FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hoshino, K Ly, HQ Pomerantseva, I Takewa, Y Yoneyama, R Kawase, Y DeGrande, AM Frangioni, JV Hajjar, RJ AF Hoshino, Kozo Ly, Hung Q. Pomerantseva, Irina Takewa, Yoshiaki Yoneyama, Ryuichi Kawase, Yoshiaki DeGrande, Alec M. Frangioni, John V. Hajjar, Roger J. TI In Vivo Fluorescence Tracking System for Cardiac Stem Cell Therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Hoshino, Kozo; Ly, Hung Q.; Pomerantseva, Irina; Takewa, Yoshiaki; Yoneyama, Ryuichi; Kawase, Yoshiaki; Hajjar, Roger J.] Massachusettes Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. [Hoshino, Kozo; Ly, Hung Q.; Pomerantseva, Irina; Takewa, Yoshiaki; Yoneyama, Ryuichi; Kawase, Yoshiaki; Hajjar, Roger J.] Massachusettes Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA USA. [DeGrande, Alec M.; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [DeGrande, Alec M.; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [DeGrande, Alec M.; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Mol Imaging Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 230 BP S88 EP S88 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501154 ER PT J AU Kuruppu, D Zhu, AJ Yu, MX Brownell, AL Tanabe, KK AF Kuruppu, Darshini Zhu, Aijun Yu, Meixiang Brownell, Anna-Liisa Tanabe, Kenneth K. TI Imaging HSV-1 Viral Oncolysis of Colon Cancer Cells by microPET SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Kuruppu, Darshini; Zhu, Aijun; Yu, Meixiang; Brownell, Anna-Liisa; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 306 BP S117 EP S117 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501230 ER PT J AU Lanuti, M Goodwin, JM Tanabe, KK AF Lanuti, Michael Goodwin, Jonathan M. Tanabe, Kenneth K. TI Combined Oncolysis and Anti-Angiogenesis Gene Therapy Using a Herpes Simplex Virus Expressing Endostatin in a Murine Lung Cancer Model SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Lanuti, Michael; Goodwin, Jonathan M.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 656 BP S252 EP S253 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502056 ER PT J AU Lebeche, D Sakata, S Sakata, Y Sakata, N Chemaly, ER Takaki, M Hajjar, RJ AF Lebeche, Djamel Sakata, Susumu Sakata, Yuri Sakata, Naoya Chemaly, Elie R. Takaki, Miyako Hajjar, Roger J. TI Gene Expression Profiles in Diabetic Cardiomyopathy Following SERCA2a Gene Transfer SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Lebeche, Djamel; Chemaly, Elie R.; Hajjar, Roger J.] Massachusetts Gen Hosp, Carrdiovasc Res Ctr, Charlestown, MA USA. [Sakata, Susumu; Sakata, Yuri; Sakata, Naoya; Takaki, Miyako] Nara Med Univ, Dept Physiol 2, Kashihara, Nara 634, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 237 BP S91 EP S91 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501161 ER PT J AU LeRoy, SG Comer, LA Costa, FF Broekman, MLD Sena-Esteves, M AF LeRoy, Stanley G. Comer, Laryssa A. Costa, Fabricio F. Broekman, Marike L. D. Sena-Esteves, Miguel TI Mosaic AAV Vectors Display Novel Properties for Neuronal Transduction SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [LeRoy, Stanley G.; Comer, Laryssa A.; Costa, Fabricio F.; Broekman, Marike L. D.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [LeRoy, Stanley G.; Comer, Laryssa A.; Costa, Fabricio F.; Broekman, Marike L. D.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Broekman, Marike L. D.] Univ Med Ctr Utrecht, Rudolph Magnus Inst Neurosci, Dept Pharmacol & Anat, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 491 BP S190 EP S190 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501415 ER PT J AU Liu, TC Zhang, TG Fukuhara, H Kuroda, T Todo, T Martuza, RL Rabkin, SD Kurtz, A AF Liu, Ta-Chiang Zhang, Tingguo Fukuhara, Hiroshi Kuroda, Toshi Todo, Tomoki Martuza, Robert L. Rabkin, Samuel D. Kurtz, Andreas TI Novel Oncolytic HSV Armed with Platelet Factor 4, an Antiangiogenic Agent, Shows Enhanced Efficacy SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Liu, Ta-Chiang; Zhang, Tingguo; Fukuhara, Hiroshi; Kuroda, Toshi; Todo, Tomoki; Martuza, Robert L.; Rabkin, Samuel D.; Kurtz, Andreas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurosurg Lab,Brain Tumor Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 159 BP S62 EP S62 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501083 ER PT J AU Martin, DR Cachon-Gonzalez, B Sena-Esteves, M Hwang, M Gentry, AS Morrison, NE Cox, NR Cox, TM Baker, HJ AF Martin, Douglas R. Cachon-Gonzalez, Begona Sena-Esteves, Miguel Hwang, Misako Gentry, Atoska S. Morrison, Nancy E. Cox, Nancy R. Cox, Timothy M. Baker, Henry J. TI Adeno-Associated Virus Gene Therapy of Feline Gangliosidosis SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Martin, Douglas R.; Hwang, Misako; Gentry, Atoska S.; Morrison, Nancy E.; Cox, Nancy R.; Baker, Henry J.] Auburn Univ, Scott Ritchey Res Ctr, Auburn, AL 36849 USA. [Cachon-Gonzalez, Begona; Cox, Timothy M.] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. [Sena-Esteves, Miguel] Harvard Univ, Ctr Neurosci, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 889 BP S342 EP S342 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502287 ER PT J AU Nagano, S Perentes, JY Jain, RK Boucher, Y AF Nagano, Satoshi Perentes, Jean Y. Jain, Rakesh K. Boucher, Yves TI Paclitaxel-TRAIL Enhances the Distribution of Oncolytic Herpes Simplex Virus-1 in a Human Mammary Carcinoma Xenograft SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Nagano, Satoshi; Perentes, Jean Y.; Jain, Rakesh K.; Boucher, Yves] Massachesetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 45 BP S19 EP S19 DI 10.1016/j.ymthe.2006.08.059 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933500046 ER PT J AU Pike, L Wang, S AF Pike, Lisa Wang, Sam TI Bioluminescence Imaging of a Tetanus Toxin C-Terminal Fusion Protein after Vector Delivery SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Pike, Lisa; Wang, Sam] Massachusetts Gen Hosp, Neurosci Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 162 BP S63 EP S63 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501086 ER PT J AU Prabhakar, S Messerli, S Rabkin, S Martuza, R Breakefield, XO AF Prabhakar, Shilpa Messerli, Shanta Rabkin, Samuel Martuza, Robert Breakefield, Xandra O. TI Treatment of Experimental Schwannomas with HSV Recombinant and Amplicon Vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Prabhakar, Shilpa; Messerli, Shanta; Rabkin, Samuel; Martuza, Robert; Breakefield, Xandra O.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 151 BP S59 EP S59 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501075 ER PT J AU Sanford, JD Oehmig, A Perry, KF Breakefield, XO Cortes, ML AF Sanford, Jocelyn D. Oehmig, Angelika Perry, Katherine F. Breakefield, Xandra O. Cortes, Maria L. TI Targeted Transgene Integration of the Human ATM cDNA Mediated by HSV/AAV Hybrid Amplicon Vector SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Sanford, Jocelyn D.; Oehmig, Angelika; Perry, Katherine F.; Breakefield, Xandra O.; Cortes, Maria L.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 252 BP S96 EP S96 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501176 ER PT J AU Tannous, BA Grimm, J Perry, KF Chen, JW Ralph, W Xandra, BO AF Tannous, Bakhos A. Grimm, Jan Perry, Katherine F. Chen, John W. Ralph, Weissleder Xandra, Breakefield O. TI Metabolic Biotinylation of Cell Surface Receptors for In Vivo Imaging SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Tannous, Bakhos A.; Grimm, Jan; Chen, John W.; Ralph, Weissleder; Xandra, Breakefield O.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Tannous, Bakhos A.; Perry, Katherine F.; Xandra, Breakefield O.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. [Tannous, Bakhos A.; Xandra, Breakefield O.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 1001 BP S386 EP S386 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502398 ER PT J AU Tannous, BA Perry, KF Sena-Esteves, M Garcias-Anoveros, J Jacobs, A Corey, DP Weissleder, R Breakefield, XO AF Tannous, Bakhos A. Perry, Katherine F. Sena-Esteves, Miguel Garcias-Anoveros, Jaime Jacobs, Andreas Corey, David P. Weissleder, Ralph Breakefield, Xandra O. TI Tumor Therapy Via Vector-Regulated Expression of Mutant Sodium Channel SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Tannous, Bakhos A.; Weissleder, Ralph; Breakefield, Xandra O.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Tannous, Bakhos A.; Perry, Katherine F.; Sena-Esteves, Miguel; Breakefield, Xandra O.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. [Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. [Garcias-Anoveros, Jaime] Northwestern Univ, Dept Anesthesiol, Feinberg Sch Med, Chicago, IL 60611 USA. [Jacobs, Andreas] Univ Cologne, D-50931 Cologne, Germany. [Corey, David P.] Harvard Univ, Sch Med, Howard Hughes Med Inst & Neurobiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 959 BP S370 EP S370 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933502357 ER PT J AU Yoneyama, R Palomeque, J Hoshino, K De Grand, AM Frangioni, JV Hajjar, RJ AF Yoneyama, Ryuichi Palomeque, Julieta Hoshino, Kozo De Grand, Alec M. Frangioni, John V. Hajjar, Roger Joseph TI In Vivo Tracking of Long Term Gene Expression of AAV1 Using Fluorescence Imaging System SO MOLECULAR THERAPY LA English DT Meeting Abstract C1 [Yoneyama, Ryuichi; Palomeque, Julieta; Hoshino, Kozo; Hajjar, Roger Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [De Grand, Alec M.; Frangioni, John V.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 EI 1525-0024 J9 MOL THER JI Mol. Ther. PD MAY PY 2006 VL 13 SU 1 MA 118 BP S48 EP S49 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA V32EC UT WOS:000208933501042 ER PT J AU Tarsy, D Baldessarini, RJ AF Tarsy, D Baldessarini, RJ TI Epidemiology of tardive dyskinesia: Is risk declining with modern antipsychotics? SO MOVEMENT DISORDERS LA English DT Review DE atypical antipsychotic drugs; extrapyramidal syndromes; movement disorders; atypical neuroleptics; tardive dyskinesia ID INDUCED MOVEMENT-DISORDERS; ATYPICAL ANTIPSYCHOTICS; OLDER PATIENTS; SCHIZOAFFECTIVE DISORDER; EXTRAPYRAMIDAL SYNDROMES; NEUROLEPTIC MEDICATIONS; RISPERIDONE TREATMENT; CLOZAPINE THERAPY; SCHIZOPHRENIA; PREVALENCE AB Second-generation antipsychotic drugs (APDs), including aripiprazole, clozapine, olanzapine, risperidone, quetiapine, and ziprasidone dominate outpatient and inpatient clinical practice, having largely displaced the older neuroleptics. Modern APDs have relatively low risk for acute extrapyramidal syndromes characteristic of older neuroleptics, particularly acute dystonia and Parkinsonism, with variable risks of akathisia and the rare neuroleptic malignant syndrome. Anticipated reduction in risk of tardive dyskinesia (TD) is less well documented. Nearly 50 years after initial reports on TD, it is appropriate to reexamine the epidemiology of this potentially severe late adverse effect of long-term APD treatment in light of current research and practice. We compared recent estimates of incidence and prevalence of TD identified with some modern APDs to the epidemiology of TD in the earlier neuroleptic era. Such comparisons are confounded by complex modern APD