverse transcriptase inhibitor-sparing regimen is associated with qualitatively similar improvements in thigh fat, SAT and VAT:TAT ratio at 48 weeks. Abacavir also resulted in VAT reductions and LPV/r+NVP resulted in CD4 count increases. C1 [Tebas, P.] Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. [Zhang, J.; Evans, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hafner, R.] NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. [Tashima, K.] Brown Univ, Miriam Hosp, Ctr Immunol, Providence, RI USA. [Shevitz, A.; Forand, J.] Tufts Univ, Dept Community Hlth & Family Med, Boston, MA 02111 USA. [Yarasheski, K.] Washington Univ, Div Endocrinol Metab, St Louis, MO USA. [Berzins, B.; Murphy, R.] Northwestern Univ, Div Infect Dis, Chicago, IL 60611 USA. [Owens, S.] Frontier Sci & Technol, Amherst, NY USA. RP Tebas, P (reprint author), Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. EM pablo.tebas@uphs.upenn.edu RI Yarasheski, Kevin/A-3025-2008; OI Murphy, Robert/0000-0003-3936-2052; Yarasheski, Kevin/0000-0001-5436-2451 FU National Institute of Allergy and Infectious Disease [R21AI063995]; Abbott Laboratories Inc.; Boehringer Ingelheim, Inc. FX The study was supported by the National Institute of Allergy and Infectious Disease, R21AI063995; Abbott Laboratories Inc. and Boehringer Ingelheim, Inc. provided study medications for the study. NR 38 TC 21 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2009 VL 63 IS 5 BP 998 EP 1005 DI 10.1093/jac/dkp071 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 431XA UT WOS:000265096900023 PM 19299471 ER PT J AU Bennett, JE AF Bennett, John E. TI Management of mycoses in neutropenic patients: a brief history, 1960-2008 SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE fungi; cancer; infections ID INVASIVE FUNGAL-INFECTIONS; AMPHOTERICIN-B; ASPERGILLOSIS; THERAPY; FLUCONAZOLE; ANTIFUNGAL; CONSENSUS; DISEASE; CANCER AB The career that this symposium honours, that of Ben E. de Pauw, MD, PhD, could be said to have begun in 1970 upon his graduation from the University of Amsterdam. However, it was his move to Nijmegen in 1975 to finish his PhD studies that really began the career in which he forged expertise in haematology, oncology, immunology and infectious diseases into one spectacular career that resulted in more than 200 publications. C1 NIAID, Clin Mycol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. EM jbennett@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA FX This work was supported by the Intramural Program of the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2009 VL 63 BP I23 EP I26 DI 10.1093/jac/dkp079 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 473YH UT WOS:000268247900007 PM 19372177 ER PT J AU Lau, ST Li, H Wong, KS Zhou, QF Zhou, D Li, YC Luo, HS Shung, KK Dai, JY AF Lau, S. T. Li, H. Wong, K. S. Zhou, Q. F. Zhou, D. Li, Y. C. Luo, H. S. Shung, K. K. Dai, J. Y. TI Multiple matching scheme for broadband 0.72Pb(Mg1/3Nb2/3)O-3-0.28PbTiO(3) single crystal phased-array transducer SO JOURNAL OF APPLIED PHYSICS LA English DT Article AB Lead magnesium niobate-lead titanate single crystal 0.72Pb(Mg1/3Nb2/3)O-3-0.28PbTiO(3) (abbreviated as PMN-PT) was used to fabricate high performance ultrasonic phased-array transducer as it exhibited excellent piezoelectric properties. In this paper, we focus on the design and fabrication of a low-loss and wide-band transducer for medical imaging applications. A KLM model based simulation software PiezoCAD was used for acoustic design of the transducer including the front-face matching and backing. The calculated results show that the -6 dB transducer bandwidth can be improved significantly by using double lambda/8 matching layers and hard backing. A 4.0 MHz PMN-PT transducer array (with 16 elements) was fabricated and tested in a pulse-echo arrangement. A -6 dB bandwidth of 110% and two-way insertion loss of -46.5 dB were achieved. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3065476] C1 [Lau, S. T.; Li, H.; Wong, K. S.; Dai, J. Y.] Hong Kong Polytech Univ, Dept Appl Phys, Kowloon, Hong Kong, Peoples R China. [Zhou, Q. F.; Shung, K. K.] Univ So Calif, NIH, Ultrason Transducer Resource Ctr, Los Angeles, CA 90089 USA. [Zhou, Q. F.; Shung, K. K.] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Zhou, D.; Li, Y. C.] Shenzhen Anker High Tech Co Ltd, Shenzhen 518067, Guangdong, Peoples R China. [Luo, H. S.] Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine, Shanghai 201800, Peoples R China. RP Dai, JY (reprint author), Hong Kong Polytech Univ, Dept Appl Phys, Kowloon, Hong Kong, Peoples R China. EM apdaijy@inet.polyu.edu.hk RI Lau, Sien-Ting/B-6091-2013; Dai, Jiyan/I-7098-2013 OI Dai, Jiyan/0000-0002-7720-8032 FU Hong Kong Innovative Technology Council [K-ZP-21]; Hong Kong Polytechnic University; NIH [P41-EB2182] FX This work was supported by the Hong Kong Innovative Technology Council (Project No. K-ZP-21) and the Centre for Smart Materials of the Hong Kong Polytechnic University. The authors would like to thank Mr. Jay Williams for his help and the support from NIH Grant No. P41-EB2182. NR 15 TC 20 Z9 20 U1 2 U2 27 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-8979 J9 J APPL PHYS JI J. Appl. Phys. PD MAY 1 PY 2009 VL 105 IS 9 AR 094908 DI 10.1063/1.3065476 PG 5 WC Physics, Applied SC Physics GA 448LE UT WOS:000266263300182 PM 19657405 ER PT J AU Scahill, L Aman, MG McDougle, CJ Arnold, LE McCracken, JT Handen, B Johnson, C Dziura, J Butter, E Sukhodolsky, D Swiezy, N Mulick, J Stigler, K Bearss, K Ritz, L Wagner, A Vitiello, B AF Scahill, Lawrence Aman, Michael G. McDougle, Christopher J. Arnold, L. Eugene McCracken, James T. Handen, Benjamin Johnson, Cynthia Dziura, James Butter, Eric Sukhodolsky, Denis Swiezy, Naomi Mulick, James Stigler, Kimberly Bearss, Karen Ritz, Louise Wagner, Ann Vitiello, Benedetto TI Trial Design Challenges When Combining Medication and Parent Training in Children with Pervasive Developmental Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Clinical trial methodology; Risperidone; Behavior therapy ID ABERRANT BEHAVIOR CHECKLIST; RANDOMIZED CONTROLLED-TRIAL; ADAPTIVE-BEHAVIOR; PEDIATRIC PSYCHOPHARMACOLOGY; PSYCHOSOCIAL INTERVENTIONS; AUTISTIC-CHILDREN; CROSSOVER TRIAL; RISPERIDONE; ADOLESCENTS; PLACEBO AB This paper presents the rationale for a 24-week, randomized trial designed to test whether risperidone plus structured parent training would be superior to risperidone only on measures of noncompliance, irritability and adaptive functioning. In this model, medication reduces tantrums, aggression and self-injury; parent training promotes improvement in noncompliance and adaptive functioning. Thus, medication and parent training target related, but separate, outcomes. At week 24, the medication was gradually withdrawn to determine whether subjects in the combined treatment group could be managed on a lower dose or off medication without relapse. Both symptom reduction and functional improvement are important clinical treatment targets. Thus, experimental evidence on the beneficial effects of combining pharmacotherapy and exportable behavioral interventions is needed to guide clinical practice. C1 [Scahill, Lawrence; Dziura, James; Sukhodolsky, Denis; Bearss, Karen] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. [Aman, Michael G.; Arnold, L. Eugene; Butter, Eric; Mulick, James] Ohio State Univ, Columbus, OH 43210 USA. [McDougle, Christopher J.; Swiezy, Naomi; Stigler, Kimberly] Indiana Univ, Indianapolis, IN 46204 USA. [McCracken, James T.] Univ Calif Los Angeles, Los Angeles, CA USA. [Handen, Benjamin; Johnson, Cynthia] Univ Pittsburgh, Pittsburgh, PA USA. [Ritz, Louise; Wagner, Ann; Vitiello, Benedetto] NIMH, Rockville, MD 20857 USA. RP Scahill, L (reprint author), Yale Univ, Ctr Child Study, 230 S Frontage Rd,POB 207900, New Haven, CT 06520 USA. EM Lawrence.scahill@yale.edu OI Sukhodolsky, Denis/0000-0002-5401-792X; Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [U10 MH066768, K23 MH082119, U10MH66766, U10 MH066764, U10MH66768, K23 MH082119-02, U10 MH066766, U10MH66764] NR 38 TC 19 Z9 19 U1 2 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2009 VL 39 IS 5 BP 720 EP 729 DI 10.1007/s10803-008-0675-2 PG 10 WC Psychology, Developmental SC Psychology GA 442DP UT WOS:000265820500003 PM 19096921 ER PT J AU Casanova, MF El-Baz, A Mott, M Mannheim, G Hassan, H Fahmi, R Giedd, J Rumsey, JM Switala, AE Farag, A AF Casanova, Manuel F. El-Baz, Ayman Mott, Meghan Mannheim, Glenn Hassan, Hossam Fahmi, Rachid Giedd, Jay Rumsey, Judith M. Switala, Andrew E. Farag, Aly TI Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autistic disorder; Corpus callosum; Magnetic resonance imaging; Telencephalon ID MATTER VOLUME INCREASE; CEREBRAL-CORTEX; BRAIN SIZE; WHITE-MATTER; INFANTILE-AUTISM; GYRIFICATION; ABNORMALITIES; EVOLUTION; GROWTH; MRI AB Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients. C1 [Casanova, Manuel F.; Mott, Meghan; Switala, Andrew E.] Univ Louisville, Dept Psychiat, Louisville, KY 40292 USA. [El-Baz, Ayman] Univ Louisville, Dept Bioengn, Louisville, KY 40292 USA. [Mannheim, Glenn] US FDA, Div Psychiat Prod, Silver Spring, MD USA. [Hassan, Hossam; Fahmi, Rachid; Farag, Aly] Univ Louisville, Dept Elect & Comp Engn, Louisville, KY 40292 USA. [Giedd, Jay] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Rumsey, Judith M.] NIMH, Neurodev Disorders Branch, Bethesda, MD 20892 USA. RP Casanova, MF (reprint author), Univ Louisville, Dept Psychiat, 500 S Preston St,Bldg 55A Ste 210, Louisville, KY 40292 USA. EM manuel.casanova@louisville.edu RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; El-Baz, Ayman/0000-0001-7264-1323 FU Intramural NIH HHS [ZIA MH002794-08] NR 92 TC 41 Z9 41 U1 3 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2009 VL 39 IS 5 BP 751 EP 764 DI 10.1007/s10803-008-0681-4 PG 14 WC Psychology, Developmental SC Psychology GA 442DP UT WOS:000265820500006 PM 19148739 ER PT J AU Wallace, GL Anderson, M Happe, F AF Wallace, Gregory L. Anderson, Mike Happe, Francesca TI Brief Report: Information Processing Speed is Intact in Autism but not Correlated with Measured Intelligence SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Asperger's syndrome; Processing speed; Inspection time; Intelligence; IQ ID HIGH-FUNCTIONING AUTISM; INSPECTION TIME; SHORT FORMS; CHILDREN; ADULTS; ANNOTATION; IQ AB Speed of information processing, as measured by inspection time (IT), is a robust predictor of intellectual functioning. However, among individuals with autism and low IQ scores, IT has been reported to be discrepantly fast, and equal to that of high IQ typically developing children (Scheuffgen et al. in Dev Psychopathol 12: 83-90, 2000). The present investigation replicates and extends this study by examining IT and its relationship to IQ in a higher functioning (average range mean IQ) group of children with autism spectrum disorders (ASD) versus matched controls. Though IT was not significantly faster in the ASD group than in the matched control group, the relationship between IT and IQ was uniquely discrepant for the ASD group, partially corroborating and extending previous findings. C1 [Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Anderson, Mike] Univ Western Australia, Sch Psychol, Neurocognit Dev Unit, Perth, WA 6009, Australia. [Wallace, Gregory L.; Happe, Francesca] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England. RP Wallace, GL (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,MSN 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM gregwallace@mail.nih.gov RI Happe, Francesca/D-5544-2012; OI Happe, Francesca/0000-0001-9226-4000; Wallace, Gregory/0000-0003-0329-5054 NR 27 TC 15 Z9 15 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD MAY PY 2009 VL 39 IS 5 BP 809 EP 814 DI 10.1007/s10803-008-0684-1 PG 6 WC Psychology, Developmental SC Psychology GA 442DP UT WOS:000265820500012 PM 19148736 ER PT J AU Abreu, RD Sanchez-Diaz, PC Vogel, C Burns, SC Ko, DJ Burton, TL Vo, DT Chennasamudaram, S Le, SY Shapiro, BA Penalva, LOF AF Abreu, Raquel de Sousa Sanchez-Diaz, Patricia C. Vogel, Christine Burns, Suzanne C. Ko, Daijin Burton, Tarea L. Vo, Dat T. Chennasamudaram, Soudhamini Le, Shu-Yun Shapiro, Bruce A. Penalva, Luiz O. F. TI Genomic Analyses of Musashi1 Downstream Targets Show a Strong Association with Cancer-related Processes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-BINDING PROTEIN; ARF TUMOR-SUPPRESSOR; MESSENGER-RNA; STEM-CELLS; RIBONUCLEOPROTEIN COMPLEXES; POSTTRANSCRIPTIONAL OPERONS; STATISTICAL-MODEL; GENE-EXPRESSION; P53; MDM2 AB Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal functions in stem cell maintenance, nervous system development, and tumorigenesis. Despite its importance, only three direct mRNA targets have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has been shown to affect their translation by binding to short elements located in the 3'-untranslated region. To better understand Msi1 functions, we initially performed an RIP-Chip analysis in HEK293T cells; this method consists of isolation of specific RNA-protein complexes followed by identification of the RNA component via microarrays. A group of 64 mRNAs was found to be enriched in the Msi1-associated population compared with controls. These genes belong to two main functional categories pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell differentiation, and apoptosis and 2) protein modification (including ubiquitination and ubiquitin cycle). To corroborate our findings, we examined the impact of Msi1 expression on both mRNA (transcriptomic) and protein (proteomic) expression levels. Genes whose mRNA levels were affected by Msi1 expression have a Gene Ontology distribution similar to RIP-Chip results, reinforcing Msi1 participation in cancer-related processes. The proteomics study revealed that Msi1 can have either positive or negative effects on gene expression of its direct targets. In summary, our results indicate that Msi1 affects a network of genes and could function as a master regulator during development and tumor formation. C1 [Burton, Tarea L.; Vo, Dat T.; Chennasamudaram, Soudhamini; Penalva, Luiz O. F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Vogel, Christine] Univ Texas Austin, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Ko, Daijin] Univ Texas San Antonio, Dept Management Sci & Stat, San Antonio, TX 78229 USA. [Le, Shu-Yun; Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Computat RNA Struct Grp, NIH, Frederick, MD 21702 USA. RP Penalva, LOF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Childrens Canc Res Inst, Mail Code 7784,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM penalva@uthscsa.edu FU National Institutes of Health Intramural Research Program; NCI; Center for Cancer Research; San Antonio Area Foundation [PGID122760]; San Antonio Cancer Institute; American Cancer Society [PGID 124139]; Tengg Foundation [PGID 127793]; International Human Frontier Science Program FX Supported by the International Human Frontier Science Program. NR 48 TC 38 Z9 40 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 2009 VL 284 IS 18 BP 12125 EP 12135 DI 10.1074/jbc.M809605200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437NQ UT WOS:000265494600044 ER PT J AU Tamura, T Smith, M Kanno, T Dasenbrock, H Nishiyama, A Ozato, K AF Tamura, Tomohiko Smith, Matthew Kanno, Tomohiko Dasenbrock, Hormuzdiyer Nishiyama, Akira Ozato, Keiko TI Inducible Deposition of the Histone Variant H3.3 in Interferon-stimulated Genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVE GENES; EPIGENETIC INHERITANCE; GENOME-WIDE; CHROMATIN; TRANSCRIPTION; METHYLATION; PROMOTERS; CELLS; MARKS; RNA AB The H3.3 histone variant is synthesized throughout cell cycle and deposited onto chromatin in a replication-independent manner. It is enriched in transcriptionally active regions of chromatin and is implicated in epigenetic memory. The dynamics of H3.3 deposition during transcriptional activation, however, have not been fully studied so far. Here we examined H3.3 incorporation into interferon (IFN)-stimulated genes in confluent mouse NIH3T3 cells expressing H3.3 fused to the yellow fluorescent protein (YFP). Following IFN stimulation, H3.3-YFP was rapidly incorporated into all four IFN-activated genes tested, with the highest enrichment seen in the distal end of the coding region. Surprisingly, H3.3 enrichment in the coding region continued for an extended period of time, long after transcription ceased. The promoter region, although constitutively enriched with H3.3-YFP, did not show an increase in its deposition in response to IFN stimulation. Further, although H3.3-YFP deposition stably remained in non-dividing cells for days after IFN stimulation, it was rapidly diminished in dividing cells. Lastly, we examined the role of H3.3 in IFN-stimulated transcription by a short hairpin RNA approach and found that IFN-stimulated transcription was significantly impaired in H3.3 knockdown cells. Results indicate that H3.3 plays a role in IFN-mediated transcription, and its deposition leaves a prolonged post-transcriptional mark in these genes. C1 [Tamura, Tomohiko; Smith, Matthew; Kanno, Tomohiko; Dasenbrock, Hormuzdiyer; Nishiyama, Akira; Ozato, Keiko] Eunice Kennedy Shriver NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Ozato, K (reprint author), NICHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01,6 Ctr Dr,MSC 2753, Bethesda, MD 20892 USA. EM ozatok@mail.nih.gov OI Smith, Matthew/0000-0001-6614-569X FU National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grant through the Intramural Research Program of Eunice Kennedy Shriver NICHD. NR 42 TC 34 Z9 34 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 2009 VL 284 IS 18 BP 12217 EP 12225 DI 10.1074/jbc.M805651200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437NQ UT WOS:000265494600053 PM 19244243 ER PT J AU Lin, HM Lee, JH Yadav, H Kamaraju, AK Liu, E Duan, ZG Vieira, A Kim, SJ Collins, H Matschinsky, F Harlan, DM Roberts, AB Rane, SG AF Lin, Huei-Min Lee, Ji-Hyeon Yadav, Hariom Kamaraju, Anil K. Liu, Eric Duan Zhigang Vieira, Anthony Kim, Seong-Jin Collins, Heather Matschinsky, Franz Harlan, David M. Roberts, Anita B. Rane, Sushil G. TI Transforming Growth Factor-beta/Smad3 Signaling Regulates Insulin Gene Transcription and Pancreatic Islet beta-Cell Function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMAD BINDING-ELEMENT; TGF-BETA; TARGETED DISRUPTION; EXOCRINE PANCREAS; RECEPTOR; SECRETION; PROMOTER; REPRESSION; EXPRESSION; ACTIVIN AB Pancreatic islet beta-cell dysfunction is a signature feature of Type 2 diabetes pathogenesis. Consequently, knowledge of signals that regulate beta-cell function is of immense clinical relevance. Transforming growth factor (TGF)-beta signaling plays a critical role in pancreatic development although the role of this pathway in the adult pancreas is obscure. Here, we define an important role of the TGF-beta pathway in regulation of insulin gene transcription and beta-cell function. We identify insulin as a TGF-beta target gene and show that the TGF-beta signaling effector Smad3 occupies the insulin gene promoter and represses insulin gene transcription. In contrast, Smad3 small interfering RNAs relieve insulin transcriptional repression and enhance insulin levels. Transduction of adenoviral Smad3 into primary human and non-human primate islets suppresses insulin content, whereas, dominant-negative Smad3 enhances insulin levels. Consistent with this, Smad3-deficient mice exhibit moderate hyperinsulinemia and mild hypoglycemia. Moreover, Smad3 deficiency results in improved glucose tolerance and enhanced glucose-stimulated insulin secretion in vivo. In ex vivo perifusion assays, Smad3-deficient islets exhibit improved glucose-stimulated insulin release. Interestingly, Smad3-deficient islets harbor an activated insulin-receptor signaling pathway and TGF-beta signaling regulates expression of genes involved in beta-cell function. Together, these studies emphasize TGF-beta/Smad3 signaling as an important regulator of insulin gene transcription and beta-cell function and suggest that components of the TGF-beta signaling pathway may be dysregulated in diabetes. C1 [Lin, Huei-Min; Lee, Ji-Hyeon; Yadav, Hariom; Kamaraju, Anil K.; Liu, Eric; Duan Zhigang; Harlan, David M.; Rane, Sushil G.] NIDDK, Diabet Branch, Bethesda, MD 20892 USA. [Vieira, Anthony; Roberts, Anita B.] NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. [Kim, Seong-Jin] Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Songdo 406840, Incheon, South Korea. [Collins, Heather; Matschinsky, Franz] Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Rane, SG (reprint author), CRC, 5-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM ranes@mail.nih.gov OI Yadav, Hariom/0000-0003-4504-1597 FU National Institutes of Health Intramural Program FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Program. NR 54 TC 65 Z9 67 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 2009 VL 284 IS 18 BP 12246 EP 12257 DI 10.1074/jbc.M805379200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437NQ UT WOS:000265494600056 PM 19265200 ER PT J AU Jackson-Rosario, S Cowart, D Myers, A Tarrien, R Levine, R Scott, R Self, W AF Jackson-Rosario, Sarah Cowart, Darin Myers, Andrew Tarrien, Rebecca Levine, Rodney L. Scott, Robert A. Self, William Thomas TI Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au-Se adduct SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE Auranofin; Selenium; Extended X-ray absorption fine structure; Clostridium difficile; Antimicrobial ID ANAEROBES GENUS CLOSTRIDIUM; ESCHERICHIA-COLI; GLYCINE REDUCTASE; SELENOCYSTEINE SYNTHASE; THIOREDOXIN REDUCTASE; LIQUID-CHROMATOGRAPHY; TRIFLUOROACETIC-ACID; PROLINE REDUCTION; GOLD COMPLEXES; CL.-SPOROGENES AB Clostridium difficile is a nosocomial pathogen whose incidence and importance are on the rise. Previous work in our laboratory characterized the central role of selenoenzyme-dependent Stickland reactions in C. difficile metabolism. In this work we have identified, using mass spectrometry, a stable complex formed upon reaction of auranofin (a gold-containing drug) with selenide in vitro. X-ray absorption spectroscopy supports the structure that we proposed on the basis of mass-spectrometric data. Auranofin potently inhibits the growth of C. difficile but does not similarly affect other clostridia that do not utilize selenoproteins to obtain energy. Moreover, auranofin inhibits the incorporation of radioisotope selenium (Se-75) in selenoproteins in both Escherichia coli, the prokaryotic model for selenoprotein synthesis, and C. difficile without impacting total protein synthesis. Auranofin blocks the uptake of selenium and results in the accumulation of the auranofin-selenide adduct in the culture medium. Addition of selenium in the form of selenite or L-selenocysteine to the growth medium significantly reduces the inhibitory action of auranofin on the growth of C. difficile. On the basis of these results, we propose that formation of this complex and the subsequent deficiency in available selenium for selenoprotein synthesis is the mechanism by which auranofin inhibits C. difficile growth. This study demonstrates that targeting selenium metabolism provides a new avenue for antimicrobial development against C. difficile and other selenium-dependent pathogens. C1 [Jackson-Rosario, Sarah; Myers, Andrew; Tarrien, Rebecca; Self, William Thomas] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Orlando, FL 32816 USA. [Cowart, Darin; Scott, Robert A.] Univ Georgia, Dept Chem & Biochem, Athens, GA 30602 USA. [Cowart, Darin; Scott, Robert A.] Univ Georgia, Dept Mol Biol, Athens, GA 30602 USA. [Levine, Rodney L.] NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Self, W (reprint author), Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, 4000 Cent Florida Blvd,Bldg 20,Room 124, Orlando, FL 32816 USA. EM wself@mail.ucf.edu RI Self, William/A-6704-2008 FU National Institutes of Health [GM042025, ES01434]; Department of Energy; Office of Biological and Environmental Research; National Center for Research Resources; Biomedical Technology Program; Florida Department of Health [05-NIR-10] FX The authors thank Michel Warny (Acambis, Cambridge, MA, USA) for providing C. difficile NAPI/027. We also thank August Bock (University of Munich, Munich, Germany) for providing E. coli strain WL400 (selD). The Au compounds used as models were generous gifts from Susan Miller, University of California San Francisco. XAS work in the Scott group is supported by a grant from the National Institutes of Health (GM042025). Portions of this research were carried out at the Stanford Synchrotron Radiation Laboratory, a national user facility operated by Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences. The Stanford Synchrotron Radiation Laboratory Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research, and by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program. This work was supported in part by the Intramural Research Program of the National Institutes of Health (NHLBI). This work was also supported in part by grants to W. T. S. from the Florida Department of Health (05-NIR-10) and the National Institutes of Health (ES01434). NR 50 TC 28 Z9 29 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0949-8257 EI 1432-1327 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD MAY PY 2009 VL 14 IS 4 BP 507 EP 519 DI 10.1007/s00775-009-0466-z PG 13 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 436FJ UT WOS:000265397800003 PM 19165513 ER PT J AU Sarkar, P Koushik, SV Vogel, SS Gryczynski, I Gryczynski, Z AF Sarkar, Pabak Koushik, Srinagesh V. Vogel, Steven S. Gryczynski, Ignacy Gryczynski, Zygmunt TI Photophysical properties of Cerulean and Venus fluorescent proteins SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Forster resonance energy transfer; fluorescence timeline; fluorescence anisotropy ID LIVING CELLS; GFP; FRET; MICROSCOPY; VISUALIZATION; MATURATION; DYNAMICS; VARIANT; PROBES; RFLIM AB Cerulean and Venus are recently developed fluorescent proteins, often used as a donor-acceptor pair by researchers in Forster resonance energy transfer-based colocalization studies. We characterized the fluorescent properties of these two proteins in a broad spectral range (form ultraviolet to visible region). Excitation spectra, lifetimes, and polarization spectra show significant energy transfer from aromatic amino acids to the fluorescent protein chromophore. High steady-state anisotropy values and the lack of a fast component in anisotropy decays show that the fluorescent protein chromophore is rigidly fixed within the protein structure. Furthermore, we show that the chromophores are not accessible to external quenchers, such as acrylamide or potassium iodide (KI), allowing the removal of "unwanted" background in the environment with external quencher, while leaving the Cerulean/Venus fluorescence unchanged. (C) 2009 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3156842] C1 [Sarkar, Pabak; Gryczynski, Zygmunt] Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA. [Sarkar, Pabak; Gryczynski, Ignacy; Gryczynski, Zygmunt] Univ N Texas, Hlth Sci Ctr, Ctr Commercializat Fluorescent Technol, Ft Worth, TX 76107 USA. [Gryczynski, Ignacy] Univ N Texas, Hlth Sci Ctr, Dept Cell Biol & Genet, Ft Worth, TX 76107 USA. [Koushik, Srinagesh V.; Vogel, Steven S.] NIAAA, NIH, Lab Mol Physiol, Bethesda, MD 20892 USA. RP Gryczynski, Z (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA. EM zgryczyn@hsc.unt.edu RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 FU National Institutes of Health [ZO1AA000452-01]; Texas Emerging Technologies Fund FX This research was supported by the National Institutes of Health Project No. ZO1AA000452-01 to S. S. V., and by the Texas Emerging Technologies Fund Grant to Z. G. NR 33 TC 21 Z9 21 U1 1 U2 15 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2009 VL 14 IS 3 AR 034047 DI 10.1117/1.3156842 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 477RN UT WOS:000268536300055 PM 19566339 ER PT J AU Mueller, GA AF Mueller, Geoffrey A. TI Analytical solution to the coupled evolution of multidimensional NMR data SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE NMR; Coevolution; Multi-way decomposition; Projection reconstruction ID MULTIWAY DECOMPOSITION; 3-WAY DECOMPOSITION; PROJECTION-RECONSTRUCTION; REDUCED DIMENSIONALITY; PROTEIN BACKBONE; SPECTRA; RESONANCE; ASSIGNMENT; PERIODS; IDENTIFICATION AB A substantial time savings in the collection of multidimensional NMR data can be achieved by coupling the evolution of nuclei in the indirect dimensions. In order to save time, the sampling of the indirect dimensions is inherently incomplete. Therefore, many algorithms and samplings schemes have been developed aimed at separating the coevolved frequencies into analyzable data with limited artifacts. This paper extends the use of circulant matrices to describe coupled evolution with convolutions. By understanding the data in terms of convolutions, there is an exact solution to the inversion problem of extracting the orthogonal vectors from the coupled dimensions. Previously, this inversion problem has been solved using peak coordinates extracted from spectra. In contrast, the method described here uses spectra directly. This solution suggests a simple sampling scheme of collecting N orthogonal spectra, and N + 1 projections at specific projection angles, however, the theory developed can be extended generally to arbitrary projection angles. The circulant matrix methodology is demonstrated for simulated and real data. Further, an algorithm for separating overlapped signals in the detected dimension is presented. The algorithm involves the forward calculation of the coupled spectra from the orthogonal spectra, followed by back calculation of the orthogonal spectra from the coupled spectra, thus permitting rigorous cross-validation. This algorithm is shown to be robust in that erroneous solutions give rise to large artifacts. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Mueller, GA (reprint author), NIEHS, 111 TW Alexander Dr,MD MR 01, Res Triangle Pk, NC 27709 USA. EM Mueller3@niehs.nih.gov FU Intramural Program of the NIH; National Institute of Environmental Health Sciences FX The author wishes to thank Brian Coggins and Ron Venters for many useful discussions and a critical reading of the manuscript. Additionally stimulating were discussions with Martin Billeter, Eugene DeRose, and Robert London. This research was supported by the Intramural Program of the NIH, National Institute of Environmental Health Sciences. NR 25 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAY PY 2009 VL 44 IS 1 BP 13 EP 23 DI 10.1007/s10858-009-9309-z PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 437ZB UT WOS:000265524300002 PM 19308330 ER PT J AU Uveges, TE Kozloff, KM Ty, JM Ledgard, F Raggio, CL Gronowicz, G Goldstein, SA Marini, JC AF Uveges, Thomas E. Kozloff, Kenneth M. Ty, Jennifer M. Ledgard, Felicia Raggio, Cathleen L. Gronowicz, Gloria Goldstein, Steven A. Marini, Joan C. TI Alendronate Treatment of the Brtl Osteogenesis Imperfecta Mouse Improves Femoral Geometry and Load Response Before Fracture but Decreases Predicted Material Properties and Has Detrimental Effects on Osteoblasts and Bone Formation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Brtl mouse; bisphosphonates; osteogenesis imperfecta; biomechanics; histomorphometry; bone quality ID INTRAVENOUS PAMIDRONATE TREATMENT; CHILDREN; MODEL; BISPHOSPHONATES; THERAPY; INFANTS; TISSUE; MICE; IV; MINERALIZATION AB Long courses of bisphosphonates are widely administered to children with osteogenesis imperfecta (Of), although bisphosphonates do not block mutant collagen secretion and may affect bone matrix composition or structure. The Brtl mouse has a glycine substitution in colla1 and is ideal for modeling the effects of bisphosphonate in classical OI. We treated Brtl and wildtype mice with alendronate (Aln; 0.219 mg/kg/wk, SC) for 6 or 12 wk and compared treated and untreated femora of both genotypes. Mutant and wildtype bone had similar responses to Aln treatment. Femoral areal BMD and cortical volumetric BMD increased significantly after 12 wk, but femoral length and growth curves were unaltered. Aln improved Brtl diaphyseal cortical thickness and trabecular number after 6 wk and cross-sectional shape after 12 wk. Mechanically, Aln significantly increased stiffness in wildtype femora and load to fracture in both genotypes after 12 wk. However, predicted material strength and elastic modulus were negatively impacted by 12 wk of Aln in both genotypes, and metaphyseal remnants of mineralized cartilage also increased. Brtl femoral brittleness was unimproved. Brtl osteoclast and osteoblast surface were unchanged by treatment. However, decreased mineral apposition rate and bone formation rate/bone surface and the flattened morphology of Brtl osteoblasts suggested that Aln impaired osteoblast function and matrix synthesis. We conclude that Aln treatment improves Brtl femoral geometry and load to fracture but decreases bone matrix synthesis and predicted material modulus and strength, with striking retention of mineralized cartilage. Beneficial and detrimental changes appear concomitantly. Limiting cumulative bisphosphonate exposure of 01 bone will minimize detrimental effects. C1 [Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Kozloff, Kenneth M.; Goldstein, Steven A.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. [Ledgard, Felicia; Gronowicz, Gloria] Univ Connecticut, Ctr Hlth, Dept Surg, Farmington, CT USA. [Raggio, Cathleen L.] Hosp Special Surg, Ctr Skeletal Dysplasias, New York, NY 10021 USA. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 10,Room 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov OI Gronowicz, Gloria/0000-0001-7158-3598 FU NICHD; NIH [AR46024]; The Center for Histology and Histomorphometry at the University of Connecticut FX The authors thank Aileen Barnes, NIS (BEMB, NICHD), for assistance with the microscopy and photography of bone sections for Fig. 5. This work was supported by NICHD Intramural Funding (J.C.M.), NIH AR46024 (S.G.), and The Center for Histology and Histomorphometry at the University of Connecticut (G.A.G.). NR 42 TC 37 Z9 37 U1 1 U2 9 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2009 VL 24 IS 5 BP 849 EP 859 DI 10.1359/JBMR.081238 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 438IV UT WOS:000265550000012 PM 19113917 ER PT J AU Theman, TA Collins, MT Dempster, DW Zhou, H ReynoldS, JC Brahim, JS Roschger, P Klaushofer, K Winer, KK AF Theman, Todd A. Collins, Michael T. Dempster, David W. Zhou, Hua ReynoldS, James C. Brahim, Jaime S. Roschger, Paul Klaushofer, Klaus Winer, Karen K. TI PTH(1-34) Replacement Therapy in a Child With Hypoparathyroidism Caused by a Sporadic Calcium Receptor Mutation SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE calcium-sensing receptor; PTH; histomorphometry; quantitative backscattered electron imaging; BMD distribution ID PARATHYROID-HORMONE 1-34; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; CA2+-SENSING RECEPTOR; SENSING RECEPTOR; LUMBAR SPINE; OSTEOPOROSIS; RATS; TERIPARATIDE; MONKEYS AB Autosomal dominant hypocalcemia (ADH) is an inherited form of hypoparathyroidism caused by activating mutations in the calcium-sensing receptor (CaR). Treatment with PTH(1-34) may be superior to conventional therapy but is contraindicated in children, and long-term effects on the skeleton are unknown. The patient is a 20-yr-old female with ADH treated with PTH continuously since 6 yr and 2 mo of age. A bone biopsy was obtained for histomorphometry and quantitative backscattered electron imaging (qBEI). Her data were compared with one age-, sex-, and length of hypoparathyroidism-matched control not on PTH and two sex-matched ADH controls before and after 1 yr of PTH. The patient's growth was normal. Hypercalciuria and hypermagnesuria persisted despite normal or subnormal serum calcium and magnesium levels. Nephrocalcinosis, without evidence of impaired renal function, developed by 19 yr of age. Cancellous bone volume was dramatically elevated in the patient and in ADH controls after 1 yr of PTH. BMD distribution (BMDD) by qBEI of the patient and ADH controls was strikingly shifted toward lower mineralization compared with the non-ADH control. Moreover, the ADH controls exhibited a further reduction in mineralization after I yr of PTH. These findings imply a role for CaR in bone matrix mineralization. There were no fractures or osteosarcoma. In conclusion, long-term PTH replacement in a child with ADH was not unsafe, increased bone mass without negatively impacting mineralization, and improved serum mineral control but did not prevent nephrocalcinosis. Additionally, this may be the first evidence of a role for CaR in human bone. C1 [Collins, Michael T.] NIDCR, Skeletal Clin Studies Unit, CSDB, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. [Dempster, David W.; Zhou, Hua] Helen Hayes Hosp, Reg Bone Ctr, New York, NY USA. [ReynoldS, James C.] NIH, Dept Nucl Med, Dept Hlth & Human Serv, Bethesda, MD USA. [Brahim, Jaime S.] NIH, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Roschger, Paul; Klaushofer, Klaus] Hanusch Hosp WGKK, Ludwig Boltzmann Inst Osteol, Vienna, Austria. [Roschger, Paul; Klaushofer, Klaus] Hanusch Hosp, AUVA Trauma Ctr Meidling, Dept Med 4, Vienna, Austria. [Winer, Karen K.] NICHHD, Endocrinol Nutr & Growth Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Collins, MT (reprint author), NIDCR, Skeletal Clin Studies Unit, CSDB, Dept Hlth & Human Serv,NIH, 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. EM mc247k@nih.gov FU DIR, NIDCR; DIR, NICHD; IRP, NIH, DHHS; Pfizer; AUVA (Austrian Social Insurance for Occupational Risk); WGKK (Social Health Insurance Vienna); FWF (Austrian Science Fund) [P19009-N20] FX We are indebted to the patient and her family for participation and to Marilyn Kelly for coordinating. This research was supported in part by the DIR, NIDCR and the DIR, NICHD, of the IRP, NIH, DHHS. T.A.T. was supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer (through a grant to the Foundation for NIH from Pfizer). P.R. and K.K. were supported by AUVA (Austrian Social Insurance for Occupational Risk), WGKK (Social Health Insurance Vienna), and FWF (Austrian Science Fund) Project P19009-N20. NR 44 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 2009 VL 24 IS 5 BP 964 EP 973 DI 10.1359/JBMR.081233 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 438IV UT WOS:000265550000022 PM 19063686 ER PT J AU Cirillo, P Giallauria, F Pacileo, M Petrillo, G D'Agostino, M Vigorito, C Chiariello, M AF Cirillo, Plinio Giallauria, Francesco Pacileo, Mario Petrillo, Gianluca D'Agostino, Mariantonietta Vigorito, Carlo Chiariello, Massimo TI Increased High Mobility Group Box-1 Protein Levels are Associated With Impaired Cardiopulmonary and Echocardiographic Findings After Acute Myocardial Infarction SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE High mobility group box-1 protein; heart failure; post infarction; inflammation ID CHRONIC HEART-FAILURE; HIGH-MOBILITY-GROUP-BOX-1 PROTEIN; CARDIAC REHABILITATION; CLINICAL-IMPLICATIONS; CYTOKINE; CELLS; HMGB1; INFLAMMATION; PROGNOSIS; MORTALITY AB Background: Several markers of systemic inflammation seem to play an active role in the pathophysiology of acute coronary syndrome and its evolution. High mobility group box-1 (HMGB-1), a ubiquitous nuclear protein constitutively expressed in quiescent cells, was recently recognized as a newer critical mediator of inflammatory diseases. The present study aimed to evaluate the possible association between HMGB-1 levels and structural and functional indices of cardiovascular performance such as cardiopulmonary and Doppler-echocardiography indices in patients after acute myocardial infarction (MI). Methods and Results: Fifty-four consecutive patients (mean age 58.3 years, 83% males) recovering from acute MI were included in the study protocol. All patients underwent Doppler-echocardiography, cardiopulmonary exercise, and HMGB-1 assay. HMGB-1 levels in acute MI patients were significantly higher compared with age- and body mass index-matched controls (14.8 +/- 6.8 vs. 2.3 +/- 1.0 ng/mL, P < .0001, respectively). Postinfarction patients showed oxygen consumption at peak exercise (VO(2peak)) = 14.4 +/- 4.2 mL.kg.min and a slope of increase in ventilation over carbon dioxide output (VE/VCO(2slope)) = 32.1 +/- 6.2, whereas Doppler-echocardiography values were: left ventricular end-diastolic volume (LVEDV) = 53.4 +/- 8.2 mL/m(2); left ventricular ejection fraction (LVEF) = 41.7 +/- 7.0%. Multiple linear regression analysis (stepwise method) showed that VO(2peak) (beta = -0.276, P = .012), VE/VCO(2slope) (beta = 0.244, P = .005), LVEDV (beta = 0.267, P = .018), peak creatine kmase-MB (beta = 0.339, P = .004), peak Troponin I (beta = 0.244, P = .002), and LVEF (beta = -0.312, P = .021) were significantly associated with HMGB-1 levels. Conclusions: The present study demonstrated that in postinfarction patients, HMGB-1 levels were significantly higher compared with controls, and significantly correlated with cardiopulmonary and Doppler-echocardiography parameters. (J Cardiac Fail 2009;15:362-367) C1 [Cirillo, Plinio; Pacileo, Mario; Petrillo, Gianluca; Chiariello, Massimo] Univ Naples Federico 2, Div Cardiol, I-80131 Naples, Italy. [Giallauria, Francesco; D'Agostino, Mariantonietta; Vigorito, Carlo] Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med Cardiovasc & Immunol Sci, I-80131 Naples, Italy. [Giallauria, Francesco] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Cirillo, P (reprint author), Univ Naples Federico 2, Div Cardiol, Via Sergio Pansini 5, I-80131 Naples, Italy. EM pcirillo@unina.it RI Giallauria, Francesco/B-5681-2013; OI Giallauria, Francesco/0000-0003-4119-9397; CIRILLO, Plinio/0000-0001-7818-4952 NR 38 TC 16 Z9 17 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD MAY PY 2009 VL 15 IS 4 BP 362 EP 367 DI 10.1016/j.cardfail.2008.11.010 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 444DG UT WOS:000265960000013 PM 19398086 ER PT J AU Kostova, Z Mariano, J Scholz, S Koenig, C Weissman, AM AF Kostova, Zlatka Mariano, Jennifer Scholz, Simone Koenig, Carolin Weissman, Allan M. TI A Ubc7p-binding domain in Cue1p activates ER-associated protein degradation SO JOURNAL OF CELL SCIENCE LA English DT Article DE ER-associated degradation; Proteasome; Ubiquitin; S. cerevisiae; CUE1; UBC7 ID RETICULUM-ASSOCIATED DEGRADATION; UBIQUITIN LIGASE GP78; ENDOPLASMIC-RETICULUM; SACCHAROMYCES-CEREVISIAE; LUMINAL PROTEIN; IN-VIVO; RECOGNITION; PATHWAY; INSIG-1; REVEALS AB Cue1p is an N-terminally anchored endoplasmic reticulum (ER) protein essential for the activity of the two major yeast RING finger ubiquitin ligases (E3s) implicated in ER-associated degradation (ERAD). Cue1p contains a CUE domain, which for several proteins is known to bind ubiquitin. We now establish that the CUE domain is dispensable for ERAD of substrates of both Hrd1p and Doa10p and that the Cue1p transmembrane domain is similarly not required for degradation of the Hrd1p substrate CPY*. Cue1p interacts with the ERAD E2 Ubc7p in vivo. We show that a discrete C-terminal Ubc7p binding region (U7BR) of Cue1p is required for ERAD and for Ubc7p-dependent ubiquitylation by Hrd1p in vitro. Strikingly, when Ubc7p is stabilized by direct anchoring to the ER membrane, the U7BR is sufficient to restore ERAD in cells lacking Cue1p. Thus, discrete E2 binding sites independent of ubiquitin ligase domains have the potential to activate ubiquitylation. C1 [Kostova, Zlatka; Mariano, Jennifer; Scholz, Simone; Koenig, Carolin; Weissman, Allan M.] NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. EM amw@nih.gov FU Intramural NIH HHS NR 30 TC 23 Z9 23 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2009 VL 122 IS 9 BP 1374 EP 1381 DI 10.1242/jcs.044255 PG 8 WC Cell Biology SC Cell Biology GA 436VD UT WOS:000265443300013 PM 19366730 ER PT J AU Zhang, T Zaal, KJM Sheridan, J Mehta, A Gundersen, GG Ralston, E AF Zhang, Tan Zaal, Kristien J. M. Sheridan, John Mehta, Amisha Gundersen, Gregg G. Ralston, Evelyn TI Microtubule plus-end binding protein EB1 is necessary for muscle cell differentiation, elongation and fusion SO JOURNAL OF CELL SCIENCE LA English DT Article DE EB1; Microtubules; Skeletal muscle differentiation ID MYOGENIC DIFFERENTIATION; BETA-CATENIN; MIGRATING FIBROBLASTS; TRACKING PROTEINS; GOLGI-COMPLEX; IN-VITRO; DYNAMICS; STABILITY; STABILIZATION; INTERACTS AB During muscle differentiation, microtubule stability, nucleation and orientation all undergo profound changes, which are simultaneous with and possibly necessary for the elongation and fusion of muscle cells. We do not yet understand these events, but they present similarities with the polarized migration of fibroblasts, in which EB1 is necessary for microtubule stabilization. However, it was recently reported that EB3, not EB1, is involved in muscle cell elongation and fusion, and that neither of these two proteins influences microtubule stabilization. To re-examine the role of EB1, we have generated C2 cell lines permanently expressing EB1-targeted shRNAs. In these lines, EB1 is specifically knocked down by more than 90% before any differentiation-related changes can take place. We find that differentiation (assessed by myogenin expression), elongation and fusion are prevented. In addition, two early events that normally precede differentiation - microtubule stabilization and the accumulation of cadherin and beta-catenin on the plasma membrane - are inhibited. Re-expression of EB1 as EB1-GFP restores all aspects of normal differentiation, whereas overexpression of EB3-GFP restores elongation but not fusion. We conclude that EB1 is necessary for the early stages of muscle differentiation. C1 [Zhang, Tan; Zaal, Kristien J. M.; Sheridan, John; Mehta, Amisha; Ralston, Evelyn] NIAMSD, Light Imaging Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Gundersen, Gregg G.] Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA. RP Zhang, T (reprint author), NIAMSD, Light Imaging Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. EM zhangt1@mail.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM062939] NR 49 TC 34 Z9 37 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2009 VL 122 IS 9 BP 1401 EP 1409 DI 10.1242/jcs.039255 PG 9 WC Cell Biology SC Cell Biology GA 436VD UT WOS:000265443300016 PM 19366726 ER PT J AU Barski, A Zhao, K AF Barski, Artem Zhao, Keji TI Genomic Location Analysis by ChIP-Seq SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ChIP-Seq; CHROMATIN; TRANSCRIPTION FACTOR ID FACTOR-BINDING-SITES; CHROMATIN IMMUNOPRECIPITATION; TRANSCRIPTION FACTORS; DNA INTERACTIONS; SERIAL ANALYSIS; WIDE ANALYSIS; STEM-CELLS; T-CELLS; IDENTIFICATION; PROMOTERS AB The interaction of a multitude of transcription factors and other chromatin proteins with the genome can influence gene expression and subsequently cell differentiation and function. Thus systematic identification of binding targets of transcription factors is key to unraveling gene regulation networks. The recent development of ChIP-Seq has revolutionized mapping of DNA-protein interactions. Now protein binding can be mapped in a truly genome-wide manner with extremely high resolution. This review discusses ChIP-Seq technology, its possible pitfalls, data analysis and several early applications. J. Cell. Biochem. 107: 11-18, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Barski, Artem; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Barski, A (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM barskia@nhlbi.nih.gov; zhaok@nhlbi.nih.gov OI Barski, Artem/0000-0002-1861-5316 FU H; National Heart, Lung and Blood Institute FX Grant sponsor: Intramural Research Program of the NIH; Grant: sponsor: National Heart, Lung and Blood Institute. NR 65 TC 98 Z9 99 U1 2 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAY 1 PY 2009 VL 107 IS 1 BP 11 EP 18 DI 10.1002/jcb.22077 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 440OR UT WOS:000265710100003 PM 19173299 ER PT J AU Bishu, S Schmidt, KC Burlin, TV Channing, MA Horowitz, L Huang, TJ Liu, ZH Qin, M Vuong, BK Unterman, AJ Xia, ZY Zametkin, A Herscovitch, P Quezado, Z Smith, CB AF Bishu, Shrinivas Schmidt, Kathleen C. Burlin, Thomas V. Channing, Michael A. Horowitz, Lisa Huang, Tianjiang Liu, Zhong-hua Qin, Mei Vuong, B-K Unterman, Aaron J. Xia, Zengyan Zametkin, Alan Herscovitch, Peter Quezado, Zenaide Smith, Carolyn B. TI Propofol anesthesia does not alter regional rates of cerebral protein synthesis measured with L-[1-(11)C]leucine and PET in healthy male subjects SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE anesthesia; brain; human; propofol; protein synthesis; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; AMINO-ACIDS; KINETIC-MODELS; RHESUS-MONKEYS; NORMAL VALUES; BLOOD-FLOW; BRAIN; METABOLISM; TISSUE AB We report regional rates of cerebral protein synthesis (rCPS) in 10 healthy young males, each studied under two conditions: awake and anesthetized with propofol. We used the quantitative L-[1-(11)C] leucine positron emission tomography (PET) method to measure rCPS. The method accounts for the fraction (lambda) of unlabeled leucine in the precursor pool for protein synthesis that is derived from arterial plasma; the remainder comes from proteolysis of tissue proteins. Across 18 regions and whole brain, mean differences in rCPS between studies ranged from-5% to 5% and were within the variability of rCPS in awake studies (coefficient of variation range: 7% to 14%). Similarly, differences in lambda (range: 1% to 4%) were typically within the variability of lambda (coefficient of variation range: 3% to 6%). Intersubject variances and patterns of regional variation were also similar under both conditions. In propofol-anesthetized subjects, rCPS varied regionally from 0.98 +/- 0.12 to 2.39 +/- 0.23 nmol g(-1) min(-1) in the corona radiata and in the cerebellum, respectively. Our data indicate that the values, variances, and patterns of regional variation in rCPS and lambda measured by the L-[1-(11)C] leucine PET method are not significantly altered by anesthesia with propofol. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1035-1047; doi:10.1038/jcbfm.2009.7; published online 18 February 2009 C1 [Bishu, Shrinivas; Schmidt, Kathleen C.; Burlin, Thomas V.; Huang, Tianjiang; Liu, Zhong-hua; Qin, Mei; Unterman, Aaron J.; Xia, Zengyan; Zametkin, Alan; Smith, Carolyn B.] NIMH, Sect Neuroadaptat & Prot Metab, Bethesda, MD 20892 USA. [Channing, Michael A.; Vuong, B-K; Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. [Horowitz, Lisa] NIMH, Off Clin Director, Bethesda, MD 20892 USA. [Quezado, Zenaide] NIH, Dept Anesthesia & Surg Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Bishu, S (reprint author), NIMH, Sect Neuroadaptat & Prot Metab, Bldg 10,Rm 2D54,10 Ctr Dr, Bethesda, MD 20892 USA. EM bishus@mail.nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU National Institute of Mental Health; Clinical Center, National Institutes of Health; Fragile X Research Foundation FX This research was supported by the Intramural Research Program, National Institute of Mental Health; Clinical Center, National Institutes of Health; Fragile X Research Foundation. NR 45 TC 10 Z9 10 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2009 VL 29 IS 5 BP 1035 EP 1047 DI 10.1038/jcbfm.2009.7 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 439PU UT WOS:000265640300017 PM 19223912 ER PT J AU Ghysels, A Van Speybroeck, V Pauwels, E Van Neck, D Brooks, BR Waroquier, M AF Ghysels, A. Van Speybroeck, V. Pauwels, E. Van Neck, D. Brooks, B. R. Waroquier, M. TI Mobile Block Hessian Approach with Adjoined Blocks: An Efficient Approach for the Calculation of Frequencies in Macromolecules SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID NORMAL-MODE ANALYSIS; ALANINE DIPEPTIDE; AB-INITIO; CLUSTER CALCULATIONS; VIBRATIONAL ANALYSIS; METHOXY ADSORPTION; PROTEIN DYNAMICS; FERMI RESONANCES; AQUEOUS-SOLUTION; SIMULATIONS AB In an earlier work, the authors developed a new method, the mobile block Hessian (MBH) approach, to accurately calculate vibrational modes for partially optimized molecular structures [J. Chem. Phys. 2007, 126 (22), 224102.]. It is based on the introduction of blocks, consisting of groups of atoms, that can move as rigid bodies. The internal geometry of the blocks need not correspond to an overall optimization state of the total molecular structure. The standard MBH approach considers free blocks with six degrees of freedom. In the extended MBH approach introduced herein, the blocks can be connected by one or two adjoining atoms, which further reduces the number of degrees of freedom. The new approach paves the way for the normal-mode analysis of biomolecules such as proteins. It rests on the hypothesis that low-frequency modes of proteins can be described as pure rigid-body motions of blocks of consecutive amino acid residues. The method is validated for a series of small molecules and further applied to alanine dipeptide as a prototype to describe vibrational interactions between two peptide units; to crambin, a small protein with 46 amino acid residues; and to ICE/caspase-1, which contains 518 amino acid residues. C1 [Ghysels, A.; Van Speybroeck, V.; Pauwels, E.; Van Neck, D.; Waroquier, M.] Univ Ghent, Ctr Mol Modeling, B-9000 Ghent, Belgium. [Brooks, B. R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Waroquier, M (reprint author), Univ Ghent, Ctr Mol Modeling, Proeftuinstr 86, B-9000 Ghent, Belgium. EM Michel.Waroquier@UGent.be RI Ghysels, An/M-9095-2015 FU Fund for Scientific Research - Flanders (FWO); Research Board of Ghent University (BOF); Belgian Program on Interuniversity Attraction Poles (IAP) FX A.G. is Aspirant of the Fund for Scientific Research - Flanders (FWO). This work was by the Fund for Scientific Research - Flanders (FWO), the Research Board of Ghent University (BOF), and the Belgian Program on Interuniversity Attraction Poles (IAP). NR 44 TC 22 Z9 23 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD MAY PY 2009 VL 5 IS 5 BP 1203 EP 1215 DI 10.1021/ct800489r PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 444OT UT WOS:000265991000002 PM 26609711 ER PT J AU Khalili, M Wales, DJ AF Khalili, Mey Wales, David J. TI Computer Simulations of Peptides from the p53 DNA Binding Domain SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID TUMOR-SUPPRESSOR P53; SECONDARY STRUCTURE PREDICTION; PARTICLE MESH EWALD; MOLECULAR-DYNAMICS; GENE-THERAPY; LUNG-CANCER; FORCE-FIELD; SV40-TRANSFORMED CELLS; TRANSACTIVATION DOMAIN; CRYSTAL-STRUCTURE AB We have studied the dynamics and thermodynamics of two of the four evolutionarily conserved segments from the p53 DNA binding domain, using molecular dynamics and replica exchange simulations. These two regions contain well-defined elements of secondary structure (a beta hairpin for region II and an alpha helix for region V) and bind to DNA in the intact protein. They are also mutational hot spots. The goal of our study was to determine the stability and folding propensity of these peptides in isolation. We used three force fields and solvent models (CHARMM19 with EEF1, CHARMM27 with GBMV, GROMOS96 with SPC). The predicted stability, folding propensity, and secondary structures depend upon the potential. Secondary structure predictors identify helical propensity for region II, in agreement with one of the force fields (CHARMM/GBMV). However, the other two potentials favor beta structure for this peptide, although the conformations may differ from the crystal. For region V secondary structure predictions are unclear. Only one force field (CHARMM/GBMV) produces low-lying free energy minima that retain some of the alpha helical structure from the crystal structure. The other two potentials appear to favor beta structure for this peptide. C1 [Wales, David J.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. [Khalili, Mey] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Khalili, Mey] Mitre Corp, Mclean, VA 22102 USA. RP Wales, DJ (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM dw34@cam.ac.uk NR 97 TC 4 Z9 4 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD MAY PY 2009 VL 5 IS 5 BP 1380 EP 1392 DI 10.1021/ct8005387 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 444OT UT WOS:000265991000020 PM 26609726 ER PT J AU Rosta, E Buchete, NV Hummer, G AF Rosta, Edina Buchete, Nicolae-Viorel Hummer, Gerhard TI Thermostat Artifacts in Replica Exchange Molecular Dynamics Simulations SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID CANONICAL ENSEMBLE; EQUILIBRIUM; TEMPERATURE; PROTEIN; ALGORITHMS; PRESSURE; PEPTIDE; SYSTEMS; BATH AB We explore the effects of thermostats in replica exchange molecular dynamics (REMD) simulations. For thermostats that do not produce a canonical ensemble, REMD simulations are found to distort the configuration-space distributions. For bulk water, we find small deviations of the average potential energies, the buildup of tails in the potential energy distributions, and artificial correlations between the energies at different temperatures. If a solute is present, as in protein folding simulations, its conformational equilibrium can be altered. In REMD simulations of a helix-forming peptide with a weak-coupling (Berendsen) thermostat, we find that the folded state is overpopulated by about 10% at low temperatures, and underpopulated at high temperatures. As a consequence, the enthalpy of folding deviates by almost 3 kcal/mol from the correct value. The reason for this population shift is that noncanonical ensembles with narrowed potential energy fluctuations artificially bias toward replica exchanges between low-energy folded structures at the high temperature and high-energy unfolded structures at the low temperature. We conclude that REMD simulations should only be performed in conjunction with thermostats that produce a canonical ensemble. C1 [Rosta, Edina; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Buchete, Nicolae-Viorel] Univ Coll Dublin, Sch Phys, Dublin 4, Ireland. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM Gerhard.Hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; Buchete, Nicolae-Viorel/C-6200-2015; OI Hummer, Gerhard/0000-0001-7768-746X; Buchete, Nicolae-Viorel/0000-0001-9861-1157; Rosta, Edina/0000-0002-9823-4766 FU National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX We thank Dr. Attila Szabo for many helpful and stimulating discussions and Dr. Nicolas Fawzi for his valuable comments. This research used the Biowulf Linux cluster at the National Institutes of Health (NIH), and the Irish Centre for High-End Computing (ICHEC). E.R. and G.H. were supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 30 TC 48 Z9 48 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD MAY PY 2009 VL 5 IS 5 BP 1393 EP 1399 DI 10.1021/ct800557h PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 444OT UT WOS:000265991000021 PM 20046980 ER PT J AU Lateef, TM Merikangas, KR He, JP Kalaydjian, A Khoromi, S Knight, E Nelson, KB AF Lateef, Tarannum M. Merikangas, Kathleen R. He, Jianping Kalaydjian, Amanda Khoromi, Suzan Knight, Erin Nelson, Karin B. TI Headache in a National Sample of American Children: Prevalence and Comorbidity SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE headache; migraine; comorbidity; prevalence ID IHS CRITERIA; YOUNG-ADULTS; DIAGNOSTIC-CRITERIA; PEDIATRIC MIGRAINE; GENERAL-PRACTICE; CHILDHOOD; AGE; ASTHMA; ASSOCIATION; ADOLESCENTS AB The purpose of this study was to determine the prevalence, sociodemographic correlates, and comorbidity of recurrent headache in children in the United States. Participants were individuals aged 4 to 18 years (n = 10198) who participated in the National Health and Nutrition Examination Surveys. Data on recurrent and other health conditions were analyzed. Frequent or severe headaches including migraine in the past 12 months were reported in 17.1% of children. Asthma, hay fever, and frequent ear infections were more common in children with headache, with at least 1 of these occuring in 41.6% of children with headache versus 25.0% of children free of headache. Other medical problems associated with childhood headaches include anemia, overweight, abdominal illnesses, and early menarche. Recurrent headache in childhood is common and has significant medical comorbidity. Further research is needed to understand biologic mechanisms and identify more homogeneous subgroups in clinical and genetic studies. C1 [Lateef, Tarannum M.; Nelson, Karin B.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Lateef, Tarannum M.; Nelson, Karin B.] George Washington Univ, Sch Med, Washington, DC USA. [Merikangas, Kathleen R.; He, Jianping; Kalaydjian, Amanda; Khoromi, Suzan; Knight, Erin] NIMH, Intramural Res Program, Bethesda, MD 20892 USA. [Nelson, Karin B.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Lateef, TM (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave, Washington, DC 20010 USA. EM tlateef@cnmc.org FU National Institute of Neurological Disorders and Stroke FX This work is supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. NR 42 TC 53 Z9 53 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2009 VL 24 IS 5 BP 536 EP 543 DI 10.1177/0883073808327831 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 437RW UT WOS:000265505600002 PM 19406755 ER PT J AU Issaq, HJ Blonder, J AF Issaq, Haleem J. Blonder, Josip TI Electrophoresis and liquid chromatography/tandem mass spectrometry in disease biomarker discovery SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE Disease biomarkers; HPLC-MS/MS; Proteomics; Metabolomics ID GEL-ELECTROPHORESIS; PROTEOMIC PATTERNS; AFFINITY-CHROMATOGRAPHY; PLASMA PROTEOMICS; SERUM PROTEOME; OVARIAN-CANCER; QUANTITATION; PEPTIDES; PROTEINS; TECHNOLOGIES AB The search for disease markers is not new; however, with the emergence of new technologies such as nano-HPLC and electrospray ionization and time of flight mass spectrometry, the search has intensified considerably. Genomic, proteomic and metabolomic technologies are being used to search for novel disease markers. In this manuscript emphasis will be on different HPLC and MS methods that are used to search for metabolites and proteins that can be used for the discovery of novel, sensitive and specific disease biomarkers. Definitions of terms such as sensitivity, specificity. and protein profiles will be given. Methods used for effective fractionation, separation and quantitation of proteins and peptides using HPLC/MS will be discussed and examples are presented. A brief discussion of electrophoretic procedures used for protein fractionation and biomarker discovery is also included. (C) 2008 Elsevier B.V. All rights reserved. C1 [Issaq, Haleem J.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 59 TC 20 Z9 20 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 1 PY 2009 VL 877 IS 13 BP 1222 EP 1228 DI 10.1016/j.jchromb.2008.12.028 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 441IZ UT WOS:000265763800002 PM 19117811 ER PT J AU Farlow, DW Xu, X Veenstra, TD AF Farlow, Daniel W. Xu, Xia Veenstra, Timothy D. TI Quantitative measurement of endogenous estrogen metabolites, risk-factors for development of breast cancer, in commercial milk products by LC-MS/MS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Estrogen metabolites; Milk; Breast cancer; Biomarkers; Selected reaction monitoring mass spectrometry ID CHROMATOGRAPHY-MASS SPECTROMETRY; ESTRADIOL; THERAPY; HORMONES; ASSAY AB Increased levels of estrogen metabolites (EM) are associated with cancers of the reproductive system. One potential dietary source of EM is milk. In this study, the absolute quantities of unconjugated (free) and unconjugated plus conjugated (total) EM were measured in a variety of commercial milks (whole, 2%, skim, and buttermilk). The results show that the milk products tested contain considerable levels of EM; however, the levels of unconjugated EM in skim milk were substantially lower than that observed in whole milk, 2% milk, and buttermilk. Whole milk contained the lowest overall levels of EM while buttermilk contained the highest. As anticipated, soy milk did not contain the mammalian EM measured using this method. The relatively high levels of catechol estrogens detected in milk products support the theory that milk consumption is a source of EM and their ingestion may have a dietary influence on cancer risk. (C) 2009 Elsevier B.V. All rights reserved. C1 [Farlow, Daniel W.; Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the United States Government. NR 21 TC 38 Z9 40 U1 1 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAY 1 PY 2009 VL 877 IS 13 BP 1327 EP 1334 DI 10.1016/j.jchromb.2009.01.032 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 441IZ UT WOS:000265763800013 PM 19217359 ER PT J AU Debono, M Ghobadi, C Rostami-Hodjegan, A Huatan, H Campbell, MJ Newell-Price, J Darzy, K Merke, DP Arlt, W Ross, RJ AF Debono, Miguel Ghobadi, Cyrus Rostami-Hodjegan, Amin Huatan, Hiep Campbell, Michael J. Newell-Price, John Darzy, Ken Merke, Deborah P. Arlt, Wiebke Ross, Richard J. TI Modified-Release Hydrocortisone to Provide Circadian Cortisol Profiles SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBJECTIVE HEALTH-STATUS; ADRENAL INSUFFICIENCY; ADDISONS-DISEASE; PREMATURE MORTALITY; PLASMA-CORTISOL; SERUM CORTISOL; RHYTHMS; MELATONIN; PITUITARY; HORMONES AB Context: Cortisol has a distinct circadian rhythm regulated by the brain's central pacemaker. Loss of this rhythm is associated with metabolic abnormalities, fatigue, and poor quality of life. Conventional glucocorticoid replacement cannot replicate this rhythm. Objectives: Our objectives were to define key variables of physiological cortisol rhythm, and by pharmacokinetic modeling test whether modified-release hydrocortisone (MR-HC) can provide circadian cortisol profiles. Setting: The study was performed at a Clinical Research Facility. Design and Methods: Using data from a cross-sectional study in healthy reference subjects (n = 33), we defined parameters for the cortisol rhythm. We then tested MR-HC against immediate-release hydrocortisone in healthy volunteers (n = 28) in an open-label, randomized, single-dose, cross-over study. We compared profiles with physiological cortisol levels, and modeled an optimal treatment regimen. Results: The key variables in the physiological cortisol profile included: peak 15.5 mu g/dl (95% reference range 11.7-20.6), acrophase 0832 h(95% confidence interval 0759-0905), nadir less than 2 mu g/dl (95% reference range 1.5-2.5), time of nadir 0018 h (95% confidence interval 2339-0058), and quiescent phase (below the mesor) 1943-0531 h. MR-HC 15 mg demonstrated delayed and sustained release with a mean (SEM) maximum observed concentration of 16.6 (1.4) mu g/dl at 7.41 (0.57) h after drug. Bioavailability of MR-HC 5, 10, and 15 mg was 100, 79, and 86% that of immediate-release hydrocortisone. Modeling suggested that MR-HC 15-20 mg at 2300 h and 10 mg at 0700 h could reproduce physiological cortisol levels. Conclusion: By defining circadian rhythms and using modern formulation technology, it is possible to allow a more physiological circadian replacement of cortisol. (J Clin Endocrinol Metab 94: 1548-1554, 2009) C1 [Debono, Miguel; Newell-Price, John; Ross, Richard J.] Univ Sheffield, Royal Hallamshire Hosp, Acad Unit Diabet Endocrinol & Reprod, Sch Med, Sheffield S10 2JF, S Yorkshire, England. [Ghobadi, Cyrus; Rostami-Hodjegan, Amin] Univ Sheffield, Royal Hallamshire Hosp, Acad Unit Clin Pharmacol, Sch Med, Sheffield S10 2JF, S Yorkshire, England. [Campbell, Michael J.] Univ Sheffield, Hlth Serv Res Sheffield Sch Hlth & Related Res, Sheffield S1 4DA, S Yorkshire, England. [Darzy, Ken] E&N Hertfordshire Natl Hlth Serv Trust, Welwyn Garden City AL7 4HQ, Herts, England. [Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Arlt, Wiebke] Univ Birmingham, Ctr Endocrinol Diabet & Metab, Sch Clin & Expt Med, Birmingham B15 2TT, W Midlands, England. RP Ross, RJ (reprint author), Univ Sheffield, Royal Hallamshire Hosp, Acad Unit Diabet Endocrinol & Reprod, Sch Med, Room 112,Floor M,Glossop Rd, Sheffield S10 2JF, S Yorkshire, England. EM r.j.ross@sheffield.ac.uk RI Arlt, Wiebke/B-6310-2009; Ross, Richard/B-2672-2012; OI Arlt, Wiebke/0000-0001-5106-9719; Ross, Richard/0000-0001-9222-9678; Campbell, Michael/0000-0003-3529-2739 FU Diurnal Ltd.; Phoqus Pharmaceuticals, plc.; National Institutes of Health [G116/172] FX The study was funded by Diurnal Ltd. and Phoqus Pharmaceuticals, plc. W. A. is a Medical Research Council Senior Clinical Fellow (G116/172). This research was supported (in part) by the Intramural Research Program of the National Institutes of Health.; Disclosure Summary: M. D., C. G., M.J.C., J.N.-P.,K. D., and W. A. have nothing to declare. D. P. M. received research funds from Phoqus Pharmaceuticals, plc. R.J.R. and A. R.-H. have equity interests in Diurnal Ltd. H. H. is employed as a consultant for Diurnal Ltd. NR 33 TC 93 Z9 95 U1 1 U2 16 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2009 VL 94 IS 5 BP 1548 EP 1554 DI 10.1210/jc.2008-2380 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442OW UT WOS:000265851500012 PM 19223520 ER PT J AU Agarwal, SK Mateo, CM Marx, SJ AF Agarwal, Sunita K. Mateo, Carmen M. Marx, Stephen J. TI Rare Germline Mutations in Cyclin-Dependent Kinase Inhibitor Genes in Multiple Endocrine Neoplasia Type 1 and Related States SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-SUPPRESSOR; P27(KIP1); P16(INK4A)/CDKN2A; IDENTIFICATION; P18(INK4C); VARIANTS; CANCER; MICE; HYPERPARATHYROIDISM; BINDING AB Context: Germline mutation in the MEN1 gene is the usual cause of multiple endocrine neoplasia type 1 (MEN1). However, the prevalence of identifiable germline MEN1 mutations in familial MEN1 cases is only 70%. Some cases may have a germline mutation in another gene such as the p27 cyclin-dependent kinase inhibitor (CDKI). Objective: The aim of the study was to investigate cases of MEN1 or related states for germline mutations in all CDKI genes. Methods: A total of 196 consecutive index cases were selected with clear or suspected MEN1 and no identifiable germline MEN1 mutation. Every case was analyzed for germline mutation in each of the seven CDKI genes. Results: We identified benign polymorphisms of the CDKI genes and also 15 other initially unclassified sequence variants. After detailed gene/protein analysis, seven of these 15 variants were classified as probably pathological mutations. Three of these seven were probable mutations of p27. The remaining four were probable pathological mutations in three of the other CDKI genes, thereby implicating these three genes in the germline of human tumors. The identification rates for probably pathological mutations among the 196 index cases were similarly low for each of four CDKI genes: p15 (1%), p18 (0.5%), p21 (0.5%), and p27 (1.5%). No characteristic clinical subtype related to MEN1 was identified among the seven index cases and their families. Conclusion: Rare germline mutation in any among four (p15, p18, p21, and p27) of the seven CDKIs is a probable cause of MEN1 or of some related states. (J Clin Endocrinol Metab 94: 1826-1834, 2009) C1 [Agarwal, Sunita K.; Mateo, Carmen M.; Marx, Stephen J.] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIDDKD, NIH, Bldg 10,Room 9C-103, Bethesda, MD 20892 USA. EM SunitaA@mail.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 40 TC 120 Z9 127 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2009 VL 94 IS 5 BP 1826 EP 1834 DI 10.1210/jc.2008-2083 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442OW UT WOS:000265851500055 PM 19141585 ER PT J AU Buono, C Anzinger, JJ Amar, M Kruth, HS AF Buono, Chiara Anzinger, Joshua J. Amar, Marcelo Kruth, Howard S. TI Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; FOAM CELL-FORMATION; SCAVENGER-RECEPTOR-A; CHOLESTEROL ACCUMULATION; RETICULOENDOTHELIAL SYSTEM; HUMAN MONOCYTES; BINDING-SITE; MICE; LDL; MACROPINOCYTOSIS AB The uptake of lipoproteins by macrophages is a critical step in the development of atherosclerotic lesions. Cultured monocyte-derived macrophages take up large amounts of native LDL by receptor-independent fluid-phase pinocytosis, either constitutively or in response to specific activating stimuli, depending on the macrophage phenotype. We therefore sought to determine whether fluid-phase pinocytosis occurs in vivo in macrophages in atherosclerotic lesions. We demonstrated that fluorescent pegylated nanoparticles similar in size to LDL (specifically nontargeted Qtracker quantum dot and AngioSPARK nanoparticles) can serve as models of LDL uptake by fluid-phase pinocytosis in cultured human monocyte-derived macrophages and mouse bone marrow-derived macrophages. Using fluorescence microscopy, we showed that atherosclerosis-prone Apoe-knockout mice injected with these nanoparticles displayed massive accumulation of the nanoparticles within CD68(+) macrophages, including lipid-containing foam cells, in atherosclerotic lesions in the aortic arch. Similar results were obtained when atherosclerotic mouse aortas were cultured with nanoparticles in vitro. These results show that macrophages within atherosclerotic lesions can take up LDL-sized nanoparticles by fluid-phase pinocytosis and indicate that fluid-phase pinocytosis of LDL is a mechanism for macrophage foam cell formation in vivo. C1 [Buono, Chiara; Anzinger, Joshua J.; Kruth, Howard S.] NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. [Amar, Marcelo] NHLBI, Mol Dis Sect, NIH, Bethesda, MD 20892 USA. [Buono, Chiara] VisEn Med, Bedford, MA USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Room 5N-113,10 Ctr Dr MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU VisEn Medical; NHLBI; NIH FX We also thank Sylvie Kossodo and Jeff Peterson for advice and support for the portion of the study carried out at VisEn Medical. This research was supported in part by the Intramural Research Program of the NHLBI, NIH. NR 40 TC 40 Z9 45 U1 0 U2 18 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2009 VL 119 IS 5 BP 1373 EP 1381 DI 10.1172/JCI35548 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 442LT UT WOS:000265843400035 PM 19363293 ER PT J AU Shea, YR Davis, JL Huang, L Kovacs, JA Masur, H Mulindwa, F Opus, S Chow, Y Murray, PR AF Shea, Yvonne R. Davis, J. Lucian Huang, Laurence Kovacs, Joseph A. Masur, Henry Mulindwa, Francis Opus, Sally Chow, Yuenwah Murray, Patrick R. TI High Sensitivity and Specificity of Acid-Fast Microscopy for Diagnosis of Pulmonary Tuberculosis in an African Population with a High Prevalence of Human Immunodeficiency Virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SPUTUM SMEAR MICROSCOPY; FLUORESCENCE; SECA1 AB Laboratories in low-income countries report that acid-fast microscopy is insensitive and nonspecific. We demonstrate that for a Ugandan population with high prevalences of tuberculosis and human immunodeficiency virus infection, acid-fast microscopy is highly sensitive (93.1%) and specific (100%) when performed by trained technologists in a carefully controlled manner using established techniques. C1 [Shea, Yvonne R.; Chow, Yuenwah; Murray, Patrick R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Davis, J. Lucian; Huang, Laurence] San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Davis, J. Lucian; Huang, Laurence] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Davis, J. Lucian; Huang, Laurence; Mulindwa, Francis; Opus, Sally] Univ Calif San Francisco Res Collaborat, Makerere Univ, Kampala, Uganda. [Kovacs, Joseph A.; Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Mulindwa, Francis; Opus, Sally] Mulago Hosp, Kampala, Uganda. RP Murray, PR (reprint author), NIH, Dept Lab Med, Ctr Clin, Room 2C385,10 Ctr Dr, Bethesda, MD 20892 USA. EM Pmurray@cc.nih.gov FU NIH [K24 HL087713, 1K23AI080147] FX We do not have an association that might bias this study. NR 12 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2009 VL 47 IS 5 BP 1553 EP 1555 DI 10.1128/JCM.00348-09 PG 3 WC Microbiology SC Microbiology GA 439QB UT WOS:000265641000042 PM 19297594 ER PT J AU Palmore, TN Shea, YR Conville, PS Witebsky, FG Anderson, VL Hodge, IPR Holland, SM AF Palmore, Tara N. Shea, Yvonne R. Conville, Patricia S. Witebsky, Frank G. Anderson, Victoria L. Hodge, Irene P. Rupp Holland, Steven M. TI "Mycobacterium tilburgii," a Newly Described, Uncultivated Opportunistic Pathogen SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL-RNA GENE; IDENTIFICATION; BACTERIA; PATIENT AB Molecular methods are increasingly used to identify pathogens that are difficult to cultivate. We report a case of disseminated infection with "Mycobacterium tilburgii," a proposed species that has never been cultivated. The case illustrates the diagnostic utility of sequence analysis of the 16S rRNA gene directly from clinical specimens. C1 [Palmore, Tara N.; Anderson, Victoria L.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Shea, Yvonne R.; Conville, Patricia S.; Witebsky, Frank G.] NIH, Microbiol Serv, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Hodge, Irene P. Rupp] Frisbie Mem Hosp, Rochester, NH USA. RP Palmore, TN (reprint author), 10 Ctr Dr,Room 12C103A, Bethesda, MD 20892 USA. EM tpalmore@mail.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health Clinical Center FX research was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases and the National Institutes of Health Clinical Center. NR 9 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2009 VL 47 IS 5 BP 1585 EP 1587 DI 10.1128/JCM.02385-08 PG 3 WC Microbiology SC Microbiology GA 439QB UT WOS:000265641000052 PM 19261797 ER PT J AU Chew, HK Doroshow, JH Frankel, P Margolin, KA Somlo, G Lenz, HJ Gordon, M Zhang, W Yang, DY Russell, C Spicer, D Synold, T Bayer, R Hantel, A Stiff, PJ Tetef, ML Gandara, DR Albain, KS AF Chew, Helen K. Doroshow, James H. Frankel, Paul Margolin, Kim A. Somlo, George Lenz, Heinz-Josef Gordon, Michael Zhang, Wu Yang, Dongyun Russell, Christy Spicer, Darcy Synold, Tim Bayer, Robert Hantel, Alexander Stiff, Patrick J. Tetef, Merry L. Gandara, David R. Albain, Kathy S. TI Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; PLUS CISPLATIN; ADJUVANT CHEMOTHERAPY; POLYMORPHISMS; XRCC3; PACLITAXEL; REPAIR; TRIAL; CARBOPLATIN; COMBINATION AB Purpose Cisplatin and gemcitabine have single-agent activity in metastatic breast cancer, and preclinical data support synergy of the combination. Two parallel, phase II trials were conducted to evaluate the response rate, response duration, and toxicities of the combination. Genetic polymorphisms were analyzed for correlation with outcomes. Patients and Methods Eligible women had measurable disease and heavily or minimally pretreated metastatic breast cancer. The heavily pretreated protocol required prior anthracycline and taxane therapy; cisplatin as part of high-dose therapy was allowed. All patients received cisplatin 25 mg/m(2) on days 1 through 4 and gemcitabine 1,000 mg/m2 on days 2 and 8 of a 21-day cycle with prophylactic granulocyte colony-stimulating factor in the heavily pretreated group. Sera from a subset of patients were evaluated by polymerase chain reaction restriction fragment length polymorphism for polymorphisms in 10 genes of interest. Results Of 136 women enrolled, 74 were heavily pretreated. Both protocols accrued to their two-stage design. The response rate for both the heavily and minimally pretreated cohorts was 26%, and the median durations of response were 5.3 and 5.9 months, respectively. In a multivariate analysis, hormone receptor-negative disease was associated with a higher response rate. The most common grades 3 or 4 toxicities were thrombocytopenia (71%), neutropenia (66%), and anemia (38%). In a subset of 55 patients, the xeroderma pigmentosum group D (XPD)-751, x-ray cross-complementing group 3 (XRCC3) and cytidine deaminase polymorphisms were significantly associated with clinical outcomes. Conclusion Combination cisplatin and gemcitabine is active in metastatic breast cancer regardless of prior therapy. Genetic polymorphisms may tailor which patients benefit from this regimen. C1 [Chew, Helen K.] Univ Calif Davis, Dept Internal Med, Div Hematol Oncol, Sacramento, CA 95817 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Loyola Univ Chicago, Stritch Sch Med, Dept Med, Div Hematol Oncol, Maywood, IL USA. RP Chew, HK (reprint author), Univ Calif Davis, Dept Internal Med, Div Hematol Oncol, 4501 X St,Ste 3016, Sacramento, CA 95817 USA. EM helen.chew@ucdmc.ucdavis.edu RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Eli Lilly; [N01-CM17101] FX Supported in part by Award No. N01-CM17101 to the California Cancer Consortium and by a grant from Eli Lilly. NR 24 TC 39 Z9 41 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2009 VL 27 IS 13 BP 2163 EP 2169 DI 10.1200/JCO.2008.17.4839 PG 7 WC Oncology SC Oncology GA 447MK UT WOS:000266195000011 PM 19307510 ER PT J AU Moore, GJ Cortese, BM Glitz, DA Zajac-Benitez, C Quiroz, JA Uhde, TW Drevets, WC Manji, HK AF Moore, Gregory J. Cortese, Bernadette M. Glitz, Debra A. Zajac-Benitez, Caroline Quiroz, Jorge A. Uhde, Thomas W. Drevets, Wayne C. Manji, Husseini K. TI A Longitudinal Study of the Effects of Lithium Treatment on Prefrontal and Subgenual Prefrontal Gray Matter Volume in Treatment-Responsive Bipolar Disorder Patients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; MOOD DISORDERS; CELL-SURVIVAL; SUICIDE RISK; HUMAN BRAIN; IN-VIVO; DEPRESSION; NEUROBIOLOGY; HIPPOCAMPUS; CASCADES AB Objective: Recent molecular, preclinical, and preliminary clinical studies suggest that the therapeutic effects of mood stabilizers may be mediated by modulating expression of potent neurotrophic and neuroprotective factors having the potential to reverse impairments of cellular resilience, reductions in brain volume, and cell death or atrophy. Our main goal was to investigate the potential clinical significance of these findings in relation to bipolar disorder. Methods: The longitudinal effect of lithium on brain gray matter volume was investigated in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at baseline (medication-free) and after lithium administration (4 weeks). Total brain gray matter prefrontal gray matter, and left subgenual prefrontal gray matter volumes were determined using validated semiautomated segmentation and region of interest methodology. The study was conducted from November 1997 until April 2004 at Wayne State University School of Medicine, Detroit, Mich. Results: Significant increases in total brain gray matter volume in bipolar subjects were observed after 4 weeks of lithium administration (p =.(1(143). Moreover, regional analyses in the bipolar subjects revealed significant differences between responders (> 50% decrease in Hamilton Depression Rating Scale total score) and nonresponders; only responders showed a significant increase in gray matter volume in the prefrontal cortex (p = .003) and an increase at trend level in the left subgenual prefrontal cortex volume (p = .0786). Conclusions: The increase in gray matter volume in these areas, which various neuroimaging and postmortem neuropathology studies have implicated in the neuropathophysiology of bipolar disorder, suggests that the observed effects may be linked to clinical response. The findings also support the notion that future treatments that more directly target molecules in critical central nervous system pathways that regulate cellular plasticity hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease. Trial Registration: clinicaltrials.gov Identifier NCT00870311. J Clin Psychiatry 2009;70(5):699-705 (C) Copyright 2009 Physicians Postgraduate Press. Inc. C1 [Moore, Gregory J.; Cortese, Bernadette M.; Uhde, Thomas W.; Manji, Husseini K.] Penn State Univ, Coll Med, Behav Neuroimaging Res Div, Dept Psychiat, Hershey, PA USA. [Moore, Gregory J.; Cortese, Bernadette M.; Uhde, Thomas W.; Manji, Husseini K.] Penn State Neurosci Inst, Dept Radiol, Hershey, PA 17033 USA. [Glitz, Debra A.; Zajac-Benitez, Caroline] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Quiroz, Jorge A.; Drevets, Wayne C.; Manji, Husseini K.] NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Moore, GJ (reprint author), Penn State Neurosci Inst, Ctr Emerging Neurotechnol & Imaging, 500 Univ Dr H073, Hershey, PA 17033 USA. EM gmoore@psu.edu RI Moore, Gregory/E-7184-2010 OI Moore, Gregory/0000-0001-8541-3194 FU National Institute of Mental Health [MH59107]; NARSAD; Stanley Foundation FX This work was supported by grants from the National Institute of Mental Health (MH59107), NARSAD, and the Stanley Foundation to Drs. Moore and Manji. NR 41 TC 104 Z9 105 U1 0 U2 21 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2009 VL 70 IS 5 BP 699 EP 705 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 450TO UT WOS:000266424000010 PM 19389332 ER PT J AU Vitiello, B Silva, SG Rohde, P Kratochvil, CJ Kennard, BD Reinecke, MA Mayes, TL Posner, K May, DE March, JS AF Vitiello, Benedetto Silva, Susan G. Rohde, Paul Kratochvil, Christopher J. Kennard, Betsy D. Reinecke, Mark A. Mayes, Taryn L. Posner, Kelly May, Diane E. March, John S. TI Suicidal Events in the Treatment for Adolescents With Depression Study (TADS) SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT TREATMENT; RISK; PSYCHOTHERAPY; RELIABILITY; VALIDITY; TRIAL AB Objective: The Treatment for Adolescents with Depression Study (TADS) database was analyzed to determine whether suicidal events (attempts and ideation) occurred early in treatment, could be predicted by severity of depression or other clinical characteristics, and were preceded by clinical deterioration or symptoms of increased irritability, akathisia, sleep disruption, or mania. Method: TADS was a 36-week randomized, controlled clinical trial of pharmacologic and psychotherapeutic treatments involving 439 youths with major depressive disorder (DSM-IV criteria). Suicidal events were defined according to the Columbia Classification Algorithm of Suicidal Assessment. Patients were randomly assigned into the study between spring 2000 and summer 2003. Results: Forty-four patients (10.0%) had at least 1 suicidal event (no suicide occurred). Events occurred 0.4 to 31.1 weeks (mean +/- SD = 11.9 +/- 8.2) after starting TADS treatment, with no difference in event timing for patients receiving medication versus those not receiving medication. Severity of self-rated pretreatment suicidal ideation (Suicidal Ideation Questionnaire adapted for adolescents score >= 31) and depressive symptoms (Reynolds Adolescent Depression Scale score >= 91) predicted occurrence of suicidal events during treatment (P < .05). Patients with suicidal events were on average still moderately ill prior to the event (mean +/- SD Clinical Global Impressions-Severity of Illness scale score = 4.0 +/- 1.3) and only minimally improved (mean +/- SD Clinical Global Impressions-Improvement scale score = 3.2 +/- 1.1). Events were not preceded by increased irritability, akathisia, sleep disturbance, or manic signs. Specific interpersonal stressors were identified in 73% of cases (N = 44). Of the events, 55% (N = 24) resulted in overnight hospitalization. Conclusions: Most suicidal events occurred in the context of persistent depression and insufficient improvement without evidence of medication-induced behavioral activation as a precursor. Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment. Risk for suicidal events did not decrease after the first month of treatment, suggesting the need for careful clinical monitoring for several months after starting treatment. J Clin Psychiatry 2009;70(5):741-747 (C) Copyright 2009 Physicians Postgraduate Press, Inc. C1 [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. [Silva, Susan G.; March, John S.] Duke Clin Res Inst, Durham, NC USA. [Silva, Susan G.; March, John S.] Duke Univ, Med Ctr, Durham, NC USA. [Kratochvil, Christopher J.; May, Diane E.] Univ Nebraska, Omaha, NE 68182 USA. [Rohde, Paul] Univ Oregon, Eugene, OR 97403 USA. [Kennard, Betsy D.; Mayes, Taryn L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Reinecke, Mark A.] Northwestern Univ, Chicago, IL 60611 USA. [Posner, Kelly] Columbia Univ, New York, NY USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiello@mail.nih.gov FU National Institute of Mental Health, Bethesda, MD [N01 MH80008] FX The Treatment for Adolescents with Depression Study was supported by contract N01 MH80008 from the National Institute of Mental Health, Bethesda, MD, to Duke University Medical Center Durham, NC. NR 26 TC 49 Z9 49 U1 1 U2 13 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2009 VL 70 IS 5 BP 741 EP 747 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 450TO UT WOS:000266424000015 PM 19552869 ER PT J AU Jones, JL Lucker, J Zalewski, C Brewer, C Drayna, D AF Jones, Jennifer L. Lucker, Jay Zalewski, Christopher Brewer, Carmen Drayna, Dennis TI Phonological processing in adults with deficits in musical pitch recognition SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article ID AUDITORY-CORTEX; CONGENITAL AMUSIA; TUNE DEAFNESS; BRAIN; PERCEPTION; DISORDER AB We identified individuals with deficits in musical pitch recognition by screening a large random population using the Distorted Tunes Test (DTT), and enrolled individuals who had DTT scores in the lowest 10th percentile, classified as tune deaf. We examined phonological processing abilities in 35 tune deaf and 34 normal control individuals. Eight different tests of phonological processing, including auditory word discrimination, syllable segmentation, and the Comprehensive Test of Phonological Processing (CTOPP) were administered to both groups. The tune deaf group displayed lower phonological and phonemic awareness abilities on all measures. Our results indicate that poor performance on the DTT is associated with deficits in processing speech sounds. These findings support the hypothesis that processing of speech sounds and musical sounds share common elements, and that tune deafness may be viewed as a syndromic disorder, frequently accompanied by deficits in a number of aspects of sound processing not specific to music. Learning outcomes: The reader will (1) understand the broad range of deficits in phonological perception and processing that accompany deficits in musical pitch recognition, and (2) recognize the possible utility of musical evaluation measures and music-based therapies in the treatment of phonological and other speech disorders. Published by Elsevier Inc. C1 [Jones, Jennifer L.; Zalewski, Christopher; Brewer, Carmen; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Jones, Jennifer L.; Lucker, Jay] Howard Univ, Dept Commun Sci & Disorders, Washington, DC 20059 USA. RP Drayna, D (reprint author), NIDCD, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov FU Intramural NIH HHS [Z01 DC000046-08] NR 32 TC 29 Z9 29 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-9924 J9 J COMMUN DISORD JI J. Commun. Disord. PD MAY-JUN PY 2009 VL 42 IS 3 BP 226 EP 234 DI 10.1016/j.jcomdis.2009.01.001 PG 9 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 434UX UT WOS:000265300700005 PM 19233383 ER PT J AU Flores, AM Jeffery, DD Miller, BA AF Flores, Ann Marie Jeffery, Diana D. Miller, Barry A. TI US Latino Population Composition Change and Comprehensive Cancer Centers SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Hispanics; Latinos; demography; population distribution; analysis; demographic; cancer care facilities; neoplasms ID COLORECTAL-CANCER; PROSTATE-CANCER; DISPARITIES; SURVEILLANCE; SUBGROUPS; QUALITY; VOLUME; CARE AB Background. We describe a typology characterizing population trends of U.S. Latinos/Hispanics from 1990 to 2000 with respect to National Cancer Institute-designated comprehensive cancer centers (CCCs) and corresponding consolidated metropolitan statistical or metropolitan statistical areas (CMSA/MSAs). Methods. Using U.S. Census Bureau data, we constructed population pyramids to analyze population growth and composition for each CMSA/MSA with a CCC. Results. We identified four types of population growth and composition: Type I-Very Fast and Unstable; Type II-Fast and Unstable; Type III-Somewhat Fast and Stable; Type IV-Slow and Stable. Conclusions. The CCCs in areas with Types I and II population growth face the greatest challenges because of the lack of infrastructure for reaching medically underserved Latinos. In contrast, CCCs in areas with Types III and IV population growth may have significant infrastructure but must quickly develop interventions to reach and provide access to aging Latinos to reduce health disparities in cancer mortality and morbidity. C1 [Flores, Ann Marie] Vanderbilt Univ, Dept Orthopaed & Rehabil, Med Ctr, Nashville, TN 37232 USA. [Flores, Ann Marie] Vanderbilt Univ, Sch Nursing, Med Ctr, Nashville, TN 37232 USA. [Jeffery, Diana D.] Natl Canc Inst, Off Canc Survivorship, NIH, Div Canc Control & Populat Sci, Bethesda, MD USA. [Miller, Barry A.] Natl Canc Inst, NIH, Div Canc Control & Populat Sci, Surveillance Res Program,Canc Stat Branch, Bethesda, MD USA. RP Flores, AM (reprint author), Vanderbilt Univ, Dept Orthopaed & Rehabil, Med Ctr, Med Ctr E,South Tower,Suite4460, Nashville, TN 37232 USA. EM ann.m.flores@vanderbilt.edu FU NIMHD NIH HHS [1P20MD000516-01] NR 31 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2009 VL 20 IS 2 BP 346 EP 363 PG 18 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 443CF UT WOS:000265887100005 PM 19395834 ER PT J AU Anwar, S Riazuddin, S Ahmed, ZM Tasneem, S Ateeq-ul-Jaleel Khan, SY Griffith, AJ Friedman, TB Riazuddin, S AF Anwar, Saima Riazuddin, Saima Ahmed, Zubair M. Tasneem, Saba Ateeq-ul-Jaleel Khan, Shahid Y. Griffith, Andrew J. Friedman, Thomas B. Riazuddin, Sheikh TI SLC26A4 mutation spectrum associated with DFNB4 deafness and Pendred's syndrome in Pakistanis SO JOURNAL OF HUMAN GENETICS LA English DT Article DE deafness; DFNB4; Pakistan; Pendred's syndrome; SLC26A4 ID ENLARGED VESTIBULAR AQUEDUCT; NONSYNDROMIC HEARING-LOSS; RECESSIVE DEAFNESS; CFTR GENE; FOUNDER MUTATION; UNIQUE SPECTRUM; PDS GENE; FREQUENCIES; FAMILIES; REARRANGEMENTS AB Pendred's syndrome (PDS) is an autosomal-recessive disorder characterized by sensorineural hearing loss and goiter. PDS is caused by mutations of the SLC26A4 gene encoding pendrin, a transmembrane exchanger of Cl-, I- and HCO3-, which is expressed in the thyroid and inner ear. SLC26A4 mutations can also be associated with non-syndromic deafness, DFNB4. The goal of our study was to define the identities and frequencies of SLC26A4 mutations in 563 large, consanguineous Pakistani families segregating severe-to-profound recessive deafness. Sequence analyses of SLC26A4 in 46 unreported families segregating deafness linked to DFNB4/PDS revealed 16 probable pathogenic variants, 8 of which are novel. The novel variants include three missense substitutions (p.R24L, p.G139V and p.V231M), two splice site mutations (c.304+2T>C and c.1341+3A>C), one frameshift (p.C565MfsX8) and two different genomic deletions affecting exons 1-2 and 11-18. Each of six pathogenic variants (p.V239D, p.Q446R, p.S90L, p.Y556C, p.R24L and p.K715N) was found in more than one family and haplotype analyses suggest that they are founder mutations. Combined with earlier reported data, SLC26A4 mutations were identified in 56 (7.2%; 95% CI: 5.6-9.2%) of 775 families. Therefore, SLC26A4 mutations are the most common known cause of genetic deafness in this population. As p.V239D (30%), p.S90L (18%) and p.Q446R (18%) account for approximately two-third of the mutant alleles of SLC26A4, hierarchical strategies for mutation detection would be feasible and cost-efficient genetic tests for DFNB4 deafness and PDS in Pakistanis. Journal of Human Genetics (2009) 54, 266-270; doi:10.1038/jhg.2009.21; published online 13 March 2009 C1 [Anwar, Saima; Tasneem, Saba; Ateeq-ul-Jaleel; Khan, Shahid Y.; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. [Riazuddin, Saima; Ahmed, Zubair M.; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Sect Human Genet, NIH, Rockville, MD USA. [Griffith, Andrew J.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, NIH, Rockville, MD USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87-W Canal Bank Rd,Thokar Niaz Baig, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Anwar, Saima/C-7477-2016 FU Higher Education Commission (HEC), Islamabad, Pakistan; EMRO/WHOCOMSTECH; Ministry of Science and Technology (MoST), Islamabad, Pakistan; International Center for Genetic Engineering and Biotechnology, Trieste, Italy [02/013]; NIDCD/NIH [1 ZO1 DC000039, 1 ZO1 DC000064] FX We are grateful to the NCEMB families whose participation made this study possible. We thank Byung Yoon Choi, Erich Boger and Imran Shabbir for their technical advice and comments on this paper. This study was supported by the Higher Education Commission (HEC), Islamabad, Pakistan; EMRO/WHOCOMSTECH and Ministry of Science and Technology (MoST), Islamabad, Pakistan; the International Center for Genetic Engineering and Biotechnology, Trieste, Italy under project CRP/PAK02-01 (Contract no. 02/013); and NIDCD/NIH intramural funds 1 ZO1 DC000039 and 1 ZO1 DC000064. NR 36 TC 36 Z9 36 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD MAY PY 2009 VL 54 IS 5 BP 266 EP 270 DI 10.1038/jhg.2009.21 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 452KH UT WOS:000266538400003 PM 19287372 ER PT J AU Pierce, SK Miller, LH AF Pierce, Susan K. Miller, Louis H. TI World Malaria Day 2009: What Malaria Knows about the Immune System That Immunologists Still Do Not SO JOURNAL OF IMMUNOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; BLOOD-STAGE MALARIA; CHONDROITIN SULFATE-A; TUMOR-NECROSIS-FACTOR; ACQUIRED-IMMUNITY; VACCINE DEVELOPMENT; UP-REGULATION; LIVER STAGES; INFECTION AB Malaria kills > 1 million children each year, and there is little doubt that an effective vaccine would play a central role in preventing these deaths. However, the strategies that proved so successful in developing the vaccines we have today may simply not be adequate to confront complex, persistent infectious diseases, including malaria, AIDS, and tuberculosis. We believe that the development of a highly effective vaccine will require a better understanding of several features of the immune response to malaria. At the top of the list is the complex and ancient relationship between the parasite that causes malaria and the immune system that enables the parasite to persist in an otherwise functional immune system. A close second is the antigenic targets in malaria and how to overcome the enormous polymorphism of these targets. Meeting these challenges represents a call to arms of basic immunologists to advance our knowledge of malaria immunity. The Journal of Immunology, 2009,182:5171-5177. C1 [Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Miller, Louis H.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,Mail Stop, Rockville, MD 20852 USA. EM spierce@nih.gov FU Intramural NIH HHS [Z01 AI000949-04] NR 59 TC 46 Z9 50 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2009 VL 182 IS 9 BP 5171 EP 5177 DI 10.4049/jimmunol.0804153 PG 7 WC Immunology SC Immunology GA 563HQ UT WOS:000275119200006 PM 19380759 ER PT J AU Tang, XB Narayanan, S Peruzzi, G Apara, A Natarajan, K Margulies, DH Coligan, JE Borrego, F AF Tang, Xiaobin Narayanan, Sriram Peruzzi, Giovanna Apara, Akintomide Natarajan, Kannan Margulies, David H. Coligan, John E. Borrego, Francisco TI A Single Residue, Arginine 65, Is Critical for the Functional Interaction of Leukocyte-Associated Inhibitory Receptor-1 with Collagens SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IG-LIKE RECEPTOR-1; T-CELLS; ACTIVATION; LAIR-1; DIFFERENTIATION; EXPRESSION; RESPONSES; LIGANDS; COMPLEX; BINDING AB ITIM-containing receptors play an essential role in modulating immune responses. Leukocyte-associated inhibitory receptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all leukocytes, that binds collagens. In this article, we investigate the effect of a conservative R65K mutation on LAIR-1 ligand binding and function. Compared with LAIR-1 wild-type (wt)-expressing cells, LAIR-1 R65K cells show markedly reduced binding to collagen, which correlates with a reduced level of LAIR-1 polarization to the site of interaction with collagens. Both LAIR-1 wt and R65K cells can generate intracellular signals when ligated by anti-LAIR-1 mAb, but only LAIR-1 wt cells respond to collagens or matrigel. In agreement, surface plasmon resonance analyses showed that LAIR-1 R65K protein has markedly reduced avidity for collagen type I compared with LAIR-I wt. Likewise, LAIR-1 R65K protein has decreased avidity for cells expressing transmembrane collagen XVII. Thus, a single residue, Arg65, is critical for the interaction of LAIR-1 with collagens. The Journal of Immunology, 2009, 182: 5446-5452. C1 [Tang, Xiaobin; Narayanan, Sriram; Peruzzi, Giovanna; Apara, Akintomide; Coligan, John E.; Borrego, Francisco] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, Immunol Lab,NIH, Rockville, MD 20852 USA. [Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Rockville, MD 20852 USA. RP Borrego, F (reprint author), US FDA, CDER, Div Monoclonal Antibodies HFD 123, Lab Mol & Dev Immunol, 29 Lincoln Dr,Bldg 29B,Room 3NN18, Bethesda, MD 20892 USA. EM Francisco.Borrego@fda.hhs.gov RI Margulies, David/H-7089-2013; OI Narayanan, Sriram/0000-0002-6484-2800; Margulies, David/0000-0001-8530-7375; Peruzzi, Giovanna/0000-0002-6517-9107 FU National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural program of the National Institute of Allergy and Infectious Diseases. NR 30 TC 17 Z9 18 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2009 VL 182 IS 9 BP 5446 EP 5452 DI 10.4049/jimmunol.0804052 PG 7 WC Immunology SC Immunology GA 563HQ UT WOS:000275119200039 PM 19380792 ER PT J AU Raymond, WW Su, S Makarova, A Wilson, TM Carter, MC Metcalfe, DD Caughey, GH AF Raymond, Wilfred W. Su, Sharon Makarova, Anastasia Wilson, Todd M. Carter, Melody C. Metcalfe, Dean D. Caughey, George H. TI alpha(2)-Macroglobulin Capture Allows Detection of Mast Cell Chymase in Serum and Creates a Reservoir of Angiotensin II-Generating Activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRYPTASE LEVELS; DEPENDENT PATHWAY; CATHEPSIN-G; INHIBITOR; PROTEINASES; MASTOCYTOSIS; ANAPHYLAXIS; CONVERSION; ANGIOGENESIS; ASSOCIATION AB Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by mast cells. When secreted from degranulating cells, it can interact with a variety of circulating antipeptidases, but is mostly captured by alpha(2)-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that alpha(2)-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used alpha(2)-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of similar to 1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. alpha(2)-Macroglobulinbound chymase generates angiotensin 11 in chymase-spiked serum, and it appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin-converting enzyme. These findings suggest that chymase bound to alpha(2)-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that alpha(2)-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases. The Journal of Immunology, 2009, 182: 5770-5777. C1 [Caughey, George H.] