FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Ingle, J Tu, D Shepherd, L Palmer, M Pater, J Goss, P AF Ingle, J. Tu, D. Shepherd, L. Palmer, M. Pater, J. Goss, P. TI NCICCTG MA.17: Intent to treat analysis (ITT) of randomized patients after a median follow-up of 54 months. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Mayo Clin, Rochester, MN USA. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 15S EP 15S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400056 ER PT J AU Ganz, PA Land, SR Wickerham, DL Lee, M Ritter, M Vogel, V Pajon, E Wade, JL Costantino, JP Wolmark, N AF Ganz, P. A. Land, S. R. Wickerham, D. L. Lee, M. Ritter, M. Vogel, V. Pajon, E. Wade, J. L. Costantino, J. P. Wolmark, N. TI The study of tamoxifen and raloxifene (STAR): First report of patient-reported outcomes (PROs) from the NSABP P-2 Breast Cancer Prevention Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Calif Los Angeles, Los Angeles, CA USA. NSABP, Ctr Biostat, Pittsburgh, PA USA. NSABP, Operat Off, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Cent Illinois CCOP, Decatur, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 18S EP 18S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400068 ER PT J AU Kimler, BF Ursin, G Fabian, CJ Anderson, JR Chamberlain, C Mayo, MS O'Shaughnessy, JA Lynch, HT Johnson, KA Browne, D AF Kimler, B. F. Ursin, G. Fabian, C. J. Anderson, J. R. Chamberlain, C. Mayo, M. S. O'Shaughnessy, J. A. Lynch, H. T. Johnson, K. A. Browne, D. TI Effect of the third generation selective estrogen receptor modulator arzoxifene on mammographic breast density. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ So Calif, Los Angeles, CA USA. Baylor Univ, Med Ctr, Dallas, TX USA. Creighton Univ, Omaha, NE 68178 USA. NCI, Bethesda, MD 20892 USA. RI Mayo, Matthew/E-3774-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 18S EP 18S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400070 ER PT J AU Geyer, CE Blyant, JL Romond, EH Ewer, MS Keefe, DL Shannon, RP Levine, TB Rastogi, P Swain, SM Wolmark, N AF Geyer, C. E., Jr. Blyant, J. L. Romond, E. H. Ewer, M. S. Keefe, D. L. Shannon, R. P. Levine, T. B. Rastogi, P. Swain, S. M. Wolmark, N. TI Update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)-> paclitaxel (T) vs. AC -> T with trastuzumab (H). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NSABP, Operat & Biostat Ctr, Pittsburgh, PA USA. Univ Kentucky, Markey Canc Ctr, Lexington, KY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 23S EP 23S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400088 ER PT J AU Anderson, WF Pfeiffer, RM Dores, GM Sherman, ME AF Anderson, W. F. Pfeiffer, R. M. Dores, G. M. Sherman, M. E. TI Bimodal breast cancer incidence patterns provide support for a dualistic model of mammary carcinogenesis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 26S EP 26S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400101 ER PT J AU Eng-Wong, J Chang, S Hursting, S Perkins, SN Nunez, N Hill, HL Bondy, M Li, D Singletary, SE AF Eng-Wong, J. Chang, S. Hursting, S. Perkins, S. N. Nunez, N. Hill, H. L. Bondy, M. Li, D. Singletary, S. E. TI Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Univ Texas, Austin, TX 78712 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 37S EP 37S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400147 ER PT J AU Denduluri, N Lee, JJ Walshe, JM Yang, SX Vatas, U Chow, CK Steinberg, SM Cox, MC Low, JA Swain, SM AF Denduluri, N. Lee, J. J. Walshe, J. M. Yang, S. X. Vatas, U. Chow, C. K. Steinberg, S. M. Cox, M. C. Low, J. A. Swain, S. M. TI Phase II clinical trial of ixabepilone in metastatic breast cancer (MBC) patients previously untreated with taxanes. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Yale Canc Ctr, New Haven, CT USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 40S EP 40S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400157 ER PT J AU Fabian, CJ Kimler, BF Anderson, JR Chamberlain, C Mayo, MS Zalles, CM O'Shaughnessy, JA Lynch, HT Johnson, KA Browne, D AF Fabian, C. J. Kimler, B. F. Anderson, J. R. Chamberlain, C. Mayo, M. S. Zalles, C. M. O'Shaughnessy, J. A. Lynch, H. T. Johnson, K. A. Browne, D. TI Phase II breast cancer chemoprevention trial of the third generation selective estrogen receptor modulator arzoxifene. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Yale Univ, New Haven, CT USA. US Oncol, Dallas, TX USA. Creighton Univ, Omaha, NE 68178 USA. NCI, Bethesda, MD 20892 USA. RI Mayo, Matthew/E-3774-2015 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 49S EP 49S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400191 ER PT J AU Arun, B Valero, V Yin, G Babiera, G Murray, JL Browne, D Gong, Y Cook, E Hortobagyi, GN Sneige, N AF Arun, B. Valero, V. Yin, G. Babiera, G. Murray, J. L. Browne, D. Gong, Y. Cook, E. Hortobagyi, G. N. Sneige, N. TI Phase II breast cancer chemoprevention study with celecoxib in women at increased risk for breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 MD Anderson Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 51S EP 51S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400201 ER PT J AU Warren, KE Draper, D Butman, JA AF Warren, K. E. Draper, D. Butman, J. A. TI Multiparametric magnetic resonance imaging (MRI) of diffuse intrinsic pontine gliomas (DIPG) after radiation therapy (XRT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 77S EP 77S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400301 ER PT J AU Ganti, AK Parr, A Nguyen, D Grem, JL AF Ganti, A. K. Parr, A. Nguyen, D. Grem, J. L. TI Gene expression profile of enzymes involved in gemcitabine (Gem) metabolism in bone marrow mononuclear cells as predictors of myelosuppression SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Nebraska, Med Ctr, Omaha, NE 68583 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 80S EP 80S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400314 ER PT J AU Takimoto, CH Liu, PY Lenz, H Remick, S Mulkerin, D Mani, S Synold, TW Ramanathan, RK Ivy, P Davies, AM AF Takimoto, C. H. Liu, P. Y. Lenz, H. Remick, S. Mulkerin, D. Mani, S. Synold, T. W. Ramanathan, R. K. Ivy, P. Davies, A. M. CA SW Oncology Grp TI A phase I pharmacokinetic (PK) study of the Epothilone B analogue, ixabepilone (BMS-247550) in patients (pts) with advanced malignancies and varying degrees of hepatic impairment. A SWOG Early Therapeutics Committee and NCI Organ Dysfunction Working Group Trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Early Therapeut Comm, SW Oncol Grp, San Antonio, TX USA. CTRC, Inst Drug Dev, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90089 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Wisconsin, Madison, WI 53706 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. City Hope Natl Med Ctr, Duarte, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NCI, Bethesda, MD 20892 USA. Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 80S EP 80S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400311 ER PT J AU Heath, EI Alousi, A Eder, JP Valdivieso, M Vasist, LS Appleman, L Bhargava, P Colevas, AD Lorusso, PM Shapiro, G AF Heath, E. I. Alousi, A. Eder, J. P. Valdivieso, M. Vasist, L. S. Appleman, L. Bhargava, P. Colevas, A. D. Lorusso, P. M. Shapiro, G. TI A phase I dose escalation trial of ispinesib (SB-715992) administered days 1-3 of a 21-day cycle in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Inst, Detroit, MI USA. GlaxoSmithKline Inc, San Francisco, CA USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 85S EP 85S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400332 ER PT J AU Mulkerin, D Remick, S Ramanathan, R Hamilton, A Takimoto, C Davies, A Ivy, P Karol, M Kolesar, J Wright, J AF Mulkerin, D. Remick, S. Ramanathan, R. Hamilton, A. Takimoto, C. Davies, A. Ivy, P. Karol, M. Kolesar, J. Wright, J. TI A dose-escalating and pharmacologic study of bortezomib in adult cancer patients with impaired renal function. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Wisconsin, NCI Organ Dysfunct Working Grp, Madison, WI 53706 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Sydney Canc Ctr, Sydney, NSW, Australia. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Natl Canc Inst, Rockville, MD USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 87S EP 87S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400339 ER PT J AU Hills, D Liebes, L Muggia, F Wright, J Pavlick, A Buckley, M Fry, D Farrell, K Hochster, H AF Hills, D. Liebes, L. Muggia, F. Wright, J. Pavlick, A. Buckley, M. Fry, D. Farrell, K. Hochster, H. TI Continuous intravenous infusion (CIVI) topotecan may be safely combined with tipifarnib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NYU, New York, NY 10012 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 95S EP 95S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400371 ER PT J AU Ramalingam, S Parise, RA Egorin, MJ Argiris, A Stoller, R Beattie, L Aparicio, A Newman, EM Zwiebel, J Belani, CP AF Ramalingam, S. Parise, R. A. Egorin, M. J. Argiris, A. Stoller, R. Beattie, L. Aparicio, A. Newman, E. M. Zwiebel, J. Belani, C. P. TI Phase I study of vorinostat, a histone deacetylase (HDAC) inhibitor, in combination with carboplatin (Cb) and paclitaxel (P) for patients with advanced solid malignancies (NCI #6922). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 98S EP 98S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400385 ER PT J AU Sportes, C Hakim, F Krumlauf, M Babb, R Fleisher, T Brown, M Engel, J Buffet, R Mackall, C Gress, R AF Sportes, C. Hakim, F. Krumlauf, M. Babb, R. Fleisher, T. Brown, M. Engel, J. Buffet, R. Mackall, C. Gress, R. TI Effects of rhIL-7 administration in humans on in vivo expansion of naive, memory and effector subsets of CD4+ & CD8+ T-cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Natl Inst Hlth, Bethesda, MD USA. Cytheris Inc, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 101S EP 101S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400393 ER PT J AU Gulley, J Arlen, PM Dahut, WL Tsang, K Jones, J Pazdur, M Jones, E Kotz, HL Schlom, J AF Gulley, J. Arlen, P. M. Dahut, W. L. Tsang, K. Jones, J. Pazdur, M. Jones, E. Kotz, H. L. Schlom, J. TI A pilot study of a PANVAC-V and PANVAC-F in patients (pts) with metastatic carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 103S EP 103S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400401 ER PT J AU Arlen, PM Gulley, JL Parker, C Skarupa, L Pazdur, M Tsang, KY Schlom, J Dahut, WL AF Arlen, P. M. Gulley, J. L. Parker, C. Skarupa, L. Pazdur, M. Tsang, K. Y. Schlom, J. Dahut, W. L. TI A randomized pilot study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen independent prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 107S EP 107S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400420 ER PT J AU Sharma, K Janik, J O'Mahony, D O'Hagan, D Gao, WW Wharfe, GH Cranston, BE Waldmann, TA Morris, JC AF Sharma, K. Janik, J. O'Mahony, D. O'Hagan, D. Gao, W. W. Wharfe, G. H. Cranston, B. E. Waldmann, T. A. Morris, J. C. TI A phase II study of the efficacy and toxicity of alemtuzumab for the therapy of human T cell lymphotrophic virus-1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Canc Inst, NIH, Bethesda, MD USA. Univ W Indies, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 108S EP 108S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400424 ER PT J AU Azad, NS Posadas, EM Kwitkowski, VE Annunziata, CM Barrett, T Premkumar, A Kotz, HL Sarosy, GA Minasian, LM Kohn, EC AF Azad, N. S. Posadas, E. M. Kwitkowski, V. E. Annunziata, C. M. Barrett, T. Premkumar, A. Kotz, H. L. Sarosy, G. A. Minasian, L. M. Kohn, E. C. TI Increased efficacy and toxicity with combination anti-VEGF therapy using sorafenib and bevacizumab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 121S EP 121S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400475 ER PT J AU Oza, AM Elit, L Biagi, J Chapman, W Tsao, M Hedley, D Hansen, C Dancey, J Eisenhauer, E AF Oza, A. M. Elit, L. Biagi, J. Chapman, W. Tsao, M. Hedley, D. Hansen, C. Dancey, J. Eisenhauer, E. TI Molecular correlates associated with a phase II study of temsirolimus (CCI-779) in patients with metastatic or recurrent endometrial cancer - NCICIND 160. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 121S EP 121S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400473 ER PT J AU Egorin, MJ Belani, CP Remick, SC Erlichman, C Teneyck, CJ Holleran, JL Ivy, SP Ramalingam, S Naret, CL Ramanathan, RK AF Egorin, M. J. Belani, C. P. Remick, S. C. Erlichman, C. Teneyck, C. J. Holleran, J. L. Ivy, S. P. Ramalingam, S. Naret, C. L. Ramanathan, R. K. TI Phase I, pharmacokinetic (PK), & pharmacodynamic (PD) study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, (17DMAG, NSC 707545) in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Case Comprehens Canc Ctr, Cleveland, OH USA. Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 126S EP 126S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400492 ER PT J AU Lyons, JA Silverman, P Remick, S Chen, H Leeming, R Shenk, R Fu, P Dumadag, L Escuro, K Overmoyer, B AF Lyons, J. A. Silverman, P. Remick, S. Chen, H. Leeming, R. Shenk, R. Fu, P. Dumadag, L. Escuro, K. Overmoyer, B. TI Toxicity results and early outcome data on a randomized phase II study of docetaxel +/- bevacizumab for locally advanced, unresectable breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Hosp Cleveland, Cleveland, OH 44106 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. US Oncol, New Milford, CT USA. NR 0 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 133S EP 133S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400520 ER PT J AU Pili, R Rudek, M Altiok, S Qian, D Zhao, M Donehower, R Anderson, A Halter, M McFarland, H Zwiebel, J Carducci, M AF Pili, R. Rudek, M. Altiok, S. Qian, D. Zhao, M. Donehower, R. Anderson, A. Halter, M. McFarland, H. Zwiebel, J. Carducci, M. TI Phase I pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor MS-275 in combination with 13-cis retinoic acid in patients with advanced solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 134S EP 134S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009400525 ER PT J AU Pierobon, M Calvert, V Lipsky, M Sheehan, K Speer, R Mammano, E Belluco, C Wulfkuhle, J Nitti, D Liotta, L Petricoin, E AF Pierobon, M. Calvert, V. Lipsky, M. Sheehan, K. Speer, R. Mammano, E. Belluco, C. Wulfkuhle, J. Nitti, D. Liotta, L. Petricoin, E., III TI Alterations in molecular networks of metastatic colorectal carcinoma reveal organ-specific signatures: Implications for targeted therapy of metastatic disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Padua, Padua, Italy. George Mason Univ, Manassas, VA USA. Univ Maryland, Baltimore, MD 21201 USA. NCI, Bethesda, MD 20892 USA. CRO Aviano Hosp, Aviano, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 3532 BP 154S EP 154S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401050 PM 27953325 ER PT J AU Land, SR Kopec, J Cecchini, R Ganz, PA Wieand, H Colangelo, L Sharif, S Kuebler, JP Costantino, J Wolmark, N AF Land, S. R. Kopec, J. Cecchini, R. Ganz, P. A. Wieand, H. Colangelo, L. Sharif, S. Kuebler, J. P. Costantino, J. Wolmark, N. TI Patient-reported neurotoxicity with FULV versus FLOX in patients with stage II or III carcinoma of the colon: Results of NSABP Protocol C-07. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Calif Los Angeles, Los Angeles, CA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. CCOP, Columbus, OH USA. NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 3564 BP 162S EP 162S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401082 PM 27953488 ER PT J AU Dahut, WL Scripture, CD Posadas, EM Wu, S Arlen, PM Gulley, JL Wright, J Chen, CC Jones, E Figg, WD AF Dahut, W. L. Scripture, C. D. Posadas, E. M. Wu, S. Arlen, P. M. Gulley, J. L. Wright, J. Chen, C. C. Jones, E. Figg, W. D. TI Bony metastatic disease responses to sorafenib (BAY 43-9006) independent of PSA in patients with metastatic androgen independent prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 218S EP 218S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401305 ER PT J AU Fossa, SD Chen, J Dores, GM McGlynn, KA Schonfeld, SJ Travis, LB AF Fossa, S. D. Chen, J. Dores, G. M. McGlynn, K. A. Schonfeld, S. J. Travis, L. B. TI Long-term non-cancer mortality among 39,657 one-year testicular cancer survivors (TCSs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Testicular Canc Res Grp, Bethesda, MD 20892 USA. Univ Oslo, Rikshosp, Radiumhosp, N-0027 Oslo, Norway. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 219S EP 219S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401308 ER PT J AU Gollob, J Richmond, T Jones, J Rathmell, WK Grigson, G Watkins, C Peterson, B Wright, J AF Gollob, J. Richmond, T. Jones, J. Rathmell, W. K. Grigson, G. Watkins, C. Peterson, B. Wright, J. TI Phase II trial of sorafenib plus interferon-alpha 2b (IFN-alpha 2b) as first- or second-line therapy in patients (pts) with metastatic renal cell cancer (RCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Invest Drug Branch, Rockville, MD USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 226S EP 226S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401336 ER PT J AU Graff, J Mori, M Li, H Garzotto, M Penson, D Potosky, A Beer, TM AF Graff, J. Mori, M. Li, H. Garzotto, M. Penson, D. Potosky, A. Beer, T. M. TI Predictors of overall and cancer-specific survival in patients with clinically localized prostate cancer (PC) treated with primary androgen deprivation therapy (PADT): Results from the Prostate Cancer Outcomes Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. Univ So Calif, Los Angeles, CA 90089 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 244S EP 244S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401408 ER PT J AU Wu, S Jones, E Gulley, J Arlen, P Chen, C Figg, W Dahut, W AF Wu, S. Jones, E. Gulley, J. Arlen, P. Chen, C. Figg, W. Dahut, W. TI Routine interval computed tomography in detecting new soft tissue disease in patients with androgen-independent prostate cancer (AIPC) and only bone metastasis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 246S EP 246S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401419 ER PT J AU Ozbun, L Bonome, T Johnson, ME Radonovich, M Pise-Masison, C Brady, J Mok, S Birrer, ME AF Ozbun, L. Bonome, T. Johnson, M. E. Radonovich, M. Pise-Masison, C. Brady, J. Mok, S. Birrer, M. E. TI Gene expression signature predicts chemoresponse of microdissected papillary serous ovarian tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 271S EP 271S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401517 ER PT J AU Blank, SV Curtin, JP Goldman, NA Runowicz, CD Speyer, JL Tiersten, AD Dancey, J Wadler, S Muggia, FM AF Blank, S. V. Curtin, J. P. Goldman, N. A. Runowicz, C. D. Speyer, J. L. Tiersten, A. D. Dancey, J. Wadler, S. Muggia, F. M. TI Report of first-stage accrual for NCI 5886, a phase II study of erlotinib, carboplatin and paclitaxel as first-line treatment of ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NYU, Sch Med, New York Gynecol Oncol Grp, New York, NY 10012 USA. Univ Connecticut, Farmington, CT 06032 USA. NCI, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 274S EP 274S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401529 ER PT J AU Welch, S Hirte, H Schilder, RJ Elit, L Townsley, C Tinker, L Pond, G Afinec, A Wright, JJ Oza, AM AF Welch, S. Hirte, H. Schilder, R. J. Elit, L. Townsley, C. Tinker, L. Pond, G. Afinec, A. Wright, J. J. Oza, A. M. TI Phase II study of sorafenib (BAY 43-9006) in combination with gemcitabine in recurrent epithelial ovarian cancer: A PMH phase II consortium trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Princess Margaret Hosp Phase II Consortium, Toronto, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 276S EP 276S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009401537 ER PT J AU Seiwert, TY Haraf, DJ Cohen, EE Stenson, K Mauer, AM Dekker, A Bajda, C Weichselbaum, RR Chen, HX Vokes, EE AF Seiwert, T. Y. Haraf, D. J. Cohen, E. E. Stenson, K. Mauer, A. M. Dekker, A. Bajda, C. Weichselbaum, R. R. Chen, H. X. Vokes, E. E. TI A phase I study of bevacizumab (B) with fluorouracil (F) and hydroxyurea (H) with concomitant radiotherapy (X) (B-FHX) for poor prognosis head and neck cancer (HNC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 287S EP 287S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402018 ER PT J AU Agulnik, M Cohen, EE Cohen, RB Chen, EX Hotte, SJ Winquist, E Laurie, S Hayes, DN Dancey, JE Siu, LL AF Agulnik, M. Cohen, E. E. Cohen, R. B. Chen, E. X. Hotte, S. J. Winquist, E. Laurie, S. Hayes, D. N. Dancey, J. E. Siu, L. L. TI A phase II study of lapatinib in recurrent or metastatic EGFR and/or ErbB2 expressing adenoid cystic (ACC) and non-ACC malignant tumors of the salivary glands (MSGT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Princess Margaret Hosp Phase II Consortium, Toronto, ON, Canada. Univ Chicago, Phase Consortium 2, Chicago, IL 60637 USA. Univ N Carolina, Chapel Hill, NC USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 296S EP 296S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402054 ER PT J AU Abidoye, OO Cohen, EE Wong, SJ Kozloff, MF Nattam, SR Stenson, KM Blair, EA Day, S Dancey, JE Vokes, EE AF Abidoye, O. O. Cohen, E. E. Wong, S. J. Kozloff, M. F. Nattam, S. R. Stenson, K. M. Blair, E. A. Day, S. Dancey, J. E. Vokes, E. E. TI A phase II study of lapatinib (GW572016) in recurrent/metastatic (RIM) squamous cell carcinoma of the head and neck (SCCHN). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Chicago Hosp, Chicago, IL 60637 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Ingalls Canc Care Ctr, Harvey, IL USA. Ft Wayne Oncol & Hematol, Ft Wayne, IN USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 297S EP 297S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402057 ER PT J AU Argiris, A Goldwasser, MA Burtness, B Deconti, R Axelrod, R Van Waes, C Forastiere, A AF Argiris, A. Goldwasser, M. A. Burtness, B. Deconti, R. Axelrod, R. Van Waes, C. Forastiere, A. TI A phase II trial of PS-341 (bortezomib) followed by the addition of doxorubicin at progression in incurable adenoid cystic carcinoma of the head and neck: An Eastern Cooperative Oncology Group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Natl Canc Inst, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 298S EP 298S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402063 ER PT J AU Garcia, R Freund, KM Dudley, D Fiscella, K Jones, JD Patierno, SR Raich, PC Roetzheim, RG Paskett, E Bennett, CL AF Garcia, R. Freund, K. M. Dudley, D. Fiscella, K. Jones, J. D. Patierno, S. R. Raich, P. C. Roetzheim, R. G. Paskett, E. Bennett, C. L. TI Extending the patient navigator research program from Harlem to the nation. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Rochester, Sch Med & Dent, Rochester, NY 14627 USA. NW Portland Area Indian Hlth Board, Portland, OR USA. George Washington Univ, Inst Canc, Washington, DC USA. Denver Hlth & Hosp Author, Denver, CO USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. Ohio State Univ, Columbus, OH 43210 USA. Northwestern Univ, Chicago, IL 60611 USA. RI Roetzheim, Richard/J-4696-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 6096 BP 324S EP 324S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402166 PM 27954777 ER PT J AU Davidson, B Vogel, V Wickerham, L AF Davidson, B. Vogel, V. Wickerham, L. TI How conversations about adjuvant hormonal therapy differ from 'typical' oncology discussions: Results of an observational linguistic study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NSABP, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 335S EP 335S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402212 ER PT J AU Byrd, JC Lin, TS Dalton, JT Phelps, M Fischer, B Moran, M Blum, K Rovin, B Colevas, AD Grever, MR AF Byrd, J. C. Lin, T. S. Dalton, J. T. Phelps, M. Fischer, B. Moran, M. Blum, K. Rovin, B. Colevas, A. D. Grever, M. R. TI Pharmacologically derived schedule of flavopiridol has significant efficacy in refractory, genetically high risk chronic lymphocytic leukemia (CLL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. RI Phelps, Mitch/H-3941-2013; Blum, Kristie/E-2768-2011 OI Phelps, Mitch/0000-0002-1615-5280; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 341S EP 341S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402233 ER PT J AU Dean, RM Fowler, DH Steinberg, SM Odom, J Gea-Banacloche, J Sportes, C Hardy, N Pavletic, S Gress, RE Bishop, MR AF Dean, R. M. Fowler, D. H. Steinberg, S. M. Odom, J. Gea-Banacloche, J. Sportes, C. Hardy, N. Pavletic, S. Gress, R. E. Bishop, M. R. TI Targeted immune depletion prior to reduced-intensity allogeneic stem cell transplantation results in rapid and complete donor chimerism with low treatment-related mortality. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 347S EP 347S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402257 ER PT J AU Bishop, MR Dean, RM Steinberg, S Odom, J Pavletic, SZ Kasten-Sportes, C Hardy, N Pittaluga, S Gress, R Fowler, DH AF Bishop, M. R. Dean, R. M. Steinberg, S. Odom, J. Pavletic, S. Z. Kasten-Sportes, C. Hardy, N. Pittaluga, S. Gress, R. Fowler, D. H. TI Reduced-intensity allogeneic stem cell transplantation for diffuse large B-cell lymphoma: Clinical evidence of a graft-versus-lymphoma effect. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 348S EP 348S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402262 ER PT J AU Mansueti, JR Singh, AK Karimpour, SE Guion, P Ning, H Savani, B Wu, C Altemus, R Barrett, J AF Mansueti, J. R. Singh, A. K. Karimpour, S. E. Guion, P. Ning, H. Savani, B. Wu, C. Altemus, R. Barrett, J. TI Pretreatment pulmonary function tests predict risk of mortality following fractionated total body irradiation without lung dose reduction prior to stem cell transplant. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 349S EP 349S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402266 ER PT J AU Ravandi-Kashani, F Kantarjian, H Garcia-Manero, G O'Brien, S Verstovsek, S Estrov, Z Faderl, S Giles, F Wright, J Cortes, J AF Ravandi-Kashani, F. Kantarjian, H. Garcia-Manero, G. O'Brien, S. Verstovsek, S. Estrov, Z. Faderl, S. Giles, F. Wright, J. Cortes, J. TI Tipifarnib in combination with idarubicin and cytarabine in patients with newly diagnosed acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Invest Drug Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 351S EP 351S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402275 ER PT J AU Blum, W Klisovic, RB Kefauver, C Johnson, A Phelps, M Dalton, JT Lucas, D Colevas, AD Grever, MR Marcucci, G Byrd, JC AF Blum, W. Klisovic, R. B. Kefauver, C. Johnson, A. Phelps, M. Dalton, J. T. Lucas, D. Colevas, A. D. Grever, M. R. Marcucci, G. Byrd, J. C. TI Phase I study of a novel, pharmacokinetically derived schedule of flavopiridol in acute leukemias: Clinical efficacy including hyperacute tumor lysis, pharmacokinetics, and pharmacodynamics. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. RI Phelps, Mitch/H-3941-2013; Blum, William/E-2769-2011 OI Phelps, Mitch/0000-0002-1615-5280; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 353S EP 353S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009402284 ER PT J AU Chen, CI Kouroukis, T White, D Voralia, M Stadtmauer, E Wright, J Powers, J Eisenhauer, E AF Chen, C. I. Kouroukis, T. White, D. Voralia, M. Stadtmauer, E. Wright, J. Powers, J. Eisenhauer, E. TI Bortezomib is active in Waldenstrom's Macroglobulinemia (WM) - Results of a National Cancer Institute of Canada (NCIC) phase II study in previously untreated or treated WM. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada. Saskatoon Canc Ctr, Saskatoon, SK, Canada. Eastern Cooperat Oncol Grp, Philadelphia, PA USA. NIH, Bethesda, MD USA. Netaji Subhash Chandra Bose Canc Res Inst, Kingston, ON, Canada. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 432S EP 432S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403032 ER PT J AU Gause, BL Neelapu, SS Cohen, CM Katz, LM Watson, T Stergiou, AM Kwak, LW AF Gause, B. L. Neelapu, S. S. Cohen, C. M. Katz, L. M. Watson, T. Stergiou, A. M. Kwak, L. W. TI Idiotype vaccine therapy of follicular lymphoma in first remission: Association of t(14;18) and disease free survival in a phase II cohort. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Biovest Int, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 442S EP 442S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403070 ER PT J AU Lin, TS Fischer, B Moran, ME Shank, RS Kraut, E Porcu, P Farag, SS Blum, KA Colevas, AD Grever, MR Byrd, JC AF Lin, T. S. Fischer, B. Moran, M. E. Shank, R. S. Kraut, E. Porcu, P. Farag, S. S. Blum, K. A. Colevas, A. D. Grever, M. R. Byrd, J. C. TI Flavopiridol, fludarabine and rituximab (FFR) is an active regimen in indolent B-cell lymphoproliferative disorders and mantle cell lymphoma (MCL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. Natl Canc Inst, Bethesda, MD USA. RI Blum, Kristie/E-2768-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 446S EP 446S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403087 ER PT J AU Farag, SS Zhang, S Miller, M Buckner, M Kraut, E Chan, K Eng, C Byrd, JC Dancey, JE Grever, MR AF Farag, S. S. Zhang, S. Miller, M. Buckner, M. Kraut, E. Chan, K. Eng, C. Byrd, J. C. Dancey, J. E. Grever, M. R. TI Phase II trial of temsirolimus (CCI-779) in patients with relapsed or refractory multiple myeloma (MM): Preliminary results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Ohio State Univ, Columbus, OH 43210 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NIH, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 450S EP 450S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403103 ER PT J AU Soriano, PA Libutti, SK Pingpank, JF Beresenev, T Steinberg, SM Bartlett, DL Fraker, DL Helsabeck, C Alexander, HR AF Soriano, P. A. Libutti, S. K. Pingpank, J. F. Beresenev, T. Steinberg, S. M. Bartlett, D. L. Fraker, D. L. Helsabeck, C. Alexander, H. R., Jr. TI Analysis of factors influencing outcome in patients with in transit malignant melanoma (MM) undergoing isolated limb perfusion (ILP) using standardized operative parameters with melphalan and biological agents. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 454S EP 454S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403118 ER PT J AU Hardin, E Pavlick, AC Liebes, L Osman, I Hamilton, A Soon, J Polsky, D Friedman, K Wright, J Muggia, F AF Hardin, E. Pavlick, A. C. Liebes, L. Osman, I. Hamilton, A. Soon, J. Polsky, D. Friedman, K. Wright, J. Muggia, F. TI A phase II trial of BAY 43-9006 in metastatic melanoma with molecularly characterized B-Raf status. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NYU, Inst Canc, New York, NY USA. Sydney Canc Ctr, Sydney, NSW, Australia. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 8046 BP 464S EP 464S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403157 PM 27955485 ER PT J AU Demark-Wahnefried, W Clipp, E Lipkus, I Lobach, D Peterson, B Snyder, D Sloane, R Macri, J McBride, C Kraus, W AF Demark-Wahnefried, W. Clipp, E. Lipkus, I. Lobach, D. Peterson, B. Snyder, D. Sloane, R. Macri, J. McBride, C. Kraus, W. TI Results of FRESH START: A randomized controlled trial to improve diet and exercise behaviors in breast and prostate cancer survivors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Duke Univ, Med Ctr, Durham, NC USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 8503 BP 468S EP 468S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403175 PM 27954194 ER PT J AU Goldsby, R Burke, C Nagarajan, R Zhou, T Chen, Z Inskip, P Marina, N Friedman, D Neglia, J Bhatia, S AF Goldsby, R. Burke, C. Nagarajan, R. Zhou, T. Chen, Z. Inskip, P. Marina, N. Friedman, D. Neglia, J. Bhatia, S. TI Solid organ second malignant neoplasms among children diagnosed with malignant bone tumors treated on Children Cancer Study Group/Pediatric Oncology Group protocols after 1980. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Childrens Oncol Grp, Arcadia, CA USA. Natl Canc Inst, Bethesda, MD USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9007 BP 503S EP 503S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403312 PM 27954220 ER PT J AU Kim, SY Cohen, SA Epps, J Smedley, J Mendoza, A Khanna, C Jones, B Aziz, N Helman, LJ AF Kim, S. Y. Cohen, S. A. Epps, J. Smedley, J. Mendoza, A. Khanna, C. Jones, B. Aziz, N. Helman, L. J. TI Reduction of murine osteosarcoma lung metastases using the dipeptidyl peptidase inhibitor talabostat. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Inst Hlth, Bethesda, MD USA. Point Therapeut Corp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9009 BP 504S EP 504S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403314 PM 27954218 ER PT J AU Bradley, K Mehta, M Adamson, P Ames, M Jakacki, R Vezina, G Ingle, A Ivy, P Blaney, S Pollack, I AF Bradley, K. Mehta, M. Adamson, P. Ames, M. Jakacki, R. Vezina, G. Ingle, A. Ivy, P. Blaney, S. Pollack, I. TI Phase I study of concurrent motexafin gadolinium (MGd) with radiation therapy for children with newly diagnosed brain stem gliomas (BSG): A Children's Oncology Group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Wisconsin, Madison, WI USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Oncol Grp, Arcadia, CA USA. Natl Canc Inst, Bethesda, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9014 BP 505S EP 505S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403319 PM 27954206 ER PT J AU Jakacki, RI Tersak, J Blaney, S Krailo, M Hamilton, M Dancy, J Gilbertson, R Ingle, A Adamson, PC AF Jakacki, R. I. Tersak, J. Blaney, S. Krailo, M. Hamilton, M. Dancy, J. Gilbertson, R. Ingle, A. Adamson, P. C. TI A pediatric phase I trial and pharmacokinetic (PK) study of erlotinib (ERL) followed by the combination of ERL with temozolomide (TMZ): A Children's Oncology Group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Texas Childrens Canc Ctr, Houston, TX USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. OSI Pharmaceut, Boulder, CO USA. Natl Canc Inst, Washington, DC USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Oncol Grp, Arcadia, CA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN 20 PY 2006 VL 24 IS 18 SU S MA 9015 BP 505S EP 505S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403320 PM 27954200 ER PT J AU Bender, JLG Adamson, PC Baruchel, S Shaked, Y Chen, HX Reid, JM Ingle, AM Blaney, SM Kandel, JJ Yamashiro, DJ AF Bender, J. L. Glade Adamson, P. C. Baruchel, S. Shaked, Y. Chen, H. X. Reid, J. M. Ingle, A. M. Blaney, S. M. Kandel, J. J. Yamashiro, D. J. TI Phase I study of bevacizumab in children with refractory solid tumors: A Children's Oncology Group study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Columbia Univ, New York, NY USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Sunnybrook & Womens Hlth Sci Ctr, Toronto, ON M5G 1X8, Canada. Natl Canc Inst, Bethesda, MD USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Childrens Oncol Grp, Arcadia, CA USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9017 BP 506S EP 506S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403322 ER PT J AU Weigel, B Blaney, S Kersey, J Bagatell, R Ivy, SP Whitesell, L Krailo, M Reid, J Ames, M Adamson, P AF Weigel, B. Blaney, S. Kersey, J. Bagatell, R. Ivy, S. P. Whitesell, L. Krailo, M. Reid, J. Ames, M. Adamson, P. TI A phase I study of 17-AAG in relapsed/refractory pediatric patients with solid tumors: A Children's Oncology Groups study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Minnesota, Minneapolis, MN USA. Baylor Univ, Houston, TX 77030 USA. Univ Arizona, Tucson, AZ USA. Natl Canc Inst, Washington, DC USA. Whitehead Inst, Cambridge, ME USA. Childrens Oncol Grp, Arcadia, CA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9018 BP 506S EP 506S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403323 PM 27954240 ER PT J AU Fox, E Jayaprakash, N Widemann, BC Hawkins, D Dagher, R Mansky, P Mackall, C Helman, LJ Steinberg, S Balis, FM AF Fox, E. Jayaprakash, N. Widemann, B. C. Hawkins, D. Dagher, R. Mansky, P. Mackall, C. Helman, L. J. Steinberg, S. Balis, F. M. TI Randomized trial and pharmacokinetic study of pegfilgrastim vs. filgrastim in children and young adults with newly diagnosed sarcoma treated with dose intensive chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9020 BP 507S EP 507S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403325 PM 27954233 ER PT J AU Hoffman, KE Derdak, J Bernstein, D Reynolds, JC Steinberg, SM Chrousos, G Gerber, L Mackall, CL Mansky, PJ AF Hoffman, K. E. Derdak, J. Bernstein, D. Reynolds, J. C. Steinberg, S. M. Chrousos, G. Gerber, L. Mackall, C. L. Mansky, P. J. TI Metabolic syndrome traits in long-term survivors of pediatric sarcoma at a single institution. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Natl Inst Hlth, Ctr Clin, Bethesda, MD USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9041 BP 512S EP 512S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403345 PM 27954444 ER PT J AU Albritton, KH Rankin, C Coffin, CM Ratner, N Budd, GT Schuetze, SM Randall, RL Declue, JE Borden, EC AF Albritton, K. H. Rankin, C. Coffin, C. M. Ratner, N. Budd, G. T. Schuetze, S. M. Randall, R. L. Declue, J. E. Borden, E. C. TI Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. SW Oncol Grp, San Antonio, TX 78229 USA. Univ Utah, Salt Lake City, UT USA. Childrens Hosp, Cincinnati, OH 45229 USA. Cleveland Clin, Cleveland, OH 44106 USA. Natl Canc Inst, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 9518 BP 524S EP 524S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403391 PM 27952832 ER PT J AU Bertagnolli, MM Compton, CC Niedzwiecki, D Warren, RS Jewell, S Bailey, GP Mayer, RJ Goldberg, R Saltz, L Redston, M AF Bertagnolli, M. M. Compton, C. C. Niedzwiecki, D. Warren, R. S. Jewell, S. Bailey, G. P. Mayer, R. J. Goldberg, R. Saltz, L. Redston, M. TI Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, 5-fluorouracil and leucovorin in stage III colon cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Canc & Leukemia Grp B, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Ohio State Univ, Columbus, OH 43210 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 10003 BP 541S EP 541S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403459 PM 27955350 ER PT J AU Speer, R Wallwiener, D Yang, SX Swain, SM Wulfkuhle, JD Liotta, LA Petricoin, EF AF Speer, R. Wallwiener, D. Yang, S. X. Swain, S. M. Wulfkuhle, J. D. Liotta, L. A. Petricoin, E. F. TI Molecular network analysis of signaling pathways in metastatic breast cancer in patients treated with erlotinib. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Univ Tubingen, Tubingen, Germany. NCI, Bethesda, MD 20892 USA. George Mason Univ, Manassas, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 10064 BP 556S EP 556S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403518 PM 27954175 ER PT J AU Varticovski, L Hollingshead, G Anver, R Robles, AI Green, JE Hunter, W Merlino, G Nunez, N Hursting, SD Steeg, PS Barrett, CJ AF Varticovski, L. Hollingshead, M. G. Anver, M. R. Robles, A. I. Green, J. E. Hunter, K. W. Merlino, G. Nunez, N. Hursting, S. D. Steeg, P. S. Barrett, C. J. TI Preclinical testing using tumors from genetically engineered mouse mammary models. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. Univ Texas, Austin, TX 78712 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S MA 10067 BP 557S EP 557S PN 1 PG 1 WC Oncology SC Oncology GA 063HN UT WOS:000239009403521 PM 27954176 ER PT J AU Wickerham, DL Costantino, JP Vogel, V Cronin, W Cecchini, R Atkins, J Bevers, T Fehrenbacher, L McCaskill-Stevens, W Wolmark, N AF Wickerham, D. L. Costantino, J. P. Vogel, V. Cronin, W. Cecchini, R. Atkins, J. Bevers, T. Fehrenbacher, L. McCaskill-Stevens, W. Wolmark, N. TI The study of tamoxifen and raloxifene (STAR): Initial findings from the NSABP P-2 breast cancer prevention study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. SE Canc Control Consortium Inc, Winston Salem, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Kaiser Permanente, Vallejo, CA USA. NCI, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2006 VL 24 IS 18 SU S BP 930S EP 930S PN 2 PG 1 WC Oncology SC Oncology GA 063HQ UT WOS:000239009700003 ER PT J AU Boissinot, S Davis, J Entezam, A Petrov, D Furano, AV AF Boissinot, Stephane Davis, Jerel Entezam, Ali Petrov, Dimitri Furano, Anthony V. TI Fitness cost of LINE-1 (L1) activity in humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetics; retrotransposon ID TRANSPOSABLE ELEMENTS; DROSOPHILA-MELANOGASTER; ECTOPIC RECOMBINATION; EVOLUTIONARY DYNAMICS; HUMAN GENOME; RETROTRANSPOSONS; POPULATION; LINEAGE; HISTORY; SIZE AB The self-replicating LINE-1 (L1) retrotransposon family is the dominant retrotransposon family in mammals and has generated 30-40% of their genomes. Active L1 families are present in modern mammals but the important question of whether these currently active families affect the genetic fitness of their hosts has not been addressed. This issue is of particular relevance to humans as Homo sapiens contains the active L1 Tal1 subfamily of the human specific Ta (L1Pa1) L1 family. Although DNA insertions generated by the Tall subfamily can cause genetic defects in current humans, these are relatively rare, and it is not known whether Ta1-generated inserts or any other property of Ta1 elements have been sufficiently deleterious to reduce the fitness of humans. Here we show that full-length (FL) Ta1 elements, but not the truncated Ta1 elements or SINE (Alu) insertions generated by Ta1 activity, were subject to negative selection. Thus, one or more properties unique to FL L1 elements constitute a genetic burden for modern humans. We also found that the FL Ta1 elements became more deleterious as the expansion of Ta1 has proceeded. Because this expansion is ongoing, the Ta1 subfamily almost certainly continues to decrease the fitness of modern humans. C1 NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bethesda, MD 20892 USA. CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA. Stanford Univ, Dept Sci Biol, Stanford, CA 94305 USA. RP Furano, AV (reprint author), NIDDKD, Mol & Cellular Biol Lab, Sect Genom Struct & Funct, NIH, Bldg 8,Room 203,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM avf@helix.nih.gov FU Intramural NIH HHS NR 28 TC 58 Z9 58 U1 2 U2 5 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 JUN 20 PY 2006 VL 103 IS 25 BP 9590 EP 9594 DI 10.1073/pnas.0603334103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 058JD UT WOS:000238660400038 PM 16766655 ER PT J AU Ho, M Nagata, S Pastan, I AF Ho, M Nagata, S Pastan, I TI Isolation of anti-CD22 Fv with high affinity by Fv display on human cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibody engineering; B cell malignancy; FACS; human embryonic kidney cells; receptors ID MIMICKING SOMATIC HYPERMUTATION; ANTIBODY PHAGE DISPLAY; GROWTH-FACTOR RECEPTOR; YEAST SURFACE DISPLAY; IN-VITRO SELECTION; RIBOSOME DISPLAY; DIRECTED EVOLUTION; CYTOTOXIC ACTIVITY; ESCHERICHIA-COLI; EXTERNAL SURFACE AB in vitro antibody affinity maturation has generally been achieved by display of mouse or human antibodies on the surface of microorganisms (phage, bacteria, and yeast). However, problems with protein folding, posttranslational modification, and codon usage still limit the number of improved antibodies that can be obtained. An ideal system would select and improve antibodies in a mammalian cell environment where they are naturally made. Here we show that human embryonic kidney 293T cells that are widely used for transient protein expression can be used for cell surface display of single-chain Fv antibodies for affinity maturation. In a proof-of-concept experiment, cells expressing a rare mutant antibody with higher affinity were enriched 240-fold by a single-pass cell sorting from a large excess of cells expressing WT antibody with a slightly lower affinity. Furthermore, we successfully obtained a highly enriched mutant with increased binding affinity for CD22 after a single selection of a combinatory library randomizing an intrinsic antibody hotspot. Important features are that one display selection cycle requires only 1 week, and transfection of cells in a single 100-mm dish produces 10(7) individual clones so that a repertoire of 10(9) is feasible under current experimental conditions. C1 NCI, Ctr Canc Res, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Ctr Canc Res, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Ho, Mitchell/F-5059-2015 FU Intramural NIH HHS NR 46 TC 69 Z9 76 U1 0 U2 17 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 JUN 20 PY 2006 VL 103 IS 25 BP 9637 EP 9642 DI 10.1073/pnas.0603653103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 058JD UT WOS:000238660400046 PM 16763048 ER PT J AU Wang, SX Pal, R Mascola, JR Chou, THW Mboudjeka, I Shen, SY Liu, Q Whitney, S Keen, T Nair, BC Kalyanaraman, VS Markham, P Lu, S AF Wang, SX Pal, R Mascola, JR Chou, THW Mboudjeka, I Shen, SY Liu, Q Whitney, S Keen, T Nair, BC Kalyanaraman, VS Markham, P Lu, S TI Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus protein boosting approach are effective in generating neutralizing antibodies against primary human immunodeficiency virus type 1 isolates from subtypes A, B, C, D and E SO VIROLOGY LA English DT Article DE HIV vaccine; envelope glycoprotein; neutralizing antibody; polyvalent vaccine ID RECOMBINANT GLYCOPROTEIN-120 VACCINE; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; PASSIVE TRANSFER; STERILIZING PROTECTION; INFECTED SUBJECTS; IMMUNE-RESPONSES; SHIV INFECTION; CHIMERIC VIRUS; GP120 PROTEIN AB A major challenge in developing an HIV-1 vaccine is to identify immunogens and their delivery methods that can elicit broad neutralizing antibodies against primary isolates of different genetic subtypes. Recently, we demonstrated that priming with DNA vaccines expressing primary HIV-1 envelope glycoprotein (Env) followed by recombinant Env protein boosting was successful in generating positive neutralizing antibody responses against a clade B primary HIV-1 isolate, JR-FL, that was not easily neutralized. In the current study, we examined whether the DNA priming plus recombinant protein boosting approach delivering a polyvalent primary Env formulation was able to generate neutralizing antibodies against primary HIV-1 viral isolates from various genetic subtypes. New Zealand White rabbits were first immunized with DNA vaccines expressing one, three or eight primary HIV-1 gp120 antigens delivered by a gene gun followed by recombinant gp120 protein boosting. Neutralizing antibody responses were examined by two independently executed neutralization assays: the first one was a single round infection neutralization assay against a panel of 10 primary HIV-1 isolates of subtypes A, 13, C and E and the second one used the PhenoSense assay against a panel of 12 pseudovirues expressing primary HIV-1 Env antigens from subtypes A, B, C, D and E as well as 2 pseudoviruses expressing the Env antigens from MN and NL4-3 viruses. Rabbit sera immunized with the DNA priming plus protein boosting approach, but not DNA vaccine alone or Env protein alone, were capable of neutralizing 7 of 10 viruses in the first assay and 12 of 14 viruses in the second assay. More importantly, sera immunized with the polyvalent Env antigens were able to neutralize a significantly higher percentage of viruses than the sera immunized with the monovalent antigens. Our results suggest that DNA priming followed by recombinant Env protein boosting can be used to deliver polyvalent Env-antigen-based HIV-1 vaccines to elicit neutralizing antibody responses against viruses with diverse genetic sequence variations. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, Worcester, MA 01605 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01655 USA. RP Lu, S (reprint author), Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, 364 Plantat St,Lazare Res Bldg, Worcester, MA 01605 USA. EM shan.lu@umassmed.edu OI Lu, Shan/0000-0002-8417-7588 FU Intramural NIH HHS; NIAID NIH HHS [R01AI40337, R21AI46294, U01AI05394] NR 74 TC 72 Z9 73 U1 1 U2 6 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 JUN 20 PY 2006 VL 350 IS 1 BP 34 EP 47 DI 10.1016/j.virol.2006.02.032 PG 14 WC Virology SC Virology GA 056YV UT WOS:000238561900004 PM 16616287 ER PT J AU Inbaraj, JJ Kukielczak, BM Bilski, P He, YY Sik, RH Chignell, CF AF Inbaraj, J. J. Kukielczak, B. M. Bilski, P. He, Y. -Y. Sik, R. H. Chignell, C. F. TI Photochemistry and photocytotoxicity of alkaloids from goldenseal (Hydrastis canadensis L.). 2. Palmatine, hydrastine, canadine, and hydrastinine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 5,5-DIMETHYL-1-PYRROLINE N-OXIDE; SINGLET OXYGEN; AQUEOUS-SOLUTION; ROOT POWDER; BERBERINE; DNA; QUANTITATION; SUPEROXIDE; GENERATION; DAMAGE AB Goldenseal is an herb that is widely used in dietary supplements, eye washes, and skin lotions. The presence of Goldenseal root powder in dietary supplements and the topical application of Goldenseal preparations raise the possibility that an adverse phototoxic reaction may result from an interaction between its constituent alkaloids and light in exposed tissues. We have previously shown that berberine, the major alkaloid in Goldenseal powder, in combination with UVA causes DNA damage and cell death in HaCaT keratinocytes [(2001) Chem. Res. Toxicol. 14, 1529]. We have studied the photochemical and photobiological properties of four minor alkaloids found in Goldenseal, namely, hydrastine, palmatine, canadine, and hydrastinine. UVA radiation of palmatine in aqueous solutions generated no (1)O(2), but in CH(2)Cl(2), copious amounts of (1)O(2) were detected (Phi = 0.2). Palmatine also photogenerated oxygen-centered radicals, (center dot)OH and O(2)(center dot-) in aerated aqueous buffer and acetonitrile, respectively, as detected by the spin trap 5,5-dimethyl-1-pyrrolineN-oxide (DMPO). In nitrogen-sparged acetonitrile containing DMPO, we observed the neutral palmatine radical formed by one-electron reduction. UVA irradiation (4 J/cm(2)) of HaCaT keratinocytes in the presence of palmatine (50 mu M) resulted in a 50% decrease in cell viability but no DNA damage as measured by the comet assay. UVA irradiation of hydrastine, hydrastinine, or canadine (50 mu M) did not cause DNA damage or cell death in keratinocytes. Although palmatine is photoactive, it is present in such small amounts in Goldenseal root powder that the phototoxicity of the herb is most likely due to berberine, the major constituent alkaloid. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Inbaraj, JJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS NR 24 TC 12 Z9 12 U1 2 U2 6 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 JUN 19 PY 2006 VL 19 IS 6 BP 739 EP 744 DI 10.1021/tx050356u PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 053RR UT WOS:000238323200003 PM 16780351 ER PT J AU Giri, S Idle, JR Chen, C Zabriskie, TM Krausz, KW Gonzalez, FJ AF Giri, S Idle, JR Chen, C Zabriskie, TM Krausz, KW Gonzalez, FJ TI A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID BETEL QUID CARCINOGENESIS; L-PIPECOLIC ACID; THIOESTER REDUCTASE; N-OXIDE; RESOLUTION; LYSINE; RAT AB The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine. Approximately 600 million users of areca nut products, for example, betel quid chewers, are exposed to these alkaloids, principally arecoline and arecaidine. Metabolism of arecoline (20 mg/kg p.o. and i.p.) and arecaidine (20 mg/kg p.o. and i.p.) was investigated in the mouse using a metabolomic approach employing ultra-performance liquid chromatography-time-of-flight mass spectrometric analysis of urines. Eleven metabolites of arecoline were identified, including arecaidine, arecoline N-oxide, arecaidine N-oxide, N-methylnipecotic acid, N-methylnipecotylglycine, arecaidinylglycine, arecaidinylglycerol, arecaidine mercapturic acid, arecoline mercapturic acid, and arecoline N-oxide mercapturic acid, together with nine unidentified metabolites. Arecaidine shared six of these metabolites with arecoline. Unchanged arecoline comprised 0.3-0.4%, arecaidine 7.1-13.1%, arecoline N-oxide 7.4-19.0%, and N-methylnipecotic acid 13.5-30.3% of the dose excreted in 0-12 h urine after arecoline administration. Unchanged arecaidine comprised 15.1-23.0%, and N-methylnipecotic acid 14.8%-37.7% of the dose excreted in 0-12 h urine after arecaidine administration. The major metabolite of both arecoline and arecaidine, N-methylnipecotic acid, is a novel metabolite arising from carbon-carbon double-bond reduction. Another unusual metabolite found was the monoacylglyceride of arecaidine. What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known. However, the enhanced understanding of the metabolic transformation of arecoline and arecaidine should contribute to further research into the clinical toxicology of the areca alkaloids. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Charles Univ, Inst Pharmacol, Fac Med 1, Prague 12800 2, Czech Republic. Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nil.gov RI Chen, Chi/B-4618-2008; OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005562-18] NR 27 TC 57 Z9 58 U1 2 U2 16 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 JUN 19 PY 2006 VL 19 IS 6 BP 818 EP 827 DI 10.1021/tx0600402 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 053RR UT WOS:000238323200013 PM 16780361 ER PT J AU Lisinski, I Matsumoto, H Yver, DR Schurmann, A Cushman, SW Al-Hasani, H AF Lisinski, I Matsumoto, H Yver, DR Schurmann, A Cushman, SW Al-Hasani, H TI Identification and characterization of p49/STRAP as a novel GLUT4-binding protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE GLUT4; adipose cells; protein biosynthesis; yeast two-hybrid system ID GLUCOSE-TRANSPORTER GLUT4; INTERACTS; ENDOCYTOSIS; CLONING; YEAST; USO1P; P115; ER AB To identify novel regulatory components involved in the recycling of the insulin-responsive glucose transporter GLUT4, we have used the yeast two-hybrid system to isolate GLUT4-binding proteins from a rat adipose cell cDNA library. We found a 49-kDa protein (p49/STRAP) that specifically interacts with an acidic amino acid motif (Q(7)IGSEDG) in the N-terminus of GLUT4. Confocal immunofluorescence microscopy of primary rat adipose cells shows co-localization of myc-p49 with GLUT4 and also with the ER-resident protein calnexin. Insulin stimulation had no effect on GLUT4-binding and subcellular distribution of p49 in adipose cells. However, overexpression of the GLUT4-binding domain of p49 in adipose cells reduces protein synthesis and cell-surface expression of GLUT4, but not of GLUT8. Moreover, cell-surface expression of a p49-binding-deficient GLUT4 mutant (ED/QN) is also reduced. Kinetic analysis of HA-epitope-tagged GLUT4 protein synthesis indicates a possible role of p49 in biosynthesis and/or processing of GLUT4 in adipose cells. (c) 2006 Elsevier Inc. All rights reserved. C1 German Inst Human Nutr, Potsdam, Germany. NIDDK, EDMNS, DB, NIH, Bethesda, MD USA. RP Al-Hasani, H (reprint author), German Inst Human Nutr, Potsdam, Germany. EM al-hasani@mail.dife.de OI Schurmann, Annette/0000-0002-4113-4377 NR 17 TC 5 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 16 PY 2006 VL 344 IS 4 BP 1179 EP 1185 DI 10.1016/j.bbrc.2006.04.017 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 044NL UT WOS:000237679200018 PM 16647043 ER PT J AU Sugawara, E Nestorovich, EM Bezrukov, SM Nikaido, H AF Sugawara, E Nestorovich, EM Bezrukov, SM Nikaido, H TI Pseudomonas aeruginosa porin OprF exists in two different conformations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE PROTEIN OPRF; BACTERIAL-CELL-SURFACE; GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE; ESCHERICHIA-COLI; OMPA PROTEIN; SYNTHETIC PEPTIDES; GROWTH TEMPERATURE; DIFFUSION PORES; MOLECULAR-BASIS AB The major nonspecific porin of Pseudomonas aeruginosa, OprF, produces a large channel yet allows only a slow diffusion of various solutes. Here we provide an explanation of this apparent paradox. We first show, by introduction of tobacco etch virus protease cleavage site in the middle of OprF protein, that most of OprF population folds as a two-domain protein with an N-terminal beta-barrel domain and a C-terminal periplasmic domain rich in alpha-helices. However, sedimentation of unilamellar proteoliposomes through an iso-osmotic gradient showed that only about 5% of the OprF population produced open channels. Gel filtration showed that the open channel conformers tended to occur in oligomeric associations. Because the open channel conformer is likely to fold as a single domain protein with a large beta-barrel, we reasoned that residues near the C terminus may be exposed on cell surface in this conformer. Introduction of a cysteine residue at position 312 produced a functional mutant protein. By using bulky biotinylation reagents on intact cells, we showed that this cysteine residue was not exposed on cell surface in most of the OprF population. However, the minority OprF population that was biotinylated in such experiments was enriched for the conformer with pore-forming activity and had a 10-fold higher pore-forming specific activity than the bulk OprF population. Finally trypsin treatment, which preferentially cleaves the C-terminal domain of the two-domain conformer, did not affect the pore-forming activity of OprF nor did it digest the minority conformer whose residue 312 is exposed on cell surface. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Nikaido, H (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 426 Barker Hall, Berkeley, CA 94720 USA. EM nhiroshi@berkeley.edu FU NIAID NIH HHS [R01 AI009644-36, R37 AI009644, R01 AI009644-37, AI 09644, R01 AI009644] NR 55 TC 42 Z9 43 U1 0 U2 7 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 JUN 16 PY 2006 VL 281 IS 24 BP 16220 EP 16229 DI 10.1074/jbc.M600680200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700007 PM 16595653 ER PT J AU Nestorovich, EM Sugawara, E Nikaido, H Bezrukov, SM AF Nestorovich, EM Sugawara, E Nikaido, H Bezrukov, SM TI Pseudomonas aeruginosa porin OprF - Properties of the channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIPID-BILAYER-MEMBRANES; GRAM-NEGATIVE BACTERIA; OUTER-MEMBRANE; ESCHERICHIA-COLI; ALPHA-HEMOLYSIN; SINGLE-CHANNEL; PROTEIN OPRF; ION CHANNELS; PORES; POLYMERS AB Using ion channel reconstitution in planar lipid bilayers, we examined the channel-forming activity of subfractions of Pseudomonas aeruginosa OprF, which was shown to exist in two different conformations: a minority single domain conformer and a majority two-domain conformer ( Sugawara, E., Nestorovich, E. M., Bezrukov, S. M., and Nikaido, H. ( 2006) J. Biol. Chem. 281, 16220 16229). With the fraction depleted for the single domain conformer, we were unable to detect formation of any channels with well defined conductance levels. With the unfractionated OprF, we saw only rare channel formation. However, with the single domain-enriched fraction of OprF, we observed regular insertion of channels with highly reproducible conductances. Single OprF channels demonstrate rich kinetic behavior exhibiting spontaneous transitions between several subconformations that differ in ionic conductance and radius measured in polymer exclusion experiments. Although we showed that the effective radius of the most conductive conformation exceeds that of the general outer membrane porin of Escherichia coli, OmpF, we also found that a single OprF channel mainly exists in weakly conductive subconformations and switches to the fully open state for a short time only. Therefore, the low permeability of OprF reported earlier may be due to two factors: mainly to the paucity of the single domain conformer in the OprF population and secondly to the predominance of weakly conductive subconformations within the single domain conformer. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Bezrukov, SM (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 9 Rm,1N124,9 Mem Dr, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU NIAID NIH HHS [R01 AI009644-37, R01 AI009644, R01 AI009644-36] NR 30 TC 38 Z9 41 U1 0 U2 3 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 JUN 16 PY 2006 VL 281 IS 24 BP 16230 EP 16237 DI 10.1074/jbc.M600650200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700008 PM 16617058 ER PT J AU Gamero, AM Potla, R Wegrzyn, J Szelag, M Edling, AE Shimoda, K Link, DC Dulak, J Baker, DP Tanabe, Y Grayson, JM Larner, AC AF Gamero, AM Potla, R Wegrzyn, J Szelag, M Edling, AE Shimoda, K Link, DC Dulak, J Baker, DP Tanabe, Y Grayson, JM Larner, AC TI Activation of Tyk2 and Stat3 is required for the apoptotic actions of interferon-beta in primary pro-B cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; TYPE-1 INTERFERONS; GENE-EXPRESSION; I INTERFERON; ALPHA; GROWTH; INDUCTION; PHOSPHORYLATION; INHIBITION; DIFFERENTIATION AB The growth-inhibitory effects of type 1 interferons ( IFNs) ( IFN alpha/beta) are complex, and the role of apoptosis in their antigrowth effects is variable and not well understood. We have examined primary murine interleukin-7-dependent bone marrow-derived pro-B cells, where IFN beta, but not IFN alpha, induces programmed cell death ( PCD). IFN beta-stimulated apoptosis is the same in pro-B cells derived from wild type and Stat1(-/-) mice. However, in pro-B cells from Tyk2(-/-) mice, where there is normal activation of Stat1 and Stat2, IFN beta-stimulated PCD is not observed. Loss of B cells in lymphocytic choriomeningitis virus-infected mice has been shown to be mediated through the expression of IFN alpha/beta( 1). In wild type mice infected with lymphocytic choriomeningitis virus, there is a greater loss of B cells in the bone marrow and spleen than in Tyk2(-/-) mice infected with the virus, suggesting that the expression of this kinase plays an in vivo role in IFN alpha/beta-mediated PCD. In contrast to IFN beta-stimulated tyrosine phosphorylation of Stat1 and Stat2, Stat3 tyrosine phosphorylation is defective in Tyk2(-/-) pro-B cells, suggesting that this Stat family member is required for apoptosis. In support of this hypothesis, inhibition of Stat3 activation in wild type B cells reverses the apoptotic effects of IFN beta. Furthermore, expression of a constitutively active form of Stat3 in Tyk2(-/-) B cells partially restores IFN beta-stimulated PCD. These results demonstrate an important role of Tyk2-mediated tyrosine phosphorylation of Stat3 in the ability of IFN beta to stimulate apoptosis of primary pro-B cells. C1 Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, Cleveland, OH 44195 USA. NCI, Expt Immunol Lab, NIH, Frederick, MD 21702 USA. Kyushu Univ, Fukuoka 8128582, Japan. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. Jagiellonian Univ, Dept Med Biotechnol, PL-30387 Krakow, Poland. Cleveland State Univ, Dept Biol, Cleveland, OH 44195 USA. Biogen Idec Inc, Cambridge, MA 02142 USA. Wake Forest Univ, Sch Med, Dept Microbiol & Immunol, Winston Salem, NC 27157 USA. Niigata Univ, Sch Med, Dept Med, Niigata 9518510, Japan. RP Larner, AC (reprint author), Cleveland Clin Fdn, Dept Immunol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM larnera@ccf.org NR 32 TC 22 Z9 24 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 JUN 16 PY 2006 VL 281 IS 24 BP 16238 EP 16244 DI 10.1074/jbc.M509516200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700009 PM 16601124 ER PT J AU Chen, BS Braud, S Badger, JD Isaac, JTR Roche, KW AF Chen, BS Braud, S Badger, JD Isaac, JTR Roche, KW TI Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; AMPA RECEPTOR; SYNAPTIC PLASTICITY; DEVELOPING CEREBELLUM; GLUTAMATE RECEPTORS; SURFACE EXPRESSION; GUANYLATE KINASES; GLUR1 SUBUNIT; C-TERMINUS; TRAFFICKING AB NR2C-containing N-methyl-D-aspartate (NMDA) receptors are highly expressed in cerebellar granule cells where they mediate the majority of current in the adult. NMDA receptors composed of NR1/NR2C exhibit a low conductance and reduced sensitivity to Mg2+, compared with the more commonly studied NR2A- and NR2B-containing receptors. Despite these interesting features, very little is known about the regulation of NR2C function. Here we investigate the role of phosphorylation of NR2C in regulating NMDA receptor trafficking and ion channel properties. We identify a phosphorylation site, serine 1244 (Ser(1244)), near the extreme COOH terminus of NR2C, which is phosphorylated by both cAMP-dependent protein kinase and protein kinase C. This residue is located adjacent to the consensus PDZ ligand, a region that regulates protein-protein interactions and receptor trafficking in NR2A and NR2B. We show that Ser(1244) on NR2C is phosphorylated in vitro, in heterologous cells, and in neurons. Moreover, we demonstrate for the first time that NR2C interacts with the PSD-95 family of PDZ domain-containing proteins but that phosphorylation of Ser(1244) does not influence this PDZ interaction. Furthermore, Ser(1244) phosphorylation does not regulate surface expression of NR1/NR2C receptors. However, we find that this site does regulate the kinetics of the ion channel: a phosphomimetic mutation at Ser(1244) accelerates both the rise and decay of NMDA-evoked currents in excised patches from HEK-293 cells. Therefore, phosphorylation of Ser(1244) does not regulate trafficking but unexpectedly affects ion channel function, suggesting that phosphorylation of Ser(1244) on NR2C may be important in defining the functional properties of NMDA receptor-mediated currents in the cerebellum. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Bristol, Dept Anat, MRC, Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. RP Roche, KW (reprint author), NINDS, NIH, Bldg 35,Rm 2C903, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov RI Chen, Bo-Shiun/E-2736-2010; Chen, Bo-Shiun/H-4633-2012; OI Roche, Katherine/0000-0001-7282-6539 FU Intramural NIH HHS; Wellcome Trust NR 35 TC 41 Z9 41 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 JUN 16 PY 2006 VL 281 IS 24 BP 16583 EP 16590 DI 10.1074/jbc.M513029200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700050 PM 16606616 ER PT J AU Yamamoto, Y Moore, R Hess, HA Guo, GL Gonzalez, FJ Korach, KS Maronpot, RR Negishi, M AF Yamamoto, Y Moore, R Hess, HA Guo, GL Gonzalez, FJ Korach, KS Maronpot, RR Negishi, M TI Estrogen receptor alpha mediates 17 alpha-ethynylestradiol causing hepatotoxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; SALT EXPORT PUMP; PRIMARY BILIARY-CIRRHOSIS; HEPATIC GENE-EXPRESSION; BILE-ACID SYNTHESIS; NUCLEAR RECEPTORS; INTRAHEPATIC CHOLESTASIS; LIPID HOMEOSTASIS; LIVER TOXICITY AB Estrogens are known to cause hepatotoxicity such as intrahepatic cholestasis in susceptible women during pregnancy, after administration of oral contraceptives, or during postmenopausal replacement therapy. Enterohepatic nuclear receptors including farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive active/androstane receptor (CAR) are important in maintaining bile acid homeostasis and protecting the liver from bile acid toxicity. However, no nuclear receptor has been implicated in the mechanism for estrogen-induced hepatotoxicity. Here Era(-/-), Erb(-/-), Fxr(-/-), Pxr(-/-), and Car(-/-) mice were employed to show that Era(-/-) mice were resistant to synthetic estrogen 17 alpha-ethynylestradiol (EE2)-induced hepatotoxicity as indicated by the fact that the EE2-treated Era(-/-) mice developed none of the hepatotoxic phenotypes such as hepatomegaly, elevation in serum bile acids, increase of alkaline phosphatase activity, liver degeneration, and inflammation. Upon EE2 treatment, estrogen receptor alpha(ER alpha) repressed the expression of bile acid and cholesterol transporters ( bile salt export pump (BSEP), Na+/taurocholate cotransporting polypeptide (NTCP), OATP1, OATP2, ABCG5, and ABCG8) in the liver. Consistently, biliary secretions of both bile acids and cholesterol were markedly decreased in EE2-treated wild-type mice but not in the EE2-treated Era(-/-) mice. In addition, ER alpha up-regulated the expression of CYP7B1 and down-regulated the CYP7A1 and CYP8B1, shifting bile acid synthesis toward the acidic pathway to increase the serum level of beta-muricholic acid. ER beta, FXR, PXR, and CAR were not involved in regulating the expression of bile acid transporter and biosynthesis enzyme genes following EE2 exposure. Taken together, these results suggest that ER alpha- mediated repression of hepatic transporters and alterations of bile acid biosynthesis may contribute to development of the EE2-induced hepatotoxicity. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS NR 43 TC 87 Z9 92 U1 2 U2 12 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 JUN 16 PY 2006 VL 281 IS 24 BP 16625 EP 16631 DI 10.1074/jbc.M602723200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700055 PM 16606610 ER PT J AU Dixit, VD Weeraratna, AT Yang, HW Bertak, D Cooper-Jenkins, A Riggins, GJ Eberhart, CG Taub, DD AF Dixit, VD Weeraratna, AT Yang, HW Bertak, D Cooper-Jenkins, A Riggins, GJ Eberhart, CG Taub, DD TI Ghrelin and the growth hormone secretagogue receptor constitute a novel autocrine pathway in astrocytoma motility SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DES-ACYL GHRELIN; PROTEIN-KINASE-C; HUMAN PITUITARY-ADENOMAS; CELL-LINES; BIOLOGICAL-ACTIVITY; ENDOTHELIAL-CELLS; MESSENGER-RNA; BRAIN-TUMORS; KAPPA-B; EXPRESSION AB Originally thought of as a stomach-derived endocrine peptide acting via its receptors in the central nervous system to stimulate food intake and growth hormone expression, ghrelin and its receptor ( growth hormone secretagogue receptor (GHS-R)) are widely expressed in a number of organ systems, including cancer cells. However, the direct functional role of ghrelin and its receptor in tumors of central nervous system origin remains to be defined. Here, we demonstrate that the human astrocytoma cell lines U-118, U-87, CCF-STTG1, and SW1088 express 6-, 11-, 15-, and 29-fold higher levels of GHS-R compared with primary normal human astrocytes. The ligation of GHS-R by ghrelin on these cells resulted in an increase in intracellular calcium mobilization, protein kinase C activation, actin polymerization, matrix metalloproteinase-2 activity, and astrocytoma motility. In addition, ghrelin led to actin polymerization and membrane ruffling on cells, with the specific co-localization of the small GTPase Rac1 with GHS-R on the leading edge of the astrocytoma cells and imparting the tumor cells with a motile phenotype. Disruption of the endogenous ghrelin/GHS-R pathway by RNA interference resulted in diminished motility, matrix metalloproteinase activity, and Rac expression, whereas tumor cells stably overexpressing GHS-R exhibited increased cell motility. The relevance of ghrelin and GHS-R expression was verified in clinically relevant tissues from 20 patients with oligodendrogliomas and grade II-IV astrocytomas. Analysis of a central nervous system tumor tissue microarray revealed that strong GHS-R and ghrelin expression was significantly more common in high grade tumors compared with low grade ones. Together, these findings suggest a novel role for the ghrelin/ GHS-R axis in astrocytoma cell migration and invasiveness of cancers of central nervous system origin. C1 NIA, Clin Immunol Sect, Immunol Lab, NIH,Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Clin Immunol Sect, Immunol Lab, NIH,Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Taubd@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000758-10] NR 67 TC 41 Z9 44 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 JUN 16 PY 2006 VL 281 IS 24 BP 16681 EP 16690 DI 10.1074/jbc.M600223200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051MR UT WOS:000238165700062 PM 16527811 ER PT J AU Pirnay, S Herve, F Bouchonnet, S Perrin, B Baud, FJ Ricordel, I AF Pirnay, S Herve, F Bouchonnet, S Perrin, B Baud, FJ Ricordel, I TI Liquid chromatographic-electrospray ionization mass spectrometric quantitative analysis of buprenorphine, norbuprenorphine, nordiazepam and oxazepam in rat plasma SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE buprenorphine; norbuprenorphine; nordiazepam; oxazepam; LC-ESI-MS; rat plasma; validation ID SENSITIVE METHOD; WHOLE-BLOOD; BENZODIAZEPINES; FLUNITRAZEPAM; METABOLITES; METHADONE; HUMANS; HEROIN; BLOCKADE; DIAZEPAM AB A liquid chromatographic-mass spectrometric method with electrospray ionization is presented for the simultaneous determination of buprenorphine, nordiazepam and their pharmacologically active metabolites, norbuprenorphine and oxazepam, in rat plasma. The drugs were extracted from plasma by liquid-liquid extraction and chromatographically separated using a gradient elution of aqueous ammonium formate and acetonitrile. Following electrospray ionization, the analytes were quantified in the single ion storage mode. The assay was validated according to current acceptance criteria for bioanalytical method validation. It was proved to be linear from 0.7 to 200 ng/ml plasma for buprenorphine, 1.0 to 200 ng/ml for norbuprenorphine, 2.0 to 200 ng/ml for nordiazepam, and from 5.0 to 200 ng/ml for oxazepam. The average recoveries of buprenorphine, norbuprenorphine, nordiazepam and oxazepam were 89, 39, 88 and 82%, respectively, with average coefficients of variation ranging from 1.8 to 14.3%. The limits of quantitation for these drugs were 0.7, 1.0, 2.0 and 5.0 ng/ml, respectively, with associated precisions within 17% and accuracies within +/- 18% of the nominal values. Both the intra- and inter-assay precision values did not exceed 11.3% for the four analytes. Intra- and inter-assay accuracies lay within +/- 15% of the nominal values. The validated method was applied to the determination of buprenorphine, norbuprenorphine, nordiazepam, and oxazepam in plasma samples collected from rats at various times after intravenous administration of buprenorphine and nordiazepam. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA. Lab Toxicol Prefecture Police, F-75012 Paris, France. Univ Paris 07, INSERM, U705, CNRS,UMR 7157, F-75475 Paris, France. Univ Paris 05, Hop Fernand Widal, F-75475 Paris 10, France. Ecole Polytech, Dept Chim Mecanismes Reactionnels, F-91128 Palaiseau, France. RP Pirnay, S (reprint author), NIDA, Chem & Drug Metab Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM pirnaystephane@yahoo.com NR 41 TC 13 Z9 16 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUN 16 PY 2006 VL 41 IS 4 BP 1135 EP 1145 DI 10.1016/j.jpba.2006.02.020 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 055ZV UT WOS:000238491100008 PM 16554136 ER PT J AU Kalueff, AV Avgustinovich, DF Kudryavtseva, NN Murphy, DL AF Kalueff, AV Avgustinovich, DF Kudryavtseva, NN Murphy, DL TI BDNF in anxiety and depression SO SCIENCE LA English DT Letter ID ELEVATED PLUS-MAZE; NEUROTROPHIC FACTOR; MOOD DISORDERS C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10, Bethesda, MD 20892 USA. NR 13 TC 21 Z9 23 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 16 PY 2006 VL 312 IS 5780 BP 1598 EP 1598 DI 10.1126/science.312.5780.1598 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053EO UT WOS:000238288600016 PM 16778038 ER PT J AU Matoba, S Kang, JG Patino, WD Wragg, A Boehm, M Gavrilova, O Hurley, PJ Bunz, F Hwang, PM AF Matoba, S Kang, JG Patino, WD Wragg, A Boehm, M Gavrilova, O Hurley, PJ Bunz, F Hwang, PM TI p53 regulates mitochondrial respiration SO SCIENCE LA English DT Article ID CANCER-CELLS; LIFE-SPAN; DNA-DAMAGE; MICE; METABOLISM; GENES; IMPAIRMENT; DEFICIENCY; PATHWAYS; CAPACITY AB The energy that sustains cancer cells is derived preferentially from glycolysis. This metabolic change, the Warburg effect, was one of the first alterations in cancer cells recognized as conferring a survival advantage. Here, we show that p53, one of the most frequently mutated genes in cancers, modulates the balance between the utilization of respiratory and glycolytic pathways. We identify Synthesis of Cytochrome c Oxidase 2 ( SCO2) as the downstream mediator of this effect in mice and human cancer cell lines. SCO2 is critical for regulating the cytochrome c oxidase ( COX) complex, the major site of oxygen utilization in the eukaryotic cell. Disruption of the SCO2 gene in human cancer cells with wild-type p53 recapitulated the metabolic switch toward glycolysis that is exhibited by p53-deficient cells. That SCO2 couples p53 to mitochondrial respiration provides a possible explanation for the Warburg effect and offers new clues as to how p53 might affect aging and metabolism. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21231 USA. RP Hwang, PM (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Intramural NIH HHS NR 32 TC 871 Z9 911 U1 10 U2 75 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 16 PY 2006 VL 312 IS 5780 BP 1650 EP 1653 DI 10.1126/science.1126863 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053EO UT WOS:000238288600045 PM 16728594 ER PT J AU Pisitkun, P Deane, JA Difilippantonio, MJ Tarasenko, T Satterthwaite, AB Bolland, S AF Pisitkun, P Deane, JA Difilippantonio, MJ Tarasenko, T Satterthwaite, AB Bolland, S TI Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplication SO SCIENCE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TOLL-LIKE RECEPTORS; DEFICIENT MICE; YAA MUTATION; Y-CHROMOSOME; DISEASE; ENGAGEMENT; BTK AB Antibodies against nuclear self-antigens are characteristic of systemic autoimmunity, although mechanisms promoting their generation and selection are unclear. Here, we report that B cells containing the Y-linked autoimmune accelerator (Yaa) locus are intrinsically biased toward nucleolar antigens because of increased expression of TLR7, a single-stranded RNA-binding innate immune receptor. The TLR7 gene is duplicated in Yaa mice because of a 4-Megabase expansion of the pseudoautosomal region. These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NCI, Sect Canc Genom, Henet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Texas SW, Dept Internal Med, Dallas, TX 75390 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM sbolland@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 433 Z9 450 U1 2 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 16 PY 2006 VL 312 IS 5780 BP 1669 EP 1672 DI 10.1126/science.1124978 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053EO UT WOS:000238288600051 PM 16709748 ER PT J AU Qi, H Egen, JG Huang, AYC Germain, RN AF Qi, Hai Egen, Jackson G. Huang, Alex Y. C. Germain, Ronald N. TI Extrafollicular activation of lymph node B cells by antigen-bearing dendritic cells SO SCIENCE LA English DT Article ID ANTIBODY-RESPONSES; IN-VIVO; LYMPHOCYTES; FOLLICLES; TRANSPORT; MEMBRANE; INTERACT; MOTILITY; PROTEIN; CORTEX AB In contrast to naive T cells that recognize short antigen-derived peptides displayed by specialized antigen-presenting cells, immunoglobulin receptors of B lymphocytes primarily recognize intact proteins. How and where within a lymph node such unprocessed antigens become available for naive B cell recognition is not clear. We used two-photon intravital imaging to show that, after exiting high-endothelial venules and before entry into lymph node follicles, B cells survey locally concentrated dendritic cells. Engagement of the B cell receptor by the dendritic cell (DC)-associated antigen leads to lymphocyte calcium signaling, migration arrest, antigen acquisition, and extrafollicular accumulation. These findings suggest a possible role for antigen-specific B-DC interactions in promoting T cell - dependent antibody responses in vivo. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov RI Qi, Hai/A-3955-2009; OI Egen, Jackson/0000-0003-2053-0837; Huang, Alex/0000-0002-5701-4521 FU Intramural NIH HHS NR 29 TC 302 Z9 311 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 16 PY 2006 VL 312 IS 5780 BP 1672 EP 1676 DI 10.1126/science.1125703 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053EO UT WOS:000238288600052 PM 16778060 ER PT J AU Pope, SK Kritchevsky, SB Ambrosone, C Yaffe, K Tylavsky, F Simonsick, EM Rosano, C Stewart, S Harris, T AF Pope, SK Kritchevsky, SB Ambrosone, C Yaffe, K Tylavsky, F Simonsick, EM Rosano, C Stewart, S Harris, T CA Hlth ABC Study TI Myeloperoxidase polymorphism and cognitive decline in older adults in the health, aging, and body composition study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cognition; ethnic groups; peroxidase; polymorphism; genetic; prospective studies ID ALZHEIMERS-DISEASE; RISK; GENE; ASSOCIATION; MPO; AGE AB Myeloperoxidase, an antimicrobial enzyme, produces oxidative free radicals. Rarely found in normal brain tissue, myeloperoxidase has been detected in microglia associated with Alzheimer's disease plaques. The authors examined a G-463A polymorphism in the promoter region of the myeloperoxidase gene (MPO) to determine the relation of MPO variants to cognitive decline over 4 years in a cohort of adults, aged 70-79 years at baseline (1997-1998), recruited from Memphis, Tennessee, and Pittsburgh, Pennsylvania, into the Health, Aging, and Body Composition Study. In this sample, 8% of the participants had the AA, 36.9% the AG, and 55.2% the GG genotype of MPO. The frequency of AA and AG genotypes was higher in Blacks than Whites (11.2% vs. 5.9%, and 44.1% vs. 32.9%, respectively). Multivariate logistic regression analyses showed that, for participants with the MPO AA genotype, cognitive decline was 1.58 (95% confidence interval: 1.07, 2.35) times more likely than for participants with the AG genotype and 1.96 (95% confidence interval: 1.33, 2.88) times more likely than for those with the GG genotype. Interactions between MPO and race, sex, or the apolipoprotein gene were not significant. In this sample, MPO AA, associated with decreased production of myeloperoxidase, was found to be a risk factor for cognitive decline. C1 Univ Arkansas Med Sci, Dept Geriatr, Coll Med, Little Rock, AR 72205 USA. Wake Forest Univ, Sch Med, J Paul Sticht Ctr Aging, Winston Salem, NC USA. Roswell Pk Canc Inst, Div Canc Prevent & Populat Sci, Buffalo, NY USA. Univ Calif San Francisco, Dept Psychiat Neurol & Epidemiol, San Francisco, CA USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. NIA, Intramural Res Program, Bethesda, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Arkansas Med Sci, Coll Med, Dept Biostat, Little Rock, AR USA. NIA, Clin Res Branch, Baltimore, MD USA. RP Pope, SK (reprint author), Univ Arkansas Med Sci, Dept Geriatr, Coll Med, 4301 W Markham St Slot 808, Little Rock, AR 72205 USA. EM skpope@uams.edu OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Kritchevsky, Stephen/0000-0003-3336-6781 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2106, N01-AG-2103, N01-AG-6-2101, K01-AG-20173] NR 25 TC 16 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2006 VL 163 IS 12 BP 1084 EP 1090 DI 10.1093/aje/kwj146 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 055BL UT WOS:000238424900004 PM 16641309 ER PT J AU LeVan, TD Koh, WP Lee, HP Koh, D Yu, MC London, SJ AF LeVan, Tricia D. Koh, Woon-Puay Lee, Hin-Peng Koh, David Yu, Mimi C. London, Stephanie J. TI Vapor, dust, and smoke exposure in relation to adult-onset asthma and chronic respiratory symptoms - The Singapore Chinese Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE asthma; bronchitis; chronic; occupational diseases; occupational exposure; pulmonary disease; chronic obstructive ID OBSTRUCTIVE PULMONARY-DISEASE; AIRWAYS DYSFUNCTION SYNDROME; OCCUPATIONAL EXPOSURES; GENERAL-POPULATION; VENTILATORY FUNCTION; AIR-POLLUTION; LUNG-FUNCTION; COMMUNITY; WORKERS; BURDEN AB Occupational factors contribute to a significant fraction of respiratory disease and symptoms. The authors evaluated the role of occupational exposures in asthma, chronic bronchitis, and respiratory symptoms in the Singapore Chinese Health Study, a population-based cohort of adults aged 45-74 years at enrollment in 1993-1998. Information on occupations and occupational exposures was collected at enrollment for 52,325 subjects for whom respiratory outcomes were obtained via follow-up interviews in 1999-2004. Exposure to dusts from cotton, wood, metal, minerals, and/or asbestos was associated with nonchronic cough and/or phlegm (odds ratio (OR) = 1.19, 95% confidence interval (Cl): 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% Cl: 1.01, 1.57), and adult-onset asthma (OR = 1.14, 95% Cl: 1.00, 1.30). Cotton dust was the major contributor to respiratory symptoms. Vapor exposure from chemical solvents, dyes, cooling oils, paints, wood preservatives, and/or pesticides was associated with nonchronic cough or phlegm (OR = 1.14, 95% Cl: 1.03, 1.27), chronic dry cough (OR = 1.55, 95% Cl: 1.19, 2.01), and adult-onset asthma (OR = 1.34, 95% Cl: 1.15, 1.56). Chemical solvents, cooling oils, and pesticides were the major contributors to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. C1 Univ Arizona, Arizona Resp Ctr, Tucson, AZ USA. Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Community Occupat & Family Med, Singapore 117548, Singapore. Univ Minnesota, Canc Ctr, Minneapolis, MN USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. RP London, SJ (reprint author), Natl Inst Environm Hlth Sci, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [R01 CA080205, R01 CA080205-05, R01 CA80205]; NIEHS NIH HHS [Z01 ES043012, K01 ES000386, K01 ES000386-05, K01 ES00386, Z01 ES043012-07] NR 53 TC 38 Z9 38 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2006 VL 163 IS 12 BP 1118 EP 1128 DI 10.1093/aje/kwj144 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 055BL UT WOS:000238424900008 PM 16707657 ER PT J AU Hoppin, JA Umbach, DM London, SJ Lynch, CF Alavanja, MCR Sandler, DP AF Hoppin, JA Umbach, DM London, SJ Lynch, CF Alavanja, MCR Sandler, DP TI Pesticides associated with wheeze among commercial pesticide applicators in the Agricultural Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; insecticides; occupational exposure; organophosphates; pesticides; signs and symptoms; respiratory; sulfonylurea compounds ID RESPIRATORY SYMPTOMS; AIRWAY HYPERREACTIVITY; ASTHMA; FARMERS; QUESTIONNAIRE; INHIBITION; PREDICTORS; MECHANISMS; SMOKING; IOWA AB Pesticides are potential risk factors for respiratory disease among farmers, but farmers are also exposed to other respiratory toxicants. To explore the association of pesticides with wheeze in a population without other farming exposures, the authors analyzed data from 2,255 Iowa commercial pesticide applicators enrolled in the Agricultural Health Study. Controlling for age, smoking status, asthma and atopy history, and body mass index, the authors calculated odds ratios for the relationship between wheeze and 36 individual pesticides participants had used during the year before enrollment (1993-1997). Eight of 16 herbicides were associated with wheeze in single-agent models; however, the risk was almost exclusively associated with the herbicide chlorimuron-ethyl (odds ratio (OR) = 1.62, 95% confidence interval (Cl): 1.25, 2.10). Inclusion of chlorimuron-ethyl in models for the other herbicides virtually eliminated the associations. The odds ratios for four organophosphate insecticides (terbufos, fonofos, chlorpyrifos, and phorate) were elevated when these chemicals were modeled individually and remained elevated, though attenuated somewhat, when chlorimuron-ethyl was included. The association for dichlorvos, another organophosphate insecticide, was not attenuated by chlorimuron-ethyl (OR = 2.48, 95% Cl: 1.08, 5.66). Dose-response trends were observed for chlorimuron-ethyl, chlorpyrifos, and phorate; the strongest odds ratio was for applying chlorpyrifos on more than 40 days per year (OR = 2.40, 95% Cl: 1.24, 4.65). These results add to the emerging literature linking organophosphate insecticides and respiratory health and suggest a role for chlorimuron-ethyl. C1 US Dept Hlth & Human Serv, Nalt Inst Environm Hlth Sci, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. US Dept Hlth & Human Serv, Nalt Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. US Dept Hlth & Human Serv, NCI, Occupat Epidemiol Branch, NIH, Rockville, MD USA. RP Hoppin, JA (reprint author), US Dept Hlth & Human Serv, Nalt Inst Environm Hlth Sci, Epidemiol Branch, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 19 TC 39 Z9 40 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2006 VL 163 IS 12 BP 1129 EP 1137 DI 10.1093/aje/kwj138 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 055BL UT WOS:000238424900009 PM 16611668 ER PT J AU Martinez, FJ Foster, G Curtis, JL Criner, G Weinmann, G Fishman, A DeCamp, MM Benditt, J Sciurba, F Make, B Mohsenifar, Z Diaz, P Hoffman, E Wise, R AF Martinez, FJ Foster, G Curtis, JL Criner, G Weinmann, G Fishman, A DeCamp, MM Benditt, J Sciurba, F Make, B Mohsenifar, Z Diaz, P Hoffman, E Wise, R CA NETT Res Grp TI Predictors of mortality in patients with emphysema and severe airflow obstruction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; computed tomography; mortality; prognosis; pulmonary function ID PULMONARY-DISEASE; OXYGEN-THERAPY; NUTRITIONAL-STATUS; EXERCISE CAPACITY; WALK DISTANCE; HEALTH-STATUS; SURVIVAL; PROGNOSIS; COPD; QUESTIONNAIRE AB Purpose: Limited data exist describing risk factors for mortality in patients having predominantly emphysema. Subjects and Methods: A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Results: Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p = 0.001), oxygen utilization (p = 0.04), lower total lung capacity % predicted (p = 0.05), higher residual volume predicted (p = 0.04), lower maximal cardiopulmonary exercise testing workload (p = 0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p = 0.005), and lower upper-to-lower-lung perfusion ratio (p = 0.007), and modified BODE (p = 0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p = 0.005), but not in multivariate analysis (p = 0.21). Conclusion: Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death. C1 Univ Michigan Hlth Syst, Div Pulm & Crit Care Med, Ann Arbor, MI USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NHLBI, Div Lung Dis, Bethesda, MD 20892 USA. Temple Univ, Div Pulm & Crit Care Med, Dept Med, Philadelphia, PA 19122 USA. Univ Pittsburgh, Div Pulm & Crit Care Med, Pittsburgh, PA USA. Univ Penn, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA. Beth Israel Deaconess Med Ctr, Thorac Surg Sect, Boston, MA 02215 USA. Univ Washington, Dept Med, Seattle, WA USA. Natl Jewish Med & Res Ctr, Div Pulm Sci, Denver, CO USA. Cedars Sinai Med Ctr, Div Pulm Med, Los Angeles, CA 90048 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. RP Martinez, FJ (reprint author), 1500 E Med Ctr Dr,3916 Taubman Ctr, Ann Arbor, MI 48109 USA. EM fmartine@umich.edu OI Curtis, Jeffrey/0000-0001-5191-4847; Wise, Robert/0000-0002-8353-2349 FU NHLBI NIH HHS [N01HR76105, N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, N01HR76119] NR 42 TC 212 Z9 215 U1 2 U2 17 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2006 VL 173 IS 12 BP 1326 EP 1334 DI 10.1164/rccm.200510-1677OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 052CI UT WOS:000238208100006 PM 16543549 ER PT J AU Pastrana, DV FitzGerald, DJ AF Pastrana, DV FitzGerald, DJ TI A nonradioactive, cell-free method for measuring protein synthesis inhibition by Pseudomonas exotoxin SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE toxin; nonradioactive; inhibition of protein synthesis; pseudomonas; ADP-ribosylation; reticulocyte ID ELONGATION FACTOR-II; SEGREGATION GENE CSE1; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; ADP-RIBOSYLATION; MEDIATED APOPTOSIS; HUMAN HOMOLOG; DOMAIN-II; AERUGINOSA; RIBOSYLTRANSFERASE AB Pseudomonas exotoxin A (PE) inhibits protein synthesis by NAD-dependent ADP-ribosylation of eukaryotic elongation factor 2. Traditionally, toxin activity has been characterized, either in living cells or cell-free systems, using radioactive, compounds for quantification. The increased costs of radioactive waste disposal together with heightened security concerns have made the use of radioactive isotopes less attractive for routine laboratory assays. We therefore adapted a cell-free rabbit reticulocyte in vitro transcription-translation system that utilizes a reporter (beta-galactosidase) to measure toxin activity. The assay for PE is rapid, scalable, log-linear, NAD dependent and can be used to assess the neutralizing activity of anti-PE antibody preparations. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, Mol Biol Lab, CCR, Biotherapy Sect, Bethesda, MD 20892 USA. RP FitzGerald, DJ (reprint author), NCI, Mol Biol Lab, CCR, Biotherapy Sect, 37-5124,37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM djpf@helix.nih.gov FU Intramural NIH HHS NR 31 TC 4 Z9 4 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 15 PY 2006 VL 353 IS 2 BP 266 EP 271 DI 10.1016/j.ab.2006.03.043 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 052BE UT WOS:000238204700014 PM 16647035 ER PT J AU Navratilova, I Pancera, M Wyatt, RT Myszka, DG AF Navratilova, I Pancera, M Wyatt, RT Myszka, DG TI A biosensor-based approach toward purification and crystallization of G protein-coupled receptors SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE surface plasmon resonance; SPR; protein-protein; kinetics ID BINDING; CCR5; EXPRESSION; RHODOPSIN; ENTRY AB Biacore technology was used to develop an affinity purification method and screen cocrystallization conditions for the chemokine receptor CCR5. We characterized the binding of nine HIV gp120 variants and identified a truncated construct (YU2DV1V2) that bound CCR5 independent of CD4. This construct was used in an affinity purification step to improve the activity of detergent-solubilized receptor by approximately 300%. The biosensor was also used to screen receptor binding activity automatically under 50 different crystallization conditions. We found that high-molecular-weight polyethylene glycols (PEGs 4000 and 8000 Da) most often stabilized the receptor and improved complex formation with potential cocrystallization partners such as conformationally sensitive monoclonal antibodies and gp120. Our results show how biosensors can provide unique insights into receptor purification methods and reveal the effects of crystallization conditions on complex formation. Importantly, these methods can be readily applied to other systems. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Myszka, DG (reprint author), Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. EM dmyszka@cores.utah.edu FU NIGMS NIH HHS [P01 GM66521] NR 8 TC 21 Z9 22 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUN 15 PY 2006 VL 353 IS 2 BP 278 EP 283 DI 10.1016/j.ab.2006.03.049 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 052BE UT WOS:000238204700016 PM 16647033 ER PT J AU Roebuck-Spencer, TM Yarboro, C Nowak, M Takada, K Jacobs, G Lapteva, L Weickert, T Volpe, B Diamond, B Illei, G Bleiberg, J AF Roebuck-Spencer, TM Yarboro, C Nowak, M Takada, K Jacobs, G Lapteva, L Weickert, T Volpe, B Diamond, B Illei, G Bleiberg, J TI Use of computerized assessment to predict neuropsychological functioning and emotional distress in patients with systemic lupus erythematosus SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE lupus; cognitive functioning; neuropsychological testing; ANAM ID OVERT NEUROPSYCHIATRIC MANIFESTATIONS; MILD BRAIN INJURY; COGNITIVE IMPAIRMENT; PSYCHIATRIC-DISORDER; PREVALENCE; DYSFUNCTION; FATIGUE; MOOD; PERFORMANCE; DEFICITS AB Objective. Cognitive dysfunction and neuropsychiatric disturbance are common in systemic lupus erythematosus (SLE). This study addressed the ability of the Automated Neuropsychological Assessment Metrics (ANAM), a computerized cognitive testing battery consisting of cognitive subtests, a sleepiness rating scale, and a mood scale, to predict neuropsychological status in patients with SLE. Methods. Sixty individuals with SLE and no overt neuropsychiatric symptoms were administered ANAM to determine its validity as a screening measure of cognitive dysfunction and emotional distress in SLE. Results. Performance on ANAM was compared with results of a consecutively administered, 2-hour battery of traditional neuropsychological tests and the Beck Depression Inventory II (BDI-II). Individual ANAM cognitive test scores were significantly correlated with most neuropsychological tests, particularly those measuring psychomotor processing speed and executive functioning. Using logistic regression, ANAM cognitive subtests successfully predicted individuals with SLE who had probable versus no impairment after controlling for premorbid levels of cognitive ability. Sensitivity of group classification was 76.2% and specificity was 82.8%, with 80% correct classification overall. ANAM's ability to predict neuropsychological functioning remained even after controlling for subjective reports of depressed mood and current sleepiness. Further, the ANAM mood scale was significantly correlated with the BDI-II (r = 0.67, P < 0.001), indicating its potential future use as a screening tool for emotional distress. Conclusion. ANAM shows promise as a time- and cost-efficient tool for screening and monitoring cognitive and emotional functioning in SLE, and can indicate when a more thorough neuropsychological investigation is warranted. C1 Natl Rehabil Hosp, Ctr Cognit Neurosci, Washington, DC 20010 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Columbia Univ, Coll Med, New York, NY USA. RP Roebuck-Spencer, TM (reprint author), Natl Rehabil Hosp, Ctr Cognit Neurosci, 102 Irving St NW, Washington, DC 20010 USA. EM Tresa.roebuck@medstar.net OI Volpe, Bruce/0000-0002-1098-1848; Bleiberg, Joseph/0000-0003-0867-5494 NR 53 TC 32 Z9 32 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2006 VL 55 IS 3 BP 434 EP 441 DI 10.1002/art.21992 PG 8 WC Rheumatology SC Rheumatology GA 051PL UT WOS:000238172900014 PM 16739211 ER PT J AU Einat, H Manji, HK AF Einat, H Manji, HK TI Cellular plasticity cascades: Genes-to-behavior pathways in animal models of bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Review DE mania; underlying mechanisms; cellular plasticity ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3; FORCED SWIM TEST; NIGROSTRIATAL DOPAMINERGIC FUNCTION; CONDITIONED PLACE PREFERENCE; LITHIUM-PILOCARPINE SEIZURES; MANIC-DEPRESSIVE ILLNESS; GLUCOCORTICOID-RECEPTOR; NEUROTROPHIC FACTOR; IN-VIVO AB Background: Despite extensive research, the molecular/cellular underpinnings of bipolar disorder (BD) remain to be fully elucidated. Recent data has demonstrated that mood stabilizers exert major effects on signaling that regulate cellular plasticity; however, a direct extrapolation to mechanisms of disease demands proof that manipulation of candidate genes, proteins, or pathways result in relevant behavioral changes. Methods. We critique and evaluate the behavioral changes induced by manipulation of cellular plasticity cascades implicated in BD. Results: Not surprisingly, the behavioral data suggest that several important signaling molecules might play important roles in mediating facets of the complex symptomatology of BD. Notably, the protein kinase C and extracellular signal-regulated kinase cascades might play important roles in the antimanic effects of mood stabilizers, whereas glycogen syntbase kinase (GSK)-3 might mediate facets of lithium's antimanic/antidepressant actions. Glucocorticoid receptor (GR) modulation also seems to be capable to inducing affective-like changes observed in mood disorders. And Bcl-2, amino-3- ydroxy-5-methylisoxazole-4-propionic acid receptors, and inositol homeostasis represent important pharmacological targets for mood stabilizers, but additional behavioral research is needed to more fully delineate their behavioral effects. Conclusions: Behavioral data support the notion that regulation of cellularplasticity is involved in affective-like behavioral changes observed in BD. These findings are leading to the development of novel therapeutics for this devastating illness. C1 Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. NIMH, Mood & Anziety Disorders Program, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Einat, H (reprint author), Univ Minnesota, Coll Pharm, 376 Kirby Plaza,1208 Kirby Dr, Duluth, MN 55812 USA. EM heinat@d.umn.edu RI Einat, Haim/A-7203-2009 FU Intramural NIH HHS NR 146 TC 87 Z9 88 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2006 VL 59 IS 12 BP 1160 EP 1171 DI 10.1016/j.biopsych.2005.11.004 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 058VI UT WOS:000238692300008 PM 16457783 ER PT J AU Chen, JS Lipska, BK Weinberger, DR AF Chen, JS Lipska, BK Weinberger, DR TI Genetic mouse models of schizophrenia: From hypothesis-based to susceptibility gene-based models SO BIOLOGICAL PSYCHIATRY LA English DT Review DE schizophrenia; cognition; behavior; genetic; animal; model ID DOPAMINE D1 RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; LYSOSOME-RELATED ORGANELLES; KNOCK-OUT MICE; PREFRONTAL CORTEX; NEUROTROPHIC FACTOR; MUTANT MICE; PREPULSE INHIBITION; DEFICIENT MICE; SUBUNIT GENE AB Translation of human genetic mutations into genetic mouse models is an important strategy to study the pathogenesis of schizophrenia, identify potential drug targets, and test new drugs for new antipsychotic treatments. Although it is impossible to recapitulate the full spectrum of schizophrenia symptoms in animal models, bypothesis-driven genetic mouse models have been successful in reproducing several schizopbrenia-like behaviors and uncovering the roles of specific genes in dopamine and glutamine neurotransmission systems in mediating schizophrenia-like behaviors. Recent discoveries of susceptibility genes for schizophrenia and recognition of cognitive dysfunction as a core feature of schizophrenia and a phenotype of susceptibility for schizophrenia offer opportunities to develop newer genetic mouse models based on susceptibility. This new generation of genetic mouse models could shed light on the etiology of schizophrenia and lead us to new hypotheses, novel diagnostic tools, and more effective therapy. C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Chen, JS (reprint author), NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bldg 10,Room 4N307, Bethesda, MD 20892 USA. EM jingshan.chen@mail.nih.gov RI Lipska, Barbara/E-4569-2017 FU Intramural NIH HHS NR 133 TC 77 Z9 77 U1 1 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2006 VL 59 IS 12 BP 1180 EP 1188 DI 10.1016/j.biopsych.2006.02.024 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 058VI UT WOS:000238692300010 PM 16631133 ER PT J AU Musachio, JL Hong, J Ichise, M Seneca, N Brown, AK Liow, JS Halldin, C Innis, RB Pike, VW He, R Zhou, J Kozikowski, AP AF Musachio, JL Hong, J Ichise, M Seneca, N Brown, AK Liow, JS Halldin, C Innis, RB Pike, VW He, R Zhou, J Kozikowski, AP TI Development of new brain imaging agents based upon nocaine-modafinil hybrid monoamine transporter inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE brain imaging agents; monoamine transporter inhibitors; NET radioligands; DAT radioligands; PET imaging; antidepression ID POSITRON-EMISSION-TOMOGRAPHY; NOREPINEPHRINE TRANSPORTER; DOPAMINE TRANSPORTER; REBOXETINE ANALOGS; PET; BINDING; LIGANDS; COCAINE AB C-11-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsulfanyl]ethanol ([C-11]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3-yl]methylsulfanyl]-1-(piperidin-1-yl)ethanone ([C-11]6) were synthesized and evaluated as new imaging agents for the norepinephrine transporter (NET). [C-11]5 and [C-11]6 display high affinity for the NET in vitro (K-i = 0.94 and 0.68 nM, respectively) and significant selectivity over the dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity and favorable transporter selectivities we speculated that these ligands might serve as useful PET agents for imaging NET in vivo. Contrary to our expectations, both of these ligands provided brain images that were more typical of those shown by agents binding to the DAT. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Drug Discovery Program, Dept Med Chem & Pharmacognosy, Coll Pharm MC781, Chicago, IL 60612 USA. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, Stockholm, Sweden. Acenta Discovery Inc, Tucson, AZ 85747 USA. RP Kozikowski, AP (reprint author), Univ Illinois, Drug Discovery Program, Dept Med Chem & Pharmacognosy, Coll Pharm MC781, 833 S Wood St, Chicago, IL 60612 USA. EM kozikowa@uic.edu FU Intramural NIH HHS; NIDA NIH HHS [DA10458]; NIMH NIH HHS [1R41MH070083, 1R41MH074193] NR 20 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 15 PY 2006 VL 16 IS 12 BP 3101 EP 3104 DI 10.1016/j.bmcl.2006.03.066 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 045SW UT WOS:000237763500002 PM 16621532 ER PT J AU Harding, WW Schmidt, M Tidgewell, K Kannan, P Holden, KG Dersch, CM Rothman, RB Prisinzano, TE AF Harding, WW Schmidt, M Tidgewell, K Kannan, P Holden, KG Dersch, CM Rothman, RB Prisinzano, TE TI Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Selective modification of the furan ring SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE salvinorin A; kappa; opioid; Salvia divinorum; heterocycle ID SALVINORIN-A ANALOGS; OPIOID RECEPTORS; SALVINICIN-B; STEREOCHEMISTRY; AGONIST; POTENT; LIGANDS; C(2) AB A synthetic sequence has been developed to selectively functionalize the furan ring of the natural product salvinorin A (2a). The synthetic routes described convert the furan ring in 2a into an N-sulfonylpyrrole, oxazole or an oxadiazole. In addition, a procedure has been found to remove the furan skeleton completely. Biological results indicate that replacement of the furan ring with an N-sulfonylpyrrole leads to reduced affinity and efficacy at K opioid receptors. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Holden Labs, Carmel, CA 93923 USA. NIDA, Clin Psychopharmacol Sect, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Prisinzano, TE (reprint author), Univ Iowa, Coll Pharm, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM thomas-prisinzano@uiowa.edu RI Prisinzano, Thomas/B-7877-2010; OI Kannan, Pavitra/0000-0002-9170-6062; Tidgewell , Kevin/0000-0002-0501-2604 FU Intramural NIH HHS; NIDA NIH HHS [DA18151, R01 DA018151, R01 DA018151-01A2] NR 35 TC 32 Z9 32 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 15 PY 2006 VL 16 IS 12 BP 3170 EP 3174 DI 10.1016/j.bmcl.2006.03.062 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 045SW UT WOS:000237763500017 PM 16621556 ER PT J AU Ablordeppey, SY Lyles-Eggleston, M Bricker, B Zhang, W Zhu, X Goodman, C Roth, BL AF Ablordeppey, SY Lyles-Eggleston, M Bricker, B Zhang, W Zhu, X Goodman, C Roth, BL TI Evaluation of the eutomer of 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin-1-yl}-1-(4-fluorophenyl)butan- 1-one, {(+)-SYA 09}, a pyrrolidine analog of haloperidol SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE eutomer; enantiomer; haloperidol; analog; antipsychotic; chiral separation; dopamine receptor ligand ID NEUROTOXIC PYRIDINIUM METABOLITE; D-2/D-4 RECEPTOR ANTAGONISTS; IDENTIFICATION; DOPAMINE; SCHIZOPHRENIA; ZIPRASIDONE; DERIVATIVES; PIPERAZINE; INDOLINE; DESIGN AB Enantionteric separation of the racemic 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin-1-yl}-1-(4-fluorophenyl)butan-1-one, a pyrrolidine analog of haloperidol, {(+/-)-SYA 09}, and subsequent binding studies revealed that most of the binding affinity at dopamine and serotonin receptors resides in the (+)-isomer {(+)-SYA 09} or the eutomer. Further pharmacological evaluation of the eutomer revealed that it has a higher affinity for the dopamine D4 (DAD4) receptor subtype (K-i = 3.6 nM) than for the DAD2 subtype (K-i = 51.1 nM) with a ratio of 14.2 (D2K(i)/D4K(i) ratio = 14.2). In an animal model of antipsychotic efficacy, the (+)-SYA 09 was efficacious with an ED50 value of 1.6 mg/kg, ip, and at twice this value, (+)-SYA 09 did not induce significant catalepsy in rats. (c) 2006 Elsevier Ltd. All rights reserved. C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psycoact Drug Screening Program, Cleveland, OH 44106 USA. RP Ablordeppey, SY (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Div Basic Pharmaceut Sci, Tallahassee, FL 32307 USA. EM seth.ablordeppey@famu.edu RI Roth, Bryan/F-3928-2010 FU NCRR NIH HHS [1 C06-RR12512-01, G12 RR 03020]; NIGMS NIH HHS [GM 08111] NR 24 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 15 PY 2006 VL 16 IS 12 BP 3219 EP 3223 DI 10.1016/j.bmcl.2006.03.057 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 045SW UT WOS:000237763500028 PM 16621538 ER PT J AU Schiavo, R Baatar, D Olkhanud, P Indig, FE Restifo, N Taub, D Biragyn, A AF Schiavo, R Baatar, D Olkhanud, P Indig, FE Restifo, N Taub, D Biragyn, A TI Chemokine receptor targeting efficiently directs antigens to MHC class I pathways and elicits antigen-specific CD8(+) T-cell responses SO BLOOD LA English DT Article ID DENDRITIC CELLS; CROSS-PRESENTATION; ANTITUMOR IMMUNITY; PROTECTIVE IMMUNITY; ENDOCYTOSIS; INDUCTION; IMMATURE; CLATHRIN; FUSION; INTERNALIZATION AB Chemokines are key controllers of cell trafficking and are involved in numerous pathologic and inflammatory conditions. However, the fate of a chemokine ligand, once it is enclocytosed with its receptor, remains obscure. Here, using chemokine-tumor antigen fusion constructs, we demonstrate for the first time that chemokines are internalized to early/late endosomal and lysosomal compartments through a clathrin-dependent process and subsequently delivered to the cytosol for proteasomal processing, facilitating efficient cross-presentation to the TAP-1-dependent MHC class I processing pathway. These data not only elucidate the intracellular fate of chemokine ligands upon receptor uptake, but also demonstrate the superior carrier potency of chemokines for delivering self-antigens to both class I and II processing pathways to induce CD8(+) and CD4(+) T-cell responses. C1 NIA, Immunol Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Biragyn, A (reprint author), NIA, Immunol Lab, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM biragyna@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 49 TC 40 Z9 40 U1 0 U2 0 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 JUN 15 PY 2006 VL 107 IS 12 BP 4597 EP 4605 DI 10.1182/blood-2005-08-3207 PG 9 WC Hematology SC Hematology GA 053LA UT WOS:000238305400012 PM 16514063 ER PT J AU Rosenberg, PS Alter, BP Bolyard, AA Bonilla, MA Boxer, LA Cham, B Fier, C Freedman, M Kannourakis, G Kinsey, S Schwinzer, B Zeidler, C Welte, K Dale, DC AF Rosenberg, PS Alter, BP Bolyard, AA Bonilla, MA Boxer, LA Cham, B Fier, C Freedman, M Kannourakis, G Kinsey, S Schwinzer, B Zeidler, C Welte, K Dale, DC CA Severe Chronic Neutropenia Int Reg TI The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy SO BLOOD LA English DT Article ID STIMULATING-FACTOR-RECEPTOR; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; FOLLOW-UP; MUTATIONS; GENE; TRANSFORMATION; AGRANULOCYTOSIS; INTERNALIZATION AB In patients with severe congenital neutropenia (SCN), sepsis mortality is reduced by treatment with granulocyte colony-stimulating factor (G-CSF), but myelodsyplastic syndrome and acute myeloid leukemia (MDS/AML) have been reported. We studied 374 patients with SCN and 29 patients with Shwachman-Diamond syndrome (SDS) on long-term G-CSF enrolled in the Severe Chronic Neutropenia International Registry. In SCN, sepsis mortality was stable at 0.9% per year. The hazard of MDS/AML increased significantly over time, from 2.9% per year after 6 years to 8.0% per year after 12 years on G-CSF After 10 years, the cumulative incidence was 8% for sepsis mortality and 21% for MDS/AML. A subgroup of SCN patients (29%) received more than the median dose of G-CSF ( ! 8 mu g/kg/d), but achieved less than the median absolute neutrophil count (ANC) response (ANC < 2.188 x 10(9)/L [2188/mu L] at 6-18 months). In these less-responsive patients, the cumulative incidence of adverse events was highest: after 10 years, 40% developed MDS/AML and 14% died of sepsis, compared with 11% and 4%, respectively, of more responsive patients whose ANC was above the median on doses of G-CSF below the median. Risk of MDS/AML may be similar in SIDS and SCN. In less-responsive SCN patients, early hematopoietic stem cell transplantation may be a rational option. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Univ Washington, Dept Med, Seattle, WA USA. St Joseph Childrens Hosp, Dept Pediat Hematol Oncol, Paterson, NJ USA. Univ Michigan, Med Ctr, Dept Pediat, Ann Arbor, MI 48109 USA. CancerCare Manitoba, Winnipeg, MB, Canada. Amgen Inc, Boulder, CO USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Ballarat Oncol & Haemotol Serv, Wendouree, Australia. St Jamess Univ Hosp, Leeds, W Yorkshire, England. Hannover Med Sch, Kinderklin, Hannover, Germany. RP Rosenberg, PS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,Execut Plaza S,Rm 8022, Rockville, MD 20852 USA. EM rosenbep@mail.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [1R24AI049392] NR 37 TC 205 Z9 212 U1 2 U2 10 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 JUN 15 PY 2006 VL 107 IS 12 BP 4628 EP 4635 DI 10.1182/blood-2005-11-4370 PG 8 WC Hematology SC Hematology GA 053LA UT WOS:000238305400016 PM 16497969 ER PT J AU Little, RF Pluda, JM Wyvill, KM Rodriguez-Chavez, IR Tosato, G T Catanzaro, A Steinberg, SM Yarchoan, R AF Little, RF Pluda, JM Wyvill, KM Rodriguez-Chavez, IR Tosato, G T Catanzaro, A Steinberg, SM Yarchoan, R TI Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma SO BLOOD LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-12; HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-COUPLED RECEPTOR; CELL STIMULATORY FACTOR; PHASE-I TRIAL; ANTIRETROVIRAL THERAPY; INTERFERON-GAMMA; IFN-GAMMA; CLINICAL-TRIAL; ONCOLOGY-GROUP AB Interleukin-112 (IL-12) enhances Th1-type T-cell responses and exerts antiangiogenic effects. We initiated a phase 1 pilot study of IL-12 in 32 patients with acquired immunodeficiency syndrome (AIDS)-related Kaposi sarcoma (KS) whose KS was progressing while on antiretroviral therapy. Fifteen patients had poor prognosis T1S1 disease. IL-12 was administered subcutaneously twice weekly at doses from 100 to 625 ng/kg. The maximum tolerated dose was 500 ng/kg, and the principal toxicities were flulike symptoms, transaminase or bilirubin elevations, neutropenia, hemolytic anemia, and depression. No tumor responses were seen at the lowest dose (100 ng/kg), but 17 of 24 evaluable patients at the higher doses had partial or complete responses (response rate, 71%; 95% confidence interval, 48%-89%). Only 3 of 17 patients had a change in antiretroviral therapy before responding, and there were no significant differences between responders and nonresponders with regard to changes in CD4 counts or viral loads. Patients had increases in their serum IL-12, interferon-gamma, and inducible protein-10 (IP-10) after the first dose, and increases above baseline persisted after week 4. These results provide preliminary evidence that IL-12 has substantial activity against AIDS-related KS with acceptable toxicity and warrants further investigation for this indication. C1 NCI, Canc Res Ctr, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NIH, Bldg 10,Rm 10S255,MSC 1868, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC006737-14] NR 63 TC 48 Z9 51 U1 1 U2 1 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 JUN 15 PY 2006 VL 107 IS 12 BP 4650 EP 4657 DI 10.1182/blood-2005-11-4455 PG 8 WC Hematology SC Hematology GA 053LA UT WOS:000238305400019 PM 16507779 ER PT J AU Betts, MR Nason, MC West, SM De Rosa, SC Migueles, SA Abraham, J Lederman, MM Benito, JM Goepfert, PA Connors, M Roederer, M Koup, RA AF Betts, MR Nason, MC West, SM De Rosa, SC Migueles, SA Abraham, J Lederman, MM Benito, JM Goepfert, PA Connors, M Roederer, M Koup, RA TI HIV nonprogressors preferentially maintain highly functional HIV-specific CD8(+) T cells SO BLOOD LA English DT Article ID LONG-TERM NONPROGRESSORS; ACTIVE ANTIRETROVIRAL THERAPY; VIRAL LOAD; LYMPHOCYTE RESPONSES; VIRUS-REPLICATION; PRIMARY INFECTION; ESCAPE VARIANTS; VIREMIA; PROLIFERATION; CD4(+) AB Establishing a CD8(+) T cell-mediated immune correlate of protection in HIV disease is crucial to the development of vaccines designed to generate cell-mediated immunity. Historically, neither the quantity nor breadth of the HIV-specific CD8(+) T-cell response has correlated conclusively with protection. Here, we assess the quality of the HIV-specific CD8(+) T-cell response by measuring 5 CD8(+) T-cell functions (degranulation, IFN-gamma, MIP-1 beta, TNF-alpha, and IL-2) simultaneously in chronically HIV-Infected individuals and elite nonprogressors. We find that the functional profile of HIV-specific CD8(+) T cells in progressors is limited compared to that of nonprogressors, who consistently maintain highly functional CD8(+) T cells. This limited functionality is independent of HLA type and T-cell memory phenotype, is HIV-specific rather than generalized, and is not effectively restored by therapeutic intervention. Whereas the total HIV-specific CD8(+) T-cell frequency did not correlate with viral load, the frequency and proportion of the HIV-specific T-cell response with highest functionality inversely correlated with viral load in the progressors. Thus, rather than quantity or phenotype, the quality of the CD8(+) T-cell functional response serves as an immune correlate of HIV disease progression and a potential qualifying factor for evaluation of HIV vaccine efficacy. C1 NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Med, Ctr AIDS Res, Cleveland, OH 44106 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Hosp Carlos III, Dept Infect Dis, Madrid, Spain. RP Koup, RA (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, 40 Convent Dr,Rm 3502, Bethesda, MD 20892 USA. EM betts@mail.med.upenn.edu; rkoup@mail.nih.gov FU NIAID NIH HHS [AI 36219, AI 49126] NR 34 TC 1103 Z9 1127 U1 11 U2 46 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 JUN 15 PY 2006 VL 107 IS 12 BP 4781 EP 4789 DI 10.1182/blood-2005-12-4818 PG 9 WC Hematology SC Hematology GA 053LA UT WOS:000238305400038 PM 16467198 ER PT J AU Sauer, I Schaljo, B Vogl, C Gattermeier, I Kolbe, T Muller, M Blackshear, PJ Kovarik, P AF Sauer, I Schaljo, B Vogl, C Gattermeier, I Kolbe, T Muller, M Blackshear, PJ Kovarik, P TI Interferons limit inflammatory responses by induction of tristetraprolin SO BLOOD LA English DT Article ID ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; ALPHA MESSENGER-RNA; AU-RICH ELEMENTS; IFN-GAMMA; GENE-EXPRESSION; MAP KINASE; TNF-ALPHA; TRANSCRIPTIONAL REGULATION; SERINE PHOSPHORYLATION AB Interferons (IFNs) are cytokines with pronounced proinflammatory properties. Here we provide evidence that IFNs also play a key role in decline of inflammation by inducing expression of tristetraprolin (Ttp). TTP is an RNA-binding protein that destabilizes several AU-rich element-containing mRNAs including TNF alpha. By promoting mRNA decay, TTP significantly contributes to cytokine homeostasis. Now we report that IFNs strongly stimulate expression of TTP if a costimulatory stress signal is provided. IFIN-induced expression of Ttp depends on the IFN-activated transcription factor STAT1, and the costimulatory stress signal requires p38 MAPK. Within the Ttp promoter we have identified a functional gamma interferon-activated sequence that recruits STAT1. Consistently, STAT1 is required for full expression of Ttp in response to LPS that stimulates both p38 MAPK and, indirectly, interferon signaling. We demonstrate that in macrophages IFN-induced TTP protein limits LPS-stimulated expression of several proinflarnmatory genes, such as TNF alpha, IL-6, Ccl2, and Ccl3. Thus, our findings establish a link between interferon responses and TTP-mediated mRNA decay during inflammation, and propose a novel immunomodulatory role of IFNs. C1 Univ Vienna, Dept Microbiol & Immunobiol, A-1030 Vienna, Austria. Vienna Univ Vet Med, Inst Genet & Anim Breeding, Vienna, Austria. Vienna Univ Vet Med, Austrian Ctr Biomodelling & Transgenet, Vienna, Austria. IFA, Interuniv Res Ctr, Dept Agrobiotechnol, Tulln, Austria. Univ Nat Resources & Appl Life Sci, Vienna, Austria. NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA. RP Kovarik, P (reprint author), Univ Vienna, Dept Microbiol & Immunobiol, Dr Bohr Gasse 9, A-1030 Vienna, Austria. EM pavel.kovarik@univie.ac.at RI Kovarik, Pavel/D-1184-2014 OI Kovarik, Pavel/0000-0003-2956-0944 FU Austrian Science Fund FWF [F 2805] NR 55 TC 88 Z9 90 U1 1 U2 6 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 JUN 15 PY 2006 VL 107 IS 12 BP 4790 EP 4797 DI 10.1182/blood-2005-07-3058 PG 8 WC Hematology SC Hematology GA 053LA UT WOS:000238305400039 PM 16514065 ER PT J AU Hoelbl, A Kovacic, B Kerenyi, MA Simma, O Warsch, W Cui, YZ Beug, H Hennighausen, L Moriggl, R Sexl, V AF Hoelbl, A Kovacic, B Kerenyi, MA Simma, O Warsch, W Cui, YZ Beug, H Hennighausen, L Moriggl, R Sexl, V TI Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PERIPHERAL T-CELLS; BCR-ABL; CONSTITUTIVE ACTIVATION; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; SIGNAL TRANSDUCER; GAMMA LOCUS; IN-VIVO; PROTEINS AB The Stat5 transcription factors Stat5a and Stat5b have been implicated in lymphoid development and transformation. Most studies have employed Stat5a/b-deficient mice where gene targeting disrupted the first protein-coding exon, resulting in the expression of N-terminally truncated forms of Stat5a/b (Stat5a/b(Delta N/Delta N) mice). We have now reanalyzed lymphoid development in Stat5a/b(null/null) mice having a complete deletion of the Stat5a/b gene locus. The few surviving Stat5a/b(null/null) mice lacked CD8(+) T lymphocytes. A massive reduction of CD8(+) T cells was also found in Stat5a/b(fl/fl) Ick-cre transgenic animals. While gamma delta T-cell receptor-positive (gamma delta TCR+) cells were expressed at normal levels in Stat5a/b(Delta N/Delta N) mice, they were completely absent in Stat5a/b(null/null) animals. Moreover, B-cell maturation was abrogated at the pre-pro-B-cell stage in Stat5a/b(null/null) mice, whereas Stat5a/b(Delta N/Delta N) B-lymphoid cells developed to the early pro-B-cell stage. In vitro assays using fetal liver-cell cultures confirmed this observation. Most strikingly, Stat5a/b(null/null) cells were resistant to transformation and leukemia development induced by Abelson oncogenes, whereas Stat5a/b(Delta N/Delta N)-derived cells readily transformed. These findings show distinct lymphoid defects for Stat5a/b(Delta N/Delta N) and Stat5a/b(null/null) mice and define a novel functional role for the N-termini of Stat5a/b in B-lymphoid transformation. C1 Med Univ Vienna, Dept Pharmacol, Inst Pharmacol, A-1090 Vienna, Austria. Med Univ Vienna, Dept Pharmacol, Max F Perutz Labs, A-1090 Vienna, Austria. Inst Mol Pathol, A-1030 Vienna, Austria. NIH, Lab Genet & Physiol, Bethesda, MD 20892 USA. Ludwig Boltzmann Inst Canc Res, Vienna, Austria. RP Sexl, V (reprint author), Med Univ Vienna, Dept Pharmacol, Inst Pharmacol, Wahringerstr 13A, A-1090 Vienna, Austria. EM veronika.sexl@meduniwien.ac.at RI Kovacic, Boris/J-1871-2016; OI Kovacic, Boris/0000-0002-1148-4149; Hoelbl-Kovacic, Andrea/0000-0001-6219-8794; Moriggl, Richard/0000-0003-0918-9463 FU Austrian Science Fund FWF [F 2810, F 2801, F 2802, F 2807] NR 57 TC 122 Z9 124 U1 0 U2 0 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 JUN 15 PY 2006 VL 107 IS 12 BP 4898 EP 4906 DI 10.1182/blood-2005-09-3596 PG 9 WC Hematology SC Hematology GA 053LA UT WOS:000238305400052 PM 16493008 ER PT J AU Doody, MM Freedman, DM Alexander, BH Hauptmann, M Miller, JS Rao, RS Mabuchi, K Ron, E Sigurdson, AJ Linet, MS AF Doody, MM Freedman, DM Alexander, BH Hauptmann, M Miller, JS Rao, RS Mabuchi, K Ron, E Sigurdson, AJ Linet, MS TI Breast cancer incidence in US radiologic technologists SO CANCER LA English DT Article DE breast cancer; ionizing radiation; radiation-induced neoplasms; radiologic technologists; epidemiology; cohort studies ID ATOMIC-BOMB SURVIVORS; X-RAY WORKERS; RADIATION EXPOSURE; FLUOROSCOPY COHORT; UNITED-STATES; RISK; MORTALITY; CHINA; STAFF AB BACKGROUND. Studies of atomic bomb survivors and medically exposed populations have demonstrated an increased risk of breast cancer associated with acute or protracted, intermediate-dose or high-dose, ionizing radiation; however, the risks associated with low-dose and low-dose-rate (protracted) exposures are less certain. METHODS. The authors evaluated incident breast cancer risks from 1983 to 1998 according to employment characteristics and a 4-level proxy index for cumulative radiation exposure based on 2 mail surveys among 56,436 U.S. female radiologic technologists who were certified from 1925 to 1980, adjusting for established breast cancer risk factors. RESULTS. During follow-up, 1050 new breast cancer diagnoses were ascertained. Compared with radiologic technologists who began working in 1970 or later, adjusted breast cancer risks for those who first worked in the 1960s, 1950s, 1940s, from 1935 to 1939, and before 1935 were 1.0 (95% confidence interval [CI], 0.8-1.2), 1.2 (95% CI, 0.9-1.6), 1.0 (95% CI, 0.7-1.5), 1.8 (95% CI, 1.0-3.2), and 2.9 (95% CI, 1.3-6.2), respectively. The risk rose with the number of years worked before 1940 (P value for trend = .002) and was elevated significantly among those who began working before age 17 years (relative risk, 2.6; 95% CI, 1.3-5.1; 10 women) but was not related to the total years worked in the 1940s or later. Compared with technologists who had a Level 1 (minimal) proxy index for cumulative radiation exposure, breast cancer risks were 1.0 (95% CL 0.9-1.2), 1.0 (95% CI, 0.7-1.3), and 1.5 (95% CI, 1.0-2.2), respectively, for technologists who had Level 2, Level 3, and Level 4 (highest) exposure. CONCLUSIONS. Breast cancer risk was elevated significantly in female radiologic technologists who experienced daily low-dose radiation exposures over several years that potentially resulted in appreciable cumulative exposure. The increased risk for total years worked before 1940, but not later, was consistent with decreasing occupational radiation exposures, improvements in radiation technology, and more stringent radiation protection standards over time. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA. Informat Management Serv Inc, Rockville, MD USA. RP Doody, MM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7040, Bethesda, MD 20892 USA. EM doodym@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CP-51016, N01-CP-15673, N02-CP-81005, N02-CP-81121] NR 46 TC 39 Z9 40 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2006 VL 106 IS 12 BP 2707 EP 2715 DI 10.1002/cncr.21876 PG 9 WC Oncology SC Oncology GA 051OR UT WOS:000238170900025 PM 16639729 ER PT J AU Gu, J Wu, XF Dong, Q Romeo, MJ Lin, X Gutkind, JS Berman, DM AF Gu, J Wu, XF Dong, Q Romeo, MJ Lin, X Gutkind, JS Berman, DM TI A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans SO CANCER LA English DT Article DE PDZ-Rho guanine nucleotide exchange factors; regulator of G-protein signaling; lung cancer; single nucleotide polymorphisms ID FAMILY GTPASES; G-PROTEINS; LEUKEMIA; LARG; EXPRESSION; RECEPTOR; SMOKERS; PHASE AB BACKGROUND. Based on in vitro studies, Rho guanine nucleotide exchange factors (RhoGEFs) are key regulators of mitogenic and transforming pathways. At least I family member, PDZ-RhoGEF, also integrates signaling between monomeric Rho G proteins and heterotrimeric G proteins through a so-called regulator of G-protein signaling (RGS) domain. Recently, the authors reported that 3 single-nucleotide polymorphisms (SNPs) in 2 members of the RGS family were associated with significant reductions in the risk of cancer. METHODS. For the current report, the authors studied the risk of lung cancer associated with a nonsynonymous SNP (rs868188; Ser1416Gly) in PDZ-RhoGEF in a large lung cancer case-control study of 2260 Caucasians and 369 Mexican Americans. RESULTS. Compared with individuals who had the wild-type genotype (AA), Mexican Americans with the variant genotypes (AG and GG) had a significantly reduced risk for lung cancer (odds ratio [OR], 0.57; 95% confidence interval [95%CI], 0.34-0.94). The protective effect appeared to be more evident in younger individuals (OR, 0.42; 95%CI, 0.20-0.91), men (OR, 0.36; 95%CI, 0.18-0.71), and ever smokers (OR, 0.50; 95%CI, 0.29-0.88). A joint effect was observed between Ser1416Gly and polymorphisms in 2 cell-cycle control genes: p53 (intron 3) and cyclin D1 (CCND1). Tallying the variant alleles of the 4 RGS gene SNPs, a gene-dosage effect was apparent. Compared with individuals who had < 3 variant alleles, patients with >= 3 variant alleles had a 51% reduction in lung cancer risk (OR, 0.49; 95%CI, 0.28-0.88). CONCLUSIONS. To the authors' knowledge, this is the first epidemiological study to link PDZ-RhoGEF polymorphisms with cancer risk. The results suggest that there are interactions between RGS2, RGS6, and PDZ-RhoGEF and validate this family of proteins as key regulators of tumorigenesis. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Berman, DM (reprint author), Bristol Myers Squibb Co, Clin Discovery Oncol, E-1302,Route 206,Provinceline Rd, Princeton, NJ 08540 USA. EM bermand@mail.nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [CA86390, CA 74880, CA55769, CA68437] NR 31 TC 17 Z9 17 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2006 VL 106 IS 12 BP 2716 EP 2724 DI 10.1002/cncr.21944 PG 9 WC Oncology SC Oncology GA 051OR UT WOS:000238170900026 PM 16691626 ER PT J AU Shen, WH Wang, JL Wu, JJ Zhurkin, VB Yin, YX AF Shen, WH Wang, JL Wu, JJ Zhurkin, VB Yin, YX TI Mitogen-activated protein kinase phosphatase 2: A novel transcription target of p53 in apoptosis SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; MAP KINASE; OXIDATIVE STRESS; PATHWAY; GENES; INVOLVEMENT; GROWTH; CANCER AB The p53 tumor suppressor plays critical roles in diverse cellular responses such as cell cycle arrest, senescence, and apoptosis through transcriptional control of its target genes. Identification and characterization of new p53 target genes will advance our understanding of how p53 exerts its multiple regulatory functions. In this article, we show that mitogen-activated protein kinase phosphatase 2 (MIKP2) is a novel transcription target of p53 in mediating apoptosis. Moreover, we identify a 10-bp perfect palindrome motif (CTGGCGCCAG) in the MKP2 promoter as a new binding site for p53 to activate the MKP2 gene. This GC-rich palindrome is completely different from the consensus p53 binding sequence. Induction of MKP2 is highly responsive to oxidative stress in a p53-dependent manner. Interestingly, the p53-dependent induction of MKP2 is prominent only in the cellular response to stimuli leading to apoptosis but not to cell cycle arrest. In response to oxidative stress, MKP2 is not only required for p53-mediated apoptosis, but ectopic MKP2 expression can also enhance apoptotic responses even independent of p53. These data suggest that p53 regulates distinct genes via different binding mechanisms and that MKP2 is an essential target of p53 in signaling apoptosis. C1 Columbia Univ Coll Phys & Surg, Dept Radiat Oncol, Coll Phys & Surg, New York, NY 10032 USA. NCI, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. RP Yin, YX (reprint author), Columbia Univ Coll Phys & Surg, Dept Radiat Oncol, Coll Phys & Surg, 630 W 168th St,VC11-213,630 W 168th St, New York, NY 10032 USA. EM yy151@columbia.edu OI SHEN, WEN/0000-0002-5830-6518 FU NCI NIH HHS [CA73946] NR 24 TC 34 Z9 34 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2006 VL 66 IS 12 BP 6033 EP 6039 DI 10.1157/0008-5472.CAN-05-3878 PG 7 WC Oncology SC Oncology GA 054LX UT WOS:000238379500012 PM 16778175 ER PT J AU Nam, JS Suchar, AM Kang, MJ Stuelten, CH Tang, BW Michalowska, AM Fisher, LW Fedarko, NS Jain, A Pinkas, J Lonning, S Wakefield, LM AF Nam, JS Suchar, AM Kang, MJ Stuelten, CH Tang, BW Michalowska, AM Fisher, LW Fedarko, NS Jain, A Pinkas, J Lonning, S Wakefield, LM TI Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer SO CANCER RESEARCH LA English DT Article ID INTEGRIN-BINDING LIGAND; TGF-BETA; MAMMARY-TUMOR; ANTITUMOR-ACTIVITY; FACTOR (TGF)-BETA; LUNG-CANCER; EXPRESSION; METASTASIS; GENE; OSTEOPONTIN AB Transforming growth factor beta s (TGF-beta) play a dual role in carcinogenesis, functioning as tumor suppressors early in the process, and then switching to act as prometastatic factors in late-stage disease. We have previously shown that high molecular weight TGF-beta antagonists can suppress metastasis without the predicted toxicities. To address the underlying mechanisms, we have used the 4T1 syngeneic mouse model of metastatic breast cancer. Treatment of mice with a monoclonal anti-TGF-beta antibody (1D11) significantly suppressed metastasis of 4T1 cells to the lungs, When metastatic 4T1 cells were recovered from lungs of 1D11-treated and control mice, the most differentially expressed gene was found to be bone sialoprotein (Bsp). Immunostaining confirmed the loss of Bsp protein in 1D11-treated lung metastases, and TGF-beta was shown to regulate and correlate with Bsp expression in vitro. Functionally, knockdown of Bsp in 4T1 cells reduced the ability of TGF-beta to induce local collagen degradation and invasion in vitro, and treatment with recombinant Bsp protected 4T1 cells from complement-mediated lysis. Finally, suppression of Bsp in 4T1 cells reduced metastasis in vivo. We conclude that Bsp is a plausible mediator of at least some of the tumor cell-targeted prometastatic activity of TGF-beta in this model and that Bsp expression in metastases can be successfully suppressed by systemic treatment with anti-TGF-beta antibodies. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. Johns Hopkins Univ, Dept Med, Div Geriatr, Baltimore, MD USA. Genzyme Corp, Framingham, MA 01701 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Room C629,Bldg 41,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. EM wakefiel@dce41.nci.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005785-11] NR 48 TC 65 Z9 70 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2006 VL 66 IS 12 BP 6327 EP 6335 DI 10.1158/0008-5472.CAN-06-0068 PG 9 WC Oncology SC Oncology GA 054LX UT WOS:000238379500047 PM 16778210 ER PT J AU Gore, SD Baylin, S Sugar, E Carraway, H Miller, CB Carducci, M Grever, M Galm, O Dauses, T Karp, JE Rudek, MA Zhao, M Smith, BD Manning, J Jiemjit, A Dover, G Mays, A Zwiebel, J Murgo, A Weng, LJ Herman, JG AF Gore, SD Baylin, S Sugar, E Carraway, H Miller, CB Carducci, M Grever, M Galm, O Dauses, T Karp, JE Rudek, MA Zhao, M Smith, BD Manning, J Jiemjit, A Dover, G Mays, A Zwiebel, J Murgo, A Weng, LJ Herman, JG TI Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol ID ORAL SODIUM PHENYLBUTYRATE; LOW-DOSE 5-AZA-2'-DEOXYCYTIDINE; RISK MYELODYSPLASTIC SYNDROME; CYTIDINE DEAMINASE GENE; CPG ISLAND METHYLATION; ARA-C SENSITIVITY; HYPOMETHYLATING AGENT; COLORECTAL-CANCER; ELDERLY-PATIENTS; ACUTE-LEUKEMIA AB Optimal reexpression of most genes silenced through promoter methylation requires the sequential application of DNA methyltransferase inhibitors followed by histone deacetylase inhibitors in tumor cell cultures. Patients with myelodysplastic syndrome or acute myeloid leukemia (AML) were treated with the methyltransferase inhibitor 5-azacitidine (aza-CR) followed by the histone deacetylase inhibitor sodium phenylbutyrate. Major responses associated with cytogenetic complete response developed in patients receiving prolonged dosing schedules of aza-CR. Bisulfite sequencing of the p-15 promoter in marrow DNA during the first cycle of treatment showed heterogeneous allelic demethylation in three responding patients, suggesting ongoing demethylation within the tumor clone, but no demethylation in two nonresponders. Six of six responding patients with pretreatment methylation of p15 or CDH-1 promoters reversed methylation during the first cycle of therapy (methylation-specific PCR), whereas none of six nonresponders showed any demethylation. Gene demethylation correlated with the area under the aza-CR plasma concentration-time curve. Administration of both drugs was associated with induction of acetylation of histories H3 and H4. This study provides the first demonstration that molecular mechanisms responsible for responses to DNA methyltransferase/histone deacetylase inhibitor combinations may include reversal of aberrant epigenetic gene silencing. The promising percentage of major hematologic responses justifies the testing of such combinations in prospective randomized trials. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA. Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA. Univ Klinikum Aachen, Rhein Westfal TH Aachen, Med Klin 4, Aachen, Germany. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Gore, SD (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St, Baltimore, MD 21287 USA. EM gorest@jhmi.edu FU NCI NIH HHS [K24 CA11717, P30 CA06973, R01 CA087760, R01 CA87760, U01 CA70095] NR 48 TC 340 Z9 356 U1 0 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2006 VL 66 IS 12 BP 6361 EP 6369 DI 10.1158/0008-5472.CAN-06-0080 PG 9 WC Oncology SC Oncology GA 054LX UT WOS:000238379500051 PM 16778214 ER PT J AU Dmitrieva, NI Ferraris, JD Norenburg, JL Burg, MB AF Dmitrieva, NI Ferraris, JD Norenburg, JL Burg, MB TI The saltiness of the sea breaks DNA in marine invertebrates - Possible implications for animal evolution SO CELL CYCLE LA English DT Article DE NaCl; DNA damage; evolution; cambrian explosion; osmoregulation; marine invertabrates ID MURINE KIDNEY-CELLS; CAMBRIAN EXPLOSION; HIGH NACL; HYPEROSMOLALITY; STRESS; SALT; UREA AB More than 97 percent of the world's water is ocean and its average osmolality of 1000 mosmol/kg is much higher than the 300 mosmol/kg found in most of the intercellular fluids of vertebrates. Many marine invertebrates are osmoconformers, meaning that the osmolality of their extracellular fluid is the same as that of seawater. We report here that marine invertebrates from diverse phyla have numerous DNA breaks in their cells while they are exposed to normal seawater containing high NaCl, but that the DNA breaks decrease or disappear when the animals are acclimated to the same water diluted to 300 mosmol/kg. We speculate that, since DNA breaks cause mutations, salinity might have important background effects on the rate and course of evolution. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Smithsonian Natl Museum Nat Hist, Dept Invertebrate Zool, Washington, DC USA. RP Dmitrieva, NI (reprint author), 9000 Rockville Pike,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM dmitrien@nhlbi.nih.gov RI Dmitrieva, Natalia/A-2924-2013; Norenburg, Jon/K-3481-2015 OI Dmitrieva, Natalia/0000-0001-8074-6950; Norenburg, Jon/0000-0001-7776-1527 FU Intramural NIH HHS NR 24 TC 14 Z9 14 U1 2 U2 10 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2006 VL 5 IS 12 BP 1320 EP 1323 DI 10.4161/cc.5.12.2867 PG 4 WC Cell Biology SC Cell Biology GA 057FH UT WOS:000238581200016 PM 16775417 ER PT J AU Deb-Basu, D Aleem, E Kaldis, P Felsher, DW AF Deb-Basu, Debabrita Aleem, Eiman Kaldis, Philipp Felsher, Dean W. TI CDK2 is required by MYC to induce apoptosis SO CELL CYCLE LA English DT Article DE MYC; CDK2; apoptosis; Cyclin E; p27 ID CELL-CYCLE ARREST; BCL-X-L; C-MYC; CANCER-CELLS; NEOPLASTIC PHENOTYPE; MEDIATED APOPTOSIS; GENE AMPLIFICATION; TUMOR-SUPPRESSOR; KINASE-ACTIVITY; P53 AB Depending upon the cellular and physiologic context, the overexpression of the MYC proto-oncogene results in rapid cell growth, proliferation, induction of apoptosis and/or proliferative arrest. What determines the precise consequences upon MYC activation is not clear. We have found that cyclin-dependent kinase 2 (CDK2) is required by MYC to induce apoptosis. MYC-induced apoptosis was suppressed in mouse embryonic fibroblasts (MEF) knocked out for Cdk2 or normal human fibroblasts (NHF) upon expression of the CDK2 inhibitor p27 or treated with RNAi directed at CDK2. Knockout of Cdk2 did not prevent MYC from inducing p53 and Bim. The inhibition of CDK2 did not prevent apoptosis induced by the DNA damaging agent etoposide. Our results surprisingly suggest that CDK2 defines whether MYC induction causes apoptosis. C1 Stanford Univ, Div Oncol, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Felsher, DW (reprint author), Stanford Univ, Div Oncol, Dept Med, 269 Campus Dr, Stanford, CA 94305 USA. EM dfelsher@leland.stanford.edu RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213 FU NCI NIH HHS [1R01 CA105102, 1R01 CA89305-01A1, 3R01 CA89305-0351, T32 CA09151] NR 59 TC 15 Z9 17 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2006 VL 5 IS 12 BP 1342 EP 1347 DI 10.4161/cc.5.12.2859 PG 6 WC Cell Biology SC Cell Biology GA 057FH UT WOS:000238581200019 PM 16760655 ER PT J AU Peruzzi, B Bottaro, DP AF Peruzzi, B Bottaro, DP TI Targeting the c-Met signaling pathway in cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; PAPILLARY RENAL-CARCINOMAS; RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER; SOMATIC MUTATIONS; MONOCLONAL-ANTIBODIES; LIVER-REGENERATION; ANTITUMOR-ACTIVITY; STRUCTURAL BASIS; POINT MUTATIONS AB On binding to the cell surface receptor tyrosine kinase (TK) known as c-Met, hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets including, epithelial and endothelial cells, hematopoietic cells, neurons, melanocytes, and hepatocytes. These pleiotropic actions are fundamentally important during development, homeostasis, and tissue regeneration. HGF signaling also contributes to oncogenesis and tumor progression in several human cancers and promotes aggressive cellular invasiveness that is strongly linked to tumor metastasis. Our present understanding of c-Met oncogenic signaling supports at least three avenues of pathway selective anticancer drug development: antagonism of ligand/receptor interaction, inhibition of TK catalytic activity, and blockade of intracellular receptor/effector interactions. Potent and selective preclinical drug candidates have been developed using all three strategies, and human clinical trials in two of the three areas are now under way. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10,CRC 1,W Room 3961,10 Ctr Dr MSC 1107, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU Intramural NIH HHS NR 56 TC 265 Z9 276 U1 2 U2 11 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 JUN 15 PY 2006 VL 12 IS 12 BP 3657 EP 3660 DI 10.1158/1078-0432.CCR-06-0818 PG 4 WC Oncology SC Oncology GA 054YS UT WOS:000238415100005 PM 16778093 ER PT J AU Kelloff, GJ Lippman, SM Dannenberg, AJ Sigman, CC Pearce, HL Reid, BJ Szabo, E Jordan, VC Spitz, MR Mills, GB Papadimitrakopoulou, VA Lotan, R Aggarwal, BB Bresalier, RS Kim, J Arun, B Lu, KH Thomas, ME Rhodes, HE Brewer, MA Follen, M Shin, DM Parnes, HL Siegfried, JM Evans, AA Blot, WJ Chow, WH Blount, PL Maley, CC Wang, KK Lam, S Lee, JJ Dubinett, SM Engstrom, PF Meyskens, FL O'Shaughnessy, J Hawk, ET Levin, B Nelson, WG Hong, WK AF Kelloff, GJ Lippman, SM Dannenberg, AJ Sigman, CC Pearce, HL Reid, BJ Szabo, E Jordan, VC Spitz, MR Mills, GB Papadimitrakopoulou, VA Lotan, R Aggarwal, BB Bresalier, RS Kim, J Arun, B Lu, KH Thomas, ME Rhodes, HE Brewer, MA Follen, M Shin, DM Parnes, HL Siegfried, JM Evans, AA Blot, WJ Chow, WH Blount, PL Maley, CC Wang, KK Lam, S Lee, JJ Dubinett, SM Engstrom, PF Meyskens, FL O'Shaughnessy, J Hawk, ET Levin, B Nelson, WG Hong, WK CA AACR Task Force Canc Prevention TI Progress in chemoprevention drug development: The promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer - A plan to move forward SO CLINICAL CANCER RESEARCH LA English DT Review ID GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; HIGH-GRADE DYSPLASIA; 2ND PRIMARY TUMORS; NONSTEROIDAL ANTIINFLAMMATORY DRUG; SURGICAL ADJUVANT BREAST; SURROGATE END-POINTS; CHRONIC HEPATITIS-C; UPPER-AERODIGESTIVE-TRACT; PLACEBO-CONTROLLED TRIAL AB This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education. C1 NCI, Rockville, MD 20852 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cornell Univ, Weill Med Coll, New York, NY USA. CCS Associates, Mountain View, CA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Arizona, Tucson, AZ USA. Emory Univ, Atlanta, GA 30322 USA. Univ Pittsburgh, Pittsburgh, PA USA. Int Epidemiol Inst, Rockville, MD USA. Mayo Clin, Rochester, MN USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif Irvine, Irvine, CA USA. Texas Oncol PA, US Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. Johns Hopkins Univ, Baltimore, MD USA. RP Kelloff, GJ (reprint author), NCI, Execut Plaza N,Room 6058,6130 Execut Blvd, Rockville, MD 20852 USA. EM kelloffg@mail.nih.gov RI Ray, Dana/C-3470-2013; Aggarwal, Bharat/G-3388-2013; Jordan, V. Craig/H-4491-2011 NR 416 TC 190 Z9 193 U1 2 U2 11 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 JUN 15 PY 2006 VL 12 IS 12 BP 3661 EP 3697 DI 10.1158/1078-0432.CCR-06-1104 PG 37 WC Oncology SC Oncology GA 054YS UT WOS:000238415100006 PM 16778094 ER PT J AU Difeo, A Narla, G Hirshfeld, J Camacho-Vanegas, O Narla, J Rose, SL Kalir, T Yao, S Levine, A Birrer, MJ Bonome, T Friedman, SL Buller, RE Martignetti, JA AF Difeo, A Narla, G Hirshfeld, J Camacho-Vanegas, O Narla, J Rose, SL Kalir, T Yao, S Levine, A Birrer, MJ Bonome, T Friedman, SL Buller, RE Martignetti, JA TI Roles of KLF6 and KLF6-SV1 in ovarian cancer progression and intraperitoneal dissemination SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; TRANSCRIPTION FACTOR KLF6; KRUPPEL-LIKE FACTOR-6; CELL LUNG-CANCER; PROSTATE-CANCER; CLEAR-CELL; EXPRESSION; INHIBITION; ANGIOGENESIS AB Purpose: We investigated the role of the KLF6 tumor suppressor gene and its alternatively spliced isoform KLF6-SV1 in epithelial ovarian cancer (EOC). Experimental Design: We first analyzed tumors from 68 females with EOC for KLF6 gene inactivation using fluorescent loss of heterozygosity (LOH) analysis and direct DNA sequencing and then defined changes in KLF6 and KLF6-SV1 expression levels by quantitative real-time PCR. We then directly tested the effect of KLF6 and KLF6-SV1 inhibition in SKOV-3 stable cell lines on cellular invasion and proliferation in culture and tumor growth, i.p. dissemination, ascites production, and angiogenesis in vivo using BALB/c nu/nu mice. All statistical tests were two sided. Results: LOH was present in 59% of samples in a cell type-specific manner, highest in serous (72%) and endometrioid (75%) subtypes, but absent in clear cell tumors. LOH was significantly correlated with tumor stage and grade. In addition, KLF6 expression was decreased in tumors when compared with ovarian surface epithelial cells. In contrast, KLF6-SV1 expression was increased similar to 5-fold and was associated with increased tumor grade regardless of LOH status. Consistent with these findings, KLF6 silencing increased cellular and tumor growth, angiogenesis, and vascular endothelial growth factor expression, i.p. dissemination, and ascites production. Conversely, KLF6-SV1 down-regulation decreased cell proliferation and invasion and completely suppressed in vivo tumor formation. Conclusion: Our results show that KLF6 and KLF6-SV1 are associated with key clinical features of EOC and suggest that their therapeutic targeting may alter ovarian cancer growth, progression, and dissemination. C1 Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. Reg Med Ctr, Dept Pathol, San Jose, CA USA. Univ Iowa Hosp & Clin, Div Gynecol Oncol, Iowa City, IA 52242 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Martignetti, JA (reprint author), Mt Sinai Sch Med, Dept Human Genet, 1425 Madison Ave,Box 1498, New York, NY 10029 USA. EM John.Martignetti@mssm.edu NR 40 TC 64 Z9 65 U1 0 U2 3 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 JUN 15 PY 2006 VL 12 IS 12 BP 3730 EP 3739 DI 10.1158/1078-0432.CCR-06-0054 PG 10 WC Oncology SC Oncology GA 054YS UT WOS:000238415100012 PM 16778100 ER PT J AU Piekarz, RL Frye, AR Wright, JJ Steinberg, SM Liewehr, DJ Rosing, DR Sachdev, V Fojo, T Bates, SE AF Piekarz, RL Frye, AR Wright, JJ Steinberg, SM Liewehr, DJ Rosing, DR Sachdev, V Fojo, T Bates, SE TI Cardiac studies in patients treated with depsipeptide, FK228, in a phase II trial for T-cell lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; LEFT-VENTRICULAR FUNCTION; QT INTERVAL; TROPONIN-I; INDUCED CARDIOTOXICITY; CLINICAL-TRIALS; FR901228; ACETYLATION; HYPERTROPHY; DYSFUNCTION AB Purpose: The histone deacetylase inhibitor depsipeptide (FK228) has activity in patients with cutaneous or peripheral T-cell lymphoma. Electrocardiogram abnormalities, thought to be a class effect, were observed in preclinical animal studies and phase I testing and led to the incorporation of intensive cardiac monitoring in an ongoing efficacy trial. Patients and Methods: This report summarizes the cardiac monitoring of 42 patients enrolled and treated on a phase II trial with depsipepticle. Cardiac evaluations included serial electrocardiograms to evaluate T-wave, ST segment, and QT interval effects and serial serum cardiac troponin I levels and left ventricular ejection fraction (LVEF) evaluations to exclude myocardial damage. Results: Cardiac studies from 282 cycles and 736 doses of depsipepticle included 2,051 electrocardiograms and 161 LVEF evaluations. Although T-wave flattening (grade 1) or ST segment depression (grade 2) was observed in more than half of the electrocardiograms obtained posttreatment, these electrocardiogram abnormalities were not associated with elevation of cardiac troponin I or with altered left ventricular function. No significant changes in LVEF were observed, even in 16 patients treated for >= 6 months and regardless of prior anthracycline exposure. Posttreatment electrocardiograms had a mean heart rate-corrected QT interval prolongation of 14.4 milliseconds compared with baseline. Electrolyte replacement has been instituted to mitigate potential untoward effects. Conclusion: The data obtained in this study show that the administration of depsipepticle is not associated with myocardial damage or impaired cardiac function. The potential effect of heart rate-corrected QT interval prolongation remains under study. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapeut Evaluat Program, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Piekarz, RL (reprint author), NCI, Ctr Canc Res, NIH, Room 12N226,Bldg 10,10 Ctr Dr MSC 1903, Bethesda, MD 20892 USA. EM rpiekarz@nih.gov FU Intramural NIH HHS NR 55 TC 158 Z9 164 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 JUN 15 PY 2006 VL 12 IS 12 BP 3762 EP 3773 DI 10.1158/1078-0432.CCR-05-2095 PG 12 WC Oncology SC Oncology GA 054YS UT WOS:000238415100016 PM 16778104 ER PT J AU Zhao, WL Chuang, EY Mishra, M Awwad, R Bisht, K Sun, LC Nguyen, P Pennington, JD Wang, TJC Bradbury, CM Huang, L Chen, ZJ Bar-Sela, G Robbins, MEC Gius, D AF Zhao, WL Chuang, EY Mishra, M Awwad, R Bisht, K Sun, LC Nguyen, P Pennington, JD Wang, TJC Bradbury, CM Huang, L Chen, ZJ Bar-Sela, G Robbins, MEC Gius, D TI Distinct effects of ionizing radiation on in vivo murine kidney and brain normal tissue gene expression SO CLINICAL CANCER RESEARCH LA English DT Article ID MICROARRAY ANALYSIS; MOUSE-BRAIN; INJURY; MECHANISMS; IRRADIATION; INDUCTION; EXPOSURE; STRESS; DAMAGE AB Purpose: There is a growing awareness that radiation-induced normal tissue injury in late-responding organs, such as the brain, kidney, and lung, involves complex and dynamic responses between multiple cell types that not only lead to targeted cell death but also acute and chronic alterations in cell function. The specific genes involved in the acute and chronic responses of these late-responding normal tissues remain ill defined; understanding these changes is critical to understanding the mechanism of organ damage. As such, the aim of the present study was to identify candidate genes involved in the development of radiation injury in the murine kidney and brain using microarray analysis. Experimental Design: A multimodality experimental approach combined with a comprehensive expression analysis was done to determine changes in normal murine tissue gene expression at 8 and 24 hours after irradiation. Results: A comparison of the gene expression patterns in normal mouse kidney and brain was strikingly different. This observation was surprising because it has been long assumed that the changes in irradiation-induced gene expression in normal tissues are preprogrammed genetic changes that are not affected by tissue-specific origin. Conclusions: This study shows the potential of microarray analysis to identify gene expression changes in irradiated normal tissue cells and suggests how normal cells respond to the damaging effects of ionizing radiation is complex and markedly different in cells of differing origin. C1 NCI, Radiat Oncol Sci Program, Radiat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Brain Tumor Ctr, Dept Radiat Oncol, Winston Salem, NC USA. Natl Taiwan Univ, Dept Elect Engn, Biomed Engn Grp, Taipei 10764, Taiwan. RP Gius, D (reprint author), NCI, Radiat Oncol Sci Program, Radiat Oncol Branch, Ctr Canc Res,NIH, Bldg 10,B3B69, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA82722]; NIDDK NIH HHS [DK51612] NR 25 TC 22 Z9 24 U1 0 U2 3 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 JUN 15 PY 2006 VL 12 IS 12 BP 3823 EP 3830 DI 10.1158/1078-0432.CCR-05-2418 PG 8 WC Oncology SC Oncology GA 054YS UT WOS:000238415100022 PM 16778110 ER PT J AU McKenzie, FE Smith, DL O'Meara, WP Forney, JR Magill, AJ Permpanich, B Erhart, LM Sirichaisinthop, J Wongsrichanalai, C Gasser, RA AF McKenzie, F. Ellis Smith, David L. O'Meara, Wendy P. Forney, J. Russ Magill, Alan J. Permpanich, Barnyen Erhart, Laura M. Sirichaisinthop, Jeeraphat Wongsrichanalai, Chansuda Gasser, Robert A., Jr. TI Fever in patients with mixed-species malaria SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; BLOOD-STAGE DYNAMICS; PLASMODIUM-VIVAX; FALCIPARUM-MALARIA; PARASITE DENSITY; INFECTIONS; THAILAND; POPULATION; VACCINE; PUNJAB AB Background. Clinical symptoms of mixed-species malaria infections have been variously reported as both less severe and more severe than those of single-species infections. Methods. Oral temperatures were taken from and blood slides were prepared for 2308 adults who presented at outpatient malaria clinics in Tak Province (Thailand) during May-August 1998, May-July 1999, and May-June 2001 with malaria infections diagnosed by 2 expert research microscopists, each of whom was blinded to the other's reports. Results. In each year, temperatures of patients with mixed Plasmodium vivax-Plasmodium falciparum infections were higher than temperatures of patients with P. vivax or P. falciparum infections. In every mixed-species case, P. falciparum parasitemia was higher than P. vivax parasitemia, but patient temperature was not correlated with the parasitemia of either species or with the total parasitemia. Conclusions. Among adults who self-report to malaria clinics in western Thailand, patients with mixed P. vivax-P. falciparum infections have higher fevers than patients with single-species infections, a distinction that cannot be attributed to differences in parasitemia. This observation warrants more detailed investigations, spanning wider ranges of ages and transmission environments. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Minist Publ Hlth, Armed Forces Res Inst Med Sci, Bangkok, Thailand. Minist Publ Hlth, Dept Communicable Dis Control, Bangkok, Thailand. NAMRU 2, Jakarta, Indonesia. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bldg 16, Bethesda, MD 20892 USA. EM em225k@nih.gov RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU Intramural NIH HHS [Z99 TW999999] NR 40 TC 13 Z9 13 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2006 VL 42 IS 12 BP 1713 EP 1718 DI 10.1086/504330 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 043TO UT WOS:000237624800010 PM 16705577 ER PT J AU Qian, JH Dong, YJ Pang, YYS Ibrahim, R Berzofsky, JA Schiller, JT Khleif, SN AF Qian, JH Dong, YJ Pang, YYS Ibrahim, R Berzofsky, JA Schiller, JT Khleif, SN TI Combined prophylactic and therapeutic cancer vaccine: Enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA-A2 mice SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE vaccine; HPV 16; CTL; chimeric VLP; HPV 16 E2; dendritic cells ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; COTTONTAIL RABBIT PAPILLOMAVIRUS; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; CERVICAL-CANCER; GM-CSF; INTRAEPITHELIAL NEOPLASIA; PROTECTIVE IMMUNITY; TUMOR-REGRESSION AB We identified the strategies to induce a CTL response to human papillomavirus (HPV) 16 E2 in HLA-A2 transgenic mice (AAD). A chimeric HPV16 virus-like particle (VLP) that includes full length HPV16 E7 and E2 (VLP-E7E2) was generated. The combination of E2 and E7 has the advantage that E2 is expressed in early dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions. Since T cell response to E2 is less defined, we first evaluated the strategies to enhancing CD8(+) T cell responses to HPV E7, using different combinations of immune-modulators with VLP-E7E2. Data showed that the CTL response to E7 could be significantly enhanced by coinjection of GM-CSF and antiCD40 antibodies with chimeric VLP-E7E2 without adjuvant. However, using the same combination, a low level of CD8(+) T cell response to E2 was detected. To enhance the CD8(+) T cell response to E2, we analyzed T cell epitopes from E2 sequence. A heterogonous prime-boost with chimeric VLP-E7E2 and E2 peptides was performed. The data showed that the priming with chimeric VLP-E7E2, followed by boosting with E2 peptides, gave a better CTL response than 2 immunizations with E2 peptides. The enhanced immunity is due to the increase of CD11c(+) and CD11c(+) CD40(+) double positive dendritic cells in mice that received immune-modulators, GM-CSF and antiCD40. Furthermore, the level of anti-L1 antibodies remains similar in mice immunized with chimeric VLP with/without immune-modulators. Thus, the data suggested that the chimeric VLP-E7E2 has a therapeutic potential for the treatment of HPV-associated CINs and cancer without diminishing VLPs potential as a prophylactic vaccine by inducing anti-L1 antibodies against free virus. (c) 2006 Wiley-Liss, hic. C1 NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. NCI, Vaccine Branch, Natl Naval Med Ctr, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Qian, JH (reprint author), NCI, Vaccine Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM qianj@mail.nih.gov NR 48 TC 21 Z9 24 U1 0 U2 4 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 JUN 15 PY 2006 VL 118 IS 12 BP 3022 EP 3029 DI 10.1002/ijc.21781 PG 8 WC Oncology SC Oncology GA 039UA UT WOS:000237331600015 PM 16425257 ER PT J AU Zhang, XH Andreotti, G Gao, YT Deng, J Liu, EJ Rashid, A Wu, K Sun, L Sakoda, LC Cheng, JR Shen, MC Wang, BS Han, TQ Zhang, BH Gridley, G Fraumeni, JF Hsing, AW AF Zhang, XH Andreotti, G Gao, YT Deng, J Liu, EJ Rashid, A Wu, K Sun, L Sakoda, LC Cheng, JR Shen, MC Wang, BS Han, TQ Zhang, BH Gridley, G Fraumeni, JF Hsing, AW TI Tea drinking and the risk of biliary tract cancers and biliary stones: A population-based case-control study in Shanghai, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE biliary tract cancers; gallstones; tea consumption; polyphenol; epidemiology ID GREEN TEA; GALLBLADDER CANCER; CARCINOMA-CELLS; EPITHELIAL-CELLS; LUNG-CANCER; CONSUMPTION; EPIGALLOCATECHIN-3-GALLATE; EXPRESSION; BILE; POLYPHENOL AB Biliary tract cancers, encompassing tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Apart from gallstones, etiologic factors for biliary tract cancer are not clearly defined. Several epidemiologic studies have suggested that consumption of tea, especially green tea, is protective against a variety of cancers, including gastrointestinal malignancies. As part of a large population-based case-control study of biliary tract disease in Shanghai, China, we evaluated the effects of tea consumption on the risk of biliary tract cancers and biliary stones. The study included 627 incident cases with biliary tract cancer, 1,037 cases with biliary stones and 959 randomly selected controls. Study subjects were interviewed to ascertain data on demographic, medical and dietary factors, including tea consumption. Forty-one percent of the controls were ever tea drinkers, defined as those who consumed at least 1 cup of tea per day for at least 6 months. After adjustment for age, education and body mass index, among women, ever tea drinkers had significantly reduced risks of biliary stones (OR = 0.73, 95% CI = 0.54-0.98) and gallbladder cancer (OR = 0.56, 95% CI = 0.380.83). The inverse relationship between tea consumption and gallbladder cancer risk was independent of gallstone disease. Among men, tea drinkers were more likely to be cigarette smokers, and the risk estimates were generally below 1.0, but were not statistically significant. Further studies are needed to confirm these results in other populations and clarify the hormonal and other mechanisms that may be involved. (c) 2006 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China. Second Mil Univ, Dept Surg, Ruijin Hosp, Shanghai, Peoples R China. Second Mil Univ, Inst Oriental Hepatobililary Surg, Shanghai, Peoples R China. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS 7058, Rockville, MD 20852 USA. EM hsinga@mail.nih.gov RI liu, enju/B-2136-2010; liu, enju/F-4062-2010; Zhang, Xuehong/E-6219-2012 FU Intramural NIH HHS [ZIA CP010158-09] NR 44 TC 18 Z9 19 U1 1 U2 6 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 JUN 15 PY 2006 VL 118 IS 12 BP 3089 EP 3094 DI 10.1002/ijc.21748 PG 6 WC Oncology SC Oncology GA 039UA UT WOS:000237331600023 PM 16395699 ER PT J AU Landgren, O Linet, MS McMaster, ML Gridley, G Hemminki, K Goldin, LR AF Landgren, O Linet, MS McMaster, ML Gridley, G Hemminki, K Goldin, LR TI Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: A population-based case-control study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE hematopoietic malignancies; multiple myeloma; autoimmune disease; family history; familial aggregation ID LYMPHOPROLIFERATIVE TUMORS; PERNICIOUS-ANEMIA; CANCER-RISK; HISTORY; BLACKS; WHITES; MORTALITY; ETIOLOGY; LEUKEMIA; DISEASES AB A population-based case-control study was conducted to evaluate risk of developing multiple myeloma (MM) associated with personal history of autoimmune diseases and occurrence of autoimmune and selected hematologic disorders in first-degree relatives. Data were obtained for all (n = 8,406) MM cases diagnosed in Sweden (1958-1998), with linkable relatives, 16,543 matched controls and first-degree relatives of cases (n = 22,490) and controls (it = 44,436). Odds ratios (ORs) were calculated to quantify the risk of MM in relation to personal/family history of 32 autoimmune disorders. Familial aggregation of malignancies was evaluated in a marginal survival model using relatives as the cohort. The risk for MM was significantly elevated among subjects with a personal history of pernicious anemia (OR = 3.27; 2.22-4.83) and individuals with a family history of systemic lupus erythematosus (OR = 2.66; 1.12-6.32). Compared with controls, relative risk (RR) of MM was significantly increased (RR = 1.67; 1.02-2.73) in relatives of cases, particularly relatives of probands aged >= 65 at diagnosis (RR = 2.50; 1.19-5.27). Risks were nearly 4-fold elevated among female relatives (RR = 3.97; 1.54-10.2) and among relatives of female probands (RR = 3.74; 1.58-8.83). MM cases had more cases of monoclonal gammopathy of undetermined significance (MGUS) among their relatives than controls, but the numbers were too small to be conclusive. There was generally no increase in risk of MM in probands whose relatives had hematologic malignancies other than MM. These findings do not support a strong association between personal/familial autoimmune diseases and MM. However, MM itself shows significant familial aggregation, implicating the etiologic importance of this type of hematological neoplasm and perhaps MGUS in germ line genes. (c) 2006 Wiley-Liss, Inc. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Inst, Dept Biosci, Novum, Stockholm, Sweden. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Bldg EPS Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov FU Intramural NIH HHS NR 30 TC 85 Z9 88 U1 1 U2 3 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 JUN 15 PY 2006 VL 118 IS 12 BP 3095 EP 3098 DI 10.1002/ijc.21745 PG 4 WC Oncology SC Oncology GA 039UA UT WOS:000237331600024 PM 16395700 ER PT J AU Rusiecki, JA Hou, LF Lee, WJ Blair, A Dosemeci, M Lubin, JH Bonner, M Samanic, C Hoppin, JA Sandler, DP Alavanja, MCR AF Rusiecki, JA Hou, LF Lee, WJ Blair, A Dosemeci, M Lubin, JH Bonner, M Samanic, C Hoppin, JA Sandler, DP Alavanja, MCR TI Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE metolachlor; cancer; pesticides; herbicides; applicators ID HERBICIDES; ALACHLOR; FARMERS; SAMPLE; COHORT; CELLS; RISK; RAT AB Metolachlor is one of the most widely used herbicides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to metolachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 50,193 pesticide applicators were included. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997; average length of follow-up was 7.33 years. Two metolachlor exposure metrics were used : (i) lifetime days personally mixed or applied metolachlor and (H) intensity-weighted lifetime days (lifetime days X an intensity level). Poisson regression analysis was used to estimate relative risks (RR) and 95% confidence intervals (95%CI) for cancer subtypes by tertiles of metolachlor exposure. No clear risk for any cancer subtype was found for exposure to metolachlor. A significantly decreased RR was found for prostate cancer in the highest category of lifetime days exposure (RR = 0.59; 95% CI, 0.39-0.89) and in the second highest category of intensity-weighted lifetime days exposure (RR = 0.66; 95%CI, 0.45-0.97); however, the test for trend was not significant for either exposure metric. A nonsignificantly increased risk was found for lung cancer with lifetime days exposure in the highest category (RR = 2.37; 95%CI, 0.97-5.82, p-trend = 0.03) but not with intensity-weighted lifetime days. Given the widespread use of metolachlor and the frequent detection of metolachlor in both surface and ground water, future analyses of the AHS will allow further examination of long-term health effects, including lung cancer and the less common cancers. (c) 2006 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Rusiecki, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd,PMB Room A1039, Bethesda, MD 20814 USA. EM jrusiecki@usuhs.mil OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 31 TC 31 Z9 35 U1 0 U2 7 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 JUN 15 PY 2006 VL 118 IS 12 BP 3118 EP 3123 DI 10.1002/ijc.21758 PG 6 WC Oncology SC Oncology GA 039UA UT WOS:000237331600027 PM 16425265 ER PT J AU Cross, AJ Gunter, MJ Wood, RJ Pietinen, P Taylor, PR Virtamo, J Albanes, D Sinha, R AF Cross, AJ Gunter, MJ Wood, RJ Pietinen, P Taylor, PR Virtamo, J Albanes, D Sinha, R TI Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE red meat; iron; colorectal cancer ID DIETARY IRON; COLON-CANCER; WHOLE DIET; CELL-PROLIFERATION; MEAL COMPOSITION; RECTAL-CANCER; DNA-DAMAGE; ABSORPTION; STORES; COHORT AB In vitro and in vivo studies have associated iron with both the initiation and promotional stages of carcinogenesis. We investigated whether iron was associated with colorectal cancer in a nested case-control study within the alpha-tocopherol, beta-carotene cancer prevention study cohort. Exposure was assessed at baseline, using a 276-item food frequency questionnaire and a fasting serum sample. The study included 130 colorectal cancer cases (73 colon cancers and 57 rectal cancers) and 260 controls. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Supplemental iron intake was only reported for 4 cases and 18 controls; therefore, we were unable to obtain meaningful results for this variable. Comparing the highest to the lowest quartiles, there was an inverse association between serum ferritin and colorectal cancer risk (OR = 0.4, 95% CI = 0.2-0.9) and a suggestion of an inverse association between dietary iron and colorectal cancer risk (OR = 0.4, 95% CI = 0.1-1.1). In addition, serum ferritin, serum iron and transferrin saturation were all inversely associated with colon cancer risk specifically (OR = 0.2, 95% CI = 0.14.7, p trend = 0.02; OR = 0.2, 95% 61 0.1-0.9, p trend = 0.05; OR = 0.1, 95% CI = 0.02-0.5, p trend 0.003, respectively), whereas serum unsaturated iron binding capacity was positively associated with colon cancer risk (OR = 4.7, 95% CI = 1.4-15.1, p trend = 0.009). In summary, we found a significant inverse association between several serum iron indices and colon cancer risk. (c) 2006 Wiley-Liss, Inc. C1 NCI, Natl Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. Tufts Univ, Mineral Bioavailabil Lab, Boston, MA 02111 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Gent, NIH,DHHS, Rockville, MD USA. RP Cross, AJ (reprint author), 6120 Execut Blvd, Rockville, MD USA. EM crossa@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 42 TC 28 Z9 28 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 JUN 15 PY 2006 VL 118 IS 12 BP 3147 EP 3152 DI 10.1002/ijc.21780 PG 6 WC Oncology SC Oncology GA 039UA UT WOS:000237331600031 PM 16425287 ER PT J AU Terry, PD Umbach, DM Taylor, JA AF Terry, PD Umbach, DM Taylor, JA TI APE1 genotype and risk of bladder cancer: Evidence for effect modification by smoking SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder neoplasms; apurinic endonuclease; polymorphism; smoking; case-control studies ID BASE EXCISION-REPAIR; HUMAN APURINIC ENDONUCLEASE; DNA-REPAIR; LUNG-CANCER; APURINIC/APYRIMIDINIC ENDONUCLEASE; FUNCTIONAL-CHARACTERIZATION; GENETIC SUSCEPTIBILITY; POLYMORPHISMS; XRCC1; VARIANTS AB Apurinic/apyrimidinic (AP) sites are common mutagenic and cytotoxic DNA lesions that arise from the loss of normal bases. APEI, the major AP endonuclease of human cells, plays a central role in the repair of AP sites through both its endonuclease and phosphodiesterase activities. A common APE1 polymorphism, a T -> G transversion (Asp 148 Glu), was previously shown to be associated with risk of lung cancer, an association that was modified by cigarette smoking. To explore the association between APE1 genotype, smoking and bladder cancer risk, we examined data from an existing case-control study of bladder cancer patients (n = 239) and control individuals (n = 215) recruited from urology clinics at 2 hospitals in North Carolina. Genotype at the polymorphic site was determined using allele-specific primer extension reactions, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. We found no overall association between APE1 genotype and bladder cancer risk. In stratified analyses, however, a positive association with risk was observed with an increasing number of Glu alleles among never smokers, but not among smokers (p-value for interaction = 0.005). We can speculate that small allelic differences that are apparent in never smokers are obscured by the large amount of DNA damage found in smokers. Given the lack of established biological mechanisms, and suboptimal numbers of subjects in some exposure categories, our findings should be interpreted cautiously. Published 2006 Wiley-Liss, Inc. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Mol Carcinogenesis, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS NR 28 TC 25 Z9 26 U1 0 U2 0 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 JUN 15 PY 2006 VL 118 IS 12 BP 3170 EP 3173 DI 10.1002/ijc.21768 PG 4 WC Oncology SC Oncology GA 039UA UT WOS:000237331600035 PM 16425270 ER PT J AU Lee, WJ Purdue, MP Stewart, P Schenk, M De Roos, AJ Cerhan, JR Severson, RK Cozen, W Hartge, P Blair, A AF Lee, WJ Purdue, MP Stewart, P Schenk, M De Roos, AJ Cerhan, JR Severson, RK Cozen, W Hartge, P Blair, A TI Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin's lymphoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE asthma; non-Hodgkin's lymphoma; pesticide exposure ID GLUCOCORTICOID THERAPY; CANCER; ALLERGY; HEALTH AB We previously reported that, although asthma did not increase the risk of non-Hodgkin's lymphoma (NHL), the risk from pesticide exposures was higher among asthmatics than that among nonasthmatics. To further evaluate this finding, we analyzed data from a population-based case-control study of NHL conducted in Iowa, Detroit, Los Angeles and Seattle. Cases (n = 668) diagnosed with NHL from 1998 to 2000 and controls (n = 543) randomly selected from the same geographical areas as that of the cases were included in this analysis. Odds ratios (OR) for the risk of NHL from potential occupational exposure to pesticides tended to be higher among asthmatics (OR = 1.7; 95% CI 0.3-9.1) when compared with that among nonasthmatics (OR = 0.9; 95% CI 0.61.5). The risks of NHL associated with pesticide exposure were also higher among asthmatics who had history of hospitalization (OR = 2.1; 95% CI 0.2-29.0) or daily medication for asthma (OR = infinite) than those among asthmatics who did not have such histories. Our results support the previous finding that the risk of NHL from pesticide exposure may be greater among asthmatics. (c) 2006 Wiley-Liss, Inc. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Univ So Calif, Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. RP Blair, A (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execeut Blvd,EPS 8118, Rockville, MD 20852 USA. EM blaira@mail.nih.gov RI Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010120-10] NR 19 TC 2 Z9 2 U1 1 U2 3 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 JUN 15 PY 2006 VL 118 IS 12 BP 3174 EP 3176 DI 10.1002/ijc.21755 PG 3 WC Oncology SC Oncology GA 039UA UT WOS:000237331600036 PM 16395708 ER PT J AU Shaw, MH Freeman, GJ Scott, MF Fox, BA Bzik, DJ Belkaid, Y Yap, GS AF Shaw, MH Freeman, GJ Scott, MF Fox, BA Bzik, DJ Belkaid, Y Yap, GS TI Tyk2 negatively regulates adaptive Th1 immunity by mediating IL-10 signaling and promoting IFN-gamma-dependent IL-10 reactivation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; TOXOPLASMA-GONDII; TYK2-DEFICIENT MICE; INTERFERON-GAMMA; LEISHMANIA-MAJOR; B10.Q/J MICE; ACTIVATED MACROPHAGES; HERITABLE DEFECT; ABSENCE; INTERLEUKIN-10 AB The Jak, Tyk2, is activated in response to IL-12 and IFN-alpha beta and promotes IFN-gamma production by Th1-type CD4 cells. Mice deficient in Tyk2 function have been previously shown to be resistant to autoimmune arthritis and septic shock but are acutely susceptible to opportunistic pathogens such as Toxoplasma gondii. In this study, we show that Tyk2, in addition to mediating the biological effects of IL-12 and IFN-alpha beta, is an important regulator for the signaling and expression of the immunosuppressive cytokine IL-10. In the absence of Tyk2, Ag-reactive CD4 cells exhibit impaired IL-10 synthesis following rechallenge of T. gondii vaccine-primed mice. The impaired IL-10 reactivation leads to unopposed antimicrobial effector mechanisms which results in a paradoxically superior protection of immune Tyk2(-/-) mice against virulent T. gondii challenge. We further demonstrate that Tyk2 indirectly controls CD4 IL-10 reactivation by signaling for maximal IFN-gamma secretion. The unexpected role of IFN-gamma in mediating IL-10 reactivation by Th1 cells provides compelling evidence that conditions driving Th1 responses establish a negative feedback loop, which will ultimately lead to its autoregulation. Thus, Tyk2 can be viewed as a dual-function Jak, mediating both pro and anti-inflammatory cytokine responses. C1 Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Hanover, NH 03756 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yap, GS (reprint author), Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Box GB-6, Providence, RI 02912 USA. EM George_Yap@Brown.edu FU NCI NIH HHS [CA84500]; NIAID NIH HHS [R01 AI050618, AI 50618, AI39671, R01 AI041930, R01 AI041930-07, R21 AI052026] NR 35 TC 61 Z9 66 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2006 VL 176 IS 12 BP 7263 EP 7271 PG 9 WC Immunology SC Immunology GA 050QA UT WOS:000238101800015 PM 16751369 ER PT J AU Hager-Braun, C Katinger, H Tomer, KB AF Hager-Braun, Christine Katinger, Hermann Tomer, Kenneth B. TI The HIV-neutralizing monoclonal antibody 4E10 recognizes N-terminal sequences on the native antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP41 TRANSMEMBRANE GLYCOPROTEIN; TRANSFORM INFRARED-SPECTROSCOPY; GP120 ENVELOPE GLYCOPROTEIN; MEDIATED MEMBRANE-FUSION; PROXIMAL EXTERNAL REGION; TRYPTOPHAN-RICH REGION; MASS-SPECTROMETRY; CELL-FUSION; PEPTIDE AB Characterization of the epitope recognized by the broadly neutralizing anti-HIV Ab 4E10 has, heretofore, focused on a linear sequence from the gp4l pretransmembrane region (PTMR). Attempts to generate neutralizing Abs based on this linear epitope sequence have been unsuccessful. We have characterized the antigenic determinants on recombinant glycosylated full-length Ags, and nonglycosylated and truncated Ags recognized by 4E10 using epitope extraction and excision assays in conjunction with MALDI mass spectrometry. The mAb recognized the peptides (34)LWVTVYYGVPVWK(46) and (512)AVGIGAVFLGFLGAAGST MGAASMTLTVQAR(542) located at the N-terminal region of gp120 and gp4l, respectively. Immunoassays verified AV(L/M)FL GFLGAA as the gp4l epitope core. Recognition of the peptide from the gp4l PTMR was detected only in constructs in which the N termini of the mature envelope proteins were missing. In this region, the epitope core is located in the sequence (672)WFDIT NWLWY(681). We hypothesize that the hydrophobic surface of the paratope functions as a "trap" for the viral sequences, which are responsible for insertion into the host cell membrane. As the N-terminal region of gp120, the fusogenic peptide of gp41, and the PTMR of gp4l show high sequence homology among various HIV strains, this model is consistent with the, broadly neutralizing capabilities of 4E10. C1 Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Univ Nat Resources & Appl Life Sci, Inst Appl Microbiol, Vienna, Austria. RP Hager-Braun, C (reprint author), Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM christine_hager-braun@ncsu.edu RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 49 TC 28 Z9 28 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2006 VL 176 IS 12 BP 7471 EP 7481 PG 11 WC Immunology SC Immunology GA 050QA UT WOS:000238101800039 PM 16751393 ER PT J AU Huang, JP Kerstann, KW Ahmadzadeh, M Li, YF El-Gamil, M Rosenberg, SA Robbins, PF AF Huang, JP Kerstann, KW Ahmadzadeh, M Li, YF El-Gamil, M Rosenberg, SA Robbins, PF TI Modulation by IL-2 of CD70 and CD27 expression on CD8(+) T cells: Importance for the therapeutic effectiveness of cell transfer immunotherapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; RECOMBINANT INTERLEUKIN-2; METASTATIC MELANOMA; CANCER REGRESSION; TUMOR; RESPONSES; LIGAND; ACTIVATION; RECEPTOR; SURVIVAL AB Proper T cell function relies on the integration of signals delivered by Ag, cytokine, and costimulatory receptors. In this study, the interactions between IL-2, CD27, and its ligand CD70 and their effects on human T cell function were examined. Unstimulated CD8(+) T cells expressed relatively low levels of CD70 and high levels of CD27. Incubation in vitro with high doses of IL-2 (3,000 IU/ml) or administration of IL-2 in vivo resulted in substantial up-regulation of CD70 expression and the concomitant loss of cell surface CD27 expression on CD8(+) cells. Withdrawal of IL-2 from activated CD8(+) T cells that had been maintained in IL-2 resulted in a reversal of the expression of these two markers, whereas reciprocal changes were seen following treatment of PBMCs with IL-2. The proliferation observed in cells stimulated with IL-2 primarily occurred in a subset of the CD70(+)CD8(+) T cells that up-regulated IL-2 receptor expression but did not occur in CD70(-)CD8(+) T cells. Blocking CD70 resulted in a significant reduction of T cell proliferation induced by high-dose IL-2, indicating that the interaction of CD70 with CD27 played a direct role in T cell activation mediated by IL-2. Finally, studies conducted on tumor-infiltrating lymphocyte (TIL) samples that were administered to melanoma patients indicated that the size of the pool of CD27(+)CD8(+) T cells in bulk TILs was highly associated (p = 0.004) with the ability of these TELs to mediate tumor regression following adoptive transfer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. EM paul_robbins@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 41 TC 91 Z9 94 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2006 VL 176 IS 12 BP 7726 EP 7735 PG 10 WC Immunology SC Immunology GA 050QA UT WOS:000238101800066 PM 16751420 ER PT J AU Geisbert, TW Hensley, LE Kagan, E Yu, EYZ Geisbert, JB Daddario-DiCaprio, K Fritz, EA Jahrling, PB McClintock, K Phelps, JR Lee, ACH Judge, A Jeffs, LB MacLachlan, I AF Geisbert, TW Hensley, LE Kagan, E Yu, EYZ Geisbert, JB Daddario-DiCaprio, K Fritz, EA Jahrling, PB McClintock, K Phelps, JR Lee, ACH Judge, A Jeffs, LB MacLachlan, I TI Postexposure protection of guinea pigs against a lethal Ebola virus challenge is conferred by RNA interference SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 13th International Congress of Virology CY JUL 23-28, 2005 CL San Francisco, CA ID VIVO GENE-EXPRESSION; MARBURG-VIRUS; IN-VIVO; HEMORRHAGIC-FEVER; NONHUMAN-PRIMATES; DENDRITIC CELLS; MODIFIED SIRNAS; INFECTED MICE; PLASMID DNA; MOUSE MODEL AB Background. Ebola virus (EBOV) infection causes a frequently fatal hemorrhagic fever (HF) that is refractory to treatment with currently available antiviral therapeutics. RNA interference represents a powerful, naturally occurring biological strategy for the inhibition of gene expression and has demonstrated utility in the inhibition of viral replication. Here, we describe the development of a potential therapy for EBOV infection that is based on small interfering RNAs (siRNAs). Methods. Four siRNAs targeting the polymerase (L) gene of the Zaire species of EBOV (ZEBOV) were either complexed with polyethylenimine (PEI) or formulated in stable nucleic acid-lipid particles (SNALPs). Guinea pigs were treated with these siRNAs either before or after lethal ZEBOV challenge. Results. Treatment of guinea pigs with a pool of the L gene-specific siRNAs delivered by PEI polyplexes reduced plasma viremia levels and partially protected the animals from death when administered shortly before the ZEBOV challenge. Evaluation of the same pool of siRNAs delivered using SNALPs proved that this system was more efficacious, as it completely protected guinea pigs against viremia and death when administered shortly after the ZEBOV challenge. Additional experiments showed that 1 of the 4 siRNAs alone could completely protect guinea pigs from a lethal ZEBOV challenge. Conclusions. Further development of this technology has the potential to yield effective treatments for EBOV HF as well as for diseases caused by other agents that are considered to be biological threats. C1 USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Protiva Biotherapeut, Burnaby, BC, Canada. NIAID, Bethesda, MD 20892 USA. RP Geisbert, TW (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD 21702 USA. EM tom.geisbert@amedd.army.mil NR 43 TC 169 Z9 177 U1 1 U2 27 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 JUN 15 PY 2006 VL 193 IS 12 BP 1650 EP 1657 DI 10.1086/504267 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 042TV UT WOS:000237553400007 PM 16703508 ER PT J AU Ding, K Lu, YP Nikolovska-Coleska, Z Wang, GP Qiu, S Shangary, S Gao, W Qin, DG Stuckey, J Krajewski, K Roller, PP Wang, SM AF Ding, Ke Lu, Yipin Nikolovska-Coleska, Zaneta Wang, Guoping Qiu, Su Shangary, Sanjeev Gao, Wei Qin, Dongguang Stuckey, Jeanne Krajewski, Krzysztof Roller, Peter P. Wang, Shaomeng TI Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID P53; ANTAGONISTS; ACTIVATION; CANCER; CELLS; DISCOVERY; BINDING; DOMAIN; MDM-2 AB Potent, specific, non-peptide small-molecule inhibitors of the MDM2-p53 interaction were successfully designed. The most potent inhibitor ( MI-63) has a K-i value of 3 nM binding to MDM2 and greater than 10 000-fold selectivity over Bcl-2/Bcl-xL proteins. MI-63 is highly effective in activation of p53 function and in inhibition of cell growth in cancer cells with wild-type p53 status. MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells. C1 Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Life Sci Inst, Ann Arbor, MI 48109 USA. NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. RP Wang, SM (reprint author), Univ Michigan, Ctr Comprehens Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM shaomeng@umich.edu RI Wang, Shaomeng/E-9686-2010; Ding, Ke/B-3257-2010; OI ding, ke/0000-0001-8167-0476; Ding, Ke/0000-0001-9016-812X FU NCI NIH HHS [P30CA046592, P50CA069568, P50CA097248, R01CA121279] NR 19 TC 411 Z9 424 U1 7 U2 66 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 15 PY 2006 VL 49 IS 12 BP 3432 EP 3435 DI 10.1021/jm051122a PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 050UR UT WOS:000238114700001 PM 16759082 ER PT J AU Vazquez, ME Blanco, JB Salvadori, S Trapella, C Argazzi, R Bryant, SD Jinsmaa, Y Lazarus, LH Negri, L Giannini, E Lattanzi, R Colucci, M Balboni, G AF Vazquez, M. Eugenio Blanco, Juan B. Salvadori, Severo Trapella, Claudio Argazzi, Roberto Bryant, Sharon D. Jinsmaa, Yunden Lazarus, Lawrence H. Negri, Lucia Giannini, Elisa Lattanzi, Roberta Colucci, Mariantonella Balboni, Gianfranco TI 6-N,N-dimethylamino-2,3-naphthalimide: A new environment-sensitive fluorescent probe in delta- and mu-selective opioid peptides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DMT-TIC PHARMACOPHORE; LIVING CELLS; AMINO-ACID; OPIATE RECEPTOR; HIGH-AFFINITY; POTENT; ANALOGS; ANTAGONISM; AGONISTS; BINDING AB new environment-sensitive fluorophore, 6-N,N-(dimethylamino)-2,3-naphthalimide (6DMN) was introduced in the delta-selective opioid peptide agonist H-Dmt-Tic-Glu-NH2 and in the mu-selective opioid peptide agonist endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2). Environment-sensitive fluorophores are a special class of chromophores that generally exhibit a low quantum yield in aqueous solution but become highly fluorescent in nonpolar solvents or when bound to hydrophobic sites in proteins or membranes. New fluorescent delta-selective irreversible antagonists (H-Dmt-Tic-Glu-NH-(CH2)(5)-CO-Dap(6DMN)-NH2 (1) and H-Dmt-Tic-Glu-Dap(6DMN)-NH2 ( 2)) were identified as potential fluorescent probes showing good properties for use in studies of distribution and internalization of delta receptors by confocal laser scanning microscopy. C1 Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. Univ Santiago de Compostela, CSIC, Dept Quim Organ, Santiago De Compostela 15782, Spain. Univ Santiago de Compostela, CSIC, Unidad Asociada, Santiago De Compostela 15782, Spain. Univ Ferrara, Dept Chem, I-44100 Ferrara, Italy. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy. Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy. RP Balboni, G (reprint author), Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. EM gbalboni@unica.it RI Vazquez, M. Eugenio/D-4083-2012; Trapella, Claudio/I-2128-2012; Argazzi, Roberto/C-4819-2015; OI Vazquez, M. Eugenio/0000-0001-7500-985X; Trapella, Claudio/0000-0002-6666-143X; Argazzi, Roberto/0000-0002-2619-6860; LATTANZI, Roberta/0000-0002-6377-9256 FU Intramural NIH HHS [Z01 ES090053-18] NR 42 TC 37 Z9 37 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 15 PY 2006 VL 49 IS 12 BP 3653 EP 3658 DI 10.1021/jm060343t PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 050UR UT WOS:000238114700026 PM 16759107 ER PT J AU Babin, V Baucom, J Darden, TA Sagui, C AF Babin, Volodymyr Baucom, Jason Darden, Thomas A. Sagui, Celeste TI Molecular dynamics simulations of DNA with polarizable force fields: Convergence of an ideal B-DNA structure to the crystallographic structure SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PARTICLE-MESH-EWALD; T-G-G; NUCLEIC-ACIDS; D(CCAACGTTGG)(2) DECAMER; BIOMOLECULAR SIMULATIONS; CRYSTAL ENVIRONMENT; AB-INITIO; C-G; MECHANICS; WATER AB We have investigated to what extent molecular dynamics (MD) simulations can reproduce DNA sequence-specific features, given different electrostatic descriptions and different cell environments. For this purpose, we have carried out multiple unrestrained MD simulations of the DNA duplex d(CCAACGTTGG)(2). With respect to the electrostatic descriptions, two different force fields are studied: a traditional description based on atomic point charges and a polarizable force field. With respect to the cell environment, the difference between crystal and solution environments is emphasized, as well as the structural importance of divalent ions. By imposing the correct experimental unit cell environment, an initial configuration with two ideal B-DNA duplexes in the unit cell is shown to converge to the crystallographic structure. This convergence is measured by the appearance of sequence-dependent features that very closely resemble the crystallographic ones as well as by the decay of the all-atom root-mean-squared coordinates deviations (RMSD) with respect to the crystallographic structure. Given the appropriate crystallographic constraints, this is the first example of multiple nanosecond molecular dynamics trajectory that shows an ideal B-DNA model converging to an experimental structure, with a significant decay of RMSD. C1 N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Sagui, C (reprint author), N Carolina State Univ, Dept Phys, Raleigh, NC 27695 USA. EM sagui@ncsu.edu NR 52 TC 43 Z9 43 U1 1 U2 12 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 JUN 15 PY 2006 VL 110 IS 23 BP 11571 EP 11581 DI 10.1021/jp061421r PG 11 WC Chemistry, Physical SC Chemistry GA 050QK UT WOS:000238102800078 PM 16771434 ER PT J AU Zhu, P Liu, J Bess, J Chertova, E Lifson, JD Grise, H Ofek, GA Taylor, KA Roux, KH AF Zhu, P Liu, J Bess, J Chertova, E Lifson, JD Grise, H Ofek, GA Taylor, KA Roux, KH TI Distribution and three-dimensional structure of AIDS virus envelope spikes SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ELECTRON TOMOGRAPHY; HIV-1 GP41; NEUTRALIZING ANTIBODIES; GLYCOPROTEIN TRIMERS; ATOMIC-STRUCTURE; TYPE-1 MATRIX; GP120 CORE; FUSION; INFECTIVITY AB Envelope glycoprotein (Env) spikes on AIDS retroviruses initiate infection of host cells and are therefore targets for vaccine development. Though crystal structures for partial Env subunits are known, the structure and distribution of native Env spikes on virions is obscure. We applied cryoelectron microscopy tomography to define ultrastructural details of spikes. Virions of wild-type human immunodeficiency virus 1 (HIV-1) and a mutant simian immunodeficiency virus (SIV) had similar to 14 and similar to 73 spikes per particle, respectively, with some clustering of HIV-1 spikes. Three-dimensional averaging showed that the surface glycoprotein (gp120) 'head' of each subunit of the trimeric SIV spike contains a primary mass, with two secondary lobes. The transmembrane glycoprotein 'stalk' of each trimer is composed of three independent legs that project obliquely from the trimer head, tripod-like. Reconciling available atomic structures with the three-dimensional whole spike density map yields insights into the orientation of Env spike structural elements and possible structural bases of their functions. C1 Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roux, KH (reprint author), Florida State Univ, Dept Biol Sci, B-157, Tallahassee, FL 32306 USA. EM roux@bio.fsu.edu RI Ofek, Gilad/A-6965-2010; Bess, Jr., Julian/B-5343-2012 FU NIAID NIH HHS [R01 AI055461]; NIGMS NIH HHS [R01 GM030598] NR 48 TC 414 Z9 425 U1 8 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 15 PY 2006 VL 441 IS 7095 BP 847 EP 852 DI 10.1038/nature04817 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 052SL UT WOS:000238254100036 PM 16728975 ER PT J AU Wiedemann, HP Wheeler, AP Bernard, GR Thompson, BT Hayden, D deBoisblanc, B Connors, AF Hite, RD Harabin, AL AF Wiedemann, HP Wheeler, AP Bernard, GR Thompson, BT Hayden, D deBoisblanc, B Connors, AF Hite, RD Harabin, AL CA Natl Heart Lung Blood Inst Acute TI Comparison of two fluid-management strategies in acute lung injury SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY ILL PATIENTS; PRESSURE PULMONARY-EDEMA; GOAL-DIRECTED THERAPY; OXYGEN DELIVERY; SEPTIC SHOCK; SUPRANORMAL VALUES; PROSPECTIVE TRIAL; PATIENT SAFETY; FUROSEMIDE AB BACKGROUND: Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion. METHODS In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology. RESULTS: The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent). The mean (+/-SE) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen] x 100) and the lung injury score and increased the number of ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06). CONCLUSIONS: Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. C1 Cleveland Clin, Dept Pulm Allergy & Crit Care Med, Cleveland, OH 44195 USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27109 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Wiedemann, HP (reprint author), Cleveland Clin, Dept Pulm Allergy & Crit Care Med, 9500 Euclid Ave,Desk A-90, Cleveland, OH 44195 USA. EM wiedemh@ccf.org OI Wiedemann, Herbert/0000-0002-4587-4401 NR 37 TC 1275 Z9 1353 U1 7 U2 43 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 JUN 15 PY 2006 VL 354 IS 24 BP 2564 EP 2575 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 052KU UT WOS:000238233400006 ER PT J AU Xiang, XH Wang, HL Wu, WR Guo, Y Cao, DY Wang, HS Zhao, Y AF Xiang, XH Wang, HL Wu, WR Guo, Y Cao, DY Wang, HS Zhao, Y TI Ethological analysis of scopolamine treatment or pretreatment in morphine dependent rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE morphine dependence; morphine withdrawal signs; scopolamine; morphine excretion ID VENTRAL TEGMENTAL AREA; NALOXONE-PRECIPITATED WITHDRAWAL; NUCLEUS-ACCUMBENS; LOCUS-COERULEUS; MUSCARINIC RECEPTORS; BRAIN ACETYLCHOLINE; COCAINE ADDICTION; DOPAMINE RELEASE; NITRIC-OXIDE; EXPRESSION AB Although scopolamine is currently used to treat morphine addiction in humans, its extensive actions on behaviors have not been systematically analyzed yet, and the underlying mechanisms of its effects still remain ambiguous. The present study was carried out to clarify the possible mechanisms by evaluating the effects of scopolamine pretreatment and treatment on naloxone-precipitated withdrawal signs and some of other general behaviors in morphine dependent rats. Our results showed that scopolamine pretreatment and treatment attenuated naloxone-precipitated withdrawal signs including jumping, writhing posture, weight loss, genital grooming, teeth-chattering, ptosis, diarrhea and irritability, except for wet dog shakes, while general behaviors such as water intake, urine volume and morphine excretion in urine were increased. Our findings suggest that scopolamine has significant actions in the treatment of opiate addiction, which might result from increasing morphine excretion from urine. (c) 2006 Elsevier Inc. All rights reserved. C1 Xian Jiaotong Univ, Key Lab Environm & Genes Related Dis, Minist Educ, Xian 710061, Shaanxi, Peoples R China. Xian Jiaotong Univ, Dept Physiol & Pathophysiol, Sch Med, Xian 710061, Shaanxi, Peoples R China. NIDA, Cellular Neurobiol Res Branch, IRP, NIH, Baltimore, MD 21224 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. RP Zhao, Y (reprint author), Xian Jiaotong Univ, Key Lab Environm & Genes Related Dis, Minist Educ, Xian 710061, Shaanxi, Peoples R China. EM xiaohuixiang@163.com; zhaoy502@mail.xjtu.edu.cn OI xiang, xiaohui/0000-0002-5762-5007 NR 65 TC 9 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JUN 15 PY 2006 VL 88 IS 1-2 BP 183 EP 190 DI 10.1016/j.physbeh.2006.03.029 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 057MC UT WOS:000238598900024 PM 16690091 ER PT J AU Ishii, Y Thomas, AO Guo, XE Hung, CT Chen, FH AF Ishii, Y Thomas, AO Guo, XE Hung, CT Chen, FH TI Localization and distribution of cartilage oligomeric matrix protein in the rat intervertebral disc SO SPINE LA English DT Article DE cartilage oligomeric matrix protein; intervertebral disc; extracellular matrix ID MULTIPLE EPIPHYSEAL DYSPLASIA; IN-VIVO; TAIL MODEL; EXTRACELLULAR-MATRIX; ARTICULAR-CARTILAGE; CYCLIC COMPRESSION; LUMBAR DISC; COMP; EXPRESSION; PSEUDOACHONDROPLASIA AB Study Design. Whole rat intervertebral disc (IVD), as well as the anulus fibrosus (AF) and the nucleus pulposus (NP) were studied using immunoblot, immunohistochemistry, and reverse-transcription followed by polymerase chain reaction (RT-PCR) methods to investigate the expression and distribution of cartilage oligomeric matrix protein (COMP). Objectives. To investigate the expression and distribution patterns of COMP in normal IVD. Summary of Background Data. COMP is an extracellular matrix protein abundantly expressed in articular and growth plate cartilage, as well as bone, ligament, tendon, and synovium. The potential importance of COMP to the spine has been underscored by its mutations that lead to skeletal dysplasia with characteristic platyspondyly. However, the expression and distribution of COMP in spine and IVD has not been illustrated before. Methods. The presence of COMP protein was investigated by immunoblotting using a COMP antibody F8 on protein extractions from whole IVD and AF or NP. To compare the expression levels of COMP between lumbar and tail IVDs, and between AF and NP of the IVD, wet weight of the tissues were used for normalization. To show that COMP can be made by IVD cells in situ, RT-PCR was used to investigate the COMP mRNA message. The distribution patterns of COMP in IVD were investigated using immunohistochemistry studies with COMP antibody F8. Results. COMP is expressed at both the protein and mRNA levels in both the AF and NP of both the lumbar spine and tail IVD. Immunohistochemistry studies show that COMP is found in the extracellular matrix of the IVD, exhibiting lamellar distribution pattern in the AF region. When normalized to wet weight, COMP is found to be expressed at higher levels in the lumbar than the tail IVD, and within the IVD, greater in the AF than the NP region. Conclusions. Our results demonstrate the expression of COMP in both the AF and NP of the IVD. COMP is a component of the extracellular matrix of AF and NP, with a lamellar distribution pattern in the AF. Our data suggest that COMP may play a role in the normal structure of IVD. C1 Columbia Univ, Dept Orthopaed Surg, New York, NY USA. Columbia Univ, Dept Biomed Engn, New York, NY USA. RP Chen, FH (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Rm 1318,50 S Dr, Bethesda, MD 20892 USA. EM chenf1@mail.nih.gov FU NIAMS NIH HHS [AR49922] NR 63 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JUN 15 PY 2006 VL 31 IS 14 BP 1539 EP 1546 DI 10.1097/01.brs.0000221994.61882.4a PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 053RV UT WOS:000238323700005 PM 16778685 ER PT J AU Liu, J Xie, YX Merrick, BA Shen, J Ducharme, DMK Collins, J Diwan, BA Logsdon, D Waalkes, MP AF Liu, J Xie, YX Merrick, BA Shen, J Ducharme, DMK Collins, J Diwan, BA Logsdon, D Waalkes, MP TI Transplacental arsenic plus postnatal 12-O-teradecanoyl phorbol-13-acetate exposures associated with hepatocarcinogenesis induce similar aberrant gene expression patterns in male and female mouse liver SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; 12-O-teradecanoyl phorbol-13-acetate; transplacental carcinogenesis; gene expression; microarray ID HEPATOCELLULAR-CARCINOMA; DRINKING-WATER; DIMETHYLARSINIC ACID; ADULT MICE; IN-UTERO; TUMORS; CARCINOGENESIS; CANCER; PHORBOL; RISK AB Our prior work shows that in utero arsenic exposure alone is a complete transplacental carcinogen, producing hepatocellular carcinoma in adult male offspring but not in females. In a follow-up study to potentially promote arsenic-initiated tumors, mice were exposed to arsenic (85 ppm) from gestation day 8 to 18 and then exposed to 12-O-teradecanoyl phorbol-13-acetate (TPA), a well-known tumor promoter after weaning. The dermal application of TPA (2 mu g/0.1 ml acetone, twice/week for 21 weeks) after transplacental arsenic did not further increase arsenic-induced liver tumor formation in adult males but significantly increased liver tumor formation in adult females. Thus, for comparison, liver tumors and normal liver samples taken from adult male and female mice at necropsy were analyzed for aberrant gene/protein expression by microarray, real-time RT-PCR and Western blot analysis. Arsenic/TPA treatment resulted in increased expression of alpha-fetoprotein, k-ras, c-myc, estrogen receptor-alpha., cyclin D 1, cdk2na, plasminogen activator inhibitor-1, cytokeratin-8, cytokeratin-18, glutathione S-transferases and insulin-like growth factor binding proteins in liver and liver tumors from both male and female mice. Arsenic/TPA also decreased the expression of BRCA1, betaine-homocysteine methyltransferase, CYP7B1, CYP2F2 and insulin-like growth factor-1 in normal and cancerous livers. Alterations in these gene products were associated with arsenic/TPA-induced liver tumors, regardless of sex. Thus, transplacental arsenic plus postnatal TPA exposure induced similar aberrant gene expression patterns in male and female mouse liver, which are persistent and potentially important to the mechanism of arsenic initiation of hepatocarcinogenesis. Published by Elsevier Inc. C1 NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. NCI, SAIC, Basic Res Program, Frederick, MD 21702 USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM Liu6@niehs.