regimens, uncommon exposure limited to a single modern APD, effects of previous exposure to typical neuroleptics, and neurological assessments that are rarely prospective or systematic. Available evidence suggests that the risk of TD may be declining, but longitudinal studies of patients never treated with traditional neuroleptics and exposed to only a single modern APD are required to quantify TD risks with specific drugs. Lono-term use of APDs should continue to be based on research-supported indications, with regular specific examination for emerging TD. (C) 2006 Movement Disorder Society. C1 Beth Israel Deaconess Med Ctr, Parkinsons Dis & Movement Disorders Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Boston, MA 02114 USA. RP Tarsy, D (reprint author), Beth Israel Deaconess Med Ctr, Parkinsons Dis & Movement Disorders Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM dtarsy@bidmc.harvard.edu NR 117 TC 101 Z9 102 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2006 VL 21 IS 5 BP 589 EP 598 DI 10.1002/mds.20823 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 044ZP UT WOS:000237712700001 PM 16532448 ER PT J AU Liang, TW Truax, AC Trojanowski, JQ Lee, VMY Stern, MB Kotzbauer, PT AF Liang, TW Truax, AC Trojanowski, JQ Lee, VMY Stern, MB Kotzbauer, PT TI Partial deficit of pantothenate kinase 2 catalytic activity in a case of tremor-predominant neurodegeneration with brain iron accumulation SO MOVEMENT DISORDERS LA English DT Article DE Hallervorden-Spatz syndrome; neurodegeneration with brain iron accumulation; pantothenate kinase; pantothenate kinase-associated neurodegeneration; tremor ID HALLERVORDEN-SPATZ-SYNDROME; KINASE-ASSOCIATED NEURODEGENERATION AB We describe an atypical case of pantothenate kinase-associated neurodegeneration (PKAN) in which slowly progressive arm tremor was the predominant symptom beginning at the age of 25, with late-onset dystonia and dysarthria developing at the age of 50. Compound heterozygous mutations resulting in missense amino acid substitutions G521R and I529V were identified in the pantothenate kinase (PANK2) gene. We demonstrate that while the G521R mutation results in an unstable and inactive protein, the previously unreported I529V substitution has no apparent effect on the stability or catalytic activity of PanK2. The phenotype that results from this combination of mutations suggests that atypical presentations of PKAN may arise from partial deficits in PanK2 catalytic activity. (C) 2006 Movement Disorder Society. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA. RP Liang, TW (reprint author), Jefferson Hosp Neurosci, 900 Walnut St,Suite 200, Philadelphia, PA 19107 USA. EM tsao-wei.liang@jefferson.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2006 VL 21 IS 5 BP 718 EP 722 DI 10.1002/mds.20797 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 044ZP UT WOS:000237712700024 PM 16450344 ER PT J AU Bayliss, PE Bellavance, KL Whitehead, GG Abrams, JM Aegerter, S Robbins, HS Cowan, DB Keating, MT O'Reilly, T Wood, JM Roberts, TM Chan, J AF Bayliss, PE Bellavance, KL Whitehead, GG Abrams, JM Aegerter, S Robbins, HS Cowan, DB Keating, MT O'Reilly, T Wood, JM Roberts, TM Chan, J TI Chemical modulation of receptor signaling inhibits regenerative angiogenesis in adult zebrafish SO NATURE CHEMICAL BIOLOGY LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; DRUG DISCOVERY; KINASE INHIBITORS; FIN REGENERATION; TYROSINE KINASES; SONIC-HEDGEHOG; VEGF; MORPHOGENESIS; EXPRESSION; GRIDLOCK AB We examined the role of angiogenesis and the need for receptor signaling using chemical inhibition of the vascular endothelial growth factor receptor in the adult zebrafish tail fin. Using a small-molecule inhibitor, we were able to exert precise control over blood vessel regeneration. An angiogenic limit to tissue regeneration was determined, as avascular tissue containing skin, pigment, neuronal axons and bone precursors could regenerate up to about 1 mm. This indicates that tissues can regenerate without direct interaction with endothelial cells and at a distance from blood supply. We also investigated whether the effects of chemical inhibition could be enhanced in zebrafish vascular mutants. We found that adult zebrafish, heterozygous for a mutation in the critical receptor effector phospholipase C gamma 1, show a greater sensitivity to chemical inhibition. This study illustrates the utility of the adult zebrafish as a new model system for receptor signaling and chemical biology. C1 Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Novartis Pharma AG, CH-4002 Basel, Switzerland. RP Chan, J (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. EM joanne.chan@childrens.harvard.edu FU NHLBI NIH HHS [R01 HL068915, R01 HL068915-05A1] NR 48 TC 73 Z9 78 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD MAY PY 2006 VL 2 IS 5 BP 265 EP 273 DI 10.1038/nchembio778 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 034VE UT WOS:000236957900013 PM 16565716 ER PT J AU Bonner-Weir, S Sharma, A AF Bonner-Weir, S Sharma, A TI Are there pancreatic progenitor cells from which new islets form after birth? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID BETA-CELLS; MASS; DIFFERENTIATION; PROLIFERATION; GROWTH; RATS C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 10 TC 43 Z9 48 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD MAY PY 2006 VL 2 IS 5 BP 240 EP 241 DI 10.1038/ncpendmet0186 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 038MS UT WOS:000237226500002 PM 16932290 ER PT J AU Sonis, ST AF Sonis, ST TI Can oral glutamine prevent mucositis in children undergoing hematopoietic stem-cell transplantation? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE glutamine; hematopoietic stem-cell transplantation; mucositis; pediatric ID BONE-MARROW-TRANSPLANTATION C1 Brigham & Womens Hosp, Div Dent, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, Div Dent, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org NR 6 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAY PY 2006 VL 3 IS 5 BP 244 EP 245 DI 10.1038/ncponc0492 PG 2 WC Oncology SC Oncology GA 042TG UT WOS:000237551800007 PM 16683001 ER PT J AU Babitt, JL Huang, FW Wrighting, DM Xia, Y Sidis, Y Samad, TA Campagna, JA Chung, RT Schneyer, AL Woolf, CJ Andrews, NC Lin, HY AF Babitt, JL Huang, FW Wrighting, DM Xia, Y Sidis, Y Samad, TA Campagna, JA Chung, RT Schneyer, AL Woolf, CJ Andrews, NC Lin, HY TI Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression SO NATURE GENETICS LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; 1Q-LINKED JUVENILE HEMOCHROMATOSIS; ANTIMICROBIAL PEPTIDE HEPCIDIN; GROWTH-FACTOR-BETA; IRON OVERLOAD; GENE-EXPRESSION; LIVER-CELLS; I RECEPTOR; MOUSE; INFLAMMATION AB Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency induces iron overload, whereas hepcidin excess induces anemia. Mutations in the gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload and correlate with low hepcidin levels, suggesting that hemojuvelin positively regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance molecule (RGM) family, which also includes the bone morphogenetic protein (BMP) coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP coreceptor and that hemojuvelin mutants associated with hemochromatosis have impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin expression, a process enhanced by hemojuvelin and blunted in Hfe2(-/-) hepatocytes. Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis: hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin expression. C1 Harvard Univ, Sch Med, Program Membrane Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Nephrol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Plast Res Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Lin, HY (reprint author), Harvard Univ, Sch Med, Program Membrane Biol, Boston, MA 02115 USA. EM hlin@partners.org OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [T32 HL07623]; NIDDK NIH HHS [F32 DK068997, DK-69533, DK-71837, F32 DK-068997, F32 DK068997-02, K08 DK075846, K08 DK075846-01, R01 DK066373, R01 DK066373-03] NR 50 TC 580 Z9 617 U1 1 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2006 VL 38 IS 5 BP 531 EP 539 DI 10.1038/ng1777 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 037LE UT WOS:000237147500014 PM 16604073 ER PT J AU Graham, RR Kozyrev, SV Baechler, EC Reddy, MPL Plenge, RM Bauer, JW Ortmann, WA Koeuth, T Escribano, MF Pons-Estel, B Petri, M Daly, M Gregersen, PK Martin, J Altshuler, D Behrens, TW Alarcon-Riquelme, ME AF Graham, RR Kozyrev, SV Baechler, EC Reddy, MPL Plenge, RM Bauer, JW Ortmann, WA Koeuth, T Escribano, MF Pons-Estel, B Petri, M Daly, M Gregersen, PK Martin, J Altshuler, D Behrens, TW Alarcon-Riquelme, ME CA Argentine Collaborative Grp Spanish Collaborative Grp TI A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus SO NATURE GENETICS LA English DT Article ID HUMAN GENE-EXPRESSION; INDUCTION; ALPHA; GENOME; DISEQUILIBRIUM; ACTIVATION; LINKAGE; BLOOD; CELLS AB Systemic lupus erythematosus (SLE) is a complex autoimmune disease(1) characterized by activation of the type I interferon (IFN) pathway(2-4). Here we convincingly replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele with SLE5 in four independent case-control cohorts (P = 4.4 x 10(-16)) and by family-based transmission disequilibrium test analysis (P = 0.0006). The rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5, allowing expression of several unique IRF5 isoforms. We also identify an independent cis-acting variant associated with elevated expression of IRF5 and linked to the exon 1B splice site. Haplotypes carrying the variant associated with elevated expression and lacking the exon 1B donor site do not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity. C1 Uppsala Univ, Rudbcek Lab, Unit Med Genet, Dept Genet & Pathol, S-75185 Uppsala, Sweden. MIT, Cambridge, MA 02142 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet Res & Mol Biol, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA. Hosp Virgen del Rocio, Serv Inmunol, Seville 41013, Spain. Sanatorio Parque, RA-2000 Rosario, Santa Fe, Argentina. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. CSIC, Inst Biomed Lopez Neyra, Granada 18100, Spain. RP Alarcon-Riquelme, ME (reprint author), Uppsala Univ, Rudbcek Lab, Unit Med Genet, Dept Genet & Pathol, S-75185 Uppsala, Sweden. EM behre001@umn.edu; marta.alarcon@genpat.uu.se RI Altshuler, David/A-4476-2009; Martin, Javier/B-8141-2008; LINGA REDDY, M.V. PRASAD/H-6330-2012; Gillespie, Emily/N-1265-2013; OI Altshuler, David/0000-0002-7250-4107; Gillespie, Emily/0000-0001-5261-3931; Alarcon Riquelme, Marta Eugenia/0000-0002-7632-4154 FU NCRR NIH HHS [M01-RR-00052]; NIAMS NIH HHS [AR 43727] NR 24 TC 415 Z9 425 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2006 VL 38 IS 5 BP 550 EP 555 DI 10.1038/ng1782 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 037LE UT WOS:000237147500016 PM 16642019 ER PT J AU Spinazzola, A Viscomi, C Fernandez-Vizarra, E Carrara, F D'Adamo, P Calvo, S Marsano, RM Donnini, C Weiher, H Strisciuglio, P Parini, R Sarzi, E Chan, A DiMauro, S Rotig, A Gasparini, P Ferrero, I Mootha, VK Tiranti, V Zeviani, M AF Spinazzola, A Viscomi, C Fernandez-Vizarra, E Carrara, F D'Adamo, P Calvo, S Marsano, RM Donnini, C Weiher, H Strisciuglio, P Parini, R Sarzi, E Chan, A DiMauro, S Rotig, A Gasparini, P Ferrero, I Mootha, VK Tiranti, V Zeviani, M TI MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion SO NATURE GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; KIDNEY-DISEASE; GENE MPV17; MUTATIONS; IMPORT; DEFICIENCY; KINASE; CHAIN AB The mitochondrial (mt) DNA depletion syndromes (MDDS) are genetic disorders characterized by a severe, tissue-specific decrease of mtDNA copy number, leading to organ failure. There are two main clinical presentations: myopathic (OMIM 609560) and hepatocerebral(1) (OMIM 251880). Known mutant genes, including TK2 (ref. 2), SUCLA2 (ref. 3), DGUOK (ref. 4) and POLG(5,6), account for only a fraction of MDDS cases(7). We found a new locus for hepatocerebral MDDS on chromosome 2p21-23 and prioritized the genes on this locus using a new integrative genomics strategy. One of the top-scoring candidates was the human ortholog of the mouse kidney disease gene Mpv17 (ref. 8). We found disease-segregating mutations in three families with hepatocerebral MDDS and demonstrated that, contrary to the alleged peroxisomal localization of the MPV17 gene product(9), MPV17 is a mitochondrial inner membrane protein, and its absence or malfunction causes oxidative phosphorylation (OXPHOS) failure and mtDNA depletion, not only in affected individuals but also in Mpv17(-/-) mice. C1 Natl Neurol Inst C Besta, Unit Mol Neurogenet, Pierfranco & Luisa Mariani Ctr Study Childrens Mi, I-20126 Milan, Italy. Telethon Inst Genet Med TIGEM, Linkage Unit & Serv, I-80131 Naples, Italy. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02446 USA. Harvard Univ, Cambridge, MA 02446 USA. Univ Parma, Dept Genet Anthropol Evolut, I-43100 Parma, Italy. Univ Appl Sci Bonn Rhein Sieg, D-53359 Bonn, Germany. Univ Catanzaro Magna Graecia, Dept Clin & Expt Med, I-88100 Catanzaro, Italy. Milano Bicocca State Univ, Univ Hosp, Pediat Unit, Pierfranco & Luisa Mariani Ctr Study Childrens Me, I-20052 Monza, Italy. Hop Necker Enfants Malad, Dept Genet, F-75015 Paris, France. Hop Necker Enfants Malad, INSERM Unit U393, F-75015 Paris, France. Univ Alberta, Dept Med Genet, Edmonton, AB T6G 2H7, Canada. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Univ Trieste, Dept Med Genet, I-34137 Trieste, Italy. RP Zeviani, M (reprint author), Natl Neurol Inst C Besta, Unit Mol Neurogenet, Pierfranco & Luisa Mariani Ctr Study Childrens Mi, I-20126 Milan, Italy. EM zeviani@istituto-besta.it RI Donnini, Claudia/B-5548-2015; Tiranti, Valeria/J-8233-2016; Viscomi, Carlo/R-1940-2016; Marsano, Rene'/B-9640-2012; d'Adamo, Adamo Pio/G-4064-2011; Zeviani, Massimo/K-2891-2014 OI Donnini, Claudia/0000-0002-4901-2358; Tiranti, Valeria/0000-0002-3584-7338; Marsano, Rene'/0000-0001-8450-1010; d'Adamo, Adamo Pio/0000-0001-9367-4909; FU Telethon [GGP030039, TGM03P12, TGM06S01] NR 30 TC 233 Z9 238 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2006 VL 38 IS 5 BP 570 EP 575 DI 10.1038/ng1765 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 037LE UT WOS:000237147500020 PM 16582910 ER PT J AU Calvo, S Jain, M Xie, XH Sheth, SA Chang, B Goldberger, OA Spinazzola, A Zeviani, M Carr, SA Mootha, VK AF Calvo, S Jain, M Xie, XH Sheth, SA Chang, B Goldberger, OA Spinazzola, A Zeviani, M Carr, SA Mootha, VK TI Systematic identification of human mitochondrial disease genes through integrative genomics SO NATURE GENETICS LA English DT Article ID RESPIRATORY-CHAIN DISORDERS; HETEROGENEITY; PROTEINS; SEQUENCE; LOCUS; PROTEOME; DATABASE; MUSCLE; MOUSE AB The majority of inherited mitochondrial disorders are due to mutations not in the mitochondrial genome ( mtDNA) but rather in the nuclear genes encoding proteins targeted to this organelle. Elucidation of the molecular basis for these disorders is limited because only half(1,2) of the estimated 1,500 mitochondrial proteins(3) have been identified. To systematically expand this catalog, we experimentally and computationally generated eight genome-scale data sets, each designed to provide clues as to mitochondrial localization: targeting sequence prediction, protein domain enrichment, presence of cis-regulatory motifs, yeast homology, ancestry, tandem-mass spectrometry, coexpression and transcriptional induction during mitochondrial biogenesis. Through an integrated analysis we expand the collection to 1,080 genes, which includes 368 novel predictions with a 10% estimated false prediction rate. By combining this expanded inventory with genetic intervals linked to disease, we have identified candidate genes for eight mitochondrial disorders, leading to the discovery of mutations in MPV17 that result in hepatic mtDNA depletion syndrome(4). The integrative approach promises to better define the role of mitochondria in both rare and common human diseases. C1 MIT, Broad Inst, Cambridge, MA 02142 USA. Harvard Univ, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. Natl Neurol Inst C Besta, Unite Mol Neurogenet, I-20126 Milan, Italy. RP Mootha, VK (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02142 USA. EM vamsi@hms.harvard.edu RI Zeviani, Massimo/K-2891-2014 NR 30 TC 211 Z9 220 U1 3 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2006 VL 38 IS 5 BP 576 EP 582 DI 10.1038/ng1776 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 037LE UT WOS:000237147500021 PM 16582907 ER PT J AU Ueki, K Okada, T Hu, J Liew, CW Assmann, A Dahlgren, GM Peters, JL Shackman, JG Zhang, M Artner, I Satin, LS Stein, R Holzenberger, M Kennedy, RT Kahn, CR Kulkarni, RN AF Ueki, K Okada, T Hu, J Liew, CW Assmann, A Dahlgren, GM Peters, JL Shackman, JG Zhang, M Artner, I Satin, LS Stein, R Holzenberger, M Kennedy, RT Kahn, CR Kulkarni, RN TI Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes SO NATURE GENETICS LA English DT Article ID RECEPTOR SUBSTRATE-1; PROTEIN-KINASE; MICE; SECRETION; ROLES; MAFA; MASS; HYPERINSULINEMIA; KNOCKOUT; CHANNELS AB An appropriate beta cell mass is pivotal for the maintenance of glucose homeostasis(1). Both insulin and IGF-1 are important in regulation of beta cell growth and function ( reviewed in ref. 2). To define the roles of these hormones directly, we created a mouse model lacking functional receptors for both insulin and IGF-1 only in beta cells (beta DKO), as the hormones have overlapping mechanisms of action and activate common downstream proteins. Notably, bDKO mice were born with a normal complement of islet cells, but 3 weeks after birth, they developed diabetes, in contrast to mild phenotypes observed in single mutants(3,4). Normoglycemic 2-week-old beta DKO mice manifest reduced beta cell mass, reduced expression of phosphorylated Akt and the transcription factor MafA, increased apoptosis in islets and severely compromised b cell function. Analyses of compound knockouts showed a dominant role for insulin signaling in regulating beta cell mass. Together, these data provide compelling genetic evidence that insulin and IGF-I-dependent pathways are not critical for development of beta cells but that a loss of action of these hormones in b cells leads to diabetes. We propose that therapeutic improvement of insulin and IGF-I signaling in beta cells might protect against type 2 diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Hop St Antoine, INSERM U515, F-75571 Paris 12, France. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. EM Rohit.Kulkarni@joslin.harvard.edu RI Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU NIDDK NIH HHS [R01 DK066207, P01 DK042502, R01 DK046960, R01 DK067536] NR 30 TC 159 Z9 165 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2006 VL 38 IS 5 BP 583 EP 588 DI 10.1038/ng1787 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 037LE UT WOS:000237147500022 PM 16642022 ER PT J AU Cooper, AB Sawai, CM Sicinska, E Powers, SE Sicinski, P Clark, MR Aifantis, I AF Cooper, AB Sawai, CM Sicinska, E Powers, SE Sicinski, P Clark, MR Aifantis, I TI A unique function for cyclin D3 in early B cell development SO NATURE IMMUNOLOGY LA English DT Article ID COMMON LYMPHOID PROGENITORS; ADAPTER PROTEIN SLP-65; RECEPTOR-GAMMA CHAIN; TRANSCRIPTIONAL ACTIVATION; MOUSE DEVELOPMENT; HEAVY-CHAIN; BONE-MARROW; D2; INTERLEUKIN-7; D1 AB During hematopoiesis, stem cell proliferation is dependent on expression of the D-type cyclins. However, little is known about how each cyclin D contributes to the development of specific hematopoietic lineages. Here, analysis of Ccnd1(-/-), Ccnd2(-/-), Ccnd3(-/-) and Ccnd2(-/-) Ccnd3(-/-) mice showed that cyclin D3 was uniquely required for the development of pre-B cells. Transcription of Ccnd3 was dependent on expression of the common gamma-chain. In contrast, expression of the pre-B cell receptor and activation of 'downstream' signaling pathways prevented proteasome-mediated degradation of cyclin D3. Cyclin D3 has a key function in B cell development by integrating cytokine and pre-B cell receptor-dependent signals to expand the pool of pre-B cells that have successfully rearranged immunoglobulin heavy chain. C1 Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. RP Clark, MR (reprint author), Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. EM mclark@medicine.bsd.uchicago.edu; iaifanti@medicine.bsd.uchicago.edu FU NCI NIH HHS [R01CA105129]; NIGMS NIH HHS [R01GM52736] NR 49 TC 66 Z9 67 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2006 VL 7 IS 5 BP 489 EP 497 DI 10.1038/ni1324 PG 9 WC Immunology SC Immunology GA 035NT UT WOS:000237008800014 PM 16582912 ER PT J AU Shinohara, ML Lu, LR Bu, J Werneck, MBF Kobayashi, KS Glimcher, LH Cantor, H AF Shinohara, ML Lu, LR Bu, J Werneck, MBF Kobayashi, KS Glimcher, LH Cantor, H TI Osteopontin expression is essential for interferon-alpha production by plasmacytoid dendritic cells SO NATURE IMMUNOLOGY LA English DT Article ID ADAPTIVE IMMUNE-RESPONSES; MICE LACKING OSTEOPONTIN; TOLL-LIKE RECEPTOR-9; CD8 T-CELLS; I INTERFERON; CRESCENTIC GLOMERULONEPHRITIS; INTRACELLULAR OSTEOPONTIN; MULTIPLE-SCLEROSIS; CROSS-PRESENTATION; LUPUS AB The observation that the T-bet transcription factor allows tissue-specific upregulation of intracellular osteopontin (Opn-i) in plasmacytoid dendritic cells (pDCs) suggests that Opn might contribute to the expression of interferon-alpha (IFN-alpha) in those cells. Here we show that Opn deficiency substantially reduced Toll-like receptor 9 (TLR9)-dependent IFN-alpha responses but spared expression of transcription factor NF-kappa B-dependent proinflammatory cytokines. Shortly after TLR9 engagement, colocalization of Opn-i and the adaptor molecule MyD88 was associated with induction of transcription factor IRF7-dependent IFN-alpha gene expression, whereas deficient expression of Opn-i was associated with defective nuclear translocation of IRF7 in pDCs. The importance of the Opn-IFN-alpha pathway was emphasized by its essential involvement in cross-presentation in vitro and in anti herpes simplex virus 1 IFN-alpha response in vivo. The finding that Opn-i selectively coupled TLR9 signaling to expression of IFN-alpha but not to that of other proinflammatory cytokines provides new molecular insight into the biology of pDCs. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu RI Werneck, Miriam/H-5802-2012; Lu, Linrong/A-1429-2013; OI Lu, Linrong/0000-0002-0171-4115 FU NCI NIH HHS [CA48126, T32 CA070083, T32 CA70083]; NIAID NIH HHS [AI12184, AI48125, AI56296, P01 AI056296, R01 AI048125, R01 AI048126, R37 AI012184] NR 60 TC 205 Z9 223 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2006 VL 7 IS 5 BP 498 EP 506 DI 10.1038/ni1327 PG 9 WC Immunology SC Immunology GA 035NT UT WOS:000237008800015 PM 16604075 ER PT J AU O'Leary, JG Goodarzi, M Drayton, DL von Andrian, UH AF O'Leary, JG Goodarzi, M Drayton, DL von Andrian, UH TI T cell- and B cell-independent adaptive immunity mediated by natural killer cells SO NATURE IMMUNOLOGY LA English DT Article ID DELAYED-TYPE HYPERSENSITIVITY; RECEPTOR-GAMMA CHAIN; DENDRITIC CELLS; NK CELLS; IN-VIVO; CONTACT HYPERSENSITIVITY; NKG2D IMMUNORECEPTOR; MICE DEFICIENT; LYMPHOCYTE-T; ALPHA-BETA AB It is commonly believed that only T lymphocytes and B lymphocytes expressing recombination-dependent antigen-specific receptors mediate contact hypersensitivity responses to haptens. Here we found that mice devoid of T cells and B cells demonstrated substantial contact hypersensitivity responses to 2,4-dinitrofluorobenzene and oxazolone. Those responses were adaptive in nature, as they persisted for at least 4 weeks and were elicited only by haptens to which mice were previously sensitized. No contact hypersensitivity was induced in mice lacking all lymphocytes, including natural killer cells. Contact hypersensitivity responses were acquired by such mice after adoptive transfer of natural killer cells from sensitized donors. Transferable hapten-specific memory resided in a Ly49C-I+ natural killer subpopulation localized specifically in donor livers. These observations indicate that natural killer cells can mediate long-lived, antigen-specific adaptive recall responses independent of B cells and T cells. 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 Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL56949, P01 HL056949, T32 HL066987]; NIAID NIH HHS [AI061663]; NIAMS NIH HHS [AR42689, T32 AR07098-31]; NIDDK NIH HHS [T32 DK007191] NR 56 TC 371 Z9 387 U1 1 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2006 VL 7 IS 5 BP 507 EP 516 DI 10.1038/ni1332 PG 10 WC Immunology SC Immunology GA 035NT UT WOS:000237008800016 PM 16617337 ER PT J AU Sandoval, GM Duerr, JS Hodgkin, J Rand, JB Ruvkun, G AF Sandoval, GM Duerr, JS Hodgkin, J Rand, JB Ruvkun, G TI A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans SO NATURE NEUROSCIENCE LA English DT Article ID SYNTAXIN; MUTANTS AB Acetylcholine, a major excitatory neurotransmitter in Caenorhabditis elegans, is transported into synaptic vesicles by the vesicular acetylcholine transporter encoded by unc-17. The abnormal behavior of unc-17(e245) mutants, which have a glycine-to-arginine substitution in a transmembrane domain, is markedly improved by a mutant synaptobrevin with an isoleucine-to-aspartate substitution in its transmembrane domain. These results suggest an association of vesicular soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) components with vesicular neurotransmitter transporters. C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Ohio Univ, Dept Biol Sci, Athens, OH 45701 USA. Univ Oxford, Dept Biochem, Genet Unit, Oxford OX1 3QU, England. Oklahoma Med Res Fdn, Program Mol Cell & Dev Biol, Oklahoma City, OK 73104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biol Mol, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. EM ruvkun@molbio.mgh.harvard.edu FU Medical Research Council [G0000114]; NIGMS NIH HHS [R01 GM038679, R01 GM059642-11, R01 GM059642, R01 GM038679-18] NR 8 TC 16 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2006 VL 9 IS 5 BP 599 EP 601 DI 10.1038/nn1685 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 040YI UT WOS:000237417200007 PM 16604067 ER PT J AU Grabher, C von Boehmer, H Look, AT AF Grabher, C von Boehmer, H Look, AT TI Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia SO NATURE REVIEWS CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ONCOGENIC TRANSCRIPTION FACTORS; GENE-EXPRESSION SIGNATURES; ACUTE LYMPHOCYTIC-LEUKEMIA; HEMATOPOIETIC STEM-CELLS; LOOP-HELIX PROTEIN; N-RAS GENE; TRANSGENIC MICE; CHROMOSOMAL TRANSLOCATION; IN-VIVO AB The chromosomal translocation t(7; 9) in human T-cell acute lymphoblastic leukaemia (T-ALL) results in deregulated expression of a truncated, activated form of Notch 1 (TAN1) under the control of the T-cell receptor-beta (TCRB) locus. Although TAN1 efficiently induces T-ALL in mouse models, t( 7; 9) is present in less than 1% of human T-ALL cases. The recent discovery of novel activating mutations in NOTCH1 in more than 50% of human T-ALL samples has made it clear that Notch 1 is far more important in human T-ALL pathogenesis than previously suspected. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Grabher, C (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu RI Grabher, Clemens/H-2064-2013 NR 174 TC 249 Z9 256 U1 2 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2006 VL 6 IS 5 BP 347 EP 359 DI 10.1038/nrc1880 PG 13 WC Oncology SC Oncology GA 036FS UT WOS:000237057300012 PM 16612405 ER PT J AU Borsook, D Becerra, L Hargreaves, R AF Borsook, D Becerra, L Hargreaves, R TI A role for fMRI in optimizing CNS drug development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID TERM REPRODUCIBILITY ANALYSIS; IRRITABLE-BOWEL-SYNDROME; NERVE GROWTH-FACTOR; FUNCTIONAL MRI; HUMAN BRAIN; PHARMACOLOGICAL MRI; RECEPTOR AGONIST; NEUROPATHIC PAIN; WORKING-MEMORY; CENTRAL SENSITIZATION AB Drug development today needs to balance agility, speed and risk in defining the probability of success for molecules, mechanisms and therapeutic concepts. New techniques in functional magnetic resonance imaging (fMRI) promise to be part of a sequence that could transform drug development for disorders of the central nervous system (CNS) by examining brain systems and their functional activation dynamically. The brain is complex and multiple transmitters and intersecting brain circuits are implicated in many CNS disorders. CNS therapeutics are designed against specific CNS targets, many of which are unprecedented. The challenge is to reveal the functional consequences of these interactions to assess therapeutic potential. fMRI can help optimize CNS drug discovery by providing a key metric that can increase confidence in early decision-making, thereby improving success rates and reducing risk, development times and costs of drug development. C1 Harvard Univ, Sch Med, Imaging Ctr Drug Dev,McLean Hosp, Dept Psychiat,Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Merck & Co Inc, Imaging, West Point, PA 19486 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Imaging Ctr Drug Dev,McLean Hosp, Dept Psychiat,Massachusetts Gen Hosp, Cambridge, MA 02138 USA. EM dborsook@mclean.harvard.edu; lbecerra@mclean.harvard.edu; richard_hargreaves@merck.com NR 148 TC 115 Z9 120 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD MAY PY 2006 VL 5 IS 5 BP 411 EP 424 DI 10.1038/nrd2027 PG 14 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 039BB UT WOS:000237273400016 PM 16604100 ER PT J AU Huang, TT D'Andrea, AD AF Huang, TT D'Andrea, AD TI Regulation of DNA repair by ubiquitylation SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-C; RNA-POLYMERASE-II; FANCONI ANEMIA/BRCA PATHWAY; UBIQUITIN-BINDING DOMAINS; XERODERMA-PIGMENTOSUM; DEUBIQUITINATING ENZYMES; PROTEASOME INHIBITORS; MONOUBIQUITINATED PCNA; POLYUBIQUITIN CHAINS AB The process of ubiquitylation is best known for its role in targeting proteins for degradation by the proteasome. However, recent studies of DNA-repair and DNA-damage-response pathways have significantly broadened the scope of the role of ubiquitylation to include non-proteolytic functions of ubiquitin. These pathways involve the monoubiquitylation of key DNA-repair proteins that have regulatory functions in homologous recombination and translesion DNA synthesis, and involve the polyubiquitylation of nucleotide-excision-repair proteins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM alan_dandrea@dfci.harvard.edu NR 104 TC 177 Z9 180 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD MAY PY 2006 VL 7 IS 5 BP 323 EP 334 DI 10.1038/nrm1908 PG 12 WC Cell Biology SC Cell Biology GA 036FU UT WOS:000237057500012 PM 16633336 ER PT J AU Chen-Plotkin, AS Sadri-Vakill, G Yohrling, GJ Bravernan, MW Berin, CL Glajch, KE DiRocco, DP Farrella, LA Krainc, D Gines, S MacDonald, ME Cha, JHJ AF Chen-Plotkin, AS Sadri-Vakill, G Yohrling, GJ Bravernan, MW Berin, CL Glajch, KE DiRocco, DP Farrella, LA Krainc, D Gines, S MacDonald, ME Cha, JHJ TI Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE chromatin immunoprecipitation; transcription; gene regulation; transcription factor; Huntington's disease; polyglutamine ID RNA LEVELS DECREASE; MESSENGER-RNA; MOUSE MODELS; STRIATAL NEURONS; TRANSGENIC MICE; IN-VIVO; EXPRESSION; PROTEIN; CELLS; IMMUNOPRECIPITATION AB Huntington's disease (HD) is a neurodegenerative disease caused by expansion of a polyglutamine tract within the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis; recent evidence suggests a defect in Sp1-mediated transcription. We used chromatin immunoprecipitation (ChIP) assays followed by real-time PCR to quantify the association of Sp1 with individual genes. We find that, despite normal protein levels and normal to increased overall nuclear binding activity, Still has decreased binding to specific promoters of susceptible genes in transgenic HD Mouse brain, in striatal HD cells, and in human HD brain. Genes whose mRNA levels are decreased in HD have abnormal Sp1-DNA binding, whereas genes with unchanged mRNA levels have normal levels of Slat association. Moreover, the altered binding seen with Sp1 is not found with another transcription factor, NF-Y. These findings suggest that mutant huntingtin dissociates Sp1 from target promoters, inhibiting transcription of specific genes. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Massgen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA 02129 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Massgen Inst Neurodegenerat Dis, B114-2000 114 16th St, Charlestown, MA 02129 USA. EM cha@helix.mgh.harvard.edu OI Gines Padros, Silvia/0000-0002-9479-8185 FU NINDS NIH HHS [NS32765, NS045242, NS16367, NS38106] NR 33 TC 69 Z9 69 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2006 VL 22 IS 2 BP 233 EP 241 DI 10.1016/j.nbd.2005.11.