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Raymond, Wilfred W.; Caughey, George H.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Caughey, George H.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Su, Sharon] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Makarova, Anastasia; Caughey, George H.] Vet Hlth Res Inst, San Francisco, CA 94121 USA. [Wilson, Todd M.; Carter, Melody C.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. RP Caughey, GH (reprint author), Vet Affairs Med Ctr, 111-D,4150 Clement St, San Francisco, CA 94121 USA. EM george.caughey@ucsf.edu FU National Institutes of Health [HL024136] FX This work was supported in part by National Institutes of Health Grant HL024136. NR 38 TC 17 Z9 18 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2009 VL 182 IS 9 BP 5770 EP 5777 DI 10.4049/jimmunol.0900127 PG 8 WC Immunology SC Immunology GA 563HQ UT WOS:000275119200072 PM 19380825 ER PT J AU Han, TH Jin, P Ren, JQ Slezak, S Marincola, FM Stroncek, DF AF Han, Tae Hee Jin, Ping Ren, Jiaqiang Slezak, Stefanie Marincola, Francesco M. Stroncek, David F. TI Evaluation of 3 Clinical Dendritic Cell Maturation Protocols Containing Lipopolysaccharide and Interferon-gamma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dendritic cells; monocytes; peripheral blood mononuclear cells; interferon-gamma; lipopolysaccharide ID ANTIGEN PRESENTATION; T-CELLS; GENERATION; CANCER; MONOCYTES; IMMUNOTHERAPY; ACTIVATION; PRODUCTS; CAPACITY; IL-12P70 AB Dendritic cells (DCs) are important adjuvants for cancer vaccines. Immature dendritic cells (iDCs) are often produced by the stimulation of peripheral blood monocytes with interleukin (IL)-4 and granulocyte macrophage-colony stimulating factor. For many applications iDCs are treated with cytokines or inflammatory signals to produce mature DCs (mDCs). iDCs are often treated ex vivo with lipopolysaccharide (LPS) and interferon (IFN)-gamma to produce mDCs for clinical therapy. The purpose of this study was to determine if the DC maturation cocktail LPS plus IFN-gamma could be improved by the addition of 2 other DC maturation agents IL-1 beta and tumor necrosis factor (TNF)-alpha. Peripheral blood mononuclear cells were collected from 6 healthy subjects. Monocytes were isolated from the peripheral blood mononuclear cell concentrates by elutriation and were incubated for 3 days with granulocyte macrophage-colony stimulating factor and IL-4 to produce iDCs. iDCs from each subject were divided into 3 and were incubated for 24 hours with LPS plus IFN-gamma; LPS, IFN-gamma, plus IL-1 beta; or LPS, IFN-gamma, IL-1 beta plus TNF-alpha to produce mDCs. The DCs were compared by measuring the expression of costimulator and antigen presenting molecules (CD80, CD83, CD86, and human leukocyte antigen-DR) by flow cytometry, cytokine production (IL-12p70 and IL-10) by enzyme-linked immunosorbent assay and global gene expression using an oligonucleotide microarray. There were no differences in the expression of costimulatory molecules, human leukocyte antigen-DR and CCR7 and production of IL-12p70 among the mDCs produced with the 3 cocktails. Global gene expression analysis found that the expression of 9576 genes differed between the iDCs and mDCs, but the expression of only 13 differed among the 3 different groups of mDCs. There was no benefit of adding IL-1 beta and TNF-alpha to LPS and IFN-alpha to produce mDCs. C1 [Han, Tae Hee; Jin, Ping; Ren, Jiaqiang; Slezak, Stefanie; Marincola, Francesco M.; Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Han, Tae Hee] Inje Univ, Sanggye Paik Hosp, Dept Lab Med, Seoul, South Korea. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711,10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov OI HAN, TAE HEE/0000-0002-9063-4052 FU Intramural NIH HHS [Z01 CL002103-08] NR 30 TC 27 Z9 29 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD MAY PY 2009 VL 32 IS 4 BP 399 EP 407 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 437BL UT WOS:000265460700009 PM 19342965 ER PT J AU Kreimer, AR AF Kreimer, Aimee R. TI Oral Sexual Behaviors and the Prevalence of Oral Human Papillomavirus Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID PARTICLE VACCINE; EFFICACY; CANCER; TRIAL; TYPE-18; TRENDS; HEAD C1 [Kreimer, Aimee R.] NCI, NIH, Bethesda, MD 20892 USA. RP Kreimer, AR (reprint author), 6120 Execut Blvd,EPS 7084, Rockville, MD 20852 USA. EM kreimera@mail.nih.gov RI Kreimer, Aimee/H-1687-2015 NR 15 TC 6 Z9 7 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2009 VL 199 IS 9 BP 1253 EP 1254 DI 10.1086/597756 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 431BE UT WOS:000265035500001 PM 19320591 ER PT J AU Wind-Rotolo, M Durand, C Cranmer, L Reid, A Martinson, N Doherty, M Jilek, BL Kagaayi, J Kizza, A Pillay, V Laeyendecker, O Reynolds, SJ Eshleman, SH Lau, B Ray, SC Siliciano, JD Quinn, TC Siliciano, RF AF Wind-Rotolo, Megan Durand, Christine Cranmer, Lisa Reid, Alison Martinson, Neil Doherty, Meg Jilek, Benjamin L. Kagaayi, Joseph Kizza, Allan Pillay, Visva Laeyendecker, Oliver Reynolds, Steven J. Eshleman, Susan H. Lau, Bryan Ray, Stuart C. Siliciano, Janet D. Quinn, Thomas C. Siliciano, Robert F. TI Identification of Nevirapine-Resistant HIV-1 in the Latent Reservoir after Single-Dose Nevirapine to Prevent Mother-to-Child Transmission of HIV-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 15th Conference on Retroviruses and Opportunistic Infections CY FEB 03-06, 2008 CL Boston, MA ID IMMUNODEFICIENCY-VIRUS TYPE-1; VERTICAL TRANSMISSION; SUBTYPE-A; ANTIRETROVIRAL THERAPY; RANDOMIZED-TRIAL; QUANTITATIVE-ANALYSIS; RECEIVING NEVIRAPINE; FOLLOW-UP; WOMEN; PERSISTENCE AB Background. Intrapartum single-dose nevirapine decreases mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but promotes nevirapine resistance. Although resistant viruses fade to undetectable levels in plasma, they may persist as stably integrated proviruses within the latent reservoir in resting CD4(+) T cells, potentially complicating future treatment. Methods. Blood samples were collected from 60 women from South Africa and Uganda >6 months after they had received single-dose nevirapine. To selectively analyze the stable latent form of HIV-1, resting CD4(+) T cells were isolated and activated in the presence of reverse-transcriptase inhibitors and integrase inhibitors, which allows for the specific isolation of viruses produced by cells with stably integrated proviral DNA. These viruses were then analyzed for nevirapine resistance. Results. Although only a small number of latently infected cells were present in each blood sample (mean, 162 cells), nevirapine resistance mutations (K103N and G190A) were detected in the latent reservoir of 4 (8%) of 50 evaluable women. Conclusions. A single dose of nevirapine can establish antiretroviral resistance within the latent reservoir. This results in a potentially lifelong risk of reemergence of nevirapine-resistant virus and highlights the need for strategies to prevent transmission that do not compromise successful future treatment. C1 [Wind-Rotolo, Megan; Durand, Christine; Cranmer, Lisa; Reid, Alison; Martinson, Neil; Doherty, Meg; Jilek, Benjamin L.; Laeyendecker, Oliver; Reynolds, Steven J.; Lau, Bryan; Ray, Stuart C.; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Laeyendecker, Oliver; Reynolds, Steven J.; Quinn, Thomas C.] NIAID, NIH, Baltimore, MD USA. [Siliciano, Robert F.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. [Martinson, Neil] Univ Witwatersrand, Perinatal HIV Res Unit, Soweto, South Africa. [Pillay, Visva] Natl Inst Communicable Dis, Johannesburg, South Africa. [Kagaayi, Joseph; Kizza, Allan] Rakai Hlth Sci Program, Rakai, Uganda. RP Wind-Rotolo, M (reprint author), POB 4000, Princeton, NJ 08543 USA. EM mwrotolo@gmail.com RI Laeyendecker, Oliver/B-9331-2009; Ray, Stuart/B-7527-2008; Pillay, Viness/C-1569-2010; OI Ray, Stuart/0000-0002-1051-7260; Laeyendecker, Oliver/0000-0002-6429-4760 FU Howard Hughes Medical Institute; Intramural NIH HHS [Z01 AI000361-25, Z99 AI999999]; NIAID NIH HHS [U01 AI068613-03, AI43222, K01 AI071754, K01-AI071754, R01 AI043222, U01 AI046745, U01 AI046745-01, U01 AI046745-02, U01 AI048054, U01 AI068613, U01 AI068632, U01-AI-068613, U01-AI-068632, U01-AI-46745, U01-AI-48054] NR 35 TC 27 Z9 27 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2009 VL 199 IS 9 BP 1301 EP 1309 DI 10.1086/597759 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 431BE UT WOS:000265035500010 PM 19338474 ER PT J AU Morens, DM Taubenberger, JK Fauci, AS AF Morens, David M. Taubenberger, Jeffery K. Fauci, Anthony S. TI Was Bacterial Pneumonia the Predominant Cause of Death in the 1918-1919 Influenza Pandemic? Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Morens, David M.; Taubenberger, Jeffery K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, Bldg 31,Rm 7A-03,31 Ctr Dr, Bethesda, MD 20892 USA. EM dm270q@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2009 VL 199 IS 9 BP 1409 EP 1410 DI 10.1086/597623 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 431BE UT WOS:000265035500026 ER PT J AU Ciencewicki, JM Brighton, LE Jaspers, I AF Ciencewicki, Jonathan M. Brighton, Luisa E. Jaspers, Ilona TI Localization of Type I Interferon Receptor Limits Interferon-Induced TLR3 in Epithelial Cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; INFLUENZA-A-VIRUS; GENE-EXPRESSION; IMMUNE-RESPONSE; KAPPA-B; AIRWAY EPITHELIUM; TIGHT JUNCTION; IFN-ALPHA; ACTIVATION AB Previous studies have shown that influenza infections increase Toll-like receptor 3 (TLR3) expression and that type I interferons (IFNs) may play a role in this response. This study aimed to expand on the role of type I IFNs in the influenza-induced upregulation of TLR3 and determine whether and how the localization of the IFN-alpha/beta receptor (IFNAR) in respiratory epithelial cells could modify IFN-induced responses. Using differentiated primary human airway epithelial cells this study demonstrates that soluble mediators secreted in response to influenza infection upregulate TLR3 expression in naive cells. This response was associated with an upregulation of type I IFNs and stimulation with type I, but not type II, IFNs enhanced TLR3 expression. Interestingly, although influenza infection results in IFN-beta release both toward the apical and basolateral sides of the epithelium, TLR3 expression is only enhanced in cells stimulated with IFN-beta from the basolateral side. Immunohistochemical analysis demonstrates that IFNAR expression is limited to the basolateral side of differentiated human airway epithelial cells. However, non- or poorly differentiated epithelial cells express IFNAR more toward the apical side. These data demonstrate that restricted expression of the IFNAR in the differentiated airway epithelium presents a potential mechanism of regulating type I IFN-induced TLR3 expression. C1 [Brighton, Luisa E.; Jaspers, Ilona] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC 27599 USA. [Jaspers, Ilona] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. [Ciencewicki, Jonathan M.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Jaspers, I (reprint author), Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, 104 Mason Farm Rd,CB 7310, Chapel Hill, NC 27599 USA. EM ilona_jaspers@med.unc.edu FU National Institute of Environmental Health Sciences (NIEHS) [ES013611]; National Institutes of Health (NIH); Environmental Protection Agency (EPA) [CR829522]; EPA-UNC Curriculum in Toxicology Training agreement [T829472] FX We thank Wenli Zhang for her technical assistance, and Robert Silbajoris for his help with the real-time RT-PCR. We also thank Drs Devlin and Ross and Ms Dailey for help with the epithelial differentiation time course. The project described was supported by grant number ES013611 from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), as well as a grant from the Environmental Protection Agency (EPA) (CR829522) (all I.J.) and, finally, the EPA-UNC Curriculum in Toxicology Training agreement (No. T829472). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH. Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through cooperative agreement CR829522 with the Center for Environmental Medicine, Asthma, and Lung Biology, it has not been subjected to the Agency's required peer and policy review and, therefore, does not necessarily reflect the views of the Agency, and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. NR 39 TC 15 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD MAY PY 2009 VL 29 IS 5 BP 289 EP 297 DI 10.1089/jir.2008.0075 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 441QF UT WOS:000265783200005 PM 19231996 ER PT J AU Wu, XS Lonsdorf, AS Hwang, ST AF Wu, Xue-Song Lonsdorf, Anke S. Hwang, Sam T. TI Cutaneous T-Cell Lymphoma: Roles for Chemokines and Chemokine Receptors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review ID ACTIVATION-REGULATED CHEMOKINE; MYCOSIS-FUNGOIDES; DENDRITIC CELLS; SEZARY-SYNDROME; CUTTING EDGE; EXPRESSION; SKIN; CCR4; IMMUNOTHERAPY; INFLAMMATION AB Chemokine receptors are G-protein-coupled, seven-transmembrane-spanning surface receptors that play key roles in cell trafficking, cell motility, and survival. These receptors are activated by small molecular weight chemotactic cytokines called chemokines. Chemokine receptors play roles in the migration and localization of normal T cells (and other leukocytes) during physiological responses in inflamed or infected skin. In cancer cells, these receptors may also facilitate tumorigenesis, metastasis, and resistance to immune-mediated killing. This review will focus on recent data that reveal potential roles of specific chemokine receptors, including CCR4, CXCR4, and CCR10, in the pathophysiology of cutaneous T-cell lymphoma, including mycosis fungoides and Sezary syndrome. C1 [Wu, Xue-Song; Lonsdorf, Anke S.; Hwang, Sam T.] NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Ctr Canc Res, Bldg 10 Rm 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov FU NIH-German Research Foundation (DFG) FX Anke S. Lonsdorf is a recipient of an NIH-German Research Foundation (DFG) Career Transition Award. NR 36 TC 32 Z9 33 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2009 VL 129 IS 5 BP 1115 EP 1119 DI 10.1038/jid.2009.45 PG 5 WC Dermatology SC Dermatology GA 447US UT WOS:000266218000010 PM 19242508 ER PT J AU Klaschik, S Tross, D Klinman, DM AF Klaschik, Sven Tross, Debra Klinman, Dennis M. TI Inductive and suppressive networks regulate TLR9-dependent gene expression in vivo SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE rodent; gene regulation; signal transduction; molecular biology ID NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; BACTERIAL CPG-DNA; CELL-ACTIVATION; CUTTING EDGE; INTERFERON-GAMMA; T-CELLS; PHASE-I; OLIGODEOXYNUCLEOTIDES; MURINE AB Bacterial DNA expressing unmethylated CpG motifs binds to TLR9, thereby stimulating a broadly protective, innate immune response. Although CpG-mediated signal transduction has been studied, the scope of TLR9-dependent gene expression is incompletely understood. To resolve these issues, mice were treated with immunostimulatory CpG oligonucleotides (ODN) and splenic mRNA levels monitored from 30 min through 3 days by microarray. Through the unique application of bioinformatic analysis to these experimental data, this study is the first to describe the complex regulatory networks responsible for TLR9-mediated gene expression. Current results are the first to establish that CpG-induced stimulation of the innate immune system proceeds in multiple waves over time, and gene up-regulation is mediated by a small number of temporally activated "major inducers" and "minor inducers". An additional study of TNF knockout mice supports the conclusion that the regulatory networks identified by our bioinformatic analysis accurately identified CpG ODN-driven gene-gene interactions in vivo. Equally important, this work identifies the counter-regulatory mechanisms embedded within the signaling cascade that suppresses the proinflammatory response triggered in vivo by CpG DNA stimulation. Identifying these network interactions provides novel and global insights into the regulation of TLR9-mediated gene activation, improves our understanding of TLR-mediated host defense, and facilitates the development of interventions designed to optimize the nature and duration of the ensuing response. J. Leukoc. Biol. 85: 788-795; 2009. C1 [Klaschik, Sven; Tross, Debra; Klinman, Dennis M.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Bldg 567,Room 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 51 TC 27 Z9 27 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY 1 PY 2009 VL 85 IS 5 BP 788 EP 795 DI 10.1189/jlb.1008671 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 453TM UT WOS:000266635800006 PM 19179452 ER PT J AU Immenschuh, S Naidu, S Chavakis, T Beschmann, H Ludwig, RJ Santoso, S AF Immenschuh, Stephan Naidu, Srivatsava Chavakis, Triantafyllos Beschmann, Heike Ludwig, Ralf J. Santoso, Sentot TI Transcriptional induction of junctional adhesion molecule-C gene expression in activated T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE T lymphocytes; gene regulation; cell activation ID HEME OXYGENASE-1 GENE; JAM-C; TRANSENDOTHELIAL MIGRATION; IN-VIVO; FAMILY; PROTEINS; TRANSMIGRATION; IDENTIFICATION; PLATELETS; INTEGRIN AB Junctional adhesion molecule (JAM)-C is an Ig superfamily protein, which is involved in the regulation of various inflammatory and vascular events such as transendothelial leukocyte migration. JAM-C is expressed highly on the surface of endothelial cells and platelets, whereas expression in T lymphocytes is not well studied. To investigate the specific gene regulation of JAM-C in T lymphocytes, we determined JAM-C expression in quiescent and activated human T cells. Treatment with the polyclonal T cell activator PHA increased surface and total JAM-C expression in T cells time- and dose-dependently, as determined by flow cytometry and immunoblot analysis. In contrast, no up-regulation of JAM-A in activated T cells was detectable. The highest level of JAM-C up-regulation by PHA was observed in CD3(+) forkhead box P3(+) and CD4(+) CD25(high) T cells. Moreover, TCR activation with combined anti-CD3 and anti-CD28 stimulation induced JAM-C expression in T cells. JAM-C induction occurred at the mRNA level, suggesting a transcriptional regulatory mechanism of JAM-C expression. Accordingly, we studied the regulation of the human JAM-C gene promoter in transiently transfected T cells. Luciferase activity of a JAM-C promoter gene construct with three potential consensus sites for the transcription factor NFAT was induced markedly in activated T cells. Finally, pretreatment with two pharmacological inhibitors of calcineurin, cyclosporin A, and FK-506, but not with MAPK inhibitors, blocked JAM-C induction in activated T cells. In summary, JAM-C is up-regulated in activated human T lymphocytes via a transcriptional mechanism, suggesting a potential role of JAM-C in T cell functions. J. Leukoc. Biol. 85: 796-803; 2009. C1 [Immenschuh, Stephan; Naidu, Srivatsava; Santoso, Sentot] Univ Giessen, Inst Clin Immunol & Transfus Med, D-6300 Giessen, Germany. [Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Beschmann, Heike; Ludwig, Ralf J.] Univ Frankfurt, Dept Dermatol, Frankfurt, Germany. [Ludwig, Ralf J.] Med Univ Lubeck, Dept Dermatol, D-23538 Lubeck, Germany. RP Immenschuh, S (reprint author), Hannover Med Sch, Inst Transfus Med, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM stephan@mh-hannover.de RI Ludwig, Ralf/A-2629-2008 OI Ludwig, Ralf/0000-0002-1394-1737 FU Deutsche Forschungsgemeinschaft [SFB 547] FX This work was supported by a grant from the Deutsche Forschungsgemeinschaft SFB 547 ( S. I. and S. S.). We thank R. Bohnel, S. Werth, and A. Zeyer for excellent technical assistance. We also thank Dr. James A. Goodrich for the supply of the plasmid pGL3-NFAT3. NR 34 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY 1 PY 2009 VL 85 IS 5 BP 796 EP 803 DI 10.1189/jlb.0708422 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 453TM UT WOS:000266635800007 PM 19204148 ER PT J AU Henry, SC Daniell, XG Burroughs, AR Indaram, M Howell, DN Coers, R Starnbach, MN Hunn, JP Howard, JC Feng, CG Sher, A Taylor, GA AF Henry, Stanley C. Daniell, Xiaoju G. Burroughs, Ashley R. Indaram, Maanasa Howell, David N. Coers, Joern Starnbach, Michael N. Hunn, Julia P. Howard, Jonathan C. Feng, Carl G. Sher, Alan Taylor, Gregory A. TI Balance of Irgm protein activities determines IFN-gamma-induced host defense SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE interferon; resistance; p47 GTPases ID INDUCIBLY EXPRESSED GTPASE; TOXOPLASMA-GONDII; INTRACELLULAR PATHOGENS; P47 GTPASES; SALMONELLA-TYPHIMURIUM; ENDOPLASMIC-RETICULUM; RESISTANCE GTPASES; INTERFERON-GAMMA; IMMUNE CONTROL; MICE LACKING AB The immunity-related GTPases (IRG), also known as p47 GTPases, are a family of proteins that are tightly regulated by IFNs at the transcriptional level and serve as key mediators of IFN-regulated resistance to intracellular bacteria and protozoa. Among the IRG proteins, loss of Irgm1 has the most profound impact on IFN-gamma-induced host resistance at the physiological level. Surprisingly, the losses of host resistance seen in the absence of Irgm1 are sometimes more striking than those seen in the absence of IFN-gamma. In the current work, we address the underlying mechanism. We find that in several contexts, another protein in the IRG family, Irgm3, functions to counter the effects of Irgm1. By creating mice that lack Irgm1 and Irgm3, we show that several phenotypes important to host resistance that are caused by Irgm1 deficiency are reversed by coincident Irgm3 deficiency; these include resistance to Salmonella typhimurium in vivo, the ability to affect IFN-gamma-induced Salmonella killing in isolated macrophages, and the ability to regulate macrophage adhesion and motility in vitro. Other phenotypes that are caused by Irgm1 deficiency, including susceptibility to Toxoplasma gondii and the regulation of GKS IRG protein expression and localization, are not reversed but exacerbated when Irgm3 is also absent. These data suggest that members of the Irgm subfamily within the larger IRG family possess activities that can be opposing or cooperative depending on the context, and it is the balance of these activities that is pivotal in mediating IFN-gamma-regulated host resistance. J. Leukoc. Biol. 85: 877-885; 2009. C1 [Henry, Stanley C.; Taylor, Gregory A.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. [Daniell, Xiaoju G.; Burroughs, Ashley R.; Indaram, Maanasa; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Med, Div Geriatr, Durham, NC 27710 USA. [Daniell, Xiaoju G.; Burroughs, Ashley R.; Indaram, Maanasa; Taylor, Gregory A.] Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. [Daniell, Xiaoju G.; Burroughs, Ashley R.; Indaram, Maanasa; Taylor, Gregory A.] Duke Univ, Med Ctr, Div Geriatr, Dept Mol Genet, Durham, NC USA. [Daniell, Xiaoju G.; Burroughs, Ashley R.; Indaram, Maanasa; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Microbiol & Immunol, Div Geriatr, Durham, NC 27710 USA. [Howell, David N.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. [Coers, Joern; Starnbach, Michael N.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Hunn, Julia P.; Howard, Jonathan C.] Univ Cologne, Inst Genet, D-5000 Cologne, Germany. [Feng, Carl G.; Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Taylor, GA (reprint author), Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 508 Fulton St,Room N3008, Durham, NC 27705 USA. EM gregory.taylor@duke.edu OI Howard, Jonathan/0000-0003-2756-5143 FU National Institutes of Health [AI57831]; VA Merit Review; Charles A. King Trust Postdoctoral Research fellowship FX This work was supported by a National Institutes of Health grant ( AI57831; to G. A. T.), a VA Merit Review grant ( to G. A. T.), and a Charles A. King Trust Postdoctoral Research fellowship ( to J. C). We thank Vojo Deretic, Sudha Singh, and Brice Weinberg for helpful discussions. NR 31 TC 40 Z9 42 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY 1 PY 2009 VL 85 IS 5 BP 877 EP 885 DI 10.1189/jlb.1008599 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 453TM UT WOS:000266635800016 PM 19176402 ER PT J AU Cho, JY Kang, DW Ma, XC Ahn, SH Krausz, KW Luecke, H Idle, JR Gonzalez, FJ AF Cho, Joo-Youn Kang, Dong Wook Ma, Xiaochao Ahn, Sung-Hoon Krausz, Kristopher W. Luecke, Hans Idle, Jeffrey R. Gonzalez, Frank J. TI Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE pregnane X receptor; pregnenolone 16 alpha-carbonitrile; carboxyethyl hydroxychroman; metabolomics; gamma-CEHC glucoside; sterol carrier protein 2; peroxisomal beta-oxidation ID PREGNANE-X-RECEPTOR; STEROL CARRIER PROTEIN-2; NUCLEAR RECEPTORS; ALPHA-TOCOPHEROL; CROSS-TALK; XENOBIOTIC RESPONSE; LIPID-METABOLISM; ACID-METABOLISM; GENE; CAR AB Pregnane X receptor (PXR) is an important nuclear receptor xenosensor that regulates the expression of metabolic enzymes and transporters involved in the metabolism of xenobiotics and endobiotics. In this study, ultra-performance liquid chromatography (UPLC) coupled with electrospray time-of-flight mass spectrometry (TOFMS), revealed altered urinary metabolomes in both Pxr-null and wild-type mice treated with the mouse PXR activator pregnenolone 16 alpha-carbonitrile (PCN). Multivariate data analysis revealed that PCN significantly attenuated the urinary vitamin E metabolite alpha-carboxyethyl hydroxychroman (CEHC) glucuronide together with a novel metabolite in wild-type but not Pxr-null mice. Deconjugation experiments with beta-glucuronidase and beta-glucosidase suggested that the novel urinary metabolite was gamma-CEHC beta-D-glucoside (Glc). The identity of gamma-CEHC Glc was confirmed by chemical synthesis and by comparing tandem mass fragmentation of the urinary metabolite with the authentic standard. The lower urinary CEHC was likely due to PXR-mediated repression of hepatic sterol carrier protein 2 involved in peroxisomal beta-oxidation of branched-chain fatty acids (BCFA). Using a combination of metabolomic analysis and a genetically modified mouse model, this study revealed that activation of PXR results in attenuated levels of the two vitamin E conjugates, and identification of a novel vitamin E metabolite, gamma-CEHC Glc. jlr Activation of PXR results in attenuated levels of the two vitamin E conjugates that may be useful as biomarkers of PXR activation.-Cho, J-Y., D. W. Kang, X. Ma, S-H. Ahn, K. W. Krausz, H. Luecke, J. R. Idle, and F. J. Gonzalez. Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation. J. Lipid Res. 2009. 50: 924-937. C1 [Cho, Joo-Youn; Ma, Xiaochao; Ahn, Sung-Hoon; Krausz, Kristopher W.; Idle, Jeffrey R.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kang, Dong Wook; Luecke, Hans] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Idle, Jeffrey R.] Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague 12800 2, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Cho, Joo-Youn/J-5672-2012; OI Idle, Jeff/0000-0002-6143-1520 NR 46 TC 27 Z9 27 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 2009 VL 50 IS 5 BP 924 EP 937 DI 10.1194/jlr.M800647-JLR200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 430DP UT WOS:000264969300017 PM 19141872 ER PT J AU Shemesh, N Ozarslan, E Basser, PJ Cohen, Y AF Shemesh, Noam Ozarslan, Evren Basser, Peter J. Cohen, Yoram TI Measuring small compartmental dimensions with low-q angular double-PGSE NMR: The effect of experimental parameters on signal decay SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Pulsed field gradient; Spin echo; Double PGSE; d-PGSE; Diffusion; White matter; Phantom; Low-q; PFG; Diffusion NMR; Double-pulsed gradient spin echo ID GRADIENT SPIN-ECHO; STRUCTURAL INFORMATION; FIELD-GRADIENT; SPHERICAL PORES; POROUS-MEDIA; DIFFUSION-DIFFRACTION; RESTRICTED DIFFUSION; FOURIER-TRANSFORM; ROTATIONAL ANGLE; BRAIN-TISSUE AB In confined geometries, the MR signal attenuation obtained from single pulsed gradient spin echo (s-PGSE) experiments reflects the dimension of the compartment, and in some cases, its geometry. However, to measure compartment size, high q-values must be applied, requiring high gradient: strengths and/or long pulse durations and diffusion times. The angular double PGSE (d-PGSE) experiment has been proposed as a means to extract dimensions of confined geometries using low q-values. In one realization of the d-PGSE experiment, the first gradient pair is fixed along the x-axis, and the orientation of the second gradient pair is varied in the X-Y plane. Such a measurement is sensitive to microscopic anisotropy induced by the boundaries of the restricting compartment, and allows extraction of the compartment dimension. In this study, we have juxtaposed angular d-PGSE experiments and simulations to extract sizes from well-characterized NMR phantoms consisting of water filled microcapillaries. We are able to accurately extract sizes of small compartments (5 mu m) using the angular d-PGSE experiment even when the short gradient pulse (SGP) approximation is violated and over a range of mixing and diffusion times. We conclude that the angular d-PGSE experiment may fill an important niche in characterizing compartment sizes in which restricted diffusion occurs. (C) 2009 Elsevier Inc. All rights reserved. C1 [Shemesh, Noam; Cohen, Yoram] Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. [Ozarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD USA. RP Cohen, Y (reprint author), Tel Aviv Univ, Sch Chem, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM ycohen@post.tau.ac.il RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011; OI Ozarslan, Evren/0000-0003-0859-1311; Shemesh, Noam/0000-0001-6681-5876 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX PJ.B and E.O were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 43 TC 44 Z9 44 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2009 VL 198 IS 1 BP 15 EP 23 DI 10.1016/j.jmr.2009.01.004 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 433UU UT WOS:000265232100003 PM 19186086 ER PT J AU Hu, SW Olulade, O Tamer, GG Luh, WM Talavage, TM AF Hu, Shuowen Olulade, Olumide Tamer, Gregory G., Jr. Luh, Wen-Ming Talavage, Thomas M. TI Signal Fluctuations Induced by Non-T-1-Related Confounds in Variable TR fMRI Experiments SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE variable TR; non-T-1-related artifacts; eddy currents; gradient coil heating ID EVENT-RELATED FMRI; AUDITORY-CORTEX; ACOUSTIC NOISE; RESPONSES AB Purpose: To assess and model signal fluctuations induced by non-T-1-related confounds in variable repetition time (TR) functional magnetic resonance imaging (fMRI) and to develop a compensation procedure to correct for the non-T-1-related artifacts. Materials and Methods: Radiofrequency disabled volume gradient sequences were effected at variable offsets between actual image acquisitions, enabling perturbation of the measurement system without perturbing longitudinal magnetization, allowing the study of non-T-1-related confounds that may arise in variable TR experiments. Three imaging sessions utilizing a daily quality assurance (DQA) phantom were conducted to assess the signal fluctuations, which were then modeled as a second-order system. A modified projection procedure was implemented to correct for signal fluctuations arising from non-T-1-related confounds, and statistical analysis was performed to assess the significance of the artifacts with and without compensation. Results: Assessment using phantom data reveals that the signal fluctuations induced by non-T-1-related confounds was consistent in shape across the phantom and well-modeled by a second-order system. The phantom exhibited significant spurious detections (at P < 0.01) almost uniformly across the central slices of the phantom. Conclusion: Second-order system modeling and compensation of non-T-1-related confounds achieves significant reduction of spurious detection of fMRI activity in a phantom. C1 [Luh, Wen-Ming] NIH, Bethesda, MD 20892 USA. [Tamer, Gregory G., Jr.; Talavage, Thomas M.] Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA. [Hu, Shuowen; Olulade, Olumide; Talavage, Thomas M.] Purdue Univ, Sch Elect & Comp Engn, W Lafayette, IN 47907 USA. RP Hu, SW (reprint author), 465 Northwestern Ave, W Lafayette, IN 47906 USA. EM hu@ecn.purdue.edu FU National Institutes of Health (NIH) [R01EB003990] FX National Institutes of Health (NIH): Contract grant number: R01EB003990. NR 14 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD MAY PY 2009 VL 29 IS 5 BP 1234 EP 1239 DI 10.1002/jmri.21767 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 439IQ UT WOS:000265621200033 PM 19388103 ER PT J AU Vaisbuch, E Kusanovici, JP Erez, O Mazaki-Tovi, S Gotsch, F Kim, CJ Kim, JS Chaiworapongsa, T Edwin, S Than, NG Nhan-Chang, CL Mazor, M Mittal, P Hassan, SS Romero, R AF Vaisbuch, Edi Kusanovici, Juan Pedro Erez, Offer Mazaki-Tovi, Shali Gotsch, Francesca Kim, Chong Jai Kim, Jung-Sun Chaiworapongsa, Tinnakorn Edwin, Sam Than, Nandor Gabor Nhan-Chang, Chia-Ling Mazor, Moshe Mittal, Pooja Hassan, Sonia S. Romero, Roberto TI Amniotic fluid fetal hemoglobin in normal pregnancies and pregnancies complicated with preterm labor or prelabor rupture of membranes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Hemoglobin; fetus; preterm delivery; PPROM; pregnancy; amniocentesis; intra-amniotic infection/inflammation ID INTRAAMNIOTIC MATERNAL HEMORRHAGE; ECHOGENIC BOWEL; AMNIOCENTESIS; CIRCUMVALLATE; INFECTION; PLACENTA; DEFENSE; SYSTEMS; BLOOD; IRON AB Objective. Hemoglobin and its catabolic products have been associated with amniotic fluid (AF) discoloration and intra-amniotic infection/inflammation (IAI). However, the origin of AF hemoglobin (maternal or fetal) has not been determined. The aims of this study were to determine if fetal hemoglobin can be detected in AF obtained from normal pregnancies, and whether there is an association between AF fetal hemoglobin concentrations and gestational age, spontaneous labor (term and preterm), preterm prelabor rupture of membranes (PPROM) and IAI. Study design. This cross-sectional study included pregnant women in the following groups: (1) mid-trimester (n = 60); (2) term not in labor (n = 21); (3) term in labor (n = 47); (4) spontaneous preterm labor with intact membranes (PTL) without IAI who delivered at term (n = 89); (5) PTL without IAI who delivered preterm (n = 74); (6) PTL with IAI (n = 78); (7) PPROM with (n = 48) and (8) without IAI (n = 48). AF fetal hemoglobin concentrations were determined by ELISA. Nonparametric statistics were used for analyses. Results. (1) Fetal hemoglobin was detected in 80.4% of all AF samples; (2) women at term not in labor had a higher median AF fetal hemoglobin concentration than those at mid-trimester (p = 0.008); (3) labor at term was not associated with a significant difference in the median AF fetal hemoglobin concentration; (4) the median AF fetal hemoglobin concentration was not significantly different among the three PTL groups or between the PPROM groups; (5) women with PTL and IAI had a lower AF fetal hemoglobin percentage of the total hemoglobin than those without IAI who delivered preterm (p = 0.03) or at term (p < 0.001); (6) The median AF fetal hemoglobin concentration was higher in pregnancies complicated with PTL or PPROM than in women at term (p < 0.001 for all comparison). Conclusions. (1) The concentration of immunoreactive AF fetal hemoglobin increases with gestational age; (2) the median AF fetal hemoglobin concentration is higher in pregnancies complicated with PTL or PPROM than in term pregnancies; (3) among women with PTL or PPROM, the AF fetal hemoglobin concentrations were not associated with IAI; (4) however, women with PTL and IAI had a lower percentage of AF fetal hemoglobin of the total hemoglobin than those without IAI, suggesting different mechanisms of disease. C1 [Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mazaki-Tovi, Shali; Gotsch, Francesca; Kim, Chong Jai; Kim, Jung-Sun; Chaiworapongsa, Tinnakorn; Edwin, Sam; Than, Nandor Gabor; Nhan-Chang, Chia-Ling; Mittal, Pooja; Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NICHD, NIH,DHHS, Bethesda, MD USA. [Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mazaki-Tovi, Shali; Gotsch, Francesca; Kim, Chong Jai; Kim, Jung-Sun; Chaiworapongsa, Tinnakorn; Edwin, Sam; Than, Nandor Gabor; Nhan-Chang, Chia-Ling; Mittal, Pooja; Hassan, Sonia S.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI USA. [Vaisbuch, Edi; Kusanovici, Juan Pedro; Erez, Offer; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Mittal, Pooja; Hassan, Sonia S.] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA. [Kim, Chong Jai; Kim, Jung-Sun] Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48201 USA. [Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, IL-84105 Beer Sheva, Israel. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,Box 4, Detroit, MI 48201 USA. EM evaisbuch@med.wayne.edu; prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 34 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2009 VL 22 IS 5 BP 388 EP 397 DI 10.1080/14767050802578285 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 473YP UT WOS:000268248800003 PM 19529995 ER PT J AU Esona, MD Geyer, A Page, N Trabelsi, A Fodha, I Aminu, M Agbaya, VA Tsion, B Kerin, TK Armah, GE Steele, AD Glass, RI Gentsch, JR AF Esona, M. D. Geyer, A. Page, N. Trabelsi, A. Fodha, I. Aminu, M. Agbaya, V. A. Tsion, B. Kerin, T. K. Armah, G. E. Steele, A. D. Glass, R. I. Gentsch, J. R. TI Genomic Characterization of Human Rotavirus G8 Strains From the African Rotavirus Network: Relationship to Animal Rotaviruses SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE rotavirus; characterization; classification; evolution; reassortment ID GROUP-A ROTAVIRUS; RNA-RNA HYBRIDIZATION; AMINO-ACID-SEQUENCE; POLYMERASE CHAIN-REACTION; PORCINE ROTAVIRUS; MONOCLONAL-ANTIBODIES; NONSTRUCTURAL PROTEIN; UNITED-KINGDOM; MOLECULAR CHARACTERIZATION; INTERSPECIES TRANSMISSION AB Global rotavirus surveillance has led to the detection of many unusual human rotavirus (HRV) genotypes. During 1996-2004 surveillance within the African Rotavirus Network (ARN), six P[8],G8 and two P[6],G8 human rotavirus strains were identified. Gene fragments (RT-PCR amplicons) of all 11-gene segments of these G8 strains were sequenced in order to elucidate their genetic and evolutionary relationships. Phylogenetic and sequence analyses of each gene segment revealed high similarities (88-100% nt and 91-100% aa) for all segments except for gene 4 encoding VP4 proteins P[8] and P[6]. For most strains, almost all of the genes of the ARN strains other than neutralizing antigens are related to typical human strains of Wa genogroup. The VP7, NSP2, and NSP5 genes were closely related to cognate genes of animal strains (83-99% and 97-99% aa identity). This study suggests that the ARN G8 strains might have arisen through VP7 or VP4 gene reassortment events since most of the other gene segments resemble those of common human rotaviruses. However, VP7, NSP2 (likely), and NSP5 (likely) genes are derived potentially from animals consistent with a zoonotic introduction. Although these findings help elucidate rotavirus evolution, sequence studies of cognate animal rotavirus genes are needed to conclusively determine the specific origin of those genes relative to both human and animal rotavirus strains. J. Med. Virol. 81:937-951, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Esona, M. D.; Kerin, T. K.; Gentsch, J. R.] CDC, NCIRD, Div Viral Dis, Gastroenteritis & Resp Viruses Lab Branch, Atlanta, GA 30333 USA. [Page, N.] Natl Inst Communicable Dis, Viral Gastroenteritis Unit, Johannesburg, South Africa. [Trabelsi, A.; Fodha, I.] Univ Hosp Sahloul, Lab Bacteriol Virol, Sousse, Tunisia. [Aminu, M.] Ahmadu Bello Univ, Dept Microbiol, Zaria, Nigeria. [Agbaya, V. A.] Inst Pasteur Cote dIvoire DVE, Lab Bacteriol Virol, Abidjan, Cote Ivoire. [Tsion, B.] Ethiopian Inst Virol, Addis Ababa, Ethiopia. [Armah, G. E.] Noguchi Mem Res Inst, Accra, Ghana. [Steele, A. D.] NW, PATH, Seattle, WA USA. [Glass, R. I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Geyer, A.] Univ Limpopo, MRC, DPRU, Limpopo, South Africa. RP Esona, MD (reprint author), 1600 Clifton Rd,NE,Mail Stop G-04, Atlanta, GA 30333 USA. EM mdi4@cdc.gov OI Page, Nicola/0000-0001-5845-4417 NR 93 TC 59 Z9 59 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 2009 VL 81 IS 5 BP 937 EP 951 DI 10.1002/jmv.21468 PG 15 WC Virology SC Virology GA 429FR UT WOS:000264906800023 PM 19319943 ER PT J AU Wan, XH Tuckerman, JR Saito, JA Freitas, TAK Newhouse, JS Denery, JR Galperin, MY Gonzalez, G Gilles-Gonzalez, MA Alam, M AF Wan, Xuehua Tuckerman, Jason R. Saito, Jennifer A. Freitas, Tracey Allen K. Newhouse, James S. Denery, Judith R. Galperin, Michael Y. Gonzalez, Gonzalo Gilles-Gonzalez, Marie-Alda Alam, Maqsudul TI Globins Synthesize the Second Messenger Bis-(3 '-5 ')-Cyclic Diguanosine Monophosphate in Bacteria SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE globin; oxygen sensor; c-di-GMP; diguanylate cyclase; biofilm ID CYCLIC-DI-GMP; BORDETELLA-PERTUSSIS; DIGUANYLATE CYCLASE; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; ALLOSTERIC CONTROL; CRYSTAL-STRUCTURE; COUPLED SENSORS; MYOGLOBIN; RECEPTOR AB Globin-coupled sensors are heme-bolding signal transducers in Bacteria and Archaea in which an N-terminal globin controls the activity of a variable C-terminal domain. Here, we report that BpeGReg, a globin-coupled diguanylate cyclase from the whooping cough pathogen Bordetella pertussis, synthesizes the second messenger bis-(3'-5')-cyclic diguanosine monophosphate (c-di-GMP) upon oxygen binding. Expression of BpeGReg m Salmonella typhimurium enhances biofilm formation, while knockout of the BpeGReg gene of B. pertussis results in decreased biofilm formation. These results represent the first identification a signal ligand for any diguanylate cyclase and provide definitive experimental evidence that a globin-coupled sensor regulates c-di-GMP synthesis and biofilm formation. We propose that the synthesis of c-di-GMP by globin sensors is a widespread phenomenon in bacteria. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wan, Xuehua; Saito, Jennifer A.; Freitas, Tracey Allen K.; Alam, Maqsudul] Univ Hawaii, Dept Microbiol, Honolulu, HI 96822 USA. [Tuckerman, Jason R.; Gonzalez, Gonzalo; Gilles-Gonzalez, Marie-Alda] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Newhouse, James S.; Alam, Maqsudul] Maui High Performance Comp Ctr, Maui, HI 96753 USA. [Denery, Judith R.] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. [Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Alam, Maqsudul] Univ Hawaii, Adv Studies Genom Prote & Bioinformat, Honolulu, HI 96822 USA. RP Alam, M (reprint author), Univ Hawaii, Dept Microbiol, 2538 McCarthy Mall,Snyder Hall 207, Honolulu, HI 96822 USA. EM alam@hawaii.edu RI Saito, Jennifer/B-7288-2011; Galperin, Michael/B-5859-2013; Wan, Xuehua/D-5433-2016 OI Galperin, Michael/0000-0002-2265-5572; Wan, Xuehua/0000-0002-6367-848X FU National Science Foundation [MCB0446431, 620531]; U.S. Army Telemedicine and Advanced Technology Research Center [W81XWH0520013]; National Institutes of Health Intramural Research Program at the National Center for Biotechnology Information; National Library of Medicine; National Institutes of Health; Welch Foundation [I-1575] FX This work was supported by the National Science Foundation (grant no. MCB0446431) and the U.S. Army Telemedicine and Advanced Technology Research Center (award no. W81XWH0520013) (M.A.); by the National Institutes of Health Intramural Research Program at the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health (M.Y.G.); and by the National Science Foundation (grant no. 620531) and Welch Foundation (grant no. I-1575) (M.A.G.G.). We thank Dr. C. Locht for providing the pFUS2 vector; Dr. G. Erdem, J. F. Teiber, and G. L. Kramer for providing laboratory facilities; Dr. D. Raze and C. Mizu.moto for technical assistance; Dr. H. Wahab and N. Bahiyalul for initial homology modeling; Dr. A. C. Whelen for providing the clinical strain of B. pertussis; Dr. E. H. S. Sousa for discussions; and Dr. G. Hazelbauer, Dr. C. Appleby, Dr. P. Patek, and Dr. D. Hunt for critical reading of the manuscript. NR 32 TC 46 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 1 PY 2009 VL 388 IS 2 BP 262 EP 270 DI 10.1016/j.jmb.2009.03.015 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 444FR UT WOS:000265966600006 PM 19285985 ER PT J AU Klausmeyer, P Zhou, Q Scudiero, DA Uranchimeg, B Melillo, G Cardellina, JH Shoemaker, RH Chang, CJ McCloud, TG AF Klausmeyer, Paul Zhou, Qin Scudiero, Dominic A. Uranchimeg, Badarch Melillo, Giovanni Cardellina, John H., II Shoemaker, Robert H. Chang, Ching-jer McCloud, Thomas G. TI Cytotoxic and HIF-1 alpha Inhibitory Compounds from Crossosoma bigelovii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID BREAST-TUMOR CELLS; INDUCIBLE FACTOR-I; CARDIAC-GLYCOSIDES; ANODENDRON-AFFINE; ACTIVATION; CONSTITUENTS; GROWTH AB Cytotoxicity-guided fractionation of an organic solvent extract of the plant Crossosoma bigelovii led to the discovery of a new strophanthidin glycoside (1) and two new 2-methylchromone glycosides (2 and 3). Also isolated were the known chromones eugenin and noreugenin, the indole alkaloid ajmalicine, the dibenzylbutane lignan secoisolariciresinol, the dibenzylbutyrolactone lignan matairesinol, and the furanone 5-tetradec-5-enyldihydrofuran-2-one. Further investigation into the biological properties of strophanthidin glycosides revealed a connection between inhibition of HIF-1 activation and the glycosylation of the genin. This work is the first published study of the bioactive phytochemicals of the family Crossosomataceae. C1 [Klausmeyer, Paul; McCloud, Thomas G.] SAIC Frederick Inc, Nat Prod Support Grp, NCI Frederick, Frederick, MD 21702 USA. [Zhou, Qin; Chang, Ching-jer] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Scudiero, Dominic A.] SAIC Frederick Inc, Mol Target Screening Program, NCI Frederick, Frederick, MD 21702 USA. [Uranchimeg, Badarch; Melillo, Giovanni] SAIC Frederick Inc, DTP Tumor Hypoxia Lab, NCI Frederick, Frederick, MD 21702 USA. [Cardellina, John H., II; Shoemaker, Robert H.] NCI Frederick, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP McCloud, TG (reprint author), SAIC Frederick Inc, Nat Prod Support Grp, NCI Frederick, Frederick, MD 21702 USA. EM mccloud@dtpax2.ncifcrf.gov FU National Cancer Institute, National Institutes of Health [R01-CA-49632, NO1-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts R01-CA-49632 (Purdue University) and NO1-CO-12400 (NCI). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. We gratefully acknowledge R. Spjut for the plant collection, J. Klose for NMR experiments, M. Selby for performing the HIF-1 and pGL3 biological screens, and J. Britt for robotics Support. NR 25 TC 11 Z9 11 U1 2 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2009 VL 72 IS 5 BP 805 EP 812 DI 10.1021/np8006342 PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 450GV UT WOS:000266389900001 PM 19405508 ER PT J AU Pettit, GR Quistorf, PD Fry, JA Herald, DL Hamel, E Chapuis, JC AF Pettit, George R. Quistorf, Peter D. Fry, Jeremy A. Herald, Delbert L. Hamel, Ernest Chapuis, Jean-Charles TI Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-2 SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID O-G RING; ALPHA,BETA-UNSATURATED ESTERS; NATURAL (-)-COMBRETASTATIN; BIOLOGICAL EVALUATION; MACROCYCLIC LACTONE; MITSUNOBU REACTION; COMBRETUM-CAFFRUM; CELL-GROWTH; VANCOMYCIN; TEICOPLANIN AB A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25-28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39-41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties. C1 [Pettit, George R.; Quistorf, Peter D.; Fry, Jeremy A.; Herald, Delbert L.; Chapuis, Jean-Charles] Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. [Hamel, Ernest] NCI, DTP, DCTC, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 871604, Tempe, AZ 85287 USA. EM bpettit@asu.edu FU NCI [Grant RO1 CA 90441-01-05]; Arizona Disease Control Research Commission; Fannie E. Rippel Foundation; Robert B. Dalton Endowment Fund FX We are pleased to acknowledge the financial Support provided by Grant RO1 CA 90441-01-05 with the Division of Cancer Treatment and Diagnosis, NCI, DHHS; the Arizona Disease Control Research Commission; the Fannie E. Rippel Foundation; the Robert B. Dalton Endowment Fund; and Gary L. and Diane R. Tooker, Dr. John C. Budzinski, and Sally Schloegel. For other helpful assistance we thank Drs. J. C. Knight, V. J. R. V. Mukku. R. K. Pettit, and M. S. Hoard, as well as M. Dodson, F. Cracitinescu, and C. A. Weber. NR 51 TC 13 Z9 14 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 2009 VL 72 IS 5 BP 876 EP 883 DI 10.1021/np800635h PG 8 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 450GV UT WOS:000266389900014 PM 20161135 ER PT J AU Jindrichova, M Vavra, V Obsil, T Stojilkovic, SS Zemkova, H AF Jindrichova, Marie Vavra, Vojtech Obsil, Tomas Stojilkovic, Stanko S. Zemkova, Hana TI Functional relevance of aromatic residues in the first transmembrane domain of P2X receptors SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ATP; deactivation; gating; ivermectin; P2XR; purinergic receptors; alpha beta-meATP ID AMINO-ACID-RESIDUES; GATED ION CHANNELS; ATP-BINDING-SITE; CATION PERMEABILITY; STRUCTURAL MOTIF; IDENTIFICATION; IVERMECTIN; SUBUNIT; REARRANGEMENTS; SUBSTITUTION AB The functional relevance of aromatic residues in the upper part of the transmembrane domain-1 of purinergic P2X receptors (P2XRs) was examined. Replacement of the conserved Tyr residue with Ala had a receptor-specific effect: the P2X1R was non-functional, the P2X2R, P2X4R, and P2X3R exhibited enhanced sensitivity to ATP and alpha beta-meATP accompanied by prolonged decay of current after washout of agonists, and the P2X7R sensitivity for agonists was not affected, though decay of current was delayed. The replacement of the P2X4R-Tyr42 with other amino acids revealed the relevance of an aromatic residue at this position. Mutation of the neighboring Phe and ipsilateral Tyr/Trp residues, but not the contralateral Phe residue, also affected the P2X2R, P2X3R, and P2X4R function. Double mutation of ipsilateral Tyr42 and Trp46 P2X4R residues restored receptor function, whereas the corresponding P2X2R double mutant was not functional. In contrast, mutation of the contralateral Phe48 residue in the P2X4R-Y42A mutant had no effect. These results indicate that aromatic residues in the upper part of TM1 play important roles in the three-dimensional structure of the P2XRs and that they are required not only for ion conductivity but also for specificity of agonist binding and/or channel gating. C1 [Jindrichova, Marie; Vavra, Vojtech; Obsil, Tomas; Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, CR-14220 Prague 4, Czech Republic. [Obsil, Tomas] Charles Univ Prague, Fac Sci, Dept Phys & Macromol Chem, Prague, Czech Republic. [Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Videnska 1083, CR-14220 Prague 4, Czech Republic. EM stojilks@mail.nih.gov; zemkova@biomed.cas.cz RI Vavra, Vojtech/C-1857-2012; Zemkova, Hana/C-1844-2012; Jindrichova, Marie/C-3401-2012; Obsil, Tomas/B-7142-2012; Jindrichova, Marie/H-4320-2014 OI Obsil, Tomas/0000-0003-4602-1272; FU Internal Grant Agency of Academy of Sciences [A5011408, IAA500110702, IAA500110910]; Academy of Sciences of the Czech Republic [AVOZ 50110509]; Center for Neuroscience [LC554]; Intramural Research Program of the NICHD, NIH FX This study was supported by the Internal Grant Agency of Academy of Sciences (Grants No. A5011408, IAA500110702 and IAA500110910), the Academy of Sciences of the Czech Republic (Research Project No. AVOZ 50110509), the Center for Neuroscience (Research Project No. LC554), and the Intramural Research Program of the NICHD, NIH. NR 39 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2009 VL 109 IS 3 BP 923 EP 934 DI 10.1111/j.1471-4159.2009.06021.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 430UD UT WOS:000265013700022 PM 19425179 ER PT J AU Kim, SM Choi, KY Cho, IH Rhy, JH Kim, SH Park, CS Kim, E Song, WK AF Kim, Seon-Myung Choi, Kyu Yeong Cho, In Ha Rhy, Jin Hee Kim, Sung Hyun Park, Chul-Seung Kim, Eunjoon Song, Woo Keun TI Regulation of dendritic spine morphology by SPIN90, a novel Shank binding partner SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cytoskeleton; dendritic spines; hippocampus; postsynaptic density; scaffolding protein ID POSTSYNAPTIC DENSITY PROTEINS; NEUROLOGICAL DISEASE; GLUTAMATE RECEPTORS; ACTIN CYTOSKELETON; SYNAPTIC FUNCTION; SUBSTRATE IRSP53; SMALL GTPASES; FAMILY; DYNAMICS; MORPHOGENESIS AB Dendritic spines are highly specialized actin-rich structures on which the majority of excitatory synapses are formed in the mammalian CNS. SPIN90 is an actin-binding protein known to be highly enriched in postsynaptic densities (PSDs), though little is known about its function there. Here, we show that SPIN90 is a novel binding partner for Shank proteins in the PSD. SPIN90 and Shank co-immunoprecipitate from brain lysates and co-localize in postsynaptic dendrites and act synergistically to mediate spine maturation and spine head enlargement. At the same time, SPIN90 causes accumulation of Shank and PSD-95 within dendritic spines. In addition, we found that the protein composition of PSDs in SPIN90 knockout mice is altered as is the actin cytoskeleton of cultured hippocampal SPIN90 knockout neurons. Taken together, these findings demonstrate that SPIN90 is a Shank1b binding partner and a key contributor to the regulation of dendritic spine morphogenesis and brain function. C1 [Song, Woo Keun] Gwangju Inst Sci & Technol, Dept Life Sci, Cell Dynam Res Ctr, Kwangju 500712, South Korea. [Kim, Seon-Myung; Cho, In Ha; Rhy, Jin Hee; Park, Chul-Seung; Song, Woo Keun] Gwangju Inst Sci & Technol, Bioimaging Ctr, Kwangju 500712, South Korea. [Choi, Kyu Yeong] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. [Kim, Sung Hyun] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. [Kim, Eunjoon] Korea Adv Inst Sci & Technol, Natl Creat Res Initiat Ctr Synaptogenesis, Dept Biol Sci, Taejon 305701, South Korea. RP Song, WK (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Cell Dynam Res Ctr, 261 Cheomdan Gwagiro, Kwangju 500712, South Korea. EM wksong@gist.ac.kr RI Kim, Eunjoon/C-1566-2011; OI Kim, Sung Hyun/0000-0002-3166-9941 FU Cell Dynamics Research Center [R11-2007-007-02001-0]; Bioimaging Research Center and Molecular and Cellular BioDiscovery Research Program [2006-02594] FX We thank Dr. Carlo Sala (University of Milan, Milan, Italy) for GFP-Shank1b constructs and Dr. Eunjoon Kim for HA-Shank1b constructs and Shank antibody. We also thank Dr. Chul-Seung Park for discussion and helpful suggestions. This work was supported in part by grants from the Cell Dynamics Research Center (R11-2007-007-02001-0), the Bioimaging Research Center and Molecular and Cellular BioDiscovery Research Program (2006-02594, Ministry of Education, Science and Technology). NR 49 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2009 VL 109 IS 4 BP 1106 EP 1117 DI 10.1111/j.1471-4159.2009.06039.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 433EK UT WOS:000265186900015 PM 19302483 ER PT J AU Riudavets, M Resnick, S Obrien, R Zonderman, A An, Y Sevlever, G Rudow, G Pletnikova, O Troncoso, J AF Riudavets, Miguel Resnick, Susan Obrien, Richard Zonderman, Alan An, Yang Sevlever, Gustavo Rudow, Gay Pletnikova, Olga Troncoso, Juan TI Distribution of Neuritic and Diffuse A beta Plaques in Brains of Subjects with AD and MCI: Implications for Brain Imaging of A beta SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 85th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 11-14, 2009 CL San Antonio, TX SP Amer Assoc Neuropathol C1 [Resnick, Susan; Zonderman, Alan; An, Yang] NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA. [Obrien, Richard] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Rudow, Gay; Pletnikova, Olga; Troncoso, Juan] Johns Hopkins Univ, Div Neuropathol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2009 VL 68 IS 5 MA 64 BP 568 EP 568 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 441GZ UT WOS:000265758600075 ER PT J AU Riudavets, M Resnick, S Obrien, R Zonderman, A An, Y Schultz, M Rudow, G Pletnikova, O Sevlever, G Troncoso, J AF Riudavets, Miguel Resnick, Susan Obrien, Richard Zonderman, Alan An, Yang Schultz, Marcelo Rudow, Gay Pletnikova, Olga Sevlever, Gustavo Troncoso, Juan TI Elevated Expression of Cell Cycle Proteins in Very Early Stages of Alzheimer's Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 85th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 11-14, 2009 CL San Antonio, TX SP Amer Assoc Neuropathol C1 [Resnick, Susan; Zonderman, Alan; An, Yang] NIA, Lab Personal & Cognit, Bethesda, MD 20892 USA. [Obrien, Richard] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Rudow, Gay; Pletnikova, Olga; Troncoso, Juan] Johns Hopkins Univ, Div Neuropathol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2009 VL 68 IS 5 MA 77 BP 571 EP 572 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 441GZ UT WOS:000265758600088 ER PT J AU Murthy, A Ray, S Shorter, SM Schall, JD Thompson, KG AF Murthy, Aditya Ray, Supriya Shorter, Stephanie M. Schall, Jeffrey D. Thompson, Kirk G. TI Neural Control of Visual Search by Frontal Eye Field: Effects of Unexpected Target Displacement on Visual Selection and Saccade Preparation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID LATERAL INTRAPARIETAL AREA; MONKEY SUPERIOR COLLICULUS; DOUBLE-STEP; COUNTERMANDING SACCADES; REACTION-TIME; PARIETAL CORTEX; RACE MODEL; FUNCTIONAL-PROPERTIES; RESPONSE PREPARATION; INHIBITORY CONTROL AB Murthy A, Ray S, Shorter SM, Schall JD, Thompson KG. Neural control of visual search by frontal eye field: effects of unexpected target displacement on visual selection and saccade preparation. J Neurophysiol 101:2485-2506, 2009. First published March 4, 2009; doi:10.1152/jn.90824.2008. The dynamics of visual selection and saccade preparation by the frontal eye field was investigated in macaque monkeys performing a search-step task combining the classic double-step saccade task with visual search. Reward was earned for producing a saccade to a color singleton. On random trials the target and one distractor swapped locations before the saccade and monkeys were rewarded for shifting gaze to the new singleton location. A race model accounts for the probabilities and latencies of saccades to the initial and final singleton locations and provides a measure of the duration of a covert compensation process-targetstep reaction time. When the target stepped out of a movement field, noncompensated saccades to the original location were produced when movement-related activity grew rapidly to a threshold. Compensated saccades to the final location were produced when the growth of the original movement-related activity was interrupted within target-step reaction time and was replaced by activation of other neurons producing the compensated saccade. When the target stepped into a receptive field, visual neurons selected the new target location regardless of the monkeys' response. When the target stepped out of a receptive field most visual neurons maintained the representation of the original target location, but a minority of visual neurons showed reduced activity. Chronometric analyses of the neural responses to the target step revealed that the modulation of visually responsive neurons and movement-related neurons occurred early enough to shift attention and saccade preparation from the old to the new target location. These findings indicate that visual activity in the frontal eye field signals the location of targets for orienting, whereas movement-related activity instantiates saccade preparation. C1 [Ray, Supriya; Shorter, Stephanie M.; Schall, Jeffrey D.] Vanderbilt Univ, Dept Psychol, Ctr Integrat & Cognit Neurosci, Vanderbilt Vis Res Ctr, Nashville, TN 37203 USA. [Murthy, Aditya] Natl Brain Res Ctr, Manesar, Haryana, India. [Thompson, Kirk G.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Schall, JD (reprint author), Vanderbilt Univ, Dept Psychol, Ctr Integrat & Cognit Neurosci, Vanderbilt Vis Res Ctr, 301 Wilson Hall,111 21st Ave S, Nashville, TN 37203 USA. EM jeffrey.d.schall@vanderbilt.edu FU Neuroscience and National Institutes of Health [T32 EY-08126, F32 EY-14502, R01 EY-8890, P30 EY-08126, P30 HD-015052] FX This work was supported by Robin and Richard Patton through the E. Bronson Ingram Chair in Neuroscience and National Institutes of Health Grants T32 EY-08126, F32 EY-14502, R01 EY-8890, P30 EY-08126, and P30 HD-015052. NR 110 TC 40 Z9 40 U1 2 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2009 VL 101 IS 5 BP 2485 EP 2506 DI 10.1152/jn.90824.2008 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 436FM UT WOS:000265398100030 PM 19261711 ER PT J AU Spampinato, MV Wood, JN De Simone, V Grafman, J AF Spampinato, Maria Vittoria Wood, Jacqueline N. De Simone, Veronica Grafman, Jordan TI Neural Correlates of Anxiety in Healthy Volunteers: A Voxel-Based Morphometry Study SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; SMALLER HIPPOCAMPAL VOLUME; CHILDHOOD SEXUAL-ABUSE; GRAY-MATTER DENSITY; CEREBRAL-BLOOD-FLOW; PANIC DISORDER; AMYGDALA; BRAIN; MRI AB Studies have shown that the amygdala, temporal, and prefrontal cortices play a key role in the expression of anxiety. The correlation between gray matter volume of these structures and behavioral anxiety measures was not previously investigated in healthy volunteers. The authors used voxel-based morphometry to assess the relationship between brain regional volume and anxiety. The authors found an inverse correlation between anxiety measures and cortical volume in regions of the limbic system and prefrontal cortex implicated in the pathogenesis of anxiety disorders. The authors suggest that volumetric variability of these regions may have a correlation with the development of an anxious personality trait. C1 [Wood, Jacqueline N.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Spampinato, Maria Vittoria] Med Univ S Carolina, Dept Radiol, Charleston, SC USA. [De Simone, Veronica] Hosp Britan Buenos Aires, Buenos Aires, DF, Argentina. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 7D43 MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 47 TC 42 Z9 42 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD MAY PY 2009 VL 21 IS 2 BP 199 EP 205 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 472SL UT WOS:000268152300013 PM 19622691 ER PT J AU Itoh, T Abe, K Zoghbi, SS Inoue, O Hong, JS Imaizumi, M Pike, VW Innis, RB Fujita, M AF Itoh, Tetsuji Abe, Kohji Zoghbi, Sami S. Inoue, Osamu Hong, Jinsoo Imaizumi, Masao Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI PET Measurement of the In Vivo Affinity of C-11-(R)-Rolipram and the Density of Its Target, Phosphodiesterase-4, in the Brains of Conscious and Anesthetized Rats SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE small-animal PET; isoflurane; compartmental analysis; transient equilibrium; cAMP ID CAMP-SPECIFIC PHOSPHODIESTERASE; POSITRON-EMISSION-TOMOGRAPHY; DOPAMINE-RECEPTORS; ROLIPRAM BINDING; PROTEIN-KINASE; PHOSPHORYLATION; PDE4; ANESTHESIA; MONKEY; AUTORADIOGRAPHY AB A variety of phosphodiesterases hydrolyze and terminate the effects of the intracellular second messenger 3',5'-cyclic adenosine monophosphate (cAMP). Phosphodiesterase subtype 4 (PDE4) is particularly abundant in the brain and has been imaged with C-11-(R)-rolipram, a selective inhibitor of PDE4. We sought to measure in vivo both the binding site density (B-max) and the radioligand affinity (1/K-D) of C-11-(R)-rolipram in the rat brain. We also studied 2 critical factors in small-animal PET scans: the influence of anesthesia and the difference in binding under in vivo and in vitro conditions. Methods: In vivo, B-max and K-D were measured in PET saturation experiments by the administration of C-11-(R)-rolipram and various doses of carrier (R)-rolipram in conscious and isoflurane-anesthetized rats. The metabolite-corrected arterial input function was measured in each scan. To image conscious rats, the head of the rat was fixed in a holder and the animals were trained to comply with this apparatus. Bound and free (R)-rolipram levels were calculated under transient equilibrium conditions (i.e., at the time of peak specific binding). Results: The B-max and K-D of conscious rats were significantly greater than those of anesthetized rats, by 29% and 59%, respectively. In addition, the in vitro K-D was 3-7 times greater than was the in vivo K-D, although the B-max was similar in both conditions. Conclusion: The in vivo B-max and K-D of (R)-rolipram were successfully measured in both conscious and anesthetized rats. K-D was affected to a greater extent than was B-max by the 2 conditions. That is, K-D was increased in the conscious rat, compared with in the anesthetized rat, and K-D was increased in vitro, compared with in vivo. The current study shows that the rat, a readily available species for research, can be used to measure in vivo both affinity and density of radioligand targets, which can later be directly assessed with standard in vitro techniques. C1 [Itoh, Tetsuji; Zoghbi, Sami S.; Hong, Jinsoo; Imaizumi, Masao; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Abe, Kohji] Shionogi & Co Ltd, Dev Res Labs, Osaka, Japan. [Abe, Kohji; Inoue, Osamu] Osaka Univ, Grad Sch Med, Div Hlth Sci, Osaka, Japan. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 31,Room B2B37,31 Ctr Dr,MSC-2035, Bethesda, MD 20892 USA. EM FujitaM@intra.nimh.nih.gov FU Intramural Program of NIMH [Z01-MH-002795-07] FX We thank Robert Gladding, Matthew Crescenzo, JeihSan Liow, Edward Tuan, and Jonathan Gourley for assisting with PET experiments and data processing; Jurgen Seidel and Michael Green for developing the small-animal PET scanner; PMOD Technologies (Zurich, Switzerland) for providing its image-analysis and modeling software; Antony Gee for providing the precursor of 11C-(R)rolipram; David Luckenbaugh for assisting with statistical analyses; Alan Hoofring and Ethan Tyler for drawing schematic diagrams; Ioline Henter for editorial assistance; and Ronald Duman for helpful discussions. This research was supported by the Intramural Program of NIMH (project Z01-MH-002795-07). NR 30 TC 17 Z9 17 U1 2 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2009 VL 50 IS 5 BP 749 EP 756 DI 10.2967/jnumed.108.058305 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 529AK UT WOS:000272487900013 PM 19372471 ER PT J AU Seneca, N Zoghbi, SS Liow, JS Kreisl, W Herscovitch, P Jenko, K Gladding, RL Taku, A Pike, VW Innis, RB AF Seneca, Nicholas Zoghbi, Sami S. Liow, Jeih-San Kreisl, William Herscovitch, Peter Jenko, Kimberly Gladding, Robert L. Taku, Andrew Pike, Victor W. Innis, Robert B. TI Human Brain Imaging and Radiation Dosimetry of C-11-N-Desmethyl-Loperamide, a PET Radiotracer to Measure the Function of P-Glycoprotein SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; N-desmethyl-loperamide; P-glycoprotein ID 2-DIMENSIONAL PLANAR; NONHUMAN-PRIMATES; BIODISTRIBUTION; RADIOLIGAND; BARRIER; RADIOMETABOLITE; TRACER AB P-glycoprotein (P-gp) is a membrane-bound efflux pump that limits the distribution of drugs to several organs of the body. At the blood-brain barrier, P-gp blocks the entry of both loperamide and its metabolite, N-desmethyl-loperamide (N-dLop), and thereby prevents central opiate effects. Animal studies have shown that C-11-dLop, compared with C-11-loperamide, is an especially promising radiotracer because it generates negligible radiometabolites that enter the brain. The purposes of this study were to determine whether C-11-dLop is a substrate for P-gp at the blood-brain barrier in humans and to measure the distribution of radioactivity in the entire body to estimate radiation exposure. Methods: Brain PET scans were acquired in 4 healthy subjects for 90 min and included concurrent measurements of the plasma concentration of unchanged radiotracer. Time-activity data from the whole brain were quantified using a 1-tissue-compartment model to estimate the rate of entry (K-1) of radiotracer into the brain. Whole-body PET scans were acquired in 8 healthy subjects for 120 min. Results: For brain imaging, after the injection of C-11-dLop the concentration of radioactivity in the brain was low (standardized uptake value, similar to 15%) and stable after approximately 20 min. In contrast, uptake of radioactivity in the pituitary was about 50-fold higher than that in the brain. The plasma concentration of C-11-dLop declined rapidly, but the percentage composition of plasma was unusually stable, with the parent radiotracer constituting 85% of total radioactivity after approximately 5 min. The rate of brain entry was low (K-1 = 0.009 +/- 0.002 mL.cm(-3.)min(-1); n = 4). For whole-body imaging, as a measure of radiation exposure to the entire body the effective dose of C-11-dLop was 7.8 +/- 0.6 mu Sv/MBq (n = 8). Conclusion: The low brain uptake of radioactivity is consistent with C-11-dLop being a substrate for P-gp in humans and confirms that this radiotracer generates negligible quantities of brain-penetrant radiometabolites. In addition, the low rate of K-1 is consistent with P-gp rapidly effluxing substrates while they transit through the lipid bilayer. The radiation exposure of C-11-dLop is similar to that of many other C-11-radiotracers. Thus, C-11-dLop is a promising radiotracer to study the function of P-gp at the blood-brain barrier, at which impaired function would allow increased uptake into the brain. C1 [Seneca, Nicholas; Zoghbi, Sami S.; Liow, Jeih-San; Kreisl, William; Jenko, Kimberly; Gladding, Robert L.; Taku, Andrew; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU Intramural NIH HHS [Z01 MH002852-04]; NIMH NIH HHS [Z01 MH002852, Z01-MH-002852-04] NR 21 TC 44 Z9 45 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY 1 PY 2009 VL 50 IS 5 BP 807 EP 813 DI 10.2967/jnumed.108.058453 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 529AK UT WOS:000272487900020 PM 19372478 ER PT J AU Monge-Rojas, R Garita-Arce, C Sanchez-Lopez, M Colon-Ramos, U AF Monge-Rojas, Rafael Garita-Arce, Carlos Sanchez-Lopez, Marta Colon-Ramos, Uriyoan TI Barriers to and Suggestions for a Healthful, Active Lifestyle as Perceived by Rural and Urban Costa Rican Adolescents SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE adolescent; physical activity; healthful; active lifestyle; health education ID YOUTH PHYSICAL-ACTIVITY; GENDER-DIFFERENCES; SOCIAL SUPPORT; ENVIRONMENTS; BEHAVIORS; ASSOCIATION; CHILDREN; OBESITY; GIRLS; PARTICIPATION AB Objective: To assess the perceptioris of rural and urban Costa Rican adolescents regarding which barriers and motivators affect their adoption of art active lifestyle. Design: Data were collected in focus group discussion. Participants: 108 male and female adolescents aged 12 to 18 from the 7th to 11th grades. Setting: Two urban and 1 rural high school in San Jose, Costa Rica. Phenomena of Interest: Active lifestyle; barriers and motivators for active life. Analysis: of an activc lifestyle. Analysis: Data were reviewed for emerging, and themes were coded using content analysis procedures. Results: Major barriers: (a) physical education curriculum was focused on competitive sports; (b) lack of facilities in the school and community environments; (c) family did not provide good role models and re-inforced the socially expected gender roles. Key motivators: (a) changed the physical education curriculum to focus on leisure and recreational activities; (b) increased the availability of facilities both in the school and in the community; and (c) provided a strong social support network. Conclusions and Implications: The school, community, and family environments are potential targets for physical activity interventions for adolescents. Future studies should explore in depth the influence of adolescent socialization patterns (particularly for females) in the establishmed of an active lifestyle. C1 [Monge-Rojas, Rafael] INCIENSA, Minist Hlth, Tres Rios, Costa Rica. [Garita-Arce, Carlos] Costa Rican Social Secur Fund CCSS, Comprehens Healthcare Program Adolescents, San Jose, Costa Rica. [Sanchez-Lopez, Marta] Univ Nacl UNA, Dept Psychol, Heredia, Costa Rica. [Colon-Ramos, Uriyoan] NCI, Behav Res Program, Bethesda, MD 20892 USA. RP Monge-Rojas, R (reprint author), INCIENSA, Minist Hlth, Apartado 4-2250, Tres Rios, Costa Rica. EM rmonge@inciensa.sa.cr NR 47 TC 10 Z9 10 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAY-JUN PY 2009 VL 41 IS 3 BP 152 EP 160 DI 10.1016/j.jneb.2008.03.002 PG 9 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 443HF UT WOS:000265900100003 PM 19411048 ER PT J AU Shahar, DR Yu, B Houston, DK Kritchevsky, SB Lee, JS Rubin, SM Sellmeyer, DE Tylavsky, FA Harris, TB AF Shahar, D. R. Yu, B. Houston, D. K. Kritchevsky, S. B. Lee, J. -S. Rubin, S. M. Sellmeyer, D. E. Tylavsky, F. A. Harris, T. B. CA Hlth Aging & Body Composition Stud TI Dietary factors in relation to daily activity energy expenditure and mortality among older adults SO JOURNAL OF NUTRITION HEALTH & AGING LA English DT Article DE Elderly; appetite; diet; energy expenditure; mortality ID HEALTHY EATING INDEX; DOUBLY LABELED WATER; STYLE RISK-FACTORS; ELDERLY-PEOPLE; MEDITERRANEAN DIET; WEIGHT-LOSS; COMMUNITY; LIFE; POPULATION; PATTERNS AB To examine the association between dietary factors to daily activity energy expenditure (DAEE) and mortality among older adults. A sub-study of Health, Aging, and Body Composition study. 298 older participants (aged 70-82 years) in the Health, Aging, and Body Composition Energy Expenditure sub-study. Dietary factors, DAEE, and all-cause mortality were measured in 298 older participants. Dietary factors include dietary intake assessed by the Block Food Frequency Questionnaire (FFQ), Healthy Eating Index (HEI), and self-reported appetite and enjoyment of eating. DAEE was assessed using doubly labeled water. All-cause mortality was evaluated over a 9 year period. Participants in the highest tertile of DAEE were more likely to be men and to report having a 'good' appetite; BMI among men, proportion married, IL-6 and CRP levels and energy intake were also higher. Fewer black participants were in the 'good' HEI category. Participants in the 'good' HEI category had higher cognitive scores and a higher education level. Participants who reported improvement in their appetite as well as participants who reported a 'good' appetite were at lower risk for mortality (HR (95% CI): 0.42 (0.24-0.74) and 0.50 (0.26-0.88), respectively) even after adjusting for DAEE, demographic, nutritional and health indices. We showed an association between DAEE and appetite and mortality among well-functioning, community-dwelling older adults. These findings may have some practical use for the health providers. Inclusion of a question regarding appetite of an elderly patient may provide important information regarding risk for health deterioration and mortality. C1 [Shahar, D. R.] Ben Gurion Univ Negev, S Daniel Abraham Int Ctr Hlth & Nutr, IL-84105 Beer Sheva, Israel. [Shahar, D. R.] Ben Gurion Univ Negev, Dept Epidemiol & Hlth Evaluat, IL-84105 Beer Sheva, Israel. [Shahar, D. R.; Yu, B.; Harris, T. B.; Hlth Aging & Body Composition Stud] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Houston, D. K.; Kritchevsky, S. B.] Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Lee, J. -S.] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Rubin, S. M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Sellmeyer, D. E.] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Tylavsky, F. A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. RP Shahar, DR (reprint author), Ben Gurion Univ Negev, S Daniel Abraham Int Ctr Hlth & Nutr, IL-84105 Beer Sheva, Israel. EM dshahar@bgu.ac.il RI Shahar, Danit/B-4280-2012 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH FX This study was supported by National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 with additional support from the National Institute of Diabetes and Digestive and Kidney Diseases. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 44 TC 18 Z9 19 U1 1 U2 4 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-7707 J9 J NUTR HEALTH AGING JI J. Nutr. Health Aging PD MAY PY 2009 VL 13 IS 5 BP 414 EP 420 DI 10.1007/s12603-009-0077-y PG 7 WC Geriatrics & Gerontology; Nutrition & Dietetics SC Geriatrics & Gerontology; Nutrition & Dietetics GA 445GJ UT WOS:000266038100003 PM 19390747 ER PT J AU Jung, KJ Go, EK Kim, JY Yu, BP Chung, HY AF Jung, Kyung Jin Go, Eun Kyung Kim, Ji Young Yu, Byung Pal Chung, Hae Young TI Suppression of age-related renal changes in NF-kappa B and its target gene expression by dietary ferulate SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Ferulate; Oxidative stress; NF-kappa B; Aging; Proinflammatory genes; NIK/IKK; MAPKs ID CALORIE RESTRICTION; OXIDATIVE STRESS; INFLAMMATION HYPOTHESIS; TRANSCRIPTION FACTORS; LIPID-PEROXIDATION; IN-VITRO; KINASE; ACID; ACTIVATION; CELLS AB Ferulate is a well-described natural antioxidant found in plants. It protects against cellular redox disruption and several oxidative stress-related diseases, including inflammation in animal studies. In this study, we examined ferulate for its ability to suppress redox-sensitive, proinflammatory NF-kappa B activation via NF-kappa B-inducing kinase (NIK)/IkappaB kinase (IKK) and mitogen-activated protein kinases (MAPKs) by reducing oxidative stress in aged rats. The experimental design was set as follows: Sprague-Dawley rats, ages 7 months (young) and 20 months (old) were used in this study, and dietary ferulate (0.01% or 0.02%) was fed to the old rats for 10 days. Data show that in aged kidney tissue, ferulate exhibited its antioxidative action by maintaining redox regulation, suppressing NF-kappa B activation and modulating the expression of NF-kappa B-induced, proinflammatory COX-2, iNOS, VCAM-1 and ICAM-1. Next, we examined cultured YPEN-1 endothelial cells and show that ferulate protected YPEN-1 cells against tert-butylhydroperoxide-induced oxidative stress. The molecular modulation of NF-kappa B by ferulate was further revealed in endothelial YPEN-1 cells through ferulate's ability to suppress the activation of NIK/IKK and MAPKs. Based on these results, we conclude that ferulate's antioxidative capacity suppressed the age-related increase in NF-kappa B activity through inhibition of NIK/IKK and MAPKs in vivo. This study may also suggest the potentiality of ferulate as a developable supplement against chronic inflammatory disease as well as aging. (C) 2009 Elsevier Inc. All rights reserved. C1 [Go, Eun Kyung; Kim, Ji Young; Chung, Hae Young] Pusan Natl Univ, Coll Pharm, Dept Pharm, Pusan 609735, South Korea. [Yu, Byung Pal; Chung, Hae Young] Pusan Natl Univ, Longev Life Sci & Technol Inst, Pusan 609735, South Korea. [Yu, Byung Pal] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Jung, Kyung Jin] NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Chung, HY (reprint author), Pusan Natl Univ, Coll Pharm, Dept Pharm, Pusan 609735, South Korea. EM hyjung@pusan.ac.kr FU Korea Science and Engineering Foundation [2006-04978] FX This work was supported by the Korea Science and Engineering Foundation grant funded by the Korean government (MOST) (No. 2006-04978). We are grateful to the 'Aging Tissue Bank' for supplying aged tissue. The authors thank the NCI, CCR Fellows Editorial Board for valuable editing of this article. NR 41 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD MAY PY 2009 VL 20 IS 5 BP 378 EP 388 DI 10.1016/j.jnutbio.2008.04.008 PG 11 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 434YQ UT WOS:000265310600006 PM 18657961 ER PT J AU Yeganova, L Wilbur, WJ AF Yeganova, L. Wilbur, W. J. TI Isotonic Regression under Lipschitz Constraint SO JOURNAL OF OPTIMIZATION THEORY AND APPLICATIONS LA English DT Article DE Isotonic regression; Lipschitz continuous function; PAV algorithm AB The pool adjacent violators (PAV) algorithm is an efficient technique for the class of isotonic regression problems with complete ordering. The algorithm yields a stepwise isotonic estimate which approximates the function and assigns maximum likelihood to the data. However, if one has reasons to believe that the data were generated by a continuous function, a smoother estimate may provide a better approximation to that function. In this paper, we consider the formulation which assumes that the data were generated by a continuous monotonic function obeying the Lipschitz condition. We propose a new algorithm, the Lipschitz pool adjacent violators (LPAV) algorithm, which approximates that function; we prove the convergence of the algorithm and examine its complexity. C1 [Yeganova, L.; Wilbur, W. J.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Yeganova, L (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM yeganova@ncbi.nlm.nih.gov; wilbur@ncbi.nlm.nih.gov FU Intramural Research Program of NIH; National Library of Medicine FX The authors were supported by the Intramural Research Program of NIH, National Library of Medicine. NR 6 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-3239 J9 J OPTIMIZ THEORY APP JI J. Optim. Theory Appl. PD MAY PY 2009 VL 141 IS 2 BP 429 EP 443 DI 10.1007/s10957-008-9477-0 PG 15 WC Operations Research & Management Science; Mathematics, Applied SC Operations Research & Management Science; Mathematics GA 436AC UT WOS:000265384000012 ER PT J AU Sheehan, FT Derasari, A Brindle, TJ Alter, KE AF Sheehan, Frances T. Derasari, Aditya Brindle, Timothy J. Alter, Katharine E. TI Understanding Patellofemoral Pain with Maltracking in the Presence of Joint Laxity: Complete 3D In Vivo Patellofemoral and Tibiofemoral Kinematics SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE patellofemoral; tibiofemoral; magnetic resonance imaging; Ehlers Danlos syndrome; dynamic; kinematics ID KNEE-JOINT; PATELLAR TRACKING; WEIGHT-BEARING; INDIVIDUALS; ASSOCIATION; ALIGNMENT; HYPERMOBILITY; DISORDERS; EXTENSION; SYMPTOMS AB Patellofemoral pain is widely accepted as one of the most common pathologies involving the knee, yet the etiology of this pain is still an open debate. Generalized joint laxity has been associated with patellofemoral pain, but is not often discussed as a potential source of patellar maltracking. Thus, the objective of this study was to compare the comptete 6 degree of freedom patellofemoral and tibiofemoral kinematics from a group of patients diagnosed with patellofernoral pain syndrome and maltracking to those from an asymtomatic population. The following null hypotheses were tested: kinematic alterations in patellotemoral maltracking are limited to the axial plane; knee joint kinematics are the same in maltrackers with and without generalized joint laxity (defined by a clinical diagnosis of Ehlers Danlos Syndrome); and no correlations exist between tibiotemoral and patellofemoral kinematics or within patellofemoral kinematics. This study demonstrated that alterations in patellofemoral kinematics, associated with patellofemoral pain, are not limited to the axial plane, minimal correlations exist between patellofemoral and tibiofemoral kinematics, and distinct subgroups likely exist within the general population of maltrackers. Being able to identify subgroups correctly within the omnibus diagnosis of patellar maltracking is a crucial step in correctly defining the pathophysiology and the eventual of these patients. (C) 2008 Orthopaedic Research Society. *Published by Wiley Periodicals, Inc. J Orthop Res 27:561-570, 2009 C1 [Sheehan, Frances T.; Brindle, Timothy J.; Alter, Katharine E.] NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. [Derasari, Aditya] Univ Miami, Dept Orthopaed, Miami, FL USA. [Alter, Katharine E.] Mt Washington Pediat Hosp, Baltimore, MD USA. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, Bldg 10,RM 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU NIH FX We thank Elizabeth K. Rasch. PT, PhD, for Support on statistical analysis and Steven Stanhope, PhD, for guidance. We also thank Bonnie Damaska, Jamie Fraunhaffer. Jere McLucas, and the Diagnostic Radiology Department at NIH for their support and time. Salary support for Brindle, Sheehan, and Alter was provided through NIH. Salary support for Desari was provided by the Howard Hughes Medical Institute. Any opinions, findings, and conclusions or recomnendations expressed in this material are those of the author and do not necessarily reflect the views of the NIH or the US Public Health Service. NR 42 TC 33 Z9 35 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2009 VL 27 IS 5 BP 561 EP 570 DI 10.1002/jor.20783 PG 10 WC Orthopedics SC Orthopedics GA 430SW UT WOS:000265009900001 PM 19009601 ER PT J AU Mazaki-Tovi, S Romero, R Kusanovic, JP Vaisbuch, E Erez, O Than, NG Chaiworapongsa, T Nhan-Chang, CL Pacora, P Gotsch, F Yeo, L Kim, SK Edwin, SS Hassan, SS Mittal, P AF Mazaki-Tovi, Shali Romero, Roberto Kusanovic, Juan Pedro Vaisbuch, Edi Erez, Offer Than, Nandor Gabor Chaiworapongsa, Tinnakorn Nhan-Chang, Chia-Ling Pacora, Percy Gotsch, Francesca Yeo, Lami Kim, Sun Kwon Edwin, Samuel S. Hassan, Sonia S. Mittal, Pooja TI Maternal visfatin concentration in normal pregnancy SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Adipokines; obesity; overweight; pregnancy; visfatin ID COLONY-ENHANCING FACTOR; GESTATIONAL DIABETES-MELLITUS; TUMOR-NECROSIS-FACTOR; PLASMA ADIPONECTIN CONCENTRATIONS; HUMAN FETAL MEMBRANES; HUMAN ADIPOSE-TISSUE; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; IMPAIRED GLUCOSE-TOLERANCE; MESSENGER-RIBONUCLEIC-ACID AB Objective: Adipose tissue has now emerged as a powerful endocrine organ via the production of adipokines. Visfatin, a novel adipokine with diabetogenic and immunomodulatory properties has been implicated in the pathophysiology of insulin resistance in patients with obesity and Type-2 diabetes mellitus. The aim of this study was to determine whether there are changes in the maternal plasma concentration of visfatin with advancing gestation and as a function of maternal weight. Study design: In this cross-sectional study, maternal plasma concentrations of visfatin were determined in normal weight and overweight/obese pregnant women in the following gestational age groups: 1) 11-14 weeks (n=52); 2) 19-26 weeks (n=68); 3) 27-34 weeks (n=93); and 4) >37 weeks (n=60). Visfatin concentrations were determined by ELISA. Non parametric statistics were used for analysis. Results: 1) The median maternal plasma visfatin concentration was higher in pregnant women between 19-26 weeks of gestation than that of those between 11-14 weeks of gestation (P<0.01) and those between 27-34 weeks of gestation (P<0.01); 2) among normal weight pregnant women, the median plasma visfatin concentrations of women between 19-26 weeks of gestation was higher than that of those between 11-14 weeks (P<0.01) and those between 27-34 weeks (P<0.01); and 3) among overweight/obese patients, the median maternal visfatin concentration was similar between the different gestational age groups. Conclusion: The median maternal plasma concentration of visfatin peaks between 19-26 and has a nadir between 27-34 weeks of gestation. Normal and overweight/obese pregnant women differed in the pattern of changes in circulating visfatin concentrations as a function of gestational age. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Pacora, Percy; Gotsch, Francesca; Yeo, Lami; Kim, Sun Kwon; Edwin, Samuel S.; Hassan, Sonia S.; Mittal, Pooja] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Pacora, Percy; Gotsch, Francesca; Yeo, Lami; Kim, Sun Kwon; Edwin, Samuel S.; Hassan, Sonia S.; Mittal, Pooja] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Bethesda, MD USA. [Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Yeo, Lami; Hassan, Sonia S.; Mittal, Pooja] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 203 TC 32 Z9 37 U1 0 U2 3 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 EI 1619-3997 J9 J PERINAT MED JI J. Perinat. Med. PD MAY PY 2009 VL 37 IS 3 BP 206 EP 217 DI 10.1515/JPM.2009.054 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 444YF UT WOS:000266016100002 PM 19284295 ER PT J AU Mazaki-Tovi, S Romero, R Kusanovic, JP Vaisbuch, E Erez, O Than, NG Chaiworapongsa, T Nhan-Chang, CL Pacora, P Gotsch, F Yeo, L Kim, SK Edwin, SS Hassan, SS Mittal, P AF Mazaki-Tovi, Shali Romero, Roberto Kusanovic, Juan Pedro Vaisbuch, Edi Erez, Offer Than, Nandor Gabor Chaiworapongsa, Tinnakorn Nhan-Chang, Chia-Ling Pacora, Percy Gotsch, Francesca Yeo, Lami Kim, Sun Kwon Edwin, Samuel S. Hassan, Sonia S. Mittal, Pooja TI Visfatin in human pregnancy: maternal gestational diabetes vis-a-vis neonatal birthweight SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE adipokine; adipose tissue; appropriate-for-gestational-age (AGA); gestational diabetes mellitus (GDM); large-for-gestational-age (LGA); pre-B cell colony-enhancing factor (PBEF); visfatin ID COLONY-ENHANCING FACTOR; IMPAIRED GLUCOSE-TOLERANCE; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA EXPRESSION; HUMAN FETAL MEMBRANES; PLASMA ADIPONECTIN CONCENTRATIONS; LINKED-IMMUNOSORBENT-ASSAY; POLYCYSTIC-OVARY-SYNDROME; INSULIN-RESISTANCE; ADIPOSE-TISSUE AB Objective: Adipose tissue dysfunction, characterized by dysregulation of adipokines production and/or secretion, has been implicated in the pathophysiology of type-2 diabetes mellitus, a metabolic complication closely related to gestational diabetes mellitus (GDM). Recently, an association between circulating maternal visfatin, a novel adipokine with metabolic and immunoregulatory properties, and impaired glucose metabolism as well as with altered fetal growth, has been proposed. The aims of this study were to determine whether there is an association between maternal plasma visfatin concentration, GDM, and a large-for-gestational-age (LGA) newborn. Study design: This cross-sectional study, included pregnant women at term in the following groups: 1) normal pregnancy and an appropriate-for-gestational-age (AGA) neonate (n=54); 2) normal pregnancy and an LGA newborn (n=47); 3) GDM and an AGA newborn (n=56); 4) GDM and an LGA newborn (n=45). The study population was further stratified by first trimester BMI (<25 vs. >= 25 kg/m(2)). Maternal plasma visfatin concentration was determined by ELISA. Parametric and non-parametric statistics were used for analysis. Results: 1) Among women who delivered an AGA neonate, the median maternal plasma concentration of visfatin was higher in patients with GDM than in those with a normal pregnancy; 2) Among women with a normal pregnancy, those who delivered an LGA neonate had a higher median maternal plasma visfatin concentration than those who delivered an AGA neonate; 3) among patients with normal BMI, there were no significant differences in the median maternal plasma visfatin concentration between the four study groups; and 4) maternal GDM, as well as delivery of an LGA neonate were independently associated with a higher maternal plasma visfatin concentrations. Conclusion: The linkage between increased maternal circulating visfatin and the presence of GDM or delivery of an LGA neonate supports the hypothesis that perturbation of adipokines homeostasis may play a role in the pathophysiology of GDM or excess fetal growth. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Pacora, Percy; Gotsch, Francesca; Yeo, Lami; Kim, Sun Kwon; Edwin, Samuel S.; Hassan, Sonia S.; Mittal, Pooja] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Romero, Roberto; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Than, Nandor Gabor; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Pacora, Percy; Gotsch, Francesca; Yeo, Lami; Kim, Sun Kwon; Edwin, Samuel S.; Hassan, Sonia S.; Mittal, Pooja] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Bethesda, MD USA. [Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn; Nhan-Chang, Chia-Ling; Yeo, Lami; Hassan, Sonia S.; Mittal, Pooja] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div,DHHS, NICHD,NIH, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 204 TC 30 Z9 31 U1 0 U2 6 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 EI 1619-3997 J9 J PERINAT MED JI J. Perinat. Med. PD MAY PY 2009 VL 37 IS 3 BP 218 EP 231 DI 10.1515/JPM.2009.053 PG 14 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 444YF UT WOS:000266016100003 PM 19099366 ER PT J AU Hiranita, T Soto, PL Newman, AH Katz, JL AF Hiranita, Takato Soto, Paul L. Newman, Amy H. Katz, Jonathan L. TI Assessment of Reinforcing Effects of Benztropine Analogs and Their Effects on Cocaine Self-Administration in Rats: Comparisons with Monoamine Uptake Inhibitors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Centennial Symposium of the American-Society-for-Pharmacology-and-Experimental-Therapeutics held at the Experimental Biology 2008 Annual Meeting CY APR 06, 2008 CL San Diego, CA SP Amer Soc Pharmacol & Expt Therapeut ID DOPAMINE TRANSPORTER LIGAND; RHESUS-MONKEYS; POPULATION PHARMACOKINETICS; BEHAVIORAL PHARMACOLOGY; DRUG DISCRIMINATION; LOCOMOTOR-ACTIVITY; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS; IN-VITRO; OCCUPANCY AB Benztropine (BZT) analogs inhibit dopamine uptake but are less effective than cocaine in producing behavioral effects predicting abuse liability. The present study compared reinforcing effects of intravenous BZT analogs with those of standard monoamine uptake inhibitors and the effects of their oral pretreatment on cocaine self-administration. Responding of rats was maintained by cocaine [0.032-1.0 mg/kg/ injection (inj)] or food reinforcement under fixed-ratio five-response schedules. Maximal rates of responding were maintained by 0.32 mg/kg/ inj cocaine or substituted methylphenidate, with lower rates maintained at lower and higher doses. The N-methyl BZT analog, AHN 1-055 (3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane), also maintained responding (0.1 mg/kg/ inj), although maximal rates were less than those with cocaine. Responding was not maintained above vehicle levels by the N-allyl, AHN 2-005 (N-allyl-3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane), and N-butyl, JHW 007 [N-(n-butyl)-3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane], BZT analogs, and it was not maintained with nisoxetine or citalopram. Presession treatment with methylphenidate (3.2-32 mg/kg) dose-dependently shifted the cocaine self-administration dose-effect curve leftward, whereas nisoxetine and citalopram effects were not significant. An intermediate dose of AHN 1-055 (32 mg/kg) increased responding maintained by low cocaine doses and decreased responding maintained by higher doses. A higher dose of AHN 1-055 completely suppressed cocaine-maintained responding. Both AHN 2-005 and JHW 007 dose-dependently (10-32 mg/kg) decreased cocaine self-administration, shifting its dose-effect curve down. Decreases in cocaine-maintained responding occurred at doses of methylphenidate and BZT analogs that left food-maintained responding unchanged. During a component in which injections were not available, methylphenidate and AHN 1-055, but not AHN 2-005 or JHW 007, increased response rates. These findings further support the low abuse liability of BZT analogs and their potential development as medications for cocaine abuse. C1 [Hiranita, Takato; Soto, Paul L.; Katz, Jonathan L.] Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program,Dept Hlth & Human Serv, Psychobiol Sect,Medicat Discovery Res Branch, Baltimore, MD 21224 USA. [Newman, Amy H.] Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program,Dept Hlth & Human Serv, Med Chem Sect,Medicat Discovery Res Branch, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program,Dept Hlth & Human Serv, Psychobiol Sect,Medicat Discovery Res Branch, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov RI Hiranita, Takato/G-6567-2011; OI Katz, Jonathan/0000-0002-1068-1159 FU Intramural NIH HHS NR 43 TC 48 Z9 50 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2009 VL 329 IS 2 BP 677 EP 686 DI 10.1124/jpet.108.145813 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 436VK UT WOS:000265444000031 PM 19228996 ER PT J AU Rothman, RB Dersch, CM Ananthan, S Partilla, JS AF Rothman, Richard B. Dersch, Christina M. Ananthan, Subramaniam Partilla, John S. TI Studies of the Biogenic Amine Transporters. 