FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Goncalves, RS Fernandez-Vina, M Lewinsohn, DM Sztein, MB AF Goncalves, RS Fernandez-Vina, M Lewinsohn, DM Sztein, MB TI Identification of a human HLA-E-restricted CD8(+) T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Georgetown Univ, Naval Med Res Ctr, Bill Young DoD Marrow Donor Program, Kensington, MD, Australia. Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A800 EP A800 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700195 ER PT J AU Hattori, M Noso, S Hattori, K Lund, T Sharma, A Li, Q Flavell, R Wakeland, W AF Hattori, M Noso, S Hattori, K Lund, T Sharma, A Li, Q Flavell, R Wakeland, W TI MHC-linked type 1 diabetogenic genes Idd1c and Idd1d may be related to apoptosis of islet beta cells in the NOD mouse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC C1 Joslin Diabet Ctr, Boston, MA 02215 USA. UCL, London WC1E 6BT, England. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75230 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. London MA, London, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A841 EP A841 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700399 ER PT J AU Ho, RC Farmer, JR Hirshman, MF Sakamoto, K Aschenbach, WG Goodyear, LJ AF Ho, RC Farmer, JR Hirshman, MF Sakamoto, K Aschenbach, WG Goodyear, LJ TI Skeletal muscle I kappa B kinase is regulated by exercise and contraction via ERK- and p38 MAPK-dependent mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1293 EP A1293 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702552 ER PT J AU Hsu, HC Yang, P Wu, Q Zhou, JL Zhang, HG Mountz, JD AF Hsu, HC Yang, P Wu, Q Zhou, JL Zhang, HG Mountz, JD TI BXD2, a novel generalized autoimmune mouse model that develops both lupus and erosive arthritis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A836 EP A836 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700374 ER PT J AU Ichinose, F Beppu, H Jones, RC Kawai, N Li, E Zapol, WM Bloch, KD AF Ichinose, F Beppu, H Jones, RC Kawai, N Li, E Zapol, WM Bloch, KD TI Altered pulmonary hemodynamics and structure in mice heterozygous for bone morphogenetic protein type II receptor (BMPR2) gene SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1053 EP A1053 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701407 ER PT J AU Kwak, HK Milbury, PE Blumberg, JB Ning, MM Hubbard, J Furie, KL Kelly, PJ AF Kwak, HK Milbury, PE Blumberg, JB Ning, MM Hubbard, J Furie, KL Kelly, PJ TI Early depletion of endogenous antioxidant status following acute ischemic stroke in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A909 EP A909 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700718 ER PT J AU Lee, HH Li, LQ Bell, JJ Gregg, RK Zaghouani, H AF Lee, HH Li, LQ Bell, JJ Gregg, RK Zaghouani, H TI Selective expression of IL-13R alpha 1 on neonatal Th1 cells bias secondary responses towards Th2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Missouri, Columbia, MO 65212 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1170 EP A1170 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701966 ER PT J AU Liu, ZY David, CS Liu, CR Xu, X Wang, JH Yang, P Yu, SH Hsu, H Mountz, JD Zhang, HG AF Liu, ZY David, CS Liu, CR Xu, X Wang, JH Yang, P Yu, SH Hsu, H Mountz, JD Zhang, HG TI Deletion of epitope specific T cells using CII peptide-DC-AdTRAIL results in the prevention of CII induced arthritis in DQ8 transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Dept Med, Birmingham VAMC, Birmingham, AL 35294 USA. Mayo Clin & Mayo Fdn, Dept Med, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1173 EP A1174 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701982 ER PT J AU Mascarenhas, MM Garg, HG Hales, CA Quinn, DA AF Mascarenhas, MM Garg, HG Hales, CA Quinn, DA TI Stretch-induced low molecular weight hyaluronan (LMW HA) activates phospho-JNK and NF kappa B/I kappa B in LMW HA induced IL-8 production in bronchiolar epithelial cells (BEAS-2B) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1053 EP A1053 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701406 ER PT J AU McIntire, JJ Umetsu, SE Macaubas, C Hoyte, E Cinnioglu, C Cavalli-Sforza, LL Barsh, GS Hallmayer, JF Underhill, PA Risch, NJ Freeman, GJ DeKruyff, RH Umetsu, DT AF McIntire, JJ Umetsu, SE Macaubas, C Hoyte, E Cinnioglu, C Cavalli-Sforza, LL Barsh, GS Hallmayer, JF Underhill, PA Risch, NJ Freeman, GJ DeKruyff, RH Umetsu, DT TI Association of TIM-1 with atopy: Gene interaction with hepatitis A infection and the hygiene hypothesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Stanford Univ, Sch Med, Palo Alto, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A817 EP A817 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700279 ER PT J AU Mountz, JD Zhou, T Yang, P Wu, Q Zhou, JL Zhang, Y Zhang, HG Hsu, HC AF Mountz, JD Zhou, T Yang, P Wu, Q Zhou, JL Zhang, Y Zhang, HG Hsu, HC TI The generalized autoimmune disease developed by the BXD2 mouse strain is associated with upregulation of BAFF receptor and increased B-cell response to both CD40 and IgM SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A838 EP A838 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700381 ER PT J AU Nagler-Anderson, C Shi, HN Zhu, WS Louie, S Bashir, MEH AF Nagler-Anderson, C Shi, HN Zhu, WS Louie, S Bashir, MEH TI TLR-4 signaling by intestinal microbes influences susceptibility to food allergy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Massachusetts Gen Hosp, Ped GI, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A817 EP A817 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700280 ER PT J AU Pena, JR Goldspink, PH Prabhakar, R del Monte, F Hajjar, RJ Wieczorek, DF Wolska, BM AF Pena, JR Goldspink, PH Prabhakar, R del Monte, F Hajjar, RJ Wieczorek, DF Wolska, BM TI Neonatal gene transfer of SERCA2a improves the response to beta-adrenergic stimulation in a FHC alpha-tropomyosin (Glu180Gly) mouse model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Illinois, Chicago, IL 60612 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1216 EP A1217 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702188 ER PT J AU Rattan, R Giri, S Singh, A Singh, I AF Rattan, R Giri, S Singh, A Singh, I TI Rho A negatively regulates cytokine-mediated inducible-Nitric Oxide Synthase expression in brain derived transformed cell lines: Negative regulation of IKK alpha SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A992 EP A992 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701110 ER PT J AU Salamanca, DA Khalil, RA AF Salamanca, DA Khalil, RA TI Increased [Ca2+]i in renal arterial smooth muscle cells during interleukin-6 induced hypertension in pregnant rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 VA Boston Healthcare Syst, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1239 EP A1240 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702296 ER PT J AU Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JA Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM AF Torres-Vazquez, J Gitler, AD Fraser, SD Berk, JA Pham, VN Fishman, MC Childs, S Epstein, JA Weinstein, BM TI Patterning and guidance of the vertebrate trunk angiogenic vasculature SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada. Univ Calgary, Smooth Muscle Res Grp, Calgary, AB T2N 1N4, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Penn, Sch Med, Mol Cardiol Res Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A777 EP A777 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470700080 ER PT J AU Wang, HW Mitchell, H Babic, A Saffaripour, S Wagner, DD AF Wang, HW Mitchell, H Babic, A Saffaripour, S Wagner, DD TI Soluble ICAM-1 modulates immune responses and fat metabolism in transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1145 EP A1145 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701845 ER PT J AU Young, MRI AF Young, MRI TI Tumor blood vessel development by vasculogenesis, not only angiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1181 EP A1181 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470702019 ER PT J AU Zhang, HG Hsu, HC Yang, P Wu, Q Yu, SH High, KA Mountz, JD AF Zhang, HG Hsu, HC Yang, P Wu, Q Yu, SH High, KA Mountz, JD TI Significant linkage of the anti-AAV immune response to loci on mouse chromosomes (Chr) 12 and 17 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1142 EP A1142 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701829 ER PT J AU Zhang, M Alicot, E Moore, F Leung, H Carroll, MC AF Zhang, M Alicot, E Moore, F Leung, H Carroll, MC TI Binding of natural antibody to endothelium promotes ischemia-reperfusion injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Nat Antibodies Inc, Pathol, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. CBR Inst Biomed Res Inc, Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 24 PY 2004 VL 18 IS 5 SU S BP A1162 EP A1162 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZB UT WOS:000220470701925 ER PT J AU Rowe, S MacLean, CH Shekelle, PG AF Rowe, S MacLean, CH Shekelle, PG TI Preventing visual loss from chronic eye disease in primary care - Scientific review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID BEAVER DAM EYE; TREATMENT DIABETIC-RETINOPATHY; AGE-RELATED MACULOPATHY; RETINAL VEIN OCCLUSION; ATHEROSCLEROTIC CARDIOVASCULAR-DISEASE; ISCHEMIC OPTIC NEUROPATHY; CAUSE-SPECIFIC PREVALENCE; OPEN-ANGLE GLAUCOMA; RISK-FACTORS; MACULAR DEGENERATION AB Context Vision loss is common in the United States and its prevalence increases with age. Visual disability significantly impacts quality of life and increases the risk of injury. Although at least 40% of blindness in the United States is either preventable or treatable with timely diagnosis and intervention, many people with vision loss are undiagnosed and untreated. Objective To review the evidence regarding screening and management of eye disorders and visual disability among adults in the primary care setting. Data Sources and Study Selection MEDLINE, HealthSTAR, EMBASE, The Cochrane Database of Systematic Reviews, and the National Guidelines Clearinghouse were searched for articles and practice guidelines about screening and management of eye diseases and vision loss among adults in the primary care setting using key words and free-text terms, such as vision screening, glaucoma prevention and control, from 1985 to 2003. References in these articles and those suggested by experts in eye care, vision loss, and vision screening were reviewed as well. Data Extraction Articles were Searched for the most clinically important information and emphasized randomized controlled trials where available. Data Synthesis Most major guidelines recommend periodic referral of older adults to an eye care professional for comprehensive evaluation to detect eye diseases and visual disability. The value of routine screening for vision loss in the primary care setting has not been established. Timely identification and treatment of eye diseases can substantially reduce the incidence and prevalence of visual disability among-older adults. Optimizing management of systemic diseases, such as diabetes, hypertension, and hyperlipidemia, significantly reduces the risk of related eye disorders. Conclusions Primary care clinicians can play a vital role in preserving vision in their patients by managing systemic diseases that impact eye health and by ensuring that patients undergo periodic evaluations by eye care professionals and receive needed eye care. C1 Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02119 USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Hlth Care Syst, Dept Med, Los Angeles, CA USA. RP Rowe, S (reprint author), Boston Univ, Sch Med, Dept Ophthalmol, Room L-907,720 Harrison Ave, Boston, MA 02119 USA. EM srowe@bu.edu NR 121 TC 47 Z9 49 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 2004 VL 291 IS 12 BP 1487 EP 1496 DI 10.1001/jama.291.12.1487 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 805UI UT WOS:000220390800030 PM 15039416 ER PT J AU Goldzweig, CL Rowe, S Wenger, NS MacLean, CH Shekelle, PG AF Goldzweig, CL Rowe, S Wenger, NS MacLean, CH Shekelle, PG TI Preventing and managing visual disability in primary care - Clinical applications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID QUALITY-OF-LIFE; AGE-RELATED MACULOPATHY; SELF-RATED VISION; BEAVER DAM EYE; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; FUNCTIONAL STATUS; RISK-FACTORS; CATARACT-EXTRACTION; SMOKING-CESSATION AB Clinicians in primary care settings are well positioned to participate in the prevention and management of visual disability. They can have a significant impact on their patients' visual health by screening for vision problems, aggressively controlling known risk factors for visual loss, ensuring adherence to ophthalmologic treatment and continuity of eye care, and by timely referral of specific patient populations to qualified eye care professionals (eg, ophthalmologists and optometrists). Using their knowledge about common ophthalmic medications, clinicians can detect adverse effects of these agents, including exacerbations of heart or lung disease. They can ensure that appropriate patients are screened for common serious eye diseases, such as glaucoma, and that patients with disabilities related to vision problems are assessed for treatable conditions, such as cataracts or refractive error. Finally, clinicians can direct patients with low vision from any cause to resources designed to help enhance patient function and emotional support. C1 Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RAND Hlth, Santa Monica, CA USA. RP Goldzweig, CL (reprint author), Vet Affairs W Los Angeles Healthcare Ctr, 111-G, Los Angeles, CA 90073 USA. EM goldzweig@med.va.gov NR 47 TC 17 Z9 18 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 2004 VL 291 IS 12 BP 1497 EP 1502 DI 10.1001/jama.291.12.1497 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 805UI UT WOS:000220390800031 PM 15039417 ER PT J AU Whang, W Mittleman, MA Rich, DQ Wang, PJ Ruskin, JN Tofler, GH Muller, JE Albert, CM AF Whang, W Mittleman, MA Rich, DQ Wang, PJ Ruskin, JN Tofler, GH Muller, JE Albert, CM CA TOVA Investigators TI Heart failure and the risk of shocks in patients with implantable cardioverter defibrillators - Results from the Triggers of Ventricular Arrhythmias (TOVA) study SO CIRCULATION LA English DT Article DE heart failure; tachyarrhythmias; defibrillation; cardioversion ID SEVERE IMPAIRMENT; SUDDEN-DEATH; PREDICTORS; THERAPY; BENEFIT; SURVIVAL; TRIAL; RECURRENCE; MECHANISMS; DISCHARGE AB Background - Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter- defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear. Methods and Results - We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF ( hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF < 0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF ( hazard ratio 3.90, 95% CI 1.28 to 11.92). Conclusions - Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined. C1 Massachusetts Gen Hosp, Cardiac Unit, Div Cardiovasc, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Royal N Shore Hosp, Sydney, NSW, Australia. RP Whang, W (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Div Cardiovasc, Bulfinch 001,55 Fruit St, Boston, MA 02114 USA. EM wwhang@partners.org FU NHLBI NIH HHS [5R01-HL041016] NR 27 TC 67 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 2004 VL 109 IS 11 BP 1386 EP 1391 DI 10.1161/01.CIR.0000120703.99433.1E PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 805KH UT WOS:000220364700011 PM 14993132 ER PT J AU Corcoran, LJ Mitchison, TJ Liu, Q AF Corcoran, LJ Mitchison, TJ Liu, Q TI A novel action of histone deacetylase inhibitors in a protein aggresome disease model SO CURRENT BIOLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE PROTEINS; ALS-LINKED SOD1; MISFOLDED PROTEINS; HEAT-SHOCK; AGGREGATION; TOXICITY; STRESS AB Protein inclusions are associated with a number of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) [1]. Whether protein aggregates are toxic or beneficial to cells is not known. In ALS animal models, mutant SOD1 forms aggresome-like structures in motor neurons and astrocytes [2, 3]. To better understand the role of protein aggregation in the progression of disease etiology, we performed a screen for small molecules that disrupt aggresome formation in cultured cells. After screening 20,000 compounds, we obtained two groups of compounds that specifically prevented aggresome formation. One group consists mainly of cardiac glycosides and will be the subject of another study. The second group contains two compounds: one is a known histone deacetylase (HDAC) inhibitor, Scriptaid [4], and the other is a Flavin analog, DPD. Cells treated with these molecules still contained microaggregates, but these microaggregates were not transported to microtubule organizing centers (MTOCs). The defect in transport was linked to modulation of the dynein/dynactin machinery as treatment with Scriptaid or DPD reversed mSOD-induced insolubilization of the dynactin subunits P50 dynamitin and P150(glued). Our findings suggest a connection between HDAC activity and aggresome formation and also lay the groundwork for a direct test of the role of aggresome formation in ALS etiology. C1 Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Liu, Q (reprint author), Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. EM ching_liu@hms.harvard.edu NR 17 TC 59 Z9 59 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 23 PY 2004 VL 14 IS 6 BP 488 EP 492 DI 10.1016/j.cub.2004.03.003 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 808RZ UT WOS:000220587500021 PM 15043813 ER PT J AU Blackwell, TK AF Blackwell, TK TI Germ cells: Finding programs of mass repression SO CURRENT BIOLOGY LA English DT Editorial Material ID ZYGOTIC GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; NONCODING RNA; C-ELEGANS; TRANSCRIPTION; EMBRYOS; LINEAGE; ESTABLISHMENT; NANOS AB Transcription is globally silenced in the germline of animals. Recent studies have shown that, in Caenorhabditis elegans, this silencing is initially mediated through direct repression, but in Drosophila, the factors involved include pgc, a non-coding cytoplasmic RNA. Why are these mechanisms so diverse and complex? C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. NR 19 TC 25 Z9 25 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 MAR 23 PY 2004 VL 14 IS 6 BP R229 EP R230 DI 10.1016/j.cub.2004.02.052 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 808RZ UT WOS:000220587500008 PM 15043831 ER PT J AU Arnolds, D Sakamoto, K Ekberg, I Thore, A Goodyear, LJ AF Arnolds, D Sakamoto, K Ekberg, I Thore, A Goodyear, LJ TI Exercise regulates Akt, GSK3, and beta-catenin signaling in human skeletal muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Joslin Diabet Ctr, Res Div, Boston, MA 02215 USA. Karolinska Inst, Ersta Hosp, S-10401 Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A356 EP A356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601714 ER PT J AU Bin, OY Jafari, B Syrkina, O Hales, CA Quinn, DA AF Bin, OY Jafari, B Syrkina, O Hales, CA Quinn, DA TI N-acetyl-L-eysteine (NAC) inhibited TGF-beta production and reduced lung collagen formation in ventilator induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A323 EP A324 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601557 ER PT J AU Birdsall, HH Green, DM Porter, W Lee, C Rubio, JA Trial, J Rossen, RD AF Birdsall, HH Green, DM Porter, W Lee, C Rubio, JA Trial, J Rossen, RD TI Impact of fibronectin fragments on the transendothelial migration of HIV-infected leukocytes and the development of subendothelial foci of infectious leukocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Houston VAMC, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A457 EP A457 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602203 ER PT J AU Bowser, RP Ranganathan, S Day, BW Cudkowicz, ME Brown, RH AF Bowser, RP Ranganathan, S Day, BW Cudkowicz, ME Brown, RH TI Proteomic profiling of cerebrospinal fluid to identify diagnostic biomarkers for amyotrophic lateral sclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 16066 USA. Massachusetts Gen Hosp, Day Neuromusc Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A199 EP A199 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600952 ER PT J AU Cavanagh, L Bonasio, R Van der Velden, A Mazo, IB Cariappa, A Starnbach, M Pillai, S Weninger, W von Andrian, UH AF Cavanagh, L Bonasio, R Van der Velden, A Mazo, IB Cariappa, A Starnbach, M Pillai, S Weninger, W von Andrian, UH TI A novel route of dendritic cell migration resulting in the activation of memory T cells in the bone marrow SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A448 EP A448 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602159 ER PT J AU Chaker, A Gentile, M Salahuddin, S Yano, X Drews, R Yunis, EJ Schnitt, SJ Schnipper, LE AF Chaker, A Gentile, M Salahuddin, S Yano, X Drews, R Yunis, EJ Schnitt, SJ Schnipper, LE TI SMARCAD1 interacts with proteins involved in the processes of transcriptional activation, DNA replication and repair mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A572 EP A572 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602742 ER PT J AU Chew, DKW Khalil, RA AF Chew, DKW Khalil, RA TI Matrix metalloproteinase-9 promotes aortic dilation by inhibiting Ca2(+) influx into vascular smooth muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A284 EP A284 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601369 ER PT J AU Daly, C Dube, C Rollins, BJ AF Daly, C Dube, C Rollins, BJ TI APC-derived monocyte chemoattractant protein-1 (MCP-1/CCL2) provides costimulatory activity for CD4 cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02135 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A465 EP A466 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602244 ER PT J AU Das, S Husain, Z Alper, C Dubey, D AF Das, S Husain, Z Alper, C Dubey, D TI Parallel analysis of multiple cytokine and chemokine production upon triggering of NK receptors on human NK cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A52 EP A53 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600259 ER PT J AU Eggenschwiler, J Li, T Anderson, K AF Eggenschwiler, J Li, T Anderson, K TI Regulation of hedgehog signaling in dorso-ventral patterning of the mouse neural tube SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Princeton Univ, Lewis Thomas Lab, Princeton, NJ 08544 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Retinal Degenerat, Boston, MA USA. Sloan Kettering Inst, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A18 EP A18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600084 ER PT J AU Gauguet, JM Marth, JD von Andrian, UH AF Gauguet, JM Marth, JD von Andrian, UH TI Core2GlcNAcT-I elaboration of HEV L-selectin ligands establishes a threshold for L-selectin mediated lymphocyte trafficking to peripheral lymph nodes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Howard Hughes Med Inst, Div Cellular & Mol Med, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A68 EP A68 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600337 ER PT J AU Hirahashil, J Xiao, L Saffaripour, S Wagner, DD Shapiro, SD Mayadas, TN AF Hirahashil, J Xiao, L Saffaripour, S Wagner, DD Shapiro, SD Mayadas, TN TI Mac-1 (CD18/CD11b, CR3)-dependent elastase cytotoxicity is required for tissue damage in a model of thrombohemorrhagic vasculitis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Brigham & Womens Hosp, Ctr Excellence Vasc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A389 EP A389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601870 ER PT J AU Jones, RC Jacobson, M Capen, D AF Jones, RC Jacobson, M Capen, D TI Imaging wall structure and PDGF signaling in microvessels in pulmonary hypertension [PH]: quantitative analysis of immunogold labels reveals high PDGF-R beta and restricted PDGF-BB signaling in endothelial cells [ECs] and developing mural cells [MCs] SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A386 EP A386 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601858 ER PT J AU Kogan, AN Robinson, SD Hynes, RO von Andrian, UH AF Kogan, AN Robinson, SD Hynes, RO von Andrian, UH TI An accessory role for P-selectin in lymphocyte homing to peripheral lymph nodes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. MIT, Canc Res Ctr, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A447 EP A447 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602157 ER PT J AU Kucik, DF Ni, N Kevil, CG Bullard, DC AF Kucik, DF Ni, N Kevil, CG Bullard, DC TI Avidity modulation by integrin rearrangement on leukocytes under shear stress SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Birmingham VA Med Ctr, Res Serv, Birmingham, AL 35294 USA. Univ Alabama, Birmingham, AL 35294 USA. Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. RI Kevil, Christopher/G-9318-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A388 EP A388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601866 ER PT J AU Lathers, DMR Young, MRI AF Lathers, DMR Young, MRI TI Analyses of squamous cell carcinoma-recruited T-cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Med Univ S Carolina, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC USA. Ralph H Johnson VA Med Ctr, Res Serv, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A66 EP A66 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600328 ER PT J AU Lee, JA Sinkovits, R Mocks, D Rab, EL Cai, J Yang, P Saunders, B Hsuch, RC Choi, S Roach, TIA Subramaniam, S Scheuermann, RH AF Lee, JA Sinkovits, R Mocks, D Rab, EL Cai, J Yang, P Saunders, B Hsuch, RC Choi, S Roach, TIA Subramaniam, S Scheuermann, RH TI Molecular components of B cell antigen receptor-mediated endocytosis revealed by a tool for functional classification of microarray gene clusters SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Calif San Diego, San Diego Supercomp Ctr, San Diego, CA 92103 USA. AfCS, Dallas, TX USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. San Francisco VAMC, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A51 EP A51 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600253 ER PT J AU Macey, TA Buck, DC Neve, KA AF Macey, TA Buck, DC Neve, KA TI Differences in the interaction of the dopamine D2 receptor and endogenous beta-arrestin1 and 2 in primary striatal cultures and D2 NS20Y cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A588 EP A588 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602821 ER PT J AU Neve, KA Buck, DC Wang, CH AF Neve, KA Buck, DC Wang, CH TI Dopamine D2 receptor-mediated stimulation of mitogen-activated protein kinases by transactivation of receptor tyrosine kinases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A588 EP A588 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602820 ER PT J AU Ranganathan, S Jordan, K Sathanoori, R Henry, SE Day, BW Cudkowicz, ME Brown, RH Bowser, RP AF Ranganathan, S Jordan, K Sathanoori, R Henry, SE Day, BW Cudkowicz, ME Brown, RH Bowser, RP TI Protein profiling of cerebrospinal fluid for ALS specific biomarkers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Pittsburgh, Genom & Proteom Core Facil, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 16066 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A567 EP A567 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602719 ER PT J AU Rossen, RD Trial, J Rubio, JA Birdsall, HH AF Rossen, RD Trial, J Rubio, JA Birdsall, HH TI Monocyte activation by circulating fibronectin fragments in HIV-1 infected patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A89 EP A89 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600438 ER PT J AU Rumbaut, RE Randhawa, JK Burns, AR AF Rumbaut, RE Randhawa, JK Burns, AR TI Endotoxin enhances platelet thrombi formation in mouse cremaster microvessels SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A621 EP A621 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602980 ER PT J AU Tian, J Schmidt-Supprian, M Grant, EP Delaney, T Pasparakis, M Casola, S Gutierrez-Ramos, JC Coyle, AJ Rajewsky, K AF Tian, J Schmidt-Supprian, M Grant, EP Delaney, T Pasparakis, M Casola, S Gutierrez-Ramos, JC Coyle, AJ Rajewsky, K TI The role of IKK beta in CD4+CD25+ T cell and NKT cell development and function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. EMBL Monterotondo, Mouse Biol Programme, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A86 EP A86 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600424 ER PT J AU Wang, JH Yu, SH Liu, C Zhou, JL Liu, ZY Zhang, LM Hsu, HC Mountz, JD Zhang, HG AF Wang, JH Yu, SH Liu, C Zhou, JL Liu, ZY Zhang, LM Hsu, HC Mountz, JD Zhang, HG TI Dysregulation of ubiquitination and phosphorylation of AKT is essential for development of apoptosis resistance in rheumatoid synovial fibroblasts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. Univ Alabama, Vet Adm Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A470 EP A470 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602267 ER PT J AU Yang, PA Hsu, HC Zhang, HG Mountz, JD AF Yang, PA Hsu, HC Zhang, HG Mountz, JD TI Resistance to poxvirus virulence is associated with IL-18 production in genetically diverse strains of mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Alabama, Birmingham, AL 35294 USA. UAB, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A91 EP A91 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600447 ER PT J AU Ingelsson, M Fukumoto, H Newell, KL Growdon, JH Hedley-Whyte, ET Frosch, MP Albert, MS Hyman, BT Irizarry, MC AF Ingelsson, M Fukumoto, H Newell, KL Growdon, JH Hedley-Whyte, ET Frosch, MP Albert, MS Hyman, BT Irizarry, MC TI Early A beta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; SENILE PLAQUES; NEUROFIBRILLARY TANGLES; APOLIPOPROTEIN-E; HIPPOCAMPAL-FORMATION; ENTORHINAL CORTEX; PROTEIN; DEPOSITION; PATHOLOGY; PEPTIDE AB Background: Pathologic changes in the Alzheimer disease ( AD) brain occur in a hierarchical neuroanatomical pattern affecting cortical, subcortical, and limbic regions. Objective: To define the time course of pathologic and biochemical changes - amyloid deposition, amyloid beta-peptide (Abeta) accumulation, neurofibrillary tangle (NFT) formation, synaptic loss, and gliosis - within the temporal association cortex of AD cases of varying disease duration, relative to control brains. Methods: Stereologic assessments of amyloid burden and tangle density as well as ELISA-based measurements of Abeta, synaptophysin, and glial fibrillary acidic protein (GFAP) were performed in the superior temporal sulcus from a cohort of 83 AD and 26 nondemented control brains. Results: Relative to control cases, AD brains were characterized by accumulation of NFT and amyloid plaques, increase of tris- and formic acid - extractable Abeta species, reduced levels of synaptophysin, and elevated levels of GFAP. In AD cases, the duration of dementia correlated with the degree of tangle formation, gliosis, and synaptic loss but not with any Abeta measures. Accumulation of Abeta, measured both neuropathologically and biochemically, was markedly increased in AD brains independent of disease duration, even in cases of short duration. Conclusions: These data support distinct processes in the initiation and progression of AD pathology within the temporal cortex: Deposition of Abeta reaches a "ceiling" early in the disease process, whereas NFT formation, synaptic loss, and gliosis continue throughout the course of the illness. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Alzheimer Dis Res Unit, 114 16 St, Charlestown, MA 02129 USA. EM mirizarry@partners.org FU ACF HHS [AF07370]; NIA NIH HHS [AG04953, AG05134]; NINDS NIH HHS [NS 31862] NR 42 TC 298 Z9 304 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 2004 VL 62 IS 6 BP 925 EP 931 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 805KN UT WOS:000220365300017 PM 15037694 ER PT J AU Brunet, JP Tamayo, P Golub, TR Mesirov, JP AF Brunet, JP Tamayo, P Golub, TR Mesirov, JP TI Metagenes and molecular pattern discovery using matrix factorization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION; MICROARRAY DATA; DECOMPOSITION; PREDICTION AB We describe here the use of nonnegative matrix factorization (NMF), an algorithm based on decomposition by parts that can reduce the dimension of expression data from thousands of genes to a handful of metagenes. Coupled with a model selection mechanism, adapted to work for any stochastic clustering algorithm, NMF is an efficient method for identification of distinct molecular patterns and provides a powerful method for class discovery. We demonstrate the ability of NMF to recover meaningful biological information from cancer-related microarray data. NMF appears to have advantages over other methods such as hierarchical clustering or self-organizing maps. We found it less sensitive to a priori selection of genes or initial conditions and able to detect alternative or context-dependent patterns of gene expression in complex biological systems. This ability, similar to semantic polysemy in text, provides a general method for robust molecular pattern discovery. C1 MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mesirov, JP (reprint author), MIT, Eli & Edythe L Broad Inst, 320 Charles St, Cambridge, MA 02141 USA. EM mesirov@broad.mit.edu NR 15 TC 552 Z9 569 U1 1 U2 23 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 MAR 23 PY 2004 VL 101 IS 12 BP 4164 EP 4169 DI 10.1073/pnas.0308531101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 806ZQ UT WOS:000220472200033 PM 15016911 ER PT J AU Malinski, MK Sesso, HD Lopez-Jimenez, F Buring, JE Gaziano, JM AF Malinski, MK Sesso, HD Lopez-Jimenez, F Buring, JE Gaziano, JM TI Alcohol consumption and cardiovascular disease mortality in hypertensive men SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; U-SHAPED CURVE; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; NUTRITION COMMITTEE; RISK; SMOKING; QUESTIONNAIRE AB Background: Heavy alcohol drinking is associated with a dose-dependent increase in blood pressure, but data on the relation between alcohol consumption and mortality in hypertensive patients are sparse. Objective: To assess the relation between light to moderate alcohol consumption and total mortality from cardiovascular disease (CVD) among men with hypertension. Participants and Design: From the Physicians' Health Study enrollment cohort of 88 882 men who provided self-reported information on alcohol intake, we identified a group of 14 125 men with a history of current or past treatment for hypertension who were free of myocardial infarction, stroke, cancer, or liver disease at baseline. Main Outcome Measure: Comparison of total and CVD mortality among men with hypertension who had reported to be either nondrinkers or rare drinkers, or light to moderate drinkers. Results: During 75 710 person-years of follow-up, there were 1018 deaths, including 579 from CVD. Compared with individuals who rarely or never drank alcoholic beverages, those who reported monthly, weekly, and daily alcohol consumption, respectively, had multivariate adjusted relative risks (RRs) for CVD mortality of 0.83 (95% confidence interval [CI], 0.62-1.13), 0.61 (CI, 0.49-0.77), and 0.56 (CI, 0.44-0.71) (P<.001 for linear trend). In the same groups, RRs for total mortality were respectively 0.86 (CI, 0.67-1.10), 0.72 (CI, 0.60-0.86), and 0.73 (CI, 0.61-0.87) (P<.001 for linear trend). Among men with a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher, the RRs for CVD mortality were, respectively, 1.00 (referent), 0.82 (CI, 0.56-1.21), 0.64 (CI, 0.48-0.85), and 0.56 (CI, 0.42-0.75) (P<.001 for linear trend). On the other hand, we found no significant association between moderate alcohol consumption and cancer mortality (P=.8 for linear trend). Conclusion: These results, which require confirmation in other large-scale studies, suggest that light to moderate alcohol consumption is associated with a reduction in risk of total and CVD mortality in hypertensive men. C1 Mayo Clin & Mayo Fdn, Div Cardiovasc, Rochester, MN 55905 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Prevent Med, Div Prevent Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, St Vincent Hosp, Worcester Med Ctr, Worcester, MA USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Dept Prevent Med, Div Prevent Med, 900 Commonwealth E Ave, Boston, MA 02115 USA. EM jgaziano@partners.org FU NCI NIH HHS [R01 CA097193]; NHLBI NIH HHS [HL/42441] NR 41 TC 50 Z9 51 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 22 PY 2004 VL 164 IS 6 BP 623 EP 628 DI 10.1001/archinte.164.6.623 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 804QQ UT WOS:000220313600006 PM 15037490 ER PT J AU Peng, CC Glassman, PA Trilli, LE Hayes-Hunter, J Good, CB AF Peng, CC Glassman, PA Trilli, LE Hayes-Hunter, J Good, CB TI Incidence and severity of potential drug-dietary supplement interactions in primary care patients - An exploratory study of 2 outpatient practices SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; SAFETY ISSUES; HEALTH; MEDICINE; HYPERKALEMIA; POPULATION; REMEDIES; PATTERNS; PRODUCTS; WARFARIN AB Background: To explore the incidence and severity of potential interactions between prescription medications and dietary supplements. Methods: A survey was conducted on dietary supplement use in 458 veteran outpatients currently taking prescription medications. Self-reported dietary supplement use was cross-referenced with each patient's prescription medication list, and potential interactions were identified from several tertiary sources and medical literature searches. Results: One hundred ninety-seven patients (43%) were currently taking at least I dietary supplement with prescription medication(s). The most common products included vitamins and minerals, garlic, Ginkgo biloba, saw palmetto, and ginseng. Among these, 89 (45%) had a potential for drug-dietary supplement interactions of any significance. Most of these interactions (n=84 [94%]) were not serious based on limited available evidence, giving an incidence of 6% (5/89) of potentially severe interactions among patients taking interacting drugs and dietary supplements and 3% (5/197) among patients taking coincident dietary supplements and medications. Conclusions: Although the use of dietary supplements appears to be very common among patients who also take prescription medications, most potential drug-dietary supplement interactions found were not serious. However, literature support was sparse at best. Health care providers should continue to inquire about dietary supplement use and consider the potential for interactions, regardless of their severity. C1 Univ So Calif, Sch Pharm, Dept Pharm, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Pittsburgh, Sch Med, Dept Med & Pharm, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Div Gen Internal Med, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Serv Pharm, Pittsburgh, PA USA. RP Glassman, PA (reprint author), Vet Affairs Greater Los Angeles W Los Angeles, Div Gen Internal Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Peter.glassman@med.va.gov NR 41 TC 61 Z9 67 U1 5 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 22 PY 2004 VL 164 IS 6 BP 630 EP 636 DI 10.1001/archinte.164.6.630 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 804QQ UT WOS:000220313600007 PM 15037491 ER PT J AU Paganetti, H AF Paganetti, H TI Four-dimensional Monte Carlo simulation of time-dependent geometries SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOTHERAPY AB Dynamic radiation therapy techniques require that the treatment head setup varies in time and space during dose delivery. Examples are leaf motion in intensity modulated x-ray therapy, modulator wheel rotation in conventional proton therapy and variable magnet settings in proton beam scanning. Consequently, for Monte Carlo dose calculation the results of several independent simulations usually have to be combined. Depending on the complexity and the required accuracy this can become cumbersome. We present a technique to simulate time-dependent geometries within a single four-dimensional Monte Carlo simulation using the GEANT4 Monte Carlo package. Results for proton therapy applications are shown. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hpaganetti@partners.org FU NCI NIH HHS [CA 21239] NR 11 TC 38 Z9 38 U1 3 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 21 PY 2004 VL 49 IS 6 BP N75 EP N81 AR PII S0031-9155(04)72480-X DI 10.1088/0031-9155/49/6/N03 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 809PU UT WOS:000220649400018 PM 15104330 ER PT J AU Chang, JT Morton, SC Rubenstein, LZ Mojica, WA Maglione, M Suttorp, MJ Roth, EA Shekelle, PG AF Chang, JT Morton, SC Rubenstein, LZ Mojica, WA Maglione, M Suttorp, MJ Roth, EA Shekelle, PG TI Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials SO BRITISH MEDICAL JOURNAL LA English DT Article ID NURSING-HOME RESIDENTS; RISK-FACTORS; MULTIFACTORIAL INTERVENTION; ELDERLY-PATIENTS; COMMUNITY; PEOPLE; BALANCE; FRAILTY; QUALITY; INJURY AB Objective To assess the relative effectiveness of interventions to prevent falls in older adults to either a usual care group or control group. Design Systematic review and meta-analyses. Data sources Medline, HealthSTAR, Embase, the Cochrane Library, other health related databases, and the reference lists from review articles and systematic reviews. Data extraction Components of falls intervention: multifactorial falls risk assessment with management programme, exercise, environmental modifications, or education. Results 40 trials were identified. A random effects analysis combining trials with risk ratio data showed a reduction in the risk of falling (risk ratio 0.88, 95% confidence interval 0.82 to 0.95), whereas combining trials with incidence rate data showed a reduction in the monthly rate of failing (incidence rate ratio 0.80, 0.72 to 0.88). The effect of individual components was assessed by meta-regression. A multifactorial falls risk assessment and management programme was the most effective component on risk of falling (0.82,0.72 to 0.94, number needed to treat 11) and monthly fall rate (0.63, 0.49 to 0.83; 11.8 fewer falls in treatment group per 100 patients per month). Exercise interventions also had a beneficial effect on the risk of falling (0.86, 0.75 to 0.99, number needed to treat 16) and monthly fall rate (0.86, 0.73 to 1.01; 2.7). Conclusions Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. RAND Corp, Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90407 USA. Greater Los Angeles VA Med Ctr, Sepulveda, CA 91343 USA. RP Chang, JT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Ave, Los Angeles, CA 90095 USA. EM johnchang@mednet.ucla.edu FU BHP HRSA HHS [PE-19001] NR 40 TC 504 Z9 531 U1 13 U2 72 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAR 20 PY 2004 VL 328 IS 7441 BP 680 EP 683 DI 10.1136/bmj.328.7441.680 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 805VB UT WOS:000220392700019 PM 15031239 ER PT J AU Tang, W Hemler, ME AF Tang, W Hemler, ME TI Caveolin-1 regulates matrix metalloproteinases-1 induction and CD147/EMMPRIN cell surface clustering SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLLAGENASE-STIMULATORY FACTOR; IMMUNOGLOBULIN SUPERFAMILY; LIPID RAFTS; EXPRESSION; INTEGRIN; TUMOR; CD147; INDUCER; BASIGIN; EMMPRIN AB CD147, a regulator of matrix metalloproteinase (MMP) production, showed highly specific association with caveolin-1 on the surface of multiple cell types. CD147-caveolin-1 complex formation was temperature and cholesterol dependent, reminiscent of associations seen within caveolae/lipid rafts. However, the subset of caveolin-1 associated with CD147 appeared exclusively within intermediate density sucrose gradient fractions, rather than in the low density fractions containing the bulk of caveolin-1. Mutagenesis experiments revealed that CD147 Ig domain 2 was required for caveolin-1 association. In contrast to CD147-caveolin-1 complexes, CD147-alpha(3) integrin association was not disrupted upon cholesterol depletion, occurred in high density sucrose fractions, and did not involve CD147 Ig domain 2. Overexpression of caveolin-1 caused a specific decrease in clustering of cell surface CD147, as detected by "cluster specific" mAb M6/13. Conversely, a mutant CD147 deficient in caveolin-1 association showed enhanced spontaneous cell surface clustering ( detected by mAb M6/13), and did not show decreased clustering in response to caveolin-1 overexpression. Furthermore, the same CD147 mutant yielded an elevated induction of MMP-1. In conclusion, caveolin-1 associates with CD147, in a complex distinct from CD147-alpha(3) integrin complexes, thereby diminishing both CD147 clustering and CD147-dependent MMP-1-inducing activity. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@dfci.harvard.edu FU NCI NIH HHS [CA86712] NR 51 TC 106 Z9 115 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 MAR 19 PY 2004 VL 279 IS 12 BP 11112 EP 11118 DI 10.1074/jbc.M312947200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802IQ UT WOS:000220157600035 PM 14707126 ER PT J AU Chang, JD Field, SJ Rameh, LE Carpenter, CL Cantley, LC AF Chang, JD Field, SJ Rameh, LE Carpenter, CL Cantley, LC TI Identification and characterization of a phosphoinositide phosphate kinase homolog SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASES; PROTEIN; FAMILY; MYOTUBULARIN; VESICLES; ALPHA; 3-PHOSPHATASE; REGULATORS; MOVEMENT; PATHWAY AB Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P-2) plays a central role in regulating the actin cytoskeleton as a substrate for phosphoinositide 3-kinase and phospholipase C as well as by binding directly to proteins that control the processes of actin monomer sequestration, filament severing, capping, nucleation, cross-linking, and bundling (Ma, L., Cantley, L. C., Janmey, P. A., and Kirschner, M. W. (1998) J. Cell Biol. 140, 1125 1136; Hinchliffe, K. (2000) Curr. Biol. 10, R104-R1051). Three related phosphatidylinositol 4-phosphate 5-kinases (PI(4)P 5-kinases) have been identified in mammalian cells (types Ialpha, Ibeta, and Igamma) and appear to play distinct roles in actin remodeling. Here we have identified a fourth member of this family by searching the human genome and EST data bases. This new protein, which we have designated phosphatidylinositol phosphate kinase homolog (PIPKH), is expressed at relatively high levels in brain and testis. Immunoprecipitates of PIPKH expressed in mammalian cells contain PI(4)P 5-kinase activity, but this activity is not affected by mutations in residues that inactivate other type I PI(4)P 5-kinases. We show that the PI(4)P 5-kinase activity in PIPKH immunoprecipitates can be explained by the ability of PIPKH to heterodimerize with other type I PI(4)P 5-kinases. Transfection of 293t cells with PIPKH resulted in >8-fold increase in total phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P-3) without a significant net increase in total PI(4,5)P-2. When coexpressed with PIPKH, green fluorescent protein (GFP) fusion construct of the pleckstrin homology domain from Bruton's tyrosine kinase (GFP-BTK-PH) localized in intracellular vesicular structures, suggesting an unusual intracellular site of PI(3,4,5)P-3 production. Finally, expression of PIPKH induced the reorganization of actin from predominantly stress fibers to predominantly foci and comets similar to those observed previously in cells infected with the intracellular pathogen Listeria or transfected with recombinant PIPKIalpha. These results suggest that PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P-3. C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Boston Biomed Res Inst, Watertown, MA 02472 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. EM jchang@bidmc.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NHLBI NIH HHS [HL03313]; NIGMS NIH HHS [GM36624, GM54389] NR 31 TC 10 Z9 12 U1 0 U2 0 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 MAR 19 PY 2004 VL 279 IS 12 BP 11672 EP 11679 DI 10.1074/jbc.M309721200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802IQ UT WOS:000220157600102 PM 14701839 ER PT J AU Dobbins, IG Schnyer, DM Verfaellie, M Schacter, DL AF Dobbins, IG Schnyer, DM Verfaellie, M Schacter, DL TI Cortical activity reductions during repetition priming can result from rapid response learning SO NATURE LA English DT Article ID INFERIOR PREFRONTAL CORTEX; FUSIFORM CORTEX; IMPLICIT MEMORY; FUNCTIONAL MRI; MECHANISMS; SPECIFICITY; RETRIEVAL; BRAIN; TASKS AB Recent observation of objects speeds up their subsequent identification and classification(1,2). This common form of learning, known as repetition priming, can operate in the absence of explicit memory for earlier experiences(3,4), and functional neuroimaging has shown that object classification improved in this way is accompanied by 'neural priming' ( reduced neural activity) in prefrontal, fusiform and other cortical regions(5-10). These observations have led to suggestions that cortical representations of items undergo 'tuning', whereby neurons encoding irrelevant information respond less as a given object is observed repeatedly(10), thereby facilitating future availability of pertinent object knowledge. Here we provide experimental support for an alternative hypothesis, in which reduced cortical activity occurs because subjects rapidly learn their previous responses(11). After a primed object classification ( such as 'bigger than a shoebox'), cue reversal ('smaller than a shoebox') greatly slowed performance and completely eliminated neural priming in fusiform cortex, which suggests that these cortical item representations were no more available for primed objects than they were for new objects. In contrast, prefrontal cortex activity tracked behavioural priming and predicted the degree to which cue reversal would slow down object classification - highlighting the role of the prefrontal cortex in executive control. C1 Duke Univ, Durham, NC 27708 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02118 USA. MGH MIT HMS, Athinoua A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Dobbins, IG (reprint author), Duke Univ, Durham, NC 27708 USA. EM ian.dobbins@duke.edu OI Schacter, Daniel/0000-0002-2460-6061; Verfaellie, Mieke/0000-0001-5535-4584 NR 25 TC 190 Z9 193 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 18 PY 2004 VL 428 IS 6980 BP 316 EP 319 DI 10.1038/nature02400 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 803SG UT WOS:000220250200043 PM 14990968 ER PT J AU Garkavtsev, I Kozin, SV Chernova, O Xu, L Winkler, F Brown, E Barnett, GH Jain, RK AF Garkavtsev, I Kozin, SV Chernova, O Xu, L Winkler, F Brown, E Barnett, GH Jain, RK TI The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis SO NATURE LA English DT Article ID INTERLEUKIN-8 EXPRESSION; P53 EXPRESSION; P33(ING1); CANCER; GLIOBLASTOMA; CELLS; FIBROBLASTS; ACTIVATION; INHIBITOR; CARCINOMA AB Gliomas are the most common primary tumours of the central nervous system, with nearly 15,000 diagnosed annually in the United States and a lethality approaching 80% within the first year of glioblastoma diagnosis(1). The marked induction of angiogenesis in glioblastomas suggests that it is a necessary part of malignant progression(2); however, the precise molecular mechanisms underlying the regulation of brain tumour growth and angiogenesis remain unresolved. Here we report that a candidate tumour suppressor gene, ING4, is involved in regulating brain tumour growth and angiogenesis. Expression of ING4 is significantly reduced in gliomas as compared with normal human brain tissue, and the extent of reduction correlates with the progression from lower to higher grades of tumours. In mice, xenografts of human glioblastoma U87MG, which has decreased expression of ING4, grow significantly faster and have higher vascular volume fractions than control tumours. We show that ING4 physically interacts with p65 ( RelA) subunit of nuclear factor NF-kappaB, and that ING4 regulates brain tumour angiogenesis through transcriptional repression of NF-kappaB-responsive genes. These results indicate that ING4 has an important role in brain tumour pathogenesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiat Oncol, Edwin L Steele Lab Tumour Biol, Boston, MA 02114 USA. Cleveland Clin Fdn, Brain Tumour Inst, Cleveland, OH 44195 USA. RP Garkavtsev, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiat Oncol, Edwin L Steele Lab Tumour Biol, Boston, MA 02114 USA. EM igorg@steele.mgh.harvard.edu NR 25 TC 238 Z9 281 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 18 PY 2004 VL 428 IS 6980 BP 328 EP 332 DI 10.1038/nature02329 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 803SG UT WOS:000220250200046 PM 15029197 ER PT J AU Schnitzer, JJ Briggs, SM AF Schnitzer, JJ Briggs, SM TI Earthquake relief - The US medical response in Bam, Iran SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Int Med Surg Response Team, Boston, MA USA. RP Schnitzer, JJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 2 TC 21 Z9 22 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAR 18 PY 2004 VL 350 IS 12 BP 1174 EP 1176 DI 10.1056/NEJMp048019 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 803PG UT WOS:000220242400003 PM 15028821 ER PT J AU Gerberding, JL Morgan, JG Shepard, JO Kradin, RL AF Gerberding, JL Morgan, JG Shepard, JO Kradin, RL TI An 18-year-old man with respiratory symptoms and shock - Influenza A infection with rhabdomyolysis, severe; myoglobinuria; viral tracheobronchitis and pneumonia; virus-associated cardiac changes ("borderline myocarditis") and catecholamine-induced myonecrosis; pericardial effusion. Disseminated intravascular coagulation. Hepatic centrilobular necrosis. Cardiac hypertrophy of unknown cause. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACUTE-RENAL-FAILURE; MYOPERICARDITIS; DISEASE; CHILD C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Cardiac Echo Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Gerberding, JL (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 39 TC 9 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAR 18 PY 2004 VL 350 IS 12 BP 1236 EP 1247 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 803PG UT WOS:000220242400012 PM 15028828 ER PT J AU Riley, DE Krieger, JN AF Riley, DE Krieger, JN TI Simple repeat replacements support similar functions of distinct repeats in inter-species mRNA homologs SO GENE LA English DT Article DE short tandem repeats; STRs; UTRs; aquaporin; biglycan; Igsf-9; Tnfr-21 ID SHORT TANDEM REPEATS; SECONDARY STRUCTURE; PROTEIN; GENE; PREDICTION; SEQUENCES; DISEASE; EXPRESSION; EXPANSION; EVOLUTION AB Simple repeats are ubiquitous in metazoan genomes, but function has been elusive. We reported that distinct, short tandem repeats (STRs) were coupled with rigorous polarity and register, suggesting order in simple repeat usage. Several STRs that lacked internal, canonical base pairs were associated with mRNAs encoding membrane functions and transcription factors. We hypothesized that diverse, simple repeats, such as (AC)n, (GU)n, (AG)n, (CU)n and (CUUU)n, had similar functions. The hypothesis predicts that closely related mRNAs would sometimes exhibit STR replacements. Comparing aquaporin 3 mRNAs, in rodents and humans, (GU)20 replaced (AG)29. Comparing biglycan mRNAs, (GU)25 replaced (CA)12. Comparing immunoglobulin superfamily member 9 mRNAs, the STR-couple, (CU)17 (GU)9 replaced the STR-couple, (GU)19 (GC)4. Comparing tumor necrosis factor receptor-21 mRNAs, (GU)24 replaced (CUUU)16. In a collection of 52 rodent-H. sapiens homologous mRNAs that had STRs, six (11.5%) STR-STR replacements occurred, significantly more than expected based on an STR frequency of 0.13% in all reported UTRs (p < 0.001). Database studies and the observation of STR replacements among transcript homologs independently support the hypothesis that diverse repeat sequences, such as (AG)n, (AC)n, (GU)n, (CU)n and (CUUU)n, have similar usage that is consistent with analogous functions. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Vet Affairs Med Ctr, Dept Res 151, Seattle, WA 98012 USA. RP Riley, DE (reprint author), VA Puget Sound Hlth Care Syst, Vet Affairs Med Ctr, Dept Res 151, Room 517,Bldg 1,1660 S Columbian Way, Seattle, WA 98012 USA. EM dri@u.washington.edu FU NIDDK NIH HHS [R01 DK38955] NR 31 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 17 PY 2004 VL 328 BP 17 EP 24 DI 10.1016/j.gene.2003.12.036 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 807YS UT WOS:000220537400002 PM 15019980 ER PT J AU Wu, LZ Kobayashi, K Sun, T Gao, P Liu, JX Nakamura, M Weisberg, E Mukhopadhyay, NK Griffin, JD AF Wu, LZ Kobayashi, K Sun, T Gao, P Liu, JX Nakamura, M Weisberg, E Mukhopadhyay, NK Griffin, JD TI Cloning and functional characterization of the murine mastermind-like 1 (Maml1) gene SO GENE LA English DT Article DE notch signaling; mastermind; transcriptional co-activator ID NOTCH SIGNAL-TRANSDUCTION; TRANSCRIPTIONAL COACTIVATOR; DROSOPHILA MASTERMIND; MAMMALIAN NOTCH; COMPLEX; PATHWAY; PROTEIN; ACTIVATOR; RECEPTORS; BINDING AB The Notch signaling pathway controls cell fate decisions and plays a critical role in normal development and diseases. The human mastermind-like (MAML) family members (MAML 1, 2 and 3) encode critical transcriptional co-activators for Notch receptors. In this study, we cloned a murine cDNA that is highly homologous to the human MAML1 gene, Mam11. Mouse Mam11 encodes a nuclear protein, binds to the ankyrin repeat domain of Notch receptors, forms a ternary complex with the intracellular domain of Notch (ICN) and the DNA binding protein CSL, and enhances Notch-induced transcription of the target gene, HES-1. Therefore, Mam11 is the murine homologue for human MAML1 and functions as a transcriptional co-activator for Notch signaling. We also characterized the organization of the mouse Mam11 gene: It spans at least 35 kilobases (kb) on chromosome 11 and contains five exons and four introns. Analysis of the 5' flanking region revealed that the promoter is TATA-less, and contains consensus binding sites for transcription factors such as Sp1, glucocorticoid receptor (GR), activating transcription factor (ATF) and cAMP response element-binding protein (CREB). Moreover, we examined Mam11 expression during early mouse development and found that Mam11 gene is expressed widely but selectively in several tissues. There seems to be close correlation of the spatial and temporal expression among Mam11, Notch1 and Hes1 in the central nervous system (CNS) during early development, implicating a role for the Mam11 gene in neurogenesis. (C) 2004 Elsevier B.V. All rights reserved. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Inst Med, Sch Med, Beth Israel Deaconess Med Ctr,Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Wu, LZ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Mayer 540,44 Binney St, Boston, MA 02115 USA. EM lizi_wu@dfci.harvard.edu FU NCI NIH HHS [R01 CA036167, R01 CA097148] NR 38 TC 10 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 17 PY 2004 VL 328 BP 153 EP 165 DI 10.1016/j.gene.2003.12.007 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 807YS UT WOS:000220537400017 PM 15019995 ER PT J AU Heidenreich, PA Gubens, MA Fonarow, GC Konstam, MA Stevenson, LW Shekelle, PG AF Heidenreich, PA Gubens, MA Fonarow, GC Konstam, MA Stevenson, LW Shekelle, PG TI Cost-effectiveness of screening with B-type natriuretic peptide to identify patients with reduced left ventricular ejection fraction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; SYSTOLIC DYSFUNCTION; CLINICAL-TRIALS; PREVALENCE; MANAGEMENT; POPULATION; ENALAPRIL; COMMUNITY; MORTALITY; METAANALYSIS AB OBJECTIVES This study was designed to evaluate the cost-effectiveness of screening patients with a B-type natriuretic peptide (BNP) blood test to identify those with depressed left ventricular systolic function. BACKGROUND Asymptomatic patients with depressed ejection fraction (EF) may have less progression to heart failure if they can be identified and treated. METHODS We used a decision model to estimate economic and health outcomes for different screening strategies using BNP and echocardiography to detect left ventricular EF <40% for men and women age 60 years. We used published data from community cohorts (gender-specific BNP test characteristics, prevalence of depressed EF) and randomized trials (benefit from treatment). RESULTS Screening 1,000 asymptomatic patients with BNP followed by echocardiography in those with an abnormal test increased the lifetime cost of care ($176,000 for men, $101,000 for women) and improved outcome (7.9 quality- adjusted life years [QALYs] for men, 1.3 QALYs for women), resulting in a cost per QALY of $22,300 for men and $77,700 for women. For populations with a prevalence of depressed EF of at least 1%, screening with BNP followed by echocardiography increased outcome at a cost <$50,000 per QALY gained. Screening would not be attractive if a diagnosis of left ventricular dysfunction led to significant decreases in quality of life or income. CONCLUSIONS Screening populations with a 1% prevalence of reduced EF (men at age 60 years) with BNP followed by echocardiography should provide a health benefit at a cost that is comparable to or less than other accepted health interventions. (C) 2004 by the American College of Cardiology Foundation. C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufs New England Med Ctr, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Heidenreich, PA (reprint author), VAMC, 111C Cardiol,3801 Miranda Ave, Palo Alto, CA 94034 USA. EM heiden@stanford.edu OI Heidenreich, Paul/0000-0001-7730-8490 NR 34 TC 115 Z9 120 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2004 VL 43 IS 6 BP 1019 EP 1026 DI 10.1016/j.jacc.2003.10.043 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803DS UT WOS:000220212400016 PM 15028361 ER PT J AU Wu, SS Zhou, LQ Rose, M Xiao, X Graham, SH AF Wu, SS Zhou, LQ Rose, M Xiao, X Graham, SH TI c-FLIP-L recombinant adeno-associated virus vector infection prevents Fas-mediated but not nerve growth factor withdrawal-mediated cell death in PC12 cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE c-FLIP-L; caspase 8; rAAV; Fas; NGF withdrawal; FADD ID DOMAIN-CONTAINING PROTEIN; SIGNALING COMPLEX DISC; SYMPATHETIC NEURONS; INHIBITORY PROTEIN; CD95-MEDIATED APOPTOSIS; CASPASE-8 ACTIVATION; GENE-TRANSFER; EXPRESSION; RECEPTOR; CD95 AB Fas is a cell surface death receptor that may play an important role in regulating cell death in neuronal cell types by activation of caspase 8. Cellular FLICE inhibitory protein-long (c-FLIP-L) is an endogenous inhibitor of the activation of caspase 8 by Fas. The current study addresses the role of c-FLIP-L in regulation of cell death in PC12 cells induced by nerve growth factor (NGF) withdrawal and Fas antibody, which acts as a Fas ligand and activates the Fas receptor. A recombinant adeno-associated virus (rAAV) vector that expresses c-FLIP-L was constructed. PC12 cells infected with the c-FLIP-L rAAV were resistant to apoptosis induced by treatment with Fas antibody compared to cells infected with enhanced green fluorescent protein (EGFP) expressing rAAV. Overexpression of c-FLIP-L rAAV inhibited cleavage of caspase 8 induced by Fas antibody treatment. In contrast, treatment with the c-FLIP-L rAAV did not protect PC12 cells from cell death induced by NGF withdrawal. In conclusion, overexpression of c-FLIP-L rAAV inhibits Fas antibody-mediated cell death, but not NGF withdrawal-mediated cell death in PC12 cells. Published by Elsevier B.V. C1 VA Pittsburgh Hlth Syst, ACOS RD, Res Serv 151, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. RP Graham, SH (reprint author), VA Pittsburgh Hlth Syst, ACOS RD, Res Serv 151, Geriatr Res Educ & Clin Ctr, Univ Dr C, Pittsburgh, PA 15240 USA. EM sgra@pitt.edu NR 52 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAR 17 PY 2004 VL 122 IS 1 BP 79 EP 87 DI 10.1016/j.molbrainres.2003.12.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 804BD UT WOS:000220273300009 ER PT J AU Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM O'Donnell, CJ Wilson, PWF AF Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM O'Donnell, CJ Wilson, PWF TI Accuracy of offspring reports of parental cardiovascular disease history: The Framingham offspring study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; HIGH BLOOD CHOLESTEROL; FAMILY-HISTORY; MYOCARDIAL-INFARCTION; RISK FACTOR; ARTERY DISEASE; HYPERTENSION; STROKE; MEN AB Background: Family history is used to infer the risk for heart disease; however, little is known about the accuracy of family history reports. Objective: To examine the accuracy of offspring reports of parental cardiovascular disease. Design: Validation study. Setting: Framingham Heart Study. Participants: Offspring participants of the multigenerational Framingham Heart Study with both parents in the original cohort. Measurements: 791 men and 837 women (mean age, 57 years) completed a family history questionnaire from 1995 to 1998. Offspring reports were compared with confirmed medical evidence of parental status, and positive and negative predictive values and likelihood ratios were calculated. Results: Positive reports of high blood pressure, diabetes, and high cholesterol levels in fathers were accurate: Positive predictive values were 83% (95% CI, 80% to 86%), 76% (CI, 70% to 82%), and 78% (CI, 73% to 83%), respectively. Corresponding positive predictive values for reports in mothers were 91% (Cl, 89% to 93%), 79% (CI, 73% to 85%), and 88% (CI, 84% to 92%), respectively. Positive predictive values for reports of paternal heart attack occurring before 55 years of age and for stroke occurring before 65 years of age were 28% (CI, 22% to 34%) and 43% (CI, 33% to 53%), respectively, whereas the positive likelihood ratios were 8.6 (CI, 6.8 to 10.9) and 11.2 (CI, 9.2 to 13.6), respectively. Negative predictive values for parental history reports were greater than 90%, except for high blood pressure and high cholesterol level (negative predictive values, 33% to 55%, and negative likelihood ratios, 0.47 to 0.88). Limitations: This study does not determine whether more accurate measures of family history would meaningfully improve estimation of cardiovascular risk. Conclusions: Negative parental history reports were reliable, except for hypertension and high cholesterol levels. Although reports of parental premature heart attack and stroke had high likelihood ratios, their predictive values were low because the prevalence of these conditions was low in parents. If patients were more aware of their parents' medical illnesses, they might be able to estimate their risk for disease more accurately and perhaps motivate themselves to follow a healthy lifestye. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Massachusetts Gen Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Joanne@fram.nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-25195] NR 30 TC 115 Z9 116 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 2004 VL 140 IS 6 BP 434 EP 440 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 803AU UT WOS:000220204800004 PM 15023709 ER PT J AU Woolf, CJ AF Woolf, CJ TI Pain: Moving from symptom control toward mechanism-specific pharmacologic management SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RAT SENSORY NEURONS; NERVE INJURY; SPINAL-CORD; CENTRAL SENSITIZATION; MOLECULAR-MECHANISMS; NEUROPATHIC PAIN; MYELINATED AFFERENTS; SODIUM-CHANNELS; PROTEIN-KINASE; UP-REGULATION C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, 149 13th St,Room 4309, Boston, MA 02129 USA. EM cwoolf@partners.org NR 45 TC 344 Z9 356 U1 3 U2 28 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 2004 VL 140 IS 6 BP 441 EP 451 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 803AU UT WOS:000220204800005 PM 15023710 ER PT J AU Smetana, GW Cohn, SL Lawrence, VA AF Smetana, GW Cohn, SL Lawrence, VA TI Update in perioperative medicine SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID POSTOPERATIVE PULMONARY COMPLICATIONS; MAJOR NONCARDIAC SURGERY; CARDIAC RISK; MYOCARDIAL-INFARCTION; VASCULAR-SURGERY; DISEASE; SMOKING; INDEX C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. SUNY Hlth Sci Ctr, Med Ctr, Brooklyn, NY USA. S Texas Vet Hlth Care Syst, VERDICT, San Antonio, TX USA. Univ Texas, Ctr Hlth, San Antonio, TX 78285 USA. RP Smetana, GW (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Shapiro 621D,330 Brookline Ave, Boston, MA 02215 USA. NR 18 TC 9 Z9 10 U1 1 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 2004 VL 140 IS 6 BP 452 EP 461 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 803AU UT WOS:000220204800006 PM 15023711 ER PT J AU Zhang, M Austen, WG Chiu, I Alicot, EM Hung, R Ma, MH Verna, N Xu, M Hechtman, HB Moore, FD Carroll, MC AF Zhang, M Austen, WG Chiu, I Alicot, EM Hung, R Ma, MH Verna, N Xu, M Hechtman, HB Moore, FD Carroll, MC TI Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; COMPLEMENT RECEPTOR TYPE-1; NATURAL ANTIBODY; SKELETAL-MUSCLE; TRANSGENIC MICE; LUNG INJURY; MAST-CELLS; B-CELLS; B-1; NEUTROPHIL AB Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of lgM-producing hybridomas prepared from peritoneal cells enriched in B-1 cells. One clone, CM22, was identified that could restore pathogenic injury in RAG-1(-/-) mice in an intestinal model of ischemia/reperfusion (I/R). In situ activation of the classical pathway of complement was evident by deposition of IgM, complement C4, and C3 in damaged tissue after passive transfer of CM22 IgM. Sequence analysis of CM22 Ig heavy and light chains showed germ-line configurations with high homology to a V-H sequence from the B-1 repertoire and a V-K of a known polyreactive natural IgM. These data provide definitive evidence that I/R injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. This finding opens an avenue for identification of I/R-specific self-antigen(s) and early prevention of injury. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Nat Antibodies Inc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu FU NIAID NIH HHS [R43-AI51045-01A1, R43 AI051045]; NIGMS NIH HHS [P50 GM052585, P01-GM52585] NR 32 TC 143 Z9 150 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 MAR 16 PY 2004 VL 101 IS 11 BP 3886 EP 3891 DI 10.1073/pnas.0400347101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804QZ UT WOS:000220314500032 PM 14999103 ER PT J AU Castigli, E Scott, S Dedeoglu, F Bryce, P Jabara, H Bhan, AK Mizoguchi, E Geha, RS AF Castigli, E Scott, S Dedeoglu, F Bryce, P Jabara, H Bhan, AK Mizoguchi, E Geha, RS TI Impaired IgA class switching in APRIL-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NECROSIS-FACTOR FAMILY; B-CELL MATURATION; FACTOR RECEPTOR SUPERFAMILY; LYMPHOCYTE STIMULATOR; AUTOIMMUNE-DISEASE; TNF RECEPTOR; CD40-DEFICIENT MICE; INTESTINAL IGA; MEMBERS BAFF; BCMA GENE AB The tumor necrosis factor (TNF) family member APRIL binds to the receptors BCMA on B cells and TACI on B and T cells. To investigate the role of APRIL in immunity, we generated APRIL-deficient mice. APRIL(-'-) mice have normal T and B lymphocyte development, normal T and B cell proliferation in vitro, but increased numbers of CD44(hi)CD62L(lo) CD4(+) effector/memory T cells and increased IgG responses to T-dependent antigens. Serum IgA levels were significantly decreased, and serum IgA antibody responses to mucosal immunization with TD antigens and to type 1 T-independent antigens were impaired in APRIL(-/-) mice. APRIL by itself induced IgA as well as IgG1 isotype switching in CD40-deficient IgM(+)IgD(+) sorted B cells. These results suggest that APRIL down-regulates T cell-dependent antibody responses and promotes IgA class switching. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Immunopathol Unit, Boston, MA 02115 USA. RP Geha, RS (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. EM raif.geha@tch.harvard.edu FU NIAID NIH HHS [P01 AI031541, AI31136, AI31541, R01 AI031136, U19 AI031541]; NIDDK NIH HHS [DK43351, DK47677, P30 DK043351, R01 DK047677] NR 42 TC 255 Z9 265 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 MAR 16 PY 2004 VL 101 IS 11 BP 3903 EP 3908 DI 10.1073/pnas.0307348101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804QZ UT WOS:000220314500035 PM 14988498 ER PT J AU Chen, HL Zhang, SMM Schwarzschild, MA Hernan, MA Willett, WC Ascherio, A AF Chen, HL Zhang, SMM Schwarzschild, MA Hernan, MA Willett, WC Ascherio, A TI Obesity and the risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body composition; body mass index; obesity; Parkinson disease; prospective studies ID CORONARY-HEART-DISEASE; CLINICAL-DIAGNOSIS; FAT DISTRIBUTION; NURSES HEALTH; TOBACCO-SMOKE; FOOD-INTAKE; BODY-SIZE; ACCURACY; DOPAMINE; WOMEN AB Dopamine is involved in the regulation of food intake, and obese persons have decreased dopamine D2 receptor availability in the striatum. Furthermore, midlife triceps skinfold thickness has been found to be positively associated with the risk of Parkinson's disease (PD) among Japanese-American men in Hawaii. The authors prospectively investigated whether obesity was associated with PD risk in two large cohorts of US men and women. They documented 249 cases of PD in men (1986-2000) and 202 cases in women (1976-1998). Neither baseline body mass index (weight (kg)/height (m)(2)) nor early adult body mass index was associated with PD risk. The multivariate relative risk for a baseline body mass index of greater than or equal to30 versus <23 was 0.8 (95% confidence interval (CI): 0.6, 1.2; p for trend = 0.3). Overall, waist circumference and waist-to-hip ratio were not related to PD risk. However, among never smokers, both variables showed significantly positive associations with PD risk. The relative risks for comparisons of extreme quintiles were 1.9 (95% CI: 1.0, 3.4; p for trend = 0.03) for waist circumference and 2.0 (95% CI: 1.1, 3.6; p for trend = 0.03) for waist-to-hip ratio. The results do not support a role of overall obesity in PD pathogenesis; however, central obesity may be associated with higher PD risk among never smokers, and this finding merits further investigation. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Chen, HL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM hchen@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NCI NIH HHS [CA 87969]; NINDS NIH HHS [NS 35624] NR 41 TC 48 Z9 48 U1 1 U2 7 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 MAR 15 PY 2004 VL 159 IS 6 BP 547 EP 555 DI 10.1093/aje/kwh059 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 802RM UT WOS:000220180600003 PM 15003958 ER PT J AU Simon, JA Murtaugh, MA Gross, MD Loria, CM Hulley, SB Jacobs, DR AF Simon, JA Murtaugh, MA Gross, MD Loria, CM Hulley, SB Jacobs, DR TI Relation of ascorbic acid to coronary artery calcium - The Coronary Artery Risk Development in Young Adults Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antioxidants; ascorbic acid; calcium; cardiovascular diseases ID CARDIOVASCULAR-DISEASE PREVALENCE; LOW-DENSITY-LIPOPROTEIN; VITAMIN-E CONSUMPTION; HEART-DISEASE; US ADULTS; PROSPECTIVE POPULATION; MYOCARDIAL-INFARCTION; PLASMA-CONCENTRATIONS; ANTIOXIDANT VITAMINS; POSTMENOPAUSAL WOMEN AB Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18-30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women. C1 Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Oslo, Inst Nutr Res, Oslo, Norway. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM jasimon@itsa.ucsf.edu OI Murtaugh, Maureen/0000-0001-5281-0302 FU NHLBI NIH HHS [HC 48047, HC 48048, HC 48049, HC 48050, HL 53359] NR 37 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 MAR 15 PY 2004 VL 159 IS 6 BP 581 EP 588 DI 10.1093/aje/kwh079 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 802RM UT WOS:000220180600007 PM 15003962 ER PT J AU Subramanian, U Filn, SD Weinberger, M Plue, L Smith, FE Udris, EM McDonell, MB Eckert, GJ Temkit, M Zhou, XH Chen, LW Tierney, WM AF Subramanian, U Filn, SD Weinberger, M Plue, L Smith, FE Udris, EM McDonell, MB Eckert, GJ Temkit, M Zhou, XH Chen, LW Tierney, WM TI A controlled trial of including symptom data in computer-based care suggestions for managing patients with chronic heart failure SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; CLINICAL-PRACTICE GUIDELINES; CONTINUING MEDICAL-EDUCATION; ACUTE MYOCARDIAL-INFARCTION; PREVENTIVE CARE; HOSPITALIZED-PATIENTS; ELDERLY PATIENTS; HEALTH-STATUS; PHYSICIAN PERFORMANCE; CRITICAL-APPRAISAL AB BACKGROUND; Heart failure is common and associated with considerable morbidity and cost, yet physician adherence to treatment guidelines is suboptimal. We conducted a randomized controlled study to determine if adding symptom information to evidence-based, computer-generated care suggestions would affect treatment decisions among primary care physicians caring for outpatients with heart failure at two Veterans Affairs medical centers. METHODS: Physicians were randomly assigned to receive either care suggestions generated with electronic medical record data and symptom data obtained from questionnaires mailed to patients within 2 weeks of scheduled outpatient visits (intervention group) or suggestions generated with electronic medical record data alone (control group). Patients had to have a diagnosis of heart failure and objective evidence of left ventricular systolic dysfunction. We assessed physician adherence to heart failure guidelines, as well as patients' New York Heart Association (NYHA) class, quality of life, satisfaction with care, hospitalizations, and outpatient visits, at 6 and 12-months after enrollment. RESULTS: Patients in the intervention (n = 355) and control (n = 365) groups were similar at baseline. At 12 months, there were no significant differences in adherence to care suggestions between physicians in the intervention and control groups (33% vs. 30%, P = 0.4). There were also no significant changes in NYHA class (P = 0.1) and quality-of-life measures (P > 0.1), as well as no differences in the number of outpatient visits between intervention and control patients (6.7 vs. 7.1 visits, P = 0.48). Intervention patients were more satisfied with their physicians (P = 0.02) and primary care visit (P = 0.02), but had more all-cause hospitalizations at 6 months (1.5 vs. 0.7 hospitalizations, P = 0.0002) and 12 months (2.3 vs. 1.7 hospitalizations, P = 0.05). CONCLUSION: Adding symptom information to computer-generated care suggestions for patients with heart failure did not affect physician treatment decisions or improve patient outcomes. (C) 2004 by Excerpta. Medica Inc. C1 Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Div Gen Internal Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Div Biostat, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Regenstrief Inst Healthcare, Indianapolis, IN USA. NW Hlth Serv, Res & Dev Ctr Excellence, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Div Gen Internal Med, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Rochester, Div Cardiol, Rochester, NY USA. Univ Rochester, Dept Med, Rochester, NY USA. RP Tierney, WM (reprint author), Wishard Mem Hosp, Div Gen Internal Med & Geriatr, 1001 W 10th St,M200-OPW, Indianapolis, IN 46202 USA. EM wtierney@iupui.edu NR 80 TC 27 Z9 27 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR 15 PY 2004 VL 116 IS 6 BP 375 EP 384 DI 10.1016/j.amjmed.2003.11.021 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 802MC UT WOS:000220166600003 PM 15006586 ER PT J AU Fultz, SL McGinnis, KA Skanderson, M Ragni, MV Justice, AC AF Fultz, SL McGinnis, KA Skanderson, M Ragni, MV Justice, AC TI Association of venous thromboembolism with human immunodeficiency virus and mortality in veterans SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PROTEIN-S DEFICIENCY; AGING COHORT 3-SITE; HIV-INFECTION; THROMBOSIS; RISK; AIDS; DIAGNOSIS; DISEASE; CANCER C1 Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Hematol & Oncol, Pittsburgh, PA USA. Hemophilia Ctr Western Penn, Pittsburgh, PA USA. RP Justice, AC (reprint author), Vet Affairs Connecticut Healthcare Syst, Bldgd 2,Room 7-133,11-ACSLG,950 Campbell Ave, West Haven, CT 06516 USA. EM Amy.Justice2@med.va.gov FU NIA NIH HHS [AG00826]; NIAAA NIH HHS [AA13566] NR 20 TC 42 Z9 42 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR 15 PY 2004 VL 116 IS 6 BP 420 EP 423 DI 10.1016/j.amjmed.2003.10.011 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 802MC UT WOS:000220166600009 PM 15006592 ER PT J AU Flemons, WW Douglas, NJ Kuna, ST Rodenstein, DO Wheatley, J AF Flemons, WW Douglas, NJ Kuna, ST Rodenstein, DO Wheatley, J TI Access to diagnosis and treatment of patients with suspected sleep apnea SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID POSITIVE AIRWAY PRESSURE; TRIAL; CPAP C1 Univ Calgary, Fac Med, Calgary, AB T2N 2T9, Canada. Foothills Med Ctr, Calgary, AB T2N 2T9, Canada. Royal Infirm, Edinburgh, Midlothian, Scotland. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Catholique Louvain, Dept Pneumol, Clin Univ St Luc, B-1200 Brussels, Belgium. Westmead Hosp, Dept Resp Med, Wentworthville, NSW, Australia. RP Flemons, WW (reprint author), Univ Calgary, Fac Med, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM flemons@ucalgary.ca RI Douglas, Neil/B-1491-2013 NR 17 TC 249 Z9 255 U1 2 U2 4 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 MAR 15 PY 2004 VL 169 IS 6 BP 668 EP 672 DI 10.1164/rccm.200308-1124PP PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 802YP UT WOS:000220199100006 PM 15003950 ER PT J AU Mund, C Musch, T Strodicke, M Assmann, B Li, E Lyko, F AF Mund, C Musch, T Strodicke, M Assmann, B Li, E Lyko, F TI Comparative analysis of DNA methylation patterns in transgenic Drosophila overexpressing mouse DNA methyltransferases SO BIOCHEMICAL JOURNAL LA English DT Article DE DNA methyltransferase; Dnmt1; Dnmt2; Dnmt3a; Dnmt3b; Drosophila ID EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; NON-CPG METHYLATION; CYTOSINE-5 METHYLTRANSFERASES; IMMUNODEFICIENCY SYNDROME; MAMMALIAN DEVELOPMENT; ENZYMATIC-PROPERTIES; HISTONE DEACETYLASE; GENE-EXPRESSION; IN-VIVO AB DNA methyltransferases (Dnmts) mediate the epigenetic modification of eukaryotic genomes. Mammalian DNA methylation patterns are established and maintained by co-operative interactions among the Dnmt proteins Dnmt1, Dnmt3a and Dnmt3b. Owing to their simultaneous presence in mammalian cells, the activities of individual Dnmt have not yet been determined. This includes a fourth putative Dnmt, namely Dnmt2, which has failed to reveal any activity in previous assays. We have now established transgenic Drosophila strains that allow for individual overexpression of all known mouse Dnmts. Quantitative analysis of genomic cytosine methylation levels demonstrated a robust Dural activity for the de novo methyltransferases Dnmt3a and Dnmt3b. In addition, we also detected a weak but significant activity for Dnmt2. Subsequent methylation tract analysis by genomic bisulphite sequencing revealed that Dnmt3 enzymes preferentially methylated CpG dinucleotides in a processive manner, whereas Dnmt2 methylated isolated cytosine residues in a non-CpG dinucleotide context. Our results allow a direct comparison of the activities of mammalian Dnmts and suggest a significant functional specialization of these enzymes. C1 Deutsch Krebsforschungszentrum, Res Grp Epigenet, D-69120 Heidelberg, Germany. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Lyko, F (reprint author), Deutsch Krebsforschungszentrum, Res Grp Epigenet, Neuenheimer Feld 580, D-69120 Heidelberg, Germany. EM f.lyko@dkfz.de NR 38 TC 28 Z9 30 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 2004 VL 378 BP 763 EP 768 DI 10.1042/BJ20031567 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807DB UT WOS:000220481100007 PM 14636159 ER PT J AU Lyoo, IK Kim, MJ Stoll, AL Demopulos, CM Parow, AM Dager, SR Friedman, SD Dunner, DL Renshaw, PF AF Lyoo, IK Kim, MJ Stoll, AL Demopulos, CM Parow, AM Dager, SR Friedman, SD Dunner, DL Renshaw, PF TI Frontal lobe gray matter density decreases in bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; voxel-based morphometry; frontal lobe; gray matter; brain; magnetic resonance imaging ID SUBGENUAL PREFRONTAL CORTEX; MOOD DISORDERS; MRI; ABNORMALITIES; UNIPOLAR; BRAIN AB Background: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). Methods. Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. Results: Bipolar subjects bad decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 4 7, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. Conclusions. The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the light inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. McLean Hosp, Psychopharmacol Res Lab, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Bipolar Disorders Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Washington, Ctr Anxiety & Depress, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Ctr Anxiety & Depress, Dept Radiol, Seattle, WA 98195 USA. RP Lyoo, IK (reprint author), McLean Hosp, Brain Imaging Ctr, 115 Mill St, Belmont, MA 02478 USA. OI Kim, Justin/0000-0002-5886-8545 FU PHS HHS [MGH58681] NR 23 TC 172 Z9 176 U1 2 U2 9 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 MAR 15 PY 2004 VL 55 IS 6 BP 648 EP 651 DI 10.1016/j.biopsych.2003.10.017 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801PZ UT WOS:000220109100013 PM 15013835 ER PT J AU May, FS Chen, QC Gilbertson, MW Shenton, ME Pitman, RK AF May, FS Chen, QC Gilbertson, MW Shenton, ME Pitman, RK TI Cavum septum pellucidum in monozygotic twins discordant for combat exposure: Relationship to posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE septum pellucidum; stress disorders; posttraumatic; magnetic resonance imaging; twins; monozygotic ID SCHIZOPHRENIA; MRI AB Background Abnormally large cavum septum pellucidum has been reported in posttraumatic stress disorder; however, the origin of this association is uncertain. Methods: We utilized magnetic resonance imaging to measure cavum septum pellucidum in pairs of identical twins discordant for combat exposure in Vietnam. Results: Presence of abnormal cavum septum pellucidum was significantly correlated between exposed and unexposed twins, indicating that it is partially determined by heredity and/or shared environment. There was a greater proportion of cavum septum pellucidum in combat-exposed twins with posttraumatic stress disorder and their noncombat-exposed co-twins. Conclusions. The presence of abnormally large cavum septum pellucidum is a familial vulnerability factor for posttraumatic stress disorder. C1 Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. MIT, Undergrad Res Opportunities Program, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Psychiat Serv, Brockton, MA USA. VA Med Ctr, Res Serv, Manchester, NH USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, CNY 2616,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [R01-MH54636, K05 MH070047, R01 MH054636, K05 MH070047-03, K02-MH01110, R01 MH054636-06] NR 17 TC 30 Z9 30 U1 0 U2 0 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 MAR 15 PY 2004 VL 55 IS 6 BP 656 EP 658 DI 10.1016/j.biopsych.2003.09.018 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801PZ UT WOS:000220109100015 PM 15013837 ER PT J AU Ishiguro, K Xavier, R AF Ishiguro, K Xavier, R TI Homer-3 regulates activation of serum response element in T cells via its EVH1 domain SO BLOOD LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; WISKOTT-ALDRICH-SYNDROME; PROLINE-RICH MOTIF; IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; SYNDROME PROTEIN; IP3 RECEPTORS; MESSENGER-RNA; FAMILY; TRANSCRIPTION AB Drosophila enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) homology 1 (EVH1) domain proteins regulate signal transduction at the neuronal and immunologic synapse. Despite shared cell biologic machinery at these synapses, the regulation of client proteins that transmit synaptic activity to the nucleus is likely to be different. Homer-3, a member of the EVH1 family, is expressed in the thymus, suggesting a role for this protein in T-cell signal transduction. Upon T-cell receptor (TCR) engagement, Homer-3 was recruited to the contact area of Jurkat cells to anti-CD3 and CD28 antibody-coated beads prior to actin accumulation and was subsequently translocated into the nucleus. Overexpression of Homer-3 reduced transcriptional activation via the serum response element (SRE) in response to anti-CD3 antibody, phorbol ester, or dominant active Ha-Ras. Consistent with these results, knockdown of Homer-3 increased SRE activation. Homer-3 coprecipitated with CCAAT/enhancer binding protein beta (C/EBPbeta), one of the transcription factors that binds to the SRE and has a consensus motif binding to EVH1 domain. Moreover, Homer-3 and its EVH1 domain fragment reduced transcriptional activation of C/EBPbeta. These findings suggest that Homer-3 may be involved in the regulation of SRE activation in T cells via interaction between its EVH1 domain and C/EBPbeta. (C) 2004 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Xavier, R (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu NR 64 TC 26 Z9 26 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 MAR 15 PY 2004 VL 103 IS 6 BP 2248 EP 2256 DI 10.1182/blood-2003-08-2671 PG 9 WC Hematology SC Hematology GA 801VM UT WOS:000220123400044 PM 14645007 ER PT J AU Yao, DC Tolan, DR Murray, MF Harris, DJ Darras, BT Geva, A Neufeld, EJ AF Yao, DC Tolan, DR Murray, MF Harris, DJ Darras, BT Geva, A Neufeld, EJ TI Hemolytic anemia and severe rhabdomyolysis caused by compound heterozygous mutations of the gene for erythrocyte/muscle isozyme of aldolase, ALDOA((Arg303X/Cys338Tyr)) SO BLOOD LA English DT Article ID SUBSTRATE; SITE AB Aldolase (E.C. 4.1.2.13), a homotetrameric protein encoded by the ALDOA gene, converts fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. Three isozymes are encoded by distinct genes. The sole aldolase present in red blood cells and skeletal muscle is the A isozyme. We report here the case of a girl of Sicilian descent with aldolase A deficiency. Clinical manifestations included transfusion-dependent anemia until splenectomy at age 3 and increasing muscle weakness, with death at age 4 associated with rhabdomyolysis and hyperkalemia. Sequence analysis of the ALDOA coding regions revealed 2 novel heterozygous ALDOA mutations in conserved regions of the protein. The paternal allele encoded a nonsense mutation, Arg303X, in the enzyme-active site. The maternal allele encoded a missense mutation, Cys338Tyr, predicted to cause enzyme instability. This is the most severely affected patient reported to date and only the second with both rhabdomyolysis and hemolysis. (C) 2004 by The American Society of Hematology. C1 Childrens Hosp, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, 300 Longwood Ave,NRB8210, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; OI Tolan, Dean/0000-0002-0598-7241 FU NHLBI NIH HHS [HL04184]; NIDDK NIH HHS [DK43521] NR 15 TC 24 Z9 25 U1 0 U2 5 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 MAR 15 PY 2004 VL 103 IS 6 BP 2401 EP 2403 DI 10.1182/blood-2003-09-3160 PG 3 WC Hematology SC Hematology GA 801VM UT WOS:000220123400065 PM 14615364 ER PT J AU Clark, FJ Gregg, R Piper, K Dunnion, D Freeman, L Griffiths, M Begum, G Mahendra, P Craddock, C Moss, P Chakraverty, R AF Clark, FJ Gregg, R Piper, K Dunnion, D Freeman, L Griffiths, M Begum, G Mahendra, P Craddock, C Moss, P Chakraverty, R TI Chronic graft-versus-host disease is associated with increased numbers of peripheral blood CD4(+)CD25(high) regulatory T cells SO BLOOD LA English DT Article ID FUNCTIONAL-CHARACTERIZATION; L-SELECTIN; IN-VITRO; CD4(+); ANTIGEN; TRANSPLANTATION; VIVO; EXPRESSION; ORIGIN; IDENTIFICATION AB Chronic graft-versus-host disease (cGVHD) is characterized by a state of profound immunodeficiency in association with alloreactive and autoimmune phenomena. These observations indicate an impairment of immunologic tolerance that could involve both central and. peripheral mechanisms. Defective thymic function may contribute to dysregulation of central tolerance, but few studies have addressed peripheral tolerance. Recently a population of CD4(+)CD25(+) T cells (T-reg cells) has been characterized, which controls immunologic reactivity in vivo and which on transfer can prevent experimental acute GVHD. We investigated the number and function of peripheral blood CD4(+)CD25(high) T cells in patients more than 100 days after allogeneic hematopoietic stem cell transplantation. Patients with cGVHD had markedly elevated numbers of CD4(+)CD25(high) T cells as compared to patients without GVHD. CD4(+)CD25(high) T cells derived from patients in both groups were of donor origin, lacked markers of recent activation, and expressed intracellular CD152. In contrast to controls, CD4(+)CD25(high) T cells derived from patients with cGVHD were characterized by lower surface CD62L expression. In vitro, CD4+CD25high T cells were hyporesponsive to polyclonal stimulation and suppressed the proliferation and cytokine synthesis of CD4(+)CD25(-) cells, an effect that was independent of interleukin 10. These results indicate that chronic graft-versus-host injury does not occur as a result of Treg cell deficiency. (C) 2004 by The American Society of Hematology. C1 Univ Birmingham, Dept Hematol, Inst Canc Studies, Birmingham B15 2TT, W Midlands, England. Birmingham Womens Hosp, Reg Genet Lab, Birmingham, W Midlands, England. Univ Birmingham, Canc Res United Kingdom Clin Trials Unit, Birmingham, W Midlands, England. RP Chakraverty, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Biol Res Ctr,BMT Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM ronion.chakraverty@tbrc.mgh.harvard.edu NR 43 TC 154 Z9 167 U1 0 U2 3 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 MAR 15 PY 2004 VL 103 IS 6 BP 2410 EP 2416 DI 10.1182/blood-2003-06-2073 PG 7 WC Hematology SC Hematology GA 801VM UT WOS:000220123400068 PM 14604970 ER PT J AU Tzika, AA Astrakas, LG Zarifi, MK Zurakowski, D Poussaint, TY Goumnerova, L Tarbell, NJ Black, PM AF Tzika, AA Astrakas, LG Zarifi, MK Zurakowski, D Poussaint, TY Goumnerova, L Tarbell, NJ Black, PM TI Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumors SO CANCER LA English DT Article DE magnetic resonance; spectroscopy; brain; neoplasms in infants and children ID CEREBRAL BLOOD-VOLUME; IN-VIVO; GLIOBLASTOMA-MULTIFORME; PROTON SPECTROSCOPY; MR SPECTROSCOPY; RAT GLIOMA; CHOLINE; VITRO; METABOLISM; PHOSPHOCHOLINE AB BACKGROUND. in vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors. METHODS. MR spectroscopic imaging examinations were performed on 27 children with neuroglial brain tumors during therapy on a 1.5-Tesla MR system. Normalized rTBV values were measured in 11 of 27 patients. Each examination was rated as stable or progressive by clinical and imaging criteria. RESULTS. The percent change in normalized choline (Cho) was significantly greater in patients who had progressive examinations compared with patients who had stable examinations (P = 0.03). The percent change in Cho/N-acetylaspartate (Cho/NAA) was significantly higher in patients who had progressive outcomes (n = 18 patients) compared with patients who had stable outcomes (n = 32 patients; P < 0.001; sensitivity, 0.89; specificity, 0.88) and was identified as the most important prognostic indicator of tumor progression by logistic regression (likelihood ratio test, 33.4; P < 0.001). The odds of tumor progression were approximately 55 times greater for patients who showed at least a 20% change in Cho/NAA. rTBV distinguished between progressing and stable tumors (P = 0.03), and Cho/NAA and rTBV values showed interaction to predict the probability of a progressing clinical outcome. CONCLUSIONS. The percent change in Cho/NAA by proton MR spectroscopic imaging, assisted by rTBV, was useful in predicting tumor progression in children with brain tumors. (C) 2004 American Cancer Society. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Agia Sophia Childrens Hosp, Dept Diagnost Imaging, Athens, Greece. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,NMR Surg Lab, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 NR 36 TC 64 Z9 68 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2004 VL 100 IS 6 BP 1246 EP 1256 DI 10.1002/cncr.20096 PG 11 WC Oncology SC Oncology GA 802XC UT WOS:000220195200019 PM 15022293 ER PT J AU Oliveira, AM Hsi, BL Weremowicz, S Rosenberg, AE Dal Cin, P Joseph, N Bridge, JA Perez-Atayde, AR Fletcher, JA AF Oliveira, AM Hsi, BL Weremowicz, S Rosenberg, AE Dal Cin, P Joseph, N Bridge, JA Perez-Atayde, AR Fletcher, JA TI USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst SO CANCER RESEARCH LA English DT Article ID MOLECULAR-CLONING; PROSTATE-CANCER; CADHERIN; TRANSLOCATIONS; PROTEIN; CELLS AB Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation t(16;17)(q22;p13) creates a fusion gene in which the osteoblast cadherin 11 gene (CDH11) promoter region on 16q22 is juxtaposed to the entire ubiquitin-specific protease USP6 (Tre2) coding sequence on 17p13. CDHII-USP6 fusion transcripts were demonstrated only in ABC with t(16;17) but other ABCs had CDH11 or USP6 rearrangements resulting from alternate cytogenetic mechanisms. CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MI USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Pathol, Omaha, NE USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM amoliveira@partners.org NR 19 TC 104 Z9 107 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 MAR 15 PY 2004 VL 64 IS 6 BP 1920 EP 1923 DI 10.1158/0008-5472.CAN-03-2827 PG 4 WC Oncology SC Oncology GA 803RV UT WOS:000220249100006 PM 15026324 ER PT J AU Mehrotra, J Ganpat, MM Kanaan, Y Fackler, MJ McVeigh, M Lahti-Domenici, J Polyak, K Argani, P Naab, T Garrett, E Parmigiani, G Broome, C Sukumar, S AF Mehrotra, J Ganpat, MM Kanaan, Y Fackler, MJ McVeigh, M Lahti-Domenici, J Polyak, K Argani, P Naab, T Garrett, E Parmigiani, G Broome, C Sukumar, S TI Estrogen receptor/progesterone receptor-negative breast cancers of young African-American women have a higher frequency of methylation of multiple genes than those of Caucasian women SO CLINICAL CANCER RESEARCH LA English DT Article ID BRCA1 PROMOTER REGION; TUMOR-SUPPRESSOR GENE; DNA METHYLATION; SPORADIC BREAST; HYPERMETHYLATION; ASSOCIATION; EXPRESSION; DISEASE; RASSF1A; PCR AB Purpose: To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races. Experimental Design: HIN-1, Twist, Cyclin D2, RAR-R, and RASSF1A were analyzed in DNA from 67 AA and 44 Can invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR. Results: Significant differences between races were observed in the ER-/PR-, age < 50 subgroup; AA tumors had higher frequency of methylation (P < 0.001) in four of five genes as compared with Can and also a higher prevalence (80 versus 0%; P < 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER+/PR+ tumors in all ages and ER-/PR- tumors in age > 50. ER+/PR+ status was associated with higher frequency of methylation in Can tumors of all ages but only with the age > 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P = 0.01) with shorter survival time. Conclusion: ER-/PR-, age < 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Can women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races. C1 Howard Univ, Coll Med, Dept Biochem & Mol Biol, Ctr Canc, Washington, DC 20059 USA. Howard Univ, Ctr Canc, Dept Pathol, Washington, DC 20059 USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Breast Canc Program, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Clin Trials & Biometry, Baltimore, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Broome, C (reprint author), Howard Univ, Coll Med, Dept Biochem & Mol Biol, Ctr Canc, 520 W St NW, Washington, DC 20059 USA. EM cbroome@howard.edu FU NCI NIH HHS [U54CA91409, P50CA88843, U54CA91431] NR 33 TC 48 Z9 49 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 MAR 15 PY 2004 VL 10 IS 6 BP 2052 EP 2057 DI 10.1158/1078-0432.CCR-03-0514 PG 6 WC Oncology SC Oncology GA 804ZW UT WOS:000220337600026 PM 15041725 ER PT J AU Kho, AT Zhao, Q Cai, ZH Butte, AJ Kim, JYH Pomeroy, SL Rowitch, DH Kohane, IS AF Kho, AT Zhao, Q Cai, ZH Butte, AJ Kim, JYH Pomeroy, SL Rowitch, DH Kohane, IS TI Conserved mechanisms across development and tumorigenesis revealed by a mouse development perspective of human cancers SO GENES & DEVELOPMENT LA English DT Article DE cerebellar development; medulloblastoma; comparative genomics; multiscale models; metastasis; principle component analysis ID GENE-EXPRESSION; COMPARATIVE GENOMICS; STEM-CELL; METASTATIC MEDULLOBLASTOMA; DIFFERENTIATION; SYSTEM; IDENTIFICATION; INSIGHTS; TARGETS; LUNG AB identification of common mechanisms underlying organ development and primary tumor formation should yield new insights into tumor biology and facilitate the generation of relevant cancer models. We have developed a novel method to project the gene expression profiles of medulloblastomas (MBs)-human cerebellar tumors-onto a mouse cerebellar development sequence: postnatal days 1-60 (P1-P60). Genomically, human medulloblastomas were closest to mouse P1-P10 cerebella, and normal human cerebella were closest to mouse P30-P60 cerebella. Furthermore, metastatic MBs were highly associated with mouse P5 cerebella, suggesting that a clinically distinct subset of tumors is identifiable by molecular similarity to a precise developmental stage. Genewise, down- and up-regulated MB genes segregate to late and early stages of development, respectively. Comparable results for human lung cancer vis-a-vis the developing mouse lung suggest the generalizability of this multiscalar developmental perspective on tumor biology. Our findings indicate both a recapitulation of tissue-specific developmental programs in diverse solid tumors and the utility of tumor characterization on the developmental time axis for identifying novel aspects of clinical and biological behavior. C1 Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Rowitch, DH (reprint author), Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu; isaac_kohane@harvard.edu RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NHLBI NIH HHS [HL066582-01, U01 HL066582]; NIDDK NIH HHS [K12 DK063696, R01 DK00837]; NINDS NIH HHS [R01 NS4051, NS40828-01A1, P01 NS040828, P50 NS040828, R01 NS35701, R21 NS41764-01] NR 40 TC 111 Z9 112 U1 2 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2004 VL 18 IS 6 BP 629 EP 640 DI 10.1101/gad.1182504 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 811TM UT WOS:000220794200005 PM 15075291 ER PT J AU Cross, CK Berman, S Buswell, L Johnson, B Baldini, EH AF Cross, CK Berman, S Buswell, L Johnson, B Baldini, EH TI Prospective study of palliative hypofractionated radiotherapy (8.5 Gy x 2) for patients with symptomatic non-small-cell lung cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE hypofractionation; palliation; lung cancer ID RADIATION-THERAPY; RANDOMIZED TRIAL; INOPERABLE CARCINOMA; ONCOLOGY-GROUP; 2 FRACTIONS; NSCLC; IRRADIATION; TOXICITY; CRITERIA; RTOG AB Purpose: Hypofractionated chest radiotherapy regimens have provided excellent palliation of pulmonary symptoms in patients with inoperable non-small-cell lung cancer (NSCLC) and poor performance status in studies from Asia and Europe. We conducted a prospective study of this approach in patients from the United States. Methods and Materials: Twenty-three patients with symptomatic NSCLC and an Eastern Cooperative Oncology Group performance status of greater than or equal to2 were enrolled between December 1994 and October 2001. Two "involved-field" fractions of 8.5 Gy were delivered 1 week apart. Patients were assessed for efficacy, toxicity, and tumor response at baseline, treatment completion, and 1 week, 1 month, and 4 months after completing radiotherapy. Results: The median follow-up after treatment began was 4.3 months (range, 0.3-38). The median forced expiratory volume in 1 s and Eastern Cooperative Oncology Group performance status as measured at baseline was 1.05 L and 3, respectively. The most common presenting pulmonary symptoms were dyspnea (100%), cough (96%), anorexia/nausea (65%), and chest pain (52%). Between treatment completion and up to 4 months after treatment, dyspnea, cough, anorexia/nausea, chest pain, hoarseness, hemoptysis, and dysphagia had improved in 30%, 60%, 67%, 75%, 25%, 100%, and 100% of patients, respectively. No cases of treatment-related esophagitis, pneumonitis, or radiation myelopathy occurred. Progressive local disease was seen in only 1 (6%) of 18 assessable patients 4 months after treatment. Conclusion: For patients with poor performance status and inoperable NSCLC causing pulmonary symptoms, hypofractionated, involved-field radiotherapy, 8.5 Gy in two fractions, offers acceptable palliation with minimal toxicity. A clear advantage of the very short hypofractionated regimen is that it enables patients with a short expected survival time to spend more of their remaining time away from the hospital. (C) 2004 Elsevier Inc. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Joint Ctr Radiat Therapy,Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Cross, CK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Joint Ctr Radiat Therapy,Dept Radiat Oncol, 75 Francis St,ASB-1,L2 Level, Boston, MA 02115 USA. EM Ccross@partners.org NR 27 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2004 VL 58 IS 4 BP 1098 EP 1105 DI 10.1016/j.ijrobp.2003.08.005 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 801GK UT WOS:000220084200011 PM 15001250 ER PT J AU Viswanathan, AN Grier, HE Litman, HJ Perez-Atayde, A Tarbell, NJ Neuberg, D Shamberger, RC Marcus, KJ AF Viswanathan, AN Grier, HE Litman, HJ Perez-Atayde, A Tarbell, NJ Neuberg, D Shamberger, RC Marcus, KJ TI Outcome for children with Group III rhabdomyosarcoma treated with or without radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol DE pediatric; rhabdomyosarcoma; radiotherapy; surgery; chemotherapy ID OF-PEDIATRIC-ONCOLOGY; INTERGROUP RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; CHEMOTHERAPY AB Purpose: To analyze the sites of relapse, relapse-free survival, and overall survival in children with Group III rhabdomyosarcoma treated with or without radiotherapy (RT). Methods and Materials: The outcomes of 48 children with Group III rhabdomyosarcoma treated between 1980 and 1997 were evaluated. The median overall survival follow-up was 7.3 years. Of the 48 patients, 65% had embryonal histology. Local treatment after induction chemotherapy included complete surgical resection (CSR) alone in 9 (19%), CSR plus RT in 13 (27%), partial resection or rebiopsy plus RT in 10 (21%), and RT alone in 15 patients (31%). One child developed distant disease before completing local therapy. Results: Of the 48 patients, 12 developed relapse at local (n = 3), regional (n = 4), or distant (n = 5) sites. All 9 patients treated with CSR after induction chemotherapy had embryonal/botryoid histology. Only 1 of these 9 patients developed relapse. No statistically significant difference was found in overall survival (p = 0.95) or relapse-free survival (p = 0.67) between patients treated with or without RT. The Kaplan-Meier estimate of 5-year overall survival and relapse-free survival was 76% +/- 7% and 74% +/- 7%, respectively. Significant predictors of relapse-free survival on univariate analysis included CSR (p = 0.03), nodal positivity (p = 0.001), and embryonal histology (p = 0.0003). On multivariate analysis, embryonal histology was the most significant predictor of relapse-free (p = 0.001) and overall (p = 0.01) survival. Conclusion: The overall survival for children with Group III rhabdomyosarcoma in this series was favorable. Embryonal/botryoid histology was the most significant predictor of both overall and relapse-free survival. We found that for a selected subgroup of children with embryonal histology, induction chemotherapy followed by complete surgical resection alone may be adequate local therapy. (C) 2004 Elsevier Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L2, Boston, MA 02115 USA. EM aviswanathan@partners.org OI Viswanathan, Akila/0000-0002-2003-0392 NR 20 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2004 VL 58 IS 4 BP 1208 EP 1214 DI 10.1016/j.ijrobp.2003.08.027 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 801GK UT WOS:000220084200026 PM 15001265 ER PT J AU Roy, R Kohles, SS Zaporojan, V Peretti, GM Randolph, MA Xu, JW Bonassar, LJ AF Roy, R Kohles, SS Zaporojan, V Peretti, GM Randolph, MA Xu, JW Bonassar, LJ TI Analysis of bending behavior of native and engineered auricular and costal cartilage SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE auricular cartilage; tissue engineering; biomechanics; soft-tissue deformation; large-deflection bending ID ARTICULAR-CARTILAGE; STRESS-RELAXATION; COMPRESSION; ELECTROMECHANICS AB A large-deflection elasticity model was used to describe the mechanical behavior of cartilaginous tissues during three-point bending tests. Force-deflection curves were measured for 20-mm long x 4-mm wide x approximate to1-mm thick strips of porcine auricular and costal cartilage. Using a least-squares method with elastic modulus in bending as the only adjustable parameter, data were fit to a model based on the von Karman theory for large deflection of plates. This model described the data well, with an average RMS error of 14.8% and an average R-2 value of 0.98. Using this method, the bending modulus of auricular cartilage (4.6 MPa) was found to be statistically lower (p < 0.05) than that of costal cartilage (7.1 MPa). Material features of the cartilage samples influenced the mechanical behavior, including the orientation of the perichondrium in auricular cartilage. These methods also were used to determine the elastic moduli of engineered cartilage samples produced by seeding chondrocytes into fibrin glue. The modulus of tissue-engineered constructs increased statistically with time (p < 0.05), but still were statistically lower than the moduli of the native tissue samples (p > 0.05), reaching only about a third of the values of native samples. (C) 2004 Wiley Periodicals, Inc. C1 Univ Massachusetts, Sch Med, Ctr Tissue Engn, Worcester, MA 01602 USA. Worcester Polytech Inst, Worcester, MA 01609 USA. Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. RP Bonassar, LJ (reprint author), Univ Massachusetts, Sch Med, Ctr Tissue Engn, 1 Biotech,Suite 190,55 Lake Ave N, Worcester, MA 01602 USA. EM lb244@cornell.edu RI Bonassar, Lawrence/C-2103-2016; OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187; Kohles, Sean/0000-0002-5869-7715 NR 25 TC 36 Z9 36 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 15 PY 2004 VL 68A IS 4 BP 597 EP 602 DI 10.1002/jbm.a.10068 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 779CG UT WOS:000189277600001 PM 14986315 ER PT J AU Colombo, G Langer, R Kohane, DS AF Colombo, G Langer, R Kohane, DS TI Effect of excipient composition on the biocompatibility of bupivacaine-containing microparticles at the sciatic nerve SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE prolonged duration local anesthesia; controlled release; epineurium; inflammation; myotoxicity ID DURATION LOCAL-ANESTHESIA; PROTEIN-SUGAR PARTICLES; DRUG-DELIVERY; IN-VIVO; MICROSPHERES; BLOCKADE; TETRODOTOXIN; MYOTOXICITY; SHEEP; RAT AB Microparticulate formulations are often used for experimental prolongation of nerve blockade. Here we examine the effect of excipient composition on the biocompatibitity of bupivacaine-containing microparticles. Lipid-protein-sugar oparticles (LPSPs) composed of 3% (1.3-mum diameter) and 60% (4.7-mum diameter) (w/w) dipalmitoylphosphatidylcholine (DPPC) were produced by spray drying, containing 10% (w/w) bupivacaine. Rat sciatic nerve blocks with 75 mg of particles produced statistically similar durations of sensory nerve block [3% (w/w) DPPC particles: 301 min; 60% (w/w) DPPC particles: 321 min]. Examination of tissues 1 day after injection revealed large particle deposits and acute inflammation in animals that received 60% (w/w) DPPC particles. There were no visible deposits in those that received 3% (w/w) DPPC particles, and microscopic inflammation was reduced. The difference between groups was similar 4 days after injection. Two weeks after injection, there was no particulate mass in either group, and inflammation had largely resolved. In both groups, moderately severe myotoxicity was seen 1 and 4 days after injection but had largely resolved by 2 weeks. In summary, reduction in particles' DPPC content greatly improved biocompatibility without compromising duration of nerve blockade; the improvement was probably attributable to the enhanced rate of particle resorption. (C) 2004 Wiley Periodicals, Inc. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Parma, Dept Pharmaceut, I-43100 Parma, Italy. Massachusetts Gen Hosp, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Kohane, DS (reprint author), MIT, Dept Chem Engn, Bldg 25-342,77 Main St, Cambridge, MA 02139 USA. EM dkohane@partners.org RI Colombo, Gaia/G-6837-2012 OI Colombo, Gaia/0000-0001-9033-2305 FU NIGMS NIH HHS [GM00684, GM26698] NR 22 TC 17 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 15 PY 2004 VL 68A IS 4 BP 651 EP 659 DI 10.1002/jbm.a.20074 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 779CG UT WOS:000189277600006 PM 14986320 ER PT J AU Garber, JE Hartman, AR AF Garber, JE Hartman, AR TI Prophylactic oophorectomy and hormone replacement therapy: Protection at what price? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; BREAST-CANCER; POSTMENOPAUSAL WOMEN; BRCA2 MUTATIONS; HIGH-RISK; CARRIERS; MAMMOGRAPHY; GENE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 16 TC 15 Z9 15 U1 1 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 MAR 15 PY 2004 VL 22 IS 6 BP 978 EP 980 DI 10.1200/JCO.2004.01.926 PG 3 WC Oncology SC Oncology GA 804GT UT WOS:000220287900003 PM 14981100 ER PT J AU Fernandez-Teijeiro, A Betensky, RA Sturla, LM Kim, JYH Tamayo, P Pomeroy, SL AF Fernandez-Teijeiro, A Betensky, RA Sturla, LM Kim, JYH Tamayo, P Pomeroy, SL TI Combining gene expression profiles and clinical parameters for risk stratification in medulloblastomas SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHILDRENS CANCER GROUP; NEUROECTODERMAL BRAIN-TUMORS; PROGNOSTIC-FACTORS; RECEPTOR TRKC; DIFFERENTIATION; INSTITUTION; PREDICTION; RECURRENCE; SURVIVAL; ONCOLOGY AB Purpose Stratification of risk in patients with medulloblastoma remains a challenge. As clinical parameters have been proven insufficient for accurately defining disease risk, molecular markers have become the focus of interest. Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles. Patients and Methods In a cohort of 55 young patients (whose medulloblastoma samples have been analyzed previously for gene expression profile), associations between clinical and gene expression variables and survival were assessed using Cox proportional hazards models. Available clinical variables included age, stage (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype, treatment, and status. Results Univariate analysis demonstrated expression profiles to be the only significant clinical prognostic factor (P = .03). In multivariate analysis, gene expression profiles predicted outcome independent of other criteria. Clinical criteria did not significantly contribute additional information for outcome predictions, although an exploratory analysis noted a trend for decreased survival of patients with metastases at diagnosis but favorable gene expression profile. Conclusion Gene expression profiling predicts medulloblastoma outcome independent of clinical variables. These results need to be validated in a larger prospective study. (C) 2004 by American Society of Clinical Oncology. C1 Childrens Hosp, Dept Neurol, Div Neurosci, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Biomed Res, Cambridge, MA 02142 USA. Hosp Cruces Baracaldo, Unidad Oncol Pediat, Baracaldo, Basque Country, Spain. RP Pomeroy, SL (reprint author), Childrens Hosp, Dept Neurol, Div Neurosci, Dept Med, Enders 260,300 Longwood Ave, Boston, MA 02115 USA. EM scott.pomeroy@childrens.harvard.edu FU NICHD NIH HHS [HD 18655]; NINDS NIH HHS [NS35701] NR 31 TC 44 Z9 45 U1 1 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 MAR 15 PY 2004 VL 22 IS 6 BP 994 EP 998 DI 10.1200/JCO.2004.03.036 PG 5 WC Oncology SC Oncology GA 804GT UT WOS:000220287900006 PM 14970184 ER PT J AU Rebbeck, TR Friebel, T Lynch, HT Neuhausen, SL van't Veer, L Garber, JE Evans, GR Narod, SA Isaacs, C Matloff, E Daly, MB Olopade, OI Weber, BL AF Rebbeck, TR Friebel, T Lynch, HT Neuhausen, SL van't Veer, L Garber, JE Evans, GR Narod, SA Isaacs, C Matloff, E Daly, MB Olopade, OI Weber, BL TI Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID WOMEN; EFFICACY; RECONSTRUCTION; OOPHORECTOMY; EXPERIENCE; TAMOXIFEN AB Purpose Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations. Patients and Methods Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth, Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable. Results Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries. Conclusion Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%. (C) 2004 by American Society of Clinical Oncology. C1 Univ Penn, Abramson Family Canc Res Inst, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Creighton Univ, Omaha, NE 68178 USA. Univ Calif Irvine, Div Genet Epidemiol, Dept Med, Irvine, CA USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. Netherlands Canc Inst, Amsterdam, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. St Marys Hosp, Manchester M13 0JH, Lancs, England. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Yale Univ, New Haven, CT USA. Univ Chicago, Chicago, IL 60637 USA. RP Weber, BL (reprint author), Univ Penn, Abramson Family Canc Res Inst, Ctr Clin Epidemiol & Biostat, 514 BRB2,421 Curie blvd, Philadelphia, PA 19104 USA. EM weberb@mail.med.upenn.edu OI Evans, Gareth/0000-0002-8482-5784 FU NCI NIH HHS [CA57601, CA74415, N01-CN-6700, R01-CA83855] NR 19 TC 500 Z9 516 U1 3 U2 30 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 MAR 15 PY 2004 VL 22 IS 6 BP 1055 EP 1062 DI 10.1200/JCO.2004.04.188 PG 8 WC Oncology SC Oncology GA 804GT UT WOS:000220287900014 PM 14981104 ER PT J AU Greenberg, PL Lee, SJ Advani, R Tallman, MS Sikic, BI Letendre, L Dugan, K Lum, B Chin, DL Dewald, G Paietta, E Bennett, JM Rowe, JM AF Greenberg, PL Lee, SJ Advani, R Tallman, MS Sikic, BI Letendre, L Dugan, K Lum, B Chin, DL Dewald, G Paietta, E Bennett, JM Rowe, JM TI Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: A phase III trial (E2995) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; MEDIATED MULTIDRUG RESISTANCE; LIQUID-CHROMATOGRAPHIC METHOD; P-GLYCOPROTEIN EXPRESSION; SOUTHWEST-ONCOLOGY-GROUP; CLINICAL-SIGNIFICANCE; SDZ PSC-833; NONIMMUNOSUPPRESSIVE CYCLOSPORINE; POPULATION PHARMACOKINETICS; MODULATOR PSC-833 AB Purpose To determine whether adding the multidrug resistance gene-1 (MDR-1) modulator valspodar (PSC 833, Novartis Pharmaceuticals, Hanover, NJ) to chemotherapy provided clinical benefit to patients with poor-risk acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Patients and Methods A phase III randomized study was performed using valspodar plus mitoxantrone, etoposide, and cytarabine (PSC-MEC; n = 66) versus MEC (n = 63) to treat patients with relapsed or refractory AML and high-risk MDS. Results For the PSC-MEC versus MEC arms, complete response (CR) was achieved in 17% versus 25% of patients, respectively (P = not significant). For patients who had not received prior intensive chemotherapy (i.e, with secondary AML or high-risk MDS), the CR rate was increased-35% versus 15% for the remaining patients (P = .018), CR rates did not differ between treatment arms. The median disease-free survival in those achieving CR was similar in the two arms (10 versus 9.3 months) as was the patients' overall survival (4.6 versus 5.4 months). The CR rates in MDR+ (69% of patients) versus MDR- patients were similar for those receiving either chemotherapy regimen (16% versus 24%). The CR rate for unfavorable cytogenetic patients (45% of patients) was 13% compared to the remainder, 28% (P = .09). Population pharmacokinetic analysis demonstrated that the clearances of mitoxantrone and etoposide were decreased by 59% and 50%, respectively, supporting the empiric dose reductions in the PSC-MEC arm designed in anticipation of drug interactions between valspodar and the chemotherapeutic agents. Conclusion CR rates and overall survival were not improved by using PSC-MEC compared to MEC chemotherapy alone in patients with poor-risk AML or high-risk MDS. C1 Stanford Univ, Div Hematol, Med Ctr, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Univ Rochester, Wilmot Canc Ctr, Ctr Med, Rochester, NY USA. Rambam Med Ctr, Haifa, Israel. RP Greenberg, PL (reprint author), Stanford Univ, Div Hematol, Med Ctr, 703 Welch Rd,Suite G-1, Stanford, CA 94305 USA. EM peterg@stanford.edu RI Chin, David/M-3956-2015 OI Chin, David/0000-0002-2341-6207 FU NCI NIH HHS [CA11083, CA 52168, CA13650, CA17145, CA21115, CA23318, CA66636, R01 CA092474, U10 CA180816]; NCRR NIH HHS [M01 RR 00070] NR 53 TC 137 Z9 142 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 MAR 15 PY 2004 VL 22 IS 6 BP 1078 EP 1086 DI 10.1200/JCO.2004.07.048 PG 9 WC Oncology SC Oncology GA 804GT UT WOS:000220287900017 PM 15020609 ER PT J AU Byrd, JC Ruppert, AS Mrozek, K Carroll, AJ Edwards, CG Arthur, DC Pettenatti, MJ Stamberg, J Koduru, PRK Moore, JO Mayer, RJ Davey, FR Larson, RA Bloomfield, CD AF Byrd, JC Ruppert, AS Mrozek, K Carroll, AJ Edwards, CG Arthur, DC Pettenatti, MJ Stamberg, J Koduru, PRK Moore, JO Mayer, RJ Davey, FR Larson, RA Bloomfield, CD TI Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; AML COOPERATIVE GROUP; CYTOSINE-ARABINOSIDE; CYTOGENETIC ABNORMALITIES; CUMULATIVE INCIDENCE; PROGNOSTIC VALUE; THERAPY AB Purpose To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and nv(16)(p13q22) or t(16;16)(p13;q22). Patients and Methods We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one Course of HDAC followed by alternative intensive consolidation therapy. Results Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93, 5-year OS, 75% for the three to four cycles of HDAC group v70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. Conclusion We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC. C1 Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC USA. Wake Forest Univ, Ctr Med, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Natl Canc Inst, Bethesda, MD USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. N Shore Univ Hosp, Manhasset, NY USA. SUNY Upstate Med Univ, Syracuse, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol & Oncol, B302A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM byrd-3@medctr.osu.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA77658, CA101140, CA16058, CA31946] NR 33 TC 107 Z9 112 U1 1 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 MAR 15 PY 2004 VL 22 IS 6 BP 1087 EP 1094 DI 10.1200/JCO.2004.07.012 PG 8 WC Oncology SC Oncology GA 804GT UT WOS:000220287900018 PM 15020610 ER PT J AU Mapara, MY Sykes, M AF Mapara, MY Sykes, M TI Tolerance and cancer: Mechanisms of tumor evasion and strategies for breaking tolerance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID T-CELL TOLERANCE; GROWTH-FACTOR-BETA; ACTIVE SPECIFIC IMMUNOTHERAPY; RECOMBINANT VACCINIA VIRUS; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; IMMUNE-RESPONSES; METASTATIC MELANOMA; IN-VIVO; PHASE-I AB The development of malignant disease might be seen as a failure of immune surveillance. However, not all tumors are naturally immunogenic, and even among those that are immunogenic, the uncontrolled rapid growth of a tumor may sometimes out-run a robust immune response. Nevertheless, recent evidence suggests that mechanisms of tolerance that normally exist to prevent autoimmune disease may also preclude the development of an adequate antitumor response and that tumors themselves have the ability to thwart the development of effective immune responses against their antigens. A major challenge has been to develop approaches to breaking this tolerance in tumor-bearing hosts, and recent advances in our understanding of antigen presentation and tolerance have led to some promising strategies. An alternative approach is to use T cells from nontumor-bearing, allogeneic hosts in the form of lymphocyte infusions, with or without hematopoietic cell transplantation. Immunotherapy may occur in this setting via the response of nontolerant, tumor antigen-specific T cells from nontumor-bearing hosts or via the powerful destructive effect of an alloresponse directed against antigens shared by malignant cells in the recipient. Approaches to exploiting this beneficial effect without the deleterious consequence of graft-versus-host disease in allogeneic hematopoietic cell recipients are discussed. C1 Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. Humboldt Univ, Univ Med Ctr Charite, Dept Hematol & Oncol, Berlin, Germany. RP Sykes, M (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Sch Med, Massachusetts Gen Hosp, MGH-E Bldg 149-5102, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu RI mapara, markus/A-2134-2013 FU NCI NIH HHS [1 R01 CA 79986-03, 1 R01 CA 79989-03] NR 100 TC 185 Z9 192 U1 1 U2 14 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 MAR 15 PY 2004 VL 22 IS 6 BP 1136 EP 1151 DI 10.1200/JCO.2004.10.041 PG 16 WC Oncology SC Oncology GA 804GT UT WOS:000220287900024 PM 15020616 ER PT J AU Reichlin, A Gazumyan, A Nagaoka, H Kirsch, KH Kraus, M Rajewsky, K Nussenzweig, MC AF Reichlin, A Gazumyan, A Nagaoka, H Kirsch, KH Kraus, M Rajewsky, K Nussenzweig, MC TI A B cell receptor with two Ig alpha cytoplasmic domains supports development of mature but anergic B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE B cell receptor; immunoglobulin; signal transduction; anergy; B cell development ID TYROSINE ACTIVATION MOTIF; ADAPTER PROTEIN SLP-65; KINASE-C-DELTA; FACTOR-KAPPA-B; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; ALLELIC EXCLUSION; MICE LACKING; IMMUNOGLOBULIN (IG)ALPHA; POSITIVE SELECTION AB B cell receptor (BCR) signaling is mediated through immunoglobulin (Ig)alpha and Igbeta a membrane-bound heterodimer. Igalpha and Igbeta are redundant in their ability to support early B cell development, but their roles in mature B cells have not been defined. To examine the function of Igalpha-Igbeta in mature B cells in vivo we exchanged the cytoplasmic domain of Iga for the cytoplasmic domain of Igbeta by gene targeting (Igbeta(c)-->alpha(c) mice). Igbeta(c)-->alpha(c) B cells had lower levels of surface IgM and higher levels of BCR internalization than wild-type B cells. The mutant B cells were able to complete all stages of development and were long lived, but failed to differentiate into B1a cells. In addition, Igbeta(c-->)alpha(c) B cells showed decreased proliferative and Ca2+ responses to BCR stimulation in vitro, and were anergic to T-independent and -dependent antigens in vivo. C1 Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Kyoto Univ, Grad Sch Med, Dept Med Chem & Mol Biol, Sakyo Ku, Kyoto 6068501, Japan. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Nussenzweig, MC (reprint author), 1230 York Ave,Box 220, New York, NY 10021 USA. EM nussen@mail.rockefeller.edu OI Kirsch, Kathrin/0000-0003-1532-1715 FU PHS HHS [R03] NR 83 TC 17 Z9 19 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 MAR 15 PY 2004 VL 199 IS 6 BP 855 EP 865 DI 10.1084/jem.20031140 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 804YW UT WOS:000220335000012 PM 15024049 ER PT J AU Nolte, MA Arens, R Kraus, M van Oers, MHJ Kraal, G van Lier, RAW Mebius, RE AF Nolte, MA Arens, R Kraus, M van Oers, MHJ Kraal, G van Lier, RAW Mebius, RE TI B cells are crucial for both development and maintenance of the splenic marginal zone SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SECONDARY LYMPHOID-TISSUES; BRUTONS TYROSINE KINASE; TUMOR-NECROSIS-FACTOR; BETA-DEFICIENT MICE; TRANSGENIC MICE; LYMPHOTOXIN-ALPHA; ABNORMAL-DEVELOPMENT; VASCULAR ADDRESSIN; GENE-EXPRESSION; T-CELLS AB The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp. Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the spleen its specialized function in antibacterial immunity. In this study, we demonstrate that both development and maintenance of this marginal zone is highly dependent on the presence of B cells. Spleens from B cell-deficient mice were found to lack both metallophilic and marginal zone macrophages as well as mucosal addressin cellular adhesion molecule-1(+) sinus lining cells. Using an inducible Cre/loxP-driven mouse model in which mature B cells could be partially depleted by removal of the B cell receptor subunit Igalpha, we could show that the integrity and function of an established marginal zone was also dependent on the presence of B cells. This was confirmed in a transgenic model in which all B cells were gradually depleted due to overexpression of the TNF family member CD70. The loss of all cellular subsets from the marginal zone in these CD70 transgenic mice was effectively prevented by crossing these mice on a CD27(-/-) or TCRalpha(-/-) background, because this prohibited the ongoing B cell depletion. Therefore, we conclude that B cells are not only important for the development, but also for maintenance, of the marginal zone. This direct correlation between circulating B cells and the function of the spleen implies. an increased risk for B cell lymphopenic patients with bacterial infections. C1 Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, NL-1007 MB Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Hematol, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Expt Immunol Lab, NL-1105 AZ Amsterdam, Netherlands. Harvard Univ, Sch Med, Ctr Blood Res, Biomed Res Inst, Boston, MA 02115 USA. RP Mebius, RE (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Mol Cell Biol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM R.Mebius@vumc.nl OI van Lier, Rene/0000-0002-3201-7144 FU PHS HHS [R01 A1054636-01] NR 52 TC 55 Z9 56 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2004 VL 172 IS 6 BP 3620 EP 3627 PG 8 WC Immunology SC Immunology GA 801KY UT WOS:000220096000034 PM 15004164 ER PT J AU Sekine, H Watanabe, H Gilkeson, GS AF Sekine, H Watanabe, H Gilkeson, GS TI Enrichment of anti-glomerular antigen antibody-producing cells in the kidneys of MRL/MpJ-Fas(lpr) mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DNA ANTIBODIES; MURINE LUPUS; B-CELLS; SOMATIC HYPERMUTATION; LPR MICE; NEPHRITIS; AUTOANTIBODIES; SERUM; SELECTION AB Lupus nephritis is characterized by immune complex deposition and infiltration of inflammatory cells into the kidney including Ab-producing cells (AbPCs). Although AbPCs play a central role in the pathogenesis of immune complex glomerulonephritis in lupus, the specificity and pathogenic role of AbPCs infiltrating into the kidneys in Inputs are poorly understood. To characterize AbPCs present in lupus kidneys, we isolated AbPCs from diseased MRL/MpJ-Fas(lpr) (MRL/lpr) mouse kidneys. ELISPOT assays, using glomerular Ag (GA) extracts as Ag, demonstrated significant enhancement of anti-GA AbPCs in the kidneys as compared in peripheral blood or spleen of the same mouse. We isolated hybridomas with anti-GA specificity from MRL/lpr mouse kidneys. All the anti-GA mAbs had polyreactive binding to ssDNA, dsDNA, and IgG (i.e., rheumatoid factor), but not to histories or Sm. Sequence analysis of anti-GA Abs suggested the occurrence of somatic mutations and amino acid replacement in complementarity-determining regions with a high replacement to silent ratio resulting in charged amino acids. Intravenous administration of the monoclonal anti-GA Abs into BALB/c mice resulted in graded deposition in glomeruli paralleling their ELISA anti-GA reactivity. These results suggest that AbPCs infiltrating the kidneys in MRL/lpr mice accumulate as a result of Ag selection and likely play a pathologic role in lupus nephritis. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Div Rheumatol & Immunol, 96 Jonathon Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. EM gilkeson@musc.edu NR 47 TC 31 Z9 34 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 MAR 15 PY 2004 VL 172 IS 6 BP 3913 EP 3921 PG 9 WC Immunology SC Immunology GA 801KY UT WOS:000220096000069 PM 15004199 ER PT J AU Lorenzl, S Albers, DS Chirichigno, JW Augood, SJ Beal, MF AF Lorenzl, S Albers, DS Chirichigno, JW Augood, SJ Beal, MF TI Elevated levels of matrix metalloproteinases-9 and-1 and of tissue inhibitors of MMPs, TIMP-1 and TIMP-2 in postmortem brain tissue of progressive supranuclear palsy SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE matrix metalloproteinases; supranuclear palsy; substantia nigra ID NINDS NEUROPATHOLOGIC CRITERIA; AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE BRAIN; SPINAL-CORD; EXPRESSION; MATRIX-METALLOPROTEINASE-9; LOCALIZATION; ACTIVATION; DEMENTIA; CULTURES AB We determined the levels and tissue localization of matrix metalloproteinases (MMPs) as well as their endogenous tissue inhibitors (TIMPs) in postmortem brain tissue from 13 patients with progressive supranuclear palsy (PSP) and 8 age-matched controls. MMP-9 expression was significantly increased in both the frontal cortex (p = 0.002) and substantia nigra (p = 0.003) of PSP cases as compared to controls whereas MMP-1 levels were increased in the substantia nigra (p = 0.01) but unchanged in the frontal cortex (p = 0.41). Levels of the endogenous tissue inhibitors of MMPs, TIMP-1 and TIMP-2 were significantly elevated in the substantia nigra (TIMP-1: p = 0.004, TIMP-2: p = 0.01). Levels of TIMPs were unchanged in PSP frontal cortex as compared to control cases. Together, these data show alterations of MMPs and TIMPs in the substantia nigra as well as in the frontal cortex of PSP, consistent with the possibility that alterations in MMPs/TIMPs may contribute to disease pathogenesis. (C) 2003 Elsevier B.V. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, Room A-501, New York, NY 10021 USA. EM fbeal@med.cornell.edu NR 34 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2004 VL 218 IS 1-2 BP 39 EP 45 DI 10.1016/j.jns.2003.10.015 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 775WW UT WOS:000189084500007 PM 14759631 ER PT J AU Grauer, JN Vaccaro, AR Beiner, JM Kwon, BK Hilibrand, AS Harrop, JS Anderson, G Hurlbert, J Fehlings, MG Ludwig, SC Hedlund, R Arnold, PM Bono, CM Brodke, DS Dvorak, MFS Fischer, CG Sledge, JB Shaffrey, CI Schwartz, DG Sears, WR Dickman, C Sharan, A Albert, TJ Rechtine, GR AF Grauer, JN Vaccaro, AR Beiner, JM Kwon, BK Hilibrand, AS Harrop, JS Anderson, G Hurlbert, J Fehlings, MG Ludwig, SC Hedlund, R Arnold, PM Bono, CM Brodke, DS Dvorak, MFS Fischer, CG Sledge, JB Shaffrey, CI Schwartz, DG Sears, WR Dickman, C Sharan, A Albert, TJ Rechtine, GR TI Similarities and differences in the treatment of spine trauma between surgical specialties and location of practice SO SPINE LA English DT Article ID CERVICAL-SPINE; MANAGEMENT; FRACTURES; AXIS AB Study Design. Questionnaires administered to practicing orthopedic and neurosurgical spine surgeons from various regions of the United States and abroad. Objectives. To determine similarities and differences in the treatment of spinal trauma. Summary of Background Data. Spinal trauma is generally referred to subspecialists of orthopedic or neurosurgical training. Prior studies have suggested that there is significant variability in the management of such injuries. Methods. Questionnaires based on eight clinical scenarios of commonly encountered cervical, thoracic, and lumbar injuries were administered to 35 experienced spinal surgeons. Surgeons completed profile information and answered approximately one dozen questions for each case. Data were analyzed with SPSS software to determine the levels of agreement and characteristics of respondents that might account for a lack of agreement on particular aspects of management. Results. Of the 35 surgeons completing the questionnaire, 63% were orthopedists, 37% were neurosurgeons, and 80% had been in practice for more than 5 years. Considerable agreement was found in the majority of clinical decisions, including whether or not to operate and the timing of surgery. Of the differences noted, neurosurgeons were more likely to obtain a MRI, and orthopedists were more likely to use autograft as a sole graft material. Physicians from abroad were, in general, more likely to operate and to use an anterior approach during surgery than physicians from the northeastern United States. Conclusions. More commonalities were identified in the management of spinal trauma than previously reported. When found, variability in opinion was related to professional and regional differences. C1 Yale Univ, Sch Med, Dept Orthopaed & Rehabil, New Haven, CT 06520 USA. Thomas Jefferson Univ, Rothman Inst, Philadelphia, PA 19107 USA. Connecticut Orthopaed Specialists, New Haven, CT USA. Univ British Columbia, Dept Orthopaed, Combined Neurosurg & Orthopaed Spine Program, Vancouver, BC V5Z 1M9, Canada. Thomas Jefferson Univ, Dept Neurosurg, Philadelphia, PA 19107 USA. Univ Virginia, Dept Orthopaed, Charlottesville, VA USA. Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. Univ Calgary, Dept Clin Neurosci, Div Neurosurg, Calgary, AB, Canada. Univ Calgary, Dept Surg, Div Orthopaed Surg, Calgary, AB, Canada. Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Univ Maryland Orthopaed Associates, Baltimore, MD USA. Huddinge Univ Hosp, Orthopaed Clin, Stockholm, Sweden. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Boston Univ, Dept Orthopaed Surg, Boston, MA 02215 USA. Univ Utah, Med Ctr, Salt Lake City, UT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Indianapolis, IN USA. Methodist Hosp, Sydney, NSW, Australia. Barrow Neurol Associates, Phoenix, AZ USA. Albany Med Ctr, Div Orthopaed Surg, Albany, NY USA. Univ Florida, Div Orthopaed & Rehabil, Gainesville, FL USA. RP Grauer, JN (reprint author), Yale Univ, Sch Med, Dept Orthopaed & Rehabil, POB 208071, New Haven, CT 06520 USA. EM jonathan.grauer@yale.edu NR 12 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 15 PY 2004 VL 29 IS 6 BP 685 EP 696 DI 10.1097/01.BRS.0000115137.11276.0E PG 12 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 804EG UT WOS:000220281400013 PM 15014280 ER PT J AU Delgado-Borrego, A Casson, D Schoenfeld, D Somsouk, M Terella, A Jordan, SH Bhan, A Baid, S Cosimi, AB Pascual, M Chung, RT AF Delgado-Borrego, A Casson, D Schoenfeld, D Somsouk, M Terella, A Jordan, SH Bhan, A Baid, S Cosimi, AB Pascual, M Chung, RT TI Hepatitis C virus is independently associated with increased insulin resistance after liver transplantation SO TRANSPLANTATION LA English DT Article ID DIABETES-MELLITUS; NONALCOHOLIC STEATOHEPATITIS; MYCOPHENOLATE-MOFETIL; GLUCOSE-TOLERANCE; RISK-FACTORS; INFECTION; CIRRHOSIS; PREVALENCE; ALCOHOL; RECIPIENTS AB Background and Aims. There is a strong epidemiologic association between diabetes mellitus (DM) and hepatitis C virus (HCV) infection. However, the pathogenetic basis for this association has not been established. We sought to evaluate the association between insulin resistance (111), beta-cell dysfunction, and HCV among orthotopic liver transplant (OLT) recipients. Methods. We performed a cross sectional analysis comparing 39 HCV(+) with 60 HCV(-) OLT recipients. IR and beta-cell function were calculated using validated measures and were correlated with clinical variables. Results. By multivariate analysis of the entire cohort, HCV infection and body mass index (BMI) were independent predictors of IR (P=0.04 and 0.0006, respectively). HCV infection was associated with 35% increase in IR. Because the model used to calculate IR was derived from nondiabetic subjects, we performed additional analysis of patients who did not meet criteria for diabetes at the time of their study evaluation. In this analysis, HCV(+) subjects had greater fasting insulin and homeostasis model assessment (HOMA) IR (15.3 mu U/mL and 3.8) compared with HCV(-) patients (10.7 mu U/mL and 2.5) (P=0.03, 0.03). There was no difference in beta-cell function or hepatic insulin extraction between the HCV (+) and (-) groups. HCV (P=0.0005), BMI (P < 0.0001), and high high-density lipoprotein (P=0.039) were the only independent predictors of IR. The presence of HCV infection and a 10-fold increase in HCV RNA were associated with a 62% and 8% increase in IR, respectively. Conclusions. HCV is independently associated with increased IR after OLT. These findings provide a possible pathogenetic HCV. C1 Massachusetts Gen Hosp, GI Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, Dept Med, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [T32 DK07477, R01 DK57857] NR 35 TC 78 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 2004 VL 77 IS 5 BP 703 EP 710 DI 10.1097/01.TP.0000114283.04840.3A PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 804UN UT WOS:000220323700012 PM 15021833 ER PT J AU Hess, C Altfeld, M Thomas, SY Addo, MM Rosenberg, ES Allen, TM Draenert, R Eldrige, RL van Lunzen, J Stellbrink, HJ Walker, BD Luster, AD AF Hess, C Altfeld, M Thomas, SY Addo, MM Rosenberg, ES Allen, TM Draenert, R Eldrige, RL van Lunzen, J Stellbrink, HJ Walker, BD Luster, AD TI HIV-1 specific CD8+T cells with an effector phenotype and control of viral replication SO LANCET LA English DT Article ID T-LYMPHOCYTES AB Most people infected with HIV-1 cannot control viral replication despite the presence of virus-specific CD8+ T cells. It has been postulated that this inability is related to the failure of these cells to mature into fully differentiated effector cells. We tested this hypothesis by comparing the maturation phenotype of virus-specific CD8+ T cells in people who could control viral replication off anti-retroviral therapy with those who could not; In five patients with treated acute HIV-1-infection, structured treatment interruption (STI) induced control of viral replication was associated with expansion of virus-specific CD8+ T cells with a fully differentiated effector phenotype. These effector cells were also expanded in treatment-naive chronically infected individuals who spontaneously controlled viral replication, and augmented expression of perforin was noted in both settings. Our data show that full maturation of virus-specific CD8+ T cells is possible in the context of HIV-1-infection, and suggest that such maturation might be important in viral control. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Cambridge, MA 02138 USA. Univ Hamburg, Hosp Eppendorf, Infect Dis Outpatient Clin, Hamburg, Germany. RP Luster, AD (reprint author), Massachusetts Gen Hosp E, Bldg 149,13th St, Charlestown, MA 02482 USA. EM luster@helix.mgh.harvard.edu RI Allen, Todd/F-5473-2011; OI Thomas, Seddon/0000-0003-0075-0744 NR 5 TC 80 Z9 84 U1 1 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 13 PY 2004 VL 363 IS 9412 BP 863 EP 866 DI 10.1016/S0140-6736(04)15735-8 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 803LB UT WOS:000220231500014 PM 15031033 ER PT J AU Yu, LQ Frith, MC Suzuki, Y Peterfreund, RA Gearan, T Sugano, S Schwarzschild, MA Weng, ZP Fink, JS Chen, JF AF Yu, LQ Frith, MC Suzuki, Y Peterfreund, RA Gearan, T Sugano, S Schwarzschild, MA Weng, ZP Fink, JS Chen, JF TI Characterization of genomic organization of the adenosine A(2A) receptor gene by molecular and bioinformatics analyses SO BRAIN RESEARCH LA English DT Article DE adenosine A(2A) receptor; 5 '-UTR; alternative promoter; multiple transcription start site ID EUKARYOTIC MESSENGER-RNAS; IN-SITU HYBRIDIZATION; UNTRANSLATED REGIONS; ALTERNATIVE PROMOTERS; HUNTINGTONS-DISEASE; PARKINSONS-DISEASE; MULTIPLE PROMOTERS; HUMAN BRAIN; EXPRESSION; TRANSLATION AB The adenosine A(2A) receptor (A(2A)R) is abundantly expressed in brain and emerging as an important therapeutic target for Parkinson's disease and potentially other neuropsychiatric disorders. To understand the molecular mechanisms of A(2A)R gene expression, we have characterized the genomic organization of the mouse and human A(2A)R genes by molecular and bioinformatic analyses. Three new exons (rnlA, mlB and mlC) encoding the 5' untranslated regions (5'-UTRs) Of Mouse A(2A)R mRNA were identified by rapid amplification of 5' cDNA end (5' RACE), RT-PCR analysis and genome sequence analyses. Similar bioinformatics analysis also suggested six variants of the non-coding "exon 1" (h1A, h 1B, h1C, h1D, h1E and h1F) in the human A(2A)R gene. which were confirmed by RT-PCR analysis, while three of the human exon 1 variants (h1D, h1E and h1F) were likewise verified by 5' oligonucleotide capping analysis Suggesting multiple transcription start sites. Importantly, RT-PCR and quantitative PCR analysis demonstrated that the A(2A)R transcripts with different exon I variants displayed tissue-specific expression patterns. For instance, the mouse exon m1A mRNA was detected only in brain (specifically striatum) and the human exon h1D mRNA in lymphoreticular system. Furthermore, the determination of the three new transcription start sites of human A(2A)R gene by 5' oligonucleotide capping and bioinformatics analyses led to the identification of three corresponding promoter regions which contain several important cis elements, providing additional target for further molecular dissection of A(2A)R gene expression. Finally, Our analysis indicates that A(2A)R mRNA and a novel transcript partially overlapping with the 3' exon h3, but in opposite orientation to the A(2A)R gene, could conceivably form duplexes to mutually regulate transcript expression. Thus, combined molecular and bioinformatics analyses revealed a new A(2A)R genomic structure, with conserved coding exons 2 and 3 and divergent, tissue-specific exon 1 variants encoding for 5' -UTR. This raises the possibility of generating multiple tissue-specific A(2A)R mRNA species by alternative promoters with varying regulatory susceptibility. (C) 2004 Elsevier B.V. All rights reserved. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biomed Engn, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02139 USA. Massachusetts Gen Hosp, Dept Anesthesia, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. Univ Tokyo, Inst Med Sci, Human Genome Ctr, Lab Genome Struct Anal,Minato Ku, Tokyo 1088639, Japan. Boston Univ, Bioinformat Program, Boston, MA 02118 USA. RP Chen, JF (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,C329, Boston, MA 02118 USA. EM chenjf@bu.edu OI Frith, Martin/0000-0003-0998-2859 FU NINDS NIH HHS [NS41083, NS37403] NR 79 TC 37 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 12 PY 2004 VL 1000 IS 1-2 BP 156 EP 173 DI 10.1016/j.brainres.2003.11.072 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 813DP UT WOS:000220888100018 PM 15053963 ER PT J AU Luo, BH Takagi, J Springer, TA AF Luo, BH Takagi, J Springer, TA TI Locking the beta(3) integrin I-like domain into high and low affinity conformations with disulfides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; A-DOMAIN; EXTRACELLULAR SEGMENT; SUBUNIT; PROTEIN; LIGAND; ACTIVATION; COMPLEX; ALPHA(5)BETA(1); ALPHA-L-BETA-2 AB Although integrin alpha subunit I domains exist in multiple conformations, it is controversial whether integrin beta subunit I-like domains undergo structurally analogous movements of the alpha7-helix that are linked to affinity for ligand. Disulfide bonds were introduced into the beta(3) integrin I-like domain to lock its beta6-alpha7 loop and alpha7-helix in two distinct conformations. Soluble ligand binding, ligand mimetic mAb binding and cell adhesion studies showed that disulfide-bonded receptor alpha(IIbbeta3)(T329C/A347C) was locked in a low affinity state, and dithiothreitol treatment restored the capability of being activated to high affinity binding; by contrast, disulfide-bonded alpha(IIb)beta3(V332C/M335C) was locked in a high affinity state. The results suggest that activation of the beta subunit I-like domain is analogous to that of the alpha subunit I domain, i.e. that axial movement in the C-terminal direction of the alpha7-helix is linked to rearrangement of the I-like domain metal ion-dependent adhesion site into a high affinity conformation. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NHLBI NIH HHS [HL48675] NR 29 TC 75 Z9 76 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 MAR 12 PY 2004 VL 279 IS 11 BP 10215 EP 10221 DI 10.1074/jbc.M312732200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400068 PM 14681220 ER PT J AU Medeiros, LA Khan, T El Khoury, JB Pham, CLL Hatters, DM Howlett, GJ Lopez, R O'Brien, KD Moore, KJ AF Medeiros, LA Khan, T El Khoury, JB Pham, CLL Hatters, DM Howlett, GJ Lopez, R O'Brien, KD Moore, KJ TI Fibrillar amyloid protein present in atheroma activates CD36 signal transduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APOLIPOPROTEIN-C-II; SCAVENGER RECEPTOR CD36; LOW-DENSITY-LIPOPROTEIN; ALZHEIMERS-DISEASE; ATHEROSCLEROTIC PLAQUES; A-IV; BETA; CHOLESTEROL; MACROPHAGES; MECHANISMS AB The self-association of proteins to form amyloid fibrils has been implicated in the pathogenesis of a number of diseases including Alzheimer's, Parkinson's, and Creutzfeldt-Jakob diseases. We recently reported that the myeloid scavenger receptor CD36 initiates a signaling cascade upon binding to fibrillar beta-amyloid that stimulates recruitment of microglia in the brain and production of inflammatory mediators. This receptor plays a key role in the pathogenesis of atherosclerosis, prompting us to evaluate whether fibrillar proteins were present in atherosclerotic lesions that could initiate signaling via CD36. We show that apolipoprotein C-II, a component of very low and high density lipoproteins, readily forms amyloid fibrils that initiate macrophage inflammatory responses including reactive oxygen production and tumor necrosis factor alpha expression. Using macrophages derived from wild type and Cd36(-/-) mice to distinguish CD36-specific events, we show that fibrillar apolipoprotein C-II activates a signaling cascade downstream of this receptor that includes Lyn and p44/42 MAPKs. Interruption of this signaling pathway through targeted deletion of Cd36 or blocking of p44/42 MAPK activation inhibits macrophage tumor necrosis factor alpha gene expression. Finally, we demonstrate that apolipoprotein C-II in human atheroma co-localizes to regions positive for markers of amyloid and macrophage accumulation. Together, these data characterize a CD36-dependent signaling cascade initiated by fibrillar amyloid species that may promote atherogenesis. C1 Harvard Univ, Sch Med, Lipid Metab Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Melbourne, Vic 3010, Australia. RP Moore, KJ (reprint author), Harvard Univ, Sch Med, Lipid Metab Unit, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM kmoore@molbio.mgh.harvard.edu OI Hatters, Danny/0000-0002-9965-2847; Moore, kathryn/0000-0003-2505-2547 FU NIA NIH HHS [R01AG/HL20255]; NINDS NIH HHS [NS41330-3] NR 42 TC 96 Z9 98 U1 1 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 MAR 12 PY 2004 VL 279 IS 11 BP 10643 EP 10648 DI 10.1074/jbc.M311735200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400118 PM 14699114 ER PT J AU Abdollahi, A Hahnfeldt, P Maercker, C Grone, HJ Debus, J Ansorge, W Folkman, J Hlatky, L Huber, PE AF Abdollahi, A Hahnfeldt, P Maercker, C Grone, HJ Debus, J Ansorge, W Folkman, J Hlatky, L Huber, PE TI Endostatin's antiangiogenic signaling network SO MOLECULAR CELL LA English DT Article ID NF-KAPPA-B; HUMAN ENDOTHELIAL-CELLS; TUMOR-GROWTH; GENE-EXPRESSION; MATRIX METALLOPROTEINASES; ANGIOGENESIS INHIBITION; REGULATES ANGIOGENESIS; BREAST-CANCER; TISSUE FACTOR; DNA-BINDING AB It is here demonstrated that the set of gene expressions underlying the angiogenic balance in tissues can be molecularly reset en masse by a single protein. Using genome-wide expression profiling, coupled with RT-PCR and phosphorylation analysis, we show that the endogenous angiogenesis inhibitor endostatin down-regulates many signaling pathways in human microvascular endothelium associated with proangiogenic activity. Simultaneously, endostatin is found to upregulate many antiangiogenic genes. The result is a unique alignment between the direction of gene regulation and angiogenic status. Profiling further reveals the regulation of genes not heretofore associated with angiogenesis. Our analysis of coregulated genes shows complex interpathway communications in an intricate signaling network that both recapitulates and extends on current understanding of the angiogenic process. More generally, insights into the nature of genetic networking from the cell biologic and therapeutic perspectives are revealed. C1 Univ Heidelberg, Sch Med, Dept Radiat Oncol, German Canc Res Ctr, Heidelberg, Germany. Univ Heidelberg, Sch Med, Dept Radiat Oncol, Heidelberg, Germany. Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA USA. German Genome Resource Ctr, Berlin, Germany. German Canc Res Ctr, Dept Mol Pathol, D-6900 Heidelberg, Germany. European Mol Biol Lab, Heidelberg, Germany. Harvard Univ, Sch Med, Surg Res Lab, Dept Surg,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Huber, PE (reprint author), Univ Heidelberg, Sch Med, Dept Radiat Oncol, German Canc Res Ctr, Bergheimer Str 58, Heidelberg, Germany. EM p.huber@dkfz.de FU NCI NIH HHS [CA86302, CA64481, CA78496] NR 75 TC 282 Z9 308 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 12 PY 2004 VL 13 IS 5 BP 649 EP 663 DI 10.1016/S1097-2765(04)00102-9 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 803CK UT WOS:000220209000004 PM 15023336 ER PT J AU Rosowsky, A Forsch, RA Sibley, CH Inderlied, CB Queener, SF AF Rosowsky, A Forsch, RA Sibley, CH Inderlied, CB Queener, SF TI New 2,4-diamino-5-(2 ',5 '-substituted benzyl)pyrimidines as potential drugs against opportunistic infections of AIDS and other immune disorders. Synthesis and species-dependent antifolate activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MYCOBACTERIUM-AVIUM COMPLEX; DIHYDROFOLATE-REDUCTASE INHIBITORS; PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII; IN-VITRO; TRIMETHOPRIM; IDENTIFICATION; PYRIMETHAMINE; COMBINATION AB In a continuing effort to design small-molecule inhibitors of dihydrofolate reductase (DHFR) that combine the enzyme-binding selectivity of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine (trimethoprim, TMP) with the potency of 2,4-diamino-5-methyl-6-(2',5'-dimethoxybenzyl)pyrido[2,3-d]pyrimidine (piritrexim, PTX), seven previously undescribed 2,4-diamino5-[2'-methoxy-5'-(substituted benzyl)]pyrimidines were synthesized in which the substituent at the 5'-position was a carboxyphenyl group linked to the benzyl moiety by a bridge of two or four atoms in length. The new analogues were all obtained from 2+diamino-5-(5'-iodo-2'methoxybenzyl)pyrimidine via a Sonogashira reaction, followed, where appropriate, by catalytic hydrogenation. The new analogues were tested as inhibitors of DHFR from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three life-threatening pathogens often found in AIDS patients and individuals whose immune system is impaired as a result of treatment with immunosuppressive chemotherapy or radiation. The selectivity index (SI) of each compound was obtained by dividing its 50% inhibitory concentration (IC50) against Pc, Tg, or Ma DHFR by its IC50 against rat DHFR. 2,4-Diamino-[2'-methoxy-5'-(3-carboxyphenyl)ethynylbenzyl]pyrimidine (28), with an IC50 of 23 nM and an SI of 28 in the Pc DHFR assay, had about the same potency as PTX and was 520 times more potent than TMP. As an inhibitor of Tg DHFR, 28 had an IC50 of 5.5 nM (510-fold lower than that of TMP and similar to that of PTX) and an SI value of 120 (2-fold better than TMP and vastly superior to PTX). Against Ma DHFR, 28 had IC50 and SI values of 1.5 nM and 430, respectively, compared with 300 nM and 610 for TMP. Although it had 2.5-fold lower potency than 28 against Ma DHFR (IC50 = 3.7 nM) and was substantially weaker against Pc and Tg DHFR, 2,4-diamino-[2'-methoxy-5'-(4-carboxyphenyl)ethynylbenzyl]pyrimidine (29), with the carboxy group at the para rather than the meta position, displayed 2200-fold selectivity against the Ma enzyme and was the most selective 2,4-diamino-5-(5'-substituted benzyl)pyrimidine inhibitor of this enzyme we have encountered to date. Additional bioassay data for these compounds are also reported. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. RP Rosowsky, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM andre_rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI55064, R01-AI29904] NR 25 TC 27 Z9 28 U1 0 U2 1 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 MAR 11 PY 2004 VL 47 IS 6 BP 1475 EP 1486 DI 10.1021/jm030438k PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 800OX UT WOS:000220038700018 PM 14998335 ER PT J AU Koike, N Fukumura, D Gralla, O Au, P Schechner, JS Jain, RK AF Koike, N Fukumura, D Gralla, O Au, P Schechner, JS Jain, RK TI Creation of long-lasting blood vessels SO NATURE LA English DT Editorial Material ID IN-VIVO; CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06520 USA. RP Koike, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 10 TC 371 Z9 387 U1 3 U2 45 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2004 VL 428 IS 6979 BP 138 EP 139 DI 10.1038/428138a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 801NW UT WOS:000220103600033 PM 15014486 ER PT J AU Johnson, J Canning, J Kaneko, T Pru, JK Tilly, JL AF Johnson, J Canning, J Kaneko, T Pru, JK Tilly, JL TI Germline stem cells and follicular renewal in the postnatal mammalian ovary SO NATURE LA English DT Article ID MEIOTIC RECOMBINATION; PRIMORDIAL FOLLICLES; HOMING EFFICIENCY; GENE-EXPRESSION; MICE; MOUSE; PROTEIN; TRANSPLANTATION; APOPTOSIS; PROPHASE AB A basic doctrine of reproductive biology is that most mammalian females lose the capacity for germ-cell renewal during fetal life, such that a fixed reserve of germ cells (oocytes) enclosed within follicles is endowed at birth. Here we show that juvenile and adult mouse ovaries possess mitotically active germ cells that, based on rates of oocyte degeneration (atresia) and clearance, are needed to continuously replenish the follicle pool. Consistent with this, treatment of prepubertal female mice with the mitotic germ-cell toxicant busulphan eliminates the primordial follicle reserve by early adulthood without inducing atresia. Furthermore, we demonstrate cells expressing the meiotic entry marker synaptonemal complex protein 3 in juvenile and adult mouse ovaries. Wild-type ovaries grafted into transgenic female mice with ubiquitous expression of green fluorescent protein (GFP) become infiltrated with GFP-positive germ cells that form follicles. Collectively, these data establish the existence of proliferative germ cells that sustain oocyte and follicle production in the postnatal mammalian ovary. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. EM jtilly@partners.org NR 50 TC 612 Z9 657 U1 16 U2 87 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2004 VL 428 IS 6979 BP 145 EP 150 DI 10.1038/nature02316 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 801NW UT WOS:000220103600039 PM 15014492 ER PT J AU Wei, W Ayad, NG Wan, Y Zhang, GJ Kirschner, MW Kaelin, WG AF Wei, W Ayad, NG Wan, Y Zhang, GJ Kirschner, MW Kaelin, WG TI Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex SO NATURE LA English DT Article ID BOX PROTEIN SKP2; DNA-REPLICATION; S-PHASE; MITOSIS; PROTEOLYSIS; RECOGNITION; EXPRESSION; P27(KIP1); BINDING; DESTRUCTION AB Cell-cycle transitions are driven by waves of ubiquitin-dependent degradation of key cell-cycle regulators. SCF (Skp1/Cullin/F-box protein) complexes and anaphase-promoting complexes (APC) represent two major classes of ubiquitin ligases whose activities are thought to regulate primarily the G1/S and metaphase/anaphase cell-cycle transitions, respectively(1,2). The major target of the Skp1/Cul1/Skp2 (SCFSKP2) complex is thought to be the Cdk inhibitor p27 during S phase, whereas the principal targets for the APC are thought to be involved in chromatid separation (securin) and exit from mitosis (cyclin B). Although the role of the APC in mitosis is relatively clear, there is mounting evidence that APCs containing Cdh1 (APC(CDH1)) also have a function in the G1 phase of the cell cycle(2,3). Here, we show that the F-box protein Skp2 is polyubiquitinated, and hence earmarked for destruction, by APC(CDH1). As a result, accumulation of SCFSKP2 requires prior inactivation of APC(CDH1). These findings provide an insight into the orchestration of SCF and APC activities during cell-cycle progression, and into the involvement of the APC in G1. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kirschner, MW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM marc@hms.harvard.edu; william_kaelin@dfci.harvard.edu RI Zhang, Guo-Jun/H-3890-2015 OI Zhang, Guo-Jun/0000-0001-5182-5887 NR 30 TC 296 Z9 307 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2004 VL 428 IS 6979 BP 194 EP 198 DI 10.1038/nature02381 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 801NW UT WOS:000220103600052 PM 15014503 ER PT J AU Choi, HK Atkinson, K Karlson, EW Willett, W Curhan, G AF Choi, HK Atkinson, K Karlson, EW Willett, W Curhan, G TI Purine-rich foods, dairy and protein intake, and the risk of gout in men SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; URIC-ACID METABOLISM; FREQUENCY QUESTIONNAIRE; ELDERLY-MEN; WOMEN; SERUM; REPRODUCIBILITY; VALIDITY; HYPERURICEMIA; HEALTH AB BACKGROUND: Various purine-rich foods and high protein intake have long been thought to be risk factors for gout. Similarly, the possibility that the consumption of dairy products has a role in protecting against gout has been raised by metabolic studies. We prospectively investigated the association of these dietary factors with new cases of gout. METHODS: Over a 12-year period, we prospectively examined the relationship between purported dietary risk factors and new cases of gout among 47,150 men who had no history of gout at base line. We used a supplementary questionnaire to ascertain whether participants met the American College of Rheumatology survey criteria for gout. Diet was assessed every four years by means of a food-frequency questionnaire. RESULTS: During the 12 years of the study, we documented 730 confirmed new cases of gout. The multivariate relative risk of gout among men in the highest quintile of meat intake, as compared with those in the lowest quintile, was 1.41 (95 percent confidence interval, 1.07 to 1.86; P for trend = 0.02), and the corresponding relative risk associated with seafood intake was 1.51 (95 percent confidence interval, 1.17 to 1.95; P for trend = 0.02). In contrast, the incidence of gout decreased with increasing intake of dairy products; the multivariate relative risk among men in the highest quintile, as compared with those in the lowest quintile, was 0.56 (95 percent confidence interval, 0.42 to 0.74; P for trend <0.001). The level of consumption of purine-rich vegetables and the total protein intake were not associated with an increased risk of gout. CONCLUSIONS: Higher levels of meat and seafood consumption are associated with an increased risk of gout, whereas a higher level of consumption of dairy products is associated with a decreased risk. Moderate intake of purine-rich vegetables or protein is not associated with an increased risk of gout. C1 Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK58573] NR 35 TC 374 Z9 408 U1 14 U2 52 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAR 11 PY 2004 VL 350 IS 11 BP 1093 EP 1103 DI 10.1056/NEJMoa035700 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 801QJ UT WOS:000220110100006 PM 15014182 ER PT J AU Brugge, WR Bounds, BC Harris, NL Cohen, A Misdraji, J Kotton, CN AF Brugge, WR Bounds, BC Harris, NL Cohen, A Misdraji, J Kotton, CN TI A 28-year-old man with abdominal pain, fever, and a mass in the region of the pancreas. Tuberculous lymphadenitis involving the peripancreatic lymph nodes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SOLID-PSEUDOPAPILLARY TUMOR; MUCINOUS CYSTIC TUMORS; RARE CAUSE; OBSTRUCTIVE-JAUNDICE; FEATURES; INFECTIONS; MIMICKING; MARKERS C1 Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. NR 33 TC 9 Z9 11 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 MAR 11 PY 2004 VL 350 IS 11 BP 1131 EP 1138 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 801QJ UT WOS:000220110100012 PM 15014187 ER PT J AU Matthews, AGW Elkin, SK Oettinger, MA AF Matthews, AGW Elkin, SK Oettinger, MA TI Ordered DNA release and target capture in RAG transposition SO EMBO JOURNAL LA English DT Article DE pathway; RAG; V(D)J recombination; target capture; transposition ID SINGLE ACTIVE-SITE; C-TERMINAL REGION; V(D)J RECOMBINATION; SYNAPTIC COMPLEX; IMMUNE-SYSTEM; CLEAVAGE; PROTEINS; RESIDUES; STEPS; COMPARTMENTALIZATION AB Following V(D)J cleavage, the newly liberated DNA signal ends can be either fused together into a signal joint or used as donor DNA in RAG-mediated transposition. We find that both V(D)J cleavage and release of flanking coding DNA occur before the target capture step of transposition can proceed; no coding DNA is ever detected in the target capture complex. Separately from its role in V(D)J cleavage, the DDE motif of the RAG1/2 active site is specifically required for target DNA capture. The requirement for cleavage and release of coding DNA prior to either physical target binding or functional target commitment suggests that the RAG1/2 transposase contains a single binding site for non-RSS DNA that can accommodate either target DNA or coding DNA, but not both together. Perhaps the presence of coding DNA may aid in preventing transpositional resolution of V(D)J recombination intermediates. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Oettinger, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, 10th Floor,50 Blossom St, Boston, MA 02114 USA. EM oettinger@frodo.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM048026, R01GM48026] NR 36 TC 13 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 10 PY 2004 VL 23 IS 5 BP 1198 EP 1206 DI 10.1038/sj.emboj.7600131 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810HA UT WOS:000220694200020 PM 14988730 ER PT J AU Bassik, MC Scorrano, L Oakes, SA Pozzan, T Korsmeyer, SJ AF Bassik, MC Scorrano, L Oakes, SA Pozzan, T Korsmeyer, SJ TI Phosphorylation of BCL-2 regulates ER Ca2+ homeostasis and apoptosis SO EMBO JOURNAL LA English DT Article DE apoptosis; BCL-2; calcium; endoplasmic reticulum; phosphorylation ID MITOCHONDRIAL PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM; PROTEIN-KINASE; CELL-DEATH; CANCER-CELLS; CYTOCHROME-C; BAX; COMPLEX; DOMAIN; INTERLEUKIN-3 AB Phosphorylation of BCL-2 within an unstructured loop inhibits its antiapoptotic effect. We found that phosphorylated BCL-2 predominantly localized to the endoplasmic reticulurn (ER) and tested whether phosphorylation would control its activity at this organelle, where Ca2+ dynamics serve as a critical control point for apoptosis. Phosphorylation greatly inhibits the ability of BCL-2 to lower [Ca2+](er) and protect against Ca2+-dependent death stimuli. Cells expressing nonphosphorylatable BCL-2(AAA) exhibited increased leak of Ca2+ from the ER and further diminished steady-state [Ca2+](er) stores when compared to cells expressing BCL-2(wt). Consequently, when BCL-2 is phosphorylated, Ca2+ discharge from the ER is increased, with a secondary increase in mitochondrial Ca2+ uptake. We also demonstrate that phosphorylation of BCL-2 inhibits its binding to proapoptotic family members. This inhibitory mechanism manifested at the ER, where phosphorylated BCL-2 was unable to bind proapoptotic members. [Ca2+](er) proved coordinate with the capacity of BCL-2 to bind proapoptotic BH3-only members, further integrating the apoptotic pathway and Ca2+ modulation. Unexpectedly, the regulation of ER Ca2+ dynamics is a principal avenue whereby BCL-2 phosphorylation alters susceptibility to apoptosis. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA 02115 USA. Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. Univ Padua, Dept Biomed Sci, Padua, Italy. RP Korsmeyer, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, 44 Binney St, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [R37 CA050239, R37CA50239, T32 CA009361, T32 CA09361]; Telethon [TCP02016] NR 46 TC 181 Z9 184 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 10 PY 2004 VL 23 IS 5 BP 1207 EP 1216 DI 10.1038/sj.emboj.7600104 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810HA UT WOS:000220694200021 PM 15010700 ER PT J AU Denys, K Vanduffel, W Fize, D Nelissen, K Peuskens, H Van Essen, D Orban, GA AF Denys, K Vanduffel, W Fize, D Nelissen, K Peuskens, H Van Essen, D Orban, GA TI The processing of visual shape in the cerebral cortex of human and nonhuman primates: A functional magnetic resonance imaging study SO JOURNAL OF NEUROSCIENCE LA English DT Article DE visual cortex; functional imaging; object processing; monkey; homology; cue invariance ID INFERIOR TEMPORAL NEURONS; HUMAN OCCIPITAL LOBE; INFEROTEMPORAL CORTEX; INTRAPARIETAL CORTEX; SURFACE ORIENTATION; MACAQUE MONKEY; CONTRAST AGENT; OBJECT SHAPE; DORSAL V4; MOTION AB We compared neural substrates of two-dimensional shape processing in human and nonhuman primates using functional magnetic resonance (MR) imaging in awake subjects. The comparison of MR activity evoked by viewing intact and scrambled images of objects revealed shape-sensitive regions in occipital, temporal, and parietal cortex of both humans and macaques. Intraparietal cortex in monkeys was relatively more two-dimensional shape sensitive than that of humans. In both species, there was an interaction between scrambling and type of stimuli (grayscale images and drawings), but the effect of stimulus type was much stronger in monkeys than in humans. Shape- and motion-sensitive regions overlapped to some degree. However, this overlap was much more marked in humans than in monkeys. The shape-sensitive regions can be used to constrain the warping of monkey to human cortex and suggest a large expansion of lateral parietal and superior temporal cortex in humans compared with monkeys. C1 Katholieke Univ Leuven, Neuro & Psychofysiol Lab, Sch Med, B-3000 Louvain, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Orban, GA (reprint author), Katholieke Univ Leuven, Neuro & Psychofysiol Lab, Sch Med, Campus Gasthuisberg,Herestr 49, B-3000 Louvain, Belgium. EM guy.orban@med.kuleuven.ac.be RI Fize, Denis/F-4525-2011 FU NIMH NIH HHS [R01 MH60974] NR 63 TC 146 Z9 146 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 MAR 10 PY 2004 VL 24 IS 10 BP 2551 EP 2565 DI 10.1523/JNEUROSCI.3569-03.2004 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 801XY UT WOS:000220129800023 PM 15014131 ER PT J AU Shaw, RJ Kosmatka, M Bardeesy, N Hurley, RL Witters, LA DePinho, RA Cantley, LC AF Shaw, RJ Kosmatka, M Bardeesy, N Hurley, RL Witters, LA DePinho, RA Cantley, LC TI The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT PROTEIN-KINASE; SKELETAL-MUSCLE; GLUCOSE-METABOLISM; UPSTREAM KINASES; CELL-GROWTH; SURVIVAL; COMPLEX; TRANSFORMATION; IDENTIFICATION; INHIBITION AB AMP-activated protein kinase (AMPK) is a highly conserved sensor of cellular energy status found in all eukaryotic cells. AMPK is activated by stimuli that increase the cellular AMP/ATP ratio. Essential to activation of AMPK is its phosphorylation at Thr-172 by an upstream kinase, AMPKK, whose identity in mammalian cells has remained elusive. Here we present biochemical and genetic evidence indicating that the LKB1 serine/threonine kinase, the gene inactivated in the Peutz-Jeghers familial cancer syndrome, is the dominant regulator of AMPIK activation in several mammalian cell types. We show that LKB1 directly phosphorylates Thr-172 of AMPKalpha in vitro and activates its kinase activity. LKB1-deficient murine embryonic fibroblasts show nearly complete loss of Thr-172 phosphorylation and downstream AMPK signaling in response to a variety of stimuli that activate AMPK. Reintroduction of WT, but not kinase-dead, LKB1 into these cells restores AMPK activity. Furthermore, we show that LKB1 plays a biologically significant role in this pathway, because LKB1-deficient cells are hypersensitive to apoptosis induced by energy stress. On the basis of these results, we propose a model to explain the apparent paradox that LKB1 is a tumor suppressor, yet cells lacking LKB1 are resistant to cell transformation by conventional oncogenes and are sensitive to killing in response to agents that elevate AMP. The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. RP Cantley, LC (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02215 USA. EM lewis.cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; Niles, Rebecca/0000-0001-8568-3047 FU NCI NIH HHS [P01 CA089021, P01CA89021]; NIDDK NIH HHS [R01 DK035712, DK35712]; NIGMS NIH HHS [R01 GM056203, R01 GM56203] NR 39 TC 896 Z9 921 U1 8 U2 46 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 MAR 9 PY 2004 VL 101 IS 10 BP 3329 EP 3335 DI 10.1073/pnas.0308061100 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802LA UT WOS:000220163800003 PM 14985505 ER PT J AU Wexler, NS AF Wexler, NS CA US Venezuala Collaborative Res TI Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRINUCLEOTIDE REPEAT; CAG REPEAT; ASSOCIATION; EXPANSION; FEATURES; LENGTH AB Huntington's disease (HID) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HID, although substantial variability remains after controlling for repeat length. The Venezuelan HID kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HID kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximate to40% of the variance remaining in onset age is attributable to genes other than the HID gene and 60% is environmental. C1 Columbia Univ, New York, NY 10032 USA. Univ Ulm, D-89069 Ulm, Germany. Albany Med Coll, Albany, NY 12208 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. CUNY, New York, NY 10016 USA. Univ Iowa, Iowa City, IA 52242 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Alabama, Birmingham, AL 35294 USA. Univ Calif Irvine, Irvine, CA 92697 USA. NINDS, NIH, Bethesda, MD 20892 USA. NYU, New York, NY 10016 USA. Hlth & Human Serv Agcy, San Diego, CA 92102 USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Univ So Calif, Los Angeles, CA 90089 USA. N Shore Univ Hosp, Manhasset, NY 11030 USA. Miami Childrens Hosp, Miami, FL 33155 USA. Univ Rochester, Rochester, NY 14620 USA. Univ S Florida, Tampa, FL 33612 USA. Univ Texas, Houston, TX 77030 USA. Hosp Virgen del Camino, Pamplona 31008, Spain. Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. Univ Zulia, Maracaibo 4011, Venezuela. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Indiana Univ, Indianapolis, IN 46202 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Wexler, NS (reprint author), Columbia Univ, 1051 Riverside Dr, New York, NY 10032 USA. EM wexlern@pi.cpmc.columbia.edu RI Cherny, Stacey/B-3315-2008 OI Cherny, Stacey/0000-0002-0269-3352 NR 32 TC 326 Z9 334 U1 4 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 MAR 9 PY 2004 VL 101 IS 10 BP 3498 EP 3503 DI 10.1073/pnas.0308479101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802LA UT WOS:000220163800033 PM 14993615 ER PT J AU Abrahamson, MJ AF Abrahamson, MJ TI Optimal glycemic control in type 2 diabetes mellitus - Fasting and postprandial glucose in context SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; PLASMA-GLUCOSE; BLOOD-GLUCOSE; RISK-FACTOR; MICROVASCULAR COMPLICATIONS; OVERWEIGHT PATIENTS; DOUBLE-BLIND; LIFE-STYLE; HYPERGLYCEMIA AB Type 2 diabetes mellitus is the consequence of both insulin resistance and impaired insulin secretion. In the progression from normal glucose tolerance to diabetes, postprandial glucose (PPG) levels often rise before fasting plasma glucose (FPG) levels increase above 126 mg/dL (7.0 mmol/L). Numerous epidemiologic studies have shown that impaired glucose tolerance is associated with increased risk for macrovascular disease and that isolated postchallenge hyperglycemia is an independent factor for increased mortality. Reducing the risk for microvascular complications by improving glycosylated hemoglobin (HbA(1c)) levels is well documented. Emerging data now support the relationship between glycemic control and macrovascular disease. Epidemiologic studies documenting postprandial hyperglycemia and the risk for increased mortality suggest that lowering PPG levels might be beneficial. Optimizing both FPG and PPG is important in achieving normal/near-normal glucose levels. Many patients with type 2 diabetes have difficulty attaining the recommended HbA(1c) goal despite normal/near-normal FPG levels; thus, pharmacologic treatment targeting PPG levels may prove beneficial. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Abrahamson, MJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl,Room 243, Boston, MA 02215 USA. EM Martin.Abrahamson@joslin.harvard.edu NR 54 TC 22 Z9 24 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 8 PY 2004 VL 164 IS 5 BP 486 EP 491 DI 10.1001/archinte.164.5.486 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 801CN UT WOS:000220074100003 PM 15006824 ER PT J AU McDonald, AJ Wang, N Camargo, CA AF McDonald, AJ Wang, N Camargo, CA TI US emergency department visits for alcohol-related diseases and injuries between 1992 and 2000 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INTERVENTION AB Background: Alcohol-related diseases and injuries pose a significant burden on hospital emergency departments (EDs). Recognized limitations of self-reported data suggest that previous single-year national studies may have underestimated the magnitude of this burden. Methods: Data were obtained from the National Hospital Ambulatory Medical Care Survey for 1992 through 2000. Thirty-seven alcohol-related diagnoses and their corresponding alcohol-attributable fractions (AAFs) were used to estimate the number of ED visits attributable to alcohol. Diagnoses with an AAF of 1 were analyzed by age, sex, and race. Disposition to inpatient settings and alcohol screening also were examined. Results: During these 9 years, there were an estimated 68.6 million (95% confidence interval [CI], 65.6 million to 71.7 million) ED visits attributable to alcohol, a rate of 28.7 (95% CI, 27.1-30.3) per 1000 US population. The number of alcohol-related visits increased 18% during this period. Visit rates for diagnoses with AAFs of I were highest for those who were aged 30 through 49 years, male, and black. From 1992 to 2000, these disparities remained stable for age group but significantly changed for sex (+22%) and race (-76%). Most patients with diagnoses with AAFs of I were not admitted to an inpatient unit, and the percentage of patients who underwent blood alcohol concentration testing was substantially lower than corresponding AAFs. Conclusions: Alcohol-related ED visits are approximately 3 times higher than previous estimates determined by physician documentation or patient disclosure of alcohol involvement. Rising trends, changing disparities, and suboptimal ED management of such visits are a call to action. C1 Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Channing Lab, Sch Med,Dept Med, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. EM emnet@partners.org NR 23 TC 77 Z9 77 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 8 PY 2004 VL 164 IS 5 BP 531 EP 537 DI 10.1001/archinte.164.5.531 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 801CN UT WOS:000220074100009 PM 15006830 ER PT J AU Lathers, DMR Young, MRI AF Lathers, DMR Young, MRI TI Increased aberrance of cytokine expression in plasma of patients with more advanced squamous cell carcinoma of the head and neck SO CYTOKINE LA English DT Article DE cancer; cytokine; HNSCC; Th1; Th2 ID COLONY-STIMULATING FACTOR; IMMUNE SUPPRESSION; PERIPHERAL-BLOOD; CD34(+) CELLS; GENE-THERAPY; IFN-GAMMA; T-CELLS; CANCER; TUMOR; IL-10 AB Patients with head and neck squamous cell carcinoma (HNSCC) are biased toward the Th2 phenotype as they have increased levels of the Th2 cytokines 11-4, IL-6 and IL-10 and diminished levels of the Th1 cytokine IFN-gamma. However, this bias is incomplete since levels of the Th1 cytokines IL-2 and GM-CSF are increased. This study examined the interrelationship among the plasma levels of Th1 and Th2 cytokines in 101 HNSCC patients and 40 age-matched controls without a known malignancy. Control subjects showed extensive interrelationships among levels of IL-1, IL-2, IL-4, and IFN-gamma, as well as between GM-CSF and TGF-beta. HNSCC patients showed an interrelationship in levels of IL-2, IL-4, IFN-gamma and GM-CSF, but to a less significant degree. What was prominent was a decline in correlation among cytokine levels with increased disease burden, such that there were no relationships among any of the cytokines in stage T4 patients. Nodal involvement also was associated with cytokine levels being more independent of each other, although the impact of nodal disease was less prominent than tumor burden. These results show a partial Th2 cytokine bias in HNSCC patients and a progressively more aberrant expression of cytokines with more advanced disease. (C) 2004 Elsevier Ltd. All rights reserved. C1 Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. EM Rita.Young@med.va.gov FU NCI NIH HHS [CA78262, CA79768, CA85266] NR 24 TC 57 Z9 58 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR 7 PY 2004 VL 25 IS 5 BP 220 EP 228 DI 10.1016/j.cyto.2003.11.005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 803HP UT WOS:000220222500004 PM 15036248 ER PT J AU Lange, CG Xu, Z Patterson, BK Medvik, K Harnisch, B Asaad, R Valdez, H Lee, SJ Landay, A Lieberman, J Lederman, MM AF Lange, CG Xu, Z Patterson, BK Medvik, K Harnisch, B Asaad, R Valdez, H Lee, SJ Landay, A Lieberman, J Lederman, MM TI Proliferation responses to HIVp24 during antiretroviral therapy do not reflect improved immune phenotype or function SO AIDS LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; CHRONIC HIV-1 INFECTION; PROLONGED VIRAL SUPPRESSION; LYMPHOCYTE RESPONSES; IMPAIRED FUNCTION; TYPE-1 INFECTION; INDIVIDUALS; ANTIGENS; DISEASE AB Objective: To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses. Methods: HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearson's x(2) analysis. Results: There were no differences between the groups in immune responses to vaccination or in the numbers or phenotype of circulating T cells. In a subgroup of HLA-A2+ or B8+ patients, HIV-reactive CD8+ T cells in both groups had similar expression of perforin, granzyme A and T-cell maturation markers (CD27, CD28, CCR7, CD62L). However, patients with SI > 10 in response to HIVp24 tended to more often have high levels of circulating CD4+ T cells with intracellular HIV-1 mRNA than did patients with SI < 3. Conclusion: Following long-standing suppression of viral replication on ART, the presence of HIV-1 specific T-helper proliferation responses does not correlate with improved indices of immune phenotype or function but may reflect relatively higher levels of HIV-expression. (C) 2004 Lippincott Williams Wilkins. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Ctr AIDS Res, Dept Med,Div Infect Dis, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Sch Med, Chicago, IL 60614 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Rush Med Coll, Chicago, IL 60612 USA. RP Lederman, MM (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Ctr AIDS Res, Dept Med,Div Infect Dis, 2061 Cornell Rd,Room 301 C, Cleveland, OH 44106 USA. EM lederman.michael@clevelandactu.org RI Lange, Christoph/J-6289-2012 FU NIAID NIH HHS [AI 36219, AI 28691, AI 38858, AI 42519, AI 45406] NR 57 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 5 PY 2004 VL 18 IS 4 BP 605 EP 613 DI 10.1097/01.aids.0000111430.91384.68 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809PA UT WOS:000220647400004 PM 15090765 ER PT J AU Li, Q Ren, J Kufe, D AF Li, Q Ren, J Kufe, D TI Interaction of human MUC1 and beta-catenin is regulated by Lck and ZAP-70 in activated Jurkat T cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE MUC1; beta-catenin; Lck; ZAP-70; Jurkat T cells; T cell receptor ID CARCINOMA-ASSOCIATED ANTIGEN; MULTIPLE-MYELOMA CELLS; GROWTH-FACTOR RECEPTOR; TYROSINE PHOSPHORYLATION; CYTOPLASMIC TAIL; C-SRC; PROTEIN; TRANSCRIPTION; DF3; ASSOCIATION AB The MUC1 transmembrane glycoprotein is aberrantly expressed by diverse hematologic malignancies, including those of the T cell lineage. The MUC1 cytoplasmic domain (CD) interacts with beta-catenin; however, the role of MUC1 in T cells is not known. In the present work, MUC1 was studied as a potential downstream effector of the Lck and ZAP-70 tyrosine kinases that are essential for T cell activation. The results demonstrate that anti-CD3-induced or PMA+ionomycin-induced activation of Jurkat T cells is associated with increased binding of MUC1 and Lck. Lck phosphorylates MUC1-CD on Y-46 and, in turn, stimulates the binding of MUC1 to beta-catenin. The results further demonstrate that MUC1 interacts with ZAP-70. In contrast to Lck, ZAP-70 phosphorylates MUC1-CD predominantly on Y-20. However, like Lck, ZAP-70-mediated phosphorylation of MUC1-Y-20 stimulates binding of MUC1 and beta-catenin. These findings indicate that MUC1 functions as a substrate for Lck and ZAP-70 in activated Jurkat T cells and that MUCI integrates T cell receptor signaling with the beta-catenin pathway. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02482 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02482 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA29431, CA42802] NR 35 TC 31 Z9 34 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 5 PY 2004 VL 315 IS 2 BP 471 EP 476 DI 10.1016/j.bbrc.2004.01.075 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 776ZW UT WOS:000189150300032 PM 14766232 ER PT J AU Fuller, RA Westmoreland, SV Ratai, E Greco, JB Kim, JP Lentz, MR He, J Sehgal, PK Masliah, E Halpern, E Lackner, AA Gonzalez, G AF Fuller, RA Westmoreland, SV Ratai, E Greco, JB Kim, JP Lentz, MR He, J Sehgal, PK Masliah, E Halpern, E Lackner, AA Gonzalez, G TI A prospective longitudinal in vivo H-1 MR spectroscopy study of the SIV/macaque model of neuroAIDS SO BMC NEUROSCIENCE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; MAGNETIC-RESONANCE-SPECTROSCOPY; AIDS DEMENTIA COMPLEX; RAPID DISEASE PROGRESSION; CENTRAL-NERVOUS-SYSTEM; HIV-INFECTED PATIENTS; RHESUS MACAQUES; SEROPOSITIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; BRAIN AB Background: The neurological complications of HIV infection remain poorly understood. Clinically, in vivo H-1 magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo H-1 MRS study of the SIV/macaque model of neuroAIDS. Results: Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and H-1 MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time. Conclusions: After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neuroradiol Div, Charlestown, MA USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA. RP Gonzalez, G (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. EM fullerra@umdnj.edu; susan_westmoreland@hms.harvard.edu; ratai@nmr.mgh.harvard.edu; grecoja@grc.nia.nih.gov; jpkim@nmr.mgh.harvard.edu; mlentz@nmr.mgh.harvard.edu; JHE@partners.org; prahbat_seghal@hms.harvard.edu; emasliah@ucsd.edu; elk@mgh-ita.org; alackner@tpc.tulane.edu; rggonzalez@partners.org FU NCRR NIH HHS [RR13213, RR00168-39, P41RR14075, P41 RR014075, K26 RR000168, P51 RR000168]; NIMH NIH HHS [R01 MH061192, MH61192, P50 MH045294]; NINDS NIH HHS [R01 NS034626, R01 NS030769, NS30769, NS34626] NR 42 TC 32 Z9 32 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD MAR 5 PY 2004 VL 5 AR 10 DI 10.1186/1471-2202-5-10 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 817PF UT WOS:000221188700001 PM 15070430 ER PT J AU Xu, YW Moseley, JB Sagot, I Poy, F Pellman, D Goode, BL Eck, MJ AF Xu, YW Moseley, JB Sagot, I Poy, F Pellman, D Goode, BL Eck, MJ TI Crystal structures of a formin homology-2 domain reveal a tethered dimer architecture SO CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; ARP2/3 COMPLEX; BINDING PROTEIN; CELL POLARITY; YEAST; NUCLEATION; PROFILIN; BNI1P; POLYMERIZATION AB Formin proteins participate in a wide range of cytoskeletal processes in all eukaryotes. The defining feature of formins is a highly conserved similar to400 residue region, the Formin Homology-2 (FH2) domain, which has recently been found to nucleate actin filaments' Here we report crystal structures of the S. cerevesiae Bni1p FH2 domain. The mostly alpha-helical FH2 domain forms a unique "tethered dimer" in which two elongated actin binding heads are tied together at either end by an unusual lasso and linker structure. Biochemical and crystallographic observations indicate that the dimer is stable but flexible, with flexibility between the two halves of the dimer conferred by the linker segments. Although each half of the dimer is competent to interact with filament ends, the intact dimer is required for actin nucleation and processive capping. The tethered dimer architecture may allow formins to stair-step on the barbed end of an elongating nascent filament. C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Hematol, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM David_Pellman@dfci.harvard.edu; eck@red.dfci.harvard.edu FU NIGMS NIH HHS [R01 GM061345, GM61345, GM63691] NR 36 TC 219 Z9 223 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 2004 VL 116 IS 5 BP 711 EP 723 DI 10.1016/S0092-8674(04)00210-7 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YQ UT WOS:000221499700011 PM 15006353 ER PT J AU Perez, JM Josephson, L Weissleder, R AF Perez, JM Josephson, L Weissleder, R TI Use of magnetic nanoparticles as nanosensors to probe for molecular interactions SO CHEMBIOCHEM LA English DT Article DE magnetic resonance imaging; molecular recognition; nanosensors; nanostructures; NMR spectroscopy ID QUANTUM DOTS; EXPRESSION; PARTICLES; SPHERES; CANCER; MODEL AB Biocompatible magnetic nanosensors have been designed to detect molecular interactions in biological media. Upon target binding, these nanosensors cause changes in the spin-spin relaxation times of neighboring water molecules, which con be detected by magnetic resonance (NMR/MRI) techniques. These magnetic nanosensors have been designed to detect specific mRNA, proteins, enzymatic activity, and pathogens (e.g., virus) with sensitivity in the low femtomole range (0.5 - 30 fmol). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5404, Charlestown, MA 02129 USA. EM weissleder@helix.myh.harvard.edu FU NCI NIH HHS [CA101781, P50 CA86355] NR 23 TC 169 Z9 179 U1 2 U2 25 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD MAR 5 PY 2004 VL 5 IS 3 BP 261 EP 264 DI 10.1002/cbic.200300730 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 802XS UT WOS:000220196800004 PM 14997516 ER PT J AU Jaffer, FA Weissleder, R AF Jaffer, FA Weissleder, R TI Seeing within - Molecular imaging of the cardiovascular system SO CIRCULATION RESEARCH LA English DT Review DE molecular imaging; atherosclerosis; thrombosis; heart failure; contrast agents ID POSITRON-EMISSION-TOMOGRAPHY; REPORTER GENE-EXPRESSION; SUPERPARAMAGNETIC IRON-OXIDE; MESENCHYMAL STEM-CELLS; HUMAN ATHEROSCLEROTIC PLAQUES; CARDIAC ALLOGRAFT-REJECTION; ACUTE MYOCARDIAL-INFARCTION; TARGETED CONTRAST AGENT; ACTIVATED FACTOR-XIII; IN-VIVO TRACKING AB Molecular imaging is a rapidly evolving discipline with the goal of developing tools to display and quantify molecular and cellular targets in vivo. The heart of this field is based on the rational design and screening of targeted and activatable imaging reporter agents to sense fundamental processes of biology. Parallel advances in small animal imaging systems and in agent synthesis have allowed molecular imaging applications to extend into the in vivo arena. These advances have permitted, for example, in vivo sensing of inflammation, apoptosis, cell trafficking, and gene expression. In this review, we first review core principles of molecular imaging with an emphasis on smart, activatable agent technology. We then discuss applications of state-of-the-art molecular probes to interrogate important aspects of cardiovascular biology, with a focus on atherosclerosis, thrombosis, and heart failure. In the ensuing years, we anticipate that fundamental aspects of cardiovascular biology will be detectable in vivo, and that promising molecular imaging agents will be translated into the clinical arena to guide diagnosis and therapy of human cardiovascular illness. C1 Harvard Univ, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. RP Jaffer, FA (reprint author), Harvard Univ, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Sch Med, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM fjaffer@partners.org; weissleder@helix.mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU NCI NIH HHS [P50-CA86355] NR 148 TC 128 Z9 142 U1 3 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 5 PY 2004 VL 94 IS 4 BP 433 EP 445 DI 10.1161/01.RES.0000119321.18573.5A PG 13 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 800NF UT WOS:000220034300005 PM 15001542 ER PT J AU Torella, D Rota, M Nurzynska, D Musso, E Monsen, A Shiraishi, I Zias, E Walsh, K Rosenzweig, A Sussman, MA Urbanek, K Nadal-Ginard, B Kajstura, J Anversa, P Leri, A AF Torella, D Rota, M Nurzynska, D Musso, E Monsen, A Shiraishi, I Zias, E Walsh, K Rosenzweig, A Sussman, MA Urbanek, K Nadal-Ginard, B Kajstura, J Anversa, P Leri, A TI Cardiac stem cell and myocyte aging, heart failure, and insulin-like growth factor-1 overexpression SO CIRCULATION RESEARCH LA English DT Article DE telomerase; telomere dysfunction; cellular senescence ID TRANSGENIC MICE; SENESCENCE; TELOMERASE; INFARCTION; MECHANISMS; DISEASE; SYSTEM; DEATH; PROLIFERATION; REGENERATION AB To determine whether cellular aging leads to a cardiomyopathy and heart failure, markers of cellular senescence, cell death, telomerase activity, telomere integrity, and cell regeneration were measured in myocytes of aging wild- type mice ( WT). These parameters were similarly studied in insulin- like growth factor- 1 ( IGF- 1) transgenic mice ( TG) because IGF- 1 promotes cell growth and survival and may delay cellular aging. Importantly, the consequences of aging on cardiac stem cell ( CSC) growth and senescence were evaluated. Gene products implicated in growth arrest and senescence, such as p27(Kip1), p53, p16(INK4a), and p19(ARF), were detected in myocytes of young WT mice, and their expression increased with age. IGF- 1 attenuated the levels of these proteins at all ages. Telomerase activity decreased in aging WT myocytes but increased in TG, paralleling the changes in Akt phosphorylation. Reduction in nuclear phospho- Akt and telomerase resulted in telomere shortening and uncapping in WT myocytes. Senescence and death of CSCs increased with age in WT impairing the growth and turnover of cells in the heart. DNA damage and myocyte death exceeded cell formation in old WT, leading to a decreased number of myocytes and heart failure. This did not occur in TG in which CSC- mediated myocyte regeneration compensated for the extent of cell death preventing ventricular dysfunction. IGF- 1 enhanced nuclear phospho- Akt and telomerase delaying cellular aging and death. The differential response of TG mice to chronological age may result from preservation of functional CSCs undergoing myocyte commitment. In conclusion, senescence of CSCs and myocytes conditions the development of an aging myopathy. C1 New York Med Coll, Dept Med, Cardiovasc Res Inst, Valhalla, NY 10595 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. San Diego State Univ, Inst Heart, San Diego, CA 92182 USA. San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. RP Leri, A (reprint author), New York Med Coll, Dept Med, Cardiovasc Res Inst, Vosburgh Pavil,Room 318, Valhalla, NY 10595 USA. EM annarosa_leri@nymc.edu RI Nurzynska, Daria/A-2161-2010; OI Nurzynska, Daria/0000-0003-1092-6168; TORELLA, Daniele/0000-0002-4915-5084; Zias, Elias/0000-0001-6658-4334 FU NHLBI NIH HHS [HL-38132, HL-65573, HL-65577, HL-66923]; NIA NIH HHS [AG-023071, AG-15756, AG-17042] NR 35 TC 323 Z9 345 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 5 PY 2004 VL 94 IS 4 BP 514 EP 524 DI 10.1161/01.RES.0000117306.10142.50 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 800NF UT WOS:000220034300014 PM 14726476 ER PT J AU Lee, JY Kim, JH Hong, SH Lee, JY Cherny, RA Bush, AI Palmiter, RD Koh, JY AF Lee, JY Kim, JH Hong, SH Lee, JY Cherny, RA Bush, AI Palmiter, RD Koh, JY TI Estrogen decreases zinc transporter 3 expression and synaptic vesicle zinc levels in mouse brain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTOCHEMICALLY-REACTIVE ZINC; ALZHEIMERS-DISEASED BRAINS; A-BETA; TRANSGENIC MICE; POSTMENOPAUSAL WOMEN; PRECURSOR PROTEIN; AMYLOID PLAQUES; INDUCTION; DEMENTIA; NEURONS AB Previous studies suggest that female sex hormones modulate synaptic zinc levels, which may influence amyloid plaque formation and Alzheimer's disease progression. We examined the effects of ovariectomy and estrogen supplement on the levels of synaptic zinc and zinc transporter protein Znt3 in the brain. Ovariectomy was performed on 5-month-old mice, and 2 weeks later, pellets containing vehicle, low (0.18 mg/pellet), or high dose (0.72 mg) 17beta-estradiol were implanted. After 4 weeks, animals were decapitated, and blood and brain were collected for analysis. Blood analysis indicated that estrogen implants altered plasma estrogen levels in a dose-dependent manner. Analysis of brain tissue showed that ovariectomy raised hippocampal synaptic vesicle zinc levels, whereas estrogen replacement lowered these zinc levels. Western blots revealed that Znt3 levels in the brain were modulated in parallel with synaptic zinc levels, whereas no change was detected in the levels of Znt3 mRNA, as determined by Northern blot and reverse transcriptase-PCR analysis. However, mRNA levels of the delta subunit of adaptor protein complex (AP)-3, which modulates the level of Znt3 levels, were altered by estrogen depletion or replacement. These data demonstrate that estrogen alters the levels of Znt3 and synaptic vesicle zinc in female mice, probably through changing AP-3 delta expression. Since synaptic zinc may play a key role in neuronal death in acute brain injury as well as in plaque formation in Alzheimer's disease, and since estrogen may be beneficial in both conditions, our results may provide new insights into the effects of estrogen on the brain. C1 Univ Ulsan, Coll Med, Natl Creat Res Initiat Ctr Study Cent Nervous Sys, Seoul 138736, South Korea. Univ Ulsan, Coll Med, Dept Neurol, Seoul 138736, South Korea. Univ Ulsan, Coll Med, Dept Obstet & Gynecol, Seoul 138736, South Korea. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Univ Washington, Dept Biochem, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Koh, JY (reprint author), Univ Ulsan, Coll Med, Natl Creat Res Initiat Ctr Study Cent Nervous Sys, 388-1 Poongnapdong, Seoul 138736, South Korea. EM jkko@www.amc.seoul.kr RI Koh, Jae-Young/C-9014-2011; Lee, Joo-Yong/F-4545-2014; Bush, Ashley/A-1186-2007 OI Koh, Jae-Young/0000-0002-4318-495X; Bush, Ashley/0000-0001-8259-9069 NR 49 TC 54 Z9 58 U1 1 U2 5 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 MAR 5 PY 2004 VL 279 IS 10 BP 8602 EP 8607 DI 10.1074/jbc.M309730200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900011 PM 14681234 ER PT J AU Bisognano, C Kelley, WL Estoppey, T Francois, P Schrenzel, J Li, DM Lew, DP Hooper, DC Cheung, AL Vaudaux, P AF Bisognano, C Kelley, WL Estoppey, T Francois, P Schrenzel, J Li, DM Lew, DP Hooper, DC Cheung, AL Vaudaux, P TI A RecA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBINHIBITORY CONCENTRATIONS; ESCHERICHIA-COLI; DNA-DAMAGE; INCREASED EXPRESSION; BACILLUS-SUBTILIS; EPITHELIAL-CELLS; VIRULENCE GENES; SOS RESPONSE; MURINE MODEL; PROTEINS AB Subinhibitory concentrations of ciprofloxacin (CPX) raise the fibronectin-mediated attachment of fluoroquinolone-resistant Staphylococcus aureus by selectively inducing fnbB coding for one of two fibronectin-binding proteins: FnBPB. To identify candidate regulatory pathway(s) linking drug exposure to up-regulation of fnbB, we disrupted the global response regulators agr, sarA, and recA in the highly quinolone-resistant strain RA1. Whereas agr and sarA mutants of RA1 exposed to CPX still displayed increased adhesion to fibronectin, the CPX-triggered response was abolished in the uvs-568 recA mutant, but was restored following complementation with wild type recA. Steady-state levels of recA and fnbB, but not fnbA, mRNA were co-coordinately increased >3-fold in CPX-exposed strain RA1. Electrophoretic mobility shift assays revealed specific binding of purified S. aureus SOS-repressor LexA to recA and fnbB, but not to fnbA or rpoB promoters. DNase I footprint analysis showed LexA binding overlapping the core promoter elements in fnbB. We conclude that activation of recA and derepression of lexA-regulated genes by CPX may represent a response to drug-induced damage that results in a novel induction of a virulence factor leading to increased bacterial tissue adherence. C1 Univ Hosp, Div Infect Dis, CH-1211 Geneva 14, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Dartmouth Coll, Sch Med, Dept Microbiol, Hanover, NH 03755 USA. RP Kelley, WL (reprint author), Univ Hosp, Div Infect Dis, CH-1211 Geneva 14, Switzerland. EM william.kelley@hcuge.ch FU NIAID NIH HHS [AI23988, AI47441] NR 50 TC 48 Z9 48 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 MAR 5 PY 2004 VL 279 IS 10 BP 9064 EP 9071 DI 10.1074/jbc.M309836200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900067 PM 14699158 ER PT J AU Prasad, A Fernandis, AZ Rao, Y Ganju, RK AF Prasad, A Fernandis, AZ Rao, Y Ganju, RK TI Slit protein-mediated inhibition of CXCR4-induced chemotactic and chemoinvasive signaling pathways in breast cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; ENDOTHELIAL GROWTH-FACTOR; REPULSIVE AXON GUIDANCE; OLFACTORY-BULB AXONS; TYROSINE PHOSPHATASE; MATRIX METALLOPROTEINASES; CHEMOKINE RECEPTORS; ROUNDABOUT RECEPTOR; NIH3T3 FIBROBLASTS; NEURONAL MIGRATION AB Slit, which mediates its function by binding to the Roundabout ( Robo) receptor, has been shown to regulate neuronal and CXCR4-mediated leukocyte migration. Slit-2 was shown to be frequently inactivated in lung and breast cancers because of hypermethylation of its promoter region. Furthermore, the CXCR4/CXCL12 axis has been reported recently to be actively involved in breast cancer metastasis to target organs such as lymph nodes, lung, and bone. In this study, we sought to characterize the effect of Slit ( = Slit-2) on the CXCL12/ CXCR4-mediated metastatic properties of breast cancer cells. We demonstrate here that breast cancer cells and tissues derived from breast cancer patients express Robo 1 and 2 receptors. We also show that Slit treatment inhibits CXCL12/ CXCR4-induced breast cancer cell chemotaxis, chemoinvasion, and adhesion, the fundamental components that promote metastasis. Slit had no significant effect on the CXCL12-induced internalization process of CXCR4. In addition, characterization of signaling events revealed that Slit inhibits CXCL12-induced tyrosine phosphorylation of focal adhesion components such as RAFTK/Pyk2 at residues 580 and 881, focal adhesion kinase at residue 576, and paxillin. We found that Slit also inhibits CXCL12-induced phosphatidylinositol 3-kinase, p44/42 MAP kinase, and metalloproteinase 2 and 9 activities. However, it showed no effect on JNK and p38 MAP kinase activities. To our knowledge, this is the first report to analyze in detail the effect of Slit on breast cancer cell motility as well as its effect on the critical components of the cancer cell chemotactic machinery. Studies of the Slit-Robo complex may foster new anti-chemotactic approaches to block cancer cell metastasis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Ganju, RK (reprint author), Harvard Inst Med, BIDMC, 4 Blackfan Circle,Room 343, Boston, MA 02115 USA. EM rganju@bidmc.harvard.edu RI Fernandis, Aaron/C-3718-2012 NR 66 TC 73 Z9 89 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 2004 VL 279 IS 10 BP 9115 EP 9124 DI 10.1074/jbc.M308083200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900073 PM 14645233 ER PT J AU Bassing, CH Alt, FW AF Bassing, CH Alt, FW TI Molecular biology - Case of mistaken identity SO NATURE LA English DT Editorial Material ID GENOMIC INSTABILITY; TRANSLOCATIONS; RECOMBINASE; BREAKS C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Bassing, CH (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM bassing@cbr.med.harvard.edu; alt@enders.tch.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 2004 VL 428 IS 6978 BP 29 EP 31 DI 10.1038/428029a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 780GK UT WOS:000189363800023 PM 14999268 ER PT J AU Sung, B Wang, GK AF Sung, B Wang, GK TI Peripherally administered amitriptyline derivatives have differential anti-allodynic effects in a rat model of neuropathic pain SO NEUROSCIENCE LETTERS LA English DT Article DE neuropathic pain; mechanical allodynia; amitriptyline hydrochloride; N-methyl amitriptyline; pain ID ANTIDEPRESSANTS; INJECTIONS; BLOCKADE; OPIOIDS AB We assessed if derivatives of amitriptyline could alleviate mechanical allodynia in a rat model of neuropathic pain. N-methyl amitriptyline (NMA), and amitriptyline HCl (AHC) were compared to evaluate the antiallodynic effects produced by systemic and peripheral administration. Under general anesthesia with halothane, neuropathic injury was produced in rats by tightly ligating the left L5 and L6 spinal nerves. All animals developed neuropathic pain behaviors within 7 days after the surgery. For systemic delivery, three groups of rats were injected intraperitoneally with NMA (15 mg/kg), AHC (12.5 mg/kg), or saline. For peripheral routes of injection, rats were divided into 3 x 3 groups and injected with 100, 330, and 1000 nmol/kg doses of each NMA, AHC and 0.9% normal saline. NMA and AHC suppressed mechanical allodynia following peripheral administration but not following intraperitoneal injection. NMA was less potent but showed a longer-acting response than AHC. This study shows that NMA can be used to relieve mechanical allodynia and is a longer-acting agent than AHC. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Sung, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Res Grp,Dept Anesthesia & Crit Care, CN 149 3326,13th St, Charlestown, MA 02129 USA. EM bsung@partners.org NR 17 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 4 PY 2004 VL 357 IS 2 BP 115 EP 118 DI 10.1016/j.neulet.2003.12.048 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 780KZ UT WOS:000189381000010 PM 15036588 ER PT J AU Solomon, KR Sharma, P Chan, M Morrison, PT Finberg, RW AF Solomon, KR Sharma, P Chan, M Morrison, PT Finberg, RW TI CD109 represents a novel branch of the alpha 2-macroglobulin/complement gene family SO GENE LA English DT Article DE motifs; PCR cloning; CD109; macroglobulin; complement; phylogenic; thioester ID HUMAN T-CELLS; CONTAINING PROTEINS; HUMAN PLATELETS; SEQUENCE; IDENTIFICATION; COMPONENT; RECEPTOR; C3; FRAGMENTATION; EXPRESSION AB We report here the genomic organization and phylogenic relationships of CD109, a member of the the alpha2-macroglobulin/complement (AMCOM) gene family. CD109 is a GPI-linked glycoprotein expressed on endothelial cells, platelets, activated T-cells, and a wide variety of tumors. We cloned full-length CD109 cDNA from the mammalian U373 cell line by RT-PCR and performed analysis of its corresponding genomic sequence. The CD109 cDNA spans 128 kb of chromosome 6q with its 33 exons constituting approximately 3.3% of the total CD 109 genomic sequence. Sequence analysis revealed that CD 109 contains specific motifs in its N-terminus, that are highly conserved in all AMCOM members. CD109 also shares motifs with certain other AMCOM members including: (1) a thioester 'GCGEQ" motif, (2) a furin site of four positively charged amino acids, and (3) a double tyrosine near the C-terminus. Based on a phylogenic analysis of human CD 109 with other human homologs as well as orthologs from other mammalian species, C. elegans (ZK337.1) and E. coli homologs, we propose CD109 represents a novel and independent branch of the alpha2-macroglobulin/complement gene family (AMCOM) and may be its oldest member. (C) 2004 Elsevier B.V All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. RP Finberg, RW (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. EM Robert.Finberg@umassmed.edu FU NIGMS NIH HHS [R01 GM63244] NR 36 TC 17 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 3 PY 2004 VL 327 IS 2 BP 171 EP 183 DI 10.1016/j.gene.2003.11.025 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 803XI UT WOS:000220263400004 PM 14980714 ER PT J AU Bruce, ML Ten Have, TR Reynolds, CF Katz, II Schulberg, HC Mulsant, BH Brown, GK McAvay, GJ Pearson, JL Alexopoulos, GS AF Bruce, ML Ten Have, TR Reynolds, CF Katz, II Schulberg, HC Mulsant, BH Brown, GK McAvay, GJ Pearson, JL Alexopoulos, GS TI Reducing suicidal ideation and depressive symptoms in depressed older primary care patients - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LATE-LIFE DEPRESSION; LOGISTIC-REGRESSION MODELS; IMPROVING PRIMARY-CARE; BINARY RESPONSE DATA; MAJOR DEPRESSION; GERIATRIC DEPRESSION; CONSENSUS STATEMENT; QUALITY IMPROVEMENT; MINOR DEPRESSION; TERM TREATMENT AB Context Suicide rates are highest in late life; the majority of older adults who die by suicide have seen a primary care physician in preceding months. Depression is the strongest risk factor for late-life suicide and for suicide's precursor, suicidal ideation. Objective To determine the effect of a primary care intervention on suicidal ideation and depression in older patients. Design and Setting Randomized controlled trial known as PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) with patient recruitment from 20 primary care practices in New York City, Philadelphia, and Pittsburgh regions, May 1999 through August 2001. Participants Two-stage, age-stratified (60-74, greater than or equal to75 years) depression screening of randomly sampled patients; enrollment included patients who screened positive and a random sample of screened negative patients. This analysis included patients with a depression diagnosis (N=598). Intervention Treatment guidelines tailored for the elderly with care management compared with usual care. Main Outcome Measures Assessment of suicidal ideation and depression severity at baseline, 4 months, 8 months, and 12 months. Results Rates of suicidal ideation declined faster (P=.01) in intervention patients compared with usual care patients; at 4 months, in the intervention group, raw rates of suicidal ideation declined 12.9% points (29.4% to 16.5%) compared with 3.0% points (20.1% to 17.1% in usual care [P=.01]). Among patients reporting suicidal ideation, resolution of ideation was faster among intervention patients (P=.03); differences peaked at 8 months (70.7% vs 43.9% resolution; P=.005). Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction; group difference peaked at 4 months. The effects on depression were not significant among,, patients with minor depression unless suicidal ideation was present. Conclusions Evidence of the intervention's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination. The intervention's effectiveness in reducing suicidal ideation, regardless of depression severity, reinforces its role as a prevention strategy to reduce risk factors for suicide in late life. C1 Univ Pittsburgh, Dept Psychiat, WPIC, Sch Med, Pittsburgh, PA 15213 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, White Plains, NY USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. NIMH, Div Intervent & Serv Res, Bethesda, MD 20892 USA. RP Reynolds, CF (reprint author), Univ Pittsburgh, Dept Psychiat, WPIC, Sch Med, Room 1135-E,3811 Ohara St, Pittsburgh, PA 15213 USA. EM ReynoldsCF@msx.upmc.edu FU NIMH NIH HHS [K02 MH01634, K01 MH01613, P30 MH52129, P30 MH52247, P30 MH68638, R01 MH59366, R01 MH59380, R01 MH59381] NR 76 TC 553 Z9 560 U1 5 U2 38 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 2004 VL 291 IS 9 BP 1081 EP 1091 DI 10.1001/jama.291.9.1081 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 780AQ UT WOS:000189348900025 PM 14996777 ER PT J AU Crowley, WF Sherwood, L Salber, P Scheinberg, D Slavkin, H Tilson, H Reece, EA Catanese, V Johnson, SB Dobs, A Genel, M Korn, A Reame, N Bonow, R Grebb, J Rimoin, D AF Crowley, WF Sherwood, L Salber, P Scheinberg, D Slavkin, H Tilson, H Reece, EA Catanese, V Johnson, SB Dobs, A Genel, M Korn, A Reame, N Bonow, R Grebb, J Rimoin, D TI Clinical research in the United States at a crossroads - Proposal for a novel public-private partnership to establish a National Clinical Research Enterprise SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHALLENGES; QUALITY; SCIENCE AB The clinical research infrastructure of the United States is currently at a critical crossroads. To leverage the enormous biomedical research gains made in the past century efficiently, a drastic need exists to reengineer this system into a coordinated, safe, and more efficient and effective enterprise. To accomplish this task, clinical research must be transformed from its current state as a cottage industry to an enterprise-wide health care pipeline whose function is to bring the novel research from both government and private entities to the US public. We propose the establishment of a unique public-private partnership termed the National Clinical Research Enterprise (NCRE). Its agenda should consist of informed public participation, supportive information technologies, a skilled workforce, and adequate funding in clinical research. Devoting only 0.25% of the budgets from all health care stakeholders to support the NCRE would permit adequate funding to build the infrastructure required to address these problems in an enterprise fashion. All participants in the US health care delivery system must come together to focus on system-wide improvements that will benefit the public. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Ltd Liabil Corp, Med & Sci Associates, Lower Gwynedd, PA USA. Blue Shield Calif, San Francisco, CA USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. Columbia Univ, New York, NY USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Univ Arkansas, Coll Med, Little Rock, AR 72205 USA. Johns Hopkins Univ, Baltimore, MD USA. Yale Univ, Sch Med, Woodbridge, CT USA. Blue Cross Blue Shield Assoc, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Janssen Res Fdn, Titusville, NJ USA. RP Crowley, WF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM crowley.william@mgh.harvard.edu NR 25 TC 76 Z9 79 U1 8 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 2004 VL 291 IS 9 BP 1120 EP 1126 DI 10.1001/jama.291.9.1120 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 780AQ UT WOS:000189348900030 PM 14996782 ER PT J AU Spires, TL Grote, HE Varshney, NK Cordery, PM van Dellen, A Blakemore, C Hannan, AJ AF Spires, TL Grote, HE Varshney, NK Cordery, PM van Dellen, A Blakemore, C Hannan, AJ TI Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; environmental enrichment; BDNF; DARPP-32; transgenic mouse model; R6/1; NGF ID NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR BDNF; IMMUNOCYTOCHEMICAL LOCALIZATION; TRANSGENIC MICE; GENE-EXPRESSION; MESSENGER-RNA; BRAIN; DARPP-32; NEURONS; DOPAMINE AB Huntington's disease (HD) is a devastating neurodegenerative disorder caused by a CAG repeat expansion encoding an extended polyglutamine tract in the huntingtin protein. Transgenic mice expressing a human huntingtin transgene containing an expanded CAG repeat (R6/1 model) develop a neurodegenerative disorder closely resembling human HD. Previous work demonstrated that environmental enrichment delays the onset of motor symptoms in this mouse model. We confirmed that at 5 months of age, enrichment ameliorates motor symptoms ( assessed using the rotarod test) and prevents loss of body weight induced by the HD transgene. We further examined molecular consequences of enrichment by determining changes in protein levels in the neostriatum, hippocampus, and anterior cortex using quantitative Western blot analysis. Non-enriched HD mice have severe reductions in BDNF in the hippocampus and striatum at 5 months, which are entirely rescued by enrichment. BDNF levels are unaltered by HD in the anterior cortex, suggesting that enrichment might prevent HD-induced impairment of anterograde transport of this neurotrophin to the striatum. NGF is unaffected by HD. Non-enriched HD mice also exhibit deficits in dopamine and cAMP-regulated phosphoprotein ( 32 kDa) in striatum and anterior cortex. Environmental enrichment rescues the cortical but not the striatal deficit at 5 months. These results suggest that environmental enrichment benefits animals at early stages of the disease by rescuing protein deficits, possibly through rescuing transcription or protein transport problems. C1 Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. RP Spires, TL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St, Charlestown, MA 02129 USA. EM tara.spires@physiol.ox.ac.uik NR 54 TC 212 Z9 215 U1 2 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 MAR 3 PY 2004 VL 24 IS 9 BP 2270 EP 2276 DI 10.1523/JNEUROSCI.1658-03.2004 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 780PX UT WOS:000189391500020 PM 14999077 ER PT J AU Messas, E Bel, S Morichetti, MC Carrion, C Handschumacher, M Vilquin, JT Desnos, M Bruneval, P Menasche, P Carpentier, A Levine, RA Hagege, AA AF Messas, E Bel, S Morichetti, MC Carrion, C Handschumacher, M Vilquin, JT Desnos, M Bruneval, P Menasche, P Carpentier, A Levine, RA Hagege, AA TI Can autologous myoblast transplantation decrease chronic ischemic mitral regurgitation? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 INSERM, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 14A EP 14A DI 10.1016/S0735-1097(04)90055-1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500057 ER PT J AU Holmes, DR Fox, RD Tommaso, C Hodgson, PK Green, R Rocha-Singh, K Rosenfield, K AF Holmes, DR Fox, RD Tommaso, C Hodgson, PK Green, R Rocha-Singh, K Rosenfield, K TI The foundation for advanced medical education renal and iliac artery stent training program SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 32A EP 32A DI 10.1016/S0735-1097(04)90132-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500134 ER PT J AU MacNeill, BD Jang, IK Bouma, BE Iftimia, N Takano, M Yabushita, H Shishkov, M Tearney, GJ AF MacNeill, BD Jang, IK Bouma, BE Iftimia, N Takano, M Yabushita, H Shishkov, M Tearney, GJ TI In vivo macrophage Imaging of acute coronary syndromes with intracoronary optical coherence tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 33A EP 33A DI 10.1016/S0735-1097(04)90139-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500141 ER PT J AU Reddy, VY Malchano, Z Neuzil, P Weichet, J Ruskin, JN AF Reddy, VY Malchano, Z Neuzil, P Weichet, J Ruskin, JN TI Registration of cardiac computed tomography images with three-dimensional electroanatomical mapping to guide catheter manipulation in the left atrium: Implications for pulmonary venous isolation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 115A EP 116A DI 10.1016/S0735-1097(04)90482-2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500484 ER PT J AU Whang, W Albert, CM Lampert, R Sears, SF Conti, JB Wang, PJ Ruskin, JN Muller, JE Mittleman, MA AF Whang, W Albert, CM Lampert, R Sears, SF Conti, JB Wang, PJ Ruskin, JN Muller, JE Mittleman, MA TI A multicenter study of depression as a predictor for appropriate shocks among patients with implantable cardioverter delibrillators SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 116A EP 116A DI 10.1016/S0735-1097(04)90485-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500487 ER PT J AU Reddy, VY Malchano, ZJ Holmvang, G Schmidt, EJ Houghtaling, C Chan, RC Ruskin, JN AF Reddy, VY Malchano, ZJ Holmvang, G Schmidt, EJ Houghtaling, C Chan, RC Ruskin, JN TI Registration of cardiac magnetic resonance images with three-dimensional electroanatomical mapping to guide catheter ablation in the left ventricle SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 130A EP 130A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500549 ER PT J AU Hu, JC Machuca, K DePeralta, S Singh, B Feliciano, Z AF Hu, JC Machuca, K DePeralta, S Singh, B Feliciano, Z TI Ibutilide improves cardioversion success rates in patients on chronic amiodarone therapy with persistent atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 136A EP 136A DI 10.1016/S0735-1097(04)90573-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500575 ER PT J AU Wood, MJ Yoerger, DM Scherrer-Crosbie, M Derumeaux, GA Douglas, PS Marshall, JE Weyman, AE Picard, MH AF Wood, MJ Yoerger, DM Scherrer-Crosbie, M Derumeaux, GA Douglas, PS Marshall, JE Weyman, AE Picard, MH TI Impaired right ventricular systolic function following completion of prolonged strenuous exertion SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 168A EP 168A DI 10.1016/S0735-1097(04)90713-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500715 ER PT J AU Tung, RH Garcia, C Pino, R Morss, AM Lewandrowski, K Lewandrowski, E Thompson, BT Fifer, MA Januzzi, JL AF Tung, RH Garcia, C Pino, R Morss, AM Lewandrowski, K Lewandrowski, E Thompson, BT Fifer, MA Januzzi, JL TI B-tpe natriuretic peptide strongly predicts mortality in intensive care unit shock SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 169A EP 170A DI 10.1016/S0735-1097(04)90720-6 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500722 ER PT J AU Rumsfeld, JS Jones, P Whooley, MA Sullivan, MD Pitt, B Weintraub, WS Spertus, JA AF Rumsfeld, JS Jones, P Whooley, MA Sullivan, MD Pitt, B Weintraub, WS Spertus, JA TI Depression predicts mortality and hospitalization in patients with acute myocardial infarction complicated by heart failure: Data from the EPHESUS trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Denver VA Med Ctr, Denver, CO USA. Univ Missouri, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 179A EP 180A DI 10.1016/S0735-1097(04)90765-6 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500767 ER PT J AU Dougherty, R Rohrer, JL Hayden, D Leder, BZ AF Dougherty, R Rohrer, JL Hayden, D Leder, BZ TI Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly hypogonadal men: A double-blind placebo-controlled randomized trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 182A EP 182A DI 10.1016/S0735-1097(04)90775-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500777 ER PT J AU Staszewsky, L Wong, ML Barlera, S Carretta, E Masson, S Latini, R Maggioni, AR Cohn, JN Tognoni, G AF Staszewsky, L Wong, ML Barlera, S Carretta, E Masson, S Latini, R Maggioni, AR Cohn, JN Tognoni, G TI Comparative yield of clinical, laboratory, echocardiographic, and neurohormonal predictors of outcome in heart failure patients (Val-HeFT data) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Ist Ric Farmacol, Milan, Italy. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 199A EP 199A DI 10.1016/S0735-1097(04)90845-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500847 ER PT J AU Morgan, JG Wood, MJ Weyman, AE AF Morgan, JG Wood, MJ Weyman, AE TI Mitral and tricuspid inflow velocities and their variation with respiration are better predictors of cardiac tamponade than right atrial and ventricular collapse: A combined echocardiographic and hemodynamic study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 203A EP 203A DI 10.1016/S0735-1097(04)90863-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500865 ER PT J AU Tajjaj, JA Mirza, S Rayburn, BK Pinderski, LJ Benza, RL Foley, BA Pamboukian, S Bourge, RC AF Tajjaj, JA Mirza, S Rayburn, BK Pinderski, LJ Benza, RL Foley, BA Pamboukian, S Bourge, RC TI Outcomes of peripartum cardiomyopathy in the current era of heart failure management SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Univ Alabama, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 205A EP 205A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500874 ER PT J AU Nesta, F Yoerger, DM Picard, MH Fifer, MA Palacios, IF Vlahakes, GJ Levine, RA Hung, J AF Nesta, F Yoerger, DM Picard, MH Fifer, MA Palacios, IF Vlahakes, GJ Levine, RA Hung, J TI Mechanism of systolic anterior motion and regurgitation, post septal ablation in hypertrophic cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 215A EP 215A DI 10.1016/S0735-1097(04)90913-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500915 ER PT J AU Weinrauch, LA D'Elia, JA Gleason, RE Burger, A Lee, A AF Weinrauch, LA D'Elia, JA Gleason, RE Burger, A Lee, A TI Left ventricular mass reduction in type 1 diabetes mellitus SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 221A EP 221A DI 10.1016/S0735-1097(04)90939-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500941 ER PT J AU Januzzi, JL Camargo, CA Anwaruddin, S Baggish, A Chen, A Krauser, D Tung, R Nagumey, T Chae, C Lloyd-Jones, DM Brown, DF Sluss, PM Lewandrowski, EL Lewandrowski, KB AF Januzzi, JL Camargo, CA Anwaruddin, S Baggish, A Chen, A Krauser, D Tung, R Nagumey, T Chae, C Lloyd-Jones, DM Brown, DF Sluss, PM Lewandrowski, EL Lewandrowski, KB TI Pro B-natriuretic peptide (BNP) measurement for the emergency diagnosis of congestive heart failure: The ProBNP Investigation of Dyspnea in the Emergency Department study (PRIDE) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 235A EP 235A DI 10.1016/S0735-1097(04)91000-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501002 ER PT J AU Dumaine, R Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Wiviott, SD Cannon, CP Antman, EM Braunwald, E AF Dumaine, R Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Wiviott, SD Cannon, CP Antman, EM Braunwald, E CA TIMI Study Grp TI Association of glomerular filtration rate on presentation with subsequent mortality in non-ST elevation acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 250A EP 250A DI 10.1016/S0735-1097(04)91062-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501064 ER PT J AU Anwaruddin, S Januzzi, JL Lewandrowski, KB Lewandrowski, E AF Anwaruddin, S Januzzi, JL Lewandrowski, KB Lewandrowski, E TI Ischemia modified albumin improves the sensitivity and negative predictive value of standard cardiac biomarkers for the diagnosis of myocardial ischemia SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 258A EP 258A DI 10.1016/S0735-1097(04)91096-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501098 ER PT J AU Gelfand, EV Morrow, DA Sabatine, MS Rifai, N Murphy, S McCabe, C Antman, EM AF Gelfand, EV Morrow, DA Sabatine, MS Rifai, N Murphy, S McCabe, C Antman, EM CA TIMI Study Grp TI Risk stratification in ST-segment elevation myocardial infarction with multiple biomarkers SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, TIMI Study Grp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 259A EP 259A DI 10.1016/S0735-1097(04)91102-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501104 ER PT J AU Karmpaliotis, D Kirtane, AJ Murphy, SA Kosmidou, I Budiu, D Guerra, D Giugliano, R Cannon, CP Antman, EM Braunwald, E Gibson, CM AF Karmpaliotis, D Kirtane, AJ Murphy, SA Kosmidou, I Budiu, D Guerra, D Giugliano, R Cannon, CP Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI Calcification of the culprit lesion is associated with adverse clinical outcomes in ST elevation myocardial infarction patients treated with fibrinolytic therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 261A EP 262A DI 10.1016/S0735-1097(04)91112-6 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501114 ER PT J AU Kirtane, AJ Karmpaliotis, D Weisbord, A Bui, A Murphy, SA Budiu, D Kosmidou, I Aroesty, JM Giugliano, RP Cannon, CP Antman, EM Braunwald, E Gibson, CM AF Kirtane, AJ Karmpaliotis, D Weisbord, A Bui, A Murphy, SA Budiu, D Kosmidou, I Aroesty, JM Giugliano, RP Cannon, CP Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI Angiographically apparent thrombus after fibrinolytic administration is associated with impaired epicardial flow and myocardial perfusion in ST elevation myocardial infarction patients with open arteries SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 262A EP 262A DI 10.1016/S0735-1097(04)91114-X PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501116 ER PT J AU Deans, KJ Minneci, PC Banks, SM Solomon, MA MacGillivray, TE Hoffman, WD Natanson, C Vlahakes, GJ AF Deans, KJ Minneci, PC Banks, SM Solomon, MA MacGillivray, TE Hoffman, WD Natanson, C Vlahakes, GJ TI Coronary artery bypass grafting without cardiopulmonary bypass increases survival rate and decreases morbidity: A meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 268A EP 268A DI 10.1016/S0735-1097(04)91139-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501141 ER PT J AU Sabatine, MS Morrow, DA Giugliano, RP Murphy, SA McCabe, CH Gibson, CM Cannon, CP Antman, EM Braunwald, E AF Sabatine, MS Morrow, DA Giugliano, RP Murphy, SA McCabe, CH Gibson, CM Cannon, CP Antman, EM Braunwald, E CA TIMI Study Grp TI Low hemoglobin predicts worse clinical outcomes in acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 278A EP 278A DI 10.1016/S0735-1097(04)91180-1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501182 ER PT J AU Martinezclark, P Karmpaliotis, D Murphy, SA Wiviott, SD Bigelow, B Kosmidou, I Chang, A Cannon, CP Giugliano, RP Gibson, CM AF Martinezclark, P Karmpaliotis, D Murphy, SA Wiviott, SD Bigelow, B Kosmidou, I Chang, A Cannon, CP Giugliano, RP Gibson, CM TI The association of race with angiographic and clinical outcomes following fibrinolytic administration SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. TIMI Data Coordinating Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 305A EP 305A DI 10.1016/S0735-1097(04)91289-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501291 ER PT J AU Walsh, MC Bourcier, T Takahashi, K Shi, L Ezekowitz, A Stahl, GL AF Walsh, MC Bourcier, T Takahashi, K Shi, L Ezekowitz, A Stahl, GL TI Myocardial ischemia-reperfusion injury is dependent on lectin complement activation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 305A EP 305A DI 10.1016/S0735-1097(04)91291-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501293 ER PT J AU Mega, JL Sabatine, MS Morrow, DA de Lemos, JA Murphy, SA McCabe, CH Cannon, CP Braunwald, E AF Mega, JL Sabatine, MS Morrow, DA de Lemos, JA Murphy, SA McCabe, CH Cannon, CP Braunwald, E CA TIMI Study Grp TI Higher levels of thrombus precursor protein are associated with increased death and ischemic complications in patients with acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 306A EP 307A DI 10.1016/S0735-1097(04)91296-X PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501298 ER PT J AU Achenbach, S Moselewski, F Ropers, D Pohle, K Hoffman, U Ferencik, M Abbara, S Cury, R Chan, R Jang, IK Brady, T Daniel, WG AF Achenbach, S Moselewski, F Ropers, D Pohle, K Hoffman, U Ferencik, M Abbara, S Cury, R Chan, R Jang, IK Brady, T Daniel, WG TI Assessment of coronary atherosclerotic plaque composition by multidetector computed tomography: Comparison to intravascular ultrasound SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 312A EP 313A DI 10.1016/S0735-1097(04)91322-8 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501324 ER PT J AU Uemura, T Otsuji, Y Kumanohoso, T Yuge, K Nakashiki, K Yuasa, T Kisanuki, A Minagoe, S Levine, RA Tei, C AF Uemura, T Otsuji, Y Kumanohoso, T Yuge, K Nakashiki, K Yuasa, T Kisanuki, A Minagoe, S Levine, RA Tei, C TI Ischemic mitral regurgitation is independent of papillary muscle dysfunction: Insights from tissue Doppler strain imaging in patients with inferior myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Kagoshima Univ, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 333A EP 333A DI 10.1016/S0735-1097(04)91410-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501412 ER PT J AU Yosefy, C Levine, RA Hung, J AF Yosefy, C Levine, RA Hung, J TI Proximal flow convergence region as assessed by real-time 3-D echocardiography: Challenging the hemispheric assumption SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 355A EP 356A DI 10.1016/S0735-1097(04)91503-3 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501505 ER PT J AU Weyman, AE Gardin, J Davidoff, R Ryan, T Weissman, N AF Weyman, AE Gardin, J Davidoff, R Ryan, T Weissman, N TI Effects of body size, stroke volume, age, and gender on left atrial dimension SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 358A EP 358A DI 10.1016/S0735-1097(04)91513-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501515 ER PT J AU Witzke, CF Holmvang, G Lewis, GD Afridi, N Semigran, MJ Dec, GW Palacios, IF AF Witzke, CF Holmvang, G Lewis, GD Afridi, N Semigran, MJ Dec, GW Palacios, IF TI Gadolinium-enhanced magnetic resonance imaging in patients with left ventricular apical ballooning syndrome identifies acute myocarditis as a potential etiology of this syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 366A EP 366A DI 10.1016/S0735-1097(04)91549-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501551 ER PT J AU Morgan, JG Derumeaux, G Ichinose, F Lee, C Hataishi, R Bloch, KD Picard, MH Scherrer-Crosbie, M AF Morgan, JG Derumeaux, G Ichinose, F Lee, C Hataishi, R Bloch, KD Picard, MH Scherrer-Crosbie, M TI Age-related left ventricular function alterations in mice: A tissue Doppler imaging study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rouen, Rouen, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 373A EP 373A DI 10.1016/S0735-1097(04)91579-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501581 ER PT J AU Thorndike, A Rigotti, N Regan, S McKool, K Swartz, S Singer, D Pasternak, R AF Thorndike, A Rigotti, N Regan, S McKool, K Swartz, S Singer, D Pasternak, R TI Depression in smokers hospitalized with acute cardiovascular disease increases nicotine withdrawal symptoms and early relapse to smoking SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Portland, ME 04102 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 417A EP 417A DI 10.1016/S0735-1097(04)91761-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501764 ER PT J AU Vaturi, M Hung, J Levine, RA AF Vaturi, M Hung, J Levine, RA TI Increased tricuspid regurgitation in patients with pulmonary hypertension when left ventricular dysfunction is present: A new mechanism of malcoaptation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 440A EP 441A DI 10.1016/S0735-1097(04)91858-X PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501861 ER PT J AU Uemura, T Otsuji, Y Kumanohoso, T Takasaki, K Yuasa, T Nakashiki, K Yu, B Kisanuki, A Minagoe, S Levine, RA Tei, C AF Uemura, T Otsuji, Y Kumanohoso, T Takasaki, K Yuasa, T Nakashiki, K Yu, B Kisanuki, A Minagoe, S Levine, RA Tei, C TI Comparison of left ventricular sphericity and papillary muscle tethering in the mechanism of ischemic mitral regurgitation in patients with inferior myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Kagoshima Univ, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 441A EP 441A DI 10.1016/S0735-1097(04)91860-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501863 ER PT J AU Grazette, L Boecker, W Semigran, M Force, T Hajjar, RJ Rosenzweig, A AF Grazette, L Boecker, W Semigran, M Force, T Hajjar, RJ Rosenzweig, A TI Anti-ErbB2 modulation of Bcl-x(L)/Bcl-x(S) causes mitochondrial dysfunction and apoptosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 455A EP 455A DI 10.1016/S0735-1097(04)91922-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501925 ER PT J AU Goldfine, A Beckman, J Devlin, H Hurley, S Creager, M AF Goldfine, A Beckman, J Devlin, H Hurley, S Creager, M TI The role of a family history of diabetes on endothelial function SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 468A EP 468A DI 10.1016/S0735-1097(04)91983-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501986 ER PT J AU Ebrahimi, R Wolf, C Saleh, J AF Ebrahimi, R Wolf, C Saleh, J TI Beneficial effect of oral acetylcysteine for prevention of contrast-induced nephropathy in patients with renal insufficiency: A meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 W Los Angeles VA, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 509A EP 510A DI 10.1016/S0735-1097(04)92158-4 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388502161 ER PT J AU Tawakol, A Migrino, RQ Gewirtz, H Muller, JE Brady, T Fischman, AJ AF Tawakol, A Migrino, RQ Gewirtz, H Muller, JE Brady, T Fischman, AJ TI Noninvasive characterization of carotid plaque inflammation in humans with FDG-positron emission tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 516A EP 516A DI 10.1016/S0735-1097(04)92186-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388502189 ER PT J AU Achenbach, S AF Achenbach, S TI Editorial comment - Detection of coronary stenoses by multidetector computed tomography: It's all about resolution SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID MAGNETIC-RESONANCE ANGIOGRAPHY; ARTERY STENOSES; SYNCHROTRON-RADIATION C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM Sachenbach@Partners.org NR 20 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 BP 840 EP 841 DI 10.1016/j.jacc.2003.12.014 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779AP UT WOS:000189273700021 PM 14998626 ER PT J AU Achenbach, S Ropers, D Hofmann, U MacNeill, B Baum, U Pohle, K Brady, TJ Pomerantsev, E Ludwig, J Flachskampf, FA Wicky, S Jang, IK Daniel, WG AF Achenbach, S Ropers, D Hofmann, U MacNeill, B Baum, U Pohle, K Brady, TJ Pomerantsev, E Ludwig, J Flachskampf, FA Wicky, S Jang, IK Daniel, WG TI Assessment of coronary remodeling in stenotic and nonstenotic coronary atherosclerotic lesions by multidetector spiral computed tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID INADEQUATE COMPENSATORY ENLARGEMENT; INTRAVASCULAR ULTRASOUND; IN-VIVO; ARTERY DISEASE; PLAQUE VULNERABILITY; VESSEL; ANGIOGRAPHY; STENOSES; ANGINA AB OBJECTIVES This study was designed to investigate whether contrast-enhanced multidetector spiral CT (MDCT) permits assessment of remodeling in coronary atherosclerotic lesions. BACKGROUND With sufficient image quality, MDCT permits noninvasive visualization of the coronary arteries, but its ability to assess remodeling has not been evaluated. METHODS Out of 102 patients in whom MDCT (16-slice scanner, intravenous contrast, 0.75-mm collimation, 420 ms rotation) was performed before invasive coronary angiography, 44 patients with high-quality MDCT data sets showing atherosclerotic plaque in a proximal coronary artery segment were chosen for evaluation. In multiplanar reconstructions orthogonal to the coronary artery, the cross-sectional vessel area was measured for the respective lesion and for a reference segment proximal to the lesion. The "Remodeling Index" was calculated by dividing the vessel area in the lesion by the reference segment. Results were correlated to the presence of stenosis (>500% diameter reduction) in invasive angiography. In a subset of 13 patients, MDCT measurements were verified by IVUS. RESULTS Reference vessel area was not significantly different between nonstenotic versus stenotic lesions (20 +/- 8 mm(2), n = 23 vs. 22 +/- 8 mm(2), n = 21). The mean Remodeling Index was significantly higher in nonstenotic than in stenotic lesions (1.3 +/- 0.2 vs. 1.0 +/- 0.2, p < 0.001). In five stenotic lesions, "negative remodeling" (Remodeling Index less than or equal to0.95) was observed. Cross-sectional vessel areas and Remodeling Indices measured by MDCT correlated closely to IVUS (r(2) = 0.77 and r(2) = 0.82, respectively). CONCLUSIONS Multidetector spiral CT may permit assessment of remodeling of coronary atherosclerotic lesions in selected data sets of sufficient quality. (C) 2004 by the American College of Cardiology Foundation. C1 Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Diagnost Radiol, Erlangen, Germany. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Achenbach, S (reprint author), Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, Ulmenweg 18, D-91054 Erlangen, Germany. EM Stephan.achenbach@med2.med.uni-erlangen.de NR 23 TC 216 Z9 230 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 BP 842 EP 847 DI 10.1016/j.jacc.2003.09.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779AP UT WOS:000189273700022 PM 14998627 ER PT J AU Huang, CC Venturi, M Majeed, S Moore, MJ Phogat, S Zhang, MY Dimitrov, DS Hendrickson, WA Robinson, J Sodroski, J Wyatt, R Choe, H Farzan, M Kwong, PD AF Huang, CC Venturi, M Majeed, S Moore, MJ Phogat, S Zhang, MY Dimitrov, DS Hendrickson, WA Robinson, J Sodroski, J Wyatt, R Choe, H Farzan, M Kwong, PD TI Structural basis of tyrosine sulfation and V-H-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; CHEMOKINE RECEPTORS; CCR5; EPITOPES; ENTRY; RETROVIRUS; AIDS; SPECIFICITY AB The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the HIV-1 coreceptor is protected from humoral recognition by multiple layers of camouflage. Here we present sequence and genomic analyses for 12 antibodies that pierce these defenses and determine the crystal structures of 5. The data reveal mechanisms and atomic-level details for three unusual immune features: posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an alternative molecular mechanism controlling such sulfation, and highly selective V-H-gene usage. When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Dept Med Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. NCI, NIH, Frederick, MD 21702 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA. EM pdkwong@nih.gov FU NIAID NIH HHS [R01 AI043891] NR 39 TC 166 Z9 173 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 MAR 2 PY 2004 VL 101 IS 9 BP 2706 EP 2711 DI 10.1073/pnas.0308527100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300014 PM 14981267 ER PT J AU Yang, W Shimaoka, M Salas, A Takagi, J Springer, TA AF Yang, W Shimaoka, M Salas, A Takagi, J Springer, TA TI Intersubunit signal transmission in integrins by a receptor-like interaction with a pull spring SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; I-LIKE DOMAIN; CRYSTAL-STRUCTURE; LIGAND-BINDING; A-DOMAIN; CONFORMATIONAL-CHANGES; EXTRACELLULAR SEGMENT; STRUCTURAL BASIS; DISULFIDE BONDS; ALPHA-SUBUNITS AB The function of some multidomain proteins is regulated by interdomain communication. We use second-site suppressor cysteine mutations to test a hypothesis on how the inserted (I)-like domain in the integrin beta-subunit regulates ligand binding by the neighboring I domain in the integrin alpha- subunit [Huth, J. R., Olejniczak, E. T., Mendoza, R., Liang, H., Harris, E. A., et al. (2000) Proc. Natl. Acad Sci. USA 97, 5231-5236; and Alonso, J. L., Essafi, M., Xiong, J. P., Stehle, T. & Arnaout, M. A. (2002) Curr. Siol. 12, R340-R342]. The hypothesis is that an interaction between the beta I- like metal ion-dependent adhesion site (MIDAS) and an intrinsic ligand in the linker following the alpha I domain, Glu- 310, exerts a pull that activates the alpha I domain. Individual mutation of alpha(L) linker residue Glu-310 or beta(2) MIDAS residues Ala-210 or Tyr-115 to cysteine abolishes I domain activation, whereas the double mutation of alpha(L)-E310C with either beta2-A210C or beta2-Y115C forms a disulfide bond that constitutively activates ligand binding. The disulfide-bonded mutant is resistant to small molecule antagonists that bind to the beta I-like domain near its interface with the alpha I domain and inhibit communication between these domains but remains susceptible to small molecule antagonists that bind underneath the I domain alpha7-helix and certain allosteric antagonistic antibodies. Thus, the alpha7-helix and its linker are better modeled as a pull spring than a bell rope. The results suggest that alpha(L) residue Glu-310, which is universally conserved in all I domain-containing integrins, functions as an intrinsic ligand for the beta I-like domain, and that when integrins are activated, the beta I-like MIDAS binds to Glu-310, pulls the spring, and thereby activates the alpha I domain. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NCI NIH HHS [R37 CA031798, R01 CA031798, CA31798] NR 36 TC 70 Z9 75 U1 2 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 MAR 2 PY 2004 VL 101 IS 9 BP 2906 EP 2911 DI 10.1073/pnas.0307340101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300048 PM 14978279 ER PT J AU Teng, YD Choi, H Onario, RC Zhu, S Desilets, FC Lan, SM Woodard, EJ Snyder, EY Eichler, ME Friedlander, RM AF Teng, YD Choi, H Onario, RC Zhu, S Desilets, FC Lan, SM Woodard, EJ Snyder, EY Eichler, ME Friedlander, RM TI Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODEL; MICROGLIAL ACTIVATION; MOTOR-NEURONS; RAT; APOPTOSIS; CASPASE-1; DISEASE; BRAIN; MICE AB We investigated whether permeability transition-mediated release of mitochondrial cytochrome c is a potential therapeutic target for treating acute spinal cord injury (SCI). Based on previous reports, minocycline, a second-generation tetracycline, exerts neuroprotection partially by inhibiting mitochondrial cytochrome c release and reactive microgliosis. We first evaluated cytochrome c release at the injury epicenter after a T10 contusive SCI in rats. Cytochrome c release peaked at approximate to4-8 h postinjury. A dose-response study generated a safe pharmacological regimen that enabled i.p. minocycline to significantly lower cytosolic cytochrome c at the epicenter 4 h after SCI. In the long-term study, i.p. minocycline (90 mg/kg administered 1 h after SCI followed by 45 mg/kg administered every 12 h for 5 days) markedly enhanced long-term hind limb locomotion relative to that of controls. Coordinated motor function and hind limb reflex recoveries also were improved significantly. Histopathology suggested that minocycline treatment alleviated later-phase tissue loss, with significant sparing of white matter and ventral horn motoneurons at levels adjacent to the epicenter. Furthermore, glial fibrillary acidic protein and 2',3' cyclic nucleotide 3' phosphodiesterase immunocytochemistry showed an evident reduction in astrogliosis and enhanced survival of oligodendrocytes. Therefore, release of mitochondrial cytochrome c is an important secondary injury mechanism in SCI. Drugs with multifaceted effects in antagonizing this process and microgliosis may protect a proportion of spinal cord tissue that is clinically significant for functional recovery. Minocycline, with its proven clinical safety, capability to cross the blood-brain barrier, and demonstrated efficacy during a clinically relevant therapeutic window, may become an effective therapy for acute SCI. C1 Harvard Univ, Sch Med, Dept Neurosurg, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neuroapoptosis Lab, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Boston Healthcare Syst, SCI Lab, W Roxbury, MA 02132 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Teng, YD (reprint author), 300 Longwood Ave,314 Enders, Boston, MA 02115 USA. EM yang_teng@hms.harvard.edu RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 FU NINDS NIH HHS [R01 NS39324, 1-R21-NS41999, NS41635, R01 NS039324, R01 NS041635] NR 51 TC 206 Z9 215 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 MAR 2 PY 2004 VL 101 IS 9 BP 3071 EP 3076 DI 10.1073/pnas.0306239101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300076 PM 14981254 ER PT J AU Schubert, M Gautam, D Surjo, D Ueki, K Baudler, S Schubert, D Kondo, T Alber, J Galldiks, N Kustermann, E Arndt, S Jacobs, AH Krone, W Kahn, CR Bruning, JC AF Schubert, M Gautam, D Surjo, D Ueki, K Baudler, S Schubert, D Kondo, T Alber, J Galldiks, N Kustermann, E Arndt, S Jacobs, AH Krone, W Kahn, CR Bruning, JC TI Role for neuronal insulin resistance in neurodegenerative diseases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BRAIN GLUCOSE-METABOLISM; CENTRAL-NERVOUS-SYSTEM; BODY-WEIGHT; FOOD-INTAKE; TAU-PHOSPHORYLATION; ALZHEIMERS-DISEASE; TRANSGENIC MICE; RAT-BRAIN; GROWTH; RECEPTORS AB Impairment of insulin signaling in the brain has been linked to neurodegenerative diseases. To test the hypothesis that neuronal insulin resistance contributes to defects in neuronal function, we have performed a detailed analysis of brain/neuron-specific insulin receptor knockout (NIRKO) mice. We find that NIRKO mice exhibit a complete loss of insulin-mediated activation of phosphatidylinositol 3-kinase and inhibition of neuronal apoptosis. In intact animals, this loss results in markedly reduced phosphorylation of Akt and GSK3beta, leading to substantially increased phosphorylation of the microtubule-associated protein Tau, a hallmark of neurodegenerative diseases. Nevertheless, these animals exhibit no alteration in neuronal proliferation/survival, memory, or basal brain glucose metabolism. Thus, lack of insulin signaling in the brain may lead to changes in Akt and GSK3beta activity and Tau hyperphosphorylation but must interact with other mechanisms for development of Alzheimer's disease. C1 Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany. Univ Cologne, Inst Anat, D-50931 Cologne, Germany. Univ Cologne, Dept Neurol, D-50931 Cologne, Germany. Max Planck Inst Neurol Res, D-50931 Cologne, Germany. Univ Cologne, Klin 2, D-50924 Cologne, Germany. Univ Cologne, Poliklin Innere Med, D-50924 Cologne, Germany. Ctr Mol Med Cologne, D-50924 Cologne, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bruning, JC (reprint author), Univ Cologne, Inst Genet, Weyertal 121, D-50931 Cologne, Germany. EM jens.bruening@uni-koeln.de RI Schubert, Markus/F-5150-2010 FU NIDDK NIH HHS [R01 DK031036, R37 DK031036, DK 31036] NR 30 TC 309 Z9 329 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 MAR 2 PY 2004 VL 101 IS 9 BP 3100 EP 3105 DI 10.1073/pnas.0308724101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300081 PM 14981233 ER PT J AU Mohi, MG Boulton, C Gu, TL Sternberg, DW Neuberg, D Griffin, JD Gilliland, DG Neel, BG AF Mohi, MG Boulton, C Gu, TL Sternberg, DW Neuberg, D Griffin, JD Gilliland, DG Neel, BG TI Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; BCR-ABL; MAMMALIAN TARGET; PHILADELPHIA-CHROMOSOME; IMATINIB MESYLATE; IN-VITRO; 3-KINASE/AKT PATHWAY; HEMATOPOIETIC-CELLS; PROGENITOR CELLS AB Abnormal protein tyrosine kinases (PTKs) cause many human leukemias. For example, BCR/ABL causes chronic myelogenous leukemia (CML), whereas FLT3 mutations contribute to the pathogenesis of acute myelogenous leukemia. The ABL inhibitor Imatinib (Gleevec, STI571) has remarkable efficacy for treating chronic phase CML, and FLT3 inhibitors (e.g., PKC412) show similar promise in preclinical studies. However, resistance to PTK inhibitors is a major emerging problem that may limit long-term therapeutic efficacy. Development of rational combination therapies will probably be required to effect cures of these and other neoplastic disorders. Here, we report that the mTOR inhibitor rapamycin synergizes with Imatinib against BCR/ABL-transformed myeloid and lymphoid cells and increases survival in a murine CIVIL model. Rapamycin/Imatinib combinations also inhibit Imatinib-resistant mutants of BCR/ABL, and rapamycin plus PKC412 synergistically inhibits cells expressing PKC412-sensitive or resistant leukemogenic FLT3 mutants. Biochemical analyses raise the possibility that inhibition of 4E-BP1 phosphorylation may be particularly important for the synergistic effects of PTK inhibitor/rapamycin combinations. Addition of a mitogen-activated protein kinase kinase inhibitor to rapamycin or rapamycin plus PTK inhibitor further increases efficacy. Our results suggest that simultaneous targeting of more than one signaling pathway required by leukemogenic PTKs may improve the treatment of primary and relapsed CML and/or acute myelogenous leukemia caused by FLT3 mutations. Similar strategies may be useful for treating solid tumors associated with mutant and/or overexpressed PTKs. C1 Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Mohi, MG (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Canc Biol Program, New Res Bldg,330 Brookline Ave, Boston, MA 02215 USA. EM gmohi@bidmc.harvard.edu FU NCI NIH HHS [P01 CA066996, P01 CA66996]; NIDDK NIH HHS [R01 DK50654, P01 DK050654, P01 DK50693, R01 DK050693] NR 48 TC 181 Z9 193 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3130 EP 3135 DI 10.1073/pnas.0400063101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300086 PM 14976243 ER PT J AU Maxwell, MM Pasinelli, P Kazantsev, AG Brown, RH AF Maxwell, MM Pasinelli, P Kazantsev, AG Brown, RH TI RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; DOUBLE-STRANDED-RNA; MAMMALIAN-CELLS; GENE-EXPRESSION; MESSENGER-RNA; NEURAL CELLS; IN-VITRO; MUTATIONS; DISEASE; MICE AB Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disorder resulting from selective death of motor neurons in the brain and spinal cord. In approximate to25% of familial ALS cases, the disease is caused by dominantly acting point mutations in the gene encoding cytosolic Cu,Zn superoxide dismutase (SOD1). In cell culture and in rodent models of ALS, mutant SOD1 proteins exhibit dose-dependent toxicity; thus, agents that reduce mutant protein expression would be powerful therapeutic tools. A wealth of recent evidence has demonstrated that the mechanism of RNA-mediated interference (RNAi) can be exploited to achieve potent and specific gene silencing in vitro and in vivo. We have evaluated the utility of RNAi for selective silencing of mutant SOD1 expression in cultured cells and have identified small interfering RNAs capable of specifically inhibiting expression of ALS-linked mutant, but not wild-type, SOD1. We have investigated the functional effects of RNAi-mediated silencing of mutant SOD1 in cultured murine neuroblastoma cells. in this model, stable expression of mutant, but not wild-type, human SOD1 sensitizes cells to cytotoxic stimuli. We find that silencing of mutant SOD1 protects these cells against cyclosporin A-induced cell death. These results demonstrate a positive physiological effect caused by RNAi-mediated silencing of a dominant disease allele. The present study further supports the therapeutic potential of RNAi-based methods for the treatment of inherited human diseases, including ALS. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, High Throughput Screening Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Brown, RH (reprint author), 114 16th St,Room 3125, Charlestown, MA 02129 USA. EM rhbrown@partners.org FU NIA NIH HHS [5P01 AG12992-9, P01 AG012992, R03 AG 22152-01, R03 AG022152]; NINDS NIH HHS [5PO1 NS40828-02, P01 NS040828] NR 37 TC 40 Z9 47 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 MAR 2 PY 2004 VL 101 IS 9 BP 3178 EP 3183 DI 10.1073/pnas.0308726100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300094 PM 14981234 ER PT J AU Grunwald, ME Mellem, JE Strutz, N Maricq, AV Kaplan, JM AF Grunwald, ME Mellem, JE Strutz, N Maricq, AV Kaplan, JM TI Clathrin-mediated endocytosis is required for compensatory regulation of GLR-1 glutamate receptors after activity blockade SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INORGANIC-PHOSPHATE TRANSPORTER; LONG-TERM DEPRESSION; AMPA RECEPTORS; CAENORHABDITIS-ELEGANS; C-ELEGANS; SYNAPTIC-TRANSMISSION; UBIQUITIN; INTERNALIZATION; PLASTICITY; NEURONS AB Chronic changes in neural activity trigger a variety of compensatory homeostatic mechanisms by which neurons maintain a normal level of synaptic input. Here we show that chronic activity blockade triggers a compensatory change in the abundance of GLR-1, a Caenorhabditis elegans glutamate receptor. In mutants lacking a voltage-dependent calcium channel (unc-2) or a vesicular glutamate transporter (VGLUT; eat-4), the abundance of GLR-1 in the ventral nerve cord was increased. Similarly, the amplitude of glutamate-evoked currents in ventral cord interneurons was increased in eat-4 VGLUT mutants compared with wild-type controls. The effects of eat-4 VGLUT mutations on GLR-1 abundance in the ventral cord were eliminated in double mutants lacking both the clathrin adaptin protein unc-11 AP180 and eat-4 VGLUT. In contrast, mutations that decreased ubiquitination of GLR-1 did not prevent increased ventral cord abundance of GLR-1 in eat-4 VGLUT mutants. Taken together, our results suggest that GLR-1 is regulated in a homeostatic manner and that this effect depends on clathrin-mediated endocytosis but does not require ubiquitination of GLR-1. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Wellman 8,50 Blossom St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NINDS NIH HHS [NS32196, R01 NS035812, NS35812, R01 NS032196, R37 NS032196] NR 46 TC 28 Z9 36 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 MAR 2 PY 2004 VL 101 IS 9 BP 3190 EP 3195 DI 10.1073/pnas.0306156101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300096 PM 14981253 ER PT J AU Tegeder, I Del Turco, D Schmidtko, A Sausbier, M Feil, R Hofmann, F Deller, T Ruth, P Geisslinger, G AF Tegeder, I Del Turco, D Schmidtko, A Sausbier, M Feil, R Hofmann, F Deller, T Ruth, P Geisslinger, G TI Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE spinal cord; substance P; nitric oxide; pain ID LONG-TERM POTENTIATION; NITRIC-OXIDE SYNTHASE; METHYL-D-ASPARTATE; SOLUBLE GUANYLATE-CYCLASE; SPINAL-CORD; SMOOTH-MUSCLE; ACTIVATION; NEURONS; GMP; SENSITIZATION AB cGMP-dependent protein kinase I (PKG-I) has been suggested to contribute to the facilitation of nociceptive transmission in the spinal cord presumably by acting as a downstream target of nitric oxide. However, PKG-I activators caused conflicting effects on nociceptive behavior. In the present study we used PKG-I-/- mice to further assess the role of PKG-I in nociception. PKG-I deficiency was associated with reduced nociceptive behavior in the formalin assay and zymosan-induced paw inflammation. However, acute thermal nociception in the hot-plate test was unaltered. After spinal delivery of the PKG inhibitor, Rp-8-Br-cGMPS, nociceptive behavior of PKG-I+/+ mice was indistinguishable from that of PKG-I-/- mice. On the other hand, the PKG activator, 8-Br-cGMP (250 nmol intrathecally) caused mechanical allodynia only in PKG-I+/+ mice, indicating that the presence of PKG-I was essential for this effect. Immunofluorescence studies of the spinal cord revealed additional morphological differences. In the dorsal horn of 3- to 4-week-old PKG-I-/- mice laminae I-III were smaller and contained fewer neurons than controls. Furthermore, the density of substance P-positive neurons and fibers was significantly reduced. The paucity of substance P in laminae I-III may contribute to the reduction of nociception in PKG-I-/- mice and suggests a role of PKG-I in substance P synthesis. C1 Univ Frankfurt Klinikum, Pharmazentrum Frankfurt, D-60590 Frankfurt, Germany. Univ Frankfurt Klinikum, Inst Klin Neuroanat, D-60590 Frankfurt, Germany. Univ Tubingen, Inst Pharmazeut, D-72076 Tubingen, Germany. Tech Univ Munich, Inst Pharmakol & Toxikol, D-80802 Munich, Germany. RP Tegeder, I (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, NPRG, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM itegeder@hotmail.com RI Feil, Robert/B-8918-2014 OI Feil, Robert/0000-0002-7335-4841 NR 30 TC 58 Z9 62 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3253 EP 3257 DI 10.1073/pnas.0304076101 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300107 PM 14973199 ER PT J AU Shou, HX Bordallo, P Fan, JB Yeakley, JM Bibikova, M Sheen, J Wang, K AF Shou, HX Bordallo, P Fan, JB Yeakley, JM Bibikova, M Sheen, J Wang, K TI Expression of an active tobacco mitogen-activated protein kinase kinase kinase enhances freezing tolerance in transgenic maize SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Nicotiana protein kinase; stress tolerance; Zea mays ID PLANT COLD-ACCLIMATION; OXIDATIVE STRESS; GENE-EXPRESSION; ARABIDOPSIS TRANSCRIPTOME; FIBEROPTIC ARRAYS; LOW-TEMPERATURE; OVEREXPRESSION; PATHWAYS; IDENTIFICATION; TRANSFORMATION AB Cold acclimation is the major process that prepares plants for freezing tolerance. In addition to extensive transcription regulation by cold-inducible master transcription factors, oxidative stress signaling has been postulated to play a role in freezing tolerance. Activation of oxidative signaling through the expression of an active mitogen-activated protein kinase kinase kinase provided benefits in transgenic tobacco at freezing temperature bypassing cold acclimation. Because involvement of the mitogen-activated protein kinase cascade in oxidative stress signaling is evolutionarily conserved in eukaryotes from yeast to mammals, we tested the effect of expressing a heterologous tobacco mitogen-activated protein kinase kinase kinase (Nicotiana PK1), which can mimic H2O2 signaling, in a major cereal crop. We demonstrate that low-level but constitutive expression of the Nicotiana PK1 gene enhances freezing tolerance in transgenic maize plants that are normally frost sensitive. Our results suggest that a new molecular approach can be designed to genetically enhance freezing tolerance in important crops. C1 Iowa State Univ, Dept Agron, Plant Transformat Facil, Ames, IA 50011 USA. Illumina Inc, San Diego, CA 92121 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Wang, K (reprint author), Iowa State Univ, Dept Agron, Plant Transformat Facil, Ames, IA 50011 USA. EM kanwang@iastate.edu RI Shou, Huixia/I-3052-2015 NR 48 TC 63 Z9 85 U1 2 U2 13 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 MAR 2 PY 2004 VL 101 IS 9 BP 3298 EP 3303 DI 10.1073/pnas.0308095100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300115 PM 14960727 ER PT J AU Singh, AK Gervais, D Mueller, P Shirkhoda, A Sagar, P McCarrol, K AF Singh, AK Gervais, D Mueller, P Shirkhoda, A Sagar, P McCarrol, K TI Cardiac arrest: abdominal CT imaging features SO ABDOMINAL IMAGING LA English DT Article DE cardiac arrest; contrast reflux; dense abdominal veins; shock AB We report computed tomographic findings of two unusual cases of sudden cardiac arrest. The imaging features documented include reflux of contrast into the abdomen as indicated by opacification of renal veins, hepatic veins, inferior vena cava, and hepatic and renal parenchyma. The reflux of contrast into the portal vein in one patient has not been described in the literature. The thoracic findings were reflux of contrast into the coronary sinus, nonopacificaton of the left ventricle with intravenous contrast, and lack of cardiac motion artifact. C1 Long Isl Coll Hosp, Dept Internal Med, Brooklyn, NY 11201 USA. William Beaumont Hosp, Dept Radiol, Royal Oak, MI 48073 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Sagar, P (reprint author), Long Isl Coll Hosp, Dept Internal Med, Brooklyn, NY 11201 USA. EM pallaviajay@hotmail.com NR 6 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAR-APR PY 2004 VL 29 IS 2 BP 177 EP 179 DI 10.1007/s00261-003-0120-0 PG 3 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 803TD UT WOS:000220252500008 PM 15290943 ER PT J AU Mischoulon, D Beresin, EV AF Mischoulon, D Beresin, EV TI "The matrix": An allegory of the psychoanalytic journey SO ACADEMIC PSYCHIATRY LA English DT Article AB Objective: "The Matrix" has been a huge commercial and critical success and has spawned a series of books and essays exploring the philosophical and religious themes in the story. Methods: The authors propose is that "The Matrix" can be, interpreted as an allegory for an individual's journey into spiritual and mental health, achieved by overcoming one's intrapsychic conflicts with the help of psychodynamic psychotherapy or psychoanalysis. Results: Neo's story parallels the journey undertaken by the individual who chooses to enter psychotherapy and illustrates several themes of analytic psychotherapy, its benefits, and liabilities. Conclusion: The movie may therefore serve as a teaching tool for psychiatric residents about the goals, functions, and intricacies of psychodynamic psychotherapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp McLean Hosp, Child & Adolescent Psychiat Residency Training Pr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, WAC-812,15 Parkman St, Boston, MA 02114 USA. EM dmischoulon@partners.org NR 32 TC 2 Z9 2 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SPR PY 2004 VL 28 IS 1 BP 71 EP 77 DI 10.1176/appi.ap.28.1.71 PG 7 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 816KA UT WOS:000221107600012 PM 15140812 ER PT J AU Villar, J Kacmarek, RM Hedenstierna, G AF Villar, J Kacmarek, RM Hedenstierna, G TI From ventilator-induced lung injury to physician-induced lung injury: Why the reluctance to use small tidal volumes? SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Review ID ACUTE RESPIRATORY-DISTRESS; END-EXPIRATORY PRESSURE; RECEIVING MECHANICAL VENTILATION; EVIDENCE-BASED MEDICINE; CLINICAL-PRACTICE; CRITICAL-CARE; MODEL; TRIAL C1 Hosp Univ NS de Candelaria, Tenerife, Canary Islands, Spain. St Michaels Hosp, Res Ctr, Toronto, ON M5B 1W8, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Uppsala Univ, Dept Med Sci, Stockholm, Sweden. RP Villar, J (reprint author), Hosp NS de Candelaria, Res Inst, Carretera Rosario S-N, Santa Cruz de Tenerife 38010, Canary Islands, Spain. EM jesus.villar@canarias.org NR 34 TC 26 Z9 26 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD MAR PY 2004 VL 48 IS 3 BP 267 EP 271 DI 10.1111/j.0001-5172.2004.0340.x PG 5 WC Anesthesiology SC Anesthesiology GA 803SS UT WOS:000220251400001 PM 14982557 ER PT J AU Norris, PJ Moffett, HF Brander, C Allen, TM O'Sullivan, KM Cosimi, LA Kaufmann, DE Walker, BD Rosenberg, ES AF Norris, PJ Moffett, HF Brander, C Allen, TM O'Sullivan, KM Cosimi, LA Kaufmann, DE Walker, BD Rosenberg, ES TI Fine specificity and cross-clade reactivity of HIV type 1 Gag-specific CD4(+) T cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PEPTIDE-FLANKING RESIDUES; AMINO-ACID-RESIDUES; PLASMODIUM-FALCIPARUM; POTENTIAL MECHANISM; CYCLOPHILIN-A; RESPONSES; RECEPTOR; EPITOPE; RECOGNITION AB Despite growing evidence that HIV-1-specific CD4(+) T helper (Th) cells may play a role in the control of viremia, discrete Th cell epitopes remain poorly defined. Furthermore, it is not known whether Th cell responses generated using vaccines based on clade B virus sequences will elicit immune responses that are effective in regions of the world where non-clade B viruses predominate. To address these issues we isolated CD4(+) T cell clones from individuals with vigorous HIV-1-specific Th cell responses and identified the minimum epitopes recognized. The minimum peptide length required for induction of CD4(+) T cell proliferation, IFN-gamma secretion, and cytolytic activity ranged from 9 to 16 amino acids in the five epitopes studied. Cross-clade recognition of the defined epitopes was examined for variant peptides from clades A, B, C, D, and AE. Over half the variant epitopes (17 of 32) exhibited impaired recognition, defined as less than 50% of the IFN-gamma secretion elicited by B clade consensus sequence. There was no evidence for antagonistic activity mediated by the variant peptides, and despite strong responses there was no escape of autologous virus from Th responses in the epitopes we studied. Abrogated recognition of variant CD4(+) T cell epitopes presents a potential obstacle to vaccine development. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Norris, PJ (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Room 5022, Charlestown, MA 02129 USA. EM pnorris@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [AI40873, K08 AI001698, K08 AI001698-04, R01 AI040873, R21 AI040873, AI01698] NR 62 TC 24 Z9 24 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2004 VL 20 IS 3 BP 315 EP 325 DI 10.1089/088922204322996554 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 811XS UT WOS:000220805200009 PM 15117455 ER PT J AU Marinkovic, K Halgren, E Maltzman, I AF Marinkovic, K Halgren, E Maltzman, I TI Effects of alcohol on verbal processing: An event-related potential study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; verbal processing; event-related potentials; N400; electrodermal activity ID DEPTH-RECORDED POTENTIALS; WORD FORM AREA; BRAIN POTENTIALS; SPATIOTEMPORAL STAGES; AUDITORY-STIMULI; TEMPORAL-LOBE; ACUTE ETHANOL; REPETITION; MEMORY; INTOXICATION AB Background: Behavioral studies suggest that alcohol intoxication impairs the speed and accuracy of word recognition and categorization, but alcohol's effects on the brain during verbal cognitive processing are not adequately understood. Using event-related potentials (ERP) and a word-recognition paradigm, this study investigated the effects of alcohol intoxication on prelexical, semantic, and mnemonic aspects of verbal processing. Methods: Concurrent measures of ERPs and skin conductance responses were obtained in a word-repetition priming task and permitted a comparison of the effects of alcohol on the central and autonomic physiologic systems. Social drinkers participated in all four cells of the within-subjects balanced placebo design, in which the effects of alcohol and information as to the beverage content (expectancy) were manipulated. The average peak blood alcohol level peaked at 0.045%. Results: None of the manipulations affected behavioral performance, and expectancy had no effect on any of the measures. In contrast, alcohol ingestion attenuated the temporoparietal N180, suggesting an impairment in prelexical pattern-recognition processes. Alcohol significantly increased the amplitude of N450 and the latency of P580, particularly on trials evoking sympathetic arousal as measured with skin conductance responses. Conclusions: Although behavioral measures were unaffected, ERPs showed that a moderately low alcohol dose affected verbal processing during both early, prelexical and late, semantic stages. Alcohol significantly increased the difficulty of semantic access and integration, as reflected in larger N450 amplitude and longer P580 latency. This effect was particularly prominent on arousal-related trials, suggesting that alcohol impairs processes that modulate cognitive functioning. The lack of an interaction between the factors of repetition and beverage suggests that a moderately low alcohol dose exerts these effects via the semantic and integration systems rather than via memory processes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. INSERM, F-13258 Marseille, France. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Marinkovic, K (reprint author), MGH, NMR Ctr, 149 13th St,Room 2301, Charlestown, MA 02129 USA. EM xenia@nmr.mgh.harvard.edu FU NIAAA NIH HHS [K01 AA013402, AA13402]; NINDS NIH HHS [NS18741, R01 NS018741] NR 84 TC 16 Z9 17 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2004 VL 28 IS 3 BP 415 EP 423 DI 10.1097/01.ALC.0000117828.88597.80 PG 9 WC Substance Abuse SC Substance Abuse GA 808CQ UT WOS:000220547600007 PM 15084899 ER PT J AU Bradley, KA Kivlahan, DR Zhou, XH Sporleder, JL Epler, AJ McCormick, KA Merrill, JO McDonell, MB Fihn, SD AF Bradley, KA Kivlahan, DR Zhou, XH Sporleder, JL Epler, AJ McCormick, KA Merrill, JO McDonell, MB Fihn, SD TI Using alcohol screening results and treatment history to assess the severity of at-risk drinking in Veterans Affairs primary care patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol screening; alcohol drinking; primary care ID DISORDERS IDENTIFICATION TEST; RANDOMIZED CONTROLLED TRIAL; BRIEF PHYSICIAN ADVICE; TEST AUDIT; PROBLEM DRINKERS; BRIEF INTERVENTIONS; CONSUMPTION; QUESTIONNAIRES; DEPENDENCE; MORTALITY AB Background: Primary care providers need, practical methods for managing patients who screen positive for at-risk drinking. We evaluated whether scores on brief alcohol screening questionnaires and patient reports of prior alcohol treatment reflect the severity of recent problems due to drinking. Methods: Veterans Affairs general medicine outpatients who screened positive for at-risk drinking were mailed questionnaires that included the Alcohol Use Disorders Identification Test (AUDIT) and a question about prior alcohol treatment or participation in Alcoholics Anonymous ("previously treated"). AUDIT questions 4 through 10 were used to measure past-year problems due to drinking (PYPD). Cross-sectional analyses compared the prevalence of PYPD and mean Past-Year AUDIT Symptom Scores (0-28 points) among at-risk drinkers with varying scores on the CAGE (0-4) and AUDIT-C (0-12) and varying treatment histories. Results: Of 7861 male at-risk drinkers who completed questionnaires, 33.9% reported PYPD. AUDIT-C scores were more strongly associated with Past-Year AUDIT Symptom Scores than the CAGE (p < 0.0005). The prevalence of PYPD increased from 33% to 46% over the range of positive CAGE scores but from 29% to 77% over the range of positive AUDIT-C scores. Among subgroups of at-risk drinkers with the same screening scores, patients who reported prior treatment were more likely than never-treated at-risk drinkers to report PYPD and had higher mean Past-Year AUDIT Symptom Scores (p < 0.0005). We propose a simple method of risk-stratifying patients using AUDIT-C scores And alcohol treatment histories. Conclusions: AUDIT-C scores combined with one question about prior alcohol treatment can help estimate the severity of PYPD among male Veterans Affairs outpatients. C1 VA Puget Sound Hlth Care Syst, HSR&D 152, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, HSR&D 152, NW Hlth Serv Res & Dev Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. EM willi@u.washington.edu FU NIAAA NIH HHS [K23AA00313] NR 39 TC 47 Z9 48 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2004 VL 28 IS 3 BP 448 EP 455 DI 10.1097/01.ALC.0000117893.38108.38 PG 8 WC Substance Abuse SC Substance Abuse GA 808CQ UT WOS:000220547600011 PM 15084903 ER PT J AU Bennett, GG Merritt, MM Edwards, CL Sollers, JJ AF Bennett, GG Merritt, MM Edwards, CL Sollers, JJ TI Perceived racism and affective responses to ambiguous interpersonal interactions among African American men SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article DE racism; discrimination; emotions; stress; ethnicity ID CARDIOVASCULAR REACTIVITY; DISCRIMINATION AB The current study examined affective responses to ambiguous interpersonal interactions containing both ambiguous and overtly racist content. Participants included 74 African American males (ages 18-47), half of whom heard a depiction of a negative social interaction with blatantly racist content (BRC). The remaining participants heard a similar scenario containing no racist content (NRC). Negative affect scores were higher for those in the BRC group, yet individuals in the ambiguous (NRC) condition who reported perceptions of racism in the scenario showed greater negative affect reactivity than those who saw no racism in the scenario. Among those in the NRC group, self-reported past experiences with racial discrimination moderated the effect of perceived racism on negative affect. The authors conclude that the perception of racial discrimination, in particular when evaluating ambiguous situations, may have profound affective consequences for Black men. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. Duke Univ, Dept Med, Div Hematol, Durham, NC 27706 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 27 Z9 27 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD MAR PY 2004 VL 47 IS 7 BP 963 EP 976 DI 10.1177/0002764203261070 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 772QZ UT WOS:000188853900007 ER PT J AU Hoffman, JIE Kaplan, S Liberthson, RR AF Hoffman, JIE Kaplan, S Liberthson, RR TI Prevalence of congenital heart disease SO AMERICAN HEART JOURNAL LA English DT Review ID VENTRICULAR SEPTAL-DEFECT; AORTIC-VALVE-REPLACEMENT; PULMONARY VENOUS CONNECTION; TERM FOLLOW-UP; PATENT DUCTUS-ARTERIOSUS; NATURAL-HISTORY; GREAT VESSELS; UNIVENTRICULAR HEART; SURGICAL-CORRECTION; TRICUSPID-VALVE AB Background Today most patients with congenital heart disease survive childhood to be cared for by adult cardiologists. The number of physicians that should be trained to manage these lesions is unknown because we do not know the number of patients. Methods To answer this question, the expected numbers of infants with each major type of congenital heart defect born in each 5-year period since 1940 were estimated from birth rates and incidence. The numbers expected to survive with or without treatment were estimated from data on natural history and the results of treatment. Finally, lesions were categorized as simple, moderate, or complex, based on the amount of expertise in management needed for optimal patient care. Results From 1940 to 2002, about 1 million patients with simple lesions, and half that number each with moderate and complex lesions, were born in the United States. If all were treated, there would be 750,000 survivors with simple lesions, 400,000 with moderate lesions, and 180,000 with complex lesions; in addition, there would be 3,000,000 subjects alive with bicuspid aortic valves. Without treatment, the survival in each group would be 400,000,220,000, and 30,000, respectively. The actual numbers surviving will be between these 2 sets of estimates. Conclusions Survival of patients with congenital heart disease, treated or untreated, is expected to produce large numbers of adults with congenital disease, and it is likely that many more adult cardiologists will need to be trained to manage moderate and complex congenital lesions. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Ahmanson UCLA Adult Congenital Heart Dis Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Ahmanson UCLA Adult Congenital Heart Dis Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Ahmanson UCLA Adult Congenital Heart Dis Ctr, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Hoffman, JIE (reprint author), Univ Calif San Francisco, Dept Pediat, Box 0544,Room M1331,505 Parnassus Ave, San Francisco, CA 94143 USA. EM jhoffman@pedcard.ucsf.edu FU NHLBI NIH HHS [HL 25847] NR 112 TC 309 Z9 327 U1 1 U2 17 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2004 VL 147 IS 3 BP 425 EP 439 DI 10.1016/j.ahj.2003.05.003 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807ZM UT WOS:000220539400013 PM 14999190 ER PT J AU Kirtane, AJ Bui, A Murphy, SA Barron, HV Gibson, CM AF Kirtane, AJ Bui, A Murphy, SA Barron, HV Gibson, CM TI Association of peripheral neutrophilia with adverse angiographic outcomes in ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BLOOD-CELL COUNT; TIMI FRAME COUNT; UNSTABLE ANGINA; ISCHEMIA/REPERFUSION INJURY; CLINICAL-OUTCOMES; THROMBOLYSIS; REPERFUSION; MORTALITY; ISCHEMIA; FLOW AB We hypothesized that absolute and relative neutrophilia would be associated with adverse angiographic outcomes in the 394 patient Limitation of Myocardial Infarction Following Thrombolysis in Acute Myocardial Infarction (LIMIT) Acute Myocardial Infarcion (AMI) trial of fibrinolysis in ST-elevation myocardial infarction. The mean neutrophil count was 7.9 x 10(9)/L, with a mean neutrophil percentage of 72%. Patients with time from symptom onset to fibrinolytic treatment more than the median (2.7 hours) had a higher neutrophil count and percentage of neutrophils than patients with shorter time to treatment. Patients with a closed infarct-related artery at 90 minutes (Thrombolysis In Myocardial Infarction [TIMI] grade 0/1 flow) had higher neutrophil counts (8.8 +/- 3.8. vs, 7.6 +/- 3.0, p = 0.02) but no difference in the percentage of neutrophils than patients with an open artery. Higher neutrophil counts were also mildly correlated with longer corrected TIMI, frame counts (CTFC) in the infarct-related artery (r = 0.14, p = 0.02). Patients with impaired myocardial perfusion by TIMI myocardial perfusion grade (TMPG) had a greater percentage of neutrophils (73.2 +/- 10.7% for TMPG 0/1 vs 69.9 +/- 12.6% for TMPG -2/3, p = 0.047) but no detectable difference in neutrophil counts (8.2 +/- 3.3 vs 7.7 +/- 2.9, P = 0.24). There were no significant associations between other indexes in the cell differential and angiographic or clinical outcomes. Higher neutrophil counts remained independently associated with both closed arterues and CTFC in multivariable models controlling for, age, left anterior descending artery infarct location, time to treatment, and pulse and blood pressure on admission. A greater percentage of neutrophils remained independently associated with impaired microvascular perfusion in a similar multivariable model. In patients with ST-elevation myocardial infarction, absolute and relative neutrophilia were associated with impaired epicardial and microvascular perfusion. (C) 2004 by Excerpta Medica, Inc. C1 TIMI Data Coordinating Ctr, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA. EM mgibson@perfuse.org NR 35 TC 60 Z9 63 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2004 VL 93 IS 5 BP 532 EP 536 DI 10.1016/j.amjcard.2003.11.013 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 801DE UT WOS:000220075800002 PM 14996574 ER PT J AU Cole, JA Cook, SF Sands, BE Ajene, AN Miller, DP Walker, AM AF Cole, JA Cook, SF Sands, BE Ajene, AN Miller, DP Walker, AM TI Occurrence of colon ischemia in relation to irritable bowel syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID WOMEN; ALOSETRON; DIARRHEA; CRITERIA; COLITIS; TRIAL AB Objective: In November 2000, alosetron HCI (Lotronex(R)), a treatment for irritable bowel syndrome (IBS), was removed from the U.S. market in part because of the occurrence of colon ischemia in treated patients. Since the relation between colon ischemia and IBS is poorly understood, we evaluated the incidence of colon ischemia among people with and without IBS. Methods: Using medical claims data from a large health care organization in the United States, we identified 87,449 people with an IBS diagnosis between January 1995 and December 1999. We calculated age- and sex-specific incidence rates in the general population and in IBS patients. Results: There were 740 cases of colon ischemia during 8.5 million person-years of observation in 5.4 million persons. The crude incidence rate was 42.8 cases per 100,000 person-years for IBS patients. By comparison, the incidence rate was 7.2 per 100,000 person-years in the general population. After adjustment for age, sex, and calendar year, the incidence of colon ischemia in people with IBS was 3.4 times higher than in persons without (95% CI 2.6-4.5). Conclusions: Rates of colon ischemia among patients carrying a diagnosis of IBS are substantially higher than in the general population. Colon ischemia, though unusual in IBS patients, may nonetheless constitute a distinct part of the IBS natural history. Alternatively, it may be a consequence of therapy, or a manifestation of other bowel pathology that is sometimes confused with IBS. C1 Ingenix Epidemiol, Newton, MA 02466 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walker, AM (reprint author), Ingenix Epidemiol, 275 Grove St,Suite 3-120, Newton, MA 02466 USA. FU NIDDK NIH HHS [5K23 DK02850-03] NR 12 TC 71 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2004 VL 99 IS 3 BP 486 EP 491 DI 10.1111/j.1572-0241.2004.04097.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805QR UT WOS:000220381300017 PM 15056090 ER PT J AU Lleo, A Berezovska, O Growdon, JH Hyman, BT AF Lleo, A Berezovska, O Growdon, JH Hyman, BT TI Clinical, pathological, and biochemical spectrum of Alzheimer disease associated with PS-1 mutations SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Review ID AMYLOID-BETA-PROTEIN; GAMMA-SECRETASE CLEAVAGE; AGE-OF-ONSET; COTTON WOOL PLAQUES; PRESENILIN-1 MUTATION; SPASTIC PARAPARESIS; INTRACELLULAR DOMAIN; MISSENSE MUTATIONS; LEWY BODIES; IN-VIVO AB Three genes have been implicated in the etiology of early-onset autosomal-dominant Alzheimer disease (AD): the amyloid precursor protein, the presenilin-1, and presenilin-2 genes. Approximately half of autosomal-dominant AD cases are associated with mutations in the presenilin-1 (PS-1) gene on the long arm of Chromosome 14. Marked allelic heterogeneity characterizes families with PS-1 gene mutations; more than 100 different mutations have been found in independent families thus far With the exception of age at onset, the clinical phenotype is similar to late-onset AD, although some rare specific phenotypes have been described. These mutations lead to enhanced deposition of total Abeta and Abeta42 (but not Abeta40) in the brain, compared with sporadic AD. There is a considerable heterogeneity in the histological profiles among brains from patients with different mutations, and although some lead to predominantly parenchymal deposition of Abeta in the form of diffuse and cored plaques, others show predominantly vascular deposition, with severe amyloid angiopathy. Only some mutations are associated with enhanced neurofibrillary tangle formation and increased neuronal loss compared with sporadic AD. However, there is an important clinical and pathological variability even among family members with the same mutation, which suggests the involvement of other genetic or environmental factors that modulate the clinical expression of the disease. This represents a valuable model for identifying such factors and has potential implications for the development of new therapeutic strategies for delaying disease onset. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, Rm 2009,114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org FU NIA NIH HHS [AG15379] NR 127 TC 56 Z9 59 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR-APR PY 2004 VL 12 IS 2 BP 146 EP 156 DI 10.1176/appi.ajgp.12.2.146 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 776MQ UT WOS:000189120100006 PM 15010344 ER PT J AU Tsuang, DW DiGiacomo, L Bird, TD AF Tsuang, DW DiGiacomo, L Bird, TD TI Familial occurrence of dementia with Lewy bodies SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PARKINSONS-DISEASE; BODY-DISEASE; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; VASCULAR DEMENTIA; PATHOLOGY; DIAGNOSIS; LOCUS; DLB; CORRELATE AB Objective: The authors investigated the validity of the designation ''familial dementia with Lewy bodies (DLB)" by evaluating the clinical, neuropathological, and genetic characteristics of previously reported families exhibiting both familial parkinsonism and dementia. Methods: Several families, including multiple individuals with parkinsonism as well as prominent dementia, were identified through a literature search. Selected families bad at least one member with dementia with autopsy evidence of neocortical and/or limbic Lewy-body (LB) pathology. Clinical and neuropathological evidence from reports of families with prominent dementia as well as parkinsonism was reviewed to further define familial DLB. Results: All selected families bad at least one affected individual with dementia and autopsy-proven DLB. Therefore, these families might be considered examples of familial DLB. Individuals in the first six families typically presented with parkinsonian features, whereas cognitive decline did not appear until years later In contrast, in the other six families, affected individuals typically presented with cognitive decline, and parkinsonism developed later Conclusions: Families exist in which one or more persons meet both clinical and neuropathological criteria for DLB. They differ as to whether the signs of parkinsonism precede or follow signs of dementia. It remains to be determined whether this clinical distinction is biologically important. Susceptibility to developing LB pathology may be determined by the interaction between genetic predisposition and environmental risk factors. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr 116, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med Genet, Seattle, WA 98195 USA. RP Tsuang, DW (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr 116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NINDS NIH HHS [R01 NS048595] NR 40 TC 15 Z9 15 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR-APR PY 2004 VL 12 IS 2 BP 179 EP 188 DI 10.1176/appi.ajgp.12.2.179 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 776MQ UT WOS:000189120100009 PM 15010347 ER PT J AU Hayes-Lattin, B Seipel, TJ Gatter, K Heinrich, MC Maziarz, RT AF Hayes-Lattin, B Seipel, TJ Gatter, K Heinrich, MC Maziarz, RT TI Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE anemia; pure red cell aplasia; parvovirus B19; allogeneic stem cell transplantation ID PERIPHERAL-BLOOD; ANEMIA; RECIPIENT; ANTIGEN; THERAPY; PATIENT AB Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed. Am. J. Hematol. 75:142-145, 2004. (C) 2004 Wiley-Liss, Inc. C1 Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Adult Bone Marrow Transplanat Program, Portland, OR 97239 USA. OHSU Canc Inst, Portland, OR USA. Portland Vet Affairs Med Ctr, Div Hematol & Med Oncol, Portland, OR USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Hayes-Lattin, B (reprint author), Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Adult Bone Marrow Transplanat Program, Mailcode L586,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM hayeslat@ohsu.edu NR 22 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2004 VL 75 IS 3 BP 142 EP 145 DI 10.1002/ajh.10474 PG 4 WC Hematology SC Hematology GA 779TR UT WOS:000189317500005 PM 14978694 ER PT J AU Ramaswawy, S AF Ramaswawy, S TI Microarrays for an integrative genomics SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Book Review C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Ramaswawy, S (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD MAR-APR PY 2004 VL 16 IS 2 BP 174 EP 175 DI 10.1002/ajhb.20009 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 800CL UT WOS:000220006400010 ER PT J AU Glassman, PA Good, CB Kelley, ME Bradley, M Valentino, M AF Glassman, PA Good, CB Kelley, ME Bradley, M Valentino, M TI Physician satisfaction with formulary policies: Is it access to formulary or nonformulary drugs that matters most? SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID COST-CONTAINMENT; BENEFIT PLANS AB Objective: To assess physician satisfaction with Department of Veterans Affairs (VA) formulary policies and to examine the correlation between physician satisfaction and perceived access to formulary and nonformulary medications. Study Design: Cross-sectional survey with specific questions on access to formulary and nonformulary medications. Statistical analyses. included assessment of associations between physician satisfaction and various measures of access. Participants and Methods: Initial sample of 4015 staff physicians working in VA healthcare facilities. Responses were received from 1812 (49%) of the 3682 physicians in the final eligible sample population. Results: Most clinicians (72%) reported that their local formulary covered more than 90% of the medications they wanted to prescribe. Most (71%) agreed that drug restrictions were important to contain costs, and 86% agreed that it was important for VA to choose "best-value" drugs. Respondents reported an 89% approval rate for nonformulary drugs, though 31% indicated that approvals routinely took 3 or more days. We found strong associations between physician satisfaction and self-reported approval rates for nonformulary drugs (P = .001), timely approval of nonformulary requests (P < .001), and percentage of nonformulary prescriptions as a proportion of overall prescriptions at a regional level (P < .01). There was no significant correlation between physician satisfaction and number of medications added to regional formularies or with drug costs per unique patient. Conclusions: VA physicians were generally supportive of VA formulary policies including choosing best-value drugs to control pharmaceutical expenditures. Nevertheless, access to nonformulary drugs and timely approval of requests for nonformulary medications were strong predictors of clinician satisfaction and Support for cost-containment measures. C1 VA Greater Los Angeles, W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Healthcare Syst,Dept Vet Affairs, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RAND Corp, Survey Res Ctr, Washington, DC USA. Vet Affairs Hosp, Pharm Benefits Management Strateg Healthcare Grp, Hines, IL USA. RP Glassman, PA (reprint author), VA Greater Los Angeles, W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Healthcare Syst,Dept Vet Affairs, 111G,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. EM peter.glassman@med.va.gov NR 27 TC 9 Z9 9 U1 0 U2 3 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAR PY 2004 VL 10 IS 3 BP 209 EP 216 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 803IM UT WOS:000220224800006 PM 15032258 ER PT J AU Huisman, TAGM Schwamm, LH Schaefer, PW Koroshetz, WJ Shetty-Alva, N Ozsunar, Y Wu, O Sorensen, AG AF Huisman, TAGM Schwamm, LH Schaefer, PW Koroshetz, WJ Shetty-Alva, N Ozsunar, Y Wu, O Sorensen, AG TI Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Neuroradiology CY MAY 11-17, 2002 CL VANCOUVER, CANADA SP Amer Soc Neuroradiol ID TRAUMATIC BRAIN-INJURY; HEAD-INJURY; WATER-DIFFUSION; MR; ANISOTROPY; DAMAGE; STROKE; CT AB BACKGROUND AND PURPOSE: Multiple biomarkers are used to quantify the severity of traumatic brain injury (TBI) and to predict outcome. Few are satisfactory. CT and conventional MR imaging underestimate injury and correlate poorly with outcome. New MR imaging techniques, including diffusion tensor imaging (DTI), can provide information about brain ultrastructure by quantifying isotropic and anisotropic water diffusion. Our objective was to determine if changes in anisotropic diffusion in TBI correlate with acute Glasgow coma scale (GCS) and/or Rankin scores at discharge. METHODS: Twenty patients (15 male, five Female; mean age, 31 years) were evaluated. Apparent diffusion coefficients (ADCs) and fractional anisotropy (FA) values were measured at multiple locations and correlated with clinical scores. Results were compared with those of 15 healthy control subjects. RESULTS: ADC values were significantly reduced within the splenium (Delta18%, P = .001). FA values were significantly reduced in the internal capsule (Delta14%; P < .001) and splenium (Delta16%; P = .002). FA values were significantly correlated with GCS (r = 0.65-0.74; P < .001) and Rankin (r = 0.68-0.71; P < .001) scores for the internal capsule and splenium. The correlation between FA and clinical markers was better than for the corresponding ADC values. No correlation was found between ADC of the internal capsule and GCS/Rankin scores. CONCLUSION: DTI reveals changes in the white matter that are correlated with both acute GCS and Rankin scores at discharge. DTI may be a valuable biomarker for the severity of tissue injury and a predictor for outcome. C1 Univ Zurich, Childrens Hosp, Dept Radiol, CH-8032 Zurich, Switzerland. Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Huisman, TAGM (reprint author), Univ Zurich, Childrens Hosp, Dept Radiol, Steinweisstr 75, CH-8032 Zurich, Switzerland. OI Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [P41 RR 14075]; NINDS NIH HHS [R01 NS 38477] NR 26 TC 276 Z9 296 U1 0 U2 20 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2004 VL 25 IS 3 BP 370 EP 376 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 804TR UT WOS:000220321500005 PM 15037457 ER PT J AU Abraham, EJ Kodama, S Lin, JC Ubeda, M Faustman, DL Hebener, JF AF Abraham, EJ Kodama, S Lin, JC Ubeda, M Faustman, DL Hebener, JF TI Human pancreatic islet-derived progenitor cell engraftment in immunocompetent mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEURAL STEM-CELLS; TRANSPLANTATION TOLERANCE; MIXED CHIMERISM; IN-VITRO; DENDRITIC CELLS; ADULT-MOUSE; MARROW; DIFFERENTIATE; MICROCHIMERISM; ACCEPTANCE AB The potential for the use of stem/progenitor cells for the restoration of injured or diseased tissues has garnered much interest recently, establishing a new field of research called regenerative medicine. Attention has been focused on embryonic stem cells derived from human fetal tissues. However, the use of human fetal tissue for research and transplantation is controversial. An alternative is the isolation and utilization of multipotent stem/progenitor cells derived from adult donor tissues. We have previously reported on the isolation, propagation, and partial characterization of a population of stem/progenitor cells isolated from the pancreatic islets of Langerhans of adult human donor pancreata. Here we show that these human adult tissue-derived cells, nestin-positive islet-derived stem/progenitor cells, prepared from human adult pancreata survive engraftment and produce tissue chimerism when transplanted into immunocompetent mice either under the kidney capsule or by systemic injection. These xenografts seem to induce immune tolerance by establishing a mixed chimerism in the mice. We propose that a population of stem/progenitor cells isolated from the islets of the pancreas can cross xenogeneic transplantation immune barriers, induce tissue tolerance, and grow. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Diabet Unit, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunobiol Lab, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hebener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Diabet Unit, 55 Fruit St,WEL 320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [R01 DK055365, R21 DK 60125, R01 DK55365, R21 DK060125] NR 44 TC 38 Z9 41 U1 0 U2 2 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 MAR PY 2004 VL 164 IS 3 BP 817 EP 830 DI 10.1016/S0002-9440(10)63170-7 PG 14 WC Pathology SC Pathology GA 777FC UT WOS:000189164300008 PM 14982836 ER PT J AU Yang, CW Ionescu-Tiba, V Burns, K Gadd, M Zukerberg, L Louis, DN Sgroi, D Schmidt, EV AF Yang, CW Ionescu-Tiba, V Burns, K Gadd, M Zukerberg, L Louis, DN Sgroi, D Schmidt, EV TI The role of the cyclin D1-dependent kinases in ErbB2-mediated breast cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RETINOBLASTOMA PROTEIN; TRANSGENIC MICE; EXPRESSION; D1; OVEREXPRESSION; P16(INK4A); CELLS; TRANSFORMATION; GLIOBLASTOMAS; FLAVOPIRIDOL AB Intact cyclin D1 functions are essential for transformation by erbB2 in tissue culture and murine models. Because cyclin D1 may alter cell proliferation through a variety of mechanisms, we used transgenic models and human tumor samples to particularly address the role of cyclin D1-cyclin-dependent kinases in transformation by erbB2. The p16 tumor suppressor specifically blocks cyclin-dependent kinase 4 and 6 activity. Here we show that an MMTV-p16 transgene blocked tumorigenesis by erbB2, demonstrating that deregulation of the cyclin-dependent kinase partner of cyclin D1 is an essential target of erbB2. ErbB2 overexpression was a determining factor in deregulation of cyclin Dl-cdk4/6 interactions because neither transgenic cyclin D1 nor loss of p16 accelerated tumorigenesis in MMTV-erbB2-transgenic mice. ErbB2 was also a deciding factor in deregulation of cyclin D1-cdk4/6 in human tumors because no loss of pRb or p16 was found in tumors overexpressing erbB2, although erbB2-negative invasive breast adenocarcinomas frequently lacked expression of p16 or pRb. We conclude that deregulation of cyclin D1-Cdk4/6 interactions is a critical target of erbB2 function in human and mouse breast tumors, and erbB2's overexpression may be sufficient to deregulate cyclin D1-cdk4/6 activity in breast cancer. C1 Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Ottawa Hosp, Ottawa, ON, Canada. Massachusetts Gen Hosp E, Mol Pathol Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA069069, R01 CA69069, P50 CA089393, P50 CA89393] NR 30 TC 23 Z9 25 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 MAR PY 2004 VL 164 IS 3 BP 1031 EP 1038 DI 10.1016/S0002-9440(10)63190-2 PG 8 WC Pathology SC Pathology GA 777FC UT WOS:000189164300028 PM 14982856 ER PT J AU Andrikopoulos, S Hull, RL Verchere, CB Wang, F Wilbur, SM Wight, TN Marzban, L Kahn, SE AF Andrikopoulos, S Hull, RL Verchere, CB Wang, F Wilbur, SM Wight, TN Marzban, L Kahn, SE TI Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE amylin; euglycemic hyperinsulinemic clamp; insulin sensitivity ID IN-VITRO; DIABETES-MELLITUS; FIBRIL FORMATION; CELL-LINE; MICE; AMYLIN; IAPP; LANGERHANS; PROINSULIN; PEPTIDES AB Pancreatic amyloid is found in patients with insulinomas and type 2 diabetes. To study mechanisms of islet amyloidogenesis, we produced transgenic mice expressing the unique component of human islet amyloid, human islet amyloid polypeptide (hIAPP). These mice develop islet amyloid after 12 mo of high-fat feeding. To determine whether we could accelerate the rate of islet amyloid formation, we crossbred our hIAPP transgenic animals with RIP-Tag mice that develop islet tumors and die at 12 wk of age from hypoglycenia. At 12 wk of age, this new line of hIAPPXRIP-Tag mice was heavier (29.7 +/- 1.0 vs. 25.0 +/- 1.3 g, P < 0.05) and had increased plasma glucose levels (4.6 +/- 0.4 vs. 2.9 +/- 0.6 mmol/l, P < 0.05) compared with littermate RIP-Tag mice. However, the hIAPPXRIP-Tag mice did not display islet amyloid or amyloid fibrils despite high circulating hIAPP levels (24.6 +/- 7.0 pmol/l). Interestingly, hIAPPXRIP-Tag mice had a longer life span than RIP-Tag mice (121 +/- 8 vs. 102 +/- 5 days, P < 0.05). This increase in life span in hIAPPXRIP-Tag was positively correlated with body weight (r = 0.48, P < 0.05) and was associated with decreased insulin sensitivity compared with RIP-Tag mice. hIAPPXRIP-Tag mice did not develop amyloid during their 4-mo life span, suggesting that increased hIAPP secretion is insufficient for islet amyloid formation within such a short time. However, hIAPPXRIP-Tag mice did have an increase in life span that was associated with insulin resistance, suggesting that hIAPP has extrapancreatic effects, possibly on peripheral glucose metabolism. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98109 USA. Univ Washington, Hope Heart Inst, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Seattle, WA 98108 USA. British Columbia Res Inst Childrens & Womens Hlth, Vancouver, BC V5Z 4H4, Canada. RP Kahn, SE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 151,1660 S Columbian Way, Seattle, WA 98109 USA. EM skahn@u.washington.edu FU NIDDK NIH HHS [DK-50703, DK-17047] NR 48 TC 3 Z9 3 U1 0 U2 1 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 MAR PY 2004 VL 286 IS 3 BP E418 EP E424 DI 10.1152/ajpendo.00137.2003 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 776XP UT WOS:000189144900013 PM 14613923 ER PT J AU Reeve, JR Wu, SV Keire, DA Faull, K Chew, P Solomon, TE Green, GM Coskun, T AF Reeve, JR Wu, SV Keire, DA Faull, K Chew, P Solomon, TE Green, GM Coskun, T TI Differential bile-pancreatic secretory effects of CCK-58 and CCK-8 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cholecystokinin ID CHOLECYSTOKININ CCK; HUMAN-PLASMA; RAT; RECEPTORS; BINDING; ACINI; FORM; RADIOIMMUNOASSAY; BIOACTIVITY; INTESTINE AB In this work, we 1) synthesized rat CCK-58, 2) determined the amounts and forms of rat CCK in whole blood after stimulation of its release by casein, 3) determined the potency of CCK-8 and CCK-58 peptides to displace labeled CCK-8 from CCKA and CCKB receptors transfected into Chinese hamster ovary (CHO) cells, and 4) examined the biological actions of CCK-8 and rat CCK-58 in an anesthetized rat model. CCK-58 was the only detected endocrine form of CCK in rat blood. Synthetic rat CCK-58 was less potent than CCK-8 for displacing the label from CCKA and CCKB receptors in transfected CHO cells. However, rat CCK-58 was more potent than CCK-8 for stimulation of pancreatic protein secretion in the anesthetized rat. In addition, CCK-58 but not CCK-8 stimulated fluid secretion in this anesthetized rat model. These data suggest that regions outside the COOH terminus of rat CCK-58 influence the expression of CCK biological activity. The presence of only CCK-58 in the circulation and the fact that its biological activity differs from CCK-8 suggests that CCK-58 deserves scrutiny in other physiological models of CCK activity. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Res Serv 151, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Pasarow Mass Spectrometry Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90095 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. RP Reeve, JR (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Res Serv 151, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jreeve@ucla.edu FU NIDDK NIH HHS [DK-41301, R01-DK-33850] NR 39 TC 23 Z9 23 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2004 VL 286 IS 3 BP G395 EP G402 DI 10.1152/ajpgi.00020.2003 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 771KD UT WOS:000188783400005 PM 14604858 ER PT J AU Ichinose, F Bloch, KD Wu, JC Hataishi, R Aretz, HT Picard, MH Scherrer-Crosbie, M AF Ichinose, F Bloch, KD Wu, JC Hataishi, R Aretz, HT Picard, MH Scherrer-Crosbie, M TI Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart failure; remodeling ID NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR MASS; NATRIURETIC PEPTIDE RECEPTOR; CARDIAC-HYPERTROPHY; MYOCARDIAL-INFARCTION; ANGIOTENSIN-II; ESSENTIAL-HYPERTENSION; HEART-FAILURE; SUDDEN-DEATH; IN-VIVO AB To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3(-/-) mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3(-/-) than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3-/- than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3(-/-) than in WT mice at 28 days after TAC. Mortality was greater in NOS3(-/-) than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3(-/-) mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM ichinose@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [HL-42397, HL-57172, HL-70896] NR 26 TC 81 Z9 83 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2004 VL 286 IS 3 BP H1070 EP H1075 DI 10.1152/ajpheart.00940.2003 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 771KB UT WOS:000188783200034 PM 14644766 ER PT J AU Tan, Y Hutchison, FN Jaffa, AA AF Tan, Y Hutchison, FN Jaffa, AA TI Mechanisms of angiotensin II-induced expression of B-2 kinin receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE AT(1) receptors; mitogen-activated protein kinase; vascular smooth muscle cells ID VASCULAR SMOOTH-MUSCLE; ACTIVATED PROTEIN-KINASE; RENIN GENE-EXPRESSION; C-FOS INDUCTION; PROSTAGLANDIN E(2); CONVERTING-ENZYME; RENAL KALLIKREIN; TYPE-2 RECEPTOR; NITRIC-OXIDE; BRADYKININ AB Although the primary roles of the kallikrein-kinin system and the renin-angiotensin system are quite divergent, they are often intertwined under pathophysiological conditions. We examined the effect of ANG II on regulation of B-2 kinin receptors (B2KR) in vascular cells. Vascular smooth muscle cells (VSMC) were treated with ANG II in a concentration (10(-9)-10(-6) M)-and time (0-24 h)-dependent manner, and B2KR protein and mRNA levels were measured by Western blots and PCR, respectively. A threefold increase in B2KR protein levels was observed as early as 6 h, with a peak response at 10(-7) M. ANG II (10(-7) M) also increased B2KR mRNA levels twofold 4 h after stimulation. Actinomycin D suppressed the increase in B2KR mRNA and protein levels induced by ANG II. To elucidate the receptor subtype involved in mediating this regulation, VSMC were pretreated with losartan (AT(1) receptor antagonist) and/or PD-123319 (AT(2) receptor antagonist) at 10 muM for 30 min, followed by ANG II (10(-7) M) stimulation. Losartan completely blocked the ANG II-induced B2KR increase, whereas PD-123319 had no effect. In addition, expression of B2KR mRNA levels was decreased in AT(1A) receptor knockout mice. Finally, to determine whether ANG II stimulates B2KR expression via activation of the MAPK pathway, VSMC were pretreated with an inhibitor of p42/p44(mapk) (PD-98059) and/or an inhibitor of p38(mapk) (SB-202190), followed by ANG II (10(-7) M) for 24 h. Selective inhibition of the p42/p44(mapk) pathway significantly blocked the ANG II-induced increase in B2KR expression. These findings demonstrate that ANG II regulates expression of B2KR in VSMC and provide a rationale for studying the interaction between ANG II and bradykinin in the pathogenesis of vascular dysfunction. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Jaffa, AA (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet Med Genet, 114 Doughty St,POB 250776, Charleston, SC 29425 USA. EM jaffaa@musc.edu FU NHLBI NIH HHS [HL-55782, HL-71255]; NIDDK NIH HHS [DK-46543] NR 48 TC 28 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2004 VL 286 IS 3 BP H926 EP H932 DI 10.1152/ajpheart.00757.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 771KB UT WOS:000188783200016 PM 14766673 ER PT J AU Ichimura, T Hung, CC Yang, SA Stevens, JL Bonventre, JV AF Ichimura, T Hung, CC Yang, SA Stevens, JL Bonventre, JV TI Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cisplatin; S-(1,1,2,2-tetrafluoroethyl)-L-cysteine; folic acid; acute renal failure; kidney toxicity ID RAT-KIDNEY; REPERFUSION INJURY; EPITHELIAL-CELLS; GENE-EXPRESSION; C-FOS; PROTEIN; GROWTH; HYPERTROPHY; ADHESION; ISCHEMIA AB Nephrotoxicity is a common side effect of therapeutic interventions, environmental insults, and exposure to toxicants in the workplace. Although biomarkers for nephrotoxicity are available, they often lack sensitivity and are not specific as indicators of epithelial cell injury. Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein with extracellular immunoglobulin and mucin domains. The mRNA and protein for Kim-1 are expressed at very low levels in normal rodent kidney, but expression increases dramatically after injury in proximal tubule epithelial cells in postischemic rodent kidney and in humans during ischemic acute renal failure. To evaluate the utility of Kim-1 as a biomarker for other types of renal injury, we analyzed tissue and urinary expression in response to three different types of nephrotoxicants in the rat: S-(1,1,2,2-tetrafluoroethyl)-L-cysteine ( TFEC), folic acid, and cisplatin. Marked increases in Kim-1 expression were confirmed by immunoblotting in all three models. The protein was shown to be localized to the proximal tubule epithelial cell by immunofluorescence. Furthermore, Kim-1 protein was detected in urine of toxicant-treated rats. The temporal pattern of expression in response to TFEC is similar to the Kim-1 expression pattern in the postischemic kidney. In folic acid-treated kidneys, Kim-1 is clearly localized to the apical brush border of the well-differentiated proximal tubular epithelial cells. After folic acid treatment, expression of Kim-1 is present in the urine despite no significant increase in serum creatinine. Cisplatin treatment results in early detection of urinary Kim-1 protein and diffuse Kim-1 expression in S3 cells of the proximal tubule. Kim-1 can be detected in the tissue and urine on days 1 and 2 after cisplatin administration, occurring before an increase in serum creatinine. The upregulation of expression of Kim-1 and its presence in the urine in response to exposure to various types of nephrotoxicants suggest that this protein may serve as a general biomarker for tubular injury and repair processes. C1 Brigham & Womens Hosp, Med Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Lilly Res Labs, Greenfield, IN 46140 USA. RP Ichimura, T (reprint author), Harvard Inst Med, Div Renal, 4 Blackfan Circle,5th Floor,Rm 550, Boston, MA 02115 USA. EM tichimura@partners.org FU NIDDK NIH HHS [DK-38453, DK-39773, DK-46267]; NINDS NIH HHS [NS-10828] NR 42 TC 309 Z9 330 U1 3 U2 17 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 MAR 1 PY 2004 VL 286 IS 3 BP F552 EP F563 DI 10.1152/ajprenal.00285.2002 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 770DG UT WOS:000188707500016 PM 14600030 ER PT J AU Hirshfeld-Becker, DR Biederman, J Faraone, SV Segool, N Buchwald, J Rosenbaum, JF AF Hirshfeld-Becker, DR Biederman, J Faraone, SV Segool, N Buchwald, J Rosenbaum, JF TI Lack of association between behavioral inhibition and psychosocial adversity factors in children at risk for anxiety disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MACARTHUR LONGITUDINAL TWIN; PSYCHIATRIC-DISORDERS; PANIC DISORDER; FOLLOW-UP; SOCIAL ANXIETY; CHILDHOOD; PSYCHOPATHOLOGY; ADOLESCENT; PARENTS AB Objective: In a previous controlled study of offspring at risk for anxiety disorders, the authors found that parental panic disorder with comorbid major depression was associated with child behavioral inhibition, the temperamental tendency to be quiet and restrained in unfamiliar situations. To explore whether this association was mediated by environmental factors, the authors examined associations between psychosocial adversity variables and behavioral inhibition in this group of children. Method: Subjects included 200 offspring of parents with panic disorder and/or major depression and 84 comparison children of parents without mood or anxiety disorders. Behavioral inhibition was assessed through laboratory observations. The associations between behavioral inhibition and the following psychosocial factors were examined: socioeconomic status; an index of adversity factors found in previous studies to be additively associated with child psychopathology; family intactness, conflict, expressiveness, and cohesiveness; exposure to parental psychopathology; sibship size; birth order; and gender. Results: The results showed no associations between behavioral inhibition and any of the psychosocial factors in the study group as a whole, despite adequate power to detect medium effect sizes. Among low-risk comparison children only, SOME, definitions of behavioral inhibition were associated with low socioeconomic status, low family cohesion, and female gender. Conclusions: The results suggest that the psychosocial adversity factors examined in this study do not explain the previous finding that offspring of parents with panic disorder are at high risk for behavioral inhibition. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Clin Psychopharmacol Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Cambridge, MA 02138 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-01538-02, MH-47077-05] NR 50 TC 15 Z9 18 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, 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 MAR PY 2004 VL 161 IS 3 BP 547 EP 555 DI 10.1176/appi.ajp.161.3.547 PG 9 WC Psychiatry SC Psychiatry GA 818WU UT WOS:000221276000022 PM 14992982 ER PT J AU Keane, MM Wong, BM Verfaellie, M AF Keane, MM Wong, BM Verfaellie, M TI Do priming effects in perceptual identification and word judgment reflect different underlying mechanisms? SO AMERICAN JOURNAL OF PSYCHOLOGY LA English DT Article ID IMPLICIT MEMORY; SUBLEXICAL COMPONENTS; PSEUDOWORDS; NONWORDS; AMNESIA; ACTIVATION AB We examined priming of orthographically illegal nonwords in a perceptual identification task and a word judgment task in undergraduate participants. In perceptual identification, priming was significant and equivalent after structural or phonological encoding. In word judgment, priming was significant after phonological encoding but not structural encoding. In a follow-up experiment in older control participants and amnesic participants, priming in word judgment was not significant. Older control participants found the stimuli more difficult to pronounce than did undergraduate participants, and word judgment priming in undergraduate participants was significant only for the stimuli that were judged easy to pronounce. These findings demonstrate that priming in perceptual identification and word judgment extends to novel stimuli that are not linked to preexisting lexical or sublexical representations but that priming occurs at different levels in the two tasks: at a featural or orthographic level in perceptual identification and at a phonological level in word judgment. C1 Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA USA. RP Keane, MM (reprint author), Wellesley Coll, Dept Psychol, Wellesley, MA 02481 USA. EM mkeane@wellesley.edu FU PHS HHS [26985, 57681] NR 33 TC 4 Z9 4 U1 0 U2 4 PU UNIV ILLINOIS PRESS PI CHAMPAIGN PA 1325 S OAK ST, CHAMPAIGN, IL 61820-6903 USA SN 0002-9556 J9 AM J PSYCHOL JI Am. J. Psychol. PD SPR PY 2004 VL 117 IS 1 BP 93 EP 113 DI 10.2307/1423598 PG 21 WC Psychology, Multidisciplinary SC Psychology GA 801CH UT WOS:000220073500006 PM 15058859 ER PT J AU Abbara, S Migrino, RQ Sosnovik, DE Leichter, JA Brady, TJ Holmvang, G AF Abbara, S Migrino, RQ Sosnovik, DE Leichter, JA Brady, TJ Holmvang, G TI Value of fat suppression in the MRI evaluation of suspected arrhythmogenic right ventricular dysplasia SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DIAGNOSIS; CARDIOMYOPATHY AB OBJECTIVE. Arrhythmogenic right ventricular dysplasia (ARVD) is characterized by intramyocardial fibrofatty change. Fat suppression performed during conventional spin-echo imaging has been used to confirm fatty infiltration. The utility of fat suppression for enhancing the interpretation of studies of suspected ARVD has not previously been formally tested. We investigated the value of fat suppression for enhancing the interpretation of intramyocardial fatty infiltration. MATERIALS AND METHODS. Twenty-six consecutive patients clinically referred for evaluation of possible ARVD underwent cardiac MRI. Two independent observers reviewed the images retrospectively. Intramyocardial areas (n = 401) that had increased signal intensity relative to normal surrounding myocardium on T1-weighted conventional spin-echo images ("index areas") were identified. The index areas were interpreted for presence of fatty infiltration using two sets of images: The first set was obtained without fat suppression, and the second set was obtained with fat suppression. Agreement between reviewers and confidence of interpretation were determined and compared. RESULTS. Interobserver agreement was measured using a 5-point scale: 1, definitely not fat; 2, probably not fat; 3, equivocal; 4, probably fat; and 5, definitely fat. The resulting kappa values were 0.35 for non-fat-suppressed images and 0.55 for fat-suppressed images. Interobserver kappa increased from 0.67 without fat suppression to 0.90 with fat suppression using a 3-point scale: 1, not fat; 2, equivocal; and 3, fat. Confidence in the diagnosis increased from 7.2 without fat suppression to 8.8 with fat suppression (p < 0.0001) on a 10-point scale ranging from 1, not confident, to 10, very confident. CONCLUSION. The use of fat-suppressed in addition to non-fat-suppressed conventional T1-weighted spin-echo imaging increased interobserver agreement and confidence in diagnosis and evaluation of intramyocardial fatty infiltration in patients who were suspected to have ARVD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Ste 400, Boston, MA 02114 USA. EM sabbara@partners.org NR 13 TC 10 Z9 10 U1 0 U2 2 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 MAR PY 2004 VL 182 IS 3 BP 587 EP 591 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 776PV UT WOS:000189126100009 PM 14975951 ER PT J AU Stadler, A Schima, W Prager, G Homolka, P Heinz, G Saini, S Eisenhuber, E Niederle, B AF Stadler, A Schima, W Prager, G Homolka, P Heinz, G Saini, S Eisenhuber, E Niederle, B TI CT density measurements for characterization of adrenal tumors ex vivo: Variability among three CT scanners SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; ATTENUATION VALUES; ENHANCED CT; MASSES; ADENOMAS; DIFFERENTIATION; NONADENOMAS; NUMBERS; GLAND; COEFFICIENTS AB OBJECTIVE. Many studies have suggested that Hounsfield measurements on unenhanced CT can reliably differentiate adrenal adenomas from nonadenomas using a scanner-independent threshold level. The purpose of this study was to determine whether establishment of a scanner-independent threshold for differentiation of adenomas from nonadenomas is technically feasible. MATERIALS AND METHODS. Surgically resected adrenal tumor specimens (total, seven; adenomas, three; nonadenomas, four; size range, 17-76 mm), were placed in an anthropomorphic phantom. Lesion specimens were scanned with one MDCT and two single-detector scanners. Scanning protocols for all three scanners included variations in kilovoltage (140, 120, and 80 [Somatom Plus 4, Somatom VolumeZoom] or 100 [Tomoscan AV] kVp) and slice thickness. Hounsfield measurements were performed on exactly matched slices using regions of interest of a constant size. RESULTS. The difference in lesion Hounsfield measurements among scanning protocols with 140, 120, and 100/80 kVp was up to 6.2 H for the adenoma group and up to 3.8 H for the nonadenoma group. The comparison of the Tomoscan AV and the Somatom Plus 4 scanners showed a mean difference of 2.6 H at 120 kVp and of 4.6 H at 140 kVp. The differences between the Tomoscan AV and Somatom VolumeZoom scanners were 1.7 and 3.6 H for 120 and 140 kVp, respectively. Between the two Somatom scanners, the divergence was 2.9 and 3.3 H for the two kilovoltage settings. Differentiation between adenomas and nonadenomas was better at lower kilovoltage. Slice thickness did not affect the CT density measurements significantly. CONCLUSION. Significant differences in CT density measurements of adrenal tumors may occur when different CT scanners or imaging protocols are used. The dependence of measurements on scanner type and scanning technique makes the recommendation of a universal, scanner- and protocol-independent threshold problematic. C1 Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. Univ Vienna, Dept Surg, Vienna, Austria. Univ Vienna, Dept Biomed Engn & Phys, Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schima, W (reprint author), Univ Vienna, Dept Radiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM wolfgang.schima@univie.ac.at RI Homolka, Peter/I-2168-2012 OI Homolka, Peter/0000-0002-2300-3015 NR 27 TC 24 Z9 24 U1 0 U2 2 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 MAR PY 2004 VL 182 IS 3 BP 671 EP 675 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 776PV UT WOS:000189126100024 PM 14975968 ER PT J AU Kassarjian, A Zurakowski, D Dubois, J Paltiel, HJ Fishman, SJ Burrows, PE AF Kassarjian, A Zurakowski, D Dubois, J Paltiel, HJ Fishman, SJ Burrows, PE TI Infantile hepatic hemangiomas: Clinical and imaging findings and their correlation with therapy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTERFERON ALPHA-2A TREATMENT; VASCULAR ANOMALIES; INFANCY; HEMANGIOENDOTHELIOMAS; EXPERIENCE AB OBJECTIVE. This study was undertaken to determine different imaging patterns in infantile hepatic hemangiomas and to explore the relationship between clinical presentations, imaging findings, and response to therapy. MATERIALS AND METHODS. The imaging studies and clinical records of all patients. l with infantile hepatic hemangiomas from two tertiary children's hospitals were reviewed.,. Univariate and multivariate stepwise logistic regression techniques were used to determine. whether clinical presentation and imaging variables differentiated the type of treatment required. RESULTS. Typical hemangiomas appeared as focal or multifocal T2-hyperintense spheres with centripetal contrast enhancement and dilated feeding and draining vessels. Three atypical patterns included focal mass lesions with central varix with or without direct shunts, focal mass with central necrosis or thrombosis, and massive hemangiomatous involvement of the liver with abdominal vascular compression. In general, patients with focal lesions without high flow needed no treatment, and those with central varix and direct shunts developed severe high-output cardiac failure that responded quickly to embolization. The pattern of massive replacement of liver was associated with hypothyroidism, abdominal compartment syndrome, and a high mortality rate. Multivariate analysis of 55 patients indicated that congestive heart failure was the only independent predictor of treatment (p = 0.005). The presence of a shunt was the only independent factor associated with embolization or surgery (p = 0.002). CONCLUSION. Although the imaging features of infantile hepatic hemangiomas vary to some extent, MRI features are typical in most patients and certain imaging findings are predictive of the clinical course. MRI is the technique of choice in diagnosing infantile hepatic masses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Musculoskeletal Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA USA. Univ Montreal, Hop St Justine, Dept Biostat, Montreal, PQ H3T 1C5, Canada. RP Kassarjian, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Musculoskeletal Radiol, 15 Parkman St,Ste 515, Boston, MA 02114 USA. NR 18 TC 72 Z9 74 U1 0 U2 0 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 MAR PY 2004 VL 182 IS 3 BP 785 EP 795 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 776PV UT WOS:000189126100042 PM 14975986 ER PT J AU Mair, SD Isbell, WM Gilo, TJ Schlegel, TF Hawkins, RJ AF Mair, SD Isbell, WM Gilo, TJ Schlegel, TF Hawkins, RJ TI Triceps tendon ruptures in professional football players SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE triceps; tendon; rupture; football; elbow ID AVULSION AB Background: Distal rupture of the triceps tendon is a rare injury, and treatment guidelines are not well established. Hypothesis: Football players with triceps tendon ruptures will be able to return to their sport with minimal functional deficits. Study Design: Uncontrolled retrospective review. Methods: Twenty-one partial and complete ruptures of the triceps tendon were identified in 19 National Football League players over a period of 6 years. Team physicians retrospectively reviewed training room, clinical, and operative notes for each of these players. Results: Most of the injured players were linemen. The most common mechanism of injury was an eccentric load to a contracting triceps. Seven players had prodromal symptoms prior to injury, and 5 had received a cortisone injection. Eleven elbows with complete tears underwent surgical repair. Of 10 players with partial tears, 6 healed without surgery. One player suffered a subsequent complete tear requiring surgery, and 3 with residual pain and weakness underwent surgical repair following the season. Two surgical complications occurred, both requiring a second operation. All of the players but 1 returned to play at least one season of professional football after their injury. Conclusions: Partial triceps tendon ruptures can heal without functional deficit. Surgical repair for complete ruptures generally produces good functional results and allows return to play. C1 Univ Kentucky, Lexington, KY 40536 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Steadman Hawkins Clin, Denver, CO USA. Steadman Hawkins Clin, Vail, CO USA. RP Mair, SD (reprint author), Univ Kentucky, 740 S Limestone,K-401 Kentucky Clin, Lexington, KY 40536 USA. NR 18 TC 41 Z9 43 U1 0 U2 6 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAR PY 2004 VL 32 IS 2 BP 431 EP 434 DI 10.1177/0095399703258707 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 776HG UT WOS:000189110100020 PM 14977669 ER PT J AU O'Connell, JB Maggard, MA Livingston, EH Yo, CK AF O'Connell, JB Maggard, MA Livingston, EH Yo, CK TI Colorectal cancer in the young SO AMERICAN JOURNAL OF SURGERY LA English DT Review DE cancer; colorectal; review; risk factors; young ID 40 YEARS OLD; PATIENTS LESS; LARGE BOWEL; 3 DECADES; CARCINOMA; AGE; COLON; RECTUM; ADENOCARCINOMA; ADULTS AB Background: Colorectal cancer (CRC) is generally thought of as a disease of older persons; however a significant proportion of patients <40 years present with this disease. Many investigators have published single-institution series on CRC in the young, yet the data vary markedly. We performed a structured review of the current literature aiming to (1) characterize CRC in the young population and (2) determine how CRC in this population should be further addressed regarding detection and treatment. Data sources: A Medline literature search was completed. Articles were chosen to include those studies that examined patients <40 years old. A total of 55 articles were chosen from the search and review of the bibliographies. Conclusions: We found that CRC in the young population appears to be more aggressive, to present with later stage, and to have poorer pathologic findings. However, if detected early, young patients with Dukes' stage A or B lesions have better overall 5-year survival rates. These findings emphasize the need for health care providers to have a heightened awareness when caring for this young population, particularly because excellent modalities exist to diagnose and treat colorectal cancer. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Encino, CA 91436 USA. W Los Angeles Vet Affairs Hosp, Dept Surg, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 5001 Gloria Ave, Encino, CA 91436 USA. EM jbocjboc@hotmail.com NR 60 TC 96 Z9 101 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2004 VL 187 IS 3 BP 343 EP 348 DI 10.1016/j.amjsurg.2003.12.020 PG 6 WC Surgery SC Surgery GA 801PL UT WOS:000220107700006 PM 15006562 ER PT J AU Hollingsworth, AB Singletary, SE Morrow, M Francescatti, DS O'Shaughnessy, JA Hartman, AR Haddad, B Schnabel, FR Vogel, VG AF Hollingsworth, AB Singletary, SE Morrow, M Francescatti, DS O'Shaughnessy, JA Hartman, AR Haddad, B Schnabel, FR Vogel, VG TI Current comprehensive assessment and management of women at increased risk for breast cancer SO AMERICAN JOURNAL OF SURGERY LA English DT Review DE breast cancer; risk assessment; ductal lavage; hormone replacement therapy; risk management strategy; chemoprevention; magnetic resonance imaging ID HORMONE REPLACEMENT THERAPY; SURGICAL-ADJUVANT-BREAST; ESTROGEN PLUS PROGESTIN; BILATERAL PROPHYLACTIC MASTECTOMY; RANDOMIZED CONTROLLED-TRIAL; BOWEL-PROJECT P-1; FAMILY-HISTORY; OVARIAN-CANCER; POSTMENOPAUSAL WOMEN; DUCTAL LAVAGE AB The potential for reducing the risk of breast cancer through selective estrogen receptor modulators, aromatase inhibitors, and surgery has generated interest in the use of quantitative models of risk assessment. With the addition of ductal lavage cytology to traditional epidemiologic risk factors, a discovery of cellular atypia can result in refinement of assigned risk values, while simultaneously optimizing patient selection for selective estrogen receptor modulators utilization. In view of increasing complexity in this arena, a Risk Assessment Working Group was formed to outline management strategies for the patient at an elevated risk for the development of breast cancer. No longer a statistical exercise, quantitative risk assessment is part of basic breast care and comprehensive management includes a discussion of the following: ductal lavage for improved risk stratification, multiple options for risk reduction, and high risk surveillance strategies that might incorporate investigational imaging protocols. (C) 2004 Excerpta Medica, Inc. All rights reserved. C1 Mercy Hlth Ctr, Dept Surg, Mercy Womens Ctr, Oklahoma City, OK 73120 USA. MD Anderson Canc Ctr, Dept Surg, Houston, TX USA. Northwestern Univ, Sch Med, Dept Surg, Chicago, IL 60611 USA. Rush Med Coll, Dept Surg, Chicago, IL 60612 USA. US Oncol, Baylor Sammons Canc Ctr, Dallas, TX USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Susan G Komen Fdn, Dallas, TX USA. Columbia Presbyterian Med Ctr, Dept Surg, New York, NY USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Hollingsworth, AB (reprint author), Mercy Hlth Ctr, Dept Surg, Mercy Womens Ctr, 4300 McAuley Blvd, Oklahoma City, OK 73120 USA. EM ahollingsworth@ok.mercy.net OI Schnabel, Freya/0000-0002-6393-7453 NR 83 TC 24 Z9 27 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2004 VL 187 IS 3 BP 349 EP 362 DI 10.1016/j.amjsurg.2003.12.025 PG 14 WC Surgery SC Surgery GA 801PL UT WOS:000220107700007 PM 15006563 ER PT J AU Parker, RL Dadmanesh, F Young, RH Clement, PB AF Parker, RL Dadmanesh, F Young, RH Clement, PB TI Polypoid endometriosis - A clinicopathologic analysis of 24 cases and a review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometriosis; polypoid endometriosis; estrogen; adenosarcoma ID OVARIAN ENDOMETRIOSIS; EPITHELIAL METAPLASIAS; ATYPICAL ENDOMETRIOSIS; LONG-TERM; HYPERPLASIA; COLON; ASSOCIATION; SARCOMA; TUMORS; WOMEN AB We describe 24 cases of polypoid endometriosis, most of which were referred because of problems in differential diagnosis, particularly distinction from a low-grade mullerian neoplasm. The patients were 23 to 78 years (mean 52.5 years) of age. Seven patients were on unopposed estrogen, four on combined estrogen-progestin therapy, and one patient had a synchronous ovarian thecoma. The most common clinical presentations were a pelvic mass, vaginal polypoid masses, and large bowel obstruction. In some cases, the intra-operative findings suggested a neoplasm. Sites of involvement in order of frequency included colon, ovary, uterine serosa, cervical and/or vaginal mucosa, ureter, fallopian tube, omentum, bladder, paraurethral and paravaginal soft tissue, and retroperitoneum. Multiple sites were involved in seven cases. Five cases occurred within ovarian or extraovarian endometriotic cysts. The lesions ranged up to 14 cm in size and formed polypoid, pink, gray or tan, masses. On microscopic examination, the polypoid masses were composed of an admixture of endometriotic glands and stroma. A variety of glandular architectural patterns were observed, sometimes in combination, most commonly cystic and noncystic simple hyperplasia, but also simple or complex hyperplasia with atypia, disordered proliferative, and cystic atrophy. Various types of epithelial metaplasia (tubal, mucinous, squamous, papillary syncytial metaplasia) were common. Hemorrhage, fibrosis, prominent thick-walled blood vessels, hemosiderin-laden histiocytes, and decidual change were also present in some cases. Eighteen cases were associated with usual (nonpolypoid) endometriosis. In one case, polypoid endometriosis merged with a mucinous borderline tumor of endocervical-type. In all but two cases, polypoid endometriosis lacked periglandular stromal hypercellularity, stromal atypia, and intraglandular stromal papillae, helping distinguish it from adenosarcoma. Focal intraglandular stromal papillae were noted in two cases with focal mild periglandular stromal hypercellularity in one of them, but no stromal atypia was present in either case. Follow-up data in 17 patients indicated that 15 patients were alive without evidence of residual disease, I was alive with residual endometriosis, and I died of other causes. In conclusion, polypoid endometriosis is a rare manifestation of endometriosis that may be mistaken for a neoplasm on clinical, intraoperative, or pathologic assessment. Some cases may be attributable to exogenous hormones or hyperestrinism and, like conventional endometriosis, some may evolve into a premalignant or, rarely, a neoplastic lesion. The main lesion in the differential is a mullerian (mesodermal) adenosarcoma. C1 Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada. Calgary Lab Serv, Calgary, AB, Canada. Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Parker, RL (reprint author), Foothills Prov Gen Hosp, Dept Pathol & Lab Med, 1403-29 St NW, Calgary, AB T2N 2T9, Canada. EM rlparker@interchange.ubc.ca NR 31 TC 55 Z9 60 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2004 VL 28 IS 3 BP 285 EP 297 DI 10.1097/00000478-200403000-00001 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 779TH UT WOS:000189316500001 PM 15104291 ER PT J AU Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Tseng, YL Houser, S Mueller, N Prabharasuth, D Alt, A Moran, K Cheng, J Behdad, A Sachs, DH Fishman, JA Schuurman, HJ Awwad, M Cooper, DKC AF Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Tseng, YL Houser, S Mueller, N Prabharasuth, D Alt, A Moran, K Cheng, J Behdad, A Sachs, DH Fishman, JA Schuurman, HJ Awwad, M Cooper, DKC TI Suppression of natural and elicited antibodies in pig-to-baboon heart transplantation using a human anti-human CD154 mAb-based regimen SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Anti-CD154 monoclonal antibody; antiGal antibody; baboon; costimulatory blockade; heart transplantation; pig; xenotransplantation ID HEMATOPOIETIC-CELL TRANSPLANTATION; ACUTE VASCULAR REJECTION; XENOGRAFT REJECTION; ORGAN XENOTRANSPLANTATION; KIDNEY-TRANSPLANTATION; NONHUMAN PRIMATE; GAL ANTIBODIES; PORCINE KIDNEY; COAGULATION; DEPLETION AB Natural and elicited antipig antibodies (Abs) lead to acute humoral xenograft rejection (AHXR). Ten baboons underwent heterotopic heart transplantation (Tx) from human decay-accelerating factor (hDAF) pigs. Depletion of anti-Galalpha1, 3Gal (Gal) Abs was achieved by the infusion of a Gal glycoconjugate from day - 1. Immunosuppression included induction of antithymocyte globulin, thymic irradiation, and cobra venom factor, and maintenance with a human antihuman CD154 mAb, mycophenolate mofetil, and methylprednisolone; heparin and prophylactic ganciclovir were also administered. Pig heart survival ranged from 4 to 139 (mean 37, median 27) days, with three functioning for > 50 days. Graft failure (n = 8) was from classical AHXR [4], thrombotic microangiopathy [3], or intragraft thrombosis [1], with death (n = = 2) from pneumonia [1], or possible drug toxicity (with features of thrombotic microangiopathy) [1]. Anti-Gal Abs (in mug/mL) were depleted by Gal glycoconjugate before graft implantation from means of 41.3 to 6.3 (IgM) and 12.4-4.6 (IgG), respectively, and at graft excision were 6.3 and 1.7 mug/mL, respectively. No elicited Abs developed, and no cellular infiltration was seen. The treatment regimen was effective in maintaining low anti-Gal Ab levels and in delaying or preventing AHXR. The combination of costimulatory blockade and heparin with Tx of a Gal-negative pig organ may prolong graft survival further. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. Immerge BioTherapeut Inc, Charlestown, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM David.Cooper@tbrc.mgh.harvard.edu RI Dor, Frank/E-1032-2013; Mueller, Nicolas/B-6864-2013 OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191 FU NIAID NIH HHS [1P01 AI 45897, 5T32 AI 07529-04] NR 37 TC 95 Z9 96 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2004 VL 4 IS 3 BP 363 EP 372 DI 10.1111/j.1600-6143.2004.00353.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 774MY UT WOS:000188988100010 PM 14961988 ER PT J AU Trail, M Nelson, ND Van, JN Appel, SH Lai, EC AF Trail, M Nelson, ND Van, JN Appel, SH Lai, EC TI Major stressors facing patients with amyotrophic lateral sclerosis (ALS): a survey to identify their concerns and to compare with those of their caregivers SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article DE amyotrophic lateral sclerosis; stressors; quality of life; caregivers; existential; physical; psychosocial ID QUALITY-OF-LIFE; DISEASE AB OBJECTIVE: To identify and compare the primary existential, physical, and psychosocial stressors affecting patients with ALS and their caregivers. Health care providers, together with patients and their caregivers, are challenged to identify both physical and psychosocial concerns that have the greatest impact on quality of life over the course of a serious illness. It is also helpful to understand the priorities of these concerns from the patients' and caregivers' perspectives so that we can render optimal care and help patients and their families with the myriad problems that accompany a progressive and fatal disease. METHODS: We analyzed responses from the first 66 patients with ALS and 61 ALS caregivers who attended the Baylor College of Medicine, Department of Neurology, Vicki Appel MDA ALS Clinic and who completed our internally generated 19-item survey. Subjects were asked to choose their three most important concerns. For analysis purposes we categorized the data into three domains: existential, physical, and psychosocial. Demographic data were collected. The Appel ALS Rating Scale (AALS) was used to measure disease symptom severity. RESULTS: Sixty-six patients (45 men, 21 women) with a mean age of 57.9 (range 30-82) years and 61 caregivers completed the checklist. At the time the patients completed the survey, their mean AALS total score was 77.0 (range 34-132), indicating mild to moderate disability. The most important stressors identified by patients and caregivers were existential concerns (86.4% of patients and 79.7% of caregivers) and physical stressors (80.3% of patients and 76.3% of caregivers). Less than 50% of both groups endorsed psychosocial stressors (38%). However, when we analyzed the domain specific items, there was a significant difference between patients and caregivers on worries about the patient's dependency (37.9% of patients and 6.8% of caregivers). DISCUSSION: Health care professionals should apply a holistic approach to treatment and care of patients with ALS. Families should be included in the process, and it should not be assumed that patients and caregivers will agree on all issues. Future research should focus on therapeutic interventions to help ALS patients and their families cope with the multiple stressors accompanying a catastrophic illness. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Lai, EC (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. EM elai@bcm.tmc.edu NR 18 TC 22 Z9 22 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD MAR PY 2004 VL 5 IS 1 BP 40 EP 45 DI 10.1080/14660820310016075 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 807QS UT WOS:000220516600008 PM 15204023 ER PT J AU Raber, J Fan, Y Matsumori, Y Liu, ZY Weinstein, PR Fike, JR Liu, JL AF Raber, J Fan, Y Matsumori, Y Liu, ZY Weinstein, PR Fike, JR Liu, JL TI Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSIENT GLOBAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-ISCHEMIA; BRAIN IRRADIATION; MOTOR RECOVERY; DENTATE GYRUS; X-IRRADIATION; ADULT BRAIN; STROKE; RAT AB Increased neurogenesis after cerebral ischemia suggests that functional recovery after stroke may be attributed, in part, to neural regeneration. In this study, we investigated the role of neurogenesis in the behavioral performance of gerbils after cerebral global ischemia. We used ionizing radiation to decrease neural regeneration, and 2 weeks later cerebral global ischemia was induced by bilateral common carotid artery occlusion. One month after the occlusion, the animals were behaviorally tested. Irradiation alone reduced neurogenesis but did not change vascular or dendritic morphology at the time of behavioral testing. Neither did irradiation, ischemia, or combined treatment impair rotor-rod performance or alter open-field activity. Gerbils subjected to both irradiation and ischemia demonstrated impaired performance in the water-maze task, compared with those that received only ischemia, radiation, or no treatment. These impairments after cerebral global ischemia under conditions of reduced neurogenesis support a role for the production of new cells in mediating functional recovery. C1 Univ Calif San Francisco, Dept Neurol Surg 112C, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR USA. RP Liu, JL (reprint author), Univ Calif San Francisco, Dept Neurol Surg 112C, 4150 Clement St, San Francisco, CA 94121 USA. EM miro@itsa.ucsf.edu RI Liu, Jialing/A-8627-2012 OI Liu, Jialing/0000-0003-4420-4382 FU NCI NIH HHS [R01 CA 76141]; NIA NIH HHS [R01 AG 20079]; NINDS NIH HHS [R21 NS 40088, R01 NS 40469] NR 44 TC 160 Z9 166 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2004 VL 55 IS 3 BP 381 EP 389 DI 10.1002/ana.10853 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 779BM UT WOS:000189275800010 PM 14991816 ER PT J AU Hodges, SH Anderson, AL Connor, NP AF Hodges, SH Anderson, AL Connor, NP TI Remodeling of neuromuscular junctions in aged rat genioglossus muscle SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Broncho-Esophagological-Association CY MAY 02-03, 2003 CL NASHVILLE, TN SP Amer Broncho Esophagol Assoc DE aging; confocal microscopy; genioglossus muscle; neuromuscular junction ID CONTRACTILE PROPERTIES; DIFFERENTIAL CHANGES; MOTOR UNITS; NERVE; TONGUE; REGENERATION; ASPIRATION; PHARYNGEAL; DYSPHAGIA; ANIMALS AB Speech and swallowing disorders represent a large clinical problem in elderly persons. Poor lingual control is associated with both speech and swallowing impairment. Studies of limb and laryngeal muscles suggest that age-related musculoskeletal changes may be characterized by remodeling of muscles, nerves, and their connections at neuromuscular junctions (NMJs). To evaluate dynamic remodeling of NMJ structure in the tongue as a function of aging, we studied tongues from 10 aged and 10 young rats. A fluorescent, triple-labeled, immunohistochemical technique was used with genioglossus (GG) muscle samples to allow confocal microscopic visualization of receptor clusters, nerve terminals, axons, and synaptic vesicles. Normal axon terminals and receptor clusters were easily identified in young rat GG muscles, whereas aging induced a significantly higher degree of receptor dispersal. These results suggest that NMJ remodeling is found in aged GG muscles and may underlie the progressive neuromuscular changes observed in the elderly. C1 Univ Wisconsin, Ctr Clin Sci, Div Otolaryngol Head & Neck Surg, Dept Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Connor, NP (reprint author), Univ Wisconsin, Ctr Clin Sci, Div Otolaryngol Head & Neck Surg, Dept Surg, Room K4-711,600 Highland Ave, Madison, WI 53792 USA. NR 34 TC 12 Z9 13 U1 1 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2004 VL 113 IS 3 BP 175 EP 179 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 803CQ UT WOS:000220209600001 PM 15053197 ER PT J AU Varvares, MA Montgomery, WW AF Varvares, MA Montgomery, WW TI Repair of chronic subglottic stenosis with autogenous thyroid cartilage SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cartilage grafting; chronic subglottic stenosis; laryngeal stenosis; laryngeal stent; T tube ID PRIMARY TRACHEAL ANASTOMOSIS; PARTIAL CRICOID RESECTION; LARYNGOTRACHEAL RECONSTRUCTION; AURICULAR CARTILAGE; MANAGEMENT; GRAFTS; LARYNGEAL; CHILDREN AB Chronic subglottic stenosis continues to be a difficult management problem. Conservative management with bougienage, laser therapy, mitomycin-C, and/or steroid injections frequently fails. Definitive resection of the subglottis with thyrotracheal anastomosis has increased in popularity, but carries significant operative risks and postoperative complications. In the past 9 years, we have used a modification of a technique to successfully widen the subglottis, which we previously published 20 years ago. By a laryngocrico-tracheofissure approach, the cricoid cartilage is split vertically, both anteriorly and posteriorly. Cartilage grafts, obtained from the upper thyroid laminae anteriorly, are inserted in these splits. The posterior graft is fixed in place with specially designed pins, which improves graft fixation by adding rigidity and shortens the procedure. The repair is held in place for 3 to 4 weeks with either a silicone T tube or a conforming laryngeal stent. The charts of 21 consecutive patients treated with open repair of chronic subglottic stenosis were reviewed. The overall decannulation rate was 95%. We conclude that autogenous grafting is a useful tool in the treatment of chronic subglottic stenosis. Posterior cartilage graft fixation with our pin technique offers a significant advantage over suture fixation by improving graft stability and decreasing operative time, and has a high rate of decannulation. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Varvares, MA (reprint author), St Louis Univ, Dept Otolaryngol, 3635 Vista Ave Grand Blvd,POB 15250, St Louis, MO 63110 USA. NR 19 TC 4 Z9 7 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAR PY 2004 VL 113 IS 3 BP 212 EP 217 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 803CQ UT WOS:000220209600008 PM 15053204 ER PT J AU Liu, JH Chen, PW Asch, SM Busuttil, RW Ko, CY AF Liu, JH Chen, PW Asch, SM Busuttil, RW Ko, CY TI Surgery for hepatocellular carcinoma: Does it improve survival? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE hepatocellular carcinoma; HCC; surgery; survival; outcomes; liver cancer ID UNITED-STATES; HEPATIC RESECTION; WESTERN CENTER; CIRRHOSIS; QUALITY; CANCER; PROGRAM; CARE AB Background: The incidence and mortality of hepatocellular carcinoma (HCC) are increasing in the United States. Whether surgery is associated with improved survival at the population level is relatively unknown. To address this question, we used a population-based cancer registry to compare survival outcomes between patients receiving and not receiving surgery with similar tumor sizes and health status. Methods: By using the Surveillance, Epidemiology, and End Results database, we identified HCC patients who had surgically resectable disease as defined by published expert guidelines. After excluding patients with contraindications to surgery, we performed both survival analysis and Cox regression to identify predictors of improved survival. Results: Of the 4008 patients diagnosed with HCC between 1988 and 1998, 417 were candidates for surgical resection. The mean age was 63.6 years; mean tumor size was 3.3 cm. The 5-year overall survival with surgery was 33% with a mean of 47.1 months; without surgery, the 5-year overall survival was 7% with a mean of 17.9 months (P <.001). In the multivariate Cox regression, surgery was significantly associated with improved survival (P <.001). Specifically, patients who received surgery had a 55% decreased rate of death compared with patients who did not have surgery, even after controlling for tumor size, age, sex, and race. Conclusions: This study shows that surgical therapy is associated with improved survival in patients with unifocal, nonmetastatic HCC tumors <5 cm. If this is confirmed in future studies, efforts should be made to ensure that appropriate patients with resectable HCC receive high-quality care, as well as the opportunity for potentially curative surgery. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Liu, JH (reprint author), 11301 W Olymp Blvd,648, Los Angeles, CA 90064 USA. EM jerome8@ucla.edu NR 22 TC 52 Z9 54 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2004 VL 11 IS 3 BP 298 EP 303 DI 10.1245/ASO.2004.03.042 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 780KX UT WOS:000189380800013 PM 14993025 ER PT J AU Guller, U Anstrom, KJ Holman, WL Allman, RM Sansom, M Peterson, ED AF Guller, U Anstrom, KJ Holman, WL Allman, RM Sansom, M Peterson, ED TI Outcomes of early extubation after bypass surgery in the elderly SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTENSIVE-CARE UNIT; MECHANICALLY VENTILATED PATIENTS; RANDOMIZED CONTROLLED TRIAL; FAST-TRACK RECOVERY; CARDIAC-SURGERY; GRAFT-SURGERY; TRACHEAL EXTUBATION; MYOCARDIAL-ISCHEMIA; COST; STAY AB Background. While early extubation after coronary artery bypass grafting (CABG) has been associated with resource savings, its effect on patient outcomes remains unclear. The goal of the present investigation was to evaluate whether early extubation can be performed safely in elderly CABG patients in community practice. Methods. We studied 6,446 CABG patients, aged 65 years and older, treated at 35 hospitals between 1995 and 1998. Patients were categorized based on their post-CABG extubation duration (early, < 6 hours; intermediate, 6 to < 12 hours; and late, 12 to 24 hours). We compared unadjusted and risk-adjusted mortality, reintubation rates, and post-CABG length of stay (pLOS). We also examined the association between patients' intubation time and outcomes among patients with similar propensity for early extubation and among high-risk patient subgroups. Results. The overall mean post-CABG intubation time was 9.8 (SD 5.7) hours with 29% of patients extubated within 6 hours. After adjusting for preoperative risk factors patients extubated in less than 6 hours had significantly shorter postoperative hospital stays than those with later extubation times. Patients extubated early also tended to have equal or better risk-adjusted mortality than those with intermediate (odds ratio: 1.69, p = 0.08) or long intubation times (odds ratio: 1.97, p = 0.02). These results were consistent among patients with similar preoperative propensity for early extubation and among important high-risk patient subgroups. There was no evidence for higher reintubation rates among elderly patients selected for early extubation. Conclusions. In community practice, early extubation after CABG can be achieved safely in selected elderly patients. This practice was associated with shorter hospital stays without adverse impact on postoperative outcomes. (C) 2004 by The Society of Thoracic Surgeons. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Outcomes Res & Assessment Grp, Durham, NC 27710 USA. Univ Basel Hosp, Dept Surg, Div Gen Surg, CH-4031 Basel, Switzerland. Univ Alabama, Sch Med, Dept Surg,Birmingham Atlanta VA,GRECC, Birmingham VA Med Ctr,Alabama Qual Assurance Fdn, Birmingham, AL 35294 USA. Univ Alabama, Ctr Aging, Birmingham, AL USA. RP Peterson, ED (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 17969, Durham, NC 27715 USA. EM peter016@mc.duke.edu NR 37 TC 23 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2004 VL 77 IS 3 BP 781 EP 788 DI 10.1016/athoracsur.2003.09.059 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 779TL UT WOS:000189317000006 PM 14992871 ER PT J AU Bharti, A Ma, PC Maulik, G Singh, R Khan, E Skarin, AT Salgia, R AF Bharti, A Ma, PC Maulik, G Singh, R Khan, E Skarin, AT Salgia, R TI Haptoglobin alpha-subunit and hepatocyte growth factor can potentially serve as serum tumor biomarkers in small cell lung cancer SO ANTICANCER RESEARCH LA English DT Article DE alpha-haptoglobin; hepatocyte growth factor; small cell lung cancer; serum tumor biomarkers; proteomics ID C-MET; CLINICAL-SIGNIFICANCE; OVARIAN-CANCER; BREAST-CANCER; RECEPTOR; EXPRESSION; PROTEOMICS; PROTEINS; SURVIVAL; DOMAINS AB Background: Small cell lung cancer (SCLC) frequently presents as metastatic disease. It would be useful to detect serum tumor biomarkers at an earlier stage in order to improve the overall survival. Materials and Methods: Serum samples from SCLC patients (6 limited disease, 7 extensive disease, 4 relapsed disease, 4 no evidence of disease post-treatment) and 5 normal controls were used to identify tumor biomarkers utilizing proteomics. Serum hepatocyte growth factor was also studied using standard ELISA. Results: Utilizing MALDI-TOF-Mass Spectrometry (MS) based protein identification techniques, a SCLC specific overexpressed protein was identified to be haptoglobin alpha-subunit, with its serum level correlating with the disease stage. The mean level of alpha-haptoglobin was increased in SCLC serum as compared to the normal controls. Serum HGF was also studied as potential tumor biomarker and was found to correlate with the disease status. Either serum alpha-haptoglobin relative level (above 1.9 U), or HGF level (above 500 pg/ml) was associated with a trend towards worse survival. Conclusion: Our current findings suggest that serum levels of alpha-haptoglobin and HGF may serve as useful serum tumor biomarkers in SCLC. It would now also be useful to determine if these serum biomarkers are altered in response to therapy for this disease. C1 Univ Chicago, Med Ctr, Pritzker Sch Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Boston Univ, Sch Med, Dept Med, Ctr Mol Stress Response, Boston, MA 02118 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Salgia, R (reprint author), Univ Chicago, Med Ctr, Pritzker Sch Med, Hematol Oncol Sect, MC2115,5841 S Maryland Ave, Chicago, IL 60637 USA. EM rsargia@medicine.bsd.uchicago.edu NR 35 TC 62 Z9 71 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2004 VL 24 IS 2C BP 1031 EP 1038 PG 8 WC Oncology SC Oncology GA 820JP UT WOS:000221385300001 PM 15154618 ER PT J AU Karamanakos, P Mitsiades, CS Lembessis, P Kontos, M Trafalis, D Koutsilieris, M AF Karamanakos, P Mitsiades, CS Lembessis, P Kontos, M Trafalis, D Koutsilieris, M TI Male breast adenocarcinoma in a prostate cancer patient following prolonged anti-androgen monotherapy SO ANTICANCER RESEARCH LA English DT Article DE prostate cancer; anti-androgen monotherapy; male breast cancer ID CARCINOMA; BRCA2; EPIDEMIOLOGY; CHROMOSOMES; MUTATIONS; THERAPY; LINKAGE; FAMILY; MEN AB We report the case of an 82-year-old male patient with a > 8-year history of prostate cancer (PrCa), who developed breast adenocarcinoma (BrCa) (Ki-67+ and negative for ER, PR, PSA and HER2/neu) after prolonged (similar to 7-year) antiandrogen (flutamide) monotherapy for locally advanced PrCa. Biochemical and molecular analyses showed hyperestrogenemia (serum estradiol = 266 pg/ml, with normal range < 74 pg/ml), germline BRCA-1 mutation (T to C at nucleotide 3232, in exon 11, causing Glu to Gly change at codon 1038) and chromosome 9 inversion (karyotype of 46,XY with inv(9) (p11q21)). Following bilateral mastectomy without adjuvant systemic therapy, the patient has been disease-free (from both BrCa and PrCa) for > 3 years. In contrast to LHRH-based hormonal therapies for PrCa, anti-androgen monotherapy causes hyper-estrogenemia due to the suppressed negative feedback loop of androgens on LHRH and LH production, stimulation of testicular androgen production and their intracrine transformation to estrogens in peripheral target tissues. In this case report, the hyperestrogenemia may have further increased the BrCa risk in a patient with other risk factors (BRCA-1 mutation and chromosome 9 inversion, which has been previously shown to impinge upon testicular function and intracrine balance of androgens vs. estrogens). This case report illustrates that PrCa patients receiving anti-androgen monotherapy may be at risk of BrCa, in the event of the concomitant presence of other genetically-determined predisposing factors, and indicates the importance of exercising caution against indiscriminate and prolonged use of anti-androgen monotherapy inpatients with fisk factors for male BrCa. C1 Univ Athens, Sch Med, Dept Expt Physiol, Athens 11527, Greece. Laikon Gen Hosp, Dept Surg, Div Surg Oncol, Athens 11527, Greece. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Koutsilieris, M (reprint author), Univ Athens, Sch Med, Dept Expt Physiol, 75 Micras Asias St, Athens 11527, Greece. EM mkouts@medscape.com NR 29 TC 11 Z9 12 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2004 VL 24 IS 2C BP 1077 EP 1081 PG 5 WC Oncology SC Oncology GA 820JP UT WOS:000221385300009 PM 15154626 ER PT J AU Chauhan, D Li, G Auclair, D Hideshima, T Podar, K Mitsiades, N Mitsiades, C Chen, LB Munshi, N Saxena, S Anderson, KC AF Chauhan, D Li, G Auclair, D Hideshima, T Podar, K Mitsiades, N Mitsiades, C Chen, LB Munshi, N Saxena, S Anderson, KC TI 2-Methoxyestardiol and bortezomib/proteasome-inhibitor overcome dexamethasone-resistance in multiple myeloma cells by modulating Heat Shock Protein-27 SO APOPTOSIS LA English DT Article DE apoptosis; bortezomib; drug-resistance; multiple myeloma ID CYTOCHROME-C; OLIGONUCLEOTIDE ARRAYS; DRUG-RESISTANCE; HSP27; PHOSPHORYLATION; HEAT-SHOCK-PROTEIN-27; EXPRESSION; APOPTOSIS; INDUCTION; RELEASE AB Multiple myeloma (MM) remains fatal despite all available therapies. Initial treatment with conventional drugs such as, Dexamethasone (Dex) effectively induces MM cell death; however, prolonged drug exposures results in the development of chemoresistance. Our prior study demonstrated that 2-Methoxyestradiol (2ME2) induces apoptosis in multiple myeloma ( MM) cells resistant to Dexamethasone (Dex). Here, we show the mechanism whereby 2ME2 overcomes Dex-resistance. The oligonucleotide array analysis demonstrates that Heat Shock Protein-27 (Hsp27) is upregulated in Dex-resistant, but not in Dex-sensitive MM cells. Proteomics analysis of Hsp27-immunocomplexes revealed the presence of actin in Dex-resistant, but not in Dex-sensitive cells. Biochemical interaction between Hsp27 and actin was examined by co-immunoprecipitation with anti-Hsp27 or actin Abs. Far western blot analysis using GST-Hsp27 fusion protein showed a direct association with actin both in vitro and in vivo. Importantly, 2ME2- or Bortezomib/Proteasome inhibitor (PS-341)-induced apoptosis in Dex-resistant MM cell lines and MM patient cells is associated with disruption of the Hsp27-actin complexes. Finally, blockade of Hsp27 by anti-sense strategy enhanced anti-MM activity of both 2ME2 and PS-341. These findings provide the clinical application of novel therapeutics targeting Hsp27 to improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. EM kenneth.anderson@dfci.harvard.edu FU NCI NIH HHS [P50 CA100707-01, CA 78814, CA 78373, P01 CA078378-06]; PHS HHS [50947] NR 26 TC 18 Z9 21 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD MAR PY 2004 VL 9 IS 2 BP 149 EP 155 DI 10.1023/B:APPT.0000018797.66067.6c PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 800UK UT WOS:000220053000005 PM 15004512 ER PT J AU Sung, N Takayama, K Collins, MT AF Sung, N Takayama, K Collins, MT TI Possible association of GroES and antigen 85 proteins with heat resistance of Mycobacterium paratuberculosis SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID AVIUM SUBSP PARATUBERCULOSIS; T-CELL RECOGNITION; CROHNS-DISEASE; THERMAL-RESISTANCE; ESCHERICHIA-COLI; MYCOLIC ACIDS; LISTERIA-MONOCYTOGENES; BICINCHONINIC ACID; SHOCK PROTEINS; TUBERCULOSIS AB Conflicting reports on the heat resistance of Mycobacterium paratuberculosis prompted an examination of the effect of culture medium on this property of the organism. M. paratuberculosis was cultured in three types of media (fatty acid-containing medium 7H9-OADC (oleic acid-albumin-dextrose-catalase supplement) and glycerol-containing media WR-GD and 7H9-GD [glycerol-dextrose supplement]) at pH 6.0. M. paratuberculosis grown under these three culture conditions was then tested for heat resistance in distilled water at 65degreesC. Soluble proteins and mycolic acids of M. paratuberculosis were evaluated by two-dimensional ellectrophoresis (2-DE) and thin-layer chromatography (TLC), respectively. The type of culture medium used significantly affected the heat resistance of M. paratuberculosis. The decimal reduction times at 65degreesC (D61-C values; times required to reduce the concentration of bacteria by a factor of 10 at 65degreesC) for M. paratuberculosis strains grown in 7H9-OADC were significantly higher than those for the organisms grown in WR-GD medium (P < 0.01). When the glycerol-dextrose supplement of WR was substituted for the fatty acid supplement (OADC) in 7H9 medium (resulting in 7H9-GD), the D-65degreesC value was significantly lower than that for the organism grown in 7H9-OADC medium (P = 0.022) but higher than that when it was cultured in WR-GD medium (P = 0.005). Proteomic analysis by 2-DE of soluble proteins extracted from M. paratuberculosis grown without heat stress in the three media (7H9-OADC, 7H9-GD, and WR-GD) revealed that seven proteins were more highly expressed in 7H9-OADC medium than in the other two media. When the seven proteins were subjected to matrix-assisted laser desorption ionization-mass spectrometric analysis, four of the seven protein spots were unidentifiable. The other three proteins were identified as GroES heat shock protein, alpha antigen, and antigen 85 complex B (Ag85B; fibronectin-binding protein). These proteins may be associated with the heat resistance of M. paratuberculosis. Alpha antigen and Ag85B are both trehalose mycolyltransferases involved in mycobacterial cell wall assembly. TLC revealed that 7H9-OADC medium supported production of more trehalose dimycolates and cell wall-bound mycolic acids than did WR-CD medium. The present study shows that in vitro culture conditions significantly affect heat resistance, cell wall synthesis, and protein expression of M. paratuberculosis and emphasize the importance of culture conditions on in vitro and ex vivo studies to estimate heat resistance. C1 Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53795 USA. Univ Wisconsin, Dept Microbiol & Immunol, Madison, WI 53705 USA. RP Collins, MT (reprint author), 2015 Linden Dr, Madison, WI 53706 USA. EM mcollin5@facstaff.wisc.edu NR 65 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2004 VL 70 IS 3 BP 1688 EP 1697 DI 10.1128/AEM.70.3.1688-1697.2004 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 802HO UT WOS:000220154800054 PM 15006794 ER PT J AU Singhal, AB AF Singhal, AB TI Postpartum angiopathy with reversible posterior leukoencephalopathy SO ARCHIVES OF NEUROLOGY LA English DT Article ID CEREBRAL VASOCONSTRICTION; ECLAMPSIA; ENCEPHALOPATHY; HYPERTENSION; VASOSPASM; MRI AB Background: Postpartum angiopathy (PPA) is a cerebral vasoconstriction syndrome of uncertain cause that affects large and medium-sized cerebral arteries. Postpartum angiopathy is frequently complicated by ischemic stroke. The reversible posterior leukoencephalopathy syndrome (RPLS) is a distinct clinical-radiological entity characterized by transient vasogenic edema on brain imaging. The pathophysiological features of RPLS are related to small-vessel dysfunction and breakdown of the blood-brain barrier. Objectives: To report the coexistence of PPA and RPLS in 4 patients and to discuss possible interrelationships between these 2 entities. Design: Four case reports and a review of the literature. Results: Four women developed a clinical-radiological syndrome overlapping PPA and eclampsia shortly after an uncomplicated pregnancy. All had acute severe ("thunderclap") headaches and hypertension. Three developed seizures. All patients had reversible angiographic narrowing of large and medium-sized cerebral arteries. Serial magnetic resonance imaging showed transient nonischemic brain lesions, resembling the lesions described in patients with RPLS. The results of extensive tests for cerebral vasculitis were negative. Conclusion: These cases, and the literature, suggest an interrelationship between RPLS and cerebral vasoconstriction syndromes such as PPA. C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Room VBK-802, Boston, MA 02114 USA. EM asinghal@partners.org NR 13 TC 117 Z9 126 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2004 VL 61 IS 3 BP 411 EP 416 DI 10.1001/archneur.61.3.411 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 801TQ UT WOS:000220118600016 PM 15023819 ER PT J AU Andreoli, CM Hatton, M Semple, JP Soukiasian, SH Fay, AM AF Andreoli, CM Hatton, M Semple, JP Soukiasian, SH Fay, AM TI Perilimbal conjunctival schwannoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BULBAR CONJUNCTIVA C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Fay, AM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Aaron_Fay@meei.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2004 VL 122 IS 3 BP 388 EP 389 DI 10.1001/archopht.122.3.388 PG 2 WC Ophthalmology SC Ophthalmology GA 801CY UT WOS:000220075200018 PM 15006858 ER PT J AU Calvanio, R Williams, R Burke, DT Mello, J Lepak, P Al-Adawi, S Shah, MK AF Calvanio, R Williams, R Burke, DT Mello, J Lepak, P Al-Adawi, S Shah, MK TI Acquired brain injury, visual attention, and the useful field of view test: A pilot study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE attention; brain injuries; rehabilitation AB Objective: To compare the findings of the Useful Field of View (UFOV) test with those of conventional neuropsychologic tests to determine the utility of the UFOV test as a measure of attention in a population with brain injury. Design: Cohort study. Setting: Freestanding rehabilitation hospital. Participants: Fifteen inpatients with severe brain injury. Interventions: Not applicable. Main Outcome Measures: UFOV test, FIM(TM) instrument, length of stay (LOS), and standard neuropsychologic testing. Results: The UFOV subtest UF2 correlated strongly with the other 2 subtests, UF1 and UF3. The UF2 subtest correlated most strongly with paper and pencil tests of visual attention. The UF2 predicted 52% of the FIM change and 60% of the LOS variance, second only to admission FIM score, which predicted 75% and 80% of FIM change and LOS variance, respectively. Conclusions: Among the patients in our study, the UFOV test can be used to determine the visual divided attention of patients with acquired brain injury. The results also showed that the UFOV test correlated with LOS and FIM change in patients with acquired brain injury recovering in a rehabilitation facility. Because the UFOV test is much more quickly administered and scored than other measures of attention and divided attention, these results suggest that the UFOV test may provide an easy means to measure a critical variable in the population with head injury. C1 Spaulding Rehabil Hosp, Dept PM&R, Boston, MA 02114 USA. VA Boston Hlth Care Syst, Geriatr Neuropsychol Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA 02115 USA. Sultan Qaboos Univ, Coll Med, Al Khoud, Oman. RP Burke, DT (reprint author), Spaulding Rehabil Hosp, Dept PM&R, 125 Nashua St, Boston, MA 02114 USA. OI Al-Adawi, Samir/0000-0002-9858-5582 NR 13 TC 8 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2004 VL 85 IS 3 BP 474 EP 478 DI 10.1016/S0003-9993(03)00469-6 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 801AC UT WOS:000220067800020 PM 15031836 ER PT J AU Costenbader, KH Kim, DJ Peerzada, J Lockman, S Nobles-Knight, D Petri, M Karlson, EW AF Costenbader, KH Kim, DJ Peerzada, J Lockman, S Nobles-Knight, D Petri, M Karlson, EW TI Cigarette smoking and the risk of systemic lupus erythematosus - A meta-analysis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; SILICONE BREAST IMPLANTS; RHEUMATOID-ARTHRITIS; ALCOHOL-CONSUMPTION; GRAVES OPHTHALMOPATHY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; AUTOIMMUNE-DISEASES; UNITED-STATES; SEX-HORMONES AB Objective. Existing studies present conflicting evidence for the role of cigarette smoking as a risk factor in the development of systemic lupus erythematosus (SLE). We performed an extensive search of the medical literature for all studies examining this relationship, and performed a meta-analysis to arrive at a more precise estimate of effect. Methods. We performed a computerized literature search for all studies (in all languages), using Medline and EMBASE (1966 to present) and the Cochrane Collaboration database, and completed hand searches of relevant bibliographies and abstracts of conference proceedings. Several investigators systematically extracted data from the relevant studies. Unpublished data were obtained from the author of one abstract. Studies were examined in aggregate for heterogeneity and publication bias. The relationships of current smoking and past smoking (prior to the onset of SLE) to development of SLE were analyzed separately. Results. Fifty-two studies were identified and chosen for detailed review. Of these, 9 (7 case-control and 2 cohort studies) were appropriate for inclusion in our meta-analyses. For current smokers compared with nonsmokers, the odds ratio (OR) for development of SLE was significantly elevated (OR 1.50, 95% confidence interval [95% CI] 1.09-2.08). Former smokers, compared with nonsmokers, did not demonstrate an increased risk of SLE (OR 0.98, 95% CI 0.75-1.27). Several subgroups were also analyzed. Conclusion. Our meta-analysis of the 7 existing case-control and 2 cohort studies revealed a small but statistically significant association between current smoking and development of SLE. However, no association between past smoking and development of SLE was observed. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Robert B Brigham Arthrit & Musculoskeletal Dis Cl, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Sch Publ Hlth, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Pfizer Inc, Clin Practice Outcomes Res, Chicago, IL USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP Costenbader, KH (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM KCostenbader@Partners.Org FU BHP HRSA HHS [T32-PE-10018]; NCRR NIH HHS [M01-RR-00052]; NIAMS NIH HHS [AR-43727, K08-AR-02074-0, P01-AR-36308]; NICHD NIH HHS [K23-HD-40451, R01-HD-044391] NR 56 TC 136 Z9 137 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 2004 VL 50 IS 3 BP 849 EP 857 DI 10.1002/art.20049 PG 9 WC Rheumatology SC Rheumatology GA 801TW UT WOS:000220119200023 PM 15022327 ER PT J AU Blutt, SE Conner, ME AF Blutt, SE Conner, ME TI Kinetics of rotavirus infection in mice are not altered in a ground-based model of spaceflight SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article DE virus; hindlimb unloading; immunity; mucosal; enteric; intestine; microgravity ID LISTERIA-MONOCYTOGENES INFECTION; SPACE-FLIGHT; ANTIORTHOSTATIC SUSPENSION; IMMUNE-SYSTEM; DURATION MISSIONS; MOUSE MODEL; WEIGHTLESSNESS; RESISTANCE; RESPONSES AB Introduction: The effect of simulated spaceflight conditions using the hindlimb unloading model on mucosal immune responses has not been examined. Therefore, we determined whether clearance, protection, and the antibody responses to an enteric pathogen, rotavirus, were altered under simulated spaceflight conditions. Methods: Groups of mice were either restrained and hindlimb unloaded, restrained without hindlimb unloading, or housed under standard conditions for either 4 or 14 d prior to and an additional 10 d following inoculation with ECwt murine rotavirus. An additional group of mice previously infected with rotavirus was housed under the three conditions for either 4 or 14 d prior to a rotavirus challenge. Results: Hindlimb unloading of mice did not alter clearance of a primary rotavirus infection compared with controls nor were there differences in protection from rotavirus challenge 42 d later between the three groups, all housed under standard conditions. There were no differences in protection from rotavirus challenge in mice that were hindlimb unloaded during the challenge infection compared with controls. The generation of rotavirus-specific fecal antibodies, as measured by enzyme-linked immunosorbent assay (ELISA), was not significantly different between any of the groups following either primary or challenge rotavirus infection. However, serum rotavirus-specific IgG1 antibody was not induced in mice housed under normal conditions and challenged under hindlimb unloading conditions compared with controls. Discussion: These data are the first examination of the mucosal immune response to an enteric viral pathogen under simulated spaceflight conditions and indicate that rotavirus immunity was not impacted in this model. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Med Res Serv, Dept Vet Affairs Med Ctr, Houston, TX USA. RP Conner, ME (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. EM mconner@bcm.tmc.edu NR 24 TC 2 Z9 2 U1 0 U2 0 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD MAR PY 2004 VL 75 IS 3 BP 215 EP 219 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 809OJ UT WOS:000220645700004 PM 15018288 ER PT J AU Bauer, KA AF Bauer, KA TI Fondaparinux: a new synthetic and selective inhibitor of Factor Xa SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE fondaparinux; heparin; pentasaccharide; pharmacokinetics; thromboprophylaxis; venous thromboembolism; surgery; acute coronary syndromes ID RANDOMIZED DOUBLE-BLIND; MAJOR ORTHOPEDIC-SURGERY; HIP-REPLACEMENT SURGERY; DEEP-VEIN THROMBOSIS; VENOUS THROMBOEMBOLISM; PENTASACCHARIDE FONDAPARINUX; HEALTHY-VOLUNTEERS; ANTITHROMBIN-III; POSTOPERATIVE FONDAPARINUX; BINDING PENTASACCHARIDE AB Fordaparinux (Arixtra(R)) is the first synthetic selective Factor Xa inhibitor. Its efficacy and safety in the prevention of venous thromboembolism (VTE) was first studied in patients undergoing major orthopedic surgery, a setting in the highest risk category for postoperative thrombotic complications. Low-molecular-weight heparins are frequently used in this setting, but the rates of VTE still range between 15% and 33%. In large clinical trials, fordaparinux started 6 hours postoperatively was significantly more effective than enoxaparin in preventing WE in patients undergoing total hip replacement, total knee replacement or hip fracture surgery. The benefit of extended fondaparinux prophylaxis after hip fracture surgery was also investigated. Other trials have demonstrated that fondaparinux is efficacious in the prevention of WE in other patient populations at risk of thrombosis and in the treatment of symptomatic VTE. C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Hematol Sect, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. EM kbauer@bidmc.harvard.edu NR 51 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2004 VL 17 IS 1 BP 89 EP 104 DI 10.1016/j.beha.2004.03.004 PG 16 WC Hematology SC Hematology GA 891VP UT WOS:000226609400007 PM 15171960 ER PT J AU Kim, MR Tilly, JL AF Kim, MR Tilly, JL TI Current concepts in Bcl-2 family member regulation of female germ cell development and survival SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE apoptosis; cell death; ovary; germ cell; Bcl-2; Bax; gene knockout; fertility ID ARYL-HYDROCARBON RECEPTOR; POLYCYCLIC AROMATIC-HYDROCARBONS; OVARIAN GRANULOSA-CELLS; GENE-EXPRESSION; PRIMORDIAL FOLLICLES; FOLLICULAR ATRESIA; PRENATAL OOGENESIS; BH3-ONLY PROTEINS; OOCYTE APOPTOSIS; RAT OVARY AB Since the cloning of the bcl-2 gene in 1985, considerable progress has been made in elucidating the ftinction of Bcl-2 and related proteins in controlling apoptosis. Although much of this work initially relied on the ectopic expression of bcl-2 gene family members in cell lines in vitro, a number of genetically manipulated mice have been generated to better understand the in vivo significance of specific family members to organ development and homeostasis. Of the many tissues that exhibit apoptosis at some point during fetal or postnatal life, the female gonads arguably possess one of the highest and most protracted incidences of apoptosis, associated with development and maturation of the germ line. Moreover, female germ cells (oocytes) are, for as-yet poorly understood reasons, extremely vulnerable to a host of pathological insults, such as anti-cancer therapies, that ultimately cause premature ovarian failure and infertility due to accelerated oocyte death. Accordingly, efforts to understand the occurrence and regulation of apoptosis in the ovary are of considerable importance from both biological and clinical perspectives. This review will highlight what is known of apoptosis in the female gonads, and the role that Bcl-2 family members play in regulating this process. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, VBK113-GYN,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU NIA NIH HHS [R01-AG12279]; NIEHS NIH HHS [R01-ES08430] NR 78 TC 48 Z9 57 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR 1 PY 2004 VL 1644 IS 2-3 BP 205 EP 210 DI 10.1016/j.bbamcr.2003.10.012 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 801VE UT WOS:000220122600014 PM 14996504 ER PT J AU Kircher, MF Weissleder, R Josephson, L AF Kircher, MF Weissleder, R Josephson, L TI A dual fluorochrome probe for imaging proteases SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CATHEPSIN-B; MACROPHAGES; NANOPARTICLES; CALCIUM; AGENT; CELLS AB Near-infrared fluorescence (NIRF) optical probes have been able to provide a noninvasive assessment of enzyme activity for a number of different enzymes and types of pathology. Here we describe a dual fluorochrome enzyme-activatable probe featuring one NIRF fluorochrome that is activated by protease activity and a second fluorochrome that is protease resistant and serves as an internal standard. The probe was prepared by attaching Cy7 directly to an amino-CLIO, an amine functional cross-linked iron oxide (CLIO) nanoparticle carrier, in a protease resistant manner. Cy5.5 was attached to a protease sensitive polyarginine peptide spacer, also attached to amino-CLIO. In vitro and in vivo the ratio of the Cy5.5 to Cy7 fluorescence was increased by protease, reflecting the increase in Cy5.5 fluorescence by protease in the vicinity of the probe. In vitro and in vivo the absolute values of the Cy5.5 and Cy7 fluorescence reflected lesion size and the distance of lesions from the surface, while the ratio of Cy5.5 to Cy7 fluorescence obtained was constant and independent of lesion size and depth. The dual fluorochrome probe, and related dual wavelength imaging method, represents a novel approach for imaging protease activity in vivo. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149 13th St 5406, Charlestown, MA 02129 USA. EM ljosephson@partners.org RI Peng, Chunwei/F-6788-2010 FU NCI NIH HHS [P50CA8635]; NIBIB NIH HHS [R01 EB 001872] NR 26 TC 96 Z9 96 U1 2 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2004 VL 15 IS 2 BP 242 EP 248 DI 10.1021/bc034151d PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 804FH UT WOS:000220284100003 PM 15025519 ER PT J AU Thermenos, HW Seidman, LJ Breiter, H Goldstein, JM Goodman, JM Poldrack, R Faraone, SV Tsuang, MT AF Thermenos, HW Seidman, LJ Breiter, H Goldstein, JM Goodman, JM Poldrack, R Faraone, SV Tsuang, MT TI Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: A pilot study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; genetics; functional magnetic resonance imaging; working memory; interference; cingulate ID DORSOLATERAL PREFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; AMYGDALA-HIPPOCAMPAL VOLUME; STROOP TASK-PERFORMANCE; BRAIN ACTIVATION; NEUROPSYCHOLOGICAL FUNCTION; 1ST-DEGREE RELATIVES; RESPONSE CONFLICT; MATCHING FALLACY; GENETIC RISK AB Background: First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks. We used functional magnetic resonance imaging (fMRI) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex (PFC), thalamus, hippocampus, and anterior cingulate during a working memory task requiring interference resolution. Methods: Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory, verbal working memory version of the Continuous Performance Test during fMRI. An asymmetric, spin-echo, T2*-weighted sequence (15 contiguous, 7-mm axial slices) was acquired on a full-body MR scanner. Data were analyzed by Statistical Parametric Mapping (SPM). Results: Compared with control subjects, relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus. When task performance was controlled, relatives showed significantly greater activation in the anterior cingulate. When effects of other potentially cor founding variables were controlled, relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate. Conclusions: This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis. These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia. C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Thermenos, HW (reprint author), Massachusetts Gen Hosp, Bldg 149,Room 2602E,13th St, Boston, MA 02129 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH- 43518, MH-16259, MH-46318, MH63951, R25 MH 60485] NR 98 TC 83 Z9 87 U1 2 U2 3 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 MAR 1 PY 2004 VL 55 IS 5 BP 490 EP 500 DI 10.1016/j.biopsych.2003.11.014 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 779HV UT WOS:000189290000009 PM 15023577 ER PT J AU Wynn, JK Dawson, ME Schell, AM McGee, M Salveson, D Green, MF AF Wynn, JK Dawson, ME Schell, AM McGee, M Salveson, D Green, MF TI Prepulse facilitation and prepulse inhibition in schizophrenia patients and their unaffected siblings SO BIOLOGICAL PSYCHIATRY LA English DT Article DE startle; prepulse inhibition; prepulse facilitation; orienting; schizophrenia; endophenotypic marker ID SCHIZOTYPAL PERSONALITY-DISORDER; CONDUCTANCE ORIENTING RESPONSE; STARTLE EYEBLINK MODIFICATION; ATTENTIONAL PROCESSES; MISMATCH NEGATIVITY; REFLEX MODIFICATION; ACOUSTIC STARTLE; GATING DEFICITS; RELATIVES; ABNORMALITIES AB Background: Deficits in schizophrenia patients and their first-degree relatives have been reported in prepulse inhibition (PPI), a phenomenon that measures an early stage of information processing (sensorimotor gating). It is less clear whether these information processing deficits extend to prepulse facilitation (PPF), which measures a later stage of generalized alerting or orienting. Methods. This study examined three separate issues: first, whether schizophrenia patients have deficits in PPI and PPF; second, whether the siblings of patients show deficits in these processes; and third, whether prepulse duration influences the degree of the deficits. These issues were examined in 76 schizophrenia patients, 36 of their siblings, and 41 normal control subjects. Results: Patients and siblings did not differ from control subjects in PPI, perhaps due to the use of different procedural parameters compared with other laboratories that have consistently found PPI deficits in schizophrenia patients. Patients and their siblings produced significantly less PPF than control subjects. For both PPI and PPF, prepulse duration was not a significant factor. Conclusions: These results imply that PPF deficits reveal a generalized alerting or orienting deficit that is present in both schizophrenia patients and their siblings, suggesting that this deficit may be tapping an endophenotypic vulnerability factor. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Occidental Coll, Dept Psychol, Los Angeles, CA 90041 USA. RP Wynn, JK (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 210, Los Angeles, CA 90073 USA. RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIMH NIH HHS [MH14584, MH-46433, MH43292] NR 44 TC 47 Z9 47 U1 0 U2 3 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 MAR 1 PY 2004 VL 55 IS 5 BP 518 EP 523 DI 10.1016/j.biopsych.2003.10.018 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 779HV UT WOS:000189290000012 PM 15023580 ER PT J AU Forman, SD Dougherty, GG Casey, BJ Siegle, GJ Braver, TS Barch, DM Stenger, VA Wick-Hull, C Pisarov, LA Lorensen, E AF Forman, SD Dougherty, GG Casey, BJ Siegle, GJ Braver, TS Barch, DM Stenger, VA Wick-Hull, C Pisarov, LA Lorensen, E TI Opiate addicts lack error-dependent activation of rostral anterior cingulate SO BIOLOGICAL PSYCHIATRY LA English DT Article DE substance-related disorders; heroin dependence; decision making; choice behavior; impulsivity; personality ID EVENT-RELATED FMRI; PREFRONTAL CORTEX; FUTURE CONSEQUENCES; IMPULSE CONTROL; HEROIN-ADDICTS; PERSONALITY; SMOKERS; DISORDER; SMOKING; DAMAGE AB Background: Healthy individuals performing response suppression tasks activate anterior cingulate cortex with occurrence of false alarm error responses to nontargets. Fundamental questions include whether this error-related activation provides a signal contributing to behavioral control and given generally poorer performance on such tasks by addicts, whether this signal is disrupted in addiction. Methods: We used rapid, event-related functional magnetic resonance imaging to study 13 individuals with opiate dependence and 26 healthy control individuals performing a Go/NoGo task. Results: Compared with controls, opiate addicts exhibited an attenuated anterior cingulate cortex error signal and significantly poorer task performance. In controls, the individual level of event-related anterior cingulate cortex activation accompanying false alarm error positively predicted task performance, particularly sensitivity in discriminating targets from nontargets. Conclusions: The attenuation of this error signal in anterior cingulate cortex may play a role in loss of control in addiction and other forms of impulsive behavior. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Vet Affairs, Pittsburgh, PA USA. Cornell Univ, Weill Med Coll, Sackler Inst Dev Psychobiol, New York, NY 10021 USA. Washington Univ, Dept Psychol, St Louis, MO 63130 USA. RP Forman, SD (reprint author), Vet Affairs Pittsburgh HCS, Highland Dr Div, 7180 Highland Dr, Pittsburgh, PA 15206 USA. RI Barch, Deanna/G-8638-2013; OI Braver, Todd/0000-0002-2631-3393 FU NIDA NIH HHS [R29 DA 11721]; NIMH NIH HHS [R01 MH066031] NR 54 TC 138 Z9 143 U1 8 U2 21 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 MAR 1 PY 2004 VL 55 IS 5 BP 531 EP 537 DI 10.1016/j.biopsych.2003.09.011 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 779HV UT WOS:000189290000014 PM 15023582 ER PT J AU Salva, A Hardy, MP Wu, XF Sottas, CM MacLaughlin, DT Donahoe, PK Lee, MM AF Salva, A Hardy, MP Wu, XF Sottas, CM MacLaughlin, DT Donahoe, PK Lee, MM TI Mullerian-inhibiting substance inhibits rat Leydig cell regeneration after ethylene dimethanesulphonate ablation SO BIOLOGY OF REPRODUCTION LA English DT Article DE Leydig cells; male reproductive tract; mechanisms of hormone action; testis; testosterone ID LUTEINIZING-HORMONE RECEPTOR; FOLLICLE-STIMULATING-HORMONE; SELECTIVE DESTRUCTION; ADULT-RAT; SEMINIFEROUS EPITHELIUM; MOLECULAR-MECHANISMS; SULFONATE TREATMENT; SEXUAL DEVELOPMENT; TRANSGENIC MICE; TESTIS AB The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered by intratesticular injection for 4 days (Days 11-14 after EDS). On Days 15 and 35 after EDS (1 and 21 days post-MIS injections), endocrine function was assessed and testes were collected for stereology, immunohistochemistry, and assessment of proliferation and steroidogenesis. Although serum testosterone and luteinizing hormone (LH) were no different, intratesticular testosterone was higher on Day 35 in MIS-treated animals. At both time points, intratesticular 5alpha-androstan-3alpha,17beta-diol concentrations were much higher than that of testosterone. MIS-treated animals had fewer mesenchymal precursors on Day 15 and fewer differentiated Leydig cells on Day 35 with decreased numbers of BrdU+ nuclei. Apoptotic interstitial cells were observed only in the MIS-treated testes, not in the vehicle-treated group on Day 15. These data suggest that MIS inhibits regeneration of Leydig cells in EDS-treated rats by enhancing apoptotic cell death as well as by decreasing proliferative capacity. C1 Duke Univ, Med Ctr, Div Pediat Endocrine, Durham, NC 27710 USA. Populat Council, New York, NY 10021 USA. Rockefeller Univ, New York, NY 10021 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Duke Univ, Med Ctr, Div Pediat Endocrinol, 308 Bell Bldg,Box 3080,Bell Res Dr, Durham, NC 27710 USA. EM Lee00140@mc.duke.edu OI Lee, Mary/0000-0002-7204-4884 FU NICHD NIH HHS [HD01367, HD32588, HD3678] NR 46 TC 29 Z9 31 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2004 VL 70 IS 3 BP 600 EP 607 DI 10.1095/biolreprod.103.021550 PG 8 WC Reproductive Biology SC Reproductive Biology GA 776ZX UT WOS:000189150400008 PM 14585814 ER PT J AU Zaleskas, JM Kinner, B Freyman, TM Yannas, IV Gibson, LJ Spector, M AF Zaleskas, JM Kinner, B Freyman, TM Yannas, IV Gibson, LJ Spector, M TI Contractile forces generated by articular chondrocytes in collagen-glycosaminoglycan matrices SO BIOMATERIALS LA English DT Article DE articular chondrocytes; collagen-glycosaminoglycan scaffold; contraction; smooth muscle actin ID SMOOTH-MUSCLE ACTIN; MESENCHYMAL STEM-CELLS; PROTEIN-KINASE; GAG MATRIX/; IN-VITRO; CARTILAGE DIFFERENTIATION; FIBROBLAST CONTRACTION; STAUROSPORINE; EXPRESSION; INHIBITOR AB The objective of the Study was to directly measure the force of contraction of adult articular chondrocytes and to examine their contractile behavior in collagen-glycosaminoglycan analogs of extracellular matrix by live cell imaging in vitro. The contractile forces generated by passages 2 and 3 adult canine articular chondrocytes were measured using a cell force monitor. The contractile behavior of the cells was also directly imaged as they were cultured in collagen-glycosaminoglycan scaffolds. Passage 2 cells seeded in a collagen-glycosaminoglycan scaffold were capable of generating a force of 0.3 nN/cell. Chondrocytes subcultured through a third passage generated a force twice that level, paralleling the increase in the alpha-smooth muscle actin (SMA) content of the cells as demonstrated by Western blot analysis. Treatment of passage 3 cells with staurosporine reduced the force of contraction by approximately one-half, reflecting the effects of this agent in reducing the SMA content of the cells and disrupting the microfilaments. These values compare with 1 nN previously reported for lapine dermal fibroblasts of passage 5-7, using the same apparatus. Direct live cell imaging documented the contractile behavior of the articular chondrocytes in the collagen-glycosaminoglycan matrix in the time frame in which the force was directly measured in the cell force monitor. This imaging demonstrated how the cells acted individually and in unison to buckle the collagen struts making up the matrix. Adult articular chondrocytes are capable of generating a SMA-enabled force of contraction sufficient to model extracellular matrix molecules. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Spector, M (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. RI Gibson, Lorna/K-4738-2012; OI /0000-0001-7559-7815 NR 33 TC 40 Z9 42 U1 2 U2 6 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 MAR-APR PY 2004 VL 25 IS 7-8 BP 1299 EP 1308 DI 10.1016/j.biomaterials.2003.08.005 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 753PJ UT WOS:000187239500018 PM 14643604 ER PT J AU Han, KE Catalano, PJ Senchaudhuri, P Mehta, C AF Han, KE Catalano, PJ Senchaudhuri, P Mehta, C TI Exact analysis of dose response for multiple correlated binary outcomes SO BIOMETRICS LA English DT Article DE binary data; exact test; multiple outcomes; network algorithm ID FUNCTIONAL OBSERVATIONAL BATTERY; LOGISTIC-REGRESSION; MODELS AB The neurotoxicity of a substance is often tested using animal bioassays. In the functional observational battery, animals are exposed to a test agent and multiple outcomes are recorded to assess toxicity, using approximately 40 animals measured on up to 30 different items. This design gives rise to a challenging statistical problem: a large number of outcomes for a small sample of subjects. We propose an exact test for multiple binary outcomes, under the assumption that the correlation among these items is equal. This test is based upon an exponential model described by Molenberghs and Ryan (1999, Environmetrics 10, 279300) and extends the methods developed by Corcoran et al. (2001, Biometrics 57, 941-948) who developed an exact test for exchangeably correlated binary data for groups (clusters) of correlated observations. We present a method that computes an exact p-value testing for a joint dose-response relationship. An estimate of the parameter for dose response is also determined along with its 95% confidence bound. The method is illustrated using data from a neurotoxicity bioassay for the chemical perchlorethylene. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Cytel Software Corp, Cambridge, MA 02139 USA. RP Han, KE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM khan@jimmy.harvard.edu FU NIEHS NIH HHS [T32 ES07142-18, ES06900] NR 16 TC 10 Z9 10 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2004 VL 60 IS 1 BP 216 EP 224 DI 10.1111/j.0006-341X.2004.00152.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 805RW UT WOS:000220384400026 PM 15032792 ER PT J AU Thibodeau, SA Fang, R Joung, JK AF Thibodeau, SA Fang, R Joung, JK TI High-throughput beta-galactosidase assay for bacterial cell-based reporter systems SO BIOTECHNIQUES LA English DT Article ID ENZYME ASSAYS; PERMEABILIZATION; SELECTION; GROWTH C1 Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, 149 13th St,7th Floor, Charlestown, MA 02129 USA. EM jjoung@partners.org FU NIDDK NIH HHS [K08DK02883]; NIH HHS [DP1 OD006862] NR 11 TC 49 Z9 50 U1 1 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2004 VL 36 IS 3 BP 410 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802DI UT WOS:000220143800008 PM 15038156 ER PT J AU LeBlanc, R Hideshima, T Catley, LP Shringarpure, R Burger, R Mitsiades, N Mitsiades, C Cheema, P Chauhan, D Richardson, PG Anderson, KC Munshi, NC AF LeBlanc, R Hideshima, T Catley, LP Shringarpure, R Burger, R Mitsiades, N Mitsiades, C Cheema, P Chauhan, D Richardson, PG Anderson, KC Munshi, NC TI Immunomodulatory drug costimulates T cells via the B7-CD28 pathway SO BLOOD LA English DT Article ID MULTIPLE-MYELOMA CELLS; THALIDOMIDE ANALOGS; PROTEIN; DISEASE; PROLIFERATION; LYMPHOCYTES; ACTIVATION; RESISTANCE; INDUCTION; RESPONSES AB Although thalidomide (Thal) does not directly induce T-cell activation, it increases proliferation of T cells following CD3 activation. In this study, we examined the immunomodulatory effects of a more potent analog of Thal, immunomodulatory drug (IMID), on T cells. Although IMiD3 does not directly stimulate proliferation of normal donor CD3(+) T cells, it significantly costimulates proliferation of CD3(+) T cells induced by CD3 ligation (stimulation index [SI], 2.4), immature dendritic cells (DCs; SI, 2.1), and mature DCs (SI, 2.6). T-cell proliferation triggered by DCs was abrogated by cytotoxic T lymphocyte antigen 4-immunoglobulin (CTLA-4-Ig), and IMiD3 partially overcomes this inhibitory effect. IMiD3 also overcomes the inhibitory effects of CTLA-4-Ig on Epstein-Barr virus (EBV) and influenza (Flu)-specific CD4 and CD8 T-cell responses, as measured by cytokine capture and enzyme-linked immunosorbent spot (ELISPOT) assay. IMiD3 did not induce up-regulation of CD28 expression on T cells, or of CD80-CD86 expression on dendritic cells. Importantly, IMiD3 triggers tyrosine phosphorylation of CD28 on T cells, followed by activation of nuclear factor kappaB (NF-kappaB), a known downstream target of CD28 signaling. These results therefore define the costimulatory mechanism whereby IMiD3 induces T-cell activation and provide the cellular and molecular basis for use of IMiD3 as an adjuvant in immunotherapeutic treatment strategies for multiple myeloma. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, 44 Binney St,M557, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU PHS HHS [P01-78378, R01-50947] NR 25 TC 161 Z9 166 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2004 VL 103 IS 5 BP 1787 EP 1790 DI 10.1182/blood-2003-02-0361 PG 4 WC Hematology SC Hematology GA 778NM UT WOS:000189247700040 PM 14512311 ER PT J AU Munshi, NC Hideshima, T Carrasco, D Shammas, M Auclair, D Davies, F Mitsiades, N Mitsiades, C Kim, RS Li, C Rajkumar, SV Fonseca, R Bergsagel, L Chauhan, D Anderson, KC AF Munshi, NC Hideshima, T Carrasco, D Shammas, M Auclair, D Davies, F Mitsiades, N Mitsiades, C Kim, RS Li, C Rajkumar, SV Fonseca, R Bergsagel, L Chauhan, D Anderson, KC TI Identification of genes modulated in multiple myeloma using genetically identical twin samples SO BLOOD LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; CHROMOSOME-13 ABNORMALITIES; UNDETERMINED SIGNIFICANCE; OLIGONUCLEOTIDE ARRAYS; MONOCLONAL GAMMOPATHY; PLASMA-CELLS; THERAPEUTIC IMPLICATIONS; TELOMERASE ACTIVITY AB Genetic heterogeneity between individuals confounds the comparison of gene profiling of multiple myeloma (MM) cells versus normal plasma cells (PCs). To overcome this barrier, we compared the gene expression profile of CD138(+) MM cells from a patient bone marrow (BM) sample with CD138(+) PCs from a genetically identical twin BM sample using microarray profiling. Two hundred and ninety-six genes were up-regulated and 103 genes were down-regulated at least 2-fold in MM cells versus normal twin PCs. Highly expressed genes in MM cells included cell survival pathway genes such as mcl-1, dad-1, caspase 8, and FADD-like apoptosis regulator (FLIP), oncogenes/transcriptional factors such as Jun-D, Xbp-1, calmodulin, Calnexin, and FGFR-3, stress response and ubiquitin/proteasome pathway-related genes and various ribosomal genes reflecting increased metabolic and translational activity. Genes that were down-regulated in MM cells versus healthy twin PCs included RAD51, killer cell immunoglobulin-like receptor protein, and apoptotic protease activating factor. Microarray results were further confirmed by Western blot analyses, immunohistochemistry, fluorescent in situ hybridization (FISH), and functional assays of telomerase activity and bone marrow anglogenesis. This molecular profiling provides potential insights into mechanisms of malignant transformation in MM. For example, FGFR3, xbp-1, and both mcl-1 and dad-1 may mediate transformation, differentiation, and survival, respectively, and may have clinical implications. By identifying genes uniquely altered in MM cells compared with normal PCs in an identical genotypic background, the current study provides the framework to identify novel therapeutic targets. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. Mayo Clin, Med Ctr, Rochester, MN USA. Cornell Univ, Weil Coll, New York, NY USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,M557, Boston, MA 02115 USA. EM nikhil_munshi@dfci.harvard.edu RI Bergsagel, Peter/A-7842-2011; OI Bergsagel, Peter/0000-0003-1523-7388; Fonseca, Rafael/0000-0002-5938-3769; Rajkumar, S. Vincent/0000-0002-5862-1833 FU PHS HHS [P50-100707, P01-78378, R01-50947] NR 53 TC 92 Z9 98 U1 0 U2 3 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 MAR 1 PY 2004 VL 103 IS 5 BP 1799 EP 1806 DI 10.1182/blood-2003-02-0402 PG 8 WC Hematology SC Hematology GA 778NM UT WOS:000189247700043 PM 12969976 ER PT J AU Barata, JT Boussiotis, VA Yunes, JA Ferrando, AA Moreau, LA Veiga, JP Sallan, SE Look, AT Nadler, LM Cardoso, AA AF Barata, JT Boussiotis, VA Yunes, JA Ferrando, AA Moreau, LA Veiga, JP Sallan, SE Look, AT Nadler, LM Cardoso, AA TI IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SEVERE COMBINED IMMUNODEFICIENCY; CYCLE PROGRESSION; PHOSPHATIDYLINOSITOL-3 KINASE; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY; EARLY CYTOREDUCTION; TRANSGENIC MICE; GROWTH-FACTOR AB The specific targeting of critical signaling molecules may provide efficient therapies for T-cell acute lymphoblastic leukemia (T-ALL). However, target identification and drug development are limited by insufficient numbers of primary T-ALL cells and by their high rate of spontaneous apoptosis. We established a human interleukin-7 (IL-7)-dependent T-ALL cell line, TAIL7, that maintains several biologic and signaling properties of its parental leukemia cells. TAIL7 cells are pre-TAIL cells that proliferate in response to IL-7 and IL-4. IL-7 stimulation of TAIL7 cells prevents spontaneous in vitro apoptosis and induces cell activation and cell cycle progression. The signaling events triggered by IL-7 include down-regulation of p27(kip1) and hyperphosphorylation of retinoblastorna protein (Rb). Stimulation of TAIL7 cells by IL-7 leads to phosphorylation of Janus kinase 3 (JAK3), signal transducer and activator of transcription 5 (STAT5), Akt/PKB (protein kinase B), and extracellular-regulated kinase 1 and 2 (Erk1/2). Importantly, specific blockade of JAK3 by its inhibitor WHI-P131 abrogates the IL-7-mediated proliferation and survival of TAIL7 cells, suggesting that activation of JAK3 is critical for IL-7 responsiveness by these cells. Because TAIL7 cells seem to be a biologic surrogate for primary leukemia T cells, this cell line constitutes a valuable tool for the study of the signaling pathways implicated in T-ALL. Exploitation of this cell line should allow the identification of molecular targets and promote the rational design and validation of antileukemia signaling inhibitors. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Lisbon, Sch Med, Unit Tumor Biol, Inst Mol Med, Lisbon, Portugal. RP Cardoso, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Rm D-540B,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu RI Barata, Joao/D-9181-2015 OI Barata, Joao/0000-0002-4826-8976 FU NCI NIH HHS [P01-CA68484] NR 56 TC 29 Z9 29 U1 0 U2 2 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 MAR 1 PY 2004 VL 103 IS 5 BP 1891 EP 1900 DI 10.1182/blood-2002-12-3861 PG 10 WC Hematology SC Hematology GA 778NM UT WOS:000189247700055 PM 14615384 ER PT J AU Ferrando, AA Herblot, S Palomero, T Hansen, M Hoang, T Fox, EA Look, AT AF Ferrando, AA Herblot, S Palomero, T Hansen, M Hoang, T Fox, EA Look, AT TI Biallelic transcriptional activation of oncogenic transcription factors in T-cell acute lymphoblastic leukemia SO BLOOD LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; EXPRESSION; CHILDHOOD; OCCUR; HOX11 AB Aberrant expression of transcription factor oncogenes such as HOX11, HOX11L2, TAL1/SCL, LYL1, LMO1, and LMO2 can be detected in lymphoblasts from up to 80% of patients with acute T-cell lymphoblastic leukemia (T-ALL). Transcriptional activation of these oncogenes in leukemic cells typically results from chromosomal rearrangements that place them next to highly active cis-acting transcriptional regulatory elements. However, biallelic activation of TAL1 in some T-ALL cases has been previously proposed. We have used allele-specific mRNA analysis to show that trans-acting mechanisms leading to biallelic overexpression of TAL1 are involved in 10 (42%) of 24 TAL1(+) informative T-ALL cases, 2 (17%) of 12 HOX11(+) informative cases, and 7 (64%) of 11 LMO2(+) informative cases. We propose that aberrant expression of oncogenic transcription factors in a significant fraction of T-ALLs may result from loss of the upstream transcriptional mechanisms that normally down-regulate the expression of these oncogenes during T-cell development. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA USA. Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Dana Farber Canc Inst, Shannon McCormack Adv Mol Diagnost Lab, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630,44 Binney St, Boston, MA 02115 USA. EM thomas_look@dici.harvard.edu FU NCI NIH HHS [CA21765, CA101140, CA21115, CA31946, CA68484, CA92551] NR 10 TC 81 Z9 82 U1 1 U2 5 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 MAR 1 PY 2004 VL 103 IS 5 BP 1909 EP 1911 DI 10.1182/blood-2003-07-2577 PG 3 WC Hematology SC Hematology GA 778NM UT WOS:000189247700057 PM 14604958 ER PT J AU Ito, H Takeuchi, Y Shaffer, J Sykes, M AF Ito, H Takeuchi, Y Shaffer, J Sykes, M TI Local irradiation enhances congenic donor pluripotent hematopoietic stem cell engraftment similarly in irradiated and nonirradiated sites SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; LONG-TERM ENGRAFTMENT; MESSENGER-RNA LEVELS; MIXED CHIMERISM; CONDITIONING REGIMEN; THYMIC IRRADIATION; BODY IRRADIATION; TOLERANCE; INDUCTION; MICE AB Long-term multilineage chimerism is achieved in CD45 congenic mice receiving high bone marrow doses with or without mediastinal irradiation (MI). Increased donor chimerism results in MI-treated compared with nonirradiated animals, suggesting that MI makes "space" for engraftment of donor pluripotent hematopoietic stem cells (PHSCs). We have now examined whether space is systemic or whether increased engraftment of donor marrow in locally irradiated mice is confined to the irradiated bones. While increased donor chimerism was observed in irradiated bones compared with nonirradiated bones of MI-treated animals 4 weeks following bone marrow transplantation (BMT), these differences were minimal by 40 weeks. MI-treated chimeras contained more adoptively transferable donor PHSCs in the marrow of both irradiated and distant bones compared with non-MI-treated chimeras. Similar proportions of donor PHSCs were present in irradiated and nonirradiated bones of locally irradiated mice at both 4 and 40 weeks. Irradiated bones contained more donor short-term repopulating cells than distant bones at 4 weeks, but not 40 weeks, after BMT. Our study suggests that local proliferation of donor PHSCs in mice receiving local irradiation rapidly leads to a systemic increase in donor PHSC engraftment. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp East, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp East, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, 13th St,Bldg 149-5102, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL49915] NR 26 TC 24 Z9 24 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 MAR 1 PY 2004 VL 103 IS 5 BP 1949 EP 1954 DI 10.1182/blood-2003-09-3249 PG 6 WC Hematology SC Hematology GA 778NM UT WOS:000189247700064 PM 14592817 ER PT J AU Ottowitz, WE Dougherty, DD Sirota, AD Niaura, R Rauch, SL Brown, WA AF Ottowitz, WE Dougherty, DD Sirota, AD Niaura, R Rauch, SL Brown, WA TI Cognitive and affective probes of the HPA axis: A SPECT study SO BRAIN AND COGNITION LA English DT Meeting Abstract ID CORTISOL; ACTH C1 Massachusetts Gen Hosp, Psychiat Neurosci Program, Charlestown, MA USA. NR 5 TC 1 Z9 1 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 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR PY 2004 VL 54 IS 2 BP 138 EP 140 PG 3 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 800FT UT WOS:000220015000022 PM 15025037 ER PT J AU Yock, TI Taghian, AG Kachnic, LA Coen, JJ Assaad, SI Powell, SN AF Yock, TI Taghian, AG Kachnic, LA Coen, JJ Assaad, SI Powell, SN TI The effect of delaying radiation therapy for systemic chemotherapy on local-regional control in breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; chemotherapy; local control; radiation therapy ID CONSERVING SURGERY; CONSERVATION THERAPY; EARLY-STAGE; MARGIN STATUS; RECURRENCE; RADIOTHERAPY; RISK; IRRADIATION; LUMPECTOMY; INTERVAL AB Background. It remains controversial as to whether the administration of chemotherapy prior to radiation following the surgical treatment for localized breast cancer compromises local control. Methods. The outcome of 290 patients who received chemotherapy prior to breast or chest wall irradiation following curative breast cancer surgery was retrospectively analyzed to determine if delaying radiation from the time of surgery adversely affects local-regional control. The patients were divided into three groups according to the time interval from definitive surgery to the start of radiation: group 1, < 5 months; group 2, 5 to < 7 months, and group 3, 7+ months. Local-regional and distant failure events were analyzed according to the time delay from surgery to radiation. Results. The median follow-up was 6.0 years ( range, 7 months to 15 years). Loco-regional failure was observed in 22 patients, 18 of which occurred within the original radiation fields. There was no significant adverse effect on local control or distant failure from delaying radiation for systemic chemotherapy. Univariate and multivariate analyses revealed that positive margins after surgery were associated with increased local recurrence. Conclusion. Delaying radiation therapy for greater than 7 months, in order to administer chemotherapy following curative breast cancer surgery, does not compromise local control. However, positive margins were significantly associated with higher rates of local failure and even an increase in radiation boost dose was not able to fully counteract the increased risk of local failure. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox LL, Boston, MA 02114 USA. EM tyock@partners.org NR 28 TC 9 Z9 10 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2004 VL 84 IS 2 BP 161 EP 171 DI 10.1023/B:BREA.0000018414.36274.72 PG 11 WC Oncology SC Oncology GA 780RG UT WOS:000189394700009 PM 14999146 ER PT J AU Diamond, TH Higano, CS Smith, MR Guise, TA Singer, FR AF Diamond, TH Higano, CS Smith, MR Guise, TA Singer, FR TI Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy - Recommendations for diagnosis and therapies SO CANCER LA English DT Review DE bone mineral density; dual-energy X-ray absorptiometry; hypogonadal; hip fracture; lumbar spine; quantitative computed tomography; osteoporosis; prostate carcinoma; androgen deprivation therapy ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; HORMONE AGONISTS; DOUBLE-BLIND; CONTROLLED-TRIAL; ZOLEDRONIC ACID; FRACTURE RISK; HIP FRACTURE; ELDERLY MEN; CANCER AB BACKGROUND. Androgen-deprivation therapy (ADT) is prescribed with increasing frequency for men with prostate carcinoma. There is growing concern about the effects of such therapy on the skeleton. In the current review, the authors addressed the current research, diagnostic methods, and treatment recommendations for bone loss and osteoporosis in men with prostate carcinoma who received ADT. METHODS. Data were obtained from electronic literature searches (for the years 1986 through 2002) and from abstracts and meeting proceedings. All randomized and nonrandomized clinical trials, retrospective studies, and cross-sectional studies of osteoporosis in men with prostate carcinoma who received ADT with or without other therapies were reviewed. RESULTS. The findings confirmed that ADT resulted in significant bone loss in men with prostate carcinoma. Bone mineral density (BMD) of the hip, as measured by dual-energy X-ray absorptiometry (DXA), is considered the preferred site of assessment in older men. Spinal BMD is equally important, although careful interpretation of spinal DXA values is required, because of coexisting facet joint disease and extravertebral calcification. Osteoporosis is diagnosed when BMD is > 2.5 standard deviations below a reference mean. Men with prostate carcinoma who were treated with ADT had average BMD measurements below those of eugonadal men. Rates of bone loss ranged from 2% to 8% in the lumbar spine and from 1.8% to 6.5% in the femoral neck during the initial 12 months of continuous ADT. Retrospective data indicated an increased risk of fracture in men with prostate carcinoma who were treated with ADT. CONCLUSIONS. For men with prostate carcinoma who are at high risk for osteoporosis and fractures, clinical management should be dictated by the results of radiographic and DXA skeletal assessment. (C) 2004 American Cancer Society. C1 Univ New S Wales, Dept Med, Sydney, NSW 2217, Australia. John Wayne Canc Inst, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Dept Clin Med, Los Angeles, CA USA. Univ Virginia, Dept Internal Med, Div Endocrinol, Charlottesville, VA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Seattle Canc Care Alliance, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. RP Diamond, TH (reprint author), Univ New S Wales, Dept Med, St George Hosp Campus, Sydney, NSW 2217, Australia. EM terrydiamond@optushome.com.au NR 63 TC 158 Z9 168 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 892 EP 899 DI 10.1002/cncr.20056 PG 8 WC Oncology SC Oncology GA 775XB UT WOS:000189085000003 PM 14983482 ER PT J AU Barker, FG AF Barker, FG TI Craniotomy for the resection of metastatic brain tumors in the US, 1988-2000 - Decreasing mortality and the effect of provider caseload SO CANCER LA English DT Article DE brain metastasis; craniotomy; mortality; volume-outcome relationship ID STEREOTACTIC RADIOSURGERY; HOSPITAL VOLUME; UNITED-STATES; SURGERY; ANEURYSMS AB BACKGROUND. To assist in selecting treatment for patients with brain metastases, the current study assessed the risk of adverse outcomes after contemporary resection of metastatic brain tumors in relation to patient, surgeon, and hospital characteristics, with particular attention to the volume of care and trends in outcomes. METHODS. A retrospective cohort study of 13,685 admissions from the Nationwide Inpatient Sample between 1988-2000 was performed. Multivariate logistic, ordinal, and loglinear regression were used with endpoints of mortality, discharge disposition, length of stay, and total hospital charges. RESULTS. The overall in-hospital mortality rate was 3.1% and an additional 16.7% of patients were not discharged directly home. In multivariate analyses, larger-volume centers were found to have lower mortality rates for intracranial metastasis resection (odds ratio [OR], 0.79; 95% confidence interval [95% CI], 0.59-1.03 [P = 0.09]). An adverse discharge disposition also was less likely at higher-volume hospitals (OR, 0.75; 95% Cl, 0.65-0.86 [P < 0.001]). For surgeon caseload, mortality was lower with higher-caseload providers (OR, 0.49; 95% Cl, 0.30-0.80 [P 0.004]) and an adverse discharge disposition occurred significantly less frequently (OR, 0.51; 95% Cl, 0.40-0.64 [P < 0.001]). The annual number of resections increased by 79% during the study period, from 3900 (1988) to 7000 (2000). In-hospital mortality rates decreased from 4.6% (1988-1990) to 2.3% (1997-2000), a 49% relative decrease. Length of stay was reported to be significantly shorter with higher-volume providers. Hospital charges were not found to be associated significantly with hospital caseload and were found to be significantly lower after surgery that was performed by higher-caseload surgeons. CONCLUSIONS. The results of the current study found that higher-volume hospitals and surgeons provided superior short-term outcomes after resection of intracranial metastasis was performed, with shorter lengths of stay and a trend toward lower charges. (C) 2004 American Cancer Society. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Div Neurosurg, Boston, MA USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 25 TC 71 Z9 74 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 999 EP 1007 DI 10.1002/cncr.20058 PG 9 WC Oncology SC Oncology GA 775XB UT WOS:000189085000017 PM 14983496 ER PT J AU Clipp, EC Carver, EH Pollak, KI Puleo, E Emmons, KM Onken, J Farraye, FA McBride, CM AF Clipp, EC Carver, EH Pollak, KI Puleo, E Emmons, KM Onken, J Farraye, FA McBride, CM TI Age-related vulnerabilities of older adults with colon adenomas - Evidence from project prevent SO CANCER LA English DT Article DE aging; colorectal carcinoma risk; adenomatous colon polyp; colon adenoma; cancer control ID COLORECTAL-CANCER; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; RISK-FACTORS; DIETARY HEME; RED MEAT; HEALTH; POLYPS; WOMEN; SURVEILLANCE AB BACKGROUND. This report addresses the interface between cancer and aging in the context of colorectal carcinoma (CRC), the second leading cause of cancer death in the U.S. overall and the first leading cause among individuals age 75 years. Because polyp risk increases with age, interventions' to prevent recurrent polyps among older adults likely would reduce CRC morbidity and mortality. METHODS. Data for this study derive from Project Prevent, a multisite, randomized controlled trial designed to reduce behavioral risk factors for CRC among 1247 adults who underwent the removal of greater than or equal to1 adenomatous colon polyps. Middle-aged and older patients were compared on key cognitive-behavioral mechanisms associated with CRC risk and established age-related factors associated with adverse health outcomes. Relations between cognitive-behavioral mechanisms and age-related vulnerability factors identified subgroups of older polyp patients that may have an enhanced risk for CRC. RESULTS. Compared with middle-aged patients, older patients were less concerned about developing CRC, less motivated to reduce their risk, and less confident that their behavior change efforts would succeed. As expected, they also reported more age-related physical, social, and economic vulnerabilities, as expected. Evidence for enhanced CRC risk was found for older patients with multiple comorbid conditions, low social support for change, and perceptions of income inadequacy. CONCLUSIONS. The presence of age-related vulnerability factors may enhance the risk of CRC among older cancer patients by creating barriers to behavioral change. Efforts to reduce the cancer burden in older populations will require attention beyond early detection and surveillance to interventions that account for the unique physical and psychosocial characteristics of older adults. [See editorial on pages 000-000, this issue.] (C) 2004 American Cancer Society. C1 Duke Univ, Med Ctr, Sch Nursing, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC USA. Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Boston Med Ctr, Gastroenterol Sect, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Clipp, EC (reprint author), Duke Univ, Med Ctr, Sch Nursing, Box 3322, Durham, NC 27710 USA. EM clipp003@mc.duke.edu FU NCI NIH HHS [CA81191, R01 CA74000-02]; NIA NIH HHS [AG11268]; NINR NIH HHS [1P20NR07795-01] NR 43 TC 12 Z9 12 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 1085 EP 1094 DI 10.1002/cncr.20082 PG 10 WC Oncology SC Oncology GA 775XB UT WOS:000189085000027 PM 14983506 ER PT J AU Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Shringarpure, R Akiyama, M Hideshima, T Chauhan, D Joseph, M Libermann, TA Garcia-Echeverria, C Pearson, MA Hofmann, F Anderson, KC Kung, AL AF Mitsiades, CS Mitsiades, NS McMullan, CJ Poulaki, V Shringarpure, R Akiyama, M Hideshima, T Chauhan, D Joseph, M Libermann, TA Garcia-Echeverria, C Pearson, MA Hofmann, F Anderson, KC Kung, AL TI Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors SO CANCER CELL LA English DT Article ID NF-KAPPA-B; HISTONE DEACETYLASE INHIBITION; OVERCOMES DRUG-RESISTANCE; ADVANCED PROSTATE-CANCER; LIGAND-INDUCED APOPTOSIS; FACTOR-I RECEPTOR; MOLECULAR SEQUELAE; BIOLOGIC SEQUELAE; CELLS; INTERLEUKIN-6 AB Insulin-like growth factors and their receptor (IGF-1R) have been implicated in cancer pathophysiology. We demonstrate that IGF-1R is universally expressed in various hematologic (multiple myeloma, lymphoma, leukemia) and solid tumor (breast, prostate, lung, colon, thyroid, renal, adrenal cancer, retinoblastoma, and sarcoma) cells. Specific IGF-1R inhibition with neutralizing antibody, antagonistic peptide, or the selective kinase inhibitor NVP-ADW742 has in vitro activity against diverse tumor cell types (particularly multiple myeloma), even those resistant to conventional therapies, and triggers pleiotropic antiproliferative/proapoptotic molecular sequelae, delineated by global transcriptional and proteomic profiling. NVP-ADW742 monotherapy or its combination with cytotoxic chemotherapy had significant antitumor activity in an orthotopic xenograft MM model, providing in vivo proof of principle for therapeutic use of selective IGF-1R inhibitors in cancer. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Novartis Pharma AG, Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02215 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM constantine-mitsiades@dfci.harvard.edu; francesco.hofmann@pharma.novartis.com; kenneth_anderson@dfci.harvard.edu; andrew_kung@dfci.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Kung, Andrew/0000-0002-9091-488X FU PHS HHS [P0-1 78378, R0-1 50947] NR 45 TC 447 Z9 473 U1 3 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2004 VL 5 IS 3 BP 221 EP 230 DI 10.1016/S1535-6108(04)00050-9 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 807UN UT WOS:000220526500006 PM 15050914 ER PT J AU Graner, E Tang, D Rossi, S Baron, A Migita, T Weinstein, LJ Lechpammer, M Huesken, D Zimmermann, J Signoretti, S Loda, M AF Graner, E Tang, D Rossi, S Baron, A Migita, T Weinstein, LJ Lechpammer, M Huesken, D Zimmermann, J Signoretti, S Loda, M TI The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer SO CANCER CELL LA English DT Article ID N-TERMINAL SEQUENCES; DEUBIQUITINATING ENZYME; PATHWAY; EXPRESSION; PROGRESSION; PROTEINS; DISTINCT; TARGET; TUMOR AB Cellular levels of key regulatory proteins are controlled via ubiquitination and subsequent degradation. Deubiquitinating enzymes or isopeptidases can potentially prevent targeted destruction of protein substrates through deubiquitination prior to proteasomal degradation. However, only one deubiquitinating enzyme to date has been matched to a specific substrate in mammalian cells and shown to functionally modify it. Here we show that the isopeptidase USP2a (ubiquitin-specific protease-2a) interacts with and stabilizes fatty acid synthase (FAS), which is often overexpressed in biologically aggressive human tumors. Further, USP2a is androgen-regulated and overexpressed in prostate cancer, and its functional inactivation results in decreased FAS protein and enhanced apoptosis. Thus, the isopeptidase USP2a plays a critical role in prostate cancer cell survival through FAS stabilization and represents a therapeutic target in prostate cancer. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02155 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02155 USA. Novartis Inst BioMed Res, CH-4002 Basel, Switzerland. RP Loda, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02155 USA. EM massimo_loda@dfci.harvard.edu RI Graner, Edgard/K-4411-2012; OI Rossi, Sabrina/0000-0001-9122-1308 FU PHS HHS [P01, R01] NR 29 TC 164 Z9 174 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2004 VL 5 IS 3 BP 253 EP 261 DI 10.1016/S1535-6108(04)00055-8 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 807UN UT WOS:000220526500009 PM 15050917 ER PT J AU Roumiantsev, S Krause, DS Neumann, CA Dimitri, CA Asiedu, F Cross, NCP Van Etten, RA AF Roumiantsev, S Krause, DS Neumann, CA Dimitri, CA Asiedu, F Cross, NCP Van Etten, RA TI Distinct stem cell myeloproliferative/T lymphoma syndromes induced by ZNF198-FGFR1 and BCR-FGFR1 fusion genes from 8p11 translocations SO CANCER CELL LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; FACTOR RECEPTOR 1; TYROSINE KINASE; TRANSFORMING ACTIVITY; T(6/8) TRANSLOCATION; DISORDER FUSES; MICE; DISEASE AB 8p11 myeloproliferative syndrome (EMS) is a hematopoietic stem cell disorder characterized by myeloid hyperplasia and non-Hodgkin's lymphoma with chromosomal translocations fusing several genes, most commonly ZNF198, to fibroblast growth factor receptor-1 (FGFR1). However, patients with BCR-FGFR1 fusion present with typical chronic myeloid leukemia (CML). We demonstrate that ZNF198-FGFR1 induces EMS-like disease in mice, with myeloproliferation and T lymphoma arising from common multipotential progenitors. Mutation of FGFR1 Tyr766 attenuates both myeloid and lymphoid diseases, identifying phospholipase C-gamma1 as a downstream effector. Bcr-FGFR1 binds Grb2 via Bcr Tyr177 and induces CML-like leukemia in mice, whereas Bcr-FGFR1/Y177F lacks Grb2 binding and causes EMS-like disease. These results implicate different signaling pathways originating from both kinase and fusion partner in the pathogenesis of CML and EMS. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Univ Southampton, Sch Med, Div Human Genet, Southampton SO16 6YD, Hants, England. Salisbury Dist Hosp, Wessex Reg Genet Lab, Salisbury SP2 8BJ, Wilts, England. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM rvanetten@tufts-nemc.org RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555 FU NCI NIH HHS [CA90576, CA105043] NR 37 TC 98 Z9 104 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2004 VL 5 IS 3 BP 287 EP 298 DI 10.1016/S1535-6108(04)00053-4 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 807UN UT WOS:000220526500012 PM 15050920 ER PT J AU Krouse, RS Rosenfeld, KE Grant, M Aziz, N Byock, I Sloan, J Casarett, D AF Krouse, RS Rosenfeld, KE Grant, M Aziz, N Byock, I Sloan, J Casarett, D TI Palliative care research: Issues and opportunities SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID MALIGNANT BOWEL OBSTRUCTION; QUALITY-OF-LIFE; CANCER CARE; GUIDELINES C1 So Arizona Vet Affairs Hlth Care Syst, Dept Surg, Tucson, AZ 85723 USA. Univ Arizona, Tucson, AZ 85721 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. City Hope Natl Med Ctr, Dept Nursing Res & Educ, Duarte, CA 91010 USA. NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Sect Palliat Med, Hanover, NH USA. Mayo Canc Ctr, Stat Unit, Rochester, MN USA. Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. RP Krouse, RS (reprint author), So Arizona Vet Affairs Hlth Care Syst, Dept Surg, Surg Care Line 2-112, Tucson, AZ 85723 USA. EM robert.krouse@med.va.gov NR 17 TC 20 Z9 21 U1 0 U2 0 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 MAR PY 2004 VL 13 IS 3 BP 337 EP 339 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000001 PM 15006905 ER PT J AU Al-Delaimy, WK Cho, EY Chen, WY Colditz, G Willet, WC AF Al-Delaimy, WK Cho, EY Chen, WY Colditz, G Willet, WC TI A prospective study of smoking and risk of breast cancer in young adult women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-RECEPTOR STATUS; CIGARETTE-SMOKING; PASSIVE SMOKING; TOBACCO-SMOKE; CAROTENOIDS; EXPOSURE; ALCOHOL AB Objective: To investigate the association between smoking and invasive breast cancers characterized by their estrogen receptor status in a large prospective study of mainly premenopausal women. Method: 112,844 women aged 25-42 years in 1989 were followed 10 years; questionnaire information on medical illnesses and risk factors was collected biennially and information on diet was collected in 1991 and 1995. During this period of follow-up (1,077,536 person-years), 1009 incident breast cancer cases were documented. Results: In the multivariate-adjusted models, smoking status was not significantly related to overall breast cancer risk: compared with never smokers, the relative risks (RRs) were 1.18 [95% confidence interval (CI) 1.02-1.36] for past smokers and 1.12 (95% CI 0.92-1.37) for current smokers. Increasing duration of smoking before the first pregnancy was associated with a greater risk of breast cancer, although little increase was seen in the highest category: compared with never smokers, RRs were 1.42 (95% CI 1.10-1.83) for 15-19 years of smoking and 1.10 (95% CI 0.80-1.52) for greater than or equal to20 years of smoking (P for trend = 0.01). Smoking was related most strongly to the risk of estrogen receptor-positive breast cancers. For women who had smoked for a 120 years, the RR of estrogen receptor-positive cancer was 1.37 (95% CI 1.07-1.74) and the RR of estrogen receptor-negative cancer was 1.04 (95% CI 0.71-1.53). For smoking before age 15, the RRs were 1.49 (95% Cl 1.03-2.17) for estrogen receptor-positive cancer and 1.19 (95% CI 0.69-2.08) for estrogen receptor-negative cancer. Conclusion: Our results suggest that longer duration of smoking may be related to the risk of estrogen receptor-positive breast cancer but possibly less so for estrogen receptor-negative breast cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Al-Delaimy, WK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM wael@hsph.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU PHS HHS [R01-50385] NR 43 TC 47 Z9 49 U1 1 U2 5 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 MAR PY 2004 VL 13 IS 3 BP 398 EP 404 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000011 PM 15006915 ER PT J AU Hamano, Y Sugimoto, H Soubasakos, MA Kieran, M Olsen, BR Lawler, J Sudhakar, A Kalluri, R AF Hamano, Y Sugimoto, H Soubasakos, MA Kieran, M Olsen, BR Lawler, J Sudhakar, A Kalluri, R TI Thrombospondin-1 associated with tumor microenvironment contributes to low-dose cyclophosphamide-mediated endothelial cell apoptosis and tumor growth suppression SO CANCER RESEARCH LA English DT Article ID BASEMENT-MEMBRANE; ANGIOGENESIS; COLLAGEN; INHIBITOR; CHEMOTHERAPY; MOBILIZATION; EXPRESSION; SURVIVAL; DRUGS; MICE AB Low-dose cyclophosphamide (LDC) induces selective apoptosis of endothelial cells within the vascular bed of tumors. Here, we investigated a hypothesis that the effect of LDC is mediated by the pro-apoptotic action of endogenous inhibitors of angiogenesis. Tumors treated with LDC demonstrate similar expression of matrix metalloproteinases and also basement membrane-derived angiogenesis inhibitors when compared with wild-type tumors, whereas the expression of thrombospondin-1 (TSP-1) is significantly elevated in LDC-treated tumors. We used mice with an absence of type XVIII collagen (endostatin) or type IV collagen alpha3 chain (tumstatin) or TSP-1 to assess the contribution of these endogenous inhibitors of angiogenesis on LDC-mediated tumor suppression. Lack of TSP-1 in the host in addition to tumor cells leads to diminished capacity of LDC to suppress tumor growth, whereas the absence of endostatin and tumstatin did not alter the effect of LDC. LDC treatment predominantly induces selective expression of TSP-1 in tumor cells and peri-vascular cells and facilitates apoptosis of proliferating endothelial cells, with minimal direct effect on tumor cells and peri-vascular cells. These studies indicate that TSP-1 contributes to tumor growth suppression induced by LDC and suggest that tumors that express high basal level of TSP-1 may be more susceptible to tumor suppression by such a regimen. This study also makes a strong case for TSP-1 expression levels as a potential predictive marker for the successful use of LDC in cancer patients. C1 Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med & Canc Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Kalluri, R (reprint author), Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med & Canc Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM rkalluri@bidmc.harvard.edu RI Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NIDDK NIH HHS [DK 55001] NR 30 TC 117 Z9 132 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 MAR 1 PY 2004 VL 64 IS 5 BP 1570 EP 1574 DI 10.1158/0008-5472.CAN-03-3126 PG 5 WC Oncology SC Oncology GA 780DY UT WOS:000189357800002 PM 14996710 ER PT J AU Tung, CH Zeng, Q Shah, K Kim, DE Schellingerhout, D Weissleder, R AF Tung, CH Zeng, Q Shah, K Kim, DE Schellingerhout, D Weissleder, R TI In vivo imaging of beta-galactosidase activity using far red fluorescent switch SO CANCER RESEARCH LA English DT Article ID REPORTER GENE; TUMOR-GROWTH; EXPRESSION; ASSAYS; VECTORS; CANCER; DNA AB beta-Galactosidase (beta-gal) has been widely used as a transgene reporter enzyme, and several substrates are available for its in vitro detection. The ability to image beta-gal expression in living animals would further extend the use of this reporter. Here we show that DDAOG, a conjugate of beta-galactoside and 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) (DDAO), is not only a chromogenic beta-gal substrate but that the cleavage product has far-red fluorescence properties detectable by imaging. Importantly, the cleavage substrate shows a 50-nm red shift, enabling its specific detection in a background of intact probe, a highly desirable feature for in vivo imaging. Specifically, we show that beta-gal-expressing 9L gliomas are readily detectable by red fluorescence imaging in comparison with the native 9L gliomas. We furthermore show that herpes simplex virus amplicon-mediated LacZ gene transfer into tumors can be transiently and thus serially visualized over time. The results indicated that in vivo real-time detection of beta-gal activity is possible by fluorescence imaging technology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA86355, R01 CA99385] NR 22 TC 107 Z9 108 U1 3 U2 30 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 MAR 1 PY 2004 VL 64 IS 5 BP 1579 EP 1583 DI 10.1158/0008-5472.CAN-03-3226 PG 5 WC Oncology SC Oncology GA 780DY UT WOS:000189357800004 PM 14996712 ER PT J AU Liu, JS Yang, G Thompson-Lanza, JA Glassman, A Hayes, K Patterson, A Marquez, RT Auersperg, N Yu, YH Hahn, WC Mills, GB Bast, RC AF Liu, JS Yang, G Thompson-Lanza, JA Glassman, A Hayes, K Patterson, A Marquez, RT Auersperg, N Yu, YH Hahn, WC Mills, GB Bast, RC TI A genetically defined model for human ovarian cancer SO CANCER RESEARCH LA English DT Article ID SURFACE EPITHELIAL-CELLS; NF-KAPPA-B; K-RAS PROTOONCOGENE; GENE-EXPRESSION; TELOMERASE ACTIVITY; SPONTANEOUS TRANSFORMATION; MOUSE MODEL; P53 GENE; IN-VITRO; TUMORS AB Disruptions of the p53, retinoblastoma (Rb), and RAS signaling pathways and activation of human telomerase reverse transcriptase (hTERT) are common in human ovarian cancer; however, their precise role in ovarian cancer development is not clear. We thus introduced the catalytic subunit of hTERT, the SV40 early genomic region, and the oncogenic alleles of human HRAS or KRAS into human ovarian surface epithelial cells and examined the phenotype and gene expression profile of those cells. Disruption of p53 and Rb pathway by SV40 early genomic region and hTERT immortalized but did not transform the cells. Introduction of HRAS(V12) or KRAS(V12) into the immortalized cells, however, allowed them to form s.c. tumors after injection into immunocompromised mice. Peritoneal injection of the transformed cells produced undifferentiated carcinoma or malignant mixed Mullerian tumor and developed ascites; the tumor cells are focally positive for CA125 and mesothelin. Gene expression profile analysis of transformed cells revealed elevated expression of several cytokines, including interleukin (IL)-1beta, IL-6, and IL-8, that are up-regulated by the nuclear factor-kappaB pathway, which is known to contribute to the tumor growth of naturally ovarian cancer cells. Incubation with antibodies to IL-1beta or IL-8 led to apoptosis in the ras-transformed cells and ovarian cancer cells but not in immortalized cells that had not been transformed. Thus, the transformed human ovarian surface epithelial cells recapitulated many features of natural ovarian cancer including a subtype of ovarian cancer histology, formation of ascites, CA125 expression, and nuclear factor-kappaB-mediated cytokine activation. These cells provide a novel model system to study human ovarian cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Unit 85, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. Univ British Columbia, Div Res, Dept Obstet & Gynecol, Vancouver, BC, Canada. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02138 USA. RP Liu, JS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Unit 85, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jliu@mdanderson.org RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 FU NCI NIH HHS [P50 CA83639] NR 64 TC 193 Z9 203 U1 2 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 MAR 1 PY 2004 VL 64 IS 5 BP 1655 EP 1663 DI 10.1158/0008-5472.CAN-03-3380 PG 9 WC Oncology SC Oncology GA 780DY UT WOS:000189357800016 PM 14996724 ER PT J AU Mizukami, Y Li, JN Zhang, XB Zimmer, MA Iliopoulos, O Chung, DC AF Mizukami, Y Li, JN Zhang, XB Zimmer, MA Iliopoulos, O Chung, DC TI Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer SO CANCER RESEARCH LA English DT Article ID TUMOR ANGIOGENESIS; FACTOR EXPRESSION; FACTOR-I; TRANSCRIPTION FACTOR; GENE-TRANSCRIPTION; SIGNALING PATHWAY; RESPONSE ELEMENT; DOWN-REGULATION; FACTOR 1-ALPHA; UP-REGULATION AB The induction of vascular endothelial growth factor (VEGF) is an essential feature of tumor angiogenesis, and the hypoxia-inducible factor-1 (HIF-1) transcription factor is known to be a key mediator of this process. In colon cancer, the frequently mutated K-ras oncogene also can regulate VEGF expression, but the role that K-ras may play in hypoxia is unknown. Hypoxia induced VEGF promoter activity, mRNA, and protein levels in colon cancer cells. Although HIF-1alpha was induced by hypoxia, VEGF reporter constructs with selectively mutated hypoxia-response elements remained responsive to hypoxia. In addition, "knockdown" of HIF-1alpha by RNA interference only minimally inhibited the hypoxic induction of VEGF. A region of the VEGF promoter between -420 and -90 by mediated this HIF-independent induction by hypoxia. The introduction of K-ras(Val12) augmented the hypoxic induction of VEGF, and this was observed in wild-type and HIF-1alpha knockdown colon cancer cells. Thus, VEGF may be induced by hypoxia through HIF-dependent and HIF-independent pathways, and K-ras also can induce VEGF in hypoxia independent of HIF-1. These findings suggest the existence of multiple mechanisms regulating the hypoxic induction of VEGF in colon cancer. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Oncol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-825,50 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu FU NCI NIH HHS [CA92594] NR 51 TC 110 Z9 124 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 MAR 1 PY 2004 VL 64 IS 5 BP 1765 EP 1772 DI 10.1158/0008-5472.CAN-03-3017 PG 8 WC Oncology SC Oncology GA 780DY UT WOS:000189357800030 PM 14996738 ER PT J AU Pold, M Zhu, LX Sharma, S Burdick, MD Lin, Y Lee, PPN Pold, A Luo, J Krysan, K Dohadwala, M Mao, JT Batra, RK Strieter, RM Dubinett, SM AF Pold, M Zhu, LX Sharma, S Burdick, MD Lin, Y Lee, PPN Pold, A Luo, J Krysan, K Dohadwala, M Mao, JT Batra, RK Strieter, RM Dubinett, SM TI Cyclooxygenase-2-dependent expression of angiogenic CXC chemokines ENA-78/CXC ligand (CXCL) 5 and interleukin-8/CXCL8 in human non-small cell lung cancer SO CANCER RESEARCH LA English DT Article ID FACTOR-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER; TUMOR ANGIOGENESIS; PROSTAGLANDIN E-2; MOLECULAR-BIOLOGY; BCL-2 EXPRESSION; FACTOR BETA-1; IN-VIVO; APOPTOSIS AB Elevated tumor cyclooxygenase (COX)-2 activity plays a multifaceted role in non-small cell lung cancer (NSCLC). To elucidate the role of COX-2 in the in vitro and in vivo expression of two known NSCLC angiogenic peptides, CXC ligand (CXCL) 8 and CXCL5, we studied two COX-2 gene-modified NSCLC cell lines, A549 and H157. COX-2 overexpression enhanced the in vitro expression of both CXCL8 and CXCL5. In contrast, specific COX-2 inhibition decreased the production of both peptides as well as nuclear translocation of nuclear factor kappaB. In a severe combined immunodeficient mouse model of human NSCLC, the enhanced tumor growth of COX-2-overexpressing tumors was inhibited by neutralizing anti-CXCL5 and anti-CXCL8 antisera. We conclude that COX-2 contributes to the progression of NSCLC tumorigenesis by enhancing the expression of angiogenic chemokines CXCL8 and CXCL5. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Pulm & Crit Care Med, 37-131 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU NCI NIH HHS [CA87879, P50 CA90388, R01 CA71818, R01 CA85686]; NHLBI NIH HHS [P01 HL67665] NR 76 TC 86 Z9 96 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2004 VL 64 IS 5 BP 1853 EP 1860 DI 10.1158/0008-5472.CAN-03-3262 PG 8 WC Oncology SC Oncology GA 780DY UT WOS:000189357800041 PM 14996749 ER PT J AU Witzke, CF MacNeill, BD Lowe, HC Houser, SL Palacios, IF AF Witzke, CF MacNeill, BD Lowe, HC Houser, SL Palacios, IF TI Coronary in-stent restenosis following beta brachytherapy - A histopathological examination SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE stent; restenosis; brachytherapy; histology ID BALLOON ANGIOPLASTY; PROLIFERATION; ATHERECTOMY; RADIATION; PLACEMENT; TISSUE; MATRIX; TRIAL AB Two cases of in-stent restenosis of a coronary artery bypass vein graft following beta brachytheraphy are presented. Previously unreported histopathology of directed atherectomy specimens of such restenotic lesions and a discussion of their proposed significance form the basis of this report. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Houser, SL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. EM houser.stuart@mgh.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD MAR-APR PY 2004 VL 13 IS 2 BP 85 EP 90 DI 10.1016/s1054-8807(03)00136-4 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 807EA UT WOS:000220483600004 PM 15033157 ER PT J AU Yu, QY Sicinski, P AF Yu, QY Sicinski, P TI Mammalian cell cycles without cyclin E-CDK2 SO CELL CYCLE LA English DT Article DE cyclin E; CDK2; cell cycle; mouse knockout ID HISTONE GENE-TRANSCRIPTION; S-PHASE; DEPENDENT KINASES; DNA-REPLICATION; RETINOBLASTOMA PROTEIN; CENTROSOME DUPLICATION; P300 COACTIVATOR; FREE SYSTEM; G1 CYCLIN; CDK2 AB The family of mammalian E-type cyclins is composed of two proteins, termed cyclin E1 and E2. These two cyclins are widely expressed in proliferating cells. E-cyclins bind and activate cyclin dependent kinase CDK2. Cyclin E-CDK2 complexes were believed to play critical function in driving cell cycle progression of normal, nontransformed cells and of cancer cells. Several recent reports challenge this notion. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Beijing Univ, Beijing Tumor Hosp, Dept Cell Biol, Beijing 100871, Peoples R China. Beijing Univ, Beijing Canc Inst, Beijing 100871, Peoples R China. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [CA83688, CA85296] NR 54 TC 15 Z9 15 U1 1 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR PY 2004 VL 3 IS 3 BP 292 EP 295 PG 4 WC Cell Biology SC Cell Biology GA 833TF UT WOS:000222361400019 PM 14726682 ER PT J AU Matute-Bello, G Winn, RK Martin, TR Liles, WC AF Matute-Bello, G Winn, RK Martin, TR Liles, WC TI Sustained lipopolysaccharide-induced lung inflammation in mice is attenuated by functional deficiency of the Fas/Fas ligand system SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID EPITHELIAL-CELL APOPTOSIS; SOLUBLE FAS LIGAND; CONFER IMMUNE PRIVILEGE; INJURY; EXPRESSION; ACTIVATION; DEATH AB To determine whether the Fas/Fas ligand (FasL) (CD95/CD178) system contributes to the development of an inflammatory response in vivo, 2.5 mug of bacterial lipopolysaccharide (LPS; endotoxin) per g was administered intranasally to healthy mice (C57BL/6) and mutant mice deficient in either Fas (lpr mice) or FasL (g/d mice). Sustained LPS-induced neutrophilic inflammation in the lungs was attenuated in both lpr and gld mice. These observations provide further evidence of a proinflammatory role for the Fas/FasL system in the lungs. C1 Univ Washington, Sch Med, Med Res Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. RP Matute-Bello, G (reprint author), Vet Adm Med Ctr, Pulm Res Grp, 1660 S Columbian Way, Seattle, WA 98108 USA. EM matuteb@u.washington.edu FU NHLBI NIH HHS [HL62995, HL65892, HL70840-01, K08 HL070840, R01 HL062995, R01 HL065892] NR 15 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2004 VL 11 IS 2 BP 358 EP 361 DI 10.1128/CDLI.11.2.358-361.2004 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 807DV UT WOS:000220483100021 PM 15013988 ER PT J AU Kirkwood, JM Manola, J Ibrahim, J Sondak, V Ernstoff, MS Rao, U AF Kirkwood, JM Manola, J Ibrahim, J Sondak, V Ernstoff, MS Rao, U TI A pooled analysis of Eastern Cooperative Oncology Group and Intergroup trials of adjuvant high-dose interferon for melanoma SO CLINICAL CANCER RESEARCH LA English DT Article ID RESECTED MELANOMA AB Purpose: Nearly 2000 patients with stage IIB and III melanoma have participated in four multicenter, randomized trials, conducted by the Eastern Cooperative Oncology Group and the Intergroup, investigating adjuvant high-dose IFN-alpha 2b therapy. The objectives of this study were to update the analyses of each individual trial and to analyze prognostic factors and treatment effects based on pooled data. Experimental Design: Survival and disease status were updated to April 2001. Analysis of prognostic factors using optimized statistical models was based on data from patients in E1684, E1690, E1694, and E2696. Analysis of treatment effects versus observation (Obs) was based on data from 713 patients randomized to high-dose IFN-alpha 2b (HDI) or Ohs in Trials E1684 and E1690. Results: Updated analysis of E1684, E1690, and E1694 confirmed their original conclusions, now at median follow-up intervals of 2.1-12.6 years. Based on two-sided univariate log-rank analysis of pooled data from E1684 and E1690 (median follow-up, 7.2 years), relapse-free survival (RFS)-but not overall survival (OS)-was significantly prolonged (two-sided log-rank P value = 0.006) for patients treated with HDI versus Obs. Among all patients, prognostic factors that significantly negatively impacted RFS and OS included ulceration, recurrent disease at entry, enrollment in E1684, and age > 49 years. Multivariate statistical models adjusting for these factors confirmed the statistically significant RFS benefit of HDI versus Ohs but did not demonstrate a significant OS benefit in the pooled populations. Conclusions: In patients with high-risk resected melanoma, HDI is effective adjuvant therapy with strong evidence for improved RFS and evidence for moderate improvement in OS based on two prospective randomized studies but not the pooled analysis. Analyses of predictors of relapse and response are now needed to improve the therapeutic value of this modality. C1 Dartmouth Hitchcock Med Ctr, Dept Med, Div Hematol Oncol, Lebanon, NH 03766 USA. Univ Michigan, Dept Surg, Div Surg Oncol, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Dept Med, Med Ctr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Melanoma Ctr, Dept Pathol, Pittsburgh, PA USA. RP Kirkwood, JM (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Med Ctr, Res Pavil,Suite 1-32,5114 Ctr Ave, Pittsburgh, PA 15213 USA. EM kirkwoodjm@msx.upmc.edu FU NCI NIH HHS [CA-23318] NR 8 TC 284 Z9 298 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 MAR 1 PY 2004 VL 10 IS 5 BP 1670 EP 1677 DI 10.1158/1078-0432.CCR-1103-3 PG 8 WC Oncology SC Oncology GA 801IH UT WOS:000220089100017 PM 15014018 ER PT J AU Laposata, M AF Laposata, M TI Patient-specific narrative interpretations of complex clinical laboratory evaluations: Who is competent to provide them? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM mlaposata@partners.org NR 12 TC 31 Z9 32 U1 0 U2 1 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 MAR PY 2004 VL 50 IS 3 BP 471 EP 472 DI 10.1373/clinchem.2003.028951 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 779GT UT WOS:000189287500004 PM 14981026 ER PT J AU Kuo, A Dienstag, JL Chung, RT AF Kuo, Alexander Dienstag, Jules L. Chung, Raymond T. TI Tenofovir Disoproxil Fumarate for the Treatment of Lamivudine-Resistant Hepatitis B SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: Lamivudine resistance occurs in patients with chronic hepatitis B at rates of 16%-32% after 1 year and 49% after 3years. Adefovir dipivoxil, a nucleotide analogue recently approved by the Food and Drug Administration for the treatment of chronic hepatitis B, is effective against hepatitis B virus (HBV) but has been associated with renal toxicity at high doses. Tenofovir disoproxil fumarate is another nucleotide analogue with demonstrated antiviral activity against both wildtype and lamivudine-resistant HBV. Tenofovir, at its licensed dose, has not been associated with renal dysfunction. Methods: We describe a series of 9 patients with lamivudine-resistant hepatitis B treated with tenofovir, 300 mg, once daily before the availability of adefovir. Levels of HBV DNA, alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg), and antibody to HBeAg (anti-HBe) were monitored. Results: The addition of tenofovir to the existing regimen of lamivudine resulted in a median decline of 4.5 log(10) copies/mL in HBV DNA levels (range, 3.2-6.3 log(10) copies/mL) after a median treatment duration of 12 months (range, 6-16 mo). HBeAg seroconversion was observed in 2 patients, with a third patient undergoing HBeAg loss while remaining anti-HBe negative. In 4 of 7 patients with elevated ALT levels at baseline, ALT levels normalized. No significant adverse events were encountered during treatment. Conclusions: In patients with lamivudine-resistant hepatitis B, treatment with tenofovir is well tolerated and results in significant virological, serological, and biochemical improvements on par with those seen with high-dose adefovir (30 mg/day) therapy, without the complication of renal toxicity. C1 [Dienstag, Jules L.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Kuo, Alexander] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Dienstag, Jules L.; Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Jackson 825, Boston, MA 02114 USA. EM rtchung@partners.org NR 24 TC 73 Z9 76 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2004 VL 2 IS 3 BP 266 EP 272 DI 10.1053/S1542-3565(04)00017-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KO UT WOS:000208071500012 PM 15017612 ER PT J AU Neuzil, KM AF Neuzil, KM TI Influenza vaccine for children SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CONTROLLED TRIAL; EFFICACY; DISEASE C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Neuzil, KM (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, 1660 S Columbian Wy, Seattle, WA 98108 USA. EM kneuzil@u.washington.edu NR 11 TC 4 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2004 VL 38 IS 5 BP 689 EP 691 DI 10.1086/382888 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 777EY UT WOS:000189163900012 PM 14986253 ER PT J AU Ali, T Scott, N Kallas, W Halliwell, ME Savino, C Rosenberg, E Ferraro, M Hohmann, E AF Ali, T Scott, N Kallas, W Halliwell, ME Savino, C Rosenberg, E Ferraro, M Hohmann, E TI Detection of influenza antigen with rapid antibody-based tests after intranasal influenza vaccination (FluMist) SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID A VIRUS; ENZYME-IMMUNOASSAY; FLU; ADULTS; LIVE AB Rapid tests for influenza antigen detection are frequently used, but it is not known how receipt of intranasal influenza vaccine affects results of these tests. We tested healthy adults who received either intranasal or intramuscular influenza vaccine. Of the 14 intranasal vaccine recipients, 7 (50%) had a direct fluorescent antibody test (DFA) result and 2 (14%) had an enzyme immunoassay (EIA) result that was positive for influenza antigen within 7 days after vaccination. No subjects had positive EIA results on day 12 or 13 after vaccination. For some intranasal vaccine recipients, rapid influenza-antigen detection tests yield positive results within 1 week after vaccination. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Microbiol Labs, Boston, MA 02114 USA. RP Hohmann, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM ehohmann@partners.org FU NIAID NIH HHS [AI51206] NR 10 TC 15 Z9 21 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2004 VL 38 IS 5 BP 760 EP 762 DI 10.1086/382887 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 777EY UT WOS:000189163900023 PM 14986264 ER PT J AU Clapp, L Martin, B Beresford, TP AF Clapp, L Martin, B Beresford, TP TI Sublingual cocaine - Novel recurrence of an ancient practice SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE cocaine; sublingual; routes of use ID VALIDITY AB Present knowledge suggests that cocaine is almost always used by snorting, injecting, or smoking. During a recent treatment study, we encountered 2 cases who reported active cocaine use by the sublingual route exclusively. We describe here 1) the method of sublingual use, 2) its attraction for cocaine dependent individuals, especially those who wish to conceal use, and 3) concerns regarding the medical consequences of sublingual cocaine use. Sublingual cocaine use may cause unique medical symptoms and may easily evade detection by medical personnel. C1 Dept Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. RP Beresford, TP (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. EM Thomas.Beresford@uchsc.edu NR 7 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD MAR-APR PY 2004 VL 27 IS 2 BP 93 EP 94 DI 10.1097/00002826-200403000-00010 PG 2 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 817YU UT WOS:000221213600010 PM 15252272 ER PT J AU Bozic, KJ Rubash, HE AF Bozic, KJ Rubash, HE TI The painful total hip replacement SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ERYTHROCYTE SEDIMENTATION-RATE; C-REACTIVE PROTEIN; BONE SCANS; ARTHROPLASTY; PROSTHESIS; TECHNETIUM; ASPIRATION; INFECTION; OSTEOARTHRITIS; ARTHROGRAPHY AB Total hip replacement is one of the most common and successful orthopaedic procedures. However, evaluation and treatment of the painful total hip replacement is one of the most difficult challenges for the arthroplasty surgeon. The differential diagnosis includes causes that are intrinsic and extrinsic to the hip. A thorough history and physical examination provide the basis for a focused, efficient workup of the painful total hip replacement. The temporal onset, duration, severity, site, and character of the pain all provide important clues in determining the cause of the painful total hip replacement. The physical examination should focus on tests and maneuvers that reproduce the patient's symptoms. Laboratory tests and radiographic evaluation are used selectively as indicated by the history and physical examination findings. With a careful and thorough evaluation, the cause of the painful total hip replacement can be determined in most patients, and the appropriate treatment can be initiated. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM bozick@orthosurg.ucsf.edu NR 46 TC 36 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2004 IS 420 BP 18 EP 25 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 808PE UT WOS:000220580200004 PM 15057074 ER PT J AU Bozic, KJ Freiberg, AA Harris, WH AF Bozic, KJ Freiberg, AA Harris, WH TI The high hip center SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FOLLOW-UP; ACETABULAR COMPONENT; FEMORAL-HEAD; REVISION ARTHROPLASTY; RHEUMATOID-ARTHRITIS; SUPERIOR PLACEMENT; RECONSTRUCTION; REPLACEMENT; DISLOCATION; ALLOGRAFTS AB Revision of a failed acetabular component presents many challenges to the arthroplasty surgeon. The goal in most cases should be to reconstruct the acetabulum by positioning the hip center as close as possible to the anatomic hip center. However, severe acetabular bone stock deficiency and distorted acetabular anatomy often preclude placement of the acetabular component at the true anatomic hip center. In these cases, many options exist for reconstruction of the acetabulum, including placement of the cup superiorly at a high hip center. Although biomechanical studies have shown that superolateral placement of the hip center may lead to increased moments and forces across the hip (leading to potentially higher rates of loosening), superior only displacement of the hip center does not seem to adversely affect the forces about the hip. Proximal placement of the hip center facilitates contact between intact, viable host bone and the acetabular implant, thereby reducing the need for structural bone grafts, and increasing the chances for stable bony ingrowth. With proper patient selection and meticulous surgical technique, the high hip center can be a useful technique for reconstruction of the deficient acetabulum in the patient with a loose acetabular component after total hip arthroplasty. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Hip & Implant Unit, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. EM bozick@orthosurg.ucsf.edu NR 29 TC 18 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2004 IS 420 BP 101 EP 105 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 808PE UT WOS:000220580200014 PM 15057084 ER PT J AU Zeegen, EN Aponte-Tinao, LA Hornicek, FJ Gebhardt, MC Mankin, HJ AF Zeegen, EN Aponte-Tinao, LA Hornicek, FJ Gebhardt, MC Mankin, HJ TI Survivorship analysis of 141 modular metallic endoprostheses at early followup SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID KINEMATIC ROTATING HINGE; PRIMARY OSTEOGENIC-SARCOMA; HIGH-GRADE OSTEOSARCOMA; ADJUVANT CHEMOTHERAPY; LIMB SALVAGE; PREOPERATIVE CHEMOTHERAPY; MUSCULOSKELETAL SARCOMA; MALIGNANT-TUMORS; EWINGS-SARCOMA; BONE-TUMORS AB Although our institution historically has been known for its use of osteoarticular allografts in limb salvage surgery for tumors, during the last 8 years there has been an increase in the use of metallic modular endoprostheses. A retrospective review of 141 patients in whom a modular endoprosthesis was implanted in the past 8 years was done, and survival data were compiled using Kaplan-Meier survival analysis, clinical score was determined using a previously described system, and a multivariate regression analysis was done to identify independent risk factors. There were 13 failures (defined as need for revision of the majority of the prosthetic components, excluding cases of local recurrence) yielding an overall implant survival of 91%. Based on Kaplan-Meier estimates, the endoprosthetic survival rate was 88% at 3 years and 76% at 5 years; per location, it was 100% for the proximal humerus, 100% for the proximal femur, 87% for modular knees, and 53% for total femoral implants at 3 years. The clinical scores were good to excellent in 74% of the patients. Multivariate analysis showed that only location and infection were independent risk factors for prosthesis failure. Loosening, infection, and dislocation were independently predictive of a fair or poor clinical score. Age, gender, diagnosis, length of implant, dislocation, nor failed prior allograft had an independent effect on implant survival or clinical outcome. The proximal humeral and proximal femoral implants had greater survival rates than modular knee and total femoral implants. Conversion of failed allografts to modular endoprostheses had a trend for a higher failure rate, but after a multivariate analysis, did not prove to be an independent risk factor for failure. We think that our experience is similar to other endoprosthesis survivorship reports in the literature with short-term followup. C1 Massachusetts Gen Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Zeegen, EN (reprint author), Univ Calif Los Angeles, Dept Orthopaed Surg, 10833 Conte Ave,Room 76-143,CHS, Los Angeles, CA 90025 USA. EM ezeegen_00@yahoo.com NR 44 TC 84 Z9 100 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAR PY 2004 IS 420 BP 239 EP 250 DI 10.1097/01.blo.0000126224.97525.5b PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 808PE UT WOS:000220580200034 PM 15057104 ER PT J AU Cohen, LS Nonacs, R Viguera, AC Reminick, A AF Cohen, LS Nonacs, R Viguera, AC Reminick, A TI Diagnosis and treatment of depression during pregnancy SO CNS SPECTRUMS LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; PAROXETINE WITHDRAWAL SYNDROME; EXPOSED IN-UTERO; PANIC DISORDER; RECURRENT DEPRESSION; ELECTROCONVULSIVE-THERAPY; TRICYCLIC ANTIDEPRESSANTS; MATERNAL CLOMIPRAMINE; PRENATAL EXPOSURE; BIRTH OUTCOMES AB Pregnancy has frequently been described as a time of affective well-being. However, a growing literature suggests that women are neither "protected" against new-onset or recurrence of depression during this time. Diagnosis and effective treatment of depression during pregnancy requires a careful weighing of risk of treatment which may include psychotropic medications against the risks associated with failure to adequately manage affective distress and its potential impact of maternal and fetal well-being. Treatment options during pregnancy are reviewed in the context of developing the most appropriate risk/benefit decision for individual patients with past or current depression who either anticipate pregnancy or who become pregnant. CNS Spectr. 2004;9(3):209-216 C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, WACC Bldg,Room 815,15 Parkman St, Boston, MA 02114 USA. EM lcohen2@partners.org FU NIMH NIH HHS [K23 MH 1609] NR 86 TC 21 Z9 22 U1 1 U2 4 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2004 VL 9 IS 3 BP 209 EP 216 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VB UT WOS:000226890800007 PM 14999161 ER PT J AU Deckersbach, T Perlis, RH Frankle, G Gray, SM Grandin, L Dougherty, DD Nierenberg, AA Sachs, GS AF Deckersbach, T Perlis, RH Frankle, G Gray, SM Grandin, L Dougherty, DD Nierenberg, AA Sachs, GS TI Presence of irritability during depressive episodes in bipolar disorder SO CNS SPECTRUMS LA English DT Article ID MIXED STATES; MANIA; SYMPTOMS; ANGER AB Background: This study examined the prevalence of irritability in patients with bipolar I disorder during an episode of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) major depression who do not meet criteria for a mixed episode. Method: A chart review of 111 patients with bipolar I disorder treated at the Massachusetts General Hospital Bipolar Clinic between 1998 and 2000 identified 34 patients who met criteria for a DSM-IV major depressive episode in the absence of (1) mood elevation and/or (2) irritability associated with any additional above threshold DSM-IV symptoms of mania. Data gathered from the charts utilized prospective ratings made routinely at each clinic visit using the Clinical Monitoring Form (CMF), a structured assessment instrument which includes modified versions of the mood modules of the Structured Clinical Interview for DSM-IV. Data from these 34 patients were reviewed to determine the presence of irritability. Results: The frequency of abnormal irritability in these 34 patients followed a bimodal distribution: 26% of the patients showed abnormal irritability greater than or equal to75% of the time, compared with 68% of the patients with abnormal irritability less than or equal to30% of the time. Of the high-irritability patients, psychomotor agitation was rated as definitely present to a significant degree in 44%. Talkativeness and distractibility were rated present but subthreshold in one patient each. All other symptoms of DSM-IV mania were absent. Conclusion: Approximately 25% of patients with bipolar I disorder who meet criteria for a DSM-IV major depressive episode also experienced substantial irritability in the absence of associated symptoms of mania. Our results suggest that abnormal irritability is not limited to mania or mixed states. CNS Spectr. 2004;9(3):227-231 C1 Harvard Univ, Sch Med, Dept Psychiat, Harvard Bipolar Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Psychiat Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Deckersbach, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Bipolar Res Program, 149-2611,149,13th St, Charlestown, MA 02129 USA. EM tdeckersbachg@partners.org NR 17 TC 24 Z9 25 U1 1 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD MAR PY 2004 VL 9 IS 3 BP 227 EP 231 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895VB UT WOS:000226890800009 PM 14999163 ER PT J AU Gupta, V Harkin, DP Kawakubo, H Maheswaran, S AF Gupta, V Harkin, DP Kawakubo, H Maheswaran, S TI Transforming growth factor-beta superfamily: Evaluation as breast cancer biomarkers and preventive agents SO CURRENT CANCER DRUG TARGETS LA English DT Review ID MULLERIAN-INHIBITING SUBSTANCE; MAMMARY-GLAND DEVELOPMENT; BONE MORPHOGENETIC PROTEIN-2; HORMONE-RELATED PROTEIN; HUMAN SOLID TUMORS; RECEPTOR SUPPRESSES TUMORIGENICITY; RECOMBINANT SOLUBLE BETAGLYCAN; ENDOGLIN MONOCLONAL-ANTIBODIES; VASCULAR ENDOTHELIAL-CELLS; TGF-BETA AB The Transforming Growth Factor-beta (TGFbeta) superfamily of cytokines is comprised of a number of structurally-related, secreted polypeptides that regulate a multitude of cellular processes including proliferation, differentiation and neoplastic transformation. These growth regulatory molecules induce ligand-mediated hetero-oligomerization of distinct type II and type I serine/threonine kinase receptors that transmit signals predominantly through receptor-activated Smad proteins but also induce Smad-independent pathways. Ligands, receptors and intracellular mediators of signaling initiated by members of the TGFbeta family are expressed in the mammary gland and disruption of these pathways may contribute to the development and progression of human breast cancer. Since many facets of TGFbeta and breast cancer have been recently reviewed in several articles, except for discussion of recent developments on some aspects of TGFbeta, the major focus of this review will be on the role of activins, inhibins, BMPs, nodal and MIS-signaling in breast cancer with emphasis on their utility as potential diagnostic, prognostic and therapeutic targets. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Queens Univ Belfast, Dept Oncol, Belfast BT7 1NN, Antrim, North Ireland. RP Gupta, V (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, WRN1024,55 Fruit St, Boston, MA 02114 USA. EM maheswaran@helix.mgh.harvard.edu FU NCI NIH HHS [CA89138-01A1] NR 155 TC 9 Z9 9 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD MAR PY 2004 VL 4 IS 2 BP 165 EP 182 DI 10.2174/1568009043481542 PG 18 WC Oncology SC Oncology GA 833UB UT WOS:000222364000004 PM 15032667 ER PT J AU Post, DE Fulci, G Chiocca, EA Van Meir, EG AF Post, DE Fulci, G Chiocca, EA Van Meir, EG TI Replicative oncolytic herpes simplex viruses in combination cancer therapies SO CURRENT GENE THERAPY LA English DT Review DE gene therapy; tumors; oncolytic virus; herpes simplex virus 1; radiation; chemotherapy ID DIFFUSE LIVER METASTASES; THYMIDINE KINASE GENE; SQUAMOUS-CELL CARCINOMA; HIGH-GRADE GLIOMAS; IONIZING-RADIATION; ANTITUMOR EFFICACY; RIBONUCLEOTIDE REDUCTASE; PROSTATE-CANCER; VECTOR G207; SIGNALING PATHWAY AB Viruses that kill the host cell during their replication cycle have attracted much interest for the specific killing of tumor cells and this oncolytic virotherapy is being evaluated in clinical trials. The rationale for using replicative oncolytic viruses is that viral replication in infected tumor cells will permit in situ viral multiplication and spread of viral infection throughout the tumor mass thus overcoming the delivery problems of gene therapy. Improved understanding of the life cycle of viruses has evidenced multiple interactions between viral and cellular gene products, which have evolved to maximize the ability of viruses to infect and multiply within cells. Differences in viral-cell interactions between normal and tumor cells have emerged that have led to the design of a number of genetically engineered viral vectors that selectively kill tumor cells while sparing normal cells. These viruses have undergone further modifications to carry adjunct therapy genes to increase their anti-cancer abilities. Since these viruses kill cells by oncolytic mechanisms differing from standard anticancer therapies, there is an opportunity that synergistic interactions with other therapies might be found with the use of combination therapy. In this review, we focus on the oncolytic Herpes Simplex Virus-1 (HSV-1) vectors that have been examined in preclinical and clinical cancer models and their use in combination with chemo-, radio-, and gene therapies. C1 Emory Univ, Sch Med, Mol Neurooncol Lab, Dept Neurosurg, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Mol Neurooncol Lab, Dept Hematol Oncol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Mol Neurooncol Labs, Boston, MA 02129 USA. RP Post, DE (reprint author), Emory Univ, Sch Med, Mol Neurooncol Lab, Dept Neurosurg, Atlanta, GA 30322 USA. EM dephelp@emory.edu; evanmei@emory.edu FU NCI NIH HHS [CA87830]; NINDS NIH HHS [NS41403] NR 80 TC 46 Z9 50 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD MAR PY 2004 VL 4 IS 1 BP 41 EP 51 DI 10.2174/1566523044577988 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 863LB UT WOS:000224562100004 PM 15032613 ER PT J AU Saund, MS Demetri, GD Ashley, SW AF Saund, MS Demetri, GD Ashley, SW TI Gastrointestinal stromal tumors (GISTs) SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE gastrointestinal stromal tumor; GIST; KIT; imatinib mesylate; PET scan ID IMATINIB MESYLATE; EMISSION-TOMOGRAPHY; PROGNOSTIC VALUE; SOFT-TISSUE; C-KIT; EXPRESSION; ST1571; REAPPRAISAL; DIAGNOSIS; MUTATIONS AB Purpose of review Gastrointestinal stromal tumors (GISTs) have recently been the subject of considerable clinical and experimental interest. This focus is based on the recognition that GISTs characteristically have uncontrolled activation of the KIT protein, a transmembrane tyrosine kinase receptor involved in cell survival, development, and proliferation. The clinical application of imatinib mesylate, a selective inhibitor of the KIT kinase activity, has provided a novel molecularly targeted therapy for these tumors. This review summarizes publications from the last year regarding these tumors. Recent findings Recent studies have focused on imaging, the identification of prognostic factors and molecular events, and the role of systemic therapy in the treatment of these tumors. Emerging data suggest that the combination of endoscopic ultrasound and fine-needle aspiration analysis for KIT expression may be useful in separating these lesions from other submucosal lesions of the gastrointestinal tract. The benefits and limitations of computed tomography and positron emission tomography in identifying, staging, and evaluating the response to therapy of these lesions have been more clearly defined. Although tumor size and the number of mitoses remain the best prognostic markers, several studies reported provocative data using other markers such as Ki-67, p53, and alterations in p 16(INK4). Mutational analysis of the KIT oncoprotein continues to be the subject of considerable interest in relation to both prognosis and resistance to therapy. Finally, a series of new studies have confirmed the benefits and better defined the results of therapy with imatinib mesylate. There is increasing interest in expanding the role of this agent into the adjuvant setting and in combining such therapy with reoperation for responsive disease. Summary In the past year there have been significant developments in our understanding of GISTs and their response to therapy. Many questions remain unanswered and new issues have arisen as the benefits of imatinib mesylate therapy are revealed. There is considerable optimism that the targeted molecular approach being applied to the treatment of GISTs will serve as a model for the development of similar approaches to other more common tumors. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Ashley, SW (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM sashley@partners.org NR 37 TC 17 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD MAR PY 2004 VL 20 IS 2 BP 89 EP 94 DI 10.1097/00001574-200403000-00007 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 779UF UT WOS:000189319200006 PM 15703627 ER PT J AU Jacobsen, E Freedman, A AF Jacobsen, E Freedman, A TI An update on the role of high-dose therapy with autologous or allogeneic stem cell transplantation in mantle cell lymphoma SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE mantle cell lymphoma; allogeneic stem cell transplant; autologous stem cell transplant; radioimmunotherapy; in vivo purging ID BONE-MARROW-TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; NON-HODGKINS-LYMPHOMAS; LONG-TERM REMISSION; PROGNOSTIC-FACTORS; SEQUENTIAL CHEMOTHERAPY; MOLECULAR REMISSIONS; INTENSIVE THERAPY; NATURAL-HISTORY; FOLLOW-UP AB Purpose of review Early trials of high-dose therapy with autologous stem cell transplantation in mantle cell lymphoma were discouraging, with no clear survival advantage attributable to the procedure. Most early series were plagued by small numbers, retrospective designs, and short follow-up. Also, until recently, allogeneic stem cell transplantation was not an option for most mantle cell lymphoma patients who were too old or infirm to tolerate standard conditioning regimens. Recent findings New advances in allogeneic transplantation, particularly reduced-intensity conditioning regimens, have increased the availability of this procedure to patients with mantle cell lymphoma. New evidence has emerged during the last several years that suggests autologous stem cell transplantation in first complete remission may provide a survival advantage over conventional chemotherapy in patients with mantle cell lymphoma. Additionally, investigational strategies such as in vivo purging with rituximab and the use of radioimmunotherapy in conditioning regimens may further increase response rates and, hopefully, survival in mantle cell lymphoma patients. Finally, recent studies suggest the existence of a graft-versus-lymphoma effect in mantle cell lymphoma providing strong scientific rationale for the possible curative potential of allogeneic stem cell transplantation in this disease. Summary This review focuses on recent advances in allogeneic and autologous transplantation for mantle cell lymphoma. Particular emphasis is placed on the role of autologous transplantation in first complete remission, the role of in vivo purging with rituximab, the utility of radioimmunotherapy and, finally, the evolving strategy of reduced-intensity allogeneic stem cell transplantation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Freedman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM arnold_freedman@dfci.harvard.edu NR 43 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD MAR PY 2004 VL 16 IS 2 BP 106 EP 113 DI 10.1097/00001622-200403000-00004 PG 8 WC Oncology SC Oncology GA 806TU UT WOS:000220457000003 PM 15075900 ER PT J AU Sado, T Okano, M Li, E Sasaki, H AF Sado, T Okano, M Li, E Sasaki, H TI De novo DNA methylation is dispensable for the initiation and propagation of X chromosome inactivation SO DEVELOPMENT LA English DT Article DE X chromosome inactivation; De novo DNA methyltransferases; Xist ID HISTONE METHYLTRANSFERASE ACTIVITY; H3 LYSINE-27 METHYLATION; MOUSE DEVELOPMENT; XIST EXPRESSION; FUNCTIONAL-CHARACTERIZATION; EMBRYONIC STEM; GENE; CELLS; TSIX; ENHANCER AB Xist (X-inactive specific transcript) plays a crucial role in X-inactivation. This non-coding RNA becomes upregulated on the X chromosome that is to be inactivated upon differentiation. Previous studies have revealed that although maintenance-type DNA methyllation is not essential for X-inactivation to occur, it is required for the stable repression of Xist in differentiated cells. However, it is unknown whether differential de novo methyllation at the Xist promoter, which is mediated by Dnmt3a and/or Dnmt3b, is a cause or a consequence of monoallelic expression of Xist. We show that Xist expression is appropriately regulated in the absence of Dnmt3a and Dnmt3b and that a single X chromosome undergoes proper inactivation in mutant females. Our results indicate that a mechanism(s) other than DNA methylation plays a principal role in initiating X-inactivation. We also demonstrate that delayed upregulation of Xist does not induce X-inactivation, consistent with a crucial developmental window for the chromosomal silencing. C1 Natl Inst Genet, Div Human Genet, Mishima, Shizuoka 4118540, Japan. PRESTO, Japan Sci & Technol Agcy, Saitama, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Sado, T (reprint author), Natl Inst Genet, Div Human Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan. EM tsado@lab.nig.ac.jp FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 48 TC 70 Z9 74 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2004 VL 131 IS 5 BP 975 EP 982 DI 10.1242/dev.00995 PG 8 WC Developmental Biology SC Developmental Biology GA 805HS UT WOS:000220358000002 PM 14973270 ER PT J AU Long, FX Chung, UI Ohba, S McMahon, J Kronenberg, HM McMahon, AP AF Long, FX Chung, UI Ohba, S McMahon, J Kronenberg, HM McMahon, AP TI Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton SO DEVELOPMENT LA English DT Article DE osteoblast; endochondral skeleton; chondrocyte; Ihh; Smo ID HORMONE-RELATED PEPTIDE; INDIAN-HEDGEHOG; SONIC-HEDGEHOG; BONE-FORMATION; CARTILAGE DIFFERENTIATION; TRANSGENIC MICE; RECEPTOR; EXPRESSION; PROLIFERATION; PROTEIN AB Indian hedgehog (Ihh) is indispensable for development of the osteoblast lineage in the endochondral skeleton. In order to determine whether Ihh is directly required for osteoblast differentiation, we have genetically manipulated smoothened (Smo), which encodes a transmembrane protein that is essential for transducing all Hedgehog (Hh) signals. Removal of Smo from perichondrial cells by the Cre-LoxP approach prevents formation of a normal bone collar and also abolishes development of the primary spongiosa. Analysis of chimeric embryos composed of wildtype and Smo(n/n) cells indicates that Smo(n/n) cells fail to contribute to osteoblasts in either the bone collar or the primary spongiosa but generate ectopic chondrocytes. In order to assess whether Ihh is sufficient to induce bone formation in vivo, we have analyzed the bone collar in the long bones of embryos in which Ihh was artificially expressed in all chondrocytes by the UAS-GAL4 bigenic system. Although ectopic Ihh does not induce overt ossification along the entire cartilage anlage, it promotes progression of the bone collar toward the epiphysis, suggesting a synergistic effect between ectopic Ihh and endogenous factors such as the bone morphogenetic proteins (BMPs). In keeping with this model, Hh signaling is further found to be required in BMP-induced osteogenesis in cultures of a limb-bud cell line. Taken together, these results demonstrate that Ihh signaling is directly required for the osteoblast lineage in the developing long bones and that Ihh functions in conjunction with other factors such as BMPs to induce osteoblast differentiation. We suggest that Ihh acts in vivo on a potential progenitor cell to promote osteoblast and prevent chondrocyte differentiation. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Tokyo, Sch Med, Dept Bone & Cartilage Regenerat Med, Tokyo, Japan. RP McMahon, AP (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM amcmahon@mcb.harvard.edu FU NIDDK NIH HHS [P01 DK 56246]; NIGMS NIH HHS [GM19621] NR 32 TC 214 Z9 228 U1 1 U2 8 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 MAR PY 2004 VL 131 IS 6 BP 1309 EP 1318 DI 10.1242/dev.01006 PG 10 WC Developmental Biology SC Developmental Biology GA 810FL UT WOS:000220690100011 PM 14973297 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI Twist genes regulate Runx2 and bone formation SO DEVELOPMENTAL CELL LA English DT Editorial Material ID OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; CBFA1 AB Runx2, a master regulator of osteoblast differentiation, is expressed several days before osteoblast genes in bone anlage. In this issue of Developmental Cell, Bialek et al. (2004) show that Twist-1 and Twist-2 suppress the activity of Runx2 and thereby regulate bone formation. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. NR 11 TC 23 Z9 23 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR PY 2004 VL 6 IS 3 BP 317 EP 318 DI 10.1016/S1534-5807(04)00069-3 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834WZ UT WOS:000222442900005 PM 15030754 ER PT J AU Ernst, P Fisher, JK Avery, W Wade, S Foy, D Korsmeyer, SJ AF Ernst, P Fisher, JK Avery, W Wade, S Foy, D Korsmeyer, SJ TI Definitive hematopoiesis requires the mixed-lineage leukemia gene SO DEVELOPMENTAL CELL LA English DT Article ID FETAL LIVER HEMATOPOIESIS; YOLK-SAC HEMATOPOIESIS; MLL-MUTANT MICE; STEM-CELLS; MOUSE EMBRYO; TRANSCRIPTION FACTOR; MAMMALIAN TRITHORAX; HOMEOBOX GENES; IN-VITRO; EXPRESSION AB The Mixed-Lineage Leukemia (MLL) gene encodes a Trithorax-related chromatin-modifying protooncogene that positively regulates Hox genes. In addition to their well-characterized roles in axial patterning, Trithorax and Polycomb family proteins perform less-understood functions in vertebrate hematopoiesis. To define the role of MILL in the development of the hematopoietic system, we examined the potential of cells lacking MILL. MII-deficient cells could not develop into lymphocytes in adult RAG-2 chimeric animals. Similarly, in vitro differentiation of B cells required MLL. In chimeric embryos, MII-deficient cells failed to contribute to fetal liver hematopoietic stem cell/progenitor populations. Moreover, we show that aorta-gonad-mesonephros (AGM) cells from MII-deficient embryos lacked hematopoietic stem cell [HSC) activity despite their ability to generate hematopoietic progeny in vitro. These results demonstrate an intrinsic requirement for MILL in definitive hematopoiesis, where it is essential for the generation of HSCs in the embryo. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Genet, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu FU NCI NIH HHS [P01 CA68484] NR 41 TC 143 Z9 146 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR PY 2004 VL 6 IS 3 BP 437 EP 443 DI 10.1016/S1534-5807(04)00061-9 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 834WZ UT WOS:000222442900016 PM 15030765 ER PT J AU Doyle, AM Roberts, DJ Goldstein, AM AF Doyle, AM Roberts, DJ Goldstein, AM TI Enteric nervous system patterning in the avian hindgut SO DEVELOPMENTAL DYNAMICS LA English DT Article DE enteric nervous system; Hirschsprung's disease; chick; gut development ID SACRAL NEURAL CREST; CELL-MIGRATION; NEURONS; COLONIZATION; BOWEL; CHICK; GUT AB The enteric nervous system (ENS) is principally derived from vagal and sacral neural crest cells that migrate throughout the gastrointestinal tract before differentiating into neurons and glia. These cells form two concentric rings of ganglia and regulate intestinal motility, absorption, and secretion. Abnormalities of ENS development can lead to disorders of intestinal function, including Hirschsprung's disease. These disorders are generally limited to the distal hindgut, suggesting unique features to development of this region. This study characterized the normal spatiotemporal development of the ENS within the avian hindgut. Neural crest cells begin to populate the hindgut at E8, with patterning of both plexuses complete by embryonic day 9. Crest-derived cells arrive in the submucosal layer before the myenteric layer, as well as differentiate to a neuronal phenotype first. The cloaca demonstrates a unique pattern, characterized by a disorganized myenteric plexus and a flattened nerve of Remak. Detailed understanding of normal avian hindgut ENS development will allow better utilization of this model system to study abnormalities of the intestinal nervous system. Developmental Dynamics 229.-708-71Z 2004. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. EM agoldstein@partners.org FU NICHD NIH HHS [HD39942, HD34448] NR 18 TC 13 Z9 13 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2004 VL 229 IS 3 BP 708 EP 712 DI 10.1002/dvdy.20011 PG 5 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 780EP UT WOS:000189359600033 PM 14991727 ER PT J AU Lechner, A Yang, YG Blacken, RA Wang, L Nolan, AL Habener, JF AF Lechner, A Yang, YG Blacken, RA Wang, L Nolan, AL Habener, JF TI No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo SO DIABETES LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PRECURSOR CELLS; ISLETS; MICE; DIFFERENTIATION; REGENERATION; ENDOCRINE; FUSION; NEOVASCULARIZATION; TRANSPLANTATION AB Several recent studies have suggested that the adult bone marrow harbors cells that can differentiate into tissues from all three germ layers. Other reports have contradicted these findings or attributed them to cell fusion. In this study, we investigated whether bone marrow-derived cells contribute to the renewal of adult pancreatic endocrine cells, in particular insulin-producing beta-cells, in vivo. To address this issue, we studied mice transplanted with green fluorescent protein (GFP)-positive, sex-mismatched bone marrow. We also extended our studies to pancreatic injury models (partial pancreatectomy and streptozotocin administration). All animals showed stable full donor chimerism in the peripheral blood and microscopic analysis at 4-6 weeks and 3 months after transplantation, indicating that the GFP(+) and Y chromosome -positive donor bone marrow contributed substantially to blood, lymphatic, and interstitial cells in the pancreas. However, after examining > 100,000 beta-cells, we found only 2 beta-cells positive for GFP, both of which were in control animals without pancreatic injury. Thus our study results did not support the concept that bone marrow contributes significantly to adult pancreatic beta-cell renewal. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, 55 Fruit St,WEL 320, Boston, MA 02114 USA. EM jhabener@partners.org FU NIDDK NIH HHS [DK-60125] NR 36 TC 163 Z9 173 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 616 EP 623 DI 10.2337/diabetes.53.3.616 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500014 PM 14988245 ER PT J AU Hu, FB Meigs, JB Li, TY Rifai, N Manson, JE AF Hu, FB Meigs, JB Li, TY Rifai, N Manson, JE TI Inflammatory markers and risk of developing type 2 diabetes in women SO DIABETES LA English DT Article ID C-REACTIVE PROTEIN; NECROSIS-FACTOR-ALPHA; INSULIN-RESISTANCE ATHEROSCLEROSIS; SCOTLAND CORONARY PREVENTION; INNATE IMMUNE-SYSTEM; ACUTE-PHASE PROTEINS; LIFE-STYLE; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; METABOLIC SYNDROME AB We conducted a prospective, nested, case-control study of inflammatory markers as predictors of type 2 diabetes among 32,826 women who provided blood samples in 1989 through 1990 in the Nurses' Health Study. Among women free of diabetes, cardiovascular disease, or cancer at baseline, 737 had developed diabetes by 2000. Control women (n = 785) were selected matched on age, fasting status, race, and BMI for cases in the top BMI decile. Baseline levels of tumor necrosis factor (TNF)-alpha receptor 2, interleukin (IL)-6, and C-reactive protein (CRP) were significantly higher among case than control subjects (all P less than or equal to 0.001). After adjusting for BMI and other lifestyle factors, all three biomarkers significantly predicted diabetes risk; the odds ratios (ORs) comparing extreme quintiles were 1.64 (95% Cl 1.10-2.45) for TNF-alphaR2, 1.91 (1.27-2.86) for IL-6, and 4.36 (2.80-6.80) for CRP (P for trend <0.001 for all biomarkers). In a multivariate model simultaneously including the three biomarkers, only CRP levels were significantly associated with risk of diabetes (OR comparing extreme quintiles of CRP = 3.99, P for trend <0.001). These data support the role of inflammation in the pathogenesis of type 2 diabetes. Elevated CRP levels are a strong independent predictor of type 2 diabetes and may mediate associations of TNF-alphaR2 and IL-6 with type 2 diabetes. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Childrens Hosp, Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM frank.hu@channing.harvard.edu FU NCI NIH HHS [CA87969]; NIDDK NIH HHS [DK58845] NR 52 TC 395 Z9 417 U1 2 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 693 EP 700 DI 10.2337/diabetes.53.3.693 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500023 PM 14988254 ER PT J AU DeRubertis, FR Craven, PA Melhem, MF Salah, E AF DeRubertis, FR Craven, PA Melhem, MF Salah, E TI Attenuation of renal injury in db/db mice overexpressing superoxide dismutase - Evidence for reduced superoxide-nitric oxide interaction SO DIABETES LA English DT Article ID AORTIC ENDOTHELIAL-CELLS; GROWTH-FACTOR-BETA; ALPHA-LIPOIC ACID; PROTEIN-KINASE-C; OXIDATIVE STRESS; DIABETIC-RATS; GLOMERULAR INJURY; MESANGIAL CELLS; VITAMIN-C; NEPHROPATHY AB The effects of overexpression of Cu2+/Zn2+ superoxide dismutase-1 (SOD-1) on indexes of renal injury were compared in 5-month-old nontransgenic (NTg) db/db mice and db/db mice hemizygous for the human SOD-1 transgene (SOD-Tg). Both diabetic groups exhibited similar hyperglycemia and weight gain. However, in NTg-db/db mice, albaminuria, glomerular accumulation of immunoreactive transforming growth factor-beta, collagen alpha1(IV), nitrotyrosine, and mesangial matrix were all significantly increased compared with either nondiabetic mice or SOD-Tg-db/db. SOD-1 activity and reduced glutathione levels were higher, whereas malondialdehyde content was lower, in the renal cortex of SOD-Tg-db/db compared with NTg-db/db mice, consistent with a renal antioxidant effect in the transgenic mice. Inulin clearance (C-IN) and urinary excretion of guanosine 3',5'-cyclic monophosphate (U-cGMP) were increased in SOD-Tg-db/db mice compared with corresponding values in nondiabetic mice or NTg-db/db mice. C-IN and U-cGMP were suppressed by Nomega-nitro-L-arginine methyl ester in SOD-Tg-db/db but not in NTg-db/db mice, implying nitric oxide (NO) dependence of these increases and enhanced renal NO bioactivity in SOD-Tg-db/db. Studies of NO-responsive cGMP in isolated glomeruli supported greater quenching of NO in glomeruli from NTg-db/db compared with SOD-Tg-db/db mice. Evidence of increased NO responsiveness and the suppression of glomerular nitrotyrosine may both reflect reduced NO-superoxide interaction in SOD-Tg-db/db mice. The results implicate superoxide in the pathogenesis of diabetic nephropathy. C1 VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Dept Pathol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP DeRubertis, FR (reprint author), VA Pittsburgh Healthcare Syst, Dept Med, Univ Dr C, Pittsburgh, PA 15240 USA. EM frederick.derubertis@med.va.gov NR 49 TC 86 Z9 90 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 762 EP 768 DI 10.2337/diabetes.53.3.762 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500031 PM 14988262 ER PT J AU Ng, DPK Walker, WH Chia, KS Choo, S Warram, JH Krolewski, AS AF Ng, DPK Walker, WH Chia, KS Choo, S Warram, JH Krolewski, AS TI Scrutiny of the glutamine-fructose-6-phosphate transaminase 1 (GFPT1) locus reveals conserved haplotype block structure not associated with diabetic nephropathy SO DIABETES LA English DT Article ID HEXOSAMINE PATHWAY; MESANGIAL CELLS; OVEREXPRESSION; IDENTIFICATION; GLUTAMINE; PROMOTER; VARIANT; GFAT1 AB Glutamine-fructose-6-phosphate transaminase 1 (GFAT) is the rate-limiting enzyme of the hexosamine pathway that has been implicated in the pathogenesis of diabetic nephropathy. As such, we hypothesized that GFPT1, which encodes for GFAT, may confer genetic susceptibility to this complication among Caucasians. Screening of all known functional regions of GFPT1 revealed six single nucleotide polymorphisms (SNPs) that were located in the promoter, introns, and 3' untranslated region. The similar to60 kb GFPT1 locus was encompassed in a single conserved haplotype block, and two tagging SNPs were sufficient to capture >90% of the haplotype diversity. Analysis of these SNPs in a case-control study made up of type I diabetic subjects (324 case subjects with diabetic nephropathy and 289 control subjects with normoalbuminuria despite >15 years of diabetes) revealed no significant association even after stratification by sex, diabetes duration, glucose control, and blood pressure. Similar results were obtained among type 2 diabetic subjects (202 case and 114 control subjects). Genetic variation in GFPT1 is thus unlikely to have a major impact on susceptibility to diabetic nephropathy. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Natl Univ Singapore, Singapore 117548, Singapore. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu RI CHIA, Kee Seng/C-5790-2011 FU NIDDK NIH HHS [DK041526, DK053534, DK058549] NR 15 TC 6 Z9 7 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 865 EP 869 DI 10.2337/diabetes.53.3.865 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500046 PM 14988277 ER PT J AU Cohen, SE Tseng, YH Michael, MD Kahn, CR AF Cohen, SE Tseng, YH Michael, MD Kahn, CR TI Effects of insulin-sensitising agents in mice with hepatic insulin resistance SO DIABETOLOGIA LA English DT Article DE thiazolidinedione; rosiglitazone; metformin; diabetes mellitus ID DIABETES-MELLITUS; THIAZOLIDINEDIONES; MECHANISM; METFORMIN; GLUCOSE AB Aims/hypothesis. The metabolic abnormalities of insulin resistance are ameliorated by insulin sensitisers via different mechanisms. Metformin decreases hepatic glucose output, whereas rosiglitazone (RSG) is an agonist for peroxisome proliferator activated receptor (PPAR)gamma, highly expressed in fat. To gain insight into the mechanisms of action of these drugs, we compared their actions in two models of insulin resistance: the obese, hyperglycaemic ob/ob mouse and the liver specific insulin receptor knockout (LIRKO) mouse. Methods. Control, ob/ob, and LIRKO mice were divided into three groups that received metformin (300 mg/kg body weight/day), RSG (3 mg/kg body weight/day), or placebo for 3 weeks. Results. In the presence of the severe hepatic insulin resistance of the LIRKO mouse, neither metformin nor RSG had any significant effect on glucose or insulin tolerance tests. On the other hand, RSG decreased serum concentrations of total cholesterol, LDL, and HDL in LIRKO mice. Adipocyte PPARgamma gene and protein expression, and adipocyte size were all increased in LIRKO mice treated with RSG, whereas fat-cell size in control animals was decreased by RSG. Conclusion/interpretation. TZDs probably improve some lipid parameters of the dysmetabolic syndrome associated with diabetes mellitus even in the presence of absolute hepatic insulin resistance, but both metformin and TZDs require an operating insulin signalling system in the liver for their effects in glucose homeostasis. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu NR 11 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 2004 VL 47 IS 3 BP 407 EP 411 DI 10.1007/s00125-003-1320-4 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 808IP UT WOS:000220563100007 PM 14730378 ER PT J AU Johnson, BE AF Johnson, BE TI New targets and new treatments in non-small cell lung cancer SO EJC SUPPLEMENTS LA English DT Article; Proceedings Paper CT Symposium on Thoracic Malignancies CY MAR 08, 2003 CL Barcelona, SPAIN DE lung neoplasm; carcinoma; non-small cell; receptor; genes; erbB-1; genes; erbB-2; angiogenesis inhibitors; matrix metalloproteinase ID RECEPTOR TYROSINE KINASE; QUALITY-OF-LIFE; PHASE-II TRIAL; INHIBITORS; CISPLATIN; CHEMOTHERAPY; VINORELBINE; GEFITINIB; SURVIVAL AB New agents directed against molecular targets have now been tested in large prospectively randomized clinical trials for patients with untreated advanced non-small cell lung cancer (NSCLC). The trials have included small molecule inhibitors of receptor tyrosine kinases (gefitinib and erlontinib), monoclonal antibodies directed against either the ligands (bevicizumab against vascular endothelial growth factor) or their receptors (trastuzumab against ErbB2) and antisense nucleotides directed against mRNA coding for molecular targets (ISIS 3521 against protein kinase C alpha). The largest mature trials have included agents directed against ErbB1 (epidermal growth factor receptor). Two different small molecule inhibitors of erbB1 (gefitinib and erlontinib) and have been tested in 4 large international randomized trials. Two trials treated patients with advanced NSCLC with either gemcitabine and cisplatin or the same chemotherapy drugs combined with two different doses of gefitinib or one dose of erlontinib (INTACT I and TALENT). The other two trials treated patients with advanced NSCLC with either paclitaxel and carboplatin or the same chemotherapy drugs combined with either one of two doses of gefitinib or a single dose of erlontinib (INTACT 2 or TRIBUTE respectively). The results of INTACT I and INTACT2 showed no significant difference in survival between those treated with conventional combination chemotherapy and those treated with the same chemotherapy plus gefitinib. The results of the TRIBUTE and TALENT studies showed their primary endpoints of improving overall survival were not met. The monoclonal antibody, bevacizumab, is being tested in an ongoing clinical trial. The trial will compare the outcome of patients with untreated advanced adenocarcinoma of the lung treated with paclitaxel plus carboplatin to those treated with the same chemotherapy drugs plus bevacizumab. The results are scheduled to be available in 2005-2006. Although the initial trials adding newly developed molecular targeted agents have not shown initial success when added to conventional combination chemotherapy, further clinical trials are needed to ultimately define their role in the treatment of non-small cell lung cancer. (C) 2004 Elsevier Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Dept Med, Boston, MA 02445 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02445 USA. RP Johnson, BE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Dept Med, 44 Binney St, Boston, MA 02445 USA. EM bejohnson@partners.org NR 27 TC 39 Z9 40 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 MAR PY 2004 VL 2 IS 4 BP 1 EP 6 DI 10.1016/j.ejcsup.2003.11.001 PG 6 WC Oncology SC Oncology GA 837LM UT WOS:000222631900001 ER PT J AU Winer, E AF Winer, E. TI The validity of research/clinical trials of CAM SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 [Winer, E.] Dana Farber Canc Inst, Boston, MA 02115 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 MAR PY 2004 VL 2 IS 3 MA 357 BP 161 EP 161 DI 10.1016/S1359-6349(04)90960-3 PG 1 WC Oncology SC Oncology GA V44GB UT WOS:000202990100374 ER PT J AU Albrecht-Betancourt, M Hijazi, RA Cunningham, GR AF Albrecht-Betancourt, M Hijazi, RA Cunningham, GR TI Androgen replacement in men with hypogonadism and erectile dysfunction SO ENDOCRINE LA English DT Article DE testosterone; androgen; hypogonadism; libido; erectile dysfunction ID TRANSDERMAL TESTOSTERONE GEL; SLEEP-RELATED ERECTIONS; SEXUAL-BEHAVIOR; SERUM TESTOSTERONE; ELECTRICAL-STIMULATION; PENILE TUMESCENCE; LONG-TERM; THERAPY; HORMONES; BRAIN AB The prevalence of hypogonadism and erectile dysfunction (ED) increases with age. Hypogonadism also is frequently associated with decreased libido and ED. Testosterone replacement therapy for hypogonadal ED is effective in restoring sexual desire and erectile function, especially in younger and healthy men. It appears to be less effective in older men with comorbid diseases that may cause ED. Therapy should be individualized, considered carefully, and closely monitored because of potential risks, especially in older men. The FDA has approved several testosterone delivery systems. These include a buccal testosterone tablet, intramuscular injections, transdermal and subcutaneous forms. There also are several promising experimental androgens under investigation including non-steroidal selective androgen receptor modulators (SARMs). C1 Baylor Coll Med, Dept Med, Houston, TX USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX USA. VA Med Ctr, Houston, TX USA. RP Cunningham, GR (reprint author), VA Med Ctr 151, 2002 Holcombe Blvd, Houston, TX USA. EM glennc@bcm.tmc.edu NR 50 TC 8 Z9 8 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD MAR-APR PY 2004 VL 23 IS 2-3 BP 143 EP 148 DI 10.1385/ENDO:23:2-3:143 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 827IO UT WOS:000221893100011 PM 15146093 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate and accelerates chondrocyte differentiation in vitro SO ENDOCRINOLOGY LA English DT Article ID CHONDROGENIC DIFFERENTIATION; ATDC5 CELLS; BONE; CARTILAGE; RECEPTORS; LIMB; GENE AB Among the local signaling pathways that regulate the sequential steps of chondrocyte differentiation is the bone morphogenetic protein (BMP) signaling pathway. We have identified a novel gene, named BIG-3 (BMP-2-induced gene 3 kb) that is expressed in a BMP-regulated fashion in the prechondroblastic cell line MLB13MYC clone 17. BIG-3 is also expressed in proliferating and hypertrophic chondrocytes in the developing growth plate in vivo. We undertook studies to address whether BIG-3 played a functional role in chondrocyte differentiation, using mouse clonal chondrogenic ATDC5 cells. BIG-3 protein levels increased during ITS ( insulin, transferrin, sodium selenite)-induced ATDC5 differentiation and in response to BMP-2 treatment. To determine whether stable expression of BIG-3 could alter the program of chondrocytic differentiation, ATDC5 cells were stably transfected with the full-length coding region of BIG-3 (ATDC5-BIG-3) or with the empty vector (ATDC5-EV). Accelerated matrix proteoglycan synthesis was observed in the pooled ATDC5-BIG-3 clones. Alkaline phosphatase and osteopontin mRNA levels were also increased in ATDC5-BIG-3 clones compared with ATDC5-EV clones. Stable expression of BIG-3 also accelerated mineralized matrix formation in both the presence and absence of ITS. These findings, which demonstrate that BIG-3 accelerates chondrocyte differentiation in vitro, combined with the observation that BIG-3 is expressed in the growth plate during embryonic development, suggest that this novel protein is likely to play an in vivo regulatory role in the developing growth plate. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Gori, F (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. EM gori@helix.mgh.harvard.edu FU NIDCR NIH HHS [1 F32 DE-05754]; NIDDK NIH HHS [DK36597] NR 21 TC 15 Z9 16 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1050 EP 1054 DI 10.1210/en.2003-1314 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500006 PM 14657013 ER PT J AU Barbour, LA Shao, JH Qiao, LP Leitner, W Anderson, M Friedman, JE Draznin, B AF Barbour, LA Shao, JH Qiao, LP Leitner, W Anderson, M Friedman, JE Draznin, B TI Human placental growth hormone increases expression of the p85 regulatory unit of phosphatidylinositol 3-kinase and triggers severe insulin resistance in skeletal muscle SO ENDOCRINOLOGY LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; PHOSPHOINOSITIDE 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; 3T3-L1 ADIPOCYTES; P85-ALPHA SUBUNIT; TRANSGENIC MICE; GLUCOSE-UPTAKE; GH RECEPTOR; OBESE WOMEN AB The insulin resistance of normal pregnancy is necessary to divert fuels to the fetus to meet fetal growth demands and is mediated by placental hormones. We recently demonstrated that human placental GH (hPGH) can trigger severe insulin resistance in transgenic (TG) mice. In this study we sought to elucidate the cellular mechanisms by which hPGH interferes with insulin signaling in muscle in TG mice. Insulin-stimulated GLUT-4 translocation to the plasma membrane ( PM) was reduced in the TG compared with wild-type (WT) mice ( P = 0.05). Insulin receptor (IR) levels were modestly reduced by 19% ( P < 0.01) in TG mice, but there were no changes in phosphorylation of IR or IR substrate-1 (IRS-1) between WT and TG mice. A singular finding was a highly significant increase in the p85α regulatory subunit of phosphatidylinositol 3-kinase ( PI 3-kinase; P < 0.001), yet a reduced ability of insulin to stimulate IRS-1-associated PI 3-kinase activity ( P < 0.05). Although the levels of the p110 catalytic subunit protein of PI 3-kinase and IRS-1 were unchanged in the TG mice, insulin's ability to stimulate p110 association with IRS-1 was markedly reduced ( P < 0.0001). We demonstrate a unique mechanism of insulin resistance and suggest that hPGH may contribute to the insulin resistance of normal pregnancy by increasing the expression of the p85alpha monomer, which competes in a dominant negative fashion with the p85-p110 heterodimer for binding to IRS-1 protein. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80262 USA. RP Barbour, LA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, 4200 E 9th Ave,Box B-198, Denver, CO 80262 USA. EM lynn.barbour@uchsc.edu FU NCRR NIH HHS [1K23-RR-017496-01]; NIDDK NIH HHS [DK-62155] NR 25 TC 90 Z9 90 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1144 EP 1150 DI 10.1210/en.2003-1297 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500020 PM 14633976 ER PT J AU Houk, CP Pearson, EJ Martinelle, N Donahoe, PK Teixeira, J AF Houk, CP Pearson, EJ Martinelle, N Donahoe, PK Teixeira, J TI Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens SO ENDOCRINOLOGY LA English DT Article ID ANTI-MULLERIAN HORMONE; LEYDIG TUMOR-CELLS; STAR GENE; MOUSE OVARY; SUBSTANCE; RECEPTOR; GROWTH; PROGESTERONE; DIFFERENTIATION; PHOSPHORYLATION AB Mullerian-inhibiting substance (MIS) reduces testosterone synthesis in Leydig cells by inhibiting cytochrome P450C17 hydroxylase/C17-20 lyase expression. However, in mouse Leydig MA-10 cells, MIS also enhances the cAMP-induced expression of mRNA for steroidogenic acute regulatory protein (StAR), which transports cholesterol to the inner mitochondrial membrane for conversion to pregnenolone. We hypothesized that the MIS-induced StAR expression is the indirect result of reduced testosterone synthesis in Leydig cells caused by MIS. We show that, in addition to MIS, flutamide, an androgen receptor antagonist, enhanced StAR mRNA expression when added to cAMP-treated MA-10 cells, whereas dihydrotestosterone, a potent androgen receptor agonist, attenuated these responses. Progesterone, dexamethasone, and estradiol also inhibited StAR mRNA expression. Addition of MIS to cAMP-treated MA-10 cells transfected with a StAR-promoter luciferase reporter resulted in increased StAR promoter activity over cAMP alone; this effect was inhibited by dihydrotestosterone, suggesting that androgens inhibit StAR mRNA expression at the transcriptional level. Androgen-mediated inhibition of StAR expression was also observed in primary Leydig cell culture and in vivo using both hypophysectomized mice and mice treated with the GnRH antagonist, acyline. These results suggest that the induction of StAR expression by MIS occurs secondary to the MIS-mediated reduction in testosterone synthesis by relieving a hitherto uncharacterized androgen-dependent feedback inhibition on StAR expression. These findings may impact future treatment strategies aimed at reducing androgen; for example, in the treatment of prostatic cancer, antiandrogen treatment might benefit from adjuvant therapy to inhibit StAR expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs, 32 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NCI NIH HHS [R29-CA79459, R29 CA079459, R29 CA079459-05]; NICHD NIH HHS [F32-HD41835, R01-HD32112, U54 HD28138] NR 39 TC 40 Z9 40 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1269 EP 1275 DI 10.1210/en.2003-1046 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500034 PM 14630719 ER PT J AU Shin, HI Divieti, P Sims, NA Kobayashi, T Miao, DS Karaplis, AC Baron, R Bringhurst, R Kronenberg, HM AF Shin, HI Divieti, P Sims, NA Kobayashi, T Miao, DS Karaplis, AC Baron, R Bringhurst, R Kronenberg, HM TI gp130-mediated signaling is necessary for normal osteoblastic function in vivo and in vitro SO ENDOCRINOLOGY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; COLONY-STIMULATING FACTOR; NF-KAPPA-B; PARATHYROID-HORMONE; OSTEOCLAST DIFFERENTIATION; BONE-RESORPTION; TARGETED DISRUPTION; RECEPTOR ACTIVATOR; INTERLEUKIN-6; CYTOKINES AB Previous studies have shown that mice missing gp130, the common receptor subunit for many cytokines, die at or before birth with multiple skeletal abnormalities. Furthermore, interactions between PTH and gp130 signaling have suggested that gp130 signaling might influence calcium homeostasis. We, therefore, examined the function of osteoblasts, osteoclasts, and calcium homeostasis in gp130(-/-) mice, both in vivo and in vitro. Osteoblasts from these mice exhibit widespread abnormalities, including decreased alkaline phosphatase mRNA and protein, both in vivo and in osteoblast cultures. Although osteoclast number is increased in gp130(-/-) fetuses, these osteoclasts exhibit abnormalities in the resorptive organelle and the ruffled border, and the mice are mildly hypocalcemic. Although the hypocalcemia is associated with secondary hyperparathyroidism, the increase in PTH does not explain the increase in osteoclast number because removal of the PTH gene in gp130(-/-) fetuses does not importantly change osteoclast number. Calvarial bone resorption in response to PTH is defective, as is the ability of osteoblastic cells from gp130(-/-) mice to stimulate osteoclastogenesis from normal precursors in vitro or to increase receptor activator of nuclear factor-kappaB ligand mRNA levels after exposure to PTH. These studies demonstrate the importance of gp130 signaling for osteoblast function and calcium homeostasis. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Orthoped, New Haven, CT 06510 USA. McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Ctr Hlth, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1A1, Canada. Sir Mortimer B Davis Jewish Hosp, Lady Davis Res Inst, Montreal, PQ H3T 1A1, Canada. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu OI Sims, Natalie/0000-0003-1421-8468 NR 28 TC 32 Z9 32 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1376 EP 1385 DI 10.1210/en.2003-0839 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500048 PM 14617570 ER PT J AU He, ZH King, GL AF He, ZH King, GL TI Microvascular complications of diabetes SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID PROTEIN-KINASE-C; GLYCATION END-PRODUCTS; ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; ALDOSE REDUCTASE INHIBITION; GLOMERULAR MESANGIAL CELLS; NERVE-CONDUCTION-VELOCITY; PKC-BETA INHIBITOR; CONVERTING ENZYME-INHIBITION AB Several theories of the pathogenesis of microvascular complications of diabetes (diabetic retinopathy, nephropathy, and neuropathy) have been proposed: (1) generation of reactive oxygen species and oxidative stress, (2) activation of polyol pathway, (3) formation of advanced glycation end products, (4) induction of flux through the hexosamine pathway, (5) altered expression and action of growth factors, and (6) activation of protein kinase C. Based on these theories, specific interventions are feasible to prevent the development of diabetic complications even if satisfactory euglycemic control is not achieved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, 1 Joslin Pl, Boston, MA 02215 USA. EM George.King@joslin.harvard.edu NR 197 TC 70 Z9 80 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 EI 1558-4410 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 2004 VL 33 IS 1 BP 215 EP + DI 10.1016/j.ecl.2003.12.003 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 814GC UT WOS:000220962200015 PM 15053904 ER PT J AU Pulsifer, MB Brandt, J Salorio, CF Vining, EPG Carson, BS Freeman, JM AF Pulsifer, MB Brandt, J Salorio, CF Vining, EPG Carson, BS Freeman, JM TI The cognitive outcome of hemispherectomy in 71 children SO EPILEPSIA LA English DT Article DE hemispherectomy; neuropsychology ID CHILDHOOD EPILEPSY; SHORT FORM; HEMIPLEGIA; INTELLIGENCE; LANGUAGE; SPEECH; SCALE AB Purpose: Long-term neuropsychological outcome was studied in 71 Patients Who Underwent hemispherectomy for severe and intractable seizures Lit The Johns Hopkins Hospital between 1968 and 1997 and who agreed to participate. Seizures were due to cortical dysplasias (n = 27), Rasmussen syndrome (n = 37). or vascular malformations or strokes (n = 7). Both presurgical and follow-up results are available and reported for 53 patients. Methods: Patients and caretakers were interviewed, and patients were administered standard measures of intelligence, receptive and expressive language visual-motor skills, adaptive/developmental functioning, and behavior. Results: Mean age at surgery was 7.2 years. At follow-up, Oil average 5.4 years after surgery. 65%, are seizure free, 49% are medication free, and, of those responding. none rated quality of life as worse than before surgery. Mean IQ was in the 70s for Rasmussen and vascular patients and in the 30s for cortical dysplasia patients. Language and visual-motor skills were consistent with IQ. For Rasmussen patients only, language was significantly more impaired for left than for right hemispherectomy, both before surgery and at follow-up. Adaptive skills were mildly impaired, with greatest impairment in the physical domain. Cognitive measures typically changed little between surgery and follow-up, With IQ change < 15 points for 34 of 53 patients of the remainder, 11 declined and eight improved. Behavior was free of major problems, but social interactions and activities were limited. Conclusions: The most significant predictor of cognitive skills at follow-up was etiology, with dysplasia patients scoring lowest in intelligence and language but not in visual motor skills. Regardless of etiology, most patients showed only moderate change in cognitive performance at follow-up. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Pediat Epilepsy Ctr, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA. RP Pulsifer, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. EM mpulsifer@partners.org RI shengkun, yu/B-8440-2012; OI Brandt, Jason/0000-0001-7381-6244 NR 36 TC 98 Z9 101 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 2004 VL 45 IS 3 BP 243 EP 254 DI 10.1111/j.0013-9580.2004.15303.x PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 802WG UT WOS:000220193000008 PM 15009226 ER PT J AU Keane, D Mansour, M Singh, J AF Keane, D Mansour, M Singh, J TI Detection by intracardiac echocardiography of early formation of left atrial thrombus during pulmonary vein isolation SO EUROPACE LA English DT Article ID RADIOFREQUENCY CATHETER ABLATION C1 Massachusetts Gen Hosp, Intervent Cardiac Electrophysiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Keane, D (reprint author), Massachusetts Gen Hosp, Intervent Cardiac Electrophysiol, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. EM dkeane@stjames.ie NR 3 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1099-5129 J9 EUROPACE JI Europace PD MAR PY 2004 VL 6 IS 2 BP 109 EP 110 DI 10.1016/j.eupc.2003.11.001 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 801YO UT WOS:000220131400005 PM 15018867 ER PT J AU Bruder, D Probst-Kepper, M Westendorf, AM Geffers, R Beissert, S Loser, K von Boehmer, H Buer, J Hansen, W AF Bruder, D Probst-Kepper, M Westendorf, AM Geffers, R Beissert, S Loser, K von Boehmer, H Buer, J Hansen, W TI Neuropilin-1: a surface marker of regulatory T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE immune regulation; gene expression profiling; surface marker; neuropilin-1 ID IN-VIVO; RECEPTOR; EXPRESSION; INTERLEUKIN-10; SECRETION; TOLERANCE; ANTIGEN; FOXP3 AB CD4(+)CD25(+) regulatory T cells (T-reg cells) control immune responsiveness to a large variety of antigens. The isolation and therapeutic manipulation of T-reg cells requires the use of reliable surface receptors that are selectively up-regulated in T-reg cells. On the basis of global gene expression studies, we identified neuropilin-1 (Nrp1) as a specific surface marker for CD4(+)CD25(+) T-reg cells. Nrp1, a receptor involved in axon guidance, angiogenesis, and the activation of T cells, is constitutively expressed on the surface of CD4(+)CD25(+) T-reg cells independently of their activation status. In contrast, Nrp1 expression is down-regulated in naive CD4(+)CD25(-) T cells after TCR stimulation. Furthermore, CD4(+)Nrp1(high) T cells express high levels of Foxp3 and suppress CD4(+)CD25(-) T cells. Thus, Nrp1 constitutes a useful surface marker to distinguish T-reg cells from both naive and recently activated CD4(+)CD25(+) nonregulatory T cells. C1 German Res Ctr Biotechnol, Dept Cell Bio & Immunol, D-38124 Braunschweig, Germany. Hannover Med Sch, Dept Visceral & Transplant Surg, D-3000 Hannover, Germany. Univ Munster, Dept Dermatol, D-4400 Munster, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hannover Med Sch, Inst Med Microbiol, D-3000 Hannover, Germany. RP Buer, J (reprint author), German Res Ctr Biotechnol, Dept Cell Bio & Immunol, Mascheroder Weg 1, D-38124 Braunschweig, Germany. EM jab@gbf.de NR 21 TC 261 Z9 298 U1 1 U2 5 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2004 VL 34 IS 3 BP 623 EP 630 DI 10.1002/eji.200324799 PG 8 WC Immunology SC Immunology GA 802WH UT WOS:000220193100002 PM 14991591 ER PT J AU Bloechlinger, S Karchewski, LA Woolf, CJ AF Bloechlinger, S Karchewski, LA Woolf, CJ TI Dynamic changes in glypican-1 expression in dorsal root ganglion neurons after peripheral and central axonal injury SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE adult; dorsal column; DRG; growth; heparan sulphate proteoglycan; nerve injury; rat; regeneration; robo; sensory neuron; slit; spinal cord ID HEPARAN-SULFATE PROTEOGLYCAN; PRIMARY SENSORY NEURONS; RAT SPINAL-CORD; MYELIN-ASSOCIATED GLYCOPROTEIN; NERVE INJURY; ADULT-RAT; SLIT PROTEIN; C-JUN; NEUROPATHIC PAIN; GENE-EXPRESSION AB Glypican-1, a glycosyl phosphatidyl inositol (GPI)-anchored heparan sulphate proteoglycan expressed in the developing and mature cells of the central nervous system, acts as a coreceptor for diverse ligands, including slit axonal guidance proteins, fibroblast growth factors and laminin. We have examined its expression in primary sensory dorsal root ganglion (DRG) neurons and spinal cord after axonal injury. In noninjured rats, glypican-1 mRNA and protein are constitutively expressed at low levels in lumbar DRGs. Sciatic nerve transection results in a two-fold increase in mRNA and protein expression. High glypican-1 expression persists until the injured axons reinnervate their peripheral targets, as in the case of a crushed nerve. Injury to the central axons of DRG neurons by either a dorsal column injury or a dorsal root transection also up-regulates glypican-1, a feature that differs from most DRG axonal injury-induced genes, whose regulation changes only after peripheral and not central axonal injury. After axonal injury, the cellular localization of glypican-1 changes from a nuclear pattern restricted to neurons in noninjured DRGs, to the cytoplasm and membrane of injured neurons, as well as neighbouring non-neuronal cells. Sciatic nerve transection also leads to an accumulation of glypican-1 in the proximal nerve segment of injured axons. Glypican-1 is coexpressed with robo 2 and its up-regulation after axonal injury may contribute to an altered sensitivity to axonal growth or guidance cues. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, MGH E, Charlestown, MA 02129 USA. RP Karchewski, LA (reprint author), ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire,UMR7104, Parc Innovat,1 Rue Laurent Fries BP 10142, F-67404 Illkirch Graffenstaden, CU Strasbourg, France. EM lkarch@igbmc.u-strasbg.fr FU NICHD NIH HHS [HD38533]; NINDS NIH HHS [NS38253] NR 62 TC 32 Z9 35 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2004 VL 19 IS 5 BP 1119 EP 1132 DI 10.1111/j.1460-9568.2004.03262.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 802QA UT WOS:000220176800001 PM 15016071 ER PT J AU Zhu, ZT Munhall, A Shen, KZ Johnson, SW AF Zhu, ZT Munhall, A Shen, KZ Johnson, SW TI Calcium-dependent subthreshold oscillations determine bursting activity induced by N-methyl-D-aspartate in rat subthalamic neurons in vitro SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE brain slice; burst firing; firing pattern; subthalamic nucleus; whole-cell recording ID METABOTROPIC GLUTAMATE RECEPTORS; ACTIVATED POTASSIUM CHANNELS; ACTION-POTENTIAL GENERATION; SINGLE-SPIKE ACTIVITY; MOUSE CENTRAL NEURONS; NUCLEUS NEURONS; NEUROTRANSMITTER RELEASE; PLATEAU POTENTIALS; PARKINSONS-DISEASE; PYRAMIDAL NEURONS AB We used whole-cell patch recordings in current clamp to investigate the ionic dependence of burst firing induced by N-methyl-d-aspartate (NMDA) in neurons of the subthalamic nucleus (STN) in slices of rat brain. NMDA (20 mum) converted single-spike firing to burst firing in 87% of STN neurons tested. NMDA-induced bursting was blocked by AP5 (50 mum), and was not mimicked by the non-NMDA receptor agonist AMPA (0.6 mum). Tetrodotoxin (1 mum) converted bursts to oscillations of membrane potential, which were most robust when oscillations ranged between -50 and -70 mV. The NMDA bursts were blocked by an elevated extracellular concentration of Mg2+, but superfusate containing no added Mg2+ either reduced or increased burst firing, depending upon the amount of intracellular current injection. Block of K+ conductances by apamin and tetraethylammonium prolonged burst duration, but iberiotoxin had no effect. NMDA-induced burst firing and membrane oscillations were completely blocked by superfusate containing no added Ca2+, and they were significantly reduced when patch pipettes contained BAPTA. Selective antagonists for T-type (mibefradil, 10 mum), L-type (nifedipine, 3 mum), and N-type (omega-conotoxin GVIA, 1 mum) Ca2+ channels had no effect on NMDA burst firing. Superfusate containing a low concentration of Na+ (20 mm) completely abolished NMDA-induced burst firing. Flufenamic acid (10 mum), which blocks current mediated by Ca2+-activated nonselective cation channels (I-CAN), reversibly abolished NMDA-depended bursting. These results are consistent with the hypothesis that NMDA-induced burst firing in STN neurons requires activation of either an I-CAN or a Na+-Ca2+ exchanger. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd,POB 1034, Portland, OR 97207 USA. EM johnsost@ohsu.edu FU NINDS NIH HHS [NS38715] NR 72 TC 42 Z9 42 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2004 VL 19 IS 5 BP 1296 EP 1304 DI 10.1111/j.1460-9568.2004.03240.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 802QA UT WOS:000220176800017 PM 15016087 ER PT J AU Papakostas, GI Ongur, D Iosifescu, DV Mischoulon, D Fava, M AF Papakostas, GI Ongur, D Iosifescu, DV Mischoulon, D Fava, M TI Cholesterol in mood and anxiety disorders: review of the literature and new hypotheses SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE cholesterol; depression; anxiety; suicide; membrane; fluidity ID LOW SERUM-CHOLESTEROL; MAJOR DEPRESSIVE DISORDER; VIOLENT SUICIDE ATTEMPTERS; PLASMA-MEMBRANE FLUIDITY; GAMMA-SECRETASE ACTIVITY; META-CHLOROPHENYLPIPERAZINE; ANGER ATTACKS; FENFLURAMINE CHALLENGE; PANIC DISORDER; HYPERCHOLESTEROLEMIC PATIENTS AB Cholesterol plays an integral role in the structure and function of the cell membrane and may also affect neurotransmission in the central nervous system. Previous work has identified abnormalities in serum cholesterol levels in patients with mood and anxiety disorders as well as in suicidal patients. However, the biological significance of these abnormalities remains to be clarified. An understanding of how serum cholesterol relates to the pathophysiology of mood disorders may generate biological markers that predict treatment response as well as targets for novel therapeutic strategies. In this article, we review the literature studying the significance of cholesterol in mood and anxiety disorders, with an emphasis on new studies focusing on the adverse impact of hypercholesterolemia on the treatment of major depressive disorder (MDD). We then propose possible mechanisms that would account for the relationship between elevated cholesterol and treatment non-response in MDD. (C) 2003 Elsevier B.V./ECNP. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 NR 109 TC 72 Z9 79 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2004 VL 14 IS 2 BP 135 EP 142 DI 10.1016/S0924-977X(03)00099-3 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 778EQ UT WOS:000189226800007 PM 15013029 ER PT J AU Dohlman, C AF Dohlman, C TI David Maurice - April 3rd 1922-July 20th 2002 - A recollection from Boston SO EXPERIMENTAL EYE RESEARCH LA English DT Biographical-Item C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & External Dis Serv, Boston, MA 02114 USA. RP Dohlman, C (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & External Dis Serv, Boston, MA 02114 USA. EM marylou_moar@meei.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2004 VL 78 IS 3 BP XXI EP XXII DI 10.1016/j.exer.2003.09.026 PG 2 WC Ophthalmology SC Ophthalmology GA 801EY UT WOS:000220080400004 PM 15106903 ER PT J AU Hatton, MP Perez, VL Dohlman, CH AF Hatton, MP Perez, VL Dohlman, CH TI Corneal oedema in ocular hypotony SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE corneal oedema; hypotony; intraocular pressure ID SWELLING PRESSURE; STROMA AB We describe the pattern of corneal oedema observed in five patients with chronic hypotony. The patients had marked stromal oedema from presumed endothelial dysfunction, but no epithelial oedema. These observations corroborate the concept that the intraocular pressure is the driving force in the generation of epithelial oedema. (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM marylou_moar@meei.harvard.edu NR 7 TC 3 Z9 3 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2004 VL 78 IS 3 BP 549 EP 552 DI 10.1016/j.exer.2003.06.003 PG 4 WC Ophthalmology SC Ophthalmology GA 801EY UT WOS:000220080400034 PM 15106934 ER PT J AU Gabison, E Chang, JH Hernandez-Quintela, E Javier, J Lu, PCS Ye, HQ Kure, T Kato, T Azar, DT AF Gabison, E Chang, JH Hernandez-Quintela, E Javier, J Lu, PCS Ye, HQ Kure, T Kato, T Azar, DT TI Anti-angiogenic role of angiostatin during corneal wound healing SO EXPERIMENTAL EYE RESEARCH LA English DT Review DE plasminogen; metalloproteinases; angiogenesis; endothelial cell proliferation; wound healing ID ENDOTHELIAL GROWTH-FACTOR; DEFICIENT MICE; GELATINASE-B; EXCIMER KERATECTOMY; ALLOGRAFT-REJECTION; ATP SYNTHASE; TUMOR-GROWTH; PLASMINOGEN; EXPRESSION; CELLS AB The purpose of this study is to determine whether angiostatin is involved in maintaining corneal avascularity after wounding. We generated polyclonal rabbit anti-mouse angiostatin antibodies directed against each of the five kringle domains, (KI-5) and anti-mouse plasmin B chain antibodies. Mouse corneas were immunostained with anti-K1 angiostatin antibody after excimer laser keratectomy. Corneal epithelial cell lysate was harvested and angiostatin was isolated using lysine Sepharose. Purified plasminogen was incubated with lysate of mouse corneal epithelial cells from wild type mice in the presence or absence of MMP inhibitors. Angiostatin activity was determined using calf pulmonary artery endothelial (CPAE) cell proliferation assay with and without angiostatin immunoprecipitation; and corneal neovascularization was assayed by intrastromal injection of anti-plasminogen, anti-K1-3 or anti-B chain antibodies after corneal wounding. Using the anti-mouse angiostatin antibodies that we generated, we confirmed that angiostatin-like molecules were expressed in the corneal epithelium and in cultured corneal epithelial cells. Western blotting after incubation of scraped corneal epithelial cell lysate with purified plasminogen showed reduction of the plasminogen bands at 6, 12, and 24 hr, respectively. Complete cleavage of plasminogen occurred by 48 hr. Functional assays in which corneal epithelial cell extracts were incubated with CPAE cells resulted in inhibition of vascular endothelial cell proliferation. Depletion experiments using anti-angiostatin (K I) antibodies resulted in a 25 +/- 1.2% increase in vascular endothelial cell proliferation as compared to 12 +/- 1.8% using the protein A control (p < 0.05). Corneal neovascularization was observed after excimer laser keratectomy when anti-angiostatin antibodies were injected into the cornea (65 +/- 13%) which was significantly higher than when plasmin B chain antibodies were injected (10 +/- 2.6%; p < 0.05). Plasminogen and angiostatin tire produced in the cornea. They may play a role in preventing vascularization and may contribute to the maintenance of corneal avascularity after excimer laser keratectomy. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Corneal & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY10101] NR 46 TC 36 Z9 41 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2004 VL 78 IS 3 BP 579 EP 589 DI 10.1016/j.exer.2003.09.005 PG 11 WC Ophthalmology SC Ophthalmology GA 801EY UT WOS:000220080400038 PM 15106938 ER PT J AU Mellough, CB Cui, Q Spalding, KL Symons, NA Pollett, MA Snyder, EY Macklis, JD Harvey, AR AF Mellough, CB Cui, Q Spalding, KL Symons, NA Pollett, MA Snyder, EY Macklis, JD Harvey, AR TI Fate of multipotent neural precursor cells transplanted into mouse retina selectively depleted of retinal ganglion cells SO EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; stem cells; differentiation; degeneration; Y-chromosome ID TARGETED APOPTOTIC DEGENERATION; ADULT MAMMALIAN EYE; OPTIC-NERVE LESION; STEM-LIKE CELLS; RAT RETINA; SUPERIOR COLLICULUS; NEONATAL-RATS; RD MICE; NEUROTROPHIC FACTOR; PIGMENT-EPITHELIUM AB In some parts of the CNS, depletion of a particular class of neuron might induce changes in the microenvironment that influence the differentiation of newly grafted neural precursor cells. This hypothesis was tested in the retina by inducing apoptotic retinal ganglion cell (RGC) death in neonatal and adult female mice and examining whether intravitreally grafted mate neural precursor cells (C17.2), a neural stem cell (NSC)-like clonal line, become incorporated into these selectively depleted retinae. In neonates, rapid RGC death was induced by removal of the contralateral superior colliculus (SC), in adults, delayed RGC death was induced by unilateral optic nerve (ON) transection. Cells were injected intravitreally 6-48 h after SC ablation (neonates) or 0-7 days after ON injury (adults). Cells were also injected into non-RGC depleted neonatal and adult retinae. At 4 or 8 weeks, transplanted cells were identified using a Y-chromosome marker and in situ hybridisation or by their expression of the lacZ reporter gene product Escherichia coli beta-galactosidase (beta-gal). No C17.2 cells were identified in axotomised adult-injected eyes undergoing delayed RGC apoptosis (n = 16). Donor cells were however stably integrated within the retina in 29% (15/55) of mice that received C17.2 cell injections 24 h after neonatal SC ablation; 6-31% of surviving cells were found in the RGC layer (GCL). These NSC-like cells were also present in intact retinae, but on average, there were fewer cells in GCL. In SC-ablated mice, most grafted cells did not express retinal-specific markers, although occasional donor cells in the GCL were immunopositive for beta-III tubulin, a protein highly expressed by, but not specific to, developing RGCs. Targeted rapid RGC depletion thus increased cell incorporation into the GCL, but grafted C17.2 cells did not appear to differentiate into an RGC phenotype. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Western Australia, Western Australian Inst Med Res, Sch Anat & Human Biol, Nedlands, WA 6009, Australia. Karolinska Inst, CMB, Med Noble Inst, S-17177 Stockholm, Sweden. Burnham Inst, Program Dev & Regenerat Cell Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGHHMS Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGHHMS Ctr Nervous Syst Repair,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGHHMS Ctr Nervous Syst Repair,Program Neurosci, Boston, MA 02114 USA. RP Harvey, AR (reprint author), Univ Western Australia, Western Australian Inst Med Res, Sch Anat & Human Biol, 35 Stirling Highway, Nedlands, WA 6009, Australia. EM arharvey@anhb.uwa.edu.au RI Harvey, Alan/A-4911-2008; OI Mellough, Carla/0000-0003-3685-6516 FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41290, NS45523] NR 84 TC 32 Z9 34 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 2004 VL 186 IS 1 BP 6 EP 19 DI 10.1016/j.expneurol.2003.10.021 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 779GR UT WOS:000189287400002 PM 14980806 ER PT J AU Devroe, E Silver, PA AF Devroe, E Silver, PA TI Therapeutic potential of retroviral RNAi vectors SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE cancer; gene therapy; HBV; HCV; HIV; lentivirus; retrovirus; RNAi; siRNA ID SMALL INTERFERING RNA; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B-VIRUS; HEMATOPOIETIC STEM-CELLS; LONG-TERM ENGRAFTMENT; ABL GENE-EXPRESSION; VIRAL MESSENGER-RNA; HUMAN CD34(+) CELLS; MAMMALIAN-CELLS; LENTIVIRAL VECTORS AB The ability of small interfering RNA (siRNA) to mediate gene-specific post-transcriptional silencing in mammalian cells will undoubtedly revolutionise functional genomics, as well as drug target identification and validation. Furthermore, there is widespread excitement that siRNA itself might prove useful in the clinical setting. For those wishing to develop siRNA as a therapeutic agent, the most difficult obstacle to overcome will be delivery. Recently, several breakthroughs have highlighted viruses as excellent vehicles for siRNA delivery. Retroviruses, the transgene-delivery vector of choice for many experimental gene therapy studies, have been engineered to deliver and stably express therapeutic siRNA within cells, both in vitro and in vivo. These findings are important milestones for the development of siRNA as a gene therapy for treatment of viral infections, cancer, autoimmune syndromes and numerous genetic disorders. This review describes the development of retroviral siRNA vectors, highlights proof-of-concept experiments demonstrating their therapeutic efficacy and explores therapeutic targets particularly suitable for retroviral-mediated gene silencing, C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM devroe@fas.harvard.edu; pamela_silver@dfci.harvard.edu NR 100 TC 49 Z9 51 U1 1 U2 4 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAR PY 2004 VL 4 IS 3 BP 319 EP 327 DI 10.1517/eobt.4.3.319.27320 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 802WK UT WOS:000220193400005 PM 15006726 ER PT J AU Willert, RP Woolf, CJ Hobson, AR Delaney, C Thompson, DG Aziz, Q AF Willert, RP Woolf, CJ Hobson, AR Delaney, C Thompson, DG Aziz, Q TI The development and maintenance of human visceral pain hypersensitivity is dependent on the N-methyl-D-aspartate receptor SO GASTROENTEROLOGY LA English DT Article ID NONNOXIOUS COLORECTAL DISTENSION; NMDA RECEPTOR; SPINAL-CORD; SECONDARY HYPERALGESIA; CENTRAL SENSITIZATION; NEURONAL PLASTICITY; HEALTHY-VOLUNTEERS; FOS EXPRESSION; GLYCINE SITE; KETAMINE AB Background&Aims: Visceral hypersensitivity is a common feature of functional gastrointestinal disorders. One speculated mechanism is an activity-dependent increase in spinal cord neuronal excitability (central sensitization), which is dependent on activation of the N-methyl-D-aspartate (NMDA) receptor. Our aims were to determine whether the development and maintenance of human visceral hypersensitivity is NMDA receptor mediated. Methods: Healthy subjects were studied using a randomized, double-blind, placebo-control led, crossover design. Pain thresholds to electrical stimulation were determined both in the proximal esophagus and in the foot (control) before and after a 30-minute distal esophageal infusion of 0.15 mol/L HCl acid. Ketamine (NMDA receptor antagonist) or saline (vehicle) was given intravenously either prior to or following acid infusion, and pain thresholds were measured for the following 120 minutes. Protocol 1: In 6 subjects, the effect of ketamine in the esophagus was assessed without acid infusion. Protocol 2: In :14 subjects, ketamine was given prior to esophageal acid. Protocol 3: In :12 subjects, ketamine was given after esophageal acid. Results: Protocol 1: In the absence of esophageal acid, ketamine had no effect on either esophageal or foot pain thresholds (area-under-the-curve, [AUC] P = 0.36 esophagus, P = 0.34 foot, ANOVA) within 30 minutes of cessation of the infusion. Protocol 2: Acid-induced esophageal hypersensitivity was prevented by ketamine (AUC, P < 0.0001, ANOVA) without affecting foot pain thresholds (AUC, P = 0.06, ANOVA). Protocol 3: Ketamine delivered after acid reversed the induction of esophageal hypersensitivity induced by acid (AUC, P < 0.0001, ANOVA). Conclusions: The induction and maintenance of acid-induced esophageal hypersensitivity is prevented and reversed by ketamine. This finding strongly indicates that central sensitization is a mechanism of visceral hypersensitivity. C1 Hope Hosp, GI Sci Grp, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02114 USA. RP Aziz, Q (reprint author), Hope Hosp, GI Sci Grp, Clin Sci Bldg, Salford M6 8HD, Lancs, England. EM qaziz@fs1.ho.man.ac.uk NR 72 TC 114 Z9 126 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2004 VL 126 IS 3 BP 683 EP 692 DI 10.1053/j.gastro.2003.11.047 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 802RC UT WOS:000220179600011 PM 14988822 ER PT J AU Beck, PL Wong, JF Li, Y Swaminathan, S Xavier, RJ Devaney, KL Podolsky, DK AF Beck, PL Wong, JF Li, Y Swaminathan, S Xavier, RJ Devaney, KL Podolsky, DK TI Chemotherapy- and radiotherapy-induced intestinal damage is regulated by intestinal trefoil factor SO GASTROENTEROLOGY LA English DT Article ID INDUCED GASTROINTESTINAL INJURY; INFLAMMATORY BOWEL-DISEASE; EPIDERMAL GROWTH-FACTOR; STEM-CELLS; ULCERATIVE MUCOSITIS; COLORIMETRIC ASSAY; EPITHELIAL-CELLS; FACTOR BETA-3; MICE LACKING; EXPRESSION AB Background&Aims: Injury to the intestinal mucosa is frequently a dose-limiting complication of radiotherapy and chemotherapy. Approaches to limit the damage to the intestine during radiation and chemotherapy have been largely ineffective. Trefoil factors are produced throughout the gastrointestinal tract and regulate cell migration, restitution, and repair. Studies were undertaken to define the role of intestinal trefoil factor in modulating the intestinal response to chemotherapy and radiation. Methods: The effect of intestinal trefoil factor on migration and cell survival in intestinal epithelial monolayer exposed to methotrexate was studied in vitro. Chemotherapy and radiation damage was assessed in wild-type and intestinal trefoil factor-null mice in the presence or absence of supplemental intestinal trefoil factor administered in drinking water. Results: Radiation and chemotherapy induced a marked reduction in goblet cell number and intestinal trefoil factor messenger RNA, as well as intestinal trefoil factor promoter activity. Intestinal trefoil factor improved intestinal epithelial cell viability and wound repair after chemotherapy exposure in vitro. Intestinal trefoil factor-deficient mice (intestinal trefoil factor(-/-)) were more susceptible to chemotherapy- and radiation-induced mucositis. Oral recombinant intestinal trefoil factor reduced the severity of both chemotherapy-induced and chemotherapy/radiotherapy-induced intestinal mucositis. Conclusions: These studies suggest that intestinal trefoil factor is involved in protection against and recovery from intestinal mucositis induced by radiation and chemotherapy. C1 Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Calgary, Gastrointestinal Res Grp, Calgary, AB, Canada. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. EM dpodolsky@partners.org FU NIDDK NIH HHS [DK07191, DK46906, DK43351] NR 43 TC 71 Z9 80 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2004 VL 126 IS 3 BP 796 EP 808 DI 10.1053/j.gastro.2003.12.004 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 802RC UT WOS:000220179600023 PM 14988834 ER PT J AU Liu, YY Liu, XS Wei, LP Altman, RB Batzoglou, S AF Liu, YY Liu, XS Wei, LP Altman, RB Batzoglou, S TI Eukaryotic regulatory element conservation analysis and identification using comparative genomics SO GENOME RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; NONCODING SEQUENCES; BINDING-SITES; MOUSE GENOME; DNA; ALIGNMENT; GENES; STRATEGIES; DISCOVERY; PROGRAMS AB Comparative genomics is a promising approach to the challenging problem of eukaryotic regulatory element identification, because functional noncoding sequences may be conserved across species from evolutionary constraints. We systematically analyzed known human and Saccharomyces cerevisiae regulatory elements and discovered that human regulatory elements are more conserved between human and mouse than are background sequences. Although S. cerevisiae regulatory elements do not appear to be more conserved by comparison of S. cerevisiae to Schizosaccharomyces pombe, they are more conserved when compared with multiple(? other yeast genomes (Saccharomyces paradoxus, Saccharomyces mikatae, and Saccharomyces bayanus). Based oil these analyses, we developed a sequence-motif-finding algorithm called CompareProspector, which extends Gibbs sampling by biasing the search ill regions conserved across species. Using human-mouse comparison, CompareProspector identified known motifs for transcription factors Mef2, Myf, Srf, and Spl from a set of human-muscle-specific genes. It also discovered the NFAT motif from genes up-regulated by CD28 stimulation ill T-cells, which implies the direct involvement of NFAT in mediating the CD28 stimulatory signal. Using Caenorhabditis elegans-Caenorhabditis briggsae comparison, CompareProspector found the PHA-4 motif and the UNC-86 motif. CompareProspector outperformed many other computational motif-finding programs, demonstrating the power of comparative genomics-based biased sampling in eukaryotic regulatory element identification. C1 Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. Stanford Univ, Stanford Med Informat, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Nexus Genom Inc, Mountain View, CA 94043 USA. RP Batzoglou, S (reprint author), Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. FU NHGRI NIH HHS [HG003162, U01 HG003162]; NIGMS NIH HHS [U01 GM061374, R24 GM061374] NR 32 TC 101 Z9 109 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2004 VL 14 IS 3 BP 451 EP 458 DI 10.1101/gr.1327604 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 780PB UT WOS:000189389100013 PM 14993210 ER PT J AU Wadler, S Levy, D Frederickson, HL Falkson, CI Wang, YX Weller, E Burk, R Ho, G Kadish, AS AF Wadler, S Levy, D Frederickson, HL Falkson, CI Wang, YX Weller, E Burk, R Ho, G Kadish, AS TI A phase II trial of interleukin-12 in patients with advanced cervical cancer: clinical and immunologic correlates Eastern Cooperative Oncology Group study E1E96 SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cell-mediated immunity; cytokine; human papillomavirus ID HUMAN PAPILLOMAVIRUS INFECTION; MEDIATED IMMUNE-RESPONSES; INTERFERON-GAMMA; HPV TYPE-16; INTRAEPITHELIAL NEOPLASIA; CELL-CLONES; E7 PROTEIN; ANTITUMOR; RISK; DNA AB Purpose. The ability to mount lymphoproliferative responses to peptides derived from the human papillomavirus (HPV) E6 and E7 oncoproteins has been associated with regression of dysplastic lesions of the uterine cervix and loss of associated HPV infection. Interleukin-12 (IL-12) is a potent immunopotentiator of T-cell function, and has been shown in phase I clinical trials to be tolerable. Experimental design. Patients were required to have measurable metastatic, recurrent or inoperable cervical carcinoma. Patients could have had one prior adjuvant regimen and one prior regimen for advanced disease. Treatment consisted of IL-12 administered at 250 ng/kg IV as a rapid push in the outpatient setting daily x5 every 21 days. Whole blood samples were acquired twice before treatment then approximately every 3 weeks to assess, lymphoproliferative response in vitro to HPV type 16 (HPV 16) E4, E6, and E7 peptides. These responses were correlated with demographics and with clinical outcome. Results. Thirty-four patients were enrolled; 29 were evaluable. Over half had received cisplatin-based chemotherapy. The most common serious toxicities were hematologic or hepatic, and all were reversible. There was one partial responder (3%). The median survival was 6.5 months (95% CI: 5.8, 11.5 months). Eighteen of 29 eligible patients had evaluable laboratory data both pre- and post-therapy. There was a statistically significant increase in lymphoproliferative responses for HPV 16 E4, E6, and E7 peptides (P = 0.020, 0.020, 0.043). There was a significant association between change in lymphoproliferative response to HPV 16 E6 peptides and number of cycles of treatment administered (P = 0.048). There was no correlation between change in lymphoproliferative response to any peptide with age, performance status, race, prior chemotherapy, time from diagnosis to treatment, or with overall survival. Conclusions. IL-12 treatment was associated with improved lymphoproliferative responses to HPV 16 E4, E6, and E7 peptides. This is the first clinical trial to demonstrate induction of cell-mediated immune (CMI) responses to specific antigens (peptides) following treatment with IL-12 in women with cervical cancer. This improvement in immune response was not associated with enhanced objective response or survival. (C) 2004 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Div Hematol & Oncol, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Colorado Canc Res Program CCOP, Denver, CO USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Wadler, S (reprint author), Cornell Univ, Weill Med Coll, Div Hematol & Oncol, C606,1300 York Ave, New York, NY 10021 USA. EM scw2004@med.cornell.edu FU NCI NIH HHS [CA21115, CA75405, CA14958, CA66636, CA23318, CA21076] NR 41 TC 29 Z9 31 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2004 VL 92 IS 3 BP 957 EP 964 DI 10.1016/j.ygyno.2003.12.022 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 800WF UT WOS:000220057700033 PM 14984966 ER PT J AU Tort, F Camacho, E Bosch, F Harris, NL Montserrat, E Campo, E AF Tort, F Camacho, E Bosch, F Harris, NL Montserrat, E Campo, E TI Familial lymphoid neoplasms in patients with mantle cell lymphoma SO HAEMATOLOGICA LA English DT Article DE mantle cell lymphoma; ATM; CHK2; CHK1; p53 ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; LI-FRAUMENI-SYNDROME; ATM MUTATIONS; DNA-DAMAGE; LYMPHOPROLIFERATIVE DISORDERS; ATAXIA-TELANGIECTASIA; AGGRESSIVE VARIANTS; PROTEIN EXPRESSION; BREAST-CANCER AB Background and Objectives. Familial aggregation has been recognized in patients with several lymphoid neoplasms, but the genetic basis for this familial clustering is not known. Germ-line mutations in the ataxia-telangiectasia mutated (ATM) and CHK2 genes have been detected in patients with mantle cell lymphoma (MCL), suggesting a potential role of these genes in genetic predisposition to these tumors. However, no familial association has been previously recognized in MCL. Design and Methods. To determine the possible existence of familial lymphoid neoplasms in MCL, we searched clinical records of MCL patients and identified three families in which a MCL, an acute B-cell lymphoblastic leukemia, and a lymphoplasmacytic lymphoma occurred in a first-degree relative of a MCL patient. Results. The neoplasms in two daughters appeared at an earlier age and were more aggressive than that in the respective parent, suggesting that the phenomenon of anticipation may characterize familial lymphomas associated with MCL. No mutations were detected in the ATM, CHK2, CHK1, and p53 genes. Interpretation and Conclusions. Our findings suggest that inactivation of the investigated DNA damage response genes do not account for familial disease aggregation in MCL patients, although such aggregation may occur and seems to be associated with the phenomenon of anticipation. C1 Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer, Hematopathol Unit,Lab Pathol,Dept Pathol, Barcelona 08036, Spain. Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer, Hematopathol Unit,Dept Hematol, Barcelona 08036, Spain. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Campo, E (reprint author), Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer, Hematopathol Unit,Lab Pathol,Dept Pathol, Villarroel 170 Esc 2 Pl 5, Barcelona 08036, Spain. EM campo@medicina.ub.es OI Bosch, Francesc/0000-0001-9241-2886; Campo, elias/0000-0001-9850-9793 NR 44 TC 11 Z9 11 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAR PY 2004 VL 89 IS 3 BP 314 EP 319 PG 6 WC Hematology SC Hematology GA 801VT UT WOS:000220124100012 PM 15020270 ER PT J AU Miovic, M AF Miovic, M TI An introduction to spiritual psychology: Overview of the literature, East and West SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article DE aurobindo; Buddhism; Eastern philosophy; mental health; psychotherapy; religion; spirituality; transpersonal psychology ID PARASUICIDAL BORDERLINE PATIENTS; STRESS REDUCTION PROGRAM; BEHAVIORAL TREATMENT; ANXIETY DISORDERS; FOLLOW-UP; PSYCHOTHERAPY; MEDITATION; PSYCHIATRY AB This article outlines the philosophical background to spiritual psychology and selectively reviews Western and Eastern literature on the subject. The world views of theism, atheism, and agnosticism are defined and critiqued, and the boundaries of scientific knowledge discussed. The views of James, Jung, and Freud are reviewed, and the contributions of humanistic psychology noted. Contemporary spiritual psychology is then summarized with reference to recent literature on theistic psychotherapy, Buddhist psychology, mind-body medicine, and transpersonal psychology. Sri Aurobindo's work is introduced as a modern Asian perspective on theistic psychology, and his model of the relationship between the "soul" and the unconscious described. Finally, a brief clinical vignette is given. C1 Harvard Univ, Sch Med, Dept Psychiat, Psychosocial Oncol Program,Dana Farber Canc Inst, Boston, MA USA. RP Miovic, M (reprint author), Dana Farber Canc Inst, G-420C,44 Binney St, Boston, MA 02115 USA. EM mmiovic@partners.org NR 73 TC 11 Z9 12 U1 3 U2 21 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2004 VL 12 IS 2 BP 105 EP 115 DI 10.1080/10673220490447209 PG 11 WC Psychiatry SC Psychiatry GA 817IN UT WOS:000221171300003 PM 15204805 ER PT J AU Krishnan, A Xu, YS Gandour, JT Cariani, PA AF Krishnan, A Xu, YS Gandour, JT Cariani, PA TI Human frequency-following response: representation of pitch contours in Chinese tones SO HEARING RESEARCH LA English DT Article DE time-variant pitch; voice pitch; phase-locking; autocorrelation; speech prosody; Chinese tones ID VENTRAL COCHLEAR NUCLEUS; AUDITORY-NERVE FIBERS; STEADY-STATE VOWELS; DISCHARGE PATTERNS; COMPLEX TONES; 2-TONE APPROXIMATIONS; PERIODIC PULSES; PERCEPTION; SPEECH; SOUNDS AB Auditory nerve single-unit population studies have demonstrated that phase-locking plays a dominant role in the neural encoding of both the spectrum and voice pitch of speech sounds. Phase-locked neural activity underlying the scalp-recorded human frequency-following response (FFR) has also been shown to encode certain spectral features of steady-state and time-variant speech sounds as well as pitch of several complex sounds that produce time-invariant pitch percepts. By extension, it was hypothesized that the human FFR may preserve pitch-relevant information for speech sounds that elicit time-variant as well as steady-state pitch percepts. FFRs were elicited in response to the four lexical tones of Mandarin Chinese as well as to a complex auditory stimulus which was spectrally different but equivalent in fundamental frequency (f(0)) contour to one of the Chinese tones. Autocorrelation-based pitch extraction measures revealed that the FFR does indeed preserve pitch-relevant information for all stimuli. Phase-locked interpeak intervals closely followed f(0). Spectrally different stimuli that were equivalent in F-0 similarly showed robust interpeak intervals that followed f(0). These FFR findings support the viability of early, population-based 'predominant interval' representations of pitch in the auditory brainstem that are based on temporal patterns of phase-locked neural activity. (C) 2004 Elsevier B.V. All rights reserved. C1 Purdue Univ, Dept Audiol & Speech Sci, Auditory Electrophysiol Lab, W Lafayette, IN 47907 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Krishnan, A (reprint author), Purdue Univ, Dept Audiol & Speech Sci, Auditory Electrophysiol Lab, 1353 Heavilon Hall,500 Oval Dr, W Lafayette, IN 47907 USA. EM rkrish@purdue.edu FU NIDCD NIH HHS [R01 DC04584-04] NR 72 TC 78 Z9 83 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2004 VL 189 IS 1-2 BP 1 EP 12 DI 10.1016/S0378-5955(03)00402-7 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 801VP UT WOS:000220123700001 PM 14987747 ER PT J AU El-Serag, HB Davila, JA AF El-Serag, HB Davila, JA TI Is fibrolamellar carcinoma different from hepatocellular carcinoma? A US population-based study SO HEPATOLOGY LA English DT Article ID NATURAL-HISTORY; CHILDHOOD; HEPATOMA; CHILDREN AB There have been no population-based studies of the epidemiology and prognosis of patients with fibrolamellar carcinoma (FLC). We conducted a retrospective cohort study using information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program. The demographic features, stage at diagnosis, and type of therapy, as well as age-adjusted incidence rates and observed and relative survival rates were compared between persons with FLC and those with hepatocellular carcinoma (HCC) diagnosed between 1986 and 1999. A multivariate Cox proportional hazards model was constructed to examine the effect of histology (FLC vs. HCC) on the risk of mortality. There were 68 microscopically confirmed cases of FLC and 7,896 cases of HCC. FLC constituted 0.85% of all cases of primary liver cancer and 13.4% of all cases below the age of 40. Compared to HCC, patients with FLC were more likely to be younger (mean age 39 vs. 65), female (51.5% vs. 26.3%), and white (85.3% vs. 56.9%). A greater proportion of case with FLC had localized disease (41.2% vs. 30.9%), or received potentially curative therapy (resection, transplantation), compared to cases with HCC. The age-adjusted incidence rate for FLC was 0.02 per 100,000; No significant differences in age-adjusted incidence rates were observed by gender or race. The 1- and 5-year observed and relative survival rates were significantly longer in patients with FLC than HCC. The 5-year relative survival rate was 31.8% (95% CI, 20.5%-43.1%) for FLC, compared with 6.8% (95% CI, 6.3%-7.4%) for HCC. Adjusting for differences in age, gender, race, stage of disease, receipt of resection or transplantation, and time of diagnosis, FLC was independently associated with a 46% reduction in risk of mortality within 5years compared with HCC. In conclusion, in a population-based study, we observed remarkable differences in the epidemiology and prognosis of FLC compared to HCC. C1 Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 14 TC 94 Z9 101 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2004 VL 39 IS 3 BP 798 EP 803 DI 10.1002/hep.20096 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 806IP UT WOS:000220427900027 PM 14999699 ER PT J AU Jefferson, JA Simon, J Escudero, E Hurtado, ME Swenson, ER Wesson, DE Schreiner, GF Schoene, RB Fohnson, RJ Hurtado, A AF Jefferson, JA Simon, J Escudero, E Hurtado, ME Swenson, ER Wesson, DE Schreiner, GF Schoene, RB Fohnson, RJ Hurtado, A TI Increased oxidative stress following acute and chronic high altitude exposure SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE reactive oxygen species; lipid peroxidation; F-2-isoprostane; chronic mountain sickness; acute mountain sickness ID CHRONIC MOUNTAIN-SICKNESS; MODERATE-ALTITUDE; LIPID-PEROXIDATION; ANTIOXIDANT ENZYMES; REACTIVE OXYGEN; GLUTATHIONE DISULFIDE; HYPOBARIC HYPOXIA; VITAMIN-E; IN-VIVO; HUMANS AB Jefferson, J. Ashley, Jan Simoni, Elizabeth Escudero, Maria-Elena Hurtado, Erik R. Swenson, Donald E. Wesson, George F. Schreiner, Robert B. Schoene, Richard J. Johnson, Abdias Hurtado. Increased oxidative stress following acute and chronic high altitude exposure. High Alt. Med. Biol. 5:61-69, 2004.-The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F-2-isoprostane, 8-iso PGF(2alpha) (1.31 +/- 0.8 mug/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 mumol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, P = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2alpha) (1.3 +/- 0.8 mug/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 mumol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high attitude without exercise and with chronic residence at high altitude. C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Texas Tech Univ, Dept Surg, Lubbock, TX 79409 USA. Univ Peruana Cayetano Heredia, Hosp Loayza, Nephrol Ctr, Lima, Peru. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Texas Tech Univ, Dept Internal Med, Lubbock, TX 79409 USA. Scios Inc, Sunnyvale, CA USA. Univ Washington, Providence Med Ctr, Seattle, WA 98195 USA. Baylor Coll Med, Renal Sect, Houston, TX 77030 USA. RP Jefferson, JA (reprint author), Univ Washington, Div Nephrol, Box 356521,1959 Pacific Ave, Seattle, WA 98195 USA. EM jashleyj@u.washington.edu NR 42 TC 67 Z9 71 U1 1 U2 12 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SPR PY 2004 VL 5 IS 1 BP 61 EP 69 DI 10.1089/152702904322963690 PG 9 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 812WL UT WOS:000220869500007 PM 15072717 ER PT J AU Firth, PG Bolay, H AF Firth, PG Bolay, H TI Transient high altitude neurological dysfunction: An origin in the temporoparietal cortex SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE hallucination; high altitude; high altitude cerebral edema; high altitude pulmonary edema; hypoxia; migraine; seizure ID LOBE EPILEPSY; EXPERIENCES; PERCEPTION; PARIETAL; APRAXIA; SYSTEM; BRAIN AB Firth, Paul G., Hayrunnisa Bolay. Transient high altitude neurological dysfunction: An origin in the temporoparietal cortex. High Alt. Med. Biol. 5:71-75, 2004.-This case report describes three separate episodes of isolated ataxia, hallucinations of being accompanied by another person, and bilateral dressing apraxia occurring in a single individual without prior warning signs. These symptoms are attributable to disruption of vestibular processing in the temporoparietal cortex or associated limbic structures. Neurological dysfunction at high altitude is usually ascribed to high altitude cerebral edema or acute mountain sickness. However, transient neurological symptoms occur abruptly at more extreme altitudes, often following vigorous exertion, without overt altitude-induced prodromes. These symptoms may be caused by intense neuronal discharge or neuronal synchronization as a feature of epileptic discharges or cortical spreading depression. Transient high altitude neurological dysfunction should be recognized as a separate complication of extreme altitude, distinct from high altitude cerebral edema. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Gazi Univ, Dept Neurol, Ankara, Turkey. RP Firth, PG (reprint author), John Radcliffe Hosp, Nuffield Dept Anaesthet, Oxford OX3 9DU, England. EM pfirth@partners.org NR 32 TC 11 Z9 14 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD SPR PY 2004 VL 5 IS 1 BP 71 EP 75 DI 10.1089/152702904322963708 PG 5 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 812WL UT WOS:000220869500008 PM 15072718 ER PT J AU Couto, L Parker, A Gordon, JW AF Couto, L Parker, A Gordon, JW TI Direct exposure of mouse spermatozoa to very high concentrations of a serotype-2 adeno-associated virus gene therapy vector fails to lead to germ cell transduction SO HUMAN GENE THERAPY LA English DT Article ID RECOMBINANT AAV-2 VECTOR; THYMIDINE KINASE GENE; HEMOPHILIA-B DOGS; GANCICLOVIR THERAPY; FACTOR-IX; ADENOVIRUS; EXPRESSION; INJECTION; DNA; BIODISTRIBUTION AB In a clinical safety trial involving an adeno-associated virus (AAV) gene therapy vector encoding human factor IX, intrahepatic administration of the vector was associated with the finding of vector DNA in semen that persisted for several weeks. Uncertainty remains as to the route by which the vector reached semen, but the finding raised the prospect that mature sperm could be exposed to the vector and sustain integration of vector DNA. To provocatively test for the ability of AAV vectors to transduce mature sperm, we exposed mouse sperm to concentrations of the same vector used in clinical studies at concentrations ranging from 840 to 3400 particles per sperm cell, performed in vitro fertilization and embryo transfer, and evaluated newborn pups by Southern analysis for the presence of vector sequences. Of 102 pups analyzed, none showed evidence of vector DNA integration. We conclude from these studies that exposure of mature sperm to AAV gene therapy vectors is highly unlikely to lead to germline transduction. C1 Avigen Inc, Alameda, CA 94502 USA. CUNY Mt Sinai Sch Med, Dept Obstet Gynecol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. RP Gordon, JW (reprint author), Bronx Vet Adm Med Ctr, Res Bldg,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Jon.Gordon@mssm.edu NR 26 TC 20 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2004 VL 15 IS 3 BP 287 EP 291 DI 10.1089/104303404322886138 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 803DZ UT WOS:000220213100006 PM 15018737 ER PT J AU Ruiz-Morales, JA Vargas-Alarcon, G Flores-Villanueva, PO Villarreal-Garza, C Hernandez-Pacheco, G Yamamoto-Furusho, JK Rodriguez-Perez, JM Perez-Hernandez, N Rull, M Cardiel, MH Granados, J AF Ruiz-Morales, JA Vargas-Alarcon, G Flores-Villanueva, PO Villarreal-Garza, C Hernandez-Pacheco, G Yamamoto-Furusho, JK Rodriguez-Perez, JM Perez-Hernandez, N Rull, M Cardiel, MH Granados, J TI HLA-DRB1 alleles encoding the "Shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican mestizos SO HUMAN IMMUNOLOGY LA English DT Article ID HLA-DR; EXTRAARTICULAR MANIFESTATIONS; GENE-FREQUENCIES; ADMIXTURE; REGION; DRB1-ASTERISK-0405; EXPRESSION; POPULATION; DISABILITY; HLA-DQA1 AB The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences inproportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRBI allele encoding the SE was significantly increased in RA cases as compared to controls (pc = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE + cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF. (C) American Society for Histocompatibility and Immunogenetics, 2004. Published by Elsevier Inc. C1 Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Mexico City 14000, DF, Mexico. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Inst Nacl Cardiol, Cellular Sect Biol, Dept Physiol, Ignacio Chavez, Mexico City, DF, Mexico. RP Granados, J (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Immunol & Rheumatol, Vasco Quiroga 15, Mexico City 14000, DF, Mexico. EM julgrate@yahoo.com NR 35 TC 22 Z9 29 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 2004 VL 65 IS 3 BP 262 EP 269 DI 10.1016/j.humimm.2003.12.009 PG 8 WC Immunology SC Immunology GA 810DT UT WOS:000220685700010 PM 15041166 ER PT J AU Sutovsky, P Hauser, R Sutovsky, M AF Sutovsky, P Hauser, R Sutovsky, M TI Increased levels of sperm ubiquitin correlate with semen quality in men from an andrology laboratory clinic population SO HUMAN REPRODUCTION LA English DT Article DE male infertility; sperm; SUTI assay; toxicology; ubiquitin ID RAT EPIDIDYMIS; GENE-EXPRESSION; SEMINAL PLASMA; FERTILIZATION; SPERMATOZOA; MORPHOLOGY; INFERTILITY; PROTEIN; IMMUNOREACTIVITIES; PROTEOLYSIS AB Background: Ubiquitin, a house-keeping protein that marks other proteins for proteasomal degradation, tags defective sperm during epididymal passage. To establish ubiquitin as a biomarker of human infertility, the present study examines the relationships between sperm ubiquitin content and clinical semen parameters among men from an infertility clinic population with varied aetiologies. Methods: Anti-ubiquitin immunoreactivity was measured by flow cytometric sperm-ubiquitin tag immunoassay (SUTI) in sperm samples of 28 infertility patients and 15 fertile donors. Semen analyses were performed by computer-assisted semen analysis and World Health Organization morphology. Results: Median values of ubiquitin-induced fluorescence had a strong negative correlation with sperm count (r=-0.63, P=0.0003) and a positive correlation with % abnormal morphology (r=0.55, P=0.01). Infertility patients (n=28) had significantly higher levels of sperm ubiquitin. Out of 28 patients, six reported possible occupational exposures to solvents, three were current smokers and six were ex-smokers. Within the patient group, men with known male factor infertility, those with self-reported occupational exposure to solvents and current smokers had the highest sperm ubiquitin levels. When men with jobs involving potential occupational exposure to solvents were combined with current smokers, the highest correlations were found between sperm ubiquitin and motility (r=-0.74), count (r=-0.82) and % sperm abnormalities (r=0.73).Conclusions: Increased sperm ubiquitin was inversely associated with sperm count, motility and % normal morphology, supporting the use of ubiquitin as a biomarker of human semen quality. SUTI assay confirmed poor semen quality in all men with poor clinical semen parameters, but also was high in some patients with seemingly good clinical semen parameters. Occupational exposure to solvents and smoking may have contributed to high levels of sperm ubiquitin in some of these patients. C1 Univ Missouri, Dept Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Obstet & Gynecol, Columbia, MO 65211 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. RP Sutovsky, P (reprint author), Univ Missouri, Dept Anim Sci, S141 ASRC,920 E Campus Dr, Columbia, MO 65211 USA. EM SutovskyP@missouri.edu FU NIEHS NIH HHS [ES09718]; NIOSH CDC HHS [OH07324-01] NR 45 TC 40 Z9 40 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 2004 VL 19 IS 3 BP 628 EP 638 DI 10.1093/humrep/deh131 PG 11 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 801CO UT WOS:000220074200027 PM 14998962 ER PT J AU Goodfriend, TL Calhoun, DA AF Goodfriend, TL Calhoun, DA TI Resistant hypertension, obesity, sleep apnea, and aldosterone - Theory and therapy SO HYPERTENSION LA English DT Article DE obesity; aldosterone; sleep apnea; hypertension; fatty acids; renin ID CHRONIC EPISODIC HYPOXIA; BLOOD-PRESSURE; INSULIN-RESISTANCE; SYMPATHETIC ACTIVITY; RENIN-ACTIVITY; HEART-FAILURE; SPIRONOLACTONE; MORBIDITY; PLASMA; MECHANISMS AB Hypertension resistant to 2 antihypertensive drugs is more common among obese patients than among lean patients. The case we describe and the observations we report suggest that refractoriness among obese hypertensives is frequently caused by obstructive sleep apnea and/or inappropriately high plasma aldosterone levels. In other words, obese hypertensives may have sleep apnea, obese hypertensives without sleep apnea may have inappropriately elevated levels of plasma aldosterone, and a surprising number of obese patients with sleep apnea also have elevated levels of aldosterone. The mechanisms by which obesity and obstructive sleep apnea increase aldosterone levels and raise blood pressure are not understood, but sympathetic nervous system activation and production of nonclassical adrenal stimuli are two possibilities. Obstructive sleep apnea can be detected with a careful history and various sleep studies. Inappropriately elevated aldosterone levels can be detected by measuring the ratio of plasma aldosterone concentration to plasma renin activity. Successful treatment of these resistant hypertensives often can be achieved by devices that provide positive pressure to the upper airway to correct obstructive sleep apnea and by incorporating an aldosterone antagonist in the therapeutic regimen. C1 William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Univ Alabama, Vasc Biol & Hypertens Program, Birmingham, AL USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Res Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. EM tgoodfri@facstaff.wisc.edu NR 59 TC 139 Z9 163 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2004 VL 43 IS 3 BP 518 EP 524 DI 10.1161/01.HYP.0000116223.97436.e5 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 778LR UT WOS:000189243500001 PM 14732721 ER PT J AU Kulkarni, RN AF Kulkarni, RN TI The islet beta-cell SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE beta-cell; insulin; IGF-1; IGF-1 receptor; islet; Langerhans ID INSULIN GENE-TRANSCRIPTION; ACTIVATED PROTEIN-KINASE; PANCREATIC LINEAGE; MICE; RECEPTOR; GLUCOSE; SECRETION; EXPRESSION; ENDOCRINE; GROWTH AB The beta-cell is one of four major types of cells present in the islets of Langerhans, which are islands of cells distributed throughout the endocrine pancreas in most mammals. The beta-cell synthesizes and secretes the hormone insulin mainly in response to glucose but also in response to several nutrients, hormones and nervous stimuli. In adult rodents the beta-cell has a slow mitotic rate. Recent studies provide novel insights into the functions of the beta-cell. The presence of functional insulin-like growth factor-1 and insulin receptors and components of their signaling pathway indicate an important role for insulin/IGF-1 signaling in the regulation of beta-cell function. Further, the recent discovery of glucokinase (GK) and the ATP-dependent potassium channels on insulin secretory granules, the detection of AMP-protein kinase in the beta-cell and the identification of a new beta-cell transcription factor, mMafA, are some exciting new areas of research currently underway to further understand the complex pathways that regulate the functions of beta-cells. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@jostin.harvard.edu NR 28 TC 39 Z9 42 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD MAR PY 2004 VL 36 IS 3 BP 365 EP 371 DI 10.1016/j.biocel.2003.08.010 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 836EE UT WOS:000222537400001 PM 14687913 ER PT J AU Aepfelbacher, FC Yeon, SB Weinrauch, LA D'Elia, J Burger, AJ AF Aepfelbacher, FC Yeon, SB Weinrauch, LA D'Elia, J Burger, AJ TI Improved glycemic control induces regression of left ventricular mass in patients with type 1 diabetes mellitus SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE diabetes mellitus; left ventricular hypertrophy; echocardiography; glycemic control ID HEART-DISEASE; CARDIOMYOPATHY; HYPERTENSION; HYPERTROPHY; FRAMINGHAM; FEATURES; CALCIUM AB Background: Diabetes mellitus has been associated with abnormalities of cardiac function and left ventricular hypertrophy. We sought to determine whether improved glycemic control in patients with type 1 diabetes mellitus will induce reversal of those abnormalities. Methods: We prospectively studied 19 patients (mean age 40 +/- 9 years) with longstanding type 1 diabetes mellitus (28 +/- 4 years), who participated in a program of stringent glycemic control. Glycemic control was monitored with hemoglobin A1c levels, and improvement was defined as >1% (absolute) decrease of hemoglobin A1c. Two-dimensional and Doppler echocardiograms and ambulatory 24-h blood pressures were obtained at baseline and after 1 year. Left ventricular mass was determined using the area-length method. Results: In the patients with improved glycemic control (n = 12), hemoglobin A1c decreased from 9.8% to 7.8% (p less than or equal to 0.0001), interventricular septal thickness decreased from 10.3 to 9.4 mm (p less than or equal to 0.05), and left ventricular mass regressed from 205 to 182 g (p less than or equal to 0.05). Septal thickness and left ventricular mass remained unchanged in the patients who did not achieve improvement of glycemic control. Left ventricular internal diameters, posterior wall thickness, fractional shortening, E/A ratio of mitral inflow, E-wave deceleration time (DT), and ambulatory 24-h blood pressures did not change significantly after I year in either group. Conclusions: Improved glycemic control in patients with type I diabetes mellitus is associated with regression of septal thickness and left ventricular mass without significant effect on systolic or diastolic function, in the absence of significant alterations in ambulatory 24-h blood pressures. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Div Cardiovasc, Noninvas Cardiol Lab, Boston, MA 02215 USA. Mt Auburn Hosp, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Burger, AJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, Noninvas Cardiol Lab, Baker 3,1 Deaconess Rd, Boston, MA 02215 USA. OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 25 TC 17 Z9 21 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR PY 2004 VL 94 IS 1 BP 47 EP 51 DI 10.1016/j.ijcard.2003.04.012 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803VP UT WOS:000220258900008 PM 14996474 ER PT J AU Lechpammer, M Lukac, J Lechpammer, S Kovacevic, D Loda, M Kusic, Z AF Lechpammer, M Lukac, J Lechpammer, S Kovacevic, D Loda, M Kusic, Z TI Humoral immune response to p53 correlates with clinical course in colorectal cancer patients during adjuvant chemotherapy SO INTERNATIONAL JOURNAL OF COLORECTAL DISEASE LA English DT Article DE colorectal cancer; tumor suppressor gene p53; serum p53 antibodies; cancer treatment; follow-up ID PROGNOSTIC-SIGNIFICANCE; ANTI-P53 ANTIBODIES; SERUM ANTIBODIES; POOR-PROGNOSIS; MUTATIONS; PROTEIN; GENE; AUTOANTIBODIES; CARCINOMAS; EXPRESSION AB Background and aims. Overexpression of p53 protein in malignancies induces an immune response in some cancer patients. We investigated whether production of serum antibodies against p53 (p53-Ab) is associated with pathohistological parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker during cancer treatment. Patients and methods. Serum samples from 220 colorectal cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in tumors was determined using mouse anti-human p53-Ab.Results. Serum p53-Ab were detected in 18% of patients while all controls were negative. A strong correlation between p53-Ab production and p53 protein expression was observed: 70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab negative cases. There was also a significant predominance of p53-Ab positive cases in Dukes' stages B and C over stage A. Although surgery alone reduced p53-Ab levels, decreases in p53-Ab titer became significant midterm through chemotherapy compared to both pre- and postoperative values and remained decreased until the completion of treatment.Conclusion. The presence of p53-Ab in sera of patients with colorectal cancer indicates tumors in more advanced histopathologic stages (Dukes' B, C). Due to low sensitivity (18%) p53-Ab are not recommendable as a preoperative marker for colorectal cancer. However, due to high specificity (100%), their monitoring after surgery and adjuvant chemotherapy has potential for early diagnosis of tumor relapse in p53-Ab positive cases. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp Sestre Milosrdnice, Dept Surg, Zagreb 10000, Croatia. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lechpammer, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM mirna_lechpammer@dfci.harvard.edu NR 27 TC 30 Z9 35 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-1958 J9 INT J COLORECTAL DIS JI Int. J. Colorectal Dis. PD MAR PY 2004 VL 19 IS 2 BP 114 EP 120 DI 10.1007/s00384-003-0553-5 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 769VF UT WOS:000188669900006 PM 14634775 ER PT J AU Koontz, AM Cooper, RA Boninger, ML Souza, AL Fay, BT AF Koontz, AM Cooper, RA Boninger, ML Souza, AL Fay, BT TI Scapular range of motion in a quasi-wheelchair push SO INTERNATIONAL JOURNAL OF INDUSTRIAL ERGONOMICS LA English DT Article; Proceedings Paper CT Workshop on Anthropometry and Disability CY 2001 CL Buffalo, NY SP NIDRR, Access Board DE shoulder; wheelchair propulsion; biomechanics; kinematics; scapular motion ID UPPER EXTREMITY; SHOULDER PAIN; KINEMATICS; POSITION; IMPINGEMENT; PROPULSION; BIOMECHANICS; ORIENTATION; ASSOCIATION; MECHANISM AB Descriptions of shoulder kinematics during wheelchair propulsion are limited to motions of the upper arm due to the difficulty of measuring scapular movement in vivo. Using a digitizing stylus, the three-dimensional positions of three anatomical landmark's on the scapula were recorded for 10 manual wheelchair users in six different statically held hand positions (-30degrees, -15degrees, 0degrees, 15degrees, 30degrees, 60degrees) on the pushrim. In each hand position, a motion analysis system recorded the coordinates of infrared markers on the arm and torso. Scapular, humeral, and torso angles were computed using an Euler angle decomposition method for each position relative to the torso. At the beginning of the push, the scapula was rotated slightly upward (1.5degrees), minimally protracted (15degrees), and maximally tipped forward (22degrees). In addition, the humerus was maximally extended, abducted and internally rotated. As subjects moved forward along the pushrim, the protraction angle increased while the forward tipping angle decreased. The humerus became increasingly more flexed as the push progressed with small changes observed in humeral abduction and internal rotation. A stepwise multiple regression analysis procedure (p<0.01) revealed that the torso, humeral flexion/extension and abduction angles are good predictors for estimating forward tipping and upward/downward rotation of the scapula. The regression equations enable researchers to estimate scapular orientation during propulsion which could provide further insight into specific biomechanical factors that lead to shoulder pathology. C1 Vet Affairs Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA. RP Koontz, AM (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Human Engn Res Labs, 7180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. EM akoontz@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 36 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-8141 J9 INT J IND ERGONOM JI Int. J. Ind. Ergon. PD MAR PY 2004 VL 33 IS 3 BP 237 EP 248 DI 10.1016/j.ergon.2003.04.002 PG 12 WC Engineering, Industrial; Ergonomics SC Engineering GA 778NW UT WOS:000189248500007 ER PT J AU Biederman, J Spencer, T Wilens, T AF Biederman, J Spencer, T Wilens, T TI Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE atomoxetine; attention-deficit hyperactivity disorder; pharmacotherapy; psychostimulants; tricyclic antidepressants ID PRELIMINARY CLINICAL-EXPERIENCE; ONCE-A-DAY; DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; TOURETTES-SYNDROME; TIC DISORDER; CIGARETTE-SMOKING; CONTROLLED-TRIAL; METHYLPHENIDATE TREATMENT; CHILDHOOD HYPERACTIVITY AB There is a substantial body of literature documenting the efficacy of multiple unrelated pharmacological agents in attention-deficit hyperactivity disorder (ADHD) individuals throughout the life-cycle. The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. The literature documents that stimulants not only improve abnormal behaviours of ADHD, but also improves self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbidities. In addition there is a large body of literature documenting the efficacy of atomoxetine which shows improvement in these same domains. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-aged Caucasian boys. Further, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. EM Biederman@helix.mgh.harvard.edu FU NICHD NIH HHS [2R01HD036317-06, 5R01HD36317-05]; NIMH NIH HHS [5R29MH575105, 5R01MH50657-10] NR 159 TC 102 Z9 106 U1 9 U2 16 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD MAR PY 2004 VL 7 IS 1 BP 77 EP 97 DI 10.1017/S1461145703003973 PG 21 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 816GG UT WOS:000221097800011 PM 14733627 ER PT J AU Hilsenroth, MJ Baity, MR Mooney, MA Meyer, GJ AF Hilsenroth, MJ Baity, MR Mooney, MA Meyer, GJ TI DSM-IV Major Depressive Episode criteria: An evaluation of reliability and validity across three different rating methods SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN CLINICAL PRACTICE LA English DT Article DE depression; assessment; DSM-IV; reliability ID BEHAVIORAL-DISORDERS; FIELD TRIAL; MENTAL-DISORDERS; COMMON LANGUAGE; MOOD DISORDERS; AXIS II; PSYCHIATRY; DIAGNOSIS; SYMPTOMS; ICD-10 AB This study examined the reliability and validity of the DSM-IV Major Depressive Episode (MDE) symptoms in a sample of outpatients based on clinician ratings of assessment interviews, videotape of these interviews, and chart information. A group of 44 patients admitted to a university based outpatient community clinic were rated by trained clinicians on the nine MDE symptom criteria (A1-A9). Patients also completed a self-report measure of depressive symptomatology. Interrater reliability was found to be highest between the interview and videotape ratings. Conversely, when comparing chart ratings with those made from either interview or videotape, reliability for many of the individual criteria were found to be in the poor range of reliability. Good internal consistency was found for both the interview and videotape ratings, while internal consistency was less adequate for chart-based ratings. However, the three MDE ratings converge on a single dimension in a similar manner regardless of which source (i.e. interview, videotape, or chart) provided the rating. Additional analyses revealed a consistent relationship between the three MDE ratings (interview, videotape, and chart) with measures of patient reported depressive symptoms that exceeded the relationship between these scores with global levels/severity of psychopathology. The effects of longer interviews as well as examining depressive symptoms within the context of interpersonal functioning is discussed regarding the reliable assessment of depressive symptomatology in the mild to moderate range of severity. C1 Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Univ Toledo, Dept Psychol, Toledo, OH 43606 USA. RP Hilsenroth, MJ (reprint author), Adelphi Univ, Derner Inst Adv Psychol Studies, Garden City, NY 11530 USA. EM hilsenro@adelphi.edu NR 31 TC 7 Z9 7 U1 2 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1365-1501 J9 INT J PSYCHIAT CLIN JI Int. J. Psychiat. Clin. PD MAR PY 2004 VL 8 IS 1 BP 3 EP 10 DI 10.1080/13651500310004795 PG 8 WC Psychiatry SC Psychiatry GA 803PD UT WOS:000220242100002 PM 24937577 ER PT J AU Siegle, GJ Steinhauer, SR Thase, ME AF Siegle, GJ Steinhauer, SR Thase, ME TI Pupillary assessment and computational modeling of the Stroop task in depression SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 11th World Congress of Psychophysiology CY 2002 CL Montreal, CANADA DE depression; neural network; stroop; interference; pupil dilation; attention ID MAJOR DEPRESSION; EMOTIONAL INFORMATION; RESPONSES; ABNORMALITIES; DYSFUNCTION; PERFORMANCE; METABOLISM; ATTENTION; REDUCTION; DISORDER AB Depressed individuals frequently display disruptions in selective attention, but the time course and specificity of these difficulties are not well-understood. To better understand the nature of attentional disruptions in depression, 28 healthy adults and 23 unmedicated depressed adults completed a Stroop color-naming task using a long inter-stimulus interval and pupil dilation was recorded as a measure of cognitive load. Both groups took longer to name the color for incongruent than congruent trials. Pupil dilation was also larger for incongruent trials than for congruent trials across groups. which suggested that pupil dilation reflected cognitive load on the task. Though the groups did not differ in the magnitude of Stroop effect in pupil dilation, depressed individuals displayed decreased pupil dilation in the seconds following stimuli relative to controls. Computational neural network modeling further suggested that observed effects were consistent with decreased prefrontal cortex activity, associated with decreased cognitive control. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Siegle, GJ (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, 3811 O Hara St, Pittsburgh, PA 15213 USA. EM gsiegle+@pitt.edu FU NIMH NIH HHS [MH55762, MH60473, MH64159] NR 37 TC 70 Z9 72 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD MAR PY 2004 VL 52 IS 1 BP 63 EP 76 DI 10.1016/j.ijpsycho.2003.12.010 PG 14 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 806GW UT WOS:000220423400006 PM 15003373 ER PT J AU Steinhauer, SR Siegle, GJ Condray, R Pless, M AF Steinhauer, SR Siegle, GJ Condray, R Pless, M TI Sympathetic and parasympathetic innervation of pupillary dilation during sustained processing SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 11th World Congress of Psychophysiology CY 2002 CL Montreal, CANADA DE pupillary dilation; sustained processing; sympathetic and parasympathetic pathways; pharmacology ID RESPONSES; REFLEX; PERFORMANCE; LOAD AB The contributions of separate sympathetic and parasympathetic pathways to pupillary dilation during a sustained processing task were studied through environmental and pharmacological manipulations. In Experiment 1, 22 healthy volunteers (11 female) performed a serial Subtract 7 task while pupil diameter was recorded both during moderate room light and in darkness. In a control for verbalization, subjects performed an easier Add I task. In all conditions, pupil diameter increased significantly during the response period as compared to a pre-verbalization baseline period. Pupillary dilation was increased for the difficult task, and further increase in dilation was associated with recording in light. This suggests a major differential contribution to task difficulty mediated through inhibition of the parasympathetic pathway. In Experiment 2, a subgroup of 12 volunteers (seven female) repeated all conditions at three additional sessions in which one eye was instilled with tropicamide (to block the parasympathetic sphincter muscle), dapiprazole (to block the sympathetic dilator muscle) or placebo. All pharmacological conditions resulted in overall dilation during task performance. Differential performance similar to the placebo condition was seen only in the dapiprazole condition, when parasympathetic activation was intact. The findings suggest that sustained performance during a difficult task is modulated by cortical inhibition of the parasympathetic pathway at the oculomotor nucleus. Moreover, modulation of both ambient light intensity and pharmacological blockade of the final pupillary musculature were observed to provide converging approaches for quantifying the activity of identifiable central autonomic pathways. (C) 2003 Elsevier B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Biometr Res Program, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA USA. RP Steinhauer, SR (reprint author), VA Pittsburgh Healthcare Syst, Biometr Res Program, 7180 Highland Dr,151R, Pittsburgh, PA 15206 USA. EM sthauer@pitt.edu FU NIMH NIH HHS [MH55762] NR 19 TC 117 Z9 121 U1 3 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD MAR PY 2004 VL 52 IS 1 BP 77 EP 86 DI 10.1016/j.ijpsycho.2003.12.005 PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 806GW UT WOS:000220423400007 PM 15003374 ER PT J AU St Clair, WH Adams, JA Bues, M Fullerton, BC La Shell, S Kooy, HM Loeffler, JS Tarbell, NJ AF St Clair, WH Adams, JA Bues, M Fullerton, BC La Shell, S Kooy, HM Loeffler, JS Tarbell, NJ TI Advantage of protons compared to conventional X-ray or IMRT in the treatment of a pediatric patient with medulloblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE medulloblastoma; proton; IMRT ID PRIMITIVE NEUROECTODERMAL TUMORS; CONFORMAL RADIOTHERAPY; INTRACRANIAL TUMORS; CRANIOSPINAL IRRADIATION; ADJUVANT CHEMOTHERAPY; SPINAL IRRADIATION; RADIATION-THERAPY; POTENTIAL ROLE; ONCOLOGY-GROUP; BRAIN-TUMORS AB Purpose: To compare treatment plans from standard photon therapy to intensity modulated X-rays (IMRT) and protons for craniospinal axis irradiation and posterior fossa boost in a patient with medulloblastoma. Methods: Proton planning was accomplished using an in-house 3D planning system. IMRT plans were developed using the KonRad treatment planning system with 6-MV photons. Results: Substantial normal-tissue dose sparing was realized with IMRT and proton treatment of the posterior fossa and spinal column. For example, the dose to 90% of the cochlea was reduced from 101.2% of the prescribed posterior fossa boost dose from conventional X-rays to 33.4% and 2.4% from IMRT and protons, respectively. Dose to 50% of the heart volume was reduced from 72.2% for conventional X-rays to 29.5% for IMRT and 0.5% for protons. Long-term toxicity with emphasis on hearing and endocrine and cardiac function should be substantially improved secondary to nontarget tissue sparing achieved with protons. Conclusion: The present study clearly demonstrates the advantage of conformal radiation methods for the treatment of posterior fossa and spinal column in children with medulloblastoma, when compared to conventional X-rays. Of the two conformal treatment methods evaluated, protons were found to be superior to IMRT. (C) 2004 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Tarbell, NJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM ntarbell@partners.org FU NCI NIH HHS [P01-CA 21239] NR 37 TC 144 Z9 145 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2004 VL 58 IS 3 BP 727 EP 734 DI 10.1016/S0360-3016(03)01574-8 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 773QP UT WOS:000188934600011 PM 14967427 ER PT J AU Chakravarti, A Dicker, A Mehta, M AF Chakravarti, A Dicker, A Mehta, M TI The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: A review of preclinical and correlative clinical data SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Symposium on Epidermal Growth Factor Receptor Inhibitors and Cancer Therapeutics CY JUN 04, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Radiat Therapy Oncol Grp, AstraZeneca Phamaceut, Bristrol-Meyers Squibb/Imclone Syst, Genentech, Novartis Oncol, Abgenix/Amgen, Wyeth Oncol DE EGFR; gliomas; radiation ID HUMAN GLIOBLASTOMA CELLS; FARNESYL TRANSFERASE INHIBITORS; MALIGNANT GLIOMA; MEDIATES RESISTANCE; HUMAN ASTROCYTOMAS; RAS ACTIVATION; MICE LACKING; HUMAN CANCER; EXPRESSION; OVEREXPRESSION AB Purpose: The epidermal growth factor receptor (EGFR) pathway is frequently upregulated in high-grade gliomas via gene amplification and by specific mutations that render EGFR constitutively active (EGFRvIII). Methods and Materials: This review highlights EGFR's role in mediating radiation resistance in gliomas: underlying molecular mechanisms, with discussion of relevant preclinical and clinical correlative data. Results: Preclinical and emerging clinical data suggest that EGFR signaling plays a potentially important role in mediating radiation resistance in human gliomas. Conclusions: Targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of glioma patients. (C) 2004 Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Univ Wisconsin, Med Ctr, Dept Radiat Oncol, Madison, WI 53706 USA. RP Chakravarti, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Founders House,Room 536, Boston, MA 02114 USA. EM achakravarti@partners.org OI Dicker, Adam/0000-0003-0733-3337; mehta, minesh/0000-0002-4812-5713 NR 37 TC 84 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2004 VL 58 IS 3 BP 927 EP 931 DI 10.1016/j.ijrobp.2003.09.092 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 773QP UT WOS:000188934600036 PM 14967452 ER PT J AU Foon, KA Yang, XD Weiner, LM Belldegrun, AS Figlin, RA Crawford, J Rowinsky, EK Dutcher, JP Vogelzang, NJ Gollub, J Thompson, JA Schwartz, G Bukowski, RM Roskos, LK Schwab, GM AF Foon, KA Yang, XD Weiner, LM Belldegrun, AS Figlin, RA Crawford, J Rowinsky, EK Dutcher, JP Vogelzang, NJ Gollub, J Thompson, JA Schwartz, G Bukowski, RM Roskos, LK Schwab, GM TI Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Symposium on Epidermal Growth Factor Receptor Inhibitors and Cancer Therapeutics CY JUN 04, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Radiat Therapy Oncol Grp, AstraZeneca Phamaceut, Bristrol-Meyers Squibb/Imclone Syst, Genentech, Novartis Oncol, Abgenix/Amgen, Wyeth Oncol DE ABX-EGF; epidermal growth factor; epidermal growth factor receptor; EGFR; transforming growth factor-alpha ID B-CELL DEVELOPMENT; MONOCLONAL-ANTIBODY; SIGNALING NETWORK; CHIMERIC ANTIBODY; CANCER-THERAPY; PHASE-I; MICE; EXPRESSION; KINASE; COMBINATION AB The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an extracellular ligand-binding domain and intracellular tyrosine kinase domain. Ligand binding induces EGFR dimerization and autophosphorylation on several tyrosine residues in the intracellular domain, leading to mitogenic signal transduction. EGFR overexpression correlates with a poor prognosis and is often associated with malignant transformation in a variety of epithelial cancers. ABX-EGF is a high-affinity (dissociation constant K-D = 5 X 10(-11) M) fully human IgG2 monoclonal antibody against human EGFR. ABX-EGF binds EGFR and blocks receptor binding of EGF and transforming growth factor-alpha, inhibiting EGFR tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor formation and eradicates large, established A431 tumors in xenograft models. Tumor growth inhibition occurs at relatively low doses, without concomitant chemotherapy or radiotherapy. When combined with chemotherapeutic agents, ABX-EGF has resulted in additive antitumor activity. A Phase I clinical trial has demonstrated activity in several tumor types, and the results from a Phase II trial for renal cell cancer also showed modest activity. Therapy was generally well tolerated without statistically significant adverse events. Monoclonal antibody blockade of EGFR represents a new and exciting direction in cancer therapy. (C) 2004 Elsevier Inc. C1 Abgenix Inc, Fremont, CA 94555 USA. Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Duke Univ, Med Ctr, Durham, NC USA. Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. Our Lady Mercy Canc Ctr, Dept Med, Bronx, NY USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Cleveland Clin, Taussig Canc Ctr, Ctr Drug Dev, Cleveland, OH 44106 USA. RP Yang, XD (reprint author), Abgenix Inc, 6701 Kaiser Dr, Fremont, CA 94555 USA. EM Xiao-Dong.Yang@abgenix.com NR 40 TC 159 Z9 168 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2004 VL 58 IS 3 BP 984 EP 990 DI 10.1016/j.ijrobp.2003.09.098 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 773QP UT WOS:000188934600044 PM 14967460 ER PT J AU Eribe, ERK Paster, BJ Caugant, DA Dewhirst, FE Stromberg, VK Lacy, GH Olsen, I AF Eribe, ERK Paster, BJ Caugant, DA Dewhirst, FE Stromberg, VK Lacy, GH Olsen, I TI Genetic diversity of Leptotrichia and description of Leptotrichia goodfellowii sp nov., Leptotrichia hofstadii sp nov., Leptotrichia shahii sp nov and Leptotrichia wadei sp nov. SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID BUCCALIS BACTEREMIA; BACTERIAL SYSTEMATICS; BACTEROIDES-FRAGILIS; TAXONOMY; PATIENT; ENDOCARDITIS; DATABASE; GENERA; ACIDS; RNA AB Sixty strains of Gram-negative, anaerobic, rod-shaped bacteria from human sources initially assigned to Leptotrichia buccalis (n = 58) and 'Leptotrichia pseudobuccalis' (n = 2) have been subjected to polyphasic taxonomy. Full-length 16S rDNA sequencing, DNA-DNA hybridization, RAPID, SDS-PAGE of whole-cell proteins, cellular fatty acid analysis and enzymic/biochemical tests supported the establishment of four novel Leptotrichia species from this collection, Leptotrichia goodfellowii sp. nov. (type strain LB 57(T) = CCUG 32286(T) = CIP 107915(T)), Leptotrichia hofstadii sp. nov. (type strain LB 23(T) = CCUG 47504(T) = CIP 107917(T)), Leptotrichia shahii sp. nov. (type strain LB 37(T) = CCUG 47503(T) = CIP = 107916(T)) and Leptotrichia wadei sp. nov. (type strain LB 16T = CCUG 47505(T) = CIP 107918(T)). Light and electron microscopy showed that the four novel species were Gram-negative, non-spore-forming and non-motile rods. L. goodfellowii produced arginine dihydrolase, beta-galactosidase, N-acetyl-beta-glucosaminidase, arginine arylamidase, leucine arylamidase and histidine arylamidase. L. shahii produced alpha-arabinosidase. L. buccalis and L. goodfellowii fermented mannose and were beta-galactosidase-6-phosphate positive. L. goodfellowii, L. hofstadii and L. wadei were beta-haemolytic. L. buccalis fermented raffinose. With L. buccalis, L. goodfellowii showed 3.8-5.5% DNA-DNA relatedness, L. shahii showed 24.5-34.1% relatedness, L. hofstadii showed 27.3-36.3% relatedness and L. wadei showed 24.1-35.9% relatedness. 16S rDNA sequencing demonstrated that L. hofstadii, L. shahii, L. wadei and L. goodfellowii each formed individual clusters with 97, 96, 94 and 92% similarity, respectively, to L. buccalis. C1 Univ Oslo, Fac Dent, Inst Oral Biol, N-0316 Oslo, Norway. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Norwegian Inst Publ Hlth, Div Infect Dis Control, N-0403 Oslo, Norway. Virginia Polytech Inst & State Univ, Dept Plant Pathol Physiol & Weed Sci, Blacksburg, VA 24061 USA. RP Eribe, ERK (reprint author), Univ Oslo, Fac Dent, Inst Oral Biol, POB 1052, N-0316 Oslo, Norway. EM emenike@odont.uio.no FU NIDCR NIH HHS [DE11443] NR 42 TC 32 Z9 35 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAR PY 2004 VL 54 BP 583 EP 592 DI 10.1099/ijs.0.02819-0 PN 2 PG 10 WC Microbiology SC Microbiology GA 807DA UT WOS:000220481000042 PM 15023979 ER PT J AU Trueba, G Zapata, S Madrid, K Cullen, P Haake, D AF Trueba, G Zapata, S Madrid, K Cullen, P Haake, D TI Cell aggregation: a mechanism of pathogenic Leptospira to survive in fresh water SO INTERNATIONAL MICROBIOLOGY LA English DT Article DE Leptospira; starvation; fresh-water survival; cellular aggregation; aqueous habitats ID OUTER-MEMBRANE PROTEIN; VISCOUS ENVIRONMENTS; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; LIPOPROTEIN; EPIDEMIC; GROWTH AB Transmission of leptospirosis is facilitated by the survival of pathogenic leptospires in moist environments outside their mammalian host. In the present study, the survival mechanisms of Leptospira interrogans serovar Canicola in aqueous conditions and lack of nutrients were investigated. In distilled water, leptospires were able to remain motile for 110 days (pH 7.2). However, when incubated in a semi-solid medium composed of distilled water and 0.5% purified agarose (pH 7.2), they survived 347 days. In this viscous environment, aggregates of live spirochetes were observed. Neither antibiotics (e.g. tetracycline and ampicillin) nor nutrients inhibited leptospiral aggregation. Immunoblot analysis suggested that cells incubated in water down-regulate the expression of LipL31, an inner-membrane protein, but retain expression of other membrane proteins. These studies provide insights into the mechanisms by which pathogenic Leptospira survives for prolonged periods of time in natural aqueous environments, a key stage in the leptospiral lifecycle. C1 Univ San Francisco Quito, Inst Microbiol, Quito, Ecuador. Monash Univ, Bacterial Pathogenesis Res Grp, Clayton, Vic 3800, Australia. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. RP Trueba, G (reprint author), Univ San Francisco Quito, Inst Microbiol, Via Interocean, Quito, Ecuador. EM gabriel@mail.usfq.edu.cc OI Trueba, Gabriel/0000-0003-2617-9021 FU NIAID NIH HHS [AI-34431] NR 28 TC 62 Z9 66 U1 1 U2 10 PU SPRINGER-VERLAG HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1139-6709 J9 INT MICROBIOL JI Int. Microbiol. PD MAR PY 2004 VL 7 IS 1 BP 35 EP 40 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 823IP UT WOS:000221604600006 PM 15179605 ER PT J AU Dana, MR AF Dana, MR TI Corneal antigen-presenting cells: Diversity, plasticity, and disguise - The Cogan lecture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; ENDOTHELIAL GROWTH-FACTOR; CHEMOKINE GENE-EXPRESSION; DRAINING LYMPH-NODES; DENDRITIC CELLS; LANGERHANS CELLS; ADHESION MOLECULES; VEGF-C; TRANSPLANT REJECTION; IMMUNE PRIVILEGE C1 Harvard Univ, Sch Med, Immunol Lab, Schepens Eye Res Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Immunol Lab, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02115 USA. EM dana@vision.eri.harvard.edu NR 74 TC 31 Z9 32 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 722 EP 727 DI 10.1167/iovs.03-0803 PG 6 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200002 PM 14985280 ER PT J AU Tsilimbaris, M Lit, ES Christoforidis, JB D'Amico, DJ AF Tsilimbaris, M Lit, ES Christoforidis, JB D'Amico, DJ TI In vivo rabbit eyecup preparation for use in retinal research SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VITRECTOMY AB PURPOSE. To develop an in vivo rabbit eyecup preparation that preserves neuronal and vascular connections with normal posterior segment contour, permitting direct access to the retina and facilitating retinal microsurgical and neuroscience research. METHODS. Cyanoacrylate glue was applied to the anterior sclera of six Dutch-belted rabbits before open-sky vitrectomy. The glue was used to harden the compliant scleral wall and to fix it to the surrounding periorbital tissues. RESULTS. A normal contour of the posterior segment was retained in all cases. Vitrectomy under air was successfully accomplished and an extensive removal of the vitreous gel was achieved. Fluorescein angiography revealed normal vascular patency of the retinal vessels after vitrectomy. CONCLUSIONS. The proposed modification of the rabbit eyecup retains the normal neurovascular connections and configuration of the retina, making it suitable for retinal microsurgical maneuvers or any procedures in which easy access to anatomically undisturbed retina is required. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02115 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02115 USA. EM djdamico@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 906 EP 909 DI 10.1167/iovs.03-0414 PG 4 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200033 PM 14985309 ER PT J AU Lyons, TJ Jenkins, AJ Zheng, DY Lackland, DT McGee, D Garvey, WT Klein, RL AF Lyons, TJ Jenkins, AJ Zheng, DY Lackland, DT McGee, D Garvey, WT Klein, RL CA DCCT EDIC Res Grp TI Diabetic retinopathy and serum lipoprotein subclasses in the DCCT/EDIC cohort SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; ENDOTHELIAL-CELLS; PITTSBURGH EPIDEMIOLOGY; COMPLICATIONS TRIAL; RISK-FACTORS; IDDM; LDL; NEPHROPATHY; ASSOCIATION AB PURPOSE. To determine associations between retinopathy status and detailed serum lipoprotein subclass profiles in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) cohort. METHODS. Persons with type 1 diabetes (440 women, 548 men) from the DCCT/EDIC cohort were studied. Retinopathy was characterized by Early Treatment Diabetic Retinopathy Study (ETDRS) scores, hard exudate scores, and ETDRS scores minus the hard exudate component. Lipoproteins were characterized by conventional lipid profile, nuclear magnetic resonance lipoprotein subclass profile (NMR-LSP), apoA1, apoB, lipoprotein(a), and susceptibility of LDL to oxidation. Data were analyzed with and without the following covariates: age, gender, duration of diabetes, HbA(1C), albumin excretion rate (AER), creatinine clearance, hypertension, body mass index, waist-hip ratio, DCCT treatment group, smoking status. RESULTS. The severity of retinopathy was positively associated with triglycerides (combined cohort) and negatively associated with HDL cholesterol (men, combined cohort). NMR-LSP iden-tified retinopathy as being positively associated with small and medium VLDL and negatively with VLDL size. In men only, retinopathy was positively associated with small LDL, LDL particle concentration, apoB concentration, and small HDL and was negatively associated with large LDL, LDL size, large HDL, and HDL size. No associations were found with apoA1, Lp(a), or susceptibility of LDL to oxidation. All three measures of retinopathy revealed the same associations. CONCLUSIONS. NMR-LSP reveals new associations between serum lipoproteins and severity of retinopathy in type 1 diabetes. The data are consistent with a role for dyslipoproteinemia involving lipoprotein subclasses in the pathogenesis of diabetic retinopathy. C1 Univ Oklahoma, Hlth Sci Ctr, Endocrinol Sect, Oklahoma City, OK 73104 USA. Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry, Charleston, SC 29425 USA. Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Lyons, TJ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Endocrinol Sect, 941 Stanton I Young Blvd,BSEB329A, Oklahoma City, OK 73104 USA. EM timothy-lyons@ouhsc.edu FU NHLBI NIH HHS [P01 HL55782] NR 42 TC 152 Z9 159 U1 1 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 910 EP 918 DI 10.1167/iovs.02-0648 PG 9 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200034 PM 14985310 ER PT J AU Jones, D AF Jones, D TI Pox Americana: The great smallpox epidemic of 1775-82 SO ISIS LA English DT Book Review RP Jones, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0021-1753 J9 ISIS JI Isis PD MAR PY 2004 VL 95 IS 1 BP 122 EP 123 DI 10.1086/423544 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA 832FT UT WOS:000222253400034 ER PT J AU Korthuis, PT Asch, SM Anaya, HD Morgenstern, H Goetz, MB Yano, EM Rubenstein, LV Lee, ML Bozzette, SA AF Korthuis, PT Asch, SM Anaya, HD Morgenstern, H Goetz, MB Yano, EM Rubenstein, LV Lee, ML Bozzette, SA TI Lipid screening in HIV-infected veterans SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; AIDS; hyperlipidemia; protease inhibitors; quality of health care ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITORS; ANTIRETROVIRAL THERAPY; UNITED-STATES; INSULIN-RESISTANCE; CARE; DISEASE; HYPERLIPIDEMIA; RISK; RECOMMENDATIONS AB Background: Lipid screening is recommended for patients taking protease inhibitors (PIs). Methods: We examined data from the Veterans Administration Immunology Case Registry to assess lipid screening among HIV-infected veterans who received Pis for at least 6 consecutive months during 1999 and 2001. We estimated crude and adjusted associations between lipid screening and patient characteristics (age, gender, HIV exposure, and race/ethnicity), comorbidities (AIDS, cardiovascular disease, diabetes, hypertension, smoking, and hyperlipidemia), and facility characteristics (urban location, case management, guidelines, and quality improvement programs) Results: Among 4065 patients on Pis, clinicians screened 2395 (59%) for lipids within 6 months of initiating treatment. Adjusting for patient characteristics, comorbidities, facility traits, and clustering, lipid screening was more common among patients who were cared for in urban areas (relative risk [RR] = 1.3, confidence limits: 1.0-1.5), diabetic (RR = 1,2, confidence limits: 1.1-1.3), or previously hyperlipidemic (RR = 1.4, confidence limits: 1.3-1.5) and less common among patients with a history of intravenous drug use (IVDU) (RR = 0.90, confidence limits: 0.79-1.0) or unknown HIV risk (RR = 0.85, confidence limits: 0.75-0.95). Conclusions: Six in 10 patients taking Pis receive lipid screening within 6 months of PI use. Systemic interventions to improve overall HIV quality of care should also address lipid screening, particularly among patients with unknown or IVDU HIV risk and those cared for in nonurban areas. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA HSR&D, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. San Diego VA Med Ctr, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu OI Goetz, Matthew/0000-0003-4542-992X NR 42 TC 10 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2004 VL 35 IS 3 BP 253 EP 260 DI 10.1097/00126334-200403010-00005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804WA UT WOS:000220327600005 PM 15076239 ER PT J AU Simmons, JH Thase, M Fava, M Hollander, S Igvy-May, N Boyle, KR Gibertini, M AF Simmons, JH Thase, M Fava, M Hollander, S Igvy-May, N Boyle, KR Gibertini, M TI Analysis of gepirone-ER on the Bech-6 and individual Hamd-17 item scores SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Meeting Abstract DE depression; antidepressants; psychopharmacology C1 Western Psychiat Inst & Clin, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Organon Pharmaceut USA Inc, Roseland, NJ 07068 USA. Organon Pharmaceut USA Inc, Global Med Serv, Roseland, NJ 07068 USA. EM john.simmons@organon.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2004 VL 78 SU 1 BP S129 EP S129 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 808UN UT WOS:000220594100159 ER PT J AU Duty, SM Calafat, AM Silva, MJ Brock, JW Ryan, L Chen, ZY Overstreet, J Hauser, R AF Duty, SM Calafat, AM Silva, MJ Brock, JW Ryan, L Chen, ZY Overstreet, J Hauser, R TI The relationship between environmental exposure to phthalates and computer-aided sperm analysis motion parameters SO JOURNAL OF ANDROLOGY LA English DT Article DE environment; epidemiology; human phthalate ID ASSISTED SEMEN ANALYSIS; QUANTITATIVE DETECTION; ALPHA-CHLOROHYDRIN; HUMAN SPERMATOZOA; PREDICTIVE VALUE; ADULT-RATS; QUALITY; MEN; METABOLITES; FERTILITY AB The general population is exposed to phthalates through consumer products, diet, and medical devices. The present study explored whether phthalates, reproductive toxins in laboratory animals, were associated with altered sperm movement characteristics in men. Two-hundred twenty subjects provided a semen sample for computer-aided sperm analysis (CASA) and a urine sample for measurement of phthalate monoesters, monoethyl (MEP), monobenzyl (MBzP), mono-n-butyl (MBIP), mono-2-ethylhexyl (MEHP), and monomethyl (MMP). Three CASA parameters, straight-line velocity (VSL), curvilinear velocity (VCL), and linearity (LIN), were used as measures of sperm progression, sperm vigor, and swimming pattern, respectively. There were suggestive dose-response relationships (shown as the predicted change in mean sperm motion parameter for the second and third tertiles compared with the first tertile; P value for trend) for MBzP with VSL (-2.36 mum/s, -2.81 mum/s; P = .09) and VCL (-1.67 mum/s, -2.45 mum/s; P =.4). There were suggestive negative associations between MBP and VSL (-3.07 mum/s, -2.87 mum/ s; P = .08) and VCL (-3.25 mum/s; -3.46 mum/s; P = .2), and between MEHP with VSL (-1.09 mum/s, -2.73 mum/s; P = .1) and VCL (-0.29 mum/s, -2.93 mum/s; P = .3). In contrast to the other phthalates, MEP was positively associated with VSL and VCL but negatively associated with LIN. No consistent relationship was found for MMP and any sperm motion parameter. Although we did not find statistically significant associations, trends between CASA parameters, sperm velocity, and forward progression, and increased urinary levels of MBP, MBzP, and MEHP warrant further follow-up. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Simmons Coll, Sch Hlth Studies, Nursing Programs, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Univ Calif Davis, Sch Med, Dept Obstet & Gynecol, Div Reprod Biol & Med, Davis, CA 95616 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [T32 ES07069, ES09718, ES00002] NR 47 TC 78 Z9 82 U1 4 U2 10 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2004 VL 25 IS 2 BP 293 EP 302 PG 10 WC Andrology SC Endocrinology & Metabolism GA 780LM UT WOS:000189382200020 PM 14760016 ER PT J AU Beaulieu, V Pastor-Soler, N Da Silva, N Brown, C Smith, P Kwiatkowski, D Brown, D Breton, S AF Beaulieu, V Pastor-Soler, N Da Silva, N Brown, C Smith, P Kwiatkowski, D Brown, D Breton, S TI Role of gelsolin and calcium in the regulation of pH-dependent V-ATPase recycling in the epididymis SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-of-Andrology (ASA 2004) CY APR 17-20, 2004 CL Baltimore, MD SP Amer Soc Androl C1 Massachusetts Gen Hosp, PMB, Charlestown, MA 02129 USA. Biocurrents Res Ctr, Woods Hole, MA 02543 USA. BWH, Div Hematol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2004 SU S MA 114 BP 76 EP 76 PG 1 WC Andrology SC Endocrinology & Metabolism GA 803LE UT WOS:000220231800115 ER PT J AU Da Silva, N Beaulieu, V Breton, S AF Da Silva, N Beaulieu, V Breton, S TI Postnatal expression of aquaporin 9 mRNA in rat epididymal epithelial cells by LCM and real-time PCR SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-of-Andrology (ASA 2004) CY APR 17-20, 2004 CL Baltimore, MD SP Amer Soc Androl C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Prog Membr Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2004 SU S MA 115 BP 76 EP 76 PG 1 WC Andrology SC Endocrinology & Metabolism GA 803LE UT WOS:000220231800116 ER PT J AU Pietrement, C Da Silva, N Sun-Wada, GH Marshansky, V Brown, D Futai, M Breton, S AF Pietrement, C Da Silva, N Sun-Wada, GH Marshansky, V Brown, D Futai, M Breton, S TI Specific distribution of the V-ATPase subunit isoforms in rat epididymis and VAS deferens SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-of-Andrology (ASA 2004) CY APR 17-20, 2004 CL Baltimore, MD SP Amer Soc Androl C1 Massachusetts Gen Hosp, Prog Membr Biol, Charlestown, MA USA. Osaka Univ, Div Biol Sci, ISIR, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2004 SU S MA 113 BP 76 EP 76 PG 1 WC Andrology SC Endocrinology & Metabolism GA 803LE UT WOS:000220231800114 ER PT J AU Apostolou, I von Boehmer, H AF Apostolou, I von Boehmer, H TI The TCR-HA, INS-HA transgenic model of autoimmune diabetes: limitations and expectations SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID REGULATORY T-CELLS; GENE-EXPRESSION; SELF-PEPTIDE; BETA-CELLS; ANTIGEN; MICE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. EM harald-von-boehmer@dfci.harvard.edu NR 15 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD MAR PY 2004 VL 22 IS 2 BP 111 EP 114 DI 10.1016/j.jaut.2003.10.005 PG 4 WC Immunology SC Immunology GA 803JJ UT WOS:000220227100003 PM 14987738 ER PT J AU Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF AF Pierce, MC Strasswimmer, J Park, BH Cense, B de Boer, JF TI Birefringence measurements in human skin using polarization-sensitive optical coherence tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical imaging; polarization; Stokes parameters; dermatology; collagen; wound healing ID RESOLVED MUELLER MATRIX; BIOLOGICAL TISSUE; FIBER; INTERFEROMETER AB Optical coherence tomography enables cross-sectional imaging of tissue structure to depths of around 1.5 mm, at high-resolution and in real time. Incorporation of polarization sensitivity (PS) provides an additional contrast mechanism which is complementary to images mapping backscattered intensity only. We present here polarization-sensitive optical coherence tomography (OCT) images of human skin in vivo, demonstrating the ability of the technique to visualize and quantify the birefringent properties of skin. Variation in normal skin birefringence according to anatomical location is demonstrated, and discussed in relation to collagen distribution at each location. From measurements on a sample of five human volunteers, mean double-pass phase retardation rates of 0.340 +/- 0.143, 0.250 +/- 0.076, and 0.592 +/- 0.142 deg/mum were obtained for the dorsal hand, temple, and lower back regions, respectively. We demonstrate how averaging the Stokes parameters of backscattered light over a range of axial and lateral dimensions results in a reduction of speckle-induced noise. Examples of PS-OCT images from skin sites following wound healing and repair are also presented and discussed. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA. EM pierce@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; strasswimmer, john/0000-0002-5790-2633 NR 32 TC 93 Z9 95 U1 1 U2 11 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2004 VL 9 IS 2 BP 287 EP 291 DI 10.1117/1.16457971 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 810KC UT WOS:000220702200008 PM 15065893 ER PT J AU Strasswimmer, J Pierce, MC Park, BH Neel, V de Boer, JF AF Strasswimmer, J Pierce, MC Park, BH Neel, V de Boer, JF TI Polarization-sensitive optical coherence tomography of invasive basal cell carcinoma SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE basal cell carcinoma; optical coherence tomography; birefringence; collagen ID REAL-TIME; DIAGNOSIS; SKIN; FLOW AB Skin cancer is the most common human malignancy, with basal cell carcinoma (BCC) the most frequent type. Aggressive forms of BCC are associated with extensive dermal invasion and destruction of collagen. Surgery is the most common treatment, but identification of tumor borders is a challenge. Polarization-sensitive optical coherence tomography (PS-OCT) is an optical method to examine collagen birefringence. To date, it has not been exploited for cancer management. As part of a pilot exploratory study to examine the use of OCT in skin cancer, we examined several tumors that pose a challenge to the surgeon due to their large size and histological subtype. In normal perilesional skin, OCT identifies epidermal and dermal structure; PS-OCT identified dermal birefringence. In BCC, tumors lost normal structure and gained the appearance of lobular impressions. PS-OCT identified an alteration of dermal birefringence. Examination of a border area revealed a gradual transition from more normal appearing image to frank tumor. These results indicate that PS-OCT can identify features that distinguish normal skin from tumor and may have the potential to guide surgeons in the treatment of aggressive skin cancer. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Strasswimmer, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, 50 Blossom St, Boston, MA 02114 USA. EM jstrasswimmer@PARTNERS.ORG; jdeboer@PARTNERS.ORG RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; strasswimmer, john/0000-0002-5790-2633 FU PHS HHS [T32] NR 17 TC 94 Z9 94 U1 1 U2 12 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2004 VL 9 IS 2 BP 292 EP 298 DI 10.1117/1.16441181 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 810KC UT WOS:000220702200009 PM 15065894 ER PT J AU Rajadhyaksha, M AF Rajadhyaksha, M TI Detectability of contrast agents for confocal reflectance imaging of skin and microcirculation SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE confocal; microscopy; detectability; contrast agents; imaging; skin; microcirculation ID SCANNING LASER MICROSCOPY; LIGHT-SCATTERING; IN-VIVO; REFRACTIVE-INDEX; BACKGROUND REJECTION; BIOLOGICAL CELLS; POLARIZED-LIGHT; TISSUE; SIZE; SPECTROSCOPY AB Confocal reflectance microscopy of skin and other tissues in vivo is currently limited to imaging at the cellular, nuclear and general architectural levels due to the lack of microstructure-specific contrast. Morphologic and functional imaging at specific organelle and microstructure levels may require the use of exogenous contrast agents in small (nontoxic) concentrations, from which weakly backscattered light must be detected in real time. We report an analysis based on Mie theory to predict detectability, in terms of signal-to-background and signal-to-noise ratios, of reflectance contrast agents within skin and microcirculation. The analysis was experimentally verified by detectability of (a) intravenously injected polystyrene microspheres that enhance the contrast of dermal microcirculation in Sprague-Dawley rats, and (b) acetic acid-induced compaction of chromatin that enhances nuclear morphology in normal and cancerous human skin. Such analyses and experiments provide a quantitative basis for developing the opto-biochemical properties and use of contrast agents and for designing confocal instrumentation to enable real-time detectability in vivo. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Northeastern Univ, Ctr Subsurface Sensing & Imaging Syst, Stearns Ctr 302, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Serv Dermatol, New York, NY 10022 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Rochester, Inst Opt, Rochester, NY 14627 USA. RP Rajadhyaksha, M (reprint author), Northeastern Univ, Ctr Subsurface Sensing & Imaging Syst, Stearns Ctr 302, Boston, MA 02115 USA. EM rajadmil@ece.neu.edu NR 45 TC 27 Z9 30 U1 0 U2 4 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2004 VL 9 IS 2 BP 323 EP 331 DI 10.1117/1.1646175 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 810KC UT WOS:000220702200013 PM 15065898 ER PT J AU Roegener, A Brinkmann, R Lin, CP AF Roegener, A Brinkmann, R Lin, CP TI Pump-probe detection of laser-induced microbubble formation in retinal pigment epithelium cells SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE RPE; retinal pigment epithelium; melanosome; pump-probe; cavitation; microbubble ID PHOTOCOAGULATION; MICROCAVITATION; RADIATION AB Microsecond laser pulses are currently being investigated in a new ophthalmic procedure for treatment of disorders associated with the retinal pigment epithelium (RPE). The precise mechanism for microsecond laser-induced RPE damage, however, has not been determined. We have previously shown that short pulse laser irradiation in the nanosecond to picosecond time domain causes transient microbubble formation around melanin granules in pigmented cells. Nanosecond time-resolved microscopy was previously used to visualize the intracellular cavitation dynamics. However, this technique is difficult to use with microsecond laser exposures, especially when multiple laser pulses are applied in a rapid sequence as in the clinical setting. Here we describe a simple pump-probe method for detecting transient light scattering signal from individual RPE cells when they. are irradiated with nanosecond and microsecond laser pulses. For single 12 ns pulses the threshold for bubble detection was the same as the ED50 threshold for cell death. For 6 mus pulse duration the threshold for bubble detection was about 10% higher than the threshold for cell death. With repetitive pulse trains at 500 Hz the ED50 decreased about 25% for 10 and 100 pulses. Cells die when a single bubble was detected in a multiple pulse sequence. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Bielefeld, D-33615 Bielefeld, Germany. Med Laser Ctr Luebeck, Lubeck, Germany. RP Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, BHX 630, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu RI Brinkmann, Ralf/E-6701-2012 FU NEI NIH HHS [R01 EY 12970] NR 14 TC 28 Z9 29 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2004 VL 9 IS 2 BP 367 EP 371 DI 10.1117/1.16464131 PG 5 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 810KC UT WOS:000220702200019 PM 15065904 ER PT J AU Quaresima, V Ferrari, M Franceschini, MA Hoimes, ML Fantini, S AF Quaresima, V Ferrari, M Franceschini, MA Hoimes, ML Fantini, S TI Spatial distribution of vastus lateralis blood flow and oxyhemoglobin saturation measured at the end of isometric quadriceps contraction by multichannel near-infrared spectroscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near-infrared; muscle; exercise; frequency-domain; muscle oxygen saturation ID PERIPHERAL VASCULAR-DISEASE; SKELETAL-MUSCLE; OXYGEN-CONSUMPTION; CALF MUSCLE; DYNAMIC EXERCISE; O-2 CONSUMPTION; ADIPOSE-TISSUE; PIGLET BRAIN; HUMANS; HEMOGLOBIN AB Muscle blood flow (MBF) and muscle oxygen saturation (SmO2) were measured at eight locations, (four proximal, four distal) over a 4 X 8 cm(2) area of the vastus lateralis at rest and immediately after isometric, maximal quadriceps contraction using multichannel, frequency-domain, near-infrared spectroscopy. A venous occlusion was applied 20 s before the end of the exercise, so that the venous-occlusion-induced increase in total hemoglobin was recorded without any delay after the end of the exercise. Therefore, we were able to investigate the relationship between the exercise-induced changes in vastus lateralis MBF and SmO2. After exercise, MBF increased significantly at each measured location. Comparing the MBF values measured at the end of exercise in the proximal and distal regions, we observed that only one proximal region had a significantly higher MBF than the corresponding distal one. The maximum desaturation measured during exercise was positively correlated with the postexercise to pre-exercise MBF ratio in both the proximal (P= 0.016) and distal (P= 0.0065) regions. These data confirm that frequency-domain tissue oximeters are noninvasive, powerful tools to investigate the spatial and temporal features of muscle blood flow and oxygenation, with potential applications in areas of pathophysiology. (C) 2004 Society of Photo-Optical Instrumentation Engineers. C1 Univ Aquila, Dept Biomed Sci & Technol, I-67100 Laquila, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. Tufts Univ, Ctr Bioengn, Dept Biomed Engn, Medford, MA 02155 USA. RP Quaresima, V (reprint author), Univ Aquila, Dept Biomed Sci & Technol, I-67100 Laquila, Italy. EM vale@univaq.it OI FERRARI, Marco/0000-0002-3041-2917; quaresima, valentina/0000-0001-9884-0304 FU NIBIB NIH HHS [R01 EB001954-04A2, R01 EB001954, R01 EB001954-05]; NICHD NIH HHS [R01-HD42908]; NIMH NIH HHS [R01-MH62854] NR 37 TC 23 Z9 23 U1 0 U2 1 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAR-APR PY 2004 VL 9 IS 2 BP 413 EP 420 DI 10.1117/1.1646417 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 810KC UT WOS:000220702200025 PM 15065910 ER PT J AU Jain, N Pietrobon, R Hocker, S Guller, U Shankar, A Higgins, LD AF Jain, N Pietrobon, R Hocker, S Guller, U Shankar, A Higgins, LD TI The relationship between surgeon and hospital volume and outcomes for shoulder arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL JOINT ARTHROPLASTY; TOTAL HIP; MULTIPLE IMPUTATION; KNEE REPLACEMENT; RETRANSFORMATION PROBLEM; CORONARY ANGIOPLASTY; PATIENT OUTCOMES; SURGICAL VOLUME; MISSING DATA; MORTALITY AB Background: As far as we know, no previous study has determined the relationship between volume and outcomes for shoulder arthroplasty. We hypothesized that surgeons and hospitals with higher caseloads of total shoulder arthroplasties and hemiarthroplasties have better outcomes as measured by decreased mortality rate, shorter length of stay in the hospital, reduced postoperative complications, and routine disposition of patients on discharge. Methods: Data on patients undergoing shoulder arthroplasty were extracted from the Nationwide Inpatient Sample data-bases for the years 1988 through 2000. Logistic regression with generalized estimating equations and multiple linear regression models were used to estimate the adjusted association between surgeon and hospital volume and outcomes for total shoulder arthroplasty and hemiarthroplasty after adjusting for comorbidity, age, race, household income, and sex. Results: The mortality rates for patients who had a total shoulder arthroplasty performed by surgeons who did fewer than two procedures per year (0.36%) or who did between two and fewer than four procedures per year (0.32%) were higher than those for patients who had a total shoulder arthroplasty performed by surgeons who did four procedures or more per year (0.20%). The risk-adjusted rate of postoperative complications after hemiarthroplasty was significantly higher for patients managed by surgeons who performed fewer than two procedures per year (1.68%) than for those managed by surgeons with a volume of five procedures or more per year (0.97%). The possibility of postoperative complications when total shoulder arthroplasty was performed in hospitals with a volume of fewer than five procedures (1.44%) or in those with a volume of five to ten procedures per year (1.45%) was significantly higher than that in hospitals where ten procedures or more were performed every year (0.64%). The mean lengths of stay in the hospital after total shoulder arthroplasty and hemiarthroplasty were significantly longer when the operations were performed by surgeons who did fewer than two procedures per year or when they were done in hospitals with a volume of fewer than five procedures per year or with a volume of five to fewer than ten procedures per year than when they were done in hospitals or by surgeons in the highest volume category (p < 0.001). Conclusions: Patients who have a total shoulder arthroplasty or hemiarthroplasty performed by a high-volume surgeon or in a high-volume hospital are more likely to have a better outcome. Level of Evidence: Therapeutic study, Level III-2 (retrospective cohort study). See Instructions to Authors for a complete description of levels of evidence. C1 Duke Univ, Med Ctr, Ctr Excellence Surg Outcomes, Durham, NC USA. Duke Univ, Med Ctr, Div Orthopaed Surg, Durham, NC USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI USA. Univ Basel, Dept Gen Surg, Basel, Switzerland. RP Jain, N (reprint author), Va Boston Healthcare Syst, 1400 VFW Parkway,Pulm IIIB, W Roxbury, MA 02132 USA. EM nitin_jain@hms.harvard.edu NR 55 TC 108 Z9 108 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2004 VL 86A IS 3 BP 496 EP 505 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 779AF UT WOS:000189272900006 PM 14996874 ER PT J AU Liu, GS Jupiter, JB AF Liu, GS Jupiter, JB TI Posterolateral rotatory elbow subluxation with intra-articular entrapment of the radial nerve - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TRAUMATIC POSTERIOR DISLOCATION; MEDIAN-NERVE; INTEROSSEOUS NERVE; HEAD; CHILDREN; INSTABILITY; FRACTURES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Liu, GS (reprint author), Massachusetts Gen Hosp, 15 Parkman St,GRB 6, Boston, MA 02114 USA. EM jjupiter1@partners.org NR 30 TC 0 Z9 0 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2004 VL 86A IS 3 BP 603 EP 606 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 779AF UT WOS:000189272900023 PM 14996891 ER PT J AU White, MJ Zapka, JG Coghlin-Strom, J Alexander, MK Bauer-Wu, S AF White, MJ Zapka, JG Coghlin-Strom, J Alexander, MK Bauer-Wu, S TI Interdisciplinary collaboration for health professional education in cancer control SO JOURNAL OF CANCER EDUCATION LA English DT Article ID PUBLIC-HEALTH; COLORECTAL-CANCER; UNITED-STATES; MEDICINE; POPULATION; PROGRAM; RISK; MAMMOGRAPHY; PREVENTION; ETHNICITY AB Background. Overlapping responsibilities of health care delivery professionals in the United States has propelled medical, graduate nursing, and public health schools to rethink their curricula. The University of Massachusetts Medical School implemented the Cancer Prevention and Control Education (CPACE) initiative, an interdisciplinary curriculum focusing on behavioral and psychosocial aspects of cancer prevention, control, and research. Methods. An interdisciplinary Operations Committee developed courses, clerkships, and programs. Continuing education programs stressed the team approach. Results and Discussion. CPACE teaching objectives were congruent in the three schools, but logistical issues were challenging. Positive preevaluations and postevaluations indicated potential for shaping a collaborative attitude among health care providers. C1 Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Family & Community Med, Worcester, MA 01655 USA. Univ Massachusetts, Grad Sch Nursing, Worcester, MA 01655 USA. Dana Farber Canc Inst, Cantor Ctr Res Nursing & Patient Care, Boston, MA 02115 USA. RP Bauer-Wu, S (reprint author), Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM Maryjo.White@umassmed.edu FU NCI NIH HHS [R25CA71737] NR 56 TC 2 Z9 2 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2004 VL 19 IS 1 BP 37 EP 44 DI 10.1207/s15430154jce1901_10 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 814ZT UT WOS:000221013300009 PM 15059754 ER PT J AU Pitteloud, N Villegas, J Dwyer, AA Crowley, WF McPhaul, MJ Hayes, FJ AF Pitteloud, N Villegas, J Dwyer, AA Crowley, WF McPhaul, MJ Hayes, FJ TI Clinical case seminar - Acute stress masking the biochemical phenotype of partial androgen insensitivity syndrome in a patient with a novel mutation in the androgen receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PULSATILE LUTEINIZING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; REPRODUCTIVE FUNCTIONS; TESTOSTERONE LEVELS; INDUCED INHIBITION; CRITICAL ILLNESS; SECRETION; CORTISOL; GENE AB Hypogonadism has traditionally been classified as either hypogonadotropic or hypergonadotropic based on serum gonadotropin levels. However, when hypothalamic suppression of GnRH secretion occurs, it can mask an underlying hypergonadotropic state. In this report we document the unusual case of a 61-yr-old man with androgen insensitivity and coincidental functional hypogonadotropic hypogonadism (HH). Although functional HH is not a well-recognized entity in the male, major stress has been reported to cause transient suppression of the hypothalamic-pituitary-gonadal axis in men. The patient in question was noted to have undervirilization, minimal pubertal development, hypogonadal testosterone, and low gonadotropin levels consistent with congenital HH during a hospital admission for myocardial infarction. However, the patient had also had surgery for hypospadias, a clinical feature not typically part of the phenotypic spectrum of congenital HH. We therefore hypothesized that the combination of acute stress and chronic glucocorticoid administration for temporal arteritis induced transient HH in a patient with a disorder of sexual differentiation in whom gonadotropin levels would have otherwise been elevated. Using clinical, molecular, and genetic studies, the patient was found to have partial androgen insensitivity syndrome ( PAIS) caused by a novel mutation ( Ser(740)Cys) in the ligand-binding domain of the androgen receptor. Subsequent studies of the patient confirmed the characteristic gonadotropin and sex steroid abnormalities of PAIS. We describe for the first time a patient with PAIS presenting with a reversible hypogonadotropic biochemical profile triggered by an acute illness and corticosteroid therapy. This case highlights the necessity for caution when interpreting gonadotropin levels during acute stress. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NICHD NIH HHS [R01 HD015788, R01-HD-15788, U54 HD028138, U54 HD029164]; NIDDK NIH HHS [DK-03892] NR 36 TC 2 Z9 2 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2004 VL 89 IS 3 BP 1053 EP 1058 DI 10.1210/jc.2003-031373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 800LV UT WOS:000220030700004 PM 15001585 ER PT J AU Leder, BZ Rohrer, JL Rubin, SD Gallo, J Longcope, C AF Leder, BZ Rohrer, JL Rubin, SD Gallo, J Longcope, C TI Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; MIDDLE-AGED MEN; OLDER MEN; BODY-COMPOSITION; BIOAVAILABLE TESTOSTERONE; LUTEINIZING-HORMONE; REPLACEMENT THERAPY; HYPOGONADAL MEN; TRANSDERMAL TESTOSTERONE; SECONDARY HYPOGONADISM AB As men age, serum testosterone levels decrease, a factor that may contribute to some aspects of age-related physiological deterioration. Although androgen replacement has been shown to have beneficial effects in frankly hypogonadal men, its use in elderly men with borderline hypogonadism is controversial. Furthermore, current testosterone replacement methods have important limitations. We investigated the ability of the orally administered aromatase inhibitor, anastrozole, to increase endogenous testosterone production in 37 elderly men ( aged 62 - 74 yr) with screening serum testosterone levels less than 350 ng/dl. Subjects were randomized in a double-blind fashion to the following 12-wk oral regimens: group 1: anastrozole 1 mg daily (n = 12); group 2: anastrozole 1 mg twice weekly ( n = 11); and group 3: placebo daily ( n = 14). Hormone levels, quality of life (MOS Short-Form Health Survey), sexual function ( International Index of Erectile Function), benign prostate hyperplasia severity ( American Urological Association Symptom Index Score), prostate-specific antigen, and measures of safety were compared among groups. Mean +/- SD bioavailable testosterone increased from 99 +/- 31 to 207 +/- 65 ng/dl in group 1 and from 115 +/- 37 to 178 +/- 55 ng/dl in group 2 ( P < 0.001 vs. placebo for both groups and P = 0.054 group 1 vs. group 2). Total testosterone levels increased from 343 +/- 61 to 572 +/- 139 ng/dl in group 1 and from 397 +/- 106 to 520 +/- 91 ng/dl in group 2 ( P < 0.001 vs. placebo for both groups and P = 0.012 group 1 vs. group 2). Serum estradiol levels decreased from 26 +/- 8 to 17 +/- 6 pg/ml in group 1 and from 27 +/- 8 to 17 +/- 5 pg/ml in group 2 ( P < 0.001 vs. placebo for both groups and P = NS group 1 vs. group 2). Serum LH levels increased from 5.1 +/- 4.8 to 7.9 +/- 6.5 U/liter and from 4.1 +/- 1.6 to 7.2 +/- 2.8 U/liter in groups 1 and 2, respectively ( P = 0.007 group 1 vs. placebo, P = 0.003 group 2 vs. placebo, and P = NS group 1 vs. group 2). Scores for hematocrit, MOS Short-Form Health Survey, International Index of Erectile Function, and American Urological Association Symptom Index Score did not change. Serum prostate-specific antigen levels increased in group 2 only (1.7 +/- 1.0 to 2.2 +/- 1.5 ng/ml, P = 0.031, compared with placebo). These data demonstrate that aromatase inhibition increases serum bioavailable and total testosterone levels to the youthful normal range in older men with mild hypogonadism. Serum estradiol levels decrease modestly but remain within the normal male range. The physiological consequences of these changes remain to be determined. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Obstet & Gynecol, Worcester, MA 01655 USA. AstraZeneca Pharmaceut, Wilmington, DE 19850 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Bulfinch 327,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [K23-RR16310] NR 60 TC 82 Z9 88 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2004 VL 89 IS 3 BP 1174 EP 1180 DI 10.1210/jc.2003-031467 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 800LV UT WOS:000220030700024 PM 15001605 ER PT J AU Callahan, HS Cummings, DE Pepe, MS Breen, PA Matthys, CC Weigle, DS AF Callahan, HS Cummings, DE Pepe, MS Breen, PA Matthys, CC Weigle, DS TI Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GASTRIC BYPASS-SURGERY; PRADER-WILLI-SYNDROME; GROWTH-HORMONE SECRETAGOGUE; CIRCULATING GHRELIN; FOOD-INTAKE; WEIGHT-LOSS; ACYLATED PEPTIDE; BODY-WEIGHT; RATS; SECRETION AB Plasma ghrelin levels rise before meals and fall rapidly afterward. If ghrelin is a physiological meal-initiation signal, then a large oral caloric load should suppress ghrelin levels more than a small caloric load, and the request for a subsequent meal should be predicted by recovery of the plasma ghrelin level. To test this hypothesis, 10 volunteers were given, at three separate sessions, liquid meals ( preloads) with widely varied caloric content (7.5%, 16%, or 33% of total daily energy expenditure) but equivalent volume. Preloads were consumed at 0900 h, and blood was sampled every 20 min from 0800 h until 80 min after subjects spontaneously requested a meal. The mean ( +/- SE) intervals between ingestion of the 7.5%, 16%, and 33% preloads and the subsequent voluntary meal requests were 247 +/- 24, 286 +/- 20, and 321 +/- 27 min, respectively ( P = 0.015), and the nadir plasma ghrelin levels were 80.2 +/- 2.8%, 72.7 +/- 2.7%, and 60.8 +/- 2.7% of baseline ( the 0900 h value), respectively ( P < 0.001). A Cox regression analysis failed to show a relationship between ghrelin profile and the spontaneous meal request. We conclude that the depth of postprandial ghrelin suppression is proportional to ingested caloric load but that recovery of plasma ghrelin is not a critical determinant of intermeal interval. C1 Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Weigle, DS (reprint author), Univ Washington, Harborview Med Ctr, Box 359757,325 9th Ave, Seattle, WA 98104 USA. EM weigle@u.washington.edu FU NCRR NIH HHS [RR00037]; NIDDK NIH HHS [DK02860, DK17047, DK35816, DK55460, DK61516] NR 43 TC 166 Z9 170 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2004 VL 89 IS 3 BP 1319 EP 1324 DI 10.1210/jc.2003-031267 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 800LV UT WOS:000220030700047 PM 15001628 ER PT J AU Fan, VS Au, DH McDonell, MB Fihn, SD AF Fan, VS Au, DH McDonell, MB Fihn, SD TI Intraindividual change in SF-36 in ambulatory clinic primary care patients predicted mortality and hospitalizations SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE quality of life; hospitalization; mortality; cohort study; regression analysis; risk adjustment ID QUALITY-OF-LIFE; HEALTH-STATUS; VETERANS-AFFAIRS; DISEASE; RISK; OUTCOMES AB Objective: We sought to determine whether change in SF-36 scores over time is associated with the risk of adverse outcomes. dStudy Design and Setting: 7,702 participants in the Ambulatory Care Quality Improvement Project who completed a baseline and 1-year SF-36. Using logistic regression methods we estimated the 1-year risk of hospitalization and death based on previous 1-year changes in the physical (PCS) and mental (MCS) component summary scores. Results: After adjusting for baseline PCS scores, age, VA hospital site, distance to VA, and comorbidity, a >10-point decrease in PCS score was associated with an increased risk of death (OR 2.3, 95% CI 1.6-3.4) and hospitalization (OR 1.8, 1.4-2.2). An increased risk was also seen with a >10-point decrease in the MCS (OR for death, 1.6, 1.1-2.3; OR for hospitalization 1.5, 1.2-1.8). Conclusion: Change in SF-36 PCS and MCS scores is associated with mortality and hospitalizations, and provides important prognostic information over baseline scores alone. (C) 2004 Elsevier Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Ctr Excellence, Hlth Serv Res & Dev 152, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Fan, VS (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence, Hlth Serv Res & Dev 152, 1600 S Columbian Way, Seattle, WA 98108 USA. EM vfan@u.washington.edu NR 31 TC 21 Z9 21 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAR PY 2004 VL 57 IS 3 BP 277 EP 283 DI 10.1016/j.jclinepi.2003.08.004 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 814OH UT WOS:000220983500008 PM 15066688 ER PT J AU Sloan, KL Straits-Troster, KA Dominitz, JA Kivlahan, DR AF Sloan, KL Straits-Troster, KA Dominitz, JA Kivlahan, DR TI Hepatitis C tested prevalence and comorbidities among veterans in the US Northwest SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE hepatitis C; epidemiology; veterans; screening ID VIRUS-INFECTION; UNITED-STATES AB Goals: (1) Investigate the epidemiology of hepatitis C virus infection among patients seen in the Veterans Administration Northwest Network; (2) examine time trends in testing practices and results; and (3) estimate the prevalence of hepatitis C virus infection among active patients. Background: Hepatitis C virus infection causes chronic hepatitis and cirrhosis and is a leading cause of end-stage liver disease. Hepatitis C virus antibodies are estimated to be present in 1.8% of the US population, but reports of its prevalence among US veterans range from 1.7 to 35%. Study: Retrospective review of computerized medical records of veterans tested for hepatitis C from October 1994 through December 2000 (n = 37,938) at 8 Northwest Veterans Administration Medical Centers. Results: Among tested veterans, 8230 (21.7%) had evidence of hepatitis C virus infection. The number of patients tested increased annually from 2335 to 18,191, while the proportion with first-time positive hepatitis C test results decreased from 35 to 10%. This drop in tested prevalence was associated with a shift away from testing individuals at highest risk-those with positive hepatitis B serostatus, repeatedly elevated alanine transaminase levels, and drug use disorder diagnoses. We estimate that 11.4% of the Northwest Network veteran users are hepatitis C virus seropositive, with a lower bound of 4.0% and upper bound of 19.5%. Conclusions: Although estimates of hepatitis C virus infection rates among veteran users of the Veterans Administration system remain higher than those for the general population, changes in testing practice make generalizations from earlier studies hazardous. C1 Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. NW Hepatitis C Resource Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Vet Affairs Ctr Excellence Subst Abuse Treatment, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Gastroenterol Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Sloan, KL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mental Hlth Serv, 116-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. EM Kevin.Sloan@med.va.gov OI Dominitz, Jason/0000-0002-8070-7086 NR 10 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAR PY 2004 VL 38 IS 3 BP 279 EP 284 DI 10.1097/00004836-200403000-00016 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 776JR UT WOS:000189113300016 PM 15128077 ER PT J AU Deeks, SG Walker, BD AF Deeks, SG Walker, BD TI The immune response to AIDS virus infectivon: good, bad, or both? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID SOOTY MANGABEYS; HIV-INFECTION; ANTIRETROVIRAL THERAPY; LEVEL VIREMIA; T-CELLS; IMMUNODEFICIENCY; DISEASE; ACTIVATION; ADAPTATION; TURNOVER AB A potent antigen-specific T cell response to HIV infection can contribute to the control of viral replication and is therefore beneficial to the host. However, HIV-mediated increases in generalized T cell activation also appear to accelerate both viral replication and CD4+ T cell depletion. A new study in the JCI attempts to experimentally distinguish the beneficial versus harmful aspects of this immune response (see the related article beginning on page 836). C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Walker, BD (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. EM bwalker@partners.org NR 18 TC 55 Z9 58 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2004 VL 113 IS 6 BP 808 EP 810 DI 10.1172/JCI200421318 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 803ZO UT WOS:000220269200007 PM 15067312 ER PT J AU Quinones, MP Ahuja, SK Jimenez, F Schaefer, J Garavito, E Rao, A Chenaux, G Reddick, RL Kuziel, WA Ahuja, SS AF Quinones, MP Ahuja, SK Jimenez, F Schaefer, J Garavito, E Rao, A Chenaux, G Reddick, RL Kuziel, WA Ahuja, SS TI Experimental arthritis in CC chemokine receptor 2-null mice closely mimics severe human rheumatoid arthritis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; II COLLAGEN; T-CELLS; DBA/1 MICE; INFLAMMATORY ARTHRITIS; MONOCLONAL-ANTIBODIES; INFLAMED JOINTS; SYNOVIAL-FLUID; LYMPHOCYTES-T; MOUSE MODEL AB The prevailing paradigm is that in human rheumatoid arthritis (RA), the accumulation of monocytes and T cells in the joint, mediated in part by such CC chemokine receptors (CCRs) as CCR2 and CCR5, respectively, plays a central role in disease pathogenesis. To further validate this paradigm, we conducted proof-of-principle studies and tested the hypothesis that gene inactivation of Ccr2 or CcrS will ameliorate experimental RA. Contrary to our expectations, we found that in two well-established murine models of experimental RA, CCR2 expression in the hematopoietic cell compartment served as a negative regulator of autoantibody production as well as arthritic disease onset, severity, and resolution. In contrast, the RA phenotype in Ccr5-null mice was similar to that of WT mice. Remarkably, the collagen-induced arthritis phenotype of Cer2(-/-) mice mimicked closely that of severe human RA, including production of rheumatoid factor, enhanced T cell production, and monocyte/macrophage accumulation in the joints. Our findings demonstrate an essential protective role of CCR2 expression in RA, indicate the existence of alternative receptors responsible for monocyte/macrophage accumulation to inflamed joints, and emphasize the need to clarify carefully the complex effects of the chemokine system in RA before they can be considered as therapeutic targets. C1 Univ Texas, Hlth Sci Ctr, Dept Med, MC 7870, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Vet Adm Ctr Res AIDS & HIV 1 Infect, San Antonio, TX USA. Fdn Univ San Martin, Bogota, Colombia. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. RP Ahuja, SK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, MC 7870, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ahuja@uthscsa.edu FU NIAID NIH HHS [AI-48644, R01 AI048644] NR 73 TC 98 Z9 107 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2004 VL 113 IS 6 BP 856 EP 866 DI 10.1172/JCI200420126 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 803ZO UT WOS:000220269200013 PM 15067318 ER PT J AU Elkin, EB Weinstein, KC Winer, EP Kuntz, KM Schnitt, SJ Weeks, JC AF Elkin, EB Weinstein, KC Winer, EP Kuntz, KM Schnitt, SJ Weeks, JC TI HER-2 testing and trastuzurnab therapy for metastatic breast cancer: A cost-effectiveness analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; ARCHIVAL TISSUE SAMPLES; UNITED-STATES FOOD; QUALITY-OF-LIFE; GENE AMPLIFICATION; PROTEIN EXPRESSION; INTEROBSERVER REPRODUCIBILITY; IMMUNOHISTOCHEMICAL ASSAY; RADIATION-THERAPY; IMAGE-ANALYSIS AB Purpose Trastuzumab therapy has been shown to benefit metastatic breast cancer patients whose tumors exhibit HER-2 protein overexpression or gene amplification. Several tests of varying accuracy and cost are available to identify candidates for trastuzumab. We estimated the cost-effectiveness of alternative HER-2 testing and trastuzumab treatment strategies. Patients and Methods We performed a decision analysis using a state-transition model to simulate clinical practice in a hypothetical cohort of 65-year-old metastatic breast cancer patients. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). Interventions included testing with the HercepTest (DAKO, Carpinteria, CA) immunolhistochemical assay alone, fluorescence in situ hybridization (FISH) alone, and both tests, followed by trastuzumab and chemotherapy for patients with positive test results and chemotherapy alone for patients with negative test results. Results In the base case, initial HercepTest with FISH confirmation of all positive results had an ICER of $125,000 per QALY gained. The incremental cost-effectiveness of initial FISH was $145,000 per QALY gained. Other strategies yielded the same or poorer effectiveness at a higher cost, or lower effectiveness at a lower cost, but with a less favorable ICER. These findings persisted under a range of assumptions, and only changes in test characteristics substantially altered results. Conclusion It is more cost-effective to use FISH alone or as confirmation of all positive HercepTest results, rather than using FISH to confirm only weakly positive results or using HercepTest alone. When multiple tests are available to identify treatment candidates, test characteristics may have a substantial impact on the aggregate costs and effectiveness of treatment. (C) 2004 by American Society of Clinical Oncology. C1 Harvard Univ, Ctr Risk Anal, Cambridge, MA 02138 USA. Sch Publ Hlth, Cambridge, England. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Elkin, EB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave,Box 44, New York, NY 10021 USA. EM elkine@mskcc.org FU NLM NIH HHS [T15LM 07092] NR 91 TC 166 Z9 169 U1 0 U2 12 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 MAR 1 PY 2004 VL 22 IS 5 BP 854 EP 863 DI 10.1200/JCO.2004.04.158 PG 10 WC Oncology SC Oncology GA 780KY UT WOS:000189380900015 PM 14990641 ER PT J AU Evins, AE Cather, C Rigotti, NA Freudenreich, O Henderson, DC Olm-Shipman, CM Goff, DC AF Evins, AE Cather, C Rigotti, NA Freudenreich, O Henderson, DC Olm-Shipman, CM Goff, DC TI Two-year follow-up of a smoking cessation trial in patients with schizophrenia: Increased rates of smoking cessation and reduction SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the Society-for-Research-on-Nicotine-and-Tobacco CY FEB 19-22, 2003 CL NEW ORLEANS, LA SP Soc Res Nicotine & Tobacco ID CIGARETTE-SMOKING; MOOD DISORDERS; BUPROPION; SMOKERS AB Background: Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown. This study, conducted between June 2001 and November 2002, evaluated the rate of smoking cessation and reduction in patients with schizophrenia (DSM-IV) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years. Method: Two years following a double-blind placebo-controlled trial of bupropion sustained release, 150 mg/day, added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia, subjects were interviewed, medical charts were reviewed, and carbon monoxide in expired air was measured. Results: Seventeen of 18 subjects completed the follow-up assessment. More subjects were abstinent (22% [N = 4]) at the 2-year follow-up than were abstinent at the end of the trial (6% [N = 1]). Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years (4/7) than those who did not significantly reduce smoking during the trial (0/11) (chi(2) = 8.1, p < .005). Most subjects who achieved greater than or equal to50% reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years. Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up (r = 0.60, p = .01). Conclusion: The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior. We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special populations is indicated. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Schizophrenia Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Evins, AE (reprint author), Freedom Trial Clin, Schizophrenia Res Program, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu FU NIDA NIH HHS [1K23 DA 00510-01]; NIMH NIH HHS [K24 MH 02025] NR 24 TC 56 Z9 57 U1 0 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2004 VL 65 IS 3 BP 307 EP 311 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JJ UT WOS:000222190400004 PM 15096068 ER PT J AU Joliat, MJ Schmidt, ME Fava, M Zhang, SY Michelson, D Trapp, NJ Miner, CM AF Joliat, MJ Schmidt, ME Fava, M Zhang, SY Michelson, D Trapp, NJ Miner, CM TI Long-term treatment outcomes of depression with associated anxiety: Efficacy of continuation treatment with fluoxetine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANXIOUS DEPRESSION; MAJOR DEPRESSION; ELDERLY PATIENTS; FOLLOW-UP; SERTRALINE; REMISSION; DISORDER; SYMPTOMS; RELAPSE; PLACEBO AB Background: Severity of anxiety does not appear to influence the antidepressant response to fluoxetine during acute treatment of major depressive disorder (MDD). We report a retrospective pooled analysis of 2 studies to assess the effect of associated anxiety on the efficacy of fluoxetine in the continuation treatment phase of MDD. Method: Patients whose MDD remitted (study 1) or responded (study 2) after approximately 12 to 13 weeks of open-label treatment with fluoxetine 20 mg daily were randomly assigned in double-blind fashion to placebo, continued treatment with fluoxetine 20 mg daily, or, in study 2 only, treatment with enteric-coated fluoxetine 90 mg once weekly, for at least 25 weeks. Both studies included male and female outpatients who met criteria for MDD as assessed by DSM-III-R (study 1) or DSM-IV (study 2). Patients were categorized into high anxiety (greater than or equal to 7) or low anxiety (< 7) subgroups based on baseline Hamilton Rating Scale for Depression (HAM-D) anxiety/ somatization subfactor scores. Subgroups were compared by therapy for time from randomization to relapse and change in efficacy scores. Results: No significant differences in time to relapse were observed between anxiety subgroups in either active treatment group. However, in patients switched to placebo for continuation treatment, the high anxiety subgroup had a significantly higher risk of relapse than those with low anxiety (risk ratio = 1.63, p = .013). Significant differences between anxiety groups were seen in change in HAM-D anxiety/somatization subfactor scores in the fluoxetine 20 mg and placebo treatment groups, and in change in HAM-D-17 scores in the placebo treatment group (p < .05). Conclusion: Although high baseline anxiety does not appear to impact the benefit of continuation therapy with fluoxetine, it does appear to predict increased risk of relapse in individuals who do not remain on antidepressant therapy for the duration of continuation treatment. C1 Eli Lilly & Co, Lilly Res Labs, NE Harbor, ME 04662 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Joliat, MJ (reprint author), Eli Lilly & Co, Lilly Res Labs, POB 812, NE Harbor, ME 04662 USA. EM joliat@lilly.com RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 25 TC 5 Z9 6 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2004 VL 65 IS 3 BP 373 EP 378 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 831JJ UT WOS:000222190400013 PM 15096077 ER PT J AU Elashoff, M Ryan, L AF Elashoff, M Ryan, L TI An EM algorithm for estimating equations SO JOURNAL OF COMPUTATIONAL AND GRAPHICAL STATISTICS LA English DT Article DE generalized estimating equations; missing data ID GENERALIZED ESTIMATING EQUATIONS; MAXIMUM-LIKELIHOOD; REGRESSION-MODELS; LONGITUDINAL DATA; QUASI-LIKELIHOOD; COVARIATE DATA; MISSING DATA; DISCRETE AB This article presents an algorithm for accommodating missing data in situations where a natural set of estimating equations exists for the complete data setting. The complete data estimating equations can correspond to the score functions from a standard, partial, or quasi-likelihood, or they can be generalized estimating equations (GEEs). In analogy to the EM, which is a special case, the method is called the ES algorithm, because it iterates between an E-Step wherein functions of the complete data are replaced by their expected values, and an S-Step where these expected values are substituted into the complete-data estimating equation, which is then solved. Convergence properties of the algorithm are established by appealing to general theory for iterative solutions to nonlinear equations. In particular, the ES algorithm (and indeed the EM) are shown to correspond to examples of nonlinear Gauss-Seidel algorithms. An added advantage of the approach is that it yields a computationally simple method for estimating the variance of the resulting parameter estimates. C1 Gene Log, Biostat, Germantown, MD 20876 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Elashoff, M (reprint author), Gene Log, Biostat, 11124 Yellow Leaf Way, Germantown, MD 20876 USA. EM MElashoff@genelogic.com; lryan@hsph.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 31 TC 14 Z9 14 U1 0 U2 5 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 1061-8600 J9 J COMPUT GRAPH STAT JI J. Comput. Graph. Stat. PD MAR PY 2004 VL 13 IS 1 BP 48 EP 65 DI 10.1198/1061860043092 PG 18 WC Statistics & Probability SC Mathematics GA 802RZ UT WOS:000220181900004 ER PT J AU Borowski, C Li, XY Aifantis, I Gounari, F von Boehmer, H AF Borowski, C Li, XY Aifantis, I Gounari, F von Boehmer, H TI Pre-TCR alpha and TCR alpha are not interchangeable partners of TCR beta during T lymphocyte development SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T lymphocyte subsets; cell lineage; receptor-mediated signal transduction; receptor antigen; T-cell gamma delta ID NF-KAPPA-B; CELL-RECEPTOR; PT-ALPHA; CYTOPLASMIC TAIL; EXPRESSION; GENE; ACTIVATION; CHAIN; INTERNALIZATION; DEGRADATION AB In contrast with the alphabeta T cell receptor (TCK), the pre-TCR spontaneously segregates to membrane rafts from where it signals in a cell-autonomous fashion. The disparate behaviors of these two receptors may stem either from differences inherent to the distinct developmental stages during which they are expressed, or from features intrinsic and unique to the receptor components themselves. Here, we express TCRalpha precisely at the pre-TCR checkpoint, at levels resembling those of endogenous pre-TCRalpha (pTalpha), and in the absence of endogenous pTalpha. Both in isolation and more dramatically when in competition with pTalpha, TCRalpha induced defective proliferation, survival, and differentiation of alphabeta T lymphocyte precursors, as well as impaired commitment to the alphabeta T lymphocyte lineage. Substitution of TCRalpha transmembrane and cytoplasmic domains with those of pTalpha generated a hybrid molecule possessing enhanced competitive abilities. We conclude that features intrinsic to the pre-TCR, which are absent in TCRalpha, are essential for its unique function. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Smith Bldg,Room 736,1 Jimmy Fund Way, Boston, MA 02115 USA. EM harald_von_Boehmer@dfci.harvard.edu FU NIAID NIH HHS [R01 AI045846, AI45846, R01 AI047281, AI47281] NR 29 TC 41 Z9 42 U1 0 U2 2 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 MAR 1 PY 2004 VL 199 IS 5 BP 607 EP 615 DI 10.1084/jem.20031973 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 801UR UT WOS:000220121300002 PM 14993248 ER PT J AU Cook, JM Riggs, DS Thompson, R Coyne, JC Sheikh, JI AF Cook, JM Riggs, DS Thompson, R Coyne, JC Sheikh, JI TI Posttraumatic stress disorder and current relationship functioning among World War II ex-prisoners of war SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article ID VIETNAM COMBAT VETERANS; FORMER PRISONERS; FOLLOW-UP; MENTAL-HEALTH; PTSD; CONFLICT; MARRIAGE; QUALITY; ADJUSTMENT; EXPERIENCE AB This study examined the association of posttraumatic stress disorder (PTSD) with the quality of intimate relationships among present-day male World War II ex-prisoners of war (POWs). Ex-POWs had considerable marital stability; those with PTSD were no less likely to be in an intimate relationship. Ex-POWs in an intimate relationship who had PTSD (N = 125) were compared with ex-POWs in a relationship who did not have PTSD (N = 206). Marital functioning was within a range expected for persons without traumatic exposure. Yet, over 30% of those with PTSD reported relationship problems compared with only 11% of those without PTSD. Ex-POWs with PTSD reported poorer adjustment and communication with their partners and more difficulties with intimacy. Emotional numbing was significantly associated with relationship difficulties independent of other symptom complexes and severity of PTSD. Implications for clinical practice are discussed. C1 Univ Penn, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. VA Palo Alto Med Ctr, Dept Psychiat & Behav Sci, Palo Alto, CA USA. Stanford Univ, Stanford, CA 94305 USA. RP Cook, JM (reprint author), Univ Penn, Treatment Res Ctr, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM cook_j@mail.trc.upenn.edu RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X NR 54 TC 107 Z9 107 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD MAR PY 2004 VL 18 IS 1 BP 36 EP 45 DI 10.1037/0893-3200.18.1.36 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 800PA UT WOS:000220039000004 PM 14992608 ER PT J AU Stelzner, M AF Stelzner, M TI 2003 SSAT-AGA-ASGE Workshop on "Palliative Therapy of Rectal Cancer" - Summary statement SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Univ Washington, Dept Surg, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. RP Stelzner, M (reprint author), Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles, 10H2-MS,11301 Wilshire Blv, Los Angeles, CA 90073 USA. EM matthias.stelzner@med.va.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 2004 VL 8 IS 3 BP 253 EP 258 DI 10.1016/j.gassur.2003.11.021 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 806EI UT WOS:000220416800007 PM 15019917 ER PT J AU Willett, CG Gunderson, LL AF Willett, CG Gunderson, LL TI Palliative treatment of rectal cancer: Is radiotherapy alone a good option? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 18-21, 2003 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract DE rectal cancer; radiation therapy; intraoperative radiation therapy ID RECURRENT COLORECTAL-CANCER; RADIATION-THERAPY; RECTOSIGMOID CANCER; CARCINOMA; SURGERY; IRRADIATION; COLON C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mayo Clin, Dept Radiat Oncol, Scottsdale, AZ USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM willett.christopher@mgh.harvard.edu NR 18 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 2004 VL 8 IS 3 BP 277 EP 279 DI 10.1016/j.gassur.2003.11.015 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 806EI UT WOS:000220416800013 PM 15019923 ER PT J AU Harness, NG Mankin, HJ AF Harness, NG Mankin, HJ TI Giant-cell tumor of the distal forearm SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE giant cell tumor; radius; ulna ID ALLOGRAFT REPLACEMENT; FOLLOW-UP; BONE; RADIUS; EXCISION; BENIGN; RECONSTRUCTION; RECURRENCE; METASTASES; GRAFT AB Purpose: Many authorities express concern that giant-cell tumors of the distal forearm are more frequently recurrent and difficult to treat chiefly because of the proximity to the carpus and the resultant diminished range of motion in the hand and forearm. We have studied the results from our institution for 49 patients with giant-cell tumors of the distal forearm treated from 2 to 28 years (mean, 14 +/- 7 years) and compared the results for different methods of treatment. Methods: Through the computer database 49 patients with giant-cell tumors of the distal forearm (46 of the radius, 3 of the ulna) were identified. By using material from patient visits, chart review, and when necessary telephone interviews it was possible to gather demographic and outcome data for the 49 patients. For the radial lesions, 15 of the patients had a marginal resection of the distal radius along with the periosteum and ligamentous structures and implantation of cadaveric allografts. Twenty-six patients had intralesional curettage and insertion of polymethylmethacrylate (PMMA) and 5 had curettage and autograft insertion. The 3 patients with ulnar lesions were treated with Darrach resections. Results: There were no deaths, infections, metastases, or amputations. In addition to the 49 original surgeries, the patients required 41 additional surgical procedures, 17 of which were for recurrent disease. The greatest numbers of recurrences were in the patients who underwent curettage with autograft or PMMA implantation. Only 2 recurrences were in patients who had a marginal resection and implantation of cadaveric allografts. The overall results for the patients showed that many had mostly minor complaints referable to function or pain and that only 18 of the 49 patients were asymptomatic. Conclusions: Although the patients with distal forearm giant-cell tumors have had a difficult course in terms of local recurrence and subsequent surgeries required for treatment failures, the ultimate outcomes for both allograft transplantation and curettage and insertion of PMMA are satisfactory. The patients with complete distal radial allografts had a better record for prevention of recurrence than the patients treated with curettage and PMMA insertion but the percentages of currently asymptomatic patients are approximately the same for both series (40% [6/15], 35% [9/26]). These data support the concept that marginal resection and complete distal radial allograft implantation should be used for patients with tumors that have destroyed much of the bone and have extensive soft tissue components and that curettage and PMMA insertion should be reserved for patients where the structural alteration of the bone is minimal. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Serv, Orthopaed Gray 6, Boston, MA 02114 USA. NR 30 TC 38 Z9 42 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2004 VL 29A IS 2 BP 188 EP 193 DI 10.1016/j.jhsa.2003.11.003 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 805JH UT WOS:000220362100002 PM 15043887 ER PT J AU Cornwall, R Koris, MJ Jupiter, JB AF Cornwall, R Koris, MJ Jupiter, JB TI Wrist joint ganglion presenting as a painless mass in the palm: Report of 2 cases SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE ganglion; mass; tumor; palm ID MEDIAN NERVE; CARPAL-TUNNEL; MOTOR BRANCH; HAND; COMPRESSION; NEUROPATHY; FINGERS; CYSTS AB Ganglions occur commonly in the wrist and arise from the radiocarpal and intercarpal joints. Although ganglions present commonly as masses on the dorsal or volar surface of the wrist, ganglions from wrist joints appear rarely at other locations in the hand. We report 2 cases of ganglions arising from wrist joints that presented as painless masses in the center of the palm without signs or symptoms of median or ulnar nerve compression. Surgical treatment required extensile exposure to trace the proximal stalks to their joints of origin. Knowledge of the possibility that a painless mass in the palm could be a ganglion arising from a joint in the wrist allows proper presurgical planning and informed consent. Copyright (C) 2004 by the American Society for Surgery of the Hand. C1 Childrens Hosp Philadelphia, Div Orthopaed, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Orthopaed, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Cornwall, R (reprint author), Childrens Hosp Philadelphia, Div Orthopaed, 34th St & Civiv Ctr Blvd, Philadelphia, PA 19104 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2004 VL 29A IS 2 BP 289 EP 292 DI 10.1016/j.jhsa.2003.11.006 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 805JH UT WOS:000220362100018 PM 15043903 ER PT J AU Emmons, KM Wong, M Puleo, E Weinstein, N Fletcher, R Colditz, G AF Emmons, KM Wong, M Puleo, E Weinstein, N Fletcher, R Colditz, G TI Tailored computer-based cancer risk communication: Correcting colorectal cancer risk perception SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID BREAST-CANCER; INTERVENTIONS; PREVENTION; DECISIONS; BEHAVIOR; INDEX AB We developed a computer-based tailored risk presentation and risk communication aid for colorectal cancer prevention. To evaluate the effectiveness of the tool, we randomized 353 participants to receive different risk presentation formats (relative plus absolute risk vs. absolute risk only vs. none) and different levels of engagement with the risk communication (active vs. passive). Findings suggest the tool to be useful for correcting misperceptions about personal risk. Of those with inaccurate risk perception at baseline, more than half of the participants in intervention groups had corrected risk perceptions at post-test, compared to only 12% in the control group. C1 Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Amherst, MA 01003 USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Harvard Pilgrim Hlth Care, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, 44 Binney St, Boston, MA 02115 USA. EM karen_m_emmons@dfci.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [5P30 CA06516-40, T32 CA09001-25] NR 32 TC 39 Z9 39 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD MAR-APR PY 2004 VL 9 IS 2 BP 127 EP 141 DI 10.1080/10810730490425295 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 810YK UT WOS:000220739400006 PM 15204824 ER PT J AU Marks, JP Reed, W Colby, K Ibrahim, SA AF Marks, JP Reed, W Colby, K Ibrahim, SA TI A culturally competent approach to cancer news and education in an inner city community: Focus group findings SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID RACIAL-DIFFERENCES; HEALTH BELIEFS; BREAST-CANCER; ATTITUDES; KNOWLEDGE; WOMEN; MAMMOGRAPHY; RISK; CARE AB Ethnic minorities who live in socioeconomically disenfranchised communities suffer disproportionately from many health problems including cancer. In an effort to reduce these disparities, many health-care practitioners and scholars have promoted "culturally competent" health education efforts. One component of culturally competent eudcation is a grounded knowledge base. To obtain knowledge about the cancer-related ideas of members of one African American community, researchers conducted focus groups with public housing residents and used the findings to develop a five-part television news series about breast, prostate, and cervix cancers. We found that participants gathered information from the folk, popular, and professional health sectors and constructed their cancer-related ideas from this information. Furthermore, experiences of racism, sexism, and classism colored their beliefs and behaviors regarding the prevention, detection, and treatment of common cancers. For this community "cancer" represents a giant screen upon which individual fears and societal ethnic, political, and economic tensions are projected. C1 Publ Hlth Prod Inc, Cleveland, OH 44118 USA. Cleveland State Univ, Urban Child Res Ctr, Cleveland, OH 44115 USA. VA Pittsburgh Hlth Care Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Marks, JP (reprint author), Publ Hlth Prod Inc, 2192 Briarwood Rd, Cleveland, OH 44118 USA. EM phpjpmarks@peoplepc.com NR 40 TC 13 Z9 13 U1 2 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD MAR-APR PY 2004 VL 9 IS 2 BP 143 EP 157 DI 10.1080/10810730490425303 PG 15 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 810YK UT WOS:000220739400007 PM 15204825 ER PT J AU Zippelius, A Bioley, G Le Gal, FA Rufer, N Brandes, M Batard, P De Smedt, M Plum, J Speiser, DE Cerottini, JC Dietrich, PY Romero, P Pittet, MJ AF Zippelius, A Bioley, G Le Gal, FA Rufer, N Brandes, M Batard, P De Smedt, M Plum, J Speiser, DE Cerottini, JC Dietrich, PY Romero, P Pittet, MJ TI Human thymus exports naive CD8 T cells that can home to nonlymphoid tissues SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SECONDARY LYMPHOID ORGANS; CLONAL EXPANSIONS; LYMPHOCYTES; MIGRATION; DIFFERENTIATION; RECIRCULATION; CHEMOKINES; REPERTOIRE; MECHANISMS; EMIGRATION AB Functionally naive CD8 T cells in peripheral blood from adult humans can be fully described by their CD45RA(bright)CCR7(+)CD62L(+) cell surface phenotype. Cord blood lymphocytes, from healthy newborns, are homogenously functionally naive. Accordingly, the majority of cord blood CD8 T cells express the same pattern of cell surface molecules. Unexpectedly, however, a significant fraction of cord blood CD8 T cells express neither CCR7 nor CD62L. Yet these cells remain functionally naive as they contain high levels of TCR excision circles, have long telomeres, display highly polyclonal TCRs, and do not exhibit immediate effector functions. In addition, these CD8 T cells already represent a significant fraction of the mature naive CD8 single-positive thymocyte repertoire and may selectively express the cutaneous lymphocyte Ag. We suggest that CD8 single-positive thymocytes comprise two pools of naive precursors that exhibit distinct homing properties. Once seeded in the periphery, naive CCR7(+)CD62L(+) CD8 T cells patrol secondary lymphoid organs, whereas naive CCR7(-)CD62L(-) CD8 T cells selectively migrate to peripheral tissues such as skin. C1 Univ Hosp, Ludwig Inst Canc Res, Div Clin Oncoimmunol, Lausanne, Switzerland. Univ Hosp, Div Oncol, Lab Tumor Immunol, Geneva, Switzerland. Swiss Inst Expt Canc Res, Natl Ctr Competence Res Mol Oncol, CH-1066 Epalinges, Switzerland. Univ Bern, Theodor Kocher Inst, Bern, Switzerland. Univ Hosp, Dept Clin Chem Microbiol & Immunol, Ghent, Belgium. Univ Lausanne, Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland. RP Pittet, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM inpittet@hms.harvard.edu RI Plum, Jean/A-4357-2008; Speiser, Daniel/F-2173-2013 NR 27 TC 15 Z9 15 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2004 VL 172 IS 5 BP 2773 EP 2777 PG 5 WC Immunology SC Immunology GA 777PD UT WOS:000189186000011 PM 14978076 ER PT J AU Chien, PC Chen, D Chen, PD Tuen, M Cohen, S Migueles, SA Connors, M Rosenberg, E Malhotra, U Gonzalez, C Hioe, CE AF Chien, PC Chen, D Chen, PD Tuen, M Cohen, S Migueles, SA Connors, M Rosenberg, E Malhotra, U Gonzalez, C Hioe, CE TI HIV-1-Infected patients with envelope-specific lymphoproliferation or long-term nonprogression lack antibodies suppressing glycoprotein 120 antigen presentation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Keystone Symposium on Twenty Years of HIV Research from Discovery to Understanding CY MAR 28-APR 03, 2003 CL BANFF, CANADA ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; CD4(+) T-CELLS; DISEASE PROGRESSION; HIV-1 INFECTION; HUMORAL RESPONSES; BINDING DOMAIN; GP120; NEUTRALIZATION; GLYCOSYLATION AB Background. Antibodies to the CD4-binding domain (CD4bd) of human immunodeficiency virus type 1 (HIV-1) glycoprotein 120 (gp120) inhibit gp120 antigen presentation to CD4 T cells. These findings imply that the presence of anti-CD4bd antibodies might contribute to the dearth of envelope-specific T helper responses observed in most HIV-1-positive patients. In the absence of these antibodies, however, anti-envelope T helper responses might be maintained. Methods. We used ELISA to evaluate the levels of anti-CD4bd antibodies in rare HIV-1-positive patients who exhibit envelope-specific lymphoproliferation. Subsequently, we examined the contribution of anti-CD4bd antibodies to disease progression by comparing anti-CD4bd antibody levels in 3 cohorts of HIV-1-positive patients with distinct rates of disease progression. Results. Although most HIV-1-positive individuals produce anti-CD4bd antibodies, 77% of patients with envelope-specific lymphoproliferation have undetectable anti-CD4bd antibody levels. Moreover, comparison of the 3 HIV-1-positive cohorts revealed that individuals with long-term nonprogression have significantly lower anti-CD4bd antibody titers than do those with rapid or slow progression. Unlike immunoglobulin G (IgG) from rapid progressors, IgG from nonprogressors had no suppressive effects on glycoprotein (gp) 120-specific T cell proliferation. Conclusions. Low anti-CD4bd antibody levels are associated with the absence of disease progression. A number of HIV-1-positive individuals without these antibodies also appear to sustain gp120-specific T helper responses needed to help control the infection. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Program Infect Dis, Seattle, WA 98104 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. NYU, Sch Med, Dept Pathol, New York, NY USA. RP Hioe, CE (reprint author), Vet Adm Med Ctr, 423 E 23rd St,Rm 18-24 N, New York, NY 10010 USA. EM catarina.hioe@med.nyu.edu FU NIAID NIH HHS [AI-01550, AI-48371, AI-27742, AI-27757] NR 35 TC 7 Z9 7 U1 0 U2 0 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 MAR 1 PY 2004 VL 189 IS 5 BP 852 EP 861 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800AI UT WOS:000220000900014 PM 14976603 ER PT J AU Ludwig, RJ Schultz, JE Boehncke, WH Podda, M Tandi, C Krombach, F Baatz, H Kaufmann, R von Andrian, UH Zollner, TM AF Ludwig, RJ Schultz, JE Boehncke, WH Podda, M Tandi, C Krombach, F Baatz, H Kaufmann, R von Andrian, UH Zollner, TM TI Activated, not resting, platelets increase leukocyte rolling in murine skin utilizing a distinct set of adhesion molecules SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE adhesion molecules; homing; inflammation; platelets; psoriasis; skin ID OCCLUSIVE VASCULAR-DISEASE; SELECTIN-DEFICIENT MICE; P-SELECTIN; ENDOTHELIAL-CELLS; PSORIATIC PATIENTS; GLYCOPROTEIN-IB; CUTANEOUS INFLAMMATION; EXPRESSION; ICAM-1; MONOCYTES AB Selectin-mediated tethering and rolling initiates the multi-step process of leukocyte extravasation which is crucial for the formation of an inflammatory infiltrate. We studied the impact of platelets on this process in the skin. Using intravital microscopy, we analyzed platelet interactions with cutaneous post-capillary venules of mouse ears and observed an increase in platelet rolling if platelets were activated (41.6 +/- 20.2% vs. 13.1 +/- 8.5% rolling of resting platelets). Experiments with P-selectin deficient mice and antibodies blocking either P-selectin, GPIIb/IIIa or GPIb showed that rolling depends on platelet PSGL-1 and GPIIb/IIIa on one hand, and endothelial P-selectin on the other. Next, formation of platelet-leukocyte aggregates was demonstrated by simultaneous observation of platelets and leukocytes in vivo utilizing a newly developed two-color technique. Aggregates increased overall leukocyte rolling (leukocytes alone: 27.4 +/- 11.2%, leukocytes with resting platelets: 25.3 +/- 10.2%, leukocytes with activated platelets 38.1 +/- 11.8%). To investigate if activated platelets may contribute to the pathogenesis of chronic cutaneous inflammation, platelet P-selectin expression was studied in 8 patients with psoriasis. A correlation between platelet P-selectin expression and disease severity was established. In summary, we show that activated, not resting, platelets increase leukocyte rolling in murine skin. This increased rolling is due to the aggregate formation of platelets with leukocytes. We also provide evidence for a potential role of this mechanism in the pathogenesis of chronic inflammatory skin diseases. C1 Univ Frankfurt, Dept Dermatol, D-60590 Frankfurt, Germany. Schering AG, RBA Dermatol, D-1000 Berlin, Germany. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Frankfurt, Dept Opthacuol, D-6000 Frankfurt, Germany. Univ Munich, Inst Surg Res, D-8000 Munich, Germany. RP Ludwig, RJ (reprint author), Univ Frankfurt, Dept Dermatol, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM r.ludwig@em.uni-frankfurt.de RI Ludwig, Ralf/A-2629-2008; von Andrian, Ulrich/A-5775-2008 OI Ludwig, Ralf/0000-0002-1394-1737; NR 43 TC 80 Z9 81 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 BP 830 EP 836 DI 10.1111/j.0022-202X.2004.22318.x PG 7 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500042 PM 15086572 ER PT J AU Angle-Zahn, A Koo, S Kim, Y Bradner, J Longo, I Nghiem, P AF Angle-Zahn, A Koo, S Kim, Y Bradner, J Longo, I Nghiem, P TI The role of ATR and the replication checkpoint in vitro and in vivo in skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Charlestown, MA USA. Cutaneous Biol Res Ctr, Charlestown, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 BP A21 EP A21 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500175 ER PT J AU Astner, S Cheung, AC Gonzalez, E Rius-Diaz, F Doukas, AG Gonzalez, S AF Astner, S Cheung, AC Gonzalez, E Rius-Diaz, F Doukas, AG Gonzalez, S TI The sensitivity and specificity of confocal microscopy in the diagnosis of allergic contact dermatitis: a preliminary study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Boston, MA USA. Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 280 BP A47 EP A47 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500331 ER PT J AU Chren, M Sahay, A Bertenthal, D AF Chren, M Sahay, A Bertenthal, D TI Quality-of-life outcomes of treatments for nonmelanoma skin cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Calif San Francisco, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 380 BP A64 EP A64 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500432 ER PT J AU Gupta, SG Wang, LC Longo, M Kulke, MH Nghiem, P AF Gupta, SG Wang, LC Longo, M Kulke, MH Nghiem, P TI Merkel cell carcinoma (MCC): a novel treatment for stage III disease and a proposed algorithm for initial management SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 307 BP A52 EP A52 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500357 ER PT J AU Hirakawa, S Fujii, S Kajiya, K Yano, K Detmar, M AF Hirakawa, S Fujii, S Kajiya, K Yano, K Detmar, M TI Enhanced acute photosensitivity and chronic UVB-induced cutaneous photodamage in VEGF transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Charlestown, MA USA. Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 024 BP A4 EP A4 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500077 ER PT J AU Hong, Y Foreman, K Shin, J Hirakawa, S Curry, CL Sage, DR Liberman, T Dezube, BJ Fingeroth, JD Detmar, M AF Hong, Y Foreman, K Shin, J Hirakawa, S Curry, CL Sage, DR Liberman, T Dezube, BJ Fingeroth, JD Detmar, M TI Lymphatic reprogramming of blood vascular endothelial cells by Kaposi's sarcoma-associated herpes virus SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 792 BP A132 EP A132 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500841 ER PT J AU Jin, JH Zhang, W Werth, VP AF Jin, JH Zhang, W Werth, VP TI Thalidomide inhibits the induction of tumor necrosis factor-alpha by ultraviolet B irradiation of human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 038 BP A7 EP A7 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500093 ER PT J AU Kunstfeld, R Hirakawa, S Hong, Y Lange-Asschenfeldt, B Velasco, P Fiebiger, E Wu, Y Hicklin, D Bohlen, P Detmar, M AF Kunstfeld, R Hirakawa, S Hong, Y Lange-Asschenfeldt, B Velasco, P Fiebiger, E Wu, Y Hicklin, D Bohlen, P Detmar, M TI VEGF-A induced psoriatic skin inflammation and the associated lymphangiogenic response are ameliorated by systemic blockage of VEGF receptor-1 and-2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Imclone Syst Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 009 BP A2 EP A2 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500061 ER PT J AU Li, J Baxter, RM Weiner, L Goetinck, P Calautti, E Brissette, JL AF Li, J Baxter, RM Weiner, L Goetinck, P Calautti, E Brissette, JL TI Foxn 1 promotes epithelial morphogenesis by modulating protein kinase C SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 625 BP A105 EP A105 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500675 ER PT J AU Ming, ME Van Belle, P Xu, X Mihm, MC Hotz, S Botbyl, JD Elder, DE Elenitsas, R Guerry, D Gimotty, PA AF Ming, ME Van Belle, P Xu, X Mihm, MC Hotz, S Botbyl, JD Elder, DE Elenitsas, R Guerry, D Gimotty, PA TI TIA-1-positive lymphocytes are associated with metastases in patients with melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 369 BP A62 EP A62 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500418 ER PT J AU Mitsumoto, A Choi, W Kochevar, IE AF Mitsumoto, A Choi, W Kochevar, IE TI Role of reactive oxygen species in TGF-beta 1-induced tropoelastin gene expression in dermal fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 197 BP A33 EP A33 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500246 ER PT J AU Nahm, WK Morhenn, VB Moy, RL Falanga, V AF Nahm, WK Morhenn, VB Moy, RL Falanga, V TI Characteristics of whole-cell patch clamping in cultured human keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Calif San Diego, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, San Diego, CA USA. Boston Univ, Sch Med, Roger Williams Med Ctr, Providence, RI USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 565 BP A95 EP A95 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500615 ER PT J AU Nlhal, M Mukhtar, H Wood, GS AF Nlhal, M Mukhtar, H Wood, GS TI Epigallocatechin-3-gallate (EGCG) causes cell cycle arrest and apoptosis in human melanoma cells via modulation of the cyclin kinase inhibitor (cki)-cyclin dependent kinase (cdk) network and Bcl2 family proteins SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Wisconsin, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 941 BP A157 EP A157 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500987 ER PT J AU Okuyama, R Nguyen, B Talora, C Lioumi, M Chiorino, G Ogawa, E Tagami, H Woo, M Dotto, PG AF Okuyama, R Nguyen, B Talora, C Lioumi, M Chiorino, G Ogawa, E Tagami, H Woo, M Dotto, PG TI High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Tohoku Univ, Grad Sch Med, Dept Dermatol, Sendai, Miyagi 980, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Lab Canc Pharmacogen, Biella, Italy. Ontario Canc Inst, Dept Med, Toronto, ON M4X 1K9, Canada. Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 651 BP A109 EP A109 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500700 ER PT J AU Perlis, CS Perlis, RH AF Perlis, CS Perlis, RH TI Prevalence and impact of industry funding of dermatology clinical trials SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Brown Univ, Sch Med, Dept Dermatol, Providence, RI USA. Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA USA. Univ Penn, Dept Bioeth, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 373 BP A63 EP A63 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500423 ER PT J AU Rhim, E Reiber, GE Smith, DG Raugi, GJ Sullivan, K AF Rhim, E Reiber, GE Smith, DG Raugi, GJ Sullivan, K TI Foot ulcers in people with diabetes: signs of infection are the major determinant for use of cultures, antibiotics and x-rays and are associated with amputation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care, Hlth Serv & Epidemiol, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 309 BP A52 EP A52 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500358 ER PT J AU Schacht, V Dadras, SS Johnson, L Jackson, DG Hong, YK Detmar, M AF Schacht, V Dadras, SS Johnson, L Jackson, DG Hong, YK Detmar, M TI Up-regulation of the lymphatic marker podoplanin in human squamous cell carcinomas and germ cell tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DU, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 101 BP A17 EP A17 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500152 ER PT J AU Shimizu, H Morgan, BA AF Shimizu, H Morgan, BA TI Recapitulation of the hair cycle in dermal papilla cells in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Nihon Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 636 BP A106 EP A106 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500686 ER PT J AU Strasswimmer, J Pierce, MC Park, B deBoer, JF AF Strasswimmer, J Pierce, MC Park, B deBoer, JF TI Optical coherence tomography (OCT) for noninvasive quantification of dermal ageing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 848 BP A142 EP A142 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500898 ER PT J AU Velasco, P Huegel, R Harder, J Christophers, E Schroder, JM Lawler, J Detmar, M Lange-Asschenfeldt, B AF Velasco, P Huegel, R Harder, J Christophers, E Schroder, JM Lawler, J Detmar, M Lange-Asschenfeldt, B TI Thrombospondin 1 modulates inflammation and vascular remodeling during experimental delayed-type hypersensitivity reactions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Univ Kiel, Dept Dermatol, SH, D-2300 Kiel, Germany. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RI Schroeder, Jens/B-3994-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 020 BP A4 EP A4 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500075 ER PT J AU Weiner, L Han, R Scicchitano, BM Lee, D Brissette, JL AF Weiner, L Han, R Scicchitano, BM Lee, D Brissette, JL TI The Foxn1 transcription factor converts epithelial cells into targets for pigmentation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 920 BP A154 EP A154 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500970 ER PT J AU Wertheimer, E Sizyakov, G Takeda, J Kahn, C Tennenbaum, T Shapira, R AF Wertheimer, E Sizyakov, G Takeda, J Kahn, C Tennenbaum, T Shapira, R TI Insulin signaling is essential for proper wound healing of skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Tel Aviv Sackler Med Sch, Tel Aviv, Israel. Osaka Univ, Osaka, Japan. Joslin Diabet Ctr, Boston, MA 02215 USA. Bar Ilan Univ, Ramat Gan, Israel. Shaarey Tzedek Hosp, Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 610 BP A102 EP A102 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500661 ER PT J AU Yamashita, T Akita, H Lerner, E Takahashi, M Gonzalez, S AF Yamashita, T Akita, H Lerner, E Takahashi, M Gonzalez, S TI Confocal microscopy study of the effects of UVA radiation on the skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 28-MAY 01, 2004 CL Providence, RI SP Soc Investigat Dermatol C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Shiseido Res Ctr, Yokohama, Kanagawa, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2004 VL 122 IS 3 MA 817 BP A137 EP A137 PG 1 WC Dermatology SC Dermatology GA 809UB UT WOS:000220660500866 ER PT J AU Dougherty, RH Rohrer, JL Hayden, D Leder, BZ AF Dougherty, RH Rohrer, JL Hayden, D Leder, BZ TI Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly hypogonadal men: A double blind placebo controlled randomized trial. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern Section of the American-Federation-for-Medical-Research CY APR 15, 2004 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwest Sect C1 Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2004 VL 52 IS 2 BP S390 EP S390 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 806EH UT WOS:000220416700164 ER PT J AU Florez, JC Burtt, N de Bakker, PW Almgren, P Tuomi, T Holmkvist, J Gaudet, D Hudson, TJ Schaffner, SF Daly, MJ Hirschhorn, JN Groop, L Altshuler, D AF Florez, JC Burtt, N de Bakker, PW Almgren, P Tuomi, T Holmkvist, J Gaudet, D Hudson, TJ Schaffner, SF Daly, MJ Hirschhorn, JN Groop, L Altshuler, D TI Haplotype structure and association of common variants in the gene encoding the islet ATP-sensitive potassium channel with type 2 diabetes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern Section of the American-Federation-for-Medical-Research CY APR 15, 2004 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwest Sect C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Schaffner, Stephen/D-1189-2011; Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2004 VL 52 IS 2 BP S384 EP S384 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 806EH UT WOS:000220416700131 ER PT J AU Williams, JS Williams, GH Jeunemaitre, X Hopkins, PN Conlin, PR AF Williams, JS Williams, GH Jeunemaitre, X Hopkins, PN Conlin, PR TI Influence of dietary sodium on the renin-angiotensin-aldosterone system and prevalence of left ventricular hypertrophy by EKG criteria. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern Section of the American-Federation-for-Medical-Research CY APR 15, 2004 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwest Sect C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop European Georges Pompidou, Ctr Invest Clin, INSERM, Dept Genet, F-92401 Paris, France. Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2004 VL 52 IS 2 BP S385 EP S385 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 806EH UT WOS:000220416700138 ER PT J AU Wolf, M Hubel, CA Seely, EW Roberts, JM Sukhatme, VP Karumanchi, SA Thadhani, R AF Wolf, M Hubel, CA Seely, EW Roberts, JM Sukhatme, VP Karumanchi, SA Thadhani, R TI Preeclampsia and future cardiovascular disease: Potential role of altered angiogenesis and insulin resistance. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Combined Annual Meeting of the Central-Society-for-Clinical-Research/Midwestern Section of the American-Federation-for-Medical-Research CY APR 15, 2004 CL Chicago, IL SP Cent Soc Clin Res, Amer Federat Med Res, Midwest Sect C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Renal Unit, Boston, MA 02115 USA. Magee Womens Res Inst, Renal Unit, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2004 VL 52 IS 2 BP S382 EP S383 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 806EH UT WOS:000220416700123 ER PT J AU Chalfant, CE Szulc, Z Roddy, P Bielawska, A Hannun, YA AF Chalfant, CE Szulc, Z Roddy, P Bielawska, A Hannun, YA TI The structural requirements for ceramide activation of serine-threonine protein phosphatases SO JOURNAL OF LIPID RESEARCH LA English DT Article DE protein phosphatase-2A; protein phosphatase-1; ceramide-activated protein phosphatase ID KINASE-C-ZETA; SPHINGOLIPID BREAKDOWN PRODUCTS; D-ERYTHRO-SPHINGOSINE; CELL-DIFFERENTIATION; SIGNAL-TRANSDUCTION; MEDIATED BIOLOGY; BINDING; DEPHOSPHORYLATION; INHIBITION; SUBSTRATE AB The protein phosphatases1 (PP1) and 2A (PP2A) serve as ceramide-activated protein phosphatases (CAPP). In this study, the structural requirements for interaction between ceramide and CAPP were determined. D-erythro-C-6 ceramide activated the catalytic subunit of PP2A (PP2Ac) approximately 3-fold in a stereospecific manner. In contrast, saturation of the 4-5 double bond, producing D-erythro-dihydro C-6 ceramide, inhibited PP2Ac (IC50 = 8.5 muM). Furthermore, phyto C6 ceramide, D-erythro-dehydro C6 ceramide, and D-erythro-cis-C-6 ceramide had no effect on PP2Ac activity. Modification of the sphingoid chain also abolished the ability of ceramide to activate PP2Ac. Further studies demonstrated the requirement for the amide group, the primary hydroxyl group, and the secondary hydroxyl group of the sphingoid backbone for activation of PP2Ac through the synthesis and evaluation of D-erythro-urea C6 ceramide, L-erythro-urea C-6 ceramide, D-erythro-N-methyl C-6 ceramide, D-erythro-1-O-methyl C-6 ceramide, D-erythro-3-O-methyl C-6 ceramide, and (2S) 3-keto C-6 ceramide. None of these compounds induced significant activation of PP2Ac. Liposome binding studies were also conducted using analogs of D-erythro-C C6 ceramide, and the results showed that the ability of ceramide analogs to influence CAPP (activation or inhibition) was associated with the ability of the analogs to bind to CAPP. This study demonstrates strict structural requirements for interaction of ceramide with CAPP, and disclose ceramide as a very specific regulator of CAPP. The studies also begin to define features that transform ceramide analogs into inhibitors of CAPP.-Chalfant, C. E., Z. Szulc, P. Roddy, A. Bielawska, and Y. A. Hannun. The structural requirements for ceramide activation of serine-threonine protein phosphatases. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. RP Chalfant, CE (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM hannun@musc.edu FU NCI NIH HHS [CA-87584]; NIGMS NIH HHS [GM-19953-02] NR 45 TC 86 Z9 88 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2004 VL 45 IS 3 BP 496 EP 506 DI 10.1194/jlrM300347-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802VB UT WOS:000220189900011 PM 14657198 ER PT J AU Nestler, U Wakimoto, H Siller-Lopez, F Aguilar, LK Chakravarti, A Muzikansky, A Stemmer-Rachamimov, A Chiocca, EA Aguilar-Cordova, E Hochberg, FH AF Nestler, U Wakimoto, H Siller-Lopez, F Aguilar, LK Chakravarti, A Muzikansky, A Stemmer-Rachamimov, A Chiocca, EA Aguilar-Cordova, E Hochberg, FH TI The combination of adenoviral HSV TK gene therapy and radiation is effective in athymic mouse glioblastoma xenografts without increasing toxic side effects SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE ganciclovir; human glioblastoma; single dose radiation; spheroid ID MULTICELLULAR SPHEROIDS; IONIZING-RADIATION; BRAIN-TUMORS; COTTON RAT; IN-VIVO; GANCICLOVIR; NECROSIS; GROWTH; CANCER; VECTOR AB Object: In mouse models of prostate and breast cancer therapeutic effects are enhanced when adenoviral HSV TK gene therapy is combined with ionizing radiation. In the present study, we adopted this approach for the treatment of human glioblastoma xenografts in an athymic mouse model and assessed treatment results as well as toxic side effects. Methods: About 72 nude mice received intracerebral inoculations of 2 x 10(5) U87 DeltaEGFR cells. On day 7 after tumor implantation the study population was randomized into six treatment arms: (1) intratumoral buffer inoculation on day 7, (2) intratumoral adenoviral vector injection (2 x 10(9) vp) on day 7, (3) single dose radiation (2.1 Gy) on day 9, (4) adenoviral injection + radiation, (5) adenoviral injection + ganciclovir (GCV) (20 mug/g twice daily from day 8 to 17), (6) adenoviral injection + GCV + radiation. On day 21 half of the animals were sacrificed for histological evaluation of the brain tumors, the other half was assessed for survival. Results: This study showed significantly prolonged median survival time of 5 days for the GCV treated groups. The addition of radiation decreased the frequency of neurological symptoms and delayed the onset of deficits without altering the expression of thymidine kinase in the tumor cells. Conclusions: We conclude that adenoviral HSV TK gene therapy in combination with adjuvant radiotherapy does not generate increased toxic side effects in glioblastoma treatment. The prolonged survival time of animals receiving gene therapy and the reduced occurrence of neurological symptoms in irradiated mice constitute promising features of the combined treatment. C1 Massachusetts Gen Hosp E, Mol Neurooncol Lab, Charlestown, MA USA. Massachusetts Gen Hosp E, Dept Neurosurg, Charlestown, MA USA. Massachusetts Gen Hosp E, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp E, Dept Radiat Oncol, Charlestown, MA USA. Massachusetts Gen Hosp E, Neuropathol Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Gene Therapy Initiat, Boston, MA USA. Advantagene Inc, San Diego, CA USA. RP Nestler, U (reprint author), Univ Giessen, Dept Neurosurg, Klin Str 29, D-35385 Giessen, Germany. EM ulf.nestler@neuro.med.uni-giessen.de RI Nestler, Ulf/D-6503-2014; OI Nestler, Ulf/0000-0002-2963-4344; Siller-Lopez, Fernando/0000-0003-4542-4985 FU NCI NIH HHS [CA69246] NR 27 TC 17 Z9 18 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR-APR PY 2004 VL 67 IS 1-2 BP 177 EP 188 DI 10.1023/B:NEON.0000021897.53969.ca PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 806RX UT WOS:000220452100026 PM 15072465 ER PT J AU Wong, FCL Swartz, BE Gee, M Mandelkern, M AF Wong, FCL Swartz, BE Gee, M Mandelkern, M TI Occipital hypometabolism demonstrated by positron emission tomography after temporal lobectomy for refractory epilepsy SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID CROSSED CEREBELLAR DIASCHISIS; VISUAL-FIELD DEFICITS; LOBE EPILEPSY; ISCHEMIC LESIONS; BLOOD-FLOW; MEMORY; BRAIN; METABOLISM; RECOVERY; CORTEX AB Background: Epilepsy surgery involves well-planned discrete injury to the brain and may create visual deficits. This study seeks to evaluate the indirect effects of temporal lobectomy on brain metabolism by correlating visual field defects and glucose metabolism in the visual cortex of patients before and after undergoing epilepsy surgery. Methods: A retrospective survey of 11 patients who had undergone temporal lobectomy for refractory epilepsy in a single institution from 1986 to 1989, and who had prelobectomy and post-lobectomy visual field examinations and F-18 2-fluorodeoxyglucose positron emission tomography (FDG-PET) as part of a standard comprehensive epilepsy surgery evaluation. The PET images were analyzed to provide a correlation with the visual field defects that developed after the temporal lobectomy. Results: Occipital hypometabolism in the absence of structural lesions of the occipital lobe was noted in seven patients with contralateral visual field defects and in one of four patients without a visual field defect. FDG-PET studies in three patients repeated for as long as 20 months after lobectomy showed no significant change in the occipital hypometabolism pattern. Conclusions: Although the occipital cortex was not directly injured during temporal lobectomy, the resulting hypometabolism correlates with the clinical findings of visual field defects. The hypometabolism may be due to deafferentation after interruption of the optic pathways and appears to be persistent. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. W Los Angeles VAMC, Neurol Serv, Los Angeles, CA USA. W Los Angeles VAMC, PET Ctr, Los Angeles, CA USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Wong, FCL (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 59, Houston, TX 77030 USA. EM Fwong@di.mdacc.tmc.edu NR 28 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2004 VL 24 IS 1 BP 19 EP 23 DI 10.1097/00041327-200403000-00004 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 805BJ UT WOS:000220341500004 PM 15206433 ER PT J AU Fisher, CM AF Fisher, CM TI Neuroanatomic evidence to explain why bilateral internuclear ophthalmoplegia may result from occlusion of a unilateral pontine branch artery SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article AB Microscopic study of serial sections of the pons in two autopsy cases without known neurologic disease showed that the terminal portion of paramedian tegmental pontine arteries may divide to supply the region of the medial longitudinal fasciculus bilaterally. This finding provides the basis for the occurrence of bilateral internuclear ophthalmoplegia with unilateral basilar branch artery occlusion. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St, Boston, MA 02114 USA. NR 1 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD MAR PY 2004 VL 24 IS 1 BP 39 EP 41 DI 10.1097/00041327-200403000-00009 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 805BJ UT WOS:000220341500009 PM 15206438 ER PT J AU Rigalleau, F Caplan, D AF Rigalleau, F Caplan, D TI A deficit of automatic pronominal coindexation in aphasic patients SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE naming latency; pronouns; automatic coindexation process; aphasia ID BROCAS APHASICS; COMPREHENSION; SENSITIVITY; DISCOURSE; TIME; TASK AB The naming latency of a pronoun ('he' or 'she') was measured when a single previously presented name in the discourse agreed or did not agree with the pronoun. An effect of disagreement was found under conditions where participants had to judge whether the sentences were correct: pronouns that disagreed with previous names had longer naming latencies (Experiment 1). This effect was observed both in normal subjects and in aphasic patients, suggesting a preservation of the ability to immediately process a pronoun in these patients. For normal subjects, the disagreement effect was reduced but still significant when the judgement requirement was removed from the task. On the other hand, this effect was not present for aphasic patients under these conditions, suggesting a deficit of an automatic coindexation process (Experiment 3). Experiment 2 examined the effect of the number of potential antecedents on the immediate naming latency of a pronoun. The results of the three experiments are consistent with theories that assume a preservation of grammatical knowledge in aphasia despite a deficit of the on-line morphosyntactic processing of grammatical words. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Poitiers, CNRS UMR 6096, MSHS, Lab Langage & Cognit, F-86022 Poitiers, France. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Rigalleau, F (reprint author), Univ Poitiers, CNRS UMR 6096, MSHS, Lab Langage & Cognit, 99 Ave Recteur Pineau, F-86022 Poitiers, France. EM frigalleau@compuserve.com NR 35 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD MAR-MAY PY 2004 VL 17 IS 2-3 BP 181 EP 213 DI 10.1016/S0911-6044(03)00060-5 PG 33 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 802MO UT WOS:000220167800005 ER PT J AU Talavage, TM Sereno, MI Melcher, JR Ledden, PJ Rosen, BR Dale, AM AF Talavage, TM Sereno, MI Melcher, JR Ledden, PJ Rosen, BR Dale, AM TI Tonotopic organization in human auditory cortex revealed by progressions of frequency sensitivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SURFACE-BASED ANALYSIS; HUMAN-BRAIN; FUNCTIONAL-ORGANIZATION; ARCHITECTONIC FIELDS; SENSORY STIMULATION; ASSOCIATION CORTEX; MAGNETIC-FIELDS; CORTICAL FIELDS; MACAQUE MONKEYS; ACOUSTIC NOISE AB Functional neuroimaging experiments have revealed an organization of frequency-dependent responses in human auditory cortex suggestive of multiple tonotopically organized areas. Numerous studies have sampled cortical responses to isolated narrow-band stimuli, revealing multiple locations in auditory cortex at which the position of response varies systematically with frequency content. Because appropriate anatomical or functional grouping of these distinct frequency-dependent responses is uncertain, the number and location of tonotopic mappings within human auditory cortex remains unclear. Further, sampling does not address whether the observed mappings exhibit continuity as a function of position. This functional magnetic resonance imaging study used frequency-swept stimuli to identify progressions of frequency sensitivity across the cortical surface. The center-frequency of narrow-band, amplitude-modulated noise was slowly swept between 125 and 8,000 Hz. The latency of response relative to sweep onset was determined for each cortical surface location. Because frequency varied systematically with time, response latency indicated the frequency to which a location was maximally sensitive. Areas of cortex exhibiting a progressive change in response latency with position were considered tonotopically organized. There exist two main findings. First, six progressions of frequency sensitivity (i.e., tonotopic mappings) were repeatably observed in the superior temporal plane. Second, the locations of the higher- and lower-frequency endpoints of these progressions were approximately congruent with regions reported to be most responsive to discrete higher- and lower-frequency stimuli. Based on these findings and previous anatomical work, we propose a correspondence between these progressions and anatomically defined cortical areas, suggesting that five areas in human auditory cortex exhibit at least six tonotopic organizations. C1 Purdue Univ, W Lafayette, IN 47907 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Talavage, TM (reprint author), Purdue Univ, 465 Northwestern Ave, W Lafayette, IN 47907 USA. EM tmt@ecn.purdue.edu RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 FU NIDCD NIH HHS [P01DC-00119, T32 DC000038-12, T32DC-00038-04, P01 DC000119-24] NR 58 TC 145 Z9 146 U1 1 U2 16 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR 1 PY 2004 VL 91 IS 3 BP 1282 EP 1296 DI 10.1152/jn.01125.2002 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 774VG UT WOS:000189005800017 PM 14614108 ER PT J AU Huang, GD Feuerstein, M AF Huang, GD Feuerstein, M TI Identifying work organization targets for a work-related musculoskeletal symptom prevention program SO JOURNAL OF OCCUPATIONAL REHABILITATION LA English DT Article DE job stress; work organization; ergonomics; low back pain; upper extremity; symptoms; intervention ID UPPER EXTREMITY DISORDERS; CARPAL-TUNNEL-SYNDROME; FORM HEALTH SURVEY; RISK-FACTORS; PSYCHOSOCIAL FACTORS; OCCUPATIONAL STRESS; LIMB DISORDERS; BACK DISORDERS; PAIN; ENVIRONMENT AB While research linking work organization factors to work-related musculoskeletal disorders has been increasing, there is still a need to delineate specific dimensions to be targeted by intervention programs. The present cross-sectional investigation identified work organization risk factors for low back (LB) and upper extremity (UE) symptoms and determined the magnitudes of such associations. Questionnaires containing items on ergonomic, individual psychosocial, and occupational psychosocial factors were administered to a sample of workers (n = 248 U. S. Marines) in previously identified high-risk job categories for musculoskeletal disorders. Study participants were categorized into groups of either having LB symptoms only, UE symptoms only, concurrent LB and UE symptoms, or being asymptomatic on the basis of self-report. Additionally, measures of pain intensity, physical function, and mental health were obtained. Linear regression analyses adjusting for demographics, ergonomic factors, and individual psychosocial factors indicated that decision authority and experienced responsibility for work were significant correlates for pain intensity during the week. Logistic regression analyses indicated that ergonomic stressors were a risk factor for all symptomatic groups (OR = 1.02 per point increase; 95% CI: 1.0-1.1). Time pressure (OR = 1.2 per point increase; 95% CI: 1.0-1.4) was also a significant risk factor for all symptomatic groups, while cognitive processing placed workers at higher risks for concurrent LB and UE symptoms (OR = 1.2; 95% CI: 1.0-1.4). Interpersonal demands placed individuals at a lower risk for LB symptoms (OR = 0.8; 95% CI: 0.5-1.0). Findings highlight the importance of intervention approaches that address time pressure, cognitive processing factors, and interpersonal demands at work. In light of past biobehavioral studies, these results also suggest that job redesign and interventions that address a worker's workstyle when faced with increased work demands may help reduce the likelihood of musculoskeletal symptoms and/or their intensity. C1 Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. US Dept Vet Affairs, Off Res & Dev, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. Georgetown Univ, Sch Med, Dept Psychiat, Div Behav Med, Washington, DC USA. RP Feuerstein, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM mfeuerstein@usuhs.mil NR 64 TC 16 Z9 17 U1 4 U2 9 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1053-0487 J9 J OCCUP REHABIL JI J. Occup. Rehabil. PD MAR PY 2004 VL 14 IS 1 BP 13 EP 30 DI 10.1023/B:JOOR.0000015008.25177.8b PG 18 WC Rehabilitation; Social Issues SC Rehabilitation; Social Issues GA 771DP UT WOS:000188770600002 PM 15055501 ER PT J AU Troulis, MJ Williams, WB Kaban, LB AF Troulis, MJ Williams, WB Kaban, LB TI Staged protocol for resection, skeletal reconstruction, and oral rehabilitation of children with jaw tumors SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT Meeting of the International-Association-for-Dental-Research/American-Association-for-D ental-Research CY MAR 06-09, 2002 CL SAN DIEGO, CA SP Int Assoc Dent Res, Amer Assoc Dent Res ID MANDIBULAR RECONSTRUCTION; OSSEOINTEGRATED IMPLANTS; BONE-GRAFTS; MAXILLOFACIAL TUMORS; IMMEDIATE; DEFECTS; ADOLESCENTS; EXPERIENCE; PLATES; CONTINUITY AB Purpose: The purpose of this study was to evaluate a staged protocol for resection of jaw tumors and reconstruction including implants in pediatric patients. Patients and Methods: Nine children were evaluated retrospectively. Data included age at resection, tumor type, use of adjuvant therapy, type of bone graft, and number of implants. Occurrence of postoperative infection, tumor margins, recurrence, plate fractures, number of bone grafts, implants restored, and failures were recorded. Results: Ages ranged from 3.5 to 16 years with 2 maxillary and 7 mandibular tumors. Diagnoses included giant cell lesion (n = 3), osteosarcoma (n = 2), myofibroma (n = 1), ossifying fibroma (n = 1), desmoplastic fibroma (n = 1), and ameloblastoma (n = 1). No patients experienced postoperative infection, wound dehiscence, or jaw instability after en bloc resection. One patient had recurrence of a giant cell lesion. To date (mean, 56 months; range, 24 to 93 months), there have been no additional recurrences. There was 1 plate fracture. Eight patients underwent iliac bone grafts (stage 2), and in I patient, the mandible regenerated. There were no graft infections or wound dehiscences. Three patients required additional bone grafting for implant placement. Twenty-three implants were placed in 7 patients without complications, and 21 implants have gone to second stage. One implant failed to osseointegrate. Six patients have had prostheses placed and loaded for a mean of 26 months (range, 5 to 64 months). one patient is scheduled for prosthetic restoration and 2 for implant placement. Conclusion: Pediatric maxillofacial tumors can be successfully treated by resection, rigid fixation, and delayed reconstruction with minimal morbidity and a high success rate. (C) 2004 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM mtroulis@partners.org FU NIDCR NIH HHS [K23 DE14070-01] NR 40 TC 28 Z9 29 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2004 VL 62 IS 3 BP 335 EP 343 DI 10.1016/j.joms.2003.07.006 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 800SG UT WOS:000220047400013 PM 15015167 ER PT J AU Li, G Zayontz, S Most, E DeFrate, LE Suggs, JF Rubash, HE AF Li, G Zayontz, S Most, E DeFrate, LE Suggs, JF Rubash, HE TI In situ forces of the anterior and posterior cruciate ligaments in high knee flexion: an in vitro investigation SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE knee biomechanics; high flexion; anterior cruciate ligament; posterior cruciate ligament; kinetics ID BIOMECHANICAL ANALYSIS; TIBIAL LOADS; MUSCLE LOADS; KINEMATICS; JOINT; RECONSTRUCTION; CONSEQUENCES; DEFICIENCY; BUNDLES; MOTION AB The function of the anterior and posterior cruciate ligaments (ACL and PCL) in the first 120degrees of flexion has been reported extensively. but little is known of their behavior at higher flexion angles. The aim of this investigation was to study the effects of muscle loads on the in situ forces in both ligaments at high knee flexion (> 120degrees). Eighteen fresh-frozen human knee specimens were tested on a robotic testing system from full extension to 150degrees of flexion in response to quadriceps (400 N), hamstrings (200 N), and combined quadriceps and hamstrings (400 N/200 N) loads. The in situ forces in the ACL and PCL were measured using the principle of superposition. The force in the ACL peaked at 30degrees of flexion (71.7 +/- 27.9 N in response to the quadriceps load, 52.3 +/- 24.4 N in response to the combined muscle load, 32.3 +/- 20.9 N in response to the hamstrings load). At 150degrees, the ACL force was approximately 30 N in response to the quadriceps load and 20 N in response to the combined muscle load and isolated hamstring load. The PCL force peaked at 90degrees (34.0 +/- 15.3 N in response to the quadriceps load, 88.6 +/- 23.7 N in response to the combined muscle load, 99.8 +/- 24.0 N in response to the hamstrings load) and decreased to around 35 N at 150degrees in response to each of the loads. These results demonstrate that the ACL and PCL carried significantly less load at high flexion in response to the simulated muscle loads compared to the peak loads they carried in response to the same muscle loads at other flexion angles. The data could provide a reference point for the investigation of non-weight bearing flexion and extension knee exercises in high flexion. Furthermore, these data could be useful in designing total knee implants to achieve high flexion. (C) 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Orthopaed Biomech L, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Orthopaed Biomech L, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 25 TC 54 Z9 60 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2004 VL 22 IS 2 BP 293 EP 297 DI 10.1016/S0736-0266(03)00179-7 PG 5 WC Orthopedics SC Orthopedics GA 800KS UT WOS:000220027800009 PM 15013087 ER PT J AU Tan, G Jensen, MP Thornby, JI Shanti, BF AF Tan, G Jensen, MP Thornby, JI Shanti, BF TI Validation of the brief pain inventory for chronic nonmalignant pain SO JOURNAL OF PAIN LA English DT Article DE pain assessment instrument; chronic nonmalignant pain ID LOW-BACK-PAIN; CANCER PAIN; CEREBRAL-PALSY; VERSION; INTERFERENCE; ADJUSTMENT; SEVERITY; VALIDITY; UTILITY AB The Brief Pain Inventory (BPI; Cleeland and associates) has been used primarily to assess patients with cancer-related pain. Although it has been validated in many languages and is widely used, there has not yet been research published to validate its use for patients with chronic nonmalignant pain as the primary presenting problem. This study was designed to fill this gap by examining the psychometric properties of the BPI in 440 patients with chronic intractable pain referred to a chronic pain clinic at a metropolitan tertiary-care teaching hospital. Results indicated acceptable internal consistency (Cronbach alpha coefficients were .85 for the intensity items and .88 for the interference items). A factor analysis resulted in 2 distinct and independent factors, supporting the validity of the 2-factor structure of the BPI. Zero-order correlations indicated that the association with a measure of disability (the Roland-Morris Disability Questionnaire [RMDQ]) was significantly higher for BPI interference (r = 0.57) than for BPI intensity (r = 0.40, t = 5.71, P < .01) and that the correlation with BPI interference was not more than 0.80, supporting the conclusion that these scales assess related, but also distinct, dimensions. Finally, the finding that both BPI scales showed statistically significant improvement with treatment confirms the responsivity of BPI in detecting and reflecting improvement in pain over time. Perspective: This paper validated the psychometric properties of a pain Assessment instrument (The Brief Pain inventory) originally developed to assess cancer pain and extended its use for the chronic nonmalignant pain population. This provides an important and widely used diagnostic tool for the clinician treating chronic pain. (C) 2004 by the American Pain Society. C1 Anesthesiol & Mental Hlth Care Line Subst Depende, Pain Sect, Houston, TX USA. Houston VA Med Ctr, Pain Sect, Houston, TX USA. Baylor Coll Med, Vet Affairs Med Ctr, Dept Anesthesiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Family Med, Houston, TX 77030 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Tan, G (reprint author), Baylor Coll Med, Vet Affairs Med Ctr, Dept Anesthesiol, 2002 Holcombe Blvd,116 MH C-L, Houston, TX 77030 USA. EM tan.gabriel@med.va.gov NR 31 TC 410 Z9 417 U1 3 U2 23 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD MAR PY 2004 VL 5 IS 2 BP 133 EP 137 DI 10.1016/j.jpain.2003.12.005 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 811KP UT WOS:000220771100008 PM 15042521 ER PT J AU Weisbord, SD Fried, LF Arnold, RM Rotondi, AJ Fine, MJ Levenson, DJ Switzer, GE AF Weisbord, SD Fried, LF Arnold, RM Rotondi, AJ Fine, MJ Levenson, DJ Switzer, GE TI Development of a symptom assessment instrument for chronic hemodialysis patients: The dialysis symptom index SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE symptom burden; hemodialysis; scale development ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; CANCER PAIN MANAGEMENT; PHYSICAL SYMPTOMS; PALLIATIVE CARE; PSYCHOSOCIAL FACTORS; MEDICAL-CENTER; PREVALENCE; OUTCOMES; RATINGS AB Little is known about the prevalence, severity, or impact of symptoms in hemodialysis patients because of the lack of a validated symptom assessment instrument. We systematically developed an index to assess physical and emotional symptom burden in this patient population. We employed four steps in the generation of this index: a review of dialysis quality-of-life instruments, three focus groups, experts' content validity assessment, and test-retest reliability measurement. Seventy-five symptoms were identified. Of these, 46 appeared in greater than or equal to 4 of the instruments/focus groups and were considered for inclusion. Twelve were grouped into other symptom constructs and experts judged four of the remaining items not to be pertinent, leaving 30 items in the new index. Overall kappa statistic was 0.48 +/- 0.22. These steps allowed the systematic development of a 30-item symptom assessment index for hemodialysis patients. Additional reliability and validity testing is needed prior to its widespread use. (C) 2004 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Inst Performance Improvement, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Ctr Bioeth & Hlth Law, Pittsburgh, PA USA. Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), Univ Pittsburgh, Med Ctr, Renal Electrolyte Div, A919 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NHLBI NIH HHS [T32 HL 07820-05] NR 55 TC 66 Z9 72 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2004 VL 27 IS 3 BP 226 EP 240 DI 10.1016/j.jpainsymman.2003.07.004 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 806OV UT WOS:000220444100006 PM 15010101 ER PT J AU Gapski, R Barr, JL Sarment, DP Layher, MG Socransky, SS Giannobile, WV AF Gapski, R Barr, JL Sarment, DP Layher, MG Socransky, SS Giannobile, WV TI Effect of systemic matrix metalloproteinase inhibition on periodontal wound repair: A proof of concept trial SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE bone resorption/prevention and control; doxycycline/therapeutic use; periodontal attachment; periodontal diseases/therapy; surgical flaps ID SUBANTIMICROBIAL DOSE DOXYCYCLINE; LIGATURE-INDUCED PERIODONTITIS; FLUID COLLAGENASE ACTIVITY; GINGIVAL CREVICULAR FLUID; REPOSITIONED FLAP SURGERY; ADULT PERIODONTITIS; SUBGINGIVAL MICROFLORA; BONE-RESORPTION; CARBOXYTERMINAL TELOPEPTIDE; MACACA-FASCICULARIS AB Background: The adjunctive use of matrix metal loproteinase (MMP) inhibitors with scaling and root planing (SRP) promotes new attachment in patients with periodontal disease. This pilot study was designed to examine aspects of the biological response brought about by the MMP inhibitor low dose doxycycline (LDD) combined with access flap surgery (AFS) on the modulation of periodontal wound repair in patients with severe chronic periodontitis. Methods: Twenty-four subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate clinical, biochemical, and microbial measures of disease in response to 6 months therapy of either placebo capsules + AFS or LDD (20 mg b.i.d.) + AFS. Clinical measures including probing depth (PD), clinical attachment levels (CAL), and bleeding on probing (BOP) as well as gingival crevicular fluid bone marker assessment (ICTP) and microbial DNA analysis (levels and proportions of 40 bacterial species) were performed at baseline and 3, 6, 9, and 12 months. Results: Patients treated with LDD + AFS showed more potent reductions in PD in surgically treated sites of > 6 mm (P < 0.05, 12 months). Furthermore, LDD + AFS resulted in greater reductions in ICTP levels compared to placebo + AFS. Rebounds in ICTP levels were noted when the drug was withdrawn. No statistical differences between the groups in mean counts were found for any pathogen tested. Conclusions: This pilot study suggests that LDD in combination with AFS may improve the response of surgical therapy in reducing probing depth in severe chronic periodontal disease. LDD administration also tends to reduce local periodontal bone resorption during drug administration. The use of LDD did not appear to contribute to any significant shifts in the microbiota beyond that of surgery alone. C1 Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Dent, Ctr Craniofacial Regenerat, Ann Arbor, MI USA. Forsyth Inst, Boston, MA USA. Univ Michigan, Coll Engn, Dept Bioengn, Ann Arbor, MI 48109 USA. RP Giannobile, WV (reprint author), Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, 1011 N Univ Ave,Room 3397, Ann Arbor, MI 48109 USA. EM wgiannob@umich.edu OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [DE12861, T35 DE007101, R37 DE010977-06, DE10977, T35 DE007101-22, 5T35 DE07101, P01 DE012861, P01 DE012861-01, R37 DE010977] NR 60 TC 33 Z9 34 U1 0 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAR PY 2004 VL 75 IS 3 BP 441 EP 452 DI 10.1902/jop.2004.75.3.441 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 806WX UT WOS:000220465100014 PM 15088883 ER PT J AU Goodson, JM AF Goodson, JM TI Confusion between definitive and exploratory clinical therapy trials: When to believe and when to question SO JOURNAL OF PERIODONTOLOGY LA English DT Editorial Material C1 Forsyth Inst, Boston, MA 02115 USA. RP Goodson, JM (reprint author), Forsyth Inst, 140 The Fenway, Boston, MA 02115 USA. EM MGoodson@forsyth.org NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAR PY 2004 VL 75 IS 3 BP 493 EP 494 DI 10.1902/jop.2004.75.3.493 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 806WX UT WOS:000220465100021 PM 15088890 ER PT J AU Buhlmann, U McNally, RJ Etcoff, NL Tuschen-Caffier, B Wilhelm, S AF Buhlmann, U McNally, RJ Etcoff, NL Tuschen-Caffier, B Wilhelm, S TI Emotion recognition deficits in body dysmorphic disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE emotion recognition; face recognition; Body Dysmorphic Disorder; Obsessive-Compulsive Disorder ID OBSESSIVE-COMPULSIVE DISORDER; FACIAL AFFECT; RATING-SCALE; SCHIZOPHRENIA; PERFORMANCE; RELIABILITY; VERSION AB Patients with Body Dysmorphic Disorder (BDD) are characterized by excessive concerns about imagined defects in their appearance, most commonly, facial features. In this study, we investigated (1) the ability to identify facial expressions of emotion, and (2) to discriminate single facial features in BDD patients, Obsessive-Compulsive Disorder (OCD) patients, and in healthy control participants. Specifically, their ability for general facial feature discrimination was assessed using the Short Form of the Benton Facial Recognition Test (Benton AL, Hamsher KdeS, Varney NR, Spreen O. Contributions to neuropsychological assessment: a clinical manual. New York: Oxford University Press; 1983). However, findings of the BFRT indicate no differences among the groups. Moreover, participants were presented with facial photographs from the Ekman and Friesen (Ekman P, Friesen W. Unmasking the face: a guide to recognizing emotions from facial cues. Englewood Cliffs, NJ: Prentice-Hall; 1975 and Ekman P, Friesen W. Pictures of facial affect. Palo Alto: Consulting Psychologists Press, 1976) series and were asked to identify the corresponding emotion. The BDD group was less accurate than the control group, but not the OCD group, in identifying facial expressions of emotion. Relative to the control and OCD groups, the BDD group more often misidentified emotional expressions as angry. In contrast to the findings of Sprengelmeyer et al. [Proc. Royal Soc. London Series B: Biol. Sci. 264 (1997),1767], OCD patients did not show a disgust recognition deficit. Poor insight and ideas of reference, common in BDD, might partly result from an emotion recognition bias for angry expressions. Perceiving others as angry and rejecting might reinforce concerns about one's personal ugliness and social desirability. (C) 2003 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, OCD Clin, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02129 USA. Univ Gesamthsch Siegen, Dept Psychol, D-57068 Siegen, Germany. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, OCD Clin, 13th St, Charlestown, MA 02129 USA. EM wilhelm@psych.mgh.harvard.edu NR 27 TC 69 Z9 70 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAR-APR PY 2004 VL 38 IS 2 BP 201 EP 206 DI 10.1016/S0022-3956(03)00107-9 PG 6 WC Psychiatry SC Psychiatry GA 775WP UT WOS:000189083900012 PM 14757335 ER PT J AU Hinton, D So, V Pollack, MH Pitman, RK Orr, SP AF Hinton, D So, V Pollack, MH Pitman, RK Orr, SP TI The psychophysiology of orthostatic panic in Cambodian refugees attending a psychiatric clinic SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE hypotension; orthostatic; catastrophic cognitions; stress disorders; posttraumatic; panic disorder; refugee ID POSTTRAUMATIC-STRESS-DISORDER; HEART-RATE-VARIABILITY; BLOOD-PRESSURE; CARDIOVASCULAR ACTIVITY; AUTONOMIC REGULATION; MAJOR DEPRESSION; MASS VIOLENCE; ANXIETY; TRAUMA; CHALLENGE AB Orthostatically triggered panic was examined in female Cambodian refugees. Heart rate, blood pressure ( BP), panic, and dizziness responses were assessed during orthostatic challenge in three diagnostic groups: orthostatic panic without comorbid posttraumatic stress disorder ( PTSD), orthostatic panic with PTSD, and other mental disorders without orthostatic panic or PTSD. During orthostatic challenge, the panic group without PTSD showed a significant drop, whereas the group with other mental disorders showed an increase in systolic BP. The group with panic and PTSD showed a blunted systolic BP response during orthostasis that fell between the responses of the other groups. Catastrophic, culturally specific cognitions present during orthostatic challenge were significantly correlated with the amount of reported panic upon standing. Some patients recalled previous traumatic events during the orthostatic challenge. The findings suggest that orthostatically induced panic attacks in Cambodian refugees are generated by an interaction of orthostasis physiology, catastrophic cognitions, and trauma associations. C1 Arbour Counseling Serv, Lowell, MA 01852 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. N Suffolk Mental Hlth Ctr, SE Asian Clin, Revere, MA USA. Vet Affairs Med Ctr, Manchester, NH USA. RP Hinton, D (reprint author), Arbour Counseling Serv, 10 Bridge St,Simpson Block, Lowell, MA 01852 USA. NR 72 TC 23 Z9 24 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2004 VL 26 IS 1 BP 1 EP 13 DI 10.1023/B:JOBA.0000007451.85942.42 PG 13 WC Psychology, Clinical SC Psychology GA 752EC UT WOS:000187133200001 ER PT J AU Tolin, DF Maltby, N Weathers, FW Litz, BT Knight, J Keane, TM AF Tolin, DF Maltby, N Weathers, FW Litz, BT Knight, J Keane, TM TI The use of the MMPI-2 infrequency-psychopathology scale in the assessment of posttraumatic stress disorder in male veterans SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV, 1997 CL MONTREAL, CANADA SP Int Soc Traumat Stress Studies DE MMPI-2; Fp; posttraumatic stress disorder; symptom overreporting ID COMPENSATION SEEKING STATUS; VIETNAM COMBAT VETERANS; PTSD; SYMPTOMS; F(P); VALIDATION AB This study evaluated the use of the FP (Infrequency - Psychopathology) scale of the Minnesota Multiphasic Personality Inventory - 2 (MMPI-2) as a measure of symptom overreporting among 423 service-seeking male veterans with and without PTSD. Results were consistent with several predictions based on the logic of the F-P scale. F-P produced lower scores for PTSD and non-PTSD patients than the other two MMPI-2 measures of infrequent responding; F and F-B. F-P also resulted in fewer invalid protocols than did F or F-B. Finally, F-P yielded lower correlations with MMPI-2 and other measures of psychopathology than did F or F-B. Consistent with previous studies, compensation-seeking status was associated with extreme elevations across clinical and validity scales. Contrary to previous findings, however, compensation-seeking veterans were also more likely to receive a PTSD diagnosis. Implications for the relationship between compensation seeking and symptom overreporting are discussed. C1 Inst Living, Anxiety Disorder Ctr, Hartford, CT 06106 USA. Auburn Univ, Auburn, AL 36849 USA. Boston Univ, Sch Med, Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Tolin, DF (reprint author), Inst Living, Anxiety Disorder Ctr, 200 Retreat Ave, Hartford, CT 06106 USA. NR 26 TC 2 Z9 2 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD MAR PY 2004 VL 26 IS 1 BP 23 EP 29 DI 10.1023/B:JOBA.0000007453.24885.39 PG 7 WC Psychology, Clinical SC Psychology GA 752EC UT WOS:000187133200003 ER PT J AU Montezuma, SR Rizzo, JF Ziv, OR AF Montezuma, SR Rizzo, JF Ziv, OR TI Differential recovery of the electroretinogram, visually evoked cortical potential, and electrically evoked cortical potential following vitrectomy: Implications for acute testing of an implanted retinal prosthesis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE electrically evoked cortical potential (EECP); electroretinogram (ERG); retinal prosthesis; visually evoked cortical potential (VECP); vitrectomy ID INTRAOCULAR-PRESSURE; IRRIGATING SOLUTIONS; LOCAL HYPOTHERMIA; STIMULATION; RABBIT; SURGERY; MICROELECTRODE; TEMPERATURE; THRESHOLDS; RESPONSES AB To determine the extent to which electrophysiologic tests of the afferent visual pathway are affected by vitrectomy, the procedure was performed in 15 eyes of I I adult Dutch-belted rabbits. An electroretinogram (ERG), visually evoked cortical potential (VECP), and electrically evoked cortical potential (EECP) were obtained preoperatively and sequentially after surgery. For electrical stimulations, biphasic impulses were delivered to the retina. Post-vitrectomy declines of 49, 25, and 41% from the median baseline amplitudes and increases of 13, 18, and 17% from the median baseline latency values were found for ERG VECP, and EECP, respectively. At 90 min, 13 to 30% of eyes still had an amplitude more than 10% below baseline on at least one of the three tests, whereas 10 to 47% of eyes had an abnormal latency more than 10% above baseline on at least one of the three tests. Amplitudes were more likely than latencies to return to near baseline, but for eyes that remained subnormal, the decline was greater for amplitudes than latencies. Significant alterations in retinal function, manifested by declines in amplitudes and increases in latencies of the ERG, VECP, and EECP, persist in a large proportion of eyes up to 90 min post-vitrectomy. C1 Vet Affairs Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RP Rizzo, JF (reprint author), Vet Affairs Med Ctr, Ctr Innovat Visual Rehabil, 151 S Huntington Ave, Boston, MA 02130 USA. EM joseph.rizzo@med.va.gov NR 41 TC 5 Z9 5 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2004 VL 41 IS 2 BP 113 EP 120 DI 10.1682/JRRD.2004.02.0113 PG 8 WC Rehabilitation SC Rehabilitation GA 826CW UT WOS:000221807600005 PM 15558366 ER PT J AU Stelmack, J Szlyk, JP Stelmack, T Babcock-Parziale, J Demers-Turco, P Williams, RT Massof, RW AF Stelmack, J Szlyk, JP Stelmack, T Babcock-Parziale, J Demers-Turco, P Williams, RT Massof, RW TI Use of Rasch person-item map in exploratory data analysis: A clinical perspective\ SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE low-vision; outcomes measurement; Rasch analysis; rehabilitation ID LOW-VISION REHABILITATION; RETINITIS-PIGMENTOSA; FUNCTIONAL STATUS; VISUAL FUNCTION; SYSTEMS-MODEL; DIFFICULTY; OUTCOMES AB The National Institutes of Health (NIH) includes visual impairment in the 10 most prevalent causes of disability in America. As rehabilitation programs have the potential to restore independence and improve the quality of life for affected persons, NIH research priorities include evaluating their effectiveness. This paper demonstrates a clinical perspective on the use of the Rasch person-item map to evaluate the range and precision of a new vision function questionnaire in early analysis (prior to full sample). A self-report questionnaire was developed to measure the difficulty that persons with different levels of vision loss have performing daily activities. This 48-item Veterans Affairs Low-Vision Visual Functioning Questionnaire (VA LV VFQ-48) was administered to 117 low-vision patients. Preliminary analysis indicates that the questionnaire items are applicable to persons of differing abilities. The Rasch person-item map demonstrates that the field-test version of the VA LV VFQ-48 has good range and is well centered with respect to the person measure distribution. Construct validity and reliability are also demonstrated. C1 Edward Hines Jr Vet Adm Hosp, Blind Rehabil Ctr 124, Hines, IL 60141 USA. Illinois Coll Optometry, Chicago, IL USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL USA. VA Chicago Hlth Care Syst, W Side Div, Chicago, IL USA. So Arizona VA Healthcare Syst, SW Blind Rehabil Ctr, Tucson, AZ USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Harvard Univ, Sch Med, Dept Ophthalmol,Lois & Edwin Deicke Ctr Vis Rehab, Vis Rehabil Ctr,Massachusetts Eye & Ear Infirm, Boston, MA USA. Loyola Univ, Sch Med, Maywood, IL 60153 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Lions Vis Res & Rehabil Ctr, Baltimore, MD USA. RP Stelmack, J (reprint author), Edward Hines Jr Vet Adm Hosp, Blind Rehabil Ctr 124, Hines, IL 60141 USA. EM Joan.Stelmack@med.va.gov NR 27 TC 34 Z9 36 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2004 VL 41 IS 2 BP 233 EP 241 DI 10.1682/JRRD.2004.02.0233 PG 9 WC Rehabilitation SC Rehabilitation GA 826CW UT WOS:000221807600016 PM 15558377 ER PT J AU Starkebaum, G Sasso, EH AF Starkebaum, G Sasso, EH TI Hepatitis C and B cells: Induction of autoimmunity and lymphoproliferation may reflect chronic stimulation through cell-surface receptors SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID VIRUS-INFECTION; SJOGRENS-SYNDROME; LYMPHOMA; GENE; CRYOGLOBULINEMIA; PROTEIN; COMPLEX C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Rheumatol, Seattle, WA 98195 USA. RP Starkebaum, G (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, S-01 COS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Gordon.Starkebaum@med.va.gov NR 24 TC 12 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2004 VL 31 IS 3 BP 416 EP 418 PG 3 WC Rheumatology SC Rheumatology GA 802FF UT WOS:000220148700004 PM 14994381 ER PT J AU Mair, SD Viola, RW Gill, TJ Briggs, KK Hawkins, RJ AF Mair, SD Viola, RW Gill, TJ Briggs, KK Hawkins, RJ TI Can the impingement test predict outcome after arthroscopic subacromial decompression? SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID ROTATOR CUFF; ACROMIOPLASTY; SHOULDER; LESIONS AB The impingement test, placement of local anesthetic in the subacromial space, is considered a useful tool in diagnosing impingement syndrome. The purpose of this study was to examine the predictive value of the impingement test with respect to outcome after arthroscopic subacromial decompression. Fifty-five patients who had a preoperative impingement test were evaluated at 3 and 12 months postoperatively. We noted 88% satisfactory results in patients in whom the impingement test was positive, with only 63% satisfactory results at 3 months and 60% satisfactory results at 12 months in patients in whom the impingement test was negative. Although workers' compensation patients tended to have lower scores than others, the impingement test result was more predictive of outcome than was compensation status. Impingement test results and preoperative American Shoulder and Elbow surgeons scores were independent predictors of postoperative American Shoulder and Elbow Surgeons scores. Our evidence indicates that the impingement test can be used as a predictor of outcome for patients with impingement syndrome treated by arthroscopic subacromial decompression. C1 Steadman Hawkins Sports Med Fdn, Clin Res, Vail, CO 81657 USA. Univ Kentucky, Sect Sports Med, Lexington, KY USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Hawkins, RJ (reprint author), Steadman Hawkins Sports Med Fdn, Clin Res, 181 W Meadow Dr,Suite 1000, Vail, CO 81657 USA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2004 VL 13 IS 2 BP 150 EP 153 DI 10.1016/j.jse.2003.12.006 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 804AX UT WOS:000220272700005 PM 14997090 ER PT J AU Sloan, SM Budoff, JE Hipp, JA Nguyen, L AF Sloan, SM Budoff, JE Hipp, JA Nguyen, L TI Coracoclavicular ligament reconstruction using the lateral half of the conjoined tendon SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID ROTATOR CUFF TEARS; ACROMIOCLAVICULAR DISLOCATIONS; CORACOACROMIAL LIGAMENT; ASYMPTOMATIC SHOULDERS; GLENOHUMERAL JOINT; REPAIR; DEBRIDEMENT; REPLACEMENT; INJURIES; COMPLEX AB To preserve the corocoacromial (CA) ligament, we have used the lateral half of the conjoined tendon as an outograft source to replace the coracoclavicular (CC) ligament. The purpose of this study is to compare the ultimate tensile strength of the lateral 12 mm of the conjoined tendon with that of the CA ligament and the CC ligament. Eight paired cadaveric male shoulders were tested to tensile failure with a custom pneumatic testing apparatus. Although the lateral 12 mm of the conjoined tendon was stronger than the CA ligament, this difference was not statistically significant (P = .37). However, the intact CC ligament (621 +/- 209 N) was approximately 250% stronger than either the lateral 12 mm of the conjoined tendon (265 +/- 79 N., P < .001) or the CA ligament (246 +/- 69 N, P < .001). We believe that the lateral half of the conjoined tendon is a viable alternative outograft source for reconstruction of the CC ligament in cases of symptomatic acromioclavicular joint dislocation. Though not as strong as the native CC ligaments, the conjoined tendon is slightly stronger than the commonly used CA ligament. C1 Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. RP Budoff, JE (reprint author), 6550 Fannin St,Suite 2525, Houston, TX 77030 USA. EM jbudoff@bcm.tmc.edu NR 36 TC 26 Z9 34 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2004 VL 13 IS 2 BP 186 EP 190 DI 10.1016/j.jse.2003.12.002 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 804AX UT WOS:000220272700012 PM 14997097 ER PT J AU Martin, A Bostic, JQ Pruett, K AF Martin, A Bostic, JQ Pruett, K TI The VIP.: Hazard and promise in treating "special" patients SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Yale Sch Med, New Haven, CT USA. Yale New Haven Childrens Hosp, Childrens Psychiat Inpatient Serv, New Haven, CT USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. RP Martin, A (reprint author), Yale Child Study Ctr, 230 S Frontage Rd, New Haven, CT 06520 USA. EM andres.martin@yale.edu NR 0 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2004 VL 43 IS 3 BP 366 EP 369 DI 10.1097/01.chi.0000106853.88132.81 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 776HJ UT WOS:000189110300018 PM 15076271 ER PT J AU Katz, KA Jonasch, E Hodi, FS Haluska, F AF Katz, KA Jonasch, E Hodi, FS Haluska, F TI Melanoma of unknown primary: Experience at the Dana Farber-Partners Cancer Center and review of the literature SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Academy-of-Dermatology CY FEB 06-11, 2004 CL WASHINGTON, DC SP Amer Acad Dermatol C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2004 VL 50 IS 3 SU S MA P24 BP P6 EP P6 DI 10.1016/j.jaad.2003.10.030 PG 1 WC Dermatology SC Dermatology GA 802CC UT WOS:000220140600025 ER PT J AU Royall, DR Palmer, R Chiodo, LK Polk, MJ AF Royall, DR Palmer, R Chiodo, LK Polk, MJ TI Declining executive control in normal aging predicts change in functional status: The freedom house study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aging; disability; assessment; longitudinal; executive function ID MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT; STRUCTURAL MODELS; ELDERLY RETIREES; DISABILITY; LEVEL; OLDER; POPULATION; INTERVIEW; FEATURES AB OBJECTIVES: To assess the contribution of executive control function (ECF) to functional status. DESIGN: Three-year longitudinal cohort study. SETTING: A comprehensive-care retirement community. PARTICIPANTS: Five hundred forty-seven noninstitutionalized septuagenarians. MEASUREMENTS: The Mini-Mental State Examination (MMSE) and Executive Interview (EXIT25). Functional status was assessed using instrumental activities of daily living (IADLs). Latent growth curves of MMSE, EXIT25, and IADL were modeled. The rate of change in IADLs (DeltaIADL), adjusted for baseline IADLs and cognition, was regressed on the rate of change in each cognitive measure (adjusted for baseline cognition). Models were also adjusted for baseline age, level of care, and comorbid illnesses. RESULTS: Baseline test scores were within normal ranges, but mean EXIT25 scores reached the impaired range by the second follow-up. There was significant variability around the baseline means and slopes for all variables. The rate of change in EXIT25 was strongly correlated with DeltaIADL (r=-0.57, P<.001). This remained significant after adjusting for baseline EXIT25 scores, IADLs, age, comorbid disease, and level of care. The effect of the EXIT25 on DeltaIADL was stronger than those of age, baseline IADLs, comorbid disease, or level of care. The rate of change in MMSE scores was not significantly associated with DeltaIADL. CONCLUSION: ECF is a significant and independent correlate of functional status in normal aging. Traditional dementia case finding is likely to underestimate cognition-related disability. Neither a normal baseline MMSE score nor stable MMSE scores over time preclude functionally significant changes in ECF. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Family Practice, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM royall@uthscsa.edu NR 44 TC 154 Z9 158 U1 1 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2004 VL 52 IS 3 BP 346 EP 352 DI 10.1111/j.1532-5415.2004.52104.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 774PA UT WOS:000188990600003 PM 14962147 ER PT J AU Rodrigues, ACT d'Avila, A Houghtaling, C Ruskin, JN Picard, M Reddy, VY AF Rodrigues, ACT d'Avila, A Houghtaling, C Ruskin, JN Picard, M Reddy, VY TI Intrapericardial echocardiography: A novel catheter-based approach to cardiac imaging SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID RECURRENT VENTRICULAR-TACHYCARDIA; INTRACARDIAC ECHOCARDIOGRAPHY; CREATION; ABLATION; LESIONS AB Background: Transvascular catheter-based intracardiac echocardiography has been successfully used to help guide catheter ablation and electrophysiologic procedures. it has recently been demonstrated that catheters can be safely placed into the pericardial space to allow for epicardial cardiac mapping and ablation. We evaluated the feasibility of catheter-based intrapericardial echocardiography (IPE) during such procedures to identify cardiac structures and visualize intracardiac catheters. Methods: IPE was performed in 7 goats by placing a phased-array ultrasound transducer contained within a 10F steerable catheter into the pericardial. space using the same transthoracic subxyphoid approach as used to map and ablate epicardial ventricular tachycardia. Images were obtained of cardiac structures and of intracardiac ablation catheters. After the procedure, the hearts were harvested to assess for possible IPE-related lesions. Results: The IPE catheter could be easily placed inside the pericardial space in all animals. In 7 of 7 cases, longitudinal and short-axis views of right- and left-sided chambers and valves were obtained, similar in orientation to transesophageal echocardiography. Visualization of atrial appendages (6/7), pulmonary veins (6/7), coronary arteries (6/7), and coronary sinus (3/6) was also feasible. Assessment of intracardiac transvalvar and venous blood flow was achieved by spectral and color Doppler. The ablation catheter could be clearly visualized inside cardiac chambers. No arrhythmias were induced with IPE catheter manipulation. After harvesting the hearts, no lesions resulting from the procedure were observed. Conclusion: In this experimental setting, IPE was able to provide detailed images of cardiac structures and establish the relative position of the ablation catheter. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Echocardiog Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010; OI d'Avila, Andre Luiz/0000-0001-8769-1411; Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [K23 HL 68064-01A1] NR 10 TC 8 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAR PY 2004 VL 17 IS 3 BP 269 EP 274 DI 10.1067/j.echo.2003.10.024 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 800TB UT WOS:000220049500013 PM 14981426 ER PT J AU Thongboonkerd, V Barati, MT McLeish, KR Benarafa, C Remold-O'Donnell, E Zheng, SR Rovin, BH Pierce, WM Epstein, PN Klein, JB AF Thongboonkerd, V Barati, MT McLeish, KR Benarafa, C Remold-O'Donnell, E Zheng, SR Rovin, BH Pierce, WM Epstein, PN Klein, JB TI Alterations in the renal elastin-elastase system in type 1 diabetic nephropathy identified by proteomic analysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MESSENGER-RNA; MELLITUS PATIENTS; TRANSGENIC MICE; IN-VIVO; EXPRESSION; PROTEIN; CELLS; CALMODULIN; INHIBITOR; SEQUENCE AB Diabetes now accounts for > 40% of patients with ESRD. Despite significant progress in understanding diabetic nephropathy, the cellular mechanisms that lead to diabetes-induced renal damage are incompletely defined. For defining changes in protein expression that accompany diabetic nephropathy, the renal proteome of 120-d-old OVE26 transgenic mice with hypoinsulinemia, hyperolycemia, hyperlipidemia, and proteinuria were compared with those of background FVB nondiabetic mice (n = 5). Proteins derived from whole-kidney lysate were separated by two-dimensional PAGE and identified by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Forty-one proteins from 300 Visualized protein spots were differentially expressed in diabetic kidneys. Among these altered proteins, expression of monocyte/neutrophil elastase inhibitor was increased, whereas elastase IIIB was decreased, leading to the hypothesis that elastin expression would be increased in diabetic kidneys. Renal immunohistochemistry for elastin of 325-d-old FVB and OVE26 mice demonstrated marked accumulation of elastin in the macula densa, collecting ducts, and pelvicalyceal epithelia of diabetic kidneys. Elastin immunohistochemistry of human renal biopsies from patients with type 1 diabetes (n - 3) showed increased elastin expression in renal tubular cells and the interstitium but not glomeruli. These results suggest that coordinated changes in elastase inhibitor and elastase expression result in increased tubulointerstitial deposition of elastin in diabetic nephropathy. The identification of these coordinated changes in protein expression in diabetic nephropathy indicates the potential value of proteomic analysis in defining pathophysiology. C1 Univ Louisville, Core Proteom Lab, Kidney Dis Program, Dept Med, Louisville, KY 40292 USA. Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA. Univ Louisville, Dept Pediat, Louisville, KY 40292 USA. Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Vet Affairs Med Ctr, Louisville, KY USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Ohio State Univ, Sch Med, Dept Med, Columbus, OH 43210 USA. RP Thongboonkerd, V (reprint author), Mahidol Univ, Fac Med, Siriraj Hosp, Off Res & Dev,Proteom Ctr,Med Mol Biol Unit, Prannok Rd,12th Floor,Adulyadej Vikrom Bldg, Bangkok 10700, Thailand. EM thongboonkerd@dr.com RI THONGBOONKERD, VISITH /C-6920-2009; McLeish, Kenneth/B-9819-2013; Klein, Jon/B-9833-2013; OI McLeish, Kenneth/0000-0002-7816-3286; Benarafa, Charaf/0000-0002-2049-7769; Epstein, Paul/0000-0002-7006-8954 FU NHLBI NIH HHS [HL66548, R01 HL066548, R01 HL66358-01]; NIDDK NIH HHS [R21 DK06289, R21 DK62086-01] NR 38 TC 68 Z9 85 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2004 VL 15 IS 3 BP 650 EP 662 DI 10.1097/01.ASN.0000115334.65095.9B PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 778BG UT WOS:000189218800016 PM 14978167 ER PT J AU Horkan, C Ahmed, M Liu, ZJ Gazelle, GS Solazzo, SA Kruskal, JB Goldberg, SN AF Horkan, C Ahmed, M Liu, ZJ Gazelle, GS Solazzo, SA Kruskal, JB Goldberg, SN TI Radiofrequency ablation: Effect of pharmacologic modulation of hepatic and renal blood flow on coagulation diameter in a VX2 tumor model SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID ARSENIC TRIOXIDE; IN-VIVO; TISSUE ABLATION; CANCER; SIZE; CARCINOMA; APOPTOSIS; NECROSIS; LESIONS; LIVER AB PURPOSE: To determine whether pharmacologic agents can be used to modulate blood flow in hepatic and renal tumors sufficiently to alter the extent of radiofrequency (RF)-induced coagulation. MATERIALS AND METHODS: VX2 tumors (8-15 mm) were implanted in the liver (n = 25) or kidney (n = 8) of 33 New Zealand White rabbits. RF was applied to tumors for 6 minutes with use of conventional electrodes (125 mA +/- 35; 90 degrees C +/- 21 degrees C tip temperature). In the hepatic model, blood flow was modulated with use of halothane, epinephrine, or arsenic trioxide (2-6 mg/kg). Laser Doppler flowmetry was used to quantify changes in hepatic blood flow. Correlation of blood flow with induced coagulation diameter was performed. RF ablation was then performed in a renal model with and without arsenic trioxide. RESULTS: For liver tumors, halothane and arsenic trioxide reduced blood flow to 40.3 % +/- 17.8 % and 29 % +/- 15 % of normal, respectively, whereas epinephrine increased blood flow to 207.8 % +/- 97.9 %. Correlation of blood flow to coagulation diameter was demonstrated (R-2 = 0.40). Coagulation measured 7 mm I with epinephrine, 10 mm 1 with normal blood flow, 12 mm 3 with halothane, and 13 mm 3 with arsenic trioxide (P < .04 compared with controls). In the renal model, arsenic trioxide decreased blood flow (44 % +/- 16 %) and increased coagulation diameter (10.9 mm +/- 1) compared with controls (84 % 11 % and 7.6 mm 1; P < .01, both comparisons). CONCLUSIONS: RF-induced coagulation necrosis in rabbit hepatic and renal tumors is affected by tumor blood flow. Pharmacologic modulation of tumor blood flow may provide a noninvasive way to decrease blood flow during thermally mediated ablation therapy, potentially enabling the creation of larger zones of coagulation necrosis. C1 Harvard Univ, Dept Radiol, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Lab Minimally Invas Tumor Therapy, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Decis Anal & Technol Assessment Grp, Boston, MA USA. RP Goldberg, SN (reprint author), Harvard Univ, Dept Radiol, Beth Israel Deaconess Med Ctr, Sch Med, 1 Deaconess Rd,WCC 308B, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu FU NCI NIH HHS [R01-CA87992-01A1] NR 32 TC 38 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2004 VL 15 IS 3 BP 269 EP 274 DI 10.1097/01.RVI.0000109396.74740.C4 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 906XI UT WOS:000227677700008 PM 15028812 ER PT J AU Wijelath, ES Rahman, S Murray, J Patel, Y Savidge, G Sobel, M AF Wijelath, ES Rahman, S Murray, J Patel, Y Savidge, G Sobel, M TI Fibronectin promotes VEGF-induced CD34(+) cell differentiation into endothelial cells SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID BLOOD-VESSEL FORMATION; PROGENITOR CELLS; PRECURSOR CELLS; HEMATOPOIETIC-CELLS; GROWTH; ADHESION; NEOVASCULARIZATION; INTEGRIN; ANGIOGENESIS; LETHALITY AB Background: Adult endothelial progenitor cells (EPC) may be a useful source for engineering the endothelialization of vascular grafts. However, the optimal factors that promote differentiation of EPCs into endothelium, remain to be elucidated. The goal of this current report was to determine which extracellular matrix (ECM) protein might modulate or enhance the effects of EPCs on differentiation into mature endothelium. Methods: Human EPCs (CD34(+) cells) were cultured in ECM-coated six-well plates in MCDB-131 medium containing vascular endothelial growth factor (VEGF), insulin-like growth factor-1, and basic fibroblast growth factor. After 21 days, differentiated endothelial colonies were confirmed by immunofluorescence for von Willebrand factor (vWF) and vascular-endothelial (VE)-cadherin and mRNA expression of the endothelial markers FIk-1, vWF, and VE-cadherin. Cell migration toward the VEGF-matrix protein combinations was also measured. Results: As judged by positive staining for endothelial markers vWF and VE-cadherin, the combination of VEGF with fibronectin (FN) produced significantly more endothelial colonies (P <.05) than did collagens I or IV or vitronectin. Defined fragments of IN did not enhance VEGF-mediated effects. Fibrinogen produced intermediate stimulation of differentiation. FN also enhanced VEGF-mediated CD34(+) cell migration. Blockade of alpha5beta1, but not alphavbeta3 or alphavbeta5, inhibited both VEGF-mediated CD34(+) cell differentiation and migration. Conclusions: VEGF and IN together significantly promote the migration and differentiation of CD34(+) cells. This synergism is specific to FN and the alpha5beta1 integrin. Combinations of VEGF and FN may be useful in promoting differentiation of circulating endothelial progenitors into endothelial cells for tissue engineering. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Surg, Div Vasc Surg, Seattle, WA 98195 USA. St Thomas Hosp, GKT Med Sch, Coagulat Res Lab, London, England. RP Wijelath, ES (reprint author), VA Puget Sound Hlth Care Syst, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM errolw@washington.edu NR 30 TC 101 Z9 118 U1 0 U2 6 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2004 VL 39 IS 3 BP 655 EP 660 DI 10.1016/j.jvs.2003.10.042 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 902WJ UT WOS:000227387100024 PM 14981463 ER PT J AU Frahm, N Korber, BT Adams, CM Szinger, JJ Draenert, R Addo, MM Feeney, ME Yusim, K Sango, K Brown, NV SenGupta, D Piechocka-Trocha, A Simonis, T Marincola, FM Wurcel, AG Stone, DR Russell, CJ Adolf, P Cohen, D Roach, T StJohn, A Khatri, A Davis, K Mullins, J Goulder, PJR Walker, BD Brander, C AF Frahm, N Korber, BT Adams, CM Szinger, JJ Draenert, R Addo, MM Feeney, ME Yusim, K Sango, K Brown, NV SenGupta, D Piechocka-Trocha, A Simonis, T Marincola, FM Wurcel, AG Stone, DR Russell, CJ Adolf, P Cohen, D Roach, T StJohn, A Khatri, A Davis, K Mullins, J Goulder, PJR Walker, BD Brander, C TI Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PLASMA VIRAL LOAD; TYPE-1 SUBTYPE-C; CELL RESPONSES; HIV-1 INFECTION; DISEASE PROGRESSION; CD8-T-CELL MEMORY; IMMUNE-RESPONSES; CD4-T-CELL HELP; HLA-A AB Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most Affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting class I molecules. The present study thus identifies factors that contribute to the immunogenicity of these highly targeted and relatively conserved sequences in HIV that may represent promising vaccine candidates for ethnically heterogeneous populations. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Charlestown, MA USA. Fenway Community Hlth Ctr, Boston, MA USA. Lemuel Shattuck Hosp, Boston, MA USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Queen Elizabeth Hosp, Bridgetown, Barbados. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Brander, C (reprint author), Partners AIDS Res Ctr, 5th Floor MGH E,5239,149 13th St, Charlestown, MA 02129 USA. EM brander@helix.mgh.harvard.edu OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 FU PHS HHS [N01-A1-15422] NR 55 TC 224 Z9 235 U1 3 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2004 VL 78 IS 5 BP 2187 EP 2200 DI 10.1128/JVI.78.5.2187-2200.2004 PG 14 WC Virology SC Virology GA 775AV UT WOS:000189019300003 PM 14963115 ER PT J AU Wood, JC Quinn, G Suling, KA Oldmixon, BA Van Tine, BA Cina, R Arn, S Huang, CA Scobie, L Onions, DE Sachs, DH Schuurman, HJ Fishman, JA Patience, C AF Wood, JC Quinn, G Suling, KA Oldmixon, BA Van Tine, BA Cina, R Arn, S Huang, CA Scobie, L Onions, DE Sachs, DH Schuurman, HJ Fishman, JA Patience, C TI Identification of exogenous forms of human-tropic porcine endogenous retrovirus in miniature swine SO JOURNAL OF VIROLOGY LA English DT Article ID LARGE WHITE-PIG; HUMAN-CELLS; NO EVIDENCE; NUCLEOTIDE-SEQUENCES; INFECTION; XENOTRANSPLANTATION; LEUKEMIA; TRANSMISSION; RECIPIENTS; PERV AB The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B in certain human cell lines indicates that PERV may pose an infectious risk in clinical xenotransplantation. We have previously reported that human-tropic PERVs isolated from infected human cells following cocultivation with miniature swine peripheral blood mononuclear cells (PBMC) are recombinants of PERV-A with PERV-C. Here, we report that these recombinants are exogenous viruses in miniature swine; i.e., they are not present in the germ line DNA. These viruses were invariably present in miniature swine that transmitted PERV to human cells and were also identified in some miniature swine that lacked this ability. These data, together with the demonstration of the absence of both replication-competent PERV-A and recombinant PERV-A/C loci in the genome of miniature swine (L. Scobie, S. Taylor, J. C. Wood, K. M. Suling, G. Quinn, C. Patience, H.-J. Schuurman, and D. E. Onions, J. Virol. 78:2502-2509,2004), indicate that exogenous PERV is the principal source of human-tropic virus in these animals. Interestingly, strong expression of PERV-C in PBMC correlated with an ability of the PBMC to transmit PERV-A/C recombinants in vitro, indicating that PERV-C may be an important factor affecting the production of human-tropic PERV. In light of these observations, the safety of clinical xenotransplantation from miniature swine will be most enhanced by the utilization of source animals that do not transmit PERV to either human or porcine cells. Such animals were identified within the miniature swine herd and may further enhance the safety of clinical xenotransplantation. C1 Immerge BioTherapeut Inc, Cambridge, MA 02139 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Charlestown, MA 02129 USA. Univ Glasgow, Dept Vet Pathol, Glasgow G61 1QH, Lanark, Scotland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Patience, C (reprint author), Immerge BioTherapeut Inc, 300 Technol Sq, Cambridge, MA 02139 USA. EM clive.patience@immergebt.com FU NIAID NIH HHS [2 R44 AI48349-02, 5T32-AI07529-04, P01 AI045897, P01-AI45897, T32 AI007529] NR 38 TC 84 Z9 86 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2004 VL 78 IS 5 BP 2494 EP 2501 DI 10.1128/JVI.78.5.2494-2501.2004 PG 8 WC Virology SC Virology GA 775AV UT WOS:000189019300034 PM 14963150 ER PT J AU Lu, R Nakajima, N Hofmann, W Benkirane, M Jeang, KT Sodroski, J Engelman, A AF Lu, R Nakajima, N Hofmann, W Benkirane, M Jeang, KT Sodroski, J Engelman, A TI Simian virus 40-based replication of catalytically inactive human immunodeficiency virus type 1 integrase mutants in nonpermissive T cells and monocyte-derived macrophages (vol 78, pg 658, 2004) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Lu, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2004 VL 78 IS 5 BP 2654 EP 2654 DI 10.1128/JVI.78.5.2654.2004 PG 1 WC Virology SC Virology GA 775AV UT WOS:000189019300059 ER PT J AU Ali, SH Kasper, JS Arai, T DeCaprio, JA AF Ali, SH Kasper, JS Arai, T DeCaprio, JA TI Cu17/p185/p193 binding to simian virus 40 large T antigen has a role in cellular transformation SO JOURNAL OF VIROLOGY LA English DT Article ID SV40 LARGE-T; UBIQUITIN LIGASE ACTIVITY; F-BOX PROTEIN; MOUSE EMBRYO FIBROBLASTS; PRB-RELATED PROTEINS; I-KAPPA-B; WILD-TYPE; CYCLIN-E; MEDIATED TRANSFORMATION; SV40-TRANSFORMED CELLS AB Simian virus 40 large T antigen (TAg) is a viral oncoprotein that can promote cellular transformation. TAg's transforming activity results in part by binding and inactivating key tumor suppressors, including p53 and the retinoblastoma protein (pRb). We have identified a TAg-associated 185-kDa protein that has significant homology to the cullin family of E3 ubiquitin ligases. TAg binds to an SCF-like complex that contains p185/Cu17, Rbx1, and the F box protein Fbw6. This SCF-like complex binds to an N-terminal region of TAg. Several p185/Cu17-binding-deficient mutants of TAg were generated that retained binding to pRb and p53 and were capable of overcoming Rb-mediated repression of E2F transcription. Despite binding to pRb and p53, these p185/Cu17-binding-defective mutants of TAg were unable to transform primary mouse embryo fibroblasts. Cells expressing p185/Cu17-binding-defective mutants of TAg were unable to grow to high density or grow in an anchorage-independent manner as determined by growth in soft agar. Considering the significance of other TAg-interacting proteins in regulation of the cell cycle, p185/Cu17 may also regulate an important growth control pathway. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer 457,44 Binney St, Boston, MA 02115 USA. EM james_decaprio@dfci.harvard.edu FU NCI NIH HHS [R01CA093804, R01 CA093804, P01CA50661, P01 CA050661] NR 67 TC 52 Z9 56 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2004 VL 78 IS 6 BP 2749 EP 2757 DI 10.1128/JVI.78.6.2749-2757.2004 PG 9 WC Virology SC Virology GA 800QP UT WOS:000220043100011 PM 14990695 ER PT J AU Manotham, K Tanaka, T Matsumoto, M Ohse, T Inagi, R Miyata, T Kurokawa, K Fujita, T Ingelfinger, JR Nangaku, M AF Manotham, K Tanaka, T Matsumoto, M Ohse, T Inagi, R Miyata, T Kurokawa, K Fujita, T Ingelfinger, JR Nangaku, M TI Transdifferentiation of cultured tubular cells induced by hypoxia SO KIDNEY INTERNATIONAL LA English DT Article DE tubuloitnterstitial fibrosis; transdifferentiation; epithelial mesenchymal transformation; myofibroblast; hypoxia; smooth muscle actin ID RENAL INTERSTITIAL FIBROSIS; EPITHELIAL-MYOFIBROBLAST TRANSDIFFERENTIATION; GENE-EXPRESSION; THROMBOTIC MICROANGIOPATHY; OBSTRUCTIVE NEPHROPATHY; TRANSCRIPTION FACTORS; REMNANT KIDNEY; GROWTH-FACTOR; TGF-BETA; INJURY AB Background. Tubulointerstitial fibrosis leads to progressive kidney disease and, ultimately, may result in end-stage renal disease (ESRD). Myofibroblasts, which express alpha-smooth muscle actin (alpha-SMA) in their cytoplasm, regulate renal fibrogenesis. Recent studies suggest that certain interstitial myofibroblasts derive from renal tubular cells that have undergone epithelial-mesenchymal transformation (EMT) (transdifferentiation). However, the role(s) of hypoxia, which is involved in progressive kidney disease, on tubular EMT remains unclear. Methods Immortalized rat proximal tubular cells (IRPTC) were cultured in normobaric hypoxia (1% O-2) for 3, 6, or 15 days, with match control in normoxic conditions. alpha-SMA, vimentin, and desmin chosen as markers of EMT were measured by immunocytochemistry and immunoblots collagen I production and cell motility were chosen as functional assays. Various concentrations of cobaltous chloride (CoCl2) were used as hypoxic mimickers. In vivo studies were carried out in a chronic ischemic kidney model. Results. Immunohistochemical studies revealed increased expression of alpha-SMA. Striking morphologic changes were detected after 6 days of hypoxia for alpha-SMA-positive fibroblast-like cells (SMA + fib) and after 15 days for alpha-SMA-positive myofibroblast-like cells (SMA + myo). Immunoblots confirmed these findings. Collagen I production increased in a time-dependent manner parallel to alpha-SMA expression. Cell motility assays demonstrated that transformed cells had higher migratory capacity than normal tubular cells. Cobaltous salt also induced alpha-SMA and collagen I synthesis. Chronic ischemic kidney revealed in vivo tubular EMT at day 7. Conclusion. Hypoxia can induce tubular EMT. This process may play an important role in progression of kidney disease. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo, Japan. Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 25911, Japan. Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan. Massachusetts Gen Hosp, Dv Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 NR 59 TC 130 Z9 147 U1 1 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2004 VL 65 IS 3 BP 871 EP 880 DI 10.1111/j.1523-1755.2004.00461.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 772WL UT WOS:000188865000011 PM 14871406 ER PT J AU Roman, GC Royall, DR AF Roman, GC Royall, DR TI A diagnostic dilemma: is "Alzheimer's dementia" Alzheimer's disease, vascular dementia, or both? SO LANCET NEUROLOGY LA English DT Editorial Material ID POPULATION; EVOLUTION C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM ROMANG@uthscsa.edu NR 10 TC 26 Z9 26 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD MAR PY 2004 VL 3 IS 3 BP 141 EP 141 DI 10.1016/S1474-4422(04)00674-X PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 802MK UT WOS:000220167400012 PM 14980525 ER PT J AU Kezirian, EJ Weaver, EM Yueh, B Deyo, RA Khuri, SF Daley, J Henderson, W AF Kezirian, EJ Weaver, EM Yueh, B Deyo, RA Khuri, SF Daley, J Henderson, W TI Incidence of serious complications after uvulopalatopharyngoplasty SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the Triological-Society CY MAY 04-06, 2003 CL NASHVILLE, TN SP Triolog Soc DE obstructive sleep apnea; complications; mortality; palate surgery; uvulopalatopharyngoplasty; veterans; VA ID OBSTRUCTIVE SLEEP-APNEA; SURGICAL-TREATMENT; CARE; MANAGEMENT; SURGERY AB Objectives: Uvulopalatopharyngoplasty (UPPP) is the most common surgical treatment for obstructive sleep apnea (OSA). Anatomic and physiologic abnormalities associated with OSA can make perioperative management difficult. Only single-site case series provide current estimates of the incidence of perioperative complications, with a pooled crude serious complication rate of 3.5% and a crude mortality rate of 0.4%. The primary objective of this study was to calculate the incidence of perioperative morbidity and mortality in a large, multisite cohort of UPPP patients. Study Design. Prospective cohort study of adults undergoing inpatient LTPPP with or without other concurrent procedures Methods: The serious complication and 30-day mortality rates were calculated from the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program database of prospectively collected outcomes of all VA inpatient surgeries nationally 1991 to 2001. Serious complications were defined by 15 specific life-threatening complications. Deaths were captured whether the patient was in the hospital or discharged. Results: Veteran patients (n = 3130) had a mean age of 50 years and were predominantly male (97%). The serious nonfatal complication rate was 1.5% (47/3,130) (95% confidence interval [CI] 1.1%, 1.9%). The 30-day mortality rate was 0.2% (7/3130) (95% Cl 0.1%, 0.4%). There was no significant effect of year of surgery or patient age on the risk of serious complication or death. Conclusion. The incidence of serious nonfatal complications and 30-day mortality after UPPP are 1.5% and 0.2%, respectively, in a large cohort of LTPPP patients at veteran hospitals. C1 Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Hlth Sci, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. Harvard Med Sch, Boston, MA USA. Tenet Hlth Care, Dallas, TX USA. Stanford Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Stanford, CA 94305 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Weaver, EM (reprint author), 112-OTO,1660 S Columbian Way, Seattle, WA 98108 USA. EM eweaver@u.washington.edu FU NHLBI NIH HHS [K23 HL068849, K23 HL068849-01A2]; NIDCD NIH HHS [T32 DC000018] NR 11 TC 52 Z9 72 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2004 VL 114 IS 3 BP 450 EP 453 DI 10.1097/00005537-200403000-00012 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 811YA UT WOS:000220806000010 PM 15091217 ER PT J AU Lin, FH Kwong, KK Belliveau, JW Wald, LL AF Lin, FH Kwong, KK Belliveau, JW Wald, LL TI Parallel imaging reconstruction using automatic regularization SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article ID SENSE; COIL; MRI; DESIGN; ARRAY; SMASH AB Increased spatiotemporal resolution in MRI can be achieved by the use of parallel acquisition strategies, which simultaneously sample reduced k-space data using the information from multiple receivers to reconstruct full-FOV images. The price for the increased spatiotemporal resolution in parallel MRI is the degradation of the signal-to-noise ratio (SNR) in the final reconstructed images. Part of the SNR reduction results when the spatially correlated nature of the information from the multiple receivers destabilizes the matrix inversion used in the reconstruction of the full-FOV image. In this work, a reconstruction algorithm based on Tikhonov regularization is presented that reduces the SNR loss due to geometric correlations in the spatial information from the array coil elements. Reference scans are utilized as a priori information about the final reconstructed image to provide regularized estimates for the reconstruction using the L-curve technique. This automatic regularization method reduces the average g-factors in phantom images from a two-channel array from 1.47 to 0.80 in twofold sensitivity encoding (SENSE) acceleration. In vivo anatomical images from an eight-channel system show an averaged g-factor reduction of 1.22 to 0.84 in 2.67-fold acceleration. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Lin, FH (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. EM fhlin@mit.edu RI Lin, Fa-Hsuan/G-6988-2012; Wald, Lawrence/D-4151-2009 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41RR14075] NR 17 TC 156 Z9 158 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 2004 VL 51 IS 3 BP 559 EP 567 DI 10.1002/mrm.10718 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 800BF UT WOS:000220003200018 PM 15004798 ER PT J AU Damschroder, LJ Baron, J Hershey, JC Asch, DA Jepson, C Ubel, PA AF Damschroder, LJ Baron, J Hershey, JC Asch, DA Jepson, C Ubel, PA TI The validity of person tradeoff measurements: Randomized trial of computer elicitation versus face-to-face interview SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 19-23, 2002 CL BALTIMORE, MARYLAND SP Soc Med Decis Making DE person tradeoff; utility assessment; computer elicitation; cost-effectiveness; randomized trial; Internet survey ID LONGITUDINAL DATA-ANALYSIS; WEB-BASED SURVEYS; HEALTH-CARE; UTILITY ELICITATIONS; OFF ELICITATIONS; SOCIETAL VALUE; INTERNET; VALUES; BIASES; SCALE AB Can person tradeoff (PTO) value judgments be elicited by a computer, or is a face-to-face interview needed? The authors randomly assigned 95 subjects to interview or computer methods for the PTO, a valuation measure that is often difficult for subjects. They measured relative values of foot numbness, leg paralysis, and quadriplegia (all 3 pairs) at 2 reference group sizes (10 or 100). Relative values did not differ between computer and interview. Overall, 21% of responses were equality responses, 13% were high extreme values, and 5% violated ordinal criteria. The groups did not differ in these measures. The authors also assessed consistency across reference group size (10 v. 100). Although relative values were significantly lower for 100 than for 10, mode did not influence the size of this effect. Subjects made, on average, equally consistent judgments for the 3 comparisons. A computerized PTO elicitation protocol produced results of similar quality to that of a face-to-face interview. C1 Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv Res & Ctr Practice Management & Outc, Ann Arbor, MI USA. Univ Michigan, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Damschroder, LJ (reprint author), Univ Michigan, Div Gen Internal Med, 300 N Ingalls,Room 7C27, Ann Arbor, MI 48109 USA. OI Asch, David/0000-0002-7970-286X; Damschroder, Laura/0000-0002-3657-8459 FU NICHD NIH HHS [R01 HD38963] NR 48 TC 17 Z9 17 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAR-APR PY 2004 VL 24 IS 2 BP 170 EP 180 DI 10.1177/0272989X04263160 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 805VA UT WOS:000220392600006 PM 15090103 ER PT J AU Regestein, QR Friebely, J Shifren, JL Scharf, MB Wiita, B Carver, J Schiff, I AF Regestein, QR Friebely, J Shifren, JL Scharf, MB Wiita, B Carver, J Schiff, I TI Self-reported sleep in postmenopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE menopause; sleep; cognition; psychological symptoms; hyperarousal ID QUALITY-OF-LIFE; REPLACEMENT THERAPY; DAYTIME ALERTNESS; INSOMNIA; DISTURBANCE; DEPRESSION; MENOPAUSE; QUESTIONNAIRE; COMPLAINTS; DISORDERS AB Objective: We aimed to find how self-reported sleep (measured by the St. Mary's Hospital Sleep Questionnaire) in postmenopausal women having hot flash activity was related to objective sleep (actigraphy), psychological and somatic symptoms [Women's Health Questionnaire (WHQ)], and cognitive test performance (computerized tests). A secondary aim was to find if self-reported sleep showed expected correlations with hyperarousal (Hyperarousal Scale). Design: Drug trial baseline data from 88 healthy, postmenopausal women were retrospectively analyzed. Multivariate regression was used to adjust for confounder variables and test whether differences in self-reported sleep measures were systematically associated with differences in objective sleep, WHQ symptom measures, or cognitive test performance scores. Results: Increased self-report scores for low sleep quality were associated with an increased risk of WHQ symptoms and reduced cognitive test performance. Self-reported sleep measures showed little correlation with their analogous objective measures. Self-reported low sleep quality proved most closely associated with the WHQ symptoms of tiredness, clumsiness, and difficulty concentrating. Women whose self-reported sleep-onset latency times were longer than the median overestimated their objective sleep onset time by 30 min, whereas the other women underestimated theirs by 15 min (P < 0.0001). Women whose self-reported total sleep was longer or shorter than the median, respectively, underestimated objective sleep times by 9 and 71 min (P < 0.0001). High hyperarousal scores were associated with underestimations of objective sleep. Conclusion: Self-reports of lower sleep quality were associated with increased WHQ psychological and somatic symptom measures and decreased cognitive test performance more than with differences in objective sleep. Self-reported trouble sleeping may signal problems independent from objectively low sleep quality, such as subjective distress or diminished cognitive function. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tri State Sleep Disorders Ctr, Cleveland, OH USA. Johnson & Johnson, Skillman, NJ USA. RP Regestein, QR (reprint author), 75 Francis St, Boston, MA 02115 USA. EM qregestein@partners.org NR 38 TC 46 Z9 49 U1 5 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAR-APR PY 2004 VL 11 IS 2 BP 198 EP 207 DI 10.1097/01.GME.0000097741.18446.3E PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 804BO UT WOS:000220274400011 PM 15021450 ER PT J AU Bykowski, J Kollias, N LaMuraglia, GM AF Bykowski, J Kollias, N LaMuraglia, GM TI Evaluation of peripheral arterial occlusive disease and postsurgical viability using reflectance spectroscopy of skin SO MICROVASCULAR RESEARCH LA English DT Article DE peripheral vascular disease; diagnosis; reactive hyperemia; ischemia; visible reflectance spectroscopy ID CRITICAL LIMB ISCHEMIA; REACTIVE HYPEREMIA; OXYGEN SUFFICIENCY; HUMAN MELANIN; INVIVO; MICROCIRCULATION; INFLAMMATION; HEMOGLOBIN; DIAGNOSIS; BLOOD AB Hypothesis: Stress-induced changes in skin microcirculation allow staging of peripheral arterial vascular pathology using diffuse reflectance spectroscopy (DRS) of the skin. Design and Methods: The changes in relative concentration of oxyhemoglobin and deoxyhemoglobin in the cutaneous microvasculature were assessed at rest, during limb elevation, dependency, and cuff-mediated reactive hyperemia for the forearm of 25 normal subjects and 105 feet of patients with peripheral arterial occlusive disease (PAOD) (normal = 28, claudication = 34, limb threatening ischemia = 44). Thirty-four patients who had revascularization procedures were again evaluated within the first week postoperatively. Results: Two measurements correlated with clinical staging: (1) the relative absorbance of oxyhemoglobin after 225 s of limb dependency and (2) the time to reach 50% of peak reactive hyperemia response (Spearman's rank: r(s) = 0.625, P < 0.001). Using these criteria alone, ischemic limbs were identified to a sensitivity of 69% and specificity of 95%. Significant post-revascularization improvement was identified in 14 of 34 patients' legs which had previously been classified as limb-threatening ischemia (n = 14, W = 105, P < 0.001). Conclusions: These simple bedside evaluations of the superficial skin microvasculature allow staging of large vessel vascular insufficiency and may suggest and differentiate focal areas of tissue at risk for ulceration or necrosis. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Surg Serv, Boston, MA 02114 USA. RP Bykowski, J (reprint author), Univ Vermont, Coll Med, 89 Beaumont Ave,Given Box 90, Burlington, VT 05405 USA. EM Julie.Bykowski@uvm.edu NR 25 TC 10 Z9 10 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAR PY 2004 VL 67 IS 2 BP 152 EP 158 DI 10.1016/j.mvr.2003.11.003 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 804IR UT WOS:000220292900006 PM 15020206 ER PT J AU Maguen, S Litz, BT Wang, JL Cook, M AF Maguen, S Litz, BT Wang, JL Cook, M TI The stressors and demands of peacekeeping in Kosovo: Predictors of mental health response SO MILITARY MEDICINE LA English DT Article ID PERSONNEL; DISORDER; SOMALIA; PTSD AB U.S. soldiers' appraisal and experience of the Kosovo peacekeeping mission is described. Using a prospective design, we evaluated the prevalence, severity, and predictors of several mental health outcomes at redeployment. We found that peacekeepers frequently were exposed to potentially traumatizing and other stressful events while in Kosovo, but on average, their appraisal of those events was moderate. Postdeployment psychopathology was also low-soldiers endorsed more severe mental health difficulties at predeployment, which suggests anticipatory negative affect. After controlling for the impact of predeployment stressors, we examined the contribution of potentially traumatizing events, general overseas military duty stressors, negative aspects of peacekeeping roles, and generic positive military experiences, including morale, to explain variance in four outcomes: post-traumatic stress disorder, depression, hostility and aggression problems, and problems with alcohol abuse. Findings indicate that hostility and drinking may be more chronic problems that emerge during stressful times, whereas depression and post-traumatic stress disorder symptoms may be more apt to fluctuate and are associated with potentially traumatizing experiences during peacekeeping. The implications and limitations of the study are discussed. C1 VA Boston Hlth Care Syst, Jamaica Plain, MA 02130 USA. RP Maguen, S (reprint author), VA Boston Hlth Care Syst, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. RI Dopko, Rae/J-7437-2015 NR 16 TC 47 Z9 47 U1 0 U2 5 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 2004 VL 169 IS 3 BP 198 EP 206 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 019IR UT WOS:000235829300009 PM 15080239 ER PT J AU Daniron-Rodriguez, J White-Kazemipour, W Washington, D Villa, VM Dhanani, S Harada, ND AF Daniron-Rodriguez, J White-Kazemipour, W Washington, D Villa, VM Dhanani, S Harada, ND TI Accessibility and acceptability of the Department of Veteran Affairs health care: Diverse veterans' perspectives SO MILITARY MEDICINE LA English DT Article ID PATIENT SATISFACTION; MINORITY VETERANS; VA; SERVICES; SYSTEM; DETERMINANTS; COVERAGE; ACCESS AB Objectives: Diverse veteran's perspectives on the accessibility and acceptability of the Department of Veteran Affairs (VA) health services are presented. Methods: The qualitative methodology uses 16 focus groups (N = 178) stratified by war cohort (World War II and Korean Conflict versus Vietnam War and Persian Gulf War) and four ethnic/racial categories (African American, Asian American, European American, Hispanic American). Results: Five themes emerged regarding veterans' health care expectations: (1) better information regarding available services, (2) sense of deserved benefits, (3) concern about welfare stigma, (4) importance of physician attentiveness, and (5) staff respect for patients as veterans. Although veterans' ethnic/racial backgrounds differentiated their military experiences, it was the informants' veteran identity that framed what they expected of VA health services. Conclusions: Accessibility and acceptability of VA health care is related to veterans' perspectives of the nature of their entitlement to service. Provider education and customer service strategies should consider the identified factors to increase access to VA as well as improve veterans' acceptance of the care. C1 Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Policy & Social Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Anthropol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Daniron-Rodriguez, J (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. NR 25 TC 0 Z9 0 U1 4 U2 4 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD MAR PY 2004 VL 169 IS 3 BP 243 EP 250 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 019IR UT WOS:000235829300017 ER PT J AU Heinrich, MC AF Heinrich, MC TI Targeting FLT3 kinase in acute myelogenous leukemia: Progress, perils, and prospects SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE FLT3; tyrosine kinase; kinase inhibitor; AML; KIT; PDGFR ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; RECEPTOR TYROSINE KINASE; ACUTE PROMYELOCYTIC LEUKEMIA; CELLS IN-VITRO; HEMATOPOIETIC PROGENITOR CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; TRANS-RETINOIC ACID; GASTROINTESTINAL STROMAL TUMORS; HISTONE DEACETYLASE INHIBITORS AB Activating mutations of the FLT3 receptor tyrosine kinase are the most common recurring genetic abnormality in acute myelogenous leukemia (AM). Inhibition of FLT3 kinase activity by small molecule inhibitors has been proposed as a novel therapeutic approach AML. The pre-clinical and clinical development of candidate FLT3 inhibitors will be reviewed. C1 Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. RP Heinrich, MC (reprint author), R&D-19,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM heinrich@ohsu.edu NR 149 TC 8 Z9 8 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD MAR PY 2004 VL 4 IS 3 BP 255 EP 271 DI 10.2174/1389557043487394 PG 17 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 890BM UT WOS:000226486700003 PM 15032673 ER PT J AU Cowan-Jacob, SW Guez, V Fendrich, G Griffin, JD Fabbro, D Furet, P Liebetanz, J Mestan, J Manley, PW AF Cowan-Jacob, SW Guez, V Fendrich, G Griffin, JD Fabbro, D Furet, P Liebetanz, J Mestan, J Manley, PW TI Imatinib (STI571) resistance in chronic myelogenous leukemia: Molecular basis of the underlying mechanisms and potential strategies for treatment SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; BCR-ABL ONCOGENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; FARNESYL TRANSFERASE INHIBITOR; INTEGRIN-MEDIATED REGULATION; BCR/ABL-TRANSFORMED CELLS; C-ABL; HEMATOPOIETIC-CELLS AB Following the paradigm set by ST1571, protein tyrosine kinase inhibitors are emerging as a promising class of drugs, capable of modulating intracellular signaling and demonstrating therapeutic potential for the treatment of proliferative diseases. Although the majority of chronic phase CML patients treated with ST1571 respond, some patients, especially those with more advanced disease, relapse. This article reviews the reasons for relapse and, in particular, analyses resistance resulting from Bcr-Abl tyrosine kinase domain mutations at the molecular level. Arguments are based upon the structure of the ST1571-Abl complex, which is compared to the crystal structures of PD173955-Abl and PD180970-Abl, which bind to the kinase differently. Strategies to potentially circumvent or overcome resistance are discussed. C1 Novartis Inst Biomed Res, CH-4057 Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Manley, PW (reprint author), Novartis Inst Biomed Res, WKL-136-4-86,Klybeckstr 141, CH-4057 Basel, Switzerland. EM paul.manley@pharma.novartis.com NR 132 TC 114 Z9 118 U1 3 U2 14 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD MAR PY 2004 VL 4 IS 3 BP 285 EP 299 DI 10.2174/1389557043487321 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 890BM UT WOS:000226486700005 PM 15032675 ER PT J AU Panta, GR Kaur, S Cavin, LG Cortes, ML Mercurio, F Lothstein, L Sweatman, TW Israel, M Arsura, M AF Panta, GR Kaur, S Cavin, LG Cortes, ML Mercurio, F Lothstein, L Sweatman, TW Israel, M Arsura, M TI ATM and the catalytic subunit of DNA-dependent protein kinase activate NF-kappa B through a common MEK extracellular signal-regulated kinase/p90(rsk) signaling pathway in response to distinct forms of DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; RIBOSOMAL S6 KINASE; CELL-CYCLE ARREST; IONIZING-RADIATION; RADIOSENSITIZING AGENT; EPITHELIAL-CELLS; IKK COMPLEX; APOPTOSIS; ALPHA; INHIBITION AB We have identified a novel pathway of ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK) signaling that results in nuclear factor kappaB (NF-kappaB) activation and chemoresistance in response to DNA damage. We show that the anthracycline doxorubicin (DOX) and its congener N-benzyladriamycin (AD 288) selectively activate ATM and DNA-PK, respectively. Both ATM and DNA-PK promote sequential activation of the mitogen-activated protein kinase (MAPK)/p90(rsk) signaling cascade in a p53-independent fashion. In turn, p90(rsk) interacts with the IkappaB kinase 2 (IKK-2) catalytic subunit of IKK, thereby inducing NF-kappaB activity and cell survival. Collectively, our findings suggest that distinct members of the phosphatidylinositol kinase family activate a common prosurvival MAPK/IKK/NF-kappaB pathway that opposes the apoptotic response following DNA damage. C1 Univ Tennessee, Coll Med, Dept Pharmacol, Ctr Anticanc Drug Res,Canc Inst, Memphis, TN 38163 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit,Dept Neurol, Charlestown, MA 02129 USA. Celgene Signal Res Div, San Diego, CA 92121 USA. RP Arsura, M (reprint author), Univ Tennessee, Coll Med, Dept Pharmacol, Ctr Anticanc Drug Res,Canc Inst, 874 Union Ave, Memphis, TN 38163 USA. EM marsura@utmem.edu FU NCI NIH HHS [CA78616, CA78616-S1, R01 CA078616] NR 55 TC 95 Z9 99 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2004 VL 24 IS 5 BP 1823 EP 1835 DI 10.1128/MCB.24.5.1823-1835.2004 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779PP UT WOS:000189309500001 PM 14966265 ER PT J AU Tseng, YH Kriauciunas, KM Kokkotou, E Kahn, CR AF Tseng, YH Kriauciunas, KM Kokkotou, E Kahn, CR TI Differential roles of insulin receptor substrates in brown adipocyte differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-I; 3T3-L1 ADIPOGENESIS; GLUCOSE-HOMEOSTASIS; SIGNAL TRANSDUCERS; EXPRESSION; MICE; CELL; GENE; IRS-1 AB Insulin promotes adipocyte differentiation via a complex signaling network involving multiple insulin receptor substrates (IRSs). In cultured brown preadipocytes, expression of IRS-1 and IRS-2 mRNAs and proteins was at relatively high levels before and after differentiation into mature fat cells, while IRS-3 transcript was not detectable in preadipocytes but increased during the course of differentiation, and IRS-4 mRNA was barely detected in both states. To determine more precisely the roles of various IRS proteins in adipogenesis, we established and characterized brown preadipocyte cell lines from wild-type and IRS knockout (KO) animals. While wild-type, IRS-2 KO, and IRS-4 KO cells fully differentiated into mature adipocytes, IRS-3 KO cells showed a moderate defect in differentiation and IRS-1 KO cells exhibited a severe defect in the process. Cells lacking both IRS-1 and IRS-3 completely failed to differentiate. Expression of the adipogenic markers peroxisome proliferator-activated receptor gamma (PPARgamma), CCAAT/enhancer-binding protein alpha, fatty acid synthase, glucose transporter 4, and the transcription factor signal transducer and activator of transcription 5, as well as the brown-fat-specific markers PPARgamma coactivator 1 alpha and uncoupling protein 1, mirrored the differentiation pattern. Reconstitution of the IRS-1 KO cells with IRS-1 and IRS-4, but not IRS-2 or IRS-3, compensated for the lack of differentiation in IRS-1 KO cells. A chimeric molecule containing the N terminus of IRS-1 and the C terminus of IRS-2, but not one with the N terminus of IRS-2 and the C terminus of IRS-1, also rescued differentiation. Expression of Wnt 10a, a molecule known to inhibit adipogenesis, was dramatically increased in the IRS-1 KO cells, and this could be reduced by overexpression of IRS-1 or IRS-4, which was correlated with restoration of differentiation. These data indicate that both IRS-1 and -3 play important roles in the differentiation of brown adipocytes and that the N terminus of IRS-1 is more important for this function of the molecule. Although IRS-4 is not essential for the process, overexpression of IRS-4 can compensate for the deficiency in differentiation in IRS-1 KO cells. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK033201, R01 DK055545, DK33201, DK101183, DK55545, F32 DK101183] NR 46 TC 93 Z9 101 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2004 VL 24 IS 5 BP 1918 EP 1929 DI 10.1128/MCB.24.5.1918-1929.2004 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779PP UT WOS:000189309500009 PM 14966273 ER PT J AU Hahm, KM Sum, EYM Fujiwara, Y Lindeman, GJ Visvader, JE Orkin, SH AF Hahm, KM Sum, EYM Fujiwara, Y Lindeman, GJ Visvader, JE Orkin, SH TI Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner deaf-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ONLY PROTEIN; HOMEOTIC TRANSFORMATIONS; HOMEODOMAIN PROTEINS; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; CRE RECOMBINASE; SAND DOMAIN; GENE; EXPRESSION; IDENTIFICATION AB LMO4 belongs to a family of transcriptional regulators that comprises two zinc-binding LIM domains. LIM-only (LMO) proteins appear to function as docking sites for other factors, leading to the assembly of multiprotein complexes. The transcription factor Deaf-1/NUDR has been identified as one partner protein of LMO4. We have disrupted the Lmo4 and Deaf-1 genes in mice to define their biological function in vivo. All Lmo4 mutants died shortly after birth and showed defects within the presphenoid bone, with 50% of mice also exhibiting exencephaly. Homeotic transformations were observed in Lmo4-null embryos and newborn mice, but with incomplete penetrance. These included skeletal defects in cervical vertebrae and the rib cage. Furthermore, fusions of cranial nerves IX and X and defects in cranial nerve V were apparent in some Lmo4(-/-) and Lmo4(+/-) mice. Remarkably, Deaf-1 mutants displayed phenotypic abnormalities similar to those observed in Lmo4 mutants. These included exencephaly, transformation of cervical segments, and rib cage abnormalities. In contrast to Lmo4 nullizygous mice, nonexencephalic Deaf-1 mutants remained healthy. No defects in the sphenoid bone or cranial nerves were apparent. Thus, Lmo4 and Deaf-1 mutant mice exhibit overlapping as well as distinct phenotypes. Our data indicate an important role for these two transcriptional regulators in pathways affecting neural tube closure and skeletal patterning, most likely reflecting their presence in a functional complex in vivo. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Walter & Eliza Hall Inst Med Res, VBCRC Lab, Melbourne, Vic 3050, Australia. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM Stuart_Orkin@dfci.harvard.edu NR 44 TC 83 Z9 89 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2004 VL 24 IS 5 BP 2074 EP 2082 DI 10.1128/MCB.24.5.2074-2082.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 779PP UT WOS:000189309500022 PM 14966286 ER PT J AU Tian, M Jones, DA Smith, M Shinkura, R Alt, FW AF Tian, M Jones, DA Smith, M Shinkura, R Alt, FW TI Deficiency in the nuclease activity of xeroderma pigmentosum G in mice leads to hypersensitivity to UV irradiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; DNA-REPAIR; XPG PROTEIN; COCKAYNE-SYNDROME; SWITCH REGIONS; GROWTH FAILURE; ULTRAVIOLET-B; GENE; LACKING; TRANSCRIPTION AB Xeroderma pigmentosum (XP) is a human disorder which is characterized by hypersensitivity to sunlight and elevated incidence of skin cancer. The disease is caused by mutations in genes that encode components of the nucleotide excision repair pathway. The gene product of XP complementation group G (XPG) is a structure-specific endonuclease which makes an incision 3' to DNA photoproducts and other helix-distorting DNA adducts. In addition, the XPG protein has been implicated in transcription and repair of oxidative DNA damage. Moreover, XPG is capable of cleaving R loops in vitro, a potential intermediate during immunoglobulin heavy-chain class switch recombination. Due to its multiple functions, complete elimination of XPG in mice results in severe postnatal growth defects and premature death. To understand the contribution of the XPG nuclease activity to its function in vivo, we introduced a point mutation into the mouse XPG gene which inactivates the nuclease catalytic site but leaves the remainder of the protein intact. The XPG nuclease-deficient animals develop normally and exhibit no obvious defect in class switch recombination. However, the mutant mice are hypersensitive to UV irradiation. This phenotype suggests that the nuclease activity of XPG is required only for nucleotide excision repair and that other regions of the protein perform independent functions. C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, 320 Longwood Ave, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NIAMS NIH HHS [P30 AR042689, P30AR042689]; PHS HHS [A107512, A13154] NR 33 TC 36 Z9 36 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2004 VL 24 IS 6 BP 2237 EP 2242 DI 10.1128/MCB.24.6.2237-2242.2004 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 801MM UT WOS:000220100000003 PM 14993263 ER PT J AU Dodge, JE Kang, YK Beppu, H Lei, H Li, E AF Dodge, JE Kang, YK Beppu, H Lei, H Li, E TI Histone H3-K9 methyltransferase ESET is essential for early development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA METHYLATION; H3 METHYLTRANSFERASE; TRANSCRIPTION FACTOR; MAMMALIAN DEVELOPMENT; LYSINE-9 METHYLATION; NEUROSPORA-CRASSA; GENE-EXPRESSION; MOUSE; CELLS; G9A AB Methylation of histone H3 at lysine 9 (H3-K9) mediates heterochromatin formation by forming a binding site for HP1 and also participates in silencing gene expression at euchromatic sites. ESET, G9a, SUV39-h1, SUV39-h2, and Eu-HMTase are histone methyltransferases that catalyze H3-K9 methylation in mammalian cells. Previous studies demonstrate that the SUV39-h proteins are preferentially targeted to the pericentric heterochromatin, and mice lacking both Suv39-h genes show cytogenetic abnormalities and an increased incidence of lymphoma. G9a methylates H3-K9 in euchromatin, and G9a null embryos die at 8.5 days postcoitum (dpc). G9a null embryo stem (ES) cells show altered DNA methylation in the Prader-Willi imprinted region and ectopic expression of the Mage genes. So far, an Eu-HMTase mouse knockout has not been reported. ESET catalyzes methylation of H3-K9 and localizes mainly in euchromatin. To investigate the in vivo function of Eset, we have generated an allele that lacks the entire pre- and post-SET domains and that expresses lacZ under the endogenous regulation of the Eset gene. We found that zygotic Eset expression begins at the blastocyst stage and is ubiquitous during postimplantation mouse development, while the maternal Eset transcripts are present in oocytes and persist throughout preimplantation development. The homozygous mutations of Eset resulted in peri-implantation lethality between 3.5 and 5.5 dpc. Blastocysts null for Eset were recovered but in less than Mendelian ratios. Upon culturing, 18 of 24 Eset(-/-) blastocysts showed defective growth of the inner cell mass and, in contrast to the similar to65% recovery of wild-type and Eset(-/-) ES cells, no Eset(-/-) ES cell lines were obtained. Global H3-K9 trimethylation and DNA methylation at IAP repeats in Eset(-/-) blastocyst outgrowths were not dramatically altered. Together, these results suggest that Eset is required for peri-implantation development and the survival of ES cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Korea Res Inst Biosci, Lab Dev & Differentat, Taejon 305600, South Korea. RP Li, E (reprint author), Novartis Inst Biomed Res, 100 Technol Sq,Rm 6654, Cambridge, MA 02139 USA. EM en.li@pharma.novartis.com FU NCI NIH HHS [CA82389, R01 CA082389]; NIGMS NIH HHS [GM52106] NR 32 TC 191 Z9 196 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2004 VL 24 IS 6 BP 2478 EP 2486 DI 10.1128/MCB.24.6.2478-2486.2004 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 801MM UT WOS:000220100000025 PM 14993285 ER PT J AU Carey, JL Sasur, LM Kawakubo, H Gupta, V Christian, B Bailey, PM Maheswaran, S AF Carey, JL Sasur, LM Kawakubo, H Gupta, V Christian, B Bailey, PM Maheswaran, S TI Mutually antagonistic effects of androgen and activin in the regulation of prostate cancer cell growth SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FACTOR-BETA; SIGNAL-TRANSDUCTION; TGF-BETA; MESSENGER-RNAS; SMAD PROTEINS; CYCLE ARREST; B-CELLS; APOPTOSIS; EXPRESSION; RECEPTOR AB Activin, a member of the TGFbeta superfamily, is expressed in the prostate and inhibits growth. We demonstrate that the effects of activin and androgen on regulation of prostate cancer cell growth are mutually antagonistic. In the absence of androgen, activin induced apoptosis in the androgen-dependent human prostate cancer cell line LNCaP, an effect suppressed by androgen administration. Although activin by itself did not alter the cell cycle distribution, it potently suppressed androgen-induced progression of cells into S-phase of the cell cycle and thus inhibited androgen-stimulated growth of LNCaP cells. Expression changes in cell cycle regulatory proteins such as Rb, E2F-1, and p27 demonstrated a strong correlation with the mutually antagonistic growth regulatory effects of activin and androgen. The inhibitory effect of activin on growth was independent of serine, serine, valine, serine motif phosphorylation of Smad3. Despite their antagonistic effect on growth, activin and androgen costimulated the expression of prostate-specific antigen through a Smad3-mediated mechanism. These observations indicate the existence of a complex cross talk between activin and androgen signaling in regulation of gene expression and growth of the prostate. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. FU NCI NIH HHS [CA89138-01A1] NR 50 TC 17 Z9 18 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR 1 PY 2004 VL 18 IS 3 BP 696 EP 707 DI 10.1210/me.2003-0360 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779LR UT WOS:000189299100017 PM 14684851 ER PT J AU Fearing, MK Levy, HL Wilkins-Haug, LE Larson, C Shih, VE AF Fearing, MK Levy, HL Wilkins-Haug, LE Larson, C Shih, VE TI Maternal liver diseases in the pregnancies of infants with the spectrum of fatty acid oxidation defects compared to matched population controls. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2004) CY MAR 07-10, 2004 CL Orlando, FL SP Soc Inherited Metabolic Disorders C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp Boston, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. New England Newborn Screening Program, Boston, MA USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2004 VL 81 IS 3 BP 161 EP 161 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 778MB UT WOS:000189244400015 ER PT J AU Tan, WH Eichler, FS Hoda, S Lee, MS Grant, PE Krishnamoorthy, KS Shih, VE AF Tan, WH Eichler, FS Hoda, S Lee, MS Grant, PE Krishnamoorthy, KS Shih, VE TI Isolated sulfite oxidase deficiency-report of a case in a newborn and review of the literature. SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT Meeting of the Society-for-Inherited-Metabolic-Disorders (SIMD 2004) CY MAR 07-10, 2004 CL Orlando, FL SP Soc Inherited Metabolic Disorders C1 Harvard Univ, Sch Med, Genet Training Program, Boston, MA USA. Massachusetts Gen Hosp, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Combined Med Pediat Program, Boston, MA USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2004 VL 81 IS 3 BP 181 EP 181 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 778MB UT WOS:000189244400074 ER PT J AU Echchgadda, I Song, CS Roy, AK Chatterjee, B AF Echchgadda, I Song, CS Roy, AK Chatterjee, B TI Dehydroepiandrosterone sulfotransferase is a target for transcriptional induction by the vitamin D receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN CYTOSOLIC SULFOTRANSFERASES; FARNESOID X-RECEPTOR; HYDROXYSTEROID SULFOTRANSFERASE; MOLECULAR-CLONING; GENE PROMOTER; EXPRESSION; SULFATION; METABOLISM; LIVER; PXR AB Dehydroepiandrosterone sulfotransferase (SULT2A1) is a cytosolic enzyme that mediates sulfo-conjugation of endogenous hydroxysteroids (dehydroepiandrosterone, testosterone, bile acids), and diverse xenobiotic compounds. Upon sulfonation, SULT2A1 substrates become polar and water-soluble and thus suitable for rapid excretion. SULT2A1 is abundantly expressed in the liver and intestine. Recent evidence has shown that the ligand-activated vitamin D receptor (VDR) can transcriptionally induce the xenobiotic-metabolizing cytochrome P450 enzymes. Herein, we report that VDR also targets SULT2A1 for transcriptional activation. Vitamin D stimulated endogenous SULT2A1 expression and induced transfected human, mouse, and rat SULT2A1 promoters in liver and intestinal cells upon cotransfection with VDR. An inverted repeat DNA element (IR0), located within -191 to -168 positions of mouse and rat Sult2A1, mediates VDR induction of Sult2A1. DNase1 footprinting, competition EMSA, and antibody supershift assay showed that the IR0 is a binding site for the RXR-alpha/VDR heterodimer. Point mutations within the IR0 prevented RXR/VDR binding and abolished VDR-mediated Sult2A1 induction. The IR0 element conferred VDR responsiveness on a thymidine kinase promoter. Thus, VDR-mediated nuclear signaling may be important in the phase II metabolism involving Sult2A1. The rodent Sult2A1 gene is also induced by the farnesoid X receptor (FXR) and pregnane X receptor (PXR) through the same IR0. In competition transfections, FXR or PXR inhibited VDR induction of the IR0. Competitive functional interactions among VDR, PXR, and FXR suggest that the intracellular hormonal and metabolic milieu may determine the extent to which a specific nuclear receptor pathway would influence steroid/xenobiotic metabolism using dehydroepiandrosterone sulfotransferase. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Struct & Cellular Biol, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM chatterjee@uthscsa.edu FU NIA NIH HHS [T32-AG00165] NR 40 TC 101 Z9 104 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR 1 PY 2004 VL 65 IS 3 BP 720 EP 729 DI 10.1124/mol.65.3.720 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 775TX UT WOS:000189077700028 PM 14978251 ER PT J AU Grandi, P Wang, S Schuback, D Krasnykh, V Spear, M Curiel, DT Manservigi, R Breakefield, XO AF Grandi, P Wang, S Schuback, D Krasnykh, V Spear, M Curiel, DT Manservigi, R Breakefield, XO TI HSV-1 virions engineered for specific binding to cell surface receptors SO MOLECULAR THERAPY LA English DT Article DE virus entry; HSV receptors; targeting; virion envelope; heparan sulfate; gene therapy; HSV-1 glycoproteins ID HERPES-SIMPLEX-VIRUS; COMPLEMENT COMPONENT C3B; HEPARAN-SULFATE; GLYCOPROTEIN-C; CONFERS SUSCEPTIBILITY; ADENOVIRAL VECTORS; PSEUDORABIES VIRUS; GENE-TRANSFER; ENTRY; TYPE-1 AB Expression of specific peptide epitopes on the surface of virions has significant potential for studying viral biology and designing vectors for targeted gene therapy. In this study, an HSV-1 amplicon plasmid expressing a modified glycoprotein C (gC), in which the heparan sulfate binding domain was replaced with a His-tag, was used in generating HSV-1 virions. Western blot analysis demonstrated the presence of modified gC in the purified virions. The amplicon vectors were packaged using a gC(-), lacZ(+) helper virus to generate a mixture of high-titer helper virus (lacZ(+)) and amplicon vectors (GFP(+)), which expressed modified gC in the virion envelope. His-tagged virions bound to 293 6H cells expressing a cell surface pseudo-His-tag receptor four-fold more efficiently than to parental 293 cells and also proved more effective than wild-type virus in binding to both cell types. Binding resulted in productive infection by the modified virions with expression of reporter genes and cytopathic effect comparable to those of wild-type virions. Thus, not only can HSV-1 tropism be manipulated to recognize a non-herpes simplex binding receptor, but it is also possible to increase the infective capacity of the vectors beyond that of the wild-type virus via specific ligand receptor combinations. C1 Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Univ Alabama, Dept Surg, Dept Pathol,Dept Med, Div Human Gene Therapy, Birmingham, AL 35394 USA. Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35394 USA. Univ Calif San Diego, Ctr Canc, Gene Therapy Program, San Diego, CA 92103 USA. Univ Ferrara, Microbiol Sect, Dept Expt & Diagnost Med, I-44100 Ferrara, Italy. RP Wang, S (reprint author), Massachusetts Gen Hosp E, Dept Neurol, CNY 6205,Bldg 149,13th St, Charlestown, MA 02129 USA. EM swang@helix.mgh.harvard.edu FU NCI NIH HHS [P50 CA89019, R01CA86881]; NINDS NIH HHS [NS28384, NS37409] NR 62 TC 34 Z9 36 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2004 VL 9 IS 3 BP 419 EP 427 DI 10.1016/j.ymthe.2003.12.010 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 802NL UT WOS:000220170100018 PM 15006609 ER PT J AU Bennekov, T Spector, D Langhoff, E AF Bennekov, T Spector, D Langhoff, E TI Induction of immunity against human cytomegalovirus SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE cytomegalovirus; vaccine; immunity; gene transduction; dendritic cells ID BONE-MARROW TRANSPLANT; T-LYMPHOCYTE RESPONSES; DENDRITIC CELLS; IN-VIVO; GENE-THERAPY; RECOMBINANT ADENOVIRUSES; GANCICLOVIR PROPHYLAXIS; SURFACE EXPRESSION; CELLULAR-IMMUNITY; VIRUS PNEUMONIA AB Most healthy individuals have been exposed to human cytomegalovirus (HCMV) and harbor the virus in a dormant form. However, in situations of immune compromise, HCMV infection is associated with high mortality rates in recipients of bone marrow transplants and with significant morbidity in recipients of solid organ transplants. Conventional vaccination with attenuated HCMV or HCMV proteins fails to prime protective immune responses, presumably because the antigens fail to be presented effectively in vivo. Dendritic cells (DC) are professional antigen-presenting cells that can be genetically engineered to direct their ability to induce immune responses toward immunodominant HCMV antigens. DC are a distinct lineage of leukocytes whose function is most notable for their ability to form clusters with T cells and stimulate vigorous cytotoxic T lymphocyte responses. We hypothesize that in this capacity, DC engineered to express HCMV antigens are uniquely positioned to control immunity against HCMV. C1 Bronx Vet Adm Med Ctr, Nephrol Sect, Bronx, NY 10468 USA. Penn State Univ, Dept Microbiol & Immunol, Hershey, PA USA. State Serum Inst, Vaccine Sect, Copenhagen, Denmark. Mt Sinai Med Ctr, Div Nephrol, New York, NY 10029 USA. RP Langhoff, E (reprint author), Bronx Vet Adm Med Ctr, Nephrol Sect, Room 9C-11F,120 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Erik.Langhoff@med.va.gov FU NIAID NIH HHS [AI28734] NR 73 TC 11 Z9 13 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAR PY 2004 VL 71 IS 2 BP 86 EP 93 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 802IM UT WOS:000220157200002 PM 15029400 ER PT J AU Stegmaier, K Ross, KN Colavito, SA O'Malley, S Stockwell, BR Golub, TR AF Stegmaier, K Ross, KN Colavito, SA O'Malley, S Stockwell, BR Golub, TR TI Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation SO NATURE GENETICS LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; SMALL-MOLECULE INHIBITORS; TRANS-RETINOIC ACID; GROWTH-INHIBITION; CELLS; HL-60; MECHANISM; IDENTIFICATION; METHOTREXATE; DISCOVERY AB Chemical genomics involves generating large collections of small molecules and using them to modulate cellular states. Despite recent progress in the systematic synthesis of structurally diverse compounds, their use in screens of cellular circuitry is still an ad hoc process(1-4). Here, we outline a general, efficient approach called gene expression based high-throughput screening (GE-HTS) in which a gene expression signature is used as a surrogate for cellular states, and we describe its application in a particular setting: the identification of compounds that induce the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature and, furthermore, yielded functional evidence of bona fide differentiation. The results indicate that GE-HTS may be a powerful, general approach for chemical screening. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Golub, TR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM golub@broad.mit.edu NR 30 TC 163 Z9 175 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2004 VL 36 IS 3 BP 257 EP 263 DI 10.1038/ng1305 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 778PR UT WOS:000189250400014 PM 14770183 ER PT J AU van den Brink, GR Bleuming, SA Hardwick, JCH Schepman, BL Offerhaus, GJ Keller, JJ Nielsen, C Gaffield, W van Deventer, SJH Roberts, DJ Peppelenbosch, MP AF van den Brink, GR Bleuming, SA Hardwick, JCH Schepman, BL Offerhaus, GJ Keller, JJ Nielsen, C Gaffield, W van Deventer, SJH Roberts, DJ Peppelenbosch, MP TI Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation SO NATURE GENETICS LA English DT Article ID INTESTINAL TREFOIL FACTOR; COLORECTAL-CANCER; EXPRESSION; INHIBITION; CARCINOMA; BUTYRATE; COMPLEX; CULTURE; GROWTH; VILLIN AB Wnt signaling defines the colonic epithelial progenitor cell phenotype(1), and mutations in the gene adenomatous polyposis coli (APC) that activate the Wnt pathway cause the familial adenomatous polyposis coli (FAP) syndrome and most sporadic colon cancers(2). The mechanisms that regulate the transition of epithelial precursor cells into their differentiated derivatives are poorly characterized. We report that Indian hedgehog (Ihh) is expressed by mature colonocytes and regulates their differentiation in vitro and in vivo. Hedgehog (Hh) signaling restricts the expression of Wnt targets to the base of the colonic crypt in vivo, and transfection of Ihh into colon cancer cells leads to a downregulation of both components of the nuclear TCF4-beta-catenin complex and abrogates endogenous Wnt signaling in vitro. In turn, expression of Ihh is downregulated in polyps of individuals with FAP and expression of doxycycline-inducible dominant negative TCF4 (dnTCF4) restores Ihh expression in APC mutant DLD-1 colon cancer cells. These data identify a new Wnt-Hh axis in colonic epithelial renewal. C1 Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. ARS, Western Reg Res Ctr, USDA, Albany, CA USA. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. RP van den Brink, GR (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM g.r.vandenbrink@amc.uva.nl OI Hardwick, James/0000-0002-9575-5099 NR 21 TC 237 Z9 243 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2004 VL 36 IS 3 BP 277 EP 282 DI 10.1038/ng1304 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 778PR UT WOS:000189250400017 PM 14770182 ER PT J AU Burton, DR Desrosiers, RC Doms, RW Koff, WC Kwong, PD Moore, JP Nabel, GJ Sodroski, J Wilson, IA Wyatt, RT AF Burton, DR Desrosiers, RC Doms, RW Koff, WC Kwong, PD Moore, JP Nabel, GJ Sodroski, J Wilson, IA Wyatt, RT TI HIV vaccine design and the neutralizing antibody problem SO NATURE IMMUNOLOGY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; TYPE-1; BINDING; GP120; SELECTIVITY; RECOGNITION; ANTIGENS; REGION; GP41 AB Eliciting broadly neutralizing antibodies to human immunodeficiency virus could bring closer the goal of a successful AIDS vaccine. Here the International AIDS Vaccine Initiative Neutralizing Antibody Consortium discusses current approaches to overcome the problems faced. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Microbiol, Southborough, MA 01772 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Int AIDS Vaccine Initiat, New York, NY USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Ctr, Dept Microbiol & Immunol, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM burton@scripps.edu NR 21 TC 569 Z9 591 U1 5 U2 42 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2004 VL 5 IS 3 BP 233 EP 236 DI 10.1038/ni0304-233 PG 4 WC Immunology SC Immunology GA 779ZV UT WOS:000189344600002 PM 14985706 ER PT J AU Heissmeyer, V Macian, F Im, SH Varma, R Feske, S Venuprasad, K Gu, H Liu, YC Dustin, ML Rao, A AF Heissmeyer, V Macian, F Im, SH Varma, R Feske, S Venuprasad, K Gu, H Liu, YC Dustin, ML Rao, A TI Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SYNAPSE; CBL-B; GENE-TRANSCRIPTION; DOWN-REGULATION; KINASE-C; IN-VIVO; ACTIVATION; RECEPTOR; ANTIGEN; RAP1 AB Sustained calcium signaling induces a state of anergy or antigen unresponsiveness in T cells, mediated through calcineurin and the transcription factor NFAT. We show here that Ca2+-induced anergy is a multistep program that is implemented at least partly through proteolytic degradation of specific signaling proteins. Calcineurin increased mRNA and protein of the E3 ubiquitin ligases Itch, Cbl-b and GRAIL and induced expression of Tsg101, the ubiquitin-binding component of the ESCRT-1 endosomal sorting complex. Subsequent stimulation or homotypic cell adhesion promoted membrane translocation of Itch and the related protein Nedd4, resulting in degradation of two key signaling proteins, PKC-theta and PLC-gamma1. T cells from Itch- and Cbl-b-deficient mice were resistant to anergy induction. Anergic T cells showed impaired calcium mobilization after TCR triggering and were unable to maintain a mature immunological synapse, instead showing late disorganization of the outer ring containing lymphocyte function-associated antigen 1. Our results define a complex molecular program that links gene transcription induced by calcium and calcineurin to a paradoxical impairment of signal transduction in anergic T cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NYU, Sch Med, Program Mol Pathogenesis, New York, NY 10016 USA. NYU, Sch Med, Dept Pathol, Skirball Inst Mol Med, New York, NY 10016 USA. La Jolla Inst Allergy & Immunol, Div Cell Biol, San Diego, CA 92121 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu RI Varma, Rajat/I-1209-2012; Im, Sin-Hyeog/E-6811-2013; OI Varma, Rajat/0000-0001-5131-0402; Feske, Stefan/0000-0001-5431-8178; Im, Sin-Hyeog/0000-0002-3173-1856; Macian, Fernando/0000-0003-2666-035X; Dustin, Michael/0000-0003-4983-6389 FU NIAID NIH HHS [AI 43542, R01 AI 40127, R01 AI 48213, R01 AI 50280, R21 AI 48542]; NICHD NIH HHS [R03 HD 39685] NR 51 TC 351 Z9 365 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2004 VL 5 IS 3 BP 255 EP 265 DI 10.1038/ni1047 PG 11 WC Immunology SC Immunology GA 779ZV UT WOS:000189344600008 PM 14973438 ER PT J AU Casola, S Otipoby, KL Alimzhanov, M Humme, S Uyttersprot, N Kutok, JL Carroll, MC Rajewsky, K AF Casola, S Otipoby, KL Alimzhanov, M Humme, S Uyttersprot, N Kutok, JL Carroll, MC Rajewsky, K TI B cell receptor signal strength determines B cell fate SO NATURE IMMUNOLOGY LA English DT Article ID SPLENIC MARGINAL ZONE; MEMBRANE-PROTEIN 2A; BARR-VIRUS LMP2A; POSITIVE SELECTION; ANTIGEN RECEPTOR; B-1 CELLS; SURFACE-IMMUNOGLOBULIN; GERMINAL-CENTERS; IMMUNE-RESPONSES; ACTIVATION MOTIF AB B cell receptor (BCR)-mediated antigen recognition is thought to regulate B cell differentiation. BCR signal strength may also influence B cell fate decisions. Here, we used the Epstein-Barr virus protein LMP2A as a constitutively active BCR surrogate to study the contribution of BCR signal strength in B cell differentiation. Mice carrying a targeted replacement of Igh by LMP2A leading to high or low expression of the LMP2A protein developed B-1 or follicular and marginal zone B cells, respectively. These data indicate that BCR signal strength, rather than antigen specificity, determines mature B cell fate. Furthermore, spontaneous germinal centers developed in gut-associated lymphoid tissue of LMP2A mice, indicating that microbial antigens can promote germinal centers independently of BCR-mediated antigen recognition. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu FU NCI NIH HHS [CA 098285-01A1, CA 92625] NR 59 TC 333 Z9 341 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2004 VL 5 IS 3 BP 317 EP 327 DI 10.1038/ni1036 PG 11 WC Immunology SC Immunology GA 779ZV UT WOS:000189344600015 PM 14758357 ER PT J AU Noguchi, H Matsushita, M Okitsu, T Moriwaki, A Tomizawa, K Kang, SY Li, ST Kobayashi, N Matsumoto, S Tanaka, K Tanaka, N Matsui, H AF Noguchi, H Matsushita, M Okitsu, T Moriwaki, A Tomizawa, K Kang, SY Li, ST Kobayashi, N Matsumoto, S Tanaka, K Tanaka, N Matsui, H TI A new cell-permeable peptide allows successful allogeneic islet transplantation in mice SO NATURE MEDICINE LA English DT Article ID VIVO PROTEIN TRANSDUCTION; CYCLOSPORINE-A; DELIVERY; MECHANISM; FK506 AB Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system(1,2). This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically. C1 Okayama Univ, Grad Sch Med & Dent, Dept Physiol, Okayama 7008558, Japan. Okayama Univ, Grad Sch Med & Dent, Dept Gastroenterol Surg Transplant & Surg Oncol, Okayama 7008558, Japan. Kyoto Univ Hosp, Dept Transplantat & Immunol, Sakyo Ku, Kyoto 6068507, Japan. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Okayama Univ, Grad Sch Med & Dent, Japan Sci & Technol Corp, Off Technol,Preventure Program, Okayama 7008558, Japan. RP Matsushita, M (reprint author), Okayama Univ, Grad Sch Med & Dent, Dept Physiol, 2-5-1 Shikata Cho, Okayama 7008558, Japan. EM masayuki@cc.okayama-u.ac.jp RI Tomizawa, Kazuhito/F-2405-2015; OI Tomizawa, Kazuhito/0000-0002-5663-2627; Li, Sheng Tian/0000-0002-2836-3802 NR 21 TC 171 Z9 176 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2004 VL 10 IS 3 BP 305 EP 309 DI 10.1038/nm994 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 779LH UT WOS:000189297700044 PM 14770176 ER PT J AU Messerli, SM Prabhakar, S Tang, Y Shah, K Cortes, ML Murthy, V Weissleder, R Breakefield, XO Tung, CH AF Messerli, SM Prabhakar, S Tang, Y Shah, K Cortes, ML Murthy, V Weissleder, R Breakefield, XO Tung, CH TI A novel method for imaging apoptosis using a caspase-1 near-infrared fluorescent probe SO NEOPLASIA LA English DT Article DE caspase-1; near-infrared fluorescence (NIRF); apoptosis; brain tumors; HSV ID HUMAN PROSTATE-CANCER; IN-VIVO; CELL-DEATH; NITRIC-OXIDE; IL-1-BETA-CONVERTING ENZYME; TISSUE-SECTIONS; TUNEL METHOD; PROTEASE; EXPRESSION; ACTIVATION AB Here we describe a novel method for imaging apoptosis in cells using a near-infrared fluorescent (NRF) probe selective for caspase-1 (interleukin 1beta-converting enzyme, ICE). This biocompatible, optically quenched ICE-NIRF probe incorporates a peptide substrate, which can be selectively cleaved by caspase-1, resulting in the release of fluorescence signal. The specificity of this probe for caspase-1 is supported by various lines of evidence: 1) activation by purified caspase-1, but not another caspase in vitro; 2) activation of the probe by infection of cells with a herpes simplex virus amplicon vector (HGC-ICE-lacZ) expressing a catalytically active caspase-1-lacZ fusion protein; 3) inhibition of HGC-ICE-lacZ vector-induced activation of the probe by coincubation with the caspase-1 inhibitor YVAD-cmk, but not with a caspase-3 inhibitor; and 4) activation of the probe following standard methods of inducing apoptosis with staurosporine, ganciclovir, or ionizing radiation in culture. These results indicate that this novel ICE-NIRF probe can be used in monitoring endogenous and vector-expressed caspase-1 activity in cells. Furthermore, tumor implant experiments indicate that this ICE-NIRF probe can be used to detect caspase-1 activity in living animals. This novel ICE-NIRF probe should prove useful in monitoring endogenous and vector-expressed caspase-1 activity, and potentially apoptosis in cell culture and in vivo. C1 Harvard Univ, Mol Neurogenet Unit, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02129 USA. Harvard Univ, Mol Neurogenet Unit, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. RP Breakefield, XO (reprint author), Harvard Univ, Mol Neurogenet Unit, Dept Neurol, Massachusetts Gen Hosp,Med Sch, Bldg 149,13th St, Boston, MA 02129 USA. EM breakefield@hms.haward.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA086355, P50-CA86355, R24 CA092782, R24-CA92782, R33 CA088365, R33-CA88365] NR 52 TC 74 Z9 81 U1 1 U2 16 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAR-APR PY 2004 VL 6 IS 2 BP 95 EP 105 DI 10.1593/neo.03214 PG 11 WC Oncology SC Oncology GA 816TY UT WOS:000221133400001 PM 15140398 ER PT J AU Reger, MA Henderson, ST Hale, C Cholerton, B Baker, LD Watson, GS Hyde, K Chapman, D Craft, S AF Reger, MA Henderson, ST Hale, C Cholerton, B Baker, LD Watson, GS Hyde, K Chapman, D Craft, S TI Effects of beta-hydroxybutyrate on cognition in memory-impaired adults SO NEUROBIOLOGY OF AGING LA English DT Article DE beta-hydroxybutyrate; ketone bodies; Alzheimer's disease; mild cognitive impairment; APOE; cognition; neuropsychology ID ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; SENILE DEMENTIA; BRAIN; HYPOGLYCEMIA; RESPONSES AB Glucose is the brain's principal energy substrate. In Alzheimer's disease (AD), there appears to be a pathological decrease in the brain's ability to use glucose. Neurobiological evidence suggests that ketone bodies are, an effective alternative energy substrate for the brain. Elevation of plasma ketone body levels. through an oral dose of medium chain triglycerides (MCTs) may improve cognitive functioning in older adults with memory disorders. On separate days, 20 subjects with AD or niild cognitive impairment consumed a drink containing emulsified MCTs or placebo: Significant increases in levels of the ketone body beta-hydroxybutyrate (beta-OHB) were observed 90 min after treatment (P = 0.007) when cognitive tests were administered. beta-OHB elevations were moderated by apolipoprotein E (APOE) genotype (P = 0.036). For epsilon4+ subjects, beta-OHB levels continued to rise between the 90 and 120 min blood draws in the treatment condition, while the p-OHB levels of epsilon4- subjects held constant (P < 0.009). On cognitive testing, MCT treatment facilitated performance on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) for epsilon4- subjects, but not for epsilon4+ subjects (P = 0.04). Higher ketone values were associated with greater improvement in paragraph recall with MCT treatment relative to placebo across all subjects (P = 0.02). Additional research is warranted to determine the therapeutic benefits of MCTs for patients with AD and how APOE-epsilon4 status may mediate p-OHB efficacy. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Accera Inc, Aurora, CO 80010 USA. Univ Puget Sound, Dept Psychol, Tacoma, WA 98416 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way,S-182-GRECC, Seattle, WA 98108 USA. EM scraft@u.washington.edu NR 19 TC 134 Z9 135 U1 3 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2004 VL 25 IS 3 BP 311 EP 314 DI 10.1016/S0197-4580(03)00087-3 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 778FV UT WOS:000189229600006 PM 15123336 ER PT J AU Mesches, MH Gemma, C Veng, LM Allgeier, C Young, DA Browning, MD Bickford, PC AF Mesches, MH Gemma, C Veng, LM Allgeier, C Young, DA Browning, MD Bickford, PC TI Sulindac improves memory and increases NMDA receptor subunits in aged Fischer 344 rats SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; memory; nonsteroidal anti-inflammatory drug; NSAID; N-methyl-D-aspartate receptor; NMDA-R; cytokine; neurodegeneration; water maze; fear conditioning; hippocampus; interleukin 1 beta ID LONG-TERM POTENTIATION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NEURONAL SIGNAL-TRANSDUCTION; PPAR-GAMMA AGONISTS; ALZHEIMERS-DISEASE; DIETARY SUPPLEMENTATION; BEHAVIORAL DEFICITS; CHRONIC NEUROINFLAMMATION; INFLAMMATORY MECHANISMS; SPATIAL MEMORY AB Inflammatory processes in the central nervous system are thought to contribute to Alzheimer's disease (AD). Chronic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of Alzheimer's disease. There are very few studies, however, on the cognitive impact of chronic NSAID administration. The N-methyl-D-aspartate (NMDA) receptor is implicated in learning and memory, and age-related decreases in the NMDA NR2B subunit correlate with memory deficits. Sulindac, an NSAID that is a nonselective cyclooxygenase (COX) inhibitor was chronically administered to aged Fischer 344 rats for 2 months. Sulindac, but not its non-COX active metabolite, attenuated age-related deficits in learning and memory as assessed in the radial arm water maze and contextual fear conditioning tasks. Sulindac treatment also attenuated an age-related decrease in the NR1 and NR2B NMDA receptor subunits and prevented an age-related increase in the pro-inflammatory cytokine, interleukin 1beta (IL-1beta), in the hippocampus. These findings support the inflammation hypothesis of aging and have important implications for potential cognitive enhancing effects of NSAIDs in the elderly. (C) 2003 Elsevier Inc. All rights reserved. C1 Denver VA Med Ctr, Med Res Serv 151, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. James A Haley Vet Adm Med Ctr, Res Serv, Tampa, FL 33620 USA. USFCOM, Dept Neurosurg, Ctr Aging & Brain Repair, Tampa, FL USA. RP Mesches, MH (reprint author), Denver VA Med Ctr, Med Res Serv 151, 1055 Clermont St, Denver, CO 80220 USA. EM michael.mesches@uchsc.edu RI Bickford, Paula/J-5970-2012; OI Bickford, Paula/0000-0001-9657-7725; Gemma, Carmelina/0000-0002-4480-0056 FU NIA NIH HHS [AG00961, AG04418] NR 68 TC 57 Z9 61 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR PY 2004 VL 25 IS 3 BP 315 EP 324 DI 10.1016/S0197-4580(03)00116-7 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 778FV UT WOS:000189229600007 PM 15123337 ER PT J AU Brown, AM Gordon, D Lee, H Caudy, M Haroutunian, V Blass, JP AF Brown, AM Gordon, D Lee, H Caudy, M Haroutunian, V Blass, JP TI Substantial linkage disequilibrium across the dihydrolipoyl succinyltransferase gene region without Alzheimer's disease association SO NEUROCHEMICAL RESEARCH LA English DT Article DE energy metabolism; mitochondria; gene; Alzheimer's disease; polymorphism ID KETOGLUTARATE DEHYDROGENASE COMPLEX; HARDY-WEINBERG PROPORTIONS; APOLIPOPROTEIN-E; DLST GENE; TYPE-4 ALLELE; FREQUENCY; MUTATIONS; GENOTYPE; TESTS; RISK AB Association of the candidate gene DLST with late-onset Alzheimer's disease (LOAD) risk has been suggested on the basis of case-control studies. This gene, located on chromosome 24q24.3, encodes a subunit of a mitochondrial component known to be defective in AD, the alpha-ketoglutarate dehydrogenase complex. Positive reports have correlated different DLST alleles with LOAD, whereas other groups have failed to find any significant association. We therefore reexamined the association of DLST and LOAD in a more ethnically homogeneous series using three additional single nucleotide polymorphisms (SNP) located within or closely flanking either end of the DLST gene. Pairwise analysis of these SNPs indicated there was strong linkage disequilibrium across the DLST locus. Analysis of complex genotypes or haplotypes based upon all five SNP loci failed to identify a LOAD risk allele, suggesting that further studies of DLST in relation to AD are not warranted. C1 Burke Med Res Inst, Dementia Res Serv, White Plains, NY 10605 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Brown, AM (reprint author), Burke Med Res Inst, Dementia Res Serv, 785 Mamaroneck Ave, White Plains, NY 10605 USA. EM ambrown@med.cornell.edu FU NHGRI NIH HHS [K01-HG00055]; NIA NIH HHS [AG14930, P01-AG02219]; NIMH NIH HHS [MH44292] NR 40 TC 4 Z9 5 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAR PY 2004 VL 29 IS 3 BP 629 EP 635 DI 10.1023/B:NERE.0000014833.54481.1d PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 770ZB UT WOS:000188760300016 PM 15038610 ER PT J AU Manoach, DS White, NS Lindgren, KA Heckers, S Coleman, MJ Dubal, S Holzman, PS AF Manoach, DS White, NS Lindgren, KA Heckers, S Coleman, MJ Dubal, S Holzman, PS TI Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory SO NEUROIMAGE LA English DT Article DE hemispheric specialization; lateral prefrontal cortex; strategic processing; working memory ID EVENT-RELATED FMRI; HUMAN FRONTAL-CORTEX; FUNCTIONAL-ORGANIZATION; EXECUTIVE CONTROL; TASK; MAINTENANCE; PERFORMANCE; REGIONS; ROLES; ASSOCIATION AB Objective: We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. Methods: We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. Results: compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. Conclusions: These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 36 1st Ave,Room 420,Charlestown Navy Yard, Charlestown, MA 02129 USA. EM dara@nmr.mgh.harvard.edu RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NCRR NIH HHS [P41 RR14075]; NIMH NIH HHS [P01 MH31154, K23 MH01829, R01 MH31340] NR 44 TC 30 Z9 31 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2004 VL 21 IS 3 BP 894 EP 903 DI 10.1016/j.neuroimage.2003.10.025 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 802FH UT WOS:000220148900010 PM 15006656 ER PT J AU Katz, MM Tekell, JL Bowden, CL Brannan, S Houston, JP Berman, N Frazer, A AF Katz, MM Tekell, JL Bowden, CL Brannan, S Houston, JP Berman, N Frazer, A TI Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE onset of antidepressant effects; antidepressants; desipramine; paroxetine; unipolar depression; norepinephrine; serotonin ID GENERALIZED ANXIETY DISORDER; LOCUS-COERULEUS NEURONS; TRUE DRUG RESPONSE; 5-HYDROXYINDOLEACETIC ACID; VIDEO METHODOLOGY; EARLY IMPROVEMENT; MAJOR DEPRESSION; PATTERN-ANALYSIS; PAROXETINE; SEROTONIN AB This study was aimed at resolving the time course of clinical action of antidepressants (ADs) and the type of early behavioral changes that precede recovery in treatment-responsive depressed patients. The first goal was to identify, during the first 2 weeks of treatment, the onset of clinical actions of the selective serotonin reuptake inhibitor (SSRI), paroxetine, and the selective noradrenergic reuptake inhibitor, desipramine (DMI). The second aim was to test the hypothesis that the two pharmacologic subtypes would induce different early behavioral changes in treatment-responsive patients. The design was a randomized, parallel group, placebo-controlled, double-blind study for 6 weeks of treatment following a 1-week washout period. The study utilized measures of the major behavioral components of the depressive disorder as well as overall severity. The results indicated that the onset of clinical actions of DMI ranged from 3 to 13 days, averaged 13 days for paroxetine, and was 16-42 days for placebo. Furthermore, as hypothesized, the different types of ADs initially impacted different behavioral aspects of the disorder. After I week of treatment, DMI produced greater reductions in motor retardation and depressed mood than did paroxetine and placebo, and this difference persisted at the second week of treatment. Early improvement in depressed mood-motor retardation differentiated patients who responded to DMI after 6 weeks of treatment from those that did not. Paroxetine initially reduced anxiety more in responders than in nonresponders, and by the second week, significantly improved depressed mood and distressed expression in responders to a greater extent. Depressed patients who responded to placebo showed no consistent early pattern of behavior improvement. Early drug-specific behavioral changes were highly predictive of ultimate clinical response to the different ADs, results that could eventually be applied directly to clinical practice. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, SW Med Ctr, Dallas VA Med CTr, Dept Psychiat, Dallas, TX USA. Cyberonics, Houston, TX USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Frazer, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr,MSC 7764, San Antonio, TX 78284 USA. EM frazer@uthscsa.edu NR 68 TC 143 Z9 147 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2004 VL 29 IS 3 BP 566 EP 579 DI 10.1038/sj.npp.1300341 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 800FE UT WOS:000220013500015 PM 14627997 ER PT J AU Smith, ER Butler, WE Barker, FG AF Smith, ER Butler, WE Barker, FG TI Craniotomy for resection of pediatric brain tumors in the United States, 1988 to 2000: Effects of provider caseloads and progressive centralization and specialization of care SO NEUROSURGERY LA English DT Article DE centralization; craniotomy; mortality rate; pediatric brain neoplasms; specialization; volume-outcome relationship ID IN-HOSPITAL MORTALITY; CEREBROSPINAL-FLUID SHUNT; NEW-YORK-STATE; SURGEON VOLUME; NEUROSURGICAL SUBSPECIALIZATION; OPERATIVE MORTALITY; CARDIAC-SURGERY; CANCER-PATIENTS; REGIONALIZATION; CHILDREN AB OBJECTIVE: Large provider caseloads are associated with better patient outcomes after many complex surgical procedures. Mortality rates for pediatric brain tumor surgery in various practice settings have not been described. We used a national hospital discharge database to study the volume-outcome relationship for craniotomy performed for pediatric brain tumor resection, as well as trends toward centralization and specialization. METHODS: We conducted a cross sectional and longitudinal cohort study using Nationwide Inpatient Sample data for 1988 to 2000 (Agency for Healthcare Research and Quality, Rockville, MD). Multivariate analyses adjusted for age, sex, geographic region, admission type (emergency, urgent, or elective), tumor location, and malignancy. RESULTS: We analyzed 4712 admissions (329 hospitals, 480 identified surgeons) for pediatric brain tumor craniotomy. The in-hospital mortality rate was 1.6% and decreased from 2.7% (in 1988-1990) to 1.2% (in 1997-2000) during the study period. On a per-patient basis, median annual caseloads were 11 for hospitals (range, 1-59 cases) and 6 for surgeons (range, 1-32 cases). In multivariate analyses, the mortality rate was significantly lower at high-volume hospitals than at low-volume hospitals (odds ratio, 0.52 for 10-fold larger caseload; 95% confidence interval, 0.28-0.94; P = 0.03). The mortality rate was 2.3% at the lowest-volume-quartile hospitals (4 or fewer admissions annually), compared with 1.4% at the highest-volume-quartile hospitals (more than 20 admissions annually). There was a trend toward lower mortality rates after surgery performed by high-volume surgeons (P = 0.16). Adverse hospital discharge disposition was less likely to be associated with high-volume hospitals (P < 0.001) and high-volume surgeons (P = 0.004). Length of stay and hospital charges were minimally related to hospital caseloads. Approximately 5% of United States hospitals performed pediatric brain tumor craniotomy during this period. The burden of care shifted toward large-caseload hospitals, teaching hospitals, and surgeons whose practices included predominantly pediatric patients, indicating progressive centralization and specialization. CONCLUSION: Mortality and adverse discharge disposition rates for pediatric brain tumor craniotomy were lower when the procedure was performed at high-volume hospitals and by high-volume surgeons in the United States, from 1988 to 2000. There were trends toward lower mortality rates, greater centralization of surgery, and more specialization among surgeons during this period. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 59 TC 69 Z9 70 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAR PY 2004 VL 54 IS 3 BP 553 EP 563 DI 10.1227/01.NEU.0000108421.69822.67 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 802FN UT WOS:000220149500013 PM 15028128 ER PT J AU Thio, SSC Bonventre, JV Hsu, SIH AF Thio, SSC Bonventre, JV Hsu, SIH TI The CtBP2 co-repressor is regulated by NADH-dependent dimerization and possesses a novel N-terminal repression domain SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-BINDING ACTIVITY; D-LACTATE DEHYDROGENASE; TRANSCRIPTIONAL COREPRESSOR; ACID DEHYDROGENASES; HISTONE DEACETYLASE; ADENOVIRUS E1A; PROTEIN SIR2; GENE; TRANSFORMATION; TUMORIGENESIS AB The C-terminal binding protein 2 (CtBP2) is a 48 kDa phosphoprotein reported to function as a co- repressor for a growing list of transcriptional repressors. It was recently demonstrated that CtBP is a dimeric NAD(+)-regulated d-isomer-specific 2-hydroxy acid dehydrogenase. However, the specific substrate(s) of CtBP enzymatic activity and the relationship of this activity to its co-repression function remain unknown. The ability of a human CtBP to bind and serve as a co-repressor of E1A has been shown to be regulated by nuclear NADH levels. Here we extend the functional characterization of CtBP by demonstrating that amino acid substitutions at Gly189 in the conserved NAD(+)-binding fold both abrogate the ability of CtBP2 to homodimerize and are associated with a dramatic loss of co-repressor activity. Consistent with the known enzymatic activity of CtBP2, mutations at Arg272 in the substrate-binding domain and at His321 in the catalytic domain result in significant loss of CtBP2 transcriptional co-repressor activity. High resolution serial C-terminal deletion analysis of CtBP2 also revealed a novel N-terminal repression domain that is distinct from its dehydrogenase domain. Our results suggest a model in which CtBP2 co-repressor function is regulated, at least in part, through the effect of NADH on CtBP2 homodimerization. C1 Natl Univ Singapore, Fac Med, Dept Med, Singapore 119074, Singapore. Genome Inst Singapore, Singapore 117528, Singapore. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hsu, SIH (reprint author), Natl Univ Singapore Hosp, Dept Med, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. EM mdchsus@nus.edu.sg NR 38 TC 27 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR PY 2004 VL 32 IS 5 BP 1836 EP 1847 DI 10.1093/nar/gkh344 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807FK UT WOS:000220487200031 PM 15037661 ER PT J AU Sogg, S Mori, DL AF Sogg, S Mori, DL TI The Boston interview for gastric bypass: Determining the psychological suitability of surgical candidates SO OBESITY SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-Behavioral-Medicine CY MAR 19-22, 2003 CL SALT LAKE CITY, UT SP Soc Behavioral Med DE bariatric surgery; gastric bypass; morbid obesity; psychological evaluation ID TERM FOLLOW-UP; OBESITY; SURGERY/ AB Morbid obesity is a rapidly escalating problem in the United States, one with serious health ramifications. Due to the lack of empirical support for the long-term efficacy of non-surgical interventions for obesity, gastric bypass surgery has been pursued with increasing frequency as a treatment for morbid obesity. Because surgery is a high-risk, invasive treatment option, medical, psychological and behavioral factors must be carefully considered in pre-surgical evaluations. Although psychological evaluations are requested by surgical teams, there is currently no commonly used, standardized protocol for this type of assessment. Further, there is little empirical data specifying which factors predict successful surgical outcomes. A general overview of a semi-structured interview for presurgical gastric bypass evaluation, developed by the Medical Psychology Service at the VA Boston Healthcare System, is provided in this paper. This standardized approach has many advantages: it ensures comprehensive assessment of relevant factors; it facilitates both research and training; and it facilitates patient education about the procedure. C1 Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Sogg, S (reprint author), 29 Mt Hood Rd 2, Brighton, MA 02135 USA. NR 15 TC 39 Z9 41 U1 1 U2 6 PU F D-COMMUNICATIONS INC PI TORONTO PA 3100 BAYVIEW AVE, UNIT 4, TORONTO, ONTARIO M2N 5L3, CANADA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD MAR PY 2004 VL 14 IS 3 BP 370 EP 380 DI 10.1381/096089204322917909 PG 11 WC Surgery SC Surgery GA 809XD UT WOS:000220668500014 PM 15072659 ER PT J AU Androudi, S Iaccheri, B Brazitikos, P Papadaki, T Foster, CS AF Androudi, S Iaccheri, B Brazitikos, P Papadaki, T Foster, CS TI Bilateral chronic anterior uveitis & neuroophthalmologic manifestations in a patient with Churg-Strauss syndrome: An unusual ocular presentation SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE Churg-Strauss syndrome; anterior uveitis; immunosuppressive treatment ID ALLERGIC GRANULOMATOSIS; POLYARTERITIS-NODOSA; SYSTEMIC VASCULITIS; ANGIITIS; CYCLOPHOSPHAMIDE; PSEUDOTUMOR; INVOLVEMENT AB We describe a patient with Churg-Strauss syndrome (CSS) who developed bilateral chronic anterior uveitis and neuro-ophthalmologic manifestations 20 years after the onset of asthma and sinus disease. ne patient was treated successfully with a combination of cyclophosphamide and prednisone, after other immunomodulatory strategies, aside from systemic prednisone, had failed. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Aristotle Univ Thessaloniki, GR-54006 Thessaloniki, Greece. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 18 TC 6 Z9 7 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAR PY 2004 VL 12 IS 1 BP 59 EP 63 DI 10.1076/ocii.12.1.59.28071 PG 5 WC Ophthalmology SC Ophthalmology GA 811XH UT WOS:000220804100008 PM 15209465 ER PT J AU Bellon, JR Harris, JR AF Bellon, JR Harris, JR TI The Lannin/Haffty article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BREAST-CANCER; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; LUMPECTOMY; TAMOXIFEN; THERAPY; IRRADIATION C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Bellon, JR (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2004 VL 18 IS 3 BP 286 EP + PG 2 WC Oncology SC Oncology GA 052DF UT WOS:000238210600008 ER PT J AU Smith, MR AF Smith, MR TI The Holzbeierlein/Castle/Thrasher article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID INSULIN RESISTANCE; PROSTATE-CANCER; DISEASE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Smith, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAR PY 2004 VL 18 IS 3 BP 315 EP + PG 2 WC Oncology SC Oncology GA 052DF UT WOS:000238210600012 ER PT J AU Sarna, L Brown, JK Cooley, ME Padilla, G Chernecky, C Danao, L AF Sarna, L Brown, JK Cooley, ME Padilla, G Chernecky, C Danao, L TI Comparison of health status and quality of life of women with lung cancer and their family members. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Buffalo, Sch Nursing, Buffalo, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. Med Coll Georgia, Sch Nursing, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 14 BP 382 EP 382 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400034 ER PT J AU Healey, M Vettese, M Cooley, M Epshtein, A Wu, SB AF Healey, M Vettese, M Cooley, M Epshtein, A Wu, SB TI Clinical scholar award: A mentored research program. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 26 BP 386 EP 386 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400046 ER PT J AU Sohl, L Johnson, E Ghiloni, C Woods, R Barron, AM AF Sohl, L Johnson, E Ghiloni, C Woods, R Barron, AM TI A new graduate nurse development program: Expanding, integrating, and supporting the professional development of new and experienced oncology nursing staff. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 30 BP 387 EP 387 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400050 ER PT J AU Gallagher, J Tenhover, J Joyce, E Binda, K AF Gallagher, J Tenhover, J Joyce, E Binda, K TI Complementary therapies: Knowledge, attitudes, and use among cancer center health professionals. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 79 BP 402 EP 402 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400099 ER PT J AU Barron, AM Sohl, L Johnson, E Ghiloni, C AF Barron, AM Sohl, L Johnson, E Ghiloni, C TI Initiating weekly reflective practice rounds on an inpatient oncology/bone marrow transplant unit. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 110 BP 411 EP 411 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400130 ER PT J AU Kelly, K AF Kelly, K TI The management of peripheral neuropathy (PN) associated with therapy for multiple myeloma (MM). SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 129 BP 416 EP 416 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400149 ER PT J AU Delaney, R Powell, P AF Delaney, R Powell, P TI Collaboration between head and neck multi-clinic and radiation-based nursing practice. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 161 BP 426 EP 426 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400181 ER PT J AU Dahlin, C AF Dahlin, C TI National consensus project for quality palliative carepalliative care standards. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 170 BP 428 EP 428 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400190 ER PT J AU Johnson, E Dette, EO Ghiloni, C McElhinny, M Sohl, L AF Johnson, E Dette, EO Ghiloni, C McElhinny, M Sohl, L TI Cumulative grief: A program to recognize and support staff responses to patients' deaths. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 174 BP 429 EP 430 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400194 ER PT J AU Buswell, L LaFrancesca, J AF Buswell, L LaFrancesca, J TI Collaborative development of an outpatient infusion nursing documentation tool within a shared electronic medical record (EMR) application. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 208 BP 439 EP 439 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400228 ER PT J AU Borden, C Singh, P Tracey, E AF Borden, C Singh, P Tracey, E TI Changing organizational culture by celebrating quality improvements: An institute wide approach. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 220 BP 443 EP 443 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400240 ER PT J AU Lipshires, K AF Lipshires, K TI Utilization of a downtime procedure during failure of the chemotherapy order entry (COE) system. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 223 BP 444 EP 444 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400243 ER PT J AU Ponte, PR Gross, A Kruger, N Schulte, K Jodoin, C Molina, E AF Ponte, PR Gross, A Kruger, N Schulte, K Jodoin, C Molina, E TI Improving oncology discharge process in a complex tertiary care center. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 226 BP 445 EP 445 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400246 ER PT J AU Cooley, M Rimar, J Knafl, G McCorkle, R AF Cooley, M Rimar, J Knafl, G McCorkle, R TI Health-related quality of life questionnaires as predictors of unscheduled healthcare visits in adults with cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Nursing, New Haven, CT 06536 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2004 VL 31 IS 2 MA 271 BP 458 EP 458 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 875RC UT WOS:000225438400289 ER PT J AU Mandeville, JTH Roh, JH Woog, JJ Gonnering, RS Levin, PS Mazzoli, RA Ainbinder, DJ Older, JJ Moulin, AP Kiel, R Kim, YD Dryja, TP AF Mandeville, JTH Roh, JH Woog, JJ Gonnering, RS Levin, PS Mazzoli, RA Ainbinder, DJ Older, JJ Moulin, AP Kiel, R Kim, YD Dryja, TP TI Cutaneous benign mixed tumor (Chondroid syringoma) of the eyelid: Clinical presentation and management SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID FLUID PROTEIN GCDFP-15; SWEAT GLAND TUMORS; SKIN; DIFFERENTIATION; IMMUNOHISTOCHEMISTRY; FEATURES; ECCRINE AB Purpose: To describe the clinical presentation of cutaneous benign mixed tumor of the eyelid and its management options. Methods: Periocular cases of cutaneous benign mixed tumor were gathered from members of an oculoplastics specialty Internet discussion group. A total of 9 patients are described in this retrospective, interventional case series. The, clinical presentation, histopathology, and management of these lesions is reviewed. Results: Patients were typically asymptomatic, presenting with a. slowly enlarging, nontender nodule of 2 to 8 years' duration. The lesions ranged from 4 mm to 17 mm in greatest dimension. Four of the lesions were on the eyelid margin, three in the sub-brow area of the upper eyelid, and two in the central lids. All six cases not involving the brow were fixed to the tarsus; one brow lesion was believed to be adherent to the skin. None of the lesions was associated with significant changes of the overlying epidermis, although one lesion showed overlying pigmentation. All patients underwent excisional biopsy for diagnostic or cosmetic reasons. On histopathologic examination, the tumors were biphasic, with an epithelial component exhibiting apocrine or hair follicle differentiation and a myxoid, adipocytic, chondroid, and/or fibrous stroma. The pathologic diagnoses were all consistent with cutaneous benign mixed tumor (chondroid syringoma, pleomorphic adenoma). Follow-up ranged from 2 weeks to 12 months, although several patients failed, to keep scheduled follow-up appointments. No clinical recurrences were identified. Conclusions: Cutaneous benign mixed tumor may occur in the eyelid, and, although uncommon, should be included in the differential diagnosis of firm, nodular eyelid tumors. The histopathologic features are similar to those seen in this tumor type arising in. other areas of the body. Preoperative consideration of this diagnostic possibility may allow the surgeon to plan for complete excision, thereby reducing the possibility of recurrence or malignant transformation. C1 Sungkyonkwan Univ, Sch Med, Seoul, South Korea. Hop Cantonal Fribourg, Clin Ophthalm, Fribourg, Switzerland. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Community Hosp, Tampa, FL USA. Madigan Army Med Ctr, Dept Ophthalmol, Tacoma, WA 98431 USA. Stanford Univ, Dept Ophthalmol, Palo Alto, CA 94304 USA. Med Coll Wisconsin, Inst Eye, Milwaukee, WI 53226 USA. Mayo Clin, Dept Ophthalmol, Rochester, MN 55902 USA. Kosin Univ, Coll Med, Dept Ophthalmol, Pusan, South Korea. Eye Hlth Serv, Quincy, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Woog, JJ (reprint author), Mayo Clin, Dept Ophthalmol, Rochester, MN 55902 USA. EM woog.john@mayo.edu NR 30 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAR PY 2004 VL 20 IS 2 BP 110 EP 116 DI 10.1097/01.IOP.0000117337.65340.E5 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 804TP UT WOS:000220321300006 PM 15083078 ER PT J AU Nassif, N Cense, B Park, BH Yun, SH Chen, TC Bouma, BE Tearney, GJ de Boer, JF AF Nassif, N Cense, B Park, BH Yun, SH Chen, TC Bouma, BE Tearney, GJ de Boer, JF TI In vivo human retinal imaging by ultrahigh-speed spectral domain optical coherence tomography SO OPTICS LETTERS LA English DT Article ID TIME AB An ultrahigh-speed spectral domain optical coherence tomography (SD-OCT) system is presented that achieves acquisition rates of 29,300 depth profiles/s. The sensitivity of SD-OCT and time domain OCT (TD-OCT) are experimentally compared, demonstrating a 21.7-dB improvement of SD-OCT over TD-OCT. In. vivo images of the human retina are presented, demonstrating the ability to acquire high-quality structural images with an axial resolution of 6 mum at ultrahigh speed and with an ocular exposure level of less than 600 muW. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Nassif, N (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 724, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [1R24 EY12877] NR 12 TC 368 Z9 371 U1 4 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2004 VL 29 IS 5 BP 480 EP 482 DI 10.1364/OL.29.000480 PG 3 WC Optics SC Optics GA 775GC UT WOS:000189031500021 PM 15005199 ER PT J AU Sung, EC Friedlander, AH Kobashigawa, JA AF Sung, EC Friedlander, AH Kobashigawa, JA TI The prevalence of calcified carotid atheromas on the panoramic radiographs of patients with dilated cardiomyopathy SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID CARDIAC TRANSPLANTATION; HEART-FAILURE; STROKE; ATHEROSCLEROSIS; ONSET; RISK AB Objective. Individuals with dilated cardiomyopathy (DCM) often die from heart failure without a transplant. Of those who do receive a transplant, a significant number suffer a perioperative stroke, although the cause is often in doubt. Our study attempts to determine whether the prevalence of calcified carotid artery atheromas, a known cause of stroke, is greater on the panoramic radiographs of individuals with DCM than it is among controls. Study design. Twenty-seven persons [mean age 62.3 years] enrolled in the UCLA Cardiac Transplantation Program were provided a panoramic radiograph. An age-matched, atherogenic risk-matched cohort of 54 patients free of DCM served as controls. The radiographs of patients in each group were examined for the presence of calcified carotid atheromas. Results. Nine of the 27 patients with DCM had calcified atheromas, whereas only 2 of the 54 patients in the control group had such lesions. This difference was statistically significant (P < .001). Conclusions. Panoramic radiographs may be helpful in identifying some DCM patients with occult carotid artery atherosclerosis who may be at risk for a subsequent stroke. C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Hosp Dent Serv, Ctr Med, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Cardiac Transplant Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Friedlander, AH (reprint author), Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. EM arthur.friedlander@med.va.gov NR 30 TC 23 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAR PY 2004 VL 97 IS 3 BP 404 EP 407 DI 10.1016/j.tripleo.2003.08.025 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 803NO UT WOS:000220238000023 PM 15024368 ER PT J AU Lai, WFT Chang, CH Tang, Y Bronson, R Tung, CH AF Lai, WFT Chang, CH Tang, Y Bronson, R Tung, CH TI Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE osteoarthritis; cathepsin B; near-infrared fluorescence; collagenase; imaging ID FEMORAL-HEAD CARTILAGE; RHEUMATOID-ARTHRITIS; ARTICULAR-CARTILAGE; SYNOVIAL-MEMBRANE; ENZYME-ACTIVITY; MICE; INTERLEUKIN-1; CHONDROCYTES; EXPRESSION; INJECTION AB Objective: Osteoarthritis is currently diagnosed utilizing X-ray and MRI-techniques, both of which are based on the morphological changes of tissue. However, once changes are detected, the tissue has an irreversible defect. This study investigates early diagnosis of CA on a molecular basis using a recently developed cathepsin B sensitive near-infrared (NIR) fluorescent probe. Method: Twelve male nude mice were induced osteoarthritis by intra-articular injection of collagenase (1.0%, w/v) into the right knee joint. The left knee joint served as the negative control. The cathepsin B NIR probe is activated by arthritis-associated cathepsin B, thus resulting in the emission of an intensive NIR fluorescence signal which can be detected in vivo. NIR fluorescence signals were acquired on an optical imaging system using an excitation wavelength of 610-650 nm and an emission wavelength of 680-720 nm. Results: Mild to moderate degenerative cartilage was observed 1 month after collagenase injection. NIR fluorescence imaging of mice showed approximately a 3-fold difference in signal intensity between osteoarthritic and normal joints 24 In after intravenous injection of the reporter probe. Immunohistochemical evaluation also revealed cathepsin B expression in the arthritic lesion of fernorotibia joints, and not in the control contra-lateral knee joints. Conclusion: As the cathepsin B activatable NIR fluorescent imaging showed a significant difference between the osteoarthritic and normal joints, the cathepsin B activatable NIR fluorescent probe thus offers a potential new imaging technology for early OA diagnosis. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Tufts Univ, Sch Vet Med, Dept Biol Sci, North Grafton, MA 01536 USA. RP Tung, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th At,Rm 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu RI leu, borwen/K-8547-2012; OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R33-CA88365] NR 28 TC 45 Z9 46 U1 1 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD MAR PY 2004 VL 12 IS 3 BP 239 EP 244 DI 10.1016/j.joca.2003.11.005 PG 6 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 779EP UT WOS:000189282600007 PM 14972341 ER PT J AU Stewart, MG Smith, TL Weaver, EM Witsell, DL Yueh, B Hannley, MT Johnson, JT AF Stewart, MG Smith, TL Weaver, EM Witsell, DL Yueh, B Hannley, MT Johnson, JT CA Nose Study Invest TI Outcomes after nasal septoplasty: Results from the Nasal Obstruction Septoplasty Effectiveness (NOSE) study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; FUNCTIONAL SEPTOPLASTY; SEPTAL SURGERY; HEALTH-STATUS; RHINOMANOMETRY; RHINOSINUSITIS; HYPERTROPHY; TURBINATE; SYMPTOMS AB OBJECTIVE. Our goal was to assess disease-specific quality of life outcomes after nasal septoplasty in adults with nasal obstruction. DESIGN, SETTINGS, AND PATIENTS: We conducted a prospective observational outcomes multicenter study with 14 sites and 16 investigators, including private practice and academic settings. Patients had had septal deviation and symptomatic nasal obstruction for at least 3 months, and medical management had failed. METHODS: Patients with septal deviation completed a validated outcomes instrument (the Nasal Obstruction Septoplasty Effectiveness (NOSE) scale) before and 3 and 6 months after septoplasty, with or without partial turbinectomy. RESULTS: Fifty-nine patients underwent surgery; there was a significant improvement in mean NOSE score at 3 months after septoplasty (67.5 versus 23.1, P < 0.0001), and this improvement was unchanged at 6 months. Patient satisfaction was very high, and patients used significantly fewer nasal medications. CONCLUSIONS: In patients with septal deformity, nasal septoplasty results in significant improvement in disease-specific quality of life, high patient satisfaction, and decreased medication use. C1 Baylor Coll Med, Bobby R Alford Dept Otorinolaryngol & Communicat, Houston, TX 77030 USA. Med Coll Wisconsin, Dept Otolaryngol Head & Neck Surg, Milwaukee, WI 53226 USA. VA Puget Sound Healthcare Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. Duke Univ, Sch Med, Dept Surg, Div Otolaryngol Head & Neck Surg, Durham, NC 27706 USA. Amer Acad Otolaryngol, Head & Neck Surg Fdn, Alexandria, VA USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol Head & Neck Surg, Pittsburgh, PA 15261 USA. RP Stewart, MG (reprint author), Baylor Coll Med, Bobby R Alford Dept Otorinolaryngol & Communicat, 1 Baylor Plaza,NA-102, Houston, TX 77030 USA. EM mgstew@bcm.tmc.edu OI Yueh, Bevan/0000-0003-1380-1053 FU NHLBI NIH HHS [HL068849, K23 HL068849, K23 HL068849-01A2] NR 22 TC 152 Z9 158 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2004 VL 130 IS 3 BP 283 EP 290 DI 10.1016/j.otohns.2003.12.004 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808NE UT WOS:000220575000001 PM 15054368 ER PT J AU Wong, BJF Zhao, YH Yamaguchi, M Nassif, N Chen, ZP De Boer, JF AF Wong, BJF Zhao, YH Yamaguchi, M Nassif, N Chen, ZP De Boer, JF TI Imaging the internal structure of the rat cochlea using optical coherence tomography at 0.827 mu m and 1.3 mu m SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the Western Section of the Triological-Society CY JAN 06-07, 2001 CL CARLSBAD, CA SP Triol Soc, Western Sect ID HUMAN SKIN; SPEED AB OBJECTIVE: The purpose of this study was to use high-speed optical coherence tomography (OCT) to obtain cross-sectional images of the rat cochlea. STUDY DESIGN AND METHODS: The cochleae of Sprague-Dawley rats were imaged within 2 to 4 hours after death. Specimens were prepared by removing the bulla to expose the mesotympanum; some images were obtained in intact temporal bones removed from the cranium. The central element of an OCT imaging device is a Michelson interferometer combined with a low-coherence light source. This study used 2 OCT systems with different light sources: 1) a semiconductor optical amplifier operating and 2) a superluminescent diode with peak emissions wavelengths of 1.3 mum and 827 nm, respectively. Images (1.87 x 2.00 mm or 1.87 x 1.00 mm, 10 x 10 mum pixel resolution) were acquired at a frame rate of 1 Hz. Cross-sectional images at 100- mum increments were obtained from a medial -to- lateral direction. RESULTS: The scala vestibuli, scala media, scala tympani, modiolus, spiral ligament, and several turns of the cochlea were identified. CONCLUSION: These images reflect the ability of OCT to provide images of the internal cochlea structure with micron scale resolution and at near-real time frame rates. C1 Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. Univ Calif Irvine, Dept Otolaryngol Head & Neck Surg, Orange, CA 92668 USA. Univ Calif Irvine, Samueli Sch Engn, Dept Biomed Engn, Irvine, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Cambridge, MA 02138 USA. RP Wong, BJF (reprint author), Univ Calif Irvine, Beckman Laser Inst & Med Clin, 1002 Hlth Sci Rd E, Irvine, CA 92612 USA. EM bjfwong@bli.uci.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [1 R24EY 12877-01]; NIDCD NIH HHS [DC00170-01]; NIGMS NIH HHS [GM 58785] NR 8 TC 31 Z9 31 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2004 VL 130 IS 3 BP 334 EP 338 DI 10.1016/j.otohns.2003.11.007 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808NE UT WOS:000220575000008 PM 15054375 ER EF