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 040KS UT WOS:000237378000003 PM 16442295 ER PT J AU Kim, YJ Sapp, E Cuiffo, BG Sobin, L Yoder, J Kegel, KB Qin, ZH Detloff, P Aronin, N DiFiglia, M AF Kim, YJ Sapp, E Cuiffo, BG Sobin, L Yoder, J Kegel, KB Qin, ZH Detloff, P Aronin, N DiFiglia, M TI Lysosomal proteases are involved in generation of N-terminal huntingtin fragments SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntingtin proteolysis; cathepsin D; cathepsins B and L; aspartyl proteases; cysteine proteases; cleavage products A and B ID NEURONAL INTRANUCLEAR INCLUSIONS; AMYLOID PRECURSOR PROTEIN; CATHEPSIN-D; MUTANT HUNTINGTIN; RAT-BRAIN; WILD-TYPE; DISEASE; APOPTOSIS; ACTIVATION; EXPRESSION AB N-terminal mutant huntingtin (N-mhtt) fragments form inclusions and cause cell death in vitro. Mutant htt expression stimulates autophagy and increases levels of lysosomal proteases. Here, we show that lysosomal proteases, cathepsins D, B and L, affected mhtt processing and levels of cleavage products (cp) known as A and B, which form inclusions. Adding inhibitors of cathepsin D, B and L to clonal striatal cells reduced mhtt, especially mhtt fragment cp A. Mutant htt fully degraded in cathepsin-L-treated lysates but formed stable N-mhtt fragments upon exposure to cathepsin D. Mutagenesis analysis of htt cDNA suggested that cathepsin D and the protease for cp A may cleave htt in the same region. Brain lysates from HD knock-in mice expressed N-mhtt fragments that accumulated with cathepsin D treatment and declined with aspartyl protease inhibition. Findings implicate lysosomal proteases in formation of N-mhtt fragments and clearance of mhtt. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. Univ Massachusetts, Ctr Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Ctr Med, Dept Cell Biol, Worcester, MA 01655 USA. RP DiFiglia, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 114 16th St, Charlestown, MA 02129 USA. EM DiFiglia@helix.mgh.harvard.edu RI Kim, Yun Joong/E-7117-2015 OI Kim, Yun Joong/0000-0002-2956-1552 FU NINDS NIH HHS [NS 16367, NS 38194, NS35711] NR 38 TC 39 Z9 40 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2006 VL 22 IS 2 BP 346 EP 356 DI 10.1016/j.nbd.2005.11.012 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 040KS UT WOS:000237378000014 PM 16423528 ER PT J AU Malkani, R D'Souza, I Gwinn-Hardy, K Scheenberg, GD Hardya, J Momeni, P AF Malkani, R D'Souza, I Gwinn-Hardy, K Scheenberg, GD Hardya, J Momeni, P TI A MAPT mutation in a regulatory element upstream of exon 10 causes frontotemporal dementia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE MAPT; frontotemporal dementia; splicing ID TAU; CHROMOSOME-17; ASSOCIATION; EXPRESSION; GENE AB We report here the genetic analysis of a newly ascertained kindred in which frontotemporal dementia occurs in an apparent autosomal dominant fashion, and in which a novel MAPT gene mutation cosegregates with disease. Sequencing the MAPT gene in affected individuals revealed a change in intron 9. This finding supports earlier studies on the effect of a splice-accepting element in inclusion of exon 10 in the MAPT transcript. This mutation sheds light on a novel mechanism by which over-expression of 4-repeat tau leads to disease. Based on our current findings, we propose a novel mechanism by which intronic mutations can lead to frontotemporal dementia. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Inst Aging, Lab Neurogenet, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Cluster, Bethesda, MD 20892 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Momeni, P (reprint author), Natl Inst Aging, Lab Neurogenet, Porter Neurosci Bldg,35,Convent Dr, Bethesda, MD 20892 USA. EM momeni@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Hardy, John/C-2451-2009 FU Intramural NIH HHS; Medical Research Council [G0701075]; NIA NIH HHS [R01 AG1176] NR 9 TC 19 Z9 20 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAY PY 2006 VL 22 IS 2 BP 401 EP 403 DI 10.1016/j.nbd.2005.12.001 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 040KS UT WOS:000237378000019 PM 16503405 ER PT J AU Nimsky, C Ganslandt, O Merhof, D Sorensen, AG Fahlbusch, R AF Nimsky, Christopher Ganslandt, Oliver Merhof, Dorit Sorensen, A. Gregory Fahlbusch, Rudolf TI Intraoperative visualization of the pyramidal tract by diffusion-tensor-imaging-based fiber tracking SO NEUROIMAGE LA English DT Article DE diffusion tensor imaging; fiber tracking; functional neuronavigation; intraoperative imaging; major white matter tracts ID FUNCTIONAL MAGNETIC-RESONANCE; SPACE-OCCUPYING LESIONS; WHITE-MATTER TRACTS; BRAIN-TUMORS; MOTOR CORTEX; INITIAL-EXPERIENCE; GLIOMA SURGERY; GRADE GLIOMAS; IN-VIVO; NEURONAVIGATION AB Functional neuronavigation allows intraoperative visualization of cortical eloquent brain areas. Major white matter tracts, such as the pyramidal tract, can be delineated by diffusion-tensor-imaging based fiber tracking. These tractography data were integrated into 3-D datasets applied for neuronavigation by rigid registration of the diffusion images with standard anatomical image data so that their course could be superimposed onto the surgical field during resection of gliomas. Intraoperative high-field magnetic resonance imaging was used to compensate for the effects of brain shift, which amounted up to 8 mm. Despite image distortion of echo planar images, which was identified by non-linear registration techniques, navigation was reliable. In none of the 19 patients new postoperative neurological deficits were encountered. Intraoperative visualization of major white matter tracts allows save resection of gliomas near eloquent brain areas. A possible shifting of the pyramidal tract has to be taken into account after major tumor parts are resected. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Erlangen Nurnberg, Dept Neurosurg, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. RP Nimsky, C (reprint author), Univ Erlangen Nurnberg, Dept Neurosurg, Schwabachanlage 6, D-91054 Erlangen, Germany. EM nimsky@nch.imed.uni-erlangen.de RI Nimsky, Christopher/E-3702-2014 NR 47 TC 128 Z9 137 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2006 VL 30 IS 4 BP 1219 EP 1229 DI 10.1016/j.neuroimage.2005.11.001 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LB UT WOS:000237601500015 PM 16364659 ER PT J AU Halgren, E Wang, CM Schomer, DL Knake, S Marinkovic, K Wu, JL Ulbert, I AF Halgren, E Wang, CM Schomer, DL Knake, S Marinkovic, K Wu, JL Ulbert, I TI Processing stages uderlying word recognition in the anteroventral temporal lobe SO NEUROIMAGE LA English DT Article DE entorhinal; humans; inferotemporal; memory; perirhinal ID CURRENT-SOURCE-DENSITY; HUMAN HIPPOCAMPAL FORMATION; PERIRHINAL CORTEX; GUINEA-PIG; PARAHIPPOCAMPAL CORTICES; ENTORHINAL CORTEX; EVOKED-POTENTIALS; NEURONAL-ACTIVITY; FIELD POTENTIALS; SEMANTIC MEMORY AB The anteroventral temporal lobe integrates visual, lexical, semantic and mnestic aspects of word processing, through its reciprocal connections with the ventral visual stream, language areas, and the hippocampal formation. We used linear microelectrode arrays to probe population synaptic currents and neuronal firing in different cortical layers of the anteroventral temporal lobe, during semantic judgments with implicit priming and overt word recognition. Since different extrinsic and associative inputs preferentially target different cortical layers, this method can help reveal the sequence and nature of local processing stages at a higher resolution than was previously possible. The initial response in inferotemporal and perirhinal cortices is a brief current sink beginning at similar to 120 ms and peaking at similar to 170 ms. Localization of this initial sink to middle layers suggests that it represents feedforward input from lower visual areas, and simultaneously increased firing implies that it represents excitatory synaptic currents. Until similar to 800 ms, the main focus of transmembrane current sinks alternates between middle and superficial layers, with the superficial focus becoming increasingly dominant after similar to 550 ms. Since superficial layers are the target of local and feedback associative inputs, this suggests an alternation in predominant synaptic input between feedforward and feedback modes. Word repetition does not affect the initial perirhinal and inferotemporal middle layer sink but does decrease later activity. Entorhinal activity begins later (similar to 200 ms), with greater apparent excitatory post-synaptic currents and multiunit activity in neocortically projecting than hippocampal-projecting layers. In contrast to perirhinal and entorhinal responses, entorhinal responses are larger to repeated words during memory retrieval. These results identify a sequence of physiological activation, beginning with a sharp activation from lower level visual areas carrying specific information to middle layers. This is followed by feedback and associative interactions involving upper cortical layers, which are abbreviated to repeated words. Following bottom-up and associative stages, top-down recollective processes may be driven by entorhinal cortex. Word processing involves a systematic sequence of fast feedforward information transfer from visual areas to anteroventral temporal cortex followed by prolonged interactions of this feedforward information with local associations and feedback mnestic information from the medial temporal lobe. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92093 USA. NYU, Sch Med, Dept Neurol, Comrehens Epilespy Ctr, New York, NY 10016 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02129 USA. Univ Marburg, Dept Neurol, Marburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02129 USA. Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. RP Halgren, E (reprint author), Univ Calif San Diego, Dept Radiol, Multimodal Imaging Lab, La Jolla, CA 92093 USA. EM ehalgren@ucsd.edu RI Ulbert, Istvan/F-2213-2010 FU NINDS NIH HHS [R01 NS044623, NS44623, NS18741, R01 NS018741] NR 65 TC 47 Z9 47 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2006 VL 30 IS 4 BP 1401 EP 1413 DI 10.1016/j.neuroimage.2005.10.053 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 043LB UT WOS:000237601500032 PM 16488158 ER PT J AU Dalkara, T Zervas, NT Moskowitz, MA AF Dalkara, T Zervas, NT Moskowitz, MA TI From spreading depression to the trigeminovascular system SO NEUROLOGICAL SCIENCES LA English DT Article DE migraine; physiopathology; trigeminal nerve; neurogenic inflammation; spreading depression ID FAMILIAL HEMIPLEGIC MIGRAINE; TRANSCRANIAL MAGNETIC STIMULATION; VASCULAR HEAD PAIN; VASOGENIC LEAKAGE; EVOKED-POTENTIALS; EPISODIC ATAXIA; CEREBRAL-CORTEX; FUNCTIONAL MRI; HUMAN BRAIN; AURA AB Migraine headaches have a complex pathophysiology; both vascular and neuronal mechanisms have been proposed. One possible scenario begins with brain-initiated events evolving to cortical spreading depression (CSD), which in turn activates the trigeminal nerve to cause headaches. Experimental evidence supports a relationship between CSD as a cause of migraine aura as well as CSD as a cause of trigeminal activation. Susceptibility to CSD and to migraine appears to be genetically determined. In some migraine subtypes, genes controlling translocation of calcium, sodium and potassium have been implicated, perhaps altering the susceptibility to CSD. This chapter briefly reviews current knowledge pertaining to migraine pathophysiology with emphasis on current notions linking disturbances in ion flux to the genesis of headache. C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Univ Hacettepe, Fac Med, Dept Neurol, Ankara, Turkey. Harvard Univ, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM Moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 NR 46 TC 45 Z9 46 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1590-1874 J9 NEUROL SCI JI Neurol. Sci. PD MAY PY 2006 VL 27 SU 2 BP S86 EP S90 DI 10.1007/s10072-006-0577-z PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 042DH UT WOS:000237507200004 PM 16688636 ER PT J AU Grande, LJ Crosson, B Heilman, KM Bauer, RM Kilduff, P McGlinchey, RE AF Grande, LJ Crosson, B Heilman, KM Bauer, RM Kilduff, P McGlinchey, RE TI Visual selective attention in Parkinson's disease: Dissociation of exogenous and endogenous inhibition SO NEUROPSYCHOLOGY LA English DT Article DE inhibition of return; negative priming; bradyphrenia; subcortical connectivity; executive function ID CORTICAL GLUCOSE-METABOLISM; CHOICE REACTION-TIME; BASAL GANGLIA; INTRALAMINAR NUCLEI; RETURN; MOTOR; DEMENTIA; NEUROPATHOLOGY; INFORMATION; DYSFUNCTION AB Impairment in the inhibitory mechanism of visual selective attention in patients with Parkinson's disease (PD) is controversial. The present study sought to understand disparate findings in a manner analogous to the relative preservation of exogenously evoked movement and impairment of endogenously evoked movement. The authors examined inhibition of return (i.e., exogenously evoked inhibition; IOR) and negative priming (i.e., endogenously evoked inhibition; NP) in a group of 14 patients with PD and 14 healthy controls (HC). Unlike the HC, who demonstrated significant inhibition in both tasks, the group with PD, demonstrated intact inhibition only in the IOR task. Dopamine replacement therapy did not affect performance. The findings are discussed within the context of a model that differentiates the essential involvement of the basal ganglia for endogenously evoked spatial inhibition. C1 Harvard Univ, Sch Med, Boston VA Healthcare Syst, GRECC, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. Univ Florida, Malcolm Randall VA Med Ctr, Dept Neurol, Gainesville, FL 32611 USA. Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32611 USA. RP Grande, LJ (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, GRECC, 182-JP,150 S Huntington Ave, Boston, MA 02130 USA. EM lgrande@heartbrain.com RI Crosson, Bruce/L-3128-2013; McGlinchey, Regina/R-1971-2016 NR 74 TC 15 Z9 15 U1 1 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAY PY 2006 VL 20 IS 3 BP 370 EP 382 DI 10.1037/0894-4105.20.3.370 PG 13 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 047UN UT WOS:000237904300012 PM 16719630 ER PT J AU Tierney, TS Pradilla, G Wang, PP Clatterbuck, RE Tamargo, RJ AF Tierney, TS Pradilla, G Wang, PP Clatterbuck, RE Tamargo, RJ TI Intracranial delivery of the nitric oxide donor diethylenetriamine/nitric oxide from a controlled-release polymer: Toxicity in cynomolgus monkeys SO NEUROSURGERY LA English DT Article DE cerebral vasospasm; controlled-release preparations; diethylenetriamine/nitric oxide; Macaca fascicularis; nitric oxide; subarachnoid hemorrhage ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; INTRATHECAL SODIUM-NITROPRUSSIDE; EXPERIMENTAL CEREBRAL VASOSPASM; PHYSIOLOGICAL CONDITIONS; NONHUMAN-PRIMATES; ARTERIAL SPASM; NMDA-RECEPTOR; OXYHEMOGLOBIN; PREVENTION; REVERSAL AB OBJECTIVE: Diethylenetriamine/nitric oxide (DETA/NO) has been shown to be an effective treatment for delayed posthemorrhagic vasospasm when released abluminally from ethylene-vinyl acetate copolymer (EVAc). However, the observed mortality associated with this drug warrants further investigation. To establish a maximum tolerable dose, this study evaluated the toxicity of DETA/NO released from EVAc in a dose-escalation series in cynomolgus monkeys (Macaca fascicularis). METHODS: DETA/NO was incorporated into EVAc at a 20:80 dry weight ratio (DETA/NO:EVAc). A total of 13 animals underwent a right frontotemporal craniotomy for placement of a single polymer delivering no drug (n = 3), 0.5 +/- 0.1 mg/kg (n = 3), 0.9 +/- 0.1 mg/kg (n = 3), 1.9 +/- 0.2 mg/kg (n = 3), or a 3.2 mg/kg dose (n = 1) into the subarachnoid space. RESULTS: The animal receiving the highest dose of DETA/NO (3.2 mg/kg) died 46 hours after surgery. The remaining animals survived for the planned duration of the study. One animal in the group receiving the 1.9 mg/kg dose experienced a seizure 25 hours after surgery and remained lethargic for 2 days before making a complete recovery. The remaining animals exhibited no adverse behavioral effects. Histopathological examination of brain tissue revealed hemorrhagic and ischemic changes at doses above 0.9 mg/kg. No evidence of vascular wall pathology or infection was observed in any animal. CONCUSION: The greatest amount of DETA/NO safely delivered from EVAc copolymer to the subarachnoid space of the cynomolgus monkey is approximately 1.0 mg/kg. These findings show that continuous intracisternal delivery of DETA/NO is a safe and potentially effective strategy for prophylactic treatment of delayed cerebral vasospasm. C1 Johns Hopkins Univ, Sch Med, Dept Neurol Surg, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Tamargo, RJ (reprint author), Johns Hopkins Univ Hosp, Dept Neurol Surg, Meyer 8-181,600 N Wolfe St, Baltimore, MD 21287 USA. EM rtamarg@jhmi.edu NR 44 TC 15 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2006 VL 58 IS 5 BP 952 EP 960 DI 10.1227/01.NEU.0000210182.48546.8F PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 039IC UT WOS:000237298200039 PM 16639332 ER PT J AU Bowler, RM Koller, W Schulz, PE AF Bowler, RM Koller, W Schulz, PE TI Parkinsonism due to manganism in a welder: Neurological and neuropsychological sequelae SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT Conference on Health Effects of Manganese, Research, Industrial Hygiene and Clinical Issues in Occupational Exposures CY APR 17-18, 2004 CL New Orleans, LA SP Tulane Univ Med Sch, SAn Francisco State Univ, Assoc Occupat & Environm Clin DE manganese exposure; manganism; parkinsonism; neurological status; MRI; L-dopa; neuropsychological assessment; mood changes; motor slowing ID NERVOUS-SYSTEM; EXPOSURE; WORKERS; SERUM; UTILITY AB A 33-year-old welder with 3 years of exposure to manganese (Mn) bearing welding fumes was seen by neurologists for cognitive and motor complaints. He exhibited signs and symptoms of Parkinson's disease, including tremor, bradykinesia, gait disturbance and cogwheel rigidity. However, he was young and had significant inattention and forgetfulness, had found levodopa unhelpful and moved with a cock-walk gait, all of which suggested manganism. His serum and urine levels of Mn were, in fact, elevated, and his brain MRI had increased T1-weighted signal intensities in the basal ganglia bilaterally (globus pallidus) consistent with Mn deposition. Two years later, he underwent comprehensive neuropsychological testing. Clinical history indicated a mild tremor and emotional dysfunction with irritability, anxiety, and depression with psychotic features. He showed deficits in cognitive flexibility, information processing and speed, and greatly reduced motor speed, which are consistent with a fronto-subcortical process. These findings support a diagnosis of early onset parkinsonism from welding, (c) 2006 Elsevier Inc. All rights reserved. C1 San Francisco State Univ, San Francisco, CA 94132 USA. Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. RP Bowler, RM (reprint author), 8371 Kent Dr, El Cerrito, CA 94530 USA. EM rbowl@sfsu.edu NR 39 TC 53 Z9 55 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2006 VL 27 IS 3 BP 327 EP 332 DI 10.1016/j.neuro.2005.10.011 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 046WF UT WOS:000237841100006 PM 16457889 ER PT J AU Herbert, MR AF Herbert, MR TI Autism: Parsing heterogeneity of causes and features SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract C1 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 PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 413 EP 413 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900015 ER PT J AU Danulewicz, PA Dhillon, R Holmes, LB Adams, J AF Danulewicz, PA Dhillon, R Holmes, LB Adams, J TI Absence of neuropsychological effects following prenatal exposure to phenytoin (PHT) SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. MassGen Hosp Children, Boston, MA 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 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2006 VL 28 IS 3 BP 419 EP 419 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 056JW UT WOS:000238519900030 ER PT J AU Zhang, L Dai, WZ Nassar, R AF Zhang, L Dai, WZ Nassar, R TI A numerical method for obtaining an optimal temperature distribution in a 3-D triple-layered cylindrical skin structure embedded with a blood vessel SO NUMERICAL HEAT TRANSFER PART A-APPLICATIONS LA English DT Article ID HYPERTHERMIA; CANCER; THERAPY; HEAT AB In hyperthermia cancer treatments, the crucial problem, when heating the tumor tissue, is keeping the temperature of the normal tissue surrounding the tumor below a certain threshold so as not to cause damage to the tissue. Thus, it is important to optimize the temperature field of the entire treatment region. Recently, we have developed a numerical method for obtaining an optimal temperature distribution in a triple-layered cylindrical skin structure. In this article, we extend our method to a case involving a triple-layered cylindrical skin structure embedded with a blood vessel. The method is illustrated by a numerical example. C1 Louisiana Tech Univ, Coll Engn & Sci, Dept Math & Stat, Ruston, LA 71272 USA. Massachusetts Gen Hosp, AA Matinos Ctr Biomed Imaging, Harvard Mit Div Hlth Sci & Technol, Complex Biosyst Modeling Lab, Charlestown, MA USA. RP Dai, WZ (reprint author), Louisiana Tech Univ, Coll Engn & Sci, Dept Math & Stat, Ruston, LA 71272 USA. EM dai@coes.latech.edu NR 24 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-7782 J9 NUMER HEAT TR A-APPL JI Numer. Heat Tranf. A-Appl. PD MAY PY 2006 VL 49 IS 8 BP 765 EP 784 DI 10.1080/10407780500506691 PG 20 WC Thermodynamics; Mechanics SC Thermodynamics; Mechanics GA 035DO UT WOS:000236980600002 ER PT J AU Graf, CM AF Graf, CM TI ADN to BSN: Lessons from human capital theory SO NURSING ECONOMICS LA English DT Article ID NURSES AB Despite the recommendation by the National Advisory Council on Nurse Education and Practice to increase the percent of baccalaureate (BSN) prepared nurses in the workforce to at least two-thirds by 2010, 37% of the workforce and 60% of new grads were associates-degree (ADN) prepared as of 2000. Using the Human Capital Theory, a model was created to evaluate if increases in earnings achieved by ADNs when they earned a higher degree outweighed the cost of their education. ADNs who earn their BSN do, in fact, earn a significant annual wage premium. However, after projecting net lifetime earnings and an internal rate of return (IRR), the model revealed that for more than half of the ADN-to-BSN graduates, the costs of education were greater than the salary increase. Younger nurses were more likely to experience a positive IRR due to the longer term of the investment, and were nearly four times as likely to pursue an advanced degree with a positive expected IRR. Employers