13. Identification of "Agonist" and "Antagonist" Allosteric Modulators of Amphetamine-Induced Dopamine Release SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GUINEA-PIG BRAIN; SEROTONIN TRANSPORTER; COCAINE ADDICTION; BINDING-SITE; IN-VITRO; INHIBITORS; NOREPINEPHRINE; RECEPTOROME; BENZTROPINE; PAROXETINE AB Recent studies identified novel allosteric modulators of the dopamine (DA) transporter (DAT). N-(Diphenylmethyl)-2-phenyl-4-quinazolinamine (SoRI-9804), N-(2,2-diphenylethyl)-2-phenyl-4-quinazolinamine (SoRI-20040), and N-(3,3-diphenylpropyl)-2-phenyl-4-quinazolinamine (SoRI-20041) partially inhibited [(125)I]3 beta-(4'-iodophenyl)tropan-2 beta-carboxylic acid methyl ester (RTI-55) binding, slowed the dissociation rate of [(125)I]RTI-55 from the DAT, and partially inhibited [(3)H] dopamine uptake. In the present study, we report that SoRI-9804 and SoRI-20040, at doses that do not alter release, partially inhibited D-amphetamine-induced DAT-mediated release of [(3)H]1-methyl-4-phenylpyridinium (MPP(+)) or [(3)H]dopamine from striatal synaptosomes ("DAT-mediated DA release") in a dose-dependent manner. SoRI-20041, which does not alter DAT-mediated DA release measured with [(3)H]DA, reversed the effect of SoRI-20040. SoRI-20040 and SoRI-9804 also partially inhibited DAT-mediated DA release induced by DA or (+/-)-3,4-methylenedioxyamphetamine, demonstrating that the observed partial inhibition is not specific for a particular DAT substrate. SoRI-9804 and SoRI-20040 did not attenuate D-amphetamine-induced release of [(3)H]5-hydroxytryptamine from serotonergic, or [(3)H]MPP(+) from noradrenergic, nerve terminals. Kinetic experiments demonstrated that SoRI-9804, in contrast to cocaine, slowed D-amphetamine-induced release of [(3)H]MPP(+) from dopaminergic nerve terminals without altering the apparent rate constants. The two major findings of this study are 1) the identification of both "agonist" (SoRI-9804 and SoRI-20040) and "antagonist" (SoRI-20041) allosteric modulators of D-amphetamine-induced DAT-mediated DA release and 2) [(3)H]DA uptake and D-amphetamine-induced DAT-mediated efflux can be separately modulated. Such agents may have therapeutic potential for the treatment of stimulant addiction, Parkinson's disease, and other psychiatric disorders. C1 [Rothman, Richard B.; Dersch, Christina M.; Partilla, John S.] Natl Inst Drug Abuse, NIH, Clin Psychopharmacol Sect, Intramural Res Program,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Ananthan, Subramaniam] So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. RP Rothman, RB (reprint author), Natl Inst Drug Abuse, NIH, Clin Psychopharmacol Sect, Intramural Res Program,Dept Hlth & Human Serv, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU National Institutes of Health National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the National Institutes of Health National Institute on Drug Abuse. Article, publication date, and citation information can be found at NR 34 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2009 VL 329 IS 2 BP 718 EP 728 DI 10.1124/jpet.108.149088 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 436VK UT WOS:000265444000035 PM 19244097 ER PT J AU Zolkowska, D Jain, R Rothman, RB Partilla, JS Roth, BL Setola, V Prisinzano, TE Baumann, MH AF Zolkowska, Dorota Jain, Raka Rothman, Richard B. Partilla, John S. Roth, Bryan L. Setola, Vincent Prisinzano, Thomas E. Baumann, Michael H. TI Evidence for the Involvement of Dopamine Transporters in Behavioral Stimulant Effects of Modafinil SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 70th Annual Meeting of the College-of-Problems-on-Drug-Dependence CY JUN 14-19, 2008 CL San Juan, PR SP Coll Problems Drug Dependence ID PROMOTING DRUG MODAFINIL; DOUBLE-BLIND; NOREPINEPHRINE TRANSPORTER; COCAINE DEPENDENCE; NUCLEUS-ACCUMBENS; CONSCIOUS RAT; IN-VITRO; RELEASE; GBR12909; AMPHETAMINE AB Modafinil is prescribed for numerous medical conditions, but the drug's mechanism of action is unclear. Here, we examined the interaction of modafinil with receptors and transporters in vitro and compared pharmacological effects of the drug with those produced by indirect dopamine (DA) agonists 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909) and (+)-methamphetamine ( METH). Modafinil was screened at various receptors and transporters using binding assays. Transporter-mediated uptake and release were examined in rat brain synaptosomes. Effects of modafinil on motor activity and neurochemistry were determined in rats undergoing in vivo microdialysis in nucleus accumbens. Of the receptors and transporters assayed, modafinil displayed measurable potency only at DA transporters (DAT), inhibiting [(3)H] DA uptake, with an IC(50) value of 4.0 mu M. Accordingly, modafinil pretreatment (10 mu M) antagonized METH-induced release of the DAT substrate [(3)H]1-methyl-4-phenylpyridinium. Intravenous modafinil (20 and 60 mg/kg) produced dose-dependent increases in motor activity and extracellular DA, without affecting serotonin (5-HT). Analogous results were observed for GBR12909 (1 and 3 mg/kg), whereas METH (0.3 and 1 mg/kg) increased DA and 5-HT. Locomotor effects of all drugs were positively correlated with dialysate DA (P < 0.001). Interestingly, modafinil pretreatment reduced METH-induced ambulation and DA release. Our data show that modafinil interacts with DAT sites in rat brain, a property shared with agonist medications under investigation for treating cocaine dependence. Nondopaminergic mechanisms may also contribute to the pharmacology of modafinil. Finally, the results suggest that modafinil should be tested as an adjunct for treating METH addiction. C1 [Zolkowska, Dorota; Rothman, Richard B.; Partilla, John S.; Baumann, Michael H.] Natl Inst Drug Abuse, NIH, Intramural Res Program, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. [Zolkowska, Dorota] Med Univ Lublin, Dept Hyg, Lublin, Poland. [Jain, Raka] All India Inst Med Sci, Natl Drug Dependence Ctr, New Delhi 110029, India. [Roth, Bryan L.; Setola, Vincent] Univ N Carolina, Sch Med, Dept Pharmacol Med Chem & Psychiat, Chapel Hill, NC USA. [Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. RP Baumann, MH (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, Clin Psychopharmacol Sect, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA. EM mbaumann@mail.nih.gov RI Roth, Bryan/F-3928-2010; Prisinzano, Thomas/B-7877-2010 NR 40 TC 106 Z9 108 U1 2 U2 11 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2009 VL 329 IS 2 BP 738 EP 746 DI 10.1124/jpet.108.146142 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 436VK UT WOS:000265444000037 PM 19197004 ER PT J AU Tudor-Locke, C Washington, TL Ainsworth, BE Troiano, RP AF Tudor-Locke, Catrine Washington, Tracy L. Ainsworth, Barbara E. Troiano, Richard P. TI Linking the American Time Use Survey (ATUS) and the Compendium of Physical Activities: Methods and Rationale SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE metabolic coding; surveillance; secondary analysis ID CLASSIFICATION; SURVEILLANCE; WEIGHT; SYSTEM AB Background: The 2003 Bureau of Labor Statistics American Time Use Survey (ATUS) contains 438 distinct primary activity variables that can be analyzed with regard to how time is spent by Americans. The Compendium of Physical Activities is used to code physical activities derived from various surveys, logs, diaries, etc to facilitate comparison of coded intensity levels across studies. Methods: This article describes the methods, challenges, and rationale for linking Compendium estimates of physical activity intensity (METs, metabolic equivalents) with all activities reported in the 2003 ATUS. Results: The assigned ATUS intensity levels are not intended to compute the energy costs of physical activity in individuals. Instead, they are intended to be used to identify time spent in activities broadly classified by type and intensity. This function will complement public health surveillance systems and aid in policy and health-promotion activities. For example, at least one of the future projects of this process is the descriptive epidemiology of time spent in common physical activity intensity categories. Conclusions: The process of metabolic coding of the ATUS by linking it with the Compendium of Physical Activities can make important contributions to our understanding of American's time spent in health-related physical activity. C1 [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA 70808 USA. [Washington, Tracy L.; Ainsworth, Barbara E.] Arizona State Univ, Dept Exercise & Wellness, Mesa, AZ 85212 USA. [Washington, Tracy L.] Arizona State Univ, Walking Res Lab, Mesa, AZ 85212 USA. [Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20852 USA. RP Tudor-Locke, C (reprint author), Pennington Biomed Res Ctr, Walking Behav Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. OI Washington, Tracy L./0000-0002-0959-7320; Troiano, Richard/0000-0002-6807-989X NR 17 TC 41 Z9 41 U1 1 U2 8 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD MAY PY 2009 VL 6 IS 3 BP 347 EP 353 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 625XT UT WOS:000279930800011 PM 19564664 ER PT J AU Isaac, JTR Feldmeyer, D AF Isaac, John T. R. Feldmeyer, Dirk TI Mechanisms of neocortical development SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material C1 [Isaac, John T. R.] NINDS, Sect Dev Synapt Plast, NIH, Bethesda, MD 20892 USA. [Feldmeyer, Dirk] Res Ctr Julich, Inst Neurosci & Med, INM 2, D-52425 Julich, Germany. [Feldmeyer, Dirk] Univ Hosp, Rhein Westfal TH Aachen, Dept Psychiat & Psychotherapy, D-52074 Aachen, Germany. RP Isaac, JTR (reprint author), NINDS, Sect Dev Synapt Plast, NIH, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov; d.feldmeyer@fz-juelich.de RI Feldmeyer, Dirk/H-5940-2013 OI Feldmeyer, Dirk/0000-0002-1716-8972 NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY 1 PY 2009 VL 587 IS 9 BP 1871 EP 1872 DI 10.1113/jphysiol.2009.171470 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 439HA UT WOS:000265617000005 PM 19406884 ER PT J AU Johann, DJ Rodriguez-Canales, J Mukherjee, S Prieto, DA Hanson, JC Emmert-Buck, M Blonder, J AF Johann, Donald J., Jr. Rodriguez-Canales, Jaime Mukherjee, Sumana Prieto, DaRue A. Hanson, Jeffrey C. Emmert-Buck, Michael Blonder, Josip TI Approaching Solid Tumor Heterogeneity on a Cellular Basis by Tissue Proteomics Using Laser Capture Microdissection and Biological Mass Spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE laser capture microdissection (LCM); mass spectrometry (MS); solid tumor heterogeneity ID EARLY BREAST-CANCER; LIQUID-CHROMATOGRAPHY; PREDICTIVE-VALUE; E-CADHERIN; EXPRESSION; GENE; CELLS; CARCINOMA; ADENOCARCINOMA; CHEMOTHERAPY AB The purpose of this study was to examine solid tumor heterogeneity on a cellular basis using tissue proteomics that relies on a functional relationship between Laser Capture Microdissection (LCM) and biological mass spectrometry (MS). With the use of LCM, homogeneous regions of cells exhibiting uniform histology were isolated and captured from fresh frozen tissue specimens, which were obtained from a human lymph node containing breast carcinoma metastasis. Six specimens similar to 50 000 cell each (three from tumor proper and three from tumor stroma) were collected by LCM. Specimens were processed directly on LCM caps, using sonication in buffered methanol to lyse captured cells, solubilize, and digest extracted proteins. Prepared samples were analyzed by LC/MS/MS resulting in more than 500 unique protein identifications. Decoy database searching revealed a false-positive rate between 5 and 10%. Subcellular localization analysis for stromal cells revealed plasma membrane 14%, cytoplasm 39%, nucleus 11%, extracellular space 27%, and unknown 9%; and tumor cell results were 5%, 58%, 26%, 4%, and 7%, respectively. Western blot analysis confirmed specific linkage of validated proteins to underlying pathology and their potential role in solid tumor heterogeneity. With continued research and optimization of this method including analysis of additional clinical specimens, this approach may lead to an improved understanding of tumor heterogeneity, and serve as a platform for solid tumor biomarker discovery. C1 [Prieto, DaRue A.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. [Johann, Donald J., Jr.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rodriguez-Canales, Jaime; Hanson, Jeffrey C.; Emmert-Buck, Michael] NCI, Laser Microdissect Core Facil, Pathol Lab, Bethesda, MD 20892 USA. [Mukherjee, Sumana; Emmert-Buck, Michael] NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. RP Blonder, J (reprint author), NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. EM blonder@ncifcrf.gov OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [ZIA BC011226-01, Z99 CA999999]; NCI NIH HHS [HHSN261200800001E] NR 37 TC 46 Z9 46 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD MAY PY 2009 VL 8 IS 5 BP 2310 EP 2318 DI 10.1021/pr8009403 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441BW UT WOS:000265745300018 PM 19284784 ER PT J AU Kalish, H Phillips, TM AF Kalish, Heather Phillips, Terry M. TI Application of immunoaffinity capillary electrophoresis to the measurements of secreted cytokines by cultured astrocytes SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Astrocytes; CE; Chemokines; Cytokines; Immunoaffinity ID VASOACTIVE-INTESTINAL-PEPTIDE; MEMORY T-CELLS; BODY-FLUIDS; EXPRESSION; ARRAY; CHIP; NEUROPROTECTION; ASTROGLIA; GAMMA; CSF AB The ability of the central nervous system (CNS) to act in conjunction with the immune system has been of great interest to both neurobiologists and immunologists. Previous studies have shown that astrocytes can be stimulated, by various peptides, to act as immune regulators within the CNS and release cytokines and chemokines. However, the regulatory mechanism of astrocytes is still poorly understood. Our present study describes a micro-device capable of monitoring the growth and stimulation of 20 astrocytes by vasoactive intestinal peptide. A microdialysis needle was used to collect the secretion by products, which were analyzed by immunoaffinity capillary electrophoresis (ICE) for the secretion of pro-inflammatory cytokines, IL-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha; hemopoetic cytokines, IL-3, granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF); and chemokines; regulated upon activation normal T-cell expression Sequence (RANTES), macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta. Vasoactive intestinal peptide stimulated astrocytes showed an almost immediate release of pro-inflammatory cytokines and chemokines, with an increase over baseline ranging from 3 to 15 fold, while no substantial increase over baseline was observed for hemopoetic cytokines. This system demonstrates the ability to isolate individual cells in a closely controlled environment and identify and quantify their analytes. C1 [Kalish, Heather; Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Sect, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. RP Kalish, H (reprint author), Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Sect, Lab Bioengn & Phys Sci, NIH, Bldg 13,Room 3E42,9000 Rockville Pike, Bethesda, MD USA. EM kalishH@mail.nih.gov FU National Institute of Biomedical Imaging and Bioengineering, NIH FX This research was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, NIH. NR 44 TC 12 Z9 12 U1 2 U2 14 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD MAY PY 2009 VL 32 IS 10 BP 1605 EP 1612 DI 10.1002/jssc.200900047 PG 8 WC Chemistry, Analytical SC Chemistry GA 451ZF UT WOS:000266508700011 PM 19472286 ER PT J AU Yu, EH Lungu, C Kanner, RM Libman, RB AF Yu, Edward Haosheng Lungu, Codrin Kanner, Ronald M. Libman, Richard Benjamin TI The Use of Diagnostic Tests in Patients with Acute Ischemic Stroke SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Cerebral ischemic stroke; diagnostic test assessment; ultrasound; echocardiography; Holter; magnetic resonance imaging; decision analysis ID PATENT FORAMEN-OVALE; SYMPTOMATIC CAROTID STENOSIS; PAROXYSMAL ATRIAL-FIBRILLATION; AMERICAN-HEART-ASSOCIATION; ACADEMY-OF-NEUROLOGY; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANSTHORACIC ECHOCARDIOGRAPHY; CEREBROVASCULAR EVENTS; RECURRENT STROKE; ARTERY-STENOSIS AB Background: Stroke is a leading cause of long-term disability in the United States. Inpatient hospital costs account for the majority of acute care costs of stroke with half the cost providing for room and board and 19% of total costs allocated to diagnostic testing. This study addresses the yield of common diagnostic tests in stroke and how frequently the results potentially impact early stroke management. Methods: We conducted a retrospective chart review of patients with acute ischemic stroke over 3 years from a single-center community-based teaching hospital. Results of carotid Doppler (CD), transcranial Doppler, extracranial magnetic resonance (MR) angiography (EMRA), intracranial MR angiography, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and 24-hour Holter monitoring were reviewed. Results: Extracranial carotid artery imaging with CD and EMRA showed symptomatic ipsilateral stenosis in 7.9% and 13% of patients with stroke. TTE alone showed intracardiac thrombus in 1.5% of patients whereas TEE had a yield of 3.8%. Patent foramen ovale was seen in 16% of TEE and none were detected on TTE. The 24-hour Holter monitoring revealed newly detected atrial fibrillation in 9.4% of patients with stroke. Conclusions: Standard diagnostic studies in acute stroke aimed at secondary stroke prevention are unlikely to yield results that warrant prolongation of hospitalization. Carotid endarterectomy is the only intervention with reasonable evidence suggesting benefit in the early period after stroke. Pursuing extracranial carotid artery imaging during initial hospitalization seems justifiable, especially given the high yield of CD and EMRA in the detection of treatable carotid artery stenosis. C1 [Yu, Edward Haosheng; Lungu, Codrin; Kanner, Ronald M.; Libman, Richard Benjamin] N Shore Long Isl Jewish Hlth Syst, Dept Neurol, New Hyde Pk, NY USA. [Yu, Edward Haosheng] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Lungu, Codrin] NINDS, NIH, Bethesda, MD 20892 USA. RP Libman, RB (reprint author), Long Isl Jewish Med Ctr, Div Vasc Neurol, 270-05 76 Ave, New Hyde Pk, NY 11040 USA. EM RLibman@lij.edu NR 45 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD MAY-JUN PY 2009 VL 18 IS 3 BP 178 EP 184 DI 10.1016/j.jstrokecerebrovasdis.2008.09.004 PG 7 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 448XH UT WOS:000266294800002 PM 19426886 ER PT J AU Henry, LR Stojadinovic, A Swain, SM Prindiville, S Cordes, R Soballe, PW AF Henry, Leonard R. Stojadinovic, Alexander Swain, Sandra M. Prindiville, Sheila Cordes, Rose Soballe, Peter W. TI The Influence of a Gene Expression Profile on Breast Cancer Decisions SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE breast cancer; recurrence score; adjuvant therapy ID RT-PCR ASSAY; ADJUVANT CHEMOTHERAPY; ECONOMIC-ANALYSIS; THERAPY; WOMEN; COST AB Purpose: The Oncotype Dx (R) Recurrence Score (RS), is often employed in patients with estrogen receptor-positive, node negative (ER+LN-) breast cancer. We investigated the impact of the RS on actual chemotherapy administration and the effect of the assay on a panel of breast oncology experts. Patients and Methods: The prospective adjuvant chemotherapy recommendations (prior to RS) and actual adjuvant therapy (after RS) for consecutive patients with ER+LN- breast cancer were recorded. After 6 months and with the same information, a panel of five experts made adjuvant therapy recommendations with and without RS and rated the strength of their recommendations. Rates of panel consensus, recommendation changes, and changes in recommendation strength were compared. Results: There were 29 patients (28 women). RS results altered the plan for chemotherapy in 9 patients (31%): 7 of 13 patients (54%) initially recommended for chemotherapy did not receive it, and 2 of 16 (13%) received chemotherapy following initial recommendations against it. RS results changed the panel's chemotherapy recommendation in 7 patients (24%): 5 of 12( 42%) recommendations for changed to against, and 2 of 17 (12%) recommendations against changed to for chemotherapy. RS increased consensus by the panel 10%, but did not increase the reported strength in chemotherapy recommendations. Conclusions: RS results were associated with real-world decision changes in 31% of patients and 24% of panel recommendations and increased panel consensus by 10%. However RS did not increase the strength of penelist's recommendations. J. Surg. Oncol. 2009:99: 319-323. Published 2009 Wiley-liss, Inc. C1 [Henry, Leonard R.] Natl Naval Med Ctr, Dept Surg, Div Surg Oncol, Bethesda, MD USA. [Stojadinovic, Alexander] Walter Reed Army Med Ctr, Dept Surg, Div Surg Oncol, Washington, DC 20307 USA. [Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Dept Med Oncol, Washington, DC 20010 USA. [Prindiville, Sheila] NCI, Dept Genet, Bethesda, MD 20892 USA. [Cordes, Rose] Natl Naval Med Ctr, Natl Capital Area Breast Care Ctr, Bethesda, MD USA. [Henry, Leonard R.; Stojadinovic, Alexander; Soballe, Peter W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Henry, LR (reprint author), 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM leonard.henry@med.navy.mil OI Swain, Sandra/0000-0002-1320-3830 NR 18 TC 54 Z9 55 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD MAY 1 PY 2009 VL 99 IS 6 BP 319 EP 323 DI 10.1002/jso.21244 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA 438HE UT WOS:000265545700001 PM 19204954 ER PT J AU Giedd, JN Lalonde, FM Celano, MJ White, SL Wallace, GL Lee, NR Lenroot, RK AF Giedd, Jay N. Lalonde, Francois M. Celano, Mark J. White, Samantha L. Wallace, Gregory L. Lee, Nancy R. Lenroot, Rhoshel K. TI Anatomical Brain Magnetic Resonance Imaging of Typically Developing Children and Adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID SEXUAL-DIMORPHISM; CORTICAL DEVELOPMENT; IN-VIVO; CHILDHOOD; GROWTH; MULTIVARIATE; MATURATION; THICKNESS; CORTEX; AGE C1 [Giedd, Jay N.; Lalonde, Francois M.; Celano, Mark J.; White, Samantha L.; Wallace, Gregory L.; Lee, Nancy R.; Lenroot, Rhoshel K.] NIMH, Child Psychiat Branch, Bethesda, MD 20854 USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr, Bethesda, MD 20854 USA. EM jg@nih.gov RI Lee, Nancy Raitano/F-2565-2011; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713; Wallace, Gregory/0000-0003-0329-5054 FU Intramural NIH HHS [ZIA MH002794-08] NR 20 TC 127 Z9 128 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2009 VL 48 IS 5 BP 465 EP 470 DI 10.1097/CHI.0b013e31819f2715 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 437BO UT WOS:000265461000003 PM 19395901 ER PT J AU Wu, LT Ringwalt, CL Yang, CM Reeve, BB Pan, JJ Blazer, DG AF Wu, Li-Tzy Ringwalt, Christopher L. Yang, Chongming Reeve, Bryce B. Pan, Jeng-Jong Blazer, Dan G. TI Construct and Differential Item Functioning in the Assessment of Prescription Opioid Use Disorders Among American Adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE DSM-IV; item response theory; nosology; opioid use disorders ID RESPONSE THEORY ANALYSIS; NATIONAL EPIDEMIOLOGIC SURVEY; DSM-V; ALCOHOL DEPENDENCE; SCHOOL-DISTRICT; DRUG-ABUSE; CANNABIS; CRITERIA AB Objective: To examine the psychometric properties of diagnostic criteria for prescription analgesic opioid use disorders (OUDs) and to identify background predictors of a latent continuum for OUD liability. Method: Data were drawn from the adolescent sample of the 2006 National Survey of Drug Use and Health. Item response theory (IRT) and multiple indicators-multiple causes methods were used to examine DSM-IV criteria for OUDs in a subsample of adolescents who reported nonmedical prescription opioid use in the past year (N=1,290). Results: Among nonmedical users of prescription opioids, the criteria of OUDs were arrayed along a single continuum of severity. All abuse criteria were endorsed at a severity level higher than D1 (tolerance) and D5 (time spent) but lower than D3 (taking larger amounts) and D4 (inability to cut down). Differential item functioning in reports of dependence symptoms across adolescents' sex and race/ethnicity were identified: withdrawal, time spent, and continued use despite medical or psychological problems. Adjusting for the effects of differential item functioning and the demographic variables examined, female subjects were more likely than male subjects to exhibit a higher level of OUD liability. Conclusions: Study findings do not support the DSM-IVs current hierarchical distinction between abuse of and dependence on prescription opioids. Abuse symptoms in adolescents are not necessarily less severe than those of dependence. There is evidence of some differential item functioning in the assessment of OUDs. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(5):563-572. C1 [Wu, Li-Tzy; Blazer, Dan G.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27710 USA. [Yang, Chongming] Duke Univ, Social Sci Res Inst, Durham, NC 27710 USA. [Reeve, Bryce B.] NCI, Bethesda, MD 20892 USA. RP Wu, LT (reprint author), Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Med Ctr, Box 3419, Durham, NC 27710 USA. EM litzywu@yahoo.com FU U. S. National Institute on Drug Abuse of the National Institutes of Health [DA019623, DA019901] FX This work was supported by research grants front the U. S. National Institute on Drug Abuse of the National Institutes of Health to Dr. Wu (DA019623 and DA019901). The Substance Abuse and Mental Health Data Archive and the Inter-university Consortium for Political and Social Research provided the public use data files for National Surrey on Drug Use and Health, which was sponsored by the Office of Applied Studies of the Substance Abuse and Mental Health Services Administration. The opinions expressed in this article are solely those of the authors and not of any sponsoring agency. NR 31 TC 16 Z9 16 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 2009 VL 48 IS 5 BP 563 EP 572 DI 10.1097/CHI.0b013e31819e3f45 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 437BO UT WOS:000265461000013 PM 19318987 ER PT J AU Gozalo, AS Rosenberg, HF Elkins, WR Montoya, EJ Weller, RE AF Gozalo, Alfonso S. Rosenberg, Helene F. Elkins, William R. Montoya, Enrique J. Weller, Richard E. TI Multisystemic Eosinophilia Resembling Hypereosinophilic Syndrome in a Colony-Bred Owl Monkey (Aotus vociferans) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID DISORDERS; THERAPY; DISEASE; EVOLUTION; IMATINIB; GENES; CATS AB In animals, multisystemic eosinophilic disease is a rare condition characterized by eosinophilic and lymphoplasmacytic infiltrates in various organs. This disorder resembles the human disease known as hypereosinophilic syndrome, a condition defined by prolonged peripheral eosinophilia in the absence of recognizable etiology and associated with end-organ damage. In this report we describe a research-naive, colony-born, juvenile female owl monkey (Aotus vociferans) who presented clinically with severe respiratory distress and histologically with multiple end-organ infiltration with phenotypically mature eosinophils, plasma cells, and lymphocytes. No tumors or infectious agents were noted either macroscopically or microscopically. Cultures from lung samples revealed no bacteria or fungi. Histologic examination of lung, heart, thymus, liver, spleen, kidney, adrenal, pancreas, stomach, small intestine, and colon revealed no migrating nematode larvae, other parasites, or foreign material that might trigger eosinophilia, nor was there any evidence of or history consistent with an allergic etiology. Given that we ruled out most exogenous and endogenous triggers of eosinophilia, the signs, symptoms, and pathologic findings support the diagnosis of multisystemic eosinophilic disease. To our knowledge, this report is the first description of presumptive hypereosinophilic syndrome in a nonhuman primate. C1 [Gozalo, Alfonso S.; Elkins, William R.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Rosenberg, Helene F.] NIAID, Eosinophil Biol Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Gozalo, Alfonso S.] SoBran, Bethesda, MD USA. [Montoya, Enrique J.] Univ Nacl Mayor San Marcos, Fac Med Vet, Vet Invest Trop & Altura, Iquitos, Peru. [Weller, Richard E.] Pacific NW Natl Lab, Richland, WA 99352 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Peruvian Government; Pan American Health Organization [ICF-/ZNS/010]; National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID); Comparative Medicine Branch; Office of Research Support FX This Study was conducted as part of the activities of the Peruvian Primatological Project, Supported by the Peruvian Government and the Pan American Health Organization (ICF-/ZNS/010), and by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), Comparative Medicine Branch, the Office of Research Support, and a NIAID contract to SoBran. We thank Dr Carmen Michaud for photographic assistance. NR 23 TC 3 Z9 3 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAY PY 2009 VL 48 IS 3 BP 303 EP 306 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 450HV UT WOS:000266392500011 PM 19476722 ER PT J AU Stewart, RM Park, PK Hunt, JP McIntyre, RC McCarthy, J Zarzabal, LA Michalek, JE AF Stewart, Ronald M. Park, Pauline K. Hunt, John P. McIntyre, Robert C., Jr. McCarthy, Janet Zarzabal, Lee Ann Michalek, Joel E. CA NIH NHLBI ARDS Clinical Trials TI Less Is More: Improved Outcomes in Surgical Patients with Conservative Fluid Administration and Central Venous Catheter Monitoring SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 120th Annual Meeting of the Southern-Surgical-Association CY DEC, 2008 CL Palm Beach, FL SP SE Surg Assoc ID PULMONARY-ARTERY CATHETERIZATION; RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; CRITICALLY ILL PATIENTS; SHOCK RESUSCITATION; HEMORRHAGIC-SHOCK; IMPROVED SURVIVAL; MESENTERIC LYMPH; CLINICAL-TRIALS; TRAUMA AB BACKGROUND: The ARDS Clinical Trials Network Fluid and Catheter Treatment Trial (FACTT) addressed fluid management and central monitoring of patients with acute respiratory distress syndrome/acute lung injury (ARDS/ALI). Because Surgical patients may have been fundamentally different from the overall FACTT cohort, We Set Out to separately analyze the surgery patients in the trial. STUDY DESIGN: We performed a posthoc, surgical Subgroup analysis of 1,000 patients enrolled in the FACTT. Patients were randomized using a 2 X 2 factorial design comparing a conservative (CON) versus a liberal (LIB) strategy Of fluid management and the use of a Pulmonary artery cartheter (PAC) or a central venous catheter (CVC). The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days, ICU-free clays, and dialysis-free days until hospital discharge Lip to day 90. We defined Surgical patients as those admitted to a surgical ICU, burn ICU, or cardiac Surgical ICU; trauma patients; or those with an APACHE III Surgical admission type. RESULTS: There were 244 surgical patients. Risk of death within 60 days of randomization did not vary with catheter or fluid management, and a corresponding lack of effect was evident with regard to dialysis-free days. Ventilator-free days were increased in the fluid-conservative group (LIB, 13 +/- 1 days; CON, 15 +/- 1 days; p = 0.04) at 28 days. CVC patients had more ventilator-free days at 28 and 90 days (28 days: CVC, 16 +/- 1 days; PAC, 13 +/- 1 days; p = 0.03; 90 days: CVC, 64 +/- 3 days; PAC, 57 +/- 4 days; p = 0.03). CVC patients had more ICU-free days at 90 days (90 days: CVC, 63 +/- 3 days; PAC, 55 +/- 3 days; p = 0.04). CONCLUSIONS: The risk of death did not vary with fluid management or catheter. A conservative fluid-administration strategy and central venous catheter monitoring resulted in more ventilator-free and ICU-free days In surgical patients with acute lung injury, and conservative fluid administration did not result in more renal failure. (J Am Coll Surg 2009;208:725-737. (C) 2009 by the American College Of Surgeons) C1 [Stewart, Ronald M.; McCarthy, Janet; Zarzabal, Lee Ann] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA. [Park, Pauline K.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hunt, John P.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [McCarthy, Janet] Univ Colorado, Denver, CO 80202 USA. [Michalek, Joel E.] NHLBI, NIH, Acute Resp Distress Syndrome Clin Trials Network, Bethesda, MD 20892 USA. RP Stewart, RM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [N01-HR-16146-54, N01-HR-46054-64] NR 37 TC 62 Z9 72 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2009 VL 208 IS 5 BP 725 EP 735 DI 10.1016/j.jamcollsurg.2009.01.026 PG 11 WC Surgery SC Surgery GA 441WP UT WOS:000265801500016 PM 19476825 ER PT J AU Patel, CO Cimino, JJ AF Patel, Chintan O. Cimino, James J. TI Using Semantic and Structural Properties of the Unified Medical Language System to Discover Potential Terminological Relationships SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium on American-Medical-Informatics-Association CY NOV 08-12, 2008 CL Washington, DC SP Amer Med Informat Assoc ID NETWORK AB Objective: To use the semantic and structural properties in the Unified Medical Language System (UMLS) Metathesaurus to characterize and discover potential relationships. Design: The UMLS integrates knowledge from several biomedical terminologies. This knowledge call be used to discover implicit semantic relationships between concepts. In this paper, the authors propose a problem-independent approach for discovering potential terminological relationships that employs semantic abstraction of indirect relationship paths to perform classification and analysis of network theoretical measures Such as topological overlap, preferential attachment, graph partitioning, and number of indirect paths. Using different versions of the UMLS, the authors evaluate the proposed approach's ability to predict newly added relationships. Measurements: Classification accuracy, precision-recall. Results: Strong discriminative characteristics were observed with a semantic abstraction based classifier (classification accuracy of 91%), the average number of indirect paths, preferential attachment, and graph partitioning to identify potential relationships. The proposed relationship prediction algorithm resulted in 56% recall in top 10 results for new relationships added to subsequent versions of the UMLS between 2005 and 2007. Conclusions: The UMLS has sufficient knowledge to enable discovery of potential terminological relationships. J Am Med Inform Assoc. 2009;16:346-353. DOI 10.1197/jamia.M2931. C1 [Patel, Chintan O.] Columbia Univ, Dept Biomed Informat, Vanderbilt Clin, New York, NY 10032 USA. [Cimino, James J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Patel, CO (reprint author), Columbia Univ, Dept Biomed Informat, Vanderbilt Clin, 5th Floor,622 W 168th St, New York, NY 10032 USA. EM chintan.patel@dbmi.columbia.edu OI Cimino, James/0000-0003-4101-1622 FU Intramural NIH HHS; NLM NIH HHS [R21 LM009638, R21LM009638] NR 21 TC 5 Z9 5 U1 0 U2 1 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2009 VL 16 IS 3 BP 346 EP 353 DI 10.1197/jamia.M2931 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 447DU UT WOS:000266172600014 PM 19261940 ER PT J AU Ohno-Machado, L Ellison, D Shortliffe, EH AF Ohno-Machado, Lucila Ellison, Donald Shortliffe, Edward H. TI Presentation of the 2008 Morris F. Collen Award to Robert A. Greenes SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Biographical-Item C1 [Ohno-Machado, Lucila] Harvard Univ, Decis Syst Grp, Brigham & Womens Hosp, Sch Med, Boston, MA 02215 USA. [Ellison, Donald] Natl Lib Med, Bethesda, MD USA. [Shortliffe, Edward H.] Arizona State Univ, Phoenix, AZ USA. [Shortliffe, Edward H.] Amer Med Informat Assoc, Bethesda, MD USA. RP Ohno-Machado, L (reprint author), Harvard Univ, Decis Syst Grp, Brigham & Womens Hosp, Sch Med, 900 Commonwealth Ave, Boston, MA 02215 USA. EM machado@dsg.harvard.edu OI Ohno-Machado, Lucila/0000-0002-8005-7327 FU NLM NIH HHS [T15 LM007092] NR 1 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAY-JUN PY 2009 VL 16 IS 3 BP 413 EP 418 DI 10.1197/jamia.M3172 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 447DU UT WOS:000266172600024 PM 19606540 ER PT J AU Flowers, L Wick, J Figg, WD McClelland, RH Shiber, M Britton, JE Ngo, DKH Borders-Hemphill, V Mead, C Zee, J Huntzinger, P AF Flowers, Louis Wick, Jeannette Figg, William Douglas, Sr. McClelland, Robert H. Shiber, Michael Britton, James E. Ngo, Diem-Kieu H. Borders-Hemphill, Vicky Mead, Christina Zee, Jerry Huntzinger, Paul TI US Public Health Service Commissioned Corps pharmacists: Making a difference in advancing the nation's health SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Federal pharmacy; US Public Health Service; Commissioned Corps officers; US Department of Health and Human Services AB Objective: To describe how U. S. Public Health Service (PHS) pharmacists serving in jobs that are normal for them, but considerably different than those found in the private sector, are making a difference in advancing the nation's health. Summary: Pharmacists who serve in the Commissioned Corps of PHS fill roles that are considerably different than their counterparts in the private sector. Their work takes them out from behind the counter and into the world. Pharmacy officers advance the health and safety of the nation by their involvement in the delivery of direct patient care to medically underserved people, national security, drug vigilance, research, and policy-making endeavors. PHS pharmacists fill essential public health leadership and service roles throughout the U. S. Department of Health and Human Services (HHS) and certain non-HHS federal agencies and programs. The Health Resources and Services Administration, National Institutes of Health, Federal Bureau of Prisons, Indian Health Service, Food and Drug Administration, and U. S. Coast Guard are among the many federal agencies in which pharmacy officers are assigned. Conclusion: In each setting, PHS pharmacists find traditional roles augmented with assignments and challenges that broaden the scope of their practice. C1 [Flowers, Louis] US FDA, Div Training & Dev, Off Training & Commun, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Wick, Jeannette] NCI, Pharmaceut Management Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. [Figg, William Douglas, Sr.] NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Figg, William Douglas, Sr.] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [McClelland, Robert H.] Indian Hlth Serv, Elko, NV USA. [Shiber, Michael] Fed Bur Prisons, Washington, DC USA. [Britton, James E.] Fed Bur Prisons Natl HIV Clin Consultant Pharmaci, Springfield, MO USA. [Ngo, Diem-Kieu H.] US FDA, Off Execut Programs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Mead, Christina] Indian Hlth Serv, Bloomfield, NM USA. [Zee, Jerry] Indian Hlth Serv, Omak Satellite Clin, Omak, WA USA. [Huntzinger, Paul] US Coast Guard Integrated Support Command Pharm, Alameda, CA USA. RP Flowers, L (reprint author), DTD OTCOM CDER FDA, Bldg 51,Room 2316,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM louis.flowers@fda.hhs.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [Z99 CA999999] NR 25 TC 3 Z9 3 U1 0 U2 3 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD MAY-JUN PY 2009 VL 49 IS 3 BP 446 EP 452 DI 10.1331/JAPhA.2009.08036 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 453LU UT WOS:000266612800016 PM 19443327 ER PT J AU Najjar, SS AF Najjar, Samer S. TI IMT as a Risk Marker: The Plot Thickens SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID INTIMA-MEDIA THICKNESS; ARTERIAL-WALL; VASCULAR MEDICINE; AMERICAN SOCIETY; ATHEROSCLEROSIS; ULTRASOUND; HYPERTENSION; DISEASE; ECHOCARDIOGRAPHY; METAANALYSIS C1 [Najjar, Samer S.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Najjar, SS (reprint author), Harbor Hosp, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA. EM najjarsa@mail.nih.gov FU Intramural NIH HHS [Z01 AG000856-06] NR 23 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2009 VL 22 IS 5 BP 505 EP 507 DI 10.1016/j.echo.2009.03.019 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 446AA UT WOS:000266091400014 PM 19450743 ER PT J AU Madero, M Wassel, CL Peralta, CA Najjar, SS Sutton-Tyrrell, K Fried, L Canada, R Newman, A Shlipak, MG Sarnak, MJ AF Madero, Magdalena Wassel, Christina L. Peralta, Carmen A. Najjar, Samer S. Sutton-Tyrrell, Kim Fried, Linda Canada, Robert Newman, Anne Shlipak, Michael G. Sarnak, Mark J. CA Health ABC Study TI Cystatin C Associates with Arterial Stiffness in Older Adults SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Nephrology/Annual Renal Week CY NOV 14-19, 2006 CL San Diego, CA SP Amer Soc Nephrol ID PULSE-WAVE VELOCITY; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR EVENTS; RISK-FACTOR; CREATININE CLEARANCE; AORTIC STIFFNESS; MORTALITY; PRESSURE AB Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR <60 ml/min per 1.73 m(2), did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults. C1 [Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA. [Madero, Magdalena] Inst Nacl Cardiol Ignacio Chavez Mexico City, Dept Nephrol, Mexico City, DF, Mexico. [Wassel, Christina L.; Peralta, Carmen A.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Wassel, Christina L.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Wassel, Christina L.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. [Najjar, Samer S.] NIA, NIH, Bethesda, MD 20892 USA. [Sutton-Tyrrell, Kim; Newman, Anne] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. [Fried, Linda] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. [Canada, Robert] Univ Tennessee, Hlth Sci Ctr, Memphis, TN 38163 USA. RP Sarnak, MJ (reprint author), Tufts Med Ctr, Div Nephrol, Dept Med, Box 391,800 Washington St, Boston, MA 02111 USA. EM msarnak@tuftsmedicalcenter.org RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [K24 DK078204] NR 34 TC 34 Z9 37 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2009 VL 20 IS 5 BP 1086 EP 1093 DI 10.1681/ASN.2008030318 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 444DE UT WOS:000265959800022 PM 19357259 ER PT J AU West, M Nicholls, K Mehta, A Clarke, JTR Steiner, R Beck, M Barshop, BA Rhead, W Mensah, R Ries, M Schiffmann, R AF West, Michael Nicholls, Kathy Mehta, Atul Clarke, Joe T. R. Steiner, Robert Beck, Michael Barshop, Bruce A. Rhead, William Mensah, Robert Ries, Markus Schiffmann, Raphael TI Agalsidase Alfa and Kidney Dysfunction in Fabry Disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ENZYME REPLACEMENT THERAPY; RENAL-FUNCTION; CLINICAL MANIFESTATIONS; BETA THERAPY; GALACTOSIDASE; SAFETY; TRIAL; PREVALENCE; MUTATIONS; EFFICACY AB In male patients with Fabry disease, an X-linked disorder of glycosphingolipid metabolism caused by deficient activity of the lysosomal enzyme alpha-galactosidase A, kidney dysfunction becomes apparent by the third decade of life and invariably progresses to ESRD without treatment. Here, we summarize the effects of agalsidase alfa on kidney function from three prospective, randomized, placebo-controlled trials and their open-label extension studies involving 108 adult male patients. The mean baseline GFR among 54 nonhyperfiltrating patients (measured GFR < 135 ml/min per 1.73 m(2)) treated with placebo was 85.4 +/- 29.6 ml/min per 1.73 m(2); during 6 mo of placebo, the mean annualized rate of change in GFR was -7.0 +/- 32.9 ml/min per 1.73 m(2). Among 85 nonhyperfiltrating patients treated with agalsidase alfa, the annualized rate of change was -2.9 +/- 8.7 ml/min per 1.73 m(2). Treatment with agalsidase alfa did not affect proteinuria. Multivariate analysis revealed that GFR and proteinuria category (< 1 or >= 1 g/d) at baseline significantly predicted the rate of decline of GFR during treatment. This summary represents the largest group of male patients who had Fabry disease and for whom the effects of enzyme replacement therapy on kidney function have been studied. These data suggest that agalsidase alfa may stabilize kidney function in these patients. C1 [West, Michael] Dalhousie Univ, Div Nephrol, Dept Med, Halifax, NS B3H 1V8, Canada. [Nicholls, Kathy] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Mehta, Atul] Royal Free & Univ Coll Med Sch, London WC1E 6BT, England. [Clarke, Joe T. R.] Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Clarke, Joe T. R.] Univ Toronto, Toronto, ON, Canada. [Clarke, Joe T. R.] CHU Sherbrooke, Serv Genet Med, Sherbrooke, PQ J1H 5N4, Canada. [Steiner, Robert] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Beck, Michael; Ries, Markus] Johannes Gutenberg Univ Mainz, Ctr Lysosomal Storage Dis, Mainz, Germany. [Barshop, Bruce A.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Rhead, William] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Mensah, Robert] Shire HGT, Cambridge, MA USA. [Ries, Markus; Schiffmann, Raphael] NINCDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP West, M (reprint author), Dalhousie Univ, Div Nephrol, Dept Med, 5090 ACC QE 2 Hlth Sci Ctr,5820 Univ Ave, Halifax, NS B3H 1V8, Canada. EM mlwest@dal.ca OI Steiner, Robert/0000-0003-4177-4590; Ries, Markus/0000-0002-5054-5741 FU Shire Human Genetic Therapies (formerly TKT); Genzyme; Amicus Therapeutics; Shire Human Genetic Therapies; Actelion; Biomarin; Hyperion; Ucyclyd FX Raphael Schiffmarm has received research funding, consultancy fees, and/or speaker's fees from Shire Human Genetic Therapies, Genzyme, and Amicus Therapeutics. NR 31 TC 94 Z9 103 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2009 VL 20 IS 5 BP 1132 EP 1139 DI 10.1681/ASN.2008080870 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 444DE UT WOS:000265959800027 PM 19357250 ER PT J AU Grubb, RL Black, A AF Grubb, Robert L., III Black, Amanda TI Yearly Prostate Specific Antigen and Digital Rectal Examination Fluctuations in a Screened Population COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Grubb, Robert L., III] Washington Univ, Sch Med, Dept Surg, Div Urol, St Louis, MO 63110 USA. [Black, Amanda] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD USA. RP Grubb, RL (reprint author), Washington Univ, Sch Med, Dept Surg, Div Urol, St Louis, MO 63110 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2009 VL 181 IS 5 BP 2076 EP 2076 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 431PJ UT WOS:000265074800030 ER PT J AU Chen, Q Espey, MG Sun, AY Pooput, C Kirk, KL Krishna, MC Khosh, DB Drisko, J Levine, M AF Chen, Q. Espey, M. G. Sun, A. Y. Pooput, C. Kirk, K. L. Krishna, M. C. Khosh, D. B. Drisko, J. Levine, M. TI Pharmacologic Doses of Ascorbate Act as a Prooxidant and Decrease Growth of Aggressive Tumor Xenografts in Mice Editorial Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Chen, Q.] NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Chen, Q (reprint author), NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2009 VL 181 IS 5 BP 2384 EP 2385 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 431PJ UT WOS:000265074800150 ER PT J AU Rotman, Y Katz, L Cohen, M Cohen-Ezra, O Manhaim, V Braun, M Ben-Ari, Z Tur-Kaspa, R AF Rotman, Y. Katz, L. Cohen, M. Cohen-Ezra, O. Manhaim, V. Braun, M. Ben-Ari, Z. Tur-Kaspa, R. TI Low weight predicts neutropenia and peginterferon alfa-2a dose reductions during treatment for chronic hepatitis C SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE bone marrow depression; chronic hepatitis C; neutropenia; pegylated interferon alfa-2a; side-effects; weight ID COMBINATION THERAPY; PLUS RIBAVIRIN; PEGYLATED INTERFERONS; ANTIVIRAL THERAPY; MANAGEMENT; INFECTION; COMPLICATIONS; EFFICACY AB Treatment-induced neutropenia frequently complicates the treatment course of patients treated with pegylated interferon alfa and ribavirin for chronic hepatitis C. We investigated the effect of weight on the risk for dose reductions caused by neutropenia in patients treated with a weight-independent dose of peginterferon alfa-2a. We retrospectively analysed single centre data for 172 patients enrolled in a multi-centre, open-label trial of peginterferon alfa-2a and ribavirin for chronic hepatitis C. Low body weight was significantly associated with dose reductions due to neutropenia. Patients weighing less than 62 kg had a 35% risk for significant neutropenia as opposed to a 12% risk for heavier patients (P = 0.001), and this side-effect occurred earlier during treatment. Low weight was an independent risk factor by multivariate analysis (hazard ratio 0.956/kg). The risk for treatment-induced neutropenia was associated with body surface area more than with the body mass index. In conclusion, a low pre-treatment weight strongly predicts the need for peginterferon alfa-2a dose reductions. This apparently reflects overall body size more than body fat content. It is prudent to frequently monitor blood counts for smaller-sized patients, especially during the first weeks of treatment. C1 [Rotman, Y.; Cohen, M.; Cohen-Ezra, O.; Manhaim, V.; Braun, M.; Ben-Ari, Z.; Tur-Kaspa, R.] Beilinson Med Ctr, Rabin Med Ctr, Liver Inst, Petah Tiqwa, Israel. [Rotman, Y.; Cohen, M.] Beilinson Med Ctr, Rabin Med Ctr, Dept Gastroenterol, Petah Tiqwa, Israel. [Katz, L.; Tur-Kaspa, R.] Beilinson Med Ctr, Rabin Med Ctr, Dept Med D, Petah Tiqwa, Israel. [Rotman, Y.; Cohen, M.; Braun, M.; Ben-Ari, Z.; Tur-Kaspa, R.] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Rotman, Y (reprint author), NIDDKD, NIH, Liver Dis Branch, CRC, 10 Ctr Dr,Room 4-5722, Bethesda, MD 20892 USA. EM rotmany@mail.nih.gov NR 24 TC 1 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAY PY 2009 VL 16 IS 5 BP 340 EP 345 DI 10.1111/j.1365-2893.2009.01079.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 426VR UT WOS:000264736900006 PM 19220735 ER PT J AU Zhao, J Lai, LL Amara, RR Montefiori, DC Villinger, F Chennareddi, L Wyatt, LS Moss, B Robinson, HL AF Zhao, Jun Lai, Lilin Amara, Rama Rao Montefiori, David C. Villinger, Francois Chennareddi, Lakshmi Wyatt, Linda S. Moss, Bernard Robinson, Harriet L. TI Preclinical Studies of Human Immunodeficiency Virus/AIDS Vaccines: Inverse Correlation between Avidity of Anti-Env Antibodies and Peak Postchallenge Viremia SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; POLYMERASE CHAIN-REACTION; GM-CSF DNA; HIV TYPE-1; NEUTRALIZING ANTIBODIES; MEDIATED CYTOTOXICITY; RHESUS MACAQUES; DNA/MVA VACCINE; ACUTE-PHASE; T-CELLS AB A major challenge for human immunodeficiency virus (HIV)/AIDS vaccines is the elicitation of anti-Env antibodies (Ab) capable of neutralizing the diversity of isolates in the pandemic. Here, we show that high-avidity, but nonneutralizing, Abs can have an inverse correlation with peak postchallenge viremia for a heterologous challenge. Vaccine studies were conducted in rhesus macaques using DNA priming followed by modified vaccinia Ankara boosting with HIV type 1 (HIV-1) immunogens that express virus-like particles displaying CCR5-tropic clade B (strain ADA) or clade C (IN98012) Envs. Rhesus granulocyte-macrophage colony-stimulating factor was used as an adjuvant for enhancing the avidity of anti-Env Ab responses. Challenge was with simian/human immunodeficiency virus (SHIV)-162P3, a CCR5-tropic clade B chimera of SIV and HIV-1. Within the groups receiving the clade B vaccine, a strong inverse correlation was found between the avidity of anti-Env Abs and peak postchallenge viremia. This correlation required the use of native but not gp120 or gp140 forms of Env for avidity assays. The high-avidity Ab elicited by the ADA Env had excellent breadth for the Envs of incident clade B but not clade C isolates, whereas the high-avidity Ab elicited by the IN98012 Env had excellent breadth for incident clade C but not clade B isolates. High-avidity Ab elicited by a SHIV vaccine with a dual-tropic clade B Env (89.6) had limited breadth for incident isolates. Our results suggest that certain Envs can elicit nonneutralizing but high-avidity Ab with broad potential for blunting incident infections of the same clade. C1 [Zhao, Jun; Lai, Lilin; Amara, Rama Rao; Chennareddi, Lakshmi; Robinson, Harriet L.] Emory Vaccine Ctr, Atlanta, GA 30329 USA. [Zhao, Jun; Lai, Lilin; Amara, Rama Rao; Villinger, Francois; Chennareddi, Lakshmi; Robinson, Harriet L.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. [Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Villinger, Francois] Emory Clin, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Wyatt, Linda S.; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), GeoVax Inc, 1256 Briarcliff Rd, Atlanta, GA 30306 USA. EM hrobinson@geovax.com FU Integrated Preclinical/Clinical AIDS Vaccine Development program [P01 AI 49364]; Emory Center for AIDS Research [P30 DA 12121]; Yerkes National Primate Research Center [P51 RR00165]; NIH [AI 30034]; Division of Intramural Research, NIAID, NIH FX We thank Dev Chandran for initial cloning and recombinant virus construction that were used to make the clade C recombinant, MVA71. We are indebted to Jeffrey Americo for preparation of the purified ADA gp140 protein. We are grateful to the Yerkes Division of Research Resources for the consistent excellence of veterinary care and pathology support, GeoVax Inc. for the provision of good manufacturing practice-produced clinical product for JS7 and MVA62 vaccines, and the NIH AIDS Research and Reference Reagent Program for the provision of peptides. We are indebted to H. Drake-Perrow for outstanding administrative assistance. NR 42 TC 38 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4102 EP 4111 DI 10.1128/JVI.02173-08 PG 10 WC Virology SC Virology GA 431DN UT WOS:000265041600011 PM 19224993 ER PT J AU Schreiber, MJ Holmes, EC Ong, SH Soh, HSH Liu, W Tanner, L Aw, PPK Tan, HC Ng, LC Leo, YS Low, JGH Ong, A Ooi, EE Vasudevan, SG Hibberd, ML AF Schreiber, Mark J. Holmes, Edward C. Ong, Swee Hoe Soh, Harold S. H. Liu, Wei Tanner, Lukas Aw, Pauline P. K. Tan, Hwee Cheng Ng, Lee Ching Leo, Yee Sin Low, Jenny G. H. Ong, Adrian Ooi, Eng Eong Vasudevan, Subhash G. Hibberd, Martin L. TI Genomic Epidemiology of a Dengue Virus Epidemic in Urban Singapore SO JOURNAL OF VIROLOGY LA English DT Article ID DEPENDENT RNA-POLYMERASE; MOLECULAR EPIDEMIOLOGY; EVOLUTION; SEQUENCES; OUTBREAK; THAILAND; FEVER; EMERGENCE; INFECTION; REGION AB Dengue is one of the most important emerging diseases of humans, with no preventative vaccines or antiviral cures available at present. Although one-third of the world's population live at risk of infection, little is known about the pattern and dynamics of dengue virus (DENV) within outbreak situations. By exploiting genomic data from an intensively studied major outbreak, we are able to describe the molecular epidemiology of DENV at a uniquely fine-scaled temporal and spatial resolution. Two DENV serotypes (DENV-1 and DENV-3), and multiple component genotypes, spread concurrently and with similar epidemiological and evolutionary profiles during the initial outbreak phase of a major dengue epidemic that took place in Singapore during 2005. Although DENV-1 and DENV-3 differed in viremia and clinical outcome, there was no evidence for adaptive evolution before, during, or after the outbreak, indicating that ecological or immunological rather than virological factors were the key determinants of epidemic dynamics. C1 [Schreiber, Mark J.; Ong, Swee Hoe; Liu, Wei; Tanner, Lukas; Vasudevan, Subhash G.] Novartis Inst Trop Dis, Singapore 138670, Singapore. [Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ong, Swee Hoe; Aw, Pauline P. K.; Hibberd, Martin L.] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore. [Ong, Swee Hoe] Swiss Trop Inst, CH-4002 Basel, Switzerland. [Soh, Harold S. H.] ASTAR, Inst High Performance Comp, Singapore 117528, Singapore. [Tan, Hwee Cheng; Ng, Lee Ching] Natl Environm Agcy, Singapore 228231, Singapore. [Leo, Yee Sin; Low, Jenny G. H.; Ong, Adrian] Tan Tock Seng Hosp, Singapore 308433, Singapore. [Ooi, Eng Eong] DSO Natl Labs, Singapore 117510, Singapore. RP Schreiber, MJ (reprint author), Novartis Inst Trop Dis, 10 Biopolis Rd,Chromos 05-01, Singapore 138670, Singapore. EM mark.schreiber@novartis.com RI Hibberd, Martin/D-5050-2009; OI Ong, Swee Hoe/0000-0002-3629-5387; Hibberd, Martin/0000-0001-8587-1849; Holmes, Edward/0000-0001-9596-3552 FU NIH [GM080533-01]; Singapore BioMedical Research; Singapore Agency for Science Technology and Research; Singapore Tissue Network; Novartis Institute for Tropical Diseases FX We thank the staff involved in undertaking the EDEN study, together with Lai Yee Ling from the Environmental Health Institute, Fu Xiuju from the Institute for High Performance Computing, and Leng Marcel from the National University of Singapore. We thank Edison Liu and Duane Gubler for useful comments on the manuscript.; M.J.S., W.L., and S.G.V. are employed by the Novartis Institute for Tropical Diseases, which is funded by Novartis AG for the purpose of developing anti-dengue therapies. S.H.O. is a Novartis-funded Ph.D. candidate at the University of Basel. L.T. was enrolled in the Joint M.Sc. Programme in Infectious Diseases organized in conjunction with the National University of Singapore, the Novartis Institute of Tropical Diseases, the Swiss Tropical Institute, and the University of Basel.; This study was in part funded by NIH grant number GM080533-01 to E.C.H., a Singapore BioMedical Research grant to A.O., the Singapore Agency for Science Technology and Research, the Singapore Tissue Network, and the Novartis Institute for Tropical Diseases. NR 34 TC 54 Z9 56 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4163 EP 4173 DI 10.1128/JVI.02445-08 PG 11 WC Virology SC Virology GA 431DN UT WOS:000265041600017 PM 19211734 ER PT J AU Moore, ML Chi, MH Luongo, C Lukacs, NW Polosukhin, VV Huckabee, MM Newcomb, DC Buchholz, UJ Crowe, JE Goleniewska, K Williams, JV Collins, PL Peebles, RS AF Moore, Martin L. Chi, Michael H. Luongo, Cindy Lukacs, Nicholas W. Polosukhin, Vasiliy V. Huckabee, Matthew M. Newcomb, Dawn C. Buchholz, Ursula J. Crowe, James E., Jr. Goleniewska, Kasia Williams, John V. Collins, Peter L. Peebles, R. Stokes, Jr. TI A Chimeric A2 Strain of Respiratory Syncytial Virus (RSV) with the Fusion Protein of RSV Strain Line 19 Exhibits Enhanced Viral Load, Mucus, and Airway Dysfunction SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; BLOOD MONONUCLEAR-CELLS; 2 DISTINCT SITES; MESSENGER-RNA; IN-VITRO; CIRCULATION PATTERNS; G GLYCOPROTEIN; AGE 13; INFECTION; REPLICATION AB Respiratory syncytial virus (RSV) is the leading cause of respiratory failure and viral death in infants. Abundant airway mucus contributes to airway obstruction in RSV disease. Interleukin-13 (IL-13) is a mediator of pulmonary mucus secretion. It has been shown that infection of BALB/c mice with the RSV line 19 strain but not with the RSV A2 laboratory strain results in lung IL-13 and mucus expression. Here, we sequenced the RSV line 19 genome and compared it to the commonly used A2 and Long strains. There were six amino acid differences between the line 19 strain and both the A2 and Long RSV strains, five of which are in the fusion (F) protein. The Long strain, like the A2 strain, did not induce lung IL-13 and mucus expression in BALB/c mice. We hypothesized that the F protein of RSV line 19 is more mucogenic than the F proteins of A2 and Long. We generated recombinant, F-chimeric RSVs by replacing the F gene of A2 with the F gene of either line 19 or Long. Infection of BALB/c mice with RSV rA2 line 19F resulted in lower alpha interferon lung levels 24 h postinfection, higher lung viral load, higher lung IL-13 levels, greater airway mucin expression levels, and greater airway hyperresponsiveness than infection with rA2-A2F or rA2-LongF. We identified the F protein of RSV line 19 as a factor that plays a role in pulmonary mucin expression in the setting of RSV infection. C1 [Moore, Martin L.; Chi, Michael H.; Polosukhin, Vasiliy V.; Huckabee, Matthew M.; Newcomb, Dawn C.; Goleniewska, Kasia; Peebles, R. Stokes, Jr.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Crowe, James E., Jr.; Williams, John V.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. [Crowe, James E., Jr.] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. [Luongo, Cindy; Buchholz, Ursula J.; Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. [Lukacs, Nicholas W.] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. RP Moore, ML (reprint author), Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. EM martin.moore@emory.edu; stokes.peebles@vanderbilt.edu RI Crowe, James/B-5549-2009; Williams, John/F-6962-2010 OI Crowe, James/0000-0002-0049-1079; Williams, John/0000-0001-8377-5175 FU NIH [HL069949, AI054660, AI 070672, HL090664, GM15431, T32 GM07569, T32 HL069765]; Thrasher Research Fund New Researcher Award; NIAID, NIH FX We thank Frank Cook (University of Kentucky) for the pLG 338-30 plasmid. We thank Barney Graham for helpful discussions and for providing RSV A2 and Long strains. NR 61 TC 64 Z9 64 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4185 EP 4194 DI 10.1128/JVI.01853-08 PG 10 WC Virology SC Virology GA 431DN UT WOS:000265041600019 PM 19211758 ER PT J AU McNally, KL Ward, AE Priola, SA AF McNally, Kristin L. Ward, Anne E. Priola, Suzette A. TI Cells Expressing Anchorless Prion Protein Are Resistant to Scrapie Infection SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VITRO; PRP; CONVERSION; SURFACE; BSE; RETROVIRUS; MEMBRANES; MUTANT; AGENT; STATE AB The hallmark of transmissible spongiform encephalopathies (TSEs or prion diseases) is the accumulation of an abnormally folded, partially protease-resistant form (PrP-res) of the normal protease-sensitive prion protein (PrP-sen). PrP-sen is attached to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor. In vitro, the anchor and the local membrane environment are important for the conversion of PrP-sen to PrP-res. In vivo, however, the anchor is not necessary because transgenic mice expressing anchorless PrP-sen accumulate PrP-res and replicate infectivity. To clarify the role of the GPI anchor in TSE infection, cells expressing GPI-anchored PrP-sen, anchorless PrP-sen, or both forms of PrP-sen were exposed to the mouse scrapie strain 22L. Cells expressing anchored PrP-sen produced PrP-res after exposure to 22L. Surprisingly, while cells expressing anchorless PrP-sen made anchorless PrP-res in the first 96 h postinfection, no PrP-res was detected at later passes. In contrast, when cells expressing both forms of PrP-sen were exposed to 22L, both anchored and anchorless PrP-res were detected over multiple passes. Consistent with the in vitro data, scrapie-infected cells expressing anchored PrP-sen transmitted disease to mice whereas cells expressing anchorless PrP-sen alone did not. These results demonstrate that the GPI anchor on PrP-sen is important for the persistent infection of cells in vitro. Our data suggest that cells expressing anchorless PrP-sen are not directly infected with scrapie. Thus, PrP-res formation in transgenic mice expressing anchorless PrP-sen may be occurring extracellularly. C1 [McNally, Kristin L.; Ward, Anne E.; Priola, Suzette A.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM spriola@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases [1-Z01-AI000752-12] FX We thank Bruce Chesebro, Sonja Best, and Mikael Klingeborn for critical reading of the manuscript. We also thank Gary Hettrick and Anita Mora for technical assistance in the preparation of the figures. This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (project 1-Z01-AI000752-12). NR 29 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4469 EP 4475 DI 10.1128/JVI.02412-08 PG 7 WC Virology SC Virology GA 431DN UT WOS:000265041600046 PM 19225008 ER PT J AU Matsuoka, Y Swayne, DE Thomas, C Rameix-Welti, MA Naffakh, N Warnes, C Altholtz, M Donis, R Subbarao, K AF Matsuoka, Yumiko Swayne, David E. Thomas, Colleen Rameix-Welti, Marie-Anne Naffakh, Nadia Warnes, Christine Altholtz, Melanie Donis, Ruben Subbarao, Kanta TI Neuraminidase Stalk Length and Additional Glycosylation of the Hemagglutinin Influence the Virulence of Influenza H5N1 Viruses for Mice SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; IN-VITRO; OSELTAMIVIR; GROWTH; SITE; REPLICATION; SENSITIVITY; ALTER AB Following circulation of avian influenza H5 and H7 viruses in poultry, the hemagglutinin ( HA) can acquire additional glycosylation sites, and the neuraminidase (NA) stalk becomes shorter. We investigated whether these features play a role in the pathogenesis of infection in mammalian hosts. From 1996 to 2007, H5N1 viruses with a short NA stalk have become widespread in several avian species. Compared to viruses with a long-stalk NA, viruses with a short-stalk NA showed a decreased capacity to elute from red blood cells and an increased virulence in mice, but not in chickens. The presence of additional HA glycosylation sites had less of an effect on virulence than did NA stalk length. The short-stalk NA of H5N1 viruses circulating in Asia may contribute to virulence in humans. C1 [Matsuoka, Yumiko; Warnes, Christine; Altholtz, Melanie; Donis, Ruben; Subbarao, Kanta] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA USA. [Swayne, David E.; Thomas, Colleen] USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. [Rameix-Welti, Marie-Anne; Naffakh, Nadia] CNRS, URA 3015, Inst Pasteur, Unite Genet Mol Virus ARN, Paris, France. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov OI Rameix-Welti, Marie-Anne/0000-0002-5901-3856; Naffakh, Nadia/0000-0002-0424-0277 FU Oakridge Institute for Science and Education ( ORISE); Institut Pasteur FX C. W. and M. A. were supported by Oakridge Institute for Science and Education ( ORISE) fellowships. M.- A. R.- W. was supported by a fellowship from the Institut Pasteur. NR 24 TC 111 Z9 122 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY 1 PY 2009 VL 83 IS 9 BP 4704 EP 4708 DI 10.1128/JVI.01987-08 PG 5 WC Virology SC Virology GA 431DN UT WOS:000265041600070 PM 19225004 ER PT J AU Davis, BJ Haneke, KE Miner, K Kowalik, A Barrett, JC Peddada, S Baird, DD AF Davis, Barbara J. Haneke, Karen E. Miner, Kelly Kowalik, Ania Barrett, J. Carl Peddada, Shyamal Baird, Donna Day TI The Fibroid Growth Study: Determinants of Therapeutic Intervention SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PREMENOPAUSAL WOMEN; UTERINE LEIOMYOMA; AGE AB Aims: The demographics, ethnicity, symptoms, lifestyle characteristics, and treatment outcomes are analyzed in participants of a study designed to evaluate uterine leiomyoma growth and correlate symptoms and outcomes in a clinically relevant population of women (Fibroid Growth Study). Methods: Women included in the Fibroid Growth Study (FGS) completed a medical history and physical examination, underwent T1-weighted and T2-weighted magnetic resonance image (MRI) scans, provided urine and blood samples at each scheduled MRI, and responded to an initial extensive telephone-administered questionnaire followed by abbreviated monthly questionnaire updates. Summary scores were developed to quantify stress, pain, and bleeding. The Wilcoxin test was used for statistical comparisons between study participant characteristics and tumor-related characteristics. Results: Participants included 116 premenopausal women, ranging in age from 20 to 54 years; 48% were black women, 41% were white women, 10% were women of other or multiple racial backgrounds, and 1% did not self-identify. Over 90% of participants had multiple leiomyomas, and nearly a third had more than 10. Black women were younger and had more fibroids, but no differences were found in the proportions of black and white women choosing an intervention; 44% of black women and 40% of white women chose intervention during the study. Conclusions: There was no correlation between number of leiomyomas or uterine size and choosing treatment. However, women who opted for treatment were more symptomatic, with higher bleeding and pain scores, compared with the women with no intervention. Consequently, our study suggests that once women are symptomatic, black and white women choose surgery as a treatment method for the same reasons and at about the same rates. Moreover, our data suggest that bleeding and pain, not the size or multiplicity of fibroids, determine the choice for intervention. Therefore, aggressive management of pain and bleeding may be effective in reducing the need for surgical intervention. C1 [Davis, Barbara J.; Miner, Kelly; Peddada, Shyamal; Baird, Donna Day] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Haneke, Karen E.] Integrated Syst Lab, Res Triangle Pk, NC USA. [Kowalik, Ania] Univ N Carolina, Chapel Hill, NC USA. [Barrett, J. Carl] NCI, Bethesda, MD 20892 USA. RP Davis, BJ (reprint author), Millennium Pharmaceut Inc, 35 Landsdowne St, Cambridge, MA 02139 USA. EM Barbara.Davis@MPI.com RI Peddada, Shyamal/D-1278-2012; Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU NIH [M01RR00046]; NIEHS; National Center for Research on Minority Health and Health Disparities, NIH; National Uterine Fibroid Foundation FX We gratefully acknowledge Drs. Richard Semelka, Diane Armao, Xiaoyu Ding, Stephen Aylward, Bruce Lessey, Kimberly Cummings, Jane Schroeder, David Walmer, and Ray Tice and Mr. Jean-Philippe Guyon for their contributions in study design and data analysis and acknowledge the critical contributions of Ms. Martha Turvey, who was the study nurse. Dr. Ronald Herbert, Ms. Mary Wood, Ms. Paulette Daniel, Ms. Andrea Emmanuel, and Dr. Pamela Blackshear were also involved in additional study conduct, data collection, and analysis. We gratefully acknowledge the input on our study design and questionnaires of members of the National Uterine Fibroid Foundation. NR 7 TC 13 Z9 14 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2009 VL 18 IS 5 BP 725 EP 732 DI 10.1089/jwh.2008.0903 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 446DP UT WOS:000266100900017 PM 19366341 ER PT J AU Hsu, FC Kritchevsky, SB Liu, YM Kanaya, A Newman, AB Perry, SE Visser, M Pahor, M Harris, TB Nicklas, BJ AF Hsu, Fang-Chi Kritchevsky, Stephen B. Liu, Yongmei Kanaya, Alka Newman, Anne B. Perry, Sara E. Visser, Marjolein Pahor, Macro Harris, Tamara B. Nicklas, Barbara J. CA Hlth ABC Study TI Association Between Inflammatory Components and Physical Function in the Health, Aging, and Body Composition Study: A Principal Component Analysis Approach SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Inflammation; Physical function; Aging; Principal component analysis ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; OLDER-ADULTS; MUSCLE MASS; PLASMA IL-6; INTERLEUKIN-6; EXERCISE; MARKERS; WOMEN; ABC AB Background. In older adults, studies demonstrate an inverse relationship between physical function and individual inflammatory biomarkers. Given that the inflammatory response is a complex system, a combination of biomarkers may increase the strength and consistency of these associations. This study uses principal component analysis to identify inflammatory "component(s)" and evaluates associations between the identified component(s) and measures of physical function. Methods. Principal component analysis with a varimax rotation was used to identify two components from eight inflammatory biomarkers measured in 1,269 older persons. The study sample is a subset of the Health, Aging, and Body Composition study. Results. The two components explained 56% of the total variance in the data (34%, component 1 and 22%, component 2). Five markers (tumor necrosis factor-alpha [TNF-alpha], sTNFRI, sTNFRII, interleukin [IL]-6sR, IL-2sR) loaded highest on the first component (TNF-alpha related), whereas three markers (C-reactive protein [CRP], IL-6, plasminogen activator inhibitor-1) loaded highest on the second component (CRP related). After adjusting for age, sex, race, site, sampling indicator, total lean and fat mass, physical activity, smoking, and anti-inflammatory drug use, knee strength and a physical performance battery score were inversely related to the TNF-alpha-related component, but not to the CRP-related component (knee strength: (beta) over cap (TNF alpha) = -2.71, p = .002; (beta) over cap (CRP) = -0.88, p = .325; physical performance battery score: (beta) over cap (TNF alpha) = -0.05, p < .001; <(beta)over cap>(CRP) = -0.02, p = .171). Both components were positively associated with 400-m walk time, inversely associated with grip strength, and not associated with 20-m walking speed. Conclusions. At least two infl ammatory components can be identifi ed in an older population, and these components have inconsistent associations with different aspects of physical performance. C1 [Hsu, Fang-Chi] Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27101 USA. [Kritchevsky, Stephen B.; Nicklas, Barbara J.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27101 USA. [Kritchevsky, Stephen B.; Nicklas, Barbara J.] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27101 USA. [Liu, Yongmei] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA. [Kanaya, Alka] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Newman, Anne B.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. [Perry, Sara E.] Tulane Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, Inst Hlth Sci, Amsterdam, Netherlands. [Pahor, Macro] Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. [Harris, Tamara B.] Natl Inst Aging, Geriatr Epidemiol Sect, Bethesda, MD USA. RP Hsu, FC (reprint author), Wake Forest Univ, Sch Med, Dept Biostat Sci, 100 N Main St,Suite 2323, Winston Salem, NC 27101 USA. EM fhsu@wfubmc.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Intramural Research Program of the National Institutes of Health FX This research was supported by the National Institute on Aging contract Nos. N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. We thank the two reviewers for their helpful comments that improved the manuscript. NR 34 TC 47 Z9 48 U1 3 U2 11 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2009 VL 64 IS 5 BP 581 EP 589 DI 10.1093/gerona/glp005 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 431WQ UT WOS:000265095900010 PM 19228783 ER PT J AU Scuteri, A Morrell, CH Najjar, SS Muller, D Andres, R Ferrucci, L Lakatta, EG AF Scuteri, Angelo Morrell, Christopher H. Najjar, Samer S. Muller, Denis Andres, Reubin Ferrucci, Luigi Lakatta, Edward G. TI Longitudinal Paths to the Metabolic Syndrome: Can the Incidence of the Metabolic Syndrome Be Predicted? The Baltimore Longitudinal Study of Aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Metabolic syndrome; Incidence; Longitudinal studies; Abdominal obesity ID NUTRITION EXAMINATION SURVEY; INSULIN-RESISTANCE SYNDROME; 3RD NATIONAL-HEALTH; TREATMENT-PANEL-III; BODY-MASS-INDEX; BLOOD-PRESSURE; WAIST CIRCUMFERENCE; RISK; OBESITY; CHOLESTEROL AB To determine the predictors of incidence of metabolic syndrome (MetS) (Adult Treatment Panel III criteria) and to determine if longitudinal changes in specific MetS components differ by age or gender in participants who developed versus those who did not develop MetS. A total of 506 men and 461 women (baseline age 52.4 +/- 17.5 years) from the Baltimore Longitudinal Study on Aging (BLSA) were followed longitudinally (at least two study visits), and censored when they developed the MetS or reported use of antihypertensive or lipid-lowering medications. After a follow-up period of 6 years, the incidence of the MetS was 25.5% in men and 14.8% in women. As many as 66% of men and 73% of women with one or two altered MetS components at baseline did not develop the MetS. Predictors of developing MetS were higher baseline abdominal obesity or triglycerides and lower high-density lipoprotein cholesterol (area under receiver-operated curve [AUC] = 0.84 in men, 0.88 in women). Addition of the rate of changes in MetS components over time slightly improved predictive accuracy (AUC = 0.94 in men, 0.92 in women). Men were more likely than women to have the MetS without obesity, whereas women were more likely than men to have the MetS without an altered glucose metabolism. The patterns of MetS components and the longitudinal changes that lead to the MetS are different in men and women. Interestingly, components with the highest prevalence prior to MetS development, such as elevated blood pressure, are not necessarily the stronger risk factors. C1 [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, UO Geriatria, I-00189 Rome, Italy. [Morrell, Christopher H.; Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Morrell, Christopher H.] Loyola Coll, Dept Math Sci, Baltimore, MD 21210 USA. [Muller, Denis; Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Andres, Reubin] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Scuteri, A (reprint author), Ist Nazl Ricovero & Cura Anziani, UO Geriatria, I-00189 Rome, Italy. EM angeloelefante@interfree.it NR 29 TC 15 Z9 16 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2009 VL 64 IS 5 BP 590 EP 598 DI 10.1093/gerona/glp004 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 431WQ UT WOS:000265095900011 PM 19270183 ER PT J AU Ambros, PF Ambros, IM Brodeur, GM Haber, M Khan, J Nakagawara, A Schleiermacher, G Speleman, F Spitz, R London, WB Cohn, SL Pearson, ADJ Maris, JM AF Ambros, P. F. Ambros, I. M. Brodeur, G. M. Haber, M. Khan, J. Nakagawara, A. Schleiermacher, G. Speleman, F. Spitz, R. London, W. B. Cohn, S. L. Pearson, A. D. J. Maris, J. M. TI International consensus for neuroblastoma molecular diagnostics: Report from the international neuroblastoma risk grouping (INRG) Biology committee SO KLINISCHE PADIATRIE LA English DT Meeting Abstract C1 [Ambros, P. F.; Ambros, I. M.] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Brodeur, G. M.; Maris, J. M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA USA. [Brodeur, G. M.; Maris, J. M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Haber, M.] Childrens Canc Inst Australia, Sydney, NSW, Australia. [Khan, J.] NCI, Bethesda, MD 20892 USA. [Nakagawara, A.] Chiba Canc Ctr, Res Inst, Chiba, Japan. [Schleiermacher, G.] Inst Curie, Paris, France. [Speleman, F.] Ctr Med Genet, Ghent, Belgium. [Spitz, R.] Univ Cologne, D-5000 Cologne 41, Germany. [London, W. B.] Univ Florida, Childrens Oncol Grp, Stat & Data Ctr, Gainesville, FL USA. [Cohn, S. L.] Univ Chicago, Chicago, IL 60637 USA. [Pearson, A. D. J.] Inst Canc Res, Paediat Sect, Surrey, England. [Pearson, A. D. J.] Royal Marsden Hosp, Surrey, England. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0300-8630 J9 KLIN PADIATR JI Klinische Padiatr. PD MAY-JUN PY 2009 VL 221 IS 3 MA 1 BP 194 EP 194 PG 1 WC Pediatrics SC Pediatrics GA 446ZL UT WOS:000266161300017 ER PT J AU Traynor, BJ Singleton, AB AF Traynor, Bryan J. Singleton, Andrew B. TI What's the FUS! SO LANCET NEUROLOGY LA English DT Editorial Material ID AMYOTROPHIC-LATERAL-SCLEROSIS; MUTATIONS; TDP-43 C1 [Traynor, Bryan J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, Bethesda, MD 20892 USA. [Singleton, Andrew B.] NIA, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. RP Traynor, BJ (reprint author), NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Traynor, Bryan/G-5690-2010 FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000958-05] NR 9 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAY PY 2009 VL 8 IS 5 BP 418 EP 419 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 435UE UT WOS:000265368000005 PM 19375659 ER PT J AU Cuzick, J Otto, F Baron, JA Brown, PH Burn, J Greenwald, P Jankowski, J La Vecchia, C Meyskens, F Senn, HJ Thun, M AF Cuzick, Jack Otto, Florian Baron, John A. Brown, Powel H. Burn, John Greenwald, Peter Jankowski, Janusz La Vecchia, Carlo Meyskens, Frank Senn, Hans Joerg Thun, Michael TI Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement SO LANCET ONCOLOGY LA English DT Review ID LOW-DOSE ASPIRIN; LONG-TERM USE; COLORECTAL-CANCER; BREAST-CANCER; CYCLOOXYGENASE-2 INHIBITOR; COLON CARCINOGENESIS; RANDOMIZED-TRIAL; REDUCED RISK; FOLLOW-UP; LARGE-BOWEL AB Evidence clearly shows a chemopreventive effect for aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) on colorectal cancer and probably other cancer types; however, data on the risk-benefit profile for cancer prevention are insufficient and no definitive recommendations can be made. Aspirin has emerged as the most likely NSAID for use in chemoprevention because of its known cardiovascular benefit and available safety and efficacy data. Other traditional NSAIDs, particularly sulindac, and selective COX-2 inhibitors are now given to patients at high risk of colorectal cancer, although these drugs do not provide cardioprotection. More studies of aspirin and cancer prevention are needed to define the lowest effective dose, the age at which to initiate therapy, the optimum treatment duration, and the subpopulations for which the benefits of chemoprevention outweigh the risks of adverse side-effects. Although it might be possible to answer some of these questions with longer follow-up of existing clinical trials, randomised controlled trials with new study designs will be needed. Future projects should investigate the effects of aspirin treatment on multiple organ systems. Cancers of interest are colorectal, breast, prostate, lung, stomach, and oesophageal. The main side-effect of aspirin is peptic ulcers; therefore coadministration of aspirin with a proton-pump inhibitor is an attractive option and is under investigation in the AspECT trial. C1 [Cuzick, Jack] Queen Mary Univ London, Canc Res UK Ctr Epidemiol Math & Stat, Barts & London Sch Med & Dent, Wolfson Inst Prevent Med, London EC1M 6BQ, England. [Otto, Florian; Senn, Hans Joerg] Turnor Ctr ZeTuP, St Gallen, Switzerland. [Otto, Florian; Senn, Hans Joerg] Univ Med Ctr, Dept Hematol & Oncol, Freiburg, Germany. [Baron, John A.] Dartmouth Med Sch, Hanover, NH USA. [Brown, Powel H.] Baylor Coll Med, Houston, TX 77030 USA. [Burn, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Greenwald, Peter] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Jankowski, Janusz] Univ Oxford, Oxford, England. [Jankowski, Janusz] Queen Mary Univ London, Inst Cellular & Mol Sci, London E1 4NS, England. [La Vecchia, Carlo] Mario Negri Inst Pharmacol Res, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Milan, Italy. [Meyskens, Frank] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA USA. [Thun, Michael] Amer Canc Soc, Atlanta, GA 30329 USA. RP Cuzick, J (reprint author), Queen Mary Univ London, Canc Res UK Ctr Epidemiol Math & Stat, Barts & London Sch Med & Dent, Wolfson Inst Prevent Med, Charterhouse Sq, London EC1M 6BQ, England. EM j.cuzick@qmul.ac.uk RI Jankowski, Janusz/H-2706-2012; OI Jankowski, Janusz/0000-0003-2130-9181; La Vecchia, Carlo/0000-0003-1441-897X FU Medical Research Council [G0100496] NR 66 TC 340 Z9 349 U1 10 U2 70 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAY PY 2009 VL 10 IS 5 BP 501 EP 507 PG 7 WC Oncology SC Oncology GA 443KH UT WOS:000265908100024 PM 19410194 ER PT J AU Mazzola, C Medalie, J Scherma, M Panlilio, LV Solinas, M Tanda, G Drago, F Cadet, JL Goldberg, SR Yasar, S AF Mazzola, Carmen Medalie, Julie Scherma, Maria Panlilio, Leigh V. Solinas, Marcello Tanda, Gianluigi Drago, Filippo Cadet, Jean Lud Goldberg, Steven R. Yasar, Sevil TI Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors SO LEARNING & MEMORY LA English DT Article ID CANNABINOID ANANDAMIDE; ENDOCANNABINOID SYSTEM; ALZHEIMERS-DISEASE; INFLAMMATORY PAIN; ANXIETY; MICE; URB597; OLEOYLETHANOLAMIDE; EICOSANOIDS; ANALGESIA AB Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB(1)-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain. Using a passive-avoidance task in rats, we found that memory acquisition was enhanced by the FAAH inhibitor URB597 or by the PPAR-alpha agonist WY14643, and these enhancements were blocked by the PPAR-alpha antagonist MK886. These findings demonstrate novel mechanisms for memory enhancement by activation of PPAR-alpha, either directly by administering a PPAR-alpha agonist or indirectly by administering a FAAH inhibitor. C1 [Yasar, Sevil] NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. [Mazzola, Carmen; Drago, Filippo] Univ Catania, Sch Med, Dept Expt & Clin Pharmacol, I-86022 Catania, Italy. [Solinas, Marcello] Univ Poitiers, CNRS 6187, Dept Lab Biol & Physiol Cellulaires, F-86022 Poitiers, France. [Tanda, Gianluigi] NIDA, Psychol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. [Yasar, Sevil] Johns Hopkins Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. RP Yasar, S (reprint author), NIDA, Mol Neuropsychiat Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. EM syasar@jhmi.edu RI Tanda, Gianluigi/B-3318-2009; Solinas, Marcello/M-3500-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; Solinas, Marcello/0000-0002-0664-5964 FU NIH; National Institute on Drug Abuse FX This research was supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. We thank Zuzana Justinova for help with preparing the figures and comments on the manuscript. NR 42 TC 65 Z9 66 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD MAY PY 2009 VL 16 IS 5 BP 332 EP 337 DI 10.1101/lm.1145209 PG 6 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 439QM UT WOS:000265642100008 PM 19403796 ER PT J AU Silverman, L Verma, A Odchimar-Reissig, R LeBlane, A Najfeld, V Gabrilove, J Isola, L Espinoza-Delgado, I Zwiebel, J AF Silverman, L. Verma, A. Odchimar-Reissig, R. LeBlane, A. Najfeld, V. Gabrilove, J. Isola, L. Espinoza-Delgado, I. Zwiebel, J. TI Phase I trial of the combination of the epigenetic modulators vorinostat and azacitidine (azaC) in patients with the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). An update from the NY Cancer Consortium SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 10th International Symposium on Myelodysplastic Syndromes CY MAY 06-09, 2009 CL Patras, GREECE SP Celgene, Novartis, Eisai, MSD, GSK, MSD, Oncol, Alexion, MDS Fdn C1 [Silverman, L.; Odchimar-Reissig, R.; LeBlane, A.; Najfeld, V.; Gabrilove, J.; Isola, L.] Mt Sinai Sch Med, New York, NY USA. [Verma, A.] Albert Einstein Coll Med, Bronx, NY USA. [Espinoza-Delgado, I.; Zwiebel, J.] NCI, NIH, Bethesda, MD 20892 USA. EM lewis.silverman@mssm.edu NR 0 TC 0 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2009 VL 33 BP S135 EP S136 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 455KX UT WOS:000266759600208 ER PT J AU Young, NS AF Young, N. S. TI Telomere biology and the pathogenesis of clonal evolution from bone marrow failure SO LEUKEMIA RESEARCH LA English DT Meeting Abstract CT 10th International Symposium on Myelodysplastic Syndromes CY MAY 06-09, 2009 CL Patras, GREECE SP Celgene, Novartis, Eisai, MSD, GSK, MSD, Oncol, Alexion, MDS Fdn C1 [Young, N. S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2009 VL 33 BP S2 EP S2 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 455KX UT WOS:000266759600004 ER PT J AU Lin, JP O'Donnell, CJ Fox, CS Cupples, LA AF Lin, Jing-Ping O'Donnell, Christopher J. Fox, Caroline S. Cupples, L. Adrienne TI Heritability of serum gamma-glutamyltransferase level: genetic analysis from the Framingham Offspring Study SO LIVER INTERNATIONAL LA English DT Letter ID POPULATION C1 [Lin, Jing-Ping] NHLBI, Off Biostat, Div Prevent & Populat Sci, NIH, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Lin, JP (reprint author), NHLBI, Off Biostat, Div Prevent & Populat Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [N01 HC025195, N01-HC-25195, N01HC25195] NR 8 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD MAY PY 2009 VL 29 IS 5 BP 777 EP 777 DI 10.1111/j.1478-3231.2008.01965.x PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430UI UT WOS:000265014300028 PM 19192172 ER PT J AU Xiao, XD Ho, M Zhu, ZY Pastan, I Dimitrov, DS AF Xiao, Xiaodong Ho, Mitchell Zhu, Zhonyu Pastan, Ira Dimitrov, Dimiter S. TI Identification and characterization of fully human anti-CD22 monoclonal antibodies SO MABS LA English DT Article DE human antibody; CD22; phage display; cancer; hematological ID B-CELL MALIGNANCIES; RECOMBINANT IMMUNOTOXIN; CD22; LEUKEMIA; INCREASE; BL22 AB CD22 is a member of the B cell receptor family and is implicated in B cell function and development. It is expressed on multiple forms of B cell lymphoma and is an attractive cancer therapeutic target. We report here the identification of two fully human anti-CD22 antibodies using phage display methodology. Both antibodies exhibit specific binding to cell surface-associated CD22 in multiple B cell lines. Through ELISA using mammalian cell-expressed sub-domains of CD22 as binding antigen, we mapped the binding epitopes of the newly identified CD22 antibodies to be within the Ig-like domains 5 to 7 of CD22. Their epitopes do not overlap with those of several therapeutic antibodies currently in preclinical or clinical development. These antibodies have potential as cancer therapeutic candidates and research reagents. C1 [Xiao, Xiaodong] NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21702 USA. [Zhu, Zhonyu] NCI, BRP, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA. [Ho, Mitchell; Pastan, Ira] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Xiao, XD (reprint author), NCI, Prot Interact Grp, CCRNP, NIH, Bldg 469,Rm 139, Frederick, MD 21702 USA. EM xiaox@ncifcrf.gov RI Ho, Mitchell/F-5059-2015 FU NIH, National Cancer Institute, Center for Cancer Research [N01-CO-12400] FX This project was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400. NR 20 TC 3 Z9 3 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS JI mAbs PD MAY-JUN PY 2009 VL 1 IS 3 BP 297 EP 303 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 521CU UT WOS:000271898000012 PM 20065646 ER PT J AU Suzuki, S Sreenath, T Haruyama, N Honeycutt, C Terse, A Cho, A Kohler, T Muller, R Goldberg, M Kulkarni, AB AF Suzuki, Shigeki Sreenath, Taduru Haruyama, Naoto Honeycutt, Cherlita Terse, Anita Cho, Andrew Kohler, Thomas Mueller, Ralph Goldberg, Michel Kulkarni, Ashok B. TI Dentin sialoprotein and dentin phosphoprotein have distinct roles in dentin mineralization SO MATRIX BIOLOGY LA English DT Article DE Dentin sialophosphoprotein; Biomineralization; Dentin volume; Dentin mineral density; Chondroitin sulfate proteoglycan ID RAT-INCISOR DENTIN; SIALOPHOSPHOPROTEIN GENE; SEQUENCE DETERMINATION; EXPRESSION PATTERNS; MATRIX PROTEINS; MOUSE TEETH; DSPP GENE; IN-VIVO; BONE; PROTEOGLYCANS AB Dentin sialophosphoprotein (DSPP), a major non-collagenous matrix protein of odontoblasts, is proteolytically cleaved into dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Our previous studies revealed that DSPP null mice display a phenotype similar to human autosomal dominant dentinogenesis imperfecta. in which teeth have widened predentin and irregular dentin mineralization resulting in sporadic unmineralized areas in dentin and frequent pulp exposure. Earlier in vitro studies suggested that DPP, but not DSP, plays a significant role in initiation and maturation of dentin mineralization. However, the precise in vivo roles of DSP and DPP are far from clear. Here we report the generation of DPPcKO mice, in which only DSP is expressed in a DSPP null background, resulting in a conditional DPP knockout. DPPcKO teeth show a partial rescue of the DSPP null phenotype with the restored predentin width, an absence of irregular unmineralized areas in dentin, and less frequent pulp exposure. Micro-computed tomography (micro-CT) analysis of DPPcKO molars further confirmed this partial rescue with a significant recovery in the dentin volume, but not in the dentin mineral density. These results indicate distinct roles of DSP and DPP in dentin mineralization, with DSP regulating initiation of dentin mineralization, and DPP being involved in the maturation of mineralized dentin. Published by Elsevier B.V. C1 [Suzuki, Shigeki; Sreenath, Taduru; Haruyama, Naoto; Honeycutt, Cherlita; Terse, Anita; Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol,Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Cho, Andrew] Natl Inst Dent & Craniofacial Res, Gene Targeting Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kohler, Thomas; Mueller, Ralph] Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland. [Goldberg, Michel] Univ Paris 05, Fac Chirurg Dentaire, Lab Reparat & Remodelage Tissues Orofaciaux EA 24, Montrouge, France. RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol,Dept Hlth & Human Serv, NIH, 30 Convent Dr,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Muller, Ralph/A-1198-2008; Haruyama, Naoto/D-1993-2011 OI Muller, Ralph/0000-0002-5811-7725; Haruyama, Naoto/0000-0001-6225-5816 FU Division of the Intramural Research, National Institute of Dental and Craniofacial Research, NIH FX We would like to thank Drs. Larry Fisher and Dianalee A. McKnight for helpful discussion and critical comments on the manuscript, and Harry Grant and Shelagh Powers for editorial assistance. These studies were supported by the Division of the Intramural Research, National Institute of Dental and Craniofacial Research, NIH. NR 50 TC 96 Z9 100 U1 3 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD MAY PY 2009 VL 28 IS 4 BP 221 EP 229 DI 10.1016/j.matbio.2009.03.006 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 467ZV UT WOS:000267783700006 PM 19348940 ER PT J AU Lakatta, EG Wang, MY Najjar, SS AF Lakatta, Edward G. Wang, Mingyi Najjar, Samer S. TI Arterial Aging and Subclinical Arterial Disease are Fundamentally Intertwined at Macroscopic and Molecular Levels SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Arterial aging; Angiotensin II; Intimal-medial thickening; Arteriosclerosis; Hypertension ID ISOLATED SYSTOLIC HYPERTENSION; SMOOTH-MUSCLE CELLS; STAGE RENAL-FAILURE; PULSE-WAVE VELOCITY; ENDOTHELIAL DYSFUNCTION; ANGIOTENSIN-II; MAJOR SHAREHOLDERS; AORTIC STIFFNESS; BLOOD-PRESSURE; INDEPENDENT PREDICTOR AB The structure and function of arteries change throughout a lifetime. Age is the dominant risk factor for hypertension, coronary heart disease, congestive heart failure, and stroke. The cellular/molecular proinflammatory alterations that underlie arterial aging are novel putative candidates to be targeted by interventions aimed at attenuating arterial aging as a major risk factor for cardiovascular diseases. This review provides a landscape of central arterial aging and age-disease interactions, integrating perspectives that range from humans to molecules, with the goal that future therapies for cardiovascular diseases, such as hypertension, also will target the prevention or amelioration of unsuccessful arterial aging. C1 [Lakatta, Edward G.; Wang, Mingyi; Najjar, Samer S.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov FU National Institute on Aging; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 75 TC 67 Z9 71 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2009 VL 93 IS 3 BP 583 EP + DI 10.1016/j.mcna.2009.02.008 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 455SB UT WOS:000266784000006 PM 19427493 ER PT J AU Han, PKJ Klein, WMP Lehman, TC Massett, H Lee, SC Freedman, AN AF Han, Paul K. J. Klein, William M. P. Lehman, Thomas C. Massett, Holly Lee, Simon C. Freedman, Andrew N. TI Laypersons' Responses to the Communication of Uncertainty Regarding Cancer Risk Estimates SO MEDICAL DECISION MAKING LA English DT Article DE uncertainty; risk; ambiguity; cancer; risk prediction models ID SHARED DECISION-MAKING; CORONARY-HEART-DISEASE; BREAST-CANCER; PERCEIVED AMBIGUITY; PREVENTION RECOMMENDATIONS; SCREENING MAMMOGRAPHY; CARDIOVASCULAR RISK; INFORMED-CONSENT; SAVAGE AXIOMS; INFORMATION AB Objective. To explore laypersons' responses to the communication of uncertainty associated with individualized cancer risk estimates and to identify reasons for individual differences in these responses. Design. A qualitative study was conducted using focus groups. Participants were informed about a new colorectal cancer risk prediction model, and presented with hypothetical individualized risk estimates using presentation formats varying in expressed uncertainty (range v. point estimate). Semistructured interviews explored participants' responses to this information. Participants and Setting. Eight focus groups were conducted with 48 adults aged 50 to 74 residing in 2 major US metropolitan areas, Chicago, IL and Washington, DC. Purposive sampling was used to recruit participants with a high school or greater education, some familiarity with information technology, and no personal or immediate family history of cancer. Results. Participants identified several sources of uncertainty regarding cancer risk estimates, including missing data, limitations in accuracy and source credibility, and conflicting information. In comparing presentation formats, most participants reported greater worry and perceived risk with the range than with the point estimate, consistent with the phenomenon of "ambiguity aversion.'' However, others reported the opposite effect or else indifference between formats. Reasons suggested by participants' responses included individual differences in optimism and motivations to reduce feelings of vulnerability and personal lack of control. Perceptions of source credibility and risk mutability emerged as potential mediating factors. Conclusions. Laypersons' responses to the communication of uncertainty regarding cancer risk estimates differ, and include both heightened and diminished risk perceptions. These differences may be attributable to personality, cognitive, and motivational factors. C1 [Han, Paul K. J.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Massett, Holly] NCI, Operat Res Off, Bethesda, MD 20892 USA. [Klein, William M. P.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Lehman, Thomas C.] Acad Educ Dev, Ctr Social Mkt & Behav Change, Washington, DC USA. RP Han, PKJ (reprint author), NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, 6130 Executive Blvd,EPN 4091,MSC 7344, Bethesda, MD 20892 USA. EM hanp@mail.nih.gov RI Lee, Simon/B-2443-2008; OI Han, Paul/0000-0003-0165-1940; Lee, Simon J. Craddock/0000-0001-6345-1237 FU National Cancer Institute FX Received 6 February 2008 from the Division of Cancer Control and Population Sciences (PKJH, SCL, ANF) and Operations Research Office (HM), National Cancer Institute, Bethesda, Maryland; Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania (WMPK); and Center for Social Marketing and Behavior Change, Academy for Educational Development, Washington, DC (TL). Financial support for this study was provided by intramural research funds from the National Cancer Institute. The following authors are employed by the sponsor: Paul K. J. Han, Holly Massett, Simon C. Lee, and Andrew N. Freedman. Revision accepted for publication 25 August 2008. NR 90 TC 28 Z9 28 U1 2 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY PY 2009 VL 29 IS 3 BP 391 EP 403 DI 10.1177/0272989X08327396 PG 13 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 455MM UT WOS:000266764700016 PM 19470720 ER PT J AU Vamecq, J Feutelais, Y Maurois, P Sghaier, M Dichi, E German-Fattal, M Herrenknecht, C Gressens, P Cecchelli, R Dehouck, L Stables, JP Pages, N Legendre, B Bac, P AF Vamecq, Joseph Feutelais, Yves Maurois, Pierre Sghaier, Mehrez Dichi, Emma German-Fattal, Michele Herrenknecht, Christine Gressens, Pierre Cecchelli, Romeo Dehouck, Lucie Stables, James P. Pages, Nicole Legendre, Bernard Bac, Pierre TI Engineering a GABA endowed with pharmacological CNS activity when given by an extracerebral route SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article DE Gamma-aminobutyric acid (GABA); Tetragonal phase; Monoclinic phase; gauche conformer; trans conformer; Sublimation under vacuum ID BLOOD-BRAIN-BARRIER; TRANSPORT; MODEL AB Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter physiologically active in the central nervous system (CNS), being synthesised and delivered by GABAergic neurons. It is, however, pharmacologically devoid of CNS activity when presented externally to brain because of limited blood-brain barrier diffusion and intensive breakdown by astrocyte GABA transaminase. We show herein that extracerebral administration may be, however, pharmacologically effective in controlling experimental convulsive attacks when GABA is submitted to sublimation under vacuum just before use. Though initially enigmatic because nuclear magnetic resonance (NMR) and infrared (IR) analyses identified the sublimation-derived compound to be the reference zwitterionic GABA, this observation was understood by showing that the reference and sublimated GABAs were monoclinic and tetragonal phases of GABA solid, respectively. C1 [Vamecq, Joseph] Inserm Univ 045131, IMPRT IFR114, EA 1046, F-59045 Lille, France. [Feutelais, Yves; Maurois, Pierre; Sghaier, Mehrez; Dichi, Emma; German-Fattal, Michele; Herrenknecht, Christine; Legendre, Bernard; Bac, Pierre] Univ Paris Sud, CNRS, UMR & Chim Analyt 8078, EA 401, F-92296 Chatenay Malabry, France. [Maurois, Pierre; German-Fattal, Michele; Bac, Pierre] Ctr Chirurg Marie Lannelongue, CNRS, UMR 8162, F-92350 Le Plessis Robinson, France. [Gressens, Pierre] Hop Robert Debre, INSERM, U676, F-75019 Paris, France. [Gressens, Pierre] Univ Paris 07, IFR02, Fac Med Denis Diderot, F-75018 Paris, France. [Gressens, Pierre] Univ Paris 07, IFR25, F-75018 Paris, France. [Cecchelli, Romeo; Dehouck, Lucie] Artois Univ, Fac Jean Perrin, IMPRT IFR114, EA 2465,Lab Blood Brain Barrier, F-62037 Lens, France. [Stables, James P.] NINDS, Preclin Pharmacol Sect, Epilepsy Branch, DCDND,NIH, Bethesda, MD 20892 USA. [Pages, Nicole] Univ Strasbourg 1, F-67401 Illkirch Graffenstaden, France. RP Vamecq, J (reprint author), Inserm Univ 045131, IMPRT IFR114, EA 1046, F-59045 Lille, France. EM joseph.vamecq@inserm.fr NR 9 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER BIRKHAUSER PI NEW YORK PA 233 SPRING STREET, 6TH FLOOR, NEW YORK, NY 10013 USA SN 1054-2523 EI 1554-8120 J9 MED CHEM RES JI Med. Chem. Res. PD MAY PY 2009 VL 18 IS 4 BP 255 EP 267 DI 10.1007/s00044-008-9124-1 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 438QB UT WOS:000265569300002 ER PT J AU Lupsa, BC Chong, AY Cochran, EK Soos, MA Semple, RK Gorden, P AF Lupsa, Beatrice C. Chong, Angeline Y. Cochran, Elaine. K. Soos, Maria A. Semple, Robert K. Gorden, Phillip TI Autoimmune Forms of Hypoglycemia SO MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; B INSULIN-RESISTANCE; ANTIINSULIN RECEPTOR ANTIBODIES; SYNDROME HIRATA DISEASE; RECURRENT HYPOGLYCEMIA; RECEIVING PENICILLAMINE; FASTING HYPOGLYCEMIA; MULTIPLE-MYELOMA; BINDING ANTIBODY; HODGKINS-DISEASE AB Autoimmune syndromes are a rare cause of hypoglycemia charactcrized by elevated levels of insulin in the presence of either anti-insulin antibodies (insulin autoimmune syndrome) or anti-insulin receptor antibodies (type B insulin resistance). Insulin autoimmune syndrome is the third leading cause of hypoglycemia in Japan, but has rarely been described in the non-Asian population. In the Current study, we report the clinical and biochemical characteristics and clinical course of 2 white patients with insulin autoimmune syndrome, and present a literature review of non-Asian patients reported with insulin autoimmune syndrome. Also, we describe the clinical and biochemical characteristics of patients reported in the literature with type B insulin resistance who manifested hypoglycemia. We compare the clinical and laboratory features of insulin autoimmune syndrome and type B insulin resistance with each other and with other forms of hyperinsulinemic hypoglycemia. Autoimmune forms of hypoglycemia are uncommon. However, they should be considered in any patient with hypoglycemia in the setting of unsuppressed insulin levels associated with anti-insulin or anti-insulin receptor antibodies. Making the correct diagnosis may spare a hypoglycemic patient from an unnecessary pancreatic surgical procedure. (Medicine 2009;88: 141-153) C1 [Lupsa, Beatrice C.; Chong, Angeline Y.; Cochran, Elaine. K.; Gorden, Phillip] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. [Soos, Maria A.; Semple, Robert K.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England. RP Gorden, P (reprint author), 10 Ctr Dr,MSC 1612,Room CRC 6-5940, Bethesda, MD 20892 USA. EM phillipg@intra.niddk.nih.gov OI Semple, Robert/0000-0001-6539-3069 FU National Institutes of Health, Bethesda, Maryland; Wellcome Trust FX This work was supported by intramural research funding of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, Bethesda, Maryland, and by the Wellcome Trust. NR 93 TC 55 Z9 62 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2009 VL 88 IS 3 BP 141 EP 153 DI 10.1097/MD.0b013e3181a5b42e PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 446UT UT WOS:000266147600002 PM 19440117 ER PT J AU Fitch, KV Guggina, LM Keough, HM Looby, SED Hadigan, C Anderson, EJ Hubbard, J Liebau, JG Johnsen, S Wei, J Makimura, H Stanley, TL Lo, J Grinspoon, SK AF Fitch, Kathleen V. Guggina, LaUren M. Keough, Hester M. Looby, Sara E. Dolan Hadigan, Colleen Anderson, Ellen J. Hubbard, Jane Liebau, James G. Johnsen, Stine Wei, Jeffery Makimura, Hideo Stanley, Takara L. Lo, Janet Grinspoon, Steven K. TI Decreased respiratory quotient in relation to resting energy expenditure in HIV-infected and noninfected subjects SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HIGH-FAT DIET; LIPODYSTROPHY SYNDROME; INSULIN SENSITIVITY; METABOLIC SYNDROME; CONTROLLED-TRIAL; BONE-DENSITY; WEIGHT-LOSS; WOMEN AB The purpose of this study was to evaluate the relationship of respiratory quotient (RQ), a surrogate marker of substrate oxidation, as well as body composition and dietary intake to resting energy expenditure (REE) among HIV-infected patients in the current era of highly active antiretroviral therapy and among non-HIV-infected control subjects. Resting energy expenditure is increased in HIV-infected patients; but little is known regarding the potential contribution of altered substrate metabolism, body composition, and dietary intake to increased energy expenditure in this Population. Respiratory quotient, REE, body composition, and dietary intake parameters were assessed in 283 HIV-infected patients and 146 community-derived HIV-negative controls who were evaluated for metabolic Studies between 1998 and 2005. Respiratory quotient was lower (0.83 +/- 0.00 vs 0.85 +/- 0.01, P = .005), whereas REE adjusted for fat-free mass (FFM) was higher (31.8 +/- 0.3 vs 29.8 +/- 0.3 kcal/[d kg], P <= .0001), in HIV-infected compared with control subjects. In multivariate modeling among HIV-infected patients, including age, sex, and parameters of immune function, FFM (beta = 24.811334, P < .0001), visceral adiposity (beta = .7182746, P = .008), and total body fat (beta = 8.0506839, P = .041) were positively associated with REE. whereas RQ was negatively associated with REE (beta = -528.4808, P = .024). Overall r(2) was equal to 0.705 and P was less than .0001 for the model. In control subjects, by contrast, only visceral adiposity (beta = 1.0612073, P = .004), total body fat (beta = 15.805547, P = .010), and FFM (beta = 22.613005, P < .0001) were significant predictors of REE and there was no relationship with RQ. Overall r(2) was equal to 0.825 and P was less than .0001 for the model. These data suggest that alterations in substrate metabolism may contribute to increased REE in HIV-infected patients compared with control subjects. (C) 2009 Elsevier Inc. All rights reserved. C1 [Fitch, Kathleen V.; Guggina, LaUren M.; Keough, Hester M.; Looby, Sara E. Dolan; Hadigan, Colleen; Liebau, James G.; Johnsen, Stine; Wei, Jeffery; Makimura, Hideo; Stanley, Takara L.; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Anderson, Ellen J.; Hubbard, Jane] Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. [Hadigan, Colleen] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health (NIH) [DKRO1-49302, NIH DK-02844, NIH T32HD-052691, NIH K24 DK064545, NIH MO1-RR01066]; Mary Fisher Clinical AIDS Research and Education Fund FX This work was supported by National Institutes of Health (NIH) DKRO1-49302, NIH DK-02844, NIH T32HD-052691, NIH K24 DK064545, NIH MO1-RR01066, and the Mary Fisher Clinical AIDS Research and Education Fund. We wish to thank the nutrition and nursing staff of the MGH and MIT General Clinical Research Center for their dedicated patient care. NR 40 TC 7 Z9 7 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 2009 VL 58 IS 5 BP 608 EP 615 DI 10.1016/j.metabol.2008.12.