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 38 TC 12 Z9 13 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 15 PY 2006 VL 213 IS 3 BP 216 EP 223 DI 10.1016/j.taap.2005.10.010 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 054WQ UT WOS:000238409700004 PM 16368122 ER PT J AU Mathias, RA Gao, PS Goldstein, JL Wilson, AF Pugh, EW Furbert-Harris, P Dunston, GM Malveaux, FJ Togias, A Barnes, KC Beaty, TH Huang, SK AF Mathias, Rasika A. Gao, Peisong Goldstein, Janet L. Wilson, Alexander F. Pugh, Elizabeth W. Furbert-Harris, Paulette Dunston, Georgia M. Malveaux, Floyd J. Togias, Alkis Barnes, Kathleen C. Beaty, Terri H. Huang, Shau-Ku TI A graphical assessment of p-values from sliding window haplotype tests of association to identify asthma susceptibility loci on chromosome 11q SO BMC GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; POSITIONAL CLONING; SEQUENCE VARIANTS; GENE; GENOME; POPULATION; DISEASE; EXPRESSION; FAMILY; POLYMORPHISMS AB Background: Past work on asthmatic African American families revealed a strong linkage peak with modest evidence of association on chromosome 11q. Here, we perform tests of association for asthma and a panel of 609 SNPs in African American subjects using a sliding window approach. While efficient in screening a region of dense genotyping, this approach does create some problems: high numbers of tests, assimilating thousands of results, and questions about setting priorities on regions with association signals. Results: We present a newly developed tool, Graphical Assessment of Sliding P-values or GrASP, which uses color display to indicate the width of the sliding windows, significance of individual tests, density of SNP coverage and location of known genes that simplifies some of these issues, and use it to identify regions of interest in these data. Conclusion: We demonstrate that GrASP makes it easier to visualize, summarize and prioritize regions of interest from sliding window haplotype analysis, based jointly on the p-value from all the tests from these windows and the building of haplotypes of significance in the region. Using this approach, five regions yielded strong evidence for linkage and association with asthma, including the prior peak linkage region. C1 NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Howard Univ, Coll Med, Dept Microbiol, Baltimore, MD USA. RP Mathias, RA (reprint author), NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. EM rmathias1@mail.nih.gov; pgao1@jhmi.edu; jgold@cidr.jhmi.edu; afw@mail.nih.gov; ewp@cidr.jhmi.edu; pfurbert-harris@howard.edu; gdunston@howard.edu; floyd_malveaux@merck.com; atogias@mail.jhmi.edu; kbarnes@mail.jhmi.edu; tbeaty@jhsph.edu; skhuang@mail.jhmi.edu RI Wilson, Alexander/C-2320-2009; Huang, Shau-Ku/F-5509-2010 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI-052468, R01 AI052468] NR 48 TC 40 Z9 41 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD JUN 14 PY 2006 VL 7 AR 38 DI 10.1186/1471-2156-7-38 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 071WT UT WOS:000239635300001 PM 16774684 ER PT J AU Nathan, DG Schechter, AN AF Nathan, DG Schechter, AN TI NIH support for basic and clinical research - Biomedical researcher angst in 2006 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID RESEARCH ENTERPRISE; BUDGET C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Room D1644, Boston, MA 02115 USA. EM aschecht@helix.nih.gov OI Schechter, Alan N/0000-0002-5235-9408 NR 17 TC 15 Z9 15 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 14 PY 2006 VL 295 IS 22 BP 2656 EP 2658 DI 10.1001/jama.295.22.2656 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 052HI UT WOS:000238224000029 PM 16772630 ER PT J AU Harries, D Podgornik, R Parsegian, VA Mar-Or, E Andelman, D AF Harries, D Podgornik, R Parsegian, VA Mar-Or, E Andelman, D TI Ion induced lamellar-lamellar phase transition in charged surfactant systems SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID EQUATION-OF-STATE; HYDRATION FORCES; PHOSPHOLIPID-BILAYERS; AIR/WATER INTERFACE; FLUID MEMBRANES; LIPID-BILAYERS; WATER; BINDING; PHOSPHATIDYLSERINE; ADSORPTION AB We propose a model for the liquid-liquid (L-alpha -> L-alpha') phase transition observed in osmotic pressure measurements of certain charged lamellae-forming amphiphiles. The model free energy combines mean-field electrostatic and phenomenological nonelectrostatic interactions, while the number of dissociated counterions is treated as a variable degree of freedom that is determined self-consistently. The model, therefore, joins two well-known theories: the Poisson-Boltzmann theory for ionic solutions between charged lamellae and the Langmuir-Frumkin-Davies adsorption isotherm modified to account for charged adsorbing species. Minimizing the appropriate free energy for each interlamellar spacing, we find the ionic density profiles and the resulting osmotic pressure. While in the simple Poisson-Boltzmann theory the osmotic pressure isotherms are always smooth, we observe a discontinuous liquid-liquid phase transition when the Poisson-Boltzmann theory is self-consistently augmented by the Langmuir-Frumkin-Davies adsorption. This phase transition depends on the area per amphiphilic head group, as well as on nonelectrostatic interactions of the counterions with the lamellae and interactions between counterion-bound and counterion-dissociated surfactants. Coupling the lateral phase transition in the bilayer plane with electrostatic interactions in the bulk, our results offer a qualitative explanation for the existence of the L-alpha -> L-alpha' phase transition of didodecyldimethylammonium bromide (DDABr), but the transition's apparent absence for the chloride and the iodide homologs. More quantitative comparisons with experiment require better understanding of the microscopic basis of the phenomenological model parameters. (c) 2006 American Institute of Physics. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia. Univ Ljubljana, Dept Theoret Phys, SI-1000 Ljubljana, Slovenia. Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Phys & Astron, IL-69978 Tel Aviv, Israel. RP Harries, D (reprint author), Hebrew Univ Jerusalem, Dept Phys Chem, IL-91904 Jerusalem, Israel. EM daniel@fh.huji.ac.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 Intramural NIH HHS NR 58 TC 29 Z9 29 U1 1 U2 18 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD JUN 14 PY 2006 VL 124 IS 22 AR 224702 DI 10.1063/1.2198534 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 053BY UT WOS:000238279800044 PM 16784296 ER PT J AU Guyer, AE Nelson, EE Perez-Edgar, K Hardin, MG Roberson-Nay, R Monk, CS Bjork, JM Henderson, HA Pine, DS Fox, NA Ernst, M AF Guyer, AE Nelson, EE Perez-Edgar, K Hardin, MG Roberson-Nay, R Monk, CS Bjork, JM Henderson, HA Pine, DS Fox, NA Ernst, M TI Striatal functional alteration in adolescents characterized by early childhood behavioral inhibition SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fMRI; striatum; reward; adolescence; motivation; temperament ID DOPAMINE-RECEPTOR OVERPRODUCTION; NUCLEUS-ACCUMBENS; FRONTAL ACTIVATION; MOTIVATED BEHAVIOR; SOCIAL ANXIETY; REWARD; CHILDREN; TEMPERAMENT; ASSOCIATION; DISORDERS AB The temperamental style of behavioral inhibition has been characterized by exaggerated behavioral and neural responses to cues signaling threat. Virtually no work, however, has addressed whether behavioral inhibition may also confer heightened brain activation in response to positively valenced incentives. We used event-related functional MRI (fMRI) and a monetary incentive delay task to examine whether the neural response to incentives is also greater in adolescents characterized as behaviorally inhibited early in life compared with those characterized as non-inhibited. Whereas task performance did not differ between groups, fMRI revealed greater striatal activation to incentives in behaviorally inhibited adolescents than in non-inhibited adolescents. This was regardless of whether the incentive was an anticipated gain or loss. Alteration in neural systems underlying behavior modulated by both negative and positive contingencies may represent a correlate of behavioral inhibition that also underlies vulnerability to various forms of developmental psychopathology. C1 NIMH, Emot Dev & Affect Neurosci Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23284 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Psychol, Coral Gables, FL 33146 USA. George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. RP Guyer, AE (reprint author), 15K North Dr,Room 208, Bethesda, MD 20892 USA. EM amandaguyer@mail.nih.gov RI Perez-Edgar, Koraly/B-8463-2008; Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014; OI Perez-Edgar, Koraly/0000-0003-4051-9563; Nelson, Eric/0000-0002-3376-2453; Bjork, James/0000-0003-0593-3291 FU Intramural NIH HHS; NICHD NIH HHS [HD 17899] NR 61 TC 114 Z9 115 U1 4 U2 14 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 JUN 14 PY 2006 VL 26 IS 24 BP 6399 EP 6405 DI 10.1523/JNEUROSCI.0666-06.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 054KQ UT WOS:000238375900002 PM 16775126 ER PT J AU Daws, LC Montanez, S Munn, JL Owens, WA Baganz, NL Boyce-Rustay, JM Millstein, RA Wiedholz, LM Murphy, DL Holmes, A AF Daws, LC Montanez, S Munn, JL Owens, WA Baganz, NL Boyce-Rustay, JM Millstein, RA Wiedholz, LM Murphy, DL Holmes, A TI Ethanol inhibits clearance of brain serotonin by a serotonin transporter-independent mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE 5-HT; serotonin transporter; gene; alcohol; clearance; mouse ID IN-VIVO; ALCOHOL DEPENDENCE; RAT-BRAIN; PROMOTER POLYMORPHISM; EXTRACELLULAR-SPACE; VENTRAL HIPPOCAMPUS; 3H-SEROTONIN UPTAKE; RAPID TOLERANCE; KNOCKOUT MICE; RAPHE NEURONS AB Brain serotonin (5-HT) modulates the neural and behavioral effects of ethanol in a manner that remains poorly understood. Here we show that treatment with physiologically relevant (i.e., moderately intoxicating) doses of ethanol inhibits clearance of 5-HT from extracellular fluid in the mouse hippocampus. This finding demonstrates, in vivo, a key molecular mechanism by which ethanol modulates serotonergic neurotransmission. The 5-HT transporter (5-HTT) is the principle means of 5-HT reuptake in the brain and an obvious candidate mechanism for the effect of ethanol to inhibit 5-HT clearance. However, our second major finding was that genetic inactivation of the 5-HTT in a knock-out mouse not only failed to prevent ethanol-induced inhibition of 5- HT clearance, but actually potentiated this effect. Ethanol-induced inhibition of 5-HT clearance was also potentiated in nonmutant mice by cotreatment with a 5-HTT antagonist. Providing a link with potential behavioral manifestations of this neural phenotype, 5-HTT knock-out mice also exhibited exaggerated sensitivity to behavioral intoxication, as assayed by the sedative/hypnotic effects of ethanol. This clearly demonstrates that the 5-HTT is not necessary for the neural and behavioral effects of ethanol observed herein and that genetic or pharmacological inactivation of the 5-HTT unmasks involvement of other principle mechanisms. These data are intriguing given growing evidence implicating the 5-HTT in the pathophysiology and treatment of alcoholism and neuropsychiatric conditions frequently comorbid with alcoholism, such as depression. The present findings provide new insights into the actions of ethanol on brain function and behavior. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, Bethesda, MD 20892 USA. NIMH, NIH, Lab Clin Sci, Bethesda, MD 20892 USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, 7703 Floyd Curl Dr,MC 7756, San Antonio, TX 78229 USA. EM daws@uthscsa.edu FU Intramural NIH HHS; NIMH NIH HHS [R01-MH64489] NR 61 TC 52 Z9 52 U1 4 U2 8 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 JUN 14 PY 2006 VL 26 IS 24 BP 6431 EP 6438 DI 10.1523/JNEUROSCI.4050-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 054KQ UT WOS:000238375900006 PM 16775130 ER PT J AU Volkow, ND Wang, GJ Telang, F Fowler, JS Logan, J Childress, AR Jayne, M Ma, YM Wong, C AF Volkow, ND Wang, GJ Telang, F Fowler, JS Logan, J Childress, AR Jayne, M Ma, YM Wong, C TI Cocaine cues and dopamine in dorsal striatum: Mechanism of craving in cocaine addiction SO JOURNAL OF NEUROSCIENCE LA English DT Article DE imaging; raclopride; addiction; caudate; putamen; conditioned responses; D-2 receptors ID NUCLEUS-ACCUMBENS CORE; SEEKING BEHAVIOR; INTRAVENOUS COCAINE; HUMAN BRAIN; EXTRACELLULAR DOPAMINE; C-11 RACLOPRIDE; RHESUS-MONKEYS; DRUG-ABUSE; RATS; RELEASE AB The ability of drugs of abuse to increase dopamine in nucleus accumbens underlies their reinforcing effects. However, preclinical studies have shown that with repeated drug exposure neutral stimuli paired with the drug (conditioned stimuli) start to increase dopamine by themselves, which is an effect that could underlie drug-seeking behavior. Here we test whether dopamine increases occur to conditioned stimuli in human subjects addicted to cocaine and whether this is associated with drug craving. We tested eighteen cocaine-addicted subjects using positron emission tomography and [C-11] raclopride (dopamine D-2 receptor radioligand sensitive to competition with endogenous dopamine). We measured changes in dopamine by comparing the specific binding of [C-11] raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [C-11] raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction. Because craving is a key contributor to relapse, strategies aimed at inhibiting dopamine increases from conditioned responses are likely to be therapeutically beneficial in cocaine addiction. C1 Natl Inst Drug Abuse, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov OI Logan, Jean/0000-0002-6993-9994 FU Intramural NIH HHS; NIDA NIH HHS [DA06278-15] NR 46 TC 542 Z9 550 U1 6 U2 54 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 JUN 14 PY 2006 VL 26 IS 24 BP 6583 EP 6588 DI 10.1523/JNEUROSCI.1544-06.2006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 054KQ UT WOS:000238375900022 PM 16775146 ER PT J AU Shirai, K Saika, S Tanaka, T Okada, Y Flanders, K Ooshima, A Ohnishi, Y AF Shirai, K Saika, S Tanaka, T Okada, Y Flanders, K Ooshima, A Ohnishi, Y TI A new model of anterior subcapsular cataract: involvement of TGF beta/Smad signaling SO MOLECULAR VISION LA English DT Article ID GROWTH-FACTOR-BETA; LENS EPITHELIAL-CELLS; SMOOTH MUSCLE ACTIN; ENDOTOXIN-INDUCED UVEITIS; HUMAN AQUEOUS-HUMOR; MESENCHYMAL TRANSITION; CAPSULAR CATARACT; GENE-EXPRESSION; MICE; PROLIFERATION AB Purpose: To develop a new animal model of anterior subcapsular cataract formation by topical application of alkali to the eye and to examine the role of Transforming growth factor beta/Smad3 (TGF beta/Smad3) signaling in the formation of this cataract model. Methods: Under anesthesia, one eye of adult Wistar rats (n=142) was subjected to alkali burn by topical application of 1 N NaOH. The eye was then histologically examined at specific time intervals. Immunohistochemistry with a battery of antibodies was carried out to examine the epithelial-mesenchymal transition (EMT) in lens epithelium. Enzyme immunoassay was employed to determine the level of growth factors in aqueous humor and lens tissue. Smad3-null mice were also used to examine the role of Smad3 signaling in cataractogenesis in this model. Results: Two days post-burn of the ocular surface, lens epithelium underwent EMT as evidenced by the upregulation of Snail and alpha-smooth muscle actin and formed a multilayer of cells beneath the capsule. Smad signaling was found to be activated in EMT-type lens cells. The majority of myofibroblast-type lens cells expressed proliferative cell nuclear antigen (PCNA). The total amount of active TGF beta 2, total TGF beta 2, and Fibroblast growth factor 2 (FGF2) increased in the aqueous humor and lens. Loss of Smad3 attenuated, but did not completely abolish, EMT in the lens epithelium. Conclusions: Topical alkali treatment of the ocular surface readily induces an EMT-type anterior subcapsular cataract. Smad3 signaling is involved, but not required, for achievement of EMT in the lens epithelium in this cataract model. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama, Japan. Wakayama Med Univ, Dept Pathol, Wakayama, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Shirai, K (reprint author), Wakayama Med Univ, Dept Ophthalmol, Wakayama, Japan. EM shirai@wakayama-med.ac.jp NR 43 TC 23 Z9 28 U1 0 U2 4 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 14 PY 2006 VL 12 IS 76 BP 681 EP 691 PG 11 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 057SW UT WOS:000238616500001 PM 16807527 ER PT J AU Munoz, V Ghirlando, R Blanco, FJ Jas, GS Hofrichter, J Eaton, WA AF Munoz, Victor Ghirlando, Rodolfo Blanco, Francisco J. Jas, Gouri S. Hofrichter, James Eaton, William A. TI Folding and aggregation kinetics of a beta-hairpin SO BIOCHEMISTRY LA English DT Review ID MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY LANDSCAPE; INTRAMOLECULAR CONTACT FORMATION; STATISTICAL-MECHANICAL MODEL; STREPTOCOCCAL PROTEIN-G; SHORT LINEAR PEPTIDE; C-TERMINAL FRAGMENT; ALL-ATOM MODEL; EXPLICIT WATER; SECONDARY-STRUCTURE AB We have investigated the solution structure, equilibrium properties, and folding kinetics of a 17-residue beta-hairpin-forming peptide derived from the protein ubiquitin. NMR experiments show that at 4 degrees C the peptide has a highly populated beta- hairpin conformation. At protein concentrations higher than 0.35 mM, the peptide aggregates. Sedimentation equilibrium measurements show that the aggregate is a trimer, while NMR indicates that the beta-hairpin conformation is maintained in the trimer. The relaxation kinetics in nanosecond laser temperature-jump experiments reveal a concentration-independent microsecond phase, corresponding to beta-hairpin unfolding-refolding, and a concentration-dependent millisecond phase due to oligomerization. Kinetic modeling of the relaxation rates and amplitudes yields the folding and unfolding rates for the monomeric beta-hairpin, as well as assembly and disassembly rates for trimer formation consistent with the equilibrium constant determined by sedimentation equilibrium. When the net charge on the peptides and ionic strength were taken into account, the rate of trimer assembly approaches the Debye-Smoluchowski diffusion limit. At 300 K, the rate of formation of the monomeric hairpin is ( 17 mu s)(-1), compared to rates of ( 0.8 mu s)(-1) to ( 52 mu s)(-1) found for other peptides. After using Kramers theory to correct for the temperature dependence of the pre-exponential factor, the activation energy for hairpin formation is near zero, indicating that the barrier to folding is purely entropic. Comparisons with previously measured rates for a series of hairpins are made to distinguish between zipper and hydrophobic collapse mechanisms. Overall, the experimental data are most consistent with the zipper mechanism in which structure formation is initiated at the turn, the mechanism predicted by the Ising-like statistical mechanical model that was developed to explain the equilibrium and kinetic data for the beta-hairpin from protein GB1. In contrast, the majority of simulation studies favor a hydrophobic collapse mechanism. However, with few exceptions, there is little or no quantitative comparison of the simulation results with experimental data. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Ctr Biomol Struct & Org, College Pk, MD 20742 USA. RP Eaton, WA (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Blanco, Francisco/D-4401-2009 OI Blanco, Francisco/0000-0003-2545-4319 FU Intramural NIH HHS NR 112 TC 56 Z9 56 U1 4 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 13 PY 2006 VL 45 IS 23 BP 7023 EP 7035 DI 10.1021/bi052556a PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049WF UT WOS:000238047600004 PM 16752893 ER PT J AU Morita, H Larson, MG Barr, SC Vasan, RS O'Donnell, CJ Hirschhorn, JN Levy, D Corey, D Seidman, CE Seidman, JG Benjamin, EJ AF Morita, H Larson, MG Barr, SC Vasan, RS O'Donnell, CJ Hirschhorn, JN Levy, D Corey, D Seidman, CE Seidman, JG Benjamin, EJ TI Single-gene mutations and increased left ventricular wall thickness in the community - The Framingham Heart Study SO CIRCULATION LA English DT Article DE epidemiology; genetics; hypertrophy; myosin ID BINDING PROTEIN-C; HYPERTROPHIC CARDIOMYOPATHY; FABRY-DISEASE; AMERICAN-INDIANS; POPULATION; PREVALENCE; MASS AB Background - Mutations in sarcomere protein, PRKAG2, LAMP2, alpha-galactosidase A ( GLA), and several mitochondrial genes can cause rare familial cardiomyopathies, but their contribution to increased left ventricular wall thickness ( LVWT) in the community is unknown. Methods and Results - We studied 1862 unrelated participants ( 52% women; age, 59 +/- 9 years) from the community-based Framingham Heart Study who had echocardiograms and provided DNA samples but did not have severe hypertension, aortic prosthesis, or significant aortic stenosis. Eight sarcomere protein genes, 3 storage cardiomyopathy - causing genes, and 27 mitochondrial genes were sequenced in unrelated individuals with increased LVWT ( maximum LVWT > 13 mm). Fifty eligible participants ( 9 women) had unexplained increased LVWT. We detected 8 mutations in 9 individuals ( 2 women); 7 mutations in 5 sarcomere protein genes ( MYH7, MYBPC3, TNNT2, TNNI3, MYL3), and 1 GLA mutation. In individuals with increased LVWT, participants with sarcomere protein and storage mutations were clinically indistinguishable from those without mutations. Conclusions - In a community-based cohort, about 3% of eligible participants had increased LVWT, of whom 18% had sarcomere protein or lipid storage gene mutations. Increased LVWT in the community is a very heterogeneous condition, which sometimes may arise from single-gene variants in one of a number of genes. C1 Harvard Univ, Sch Med, Dept Genet, Cardiogenom Grp,Program Genom Applicat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. MIT, Cambridge, MA 02139 USA. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, Cardiogenom Grp,Program Genom Applicat, NRB Room 256,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM seidman@genetics.med.harvard.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [U01 HL 66582, K24-HL04334, N01-HC 25195]; NINDS NIH HHS [5R01-NS 17950] NR 23 TC 76 Z9 78 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 13 PY 2006 VL 113 IS 23 BP 2697 EP 2705 DI 10.1161/CIRCULATIONHA.105.593558 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 052HG UT WOS:000238223400007 PM 16754800 ER PT J AU He, H Wisner, P Yang, GJ Hu, HM Haley, D Miller, W O'Hara, A Alvord, WG Clegg, CH Fox, BA Urba, WJ Walker, EB AF He, Hong Wisner, Preya Yang, Guojun Hu, Hong-Ming Haley, Dan Miller, William O'Hara, Aisling Alvord, W. Gregory Clegg, Christopher H. Fox, Bernard A. Urba, Walter J. Walker, Edwin B. TI Combined IL-21 and low-dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID CD8(+) T-CELLS; IN-VIVO; ADAPTIVE IMMUNITY; SELECTIVE EXPRESSION; METASTATIC MELANOMA; ADOPTIVE TRANSFER; DENDRITIC CELLS; IFN-GAMMA; B-CELLS; MEMORY AB Background: In vivo studies have recently demonstrated that interleukin 21 (IL-21) enhances the anti-tumor function of T-cells and NK cells in murine tumor models, and the combined use of IL-21 and IL-15 has resulted in prolonged tumor regression and survival in mice with previously established tumors. However, the combined anti-tumor effects of IL-21 and low dose IL-2 have not been studied even though IL-2 has been approved for human use, and, at low dose administration, stimulates the proliferation of memory T cells, and does not significantly increase antigen-induced apoptosis or regulatory T cell (Treg) expansion. This study examined whether recombinant IL-21 alone or in combination with low-dose IL-2 could improve the in vivo anti-tumor function of nave, tumor-antigen specific CD8(+) T cells in a gp100(25-33) T cell receptor transgenic pmel murine melanoma model. Methods: Congenic C57BL/6 (Ly5.2) mice bearing subcutaneous B16F10 melanoma tumors were sublethally irradiated to induce lymphopenia. After irradiation naive pmel splenocytes were adoptively transferred, and mice were immunized with bone marrow-derived dendritic cells pulsed with human gp100(25-33) (hgp100(25-33)). Seven days after vaccination groups of mice received 5 consecutive days of intraperitoneal administration of IL-2 alone ( 20 x 10(3) IU), IL-21 alone ( 20 mu g) or IL-21 and IL-2. Control animals received no cytokine therapy. Results: IL-21 alone and IL-2 alone both delayed tumor progression, but only IL-21 significantly augmented long-term survival (20%) compared to the control group. However, combination therapy with IL-21 and IL-2 resulted in the highest long-term (> 150 days) tumor-free survival frequency of 46%. Animals that were tumor-free for > 150 days demonstrated tumor-specific protection after rechallenge with B16F10 melanoma cells. At peak expansion ( 21 days post vaccination), the combination of IL-21 plus IL-2 resulted in a 2- to 3-fold higher absolute number of circulating tumor antigen-specific pmel CD8(+) T cells than was stimulated by IL-2 or IL-21 alone. Pmel CD8(+) T cells were predominantly partitioned into central memory (CD62L(+)/CD127(+)) or effector-memory (CD62L(-)/CD127(+)) phenotypes by day 28-post vaccination in IL-21 + IL-2 treated mice. Conclusion: These observations support the potential use of IL-21 and low-dose IL-2 therapy in combination with a tumor-antigen vaccine and lymphopenic conditioning in future cancer clinical trials to maintain high numbers of anti-tumor memory CD8(+) T cells with the potential to sustain long term tumor regression and survival. C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. NCI, DMS, Frederick, MD 21701 USA. Zymogenet Inc, Immunol Res, Seattle, WA 98105 USA. RP Walker, EB (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR USA. EM hong.he@providence.org; Kpreyaa@gmail.com; guojun.yang@providence.org; hhu@providence.org; daniel.haley@providence.org; william.miller@providence.org; aohara@liai.org; gwa@css.ncifcrf.gov; cleggc@zgi.com; foxb@foxlab.org; walter.urba@providence.org; edwin.walker@providence.org FU NCI NIH HHS [R21 CA101325] NR 48 TC 45 Z9 48 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 13 PY 2006 VL 4 AR 24 DI 10.1186/1479-5876-4-24 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 064SA UT WOS:000239108200001 PM 16772043 ER PT J AU Voon, V Hassan, K Zurowski, M Duff-Canning, S de Souza, M Fox, S Lang, AE Miyasaki, J AF Voon, V Hassan, K Zurowski, M Duff-Canning, S de Souza, M Fox, S Lang, AE Miyasaki, J TI Prospective prevalence of pathologic gambling and medication association in Parkinson disease SO NEUROLOGY LA English DT Article AB The authors prospectively screened 297 patients with Parkinson disease (PD), who attended a tertiary clinic, using a modified South Oaks Gambling Scale. Lifetime prevalence of pathologic gambling (PG) was 3.4% and on any dopamine agonist was 7.2%. PG was associated with earlier PD onset and with dopamine agonists but not with agonist subtype or doses. We found no association with a potent D3 receptor agonist. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Toronto Western Hosp, Dept Psychiat, Toronto, ON M5T 2S8, Canada. Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Voon, V (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5S213,10 Ctr Dr, Bethesda, MD 20892 USA. EM voonv@ninds.nih.gov RI zurowski, mateusz/D-1536-2010; OI zurowski, mateusz/0000-0002-6407-4629; Miyasaki, Janis/0000-0002-6372-6007 NR 10 TC 190 Z9 197 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 13 PY 2006 VL 66 IS 11 BP 1750 EP 1752 DI 10.1212/01.wnl.0000218206.20920.4d PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 052HF UT WOS:000238223300031 PM 16769956 ER PT J AU Strong, MJ Yang, W Strong, WL Leystra-Lantz, C Jaffe, H Pant, HC AF Strong, MJ Yang, W Strong, WL Leystra-Lantz, C Jaffe, H Pant, HC TI Tau protein hyperphosphorylation in sporadic ALS with cognitive impairment SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; DEMENTIA AB The authors have characterized frontal cortical tau protein in cognitively intact ( 4) and cognitively impaired (ALSci, 4) ALS patients and compared it with control ( 2) or Alzheimer disease (AD,1)- derived tau. The authors observed expression of both 3R and 4R tau isoforms; increased insoluble tau protein; phosphatase resistance; and hyperphosphorylation at T175, S208, and S210. Soluble tau from both AD and ALSci was also phosphorylated at S237. Tau hyperphosphorylation is associated with ALS. C1 Robarts Res Inst, Cell Biol Res Grp, London, ON N6A 5C1, Canada. Univ Western Ontario, Schulich Sch Med, Dept Clin Neurol Sci, London, ON N6A 3K7, Canada. NINDS, NIH, Bethesda, MD 20892 USA. RP Strong, MJ (reprint author), UH, LHSC, Room C7-120, London, ON N6A 5A5, Canada. EM mstrong@uwo.ca RI Strong, Michael/H-9689-2012 NR 10 TC 30 Z9 32 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 13 PY 2006 VL 66 IS 11 BP 1770 EP 1771 DI 10.1212/01.wnl.0000218161.15834.db PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 052HF UT WOS:000238223300037 PM 16769962 ER PT J AU Basile, JR Castilho, RM Williams, VP Gutkind, JS AF Basile, JR Castilho, RM Williams, VP Gutkind, JS TI Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE head and neck cancer; c-Met protein; plexin; chemotaxis; endothelium ID ENDOTHELIAL GROWTH-FACTOR; LUNG-CANCER; FACTOR VEGF; RECEPTORS; NEUROPILIN-1; INHIBITION; MECHANISMS; CELLS; GENE; ARTERIOGENESIS AB Tumor progression and metastasis depend on the ability of cancer cells to initiate angiogenesis and ensure delivery of oxygen, nutrients, and growth factors to rapidly dividing transformed cells and provide access to the systemic circulation. In addition to well established growth factors and inflammatory mediators that promote capillary sprouting and endothelial cell growth and migration, an emerging body of evidence supports a previously unrecognized function for axon guidance molecules in regulation of blood vessel development. Here we show that semaphorin 4D (Sema4D) a protein originally shown to regulate axonal growth cone guidance in the developing central nervous system through its receptor, plexin-B1, is highly expressed in cell lines derived from head and neck squamous cell carcinomas (HNSCCs) at both the protein and message level. Immunohistochemical analysis of a large collection of HNSCC specimens revealed high levels of Sema4D in a cell surface pattern in invading islands of transformed epithelial cells, but not in normal and noninvasive dysplastic epithelium. A similar pattern was observed in malignant cells from prostate, colon, breast, and lung cancer tissues. When shed from HNSCC cells, Sema4D stimulates endothelial cell migration, which can be prevented by Sema4D-blocking antibodies and by Sema4D knockdown. Furthermore, knocking down Sema4D by lentiviral expression of Sema4D shRNA reduces dramatically the size and vascularity of HNSCC tumor xenografts. These findings indicate that expression of Sema4D is a frequently used strategy by which a wide variety of carcinomas may promote angiogenesis, and therefore is a possible therapeutic target for the treatment of these malignancies. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Meharry Med Coll, Nashville, TN 37208 USA. RP Williams, VP (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Room 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Castilho, Rogerio/E-4987-2010 NR 38 TC 132 Z9 152 U1 1 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 JUN 13 PY 2006 VL 103 IS 24 BP 9017 EP 9022 DI 10.1073/pnas.0508825103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100023 PM 16754882 ER PT J AU Hou, L Arnheiter, H Pavan, WJ AF Hou, L Arnheiter, H Pavan, WJ TI Interspecies difference in the regulation of melanocyte development by SOX10 and MITF SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neural crest; pigmentation; transcription; cell fate; neurocristopathy ID NEURAL-CREST; WAARDENBURG-SYNDROME; TRANSCRIPTIONAL REGULATION; SACCHAROMYCES-CEREVISIAE; HIRSCHSPRUNG-DISEASE; MOUSE MODEL; GENE; MICROPHTHALMIA; MUTATIONS; LINEAGE AB There is increasing indication that interspecific phenotypic differences result from variations in gene-regulatory interactions. Here we provide evidence that mice differ from zebrafish in the way they use homologous key components to regulate pigment cell differentiation. In both zebrafish and mice, one transcription factor, SOX10, controls the expression of another, MITF (microphthalmia-associated transcription factor), which in turn regulates a set of genes critical for pigment cell development and pigmentation. Mutations in either Sox10 or Mitf impair pigment cell development. In Sox10-mutant zebrafish, experimentally induced expression of Mitf fully rescues pigmentation. Using lineage-directed gene transfer, we show that, in the mouse, Mitf can rescue Sox10-mutant precursor cells only partially. In fact, retrovirally mediated, Sox10-independent Mitf expression in mouse melano-blasts leads to cell survival and expression of a number of pigment biosynthetic genes but does not lead to expression of tyrosinase, the rate-limiting pigment gene which critically depends on both Sox10 and Mitf. Hence, compared with fish, mice have evolved a regulation of tyrosinase expression that includes feed-forward loops between Sox10 and tyrosinase regulatory regions. The results may help to explain how some embryos, such as zebrafish, can achieve rapid pigmentation after fertilization, whereas others, such as mice, become pigmented only several days after birth. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA. RP Hou, L (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Bldg 49,Room 4A82, Bethesda, MD 20892 USA. EM lhou@mail.nih.gov; bpavan@nhgri.nih.gov OI Hou, Ling/0000-0003-0705-8099 NR 42 TC 45 Z9 52 U1 1 U2 2 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 JUN 13 PY 2006 VL 103 IS 24 BP 9081 EP 9085 DI 10.1073/pnas.0603114103 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100034 PM 16757562 ER PT J AU Cui, CY Hashimoto, T Grivennikov, SI Piao, YL Nedospasov, SA Schiessinger, D AF Cui, Chang-Yi Hashimoto, Tsuyoshi Grivennikov, Sergei I. Piao, Yulan Nedospasov, Sergei A. Schiessinger, David TI Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE collagen; ectodermal dysplasia; hair type; NF-kappa B; skin appendages ID ANHIDROTIC ECTODERMAL DYSPLASIA; NF-KAPPA-B/REL; EPIDERMAL DEVELOPMENT; FOLLICLE DEVELOPMENT; TNF-RECEPTOR; EDA GENE; MICE; MOUSE; EXPRESSION; PROTEIN AB Mutations in the EDA gene cause anhidrotic/hypohidrotic ectodermal dysplasia, a disorder characterized by defective formation of hair, sweat glands, and teeth in humans and in a mouse model, "Tabby" (Ta). The gene encodes ectodysplasin, a TNF ligand family member that activates the NF-kappa B-signaling pathway, but downstream targets and the mechanism of skin appendage formation have been only partially analyzed. Comparative transcription profiling of embryonic skin during hair follicle development in WT and Ta mice identified critical anhidrotic/hypohidrotic ectodermal dysplasia (EDA) effectors in four pathways, three already implicated in follicle formation. They included Shh and its effectors, as well as antagonists for the Wnt (Dkk4) and BMP (Sostdc1) pathways. The fourth pathway was unexpected, a variant NF-kappa B-signaling cascade based on lymphotoxin-beta (LT beta)/ReIB. Previously known to participate only in lymphoid organogenesis, LT beta was enriched in developing hair follicles of WT but not in Ta mice. Furthermore, in mice lacking LT beta, all three types of mouse hair were still formed, but all were structurally abnormal. Guard hairs became wavy and irregular, zigzag/auchen hairs lost their kinks, and in a phenocopy of features of Ta animals, the awl hairs doubled in number and were characteristically distorted and pinched. LT beta-null mice that received WT bone marrow transplants maintained mutant hair phenotypes, consistent with autonomous LT beta action in skin independent of its expression in lymphoid cells. Thus, as an EDA target, LT beta regulates the form of hair in developing hair follicles; and when EDA is defective, failure of LT beta activation can account for part of the Ta phenotype. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NCI, Basic Res Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. RP Schiessinger, D (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 FU Intramural NIH HHS NR 44 TC 41 Z9 45 U1 0 U2 2 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 JUN 13 PY 2006 VL 103 IS 24 BP 9142 EP 9147 DI 10.1073/pnas.0509678103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100045 PM 16738056 ER PT J AU Zhang, P Yu, MYW Venable, R Alter, HJ Shih, JWK AF Zhang, P Yu, MYW Venable, R Alter, HJ Shih, JWK TI Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hepatitis B surface antigen; neutralizing antibody ID HUMAN MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; IMMUNE GLOBULIN; PHYLOGENETIC RELATEDNESS; TUPAIA HEPATOCYTES; ATTACHMENT SITE; PRE-S(2) REGION; INFECTION; GENOTYPES; VACCINE AB Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present in ad subtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority of ay subtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype "d" epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov NR 44 TC 12 Z9 12 U1 0 U2 1 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 JUN 13 PY 2006 VL 103 IS 24 BP 9214 EP 9219 DI 10.1073/pnas.0603316103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100057 PM 16757558 ER PT J AU Le May, C Chu, K Hu, M Ortega, CS Simpson, ER Korach, KS Tsai, MJ Mauvais-Jarvis, F AF Le May, C Chu, K Hu, M Ortega, CS Simpson, ER Korach, KS Tsai, MJ Mauvais-Jarvis, F TI Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE estradiol; oxidative stress ID RECEPTOR GENE; RESISTANCE; HORMONE; 17-BETA-ESTRADIOL; DYSFUNCTION; DISRUPTION; MUTATION; ISLETS; DEATH; TRIAL AB In diabetes, the death of insulin-producing beta-cells by apoptosis leads to insulin deficiency. The lower prevalence of diabetes in females suggests that female sex steroids protect from beta-cell injury. Consistent with this hypothesis, 17 beta-estradiol (estradiol) manifests antidiabetic actions in humans and rodents. In addition, estradiol has antiapoptotic actions in cells that are mediated by the estrogen receptor-a (ER alpha), raising the prospect that estradiol antidiabetic function may be due, in part, to a protection of beta-cell apoptosis via ER alpha. To address this question, we have used mice that were rendered estradiol-deficient or estradiol-resistant by targeted disruption of aromatase (ArKO) or ER alpha (alpha ERKO) respectively. We show here that in both genders, ArKO-/- mice are vulnerable to beta-cell apoptosis and prone to insulin-deficient diabetes after exposure to acute oxidative stress with streptozotocin. In these mice, estradiol treatment rescues streptozotocin-incluced, beta-cell apoptosis, helps sustain insulin production, and prevents diabetes. In vitro, in mouse pancreatic islets and beta-cells exposed to oxidative stress, estradiol prevents apoptosis and protects insulin secretion. Estradiol protection is partially lost in beta-cells and islets treated with an ER alpha antagonist and in alpha ERKO islets. Accordingly, alpha ERKO mice are no longer protected by estradiol and display a gender nonspecific susceptibility to oxidative injury, precipitating beta-cell apoptosis and insulin-deficient diabetes. Finally, the predisposition to insulin deficiency can be mimicked in WT mice by pharmacological inhibition of ER alpha by using the antagonist tamoxifen. This study demonstrates that estradiol, acting, at least in part, through ER alpha, protects beta-cells from oxidative injury and prevents diabetes in mice of both genders. C1 Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Mauvais-Jarvis, F (reprint author), Baylor Coll Med, Dept Med, Div Endocrinol Diabet & Metab, Room 700B, Houston, TX 77030 USA. EM fmjarvis@bcm.edu RI Le May, cedric/D-2691-2009; OI Korach, Kenneth/0000-0002-7765-418X FU NIDDK NIH HHS [R21 DK069362-01, R21 DK069362] NR 24 TC 178 Z9 182 U1 1 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 JUN 13 PY 2006 VL 103 IS 24 BP 9232 EP 9237 DI 10.1073/pnas.0602956103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100060 PM 16754860 ER PT J AU Arany, PR Flanders, KC Kobayashi, T Kuo, CK Stuelten, C Desai, KV Tuan, R Rennard, SI Roberts, AB AF Arany, PR Flanders, KC Kobayashi, T Kuo, CK Stuelten, C Desai, KV Tuan, R Rennard, SI Roberts, AB TI Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TGF beta; tissue forces; wound healing ID SMOOTH MUSCLE ACTIN; TARGETED DISRUPTION; COLLAGEN GELS; NULL MICE; IN-VITRO; MODEL; FIBROBLASTS; TISSUE; MOUSE; ELASTIN AB The loss of TGF ss or its downstream mediator, Smad3, key players in tissue repair, accelerates closure of incisional wounds in mice. In contrast, we now report that excisional ear wounds in mice lacking Smad3 enlarge compared with wild-type controls resulting from changes in extracellular matrix molecules, which alter the mech-anotransduction properties of these wounds. Specifically, levels of elastin and glycosoaminoglycans are increased, collagen fibers are more compactly organized, and matrix modulators like integrins, TGF ss 1, and matrix metalloproteinases (MMPs) are altered both basally and after wounding in Smad3 knockout mice. Mechanical testing of dorsal skin correlates these changes in matrix composition with functional parameters, specifically an increased elastic modulus, suggesting an imbalance of tissue forces. We propose that the altered mechanical elastic properties translate into a persistent retractile force that is opposed by decreased wound contractile forces contributing to the enlarging ear wound in Smad3 knockout mice. These studies highlight a previously unde-scribed role for Smad3 in the mechanotransduction of matrix unsupported ear wound closure. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Pulm & Crit Care Med Sect, Dept Internal Med, Omaha, NE 68198 USA. Natl Inst Arthritis & Musculoskeletal & Skin Dis, Cartilage Biol & Orhtoped Branch, NIH, Bethesda, MD 20892 USA. RP Arany, PR (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bldg 41,Room C629,41 Lib Dr, Bethesda, MD 20892 USA. EM aranyp@mail.nih.gov; flanderk@mail.nih.gov NR 48 TC 44 Z9 48 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 JUN 13 PY 2006 VL 103 IS 24 BP 9250 EP 9255 DI 10.1073/pnas.0602473103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100063 PM 16754864 ER PT J AU Tuo, JS Ning, BT Bojanowski, CM Lin, ZN Ross, RJ Reed, GF Shen, DF Jiao, XD Zhou, M Chew, EY Kadlubar, FF Chan, CC AF Tuo, JS Ning, BT Bojanowski, CM Lin, ZN Ross, RJ Reed, GF Shen, DF Jiao, XD Zhou, M Chew, EY Kadlubar, FF Chan, CC TI Synergic effect of polymorphisms in ERCC6 5 ' flanking region and complement factor H on age-related macular degeneration predisposition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cockayne syndrome; single nucleoticle polymorphism; gene regulation; interaction; DNA repair ID BASE EXCISION-REPAIR; COCKAYNE-SYNDROME; EYE DISEASE; TRANSCRIPTION ELONGATION; FAMILIAL AGGREGATION; OXIDATIVE STRESS; RISK-FACTORS; DNA-REPAIR; MACULOPATHY; OVEREXPRESSION AB This study investigates age-related macular degeneration (AMD) genetic risk factors through identification of a functional single-nucleotide polymorphism (SNP) and its disease association. We chose ERCC6 because of its roles in the aging process, DNA repair, and ocular degeneration from the gene disruption. Bioinformatics indicated a putative binding-element alteration on the sequence containing C-6530 > G SNP in the 5 ' flanking region of ERCC6 from Sp1 on the C allele to SP1, GATA-1, and OCT-1 on the G allele. Electrophoretic mobility shift assays displayed distinctive C and G allele-binding patterns to nuclear proteins. Luciferase expression was higher in the vector construct containing the G allele than that containing the C allele. A cohort of 460 advanced AMD cases and 269 age-matched controls was examined along with pathologically diagnosed 57 AMD and 18 age-matched non-AMD archived cases. ERCC6 C-6530 > G was associated with AMD susceptibility, both independently and through interaction with an SNP (rs380390) in the complement factor H (CFH) intron reported to be highly associated with AMD. A disease odds ratio of 23 was conferred by homozygozity for risk alleles at both ERCC6 and CFH compared with homozygozity for nonrisk alleles. Enhanced ERCC6 expression was observed in lymphocytes from healthy donors bearing ERCC6 C-6530 > G alleles. Intense immunostaining of ERCC6 was also found in AMD eyes from ERCC6 C-6530 > G carriers. The strong AMD predisposition conferred by the ERCC6 and CFH SNPs may result from biological epistasis, because ERCC6 functions in universal transcription as a component of RNA pol I transcription complex. C1 NEI, Immunol Lab, Sect Immunopathol, NIH, Bethesda, MD 20892 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. NEI, Opthtalm Genet & Visual Funct Branch, Sect Ophthalm Mol Genet, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Div Phamacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. RP Chan, CC (reprint author), NEI, Immunol Lab, Sect Immunopathol, NIH, 10-10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU Intramural NIH HHS [Z99 EY999999] NR 49 TC 71 Z9 75 U1 0 U2 0 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 JUN 13 PY 2006 VL 103 IS 24 BP 9256 EP 9261 DI 10.1073/pnas.0603485103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 054ID UT WOS:000238369100064 PM 16754848 ER PT J AU Fletcher, PS Elliott, J Grivel, JC Margolis, L Anton, P McGowan, I Shattock, RJ AF Fletcher, Patricia S. Elliott, Julie Grivel, Jean-Charles Margolis, Leonid Anton, Peter McGowan, Ian Shattock, Robin J. TI Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides SO AIDS LA English DT Article DE anal intercourse; explants; gut-associated lymphoid tissue; HIV prevention; rectal mucosa; sexual transmission; topical microbicides ID HUMAN CERVICAL TISSUE; IMMUNODEFICIENCY-VIRUS; RECTAL TRANSMISSION; ORGAN-CULTURE; HIV-1 TRANSMISSION; T-CELLS; INFECTION; MODEL; INTERCOURSE; PREVENTION AB Objectives: Establishment of an in vitro model to evaluate rectal safety and the efficacy of microbicide candidates. Design: An investigation and characterization of human colorectal explant culture for screening candidate microbicides to prevent rectal transmission of HIV-1 infection. Methods: Human colorectal explants were cultured at the liquid-air interface on gelfoam rafts. Phenotypic characterization of HIV-1 target cells was performed by fluorescence-activated cell sorter analysis. HIV-1 infection was determined by the measurement of p24 antigen release, viral RNA, and proviral DNA accumulation. Results: Colorectal explant CD4 T cells expressed higher CCR5 and CXCR4 levels compared with blood. Minor differences between the rectal and sigmoid colon were observed with a trend for slightly higher CCR5 and HLA-DR expression in cells from the sigmoid colon. Favourable culture conditions were established for colorectal tissue. Although tissue structure degenerated with time, CD4 : CD8 cell ratios remained constant, and tissue supported productive HIV-1 infection. The ability of candidate microbicides to inhibit R5 HIV-1 infection was evaluated. Polyanion candidates, PRO2000 and dextrin sulphate, provided 99% protection at 1 mu g/ml and 1 mg/ml, respectively, equivalent to 1/5000 and 1/40 of the vaginal formulations. The nucleotide reverse transcriptase inhibitor (NRTI) 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) provided protection at concentrations 1000-fold lower (10 mu g/ml) than the proposed vaginal formulation (11%). Furthermore, non-NRTI UC-781 and TMC-120 provided greater than 99% inhibition at 3.3 or 0.33 mu g/ml, respectively. No products demonstrated toxicity to rectal mucosa at inhibitory concentrations. Conclusion: Colorectal explant culture was shown to be a useful tool for the preclinical evaluation of potential microbicides. The data suggest that rectally applied microbicides might provide protection from HIV-1 transmission. (c) 2006 Lippincott Williams & Wilkins. C1 St Georges Univ London, London SW17 0RE, England. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. NIH, Sect Cellular Interact, Bethesda, MD 20892 USA. RP Shattock, RJ (reprint author), St Georges Univ London, Cranmer Terrace, London SW17 0RE, England. EM shattock@sgul.ac.uk FU Intramural NIH HHS; Medical Research Council [G0100137]; NCCIH NIH HHS [AT 48002]; NIAID NIH HHS [AI 060614, AI 28697, AI 46749, AI 01610] NR 30 TC 79 Z9 82 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 JUN 12 PY 2006 VL 20 IS 9 BP 1237 EP 1245 DI 10.1097/01.aids.0000232230.96134.80 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 065SX UT WOS:000239180700003 PM 16816551 ER PT J AU Taha, TE Brown, ER Hoffman, IF Fawzi, W Read, JS Sinkala, M Martinson, FEA Kafulafula, G Msamanga, G Emel, L Adeniyi-Jones, S Goldenberg, R AF Taha, Taha E. Brown, Elizabeth R. Hoffman, Irving F. Fawzi, Wafaie Read, Jennifer S. Sinkala, Moses Martinson, Francis E. A. Kafulafula, George Msamanga, Gernard Emel, Lynda Adeniyi-Jones, Samuel Goldenberg, Robert CA HPTN 024 Team TI A phase III clinical trial of antibiotics to reduce chorioamnionitis-related perinatal HIV-1 transmission SO AIDS LA English DT Article DE Africa; antibiotics; chorioamnionitis; mother-to-child transmission of HIV-1; nevirapine; phase III clinical trial ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED CONTROLLED-TRIAL; BACTERIAL VAGINOSIS; ZIDOVUDINE; NEVIRAPINE; INFLAMMATION; INTRAPARTUM; INFECTION; UGANDA AB Objective: A multisite study was conducted in Africa to assess the efficacy of antibiotics to reduce mother-to-child transmission (MTCT) of HIV-1. Design: A randomized, double-blinded, placebo-controlled, phase III clinical trial. Methods: HIV-1-infected women were randomly assigned at 20-24 weeks' gestation to receive either antibiotics (metroniclazole plus erythromycin antenatally and metroniclazole plus ampicillin intrapartum) or placebo. Maternal study procedures were performed at 20-24, 26-30, and 36 weeks antenatally, and at labor/delivery. Infants were seen at birth, 4-6 weeks, and 3, 6, 9 and 12 months. The primary efficacy endpoints were overall infant HIV-1 infection and HIV-1-free survival at 4-6 weeks. All women and infants received single-dose nevirapine prophylaxis in this study. Results: A total of 1510 live-born infants were included in the primary analysis. The proportions of HIV-1-infected infants at birth were similar (antibiotics 7.1%; placebo 8.3%; P = 0.41). Likewise, there were no statistically significant differences at 4-6 weeks in the overall risk of MTCT of HIV-1 (antibiotics 16.2%; placebo 15.8%; P = 0.89) or HIV-1-free survival (79.4% in each study arm). Post-randomization, the proportion of women with bacterial vaginosis at the second antenatal visit was significantly lower in the antibiotics arm compared with the placebo arm (23.8 versus 39.7%; P < 0.001), but the frequency of histological chorioamnionitis was not different (antibiotics 36.9%; placebo 39.7%; P = 0.30). Adverse events in mothers and their infants did not differ by randomization arm. Conclusion: This simple antepartum and peripartum antibiotic regimen did not reduce the risk of MTCT of HIV-1. (c) 2006 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ N Carolina, Div Infect Dis, Chapel Hill, NC 27515 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Matenal AIDS Branch, Div AIDS, NIAID,NIH, Bethesda, MD 20892 USA. Ctr Infect Dis Res Zambia, Lusaka, Zambia. Univ N Carolina Project, Lilongwe, Malawi. Univ Malawi, Coll Med, Dept Obstet & Gynaecol, Blantyre, Malawi. Muhimbili Univ, Coll Hlth Sci, Dept Community Hlth, Dar Es Salaam, Tanzania. Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. RP Taha, TE (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E7138, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu RI Brown, Elizabeth/A-8984-2008 FU NIAID NIH HHS [U01 AI 48005, U01 AI 47972, N01 AI 35173, N01 AI 35173-117/412, N01 AI 45200, U01 AI 480006] NR 20 TC 46 Z9 46 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 JUN 12 PY 2006 VL 20 IS 9 BP 1313 EP 1321 DI 10.1097/01.aids.0000232240.05545.08 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 065SX UT WOS:000239180700013 PM 16816561 ER PT J AU Sharov, AA AF Sharov, Alexei A. TI Genome increase as a clock for the origin and evolution of life SO BIOLOGY DIRECT LA English DT Article ID CELLULAR-AUTOMATA; SIZE; COMPLEXITY; WORLD AB Background: The size of non-redundant functional genome can be an indicator of biological complexity of living organisms. Several positive feedback mechanisms including gene cooperation and duplication with subsequent specialization may result in the exponential growth of biological complexity in macro-evolution. Results: I propose a hypothesis that biological complexity increased exponentially during evolution. Regression of the logarithm of functional non-redundant genome size versus time of origin in major groups of organisms showed a 7.8-fold increase per 1 billion years, and hence the increase of complexity can be viewed as a clock of macro-evolution. A strong version of the exponential hypothesis is that the rate of complexity increase in early (pre-prokaryotic) evolution of life was at most the same (or even slower) than observed in the evolution of prokaryotes and eukaryotes. Conclusion: The increase of functional non-redundant genome size in macro-evolution was consistent with the exponential hypothesis. If the strong exponential hypothesis is true, then the origin of life should be dated 10 billion years ago. Thus, the possibility of panspermia as a source of life on earth should be discussed on equal basis with alternative hypotheses of de-novo life origin. Panspermia may be proven if bacteria similar to terrestrial ones are found on other planets or satellites in the solar system. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Sharov, AA (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM sharoval@mail.nih.gov NR 45 TC 13 Z9 13 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD JUN 12 PY 2006 VL 1 AR 17 DI 10.1186/1745-6150-1-17 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133SR UT WOS:000244034100001 PM 16768805 ER PT J AU Kim, EJ Kang, DO Love, DC Hanover, JA AF Kim, Eun Ju Kang, Dae Ook Love, Dona C. Hanover, John A. TI Enzymatic characterization of O-GlcNAcase isoforms using a fluorogenic GlcNAc substrate SO CARBOHYDRATE RESEARCH LA English DT Article DE O-GlcNAc; OGT; O-GlcNAcase; v-O-GlcNAcase; FDGlcNAc; MUGlcNAc; pNP-beta-GlcNAc ID BETA-N-ACETYLGLUCOSAMINIDASE; RNA-POLYMERASE-II; RAT SKELETAL-MUSCLE; LINKED GLCNAC; INSULIN-RESISTANCE; D-GLUCOSAMINIDASE; CYTOPLASMIC GLYCOPROTEINS; TETRATRICOPEPTIDE REPEATS; TRANSCRIPTION FACTORS; CYTOSOLIC PROTEINS AB A highly sensitive fluorogenic hexosaminidase substrate, fluorescein di(N-acetyl-beta-D-glucosaminide) (FDGlcNAc) was prepared essentially as described previously [Chem. Pharm. Bull. 1993, 41, 314] with some modifications. The fluorescent analog is a substrate for a number of hexosaminidases but here we have focused on the cytoplasmic O-GlcNAcase isoforms. Kinetic analysis using purified O-GlcNAcase and its splice variant (v-O-GlcNAcase) expressed in Escherichia coli suggests that FDGlcNAc is a much more efficient substrate (K-m = 84.9 mu M) than the conventional substrate, para-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside (pNP-beta-GlcNAc, K-m = 1.1 nM) and a previously developed fluorogenic substrate, 4-methylumbelliferyl 2-acetamido-2-deoxy-beta -D-glucopyranoside [MUGlcNAc, K-m = 0.43 mM; J. Biol. Chem. 2005, 280, 25313] for O-GlcNAcase. The variant O-GlcNAcase. a protein lacking the C-terminal third of the full-length O-GlcNAcase, exhibited a K-m of 2.1 mM with respect to FDGlcNAc. This shorter isoforni was not previously thought to exhibit O-GlcNAcase activity based on in vitro Studies with pNP-beta-GlcNAc. However, both O-GlcNAcase isoforms reduced O-GlcNAc protein levels extracted from HeLa and HT-29 cells in vitro. indicating that the splice variant is a bona fide O-GlcNAcase. Fluorescein di-N-acetyl-beta-D-galactosaminide (FDGalNAc) is not cleaved by these enzymes, consistent with previous findings that the O-GlcNAcase has substrate specificity toward O-GlcNAc but not O-GalNAc. The enzymatic activity of the shorter isoforni of O-GlcNAcase was first detected by using highly sensitive fluorogenic FDGlcNAc substrate. The finding that O-GlcNAcase exists as two distinct isoforms has a number of important implications for the role of O-GlcNAcase in hexosamine signaling. Published by Elsevier Ltd. C1 NIDDK, NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. Changwon Natl Univ, Coll Nat Sci, Dept Hlth Sci & Biochem, Chang Won 641773, Kyungnam, South Korea. RP Kim, EJ (reprint author), NIDDK, NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. EM eunjuk@intra.niddk.nih.gov FU PHS HHS [VFJA009594] NR 54 TC 40 Z9 41 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUN 12 PY 2006 VL 341 IS 8 BP 971 EP 982 DI 10.1016/j.carres.2006.03.004 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 046VA UT WOS:000237838000004 PM 16584714 ER PT J AU Grigorenko, B Savitsky, A Topol, I Burt, S Nemukhin, A AF Grigorenko, Bella Savitsky, Alexander Topol, Igor Burt, Stanley Nemukhin, Alexander TI trans and cis Chrornophore structures in the kindling fluorescent protein asFP595 SO CHEMICAL PHYSICS LETTERS LA English DT Article ID ELECTRONIC EXCITATIONS; CHROMOPHORE ENVIRONMENT; PROTONATION STATES; ANEMONIA-SULCATA; GFP CHROMOPHORE; CHROMOPROTEIN; QM/MM; DARK; ABSORPTION; RESOLUTION AB The ab initio QM/MM calculations are used to optimize geometry configurations of the chromophore and surrounding residues for the kindling protein asFP595. The time-dependent DFT method is applied to estimate parameters of the S(0)-S(1) vertical transition of the chromophore at the protein geometry taking into account effects from the nearest residues. The results of simulations provide a theoretical support to the hypothesis on the possibility of trans-cis izomerization of the chromophore in the mechanism of kindling. The system can absorb light in the trans anion form of the chromophore and emit at longer wavelength in the cis anion form. (c) 2006 Elsevier B.V. All rights reserved. C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. Russian Acad Sci, AN Bach Inst Biochem, Moscow 119071, Russia. NCI, Adv Biomed Comp Ctr, Ft Detrick, MD 21702 USA. RP Nemukhin, A (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. EM anem@lcc.chem.msu.ru RI Savitsky, Alexander/O-9799-2015; Nemukhin, Alexander/P-9662-2015 NR 34 TC 18 Z9 18 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD JUN 12 PY 2006 VL 424 IS 1-3 BP 184 EP 188 DI 10.1016/j.cplett.2006.04.055 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 053JL UT WOS:000238301300036 ER PT J AU Adamo, R Kovac, P AF Adamo, Roberto Kovac, Pavol TI Formation of ethyl 1-thiomannopyranosides from 2-O-chloroacetylated and 2-O-levulinoylated synthons SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE carbohydrates; synthetic methods; thioglycosides; levulinoyl protecting group; glycosylation ID METHYL ALPHA-GLYCOSIDES; VIBRIO-CHOLERAE O1; OLIGOSACCHARIDE SYNTHESIS; CHEMICAL SYNTHESIS; BETA-GLYCOSIDES; REPEATING UNIT; SEROTYPE INABA; DISACCHARIDE; DETERMINANT; ANTIGEN AB With the aim to prepare key glycosyl donors for the synthesis of fragments of the O-specific polysaccharides of Vibrio cholerae O:1, 1-O-acetyl derivatives of perosamine bearing participating 2-O-chloroacetyl or 2-O-levulinoyl groups were treated with EtSH and BF3 center dot Et2O. While poor stereoselectivity of the formation of ethyl 1-thioglycosides (alpha:beta = 3:2) was observed with 2-O-chloroacetylated intermediates, the same products can be obtained with good stereoselectivity (alpha:beta = 7:1) from 2-O-levulinoylated intermediates. Selective regeneration of the carbonyl group from dithioketals in the presence of S,O-acetals by treatment with AgNO3 and Ag2O in MeCN/H2O is also described. The conversion allows direct preparation of 1-thioglycosides from carbohydrates protected with the levulinic ester group. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. RP Adamo, R (reprint author), NIDDK, LMC, NIH, Bethesda, MD 20892 USA. NR 41 TC 5 Z9 5 U1 1 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD JUN 12 PY 2006 IS 12 BP 2803 EP 2809 DI 10.1002/ejoc.200600139 PG 7 WC Chemistry, Organic SC Chemistry GA 057NC UT WOS:000238601500016 ER PT J AU Moharram, R Maynard, D Wang, ES Makusky, A Murray, GJ Martin, BM AF Moharram, R Maynard, D Wang, ES Makusky, A Murray, GJ Martin, BM TI Reexamination of the cysteine residues in glucocerebrosidase SO FEBS LETTERS LA English DT Article DE glucocerebrosidase; SELDI; cysteine residues ID MASS-SPECTROMETRY AB Glucocerebrosidase, the deficient enzyme in Gaucher disease, catalyzes the cleavage of the P-glycosidic linkage of glucosylceramide. A previous study on the enzyme identified three disulfide bridges and a single sulfhydryl [Lee, Y., Kinoshita, H., Radke, G., Weiler, S., Barranger, J.A. and Tomich, J.M. (1995) Position of the sulfhydryl group and the disulfide bonds of human glucocerebrosidase. J. Protein Chem. 14(3), 127137] but recent publication of the X-ray structure identifies only two disulfide bridges with three free sulfhydryls [Dvir, H., Harel, M., McCarthy, A.A., Toker, L., Silman, L, Futerman, A.H. and Sussman, J.L. (2003) X-ray structure of human acid-p-glucosidase, the defective enzyme in Gaucher disease. EMBO. 4(7), 704-709]. Using chemical modifications, acid cleavage and enzymatic digestion methods, we report that three free sulfhydryls exist and that the remaining four cysteines form two disulfide bonds located within the first 25 amino-terminal residues, supporting the X-ray structure. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIMH, Unit Mol Struct, Lab Neurotoxicol, NIH,DHHS, Bethesda, MD 20892 USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH,DHHS, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Moharram, R (reprint author), NIMH, Unit Mol Struct, Lab Neurotoxicol, NIH,DHHS, 10 Ctr Dr,Bldg 10,Rm 3N309, Bethesda, MD 20892 USA. EM moharrar@mail.nih.gov FU Intramural NIH HHS NR 9 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 12 PY 2006 VL 580 IS 14 BP 3391 EP 3394 DI 10.1016/j.febslet.2006.04.096 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 053QN UT WOS:000238320100009 PM 16712845 ER PT J AU Mattapallil, JJ Douek, DC Buckler-White, A Montefiori, D Letvin, NL Nabel, GJ Roederer, M AF Mattapallil, JJ Douek, DC Buckler-White, A Montefiori, D Letvin, NL Nabel, GJ Roederer, M TI Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CELLULAR IMMUNE-RESPONSES; NEUTRALIZING ANTIBODIES; RHESUS-MONKEYS; GASTROINTESTINAL-TRACT; MONOCLONAL-ANTIBODIES; VAGINAL TRANSMISSION; CD8(+) LYMPHOCYTES; INFECTED MACAQUES; HIV-1 INFECTION AB Acute simian immunodeficiency virus ( SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Roederer, M (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM roederer@nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS; NIAID NIH HHS [AI-30034, N01AI30034] NR 48 TC 140 Z9 143 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 12 PY 2006 VL 203 IS 6 BP 1533 EP 1541 DI 10.1084/jem.20060657 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 052GC UT WOS:000238219600016 PM 16735692 ER PT J AU Cannons, JL Yu, LJ Jankovic, D Crotty, S Horai, R Kirby, M Anderson, S Cheever, AW Sher, A Schwartzberg, PL AF Cannons, JL Yu, LJ Jankovic, D Crotty, S Horai, R Kirby, M Anderson, S Cheever, AW Sher, A Schwartzberg, PL TI SAP regulates T cell-mediated help for humoral immunity by a mechanism distinct from cytokine regulation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; CD40 LIGAND EXPRESSION; NATURAL-KILLER-CELLS; MICE DEFICIENT; GENE-PRODUCT; TERMINAL DIFFERENTIATION; INFECTED CELLS; SH2 DOMAIN; B-CELLS; SLAM AB X-linked lymphoproliferative disease is caused by mutations affecting SH2D1A/SAP, an adaptor that recruits Fyn to signal lymphocyte activation molecule ( SLAM)-related receptors. After infection, SLAM-associated protein ( SAP)(-/-) mice show increased T cell activation and impaired humoral responses. Although SAP(-/-) mice can respond to T-independent immunization, we find impaired primary and secondary T-dependent responses, with defective B cell proliferation, germinal center formation, and antibody production. Nonetheless, transfer of wild-type but not SAP-deficient CD4 cells rescued humoral responses in reconstituted recombination activating gene 2(-/-) and SAP(-/-) mice. To investigate these T cell defects, we examined CD4 cell function in vitro and in vivo. Although SAP-deficient CD4 cells have impaired T cell receptor-mediated T helper ( Th)2 cytokine production in vitro, we demonstrate that the humoral defects can be uncoupled from cytokine expression defects in vivo. Instead, SAP-deficient T cells exhibit decreased and delayed inducible costimulator ( ICOS) induction and heightened CD40L expression. Notably, in contrast to Th2 cytokine defects, humoral responses, ICOS expression, and CD40L down-regulation were rescued by retroviral reconstitution with SAP-R78A, a SAP mutant that impairs Fyn binding. We further demonstrate a role for SLAM/SAP signaling in the regulation of early surface CD40L expression. Thus, SAP affects expression of key molecules required for T-B cell collaboration by mechanisms that are distinct from its role in cytokine regulation. C1 Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, San Diego, CA 92121 USA. RP Schwartzberg, PL (reprint author), Natl Human Genome Res Inst, Bethesda, MD 20892 USA. EM pams@mail.nih.gov FU Intramural NIH HHS NR 42 TC 103 Z9 108 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 12 PY 2006 VL 203 IS 6 BP 1551 EP 1565 DI 10.1084/jem.20052097 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 052GC UT WOS:000238219600018 PM 16754717 ER PT J AU Yao, WL Jiao, XD Hejtmancik, J Leske, M Hennis, A Nemesure, B AF Yao, WL Jiao, XD Hejtmancik, J Leske, M Hennis, A Nemesure, B CA Barbados Family Study Grp TI Evaluation of the association between OPA1 polymorphisms and primary open-angle glaucoma in Barbados families SO MOLECULAR VISION LA English DT Article ID NORMAL-TENSION GLAUCOMA; DOMINANT OPTIC ATROPHY; GENE; PREVALENCE; LOCUS; IDENTIFICATION; REGION; POAG; MAPS; EYE AB PURPOSE: To investigate whether single nucleotide polymorphisms (SNPs) in the OPA1 gene are associated with two primary open-angle glaucoma (POAG) subgroups: those with elevated intraocular pressure (POAG/IOP) and those with normal tension glaucoma (NTG) in the African-Caribbean population of Barbados, West Indies. METHODS: SNPs at intervening sequence (IVS) 8, +4, and +32 of the OPA1 gene were directly sequenced from 48 individuals with POAG/IOP, 48 nonglaucomatous controls, and 61 people with NTG. The remaining exons of OPA1 were screened for sequence variations in the same 48 POAG/IOP participants and 48 controls by denaturing high performance liquid chromatography (dHPLC), and identified variations were confirmed by bidirectional sequencing. Genotype and allele frequencies of all SNPs were compared for statistically significant differences using the chi(2) and Fisher's exact test. Haplotypes and compound genotypes were also analyzed to evaluate the combined effect of the two IVS8 SNPs. RESULTS: The analyses of the genotype and haplotype frequencies of IVS8 +4 and +32 do not show statistically significant differences between those with POAG/IOP or NTG and controls. At IVS8 +32, although there are suggestions of possible associations of the CC genotype with NTG (chi(2)=3.81, p=0.05), and the TC genotype with POAG/IOP (chi(2)=4.23, p=0.04), these differences do not reach statistical significance at the level of 0.017 after a Bonferroni correction. In addition, the combined genotype comparisons at IVS8 +32 do not support the association (for controls compared to NTG chi(2)=4.19, p=0.12, df=2; and for controls compared to POAG chi(2)=4.83, p=0.09, df=2). Sixteen variants are observed in the OPA1 gene, of which 10 are novel. Neither genotype nor allele frequencies of any SNP are found to be associated with POAG/IOP. CONCLUSIONS: Although some results are suggestive, there is not sufficient evidence to support an association of the SNPs evaluated in OPA1 with POAG/IOP or NTG in the African-Caribbean population of Barbados, West Indies. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Minist Hlth, Bridgetown, Barbados. Univ W Indies, Bridgetown, Barbados. RP Hejtmancik, J (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov FU PHS HHS [EYO11000] NR 20 TC 18 Z9 18 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JUN 12 PY 2006 VL 12 IS 73-75 BP 649 EP 654 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 054FR UT WOS:000238362700001 PM 16785854 ER PT J AU Borrow, R Carlone, GM Rosenstein, N Plikaytis, B Blake, M Feavers, I Martin, D Zollinger, W Robbins, J Aaberge, I Granoff, DM Miller, E van Alphen, L Poolman, J Rappuoli, R Danzig, L Hackell, J Danve, B Caulfield, M Lambert, S Stephens, D AF Borrow, R. Carlone, G. M. Rosenstein, N. Plikaytis, B. Blake, M. Feavers, I. Martin, D. Zollinger, W. Robbins, J. Aaberge, I. Granoff, D. M. Miller, E. van Alphen, L. Poolman, J. Rappuoli, R. Danzig, L. Hackell, J. Danve, B. Caulfield, M. Lambert, S. Stephens, D. TI Neisseria meningitidis group B correlates of protection and assay standardization - International meeting report Emory University, Atlanta, Georgia, United States, 16-17 march 2005 SO VACCINE LA English DT Editorial Material ID INFLUENZAE TYPE-B; MEMBRANE-VESICLE VACCINE; ESCHERICHIA-COLI K1; SERUM BACTERICIDAL ACTIVITY; TOXOID CONJUGATE VACCINE; MENINGOCOCCAL SEROGROUP-B; GROUP-C; CAPSULAR POLYSACCHARIDE; STATISTICAL CONSIDERATIONS; MONOCLONAL-ANTIBODY C1 Manchester Royal Infirm, Vaccine Evaluat Unit, Hlth Protect Agcy, Manchester M13 9WZ, Lancs, England. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Bethesda, MD 20014 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Inst Environm Sci, Porirua, New Zealand. Walter Reed Army Inst Res, Washington, DC USA. NICHHD, NIH, Bethesda, MD 20892 USA. Norwegian Inst Publ Hlth, NO-0403 Oslo, Norway. Childrens Hosp Oakland, Res Inst, Oakland, CA 94660 USA. Hlth Protect Agcy Ctr Infect, London NW9 5EQ, England. Netherlands Vaccine Inst, NL-3720 AL Bilthoven, Netherlands. GlaxoSmithKline Biol, Rixensart, Belgium. Chiron Vaccines, Siena, Italy. Chiron Vaccines, Emeryville, CA 94608 USA. Wyeth Vaccines, Pearl River, NY 10965 USA. Sanofi Pasteur, F-69280 Marcy Letoile, France. Merck & Co Inc, West Point, PA 19486 USA. WHO, CH-1211 Geneva 27, Switzerland. Emory Univ, Dept Med, Atlanta, GA 30322 USA. RP Borrow, R (reprint author), Manchester Med Microbiol Partnership, Meningococcal Reference Unit, Hlth Protect Agcy N W, Manchester Lab,Manchester Royal Infirm, POB 209,Clin Sci Bldg, Manchester M13 9WZ, Lancs, England. EM ray.borrow@hpa.org.uk RI Zollinger, Wendell/B-2887-2011 NR 101 TC 98 Z9 101 U1 0 U2 5 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 JUN 12 PY 2006 VL 24 IS 24 BP 5093 EP 5107 DI 10.1016/j.vaccine.2006.03.091 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 058BD UT WOS:000238638200001 PM 16838413 ER PT J AU Leitner, WW Bergmann-Leitner, ES Hwang, LN Restifo, NP AF Leitner, WW Bergmann-Leitner, ES Hwang, LN Restifo, NP TI Type I Interferons are essential for the efficacy of replicase-based DNA vaccines SO VACCINE LA English DT Article DE DNA vaccines; alphavirus; type IIFN; tumor therapy ID PLASMACYTOID DENDRITIC CELLS; HERPES-SIMPLEX-VIRUS; ADAPTIVE IMMUNITY; VIRAL-INFECTION; TUMOR REJECTION; CPG MOTIFS; INNATE; ACTIVATION; ANTIGEN; RNA AB The immunogenicity and efficacy of nucleic acid vaccines can be greatly enhanced when antigen production is under the control of an alphaviral replicase enzyme. However, replicase-mediated mRNA overproduction does not necessarily result in enhanced antigen level. Instead, the strong adaptive immune response of alphavirus replicon-based vectors is due to their production of double-stranded RNA (dsRNA) intermediates, which trigger innate immunity. Because viral infections are known to trigger innate immune responses that lead to the rapid production of Type I Interferons (IFNs), namely IFN-alpha and IFN-beta, we investigated the role of Type I IFNs in the enhanced immunogenicity of replicase-based DNA vaccines. In vitro, cells transfected with replicase-based plasmids produce significantly more Type I IFNs than cells transfected with a conventional DNA plasmid. In vivo, replicase-based DNA vaccines yield stronger humoral responses in the absence of Type I IFN signaling but the lack of this signaling pathway in IFN-alpha beta receptor-/- (knockout) mice abolishes T cell mediated efficacy against tumors of both conventional and alphavirus replicase-based DNA vaccines. Moreover, the co-delivery of an IFN alpha-encoding plasmid significantly improved the efficacy of a weakly immunogenic conventional plasmid. These results suggest a central role for Type I IFNs in the mechanism of replicase-based DNA vaccines and indicate that vaccines can be enhanced by enabling their capacity to triggering innate anti-viral defense pathways. Published by Elsevier Ltd. C1 NCI, Dermatol Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. RP Leitner, WW (reprint author), NCI, Dermatol Branch, Clin Res Ctr, NIH, Rm 12N238, Bethesda, MD 20892 USA. EM wolfgang_leitner@nih.gov; restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; Bergmann-Leitner, Elke/B-3548-2011; Leitner, Wolfgang/F-5741-2011; OI Bergmann-Leitner, Elke/0000-0002-8571-8956; Leitner, Wolfgang/0000-0003-3125-5922; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 51 TC 39 Z9 42 U1 1 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 JUN 12 PY 2006 VL 24 IS 24 BP 5110 EP 5118 DI 10.1016/j.vaccine.2006.04.059 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 058BD UT WOS:000238638200003 PM 16725231 ER PT J AU Yang, W AF Yang, W TI Poor base stacking at DNA lesions may initiate recognition by many repair proteins SO DNA REPAIR LA English DT Review DE BER; NER; MMR; base unstacking; lesion; recognition; proofreading ID ESCHERICHIA-COLI DNA; DOUBLE-STRANDED DNA; MISMATCH-REPAIR; EXCISION-REPAIR; CRYSTAL-STRUCTURE; DAMAGED DNA; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; CONFORMATIONAL FLEXIBILITY; ACTIVE-SITE; ABASIC DNA AB A fundamental question in DNA repair is how a mismatched or modified base is detected when embedded in millions to billions of normal base pairs. A survey of the literature and structural database reveals a common feature in all repair protein-DNA complexes: the DNA double helix is discontinuous at a lesion site due to base unstacking, kinking and/or nucleotide extrusion. Lesions induce destabilization and distortion of short linear DNAs, and underwinding in negatively supercoiled DNA presumably could compound the reduced stability caused by a lesion. A hypothesis is thus put forward that DNA lesion recognition occurs in two steps. Repair proteins initially recognize the weakened base stacking, and thus a flexible hinge at a DNA lesion. Sampling of flexible hinges rather than all DNA base pairs can reduce the task of finding a lesion by two to three orders of magnitude, from searching millions base pairs to thousands. After the initial encounter, a repair protein scrutinizes the shape, hydrogen bonding and electrostatic potentials of bases at the flexible hinge and dissociates if it is not a correct substrate. MutS, which has a broad range of substrates, actively dissociates from non-specific binding via an ATP-dependent proofreading mechanism. A single lesion may thus be sampled by BER, NER and MMR proteins until repaired. This proposition immediately suggests a mechanism for crosstalk between different repair and signaling pathways. It also raises the possibility that sampling of a lesion by one protein could facilitate loading of another by direct protein-protein or DNA mediated interactions. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM Wei.Yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU Intramural NIH HHS NR 87 TC 68 Z9 69 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD JUN 10 PY 2006 VL 5 IS 6 BP 654 EP 666 DI 10.1016/j.dnarep.2006.02.004 PG 13 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 053MT UT WOS:000238309900002 PM 16574501 ER PT J AU Liu, WL Chen, L Zhu, JC Rodgers, GP AF Liu, WL Chen, L Zhu, JC Rodgers, GP TI The glycoprotein hGC-1 binds to cadherin and lectins SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE human granulocyte colony stimulating factor stimulated; clone-1 (hGC-1); adhesion; cadherin; lectin; ricinus communis agglutinin I; (RCA i) ID OPEN-ANGLE GLAUCOMA; DIFFERENTIALLY EXPRESSED GENES; TRABECULAR MESHWORK CELLS; DISULFIDE BOND USE; EXTRACELLULAR-MATRIX; OLFACTOMEDIN-DOMAIN; SECRETED GLYCOPROTEIN; PHYLOGENETIC ANALYSIS; IN-VITRO; IDENTIFICATION AB Human granulocyte colony stimulating factor stimulated clone-1 (hGC-1, also known as GW112, OLM4, and hOlfD) is an olfactomedin-related glycoprotein of unknown function. We performed a series of biochemical studies to characterize its function. Using hGC-1 purified from baculovirus Sf9 cells we demonstrated that hGC-1 is a secreted glycoprotein containing N-linked carbohydrate chains and forms disulfide-bonded multimers. It binds to cell surfaces and to the locutions ricinus communis agglutinin I, concanavalin A and wheat germ agglutinin. Purified hGC-1 enhanced NIH3T3 and 293T/17 cell spreading and attachment, as did hGC-1-enriched culture supernatants of 293T/17 cells transfected with an hGC-1 expression vector. Coimmunoprecipitation studies demonstrated that hGC-1 interacts with cadherin in 293T/17 cells. This interaction depends on the C-terminal olfactomedin domain, but does not require the five well-conserved cysteine residues. However, cysteine residues at 83, 85, 246 and 437 are essential for secretion, and cysteine 226 is critical for hGC-1 multimer formation. Our studies demonstrated that hGC-1, an extracellular matrix glycoprotein, facilitates cell adhesion. Its potential interaction with endogenous cell surface lectins and cadherin may mediate this function. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room,9N119,9000 Rockville Pike, Bethesda, MD 20892 USA. EM gr5n@nih.gov NR 38 TC 49 Z9 53 U1 0 U2 5 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN 10 PY 2006 VL 312 IS 10 BP 1785 EP 1797 DI 10.1016/j.yexcr.2006.02.011 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 051RT UT WOS:000238179100009 PM 16566923 ER PT J AU Colevas, AD AF Colevas, AD TI Chemotherapy options for patients with metastatic or recurrent squamous cell carcinoma of the head and neck SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PHASE-II TRIAL; COOPERATIVE-ONCOLOGY-GROUP; DOCETAXEL PLUS 5-FLUOROURACIL; RECEPTOR MONOCLONAL-ANTIBODY; QUALITY-OF-LIFE; 2 DOSE LEVELS; RANDOMIZED-TRIAL; COMBINATION CHEMOTHERAPY; WEEKLY PACLITAXEL; BREAST-CANCER AB The purpose of this review is to provide readers with guidance concerning treatment of patients with advanced, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in the context of clinical trial data, We discuss issues surrounding the treatment of patients with SCCHN, with an emphasis on recommendations based on results from phase II and III clinical trials published since 1980. Many options exist for the treatment of patients with SCCHN. The most important decisions involve determining which patients are in need of treatment and which are most likely to benefit from treatment, Although many chemotherapy treatments have been shown to induce responses, survival improvement remains an unfulfilled goal. Definitive data do not exist on the effects of chemotherapy on quality of life or progression-free survival as measures of clinical benefit in this setting. Performance status, history of prior treatment, extent of tumor, and need for palliation are the most important factors in the decision to treat a patient with chemotherapy for incurable SCCHN. Single-agent treatment with conventional doses of methotrexate remains a standard for most patients with advanced, recurrent or metastatic SCCHN. Cisplatin plus fluorouracil, cisplatin plus a taxane, and single-agent taxane are the most widely studied alternatives. There is a need for further trials with end points other than overall survival or tumor response in this patient population. Guidelines for patient selection and treatment options are provided. C1 NCI, Invest Drug Branch, Canc Therapy Evlauat Program, NIH, Bethesda, MD 20892 USA. RP Colevas, AD (reprint author), Execut Plaza N,Room 7131,6130 Execut Blvd, Rockville, MD 20852 USA. EM colevasd@ctep.nci.nih.gov NR 102 TC 117 Z9 118 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2006 VL 24 IS 17 BP 2644 EP 2652 DI 10.1200/JCO.2005.05.3348 PG 9 WC Oncology SC Oncology GA 054MB UT WOS:000238379900008 PM 16763278 ER PT J AU Liu, ZH Yang, XZ Tan, F Cullion, K Thiele, CJ AF Liu, ZH Yang, XZ Tan, F Cullion, K Thiele, CJ TI Molecular cloning and characterization of human Castor, a novel human gene upregulated during cell differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Castor; CASZ1; transcription factor; cell differentiation; zinc finger; neuroblastoma; promoter ID FACTOR-BINDING SITES; NERVOUS-SYSTEM; DROSOPHILA-CASTOR; EXPRESSION; INDUCTION; DIVERSITY; DATABASE; CNS AB Castor is a zinc finger transcription factor that controls cell fate within neuroblast cell lineages in Drosophila melanogaster. Here, we describe the cloning and characterization of a human castor gene (CASZ1) that is structurally homologous to Drosophila castor. We find the expression of castor gene is increased when cells of neural origin as well as mesenchymal origin are induced to differentiation. CASZ1 is expressed in a number of normal tissues and exists in at least two mRNA species of 4.4 and 8.0 kb. They are named hCas-75 and hCasz11 because the predicted proteins have 5 and 11 zinc fingers, respectively. Deletion analysis of the proximal 5'-flanking sequences delineates sequences sufficient to drive transcription in cells of neural and non-neural origin. Both hCasz5 and hCasz11 localize predominantly in the nucleus, consistent with their role as Zn-finger containing transcription factor. CASZ1 is expressed in a number of human tumors and localizes to a chromosomal region frequently lost in tumors of neuroectodermal origin. Published by Elsevier Inc. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM ct47a@nih.gov FU Intramural NIH HHS NR 20 TC 27 Z9 31 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 9 PY 2006 VL 344 IS 3 BP 834 EP 844 DI 10.1016/j.bbrc.2006.03.207 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 043FI UT WOS:000237585000020 PM 16631614 ER PT J AU Oram, SW Liu, XX Lee, TL Chan, WY Lau, YFC AF Oram, Shane W. Liu, Xing Xing Lee, Tin-Lap Chan, Wai-Yee Lau, Yun-Fai Chris TI TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells SO BMC CANCER LA English DT Article ID HUMAN Y-CHROMOSOME; TESTIS-SPECIFIC PROTEIN; TGF-BETA-1 TARGET DENTT; HUMAN PROSTATE-CANCER; MYELOID LEUKEMOGENESIS; GONADOBLASTOMA LOCUS; EXPRESSION ANALYSIS; PUTATIVE ONCOGENE; CANDIDATE GENE; GERM-CELLS AB Background: TSPY is a repeated gene mapped to the critical region harboring the gonadoblastoma locus on the Y chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Elevated levels of TSPY have been observed in gonadoblastoma specimens and a variety of other tumor tissues, including testicular germ cell tumors, prostate cancer, melanoma, and liver cancer. TSPY contains a SET/NAP domain that is present in a family of cyclin B and/or histone binding proteins represented by the oncoprotein SET and the nucleosome assembly protein 1 (NAP1), involved in cell cycle regulation and replication. Methods: To determine a possible cellular function for TSPY, we manipulated the TSPY expression in HeLa and NIH3T3 cells using the Tet-off system. Cell proliferation, colony formation assays and tumor growth in nude mice were utilized to determine the TSPY effects on cell growth and tumorigenesis. Cell cycle analysis and cell synchronization techniques were used to determine cell cycle profiles. Microarray and RT-PCR were used to investigate gene expression in TSPY expressing cells. Results: Our findings suggest that TSPY expression increases cell proliferation in vitro and tumorigenesis in vivo. Ectopic expression of TSPY results in a smaller population of the host cells in the G(2)/M phase of the cell cycle. Using cell synchronization techniques, we show that TSPY is capable of mediating a rapid transition of the cells through the G(2)/M phase. Microarray analysis demonstrates that numerous genes involved in the cell cycle and apoptosis are affected by TSPY expression in the HeLa cells. Conclusion: These data, taken together, have provided important insights on the probable functions of TSPY in cell cycle progression, cell proliferation, and tumorigenesis. C1 Univ Calif San Francisco, VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Dept Med, Lab Cell & Dev Genet, San Francisco, CA 94121 USA. RP Lau, YFC (reprint author), Univ Calif San Francisco, VA Med Ctr, Dept Med, San Francisco, CA 94143 USA. EM shane_oram@yahoo.com; xxliu@hotmail.com; leetl@mail.nih.gov; chanwy@mail.nih.gov; chris.lau@ucsf.edu RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 FU Intramural NIH HHS NR 54 TC 66 Z9 69 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 9 PY 2006 VL 6 BP 1 EP 15 AR 154 DI 10.1186/1471-2407-6-154 PG 15 WC Oncology SC Oncology GA 071NU UT WOS:000239609700001 PM 16762081 ER PT J AU Zhao, B Li, YF Buono, C Waldo, SW Jones, NL Mori, M Kruth, HS AF Bin Zhao Li, Yifu Buono, Chiara Waldo, Stephen W. Jones, Nancy L. Mori, Masahiro Kruth, Howard S. TI Constitutive receptor-independent low density lipoprotein uptake and cholesterol accumulation by macrophages differentiated from human monocytes with macrophage-colony-stimulating factor (M-CSF) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOAM CELL-FORMATION; MEDIATED ENDOCYTOSIS; FAMILIAL HYPERCHOLESTEROLEMIA; ATHEROSCLEROTIC LESIONS; SCAVENGER RECEPTOR; CULTURED-CELLS; EXPRESSION; APOPTOSIS; MICE; MACROPINOCYTOSIS AB Recently, we have shown that macrophage uptake of low density lipoprotein (LDL) and cholesterol accumulation can occur by nonreceptor mediated fluid-phase macropinocytosis when macrophages are differentiated from human monocytes in human serum and the macrophages are activated by stimulation of protein kinase C (Kruth, H. S., Jones, N. L., Huang, W., Zhao, B., Ishii, I., Chang, J., Combs, C. A., Malide, D., and Zhang, W. Y. ( 2005) J. Biol. Chem. 280, 2352 - 2360). Differentiation of human monocytes in human serum produces a distinct macrophage phenotype. In this study, we examined the effect on LDL uptake of an alternative macrophage differentiation phenotype. Differentiation of macrophages from human monocytes in fetal bovine serum with macrophage-colony-stimulating factor (M-CSF) produced a macrophage phenotype demonstrating constitutive fluid-phase uptake of native LDL leading to macrophage cholesterol accumulation. Fluid-phase endocytosis of LDL by M-CSF human macrophages showed non-saturable uptake of LDL that did not down-regulate over 48 h. LDL uptake was mediated by continuous actin-dependent macropinocytosis of LDL by these M-CSF-differentiated macrophages. M-CSF is a cytokine present within atherosclerotic lesions. Thus, macropinocytosis of LDL by macrophages differentiated from monocytes under the influence of M-CSF is a plausible mechanism to account for macrophage foam cell formation in atherosclerotic lesions. This mechanism of macrophage foam cell formation does not depend on LDL modification or macrophage receptors. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Rm 5N-113,10 Ctr Dr,MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL-41990] NR 41 TC 47 Z9 47 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 9 PY 2006 VL 281 IS 23 BP 15757 EP 15762 DI 10.1074/jbc.M510714200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049DM UT WOS:000237996000023 PM 16606620 ER PT J AU Prabakaran, P Gan, JH Feng, Y Zhu, ZY Choudhry, V Xiao, XD Ji, XH Dimitrov, DS AF Prabakaran, P Gan, JH Feng, Y Zhu, ZY Choudhry, V Xiao, XD Ji, XH Dimitrov, DS TI Structure of severe acute respiratory syndrome coronavirus receptor-binding domain complexed with neutralizing antibody SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ANGIOTENSIN-CONVERTING ENZYME-2; COV S-GLYCOPROTEIN; SARS CORONAVIRUS; POTENT NEUTRALIZATION; SPIKE PROTEIN; VIRUS; IDENTIFICATION; VACCINES; CELLS AB The severe acute respiratory syndrome coronavirus (SARS-CoV, or SCV), which caused a world-wide epidemic in 2002 and 2003, binds to a receptor, angiotensin-converting enzyme 2 (ACE2), through the receptor-binding domain (RBD) of its envelope (spike, S) glycoprotein. The RBD is very immunogenic; it is a major SCV neutralization determinant and can elicit potent neutralizing antibodies capable of out- competing ACE2. However, the structural basis of RBD immunogenicity, RBD-mediated neutralization, and the role of RBD in entry steps following its binding to ACE2 have not been elucidated. By mimicking immune responses with the use of RBD as an antigen to screen a large human antibody library derived from healthy volunteers, we identified a novel potent cross-reactive SCV-neutralizing monoclonal antibody, m396, which competes with ACE2 for binding to RBD, and determined the crystal structure of the RBD-antibody complex at 2.3-angstrom resolution. The antibody-bound RBD structure is completely defined, revealing two previously unresolved segments (residues 376-381 and 503-512) and a new disulfide bond (between residues 378 and 511). Interestingly, the overall structure of the m396-bound RBD is not significantly different from that of the ACE2-bound RBD. The antibody epitope is dominated by a 10-residue-long protruding beta 6-beta 7 loop with two putative ACE2-binding hotspot residues (Ile-489 and Tyr-491). These results provide a structural rationale for the function of a major determinant of SCV immunogenicity and neutralization, the development of SCV therapeutics based on the antibody paratope and epitope, and a retrovaccinology approach for the design of anti-SCV vaccines. The available structural information indicates that the SCV entry may not be mediated by ACE2-induced conformational changes in the RBD but may involve other conformational changes or/and yet to be identified coreceptors. C1 NCI, Prot Interact Grp, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Biomol Struct Sect, MCL, NIH, POB B,Bldg 539,Rm 124, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012; Ponraj, Prabakaran/D-6325-2011 OI Ji, Xinhua/0000-0001-6942-1514; FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01-CO-24000] NR 40 TC 56 Z9 60 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 JUN 9 PY 2006 VL 281 IS 23 BP 15829 EP 15836 DI 10.1074/jbc.M600697200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 049DM UT WOS:000237996000031 PM 16597622 ER PT J AU Kubelka, J Chiu, TK Davies, DR Eaton, WA Hofrichter, J AF Kubelka, J Chiu, TK Davies, DR Eaton, WA Hofrichter, J TI Sub-microsecond protein folding SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein crystallography; protein folding kinetics ID VILLIN HEADPIECE SUBDOMAIN; INTRAMOLECULAR CONTACT FORMATION; SUBUNIT-BINDING DOMAIN; SPEED LIMIT; ENERGY LANDSCAPE; TEMPERATURE-JUMP; DENATURED STATE; MAXIMUM RATE; FAST EVENTS; KINETICS AB We have investigated the structure, equilibria, and folding kinetics of an engineered 35-residue subdomain of the chicken villin headpiece, an ultrafast-folding protein. Substitution of two buried lysine residues by norleucine residues stabilizes the protein by 1 kcal/mol and increases the folding rate sixfold, as measured by nanosecond laser T-jump. The folding rate at 300 K is (0.7 mu s)(-1) with little or no temperature dependence, making this protein the first sub-microsecond folder, with a rate only twofold slower than the theoretically predicted speed limit. Using the 70 ns process to obtain the effective diffusion coefficient, the free energy barrier height is estimated from Kramers theory to be less than similar to 1 kcal/mol. X-ray crystallographic determination at 1 angstrom resolution shows no significant change in structure compared to the single-norleucine-substituted molecule and suggests that the increased stability is electrostatic in origin. The ultrafast folding rate, very accurate X-ray structure, and small size make this engineered villin subdomain an ideal system for simulation by atomistic molecular dynamics with explicit solvent. Published by Elsevier Ltd. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Wyoming, Dept Chem, Laramie, WY 82071 USA. RP Eaton, WA (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov; jameshof@niddk.nih.gov NR 47 TC 156 Z9 161 U1 1 U2 24 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 9 PY 2006 VL 359 IS 3 BP 546 EP 553 DI 10.1016/j.jmb.2006.03.034 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 053IC UT WOS:000238297800005 PM 16643946 ER PT J AU Woolhead, CA Johnson, AE Bernstein, HD AF Woolhead, CA Johnson, AE Bernstein, HD TI Translation arrest requires two-way communication between a nascent polypeptide and the ribosome SO MOLECULAR CELL LA English DT Article ID OPEN READING FRAME; DECARBOXYLASE MESSENGER-RNA; ESCHERICHIA-COLI; TRYPTOPHAN INDUCTION; ANGSTROM RESOLUTION; MEMBRANE-PROTEINS; OPERON EXPRESSION; LEADER PEPTIDE; EXIT TUNNEL; SEQUENCE AB When the export of E. coli Sects is blocked, a 17 amino acid motif near the C terminus of the protein induces a translation arrest from within the ribosome tunnel. Here we used a recently described application of fluorescence resonance energy transfer (FRET) to gain insight into the mechanism of translation arrest. We found that the Sects C terminus adopted a compact conformation upon synthesis of the arrest motif. This conformational change did not occur spontaneously, but rather was induced by the ribosome. Translation arrest required both compaction of the Sects C terminus and the presence of key residues in the arrest motif. Further analysis showed that the arrested peptidyl-tRNA was resistant to puromycin treatment and revealed additional changes in the ribosome-nascent Sects complex. Based on these observations, we propose that translation arrest results from a series of reciprocal interactions between the ribosome and the C terminus of the nascent Sects polypeptide. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Syst Hlth Sci Ctr, Dept Mol & Cellular Med, College Stn, TX 77843 USA. Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov RI Johnson, Arthur/G-3457-2012 FU Intramural NIH HHS; NIGMS NIH HHS [GM26494] NR 38 TC 84 Z9 84 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 9 PY 2006 VL 22 IS 5 BP 587 EP 598 DI 10.1016/j.molcel.2006.05.021 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054JG UT WOS:000238372000004 PM 16762832 ER PT J AU Qiu, Y Zhao, YM Becker, M John, S Parekh, BS Huang, SM Hendarwanto, A Martinez, ED Chen, Y Lu, HX Adkins, NL Stavreva, DA Wiench, M Georgel, PT Schiltz, RL Hager, GL AF Qiu, Y Zhao, YM Becker, M John, S Parekh, BS Huang, SM Hendarwanto, A Martinez, ED Chen, Y Lu, HX Adkins, NL Stavreva, DA Wiench, M Georgel, PT Schiltz, RL Hager, GL TI HDAC1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription SO MOLECULAR CELL LA English DT Article ID HISTONE DEACETYLASE INHIBITION; TUMOR VIRUS PROMOTER; LONG TERMINAL REPEAT; SODIUM-BUTYRATE; GLUCOCORTICOID-RECEPTOR; LIVING CELLS; TRICHOSTATIN-A; IN-VIVO; EXPRESSION; CHROMATIN AB Although histone deacetylases (HDACs) are generally viewed as corepressors, we show that HDAC1 serves as a coactivator for the glucocorticoid receptor (GR). Furthermore, a subfraction of cellular HDAC1 is acetylated after association with the GR, and this acetylation event correlates with a decrease in promoter activity. HDAC1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. Acetylation of purified HDAC1 inactivates its deacetylase activity, and mutation of the critical acetylation sites abrogates HDAC1 function in vivo. We propose that hormone activation of the receptor leads to progressive acetylation of HDAC1 in vivo, which in turn inhibits the deacetylase activity of the enzyme and prevents a deacetylation event that is required for promoter activation. These findings indicate that HDAC1 is required for the induction of some genes by the GR, and this activator function is dynamically modulated by acetylation. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46221 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Marshall Univ, Dept Biol Sci, Huntington, WV 25755 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,B602, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA 107943] NR 41 TC 111 Z9 112 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 9 PY 2006 VL 22 IS 5 BP 669 EP 679 DI 10.1016/j.molcel.2006.04.019 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054JG UT WOS:000238372000011 PM 16762839 ER PT J AU Zofall, M Grewal, SIS AF Zofall, M Grewal, SIS TI Swi6/HP1 recruits a JmjC domain protein to facilitate transcription of heterochromatic repeats SO MOLECULAR CELL LA English DT Article ID H3 LYSINE-9 METHYLATION; FISSION YEAST CENTROMERES; HISTONE H3; SCHIZOSACCHAROMYCES-POMBE; CHROMODOMAIN PROTEIN; EPIGENETIC CONTROL; MAMMALIAN CHROMATIN; UBIQUITIN LIGASE; GENE-EXPRESSION; RNA-POLYMERASE AB Heterochromatin formation is generally thought to result in transcriptional repression of target loci. However, RNAi-mediated heterochromatin assembly requires RNA polymerase II (Pol II) transcription. The mechanism facilitating Pol II accessibility to heterochromatin is unknown. We show that the fission yeast Epe1, a JmjC domain-containing protein and a negative regulator of heterochromatin, is distributed across all major heterochromatic domains and at certain meiotic genes. Remarkably, Epe1 is recruited to heterochromatic loci by the heterochromatin protein Swi6/HP1. Moreover, Epe1 acts in a heterochromatin-specific context to promote Pol II accessibility by counteracting repressive chromatin. This requires Epe1's JmjC domain, although the mechanism utilized might be distinct from other JmjC proteins that possess known demethylase activities. We also find that Epe1 is preferentially recruited to inverted repeats flanking centromeres to restrain the spread of pericentromeric heterochromatin. Our analyses suggest that Swi6/HP1 recruits opposing chromatin-modifying activities, the balancing of which is crucial for heterochromatin maintenance. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU Intramural NIH HHS NR 54 TC 98 Z9 99 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN 9 PY 2006 VL 22 IS 5 BP 681 EP 692 DI 10.1016/j.molcel.2006.05.010 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 054JG UT WOS:000238372000012 PM 16762840 ER PT J AU Best, RB Hummer, G AF Best, RB Hummer, G TI Diffusive model of protein folding dynamics with Kramers turnover in rate SO PHYSICAL REVIEW LETTERS LA English DT Article ID ACTIVATED RATE-PROCESSES; VISCOSITY DEPENDENCE; KINETICS; FUNNELS; ENERGY; SIMULATIONS AB We study the folding kinetics of a three-helix bundle protein using a coarse polymer model. The folding dynamics can be accurately represented by one-dimensional diffusion along a reaction coordinate selected to capture the transition state. By varying the solvent friction, we show that position-dependent diffusion coefficients are determined by microscopic transitions on a rough energy landscape. A maximum in the folding rate at intermediate friction is explained by "Kramers turnover" in these microscopic dynamics that modulates the rate via the diffusion coefficient; overall folding remains diffusive even close to zero friction. For water friction, we find that the "attempt frequency" (or "speed limit") in a Kramers model of folding is about 2 mu s(-1), with an activation barrier of about 2k(B)T, and a folding transition path duration of approximate to 100 ns, 2 orders of magnitude less than the folding time of approximate to 10 mu s. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Best, RB (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM best@helix.nih.gov; hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 FU Intramural NIH HHS NR 33 TC 89 Z9 89 U1 0 U2 20 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD JUN 9 PY 2006 VL 96 IS 22 AR 228104 DI 10.1103/PhysRevLett.96.228104 PG 4 WC Physics, Multidisciplinary SC Physics GA 051LA UT WOS:000238161400061 PM 16803349 ER PT J AU Letvin, NL Mascola, JR Sun, Y Gorgone, DA Buzby, AP Xu, L Yang, ZY Chakrabarti, B Rao, SS Schmitz, JE Montefiori, DC Barker, BR Bookstein, FL Nabel, GJ AF Letvin, NL Mascola, JR Sun, Y Gorgone, DA Buzby, AP Xu, L Yang, ZY Chakrabarti, B Rao, SS Schmitz, JE Montefiori, DC Barker, BR Bookstein, FL Nabel, GJ TI Preserved CD4(+) central memory T cells and survival in vaccinated SIV-challenged monkeys SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY VIRUS SIVMAC239; RHESUS-MONKEYS; ANTIRETROVIRAL THERAPY; VIRAL REPLICATION; IMMUNE-RESPONSES; INFECTION; LYMPHOCYTES; ENVELOPE; AIDS; GAG AB Vaccine-induced cellular immunity controls virus replication in simian immunodeficiency virus (SIV) - infected monkeys only transiently, leading to the question of whether such vaccines for AIDS will be effective. We immunized monkeys with plasmid DNA and replication-defective adenoviral vectors encoding SIV proteins and then challenged them with pathogenic SIV. Although these monkeys demonstrated a reduction in viremia restricted to the early phase of SIV infection, they showed a prolonged survival. This survival was associated with preserved central memory CD4(+) T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Washington, Dept Stat, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Vienna, Dept Anthropol, A-1010 Vienna, Austria. RP Letvin, NL (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM nletvin@bidmc.harvard.edu OI Barker, Brianne/0000-0001-6932-479X FU Intramural NIH HHS [Z99 AI999999] NR 22 TC 283 Z9 289 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 9 PY 2006 VL 312 IS 5779 BP 1530 EP 1533 DI 10.1126/science.1124226 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 050XT UT WOS:000238124100050 PM 16763152 ER PT J AU Masseroli, M Kilicoglu, H Lang, FM Rindflesch, TC AF Masseroli, Marco Kilicoglu, Halil Lang, Francois-Michel Rindflesch, Thomas C. TI Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease SO BMC BIOINFORMATICS LA English DT Article ID BIOMEDICAL TEXT; PROTEIN INTERACTIONS; PARKINSONS-DISEASE; INFORMATION; DATABASE; KNOWLEDGE; SYSTEM; ANNOTATION; PARSER AB Background: Genomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease. Results: The filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing. In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease in several important databases on genetic disorders. Conclusion: Information based on the proximity postprocessing method we suggest is of sufficient quality to be profitably used for subsequent applications aimed at uncovering new biomedical knowledge. Although proximity filtering is only marginally effective for enhancing the precision of relations extracted with co-occurrence processing, it is likely to benefit methods based, even partially, on syntactic structure, regardless of the relation. C1 Politecn Milan, Dept Bioengn, I-20133 Milan, Italy. Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. RP Masseroli, M (reprint author), Politecn Milan, Dept Bioengn, I-20133 Milan, Italy. EM masseroli@biomed.polimi.it; halil@nlm.nih.gov; flang@mail.nih.gov; tcr@nlm.nih.gov FU Intramural NIH HHS NR 43 TC 17 Z9 17 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 8 PY 2006 VL 7 AR 291 DI 10.1186/1471-2105-7-291 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 086OG UT WOS:000240682300001 PM 16762065 ER PT J AU Zotenko, E O'Leary, DP Przytycka, TM AF Zotenko, Elena O'Leary, Dianne P. Przytycka, Teresa M. TI Secondary structure spatial conformation footprint: a novel method for fast protein structure comparison and classification SO BMC STRUCTURAL BIOLOGY LA English DT Article ID STRUCTURE ALIGNMENT; DATA-BANK; RECOGNITION; SIMILARITY; TOPOLOGY; SCOP AB Background: Recently a new class of methods for fast protein structure comparison has emerged. We call the methods in this class projection methods as they rely on a mapping of protein structure into a high-dimensional vector space. Once the mapping is done, the structure comparison is reduced to distance computation between corresponding vectors. As structural similarity is approximated by distance between projections, the success of any projection method depends on how well its mapping function is able to capture the salient features of protein structure. There is no agreement on what constitutes a good projection technique and the three currently known projection methods utilize very different approaches to the mapping construction, both in terms of what structural elements are included and how this information is integrated to produce a vector representation. Results: In this paper we propose a novel projection method that uses secondary structure information to produce the mapping. First, a diverse set of spatial arrangements of triplets of secondary structure elements, a set of structural models, is automatically selected. Then, each protein structure is mapped into a high-dimensional vector of "counts" or footprint, where each count corresponds to the number of times a given structural model is observed in the structure, weighted by the precision with which the model is reproduced. We perform the first comprehensive evaluation of our method together with all other currently known projection methods. Conclusion: The results of our evaluation suggest that the type of structural information used by a projection method affects the ability of the method to detect structural similarity. In particular, our method that uses the spatial conformations of triplets of secondary structure elements outperforms other methods in most of the tests. C1 Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. Univ Maryland, Inst Adv Comp Studies, College Pk, MD 20742 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Przytycka, TM (reprint author), Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. EM przytyck@mail.nih.gov OI Zotenko, Elena/0000-0002-0256-3195 FU Intramural NIH HHS NR 26 TC 13 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD JUN 8 PY 2006 VL 6 AR 12 DI 10.1186/1472-6807-6-12 PG 12 WC Biophysics SC Biophysics GA 069QJ UT WOS:000239463000001 PM 16762072 ER PT J AU Feitosa, FM Calvo, E Merino, EF Durham, AM James, AA de Bianchi, AG Marinotti, O Capurro, ML AF Feitosa, Fabiana M. Calvo, Eric Merino, Emilio F. Durham, Alan M. James, Anthony A. de Bianchi, Antonio G. Marinotti, Osvaldo Capurro, Margareth L. TI A transcriptome analysis of the Aedes aegypti vitellogenic fat body SO JOURNAL OF INSECT SCIENCE LA English DT Article ID MOSQUITO ANOPHELES-GAMBIAE; DROSOPHILA-MELANOGASTER; BLOOD MEAL; BINDING-PROTEINS; GENOME SEQUENCE; MALARIA; GENE; GENERATION; FAMILIES; DATABASE AB Aedes (Stegonryia) aegypti is an important dengue vector in tropical and subtropical zones throughout the world. A transcriptome of Ae. aegypti vitellogenic fat bodies is described here. The fat body is a dynamic tissue that participates in multiple biochemical functions of intermediate metabolism. A total Of 589 randomly selected eDNAs were assembled into 262 clusters based on their primary sequence similarities. The putative translated proteins were classified into categories based on their function in accordance with significant similarity using the BlastX at NCBI FFP site and Pfam (Bateman et al. 2000) and SMART (Schultz et al. 2000) databases. The characterization of transcripts expressed in the fat body of Ae. aegypti at 24 hours post blood meal provides a basic tool for understanding the processes occurring in this organ and could identify putative new genes whose promoters can be used to specifically express transgenes in the fat bodies of Ae.-aegypti. C1 Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508000 Sao Paulo, SP, Brazil. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Univ Sao Paulo, Inst Math & Stat, Dept Comp Sci, BR-05508000 Sao Paulo, Brazil. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. RP Feitosa, FM (reprint author), Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP, Brazil. EM mcapurro@icb.usp.br RI Capurro, Margareth/F-8679-2012; Durham, Alan/A-8757-2014 OI Capurro, Margareth/0000-0002-7480-2116; NR 32 TC 11 Z9 11 U1 0 U2 10 PU UNIV ARIZONA PI TUCSON PA LIBRARY C327, TUCSON, AZ 85721 USA SN 1536-2442 J9 J INSECT SCI JI J Insect Sci. PD JUN 8 PY 2006 VL 6 AR 06 PG 26 WC Entomology SC Entomology GA 085PY UT WOS:000240617200001 ER PT J AU Joiner, WJ Crocker, A White, BH Sehgal, A AF Joiner, WJ Crocker, A White, BH Sehgal, A TI Sleep in Drosophila is regulated by adult mushroom bodies SO NATURE LA English DT Article ID SHORT-TERM-MEMORY; LOCOMOTOR-ACTIVITY; MELANOGASTER; REST; LOCALIZATION; EXPRESSION; ABLATION AB Sleep is one of the few major whole-organ phenomena for which no function and no underlying mechanism have been conclusively demonstrated. Sleep could result from global changes in the brain during wakefulness or it could be regulated by specific loci that recruit the rest of the brain into the electrical and metabolic states characteristic of sleep. Here we address this issue by exploiting the genetic tractability of the fruitfly, Drosophila melanogaster, which exhibits the hallmarks of vertebrate sleep(1-4). We show that large changes in sleep are achieved by spatial and temporal enhancement of cyclic-AMP-dependent protein kinase ( PKA) activity specifically in the adult mushroom bodies of Drosophila. Other manipulations of the mushroom bodies, such as electrical silencing, increasing excitation or ablation, also alter sleep. These results link sleep regulation to an anatomical locus known to be involved in learning and memory. C1 Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Sehgal, A (reprint author), Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. EM amita@mail.med.upenn.edu FU Intramural NIH HHS; NINDS NIH HHS [R01 NS072431] NR 30 TC 196 Z9 199 U1 4 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 8 PY 2006 VL 441 IS 7094 BP 757 EP 760 DI 10.1038/nature04811 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 050NL UT WOS:000238095100056 PM 16760980 ER PT J AU Dave, SS Fu, K Wright, GW Lam, LT Kluin, P Boerma, EJ Greiner, TC Weisenburger, DD Rosenwald, A Ott, G Muller-Hermelink, H Gascoyne, RD Delabie, J Rimsza, LM Braziel, RM Grogan, TM Campo, E Jaffe, ES Dave, BJ Sanger, W Bast, M Vose, JM Armitage, JO Connors, JM Smeland, EB Kvaloy, S Holte, H Fisher, RI Miller, TP Montserrat, E Wilson, WH Bahl, M Zhao, H Yang, LM Powell, J Simon, R Chan, WC Staudt, LM AF Dave, SS Fu, K Wright, GW Lam, LT Kluin, P Boerma, EJ Greiner, TC Weisenburger, DD Rosenwald, A Ott, G Muller-Hermelink, H Gascoyne, RD Delabie, J Rimsza, LM Braziel, RM Grogan, TM Campo, E Jaffe, ES Dave, BJ Sanger, W Bast, M Vose, JM Armitage, JO Connors, JM Smeland, EB Kvaloy, S Holte, H Fisher, RI Miller, TP Montserrat, E Wilson, WH Bahl, M Zhao, H Yang, LM Powell, J Simon, R Chan, WC Staudt, LM CA Lymphoma Leukemia Molecular Profil TI Molecular diagnosis of Burkitt's lymphoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; GENE-EXPRESSION; ADULTS; CHEMOTHERAPY; EXPERIENCE; SUBGROUPS; PATTERNS; SURVIVAL; REGIMENS AB Background: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma. Methods: Tumor-biopsy specimens from 303 patients with aggressive lymphomas were profiled for gene expression and were also classified according to morphology, immunohistochemistry, and detection of the t(8;14) c-myc translocation. Results: A classifier based on gene expression correctly identified all 25 pathologically verified cases of classic Burkitt's lymphoma. Burkitt's lymphoma was readily distinguished from diffuse large-B-cell lymphoma by the high level of expression of c-myc target genes, the expression of a subgroup of germinal-center B-cell genes, and the low level of expression of major-histocompatibility-complex class I genes and nuclear factor-kappa B target genes. Eight specimens with a pathological diagnosis of diffuse large-B-cell lymphoma had the typical gene-expression profile of Burkitt's lymphoma, suggesting they represent cases of Burkitt's lymphoma that are difficult to diagnose by current methods. Among 28 of the patients with a molecular diagnosis of Burkitt's lymphoma, the overall survival was superior among those who had received intensive chemotherapy regimens instead of lower-dose regimens. Conclusions: Gene-expression profiling is an accurate, quantitative method for distinguishing Burkitt's lymphoma from diffuse large-B-cell lymphoma. C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Groningen, Med Ctr, Groningen, Netherlands. Univ Wurzburg, Wurzburg, Germany. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Norwegian Radium Hosp, Norway Hosp Clin, Oslo, Norway. SW Oncol Grp, Seattle, WA USA. Univ Arizona, Ctr Canc, Tucson, AZ USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Barcelona, Barcelona, Spain. Univ Oslo, Oslo, Norway. Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY USA. RP Staudt, LM (reprint author), NCI, Metab Branch, CCR, NIH, Bldg 10,Rm 4N114,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU Intramural NIH HHS; NCI NIH HHS [UO1-CA84967] NR 33 TC 432 Z9 460 U1 4 U2 17 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 JUN 8 PY 2006 VL 354 IS 23 BP 2431 EP 2442 DI 10.1056/NEJMoa055759 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 050PQ UT WOS:000238100800005 PM 16760443 ER PT J AU Fok, SYY Rubin, JS Pixley, F Condeelis, J Braet, F Soon, LL AF Fok, Sandra Y. Y. Rubin, Jeffrey S. Pixley, Fiona Condeelis, John Braet, Filip Soon, Lilian L. TI Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study SO BMC CANCER LA English DT Article ID ACTIN POLYMERIZATION; GENE-EXPRESSION; MOTILITY; PROTEIN; RECEPTORS; DIVERSITY; ADENOCARCINOMA; HETEROGENEITY; CYTOSKELETON; METASTASIS AB Background: Non-small cell lung cancer is the most common cause of early casualty from malignant disease in western countries. The heterogeneous nature of these cells has been identified by histochemical and microarray biomarker analyses. Unfortunately, the morphological, molecular and biological variation within cell lines used as models for invasion and metastasis are not well understood. In this study, we test the hypothesis that heterogeneous cancer cells exhibit variable motility responses such as chemokinesis and chemotaxis that can be characterized molecularly. Methods: A subpopulation of H460 lung cancer cells called KINE that migrated under chemokinetic ( no gradient) conditions was harvested from Boyden chambers and cultured. Time-lapsed microscopy, immunofluorescence microscopy and microarray analyses were then carried out comparing chemokinetic KINE cells with the unselected CON cell population. Results: Time-lapsed microscopy and analysis showed that KINE cells moved faster but less directionally than the unselected control population ( CON), confirming their chemokinetic character. Of note was that chemokinetic KINE cells also chemotaxed efficiently. KINE cells were less adhesive to substrate than CON cells and demonstrated loss of mature focal adhesions at the leading edge and the presence of non-focalized cortical actin. These characteristics are common in highly motile amoeboid cells that may favour faster motility speeds. KINE cells were also significantly more invasive compared to CON. Gene array studies and real-time PCR showed the downregulation of a gene called, ROM, in highly chemokinetic KINE compared to mainly chemotactic CON cells. ROM was also reduced in expression in a panel of lung cancer cell lines compared to normal lung cells. Conclusion: This study shows that cancer cells that are efficient in both chemokinesis and chemotaxis demonstrate high invasion levels. These cells possess different morphological, cytoskeletal and adhesive properties from another population that are only efficient at chemotaxis, indicating a loss in polarity. Understanding the regulation of polarity in the context of cell motility is important in order to improve control and inhibition of invasion and metastasis. C1 Univ Sydney, Australian Key Ctr Microscopy & Microanal, Electron Microscope Unit, Sydney, NSW 2006, Australia. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. RP Soon, LL (reprint author), Univ Sydney, Australian Key Ctr Microscopy & Microanal, Electron Microscope Unit, Sydney, NSW 2006, Australia. EM sfok5959@mail.usyd.edu.au; rubinj@mail.nih.gov; pixley@aecom.yu.edu; condeeli@aecom.yu.edu; filip.braet@emu.usyd.edu.au; lilian.soon@emu.usyd.edu.au NR 35 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUN 7 PY 2006 VL 6 AR 151 DI 10.1186/1471-2407-6-151 PG 12 WC Oncology SC Oncology GA 062YJ UT WOS:000238982600001 ER PT J AU Huang, FL Huang, KP Wu, JF Boucheron, C AF Huang, FL Huang, KP Wu, JF Boucheron, C TI Environmental enrichment enhances neurogranin expression and hippocampal learning and memory but fails to rescue the impairments of neurogranin null mutant mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurogranin; environmental enrichment; Ca2+/calmodulin; learning and memory; synaptic plasticity; hippocampus ID LONG-TERM POTENTIATION; PROTEIN-KINASE-II; SYNAPTIC PLASTICITY; SPATIAL MEMORY; MOUSE MODEL; DEFICITS; MECHANISM; NEURONS; DISEASE AB Environmental enrichment is known to enhance hippocampal neurogenesis and cognitive functions. Neurogranin (Ng), a specific substrate of protein kinase C(PKC), is abundantly expressed in brain regions important for cognitive functions. Deletion of Ng in mice causes severe deficits in spatial learning and long-term potentiation (LTP) in the hippocampal CA1 region. These Ng-/- mice, as compared with Ng(+/+), respond poorly after treatment of their hippocampal slices with agents that activate signaling molecules important for learning and memory, including Ca2+/calmodulin-dependent protein kinase II (alpha CaMKII), PKC, protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein ( CREB). In the present study, adult mice were housed in either regular home cages ( control group) or more spacious cages with an exercise wheel and change of toys twice per week ( enriched group) for at least 3 weeks. Enriched Ng+/+ and Ng+/- mice showed enhanced LTP in the hippocampal CA1 after high-frequency stimulation, but Ng-/- mice were affected only minimally. Behaviorally, the enriched Ng+/- and Ng+/-, but not Ng-/- mice, performed significantly better than their respective control cohorts in Morris water maze and in step-down fear conditioning. Enriched Ng-/- mice also showed improvement in the radial arm maze. Quantitative immunoblot analyses showed that the enriched groups of all three genotypes exhibited elevated hippocampal levels of alpha CaMKII and CREB, but not ERK. Interestingly, enrichment caused a significant increase in hippocampal Ng levels both in Ng+/+ and Ng+/- mice that seemed to contribute to their improved LTP and behavioral performances. These results suggest that Ng gates the neuronal signaling reactions involved in learning and memory. During environmental enrichment, these Ng-regulated reactions are also critical for the enhancement of synaptic plasticity and cognitive functions. C1 NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Huang, FL (reprint author), NICHHD, Metab Regulat Sect, Endocrinol & Reprod Res Branch, NIH, 49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM fhuang@mail.nih.gov FU Intramural NIH HHS NR 22 TC 69 Z9 75 U1 0 U2 6 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 JUN 7 PY 2006 VL 26 IS 23 BP 6230 EP 6237 DI 10.1523/JNEUROSCI.1182-06.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 051QC UT WOS:000238174600013 PM 16763030 ER PT J AU Grati, M Schneider, ME Lipkow, K Strehler, EE Wenthold, RJ Kachar, B AF Grati, M Schneider, ME Lipkow, K Strehler, EE Wenthold, RJ Kachar, B TI Rapid turnover of stereocilia membrane proteins: Evidence from the trafficking and mobility of plasma membrane Ca2+-ATPase SO JOURNAL OF NEUROSCIENCE LA English DT Article DE PMCA2; hair cells; endocytosis; hearing; membrane protein mobility; stereocilia ID HAIR-CELL STEREOCILIA; INDUCED HEARING-LOSS; CUTICULAR PLATE; MOLECULAR TREADMILL; TIP LINKS; MICE; CA2+; TRANSDUCTION; RESOLUTION; COMPLEXES AB We studied the spatial distribution, mobility, and trafficking of plasma membrane Ca2+ ATPase-2 ( PMCA2), a protein enriched in the hair cell apical membrane and essential for hair cell function. Using immunofluorescence, we determined that PMCA2 is enriched in the stereocilia and present at a relatively low concentration in the kinocilium and in the remaining apical membrane. Using an antibody to the extracellular domain of PMCA2 as a probe, we observed that PMCA2 diffuses laterally from the stereocilia membrane and is internalized at the apical cell border maintaining an estimated half-life of residency in the stereocilia of similar to 5 - 7 h. A computer simulation of our data indicates that PMCA2 has an estimated global diffusion coefficient of 0.01 - 0.005 mu m(2)/s. Using a green fluorescent protein tag, we observed that PMCA2 is rapidly delivered to the apical cell border from where it diffuses to the entire stereocilia surface. Fluorescence recovery after photobleaching experiments show that similar to 60% of PMCA2 in the stereocilia exhibit high mobility with a diffusion coefficient of 0.1 - 0.2 mu m(2)/s, whereas the remaining pool represents a relatively immobile fraction. These results suggest that PMCA2 molecules maintain transient interactions with other components of the stereocilia, and the mobile pool of PMCA2 mediates the exchange between the stereocilia and the removal and delivery sites at the periphery of the apical cell surface. This rapid turnover of a major stereocilia membrane protein matches the previously described rapid turnover of proteins of the stereocilia actin core, further demonstrating that these organelles undergo rapid continuous renewal. C1 Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3DY, England. Mayo Clin, Coll Med, Rochester, MN 55905 USA. RP Kachar, B (reprint author), Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, 50 S Dr,Room 4249, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov RI Grati, M'hamed/C-9563-2011 FU Intramural NIH HHS; NIGMS NIH HHS [GM28835, R01 GM028835-24, R01 GM064713, R01 GM028835-25, R01 GM028835, GM64713] NR 34 TC 34 Z9 35 U1 0 U2 2 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 JUN 7 PY 2006 VL 26 IS 23 BP 6386 EP 6395 DI 10.1523/JNEUROSCI.1215-06.2006 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 051QC UT WOS:000238174600030 PM 16763047 ER PT J AU Narazaki, M Tosato, G AF Narazaki, M Tosato, G TI Conflicting results from clinical observations and murine models: What is the role of plasminogen activators in tumor growth? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MATRIX-METALLOPROTEINASE INHIBITORS; BREAST-CANCER PATIENTS; BASEMENT-MEMBRANE; UROKINASE; PROGRESSION; METASTASIS; THERAPY; MICROENVIRONMENT; ANGIOGENESIS; PROTEASES C1 NCI, Basic Res Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Basic Res Lab, Canc Res Ctr, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov OI narazaki, masashi/0000-0002-5613-4409 NR 28 TC 1 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 7 PY 2006 VL 98 IS 11 BP 726 EP 727 DI 10.1093/jnci/djj227 PG 2 WC Oncology SC Oncology GA 054PE UT WOS:000238390300002 PM 16757692 ER PT J AU Marcus, PM Bergstralh, EJ Zweig, MH Harris, A Offord, KP Fontana, RS AF Marcus, PM Bergstralh, EJ Zweig, MH Harris, A Offord, KP Fontana, RS TI Extended lung cancer incidence follow-up in the Mayo Lung Project and overdiagnosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DETECTION PROGRAM; CARCINOMA; MORTALITY; PREVALENCE; FREQUENCY; IMPACT; CHEST AB Background. A troubling aspect of cancer screening is the potential for overdiagnosis, i.e., detection of disease that, in the absence of screening, would never have been diagnosed. Overdiagnosis is of particular concern in lung cancer screening because newer screening modalities can identify small nodules of unknown clinical significance. Previously published analyses of data from the Mayo Lung Project, a large randomized controlled trial conducted among 9211 male cigarette smokers in the 1970s and early 1980s indicated that overdiagnosis might exist in lung cancer screening. At the end of follow-up (July 1, 1983), no difference in lung cancer mortality was observed, but an excess of 46 cases in the intervention arm suggested overdiagnosis. Because that excess could instead have resulted from short follow-up time, we investigated this possibility by conducting long-term lung cancer incidence follow-up. Methods: We investigated the lung cancer status through 1999 of the 7118 participants in the Mayo Lung Project who were alive and without diagnosed lung cancer in 1983 by use of medical records, surveys mailed to participants or next-of-kin, and state death certificates. Results: Information was available for 6101 participants, including 811 with inconclusive lung cancer status. From November 1971 through December 31, 1999, 585 participants in the intervention arm and 500 in the usual-care arm were diagnosed with lung cancer. Conclusions: The persistence of excess cases in the intervention arm after 16 additional years of follow-up provides continued support for overdiagnosis in lung cancer screening. C1 NCI, Div Canc Prevent, Biometry Res Grp, US Dept HSSS,NIH, Bethesda, MD 20895 USA. Mayo Clin & Mayo Fdn, Div Biostat, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Survey Res Ctr, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. RP Marcus, PM (reprint author), NCI, Div Canc Prevent, Biometry Res Grp, US Dept HSSS,NIH, 6130 Execut Blvd,Suite 3131, Bethesda, MD 20895 USA. EM pm145q@nih.gov NR 34 TC 121 Z9 124 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 7 PY 2006 VL 98 IS 11 BP 748 EP 756 DI 10.1093/jnci/djj207 PG 9 WC Oncology SC Oncology GA 054PE UT WOS:000238390300010 PM 16757699 ER PT J AU Han, SS Peng, LP Chung, ST DuBois, W Maeng, SH Shaffer, AL Sporn, MB Janz, S AF Han, Seong-Su Peng, Liangping Chung, Seung-Tae DuBois, Wendy Maeng, Sung-Ho Shaffer, Arthur L. Sporn, Michael B. Janz, Siegfried TI CDDO-imidazolide inhibits growth and survival of c-Myc-induced mouse B cell and plasma cell neoplasms SO MOLECULAR CANCER LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; MULTIPLE-MYELOMA CELLS; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; OXIDATIVE STRESS; GENE-EXPRESSION; CDNA MICROARRAY; LEUKEMIA-CELLS; UP-REGULATION; CANCER CELLS AB Background: Gene-targeted iMyc(E mu) mice that carry a His(6)-tagged mouse Myc(c-myc) cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, E mu, are prone to B cell and plasma cell neoplasms, such as lymphoblastic B-cell lymphoma (LBL) and plasmacytoma (PCT). Cell lines derived from Myc-induced neoplasms of this sort may provide a good model system for the design and testing of new approaches to prevent and treat MYC-driven B cell and plasma cell neoplasms in human beings. To test this hypothesis, we used the LBL-derived cell line, iMyc(E mu)-1, and the newly established PCT-derived cell line, iMyc(E mu)-2, to evaluate the growth inhibitory and death inducing potency of the cancer drug candidate, CDDO-imidazolide (CDDO-Im). Methods: Morphological features and surface marker expression of iMyc(E mu)-2 cells were evaluated using cytological methods and FACS, respectively. mRNA expression levels of the inserted Myc(His) and normal Myc genes were determined by allele-specific RT-PCR and qPCR. Myc protein was detected by immunoblotting. Cell cycle progression and apoptosis were analyzed by FACS. The expression of 384 "pathway" genes was assessed with the help of Superarray((c)) cDNA macroarrays and verified, in part, by RT-PCR. Results: Sub-micromolar concentrations of CDDO-Im caused growth arrest and apoptosis in iMyc(E mu)-1 and iMyc(E mu)-2 cells. CDDO-Im-dependent growth inhibition and apoptosis were associated in both cell lines with the up-regulation of 30 genes involved in apoptosis, cell cycling, NF kappa B signaling, and stress and toxicity responses. Strongly induced (>= 10 fold) were genes encoding caspase 14, heme oxygenase 1 (Hmox1), flavin-containing monooxygenase 4 (Fmo4), and three members of the cytochrome P450 subfamily 2 of mixed-function oxygenases (Cyp2a4, Cyp2b9, Cyp2c29). CDDO-Im-dependent gene induction coincided with a decrease in Myc protein. Conclusion: Growth arrest and killing of neoplastic mouse B cells and plasma cells by CDDO-Im, a closely related derivative of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid, appears to be caused, in part, by drug-induced stress responses and reduction of Myc. C1 NCI, Genet Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, CCR, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol, Hanover, NH 03756 USA. Univ Kentucky, Dept Radiat Med, Markey Canc Ctr, Lexington, KY 40536 USA. RP Janz, S (reprint author), NCI, Genet Lab, CCR, NIH, Bldg 37, Bethesda, MD 20892 USA. EM hanse@mail.nih.gov; lp232@georgetown.edu; chungs@mail.nih.gov; duboisw@dino.nci.nih.gov; true_vj@hotmail.com; as275s@nih.gov; Michael.B.Sporn@Dartmouth.EDU; sj4s@nih.gov FU Intramural NIH HHS NR 52 TC 10 Z9 10 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD JUN 7 PY 2006 VL 5 AR 22 DI 10.1186/1476-4598-5-22 PG 15 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 076PB UT WOS:000239969100001 PM 16759389 ER PT J AU Roux, AVD Ranjit, N Powell, L Jackson, S Lewis, TT Shea, S Wu, C AF Roux, Ana V. Diez Ranjit, Nalini Powell, Lynda Jackson, Sharon Lewis, Tene T. Shea, Steven Wu, Colin TI Psychosocial factors and coronary calcium in adults without clinical cardiovascular disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; HEART-RATE-VARIABILITY; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; MAJOR DEPRESSION; YOUNG-ADULTS; CAROTID ATHEROSCLEROSIS; PSYCHOLOGICAL-FACTORS; PLATELET REACTIVITY; TRAIT ANXIETY AB Background: Psychosocial factors have been linked to coronary events, but the mechanisms underlying these associations have not been established. Evidence is mixed regarding associations of psychosocial factors with subclinical coronary atherosclerosis. Objective: To examine associations of 4 psychosocial factors (depressive symptoms, anger, anxiety, and chronic stress) with the presence of subclinical coronary atherosclerosis. Design: Cross-sectional study. Setting: The Multiethnic Study of Atherosclerosis, a population-based study of subclinical atherosclerosis. Patients: A multiethnic sample of 6789 adults, 45 to 84 years of age, with no history of clinical cardiovascular disease. Measurements: Coronary calcium was assessed by using chest computed tomography, and psychosocial factors were assessed by using questionnaires with validated scales. Results: There was no evidence that higher levels of the psychosocial measures were associated with greater prevalence of calcification or with greater amounts of calcium among persons with calcium. Age- and risk factor-adjusted relative prevalences of coronary calcification in men for the top fourth category versus the bottom fourth category of anger, anxiety, and depressive symptoms were 0.94 (95% Cl, 0.88 to 1.01), 0.97 (Cl, 0.90 to 1.04), and 0.97 (Cl, 0.90 to 1.05), respectively; these values for women were 1.01 (Cl, 0.90 to 1.15), 0.93 (Cl, 0.83 to 1.05), and 0.92 (Cl, 0.82 to 1.04), respectively. Relative prevalences for the top versus the bottom category of chronic stress burden were 1.02 (Cl, 0.94 to 1.11) for men and 0.88 (Cl, 0.79 to 0.99) for women. Limitations: Current measures of psychosocial factors may be a poor proxy for cumulative exposure during development of atherosclerosis. Conclusion: Depressive symptoms, anger, anxiety, and chronic stress burden were not associated with coronary calcification in a multiethnic sample of asymptomatic adults. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48103 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Columbia Univ, New York, NY USA. NIH, Bethesda, MD 20892 USA. RP Roux, AVD (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 1214 S Univ,2nd Floor, Ann Arbor, MI 48103 USA. EM adiezrou@umich.edu NR 73 TC 48 Z9 48 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 6 PY 2006 VL 144 IS 11 BP 822 EP 831 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 049ZN UT WOS:000238057000005 ER PT J AU Bell, SP Curran, PK Choi, S Mindell, JA AF Bell, SP Curran, PK Choi, S Mindell, JA TI Site-directed fluorescence studies of a prokaryotic ClC antiporter SO BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL-CHANGES; CHLORIDE CHANNEL; SELECTIVITY FILTER; INHIBITOR; GLUTAMATE; HOMOLOG; PORE AB Channels and transporters of the ClC family serve a variety of physiological functions. Understanding of their gating and transport mechanisms remains incomplete, with disagreement over the extent of protein conformational change involved. Using site-directed fluorescence labeling, we probe ClC-ec1, a prokaryotic ClC, for transport-related structural rearrangements. We specifically label cysteines introduced at several positions in the R helix of ClC-ec1 with AlexaFluor 488, an environment-sensitive fluorophore, and demonstrate that the labeled mutants show H+/Cl- transport activity indistinguishable from that of the wild-type protein. At each position that we examined we observe fluorescence changes upon acidification over the same pH range that is known to activate transport. The fluorescence change is also sensitive to Cl- concentration; furthermore, the Cl- and H+ dependencies are coupled as would be expected if the fluorescence change reflected a conformational change required for transport. Together, the results suggest that the changes in fluorescence report protein conformational changes underlying the transport process. Labeled transporters mutated to remove a glutamate critical to proton-coupled chloride transport retain pH-dependent fluorescence changes, suggesting that multiple residues confer pH dependence on the transport mechanism. These results have implications for models of transport and gating in ClC channels and transporters. C1 NINDS, MTBU, Porter Neurosci Ctr, NIH, Bethesda, MD 20892 USA. RP Mindell, JA (reprint author), NINDS, MTBU, Porter Neurosci Ctr, NIH, 35 Convent Dr,Bldg 35,MSC 3701, Bethesda, MD 20892 USA. EM mindellj@ninds.nih.gov OI Mindell, Joseph/0000-0002-6952-8247 FU Intramural NIH HHS NR 24 TC 24 Z9 25 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 6 PY 2006 VL 45 IS 22 BP 6773 EP 6782 DI 10.1021/bi0523815 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048AV UT WOS:000237920900002 PM 16734414 ER PT J AU Golovko, MY Rosenberger, TA Faergeman, NJ Feddersen, S Cole, NB Pribill, I Berger, J Nussbaum, RL Murphy, EJ AF Golovko, Mikhail Y. Rosenberger, Thad A. Faergeman, Nils J. Feddersen, Slren Cole, Nelson B. Pribill, Ingrid Berger, Johannes Nussbaum, Robert L. Murphy, Eric J. TI Acyl-CoA synthetase activity links wild-type but not mutant alpha-synuclein to brain arachidonate metabolism SO BIOCHEMISTRY LA English DT Article ID ACID-BINDING PROTEIN; POLYUNSATURATED FATTY-ACIDS; GENE-ABLATED MICE; LONG-TERM POTENTIATION; LEWY BODY DEMENTIA; A-BETA COMPONENT; PARKINSONS-DISEASE; RAT-BRAIN; SUBCELLULAR-LOCALIZATION; ALZHEIMERS-DISEASE AB Because alpha-synuclein (Snca) has a role in brain lipid metabolism, we determined the impact that the loss of alpha-synuclein had on brain arachidonic acid (20:4n-6) metabolism in vivo using Snca(-/-) mice. We measured [1-C-14]20:4n-6 incorporation and turnover kinetics in brain phospholipids using an established steady-state kinetic model. Liver was used as a negative control, and no changes were observed between groups. In Snca-/- brains, there was a marked reduction in 20:4n-6-CoA mass and in microsomal acyl-CoA synthetase (Acsl) activity toward 20: 4n-6. Microsomal Acsl activity was completely restored after the addition of exogenous wild-type mouse or human alpha-synuclein, but not by A30P, E46K, and A53T forms of alpha-synuclein. Acsl and acyl-CoA hydrolase expression was not different between groups. The incorporation and turnover of 20: 4n-6 into brain phospholipid pools were markedly reduced. The dilution coefficient I, which indicates 20:4n-6 recycling between the acyl-CoA pool and brain phospholipids, was increased 3.3-fold, indicating more 20:4n-6 was entering the 20:4n-6-CoA pool from the plasma relative to that being recycled from the phospholipids. This is consistent with the reduction in Acsl activity observed in the Snca-/- mice. Using titration microcalorimetry, we determined that alpha-synuclein bound free 20:4n-6 (K-d = 3.7 mu M) but did not bind 20:4n-6-CoA. These data suggest alpha-synuclein is involved in substrate presentation to Acsl rather than product removal. In summary, our data demonstrate that alpha-synuclein has a major role in brain 20:4n-6 metabolism through its modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity, although mutant forms of alpha-synuclein fail to restore this activity. C1 Univ N Dakota, Dept Pharmacol, Sch Med & Hlth Sci, Grand Forks, ND 58202 USA. Univ N Dakota, Dept Chem, Grand Forks, ND 58202 USA. Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Vienna, Div Neuroimmunol, Ctr Brain Res Inst, A-1090 Vienna, Austria. RP Murphy, EJ (reprint author), Univ N Dakota, Dept Pharmacol, Sch Med & Hlth Sci, 501 N Columbia Rd, Grand Forks, ND 58202 USA. EM emurphy@medicine.nodak.edu RI Berger, Johannes/A-9122-2014 OI Berger, Johannes/0000-0003-0182-2658 FU Intramural NIH HHS; NCRR NIH HHS [1P20 RR17699-01, P20 RR017699, P20 RR017699-010004]; NINDS NIH HHS [NS043697-01A, R21 NS043697, R21 NS043697-02] NR 94 TC 45 Z9 46 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 6 PY 2006 VL 45 IS 22 BP 6956 EP 6966 DI 10.1021/bi0600289 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048AV UT WOS:000237920900019 PM 16734431 ER PT J AU Kavey, REW AF Kavey, REW TI Optimal management strategies for patients with complex congenital heart disease SO CIRCULATION LA English DT Editorial Material ID STENT IMPLANTATION; RISK-FACTORS; PULMONARY ATRESIA; SURGICAL REPAIR; FOLLOW-UP; TETRALOGY; FALLOT; CONDUIT; MULTICENTER; OBSTRUCTION C1 NHLBI, Bethesda, MD 20892 USA. RP Kavey, REW (reprint author), NHLBI, Bldg 31,Suite 4A10, Bethesda, MD 20892 USA. EM kaveyr@nhlbi.nih.gov NR 20 TC 0 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 6 PY 2006 VL 113 IS 22 BP 2569 EP 2571 DI 10.1161/CIRCULATIONAHA.106.629154 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 049RE UT WOS:000238033400005 PM 16754811 ER PT J AU Dawid, I AF Dawid, I TI Q & A - Igor David SO CURRENT BIOLOGY LA English DT Editorial Material C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, I (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 6 PY 2006 VL 16 IS 11 BP R391 EP R392 DI 10.1016/j.cub.2006.05.016 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 052PP UT WOS:000238245900003 PM 16791937 ER PT J AU Saghert, D Brunell, D Hejtmancik, JF Kantorow, M Brot, N Weissbach, H AF Saghert, Daphna Brunell, David Hejtmancik, J. Fielding Kantorow, Marc Brot, Nathan Weissbach, Herbert TI Thionein can serve as a reducing agent for the methionine sulfoxide reductases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE metallothioneins; reducing systems ID ESCHERICHIA-COLI; OXIDATIVE STRESS; CATALYTIC MECHANISM; OXIDIZED PROTEINS; A MSRA; METALLOTHIONEIN; REDUCTION; GENE; IDENTIFICATION; LOCALIZATION AB It has been generally accepted, primarily from studies on methionine sulfoxide reductase (Msr) A, that the biological reducing agent for the members of the Msr family is reduced thioredoxin (Trx), although high levels of DTT can be used as the reductant in vitro. Preliminary experiments using both human recombinant MsrB2 (hMsrB2) and MsrB3 (hMsrB3) showed that although DTT can function in vitro as the reducing agent, Trx works very poorly, prompting a more careful comparison of the ability of DTT and Trx to function as reducing agents with the various members of the Msr family. Escherichia coli MsrA and MsrB and bovine MsrA efficiently use either Trx or DTT as reducing agents. In contrast, hMsrB2 and hMsrB3 show < 10% of the activity with Trx as compared with DTT, raising the possibility that, in animal cells, Trx may not be the direct hydrogen donor or that there may be a Trx-independent reducing system required for MsrB2 and MsrB3 activity. A heat-stable protein has been detected in bovine liver that, in the presence of EDTA, can support the Msr reaction in the absence of either Trx or DTT. This protein has been identified as a zinc-containing metallothionein (Zn-MT). The results indicate that thionein (T), which is formed when the zinc is removed from Zn-MT, can function as a reducing system for the Msr proteins because of its high content of cysteine residues and that Trx can reduce oxidized T. C1 Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, Boca Raton, FL 33431 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Hosp Special Surg, Med Ctr, Dept Microbiol & Immunol, New York, NY 10021 USA. RP Weissbach, H (reprint author), Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, 777 Glades Rd, Boca Raton, FL 33431 USA. EM hweissba@fau.edu FU NEI NIH HHS [EY13022MK, R01 EY013022-07, R01 EY013022] NR 40 TC 56 Z9 60 U1 0 U2 4 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 JUN 6 PY 2006 VL 103 IS 23 BP 8656 EP 8661 DI 10.1073/pnas.0602826103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400016 PM 16735467 ER PT J AU Shumaker, DK Dechat, T Kohlmaier, A Adam, SA Bozovsky, MR Erdos, MR Eriksson, M Goldman, AE Khuon, S Collins, FS Jenuwein, T Goldman, RD AF Shumaker, Dale K. Dechat, Thomas Kohlmaier, Alexander Adam, Stephen A. Bozovsky, Matthew R. Erdos, Michael R. Eriksson, Maria Goldman, Anne E. Khuon, Satya Collins, Francis S. Jenuwein, Thomas Goldman, Robert D. TI Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE histone methylation; heterochromatin; progeria ID HUTCHINSON-GILFORD-PROGERIA; X INACTIVATION; METHYLATION; CHROMATIN; HETEROCHROMATIN; TRIMETHYLATION; FARNESYLATION; TRANSCRIPTION; ARCHITECTURE; PROTEINS AB The premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a mutant lamin A (LA Delta 50). Nuclei in cells expressing LA Delta 50 are abnormally shaped and display a loss of heterochromatin. To determine the mechanisms responsible for the loss of heterochromatin, epigenetic marks regulating either facultative or constitutive heterochromatin were examined. In cells from a female HGPS patient, histone H3 trimethylated on lysine 27 (H3K27me3), a mark for facultative heterochromatin, is lost on the inactive X chromosome (Xi). The methyltransferase responsible for this mark, EZH2, is also down-regulated. These alterations are detectable before the changes in nuclear shape that are considered to be the pathological hallmarks of HGPS cells. The results also show a down-regulation of the pericentric constitutive heterochromatin mark, histone H3 trimethylated on lysine 9, and an altered association of this mark with heterochromatin protein 1 alpha (Hp1 alpha) and the CREST antigen. This loss of constitutive heterochromatin is accompanied by an up-regulation of pericentric satellite III repeat transcripts. In contrast to these decreases in histone H3 methylation states, there is an increase in the trimethylation of histone H4K20, an epigenetic mark for constitutive heterochromatin. Expression of LA Delta 50 in normal cells induces changes in histone methylation patterns similar to those seen in HGPS cells. The epigenetic changes described most likely represent molecular mechanisms responsible for the rapid progression of premature aging in HGPS patients. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. Res Inst Mol Pathol, A-1030 Vienna, Austria. Karolinska Inst, Novum, Dept Biosci & Nutr, S-14157 Huddinge, Sweden. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM fc23a@nih.gov; r-goldman@northwestern.edu NR 34 TC 310 Z9 321 U1 6 U2 25 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 JUN 6 PY 2006 VL 103 IS 23 BP 8703 EP 8708 DI 10.1073/pnas.0602569103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400024 PM 16738054 ER PT J AU Bell, JK Askins, J Hall, PR Davies, DR Segal, DM AF Bell, JK Askins, J Hall, PR Davies, DR Segal, DM TI The dsRNA binding site of human toll-like receptor 3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE double-stranded RNA; innate immunity; leucine-rich repeat ID DOUBLE-STRANDED-RNA; HUMAN NK CELLS; DENDRITIC CELLS; PATHOGEN RECOGNITION; MAST-CELLS; ACTIVATION; DOMAIN; MD-2; GLYCOSYLATION; CYTOTOXICITY AB Pathogen recognition by Toll-like receptors (TLRs) initiates innate immune responses that are essential for inhibiting pathogen dissemination and for the development of acquired immunity. The TLRs recognize pathogens with their N-terminal ectodomains (ECD), but the molecular basis for this recognition is not known. Recently we reported the x-ray structure for unliganded TLR3-ECD; however, it has proven difficult to obtain a crystal structure of TLR3 with its ligand, dsRNA. We have now located the TLR3 ligand binding site by mutational analysis. More than 50 single-residue mutations have been generated throughout the TLR3-ECD, but only two, H539E and N541A, resulted in the loss of TLR3 activation and ligand binding functions. These mutations locate the dsRNA binding site on the glycan-free, lateral surface of TLR3 toward the C terminus and suggest a model for dsRNA binding and TLR3 activation. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Davies, DR (reprint author), Bldg 5,Room 338,9000 Rockville Pike, Bethesda, MD 20892 USA. EM david.davies@nih.gov; dave_segal@nih.gov FU Intramural NIH HHS NR 27 TC 133 Z9 144 U1 2 U2 5 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 JUN 6 PY 2006 VL 103 IS 23 BP 8792 EP 8797 DI 10.1073/pnas.0603245103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400039 PM 16720699 ER PT J AU Agrelo, R Cheng, WH Setien, F Ropero, S Espada, J Fraga, MF Herranz, M Paz, MF Sanchez-Cespedes, M Artiga, MJ Guerrero, D Castells, A von Kobbe, C Bohr, VA Esteller, M AF Agrelo, R Cheng, WH Setien, F Ropero, S Espada, J Fraga, MF Herranz, M Paz, MF Sanchez-Cespedes, M Artiga, MJ Guerrero, D Castells, A von Kobbe, C Bohr, VA Esteller, M TI Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA methylation ID PROMOTER HYPERMETHYLATION; SYNDROME PROTEIN; P53-MEDIATED APOPTOSIS; SYNDROME HELICASE; DNA HELICASES; CELL-LINES; EXONUCLEASE; MUTATIONS; LOCALIZATION; ASSOCIATION AB Werner syndrome (WS) is an inherited disorder characterized by premature onset of aging, genomic instability, and increased cancer incidence. The disease is caused by loss of function mutations of the WRN gene, a RecQ family member with both helicase and exonuclease activities. However, despite its putative tumor-suppressor function, little is known about the contribution of WRN to human sporadic malignancies. Here, we report that WRN function is abrogated in human cancer cells by transcriptional silencing associated with CpG island-promoter hypermethylation. We also show that, at the biochemical and cellular levels, the epigenetic inactivation of WRN leads to the loss of WRN-associated exonuclease activity and increased chromosomal instability and apoptosis induced by topoisomerase inhibitors. The described phenotype is reversed by the use of a DNA-demethylating agent or by the reintroduction of WRN into cancer cells displaying methylation-dependent silencing of WRN. Furthermore, the restoration of WRN expression induces tumor-suppressor-like features, such as reduced colony formation density and inhibition of tumor growth in nude mouse xenograft models. Screening a large collection of human primary tumors (n = 630) from different cell types revealed that WRN CpG island hypermethylation was a common event in epithelial and mesenchymal tumorigenesis. Most importantly, WRN hypermethylation in colorectal tumors was a predictor of good clinical response to the camptothecin analogue irinotecan, a topoisomerase inhibitor commonly used in the clinical setting for the treatment of this tumor type. These findings highlight the importance of WRN epigenetic inactivation in human cancer, leading to enhanced chromosomal instability and hypersensitivity to chemotherapeutic drugs. C1 Spanish Natl Canc Ctr, Canc Epigenet Lab, Madrid 28029, Spain. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Ctr Invest Biomed, Serv Navarro Salud, Pamplona 31008, Navarra, Spain. Univ Barcelona, Inst Biomed August Pi & Sunyer, Dept Gastroenterol, Hosp Clin, Barcelona 08036, Spain. RP Esteller, M (reprint author), Spanish Natl Canc Ctr, Canc Epigenet Lab, Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM mesteller@cnio.es RI Sanchez-Cespedes, Montse/H-8485-2012; Esteller, Manel/L-5956-2014; OI Sanchez-Cespedes, Montse/0000-0002-6045-5627; Esteller, Manel/0000-0003-4490-6093; Castells, Antoni/0000-0001-8431-2033 NR 39 TC 143 Z9 151 U1 4 U2 11 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 JUN 6 PY 2006 VL 103 IS 23 BP 8822 EP 8827 DI 10.1073/pnas.0600645103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400044 PM 16723399 ER PT J AU Irarrazabal, CE Burg, MB Ward, SG Ferraris, JD AF Irarrazabal, Carlos E. Burg, Maurice B. Ward, Stephen G. Ferraris, Joan D. TI Phosphatidylinositol 3-kinase mediates activation of ATM by high NaCl and by ionizing radiation: Role in osmoprotective transcriptional regulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA damage; osmotic stress; TonEBP; OREBP ID ENHANCER-BINDING PROTEIN; DNA-DAMAGE; PHOSPHOINOSITIDE 3-KINASE; GROWTH-FACTOR; 85-KILODALTON SUBUNIT; NUCLEAR GTPASE; KIDNEY-CELLS; KINASE-B; STRESS; TONEBP/OREBP AB High NaCl causes DNA double-strand breaks and activates the transcription factor, TonEBP/OREBP, resulting in increased transcription of several protective genes, including those involved in accumulation of compatible organic osmolytes. Several kinases are known to contribute to signaling activation of TonEBP/OREBP, including ATM, which is a member of the phosphatidylinositol 3-kinase (PI3K)-like kinase family and is activated by DNA double-strand breaks. The purpose of the present studies was to investigate a possible role of PI3K Class 1A (PI3K-1A). We found that high NaCl increases PI3K-1A lipid kinase activity. Inhibiting PI3K-1A either by expressing a dominant negative of its regulatory subunit, p85, or by small interfering RNA-mediated knockdown of its catalytic subunit, p110 alpha, reduces high NaCl-induced increases in TonEBP/ OREBP transcriptional activity and transactivation, but not nuclear translocation of TonEBIP/OREBP, or increases in its abundance. Further, suppression of PI3K-1A inhibits the activation of ATM that is caused by either ionizing radiation or high NaCl. High NaCl-induced increase in TonEBP/OREBP activity is reduced equally by inhibition of ATM or PI3K-1A, and the effects are not additive. The conclusions are as follows: (i) PI3K-1A activity is necessary for both high NaCl- and ionizing radiation-induced activation of ATM and (h) high NaCl activates PI3K-1A, which, in turn, contributes to full activation of TonEBP/OREBP via ATM. C1 NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. RP Ferraris, JD (reprint author), NHLBI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM irarrazc@nhibi.nih.gov FU Intramural NIH HHS NR 35 TC 46 Z9 49 U1 0 U2 1 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 JUN 6 PY 2006 VL 103 IS 23 BP 8882 EP 8887 DI 10.1073/pnas.0602911103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400054 PM 16728507 ER PT J AU Rich, BA Vinton, DT Roberson-Nay, R Hommer, RE Berghorst, LH McClure, EB Fromm, SJ Pine, DS Leibenluft, E AF Rich, Brendan A. Vinton, Deborah T. Roberson-Nay, Roxann Hommer, Rebecca E. Berghorst, Lisa H. McClure, Erin B. Fromm, Stephen J. Pine, Daniel S. Leibenluft, Ellen TI Limbic hyperactivation during processing of neutral facial expressions in children with bipolar disorder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amygdala; faces; functional MRI ID SUBCORTICAL BRAIN-REGIONS; TEMPORAL-LOBE STRUCTURES; VOXEL-BASED MORPHOMETRY; AMYGDALA RESPONSE; PSYCHIATRIC-DISORDERS; ANTISOCIAL-BEHAVIOR; EMOTION PERCEPTION; RATING-SCALE; ADOLESCENTS; FMRI AB Reflecting a paradigm shift in clinical neuroscience, many chronic psychiatric illnesses are now hypothesized to result from perturbed neural development. However, most work in this area focuses on schizophrenia. Here, we extend this paradigm to pediatric bipolar disorder (BID), thus demonstrating traction in the developmental psychobiology perspective. To study amygdala dysfunction, we examined neural mechanisms mediating face processing in 22 youths (mean age 14.21 +/- 3.11 yr) with BD and 21 controls of comparable age, gender, and IQ. Event-related functional MRI compared neural activation when attention was directed to emotional aspects of faces (hostility, subjects' fearfulness) vs. nonemotional aspects (nose width). Compared with controls, patients perceived greater hostility in neutral faces and reported more fear when viewing them. Also, compared with controls, patients had greater activation in the left amygdala, accumbens, putamen, and ventral prefrontal cortex when rating face hostility, and greater activation in the left amygdala and bilateral accumbens when rating their fear of the face. There were no between-group behavioral or neural differences in the nonemotional conditions. Results implicate deficient emotion-attention interactions in the pathophysiology of BD in youth and suggest that developmental psychobiology approaches to chronic mental illness have broad applicability. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. RP Rich, BA (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov FU Intramural NIH HHS NR 71 TC 195 Z9 198 U1 13 U2 24 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 JUN 6 PY 2006 VL 103 IS 23 BP 8900 EP 8905 DI 10.1073/pnas.0603246103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 053BK UT WOS:000238278400057 PM 16735472 ER PT J AU Hasler, G Kazuba, D Murphy, DL AF Hasler, G Kazuba, D Murphy, DL TI Factor analysis of obsessive-compulsive disorder YBOCS-SC symptoms and association with 5-HTTLPR SERT polymorphism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE factor analysis; endophenotype; symptom cluster; serotonin transporter ID SEROTONIN TRANSPORTER GENE; PROMOTER POLYMORPHISM; REGION POLYMORPHISM; PERSONALITY-TRAITS; REGULATORY REGION; TOURETTE-SYNDROME; COMORBIDITY; SLC6A4; DIMENSIONS; LINKAGE AB Symptoms defining obsessive-compulsive disorder (OCD) are diverse. Factor analyses of OCD symptoms have been used to evaluate obsessive-compulsive phenotypes that are thought to be more homogenous than the macro phenotype. There is evidence that three factors (symmetry/ ordering, obsessions/checking, and hoarding) are familial and preliminary evidence that repetitive rituals are associated with a functional polymorphism in the promotor region of the serotonin transporter gene (5-HTTLPR). The goal of this study was to examine relationships between OCD symptom dimensions and 5-HTTLPR. We genotyped 153 subjects who met DSM-IV criteria for OCD. We used the Yale-Brown obsessive-compulsive scale symptom checklist (YBOCS-SC) to assess OCD symptoms. Using principle components analysis, we derived four factors from the 13 symptom categories of the YBOCS-SC in this patient sample, which replicated previous factor analyses of this scale. The frequencies of the S allele and the SS genotype were associated with the second factor including obsessions regarding symmetry and compulsions involving repeating, counting, and ordering/arranging. This study may contribute to understanding of molecular genetic features underlying the appearance of symptom clusters in OCD. (c) 2006 Wiley-Liss, Inc. C1 Univ Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. NIMH, Clin Sci Lab, NIH, Bethesda, MD USA. RP Hasler, G (reprint author), Univ Hosp, Dept Psychiat, Culmannstr 8, CH-8091 Zurich, Switzerland. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Intramural NIH HHS NR 46 TC 41 Z9 43 U1 3 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUN 5 PY 2006 VL 141B IS 4 BP 403 EP 408 DI 10.1002/ajmg.b.30309 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 049YQ UT WOS:000238054200014 PM 16583440 ER PT J AU Sherman, M Carreon, J Schiffman, M AF Sherman, M. E. Carreon, J. D. Schiffman, M. CA ALTS Group TI Performance of cytology and human papillomavirus testing in relation to the menstrual cycle SO BRITISH JOURNAL OF CANCER LA English DT Article DE cervix; screening; cytology; human papillomavirus; menstrual cycle; epidemiology ID CERVICAL HUMAN-PAPILLOMAVIRUS; ATYPICAL SQUAMOUS-CELLS; PAPANICOLAOU SMEARS; VIRAL LOAD; UNDETERMINED SIGNIFICANCE; WOMEN; CANCER; CARCINOGENESIS; ABNORMALITIES; FLUCTUATIONS AB Cervical smears prepared around the time of menses have been linked to unsatisfactory specimens and false negative results; however, it is unclear whether liquid-based cytology is similarly affected and data relating date of last menstrual period (LMP) to human papillomavirus (HPV) DNA testing are conflicting. Accordingly, we evaluated liquid-based cytology and HPV test results using Hybrid Capture 2 and PCR by LMP ( days 0-10; 11-21; 22-28). We studied 5060 participants in ALTS, the Atypical Squamous Cells of Undetermined Significance ( ASCUS) Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. On average, women had 3.4 examinations ( median 4, range 1-5) during a 2-year period of observation permitting an examination of intra-individual variation in cytology and HPV by LMP. Although uncommon, unsatisfactory cytology specimens were most likely on days 0-10. For satisfactory specimens, the frequency with which cytologic categories were reported varied by time since LMP, although differences were modest and did not affect the chance of abnormal cytology or its severity among women diagnosed with CIN2+. The frequency of positive HC2 tests did not vary with date of LMP. Among HPV infected women, independent of eventual diagnosis and the number of viral genotypes present, mid-cycle specimens yielded the highest frequency of LSIL cytologic interpretations and the highest HPV load; however, the magnitude of these effects were small. Intraindividual correlations of cytology or HPV by LMP were generally weak. We conclude that mid-cycle specimens yield slightly higher HPV DNA loads and slightly increased LSIL interpretations, but the clinical impact is marginal. Standardizing collection times would slightly improve interpretation of trends in HPV load. Finally, these data are consistent with the view that the biological properties of the HPV-infected cervix vary with the date of the LMP. C1 NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. RP Sherman, M (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA. EM shermanm@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CN-155105, CN-55158, N01 CN055157, N01 CN055154, CN-55156, N01 CN055159, N01 CN055153] NR 39 TC 9 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 5 PY 2006 VL 94 IS 11 BP 1690 EP 1696 DI 10.1038/sj.bjc.6603151 PG 7 WC Oncology SC Oncology GA 048MH UT WOS:000237950700023 PM 16670716 ER PT J AU Troisi, R Hatch, E Titus-Ernstoff, L Palmer, JR Hyer, M Strohsnitter, WC Robboy, SJ Kaufman, R Herbst, A Adam, E Hoover, R AF Troisi, R. Hatch, E. E. Titus-Ernstoff, L. Palmer, J. R. Hyer, M. Strohsnitter, W. C. Robboy, S. J. Kaufman, R. Herbst, A. Adam, E. Hoover, R. N. TI Birth weight and breast cancer risk SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; birth weight; in utero exposure; oestrogens ID SUBSEQUENT RISK; CHILDHOOD GROWTH; SWEDISH COHORT; YOUNG-WOMEN; FOLLOW-UP; POPULATION; DIETHYLSTILBESTROL; MOTHERS; SIZE AB Exploring whether the positive association between birth weight and breast cancer risk differs by other breast cancer risk factors may help inform speculation about biological mechanism. In these data, high birth weight was associated with breast cancer risk in younger and in more educated women, but was not associated overall. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA. Boston Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Boston, MA 02118 USA. Informat Management Serv Inc, Bethesda, MD 20892 USA. Boston Univ, Slone Epidemiol Unit, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Methodist Hosp, Obstet & Gynecol Phys Org, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Baylor Univ, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7279 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928 NR 24 TC 9 Z9 9 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 5 PY 2006 VL 94 IS 11 BP 1734 EP 1737 DI 10.1038/sj.bjc.6603122 PG 4 WC Oncology SC Oncology GA 048MH UT WOS:000237950700029 PM 16641898 ER PT J AU Kudo-Saito, C Hodge, JW Kwak, H Kim-Schulze, S Schlom, J Kaufman, HL AF Kudo-Saito, C Hodge, JW Kwak, H Kim-Schulze, S Schlom, J Kaufman, HL TI 4-IBB ligand enhances tumor-specific immunity of poxvirus vaccines SO VACCINE LA English DT Article DE cancer; costimulation; 4-IBBL; poxviruses; vaccine ID CD8 T-CELLS; CARCINOEMBRYONIC ANTIGEN GENE; COLONY-STIMULATING FACTOR; 4-1BB LIGAND; ESTABLISHED TUMORS; ANTITUMOR IMMUNITY; DENDRITIC CELLS; IN-VIVO; COSTIMULATORY MOLECULES; EFFECTOR FUNCTION AB Purpose: Recombinant poxvirus vaccines have been explored as tumor vaccines. The immunogenicity of these vaccines can be enhanced by co-expressing costimulatory molecules and tumor-associated antigens. While the B7-CD28 interaction has been most comprehensively investigated, other costimulatory molecules utilize different signaling pathways and might provide further cooperation in T cell priming and survival. 4-1BB (CD137) is a TNF family member and is critical for activation and long-term maintenance of primed T cells. This study was conducted to determine if a poxvirus expressing the ligand for 4-1BB (4-1BBL) could further improve the immune and therapeutic responses of a previously reported poxvirus vaccine expressing a triad of costimulatory molecules (B7.1, ICAM-1, and LEA-3). Experimental design: A recombinant vaccinia virus expressing 4-1BBL was generated and characterized in an in vitro infection system. This vaccine was then used alone or in combination with a vaccinia virus expressing CEA, B7.1, ICAM-1, and LFA-3 in CEA-transgenic mice bearing established MC38 tumors. Tumor growth and immune responses against CEA and other tumor-associated antigens were determined. The level of anti-apoptotic proteins in responding T cells was determined by flow cytometry on tetramer selected T cells. Results: The combination of 4-1BBL with B7.1-based poxvirus vaccination resulted in significantly enhanced therapeutic effects against CEA-expressing tumors in a CEA-transgenic mouse model. This was associated with an increased level of CEA-specific CD4(+) and CD8(+) T cell responses, induction of antigen spreading to p53 and gp70, increased accumulation of CEA-specific T cells in the tumor microenvironment, and increased expression of bcl-X-L and bcl-2 in CD4(+) and CD8(+) T cells in vaccinated mice. Conclusion: 4-1BBL cooperates with B7 in enhancing anti-tumor and immunologic responses in a recombinant poxvirus vaccine model. The inclusion of costimulatory molecules targeting distinct T cell signaling pathways provides a mechanism for enhancing the therapeutic effectiveness of tumor vaccines. (c) 2006 Elsevier Ltd. All rights reserved. C1 Columbia Univ, Tumor Immunol Lab, New York, NY 10032 USA. NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kaufman, HL (reprint author), Columbia Univ, Tumor Immunol Lab, 177 Ft Washington Ave, New York, NY 10032 USA. EM hlk2003@columbia.edu RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [K08CA79881] NR 46 TC 28 Z9 31 U1 0 U2 1 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 JUN 5 PY 2006 VL 24 IS 23 BP 4975 EP 4986 DI 10.1016/j.vaccine.2006.03.042 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 056XD UT WOS:000238557500012 PM 16621183 ER PT J AU Wu, L Yang, ZY Xu, L Welcher, B Winfrey, S Shao, YM Mascola, JR Nabel, GJ AF Wu, L Yang, ZY Xu, L Welcher, B Winfrey, S Shao, YM Mascola, JR Nabel, GJ TI Cross-clade recognition and neutralization by the V3 region from clade C human immunodeficiency virus-1 envelope SO VACCINE LA English DT Article DE HIV-1; envelope; neutralizing antibodies ID CYTOTOXIC T-LYMPHOCYTES; HIV VACCINE CANDIDATE; ANTIBODY-RESPONSES; TYPE-1 ENVELOPE; ESCAPE; TRANSMISSION; IMMUNIZATION; GLYCOPROTEIN; IMMUNOGENICITY; EVOLUTION AB To understand the cross-reactivity of antibodies directed against variable regions of human immunodeficiency virus-1 (HIV-1) envelope (Env), chimeric immunogens were prepared from different clades with modifications in variable regions, and the resulting neutralizing antibody response was evaluated. The V3-specific neutralization activity induced by a clade B immunogen was limited to clade B viruses and was blocked by a clade B V3 peptide, but not by analogous clade A or C V3 peptides. In contrast, the V3 response elicited by a clade C immunogen cross-reacted with sensitive clade B viruses. The V3 region from a clade C virus, when introduced into a clade B sequence, elicited cross-clade activity, which could be reversed by V3 peptides derived from clades A and C. Thus, the anti-V3 antibody response elicited by a clade C immunogen could cross-react with heterologous clade viruses. Additionally, we describe a V I-specific immune response that mediated neutralization limited to the homologous HIV IIIB isolate and may be partially responsible for the commonly observed strain-specific neutralization responses elicited by vaccine immunogens. Published by Elsevier Ltd. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. China CDC, Natl Ctr AIDS STD Control & Prevent, Beijing 100050, Peoples R China. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Room 4502,Bldg 40,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU Intramural NIH HHS NR 31 TC 30 Z9 30 U1 0 U2 0 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 JUN 5 PY 2006 VL 24 IS 23 BP 4995 EP 5002 DI 10.1016/j.vaccine.2006.03.083 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 056XD UT WOS:000238557500014 PM 16690178 ER PT J AU Gomez-Roman, VR Grimes, GJ Potti, GK Peng, B Demberg, T Gravlin, L Treece, J Pal, R Lee, EM Alvord, WG Markham, PD Robert-Guroff, M AF Gomez-Roman, VR Grimes, GJ Potti, GK Peng, B Demberg, T Gravlin, L Treece, J Pal, R Lee, EM Alvord, WG Markham, PD Robert-Guroff, M TI Oral delivery of replication-competent adenovirus vectors is well tolerated by SIV- and SHIV-infected rhesus macaques SO VACCINE LA English DT Article DE replication-competent adenovirus vectors; rhesus macaque; SIV/SHIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIPLOID TISSUE CULTURE; IMMUNE-RESPONSES; SELECTIVE INFECTION; SIVMAC251 CHALLENGE; CELLULAR-IMMUNITY; VACCINE REGIMEN; COTTON RATS; LIVE; IMMUNIZATION AB Although replication-competent adenovirus (Ad) vectors are promising in AIDS vaccine design, their safety in immune compromised hosts is unknown. To initially address this question, enteric-coated tablets containing a replicating Ad vector were orally administered to SHIV and SIV-infected rhesus macaques with normal, intermediate or low CD4 T cell counts and stable disease. The vector was detected within a week after tablet administration in stools of all animals but not in nasal secretions, indicating no spread of virus to the upper respiratory tract. CD4 T cell counts and viral loads remained stable in all animals and no signs of fever, weight loss, or other clinical symptoms of Ad-induced disease were observed during 10 weeks of follow-up. Oral delivery of the replicating Ad vector was safe and well tolerated by SHIV- and SIV-infected hosts. Oral enteric-coated tablets may prove safe for administering replicating Ad-vectored vaccines in areas with high HIV prevalence. Published by Elsevier Ltd. C1 NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Robert-Guroff, M (reprint author), NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. EM guroffm@exchange.nih.gov NR 44 TC 16 Z9 17 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 JUN 5 PY 2006 VL 24 IS 23 BP 5064 EP 5072 DI 10.1016/j.vaccine.2006.03.048 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 056XD UT WOS:000238557500021 PM 16621178 ER PT J AU Adamec, R Burton, P Blundell, J Murphy, DL Holmes, A AF Adamec, R Burton, P Blundell, J Murphy, DL Holmes, A TI Vulnerability to mild predator stress in serotonin transporter knockout mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE anxiety; cat odor exposure; elevated plus maze; factor analysis; hole board; lasting effects; light/dark box; light-enhancement; 5-HTT knockout mice; mice; PTSD; startle; SERT ID ANXIETY-LIKE BEHAVIOR; LONG-TERM POTENTIATION; LIGHT-ENHANCED STARTLE; POSTTRAUMATIC-STRESS; SEX-DIFFERENCES; NEURAL PLASTICITY; TRAUMATIC STRESS; ANIMAL-MODEL; CAT ODOR; DEFENSIVE BEHAVIORS AB Effect of predator stress on rat and mouse anxiety-like behavior may model aspects of post traumatic stress disorder (PTSD). A single cat exposure of wild type (C57, CFW) mice can produce lasting anxiety-like effects in the elevated plus maze, light/dark box tests and startle. In addition, female but not male C57 mice are made more anxious in the plus maze by exposure to predator odors alone, suggesting differential vulnerability to predator stressors of differing intensity. There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans. This prompted the generation of SERT knockout mice [see Holmes A, Murphy DL, Crawley JN. Biol Psychiatry 2003;54(10):953-9]. Present work used these mice to determine if there was a link between vulnerability to the anxiogenic effects of predator odors and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake. Wild type (WT, C57 background), heterozygous (SERT +/-, HET) mice and homozygous knockout (SERT -/-, KO) were assigned to handled control groups or groups exposed for 10 min to a large testing room rich in cat odor. One week after handling or room exposure, anxiety testing took place in the dark phase of the light/dark cycle, in red light. Predator odor exposure was selectively anxiogenic in the plus maze and light/dark box tests in SERT -/- mice. Exposure to predator odor did not potentiate startle. Findings suggest a role for abnormalities in 5-HT transmission in vulnerability to some of the lasting anxiogenic effects of species relevant stressors and possibly in vulnerability to PTSD. (c) 2006 Elsevier B.V All rights reserved. C1 Mem Univ Newfoundland, Dept Psychol, St John, NF A1B 3X9, Canada. NIMH, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NIMH, NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet,NIH, Bethesda, MD 20892 USA. RP Adamec, R (reprint author), Mem Univ Newfoundland, Dept Psychol, 232 Elizabeth Ave, St John, NF A1B 3X9, Canada. EM radamec@mun.ca NR 75 TC 75 Z9 77 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUN 3 PY 2006 VL 170 IS 1 BP 126 EP 140 DI 10.1016/j.bbr.2006.02.012 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 047KW UT WOS:000237879200016 PM 16546269 ER PT J AU Milman, A Weizman, R Rigai, T Rice, KC Pick, CG AF Milman, A Weizman, R Rigai, T Rice, KC Pick, CG TI Behavioral effects of opioid subtypes compared with benzodiazepines in the staircase paradigm SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE staircase test; lorazepam; tifluadome; morphine; U50-488H; SNC80; nalorphine; mice ID ELEVATED PLUS-MAZE; NITROUS-OXIDE; MORPHINE; RECEPTOR; MOUSE; MICE; RATS; ANTAGONIST; NALOXONE; AGENTS AB Opioid abuse is frequently associated with the abuse of benzodiazepines (BZ). Despite the fact that benzodiazepines and opioids act at totally separate receptor sites and through different biochemical and pharmacological mechanisms, they obviously interact with each other at some level. The present study was designed to investigate the behavioral effects of agents with activity on the opioid system and with the benzodiazepine receptor complex in the staircase paradigm. The benzodiazepine agonist lorazepam was used as a reference drug and showed a benzodiazepine effect: it reduced the rearing activity in mice in a dose-dependent manner, at doses that did not suppress climbing. Dissociation between the rearing and climbing behavior was not obtained with the administration of the opioid benzodiazepine, tifluadome, although tifluadome was antagonized by the BZ antagonist, flumazenil and not by naloxone, an opioid antagonist. An administration of opioids that act on the different subtype receptors morphine, U50 and SNC80, induced a dose dependent decrease in both the rearing and climbing activity, meaning no behavioral dissociation. Naloxone was found to have an antagonistic effect on morphine and U50-488H (mu and K subtype receptors, respectively), but no antagonistic effect on the 8 subtype receptor agonist, SNC80. The administration of nalorphine to mice had no effect on both the rearing and climbing, in the staircase paradigm. When combining naloxone with the mentioned nalorphine, results showed the same effect, which was achieved with all the other opiates. This data, once again, supports the validity of the mouse staircase test for the identification of anxiolytic agents with a GABA(A) receptor complex-mediated activity, and for the ability to differentiate between diverse effects of the different opioids. (c) 2006 Elsevier B.V. All rights reserved. C1 Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Psychiat, IL-69978 Tel Aviv, Israel. Tel Aviv Community Mental Hlth Ctr, Tel Aviv, Israel. NIDDK, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Pick, CG (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. EM anatmilman@gmail.com; weizmana@post.tau.ac.il; tovarigai@post.tau.ac.il; ricek@bdg8.niddk.nih.gov; pickc@post.tau.ac.il RI Pick, Chaim/D-4789-2009 NR 30 TC 11 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD JUN 3 PY 2006 VL 170 IS 1 BP 141 EP 147 DI 10.1016/j.bbr.2006.02.017 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 047KW UT WOS:000237879200017 PM 16574254 ER PT J AU Huang, WC Umbach, DM Ohler, U Li, LP AF Huang, Weichun Umbach, David M. Ohler, Uwe Li, Leping TI Optimized mixed Markov models for motif identification SO BMC BIOINFORMATICS LA English DT Article ID FACTOR-BINDING-SITES; INFORMATION-CONTENT; GENE; SEQUENCES; DNA; MUTATIONS; SIGNALS; CHAINS AB Background: Identifying functional elements, such as transcriptional factor binding sites, is a fundamental step in reconstructing gene regulatory networks and remains a challenging issue, largely due to limited availability of training samples. Results: We introduce a novel and flexible model, the Optimized Mixture Markov model (OMiMa), and related methods to allow adjustment of model complexity for different motifs. In comparison with other leading methods, OMiMa can incorporate more than the NNSplice's pairwise dependencies; OMiMa avoids model over-fitting better than the Permuted Variable Length Markov Model (PVLMM); and OMiMa requires smaller training samples than the Maximum Entropy Model (MEM). Testing on both simulated and actual data ( regulatory cis-elements and splice sites), we found OMiMa's performance superior to the other leading methods in terms of prediction accuracy, required size of training data or computational time. Our OMiMa system, to our knowledge, is the only motif finding tool that incorporates automatic selection of the best model. OMiMa is freely available at [ 1]. Conclusion: Our optimized mixture of Markov models represents an alternative to the existing methods for modeling dependent structures within a biological motif. Our model is conceptually simple and effective, and can improve prediction accuracy and/or computational speed over other leading methods. C1 N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27606 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC 27708 USA. RP Huang, WC (reprint author), N Carolina State Univ, Bioinformat Res Ctr, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM huang6@niehs.nih.gov; umbach@niehs.nih.gov; uwe.ohler@duke.edu; li3@niehs.nih.gov FU Intramural NIH HHS NR 41 TC 11 Z9 11 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 2 PY 2006 VL 7 AR 279 DI 10.1186/1471-2105-7-279 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 073IO UT WOS:000239736400001 PM 16749929 ER PT J AU Noma, KI Cam, HP Maraia, RJ Grewal, SIS AF Noma, KI Cam, HP Maraia, RJ Grewal, SIS TI A role for TFIIIC transcription factor complex in genome organization SO CELL LA English DT Article ID RNA-POLYMERASE-III; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; HETEROCHROMATIN DOMAIN; EPIGENETIC CONTROL; CHROMATIN DOMAINS; GENE-EXPRESSION; BOUNDARIES; MACHINERY AB Eukaryotic genome complexity necessitates boundary and insulator elements to partition genomic content into distinct domains. We show that inverted repeat (IR) boundary elements flanking the fission yeast mating-type heterochromatin domain contain B-box sequences, which prevent heterochromatin from spreading into neighboring euchromatic regions by recruiting transcription factor TFIIIC complex without RNA polymerase III (Pol III). Genome-wide analysis reveals TFIIIC with Pol III at all tRNA genes, many of which cluster at pericentromeric heterochromatin domain boundaries. However, a single tRNA(phe), gene with modest TFIIIC enrichment is insufficient to serve as boundary and requires RNAi-associated element to restrain heterochromatin spreading. Remarkably, we found TFIIIC localization without Pol III at many sites located between divergent promoters. These sites appear to act as chromosome-organizing clamps by tethering distant loci to the nuclear periphery, at which TFIIIC: is concentrated into several distinct bodies. Our analyses uncover a general genome organization mechanism involving conserved TFIIIC complex. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU Intramural NIH HHS NR 48 TC 176 Z9 184 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 2 PY 2006 VL 125 IS 5 BP 859 EP 872 DI 10.1016/j.cell.2006.04.028 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 050VG UT WOS:000238116400014 PM 16751097 ER PT J AU Wang, H DellaVecchia, MJ Skorvaga, M Croteau, DL Erie, DA Van Houten, B AF Wang, H DellaVecchia, MJ Skorvaga, M Croteau, DL Erie, DA Van Houten, B TI UvrB domain 4, an autoinhibitory gate for regulation of DNA binding and ATPase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; UVRABC NUCLEASE SYSTEM; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; (A)BC EXCINUCLEASE; THERMUS-THERMOPHILUS; PREINCISION COMPLEX; DAMAGE RECOGNITION; DEPENDENT ATPASE; PROTEIN COMPLEX AB UvrB, a central DNA damage recognition protein in bacterial nucleotide excision repair, has weak affinity for DNA, and its ATPase activity is activated by UvrA and damaged DNA. Regulation of DNA binding and ATP hydrolysis by UvrB is poorly understood. Using atomic force microscopy and biochemical assays, we found that truncation of domain 4 of Bacillus caldotenax UvrB (UvrB Delta 4) leads to multiple changes in protein function. Protein dimerization decreases with an similar to 8-fold increase of the equilibrium dissociation constant and an increase in DNA binding. Loss of domain 4 causes the DNA binding mode of UvrB to change from dimer to monomer, and affinity increases with the apparent dissociation constants on nondamaged and damaged single-stranded DNA decreasing 22- and 14-fold, respectively. ATPase activity by UvrB Delta 4 increases 14- and 9-fold with and without single-stranded DNA, respectively, and UvrB Delta 4 supports UvrA-independent damage-specific incision by Cho on a bubble DNA substrate. We propose that other than its previously discovered role in regulating protein-protein interactions, domain 4 is an autoinhibitory domain regulating the DNA binding and ATPase activities of UvrB. C1 NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Slovak Acad Sci, Inst Canc Res, Dept Mol Genet, Bratislava 83391, Slovakia. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Van Houten, B (reprint author), NIEHS, Mol Genet Lab, NIH, Dept Hlth & Human Serv, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM vanhout1@niehs.nih.gov RI Wang, Hong/F-3164-2014 OI Wang, Hong/0000-0003-0165-3559 FU Intramural NIH HHS NR 49 TC 32 Z9 32 U1 1 U2 3 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 JUN 2 PY 2006 VL 281 IS 22 BP 15227 EP 15237 DI 10.1074/jbc.M601476200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200026 PM 16595666 ER PT J AU Potrykus, K Vinella, D Murphy, H Szalewska-Palasz, A D'Ari, R Cashel, M AF Potrykus, K Vinella, D Murphy, H Szalewska-Palasz, A D'Ari, R Cashel, M TI Antagonistic regulation of Escherichia coli ribosomal RNA rrnB P1 promoter activity by GreA and DksA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPT CLEAVAGE FACTORS; POLYMERASE SECONDARY CHANNEL; CRYSTAL-STRUCTURE; IN-VITRO; MOLECULAR-MECHANISM; ANGSTROM RESOLUTION; STRINGENT CONTROL; MICROCIN J25; PPGPP; INITIATION AB The Escherichia coli proteins DksA, GreA, and GreB are all structural homologs that bind the secondary channel of RNApolymerase ( RNAP) but are thought to act at different levels of transcription. DksA, with its co-factor ppGpp, inhibits rrnB P1 transcription initiation, whereas GreA and GreB activate RNAP to cleave backtracked RNA during elongational pausing. Here, in vivo and in vitro evidence reveals antagonistic regulation of rrnB P1 transcription initiation by Gre factors ( particularly GreA) and DksA; GreA activates and DksA inhibits. DksA inhibition is epistatic to GreA activation. Both modes of regulation are ppGpp-independent in vivo but DksA inhibition requires ppGpp in vitro. Kinetic experiments and studies of rrnB P1-RNA polymerase complexes suggest that GreA mediates conformational changes at an initiation step in the absence of NTP substrates, even before DksA acts. GreA effects on rrnB P1 open complex conformation reveal a new feature of GreA distinct from its general function in elongation. Our findings support the idea that a balance of the interactions between the three secondary channel-binding proteins and RNAP can provide a new mode for regulating transcription. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Paris 06, CNRS, Inst Jacques Monod, F-7251 Paris 05, France. Univ Paris 07, CNRS, Inst Jacques Monod, F-7251 Paris 05, France. RP Cashel, M (reprint author), NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM mcashel@nih.gov RI vinella, daniel/G-5504-2012 FU Intramural NIH HHS NR 41 TC 42 Z9 45 U1 1 U2 6 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 JUN 2 PY 2006 VL 281 IS 22 BP 15238 EP 15248 DI 10.1074/jbc.M601531200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200027 PM 16597620 ER PT J AU Liu, XB Bandyopadhyay, B Nakamoto, T Singh, B Liedtke, W Melvin, JE Ambudkar, I AF Liu, XB Bandyopadhyay, B Nakamoto, T Singh, B Liedtke, W Melvin, JE Ambudkar, I TI A role for AQP5 in activation of TRPV4 by hypotonicity - Concerted involvement of AQP5 and TRPV4 in regulation of cell volume recovery SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CATION CHANNEL TRPV4; SALIVARY-GLAND; EPITHELIAL-CELLS; ACINAR-CELLS; MEMBRANE; CALCIUM; TRANSLOCATION; IDENTIFICATION; LOCALIZATION; AQUAPORIN-5 AB Regulation of cell volume in response to changes in osmolarity is critical for cell function and survival. However, the molecular basis of osmosensation and regulation of cell volume are not clearly understood. We have examined the mechanism of regulatory volume decrease ( RVD) in salivary gland cells and report a novel association between osmosensing TRPV4 ( transient receptor potential vanalloid 4) and AQP5 ( aquaporin 5), which is required for regulating water permeability and cell volume. Exposure of salivary gland cells and acini to hypotonicity elicited an increase in cell volume and activation of RVD. Hypotonicity also activated Ca2+ entry, which was required for subsequent RVD. Ca2+ entry was associated with a distinct nonselective cation current that was activated by 4 alpha PDD and inhibited by ruthenium red, suggesting involvement of TRPV4. Consistent with this, endogenous TRPV4 was detected in cells and in the apical region of acini along AQP5. Importantly, acinar cells from mice lacking either TRPV4 or AQP5 displayed greatly reduced Ca2+ entry and loss of RVD in response to hypotonicity, although the extent of cell swelling was similar. Expression of N terminus-deleted AQP5 suppressed TRPV4 activation and RVD but not cell swelling. Furthermore, hypotonicity increased the association and surface expression of AQP5 and TRPV4. Both these effects and RVD were reduced by actin depolymerization. These data demonstrate that ( i) activation of TRPV4 by hypotonicity depends on AQP5, not on cell swelling per se, and ( ii) TRPV4 and AQP5 concertedly control regulatory volume decrease. These data suggest a potentially important role for TRPV4 in salivary gland function. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Ctr Oral Biol, Rochester, NY 14642 USA. Univ N Dakota, Dept Biochem & Mol Biol, Grand Forks, ND 58203 USA. Duke Univ, Med Ctr, Ctr Translat Neurosci, Durham, NC 27710 USA. RP Ambudkar, I (reprint author), NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bldg 10 Rm 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov RI Liedtke, Wolfgang/G-4633-2011; OI Singh, Brij/0000-0003-0535-5997 FU NIDCR NIH HHS [DE013823] NR 39 TC 121 Z9 134 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 JUN 2 PY 2006 VL 281 IS 22 BP 15485 EP 15495 DI 10.1074/jbc.M600549200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 048BI UT WOS:000237922200055 PM 16571723 ER PT J AU Boillee, S Yamanaka, K Lobsiger, CS Copeland, NG Jenkins, NA Kassiotis, G Kollias, G Cleveland, DW AF Boillee, S Yamanaka, K Lobsiger, CS Copeland, NG Jenkins, NA Kassiotis, G Kollias, G Cleveland, DW TI Onset and progression in inherited ALS determined by motor neurons and microglia SO SCIENCE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; SPINAL-CORD TISSUE; FAMILIAL ALS; MOUSE MODEL; TRANSGENIC MODEL; DISEASE ONSET; DEGENERATION; MINOCYCLINE; MICE AB Dominant mutations in superoxide dismutase cause amyotrophic lateral sclerosis (ALS), a progressive paralytic disease characterized by loss of motor neurons. With the use of mice carrying a deletable mutant gene, expression within motor neurons was shown to be a primary determinant of disease onset and of an early phase of disease progression. Diminishing the mutant levels in microglia had little effect on the early disease phase but sharply slowed later disease progression. Onset and progression thus represent distinct disease phases defined by mutant action within different cell types to generate non-cell-autonomous killing of motor neurons; these findings validate therapies, including cell replacement, targeted to the non-neuronal cells. C1 Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Biomed Sci Res Ctr Alexander Fleming, Inst Immunol, Vari 16672, Greece. RP Yamanaka, K (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM kyamanaka@ucsd.edu; dcleveland@ucsd.edu RI Kollias, George/A-7079-2012; Yamanaka, Koji/H-5806-2011 OI Kollias, George/0000-0003-1867-3150; Yamanaka, Koji/0000-0003-4655-0035 FU NINDS NIH HHS [NS 27036, R37 NS027036] NR 28 TC 787 Z9 808 U1 7 U2 46 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 2 PY 2006 VL 312 IS 5778 BP 1389 EP 1392 DI 10.1126/science.1123511 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 048QM UT WOS:000237961600058 PM 16741123 ER PT J AU Cheng, TL Johnson, S Wright, JL Pearson-Fields, AS Brenner, R Schwarz, D O'Donnell, R Scheidt, PC AF Cheng, TL Johnson, S Wright, JL Pearson-Fields, AS Brenner, R Schwarz, D O'Donnell, R Scheidt, PC TI Assault-injured adolescents presenting to the emergency department: Causes and circumstances SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE adolescent injury; youth violence; assault; emergency department ID COMMUNITY VIOLENCE PROJECT; YOUTH VIOLENCE; PSYCHOSOCIAL ADJUSTMENT; BULLYING BEHAVIORS; PROTECTIVE FACTORS; RISK; INTERVENTION; CONSEQUENCES; TELEPHONE; EVENTS AB Objectives: To describe the causes and circumstances of conflict leading to assault injury among urban youth seeking care in the emergency department. Methods: The authors conducted in-person and telephone interviews with a convenience sample of 143 youth aged 12-19 years presenting to two urban emergency departments with an interpersonal assault injury. Patients were interviewed about the nature and circumstances of their injury. Descriptive analysis was performed, including stratified analysis by gender, age (12-15 vs. 16-19 years), and weapon use. Results: Seventy percent of patients knew or knew of the person(s) who injured them; most were friends, classmates, or acquaintances. More than half of the injuries (56%) were related to a past disagreement. Among assaults related to a past disagreement, 33% of patients had previous arguments with their assailant, 16% had previous fights, and 14% had previous weapons threats. Twenty-nine percent had been previously threatened, and 11% had previously threatened their assailant. Twenty-eight percent of patients believed they helped to cause the injury by provoking a fight or letting down their guard. Nearly two thirds (64%) believed there were things they could change to prevent future injury, including staying away from dangerous situations and bad influences or controlling their tempers. Conclusions: Most assault injuries among adolescents involved past disagreements with people they knew. Many injured youth were mutually involved in conflict before their injury. Over time, many victims and perpetrators may be interchangeable. These data may help inform emergency department-based interventions to prevent assault injury. C1 Johns Hopkins Univ, Div Gen Pediat & Adolescent Med, Dept Pediat, Baltimore, MD 21287 USA. Univ Calif San Francisco, Ctr Hlth & Community, San Francisco, CA 94143 USA. Childrens Res Inst, Washington, DC USA. George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Emergency Med, Washington, DC USA. Mautner Project, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Craig Dalsimer Div Adolescent Med, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Cheng, TL (reprint author), Johns Hopkins Univ, Div Gen Pediat & Adolescent Med, Dept Pediat, 600 N Wolfe St,Pk 392, Baltimore, MD 21287 USA. EM tcheng2@jhmi.edu FU NIMHD NIH HHS [P20 MD00165]; PHS HHS [R40MC00174, R49/CCR331657] NR 37 TC 24 Z9 24 U1 4 U2 6 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD JUN PY 2006 VL 13 IS 6 BP 610 EP 616 AR PII ISSN 1069-6563583 DI 10.1197/j.aem.2006.01.011 PG 7 WC Emergency Medicine SC Emergency Medicine GA 051NF UT WOS:000238167100004 PM 16609105 ER PT J AU Dores, GM Chang, S Berger, VW Perkins, SN Hursting, SD Weed, DL AF Dores, GM Chang, S Berger, VW Perkins, SN Hursting, SD Weed, DL TI Evaluating research training outcomes: Experience from the Cancer Prevention Fellowship Program at the National Cancer Institute SO ACADEMIC MEDICINE LA English DT Article ID RESEARCH PRODUCTIVITY; FAMILY MEDICINE; FACULTY AB Purpose The authors describe an evaluation approach to assess research training that is easy to implement, takes into account individual experience and diversity in research disciplines, and can be adapted to measure various outcomes, depending upon program goals. Method Using publications as the outcome measure, the authors analyzed data from 66 trainees in the National Cancer Institute's Cancer Prevention Fellowship Program (CPFP) to illustrate this evaluation strategy. For postdoctoral fellows entering the CPFP between 1987 and 1997, the authors considered the three-year period prior to entry in the CPFP (pre-CPFP), the period during training, and the three-year period after completion of the CPFP (post-CPFP). Summary measures for individuals' publications during each of the three time periods were calculated, and the probability of change in total, peer-reviewed, and first-authored publications post-CPFP compared to pre-CPFP was assessed. Results Compared to pre-CPFP, the CPFP fellows published significantly more total, peer-reviewed, and first-authored publications post-CPFP. Post-CPFP younger individuals published more than older fellows. MDs had a greater increase in publications over time than did PhDs, but both groups had similar overall numbers of publications post-CPFP. Individuals pursuing a master of public health degree during training published more post-CPFP than did those who did not pursue this training in the program. Conclusions Training programs facing the challenge of evaluating research outcomes will require new evaluation methods that take into account program goals. This easily adaptable, longitudinal evaluation strategy allows for diversity in research disciplines and research experience and can inform programmatic needs and individual progress. C1 NCI, Off Prevent Oncol,Div Canc Prevent, NIH,Biometry Res Grp, US Dept HHS, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Austin, TX 78712 USA. RP Dores, GM (reprint author), NCI, Off Prevent Oncol,Div Canc Prevent, NIH,Biometry Res Grp, US Dept HHS, 6130 Execut Blvd,Execut Plaza N,Suite 321, Bethesda, MD 20892 USA. EM doresg@mail.nih.gov NR 19 TC 13 Z9 13 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUN PY 2006 VL 81 IS 6 BP 535 EP 541 DI 10.1097/01.ACM.0000225216.07584.b0 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 048RB UT WOS:000237963100007 PM 16728801 ER PT J AU Radaev, S Li, S Sun, PD AF Radaev, S Li, S Sun, PD TI A survey of protein-protein complex crystallizations SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID DESIGN AB A survey of crystallization conditions was carried out for 650 published protein-protein complexes in the Protein Data Bank ( PDB) of the Research Collaboratory for Structural Bioinformatics ( RCSB). This resulted in the establishment of a Protein Complex Crystallization Database ( PCCD) and a set of configuration-space boundaries for protein-complex crystallizations. Overall, polyethylene glycol ( PEG) based conditions accounted for 70-80% of all crystallizations, with PEG 3000-4000, 5000-6000 and 8000 being the most frequently used. The median values of PEG concentrations were between 10 and 20% and were inversely correlated with their molecular weights. Ammonium sulfate remained the most favorable salt precipitant, with a median concentration of 1.6 M. The crystallization pH for the vast majority of protein complexes was between 5.0 and 8.0. Overall, the boundaries for the crystallization configuration space of protein complexes appear to be more restricted than those of soluble proteins. This may reflect the limited stability and solubility of protein protein complexes. Based on statistical analysis of the database, a sparse-matrix and a systematic buffer and pH screen were formulated to best represent the crystallization of protein complexes. C1 NIAID, Struct Immunol Sect, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov NR 18 TC 21 Z9 22 U1 0 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUN PY 2006 VL 62 BP 605 EP 612 DI 10.1107/S0907444906011735 PN 6 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 041QR UT WOS:000237471300006 PM 16699187 ER PT J AU Schiffmann, R AF Schiffmann, Raphael TI Neuropathy and Fabry disease: pathogenesis and enzyme replacement therapy SO ACTA NEUROLOGICA BELGICA LA English DT Review DE Fabry disease; peripheral neuropathy; neuropathic pain; enzyme replacment therapy ID PERIPHERAL-NERVE INVOLVEMENT; SMALL FIBER DYSFUNCTION; FEMALE CARRIER; PAIN; INNERVATION; PHENOTYPE; MECHANISM; DIAGNOSIS; GANGLIA; SYNCOPE AB The neurological manifestations of Fabry disease include both peripheral and central nervous system involvement caused by a deficiency of alpha-galactosidase A and accumulation of alpha-D-galactosyl moieties, particularly globotriosylceramide accumulation (Gb(3)). These are found in Schwann cells and dorsal root ganglia together with deposits in central nervous system neurons. Involvement of the peripheral nervous system affect mainly small A delta and C fibers and are likely causally related to the altered autonomic function and neuropathic pain found in this disorder Other related abnormalities to be discussed are hypohidrosis and other abnormalities attributed to autonomic nervous system dysfunction. The function of the peripheral nervous system is somewhat improved by ERT with reduction in neuropathic pain and an improvement of the detection threshold for cold and warm sensation in the hand and foot. Improvement in sweating and heat tolerance is also noted following ERT Despite those positive results, ERT does not normalize the function of the peripheral nervous system. C1 Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bldg 10 Room 3D03, Bethesda, MD 20892 USA. EM rs4e@nih.gov NR 48 TC 13 Z9 17 U1 0 U2 0 PU ACTA MEDICA BELGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138-A, B-1180 BRUSSELS, BELGIUM SN 0300-9009 J9 ACTA NEUROL BELG JI Acta Neurol. Belg. PD JUN PY 2006 VL 106 IS 2 BP 61 EP 65 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 063ON UT WOS:000239029200003 PM 16898255 ER PT J AU Dawson, DA Grant, BF Stinson, FS Chou, PS AF Dawson, DA Grant, BF Stinson, FS Chou, PS TI Estimating the effect of help-seeking on achieving recovery from alcohol dependence SO ADDICTION LA English DT Article DE dependence; help-seeking; recovery; treatment; 12-step ID NATIONAL EPIDEMIOLOGIC SURVEY; USE DISORDER CRITERIA; DSM-IV ALCOHOL; UNITED-STATES; BRIEF INTERVENTIONS; AUDADIS-ADR; PREVALENCE; OUTCOMES; CONCORDANCE; DIAGNOSES AB Aims To investigate the effect of help-seeking on the likelihood of recovery from Diagnostic and Statistical Manual version IV (DSM-IV) alcohol dependence, specifically examining the impact of model selection, factors that moderate the effect of help-seeking and distinctions between the effects of 12-Step participation and formal treatment. Methods This analysis is based on data from the Wave 1 2001-02 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a cross-sectional, retrospective survey of a nationally representative sample of US adults 18 years of age and over. The analytical sample consisted of 4422 individuals with prior-to-past-year (PPY) onset of DSM-IV alcohol dependence. Findings Logistic regression, proportional hazards and time-dependent proportional hazards models were used to estimate the effects of help-seeking on three outcomes: (1) any recovery from alcohol dependence, which required full remission of all symptoms of alcohol abuse and dependence and excluded asymptomatic drinkers whose alcohol consumption exceeded low-risk drinking guidelines; (2) non-abstinent recovery (NR), representing low-risk asymptomatic drinkers; and (3) abstinent recovery (AR), representing abstainers. Findings Only one-quarter of individuals with PPY-onset alcohol dependence had ever sought help for alcohol problems, including 3.1% who had participated in 12-Step programs only, 5.4% who had received formal treatment only and 17.0% with both 12-Step and formal treatment. Based on the most appropriate model, help-seeking increased the likelihood of any recovery [hazard rate ratio (HRR) = 2.38], NR (HRR = 1.50) and AR (HRR = 4.01). The impact of help-seeking on AR did not show any significant variation across the exposure period but was modified by severity among other factors. Individuals who participated in 12-Step programs in addition to formal treatment had almost twice the chance of recovery and more than more than twice the chance of AR compared with those who received formal treatment alone. Conclusions Help-seeking plays a significant role in the achievement of abstinent recovery from alcohol dependence, with 12-Step participation playing a major role. Appropriate model selection is critical to assessing the impact of help-seeking. C1 NIAAA, LEB, NIH, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, LEB, NIH, Div Intramural Clin & Biol Res, Room 3083,5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov FU Intramural NIH HHS NR 38 TC 83 Z9 83 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 2006 VL 101 IS 6 BP 824 EP 834 DI 10.1111/j.1360-0443.2006.01433.