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 439YL UT WOS:000265663700005 PM 19375582 ER PT J AU Guo, R Xu, DY Wang, WD AF Guo, Rong Xu, Dongyi Wang, Weidong TI Identification and analysis of new proteins involved in the DNA damage response network of Fanconi anemia and Bloom syndrome SO METHODS LA English DT Review DE BLM; Fancom anemia; Topoisomerase 3a; RMI ID COMPLEX; COMPONENTS; CHROMATIN AB The use of co-immunoprecipitation (co-IP) to purify multi-protein complexes has contributed greatly to our understanding of the DNA damage response network associated with Fanconi anemia (FA), Bloom syndrome (BS) and breast cancer. Four new FA genes and two new protein partners for the Bloom syndrome gene product have been identified by co-IP. Here, we discuss our experience in using co-IP and other techniques to isolate and characterize new FA and BS-related proteins. Published by Elsevier Inc. C1 [Guo, Rong; Xu, Dongyi; Wang, Weidong] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wang, WD (reprint author), NIA, Genet Lab, NIH, Biomed Res Ctr, Room 10B113,251 Bayview Blvd, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov OI Xu, Dongyi/0000-0001-5711-2618 FU Intramural NIH HHS [Z01 AG000657-08]; NIA NIH HHS [Z01 AG000657-08, Z01 AG000657] NR 19 TC 12 Z9 12 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2009 VL 48 IS 1 BP 72 EP 79 DI 10.1016/j.ymeth.2009.02.011 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 459WQ UT WOS:000267143800011 PM 19245838 ER PT J AU Ozbudak, IH Shilo, K Tavora, F Rassaei, N Chu, WS Fukuoka, J Jen, J Travis, WD Franks, TJ AF Ozbudak, Irem H. Shilo, Konstantin Tavora, Fabio Rassaei, Negar Chu, Wei-Sing Fukuoka, Junya Jen, Jin Travis, William D. Franks, Teri J. TI Glucose transporter-1 in pulmonary neuroendocrine carcinomas: expression and survival analysis SO MODERN PATHOLOGY LA English DT Article DE GLUT-1; neuroendocrine carcinoma; carcinoid; survival; lung ID CELL LUNG-CANCER; GLUCOSE-TRANSPORTER EXPRESSION; HUMAN BREAST-CARCINOMA; GLUT1 EXPRESSION; FDG UPTAKE; HYPOXIA; HIF-1-ALPHA; STAGE AB Glucose transporter-1 (GLUT-1) mediates the transport of glucose across the cellular membrane. Its elevated levels and/or activation have been shown to be associated with malignancy. The aim of this study was to investigate GLUT-1 expression in pulmonary neuroendocrine carcinomas. Tissue microarray-based samples of 178 neuroendocrine carcinomas, including 48 typical carcinoids, 31 atypical carcinoids, 27 large cell neuroendocrine carcinomas and 72 small cell carcinomas from different patients, were studied immunohistochemically for GLUT-1 expression. Forty-seven percent (75/161) of pulmonary neuroendocrine carcinomas were immunoreactive with GLUT-1. GLUT-1 was observed in 7% (3/46) of typical carcinoid, 21% (6/29) of atypical carcinoid, 74% (17/23) of large cell neuroendocrine carcinoma and 78% (49/63) of small cell carcinoma. GLUT-1 expression correlated with increasing patient age (P = 0.01) and with neuroendocrine differentiation/tumor type (P < 0.001), but not with gender, tumor size or stage. GLUT-1 expression was seen in a characteristic membranous pattern of staining along the luminal borders or adjacent to necrotic areas. GLUT-1 expression was associated with an increased risk of death for neuroendocrine carcinomas as a group (risk ratio = 2.519; 95% confidence interval = 1.519-4.178; P < 0.001) and carcinoids (risk ratio = 4.262; 95% confidence interval = 1.472-12.343; P = 0.01). In conclusion, GLUT-1 is expressed in approximately half of the pulmonary neuroendocrine carcinomas and shows a strong correlation with neuroendocrine differentiation/grade, but not with other clinicopathologic variables. Further studies appear plausible to elucidate the prognostic significance of GLUT-1 expression in pulmonary carcinoids. Modern Pathology (2009) 22, 633-638; doi: 10.1038/modpathol.2009.6; published online 20 February 2009 C1 [Shilo, Konstantin; Tavora, Fabio; Rassaei, Negar; Franks, Teri J.] Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. [Ozbudak, Irem H.] Akdeniz Univ, Sch Med, Dept Pathol, TR-07058 Antalya, Turkey. [Chu, Wei-Sing] Armed Forces Inst Pathol, Dept Sci Labs, Washington, DC 20306 USA. [Fukuoka, Junya] Toyama Univ Hosp, Pathol Lab, Toyama, Japan. [Jen, Jin] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Travis, William D.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Shilo, K (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 16th St NW, Washington, DC 20306 USA. EM shilok@afip.osd.mil RI Shilo, Konstantin/E-4084-2011; Tavora, Fabio/A-7561-2009; Ozbudak, Irem /C-4815-2016; OI S, K/0000-0002-6702-3130 FU Intramural NIH HHS [Z01 CP010164-07]; NCI NIH HHS [R01 CA084354, R01 CA080127]; NIA NIH HHS [P50 AG016574] NR 25 TC 18 Z9 20 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 2009 VL 22 IS 5 BP 633 EP 638 DI 10.1038/modpathol.2009.6 PG 6 WC Pathology SC Pathology GA 439PT UT WOS:000265640200004 PM 19234439 ER PT J AU Yuan, ZM Gong, SF Luo, JY Zheng, ZH Song, B Ma, SS Guo, JL Hu, C Thiel, G Vinson, C Hu, CD Wang, YZ Li, MT AF Yuan, Zhongmin Gong, Shoufang Luo, Jingyan Zheng, Zhihao Song, Bin Ma, Shanshan Guo, Jiaoli Hu, Ce Thiel, Gerald Vinson, Charles Hu, Chang-Deng Wang, Yizheng Li, Mingtao TI Opposing Roles for ATF2 and c-Fos in c-Jun-Mediated Neuronal Apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CEREBELLAR GRANULE NEURONS; N-TERMINAL KINASE; ACTIVATED PROTEIN-KINASES; PROGRAMMED CELL-DEATH; GENE-EXPRESSION; TRANSCRIPTION FACTOR; POTASSIUM DEPRIVATION; FAS LIGAND; SYMPATHETIC NEURONS; RESPONSE ELEMENT AB The activator protein 1 (AP-1) transcription factor c-Jun is crucial for neuronal apoptosis. However, c-Jun dimerization partners and the regulation of these proteins in neuronal apoptosis remain unknown. Here we report that c-Jun-mediated neuronal apoptosis requires the concomitant activation of activating transcription factor-2 (ATF2) and downregulation of c-Fos. Furthermore, we have observed that c-Jun predominantly heterodimerizes with ATF2 and that the c-Jun/ATF2 complex promotes apoptosis by triggering ATF activity. Inhibition of c-Jun/ATF2 heterodimerization using dominant negative mutants, small hairpin RNAs, or decoy oligonucleotides was able to rescue neurons from apoptosis, whereas constitutively active ATF2 and c-Jun mutants were found to synergistically stimulate apoptosis. Bimolecular fluorescence complementation analysis confirmed that, in living neurons, c-Fos downregulation facilitates c-Jun/ATF2 heterodimerization. A chromatin immunoprecipitation assay also revealed that c-Fos expression prevents the binding of c-Jun/ATF2 heterodimers to conserved ATF sites. Moreover, the presence of c-Fos is able to suppress the expression of c-Jun/ATF2-mediated target genes and, therefore, apoptosis. Taken together, our findings provide evidence that potassium deprivation-induced neuronal apoptosis is mediated by concurrent upregulation of c-Jun/ATF2 heterodimerization and downregulation of c-Fos expression. This paradigm demonstrates opposing roles for ATF2 and c-Fos in c-Jun-mediated neuronal apoptosis. C1 [Yuan, Zhongmin; Gong, Shoufang; Luo, Jingyan; Zheng, Zhihao; Song, Bin; Ma, Shanshan; Guo, Jiaoli; Hu, Ce; Li, Mingtao] Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, Guangzhou 510080, Guangdong, Peoples R China. [Yuan, Zhongmin; Gong, Shoufang; Luo, Jingyan; Zheng, Zhihao; Song, Bin; Ma, Shanshan; Guo, Jiaoli; Hu, Ce; Li, Mingtao] Sun Yat Sen Univ, Zhongshan Sch Med, Prote Ctr, Guangzhou 510080, Guangdong, Peoples R China. [Thiel, Gerald] Univ Saarland, Dept Med Biochem & Mol Biol, Med Ctr, D-66421 Homburg, Germany. [Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Hu, Chang-Deng] Purdue Univ, Dept Med Chem & Mol Pharmacol, Purdue Canc Ctr, W Lafayette, IN 47907 USA. [Wang, Yizheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. RP Li, MT (reprint author), Sun Yat Sen Univ, Zhongshan Sch Med, Dept Pharmacol, 74 Zhongshan Rd 2, Guangzhou 510080, Guangdong, Peoples R China. EM limt@mail.sysu.edu.cn OI Ma, Shanshan/0000-0002-3004-9468 FU National Natural Science Foundation of China [U0632006, 30870786, 30629002, 30831160511] FX This work was supported by National Natural Science Foundation of China grants U0632006, 30870786, 30629002, and 30831160511. NR 56 TC 39 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 1 PY 2009 VL 29 IS 9 BP 2431 EP 2442 DI 10.1128/MCB.01344-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432AV UT WOS:000265106800009 PM 19255142 ER PT J AU Gavard, J Hou, X Qu, Y Masedunskas, A Martin, D Weigert, R Li, XR Gutkind, JS AF Gavard, Julie Hou, Xu Qu, Yi Masedunskas, Andrius Martin, Daniel Weigert, Roberto Li, Xuri Gutkind, J. Silvio TI A Role for a CXCR2/Phosphatidylinositol 3-Kinase gamma Signaling Axis in Acute and Chronic Vascular Permeability SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL PERMEABILITY; MACULAR DEGENERATION; NEUTROPHIL MIGRATION; TISSUE-INJURY; SRC ACTIVITY; VE-CADHERIN; ANGIOGENESIS; INHIBITION; MICE; CELLS AB Most proangiogenic polypeptide growth factors and chemokines enhance vascular permeability, including vascular endothelial growth factor (VEGF), the main target for anti-angiogenic-based therapies, and interleukin-8 (IL-8), a potent proinflammatory mediator. Here, we show that in endothelial cells IL-8 initiates a signaling route that converges with that deployed by VEGF at the level of the small GTPase Rac1 and that both act through the p21-activated kinase to promote the phosphorylation and internalization of VE-cadherin. However, whereas VEGF activates Rac1 through Src-related kinases, IL-8 specifically signals to Rac1 through its cognate G protein-linked receptor, CXCR2, and the stimulation of the phosphatidylinositol 3-kinase gamma (PI3K gamma) catalytic isoform, thereby providing a specific molecular targeted intervention in vascular permeability. These results prompted us to investigate the potential role of IL-8 signaling in a mouse model for retinal vascular hyperpermeability. Importantly, we observed that IL-8 is upregulated upon laser-induced retinal damage, which recapitulates enhanced vascularization, leakage, and inflammatory responses. Moreover, blockade of CXCR2 and PI3K gamma was able to limit neovascularization and choroidal edema, as well as macrophage infiltration, therefore contributing to reduce retinal damage. These findings indicate that the CXCR2 and PI3K gamma signaling pathway may represent a suitable target for the development of novel therapeutic strategies for human diseases characterized by vascular leakage. C1 [Gavard, Julie; Masedunskas, Andrius; Martin, Daniel; Weigert, Roberto; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Hou, Xu; Qu, Yi; Li, Xuri] NEI, Unit Vasc Retinal Neurobiol Res, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. [Masedunskas, Andrius; Weigert, Roberto] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Gavard, Julie] Univ Paris 05, CNRS, INSERM, Inst Cochin,UMR8104,U567, F-75014 Paris, France. RP Gavard, J (reprint author), Univ Paris 05, CNRS, INSERM, Inst Cochin,UMR8104,U567, 22 Rue Mech, F-75014 Paris, France. EM julie.gavard@inserm.fr; sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Gavard, Julie/I-5487-2012 OI Gavard, Julie/0000-0002-7985-9007 FU NIH; National Institute of Dental and Craniofacial Research; Centre National de la Recherche Scientifique (CNRS); Ligue Nationale contre le Cancer Region Ile-de-France FX We declare we have no competing financial interests. NR 54 TC 40 Z9 41 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY 1 PY 2009 VL 29 IS 9 BP 2469 EP 2480 DI 10.1128/MCB.01304-08 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432AV UT WOS:000265106800012 PM 19255141 ER PT J AU Papadimou, E Moiana, A Goffredo, D Koch, P Bertuzzi, S Brustle, O Cattaneo, E Conti, L AF Papadimou, Evangelia Moiana, Alessia Goffredo, Donato Koch, Philipp Bertuzzi, Stefano Bruestle, Oliver Cattaneo, Elena Conti, Luciano TI p66(ShcA) adaptor molecule accelerates ES cell neural induction SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Neural induction; Embryonic stem cell; Shc molecules; beta-catenin ID EMBRYONIC STEM-CELLS; GLYCOGEN-SYNTHASE KINASE-3; OXIDATIVE STRESS; BETA-CATENIN; SIGNALING PATHWAY; MAMMALIAN BRAIN; SRC HOMOLOGY; WNT PATHWAY; C-ELEGANS; LIFE-SPAN AB SHC genes codify for a family of adaptor molecules comprising four genes. Previous data have implicated the Shc(s) molecule. s in stem cell division and differentiation. Specifically, the p66(ShcA) isoform has been found to contribute to longevity and resistance from oxidative stress. Here we report that p66(ShcA) is up-regulated during in vitro neural induction in embryonic stem cells. p66(ShcA) over-expression in ES cells reduces GSK-3 beta kinase activation and increases beta-catenin stabilization and its transcriptional activity. p66(ShcA) over-expression results in ES cells undergoing an anticipated neural induction and accelerated neuronal differentiation. Similar effects are obtained in human ES cells overexpressing p66(ShcA). This Study reveals a role for p66(ShcA) in the modulation of Wnt/beta-catenin pathway and in ES cell neuralization which is consistent between mouse and human. (C) 2009 Elsevier Inc. All rights reserved. C1 [Papadimou, Evangelia; Moiana, Alessia; Goffredo, Donato; Cattaneo, Elena; Conti, Luciano] Univ Milan, Ctr Stem Cell Res, I-20133 Milan, Italy. [Papadimou, Evangelia; Moiana, Alessia; Goffredo, Donato; Cattaneo, Elena; Conti, Luciano] Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. [Koch, Philipp; Bruestle, Oliver] Univ Bonn, Inst Reconstruct Neurobiol, Life & Brain Ctr, D-5300 Bonn, Germany. [Bertuzzi, Stefano] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA. RP Cattaneo, E (reprint author), Univ Milan, Ctr Stem Cell Res, Via Balzaretti 9, I-20133 Milan, Italy. EM elena.cattaneo@unimi.it RI Conti, Luciano/H-4184-2012; Koch, Philipp/M-1186-2016; OI Conti, Luciano/0000-0002-2050-9846; Bertuzzi, Stefano/0000-0003-4562-3626; CATTANEO, ELENA/0000-0002-0755-4917; Koch, Philipp/0000-0003-3713-8786 FU EuroStemCell [LSHB-CT-2003-503005]; ESTOOLS [LSHG-CT-2006-018739]; Istituto Superiore di Sanita-Programma Nazionale sulle Cellule Staminali [CS117]; Telethon [GP0457Y02]; Telethon Foundation [TCP99018] FX This research was supported by funding from EuroStemCell (FP6, LSHB-CT-2003-503005, European Union) to EC and OB. Partial funding was obtained from ESTOOLS (FP6, LSHG-CT-2006-018739 European Union) to EC and OB, from Istituto Superiore di Sanita-Programma Nazionale sulle Cellule Staminali (CS117 Italy) to EC, Telethon (Project #GP0457Y02) to LC and Telethon Foundation to SB (Grant # TCP99018). We thank Catarina Ramos and Roberta Azzarelli for help with cell culture and PCR assays, Prof. Austin Smith for the mouse 46C and IOUD2 ES cell lines and Dr. Josh Brickman for the gift of luciferase plasmids. NR 54 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2009 VL 41 IS 1 BP 74 EP 84 DI 10.1016/j.mcn.2009.01.010 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 440QV UT WOS:000265715700008 PM 19386228 ER PT J AU Sun, JX Mullikin, JC Patterson, N Reich, DE AF Sun, James X. Mullikin, James C. Patterson, Nick Reich, David E. TI Microsatellites Are Molecular Clocks That Support Accurate Inferences about History SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE microsatellite evolution; molecular clocks; coalescent time; average square distance; F(ST); SNP ascertainment bias ID STEPWISE MUTATION MODEL; HUMAN GENOME; GENETIC DISTANCES; HUMAN-POPULATIONS; ALLELE FREQUENCIES; COALESCENCE TIMES; TANDEM REPEATS; MODERN HUMANS; LOCI; EVOLUTION AB Microsatellite length mutations are often modeled using the generalized stepwise mutation process, which is a type of random walk. If this model is sufficiently accurate, one can estimate the coalescence time between alleles of a locus after a mathematical transformation of the allele lengths. When large-scale microsatellite genotyping first became possible, there was substantial interest in using this approach to make inferences about time and demography, but that interest has waned because it has not been possible to empirically validate the clock by comparing it with data in which the mutation process is well understood. We analyzed data from 783 microsatellite loci in human populations and 292 loci in chimpanzee populations, and compared them with up to one gigabase of aligned sequence data, where the molecular clock based upon nucleotide substitutions is believed to be reliable. We empirically demonstrate a remarkable linearity (r(2) > 0.95) between the microsatellite average square distance statistic and sequence divergence. We demonstrate that microsatellites are accurate molecular clocks for coalescent times of at least 2 million years (My). We apply this insight to confirm that the African populations San, Biaka Pygmy, and Mbuti Pygmy have the deepest coalescent times among populations in the Human Genome Diversity Project. Furthermore, we show that microsatellites support unbiased estimates of population differentiation (F(ST)) that are less subject to ascertainment bias than single nucleotide polymorphism (SNP) F(ST). These results raise the prospect of using microsatellite data sets to determine parameters of population history. When genotyped along with SNPs, microsatellite data can also be used to correct for SNP ascertainment bias. C1 [Sun, James X.; Patterson, Nick; Reich, David E.] MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Sun, James X.; Reich, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Mullikin, James C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Sun, James X.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Sun, James X.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Sun, JX (reprint author), MIT & Harvard, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. EM xinsun@mit.edu FU Burroughs Wellcome Career Development Award in the Biomedical Sciences; NIH; National Human Genome Research Institute, NIH FX We thank Alon Keinan for his suggestions about the design of the SNP ascertainment bias simulations. D. R. was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences. J.S. was supported by the Bioinformatics and Integrative Genomics Ph.D. training grant by NIH. J.C.M. was supported by the Intramural Research Program of the National Human Genome Research Institute, NIH. We are grateful to Nicole Stange-Thomann and Julie Neubauer for preparing the Reduced Representation Shotgun data. NR 60 TC 47 Z9 51 U1 1 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAY PY 2009 VL 26 IS 5 BP 1017 EP 1027 DI 10.1093/molbev/msp025 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 434KQ UT WOS:000265274000006 PM 19221007 ER PT J AU Rozenberg, J Rishi, V Orosz, A Moitra, J Glick, A Vinson, C AF Rozenberg, Julian Rishi, Vikas Orosz, Andras Moitra, Jaideep Glick, Adam Vinson, Charles TI Inhibition of CREB Function in Mouse Epidermis Reduces Papilloma Formation SO MOLECULAR CANCER RESEARCH LA English DT Article ID ELEMENT-BINDING PROTEIN; CAMP-RESPONSIVE ELEMENT; TRANSCRIPTION FACTORS; GENE-EXPRESSION; CELL-SURVIVAL; DNA-BINDING; TUMOR PROMOTION; BENIGN-TUMORS; UP-REGULATION; CIS-ELEMENTS AB We used a double transgenic tetracycline system to conditionally express A-CREB, a dominant negative protein that prevents the DNA binding and function of cAMP-responsive element binding protein (CREB) family members, in mouse basal epidermis using the keratin 5 promoter. There was no phenotype in the adult. However, following a 7,12-dimethylbenz(a)anthracene (DMBA)/phorbol-12-myristate-13-acetate two-stage skin carcinogenesis experiment, A-CREB-expressing epidermis develop 5-fold fewer papillomas than wild-type controls. However, A-CREB expression one month after DMBA treatment does not prevent papilloma formation, suggesting that CREB functions at an early stage of papilloma formation. Oncogenic H-Ras genes with A-T mutations in codon 61 were found in wild-type skin but not in A-CREB-expressing skin 2 days after DMBA treatment, suggesting that A-CREB either prevents DMBA mutagenesis or kills oncogenic H-Ras cells. In primary keratinocyte cultures, A-CREB expression induced apoptosis of v-Ras(Ha)-infected cells and suppressed the expression of cell cycle proteins cyclin B1 and cyclin D1. These results suggest that inhibiting CREB function is a valuable cancer prevention strategy. (Mol Cancer Res 2009;7(5):654-64) C1 [Rozenberg, Julian; Rishi, Vikas; Orosz, Andras; Moitra, Jaideep; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Moitra, Jaideep] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Glick, Adam] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, 37 Convent Dr,Room 2D24, Bethesda, MD 20892 USA. EM Vinsonc@mail.nih.gov NR 53 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2009 VL 7 IS 5 BP 654 EP 664 DI 10.1158/1541-7786.MCR-08-0011 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 448TD UT WOS:000266284000005 PM 19435810 ER PT J AU Wang, B Khachigian, LM Esau, L Birrer, MJ Zhao, XC Parker, MI Hendricks, DT AF Wang, Bo Khachigian, Levon M. Esau, Luke Birrer, Michael J. Zhao, Xiaohang Parker, M. Iqbal Hendricks, Denver T. TI A Key Role for Early Growth Response-1 and Nuclear Factor-kappa B in Mediating and Maintaining GRO/CXCR2 Proliferative Signaling in Esophageal Cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR EGR-1; GENE-EXPRESSION; PROSTATE-CANCER; CARCINOMA-CELLS; TARGET GENES; TUMOR-GROWTH; ACTIVATION; BETA; LOCALIZATION; DIFFERENTIATION AB Although early growth response-1 (EGR-1) has been shown as a key transcription factor in controlling cell growth, proliferation, differentiation, and angiogenesis, its role in the development of esophageal cancer is poorly understood despite the high frequency of this disease in many parts of the world. Here, immunohistochemistry showed that EGR-1 is overexpressed in 80% of esophageal tumor tissues examined. Furthermore, EGR-1 is constitutively expressed in all esophageal cancer cell lines analyzed. Esophageal squamous carcinoma WHCO1 cells stably transfected with EGR-1 short hairpin RNA displayed a 55% reduction in EGR-1 protein levels, 50% reduction in cell proliferation, a 50% reduction in cyclin-dependent kinase 4 levels, and a 2-fold induction in p27(Kip1) levels associated with a G(2)-M cell cycle arrest. EGR-1 knockdown also caused a marked induction in I kappa B alpha expression, an effect also observed in GRO beta RNA interference-expressing WHCO1 cells, because EGR-1 lies downstream of GRO/CXCR2 signaling. Furthermore, p65 mRNA levels were also reduced in cells treated with either short hairpin RNA EGR-1 or small interfering RNA EGR-1. Immunohistochemical analysis indicated that p65 is elevated in 78% (n = 61) of esophageal tumor sections analyzed. Moreover, nuclear factor-kappa B inhibition with either sodium salicylate or p65 RNA interference led to a significant reduction in GRO alpha and GRO beta expression. These results indicate that EGR-1 and nuclear factor-kappa B mediate GRO/CXCR2 proliferative C1 [Wang, Bo; Esau, Luke; Parker, M. Iqbal; Hendricks, Denver T.] Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Div Med Bichem, ZA-7925 Cape Town, South Africa. [Khachigian, Levon M.] Univ New S Wales, Ctr Vasc Res, Sydney, NSW, Australia. [Birrer, Michael J.] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhao, Xiaohang] CAMS, Canc Inst & Hosp, Beijing, Peoples R China. [Zhao, Xiaohang] Natl Lab Mol Oncol, PUMC, Beijing, Peoples R China. RP Hendricks, DT (reprint author), Univ Cape Town, Fac Hlth Sci, Inst Infect Dis & Mol Med, Div Med Bichem, Anzio Rd, ZA-7925 Cape Town, South Africa. EM Denver.Hendricks@uct.ac.za FU Medical Research Council (South Africa); University of Cape Town; NRF Joint China/South Africa Science and Technology Agreement GUN [2075479]; NIH [5RO1 CA 112020] FX Grant support: Medical Research Council (South Africa) and University of Cape Town, NRF Joint China/South Africa Science and Technology Agreement GUN 2075479, and NIH grant 5RO1 CA 112020. NR 35 TC 27 Z9 30 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAY PY 2009 VL 7 IS 5 BP 755 EP 764 DI 10.1158/1541-7786.MCR-08-0472 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 448TD UT WOS:000266284000014 PM 19435811 ER PT J AU Pommier, Y Cushman, M AF Pommier, Yves Cushman, Mark TI The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives SO MOLECULAR CANCER THERAPEUTICS LA English DT Article CT 13th International Charles Heidelberger Symposium CY SEP 06-08, 2007 CL New York Univ, Canc Inst, New York, NY HO New York Univ, Canc Inst ID DNA COVALENT COMPLEX; BIOLOGICAL EVALUATION; CLEAVAGE COMPLEXES; NITRATED INDENOISOQUINOLINES; CAMPTOTHECIN RESISTANCE; MJ-III-65 NSC-706744; ANTICANCER ACTIVITY; HISTONE H2AX; CELL-LINE; DESIGN AB Because camptothecins are effective against previously resistant tumors and are the only class of topoisomerase I (Top1) inhibitors approved for cancer treatment, we developed the indenoisoquinolines. Like camptothecins, the indenoisoquinolines selectively trap Top1-DNA cleavage complexes and have been cocrystallized with the Top1-DNA cleavage complexes. Indenoisoquinolines show antitumor activity in animal models. They have several advantages over the camptothecins: (a) They are synthetic and chemically stable. (b) The Top1 cleavage sites trapped by the indenoisoquinolines have different genomic locations, implying differential targeting of cancer cell genomes. (c) The Top1 cleavage complexes trapped by indenoisoquinolines are more stable, indicative of prolonged drug action. (d) They are seldom or not used as substrates for the multidrug resistance efflux pumps (ABCG2 and MDR-1). Among the >400 indenoisoquinolines synthesized and evaluated, three have been retained as leads for clinical development by the National Cancer Institute: NSC 706744, NSC 725776 (Indimitecan), and NSC 724998 (Indotecan). The trapping of Top1 cleavage complexes by indenoisoquinolines in cells results in the rapid and sustained phosphorylation of histone H2AX (gamma-H2AX). We discuss the use of gamma-H2AX as a pharmacodynamic biomarker for the clinical development of the indenoisoquinolines. [Mol Cancer Ther 2009;8(5):1008-14] C1 [Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cushman, Mark] Purdue Univ, Dept Med Chem, Lafayette, IN USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Room 5068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov; cushman@pharmacy.purdue.edu FU Intramural NIH HHS [Z01 BC006161-24]; NCI NIH HHS [U01 CA089566, UO1 CA89566] NR 63 TC 76 Z9 79 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2009 VL 8 IS 5 BP 1008 EP 1014 DI 10.1158/1535-7163.MCT-08-0706 PG 7 WC Oncology SC Oncology GA 447KL UT WOS:000266189900004 PM 19383846 ER PT J AU Ceresa, C Giovannetti, E Voortman, J Laan, AC Honeywell, R Giaccone, G Peters, GJ AF Ceresa, Cecilia Giovannetti, Elisa Voortman, Jens Laan, Adrie C. Honeywell, Richard Giaccone, Giuseppe Peters, Godefridus J. TI Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article CT 13th International Charles Heidelberger Symposium CY SEP 06-08, 2007 CL New York Univ, Canc Inst, New York, NY HO New York Univ, Canc Inst ID PROTEASOME INHIBITOR BORTEZOMIB; ADVANCED SOLID TUMORS; PHASE-I TRIAL; PLUS CISPLATIN; COMBINATION; LINES; DEOXYCYTIDINE; PACLITAXEL; RESISTANCE; APOPTOSIS AB Bortezomib combination with gemcitabine/cisplatin in patients with advanced tumors, predominantly non-small cell lung cancer (NSCLC), showed an unexpected transient drop in the deoxycytidine plasma levels, a marker for gemcitabine activity. This study investigates the pharmacokinetic/pharmacodynamic effect of bortezomib on gemcitabine in NSCLC and peripheral blood mononuclear cells (PBMC). Gemcitabine metabolites, including difluoro-dCTP (dFdCTP), were studied in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients and from volunteers and NSCLC cells (H460 and SW1573) exposed to 4 h simultaneous or sequential treatments of gemcitabine (50 mu mol/L, 4 h) and bortezomib (100 nmol/L, 2 h). Gemcitabine total phosphate levels measured by liquid chromatography-tandem mass spectrometry in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients were strongly reduced after 90 min (-82.2%) up to 4 h post-gemcitabine infusion compared with gemcitabine/cisplatin-treated patients. Accordingly, bortezomib/gemcitabine combinations reduced dFdCTP in PBMCs treated ex vivo. Surprisingly, differential effects were observed in NSCLC cells. dFdCTP decreased after 4 h following gemcitabine removal in H460 but continued to increase for 24 h in SW1573. However, dFdCTP significantly increased (2-fold) in both cell lines in the bortezomib -> gemcitabine exposure, coinciding with a major reduction in cell growth compared with single drugs, and the highest increase of deoxycytidine kinase expression, possibly mediated via E2F-1. Bortezomib affects differently gemcitabine pharmacokinetics/pharmacodynamics in PBMCs and NSCLC cells, suggesting that PBMCs are not adequate to evaluate the anticancer activity of bortezomib/gemcitabine combinations. The bortezomib -> gemcitabine/cisplatin schedule appeared a safe and active combination for the treatment of advanced NSCLC and the bortezomib -> gemcitabine was the most cytotoxic combination in NSCLC cells. The increase of deoxycytidine kinase and dFdCTP might contribute to this synergistic interaction and supports its further clinical investigation. [Mol Cancer Ther 2009;8(5):1026-36] C1 [Ceresa, Cecilia; Giovannetti, Elisa; Voortman, Jens; Laan, Adrie C.; Honeywell, Richard; Peters, Godefridus J.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. [Ceresa, Cecilia] Univ Milano Bicocca, Dept Neurosci & Biomed Technol, Monza, Italy. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Giovannetti, E (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, CCA 1-52,De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM elisa.giovannetti@gmail.com RI Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Giovannetti, Elisa/0000-0002-7565-7504 NR 50 TC 11 Z9 11 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2009 VL 8 IS 5 BP 1026 EP 1036 DI 10.1158/1535-7163.MCT-08-0700 PG 11 WC Oncology SC Oncology GA 447KL UT WOS:000266189900006 PM 19383850 ER PT J AU Feng, Y Xiao, XD Zhu, ZY Streaker, E Ho, M Pastan, I Dimitrov, DS AF Feng, Yang Xiao, Xiaodong Zhu, Zhongyu Streaker, Emily Ho, Mitchell Pastan, Ira Dimitrov, Dimiter S. TI A novel human monoclonal antibody that binds with high affinity to mesothelin-expressing cells and kills them by antibody-dependent cell-mediated cytotoxicity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID PANCREATIC-CANCER; OVARIAN-CANCER; SERUM MESOTHELIN; PHAGE DISPLAY; LUNG-CANCER; IMMUNOTOXIN; MARKER; TARGET; TUMORS AB Mesothelin is a potential new target for cancer immunotherapy because it is present at relatively low levels only in mesothelial cells of pleura, peritoneum, and pericardium of healthy people, but is significantly elevated in a number of tumors, including mesothelioma, ovarian, pancreatic, and lung cancers. However, all currently available antibodies against mesothelin are either murine or chimeric, which could limit their use because of increased likelihood of immunogenicity compared with fully human antibodies. Here, we report the identification and characterization of a novel fully human monoclonal antibody, m912, which was isolated from a human Fab library by panning against recombinant mesothelin. This antibody in scFv, Fab, and IgG1 formats bound specifically and with high affinity (equilibrium dissociation constant in the nmol/L range) to cell surf ace-associated human mesothelin and to recombinant mesothelin. It specifically lysed cancer cells engineered to express mesothelin in the presence of peripheral blood mononuclear cells isolated from healthy donors most likely by antibody-dependent cellular cytotoxicity. M912 is the first reported fully human monoclonal antibody to mesothelin, which has potential for cancer treatment and diagnosis. [Mol Cancer Ther 2009;8(5):1113-8] C1 [Feng, Yang; Xiao, Xiaodong; Zhu, Zhongyu; Streaker, Emily; Dimitrov, Dimiter S.] NCI, Ctr Canc Res, Nanobiol Program, Prot Interact Grp,NIH, Frederick, MD 21702 USA. [Zhu, Zhongyu] NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21702 USA. [Ho, Mitchell; Pastan, Ira] Natl Canc Inst Frederick, Mol Biol Lab, CCR, NIH, Bethesda, MD USA. RP Feng, Y (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Prot Interact Grp,NIH, Bldg 469,Rm 139, Frederick, MD 21702 USA. EM yfeng@ncifcrf.gov; dimitrov@ncifcrf.gov RI Ho, Mitchell/F-5059-2015 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; National Cancer Institute, NIH [N01-CO-12400] FX Grant support: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400. NR 24 TC 28 Z9 30 U1 3 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2009 VL 8 IS 5 BP 1113 EP 1118 DI 10.1158/1535-7163.MCT-08-0945 PG 6 WC Oncology SC Oncology GA 447KL UT WOS:000266189900015 PM 19417159 ER PT J AU Su, DM Zhang, QY Wang, XX He, P Zhu, YLJ Zhao, JX Rennert, OM Su, YA AF Su, David M. Zhang, Qiuyang Wang, Xuexi He, Ping Zhu, Yuelin Jack Zhao, Jianxiong Rennert, Owen M. Su, Yan A. TI Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RANDOMIZED PHASE-III; METASTASIS; DACARBAZINE; UACC903(+6); TUMORIGENICITY; MICROARRAY; MICE AB Human malignant melanoma has poor prognosis because of resistance to apoptosis and therapy. We describe identification of the expression profile of 1,037 mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant melanoma cell lines and 3 normal melanocyte controls using recently developed hMitChip3 cDNA micro-arrays. Unsupervised hierarchical clustering analysis of 1,037 informative genes, and 84 survival-apoptosis genes, classified these malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three hundred fifty-five of 1,037 (34.2%) genes displayed significant (P:5 0.030; false discovery rate <= 3.68%) differences ( +/->= 2.0-fold) in average expression, with 197 genes higher and 158 genes lower in type A than in type B. Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the significant (P < 0.001; false discovery rate < 0.15%) difference. Antiapoptotic (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1) genes expressed at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant [HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, PDCD5, HTRA2 SEPT4, TNFSF10, and PRODH) genes expressed at lower levels in type A than in type B. Microarray data were validated by quantitative reverse transcription-PCR. These results showed the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes, which may prove useful for development of new molecular targets for therapeutic intervention and novel diagnostic biomarkers for treatment and prognosis of malignant melanoma. [Mol Cancer Ther 2009;8(5):1292-1304] C1 [Su, David M.; Zhang, Qiuyang; Wang, Xuexi; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Su, David M.; Zhang, Qiuyang; Wang, Xuexi; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [Wang, Xuexi; Zhao, Jianxiong] Lanzhou Univ, Sch Med Sci, Inst Chinese Western Integrat Med, Lanzhou 730000, Gansu, Peoples R China. [He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA. [Rennert, Owen M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Clin Gen, NIH, Bethesda, MD USA. [Zhu, Yuelin Jack] NCI Frederick, Sci Applicat Int Corp Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD USA. RP Su, YA (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Room 555,2300 1 St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU Intramural NIH HHS [Z01 HD008868-01]; PHS HHS [NIH-NIDDK-06-925] NR 35 TC 26 Z9 26 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2009 VL 8 IS 5 BP 1292 EP 1304 DI 10.1158/1535-7163.MCT-08-1030 PG 13 WC Oncology SC Oncology GA 447KL UT WOS:000266189900033 PM 19383853 ER PT J AU Bae, DS Blazanin, N Licata, M Lee, J Glick, AB AF Bae, Dong-Soon Blazanin, Nicholas Licata, Mathew Lee, Jessica Glick, Adam B. TI Tumor Suppressor and Oncogene Actions of TGF beta 1 Occur Early in Skin Carcinogenesis and Are Mediated by Smad3 SO MOLECULAR CARCINOGENESIS LA English DT Article DE TGF beta 1; ras oncogene; skin carcinogenesis; Smad3; keratinocytes; transcriptional profiling ID TRANSFORMING-GROWTH-FACTOR; TGF-BETA RECEPTOR; EXTRACELLULAR-MATRIX; CHEMICAL CARCINOGENESIS; KERATINOCYTE DIFFERENTIATION; EPIDERMAL-KERATINOCYTES; MALIGNANT CONVERSION; TRANSGENIC MICE; EXPRESSION; MOUSE AB Interactions between TGF beta 1 and ras signaling pathways play an important role in cancer development. Here we show that in primary mouse keratinocytes, v-ras(Ha) does not block the early biochemical events of TGF beta 1 signal transduction but does alter global TGF beta 1 mediated gene expression in a gene specific manner. Expression of Smad3 dependent TGF beta 1 early response genes and the TGF beta 1 cytostatic gene expression response were not altered by v-ras(Ha) consistent with an intact TGF beta 1 growth arrest. However, TGF beta 1 and v-ras(Ha) cause significant alteration in genes regulating matrix remodeling as the TGF beta 1 induction of extracellular matrix genes was blocked by v-ras(Ha) but specific matrix proteases associated with cancer progression were elevated. Smad3 deletion in keratinocytes repressed normal differentiation maker expression and caused expression of Keratin 8 a simple epithelial keratin and marker of malignant conversion. Smad3 was required for the TGF beta 1 cytostatic response in v-ras(Ha) keratinocytes, but also for protease induction, keratinocyte attachment and migration. These results show that pro-oncogenic activities of TGF beta 1 can occur early in carcinogenesis before loss of its tumor suppressive function and that selective regulation rather than complete inactivation of Smad3 function may be crucial for tumor progression. (C) 2008 Wiley-Liss, Inc. C1 [Blazanin, Nicholas; Licata, Mathew; Glick, Adam B.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Bae, Dong-Soon; Lee, Jessica] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Glick, AB (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. FU Intramural NIH HHS; NCI NIH HHS [R01 CA122109-01, CA122109, R01 CA122109] NR 50 TC 13 Z9 14 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAY PY 2009 VL 48 IS 5 BP 441 EP 453 DI 10.1002/mc.20482 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 444AJ UT WOS:000265951800005 PM 18942075 ER PT J AU Wang, DQ Xia, XM Liu, Y Oetting, A Walker, RL Zhu, YL Meltzer, P Cole, PA Shi, YB Yen, PM AF Wang, Dongqing Xia, Xianmin Liu, Ying Oetting, Alexis Walker, Robert L. Zhu, Yuelin Meltzer, Paul Cole, Philip A. Shi, Yun-Bo Yen, Paul M. TI Negative Regulation of TSH alpha Target Gene by Thyroid Hormone Involves Histone Acetylation and Corepressor Complex Dissociation SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROTROPIN-BETA GENE; STIMULATING HORMONE; IN-VIVO; RESPONSIVE PROMOTERS; ESTROGEN-RECEPTOR; SUBUNIT GENE; TATA BOX; TRANSCRIPTION; RECRUITMENT; REPRESSION AB Currently, little is known about histone modifications and molecular mechanisms of negatively regulated transcription. In pituitary cells, thyroid hormone (T(3)) decreased transcription, and surprisingly increased histone acetylation, of TSH alpha promoter. This increase was mediated directly by thyroid hormone receptor. Histone acetylation of H3K9 and H3K18 sites, two modifications usually associated with transcriptional activation, occur in negative regulation of TSH alpha promoter. T(3) also caused release of a corepressor complex composed of histone deacetylase 3 (HDAC3), transducin beta-like protein 1, and nuclear receptor coprepressor (NCoR)/silencing mediator for retinoic and thyroid hormone receptor from TSH alpha promoter in chromatin immunoprecipitation assays. NCoR and HDAC3 overexpression selectively increased ligand-independent basal transcription. Two histone acetyltransferase inhibitors increased overall transcription but did not abrogate negative regulation or NCoR/HDAC3 complex release by T(3). Chromatin immunoprecipitation analyses of an endogenous positively regulated target gene showed increased histone acetylation and corepressor complex release with T(3) treatment. Finally, microarray analyses suggested there is a subset of negatively regulated genes with increased histone acetylation. These findings demonstrate the critical role of NCoR/HDAC3 complex in negative regulation of TSH alpha gene expression and show that similar complexes and overlapping epigenetic modifications can participate in both negative and positive transcriptional regulation. (Molecular Endocrinology 23: 600-609, 2009) C1 [Wang, Dongqing; Xia, Xianmin; Yen, Paul M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol, Baltimore, MD 21224 USA. [Cole, Philip A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA. [Liu, Ying] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Oetting, Alexis; Shi, Yun-Bo] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. [Walker, Robert L.; Zhu, Yuelin; Meltzer, Paul] Natl Canc Inst, Genet Branch, Bethesda, MD 20892 USA. RP Yen, PM (reprint author), Duje NUS Grad Med Sch, Cardiovasc & Metab Program, 2 Jalan Bukit Merah, Singapore 169547, Singapore. EM paul.yen@duke-nus.edu.sg FU National Institute of Child Health and Human Development; National Institutes of Health; National Cancer Institute; [R01 NIDDK 1R01DK069899] FX This research was supported in part by grants from the Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health (to Y.S.) and National Cancer Institute (to P. M.) and by R01 NIDDK 1R01DK069899 (to P.M.Y.). NR 43 TC 22 Z9 22 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 2009 VL 23 IS 5 BP 600 EP 609 DI 10.1210/me.2008-0389 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 438YP UT WOS:000265593100003 PM 19196836 ER PT J AU Mabley, JG Pacher, P Szabo, C AF Mabley, Jon G. Pacher, Pal Szabo, Csaba TI Activation of the Cholinergic Antiinflammatory Pathway Reduces Ricin-Induced Mortality and Organ Failure in Mice SO MOLECULAR MEDICINE LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; SYSTEMIC INFLAMMATORY RESPONSE; HEMOLYTIC-UREMIC SYNDROME; MAP KINASE PATHWAY; VAGUS NERVE; KAPPA-B; EXPERIMENTAL SEPSIS; BOWEL-DISEASE; MURINE MODEL; MOUSE MODEL AB Exposure to ricin, either by accident through ingestion of castor oil plant seeds or intentionally through its use as a bioweapon, invariably leads to multiple organ damage and death. Currently there is only a vaccine in advanced development to ricin, but no other antidote. Ricin causes systemic inflammation with increased proinflammatory cytokine release and subsequent multiple organ failure, particularly kidney and liver dysfunction. Activation of the cholinergic antiinflammatory pathway, specifically through the alpha7 nicotinic acetylcholine receptor (either indirectly through vagus nerve stimulation or directly through nicotine treatment) reduces proinflammatory gene expression. This activation also increases release of proinflammatory chemokines and cytokines, and has proven effective in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against ricin toxicity in mice. Male Balb/c mice exposed to ricin had increased serum levels of the inflammatory cytokine tumor necrosis factor-a and markers of both kidney (blood urea nitrogen, creatine) and liver (alanine tranaminase) dysfunction, with a subsequent increase in mortality. Nicotine administration 2 h after ricin injection significantly delayed and reduced ricin-induced mortality, an effect coupled with reduced serum levels of tumor necrosis factor-a and markers of kidney and liver dysfunction. Both the kidney and liver had markedly increased cellular oxidative stress following ricin exposure, an effect attenuated by nicotine administration. In conclusion, these data demonstrate that in cases of ricin poisoning, activation of the cholinergic antiinflammatory pathway may prove beneficial by reducing organ damage, delaying mortality and allowing for a greater chance of survival. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org C1 [Mabley, Jon G.] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England. [Pacher, Pal] NIH, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD 20892 USA. [Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX USA. RP Mabley, JG (reprint author), Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England. EM j.g.Mabley@brighton.ac.uk RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999] NR 51 TC 17 Z9 17 U1 0 U2 3 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD MAY-JUN PY 2009 VL 15 IS 5-6 BP 166 EP 172 DI 10.2119/molmed.2008.00105 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 575CU UT WOS:000276043700007 PM 19209239 ER PT J AU Mandin, P Gottesman, S AF Mandin, Pierre Gottesman, Susan TI A genetic approach for finding small RNAs regulators of genes of interest identifies RybC as regulating the DpiA/DpiB two-component system SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI PLASMIDS; NONCODING RNAS; TRANSCRIPTIONAL ACTIVATOR; ACID RESISTANCE; SOS RESPONSE; TARGETS; PREDICTION; BACTERIA; BINDING; HFQ AB In Escherichia coli, the largest class of small regulatory RNAs binds to the RNA chaperone Hfq and regulates the stability and/or translation of specific mRNAs. While recent studies have shown that some mRNAs could be subject to post-transcriptional regulation by sRNAs (e. g. mRNAs found by co-immunoprecipitation with Hfq), no method has yet been described to identify small RNAs that regulate them. We developed a method to easily make translational fusions of genes of interest to the lacZ reporter gene, under the control of a PBAD-inducible promoter. A multicopy plasmid library of the E. coli genome can then be used to screen for small RNAs that affect the activity of the fusion. This screening method was first applied to the dpiB gene from the dpiBA operon, which encodes a two-component signal transduction system involved in the SOS response to beta-lactams. One small RNA, RybC, was found to negatively regulate the expression of dpiB. Using mutants in the dpiB-lacZ fusion and compensatory mutations in the RybC sRNA, we demonstrate that RybC directly base pairs with the dpiBA mRNA. C1 [Mandin, Pierre; Gottesman, Susan] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU NIH; National Cancer Institute, Center for Cancer Research FX We thank members of the laboratory and Gisela Storz for comments on the manuscript and advice and discussion throughout the work. We thank P. Valentin-Hansen for sharing unpublished information, and thank S. N. Cohen and J. Opdyke for strains and advice. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 42 TC 64 Z9 64 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2009 VL 72 IS 3 BP 551 EP 565 DI 10.1111/j.1365-2958.2009.06665.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 436JN UT WOS:000265410500001 PM 19426207 ER PT J AU DeKeyser, JG Stagliano, MC Auerbach, SS Prabhu, KS Jones, AD Omiecinski, CJ AF DeKeyser, Joshua G. Stagliano, Michael C. Auerbach, Scott S. Prabhu, K. Sandeep Jones, A. Daniel Omiecinski, Curtis J. TI Di(2-ethylhexyl) phthalate Is a Highly Potent Agonist for the Human Constitutive Androstane Receptor Splice Variant CAR2 SO MOLECULAR PHARMACOLOGY LA English DT Article ID PREGNANE-X-RECEPTOR; LIGAND-BINDING; METABOLISM; ALPHA; LIVER; ACTIVATION; EXPRESSION; EXPOSURE; DI-(2-ETHYLHEXYL)PHTHALATE; IDENTIFICATION AB The human constitutive androstane receptor (CAR, CAR1) regulates the expression of genes involved in xenobiotic metabolism in the liver. The CAR gene uses multiple alternative splicing events during pre-mRNA processing, thereby enhancing the CAR transcriptome. Previous reports have identified two prominent human CAR variants, CAR2 and CAR3, that possess four- and five-amino acid insertions in their ligand binding domains, respectively. Unlike the constitutively active reference form of the receptor, we now demonstrate that CAR2 is a ligand-activated receptor and comprises approximately 30% of the reference transcript level in human liver tissues in human hepatocytes. Furthermore, we identify the common plasticizer, di(2-ethylhexyl) phthalate (DEHP), as a highly potent and uniquely selective agonist of CAR2. Results from reporter transactivation and mammalian two-hybrid assays reveal that DEHP activates CAR2 at low nanomolar concentrations, results further supported by analysis of CAR target gene expression in primary human hepatocytes. In addition, comparative genomic analyses show that the typical mouse, rat, and marmoset models of DEHP toxicity cannot accurately profile potential human toxicity because of these species' inability to generate a CAR2-like transcript. The discovery that CAR2 is an ultimate human DEHP receptor identifies a novel pathway modulating human DEHP toxicity with potential clinical implications for a subset of patients undergoing critical care medical interventions. C1 [DeKeyser, Joshua G.; Prabhu, K. Sandeep; Omiecinski, Curtis J.] Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Stagliano, Michael C.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA. [Stagliano, Michael C.; Jones, A. Daniel] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Jones, A. Daniel] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Auerbach, Scott S.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Omiecinski, CJ (reprint author), Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. EM cjo10@psu.edu RI Jones, Arthur/C-2670-2013 OI Jones, Arthur/0000-0002-7408-6690 FU National Institutes of Health National Institute of General Medical Sciences [GM66411]; National Institutes of Health National Institute of Environmental Health Sciences; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [N01-DK-7-0004/HHSN267200700004c]; National Science Foundation [DBI-0619489] FX This work was supported, in part, by the National Institutes of Health National Institute of General Medical Sciences [Grant GM66411]; by the Intramural Research program of the National Institutes of Health National Institute of Environmental Health Sciences; and by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Contract N01-DK-7-0004/HHSN267200700004c]. The Quattro Premier XE mass spectrometer was purchased with funds from the National Science Foundation [Grant DBI-0619489]. NR 37 TC 40 Z9 42 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 2009 VL 75 IS 5 BP 1005 EP 1013 DI 10.1124/mol.108.053702 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 436VS UT WOS:000265444800001 PM 19211671 ER PT J AU Schulze, TG Detera-Wadleigh, SD Akula, N Gupta, A Kassem, L Steele, J Pearl, J Strohmaier, J Breuer, R Schwarz, M Propping, P Nothen, MM Cichon, S Schumacher, J Rietschel, M McMachon, FJ AF Schulze, T. G. Detera-Wadleigh, S. D. Akula, N. Gupta, A. Kassem, L. Steele, J. Pearl, J. Strohmaier, J. Breuer, R. Schwarz, M. Propping, P. Noethen, M. M. Cichon, S. Schumacher, J. Rietschel, M. McMachon, F. J. CA NIMH Genetics Initiative Bipolar D TI Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE genome-wide association study; allelic heterogeneity; interaction; ankyrins; linkage disequilibrium; manic depressive illness ID GENOME-WIDE ASSOCIATION; CHANNELS; AXON AB Two recent reports have highlighted ANK3 as a susceptibility gene for bipolar disorder (BD). We first reported association between BD and the ANK3 marker rs9804190 in a genome-wide association study (GWAS) of two independent samples (Baum et al., 2008). Subsequently, a meta-analysis of GWAS data based on samples from the US and the UK reported association with a different ANK3 marker, rs10994336 (Ferreira et al., 2008). The markers lie about 340 kb apart in the gene. Here, we test both markers in additional samples and characterize the contribution of each marker to BD risk. Our previously reported findings at rs9804190, which had been based on DNA pooling, were confirmed by individual genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P = 0.05; odds ratio (OR) = 1.24) and German (P = 0.0006; OR = 1.34) samples. This association was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212 controls; P = 0.017; OR = 1.38). A random-effects meta-analysis of all three samples was significant (P = 3 x 10(-6); OR = 1.32), with no heterogeneity. Individual genotyping of rs10994336 revealed a significant association in the German sample (P = 0.0001; OR = 1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were not significant at the P < 0.05 level. Meta-analysis of all three samples supported an association with rs10994336 (P = 1.7 x 10(-5); OR = 1.54), again with no heterogeneity. There was little linkage disequilibrium between the two markers. Further analysis suggested that each marker contributed independently to BD, with no significant marker x marker interaction. Our findings strongly support ANK3 as a BD susceptibility gene and suggest true allelic heterogeneity. C1 [Schulze, T. G.; Detera-Wadleigh, S. D.; Akula, N.; Gupta, A.; Kassem, L.; Steele, J.; Pearl, J.; Schumacher, J.; McMachon, F. J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Schulze, T. G.; Strohmaier, J.; Breuer, R.; Rietschel, M.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schwarz, M.] Psychiat Zentrum Norbaden, Wiesloch, Germany. [Propping, P.; Noethen, M. M.; Cichon, S.; Schumacher, J.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Noethen, M. M.; Cichon, S.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany. [Rietschel, M.] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. RP Schulze, TG (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept HHS, Bldg 35,Room 1A205,35 Convent Dr, Bethesda, MD 20892 USA. EM schulzet@mail.nih.gov RI Schulze, Thomas/H-2157-2013; Schumacher, Johannes/F-4970-2015; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014 OI Schumacher, Johannes/0000-0001-9217-6457; McMahon, Francis/0000-0002-9469-305X; Nothen, Markus/0000-0002-8770-2464; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X FU NIMH Intramural Research Program; Deutsche Forschungsgemeinschaft; National German Genome Research Network of the Federal Ministry of Education and Research; National Alliance for Research on Schizophrenia and Depression; Alfried Krupp von Bohlen und Halbach-Stiftung FX The investigators and coinvestigators are: ENH/Northwestern University, Evanston, IL, MH059571-Pablo V Gejman, MD (Collaboration Coordinator; PI), Alan R Sanders, MD; Emory University School of Medicine, Atlanta, GA, MH59587-Farooq Amin, MD (PI); Louisiana State University Health Sciences Center; New Orleans, LA, MH067257-Nancy Buccola APRN, BC, MSN (PI); University of California-Irvine, Irvine, CA, MH60870-William Byerley, MD (PI); Washington University, St Louis, MO, U01, MH060879-C Robert Cloninger, MD (PI); University of Iowa, Iowa, IA, MH59566-Raymond Crowe, MD (PI), Donald Black, MD; University of Coloado, Denver, CO, MH059565-Robert Freedman, MD (PI); University of Pennsylvania, Philadelphia, PA, MH061675-Douglas Levinson, MD (PI); University of Queensland, QLD, Australia, MH059588-Bryan Mowry, MD (PI); Mt Sinai School of Medicine, New York, NY, MH59586-Jeremy Silverman, PhD (PI). We thank the following clinician colleagues for help in collecting German patients: Margot Albus, Margitta Borrmann-Hassenbach, Ernst Franzek, Jurgen Fritze, Magdalena Gross, Thilo Held, Roland Kreiner, Mario Lanczik, Dirk Lichtermann, Wolfgang Maier, Jurgen Minges, Stephanie Ohlraun, Ulrike Reuner, Monja Tullius, Bettina Weigelt. We thank Jay Tischfield and Douglas Fugman of the Rutgers Cell and DNA Repository for banking blood samples and providing DNA for the NIMH collections. NR 11 TC 89 Z9 91 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2009 VL 14 IS 5 BP 487 EP 491 DI 10.1038/mp.2008.134 PG 5 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 437DS UT WOS:000265467000004 PM 19088739 ER PT J AU Acosta, A Aslanidi, G Geguchadze, R Wright, A Campbell-Thompson, M Baum, BJ Voutetakis, A Devine, DP Zolotukhin, S AF Acosta, Andres Aslanidi, George Geguchadze, Ramaz Wright, Amy Campbell-Thompson, Martha Baum, Bruce J. Voutetakis, Antonis Devine, Darragh P. Zolotukhin, Sergei TI Modulation of Long-Term Feeding Behavior and Social Interactions Using Non-Invasive Gene Therapy with Recombinant AAV Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Acosta, Andres; Aslanidi, George; Geguchadze, Ramaz; Wright, Amy; Campbell-Thompson, Martha; Devine, Darragh P.; Zolotukhin, Sergei] Univ Florida, Gainesville, FL USA. [Baum, Bruce J.; Voutetakis, Antonis] NIDCR, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 169 BP S67 EP S67 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800170 ER PT J AU Agbandje-McKenna, M Govindasamy, L Nam, HJ Gurda, B Ng, R McKenna, R Zolotukhin, S Muzyczka, N Olson, N Baker, T Chiorini, JA Kozyreva, O Samulski, RJ AF Agbandje-McKenna, Mavis Govindasamy, Lakshmanan Nam, Hyun-Joo Gurda, Brittney Ng, Robert McKenna, Robert Zolotukhin, Sergei Muzyczka, Nicholas Olson, Norm Baker, Timothy Chiorini, John A. Kozyreva, Olga Samulski, R. Jude TI Structural Studies of Adeno-Associated Virus Serotypes towards Improved Gene Therapy Applications SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Agbandje-McKenna, Mavis; Govindasamy, Lakshmanan; Nam, Hyun-Joo; Gurda, Brittney; Ng, Robert; McKenna, Robert; Zolotukhin, Sergei; Muzyczka, Nicholas] Univ Florida, Gainesville, FL USA. [Olson, Norm; Baker, Timothy] Univ Calif San Diego, San Diego, CA 92103 USA. [Chiorini, John A.] NIDCR, GTTB, NIH, Bethesda, MD USA. [Kozyreva, Olga; Samulski, R. Jude] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 370 BP S144 EP S145 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800369 ER PT J AU Bauer, TR Olson, EM Allen, JM Tuschong, LM Burkholder, TH Russell, DW Hickstein, DD AF Bauer, Thomas R., Jr. Olson, Erik M. Allen, James M. Tuschong, Laura M. Burkholder, Tanya H. Russell, David W. Hickstein, Dennis D. TI Foamy Viral Vectors with an Internal Mouse Pgk Promoter Lead to Very Low Levels of CD18+Leukocytes In Vivo in Canine Leukocyte Adhesion Deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Bauer, Thomas R., Jr.; Tuschong, Laura M.; Hickstein, Dennis D.] Natl Canc Inst, Natl Inst Hlth, Experimental Transplantat & Immunol Branch, Bethesda, MD USA. [Olson, Erik M.; Allen, James M.; Russell, David W.] Univ Washington, Dept Hematol, Seattle, WA 98195 USA. [Burkholder, Tanya H.] Natl Inst Hlth, Div Vet Serv, Off Res Serv, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S377 EP S377 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801561 ER PT J AU Burnight, ER Staber, J Sarvida, ME Xie, LT Kaminski, JM McCray, PB AF Burnight, Erin R. Staber, Janice Sarvida, Marie-Ellen Xie, Litao Kaminski, Joseph M. McCray, Paul B., Jr. TI Gene Transfer to Murine Liver Using a piggyBAC Transposon System SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Burnight, Erin R.; Staber, Janice; Xie, Litao; McCray, Paul B., Jr.] Univ Iowa, Iowa City, IA USA. [Sarvida, Marie-Ellen] Loyola Univ, Chicago, IL 60611 USA. [Kaminski, Joseph M.] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S283 EP S284 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801316 ER PT J AU Cecchini, S Virag, T Negrete, A Kotin, RM AF Cecchini, Sylvain Virag, Tamas Negrete, Alejandro Kotin, Robert M. TI Production and Processing of rAAV-U7smOPT in 100 L Bioreactors for Canine Models of Duchenne Muscular Dystrophy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Cecchini, Sylvain; Virag, Tamas; Negrete, Alejandro; Kotin, Robert M.] NHLBI, NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. [Negrete, Alejandro] NIDDK, Biotechnol Unit, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 42 BP S17 EP S17 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800043 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI Rescue of a Lethal Murine Model of Methylmalonic Acidemia Using rAAV8 Mediated Gene Therapy - One Year Post-Treatment SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 28 BP S11 EP S12 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800029 ER PT J AU Chiorini, JA Weller, ML Amornphimoltham, P Schmidt, M Gutkind, JS AF Chiorini, John A. Weller, Melodie L. Amornphimoltham, Panomwat Schmidt, Michael Gutkind, J. Silvio TI Epidermal Growth Factor Receptor Is a Receptor for Adeno-Associated Virus Serotype 6 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Chiorini, John A.; Weller, Melodie L.; Schmidt, Michael] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. [Amornphimoltham, Panomwat; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 374 BP S146 EP S146 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800373 ER PT J AU Chung, DC Cheng, D Oh, E Swaroop, A Bennett, J AF Chung, Daniel C. Cheng, Debbie Oh, Edwin Swaroop, Anand Bennett, Jean TI Neonatal Gene Delivery to Nrl-/-Mouse Photoreceptors Restores Rhodopsin Expression SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Chung, Daniel C.; Cheng, Debbie; Bennett, Jean] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. [Oh, Edwin; Swaroop, Anand] Univ Michigan, Ann Arbor, MI 48109 USA. [Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S197 EP S197 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801088 ER PT J AU Correia, C Weinstein, D Fiske, L Verstegen, J Specht, A Struck, M Ramirez, H Onclin-Verstegen, K Porvasnik, S Chou, J Byrne, B Mah, C AF Correia, Catherine Weinstein, David Fiske, Laurie Verstegen, John Specht, Andrew Struck, Maggie Ramirez, Harvey Onclin-Verstegen, Karine Porvasnik, Stacy Chou, Janice Byrne, Barry Mah, Cathryn TI Administration of rAAV2/8 and rAAV2/1 Vectors Mediates Sustained Correction of a Canine Model of Glycogen Storage Disease Type Ia SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Verstegen, John; Onclin-Verstegen, Karine] Univ Florida, LACS, Gainesville, FL USA. [Specht, Andrew] Univ Florida, SACS, Gainesville, FL USA. [Struck, Maggie; Ramirez, Harvey] Univ Florida, ACS, Gainesville, FL USA. [Chou, Janice] NICHD, NIH, Sect Cellular Differentiat, Bethesda, MD USA. [Byrne, Barry; Mah, Cathryn] Univ Florida, Powell Gene Therapy Ctr, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 168 BP S66 EP S66 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800169 ER PT J AU Di Pasquale, G Ostedgaard, LS Welsh, MJ Chiorini, JA AF Di Pasquale, Giovanni Ostedgaard, Lynda S. Welsh, Michael J. Chiorini, John A. TI BAAV Mediated Transduction of Lung Epithelia In Vitro and In Vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Di Pasquale, Giovanni; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, NIH, Mol Physiol & Therapeut Branch, Bethesda, MD USA. [Ostedgaard, Lynda S.; Welsh, Michael J.] Univ Iowa, Roy J & Lucille Carver Coll Med, Howard Hughes Med Inst, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S320 EP S320 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801409 ER PT J AU Donsante, A Tang, JR Brinster, LR Holmes, CS Goldstein, DS Centeno, JA Kaler, SG AF Donsante, Anthony Tang, Jingrong Brinster, Lauren R. Holmes, Courtney S. Goldstein, David S. Centeno, Jose A. Kaler, Stephen G. TI Combined Brain-Directed Recombinant Adeno-Associated Virus Gene Therapy and Copper Rescues a Murine Model of Severe Menkes Disease SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Donsante, Anthony; Tang, Jingrong; Kaler, Stephen G.] NICHD, Unit Ped Genet, Program Mol Med, NIH, Bethesda, MD USA. [Brinster, Lauren R.] NIH, Div Vet Res, Bethesda, MD 20892 USA. [Holmes, Courtney S.; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Centeno, Jose A.] Armed Forces Inst Pathol, Div Biophys Tox, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 384 BP S150 EP S150 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800383 ER PT J AU Downey, SG Johnson, LA Morgan, RA Cohen, CJ Zheng, ZL Rosenberg, SA Feldman, SA AF Downey, Stephanie G. Johnson, Laura A. Morgan, Richard A. Cohen, Cyrille J. Zheng, Zhili Rosenberg, Steven A. Feldman, Steven A. TI Substitution of a Murine Constant Region Enhances Effector Function of a Melanoma Specific Human T-Cell Receptor SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Downey, Stephanie G.; Johnson, Laura A.; Morgan, Richard A.; Zheng, Zhili; Rosenberg, Steven A.; Feldman, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Cohen, Cyrille J.] Bar Ilan Univ, Lab Tumor Immunol & Immunotherapy, Ramat Gan, Israel. RI Johnson, Laura/H-4861-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S307 EP S307 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801373 ER PT J AU Fowler, CJ Hunter, MJ Nelson, EJR Tuschong, LM Bauer, TR Hickstein, DD AF Fowler, Cedar J. Hunter, Michael J. Nelson, Everette J. R. Tuschong, Laura M. Bauer, Thomas R., Jr. Hickstein, Dennis D. TI Lentiviral Vectors with Leukocyte Integrin CD11b Promoter Leads to Efficient Transduction of Canine Leukocyte Adhesion Deficiency CD34+Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Fowler, Cedar J.; Hunter, Michael J.; Nelson, Everette J. R.; Tuschong, Laura M.; Bauer, Thomas R., Jr.; Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. [Fowler, Cedar J.] HHMI, NIH, Res Scholars Program, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 79 BP S32 EP S32 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800080 ER PT J AU Ghosh, A Wang, CW Elkahloun, AG Silvin, C Candotti, F AF Ghosh, Amrita Wang, Chenwei Elkahloun, Abdel G. Silvin, Chris Candotti, Fabio TI Effects of Culture Conditions and Viral Envelope on Gene Expression Profile and Retroviral Vector Integration in Human Hematopoietic CD34+Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Ghosh, Amrita; Wang, Chenwei; Elkahloun, Abdel G.; Silvin, Chris; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S252 EP S252 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801233 ER PT J AU Greene, MR Throm, RE Lockey, T Sorrentino, BP De Ravin, SS Malech, HL Gray, JT AF Greene, Michael R. Throm, Robert E. Lockey, Timothy Sorrentino, Brian P. De Ravin, Suk See Malech, Harry L. Gray, John T. TI Efficient Transduction of Human CD34+Cells with an Insulated SIN Lentiviral Vector for SCID-X1 Produced from a Stable Producer Cell Line SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Greene, Michael R.; Throm, Robert E.; Lockey, Timothy; Sorrentino, Brian P.; Gray, John T.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [De Ravin, Suk See; Malech, Harry L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 309 BP S120 EP S120 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800308 ER PT J AU Gurda, BL DiMattia, MA Miller, EB Bennett, A McKenna, R Zolotukhin, S Chen, W Muzyczka, N Weichert, W Nelson, C Chiorini, JA Olson, N Baker, T Parrish, CR Agbandje-McKenna, M AF Gurda, Brittney L. DiMattia, Micheal A. Miller, Edward B. Bennett, Antonette McKenna, Robert Zolotukhin, Sergei Chen, Weijun Muzyczka, Nicholas Weichert, Wendy Nelson, Christian Chiorini, John A. Olson, Norm Baker, Tim Parrish, Colin R. Agbandje-McKenna, Mavis TI Towards Characterizing Vector-Host Interactions: Adeno-Associated Virus Capsids in Complex with Antibody Fragments SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Zolotukhin, Sergei] Univ Florida, Div Cellular & Mol Therapy, Gainesville, FL USA. [Weichert, Wendy; Nelson, Christian; Parrish, Colin R.] Cornell Univ, Ithaca, NY USA. [Chiorini, John A.] NIDCR, Natl Inst Hlth, Bethesda, MD USA. [Olson, Norm; Baker, Tim] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S295 EP S295 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801345 ER PT J AU Holczbauer, A Kachapati, K Arya, S AF Holczbauer, Agnes Kachapati, Kritika Arya, Suresh TI Designing Trans-Regulated Lentiviral Vectors for Gene Transfer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Holczbauer, Agnes] Natl Canc Inst, Lab Cellular Carcinogenesis, Bethesda, MD USA. [Kachapati, Kritika; Arya, Suresh] Natl Canc Inst, Basic Res Lab, Bethesda, MD USA. [Arya, Suresh] Natl Canc Inst, Dev Therapeut Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S173 EP S173 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801017 ER PT J AU Huang, X Guo, HF Tammana, S Wong, M Mellgren, E Bassi, P Jung, YC Ekker, S Wu, XL Wang, SM Zhou, XZ AF Huang, Xin Guo, Hongfeng Tammana, Syam Wong, Marianna Mellgren, Emil Bassi, Preetinder Jung, Yong-Chul Ekker, Stephen Wu, Xiaolin Wang, San Ming Zhou, Xianzheng TI Genome-Wide Analysis of Sleeping Beauty (SB), piggyBac and Tol2 Transposon Mediated Integration in Human Primary T Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Bassi, Preetinder] Univ Minnesota, Coll Biol Sci, Minneapolis, MN USA. [Mellgren, Emil] Macalester Coll, St Paul, MN 55105 USA. [Jung, Yong-Chul; Wang, San Ming] Northwestern Univ, Ctr Funct Genom, Evanston, IL USA. [Ekker, Stephen] Mayo Clin, Rochester, MN USA. [Wu, Xiaolin] NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S329 EP S330 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801436 ER PT J AU Hunter, MJ Tuschong, LM Fowler, CJ Nelson, EJR Burkholder, TH Bauer, TR Hickstein, DD AF Hunter, Michael J. Tuschong, Laura M. Fowler, Cedar J. Nelson, Everette J. R. Burkholder, Tanya H. Bauer, Thomas R., Jr. Hickstein, Dennis D. TI Treatment of Canine Leukocyte Adhesion Deficiency Using a SIN Lentiviral Vector and Human CD18 Promoter Expressing Canine CD18 SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Hunter, Michael J.; Tuschong, Laura M.; Nelson, Everette J. R.; Bauer, Thomas R., Jr.; Hickstein, Dennis D.] NCI, Bethesda, MD 20892 USA. [Fowler, Cedar J.] Howard Hughes Med Inst, HHMI, NIH, Res Scholars Program, Chevy Chase, MD USA. [Burkholder, Tanya H.] NIH, Dept Vet Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 416 BP S163 EP S163 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800415 ER PT J AU Iida, Y Ohzeki, J Kazuki, Y Hoshiya, H Takiguchi, M Hayashi, M Nakano, M Masumoto, H Earnshaw, WC Larionov, V Oshimura, M AF Iida, Yuichi Ohzeki, Jun-ichirou Kazuki, Yasuhiro Hoshiya, Hidetoshi Takiguchi, Masato Hayashi, Masahiro Nakano, Megumi Masumoto, Hiroshi Earnshaw, William C. Larionov, Vladimir Oshimura, Mitsuo TI Towards the Extension of Life-Span of a Human Somatic Stem Cells Using a Human Artificial Chromosome Carrying a Conditional Centromere SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Iida, Yuichi; Kazuki, Yasuhiro; Hoshiya, Hidetoshi; Takiguchi, Masato; Hayashi, Masahiro; Oshimura, Mitsuo] Tottori Univ, Grad Sch Med Sci, Yonago, Tottori, Japan. [Ohzeki, Jun-ichirou; Masumoto, Hiroshi] Kazusa DNA Res Inst, Lab Cell Engn, Kisarazu, Chiba, Japan. [Nakano, Megumi; Larionov, Vladimir] Natl Canc Ctr, Lab Biosyst & Canc, NIH, Bethesda, WA USA. [Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S274 EP S274 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801292 ER PT J AU Karne, NK Yang, S Downey, SG Rosenberg, SA Morgan, RA Feldman, SA AF Karne, Neel K. Yang, Scicheng Downey, Stephanie G. Rosenberg, Steven A. Morgan, Richard A. Feldman, Steven A. TI Optimization of Lentiviral Transduction of Human Peripheral Blood Lymphocytes for TCR Adoptive Cell Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Karne, Neel K.; Yang, Scicheng; Downey, Stephanie G.; Rosenberg, Steven A.; Morgan, Richard A.; Feldman, Steven A.] NCI, NIH, Dept Surg, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 83 BP S34 EP S34 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800084 ER PT J AU Kwilas, AR Yednak, MA Zhang, LQ Collins, PL Pickles, RJ Peeples, ME AF Kwilas, Anna R. Yednak, Mark A. Zhang, Liquin Collins, Peter L. Pickles, Raymond J. Peeples, Mark E. TI Respiratory Syncytial Virus Based Gene Therapy Vectors for the Treatment of Cystic Fibrosis SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Kwilas, Anna R.] Ohio State Univ, Integrated Biomed Sci Grad Program, Columbus, OH 43210 USA. [Peeples, Mark E.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Kwilas, Anna R.; Yednak, Mark A.; Peeples, Mark E.] Nationwide Childrens Hosp, Ctr Vaccines & Immun, Res Inst, Columbus, OH USA. [Zhang, Liquin; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC USA. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S312 EP S312 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801387 ER PT J AU Li, L Kotin, R AF Li, Lina Kotin, Robert TI High-Yield AAV Production Clonal SF9/ITR-GFP Stable Cell Lines Obtained from Spodoptera frugiperda Sf9 Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Li, Lina; Kotin, Robert] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S272 EP S272 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801286 ER PT J AU Machen, L Zourelias, L Zheng, CY MacDougall, MJ Passineau, MJ AF Machen, Laurie Zourelias, Lee Zheng, Changyu MacDougall, Mary J. Passineau, Michael J. TI Endocrine Secretion of alpha-Galactosidase A Following Adenovrius-Mediated Gene Transfer to the Salivary Gland SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Machen, Laurie; Zourelias, Lee; Passineau, Michael J.] Allegheny Singer Res Inst, Pittsburgh, PA 15212 USA. [Zheng, Changyu] NIDCR, Gene Therapy & Therapeut Branch, Bethesda, MD USA. [MacDougall, Mary J.] Univ Alabama, Inst Oral Hlth Res, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S344 EP S344 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801474 ER PT J AU Muul, LM Jagadeesh, J Carbonaro, DA Sokolic, R Kesserwan, C Garabedian, E Silvin, C Shaw, K Choi, C Davis, CM Kohn, DB Candotti, F AF Muul, Linda M. Jagadeesh, Jayashree Carbonaro, Denise A. Sokolic, Robert Kesserwan, Chimene Garabedian, Elizabeth Silvin, Christopher Shaw, Kit Choi, Christopher Davis, Carla M. Kohn, Donald B. Candotti, Fabio TI Comparison of In Vivo Expression of Two Adenosine Deaminase (ADA) Retroviral Vectors in Patients Receiving ADA Gene Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Muul, Linda M.; Jagadeesh, Jayashree; Sokolic, Robert; Kesserwan, Chimene; Garabedian, Elizabeth; Silvin, Christopher; Candotti, Fabio] NHGRI, GMBB, NIH, Bethesda, MD 20892 USA. [Carbonaro, Denise A.; Shaw, Kit; Choi, Christopher; Kohn, Donald B.] Univ Calif Los Angeles, Los Angeles, CA USA. [Carbonaro, Denise A.; Shaw, Kit; Choi, Christopher; Kohn, Donald B.] MIMG, Los Angeles, CA USA. [Davis, Carla M.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S373 EP S373 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801550 ER PT J AU Nelson, EJR Hunter, MJ Tuschong, LM Fowler, CJ Bauer, TR Hickstein, DD AF Nelson, Everette J. R. Hunter, Michael J. Tuschong, Laura M. Fowler, Cedar J. Bauer, Thomas R., Jr. Hickstein, Dennis D. TI Lentiviral Vectors Containing Internal Cellular Promoters Fail To Express Therapeutic Levels of CD18 in Canine Leukocyte Adhesion Deficiency SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Nelson, Everette J. R.; Hunter, Michael J.; Tuschong, Laura M.; Bauer, Thomas R., Jr.; Hickstein, Dennis D.] Natl Canc Inst, Bethesda, MD USA. [Fowler, Cedar J.] Howard Hughes Med Insitute, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 306 BP S119 EP S119 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800305 ER PT J AU Patel, A Gray, M Taylor, T Tran, KN Feldmann, H Kobasa, D Kobinger, GP AF Patel, Ami Gray, Michael Taylor, Tracy Tran, Kaylie N. Feldmann, Heinz Kobasa, Darwyn Kobinger, Gary P. TI Evaluation of Different Combinations of DNA Vaccines Expressing H5N1 Antigens Following Lethal Challenge with Homologous and Heterologous Avian Influenza Isolates SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Patel, Ami; Gray, Michael; Taylor, Tracy; Tran, Kaylie N.; Kobasa, Darwyn; Kobinger, Gary P.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada. [Patel, Ami; Kobasa, Darwyn; Kobinger, Gary P.] Univ Manitoba, Winnipeg, MB, Canada. [Feldmann, Heinz] NIAID, Rocky Mt Labs, Virol Lab, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S370 EP S371 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801543 ER PT J AU Porada, CD Sanada, C Wood, JA Lozier, JN Long, C Westhusin, M Kraemer, D Almeida-Porada, G AF Porada, Christopher D. Sanada, Chad Wood, Josh A. Lozier, Jay N. Long, Charles Westhusin, Mark Kraemer, Duane Almeida-Porada, Graca TI Creation and Characterization of a New Large Animal Model for Hemophilia A Gene Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Porada, Christopher D.; Sanada, Chad; Wood, Josh A.; Almeida-Porada, Graca] Univ Nevada, Reno, NV 89557 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. [Lozier, Jay N.] Texas A&M Univ, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S238 EP S238 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801198 ER PT J AU Sahib, MM Nepomuceno, R Tran, KN Flick, R Feldmann, H Kobinger, GP AF Sahib, Mickey M. Nepomuceno, Roman Tran, Kaylie N. Flick, Ramon Feldmann, Heinz Kobinger, Gary P. TI Rapid Development of Adenovirus-Based Vaccines Against Emerging/Re-Emerging Biosafety Level 4 Viruses SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Sahib, Mickey M.; Nepomuceno, Roman; Tran, Kaylie N.; Kobinger, Gary P.] Natl Microbiol Lab, Winnipeg, MB, Canada. [Sahib, Mickey M.; Kobinger, Gary P.] Univ Manitoba, Winnipeg, MB, Canada. [Flick, Ramon] Bioprotection Syst Corp, Ames, IA USA. [Feldmann, Heinz] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 118 BP S46 EP S46 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800119 ER PT J AU Sanchez-Bonilla, M Qiu, SB Black, ME AF Sanchez-Bonilla, Marilyn Qiu, Songbo Black, Margaret E. TI Evaluation of Mutant Bacterial Cytosine Deaminase and Thymidine Kinase Fusions in Double Suicide Gene Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Sanchez-Bonilla, Marilyn; Black, Margaret E.] Washington State Univ, Pharmacol & Toxicol Grad Program, Pullman, WA 99164 USA. [Sanchez-Bonilla, Marilyn; Qiu, Songbo; Black, Margaret E.] Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA. [Sanchez-Bonilla, Marilyn; Black, Margaret E.] Washington State Univ, NIH, Biotechnol Training Program, Pullman, WA 99164 USA. RI Black, Margaret/I-2957-2015 OI Black, Margaret/0000-0002-3152-5112 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S222 EP S222 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801158 ER PT J AU Serwylo, O Wong, G Tran, K Kobasa, D Ebihara, H Feldmann, H Kobinger, GP AF Serwylo, Olena Wong, Gary Tran, Kaylie Kobasa, Darwyn Ebihara, Hideki Feldmann, Heinz Kobinger, Gary P. TI Development of a Recombinant Vesicular Stomatitis Virus Vector Capable of Expressing Four Antigens for Vaccine Applications SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Serwylo, Olena; Wong, Gary; Tran, Kaylie; Kobasa, Darwyn; Kobinger, Gary P.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Wong, Gary; Kobinger, Gary P.] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Kobasa, Darwyn] Publ Hlth Agcy Canada, Natl Microbiol Lab, Resp Viruses Viral Dis Div, Winnipeg, MB, Canada. [Ebihara, Hideki; Feldmann, Heinz] NIAID, Virol Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S307 EP S308 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801375 ER PT J AU Shaw, KL Sokolic, R Choi, C Muul, L Smogorzewska, M Jagadeesh, J Garabedian, E Kesserwan, C Carbonaro-Sarracino, DA Hershfield, MS Wayne, A Shah, A Kapoor, N Candotti, F Kohn, DB AF Shaw, Kit L. Sokolic, Robert Choi, Christopher Muul, Linda Smogorzewska, Monika Jagadeesh, Jayashree Garabedian, Elizabeth Kesserwan, Chimene Carbonaro-Sarracino, Denise A. Hershfield, Michael S. Wayne, Alan Shah, Ami Kapoor, Neena Candotti, Fabio Kohn, Donald B. TI Immune Reconstitution after Gene Therapy for Adenosine Deaminase Deficient Severe Combined Immune Deficiency (ADA-SCID) SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Shaw, Kit L.; Choi, Christopher; Smogorzewska, Monika; Carbonaro-Sarracino, Denise A.; Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol, Los Angeles, CA USA. [Shaw, Kit L.; Choi, Christopher; Smogorzewska, Monika; Carbonaro-Sarracino, Denise A.; Kohn, Donald B.] Univ Calif Los Angeles, Dept Mol Genet & Pediat, Los Angeles, CA USA. [Sokolic, Robert; Muul, Linda; Jagadeesh, Jayashree; Garabedian, Elizabeth; Kesserwan, Chimene; Wayne, Alan; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. [Hershfield, Michael S.] Duke Univ, Durham, NC USA. [Shah, Ami; Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 355 BP S138 EP S138 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800354 ER PT J AU Smith, RH Levy, JR Kotin, RM AF Smith, Richard H. Levy, Justin R. Kotin, Robert M. TI A Simplified System for Baculovirus-Mediated Production of rAAV Particles in Insect Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Smith, Richard H.; Levy, Justin R.; Kotin, Robert M.] NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 103 BP S41 EP S41 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800104 ER PT J AU Steel, JC Ramlogan, CA Yu, P Waldmann, TA Morris, JC AF Steel, Jason C. Ramlogan, Charmaine A. Yu, Ping Waldmann, Thomas A. Morris, John C. TI Adenoviral Mediated IL-15 and IL-15R alpha Immunotherapy of a Murine Breast Cancer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Steel, Jason C.; Ramlogan, Charmaine A.; Yu, Ping; Waldmann, Thomas A.; Morris, John C.] NCI, Metab Branch, Bethesda, MD 20892 USA. RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 399 BP S156 EP S156 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800398 ER PT J AU Throm, RE Ouma, AA Chandrasekaran, A Lockey, T Greene, M Zhou, S Persons, DA Malech, H Sorrentino, BP Gray, JT AF Throm, Robert E. Ouma, Annastasia A. Chandrasekaran, Anantharaman Lockey, Timothy Greene, Michael Zhou, Sheng Persons, Derek A. Malech, Harry Sorrentino, Brian P. Gray, John T. TI Efficient Construction of Producer Cell Lines for SIN, Clinical Lentiviral Vectors by Concatemer Array Transfection SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Throm, Robert E.; Ouma, Annastasia A.; Chandrasekaran, Anantharaman; Lockey, Timothy; Greene, Michael; Zhou, Sheng; Persons, Derek A.; Sorrentino, Brian P.; Gray, John T.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Malech, Harry] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 44 BP S18 EP S18 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800045 ER PT J AU Uchida, N Washington, K Hsieh, MM Bonifacino, AC Krouse, AE Metzger, ME Donahue, RE Tisdale, JF AF Uchida, Naoya Washington, Kareem Hsieh, Matthew M. Bonifacino, Aylin C. Krouse, Allen E. Metzger, Mark E. Donahue, Robert E. Tisdale, John F. TI Development of Rhesus Hematopoietic Stem Cell Gene Therapy Model Using HIV1-Based Lentiviral Vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Uchida, Naoya; Washington, Kareem; Hsieh, Matthew M.; Donahue, Robert E.; Tisdale, John F.] NHLBI, NIH, MCHB, Bethesda, MD 20892 USA. [Bonifacino, Aylin C.; Krouse, Allen E.; Metzger, Mark E.] NHLBI, NIH, HB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 365 BP S142 EP S143 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800364 ER PT J AU Uchiyama, T Shimizu, M Thrasher, AJ Candotti, F AF Uchiyama, Toru Shimizu, Masaki Thrasher, Adrian J. Candotti, Fabio TI Development of Gene Transfer System for Wiskott-Aldrich Syndrome Using Foamy Virus Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Uchiyama, Toru; Shimizu, Masaki; Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Thrasher, Adrian J.] Inst Child Hlth, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S375 EP S376 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801556 ER PT J AU Venditti, CP Manoli, E Chandler, RJ AF Venditti, Charles P. Manoli, Eirini Chandler, Randy J. TI A Method To Determine the In Vivo Oxidative Capacity for 13C Isotopomers in Mice: Use To Study Intermediary Metabolism and To Monitor Transgene Activity SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Venditti, Charles P.; Manoli, Eirini; Chandler, Randy J.] NHGRI, NIH, GMBB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 182 BP S72 EP S72 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800183 ER PT J AU Wu, Z Park, TK Kjellstrom, S Zeng, Y Bush, RA Sieving, PA Colosi, P AF Wu, Zhijian Park, Tae Kwann Kjellstrom, Sten Zeng, Yong Bush, Ronald A. Sieving, Paul A. Colosi, Peter TI Intravitreal Administration of an AAV8 Retinoschisin Vector to the Rs1-KO Mouse Results in Cell Type-Specifi c Gene Expression and Rescue of the Disease Phenotype SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Wu, Zhijian; Colosi, Peter] NEI, Natl Inst Hlth, Ocular Gene Therapy Lab, Rockville, MD USA. [Park, Tae Kwann; Kjellstrom, Sten; Zeng, Yong; Bush, Ronald A.; Sieving, Paul A.] Natl Inst Deafness & Other Commun Disorders, Natl Inst Hlth, Sect Translat Res Retinal & Macular Degenerat, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S288 EP S288 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801327 ER PT J AU Wu, ZJ Yang, HY Colosi, P AF Wu, Zhijian Yang, Hongyan Colosi, Peter TI Packaging of Genomes Greater Than 5 Kb in Length into AAV5 Capsids Is Not Efficient Using a Common Vector Production Protocol SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Wu, Zhijian; Yang, Hongyan; Colosi, Peter] NEI, NIH, Unit Ocular Gene Therapy, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 97 BP S39 EP S39 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800098 ER PT J AU Yang, SC Zheng, ZL Karne, NK Zhang, L Parker, LL Dudley, ME Feldman, SA Rosenberg, SA Morgan, RA AF Yang, Shicheng Zheng, Zhili Karne, Neel K. Zhang, Ling Parker, Linda L. Dudley, Mark E. Feldman, Steven A. Rosenberg, Steven A. Morgan, Richard A. TI Combination of a Safety-Modified Lentiviral Vector and Artificial Antigen Presenting Cell-Mediated Expansion Generate Potent Antitumor CD8 Lymphocytes for TCR Gene Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Yang, Shicheng; Zheng, Zhili; Karne, Neel K.; Zhang, Ling; Parker, Linda L.; Dudley, Mark E.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.] Ctr Canc Res, Surg Branch, NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 64 BP S27 EP S27 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800065 ER PT J AU Zhang, L Yang, SC Zheng, ZL Zhao, YB Inozume, T Kerkar, S Yu, ZY Yang, JC Restifo, NP Rosenberg, SA Morgan, RA AF Zhang, Ling Yang, Shicheng Zheng, Zhili Zhao, Yanbing Inozume, Takashi Kerkar, Sidharth Yu, Zhiya Yang, James C. Restifo, Nicholas P. Rosenberg, Steven A. Morgan, Richard A. TI Improving Adoptive T Cell Therapy Using an NFAT Driven Human Single Chain IL-12 Expression Vector SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Zhang, Ling; Yang, Shicheng; Zheng, Zhili; Zhao, Yanbing; Inozume, Takashi; Kerkar, Sidharth; Yu, Zhiya; Yang, James C.; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NIH, Surg Branch, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 228 BP S89 EP S90 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800229 ER PT J AU Zheng, CY Cotrim, AP Sugito, T Sunshine, AN Liu, L Sowers, A Mitchell, JB Baum, BJ AF Zheng, Changyu Cotrim, Ana P. Sugito, Takayuki Sunshine, Abraham N. Liu, Lina Sowers, Anastasia Mitchell, James B. Baum, Bruce J. TI Prevention of Radiation-Induced Oral Mucositis Following Adenoviral Vector-Mediated Transfer of the Keratinocyte Growth Factor cDNA to Mouse Submandibular Glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Zheng, Changyu; Cotrim, Ana P.; Sunshine, Abraham N.; Liu, Lina; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Sowers, Anastasia; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sugito, Takayuki] Nagoya Univ, Sch Med, Nagoya, Aichi 4648601, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 BP S372 EP S372 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019801547 ER PT J AU Zheng, CY Nikolov, NP Baum, BJ AF Zheng, Changyu Nikolov, Nikolay P. Baum, Bruce J. TI An E1/E3 Deleted Hybrid Adenoretroviral Vector Reduces Immune Reactivity and Increases Transgene Expression after Administration to Rat Submandibular Glands SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Zheng, Changyu; Nikolov, Nikolay P.; Baum, Bruce J.] Natl Inst Dent & Craniofacial Res, NIH, Molecular Physiol & Therapeut Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 125 BP S48 EP S48 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800126 ER PT J AU Zhou, S DeRavin, SS Hauer, J Lu, T Ma, Z Felsburg, PJ Marcotte, J Jensen, A Abina, SHB Gray, JT Cavazzana-Calvo, M Malech, HL Sorrentino, BP AF Zhou, Sheng DeRavin, Suk See Hauer, Julia Lu, Taihe Ma, Zhijun Felsburg, Peter J. Marcotte, Joseph Jensen, Andrew Abina, Salima Hacein-Bey Gray, John T. Cavazzana-Calvo, Marina Malech, Harry L. Sorrentino, Brian P. TI Correction of SCID-X1 in a Canine Transplant Model and in Primary Human Cells from a SCID-X1 Patient Using SIN Lentiviral Vectors Containing Cellular Transcription Control Elements SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 12th Annual Meeting of the American Society of Gene Therapy CY MAY 27-30, 2009 CL San Diego, CA SP Amer Soc Gene Therapy C1 [Zhou, Sheng; Lu, Taihe; Ma, Zhijun; Gray, John T.; Sorrentino, Brian P.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [DeRavin, Suk See; Marcotte, Joseph; Jensen, Andrew; Malech, Harry L.] NIH, Bethesda, MD 20892 USA. [Hauer, Julia; Abina, Salima Hacein-Bey; Cavazzana-Calvo, Marina] Hop Necker Enfants Malad, Paris, France. [Felsburg, Peter J.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2009 VL 17 SU 1 MA 308 BP S120 EP S120 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 600WO UT WOS:000278019800307 ER PT J AU Chung, YW Jeong, D Noh, OJ Park, YH Kang, SI Lee, MG Lee, TH Yim, MB Kim, IY AF Chung, Youn Wook Jeong, Daewon Noh, Ok Jeong Park, Yong Hwan Kang, Soo Im Lee, Min Goo Lee, Tae-Hoon Yim, Moon Bin Kim, Ick Young TI Antioxidative role of selenoprotein W in oxidant-induced mouse embryonic neuronal cell death SO MOLECULES AND CELLS LA English DT Article DE antioxidant; neuronal cells; oxidative stress; selenium; selenoprotein W ID GLUTATHIONE-PEROXIDASE; THIOREDOXIN REDUCTASE; SELENOCYSTEINE INSERTION; MAMMALIAN SELENOPROTEIN; MUSCULAR-DYSTROPHY; EXPRESSION PATTERN; ELONGATION-FACTOR; DIETARY SELENIUM; RAT MUSCLE; BRAIN AB It has been reported that selenoprotein W (SelW) mRNA is highly expressed in the developing central nerve system of rats, and its expression is maintained until the early postnatal stage. We here found that SelW protein significantly increased in mouse brains of postnatal day 8 and 20 relative to embryonic day 15. This was accompanied by increased expression of SOD1 and SOD2. When the expression of SelW in primary cultured cells derived from embryonic cerebral cortex was knocked down with small interfering RNAs (siRNAs), SelW siRNA-transfected neuronal cells were more sensitive to the oxidative stress induced by treatment of H(2)O(2) than control cells. TUNEL assays revealed that H(2)O(2)-induced apoptotic cell death occurred at a higher frequency in the siRNA-transfected cells than in the control cells. Taken together, our findings suggest that SelW plays an important role in protection of neurons from oxidative stress during neuronal development. C1 [Chung, Youn Wook; Noh, Ok Jeong; Park, Yong Hwan; Kang, Soo Im; Lee, Min Goo; Kim, Ick Young] Korea Univ, Sch Life Sci & Biotechnol, Lab Cellular & Mol Biochem, Seoul 136701, South Korea. [Chung, Youn Wook; Yim, Moon Bin] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Jeong, Daewon] Yeungnam Univ, Coll Med, Dept Microbiol, Taegu 705030, South Korea. [Jeong, Daewon] Yeungnam Univ, Coll Med, Aging Associated Dis Res Ctr, Taegu 705030, South Korea. [Lee, Tae-Hoon] Chonnam Natl Univ, Sch Dent, Stage Brain Korea 21 2, Dent Sci Res Inst, Kwangju 500757, South Korea. RP Kim, IY (reprint author), Korea Univ, Sch Life Sci & Biotechnol, Lab Cellular & Mol Biochem, Seoul 136701, South Korea. EM ickkim@korea.ac.kr FU Korean Government (Ministry of Education and Human Resources Development) [KRF-2005-070-C00086]; Korea University FX We thank Dr. P. B. Chock (Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, USA), Dr. W. Sun and Dr. H. Kim (Department of Anatomy, College of Medicine, Korea University, Seoul, Korea), and Dr. J.H. Baik (School of Life Sciences and Biotechnology, Korea University, Seoul, Korea) for helpful discussions. This work was supported by the Korea Research Foundation Grant funded by the Korean Government (Ministry of Education and Human Resources Development) (KRF-2005-070-C00086) and a Korea University Grant. NR 43 TC 24 Z9 24 U1 1 U2 9 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD MAY PY 2009 VL 27 IS 5 BP 609 EP 613 DI 10.1007/s10059-009-0074-3 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 449RZ UT WOS:000266349000015 PM 19466610 ER PT J AU Zeng, SC Xiang, T Pandita, TK Gonzalez-Suarez, I Gonzalo, S Harris, CC Yang, Q AF Zeng, Sicong Xiang, Tao Pandita, Tej K. Gonzalez-Suarez, Ignacio Gonzalo, Susana Harris, Curtis C. Yang, Qin TI Telomere recombination requires the MUS81 endonuclease SO NATURE CELL BIOLOGY LA English DT Article ID HUMAN-CELLS; DNA-DAMAGE; MAMMALIAN TELOMERES; HOLLIDAY JUNCTIONS; RNA INTERFERENCE; NEGATIVE CELLS; IN-VITRO; LOOP; MAINTENANCE; RESOLUTION AB Telomerase-negative cancer cells maintain their telomeres through the alternative lengthening of telomeres (ALT) pathway(1-3). Although a growing body of evidence demonstrates that the ALT mechanism is a post-replicative telomere recombination process, molecular details of this pathway are largely unknown. Here we demonstrate that MUS81, a DNA structure specific recombination endonuclease, has a key role in the maintenance of telomeres in human ALT cells. We find that MUS81 specifically localizes to ALT-associated promyelocytic leukaemia (PML) nuclear bodies (APBs) and associates with telomeric DNA in ALT cells, which is enriched during the G2 phase of the cell cycle. Depletion of MUS81 results in the reduction of ALT-specific telomere recombination and leads to proliferation arrest of ALT cells. In addition, the endonuclease activity of MUS81 is required for recombination-based ALT cell survival, and the interaction of MUS81 with the telomeric repeat-binding factor TRF2 regulates this enzymatic activity, thereby maintaining telomere recombination. Thus, our results suggest that MUS81 is involved in the maintenance of ALT cell survival at least in part by homologous recombination of telomeres. C1 [Zeng, Sicong; Xiang, Tao; Pandita, Tej K.; Gonzalez-Suarez, Ignacio; Gonzalo, Susana; Yang, Qin] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. [Gonzalez-Suarez, Ignacio; Gonzalo, Susana] Washington Univ, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Yang, Q (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4511 Forest Pk, St Louis, MO 63108 USA. EM qyang@wustl.edu FU Concern Foundation; NIH [CA10445/CA123232]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX We thank R. R. Reddel for ALT cells, and C. H. McGowan for wild-type and mutant MUS81 constructs, the MUS81 antibody and Mus81+/+ and Mus81-/- MEFs. We thank I. Hickson and J. Roti Roti for proof-reading. This work is supported in part by grants from Concern Foundation to Q. Y. and NIH CA10445/CA123232 to T. K. P. This research was also supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 33 TC 50 Z9 50 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD MAY PY 2009 VL 11 IS 5 BP 616 EP U387 DI 10.1038/ncb1867 PG 17 WC Cell Biology SC Cell Biology GA 439PR UT WOS:000265640000020 PM 19363487 ER PT J AU Palavalli, LH Prickett, TD Wunderlich, JR Wei, XM Burrell, AS Porter-Gill, P Davis, S Wang, CW Cronin, JC Agrawal, NS Lin, JC Westbroek, W Hoogstraten-Miller, S Molinolo, AA Fetsch, P Filie, AC O'Connell, MP Banister, CE Howard, JD Buckhaults, P Weeraratna, AT Brody, LC Rosenberg, SA Samuels, Y AF Palavalli, Lavanya H. Prickett, Todd D. Wunderlich, John R. Wei, Xiaomu Burrell, Allison S. Porter-Gill, Patricia Davis, Sean Wang, Chenwei Cronin, Julia C. Agrawal, Neena S. Lin, Jimmy C. Westbroek, Wendy Hoogstraten-Miller, Shelley Molinolo, Alfredo A. Fetsch, Patricia Filie, Armando C. O'Connell, Michael P. Banister, Carolyn E. Howard, Jason D. Buckhaults, Phillip Weeraratna, Ashani T. Brody, Lawrence C. Rosenberg, Steven A. Samuels, Yardena TI Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma SO NATURE GENETICS LA English DT Article ID HUMAN BREAST; CANCER; PROGRESSION; METASTASIS AB A mutational analysis of the matrix metalloproteinase (MMP) gene family in human melanoma identified somatic mutations in 23% of melanomas. Five mutations in one of the most commonly mutated genes, MMP8, reduced MMP enzyme activity. Expression of wild-type but not mutant MMP8 in human melanoma cells inhibited growth on soft agar in vitro and tumor formation in vivo, suggesting that wild-type MMP-8 has the ability to inhibit melanoma progression. C1 [Palavalli, Lavanya H.; Prickett, Todd D.; Wei, Xiaomu; Burrell, Allison S.; Porter-Gill, Patricia; Wang, Chenwei; Cronin, Julia C.; Agrawal, Neena S.; Westbroek, Wendy; Hoogstraten-Miller, Shelley; Brody, Lawrence C.; Samuels, Yardena] NHGRI, NIH, Bethesda, MD 20892 USA. [Wunderlich, John R.; Davis, Sean; Fetsch, Patricia; Filie, Armando C.; Rosenberg, Steven A.] NCI, NIH, Bethesda, MD 20892 USA. [Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA. [Molinolo, Alfredo A.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [O'Connell, Michael P.; Weeraratna, Ashani T.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Banister, Carolyn E.; Buckhaults, Phillip] Univ S Carolina, Sch Med, Columbia, SC USA. [Howard, Jason D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Samuels, Y (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM samuelsy@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU National Human Genome Research Institute; National Institute on Aging FX We thank M. Xu, J. Polite, I. Cardenas-Navia, D. Leja and I. Ginty for technical assistance. We thank R. Weinberg (Massachusetts Institute of Technology) for the Mel-STR cells, and W. Gahl (National Institutes of Health) and R. Alani (Johns Hopkins University) for normal melanocyte RNA. We also thank L. Matrisian, P. Meltzer, T. Waldman, G. Merlino, T. Hornyak and T. Bugge for their comments on the manuscript. Funded by the National Human Genome Research Institute and National Institute on Aging. NR 15 TC 82 Z9 84 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2009 VL 41 IS 5 BP 518 EP 520 DI 10.1038/ng.340 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 438SL UT WOS:000265575600010 PM 19330028 ER PT J AU Thomas, G Jacobs, KB Kraft, P Yeager, M Wacholder, S Cox, DG Hankinson, SE Hutchinson, A Wang, Z Yu, K Chatterjee, N Garcia-Closas, M Gonzalez-Bosquet, J Prokunina-Olsson, L Orr, N Willett, WC Colditz, GA Ziegler, RG Berg, CD Buys, SS McCarty, CA Feigelson, HS Calle, EE Thun, MJ Diver, R Prentice, R Jackson, R Kooperberg, C Chlebowski, R Lissowska, J Peplonska, B Brinton, LA Sigurdson, A Doody, M Bhatti, P Alexander, BH Buring, J Lee, IM Vatten, LJ Hveem, K Kumle, M Hayes, RB Tucker, M Gerhard, DS Fraumeni, JF Hoover, RN Chanock, SJ Hunter, DJ AF Thomas, Gilles Jacobs, Kevin B. Kraft, Peter Yeager, Meredith Wacholder, Sholom Cox, David G. Hankinson, Susan E. Hutchinson, Amy Wang, Zhaoming Yu, Kai Chatterjee, Nilanjan Garcia-Closas, Montserrat Gonzalez-Bosquet, Jesus Prokunina-Olsson, Ludmila Orr, Nick Willett, Walter C. Colditz, Graham A. Ziegler, Regina G. Berg, Christine D. Buys, Saundra S. McCarty, Catherine A. Feigelson, Heather Spencer Calle, Eugenia E. Thun, Michael J. Diver, Ryan Prentice, Ross Jackson, Rebecca Kooperberg, Charles Chlebowski, Rowan Lissowska, Jolanta Peplonska, Beata Brinton, Louise A. Sigurdson, Alice Doody, Michele Bhatti, Parveen Alexander, Bruce H. Buring, Julie Lee, I-Min Vatten, Lars J. Hveem, Kristian Kumle, Merethe Hayes, Richard B. Tucker, Margaret Gerhard, Daniela S. Fraumeni, Joseph F., Jr. Hoover, Robert N. Chanock, Stephen J. Hunter, David J. TI A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) SO NATURE GENETICS LA English DT Article ID SUSCEPTIBILITY GENE; CONFER SUSCEPTIBILITY; COMMON VARIANTS; MUTATIONS; BRCA2; LOCI AB We conducted a three-stage genome-wide association study (GWAS) of breast cancer in 9,770 cases and 10,799 controls in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. In stage 1, we genotyped 528,173 SNPs in 1,145 cases of invasive breast cancer and 1,142 controls. In stage 2, we analyzed 24,909 top SNPs in 4,547 cases and 4,434 controls. In stage 3, we investigated 21 loci in 4,078 cases and 5,223 controls. Two new loci achieved genome-wide significance. A pericentromeric SNP on chromosome 1p11.2 (rs11249433; P = 6.74 x 10(-10) adjusted genotype test, 2 degrees of freedom) resides in a large linkage disequilibrium block neighboring NOTCH2 and FCGR1B; this signal was stronger for estrogen-receptor-positive tumors. A second SNP on chromosome 14q24.1 (rs999737; P = 1.74 x 10(-7)) localizes to RAD51L1, a gene in the homologous recombination DNA repair pathway. We also confirmed associations with loci on chromosomes 2q35, 5p12, 5q11.2, 8q24, 10q26 and 16q12.1. C1 [Thomas, Gilles; Jacobs, Kevin B.; Yeager, Meredith; Wacholder, Sholom; Hutchinson, Amy; Wang, Zhaoming; Yu, Kai; Chatterjee, Nilanjan; Garcia-Closas, Montserrat; Gonzalez-Bosquet, Jesus; Prokunina-Olsson, Ludmila; Ziegler, Regina G.; Brinton, Louise A.; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Hayes, Richard B.; Tucker, Margaret; Fraumeni, Joseph F., Jr.; Hoover, Robert N.; Chanock, Stephen J.; Hunter, David J.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Jacobs, Kevin B.; Hutchinson, Amy; Wang, Zhaoming] NCI, SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, Frederick, MD 21701 USA. [Kraft, Peter; Cox, David G.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Cox, David G.; Hankinson, Susan E.; Willett, Walter C.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Cox, David G.; Hankinson, Susan E.; Willett, Walter C.; Buring, Julie; Lee, I-Min; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Willett, Walter C.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Colditz, Graham A.] Washington Univ, Sch Med, St Louis, MO USA. [Berg, Christine D.] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Buys, Saundra S.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Feigelson, Heather Spencer; Calle, Eugenia E.; Thun, Michael J.; Diver, Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Prentice, Ross; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Jackson, Rebecca] Ohio State Univ, Med Ctr, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Chlebowski, Rowan] Harbor Univ Calif Los Angeles, Med Ctr, Torrance, CA USA. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Peplonska, Beata] Nofer Inst Occupat Med, Lodz, Poland. [Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. [Buring, Julie; Lee, I-Min] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway. [Kumle, Merethe] Univ Tromso, Inst Community Med, Tromso, Norway. [Gerhard, Daniela S.] NCI, Off Canc Genom, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Hunter, David J.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Hunter, DJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM dhunter@hsph.harvard.edu RI Peplonska, Beata/F-6004-2010; Cox, David/A-2023-2009; Tucker, Margaret/B-4297-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Colditz, Graham/0000-0002-7307-0291; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Lissowska, Jolanta/0000-0003-2695-5799; Hayes, Richard/0000-0002-0918-661X FU US National Institutes of Health [CA65725, CA87969, CA49449, CA67262, CA50385, 5UO1CA098233]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; NIH; DHHS; [UO1 CA098710] FX The Nurses' Health Studies are supported by US National Institutes of Health grants CA65725, CA87969, CA49449, CA67262, CA50385 and 5UO1CA098233. We thank B. Egan, L. Egan, H. Judge Ellis, H. Ranu and P. Soule for assistance, and the participants in the Nurses' Health Studies. The WHI program is supported by contracts from the National Heart, Lung and Blood Institute, NIH. We thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at http://www.whi.org. The ACS study is supported by UO1 CA098710. We thank C. Lichtman for data management and the participants on the CPS-II. The US Radiologic Technologists Study (USRT) is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS. The PLCO study is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. We thank P. Prorok, Division of Cancer Prevention, National Cancer Institute, the Screening Center investigators and staff of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and T. Sheehy and staff at SAIC- Frederick. We acknowledge the study participants for their contributions to making this study possible. We thank the radiologic technologists who participated in the study; J. Reid of the American Registry of Radiologic Technologists for continued support of the study; D. Kampa and A. Iwan of the University of Minnesota for study coordination and data collection; B. Kopp and staff at SAIC- Frederick for biospecimen processing; and L. Bowen of Information Management Systems for data management. NR 27 TC 359 Z9 364 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2009 VL 41 IS 5 BP 579 EP 584 DI 10.1038/ng.353 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 438SL UT WOS:000265575600019 PM 19330030 ER PT J AU Ahmed, S Thomas, G Ghoussaini, M Healey, CS Humphreys, MK Platte, R Morrison, J Maranian, M Pooley, KA Luben, R Eccles, D Evans, DG Fletcher, O Johnson, N Silva, ID Peto, J Stratton, MR Rahman, N Jacobs, K Prentice, R Anderson, GL Rajkovic, A Curb, JD Ziegler, RG Berg, CD Buys, SS McCarty, CA Feigelson, HS Calle, EE Thun, MJ Diver, WR Bojesen, S Nordestgaard, BG Flyger, H Dork, T Schurmann, P Hillemanns, P Karstens, JH Bogdanova, NV Antonenkova, NN Zalutsky, IV Bermisheva, M Fedorova, S Khusnutdinova, E Kang, D Yoo, KY Noh, DY Ahn, SH Devilee, P van Asperen, CJ Tollenaar, RAEM Seynaeve, C Garcia-Closas, M Lissowska, J Brinton, L Peplonska, B Nevanlinna, H Heikkinen, T Aittomaki, K Blomqvist, C Hopper, JL Southey, MC Smith, L Spurdle, AB Schmidt, MK Broeks, A van Hien, RR Cornelissen, S Milne, RL Ribas, G Gonzalez-Neira, A Benitez, J Schmutzler, RK Burwinkel, B Bartram, CR Meindl, A Brauch, H Justenhoven, C Hamann, U Chang-Claude, J Hein, R Wang-Gohrke, S Lindblom, A Margolin, S Mannermaa, A Kosma, VM Kataja, V Olson, JE Wang, XS Fredericksen, Z Giles, GG Severi, G Baglietto, L English, DR Hankinson, SE Cox, DG Kraft, P Vatten, LJ Hveem, K Kumle, M Sigurdson, A Doody, M Bhatti, P Alexander, BH Hooning, MJ van den Ouweland, AMW Oldenburg, RA Schutte, M Hall, P Czene, K Liu, JJ Li, YQ Cox, A Elliott, G Brock, I Reed, MWR Shen, CY Yu, JC Hsu, GC Chen, ST Anton-Culver, H Ziogas, A Andrulis, IL Knight, JA Beesley, J Goode, EL Couch, F Chenevix-Trench, G Hoover, RN Ponder, BAJ Hunter, DJ Pharoah, PDP Dunning, AM Chanock, SJ Easton, DF AF Ahmed, Shahana Thomas, Gilles Ghoussaini, Maya Healey, Catherine S. Humphreys, Manjeet K. Platte, Radka Morrison, Jonathan Maranian, Melanie Pooley, Karen A. Luben, Robert Eccles, Diana Evans, D. Gareth Fletcher, Olivia Johnson, Nichola Silva, Isabel dos Santos Peto, Julian Stratton, Michael R. Rahman, Nazneen Jacobs, Kevin Prentice, Ross Anderson, Garnet L. Rajkovic, Aleksandar Curb, J. David Ziegler, Regina G. Berg, Christine D. Buys, Saundra S. McCarty, Catherine A. Feigelson, Heather Spencer Calle, Eugenia E. Thun, Michael J. Diver, W. Ryan Bojesen, Stig Nordestgaard, Borge G. Flyger, Henrik Doerk, Thilo Schuermann, Peter Hillemanns, Peter Karstens, Johann H. Bogdanova, Natalia V. Antonenkova, Natalia N. Zalutsky, Iosif V. Bermisheva, Marina Fedorova, Sardana Khusnutdinova, Elza Kang, Daehee Yoo, Keun-Young Noh, Dong Young Ahn, Sei-Hyun Devilee, Peter van Asperen, Christi J. Tollenaar, R. A. E. M. Seynaeve, Caroline Garcia-Closas, Montserrat Lissowska, Jolanta Brinton, Louise Peplonska, Beata Nevanlinna, Heli Heikkinen, Tuomas Aittomaki, Kristiina Blomqvist, Carl Hopper, John L. Southey, Melissa C. Smith, Letitia Spurdle, Amanda B. Schmidt, Marjanka K. Broeks, Annegien van Hien, Richard R. Cornelissen, Sten Milne, Roger L. Ribas, Gloria Gonzalez-Neira, Anna Benitez, Javier Schmutzler, Rita K. Burwinkel, Barbara Bartram, Claus R. Meindl, Alfons Brauch, Hiltrud Justenhoven, Christina Hamann, Ute Chang-Claude, Jenny Hein, Rebecca Wang-Gohrke, Shan Lindblom, Annika Margolin, Sara Mannermaa, Arto Kosma, Veli-Matti Kataja, Vesa Olson, Janet E. Wang, Xianshu Fredericksen, Zachary Giles, Graham G. Severi, Gianluca Baglietto, Laura English, Dallas R. Hankinson, Susan E. Cox, David G. Kraft, Peter Vatten, Lars J. Hveem, Kristian Kumle, Merethe Sigurdson, Alice Doody, Michele Bhatti, Parveen Alexander, Bruce H. Hooning, Maartje J. van den Ouweland, Ans M. W. Oldenburg, Rogier A. Schutte, Mieke Hall, Per Czene, Kamila Liu, Jianjun Li, Yuqing Cox, Angela Elliott, Graeme Brock, Ian Reed, Malcolm W. R. Shen, Chen-Yang Yu, Jyh-Cherng Hsu, Giu-Cheng Chen, Shou-Tung Anton-Culver, Hoda Ziogas, Argyrios Andrulis, Irene L. Knight, Julia A. Beesley, Jonathan Goode, Ellen L. Couch, Fergus Chenevix-Trench, Georgia Hoover, Robert N. Ponder, Bruce A. J. Hunter, David J. Pharoah, Paul D. P. Dunning, Alison M. Chanock, Stephen J. Easton, Douglas F. CA SEARCH GENICA Consortium KConFab Australian Ovarian Cancer Study TI Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; EXPRESSION AB Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage(1). To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q. C1 [Humphreys, Manjeet K.; Morrison, Jonathan; Pooley, Karen A.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge, England. [Ahmed, Shahana; Ghoussaini, Maya; Healey, Catherine S.; Platte, Radka; Maranian, Melanie; Ponder, Bruce A. J.; Dunning, Alison M.; SEARCH] Univ Cambridge, Dept Oncol, Cambridge, England. [Thomas, Gilles; Jacobs, Kevin; Ziegler, Regina G.; Garcia-Closas, Montserrat; Sigurdson, Alice; Doody, Michele; Bhatti, Parveen; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD USA. [Luben, Robert] Univ Cambridge, EPIC, Dept Publ Hlth & Primary Care, Cambridge, England. [Eccles, Diana] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England. [Evans, D. Gareth] St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. [Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Fletcher, Olivia; Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, London WC1, England. [Stratton, Michael R.] Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge, England. [Jacobs, Kevin] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Jacobs, Kevin] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Prentice, Ross; Anderson, Garnet L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rajkovic, Aleksandar] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Curb, J. David] Univ Hawaii, John A Burns Sch Med, Dept Geriatr Med, Pacific Hlth Res Inst, Honolulu, HI 96822 USA. [Berg, Christine D.] NCI, Canc Prevent Div, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Buys, Saundra S.] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Feigelson, Heather Spencer; Calle, Eugenia E.; Thun, Michael J.; Diver, W. Ryan] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [Bojesen, Stig; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev, Denmark. [Bojesen, Stig; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Copenhagen Gen Populat Study, Herlev, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Dept Breast Surg, Herlev, Denmark. [Doerk, Thilo; Schuermann, Peter; Hillemanns, Peter; Bogdanova, Natalia V.; Bermisheva, Marina] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany. [Karstens, Johann H.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany. [Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Bermisheva, Marina; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia. [Fedorova, Sardana] Russian Acad Med Sci, Yakut Res Ctr, Dept Med Genet, Yakutsk, Russia. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong Young; Ahn, Sei-Hyun] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [van Asperen, Christi J.] Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. [Tollenaar, R. A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands. [Seynaeve, Caroline] Erasmus MC Daniel Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Epidemiol & Canc Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Brinton, Louise] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. [Peplonska, Beata] Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynaecol, Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Hopper, John L.; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Smith, Letitia; Spurdle, Amanda B.; Beesley, Jonathan; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten] Netherlands Canc Inst, Amsterdam, Netherlands. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Ribas, Gloria; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid, Spain. [Gonzalez-Neira, Anna; Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Natl Genotyping Ctr CEGEN, Human Canc Genet Program, Madrid, Spain. [Schmutzler, Rita K.] Spanish Natl Canc Res Ctr CNIO, Natl Genotyping Ctr CEGEN, Human Canc Genet Program, Madrid, Spain. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, D-6900 Heidelberg, Germany. [Burwinkel, Barbara] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Meindl, Alfons] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud; Justenhoven, Christina; GENICA Consortium] Univ Tubingen, Tubingen, Germany. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Chang-Claude, Jenny; Hein, Rebecca] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Wang-Gohrke, Shan] Womens Hosp Univ Ulm, Ulm, Germany. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, S-17176 Stockholm, Sweden. [Margolin, Sara] Karolinska Inst, Dept Pathol & Oncol, S-17176 Stockholm, Sweden. [Mannermaa, Arto; Kosma, Veli-Matti] Univ Kuopio, Pathol & Forens Med & Bioctr Kuopio, Inst Clin Med, FIN-70211 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland. [Olson, Janet E.; Wang, Xianshu; Fredericksen, Zachary; Couch, Fergus] Mayo Clin, Coll Med, Rochester, MN USA. [Giles, Graham G.; Severi, Gianluca; English, Dallas R.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Hankinson, Susan E.; Cox, David G.; Hunter, David J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Hankinson, Susan E.; Cox, David G.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Vatten, Lars J.; Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth, N-7034 Trondheim, Norway. [Kumle, Merethe] Univ Tromso, Inst Community Med, Tromso, Norway. [Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Serv, Minneapolis, MN USA. [Hooning, Maartje J.; Schutte, Mieke] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [van den Ouweland, Ans M. W.; Oldenburg, Rogier A.] Erasmus Univ, Med Ctr, Rotterdam Family Canc Clin, Dept Clin Genet, Rotterdam, Netherlands. [Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Liu, Jianjun; Li, Yuqing] Genome Inst Singapore, Singapore, Singapore. [Elliott, Graeme] Univ Sheffield, Sch Med & Biomed Sci, Inst Canc Studies, Sheffield, S Yorkshire, England. [Reed, Malcolm W. R.] Univ Sheffield, Sch Med & Biomed Sci, Acad Unit Surg Oncol, Sheffield, S Yorkshire, England. [Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Shen, Chen-Yang] China Med Univ, Grad Inst Environm Sci, Taichong, Taiwan. [Yu, Jyh-Cherng; Hsu, Giu-Cheng] Tri Serv Gen Hosp, Taipei, Taiwan. [Chen, Shou-Tung] Changhua Christian Hosp, Changhua, Taiwan. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Ontario Familial Breast Canc Registry, Toronto, ON, Canada. [KConFab; Australian Ovarian Cancer Study] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Ponder, Bruce A. J.] Canc Res UK Cambridge Canc Res Inst, Cambridge, England. [Chanock, Stephen J.] NCI, Adv Technol Ctr, Gaithersburg, MD USA. [Rahman, Nazneen] Inst Canc Res, Sect Canc Genet, Surrey, England. RP Easton, DF (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge, England. EM douglas@srl.cam.ac.uk RI Brinton, Louise/G-7486-2015; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Khusnutdinova, Elza/A-4810-2013; Rahman, Nazneen/D-2802-2013; Gonzalez-Neira, Anna/C-5791-2015; Peplonska, Beata/F-6004-2010; Garcia-Closas, Montserrat /F-3871-2015; Cox, David/A-2023-2009; Spurdle, Amanda/A-4978-2011; Noh, Dong-Young/G-5531-2011; Knight, Julia/A-6843-2012; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Andrulis, Irene/E-7267-2013; Rahman, Nazneen/B-8890-2012; Smith, Letitia /J-9035-2014; OI Brinton, Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Rahman, Nazneen/0000-0003-4376-0440; Czene, Kamila/0000-0002-3233-5695; Lissowska, Jolanta/0000-0003-2695-5799; Luben, Robert/0000-0002-5088-6343; Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Garcia-Closas, Montserrat /0000-0003-1033-2650; Cox, David/0000-0002-2152-9259; Spurdle, Amanda/0000-0003-1337-7897; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188; Evans, Gareth/0000-0002-8482-5784 FU Cancer Research UK [10118, 10124, 11021, A10123, C1287/A10118, C1287/A5260, C1287/A7497, C490/A11021]; Intramural NIH HHS; NCI NIH HHS [R01 CA067262, 5UO1CA098233, CA-06-503, CA-58860, CA-92044, CA-95-011, CA49449, CA50385, CA65725, CA67262, CA87969, K07 CA092044, P01 CA087969, P30 CA062203, P50 CA116201, R01 CA049449, R01 CA050385, R01 CA058860, R01 CA065725, R01 CA102740, R01 CA102740-01A2, R01 CA104021-04, R01 CA122340, U01 CA049449, U01 CA058860, U01 CA067262, U01 CA069398, U01 CA069417, U01 CA069446, U01 CA069467, U01 CA069631, U01 CA069638, U01 CA098233, U01 CA098710, U01 CA69398, U01 CA69417, U01 CA69446, U01 CA69467, U01 CA69631, U01 CA69638, UO1 CA098710, UO1 CA69467] NR 11 TC 299 Z9 302 U1 3 U2 53 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2009 VL 41 IS 5 BP 585 EP 590 DI 10.1038/ng.354 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 438SL UT WOS:000265575600020 PM 19330027 ER PT J AU Huffaker, SJ Chen, JS Nicodemus, KK Sambataro, F Yang, F Mattay, V Lipska, BK Hyde, TM Song, J Rujescu, D Giegling, I Mayilyan, K Proust, MJ Soghoyan, A Caforio, G Callicott, JH Bertolino, A Meyer-Lindenberg, A Chang, J Ji, YJ Egan, MF Goldberg, TE Kleinman, JE Lu, B Weinberger, DR AF Huffaker, Stephen J. Chen, Jingshan Nicodemus, Kristin K. Sambataro, Fabio Yang, Feng Mattay, Venkata Lipska, Barbara K. Hyde, Thomas M. Song, Jian Rujescu, Dan Giegling, Ina Mayilyan, Karine Proust, Morgan J. Soghoyan, Armen Caforio, Grazia Callicott, Joseph H. Bertolino, Alessandro Meyer-Lindenberg, Andreas Chang, Jay Ji, Yuanyuan Egan, Michael F. Goldberg, Terry E. Kleinman, Joel E. Lu, Bai Weinberger, Daniel R. TI A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia SO NATURE MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; GENOTYPE-PHENOTYPE ASSOCIATIONS; DORSOLATERAL PREFRONTAL CORTEX; GENETIC ASSOCIATIONS; WORKING-MEMORY; RELATIVE RISK; K+ CHANNELS; HERG; SIBLINGS; OSCILLATIONS AB Organized neuronal firing is crucial for cortical processing and is disrupted in schizophrenia. Using rapid amplification of 5' complementary DNA ends in human brain, we identified a primate-specific isoform (3.1) of the ether-a-go-go-related K(+) channel KCNH2 that modulates neuronal firing. KCNH2-3.1 messenger RNA levels are comparable to full-length KCNH2 (1A) levels in brain but three orders of magnitude lower in heart. In hippocampus from individuals with schizophrenia, KCNH2-3.1 expression is 2.5-fold greater than KCNH2-1A expression. A meta-analysis of five clinical data sets (367 families, 1,158 unrelated cases and 1,704 controls) shows association of single nucleotide polymorphisms in KCNH2 with schizophrenia. Risk-associated alleles predict lower intelligence quotient scores and speed of cognitive processing, altered memory-linked functional magnetic resonance imaging signals and increased KCNH2-3.1 mRNA levels in postmortem hippocampus. KCNH2-3.1 lacks a domain that is crucial for slow channel deactivation. Overexpression of KCNH2-3.1 in primary cortical neurons induces a rapidly deactivating K+ current and a high-frequency, nonadapting firing pattern. These results identify a previously undescribed KCNH2 channel isoform involved in cortical physiology, cognition and psychosis, providing a potential new therapeutic drug target. C1 [Huffaker, Stephen J.; Chen, Jingshan; Nicodemus, Kristin K.; Sambataro, Fabio; Mattay, Venkata; Lipska, Barbara K.; Hyde, Thomas M.; Song, Jian; Proust, Morgan J.; Callicott, Joseph H.; Meyer-Lindenberg, Andreas; Egan, Michael F.; Goldberg, Terry E.; Kleinman, Joel E.; Weinberger, Daniel R.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Huffaker, Stephen J.; Chen, Jingshan; Nicodemus, Kristin K.; Sambataro, Fabio; Mattay, Venkata; Lipska, Barbara K.; Hyde, Thomas M.; Song, Jian; Meyer-Lindenberg, Andreas; Chang, Jay; Goldberg, Terry E.; Kleinman, Joel E.; Lu, Bai; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Yang, Feng; Chang, Jay; Ji, Yuanyuan; Lu, Bai] NICHD, Sect Neural Dev & Plast, Bethesda, MD USA. [Rujescu, Dan; Giegling, Ina] Univ Munich, Dept Psychiat, D-8000 Munich, Germany. [Mayilyan, Karine; Soghoyan, Armen] Yerevan State Med Univ, Dept Psychiat & Med Psychol, Hlth Minist Armenian, Yerevan, Armenia. [Caforio, Grazia; Bertolino, Alessandro] Univ Bari, Dept Neurol & Psychiat Sci, Sect Mental Disorders, Psychiat Neurosci Grp, Bari, Italy. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Yang, Feng/C-9530-2011; Lu, Bai/A-4018-2012; Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016; Meyer-Lindenberg, Andreas/H-1076-2011; Lipska, Barbara/E-4569-2017 OI Sambataro, Fabio/0000-0003-2102-416X; Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380; Meyer-Lindenberg, Andreas/0000-0001-5619-1123; FU US National Institutes of Health/Cambridge University Health Science FX We thank J. Hardy, J. Duckworth and P. Momeni for technical assistance with high G-C content sequencing. We also thank J. Hardy, D. Goldman, A. Law and W. Chen for their very helpful review of the manuscript. We thank R. Straub and M. Mayhew for their input on statistical genetics analysis, M. Barenboim for help with bioinformatics and M. Herman and S. Mitkus for their help with postmortem tissue. We are extremely grateful for the assistance of G. Liu and S. Chen in the cloning and sequencing of KCNH2-3.1. We also would like to thank H.-J. Moller, P. Muglia and coworkers at the Department of Psychiatry, Ludwig Maximilians University for their help with subject recruitment and evaluation. S. J. Huffaker was partially supported by the US National Institutes of Health/Cambridge University Health Science Scholars and Medical Scientist Training Programs. Recruitment of the individuals with schizophrenia at Ludwig Maximilians University was supported by GlaxoSmithKline. Human fetal tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland. NR 57 TC 140 Z9 142 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2009 VL 15 IS 5 BP 509 EP 518 DI 10.1038/nm.1962 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 443DB UT WOS:000265889300029 PM 19412172 ER PT J AU Economopoulou, M Langer, HF Celeste, A Orlova, VV Choi, EY Ma, MC Vassilopoulos, A Callen, E Deng, CX Bassing, CH Boehm, M Nussenzweig, A Chavakis, T AF Economopoulou, Matina Langer, Harald F. Celeste, Arkady Orlova, Valeria V. Choi, Eun Young Ma, Mingchao Vassilopoulos, Athanassios Callen, Elsa Deng, Chuxia Bassing, Craig H. Boehm, Manfred Nussenzweig, Andre Chavakis, Triantafyllos TI Histone H2AX is integral to hypoxia-driven neovascularization SO NATURE MEDICINE LA English DT Article ID DNA-DAMAGE RESPONSE; REPLICATION CHECKPOINT; GENOMIC INSTABILITY; ATR; ANGIOGENESIS; PHOSPHORYLATION; INHIBITION; REOXYGENATION; PERMEABILITY; RECOGNITION AB H2A histone family member X (H2AX, encoded by H2AFX) and its C-terminal phosphorylation (gamma-H2AX) participates in the DNA damage response and mediates DNA repair(1-6). Hypoxia is a physiological stress that induces a replication-associated DNA damage response(7). Moreover, hypoxia is the major driving force for neovascularization(8), as the hypoxia-mediated induction of vascular growth factors triggers endothelial cell proliferation(8). Here we studied the role of the hypoxia-induced DNA damage response in endothelial cell function and in hypoxia-driven neovascularization in vivo. Hypoxia induced replication-associated generation of gamma-H2AX in endothelial cells in vitro and in mice. Both in cultured cells and in mice, endothelial cell proliferation under hypoxic conditions was reduced by H2AX deficiency. Whereas developmental angiogenesis was not affected in H2afx(-/-) mice, hypoxia-induced neovascularization during pathologic proliferative retinopathy, in response to hind limb ischemia or during tumor angiogenesis was substantially lower in H2afx(-/-) mice. Moreover, endothelial-specific H2afx deletion resulted in reduced hypoxia-driven retina neovascularization and tumor neovascularization. Our findings establish that H2AX, and hence activation of the DNA repair response, is needed for endothelial cells to maintain their proliferation under hypoxic conditions and is crucial for hypoxia-driven neovascularization. C1 [Economopoulou, Matina; Langer, Harald F.; Celeste, Arkady; Orlova, Valeria V.; Choi, Eun Young; Callen, Elsa; Nussenzweig, Andre; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Ma, Mingchao; Boehm, Manfred] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. [Vassilopoulos, Athanassios; Deng, Chuxia] NIDDKD, Genet Dev & Dis Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Bassing, Craig H.] Univ Penn, Sch Med, Dept Pathol & Lab Med,Abramson Family Canc Res In, Ctr Childhood Canc Res,Childrens Hosp Philadelphi, Philadelphia, PA 19104 USA. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Orlova, Valeria/C-6065-2014 OI Orlova, Valeria/0000-0002-1169-2802 FU US National Institutes of Health National Cancer Institute; German Academy of Sciences (Leopoldina) FX This research was supported by the Intramural Research Program of the US National Institutes of Health National Cancer Institute. H. F. L. was supported by the German Academy of Sciences (Leopoldina). We would like to acknowledge M. E. Kruhlak for the help with microscopy, D. Winkler and S. Kaul for help with genotyping, G. Tosato for help with Matrigel experiments, F. Alt (Harvard University) for providing the H2afx floxed mice and A. Singer and D. S. Singer for critically reading the manuscript. NR 33 TC 59 Z9 62 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 2009 VL 15 IS 5 BP 553 EP 558 DI 10.1038/nm.1947 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 443DB UT WOS:000265889300034 PM 19377486 ER PT J AU Kriegeskorte, N Simmons, WK Bellgowan, PSF Baker, CI AF Kriegeskorte, Nikolaus Simmons, W. Kyle Bellgowan, Patrick S. F. Baker, Chris I. TI Circular analysis in systems neuroscience: the dangers of double dipping SO NATURE NEUROSCIENCE LA English DT Article ID FUNCTIONAL LOCALIZERS; FMRI DATA; BRAIN; CORTEX AB A neuroscientific experiment typically generates a large amount of data, of which only a small fraction is analyzed in detail and presented in a publication. However, selection among noisy measurements can render circular an otherwise appropriate analysis and invalidate results. Here we argue that systems neuroscience needs to adjust some widespread practices to avoid the circularity that can arise from selection. In particular, 'double dipping', the use of the same dataset for selection and selective analysis, will give distorted descriptive statistics and invalid statistical inference whenever the results statistics are not inherently independent of the selection criteria under the null hypothesis. To demonstrate the problem, we apply widely used analyses to noise data known to not contain the experimental effects in question. Spurious effects can appear in the context of both univariate activation analysis and multivariate pattern-information analysis. We suggest a policy for avoiding circularity. C1 [Kriegeskorte, Nikolaus; Simmons, W. Kyle; Bellgowan, Patrick S. F.; Baker, Chris I.] US Natl Inst Mental Hlth, Lab Brain & Cognit, Bethesda, MD USA. RP Kriegeskorte, N (reprint author), US Natl Inst Mental Hlth, Lab Brain & Cognit, Bethesda, MD USA. EM nikokriegeskorte@gmail.com; bakerchris@mail.nih.gov RI Simmons, William/K-8925-2015; OI Simmons, William/0000-0002-0399-9003; Kriegeskorte, Nikolaus/0000-0001-7433-9005; Baker, Chris/0000-0001-6861-8964 FU US National Institute of Mental Health FX We would like to thank P. A. Bandettini, R. W. Cox, J.V. Haxby, D.J. Kravitz, A. Martin, R. A. Poldrack, R. D. Raizada, Z.S. Saad, J.T. Serences and E. Vul for helpful discussions. This work was supported by the Intramural Research Program of the US National Institute of Mental Health. NR 24 TC 1037 Z9 1043 U1 5 U2 80 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2009 VL 12 IS 5 BP 535 EP 540 DI 10.1038/nn.2303 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 438SJ UT WOS:000265575400006 PM 19396166 ER PT J AU Paradiso, K Wu, LG AF Paradiso, Kenneth Wu, Ling-Gang TI Small voltage changes at nerve terminals travel up axons to affect action potential initiation SO NATURE NEUROSCIENCE LA English DT Article ID TRANSMITTER RELEASE; PRESYNAPTIC CA2+; RAT; MODULATION; RECEPTORS; ANALOG AB Nerve terminals are generally considered to be the destination points for electrical signals, which propagate unidirectionally from the soma to nerve terminals. We found that small hyperpolarizations or depolarizations (similar to 10 mV) generated under physiological conditions in rat nerve terminals backpropagated up the axon (similar to 400-800 mu m) and changed the threshold for initiating action potentials and thus firing patterns. These results suggest a mechanism for information processing in neurons and neuronal circuits. C1 [Paradiso, Kenneth; Wu, Ling-Gang] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA. RP Paradiso, K (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA. EM kenparadiso@gmail.com; wul@ninds.nih.gov OI Paradiso, Kenneth/0000-0002-6396-9412 FU National Institute of Neurological Disorders and Stroke Intramural Program [K22NS051401] FX We thank J. Diamond, A. Elhamdani, B. McNeil, D. Robinson and J. Xu for insightful comments. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Program and a K22 Award to K. P. (K22NS051401). NR 15 TC 12 Z9 12 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2009 VL 12 IS 5 BP 541 EP 543 DI 10.1038/nn.2301 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 438SJ UT WOS:000265575400007 PM 19349974 ER PT J AU Grimes, WN Li, W Chavez, AE Diamond, JS AF Grimes, William N. Li, Wei Chavez, Andres E. Diamond, Jeffrey S. TI BK channels modulate pre- and postsynaptic signaling at reciprocal synapses in retina SO NATURE NEUROSCIENCE LA English DT Article ID CA2+-ACTIVATED K+ CHANNELS; AMACRINE CELLS; MAMMALIAN RETINA; TRANSMITTER RELEASE; GLUTAMATE RECEPTORS; CALCIUM-CHANNELS; OLFACTORY-BULB; BIPOLAR CELLS; BETA-SUBUNITS; SK CHANNELS AB In the mammalian retina, A17 amacrine cells provide reciprocal inhibitory feedback to rod bipolar cells, thereby shaping the time course of visual signaling in vivo. Previous results have indicated that A17 feedback can be triggered by Ca(2+) influx through Ca(2+)-permeable AMPA receptors and can occur independently of voltage-gated Ca(2+) (Ca(v)) channels, whose presence and functional role in A17 dendrites have not yet been explored. We combined electrophysiology, calcium imaging and immunohistochemistry and found that L-type Ca(v) channels in rat A17 amacrine cells were located at the sites of reciprocal synaptic feedback and that their contribution to GABA release was diminished by large-conductance Ca(2+)-activated potassium (BK) channels, which suppress postsynaptic depolarization in A17s and limit Ca(v) channel activation. We also found that BK channels, by limiting GABA release from A17s, regulate the flow of excitatory synaptic transmission through the rod pathway. C1 [Grimes, William N.; Chavez, Andres E.; Diamond, Jeffrey S.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, Bethesda, MD 20824 USA. [Grimes, William N.] Univ Maryland, NIH, Biophys Grad Partnership Program, College Pk, MD 20742 USA. [Li, Wei] NEI, Unit Retinal Neurophysiol, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, Bethesda, MD 20824 USA. EM diamondj@ninds.nih.gov RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 FU US National Institute of Neurological Disorders and Stroke Intramural Research Program FX We thank C. McBain for critically reading the manuscript, members of the Diamond and Isaac laboratories for helpful discussions and E. Compton-Daw for assistance with spectrophotometry. This work was supported by the US National Institute of Neurological Disorders and Stroke Intramural Research Program. NR 34 TC 36 Z9 36 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2009 VL 12 IS 5 BP 585 EP 592 DI 10.1038/nn.2302 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 438SJ UT WOS:000265575400015 PM 19363492 ER PT J AU Gutierrez, ME Kummar, S Giaccone, G AF Gutierrez, Martin E. Kummar, Shivaani Giaccone, Giuseppe TI Next generation oncology drug development: opportunities and challenges SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; CLINICAL-TRIAL DESIGN; RANDOMIZED DISCONTINUATION TRIAL; PREVIOUSLY TREATED PATIENTS; TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; CUTANEOUS MELANOMA; RESPONSE CRITERIA; TARGETED THERAPY AB The optimal development of novel molecularly targeted agents for the treatment of cancer requires a re-evaluation of the current drug development paradigm. selection of patients, optimal biologic dose versus maximum tolerated dose, definition of response and clinical benefit and trial designs that address these considerations are the focus of debate in the field of early cancer therapeutics. we present a review of the opportunities and challenges facing drug development in oncology through the phases of clinical development starting with first-in-human trials. C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 49 TC 47 Z9 49 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD MAY PY 2009 VL 6 IS 5 BP 259 EP 265 DI 10.1038/nrclinonc.2009.38 PG 7 WC Oncology SC Oncology GA 442PT UT WOS:000265853800009 PM 19390552 ER PT J AU Marini, JC AF Marini, Joan C. TI BONE Use of bisphosphonates in children-proceed with caution SO NATURE REVIEWS ENDOCRINOLOGY LA English DT Editorial Material ID OSTEOGENESIS IMPERFECTA; INDUCED OSTEOPETROSIS; PAMIDRONATE; THERAPY AB A clinical review of studies on bisphosphonate therapy for pediatric osteoporosis has revealed that they increase BMD, but whether they also improve fracture rates or functions of daily life is unclear. can the findings of this clinical review help inform clinicians whether, when and how to use these agents in children? C1 NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHHD, Bone & Extracellular Matrix Branch, NIH, Bldg 10,Room 10N260,9000 Rockville Pike, Bethesda, MD 20892 USA. EM marinij@mail.nih.gov NR 10 TC 24 Z9 24 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5029 J9 NAT REV ENDOCRINOL JI Nat. Rev. Endocrinol. PD MAY PY 2009 VL 5 IS 5 BP 241 EP 243 DI 10.1038/nrendo.2009.58 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442PW UT WOS:000265854100002 PM 19444252 ER PT J AU Sullivan, NJ Martin, JE Graham, BS Nabel, GJ AF Sullivan, Nancy J. Martin, Julie E. Graham, Barney S. Nabel, Gary J. TI Correlates of protective immunity for Ebola vaccines: implications for regulatory approval by the animal rule SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID VIRUS-INFECTED PATIENTS; T-CELL RESPONSES; NONHUMAN-PRIMATES; HEMORRHAGIC-FEVER; GUINEA-PIGS; NUCLEOPROTEIN; IMMUNIZATION; LYMPHOCYTES; ANTIBODIES; MICE AB Ebola virus infection is a highly lethal disease for which there are no effective therapeutic or preventive treatments. Several vaccines have provided immune protection in laboratory animals, but because outbreaks occur unpredictably and sporadically, vaccine efficacy cannot be proven in human trials, which is required for traditional regulatory approval. The Food and Drug Administration has introduced the 'animal rule', to allow laboratory animal data to be used to show efficacy when human trials are not logistically feasible. In this Review, we describe immune correlates of vaccine protection against Ebola virus in animals. This research provides a basis for bridging the gap from basic research to human vaccine responses in support of the licensing of vaccines through the animal rule. C1 [Sullivan, Nancy J.] NIAID, Biodef Res Sect, NIH, Bethesda, MD 20892 USA. [Martin, Julie E.; Graham, Barney S.] NIAID, Clin Trials Core Lab, NIH, Bethesda, MD 20892 USA. [Martin, Julie E.; Graham, Barney S.] NIAID, Viral Pathogenesis Lab, NIH, Bethesda, MD 20892 USA. [Nabel, Gary J.] NIAID, Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sullivan, NJ (reprint author), NIAID, Biodef Res Sect, NIH, 40 Convent Dr,MSC 3005, Bethesda, MD 20892 USA. EM nsullivan@nih.gov NR 45 TC 101 Z9 109 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD MAY PY 2009 VL 7 IS 5 BP 393 EP 400 DI 10.1038/nrmicro2129 PG 8 WC Microbiology SC Microbiology GA 441QG UT WOS:000265783400015 PM 19369954 ER PT J AU Brennan, AR Yuan, PX Dickstein, DL Rocher, AB Hof, PR Manji, H Arnsten, AFT AF Brennan, Avis R. Yuan, Peixiong Dickstein, Dara L. Rocher, Anne B. Hof, Patrick R. Manji, Husseini Arnsten, Amy F. T. TI Protein kinase C activity is associated with prefrontal cortical decline in aging SO NEUROBIOLOGY OF AGING LA English DT Article DE Prefrontal cortex; Aging; Working memory; Protein kinase C; Dendritic spines; Chelerythrine; Dendrites ID AGE-RELATED-CHANGES; WORKING-MEMORY; RHESUS-MONKEY; SPATIAL MEMORY; QUANTITATIVE-ANALYSIS; DENDRITIC MORPHOLOGY; REPEATED STRESS; FRONTAL-CORTEX; MACACA-MULATTA; SPINE CHANGES AB Aging is associated with deficiencies in the prefrontal cortex, including working memory impairment and compromised integrity of neuronal dendrites. Although protein kinase C (PKC) is implicated in structural plasticity, and overactivation of PKC results in working memory impairments in young animals, the role of PKC in prefrontal cortical impairments in the aged has not been examined. This study provides the first evidence that PKC activity is associated with prefrontal cortical dysfunction in aging. Pharmacological inhibition of PKC with chelerythrine rescued working memory impairments in aged rats and enhanced working memory in aged rhesus monkeys. Improvement correlated with age, with older monkeys demonstrating a greater degree of improvement following PKC inhibition. Furthermore, PKC activity within the prefrontal cortex was inversely correlated with the length of basal dendrites of prefrontal cortical neurons, as well as with working memory performance in aged rats. Together these findings indicate that PKC is dysregulated in aged animals and that PKC inhibitors may be useful in the treatment of cognitive deficits in the elderly. (C) 2007 Elsevier Inc. All rights reserved. C1 [Brennan, Avis R.; Arnsten, Amy F. T.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06511 USA. [Yuan, Peixiong; Manji, Husseini] NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. [Dickstein, Dara L.; Rocher, Anne B.; Hof, Patrick R.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. RP Arnsten, AFT (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St,SHM C300, New Haven, CT 06511 USA. EM avis.brennan@yale.edu; amy.arnsten@yale.edu RI Dickstein, Dara/F-3036-2013 FU NIH [R37 AG06036]; Claude D. Pepper Older Americans Independence Center, Yale University School of Medicine, NIH/NIA [P30 AG21342]; National Science Foundation Graduate Research Fellowship; American Foundation of Aging Research Student Research Fellowship; NIB [AG02219, AG05138] FX The authors would like to thank Tracy Sadlon, Lisa Ciavarella, Sam Johnson, and Jessica Thomas for their invaluable technical assistance. The research was supported by NIH grants R37 AG06036 and the Claude D. Pepper Older Americans Independence Center, Yale University School of Medicine (P30 AG21342 NIH/NIA) to A.F.T.A; The National Science Foundation Graduate Research Fellowship and American Foundation of Aging Research Student Research Fellowship to A.R.B.; and NIB grants AG02219 and AG05138 to RR.H. NR 57 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY PY 2009 VL 30 IS 5 BP 782 EP 792 DI 10.1016/j.neurobiolaging.2007.08.020 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 430VU UT WOS:000265018700011 PM 17919783 ER PT J AU Duncko, R Johnson, L Merikangas, K Grillon, C AF Duncko, Roman Johnson, Linda Merikangas, Kathleen Grillon, Christian TI Working memory performance after acute exposure to the cold pressor stress in healthy volunteers SO NEUROBIOLOGY OF LEARNING AND MEMORY LA English DT Article DE Stress; Working memory; Reaction time; Cortisol; Arousal ID PSYCHOSOCIAL STRESS; PREFRONTAL CORTEX; HPA AXIS; CORTISOL; MEN; HIPPOCAMPUS; ACTIVATION; RETRIEVAL; ATTENTION; ANXIETY AB Effects of acute stress exposure on learning and memory have been frequently studied in both animals and humans. However, only a few studies have focused specifically on working memory performance and the available data are equivocal. The present study examined working memory performance during the Sternberg item recognition task after exposure to a predominantly adrenergic stressor. Twenty four healthy subjects were randomly assigned to a stress group or a control group. The stress group was exposed to the cold pressor stress test (CPS; i.e. insertion of the dominant hand into ice water for 60s), while 37 degrees C warm water was used with the control group. Twenty minutes after the stress exposure, working memory performance was tested with the Sternberg item recognition task with three levels of cognitive load. Sympathetic nervous system and hypothalamic pituitary adrenocortical (HPA) axis activation during CPS, were assessed by measuring heart rate and salivary cortisol before and during (heart rate) or 30 min after (cortisol) the stress procedure. Exposure to the CPS test was associated with a significant increase in heart rate but no increase in salivary cortisol. Participants exposed to the stress procedure showed significantly shorter reaction times during trials with higher cognitive load but tended to show higher false alarm rates than control subjects. The present results indicate that exposure to CPS can be associated with signs of both enhanced and impaired working memory performance. The observed behavioral pattern might represent a form of streamlined information processing advantageous in a threatening situation. Published by Elsevier Inc. C1 [Duncko, Roman; Merikangas, Kathleen] NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, Bethesda, MD 20892 USA. [Johnson, Linda] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Grillon, Christian] NIMH, Sect Cognit Psychophysiol, Intramural Res Program, Bethesda, MD 20892 USA. RP Duncko, R (reprint author), NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM dunckor@mail.nih.gov FU Intramural Program of the National Institute of Mental Health; National Institutes of Health FX This research was supported in part by the Intramural Program of the National Institute of Mental Health, National Institutes of Health. NR 31 TC 45 Z9 46 U1 6 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1074-7427 J9 NEUROBIOL LEARN MEM JI Neurobiol. Learn. Mem. PD MAY PY 2009 VL 91 IS 4 BP 377 EP 381 DI 10.1016/j.nlm.2009.01.006 PG 5 WC Behavioral Sciences; Neurosciences; Psychology; Psychology, Multidisciplinary SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 431HH UT WOS:000265051700005 PM 19340949 ER PT J AU Kim, J Horwitz, B AF Kim, Jieun Horwitz, Barry TI How well does structural equation modeling reveal abnormal brain anatomical connections? An fMRI simulation study SO NEUROIMAGE LA English DT Article ID ALTERED EFFECTIVE CONNECTIVITY; MILD COGNITIVE IMPAIRMENT; EMISSION TOMOGRAPHIC DATA; WORKING-MEMORY NETWORK; FUNCTIONAL MRI DATA; ALZHEIMERS-DISEASE; VISUAL PATHWAYS; NEURAL BASIS; AUTISM; DEMENTIA AB Many brain disorders result from alterations in the strength of anatomical connectivity between different brain regions. This study investigates whether such alterations can be revealed by examining differences in interregional effective connectivity between patient and normal subjects. We applied one prominent effective connectivity method - Structural Equation Modeling (SEM) - to simulated functional MRI (fMRI) timeseries from a neurobiologically realistic network model in which the anatomical connectivity is known and can be manipulated. These timeseries were simulated for two task conditions, a delayed match-to-sample (DMS) task and passive-viewing, and for "normal subjects" and "patients" who had one weakened anatomical connection in the neural network model. SEM results were compared between task conditions as well as between groups. A significantly reduced effective connectivity corresponding to the weakened anatomical connection during the DMS task was found. We also obtained a significantly reduced set of effective connections in the patient networks for anatomical connections "downstream" from the weakened linkage. However, some "upstream" effective connections were significantly larger in the patient group relative to normals. Finally, we found that of the SEM model measures we examined, the total error variance was the best at distinguishing a patient network from a normal network. These results suggest that caution is necessary in applying effective connectivity methods to fMRI data obtained from non-normal populations, and emphasize that functional interactions among network elements can appear as abnormal even if only part of a network is damaged. Published by Elsevier Inc. C1 [Kim, Jieun; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Horwitz, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, Natl Inst Hlth, Bldg 10,Rm 8S235,MSC 1407, Bethesda, MD 20892 USA. EM horwitzb@mail.nih.gov FU NIDCD/NIH FX The work was supported by the NIDCD/NIH Intramural Research Program. We wish to thank Dr. Ajay Pillai for a critical reading of the manuscript. NR 54 TC 18 Z9 18 U1 5 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2009 VL 45 IS 4 BP 1190 EP 1198 DI 10.1016/j.neuroimage.2009.01.006 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 421SL UT WOS:000264378500016 PM 19349234 ER PT J AU Volkow, ND Tomasi, D Wang, GJ Telang, F Fowler, JS Wang, RL Logan, J Wong, C Jayne, M Swanson, JM AF Volkow, Nora D. Tomasi, Dardo Wang, Gene-Jack Telang, Frank Fowler, Joanna S. Wang, Ruiliang L. Logan, Jean Wong, Christopher Jayne, Millard Swanson, James M. TI Hyperstimulation of striatal D2 receptors with sleep deprivation: Implications for cognitive impairment SO NEUROIMAGE LA English DT Article DE Dopamine D2 receptors; Raclopride; Visual attention; PET; fMRI; Default network; Thalamus ID DOPAMINE D-2/D-3 RECEPTORS; LATERAL GENICULATE-NUCLEUS; MEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; EMOTION-INDUCED CHANGES; VISUAL-CORTEX; HUMAN BRAIN; WORKING-MEMORY; ATTENTIONAL IMPAIRMENTS; TASK-PERFORMANCE AB Sleep deprivation interferes with cognitive performance but the mechanisms are poorly understood. We recently reported that one night of sleep deprivation increased dopamine in striatum (measured with [(11)C] raclopride, a PET radiotracer that competes with endogenous dopamine for binding to D2 receptors) and that these increases were associated with impaired performance in a visual attention task. To better understand this association here we evaluate the relationship between changes in striatal dopamine (measured as changes in D2 receptor availability using PET and [(11)C] raclopride) and changes in brain activation to a visual attention task (measured with BOLD and fMRI) when performed during sleep deprivation versus during rested wakefulness. We find that sleep induced changes in striatal dopamine were associated with changes in cortical brain regions modulated by dopamine (attenuated deactivation of anterior cingulate gyrus and insula) but also in regions that are not recognized targets of dopaminergic modulation (attenuated activation of inferior occipital cortex and cerebellum). Moreover, the increases in striatal dopamine as well as its associated regional activation and deactivation patterns correlated negatively with performance accuracy. These findings therefore suggest that hyperstimulation of D2 receptors in striatum may contribute to the impairment in visual attention during sleep deprivation. Thus, while dopamine increases in prefrontal regions (including stimulation of D1 receptors) may facilitate attention our findings suggest that hyperstimulation of D2 receptors in striatum may impair it. Alternatively, these associations may reflect a compensatory striatal dopamine response (to maintain arousal) that is superimposed on a larger response to sleep deprivation. (C) 2009 Elsevier Inc. All rights reserved. C1 [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Volkow, Nora D.; Tomasi, Dardo; Telang, Frank; Jayne, Millard] NIAAA, Bethesda, MD 20892 USA. [Wang, Gene-Jack; Fowler, Joanna S.; Wang, Ruiliang L.; Logan, Jean; Wong, Christopher] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Swanson, James M.] Univ Calif Irvine, Child Dev Ctr, Irvine, CA 92612 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015; OI Logan, Jean/0000-0002-6993-9994 FU Intramural NIH HHS [Z01 AA000550-04] NR 68 TC 34 Z9 35 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2009 VL 45 IS 4 BP 1232 EP 1240 DI 10.1016/j.neuroimage.2009.01.003 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 421SL UT WOS:000264378500020 PM 19349237 ER PT J AU Kumar, R Riddle, L Griffin, SA Grundt, P Newman, AH Luedtke, RR AF Kumar, Rakesh Riddle, Lindsay Griffin, Suzy A. Grundt, Peter Newman, Amy Hauck Luedtke, Robert R. TI Evaluation of the D3 dopamine receptor selective antagonist PG01037 on L-dopa-dependent abnormal involuntary movements in rats- SO NEUROPHARMACOLOGY LA English DT Review DE Parkinson's Disease; Dyskinesia; L-dopa; Dopamine receptors; D3 dopamine receptors ID LEVODOPA-INDUCED DYSKINESIAS; INDUCED MOTOR COMPLICATIONS; PARKINSONS-DISEASE; THERAPEUTIC AGENTS; MESSENGER-RNA; RISK-FACTORS; SENSITIZATION; DEGENERATION; WAY-100635; PRIMATES AB The D3 dopamine receptor selective antagonist PG01037 has been evaluated for the ability to attenuate L-dopa-associated abnormal involuntary movements (AIMs) in unilaterally lesioned male Sprague-Dawley rats, which is a model of L-dopa-dependent dyskinesia in patients with Parkinson's Disease. The intrinsic activity of PG01037 was determined using a) a forskolin-dependent adenylyl cyclase inhibition assay with transfected HEK 293 cells expressing either the human D2Long or D3 dopamine receptor subtype and b) an assay for agonist-associated mitogenesis. For the initial experiments, the 5-HT1A receptor selective partial agonist buspirone was used as a positive control to verify our ability to quantitate changes in total AIMs and AIMs minus locomotor scores. Subcutaneous (s.c.) administration of PG01037 was found to have minimal effect on AIMs score. However, it was observed that the in vivo efficacy of PG01037 increased when administered by intraperitoneal (i.p.) injection 15 min after L-dopa/benserazide ad ministration, as compared to a 60 min, 30 min or 0 min pretreatment. It was also found that i.p. administration of PG01037 could inhibit involuntary movements after they had achieved maximum intensity. PG01037 was found to attenuate AIM scores in these animals in a dose dependent manner with IC(50) value equal to a) 7.4 mg/kg following L-dopa/benserazide administration (8 mg/kg each, i.p.) and b) 18.4 mg/kg following the administration of apomorphine (0.05 mg/kg, s.c.). However, PG01037 did not effectively inhibit SKF 81297-dependent abnormal involuntary movements. Rotarod studies indicate that PGO1037 at a dose of 10 mg/kg did not adversely affect motor coordination of the unilaterally lesioned rats. Evaluation of lesioned rats using a cylinder test behavioral paradigm indicated that PG01037 did not dramatically attenuate the beneficial effects Of L-dopa. These studies suggest that D3 dopamine receptor selective antagonists are potential pharmacotherapeutic candidates for the treatment of L-dopa-associated dyskinesia in patients with Parkinson's Disease. (C) 2009 Published by Elsevier Ltd. C1 [Kumar, Rakesh; Riddle, Lindsay; Griffin, Suzy A.; Luedtke, Robert R.] Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Ft Worth, TX 76107 USA. [Grundt, Peter; Newman, Amy Hauck] NIDA IRP, Med Chem Sect, Baltimore, MD 21224 USA. RP Luedtke, RR (reprint author), Univ N Texas, Hlth Sci Ctr, Dept Pharmacol & Neurosci, 3500 Camp Bowie, Ft Worth, TX 76107 USA. EM rluedtke@hsc.unt.edu FU Michael J. Fox Foundation for Parkinson's Research; National Institute on Drug Abuse-Intramural Research Program FX The authors would like to thank Dr. Steven Gold and Mr. Brian Potts for their insightful discussions on the AIMS scoring system. We would like to thank Dr. Eunson Jung, for her assistance with the rotarod experiments. This research was supported by a Community Fast Track 2006 Award from the Michael J. Fox Foundation for Parkinson's Research and the National Institute on Drug Abuse-Intramural Research Program. NR 46 TC 22 Z9 22 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD MAY-JUN PY 2009 VL 56 IS 6-7 BP 944 EP 955 DI 10.1016/j.neuropharm.2009.01.020 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 454SF UT WOS:000266702200003 PM 19371585 ER PT J AU Ferraina, S Battaglia-Mayer, A Genovesio, A Archambault, P Caminiti, R AF Ferraina, Stefano Battaglia-Mayer, Alexandra Genovesio, Aldo Archambault, Philippe Caminiti, Roberto TI Parietal encoding of action in depth SO NEUROPSYCHOLOGIA LA English DT Review DE Eye movement; Hand movement; 3D space; Coordinates system; On-line control; Parietal cortex ID EYE-HAND COORDINATION; VISUAL FORM AGNOSIA; LIMB POSITION DRIFT; POSTERIOR PARIETAL; ARM MOVEMENTS; REACHING MOVEMENTS; MOTOR CORTEX; ASSOCIATION CORTEX; TARGET LOCATION; CORTICAL REPRESENTATION AB The posterior parietal cortex is a crucial node in the process of coordinates transformation for the visual control of eye and hand movements. This conviction stems from both neurophysiological studies in the behaving monkey and from the analysis of the consequences of parietal lobe lesions in humans. Despite an extensive literature concerning varying aspects of the composition and control of eye and hand movements, there is little information about the physiological processes responsible for encoding target distance and hand movement in depth or about their control and impairment in parietal patients. This review is an attempt to provide a comprehensive picture from the fragmentary material existing on this issue in the literature. This should serve as a basis for discussion of what we consider to be a prototypical function of the dorsal visuomotor stream in the primate brain, that of encoding eye and hand movement in depth. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Ferraina, Stefano; Battaglia-Mayer, Alexandra; Genovesio, Aldo; Archambault, Philippe; Caminiti, Roberto] Univ Rome, Dept Physiol & Pharmacol, I-00185 Rome, Italy. [Ferraina, Stefano; Battaglia-Mayer, Alexandra; Genovesio, Aldo; Archambault, Philippe; Caminiti, Roberto] Univ Rome, SAPIENZA, CSFM, I-00185 Rome, Italy. [Genovesio, Aldo] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. [Archambault, Philippe] McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ, Canada. RP Caminiti, R (reprint author), Univ Rome, Dept Physiol & Pharmacol, Piazzale Aldo Moro 5, I-00185 Rome, Italy. EM roberto.caminiti@uniroma1.it RI Archambault, Philippe/F-4675-2010; Battaglia-Mayer, Alexandra/B-3749-2010 OI Archambault, Philippe/0000-0002-8656-4477; NR 147 TC 17 Z9 17 U1 7 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAY PY 2009 VL 47 IS 6 SI SI BP 1409 EP 1420 DI 10.1016/j.neuropsychologia.2008.12.028 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 441NB UT WOS:000265774800003 PM 19154747 ER PT J AU Law, AJ Pei, Q Walker, M Gordon-Andrews, H Weickert, CS Feldon, J Pryce, CR Harrison, PJ AF Law, Amanda J. Pei, Qi Walker, Mary Gordon-Andrews, Helen Weickert, Cyndi Shannon Feldon, Joram Pryce, Christopher R. Harrison, Paul J. TI Early Parental Deprivation in the Marmoset Monkey Produces Long-Term Changes in Hippocampal Expression of Genes Involved in Synaptic Plasticity and Implicated in Mood Disorder SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE depression; GAP-43; hippocampus; mRNA; 5-HT(1A) receptor; VGAT ID RECEPTOR MESSENGER-RNA; POSITRON-EMISSION-TOMOGRAPHY; EARLY-LIFE STRESS; MAJOR DEPRESSIVE DISORDER; VESICULAR GLUTAMATE TRANSPORTER; NEUROTROPHIC FACTOR; BIPOLAR DISORDER; MATERNAL SEPARATION; RAT HIPPOCAMPUS; NEUROPSYCHIATRIC DISORDERS AB In mood disorder, early stressors including parental separation are vulnerability factors, and hippocampal involvement is prominent. In common marmoset monkeys, daily parental deprivation during infancy produces a prodepressive state of increased basal activity and reactivity in stress systems and mild anhedonia that persists at least to adolescence. Here we examined the expression of eight genes, each implicated in neural plasticity and in the pathophysiology of mood disorder, in the hippocampus of these same adolescent marmosets, relative to their normally reared sibling controls. We also measured hippocampal volume. Early deprivation led to decreases in hippocampal growth-associated protein-43 (GAP-43) mRNA, serotonin 1A receptor (5-HT(1A)R) mRNA and binding ([(3)H]WAY100635), and to increased vesicular GABA transporter mRNA. Brain-derived neurotrophic factor (BDNF), synaptophysin, vesicular glutamate transporter 1 (VGluT1), microtubule-associated protein-2, and spinophilin transcripts were unchanged. There were some correlations with in vivo biochemical and behavioral indices, including VGluT1 mRNA with reward-seeking behavior, and serotonin 1A receptor mRNA with CSF cortisol. Early deprivation did not affect hippocampal volume. We conclude that early deprivation in a nonhuman primate, in the absence of subsequent stressors, has a long-term effect on the hippocampal expression of genes implicated in synaptic function and plasticity. The reductions in GAP-43 and serotonin 1A receptor expressions are comparable with findings in mood disorder, supporting the possibility that the latter reflect an early developmental contribution to disease vulnerability. Equally, the negative results suggest that other features of mood disorder, such as decreased hippocampal volume and BDNF expression, are related to different aspects of the pathophysiological process. C1 [Law, Amanda J.; Pei, Qi; Walker, Mary; Gordon-Andrews, Helen; Harrison, Paul J.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. [Law, Amanda J.; Weickert, Cyndi Shannon] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Feldon, Joram; Pryce, Christopher R.] Swiss Fed Inst Technol, Lab Behav Neurobiol, Schwerzenbach, Switzerland. [Weickert, Cyndi Shannon] Univ New S Wales, Prince Wales Res Inst, Schizophrenia Res Lab, Randwick, NSW, Australia. RP Harrison, PJ (reprint author), Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England. EM paul.harrison@psych.ox.ac.uk RI Shannon Weickert, Cynthia/G-3171-2011; Law, Amanda/G-6372-2012; OI Law, Amanda/0000-0002-2574-1564 FU Wellcome Trust [068856]; National Science Foundation, Switzerland [3167791.02]; National Center for Competence in Research: Swiss Etiological Study of Adjustment and Mental Health [51A240-104890] FX The study was funded by the Wellcome Trust (grant no. 068856), and the National Science Foundation, Switzerland (Project grant no. 3167791.02) and National Center for Competence in Research: Swiss Etiological Study of Adjustment and Mental Health (grant no. 51A240-104890). We thank Phil Burnet, Andrea Dettling and Sharon Eastwood for their contributions and Phil Cowen for helpful comments on the paper. Valerie West kindly prepared the reference list. NR 128 TC 31 Z9 32 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1381 EP 1394 DI 10.1038/npp.2008.106 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000003 PM 18615010 ER PT J AU Zhou, R Yuan, P Wang, Y Hunsberger, JG Elkahloun, A Wei, Y Damschroder-Williams, P Du, J Chen, G Manji, HK AF Zhou, Rulun Yuan, Peixiong Wang, Yun Hunsberger, Joshua G. Elkahloun, Abdel Wei, Yanling Damschroder-Williams, Patricia Du, Jing Chen, Guang Manji, Husseini K. TI Evidence for Selective microRNAs and Their Effectors as Common Long-Term Targets for the Actions of Mood Stabilizers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE microRNA; lithium; valproate; metabotropic glutamate receptor 7; dipeptidyl-peptidase 10; bipolar disorder ID PROTEIN-KINASE-C; RAT DENTATE GYRUS; BIPOLAR DISORDER; NEUROTROPHIC FACTOR; LITHIUM TREATMENT; IN-VITRO; HIPPOCAMPAL NEUROGENESIS; SIGNALING PATHWAY; ANIMAL-MODEL; VALPROATE AB MicroRNAs (miRNAs) regulate messenger RNA (mRNA) translation in a sequence-specific manner and are emerging as critical regulators of central nervous system plasticity. We found hippocampal miRNA level changes following chronic treatment with mood stabilizers (lithium and valproate (VPA)). Several of these miRNAs were then confirmed by quantitative PCR: let-7b, let-7c, miR-128a, miR-24a, miR-30c, miR-34a, miR-221, and miR-144. The predicted effectors of these miRNAs are involved in neurite outgrowth, neurogenesis, and signaling of PTEN, ERK, and Wnt/beta-catenin pathways. Interestingly, several of these effector-coding genes are also genetic risk candidates for bipolar disorder. We provide evidence that treatment with mood stabilizers increases these potential susceptibility genes in vivo: dipeptidyl-peptidase 10, metabotropic glutamate receptor 7 (GRM7), and thyroid hormone receptor, beta. Treatment of primary cultures with lithium- or VPA-lowered levels of miR-34a and elevated levels of GRM7, a predicted effector of miR-34a. Conversely, miR-34a precursor treatment lowered GRM7 levels and treatment with a miR-34a inhibitor enhanced GRM7 levels. These data confirm that endogenous miR-34a regulates GRM7 levels and supports the notion that miR-34a contributes to the effects of lithium and VPA on GRM7. These findings are the first to demonstrate that miRNAs and their predicted effectors are targets for the action of psychotherapeutic drugs. C1 [Zhou, Rulun; Yuan, Peixiong; Wang, Yun; Hunsberger, Joshua G.; Wei, Yanling; Damschroder-Williams, Patricia; Du, Jing; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. [Elkahloun, Abdel] NHGRI, Microarray CORE Facil, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, Bldg 35,Room 1C-912,35 Convent Dr MSC-3711, Bethesda, MD 20892 USA. EM manjih@mail.nih.gov RI Du, Jing/A-9023-2012; Chen, Guang/A-2570-2017 FU NIMH-NIH FX We thank Ioline Henter for providing outstanding editorial assistance. This work was supported by the Intramural Program of the NIMH-NIH. NR 54 TC 163 Z9 178 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1395 EP 1405 DI 10.1038/npp.2008.131 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000004 PM 18704095 ER PT J AU Gremel, CM Cunningham, CL AF Gremel, Christina M. Cunningham, Christopher L. TI Involvement of Amygdala Dopamine and Nucleus Accumbens NMDA Receptors in Ethanol-Seeking Behavior in Mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ethanol; conditioned place preference; basolateral amygdala; nucleus accumbens; NMDA receptor; dopamine receptor ID CONDITIONED PLACE PREFERENCE; PAVLOVIAN APPROACH BEHAVIOR; MEDIAL PREFRONTAL CORTEX; VENTRAL TEGMENTAL AREA; BASOLATERAL AMYGDALA; DEPENDENT RATS; GLUTAMATE RECEPTORS; EXCITOTOXIC LESIONS; MEASURING REWARD; DRUG-ADDICTION AB Although progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens core. However, specific mechanisms within these nuclei are unknown. In the present experiments, we used site-specific microinfusions of dopamine and NMDA receptor antagonists to examine the roles of accumbens and amygdala in the expression of ethanol conditioned place preference (CPP) in mice. In experiments 1 and 2, a D1/D2/D3 receptor antagonist (flupenthixol) was infused into accumbens or amygdala before testing, whereas experiment 3 used pretest infusions of an NMDA antagonist (AP-5) to examine the role of intra-accumbens NMDA receptors. Dopamine antagonism of accumbens was without effect, but intra-amygdala infusions of flupenthixol blocked CPP expression. Moreover, this effect was dependent upon dopamine antagonism within the basolateral nucleus but not the central nucleus of the amygdala. Antagonism of NMDA receptors in accumbens also blocked CPP expression. The present findings suggest that expression of the ethanol-conditioned response depends upon amygdala dopamine and accumbens NMDA receptors. These are the first studies in any species to show a role for amygdala dopamine receptors and the first studies in mice to implicate accumbens NMDA receptors in ethanol-induced conditioned effects. C1 [Gremel, Christina M.; Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR 97201 USA. RP Gremel, CM (reprint author), NIAAA, Sect Vivo Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room TS-20, Rockville, MD 20852 USA. EM gremelc@mail.nih.gov FU NIH-NIAAA [AA016041, AA007468, AA007702] FX This research was supported by NIH-NIAAA grants AA016041, AA007468, and AA007702. We thank Peter Groblewski and Charlene Voorhees for comments on an earlier draft of this paper. Experiments within this paper comply with the current laws of the United States of America. NR 68 TC 32 Z9 32 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1443 EP 1453 DI 10.1038/npp.2008.179 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000008 PM 18830237 ER PT J AU Chen, YC Holmes, A AF Chen, Yi-Chyan Holmes, Andrew TI Effects of Topiramate and Other Anti-Glutamatergic Drugs on the Acute Intoxicating Actions of Ethanol in Mice: Modulation by Genetic Strain and Stress SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE alcohol; glutamate; NMDA; AMPA; alcoholism; treatment ID CONDITIONED PLACE PREFERENCE; RANDOMIZED CONTROLLED-TRIAL; CULTURED HIPPOCAMPAL-NEURONS; HANDLING-INDUCED CONVULSIONS; ALCOHOL-DEPENDENT PATIENTS; NMDA RECEPTOR ANTAGONIST; D-ASPARTATE RECEPTORS; CHRONIC SWIM STRESS; C57BL/6J MICE; PREPULSE INHIBITION AB Compounds with anti-glutamatergic properties currently in clinical use for various indications (eg Alzheimer's disease, epilepsy, psychosis, mood disorders) have potential utility as novel treatments for alcoholism. Enhanced sensitivity to certain acute intoxicating effects (ataxia, sedative) of alcohol may be one mechanism by which anti-glutamatergic drugs modulate alcohol use. We examined the effects of six compounds (memantine, dextromethorphan, haloperidol, lamotrigine, oxcarbazepine, and topiramate) on sensitivity to acute intoxicating effects of ethanol (ataxia, hypothermia, sedation/hypnosis) in C57BL/6J mice. Analysis of topiramate was extended to determine the influence of genetic background (by comparison of the 129S1, BALB/cJ, C57BL/6J, DBA/2J inbred strains) and prior stress history (by chronic exposure of C57BL/6J to swim stress) on topiramate's effects on ethanol-induced sedation/hypnosis. Results showed that one N-methyl-D-aspartate receptor (NMDAR) antagonist, memantine, but not another, dextromethorphan, potentiated the ataxic but not hypothermic or sedative/hypnotic effects of ethanol. Haloperidol increased ethanol-induced ataxia and sedation/hypnosis to a similar extent as the prototypical NMDAR antagonist MK-801. Of the anticonvulsants tested, lamotrigine accentuated ethanol-induced sedation/hypnosis, whereas oxcarbazepine was without effect. Topiramate was without effect per se under baseline conditions in C57BL/6J, but had a synergistic effect with MK-801 on ethanol-induced sedation/hypnosis. Comparing inbred strains, topiramate was found to significantly potentiate ethanol's sedative/hypnotic effects in BALB/cJ, but not 129S1, C57BL/6J, or DBA/2J strains. Topiramate also increased ethanol-induced sedation/hypnosis in C57BL/6J after exposure to chronic stress exposure. Current data demonstrate that with the exception of MK-801 and haloperidol, the compounds tested had either no significant or assay-selective effects on sensitivity to acute ethanol under baseline conditions in C57BL/6J. However, significant effects of topiramate were revealed as a function of co-treatment with an NMDAR blocker, genetic background, or prior stress history. These findings raise the possibility that topiramate and possibly other anti-glutamatergic drugs could promote the acute intoxicating effects of ethanol in specific subpopulations defined by genetics or life history. C1 [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. [Chen, Yi-Chyan] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov FU National Institute of Alcohol Abuse and Alcoholism Intramural Research Program [Z01-AA000411] FX We thank Marguerite Camp for a critical reading of an earlier version of the paper. This research was supported by the National Institute of Alcohol Abuse and Alcoholism Intramural Research Program (Z01-AA000411). NR 110 TC 13 Z9 14 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1454 EP 1466 DI 10.1038/npp.2008.182 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000009 PM 18843265 ER PT J AU Sabino, V Cottone, P Zhao, Y Iyer, MR Steardo, L Steardo, L Rice, KC Conti, B Koob, GF Zorrilla, EP AF Sabino, Valentina Cottone, Pietro Zhao, Yu Iyer, Malliga R. Steardo, Luca, Jr. Steardo, Luca Rice, Kenner C. Conti, Bruno Koob, George F. Zorrilla, Eric P. TI The sigma-Receptor Antagonist BD-1063 Decreases Ethanol Intake and Reinforcement in Animal Models of Excessive Drinking SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE sigma receptor antagonist; alcohol or ethanol; abstinence or withdrawal; dependence or addiction or alcoholism; self-administration; Sardinian alcohol-preferring rats ID ALCOHOL-PREFERRING RATS; REPEATED METHAMPHETAMINE-TREATMENT; INDUCED BEHAVIORAL SENSITIZATION; CONDITIONED PLACE PREFERENCE; PHEOCHROMOCYTOMA PC12 CELLS; MIDBRAIN DOPAMINE NEURONS; BINDING-SITES; SIGMA(1)-BINDING SITE; MOLECULAR-CLONING; NUCLEUS-ACCUMBENS AB sigma-Receptors (SigRs) have been implicated in behavioral and appetitive effects of psychostimulants and may also modulate the motivating properties of ethanol. This study tested the hypothesis that SigRs modulate ethanol reinforcement and contribute to excessive ethanol intake. The effects of subcutaneous treatment with the potent, selective Sig-1R antagonist BD-1063 on operant ethanol self-administration were studied in two models of excessive drinking-Sardinian alcohol-preferring (sP) rats and acutely withdrawn ethanol-dependent Wistar rats-and compared to ethanol self-administration in nondependent Wistar controls. To assess the specificity of action, the effects of BD-1063 on self-administration of an equally reinforcing saccharin solution were determined in Wistar and sP rats. Gene expression of Sig-1R in reward-related brain areas implicated in ethanol reinforcement was compared between ethanol-naive sP and Wistar rats and withdrawn ethanol-dependent Wistar rats. BD-1063 dose dependently reduced ethanol self-administration in sP rats (3.3-11 mg/kg) and withdrawn, dependent Wistar rats (4-11 mg/kg) at doses that did not modify mean ethanol self-administration in nondependent Wistar controls. BD-1063 did not reduce concurrent water self-administration and did not comparably suppress saccharin self-administration, suggesting selectivity of action. BD-1063 also reduced the breakpoints of sP rats to work for ethanol under a progressive-ratio reinforcement schedule. Ethanol-naive sP rats and 24-h withdrawn, dependent Wistar rats showed reduced Sig-1R mRNA expression in the nucleus accumbens. The results suggest that SigR systems may contribute to innate or ethanol-induced increases in susceptibility to self-administer high ethanol levels, identifying a potential neuroadaptive mechanism contributing to excessive drinking and a therapeutic target for alcohol abuse and dependence. C1 [Sabino, Valentina; Cottone, Pietro; Zhao, Yu; Koob, George F.; Zorrilla, Eric P.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Sabino, Valentina; Cottone, Pietro; Conti, Bruno; Zorrilla, Eric P.] Scripps Res Inst, Harold L Dorris Neurol Res Inst, La Jolla, CA 92037 USA. [Iyer, Malliga R.; Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA. [Iyer, Malliga R.; Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA. [Steardo, Luca, Jr.] Univ Naples SUN, Dept Psychiat, Naples, Italy. [Steardo, Luca] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, Italy. [Conti, Bruno] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. RP Sabino, V (reprint author), Scripps Res Inst, Comm Neurobiol Addict Disorders, SP30-2400,10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM vsabino@scripps.edu; ezorrilla@scripps.edu RI Cottone, Pietro/F-5291-2012; Sabino, Valentina/F-5290-2012; koob, george/P-8791-2016 OI Cottone, Pietro/0000-0003-1320-1672; Sabino, Valentina/0000-0002-6680-1279; FU National Institute on Alcohol Abuse and Alcoholism [AA016731-01, AA012602, 2P60AA006420-25]; Pearson Center for Alcoholism and Addiction Research; NIH Intramural Research Programs of the National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; National Institute on Diabetes and Digestive and Kidney Diseases FX Research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (AA016731-01, AA012602 and 2P60AA006420-25), by the Pearson Center for Alcoholism and Addiction Research, and by the NIH Intramural Research Programs of the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, and the National Institute on Diabetes and Digestive and Kidney Diseases. This is article number 19646 from The Scripps Research Institute. We thank the excellent technical assistance of Molly Brennan, Jeanette Helfers, and Robert Lintz, and the editorial assistance of Mike Arends. NR 93 TC 30 Z9 31 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1482 EP 1493 DI 10.1038/npp.2008.192 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000011 PM 18946467 ER PT J AU Waltz, JA Schweitzer, JB Gold, JM Kurup, PK Ross, TJ Salmeron, BJ Rose, EJ McClure, SM Stein, EA AF Waltz, James A. Schweitzer, Julie B. Gold, James M. Kurup, Pradeep K. Ross, Thomas J. Salmeron, Betty Jo Rose, Emma Jane McClure, Samuel M. Stein, Elliot A. TI Patients with Schizophrenia have a Reduced Neural Response to Both Unpredictable and Predictable Primary Reinforcers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; dopamine; reinforcement; basal ganglia; temporal difference error ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL REWARD PREDICTION; SYSTEM ACTIVATION; RATING-SCALE; DYSFUNCTION; DOPAMINE; ANHEDONIA; FMRI; ABNORMALITIES; NEUROLEPTICS AB One prevalent theory of learning states that dopamine neurons signal mismatches between expected and actual outcomes, called temporal difference errors (TDEs). Evidence indicates that dopamine system dysfunction is involved in negative symptoms of schizophrenia (SZ), including avolition and anhedonia. As such, we predicted that brain responses to TDEs in dopamine midbrain nuclei and target areas would be abnormal in SZ. A total of 18 clinically stable patients with chronic SZ and 18 controls participated in an fMRI study, which used a passive conditioning task. In the task, the delivery of a small amount of juice followed a light stimulus by exactly 6 s on approximately 75% of 78 total trials, and was further delayed by 4-7 s on the remaining trials. The delayed juice delivery was designed to elicit the two types of TDE signals, associated with the recognition that a reward was omitted at the expected time, and delivered at an unexpected time. Main effects of TDE valence and group differences in the positive-negative TDE contrast (unexpected juice deliveries juice omissions) were assessed through whole-brain and regions of interest (ROI) analyses. Main effects of TDE valence were observed for the entire sample in the midbrain, left putamen, left cerebellum, and primary gustatory cortex, bilaterally. Whole-brain analyses revealed group differences in the positive-negative TDE contrast in the right putamen and left precentral gyrus, whereas ROI analyses revealed additional group differences in the midbrain, insula, and parietal operculum, on the right, the putamen and cerebellum, on the left, and the frontal operculum, bilaterally. Further, these group differences were generally driven by attenuated responses in patients to positive TDEs (unexpected juice deliveries), whereas responses to negative TDEs (unexpected juice omissions) were largely intact. Patients also showed reductions in responses to juice deliveries on standard trials, and more blunted reinforcer responses in the left putamen corresponded to higher ratings of avolition. These results provide evidence that SZ patients show abnormal brain responses associated with the processing of a primary reinforcer, which may be a source of motivational deficits. C1 [Waltz, James A.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA. [Schweitzer, Julie B.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Kurup, Pradeep K.; Ross, Thomas J.; Salmeron, Betty Jo; Rose, Emma Jane; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Baltimore, MD USA. [McClure, Samuel M.] Stanford Univ, Dept Psychol, Palo Alto, CA 94304 USA. RP Waltz, JA (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, POB 21247, Baltimore, MD 21228 USA. EM jwaltz@mprc.umaryland.edu RI Ross, Thomas/B-7469-2008; Rose, Emma/A-9960-2010; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Rose, Emma/0000-0001-5365-4794; Salmeron, Betty Jo/0000-0003-1699-9333 FU Intramural NIH HHS [Z99 DA999999]; NCRR NIH HHS [1 K12 RR023250-01, K12 RR023250]; NIMH NIH HHS [1 R24 MH72647-01A1, P30 MH068580, P30 MH068580-01, R24 MH072647] NR 66 TC 88 Z9 88 U1 6 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1567 EP 1577 DI 10.1038/npp.2008.214 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000019 PM 19052540 ER PT J AU Karlsson, RM Tanaka, K Saksida, LM Bussey, TJ Heilig, M Holmes, A AF Karlsson, Rose-Marie Tanaka, Kohichi Saksida, Lisa M. Bussey, Timothy J. Heilig, Markus Holmes, Andrew TI Assessment of Glutamate Transporter GLAST (EAAT1)-Deficient Mice for Phenotypes Relevant to the Negative and Executive/Cognitive Symptoms of Schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE glutamate; schizophrenia; cognition; prepulse inhibition; social withdrawal; anhedonia ID NMDA RECEPTOR HYPOFUNCTION; REPEATED MATERNAL SEPARATION; PREFRONTAL CORTEX; COGNITIVE NEUROSCIENCE; BEHAVIORAL PHENOTYPES; PREPULSE INHIBITION; GLIAL GLUTAMATE; KNOCKOUT MICE; MOUSE STRAINS; MUTANT MICE AB Glutamatergic dysfunction is increasingly implicated in the pathophysiology of schizophrenia. Current models postulate that dysfunction of glutamate and its receptors underlie many of the symptoms in this disease. However, the mechanisms involved are not well understood. Although elucidating the role for glutamate transporters in the disease has been limited by the absence of pharmacological tools that selectively target the transporter, we recently showed that glial glutamate and aspartate transporter (GLAST; excitatory amino-acid transporter 1) mutant mice exhibit abnormalities on behavioral measures thought to model the positive symptoms of schizophrenia, some of which were rescued by treatment with either haloperidol or the mGlu2/3 agonist, LY379268 the mGlu2/3 agonist, LY379268. To further determine the role of GLAST in schizophrenia-related behaviors we tested GLAST mutant mice on a series of behavioral paradigms associated with the negative (social withdrawal, anhedonia), sensorimotor gating (prepulse inhibition of startle), and executive/cognitive (discrimination learning, extinction) symptoms of schizophrenia. GLAST knockout (KO) mice showed poor nesting behavior and abnormal sociability, whereas KO and heterozygous (HET) both demonstrated lesser preference for a novel social stimulus compared to wild-type littermate controls. GLAST KO, but not HET, had a significantly reduced acoustic startle response, but no significant deficit in prepulse inhibition of startle. GLAST KO and HET showed normal sucrose preference. In an instrumental visual discrimination task, KO showed impaired learning. By contrast, acquisition and extinction of a simple instrumental response was normal. The mGlu2/3 agonist, LY379268, failed to rescue the discrimination impairment in KO mice. These findings demonstrate that gene deletion of GLAST produces select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. C1 [Karlsson, Rose-Marie; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Karlsson, Rose-Marie; Heilig, Markus] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Tanaka, Kohichi] Tokyo Med & Dent Univ, Sch Biomed Sci, Lab Mol Neurosci, Tokyo, Japan. [Tanaka, Kohichi] Tokyo Med & Dent Univ, Med Res Inst, Tokyo, Japan. [Saksida, Lisa M.; Bussey, Timothy J.] Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. [Saksida, Lisa M.; Bussey, Timothy J.] MRC, Cambridge, England. [Saksida, Lisa M.; Bussey, Timothy J.] Wellcome Trust Behav & Clin Neurosci Inst, Cambridge, England. [Holmes, Andrew] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. RP Karlsson, RM (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10 Room IE-5330, Bethesda, MD 20892 USA. EM karlssonr@mail.nih.gov RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Heilig, Markus/0000-0003-2706-2482 FU National Institute on Alcohol Abuse and Alcoholism Intramural Research Program; The Novartis Foundation (Japan); The Tokyo Biochemical Research Foundation; Research Foundation for Opto-Science and Technology [20022013, 18053006]; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX We thank Dr Jeffrey Rothstein at the John Hopkins University for providing mutant mice for breeding, Dr Judith Davis and Monique Melige for assistance with breeding, and Ben Palachick and Jessica Ihne for technical assistance. We are also thankful to Gene S Fisch for expert statistical advice. This work was supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program. TK was supported by The Novartis Foundation (Japan) for the promotion of Science, Takeda Science Foundation, The Tokyo Biochemical Research Foundation, Research Foundation for Opto-Science and Technology, and by grants-in-aids for Scientific Research on Priority Area (20022013 and 18053006) provided by the Ministry of Education, Culture, Sports, Science, and Technology of Japan. NR 66 TC 74 Z9 75 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1578 EP 1589 DI 10.1038/npp.2008.215 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000020 PM 19078949 ER PT J AU Sun, YH Zupan, B Raaka, BM Toth, M Gershengorn, MC AF Sun, Yuhua Zupan, Bojana Raaka, Bruce M. Toth, Miklos Gershengorn, Marvin C. TI TRH-Receptor-Type-2-Deficient Mice are Euthyroid and Exhibit Increased Depression and Reduced Anxiety Phenotypes SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE thyrotropin-releasing hormone; thyrotropin-releasing hormone receptors; depression; anxiety; behavioral changes; TRH-R2-deficient mouse ID RECEPTOR 1-DEFICIENT MICE; BETA-CELL LINES; HORMONE-RECEPTOR; MOLECULAR-CLONING; RAT-BRAIN; SEROTONIN(1A) RECEPTOR; FUNCTIONAL EXPRESSION; MAJOR DEPRESSION; ANIMAL-MODELS; TRH RECEPTOR AB Thyrotropin-releasing hormone (TRH) is a neuropeptide that initiates its effects in mice by interacting with two G-protein-coupled receptors, TRH receptor type 1 (TRH-R1) and TRH receptor type 2 (TRH-R2). Two previous reports described the effects of deleting TRH-R1 in mice. TRH-R1 knockout mice exhibit hypothyroidism, hyperglycemia, and increased depression and anxiety-like behavior. Here we report the generation of TRH-R2 knockout mice. The phenotype of these mice was characterized using gross and histological analyses along with blood hematological assays and chemistries. Standard metabolic tests to assess glucose and insulin tolerance were performed. Behavioral testing included elevated plus maze, open field, tail suspension, forced swim, and novelty-induced hypophagia tests. TRH-R2 knockout mice are euthyroid with normal basal and TRH-stimulated serum levels of thyroid-stimulating hormone (thyrotropin), are normoglycemic, and exhibit normal development and growth. Female, but not male, TRH-R2 knockout mice exhibit moderately increased depression-like and reduced anxiety-like phenotypes. Because the behavioral changes in TRH-R1 knockout mice may have been caused secondarily by their hypothyroidism whereas TRH-R2 knockout mice are euthyroid, these data provide the first evidence for the involvement of the TRH/TRH-R system, specifically extrahypothalamic TRH/TRH-R2, in regulating mood and affect. C1 [Sun, Yuhua; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Zupan, Bojana; Toth, Miklos] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 50 S Dr,Room 4134, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov FU Intramural Research Program; NIDDK; NIH [5R01 MH058669, 1RO1 MH080194]; NIH predoctoral training [5T32DA007274] FX We thank Dr Chuxia Deng, NIDDK Core Knockout Laboratory for advice and help in creating TRH- R2deficient mice. We also thank Dr Oksana Gavrilova, NIDDK Mouse Metabolism Core Laboratory, for advice and help with analysis of growth and glucose/insulin homeostasis in TRH-R2-deficient mice. This work was supported by the Intramural Research Program, NIDDK, NIH and grants 5R01 MH058669 and 1RO1 MH080194 to MT. BZ was supported by NIH predoctoral training grant 5T32DA007274. NR 45 TC 20 Z9 20 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAY PY 2009 VL 34 IS 6 BP 1601 EP 1608 DI 10.1038/npp.2008.217 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 433QN UT WOS:000265221000022 PM 19078951 ER PT J AU Savitz, J Drevets, WC AF Savitz, Jonathan Drevets, Wayne C. TI Bipolar and major depressive disorder: Neuroimaging the develop mental-degenerative divide SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE Bipolar disorder; Major depressive disorder; Neuroimaging; MRI; PET; Amygdala; Hippocampus; Basal ganglia; Orbitofrontal cortex; Subgenual anterior cingulate; Dorsolateral prefrontal cortex; Genetics ID WHITE-MATTER HYPERINTENSITIES; FUNCTIONAL MAGNETIC-RESONANCE; VOXEL-BASED MORPHOMETRY; LATE-LIFE DEPRESSION; SUBGENUAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; CEREBRAL GLUCOSE-METABOLISM; POSTTRAUMATIC-STRESS-DISORDER; REDUCED HIPPOCAMPAL VOLUME AB Both major depressive disorder and bipolar disorder are the subject of a voluminous imaging and genetics literature. Here, we attempt a comprehensive review of MRI and metabolic PET studies conducted to date on these two disorders, and interpret our findings from the perspective of developmental and degenerative models of illness. Elevated activity and volume loss of the hippocampus, orbital and ventral prefrontal cortex are recurrent themes in the literature. In contrast, dorsal aspects of the PFC tend to display hypometabolism. Ventriculomegaly and white matter hyperintensities are intimately associated with depression in elderly populations and likely have a vascular origin. Important confounding influences are medication, phenotypic and genetic heterogeneity, and technological limitations. We suggest that environmental stress and genetic risk variants interact with each other in a complex manner to alter neural circuitry and precipitate illness. Imaging genetic approaches hold out promise for advancing our understanding of affective illness. Published by Elsevier Ltd C1 [Savitz, Jonathan; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Savitz, J (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. EM savitzj@mail.nih.gov RI Savitz, Jonathan/C-3088-2009 OI Savitz, Jonathan/0000-0001-8143-182X FU Intramural NIH HHS [Z99 MH999999] NR 595 TC 230 Z9 238 U1 18 U2 55 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD MAY PY 2009 VL 33 IS 5 BP 699 EP 771 DI 10.1016/j.neubiorev.2009.01.004 PG 73 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 449BE UT WOS:000266305000008 PM 19428491 ER PT J AU Hikosaka, O AF Hikosaka, Okihide TI Obituary: Dr. Ichiji Tasaki SO NEUROSCIENCE RESEARCH LA English DT Biographical-Item C1 NIH, NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NIH, NEI, Sensorimotor Res Lab, 49 Convent Dr,Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov NR 1 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD MAY PY 2009 VL 64 IS 1 BP 1 EP 2 DI 10.1016/j.neures.2009.03.001 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 447KX UT WOS:000266191100001 ER PT J AU Harvey, BK Chou, J Shen, H Hoffer, BJ Wang, Y AF Harvey, Brandon K. Chou, Jenny Shen, Hui Hoffer, Barry J. Wang, Yun TI Diadenosine tetraphosphate reduces toxicity caused by high-dose methamphetamine administration SO NEUROTOXICOLOGY LA English DT Article DE Diadenosine tetraphosphate; Methamphetamine; Apoptosis; Neuroprotection; Dopamine ID AMPHETAMINE-INDUCED RELEASE; NIGRA PARS RETICULATA; NEURONAL APOPTOSIS; ENVIRONMENTAL-TEMPERATURE; CONSCIOUS RAT; DEATH PATHWAY; POLYPHOSPHATES; DOPAMINE; RECEPTOR; BRAIN AB Diadenosine tetraphosphate (AP(4)A), two adenosine moieties bridged by four phosphates, is an endogenous purinergic ligand found in brain. Previous studies have shown that ANA reduced neurodegeneration caused by the dopaminergic neurotoxin 6-hydroxydopamine in rat striatum and substantia nigra. The purpose of this study was to determine whether AP4A is protective against methamphetamine (MA)-mediated toxicity. Primary neuronal cultures were prepared from rat embryonic (E14-E15) ventral mesencephalic tissue. Cultures treated with 2 mM MA exhibited decreased tyrosine hydroxylase (TH) immunoreactivity and increased cleaved caspase-3 immunoreactivity and TUNEL labeling. All these changes were lessened by pretreatment with AP(4)A. The protective effect of AP(4)A was also found in vivo. Adult Sprague-Dawley rats were injected with AP(4)A (25 mu g/20 mu l) or vehicle intracerebroventricularly followed by 4 doses of MA (5 or 10 mg/kg), given subcutaneously every 2 h. Administration of MA reduced locomotor activity 1 day after injection, which was significantly antagonized by the pretreatment with AP(4)A. Using immunohistochemical analysis, TH fiber density at the substantia nigra pars reticulata was found reduced while cleaved caspase-3 immunoreactivity in striatum was increased after MA treatment; these responses were also significantly antagonized by AP(4)A. Taken together, our data show that AP(4)A has protective effects against MA-mediated toxicity both in vitro and in vivo. The mechanism of action involves suppression of MA-induced apoptosis. Published by Elsevier Inc. C1 [Harvey, Brandon K.; Chou, Jenny; Shen, Hui; Hoffer, Barry J.; Wang, Yun] Natl Inst Drug Abuse, IRP Neural Protect & Regenerat Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Wang, Y (reprint author), Natl Inst Drug Abuse, IRP Neural Protect & Regenerat Sect, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM ywang@intra.nida.nih.gov FU Intramural Research Program at the National Institute on Drug Abuse; National Institutes of Health FX This work was supported by the Intramural Research Program at the National Institute on Drug Abuse, National Institutes of Health. The authors would like to thank Dr. Jean Lud Cadet for his comments and Ms. Kathleen Powers for her technical assistance. NR 28 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2009 VL 30 IS 3 BP 436 EP 444 DI 10.1016/j.neuro.2009.02.003 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 448RH UT WOS:000266279200014 PM 19442829 ER PT J AU Ferguson, SA Delclos, KB Newbold, RR Flynn, KM AF Ferguson, Sherry A. Delclos, K. Barry Newbold, Retha R. Flynn, Katherine M. TI Few effects of multi-generational dietary exposure to genistein or nonylphenol on sodium solution intake in male and female Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Genistein; Nonylphenol; Sodium; Endocrine disrupter; Rat ID ADULT-ONSET DISEASE; ENDOCRINE DISRUPTOR VINCLOZOLIN; SEXUALLY DIMORPHIC BEHAVIORS; INFLUENCING SALT APPETITE; SEX-DIFFERENCES; MULTIGENERATIONAL EXPOSURE; REPRODUCTIVE-SYSTEM; OFFSPRING TOXICITY; NACL INTAKE; PREFERENCE AB Previous work in our laboratory indicated that lifelong dietary exposure to estrogen-like endocrine disrupters; increased sodium solution intake in adult male and female rats. Here, we sought to discern the critical periods necessary for this alteration as well as establish the effects of lower dietary concentrations of genistein and nonylphenol. Male and female Sprague-Dawley rats (F0) consumed phytoestrogen-free chow containing 0, 5, 100, or 500 ppm genistein (approximate to 0.0, 0.4, 8.0, and 40.0 mg/kg/day) or 0, 25, 200, or 750 ppm nonylphenol (approximate to 0.0, 2.0,16.0, and 60.0 mg/kg/day). Rats were mated within treatment groups and offspring (F1) maintained on the same diets. Mating for the F1, F2, and F3 (genistein only) was within treatment groups. At postnatal day (PND) 21, the F3 generation began to consume unadulterated phytoestrogen-free chow such that genistein exposure occurred only in utero and preweaning. The F4 generation was never directly exposed to genistein. On PNDs 65-68, intake of regular water and a 3.0% sodium chloride solution was measured for F1-F4 generations (genistein portion) or F1-F2 (nonylphenol portion). Although body weights were decreased by the highest dietary concentrations of genistein and nonylphenol, there were only minimal effects of exposure on sodium solution intake. As expected, intake was highest in female rats. With previous data, these results indicate that the dietary concentrations necessary to increase adult sodium solution intake in rats are greater than 500 ppm genistein and 750 ppm nonylphenol and such effects do not appear to increase across generations. Published by Elsevier Inc. C1 [Ferguson, Sherry A.; Flynn, Katherine M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Delclos, K. Barry] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Newbold, Retha R.] NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU U.S. Food and Drug Administration [IAG 224-07-007]; National Institute for Environmental Health Sciences; Oak Ridge Institute for Science Education FX This work was supported by Interagency Agreement IAG 224-07-007 between the U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences. The extensive and expert technical assistance of the NCTR support staff in providing diet preparation, chemical analysis, and computer support services for these studies is gratefully acknowledged. The authors would like to express their appreciation to the animal care technicians of the Bionetics Corporation for their excellent technical expertise and Erika Gray for her skillful data summaries. In particular, grateful appreciation is extended to Connie Weis for her organization in these studies. Katherine Flynn was supported by a post-doctoral fellowship from the Oak Ridge Institute for Science Education. NR 45 TC 8 Z9 8 U1 3 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2009 VL 31 IS 3 BP 143 EP 148 DI 10.1016/j.ntt.2009.01.009 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 449CZ UT WOS:000266309700001 PM 19452615 ER PT J AU Paz, MS Smith, LM LaGasse, LL Derauf, C Grant, P Shah, R Arria, A Huestis, M Haning, W Strauss, A Della Grotta, S Liu, J Lester, BM AF Paz, Monica S. Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Grant, Penny Shah, Rizwan Arria, Amelia Huestis, Marilyn Haning, William Strauss, Arthur Della Grotta, Sheri Liu, Jing Lester, Barry M. TI Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Prenatal exposure; Neurodevelopment; Drugs; Depression ID LIFE-STYLE; PSYCHIATRIC-SYMPTOMS; SUBSTANCE EXPOSURE; INFANT DEVELOPMENT; SOCIAL SUPPORT; FETAL-GROWTH; PREGNANCY; POSTPARTUM; PREVALENCE; WOMEN AB Background: The effects of maternal depression on neonatal neurodevelopment in MA exposed neonates have not been well characterized. Objective: To determine the neurobehavioral effects of maternal depressive symptoms oil neonates exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). Design: The purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome. IDEAL screened 13,808 subjects, 1632 were eligible and consented and 176 mothers were enrolled. Only biological mothers with Custody of their child at the one-month visit (n = 50 MA; n = 86 comparison) had the Addiction Severity Index (ASI) administered. The NNNS was administered to the neonate by an examiner blinded to MA exposure within the first five days of life. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS outcomes, with and without covariates. Significance was accepted at p<.05. Results: After adjusting for covariates, regardless of exposure status, maternal depressive symptoms were associated with lower handling and arousal scores, elevated physiological stress scores and an increased incidence of hypotonicity. When adjusting for covariates, MA exposure was associated with lower arousal and higher lethargy scores. Conclusions: Maternal depressive symptoms are associated with neurodevelopmental patterns of decreased arousal and increased stress. Prenatal MA exposure combined with maternal depression was not associated with any additional neonatal neurodevelopmental differences. (C) 2009 Published by Elsevier Inc. C1 [Paz, Monica S.; Smith, Lynne M.] Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Torrance, CA 90502 USA. [Paz, Monica S.; Smith, Lynne M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [LaGasse, Linda L.; Della Grotta, Sheri; Liu, Jing; Lester, Barry M.] Women & Infants Hosp Rhode Isl, Brown Med Sch, Providence, RI USA. [Derauf, Chris; Haning, William] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Grant, Penny] Univ Oklahoma, Norman, OK 73019 USA. [Shah, Rizwan] Blank Childrens Hosp Iowa Hlth, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, College Pk, MD 20742 USA. [Huestis, Marilyn] Natl Inst Drug Abuse, Sect Chem & Drug Metab, Bethesda, MD 20892 USA. [Strauss, Arthur] Long Beach Mem Med Ctr, Long Beach, CA USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,RB 1, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NIDA [1 R01 DA014918]; National Center on Research Resources [3 M01 RR00425, P20 RR11091] FX This study was supported by NIDA Grant# 1 R01 DA014918 and in part by the National Center on Research Resources, Grant # 3 M01 RR00425 and P20 RR11091. NR 60 TC 15 Z9 15 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2009 VL 31 IS 3 BP 177 EP 182 DI 10.1016/j.ntt.2008.11.004 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 449CZ UT WOS:000266309700005 PM 19059478 ER PT J AU Wei, LH Zhang, XL Gallazzi, F Miao, YB Jin, XF Brechbiel, MW Xu, H Clifford, T Welch, MJ Lewis, JS Quinn, TP AF Wei, Lihui Zhang, Xiuli Gallazzi, Fabio Miao, Yubin Jin, Xiaofang Brechbiel, Martin W. Xu, Heng Clifford, Thomas Welch, Michael J. Lewis, Jason S. Quinn, Thomas P. TI Melanoma imaging using In-111-, Y-86- and Ga-68-labeled CHX-A ''-Re(Arg(11))CCMSH SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Melanoma; Imaging; alpha-MSH; Peptide; CHX-A '' ID STIMULATING HORMONE PEPTIDE; TUMOR-TARGETING PROPERTIES; ALPHA-MSH; MALIGNANT-MELANOMA; MELANOCORTIN RECEPTORS; MONOCLONAL-ANTIBODIES; THERAPEUTIC-EFFICACY; CHELATING-AGENT; ANALOG; RHENIUM AB Introduction: A novel alpha-melanocyte-stimulating hormone peptide analog CHX-A"-Re(Arg(11))CCMSH, which targeted the melanocortin-1 receptor (MCI-R) overexpressed on melanoma cells, was investigated for its biodistribution and tumor imaging properties Methods: The metal bifunctional chelator CHX-A '' was conjugated to the melanoma targeting peptide (Arg(11))CCMSH and cyclized by Re incorporation to yield CHX-A ''-Re(Arg(11))CCMSH. CHX-A ''-Re(Arg(11))CCMSH was labeled with In-111, Y-86 and Ga-68, and the radiolabeled peptides were examined in B16/F1 melanoma-bearing mice for their pharmacokinetic as well as their tumor targeting properties using small Results: The radiolabeling efficiencies of the In-111-, Y-86- and Ga-68-labeled CHX-A ''-Re(Arg(11))CCMSH peptides were >95%, resulting in specific activities of 4.44, 3.7 and 1.85 MBq/mu g, respectively. Tumor uptake of the In-111-, Y-86- and Ga-68-labeted peptides was rapid with 4.17 +/- 0.94, 4.68 +/- 1.02 and 2.68 +/- 0.69 %ID/g present in the tumors 2 h postinjection, respectively. Disappearance of radioactivity from the normal organs and tissues was rapid with the exception ofthe kidneys. Melanorna tuniors were iniaged with all three radiolabeled peptides 2 h postinjection. MC1-R-specific uptake was confirmed by competitive receptor blocking studies. Conclusions: Melanoma tumour uptake and imaging was exhibited by the In-111-, Y-86- and Ga-68-labeled Re(Arg(11))CCMSH peptides, although the tumor uptake was moderated by low specific activity. The facile radiolabeling properties of CHX-A ''-Re(Arg(11))CCMSH allow it to be employed as a melanoma imaging agent with little or no purification after In-111, Y-86 and Ga-68 labeling. (C) 2009 Elsevier Inc. All rights reserved. C1 [Zhang, Xiuli; Gallazzi, Fabio; Miao, Yubin; Jin, Xiaofang; Quinn, Thomas P.] Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. [Wei, Lihui; Welch, Michael J.; Lewis, Jason S.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. [Zhang, Xiuli; Miao, Yubin; Quinn, Thomas P.