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 042GO UT WOS:000237516100013 PM 16696626 ER PT J AU Conway, KP Compton, WM Miller, PM AF Conway, KP Compton, WM Miller, PM TI Editorial - Novel approaches to phenotyping drug abuse SO ADDICTIVE BEHAVIORS LA English DT Editorial Material C1 NIDA, Div Clin Neurosci & Behav Res, NIH, DHHS, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. NIDA, Div Epidemiol Serv & Prevent Res, NIH, DHHS, Bethesda, MD 20892 USA. RP Conway, KP (reprint author), NIDA, Div Clin Neurosci & Behav Res, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUN PY 2006 VL 31 IS 6 BP 923 EP 928 DI 10.1016/S036-4603(06)00146-8 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 057UM UT WOS:000238620700001 ER PT J AU Ten Eyck, TA Thede, D Bode, G Bourquin, L AF Ten Eyck, Toby A. Thede, Donna Bode, Gerd Bourquin, Leslie TI Is HACCP nothing? A disjoint constitution between inspectors, processors, and consumers and the cider industry in Michigan SO AGRICULTURE AND HUMAN VALUES LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Rural-Sociological-Society CY AUG 11, 2004 CL Sacramento, CA SP Rural Sociol Soc DE cider industry; communication; food safety; HACCP; Michigan ID FOOD IRRADIATION; KNOWLEDGE; SAFETY AB The transmission of a product or idea from one culture or point of origin to another and the maintenance of control outside the new locality has been referred to as the distribution and maintenance of "nothing." This perspective has been used to describe the global marketplace and the influence of large multinational corporations on the politics and cultures of host countries. This paper uses this concept, but within a much smaller context. Using the sensitizing concept of a "disjoint constitution," we interviewed health inspectors and apple cider producers in Michigan to determine if the implementation of the Hazard Analysis and Critical Control Points (HACCP) program designed to ensure food safety was characterized by a power differential that would favor the inspectors. In addition, a larger survey of processors and an internet survey of apple cider consumers was conducted to supplement this data. It was found that HACCP had characteristics of both "nothing" and "something" and that better communication is needed between these groups to move it further along toward the something end of the continuum. C1 Michigan State Univ, Dept Sociol, E Lansing, MI 48824 USA. Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA. Kellogg Co, Nutr & Regulatory Affairs, Battle Creek, MI 49016 USA. Natl Canc Inst, Div Canc Prevent, NIH, Bethesda, MD USA. Michigan State Univ, Natl Food Safety & Toxicol Ctr, Dept Food Sci & Nutr, E Lansing, MI 48824 USA. Michigan State Univ, Food Safety Policy Ctr, E Lansing, MI 48824 USA. RP Ten Eyck, TA (reprint author), Michigan State Univ, Dept Sociol, 316 Berkey Hall, E Lansing, MI 48824 USA. EM teneyck@msu.edu RI Diaz, Belen/B-8946-2012 NR 31 TC 7 Z9 7 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0889-048X J9 AGR HUM VALUES JI Agric. Human Values PD SUM PY 2006 VL 23 IS 2 BP 205 EP 214 DI 10.1007/s10460-005-6107-4 PG 10 WC Agriculture, Multidisciplinary; History & Philosophy Of Science; Sociology SC Agriculture; History & Philosophy of Science; Sociology GA 064XB UT WOS:000239122900005 ER PT J AU Chattopadhyay, PK Douek, DC Gange, SJ Chadwick, KR Hellerstein, M Margolick, JB AF Chattopadhyay, PK Douek, DC Gange, SJ Chadwick, KR Hellerstein, M Margolick, JB TI Longitudinal assessment of de novo T cell production in relation to HIV-associated T cell homeostasis failure SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; RECEPTOR EXCISION CIRCLES; SYNCYTIUM-INDUCING PHENOTYPE; RECENT THYMIC EMIGRANTS; VIRUS TYPE-1 INFECTION; CD4 LYMPHOCYTES; FLOW-CYTOMETRY; AIDS; PROGRESSION; SUPPRESSION AB Loss of circulating CD4(+) T cells in HIV-1 disease is balanced by CD8(+) lymphocytosis to maintain normal CD3(+) T cell counts [blind T cell homeostasis (TCH)]. However, for unknown reasons TCH generally fails 1.5-2.5 years before clinically defined AIDS. We investigated whether TCH failure was associated with changes in thymic production of T cells. Using specimens stored prospectively in the Multicenter AID Cohort Study (MACS), we measured expression of signal-joint T cell receptor excision circles (sjTRECs), a marker for thymic T cell production, and the fraction of proliferating naive and memory T cells during a 6-8 year period bracketing TCH failure. Segmented regression modeling assessed (1) rates of change in TREC levels before and after TCH failure, and (2) whether these were affected by cellular proliferation, which may dilute sjTREC levels. TCH failure was associated with a large decline in sjTREC ( median 1109-fold, p = 0.028); the rate of this decline was only slightly affected when increased proliferation of naive T cells or other peripheral lymphocytes was taken into account. Preferential loss of naive CD4(+) T cells was also noted before TCH failure, as has been seen in other studies. These results suggest that deficits in de novo T cell production, either through the decline of thymic function or the destruction of naive T cells, are likely to play an important role in TCH failure and progression of HIV-1 disease. C1 NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Univ Calif Berkeley, Dept Nutr Sci, Berkeley, CA 94720 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Margolick, JB (reprint author), 615 N Wolfe St,Room E 5153, Baltimore, MD 21205 USA. EM jmargoli@jhsph.edu RI Chattopadhyay, Pratip/B-9227-2008; OI Gange, Stephen/0000-0001-7842-512X; Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999]; NCRR NIH HHS [M01 RR000052, M01-RR00052]; NIAID NIH HHS [AI 35041, AI 42855, U01 AI035039, AI 35039, AI 35042, AI 37984, AI 35043, R01 AI041401, R01 AI042532, U01 AI035041, AI 43866, U01 AI035040, U01 AI037984, AI 35040, AI 42532, AI 41401, R01 AI043866, U01 AI035042, R56 AI042532, R37 AI043866, P30 AI042855]; NIDA NIH HHS [R56 DA004334, DA 04334, R01 DA004334, R37 DA004334] NR 47 TC 17 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2006 VL 22 IS 6 BP 501 EP 507 DI 10.1089/aid.2006.22.501 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 060GA UT WOS:000238789300005 PM 16796525 ER PT J AU von Gegerfelt, AS Alicea, C Valentin, A Morrow, M van Rompay, KKA Ayash-Rashkovsky, M Markham, P Else, JG Marthas, ML Pavlakis, GN Ruprecht, RM Felber, BK AF von Gegerfelt, AS Alicea, C Valentin, A Morrow, M van Rompay, KKA Ayash-Rashkovsky, M Markham, P Else, JG Marthas, ML Pavlakis, GN Ruprecht, RM Felber, BK TI Long lasting control and lack of pathogenicity of the attenuated Rev-independent SIV in rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; CONSTITUTIVE TRANSPORT ELEMENT; IN-VITRO PROPERTIES; REVERSE-TRANSCRIPTASE; POSTTRANSCRIPTIONAL REGULATION; SECONDARY STRUCTURE; RETROVIRUS TYPE-1; MOLECULAR CLONES; ADULT MACAQUES; M184V MUTATION AB A cohort of 22 rhesus macaques of Indian origin infected as neonates, juveniles, or adults by Rev-independent strains of SIV was monitored over several years. After the initial acute phase, virus replication was controlled and plasma virus loads were persistently below the threshold of the assay. The animals were monitored for up to 7.6 years after infection for viral loads, cellular and humoral immune responses, hematological changes, and overall health and no signs of immune dysfunction or AIDS were observed. This study represents several years of additional observation compared to the previously published results, and indicates that the Rev-independent SIV clones tested do not cause AIDS-like progressive disease within 7.6 years from infection. All the animals showed persistent humoral and cellular SIV-specific immune responses, consistent with chronic infection. Different Rev-independent SIV strains showed similar properties and lack of pathogenicity. Multicolor flow cytometric analysis demonstrated preservation of the Central Memory subset of T cells in the attenuated SIV-infected animals. This study demonstrates a potent, long-lasting control of the Rev-independent attenuated SIV in macaques independent of the age at virus exposure. C1 Natl Canc Inst, Canc Res Ctr, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA. NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Adv BioSci Labs Inc, Kensington, MD 20895 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Felber, BK (reprint author), Natl Canc Inst, Canc Res Ctr, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Bldg 535,Room 209, Frederick, MD 21702 USA. EM felber@ncifcrf.gov FU NCRR NIH HHS [RR-00165, RR14180, RR00169] NR 45 TC 5 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN PY 2006 VL 22 IS 6 BP 516 EP 528 PG 13 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 060GA UT WOS:000238789300007 PM 16796527 ER PT J AU Shen, PH Hodgkinson, C Yuan, Q Caycedo, D Newman, E Enoch, MA Xu, K Goldman, D AF Shen, P. -H. Hodgkinson, C. Yuan, Q. Caycedo, D. Newman, E. Enoch, M. -A. Xu, K. Goldman, D. TI Ancestry informative markers for detection of population stratification SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 7A EP 7A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400002 ER PT J AU Enoch, MA Newman, TK Steer, CD Golding, J Goldman, D AF Enoch, M. -A. Newman, T. K. Steer, C. D. Golding, J. Goldman, D. CA ALSPAC Team TI The impact of adverse life events and MAOA genotype on alcoholism vulnerability disorders: A cohort study in 7000 children SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. Univ Bristol, Bristol BS8 1TH, Avon, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 8A EP 8A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400008 ER PT J AU Enoch, MA Schwartz, LS Yuan, Q Albaugh, B Virkkunen, M Goldman, D AF Enoch, M. -A. Schwartz, L. S. Yuan, Q. Albaugh, B. Virkkunen, M. Goldman, D. TI Gene-gene interaction between GABRA2 and GABRB1 in alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. 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 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 8A EP 8A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400007 ER PT J AU Ducci, F Newman, TK Funt, S Virkkunen, M Goldman, D AF Ducci, F. Newman, T. K. Funt, S. Virkkunen, M. Goldman, D. TI Lack of association between a functional polymorphism in the promoter region of MAOA with alcoholism and externalizing disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 9A EP 9A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400010 ER PT J AU Hu, XZ Rush, AJ Chamey, D Wilson, AF Sorant, AJM Panpanicolaou, GJ Fava, M Trivedi, MH Wisniewski, S Laje, G Buervenich, S McMahon, FJ Manji, H Lipsky, RH AF Hu, X-Z. Rush, A. J. Chamey, D. Wilson, A. F. Sorant, A. J. M. Panpanicolaou, G. J. Fava, M. Trivedi, M. H. Wisniewski, S. Laje, G. Buervenich, S. McMahon, F. J. Manji, H. Lipsky, R. H. TI Serotonin transporter promoter polymorphism predicting increased transcription is associated with tolerability to citalopram treatment in the STAR*D effectiveness trial SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Sect Mol Genet, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 9A EP 9A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400012 ER PT J AU Oroszi, G Jeste, N Klein, T Hennig, J Goldman, D Reuter, M AF Oroszi, G. Jeste, N. Klein, T. Hennig, J. Goldman, D. Reuter, M. TI Lack of association of Thr105lle, a functional polymorphism of histamine N-methyltransferase (HNMT), with alcoholism in German Caucasian SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 10A EP 10A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400016 ER PT J AU Xu, K Yuanl, Q Hodgkinson, CA Shen, P Neuhold, L Ren, Z Warren, K Goldman, D AF Xu, K. Yuanl, Q. Hodgkinson, C. A. Shen, P. Neuhold, L. Ren, Z. Warren, K. Goldman, D. TI A large-scale approach for identifying vulnerability genes to alcoholism: A 1536 SNP array SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 11A EP 11A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400020 ER PT J AU Rex, EB Rankin, ML Lovinger, D Sibley, DR AF Rex, E. B. Rankin, M. L. Lovinger, D. Sibley, D. R. TI Ethanol modulation of D1-receptor signaling appears to be mediated by a PKC-dependent mechanism. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Natl Inst Neurol & Disorders & Stroke, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 13A EP 13A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400027 ER PT J AU Honse, Y Lovinger, DM AF Honse, Y. Lovinger, D. M. TI Examination of the role of the NR2A subunit in ethanol effects on NMDAR-mediateid synaptic responses using knockout mice. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LIN, NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 19A EP 19A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400052 ER PT J AU Adermark, L Lovinger, DM AF Adermark, L. Lovinger, D. M. TI Ethanol effects on electrophysiological properties of astrocytes in striatal brain slices SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 22A EP 22A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400063 ER PT J AU Spinelli, S Schwandt, M Erickson, K Lindell, S Schulkin, J Gold, P Suomi, SJ Higley, JD AF Spinelli, S. Schwandt, M. Erickson, K. Lindell, S. Schulkin, J. Gold, P. Suomi, S. J. Higley, J. D. TI Relationship between behavioral and neurochemical changes in rhesus macaques during a separation paradigm SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Poolesville, MD USA. Natl Inst Mental Hlth, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 24A EP 24A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400073 ER PT J AU Sommer, WH Rimondini, R Hansson, AC Heilig, M AF Sommer, W. H. Rimondini, R. Hansson, A. C. Heilig, M. TI CRH signaling and the dark side of addiction: Long lasting hyperreactivity to stress in animals with a history of alcohol dependence SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 28A EP 28A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400086 ER PT J AU Breslow, RA Falk, DE Grummer-Strawn, LM Fein, SB AF Breslow, R. A. Falk, D. E. Grummer-Strawn, L. M. Fein, S. B. TI Alcohol consumption among breastfeeding women. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 49A EP 49A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400173 ER PT J AU Faden, VB Newes-Adeyi, G Chen, C AF Faden, Vivian B. Newes-Adeyi, Gabriella Chen, Chiung TI The relationship of tanner stage, age and drinking in adolescent boys and girls SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Bethesda, MD USA. CSR Inc, Arlington, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 55A EP 55A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400196 ER PT J AU Falk, DE Yi, H AF Falk, D. E. Yi, H. TI Treatment seeking by comorbid individuals with DSM-IV alcohol dependence and mood and anxiety disorders: Results from the national epidemiologic survey on alcohol and related conditions (NESARC) SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 58A EP 58A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400209 ER PT J AU Davis, MI Lovinger, DM AF Davis, Margaret I. Lovinger, David M. TI Transgenic mice expressing gfp under neuronal population-specific promoters for examining the effects of teratogens on neuronal development SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD 20892 USA. RI Davis, Margaret/F-4165-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 64A EP 64A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400233 ER PT J AU Boyce-Rustay, JM Holmes, A AF Boyce-Rustay, J. M. Holmes, A. TI Mice lacking the NMDA receptor NR2A subunit exhibit impaired conditioned reward and enhanced ataxic responses to ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 67A EP 67A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400242 ER PT J AU Gawrisch, K Koenig, B AF Gawrisch, Klaus Koenig, Bernd TI A high resolution NMR study of ethanol binding to bicelles implications for ethanol detection by MRI SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Res Ctr Julich, Inst Biol Struct, D-52425 Julich, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 73A EP 73A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400266 ER PT J AU Sun, H Zhang, L AF Sun, Hui Zhang, Li TI Distinct molecular processes mediate the potentiating effects induced by Delta 9-tetrahydrocannabinol and ethanol on glycine alpha 1 receptors expressed in xenopus oocytes. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 78A EP 78A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400288 ER PT J AU Wang, Y Tsai, YL Hoffer, BJ AF Wang, Y. Tsai, Y. L. Hoffer, B. J. TI Ethanol antagonizes NMDA-mediated hypertension and nitric oxide production in the rostral ventrolateral medullar of adult rats. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 79A EP 79A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400290 ER PT J AU Ramchandani, VA Saxena, NA Carroll, M Hoofer, ME Spero, DE Walker, JT Hommer, D AF Ramchandani, V. A. Saxena, N. A. Carroll, M. Hoofer, M. E. Spero, D. E. Walker, J. T. Hommer, D. TI Gender differences in subjective effects of alcohol when breath alcohol concentrations are clamped at 50mg%. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 91A EP 91A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400338 ER PT J AU Krystal, JH Madonick, S Perry, E Gueorguieva, R Brush, L Wray, Y Belger, A D'Souza, DC AF Krystal, J. H. Madonick, S. Perry, E. Gueorguieva, R. Brush, L. Wray, Y. Belger, A. D'Souza, D. C. TI Potentiation of low dose ketamine effects by naltrexone: Potential implications for the pharmacotherapy of alcoholism. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Yale Univ, Sch Med, NIAAA, Ctr Translat Neurosci Alcholism, West Haven, CT 06516 USA. VA Connecticut Healthcare Syst, VA Alcohol Res Ctr, West Haven, CT 06516 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 104A EP 104A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400391 ER PT J AU Harford, TC Yi, H Faden, VB AF Harford, T. C. Yi, H. Faden, V. B. TI The dimensionality of DSM-IV alcohol use disorders among adolescent and young adult drinkers aged 12-25 and symptom reporting bias by gender, age, and race/ethnicity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 CSR Inc, NIAAA, Alcohol Epidemiol Data Syst, NIH, Arlington, VA 22201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 110A EP 110A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400417 ER PT J AU Barr, CS Gupte, M Newman, TK Lipsky, R Heilig, M Goldman, D Higley, JD AF Barr, C. S. Gupte, M. Newman, T. K. Lipsky, R. Heilig, M. Goldman, D. Higley, J. D. TI Association of a CRH gene haplotype with alcohol consumption in rhesus macaques SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, NIH, Lab Clin & Translat Studies, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 119A EP 119A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400452 ER PT J AU Lindell, SG Barr, CS Suomi, SJ Goldman, D Heilig, M Higley, JD AF Lindell, S. G. Barr, C. S. Suomi, S. J. Goldman, D. Heilig, M. Higley, J. D. TI Variation in the rhnpy promoter region is associated with differences in CSF levels of NPY and alcohol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LCTS, NIH, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 120A EP 120A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400454 ER PT J AU Newman, TK Wendland, JR Barr, CS Kruse, M Gallager, P Higley, JD Goldman, D AF Newman, T. K. Wendland, J. R. Barr, C. S. Kruse, M. Gallager, P. Higley, J. D. Goldman, D. TI Multiple novel polymorphisms in the rhesus macaque DRD4 and TPH2 genes: Association with impulsive and aggressive behavior SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 120A EP 120A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400455 ER PT J AU Hansson, AC Cippitelli, A Sommer, WH Bjoerk, K Terasmaa, A Fideli, A Massi, M Heilig, M Ciccocioppo, R AF Hansson, A. C. Cippitelli, A. Sommer, W. H. Bjoerk, K. Terasmaa, A. Fideli, A. Massi, M. Heilig, M. Ciccocioppo, R. TI Interaction between corticotropin-releasing hormone 1 receptor gene polymorphism and expression with environmental stress in relapse to alcohol seeking behavior by rats selected for high ethanol preference SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, I-62032 Bethesda, MD USA. Univ Camerino, Dept Exp Med & Publ Hlth, Camerino, Italy. RI Terasmaa, Anton/I-3312-2015 OI Terasmaa, Anton/0000-0002-5139-1764 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 127A EP 127A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400482 ER PT J AU Thanos, PK Michaelides, M Wang, GJ Volkow, ND AF Thanos, Panayotis (Peter) K. Michaelides, Michael Wang, Gene Jack Volkow, Nora D. TI Effects of the cannabinoid CB1 antagonist SR141716 on food intake and ethanol consumption in lean and obese Zucker rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol & Neuroimaging Lab, Upton, NY 11973 USA. NIAAA, Lab Neuroimaging, Bethesda, MD 20892 USA. RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 130A EP 130A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400493 ER PT J AU Bjork, K Sommer, WH Rimondini, R Hansson, AC Hyytia, P Lefkowitz, RJ Heilig, M AF Bjork, K. Sommer, W. H. Rimondini, R. Hansson, A. C. Hyytia, P. Lefkowitz, R. J. Heilig, M. TI A role for beta-arrestin 2 in mediating the rewarding properties of ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Natl Publ Hlth Inst, Helsinki, Finland. RI Rimondini, Roberto/B-2500-2010 OI Rimondini, Roberto/0000-0003-4099-513X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 134A EP 134A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400511 ER PT J AU Thorsell, A Johnson, J Kunos, G Heilig, M AF Thorsell, A. Johnson, J. Kunos, G. Heilig, M. TI Effect of an adenosine A2a receptor antagonist on alcohol consumption and related behaviors in Wistar rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 137A EP 137A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299400521 ER PT J AU Pittman, B Gueorguieva, R Krupitsky, E Rudenko, A Krystal, JH AF Pittman, B. Gueorguieva, R. Krupitsky, E. Rudenko, A. Krystal, J. H. TI Multidimensionality of the Alcohol Withdrawal Symptom Checklist: A factor analysis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Yale Univ, Sch Med, NIAAA, Ctr Translat Neurostience Alcoholism, New Haven, CT 06508 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 161A EP 161A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401066 ER PT J AU Harford, TC Grant, BF Yi, H AF Harford, T. C. Grant, B. F. Yi, H. TI The association between conduct disorders with and without antisocial behavior disorders and DSM-IV alcohol use disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, CSR Inc, NIH, Arlington, VA 22201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 165A EP 165A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401084 ER PT J AU Moss, HB Chen, CM Yi, H AF Moss, H. B. Chen, C. M. Yi, H. TI Empirical subtyping of alcohol dependence in a nationally representative sample: A latent class analysis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 166A EP 166A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401087 ER PT J AU Chen, CM Yi, H Sorensen, RG AF Chen, C. M. Yi, H. Sorensen, R. G. TI Drinking and risks for bone fractures SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, NIH, CSR Inc, Arlington, VA 22201 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 167A EP 167A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401091 ER PT J AU Yoon, YH Yi, HY AF Yoon, Y. -H. Yi, H. -Y. TI Liver cirrhosis and viral Hepatitis C infection mortality among Hispanic subgroups in the United States, 1999-2003: A multiple cause analysis. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Alcohol Epidemiol Data Syst, CSR Inc, NIH, Arlington, VA 22201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 168A EP 168A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401094 ER PT J AU Chen, SA Flint, WW Iba, KE Suomi, SJ Higley, JD AF Chen, S. A. Flint, W. W. Iba, K. E. Suomi, S. J. Higley, J. D. TI Social drinking in female rhesus macaques: A profile of voluntary oral ethanol consumption, rearing history, and dominance ranking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LCTS, Sect Study Primate Models Psychopathol, Anim Ctr,NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 188A EP 188A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401173 ER PT J AU Hommer, DW Momenan, R Kerich, M Israel, E AF Hommer, D. W. Momenan, R. Kerich, M. Israel, E. TI NEO personality domain of conscientiousness predicts frontal lobe volume in young alcoholic males SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 192A EP 192A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401189 ER PT J AU Walker, JT Hommer, D Momenan, R Rawlings, R Heilig, M AF Walker, J. T. Hommer, D. Momenan, R. Rawlings, R. Heilig, M. TI Brain volume shrinkage and common lab values in alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LCTS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 193A EP 193A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401193 ER PT J AU Salloum, JB Ramchandani, VA Skora, D Saxena, N Hommer, DW AF Salloum, J. B. Ramchandani, V. A. Skora, D. Saxena, N. Hommer, D. W. TI Examination of neural activation and subjective perceptions of ethanol effects: An ethanol infusion study in healthy volunteers using fMRI SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 194A EP 194A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401198 ER PT J AU Walker, JT Hommer, D Momenan, R Rawlings, R Heilig, M AF Walker, J. T. Hommer, D. Momenan, R. Rawlings, R. Heilig, M. TI Serum magnesium predicts brain shrinkage in alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LCTS, I&E, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 217A EP 217A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401292 ER PT J AU Horiguchi, N Gao, B AF Horiguchi, Norio Gao, Bin TI Activation of signal transducer and activator of transcription 3 (STAT3) in end-stage of alcoholic and hepatitis C cirrhosis: Suppression by alcohol consumption SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 221A EP 221A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401308 ER PT J AU Jeong, WI Gao, B AF Jeong, W. I. Gao, B. TI Chronic ethanol consumption abrogates the antifibrotic effect of NK/IFN-gamma/STAT1 in the liver SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Sect Liver Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 222A EP 222A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401309 ER PT J AU Moon, KH Hood, BL Kim, BJ Conrads, TP Veenstra, TD Song, BJ AF Moon, K. H. Hood, B. L. Kim, B. J. Conrads, T. P. Veenstra, T. D. Song, B. J. TI Inactivation of oxidized and S-nitrosylated mitochondrial proteins in alcohol-exposed rat liver SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Memb Biochem Biophys, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 223A EP 223A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401314 ER PT J AU Enoch, MA Schwartz, LS Waheed, J Harris, CR Albaugh, B Virkkunen, M Goldman, D AF Enoch, M. -A. Schwartz, L. S. Waheed, J. Harris, C. R. Albaugh, B. Virkkunen, M. Goldman, D. TI Linkage of two GABAA receptor genes and COMT Val158Met to alcoholism and smoking in Finnish Caucasians and plains American Indians; Sexually dimorphic effects SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 235A EP 235A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401359 ER PT J AU Goldman, D Hodgkinson, C Xu, K Shen, P Yuan, Q Robin, R Albaugh, B Enoch, MA AF Goldman, D. Hodgkinson, C. Xu, K. Shen, P. Yuan, Q. Robin, R. Albaugh, B. Enoch, M. A. TI Linkage of alcoholism in American Indian populations: Integrating results from whole-genome linkage SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Lab Neurogenet, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 235A EP 235A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401361 ER PT J AU Gao, B AF Gao, Bin TI Proteasome, the JAK-STAT signaling pathway, and alcoholic liver disease SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 243A EP 243A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401391 ER PT J AU Lupica, CR Riegel, AC AF Lupica, C. R. Riegel, A. C. TI Activity-dependent endocannabinoid release from midbrain DA neurons. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIDA Intramural Res Program, Electrophysiol Sect, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 245A EP 245A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401402 ER PT J AU Ciccocioppo, R Economidou, D Cippitelli, A Weiss, F Heilig, M Massi, M AF Ciccocioppo, R. Economidou, Daina Cippitelli, Andrea Weiss, Friedbert Heilig, Markus Massi, M. TI The nociceptin/orphanin FQ system as at target for the treatment of alcohol abuse. Evidence from preclinical research. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 Univ Camerino, Dept Expt Med & Publ Hlth, Camerino, Italy. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 254A EP 254A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401437 ER PT J AU Heilig, M Hansson, C Cippitelli, A Sommer, WH Fideli, A Massi, M Ciccocioppo, R AF Heilig, M. Hansson, C. Cippitelli, A. Sommer, W. H. Fideli, A. Massi, M. Ciccocioppo, R. TI Validation of CRH1 receptors as a treatment target in alcohol dependence using alcohol preferring msP rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, LCTS, Bethesda, MD 20892 USA. Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 254A EP 254A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401436 ER PT J AU Hilton, M AF Hilton, M. TI Barriers to wider use of pharmacotherapy in clinical practice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Div Epidemiol & Prevent, Rockville, MD 20852 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 257A EP 257A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401450 ER PT J AU Mattson, ME AF Mattson, M. E. TI Background and rationale for the COMBINE Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, DHHS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 260A EP 260A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401459 ER PT J AU Thorsell, A Ehlers, CL Koob, GF Heilig, M AF Thorsell, A. Ehlers, C. L. Koob, G. F. Heilig, M. TI Neuropeptide Y in regulation of ethanol intake: Effects of NPY administration in animals with a history of ethanol exposure. SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-29, 2006 CL Baltimore, MD SP Res Soc Alcoholism C1 NIAAA, Sect Mol Pathophysiol, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA USA. RI koob, george/P-8791-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 SU S BP 280A EP 280A PG 1 WC Substance Abuse SC Substance Abuse GA 053IS UT WOS:000238299401543 ER PT J AU Faden, VB AF Faden, VB TI Trends in initiation of alcohol use in the united states 1975 to 2003 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE initiation; trends; youth; alcohol ID SELF-REPORTED AGE; PROJECT NORTHLAND; RISK-FACTORS; OF-ONSET; DRUG-USE; DRINKING; ADOLESCENTS; RELIABILITY; INVOLVEMENT; STUDENTS AB Alcohol is the drug of choice for youth in the United States. By 8th grade, more than 40% of youth have used alcohol; by 12th grade, almost 80% have done so (MTF, 2003). And many of these young people begin drinking at relatively early ages. On average, boys start drinking earlier than girls, and whites and Native Americans start drinking earlier than youth of other race/ethnicities. As alcohol consumption is such a high prevalence behavior among young people, it is crucial to understand the initiation of drinking as well as possible, so as to facilitate and inform interventions to delay this behavior. One facet of this involves investigating trends in the initiation of drinking. Multiple years of data from 3 national surveys, Monitoring the Future (MTF)-1975 to 2003 for 12th graders, 1993 to 2003 for 8th and 10th graders; the National Household Survey on Drug Abuse (NHSDA) [now called the National Survey on Drug Use and Health (NSDUH)]-1991 to 1998; and the Youth Risk Behavior Surveillance System (YRBSS)-1991 to 2003, were analyzed using joinpoint analysis to further understanding of trends in the initiation of drinking by youth. The present analysis examines whether the age of drinking initiation has changed over time and evaluates trends in the percentages of youth who start drinking by various grades. Simultaneous examination of data from the 3 surveys indicates that 7th and 8th grades (when most youth are 13-14) are peak years for the initiation of drinking. Further, the present analysis shows that although the percentage of youth who start drinking early (before age 13) has declined (YRBSS, MTF), the average age of initiation of drinking for these "very early starters" did not change over the period 1991 to 1998 (NHSDA/NSDUH). At the same time, an upward shift in the "normative" age of initiation has occurred (NHSDA/NSDUH, MTF). Results of analyses by gender and race/ethnicity indicate similar trends over time. A more nuanced understanding of the initiation of drinking can have important implications for prevention. C1 NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Faden, VB (reprint author), NIAAA, Div Epidemiol & Prevent Res, NIH, 6000 Execut Blvd,MSC 7003,Suie 514, Bethesda, MD 20892 USA. EM vfaden@mail.nih.gov NR 30 TC 56 Z9 57 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 BP 1011 EP 1022 DI 10.1111/j.1530-0277.2006.00115.x PG 12 WC Substance Abuse SC Substance Abuse GA 046KQ UT WOS:000237810900014 PM 16737460 ER PT J AU Venner, KL Matzger, H Forcehimes, AA Moos, RH Feldstein, SW Willenbring, ML Weisner, C AF Venner, KL Matzger, H Forcehimes, AA Moos, RH Feldstein, SW Willenbring, ML Weisner, C TI Course of recovery from alcoholism SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE recovery; alcohol dependence; social context ID FOLLOW-UP; SUBSTANCE-ABUSE; UNITED-STATES; UNTREATED INDIVIDUALS; THERAPEUTIC ALLIANCE; DRINKING BEHAVIOR; NATURAL RECOVERY; PROBLEM DRINKERS; SOCIAL NETWORKS; TREATMENT TRIAL AB This article represents the proceedings of a symposium at the 2005 Research Society on Alcoholism meeting in Santa Barbara, California, organized and chaired by Kamilla L. Venner. This symposium integrated current empirical research on the course of recovery from alcoholism from multiple perspectives, an aim that is consistent with NIAAA's new focus on the process of recovery. The presentations and presenters were as follows: (1) The Role of Community Services and Informal Support on 7-Year Drinking Outcomes in Treated and Untreated Drinkers, by Helen Matzger; (2) The Sequence of Recovery Events in a Native American Sample, by Kamilla L. Venner; (3) Transformational Change in Recovery, by Alyssa A. Forcehimes; (4) Social Settings and Substance Use: Contextual Factors in Recovery, by Rudolf H. Moos; and (5) A Broader View of Change in Drinking Behavior, by discussant Mark L. Willenbring. A theme connecting the presentations was that treatment is but one discrete aspect to recovery and that sustained recovery is often influenced by an individual interaction with others within a social context. Collectively, presentations underscored the need to think more broadly about factors contributing to the remission of alcohol dependence. C1 Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87106 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Inst Publ Hlth, Alcohol Res Grp, Berkeley, CA USA. Ctr Hlth Care Evaluat, Vet Affairs Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Palo Alto, CA 94304 USA. NIAAA, Bethesda, MD USA. Kaiser No Calif Div Res, Oakland, CA USA. RP Venner, KL (reprint author), Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, 1 Univ New Mexico,MSC11 6280, Albuquerque, NM 87106 USA. EM kamilla@unm.edu FU NIAAA NIH HHS [K23 AA014207, R01 AA009750, R01 AA09750, P050 AA05595, R01 AA012718, R01 AA015685, U01 AA014926, AA12718, P50 AA005595, K23 AA014207-05, AA15685] NR 86 TC 7 Z9 7 U1 3 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2006 VL 30 IS 6 BP 1079 EP 1090 DI 10.1111/j.1530-0277.2006.00121.x PG 12 WC Substance Abuse SC Substance Abuse GA 046KQ UT WOS:000237810900022 PM 16737468 ER PT J AU Kelemen, LE Cerhan, JR Lim, U Davis, S Cozen, W Schenk, M Colt, J Hartge, P Ward, MH AF Kelemen, LE Cerhan, JR Lim, U Davis, S Cozen, W Schenk, M Colt, J Hartge, P Ward, MH TI Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin lymphoma: a National Cancer Institute-Surveillance, Epidemiology, and End Results population-based case-control study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE anticarcinogenic agents; cruciferous vegetables; carotenoids; diet; neoplasms; zinc ID VITAMIN SUPPLEMENT USE; TOTAL-ENERGY-INTAKE; DIETARY FACTORS; BREAST-CANCER; UNITED-STATES; MEAT-COOKING; DNA-DAMAGE; WOMEN; QUESTIONNAIRE; HEALTH AB Background: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin lymphoma (NHL). Objective: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities. Design: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institute-sponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (< 65 y) and from Medicare files ( 65 y), were matched to cases by age, center, race, and sex. Of 1321 case and 1057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% Cls. Results: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% Cl: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36,0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% Cl: 0.39, 1.00; Pfor trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% Cl: 0.36,0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients. Conclusion: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk. C1 Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Univ So Calif, Los Angeles, CA 90089 USA. Karmanos Canc Inst, Detroit, MI USA. RP Cerhan, JR (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St Sw, Rochester, MN 55905 USA. EM cerhan.james@mayo.edu FU Intramural NIH HHS; NCI NIH HHS [R25 CA92049-03, N01-CP-65064, N01-CP-67009, N02-PC-71105, N01-CP-67010, R25 CA092049, N01-PC-67008] NR 53 TC 46 Z9 46 U1 2 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2006 VL 83 IS 6 BP 1401 EP 1410 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 054IL UT WOS:000238369900025 PM 16762953 ER PT J AU Hibbeln, JR Nieminen, LRG Blasbalg, TL Riggs, JA Lands, WEM AF Hibbeln, JR Nieminen, LRG Blasbalg, TL Riggs, JA Lands, WEM TI Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on n-3 Fatty Acids - Recommendations for Therapeutics and Prevention CY MAY 21, 2005 CL Columbia Univ, Inst Human Nutr, New York, NY HO Columbia Univ, Inst Human Nutr DE n-3 fatty acids; Dietary Reference Intake; Adequate Intake; Recommended Dietary Allowance; docosahexaenoic acid; eicosapentaenoic acid; arachidonic acid; linoleic acid; dose-response study; omega-3 fatty acids ID PLACEBO-CONTROLLED TRIAL; PRELIMINARY DOUBLE-BLIND; SEAFOOD CONSUMPTION; LINOLEIC-ACID; CARDIOVASCULAR-DISEASE; DEPRESSIVE DISORDER; ECOLOGICAL ANALYSIS; MAJOR DEPRESSION; FISH CONSUMPTION; RISK-FACTORS AB Background: The worldwide diversity of dietary intakes of n-6 and n-3 fatty acids influences tissue compositions of n-3 long-chain fatty acids (LCFAs: eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) and risks of cardiovascular and mental illnesses. Objective: We aimed to estimate healthy dietary allowances for n-3 LCFAs that would meet the nutrient requirements of 97-98% of the population. Design: Deficiency in n-3 LCFAs was defined as attributable risk from 13 morbidity and mortality outcomes, including all causes, coronary heart disease, stroke, cardiovascular disease, homicide, bipolar disorder, and major and postpartum depressions. Dietary availability of n-3 LCFAs from commodities for 38 countries and tissue composition data were correlated by best fit to each illness in deficiency risk models. Results: The potential attributable burden of disease ranged from 20.8% (all-cause mortality in men) to 99.9% (bipolar disorder). n-3 LCFA intake for Japan (0.37% of energy, or 750 mg/d) met criteria for uniformly protecting > 98% of the populations worldwide. n-3 LCFA intakes needed to meet a tissue target representative of Japan (60% n-3 in LCFA) ranged from 278 mg/d (Philippines, with intakes of 0.8% of energy as linoleate, 0.08% of energy as a-linolenate, and 0.06% of energy as arachidonic acid) to 3667 mg/d (United States, with 8.91% of energy as linoleate, 1.06% of energy as alpha-linolenate, and 0.08% of energy as arachidonic acid). Conclusions: With caveats inherent for ecologic, nutrient disappearance analyses, a healthy dietary allowance for n-3 LCFAs for current US diets was estimated at 3.5 g/d for a 2000-kcal diet. This allowance for n-3 LCFAs can likely be reduced to one-tenth of that amount by consuming fewer n-6 fats. C1 NIAAA, LMBB, NIH, Bethesda, MD 20892 USA. NIH, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Hibbeln, JR (reprint author), NIAAA, LMBB, NIH, 31 Center Dr 1B58 MSC2088, Bethesda, MD 20892 USA. EM jhibbeln@mail.nih.gov FU Intramural NIH HHS NR 58 TC 225 Z9 237 U1 2 U2 35 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2006 VL 83 IS 6 SU S BP 1483S EP 1493S PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 055UY UT WOS:000238477300006 PM 16841858 ER PT J AU Lugassy, C Vernon, SE Busam, K Engbring, JA Welch, DR Poulos, EG Kleinman, HK Barnhill, RL AF Lugassy, Claire Vernon, Stephen E. Busam, Klaus Engbring, Jean A. Welch, Danny R. Poulos, Evangelos G. Kleinman, Hynda K. Barnhill, Raymond L. TI Angiotropism of human melanoma: Studies involving in transit and other cutaneous metastases and the chicken chorioallantoic membrane - Implications for extravascular melanoma invasion and metastasis SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE angiotropism; extravascular migratory metistasis (EVMM); in transit melanoma metastases; chick chorioallantoic membrane (CAM); human melanoma cells ID MALIGNANT-MELANOMA; MIGRATORY METASTASIS; IMMUNOHISTOCHEMICAL OBSERVATIONS; PERINEURAL INVASION; CELL-MIGRATION; TUMOR; LAMININ; MATRIX; SPREAD; CANCER AB Melanoma cell migration along the Outside of vessels has been termed "extravascular migratory metastasis" (EVMM), as distinct from intravascular dissemination. Previous studies in both human and experimental melanoma models have shown angiotropism of melanoma cells, suggesting EVMM. Our objectives are to study the mechanism of dissemination of human melanoma cells in the chick chorioallantoic membrane (CAM) and to compare the histopathology in the CAM with that of patients with in transit and other cutaneous melanoma metastases. Human and murine melanoma cells were inoculated onto the CAM and observed over a 10-day period for tumor dissemination. Both human melanoma specimens from 26 patients and melanoma cells growing on the CAM showed the presence of tumor cell angiotropism at the invasive front of the turner and at some distance from the tumor mass. In addition, a clear progression of melanoma cells spreading on the CAM was observed along the abluminal surface of vessels, where they occupied a perivascular location. By day 10 after injection, small micrometastases had developed along vessels, in a pattern similar to that in transit and other cutaneous melanoma metastases. In addition, the results suggested that the number of micrometastases directly correlated with increasing tumor volume. Taken together, these data suggest that the CAM is a relevant model for studying tumor cell dissemination, and that EVMM may be a mechanism by which some melanoma cells spread to nearby and even distant sites. C1 Univ Miami, Jackson Mem Hosp, Sch Med, Dept Pathol, Miami, FL 33136 USA. Univ Miami, Jackson Mem Hosp, Sch Med, Dept Dermatol, Miami, FL 33136 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Natl Inst dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Barnhill, RL (reprint author), Univ Miami, Jackson Mem Hosp, Sch Med, Dept Pathol, Miami, FL 33136 USA. EM rbarnhill@med.miami.edu RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [R01 CA087728] NR 31 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD JUN PY 2006 VL 28 IS 3 BP 187 EP 193 DI 10.1097/00000372-200606000-00001 PG 7 WC Dermatology SC Dermatology GA 095EN UT WOS:000241291100001 PM 16778482 ER PT J AU Smith-Warner, SA Spiegelman, D Ritz, J Albanes, D Beeson, WL Bernstein, L Berrino, F van den Brandt, PA Buring, JE Cho, E Colditz, GA Folsom, AR Freudenheim, JL Giovannucci, E Goldbohm, RA Graham, S Harnack, L Horn-Ross, PL Krogh, V Leitzmann, MF McCullough, ML Miller, AB Rodriguez, C Rohan, TE Schatzkin, A Shore, R Virtanen, M Willett, WC Wolk, A Zeleniuch-Jacquotte, A Zhang, SMM Hunter, DJ AF Smith-Warner, Stephanie A. Spiegelman, Donna Ritz, John Albanes, Demetrius Beeson, W. Lawrence Bernstein, Leslie Berrino, Franco van den Brandt, Piet A. Buring, Julie E. Cho, Eunyoung Colditz, Graham A. Folsom, Aaron R. Freudenheim, Jo L. Giovannucci, Edward Goldbohm, R. Alexandra Graham, Saxon Harnack, Lisa Horn-Ross, Pamela L. Krogh, Vittorio Leitzmann, Michael F. McCullough, Marjorie L. Miller, Anthony B. Rodriguez, Carmen Rohan, Thomas E. Schatzkin, Arthur Shore, Roy Virtanen, Mikko Willett, Walter C. Wolk, Alicja Zeleniuch-Jacquotte, Anne Zhang, Shumin M. Hunter, David J. TI Methods for pooling results of epidemiologic studies - The pooling project of prospective studies of diet and cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; diet; epidemiologic methods; meta-analysis; neoplasms ID FOOD FREQUENCY QUESTIONNAIRE; MEASUREMENT ERROR-CORRECTION; POOLED ANALYSIS; BREAST-CANCER; COLORECTAL-CANCER; LUNG-CANCER; OVARIAN-CANCER; PROSPECTIVE COHORT; REGRESSION-MODELS; WOMENS HEALTH AB With the growing number of epidemiologic publications on the relation between dietary factors and cancer risk, pooled analyses that summarize results from multiple studies are becoming more common. Here, the authors describe the methods being used to summarize data on diet-cancer associations within the ongoing Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the Pooling Project, the primary data from prospective cohort studies meeting prespecified inclusion criteria are analyzed using standardized criteria for modeling of exposure, confounding, and outcome variables. In addition to evaluating main exposure-disease associations, analyses are also conducted to evaluate whether exposure-disease associations are modified by other dietary and nondietary factors or vary among population subgroups or particular cancer subtypes. Study-specific relative risks are calculated using the Cox proportional hazards model and then pooled using a random- or mixed-effects model. The study-specific estimates are weighted by the inverse of their variances in forming summary estimates. Most of the methods used in the Pooling Project may be adapted for examining associations with dietary and nondietary factors in pooled analyses of case-control studies or case-control and cohort studies combined. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NCI, Nutr Epidemiol Branch, Bethesda, MD USA. Loma Linda Univ, Sch Med, Ctr Hlth Res, Loma Linda, CA 92350 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. NCI, Epidemiol Unit, Milan, Italy. Maastricht Univ, Fac Hlth Sci, Dept Epidemiol, Maastricht, Netherlands. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY USA. TNO Qual Life, Dept Epidemiol, Zeist, Netherlands. No Calif Canc Ctr, Fremont, CA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Amer Canc Soc, Epidemiol & Surveilliance Res, Atlanta, GA USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. RP Smith-Warner, SA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM pooling@hsphsun2.harvard.edu RI Albanes, Demetrius/B-9749-2015; Krogh, Vittorio/K-2628-2016; Colditz, Graham/A-3963-2009; OI Krogh, Vittorio/0000-0003-0122-8624; Colditz, Graham/0000-0002-7307-0291; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [CA55075, CA78548, R01 CA077398] NR 86 TC 138 Z9 139 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 BP 1053 EP 1064 DI 10.1093/aje/kwj127 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 049XT UT WOS:000238051800012 PM 16624970 ER PT J AU Adams, KF Schatzkin, A Harris, TB Kipnis, V Mouw, T Hollenbeck, A Leitzmann, MF AF Adams, K. F. Schatzkin, A. Harris, T. B. Kipnis, V. Mouw, T. Hollenbeck, A. Leitzmann, M. F. CA NIH-AARP Diet Hlth Study TI Overweight, obesity, and mortality in the NIH-AARP diet and health study cohort. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S43 EP S43 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900170 ER PT J AU Ahn, J Moslehi, R Weinstein, S Snyder, K Virtamo, J Albanes, D AF Ahn, J. Moslehi, R. Weinstein, S. Snyder, K. Virtamo, J. Albanes, D. TI Family history of prostate cancer, body size, and prostate cancer risk. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S112 EP S112 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900449 ER PT J AU Alavanja, MCR Coble, J Beane-Freeman, LE Mahajan, R Lubin, J Lynch, CF Knott, C Hoppin, JA Thomas, K Allen, R Hines, CJ Sandler, DA Blair, A AF Alavanja, M. C. R. Coble, J. Beane-Freeman, L. E. Mahajan, R. Lubin, J. Lynch, C. F. Knott, C. Hoppin, J. A. Thomas, K. Allen, R. Hines, C. J. Sandler, D. A. Blair, A. TI Use of agricultural pesticides and prostate cancer risk in the agricultural health study cohort and future plans for molecular studies. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S113 EP S113 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900450 ER PT J AU Basso, O Rasmussen, S Weinberg, CR Wilcox, AJ Irgens, L Skjaerven, R AF Basso, O. Rasmussen, S. Weinberg, C. R. Wilcox, A. J. Irgens, L. Skjaerven, R. TI Time trends in fetal and infant survival in babies of preeclamptic pregnancies. Norway, 1967-2003. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, Epidemiol Branch, DHHS, NIH, Res Triangle Pk, NC USA. NIEHS, Biostat Branch, DHHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S236 EP S236 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901421 ER PT J AU Brotman, RM AF Brotman, R. M. CA FLORA study grp TI Longitudinal patterns of vaginal douching among women in Alabama. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, Flora Study Grp, Rockville, MD 20852 USA. RI Brotman, Rebecca/H-5442-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S147 EP S147 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901067 ER PT J AU Cabana, MD Hediger, ML AF Cabana, M. D. Hediger, M. L. TI Insights from the epidemiology of asthma: Population-based approaches to prevention of the disease. I. Recent insights from the epidemiology of asthma. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, DESPR, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S79 EP S79 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900315 ER PT J AU Carreon, T Ruder, AM Waters, MA Butler, MA Yeager, M Welch, R Chanock, S Schulte, PA AF Carreon, T. Ruder, A. M. Waters, M. A. Butler, M. A. Yeager, M. Welch, R. Chanock, S. Schulte, P. A. TI Lead exposure and glioma among rural residents: The upper midwest health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIOSH, Cincinnati, OH 45226 USA. NCI, Gaithersburg, MD USA. RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S251 EP S251 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901481 ER PT J AU Chang, SC Lacey, JV Brinton, L Hartge, P Adams, K Mouw, T Carroll, L Hollenbeck, A Schatzkin, A Leitzmann, MF AF Chang, S. C. Lacey, J. V., Jr. Brinton, L. Hartge, P. Adams, K. Mouw, T. Carroll, L. Hollenbeck, A. Schatzkin, A. Leitzmann, M. F. TI Body size, weight gain, and postmenopausal endometrial cancer risk in the NIH-AARP diet and health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S40 EP S40 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900158 ER PT J AU Chatterjee, N AF Chatterjee, N. TI Analysis of case-control studies in genetic epidemiology: Classic logistic regression and some novel alternatives. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S170 EP S170 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901159 ER PT J AU Chen, A Dietrich, K Radcliffe, J Rogan, WJ AF Chen, A. Dietrich, K. Radcliffe, J. Rogan, W. J. TI Lead exposure and behavior in urban 7 year olds: Does lead affect behavior through IQ? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Natl Inst Environm Hlth Sci, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S18 EP S18 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900070 ER PT J AU Chodick, G Shalev, V Goren, I Inskip, PD AF Chodick, G. Shalev, V. Goren, I. Inskip, P. D. TI Seasonality in birth weight in Israel; New evidence suggests several global patterns. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S56 EP S56 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900223 ER PT J AU Chodick, G Freedman, DM Kwok, R Fears, T Linet, M Kleinerman, R AF Chodick, G. Freedman, D. M. Kwok, R. Fears, T. Linet, M. Kleinerman, R. TI Improving questionnaire-based assessment of ultraviolet radiation from sunlight: Agreement between daily diary and recalled time outdoors 6 months later. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S29 EP S29 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900117 ER PT J AU Cooney, M Sun, W Louis, GMB AF Cooney, M. Sun, W. Louis, G. M. B. TI Time to pregnancy and secondary sex ratio. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S75 EP S75 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900301 ER PT J AU Devesa, S Anderson, W AF Devesa, S. Anderson, W. TI Colorectal cancer incidence rates by subsite and gender among Asian and white Americans, SEERS 11 areas, 1992-2003. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S106 EP S106 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900423 ER PT J AU Garcia, A Patel, K Guralnik, J AF Garcia, A. Patel, K. Guralnik, J. TI Regional disparities in seatbelt use among American Indians/Alaska natives. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S140 EP S140 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901037 ER PT J AU Gaudet, MM Egan, KM Newcomb, PA Brinton, LA Titus-Ernstoff, L Chanock, SJ Welch, R Trentham-Dietz, A Garcia-Closas, M AF Gaudet, M. M. Egan, K. M. Newcomb, P. A. Brinton, L. A. Titus-Ernstoff, L. Chanock, S. J. Welch, R. Trentham-Dietz, A. Garcia-Closas, M. TI Genetic variation of tumor necrosis factor-alpha (TNF) and risk of breast cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, DCEG, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S128 EP S128 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900510 ER PT J AU Goedert, JJ AF Goedert, J. J. TI Associations of infections and cancers. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S165 EP S165 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901137 ER PT J AU Herrell, R Wyatt, R Sherman-Elvy, E Henter, I Bartko, J Gottesman, I Merikangas, K AF Herrell, R. Wyatt, R. Sherman-Elvy, E. Henter, I. Bartko, J. Gottesman, I. Merikangas, K. TI All-cause and suicide mortality in discharged US military personnel with severe psychiatric disorders. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIMH, Sect Dev Genet Epidemiol, NIH, Bethesda, MD 20892 USA. RI G, I/D-8042-2011; Gottesman, Irving/B-9303-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S238 EP S238 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901430 ER PT J AU Hoffman, HJ Ko, CW Themann, CL Dillon, CF Franks, JR AF Hoffman, H. J. Ko, C-W Themann, C. L. Dillon, C. F. Franks, J. R. TI Reducing noise-induced hearing loss (NIHL) to achieve us healthy people 2010 goals. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Natl Inst Deafness & Other Commun, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S122 EP S122 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900487 ER PT J AU Hoppin, JA Umbach, DM London, SJ Henneberger, PK Kullman, GJ Alavanja, MCR Sandler, DP AF Hoppin, J. A. Umbach, D. M. London, S. J. Henneberger, P. K. Kullman, G. J. Alavanja, M. C. R. Sandler, D. P. TI Pesticide exposure and allergic and nonallergic asthma among farm women in the agricultural health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S157 EP S157 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901107 ER PT J AU Howard, R Gilbert, E Hall, P Storm, H Pukkala, E Langmark, F Travis, L AF Howard, R. Gilbert, E. Hall, P. Storm, H. Pukkala, E. Langmark, F. Travis, L. TI Leukemia following breast cancer: An international population-based study of 376,825 women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S99 EP S99 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900394 ER PT J AU Ji, BT Shu, XO Yang, G Dai, Q Gao, YT AF Ji, B-T Shu, X-O Yang, G. Dai, Q. Gao, Y-T TI Reproductive factors, oral contraceptive use, and colorectal cancer risk in Chinese women. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S105 EP S105 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900421 ER PT J AU Lacey, JV Brinton, LA Leitzmann, MF Chang, SC Mouw, T Hollenbeck, A Schatzkin, A AF Lacey, J. V., Jr. Brinton, L. A. Leitzmann, M. F. Chang, S-C Mouw, T. Hollenbeck, A. Schatzkin, A. TI Endometrial cancer and menopausal estrogen plus progestin therapy. A cohort study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S161 EP S161 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901124 ER PT J AU Laurin, D Masaki, K White, LR Launer, LJ AF Laurin, D. Masaki, K. White, L. R. Launer, L. J. TI Ankle-brachial index in dementia. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S239 EP S239 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901431 ER PT J AU Law, DCG Longnecker, MP AF Law, D. C. G. Longnecker, M. P. TI Does obesity reduce fecundity for specific subgroups? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S75 EP S75 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900300 ER PT J AU Lim, U Morton, LM Subar, AF Stolzenberg-Solomon, R Baris, D Leitzmann, M Kipnis, V Mouw, T Carroll, L Schatzkin, A Hartge, P AF Lim, U. Morton, L. M. Subar, A. F. Stolzenberg-Solomon, R. Baris, D. Leitzmann, M. Kipnis, V. Mouw, T. Carroll, L. Schatzkin, A. Hartge, P. TI Alcohol intake and risk of non-Hodgkin lymphomas in the prospective NIH-AARP Diet and Health Study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, DCEG, NIH, DHHS, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S89 EP S89 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900354 ER PT J AU Linet, M Hatch, M AF Linet, M. Hatch, M. TI High-yield cancer data from low-dose radiation exposures: Medical radiation exposures, nuclear workers, Chernobyl. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S246 EP S246 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901459 ER PT J AU Lynch, S Anderson, L Pickle, L Barr, T Winn, D AF Lynch, S. Anderson, L. Pickle, L. Barr, T. Winn, D. TI The Long Island Geographic Information System (LI GIS). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S26 EP S26 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900103 ER PT J AU MacLehose, RF Dunson, DB Herring, AH Kaufman, JS Hartmann, KE Poole, C Savitz, DA AF MacLehose, R. F. Dunson, D. B. Herring, A. H. Kaufman, J. S. Hartmann, K. E. Poole, C. Savitz, D. A. TI Bayesian methods for highly correlated data: An application to disinfection by-products and spontaneous abortion. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S227 EP S227 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901384 ER PT J AU Mahajan, R Blair, A Lynch, C Schroeder, P Hoppin, J Sandler, D Alavanja, M AF Mahajan, R. Blair, A. Lynch, C. Schroeder, P. Hoppin, J. Sandler, D. Alavanja, M. TI Fonofos exposure and incident cancer in the Agricultural Health Study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S235 EP S235 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901415 ER PT J AU Mitrou, PN Reedy, J Wirfalt, E Subar, AF Kipnis, V Midthune, D Mouw, T Hollenbeck, A Schatzkin, A Leitzmann, MF AF Mitrou, P. N. Reedy, J. Wirfalt, E. Subar, A. F. Kipnis, V. Midthune, D. Mouw, T. Hollenbeck, A. Schatzkin, A. Leitzmann, M. F. TI Adherence to a Mediterranean-type diet and mortality in the NIH-AARP diet and health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Natl Inst Hlth, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S42 EP S42 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900167 ER PT J AU Moore, SC Mayne, S Graubard, BI Schatzkin, A Albanes, D Schairer, C Leitzmann, MF AF Moore, S. C. Mayne, S. Graubard, B. I. Schatzkin, A. Albanes, D. Schairer, C. Leitzmann, M. F. TI Association of all-cause mortality with measured body-mass index from a prior decade. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S39 EP S39 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900155 ER PT J AU Nguyen, R Cooper, G AF Nguyen, R. Cooper, G. CA Carolina Lupus Study TI Anticardiolipin antibodies and spontaneous abortion as risk factors for lupus. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S147 EP S147 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901068 ER PT J AU Patel, K Harris, T Faulhaber, M Angleman, S Bauer, D Connelly, S Kuller, L Guralnik, J AF Patel, K. Harris, T. Faulhaber, M. Angleman, S. Bauer, D. Connelly, S. Kuller, L. Guralnik, J. CA Hlth ABC Study TI Racial variation in the relationship of anemia with mortality in older adults. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIH, Hlth ABC Study, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S174 EP S174 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901174 ER PT J AU Perkins, NJ Schisterman, EF Vexler, A AF Perkins, N. J. Schisterman, E. F. Vexler, A. TI ROC curve inference from a sample with a limit of detection. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, DESPR, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S74 EP S74 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900296 ER PT J AU Rajaraman, P Stewart, PA Samet, JM Schwartz, BS Linet, MS Zahm, SH Rothman, N Yeager, M Fine, HA Black, PM Loeffler, J Shapiro, WR Selker, RG Inskip, PD AF Rajaraman, P. Stewart, P. A. Samet, J. M. Schwartz, B. S. Linet, M. S. Zahm, S. H. Rothman, N. Yeager, M. Fine, H. A. Black, P. M. Loeffler, J. Shapiro, W. R. Selker, R. G. Inskip, P. D. TI Lead, genetic susceptibility and risk of adult brain tumors. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S158 EP S158 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901111 ER PT J AU Rajaraman, P Sigurdson, AJ Doody, MM Freedman, DM Hauptmann, M Ron, E Alexander, BH Linet, MS AF Rajaraman, P. Sigurdson, A. J. Doody, M. M. Freedman, D. M. Hauptmann, M. Ron, E. Alexander, B. H. Linet, M. S. TI Lung cancer incidence among US Radiologic Technologists, 1983-1998. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S108 EP S108 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900431 ER PT J AU Sakoda, L Graubard, B Gao, Y Deng, J Hsing, A AF Sakoda, L. Graubard, B. Gao, Y. Deng, J. Hsing, A. TI Biomarkers of obesity and westernization: Implications for cancer etiology. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S41 EP S41 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900163 ER PT J AU Saldana, TM Basso, O Hoppin, JA Baird, DD Knott, C Alavanja, MCR Blair, A Sandler, DP AF Saldana, T. M. Basso, O. Hoppin, J. A. Baird, D. D. Knott, C. Alavanja, M. C. R. Blair, A. Sandler, D. P. TI Pesticide use and gestational diabetes mellitus among wives of farmers in the Agricultural Health Study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S77 EP S77 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900306 ER PT J AU Samanic, C Kogevinas, M Dosemeci, M Malats, N Real, F Garcia-Closas, M Serra, C Carrato, A Garcia-Closas, R Sala, M Lloreta, J Tardon, A Rothman, N Silverman, D AF Samanic, C. Kogevinas, M. Dosemeci, M. Malats, N. Real, F. Garcia-Closas, M. Serra, C. Carrato, A. Garcia-Closas, R. Sala, M. Lloreta, J. Tardon, A. Rothman, N. Silverman, D. TI Smoking and bladder cancer in Spain: Effects of tobacco type, timing, ETS and gender. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. RI Serra, C/E-6879-2014; Lloreta, J/I-2112-2014; Kogevinas, Manolis/C-3918-2017 OI Serra, C/0000-0001-8337-8356; Lloreta, J/0000-0003-1644-9470; NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S110 EP S110 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900438 ER PT J AU Sansbury, L Albert, P Yu, B Schatzkin, A Lanza, E AF Sansbury, L. Albert, P. Yu, B. Schatzkin, A. Lanza, E. CA Polyp Prevention Trial Study Grp TI Adenoma characteristics associated with recurrent colorectal adenomas: Results from the Polyp Prevention Trial - Continued Follow-Up Study (PPT-CFS). SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S105 EP S105 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900419 ER PT J AU Scheidt, P AF Scheidt, P. TI The goals, objectives and design of the NCS: Current status. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S243 EP S243 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901450 ER PT J AU Schisterman, EF Vexler, A Liu, A AF Schisterman, E. F. Vexler, A. Liu, A. TI To pool or not to pool, from whether to when: Applications of pooling to biospecimen with incomplete measurements. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S225 EP S225 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901378 ER PT J AU Simonsen, L Viboud, C Taylor, RJ Miller, MA AF Simonsen, L. Viboud, C. Taylor, R. J. Miller, M. A. TI Mortality benefits of influenza vaccination in the elderly. An ongoing controversy. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S168 EP S168 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901152 ER PT J AU Smith, SM Goldstein, RB Grant, BF AF Smith, S. M. Goldstein, R. B. Grant, B. F. TI Racial and ethnic disparities in treatment for alcohol use, drug use, mood, and anxiety disorders. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S218 EP S218 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901351 ER PT J AU Stolzenberg-Solomon, RZ Cross, AJ Silverman, D Thompson, FE Kipnis, V Subar, AF Hollenbeck, A Schatzkin, A Sinha, R AF Stolzenberg-Solomon, R. Z. Cross, A. J. Silverman, D. Thompson, F. E. Kipnis, V. Subar, A. F. Hollenbeck, A. Schatzkin, A. Sinha, R. TI Meat and meat mutagen intake and pancreatic cancer risk in the NIH-AARP Diet and Health Study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, NIH, Rockville, MD 20852 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S109 EP S109 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900436 ER PT J AU Thiebaut, A Kipnis, V Chang, SC Subar, A Thompson, F Rosenberg, P Leitzmann, M Hollenbeck, A Schatzkin, A AF Thiebaut, A. Kipnis, V. Chang, S-C Subar, A. Thompson, F. Rosenberg, P. Leitzmann, M. Hollenbeck, A. Schatzkin, A. TI Dietary fat intake and breast cancer risk in the NIH-AARP Diet and Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S96 EP S96 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900385 ER PT J AU Valcin, M Henneberger, PK Kullman, GJ Umbach, DM London, SJ Alavanja, MCR Sandler, DP Hoppin, JA AF Valcin, M. Henneberger, P. K. Kullman, G. J. Umbach, D. M. London, S. J. Alavanja, M. C. R. Sandler, D. P. Hoppin, J. A. TI Risk factors for chronic bronchitis among nonsmoking farm women in the agricultural health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900268 ER PT J AU Wacholder, S AF Wacholder, S. TI Population stratification in genetic association studies: Bias, type I error and type II error. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S84 EP S84 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900336 ER PT J AU Whitcomb, BW Schisterman, EF Flaws, JA Klebanoff, MA Luo, X Chegini, N AF Whitcomb, B. W. Schisterman, E. F. Flaws, J. A. Klebanoff, M. A. Luo, X. Chegini, N. TI Circulating cytokines and early fetal loss. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NICHD, DESPR, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S54 EP S54 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900214 ER PT J AU Winn, D Hall, I AF Winn, D. Hall, I. TI Research in the public eye: The Long Island Breast Cancer Study and research on Gulf War illness. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S165 EP S165 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132901140 ER PT J AU Wright, M Weinstein, S Lawson, K Albanes, D Subar, A Kipnis, V Mouw, T Hurwitz, P Schatzkin, A Leitzmann, M AF Wright, M. Weinstein, S. Lawson, K. Albanes, D. Subar, A. Kipnis, V. Mouw, T. Hurwitz, P. Schatzkin, A. Leitzmann, M. TI Vitamin E and prostate cancer risk in the NIH-AARP diet and health study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S39 EP S39 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900156 ER PT J AU Zhu, HH T Gao, Y Blair, A Ji, BT Samet, JM Yang, G Shu, XO Lubin, J Chow, WH Zheng, W Cantor, KP AF Zhu, H. H. T Gao, Y. Blair, A. Ji, B. T. Samet, J. M. Yang, G. Shu, X. O. Lubin, J. Chow, W. H. Zheng, W. Cantor, K. P. TI Secondhand smoke and breast cancer risk: A community-based prospective cohort study. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA C1 NCI, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2006 VL 163 IS 11 SU S BP S98 EP S98 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 051AP UT WOS:000238132900390 ER PT J AU Longley, MJ Clark, S Man, CYW Hudson, G Durham, SE Taylor, RW Nightingale, S Turnbull, DM Copeland, WC Chinnery, PF AF Longley, Matthew J. Clark, Susanna Man, Cynthia Yu Wai Hudson, Gavin Durham, Steve E. Taylor, Robert W. Nightingale, Simon Turnbull, Douglass M. Copeland, William C. Chinnery, Patrick F. TI Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ACCESSORY SUBUNIT; ALPERS-SYNDROME; AUTOSOMAL-DOMINANT; MUTATIONS; BINDING; IDENTIFICATION; DEPLETION; DELETIONS; MUSCLE AB DNA polymerase gamma (pol gamma) is required to maintain the genetic integrity of the 16,569-bp human mitochondrial genome (mtDNA). Mutation of the nuclear gene for the catalytic subunit of pol gamma (POLG) has been linked to a wide range of mitochondrial diseases involving mutation, deletion, and depletion of mtDNA. We describe a heterozygous dominant mutation (c.1352G -> A/p.G451E) in POLG2, the gene encoding the p55 accessory subunit of pol gamma, that causes progressive external ophthalmoplegia with multiple mtDNA deletions and cytochrome c oxidase (COX)-deficient muscle fibers. Biochemical characterization of purified, recombinant G451E-substituted p55 protein in vitro revealed incomplete stimulation of the catalytic subunit due to compromised subunit interaction. Although G451E p55 retains a wild-type ability to bind DNA, it fails to enhance the DNA-binding strength of the p140-p55 complex. In vivo, the disease most likely arises through haplotype insufficiency or heterodimerization of the mutated and wild-type proteins, which promote mtDNA deletions by stalling the DNA replication fork. The progressive accumulation of mtDNA deletions causes COX deficiency in muscle fibers and results in the clinical phenotype. C1 Univ Newcastle Upon Tyne, Sch Med, Mitochondrial Res Grp, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, Res Triangle Pk, NC USA. Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Royal Shrewsbury Hosp, Shrewsbury, Salop, England. RP Chinnery, PF (reprint author), Univ Newcastle Upon Tyne, Sch Med, Mitochondrial Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. EM P.F.Chinnery@ncl.ac.uk RI Hudson, Gavin/E-7117-2017 FU Intramural NIH HHS; Wellcome Trust [074454] NR 26 TC 128 Z9 131 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2006 VL 78 IS 6 BP 1026 EP 1034 DI 10.1086/504303 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 042TZ UT WOS:000237553800011 PM 16685652 ER PT J AU Clarimon, J Scholz, S Fung, HC Hardy, J Eerola, J Hellstrom, O Chen, CM Wu, YR Tienari, PJ Singleton, A AF Clarimon, J Scholz, S Fung, HC Hardy, J Eerola, J Hellstrom, O Chen, CM Wu, YR Tienari, PJ Singleton, A TI Conflicting results regarding the semaphorin gene (SEMA5A) and the risk for Parkinson disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. Univ Helsinki, Biomedicum, Neurosci Programme, FIN-00014 Helsinki, Finland. Seinajoki Cent Hosp, Dept Neurol, Seinajoki, Finland. RP Clarimon, J (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A1000,MSC 3707,35 Lincoln Dr, Bethesda, MD 20892 USA. EM jclarimon@santpau.es RI Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012; Hardy, John/C-2451-2009; OI Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 5 TC 45 Z9 47 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUN PY 2006 VL 78 IS 6 BP 1082 EP 1084 DI 10.1086/504727 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 042TZ UT WOS:000237553800019 PM 16685660 ER PT J AU Baccarelli, A Khmelnitskii, O Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Rice, C Dosemeci, M AF Baccarelli, A Khmelnitskii, O Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Rice, C Dosemeci, M TI Risk of lung cancer from exposure to dusts and fibers in Leningrad Province, Russia SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE glass wool; linen dust; man-made vitreous fibers; occupation; paper dust; particles; quartz ID COHORT MORTALITY; PAPER WORKERS; PULP AB Background Exposures to several dusts and fibers (DFs) have been established or suggested as etiologic factors for lung cancer. Methods To investigate lung cancer risk in relation to exposure to DFs, we identified 540 pathologically-diagnosed lung cancer cases and 582 controls from the 1993-1998 autopsy records of the 88 hospitals of Leningrad Province, Russia. Lifetime job-specific exposure measurements were available for 15 organic, 15 man-made and 28 natural-inorganic agents. Results In male workers, increased risks were found for linen dust (OR=3.68, 95% CI 1.00-13.6, adjusted for age, smoking and residence), and unspecified DFs (OR = 1.44, 95% CI1.07-1.94). Small non-significant excess risks were observed for quartz dust (OR = 1.27; 95% CI 0.83-1.93) and man-made vitreous fibers (MMVFs) (OR = 1.82, 95% CI 0.883.75). In female subjects, risks were non-significantly associated with paperdust (OR = 1.77, 95% CI0.74-4.20), and unspecified DFs (OR = 1.52, 95% CI 0.77-3.03). Conclusions The study showed increased lung cancer risk for selected categories of DFs. C1 Univ Milan, Dept Environm & Occupat Hlth, EPOCA Res Ctr Occupat Clin & Environm Epidemiol, Clin L Devoto, I-20122 Milan, Italy. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Milan, Dept Occupat Hlth, Clin Lavoro L Devoto, I-20122 Milan, Italy. Med Acad Postgrad Educ, St Petersburg, Russia. Reg Ctr Hyg & Sanitat, St Petersburg, Russia. Leningrad Oblast Pathol Bur, St Petersburg, Russia. Univ Cincinnati, Coll Med, Dept Environm Hlth, Cincinnati, OH 45267 USA. RP Baccarelli, A (reprint author), Univ Milan, Dept Environm & Occupat Hlth, EPOCA Res Ctr Occupat Clin & Environm Epidemiol, Clin L Devoto, Via San Barnava 8, I-20122 Milan, Italy. EM andrea.baccarelli@unimi.it OI Baccarelli, Andrea/0000-0002-3436-0640 NR 21 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 2006 VL 49 IS 6 BP 460 EP 467 DI 10.1002/ajim.20316 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 046CB UT WOS:000237787900007 PM 16586409 ER PT J AU Lash, JP Wang, XL Greene, T Gadegbeku, CA Hall, Y Jones, K Kusek, JW Sika, M Unruh, M AF Lash, JP Wang, XL Greene, T Gadegbeku, CA Hall, Y Jones, K Kusek, JW Sika, M Unruh, M CA African Amer Study Kidney Dis Hype TI Quality of life in the African American Study of Kidney Disease and Hypertension: Effects of blood pressure management SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE health-related quality of life (HRQOL); hypertension; African Americans; chronic kidney disease (CKD) ID CHRONIC RENAL-INSUFFICIENCY; CONTROLLED TRIAL; HEALTH; SF-36 AB Background. The African American Study of Kidney Disease and Hypertension was a multicenter trial comparing the effects of 2 levels of blood pressure control (usual or low goal) and initial therapy with metoprolol, ramipril, or amlodipine. We examined effects of treatment-group assignment on health-related quality of life (HRQOL) measures and reported symptoms during 4 years of follow-up. Methods: HRQOL was assessed at baseline and annually by using the Medical Outcomes Study 36-Item Short Form (SF-36) and a symptom checklist. Using a 2-slope model, treatment effects were evaluated for change from baseline to year 1 and for average change during the first 4 years of follow-up. Results: A total of 1,094 participants were randomly assigned. Average age was 55 years, 61% were men, and the mean of the first glomerular filtration rate in the study was 46 mL/min/1.73 m(2) (0.76 mL/s). No significant differences in HRQOL were seen between the low- and usual-blood-pressure groups. Reported side effects also were similar between blood-pressure groups. Mean Physical Health Component (PHC) and Mental Health Component (MHC) scores had a significantly smaller decrease in the ramipril than metoprolol group in both the initial period from baseline to year 1 (PHC, 2.08 +/- 0.56; MHC, 1.89 +/- 0.62) and during the first 4 years of follow-up (PHC, 1.60 +/- 0.44; MHC, 1.48 +/- 0.48). The MHC also had a slightly smaller decrease during the first 4 years in the ramipril group than amlodipine group (1.20 +/- 0.61). Conclusion Aggressive blood pressure control is well tolerated in African Americans with hypertensive kidney disease, measured by using the SF-36 and reported symptoms. The clinical significance of smaller decreases in PHC and MHC scores in the ramipril compared with metoprolol group is not clear. C1 Univ Illinois, Dept Med, Sect Nephrol MC 793, Chicago, IL 60612 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Texas SW, Dallas, TX USA. NIDDK, NIH, Bethesda, MD USA. Vanderbilt Univ, Nashville, TN USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Lash, JP (reprint author), Univ Illinois, Dept Med, Sect Nephrol MC 793, 820 S Wood St, Chicago, IL 60612 USA. EM jplash@uic.edu FU NCRR NIH HHS [2P20 RR11104, 5M01 RR-00071, M01 RR-00080, M01 RR00827, P20-RR11145]; PHS HHS [M01 00032] NR 27 TC 11 Z9 13 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 2006 VL 47 IS 6 BP 956 EP 964 DI 10.1053/j.ajkd.2006.02.175 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 054PF UT WOS:000238390400003 PM 16731290 ER PT J AU Shen, DF Yuen, HKL Galita, DA Chan, NR Chan, C AF Shen, DF Yuen, HKL Galita, DA Chan, NR Chan, C TI Detection of Chlamydia pneumoniae in a bilateral orbital mucosa-associated lymphoid tissue lymphoma SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HELICOBACTER-PYLORI; PSITTACI AB PURPOSE: To detect Chlamydia pneumoniae (C. pneumoniae) gene in a patient with bilateral orbital musoca-associated lymphoid tissue (MALT) lymphoma. DESIGN: Interventional case report. METHODS: A 47-year-old Chinese man with recurrent bilateral orbital masses underwent surgical biopsy. Ophthalmologic and radiographic examinations, routine histology, immunohistochernistry, and molecular analysis for immunoglobulin heavy chain (IgH), bcl-2/IgH gene translocation, and Chlamydia genes were performed. RESULTS: Pathology revealed orbital MALT lymphoma with B-cell monoclonality. In addition to IgH gene rearrangement, C. pneumoniae DNA was detected in the lymphoma. CONCLSIONS: The finding of C. pneumoniae molecular signatures in this case suggests a possible association of Chlamydia and orbital MALT lymphoma. The infection may contribute to the development of the lymphoma. C1 Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. RP Chan, C (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22] NR 7 TC 10 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2006 VL 141 IS 6 BP 1162 EP 1163 DI 10.1016/j.ajo.2006.01.067 PG 2 WC Ophthalmology SC Ophthalmology GA 056AI UT WOS:000238492600038 PM 16765702 ER PT J AU Saika, S Ikeda, K Yamanaka, O Flanders, KC Okada, Y Miyamoto, T Kitano, A Ooshima, A Nakajima, Y Ohnishi, Y Kao, WWY AF Saika, S Ikeda, K Yamanaka, O Flanders, KC Okada, Y Miyamoto, T Kitano, A Ooshima, A Nakajima, Y Ohnishi, Y Kao, WWY TI Loss of tumor necrosis factor alpha potentiates transforming growth factor beta-mediated pathogenic tissue response during wound healing SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN DERMAL FIBROBLASTS; RECEPTOR KNOCKOUT MICE; GENE-EXPRESSION; ALKALI BURNS; TNF-ALPHA; CORNEAL EPITHELIUM; APOLIPOPROTEIN-E; SMAD PROTEINS; RAT CORNEA; CELLS AB Animal cornea is an avascular transparent tissue that is suitable for research on wound heating-related scarring and neovascularization. Here we show that loss of tumor necrosis factor alpha (TNF alpha) potentiates the undesirable, pathogenic response of wound healing in an alkali-burned cornea in mice. Excessive invasion of macrophages; and subsequent formation of a vascularized scar tissue were much more marked in TNF alpha-null knockout (KO) mice than in wild-type mice. Such an unfavorable outcome in KO mice was abolished by Smad7 gene introduction, indicating the involvement of transforming growth factor beta or activin/Smad signaling. Bone marrow transplantation from wild-type mice normalized healing of the KO mice, suggesting the involvement of bone marrow-derived inflammatory cells in this phenomenon. Coculture experiments showed that loss of TNF alpha in macrophages, but not in fibroblasts, augmented the fibroblast activation as determined by detection of alpha-smooth muscle actin, the hallmark of myofibroblast generation, mRNA expression of collagen I alpha 2 and connective tissue growth factor, and detection of collagen protein. TNF alpha in macrophages may be required to suppress undesirable excessive inflammation and scarring, both of which are promoted by transforming growth factor beta, and for restoration of tissue architecture in a healing alkali-burned cornea in mice. C1 Wakayama Med Coll, Dept Ophthalmol, Wakayama 6410012, Japan. Wakayama Med Coll, Dept Pathol, Wakayama 6410012, Japan. Osaka City Univ, Grad Sch Med, Dept Anat, Osaka 558, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH USA. RP Saika, S (reprint author), Wakayama Med Coll, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp FU NEI NIH HHS [EY-13755, R01 EY013755] NR 52 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUN PY 2006 VL 168 IS 6 BP 1848 EP 1860 DI 10.2353/ajpath.2006.050980 PG 13 WC Pathology SC Pathology GA 048YY UT WOS:000237983700007 PM 16723700 ER PT J AU Makino, A Prossnitz, ER Bunemann, M Wang, JM Yao, WJ Schmid-Schoenbein, GW AF Makino, A Prossnitz, ER Bunemann, M Wang, JM Yao, WJ Schmid-Schoenbein, GW TI G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE leukocyte; constitutive activity; mechanotransduction; formyl peptide receptor ID VASCULAR ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; FORMYL-PEPTIDE; CONSTITUTIVE ACTIVITY; HL-60 CELLS; REGULATORY PROTEINS; SIGNAL-TRANSDUCTION; ACTIVATION; EXPRESSION; MIGRATION AB Many cells respond to fluid shear stress but in a cell type-specific fashion. Fluid shear stress applied to leukocytes serves to control pseudopod formation, migration, and other functions. Specifically, fresh neutrophils or neutrophilic leukocytes derived from differentiated HL60 cells respond to fluid shear stress by cytoplasmic pseudopod retraction. The membrane elements that sense fluid shear and induce such a specific response are still unknown, however. We hypothesized that membrane receptors may serve as fluid shear sensors. We found that fluid shear decreased the constitutive activity of G protein-coupled receptors (GPCRs). Inhibition of GPCR constitutive activity by inverse agonists abolished fluid shear stress-induced cell area reduction. Among the GPCRs in neutrophils, the formyl peptide receptor (FPR) exhibits relatively high constitutive activity. Undifferentiated HL60 cells that lacked FPR formed few pseudopods and showed no detectable response to fluid shear stress, whereas expression of FPR in undifferentiated HL60 cells caused pseudopod projection and robust pseudopod retraction during fluid shear. FPR small interfering RNA-transfected differentiated HL60 cells exhibited no response to fluid shear stress. These results suggest that GPCRs serve as mechanosensors for fluid shear stress in neutrophils by decreasing its constitutive activity and reducing pseudopod projection. C1 Univ Calif San Diego, Dept Bioengn, Whitaker Inst Biomed Engn, La Jolla, CA 92093 USA. Univ New Mexico, Hlth Sci Ctr, Dept Cell Biol & Physiol, Albuquerque, NM 87131 USA. Univ Wurzburg, Dept Pharmacol & Toxicol, Wurzburg, Germany. NCI, Labs Mol Immunoregulat, Ctr Canc Res, Frederick, MD 21701 USA. RP Schmid-Schoenbein, GW (reprint author), Univ Calif San Diego, Dept Bioengn, Whitaker Inst Biomed Engn, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM gwss@bioeng.ucsd.edu RI Prossnitz, Eric/B-4543-2008; OI Prossnitz, Eric/0000-0001-9190-8302 FU NHLBI NIH HHS [HL-10881, HL-43026] NR 42 TC 53 Z9 55 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JUN PY 2006 VL 290 IS 6 BP C1633 EP C1639 DI 10.1152/ajpcell.00576.2005 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 040VA UT WOS:000237407600020 PM 16436471 ER PT J AU Kim, H Pennisi, PA Gavrilova, O Pack, S Jou, W Setser-Portas, J East-Palmer, J Tang, Y Manganiello, VC LeRoith, D AF Kim, H Pennisi, PA Gavrilova, O Pack, S Jou, W Setser-Portas, J East-Palmer, J Tang, Y Manganiello, VC LeRoith, D TI Effect of adipocyte beta(3)-adrenergic receptor activation on the type 2 diabetic MKR mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin-like growth factor I receptor mutation; type 2 diabetes ID BETA-ADRENOCEPTOR AGONIST; BROWN ADIPOSE-TISSUE; ZUCKER FA/FA RATS; INSULIN SENSITIVITY; SKELETAL-MUSCLE; BETA-3-ADRENERGIC AGONIST; ADRENERGIC-RECEPTORS; GLUCOSE-UTILIZATION; TRANSGENIC MODEL; LIPID-METABOLISM AB The antiobesity and antidiabetic effects of the beta(3)-adrenergic agonists were investigated on nonobese type 2 diabetic MKR mice after injection with a beta(3)-adrenergic agonist, CL-316243. An intact response to acute CL-316243 treatment was observed in MKR mice. Chronic intraperitoneal CL-316243 treatment of MKR mice reduced blood glucose and serum insulin levels. Hyperinsulinemic euglycemic clamps exhibited improvement of the whole body insulin sensitivity and glucose homeostasis concurrently with enhanced insulin action in liver and adipose tissue. Treating MKR mice with CL-316243 significantly lowered serum and hepatic lipid levels, in part due to increased whole body triglyceride clearance and fatty acid oxidation in adipocytes. A significant reduction in total body fat content and epididymal fat weight was observed along with enhanced metabolic rate in both wild-type and MKR mice after treatment. These data demonstrate that beta(3)-adrenergic activation improves the diabetic state of nonobese diabetic MKR mice by potentiation of free fatty acid oxidation by adipose tissue, suggesting a potential therapeutic role for beta(3)-adrenergic agonists in nonobese diabetic subjects. C1 USDA ARS, Beltsville Agr Res Ctr, Diabet Branch, Beltsville, MD 20705 USA. USDA ARS, Mouse Metab Core Lab, NIDDK, Beltsville, MD 20705 USA. USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), CUNY Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, 1 Gustave Levy Pl 1055, New York, NY 10029 USA. EM derek.leroith@mssu.edu FU Intramural NIH HHS NR 44 TC 28 Z9 32 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2006 VL 290 IS 6 BP E1227 EP E1236 DI 10.1152/ajpendo.00344.2005 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 046HX UT WOS:000237803300022 PM 16682489 ER PT J AU Ola, MS Berkich, DA Xu, YP King, MT Gardner, TW Simpson, I LaNoue, KF AF Ola, MS Berkich, DA Xu, YP King, MT Gardner, TW Simpson, I LaNoue, KF TI Analysis of glucose metabolism in diabetic rat retinas SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetic retinopathy; hyperglycemia; reactive oxygen species; mitochondria; glycolysis; polyols ID PROTEIN-KINASE-C; FOCUSED MICROWAVE IRRADIATION; INDUCED OXIDATIVE STRESS; POLYOL PATHWAY; MITOCHONDRIAL SUPEROXIDE; EXPERIMENTAL GALACTOSEMIA; HYPERGLYCEMIC DAMAGE; ALDOSE REDUCTASE; FREE-RADICALS; NITRIC-OXIDE AB This study was conceived in an effort to understand cause and effect relationships between hyperglycemia and diabetic retinopathy. Numerous studies show that hyperglycemia leads to oxidative stress in the diabetic retinas, but the mechanisms that generate oxidative stress have not been resolved. Increased electron pressure on the mitochondrial electron transfer chain, increased generation of cytosolic NADH, and decreases in cellular NADPH have all been cited as possible sources of reactive oxygen species and nitrous oxide. In the present study, excised retinas from control and diabetic rats were exposed to euglycemic and hyperglycemic conditions. Using a microwave irradiation quenching technique to study retinas of diabetic rats in vivo, glucose, glucose-derived metabolites, and NADH oxidation/reduction status were measured. Studying excised retinas in vitro, glycolytic flux, lactate production, and tricarboxylic acid cycle flux were evaluated. Enzymatically assayed glucose 6-phosphate and fructose 6-phosphate were only slightly elevated by hyperglycemia and/or diabetes, but polyols were increased dramatically. Cytosolic NADH-to-NAD ratios were not elevated by hyperglycemia nor by diabetes in vivo or in vitro. Tricarboxylic acid cycle flux was not increased by the diabetic state nor by hyperglycemia. On the other hand, small increases in glycolytic flux were observed with hyperglycemia, but glycolytic flux was always lower in diabetic compared with control animals. An observed decrease in activity of glyceraldehyde-3-phosphate dehydrogenase may be partially responsible for slow glycolytic flux for retinas of diabetic rats. Therefore, it is concluded that glucose metabolism, downstream of hexokinase, is not elevated by hyperglycemia or diabetes. Metabolites upstream of glucose such as the sorbitol pathway (which decreases NADPH) and polyol synthesis are increased. C1 Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Ophthalmol, Hershey, PA 17033 USA. NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. RP LaNoue, KF (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, POB 850, Hershey, PA 17033 USA. EM klanoue@psu.edu OI Gardner, Thomas/0000-0002-5112-5810 NR 56 TC 47 Z9 48 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUN PY 2006 VL 290 IS 6 BP E1057 EP E1067 DI 10.1152/ajpendo.00323.2005 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 046HX UT WOS:000237803300001 PM 16380392 ER PT J AU Heilig, EA Thompson, KJ Molina, RM Ivanov, AR Brain, JD Wessling-Resnick, M AF Heilig, EA Thompson, KJ Molina, RM Ivanov, AR Brain, JD Wessling-Resnick, M TI Manganese and iron transport across pulmonary epithelium SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE transferrin; bronchoalveolar lavage fluid; macrophages ID STORE-OPERATED CHANNELS; CAPACITATIVE CA2+ ENTRY; BLOOD-BRAIN-BARRIER; 2-AMINOETHOXYDIPHENYL BORATE; PARTICULATE MATTER; CALCIUM-CHANNELS; HEK-293 CELLS; TRANSFERRIN; LUNG; EXPRESSION AB Pathways mediating pulmonary metal uptake remain unknown. Because absorption of iron and manganese could involve similar mechanisms, transferrin (Tf) and transferrin receptor (TfR) expression in rat lungs was examined. Tf mRNA was detected in bronchial epithelium, type II alveolar cells, macrophages, and bronchus-associated lymphoid tissue (BALT). Tf protein levels in lung and bronchoalveolar lavage fluid did not change in iron deficiency despite increased plasma levels, suggesting that lung Tf concentrations are regulated by local synthesis in a manner independent of body iron status. Iron oxide exposure upregulated Tf mRNA in bronchial and alveolar epithelium, macrophages, and BALT, but protein was not significantly increased. In contrast, TfR mRNA and protein were both upregulated by iron deficiency. To examine potential interactions with lung Tf, rats were intratracheally instilled with Mn-54 or Fe-59. Unlike Fe-59, interactions between Mn-54 and Tf in lung fluid were not detected. Absorption of intratracheally instilled Mn-54 from the lungs to the blood was unimpaired in Belgrade rats homozygous for the functionally defective G185R allele of divalent metal transporter-1, indicating that this transporter is also not involved in pulmonary manganese absorption. Pharmacological studies of Mn-54 uptake by A549 cells suggest that metal uptake by type II alveolar epithelial cells is associated with activities of both L-type Ca2+ channels and TRPM7, a member of the transient receptor potential melastatin subfamily. These results demonstrate that iron and manganese are absorbed by the pulmonary epithelium through different pathways and reveal the potential role for nonselective calcium channels in lung metal clearance. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Environm Hlth Proteom Facil, Boston, MA 02115 USA. RP Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM wessling@hsph.harvard.edu FU NIDDK NIH HHS [DK 60528]; NIEHS NIH HHS [ES 00002, P01 ES 012874] NR 63 TC 37 Z9 37 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2006 VL 290 IS 6 BP L1247 EP L1259 DI 10.1152/ajplung.00450.2005 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 040VG UT WOS:000237408200024 PM 16428268 ER PT J AU Morris, RG Hoorn, EJ Knepper, MA AF Morris, RG Hoorn, EJ Knepper, MA TI Hypokalemia in a mouse model of Gitelman's syndrome SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE thiazide; polyuria; polydipsia; aldosterone ID RENAL CONCENTRATING ABILITY; NA-CL COTRANSPORTER; POTASSIUM-DEPLETION; UREA TRANSPORTERS; COLLECTING DUCT; K+ SECRETION; RAT; ALDOSTERONE; MECHANISM; TUBULES AB Hypokalemia is a prominent feature of Gitelman syndrome and a common side effect of thiazide use in the treatment of hypertension. It is widely recognized that genetic or pharmacological inhibition of the renal thiazide-sensitive sodium-chloride cotransporter (NCC) initiates the potentially severe renal potassium loss observed in these settings. Surprisingly, hypokalemia has not been detected in NCC (-/-) mice maintained on normal rodent diets (Schultheis PJ, Lorenz JN, Meneton P, Nieman ML, Riddle TM, Flagella M, Duffy JJ, Doetschman T, Miller ML, and Shull GE. J Biol Chem 273: 29150-29155, 1998). We show that modest reduction of dietary potassium induced a marked reduction in plasma potassium and elevated renal potassium excretion in NCC (-/-) mice that was associated with a pronounced polydipsia and polyuria of central origin. These findings are consistent with the development of potassium depletion in NCC (-/-) mice and were not seen in wild-type mice maintained on the same low-potassium diet. In addition, plasma aldosterone levels were significantly elevated in NCC (-/-) mice even in the presence of a low-potassium diet. Collectively, these findings suggest an early central component to the polyuria of Gitelman syndrome and show that both elevated aldosterone and dietary potassium content contribute to the development of hypokalemia in Gitelman syndrome. Therefore, NCC (-/-) mice are more sensitive to reductions in dietary potassium than wild-type mice and become hypokalemic, thus more faithfully representing the Gitelman phenotype seen in humans. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Morris, RG (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM morrisr@nhlbi.nih.gov FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 24 TC 35 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2006 VL 290 IS 6 BP F1416 EP F1420 DI 10.1152/ajprenal.00421.2005 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 040HC UT WOS:000237368600018 PM 16434571 ER PT J AU Monk, CS Nelson, EE McClure, EB Mogg, K Bradley, BP Leibenluft, E Blair, RJR Chen, G Charney, DS Ernst, M Pine, DS AF Monk, CS Nelson, EE McClure, EB Mogg, K Bradley, BP Leibenluft, E Blair, RJR Chen, G Charney, DS Ernst, M Pine, DS TI Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiaty, Amer Coll Neuropsychopharmacol ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; SYMPTOM PROVOCATION; FACIAL EXPRESSIONS; SOCIAL PHOBIA; AMYGDALA RESPONSE; FEARFUL FACES; CHILDREN; BRAIN AB Objective: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder. Method: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces. Results: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished. Conclusions: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response. C1 Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. NIMH, Bethesda, MD 20892 USA. Univ Southampton, Southampton SO9 5NH, Hants, England. Mt Sinai Sch Med, New York, NY USA. RP Monk, CS (reprint author), Univ Michigan, Dept Psychol, 2000 East Hall,530 Church St, Ann Arbor, MI 48109 USA. EM csmonk@umich.edu RI Bradley, Brendan/B-9724-2008; Mogg, Karin/C-1181-2008; Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014; OI Mogg, Karin/0000-0002-2738-7378; Nelson, Eric/0000-0002-3376-2453; Bradley, Brendan/0000-0003-2801-4271 FU NIMH NIH HHS [K22 MH-068017] NR 41 TC 227 Z9 236 U1 10 U2 36 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2006 VL 163 IS 6 BP 1091 EP 1097 DI 10.1176/appi.ajp.163.6.1091 PG 7 WC Psychiatry SC Psychiatry GA 048UP UT WOS:000237972300023 PM 16741211 ER PT J AU Sublette, ME Hibbeln, JR Galfalvy, H Oquendo, MA Mann, JJ AF Sublette, ME Hibbeln, JR Galfalvy, H Oquendo, MA Mann, JJ TI Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BLOOD-CELL MEMBRANES; MAJOR DEPRESSION; CHOLESTEROL; VIOLENCE AB Objective: Low levels of docosahexaenoic acid, a polyunsaturated fatty acid, and elevated ratios of omega-6/omega-3 fatty acids are associated with major depression and, possibly, suicidal behavior. Predicting risk of future suicidal behaviors by essential fatty acid status merits examination. Method: Plasma polyunsaturated fatty acid levels in phospholipids were measured in 33 medication-free depressed subjects monitored for suicide attempt over a 2-year period. Survival analysis examined the association of plasma polyunsaturated fatty acid status and pathological outcome. Results: Seven subjects attempted suicide on follow-up. A lower docosahexaenoic acid percentage of total plasma polyunsaturated fatty acids and a higher omega-6/omega-3 ratio predicted suicide attempt. Conclusions: A low docosahexaenoic acid percentage and low omega-3 proportions of lipid profile predicted risk of suicidal behavior among depressed patients over the 2-year period. If confirmed, this finding would have implications for the neurobiology of suicide and reduction of suicide risk. C1 Columbia Univ, Dept Neurosci, NY State Psychiat Inst, New York, NY 10032 USA. NIAAA, Bethesda, MD USA. RP Mann, JJ (reprint author), Columbia Univ, Dept Neurosci, NY State Psychiat Inst, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA. EM jjm@columbia.edu RI Sublette, M/A-8391-2009 OI Sublette, M/0000-0001-7378-4262 FU NIMH NIH HHS [MH-062185, T-32 MH-6434-24] NR 15 TC 100 Z9 105 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUN PY 2006 VL 163 IS 6 BP 1100 EP 1102 DI 10.1176/appi.ajp.163.6.1100 PG 3 WC Psychiatry SC Psychiatry GA 048UP UT WOS:000237972300025 PM 16741213 ER PT J AU Fee, E AF Fee, E TI The AIDS memorial quilt SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM feee@mail.nih.gov NR 1 TC 1 Z9 1 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2006 VL 96 IS 6 BP 979 EP 979 DI 10.2105/AJPH.2006.088575 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 047UY UT WOS:000237905400014 PM 16670209 ER PT J AU Feldman, JG Minkoff, H Schneider, MF Gange, SJ Cohen, M Watts, H Gandhi, M Mocharnuk, RS Anastos, K AF Feldman, JG Minkoff, H Schneider, MF Gange, SJ Cohen, M Watts, H Gandhi, M Mocharnuk, RS Anastos, K TI Association of cigarette smoking with HIV prognosis among women in the HAART era: A report from the Women's Interagency HIV study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HOMOSEXUAL MEN; INFECTION; AIDS; PROGRESSION; PREVALENCE; COHORT AB Objective. We assessed the association of cigarette smoking with the effectiveness of highly active antiretroviral therapy (HAART) among low-income women. Methods. Data were analyzed from the Women's Interagency HIV Study, a multisite longitudinal study up to 7.9 years for 924 women representing 72% of all women who initiated HAART between July 1, 1995, and September 30, 2003. Results. When Cox's regression was used after control for age, race, hepatitis C infection, illicit drug use, previous antiretroviral therapy, and previous AIDS, smokers on HAART had poorer viral responses (hazard ratio [HR] =0.79; 95% confidence interval [Cl] =0.67, 0.93) and poorer immunologic response (HR =0.85; 95% Cl=0.73, 0.99). A greater risk of virologic rebound (HR= 1.39; 95% Cl=1.06,1.69) and more frequent immunologic failure (HR= 1.52; 95% CI = 1.18,1.96) were also observed among smokers. There was a higher risk of death (HR= 1.53; 95% Cl= 1.08, 2.19) and a higher risk of developing AIDS (HR = 1.36; 95% Cl = 1.07, 1.72) but no significant difference between smokers and nonsmokers in the risk of death due to AIDS. Conclusions. Some of the benefits provided by HAART are negated in cigarette smokers. C1 SUNY Hlth Sci Ctr Brooklyn, Dept Prevent Med & Community Hlth, New York, NY USA. SUNY Hlth Sci Ctr Brooklyn, Dept Obstet & Gynecol, Maimonides Med Ctr, New York, NY USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Cook Cty Hosp, Chicago, IL 60612 USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA. RP Feldman, JG (reprint author), Suny Downstate Med Ctr, 450 Clarkson Ave,Box 43, Brooklyn, NY 11203 USA. EM joseph.feldman@downstate.edu OI Gange, Stephen/0000-0001-7842-512X FU NIAID NIH HHS [U01-AI-34994, AI-34989, N01-AI-35161, R01 AI048483, R01 AI48483, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, U01-AI-31834, U01-AI-34993, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01 HD032632, U01-HD-32632] NR 21 TC 111 Z9 112 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2006 VL 96 IS 6 BP 1060 EP 1065 DI 10.2105/AJPH.2005.062745 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 047UY UT WOS:000237905400029 PM 16670229 ER PT J AU Walker, JKL Ahumada, A Frank, B Gaspard, R Berman, K Quackenbush, J Schwartz, DA AF Walker, JKL Ahumada, A Frank, B Gaspard, R Berman, K Quackenbush, J Schwartz, DA TI Multistrain genetic comparisons reveal CCR5 as a receptor involved in airway hyperresponsiveness SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE airway hyperresponsiveness; asthma; CCR5; microarray; multistrain ID MICROARRAY ANALYSIS; CLUSTER-ANALYSIS; MESSENGER-RNA; PROTEIN; INFLAMMATION; CHEMOKINES; ASTHMA; ACTIVATION; DISEASE; LIGASES AB Asthma is a ubiquitous disease with a broad range of clinical phenotypes. To better understand the complex genetic and environmental interactions underlying asthma, we compared the gene-gene interactions of four genetically distinct mouse strains that demonstrate biologically distinct responses to allergen. Using DNA microarrays and knock-out mouse studies, we showed that CCR5 plays a definitive role in the development of ovalbumin-induced allergic airway inflammatory disease. In addition, gene expression profiling data have revealed other potential novel targets for therapeutics-based research and has enhanced the understanding of the molecular mechanisms underlying the etiology of "asthma." C1 Duke Univ, Med Ctr, Dept Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. Inst Genom Res, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Walker, JKL (reprint author), Duke Univ, Med Ctr, Dept Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. EM walke082@mc.duke.edu FU NHLBI NIH HHS [U01 HL66580-01] NR 39 TC 8 Z9 9 U1 1 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUN PY 2006 VL 34 IS 6 BP 711 EP 718 DI 10.1165/rcmb.2005-0314OC PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 048QT UT WOS:000237962300012 PM 16474097 ER PT J AU Natori, S Lai, SH Finn, JP Gomes, AS Hundley, WG Jerosch-Herold, M Pearson, G Sinha, S Arai, A Lima, JAC Bluemke, DA AF Natori, S Lai, SH Finn, JP Gomes, AS Hundley, WG Jerosch-Herold, M Pearson, G Sinha, S Arai, A Lima, JAC Bluemke, DA TI Cardiovascular function in multi-ethnic study of atherosclerosis: Normal values by age, sex, and ethnicity SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE atherosclerosis; cardiac function; cardia imaging; ejection fraction; heart; left ventricle; left ventricle mass; MRI ID LEFT-VENTRICULAR MASS; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; CINE MAGNETIC-RESONANCE; TERM ENALAPRIL THERAPY; INTERSTUDY REPRODUCIBILITY; GENDER-DIFFERENCES; M-MODE; HYPERTENSION; POPULATION; VOLUMES AB OBJECTIVE. MRI provides accurate and high-resolution measurements of cardiac anatomy and function. The purpose of this study was to describe the imaging protocol and normal values of left ventricular (LV) function and mass in the Multi-Ethnic Study of Atherosclerosis (MESA). SUBJECTS AND METHODS. Eight hundred participants (400 men, 400 women) in four age strata (45-54, 55-64, 65-74, 75-84 years) were chosen at random. Participants with the following known cardiovascular risk factors were excluded: current smoker, systolic blood pressure >140 turn Hg, diastolic blood pressure >90 min Hg, fasting glucose >110 mg/dL, total cholesterol >240 mg/dL, and high-density lipoprotein (HDL) cholesterol <40 mg/dL. Cardiac MR images were analyzed using MASS software (version 4.2). Mean values, SDs, and correlation coefficients in relationship to patient age were calculated. RESULTS. There were significant differences in LV volumes and mass between men and women. LV volumes were inversely associated with age (p < 0.05) for both sexes except for the LV end-systolic volume index. For men, LV mass was inversely associated with age (slope = -0.72 g/year, p = 0.0021), but LV mass index was not associated with age (slope = -0.179 g/m(2)/year, p = 0.075). For women, LV mass (slope = -0.15 g/year, p = 0.30) and LV mass index (slope = 0.0044 g/m(2)/year, p = 0.95) were not associated with age. LV mass was the largest in the African-American group (men, 181.6 +/- 35.8 [SD] g; women, 128.8 +/- 28.1 g) and was smallest in the Asian-American group (men, 129.1 +/- 20.0 g; women, 89.4 +/- 13.3 g). CONCLUSION. The normal LV differs in volume and mass between sexes and among certain ethnic groups. When indexed by body surface area, LV mass was independent of age for both sexes. Studies that assess cardiovascular risk factors in relationship to cardiac function and structure need to account for these normal variations in the population. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Radiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Epidemiol, Baltimore, MD USA. Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27109 USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. RP Bluemke, DA (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, Dept Radiol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM dbluemke@jhmi.edu RI Jerosch-Herold, Michael/F-2496-2010; OI Bluemke, David/0000-0002-8323-8086 FU NHLBI NIH HHS [N01-HC-95160, N01-HC-95159, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95168] NR 32 TC 218 Z9 220 U1 1 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2006 VL 186 IS 6 SU S BP S357 EP S365 DI 10.2214/AJR.04.1868 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 047AE UT WOS:000237851400004 PM 16714609 ER PT J AU Catov, JM Newman, AB Kelsey, SF Roberts, JM Sutton-Tyrrell, KC Garcia, M Ayonayon, HN Tylavsky, F Ness, RB AF Catov, JM Newman, AB Kelsey, SF Roberts, JM Sutton-Tyrrell, KC Garcia, M Ayonayon, HN Tylavsky, F Ness, RB TI Accuracy and reliability of maternal recall of infant birth weight among older women SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE recall; reproductive history; reproducibility of results ID PREGNANCY-RELATED EVENTS; VALIDATION; VALIDITY; RECORDS; MOTHERS; COHORT; HEALTH AB PURPOSE: We assessed the accuracy and reliability of maternal recall of infant birth weight 35 to 70 years after delivery. METHODS: A total of 120 well functioning women (mean age 80 years; 45% Black) reported the birth weight for each live birth and then provided documentation of birth weights (n = 22) or reported birth weights a second time (n = 98). RESULTS: Agreement between recalled and documented birth weights was high for first births (ICC 0.96) but moderate for subsequent births (ICC = 0.59). Maternal recall was highly reliable for first births (r = 0.95) and subsequent births (r = 0.87), and reliability remained high when considered separately by race, education, income, and age. CONCLUSION: Women report accurate and reliable infant birth-weight data an average of 5 7 years after delivery, and recall is particularly precise for first births. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Magee Womens Res Inst, Pittsburgh, PA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN USA. RP Catov, JM (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM jmcst43@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 17 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD JUN PY 2006 VL 16 IS 6 BP 429 EP 431 DI 10.1016/j.annepidem.2005.09.004 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 049ZS UT WOS:000238057500003 PM 16280248 ER PT J AU Gubbins, PO Krishna, G Sansone-Parsons, A Penzak, SR Dong, L Martinho, M Anaissie, EJ AF Gubbins, PO Krishna, G Sansone-Parsons, A Penzak, SR Dong, L Martinho, M Anaissie, EJ TI Pharmacokinetics and safety of oral posaconazole in neutropenic stem cell transplant recipients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITIES; TRIAZOLE ANTIFUNGAL; ASPERGILLUS SPP.; HEALTHY-SUBJECTS; AMPHOTERICIN-B; ITRACONAZOLE; BIOAVAILABILITY; VORICONAZOLE; FLUCONAZOLE; ABSORPTION AB The pharmacokinetics of posaconazole oral suspension in neutropenic patients undergoing high-dose chemotherapy and stem cell transplantation were evaluated, and the association of plasma posaconazole exposure with the presence and severity of oral mucositis was explored in this nonrandomized, open-label, parallel-group, multiple-dose pharmacokinetic study. Thirty patients were enrolled and received one of three regimens (group I, 200 mg once daily; group II, 400 mg once daily; group III, 200 mg four times daily) for the duration of neutropenia. The mean total exposure for day 1, as shown by the area under the concentration-time curve from 0 to 24 h (AUC(0-24)), was 1.96 mg center dot h/liter in group I and was 51% higher in group II and in group III. Increases in AUC(0-24) and maximum plasma concentration (C-max) in groups II and III were dose related. The AUC(0-24) and C-max values on day I were similar between groups II and III. There was interpatient variability of up to 68% in the pharmacokinetic values for our study population. Steady state was attained by days 5 to 6. Average steady-state plasma posaconazole trough values were 192, 219, and 414 ng/ml in groups I, II, and III, respectively. The AUC(0-24) and apparent oral clearance increased by increasing dose and dosing frequency. Mucositis appeared to reduce exposure but did not significantly affect mean total posaconazole exposure (AUC and C-max) at steady state (P = 0.1483). Moreover, this reduction could be overcome by increasing the total dose and dosing frequency. Posaconazole was safe and well tolerated. C1 Univ Arkansas Med Sci, Coll Pharm, Dept Pharm Practice, Little Rock, AR 72205 USA. Schering Plough Res Inst, Kenilworth, NJ USA. NIH, Clin Pharmacokinet Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Gubbins, PO (reprint author), Univ Arkansas Med Sci, Coll Pharm, Dept Pharm Practice, 4301 N Markham 522, Little Rock, AR 72205 USA. EM gubbinspaulo@uams.edu NR 15 TC 87 Z9 93 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2006 VL 50 IS 6 BP 1993 EP 1999 DI 10.1128/AAC.00157-06 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 048FE UT WOS:000237932200013 PM 16723557 ER PT J AU Didier, PJ Phillips, JN Kuebler, DJ Nasr, M Brindley, PJ Stovall, ME Bowers, LC Didier, ES AF Didier, Peter J. Phillips, Jennifer N. Kuebler, Dorothy J. Nasr, Mohamed Brindley, Paul J. Stovall, Mary E. Bowers, Lisa C. Didier, E. S. TI Antimicrosporidial activities of fumagillin, TNP-470, ovalicin, and ovalicin derivatives in vitro and in vivo SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID METHIONINE AMINOPEPTIDASE TYPE-2; ANGIOGENESIS INHIBITOR; TUMOR-GROWTH; INTESTINAL MICROSPORIDIOSIS; ENCEPHALITOZOON-CUNICULI; PCR ASSAY; AIDS; ALBENDAZOLE; MAMMALS; BIOLOGY AB Therapies for microsporidiosis in humans are limited, and fumagillin, which appears to be the most broadly effective antimicrosporidial drug, is considered to be moderately toxic. The purpose of this study was to apply an in vitro drug screening assay for Encephalitozoon intestinalis and Vittaforma corneae and an in vivo athymic mouse model of V. corneae infection to assess the efficacy of TNP-470 (a semisynthetic analogue of fumagillin), ovalicin, and eight ovalicin derivatives. TNP-470, ovalicin, and three of the ovalicin derivatives inhibited both E. intestinalis and V. corneae replication by more than 70% in vitro. Another three of the ovalicin derivatives inhibited one of the two microsporidian species by more than 70%. None of the treated athymic mice survived the V. corneae infection, but they did survive statistically significantly longer than the untreated controls after daily treatment with fumagillin administered at 5, 10, and 20 mg/kg of body weight subcutaneously (s.c.), TNP-470 administered at 20 mg/kg intraperitoneally (i.p.), or ovalicin administered at 5 mg/kg s.c. Of two ovalicin derivatives that were assessed in vivo, NSC 9665 given at 10 mg/kg i.p. daily also statistically significantly prolonged survival of the mice. No lesions associated with drug toxicity were observed in the kidneys or livers of uninfected mice treated with these drugs at the highest dose of 20 mg/kg daily. These results thus support continued studies to identify more effective fumagillin-related drugs for treating microsporidiosis. C1 Tulane Univ, Tulane Natl Primate Res Ctr, Div Microbiol, Covington, LA 70433 USA. Tulane Univ, Tulane Natl Primate Res Ctr, Div Comparat Pathol, Covington, LA 70433 USA. NIAID, Bethesda, MD 20892 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA USA. RP Didier, ES (reprint author), Tulane Univ, Tulane Natl Primate Res Ctr, Div Microbiol, 18703 Three Rivers Rd, Covington, LA 70433 USA. EM esdnda@tulane.edu FU NCRR NIH HHS [P51 RR000164, RR00164]; NIAID NIH HHS [N01-AI75327] NR 54 TC 25 Z9 32 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 2006 VL 50 IS 6 BP 2146 EP 2155 DI 10.1128/AAC.00020-06 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 048FE UT WOS:000237932200033 PM 16723577 ER PT J AU Pfutzner, W Joari, MR Foster, RA Vogel, JC AF Pfutzner, W Joari, MR Foster, RA Vogel, JC TI A large preclinical animal model to assess ex vivo skin gene therapy applications SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE keratinocytes; retroviral vector; ex vivo transduction; grafting; pig ID EPIDERMAL-GROWTH-FACTOR; PORCINE KERATINOCYTES; TRANSGENE EXPRESSION; MULTIDRUG-RESISTANCE; WOUND REPAIR; IN-VIVO; RETROVIRUS; CELLS; CULTURE; VIRUS AB Because of its easy accessibility, the skin is a very attractive target for gene therapy purposes. To study potential clinical applications in a preclinical setting, appropriate animal models are needed. Pig skin is very similar to human skin, and a variety of human diseases that are potentially amenable to gene therapy applications also occur in pigs. Only a few studies have analyzed the engraftment of transduced keratinocytes (KC) in pigs, however, with limited success. We describe a porcine model in which pig KC were transduced ex vivo with a retroviral vector encoding a marker gene and subsequently grafted onto the autologous host, utilizing a relatively simple grafting technique. Enhanced transduction efficiency was achieved by an optimized transduction protocol including centrifugation of the retroviral vector at a temperature of 32 degrees C. Transduced KC were then seeded onto acellular dermis, forming a stratified epidermis. Grafting was performed by creating full thickness wounds and placing the skin graft onto the muscle fascia, covered by a protective skin flap for several days. Successful engraftment of transduced KC was demonstrated by immunohistochemistry of biopsies taken at different time points, showing transgene expression in 40-50% of grafted KC. After 4 weeks, KC expressing a foreign marker gene was lost, suggesting a transgene-specific immune response in the immunocompetent pigs and highlighting the potential problems for clinical gene therapy studies when transferring new genetic material into a patient. The model presented here may be used to examine applications of skin gene therapy, where retroviral vectors encoding endogenous pig genes will be expressed in the skin. C1 Univ Munich, Dermatol Klin, D-08337 Munich, Germany. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Pfutzner, W (reprint author), Univ Munich, Dermatol Klin, Frauenlobstr 9-11, D-08337 Munich, Germany. EM Wolfgang_Pfutzner@web.de NR 39 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD JUN PY 2006 VL 298 IS 1 BP 16 EP 22 DI 10.1007/s00403-006-0653-5 PG 7 WC Dermatology SC Dermatology GA 042BB UT WOS:000237501000003 PM 16565820 ER PT J AU Olfson, M Blanco, C Liu, LX Moreno, C Laje, G AF Olfson, M Blanco, C Liu, LX Moreno, C Laje, G TI National trends in the outpatient treatment of children and adolescents with antipsychotic drugs SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PRIVATELY INSURED POPULATION; MENTAL-HEALTH UTILIZATION; DOUBLE-BLIND; PSYCHOTROPIC MEDICATIONS; TOURETTE-SYNDROME; ATYPICAL ANTIPSYCHOTICS; TIC DISORDERS; BIPOLAR-I; RISPERIDONE AB Context: Although there are indications that antipsychotic drugs are increasingly used to treat children and adolescents, little is known about the characteristics of those who receive them. Objective: To examine national trends and patterns in antipsychotic treatment of youth seen by physicians in office-based medical practice. Design: Analysis of national trends of visits (1993-2002) that included prescription of antipsychotics, and comparison of the clinical and demographic characteristics of visits (2000-2002) that included or did not include antipsychotic treatment. Setting: Outpatient visits to physicians in office-based practice. Participants: Patient visits by persons 20 years and younger from the National Ambulatory Medical Care Surveys from 1993 to 2002. Main Outcome Measures: Visits that included prescription of antipsychotics. Results: In the United States, the estimated number of office-based visits by youth that included antipsychotic treatment increased from approximately 201 000 in 1993 to 1 224 000 in 2002. From 2000 to 2002, the number of visits that included antipsychotic treatment was significantly higher for male youth (1913 visits per 100 000 population) than for female youth (739 visits per 100 000 population), and for white non-Hispanic youth (1515 visits per 100 000 population) than for youth of other racial or ethnic groups (426 visits per 100 000 population). Overall, 9.2% of mental health visits and 18.3% of visits to psychiatrists included antipsychotic treatment. From 2000 to 2002, 92.3% of visits with prescription of an antipsychotic included a second-generation medication. Mental health visits with prescription of an antipsychotic included patients with diagnoses of disruptive behavior disorders (37.8%), mood disorders (31.8%), pervasive developmental disorders or mental retardation (17.3%), and psychotic disorders (14.2%). Conclusions: There has been a sharp national increase in antipsychotic treatment among children and adolescents in office-based medical practice. Second-generation antipsychotics are being widely prescribed, and emerging empirical evidence provides a base of support that is limited to short-term safety and efficacy. C1 Columbia Univ Coll Phys & Surg, Dept Psychiat, Mailman Sch Publ Hlth, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Mailman Sch Publ Hlth, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. NIMH, Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Olfson, M (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, Mailman Sch Publ Hlth, 1051 Riverside Dr, New York, NY 10032 USA. EM mo49@columbia.edu RI Blanco, Carlos/I-4906-2013; Laje, Gonzalo/L-2654-2014 OI Blanco, Carlos/0000-0001-6187-3057; Laje, Gonzalo/0000-0003-2763-3329 FU NIDA NIH HHS [DA015559, DA00482]; NIMHD NIH HHS [MD000206] NR 45 TC 328 Z9 332 U1 6 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2006 VL 63 IS 6 BP 679 EP 685 DI 10.1001/archpsyc.63.6.679 PG 7 WC Psychiatry SC Psychiatry GA 049XD UT WOS:000238050200010 PM 16754841 ER PT J AU Lord, C Risi, S DiLavore, PS Shulman, C Thurm, A Pickles, A AF Lord, C Risi, S DiLavore, PS Shulman, C Thurm, A Pickles, A TI Autism from 2 to 9 years of age SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC OBSERVATION SCHEDULE; PERVASIVE DEVELOPMENTAL DISORDERS; BEHAVIORAL TREATMENT; SPECTRUM DISORDERS; SOCIAL-BEHAVIOR; FIELD TRIAL; FOLLOW-UP; DSM-IV; CHILDREN; ABNORMALITIES AB Context: Autism represents an unusual pattern of development beginning in the infant and toddler years. Objectives: To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. Design: Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview-Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. Setting: Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. Participants: At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. Main Outcome Measures: Consensus best-estimate diagnoses at 9 years of age. Results: Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted kappa of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ (P = .001) was taken into account at age 2 years, the ADI-R repetitive domain (P = .02) and the ADOS social (P = .05) and repetitive domains (P = .005) significantly predicted autism at age 9 years. Conclusions: Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation. C1 Univ Michigan, Autism & Commun Disorders Ctr, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC USA. Hebrew Univ Jerusalem, Jerusalem, Israel. NIMH, Bethesda, MD 20892 USA. Univ Manchester, Manchester, Lancs, England. RP Lord, C (reprint author), Univ Michigan, Autism & Commun Disorders Ctr, 1111 E Catherine St, Ann Arbor, MI 48109 USA. EM celord@umich.edu RI Pickles, Andrew/A-9625-2011 OI Pickles, Andrew/0000-0003-1283-0346 FU NICHD NIH HHS [P01 HD035482, HD 35482-01]; NIMH NIH HHS [MH066469, MH57167, R01 MH066496, R25 MH057167] NR 36 TC 339 Z9 346 U1 13 U2 60 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUN PY 2006 VL 63 IS 6 BP 694 EP 701 DI 10.1001/archpsyc.63.6.694 PG 8 WC Psychiatry SC Psychiatry GA 049XD UT WOS:000238050200012 PM 16754843 ER PT J AU Nishiwaki, M Ikewaki, K Bader, G Nazih, H Hannuksela, M Remaley, AT Shamburek, RD Brewer, HB AF Nishiwaki, M Ikewaki, K Bader, G Nazih, H Hannuksela, M Remaley, AT Shamburek, RD Brewer, HB TI Human lecithin: Cholesterol acyltransferase deficiency - In vivo kinetics of low-density lipoprotein and lipoprotein-X SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lecithin; cholesterol acyltransferase; low-density lipoprotein; lipoprotein-X; kinetics; stable isotope ID APOLIPOPROTEIN-A-I; PERFUSED RAT-LIVER; FAMILIAL LECITHIN; PLASMA LIPOPROTEINS; LCAT DEFICIENCY; METABOLISM; DISEASE AB Objectives - Lecithin:cholesterol acyltransferase deficiency (LCAT-def) is characterized by low levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) and the accumulation of lipoprotein-X (LpX). Despite the low HDL, atherosclerosis is uncommon in LCAT-def. The decreased LDL would be a possible explanation but the underlying mechanism is not clear. In addition, the mechanism(s) for LpX accumulation is not known. The aim of the present study is to elucidate the mechanism(s) responsible for the low LDL and determine the plasma kinetics of LpX in LCAT-def. Methods and Results - We conducted a radiotracer study in LCAT-def (n = 2) and normal controls (n = 10) and a stable isotope study in one patient and other controls (n = 7). LCAT-def LDL was catabolized faster than control LDL in the control subjects as well as in LCAT-def patients. Control LDL was catabolized faster in LCAT- def patients than the controls. The production rate of LDL apolipoprotein B-100 was normal in LCAT-def. The increased LDL apoB-100 catabolism was confirmed by a stable isotope study. LpX was catabolized more slowly in LCAT-def. Conclusions - The decreased LDL in LCAT-def is attributable to an increased catabolism caused by a rapid catabolism of abnormal LDL and an upregulation of LDL receptor pathway. The decreased catabolism of LpX contributes to its accumulation in LCAT-def. C1 Natl Def Med Coll, Dept Internal Med 1, Tokorozawa, Saitama 3598513, Japan. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Jikei Univ, Sch Med, Dept Internal Med, Div Cardiol, Tokyo, Japan. RP Nishiwaki, M (reprint author), Natl Def Med Coll, Dept Internal Med 1, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. EM masato@hi-ho.ne.jp NR 23 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2006 VL 26 IS 6 BP 1370 EP 1375 DI 10.1161/01.ATV.0000217910.90210.99 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 044AI UT WOS:000237644000029 PM 16543491 ER PT J AU Kathiresan, S Yang, Q Larson, MG Camargo, AL Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ AF Kathiresan, S Yang, Q Larson, MG Camargo, AL Tofler, GH Hirschhorn, JN Gabriel, SB O'Donnell, CJ TI Common genetic variation in five thrombosis genes and relations to plasma hemostatic protein level and cardiovascular disease risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coagulation; fibrinogen; genetics; myocardial infarction; plasminogen activators; thrombosis; polymorphism ID CORONARY-HEART-DISEASE; PLASMINOGEN-ACTIVATOR GENE; ENHANCER POLYMORPHISM; HUMAN GENOME; RETINOIC ACID; ASSOCIATION; FIBRINOGEN; IDENTIFICATION; PROMOTER; REGION AB Objective - We undertook a linkage disequilibrium (LD) - based genetic approach to investigate the hypothesis that common sequence variants in 5 thrombosis genes influence plasma hemostatic protein levels or risk of cardiovascular disease (CVD). Methods and Results - In a reference panel, we characterized LD structure at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart Study participants. There were significant associations of 9 FGB SNPs with fibrinogen level (minimum P = 0.002) and of 7 F7 SNPs and factor VII level (minimum P < 0.0001). SNPs at the PLAT locus were not associated with PLAT level. In stepwise analysis, a single FGB variant explained 1% of the residual variance in fibrinogen level, and 2 F7 SNPs together explained 10% of the residual variance in factor VII level. Two PLAT haplotypes were associated with CVD (multivariable-adjusted global P = 0.0004). Conclusions - A comprehensive survey of common sequence variation demonstrates that cis-regulatory SNPs explain a modest proportion of the residual variance in circulating fibrinogen and factor VII level and PLAT haplotypes increase the risk of CVD. Additional studies are warranted to confirm the association of PLAT sequence variation and risk of CVD. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Harvard Univ, Sch Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Endocrinol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [HL66582, N01-HC-25195] NR 39 TC 45 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2006 VL 26 IS 6 BP 1405 EP 1412 DI 10.1161/01.ATV.0000222011.13026.25 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 044AI UT WOS:000237644000034 PM 16614319 ER PT J AU Neogi, T Nevitt, M Niu, J LaValley, MP Hunter, DJ Terkeltaub, R Carbone, L Chen, H Harris, T Kwoh, K Guermazi, A Felson, DT AF Neogi, T Nevitt, M Niu, J LaValley, MP Hunter, DJ Terkeltaub, R Carbone, L Chen, H Harris, T Kwoh, K Guermazi, A Felson, DT TI Lack of association between chondrocalcinosis and increased risk of cartilage loss in knees with osteoarthritis - Results of two prospective longitudinal magnetic resonance imaging studies SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DIHYDRATE CRYSTAL-DEPOSITION; JOINT-SPACE WIDTH; OSTEO-ARTHRITIS; PYROPHOSPHATE; DISEASE; PREVALENCE; EXPRESSION; DIFFERENTIATION; REPRODUCIBILITY; PROGRESSION AB Objective. To evaluate the relationship between chondrocalcinosis and the progression of knee osteoarthritis (OA) using longitudinal magnetic resonance imaging (MRI) assessments. Methods. Longitudinal knee MRIs were obtained in the Boston OA Knee Study (BOKS) and in the Health, Aging and Body Composition (Health ABC) Study. Chondrocalcinosis was determined as present or absent on baseline knee radiographs. Cartilage morphology was graded on paired longitudinal MRIs using the Whole-Organ Magnetic Resonance Imaging Score in 5 cartilage subregions of each of the medial and lateral tibiofemoral joints. Cartilage loss in a subregion was defined as an increase in the cartilage score of >= 1 (0-4 scale). The risk for change in the number of subregions with cartilage loss was assessed using Poisson regression, with generalized estimating equations to account for correlations. Analyses were adjusted for age, sex, body mass index, baseline cartilage score, and presence of damaged menisci. Results. In BOKS, 23 of the 265 included knees (9%) had chondrocalcinosis. In Health ABC, 373 knees were included, of which 69 knees (18.5%) had chondrocalcinosis. In BOKS, knees with chondrocalcinosis had a lower risk of cartilage loss compared with knees without chondrocalcinosis (adjusted risk ratio [RR] 0.4, 95% confidence interval [95% CI] 0.2-0.7) (P = 0.002), and there was no difference in risk in Health ABC (adjusted RR 0.9, 95% CI 0.6-1.5) (P = 0.7). Stratification by intact versus damaged menisci produced similar results within each cohort. Conclusion. In knees with OA, the presence of chondrocalcinosis was not associated with increased cartilage loss. These findings do not support the hypothesis that chondrocalcinosis worsens OA progression. C1 Boston Univ, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif San Diego, San Diego, CA 92103 USA. VAMC, San Diego, CA USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Intramural Res Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Osteoporosis & Arthritis Res Grp, San Francisco, CA USA. RP Neogi, T (reprint author), Boston Univ, Clin Epidemiol Res & Training Unit, 715 Albany St,A203, Boston, MA 02118 USA. EM tneogi@bu.edu RI Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Felson, David/0000-0002-2668-2447; Niu, Jingbo/0000-0002-6170-1965; Neogi, Tuhina/0000-0002-9515-1711; LaValley, Michael/0000-0002-8488-5170 FU NIA NIH HHS [AG-07996, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIAMS NIH HHS [AR-47785] NR 43 TC 38 Z9 41 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2006 VL 54 IS 6 BP 1822 EP 1828 DI 10.1002/art.21903 PG 7 WC Rheumatology SC Rheumatology GA 052AT UT WOS:000238203600014 PM 16729275 ER PT J AU Liossis, SNC Solomou, EE Sfikakis, PP AF Liossis, SNC Solomou, EE Sfikakis, PP TI Lyn dericiency in B cells from patients with systemic lupus erythematosus: comment on the article by Flores-Borja et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID DISEASE-ACTIVITY; EXPRESSION; INDEX C1 Univ Patras, Sch Med, GR-26110 Patras, Greece. NIH, Bethesda, MD 20892 USA. Natl Univ Athens, Sch Med, Athens, Greece. RP Liossis, SNC (reprint author), Univ Patras, Sch Med, GR-26110 Patras, Greece. NR 7 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 2006 VL 54 IS 6 BP 2036 EP 2037 DI 10.1002/art.21878 PG 2 WC Rheumatology SC Rheumatology GA 052AT UT WOS:000238203600048 PM 16732577 ER PT J AU Askari, H Kleiner, D Kaneski, C Spollen, L Schiffmann, R AF Askari, H. Kleiner, D. Kaneski, C. Spollen, L. Schiffmann, R. TI Cellular and tissue distribution of globotriaosylceramide (Gb3) in fabry disease (FD) SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NINDS, NIH, Metab Neurol, Bethesda, MD 20892 USA. NINDS, NIH, Dept Pathol, Bethesda, MD 20892 USA. Univ Missouri, Columbia Hosp & clin, Dept Pathol, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 237 EP 237 DI 10.1016/S1567-5688(06)80943-8 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093901353 ER PT J AU Bocharov, A Eggerman, T AF Bocharov, A. Eggerman, T. TI Targeting of scavenger receptor class B type I by synthetic amphipathic helical containing peptides blocks LPS uptake and LPS-induced proinflammator SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 MA WeW328 BP 310 EP 310 DI 10.1016/S1567-5688(06)81246-8 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093902028 ER PT J AU Remaley, AT Stonik, J Fairwel, T Demosky, S Neufeld, EB Brewer, HB AF Remaley, A. T. Stonik, J. Fairwel, T. Demosky, S. Neufeld, E. B. Brewer, H. B. TI The role of various structural motifs of HDL-mimetic peptides in cholesterol efflux by the ABCA1 transporter SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NHLBI, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 MA WeW381 BP 320 EP 320 DI 10.1016/S1567-5688(06)81281-X PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093902063 ER PT J AU Potenza, MA Marasciulo, FL Tarquinio, M Tiravanti, E Colantuono, G Federici, A Quon, MJ Montagnani, M AF Potenza, M. A. Marasciulo, F. L. Tarquinio, M. Tiravanti, E. Colantuono, G. Federici, A. Quon, M. J. Montagnani, M. TI Epigallocatechin gallate reduces blood pressure, improves insulin sensitivity, and protects against myocardial ischemia/reperfusion injury in SHR SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 Univ Bari, Bari, Italy. NIH, Diabet Unit, NCCAM, Bethesda, MD USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 454 EP 454 DI 10.1016/S1567-5688(06)81838-6 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903059 ER PT J AU Zuliani, G Galvani, M Bandinelli, S Corsi, AM Lauretani, F Fellin, R Ferrucci, L AF Zuliani, G. Galvani, M. Bandinelli, S. Corsi, A. M. Lauretani, F. Fellin, R. Ferrucci, L. TI Factors associated with elevated C reactive protein levels in older individuals with and without metabolic syndrome SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 Univ Ferrara, Dept Clin & Expt Med, Ferrara, Italy. Asf Geriatr Rehabil, Florence, Italy. Tuscany Reg Hlth Agcy, Florence, Italy. Ars Tuscany, Florence, Italy. NIA, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 471 EP 471 DI 10.1016/S1567-5688(06)81889-1 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903110 ER PT J AU Gori, AM Corsi, AM Bandinelli, S Giusti, B Lauretani, F Saracini, C Sestini, I Ferrucci, L Abbate, R Gensini, GF AF Gori, A. M. Corsi, A. M. Bandinelli, S. Giusti, B. Lauretani, F. Saracini, C. Sestini, I. Ferrucci, L. Abbate, R. Gensini, G. F. TI Determinants for vitamin B6 and folate concentrations in elderly: The Inchianti study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 Univ Florence, Az Osped Univ Careggi, Dept Med, Thrombosis Ctr, I-50121 Florence, Italy. Univ Florence, Az Osped Univ Careggi, Surg Crit Area, Thrombosis Ctr, I-50121 Florence, Italy. Natl Inst Res & Care Aging, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. NIA, Longitudinal Studies Sect, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 480 EP 480 DI 10.1016/S1567-5688(06)81919-7 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903140 ER PT J AU Basso, F Freeman, L Ko, C Tansey, T Amar, MJ Thomas, F Santamarina-Fojo, S Brewer, HB AF Basso, F. Freeman, L. Ko, C. Tansey, T. Amar, M. J. Thomas, F. Santamarina-Fojo, S. Brewer, H. B. TI Decreased plasma APOB-containing lipoprotein and atherosclerosis in ABCG5/G8 x LDLr-KO mice on ezetimibe SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 482 EP 482 DI 10.1016/S1567-5688(06)81926-4 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903147 ER PT J AU Howard, BV Rossouw, J Anderson, G Manson, JE Hsia, J Wassertheil-Smoller, S Hendrix, S Chlebowski, R Stefanick, ML Cauley, J Jackson, R AF Howard, B. V. Rossouw, J. Anderson, G. Manson, J. E. Hsia, J. Wassertheil-Smoller, S. Hendrix, S. Chlebowski, R. Stefanick, M. L. Cauley, J. Jackson, R. TI Postmenopausal hormone therapy - Lessons from the women's health initiative SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN C1 MedStar Res Inst, Hyattsville, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Brigham & Womens Hosp, Chestnut Hill, MA USA. George Washington Univ, Washington, DC 20052 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Wayne State Univ, Detroit, MI 48202 USA. Harbor UCLA Res & Educ Inst, Torrance, CA USA. Stanford Univ, San Jose, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Ohio State Univ, Columbus, OH 43210 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 485 EP 485 DI 10.1016/S1567-5688(06)81936-7 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903157 ER PT J AU Kruth, H Zhao, B Buono, C Li, Y Waldo, S Jones, N AF Kruth, H. Zhao, B. Buono, C. Li, Y. Waldo, S. Jones, N. TI Macrophage foam cell formation mediated by receptor-independent macropinocytosis of native LDL SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 515 EP 515 DI 10.1016/S1567-5688(06)82060-X PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903281 ER PT J AU Vishnyakova, TG Patterson, AP AF Vishnyakova, T. G. Patterson, A. P. TI CLA-1 and its splicing variant CLA-2 mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 517 EP 517 DI 10.1016/S1567-5688(06)82069-6 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903290 ER PT J AU Vigna, GB Volpato, S Zuliani, G Bandinelli, S Corsi, AM Lauretani, F Fellin, R Guralnik, JM Ferrucci, L AF Vigna, G. B. Volpato, S. Zuliani, G. Bandinelli, S. Corsi, A. M. Lauretani, F. Fellin, R. Guralnik, J. M. Ferrucci, L. TI Lipoprotein(a) and peripheral arterial disease by ankle/brachial index: Data from the InChianti Study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Incra, Lab Clin Epidemiol, Florence, Italy. NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. NIA, NIH, Long Studies Sect, Cl Res Branch, Bethesda, MD 20892 USA. RI Vigna, Giovanni/H-2826-2015 OI Vigna, Giovanni/0000-0001-8640-7052 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 530 EP 530 DI 10.1016/S1567-5688(06)82131-8 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903352 ER PT J AU Zuliani, G Volpato, S Ble', A Bandinelli, S Corsi, AM Lauretani, F Paolisso, G Fellin, R Ferrucci, L AF Zuliani, G. Volpato, S. Ble', A. Bandinelli, S. Corsi, A. M. Lauretani, F. Paolisso, G. Fellin, R. Ferrucci, L. TI High interleukin-6 plasma levels are associated with low high-density lipoprotein cholesterol in community-dwelling older adults: The InChianti study SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 14th Meeting of the International-Society-of-Atherosclerosis CY JUN 18-22, 2006 CL Rome, ITALY SP Int Soc Atheroscleros C1 Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Asf Geriatr Rehabil, Florence, Italy. IOT, Tuscany Reg Hlth Agcy, Florence, Italy. Ars Tuscany, Florence, Italy. Dept Geriatr Med & Metab Dis Vi, Naples, Italy. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD JUN PY 2006 VL 7 IS 3 BP 534 EP 534 DI 10.1016/S1567-5688(06)82148-3 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064MN UT WOS:000239093903369 ER PT J AU Prieto, P Baird, AW Blaauboer, BJ Ripoll, JVC Corvi, R Dekant, W Dietl, P Gennari, A Gribaldo, L Griffin, JL Hartung, T Heindel, JJ Hoet, P Jennings, P Marocchio, L Noraberg, J Pazos, P Westmoreland, C Wolf, A Wright, J Pfaller, W AF Prieto, Pilar Baird, Alan W. Blaauboer, Bas J. Ripoll, Jose Vicente Castell Corvi, Raffaella Dekant, Wolfgang Dietl, Paul Gennari, Alessandra Gribaldo, Laura Griffin, Julian L. Hartung, Thomas Heindel, Jerry J. Hoet, Peter Jennings, Paul Marocchio, Luciana Noraberg, Jens Pazos, Patricia Westmoreland, Carl Wolf, Armin Wright, Jayne Pfaller, Walter TI The assessment of repeated dose toxicity in vitro: A proposed approach - The report and recommendations of ECVAM workshop 56 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Review ID BLOOD-BRAIN-BARRIER; NOMINAL EFFECTIVE CONCENTRATIONS; HIPPOCAMPAL SLICE CULTURES; AIR PARTITION-COEFFICIENTS; COLONY-FORMING CELLS; ORGANIC-CHEMICALS; PHARMACOKINETIC MODELS; RISK-ASSESSMENT; TASK-FORCE; CYTOTOXIC CONCENTRATIONS AB This is the 56th report of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). The main goal of ECVAM, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which have scientific relevance and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures that would enable it to become well informed about the state-of-the-art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would be best achieved by the organisation of ECVAM workshops on specific topics, at which focused groups of invited experts would review the current status of non animal-based tests and their potential uses, and make recommendations about the best ways forward (1). The ECVAM workshop on repeated dose toxicity in vitro was held on 15-17 September 2004, at ECVAM in Ispra, Italy. The workshop was chaired by Walter Pfaller and Pilar Prieto, and was attended by pharmacologists and toxicologists from academia, industry and government, from different research backgrounds and with different ways of thinking. The main goal was to discuss and evaluate alternative approaches to In vivo repeated dose toxicity testing. C1 Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. Natl Univ Ireland Univ Coll Dublin, Dublin 4, Ireland. Univ Utrecht, IRAS, Utrecht, Netherlands. Hosp La Fe, Res Ctr, E-46009 Valencia, Spain. Univ Wurzburg, Inst Toxicol, D-8700 Wurzburg, Germany. Univ Ulm, Dept Physiol, Ulm, Germany. Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. Catholic Univ Louvain, Pneumol Lab, B-3000 Louvain, Belgium. Innsbruck Med Univ, Div Physiol, Dept Physiol & Med Phys, Innsbruck, Austria. GSK Safety Assessment, Ware, Herts, England. Univ So Denmark, Med Biol Inst, Odense, Denmark. Unilever, Safety & Environm Assurance Ctr, Sharnbrook, Beds, England. Novartis Pharma AG, Biomarker Dev, Basel, Switzerland. Syngenta CTL, Macclesfield, Cheshire, England. RP Prieto, P (reprint author), Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, TP 580, I-21020 Ispra, VA, Italy. RI pfaller, walter/A-8803-2010; Jennings, Paul/A-8670-2010; Hoet, Peter/H-9987-2013 OI Jennings, Paul/0000-0002-6860-2898; Hoet, Peter/0000-0002-0292-6603 NR 141 TC 33 Z9 33 U1 0 U2 2 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD JUN PY 2006 VL 34 IS 3 BP 315 EP 341 PG 27 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 063TG UT WOS:000239042000009 PM 16831063 ER PT J AU Katz, JL Kopajtic, TA Terry, P AF Katz, Jonathan L. Kopajtic, Theresa A. Terry, Philip TI Effects of dopamine D1-like receptor agonists on food-maintained operant behavior in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE dopamine agonists; D1-like receptors; operant behavior; schedule-controlled behavior; 5-HT antagonists; 5-HT2 receptors; rat ID SCHEDULE-CONTROLLED BEHAVIOR; FEEDING-BEHAVIOR; SQUIRREL-MONKEY; SEROTONIN(2C) RECEPTORS; D-1-DOPAMINE RECEPTORS; D1-RECEPTOR AGONISTS; ADENYLATE-CYCLASE; XENOPUS OOCYTES; D-1 AGONISTS; D1 AGONISTS AB The effects on learned operant behavior of agonist actions at dopamine D1-like receptors have not been fully characterized. We compared three D1-like receptor agonists (SKF 38393, SKF 77434 and SKF 82958), both alone and in combination with the D1-like receptor antagonist, SCH 23390. Binding affinities for the agonists at dopamine D1 receptors from rat striatum membranes were determined and compared with effects on behavior. Lever pressing was maintained by food reinforcement under a fixed-ratio 30-response schedule (each 30th response produced reinforcement), and the effects of the three agonists were assessed by cumulative dosing. Each drug produced dose-related reductions in response rates, with an order of potency (SKF 82958 > SKF 77434 > SKF 38393) that agreed with rank order of binding affinities. Antagonism of these behavioral effects by SCH 23390 only significant for SKF 82958; surprisingly, SCH 23390 enhanced the effects of SKF 38393. For SKF 82958, the antagonism was receptor subtype-specific, as the D2-like receptor antagonist spiperone was ineffective. The nonselective serotonergic antagonist metergoline produced a significant rightward shift of the SKF 38393 dose-response function, indicating effective antagonism, although the degree of antagonism was not dose-related. These results support the view that the behavioral effects of D1-like receptor agonists differ in their susceptibility to antagonism by D1-like receptor antagonists, and that some effects of SKF 38393 may be mediated by serotonergic activity rather than by activity at D1-like receptors. C1 Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), Natl Inst Drug Abuse, Psychobiol Sect, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 NR 46 TC 4 Z9 4 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD JUN PY 2006 VL 17 IS 4 BP 303 EP 309 DI 10.1097/01.fbp.0000205015.67079.f7 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 066LN UT WOS:000239231200002 PM 16914948 ER PT J AU Kaur, G Hollingshead, M Holbeck, S Schauer-Vukasinovic, V Camalier, RF Domling, A Agarwal, S AF Kaur, G Hollingshead, M Holbeck, S Schauer-Vukasinovic, V Camalier, RF Domling, A Agarwal, S TI Biological evaluation of tubulysin A: a potential anticancer and antiangiogenic natural product SO BIOCHEMICAL JOURNAL LA English DT Article DE antiangiogenesis; anticancer agent; cytochrome P450; microtubule; tubulin; tubulysin A ID INSTITUTE DRUG SCREEN; TUMOR-CELL-LINES; IN-VIVO; TUBULIN POLYMERIZATION; HOLLOW FIBERS; CANCER; ANGIOGENESIS; MICROTUBULES; RESISTANCE; MYXOBACTERIA AB Tubulysin A (tubA) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. The potential of tubA as an anticancer and antiangiogenic agent is explored in the present study. tubA shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. It induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic properties in several in vitro assays. It is efficacious in initial animal studies using a hollow fibre assay with 12 different human tumour cell lines. This study suggests that both in vitro and preclinical profiles of tubA may translate into clinically useful anticancer properties. C1 NCI, DCTD, Dev Therapeut Program, Bethesda, MD 20892 USA. Morphochem Inc, Monmouth Jct, NJ 08852 USA. Morphochem AG, D-81379 Munich, Germany. RP Agarwal, S (reprint author), Yale Univ, Yale Comprehens Canc Ctr, Sch Med, 333 Cedar St, New Haven, CT 06520 USA. EM seema.agarwal@yale.edu FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 40 TC 75 Z9 75 U1 1 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2006 VL 396 BP 235 EP 242 DI 10.1042/BJ20051735 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 052NP UT WOS:000238240700005 PM 16489930 ER PT J AU Raychaudhuri, S Prinz, WA AF Raychaudhuri, S Prinz, WA TI Uptake and trafficking of exogenous sterols in Saccharomyces cerevisiae SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Biochemical-Society Focused Meeting CY DEC 15-16, 2005 CL Goodenough Coll, London, ENGLAND SP Biochem Soc HO Goodenough Coll DE ATP-binding-cassette transporter (ABC transporter); endoplasmic reticulum; exogenous sterol; oxysterol-binding protein; Saccharomyces cerevisiae; sterol trafficking ID OXYSTEROL-BINDING-PROTEIN; INTRACELLULAR CHOLESTEROL TRANSPORT; CASSETTE ABC TRANSPORTERS; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; LIPID-METABOLISM; YEAST; SPHINGOMYELIN; HOMOLOGS; SUPERFAMILY AB The proper distribution of sterols among organelles is critical for numerous cellular functions. How sterols are sorted and moved among membranes remains poorly understood, but they are transported not only in vesicles but also by non-vesicular pathways. one of these pathways moves exogenous sterols from the plasma membrane to the endoplasmic reticulum in the yeast Saccharomyces cerevisiae. we have found that two classes of proteins play critical roles in this transport, ABC transporters (ATP-binding-cassette transporters) and oxysterol-binding protein-related proteins. Transport is also regulated by phosphoinositides and the interactions of sterols with other lipids. Here, we summarize these findings and speculate on the role of non-vesicular sterol transfer in determining intracellular sterol distribution and membrane function. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Prinz, WA (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM wprinz@helix.nih.gov OI Raychaudhuri, Sumana/0000-0002-3164-0057 FU Intramural NIH HHS NR 35 TC 12 Z9 13 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD JUN PY 2006 VL 34 BP 359 EP 362 PN 3 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 057YB UT WOS:000238630000007 PM 16709161 ER PT J AU Teng, CT AF Teng, Christina T. TI Factors regulating lactoferrin gene expression SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 7th International Conference on Lactoferrin CY OCT 16-19, 2005 CL Waikiki Beach, HI SP A O C E Inst, Belgo Milk, DMV Int, Fonterra, Four Leaf Japan Co Ltd, Jarow Formulas, Mead Johnson Nutr, MG Nutr, Morinaga Milk Co, NRL Pharma, Pharming, Ventria Biosci, Wyeth-Ayerst Int DE lactoferrin; regulation; transcription factors; nuclear receptors ID CCAAT DISPLACEMENT PROTEIN; ESTROGEN RESPONSE ELEMENT; C/EBP-EPSILON; REPRODUCTIVE-TRACT; RETINOIC ACID; MYELOID DIFFERENTIATION; TRANSCRIPTION FACTORS; NUCLEAR RECEPTORS; BINDING PROTEINS; MAMMARY-GLAND AB Regulation of gene expression by nuclear receptors and transcription factors involves the concerted action of multiple proteins. The process of transcriptional activation involves chromatin modification, nuclear receptor or transcription factor binding to the response element of the promoter, and coregulator recruitment. Despite advances in knowledge pertaining to the molecular mechanisms of gene regulation overall, there is very limited information available on the molecular mechanism of lactoferrin gene regulation. This review will outline novel information relating to general gene regulation and will discuss the current understanding of the regulation of lactoferrin gene expression by nuclear receptors and transcription factors. C1 Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, 111 TW Alexander Dr,POB 12233,E2-01, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov NR 48 TC 20 Z9 21 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD JUN PY 2006 VL 84 IS 3 BP 263 EP 267 DI 10.1139/006-034 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077TB UT WOS:000240052000001 PM 16936795 ER PT J AU Teng, CT Gladwell, W AF Teng, Christina T. Gladwell, Wesley TI Single nucleotide polymorphisms (SNPs) in human lactoferrin gene SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Article; Proceedings Paper CT 7th International Conference on Lactoferrin CY OCT 16-19, 2005 CL Waikiki Beach, HI SP A O C E Inst, Belgo Milk, DMV Int, Fonterra, Four Leaf Japan Co Ltd, Jarow Formulas, Mead Johnson Nutr, MG Nutr, Morinaga Milk Co, NRL Pharma, Pharming, Ventria Biosci, Wyeth-Ayerst Int DE lactoferrin gene; single nucleotide polymorphism (SNP) ID PERIODONTITIS AB The lactoferrin protein possesses antimicrobial and antiviral activities. It is also involved in the modulation of the immune response. In a normal healthy individual, lactoferrin plays a role in the front-line host defense against infection and in immune and inflammatory responses. Whether genomic variations, such as single nucleotide polymorphisms (SNPs), have an effect on the structure and function of lactoferrin protein and whether these variations contribute to the different susceptibility of individuals in response to environmental insults are interesting health-related issues. In this study, the lactoferrin gene was resequenced as part of the Environmental Genome Project of the National Institute of Environmental Health Sciences, which operates within the National Institutes of Health. Ninety-one healthy donors of different ethnicities were used to establish common SNPs in the exons of the lactoferrin gene in the general population. The data will serve as a basis from which study the association of lactoferrin polymorphism and disease. C1 Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), Natl Inst Environm Hlth Sci, Gene Regulat Sect, Reprod & Dev Toxicol Lab, NIH, 111 TW Alexander,POB 12233, Res Triangle Pk, NC 27709 USA. EM teng1@niehs.nih.gov NR 7 TC 14 Z9 15 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD JUN PY 2006 VL 84 IS 3 BP 381 EP 384 DI 10.1139/006-035 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077TB UT WOS:000240052000017 PM 16936811 ER PT J AU Cho-Chung, YS AF Cho-Chung, Yoon S. TI Autoantibody biomarkers in the detection of cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE autoantibody-based EIA; cancer detection; biomarker; autoantibody ECPKA; cAMP-dependent protein kinase ID PROTEIN-KINASE-A; BREAST-CANCER; PROSTATE-CANCER; CIRCULATING ANTIBODIES; COLORECTAL-CANCER; TUMOR-MARKERS; SERUM; P53; ANTIGEN; ALPHA AB By definition, tumor biomarkers are selective molecules that can distinguish between patients with cancer and controls. Serum tumor markers have been the most widely used approach for cancer detection. However, the limitations of these markers, which are based on the measurement of tumor antigens, preclude their general use in cancer screening and diagnosis. Here we give an over-view of recent cancer biomarker developments based on the detection of autoantibodies produced against tumor antigens in patients' sera. This new detection method can measure the autoantibodies for a spectrum of tumor antigens in a single assay, with sensitivity and specificity exceeding those obtained using the conventional antigen determination method. Autoantibodies against serum cancer biomarkers offer a novel technology for cancer detection. Published by Elsevier B.V. C1 NCI, Cellular Biochem Sect, Basic Res Lab, CCR, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Basic Res Lab, CCR, Bldg 10,Room 5B05,9000 Rockville Pik, Bethesda, MD 20892 USA. EM yc12b@nih.tov FU Intramural NIH HHS NR 34 TC 33 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JUN PY 2006 VL 1762 IS 6 BP 587 EP 591 DI 10.1016/j.bbadis.2006.04.001 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 063UG UT WOS:000239044800002 PM 16730166 ER PT J AU Coumoul, X Deng, CX AF Coumoul, Xavier Deng, Chu-Xia TI RNAi in mice: a promising approach to decipher gene functions in vivo SO BIOCHIMIE LA English DT Article DE RNAi; mice; knockdown; Cre-1oxP; Fgfr2 ID SMALL-INTERFERING-RNA; DOUBLE-STRANDED-RNA; MAMMALIAN-CELLS; CAENORHABDITIS-ELEGANS; TRANSGENIC MICE; MESSENGER-RNA; KNOCKOUT MICE; MOUSE EMBRYOS; PLASMID DNA; ADULT MICE AB RNA interference (RNAi) is a simple and powerful tool widely used to study gene functions in many species. Vector-based systems using RNA polymerase III promoters have been developed to achieve stable expression of small interfering RNA (siRNA) or small hairpin RNA (shRNA) in mammalian cells. Recent investigations demonstrated that when, combined with the Cre-loxP system, the vector-based RNAi can be used to achieve conditional or tissue specific knockdown of endogenous genes with high efficiency in mice. Here, we review these recent progresses and discuss the advantages, limitations and future development of this emerging technology. (c) 2006 Elsevier SAS. All rights reserved. C1 INSERM, UMRS 490, Unite Toxicol Mol, F-75270 Paris 06, France. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), INSERM, UMRS 490, Unite Toxicol Mol, 45,Rue St Peres, F-75270 Paris 06, France. EM xavier.coumoul@univ-paris5.fr; chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 77 TC 15 Z9 18 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD JUN PY 2006 VL 88 IS 6 BP 637 EP 643 DI 10.1016/j.biochi.2005.11.010 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 071QV UT WOS:000239617600008 PM 16426724 ER PT J AU Ingram, DK Roth, GS Lane, MA Ottinger, MA Zou, S de Cabo, R Mattison, JA AF Ingram, Donald K. Roth, George S. Lane, Mark A. Ottinger, Mary Ann Zou, Sige de Cabo, Rafael Mattison, Julie A. TI The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies SO BIOGERONTOLOGY LA English DT Editorial Material DE nutrition; aging; obesity; diabetes; cancer; heart disease; insulin; glucose; primates ID CALORIE RESTRICTION; RHESUS-MONKEYS; BODY-WEIGHT; LIFE-SPAN; MORTALITY; DISEASE; HEALTH; PRIMATES; STRATEGY AB Based on results emerging from long-term studies of dietary restriction in rhesus monkeys, we offer our views regarding whether dietary restriction can increase longevity in humans. Because lifespan data in monkeys remain inconclusive currently, we respond that "we do not for sure." Based on the vast literature regarding the effects of healthy, low calorie diets on health and longevity in a wide range of species, including humans, and based on data emerging from monkey studies suggesting that dietary restriction improves markers of disease risk and health, we respond that "we think so." Because it is unlikely that an experimental study will ever be designed to address this question in humans, we respond that "we think we will never know for sure." We suggest that debate of this question is clearly an academic exercise; thus, we would suggest that the more compelling discussion should focus on whether basic mechanisms of DR can be discovered and if such discoveries can lead to the development of effective DR mimetics. Even if proof that DR or DR mimetics can increase longevity in humans will likely never emerge, we would suggest that endpoints regarding disease risk and disease incidence as well as maintenance of function can be examined in human clinical trials, and that these will be highly relevant for evaluating the effectiveness of such treatments. C1 NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. GeroSci Inc, Pylesville, MD 21132 USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS NR 38 TC 42 Z9 42 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1389-5729 J9 BIOGERONTOLOGY JI Biogerontology PD JUN PY 2006 VL 7 IS 3 BP 143 EP 148 DI 10.1007/s10522-006-9013-2 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 085AY UT WOS:000240576700005 PM 16732404 ER PT J AU Makarova, KS Koonin, EV Haselkorn, R Galperin, MY AF Makarova, KS Koonin, EV Haselkorn, R Galperin, MY TI Cyanobacterial response regulator PatA contains a conserved N-terminal domain (PATAN) with an alpha-helical insertion SO BIOINFORMATICS LA English DT Article ID SP STRAIN PCC-7120; MYXOCOCCUS-XANTHUS; SIGNAL-TRANSDUCTION; HETEROCYST FORMATION; PATTERN-FORMATION; GLIDING MOTILITY; LOW-TEMPERATURE; GAF DOMAIN; PROTEINS; ANABAENA AB The cyanobacterium Anabaena (Nostoc) PCC 7120 responds to starvation for nitrogen compounds by differentiating approximately every 10th cell in the filament into nitrogen-fixing cells called heterocysts. Heterocyst formation is subject to complex regulation, which involves an unusual response regulator PatA that contains a CheY-like phosphoacceptor (receiver, REC) domain at its C-terminus. PatA-like response regulators are widespread in cyanobacteria; one of them regulates phototaxis in Synechocystis PCC 6803. Sequence analysis of PatA revealed, in addition to the REC domain, a previously undetected, conserved domain, which we named PATAN (after PatA N-terminus), and a potential helix-turn-helix (HTH) domain. PATAN domains are encoded in a variety of environmental bacteria and archaea, often in several copies per genome, and are typically associated with REC, Roadblock and other signal transduction domains, or with DNA-binding HTH domains. Many PATAN domains contain insertions of a small additional domain, termed a-clip, which is predicted to form a four-helix bundle. PATAN domains appear to participate in protein-protein interactions that regulate gliding motility and processes of cell development and differentiation in cyanobacteria and some proteobacteria, such as Myxococcus xanthus and Geobacter sulfurreducens. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 39 TC 16 Z9 18 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2006 VL 22 IS 11 BP 1297 EP 1301 DI 10.1093/bioinformatics/bt/096 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 054DJ UT WOS:000238356700003 PM 16543275 ER PT J AU Ogurtsov, AY Shabalina, SA Kondrashov, AS Roytberg, MA AF Ogurtsov, AY Shabalina, SA Kondrashov, AS Roytberg, MA TI Analysis of internal loops within the RNA secondary structure in almost quadratic time SO BIOINFORMATICS LA English DT Article ID THERMODYNAMIC PARAMETERS; PREDICTION; ALGORITHM; GENOMES; CELLS; SIRNA AB Motivation: Evaluating all possible internal loops is one of the key steps in predicting the optimal secondary structure of an RNA molecule. The best algorithm available runs in time O(L-3), L is the length of the RNA. Results: We propose a new algorithm for evaluating internal loops, its run-time is O(M*log(2)L), M < L-2 is a number of possible nucleotide pairings. We created a software tool Afold which predicts the optimal secondary structure of RNA molecules of lengths up to 28 000 nt, using a computer with 2 Gb RAM. We also propose algorithms constructing sets of conditionally optimal multi-branch loop free (MLF) structures, e.g. the set that for every possible pairing (x, y) contains an optimal MLF structure in which nucleotides x and y form a pair. All the algorithms have run-time O(M*log(2)L). C1 Russian Acad Sci, Inst Math Problems Biol, Pushchino 142290, Moscow Region, Russia. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Roytberg, MA (reprint author), Russian Acad Sci, Inst Math Problems Biol, Pushchino 142290, Moscow Region, Russia. EM MRoytberg@impb.psn.ru RI Shabalina, Svetlana/N-8939-2013; Roytberg, Mikhail/O-1299-2013 OI Shabalina, Svetlana/0000-0003-2272-7473; Roytberg, Mikhail/0000-0002-5848-367X NR 27 TC 21 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2006 VL 22 IS 11 BP 1317 EP 1324 DI 10.1093/bioinformatics/bt/083 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 054DJ UT WOS:000238356700006 PM 16543280 ER PT J AU Wainreb, G Haspel, N Wolfson, HJ Nussinov, R AF Wainreb, Gilad Haspel, Nurit Wolfson, Haim J. Nussinov, Ruth TI A permissive secondary structure-guided superposition tool for clustering of protein fragments toward protein structure prediction via fragment assembly SO BIOINFORMATICS LA English DT Article ID STRUCTURE ALIGNMENT; SEQUENCE ALIGNMENT; TERTIARY STRUCTURE; FOLDING PATHWAYS; TRANSITION-STATE; ALGORITHM; FUNNELS; OPTIMIZATION; LEVINTHAL; STABILITY AB Motivation: Secondary-Structure Guided Superposition tool (SSGS) is a permissive secondary structure-based algorithm for matching of protein structures and in particular their fragments. The algorithm was developed towards protein structure prediction via fragment assembly. Results: In a fragment-based structural prediction scheme, a protein sequence is cut into building blocks (BBs). The BBs are assembled to predict their relative 3D arrangement. Finally, the assemblies are refined. To implement this prediction scheme, a clustered structural library representing sequence patterns for protein fragments is essential. To create a library, BBs generated by cutting proteins from the PDB are compared and structurally similar BBs are clustered. To allow structural comparison and clustering of the BBs, which are often relatively short with flexible loops, we have devised SSGS. SSGS maintains high similarity between cluster members and is highly efficient. When it comes to comparing BBs for clustering purposes, the algorithm obtains better results than other, non-secondary structure guided protein superimposition algorithms. C1 Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Fac Exact Sci, Sch Comp Sci, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. NCI, SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Nussinov, R (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011; Haspel, Nurit/D-1961-2017 FU NCI NIH HHS [N01-CO-12400] NR 56 TC 4 Z9 4 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 1 PY 2006 VL 22 IS 11 BP 1343 EP 1352 DI 10.1093/bioinformatics/bt/098 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 054DJ UT WOS:000238356700009 PM 16543273 ER PT J AU Grant, P Zheng, Y Pant, HC AF Grant, P Zheng, Y Pant, HC TI Squid (Loligo pealei) giant fiber system: A model for studying neurodegeneration and dementia? SO BIOLOGICAL BULLETIN LA English DT Article ID NEUROFILAMENT AXONAL-TRANSPORT; AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN SUPEROXIDE-DISMUTASE; C-TERMINAL PHOSPHORYLATION; PROTEIN-KINASE; ALZHEIMERS-DISEASE; OCTOPUS-VULGARIS; NF-H; TOPOGRAPHIC REGULATION; STELLATE GANGLION AB In many neurodegenerative disorders that lead to memory loss and dementia, the brain pathology responsible for neuronal loss is marked by accumulations of proteins in the form of extracellular plaques and intracellular filamentous tangles, containing hyperphosphorylated cytoskeletal proteins. These are assumed to arise as a consequence of deregulation of a normal pattern of topographic phosphorylation-that is, an abnormal shift of cytoskeletal protein phosphorylation from the normal axonal compartment to cell bodies. Although decades of studies have been directed to this problem, biochemical approaches in mammalian systems are limited: neurons are too small to permit separation of cell body and axon compartments. Since the pioneering studies of Hodgkin and Huxley on the giant fiber system of the squid, however, the stellate ganglion and its giant axons have been the focus of a large literature on the physiology and biochemistry of neuron function. This review concentrates on a host of studies in our laboratory and others on the factors regulating compartment-specific patterns of cytoskeletal protein phosphorylation (primarily neurofilaments) in an effort to establish a normal baseline of information for further studies on neurodegeneration. On the basis of these data, a model of topographic regulation is proposed that offers several possibilities for further studies on potential sites of deregulation that may lead to pathologies resembling those seen in mammalian and human brains showing neurodegeneration, dementia, and neuronal cell death. C1 NINDS, LNC, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, LNC, NIH, Bldg 49,Rm 2A28, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU Intramural NIH HHS NR 90 TC 14 Z9 14 U1 2 U2 9 PU MARINE BIOLOGICAL LABORATORY PI WOODS HOLE PA 7 MBL ST, WOODS HOLE, MA 02543 USA SN 0006-3185 J9 BIOL BULL-US JI Biol. Bull. PD JUN PY 2006 VL 210 IS 3 BP 318 EP 333 DI 10.2307/4134568 PG 16 WC Biology; Marine & Freshwater Biology SC Life Sciences & Biomedicine - Other Topics; Marine & Freshwater Biology GA 058VQ UT WOS:000238693100015 PM 16801505 ER PT J AU Zarate, CA Singh, J Manji, HK AF Zarate, CA Singh, J Manji, HK TI Cellular plasticity cascades: Targets for the development of novel therapeutics for bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Review DE antidepressant; bipolar disorder; depression; glutamate; plasticity; treatment ID METABOTROPIC GLUTAMATE RECEPTORS; GLYCOGEN-SYNTHASE KINASE-3; ANTIDEPRESSANT ADMINISTRATION INCREASES; EMERGING EXPERIMENTAL THERAPEUTICS; HISTONE DEACETYLASE INHIBITORS; PLACEBO-CONTROLLED TRIAL; LONG-TERM POTENTIATION; OPEN-LABEL TRIAL; IN-VIVO EVIDENCE; MAJOR DEPRESSION AB For a number of patients with bipolar disorder, current pharmacotherapy is generally insufficient. Despite adequate treatment, patients continue to have recurrent mood episodes, residual symptoms, functional impairment, psychosocial disability, and significant medical and psychiatric comorbidity. Drug development for bipolar disorder may occur through one of two approaches: the first is by understanding the therapeutically relevant biochemical targets of currently effective medications. Two promising direct targets of lithium and valproate are glycogen synthase kinase-3 and histone deacetylase. The second path results from our understanding that severe mood disorders, although not classical neurodegenerative disorders, are associated with regional impairments of structural plasticity and cellular resilience. This suggests that effective treatments will need to provide both trophic and neurochemical support, which serves to enhance and maintain normal synaptic connectivity, thereby allowing the chemical signal to reinstate the optimal functioning of critical circuits necessary for normal affective functioning. For many refractory patients, drugs mimicking "traditional" strategies, which directly or indirectly alter monoaminergic levels, may be of limited benefit. Newer "Plasticity enhancing" strategies that may have utility in the treatment of mood disorders include inhibitors of glutamate release, N-methyl-D-aspartate antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid potentiators, cyclic adenosine monopbosphate phosphodiesterase inhibitors, and glucocorticoid receptor antagonists. C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Res Program, 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 FU Intramural NIH HHS NR 151 TC 154 Z9 159 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2006 VL 59 IS 11 BP 1006 EP 1020 DI 10.1016/j.biopsych.2005.10.021 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 054ZB UT WOS:000238416000005 PM 16487491 ER PT J AU Vasa, RA Carlino, AR Pine, DS AF Vasa, Roma A. Carlino, Anthony R. Pine, Daniel S. TI Pharmacotherapy of depressed children and adolescents: Current issues and potential directions SO BIOLOGICAL PSYCHIATRY LA English DT Review DE major depression; pediatric; antidepressants; clinical trials ID PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; PREPUBERTAL MAJOR DEPRESSION; PITUITARY-ADRENAL AXIS; AGE-OF-ONSET; ANXIETY DISORDERS; DOUBLE-BLIND; NEUROENDOCRINE RESPONSE; PERCEPTUAL ASYMMETRY AB The recent deliberations by the U.S. Food and Drug Administration (FDA) regarding the relationship between antidepressants and suicidality in children have incited debates about the safety of these medications for the treatment of pediatric depression. In light of these events, this review discusses four issues pertaining to pharmacotherapy for pediatric depression. First, we summarize pertinent data from randomized controlled trials of antidepressants for pediatric depression. These data provide strong support for fluoxetine and modest support for the other antidepressants. Second, we examine the outcome of the FDA meta-analysis of the data on antidepressant-induced suicidality, with specific emphasis on the methodological limitations of this analysis. Third, we consider the collective implications of the antidepressant efficacy and suicidality data on clinical practice. Specifically, we present several compelling arguments that justify the continued use of antidepressants for pediatric depression, despite the inherent limitations of these medications. Finally, we review several pathophysiological factors that might provide insights into treatment response and impact the design of future pharmacotherapy studies of depression. These factors relate to diagnostic heterogeneity, developmental consistency, and psychobiology. Potentially novel pharmacotherapies are also discussed. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA. NIMH, Bethesda, MD 20892 USA. RP Vasa, RA (reprint author), Kennedy Krieger Res Inst, 3901 Greenspring Ave, Baltimore, MD 21211 USA. EM vasa@kennedykrieger.org NR 87 TC 13 Z9 14 U1 5 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2006 VL 59 IS 11 BP 1021 EP 1028 DI 10.1016/j.biopsych.2005.10.010 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 054ZB UT WOS:000238416000006 PM 16406250 ER PT J AU Lissek, S Pine, DS Grillon, C AF Lissek, S Pine, DS Grillon, C TI The strong situation: A potential impediment to studying the psychobiology and pharmacology of anxiety disorders SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE anxiety disorders; fear-induction; psychophysiology; psychopharmacology; Strong situation ID POSTTRAUMATIC-STRESS-DISORDER; PANIC DISORDER; SOCIAL PHOBIA; AMYGDALA RESPONSE; VIETNAM VETERANS; STARTLE; FEAR; HUMANS; MISINTERPRETATION; INFORMATION AB The strong situation, as formulated by social psychologists, refers to an experimental condition offering unambiguous stimuli predicting or constituting hedonically strong events that uniformly guide response sets across individuals. In relation to fear and anxiety, the strong situation results from the unambiguous threat of an imminent and dangerous stimulus that evokes the adaptive fear response among anxiety patients and healthy controls alike. The current paper describes evidence that weakening the experimental situation through reducing the certainty, temporal proximity, and/or potency of the aversive stimulus may facilitate the emergence of patient-control differences in psychobiological measures of anxious arousal. Additionally, weak situations may be useful for testing the clinical utility of anxiolytic agents, given that pharmacological treatments of anxiety disorders are not intended to reduce the adaptive, normative response likely evoked by strong threat situations. (c) 2005 Elsevier B.V. All rights reserved. C1 NIH, DHHS, NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Lissek, S (reprint author), NIH, DHHS, NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. EM lisseks@intra.nimh.nih.gov RI Lissek, Shmuel/B-6577-2008 FU Intramural NIH HHS NR 42 TC 64 Z9 64 U1 5 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JUN PY 2006 VL 72 IS 3 BP 265 EP 270 DI 10.1016/j.biopsycho.2005.11.004 PG 6 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 043PE UT WOS:000237612700004 PM 16343731 ER PT J AU Altmaier, EM Ewell, M McQuellon, R Geller, N Carter, SL Henslee-Downey, J Davies, S Papadopoulos, E Yanovich, S Gingrich, R AF Altmaier, EM Ewell, M McQuellon, R Geller, N Carter, SL Henslee-Downey, J Davies, S Papadopoulos, E Yanovich, S Gingrich, R TI The effect of unrelated donor marrow transplantation on health-related quality of life: A report of the unrelated donor marrow transplantation trial (T-cell depletion trial) SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE quality of life; bone marrow transplantation; T-cell depletion ID VERSUS-HOST-DISEASE; FUNCTIONAL ASSESSMENT; RECIPIENTS; PROPHYLAXIS; OUTCOMES AB The primary objective of this study was to compare health-related quality of life (HRQL) in adult patients undergoing either ex vivo T cell-depleted bone marrow transplantation or conventional marrow transplantation. Data on patients' HRQL were gathered as part of a multicenter randomized trial comparing the effect of ex vivo T-cell depletion versus methotrexate and cyclosporine immunosuppression on disease-free survival. HRQL assessments were conducted at baseline, day +100, 6 months, 1 year, and 3 years. There were no treatment arm differences 1 year after transplantation on the Functional Assessment of Cancer Therapy, Bone Marrow Transplantation, the Medical Outcomes Study Short-Form 36, and the Centers for Epidemiological Studies of Depression. The lack of treatment differences was robust across types of data analyses that took baseline functioning into account and that recognized the sensitivity of outcome measures to assumptions concerning missing data. The trajectory of recovery revealed an initial decrease in function and then a recovery to pretreatment levels that were similar for both treatment arms. Furthermore, the patients in both treatment groups returned to a functional level that approximated general US population norms. Even though the incidence of acute graft-versus-host disease was slightly higher in the conventional treatment arm, T-cell depletion did not differentially affect HRQL at 1 year after transplantation. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Iowa, Lindquist Ctr 360, Iowa City, IA 52242 USA. EMMES Corp, Rockville, MD USA. Wake Forest Univ, Baptist Med Ctr, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. NHLBI, Bethesda, MD 20892 USA. Univ S Carolina, Div Transplantat Med, Columbia, SC 29208 USA. Univ Minnesota, Minneapolis, MN USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. RP Altmaier, EM (reprint author), Univ Iowa, Lindquist Ctr 360, Iowa City, IA 52242 USA. EM elizabeth-altmaier@uiowa.edu FU NHLBI NIH HHS [N01-HB-47097, N01-HB-47094, N01-HB-47095, N01-HB-47098] NR 25 TC 17 Z9 17 U1 1 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2006 VL 12 IS 6 BP 648 EP 655 DI 10.1016/j.bbmt.2006.01.003 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 051SM UT WOS:000238181100007 PM 16737938 ER PT J AU Griffith, LM Pavletic, SZ Tyndall, A Gratwohl, A Furst, DE Forman, SJ Nash, RA AF Griffith, LM Pavletic, SZ Tyndall, A Gratwohl, A Furst, DE Forman, SJ Nash, RA TI Target populations in allogeneic hematopoietic cell transplantation for autoimmune diseases - A workshop accompanying: Cellular therapy for treatment of autoimmune diseases, basic science and clinical studies, including new developments in hematopoietic and mesenchymal stem cell therapy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Letter ID APLASTIC-ANEMIA C1 NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. Felix Platter Hosp, Dept Rheumatol, Basel, Switzerland. Univ Basel Hosp, Dept Hematol, CH-4031 Basel, Switzerland. Univ Calif Los Angeles, Sch Med, Dept Med, Div Rheumatol, Los Angeles, CA 90024 USA. City Hope Natl Med Ctr, Div Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Div Med Oncol & Therapeut Res, Duarte, CA 91010 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. RP Griffith, LM (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 11 Z9 12 U1 1 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2006 VL 12 IS 6 BP 688 EP 690 DI 10.1016/j.bbmt.2006.02.007 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 051SM UT WOS:000238181100012 PM 16737943 ER PT J AU Grandjean-Laquerrier, A Laquerriere, P Jallot, E Nedelec, JM Guenounou, M Laurent-Maquin, D Phillips, TM AF Grandjean-Laquerrier, A Laquerriere, P Jallot, E Nedelec, JM Guenounou, M Laurent-Maquin, D Phillips, TM TI Influence of the zinc concentration of sol-gel derived zinc substituted hydroxyapatite on cytokine production by human monocytes in vitro SO BIOMATERIALS LA English DT Article DE hydroxyapatite particles; cytokines; inflammation; zinc; monocytes ID NECROSIS-FACTOR-ALPHA; PROTEIN-SYNTHESIS; TISSUE-CULTURE; PARTICLES; BONE; ACTIVATION; OSTEOLYSIS; RELEASE; BIOLOGY; CELLS AB A possible complication associated with the implantation of hydroxyapatite (HA)-based prosthesis is the release of particles. These particles call be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators such as cytokines that cause osteoclasts activation. The present work, describes studies on the effect of sol-gel derived zinc-substituted HA particles with various zinc substitution percentages (0.5-2%) on cytokine production (TNF-alpha, IL-1 beta, IL-6, IL-10, and IL-8) by both LPS-stimulated or unstimulated human monocytes. Our data demonstrates that the zinc has an effect on cytokines production. It decreases the production of TNF-alpha and increases the production of IL-8 by unstimulated cells. Using LPS-stimulated cells, it decreases the production of inflammatory cytokines and increases the production of anti-inflammatory cytokine (IL-10), indicating that zinc-substituted hydroxyapatite has favourable effects on the cytokines production by monocytes. (c) 2006 Elsevier Ltd. All rights reserved. C1 INSERM, ERM 0203, IFR 53, F-51685 Reims 2, France. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. Univ Clermont Ferrand, Lab Phys Corpusculaire Clermont Ferrand, F-63177 Clermont Ferrand, France. Univ Clermont Ferrand, CNRS, UMR 6002, Lab Mat Inorgan, F-63177 Aubiere, France. IPCM, EA 3796, IFR53, F-51100 Reims, France. RP Laquerriere, P (reprint author), INSERM, ERM 0203, IFR 53, 21 Rue Clement Ader,BP 138, F-51685 Reims 2, France. EM patrice.laquerriere@univ-reims.fr RI NEDELEC, jean-marie/A-6920-2008; Laquerriere, Patrice/P-1025-2016 OI NEDELEC, jean-marie/0000-0002-8243-6849; Laquerriere, Patrice/0000-0001-7637-9094 NR 24 TC 49 Z9 53 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 2006 VL 27 IS 17 BP 3195 EP 3200 DI 10.1016/j.biomaterial.2006.01.024 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 029LL UT WOS:000236564000005 PM 16487585 ER PT J AU Phillips, TM Wellner, EF AF Phillips, Terry M. Wellner, Edward F. TI Measurement of naproxen in human plasma by chip-based immunoaffinity capillary electrophoresis SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article DE electrokinetic assay; naproxen; capillary electrophoresis ID SOLID-PHASE MICROEXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; INDUCED FLUORESCENCE DETECTION; MASS-SPECTROMETRY; BODY-FLUIDS; URINE; IBUPROFEN; ONLINE; DRUGS; SERUM AB An electrokinetic immunoassay performed in a chip-based capillary electrophoresis system is described for the rapid measurement of naproxen in human plasma. The system employs a fluorescently labeled antibody to capture and detect the analyte of interest within a 5 min total assay time with an LOD of 0.025 mu g/mL and a saturation level of 450 mu g/mL. The system compared well with a conventional HPLC technique but was found to be much faster. Application of the electrokinetic assay to the study of patients with allergy to naproxen demonstrated increased concentrations of the drug extending past the predicted elimination half-life. The portability of the system and its ability to process up to 18 samples per hour makes it suitable for use in emergency room situations. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NIH, UAIR, DBEPS, Off Res Serv, Bethesda, MD 20892 USA. NIH, Instrument Res & Dev Resources, DBEPS, Off Res Serv, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), NIH, UAIR, DBEPS, Off Res Serv, 13-3N15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM phillipt@mail.nih.gov NR 42 TC 22 Z9 22 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD JUN-JUL PY 2006 VL 20 IS 6-7 BP 662 EP 667 DI 10.1002/bmc.673 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 063VO UT WOS:000239048200021 PM 16779772 ER PT J AU Korn, EL Freidlin, B AF Korn, EL Freidlin, B TI The likelihood as statistical evidence in multiple comparisons in clinical trials: No free lunch SO BIOMETRICAL JOURNAL LA English DT Article DE Bayesian methods; interim monitoring; frequentist methods; subgroup analysis; subset analysis; likelihood ratio ID NULL HYPOTHESIS AB The likelihood ratio summarizes the strength of statistical evidence for one simple pre-determined hypothesis versus another. However, it does not directly address the multiple comparisons problem. In this paper we discuss some concerns related to the application of likelihood ratio methods to several multiple comparisons issues in clinical trials, in particular, subgroup analysis, multiple variables, interim monitoring, and data driven choice of hypotheses. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN 8129, Bethesda, MD 20892 USA. EM korne@ctep.nci.nih.gov NR 41 TC 4 Z9 4 U1 0 U2 7 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD JUN PY 2006 VL 48 IS 3 BP 346 EP 355 DI 10.1002/bimj.200510216 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 059YM UT WOS:000238768100002 PM 16845900 ER PT J AU Cai, B Dunson, DB AF Cai, B Dunson, DB TI Bayesian covariance selection in generalized linear mixed models SO BIOMETRICS LA English DT Article DE Bayes factor; latent variables; marginal likelihood; MCMC algorithm; random effects; stochastic search; Taylor series; variable selection ID HIERARCHICAL-MODELS; VARIABLE SELECTION; LONGITUDINAL DATA; COMPONENT; HOMOGENEITY; INFERENCE; MATRICES; TESTS AB The generalized linear mixed model (GLMM), which extends the generalized linear model (GLM) to incorporate random effects characterizing heterogeneity among subjects, is widely used in analyzing correlated and longitudinal data. Although there is often interest in identifying the subset of predictors that have random effects, random effects selection can be challenging, particularly when outcome distributions are nonnormal. This article proposes a fully Bayesian approach to the problem of simultaneous selection of fixed and random effects in GLMMs. Integrating out the random effects induces a covariance structure on the multivariate outcome data, and an important problem that we also consider is that of covariance selection. Our approach relies on variable selection-type mixture priors for the components in a special Cholesky decomposition of the random effects covariance. A stochastic search MCMC algorithm is developed, which relies on Gibbs sampling, with Taylor series expansions used to approximate intractable integrals. Simulated data examples are presented for different exponential family distributions, and the approach is applied to discrete survival data from a time-to-pregnancy study. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Cai, B (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM cai@niehs.nih.gov NR 43 TC 32 Z9 32 U1 3 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2006 VL 62 IS 2 BP 446 EP 457 DI 10.1111/j.1541-0420.2005.00499.x PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 054NP UT WOS:000238384500013 PM 16918908 ER PT J AU Katki, HA AF Katki, HA TI Effect of misreported family history on Mendelian mutation prediction models SO BIOMETRICS LA English DT Article DE Bayes factor; BRCA1; BRCA2; BRCAPRO; CRCAPRO; family history; genetic counseling; measurement error ID OVARIAN-CANCER; BREAST; BRCA1; RISK AB People with familial history of disease often consult with genetic counselors about their chance of carrying mutations that increase disease risk. To aid them, genetic counselors use Mendelian models that predict whether the person carries deleterious mutations based on their reported family history. Such models rely on accurate reporting of each member's diagnosis and age of diagnosis, but this information may be inaccurate. Commonly encountered errors in family history can significantly distort predictions, and thus can alter the clinical management of people undergoing counseling, screening, or genetic testing. We derive general results about the distortion in the carrier probability estimate caused by misreported diagnoses in relatives. We show that the Bayes factor that channels all family history information has a convenient and intuitive interpretation. We focus on the ratio of the carrier odds given correct diagnosis versus given misreported diagnosis to measure the impact of errors. We derive the general form of this ratio and approximate it in realistic cases. Misreported age of diagnosis usually causes less distortion than misreported diagnosis. This is the first systematic quantitative assessment of the effect of misreported family history on mutation prediction. We apply the results to the BRCAPRO model, which predicts the risk of carrying a mutation in the breast and ovarian cancer genes BRCA1 and BRCA2. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Katki, HA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. EM katkih@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 FU Intramural NIH HHS; NCI NIH HHS [R01 CA105090-02, R01 CA105090-04, R01 CA105090, R01 CA105090-01A1, R01 CA105090-03] NR 10 TC 9 Z9 9 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2006 VL 62 IS 2 BP 478 EP 487 DI 10.1111/j.1541-0420.2005.00488.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 054NP UT WOS:000238384500017 PM 16918912 ER PT J AU Chen, Z Dunson, DB AF Chen, Z Dunson, DB TI Untitled - Reply SO BIOMETRICS LA English DT Letter C1 Univ Penn, Dept Biostat & Epidemiol, Sch Med, Philadelphia, PA 19401 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Chen, Z (reprint author), Univ Penn, Dept Biostat & Epidemiol, Sch Med, Philadelphia, PA 19401 USA. EM dunson1@niehs.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2006 VL 62 IS 2 BP 623 EP 624 DI 10.1111/j.1541-0420.2006.00586_2.x PG 2 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 054NP UT WOS:000238384500034 ER PT J AU Kulkarni, SS Kopajtic, TA Katz, JL Newman, AH AF Kulkarni, SS Kopajtic, TA Katz, JL Newman, AH TI Comparative structure-activity relationships of benztropine analogues at the dopamine transporter and histamine H-1 receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE dopamine transporter; benztropines; histamine H-1 receptor; molecular modeling; cocaine; pharmacophore ID ANTAGONIST-BINDING-SITE; MOLECULAR-FIELD ANALYSIS; UPTAKE INHIBITORS; H-1-RECEPTOR ANTAGONISTS; COCAINE-ABUSE; 3-ALPHA-(DIPHENYLMETHOXY)TROPANE ANALOGS; 3-ALPHA-DIPHENYLMETHOXYTROPANE ANALOGS; MONOAMINE TRANSPORTERS; LIGANDS; PHARMACOTHERAPIES AB Benztropine (BZT) and its analogues inhibit dopamine uptake and bind with moderate to high affinity to the dopamine transporter (DAT). However, many of these Compounds, in contrast to other monoamine uptake inhibitors, lack cocaine-like behavioral effects and fail to potentiate the effects of cocaine. The BZT analogues also exhibit varied binding affinities for muscarinic M-1 and histamine H-1 receptors. In this study, a comparative analysis was conducted of pharmacophoric features with respect to the activities of BZT analogues at the DAT and at the histamine H-1 receptor. The BZT analogues showed a wide range of histamine H-1 receptor (K-i = 16-37,600 nM) and DAT (Ki = 8.5-6370 nM) binding affinities. A stereoselective histamine H-1-antagonist pharmacophore, using a five-point superimposition of classical antagonists on the template, cyproheptadine, was developed. A series of superimpositions and comparisons were performed with various analogues of BZT. In general, smaller substituents were well tolerated oil the aromatic rings of the diphenyl methoxy group for both the DAT and H-1 receptor, however, for the H-1 receptor, substitution at only one of the aromatic rings was preferred. The substituents at the 2- and N-positions of the tropane ring were preferred for DAT, however, these groups seem to overlap receptor essential regions in the histamine H-1 receptor. Molecular models at the DAT and the histamine H-1 receptor provide further insight into the structural requirements for binding affinity and selectivity that can be implemented in future drug design. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 5500,Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 FU Intramural NIH HHS [Z99 DA999999] NR 38 TC 6 Z9 6 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2006 VL 14 IS 11 BP 3625 EP 3634 DI 10.1016/j.bmc.2006.01.017 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 042AE UT WOS:000237498500001 PM 16460947 ER PT J AU Donohue, SR Halldin, C Pike, VW AF Donohue, SR Halldin, C Pike, VW TI Synthesis and structure-activity relationships (SARs) of 1,5-diarylpyrazole cannabinoid type-1 (CB1) receptor ligands for potential use in molecular imaging SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE CB1 receptor; PET; 1,5-diarylpyrazoles; carbon-11; NIDA 41087; rimonabant ID IN-VIVO; BRAIN; RADIOLIGANDS; ANTAGONIST; BINDING; LOCALIZATION; RECOGNITION; ACTIVATION; EXPRESSION; SR141716 AB Cannabinoid type-l (CB1) receptor ligands, derived from the 1,5-diarylpyrazole core template of rimonabant (Acomplia (R)), have been the focus of several studies aimed at examining structure-activity relationships (SARs). The purpose of this study was to design and synthesize a set of compounds based on the 1,5-diarylpyrazole template while focusing on the potential for discovery of CB1 receptor radioligands that might be used as probes with in vivo molecular imaging. Each synthesized ligand was evaluated for potency as an antagonist at CB1 and cannabinoid type-2 (CB2) receptors in vitro using a GTP gamma S-35-binding assay. c log P values were calculated with Pallas 3.0. The antagonist binding affinities (K-B) at CB1 receptors ranged from I I to > 16,000 nM, CB1 versus CB2 selectivities from 0.6 to 773, and c log Ps from 3.61 to 6.25. An interesting new ligand, namely N-(piperidin-1-yl)-1-(2-bromophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazole-3-carboxamide (9j), emerged from the synthesized set with appealing properties (K-B = 11 nM; CB1 selectivity > 773; c log P = 5.85), for labeling with carbon-11 and development as a radioligand for imaging brain CB1 receptors in vivo with positron emission tomography (PET). (c) 2006 Elsevier Ltd. All rights reserved. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. RP Donohue, SR (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM donohues@intra.nimh.nih.gov FU Intramural NIH HHS NR 32 TC 28 Z9 28 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2006 VL 14 IS 11 BP 3712 EP 3720 DI 10.1016/j.bmc.2006.01.047 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 042AE UT WOS:000237498500010 PM 16466922 ER PT J AU Lang, LX Jagoda, E Ma, Y Sassaman, MB Eckelman, WC AF Lang, LX Jagoda, E Ma, Y Sassaman, MB Eckelman, WC TI Synthesis and in vivo biodistribution of F-18 labeled 3-cis-, 3-trans-, 4-cis-, and 4-trans-fluorocyclohexane derivatives of WAY 100635 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 5-HT1A receptors; fluorine-18; WAY 100635; in vitro metabolites ID 5-HT1A RECEPTOR ANTAGONIST; POSTSYNAPTIC 5-HT(1A) RECEPTORS; SELECTIVE ANTAGONIST; RAT-BRAIN; P-MPPI; PET; BINDING; ANALOGS; CHROMATOGRAPHY; RADIOLIGANDS AB Radioligands that are specific for the serotonin 5-HT1A receptor will be useful in characterizing the physiological action of this receptor subtype. With radioligands of varying pharmacokinetic properties, investigators can measure not only receptor density, but also the effect of endogenous serotonin concentration. To this end, three additional fluorinated analogs of WAY 100635 were prepared and evaluated as 5-HT1A receptor ligands of varyin vertical bar%1e[OK]g pharmacokinetic properties based on our previous studies. These four compounds are cis-4-fluoro-, trans-4-fluoro-, cis-3-fluoro-, and trans-3-fluoro-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-(pyridin-2-yl)cyclohexanecarboxamides (FCWAYs). All four compounds were characterized and radiolabeled with fluorine-18, a 109.7 min half-life radionuclide used in positron emission tomography. We then determined in vitro inhibition constants at the 5-HT1A receptor; in vitro metabolic profile, using rat hepatocytes and liquid chromatography/mass spectroscopy (LC/MS); and the rate of defluorination and hippocampus to cerebellum ratio ex vivo. This led to the conclusion that high affinity 4-trans-F-18 FCWAY had the best properties for measuring receptor density given its high hippocampus to cerebellum ratio and 3-cis-F-18 FCWAY had the best properties for measuring dynamic change in receptors, with lower affinity and faster pharmacokinetics. (c) 2006 Elsevier Ltd. All rights reserved. C1 Warren Grant Magnuson Clin Ctr, PET Dept, NIH, Bethesda, MD 20814 USA. RP Lang, LX (reprint author), Warren Grant Magnuson Clin Ctr, PET Dept, NIH, Bethesda, MD 20814 USA. EM llang@mail.cc.nih.gov NR 25 TC 20 Z9 20 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2006 VL 14 IS 11 BP 3737 EP 3748 DI 10.1016/j.bmc.2006.01.064 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 042AE UT WOS:000237498500012 PM 16488611 ER PT J AU Deng, JX Kelley, JA Barchi, JJ Sanchez, T Dayam, R Pommier, Y Neamati, N AF Deng, JX Kelley, JA Barchi, JJ Sanchez, T Dayam, R Pommier, Y Neamati, N TI Mining the NCI antiviral compounds for HIV-1 integrase inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV integrase inhibitor; drug design; NCI database; docking; antiviral activity ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; STRAND TRANSFER; 3D DATABASE; CORE DOMAIN; DESIGN; RESISTANCE; DRUGS; IDENTIFICATION; PROTEIN AB HIV-1 integrase (IN) is an essential enzyme for effective viral replication and is it validated target for the development of antiretroviral drugs. Currently, there are no approved drugs targeting this enzyme. In this study, we have identified I I structurally diverse small-molecule inhibitors of IN. These compounds have been selected by mining the moderately active antiviral molecules from a collection of 90,000 compounds screened by the National Cancer Institute (NCI) Antiviral Program. These compounds, which were screened at the NCI during the past 20 years, resulted in approximately 4000 compounds labeled as 'moderately active.' In our study, chalcone I I shows the most potent activity with an IC50 of 2 +/- 1 mu M against purified IN in the presence of both Mn2+ and Mg2+ as cofactors. Docking simulations using the I I identified inhibitors as a training set have elucidated two unique binding areas within the active site: The first encompasses the conserved D64-D116-E152 motif, while the other involves the flexible loop region formed by amino acid residues 140-149. The tested inhibitors exhibit favorable interactions with important amino acid residues through van der Waals and H-bonding contacts. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. NCI, Canc Res Ctr, Med Chem Lab, Ft Detrick, MD 21702 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM Neamati@usc.edu RI Barchi Jr., Joseph/N-3784-2014 NR 50 TC 22 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2006 VL 14 IS 11 BP 3785 EP 3792 DI 10.1016/j.bmc.2006.01.040 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 042AE UT WOS:000237498500017 PM 16460953 ER PT J AU Boos, TL Greiner, E Calhoun, WJ Prisinzano, TE Nightingale, B Dersch, CM Rothman, RB Jacobson, AE Rice, KC AF Boos, TL Greiner, E Calhoun, WJ Prisinzano, TE Nightingale, B Dersch, CM Rothman, RB Jacobson, AE Rice, KC TI Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl) piperidine, an allosteric modulator of the serotonin transporter SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE N-benzyl GBR analogue synthesis; SAR; allosteric inhibitor; DAT; SERT; NET transporters; cocaine treatment agent ID DOPAMINE TRANSPORTER; HIGH-AFFINITY; COCAINE; ANALOGS; GBR-12909; NOREPINEPHRINE; STIMULANTS; INHIBITORS; REWARD AB A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl) piperidines with substituents at the ortho and meta positions in the aromatic ring of the N-benzyl side chain were synthesized and their affinities and selectivities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined. One analogue, 4-(2(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine (the C-2-trifluoromethyl substituted compound), has been found to act as an allosteric modulator of hSERT binding and function. It had little affinity for any of the transporters. Several compounds showed affinity for the DAT in the low nanomolar range and displayed a broad range of SERT/DAT selectivity ratios and very little affinity for the NET. The pharmacological tools provided by the availability of compounds with varying transporter affinity and selectivity could be used to obtain additional information about the properties a compound should have to act as a useful pharmacotherapeutic tic agent for cocaine addiction and help unravel the pharmacological mechanisms relevant to stimulant abuse. Published by Elsevier Ltd. C1 NIDDKD, Lab Med Chem, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Natl Inst Drug Abuse, Addict Res Ctr, Clin Psychopharmacol Sect, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDKD, Lab Med Chem, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM kr21f@nih.gov RI Prisinzano, Thomas/B-7877-2010 FU Intramural NIH HHS NR 18 TC 15 Z9 15 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2006 VL 14 IS 11 BP 3967 EP 3973 DI 10.1016/j.bmc.2006.01.065 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 042AE UT WOS:000237498500036 PM 16563775 ER PT J AU Krajewski, K Zhang, YJ Parrish, D Deschamps, J Roller, PP Pathak, VK AF Krajewski, K Zhang, YJ Parrish, D Deschamps, J Roller, PP Pathak, VK TI New HIV-1 reverse transcriptase inhibitors based on a tricyclic benzothiophene scaffold: Synthesis, resolution, and inhibitory activity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE reverse transcriptase inhibitors; synthesis; chiral separation; CD spectra; X-ray structures; RT inhibitory assay ID IMMUNODEFICIENCY-VIRUS TYPE-1; NONNUCLEOSIDE INHIBITORS AB We synthesized, separated into enantiomers, and tested for the HIV-1 reverse transcriptase inhibitory activity a group Of analogs of dimethyl-1-(1-piperidynyl)cyclobuta[b][1]benzothiophene-2,2a(7bH)-dicarboxylate (NSC-380292). Absolute configurations of the enantiomers were determined based on absolute X-ray structures and analysis of CD spectra. Within pairs of enantiomers the (R,R)-enantiomer was always much more potent HIV-1 reverse transcriptase inhibitor. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. USN, Res Lab, Washington, DC 20375 USA. RP Roller, PP (reprint author), NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. EM proll@helix.nih.gov; vpathak@ncifcrf.gov OI Deschamps, Jeffrey/0000-0001-5845-0010 FU Intramural NIH HHS NR 12 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JUN 1 PY 2006 VL 16 IS 11 BP 3034 EP 3038 DI 10.1016/j.bmcl.2006.02.049 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 040VC UT WOS:000237407800044 PM 16527484 ER PT J AU Zheng, WJ Brooks, BR AF Zheng, WJ Brooks, BR TI Modeling protein conformational changes by iterative fitting of distance constraints using reoriented normal modes SO BIOPHYSICAL JOURNAL LA English DT Article ID ELASTIC-NETWORK MODEL; MOLECULAR-DYNAMICS SIMULATIONS; MOTIONS; RESTRAINTS AB Recently we have developed a normal-modes-based algorithm that predicts the direction of protein conformational changes given the initial state crystal structure together with a small number of pairwise distance constraints for the end state. Here we significantly extend this method to accurately model both the direction and amplitude of protein conformational changes. The new protocol implements a multisteps search in the conformational space that is driven by iteratively minimizing the error of fitting the given distance constraints and simultaneously enforcing the restraint of low elastic energy. At each step, an incremental structural displacement is computed as a linear combination of the lowest 10 normal modes derived from an elastic network model, whose eigenvectors are reorientated to correct for the distortions caused by the structural displacements in the previous steps. We test this method on a list of 16 pairs of protein structures for which relatively large conformational changes are observed ( root mean square deviation > 3 angstrom), using up to 10 pairwise distance constraints selected by a fluctuation analysis of the initial state structures. This method has achieved a near-optimal performance in almost all cases, and in many cases the final structural models lie within root mean square deviation of 1 similar to 2 angstrom from the native end state structures. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zheng, WJ (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM zhengwj@helix.nih.gov OI Zheng, Wenjun/0000-0002-6236-9765 FU Intramural NIH HHS NR 15 TC 33 Z9 33 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2006 VL 90 IS 12 BP 4327 EP 4336 DI 10.1529/biophysj.105.076836 PG 10 WC Biophysics SC Biophysics GA 048EX UT WOS:000237931500006 PM 16565046 ER PT J AU Veatch, SL Gawrisch, K Keller, SL AF Veatch, SL Gawrisch, K Keller, SL TI Closed-loop miscibility gap and quantitative tie-lines in ternary membranes containing diphytanoyl PC SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE CORRELATION SPECTROSCOPY; GIANT UNILAMELLAR VESICLES; PHOSPHOLIPID MIXTURES; MAGNETIC-RESONANCE; PHASE-SEPARATION; MODEL MEMBRANES; ENERGY-TRANSFER; LIPID-BILAYERS; LIQUID-PHASES; CHOLESTEROL AB Vesicles containing ternary mixtures of diphytanoylphosphatidylcholine, dipalmitoylphosphatidylcholine (DPPC), and cholesterol produce coexisting liquid phases over an unusually large range of temperature and composition. Liquid domains persist well above the DPPC chain melting temperature (41 degrees C), resulting in a closed-loop miscibility gap bounded by two critical points at fixed temperature. Quantitative tie-lines are determined directly from H-2 NMR spectra using a novel analysis, and are found to connect a liquid-disordered phase rich in diphytanoyl PC with a liquid-ordered phase rich in DPPC. The direction of the tie-lines implies that binary DPPC/cholesterol mixtures are in one uniform phase above 41 degrees C. All H-2 NMR results for tie-lines are verified by independent fluorescence microscopy results. C1 Univ Washington, Dept Chem, Seattle, WA 98195 USA. Univ Washington, Dept Phys, Seattle, WA 98195 USA. NIAAA, NIH, Bethesda, MD USA. RP Keller, SL (reprint author), Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada. EM slkeller@chem.washington.edu RI Veatch, Sarah/G-9512-2016 OI Veatch, Sarah/0000-0002-9317-2308 FU Intramural NIH HHS NR 31 TC 116 Z9 118 U1 0 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2006 VL 90 IS 12 BP 4428 EP 4436 DI 10.1529/biophysj.105.080283 PG 9 WC Biophysics SC Biophysics GA 048EX UT WOS:000237931500014 PM 16565062 ER PT J AU Paravastu, AK Petkova, AT Tycko, R AF Paravastu, Anant K. Petkova, Aneta T. Tycko, Robert TI Polymorphic fibril formation by residues 10-40 of the Alzheimer's beta-amyloid peptide SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; ANGLE-SPINNING NMR; SECONDARY-STRUCTURE; PRION PROTEIN; STRUCTURAL FEATURES; ANTIPARALLEL; PARALLEL; ORGANIZATION; FIBRILLOGENESIS AB We report investigations of the morphology and molecular structure of amyloid fibrils comprised of residues 10-40 of the Alzheimer's beta-amyloid peptide (A beta(10-40)), prepared under various solution conditions and degrees of agitation. Omission of residues 1-9 from the full-length Alzheimer's b-amyloid peptide (A beta(1-40)) did not prevent the peptide from forming amyloid fibrils or eliminate fibril polymorphism. These results are consistent with residues 1-9 being disordered in A beta(1-40) fibrils, and show that fibril polymorphism is not a consequence of disorder in residues 1-9. Fibril morphology was analyzed by atomic force and electron microscopy, and secondary structure and inter-side-chain proximity were probed using solid-state NMR. A beta(1-40) fibrils were found to be structurally compatible with A beta(10-40): A beta(1-40) fibril fragments were used to seed the growth of A beta(10-40) fibrils, with propagation of fibril morphology and molecular structure. In addition, comparison of lyophilized and hydrated fibril samples revealed no effect of hydration on molecular structure, indicating that A beta(10-40) fibrils are unlikely to contain bulk water. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS NR 45 TC 132 Z9 133 U1 0 U2 20 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2006 VL 90 IS 12 BP 4618 EP 4629 DI 10.1529/biophysj.105.076927 PG 12 WC Biophysics SC Biophysics GA 048EX UT WOS:000237931500031 PM 16565054 ER PT J AU Brown, PH Schuck, P AF Brown, PH Schuck, P TI Macromolecular size-and-shape distributions by sedimentation velocity analytical ultracentrifugation SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; LAMM EQUATION; COEFFICIENT DISTRIBUTIONS; CONCENTRATION PROFILES; INTEGRAL-EQUATIONS; SOLUTES; SYSTEMS; MODEL; C(S) AB Sedimentation velocity analytical ultracentrifugation is an important tool in the characterization of macromolecules and nanoparticles in solution. The sedimentation coefficient distribution c(s) of Lamm equation solutions is based on the approximation of a single, weight-average frictional coefficient of all particles, determined from the experimental data, which scales the diffusion coefficient to the sedimentation coefficient consistent with the traditional s similar to M-2/3 power law. It provides a high hydrodynamic resolution, where diffusional broadening of the sedimentation boundaries is deconvoluted from the sedimentation coefficient distribution. The approximation of a single weight-average frictional ratio is favored by several experimental factors, and usually gives good results for chemically not too dissimilar macromolecules, such as mixtures of folded proteins. In this communication, we examine an extension to a two-dimensional distribution of sedimentation coefficient and frictional ratio, c( s, f(r)), which is representative of a more general set of size-and-shape distributions, including mass-Stokes radius distributions, c(M, R-S), and sedimentation coefficient-molar mass distributions c(s, M). We show that this can be used to determine average molar masses of macromolecules and characterize macromolecular distributions, without the approximation of any scaling relationship between hydrodynamic and thermodynamic parameters. C1 NIH, Prot Biophys REsource, Div Bioengn & Phys Sci, ORS,Off Director, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, Prot Biophys REsource, Div Bioengn & Phys Sci, ORS,Off Director, Bldg 13,Rm 3N17,13 S Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU NIH HHS [Z01 OD010485-08] NR 41 TC 266 Z9 269 U1 2 U2 41 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2006 VL 90 IS 12 BP 4651 EP 4661 DI 10.1529/biophysj.106.081372 PG 11 WC Biophysics SC Biophysics GA 048EX UT WOS:000237931500035 PM 16565040 ER PT J AU Conrads, TP Hood, BL Veenstra, TD AF Conrads, TP Hood, BL Veenstra, TD TI Sampling and analytical strategies for biomarker discovery using mass spectrometry SO BIOTECHNIQUES LA English DT Review ID 2-DIMENSIONAL ELECTROPHORESIS GELS; PROTEOMIC ANALYSIS; EMBEDDED TISSUES; URINARY PROTEOME; SERUM PROTEOME; HUMAN PLASMA; PROTEINS; IDENTIFICATION; DISPLAY; SPOTS AB There is an often unspoken truth behind the course of scientific investigation that involves not what is necessarily academically worthy of study but rather what is scientifically worthy in the eyes of funding agencies. The perception of worthy research is, as cost is driven in the simplest sense in economics, often driven by demand. Presently, the demand for novel diagnostic and therapeutic protein biomarkers that possess high sensitivity and specificity is placing major impact on the field of proteomics. The focal discovery technology that is being relied on is mass spectrometry (MS), whereas the challenge of biomarker discovery, often lies not in the application of MS but in the underlying proteome sampling and bioinformatic processing strategies. Although biomarker discovery research has been historically technology-driven, it is clear from the meager success in generating validated biomarkers that increasing attention must be placed at the pre-analytic stage, such as sample retrieval and preparation. As diseases vary, so do the combinations of sampling and sample analyses necessary to discover novel biomarkers. In this review, we highlight different strategies used toward biomarker discovery and discuss them in terms of their reliance on technology and methodology. C1 NCI, SAIC Frederick Inc, Lab Prot & Analyt Technol, Ft Detrick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Lab Prot & Analyt Technol, POB B, Ft Detrick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 23 TC 16 Z9 17 U1 0 U2 3 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 2006 VL 40 IS 6 BP 799 EP 805 DI 10.2144/000112196 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 051RR UT WOS:000238178900023 PM 16774124 ER PT J AU Jahnke, GD Price, CJ Marr, MC Myers, CB George, JD AF Jahnke, GD Price, CJ Marr, MC Myers, CB George, JD TI Developmental toxicity evaluation of berberine in rats and mice SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE berberine; development; birth defects; rats; mice; pregnancy; herbal remedy ID ESCHERICHIA-COLI; ANESTHESIA; SULFATE AB BACKGROUND: Berberine, a plant alkaloid, is found in some herbal teas and health-related products. It is a component of goldenseal, an herbal supplement. Berberine chloride dihydrate (BCD) was evaluated for developmental toxicity in rats and mice. METHODS: Berberine chloride dihydrate was administered in the feed to timed-mated Sprague-Dawley (CD) rats (0, 3625, 7250, or 14,500 ppm; on gestational days [GD] 6-20), and Swiss Albino (CD-1) mice (0, 3500, 5250, or 7000 ppm; on GD 6-17). Ingested doses were 0, 282, 531, and 1313 mg/kg/day (rats) and 0, 569, 841, and 1155 mg/kg/day (mice). RESULTS: There were no maternal deaths. The rat maternal lowest observed adverse effect level (LOAEL), based on reduced maternal weight gain, was 7250 ppm. The rat developmental toxicity LOAEL, based on reduced fetal body weight per litter, was 14,500 ppm. In the mouse study, equivocal maternal and developmental toxicity LOAELs were 5250 ppm. Due to scattering of feed in the high dose groups, a gavage study at 1000 mg/kg/day was conducted in both species. CONCLUSIONS: In rats, maternal, but not fetal adverse effects were noted. The maternal toxicity LOAEL remained at 7250 ppm (531 mg/kg/day) based on the feed Study and the developmental toxicity NOAEL was raised to 1000 mg/kg/day BCD based on the gavage study. In the mouse, 33% of the treated females died. Surviving animals had increased relative water intake, and average fetal body weight per litter decreased 5-6% with no change in live litter size. The maternal toxicity LOAEL remained at 5250 ppm (841 mg/kg/day) BCD, based on increased water consumption. The developmental toxicity LOAEL was raised to 1000 mg/kg/day BCD based on decreased fetal body weight. C1 Sci Int Inc, Res Triangle Pk, NC USA. RTI Int, Res Triangle Pk, NC USA. RP Jahnke, GD (reprint author), Natl Inst Environm Hlth Sci, EC 32,POB 12233,Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Jahnke@niehs.nih.gov FU NIEHS NIH HHS [N01-ES-65405] NR 60 TC 21 Z9 25 U1 1 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2006 VL 77 IS 3 BP 195 EP 206 DI 10.1002/bdrb.20075 PG 12 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 059YJ UT WOS:000238767800001 PM 16634078 ER PT J AU Zernecke, A Liehn, EA Gao, JL Kuziel, WA Murphy, PM Weber, C AF Zernecke, A Liehn, EA Gao, JL Kuziel, WA Murphy, PM Weber, C TI Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10 SO BLOOD LA English DT Article ID CORONARY-ARTERY-DISEASE; CHEMOKINE RECEPTOR 5; MATRIX METALLOPROTEINASES; VASCULAR-DISEASE; KNOCKOUT MICE; RANTES; ATHEROGENESIS; RECRUITMENT; EXPRESSION; INTERLEUKIN-10 AB The chemokine RANTES has been implicated in neointimal hyperplasia after arterial injury. We analyzed the differential role of the RANTES receptors CCR1 and CCR5 by genetic deletion in apolipoprotein E-deficient mice. Deficiency in CCR5 significantly reduced neointimal area after arterial wire injury, associated with a decrease in macrophages, CD3(+) T lymphocytes, and CCR2(+) cells. In contrast, CCR1 deficiency did not affect neointimal area or cell content. Deletion of CCR5 entailed an up-regulation of the anti-inflammatory cytokine interleukin 10 (IL-10) in neointimal smooth muscle cells, and its antibody blockade reversed effects in CCR5(-/-) mice. Conversely, proinflammatory interferon gamma was increased in the neointima of CCR1(-/-) mice, and its blockade unmasked a reduction in macrophage recruitment. Our data indicate that CCR5 is more crucial than CCR1 for neointimal plaque formation, and that its attenuation in CCR5(-/-) mice is due to an atheroprotective immune response involving IL-10. This harbors important implications for targeting chemokine receptors in vascular remodeling. C1 Rhein Westfal TH Aachen, Inst Mol Cardiovasc Res, D-5100 Aachen, Germany. Rhein Westfal TH Aachen, Dept Cardiol, D-5100 Aachen, Germany. NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA. Prot Design Labs, Fremont, CA USA. RP Weber, C (reprint author), Univ Klinikum Aachen, Pauwelsstr 30, D-52074 Aachen, Germany. EM cweber@ukaachen.de RI Liehn, Elisa/D-9623-2011; OI Weber, Christian/0000-0003-4610-8714 NR 25 TC 85 Z9 90 U1 0 U2 1 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 JUN 1 PY 2006 VL 107 IS 11 BP 4240 EP 4243 DI 10.1182/blood-2005-09-3922 PG 4 WC Hematology SC Hematology GA 047KD UT WOS:000237877300015 PM 16467202 ER PT J AU Suh, HC Gooya, J Renn, K Friedman, AD Johnson, PF Keller, JR AF Suh, HC Gooya, J Renn, K Friedman, AD Johnson, PF Keller, JR TI C/EBP alpha determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; BINDING-PROTEIN-ALPHA; MURINE ERYTHROLEUKEMIA-CELLS; ERYTHROPOIETIN RECEPTOR GENE; TRANSCRIPTION FACTOR; MACROPHAGE DEVELOPMENT; B-LYMPHOCYTE; PU.1 SPI-1; IN-VITRO; BCR-ABL AB C/EBP alpha is an essential transcription factor required for myeloid differentiation. While C/EBP alpha can act as a cell fate switch to promote granulocyte differentiation in bipotential granulocyte-macrophage progenitors (GMPs), its role in regulating cell fate decisions in more primitive progenitors is not known. We found increased numbers of erythroid progenitors and erythroid cells in C/EBP alpha(-/-) fetal liver (FL). Also, enforced expression of C/EBP alpha in hematopoietic stem cells resulted in a loss of erythroid progenitors and an increase in myeloid cells by inhibition of erythroid development and inducing myeloid differentiation. Conditional expression of C/EBPa in murine erythroleukemia (MEL) cells induced myeloid-specific genes, while inhibiting erythroid-specific gene expression including erythropoietin receptor (EpoR), which suggests a novel mechanism to determine hematopoietic cell fate. Thus, C/EBP alpha functions in hematopoietic cell fate decisions by the dual actions of inhibiting erythroid and inducing myeloid gene expression in multipotential progenitors. C1 SAIC Frederick, Natl Canc Inst, Basic Res Program, Canc Res Ctr, Frederick, MD 20702 USA. Johns Hopkins Univ, Div Pediat Oncol, Baltimore, MD USA. NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, Frederick, MD 21701 USA. RP Keller, JR (reprint author), SAIC Frederick, Natl Canc Inst, Basic Res Program, Canc Res Ctr, Bldg 560,Rm 12-03, Frederick, MD 20702 USA. EM kellerj@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NCI NIH HHS [N01-CO-12400] NR 53 TC 41 Z9 46 U1 0 U2 0 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 JUN 1 PY 2006 VL 107 IS 11 BP 4308 EP 4316 DI 10.1182/blood-2005-06-2216 PG 9 WC Hematology SC Hematology GA 047KD UT WOS:000237877300024 PM 16469877 ER PT J AU Manigold, T Shin, EC Mizukoshi, E Mihalik, K Murthy, KK Rice, CM Piccirillo, CA Rehermann, B AF Manigold, T Shin, EC Mizukoshi, E Mihalik, K Murthy, KK Rice, CM Piccirillo, CA Rehermann, B TI Foxp3(+)CD4(+)CD25(+) T cells control virus-specific memory T cells in chimpanzees that recovered from hepatitis C SO BLOOD LA English DT Article ID CELLULAR IMMUNE-RESPONSES; IN-VITRO PROLIFERATION; REGULATORY CELLS; VIRAL CLEARANCE; INFECTION; ACTIVATION; ANTIGEN; CD4(+); PERSISTENCE; LYMPHOCYTES AB Hepatitis C virus (HCV) poses a global health problem because it readily establishes persistent infection and a vaccine is not available. CD4(+)CD25(+) T cells have been implicated in HCV persistence because their frequency is increased in the blood of HCV-infected patients and their in vitro depletion results in increased IFN-gamma production by HCV-specific T cells. Studying a well-characterized cohort of 16 chimpanzees, the sole animal model for HCV infection, we here demonstrate that the frequency of Foxp3(+)CD4(+)CD25(+) regulatory T cells (T-Regs) and the extent of suppression was as high in spontaneously HCV-recovered chimpanzees as in persistently HCV-Infected chimpanzees. Foxp3(+)CD4(+)CD25(+) T-Regs, suppressed IFN-gamma production, expansion, and activation-induced cell death of HCV-specific T cells after recovery from HCV infection and in persistent HCV infection. Thus, T-Reg cells control HCV-specific T cells not only in persistent infection but also after recovery, where they may regulate memory T-cell responses by controlling their activation and preventing apoptosis. However, Foxp3+CD4+CD25+ TReg cells of both HCV-recovered and HCV-infected chimpanzees differed from Foxp3(+)CD4(+)CD25(+)TReg cells of HCV-naive chimpanzees in increased IL-2 responsiveness and lower T-cell receptor excision circle content, implying a history of in vivo proliferation. This result suggests that HCV infection alters the population of Foxp3+CD4+CD25+ TReg cells. C1 NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 20014 USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78284 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NIH, Immunol Lab, Bethesda, MD USA. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. EM rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883] NR 55 TC 84 Z9 91 U1 0 U2 1 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 JUN 1 PY 2006 VL 107 IS 11 BP 4424 EP 4432 DI 10.1182/blood-2005-09-3903 PG 9 WC Hematology SC Hematology GA 047KD UT WOS:000237877300038 PM 16478885 ER PT J AU Mohan, J Dement-Brown, J Maier, S Ise, T Kempkes, B Tolnay, M AF Mohan, J Dement-Brown, J Maier, S Ise, T Kempkes, B Tolnay, M TI Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1 SO BLOOD LA English DT Article ID HAIRY-CELL LEUKEMIA; FC-RECEPTOR HOMOLOGS; LATENT MEMBRANE-PROTEIN; SIGNAL-BINDING-PROTEIN; MEMORY B-CELLS; J-KAPPA; BURKITTS-LYMPHOMA; GENE-EXPRESSION; UP-REGULATION; IN-VIVO AB Fc-receptor homolog 5 (FcRH5) is a recently identified B-cell membrane protein of unknown function. In Burkitt lymphoma cell lines with chromosome 1q21 abnormalities, FcRH5 expression is deregulated, implicating FcRH5 in lymphomagenesis. Epstein-Barr virus infects and immortalizes B cells, and is implicated in the etiology of several tumors of B-cell origin. Overexpression of genes located on 1q21-25 has been proposed as a surrogate for Epstein-Barr virus in Burkitt lymphoma. We now report that Epstein-Barr virus nuclear antigen 2 (EBNA2) markedly induces the expression of the FcRH5 gene, encoded on chromosome 1q21. Induction occurred in the absence of other viral proteins and did not require de novo protein synthesis. EBNA2 lacks a DNA-binding domain and can target responsive genes through the host DNA binding protein CBF1. We show that induction of FcRH5 by EBNA2 is strictly CBF1 dependent, as it was abolished in CBF1-deficient cells. Accordingly, EBNA2 targeted CBF1 binding sites present in the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation. These results identify FcRH5 as a novel, direct target of EBNA2 that may contribute to the development of Epstein-Barr virus-associated tumors. C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. Natl Res Ctr Environm & Hlth, Inst Clin Mol Biol, Munich, Germany. NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tolnay, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, HFD-123,5600 Fishers Lane, Rockville, MD 20857 USA. EM mate.tolnay@fda.hhs.gov RI Kempkes, Bettina/B-3322-2013 NR 59 TC 15 Z9 16 U1 0 U2 0 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 JUN 1 PY 2006 VL 107 IS 11 BP 4433 EP 4439 DI 10.1182/blood-2005-09-3815 PG 7 WC Hematology SC Hematology GA 047KD UT WOS:000237877300039 PM 16439682 ER PT J AU Akintoye, SO Lam, T Shi, ST Brahim, J Collins, MT Robey, PG AF Akintoye, SO Lam, T Shi, ST Brahim, J Collins, MT Robey, PG TI Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals SO BONE LA English DT Article DE bone marrow stromal cells; orofacial; site-specific; life span; regeneration ID PULP STEM-CELLS; DENTAL-PULP; IN-VIVO; OSTEOBLAST DIFFERENTIATION; ALKALINE-PHOSPHATASE; FIBROUS DYSPLASIA; TRABECULAR BONE; BINDING; GROWTH; AGE AB Autologous grafts from axial and appendicular bones commonly used to repair orofacial bone defects often result in unfavorable outcome. This clinical observation, along with the fact that many bone abnormalities are limited to craniofacial bones, suggests that there are significant differences in bone metabolism in orofacial, axial and appendicular bones. It is plausible that these differences are dictated by site-specificity of embryological progenitor cells and osteogenic properties of resident multipotent human bone marrow stromal cells (hBMSCs). This study investigated skeletal site-specific phenotypic and functional differences between orofacial (maxilla and mandible) and axial (iliac crest) hBMSCs in vitro and in vivo. Primary cultures of maxilla, mandible and iliac crest hBMSCs were established with and without osteogenic inducers. Site-specific characterization included colony forming efficiency, cell proliferation, life span before senescence, relative presence of surface markers, adipogenesis, osteogenesis and transplantation in immunocompromised mice to compare bone regenerative capacity. Compared with iliac crest cells, orofacial hBMSCs (OF-MSCs) proliferated more rapidly with delayed senescence, expressed higher levels of alkaline phosphatase and demonstrated more calcium accumulation in vitro. Cells isolated from the three skeletal sites were variably positive for STRO 1, a marker of hBMSCs. OF-MSCs formed more bone in vivo, while iliac crest hBMSCs formed more compacted bone that included hematopoietic tissue and were more responsive in vitro and in vivo to osteogenic and adipogenic inductions. These data demonstrate that hBMSCs from the same individuals differ in vitro and in vivo in a skeletal site-specific fashion and identified orofacial marrow stromal cells as unique cell populations. Further understanding of site-specific properties of hBMSCs and their impact on site-specific bone diseases and regeneration are needed. Published by Elsevier Inc. C1 Univ Penn, Sch Dent Med, Dept Oral Med, Robert Schattner Ctr, Philadelphia, PA 19104 USA. Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Akintoye, SO (reprint author), Univ Penn, Sch Dent Med, Dept Oral Med, Robert Schattner Ctr, Room 209 240 S 40th St, Philadelphia, PA 19104 USA. EM akintoye@dental.upenn.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 42 TC 131 Z9 137 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2006 VL 38 IS 6 BP 758 EP 768 DI 10.1016/j.bone.2005.10.027 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 055DB UT WOS:000238429100002 PM 16403496 ER PT J AU Bi, YM Nielsen, KL Kilts, TM Yoon, A Karsdal, MA Wimer, HF Greenfield, EM Heegaard, AM Young, MF AF Bi, YM Nielsen, KL Kilts, TM Yoon, A Karsdal, MA Wimer, HF Greenfield, EM Heegaard, AM Young, MF TI Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts SO BONE LA English DT Article DE biglycan; proteoglycan; osteoclast; osteolysis; ECM ID LEUKOCYTE PROTEASE INHIBITOR; BONE-RESORPTION; MICE LACKING; IN-VITRO; EXPRESSION; CELLS; GENE; OSTEOPOROSIS; OSTEOPONTIN; RAT AB Bone mass is maintained by a fine balance between bone formation by osteoblasts and bone resorption by osteoclasts. Although osteoblasts and osteoclasts have different developmental origins, it is generally believed that the differentiation, function, and survival of osteoclasts are regulated by osteogenic cells. We have previously shown that the extracellular matrix protein, biglycan (Bgn), plays an important role in the differentiation of osteoblast precursors. In this paper, we showed that Bgn is involved in regulating osteoclast differentiation through its effect on osteoblasts and their precursors using both in vivo and in vitro experiments. The in vivo osteolysis experiment showed that LPS (lipopolisaccharide)-induced osteolysis occurred more rapidly and extensively in bgn deficient mice compared to wild type (WT) mice. To further understand the mechanism of action, we determined the effects of Bgn on la, 25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3)-induced osteoclast differentiation and bone resorption in an co-culture of calvariae-derived pre-osteoblasts and osteoclast precursors derived from spleen or bone marrow. Time course and dose response experiments showed that tartrate-resistant acid phosphatase-positive multinuclear cells appeared earlier and more extensively in the co-cultures containing calvarial cells from bgn deficient mice than WT mice, regardless of the genotype of osteoclast precursors. The osteoblast abnormality that stimulated osteoclast formation appeared to be independent of the differential production of soluble RANKL and OPG and, instead, due to a decrease in osteoblast maturation accompanied by increase in osteoblastic proliferation. In addition to the imbalance between differentiation and proliferation, there was a differential decrease in secretory leukocyte protease inhibitor (slpi) in bgn deficient osteoblasts treated with 1,25-(OH)(2)D-3. These findings point to a novel molecular factor made by osteoblasts that could potentially be involved in LPS-induced osteolysis. Published by Elsevier Inc. C1 Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. Natl Univ Hosp, Finsen Ctr, Nordic Biosci AS, Copenhagen, Denmark. Natl Univ Hosp, Finsen Ctr, Dept Radiat Biol, Copenhagen, Denmark. Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. Smithsonian Inst, Natl Museum Nat Hist, Washington, DC 20560 USA. RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bldg 30 Room 225,MSC 4320,9000 Rockville Pike, Bethesda, MD 20892 USA. EM myoung@dir.nidcr.nih.gov FU Intramural NIH HHS NR 41 TC 45 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2006 VL 38 IS 6 BP 778 EP 786 DI 10.1016/j.bone.2005.11.005 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 055DB UT WOS:000238429100004 PM 16364709 ER PT J AU Lunemann, JD Edwards, N Muraro, PA Hayashi, S Cohen, JI Munz, C Martin, R AF Lunemann, JD Edwards, N Muraro, PA Hayashi, S Cohen, JI Munz, C Martin, R TI Increased frequency and broadened specificity of latent EBV nuclear antigen-I-specific T cells in multiple sclerosis SO BRAIN LA English DT Article DE multiple sclerosis; Epstein-Barr virus; T cell; autoimmunity ID EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MYELIN BASIC-PROTEIN; IMMUNE-RESPONSE; LYMPHOCYTES; EBNA1; MEMORY; RECOGNITION; ANTIBODIES; TH1 AB Epidemiological studies consistently demonstrate that patients with multiple sclerosis are almost universally infected with Epstein-Barr virus (EBV) and that the risk of developing the disease increases with the level of EBV-specific antibody titers. The EBV-encoded nuclear antigen-1 (EBNA1) maintains the viral episome in replicating infected human B cells, and EBNA1-specific CD4(+) T cells have been identified as a crucial part of the EBV-specific immune control in healthy individuals. We studied 20 untreated EBV seropositive patients with multiple sclerosis and 20 healthy EBV carriers matched demographically and for the expression of multiple sclerosis-associated HLA-DR alleles for their immunological control of EBV latency at the level of EBNA1-specific T cells. Using 51 overlapping peptides covering the C-terminal of EBNA I domain of EBNA1 (amino acids 400-641), peptide-specific CD4(+) memory T cells in patients with multiple sclerosis were found to be strikingly elevated in frequency, showed increased proliferative capacity and an enhanced interferon-gamma production. In contrast to EBNA1, T-cell responses to three other latent and three other lytic immunodominant EBV antigens and human cytomegalovirus (HCMV) epitopes did not differ between patients and controls, indicating a distinct role for EBNA1-specific T-cell responses in multiple sclerosis. CD4(+) T cells from healthy virus carriers preferentially recognized multiple epitopes within the centre part of the C-terminal, whereas the stimulatory epitopes in multiple sclerosis patients covered the entire sequence of this domain of EBNA1. Quantification of EBV viral loads in peripheral blood mononuclear cells (PBMC) by real-time polymerase chain reaction (PCR) showed higher levels of EBV copy numbers in some patients with multiple sclerosis, although the overall difference in viral loads was not statistically significant compared with healthy virus carriers. We suggest that the accumulation of highly antigen-sensitive EBNA1-specific Th1 cells in multiple sclerosis is capable of sustaining autoimmunity by cross-recognition of autoantigens or by TCR-independent bystander mechanisms. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD USA. Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD USA. Rockefeller Univ, Lab Viral Immunobiol, New York, NY USA. Humboldt Univ, Charite Univ Med Ctr, Div Neuroimmunol, Dept Neurol, Berlin, Germany. RP Lunemann, JD (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Cellular Immunol Sect, NIH, Bldg 10,Room 5B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM jlunemann@rockefeller.edu RI Lunemann, Jan/G-8729-2011; OI Lunemann, Jan/0000-0002-3007-708X; Muraro, Paolo/0000-0002-3822-1218 FU Intramural NIH HHS; NCI NIH HHS [R01CA108609] NR 50 TC 132 Z9 134 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUN PY 2006 VL 129 BP 1493 EP 1506 DI 10.1093/brain/awl067 PN 6 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 052HN UT WOS:000238224900016 PM 16569670 ER PT J AU Tao-Cheng, JH Dosemeci, A Winters, CA Reese, TS AF Tao-Cheng, Jung-Hwa Dosemeci, Ayse Winters, Christine A. Reese, Thomas S. TI Changes in the distribution of calcium calmodulin-dependent protein kinase II at the presynaptic bouton after depolarization SO BRAIN CELL BIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; HIPPOCAMPAL-NEURONS; SUBCELLULAR-LOCALIZATION; NEUROTRANSMITTER RELEASE; POSTSYNAPTIC DENSITY; SYNAPTIC PLASTICITY; SNARE PROTEINS; ACTIVE ZONE; SYNAPSIN-I; PHOSPHORYLATION AB Phosphorylation of synapsin I by CaMKII has been reported to mobilize synaptic vesicles from the reserve pool. In the present study, the distributions of alpha-CaMKII and of synapsin I were compared in synaptic boutons of unstimulated and stimulated hippocampal neurons in culture by immunogold electron microscopy. CaMKII and synapsin I are located in separate domains in presynaptic terminals of unstimulated neurons. Label for alpha -CaMKII typically surrounds synaptic vesicle clusters and is absent from the inside of the cluster in control synapses. In contrast, intense labeling for synapsin I is found within the vesicle clusters. Following 2 minutes of depolarization in high K+, synaptic vesicles decluster and CaMKII label disperses and mingles with vesicles and synapsin I. These results indicate that, under resting conditions, CaMKII has limited access to the synapsin I in synaptic vesicle clusters. The peripheral distribution of CaMKII around vesicle clusters suggests that CaMKII-mediated declustering progresses from the periphery towards the center, with the depth of penetration into the synaptic vesicle cluster depending on the duration of CaMKII activation. Depolarization also promotes a significant increase in CaMKII immunolabel near the presynaptic active zone. Activity-induced redistribution of CaMKII leaves it in a position to facilitate phosphorylation of additional presynaptic proteins regulating neurotransmitter release. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. RP Reese, TS (reprint author), NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. EM treese@mbl.edu FU Intramural NIH HHS NR 34 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1559-7105 J9 BRAIN CELL BIOL JI Brain Cell Biol. PD JUN PY 2006 VL 35 IS 2-3 BP 117 EP 124 DI 10.1007/s11068-007-9012-5 PG 8 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 223WQ UT WOS:000250406600002 PM 17957478 ER PT J AU Dignam, JJ Wieand, K Johnson, KA Raich, P Anderson, SJ Somkin, C Wickerham, DL AF Dignam, JJ Wieand, K Johnson, KA Raich, P Anderson, SJ Somkin, C Wickerham, DL TI Effects of obesity and race on prognosis in lymph node-negative, estrogen receptor-negative breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE competing risks; black women; estrogen receptor negative; obesity; prognosis ID SURGICAL ADJUVANT BREAST; YOUNG AFRICAN-AMERICAN; BOWEL PROJECT NSABP; BODY-MASS-INDEX; TUMOR CHARACTERISTICS; WHITE WOMEN; WEIGHT-GAIN; SEQUENTIAL METHOTREXATE; RACIAL DISPARITIES; MENOPAUSAL STATUS AB Background. Several factors may contribute to poorer prognosis for obese breast cancer patients, including unfavorable disease features, the influence of fat on estrogen availability, co-morbidity, and socio-demographic factors. Both obesity and estrogen receptor negative (ER-) tumors are more prevalent in black women than in whites in North America. We evaluated obesity and race in relation to outcomes in women with ER-breast cancer. Methods. Among 4077 women from National Surgical Adjuvant Breast and Bowel Project clinical trials for node-negative, ER-breast cancer, we evaluated disease-free survival (DFS) and its constituents (tumor recurrence, contralateral breast cancer (CBC), second primary cancers, deaths prior to these events) and mortality in relation to body mass index (BMI) and race, using statistical modeling to account for other prognostic factors. Results. Compared to those of normal weight (BMI <= 24.9), DFS hazard was greater for obese (BMI >= 30) women [hazard ratio (HR)=1.16, 95% confidence interval (CI)=1.01-1.33]. Obesity did not increase recurrence hazard, but did influence CBC (HR=2.08, 95% CI=1.22-3.55 in postmenopausal women) and second cancers (HR=1.49, 95% CI=1.06-2.10). Mortality increased with obesity; when partitioned by likely cause, those with BMI >= 35.0 had greater risk of non-breast cancer mortality (HR=1.86, 95% CI=1.21-2.84). Relative to whites and adjusted for BMI, black women had greater hazard for DFS (HR=1.17, 95% CI=1.00-1.38), CBC (HR=1.37, 95% CI=0.94-1.99), and non-breast cancer deaths (HR=2.10, 95% CI=1.45-3.03); risk for deaths likely due to breast cancer was closer to that in whites (HR=1.18; 95% CI=0.93-1.50). Conclusions. For women with node-negative, ER-breast cancer from clinical trials, obesity did not increase recurrence risk, but was associated with greater risk for second cancers, CBC, and mortality, particularly non-breast cancer deaths. Less favorable prognosis for black women persists in clinical trials, and is in part attributable to non-breast cancer outcomes. C1 Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. NCI, Div Canc Prevent, Breast & Gynecol Canc Res Grp, Bethesda, MD USA. AMC Canc Res Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NSABP, Ctr Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Kaiser Permanente, Div Res, Oakland, CA USA. NSABP Operat Ctr, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Dignam, JJ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. EM jdignam@health.bsd.uchicago.edu OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [NCI-U10-CA-69651, NCI P30-CA-14599, NCI-R03-CA-99508, NCI-U10-CA-12027] NR 52 TC 58 Z9 58 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JUN PY 2006 VL 97 IS 3 BP 245 EP 254 DI 10.1007/s10549-005-9118-3 PG 10 WC Oncology SC Oncology GA 056BX UT WOS:000238497100004 PM 16331345 ER PT J AU Castle, AL Fiehn, O Kaddurah-Daouk, R Lindon, JC AF Castle, Arthur L. Fiehn, Oliver Kaddurah-Daouk, Rima Lindon, John C. TI Metabolomics Standards Workshop and the development of international standards for reporting metabolomics experimental results SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE metabolomics; metabonomics; minimum information standards; metabolic profiling ID METABONOMIC TOXICOLOGY; PLANT METABOLOMICS; MASS-SPECTROMETRY; DATA-MANAGEMENT; DATA SETS; NMR; RECOMMENDATIONS; SPECTROSCOPY; ACIDS; REPRESENTATION AB Informatics standards and controlled vocabularies are essential for allowing information technology to help exchange, manage, interpret and compare large data collections. In a rapidly evolving field, the challenge is to work out how best to describe, but not prescribe, the use of these technologies and methods. A Metabolomics Standards Workshop was held by the US National Institutes of Health (NIH) to bring together multiple ongoing standards efforts in metabolomics with the NIH research community. The goals were to discuss metabolomics workflows (methods, technologies and data treatments) and the needs, challenges and potential approaches to developing a Metabolomics Standards Initiative that will help facilitate this rapidly growing field which has been a focus of the NIH roadmap effort. This report highlights specific aspects of what was presented and discussed at the 1st and 2nd August 2005 Metabolomics Standards Workshop. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Gen Ctr, Davis, CA USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, Biol Chem Sect, London, England. RP Castle, AL (reprint author), NIDDK, NIH, 6707 Democracy Blvd,Room 791,MSC 5460, Bethesda, MD 20892 USA. EM castlea@mail.nih.gov NR 60 TC 45 Z9 47 U1 4 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JUN PY 2006 VL 7 IS 2 BP 159 EP 165 DI 10.1093/bib/bbl008 PG 7 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 090PX UT WOS:000240964300005 PM 16772263 ER PT J AU Arons, E Sunshine, J Suntum, T Kreitman, RJ AF Arons, E Sunshine, J Suntum, T Kreitman, RJ TI Somatic hypermutation and VH gene usage in hairy cell leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE immunoglobulin; marginal zone; germline; rearrangements; germinal centre ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MARGINAL ZONE LYMPHOMA; VARIABLE-REGION GENES; HEAVY-CHAIN DIVERSITY; B-CELL; VILLOUS LYMPHOCYTES; ANTIGEN SELECTION; SPLENIC LYMPHOMA; H GENES; PROLYMPHOCYTIC LEUKEMIA AB To examine the usage and mutational status of VH genes in hairy cell leukaemia (HCL), we analysed 24 immunoglobulin heavy chain (IgH) sequences expressed in 23 patients. None had premature stop codons. VH3-23 was the most common gene and a VH6 gene was observed for the first time in HCL. Although the mean mutation frequency was 6.1%, slightly higher than in previous HCL series, four patients had 99.6-100% homology to germline sequences, three of whom had high tumour burdens and poor outcomes. Despite the high mutation frequency, only two of 24 rearrangements had clear statistical evidence of antigen-dependent somatic mutation. Our results increase the database of reported functional HCL rearrangements to 94 in 92 patients. Overall, both gene usage and mutation frequency are very similar to mucosa-associated lymphoid tissue-type marginal zone lymphoma. The data are consistent with HCL originating from post-germinal centre marginal zone B cells, although the heterogeneity observed suggests that HCL may originate differently in some patients, and this could have implications for prognosis and treatment. C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS NR 50 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2006 VL 133 IS 5 BP 504 EP 512 DI 10.1111/j.1365-2141.2006.06066.x PG 9 WC Hematology SC Hematology GA 036ZL UT WOS:000237116400004 PM 16681637 ER PT J AU Scheinberg, P Nunez, O Wu, C Young, NS AF Scheinberg, P Nunez, O Wu, C Young, NS TI Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE aplastic anaemia; anti-thymocyte globulin; ciclosporin; mycophenolate mofetil; pancytopenia ID STEM-CELL TRANSPLANTATION; HOST-DISEASE PROPHYLAXIS; ANTITHYMOCYTE GLOBULIN; ANTILYMPHOCYTE GLOBULIN; MARROW-TRANSPLANTATION; LONG-TERM; INDUCTION; EFFICACY; RECIPIENTS; THERAPY AB Severe aplastic anaemia (SAA) can be successfully treated with immunosuppressive therapies or haematopoietic stem cell transplantation (HSCT). Response rates with horse anti-thymocyte globulin (h-ATG) plus ciclosporin (CsA) are about 60-70%, and robust responders have an excellent long-term survival. We introduced a third immunosuppressive agent to standard h-ATG/CsA, mycophenolate mofetil (MMF), in an attempt to improve the response rate and survival, and to decrease the relapse rate and clonal evolution to myelodysplasia. A total of 104 consecutive patients with SAA were treated with h-ATG/CsA/MMF between May 1999 and June 2003 at the National Institutes of Health Clinical Center. The overall response rate at 6 months was 62%, with 24 (37% of responders) patients relapsing at a median of 389 d from ATG. Nine patients showed evidence of clonal evolution following ATG. After a median follow up of 42 months, the median survival among responders was not reached and among non-responders was 58 months. Over half of the relapses occurred during MMF administration. Despite a strong theoretical rationale for its use, MMF did not result in the improvement of response or relapse rates when compared with historical standard h-ATG/CsA. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr,Dr,Bldg 10 CRC,Rm 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@nhlbi.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS NR 23 TC 72 Z9 87 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2006 VL 133 IS 6 BP 606 EP 611 DI 10.1111/j.1365-2141.2006.06085.x PG 6 WC Hematology SC Hematology GA 043MR UT WOS:000237605700003 PM 16704434 ER PT J AU Scheinberg, P Nunez, O Young, NS AF Scheinberg, P Nunez, O Young, NS TI Retreatment with rabbit anti-thymocyte globulin and ciclosporin for patients with relapsed or refractory severe aplastic anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE aplastic anaemia; anti-thymocyte globulin; ciclosporin; refractory; relapse ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; TOTAL-BODY IRRADIATION; SAA WORKING PARTY; ANTITHYMOCYTE GLOBULIN; ANTILYMPHOCYTE GLOBULIN; IMMUNOSUPPRESSIVE TREATMENT; THERAPY; CYCLOPHOSPHAMIDE; THYMOGLOBULIN AB The management of patients with severe aplastic anaemia (SAA) who do not have a matched sibling donor and fail a course of horse anti-thymocyte globulin (h-ATG)/ciclosporin (CsA) is uncertain. Repeated courses of ATG-based immunosuppression are often employed; in children and increasingly in adults, alternative donor haematopoietic stem cell transplantation is an option. We analysed the success rate of retreatment with rabbit ATG (r-ATG)/CsA in 43 patients treated at our institution in the last 5 years; 22 were refractory (20 adults; two children) to h-ATG/CsA-based regimens and 21 (17 adults; four children) had relapsed after h-ATG/CsA-based regimens. The overall response rate was 30% in patients who were refractory to h-ATG and 65% in patients who had relapsed following h-ATG. The 1000-d survival in patients who responded to r-ATG was 90% compared with 65% in non-responders. Six patients developed a clonal haematological disorder; two were responders, two were non-responders and in two the evolution occurred before the response could be assessed at 3 months following r-ATG. Thirteen patients died; three were responders, six were non-responders and four patients died prior to 3 months when response was assessed. In our study, the response rate in refractory patients was inferior to what has been previously reported. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Rm 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@nhlbi.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS NR 19 TC 84 Z9 98 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 2006 VL 133 IS 6 BP 622 EP 627 DI 10.1111/j.1365-2141.2006.06098.x PG 6 WC Hematology SC Hematology GA 043MR UT WOS:000237605700005 PM 16704436 ER PT J AU Leavitt, SA AF Leavitt, Sarah A. TI "A private little revolution": The home pregnancy test in American culture SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Article DE home pregnancy test; women's health movement; hCG; online survey AB The home pregnancy test went from novelty to norm in twenty-five years. This article explores its cultural impact in the context of the women's health movement. Though women had long made do without it, the "private little revolution," as the test was called in an early advertisement, enabled them to take control of their reproductive health care and moved the moment of discovery from the doctor's office (back) to the home. The article introduces the test, explores its acceptance by physicians and by women, looks at the marketing of the test by drug companies, and traces its use in movies, television, and novels. C1 NIH, Off NIH Hist, Bethesda, MD 20892 USA. RP Leavitt, SA (reprint author), NIH, Off NIH Hist, Bldg 31,Room 5B38, Bethesda, MD 20892 USA. EM leavitts@mail.nih.gov NR 51 TC 14 Z9 14 U1 1 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0007-5140 EI 1086-3176 J9 B HIST MED JI Bull. Hist. Med. PD SUM PY 2006 VL 80 IS 2 BP 317 EP 345 DI 10.1353/bhm.2006.0064 PG 29 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 052ND UT WOS:000238239500005 PM 16809866 ER PT J AU Linehan, WM AF Linehan, W. Marston TI Identification of the genes for kidney cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE kidney; cancer; VHL; von Hippel Lindau; Met; BHD; fumarate hydratase ID HOGG-DUBE-SYNDROME; TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; VONHIPPEL-LINDAU DISEASE; HEREDITARY LEIOMYOMATOSIS; FUMARATE-HYDRATASE; MUTATIONS; FAMILIES; NEOPLASIA; SPECTRUM C1 NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bldg 10 CRC,Room 1-5940, Bethesda, MD 20892 USA. EM WML@nih.gov NR 26 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2006 VL 5 IS 6 BP 696 EP 699 PG 4 WC Oncology SC Oncology GA 075UA UT WOS:000239909500031 PM 16775424 ER PT J AU Bluhm, EC Daniels, J Pollock, BH Olshan, AF AF Bluhm, EC Daniels, J Pollock, BH Olshan, AF TI Maternal use of recreational drugs and neuroblastoma in offspring: a report from the Children's Oncology Group (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE neuroblastoma; marijuana smoking; case-control studies; prenatal exposure delayed effects; maternal exposure ID ALCOHOL-CONSUMPTION; CRITICAL WINDOWS; MEDICATION USE; RISK-FACTORS; CANCER GROUP; MARIJUANA; LEUKEMIA; SMOKING; PREGNANCY; EXPOSURE AB Objective To evaluate whether maternal use of recreational drugs around conception and pregnancy influences the risk of childhood neuroblastoma. Methods Self-reported use of recreational drugs from one month prior to pregnancy until diagnosis was assessed among mothers of 538 children with neuroblastoma (diagnosed 1992-1994 and identified through the Children's Cancer Group and Pediatric Oncology Group) and 504 age-matched controls (identified by random-digit dialing). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for age at diagnosis and household income. Results Maternal use of any illicit or recreational drug around pregnancy was associated with an increased risk of neuroblastoma in offspring (OR = 1.82, 95% CI: 1.13, 3.00), particularly use of marijuana in the first trimester of pregnancy (OR = 4.75, 95% CI: 1.55, 16.48). Marijuana use in the month before pregnancy did not increase risk. The effect of gestational marijuana exposure was strongest in subjects diagnosed before age one. Evaluation of recreational drugs other than marijuana was limited by infrequent use, and analyses of drug use by fathers were not carried out due to missing data. Conclusions Maternal recreational drug use and marijuana use during pregnancy were associated with increased risk of neuroblastoma in offspring. Further examination of these drugs and the risk of childhood cancer is warranted. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Ctr Biostat & Epidemiol, San Antonio, TX USA. RP Bluhm, EC (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd MSC 7238, Bethesda, MD 20892 USA. EM bluhme@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA57004]; NIEHS NIH HHS [P30ES10126] NR 29 TC 16 Z9 16 U1 3 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2006 VL 17 IS 5 BP 663 EP 669 DI 10.1007/s10552-005-0580-3 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035DQ UT WOS:000236980800006 PM 16633913 ER PT J AU Rossing, MA Tang, MTC Flagg, EW Weiss, LK Wicklund, KG Weiss, NS AF Rossing, MA Tang, MTC Flagg, EW Weiss, LK Wicklund, KG Weiss, NS TI Body size and risk of epithelial ovarian cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE ovarian neoplasms; obesity; weight ID MASS INDEX; FOLLOW-UP; WEIGHT; HEIGHT; COHORT; WOMEN; OBESITY; AGE AB Objective We conducted a population-based case-control study of epithelial ovarian cancer in relation to measures of body size and adult weight change. In particular, we sought to characterize the independent relation of body weight at particular ages with risk. Methods In-person interviews were sought with 35-54 year-old female residents of metropolitan Atlanta, Seattle or Detroit diagnosed with ovarian cancer during 1994-1998, and with controls sampled from these populations. Information provided by 355 cases and 1,637 controls was analyzed using unconditional logistic regression. Results The risk among women in the top tenth, relative to women in the lowest fourth, of the distribution of body weight at age 18 years was 1.5 (95% confidence interval, 1.0-2.2); at age 30, 1.9 (1.2-2.9); and 5 years before the reference date, it was 2.1 (1.4-3.3). While our results did not substantiate risk elevations reported in previous studies among subsets of women (e.g., with particular histologic tumor subtypes or according to past oral contraceptive use), we noted a particularly increased risk among women who reported 10 or more pounds gained during their first year of oral contraceptive use. Conclusions Our findings suggest that risk of epithelial ovarian cancer may be most closely linked with body weight in the relatively recent past (but before the time in which the disease may manifest as weight loss) among women who develop this disease during the years before or shortly after menopause. C1 Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Emory Univ, Sch Med, Div Gen Med, Atlanta, GA USA. US NCI, Bethesda, MD USA. RP Rossing, MA (reprint author), Fred Hutchinson Canc Res Ctr, Program Epidemiol, POB 19024, Seattle, WA 98109 USA. EM mrossing@fhcrc.org FU NICHD NIH HHS [R01 HD32175] NR 22 TC 13 Z9 13 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUN PY 2006 VL 17 IS 5 BP 713 EP 720 DI 10.1007/s10552-006-0010-1 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035DQ UT WOS:000236980800012 PM 16633919 ER PT J AU Yang, YA Zhang, GM Feigenbaum, L Zhang, YE AF Yang, YA Zhang, GM Feigenbaum, L Zhang, YE TI Smad3 reduces susceptibility to hepatocarcinoma by sensitizing hepatocytes to apoptosis through downregulation of Bcl-2 SO CANCER CELL LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; BETA-INDUCED APOPTOSIS; HUMAN HEPATOCELLULAR-CARCINOMA; ACTIVATED PROTEIN-KINASE; TGF-BETA; TRANSGENIC MICE; TUMOR-SUPPRESSOR; GENE-MUTATIONS; C-MYC; EXPRESSION AB In the liver, derangement of TGF-beta signaling is associated with an increased incidence of hepatocellular carcinoma (HCC), but the mechanism is not clear. We report here that forced expression of a major TGF-beta signaling transducer, Smad3, reduces susceptibility to HCC in a chemically induced murine model. This protection is conferred by Smad3's ability to promote apoptosis by repressing Bcl-2 transcription in vivo through a GC-rich element in the Bcl-2 promoter. We also show that the proapoptotic activity of Smad3 requires both input from TGF-beta signaling and activation of p38 MAPK, which occurs selectively in the liver tumor cells. Thus, Smad3 enables the tumor suppression function of TGF-beta by serving as a physiological mediator of TGF-beta-induced apoptosis. C1 NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Anim Sci Program, Frederick, MD 21702 USA. RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM yingz@helix.nih.gov RI Zhang, Ying/G-3657-2015 OI Zhang, Ying/0000-0003-2753-7601 FU Intramural NIH HHS [Z01 BC010419-08] NR 68 TC 67 Z9 76 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2006 VL 9 IS 6 BP 445 EP 457 DI 10.1016/j.ccr.2006.04.025 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056HZ UT WOS:000238514400006 PM 16766264 ER PT J AU Davis, IJ Kim, JJ Ozsolak, F Widlund, HR Rozenblatt-Rosen, O Granter, SR Du, JY Fletcher, JA Denny, CT Lessnick, SL Linehan, WM Kung, AL Fisher, DE AF Davis, IJ Kim, JJ Ozsolak, F Widlund, HR Rozenblatt-Rosen, O Granter, SR Du, JY Fletcher, JA Denny, CT Lessnick, SL Linehan, WM Kung, AL Fisher, DE TI Oncogenic MITF dysregulation in clear cell sarcoma: Defining the MiT family of human cancers SO CANCER CELL LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; WAARDENBURG SYNDROME TYPE-2; SOFT PART SARCOMA; MALIGNANT-MELANOMA; GENE FUSION; TFE3 GENE; CHROMOSOME-TRANSLOCATION; EWS/ATF1 ONCOGENE; LINEAGE SURVIVAL; LEUCINE-ZIPPER AB Clear cell sarcoma (CCS) harbors a pathognomonic chromosomal translocation fusing the Ewing's sarcoma gene (EWS) to the CREB family transcription factor ATF1 and exhibits melanocytic features. We show that EWS-ATF1 occupies the MITF promoter, mimicking melanocyte-stimulating hormone (MSH) signaling to induce expression of MITF, the melanocytic master transcription factor and an amplified oncogene in melanoma. Knockdown/rescue studies revealed that MITF mediates the requirement of EWS-ATF1 for CCS survival in vitro and in vivo as well as for melanocytic differentiation. Moreover, MITF and TFE3 reciprocally rescue one another in lines derived from CCS or pediatric renal carcinoma. Seemingly unrelated tumors thus employ distinct strategies to oncogenically dysregulate the MiT family, collectively broadening the definition of MiT-associated human cancers. C1 Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif Los Angeles, Gwynne Hazen Cherry Mem Labs, Div Hematol Oncol, Dept Pediat, Los Angeles, CA 90095 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA100400, CA102309, K08 CA100400] NR 79 TC 91 Z9 96 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2006 VL 9 IS 6 BP 473 EP 484 DI 10.1016/j.ccr.2006.04.021 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 056HZ UT WOS:000238514400008 PM 16766266 ER PT J AU Maruvada, P Srivastava, S AF Maruvada, P Srivastava, S TI Joint National Cancer Institute-Food and Drug Administration Workshop on Research Strategies, Study Designs, and Statistical Approaches to Biomarker Validation for Cancer Diagnosis and Detection SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BIOSPECIMEN NETWORK; EARLY INTERVENTION; PREVENTION TRIAL; MARKERS; TESTS AB Cancer remains the second leading cause of death in the United States, in spite of tremendous advances made in therapeutic and diagnostic strategies. Successful cancer treatment depends on improved methods to detect cancers at early stages when they can be treated more effectively. Biomarkers for early detection of cancer enable screening of asymptomatic populations and thus play a critical role in cancer diagnosis. However, the approaches for validating biomarkers have yet to be addressed clearly. In an effort to delineate the ambiguities related to biomarker validation and related statistical considerations, the National Cancer Institute, in collaboration with the Food and Drug Administration, conducted a workshop in July 2004 entitled "Research Strategies, Study Designs, and Statistical Approaches to Biomarker Validation for Cancer Diagnosis and Detection." The main objective of this workshop was to review basic considerations underpinning the study designs, statistical methodologies, and novel approaches necessary to rapidly advance the clinical application of cancer biomarkers. The current commentary describes various aspects of statistical considerations and study designs for cancer biomarker validation discussed in this workshop. C1 NCI, Div Canc Prevent, Canc Biomarkers Res Grp, NIH, Bethesda, MD 20892 USA. RP Srivastava, S (reprint author), NCI, Div Canc Prevent, Canc Biomarkers Res Grp, NIH, Execut Plaza N,Room 3142,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM ss1a@nih.gov NR 25 TC 27 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1078 EP 1082 DI 10.1158/1055-9965.EPI-05-0432 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100005 PM 16775163 ER PT J AU Lim, U Weinstein, S Albanes, D Pietinen, P Teerenhovi, L Taylor, PR Virtamo, J Stolzenberg-Solomon, R AF Lim, U Weinstein, S Albanes, D Pietinen, P Teerenhovi, L Taylor, PR Virtamo, J Stolzenberg-Solomon, R TI Dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma and multiple myeloma in a cohort of male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; ALCOHOL-CONSUMPTION; ALTERS SUSCEPTIBILITY; MALIGNANT-LYMPHOMA; HISTOLOGIC SUBTYPE; CANCER REGISTRY; UNITED-STATES; RISK; FOLATE; POLYMORPHISMS AB Reported associations between genetic polymorphisms in folate-metabolizing enzymes and lymphoid malignancies suggest etiologic involvement of one-carbon metabolism and its related dietary exposures. We examined dietary factors of one-carbon metabolism in relation to non-Hodgkin lymphoma WHO and multiple myeloma (MM) among 27,111 healthy male smokers who completed baseline dietary questionnaires in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. During a follow-up of up to 16.4 years (19852001), 195 NHL and 32 MM cases were ascertained. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). There was no significant association between dietary folate and NHL (HR comparing fourth to first quartile, 1.03; 95% CI, 0.68-1.55). Dietary vitamin B-12 was inversely associated with NHL (HR, 0.61; 95% CI, 0.37-1.00; P-trend = 0.06). The inverse association of vitamin B-12 was evident for diffuse subtype but did not reach statistical significance. There were no significant associations of dietary vitamin B-6 Or B-2, methionine, or alcohol with NHL. None of the dietary or supplemental one-carbon nutrients were associated with MM, although the power of these analyses was limited. Our results suggest that high intake of vitamin B-12 among heavy smokers may be protective against NHL but warrant further studies, including among nonsmokers. C1 NCI, NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Univ Helsinki, Cent Hosp, Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. RP Stolzenberg-Solomon, R (reprint author), NCI, NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 320, Rockville, MD 20852 USA. EM stolzenr@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU CCR NIH HHS [N01-RC-37004, N01-RC-45035]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 40 TC 16 Z9 17 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1109 EP 1114 DI 10.1158/1055-9965.EPI-05-0918 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100009 PM 16775167 ER PT J AU Wu, K Giovannucci, E Byrne, C Platz, EA Fuchs, C Willett, WC Sinha, R AF Wu, K Giovannucci, E Byrne, C Platz, EA Fuchs, C Willett, WC Sinha, R TI Meat mutagens and risk of distal colon adenoma in a cohort of US men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINE CONTENT; COLORECTAL-CANCER RISK; VARYING DEGREES; CONSUMPTION; PRODUCTS; EXPOSURE; CARCINOGENS; REPRODUCIBILITY; VALIDITY AB Cooking meats at high temperatures and for long duration produces heterocyclic amines and other mutagens. These meat-derived mutagenic compounds have been hypothesized to increase risk of colorectal neoplasia, but prospective data are unavailable. We examined the association between intakes of the heterocyclic amines 2-amino-3,8-dimethylimidazo[4, 5,-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,4,8-trimethylimidazo [4,5,-f]quinoxaline (DiMeIQx), and meat-derived mutagenicity (MDM) and risk of distal colon adenoma using a cooking method questionnaire administered in 1996 in the Health Professionals Follow-up Study cohort. Between 1996 and 2002, 581 distal colon adenoma cases were identified. Higher intake of MDM was marginally associated with increased risk of distal adenoma [fourth versus lowest quintile: odds ratio (OR), 1.39; 95% confidence interval (95% CI), 1.05-1.84; highest versus lowest quintile: OR, 1.29; 95% CI, 0.97-1.72; P-trend = 0.08]. Adjusting for total red meat or processed meat intake did not explain those associations. Our data also suggested a positive association between higher MeIQx (highest versus lowest quintile: OR, 1.28; 95% CI, 0.95-1.71; P-trend = 0.22) and risk of adenoma, but this association was attenuated after adjusting for processed meat intake. DiMeIQx and PhIP did not seem to be associated with risk of adenoma. In conclusion, higher consumption of mutagens from meats cooked at higher temperature and longer duration may be associated with higher risk of distal colon adenoma independent of overall meat intake. Because mutagens other than heterocyclic amines also contribute to MDM, our results suggest that mutagens other than heterocyclic amines in cooked meats may also play a role in increasing the risk of distal adenoma. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Georgetown Univ, Lombardi Canc Ctr, Canc Genet & Epidemiol Program, Washington, DC USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. RP Wu, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Bldg 2,665 Huntington Ave, Boston, MA 02115 USA. EM kana.wu@channing.harvard.edu RI Sinha, Rashmi/G-7446-2015; Byrne, Celia/K-2964-2015 OI Sinha, Rashmi/0000-0002-2466-7462; Byrne, Celia/0000-0001-8289-4252 FU NCI NIH HHS [CA 55075, CA95589] NR 33 TC 59 Z9 60 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1120 EP 1125 DI 10.1158/1055-9965.EPI-05-0782 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100011 PM 16775169 ER PT J AU Gunter, MJ Canzian, F Landi, S Chanock, SJ Sinha, R Rothman, N AF Gunter, MJ Canzian, F Landi, S Chanock, SJ Sinha, R Rothman, N TI Inflammation-related gene polymorphisms and colorectal adenoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PPAR-GAMMA; INTERLEUKIN-1 POLYMORPHISMS; ULCERATIVE-COLITIS; PROMOTER VARIANT; ALPHA PROMOTER; RISK; CANCER; CYCLOOXYGENASE-2; TRANSCRIPTION; ASSOCIATION AB Chronic inflammation has been reported to be a risk factor for colorectal neoplasia. The propensity to mount an inflammatory response is modified by germ line variation in cytokine and other inflammation-related genes. We hypothesized that a proinflammatory genotype would be positively associated with colorectal adenoma, a precursor of colorectal cancer. We investigated the association of colorectal adenoma with 19 single nucleotide polymorphisms in a range of important proinflammatory (IL1B, IL6, IL8, TNF, and LTA) and anti-inflammatory (IL4, IL10, and IL13) cytokines and other inflammation-related genes (PTGS2 and PPARG) in a case-control study of risk factors for colorectal polyps in which all participants (ages 18-74 years) had undergone colonoscopy or sigmoidoscopy. The study sample comprised 244 cases of colorectal adenoma and 231 polyp-free controls. Compared with being homozygous for the common allele, heterozygosity at the IL1B -31 (C > T) locus was associated with an odds ratio (OR) for colorectal adenoma of 1.8 [95% confidence interval (95% CI), 1.2-2.9]. Homozygous carriers of the IL8 -251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 -251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4). Among non-nonsteroidal anti-inflammatory drug users, there was a statistically significant association between the IL10 -819-T/T genotype and adenoma compared with the common IL10 -819-C/C genotype (OR, 3.9; 95% CI, 1.1-13.6), which was not evident among nonsteroidal anti-inflammatory drug users (OR, 0.7; 95% CI, 0.3-1.5; P-interaction = 0.01). These exploratory data provide evidence that polymorphic variation in genes that regulate inflammation could alter risk for colorectal adenoma. C1 Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. IARC, Lyon, France. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ Pisa, Dept Biol & Genet, Pisa, Italy. RP Gunter, MJ (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mgunter@aecom.yu.edu RI Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Landi, Stefano/0000-0001-8364-6357 NR 37 TC 90 Z9 91 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1126 EP 1131 DI 10.1158/1055-9965.EPI-06-0042 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100012 PM 16775170 ER PT J AU Faupel-Badger, JM Prindiville, SA Venzon, D Vonderhaar, BK Zujewski, JA Eng-Wong, J AF Faupel-Badger, JM Prindiville, SA Venzon, D Vonderhaar, BK Zujewski, JA Eng-Wong, J TI Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MAMMARY EPITHELIAL-CELLS; POSTMENOPAUSAL WOMEN; SIGNAL-TRANSDUCTION; RANDOMIZED-TRIAL; SEX-HORMONES; TAMOXIFEN; ESTROGEN; ENDOCRINE; RECEPTOR; PREVENTION AB Background: Prolactin is a peptide hormone necessary for normal breast development that may contribute to breast tumorigenesis. Estrogen is a significant positive regulator of prolactin synthesis; therefore, raloxifene, a selective estrogen receptor modulator under study as a breast cancer prevention agent, may modulate both estradiol and prolactin levels by inhibiting estradiol from binding to its receptor. Methods: Premenopausal women at increased risk for invasive breast cancer participated in a pilot chemoprevention trial and were given 60 mg raloxifene daily for 24 months. Fasting serum samples collected at baseline and after 12 months on drug were used to measure circulating prolactin, estradiol, and sex hormone binding globulin (SHBG) levels. Results: Of the 27 subjects who completed 12 months of raloxifene, 23 had paired prolactin samples, and 20 had paired estradiol and SHBG samples. Prolactin levels did not significantly change with raloxifene treatment, but SHBG levels increased (mean change = 7.3 nmol/L; P = 0.0001; 95% confidence interval, 3.9-10.7). Estradiol (mean change = 42 pg/mL; P = 0.048; 95% confidence interval, 1-84 pg/mL) levels were elevated when comparing 15 of the 20 women with paired estradiol measurements who also had both of these samples taken during the early follicular phase of the menstrual cycle. Conclusions: This report is the first to examine the long-term effects of raloxifene on prolactin, estradiol, and SHBG levels in premenopausal women who are also at increased risk for developing invasive breast cancer. Raloxifene had no significant effect on prolactin levels but did increase estradiol and SHBG measurements. C1 NCI, Mammary Gland Biol & Tumorigenesis Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Canc Res Ctr, Bethesda, MD 20892 USA. RP Faupel-Badger, JM (reprint author), NCI, Mammary Gland Biol & Tumorigenesis Lab, Canc Res Ctr, Bldg 37,Room 1106,37 Convent Dr, Bethesda, MD 20892 USA. EM badgerje@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU Intramural NIH HHS NR 43 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1153 EP 1158 DI 10.1158/1055-9965.EPI-05-0898 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100017 PM 16775175 ER PT J AU Boffetta, P Clark, S Shen, M Gislefoss, R Peto, R Andersen, A AF Boffetta, P Clark, S Shen, M Gislefoss, R Peto, R Andersen, A TI Serum cotinine level as predictor of lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SELF-REPORTED SMOKING; ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; BIOCHEMICAL MARKERS; PASSIVE SMOKING; EXPOSURE; WOMEN; CONSUMPTION; VALIDATION; NICOTINE AB Background: No prospective studies are available on serum cotinine level as a marker of lung cancer risk. Methods: We analyzed serum cotinine level among 1,741 individuals enrolled since the 1970s in a prospective study of Norwegian volunteers who developed lung cancer during the follow-up and 1,741 matched controls free from lung cancer. Serum cotinine was measured with a competitive immunoassay. Regression dilution was corrected for based on repeated measures on samples from 747 subjects. Results: Mean serum cotinine level was higher in cases than in controls. Compared with subjects with a cotinine level of <= 5 ng/mL, the odds ratio of lung cancer was increasing linearly, reaching 55.1 (95% confidence interval, 35.7-85.0) among individuals with a serum cotinine level of > 378 ng/mL. There was no clear suggestion of a plateau in risk at high exposure levels. Odds ratios were very similar in men and women. We found no association between serum cotinine level (range, 0.1-9.9 ng/mL) and lung cancer risk among self-reported nonsmokers and long-term quitters (79 cases and 350 controls). Discussion: The association between tobacco smoking and lung cancer risk might be stronger than is estimated from questionnaire-based studies. Serum cotinine level is a predictor of risk of lung cancer among smokers. The reported plateau in risk at high doses is likely due mainly to artifacts. There is no difference between men and women in the carcinogenicity of tobacco smoking. C1 IARC, F-69008 Lyon, France. Canc Registry Norway, Oslo, Norway. Univ Oxford, Clin Trial Serv Unit, Oxford, England. NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. RP Boffetta, P (reprint author), IARC, 150 Cours Albert Thomas, F-69008 Lyon, France. EM boffetta@iarc.fr NR 37 TC 51 Z9 53 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1184 EP 1188 DI 10.1158/1055-9965-EPI-06-0032 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100021 PM 16775179 ER PT J AU McGlynn, KA Tarone, RE El-Serag, HB AF McGlynn, KA Tarone, RE El-Serag, HB TI A comparison of trends in the incidence of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEPATITIS-C VIRUS; LIVER-CANCER; INFECTION; CIRRHOSIS; EPIDEMIOLOGY; COHORT; RATES; PREVALENCE; MORTALITY; RADIATION AB The incidence rates of liver cancers, both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing in the U.S. It is possible that the increases are related to common exposures, and if so, similar trends in incidence by gender, age, ethnicity, and calendar period, might exist. To examine this hypothesis, age-specific trends in the incidence of HCC and ICC in the Surveillance, Epidemiology and End Results program (1976-2000) were examined by year of diagnosis and year of birth. Age-period-cohort models were also fit to the data. The incidence of HCC in the most recent time period was twice as high among Black men (8.8/100,000) and women (2.6/100,000) as among White men (4.6/100,000) and women (1.2/100,000). However, between 1976 and 2000, incidence among all four ethnic- and gender-specific groups increased by > 90% (White males, 123.2%; White females, 96.8%; Black males, 97.9%; Black females, 91.9%) with young White men experiencing the greatest increases (432%). In contrast, ICC rates were similar for Black (0.93/100,000) and White men (0.92/100,000), but higher for White (0.57/100,000) than Black women (0.39/ 100,000). Although ICC incidence increased among all groups, the increase was greatest for Black men (138.5%), followed by White men (124.4%), White women (111.1%), and Black women (85.7%) Age-period-cohort analyses of HCC revealed a significant cohort effect among younger men (45-65 years old), but not older men (65-84 years old), suggesting possible differences in etiology. In conclusion, the rates of HCC and ICC approximately doubled between 1976 and 2000. Trends by age, gender, ethnicity, and birth cohort suggest that heterogeneity exists in the factors influencing these rates. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20854 USA. NCI, Int Epidemiol Inst, NIH, Dept Hlth & Human Serv, Rockville, MD 20854 USA. Baylor Coll Med, Houston, TX 77030 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS-7060,6120 Execut Blvd, Rockville, MD 20854 USA. EM mcglynnk@mail.nih.gov FU Intramural NIH HHS NR 38 TC 121 Z9 123 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1198 EP 1203 DI 10.1158/1055-99965-EPI-05-0811 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100023 PM 16775181 ER PT J AU Ahn, JY Nowell, S McCann, SE Yu, JH Carter, L Lang, NP Kadlubar, FF Ratnasinghe, LD Ambrosone, CB AF Ahn, Jiyoung Nowell, Susan McCann, Susan E. Yu, Jihnhee Carter, Lisa Lang, Nicholas P. Kadlubar, Fred F. Ratnasinghe, Luke D. Ambrosone, Christine B. TI Associations between catalase phenotype and genotype: Modification by epidemiologic factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROMOTER REGION; LIPID-PEROXIDATION; PROSTATE-CANCER; BREAST-CANCER; GENE; POLYMORPHISM; SUSCEPTIBILITY; ANTIOXIDANTS; BIOMARKER; OXIDANTS AB Catalase is an endogenous antioxidant enzyme that neutralizes hydrogen peroxide and is induced by oxidative challenge. A -262C -> T polymorphism in the promoter region of the gene (CAT) is associated with risk of several conditions related to oxidative stress. We sought to determine the functional effects of the CAT polymorphism on enzyme activity in erythrocytes and the potential modifying effects of demographic and lifestyle factors on genotype/ phenotype relationships, using specimens and data from controls from breast and prostate cancer studies in Arkansas (n = 420). There was a dose-response reduction in catalase activity by genotype, with geometric means of 115.4 units/mg hemoglobin for those with CC genotypes, 82.1 units/mg for those with CT genotypes, and 73.5 units/mg for those with TT genotypes. Associations were only observed among Caucasians (P < 0.0001), with no effects among African Americans (P = 0.91), and were stronger among women than men, although numbers in stratified analyses were small. Differences in catalase activity by genotype were most pronounced among those in the highest tertiles of consumption of fruits and vegetables (-35%, P = 0.003), with weaker relationships among those who were lower consumers (-21.8%, P = 0.16). Among those with CC genotypes, there was no change in activity by consumption, but there were notable decreases in activity by tertiles of consumption for those with at least one T allele. These data indicate that the CAT -262C -> T polymorphism predicts a portion of catalase phenotype, which may be limited to Caucasians. Associations between genotype and phenotype were modified by dietary factors, illustrating the biochemical complexity of studies of genetic polymorphisms and disease risk. C1 Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Biostat, New York, NY USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NZH, Bethesda, MD USA. RP Ambrosone, CB (reprint author), Roswell Pk Canc Inst, Dept Epidemiol, Elm & Carlton St, Buffalo, NY 14263 USA. EM christine.ambrosone@roswellpark.org FU NCI NIH HHS [R01 CA095222]; NIA NIH HHS [R01 AG15722-03] NR 20 TC 65 Z9 67 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2006 VL 15 IS 6 BP 1217 EP 1222 DI 10.1158/1055-9965.EPI-06-0104 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053IZ UT WOS:000238300100026 PM 16775184 ER PT J AU Cunningham, SC Gallmeier, E Hucl, T Dezentje, DA Calhoun, ES Falco, G Abdelmohsen, K Gorospe, M Kern, SE AF Cunningham, SC Gallmeier, E Hucl, T Dezentje, DA Calhoun, ES Falco, G Abdelmohsen, K Gorospe, M Kern, SE TI Targeted deletion of MKK4 in cancer cells: A detrimental phenotype manifests as decreased experimental metastasis and suggests a counterweight to the evolution of tumor-suppressor loss SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; PATHWAY; BREAST; GENE; TUMORIGENESIS; MUTATIONS AB Tumor-suppressors have commanded attention due to the selection for their inactivating mutations in human tumors. However, relatively little is understood about the inverse, namely, that tumors do not select for a large proportion of seemingly favorable mutations in tumor-suppressor genes. This could be explained by a detrimental phenotype accruing in a cell type-specific manner to most cells experiencing a biallelic loss. For example, MKK4, a tumor suppressor gene distinguished by a remarkably consistent mutational rate across diverse tumor types and an unusually high rate of loss of heterozygosity, has the surprisingly low rate of genetic inactivation of only similar to 5%. To explore this incongruity, we engineered a somatic gene knockout of MKK4 in human cancer cells. Although the null cells resembled the wild-type cells regarding in vitro viability and proliferation in plastic dishes, there was a marked difference in a more relevant in vivo model of experimental metastasis and tumorigenesis. MKK4(-/-) clones injected i.v. produced fewer lung metastases than syngeneic MKK4-competent cells (P = 0.0034). These findings show how cell type-specific detrimental phenotypes can offer a paradoxical and yet key counterweight to the selective advantage attained by cells as they experiment with genetic null states during tumorigenesis, the resultant balance then determining the observed biallelic mutation rate for a given tumor-suppressor gene. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Res Ctr, Dept Oncol, Baltimore, MD 21231 USA. Univ Maryland Med Syst, Dept Surg, Baltimore, MD USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kern, SE (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Canc Res Ctr, Dept Oncol, Canc Res Bldg 464,1650 Orleans St, Baltimore, MD 21231 USA. EM sk@jhmi.edu OI abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS; NCI NIH HHS [CA 62924] NR 21 TC 29 Z9 34 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5560 EP 5564 DI 10.1158/0008-5472.CAN-06-0555 PG 5 WC Oncology SC Oncology GA 049GC UT WOS:000238003100007 PM 16740690 ER PT J AU Toretsky, JA Erkizan, V Levenson, A Abaan, OD Parvin, JD Cripe, TP Rice, AM Lee, SB Uren, A AF Toretsky, JA Erkizan, V Levenson, A Abaan, OD Parvin, JD Cripe, TP Rice, AM Lee, SB Uren, A TI Oncoprotein EWS-FLI1 activity is enhanced by RNA helicase A SO CANCER RESEARCH LA English DT Article ID PRIMITIVE NEUROECTODERMAL TUMOR; EWINGS-SARCOMA; POLYMERASE-II; CHROMOSOME-TRANSLOCATION; TRANSCRIPTIONAL COACTIVATOR; FUSION PROTEINS; HELA-CELLS; GENE; TARGET; FAMILY AB RNA helicase A (RHA), a member of the DEXH box helicase family of proteins, is an integral component of protein complexes that regulate transcription and splicing. The EWS-FLI1 oncoprotein is expressed as a result of the chromosomal translocation t(11;22) that occurs in patients with the Ewing's sarcoma family of tumors (ESFT). Using phage display library screening, we identified an EWS-FLI1 binding peptide containing homology to RHA. ESFT cell lines and patient tumors highly expressed RRA. GST pull-down and ELISA assays showed that EWS-FLI1 specifically bound RHA fragment amino acids 630 to 1020, which contains the peptide region discovered by phage display. Endogenous RHA was identified in a protein complex with EWS-FLI1 in ESFT cell lines. Chromatin inummoprecipitation experiments showed both EWS-FLI1 and RHA bound to EWS-FLI1 target gene promoters. RHA stimulated the transcriptional activity of EWS-FLI1 regulated promoters, including Id2, in ESFT cells. In addition, RIIA expression in mouse embryonic fibroblast cells stably transfected with EWS-FLI1 enhanced the anchorage-independent phenotype above that with EWS-FLI1 alone. These results suggest that RHA interacts with EWS-FLI1 as a transcriptional cofactor to enhance its function. C1 Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Harvard Univ, Sch Med, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. RP Toretsky, JA (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Res Bldg,Room W316,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM jat42@georgetown.edu RI ERKIZAN, HAYRIYE VERDA/C-2341-2011; Parvin, Jeffrey/C-8955-2009 FU NCI NIH HHS [CA88004, R01 CA088004, R01 CA088004-08]; NCRR NIH HHS [RR14567]; NIGMS NIH HHS [GM53504] NR 44 TC 65 Z9 69 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5574 EP 5581 DI 10.1158/0008-5472.CAN-05-3293 PG 8 WC Oncology SC Oncology GA 049GC UT WOS:000238003100009 PM 16740692 ER PT J AU Aprelikova, O Wood, M Tackett, S Chandramouli, GVR Barrett, JC AF Aprelikova, O Wood, M Tackett, S Chandramouli, GVR Barrett, JC TI Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; FACTOR 1-ALPHA; BREAST-CANCER; PROLYL HYDROXYLATION/; O-2 HOMEOSTASIS; LYSYL OXIDASE; HIF-ALPHA; EXPRESSION; VHL; HIF-2-ALPHA AB Tumor hypoxia often directly correlates with aggressive phenotype, metastasis progression, and resistance to chemotherapy. Two transcription factors [hypoxia-inducible factor-1 alpha (HIF-1 alpha) and HIF-2 alpha] are dramatically induced in hypoxic areas and regulate the expression of genes necessary for tumor adaptation to the conditions of low oxygen; however, the relative contribution of these factors is controversial. We used RNA interference-mediated inactivation of HIF-1 alpha or HIF-2 alpha followed by microarray analysis to identify genes specifically regulated by either HIF-1 or HIF-2 in hypoxia. We found that, in the MCF7 cell line, the vast majority of hypoxia-responsive genes (> 80%) were dependent on the presence of HIF-1 alpha. However, a small group of genes were preferentially regulated by HIF-2 alpha. Promoter analysis for this group of genes revealed that all of them have putative binding sites for ETS family transcription factors, and 10 of 11 HIF-2 alpha-dependent genes had at least one potential hypoxia-responsive element (HRE) in proximity to an ETS transcription factor binding site. Knockdown of ELK-1, the most often represented member of ETS family, significantly reduced hypoxic induction of the HIF-2 alpha-dependent genes. Physical and functional interaction between ELK-1 and HIF-2 alpha were supported by coimmunoprecipitation of these two proteins, luciferase reporter assay using CITED2 promoter, and binding of ELK-1 protein to the promoters of CITED2 and WISP2 genes in proximity to a HRE. These data suggest that the choice of the target genes by HIF-1 or HIF-2 depends on availability and cooperation of HIFs with other factors recognizing their cognate elements in the promoters. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Aprelikova, O (reprint author), NCI, Lab Biosyst & Canc, NIH, Bldg 37,Room 1044,9000 Rockville Pike, Bethesda, MD 20892 USA. EM apreliko@mail.nih.gov OI Tackett, Sean/0000-0001-5369-7225 FU Intramural NIH HHS NR 43 TC 103 Z9 108 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5641 EP 5647 DI 10.1158/0008-5472.CAN-05-3345 PG 7 WC Oncology SC Oncology GA 049GC UT WOS:000238003100018 PM 16740701 ER PT J AU Voo, KS Zeng, G Mu, JB Zhou, JH Su, XZ Wang, RF AF Voo, KS Zeng, G Mu, JB Zhou, JH Su, XZ Wang, RF TI CD4+ T-cell response to mitochondrial cytochrome b in human melanoma SO CANCER RESEARCH LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; COMPLEX-III DEFICIENCY; TUMOR-ANTIGEN; EXERCISE INTOLERANCE; MALIGNANT-MELANOMA; ANTITUMOR IMMUNITY; CD8-T-CELL MEMORY; CD4-T-CELL HELP; SELF-PEPTIDE; MUTATIONS AB Mitochondrial DNA (mtDNA) is highly susceptible to mutations due to the low level of DNA repair and the presence of a high level of reactive oxygen species in the organelle. Although mtDNA mutations have been implicated in degenerating diseases, aging, and cancer, very little is known about the role of T cells in immunosurveillance for mtDNA aberrations. Here, we describe T-cell recognition of a peptide translated from an alternative open reading frame of the mitochondrial cytochrome b (cyt b) gene in melanoma cells established from a patient. To understand how the cyt b gene is transcribed and translated in tumor cells, we found that cyt b-specific CD4(+) T cells only recognized protein fractions derived from cytoplasm and not from mitochondria. However, T-cell recognition of tumor cells could be inhibited by treatment of tumor cells with rhodamine 6G inhibitor, which depletes mitochondria. These findings suggest that cyt b mRNA is leaked out of the mitochondria and then translated in the cytoplasm for presentation to CD4(+) T cells. The cyt b cDNAs from this patient contain highly heteroplasmic transition mutations compared with control cell lines, suggesting a compromise of mitochondrial integrity that may have contributed to melanoma induction or progression. These findings provide the first example of a mitochondrial immune target for CD4(+) T cells and therefore have implications for the immunosurveillance of mitochondrial aberrations in cancer patients. C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Urol Oncol, Los Angeles, CA USA. NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Wang, RF (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, Alkek Bldg,N1120,1 Baylor Pl, Houston, TX 77030 USA. EM rongfuw@bcm.tmc.edu FU NCI NIH HHS [P50 CA093459, R01 CA101795, R01 CA90327] NR 42 TC 11 Z9 11 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2006 VL 66 IS 11 BP 5919 EP 5926 DI 10.1158/0008-5472.CAN-05-4574 PG 8 WC Oncology SC Oncology GA 049GC UT WOS:000238003100049 PM 16740732 ER PT J AU Pogribny, IP Ross, SA Tryndyak, VP Pogribna, M Poirier, LA Karpinets, TV AF Pogribny, Igor P. Ross, Sharon A. Tryndyak, Volodymyr P. Pogribna, Marta Poirier, Lionel A. Karpinets, Tatiana V. TI Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4-2Oh2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats SO CARCINOGENESIS LA English DT Article ID DNA METHYLATION; GENOMIC HYPOMETHYLATION; PRENEOPLASTIC LIVER; GENE-EXPRESSION; HUMAN CANCERS; HUMAN-TUMORS; H19 GENE; HETEROCHROMATIN; EPIGENETICS; REGION AB The field of cancer epigenetics has received much attention in recent years. However, the relationship of cancer epigenetics with cancer etiology is not clear. Recent studies suggest the involvement of altered DNA methylation and histone modifications in the emergence of epigenetically reprogrammed cells with specific tumor-related phenotypes at premalignant stages of tumor development. In this study, we used a methyl-deficient model of rodent hepatocarcinogenesis to examine the roles of DNA, histone H3 lysine 9 and histone H4 lysine 20 methylation, and the level of the expression of Suv39h1 and Suv4-2Oh2 histone methyltransferases in the carcinogenic process. We demonstrated that the development of liver tumors was characterized by progressive demethylation of DNA repeats, decrease in histone H4 lysine 20 trimethylation, and a gradual decrease in the expression of Suv4-2Oh2 histone methyltransferase. A prominent increase in the trimethylation of histone H3 lysine 9 and in the expression of Suv39h1 histone methyltransferase was observed in preneoplastic nodules and liver tumors indicating the promotional role of these epigenetic alterations at later stages of carcinogenesis. The appearance of tumor-specific epigenetic alterations (demethylation of repetitive elements, loss of histone H4 lysine 20 trimethylation, altered expression of Suv4-2Oh2 and Suv39h1 histone methyltransferases) at preneoplastic stages of hepatocarcinogenesis provides experimental support for the epigenetic hypothesis of tumorigenesis that considers stress-induced epigenetic reprogramming of the cell as an important prerequisite to succeeding mutations. C1 NCTR, Jefferson, AR 72078 USA. NCI, Bethesda, MD 20892 USA. Univ Tennessee, Knoxville, TN 37996 USA. RP Pogribny, IP (reprint author), NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ipogribny@nctr.fda.gov NR 55 TC 77 Z9 84 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 JUN PY 2006 VL 27 IS 6 BP 1180 EP 1186 DI 10.1093/carcin/bgi364 PG 7 WC Oncology SC Oncology GA 060QM UT WOS:000238816700009 PM 16497704 ER PT J AU Grubbs, CJ Lubet, RA Atigadda, VR Christov, K Deshpande, AM Tirmal, V Xia, G Bland, KI Eto, I Brouillette, WJ Muccio, DD AF Grubbs, Clinton J. Lubet, Ronald A. Atigadda, Venkatram R. Christov, Konstantin Deshpande, Anil M. Tirmal, Vivek Xia, Gang Bland, Kirby I. Eto, Isao Brouillette, Wayne J. Muccio, Donald D. TI Efficacy of new retinoids in the prevention of mammary cancers and correlations with short-term biomarkers SO CARCINOGENESIS LA English DT Article ID 6-S-TRANS-RETINOIC ACID ANALOGS; NUCLEAR RECEPTOR-BINDING; 9-CIS-RETINOIC ACID; BREAST-CANCER; X-RECEPTOR; CHEMOPREVENTIVE ACTIVITY; TRANSCRIPTIONAL ACTIVITY; TRANSGENIC MICE; COMBINATION; LGD1069 AB A number of retinoid X receptor (RXR) agonists have proven to be highly effective in preventing methylnitrosourea (MNU) induced mammary cancers. However, these agonists have side effects; particularly causing an increase in serum triglyceride levels. A series of ligands for RXR were designed based on computer modeling to the ligand binding domain (LBD) of the RXR receptors and on structure-activity relationships. The chemopreventive effects of these retinoids were evaluated in the relatively long-term MNU model. As a short-term assay to predict their efficacy, the ability of the retinoids to modulate cell proliferation and apoptosis was also determined in mammary cancers after only 7 days of treatment. The five UAB retinoids evaluated included two Class I UAB retinoids (UAB20, UAB112) and three Class II UAB retinoids (UAB30, 4-methyl-UAB30 and the benzosuberone-analog of UAB30). The previously evaluated RXR agonist targretin and the pan-agonist 9-cis-retinoic acid (9-cis-RA), which interacts with both RAR and RXR receptors, were included as positive agonists known to prevent cancer in the MNU model. In the prevention studies, in which the agents were administered beginning 5 days after MNU until the end of the study, targretin (150 mg/kg diet) and 4-methyl-UAB30 (200 mg/kg diet) were highly effective in decreasing cancer numbers by 75-85%. UAB30 (200 mg/kg diet) and 9-cis-RA (60 mg/kg diet) gave intermediate inhibitions of 60 and 45%, respectively. Targretin (15 mg/kg diet), UAB20 (200 mg/kg diet) and the benzosuberone analog of UAB30 (200 mg/kg diet) showed limited activity by decreasing cancer multiplicity 25-30%, while UAB112 had no effect on mammary cancer multiplicity. A direct correlation was observed between the long-term chemopreventive efficacy of these agents and their ability to decrease cell proliferation in mammary cancers after short-term treatment. Furthermore, the highly effective agents (4-methyl-UAB30 and targretin at 150 mg/kg diet) increased apoptosis 3-5 times, while agents with moderate or limited preventive efficacy failed to significantly increase apoptosis. Although the more effective retinoid treatments increased serum triglycerides 2.5- to 4.0-fold, one moderately effective agent (UAB30) had no significant effect on lipid levels. In summary, a short-term in vivo method has been identified for screening newly synthesized retinoids both for chemopreventive efficacy and for their adverse effect on serum triglycerides. C1 Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Chem, Birmingham, AL 35294 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Illinois, Dept Surg Oncol, Chicago, IL USA. RP Grubbs, CJ (reprint author), Univ Alabama, Dept Surg, G78D Volker Hall,1530 3rd Ave S, Birmingham, AL 35294 USA. EM clinton.grubbs@ccc.uab.edu FU NCI NIH HHS [N01-CN-05118-MAO]; PHS HHS [HHSN261200433001C] NR 29 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2006 VL 27 IS 6 BP 1232 EP 1239 DI 10.1093/carcin/bgi308 PG 8 WC Oncology SC Oncology GA 060QM UT WOS:000238816700015 PM 16344269 ER PT J AU Sakoda, LC Gao, YT Chen, BE Chen, J Rosenberg, PS Rashid, A Deng, J Shen, MC Wang, BS Han, TQ Zhang, BH Cohen-Webb, H Yeager, M Welch, R Chanock, S Fraumeni, JF Hsing, AW AF Sakoda, Lori C. Gao, Yu-Tang Chen, Bingshu E. Chen, Jinbo Rosenberg, Philip S. Rashid, Asif Deng, Jie Shen, Ming-Chang Wang, Bing-Sheng Han, Tian-Quan Zhang, Bai-He Cohen-Webb, Hope Yeager, Meredith Welch, Robert Chanock, Stephen Fraumeni, Joseph F., Jr. Hsing, Ann W. TI Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk biliary tract cancer and gallstones: a population-based study in Shanghai, China SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LUNG-CANCER; CYCLOOXYGENASE-2 GENE; COMMON POLYMORPHISM; GALLBLADDER; EXPRESSION; ASSOCIATION; SYNTHASE-2; TESTS; TUMOR AB There is evidence that chronic inflammation predisposes to biliary tract cancer and that use of non-steroidal antiinflammatory drugs (NSAIDs) is protective. Although the mechanisms by which NSAIDs lower cancer risk remain unclear, NSAIDs reduce prostaglandin production by blocking prostaglandin-endoperoxide synthase 2 (PTGS2, commonly known as COX-2), an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue. Since variants in the PTGS2 gene may modify the expression or function of its encoded enzyme to modulate the inflammatory response in the biliary tract, we examined the associations of eight PTGS2 polymorphisms (-645C -> T; Ex3 -8G -> C; IVS5 -275T -> G; IVS7 + 111T -> C; Ex10 + 127T -> C; Ex10 + 686 -> ATTAT -> TTATA; Ex10 + 837T -> C; Ex10 -90C -> T) with biliary tract cancer and stones in a population-based case-control study conducted in Shanghai, China. Genotyping was performed for 411 patients with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater), 895 patients with biliary stones (673 gallbladder, 222 bile duct), and 786 healthy individuals randomly selected from the population. Significant associations were seen only between the Ex10 + 837T -> C marker and bile duct cancer risk. Relative to individuals with the TT genotype, those carrying the C allele (TC or CC genotype) had a 1.8-fold (95% confidence interval: 1.2-2.7) risk of bile duct cancer. Inferred haplotypes including this risk-conferring allele were also associated with increased bile duct cancer risk of similar magnitude. Our results suggest that a common PTGS2 variant increases bile duct cancer risk. Further investigation is needed to confirm and extend our findings in studies of biliary tract cancer that more comprehensively examine PTGS2 and other inflammation-related genes. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. MD Anderson Canc Ctr, Dept Pathol, Houston, TX USA. Shanghai Tumor Hosp, Shanghai, Peoples R China. Zhongshan Hosp, Shanghai, Peoples R China. Fudan Univ, Shanghai 200433, Peoples R China. Shanghai Med Univ 2, Ruijin Hosp, Dept Surg, Shanghai, Peoples R China. Second Mil Med Univ, Inst Oriental Hepatobiliary Surg, Shanghai, Peoples R China. Westat Corp, Rockville, MD USA. NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. RP Sakoda, LC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7067, Bethesda, MD 20892 USA. EM sakodal@mail.nih.gov FU Intramural NIH HHS NR 32 TC 40 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2006 VL 27 IS 6 BP 1251 EP 1256 DI 10.1093/carcin/bgi314 PG 6 WC Oncology SC Oncology GA 060QM UT WOS:000238816700018 PM 16361272 ER PT J AU Jindal, G Friedman, M Locklin, J Wood, BJ AF Jindal, G Friedman, M Locklin, J Wood, BJ TI Palliative radiofrequency ablation for recurrent prostate cancer SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE palliation; prostate cancer; radiofrequency ablation ID METASTASES INVOLVING BONE; FEASIBILITY; COMPLICATIONS; THERMOMETRY; MULTICENTER; SAFETY; PAIN AB Percutaneous radiofrequency ablation (RFA) is a minimally invasive local therapy for cancer. Its efficacy is now becoming well documented in many different organs, including liver, kidney, and lung. The goal of RFA is typically complete eradication of a tumor in lieu of an invasive surgical procedure. However, RFA can also play an important role in the palliative care of cancer patients. Tumors which are surgically unresectable and incompatible for complete ablation present the opportunity for RFA to be used in a new paradigm. Cancer pain runs the gamut from minor discomfort relieved with mild pain medication to unrelenting suffering for the patient, poorly controlled by conventional means. RFA is a tool which can potentially palliate intractable cancer pain. We present here a case in which RFA provided pain relief in a patient with metastatic prostate cancer with pain uncontrolled by conventional methods. C1 NIH, Diagnost Radiol Dept, Bethesda, MD 20892 USA. RP Locklin, J (reprint author), NIH, Diagnost Radiol Dept, Room 1C 659,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM locklinj@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 16 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JUN PY 2006 VL 29 IS 3 BP 482 EP 485 DI 10.1007/s00270-004-0200-8 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 032CK UT WOS:000236751300030 PM 16010507 ER PT J AU Kehat, Z Heinrich, R Ben-Izhak, O Miyazaki, H Gutkind, JS Aronheim, A AF Kehat, Zhak Heinrich, Ronit Ben-Izhak, Ofer Miyazaki, Hiroshi Gutkind, J. Silvio Aronheim, Ami TI Inhibition of basic leucine zipper transcription is a major mediator of atrial dilatation SO CARDIOVASCULAR RESEARCH LA English DT Article DE trial function; hypertrophy; connexins; gene expression ID JUN DIMERIZATION PROTEIN-2; ELEMENT-BINDING PROTEIN; TRANSGENIC MICE; CONDUCTION ABNORMALITIES; C-JUN; ATRIOVENTRICULAR-BLOCK; GENE-EXPRESSION; SUDDEN-DEATH; FIBRILLATION; HEART AB Objective: Atrial fibrillation is the most prevalent clinically significant cardiac arrhythmia. Atrial dilatation, a predictor of atrial fibrillation, is thought to result from increased ventricular pressure. However, the underlying molecular mechanisms responsible for atrial dilatation are largely unknown. Here we sought to examine whether the expression of a basic leucine zipper inhibitor protein, JDP2, in the heart is sufficient for the generation of atrial dilatation. Methods: A tetracycline-regulated transgene was used to express JDP2 specifically in the mouse heart. Mice hearts were dissected and subjected to Northern and Western analysis, or analyzed by ECG recording and echocardiography. Regulation of gene expression was studied using electromobility shift assays and luciferase gene reporter analysis. Results: Expression of JDP2 resulted in massive bi-atrial dilatation, defects in conduction, and a lethal phenotype. These effects were developmentally independent, acquired during adulthood, and were reversible upon abolishing of JDP2 expression. Connexin 40 and myosin light chain 2a expression were identified as potential target genes. Conclusion: Expression of basic leucine zipper transcription inhibitors is sufficient to results in atrial dilatation. This dilatation is acquired postnatally and is reversible. Thus, basic leucine zipper transcription inhibitors may be a relevant therapeutic target for preventing atrial dilatation and atrial fibrillation. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Technion Israel Inst Technol, Rappaport Fac Med, Dept Mol Genet, IL-31096 Haifa, Israel. Rambam Med Ctr, Dept Internal Med C & Cardiol, Haifa, Israel. Rambam Med Ctr, Dept Pathol, Haifa, Israel. Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA USA. NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Aronheim, A (reprint author), Technion Israel Inst Technol, Rappaport Fac Med, Dept Mol Genet, 7 Efron St, IL-31096 Haifa, Israel. EM aronheim@tx.technion.ac.il RI Gutkind, J. Silvio/A-1053-2009 NR 39 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUN 1 PY 2006 VL 70 IS 3 BP 543 EP 554 DI 10.1016/j.cardiores.2006.02.018 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053JY UT WOS:000238302600016 ER PT J AU Mattiussi, S Matsumoto, K Illi, B Martelli, F Capogrossi, MC Gaetano, C AF Mattiussi, S Matsumoto, K Illi, B Martelli, F Capogrossi, MC Gaetano, C TI Papilloma protein E6 abrogates shear stress-dependent survival in human endothelial cells: Evidence for specialized functions of paxillin SO CARDIOVASCULAR RESEARCH LA English DT Article DE flow; signal transduction; apoptosis; endothelial; integrin ID APOPTOSIS; FORCES; PHOSPHORYLATION; MECHANISMS; INTEGRINS; ADHESION; RELEASE; BINDING; KINASE; SITES AB Background: To investigate how endothelial cells transduce intracellular signals in response to laminar shear stress (SS), we made use of the papilloma virus oncoprotein E6 which interacts with and induces degradation of numerous cellular proteins including p53 and members of the PDZ-domain family. E6 also recognizes paxillin (PX-N), a fundamental component of focal adhesions, interfering with its association to focal adhesion kinase (FAK). Methods and results: Human umbilical vein endothelial cells, expressing E6 or its mutated variant Delta E6(105-110) (Delta E6) which does not inactivate p53, were cultured under static conditions or exposed to a laminar SS of 12 dyn/cm(2) for 16h. In response to SS, cells expressing E6 or Delta E6 failed to synthesise nitric oxide and directionally remodel their cytoskeleton, as indicated by morphology and phalloidin staining of actin microfilaments. Under these conditions, PXN association with FAK, its localization to the plasma membrane, and its phosphorylation on tyrosine-31, which partially encompasses the PX-N/FAK docking site, were severely compromised. These alterations were paralleled by the impairment of important SS-dependent endothelial functions, including nitric oxide production and survival upon serum deprivation. The direct targeting of PXN expression by RNA interference partially reproduced the E6 phenotype, impairing flow-dependent cell orientation and survival but not nitric oxide production. Conclusions: These results provide evidence that papilloma virus E6 protein interferes with the function of the SS-mechanosensor and suggests a potential a role for PXN in this process. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Ist Dermopat Immacolata, Lab Patol Vasc, I-00167 Rome, Italy. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Ist Cardiol, Lab Biol Vasc & Terapia Gen, Milan, Italy. RP Gaetano, C (reprint author), Ist Dermopat Immacolata, Lab Patol Vasc, Via Monti Creta 104, I-00167 Rome, Italy. EM gaetano@idi.it OI Martelli, Fabio/0000-0002-8624-7738; Gaetano, Carlo/0000-0002-5238-1832 NR 32 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JUN 1 PY 2006 VL 70 IS 3 BP 578 EP 588 DI 10.1016/j.cardiores.2006.02.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 053JY UT WOS:000238302600019 PM 16624261 ER PT J AU Xie, A Walker, NJ Wang, DS AF Xie, An Walker, Nigel J. Wang, Desuo TI Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) enhances triggered afterdepolarizations in rat ventricular myocytes SO CARDIOVASCULAR TOXICOLOGY LA English DT Article DE TCDD; cardiac action potential; triggered activity; afterdepolarizations; transient outward current; ventricular arrhythmia AB The effects of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on action potential and afterdepolarizations were studied in rat ventricular myocytes using nystatin-perforated whole-cell patch-clamp technique. TCDD treatment, in the concentration range of 1 to 100 nM, significantly prolonged action potential duration measured at 90% of repolarization (APD(90)). The triggered delayed-afterdepolarizations (DADs) were observed in 6 out of 8 cells after exposure of TCDD (10 nM). In the presence of isoproterenol (ISO, 10 nM) or Bay K 8644 (1 mu M), TCDD (10 nM) markedly augmented the amplitude and frequency of the arrhythmogenic DADs and triggered sustained spontaneous firings in ventricular myocytes. Voltage-clamp data indicated that TCDD (10 nM) exposure significantly enhanced the transient inward current (I(ti)). The triggered early-afterdepolarizations (EADs) were evoked only in cells simultaneously exposed to TCDD (10 nM) and ISO (or Bay K 8644). Further study indicated that TCDD treatment increased L-type Ca(2+) current. These results indicate that activation of TCDD signaling pathway can prolong action potential duration and cause abnormal triggered afterdepolarizations. These effects may lead to clinically relevant ventricular arrhythmia especially when susceptible individuals are under elevated sympathetic stress or suffering from other myocardiopathies coincided with Ca(2+)-overload. C1 [Xie, An; Wang, Desuo] Univ S Carolina, S Carolina Coll Pharm, Dept Basic Pharmaceut Sci, Columbia, SC 29208 USA. [Walker, Nigel J.] Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC USA. RP Wang, DS (reprint author), 715 Sumter St, Columbia, SC 29208 USA. EM wang@cop.sc.edu RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z01 ES046004-21]; NIEHS NIH HHS [5 K22 ES00367, K22 ES000367] NR 59 TC 8 Z9 8 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1530-7905 J9 CARDIOVASC TOXICOL JI Cardiovasc. Toxicol. PD JUN PY 2006 VL 6 IS 2 BP 99 EP 110 DI 10.1385/CT:6:2:99 PG 12 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA V44NR UT WOS:000203009900003 PM 17303918 ER PT J AU Wu, D Asiedu, M Adelstein, RS Wei, QZ AF Wu, D Asiedu, M Adelstein, RS Wei, QZ TI A novel guanine nucleotide exchange factor MyoGEF is required for cytokinesis SO CELL CYCLE LA English DT Article DE MyoGEF; non-muscle myosin II; RhoA; Rac1; cytokinesis; GTPase signaling ID BINDING PROTEIN-RHO; MYOSIN-II; CONTRACTILE RING; HELA-CELLS; CLEAVAGE FURROW; DICTYOSTELIUM; EXPRESSION; GTPASES; RAC; LOCALIZATION AB The cleavage furrow is created by an actomyosin contractile ring that is regulated by small GTPase proteins such as Rac1 and RhoA. Guanine nucleotide exchange factors (GEFs) are positive regulators of the small GTPase proteins and have been implicated as important factors in regulating cytokinesis. However, it is still unclear how GEFs regulate the contractile ring during cytokinesis in mammalian cells. Here we report that a novel GEF, which is termed MyoGEF (myosin-interacting GEF), interacts with non-muscle myosin II and exhibits activity toward RhoA. MyoGEF and non-muscle myosin II colocalize to the cleavage furrow in early anaphase cells. Disruption of MyoGEF expression in U2OS cells by RNA interference (RNAi) results in the formation of multinucleated cells. These results suggest that MyoGEF, RhoA, and non-muscle myosin II act as a functional unit at the cleavage furrow to advance furrow ingression during cytokinesis. C1 Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Wei, QZ (reprint author), Kansas State Univ, Dept Biochem, 104 Willard Hall, Manhattan, KS 66506 USA. EM weiq@ksu.edu OI Adelstein, Robert/0000-0002-8683-2144 FU NCRR NIH HHS [P20 RR-17708, P20 RR017708, P20 RR017708-030018, P20 RR017708-057360]; NHLBI NIH HHS [K22 HL071542, K22 HL071542-01, K22 HL071542-02] NR 30 TC 27 Z9 29 U1 1 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2006 VL 5 IS 11 BP 1234 EP 1239 DI 10.4161/cc.5.11.2815 PG 6 WC Cell Biology SC Cell Biology GA 057FG UT WOS:000238581100020 PM 16721066 ER PT J AU Szczepanowska, J Korn, ED Brzeska, H AF Szczepanowska, J Korn, ED Brzeska, H TI Activation of myosin in HeLa cells causes redistribution of focal adhesions and F-actin from cell center to cell periphery SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE myosin II; myosin light chain; p21-activated kinase; PAK; catalytic domain; phosphorylation ID HEAVY-CHAIN KINASE; REGULATORY LIGHT-CHAIN; RHO-ASSOCIATED KINASE; P21-ACTIVATED KINASE; PROTEIN-KINASE; STRESS FIBERS; MORPHOLOGICAL-CHANGES; CATALYTIC DOMAIN; MAMMALIAN-CELLS; PAK AB Activation of actomyosin II by phosphorylation of its regulatory light chain is one of the main factors involved in the regulation of cytoskeletal dynamics. Phosphorylation of myosin regulatory light chain may be mediated directly and indirectly by several kinases including myosin light chain kinase (MLCK) and kinases activated by small GTP-binding proteins. Most of the myosin kinases, including PAK, can also interact with other proteins through binding sites located outside of their catalytic domains. In an attempt to study the effects due only to phosphorylation of myosin light chain, we expressed the constitutively active catalytic domain of ameba PAK in HeLa cells. The catalytic domain phosphorylates myosin light chain in vitro with high specific activity but has none of the sequences that target mammalian PAK to other proteins and membranes. Expression of the catalytic domain caused disassembly of focal adhesions and stress fibers in the cell center and accumulation of focal adhesions and F-actin at the cell periphery. There was a twofold increase in the phosphorylation level of endogenous myosin light chain and changes in cell shape consistent with enhanced cell contractility. The phenotype was independent of MLCK, ROCK, MEK, Rac, and Rho activities but was abolished by blebbistatin, a specific inhibitor of myosin II activity. Our data are consistent with myosin being directly phosphorylated by the expressed catalytic domain of ameba PAK with the induced phenotype resulting from cell retraction driven by contraction of peripheral actomyosin. The phenotype induced by expression of the catalytic domain is reminiscent of that caused by expression of active mammalian PAK, suggesting that myosin phosphorylation may play an important role in PAK-induced cytoskeletal changes. The catalytic domain of ameba PAK may be a useful tool for studying the effects of myosin light chain phosphorylation in other cells. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Brzeska, H (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2515, Bethesda, MD 20892 USA. EM brzeska@helix.nih.gov RI Korn, Edward/F-9929-2012 NR 61 TC 13 Z9 14 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD JUN PY 2006 VL 63 IS 6 BP 356 EP 374 DI 10.1002/cm.20125 PG 19 WC Cell Biology SC Cell Biology GA 046DQ UT WOS:000237792000004 PM 16607629 ER PT J AU Michelini, M Franceschini, V Chen, SS Papini, S Rosellini, A Ciani, F Margolis, L Revoltella, RP AF Michelini, M Franceschini, V Chen, SS Papini, S Rosellini, A Ciani, F Margolis, L Revoltella, RP TI Primate embryonic stem cells create their own niche while differentiating in three-dimensional culture systems SO CELL PROLIFERATION LA English DT Article ID EXTRACELLULAR-MATRIX; ADHESION; FIBRONECTIN; BINDING; EMBRYOGENESIS; COMPLEXES; CADHERINS AB Rhesus monkey embryonic stem cells (ESCs) (R366.4), cultured on a three-dimensional (3D) collagen matrix with or without human neonatal foreskin fibroblasts (HP1.1) as feeder cells, or embedded in the collagen matrix, formed complex tubular or spherical gland-like structures and differentiated into phenotypes characteristic of neural, epithelial and endothelial lineages. Here, we analysed the production of endogenous extracellular matrix (ECM) proteins, cell-cell adhesion molecules, cell-surface receptors, lectins and their glycoligands, by differentiating ESCs, forming a micro-environment, a niche, able to positively influence cell behaviour. The expression of some of these molecules was modulated by HP1.1 cells while others were unaffected. We hypothesized that both soluble factors and the niche itself were critical in directing growth and/or differentiation of ESCs in this 3D environment. Creating such an appropriate experimental 3D micro-environment, further modified by ESCs and modulated by exogenous soluble factors, may constitute a template for adequate culture systems in developmental biology studies concerning differentiation of stem cells. C1 CNR, Inst Biomed Technol, I-56100 Pisa, Italy. Univ Bologna, Dept Evolut & Expt Biol, I-40126 Bologna, Italy. NICHD, NASA, NIH, Ctr 3 Dimens Tissue Culture, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Revoltella, RP (reprint author), CNR, Inst Biomed Technol, Via G Moruzzi 1, I-56100 Pisa, Italy. EM r.revoltella@imd.pi.cnr.it NR 45 TC 17 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0960-7722 J9 CELL PROLIFERAT JI Cell Prolif. PD JUN PY 2006 VL 39 IS 3 BP 217 EP 229 DI 10.1111/j.1365-2184.2006.00381.x PG 13 WC Cell Biology SC Cell Biology GA 037XA UT WOS:000237179900005 PM 16671999 ER PT J AU Pazgier, M Hoover, DM Yang, D Lu, W Lubkowski, J AF Pazgier, M Hoover, DM Yang, D Lu, W Lubkowski, J TI Human beta-defensins SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE human beta-defensin; innate and adaptive immunity; antimicrobial and chemotactic activity; beta-defensin structure; structure-function relationship ID NF-KAPPA-B; NATURAL PEPTIDE ANTIBIOTICS; MACROPHAGE INFLAMMATORY PROTEIN-3-ALPHA; MONOCYTE CHEMOTACTIC PROTEIN-1; HELICAL ANTIMICROBIAL PEPTIDES; RESPIRATORY EPITHELIAL-CELLS; MULTIPLE SIGNALING PATHWAYS; HUMAN BETA-DEFENSIN-1 GENE; TRUNCATED ALPHA-DEFENSINS; HUMAN AIRWAY EPITHELIA AB The last decade led to the discovery and characterization of several human beta-defensins. Analysis of genomic information indicates that the number of beta-defensin-like molecules encoded by the human genome may number in the tens. Growing interest in beta-defensins steadily enhances our knowledge about various aspects of their gene location, expression patterns and the transcription factors involved in their regulation in vivo. The hallmark property of beta-defensins, their antimicrobial activity, is clearly only the tip of the iceberg in the extensive network of inter-relations within the immune system in which these peptides function. Structural studies of beta-defensins provide the molecular basis for a better understanding of their properties, functions and their potential for practical applications. In this review, we present some recent advances in the studies of human beta-defensins, with an emphasis on possible correlations between their structural and functional properties. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. NIH, Ctr Informat Technol, Sci Comp Branch, Bethesda, MD 20892 USA. NCI, Lab Mol Immunoregulat, Canc Res Ctr, Basic Res Program,SAIC Frederick Inc, Ft Detrick, MD 21702 USA. Univ Maryland, Inst Human Virol, Inst Biotechnol, Baltimore, MD 21201 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM jacek@ncifcrf.gov RI Lu, Wuyuan/B-2268-2010; Pazgier, Marzena/B-7295-2012 NR 241 TC 260 Z9 286 U1 3 U2 18 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUN PY 2006 VL 63 IS 11 BP 1294 EP 1313 DI 10.1007/s00018-005-5540-2 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 056NR UT WOS:000238531500008 PM 16710608 ER PT J AU Chen, KQ Huang, J Gong, WH Zhang, LZ Yu, PC Wang, JM AF Chen, Keqiang Huang, Jian Gong, Wanghua Zhang, Lingzhi Yu, Peichu Wang, Ji Ming TI CD40/CD40L Dyad in the Inflammatory and Immune Responses in the Central Nervous System SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE CD40; CD40 ligand; signal transduction; amyloid beta; mFPR2; Alzheimer's disease AB CD40 and its cognate ligand (CD40L) are a pair of regulators of pro-inflammatory and immune responses. In the central nervous system (CNS), CD40 is expressed on a variety of cells, including vascular endothelial cells, smooth muscle cells, astrocytes and microglia (the brain macrophages, being the most sensitive cell type to respond to CD40 ligand). Interaction between CD40 on microglia and CD40L presented by infiltrating T lymphocytes and other resident CNS cells triggers a series of intracellular signaling events that promote the production of a wide array of cytokines, chemokines and neurotoxins. Thus, both molecules serve as amplifiers of pro-inflammatory and immune responses in the CNS and constitute important molecular targets for therapeutic intervention of diseases. C1 [Chen, Keqiang; Huang, Jian; Yu, Peichu] Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 201101, Peoples R China. [Chen, Keqiang; Zhang, Lingzhi; Wang, Ji Ming] Natl Canc Inst, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. [Gong, Wanghua] Natl Canc Inst, SAIC, Basic Res Program, Frederick, MD 21702 USA. RP Chen, KQ (reprint author), Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 201101, Peoples R China. EM kchen@mail.ncifcrf.gov NR 43 TC 42 Z9 44 U1 0 U2 4 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD JUN PY 2006 VL 3 IS 3 BP 163 EP 169 PG 7 WC Immunology SC Immunology GA V32BH UT WOS:000208926200001 PM 16893496 ER PT J AU Li, T Tsuda, Y Minoura, K In, Y Ishida, T Lazarus, LH Okada, Y AF Li, Tingyou Tsuda, Yuko Minoura, Katsuhiko In, Yasuko Ishida, Toshimasa Lazarus, Lawrence H. Okada, Yoshio TI Enantioselective synthesis of a phenylalanine library containing alkyl groups on the aromatic moiety: Confirmation of stereostructure by X-ray analysis SO CHEMICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE phenylalanine analogue; asymmetrical hydrogenation; L-configuration; enzymatic digestion; X-ray analysis ID OPIOID RECEPTOR AFFINITY; ASYMMETRIC-SYNTHESIS; AMINO-ACIDS; ANALOGS; SELECTIVITY; DMP; DERIVATIVES; PEPTIDES; RESIDUE; DESIGN AB Six phenylalanine analogues containing 2'-methyl-, 2',6'-dimethyl-, 2'-ethyl-6'-methyl-, 2'-isopropyl-6'methyl-, 2',4',6'-trimethyl-, and 3',5'-dimethyl-L-phenylalanine were synthesized enantioselectively through asymmetric hydrogenation of acetamidoacrylate derivatives. Enzymatic digestion and X-ray analysis supported the L-configuration of the phenylalanine derivatives obtained. C1 Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, Fac Pharmaceut Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. Osaka Univ Pharmaceut Sci, Takatsuki, Osaka 5691094, Japan. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Med Chem Grp, Res Triangle Pk, NC 27709 USA. RP Okada, Y (reprint author), Kobe Gakuin Univ, Grad Sch Food & Med Sci, Nishi Ku, Kobe, Hyogo 6512180, Japan. EM okada@pharm.kobegakuin.ac.jp FU Intramural NIH HHS NR 26 TC 12 Z9 15 U1 0 U2 2 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0009-2363 J9 CHEM PHARM BULL JI Chem. Pharm. Bull. PD JUN PY 2006 VL 54 IS 6 BP 873 EP 877 DI 10.1248/cpb.54.873 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 055SH UT WOS:000238470200021 PM 16755061 ER PT J AU Belluscio, L AF Belluscio, L. TI Development and activity-dependent refinement of the olfactory intrabulbar map SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 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 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A1 EP A1 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600010 ER PT J AU Ishimaru, Y Okada, S Naito, H Nagai, T Yasuoka, A Matsumoto, I Abe, K AF Ishimaru, Y. Okada, S. Naito, H. Nagai, T. Yasuoka, A. Matsumoto, I. Abe, K. TI Two families of candidate taste receptors in fishes SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 Univ Tokyo, Tokyo, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A100 EP A100 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600355 ER PT J AU Li, CX Maier, SE Brasser, SM Waters, RS AF Li, C. X. Maier, S. E. Brasser, S. M. Waters, R. S. TI Early postnatal alcohol exposure reduced the size of the nucleus of the solitary tract (NST) in neonatal rat pups SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A34 EP A34 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600126 ER PT J AU Lopezjimenez, ND Cavenagh, MM Sainz, E Battey, JF Sullivan, SL AF Lopezjimenez, N. D. Cavenagh, M. M. Sainz, E. Battey, J. F. Sullivan, S. L. TI Identification of two putative taste signal transduction components SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 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 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A21 EP A21 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600080 ER PT J AU Sainz, E Cavenagh, MM Lopezjimenez, ND Battey, JF Northup, JK Sullivan, SL AF Sainz, E. Cavenagh, M. M. Lopezjimenez, N. D. Battey, J. F. Northup, J. K. Sullivan, S. L. TI Properties of the seven transmembrane core domains of the human T1RS SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD 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 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A104 EP A104 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600372 ER PT J AU Wang, H Zhou, M Rong, Q Inoue, M Bachmanov, AA Margolskee, RF Pfeifer, KE Huang, L AF Wang, H. Zhou, M. Rong, Q. Inoue, M. Bachmanov, A. A. Margolskee, R. F. Pfeifer, K. E. Huang, L. TI Expression of a voltage-gated potassium channel KCNQ1 in taste bud cells SO CHEMICAL SENSES LA English DT Meeting Abstract CT 28th Annual Meeting of the Association-for-Chemoreception-Sciences CY APR 26-30, 2006 CL Sarasota, FL SP Assoc Chemorecept Sci C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. NICHD, NIH, Bethesda, MD USA. Tokyo Univ Pharm & Life Sci, Tokyo, Japan. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD JUN PY 2006 VL 31 IS 5 BP A18 EP A18 PG 1 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 059VZ UT WOS:000238761600070 ER PT J AU Mabry, R Brasky, K Geiger, R Carrion, R Hubbard, GB Leppla, S Patterson, JL Georgiou, G Iverson, BL AF Mabry, R Brasky, K Geiger, R Carrion, R Hubbard, GB Leppla, S Patterson, JL Georgiou, G Iverson, BL TI Detection of anthrax toxin in the serum of animals infected with Bacillus anthracis by using engineered immunoassays SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROTECTIVE ANTIGEN; LETHAL FACTOR; EDEMA FACTORS; INHALATIONAL ANTHRAX; MONOCLONAL-ANTIBODY; PASSIVE PROTECTION; CELLULAR RECEPTOR; SMALL-MOLECULE; GUINEA-PIGS; BINDING AB Several strategies that target anthrax toxin are being developed as therapies for infection by Bacillus anthracis. Although the action of the tripartite anthrax toxin has been extensively studied in vitro, relatively little is known about the presence of toxins during an infection in vivo. We developed a series of sensitive sandwich enzyme-linked immunosorbent assays (ELISAs) for detection of both the protective antigen (PA) and lethal factor (LF) components of the anthrax exotoxin in serum. The assays utilize as capture agents an engineered high-affinity antibody to PA, a soluble form of the extracellular domain of the anthrax toxin receptor (ANTXR2/CMG2), or PA itself. Sandwich immunoassays were used to detect and quantify PA and LF in animals infected with the Ames or Vollum strains of anthrax spores. PA and LF were detected before and after signs of toxemia were observed, with increasing levels reported in the late stages of the infection. These results represent the detection of free PA and LF by ELISA in the systemic circulation of two animal models exposed to either of the two fully virulent strains of anthrax. Simple anthrax toxin detection ELISAs could prove useful in the evaluation of potential therapies and possibly as a clinical diagnostic to complement other strategies for the rapid identification of B. anthracis infection. C1 Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. SW Fdn Biomed Res, Dept Comparat Med, San Antonio, TX USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX USA. Natl Inst Allergy & Infect Dis, Bacterial Toxins & Therapeut Sect, Bethesda, MD USA. Univ Texas, Dept Chem Engn & Biomed Engn, Austin, TX USA. Univ Texas, Dept Chem & Biochem, Austin, TX 78712 USA. RP Iverson, BL (reprint author), Univ Texas, Inst Cellular & Mol Biol, 1 Univ Stn, Austin, TX 78712 USA. EM gg@che.utexas.edu; biverson@mail.utexas.edu FU NIAID NIH HHS [U01 AI56431, U01 AI056431] NR 48 TC 70 Z9 75 U1 0 U2 4 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 JUN PY 2006 VL 13 IS 6 BP 671 EP 677 DI 10.1128/CVI.00023-06 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 053WX UT WOS:000238337900011 PM 16760326 ER PT J AU Arlen, PM Pazdur, M Skarupa, L Rauckhorst, M Gulley, JL AF Arlen, Philip M. Pazdur, Mary Skarupa, Lisa Rauckhorst, Myrna Gulley, James L. TI A randomized phase II study of docetaxel alone or in combination with PANVAC (TM)-V (vaccinia) and PANVAC (TM)-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229) SO CLINICAL BREAST CANCER LA English DT Article DE chemotherapy; randomized trials; vaccine therapy ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN; COLORECTAL-CANCER; GAMMA-INTERFERON; CELL-LINES; EXPRESSION; 5-FLUOROURACIL; IMMUNOTHERAPY; CARCINOMA; ANTIBODY C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Arlen, PM (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 8B09, Bethesda, MD 20892 USA. EM pa52s@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 26 TC 28 Z9 29 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD JUN PY 2006 VL 7 IS 2 BP 176 EP 179 DI 10.3816/CBC.2006.n.032 PG 4 WC Oncology SC Oncology GA 112MP UT WOS:000242530400013 PM 16800982 ER PT J AU Warfel, NA Lepper, ER Zhang, CY Figg, WD Dennis, PA AF Warfel, NA Lepper, ER Zhang, CY Figg, WD Dennis, PA TI Importance of the stress kinase p38 alpha in mediating the direct cytotoxic effects of the thalidomide analogue, CPS49, in cancer cells and endothelial cells SO CLINICAL CANCER RESEARCH LA English DT Article ID RELAPSED MULTIPLE-MYELOMA; ACTIVATED PROTEIN-KINASE; PROSTATE-CANCER; LUNG-CANCER; P38; PATHWAY; ANGIOGENESIS; APOPTOSIS; THERAPY; CHEMOTHERAPY AB Purpose: Thalidomide has gained renewed interest as a cancer therapeutic due to its potential antiangiogenic effects. The thalidomide analogues CPS11 and CPS49 are active in preclinical angiogenesis assays and xenograft model systems, but the biochemical basis for these observations is unclear. Experimental Design: To address this question, we assessed the toxicity of these thalidomide analogues in cancer cells, endothelial cells, and genetically modified cells using assays that measure apoptotic and nonapoptotic cell death. Phosphospecific and native antibodies were used in immunoblotting and immunohistochemical experiments to assess the activation states of kinases that control cellular survival in vitro and in vivo. Results: CPS49 predominantly induced nonapoptotic cell death in lung cancer cells, prostate cancer cells, and endothelial cells in a dose-dependent manner, whereas CPS11 was not cytotoxic. CPS49 did not inhibit kinases that promote survival, such as Akt or extracellular signal-regulated kinase, but rather rapidly activated the stress kinase p38 pathway in both cancer cells and endothelial cells. CPS49 activated p38 in tumor xenografts. Using p38 alpha-/- cells or an inhibitor of p38, we show that the presence and activation of p38(x is important for cytotoxicity in all cell types examined. Conclusions: Our studies identify a unifying mechanism of action for cytotoxicity of the tetraflourinated thalidomide analogue, CPS49, and suggest that activation of p38 could serve as a biomarker in clinical trials with CPS49. C1 NCI, Navy Med Oncol, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Clin Pharmacol Res Core, Sci Applicat Int Corp Frederick Inc, Frederick, MD USA. RP Dennis, PA (reprint author), NCI, Navy Med Oncol, Med Oncol Branch, Ctr Canc Res, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 25 TC 12 Z9 12 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 JUN 1 PY 2006 VL 12 IS 11 BP 3502 EP 3509 DI 10.1158/1078-0432.CCR-05-1837 PN 1 PG 8 WC Oncology SC Oncology GA 051OG UT WOS:000238169800037 PM 16740776 ER PT J AU Compton, C AF Compton, C TI The Cancer and Leukemia Group B Pathology Committee at 50 SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; POSITIVE BREAST-CANCER; NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOCYTIC-LEUKEMIA; PHASE-II; PROMOTER HYPERMETHYLATION; MICROSATELLITE INSTABILITY; INTENSIVE CHEMOTHERAPY; MONOCLONAL-ANTIBODIES; COLORECTAL CANCERS AB The Pathology Committee of the Cancer and Leukemia Group B (CALGB) is broadly and deeply integrated into the multidisciplinary clinical and scientific operations of the group. It has five major functions in CALGB. First, it insure the highest possible quality of pathologic data in tissue based correlative science studies through comprehensive quality control of all tissues collected banked, and distributed to investigators and of all morphology-based studies done within the CALAB. Within this context, the Pathology Committee has the goal of eliminating to the greatest degree possible, variation in methodology, interpretation and reporting of pathologic data that would compromise reproducibility of correlative science results and to assure accuracy uniformity and completeness of the pathologic data. Second, the committee provides expert pathologic consultation in the development of clinical trials and correlative science studies that involve pathologic issues and/or materials. Third it provides high-quality tissue banking and centralized morphology-based technical support services (e.g. histologic sections for immunohistochemistry, tissue microarrays, etc.) for all CALGB investigators. Fourth, it initiates and executes high-quality pathologic research using CALGB and intergroup resources. Lastly, it provides group-wide education on pathology-related issues relevant to trial design, scientific study design, and specimen banking. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Compton, C (reprint author), NCI, NIH, Room 10A52,31 Ctr Dr,MSC 2580, Bethesda, MD 20892 USA. EM comptcar@mail.nih.gov NR 58 TC 3 Z9 3 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 JUN 1 PY 2006 VL 12 IS 11 SU S BP 3617S EP 3621S DI 10.1158/1078-0432.CCR-06-9009 PN 2 PG 5 WC Oncology SC Oncology GA 052IR UT WOS:000238227900012 PM 16740795 ER PT J AU Sampson, ML Eberhardt, JS Remaley, AT AF Sampson, M. L. Eberhardt, J. S. Remaley, A. T. TI Bayesian delta error value: A new metric for near real-time error detection. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Clinical-Chemistry CY JUL 23-27, 2006 CL Chicago, IL SP Amer Assoc Clin Chem C1 NIH, Bethesda, MD 20892 USA. DecisionQ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2006 VL 52 IS 6 SU S MA A19 BP A7 EP A8 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 048CT UT WOS:000237925900020 ER PT J AU Stickle, DF Seligman, ML Landmark, JD Quon, MJ AF Stickle, D. F. Seligman, M. L. Landmark, J. D. Quon, M. J. TI Predicted effects of assay precision on a population distribution of delta values for serial measurements of hemoglobin A1c SO CLINICAL CHEMISTRY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-of-Clinical-Chemistry CY JUL 23-27, 2006 CL Chicago, IL SP Amer Assoc Clin Chem C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Univ Washington, Seattle, WA 98195 USA. Natl Inst Hlth, Bethesda, MD USA. RI Quon, Michael/B-1970-2008; Stickle, Douglas/A-9682-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 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 JUN PY 2006 VL 52 IS 6 SU S MA C66 BP A99 EP A100 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 048CT UT WOS:000237925900308 ER PT J AU Aoki, CA Dawson, K Kenny, TP Gershwin, ME Bowlus, CL AF Aoki, Christopher A. Dawson, Kevin Kenny, Thomas P. Gershwin, M. Eric Bowlus, Christopher L. TI Gene expression by PBMC in primary sclerosing cholangitis: Evidence for dysregulation of immune mediated genes SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article DE microarray; TNF-alpha induced protein 6 (TNFaip6); membrane-spanning 4-domains subfamily A (ms4a); similar to mothers against decapentaplegic homolog 5 (SMAD 5) ID INTERLEUKIN-2 RECEPTOR-BETA; HYALURONAN-BINDING PROTEIN; INTER-ALPHA-INHIBITOR; AFFINITY IGE RECEPTOR; LYMPHOCYTE-B; TSG-6; FAMILY; IDENTIFICATION; ACTIVATION; CLONING AB Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA ( mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-alpha induced protein 6 (TNFaip6) and membrane-spanning 4-domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immunemediated. C1 Univ Calif Davis, Div Gastroenterol, Sacramento, CA 95817 USA. Univ Calif Davis, NIH, Natl Ctr Excellence Nutr Genom, Davis, CA 95616 USA. Univ Calif Davis, NIH, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. RP Bowlus, CL (reprint author), Univ Calif Davis, Div Gastroenterol, 4150 V St,PSSB 3500, Sacramento, CA 95817 USA. EM clbowlus@ucdavis.edu RI Bowlus, Christopher/N-9276-2016 OI Bowlus, Christopher/0000-0002-3906-6811 NR 39 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PD JUN-DEC PY 2006 VL 13 IS 2-4 BP 265 EP 271 DI 10.1080/17402520600800085 PG 7 WC Immunology SC Immunology GA 120ZP UT WOS:000243126000017 PM 17162367 ER PT J AU Krishnan, K Bruce, B Hewitt, S Thomas, D Khanna, C Helman, LJ AF Krishnan, Kartik Bruce, Ben Hewitt, Stephen Thomas, Dafydd Khanna, Chand Helman, Lee J. TI Ezrin mediates growth and survival in Ewing's sarcoma through the AKT/mTOR, but not the MAPK, signaling pathway SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ezrin; Ewing's sarcoma; AKT; immunohistochemistry ID PROTEIN-KINASE-B; ERM PROTEINS; PLASMA-MEMBRANE; CELL-SURVIVAL; LINKER EZRIN; PHOSPHORYLATION; CYTOSKELETON; ASSOCIATION; ACTIVATION; EXPRESSION AB Recent reports on the role of the membrane-cytoskeleton linker protein ezrin in sarcomas showed an effect on the formation of metastases, dependent on the level of ezrin expression. In this study, we explore the role of ezrin in Ewing's sarcoma, a frequently fatal mesenchymal neoplasm of children and young adults. Through both immunohistochemistry and Western immunoblot studies we find ubiquitous, high-level expression of ezrin in Ewing's sarcoma. In contrast to the observations in osteosarcoma and rhabdomyosarcoma, we demonstrate that inhibition of ezrin-mediated signal transduction, through the expression of a non-phosphorylatable T567A mutant, slows primary growth of Ewing's sarcoma cells in vitro. This reduction in growth is a result of increased apoptosis in the mutant expressing cells. We further show that expression of this mutant reduces the ability of Ewing's sarcoma cells to form experimental metastases in vivo. Molecular examination reveals that the action of ezrin in Ewing's sarcoma is dependent on the AKT/mTOR signal transduction cascade, but not MAP Kinase. These results, therefore, demonstrate that, in Ewing's sarcoma, the biology of ezrin is distinct from that described in other sarcomas. This study further validates ezrin as a potential therapeutic target. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Metastasis & Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bldg 31,Room 3A11,31 Ctr Dr, Bethesda, MD 20892 USA. EM helmanl@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 NR 35 TC 47 Z9 58 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JUN PY 2006 VL 23 IS 3-4 BP 227 EP 236 DI 10.1007/s10585-006-9033-y PG 10 WC Oncology SC Oncology GA 101NX UT WOS:000241748600008 PM 17028919 ER PT J AU Lattouf, JB Arlen, PM Pinto, PA Gulley, JL AF Lattouf, Jean-Baptiste Arlen, Philip M. Pinto, Peter A. Gulley, James L. TI A phase I feasibility study of an intraprostatic prostate-specific antigen-based vaccine in patients with prostate cancer with local failure after radiation therapy or clinical progression on androgen-deprivation therapy in the absence of local definitive therapy SO CLINICAL GENITOURINARY CANCER LA English DT Article DE clinical trials; epitopes; granulocyte-macrophage colony-stimulating factor; TRICOM ID ANTITUMOR RESPONSES; DIVERSIFIED PRIME; ONCOLOGY-GROUP; VIRUS; RADIOTHERAPY; TRIAL; SURVIVAL; PSA C1 NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Clin, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Canc Res Ctr, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,8B09,MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 22 TC 2 Z9 2 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1558-7673 J9 CLIN GENITOURIN CANC JI Clin. Genitourin. Cancer PD JUN PY 2006 VL 5 IS 1 BP 89 EP 92 DI 10.3816/CGC.2006.n.024 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 112LI UT WOS:000242527000013 PM 16859586 ER PT J AU Hallett, M AF Hallett, M TI What's up? SO CLINICAL NEUROPHYSIOLOGY LA English DT Editorial Material ID EVOKED VESTIBULOCOLLIC REFLEXES; POLARITY; CLICK C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, 10-5N226,10 Ctr Dr MDS 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov OI Hallett, Mark/0000-0002-3180-6811 NR 7 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2006 VL 117 IS 6 BP 1167 EP 1168 DI 10.1016/j.clinph.2006.03.013 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 059IH UT WOS:000238726000001 PM 16677858 ER PT J AU Stubblefield, MD Slovin, S MacGregor-Cortelli, B Muzzy, J Scher, H Wright, J Esseltine, D Schenkein, D O'Connor, OA AF Stubblefield, MD Slovin, S MacGregor-Cortelli, B Muzzy, J Scher, H Wright, J Esseltine, D Schenkein, D O'Connor, OA TI An electrodiagnostic evaluation of the effect of pre-existing peripheral nervous system disorders in patients treated with the novel proteasome inhibitor bortezomib SO CLINICAL ONCOLOGY LA English DT Article DE bortezomib; electrodiagnosis; lymphoma; neuropathy; prostate cancer; radiculopathy ID NEUROLOGIC COMPLICATIONS; CMAP AMPLITUDE; NEUROPATHY; NEUROTOXICITY; CANCER; TAXOL AB Aims: Bortezomib (Velcade(R)), a novel proteasome inhibitor, has shown promise in the treatment of malignancies, including multiple myeloma and non-Hodgkin's lymphoma. Several studies have identified neuropathy as a potentially dose-limiting side effect of treatment with bortezomib. We report the clinical and electrodiagnostic data from four patients who developed signs and symptoms of peripheral neuropathy from treatment with bortezomib. Materials and methods: Patients were included if they were enrolled in active phase 2 trials of bortezomib for non-Hodgkin's lymphoma or prostate cancer, developed signs and symptoms of peripheral neuropathy, and were referred for electrodiagnostic evaluation. Results: Four patients, including two with non-Hodgkin's lymphoma and two with prostate cancer, underwent electrodiagnostic testing. Electrodiagnostic evaluation showed pre-existing peripheral nervous system disorders in three out of four patients. Multiple peripheral nervous system disorders were present in two out of four patients. Conclusions: Bortezomib can cause a predominately sensory axonal polyneuropathy. Pre-existing peripheral nervous system disorders, such as neuropathy and radiculopathy, are common in patients with cancer, and may pre-dispose to the development of symptomatic neuronal toxicity when treated with bortezomib. Baseline electrodiagnostic evaluation may identify patients with pre-existing peripheral nervous system disorders at risk for additive neuronal toxicity from neurotoxic chemotherapeutic agents. C1 Mem Sloan Kettering Canc Ctr, Rehabil Med Serv, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Lymphoma Serv, New York, NY 10021 USA. NCI, Drug Dev Branch, Bethesda, MD 20892 USA. Millennium Pharmaceut, Cambridge, MA USA. Mem Sloan Kettering Canc Ctr, Dev Chemotherapy Serv, New York, NY 10021 USA. RP Stubblefield, MD (reprint author), Mem Sloan Kettering Canc Ctr, Rehabil Med Serv, Dept Neurol, Box 349,1275 York Ave, New York, NY 10021 USA. EM stubblem@mskcc.org FU NCI NIH HHS [U01 CA 69913] NR 23 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0936-6555 J9 CLIN ONCOL-UK JI Clin. Oncol. PD JUN PY 2006 VL 18 IS 5 BP 410 EP 418 DI 10.1016/j.clon.2005.12.008 PG 9 WC Oncology SC Oncology GA 049AV UT WOS:000237988700008 PM 16817333 ER PT J AU Marty, AM Jahrling, PB Gelsbert, TW AF Marty, Aileen M. Jahrling, Peter B. Gelsbert, Thomas W. TI Viral hemorrhagic fevers SO CLINICS IN LABORATORY MEDICINE LA English DT Review ID RIFT-VALLEY FEVER; HANTAVIRUS PULMONARY SYNDROME; EBOLA-VIRUS-INFECTION; NECROSIS-FACTOR-ALPHA; DISSEMINATED INTRAVASCULAR COAGULATION; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; NONSTRUCTURAL PROTEINS NS2A; REVERSE TRANSCRIPTION-PCR; POLYMERASE-CHAIN-REACTION; NEW-WORLD ARENAVIRUSES AB A taxonomically diverse set of single-stranded ribonucleic acid (ssRNA) viruses from four diverse viral families Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae cause an acute systemic febrile syndrome called viral hemorrhagic fever (VHF). The syndrome produces combinations of prostration, malaise, increased vascular permeability, and coagulation maladies. In severe illness, VHF may include generalized bleeding but the bleeding does not typically constitute a life-threatening loss of blood volume. To a certain extent, it is a sign of damage to the vascular endothelium and is an indicator of disease severity in specific target organs. Although the viruses that cause hemorrhagic fever W) can productively replicate in endothelial cells, much of the disease pathology including impairment to the vascular system is thought to result primarily from the release of a variety of mediators from virus-infected cells, such as monocytes and macrophages that subsequently alter vascular function and trigger the coagulation disorders that epitomize these infections. While significant progress has been made over the last several years in dissecting out the molecular biology and pathogenesis of the HF viruses, there are currently no vaccines or drugs licensed available for most of the VHFs. C1 Battelle Mem Inst, Arlington, VA 22202 USA. NIAID, Integrated Res Facil, NIH, Bethesda, MD 20817 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Marty, AM (reprint author), Battelle Mem Inst, Suite 601,1550 Crystal Dr, Arlington, VA 22202 USA. EM martya@battelle.org NR 321 TC 42 Z9 45 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 EI 1557-9832 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 2006 VL 26 IS 2 BP 345 EP + DI 10.1016/j.cll.2006.05.001 PG 44 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 075GH UT WOS:000239871800006 PM 16815457 ER PT J AU Raju, TNK AF Raju, Tonse N. K. TI Historical perspectives on the etiology of cerebral palsy SO CLINICS IN PERINATOLOGY LA English DT Article AB This essay presents the early history on the evolution of concepts about the etiology of cerebral palsy, especially the contributions of the early pioneers. Insight into how they derived their hypotheses, including the errors they made, can help one understand the complex processes of deciphering etiologic associations. C1 NICHHD, Pregnancy & Perinatol Branch, CDBPM, NIH, Bethesda, MD 20892 USA. RP Raju, TNK (reprint author), NICHHD, Pregnancy & Perinatol Branch, CDBPM, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov NR 37 TC 6 Z9 11 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD JUN PY 2006 VL 33 IS 2 BP 233 EP + DI 10.1016/j.clp.2006.03.006 PG 19 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 062PI UT WOS:000238956600002 PM 16765722 ER PT J AU Knight, DC Nguyen, HT Bandettini, PA AF Knight, David C. Nguyen, Hanh T. Bandettini, Peter A. TI The role of awareness in delay and trace fear conditioning in humans SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article ID SKIN-CONDUCTANCE RESPONSES; BRAIN SYSTEMS; COGNITIVE NEUROSCIENCE; NONDECLARATIVE MEMORY; EYEBLINK RESPONSE; PREFRONTAL CORTEX; HUMAN AMYGDALA; ACQUISITION; RABBITS; EXPRESSION AB Expression of conditional fear without awareness has been previously demonstrated during delay conditioning, a procedure in which the conditioned stimulus (CS) and unconditioned stimulus (UCS) overlap. However, less is known about the role of awareness in trace fear conditioning, where an inter val of time separates the CS and UCS. The present study assessed skin conductance response (SCR) and UCS expectancy during delay and trace conditioning. UCS predictability was varied on a trial-by-trial basis by presenting perithreshold auditory CSs. Differential UCS expectancies were demonstrated only on perceived delay and trace trials. Learning-related SCRs were observed during both perceived and unperceived delay CSs. In contrast, differential SCRs were demonstrated only for perceived trace CSs. These data suggest that awareness is necessary for conditional responding during trace, but not delay, fear conditioning. C1 NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Knight, DC (reprint author), NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Room 1D80, Bethesda, MD 20892 USA. EM knightd@mail.nih.gov FU Intramural NIH HHS NR 40 TC 42 Z9 42 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD JUN PY 2006 VL 6 IS 2 BP 157 EP 162 DI 10.3758/CABN.6.2.157 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 084EW UT WOS:000240516000007 PM 17007236 ER PT J AU Ballatori, N Henson, JH Seward, DJ Cai, SY Runnegar, M Fricker, G Miller, DS Boyer, JL AF Ballatori, N Henson, JH Seward, DJ Cai, SY Runnegar, M Fricker, G Miller, DS Boyer, JL TI Retention of structural and functional polarity in cultured skate hepatocytes undergoing in vitro morphogenesis SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE polarized hepatocyte culture model; bile secretion; membrane transport; Bsep; Mrp2; Oatp; ATP; glutathione ID SALT EXPORT PUMP; RAT HEPATOCYTES; RAJA-ERINACEA; EXTRACELLULAR-MATRIX; FISH HEPATOCYTES; MULTIDRUG RESISTANCE; TAURINE CHANNEL; BILE-SALTS; EXPRESSION; MODEL AB The present study characterized a primary culture model of hepatocytes isolated from the little skate, Leucoraja erinacea, that maintain remarkable structural and functional polarity over 7 days in culture. Skate hepatocytes were isolated as clusters of 3-20 hepatocytes surrounding a bile canaliculus, rather than as single cells. Trypan blue and propidium iodide exclusion was found to be > 98%, and the cells maintained high intracellular concentrations of K+, ATP, and reduced glutathione (GSH), and high ratios of ATP/AD]P and GSH/GSSG. Glutathione S-transferase activity remained constant, whereas cytochrome P450 activity declined to 16% of initial levels after 7 days. Quantitative RT-PCR analysis revealed that the mRNA levels of several genes remained constant over the 7-day period, whereas Bsep, the canalicular bile salt export pump, levels declined slowly to 30% of initial values. In the presence of dexamethasone, the cells underwent a morphogenesis in which the clusters reannealed into a three-dimensional network of chords. During this morphogenesis, skate hepatocytes clusters maintained a polarized distribution of actin filaments and microtubules, as well as apical and basolateral membrane domains. Polarity of membrane transport systems was confirmed both morphologically, using antibodies raised against Bsep and Mrp2, the canalicular multispecific organic anion transporter, and functionally, by monitoring secretion of the fluorescent organic anions NBD-taurocholate, a Bsep substrate, and fluorescein-methotrexate, an Mrp2 substrate, into the bile canalicular spaces. Overall, the results indicate that in contrast with mammalian hepatocytes, isolated skate hepatocyte clusters retain polarity in culture, and provide an excellent system for investigating long-term effects of drugs and xenobiotics on hepatobiliary functions, and for studying in vitro morphogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY 14642 USA. Dickinson Coll, Dept Biol, Carlisle, PA 17013 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ctr Liver, New Haven, CT 06520 USA. Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. Inst Pharmazeut Technol & Biopharm, D-69120 Heidelberg, Germany. NIEHS, Cellular & Mol Pharmacol Lab, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Ballatori, N (reprint author), Univ Rochester, Sch Med, Dept Environm Med, Box EHSC, Rochester, NY 14642 USA. EM Ned_Ballatori@urmc.rochester.edu FU NIDDK NIH HHS [DK48823, DK34989, DK25636]; NIEHS NIH HHS [ES03828, ES06484, ES07026] NR 46 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JUN PY 2006 VL 144 IS 2 BP 167 EP 179 DI 10.1016/j.cbpb.2006.02.005 PG 13 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 051SE UT WOS:000238180300004 PM 16567119 ER PT J AU DeKosky, ST Fitzpatrick, A Ives, DG Saxton, J Williamson, J Lopez, OL Burke, G Fried, L Kuller, LH Robbins, J Tracy, R Woolard, N Dunn, L Kronmal, R Nahin, R Furberg, C AF DeKosky, ST Fitzpatrick, A Ives, DG Saxton, J Williamson, J Lopez, OL Burke, G Fried, L Kuller, LH Robbins, J Tracy, R Woolard, N Dunn, L Kronmal, R Nahin, R Furberg, C CA GEMS Investigators TI The Ginkgo Evaluation of Memory (GEM) study: Design and baseline data of a randomized trial of Ginkgo biloba extract in prevention of dementia SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Ginkgo biloha; dementia; Alzheimer's disease; primary prevention trial ID MILD COGNITIVE IMPAIRMENT; PROBABLE ALZHEIMERS-DISEASE; ACUTE ISOBARIC HYPOXIA; LAST 2 DECADES; CARDIOVASCULAR HEALTH; RAT HEARTS; EGB 761; TERPENOID CONSTITUENTS; OXIDATIVE STRESS; OLD RATS AB The epidemic of late life dementia, prominence of use of alternative medications and supplements, and initiation of efforts to determine how to prevent dementia have led to efforts to conduct studies aimed at prevention of dementia. The GEM (Ginkgo Evaluation of Memory) study was initially designed as a 5-year, randomized double-blind, placebo-controlled trial of Ginkgo biloba, administered in a dose of 120 mg twice per day as EGb761, in the prevention of dementia (and especially Alzheimer's disease) in normal elderly or those with mild cognitive impairment. The study anticipates 8.5 years of participant follow-up. Initial power calculations based on estimates of incidence rates of dementia in the target population (age 75+) led to a 3000-person study, which was successfully recruited at four clinical sites around the United States from September 2000 to June 2002. Primary outcome is incidence of all-cause dementia; secondary outcomes include rate of cognitive and functional decline, the incidence of cardiovascular and cerebrovascular events, and mortality. Following screening to exclude participants with incident dementia at baseline, an extensive neuropsychological assessment was performed and participants were randomly assigned to treatment groups. All participants are required to have a proxy who agreed to provide an independent assessment of the functional and cognitive abilities of the participant. Assessments are repeated every 6 months. Significant decline at any visit, defined by specific changes in cognitive screening scores, leads to a repeat detailed neuropsychological battery, neurological and medical evaluation and MRI scan of the brain. The final diagnosis of dementia is achieved by a consensus panel of experts. Side effects and adverse events are tracked by computer at the central data coordinating center and unblinded data are reviewed by an independent safety monitoring board. Studies such as these are necessary for this and a variety of other potential protective agents to evaluate their effectiveness in preventing or slowing the emergence of dementia in the elderly population. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Calif Davis, Sacramento, CA 95817 USA. Univ Vermont, Colchester, Essex, England. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. RP DeKosky, ST (reprint author), Univ Pittsburgh, Dept Neurol, 3471 5th Ave,Suite 811, Pittsburgh, PA 15213 USA. EM DeKoskyST@upmc.edu OI Nahin, Richard/0000-0002-3682-4816 FU NCCIH NIH HHS [U01 AT000162] NR 56 TC 97 Z9 106 U1 0 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 JUN PY 2006 VL 27 IS 3 BP 238 EP 253 DI 10.1016/j.cct.2006.02.007 PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 046DP UT WOS:000237791900004 PM 16627007 ER PT J AU DePamphilis, ML Blow, JJ Ghosh, S Saha, T Noguchi, K Vassilev, A AF DePamphilis, ML Blow, JJ Ghosh, S Saha, T Noguchi, K Vassilev, A TI Regulating the licensing of DNA replication origins in metazoa SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID XENOPUS EGG EXTRACTS; RECOGNITION COMPLEX PROTEIN-1; CYCLE-DEPENDENT REGULATION; CELL-CYCLE; S-PHASE; RE-REPLICATION; CDK PHOSPHORYLATION; CHROMATIN ASSOCIATION; ATP-HYDROLYSIS; NUCLEAR IMPORT AB Eukaryotic DNA replication is a highly conserved process; the proteins and sequence of events that replicate animal genomes are remarkably similar to those that replicate yeast genomes. Moreover, the assembly of prereplication complexes at DNA replication origins ('DNA licensing') is regulated in all eukaryotes so that no origin fires more than once in a single cell cycle. And yet there are significant differences between species both in the selection of replication origins and in the way in which these origins are licensed to operate. Moreover, these differences impart advantages to multicellular animals and plants that facilitate their development, such as better control over endoreduplication, flexibility in origin selection, and discrimination between quiescent and proliferative states. C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Dundee, Wellcome Trust Bioctr, Dundee DD1 5EH, Scotland. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6-3A-15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov RI Blow, J. Julian/B-3977-2009 OI Blow, J. Julian/0000-0002-9524-5849 FU Cancer Research UK [A3135] NR 74 TC 117 Z9 119 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2006 VL 18 IS 3 BP 231 EP 239 DI 10.1016/j.ceb.2006.04.001 PG 9 WC Cell Biology SC Cell Biology GA 051GM UT WOS:000238149600002 PM 16650748 ER PT J AU Gorski, SA Dundr, M Misteli, T AF Gorski, SA Dundr, M Misteli, T TI The road much traveled: trafficking in the cell nucleus SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID LIVING HUMAN-CELLS; FLUORESCENCE CORRELATION SPECTROSCOPY; MESSENGER-RNA; IN-VIVO; MAMMALIAN-CELLS; MACROMOLECULAR MOBILITY; BINDING-PROTEINS; GENE-EXPRESSION; RAPID EXCHANGE; HISTONE H1 AB Trafficking of RNA molecules and proteins within the cell nucleus is central to genome function. Recent work has revealed the nature of RNA and protein motion within the nucleus and across the nuclear membrane. These studies have given insight into how molecules find their destinations within the nucleus and have uncovered some of the structural properties of the nuclear microenvironment. Control of RNA and protein trafficking is now emerging as a physiological regulatory mechanism in gene expression and nuclear function. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 61 TC 70 Z9 72 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 2006 VL 18 IS 3 BP 284 EP 290 DI 10.1016/j.ceb.2006.03.002 PG 7 WC Cell Biology SC Cell Biology GA 051GM UT WOS:000238149600009 PM 16621498 ER PT J AU Sen, R Oltz, E AF Sen, R Oltz, E TI Genetic and epigenetic regulation of IgH gene assembly SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HEAVY-CHAIN GENE; RAG2 C-TERMINUS; B-CELL; V(D)J RECOMBINATION; HISTONE ACETYLATION; FEEDBACK INHIBITION; ALLELIC EXCLUSION; INTRONIC ENHANCER; DJ REARRANGEMENT; TRANSGENIC MICE AB Precursor B cells assemble a diverse repertoire of immunoglobulin (Ig) genes by the process of V(D)J recombination. Assembly of IgH genes is regulated in a tissue- and stage-specific manner via the activation and then the inactivation of distinct regions within the one megabase IgH locus. Recent studies have shown that regional control is achieved using a combination of genetic and epigenetic strategies, which modulate chromatin accessibility to V(D)J recombinase, relocate IgH loci within the nucleus, and promote changes in locus conformation that alter the spatial proximity of target gene segments. Orchestration of these regulatory processes is crucial for the generation of a functional B cell repertoire. C1 Vanderbilt Univ, Dept Microbiol & Immunol, Coll Med, Nashville, TN 37206 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Oltz, E (reprint author), Vanderbilt Univ, Dept Microbiol & Immunol, Coll Med, A4203 MCN,1161 21st Ave S, Nashville, TN 37206 USA. EM eugene.oltz@vanderbilt.edu FU Intramural NIH HHS NR 42 TC 27 Z9 27 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2006 VL 18 IS 3 BP 237 EP 242 DI 10.1016/j.coi.2006.03.008 PG 6 WC Immunology SC Immunology GA 045IL UT WOS:000237735700002 PM 16616470 ER PT J AU Martomo, SA Gearhart, PJ AF Martomo, SA Gearhart, PJ TI Somatic hypermutation: subverted DNA repair SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN GENE DIVERSIFICATION; INDUCED CYTIDINE DEAMINASE; POLYMERASE-ETA; MISMATCH REPAIR; ANTIBODY DIVERSIFICATION; IG HYPERMUTATION; CUTTING EDGE; B-CELLS; MICE AB Somatic hypermutation generates high-affinity antibodies of different isotypes that efficiently protect us against a plethora of pathogens. Recent analyses of the types of mutations produced in gene-deficient mice have indicated how DNA repair proteins are drawn into the pathway. Activation-induced cytosine deaminase begins the process by deaminating cytosine to uracil in DNA. The uracils are then recognized by the base excision repair protein uracil DNA glycosylase and by the mismatch repair proteins MutS homologue 2 and MutS homologue 6. Instead of repairing the uracils, these proteins attract low fidelity DNA polymerases, which synthesize nucleotide substitutions at an unprecedented level. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov FU Intramural NIH HHS NR 50 TC 25 Z9 25 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2006 VL 18 IS 3 BP 243 EP 248 DI 10.1016/j.coi.2006.03.007 PG 6 WC Immunology SC Immunology GA 045IL UT WOS:000237735700003 PM 16616477 ER PT J AU Hinrichs, CS Gattinoni, L Restifo, NP AF Hinrichs, Christian S. Gattinoni, Luca Restifo, Nicholas P. TI Programming CD8(+) T cells for effective immunotherapy SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID IN-VIVO PERSISTENCE; VERSUS-HOST-DISEASE; CENTRAL-MEMORY; TRANSFER THERAPY; METASTATIC MELANOMA; STEM-CELLS; HISTONE ACETYLATION; LINEAGE COMMITMENT; CUTTING EDGE; DIFFERENTIATION AB The differentiation state of CD8(+) T cells has emerged as a crucial determinant of their ability to respond to tumor and infection. Signals from T-cell receptors, co-stimulatory molecules and cytokine receptors direct the differentiation process. These signals 'program' sustained and heritable gene expression patterns that govern progressive differentiation and lineage commitment. The epigenetic mechanisms by which T cells are programmed are just beginning to be elucidated. Understanding the mechanisms that control CD8(+) T-cell differentiation is important in the development of novel immunotherapy strategies. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 71 TC 46 Z9 46 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 2006 VL 18 IS 3 BP 363 EP 370 DI 10.1016/j.coi.2006.03.009 PG 8 WC Immunology SC Immunology GA 045IL UT WOS:000237735700021 PM 16616471 ER PT J AU Aravind, L Iyer, LM Koonin, EV AF Aravind, L. Iyer, Lakshminarayan M. Koonin, Eugene V. TI Comparative genomics and structural biology of the molecular innovations of eukaryotes SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID NUCLEAR-PORE-COMPLEX; COATED VESICLES; EVOLUTION; ORIGIN; PROTEIN; DOMAIN; BACTERIAL; YEAST; CELL; DNA AB Eukaryotes encode numerous proteins that either have no detectable homologs in prokaryotes or have only distant homologs. These molecular innovations of eukaryotes may be classified into three categories: proteins and domains inherited from prokaryotic precursors without drastic changes in biochemical function, but often recruited for novel roles in eukaryotes; new superfamilies or distinct biochemical functions emerging within pre-existing protein folds; and domains with genuinely new folds, apparently 'invented' at the outset of eukaryotic evolution. Most new folds emerging in eukaryotes are either a-helical or stabilized by metal chelation. Comparative genomics analyses point to an early phase of rapid evolution, and dramatic changes between the origin of the eukaryotic cell and the advent of the last common ancestor of extant eukaryotes. Extensive duplication of numerous genes, with subsequent functional diversification, is a distinctive feature of this turbulent era. Evolutionary analysis of ancient eukaryotic proteins is generally compatible with a two-symbiont scenario for eukaryotic origin, involving an alpha-proteobacterium (the ancestor of the mitochondria) and an archaeon, as well as key contributions from their selfish elements. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov; ekoonin@mail.nih.gov FU Intramural NIH HHS NR 61 TC 66 Z9 67 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2006 VL 16 IS 3 BP 409 EP 419 DI 10.1016/j.sbi.2006.04.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064IJ UT WOS:000239082100019 PM 16679012 ER PT J AU Xiang, ZX AF Xiang, ZX TI Advances in homology protein structure modeling SO CURRENT PROTEIN & PEPTIDE SCIENCE LA English DT Review DE homology modeling; structure refinement; sequence alignment; side-chain prediction; loop prediction; model assessment; colony energy; conformation sampling; structural genomics ID HIDDEN MARKOV-MODELS; SIDE-CHAIN PREDICTION; CONFORMATIONAL FREE-ENERGIES; AB-INITIO PREDICTIONS; FOLD-RECOGNITION; SEQUENCE ALIGNMENT; PROFILE ALIGNMENT; LOOP PREDICTION; MOLECULAR-MECHANICS; TERTIARY STRUCTURE AB Homology modeling plays a central role in determining protein structure in the structural genomics project. The importance of homology modeling has been steadily increasing because of the large gap that exists between the overwhelming number of available protein sequences and experimentally solved protein structures, and also, more importantly, because of the increasing reliability and accuracy of the method. In fact., a protein sequence with over 30% identity to a known structure can often be predicted with an accuracy equivalent to a low-resolution X-ray structure. The recent advances in homology modeling, especially in detecting distant homologues, aligning sequences with template structures, modeling of loops and side chains, as well as detecting errors in a model, have contributed to reliable prediction of protein structure, which was not possible even several years ago. The ongoing efforts in solving protein structures, which can be time-consuming and often difficult, will continue to spur the development of a host of new computational methods that can fill in the gap and further contribute to understanding the relationship between protein structure and function. C1 Natl Inst Hlth, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Xiang, ZX (reprint author), Natl Inst Hlth, Ctr Mol Modeling, Ctr Informat Technol, Bldg 12A,Room 2051,12 S Dr, Bethesda, MD 20892 USA. EM xiangz@mail.nih.gov FU CIT NIH HHS [Z01 CT000265-09] NR 137 TC 112 Z9 121 U1 4 U2 27 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2037 J9 CURR PROTEIN PEPT SC JI Curr. Protein Pept. Sci. PD JUN PY 2006 VL 7 IS 3 BP 217 EP 227 DI 10.2174/138920306777452312 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 052RM UT WOS:000238251100004 PM 16787261 ER PT J AU Wu, XL Simone, J Hewgill, D Siegel, R Lipsky, PE He, LS AF Wu, XL Simone, J Hewgill, D Siegel, R Lipsky, PE He, LS TI Measurement of two caspase activities simultaneously in living cells by a novel dual FRET fluorescent indicator probe SO CYTOMETRY PART A LA English DT Article DE caspase substrate; fluorescence resonance energy transfer (FRET); cyan fluorescent protein; yellow fluorescent protein; monomeric red fluorescent protein; flow cytometry ID RESONANCE ENERGY-TRANSFER; FLUOROCHROME-LABELED INHIBITORS; NECROSIS-FACTOR RECEPTOR; INDUCED APOPTOSIS; HELA-CELLS; REAL-TIME; MEASURING DYNAMICS; DNA FRAGMENTATION; IN-VIVO; ACTIVATION AB Background: A number of fluorescent caspase substrates and FRET-based indicators have been developed to study the in vivo activation of caspases, a conserved family of proteases critical in inflammatory, and apoptosis signaling pathways. To date, all substrates have measured only one caspase activity. Here, we describe a FRET-based probe for simultaneously measuring two distinct caspase activities in living cells. Methods: This probe consists of a CFP-YFP-mRFP fusion protein containing a caspase-3-cleavage motif, DEVD, between CFP and YFP and a caspase-6-cleavage site, VEID, between YFP and mRFP. DEVDase and VEIDase activities could be assessed simultaneously by monitoring din-finished FRET mediated by cleavage of either or both of these protease cleavage sites using flow cytometry. Results: DEVDase and VEIDase activities were completely inhibited by the pan-caspase inhibitor z-VAD-fmk and enhanced by DNA-damaging drugs or by anti-Fas stimulation. DEVD and VEID cleavage specificities were validated by using caspase-3-deficient MCF7-Fas cells and a caspase-6-specific inhibitor. Kinetic analysis with the FRET probe revealed that caspase-3 activation consistently, preceded caspase-6 by similar to 30 mill following induction of apoptosis. Conclusions: We have developed a novel FRET-based probe for simultaneous detection of two caspase activities in living cells Using flow cytometry. Simultaneous detection of two caspase activities using this probe has clearly provided information of the ordering of caspase-3 and -6 in the apoptotic pathway. (c) 2006 International Society for Analytical Cytology. C1 NIAMSD, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP He, LS (reprint author), NIAMSD, Flow Cytometry Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. EM liusheng.he@stjude.org RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU Intramural NIH HHS NR 53 TC 40 Z9 42 U1 0 U2 16 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 JUN PY 2006 VL 69A IS 6 BP 477 EP 486 DI 10.1002/cyto.a.20300 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049VR UT WOS:000238046200001 PM 16683263 ER PT J AU Parks, DR Roederer, M Moore, WA AF Parks, DR Roederer, M Moore, WA TI A new "Logicle" display method avoids deceptive effects of logarithmic scaling for low signals and compensated data SO CYTOMETRY PART A LA English DT Article DE data display; flow cytometry; fluorescence compensation; data scaling; data transformation AB Background: iIn immunofluorescence measurements and most other flow cytometry applications, fluorescence signals of interest can range down to essentially zero. After fluorescence compensation, some cell populations will have low means and include events with negative data values. Logarithmic presentation has been very useful in providing informative displays of wide-ranging flow cytometry data, but it fails to adequately display cell populations with low means and high variances and. in particular, offers no way to include negative data values. This has led to a great deal of difficulty in interpreting and understanding flow cytometry data, has often resulted in incorrect delineation of cell populations, and has led many people to question the correctness of compensation computations that were, in fact, correct. Results: We identified a set of criteria for creating data visualization methods that accommodate the scaling difficulties presented by flow cytometry data. On the basis of these, we developed,I new data visualization method that provides important advantages over linear or logarithmic scaling for display of flow cytometry data, a scaling we refer to as "Logicle" scaling. Logicle functions represent a particular generalization of the hyperbolic sine function with one more adjustable parameter than linear or logarithmic functions. Finally, we developed methods for objectively and automatically selecting an appropriate value for this parameter. Conclusions: The Logicle display method provides more complete, appropriate, and readily interpretable represenrations of data that includes populations with low-to-zero means, including distributions resulting from fluorescence compensation procedures, than can be produced using either logarithmic or linear displays. The method includes a specific algorithm for evaluating actual data distributions and deriving parameters of the Logicle scaling function appropriate for optimal display of that data. It is critical to note that Logicle visualization does not change the data values or the descriptive statistics computed front them. (c) 2006 International Society for Analytical Cytology. C1 Stanford Univ, Beckman Ctr, Dept Genet, Stanford, CA 94305 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Parks, DR (reprint author), Stanford Univ, Beckman Ctr, Dept Genet, B007, Stanford, CA 94305 USA. EM drparks@stanford.edu NR 8 TC 82 Z9 84 U1 0 U2 7 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 JUN PY 2006 VL 69A IS 6 BP 541 EP 551 DI 10.1002/cyto.20258 PG 11 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 049VR UT WOS:000238046200008 PM 16604519 ER PT J AU Mukhopadhyay, M Gorivodsky, M Shtrom, S Grinberg, A Niehrs, C Morasso, MI Westphal, H AF Mukhopadhyay, M Gorivodsky, M Shtrom, S Grinberg, A Niehrs, C Morasso, MI Westphal, H TI Dkk2 plays an essential role in the corneal fate of the ocular surface epithelium SO DEVELOPMENT LA English DT Article DE mouse; Dkk2; cornea; epidermis; differentiation; Wnt/beta-catenin ID HAIR FOLLICLE DEVELOPMENT; BETA-CATENIN; STEM-CELLS; DICKKOPF GENES; HEAD INDUCTION; BASAL CELLS; WNT SIGNALS; DIFFERENTIATION; MORPHOGENESIS; SKIN AB The Dkk family of secreted cysteine-rich proteins regulates Wnt/beta-catenin signaling by interacting with the Wnt co-receptor Lrp5/6. Here, we show that Dkk2-mediated repression of the Wnt/beta-catenin pathway is essential to promote differentiation of the corneal epithelial progenitor cells into a non-keratinizing stratified epithelium. Complete transformation of the corneal epithelium into a stratified epithelium that expresses epidermal-specific differentiation markers and develops appendages such as hair follicles is achieved in the absence of the Dkk2 gene function. We show that Dkk2 is a key regulator of the corneal versus epidermal fate of the ocular surface epithelium. C1 NIAMSD, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. RP Westphal, H (reprint author), NIAMSD, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. EM hw@mail.nih.gov FU Intramural NIH HHS NR 35 TC 79 Z9 83 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 1 PY 2006 VL 133 IS 11 BP 2149 EP 2154 DI 10.1242/dev.02381 PG 6 WC Developmental Biology SC Developmental Biology GA 041QW UT WOS:000237471800007 PM 16672341 ER PT J AU Glantz, MD Chambers, JC AF Glantz, Meyer D. Chambers, Jessica Campbell TI Prenatal drug exposure effects on subsequent vulnerability to drug abuse SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID SUBSTANCE USE DISORDERS; MATERNAL LIFE-STYLE; ANTISOCIAL PERSONALITY-DISORDER; CUMULATIVE ENVIRONMENTAL RISK; ADVERSE CHILDHOOD EXPERIENCES; GESTATIONAL COCAINE EXPOSURE; TOBACCO-SMOKE EXPOSURE; FETAL ALCOHOL SYNDROME; LOW-BIRTH-WEIGHT; OF-HOME CARE AB Research has shown that both prenatal alcohol and tobacco exposure are associated with increased risk of significant adverse medical, developmental, and behavioral outcomes including substance abuse. Research on the outcomes of prenatal exposure to illicit drugs (PNDE) has also found increased physical and behavioral problems for gestationally drug-exposed children. However, a clear picture has not emerged on whether the consequences of PNDE are independent from those associated with having a substance abusing parent and whether PNDE increases vulnerability to drug abuse. Because of its typical co-occurrence with factors inherent in having a drug-abusing parent, PNDE is at least a marker of significant increased risk for a range of negative outcomes including greater vulnerability to substance abuse. Although a review of the relevant research literatures indicates that the direct consequences of PNDE appear to be generally both subtle and nonglobal, PNDE does appear to have negative developmental and behavioral outcomes, and there is evidence that it is a modest direct contributor to increased substance abuse vulnerability. C1 Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Glantz, MD (reprint author), Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, 6001 Execut Blvd,Suite 5185,MSC 9589, Bethesda, MD 20892 USA. EM mglantz@nida.nih.gov NR 253 TC 21 Z9 21 U1 11 U2 24 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 SUM PY 2006 VL 18 IS 3 BP 893 EP 922 DI 10.1017/S0954579406060445 PG 30 WC Psychology, Developmental SC Psychology GA 074YY UT WOS:000239849800014 PM 17152406 ER PT J AU Miller, JL Macedonia, C Sonies, BC AF Miller, JL Macedonia, C Sonies, BC TI Sex differences in prenatal oral-motor function and development SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Article ID FETAL NEUROBEHAVIORAL DEVELOPMENT; UPPER AERODIGESTIVE TRACT; GENDER-DIFFERENCES; NONNUTRITIVE SUCKING; BIRTH; BEHAVIOR; CHILDREN; INFANTS; AGE; DISABILITY AB The aim of this study was to investigate sex-related differences in the prenatal development of early oral, lingual, pharyngeal, and laryngeal motor activities. Sonographic images of oral-upper airway regions were observed in 85 healthy fetuses (43 males, 42 females; mean gestational age 24wks 3d LSD 0.691; range 15-38wks). Biometric data on morphologic development and associated motor patterns were compared across second and third trimesters. Results showed that while males and females demonstrated statistically similar patterns of general physical growth (p > 0.05), significant differences in development of specific lingual and pharyngeal structures were present (p < 0.05). Significant differences were found for laryngeal and pharyngeal motor activity, and oral-lingual movements (p < 0.05). Complex oral-motor and upper airway skills emerged earlier in females, suggesting a sex-specific trajectory of motor development. It was concluded that differential patterns of prenatal motor development may be important in defining sex-specific indices of oral skill maturation. C1 NICHHD, Dept Hlth & Human Serv, NIH, Ctr Clin,Rehbail Med Dept,Phys Disabil Branch, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. RP Miller, JL (reprint author), NICHHD, Dept Hlth & Human Serv, NIH, Ctr Clin,Rehbail Med Dept,Phys Disabil Branch, Bldg 10,CRC RM 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. EM jmiller@cc.nih.gov FU Intramural NIH HHS NR 25 TC 15 Z9 16 U1 3 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD JUN PY 2006 VL 48 IS 6 BP 465 EP 470 DI 10.1017/S0012162206001009 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 050BI UT WOS:000238062100013 PM 16700938 ER PT J AU Ilnytska, O Lyzogubov, VV Stevens, MJ Drel, VR Mashtalir, N Pacher, P Yorek, MA Obrosova, IG AF Ilnytska, Olga Lyzogubov, Valeriy V. Stevens, Martin J. Drel, Viktor R. Mashtalir, Nazar Pacher, Pal Yorek, Mark A. Obrosova, Irina G. TI Poly(ADP-ribose) polymerase inhibition alleviates experimental diabetic sensory neuropathy SO DIABETES LA English DT Article ID OXIDATIVE-NITROSATIVE STRESS; ALDOSE REDUCTASE INHIBITION; ALPHA-LIPOIC ACID; PROTEIN-KINASE; PERIPHERAL NEUROPATHY; ENDOTHELIAL DYSFUNCTION; TRANSCRIPTION FACTORS; CONDUCTION-VELOCITY; NERVE CONDUCTION; NAD(P)H OXIDASE AB Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg. kg(-1) (.) day(-1) i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometertrigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADPribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses, including thermal and mechanical hyperalgesia and tactile allodynia as well as exaggerated formalin flinching behavior in diabetic rats, without affecting the aforementioned variables in the control group. Poly(ADP-ribose) and, to a lesser extent, nitrotyrosine abundance in sciatic nerve, as well as superoxide and nitrotyrosine formation in vasa nervorum, were markedly reduced by ISO therapy. Apoptosis in dorsal root ganglion neurons (transferase-mediated dUTP nick-end labeling assay) was not detected in any of the groups. In conclusion, PARP activation contributes to early diabetic sensory neuropathy by mechanisms that may include oxidative stress but not neuronal apoptosis. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIH, Lab Physiol Studies, NIAAA, Bethesda, MD 20892 USA. Univ Iowa, Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 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 Intramural NIH HHS [Z01 AA000375-02]; NIDDK NIH HHS [DK 071566-01, R21 DK071566] NR 51 TC 70 Z9 73 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2006 VL 55 IS 6 BP 1686 EP 1694 DI 10.2337/db06-0067 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YI UT WOS:000238053400017 PM 16731831 ER PT J AU Park, SW Goodpaster, BH Strotmeyer, ES de Rekeneire, N Harris, TB Schwartz, AV Tylavsky, FA Newman, AB AF Park, SW Goodpaster, BH Strotmeyer, ES de Rekeneire, N Harris, TB Schwartz, AV Tylavsky, FA Newman, AB TI Decreased muscle strength and quality in older adults with type 2 diabetes - The health, aging, and body composition study SO DIABETES LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc ID IMPAIRED GLUCOSE-TOLERANCE; SKELETAL-MUSCLE; MORPHOMETRIC ANALYSIS; INSULIN SENSITIVITY; ELDERLY-MEN; MASS; WOMEN; ASSOCIATION; DISABILITY; FAT AB Adequate skeletal muscle strength is essential for physical functioning and low muscle strength is a predictor of physical limitations. Older adults with diabetes have a two-to threefold increased risk of physical disability. However, muscle strength has never been investigated with regard to diabetes in a population-based study. We evaluated grip and knee extensor strength and muscle mass in 485 older adults with diabetes and 2,133 without diabetes in the Health, Aging, and Body Composition study. Older adults with diabetes had greater arm and leg muscle mass than those without diabetes because they were bigger in body size. Despite this, muscle strength was lower in men with diabetes and not higher in women with diabetes than corresponding counterparts. Muscle quality, defined as muscle strength per unit regional muscle mass, was significantly lower in men and women with diabetes than those without diabetes in both upper and lower extremities. Furthermore, longer duration of diabetes ( >= 6 years) and poor glycemic control (HbA(1c) > 8.0%) were associated with even poorer muscle quality. In conclusion, diabetes is associated with lower skeletal muscle strength and quality. These characteristics may contribute to the development of physical disability in older adults with diabetes. C1 Pochon CHA Univ, Dept Internal Med, Sungnam 463712, South Korea. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. NIA, Lab Epidemiol Demogr & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Park, SW (reprint author), Pochon CHA Univ, Dept Internal Med, 351 Yatapdong, Sungnam 463712, South Korea. EM parks@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU NIA NIH HHS [N01-AG-62101, N01-AG-62103, N01-AG-62106] NR 39 TC 184 Z9 189 U1 7 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2006 VL 55 IS 6 BP 1813 EP 1818 DI 10.2337/db05-1183 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YI UT WOS:000238053400033 PM 16731847 ER PT J AU Diego, VP Goring, HHH Cole, SA Almasy, L Dyer, TD Blangero, J Duggirala, R Laston, S Wenger, C Cantu, T Dyke, B North, K Schurr, T Best, LG Devereux, RB Fabsitz, RR Howard, BV MacCluer, JW AF Diego, VP Goring, HHH Cole, SA Almasy, L Dyer, TD Blangero, J Duggirala, R Laston, S Wenger, C Cantu, T Dyke, B North, K Schurr, T Best, LG Devereux, RB Fabsitz, RR Howard, BV MacCluer, JW TI Fasting insulin and obesity-related phenotypes are linked to chromosome 2p - The strong heart family study SO DIABETES LA English DT Article ID QUANTITATIVE TRAIT LOCUS; SERUM LEPTIN LEVELS; LINKAGE ANALYSIS; AMERICAN-INDIANS; CARDIOVASCULAR-DISEASE; RESISTANCE; GENETICS AB To localize quantitative trait loci for insulin metabolism and obesity, genome scans/linkage analyses were performed on > 900 members of 32 extended families participating in phase 3 of the Strong Heart Study, an investigation of the genetic and environmental determinants of cardiovascular disease in American-Indian populations from Arizona, Oklahoma, and North and South Dakota. Linkage analyses of fasting insulin and two obesity-related phenotypes, BMI and percent fat mass, were performed independently in each of the three populations. For log fasting insulin, we found a genome-wide maximum, robust logarithm of odds (LOD) score of 3.42 at 51 cM on, chromosome 2p in the Dakotas. Bivariate linkage analyses of log fasting insulin with both BMI and fat mass indicate a situation of incomplete pleiotropy, as well as several significant bivariate LOD scores in the Dakotas. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ Penn, Dept Anthropol, Philadelphia, PA 19104 USA. Missouri Breaks Ind Res, Timber Lake, SD USA. Cornell Univ, Med Ctr, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. MedStar Res Inst, Hyattsville, MD USA. RP Diego, VP (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM vdiego@darwin.sfbr.org RI Schurr, Theodore/A-1336-2007; OI Diego, Vincent/0000-0002-0007-2085 FU NHLBI NIH HHS [U01 HL41642, U01 HL65521, U01 HL41654, U01 HL065520, U01 HL41652, U01 HL65520]; NIMH NIH HHS [MH59490] NR 20 TC 8 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 2006 VL 55 IS 6 BP 1874 EP 1878 DI 10.2337/db05-0668 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YI UT WOS:000238053400042 PM 16731856 ER PT J AU Cowie, CC Engelgau, MM Rust, KF Saydah, SH Byrd-Holt, DD Williams, DE Eberhardt, MS Geiss, LS Flegal, KM Gregg, EW AF Cowie, CC Engelgau, MM Rust, KF Saydah, SH Byrd-Holt, DD Williams, DE Eberhardt, MS Geiss, LS Flegal, KM Gregg, EW TI Prevalence of diabetes and impaired fasting glucose in adults in the US population - National Health and Nutrition Examination Survey 1999-2002 SO DIABETES CARE LA English DT Article ID INTERVENTION; TOLERANCE; OBESITY; TRENDS AB OBJECTIVE- The purpose of this study was to examine the prevalences of diagnosed and undiagnosed diabetes, and impaired fasting glucose (IFG) in U.S. adults during 1999-2002, and compare prevalences to those in 1988-1994. RESEARCH DESIGN AND METHODS- The National Health and Nutrition Examination Survey (NHANES) contains a probability sample of adults aged >= 20 years. In the NHANES 1999-2002, 4,761 adults were classified on glycemic status using standard criteria, based on an interview for diagnosed diabetes and fasting plasma glucose measured in a subsample. RESULTS- The crude prevalence of total diabetes in 1999-2002 was 9.3% (19.3 million, 2002 U.S. population), consisting of 6.5% diagnosed and 2.8% undiagnosed. An additional 26.0% had IFG, totaling 35.3% (73.3 million) with either diabetes or IFG. The prevalence Of total diabetes rose with age, reaching 21.6% for those aged >= 65 years. The prevalence of diagnosed diabetes was twice as high in non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites (both P < 0.00001), whereas the prevalence of undiagnosed diabetes was similar by race/ethnicity, adjusted for age and sex. The prevalence of diagnosed diabetes was similar by sex, but prevalences of undiagnosed diabetes and IFG were significantly higher in men. The crude prevalence of diagnosed diabetes rose significantly from 5.1% in 1988-1994 to 6.5% in 1999-2002, but the crude prevalences were stable for undiagnosed diabetes (from 2.7 to 2.8%) and lFG (from 24.7 to 26,0%). Results were similar after adjustment for age and sex. CONCLUSIONS- Although the prevalence of diagnosed diabetes has increased significantly over the last decade, the prevalences of undiagnosed diabetes and IFG have remained relatively stable. Minority groups remain disproportionately affected. C1 NIDDK, Diabet Epidemiol Program, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Social & Sci Syst, Silver Spring, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Cowie, CC (reprint author), NIDDK, Diabet Epidemiol Program, NIH, 6707 Democracy Blvd,Rm 691,MSC 5460, Bethesda, MD 20892 USA. EM cowiec@mail.nih.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 22 TC 746 Z9 763 U1 4 U2 24 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 JUN PY 2006 VL 29 IS 6 BP 1263 EP 1268 DI 10.2337/dc06-0062 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200012 PM 16732006 ER PT J AU Brown, JS Vittinghoff, E Lin, F Nyberg, LM Kusek, JW Kanaya, AM AF Brown, JS Vittinghoff, E Lin, F Nyberg, LM Kusek, JW Kanaya, AM TI Prevalence and risk factors for urinary incontinence in women with type 2 diabetes and impaired fasting glucose: findings from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 SO DIABETES CARE LA English DT Article ID LIFE-STYLE INTERVENTION; WEIGHT-LOSS; PREVENTION; MELLITUS; COMPLICATIONS; DIAGNOSIS; DISEASE; IMPACT; HEART AB OBJECTIVE - Diabetes is associated with increased risk of urinary incontinence. It is unknown whether women with pre-diabetes, or impaired fasting glucose (IFG), have increased prevalence of incontinence. We determined the prevalence of, and risk factors for, incontinence among U.S. women with diabetes and IFG. RESEARCH DESIGN AND METHODS - The 2001-2002 National Health and Nutrition Examination Survey measured fasting plasma glucose and obtained information about diabetes and urinary incontinence among 1,461 nonpregnant adult women. Self-reported weekly or more frequent incontinence, both overall and by type (urge and stress), was our outcome. RESULTS - Of the 1,461 women, 17% had diabetes and 11% met criteria for IFG. Prevalence of weekly incontinence was similar among women in these two groups (35.4 and 33.4%, respectively) and significantly higher than among women with normal fasting glucose (16.8%). both urge and stress incontinence were increased. In addition to well-recognized risk factors including age, weight, and oral estrogen use, two microvascular complications caused by diabetes, specifically macroalbuminuria and peripheral neuropathic pain, were associated With incontinence. CONCLUSIONS - Physicians should be alert for incontinence, an often unrecognized and therefore undertreated disorder, among women with diabetes and IFG, in particular those with microvascular complications. The additional prospect of improvements in their incontinence may help motivate some high-risk women to undertake difficult lifestyle changes to reduce their more serious risk of diabetes and its sequelae. C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. NIDDK, NIH, Bethesda, MD USA. RP Brown, JS (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM brownj@obgyn.ucsf.edu FU NIDDK NIH HHS [P50 DK064538]; PHS HHS [K24 PA 98053] NR 24 TC 70 Z9 74 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 JUN PY 2006 VL 29 IS 6 BP 1307 EP 1312 DI 10.2337/dc05-2463 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 049YG UT WOS:000238053200019 PM 16732013 ER PT J AU Compton, WA Volkow, ND AF Compton, WA Volkow, ND TI Abuse of prescription drugs and the risk of addiction SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE prescription drug abuse; drug dependence; addiction; opioid analgesic ID SUBSTANCE-ABUSE; COCAINE; COCAETHYLENE; METABOLISM; METHADONE; DIAZEPAM; ALCOHOL; HUMANS; ADHD AB Abuse of several categories of prescription drugs has increased markedly in the United States in the past decade and is now at alarming levels for certain agents, especially opioid analgesics and stimulants. Prescription drugs of abuse fit into the same pharmacological classes as their non-prescription counterparts. Thus, the potential factors associated with abuse or addiction versus safe therapeutic use of these agents relates to the expected variables: dose, route of administration, co-administration with other drugs, context of use, and expectations. Future scientific work on prescription drug abuse will include identification of clinical practices that minimize the risks of addiction, the development of guidelines for early detection and management of addiction, and the development of clinically effective agents that minimize the risks for abuse. With the high rates of prescription drug abuse among teenagers in the United States, a particularly urgent priority is the investigation of best practices for effective prevention and treatment for adolescents, as well as the development of strategies to reduce diversion and abuse of medications intended for medical use. Published by Elsevier Ireland Ltd. C1 NIDA, Dept Hlth & Human Sci, NIH, Bethesda, MD 20892 USA. RP Compton, WA (reprint author), NIDA, Dept Hlth & Human Sci, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM wcompton@mda.nih.gov NR 28 TC 198 Z9 200 U1 7 U2 27 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN PY 2006 VL 83 SU 1 BP S4 EP S7 DI 10.1016/j.drugalcdep.2005.10.020 PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 043JX UT WOS:000237598400002 PM 16563663 ER PT J AU Daly, JW Camerini-Otero, CS AF Daly, John W. Camerini-Otero, Carol S. TI Imidazole-induced elevations of intracellular calcium in HL-60 cells: Effect of inhibition of phospholipase C by the steroidal maleimide U73122 SO DRUG DEVELOPMENT RESEARCH LA English DT Review DE capacitative calcium entry; miconazole; SKF 96365; clotrimazole; calmidazolium; phospholipase C; U73122; thapsigargin; SOC channels ID CAPACITATIVE CA2+ ENTRY; CANINE KIDNEY-CELLS; PANCREATIC ACINAR-CELLS; PROTEIN-KINASE-C; HUMAN OSTEOSARCOMA CELLS; HAMSTER OVARY CELLS; PI-PLC INHIBITORS; MDCK CELLS; CYTOSOLIC CALCIUM; PHOSPHOINOSITIDE HYDROLYSIS AB A variety of agents, including imidazoles, such as miconazole, elicit elevations of calcium in human leukemic HL-60 cells through a stimulation of influx of calcium and/or a release of intracellular calcium. Release of intracellular calcium by such agents may involve stimulation of IP3 formation. The steroidal maleimide U73122, a potent phospholipase C (PLC) inhibitor, at 3-10 mu M blocked elevations of calcium elicited in HL-60 cells by ATP. At a 10 mu M concentration, U73122 either blocked or altered elevations of calcium elicited by imidazoles, such as miconazole, SKF 96365, and clotrimazole that are often used to block capacitative calcium entry, and by calmidazolium, a quaternary imidazole that can trigger massive influx of calcium in HL-60 cells. Elevations of calcium elicited by thapsigargin were not affected by 3 mu M U73122, but were reduced by higher concentrations. Remarkably, U73122 at 10 mu M did not block, but instead slowed and potentiated the elevation of calcium elicited by higher concentrations of imidazoles, an effect that may involve inhibition of Ca2+-ATPases of the endoplasmic reticulum. The steroidal succinimide U73343 had minimal effects on calcium elevations in HL-60 cells. The results indicate that U73122 requires cautious use in assessing the role of PLC in controlling calcium levels in HL-60 cells, in particular when used with imidazoles, such as SKF 96365, which are used to block capacitative calcium entry. The effects of U73122 on cell calcium are reviewed. In toto, the results suggest that many lipophilic agents may affect intracellular calcium by activating PLC through unknown mechanisms. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 116 TC 0 Z9 0 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD JUN PY 2006 VL 67 IS 6 BP 519 EP 534 DI 10.1002/ddr.20111 PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 097JY UT WOS:000241444700005 ER PT J AU Colburn, NH Yang, HS Jansen, A AF Colburn, Nancy H. Yang, Hsin-Sheng Jansen, Aaron TI Pdcd4 targets eIF4A to inhibit translation, transcription, tumorigenesis, and invasion SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Lab Canc Prevent, Frederick, MD 21702 USA. NR 6 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA S52 BP 23 EP 23 DI 10.1016/j.ejcsup.2006.04.053 PG 1 WC Oncology SC Oncology GA 062UF UT WOS:000238969500054 ER PT J AU Leupold, JL Yang, HS Colburn, NH Boyd, DD Lengyel, ER Post, S Allgayer, H AF Leupold, J. L. Yang, H. S. Colburn, N. H. Boyd, D. D. Lengyel, E. R. Post, S. Allgayer, Heike TI Tumor suppressor Pdcd4 inhibits invasion and regulates urokinase-receptor (u-PAR) gene expression via Sp-transcription factors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Heidelberg, Dept Expt Surg & Mol Oncol Solid Tumors, Klinikum Mannheim, D-6900 Heidelberg, Germany. DKFZ Heidelberg, Heidelberg, Germany. NCI, Gene Regulat Sect, Basic Res Lab, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Heidelberg, Klinikum Mannheim, Dept Surg, D-6900 Heidelberg, Germany. RI Lengyel, Ernst/D-9220-2014 OI Lengyel, Ernst/0000-0001-8624-1507 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA P4 BP 28 EP 28 DI 10.1016/j.ejcsup.2006.04.064 PG 1 WC Oncology SC Oncology GA 062UF UT WOS:000238969500064 ER PT J AU Medved, F Grobholz, R Jost, C Mudduluru, G Leupold, JH Schumacher, J Colburn, NH Post, S Allgayer, H AF Medved, F. Grobholz, R. Jost, C. Mudduluru, G. Leupold, J. H. Schumacher, J. Colburn, N. H. Post, S. Allgayer, H. TI Evidence of Pdcd 4 as a novel marker for tumor diagnosis and progression in resected colorectal carcinomas SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Heidelberg, Dept Expt Surg Mannheim, D-6900 Heidelberg, Germany. DKFZ Heidelberg, Mol Oncol Solid Tumors Unit, D-68135 Mannheim, Germany. Univ Heidelberg, Dept Pathol Mannheim, D-68135 Mannheim, Germany. Univ Heidelberg, Dept Surg, Klinikum Mannheim, D-68135 Mannheim, Germany. Natl Canc Inst, Ctr Canc Res, Lab Canc Prevent, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA P5 BP 28 EP 29 DI 10.1016/j.ejcsup.2006.04.065 PG 2 WC Oncology SC Oncology GA 062UF UT WOS:000238969500065 ER PT J AU Grade, M Liersch, T Varma, S Difilippantonio, MJ Langer, C Simon, R Ried, T Becker, H Ghadimi, BM AF Grade, Marian Liersch, Torsten Varma, Sudhir Difilippantonio, Michael J. Langer, Claus Simon, Richard Ried, Thomas Becker, Heinz Ghadimi, B. Michael TI Pretherapeutical gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy and its impact on disease free survival SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Gottingen, Med Ctr, Dept Gen Surg, D-3400 Gottingen, Germany. Natl Canc Inst, Genet Branch, NIH, Bethesda, MD USA. Natl Canc Inst, Biometr Res Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA P67 BP 51 EP 52 DI 10.1016/j.ejcsup.2006.04.127 PG 2 WC Oncology SC Oncology GA 062UF UT WOS:000238969500127 ER PT J AU Habermann, JK Paulsen, U Roblick, U Upender, MB McShane, L Korn, EL Wangsa, D Duchrow, M Krueger, S Bruch, HP Auer, G Ried, T AF Habermann, J. K. Paulsen, U. Roblick, U. Upender, M. B. McShane, L. Korn, E. L. Wangsa, D. Duchrow, M. Krueger, S. Bruch, H. -P. Auer, G. Ried, T. TI Gene expression signature of colorectal carcinogenesis SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Genet Branch, NIH, Bethesda, MD USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Pathol & Oncol, Unit Canc Proteom, Stockholm, Sweden. 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD JUN PY 2006 VL 4 IS 6 MA P68 BP 52 EP 52 DI 10.1016/j.ejcsup.2006.04.128 PG 1 WC Oncology SC Oncology GA 062UF UT WOS:000238969500128 ER PT J AU Yang, QF Kim, YS Lin, Y Lewis, J Neckers, L Liu, ZG AF Yang, QF Kim, YS Lin, Y Lewis, J Neckers, L Liu, ZG TI Tumour-necrosis-factor-receptor-1 mediates endoplasmic reticulum stress-induced activation of the MAP kinase JNK SO EMBO REPORTS LA English DT Article DE ER stress; JNK; RIP; TNFR1 ID TUMOR-NECROSIS-FACTOR; UNFOLDED PROTEIN RESPONSE; DEATH-DOMAIN KINASE; KAPPA-B ACTIVATION; INDUCED CELL-DEATH; N-TERMINAL KINASE; FACTOR-RECEPTOR; TRANSLATIONAL CONTROL; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION AB Tumour necrosis factor receptor (TNFR) 1 is the main receptor responsible for TNF-induced diverse cellular events. In this study, we report that TNFR1 has a crucial role in endoplasmic reticulum (ER) stress-induced Jun amino-terminal kinase (JNK) activation. Although ER stress leads to JNK activation in wild-type mouse embryo fibroblasts, we failed to detect any JNK activation in TNFR1-/ - cells. ER stress-induced JNK activation is restored in TNFR1-/- cells when TNFR1 expression is reconstituted. We also found that TNFR1 functions downstream of IRE1 and that IRE1 is present in the same complex with TNFR1 under ER stress condition. Therefore, our study shows a novel role of TNFR1 in mediating ER stress-induced JNK activation. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU Intramural NIH HHS NR 36 TC 37 Z9 39 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUN PY 2006 VL 7 IS 6 BP 622 EP 627 DI 10.1038/sj.embor.7400687 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 059BE UT WOS:000238707500014 PM 16680093 ER EF