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. [Brechbiel, Martin W.; Xu, Heng; Clifford, Thomas] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20893 USA. RP Quinn, TP (reprint author), Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. EM quinnt@missouri.edu FU National Cancer Institute [P50-103130, R24 CA86307, R90DK071510]; Veterans Administration Hospital Biomolecular Imaging Center, Columbia, MO, USA; NIH/NCI SAIRP [R24 CA86060]; NCI Cancer Center [P30 CA91842]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX The authors would like to acknowledge support from the National Cancer Institute P50-103130, R24 CA86307, the NIH Clinical Biodetective Graduate Training Grant R90DK071510 and the Harry S. Truman Veterans Administration Hospital Biomolecular Imaging Center, Columbia, MO, USA. Small animal PET imaging was supported by an NIH/NCI SAIRP grant (R24 CA86060),with additional support from the Small Animal Imaging Core of the Alvin J. Sitenian Cancer Center at Washington University and Barnes-Jewish Hospital. The SAIC is supported by all NCI Cancer Center Support Grant P30 CA91842. This research was supported in pail by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 40 TC 28 Z9 29 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2009 VL 36 IS 4 BP 345 EP 354 DI 10.1016/j.nucmedbio.2009.01.007 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 446UM UT WOS:000266146700002 PM 19423001 ER PT J AU Ma, Y Lang, LX Reyes, L Tokugawa, J Jagoda, EM Kiesewetter, DO AF Ma, Ying Lang, Lixin Reyes, Larry Tokugawa, Joji Jagoda, Elaine M. Kiesewetter, Dale O. TI Application of highly sensitive UPLC-MS to determine biodistribution at tracer doses: validation with the 5-HT1A ligand [F-18]FPWAY SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE PET radiotracer; Biodistribution; LC/MS; FPWAY; 5-HT1A; Metabolites ID RECEPTOR OCCUPANCY; DOPAMINE D2; PET; WAY-100635; ANTAGONISTS; BRAIN AB High-sensitivity and high-resolution LC/MS instrumentation has been applied in positron emission tomography (PET) radiophrmaceutical development to provide quantitative measurement of the mass of radiotracers extracted from tissues of rats. We employed the highly sensitive Waters Q-TOF premier MS coupled with an Acquity UPLC system to demonstrate that LC-MS call generate ex vivo biodistribution data for PET 5-HT1A ligand FPWAY without the need to radiolabel. For the biodistribution Studies, we injected rats with [F-18] FPWAY containing various amounts of nonradioactive FPWAY. At the end of the allotted time, the animals were killed and six regions of brain and plasma from each animal were processed for quantitative measurement of parent compound concentration by LC-MS. These data were then converted to the differential uptake ratio DUR (%1D/g*body weight/100) and the brain tissue-specific binding ratio to allow direct comparison with data obtained by gamma counting of the coinjected radioactive [F-18]FPWAY. The DUR and the brain tissue-specific binding ratio calculated using the LC-MS method were highly correlated to the values obtained by standard radioactivity measurements of [F-18] FPWAY. In conclusion, there was significant concordance between the LC/MS and radioactivity method in determination of DUR and the specific binding ratio in the rat brain. This concordance indicated that high-sensitivity, LC/MS is an indispensable tool in evaluating the quantity of administered chemical in tissue as part of the development of new molecular imaging probes. Published by Elsevier Inc. C1 [Ma, Ying; Lang, Lixin; Reyes, Larry; Tokugawa, Joji; Jagoda, Elaine M.; Kiesewetter, Dale O.] NIBIB, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA. RP Ma, Y (reprint author), NIBIB, PET Radiochem Grp, NIH, Bethesda, MD 20892 USA. EM ym45J@nih.gov FU Intramural NIH HHS [Z01 EB000001-03] NR 17 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2009 VL 36 IS 4 BP 389 EP 393 DI 10.1016/j.nucmedbio.2009.01.002 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 446UM UT WOS:000266146700007 PM 19423006 ER PT J AU de Silanes, IL Gorospe, M Taniguchi, H Abdelmohsen, K Srikantan, S Alaminos, M Berdasco, M Urdinguio, RG Fraga, MF Jacinto, FV Esteller, M AF Lopez de Silanes, Isabel Gorospe, Myriam Taniguchi, Hiroaki Abdelmohsen, Kotb Srikantan, Subramanya Alaminos, Miguel Berdasco, Mara Urdinguio, Roco G. Fraga, Mario F. Jacinto, Filipe V. Esteller, Manel TI The RNA-binding protein HuR regulates DNA methylation through stabilization of DNMT3b mRNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DE-NOVO METHYLATION; INCREASED CYCLOOXYGENASE-2 EXPRESSION; CYTOPLASMIC HUR; METHYLTRANSFERASE EXPRESSION; TRANSLATIONAL CONTROL; OVARIAN-CARCINOMA; PROGNOSTIC-FACTOR; BREAST-CARCINOMA; NUCLEAR EXPORT; HUMAN-DISEASE AB The molecular basis underlying the aberrant DNA-methylation patterns in human cancer is largely unknown. Altered DNA methyltransferase (DNMT) activity is believed to contribute, as DNMT expression levels increase during tumorigenesis. Here, we present evidence that the expression of DNMT3b is post-transcriptionally regulated by HuR, an RNA-binding protein that stabilizes and/or modulates the translation of target mRNAs. The presence of a putative HuR-recognition motif in the DNMT3b 3UTR prompted studies to investigate if this transcript associated with HuR. The interaction between HuR and DNMT3b mRNA was studied by immunoprecipitation of endogenous HuR ribonucleoprotein complexes followed by RTqPCR detection of DNMT3b mRNA, and by in vitro pulldown of biotinylated DNMT3b RNAs followed by western blotting detection of HuR. These studies revealed that binding of HuR stabilized the DNMT3b mRNA and increased DNMT3b expression. Unexpectedly, cisplatin treatment triggered the dissociation of the [HuR-DNMT3b mRNA] complex, in turn promoting DNMT3b mRNA decay, decreasing DNMT3b abundance, and lowering the methylation of repeated sequences and global DNA methylation. In summary, our data identify DNMT3b mRNA as a novel HuR target, present evidence that HuR affects DNMT3b expression levels post-transcriptionally, and reveal the functional consequences of the HuR-regulated DNMT3b upon DNA methylation patterns. C1 [Lopez de Silanes, Isabel; Taniguchi, Hiroaki; Berdasco, Mara; Urdinguio, Roco G.; Fraga, Mario F.; Jacinto, Filipe V.; Esteller, Manel] Spanish Natl Canc Res Ctr CNIO, Canc Epigenet Lab, Mol Pathol Program, Madrid 28029, Spain. [Gorospe, Myriam; Abdelmohsen, Kotb; Srikantan, Subramanya] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Alaminos, Miguel] Univ Granada, Dept Histol, Granada, Spain. [Alaminos, Miguel] Hosp Clin Fdn, Granada, Spain. [Esteller, Manel] ICREA, Barcelona 08010, Spain. [Esteller, Manel] Inst Invest Biomed Bellvitge IDIBELL, Canc Epigenet & Biol Program PEBC, Catalan Inst Oncol ICO, Barcelona 08907, Catalonia, Spain. RP de Silanes, IL (reprint author), Spanish Natl Canc Res Ctr CNIO, Canc Epigenet Lab, Mol Pathol Program, Madrid 28029, Spain. EM ilsilanes@cnio.es; mesteller@iconcologia.net RI Esteller, Manel/L-5956-2014; ALAMINOS, MIGUEL/N-9960-2016; Lopez de Silanes, Isabel/K-4962-2015; OI Esteller, Manel/0000-0003-4490-6093; ALAMINOS, MIGUEL/0000-0003-4876-2672; Lopez de Silanes, Isabel/0000-0001-6762-9792; srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU CANCERDIP [FP7-200620]; Spanish Ministry of Science and Innovation [PI061653]; National Institute on Aging-IRP, National Institutes of Health; Fondo de Investigaciones Sanitarias (FIS); Spanish Ministry of Science and Innovation; [SAF2007-00027-65134]; [CSD2006-49] FX Grants SAF2007-00027-65134; Consolider CSD2006-49; CANCERDIP FP7-200620; Spanish Ramon & Cajal Programme and the FIS Programme (PI061653) both from the Spanish Ministry of Science and Innovation (to I. L. S.). National Institute on Aging-IRP, National Institutes of Health (to M. G. and K. A.). Funding for open access charge: Fondo de Investigaciones Sanitarias (FIS). Spanish Ministry of Science and Innovation. NR 63 TC 23 Z9 23 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2009 VL 37 IS 8 BP 2658 EP 2671 DI 10.1093/nar/gkp123 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 444AU UT WOS:000265953000030 ER PT J AU Zurla, C Manzo, C Dunlap, D Lewis, DEA Adhya, S Finzi, L AF Zurla, Chiara Manzo, Carlo Dunlap, David Lewis, Dale E. A. Adhya, Sankar Finzi, Laura TI Direct demonstration and quantification of long-range DNA looping by the bacteriophage repressor SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LAMBDA CI REPRESSOR; TETHERED PARTICLE MOTION; GENE-REGULATION; NONSPECIFIC-BINDING; STREPTOCOCCUS-MITIS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; SINGLE-MOLECULE; HUMAN PLATELETS; RIGHT OPERATOR AB Recently, it was proposed that DNA looping by the repressor (CI protein) strengthens repression of lytic genes during lysogeny and simultaneously ensures efficient switching to lysis. To investigate this hypothesis, tethered particle motion experiments were performed and dynamic CI-mediated looping of single DNA molecules containing the repressor binding sites separated by 2317 bp (the wild-type distance) was quantitatively analyzed. DNA containing all three intact operators or with mutated o3 operators were compared. Modeling the thermodynamic data established the free energy of CI octamer-mediated loop formation as 1.7 kcal/mol, which decreased to 0.7 kcal/mol when supplemented by a tetramer (octamertetramer-mediated loop). These results support the idea that loops secured by an octamer of CI bound at oL1, oL2, oR1 and oR2 operators must be augmented by a tetramer of CI bound at the oL3 and oR3 to be spontaneous and stable. Thus the o3 sites are critical for loops secured by the CI protein that attenuate cI expression. C1 [Zurla, Chiara; Manzo, Carlo; Finzi, Laura] Emory Univ, Dept Phys, Atlanta, GA 30322 USA. [Dunlap, David] Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA. [Lewis, Dale E. A.; Adhya, Sankar] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Finzi, L (reprint author), Emory Univ, Dept Phys, 400 Dowman Dr, Atlanta, GA 30322 USA. EM lfinzi@emory.edu RI Manzo, Carlo/B-9745-2012 OI Manzo, Carlo/0000-0002-8625-0996 FU HFSPO [RGP0050/2002-C]; Emory [URC-2006]; National Institutes of Health; National Cancer Institute; Center for Cancer Research FX HFSPO (RGP0050/2002-C to L. F. and S. A.); Emory URC-2006 (to LF); Intramural Research Program of the National Institutes of Health, National Cancer Institute and the Center for Cancer Research (to S. A.). Funding for open access charge: SA's Intramural Research Program of the National Institutes of Health, National Cancer Institute and the Center for Cancer Research. NR 45 TC 39 Z9 39 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2009 VL 37 IS 9 BP 2789 EP 2795 DI 10.1093/nar/gkp134 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 449UB UT WOS:000266354600003 PM 19276206 ER PT J AU Cui, F Zhurkin, VB AF Cui, Feng Zhurkin, Victor B. TI Distinctive sequence patterns in metazoan and yeast nucleosomes: Implications for linker histone binding to AT-rich and methylated DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CORE PARTICLE; CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; CHROMATIN-STRUCTURE; MICROCOCCAL NUCLEASE; ANGSTROM RESOLUTION; HOMOLOG HHO1P; THYMINE DIMER; FINGER DNA AB Linker histones (LHs) bind to the DNA entry/exit points of nucleosomes and demonstrate preference for AT-rich DNA, although the recognized sequence patterns remain unknown. These patterns are expected to be more pronounced in metazoan nucleosomes with abundant LHs, compared to yeast nucleosomes with few LHs. To test this hypothesis, we compared the nucleosome core particle (NCP) sequences from chicken, Drosophila and yeast, extending them by the flanking sequences extracted from the genomes. We found that the known 10-bp periodic oscillation of AT-rich elements goes beyond the ends of yeast nucleosomes, but is distorted in metazoan sequences where the out-of-phase AT-peaks appear at the NCP ends. The observed difference is likely to be associated with sequence-specific LH binding. We therefore propose a new structural model for LH binding to metazoan nucleosomes, postulating that the highly conserved nonpolar wing region of the LH globular domain (tetrapeptide GVGA) recognizes AT-rich fragments through hydrophobic interactions with the thymine methyl groups. These interactions lead to DNA bending at the NCP ends and formation of a stem-like structure. The same mechanism accounts for the high affinity of LH to methylated DNAa feature critical for stabilization of the higher-order structure of chromatin and for repression of transcription. C1 [Cui, Feng; Zhurkin, Victor B.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM zhurkin@nih.gov FU The Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Funding for open access charge: Intramural Research Program of the National Institutes of Health. NR 72 TC 33 Z9 35 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2009 VL 37 IS 9 BP 2818 EP 2829 DI 10.1093/nar/gkp113 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 449UB UT WOS:000266354600006 PM 19282449 ER PT J AU McCulloch, SD Kokoska, RJ Garg, P Burgers, PM Kunkel, TA AF McCulloch, Scott D. Kokoska, Robert J. Garg, Parie Burgers, Peter M. Kunkel, Thomas A. TI The efficiency and fidelity of 8-oxo-guanine bypass by DNA polymerases and SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STATE KINETIC-ANALYSIS; ESCHERICHIA-COLI DINB; THYMINE DIMER BYPASS; PRONE LESION BYPASS; ERROR-FREE BYPASS; ETA IN-VIVO; SACCHAROMYCES-CEREVISIAE; STEADY-STATE; HUMAN-CELLS; TRANSLESION SYNTHESIS AB A DNA lesion created by oxidative stress is 7,8-dihydro-8-oxo-guanine (8-oxoG). Because 8-oxoG can mispair with adenine during DNA synthesis, it is of interest to understand the efficiency and fidelity of 8-oxoG bypass by DNA polymerases. We quantify bypass parameters for two DNA polymerases implicated in 8-oxoG bypass, Pols and . Yeast Pol and yeast Pol both bypass 8-oxoG and misincorporate adenine during bypass. However, yeast Pol is 10-fold more efficient than Pol , and following bypass Pol switches to less processive synthesis, similar to that observed during bypass of a cis-syn thymine-thymine dimer. Moreover, yeast Pol is at least 10-fold more accurate than yeast Pol during 8-oxoG bypass. These differences are maintained in the presence of the accessory proteins RFC, PCNA and RPA and are consistent with the established role of Pol in suppressing ogg1-dependent mutagenesis in yeast. Surprisingly different results are obtained with human and mouse Pol . Both mammalian enzymes bypass 8-oxoG efficiently, but they do so less processively, without a switch point and with much lower fidelity than yeast Pol . The fact that yeast and mammalian Pol have intrinsically different catalytic properties has potential biological implications. C1 [McCulloch, Scott D.; Kokoska, Robert J.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [McCulloch, Scott D.; Kokoska, Robert J.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Garg, Parie; Burgers, Peter M.] Washington Univ, Dept Biochem & Mol Biophys, Sch Med, St Louis, MO 63110 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU NIH [GM032431]; National Institute of Environmental Health Sciences FX NIH Grant GM032431 [to P. M. B.]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [to T. A. K.]. Funding for open access charge: Intramural Research Program, National Institutes of Health, National Institute of Environmental Health Sciences. NR 71 TC 46 Z9 49 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY PY 2009 VL 37 IS 9 BP 2830 EP 2840 DI 10.1093/nar/gkp103 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 449UB UT WOS:000266354600007 PM 19282446 ER PT J AU Marquez, VE Schroeder, GK Ludek, OR Siddiqui, MA Ezzitouni, A Wolfenden, R AF Marquez, Victor E. Schroeder, Gottfried K. Ludek, Olaf R. Siddiqui, Maqbool A. Ezzitouni, Abdallah Wolfenden, Richard TI CONTRASTING BEHAVIOR OF CONFORMATIONALLY LOCKED CARBOCYCLIC NUCLEOSIDES OF ADENOSINE AND CYTIDINE AS SUBSTRATES FOR DEAMINASES SO NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS LA English DT Article DE Adenosine deaminase; cytidine deaminase; carbocyclic nucleosides; bicyclo[3.1.0]hexane nucleosides ID TRANSITION-STATE ANALOG; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; PSEUDOROTATIONAL EQUILIBRIUM; PENTOFURANOSE MOIETY; POTENT INHIBITORS; BACILLUS-SUBTILIS; STABILIZATION; CATALYSIS; HYDRATION AB In addition to the already known differences between adenosine deaminase (ADA) and cytidine deaminase (CDA) in terms of their tertiary structure, the sphere of Zn(+2) coordination, and their reverse stereochemical Preference, we present evidence that the enzymes also differ significantly in term of the North/South conformational preferences for their substrates and the extent to which the lack of the O(4') oxygen affects the kinetics of the enzymatic deamination of carbocyclic substrates. The carbocyclic nucleoside substrates used in this study have either a flexible cyclopentane ring or a rigid bicyclo[3.1.0]hexane scaffold. C1 [Marquez, Victor E.; Ludek, Olaf R.; Siddiqui, Maqbool A.; Ezzitouni, Abdallah] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21703 USA. [Schroeder, Gottfried K.; Wolfenden, Richard] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21703 USA. EM marquez@dc37a.nci.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research; [GM-18325] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by grant GM-I 8325 (D.W. and G.K.S.). The authors thank Dr. Megan Peach of the LMC for helping with the analysis and display of the crystal structures. NR 42 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1525-7770 J9 NUCLEOS NUCLEOT NUCL JI Nucleosides Nucleotides Nucleic Acids PD MAY-JUL PY 2009 VL 28 IS 5-7 BP 614 EP 632 DI 10.1080/15257770903091904 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 489SS UT WOS:000269443400019 PM 20183605 ER PT J AU Blackburn, GL Hutter, MM Harvey, AM Apovian, CM Boulton, HRW Cummings, S Fallon, JA Greenberg, I Jiser, ME Jones, DB Jones, SB Kaplan, LM Kelly, JJ Kruger, RS Lautz, DB Lenders, CM LoNigro, R Luce, H McNamara, A Mulligan, AT Paasche-Orlow, MK Perna, FM Pratt, JSA Riley, SM Robinson, MK Romanelli, JR Saltzman, E Schumann, R Shikora, SA Snow, RL Sogg, S Sullivan, MA Tarnoff, M Thompson, CC Wee, CC Ridley, N Auerbach, J Hu, FB Kirle, L Buckley, RB Annas, CL AF Blackburn, George L. Hutter, Matthew M. Harvey, Alan M. Apovian, Caroline M. Boulton, Hannah R. W. Cummings, Susan Fallon, John A. Greenberg, Isaac Jiser, Michael E. Jones, Daniel B. Jones, Stephanie B. Kaplan, Lee M. Kelly, John J. Kruger, Rayford S., Jr. Lautz, David B. Lenders, Carine M. LoNigro, Robert Luce, Helen McNamara, Anne Mulligan, Ann T. Paasche-Orlow, Michael K. Perna, Frank M. Pratt, Janey S. A. Riley, Stancel M., Jr. Robinson, Malcolm K. Romanelli, John R. Saltzman, Edward Schumann, Roman Shikora, Scott A. Snow, Roger L. Sogg, Stephanie Sullivan, Mary A. Tarnoff, Michael Thompson, Christopher C. Wee, Christina C. Ridley, Nancy Auerbach, John Hu, Frank B. Kirle, Leslie Buckley, Rita B. Annas, Catherine L. TI Expert Panel on Weight Loss Surgery: Executive Report Update SO OBESITY LA English DT Article ID LAPAROSCOPIC SLEEVE GASTRECTOMY; GASTRIC BYPASS-SURGERY; SERVICES-TASK-FORCE; LONG-TERM MORTALITY; HIGH-RISK PATIENTS; QUALITY-OF-LIFE; BARIATRIC-SURGERY; MORBID-OBESITY; UNITED-STATES; BILIOPANCREATIC DIVERSION AB Rapid shifts in the demographics and techniques of weight loss surgery (WLS) have led to new issues, new data, new concerns, and new challenges. In 2004, this journal published comprehensive evidence-based guidelines on WLS. In this issue, we've updated those guidelines to assure patient safety in this fast-changing field. WLS involves a uniquely vulnerable population in need of specialized resources and ongoing multidisciplinary care. Timely best-practice updates are required to identify new risks, develop strategies to address them, and optimize treatment. Findings in these reports are based on a comprehensive review of the most current literature on WLS; they directly link patient safety to methods for setting evidence-based guidelines developed from peer-reviewed scientific publications. Among other outcomes, these reports show that WLS reduces chronic disease risk factors, improves health, and confers a survival benefit on those who undergo it. The literature also shows that laparoscopy has displaced open surgery as the predominant approach; that government agencies and insurers only reimburse procedures performed at accredited WLS centers; that best practice care requires close collaboration between members of a multidisciplinary team; and that new and existing facilities require wide-ranging changes to accommodate growing numbers of severely obese patients. More than 100 specialists from across the state of Massachusetts and across the many disciplines involved in WLS came together to develop these new standards. We expect them to have far-reaching effects of the development of health care policy and the practice of WLS. C1 [Blackburn, George L.; Jones, Daniel B.] Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. [Hutter, Matthew M.; Pratt, Janey S. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Harvey, Alan M.] Mercy Med Ctr Catholic Hlth E, Dept Anesthesiol, Springfield, MA USA. [Apovian, Caroline M.; Lenders, Carine M.] Boston Med Ctr, Dept Med, Boston, MA USA. [Boulton, Hannah R. W.] S Shore Hosp, Dept Nursing, Weymouth, MA USA. [Cummings, Susan] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Fallon, John A.] Blue Cross & Blue Shield Massachusetts, Boston, MA USA. [Greenberg, Isaac] Tufts Univ New England Med Ctr, Obes Consult Ctr, Boston, MA USA. [Jiser, Michael E.] Saints Med Ctr, Dept Surg, Lowell, MA USA. [Jones, Stephanie B.] Beth Israel Deaconess Med Ctr, Dept Anesthesiol, Boston, MA 02215 USA. [Kaplan, Lee M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kelly, John J.] Univ Massachusetts, Mem Med Ctr, Dept Surg, Worcester, MA 01605 USA. [Kruger, Rayford S., Jr.] Tobey Hosp, Dept Surg, Wareham, MA USA. [Lautz, David B.; Robinson, Malcolm K.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [LoNigro, Robert] Tufts Hlth Plan, Care Management, Boston, MA USA. [Luce, Helen] Consumer Representat, Boston, MA USA. [McNamara, Anne] Beth Israel Deaconess Med Ctr, Dept Nursing & Surg, Boston, MA 02215 USA. [Mulligan, Ann T.] Newton Wellesley Hosp, Dept Nursing, Newton, MA USA. [Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Perna, Frank M.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Riley, Stancel M., Jr.] Massachusetts Board Registrat Med, Patient Care Assessment Div, Boston, MA USA. [Robinson, Malcolm K.] Baystate Med Ctr, Dept Surg, Springfield, MA 01107 USA. [Saltzman, Edward] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. [Schumann, Roman] Tufts Univ New England Med Ctr, Dept Anesthesiol, Boston, MA USA. [Shikora, Scott A.; Tarnoff, Michael] Tufts Univ New England Med Ctr, Dept Surg, Boston, MA USA. [Snow, Roger L.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Snow, Roger L.] MassHealth, Boston, MA USA. [Sogg, Stephanie] Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [Sogg, Stephanie] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Sullivan, Mary A.] Lahey Clin & Massachusetts Coalit Prevent Med Err, Div Med Specialties, Burlington, MA USA. [Thompson, Christopher C.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Wee, Christina C.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Ridley, Nancy; Auerbach, John; Hu, Frank B.; Kirle, Leslie; Buckley, Rita B.; Annas, Catherine L.] Commonwealth Massachusetts, Betsy Lehman Ctr Patient Safety & Med Error Reduc, Boston, MA USA. RP Blackburn, GL (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. EM gblackbu@bidmc.harvard.edu OI Paasche-Orlow, Michael/0000-0002-9276-7190; Apovian, Caroline/0000-0002-8029-1922; Jones, Stephanie/0000-0001-8342-0374 NR 80 TC 54 Z9 54 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2009 VL 17 IS 5 BP 842 EP 862 DI 10.1038/oby.2008.578 PG 21 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 440OO UT WOS:000265709800002 PM 19396063 ER PT J AU Greenberg, I Sogg, S Perna, FM AF Greenberg, Isaac Sogg, Stephanie Perna, Frank M. TI Behavioral and Psychological Care in Weight Loss Surgery: Best Practice Update SO OBESITY LA English DT Article ID QUALITY-OF-LIFE; NIGHT EATING SYNDROME; BARIATRIC SURGERY; GASTRIC BYPASS; PSYCHOSOCIAL PREDICTORS; OBESITY SURGERY; MORBID-OBESITY; MENTAL-HEALTH; CANDIDATES; DISORDERS AB The objective of this study is to update evidence-based best practice guidelines for psychological evaluation and treatment of weight loss surgery (WLS) patients. We performed a systematic search of English-language literature on WLS and mental health, quality of life, and behavior modification published between April 2004 and May 2007 in MEDLINE and the Cochrane Library. Key words were used to narrow the search for a selective review of abstracts, retrieval of full articles, and grading of evidence according to systems used in established evidence-based models. Our literature search identified 17 articles of interest; 13 of the most relevant were reviewed in detail. From these, we developed evidence-based best practice recommendations on the psychological assessment and treatment of WLS patients. Regular updates of evidence-based recommendations for best practices in psychological care are required to address the impact of mental health on short- and long-term outcomes after WLS. Key factors in patient safety include comprehensive preoperative evaluation, use of appropriate and reliable evaluation instruments, and the development of short- and long-term treatment plans. C1 [Greenberg, Isaac] Tufts Sch Med, Dept Psychiat, Boston, MA USA. [Sogg, Stephanie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Weight Ctr, Boston, MA USA. [Perna, Frank M.] NCI, Hlth Promot Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Greenberg, I (reprint author), Tufts Sch Med, Dept Psychiat, Boston, MA USA. EM igreenberg@tufts-nemc.org FU NIDDK NIH HHS [P30-DK-46200] NR 40 TC 48 Z9 50 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2009 VL 17 IS 5 BP 880 EP 884 DI 10.1038/oby.2008.571 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 440OO UT WOS:000265709800005 PM 19396066 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Gail, MH AF Flegal, Katherine M. Graubard, Barry I. Williamson, David F. Gail, Mitchell H. TI Biased Corrections or Biased About Corrections? Response SO OBESITY LA English DT Letter ID OBESITY C1 [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Graubard, Barry I.; Gail, Mitchell H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Williamson, David F.] Emory Univ, Rollins Sch Publ Hlth, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. EM KFlegal@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 5 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2009 VL 17 IS 5 BP 940 EP 940 DI 10.1038/oby.2009.13 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 440OO UT WOS:000265709800022 ER PT J AU Treuth, MS Baggett, CD Pratt, CA Going, SB Elder, JP Charneco, EY Webber, LS AF Treuth, Margarita S. Baggett, Chris D. Pratt, Charlotte A. Going, Scott B. Elder, John P. Charneco, Eileen Y. Webber, Larry S. TI A Longitudinal Study of Sedentary Behavior and Overweight in Adolescent Girls SO OBESITY LA English DT Article ID MIDDLE-SCHOOL GIRLS; PHYSICAL-ACTIVITY; UNITED-STATES; BODY-COMPOSITION; OBESITY; CHILDREN; TRIAL; ASSOCIATIONS; WEIGHT; TIME AB The aim of this study is to examine sedentary and light activity in relation to overweight in adolescent girls. Adolescent girls were randomly recruited from 36 schools participating in the Trial of Activity for Adolescent Girls (TAAG). Assessments included age, ethnicity, socioeconomic status, and body composition estimated from weight, height, and triceps skinfold. Sedentary and light activity was measured for 6 days using accelerometry in 6th and in 8th grade among two randomly sampled cross-sections of girls. Sedentary activity increased from the 6th to 8th grade by 51.5 min/day. In the 8th grade, a significantly higher number of hours in sedentary activity for each of the 6-days of measurement were evident with higher tertiles of percent body fat (30-35%, > 35% fat) (P < 0.05), but not across all increasing tertiles of BMI (5th to 85th, 85th to 95th, and > 95th percentiles). The increase in sedentary activity was observed on weekdays, but not on weekends for percent body fat tertiles. In the cohort of girls measured in both 6th and 8th grades, the mean cross-sectional coefficient estimates were significant for percent body fat, but not BMI for sedentary and light activities. Adolescent girls from the 6th to 8th grade are shifting their time from light to more sedentary activity as measured by accelerometers. In addition, the increase in sedentary activity is not associated with an adverse effect on BMI or percent body fat. The eventual impact of this shift to a more sedentary lifestyle on body composition and other outcomes needs to be evaluated further. Obesity (2009) 17, 1003-1008. doi:10.1038/oby.2008.598 C1 [Treuth, Margarita S.] Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD USA. [Baggett, Chris D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Pratt, Charlotte A.; Charneco, Eileen Y.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Going, Scott B.] Univ Arizona, Dept Physiol, Tucson, AZ USA. [Elder, John P.] San Diego State Univ, Grad Sch Publ Hlth, Div Hlth Promot & Behav Sci, San Diego, CA 92182 USA. [Webber, Larry S.] Tulane Univ, Dept Biostat, New Orleans, LA 70118 USA. RP Treuth, MS (reprint author), Univ Maryland Eastern Shore, Dept Phys Therapy, Princess Anne, MD USA. EM mtreuth@umes.edu FU National Heart, Lung, and Blood Institute [U01HL66858, U01HL66857, U01HL66845, U01HL66856, U01HL66855, U01HL66853, U01HL66852] FX We sincerely thank all the girls who participated in the TAAG trial and the faculty and staff at each of the participating 36 schools. We also thank all the support staff at each of the field centers, coordinating center, and project office for their tremendous efforts in implementing this trial. This research was funded by grants from the National Heart, Lung, and Blood Institute (U01HL66858, U01HL66857, U01HL66845, U01HL66856, U01HL66855, U01HL66853, U01HL66852). NR 26 TC 33 Z9 33 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2009 VL 17 IS 5 BP 1003 EP 1008 DI 10.1038/oby.2008.598 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 440OO UT WOS:000265709800030 PM 19165170 ER PT J AU Beasley, LE Koster, A Newman, AB Javaid, MK Ferrucci, L Kritchevsky, SB Kuller, LH Pahor, M Schaap, LA Visser, M Rubin, SM Goodpaster, BH Harris, TB AF Beasley, Lydia E. Koster, Annemarie Newman, Anne B. Javaid, M. Kassim Ferrucci, Luigi Kritchevsky, Stephen B. Kuller, Lewis H. Pahor, Marco Schaap, Laura A. Visser, Marjolein Rubin, Susan M. Goodpaster, Bret H. Harris, Tamara B. CA Health ABC Study TI Inflammation and Race and Gender Differences in Computerized Tomography-measured Adipose Depots SO OBESITY LA English DT Article ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; BODY-FAT DISTRIBUTION; VISCERAL FAT; INSULIN-RESISTANCE; METABOLIC SYNDROME; ABDOMINAL FAT; DIABETES-MELLITUS; TISSUE; OBESITY AB A growing body of evidence has consistently shown a correlation between obesity and chronic subclinical inflammation. It is unclear whether the size of specific adipose depots is more closely associated with concentrations of inflammatory markers than overall adiposity. This study investigated the relationship between inflammatory markers and computerized tomography-derived abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat in older white and black adults. Data were from 2,651 black and white men and women aged 70-79 years participating in the Health, Aging, and Body Composition (Health ABC) study. Inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were obtained from serum samples. Abdominal visceral and subcutaneous fat and thigh intermuscular and subcutaneous fat were quantified on computerized tomography images. Linear regression analysis was used to evaluate the cross-sectional relationship between specific adipose depots and inflammatory markers in four race/gender groups. As expected, blacks have less visceral fat than whites and women less visceral fat than men. However, abdominal visceral adiposity was most consistently associated with significantly higher IL-6 and CRP concentrations in all race/gender groups (P < 0.05), even after controlling for general adiposity. Thigh intermuscular fat had an inconsistent but significant association with inflammation, and there was a trend toward lower inflammatory marker concentration with increasing thigh subcutaneous fat in white and black women. Despite the previously established differences in abdominal fat distribution across gender and race, visceral fat remained a significant predictor of inflammatory marker concentration across all four subgroups examined. Obesity (2009) 17, 1062-1069. doi:10.1038/oby.2008.627 C1 [Beasley, Lydia E.; Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Beasley, Lydia E.] Washington Univ, Dept Biomed Engn, St Louis, MO USA. [Koster, Annemarie] Univ Maastricht, Fac Hlth Med & Life Sci, Maastricht, Netherlands. [Newman, Anne B.; Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Javaid, M. Kassim] Univ Southampton, MRC Epidemiol Resource Ctr, Southampton, Hants, England. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Sect Gerontol & Geriatr Med, Sticht Ctr Aging, Winston Salem, NC USA. [Pahor, Marco] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL USA. [Schaap, Laura A.] Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Amsterdam, Netherlands. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Koster, A (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM kostera@mail.nih.gov RI Koster, Annemarie/E-7438-2010; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health, National Institute on Aging FX This study was supported by National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The authors' responsibilities were as follows-L. E. B.: data analysis and interpretation, drafting of the manuscript; A. K.: study design, data interpretation, drafting of the manuscript, and critical revision of the manuscript; A. B. N., M. K. J., L. F., S. B. K., L. H. K., M. P., L. A. S., M. V., S. M. R., B. H. G.: critical revision of the manuscript; T. B. H.: study design, interpretation of the data, and revision of the manuscript. There is no personal or financial conflict of interest among any of the authors. NR 29 TC 81 Z9 83 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD MAY PY 2009 VL 17 IS 5 BP 1062 EP 1069 DI 10.1038/oby.2008.627 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 440OO UT WOS:000265709800039 PM 19165157 ER PT J AU Tita, ATN Landon, MB Spong, CY Lai, YL Leveno, KJ Varner, MW Moawad, AH Caritis, SN Meis, PJ Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, AM O'Sullivan, MJ Sihai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM AF Tita, Alan T. N. Landon, Mark B. Spong, Catherine Y. Lai, Yinglei Leveno, Kenneth J. Varner, Michael W. Moawad, Atef H. Caritis, Steve N. Meis, Paul J. Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem Carpenter, Marshall Peaceman, Alan M. O'Sullivan, Mary J. Sihai, Baha M. Langer, Oded Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Eunice Kennedy Shriver NICHD Mater TI Timing of Elective Repeat Cesarean Delivery at Term and Neonatal Outcomes SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB The risk of neonatal adverse respiratory outcomes is higher among infants delivered before 39 weeks' gestation than after 39 weeks', and among infants delivered by prelabor cesarean compared to those delivered vaginally. Thus, elective cesarean section before 39 weeks is discouraged in the absence of fetal lung maturity. This prospective study compared neonatal outcomes among infants delivered by elective cesarean delivery at 37, 38, and 39 weeks' gestation. The study cohort was pregnant women with viable singleton pregnancies undergoing repeat cesarean delivery at 19 academic medical centers. The women were delivered before onset of labor and had no medical or obstetrical indications for delivery before 39 weeks. The primary study outcome was a composite of any adverse neonatal outcome or death. Adverse outcomes included respiratory complications, admission to the neonatal intensive care unit (ICU), newborn sepsis, treated hypoglycemia, and hospitalization for 5 days or longer. Logistic regression models were used to calculate adjusted odds ratios for the association between neonatal outcomes and gestational age at birth relative to 39 completed weeks. Among the study cohort, 13,258 women underwent elective repeat cesarean section at term. Of these, 49.1 % had the procedure at 39 weeks', and 35.8% had the procedure before 39 completed weeks' gestation (6.3% at 37 weeks and 29.5% at 38 weeks). With increasing gestational age at birth, the risk of the primary outcome decreased. Unadjusted analysis showed that the incidence of the primary outcome was 15.3% at 37 weeks, 11.0% at 38 weeks, and 8.0% at 39 weeks (P for trend <0.001). The differences remained after adjusting for variables (P for trend <0.001). The adjusted risk of individual adverse outcomes including adverse respiratory complications, admission to the neonatal ICU, newborn sepsis, hypoglycemia, admission to the neonatal ICU, and hospitalization for 5 days or more were increased by a factor of 1.8 to 4.2 for births at 37 weeks and 1.3 to 2.1 for births at 38 weeks, relative to births at 39 weeks' gestation. There was only I neonatal death, of an infant born at 39 weeks. These findings suggest that postponing elective delivery to 39 weeks might prevent a significant number of adverse neonatal outcomes or deaths, and support recommendations to delay elective delivery until 39 weeks' gestation. C1 [Tita, Alan T. N.] Univ Alabama, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Utah, Salt Lake City, UT USA. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL USA. Univ Tennessee, Memphis, TN USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas Hlth Sci Ctr, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Tita, ATN (reprint author), Univ Alabama, Birmingham, AL USA. RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2009 VL 64 IS 5 BP 293 EP 295 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 438OY UT WOS:000265566200006 ER PT J AU Castle, PE Schiffman, M Wheeler, CM Solomon, D AF Castle, Philip E. Schiffman, Mark Wheeler, Cosette M. Solomon, Diane TI Evidence for Frequent Regression of Cervical Intraepithelial Neoplasia-Grade 2 SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB There is increasing evidence that a significant proportion of CIN 2 lesions found in cervical cancer screening programs are not precancerous and may resolve without treatment. The present study evaluated the percentage of CIN 2 regression if untreated using three different management strategies for referring women to colposcopy using data from the Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS). Over the 2-year duration of the ALTS, the investigators compared the cumulative occurrence of CIN 2 (n = 397) and CIN 3 or more severe (n = 542) in three treatment arms: 1) conservative management (CM arm) (referral to colposcopy only if the lesion at baseline was identified by cytology as high-grade squamous intraepithelial lesion [HSIL]); 2) human papillomavirus (HPV) triage (HPV arm) (referral to colposcopy if the HPV test result at baseline was positive, missing, or identified by cytology as HSIL); or 3) immediate colposcopy (IC arm) (referral of all patients to colposcopy at baseline). A nonparametric test for trend across study arms was used to test for differences in the number of CIN 2 cases relative to number of CIN 3 or more severe cases referred to colposcopy. At baseline, 10.2% of the women in the CM arm, 55.5% of women in the HPV arm, and 71.7% of women in the IC arm were sent to colposcopy. Over the 2-year duration of ALTS, the proportion of women diagnosed with CIN 3 or more severe did not differ significantly among the three study arms: CM, 10.9%; HPV, 10.3%; and IC, 10-9% (P(trend) = 0.8). However, the percentage of women diagnosed with CIN 2 was significantly greater for the referral strategies that sent larger proportions of women to colposcopy: CM, 5.8%; HPV, 7.8%; and IC, 9.9% (P(trend) < 0.001). Among high-risk-HPV genotypes identified at baseline (except HPV 16), the trend of increased CIN 2 diagnoses by study arm with increasing proportion of women sent to colposcopy also was observed (P(trend) = 0.01); among women with HPV 16, the trend was nonsignificant (P(trend) = 0.1). These data suggest that over 40% of CIN 2 diagnosed over 2 years may represent regressive lesions destined to resolve without treatment. A similar pattern occurs in high-risk-HPV genotypes except HPV 16-positive CIN 2, which appears less likely to regress. C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Services, Bethesda, MD 20892 USA. NCI, Canc Prevent Div, NIH, Dept Hlth & Human Services, Bethesda, MD 20892 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Services, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2009 VL 64 IS 5 BP 306 EP 308 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 438OY UT WOS:000265566200013 ER PT J AU Subak, LL Wing, R West, DS Franklin, F Vittinghoff, E Creasman, JM Richter, HE Myers, D Burgio, KL Gorin, AA Macer, J Kusek, JW Grady, D Investigators, P AF Subak, Leslee L. Wing, Rena West, Delia Smith Franklin, Frank Vittinghoff, Eric Creasman, Jennifer M. Richter, Hotly E. Myers, Deborah Burgio, Kathryn L. Gorin, Amy A. Macer, Judith Kusek, John W. Grady, Deborah Investigators, P. R. I. D. E. TI Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material AB Obesity is a strong risk factor for urinary incontinence. Although marked weight loss after bariatric surgery in morbidly obese women was associated in previous studies with a reduction in urinary incontinence, the overall evidence for a benefit of weight loss in obese women is inconclusive. In this randomized clinical trial, the Program to Reduce Incontinence by Diet and Exercise, the potential benefits of a behavioral weight-reduction intervention were compared with a structured educational program in 338 overweight and obese women with at least 10 urinary incontinence episodes per week. The study subjects were randomized to receive either an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (intervention group, n = 226) or a structured education program consisting of general information about healthy eating, physical activity, and weight loss (control group, n = 112). The mean (+/- SD) age of the study subjects was 53 +/- 11 years. Body-mass index (BMI) was calculated as the weight in kilograms divided by the square of the height in meters. The primary study outcome was the change in the total number of self-reported incontinence episodes of any type (including stress and urge incontinence) recorded in a 7-day voiding diary at 6 months after randomization. At baseline, the mean BMI and the total number of incontinence episodes per week were the same in the intervention and control groups (BMI, 36 6 vs. 36 5, respectively; incontinence episodes, 24 18 vs. 24 16, respectively). At 6 months, the mean weight loss among women in the intervention group was 8.0% (7.8 kg), whereas the mean weight loss among women in the control group was 1.6% (1.5 kg) (P < .001). There was a greater decrease in total number of incontinence episodes per week in the intervention group at 6 months compared with the control group (intervention: 47.4% vs. control: 28.1%, P = 0.01). The frequency of stress incontinence episodes was reduced more in the intervention group (57.6%) than the control group (32.7%, P = 0.02). The frequency of episodes of urge incontinence was also decreased more in the intervention group (42.4% vs. 26.0%), but the difference was not statistically significant (P = 0.14). In comparison with the control group, a higher proportion of women in the intervention group reported a clinically meaningful reduction of at least 70% in the total weekly number of episodes of any type of incontinence (P < 0.001), stress-incontinence (P = 0.009), and urge-incontinence (P = 0.04). The investigators conclude from these findings that weight loss should be considered as a first-line treatment in overweight and obese women with incontinence. C1 [Subak, Leslee L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. Univ Alabama, Birmingham, AL USA. Ctr Geriatr Res Educ & Clin, Dept Vet Affairs, Birmingham, AL USA. Univ Connecticut, Storrs, CT USA. NIDDK, Bethesda, MD USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Subak, LL (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD MAY PY 2009 VL 64 IS 5 BP 317 EP 318 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 438OY UT WOS:000265566200019 ER PT J AU Chattopadhyay, I Phukan, R Singh, A Vasudevan, M Purkayastha, J Hewitt, S Kataki, A Mahanta, J Kapur, S Saxena, S AF Chattopadhyay, Indranil Phukan, Rupkumar Singh, Avninder Vasudevan, Madavan Purkayastha, Joydeep Hewitt, Stepen Kataki, Amal Mahanta, Jagadish Kapur, Sujala Saxena, Sunita TI Molecular profiling to identify molecular mechanism in esophageal cancer with familial clustering SO ONCOLOGY REPORTS LA English DT Article DE expression profile; familial esophageal cancer; microarray ID SQUAMOUS-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; GASTRIC-CANCER; TUMOR-CELLS; EXPRESSION; ANGIOGENESIS; ARGINASE; DEATH AB To identify the genes and molecular functional pathways involved in esophageal cancer, we analyzed the gene expression profile of esophageal tumor tissue from patients having family history of esophageal cancer by cDNA microarray. Three hundred and fifty differentially expressed genes (26 up-regulated and 324 down-regulated) were identified. Genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-beta signaling (SMAD1) and calcium signaling pathways (VDAC1) were down-regulated and genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A) were up-regulated. Validation of differential expression of subset of genes by QRT-PCR and tissue microarray in familial and non-familial cases showed no significant difference in expression of these genes in two groups suggesting familial clustering occurs as result of sharing of common environmental factors. Gene expression profiling of clinical specimens from well characterized populations that have familial clustering of cancer identified molecular mechanism associated with progression of esophageal cancer. C1 [Chattopadhyay, Indranil; Singh, Avninder; Kapur, Sujala; Saxena, Sunita] Inst Pathol, New Delhi 110029, India. [Purkayastha, Joydeep; Kataki, Amal] Dr B Borooah Canc Inst, Gauhati 781016, Assam, India. [Phukan, Rupkumar; Mahanta, Jagadish] Reg Med Res Ctr, Dibrugarh 786001, Assam, India. [Vasudevan, Madavan] Genotyp Technol P Ltd, Bangalore 560001, Karnataka, India. [Hewitt, Stepen] NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Saxena, S (reprint author), Inst Pathol, Safdarjung Hosp Campus, New Delhi 110029, India. EM sunita_saxena@yahoo.com OI Hewitt, Stephen/0000-0001-8283-1788 NR 28 TC 19 Z9 20 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD MAY PY 2009 VL 21 IS 5 BP 1135 EP 1146 DI 10.3892/or_00000333 PG 12 WC Oncology SC Oncology GA 434KV UT WOS:000265274500001 PM 19360286 ER PT J AU Yeh, S Karne, NK Kerkar, SP Heller, CK Palmer, DC Johnson, LA Li, ZQ Bishop, RJ Wong, WT Sherry, RM Yang, JC Dudley, ME Restifo, NP Rosenberg, SA Nussenblatt, RB AF Yeh, Steven Karne, Neel K. Kerkar, Sid P. Heller, Charles K. Palmer, Douglas C. Johnson, Laura A. Li, Zhuqing Bishop, Rachel J. Wong, Wai T. Sherry, Richard M. Yang, James C. Dudley, Mark E. Restifo, Nicholas P. Rosenberg, Steven A. Nussenblatt, Robert B. TI Ocular and Systemic Autoimmunity after Successful Tumor-Infiltrating Lymphocyte Immunotherapy for Recurrent, Metastatic Melanoma SO OPHTHALMOLOGY LA English DT Article ID KOYANAGI-HARADA-DISEASE; ADOPTIVE CELL TRANSFER; MALIGNANT-MELANOMA; MACULAR EDEMA; CANCER-IMMUNOTHERAPY; ANTIGEN-4 BLOCKADE; TRANSFER THERAPY; T-CELLS; UVEITIS; VITILIGO AB Objective: To describe the ophthalmic and systemic autoimmune findings after successful adoptive cell transfer of ex vivo expanded, autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) for metastatic melanoma. Design: Retrospective, interventional case report. Participant: A 35-year-old man who underwent immunotherapy for metastatic melanoma with adoptive cell transfer of tumor-reactive TIL. Methods: A 35-year-old man with metastatic melanoma was treated with TIL plus interleukin-2 (IL-2) therapy after a lymphodepleting regimen of cyclophosphamide and fludarabine for metastatic melanoma, which led to a complete and durable remission. Bilateral panuveitis, hearing loss, vitiligo, poliosis, and alopecia developed in the patient, requiring local ophthalmic immunosuppressive therapy. The clinical course, diagnostic testing, and therapeutic interventions over a 2-year period are reviewed. Main Outcome Measures: Visual acuity, anterior chamber and vitreous inflammation, optical coherence tomography findings, serial electro-oculograms (EOGs), microperimetry (MP-1) testing, flow cytometric analysis of cells derived from the aqueous humor, and aqueous humor cytokine profiles were evaluated. Results: After melanoma immunotherapy, complete tumor regression was achieved at 5 months after treatment with a durable, ongoing, complete remission at 24 months. Early in the treatment course, a high fever, a diffuse rash, hearing loss, and bilateral anterior uveitis developed acutely in the patient. Late autoimmune sequelae included the development of alopecia, vitiligo, poliosis, and bilateral panuveitis with diffuse retinal pigment epithelium (RPE) hypopigmentation, reminiscent of Vogt-Koyanagi-Harada (VKH) syndrome. Bilateral cystoid macular edema also developed that was responsive to acetazolamide. Serial EOGs showed alterations in RPE standing potentials in dark conditions, and MP-1 testing revealed diminished foveal and perifoveal sensitivity. An aqueous humor aspirate revealed a high concentration of melanoma tumor antigen-reactive T cells compared with that of peripheral blood samples, as well as a proinflammatory aqueous cytokine profile. At the time of cataract surgery 22 months after immunotherapy, a repeat aqueous humor sample showed the disappearance of the previously seen melanoma differentiation antigen-reactive lymphocytes, but the proinflammatory cytokine profile persisted. Conclusions: Ocular and systemic autoimmune sequelae resembling VKH may develop after successful melanoma immunotherapy. This report provides insight into the pathogenesis of VKH disease. The patient's clinical course illustrates the fine balance between tumor-specific immunity and loss of self-tolerance. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009;116:981-989 (C) 2009 by the American Academy of Ophthalmology. C1 [Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20814 USA. [Karne, Neel K.; Kerkar, Sid P.; Heller, Charles K.; Palmer, Douglas C.; Johnson, Laura A.; Sherry, Richard M.; Yang, James C.; Dudley, Mark E.; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20814 USA. EM DrBob@nei.nih.gov RI Restifo, Nicholas/A-5713-2008; Johnson, Laura/H-4861-2013; Palmer, Douglas/B-9454-2008; Wong, Wai/B-6118-2017; OI Palmer, Douglas/0000-0001-5018-5734; Wong, Wai/0000-0003-0681-4016; Restifo, Nicholas P./0000-0003-4229-4580 FU National Cancer Institute; National Eye Institute, National Institutes of Health, Bethesda, Maryland; Heed Ophthalmic Foundation; Cleveland Clinic Foundation, Cleveland, Ohio FX Supported by the Intramural Research Programs of the National Cancer Institute and National Eye Institute, National Institutes of Health, Bethesda, Maryland. Dr Yeh is supported by the Heed Ophthalmic Foundation, Cleveland Clinic Foundation, Cleveland, Ohio. NR 29 TC 41 Z9 42 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2009 VL 116 IS 5 BP 981 EP U179 DI 10.1016/j.ophtha.2008.12.004 PG 10 WC Ophthalmology SC Ophthalmology GA 508DI UT WOS:000270907500024 PM 19410956 ER PT J AU Jonsson, H Eliasson, GJ Jonsson, A Eiriksdottir, G Sigurosson, S Aspelund, T Harris, TB Guonason, V AF Jonsson, H. Eliasson, G. J. Jonsson, A. Eiriksdottir, G. Sigurosson, S. Aspelund, T. Harris, T. B. Guonason, V. TI High hand joint mobility is associated with radiological CMC1 osteoarthritis: the AGES-Reykjavik study SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Hand osteoarthritis; Radiology; Hypermobility; Epidemiology ID ARTICULAR HYPERMOBILITY; POPULATION; PREVALENCE; PAIN AB Objective: Previous studies have indicated that joint hypermobility may affect the development of clinical and radiological hand osteoarthritis (OA), but this question has not been addressed in epidemiological studies. Our objective was to investigate this relationship in a population-based study. Patients and methods: The study group consisted of 384 unselected older participants in the Age, Gene/Environment Susceptibility-Reykjavik Study (161 males, median age 76, range 69-90, and 223 females median age 75, range 69-92). The criterion used for joint mobility was the single maximal degree of hyperextension of digits 2 and 5 on both hands (HYP degrees). Results: HYP degrees was more prevalent in females and on the left hand in both men and women. Both genders had a positive association between the degree of mobility measured by HYP degrees and radiological scores for the first carpometacarpal joint (CMC1) OA. Thus, those with HYP degrees >= 70 had an odds ratio of 3.05 (1.69-5.5, P<0.001) of having a Kellgren-Lawrence score of >= 3 in a CMC1 joint. There was also a trend towards a negative association between HYP degrees and proximal interphalangeal joint scores. Conclusion: Hand joint mobility, defined as hyperextension in the metacarpophalangeal joints (HYP degrees) is more prevalent in females and on the left side. It was associated with more severe radiographic OA in the CMC1 joints in this population. The reasons for this relationship are not known, but likely explanations involve ligament laxity and CMC1 joint stability. These findings may relate to the left-sided predominance of radiographic OA in the CMC1 joints observed in many prevalence studies. (C) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Jonsson, H.; Jonsson, A.] Landspitalinn Univ Hosp, Reykjavik, Iceland. [Eliasson, G. J.] Roentgen Domus Med & Landspitalinn Univ Hosp, Reykjavik, Iceland. [Eiriksdottir, G.; Sigurosson, S.; Aspelund, T.; Guonason, V.] Iceland Heart Assoc, Reykjavik, Iceland. [Aspelund, T.; Guonason, V.] Univ Iceland, Reykjavik, Iceland. [Harris, T. B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. RP Jonsson, H (reprint author), Univ Hosp, Roentgen Domus Med & Landspitalinn, IS-101 Reykjavik, Iceland. EM helgijon@rsp.is RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 FU NIH [N01-AG12100]; NIA; Althingi; Icelandic Osteoarthritis Fund FX This study has been funded by NIH contract N01-AG12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063, the Icelandic Data Protection Authority and the Institutional Review Board serving NIA. The study was also supported by the Icelandic Osteoarthritis Fund. We would also like to thank Lauren Abbate for her contribution to the clinical examination for hypermobility. NR 21 TC 14 Z9 14 U1 0 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAY PY 2009 VL 17 IS 5 BP 592 EP 595 DI 10.1016/j.joca.2008.10.002 PG 4 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 446RU UT WOS:000266139600007 PM 19010064 ER PT J AU Chen, AM Klebanoff, MA Basso, O AF Chen, Aimin Klebanoff, Mark A. Basso, Olga TI Pre-pregnancy body mass index change between pregnancies and preterm birth in the following pregnancy SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE maternal body mass index; preterm delivery; consecutive pregnancies ID POSTPARTUM WEIGHT RETENTION; GESTATIONAL-AGE; PERINATAL OUTCOMES; BRAZILIAN WOMEN; UNITED-STATES; RISK; DELIVERY; POPULATION; COHORT; OBESITY AB Maternal pre-pregnancy body mass index (BMI) may affect the risk of preterm birth. However, it is unclear how changes in BMI between pregnancies modify the risk of preterm birth in the following pregnancy. We studied this effect in the Collaborative Perinatal Project, when obesity was uncommon and the prevalence of induction of labour was low. This analysis included 1892 primiparae whose first enrolled ( index) pregnancy was a singleton livebirth and the second enrolled ( outcome) pregnancy was a consecutive singleton pregnancy ( both pregnancies within 20-51 weeks of gestation). We used the Cox regression model to calculate the hazard ratio (HR) of preterm birth at the outcome pregnancy as a function of reduced BMI (<25(th) percentile of change) and increased BMI (>75(th) percentile), compared with stable BMI (25(th)-75(th) percentile), adjusted for pre-pregnancy BMI at the index pregnancy and other covariates. Body mass index reduction was associated with a non-significant increased risk of preterm birth, adjusted HR 1.17 [95% confidence interval 0.90, 1.53]; BMI increase had effects close to null (adjusted HR 1.08 [0.83, 1.41]). In the model with linear BMI change, each 1 kg/m(2) increase was associated with an HR of 0.96 [0.89, 1.03]. The estimates associated with a BMI reduction were higher in women whose index pregnancy ended preterm (HR 1.49 [0.90, 2.44]) and in those with BMI < 25 kg/m(2) at the index pregnancy (HR 1.30 [0.98, 1.71]). This study involved mainly low-to-normal weight women with spontaneous deliveries, and might suffer from type II error owing to small sample size. The effect of BMI change in overweight and obese women needs to be studied using contemporary data. C1 [Chen, Aimin] Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE 68178 USA. [Klebanoff, Mark A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Basso, Olga] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Chen, AM (reprint author), Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, 2500 Calif Plaza, Omaha, NE 68178 USA. EM aiminchen@creighton.edu RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU Creighton University School of Medicine Health Future Foundation; Intramural Research Program of the NIH; National Institute of Environmental Health Sciences [Z01 ES044003]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The study was supported by Creighton University School of Medicine Health Future Foundation. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences ( Z01 ES044003), and Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 40 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD MAY PY 2009 VL 23 IS 3 BP 207 EP 215 DI 10.1111/j.1365-3016.2009.01029.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 425KL UT WOS:000264635300003 PM 19775382 ER PT J AU Miller, SDM Mansky, PJ AF Miller, Scott D. M. Mansky, Patrick J. TI Nutritional Supplementation for Pediatric Cancer Cachexia: What Can We Feed Back? SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID EICOSAPENTAENOIC ACID; FISH-OIL; DOUBLE-BLIND; WEIGHT-LOSS; ANOREXIA/CACHEXIA C1 [Mansky, Patrick J.] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS,CRC, Bethesda, MD 20892 USA. RP Mansky, PJ (reprint author), NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, DHHS,CRC, 10 Ctr Dr,Rm 4-1741 MSC 1302, Bethesda, MD 20892 USA. EM manskyp@mail.nih.gov FU Intramural NIH HHS NR 13 TC 0 Z9 0 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2009 VL 52 IS 5 BP 557 EP 558 DI 10.1002/pbc.21933 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 418SK UT WOS:000264168800002 PM 19195032 ER PT J AU Nicholson, CE Dean, JM AF Nicholson, Carol E. Dean, J. Michael TI Looking for truth: In ourselves and in those we train SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Editorial Material DE pediatric critical care; training; research; time; departments; support; quality of research training C1 [Nicholson, Carol E.] Eunice Kennedy Shriver NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Dean, J. Michael] Univ Utah, Dept Pediat, Salt Lake City, UT USA. RP Nicholson, CE (reprint author), Eunice Kennedy Shriver NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD MAY PY 2009 VL 10 IS 3 BP 417 EP 418 DI 10.1097/PCC.0b013e31819adebb PG 2 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 444YG UT WOS:000266016200031 PM 19433953 ER PT J AU McDermott, DF Gammon, B Snijders, PJ Mbata, I Phifer, B Hartley, AH Lee, CCR Murphy, PM Hwang, ST AF McDermott, David F. Gammon, Bryan Snijders, Peter J. Mbata, Ihunanya Phifer, Beth Hartley, A. Howland Lee, Chyi-Chia Richard Murphy, Philip M. Hwang, Sam T. TI Autosomal Dominant Epidermodysplasia Verruciformis Lacking a Known EVER1 or EVER2 Mutation SO PEDIATRIC DERMATOLOGY LA English DT Article ID INTERFERON; PATIENT; GENE; PAPILLOMAVIRUSES; DISEASE; WARTS; MODEL AB Epidermodysplasia verruciformis is a rare genodermatosis characterized by abnormal susceptibility to infection with specific human papillomavirus serotypes. Epidermodysplasia verruciformis is a genetically heterogeneous disease, and autosomal recessive and X-linked inheritance patterns have been reported. Nonsense mutations in the genes EVER1 and EVER2 have been identified in over 75% of cases. We present epidermodysplasia verruciformis in a father and a son with typical histologic and clinical findings that occur in the absence of mutations in EVER1 or EVER2. Epidermodysplasia verruciformis in this father/son pair in a nonconsanguinous pedigree is consistent with autosomal dominant inheritance. This is the first report of autosomal dominant transmission of epidermodysplasia verruciformis, providing further evidence of the genetic heterogeneity of epidermodysplasia verruciformis. C1 [McDermott, David F.; Mbata, Ihunanya; Murphy, Philip M.] NIAID, Mol Signalling Sect, NIH, Bethesda, MD 20892 USA. [Gammon, Bryan; Hwang, Sam T.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Snijders, Peter J.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Mol Pathol Unit, Amsterdam, Netherlands. [Phifer, Beth; Hartley, A. Howland] So Maryland Skin Specialists, Prince Frederick, MD USA. [Hartley, A. Howland] George Washington Univ, Sch Med, Dept Dermatol & Pediat, Washington, DC USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 12C442, Bethesda, MD 20892 USA. EM hwangst@mail.nih.gov RI Lee, Chyi-Chia/I-1938-2013; OI Lee, Chyi-Chia/0000-0002-5306-7781; McDermott, David/0000-0001-6978-0867 FU NIH; NIH from Pfizer, Inc; NIH, National Cancer Institute, Center for Cancer Research; National Institute of Allergy, Immunology and Infectious Diseases FX BG was funded by a public-private partnership supported jointly by the NIH and a grant to the foundation for the NIH from Pfizer, Inc. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and the National Institute of Allergy, Immunology and Infectious Diseases. NR 19 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0736-8046 J9 PEDIATR DERMATOL JI Pediatr. Dermatol. PD MAY-JUN PY 2009 VL 26 IS 3 BP 306 EP 310 DI 10.1111/j.1525-1470.2008.00853.x PG 5 WC Dermatology; Pediatrics SC Dermatology; Pediatrics GA 456UC UT WOS:000266875900011 PM 19706093 ER PT J AU Smith, PB Walsh, TJ Hope, W Arrieta, A Takada, A Kovanda, LL Kearns, GL Kaufman, D Sawamoto, T Buell, DN Benjamin, DK AF Smith, P. Brian Walsh, Thomas J. Hope, William Arrieta, Antonio Takada, Akitsugu Kovanda, Laura L. Kearns, Gregory L. Kaufman, David Sawamoto, Taiji Buell, Donald N. Benjamin, Daniel K., Jr. TI Pharmacokinetics of an Elevated Dosage of Micafungin in Premature Neonates SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE antifungal; Candida; dosing; micafungin; premature infants ID BIRTH-WEIGHT INFANTS; AMPHOTERICIN-B; FUNGAL-INFECTIONS; ECHINOCANDIN; FLUCONAZOLE; CANDIDIASIS; SAFETY; FK463 AB Background: Determining the safety and pharmacokinetics of antifungal agents in neonates is important. A previous single-dose pharmacokinetic study of micafungin in neonates demonstrated that doses of 0.75 to 3 mg/kg produced lower plasma micafungin concentrations than in older patients because of increased apparent plasma clearance of micafungin in neonates. The primary objective of this study was to assess the safety and pharmacokinetics of an increased (15 mg/kg/d) dose of micafungin. Methods: A repeated dose, open-label pharmacokinetic, and safety trial of intravenous micafungin in 12 preterm neonates >48 hours of life with suspected systemic infections. Neonates received 15 mg/kg/d of micafungin for 5 days. Blood samples were drawn relative to either the fourth or fifth dose. Systemic exposure was assessed by examination of the plasma area under the curve. Results: The median birth weight and gestational age of the neonates were 775 g and 27 weeks, respectively. No adverse events related to micafungin were detected. The mean area under the curve and clearance for the cohort was 437.5 mu g'h/mL and 0.575 mL/min/kg, respectively. The calculated clearance and volume of distribution for neonates was greater than that observed in older children and adults. Conclusions: These data suggest that 15 mg/kg dosing in premature neonates corresponds to an exposure of approximately 5 mg/kg in adults. No adverse events related to micafungin were observed. C1 [Smith, P. Brian; Benjamin, Daniel K., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC 27715 USA. [Smith, P. Brian; Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27715 USA. [Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. [Hope, William] Univ Manchester, Manchester, Lancs, England. [Arrieta, Antonio] Childrens Hosp Orange Cty, Orange, CA USA. [Takada, Akitsugu] Astellas Pharma Inc, Tokyo, Japan. [Kovanda, Laura L.; Sawamoto, Taiji; Buell, Donald N.] Astellas Pharma US Inc, Deerfield, IL USA. [Kearns, Gregory L.] Univ Missouri, Childrens Mercy Hosp, Dept Pediat, Kansas City, MO 64108 USA. [Kearns, Gregory L.] Univ Missouri, Childrens Mercy Hosp, Div Pediat Pharmacol & Med Toxicol, Kansas City, MO 64108 USA. [Kaufman, David] Univ Virginia, Dept Pediat, Charlottesville, VA USA. RP Smith, PB (reprint author), Duke Univ, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM brian.smith@duke.edu RI Smith, Phillip/I-5565-2014; OI Hope, William/0000-0001-6187-878X FU Astellas Phanna US, Inc, Deerfield, IL [5U10HD045962-0]; Network of Pediatric Pharmacology Research Units; National Institutes of Health/National Institute for Child Health and Human Development (NIH(NICHD), Bethesda, MD [NIH-IK23HD060040-01] FX Supported by Astellas Phanna US, Inc, Deerfield, IL, and in part by grant 5U10HD045962-04, Network of Pediatric Pharmacology Research Units, National Institutes of Health/National Institute for Child Health and Human Development (NIH(NICHD), Bethesda, MD. Support also provided by NIH-IK23HD060040-01. NR 21 TC 69 Z9 71 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2009 VL 28 IS 5 BP 412 EP 415 DI 10.1097/INF.0b013e3181910e2d PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 439HY UT WOS:000265619400011 PM 19319022 ER PT J AU Havekes, B Romijn, JA Eisenhofer, G Adams, K Pacak, K AF Havekes, Bas Romijn, Johannes A. Eisenhofer, Graeme Adams, Karen Pacak, Karel TI Update on pediatric pheochromocytoma SO PEDIATRIC NEPHROLOGY LA English DT Review DE Pheochromocytoma; Paraganglioma; Genetics; Imaging; Positron emission tomography (PET); Children; Catecholamines; Metanephrines ID GENOTYPE-PHENOTYPE CORRELATIONS; ENDOCRINE NEOPLASIA TYPE-2; HIPPEL-LINDAU-DISEASE; BIOCHEMICAL-DIAGNOSIS; PLASMA METANEPHRINES; BLOOD-PRESSURE; I-123 METAIODOBENZYLGUANIDINE; MALIGNANT PHEOCHROMOCYTOMA; FAMILIAL PHEOCHROMOCYTOMA; PERIOPERATIVE MANAGEMENT AB Pheochromocytomas are rare tumors in children arising from chromaffin cells of adrenal medullary or extra-adrenal paraganglionic tissue. The tumors are characterized by synthesis, metabolism, and secretion of catecholamines. The formerly used guidelines for pheochromocytoma have been changed by recent discoveries, implementation of new approaches, and understanding of biochemistry, genetics, imaging, pathophysiology, and nomenclature of these tumors. In children, pheochromocytomas are more frequently familial, extra-adrenal, bilateral, and multifocal than in adults. Because of a highly variable clinical presentation, pheochromocytoma is often referred to as the great mimic. Measurements of plasma or urinary fractionated metanephrines are recommended as first-line biochemical tests for diagnosis, with optimum diagnostic sensitivity to be preferred over specificity. In general, localization studies must be used secondary to clinical and biochemical evidence. Adequate preoperative treatment with alpha-blockade is mandatory, including for pheochromocytomas that do not secrete but only synthesize catecholamines. Because approximately 40% of pheochromocytomas in children have a hereditary basis, proper genetic testing should be performed, with appropriate implications for future follow-up and treatment options. The risk for development of malignant disease depends highly on the underlying mutation, which may also impact recommendations concerning screening and surgical or systemic treatment. This article reviews recent advances in biochemistry, genetics, and imaging and outlines recommendations for improved evaluation and treatment of children with benign or malignant pheochromocytomas. C1 [Havekes, Bas; Adams, Karen; Pacak, Karel] NICHHD, Reprod Biol & Med Branch, Sect Med Neuroendocrinol, NIH, Bethesda, MD 20892 USA. [Havekes, Bas; Romijn, Johannes A.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab, Leiden, Netherlands. [Eisenhofer, Graeme] Univ Dresden, Dept Med, Dresden, Germany. [Eisenhofer, Graeme] Univ Dresden, Dept Clin Chem, Dresden, Germany. RP Pacak, K (reprint author), NICHHD, Reprod Biol & Med Branch, Sect Med Neuroendocrinol, NIH, Bldg 10,CRC,1-E,Room 1-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Intramural Research Program of the NIH/NICHD FX This research was supported in part by the Intramural Research Program of the NIH/NICHD. NR 66 TC 21 Z9 23 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD MAY PY 2009 VL 24 IS 5 BP 943 EP 950 DI 10.1007/s00467-008-0888-9 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 423ZQ UT WOS:000264535700003 PM 18566838 ER PT J AU Freeman, AF Holland, SM AF Freeman, Alexandra F. Holland, Steven M. TI Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes SO PEDIATRIC RESEARCH LA English DT Article ID HYPERIMMUNOGLOBULIN-E SYNDROME; RECURRENT-INFECTION SYNDROME; CORONARY-ARTERY ANEURYSMS; JOBS-SYNDROME; STAT3 MUTATIONS; IMMUNOGLOBULIN PRODUCTION; SIGNAL TRANSDUCER; ATOPIC-DERMATITIS; HOST-DEFENSE; B-CELLS AB Autosomal dominant Hyper-IgE syndrome (ADH-IES) is a rare primary immunodeficiency characterized by eczema, recurrent,skin and lung infections, elevated serum IgE, and various connective tissue, skeletal, and vascular abnormalities. Mutations in signal transducer and activator of transcription 3 (STAT3) have recently been found to account for most cases however, the pathogenesis of the varied features remains poorly defined. A distinct syndrome, known as autosomal recessive HIES (AR-HIES) manifests as severe eczema, recurrent bacterial and viral skin infections, and sinopulmonary infections. As opposed to STAT3 deficient HIES, AR-HIES lacks the connective tissue and skeletal manifestations but has an increase in neurologic abnormalities. In this review, we discuss the clinical presentations, genetic etiologies, and immunologic abnormalities of these two syndromes. In addition, we discuss animal models of STAT3 deficiency that provide insight into the pathogenesis of HIES. Further understanding of how STAT3 results in the diverse manifestations of HIES will allow us to develop more specific therapies for HIES as well as for many of the manifestations, such as scoliosis, recurrent staphylococcal infections, and eczema, which are common in the general population. (Pediatr Res 65: 32R-37R, 2009) C1 [Freeman, Alexandra F.] SAIC Frederick Inc, Lab Clin Infect Dis, Frederick, MD 21702 USA. [Holland, Steven M.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIH, Lab Clin Infect Dis, Bldg 10,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov FU National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX This research was supported by the National Institute of Allergy and Infectious Diseases. This project has been funded, in part. with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. NR 62 TC 39 Z9 44 U1 0 U2 5 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2009 VL 65 IS 5 BP 32R EP 37R PN 2 PG 6 WC Pediatrics SC Pediatrics GA 436XH UT WOS:000265448900006 PM 19190525 ER PT J AU Ananth, S Karunakaran, S Martin, P Nagineni, C Hooks, J Smith, S Prasad, P Ganapathy, V AF Ananth, Sudha Karunakaran, Senthil Martin, Pamela M. Nagineni, Chandrasekharam N. Hooks, John J. Smith, Sylvia B. Prasad, Puttur D. Ganapathy, Vadivel TI Functional Identification of a Novel Transport System for Endogenous and Synthetic Opioid Peptides in the Rabbit Conjunctival Epithelial Cell Line CJVE SO PHARMACEUTICAL RESEARCH LA English DT Article DE conjunctival epithelial cell; non-peptide opioid antagonists; opioid peptides; organic anion transporting polypeptides; transport process ID OCULAR SURFACE EPITHELIUM; DRUG-DELIVERY; HIGH-AFFINITY; GROWTH-FACTOR; POLYPEPTIDES; HOMEOSTASIS; EXPRESSION; OPIATES; BARRIER; FAMILY AB To investigate whether conjunctival epithelial cells express transport processes for opioid peptides. We monitored the uptake of [(3)H]deltorphin II and [(3)H]DADLE, two hydrolysis-resistant synthetic opioid peptides, in the rabbit conjunctival epithelial cell line CJVE and elucidated the characteristics of the uptake process. CJVE cells express robust uptake activity for deltorphin II and DADLE. Both opioid peptides compete with each other for transport. Several endogenous and synthetic opioid peptides, but not non-peptide opioid antagonists, are recognized by the transport process. Though various peptides inhibit the uptake of deltorphin II and DADLE in a similar manner, the uptake of deltorphin II is partly Na(+)-dependent whereas that of DADLE mostly Na(+)-independent. The transport process shows high affinity for many endogenous/synthetic opioid peptides. Functional features reveal that this transport process may be distinct from the opioid peptide transport system described in the retinal pigment epithelial cell line ARPE-19 and also from the organic anion transporting polypeptides, which are known to transport opioid peptides. CJVE cells express a novel, hitherto unknown transport process for endogenous/synthetic opioid peptides. This new transport process may offer an effective delivery route for opioid peptide drugs to the posterior segment of the eye. C1 [Ananth, Sudha; Karunakaran, Senthil; Martin, Pamela M.; Prasad, Puttur D.; Ganapathy, Vadivel] Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. [Nagineni, Chandrasekharam N.; Hooks, John J.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Smith, Sylvia B.; Ganapathy, Vadivel] Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. RP Ganapathy, V (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. EM vganapat@mcg.edu FU National Institutes of Health [DA 21560] FX This work was supported by the National Institutes of Health grant DA 21560. NR 33 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD MAY PY 2009 VL 26 IS 5 BP 1226 EP 1235 DI 10.1007/s11095-008-9709-x PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 428IS UT WOS:000264841800020 PM 18781380 ER PT J AU Panlilio, LV Thorndike, EB Schindler, CW AF Panlilio, Leigh V. Thorndike, Eric B. Schindler, Charles W. TI A stimulus-control account of dysregulated drug intake SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE Drug self-administration; Discrimination learning; Titration; Rats; Cocaine; Remifentanil; Food ID D-AMPHETAMINE; SET-POINT; COCAINE; RATS; TRANSITION; DISCRIMINATION; REINFORCEMENT; ESCALATION; SCHEDULES; BEHAVIOR AB Drug self-administration typically Occurs in a regular temporal pattern, with a consistent pause following each injection. We have proposed that this patterning results from differential reinforcement of post-injection pausing. In this view, even when every response produces an injection, some injections are not reinforcing because they occur when the level of drug effect is already maximal: consequently, drug reinforcement occurs on an intermittent schedule, and the interoceptive drug effect functions as a cue, indicating when another injection will be reinforcing. Previously, we emulated this situation with rats by using food reinforcement; each response was recorded as delivering a "virtual" injection. and a visual cue tracked the virtual drug level to indicate availability of reinforcement. This emulation schedule produced response patterns strikingly similar to actual drug self-administration. In the present study, the emulation schedule was modified to determine whether reinforcement of pausing is sufficient to produce these patterns, or whether a cue is necessary. Without a cue. response patterns were irregular and Virtual drug intake was escalated. These results suggest that a failure of interoceptive cues to control pausing might contribute to the dysregulated drug intake that is associated with addiction. Published by Elsevier Inc. C1 [Panlilio, Leigh V.; Thorndike, Eric B.; Schindler, Charles W.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Panlilio, LV (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM lpanlili@intra.nida.nih.gov FU NIH; National Institute on Drug Abuse FX This research was Supported by the Intramural Research Program of the NIH, National Institute on Drug Abuse. NR 20 TC 1 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2009 VL 92 IS 3 BP 439 EP 447 DI 10.1016/j.pbb.2009.01.011 PG 9 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 433CH UT WOS:000265180800009 PM 19463257 ER PT J AU Schmittner, J Schroeder, JR Epstein, DH Krantz, MJ Eid, NC Preston, KL AF Schmittner, John Schroeder, Jennifer R. Epstein, David H. Krantz, Mori J. Eid, Nicole C. Preston, Kenzie L. TI Electrocardiographic Effects of Lofexidine and Methadone Coadministration: Secondary Findings from a Safety Study SO PHARMACOTHERAPY LA English DT Article DE methadone; lofexidine; electrocardiogram; ECG; QTc interval ID STRESS-INDUCED REINSTATEMENT; QT PROLONGATION; DE-POINTES; INTERVAL; COCAINE; SEEKING; ACETYLMETHADOL; REPOLARIZATION; PENTAZOCINE; AGONISTS AB Study Objective. To determine the electrocardiographic effects of coadministration of lofexidine and methadone. Design. Prospective, double-blind study. Setting. Outpatient drug treatment research clinic. Participants. Fourteen adults (mean +/- SD age 34.9 +/- 5.3 yrs) with physical dependence on opioids. Intervention. Participants were stabilized on methadone maintenance therapy, reaching a target dose of 80 mg/day After 3 weeks of methadone stabilization, participants received lofexidine 0.4 mg or placebo once/day, each for I week, administered at the same time as methadone. From weeks 3-8, all subjects received lofexidine, with the dose escalated each week in 0.2-mg increments so that by week 8, participants were receiving lorexidine 1.6 mg/day Electrocardiograms (ECGs) were obtained at baseline (before methadone), after stabilization with methadone, and after lofexidine coadministration during peak plasma lofexidine levels. Measurements and Main Results. Prespecified outcome measures of mean and maximal changes in heart rate, and PR, QRS, and QTc intervals were obtained after stabilization with methadone and after lofexidine 0.4 mg coadministration. Repeated-measures regression showed no significant changes in heart rate or PR, QRS, or QTc interval after methadone stabilization, but a significant decrease in heart rate (mean +/- SD -8.0 +/- 7.3 beats/min, p=0.0006) after starting lofexidine. When data were analyzed by using maximal ECG response, again, no significant changes were noted during methadone induction compared with baseline, but significant changes did occur in all four ECG parameters when lofexidine was coadministered: decreased heart rate (mean +/- SD -9.6 +/- 5.8 beats/min, p<0.0001) and increased PR interval (+11.1 +/- 19.8 msec, p=0.026), QRS interval (+3.7 +/- 4.3 msec, p=0.002), and QTc interval (+21.9 +/- 40.8 msec, p=0.01.8). In three female participants, the change in QTc interval from baseline was clinically significant (> 40 msec). Conclusion. Our preliminary data suggest that coadministration of lofexidine and methadone induces QTc interval prolongation. This drug combination should be prescribed cautiously, with ECG monitoring. Furthermore, because the participants with the largest changes in QTc interval in our study were female, women may be at highest risk. C1 [Schmittner, John; Epstein, David H.; Eid, Nicole C.; Preston, Kenzie L.] NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Krantz, Mori J.] Univ Colorado, Sch Med, Div Cardiol, Denver, CO USA. [Krantz, Mori J.] Colorado Prevent Ctr, Denver, CO USA. RP Preston, KL (reprint author), NIDA, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural Research Program; National Institute on Drug Abuse; National Institutes of Health; U.S. Department of Health and Human Services FX Supported by funding from the Intramural Research Program, National Institute on Drug Abuse. National Institutes of Health, U.S. Department of Health and Human Services. Lofexidinc and matching placebo were provided by Forum Products, Inc., Redhill Surry United Kingdom. NR 27 TC 8 Z9 8 U1 0 U2 1 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY PY 2009 VL 29 IS 5 BP 495 EP 502 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 440AZ UT WOS:000265671500002 PM 19397459 ER PT J AU Church, DM Goodstadt, L Hillier, LW Zody, MC Goldstein, S She, XW Bult, CJ Agarwala, R Cherry, JL DiCuccio, M Hlavina, W Kapustin, Y Meric, P Maglott, D Birtle, Z Marques, AC Graves, T Zhou, SG Teague, B Potamousis, K Churas, C Place, M Herschleb, J Runnheim, R Forrest, D Amos-Landgraf, J Schwartz, DC Cheng, Z Lindblad-Toh, K Eichler, EE Ponting, CP AF Church, Deanna M. Goodstadt, Leo Hillier, LaDeana W. Zody, Michael C. Goldstein, Steve She, Xinwe Bult, Carol J. Agarwala, Richa Cherry, Joshua L. DiCuccio, Michael Hlavina, Wratko Kapustin, Yuri Meric, Peter Maglott, Donna Birtle, Zoe Marques, Ana C. Graves, Tina Zhou, Shiguo Teague, Brian Potamousis, Konstantinos Churas, Christopher Place, Michael Herschleb, Jill Runnheim, Ron Forrest, Daniel Amos-Landgraf, James Schwartz, David C. Cheng, Ze Lindblad-Toh, Kerstin Eichler, Evan E. Ponting, Chris P. CA Mouse Genome Sequencing Consortium TI Lineage-Specific Biology Revealed by a Finished Genome Assembly of the Mouse SO PLOS BIOLOGY LA English DT Article ID RECENT SEGMENTAL DUPLICATIONS; RADIATION HYBRID MAP; PSEUDOAUTOSOMAL REGION; MONODELPHIS-DOMESTICA; CYTOPLASMIC PROTEIN; MAMMALIAN EVOLUTION; HUMAN-DISEASE; X-CHROMOSOME; Y-CHROMOSOME; GENE FAMILY AB The mouse (Mus musculus) is the premier animal model for understanding human disease and development. Here we show that a comprehensive understanding of mouse biology is only possible with the availability of a finished, high-quality genome assembly. The finished clone-based assembly of the mouse strain C57BL/6J reported here has over 175,000 fewer gaps and over 139 Mb more of novel sequence, compared with the earlier MGSCv3 draft genome assembly. In a comprehensive analysis of this revised genome sequence, we are now able to define 20,210 protein-coding genes, over a thousand more than predicted in the human genome (19,042 genes). In addition, we identified 439 long, non-proteincoding RNAs with evidence for transcribed orthologs in human. We analyzed the complex and repetitive landscape of 267 Mb of sequence that was missing or misassembled in the previously published assembly, and we provide insights into the reasons for its resistance to sequencing and assembly by whole-genome shotgun approaches. Duplicated regions within newly assembled sequence tend to be of more recent ancestry than duplicates in the published draft, correcting our initial understanding of recent evolution on the mouse lineage. These duplicates appear to be largely composed of sequence regions containing transposable elements and duplicated protein-coding genes; of these, some may be fixed in the mouse population, but at least 40% of segmentally duplicated sequences are copy number variable even among laboratory mouse strains. Mouse lineage-specific regions contain 3,767 genes drawn mainly from rapidly-changing gene families associated with reproductive functions. The finished mouse genome assembly, therefore, greatly improves our understanding of rodent-specific biology and allows the delineation of ancestral biological functions that are shared with human from derived functions that are not. C1 [Church, Deanna M.; Agarwala, Richa; Cherry, Joshua L.; DiCuccio, Michael; Hlavina, Wratko; Kapustin, Yuri; Meric, Peter; Maglott, Donna] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Goodstadt, Leo; Birtle, Zoe; Marques, Ana C.; Ponting, Chris P.] Univ Oxford, Dept Physiol Anat & Genet, MRC Funct Genom Unit, Oxford, England. [Hillier, LaDeana W.; Graves, Tina] Washington Univ, Genome Ctr, St Louis, MO USA. [Zody, Michael C.; Lindblad-Toh, Kerstin] Broad Inst MIT & Harvard, Cambridge, MA USA. [Zody, Michael C.; Lindblad-Toh, Kerstin] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden. [Goldstein, Steve; Zhou, Shiguo; Teague, Brian; Potamousis, Konstantinos; Churas, Christopher; Herschleb, Jill; Runnheim, Ron; Forrest, Daniel; Schwartz, David C.] Univ Wisconsin Madison, Lab Mol & Computat Genom, Madison, WI USA. [She, Xinwe; Cheng, Ze; Eichler, Evan E.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [She, Xinwe; Cheng, Ze; Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Bult, Carol J.] Jackson Lab, Bar Harbor, ME 04609 USA. [Place, Michael] Univ Wisconsin Madison, Waisman Ctr, Madison, WI USA. [Amos-Landgraf, James] Univ Wisconsin, McArdle Lab Canc Res, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Church, DM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM church@ncbi.nlm.nih.gov; plos@llew.org.uk; kersli@broad.mit.edu; eee@gs.washington.edu; chris.ponting@dpag.ox.ac.uk RI Zhou, Shiguo/B-3832-2011; Amos-Landgraf, James/K-9288-2013; OI Zhou, Shiguo/0000-0001-7421-2506; Amos-Landgraf, James/0000-0003-2535-7746; Marques, Ana Claudia/0000-0001-5174-8092; McCombie, W. Richard/0000-0003-1899-0682; Stubbs, Lisa/0000-0002-9556-1972; Ponting, Chris/0000-0003-0202-7816 FU National Institutes of Health Intramural Sequencing Center; UK Medical Research Council; Swiss National Science Foundation; National Institutes of Health [HG002385]; National Human Genome Research Institute; Wellcome Trust FX DMC, RA, JC, MD, DM, WH, YK, and the National Institutes of Health Intramural Sequencing Center were supported by the Intramural Research Program of the NIH. CPP, ZB, and LG were supported by the UK Medical Research Council. ACM was supported by the Swiss National Science Foundation. EEE, XS, and ZC were supported in part by National Institutes of Health grant HG002385. EEE is an investigator of the Howard Hughes Medical Institute. The Genome Center at Washington University, The Human Genome Sequencing Center at the Baylor College of Medicine, and The Broad Institute of Harvard and MIT are supported by genome sequencing grants from National Human Genome Research Institute. Chromosomes 2, 4, 11 and X were completed with funding from the Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 214 Z9 4774 U1 6 U2 92 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAY PY 2009 VL 7 IS 5 AR e1000112 DI 10.1371/journal.pbio.1000112 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 461PY UT WOS:000267282000011 PM 19468303 ER PT J AU Pries, AR Cornelissen, AJM Sloot, AA Hinkeldey, M Dreher, MR Hopfner, M Dewhirst, MW Secomb, TW AF Pries, Axel R. Cornelissen, Annemiek J. M. Sloot, Anoek A. Hinkeldey, Marlene Dreher, Matthew R. Hoepfner, Michael Dewhirst, Mark W. Secomb, Timothy W. TI Structural Adaptation and Heterogeneity of Normal and Tumor Microvascular Networks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID BLOOD-FLOW; ANTIANGIOGENIC THERAPY; INDUCED ANGIOGENESIS; MATHEMATICAL-MODEL; VASCULAR SYSTEM; SKELETAL-MUSCLE; GROWTH; NORMALIZATION; COMMUNICATION; RESISTANCE AB Relative to normal tissues, tumor microcirculation exhibits high structural and functional heterogeneity leading to hypoxic regions and impairing treatment efficacy. Here, computational simulations of blood vessel structural adaptation are used to explore the hypothesis that abnormal adaptive responses to local hemodynamic and metabolic stimuli contribute to aberrant morphological and hemodynamic characteristics of tumor microcirculation. Topology, vascular diameter, length, and red blood cell velocity of normal mesenteric and tumor vascular networks were recorded by intravital microscopy. Computational models were used to estimate hemodynamics and oxygen distribution and to simulate vascular diameter adaptation in response to hemodynamic, metabolic and conducted stimuli. The assumed sensitivity to hemodynamic and conducted signals, the vascular growth tendency, and the random variability of vascular responses were altered to simulate 'normal' and 'tumor' adaptation modes. The heterogeneous properties of vascular networks were characterized by diameter mismatch at vascular branch points (d(var)(3)) and deficit of oxygen delivery relative to demand (O(2def)). In the tumor, d(var)(3) and O(2def) were higher (0.404 and 0.182) than in normal networks (0.278 and 0.099). Simulated remodeling of the tumor network with 'normal' parameters gave low values (0.288 and 0.099). Conversely, normal networks attained tumor-like characteristics (0.41 and 0.179) upon adaptation with 'tumor' parameters, including low conducted sensitivity, increased growth tendency, and elevated random biological variability. It is concluded that the deviant properties of tumor microcirculation may result largely from defective structural adaptation, including strongly reduced responses to conducted stimuli. C1 [Pries, Axel R.; Cornelissen, Annemiek J. M.; Hinkeldey, Marlene; Hoepfner, Michael] Charite Univ Med Berlin, Dept Physiol, Berlin, Germany. [Pries, Axel R.] Deutsch Herzzentrum Berlin, Berlin, Germany. [Cornelissen, Annemiek J. M.] CNRS, Lab Matiere & Syst Complexes MSC, UMR 7057, Paris, France. [Cornelissen, Annemiek J. M.] Univ Paris Diderot, Paris, France. [Sloot, Anoek A.] Delft Univ Technol, Fac Mech Engn & Marine Technol, Dept Man Machine Syst, Delft, Netherlands. [Dreher, Matthew R.] NIH, Clin Ctr Radiol & Imaging SCi, Bethesda, MD 20892 USA. [Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Secomb, Timothy W.] Univ Arizona, Dept Physiol, Tucson, AZ USA. RP Pries, AR (reprint author), Charite Univ Med Berlin, Dept Physiol, Berlin, Germany. EM secomb@u.arizona.edu OI Secomb, Timothy/0000-0002-0176-5502 FU National Institutes of Health [CA040355, HL034555]; European Commission (Marie Curie Individual Fellowship) [MCFI-2001-01930]; Dutch Cancer Society FX This work was supported by National Institutes of Health grants CA040355 and HL034555, a grant from the European Commission (Marie Curie Individual Fellowship No MCFI-2001-01930 to AJM Cornelissen) and the Dutch Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 64 Z9 67 U1 2 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2009 VL 5 IS 5 AR e1000394 DI 10.1371/journal.pcbi.1000394 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 459DT UT WOS:000267081300007 PM 19478883 ER PT J AU Rzhetsky, A Shatkay, H Wilbur, WJ AF Rzhetsky, Andrey Shatkay, Hagit Wilbur, W. John TI How to Get the Most out of Your Curation Effort SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID BIOMEDICAL TEXT; DATABASE AB Large-scale annotation efforts typically involve several experts who may disagree with each other. We propose an approach for modeling disagreements among experts that allows providing each annotation with a confidence value (i.e., the posterior probability that it is correct). Our approach allows computing certainty-level for individual annotations, given annotator-specific parameters estimated from data. We developed two probabilistic models for performing this analysis, compared these models using computer simulation, and tested each model's actual performance, based on a large data set generated by human annotators specifically for this study. We show that even in the worst-case scenario, when all annotators disagree, our approach allows us to significantly increase the probability of choosing the correct annotation. Along with this publication we make publicly available a corpus of 10,000 sentences annotated according to several cardinal dimensions that we have introduced in earlier work. The 10,000 sentences were all 3-fold annotated by a group of eight experts, while a 1,000-sentence subset was further 5-fold annotated by five new experts. While the presented data represent a specialized curation task, our modeling approach is general; most data annotation studies could benefit from our methodology. C1 [Rzhetsky, Andrey] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Rzhetsky, Andrey] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Rzhetsky, Andrey] Univ Chicago, Computat Inst, Chicago, IL 60637 USA. [Rzhetsky, Andrey] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Shatkay, Hagit] Queens Univ, Sch Comp, Computat Biol & Machine Learning Lab, Kingston, ON, Canada. [Wilbur, W. John] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Rzhetsky, A (reprint author), Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM arzhetsky@uchicago.edu RI rzhetsky, andrey/B-6118-2012; OI Rzhetsky, Andrey/0000-0001-6959-7405 FU National Institutes of Health [GM61372]; National Science Foundation [0438291, 0121687]; Cure Autism Now Foundation; National Library of Medicine FX This work was supported by the National Institutes of Health (GM61372 to AR), the National Science Foundation (0438291 and 0121687 to AR), and the Cure Autism Now Foundation. WJW is supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The funding agencies did not influence the manuscript preparation or its scientific content. NR 18 TC 12 Z9 12 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2009 VL 5 IS 5 AR e1000391 DI 10.1371/journal.pcbi.1000391 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 459DT UT WOS:000267081300011 PM 19461884 ER PT J AU Cheng, CY Kao, WHL Patterson, N Tandon, A Haiman, CA Harris, TB Xing, C John, EM Ambrosone, CB Brancati, FL Coresh, J Press, MF Parekh, RS Klag, MJ Meoni, LA Hsueh, WC Fejerman, L Pawlikowska, L Freedman, ML Jandorf, LH Bandera, EV Ciupak, GL Nalls, MA Akylbekova, EL Orwoll, ES Leak, TS Miljkovic, I Li, RL Ursin, G Bernstein, L Ardlie, K Taylor, HA Boerwinckle, E Zmuda, JM Henderson, BE Wilson, JG Reich, D AF Cheng, Ching-Yu Kao, W. H. Linda Patterson, Nick Tandon, Arti Haiman, Christopher A. Harris, Tamara B. Xing, Chao John, Esther M. Ambrosone, Christine B. Brancati, Frederick L. Coresh, Josef Press, Michael F. Parekh, Rulan S. Klag, Michael J. Meoni, Lucy A. Hsueh, Wen-Chi Fejerman, Laura Pawlikowska, Ludmila Freedman, Matthew L. Jandorf, Lina H. Bandera, Elisa V. Ciupak, Gregory L. Nalls, Michael A. Akylbekova, Ermeg L. Orwoll, Eric S. Leak, Tennille S. Miljkovic, Iva Li, Rongling Ursin, Giske Bernstein, Leslie Ardlie, Kristin Taylor, Herman A. Boerwinckle, Eric Zmuda, Joseph M. Henderson, Brian E. Wilson, James G. Reich, David TI Admixture Mapping of 15,280 African Americans Identifies Obesity Susceptibility Loci on Chromosomes 5 and X SO PLOS GENETICS LA English DT Article ID GENOME-WIDE SCAN; BODY-WEIGHT; FTO GENE; CART GENE; UNITED-STATES; DISEASE GENES; FAT MASS; ASSOCIATION; VARIANTS; RISK AB The prevalence of obesity (body mass index (BMI) >= 30 kg/m(2)) is higher in African Americans than in European Americans, even after adjustment for socioeconomic factors, suggesting that genetic factors may explain some of the difference. To identify genetic loci influencing BMI, we carried out a pooled analysis of genome-wide admixture mapping scans in 15,280 African Americans from 14 epidemiologic studies. Samples were genotyped at a median of 1,411 ancestry-informative markers. After adjusting for age, sex, and study, BMI was analyzed both as a dichotomized (top 20% versus bottom 20%) and a continuous trait. We found that a higher percentage of European ancestry was significantly correlated with lower BMI (rho = -0.042, P = 1.6 x 10(-7)). In the dichotomized analysis, we detected two loci on chromosome X as associated with increased African ancestry: the first at Xq25 (locus-specific LOD = 5.94; genome-wide score = 3.22; case-control Z = -3.94); and the second at Xq13.1 (locus-specific LOD = 2.22; case-control Z = -4.62). Quantitative analysis identified a third locus at 5q13.3 where higher BMI was highly significantly associated with greater European ancestry (locus-specific LOD = 6.27; genome-wide score = 3.46). Further mapping studies with dense sets of markers will be necessary to identify the alleles in these regions of chromosomes X and 5 that may be associated with variation in BMI. C1 [Cheng, Ching-Yu; Kao, W. H. Linda; Brancati, Frederick L.; Coresh, Josef; Klag, Michael J.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Cheng, Ching-Yu] Natl Yang Ming Univ, Sch Med, Dept Ophthalmol, Taipei 112, Taiwan. [Cheng, Ching-Yu] Taipei Vet Gen Hosp, Taipei, Taiwan. [Kao, W. H. Linda; Brancati, Frederick L.; Coresh, Josef] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Patterson, Nick; Tandon, Arti; Freedman, Matthew L.; Ardlie, Kristin; Reich, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Tandon, Arti; Reich, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Haiman, Christopher A.; Ursin, Giske; Bernstein, Leslie; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Harris, Tamara B.; Nalls, Michael A.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Xing, Chao] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Xing, Chao] Univ Texas SW Med Ctr Dallas, McDermott Ctr Human Growth & Dev, Dallas, TX 75390 USA. [Xing, Chao] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. [John, Esther M.] No Calif Canc Ctr, Fremont, CA USA. [John, Esther M.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [John, Esther M.] Stanford Canc Ctr, Stanford, CA USA. [Ambrosone, Christine B.; Ciupak, Gregory L.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Parekh, Rulan S.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. [Parekh, Rulan S.; Klag, Michael J.; Meoni, Lucy A.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. [Klag, Michael J.] Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. [Meoni, Lucy A.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. [Hsueh, Wen-Chi; Fejerman, Laura] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Fejerman, Laura; Pawlikowska, Ludmila] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Fejerman, Laura] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Pawlikowska, Ludmila] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jandorf, Lina H.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. [Bandera, Elisa V.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ USA. [Nalls, Michael A.] NIA, Mol Genet Sect, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. [Akylbekova, Ermeg L.] Jackson State Univ, Jackson Heart Study Anal Grp, Jackson, MS USA. [Orwoll, Eric S.] Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97201 USA. [Leak, Tennille S.; Miljkovic, Iva; Zmuda, Joseph M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Li, Rongling] Univ Tennessee, Dept Prevent Med, Div Biostat & Epidemiol, Memphis, TN USA. [Ursin, Giske] Univ Oslo, Dept Nutr, Oslo, Norway. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Canc Etiol, Div Populat Sci, Duarte, CA 91010 USA. [Ardlie, Kristin] Genom Collaborat, Cambridge, MA USA. [Taylor, Herman A.] Jackson State Univ, Jackson, MS USA. [Taylor, Herman A.] Tougaloo Coll, Tougaloo, MS USA. [Taylor, Herman A.; Wilson, James G.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Boerwinckle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Wilson, James G.] GV Sonny Montgomery Vet Affairs Med Ctr, Jackson, MS USA. RP Cheng, CY (reprint author), Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. EM cycheng@jhsph.edu; wkao@jhsph.edu; reich@genetics.med.harvard.edu RI Cheng, Ching-Yu/K-7017-2013; Bandera, Elisa/M-4169-2014; OI Cheng, Ching-Yu/0000-0003-0655-885X; Bandera, Elisa/0000-0002-8789-2755; Miljkovic, Iva/0000-0002-3155-9777; Fejerman, Laura/0000-0003-3179-1151; Orwoll, Eric/0000-0002-8520-7355 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R21DK073482, Kol DK067207, N01-HC-95170, N01-HC-95171, N01-HC-95172]; National Cancer Institute (NCI), National Institutes of Health (NIH) [RFA-CA-06-503, N01-CO-12400]; Northern California BCFR site [U01 CA6941 7]; National Institute of Child Health and Human Development [NOl-HD-3-31 75]; NCI [NOl-PC-6701 0, CA 74847, CA63464, R01-CA100598]; California Department of Health Services [OSOG 8709]; National Institute of Environmental Health Sciences [R01-ES-07084]; California Breast Cancer Research Program [PB-0051]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U01 DK070657, U01DK57304, K01DK067207, U01DK57292]; National Center for Research Resources; National Center on Minority Health and Health Disparities; United States Army Medical Research Program; Center of Excellence for Biobehavioral Breast Cancer Research [DAMD17-01-1-0334]; Susan Komen Foundation for Breast Cancer Research [KG080165]; Burroughs Wellcome Career Development Award in the Biomedical Sciences [U01-HG0041]; [RL-1 HL092550]; [U54-RR020278]; [CA 17054]; [4PB-0092]; [CA54281]; [U01 AR45580]; [U01 AR45614]; [U01 AR45632]; [U01 AR45647]; [U01 AR45654]; [U01 AR45583]; [U01 AG18197]; [U01-AG027810]; [ULl RR024140]; [R01-AR051124]; [R01-CA63446]; [R01-CA77305]; [DAMD1 7-96-607]; [7PB-0068]; [AG05407]; [AG05394]; [AR35584]; [AR35583]; [5T32AG0001 81-19] FX The ARIC Study was carried out as a collaborative study supported by the National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021 and N01-HC-55022 with support for this analysis by R21DK073482 and Kol DK067207 (WHLK). The BCFR was supported by the National Cancer Institute (NCI), National Institutes of Health (NIH) under RFA-CA-06-503 and through cooperative agreements with members of the BCFR and PIs. The Northern California BCFR site was funded by U01 CA6941 7. The Los Angeles component of the Women's Contraceptive and Reproductive Experiences study received support from contracts with the National Institute of Child Health and Human Development (NOl -HD-3-31 75), the NCI (NOl-PC-6701 0) and the California Department of Health Services (OSOG 8709), and grants from the National Institute of Environmental Health Sciences (R01-ES-07084) and the California Breast Cancer Research Program (PB-0051). The DHS was supported by the Donald W. Reynolds Foundation and grant 1 RL-1 HL092550 from the NIH. The FIND Study included in this analysis was supported by the following research grants: U01 DK070657, U01DK57304, K01DK067207 (WHLK), and U01DK57292 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and, in part, by the Intramural Research Program of the NIDDK; this research was supported in part by the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and has been funded in part with federal funds from the NCI, NIH, under contract N01-CO-12400. Research support for Health ABC was provided by the Intramural Research Program of the National Institute on Aging, and contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. Genotyping in Health ABC was supported by National Center for Research Resources grant U54-RR020278. Research support for JHS studies was provided by R01-HL084107 (JGW) from the NHLBI and contracts N01-HC-95170, N01-HC-95171, and N01-HC-95172 from the NHLBI and the National Center on Minority Health and Health Disparities. The LIFE Study was supported by grants CA 17054, CA 74847 from the NCI, and by grant 4PB-0092 from the California Breast Cancer Research Program of the University of California. The MEC Study was supported by NCI grants CA63464 and CA54281. MrOS is supported by grants: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, ULl RR024140 and R01-AR051124. SFBABCS was supported by grants R01-CA63446 and R01-CA77305 from the NCI, grant DAMD1 7-96-607 from the United States Army Medical Research Program, and grant 7PB-0068 from the California Breast Cancer Research Program. SOF was supported by grants AG05407, AR35582, AG05394, AR35584, and AR35583. The WCHS was initially funded as part of a Center of Excellence for Biobehavioral Breast Cancer Research (United States Army Medical Research Program, DAMD17-01-1-0334) and subsequently by R01-CA100598 from the NCI. Genotyping for SFBABCS and WCHS was supported by grant KG080165 from the Susan Komen Foundation for Breast Cancer Research. DR was supported by a Burroughs Wellcome Career Development Award in the Biomedical Sciences, and methodological work was supported by grant U01-HG0041 68 to DR, NP and AT. TL is postdoctoral fellow funded on 5T32AG0001 81-19, Training in the Epidemiology of Aging. NR 50 TC 45 Z9 45 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2009 VL 5 IS 5 AR e1000490 DI 10.1371/journal.pgen.1000490 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 459EH UT WOS:000267083000012 PM 19461885 ER PT J AU Dave, UP Akagi, K Tripathi, R Cleveland, SM Thompson, MA Yi, M Stephens, R Downing, JR Jenkins, NA Copeland, NG AF Dave, Utpal P. Akagi, Keiko Tripathi, Rati Cleveland, Susan M. Thompson, Mary A. Yi, Ming Stephens, Robert Downing, James R. Jenkins, Nancy A. Copeland, Neal G. TI Murine Leukemias with Retroviral Insertions at Lmo2 Are Predictive of the Leukemias Induced in SCID-X1 Patients Following Retroviral Gene Therapy SO PLOS GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; T-CELL DEVELOPMENT; VECTOR INTEGRATION; CANCER GENES; EXPRESSION; MUTAGENESIS; TRANSCRIPTION; LYMPHOMAS; TRANSLOCATION AB Five X-linked severe combined immunodeficiency patients (SCID-X1) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy. C1 [Dave, Utpal P.; Tripathi, Rati; Cleveland, Susan M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37203 USA. [Dave, Utpal P.; Tripathi, Rati; Cleveland, Susan M.] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN USA. [Akagi, Keiko] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Thompson, Mary A.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Yi, Ming; Stephens, Robert] Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD USA. [Downing, James R.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 117548, Singapore. RP Dave, UP (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37203 USA. EM utpal.dave@vanderbilt.edu RI ASTAR, IMCB/E-2320-2012 FU American Cancer Society institutional [IRG-58-009-48]; Sartain-Lanier Family Foundation; T. J. Martell Foundation; Hope Street Kids; Vanderbilt Physician Scientist Development; National Heart, Lung and Blood Institute [1K08HL089403-01]; National Cancer Institute [5T32CA009385-25]; Vanderbilt Ingram Cancer Center [P30 CA68485]; Vanderbilt Digestive Disease Center [P30 DK58404]; Vanderbilt Vision Center [P30 EY08126] FX This work was supported by the American Cancer Society institutional grant (#IRG-58-009-48), the Sartain-Lanier Family Foundation, the T. J. Martell Foundation, and Hope Street Kids to UPD. UPD was also supported by a Vanderbilt Physician Scientist Development award and the National Heart, Lung and Blood Institute grant 1K08HL089403-01. SMC was supported by a training grant from the National Cancer Institute 5T32CA009385-25. All microarray experiments were performed in the Vanderbilt Microarray Shared Resource, which is supported by the Vanderbilt Ingram Cancer Center (P30 CA68485), the Vanderbilt Digestive Disease Center (P30 DK58404) and the Vanderbilt Vision Center (P30 EY08126). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 51 Z9 51 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2009 VL 5 IS 5 AR e1000491 DI 10.1371/journal.pgen.1000491 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 459EH UT WOS:000267083000013 PM 19461887 ER PT J AU Dronamraju, R Mason, JM AF Dronamraju, Raghuvar Mason, James M. TI Recognition of Double Strand Breaks by a Mutator Protein (MU2) in Drosophila melanogaster SO PLOS GENETICS LA English DT Article ID DNA-DAMAGE RESPONSE; PHOSPHORYLATED HISTONE H2AX; SACCHAROMYCES-CEREVISIAE; CELL-LINES; MDC1; CHROMOSOMES; CHECKPOINT; EXPRESSION; CHROMATIN; PATHWAYS AB Telomere capture, a rare event that stabilizes chromosome breaks, is associated with certain genetic abnormalities in humans. Studies pertaining to the generation, maintenance, and biological effects of telomere formation are limited in metazoans. A mutation, mu2(a), in Drosophila melanogaster decreases the rate of repair of double strand DNA breaks in oocytes, thus leading to chromosomes that have lost a natural telomere and gained a new telomere. Amino acid sequence, domain architecture, and protein interactions suggest that MU2 is an ortholog of human MDC1. The MU2 protein is a component of meiotic recombination foci and localizes to repair foci in S2 cells after irradiation in a manner similar to that of phosphorylated histone variant H2Av. Domain searches indicated that the protein contains an N-terminal FHA domain and a C-terminal tandem BRCT domain. Peptide pull-down studies showed that the BRCT domain interacts with phosphorylated H2Av, while the FHA domain interacts with the complex of MRE11, RAD50, and NBS. A frameshift mutation that eliminates the MU2 BRCT domain decreases the number and size of meiotic phospho-H2Av foci. MU2 is also required for the intra-S checkpoint in eye-antennal imaginal discs. MU2 participates at an early stage in the recognition of DNA damage at a step that is prerequisite for both DNA repair and cell cycle checkpoint control. We propose a model suggesting that neotelomeres may arise when radiation-induced chromosome breaks fail to be repaired, fail to arrest progression through meiosis, and are deposited in the zygote, where cell cycle control is absent and rapid rounds of replication and telomere formation ensue. C1 [Dronamraju, Raghuvar; Mason, James M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Dronamraju, R (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. EM masonj@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [ES021054] FX work was funded by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, ES021054. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 17 Z9 18 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2009 VL 5 IS 5 AR e1000473 DI 10.1371/journal.pgen.1000473 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 459EH UT WOS:000267083000028 PM 19424425 ER PT J AU Noureddine, MA Menendez, D Campbell, MR Bandele, OJ Horvath, MM Wang, XT Pittman, GS Chorley, BN Resnick, MA Bell, DA AF Noureddine, Maher A. Menendez, Daniel Campbell, Michelle R. Bandele, Omari J. Horvath, Monica M. Wang, Xuting Pittman, Gary S. Chorley, Brian N. Resnick, Michael A. Bell, Douglas A. TI Probing the Functional Impact of Sequence Variation on p53-DNA Interactions Using a Novel Microsphere Assay for Protein-DNA Binding with Human Cell Extracts SO PLOS GENETICS LA English DT Article ID P53 TRANSCRIPTIONAL NETWORK; GENE-EXPRESSION; HUMAN GENOME; REGULATORY NETWORK; RESPONSE ELEMENTS; PROMOTER REGION; SITE; IDENTIFICATION; DAMAGE; STRESS AB The p53 tumor suppressor regulates its target genes through sequence-specific binding to DNA response elements (REs). Although numerous p53 REs are established, the thousands more identified by bioinformatics are not easily subjected to comparative functional evaluation. To examine the relationship between RE sequence variation-including polymorphisms-and p53 binding, we have developed a multiplex format microsphere assay of protein-DNA binding (MAPD) for p53 in nuclear extracts. Using MAPD we measured sequence-specific p53 binding of doxorubicin-activated or transiently expressed p53 to REs from established p53 target genes and p53 consensus REs. To assess the sensitivity and scalability of the assay, we tested 16 variants of the p21 target sequence and a 62-multiplex set of single nucleotide (nt) variants of the p53 consensus sequence and found many changes in p53 binding that are not captured by current computational binding models. A group of eight single nucleotide polymorphisms (SNPs) was examined and binding profiles closely matched transactivation capability tested in luciferase constructs. The in vitro binding characteristics of p53 in nuclear extracts recapitulated the cellular in vivo transactivation capabilities for eight well-established human REs measured by luciferase assay. Using a set of 26 bona fide REs, we observed distinct binding patterns characteristic of transiently expressed wild type and mutant p53s. This microsphere assay system utilizes biologically meaningful cell extracts in a multiplexed, quantitative, in vitro format that provides a powerful experimental tool for elucidating the functional impact of sequence polymorphism and protein variation on protein/DNA binding in transcriptional networks. C1 [Noureddine, Maher A.; Campbell, Michelle R.; Bandele, Omari J.; Horvath, Monica M.; Wang, Xuting; Pittman, Gary S.; Chorley, Brian N.; Bell, Douglas A.] Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, Res Triangle Pk, NC USA. [Menendez, Daniel; Resnick, Michael A.] Natl Inst Environm Hlth Sci, Chromosome Stabil Grp, Mol Genet Lab, Res Triangle Pk, NC USA. RP Noureddine, MA (reprint author), Natl Inst Environm Hlth Sci, Environm Genom Grp, Mol Genet Lab, Res Triangle Pk, NC USA. EM BELL1@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU National Institute of Environmental Health Sciences; National Institutes of Health [Z01-ES-100475-M-0001, Z01 ES065079-15] FX This research was funded entirely by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (projects: Z01-ES-100475-M-0001 and Z01 ES065079-15). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 52 TC 25 Z9 25 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD MAY PY 2009 VL 5 IS 5 AR e1000462 DI 10.1371/journal.pgen.1000462 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 459EH UT WOS:000267083000021 PM 19424414 ER PT J AU Lott, ST Chen, NY Chandler, DS Yang, QF Wang, L Rodriguez, M Xie, HY Balasenthil, S Buchholz, TA Sahin, AA Chaung, K Zhang, BL Olufemi, SE Chen, JY Adams, H Band, V El-Naggar, AK Frazier, ML Keyomarsi, K Hunt, KK Sen, S Haffty, B Hewitt, SM Krahe, R Killary, AM AF Lott, Steven T. Chen, Nanyue Chandler, Dawn S. Yang, Qifeng Wang, Luo Rodriguez, Marivonne Xie, Hongyan Balasenthil, Seetharaman Buchholz, Thomas A. Sahin, Aysegul A. Chaung, Katrina Zhang, Baili Olufemi, Shodimu-Emmanu Chen, Jinyun Adams, Henry Band, Vimla El-Naggar, Adel K. Frazier, Marsha L. Keyomarsi, Khandan Hunt, Kelly K. Sen, Subrata Haffty, Bruce Hewitt, Stephen M. Krahe, Ralf Killary, Ann McNeill TI DEAR1 Is a Dominant Regulator of Acinar Morphogenesis and an Independent Predictor of Local Recurrence-Free Survival in Early-Onset Breast Cancer SO PLOS MEDICINE LA English DT Article ID TUMOR-SUPPRESSOR LOCUS; RENAL-CELL CARCINOMA; FAMILIAL MEDITERRANEAN FEVER; ACUTE PROMYELOCYTIC LEUKEMIA; CHROMOSOME 3P12; MAMMARY TUMORIGENESIS; PROGNOSTIC-FACTOR; EPITHELIAL ACINI; YOUNG AGE; IN-VIVO AB Background: Breast cancer in young women tends to have a natural history of aggressive disease for which rates of recurrence are higher than in breast cancers detected later in life. Little is known about the genetic pathways that underlie early-onset breast cancer. Here we report the discovery of DEAR1 (ductal epithelium-associated RING Chromosome 1), a novel gene encoding a member of the TRIM (tripartite motif) subfamily of RING finger proteins, and provide evidence for its role as a dominant regulator of acinar morphogenesis in the mammary gland and as an independent predictor of local recurrence-free survival in early-onset breast cancer. Methods and Findings: Suppression subtractive hybridization identified DEAR1 as a novel gene mapping to a region of high-frequency loss of heterozygosity (LOH) in a number of histologically diverse human cancers within Chromosome 1p35.1. In the breast epithelium, DEAR1 expression is limited to the ductal and glandular epithelium and is down-regulated in transition to ductal carcinoma in situ (DCIS), an early histologic stage in breast tumorigenesis. DEAR1 missense mutations and homozygous deletion (HD) were discovered in breast cancer cell lines and tumor samples. Introduction of the DEAR1 wild type and not the missense mutant alleles to complement a mutation in a breast cancer cell line, derived from a 36-year-old female with invasive breast cancer, initiated acinar morphogenesis in three-dimensional (3D) basement membrane culture and restored tissue architecture reminiscent of normal acinar structures in the mammary gland in vivo. Stable knockdown of DEAR1 in immortalized human mammary epithelial cells (HMECs) recapitulated the growth in 3D culture of breast cancer cell lines containing mutated DEAR1, in that shDEAR1 clones demonstrated disruption of tissue architecture, loss of apical basal polarity, diffuse apoptosis, and failure of lumen formation. Furthermore, immunohistochemical staining of a tissue microarray from a cohort of 123 young female breast cancer patients with a 20-year follow-up indicated that in early-onset breast cancer, DEAR1 expression serves as an independent predictor of local recurrence-free survival and correlates significantly with strong family history of breast cancer and the triple-negative phenotype (ER(-), PR(-), HER-2(-)) of breast cancers with poor prognosis. Conclusions: Our data provide compelling evidence for the genetic alteration and loss of expression of DEAR1 in breast cancer, for the functional role of DEAR1 in the dominant regulation of acinar morphogenesis in 3D culture, and for the potential utility of an immunohistochemical assay for DEAR1 expression as an independent prognostic marker for stratification of early-onset disease. C1 [Lott, Steven T.; Chen, Nanyue; Chandler, Dawn S.; Wang, Luo; Rodriguez, Marivonne; Xie, Hongyan; Balasenthil, Seetharaman; Chaung, Katrina; Zhang, Baili; Olufemi, Shodimu-Emmanu; Adams, Henry; Krahe, Ralf; Killary, Ann McNeill] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. [Yang, Qifeng; Haffty, Bruce] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, New Brunswick, NJ USA. [Buchholz, Thomas A.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Sahin, Aysegul A.; El-Naggar, Adel K.; Sen, Subrata] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. [Chen, Jinyun; Frazier, Marsha L.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Band, Vimla] Univ Nebraska Med Ctr, Dept Genet Cell Biol & Anat, Eppley Canc Ctr, Omaha, NE USA. [Keyomarsi, Khandan] Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA. [Hunt, Kelly K.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Lott, ST (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA. EM akillary@mdanderson.org OI Hewitt, Stephen/0000-0001-8283-1788 FU Texas Advanced Research Program; US Department of Defense; US National Cancer Institute Early Detection Research Network; US National Cancer Institution [T32 CA09299]; US National Kidney Foundation; Ladies Auxiliary to the Veterans of Foreign Wars; US National Cancer Institute [NCI CA-16672] FX The research described herein was supported by grants from the Texas Advanced Research Program, the US Department of Defense, and the US National Cancer Institute Early Detection Research Network to AMK. STL and DSC were supported by the US National Cancer Institution training grant (T32 CA09299), STL by the US National Kidney Foundation, and DSC by the Ladies Auxiliary to the Veterans of Foreign Wars. The M. D. Anderson core facilities for DNA sequencing, peptide synthesis, nucleic acid extraction, and histopathology are supported by a grant from the US National Cancer Institute (NCI CA-16672). Funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 22 Z9 22 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAY PY 2009 VL 6 IS 5 AR e1000068 DI 10.1371/journal.pmed.1000068 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 459ER UT WOS:000267084100014 PM 19536326 ER PT J AU Sarzotti-Kelsoe, M Cox, J Cleland, N Denny, T Hural, J Needham, L Ozaki, D Rodriguez-Chavez, IR Stevens, G Stiles, T Tarragona-Fiol, T Simkins, A AF Sarzotti-Kelsoe, Marcella Cox, Josephine Cleland, Naana Denny, Thomas Hural, John Needham, Leila Ozaki, Daniel Rodriguez-Chavez, Isaac R. Stevens, Gwynneth Stiles, Timothy Tarragona-Fiol, Tony Simkins, Anita TI Evaluation and Recommendations on Good Clinical Laboratory Practice Guidelines for Phase I-III Clinical Trials SO PLOS MEDICINE LA English DT Review ID PROFICIENCY; ELISPOT; HARMONIZATION; VALIDATION; IMMUNITY; ASSAY; CELL C1 [Sarzotti-Kelsoe, Marcella; Needham, Leila; Ozaki, Daniel] Duke Univ, Ctr AIDS Res, Cent QA Unit, Durham, NC 27710 USA. [Cox, Josephine] Int AIDS Vaccine Initiat, Rockville, MD USA. [Cleland, Naana] NIAID, Henry M Jackson Fdn Adv Mil Med, Div Aids, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Denny, Thomas; Needham, Leila] Ctr HIV AIDS Vaccine Immunol, Duke Human Vaccine Inst, Durham, NC USA. [Hural, John] HIV Vaccine Trials Network, Seattle, WA USA. [Stevens, Gwynneth] Int AIDS Vaccine Initiat, Johannesburg, Gauteng, South Africa. [Tarragona-Fiol, Tony] Univ London Imperial Coll Sci Technol & Med, Int AIDS Vaccine Initiat, Core Lab, London, England. [Simkins, Anita] AlphaVax Human Vaccines, Res Triangle Pk, NC USA. RP Sarzotti-Kelsoe, M (reprint author), Duke Univ, Ctr AIDS Res, Cent QA Unit, Durham, NC 27710 USA. EM msarzott@duke.edu OI Needham, Leila/0000-0003-3450-5042; Denny, Thomas/0000-0002-7364-8276 FU NIAID NIH HHS [HHSN272200800014C]; PHS HHS [HHSN272200800014C] NR 24 TC 28 Z9 28 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD MAY PY 2009 VL 6 IS 5 AR e1000067 DI 10.1371/journal.pmed.1000067 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 459ER UT WOS:000267084100009 PM 19536325 ER PT J AU Burbelo, PD Leahy, HP Iadarola, MJ Nutman, TB AF Burbelo, Peter D. Leahy, Hannah P. Iadarola, Michael J. Nutman, Thomas B. TI A Four-Antigen Mixture for Rapid Assessment of Onchocerca volvulus Infection SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; ANTIBODY CARD TEST; LOA-LOA INFECTION; RECOMBINANT ANTIGENS; FILARIAL NEMATODES; MOLECULAR-CLONING; ROC CURVE; DIAGNOSIS; PROTEINS; COCKTAIL AB Background: Onchocerciasis, an infection caused by the filarial nematode Onchocerca volvulus, is a major public health concern. Given the debilitating symptoms associated with onchocerciasis and concerns about recrudescence in areas of previous onchocerciasis control, more efficient tools are needed for diagnosis and monitoring of control measures. We investigated whether luciferase immunoprecipitation systems (LIPS) may be used as a more rapid, specific, and standardized diagnostic assay for Onchocerca volvulus infection. Methods: Four recombinantly produced Onchocerca volvulus antigens (Ov-FAR-1, Ov-API-1, Ov-MSA-1 and Ov-CPI-1) were tested by LIPS on a large cohort of blinded sera comprised of both uninfected controls and patients with a proven parasitic infection including Onchocerca volvulus (Ov), Wuchereria bancrofti (Wb), Loa loa (Ll), Strongyloides stercoralis (Ss), and with other potentially cross-reactive infections. In addition to testing all four Ov antigens separately, a mixture that tested all four antigens simultaneously was evaluated in the standard 2-hour incubation format as well as in a 15-minute rapid LIPS format. Findings: Antibody responses to the four different Ov antigens allowed for unequivocal differentiation between Ov-infected and uninfected control sera with 100% sensitivity and 100% specificity. Analysis of the antibody titers to each of these four antigens in individual Ov-infected sera revealed that they were markedly different and did not correlate (r(S) = -0.11 to 0.58; P = 0.001 to 0.89) to each other. Compared to Ov-infected sera, patients infected with Wb, Ll, Ss, and other conditions had markedly lower geometric mean antibody titers to each of the Ov 4 antigens (P<0.0002 for each antigen). The simplified method of using a mixture of the 4 Ov antigens simultaneously in the standard format or a quick 15-minute format (QLIPS) showed 100% sensitivity and 100% specificity in distinguishing the Ov-infected sera from the uninfected control sera. Finally, the QLIPS format had the best performance with 100% sensitivity and specificity values of 76%, 84% and 93% for distinguishing Ov from Wb, Ll and Ss-infected sera. Conclusions: The multi-antigen LIPS assay can be used as a rapid, high throughput, and specific tool to not only to diagnose individual Ov infections but also as a sensitive and potentially point-of-care method for early detection of recrudescent infections in areas under control and for mapping new areas of transmission of Ov infection. C1 [Burbelo, Peter D.; Leahy, Hannah P.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA. [Nutman, Thomas B.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD USA. EM tnutman@niaid.nih.gov FU National Institute of Dental and Craniofacial Research; National Institute of Allergy and Infectious Diseases FX This study was supported by the intramural research programs (DIR) of the National Institute of Dental and Craniofacial Research and the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 43 Z9 43 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2009 VL 3 IS 5 AR e438 DI 10.1371/journal.pntd.0000438 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 461LH UT WOS:000267268000011 PM 19436728 ER PT J AU Mondini, A Bronzoni, RVD Nunes, SHP Neto, FC Massad, E Alonso, WJ Lazzaro, ESM Ferraz, AA Zanotto, PMD Nogueira, ML AF Mondini, Adriano de Moraes Bronzoni, Roberta Vieira Pereira Nunes, Silvia Helena Chiaravalloti Neto, Francisco Massad, Eduardo Alonso, Wladimir J. Lazzaro, Eduardo S. M. Ferraz, Amena Alcantara de Andrade Zanotto, Paolo Marinho Nogueira, Mauricio Lacerda TI Spatio-Temporal Tracking and Phylodynamics of an Urban Dengue 3 Outbreak in Sao Paulo, Brazil SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID AEDES-AEGYPTI; MOLECULAR EPIDEMIOLOGY; VIRUS CIRCULATION; YELLOW-FEVER; TRANSMISSION; EVOLUTION; DISPERSAL; FLAVIVIRUSES; POPULATION; THAILAND AB The dengue virus has a single-stranded positive-sense RNA genome of similar to 10.700 nucleotides with a single open reading frame that encodes three structural (C, prM, and E) and seven nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins. It possesses four antigenically distinct serotypes (DENV 1-4). Many phylogenetic studies address particularities of the different serotypes using convenience samples that are not conducive to a spatio-temporal analysis in a single urban setting. We describe the pattern of spread of distinct lineages of DENV-3 circulating in Sao Jose do Rio Preto, Brazil, during 2006. Blood samples from patients presenting dengue-like symptoms were collected for DENV testing. We performed M-N-PCR using primers based on NS5 for virus detection and identification. The fragments were purified from PCR mixtures and sequenced. The positive dengue cases were geo-coded. To type the sequenced samples, 52 reference sequences were aligned. The dataset generated was used for iterative phylogenetic reconstruction with the maximum likelihood criterion. The best demographic model, the rate of growth, rate of evolutionary change, and Time to Most Recent Common Ancestor (TMRCA) were estimated. The basic reproductive rate during the epidemics was estimated. We obtained sequences from 82 patients among 174 blood samples. We were able to geo-code 46 sequences. The alignment generated a 399-nucleotide-long dataset with 134 taxa. The phylogenetic analysis indicated that all samples were of DENV-3 and related to strains circulating on the isle of Martinique in 2000-2001. Sixty DENV-3 from Sao Jose do Rio Preto formed a monophyletic group (lineage 1), closely related to the remaining 22 isolates (lineage 2). We assumed that these lineages appeared before 2006 in different occasions. By transforming the inferred exponential growth rates into the basic reproductive rate, we obtained values for lineage 1 of R(0) = 1.53 and values for lineage 2 of R(0) = 1.13. Under the exponential model, TMRCA of lineage 1 dated 1 year and lineage 2 dated 3.4 years before the last sampling. The possibility of inferring the spatio-temporal dynamics from genetic data has been generally little explored, and it may shed light on DENV circulation. The use of both geographic and temporally structured phylogenetic data provided a detailed view on the spread of at least two dengue viral strains in a populated urban area. C1 [Mondini, Adriano; de Moraes Bronzoni, Roberta Vieira; Pereira Nunes, Silvia Helena; Chiaravalloti Neto, Francisco; Nogueira, Mauricio Lacerda] Fac Med Sao Jose do Rio Preto, Sao Jose Do Rio Preto, Brazil. [Chiaravalloti Neto, Francisco] Superintendencia Controle Endemias, Sao Jose Do Rio Preto, Brazil. [Massad, Eduardo] Univ Sao Paulo, Fac Med, LIM HCFMUSP 01, Sao Paulo, Brazil. [Alonso, Wladimir J.] NIH, Forgarty Int Ctr, Bethesda, MD 20892 USA. [Lazzaro, Eduardo S. M.; Ferraz, Amena Alcantara] Secretaria Municipal Saude & Higiene Sao Jose do, Sao Jose Do Rio Preto, Brazil. [de Andrade Zanotto, Paolo Marinho] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, LEMB, BR-05508 Sao Paulo, Brazil. RP Mondini, A (reprint author), Fac Med Sao Jose do Rio Preto, Sao Jose Do Rio Preto, Brazil. EM mauricio.nogueira@pq.cnpq.br RI Massad, Eduardo/H-6143-2011; Nogueira, Mauricio/B-7599-2012; Bronzoni, Roberta/J-8917-2012; Massad, Eduardo/B-1169-2012; Mondini, Adriano/F-7446-2012; Chiaravalloti Neto, F*/F-8006-2012 OI Nogueira, Mauricio/0000-0003-1102-2419; Massad, Eduardo/0000-0002-7200-2916; Mondini, Adriano/0000-0002-5557-9721; FU FAPESP [04/11098-2, 06/01070-9]; FINEP; CAPES FX This work was supported by FAPESP grants to MLN (04/11098-2) and FCN (06/01070-9). MLN is supported by a FINEP grant (Genprot DENGUE). RVMB is a recipient of a FAPESP fellowship. AM is a recipient of a CAPES scholarship. This work is s supported in part by the Viral Genetic Diversity Network (FAPESP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 27 Z9 28 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2009 VL 3 IS 5 AR e448 DI 10.1371/journal.pntd.0000448 PG 15 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 461LH UT WOS:000267268000017 PM 19478848 ER PT J AU Collin, N Gomes, R Teixeira, C Cheng, L Laughinghouse, A Ward, JM Elnaiem, DE Fischer, L Valenzuela, JG Kamhawi, S AF Collin, Nicolas Gomes, Regis Teixeira, Clarissa Cheng, Lily Laughinghouse, Andre Ward, Jerrold M. Elnaiem, Dia-Eldin Fischer, Laurent Valenzuela, Jesus G. Kamhawi, Shaden TI Sand Fly Salivary Proteins Induce Strong Cellular Immunity in a Natural Reservoir of Visceral Leishmaniasis with Adverse Consequences for Leishmania SO PLOS PATHOGENS LA English DT Article ID LUTZOMYIA-LONGIPALPIS; CUTANEOUS LEISHMANIASIS; LEISHMUNE(R) VACCINE; VECTOR; PROTECTION; DOGS; IDENTIFICATION; ANTIGENS; CHAGASI; BRAZIL AB Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2) antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response. C1 [Collin, Nicolas; Gomes, Regis; Teixeira, Clarissa; Elnaiem, Dia-Eldin; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Cheng, Lily; Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Laughinghouse, Andre] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Fischer, Laurent] Lab Lyon Gerland, Merial SAS, R&D, Lyon, France. RP Collin, N (reprint author), NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jvalenzuela@niaid.nih.gov; skamhawi@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases at the National Institutes of Health; Merial Limited FX This work was supported through the intramural program of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, and by Merial Limited. Merial Limited had a role in the design of immunization regimens but no role in data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 59 Z9 61 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2009 VL 5 IS 5 AR e1000441 DI 10.1371/journal.ppat.1000441 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 459FH UT WOS:000267085800023 PM 19461875 ER PT J AU Dey, B Svehla, K Xu, L Wycuff, D Zhou, TQ Voss, G Phogat, A Chakrabarti, BK Li, YX Shaw, G Kwong, PD Nabel, GJ Mascola, JR Wyatt, RT AF Dey, Barna Svehla, Krisha Xu, Ling Wycuff, Dianne Zhou, Tongqing Voss, Gerald Phogat, Adhuna Chakrabarti, Bimal K. Li, Yuxing Shaw, George Kwong, Peter D. Nabel, Gary J. Mascola, John R. Wyatt, Richard T. TI Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site SO PLOS PATHOGENS LA English DT Article ID B-CELL RESPONSES; ENVELOPE GLYCOPROTEIN; PEPTIDE EPITOPE; NEUTRALIZING ANTIBODIES; CONFORMATIONAL-CHANGES; MACAQUE MONKEYS; CD4-BOUND STATE; CHIMERIC VIRUS; IMMUNODEFICIENCY; IMMUNOGENICITY AB The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region. C1 [Dey, Barna; Svehla, Krisha; Xu, Ling; Wycuff, Dianne; Zhou, Tongqing; Phogat, Adhuna; Chakrabarti, Bimal K.; Li, Yuxing; Kwong, Peter D.; Nabel, Gary J.; Mascola, John R.; Wyatt, Richard T.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Voss, Gerald] GlaxoSmithKline Biol, Rixensart, Belgium. [Shaw, George] Univ Alabama, Birmingham, AL USA. RP Dey, B (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU National Institute of Allergy and Infectious Diseases intramural program; International AIDS Vaccine Initiative (IAVI); Bill and Melinda Gates Foundation FX This study was supported by the National Institute of Allergy and Infectious Diseases intramural program and funding from the International AIDS Vaccine Initiative (IAVI) and the Bill and Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 84 Z9 85 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2009 VL 5 IS 5 AR e1000445 DI 10.1371/journal.ppat.1000445 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 459FH UT WOS:000267085800004 PM 19478876 ER PT J AU Moayeri, M Crown, D Dorward, DW Gardner, D Ward, JM Li, Y Cui, XZ Eichacker, P Leppla, SH AF Moayeri, Mahtab Crown, Devorah Dorward, David W. Gardner, Don Ward, Jerrold M. Li, Yan Cui, Xizhong Eichacker, Peter Leppla, Stephen H. TI The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS) SO PLOS PATHOGENS LA English DT Article ID TRANSLATIONAL SAFETY BIOMARKER; DIRECTED MONOCLONAL-ANTIBODY; ACID-BINDING PROTEIN; BACILLUS-ANTHRACIS; MYOCARDIAL-INFARCTION; XANTHINE OXIDOREDUCTASE; CARDIAC TROPONIN; ENDOTHELIAL-CELLS; REGULATES BASAL; KNOCKOUT MICE AB Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS-/- mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectural changes in heart morphology of nNOS-/- mice, with rapid appearance of novel inter-fiber spaces but no associated apoptosis of cardiomyocytes. LT-treated WT mice had no histopathology observed at the light microscopy level. Electron microscopic analyses of LT-treated mice, however, revealed striking pathological changes in the hearts of both nNOS-/- and WT mice, varying only in severity and timing. Endothelial/capillary necrosis and degeneration, inter-myocyte edema, myofilament and mitochondrial degeneration, and altered sarcoplasmic reticulum cisternae were observed in both LT-treated WT and nNOS-/- mice. Furthermore, multiple biomarkers of cardiac injury (myoglobin, cardiac troponin-I, and heart fatty acid binding protein) were elevated in LT-treated mice very rapidly (by 6 h after LT injection) and reached concentrations rarely reported in mice. Cardiac protective nitrite therapy and allopurinol therapy did not have beneficial effects in LT-treated mice. Surprisingly, the potent nitric oxide scavenger, carboxy-PTIO, showed some protective effect against LT. Echocardiography on LT-treated mice indicated an average reduction in ejection fraction following LT treatment in both nNOS-/- and WT mice, indicative of decreased contractile function in the heart. We report the heart as an early target of LT in mice and discuss a protective role for nNOS against LT-mediated cardiac damage. C1 [Moayeri, Mahtab; Crown, Devorah; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. [Dorward, David W.; Gardner, Don] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Ward, Jerrold M.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Li, Yan; Cui, Xizhong; Eichacker, Peter] Natl Inst Hlth Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD USA. RP Moayeri, M (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural Research Program of the NIH; National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 80 TC 28 Z9 29 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2009 VL 5 IS 5 AR e1000456 DI 10.1371/journal.ppat.1000456 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 459FH UT WOS:000267085800013 PM 19478875 ER PT J AU Scull, MA Gillim-Ross, L Santos, C Roberts, KL Bordonali, E Subbarao, K Barclay, WS Pickles, RJ AF Scull, Margaret A. Gillim-Ross, Laura Santos, Celia Roberts, Kim L. Bordonali, Elena Subbarao, Kanta Barclay, Wendy S. Pickles, Raymond J. TI Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways SO PLOS PATHOGENS LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; RECEPTOR SPECIFICITY; A VIRUS; CILIATED CELLS; HOST-RANGE; IN-VITRO; INFECTION; H5N1; HEMAGGLUTININ; NEURAMINIDASE AB Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37 degrees C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal airways (32 degrees C). These data support the hypothesis that avian influenza viruses, ordinarily adapted to the temperature of the avian enteric tract (40 degrees C), rarely infect humans, in part due to differences in host airway regional temperatures. Previously, a critical residue at position 627 in the avian influenza virus polymerase subunit, PB2, was identified as conferring temperature-dependency in mammalian cells. Here, we use reverse genetics to show that avianization of residue 627 attenuates a human virus, but does not account for the different infection between 32 degrees C and 37 degrees C. To determine the mechanism of temperature restriction of avian influenza viruses in HAE at 32 degrees C, we generated recombinant human influenza viruses in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background that contained avian or avian-like glycoproteins. Two of these viruses, A/Victoria/3/75 with L226Q and S228G mutations in hemagglutinin (HA) and neuraminidase (NA) from A/Chick/Italy/1347/99 and A/PR/8/34 containing the H7 and N1 from A/Chick/Italy/1347/99, exhibited temperature restriction approaching that of wholly avian influenza viruses. These data suggest that influenza viruses bearing avian or avian-like surface glycoproteins have a reduced capacity to establish productive infection at the temperature of the human proximal airways. This temperature restriction may limit zoonotic transmission of avian influenza viruses and suggests that adaptation of avian influenza viruses to efficient infection at 32 degrees C may represent a critical evolutionary step enabling human-to-human transmission. C1 [Scull, Margaret A.; Pickles, Raymond J.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27515 USA. [Scull, Margaret A.; Pickles, Raymond J.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Gillim-Ross, Laura; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, Resp Viruses Sect, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Roberts, Kim L.; Barclay, Wendy S.] Univ London Imperial Coll Sci Technol & Med, Dept Virol, Div Investigat Sci, Fac Med, London, England. [Bordonali, Elena] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Scull, MA (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27515 USA. EM branston@med.unc.edu FU National Institutes of Health (NIH) [5-T32-AI007419, NIH R01 HL77844-1, NIH R21 HL080098-01, SCCOR 5 P50 HL084934, MRC G0600504]; Triangle Community Foundation; Wellcome Trust FX This work was supported by the National Institutes of Health (NIH) Molecular Biology of Viral Diseases Training Grant 5-T32-AI007419, NIH R01 HL77844-1, NIH R21 HL080098-01, SCCOR 5 P50 HL084934, and MRC G0600504. MAS (nee Hennessey) is a recipient of the George H. Hitchings Fund for Health Research and Science Education of the Triangle Community Foundation. WSB is a member of the Wellcome Trust-funded Centre for Respiratory Infection Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 41 Z9 41 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2009 VL 5 IS 5 AR e1000424 DI 10.1371/journal.ppat.1000424 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 459FH UT WOS:000267085800029 PM 19436701 ER PT J AU Tewalt, EF Grant, JM Granger, EL Palmer, DC Heuss, ND Gregerson, DS Restifo, NP Norbury, CC AF Tewalt, Eric F. Grant, Jean M. Granger, Erica L. Palmer, Douglas C. Heuss, Neal D. Gregerson, Dale S. Restifo, Nicholas P. Norbury, Christopher C. TI Viral Sequestration of Antigen Subverts Cross Presentation to CD8(+) T Cells SO PLOS PATHOGENS LA English DT Article ID CLASS-I MOLECULES; RECOMBINANT VACCINIA VIRUS; EXOGENOUS SOLUBLE-ANTIGEN; DENDRITIC CELLS; TRANSGENIC MICE; BETA-GALACTOSIDASE; SMALLPOX VACCINES; EXPRESSION; VIVO; RESPONSES AB Virus-specific CD8(+) T cells (TCD8+) are initially triggered by peptide-MHC Class I complexes on the surface of professional antigen presenting cells (pAPC). Peptide-MHC complexes are produced by two spatially distinct pathways during virus infection. Endogenous antigens synthesized within virus-infected pAPC are presented via the direct-presentation pathway. Many viruses have developed strategies to subvert direct presentation. When direct presentation is blocked, the cross-presentation pathway, in which antigen is transferred from virus-infected cells to uninfected pAPC, is thought to compensate and allow the generation of effector TCD8+. Direct presentation of vaccinia virus (VACV) antigens driven by late promoters does not occur, as an abortive infection of pAPC prevents production of these late antigens. This lack of direct presentation results in a greatly diminished or ablated TCD8+ response to late antigens. We demonstrate that late poxvirus antigens do not enter the cross-presentation pathway, even when identical antigens driven by early promoters access this pathway efficiently. The mechanism mediating this novel means of viral modulation of antigen presentation involves the sequestration of late antigens within virus factories. Early antigens and cellular antigens are cross-presented from virus-infected cells, as are late antigens that are targeted to compartments outside of the virus factories. This virus-mediated blockade specifically targets the cross-presentation pathway, since late antigen that is not cross-presented efficiently enters the MHC Class II presentation pathway. These data are the first to describe an evasion mechanism employed by pathogens to prevent entry into the cross-presentation pathway. In the absence of direct presentation, this evasion mechanism leads to a complete ablation of the TCD8+ response and a potential replicative advantage for the virus. Such mechanisms of viral modulation of antigen presentation must also be taken into account during the rational design of antiviral vaccines. C1 [Tewalt, Eric F.; Grant, Jean M.; Granger, Erica L.; Norbury, Christopher C.] Penn State Univ, Milton S Hershey Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. [Palmer, Douglas C.; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Palmer, Douglas C.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Heuss, Neal D.; Gregerson, Dale S.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. RP Tewalt, EF (reprint author), Penn State Univ, Milton S Hershey Coll Med, Dept Microbiol & Immunol, Hershey, PA USA. EM ccn1@psu.edu RI Restifo, Nicholas/A-5713-2008; Palmer, Douglas/B-9454-2008; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU National Institutes of Health [RO1A AI056094, AI070537]; PA-DOH Commonwealth Tobacco Settlement Fund [T32 CA60395, C06 RR-15428] FX Work was supported by National Institutes of Health grants RO1A AI056094 and AI070537, PA-DOH Commonwealth Tobacco Settlement Fund grant to CCN, T32 CA60395 (P.I.R Courtney) and C06 RR-15428 to the Penn State College of Medicine Department of Comparative Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript NR 49 TC 15 Z9 15 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD MAY PY 2009 VL 5 IS 5 AR e1000457 DI 10.1371/journal.ppat.1000457 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 459FH UT WOS:000267085800014 PM 19478869 ER PT J AU Savitz, J Lucki, I Drevets, WC AF Savitz, Jonathan Lucki, Irwin Drevets, Wayne C. TI 5-HT1A receptor function in major depressive disorder SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Major depressive disorder; 5-HT1A; HTR1A; PET; MRI; Genetics ID POSITRON-EMISSION-TOMOGRAPHY; SEROTONIN 1A RECEPTOR; DORSAL RAPHE NUCLEUS; MESSENGER-RNA EXPRESSION; LONG-TERM POTENTIATION; PROTEIN-KINASE-A; REPEATED ELECTROCONVULSIVE SHOCK; ANTIDEPRESSANT DRUG-ACTION; ADENYLYL-CYCLASE ACTIVITY; PLACEBO-CONTROLLED TRIAL AB Dysfunction of the serotonin 1A receptor (5-HT1A) may play a role in the genesis of major depressive disorder (MDD). Here we review the pharmacological, post-mortem, positron emission tomography (PET), and genetic evidence in support of this statement. We also touch briefly on two MIDD-associated phenotypes, cognitive impairment and somatic pain. The results of pharmacological challenge studies with 5-HT1A receptor agonists are indicative of blunted endocrine responses in depressed patients. Lithium, valproate, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other treatment, such as electroconvulsive shock therapy (ECT), all increase post-synaptic 5-HT1A receptor signaling through either direct or indirect effects. Reduced somatodendritic and postsynaptic 5-HT1A receptor numbers or affinity have been reported in some post-mortem studies of suicide victims, a result consistent with well-replicated PET analyses demonstrating reduced 5-HT1A receptor binding potential in diverse regions such as the dorsal raphe, medial prefrontal cortex (mPFC), amygdala and hippocampus. 5-HT1A receptor knockout (KO) mice display increased anxiety-related behavior, which, unlike in their wild-type counterparts, cannot be rescued with antidepressant drug (AD) treatment. In humans, the G allele of a single nucleotide polymorphism (SNP) in the 5-HT1A receptor gene (HTR1A; rs6295), which abrogates a transcription factor binding site for deformed epidermal autoregulatory factor-1 (Deaf-1) and Hes5, has been reported to be over-represented in MDD cases. Conversely, the C allele has been associated with better response to AD drugs. We raise the possibility that 5-HT1A receptor dysfunction represents one potential mechanism underpinning MDD and other stress-related disorders. Published by Elsevier Ltd. C1 [Savitz, Jonathan; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Lucki, Irwin] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Savitz, J (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. EM savitzj@mail.nih.gov RI Savitz, Jonathan/C-3088-2009 OI Savitz, Jonathan/0000-0001-8143-182X FU Intramural NIH HHS [Z99 MH999999] NR 284 TC 271 Z9 288 U1 4 U2 44 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD MAY PY 2009 VL 88 IS 1 BP 17 EP 31 DI 10.1016/j.pneurobio.2009.01.009 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 450KJ UT WOS:000266399100002 PM 19428959 ER PT J AU Singh, RP Brooks, BR Klauda, JB AF Singh, Rishi P. Brooks, Bernard R. Klauda, Jeffery B. TI Binding and release of cholesterol in the Osh4 protein of yeast SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE molecular simulation; molecular dynamics; oxysterol binding proteins; sterol transport; protein function; steered molecular dynamics ID STEERED MOLECULAR-DYNAMICS; NONVESICULAR STEROL TRANSPORT; OSBP-RELATED PROTEINS; LACTOSE PERMEASE; FORCE-FIELDS; SIMULATIONS; FAMILY; COMPLEX AB Sterols have been shown experimentally to bind to the Osh4 protein (a homolog of the oxysterol binding proteins) of Saccharomyces cerevisiae within a binding tunnel, which consists of antiparallel beta-sheets that resemble a beta-barrel and three a-helices of the N-terminus. This and other Osh proteins are essential for intracellular transport of sterols and ultimately cell life. Molecular dynamics (MD) simulations are used to study the binding of cholesterol to Osh4 at the atomic level. The structure of the protein is stable during the course of all MD simulations and has little deviation from the experimental crystal structure. The conformational stability of cholesterol within the binding tunnel is aided in part by direct or water-mediated interactions between the 3-hydroxyl (3-OH) group of cholesterol and Trp(46), Gln(96), Tyr(97), Asn(165), and/or Gln(181) as well as dispersive interactions with Phe(42), Leu(24), Leu(39), Ile(167), and Ile(203). These residues along with other nonpolar residues in the binding tunnel and lid contribute nearly 75% to the total binding energy. The strongest and most populated interaction is between Gin 96 and 3-OH with a cholesterol/Gln(96) interaction energy of -4.5 +/- 1.0 kcal/mol. Phe(42) has a similar level of attraction to cholesterol with -4.1 +/- 0.3 kcal/mol. A MD simulation without the N-terminus lid that covers the binding tunnel resulted in similar binding conformations and binding energies when compared with simulations with the full-length protein. Steered MD was used to determine details of the mechanism used by Osh4 to release cholesterol to the cytoplasm. Phe(42), Gln(96), Asn(165), Gln(181), Pro(211), and Ile(206) are found to direct the cholesterol as it exits the binding tunnel as well as Lys(109). The mechanism of sterol release is conceptualized as a molecular ladder with the rungs being amino acids or water-mediated amino acids that interact with 3-OH. C1 [Klauda, Jeffery B.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Singh, Rishi P.; Brooks, Bernard R.; Klauda, Jeffery B.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Klauda, JB (reprint author), Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. EM jbklauda@umd.edu FU Intramural NIH HHS [Z01 HL001050-10, Z01 HL001027-25] NR 31 TC 16 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD MAY 1 PY 2009 VL 75 IS 2 BP 468 EP 477 DI 10.1002/prot.22263 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 418SP UT WOS:000264169400018 PM 18937371 ER PT J AU Li, X Hoffman, AF Peng, XQ Lupica, CR Gardner, EL Xi, ZX AF Li, Xia Hoffman, Alexander F. Peng, Xiao-Qing Lupica, Carl R. Gardner, Eliot L. Xi, Zheng-Xiong TI Attenuation of basal and cocaine-enhanced locomotion and nucleus accumbens dopamine in cannabinoid CB1-receptor-knockout mice SO PSYCHOPHARMACOLOGY LA English DT Article DE Cannabinoid; CB1 receptor; Cocaine; Dopamine; Locomotion; Nucleus accumbens ID RECEPTOR KNOCKOUT MICE; VENTRAL TEGMENTAL AREA; INDUCED BEHAVIORAL SENSITIZATION; CONDITIONED PLACE PREFERENCE; AGONIST WIN 55,212-2; FREELY-MOVING RATS; DRUG-ADDICTION; CB1 RECEPTORS; ENDOGENOUS CANNABINOIDS; GLUTAMATERGIC SYNAPSES AB Effect of cannabinoid CB1 receptor deletion on cocaine's actions is controversial. This is partly based on findings in CB1-receptor-knockout (CB1(-/-)) mice with CD1 genetic background. In the present study, we used CB1(-/-) mice with a C57BL/6J genetic background to further investigate the role of CB1 receptors in cocaine's action. Locomotor activity was assessed using AccuScan locomotor chambers. Brain extracellular dopamine (DA) levels were measured by in vivo microdialysis and by fast-scan cyclic voltammetry in the nucleus accumbens (NAc). CB1(-/-) mice displayed a significant reduction in basal levels of locomotion and extracellular DA, as well as in cocaine-enhanced locomotion and extracellular DA, as compared to their wild-type (CB1(+/+)) littermates. The reduction in basal and cocaine-enhanced DA appears to be related to a reduction in basal DA release, not to an increase in DA clearance, as indicated by fast-scan cyclic voltammetry in brain slices. Pharmacological blockade of CB1 receptors by SR141716 inhibited locomotion and NAc DA release in CB1(+/+) mice. The present findings suggest an important role for CB1 receptors in mediating cocaine's behavioral and neurochemical effects. C1 [Li, Xia; Peng, Xiao-Qing; Gardner, Eliot L.; Xi, Zheng-Xiong] Natl Inst Drug Abuse, Neuropsychopharmacol Sect, Chem Biol Res Branch, Baltimore, MD 21224 USA. [Hoffman, Alexander F.; Lupica, Carl R.] Natl Inst Drug Abuse, Neurophysiol Sect, Cellular Neurobiol Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Neuropsychopharmacol Sect, Chem Biol Res Branch, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov RI Hoffman, Alexander/H-3035-2012; OI Hoffman, Alexander/0000-0002-2676-0628; PENG, XIAOQING/0000-0002-7272-5428 FU National Institute on Drug Abuse, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 62 TC 31 Z9 31 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2009 VL 204 IS 1 BP 1 EP 11 DI 10.1007/s00213-008-1432-0 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 436AT UT WOS:000265385700001 PM 19099297 ER PT J AU Kitanaka, J Kitanaka, N Tatsuta, T Hall, FS Uhl, GR Tanaka, K Nishiyama, N Morita, Y Takemura, M AF Kitanaka, J. Kitanaka, N. Tatsuta, T. Hall, F. S. Uhl, G. R. Tanaka, K. Nishiyama, N. Morita, Y. Takemura, M. TI Sigma(1) receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE Methamphetamine; Stereotypy; Sniffing; Biting; BMY 14802; Sigma ligand; Sigma receptor ID SELF-INJURIOUS-BEHAVIOR; DOPAMINE RELEASE; AMPHETAMINE MICROINJECTION; LOCOMOTOR-ACTIVITY; INDUCED AROUSAL; 6-OHDA LESIONS; ANIMAL-MODELS; IN-VIVO; COCAINE; RAT AB The effects of sigma receptor antagonists on methamphetamine (METH)-induced stereotypy have not been examined. We examined the effects of sigma antagonists on METH-induced stereotypy in mice. The administration of METH (10 mg/kg) to male ddY mice induced stereotyped behavior consisting of biting (90.1%), sniffing (4.2%), head bobbing (4.1%), and circling (1.7%) during an observation period of 1 h. Pretreatment of the mice with BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol; 1, 5, and 10 mg/kg), a non-specific sigma receptor antagonist, significantly increased METH-induced sniffing (19.2%, 30.5%, and 43.8% of total stereotypical behavior) but decreased biting (76.6%, 66.9%, and 49.3% of total stereotypical behavior) in a dose-dependent manner. This response was completely abolished by (+)-SKF 10,047 ([2S-(2 alpha,6 alpha,11R)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol; 4 and 10 mg/kg), a putative sigma(1) receptor agonist, and partially by PB 28 (1-cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalen-1-yl)-n-propyl]piperazine; 1 and 10 mg/kg), a putative sigma(2) receptor agonist. The BMY 14802 action on METH-induced stereotypy was mimicked by BD 1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine; 10 mg/kg), a putative sigma(1) receptor antagonist, but not by SM-21 ((+/-)-tropanyl 2-(4-chlorophenoxy)butanoate; 1 mg/kg), a putative sigma(2) receptor antagonist. The BD 1047 effect on METH-induced stereotypy was also abolished completely by (+)-SKF 10,047 and partially by PB 28. The overall frequency of METH-induced stereotypical behavior was unchanged with these sigma receptor ligands, despite the alteration in particular behavioral patterns. The BMY 14802 action on METH-induced stereotypy was unaffected by pretreatment with centrally acting histamine H-1 receptor antagonists (pyrilamine or ketotifen, 10 mg/kg), suggesting that these effects are independent of histamine H-1 receptor signaling systems. In summary, modulation of central sigma(1) receptors alters the pattern of METH-induced stereotypy, producing a shift from stereotypical biting to stereotypical sniffing, without affecting the overall frequency of stereotypical behavior. C1 [Kitanaka, J.; Kitanaka, N.; Takemura, M.] Hyogo Coll Med, Dept Pharmacol, Nishinomiya, Hyogo 6638501, Japan. [Tatsuta, T.; Morita, Y.] Hyogo Coll Med, Dept Neuropsychiat, Nishinomiya, Hyogo 6638501, Japan. [Hall, F. S.; Uhl, G. R.] Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, NIH,US Dept HHS, Baltimore, MD 21224 USA. [Tanaka, K.; Nishiyama, N.] Hyogo Univ Hlth Sci, Sch Pharm, Dept Pharm, Div Pharmacol,Chuo Ku, Kobe, Hyogo 6508530, Japan. RP Kitanaka, J (reprint author), Hyogo Coll Med, Dept Pharmacol, 1-1 Mukogawa Cho, Nishinomiya, Hyogo 6638501, Japan. EM kitanaka-hyg@umin.net RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU Hyogo College of Medicine; National Institute on Drug Abuse (NIH/DHHS, USA, GRU, FSH) FX The authors are grateful to Dr. Morio Yamada of the Department of Chemistry, Hyogo College of Medicine, for valuable comments on the manuscript. We also thank Dr. Tsung-Ping Su of the National Institute on Drug Abuse-IRP (USA) and Dr. Nicola A. Colabufo of Dipartimento Farmaco-Chimico, Universita di Bari, Italy, for their advice on the sigma receptor ligand properties. This research was supported, in part, by Grants-in-Aid for Researchers, Hyogo College of Medicine (2005 to NK, 2007 to JK) and intramural funding from the National Institute on Drug Abuse (NIH/DHHS, USA, GRU, FSH). NR 64 TC 14 Z9 14 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2009 VL 203 IS 4 BP 781 EP 792 DI 10.1007/s00213-008-1425-z PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 426HX UT WOS:000264699700014 PM 19052726 ER PT J AU Nuruddin, R Lim, MK Hadden, WC Azam, I AF Nuruddin, Rozina Lim, Meng Kin Hadden, Wilbur C. Azam, Iqbal TI Comparison of estimates of under-nutrition for pre-school rural Pakistani children based on the WHO standard and the National Center for Health Statistics (NCHS) reference SO PUBLIC HEALTH NUTRITION LA English DT Article DE NCHS growth reference; Pre-school children; Pakistan; Under-nutrition prevalence; WHO growth standard ID INTERNATIONAL GROWTH REFERENCE; YOUNG-CHILDREN; FED INFANTS; COUNTRIES; CHARTS; MALNUTRITION; ORGANIZATION; POPULATION AB Objective: To compare estimates of under-nutrition among pre-school Pakistani children using the WHO growth standard and the National Center for Health Statistics (NCHS) reference. Design: Prevalence of stunting, wasting and underweight as defined by WHO and NCHS standards are calculated and compared. Setting: The data are from two cross-sectional surverys conducted in the early 1990s, the time frame for setting the baseline for the Millennium Development Goals: (i) National Health Survey of Pakistan (NHSP) assessed the health status of a nationally representative sample and (ii) Thatta Health System Research Project (THSRP) was a survey in Thatta, a rural district of Sindh Province. Subejcts: In all, 1533 and 1051 children aged 0-35 months from national and Thatta surveys, respectively. Results: WHO standard gave a significantly higher prevalence of stunting for both national [36.7 (95% CI 33.2, 40.2)] and Thatta surveys [52.9 (95% CI 48.9, 56-9)] compared to the NCHS reference [national 29.1 (95% CI 25.9, 32.2) and Thatta: 44.8 (95% CI 41.1, 48.5), respectively]. It also gave significantly higher prevalence of wasting for the Thatta survey [22.9 (95% CI 20.3, 25.5)] compared to the NCHS reference [15.7 (95% CI 13.5, 17.8)]. Differences due to choice of standard were pronounced during infancy and for severely wasted and severely stunted children. Conclusions: Pakistan should switch to the robustly constructed and up-to-date WHO growth standard for assessing under-nutrition. New growth charts should be introduced along with training for health workers. This has implications for nutritional intervention programmes, for resetting the country's targets for Millennium Development Goal 1 and for monitoring nutritional trends. C1 [Nuruddin, Rozina; Azam, Iqbal] Aga Khan Univ, Dept Community Hlth Sci, Karachi 74800, Pakistan. [Nuruddin, Rozina] Natl Univ Singapore, Pakistan & Dept Community Occupat & Family Med, Singapore 117597, Singapore. [Lim, Meng Kin] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117597, Singapore. [Hadden, Wilbur C.] NIA, Bethesda, MD 20892 USA. RP Nuruddin, R (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Karachi 74800, Pakistan. EM rozina.nuruddin@aku.edu NR 38 TC 13 Z9 13 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1368-9800 J9 PUBLIC HEALTH NUTR JI Public Health Nutr. PD MAY PY 2009 VL 12 IS 5 BP 716 EP 722 DI 10.1017/S1368980008002383 PG 7 WC Public, Environmental & Occupational Health; Nutrition & Dietetics SC Public, Environmental & Occupational Health; Nutrition & Dietetics GA 440AL UT WOS:000265669900020 PM 18503722 ER PT J AU Berger, VW AF Berger, Vance W. TI Do not test for baseline imbalances unless they are known to be present? SO QUALITY OF LIFE RESEARCH LA English DT Editorial Material C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Berger, Vance W.] Univ Maryland Baltimore Cty, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 31316130,Execut Blvd,MSC 735, Bethesda, MD 20892 USA. EM vb78c@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 2 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 EI 1573-2649 J9 QUAL LIFE RES JI Qual. Life Res. PD MAY PY 2009 VL 18 IS 4 BP 399 EP 399 DI 10.1007/s11136-009-9452-8 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 428IZ UT WOS:000264842500001 PM 19241142 ER PT J AU Ferrell, G Lu, MY Stoddard, P Sammel, MD Romero, R Strauss, JF Matthews, CA AF Ferrell, Georgia Lu, Minyan Stoddard, Paul Sammel, Mary D. Romero, Roberto Strauss, Jerome F., III Matthews, Catherine A. TI A Single Nucleotide Polymorphism in the Promoter of the LOXL1 Gene and Its Relationship to Pelvic Organ Prolapse and Preterm Premature Rupture of Membranes SO REPRODUCTIVE SCIENCES LA English DT Article DE Lysyl oxidase-like 1; pelvic organ prolapse; preterm premature rupture of membranes; elastin ID HUMAN FETAL MEMBRANES; QUALITY-OF-LIFE; AFRICAN-AMERICANS; EXFOLIATION GLAUCOMA; UROGENITAL PROLAPSE; AMNIOTIC MEMBRANES; COLLAGEN CONTENT; RISK-FACTORS; WOMEN; SUSCEPTIBILITY AB Pelvic organ prolapse and preterm premature rupture of membranes, the 2 conditions which have in common weakening of the tensile strength of tissues, are thought to be caused, in part, by abnormal extracellular matrix synthesis and/or catabolism. We identified a new single nucleotide polymorphism (NT_010194(LOX1):g.45008784A>C) in the promoter of the LOXL1 gene, which is essential for elastin synthesis. Promoter studies showed that the minor "C" allele had significantly greater activity than the major "A" allele. Case-control studies examined the association of the alleles of this single nucleotide polymorphism with pelvic organ prolapse and preterm premature rupture of membranes. When comparing allele frequencies and genotypes in pelvic organ prolapse cases versus controls, no significant associations were found. A case-controls study conducted in African American neonates also found no significant associations between the promoter alleles and perterm premature rupture of membranes. We conclude that a functional single nucleotide polymorphism exists in the promoter region of the LOXL1 gene. Association studies suggest that the promoter single nucleotide polymorphism does not contribute significantly to risk of pelvic organ prolapse of preterm premature rupture of membranes. C1 [Ferrell, Georgia; Lu, Minyan; Stoddard, Paul; Strauss, Jerome F., III; Matthews, Catherine A.] Virginia Commonwealth Univ, Sch Med, Dept Obstet & Gynecol, Richmond, VA USA. [Sammel, Mary D.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Romero, Roberto] Hutzel Hosp, NICHD, Perinatol Res Branch, Detroit, MI 48201 USA. RP Strauss, JF (reprint author), MCV Campus,Sanger Hall,1st Floor,Room 1-071,1101, Richmond, VA 23298 USA. EM jfstrauss@vcu.edu FU National Institutes of Health [R01 HD034612, P60 MD002256]; The March of Dimes; Perinatal Research Branch; Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; SGI fellowship FX This research was supported by National Institutes of Health grants R01 HD034612 and P60 MD002256, The March of Dimes, and the Perinatal Research Branch, Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. GF was the recipient of an SGI fellowship for medical Students. NR 36 TC 21 Z9 22 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD MAY PY 2009 VL 16 IS 5 BP 438 EP 446 DI 10.1177/1933719108330567 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 435GX UT WOS:000265333200003 PM 19182211 ER PT J AU Volkow, ND AF Volkow, Nora D. TI Substance Use Disorders in Schizophrenia - Clinical Implications of Comorbidity SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material DE schizophrenia; substance use disorders; comorbidity ID NICOTINE DEPENDENCE; ABUSE; DIAGNOSIS; SMOKING; ASSOCIATION; ADDICTION; PSYCHOSIS; ALCOHOL; ILLNESS; PEOPLE AB Nearly half of the people suffering from schizophrenia also present with a lifetime history of substance use disorders (SUD), a rate that is much higher than the one seen among unaffected individuals. This phenomenon suggests that the factors influencing SUD risk in schizophrenia may be more numerous and/or complex than those modulating SUD risk in the general population. It is critically important to address this comorbidity because SUD in schizophrenic patients is associated with poorer clinical outcomes and contributes significantly to their morbidity and mortality. C1 NIDA, Off Director, NIH, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), NIDA, Off Director, NIH, 6001 Execut Blvd,Room 5274,MSC 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 29 TC 63 Z9 63 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2009 VL 35 IS 3 BP 469 EP 472 DI 10.1093/schbul/sbp016 PG 4 WC Psychiatry SC Psychiatry GA 434MC UT WOS:000265277800001 PM 19325163 ER PT J AU Rietschel, M Georgi, A Schmael, C Schirmbeck, F Strohmaier, J Boesshenz, KV Schwarz, M Nothen, MM Schulze, TG AF Rietschel, Marcella Georgi, Alexander Schmael, Christine Schirmbeck, Frederike Strohmaier, Jana Boesshenz, Katja V. Schwarz, Markus Noethen, Markus M. Schulze, Thomas G. TI Premorbid adjustment: A phenotype highlighting a distinction rather than an overlap between schizophrenia and bipolar disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT 15th Congress on Psychiatric Genetics CT 15th World Congress on Psychiatric Genetics CY OCT 06-11, 2007 CY 2007 CL New York, NY CL New York, NY DE Premorbid functioning; Manic-depressive illness; Psychosocial factors; Schizophrenia; Depression; Psychosis ID I AFFECTIVE-DISORDER; 1ST HOSPITALIZATION; ONSET; LINKAGE; PSYCHOSIS; ILLNESS; SCALE; AGE; ASSOCIATION; PSYCHIATRY AB Background: Premorbid adjustment (PMA) in schizophrenia (SZ) has been widely studied and shown to be worse in individuals who develop SZ as compared to controls. It has been proposed as a predictor of clinical presentation and outcome, and may delineate a specific SZ phenotype for genetic and other biological studies. Research into PMA in BD has been scarce and inconclusive. Aims: The authors compared PMA in individuals suffering from BD with that of healthy controls and investigated whether levels of PMA in BD patients correlate with specific phenotypic features. Methods: The authors investigated 344 BD patients and 137 population-based controls. Retrospective PMA assessment was performed using the Premorbid Adjustment Scale (PAS). An overall score as well as sub-scores for age ranges and functional domains were obtained. Results: Patients had a better overall PAS score than controls and outperformed controls during early and late adolescence. They scored significantly better than controls in the functional domains "sociability and withdrawal" and "adaptation to school". No differences were observed for the other subscales and there were no differences between groups during childhood. No association was observed between PMA and any of the phenotype characteristics investigated. Conclusions: In the largest study to date on PMA in BD, PMA was shown to be better in bipolar patients than in healthy controls. PMA in BD is not a simple proxy for commonly studied phenotypic markers of severity. PMA emerges as a phenotype in its own right, and highlights an aspect of disparity rather than overlap between SZ and BD. (c) 2009 Published by Elsevier B.V. C1 [Rietschel, Marcella; Georgi, Alexander; Schmael, Christine; Schirmbeck, Frederike; Strohmaier, Jana; Boesshenz, Katja V.; Schulze, Thomas G.] Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Schwarz, Markus] Psychiat Zentrum Nordbaden, Wiesloch, Germany. [Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany. RP Schulze, TG (reprint author), NIMH, Clin Res Unit Genet Basis Mood & Anxiety Disorder, NIH, 35 Convent Dr,Bldg 35,Rm 1A205,MSC 3719, Bethesda, MD 20892 USA. EM schulzet@mail.nih.gov RI Schulze, Thomas/H-2157-2013; Schirmbeck, Frederike/G-8187-2016; OI Georgi, Alexander/0000-0002-1499-8524; Schirmbeck, Frederike/0000-0003-1700-0958; Nothen, Markus/0000-0002-8770-2464 NR 41 TC 8 Z9 8 U1 5 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2009 VL 110 IS 1-3 BP 33 EP 39 DI 10.1016/j.schres.2009.03.007 PG 7 WC Psychiatry SC Psychiatry GA 463MZ UT WOS:000267437600004 PM 19345565 ER PT J AU Skelley, SL Apud, JA Weinberger, DR Elvevag, B Miranda, RA Ullman, MT AF Skelley, Shayna L. Apud, Jose A. Weinberger, Daniel R. Elvevag, Brita Miranda, Robbin A. Ullman, Michael T. TI Where words fail, music speaks: Isolated memory processes in a musical patient with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Letter ID LANGUAGE; BRAIN C1 [Skelley, Shayna L.; Apud, Jose A.; Weinberger, Daniel R.; Elvevag, Brita] NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Miranda, Robbin A.; Ullman, Michael T.] Georgetown Univ, Brain & Language Lab, Dept Neurosci, Washington, DC 20057 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM brita@elvevaag.net OI Coburn, Shayna/0000-0001-9526-3580 FU Intramural NIH HHS [Z01 MH002712-13] NR 10 TC 0 Z9 0 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2009 VL 110 IS 1-3 BP 197 EP 199 DI 10.1016/j.schres.2009.02.015 PG 3 WC Psychiatry SC Psychiatry GA 463MZ UT WOS:000267437600025 PM 19304456 ER PT J AU Fasano, RE Bergen, DC AF Fasano, Rebecca E. Bergen, Donna C. TI Intractable epilepsy in patients treated for childhood acute lymphocytic leukemia SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE Leukemia; Methotrexate; Cytosine arabinoside; Intractable epilepsy; Cranial irradiation ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BRAIN IRRADIATION; DENTATE GYRUS; METHOTREXATE; RADIATION; SEIZURES; RAT; NEUROTOXICITY; CHILDREN; CANCER AB Purpose: In the 1970s and 80s, standard treatment for childhood acute lymphocytic leukemia (ALL) included both intrathecal methotrexate and whole-brain irradiation. During acute treatment, seizures were not uncommon. The development of intractable epilepsy years after treatment, however, has not been well described in the literature. We describe five patients who were treated for acute lymphocytic leukemia as children, who later developed intractable epilepsy. Results: All of the patients were diagnosed with leukemia before age seven. Treatment included both whole-brain irradiation and intrathecal chemotherapy. All five received intrathecal methotrexate: in addition, two also received intrathecal cytosine arabinoside. The first seizure occurred at a mean of 7.5 years after diagnosis. Four patients have multiple seizure types, and all patients have been on multiple antiepileptic drugs. All five patients are cognitively impaired. Conclusions: Successful treatment for childhood leukemia may be followed by signs of late cerebral injury including intractable epilepsy. We propose that neurotoxicity resulting from exposure to intrathecal methotrexate and cranial irradiation may have contributed to the intractable epilepsy seen in our five patients. Published by Elsevier Ireland Ltd on behalf of British Epilepsy Association. C1 [Fasano, Rebecca E.; Bergen, Donna C.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. RP Fasano, RE (reprint author), NIH, 10 Ctr Dr,7-5680 MSC 1404, Bethesda, MD 20892 USA. EM fasanore@ninds.nih.gov NR 25 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD MAY PY 2009 VL 18 IS 4 BP 298 EP 302 DI 10.1016/j.seizure.2008.10.008 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 437CY UT WOS:000265465000013 PM 19041267 ER PT J AU Kurland, BF Johnson, LL Egleston, BL Diehr, PH AF Kurland, Brenda F. Johnson, Laura L. Egleston, Brian L. Diehr, Paula H. TI Longitudinal Data with Follow-up Truncated by Death: Match the Analysis Method to Research Aims SO STATISTICAL SCIENCE LA English DT Article DE Censoring; generalized estimating equations; longitudinal data; missing data; quality of life; random effects models; truncation by death ID SELF-RATED HEALTH; QUALITY-OF-LIFE; CAUSAL INFERENCE; PRINCIPAL STRATIFICATION; OLDER-ADULTS; DROP-OUT; POTENTIAL OUTCOMES; MISSING DATA; MODELS; SURVIVAL AB Diverse analysis approaches have been proposed to distinguish data missing due to death from nonresponse, and to summarize trajectories of longitudinal data truncated by death. We demonstrate how these analysis approaches arise from factorizations of the distribution of longitudinal data and survival information. Models are illustrated using cognitive functioning data for older adults. For unconditional models, deaths do not occur, deaths are independent of the longitudinal response, or the unconditional longitudinal response is averaged over the survival distribution. Unconditional models, such as random effects models fit to unbalanced data, may implicitly impute data beyond the time of death. Fully conditional models stratify the longitudinal response trajectory by time of death. Fully conditional models are effective for describing individual trajectories, in terms of either aging (age, or years from baseline) or dying (years from death). Causal models (principal stratification) as currently applied are fully conditional models, since group differences at one timepoint are described for a cohort that will survive past a later timepoint. Partly conditional models summarize the longitudinal response in the dynamic cohort of survivors. Partly conditional models are serial cross-sectional snapshots of the response, reflecting the average response in survivors at a given timepoint rather than individual trajectories. Joint models of survival and longitudinal response describe the evolving health status of the entire cohort. Researchers using longitudinal data should consider which method of accommodating deaths is consistent with research aims, and use analysis methods accordingly. C1 [Johnson, Laura L.] NIH, Off Clin & Regulatory Affairs, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Diehr, Paula H.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Diehr, Paula H.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. EM bkurland@fhcrc.org; johnslau@mail.nih.gov; Brian.Egleston@fccc.edu; pdiehr@u.washington.edu OI Kurland, Brenda/0000-0002-5669-0595 FU Commonwealth of Pennsylvania NIH [P30 CA 06927]; National Heart, Lung, and Blood Institute, with additional contribution National Institute of Neurological Disorders and Stroke [U01 HL080295]; [N01-HC85079]; [N01-HC-85086]; [N01-HC-35129]; [N01 HC-15103]; [N01 HC-55222]; [N01-HC-75150]; [N01-HC45133] FX This research was supported in part by the Intramural Research Program of the NIH, by NIH Grant P30 CA 06927 and by an appropriation from the Commonwealth of Pennsylvania. Research reported in this article was supported by contract numbers N01-HC85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC45133, Grant number U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 45 TC 56 Z9 56 U1 1 U2 16 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 2009 VL 24 IS 2 BP 211 EP 222 DI 10.1214/09-STS293 PG 12 WC Statistics & Probability SC Mathematics GA 550XF UT WOS:000274166300003 PM 20119502 ER PT J AU Lan, KKG Hu, P Proschan, MA AF Lan, K. K. Gordon Hu, Peter Proschan, Michael A. TI A Conditional Power Approach to the Evaluation of Predictive Power SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Clinical trials; Early termination; Interim analysis; Monitoring; Sample size AB In the 1960s and 1970s, almost all clinical trials were designed with a single efficacy analysis at the end. Despite this design, many NIH-sponsored clinical trials were reviewed periodically by Policy Advisory Boards (now called Data and Safety Monitoring Boards). At these reviews, clinicians on the Board often asked: "If the current trend continues, what is the chance that we will have a positive study at the end?" We discuss how to put this question into a statistical framework and provide a simple answer. The "chance" is called conditional power (CP) or predictive power (PP). We discuss the use of CP and PP for early termination of a clinical trial. The concepts of CP and PP can also be applied to sample size determination for a new study or reestimation of sample size in an adaptive design. C1 [Lan, K. K. Gordon; Hu, Peter] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ 08869 USA. [Proschan, Michael A.] NIAID, Bethesda, MD 20892 USA. RP Lan, KKG (reprint author), Johnson & Johnson Pharmaceut Res & Dev LLC, 920 Route 202, Raritan, NJ 08869 USA. EM glan@its.jnj.com NR 8 TC 7 Z9 7 U1 1 U2 8 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD MAY PY 2009 VL 1 IS 2 BP 131 EP 136 DI 10.1198/sbr.2009.0035 PG 6 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA V17ZJ UT WOS:000207974800002 ER PT J AU Celnik, P Paik, NJ Vandermeeren, Y Dimyan, M Cohen, LG AF Celnik, Pablo Paik, Nam-Jong Vandermeeren, Yves Dimyan, Michael Cohen, Leonardo G. TI Effects of Combined Peripheral Nerve Stimulation and Brain Polarization on Performance of a Motor Sequence Task After Chronic Stroke SO STROKE LA English DT Article DE stroke; rehabilitation; transcranial direct current stimulation; nerve stimulation ID PAIRED ASSOCIATIVE STIMULATION; RANDOMIZED CONTROLLED-TRIAL; SOMATOSENSORY STIMULATION; DC-STIMULATION; AFFERENT STIMULATION; CORTEX; EXCITABILITY; RECOVERY; NEUROREHABILITATION; MODULATION AB Background and Purpose-Recent work demonstrated that application of peripheral nerve and cortical stimulation independently can induce modest improvements in motor performance in patients with stroke. The purpose of this study was to test the hypothesis that combining peripheral nerve stimulation (PNS) to the paretic hand with anodal direct current stimulation (tDCS) to the ipsilesional primary motor cortex (M1) would facilitate beneficial effects of motor training more than each intervention alone or sham (tDCS(Sham) and PNS(Sham)). Methods-Nine chronic stroke patients completed a blinded crossover designed study. In separate sessions, we investigated the effects of single applications of PNS+tDCS, PNS+tDCS(Sham), tDCS+PNS(Sham), and PNS(Sham)+tDCS(Sham) before motor training on the ability to perform finger motor sequences with the paretic hand. Results-PNS+tDCS resulted in a 41.3% improvement in the number of correct key presses relative to PNS(Sham)+tDCS(Sham), 15.4% relative to PNS+tDCS(Sham), and 22.7% relative to tDCS+PNS(Sham). These performance differences were maintained 1 and 6 days after the end of the training. Conclusions-These results indicate that combining PNS with tDCS can facilitate the beneficial effects of training on motor performance beyond levels reached with each intervention alone, a finding of relevance for the neurorehabilitation of motor impairments after stroke. (Stroke. 2009; 40: 1764-1771.) C1 [Celnik, Pablo; Paik, Nam-Jong; Vandermeeren, Yves; Dimyan, Michael; Cohen, Leonardo G.] Natl Inst Neurol Disorders & Stroke, Human Cort Physiol & Stroke Neurorehabil Sect, Natl Inst Hlth, Bethesda, MD USA. [Celnik, Pablo] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA. [Paik, Nam-Jong] Seoul Natl Univ, Coll Med, Bundang Hosp, Dept Rehabil Med, Seoul, South Korea. [Vandermeeren, Yves] Univ Catholique Louvain, Clin Univ UCL Mont Godinne, Dept Neurol, Louvain, Belgium. RP Celnik, P (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Phipps 181, Baltimore, MD 21287 USA. EM pcelnik@jhmi.edu RI Paik, Nam-Jong/D-5798-2012; OI Dimyan, Michael/0000-0002-9715-9741 FU NINDS; NIH, USA; American Heart Association [0665347U]; NCMRR; NICHD; NIH [R01HD053793]; Rehabilitation Medicine Scientist Training Program [5K12HD001097] FX This research was supported by the intramural research program of NINDS, NIH, USA. P. Celnik was supported by the American Heart Association (0665347U), NCMRR, NICHD, NIH (R01HD053793) and the Rehabilitation Medicine Scientist Training Program (RMSTP; 5K12HD001097). NR 44 TC 86 Z9 96 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2009 VL 40 IS 5 BP 1764 EP 1771 DI 10.1161/STROKEAHA.108.540500 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 438UB UT WOS:000265579800037 PM 19286579 ER PT J AU MacDonald, IM Russell, L Chan, CC AF MacDonald, Ian M. Russell, Laurie Chan, Chi-Chao TI Choroideremia: New Findings from Ocular Pathology and Review of Recent Literature SO SURVEY OF OPHTHALMOLOGY LA English DT Article DE choroideremia; histopathology; mutation analysis; retinal degeneration ID FACTOR-H POLYMORPHISM; MACULAR DEGENERATION; PIGMENT-EPITHELIUM; BRUCHS MEMBRANE; FEMALE CARRIER; GENE; PATHOGENESIS; DISEASE; RETINA; PHOTORECEPTORS AB Histopathology of young individuals affected by choroideremia is rarely available to allow correlation with the clinical presentation. A 30-year-old man with choroideremia died in a motor vehicle accident and one eye was subjected to histopathological examination. Immunoblot analysis of protein derived from white blood cells of a living brother, also affected with choroideremia, confirmed the absence of Rab escort prolein-1, the normal CHM gene product. Direct sequencing of the coding region and adjacent splice sites of the CHM gene was undertaken on genomic DNA from the living brother and revealed a transition mutation, C to T. in exon 6 (R253X) which resulted in a stop codon and was predicted to truncate the protein product. Histopathological examination of the eye of the deceased brother showed relative independent degeneration of choriocapillaris. retinal pigment epithelium, and retina, similar to observations in the mouse model of choroideremia. In addition, mild T-lymphocytic infiltration was found within the choroid. The ophthalmic features and the pathology of choroideremia are discussed in light of new findings in the current case. (Surv Ophthalmol 54:401-407, 2009. (c) 2009 Elsevier Inc. All rights reserved.) C1 [MacDonald, Ian M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. [Russell, Laurie] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP MacDonald, IM (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10N226,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. OI MacDonald, Ian/0000-0001-7472-8385 FU Intramural NIH HHS [, NIH0011371610]; PHS HHS [NIH0011371610] NR 47 TC 35 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2009 VL 54 IS 3 BP 401 EP 407 DI 10.1016/j.survophthal.2009.02.008 PG 7 WC Ophthalmology SC Ophthalmology GA 446VX UT WOS:000266150700007 PM 19422966 ER PT J AU Schneider, AB Viana, MAG Ron, E AF Schneider, Arthur B. Viana, Marlos A. G. Ron, Elaine TI Weighing Shadows: Can Meta-Analysis Help Define the Risk-Benefit Ratio of RAI Treatment for Low-Risk Thyroid Cancer Patients? SO THYROID LA English DT Editorial Material ID 2ND PRIMARY MALIGNANCIES; WEAKNESSES; STRENGTHS C1 [Schneider, Arthur B.] Univ Illinois, Dept Med, Sect Endocrinol Diabet & Metab, Coll Med, Chicago, IL 60612 USA. [Ron, Elaine] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Viana, Marlos A. G.] Univ Illinois, Coll Pharm, Chicago, IL 60612 USA. RP Schneider, AB (reprint author), Univ Illinois, Dept Med, Sect Endocrinol Diabet & Metab, Coll Med, 1819 W Polk MC 640, Chicago, IL 60612 USA. EM abschnei@uic.edu NR 6 TC 3 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2009 VL 19 IS 5 BP 435 EP 436 DI 10.1089/thy.2009.0091 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 441QB UT WOS:000265782800003 PM 19415992 ER PT J AU Immenschuh, S Naidu, S Chavakis, T Beschmann, H Ludwig, RJ Santoso, S AF Immenschuh, Stephan Naidu, Srivatsava Chavakis, Triantafyllos Beschmann, Heike Ludwig, Ralf J. Santoso, Sentot TI Junctional adhesion molecule (JAM)-C expression is transcriptionally induced in activated T cells SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 23rd European Immunogenetics and Histocompatibility Conference CY MAY 09-12, 2009 CL Ulm, GERMANY C1 [Immenschuh, Stephan] Inst Transfus Med, Hannover, Germany. [Naidu, Srivatsava; Santoso, Sentot] Univ Giessen, Inst Clin Immunol & Transfus Med, D-6300 Giessen, Germany. [Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Beschmann, Heike] Dept Dermatol, Frankfurt, Germany. [Ludwig, Ralf J.] Dept Dermatol, Lubeck, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2009 VL 73 IS 5 BP 407 EP 407 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 445EJ UT WOS:000266032200057 ER PT J AU Hollenbach, JA Erlich, H Feolo, M Fernandez-Vina, M Maiers, M Maldonado-Torres, H Meyer, D Middleton, D Single, R Thomson, G Mack, SJ AF Hollenbach, Jill A. Erlich, Henry Feolo, Michael Fernandez-Vina, Marcelo Maiers, Martin Maldonado-Torres, Hazael Meyer, Diogo Middleton, Derek Single, Rich Thomson, Glenys Mack, Steven J. TI The Immunogenomics Data Analysis Working Group SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 23rd European Immunogenetics and Histocompatibility Conference CY MAY 09-12, 2009 CL Ulm, GERMANY C1 [Hollenbach, Jill A.; Mack, Steven J.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. [Erlich, Henry] Roche Mol Syst, Pleasanton, CA USA. [Feolo, Michael] NIH, Bethesda, MD 20892 USA. [Fernandez-Vina, Marcelo] Univ Texas Houston, Houston, TX USA. [Maiers, Martin] Natl Marrow Donor Program, Minneapolis, MN USA. [Maldonado-Torres, Hazael] Royal Free Hosp, London NW3 2QG, England. [Meyer, Diogo] Univ Sao Paulo, Sao Paulo, Brazil. [Middleton, Derek] City Hosp, Belfast, Antrim, North Ireland. [Single, Rich] Univ Vermont, Burlington, VT USA. [Thomson, Glenys] Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD MAY PY 2009 VL 73 IS 5 BP 468 EP 468 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 445EJ UT WOS:000266032200209 ER PT J AU Eyster, CA Higginson, JD Huebner, R Porat-Shliom, N Weigert, R Wu, WW Shen, RF Donaldson, JG AF Eyster, Craig A. Higginson, Jason D. Huebner, Robert Porat-Shliom, Natalie Weigert, Roberto Wu, Wells W. Shen, Rong-Fong Donaldson, Julie G. TI Discovery of New Cargo Proteins that Enter Cells through Clathrin-Independent Endocytosis SO TRAFFIC LA English DT Article DE Arf6; CD44; CD55; CD98; CD147; clathrin-independent endocytosis; emmprin; glucose transporter 1; Glut1; non-clathrin endocytosis; 4F2 ID PLASMA-MEMBRANE; RECYCLING PATHWAY; MASS-SPECTROMETRY; UNIQUE PLATFORM; LABEL-FREE; TRANSPORT; ARF6; QUANTIFICATION; IDENTIFICATION; STIMULATION AB Clathrin-independent endocytosis (CIE) allows internalization of plasma membrane proteins lacking clathrin-targeting sequences, such as the major histocompatibility complex class I protein (MHCI), into cells. After internalization, vesicles containing MHCI fuse with transferrin-containing endosomes generated from clathrin-dependent endocytosis. In HeLa cells, MHCI is subsequently routed to late endosomes or recycled back out to the plasma membrane (PM) in distinctive tubular carriers. Arf6 is associated with endosomal membranes carrying CIE cargo and expression of an active form of Arf6 leads to the generation of vacuolar structures that trap CIE cargo immediately after endocytosis, blocking the convergence with transferrin-containing endosomes. We isolated these trapped vacuolar structures and analyzed their protein composition by mass spectrometry. Here we identify and validate six new endogenous cargo proteins (CD44, CD55, CD98, CD147, Glut1, and ICAM1) that use CIE to enter cells. CD55 and Glut1 appear to closely parallel the trafficking of MHCI, merging with transferrin endosomes before entering the recycling tubules. In contrast, CD44, CD98, and CD147 appear to directly enter the recycling tubules and by-pass the merge with EEA1-positive, transferrin-containing endosomes. This divergent itinerary suggests that sorting may occur along this CIE pathway. Furthermore, the identification of new cargo proteins will assist others studying CIE in different cell types and tissues. C1 [Eyster, Craig A.; Higginson, Jason D.; Huebner, Robert; Porat-Shliom, Natalie; Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Porat-Shliom, Natalie] Tel Aviv Univ, Dept Neurobiochem, IL-69978 Tel Aviv, Israel. [Weigert, Roberto] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Wu, Wells W.; Shen, Rong-Fong] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov FU Intramural Research Program of the National Heart, Lung and Blood Institute, NIH FX JDH was a fellow in the National Capitol Consortium Neonatal-Perinatal Fellowship Program, Department of Pediatrics, Uniformed Services University and National Naval Medical Center, Bethesda, MD 20814. For JDH, the views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the US Government. NR 35 TC 84 Z9 85 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD MAY PY 2009 VL 10 IS 5 BP 590 EP 599 DI 10.1111/j.1600-0854.2009.00894.x PG 10 WC Cell Biology SC Cell Biology GA 431QM UT WOS:000265077900011 PM 19302270 ER PT J AU Neckers, L Mollapour, M Tsutsumi, S AF Neckers, Len Mollapour, Mehdi Tsutsumi, Shinji TI The complex dance of the molecular chaperone Hsp90 SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ESCHERICHIA-COLI HSP90; ATPASE CYCLE; CONFORMATIONAL DYNAMICS; CANCER; INHIBITORS; MACHINERY; STATES; TARGET AB Hsp90 chaperone function requires traversal of a nucleotide-dependent conformational cycle, but the slow and variable rate of Hsp90-mediated ATP hydrolysis is difficult to envision as a determinant of conformational change. A recent study solves this dilemma by showing that Hsp90 samples multiple conformational states in the absence of nucleotides, which serve to influence, but not direct, the cycle. The conformational program of Hsp90 is conserved from bacteria to humans, although the population dynamics are species specific. C1 [Neckers, Len; Mollapour, Mehdi; Tsutsumi, Shinji] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 23 TC 27 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAY PY 2009 VL 34 IS 5 BP 223 EP 226 DI 10.1016/j.tibs.2009.01.006 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 455DB UT WOS:000266736000002 PM 19359180 ER PT J AU Martin, B Maudsley, S White, CM Egan, JM AF Martin, Bronwen Maudsley, Stuart White, Caitlin M. Egan, Josephine M. TI Hormones in the naso-oropharynx: endocrine modulation of taste and smell SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID GLUCAGON-LIKE PEPTIDE-1; VASOACTIVE-INTESTINAL-PEPTIDE; RAT OLFACTORY-BULB; LEPTIN RECEPTOR; NEUROPEPTIDE-Y; SWEET TASTE; CIRCUMVALLATE PAPILLAE; ULTRASTRUCTURAL-LOCALIZATION; COEXPRESSION PATTERNS; POSITIONAL CLONING AB Olfaction and gustation are important sensory modalities for locating food and for determining which foodstuffs to ingest. It is becoming apparent that there is a strong link between olfaction, gustation and metabolic control. Because endocrine signaling in the naso-oropharynx is likely to influence food intake, satiety and general metabolic control, it is important to examine some of the major hormones that play an integral part in energy homeostasis. Here, we provide an overview of the main endocrine factors known to be present in the naso-oropharynx and discuss their functional roles in maintaining metabolic function. Gaining a greater appreciation of how flavor perception is linked to peripheral metabolism could lead to novel therapeutic strategies for obesity and lifestyle-related diseases. C1 [Egan, Josephine M.] NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Martin, Bronwen; White, Caitlin M.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Intramural Res Program, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Clin Invest Lab, Intramural Res Program, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 FU National Institute on Aging, NIH FX These authors are supported by the Intramural Research Program of the National Institute on Aging, NIH. We thank Jimmy Burrill for his expert assistance with the artwork for the figures. NR 77 TC 22 Z9 24 U1 1 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 2009 VL 20 IS 4 BP 163 EP 170 DI 10.1016/j.tem.2009.01.006 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 446VC UT WOS:000266148500003 PM 19359194 ER PT J AU van Praag, H AF van Praag, Henriette TI Exercise and the brain: something to chew on SO TRENDS IN NEUROSCIENCES LA English DT Review ID ADULT HIPPOCAMPAL NEUROGENESIS; ENHANCED SYNAPTIC PLASTICITY; GENERATED GRANULE CELLS; DECREASES AMYLOID LOAD; LONG-TERM POTENTIATION; MOUSE DENTATE GYRUS; PHYSICAL-ACTIVITY; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; VOLUNTARY EXERCISE AB Evidence is accumulating that exercise has profound benefits for brain function. Physical activity improves learning and memory in humans and animals. Moreover, an active lifestyle might prevent or delay loss of cognitive function with aging or neurodegenerative disease. Recent research indicates that the effects of exercise on the brain can be enhanced by concurrent consumption of natural products such as omega fatty acids or plant polyphenols. The potential synergy between diet and exercise could involve common cellular pathways important for neurogenesis, cell survival, synaptic plasticity and vascular function. Optimal maintenance of brain health might depend on exercise and intake of natural products. C1 NIA, Neuroplast & Behav Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP van Praag, H (reprint author), NIA, Neuroplast & Behav Unit, Neurosci Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. EM vanpraagh@mail.nih.gov RI van Praag, Henriette/F-3939-2015 OI van Praag, Henriette/0000-0002-5727-434X FU Intramural Research Program; National Institutes of Health; National Institute on Aging FX This review was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (www.nia.nih.gov). I thank Mark Mattson for comments on the manuscript, David J. Creer for editorial assistance and K.C. Alexander for figure preparation. NR 103 TC 225 Z9 228 U1 10 U2 84 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAY PY 2009 VL 32 IS 5 BP 283 EP 290 DI 10.1016/j.tins.2008.12.007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 452FB UT WOS:000266524400006 PM 19349082 ER PT J AU Pinto, PA AF Pinto, Peter A. TI Renal carcinoma: minimally invasive surgery of the small renal mass SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Partial nephrectomy; Laparoscopy; Robotic surgery; Kidney neoplasms; Kidney ID LAPAROSCOPIC PARTIAL NEPHRECTOMY; ROBOTIC PARTIAL NEPHRECTOMY; NEPHRON-SPARING SURGERY; CHRONIC KIDNEY-DISEASE; CELL CARCINOMA; RISING INCIDENCE; TUMORS; OUTCOMES AB Open partial nephrectomy has become the gold standard surgical management for small renal masses less than 4 cm. With the Surgical advances in the field of laparoscopy and robotic surgery, minimally invasive partial nephrectomy is now feasible. Long-term 5 year cancer-specific Survival rates have recently been reported for laparoscopic partial nephrectomy. These results are comparable to open partial nephrectomy series. As the field of robotic assisted surgery continues to expand beyond the treatment of prostate cancer, these techniques are being investigated in the treatment of small renal masses. Currently, minimally invasive partial nephrectomy has become an option in the treatment of small renal masses. Published by Elsevier Inc. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX This work was funded by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 21 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2009 VL 27 IS 3 BP 335 EP 336 DI 10.1016/j.urolonc.2008.12.015 PG 2 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 447RW UT WOS:000266210500022 PM 19414126 ER PT J AU Quinten, C Martinelli, F Coens, C Maringwa, J Cleeland, C Fechtner, H Gotay, C Greimel, E King, M Osoba, D Taphoorn, MJB Reeve, B Ringash, J Schmucker-Von Koch, J Weis, J Bottomley, A AF Quinten, C. Martinelli, F. Coens, C. Maringwa, J. Cleeland, C. Fechtner, H. Gotay, C. Greimel, E. King, M. Osoba, D. Taphoorn, M. J. B. Reeve, B. Ringash, J. Schmucker-Von Koch, J. Weis, J. Bottomley, A. TI A METHODOLOGICAL INVESTIGATION TO DEFINE A CLINICALLY RELEVANT CUT-OFF POINT IN THE ORDINAL SCALE OF THE EORTC QLQ-C30 QUESTIONNAIRE SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Quinten, C.; Martinelli, F.; Coens, C.; Maringwa, J.; Bottomley, A.] EORTC, Brussels, Belgium. [Cleeland, C.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fechtner, H.] City Hosp Magdeburg, Magdeburg, Germany. [Gotay, C.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Greimel, E.] Med Univ Graz, Graz, Austria. [King, M.] Univ Sydney, Sydney, NSW 2006, Australia. [Osoba, D.] QOL Consulting, W Vancouver, BC, Canada. [Taphoorn, M. J. B.] VU Univ Med Ctr, Med Ctr Haaglanden, The Hague, Netherlands. [Reeve, B.] NCI, Bethesda, MD 20892 USA. [Ringash, J.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Schmucker-Von Koch, J.] Univ Regensburg, Regensburg, Germany. [Weis, J.] Univ Freiburg, Freiburg, Germany. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2009 VL 12 IS 3 BP A53 EP A53 DI 10.1016/S1098-3015(10)73327-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 433WO UT WOS:000265236700259 ER PT J AU Rasu, R Hunter, C Maruska, H Peterson, A Foreyt, J AF Rasu, R. Hunter, C. Maruska, H. Peterson, A. Foreyt, J. TI ECONOMIC EVALUATION OF AN INTERNET BASED WEIGHT MANAGEMENT PROGRAM SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Maruska, H.] Univ Missouri, Sch Pharm, Kansas City, MO 64110 USA. [Hunter, C.] NIDDK, NIH, Bethesda, MD USA. [Peterson, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Foreyt, J.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY PY 2009 VL 12 IS 3 BP A133 EP A133 DI 10.1016/S1098-3015(10)73728-1 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 433WO UT WOS:000265236700660 ER PT J AU Rao, S Bryant, M Herbert, R Sullivan, N Murray, C Bacher, J Safdar, N AF Rao, S. Bryant, M. Herbert, R. Sullivan, N. Murray, C. Bacher, J. Safdar, N. TI Idiopathic Chondrolysis Condition in Two Young, Wild-caught Cynomolgus Monkeys (Macaca fascicularis) Reared in Captivity SO VETERINARY PATHOLOGY LA English DT Article DE Cynomolgus monkey; femoral head degenerative joint disease; idiopathic chondrolysis; Legg-Calve-Perthes; macaque; osteoarthritis ID HIP AB Idiopathic chondrolysis is a human clinical entity typically reported in adolescent individuals. In this brief communication, we report 2 cases of presumptive idiopathic chondrolysis of the femoral head in Cynomolgus macaques and discuss the clinical symptomatology and pathology of the disease. In detail, we describe the histomorphologic changes of idiopathic chondrolysis and compare these findings with those typically observed in the primary differential diagnoses of Legg-Calve-Perthes disease and nonspecific osteoarthritis. Consideration of this entity among differential diagnoses in young Cynomolgus macaques with unilateral osteoarthritis could be important both for laboratory animal veterinarians and pathologists. C1 [Safdar, N.] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA. [Rao, S.; Sullivan, N.; Murray, C.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Bryant, M.; Herbert, R.; Bacher, J.] NIAID, Div Vet Resources, Off Res Serv, NIH, Bethesda, MD 20892 USA. RP Rao, S (reprint author), 40 Convent Dr,Room 1407, Bethesda, MD 20892 USA. EM sraol@mail.nih.gov FU NIH FX We gratefully acknowledge the contributions of Ms. Alyse Zajac for manuscript coordination and preparation. We also gratefully acknowledge the contributions of Mr. Alphie Cisar for providing animal care; Ms. Brenda Hartman for figure formatting; Ms. Alida Ault, Mr. John-Paul Todd, and Ms. Linda Bessacque for scheduling and technical assistance; Mr. Jorge Chavez and Mr. Erik Lasker for providing gross photographs; Ms. Annie Merriweather and Ms. Kathy Dukes for preparation of histologic tissue sections; and Mr. Rick Dreyfuss for preparation of histologic photographs. This research was supported in part by the Intramural Research Program of the NIH, Vaccine Research Center. NR 13 TC 2 Z9 2 U1 1 U2 1 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAY PY 2009 VL 46 IS 3 BP 509 EP 513 DI 10.1354/vp.08-VP-0216-R-BC PG 5 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 443JY UT WOS:000265907200018 PM 19176502 ER PT J AU Burbelo, PD Issa, AT Ching, KH Exner, M Drew, WL Alter, HJ Iadarola, MJ AF Burbelo, Peter D. Issa, Alexandra T. Ching, Kathryn H. Exner, Maurice Drew, W. Lawrence Alter, Harvey J. Iadarola, Michael J. TI Highly quantitative serological detection of anti-cytomegalovirus (CMV) antibodies SO VIROLOGY JOURNAL LA English DT Article ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; T-LYMPHOCYTE SUBPOPULATIONS; CRITICALLY-ILL PATIENTS; CYTOMEGALOVIRUS-INFECTION; SURGICAL-PATIENTS; ASSAY; DIAGNOSIS; IMMUNE; AUTOANTIBODIES; REACTIVATION AB Background: Human cytomegalovirus infection is associated with a variety of pathological conditions including retinitis, pneumonia, hepatitis and encephalitis that may be transmitted congenitally, horizontally and parenterally and occurs both as a primary infection and as reactivation in immunocompromised individuals. Currently, there is a need for improved quantitative serological tests to document seropositivity with high sensitivity and specificity. Methods: Here we investigated whether luciferase immunoprecipitation systems (LIPS) would provide a more quantitative and sensitive method for detecting anti-CMV antibodies. Four protein fragments of immunodominant regions of CMV antigens pp150 and pp65 were generated as Renilla luciferase (Ruc) fusion proteins and used in LIPS with two cohorts of CMV positive and negative sera samples previously tested by ELISA. Results: Analysis of the antibody responses to two of these antigen fragments, pp150-d1 and pp150-d2, revealed geometric mean antibody titers in the first cohort that were 100-1000 fold higher in the CMV positive sera compared to the CMV negative samples (p < 0.0001) and infection status exactly matched the ELISA results for the 46 samples of the first cohort (100% sensitivity and 100% specificity). Two additional antigen fragments, pp65-d1 and pp65-d2 also showed robust antibody titers in some CMV-infected sera and yielded 50% and 96% sensitivity, respectively. Analysis of a second cohort of 70 samples using a mixture of the 4 antigens, which simplifies data collection and analysis, yielded values which correlated well with the sum of the values from the 4 separate tests (r(s) = 0.93, p < 0.00001). While comparison of the LIPS results from this second cohort with ELISA showed 100% sensitivity, LIPS detected six additional CMV positive samples that were not detected by ELISA. Heat map analysis revealed that several of the LIPS positive/ELISA negative samples had positive LIPS immunoreactivity with 3-4 of the CMV antigens. Conclusion: These results suggest that LIPS provides a highly robust and quantitative method for studying anti-CMV antibodies and has the potential to more accurately document CMV infection than standard ELISA. C1 [Burbelo, Peter D.; Issa, Alexandra T.; Ching, Kathryn H.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Exner, Maurice] Focus Diagnost Inc, Cypress, CA 90630 USA. [Drew, W. Lawrence] Univ Calif San Francisco, Med Ctr Mt Zion, San Francisco, CA 94115 USA. [Alter, Harvey J.] NIH, Ctr Clin, Infect Dis Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Burbelo, PD (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. EM burbelop@nidcr.nih.gov; Issaa@mail.nih.gov; ChingK@mail.nih.gov; mexner@focusdx.com; Lawrence.Drew@clinlab.ucsfmedctr.org; halter@nih.gov; iadarola@nih.gov FU National Institute of Dental and Craniofacial Research FX This study was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research. NR 32 TC 11 Z9 11 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 1 PY 2009 VL 6 AR 45 DI 10.1186/1743-422X-6-45 PG 8 WC Virology SC Virology GA 452IP UT WOS:000266534000001 PM 19409090 ER PT J AU McNeil, SE AF McNeil, Scott E. TI Nanoparticle therapeutics: a personal perspective SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID DRUG-DELIVERY; DENDRIMERS; BIODISTRIBUTION; NANOMATERIALS; PARTICLES; MICE AB Nanotechnology offers many potential benefits to cancer research through passive and active targeting, increased solubility/bioavailablility, and novel therapies. However, preclinical characterization of nanoparticles is complicated by the variety of materials, their unique surface properties, reactivity, and the task of tracking the individual components of multicomponent, multifunctional nanoparticle therapeutics in in vivo studies. There are also regulatory considerations and scale-up challenges that must be addressed. Despite these hurdles, cancer research has seen appreciable improvements in efficacy and quite a decrease in the toxicity of chemotherapeutics because of 'nanotech' formulations, and several engineered nanoparticle clinical trials are well underway. This article reviews some of the challenges and benefits of nanomedicine for cancer therapeutics and diagnostics. (C) 2009 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2009 1 264-271 C1 NCI, Nanotechnol Characterizat Lab, Imaging & Nanotechnol Grp, SAIC Frederick Inc, Frederick, MD 21701 USA. RP McNeil, SE (reprint author), NCI, Nanotechnol Characterizat Lab, Imaging & Nanotechnol Grp, SAIC Frederick Inc, Frederick, MD 21701 USA. EM ncl@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute; National Institutes of Health [N01-00-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-00-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply an endorsement by the US Government. The author declares no competing financial interest. The author thanks Dr. Jennifer Hall for her considerable assistance during the preparation of this article. NR 24 TC 80 Z9 81 U1 4 U2 44 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD MAY-JUN PY 2009 VL 1 IS 3 BP 264 EP 271 DI 10.1002/wnan.006 PG 8 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 585PS UT WOS:000276839500002 PM 20049796 ER PT J AU Wang, YL Jiang, Y Yang, D Li, WY Gong, TX Feng, Y Jiang, ZH Li, MY AF Wang, Yueling Jiang, Yan Yang, De Li, Wanyi Gong, Tianxiang Feng, Yan Jiang, Zhonghua Li, Mingyuan TI Purification and characterization of novel antifungal peptide, mouse beta defensin-1, in Escherichia coli SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Mouse beta defensin-1; Functional expression; Fusion protein; Purification; Antifungal activity ID HUMAN BETA-DEFENSIN-2; EXPRESSION; HOMOLOG AB Mouse beta defensin-1 (mBD-1) is a cationic peptide with broad antimicrobial activity. The mBD-1 gene was cloned and fused with TrxA to construct pET32-mBD1, which was transformed into E. coli BL21 (DE3). The optimal expression conditions of fusion protein TrxA-mBD1 were: cultivation at 32A degrees C in 2 x YT medium, induction with 0.2 mM isopropylthio--galactoside (IPTG), and post-induction expression for 8 h. The fusion protein was highly soluble (90.0%) and accounted for 65% of the total soluble protein; and its volumetric productivity reached 0.67 g/l, i.e., 0.14 g/l of recombinant mBD-1. At 5 mu M, purified recombinant mBD-1 killed 50% of Candida albicans. C1 [Li, Mingyuan] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China. [Wang, Yueling; Jiang, Yan; Li, Wanyi; Gong, Tianxiang; Feng, Yan; Jiang, Zhonghua; Li, Mingyuan] Sichuan Univ, Dept Microbiol, W China Sch Preclin & Forens Med, Chengdu 610041, Peoples R China. [Yang, De] NCI, Basic Res Program, SAIC Frederick & Lab Mol Immunoregulat, NCI FCRDC,NIH, Frederick, MD 21702 USA. RP Li, MY (reprint author), Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Sichuan, Peoples R China. EM yuelingwang88@hotmail.com; zxllmyus@yahoo.com FU National Natural Science Foundation of China [30671964] FX This work was supported by a grant from the National Natural Science Foundation of China (No. 30671964). NR 14 TC 1 Z9 1 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD MAY PY 2009 VL 25 IS 5 BP 917 EP 920 DI 10.1007/s11274-009-9956-y PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 430DY UT WOS:000264970200024 ER PT J AU Roccaro, AM Sacco, A Chen, CZ Runnels, J Leleu, X Azab, F Azab, AK Jia, XY Ngo, HT Melhem, MR Burwick, N Varticovski, L Novina, CD Rollins, BJ Anderson, KC Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Chen, Changzhong Runnels, Judith Leleu, Xavier Azab, Feda Azab, Abdel Kareem Jia, Xiaoying Ngo, Hai T. Melhem, Molly R. Burwick, Nicholas Varticovski, Lyuba Novina, Carl D. Rollins, Barrett J. Anderson, Kenneth C. Ghobrial, Irene M. TI microRNA expression in the biology, prognosis, and therapy of Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID NF-KAPPA-B; MULTIPLE-MYELOMA; CELL LYMPHOMAS; TARGET; REVEALS; MIR-155; PATHWAY; PROTEIN; KINASE; CANCER AB Multilevel genetic characterization of Waldenstrom macroglobulinemia (WM) is required to improve our understanding of the underlying molecular changes that lead to the initiation and progression of this disease. We performed microRNA-expression profiling of bone marrow-derived CD19(+) WM cells, compared with their normal cellular counterparts and validated data by quantitative reverse-transcription-polymerase chain reaction (qRT-PCR). We identified a WM-specific microRNA signature characterized by increased expression of microRNA-363*/-206/-494/-155/-184/-542-3p, and decreased expression of microRNA-9* (ANOVA; P < .01). We found that microRNA-155 regulates proliferation and growth of WM cells in vitro and in vivo, by inhibiting MAPK/ERK, PI3/AKT, and NF-kappa B pathways. Potential microRNA-155 target genes were identified using gene-expression profiling and included genes involved in cell-cycle progression, adhesion, and migration. Importantly, increased expression of the 6 miRNAs significantly correlated with a poorer outcome predicted by the International Prognostic Staging System for WM. We further demonstrated that therapeutic agents commonly used in WM alter the levels of the major miRNAs identified, by inducing downmodulation of 5 increased miRNAs and up-modulation of patient-downexpressed miRNA-9*. These data indicate that microRNAs play a pivotal role in the biology of WM; represent important prognostic marker; and provide the basis for the development of new microRNA-based targeted therapies in WM. (Blood. 2009; 113: 4391-4402) C1 [Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, Dept Med Oncol, Boston, MA 02115 USA. [Roccaro, Aldo M.; Sacco, Antonio; Chen, Changzhong; Runnels, Judith; Leleu, Xavier; Azab, Feda; Azab, Abdel Kareem; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Burwick, Nicholas; Novina, Carl D.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Boston, MA USA. [Roccaro, Aldo M.] Univ Bari, Dept Internal Med & Clin Oncol, Sch Med, Bari, Italy. [Roccaro, Aldo M.] Univ Brescia, Sch Med, Unit Blood Dis & Cell Therapies, Brescia, Italy. [Varticovski, Lyuba] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Kirsch Lab Waldenstrom Macroglobulinemia, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 FU NIH [R21 1R21CA126119-01]; International Waldenstrom Macroglobulinemia Foundation (IWMF); Kirsch Laboratory for Waldenstrom Macroglobulinemia; Italian Association for Cancer Research; Berlucchi Foundation FX This work was supported in part by NIH (Washington, DC) grant R21 1R21CA126119-01, International Waldenstrom Macroglobulinemia Foundation (IWMF), Kirsch Laboratory for Waldenstrom Macroglobulinemia, Italian Association for Cancer Research (A. M. R.), and Berlucchi Foundation (A. M. R.). NR 42 TC 62 Z9 66 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 30 PY 2009 VL 113 IS 18 BP 4391 EP 4402 DI 10.1182/blood-2008-09-178228 PG 12 WC Hematology SC Hematology GA 442MW UT WOS:000265846300035 PM 19074725 ER PT J AU Wang, W Jiang, DQ Zhu, YF Liu, W Duan, JH Dai, SL AF Wang, Wen Jiang, Dongqiao Zhu, Yingfen Liu, Wei Duan, Jinhong Dai, Sunling TI Relaxing Effects of Phytoestrogen alpha-Zearalanol on Rat Thoracic Aorta Rings in Vitro SO CHINESE JOURNAL OF PHYSIOLOGY LA English DT Article DE alpha-ZAL; thoracic aortas; vasorelaxation; NO; cGMP; K+ channel; Ca2+ channel ID VEIN ENDOTHELIAL-CELLS; PORCINE CORONARY-ARTERY; RABBIT BASILAR ARTERY; NITRIC-OXIDE; SMOOTH-MUSCLE; INDUCED RELAXATION; 17-BETA-ESTRADIOL; MECHANISMS; CHANNELS; INHIBITION AB The aim of this research is to investigate the vasorelaxing effects and mechanisms involved in the phytoestrogen alpha-zearalanol (alpha-ZAL) in rat thoracic aortas rings. Intact or endothelium denuded rat thoracic aortas rings were put in individual organ chamber to observe the endothelium-dependent or independent vasorelaxing effects of alpha-ZAL (10(-10)-10(-5) M). The thoracic aortas rings were pre-contracted with phenylephrine. The relaxing effects of alpha-ZAL were observed and the influence of N-omega-nitro-L-arginine methylester (L-NAME, NOS inhibitor), methylene blue (MB, guanylate cyclase inhibitor), charybdotoxin (ChTX, Ca2+-activated K+ channel blocker), glibenclamide (ATIP-sensitive K+ channel blocker), (-) BayK8644 (L-type Ca2+ channel agonist) and ICI182,780 (estrogen receptor antagonist) were pre-incubated with alpha-ZAL, respectively, to explore the possible mechanisms involved in this vasorelaxation. Furthermore, the Phospho-eNOS expression and cGMP level in the aortas tissue were detected by Western blot and radioimmunity, respectively; the NO level in perfusate was assaied by chromatometry. Our result showed that alpha-ZAL (10(-10)-10(-5) M) induced both endothelium-dependent and -independent relaxation of rat thoracic aortas rings. The vasorelaxing effects of alpha-ZAL were dose-dependent whether the endothelium was intact or not. In endothelium-intact aortas rings, alpha-ZAL-induced vasorelaxation might be inhibited by L-NAME, MB, charybdotoxin, glibenclamide and (-) BayK8644, but not ICI182,780. (-) BayK86414 could also inhibit alpha-ZAL-induced vasorelaxation in endothelium-denuded aortas rings, 10(-7)-10(-5) M alpha-ZAL might induce the Phospho-eNOS expression in thoracic aorta tissue, increase the NO level in perfusate and cGMP content in thoracic aorta tissue. Meanwhile, L-NAME might decrease both NO and its downstream cGMP level. Methylene blue might decrease the level of cGMP. These results suggest that alpha-ZAL induces a partly endothelium-dependent relaxation of rat thoracic aortas rings; the possible mechanisms involved in this rapid vasorelaxation include activation of eNOS/NO/cGMP pathway, opening of VSMCs ATP-sensitive and Ca2+-activated K+ channels through secretion of EDHF from endothelium. Furthermore, this relaxation also appears to be mediated by both direct and indirect inhibition of voltage-dependent Ca2+ channel of VSMCs, while it is not concerned with activation of estrogen receptor. C1 [Wang, Wen; Jiang, Dongqiao; Zhu, Yingfen] Capital Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Beijing 100069, Peoples R China. [Wang, Wen] SUNY Buffalo, Ctr Res Cardiovasc Med, Buffalo, NY 14214 USA. [Liu, Wei; Duan, Jinhong; Dai, Sunling] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Pathophysiol, New York, NY 10005 USA. [Liu, Wei; Duan, Jinhong; Dai, Sunling] Peking Union Med Coll, New York, NY 10005 USA. [Liu, Wei] NCI, Metab & Canc Susceptibil Sect, Comparat Carcinogenesis Lab, Ctr Canc Res,Natl Inst Hlth, Frederick, MD 21702 USA. RP Jiang, DQ (reprint author), Capital Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Beijing 100069, Peoples R China. EM jiangdq2005@hotmail.com FU Natural Science Foundation of China [30700293]; Beijing Natural Science Foundation [7082013]; Natural Science Foundation of Capital Medical University [2006ZR04]; Beijing Municipality FX This work was supported by the Natural Science Foundation of China (30700293), Beijing Natural Science Foundation (7082013), Natural Science Foundation of Capital Medical University (2006ZR04) and Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality.; We thank Professor Jilun Li and Professor Fanjing Meng (Institute of Biological Sciences, Chinese University of Agriculture, Beijing) for their having provided purified alpha-zearalanol and their initiatives on its capacity as the endogenous phytohormone. NR 27 TC 8 Z9 9 U1 0 U2 3 PU CHINESE PHYSIOLOGICAL SOC PI TAIPEI PA NATL YANG-MING UNIV, TAIPEI, TAIWAN SN 0304-4920 J9 CHINESE J PHYSIOL JI Chin. J. Physiol. PD APR 30 PY 2009 VL 52 IS 2 BP 99 EP 105 DI 10.4077/CJP.2009.AMH006 PG 7 WC Physiology SC Physiology GA 437EJ UT WOS:000265468800006 PM 19764345 ER PT J AU Buerlein, RC Hyde, TM Lipska, BK Robinson, W Khosla, A Kleinman, JE AF Buerlein, Ross C. Hyde, Thomas M. Lipska, Barbara K. Robinson, Wilton Khosla, Anchal Kleinman, Joel E. TI A comparison of human brain dissection by drill versus saw on nucleic acid quality SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE DNA; RNA; Postmortem; Dissection; Cerebellum ID GENE-EXPRESSION; RNA AB This study examined the effect of two dissection techniques on the quality of human brain specimens. Frozen cerebellar samples were obtained from postmortem brains of 10 subjects free from neurological and psychiatric disease. These tissues were tested for RNA and DNA concentration and quality after being dissected with either an electric dental drill or a small handsaw. RNA and DNA were extracted separately from each sample, and the concentrations and quality of each were measured. We found that dissection technique does not significantly affect RNA or DNA quality/yield. RNA and DNA yields, as well as RNA integrity showed no significant differences between the two dissection techniques. Therefore, these results support the use of a high-speed hand-held electric dental drill as an efficient and anatomically precise means of human brain dissection without compromising tissue quality. Published by Elsevier B.V. C1 [Buerlein, Ross C.; Hyde, Thomas M.; Lipska, Barbara K.; Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. [Robinson, Wilton] Morehouse Coll, Atlanta, GA 30034 USA. [Khosla, Anchal] Coll William & Mary, Williamsburg, VA 22079 USA. RP Hyde, TM (reprint author), NIMH, Clin Brain Disorders Branch, Bldg 10,Room 4N306,10 Ctr Dr Bethesda, Bethesda, MD 20892 USA. EM buerleinr@mail.nih.gov; hydet@mail.nih.gov; lipskab@intra.nimh.nih.gov; joel.kleinman@mail.nih.gov FU NIMH-COR [MH-16573]; National Institutes of Health-National Institute of Mental Health FX This research was supported in part by NIMH-COR Grant # MH-16573. This work was supported by the Intramural Program of the National Institutes of Health-National Institute of Mental Health. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2009 VL 179 IS 1 BP 68 EP 70 DI 10.1016/j.jneumeth.2008.12.027 PG 3 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 430RR UT WOS:000265006700011 PM 19167430 ER PT J AU Venable, RM Chen, LE Pastor, RW AF Venable, Richard M. Chen, Linda E. Pastor, Richard W. TI Comparison of the Extended Isotropic Periodic Sum and Particle Mesh Ewald Methods for Simulations of Lipid Bilayers and Monolayers SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; BOUNDARY-CONDITIONS; LIQUID/LIQUID INTERFACES; COMPUTER-SIMULATION; LENNARD-JONES; SURFACE; TENSION; DEPENDENCE; DIFFUSION; ALKANES AB 3D-IPS/DFFT is an extension of the three-dimensional isotropic periodic sum (3D-IPS) for evaluation of electrostatic and Lennard-Jones interactions in heterogeneous systems; it utilizes a discrete fast Fourier transform (DFFT) for efficient calculation of the IPS potential with a large local region radius. The method is demonstrated to be highly accurate for simple bulk fluids, liquid/liquid and liquid/vapor interfaces, and lipid bilayers and monolayers. Values for r(C) (the cutoff distance for direct evaluation of pairs) and R(C) (the local region radius) equal to 10 angstrom and twice the longest edge of the periodic cell, respectively, provide excellent efficiency and accuracy. Dimyristoylphosphatidylcholine (DMPC) monolayers simulated with the CHARMM (Chemistry at HARvard Molecular Mechanics) C27r lipid parameter set and 3D-IPS/DFFT yield Surface tensions approximately 8 dyn/cm higher than those simulated using particle mesh Ewald (PME), and with experiment. In contrast, surface tensions for DMPC bilayers are 16 dyn/cm/leaflet with both 3D-IPS/DFFT (r(C) = 10 and 12 angstrom) and PME (r(C) = 12 angstrom). This indicates that PME (r(C) = 12 angstrom) may be used for simulations of bilayers, but not monolayers, and that the large bilayer surface tension arising from C27r is incorrect. C1 [Venable, Richard M.; Chen, Linda E.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Pastor, RW (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM pastorr@nhlbi.nih.gov FU NIH; National Heart, Lung and Blood Institute FX We thank Xiongwu Wu and Bernard Brooks for helpful discussions. This research Was Supported in part by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. This study utilized the high-performance computational capabilities of the CIT Biowulf and NHLBI LoBoS clusters at the National Institutes of Health, Bethesda, MD. NR 37 TC 35 Z9 36 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 30 PY 2009 VL 113 IS 17 BP 5855 EP 5862 DI 10.1021/jp900843x PG 8 WC Chemistry, Physical SC Chemistry GA 438BC UT WOS:000265529900026 PM 19351117 ER PT J AU Ben-Yaakov, D Andelman, D Harries, D Podgornik, R AF Ben-Yaakov, Dan Andelman, David Harries, Daniel Podgornik, Rudi TI Ions in Mixed Dielectric Solvents: Density Profiles and Osmotic Pressure between Charged Interfaces SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID AQUEOUS-ORGANIC SOLVENTS; PREFERENTIAL HYDRATION; UNCHARGED SOLUTES; PRACTICAL GUIDE; GIBBS ENERGIES; PROTEIN; FORCES; MICROFLUIDICS; EXCLUSION; WATER AB The forces between charged macromolecules, usually given in terms of osmotic pressure, are highly affected by the intervening ionic solution. While in most theoretical studies the solution is treated as a homogeneous structureless dielectric medium, recent experimental studies concluded that, for a bathing solution composed of two solvents (binary mixture), the osmotic pressure between charged macromolecules is affected by the binary solvent composition. By adding local solvent composition terms to the free energy, we obtain a general expression for the osmotic pressure, in planar geometry and within the mean-field framework. The added effect is due to the permeability inhomogeneity and nonelectrostatic short-range interactions between the ions and solvents (preferential solvation). This effect is mostly pronounced at small distances and leads to a reduction in the osmotic pressure for macromolecular separations of the order 1-2 nm. Furthermore, it leads to a depletion of one of the two solvents from the charged macromolecules (modeled as planar interfaces). Lastly, by comparing the theoretical results with experimental ones, an explanation based on preferential solvation is offered for recent experiments on the osmotic pressure of DNA solutions. C1 [Ben-Yaakov, Dan; Andelman, David] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel. [Harries, Daniel] Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel. [Harries, Daniel] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel. [Podgornik, Rudi] Univ Ljubljana, J Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. [Podgornik, Rudi] Univ Ljubljana, Fac Math & Phys, Dept Phys, Ljubljana 1000, Slovenia. [Podgornik, Rudi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, NIH, Bethesda, MD 20814 USA. RP Andelman, D (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-69978 Tel Aviv, Israel. EM andelman@post.tau.ae.il RI Andelman, David/C-5557-2012; Podgornik, Rudolf/C-6209-2008; Harries, Daniel/F-7016-2012 OI Andelman, David/0000-0003-3185-8475; Podgornik, Rudolf/0000-0002-3855-4637; Harries, Daniel/0000-0002-3057-9485 FU Israel Science Foundation (ISF) [231/08]; U.S.-Israel Binational Foundation [2006/055]; Israeli and Slovenian Ministries of Science; Slovenian-Israeli research grant; Minerva foundation, Munich, Germany; NIH; National Institute of Child Health and Human Development FX We thank Ariel Abrashkin, Adrian Parsegian and Yoav Tsori for numerous discussions. We are indebted to Don Rau and Brian Todd for helpful discussions and for sharing experimental data with us. D.A. acknowledges support from the Israel Science Foundation (ISF) under Grant No. 231/08 and the U.S.-Israel Binational Foundation (BSF) under Grant No. 2006/055. R.P. and D.H. would like to acknowledge the support from the Israeli and Slovenian Ministries of Science through ajoint Slovenian-Israeli research grant. The Fritz Haber research center is supported by the Minerva foundation, Munich, Germany. This study was in part supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 37 TC 38 Z9 38 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 30 PY 2009 VL 113 IS 17 BP 6001 EP 6011 DI 10.1021/jp9003533 PG 11 WC Chemistry, Physical SC Chemistry GA 438BC UT WOS:000265529900042 PM 19338312 ER PT J AU Kitahata, MM Gange, SJ Abraham, AG Merriman, B Saag, MS Justice, AC Hogg, RS Deeks, SG Eron, JJ Brooks, JT Rourke, SB Gill, MJ Bosch, RJ Martin, JN Klein, MB Jacobson, LP Rodriguez, B Sterling, TR Kirk, GD Napravnik, S Rachlis, AR Calzavara, LM Horberg, MA Silverberg, MJ Gebo, KA Goedert, JJ Benson, CA Collier, AC Van Rompaey, SE Crane, HM McKaig, RG Lau, B Freeman, AM Moore, RD AF Kitahata, Mari M. Gange, Stephen J. Abraham, Alison G. Merriman, Barry Saag, Michael S. Justice, Amy C. Hogg, Robert S. Deeks, Steven G. Eron, Joseph J. Brooks, John T. Rourke, Sean B. Gill, M. John Bosch, Ronald J. Martin, Jeffrey N. Klein, Marina B. Jacobson, Lisa P. Rodriguez, Benigno Sterling, Timothy R. Kirk, Gregory D. Napravnik, Sonia Rachlis, Anita R. Calzavara, Liviana M. Horberg, Michael A. Silverberg, Michael J. Gebo, Kelly A. Goedert, James J. Benson, Constance A. Collier, Ann C. Van Rompaey, Stephen E. Crane, Heidi M. McKaig, Rosemary G. Lau, Bryan Freeman, Aimee M. Moore, Richard D. CA NA-ACCORD Investigators TI Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CD4 CELL COUNT; HUMAN-IMMUNODEFICIENCY-VIRUS; COLLABORATIVE ANALYSIS; DISEASE PROGRESSION; INFECTED PATIENTS; VIRAL LOAD; BASE-LINE; VIROLOGICAL SUPPRESSION; HIV-1-INFECTED PATIENTS; NAIVE INDIVIDUALS AB BACKGROUND The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain. METHODS We conducted two parallel analyses involving a total of 17,517 asymptomatic patients with HIV infection in the United States and Canada who received medical care during the period from 1996 through 2005. None of the patients had undergone previous antiretroviral therapy. In each group, we stratified the patients according to the CD4+ count (351 to 500 cells per cubic millimeter or >500 cells per cubic millimeter) at the initiation of antiretroviral therapy. In each group, we compared the relative risk of death for patients who initiated therapy when the CD4+ count was above each of the two thresholds of interest (early-therapy group) with that of patients who deferred therapy until the CD4+ count fell below these thresholds (deferred-therapy group). RESULTS In the first analysis, which involved 8362 patients, 2084 (25%) initiated therapy at a CD4+ count of 351 to 500 cells per cubic millimeter, and 6278 (75%) deferred therapy. After adjustment for calendar year, cohort of patients, and demographic and clinical characteristics, among patients in the deferred-therapy group there was an increase in the risk of death of 69%, as compared with that in the early-therapy group (relative risk in the deferred-therapy group, 1.69; 95% confidence interval [CI], 1.26 to 2.26; P<0.001). In the second analysis involving 9155 patients, 2220 (24%) initiated therapy at a CD4+ count of more than 500 cells per cubic millimeter and 6935 (76%) deferred therapy. Among patients in the deferred-therapy group, there was an increase in the risk of death of 94% (relative risk, 1.94; 95% CI, 1.37 to 2.79; P<0.001). CONCLUSIONS The early initiation of antiretroviral therapy before the CD4+ count fell below two prespecified thresholds significantly improved survival, as compared with deferred therapy. C1 [Kitahata, Mari M.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Gange, Stephen J.; Abraham, Alison G.; Merriman, Barry; Jacobson, Lisa P.; Kirk, Gregory D.; Gebo, Kelly A.; Lau, Bryan; Freeman, Aimee M.; Moore, Richard D.] Johns Hopkins Univ, Baltimore, MD USA. [Saag, Michael S.] Univ Alabama, Birmingham, AL USA. [Justice, Amy C.] Yale Univ, New Haven, CT USA. [Justice, Amy C.] Vet Affairs Connecticut Healthcare Syst, New Haven, CT USA. [Hogg, Robert S.] British Columbia Ctr Excellence & HIV AIDS, Vancouver, BC, Canada. [Hogg, Robert S.] Simon Fraser Univ, Vancouver, BC, Canada. [Deeks, Steven G.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eron, Joseph J.; Napravnik, Sonia] Univ N Carolina, Chapel Hill, NC USA. [Brooks, John T.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Rourke, Sean B.; Rachlis, Anita R.; Calzavara, Liviana M.] Univ Toronto, Toronto, ON, Canada. [Gill, M. John] Univ Calgary, Calgary, AB, Canada. [Bosch, Ronald J.] Harvard Univ, Sch Med, Boston, MA USA. [Klein, Marina B.] McGill Univ, Montreal, PQ, Canada. [Rodriguez, Benigno] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Sterling, Timothy R.] Vanderbilt Univ, Nashville, TN USA. [Horberg, Michael A.; Silverberg, Michael J.] Kaiser Permanente No Calif, Oakland, CA USA. [Goedert, James J.; McKaig, Rosemary G.] NIH, Bethesda, MD 20892 USA. [Benson, Constance A.] Univ Calif San Diego, San Diego, CA 92103 USA. RP Kitahata, MM (reprint author), Univ Washington, Harborview Med Ctr, 325 9th Ave,Box 359931, Seattle, WA 98104 USA. EM kitahata@u.washington.edu RI Hogg, Robert/B-2783-2012; Rodriguez, Benigno/C-3365-2009; Gill, John/G-7083-2016; OI Rodriguez, Benigno/0000-0001-9736-7957; Gill, John/0000-0002-8546-8790; Gange, Stephen/0000-0001-7842-512X; Hogg, Robert/0000-0003-3463-5488 FU National Institutes of Health; Agency for Healthcare Research and Quality FX Supported by grants from the National Institutes of Health and from the Agency for Healthcare Research and Quality. NR 63 TC 636 Z9 670 U1 4 U2 34 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 30 PY 2009 VL 360 IS 18 BP 1815 EP 1826 DI 10.1056/NEJMoa0807252 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 438MU UT WOS:000265560300004 PM 19339714 ER PT J AU Hoofnagle, JH AF Hoofnagle, Jay H. TI A Step Forward in Therapy for Hepatitis C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PEGINTERFERON ALPHA-2A; RIBAVIRIN; VX-950; INTERFERON-ALPHA-2B; COMBINATION; TELAPREVIR; GENOTYPE-1; INHIBITOR C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. NR 14 TC 36 Z9 37 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 30 PY 2009 VL 360 IS 18 BP 1899 EP 1901 DI 10.1056/NEJMe0901869 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 438MU UT WOS:000265560300014 PM 19403908 ER PT J AU Webb, SJ Sparks, BF Friedman, SD Shaw, DWW Giedd, J Dawson, G Dager, SR AF Webb, Sara Jane Sparks, Bobbi-Faun Friedman, Seth D. Shaw, Dennis W. W. Giedd, Jay Dawson, Geraldine Dager, Stephen R. TI Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Cerebellum; MRI; Vermis; Developmental delay ID POSTERIOR-FOSSA STRUCTURES; INFANTILE-AUTISM; YOUNG-CHILDREN; WILLIAMS-SYNDROME; FRONTAL-LOBE; BRAIN; MRI; ABNORMALITIES; GRAY; NEUROPATHOLOGY AB Cerebellar histopathological abnormalities have been well documented in autism, although findings of structural differences, as determined by magnetic resonance imaging, have been less consistent. This report explores specific cerebellar vermal structures and their relation with severity of symptoms and cognitive functioning in young children with autism spectrum disorder (ASD). Children with ASD aged 3 to 4 years were compared with typically developing children (TD) matched to the ASD children on chronological age, and children with developmental delay (DD) matched to the ASD children on both chronological and mental age. Volumes of the cerebellum and midsagittal vermal areas were measured from 3-D T1-weighted magnetic resonance images. Children with ASD had reduced total vermis volumes compared with children with TD after controlling for age, sex, and overall cerebral volume or cerebellum volume. In particular, the vermis lobe VI-VII area was reduced in children ASD compared with TD children. Children with DD had smaller total vermis areas compared with children with ASD and TD. Within the ASD group, cerebellar measurements were not correlated with symptom severity, or verbal, non-verbal or full scale IQ. Within the DD group, larger cerebellar measurements were correlated with fewer impairments. The specific relation between altered cerebellar structure and symptom expression in autism remains unclear. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Webb, Sara Jane; Dawson, Geraldine] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Webb, Sara Jane; Dawson, Geraldine] Univ Washington, Ctr Human Dev & Disabil, Seattle, WA 98195 USA. [Sparks, Bobbi-Faun; Friedman, Seth D.; Shaw, Dennis W. W.; Dager, Stephen R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Shaw, Dennis W. W.] Seattle Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Giedd, Jay] NIMH, Bethesda, MD 20892 USA. [Dawson, Geraldine] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Webb, SJ (reprint author), Box 357920 CHDD, Seattle, WA 98195 USA. EM sjwebb@u.washington.edu RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU National Institute of Child Health and Human Development [U19HD34565, P50HD066782, R01HD55741]; National Institute of Mental Health [U54MH066399]; Autism Speaks FX This study was funded by grants from the National Institute of Child Health and Human Development (U19HD34565, P50HD066782, and R01HD-55741) and the National Institute of Mental Health (U54MH066399); writing of this manuscript was supported, as well, by a grant from Autism Speaks. NR 45 TC 59 Z9 65 U1 4 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2009 VL 172 IS 1 BP 61 EP 67 DI 10.1016/j.pscychresns.2008.06.001 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 434AI UT WOS:000265247200010 PM 19243924 ER PT J AU Vythilingam, M Nelson, EE Scaramozza, M Waldeck, T Hazlett, G Southwick, SM Pine, DS Drevets, W Charney, DS Ernst, M AF Vythilingam, Meena Nelson, Eric E. Scaramozza, Matthew Waldeck, Tracy Hazlett, Gary Southwick, Steven M. Pine, Daniel S. Drevets, Wayne Charney, Dennis S. Ernst, Monique TI Reward circuitry in resilience to severe trauma: An fMRI investigation of resilient special forces soldiers SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Reward; Resilience; Trauma; Posttraumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; NEURAL RESPONSES; VISUALIZATION; VOLUMES AB Enhanced brain reward function could contribute to resilience to trauma. Reward circuitry in active duty, resilient special forces (SF) soldiers was evaluated using functional magnetic resonance imaging during a monetary incentive delay task. Findings in this group of resilient individuals revealed unique patterns of activation during expectation of reward in the subgenual prefrontal cortex and nucleus accumbens area, regions pivotal to reward processes. Published by Elsevier Ireland Ltd. C1 [Vythilingam, Meena; Nelson, Eric E.; Scaramozza, Matthew; Waldeck, Tracy; Pine, Daniel S.; Drevets, Wayne; Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Hazlett, Gary] John F Kennedy Special Warfare Training & Sch, Psychol Applicat Directorate, Ft Bragg, NC USA. [Southwick, Steven M.] Yale Univ, Sch Med, New Haven, CT USA. [Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA. RP Vythilingam, M (reprint author), 15 K N Dr,Rm 111,MSC 2670, Bethesda, MD 20892 USA. EM meena.vythi@nih.gov RI Nelson, Eric/B-8980-2008 OI Nelson, Eric/0000-0002-3376-2453 FU National Institutes of Health; National Institute of Mental Health FX The authors acknowledge Kayleen Hadd, M.S.N. and Rajni Agarwal, M.A., for help with subject evaluations, Brian Pardoe (BP) and Mark Hickey (MH) for help with recruitment of the special force soldiers and C. Andrew Morgan III, M.D. for facilitating the study. This research was supported by the Intramural Program of the National Institutes of Health, National Institute of Mental Health. NR 17 TC 28 Z9 32 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 30 PY 2009 VL 172 IS 1 BP 75 EP 77 DI 10.1016/j.pscychresns.2008.06.008 PG 3 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 434AI UT WOS:000265247200012 PM 19243926 ER PT J AU Eddins, D Klein, RC Yakel, JL Levin, ED AF Eddins, Donnie Klein, Rebecca C. Yakel, Jerrel L. Levin, Edward D. TI Hippocampal infusions of apolipoprotein E peptides induce long-lasting cognitive impairment SO BRAIN RESEARCH BULLETIN LA English DT Article DE Alzheimer's disease; Learning; Memory; Radial-arm maze; Hippocampus; ApoE4 ID NICOTINIC ACETYLCHOLINE-RECEPTORS; THROMBIN-CLEAVAGE FRAGMENT; E-DERIVED PEPTIDES; ALZHEIMERS-DISEASE; APOE GENOTYPE; ALLELE; NEUROTOXICITY; DEFICITS; NEURONS; RISK AB The inheritance of the epsilon 4 allele of apolipoprotein E (ApoE4) and cholinergic system dysfunction have long been associated with the pathology of Alzheimer's disease (AD). Recently, in vitro studies have established a direct link between ApoE and cholinergic function in that synthetic peptides containing segments of the ApoE protein (ApoE(133-149) and ApoE(141-148)) interact with alpha 7 nicotinic acetylcholine receptors (nAChRs) in the hippocampus. This raises the possibility that ApoE peptides may contribute to cognitive impairment in AD in that the hippocampus plays a key role in cognitive functioning. To test this, we acutely infused ApoE peptides into the ventral hippocampus of female Sprague-Dawley rats and assessed the resultant effects on radial-arm maze choice accuracy over a period of weeks after the infusion. Local ventral hippocampal infusion of ApoE peptides caused significant cognitive impairment in radial-arm maze learning that persisted several weeks after the acute infusion. This persisting deficit may be an important model for understanding the relationship between ApoE protein-induced neurotoxicity and cognitive impairment as well as serve as a platform for the development of new therapies to avoid neurotoxicity and cognitive decline. (c) 2009 Published by Elsevier Inc. C1 [Eddins, Donnie; Levin, Edward D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Klein, Rebecca C.; Yakel, Jerrel L.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Levin, ED (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3412, Durham, NC 27710 USA. EM edlevin@duke.edu FU Merck & Co. Inc./United Negro College Fund (UNCF/Merck) Science Initiative; NIEHS; NIH FX Research support was provided in part by the Merck & Co. Inc./United Negro College Fund (UNCF/Merck) Science Initiative and NIEHS. We thank the Intramural Research Program of the NIEHS, NIH. NR 22 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR 29 PY 2009 VL 79 IS 2 BP 111 EP 115 DI 10.1016/j.brainresbull.2009.01.003 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 435IX UT WOS:000265338700004 PM 19185602 ER PT J AU Francesconi, W Berton, F Repunte-Canonigo, V Hagihara, K Thurbon, D Lekic, D Specio, SE Greenwell, TN Chen, SA Rice, KC Richardson, HN O'Dell, LE Zorrilla, EP Morales, M Koob, GF Sanna, PP AF Francesconi, Walter Berton, Fulvia Repunte-Canonigo, Vez Hagihara, Kazuki Thurbon, David Lekic, Dusan Specio, Sheila E. Greenwell, Thomas N. Chen, Scott A. Rice, Kenner C. Richardson, Heather N. O'Dell, Laura E. Zorrilla, Eric P. Morales, Marisela Koob, George F. Sanna, Pietro Paolo TI Protracted Withdrawal from Alcohol and Drugs of Abuse Impairs Long-Term Potentiation of Intrinsic Excitability in the Juxtacapsular Bed Nucleus of the Stria Terminalis SO JOURNAL OF NEUROSCIENCE LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; INACTIVATING POTASSIUM CURRENT; NEOCORTICAL PYRAMIDAL NEURONS; STRESS-INDUCED REINSTATEMENT; CENTRAL EXTENDED AMYGDALA; COCAINE-SEEKING BEHAVIOR; CRF1 RECEPTOR ANTAGONIST; CHRONIC ETHANOL EXPOSURE; ANXIETY-LIKE BEHAVIOR; IN-VIVO AB The juxtacapsular bed nucleus of the stria terminalis (jcBNST) is activated in response to basolateral amygdala (BLA) inputs through the stria terminalis and projects back to the anterior BLA and to the central nucleus of the amygdala. Here we show a form of long-term potentiation of the intrinsic excitability (LTP-IE) of jcBNST neurons in response to high-frequency stimulation of the stria terminalis. This LTP-IE, which was characterized by a decrease in the firing threshold and increased temporal fidelity of firing, was impaired during protracted withdrawal from self-administration of alcohol, cocaine, and heroin. Such impairment was graded and was more pronounced in rats that self-administered amounts of the drugs sufficient to maintain dependence. Dysregulation of the corticotropin-releasing factor (CRF) system has been implicated in manifestation of protracted withdrawal from dependent drug use. Administration of the selective corticotropin-releasing factor receptor 1 (CRF(1)) antagonist R121919 [2,5-dimethyl-3-(6-dimethyl-4-methylpyridin-3-yl)-7-dipropylamino-pyrazolo[1,5-a]pyrimidine)], but not of the CRF(2) antagonist astressin(2)-B, normalized jcBNST LTP-IE in animals with a history of alcohol dependence; repeated, but not acute, administration of CRF itself produced a decreased jcBNST LTP-IE. Thus, changes in the intrinsic properties of jcBNST neurons mediated by chronic activation of the CRF system may contribute to the persistent emotional dysregulation associated with protracted withdrawal. C1 [Francesconi, Walter; Berton, Fulvia; Repunte-Canonigo, Vez; Hagihara, Kazuki; Thurbon, David; Lekic, Dusan; Sanna, Pietro Paolo] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Specio, Sheila E.; Greenwell, Thomas N.; Chen, Scott A.; Richardson, Heather N.; O'Dell, Laura E.; Zorrilla, Eric P.; Koob, George F.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, NIH, Bethesda, MD 20892 USA. [Morales, Marisela] Natl Inst Drug Abuse, Lab Cellular Neurophysiol, NIH, Baltimore, MD 21224 USA. [Francesconi, Walter] Univ Pisa, Dept Biol, I-56126 Pisa, Italy. RP Francesconi, W (reprint author), Scripps Res Inst, Mol & Integrat Neurosci Dept, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM wfranc@scripps.edu; psanna@scripps.edu RI koob, george/P-8791-2016; OI Greenwell, Thomas/0000-0001-6069-0064; Richardson, Heather/0000-0001-7659-1212 FU National Institutes of Health [AA016587, DA013821, AA013191, AA008459, DA004043, DA004398, AA006420]; Pearson Center for Alcoholism and Addiction Research; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by National Institutes of Health Grants AA016587 (W.F.), DA013821, AA013191 (P.P.S.), AA008459, DA004043, DA004398, and AA006420 (G.F.K.) and by the Pearson Center for Alcoholism and Addiction Research. A portion of this work was supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. We thank Drs. Floyd Bloom and Paul Kenny of The Scripps Research Institute, Elisabeth Walcott of the Neuroscience Institute, and Sascha du Lac of The Salk Institute for critical review of this manuscript, Drs. Bert Weiss and Tamas Bartfai of The Scripps Research Institute and Attila Szucs of the Institute for Nonlinear Science (University of California, San Diego) for discussion, and Dr. Caroline M. Lanigan for review of statistical analyses, Lena van der Stap for assistance with the analysis of microarray data, and Mike Arends for editorial assistance. NR 111 TC 45 Z9 45 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 29 PY 2009 VL 29 IS 17 BP 5389 EP 5401 DI 10.1523/JNEUROSCI.5129-08.2009 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 439QL UT WOS:000265642000005 PM 19403807 ER PT J AU Messinger, A Lebedev, MA Kralik, JD Wise, SP AF Messinger, Adam Lebedev, Mikhail A. Kralik, Jerald D. Wise, Steven P. TI Multitasking of Attention and Memory Functions in the Primate Prefrontal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID DELAY-PERIOD ACTIVITY; SPATIAL WORKING-MEMORY; NEURONAL-ACTIVITY; TEMPORAL CORTEX; PREMOTOR CORTEX; RHESUS-MONKEY; VISUAL AREA; SACCADE DIRECTION; TARGET SELECTION; MACAQUE MONKEY AB In motor and sensory areas of cortex, neuronal activity often depends on the location of a movement target or a sensory stimulus, with each neuron tuned to a single part of space called a preferred direction (when motor) or a receptive field (when sensory). As we previously reported, some neurons in the monkey prefrontal cortex are tuned to two parts of space, which we interpreted as reflecting attention and working memory, respectively. Monkeys performed a behavioral task in which they attended to a visual stimulus at one location while remembering a second place, and these locations were varied from trial to trial to assess spatial tuning. Most spatially tuned neurons specialized in either attentional or mnemonic processing, but about one-third of the cells showed tuning for both. Here, we show that the latter population, called multitasking neurons, improves the encoding of both the attended and remembered locations. These neurons do so for three reasons: (1) the preferred directions for attention and for working memory usually differ (and often diametrically oppose one another), (2) they have stronger tuning than specialized cells, and (3) pairs of multitasking neurons represent these cognitive parameters more efficiently than pairs that include even a single specialized cell. These findings suggest that multitasking neurons provide a computational advantage for behaviors that place simultaneous demands on two or more cognitive processes. C1 [Messinger, Adam; Lebedev, Mikhail A.; Kralik, Jerald D.; Wise, Steven P.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Messinger, A (reprint author), NIMH, Lab Brain & Cognit, 49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA. EM messinga@mail.nih.gov RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 FU National Institute of Mental Health Division of Intramural Research [Z01MH-01092] FX This work was supported by National Institute of Mental Health Division of Intramural Research Grant Z01MH-01092. We thank Dr. Andrew R. Mitz for engineering support, Jim Fellows for assistance in behavioral training, Daniel Muldrew for assistance with the data analysis, and Alex Cummings for preparing the histological material. NR 48 TC 16 Z9 16 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 29 PY 2009 VL 29 IS 17 BP 5640 EP 5653 DI 10.1523/JNEUROSCI.3857-08.2009 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 439QL UT WOS:000265642000028 PM 19403830 ER PT J AU Chow, L Rezmann, L Catt, KJ Louis, WJ Frauman, AG Nahmias, C Louis, SNS AF Chow, L. Rezmann, L. Catt, K. J. Louis, W. J. Frauman, A. G. Nahmias, C. Louis, S. N. S. TI Role of the renin-angiotensin system in prostate cancer SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE Renin-angiotensin system; Angiotensin II; Prostate cancer ID II TYPE-1 RECEPTOR; GENE INSERTION/DELETION POLYMORPHISM; CONVERTING ENZYME-INHIBITION; ENDOTHELIAL GROWTH-FACTOR; HUMAN FALLOPIAN-TUBE; SMOOTH-MUSCLE-CELLS; TYROSINE KINASES; EPITHELIAL-CELLS; CARCINOMA-CELLS; RAT PROSTATE AB Prostate cancer is highly prevalent in Western society, and its early stages can be controlled by androgen ablation therapy. However, the cancer eventually regresses to an androgen-independent state for which there is no effective treatment. The renin-angiotensin system (RAS), in particular the octapeptide angiotensin 11, is now recognised to have important effects on growth factor signalling and cell growth in addition to its well known actions on blood pressure, fluid homeostasis and electrolyte balance. All components of the RAS have been recently identified in the prostate, consistent with the expression of it local RAS system in this tissue. This review focuses on the role of the RAS in the prostate, and the possibility that this pathway may be a potential therapeutic target for the treatment of prostate cancer and other prostatic diseases. (C) 2008 Elsevier Ireland Ltd. All rights reserved C1 [Chow, L.; Rezmann, L.; Louis, W. J.; Frauman, A. G.; Louis, S. N. S.] Univ Melbourne, Dept Med, Clin Pharmacol & Therapeut Unit, Austin Hlth, Heidelberg, Vic 3084, Australia. [Catt, K. J.; Louis, S. N. S.] NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. [Nahmias, C.; Louis, S. N. S.] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, F-75014 Paris, France. RP Louis, SNS (reprint author), Univ Melbourne, Dept Med, Clin Pharmacol & Therapeut Unit, Austin Hlth, Studley Rd,Level 5,Lance Townsend Bldg, Heidelberg, Vic 3084, Australia. EM simonnsl@unimelb.edu.au FU INSERM/NHMRC; Sir Edward Dunlop Medical Research Foundation; Austin Hospital Medical Research Foundation; University of Melbourne FX This work has been kindly supported by the INSERM/NH&MRC, Sir Edward Dunlop Medical Research Foundation, the Austin Hospital Medical Research Foundation and the University of Melbourne. NR 151 TC 17 Z9 18 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD APR 29 PY 2009 VL 302 IS 2 SI SI BP 219 EP 229 DI 10.1016/j.mce.2008.08.032 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 436YE UT WOS:000265451200014 PM 18824067 ER PT J AU Guo, J Jou, W Gavrilova, O Hall, KD AF Guo, Juen Jou, William Gavrilova, Oksana Hall, Kevin D. TI Persistent Diet-Induced Obesity in Male C57BL/6 Mice Resulting from Temporary Obesigenic Diets SO PLOS ONE LA English DT Article AB Background: Does diet-induced obesity persist after an obesigenic diet is removed? We investigated this question by providing male C57BL/6 mice with free access to two different obesigenic diets followed by a switch to chow to determine if obesity was reversible. Methodology/Principal Findings: Male C57BL/6 mice were randomly assigned to five weight-matched groups: 1) C group that continuously received a chow diet; 2) HF group on a 60% high fat diet; 3) EN group on the high fat diet plus liquid Ensure (R); 4) HF-C group switched from high fat to chow after 7 weeks; 5) EN-C group switched from high fat plus Ensure (R) to chow after 7 weeks. All food intake was ad libitum. Body weight was increased after 7 weeks on both obesigenic diets (44.6 +/- 0.65, 39.8 +/- 0.63, and 28.6 +/- 0.63 g for EN, HF, and C groups, respectively) and resulted in elevated concentrations of serum insulin, glucose, and leptin and lower serum triglycerides. Development of obesity in HF and EN mice was caused by increased energy intake and a relative decrease of average energy output along with decreased ambulatory activity. After the switch to chow, the HF-C and EN-C groups lost weight but subsequently maintained a state of persistent obesity in comparison to the C group (34.8 +/- 1.2, 34.1 +/- 1.2 vs. 30.8 +/- 0.8 g respectively; P < 0.05) with a 40-50% increase of body fat. All serum hormones and metabolites returned to control levels with the exception of a trend for increased leptin. The HF-C and EN-C groups had an average energy output in line with the C group and the persistent obesity was maintained despite a non-significant increase of energy intake of less than 1 kcal/d at the end of the study. Conclusion: Our results illustrate the importance of considering the history of energy imbalance in determining body weight and that a persistent elevation of body weight after removal of obesigenic diets can result from very small increases of energy intake. RP Guo, J (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU Intramural NIH HHS NR 37 TC 39 Z9 39 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2009 VL 4 IS 4 AR e5370 DI 10.1371/journal.pone.0005370 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 439BG UT WOS:000265601100012 PM 19401758 ER PT J AU Ambros, PF Ambros, IM Brodeur, GM Haber, M Khan, J Nakagawara, A Schleiermacher, G Speleman, F Spitz, R London, WB Cohn, SL Pearson, ADJ Maris, JM AF Ambros, P. F. Ambros, I. M. Brodeur, G. M. Haber, M. Khan, J. Nakagawara, A. Schleiermacher, G. Speleman, F. Spitz, R. London, W. B. Cohn, S. L. Pearson, A. D. J. Maris, J. M. TI International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee SO BRITISH JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Industrial-and-Organizational-Psychology CY APR 27-29, 2007 CL New York, NY SP Soc Ind & Org Psychol DE neuroblastoma; treatment planning; genomic; translational; international consensus; INRG; genetic risk factors ID PEDIATRIC-ONCOLOGY-GROUP; CHROMOSOME ARM 17Q; DEAD BOX GENE; BONE-MARROW; N-MYC; PROGNOSTIC-SIGNIFICANCE; NEURO-BLASTOMA; SCHWANN-CELLS; ALLELIC LOSS; TUMOR-CELLS AB Neuroblastoma serves as a paradigm for utilising tumour genomic data for determining patient prognosis and treatment allocation. However, before the establishment of the International Neuroblastoma Risk Group (INRG) Task Force in 2004, international consensus on markers, methodology, and data interpretation did not exist, compromising the reliability of decisive genetic markers and inhibiting translational research efforts. The objectives of the INRG Biology Committee were to identify highly prognostic genetic aberrations to be included in the new INRG risk classification schema and to develop precise definitions, decisive biomarkers, and technique standardisation. The review of the INRG database (n = 8800 patients) by the INRG Task Force finally enabled the identification of the most significant neuroblastoma biomarkers. In addition, the Biology Committee compared the standard operating procedures of different cooperative groups to arrive at international consensus for methodology, nomenclature, and future directions. Consensus was reached to include MYCN status, 11q23 allelic status, and ploidy in the INRG classification system on the basis of an evidence-based review of the INRG database. Standardised operating procedures for analysing these genetic factors were adopted, and criteria for proper nomenclature were developed. Neuroblastoma treatment planning is highly dependant on tumour cell genomic features, and it is likely that a comprehensive panel of DNA-based biomarkers will be used in future risk assignment algorithms applying genome-wide techniques. Consensus on methodology and interpretation is essential for uniform INRG classification and will greatly facilitate international and cooperative clinical and translational research studies. C1 [Ambros, P. F.; Ambros, I. M.] CCRI, A-1090 Vienna, Austria. [Brodeur, G. M.; Maris, J. M.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Haber, M.] Childrens Canc Inst Australia, Sydney, NSW, Australia. [Khan, J.] NCI, Bethesda, MD 20892 USA. [Nakagawara, A.] Chiba Canc Ctr, Res Inst, Chiba, Japan. [Schleiermacher, G.] Inst Curie, Paris, France. [Speleman, F.] Ctr Med Genet, Ghent, Belgium. [Spitz, R.] Univ Cologne, D-5000 Cologne 41, Germany. [London, W. B.] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL USA. [Cohn, S. L.] Univ Chicago, Chicago, IL 60637 USA. [Pearson, A. D. J.] Inst Canc Res, Paediat Sect, Surrey, England. [Pearson, A. D. J.] Royal Marsden Hosp, Surrey, England. RP Ambros, PF (reprint author), CCRI, Kinderspitalgasse 6, A-1090 Vienna, Austria. EM ambros@ccri.at; maris@chop.edu RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Ambros, Peter F./0000-0002-5507-7211; Cohn, Susan/0000-0001-5749-7650 FU Cancer Research UK NR 57 TC 116 Z9 127 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD APR 28 PY 2009 VL 100 IS 9 BP 1471 EP 1482 DI 10.1038/sj.bjc.6605014 PG 12 WC Oncology SC Oncology GA 438SH UT WOS:000265575200015 PM 19401703 ER PT J AU Brock, KE Gridley, G Chiu, BCH Ershow, AG Lynch, CF Cantor, KP AF Brock, Kaye E. Gridley, Gloria Chiu, Brian C. -H. Ershow, Abby G. Lynch, Charles F. Cantor, Kenneth P. TI Dietary fat and risk of renal cell carcinoma in the USA: a case-control study SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Kidney cancer; Renal cell carcinoma; Case-control studies; Dietary fat ID UNITED-STATES; POSTMENOPAUSAL WOMEN; LIPID-PEROXIDATION; DIABETES-MELLITUS; KIDNEY CANCER; HYPERTENSION; POPULATION; OBESITY; EPIDEMIOLOGY; IOWA AB An increased risk of renal cell carcinoma (RCC) has been linked with obesity. However, there is limited information about the contribution of dietary fat and fat-related food groups to RCC risk. A population-based case-control study of 406 cases and 2434 controls aged 40-85 years was conducted in Iowa (1986-89). For 323 cases and 1820 controls from the present study, information on dietary intake from foods high in fat nutrients and other lifestyle factors was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, physical activity, alcohol and vegetable intake and tea and coffee consumption. In all nutrient analyses, energy density estimates were used. Dietary nutrient intake of animal fat, saturated fat, oleic acid and cholesterol was associated with an elevated risk of RCC (OR = 1.9, 95 % CI 1.3, 2.9, P(trend) < 0.001; OR = 2.6, 95 % CI 1.6, 4.0, P(trend) < 0.001; OR = 1.9, 95 % CI 1.2, 2.9, P(trend) = 0.01; OR = 1.9, 95 % CI 1.3, 2.8, P(trend) = 0.006, respectively, for the top quartile compared with the bottom quartile of intake). Increased risks were also associated with high-fat spreads, red and cured meats and dairy products (OR = 2.0, 95 % CI 1.4, 3.0, P(trend) = 0.001; OR = 1.7, 95 % CI 1.0, 2.2, P(trend) = 0.01; OR = 1.8, 95 % CI 1.2, 2.7, P(trend) = 0.02; OR = 1.6, 95 % CI 1.1, 2.3, P(trend) = 0.02, respectively). In both the food groups and nutrients, there was a significant dose-response with increased intake. Our data also indicated that the association of RCC with high-fat spreads may be stronger among individuals with hypertension. These findings deserve further investigation in prospective studies. C1 [Brock, Kaye E.] Univ Sydney, Fac Heath Sci, Dept Behav & Community Hlth Sci, Sydney, NSW 2006, Australia. [Gridley, Gloria; Cantor, Kenneth P.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Chiu, Brian C. -H.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. [Ershow, Abby G.] NHLBI, US Dept HHS, NIH, Bethesda, MD 20892 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. RP Brock, KE (reprint author), Univ Sydney, Fac Heath Sci, Dept Behav & Community Hlth Sci, Sydney, NSW 2006, Australia. EM k.brock@usyd.edu.au FU National Institutes of Health (NIH); NCI; Division of Cancer Epidemiology and Genetics (DCEG); Sydney University; NSW; Australia Sabbatical Program FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), NCI, Division of Cancer Epidemiology and Genetics (DCEG), and Sydney University, NSW, Australia Sabbatical Program for K. E. B. In addition, we acknowledge the invaluable support of Mr David Check, research assistant, Biostatistics Branch, DCEG, NCI, NIH. Contributions of the co-authors were as follows: K. P. C. designed the study and had overall responsibility for the project; A. G. C. designed the collection of dietary information; C. F. L. was responsible for overseeing data collection; G. G., K. E. B. and B. C.-H. C. conducted the data analysis; K. E. B. drafted the paper and all authors contributed to the final completion of the manuscript. None of the authors have any conflicts of interest (personal, commercial, political, academic or financial). NR 52 TC 14 Z9 15 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD APR 28 PY 2009 VL 101 IS 8 BP 1228 EP 1238 DI 10.1017/S0007114508056043 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 440KH UT WOS:000265698700015 PM 18786276 ER PT J AU Cimato, T Beers, J Ding, SL Ma, MC McCoy, JP Boehm, M Nabel, EG AF Cimato, Thomas Beers, Jeanette Ding, Shunli Ma, Mingchao McCoy, J. Phillip Boehm, Manfred Nabel, Elizabeth G. TI Neuropilin-1 Identifies Endothelial Precursors in Human and Murine Embryonic Stem Cells Before CD34 Expression SO CIRCULATION LA English DT Article DE endothelium; stem cells; vascular biology; vasculogenesis ID DIFFERENTIATION; ANGIOGENESIS; PROGENITORS; VEGF; HEMANGIOBLAST; PROGRESSION; INDUCTION; MESODERM; GROWTH; GENES AB Background-In murine embryonic stem cells, the onset of vascular endothelial growth factor receptor 2 (VEGFR-2) expression identifies endothelial precursors. Undifferentiated human embryonic stem cells express VEGFR-2, and VEGFR-2 expression persists on differentiation. The objective of our study was to identify a single population of endothelial precursors with common identifying features from both human and murine embryonic stem cells. Methods and Results-We report that expression of the VEGF coreceptor neuropilin-1 (NRP-1) coincides with expression of Brachyury and VEGFR-2 and identifies endothelial precursors in murine and human embryonic stem cells before CD31 or CD34 expression. When sorted and differentiated, VEGFR-2(+)NRP-1(+) cells form endothelial-like colonies that express CD31 and CD34 7-fold more efficiently than NRP-1 cells. Finally, antagonism of both the VEGF and Semaphorin binding functions of NRP-1 impairs the differentiation of vascular precursors to endothelial cells. Conclusions-The onset of NRP-1 expression identifies endothelial precursors in murine and human stem cells. The findings define the origin of a single population of endothelial precursors from human and murine stem cells to endothelial cells. Additionally, the function of both the VEGF and Semaphorin binding activities of NRP-1 has important roles in the differentiation of stem cells to endothelial cells, providing novel insights into the role of NRP-1 in a model of vasculogenesis. (Circulation. 2009;119:2170-2178.) C1 [Nabel, Elizabeth G.] NHGRI, Vasc Biol & Genom Sect, Bethesda, MD 20892 USA. [Cimato, Thomas; Ding, Shunli; Ma, Mingchao; McCoy, J. Phillip; Boehm, Manfred; Nabel, Elizabeth G.] NHLBI, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHGRI, Vasc Biol & Genom Sect, 31 Ctr Dr,Bldg 31 Room 5A48, Bethesda, MD 20892 USA. EM nhlbiiod@mail.nih.gov OI Cimato, Thomas/0000-0001-9230-4463 FU National Human Genome Research Institute; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Heart, Lung, and Blood Institute, and National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 22 TC 18 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 28 PY 2009 VL 119 IS 16 BP 2170 EP U74 DI 10.1161/CIRCULATIONAHA.109.849596 PG 17 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 438UG UT WOS:000265580300008 PM 19364973 ER PT J AU Friedrich, MG Sechtem, U Schulz-Menger, J Holmvang, G Alakija, P Cooper, LT White, JA Abdel-Aty, H Gutberlet, M Prasad, S Aletras, A Laissy, JP Paterson, I Filipchuk, NG Kumar, A Pauschinger, M Liu, P AF Friedrich, Matthias G. Sechtem, Udo Schulz-Menger, Jeanette Holmvang, Godtfred Alakija, Pauline Cooper, Leslie T. White, James A. Abdel-Aty, Hassan Gutberlet, Matthias Prasad, Sanjay Aletras, Anthony Laissy, Jean-Pierre Paterson, Ian Filipchuk, Neil G. Kumar, Andreas Pauschinger, Matthias Liu, Peter CA Int Consensus Grp Cardiovasc Magne TI Cardiovascular Magnetic Resonance in Myocarditis: A JACC White Paper SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE cardiovascular magnetic resonance; myocarditis; consensus ID SUDDEN CARDIAC DEATH; AMERICAN-HEART-ASSOCIATION; ENDOMYOCARDIAL BIOPSY; ECHOCARDIOGRAPHIC FINDINGS; SUSPECTED MYOCARDITIS; DELAYED ENHANCEMENT; VIRAL MYOCARDITIS; GADOLINIUM-DTPA; ENZYME-RELEASE; CHEST-PAIN AB Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., "Lake Louise Criteria"). C1 [Friedrich, Matthias G.; Filipchuk, Neil G.; Kumar, Andreas] Univ Calgary, Stephenson Cardiovasc MR Ctr, Libin Cardiovasc Inst Alberta, Dept Cardiac Sci & Radiol, Calgary, AB T2N 2T9, Canada. [Alakija, Pauline] Univ Calgary, Dept Pathol, Calgary, AB T2N 2T9, Canada. [Sechtem, Udo] Robert Bosch Krankenhaus, Dept Cardiol, Stuttgart, Germany. [Schulz-Menger, Jeanette; Abdel-Aty, Hassan] Charite Univ Med Berlin, HELIOS Klinikum Berlin Buch, Franz Volhard Klin, Berlin, Germany. [Holmvang, Godtfred] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cooper, Leslie T.] Mayo Clin, Coll Med, Rochester, MN USA. [White, James A.] London Hlth Sci Ctr, London, ON, Canada. [Gutberlet, Matthias] Univ Leipzig, Dept Diagnost & Intervent Radiol, Leipzig, Germany. [Prasad, Sanjay] Royal Brompton Hosp, London SW3 6LY, England. [Aletras, Anthony] NHLBI, NIH, Bethesda, MD 20892 USA. [Laissy, Jean-Pierre] Hop Bichat Claude Bernard, Dept Radiol, F-75877 Paris, France. [Paterson, Ian] Univ Alberta, Div Cardiol, Edmonton, AB, Canada. [Pauschinger, Matthias] Klinikum Nurnberg Sud, Dept Cardiol, Nurnberg, Germany. [Liu, Peter] Toronto Gen Hosp, Max Bell Res Ctr, Toronto, ON, Canada. RP Friedrich, MG (reprint author), Univ Calgary, Stephenson Cardiovasc MR Ctr, Libin Cardiovasc Inst Alberta, Dept Cardiac Sci & Radiol, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM matthias.friedrich@ucalgary.ca OI Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z99 HL999999] NR 65 TC 538 Z9 571 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 28 PY 2009 VL 53 IS 17 BP 1475 EP 1487 DI 10.1016/j.jacc.2009.02.007 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 437VN UT WOS:000265515100001 PM 19389557 ER PT J AU Misteli, T AF Misteli, Tom TI Self-organization in the genome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID GENE-EXPRESSION; ARCHITECTURE C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 13 TC 38 Z9 39 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2009 VL 106 IS 17 BP 6885 EP 6886 DI 10.1073/pnas.0902010106 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438VS UT WOS:000265584500002 PM 19416923 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Amplification of signaling via cellular allosteric relay and protein disorder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID ACTIVATOR PROTEIN; BINDING; CAMP; COOPERATIVITY; RESOLUTION; CATALYSIS; MECHANISM; DOMAIN; KINASE C1 [Ma, Buyong; Nussinov, Ruth] NCI, Basic Res Program, Ctr Canc Res Nanobiol Program, SAIC Frederick, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Res Program, Ctr Canc Res Nanobiol Program, SAIC Frederick, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 22 TC 27 Z9 27 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2009 VL 106 IS 17 BP 6887 EP 6888 DI 10.1073/pnas.0903024106 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438VS UT WOS:000265584500003 PM 19416924 ER PT J AU Neuman, KC Charvin, G Bensimon, D Croquette, V AF Neuman, K. C. Charvin, G. Bensimon, D. Croquette, V. TI Mechanisms of chiral discrimination by topoisomerase IV SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA; magnetic tweezers; single molecule; topology; segregation ID POSITIVELY SUPERCOILED DNA; C-TERMINAL DOMAIN; ESCHERICHIA-COLI; SINGLE-MOLECULE; PREFERENTIAL RELAXATION; II TOPOISOMERASES; REPLICATION; UNLINKING; TOPOLOGY; GYRASE AB Topoisomerase IV (Topo IV), an essential ATP-dependent bacterial type II topoisomerase, transports one segment of DNA through a transient double-strand break in a second segment of DNA. In vivo, Topo IV unlinks catenated chromosomes before cell division and relaxes positive supercoils generated during DNA replication. In vitro, Topo IV relaxes positive supercoils at least 20-fold faster than negative supercoils. The mechanisms underlying this chiral discrimination by Topo IV and other type II topoisomerases remain speculative. We used magnetic tweezers to measure the relaxation rates of single and multiple DNA crossings by Topo IV. These measurements allowed us to determine unambiguously the relative importance of DNA crossing geometry and enzymatic processivity in chiral discrimination by Topo IV. Our results indicate that Topo IV binds and passes DNA strands juxtaposed in a nearly perpendicular orientation and that relaxation of negative supercoiled DNA is perfectly distributive. Together, these results suggest that chiral discrimination arises primarily from dramatic differences in the processivity of relaxing positive and negative supercoiled DNA: Topo IV is highly processive on positively supercoiled DNA, whereas it is perfectly distributive on negatively supercoiled DNA. These results provide fresh insight into topoisomerase mechanisms and lead to a model that reconciles contradictory aspects of previous findings while providing a framework to interpret future results. C1 [Neuman, K. C.; Charvin, G.; Bensimon, D.; Croquette, V.] Ecole Normale Super, Lab Phys Stat, F-75005 Paris, France. RP Neuman, KC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM neumankc@nhlbi.nih.gov RI Neuman, Keir/F-7400-2011; Bensimon, David/E-7768-2015; OI Neuman, Keir/0000-0002-0863-5671; Bensimon, David/0000-0003-1971-9907; charvin, gilles/0000-0002-6852-6952 FU Nationale de la Recherche Science and Association pour la Recherche sur le Cancer; Human Frontiers Science Program; Intramural Program of the National Heart, Lung, and Blood Institute, National Institutes of Health FX We thank Giuseppe Lia and Elise Praly for DNA constructs, in addition to Omar Saleh, Timothee Lionet, Jean-Pierre Dumas, Jean-Francois Allemand, Alexander Vologodskii, James Berger, Joachim Roca, Anthony Maxwell, and Neil Osheroff for enlightening discussions. We thank Grace Liou, Richard Neuman, Kristina Herbert, Ashley Hardin, and Yeonee Seol for critical reading of the manuscript. This work was supported by the Centre Nationale de la Recherche Science and Association pour la Recherche sur le Cancer. K. C. N. was supported by a long-term fellowship from the Human Frontiers Science Program and by the Intramural Program of the National Heart, Lung, and Blood Institute, National Institutes of Health. NR 31 TC 48 Z9 48 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2009 VL 106 IS 17 BP 6986 EP 6991 DI 10.1073/pnas.0900574106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438VS UT WOS:000265584500023 PM 19359479 ER PT J AU Ben-Sasson, SZ Hu-Li, J Quiel, J Cauchetaux, S Ratner, M Shapira, I Dinarello, CA Paul, WE AF Ben-Sasson, Shlomo Z. Hu-Li, Jane Quiel, Juan Cauchetaux, Stephane Ratner, Maya Shapira, Ilana Dinarello, Charles A. Paul, William E. TI IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokines; inflammasome; Th1; Th17; Th2 ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; HOST-DEFENSE; DENDRITIC CELLS; EXPRESSION; RESPONSES; MICE; ACTIVATION; INFECTION; MECHANISM; IMMUNITY AB IL-1 causes a marked increase in the degree of expansion of naive and memory CD4 T cells in response to challenge with their cognate antigen. The response occurs when only specific CD4 T cells can respond to IL-1 beta, is not induced by a series of other cytokines and does not depend on IL-6 or CD-28. When WT cells are primed in IL-1R1(-/-) recipients, IL-1 increases the proportion of cytokine-producing transgenic CD4 T cells, especially IL-17- and IL-4-producing cells, strikingly increases serum IgE levels and serum IgG1 levels. IL-1 beta enhances antigen-mediated expansion of in vitro primed Th1, Th2, and Th17 cells transferred to IL-1R1(-/-) recipients. The IL-1 receptor antagonist diminished responses to antigen plus lipopolysaccharide (LPS) by approximate to 55%. These results indicate that IL-1 beta signaling in T cells markedly induces robust and durable primary and secondary CD4 responses. C1 [Ben-Sasson, Shlomo Z.; Hu-Li, Jane; Quiel, Juan; Cauchetaux, Stephane; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ben-Sasson, Shlomo Z.; Ratner, Maya; Shapira, Ilana] Hebrew Univ Jerusalem, Hadassah Med Ctr, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. [Dinarello, Charles A.] Univ Colorado, Hlth Sci Ctr, Dept Infect Dis, Denver, CO 80045 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We thank Dr. George Punkosdy, Laboratory of Immunology/ National Institute of Allergy and Infectious Diseases, for his generous help with the LCMV peptide immunization and tetramer staining. This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 36 TC 186 Z9 190 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 2009 VL 106 IS 17 BP 7119 EP 7124 DI 10.1073/pnas.0902745106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 438VS UT WOS:000265584500046 PM 19359475 ER PT J AU Cao, C Huang, XS Han, YY Wan, YS Birnbaumer, L Feng, GS Marshall, J Jiang, MS Chu, WM AF Cao, Cong Huang, Xuesong Han, Yuyuan Wan, Yinsheng Birnbaumer, Lutz Feng, Geng-Sheng Marshall, John Jiang, Meisheng Chu, Wen-Ming TI G alpha(i1) and G alpha(i3) Are Required for Epidermal Growth Factor-Mediated Activation of the Akt-mTORC1 Pathway SO SCIENCE SIGNALING LA English DT Article ID FOXO TRANSCRIPTION FACTORS; HETEROTRIMERIC G-PROTEINS; PERTUSSIS-TOXIN; FACTOR RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE HYDROLYSIS; SIGNALING PATHWAYS; KINASE ACTIVATION; RAT HEPATOCYTES; CELL-MIGRATION AB The precise mechanism whereby epidermal growth factor (EGF) activates the serine-threonine kinase Akt and the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) remains elusive. Here, we report that the alpha subunits of the heterotrimeric guanine nucleotide-binding proteins (G proteins) G alpha(i1) and G alpha(i3) are critical for this activation process. Both G alpha(i1) and G alpha(i3) formed complexes with growth factor receptor binding 2 (Grb2)-associated binding protein 1 (Gab1) and the EGF receptor (EGFR) and were required for the phosphorylation of Gab1 and its subsequent interaction with the p85 subunit of phosphatidylinositol 3-kinase in response to EGF. Loss of G alpha(i1) and G alpha(i3) severely impaired the activation of Akt and of p70 S6 kinase and 4E-BP1, downstream targets of mTORC1, in response to EGF, heparin-binding EGF-like growth factor, and transforming growth factor alpha, but not insulin, insulin-like growth factor, or platelet-derived growth factor. In addition, ablation of G alpha(i1) and G alpha(i3) largely inhibited EGF-induced cell growth, migration, and survival, and the accumulation of cyclin D1. Overall, this study suggests that G alpha(i1) and G alpha(i3) lie downstream of EGFR, but upstream of Gab1-mediated activation of Akt and mTORC1, thus revealing a role for G alpha(i) proteins in mediating EGFR signaling. C1 [Cao, Cong; Huang, Xuesong; Han, Yuyuan; Chu, Wen-Ming] Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. [Cao, Cong; Chu, Wen-Ming] Brown Univ, Pathobiol Grad Program, Providence, RI 02912 USA. [Wan, Yinsheng] Providence Coll, Dept Biol, Providence, RI 02918 USA. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Feng, Geng-Sheng] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Marshall, John] Brown Univ, Dept Mol Pharmacol Physiol & Biotechnol, Providence, RI 02912 USA. [Jiang, Meisheng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Chu, WM (reprint author), Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. EM wen-ming_chu@brown.edu FU U.S. Department of Defense [PR054819]; NIH [AI054128, DK069771, P20 RR016457]; National Institute of Environmental Health Sciences, NIH; Brown University FX We thank J. Wands for discussion. This work was supported by grants from the U.S. Department of Defense (PR054819) and NIH (AI054128) to W.M.C., NIH (DK069771) to M.J., NIH (P20 RR016457) to Y.W., and in part from the Intramural Research program of the National Institute of Environmental Health Sciences, NIH, to L.B. C.C. is partially supported by the pathobiology Graduate Program at Brown University. W.M.C. is a scholar of the Leukemia and Lymphoma Society. NR 51 TC 43 Z9 43 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD APR 28 PY 2009 VL 2 IS 68 AR ra17 DI 10.1126/scisignal.2000118 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 567VH UT WOS:000275474400004 PM 19401591 ER PT J AU Hildesheim, A Schiffman, M Solomon, D Wacholder, S Rodriguez, AC Herrero, R AF Hildesheim, Allan Schiffman, Mark Solomon, Diane Wacholder, Sholom Rodriguez, Ana Cecilia Herrero, Rolando TI Response to "Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines" by Verstraeten et al. SO VACCINE LA English DT Letter C1 [Hildesheim, Allan; Schiffman, Mark; Solomon, Diane; Wacholder, Sholom] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hildesheim, Allan; Schiffman, Mark; Solomon, Diane; Wacholder, Sholom] Natl Canc Inst, Canc Prevent Div, Bethesda, MD USA. [Rodriguez, Ana Cecilia; Herrero, Rolando] Fdn INCIENSA, San Jose, CA USA. RP Hildesheim, A (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM hildesha@mail.nih.gov RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU Intramural NIH HHS [Z01 CP010177-07] NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 28 PY 2009 VL 27 IS 19 BP 2529 EP 2529 DI 10.1016/j.vaccine.2009.01.028 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 440YK UT WOS:000265735400001 PM 19186195 ER PT J AU Eshleman, SH Laeyendecker, O Parkin, N Huang, W Chappey, C Paquet, AC Serwadda, D Reynolds, SJ Kiwanuka, N Quinn, TC Grayg, R Wawer, M AF Eshleman, Susan H. Laeyendecker, Oliver Parkin, Neil Huang, Wei Chappey, Colombe Paquet, Agnes C. Serwadda, David Reynolds, Steven J. Kiwanuka, Noah Quinn, Thomas C. Grayg, Ronald Wawer, Maria TI Antiretroviral drug susceptibility among drug-naive adults with recent HIV infection in Rakai, Uganda SO AIDS LA English DT Article DE antiretroviral drug; hypersusceptibility; phenotype; resistance; subtype; Uganda ID IMMUNODEFICIENCY-VIRUS TYPE-1; SINGLE-DOSE NEVIRAPINE; TO-CHILD TRANSMISSION; REVERSE-TRANSCRIPTASE; SUBTYPE-C; RESISTANCE MUTATIONS; PROTEASE INHIBITORS; PREVENTION; SEQUENCES; VARIANTS AB Objective: To analyze antiretroviral drug susceptibility in HIV from recently infected adults in Rakai, Uganda, prior to the availability of antiretroviral drug treatment. Methods: Samples obtained at the time of HIV seroconversion (1998-2003) were analyzed using the GeneSeq HIV and PhenoSense HIV assays (Monogram Biosciences, Inc., South San Francisco, California, USA). Results: Test results were obtained for 104 samples (subtypes: 26A, 1C, 66D, 9A/D, 1C/D, 1 intersubtype recombinant). Mutations used for genotypic surveillance of transmitted antiretroviral drug resistance were identified in six samples: three had nucleoside reverse transcriptase inhibitor (NRTI) surveillance mutations (two had M41L, one had K219R), and three had protease inhibitor surveillance mutations (I47V, F53L, N88D); none had nonnucleoside reverse transcriptase inhibitor (NNRTI) Surveillance mutations. Other resistance-associated mutations were identified in some samples. However, none of the samples had a sufficient number of mutations to predict reduced antiretroviral drug susceptibility. Ten (9.6%) of the samples had reduced phenotypic susceptibility to at least one drug (one had partial susceptibility to didanosine, one had nevirapine resistance, and eight had resistance or partial susceptibility to at least one protease inhibitor). Fifty-three (51%) of the samples had hypersusceptibility to at least one drug (seven had zidovudine hypersusceptibility, 28 had NNRTI hypersusceptibility, 34 had protease inhibitor hypersusceptibility). Delavirdine hypersusceptibility was more frequent in subtype A than D. In subtype D, efavirenz hypersusceptibility was associated with substitutions at codon 11 in HIV-reverse transcriptase. Conclusion: Phenotyping detected reduced antiretroviral drug susceptibility and hypersusceptibility in HIV from some antiretroviral-naive Ugandan adults that was not predicted by genotyping. Phenotyping may complement genotyping for analysis of antiretroviral drug susceptibility in populations with nonsubtype B HIV infection. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Eshleman, Susan H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Laeyendecker, Oliver; Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Laeyendecker, Oliver; Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Parkin, Neil; Huang, Wei; Chappey, Colombe; Paquet, Agnes C.] Monogram Biosci Inc, San Francisco, CA USA. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Kiwanuka, Noah] Rakai Hlth Sci Program, Rakai, Uganda. [Grayg, Ronald; Wawer, Maria] Johns Hopkins Univ, Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA. RP Eshleman, SH (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 646 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. EM seshlem@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; OI Laeyendecker, Oliver/0000-0002-6429-4760 FU HIV Epidemiology and Behaviors, Rakai, Uganda, NIH, NICHD [R01-01050180-01, Q2II2007]; National Institute of Allergy and Infectious Diseases (NIAID); National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); NIH, DHHS [U01-AI-068613 to SHE]; United States Army Medical Research and Material Command Cooperative Agreement [DAMD17-98-2-8007]; Henry M. Jackson Foundation [5D43TW00010] FX Sources of support: ARY Effects on HIV Epidemiology and Behaviors, Rakai, Uganda, NIH, NICHD, (R01-01050180-01 to MW), Division of Intramural Research, NIAID, Science Applications International Corporation (SAIC) subcontract, NIH, NIAID (#Q2II2007 to TCQ, SJR, and OL), The HIV Prevention Trials Network (HPTN) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH), and Office of AIDS Research, of the NIH, DHHS (U01-AI-068613 to SHE). Data collection was supported by Department of the Army, United States Army Medical Research and Material Command Cooperative Agreement DAMD17-98-2-8007, and the Henry M. Jackson Foundation, grant 5D43TW00010. NR 27 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 27 PY 2009 VL 23 IS 7 BP 845 EP 852 DI 10.1097/QAD.0b013e328327957a PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 438OJ UT WOS:000265564600012 PM 19276794 ER PT J AU Jiao, L Mitrou, PN Reedy, J Graubard, BI Hollenbeck, AR Schatzkin, A Stolzenberg-Solomon, R AF Jiao, Li Mitrou, Panagiota N. Reedy, Jill Graubard, Barry I. Hollenbeck, Albert R. Schatzkin, Arthur Stolzenberg-Solomon, Rachael TI A Combined Healthy Lifestyle Score and Risk of Pancreatic Cancer in a Large Cohort Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MEDITERRANEAN DIETARY PATTERN; POPULATION; INFLAMMATION; VALIDATION; ADHERENCE; OBESITY; ADULTS; MEN AB Background: Smoking, alcohol use, diet, body mass index (calculated as weight in kilograms divided by height in meters squared), and physical activity have been studied independently in relation to pancreatic cancer. We generated a healthy lifestyle score to investigate their joint effect on risk of pancreatic cancer. Methods: In the prospective National Institutes of Health-AARP Diet and Health Study, a total of 450 416 participants aged 50 to 71 years completed the baseline food frequency questionnaire (1995-1996) eliciting diet and lifestyle information and were followed up through December 31, 2003. We identified 1057 eligible incident pancreatic cancer cases. Participants were scored on 5 modifiable lifestyle factors as unhealthy (0 points) or healthy (1 point) on the basis of current epidemiologic evidence. Participants received 1 point for each respective lifestyle factor: nonsmoking, limited alcohol use, adherence to the Mediterranean dietary pattern, body mass index (>= 18 and < 25), or regular physical activity. A combined score (0-5 points) was calculated by summing the scores of the 5 factors. Cox proportional hazards regression models were used to estimate relative risk (95% confidence interval) for pancreatic cancer. Results: Compared with the lowest combined score (0 points), the highest score (5 points) was associated with a 58% reduction in risk of developing pancreatic cancer in all participants (relative risk, 0.42; 95% confidence interval, 0.26-0.66; P(trend) <. 001). Scores of less than 5 points were associated with 27% of pancreatic cancer cases in our population. Conclusion: Findings from this large study suggest that having a high score, as opposed to a low score, on an index combining 5 modifiable lifestyle factors substantially reduces the risk of developing pancreatic cancer. C1 [Jiao, Li; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael] NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Graubard, Barry I.] NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Reedy, Jill] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Reedy, Jill] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. [Mitrou, Panagiota N.] World Canc Res Fund Int, London, England. [Mitrou, Panagiota N.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Jiao, L (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Executive Blvd,Executive Plaza S,Room 3032, Rockville, MD 20852 USA. EM jiaol@mail.nih.gov; stolzenr@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 27 TC 64 Z9 65 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 27 PY 2009 VL 169 IS 8 BP 764 EP 770 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 438FE UT WOS:000265540500006 PM 19398688 ER PT J AU Korde, LA Micheli, A Smith, AW Venzon, D Prindiville, SA Drinkard, B Sebring, N Smith, MD Zujewski, JA Eng-Wong, J AF Korde, Larissa A. Micheli, Amy Smith, Ashley W. Venzon, David Prindiville, Sheila A. Drinkard, Bart Sebring, Nancy Smith, Marcia D. Zujewski, Jo Anne Eng-Wong, Jennifer TI Recruitment to a physical activity intervention study in women at increased risk of breast cancer SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; BLOOD-PRESSURE; PREVENTION; TAMOXIFEN; EXERCISE; SURVIVORS; HEALTH; OVERWEIGHT; MANAGEMENT AB Background: Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging. Methods: We conducted an analysis of recruitment techniques used for a prospective, randomized pilot study of physical activity in women at risk of breast cancer. We evaluated differences in proportion of eligible patients, enrolled patients, and successful patients identified by each individual recruitment method. The Fisher-Freeman-Halton test (an extension of Fisher's exact test from 2 x 2 tables to general row by column tables) was used to compare the success of different recruitment strategies. Results: We received 352 inquiries from women interested in participating, of whom 171 (54%) were eligible. Ninety-nine women completed a baseline activity evaluation, and 58 (34% of eligible; 16% of total inquiries) were randomized. Recruitment methods fell into three broad categories: media techniques, direct contact with potential participants, and contacts with health care providers. Recruitment strategies differed significantly in their ability to identify eligible women (p = 0.01), and women who subsequently enrolled in the study (p = 0.02). Conclusion: Recruitment techniques had varying success. Our data illustrate the challenges in recruiting to behavior modification studies, and provide useful information for tailoring future recruitment efforts for lifestyle intervention trials. C1 [Korde, Larissa A.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA. [Micheli, Amy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Smith, Ashley W.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Venzon, David] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Bethesda, MD 20892 USA. [Drinkard, Bart; Sebring, Nancy; Smith, Marcia D.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Zujewski, Jo Anne] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Eng-Wong, Jennifer] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. RP Korde, LA (reprint author), NCI, Clin Genet Branch, Bethesda, MD 20892 USA. EM kordel@mail.nih.gov; Amy.Micheli@jefferson.edu; smithas@mail.nih.gov; venzond@mail.nih.gov; prindivs@mail.nih.gov; bdrinkard@mail.nih.gov; nsebring@mail.nih.gov; mdsmith1@mail.nih.gov; zujewskj@mail.nih.gov; je95@georgetown.edu FU NIH; National Cancer Institute; Center for Cancer Research and Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and Division of Cancer Epidemiology and Genetics. NR 33 TC 5 Z9 5 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD APR 27 PY 2009 VL 9 AR 27 DI 10.1186/1471-2288-9-27 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 455KW UT WOS:000266759500001 PM 19397816 ER PT J AU Kim, SB Cai, C Faust, MD Trenkle, WC Sweigart, DA AF Kim, Sang Bok Cai, Chen Faust, Marcus D. Trenkle, William C. Sweigart, Dwight A. TI A Water-Stable Organometallic Rhodium Quinone Catalyst and Its Recyclability SO ORGANOMETALLICS LA English DT Article ID ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; ARYL BORONIC ACIDS; ARYLBORONIC ACIDS; ALKENYLBORONIC ACIDS; CONJUGATE ADDITION; 1,4-ADDITION; ALDEHYDES; ESTERS; ENONES AB When the insoluble dimers [Rh(COD)X](2) (X = OH(-), Cl(-)) are in. contact with a basic aqueous solution of hydroquinone dianion, the precipitate dissolves to afford (benzoquinone)Rh(COD)(-) (2). Complex 2 is very stable and can be recycled many times as a homogeneous catalyst for the conjugate addition of boronic acids to olefins. NMR spectra suggest their the catalytic species is indeed the quinone complex 2. C1 [Kim, Sang Bok; Cai, Chen; Faust, Marcus D.; Sweigart, Dwight A.] Brown Univ, Dept Chem, Providence, RI 02912 USA. [Trenkle, William C.] NIDDK, NIH, DHHS, Bethesda, MD 20814 USA. RP Sweigart, DA (reprint author), Brown Univ, Dept Chem, Providence, RI 02912 USA. EM Dwight_Sweigart@brown.edu FU American Chemical Society; NIH [CHE-0308640] FX We are grateful to the donors of the Petroleum Research Fund, administered by the American Chemical Society, to the intramural research program at the NIH, National Institute of Diabetes and Digesfive and Kidney Diseases (W.C.T.), and to the National Science Foundation (No. CHE-0308640) for support of this research. NR 18 TC 7 Z9 7 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0276-7333 J9 ORGANOMETALLICS JI Organometallics PD APR 27 PY 2009 VL 28 IS 8 BP 2625 EP 2628 DI 10.1021/om900084y PG 4 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 435ZZ UT WOS:000265383700033 ER PT J AU Gorbach, AM Leeser, DB Wang, HL Tadaki, DK Fernandez, C DeStephano, D Hale, D Kirk, AD Gage, FA Elster, EA AF Gorbach, Alexander M. Leeser, David B. Wang, Hengliang Tadaki, Douglas K. Fernandez, Carlos DeStephano, David Hale, Douglas Kirk, Allan D. Gage, Fred A. Elster, Eric A. TI Assessment of Cadaveric Organ Viability During Pulsatile Perfusion Using Infrared Imaging SO TRANSPLANTATION LA English DT Article DE Infrared imaging; Pulsatile perfusion; Viability ID MACHINE PERFUSION; PRESERVATION; KIDNEYS AB Assessment of pulsatile perfusion (PP) is limited to measurements of flow (V) and resistance (R). We investigated infrared (IR) imaging during PP as a means for precise organ assessment. IR was used to monitor 10 porcine kidneys during 18 hr of PP in an uncontrolled Donation after Cardiac Death model. An IR camera (Lockheed Martin) was focused on the anterior surfaces of the kidneys. The degree of temperature homogeneity was compared with standard measurements of V and R. IR thermal images correlated with V and R (R=0.92, P<0.001). IR detected an increase in homogeneity during PP by comparing standard deviation differences before and after PP (P=0.002), which was not evident by standard measurements of V and R. Finally, IR assessment allowed for measurement of dynamic changes in perfusion. C1 [Elster, Eric A.] USN, Med Res Ctr, Regenerat Med Dept, Silver Spring, MD 20910 USA. [Elster, Eric A.] Natl Naval Med Ctr, Dept Surg, Bethesda, MD USA. [Kirk, Allan D.] Emory Univ Hosp, Emory Transplant Ctr, Atlanta, GA 30322 USA. [Hale, Douglas] Univ Florida, Med Ctr, Div Transplantat, Jacksonville, FL 32209 USA. [Fernandez, Carlos; DeStephano, David] Washington Reg Transplant Consortium, Fairfax, VA USA. [Tadaki, Douglas K.; Elster, Eric A.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. [Leeser, David B.] New York Presbyterian Hosp, Weill Cornell Med Ctr, Weill Cornell Med Coll, Dept Surg, New York, NY USA. [Gorbach, Alexander M.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Elster, EA (reprint author), USN, Med Res Ctr, Regenerat Med Dept, Silver Spring, MD 20910 USA. EM eric.elster@med.navy.mil RI Kirk, Allan/B-6905-2012 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health [602227D.0483.01.A0518] FX This research was supported in part by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. In addition, this work was supported by work unit number: 602227D.0483.01.A0518 (MFEL). NR 7 TC 4 Z9 4 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 2009 VL 87 IS 8 BP 1163 EP 1166 DI 10.1097/TP.0b013e31819e3e02 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 437BU UT WOS:000265461600010 PM 19384162 ER PT J AU Bozhok, Y Greerebaum, E Bogdanova, TI McConnell, RJ Zelinskaya, A Brenner, AV Zurnadzhy, LY Zablotska, L Tronko, MD Hatch, M AF Bozhok, Yuriy Greerebaum, Ellen Bogdanova, Tetyana I. McConnell, Robert J. Zelinskaya, Anna Brenner, Alina V. Zurnadzhy, Lyudmyla Y. Zablotska, Lydia Tronko, Mykola D. Hatch, Maureen TI NA Cohort Study of Thyroid Cancer and Other Thyroid Diseases After the Chernobyl Accident Cytohistopathologic Correlation and Accuracy of Fine-Needle Aspiration Biopsy in Nodules Detected During the First Screening in Ukraine (1998-2000) SO CANCER CYTOPATHOLOGY LA English DT Article DE fine-needle aspiration biopsy; follicular neoplasm; follicular thyroid cancer; papillary thyroid cancer; Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases; Chernobyl; Chernobyl radiation-induced cancer ID FOLLICULAR NEOPLASM; CYTOLOGY; CARCINOMA; DIAGNOSIS; PREVALENCE; MALIGNANCY; CHILDHOOD AB BACKGROUND: The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to (131)I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown. METHODS: During the first screening cycle (1998-2000),13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated. RESULTS: All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but I of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%. CONCLUSIONS: Among children and adolescents who were exposed to 131 1 after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations. Cancer (Cancer Cytopathol) 2009;117:73-81. Published 2009 by the American Cancer Society. C1 [McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Thyroid Ctr, New York, NY 10032 USA. [Bozhok, Yuriy; Bogdanova, Tetyana I.; Zelinskaya, Anna; Zurnadzhy, Lyudmyla Y.; Tronko, Mykola D.] Inst Endocrinol & Metab, Kiev, Ukraine. [Greerebaum, Ellen] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. [Brenner, Alina V.; Hatch, Maureen] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Zablotska, Lydia] Univ Calif San Francisco, Sch Med, Dept Epidemiol, San Francisco, CA USA. RP McConnell, RJ (reprint author), Columbia Univ, Coll Phys & Surg, Thyroid Ctr, Herbert Irving Pavil,Room 210,161 Ft Washington A, New York, NY 10032 USA. EM rjm1@columbia.edu FU National Cancer Institute, Department of Health and Human Service [NO1-CP-21, 178] FX This study was funded under the Contract NO1-CP-21, 178 by the National Cancer Institute, Department of Health and Human Service. The Department of Energy provided funding at the initial stage of the study, and the Nuclear Regulatory Commission provided the initial funds for purchase of equipment. NR 36 TC 7 Z9 7 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2009 VL 117 IS 2 BP 73 EP 81 DI 10.1002/cncy.20002 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 430RJ UT WOS:000265005900001 PM 19365829 ER PT J AU Hoshino, Y Pesnicak, L Straus, SE Cohen, JI AF Hoshino, Yo Pesnicak, Lesley Straus, Stephen E. Cohen, Jeffrey I. TI Impairment in reactivation of a latency associated transcript (LAT)-deficient HSV-2 is not solely dependent on the latent viral load or the number of CD8(+) T cells infiltrating the ganglia SO VIROLOGY LA English DT Article DE Herpes simplex virus; Latency associated transcripts; Reactivation; CD8(+) T cells; Viral load; Latency; Wide range inocula ID HERPES-SIMPLEX-VIRUS; RABBIT EYE MODEL; TYPE-1 LATENCY; IN-VIVO; TRIGEMINAL GANGLIA; SENSORY NEURONS; GENITAL HERPES; INFECTED NEURONS; GENE-EXPRESSION; GUINEA-PIGS AB The HSV latency-associated transcript (LAT) is abundantly expressed during virus latency. Previous studies have shown that the latent viral load and CD8(+) T cells in ganglia influence the rate of reactivation of HSV. While LAT is important for efficient reactivation and establishment of latency, it is uncertain how LAT affects either the HSV latent viral load or CD8(+) T cell infiltration of ganglia. We infected mice with LAT-deficient or LAT-restored HSV-2 at a wide range of inocula. We found that the reduced rate of spontaneous ex-vivo reactivation of the LAT-deficient virus Was not associated with a higher number of CD8(+) T cells in the ganglia. Reactivation rates were lower for LAT-deficient than LAT restored HSV-2 even when the latent viral loads were similar, indicating that differences in reactivation were not solely dependent on the latent viral load. Therefore, LAT likely has additional functions important for reactivation. (C) 2009 Published by Elsevier Inc. C1 [Hoshino, Yo; Pesnicak, Lesley; Straus, Stephen E.; Cohen, Jeffrey I.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM YHoshino@niaid.nih.gov; LPesnicak@niaid.nih.gov; jcohen@niaid.nih.gov FU Intramural program of the National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural program of the National Institute of Allergy and Infectious Diseases. We thank Philip Krause and Kening Wang for the viruses used and for reviewing the manuscript. We also thank Dean Follmann, Biostatistics Research Branch, MAID for statistical advice. NR 46 TC 5 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2009 VL 387 IS 1 BP 193 EP 199 DI 10.1016/j.virol.2009.02.004 PG 7 WC Virology SC Virology GA 438NI UT WOS:000265561800022 PM 19269661 ER PT J AU Piontkivska, H Yang, MQ Larkin, DM Lewin, HA Reecy, J Elnitski, L AF Piontkivska, Helen Yang, Mary Q. Larkin, Denis M. Lewin, Harris A. Reecy, James Elnitski, Laura TI Cross-species mapping of bidirectional promoters enables prediction of unannotated 5 ' UTRs and identification of species-specific transcripts SO BMC GENOMICS LA English DT Article ID HUMAN GENOME; EVOLUTION; GENE; SEQUENCE AB Background: Bidirectional promoters are shared regulatory regions that influence the expression of two oppositely oriented genes. This type of regulatory architecture is found more frequently than expected by chance in the human genome, yet many specifics underlying the regulatory design are unknown. Given that the function of most orthologous genes is similar across species, we hypothesized that the architecture and regulation of bidirectional promoters might also be similar across species, representing a core regulatory structure and enabling annotation of these regions in additional mammalian genomes. Results: By mapping the intergenic distances of genes in human, chimpanzee, bovine, murine, and rat, we show an enrichment for pairs of genes equal to or less than 1,000 bp between their adjacent 5' ends ("head-to-head") compared to pairs of genes that fall in the same orientation ("head-to-tail") or whose 3' ends are side-by-side ("tail-to-tail"). A representative set of 1,369 human bidirectional promoters was mapped to orthologous sequences in other mammals. We confirmed predictions for 5' UTRs in nine of ten manual picks in bovine based on comparison to the orthologous human promoter set and in six of seven predictions in human based on comparison to the bovine dataset. The two predictions that did not have orthology as bidirectional promoters in the other species resulted from unique events that initiated transcription in the opposite direction in only those species. We found evidence supporting the independent emergence of bidirectional promoters from the family of five RecQ helicase genes, which gained their bidirectional promoters and partner genes independently rather than through a duplication process. Furthermore, by expanding our comparisons from pairwise to multispecies analyses we developed a map representing a core set of bidirectional promoters in mammals. Conclusion: We show that the orthologous positions of bidirectional promoters provide a reliable guide to directly annotate over one thousand regulatory regions in sequences of mammalian genomes, while also serving as a useful tool to predict 5' UTR positions and identify genes that are novel to a single species. C1 [Yang, Mary Q.; Elnitski, Laura] NHGRI, NIH, Rockville, MD 20852 USA. [Piontkivska, Helen] Kent State Univ, Dept Biol Sci, Kent, OH 44242 USA. [Larkin, Denis M.; Lewin, Harris A.] Univ Illinois, Dept Anim Sci, Urbana, IL 61821 USA. [Lewin, Harris A.] Univ Illinois, Inst Genome Biol, Urbana, IL 61821 USA. [Reecy, James] Iowa State Univ, Dept Anim Sci, Ames, IA 50011 USA. RP Elnitski, L (reprint author), NHGRI, NIH, Rockville, MD 20852 USA. EM opiontki@kent.edu; yangma@mail.nih.gov; dlarkin@uiuc.edu; h-lewin@UIUC.EDU; jreecy@iastate.edu; elnitski@mail.nih.gov FU National Human Genome Research Institute; U. S. National Institutes of Health; Ohio Board of Regents/Kent State research challenge grant FX MQY and LE are sponsored by the Intramural program of the National Human Genome Research Institute, U. S. National Institutes of Health. HP was partially supported by an Ohio Board of Regents/Kent State research challenge grant. We thank Dr. Jen Harrow at the Wellcome Trust Sanger Institute whom supervised the re- annotation of human transcripts in the Vega pipeline. Editorial assistance was from the NIH Fellows Editorial Board. NR 24 TC 18 Z9 20 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 24 PY 2009 VL 10 AR 189 DI 10.1186/1471-2164-10-189 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 456PA UT WOS:000266858100002 PM 19393065 ER PT J AU Norris, JD Joseph, JD Sherk, AB Juzumiene, D Turnbull, PS Rafferty, SW Cui, HX Anderson, E Fan, DJ Dye, DA Deng, X Kazmin, D Chang, CY Willson, TM McDonnell, DP AF Norris, John David Joseph, James David Sherk, Andrea Barreto Juzumiene, Dalia Turnbull, Philip Stewart Rafferty, Stephen William Cui, Huaxia Anderson, Erin Fan, Daju Dye, Delita Arnelle Deng, Xiang Kazmin, Dmitri Chang, Ching-Yi Willson, Timothy Mark McDonnell, Donald Patrick TI Differential Presentation of Protein Interaction Surfaces on the Androgen Receptor Defines the Pharmacological Actions of Bound Ligands SO CHEMISTRY & BIOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; PROSTATE-CANCER CELLS; PEPTIDE ANTAGONISTS; GENE-EXPRESSION; BINDING DOMAIN; BREAST-CANCER; POSTMENOPAUSAL WOMEN; DISTINCT MECHANISMS; MODULATORS SARMS; STRUCTURAL BASIS AB The pharmacological activity of different nuclear receptor ligands is reflected by their impact on receptor structure. Thus, we asked whether differential presentation of protein-protein interaction surfaces on the androgen receptor (AR), a surrogate assay of receptor conformation, could be used in a prospective manner to define the pharmacological activity of bound ligands. To this end, we identified over 150 proteins/polypeptides whose ability to interact with AR is influenced in a differential manner by ligand binding. The most discriminatory of these protein-AR interactions were used to develop a robust compound-profiling tool that enabled the separation of ligands into functionally distinguishable classes. Importantly, the ligands; within each class exhibited similar pharmacological activities, a result that highlights the relationship between receptor structure and activity and provides direction for the discovery of novel AR modulators. C1 [Norris, John David; Joseph, James David; Sherk, Andrea Barreto; Juzumiene, Dalia; Cui, Huaxia; Anderson, Erin; Fan, Daju; Dye, Delita Arnelle; Deng, Xiang; Kazmin, Dmitri; Chang, Ching-Yi; McDonnell, Donald Patrick] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Turnbull, Philip Stewart; Rafferty, Stephen William; Dye, Delita Arnelle; Willson, Timothy Mark] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. [Deng, Xiang] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Juzumiene, Dalia] Affinergy Inc, Durham, NC 27713 USA. RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. EM donald.mcdonnell@duke.edu FU NIH [CA139818]; GlaxoSmithKiine (GSK) FX Supported by a grant from the NIH (CA139818) and sponsored research support from GlaxoSmithKiine (GSK). We would like to thank Bajin Han and Tianshun Xu (GSK) for providing levator ani tissue. NR 48 TC 33 Z9 33 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD APR 24 PY 2009 VL 16 IS 4 BP 452 EP 460 DI 10.1016/j.chembiol.2009.01.016 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442CH UT WOS:000265816900012 PM 19389631 ER PT J AU Amir, S Wang, RX Simons, JW Mabjeesh, NJ AF Amir, Sharon Wang, Ruoxiang Simons, Jonathan W. Mabjeesh, Nicola J. TI SEPT9_v1 Up-regulates Hypoxia-inducible Factor 1 by Preventing Its RACK1-mediated Degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; HUMAN BREAST-CANCER; FACTOR 1-ALPHA; PROSTATE-CANCER; TRANSCRIPTIONAL ACTIVITY; EXPRESSION; HSP90; HIF-1-ALPHA; PATHWAY; GENE AB A critical mediator of the cellular response to hypoxia is hypoxia-inducible factor 1 (HIF-1). Increased levels of HIF-1 alpha are often associated with increased tumor metastasis, therapeutic resistance, and poorer prognosis. We recently identified a novel interaction between HIF-1 alpha and the mammalian septin family member, SEPT9_v1. Septins are a highly conserved family of GTP-binding cytoskeletal proteins that are implicated in multiple cellular functions, including cell division and oncogenesis. SEPT9_v1 binds and stabilizes HIF-1 alpha protein and stimulates HIF-1 transcriptional activity. SEPT9_v1-HIF-1 activation promotes tumor growth and angiogenesis. The structural and functional relationships between SEPT9_v1 and HIF-1 alpha were analyzed. We found that SEPT9_v1 binds specifically with HIF-1 alpha but not with HIF2 alpha. The GTPase domain of SEPT9_v1 was identified as essential for HIF-1 alpha binding. A GTPase domain-derived polypeptide, corresponding to amino acids 252-379, was able to disrupt HIF-1 alpha-SEPT9_v1 interaction and to inhibit HIF-1 transcriptional activity. SEPT9_v1 also protected HIF-1 alpha from degradation induced by HSP90 inhibition by preventing the interaction of HIF-1 alpha with the RACK1 protein, which promotes its oxygen-independent proteasomal degradation. In conclusion, a new mechanism of oxygen-independent activation of HIF-1 has been identified that is mediated by SEPT9_v1 blockade of RACK1 activity on HIF-1 alpha degradation. C1 [Amir, Sharon; Mabjeesh, Nicola J.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, Dept Urol,Prostate Canc Res Lab, IL-64239 Tel Aviv, Israel. [Wang, Ruoxiang] Emory Univ, Sch Med, Dept Urol, Atlanta, GA 30332 USA. [Simons, Jonathan W.] Prostate Canc Fdn, Santa Monica, CA 90401 USA. [Simons, Jonathan W.] Emory Univ, Dept Biomed Engn, NCI Ctr Nanotechnol Excellence, Atlanta, GA 30322 USA. [Simons, Jonathan W.] Georgia Inst Technol, Atlanta, GA 30322 USA. RP Mabjeesh, NJ (reprint author), Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Sackler Fac Med, Dept Urol,Prostate Canc Res Lab, 6 Weizmann St, IL-64239 Tel Aviv, Israel. EM nicolam@tasmc.health.gov.il FU M. K. Humanitarian Foundation; Prostate Cancer Foundation; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation FX This work was supported by the M. K. Humanitarian Foundation, Prostate Cancer Foundation, and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. NR 37 TC 25 Z9 26 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 2009 VL 284 IS 17 BP 11142 EP 11151 DI 10.1074/jbc.M808348200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437NP UT WOS:000265494500018 PM 19251694 ER PT J AU Ogilvie, RL SternJohn, JR Rattenbacher, B Vlasova, IA Williams, DA Hau, HH Blackshear, PJ Bohjanen, PR AF Ogilvie, Rachel L. SternJohn, Julius R. Rattenbacher, Bernd Vlasova, Irina A. Williams, Darlisha A. Hau, Heidi H. Blackshear, Perry J. Bohjanen, Paul R. TI Tristetraprolin Mediates Interferon-gamma mRNA Decay SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL-ACTIVATION; GENOME-WIDE ANALYSIS; RICH ELEMENT; HUMAN-MONOCYTES; BINDING PROTEIN; GENE-EXPRESSION; ELAV PROTEIN; STABILITY; PATHWAY; STABILIZATION AB Tristetraprolin (TTP) regulates expression at the level of mRNA decay of several cytokines, including the T cell-specific cytokine, interleukin-2. We performed experiments to determine whether another T cell-specific cytokine, interferon-gamma (IFN-gamma), is also regulated by TTP and found that T cell receptoractivatedTcells fromTTPknock-out mice overproduced IFN-gamma mRNA and protein compared with activated T cells from wild-type mice. The half-life of IFN-gamma mRNA was 23 min in anti-CD3-stimulated T cells from wild-type mice, whereas it was 51 min in anti-CD3-stimulated T cells from TTP knock-out mice, suggesting that the overexpression of IFN-gamma mRNA in TTP knock-out mice was due to stabilization of IFN-gamma mRNA. Insertion of a 70-nucleotide AU-rich sequence from the murine IFN-gamma 3'-untranslated region, which contained a high affinity binding site for TTP, into the 3'-untranslated region of a beta-globin reporter transcript conferred TTP-dependent destabilization on the beta-globin transcript. Together these results suggest that TTP binds to a functional AU-rich element in the 3'-untranslated region of IFN-gamma mRNA and mediates rapid degradation of the IFN-gamma transcript. Thus, TTP plays an important role in turning off IFN-gamma expression at the appropriate time during an immune response. C1 [SternJohn, Julius R.; Rattenbacher, Bernd; Vlasova, Irina A.; Williams, Darlisha A.; Bohjanen, Paul R.] Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, Minneapolis, MN 55455 USA. [Ogilvie, Rachel L.; Vlasova, Irina A.; Hau, Heidi H.; Bohjanen, Paul R.] Univ Minnesota, Ctr Immunol, Minneapolis, MN 55455 USA. [Ogilvie, Rachel L.; SternJohn, Julius R.; Rattenbacher, Bernd; Vlasova, Irina A.; Williams, Darlisha A.; Hau, Heidi H.; Bohjanen, Paul R.] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. [Bohjanen, Paul R.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Blackshear, Perry J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Bohjanen, PR (reprint author), Univ Minnesota, Ctr Infect Dis & Microbiol Translat Res, 2001 6th St S E,Rm 3-214,Delivery Code 2873, Minneapolis, MN 55455 USA. EM bohja001@umn.edu RI Bohjanen, Paul/B-2329-2015 OI Bohjanen, Paul/0000-0002-2772-3597 FU National Institutes of Health [R56AI057484, R01AI072068, T32AI007313, T32DE007288]; Lymphoma Research Foundation; Swiss National Science Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants R56AI057484, R01AI072068, T32AI007313, and T32DE007288. This work was also supported by fellowships from the Lymphoma Research Foundation and the Swiss National Science Foundation. NR 59 TC 59 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 24 PY 2009 VL 284 IS 17 BP 11216 EP 11223 DI 10.1074/jbc.M901229200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437NP UT WOS:000265494500025 PM 19258311 ER EF