who encourage BSN completion early in the career trajectory and provide tuition support will be better able to demonstrate a positive rate of return and influence the choice to pursue higher education. C1 Massachusetts Gen Hosp, Patient Care Serv Management Syst, Boston, MA 02114 USA. RP Graf, CM (reprint author), Massachusetts Gen Hosp, Patient Care Serv Management Syst, Boston, MA 02114 USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD MAY-JUN PY 2006 VL 24 IS 3 BP 135 EP 141 PG 7 WC Nursing SC Nursing GA 050KK UT WOS:000238086100004 PM 16786828 ER PT J AU Robbins, LB Gretebeck, KA Kazanis, AS Pender, NJ AF Robbins, LB Gretebeck, KA Kazanis, AS Pender, NJ TI Girls on the move program to increase physical activity participation SO NURSING RESEARCH LA English DT Article DE female adolescents; intervention; physical activity ID ADOLESCENT GIRLS; PRIMARY-CARE; SEDENTARY BEHAVIORS; AFRICAN-AMERICAN; SELF-EFFICACY; WHITE GIRLS; OBESITY; QUESTIONNAIRES; VALIDATION; OVERWEIGHT AB Background: Because physical inactivity poses serious health risks, interventions are urgently needed to reverse the increasingly sedentary lifestyles of adolescent girls. Objective: The aim of this study was to determine the feasibility of "Girls on the Move," an individually tailored computerized physical activity (PA) program plus nurse counseling intervention, in increasing PA. Methods: A pretest-posttest control group design was used with 77 racially diverse sedentary girls in Grades 6, 7, and 8 from two middle schools. Each of the instructional grades was randomly assigned to either an intervention or control condition. After completing computerized questionnaires, each girl in the control group received a handout listing the PA recommendations. To encourage PA, each girl in the intervention group received computerized, individually tailored feedback messages based on her responses to the questionnaires, individual counseling from the school's pediatric nurse practitioner (PNP), and telephone calls and mailings from a trained research assistant. At 12 weeks, girls in both groups responded to the questionnaires. Results: No differences in self-reported PA emerged between the intervention and control groups at Weeks 1 (baseline) and 12 (postintervention). Repeated measures ANOVA showed a significant interaction between group and time for social support for PA, F(1, 69) = 5.73, p = .019, indicating that the intervention group had significantly greater social support across time than did the control group. From baseline to postintervention, social support increased for the intervention group but decreased for the control group. Discussion: Reasons for the lack of significant differences between the groups on the PA measures were cited. Important information that could inform subsequent studies that test interventions to increase youth PA was acquired from conducting this study. Future efforts to increase PA participation might include this approach for enhancing social support for PA. C1 Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. US Dept Vet Affairs, Ann Arbor, MI USA. RP Robbins, LB (reprint author), Michigan State Univ, Coll Nursing, A203 Life Sci, E Lansing, MI 48824 USA. EM robbin76@msu.edu NR 45 TC 46 Z9 47 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAY-JUN PY 2006 VL 55 IS 3 BP 206 EP 216 DI 10.1097/00006199-200605000-00007 PG 11 WC Nursing SC Nursing GA 046WI UT WOS:000237841400007 PM 16708045 ER PT J AU King, DE Mainous, AG Geesey, ME Egan, BM Rehman, S AF King, Dana E. Mainous, Arch G., III Geesey, Mark E. Egan, Brent M. Rehman, Shakeib TI Magnesium supplement intake and C-reactive protein levels in adults SO NUTRITION RESEARCH LA English DT Article DE magnesium; C-reactive protein; diet; supplement; inflammation; adult ID METABOLIC SYNDROME; CHOLESTEROL; ATHEROSCLEROSIS; INFLAMMATION; DISEASE; HEALTH; RISK; CARE AB Previous research has indicated that dietary magnesium may be a key component in the association between diet and inflammation; however, the role of intake from magnesium supplements has not been elucidated. The objective of this study was to determine the likelihood of elevated C-reactive protein (CRP) in people taking magnesium-containing supplements of 50 mg/d or more. We examined this issue in a study sample derived from the National Health and Nutrition Examination Survey 1999-2002, a nationally representative, survey of the civilian, noninstitutionalized population of the United States. Among US adults, 25.6% were taking a magnesium supplement of at least 50 mg daily. Only 21.9% of individuals not taking supplemental magnesium met or exceeded the recommended daily allowances (RDA) for magnesium intake compared with 60.2% of adults who were taking magnesium supplements. In adjusted logistic regression analyses, people whose total daily magnesium intake was below the RDA were significantly 40% more likely to have elevated CRP regardless of whether they were taking magnesium supplements (P < .05). Among people with dietary magnesium intake less than 50% RDA, individuals taking magnesium supplements were 22% less likely to have elevated CRP. Magnesium supplement intake is associated with a lower likelihood of elevated CRP in people with low dietary magnesium intake. Prospective studies are needed to examine whether magnesium supplementation can reduce levels of CRP. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Family Med, Charleston, SC 29464 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29464 USA. Ralph H Johnson VA Med Ctr, Dept Med, Charleston, SC 29403 USA. RP King, DE (reprint author), Med Univ S Carolina, Dept Family Med, Charleston, SC 29464 USA. EM kingde@musc.edu OI King, Dana/0000-0001-5494-3467; Mainous, Arch/0000-0002-2535-7685 NR 18 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 2006 VL 26 IS 5 BP 193 EP 196 DI 10.1016/j.nutres.2006.05.001 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 073BA UT WOS:000239716100001 ER PT J AU Wadden, TA West, DS Delahanty, LM Jakicic, JM Rejeski, WJ Berkowitz, RI Williamson, DA Kelley, DE Kumanyika, SK Hill, JO Tomchee, CM Armstrong, N Bantle, J Bolin, P Cerniauskas, B Foreyt, J Gregg, E Kuczmarski, R Miller, M Mobley, C Obarzanek, E Otto, A Pal, C Reeves, R Vitolins, M Wing, R Yanovski, S AF Wadden, Thomas A. West, Delia Smith Delahanty, Linda M. Jakicic, John M. Rejeski, W. Jack Berkowitz, Robert I. Williamson, Donald A. Kelley, David E. Kumanyika, Shiriki K. Hill, James O. Tomchee, Christine M. Armstrong, Nell Bantle, John Bolin, Paula Cerniauskas, Barbara Foreyt, John Gregg, Edward Kuczmarski, Robert Miller, Marsha Mobley, Connie Obarzanek, Eva Otto, Amy Pal, Carmen Reeves, Rebecca Vitolins, Mara Wing, Rena Yanovski, Susan TI The Look AHEAD Study: A description of the lifestyle intervention and the evidence supporting it SO OBESITY LA English DT Review DE weight loss; diet; physical activity; lifestyle modification; weight maintenance ID RANDOMIZED CONTROLLED-TRIAL; LOW-CALORIE DIET; IMPAIRED GLUCOSE-TOLERANCE; PLACEBO-CONTROLLED TRIAL; WEIGHT-CONTROL PROGRAM; LONG-TERM MANAGEMENT; OBESE NIDDM PATIENTS; PHYSICAL-ACTIVITY; CARDIORESPIRATORY FITNESS; AEROBIC EXERCISE AB The Look AHEAD (Action for Health in Diabetes) study is a multicenter, randomized controlled trial designed to determine whether intentional weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. The study began in 2001 and is scheduled to conclude in 2012. A total of 5145 participants have been randomly assigned to a lifestyle intervention or to an enhanced usual care condition (i.e., diabetes support and education). This article describes the lifestyle intervention and the empirical evidence to support it. The two principal intervention goals are to induce a mean loss >= 7% of initial weight and to increase participants' moderately intense physical activity to >= 175 min/wk. For the first 6 months, participants attend one individual and three group sessions per month and are encouraged to replace two meals and one snack a day with liquid shakes and meal bars. From months 7 to 12, they attend one individual and two group meetings per month and continue to replace one meal per day (which is recommended for the study's duration). Starting at month 7, more intensive behavioral interventions and weight loss medication are available from a toolbox, designed to help participants with limited weight loss. In Years 2 to 4, treatment is provided mainly on an individual basis and includes at least one on-site visit per month and a second contact by telephone, mail, or e-mail. After Year 4, participants are offered monthly individual visits. The intervention is delivered by a multidisciplinary team that includes medical staff who monitor participants at risk of hypoglycemic episodes. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Massachusetts Gen Hosp, Boston Harvard Ctr, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Brown Univ, Providence, RI 02912 USA. RP Wadden, TA (reprint author), Univ Penn, Sch Med, 3535 Market St, Philadelphia, PA 19104 USA. EM wadden@mail.med.upenn.edu NR 87 TC 209 Z9 209 U1 5 U2 29 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD MAY PY 2006 VL 14 IS 5 BP 737 EP 752 PG 16 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 066SF UT WOS:000239249700001 ER PT J AU Meigs, JB Dupuis, J Liu, CY O'Donnell, CJ Fox, CS Kathiresan, S Gabriel, SB Larson, MG Yang, Q Herbert, AG Wilson, PWF Feng, DL Tofler, GH Cupples, LA AF Meigs, James B. Dupuis, Josee Liu, Chunyu O'Donnell, Christopher J. Fox, Caroline S. Kathiresan, Sekar Gabriel, Stacey B. Larson, Martin G. Yang, Qiong Herbert, Alan G. Wilson, Peter W. F. Feng, DaLi Tofler, Geoffrey H. Cupples, L. Adrienne TI PAI-1 gene 4G/5G polymorphism and risk of type 2 diabetes in a population-based sample SO OBESITY LA English DT Article DE type 2 diabetes; insulin; genetics; risk factors; longitudinal study ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSULIN-RESISTANCE ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; PROMOTER; ASSOCIATION; HISPANICS; MELLITUS; PROTEINS; GENOTYPE; DISEASE AB Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) increase risk for type 2 diabetes. The PAI-1 4G/5G polymorphism is a major genetic determinant of plasma PAI-1 levels, with 4G/4G homozygotes having elevated PAI-1 levels relative to 5G allele carriers. These observations suggest the hypothesis that the PAI-1 4G/5G polymorphism could be a genetic risk factor for diabetes. We tested this hypothesis among 2169 participants of the Framingham Offspring Study followed for seven examinations over 26 years for 216 cases of type 2 diabetes. PAI-1 4G/4G homozygotes (genotype frequency, 27.4%) were not at significantly (p > 0.05) increased risk of incident diabetes compared with 5G allele carriers and did not have elevated levels of diabetes-related quantitative traits including BMI, fasting plasma glucose, or fasting insulin. In proportional hazards regression models accounting for correlation among siblings, with the 5G/5G genotype as the referent, the hazard ratio for incident diabetes for 4G/5G carriers was 0.93 (95% confidence interval, 0.68 to 1.28) and for 4G/4G carriers was 1.20 (95% confidence interval, 0.83 to 1.92). Results were not altered by further adjustment for sex or levels of BMI, triglycerides, or PAI-1. We conclude that the PAI-1 4G/5G polymorphism is not an important genetic, risk factor for type 2 diabetes in this community-based sample. Elevated PAI-1 levels may be associated with an increased risk for diabetes as a marker for underlying endothelial dysfunction rather than by a direct effect of genetically mediated elevated levels. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. Mayo Clin, Div Cardiol, Rochester, MN USA. Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org RI Yang, Qiong/G-5438-2014 FU NHLBI NIH HHS [R01 HL48157, N01-HC-25195, R01 HL76784] NR 25 TC 15 Z9 16 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBESITY JI Obesity PD MAY PY 2006 VL 14 IS 5 BP 753 EP 758 DI 10.1038/oby.2006.85 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 066SF UT WOS:000239249700002 PM 16855181 ER PT J AU Zuckerman, D Seliem, R Hochberg, E AF Zuckerman, Dan Seliem, Rania Hochberg, Ephraim TI Intravascular lymphoma: The oncologist's "great imitator" SO ONCOLOGIST LA English DT Article ID LARGE-CELL LYMPHOMA; MALIGNANT ANGIOENDOTHELIOMATOSIS; NEUROLOGIC MANIFESTATIONS; ADHESION MOLECULES; HOMING RECEPTORS; UNKNOWN ORIGIN; ASIAN VARIANT; TRANSPLANTATION; CHEMOTHERAPY; ANTIBODIES AB Intravascular lymphoma (IVL) is a rare subtype of extranodal diffuse large B-cell lymphoma with a distinct presentation. Anatomically the disease is characterized by the proliferation of clonal lymphocytes within small vessels with relative sparing of the surrounding tissue. The clinical symptoms of the disease are dependent on the specific organ involvement, which most often includes the central nervous system and skin. Because of the various modes of presentation and the rarity of IVL, the diagnosis is often made postmortem. The diagnosis is almost exclusively made by surgical biopsy of a suspected site of involvement. Advances in imaging and immunohistochemistry have led to increasing antemortem diagnosis of this lymphoma. Although some patients with this disease may be curable with aggressive therapy, further research into novel treatment strategies is needed to improve outcome. Some potential insights into future therapies may be drawn from the small amount of basic science literature relevant to this entity. This review provides a concise, up-to-date summary of IVL. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Zuckerman, D (reprint author), Ctr Hematol, 55 Fruit St,Yawkey Bldg,7E-7700, Boston, MA 02114 USA. EM dszuckerman@partners.org NR 53 TC 80 Z9 85 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2006 VL 11 IS 5 BP 496 EP 502 DI 10.1634/theoncologist.11-5-496 PG 7 WC Oncology SC Oncology GA 085TM UT WOS:000240627300009 PM 16720850 ER PT J AU Penson, RT Kyriakou, H Zuckerman, D Chabner, BA Lynch, TJ AF Penson, Richard T. Kyriakou, Helena Zuckerman, Dan Chabner, Bruce A. Lynch, Thomas J., Jr. TI Teams: Communication in multidisciplinary care SO ONCOLOGIST LA English DT Article DE oncology; support; psychosocial; cancer ID ONCOLOGY AB Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital (MGH),founded The Kenneth B. Schwartz Center at MGH. The Schwartz Center is a nonprofit organization dedicated to supporting and advancing compassionate health care delivery that provides hope to the patient and support to caregivers, and encourages the healing process. The Center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members. The evolving field of oncology increasingly requires a team of medical specialists working in unison to deliver optimal medical care. While this coordination may maximize the technical synergy of care, it can challenge interprofessional and interdisciplinary connections. Poor and miscommunication and conflicts between staff and between the family and providers adversely affect patient care and quality of life. Furthermore, lack of communication leaves a vacuum that sucks in fear. A recent Newsweek article highlighted the challenges of practicing in the age of high-tech medicine. The author had to beg for a prognosis for her critically ill and dying husband, with unhelpful subspecialists failing to communicate the bigger picture. This article explores the tough issue of how teams handle uncertainty and bad news and how patients and families can be better supported in the multifaceted paradigm of modern care. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Kenneth B Schwartz Ctr, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Kenneth B Schwartz Ctr, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 22 TC 21 Z9 22 U1 3 U2 13 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2006 VL 11 IS 5 BP 520 EP 526 DI 10.1634/theoncologist.11-5-520 PG 7 WC Oncology SC Oncology GA 085TM UT WOS:000240627300011 PM 16720852 ER PT J AU Richardson, P AF Richardson, P TI Newer treatment options for patients in first relapse - From the multiple myeloma research foundation SO ONCOLOGY-NEW YORK LA English DT Article ID REFRACTORY MYELOMA; BORTEZOMIB; PHASE-2; TRANSPLANTATION; MULTICENTER; COMBINATION; THERAPY; MM AB Treatment regimens for multiple myeloma are evolving because of new advances in both pharmacotherapy and transplantation strategies. The Multiple Myeloma Research Foundation (MMRF) has the top thought leaders in myeloma - research to prepare an engaging, interactive series of case studies in multiple myeloma, which are available online at www.multiplemyeloma.org, and will be published on a regular basis in ONCOLOGY. information about the interactive series, see the MMRF ad on page 642. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Richardson, P (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 9 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 MAY PY 2006 VL 20 IS 6 BP 633 EP 638 PG 6 WC Oncology SC Oncology GA 052FG UT WOS:000238216400013 PM 16773847 ER PT J AU Bauer-Wu, S AF Bauer-Wu, S TI Here for now: Living well with cancer through mindfulness. SO ONCOLOGY NURSING FORUM LA English DT Book Review C1 Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. RP Bauer-Wu, S (reprint author), Dana Farber Canc Inst, Nursing Serv, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 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 MAY PY 2006 VL 33 IS 3 BP 658 EP 658 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 047IW UT WOS:000237874000025 ER PT J AU Bernardino, CR Mihora, LD Fay, AM Rubin, PAD AF Bernardino, CR Mihora, LD Fay, AM Rubin, PAD TI Orbital complications of hydrogel scleral buckles SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID LONG-TERM COMPLICATIONS; RETINAL REATTACHMENT SURGERY; FRAGMENTATION; SILICONE; MIRAGEL; REMOVAL AB Purpose: Hydrogel is a biocompatible osmotic expansile material used in contact lenses, scleral buckles, and orbital expanders. Three unique complications from hydrogel scleral buckle use are presented: orbital cellulitis mimicry, fornical shortening with orbital prosthetic intolerance, and orbital pseudotumor. Methods: A retrospective chart review was conducted on three subjects with unknown hydrogel scleral buckle complications at a tertiary care oculoplastics practice. Demographics, imaging studies, and pathologic specimens were reviewed. Results: All three patients had a history of encircling hydrogel scleral buckle placed for retinal detachment. The mean time from implantation to presentation was 10.7 years (range, 7 to 15 years). One patient had an onset of presumed orbital cellulitis caused by an enlarged buckle and no abscess. The second patient had inability to wear an evisceration prosthesis as the result of a shortened fornix from an enlarged hydrogel scleral buckle implant. The third patient presented with an orbital mass caused by the enlarged implant. In all cases, surgical removal of the expanded buckle relieved the patient's symptoms. Conclusions: Although the hydrogel scleral band is designed to expand in a controlled fashion, overexpansion can occur. Expansion can cause buckle extrusion, prosthetic intolerance, a pseudo-orbital cellulitis, or orbital pseudotumor and may be due to a chemical change in the hydrogel polymer. Patients with hydrogel scleral buckles should be followed long-term for possible complications. Patients with newer uses of hydrogel, such as orbital expanders, should also be observed for long-term complications. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Emory Eye Ctr, Dept Oculoplast, Atlanta, GA USA. Univ Tennessee, Dept Ophthalmol, Chattanooga Unit, Chattanooga, TN USA. RP Bernardino, CR (reprint author), Emory Eye Clin, 1365B Clifton Rd NE, Atlanta, GA 30322 USA. EM crbernardino@mac.com NR 11 TC 10 Z9 11 U1 0 U2 0 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 MAY-JUN PY 2006 VL 22 IS 3 BP 206 EP 208 DI 10.1097/01.iop.0000214489.45506.87 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 045WG UT WOS:000237772800012 PM 16714931 ER PT J AU Chow, SP Aiello, LM Cavallerano, JD Katalinic, P Hock, K Tolson, A Kirby, R Bursell, SE Aiello, LP AF Chow, SP Aiello, LM Cavallerano, JD Katalinic, P Hock, K Tolson, A Kirby, R Bursell, SE Aiello, LP TI Comparison of nonmydriatic digital retinal imaging versus dilated ophthalmic examination for nondiabletic eye disease in persons with diabetes SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID RETINOPATHY; PROGRAM AB Objective: To evaluate the ability of stereoscopic nonmydriatic digital retinal imaging to detect ocular pathologic features other than diabetic retinopathy (DR) in patients with diabetes mellitus (DM) compared with dilated retinal examination by retinal specialist ophthalmologists. Design: Clinic-based comparative instrument study and retrospective chart review. Participants: Two hundred eighty Joslin Diabetes Center outpatients (560 eyes) with type 1 or type 2 DM. Methods: Nonsimultaneous stereoscopic nonmydriatic digital retinal images (640 X 480 pixels) of three 45 degrees retinal fields were acquired and graded for clinical level of DR and other ocular pathologic features by certified readers according to Joslin Vision Network (JVN) protocol. Retrospective chart review compared findings from JVN digital images with findings from dilated retinal examination by retinal specialists performed within an average of 39.6 days of digital imaging. An independent senior retinal specialist adjudicated disagreements by review of 7 standard field 35-mm Early Treatment Diabetic Retinopathy Study protocol fundus photographs and JVN images. Main Outcome Measures: Detection of non-DR ocular pathologic features by digital imaging as compared with clinical examination. Results: Nonmydriatic digital evaluation identified at least 1 non-DR ocular finding in 40.7% of patients (114/280). Non-diabetes mellitus ocular pathologic features identified by digital images, clinical examination, or both included cataract (n = 100); age-related maculopathy (n = 52); suspicion of glaucoma (n = 18); choroidal lesions (n = 18); evidence of systemic disorder (e.g., hypertension or renal disease; n = 15); epiretinal membrane (n = 11); chorioretinal atrophy, scar, or both (n = 6); retinal emboli (n = 3); retinitis pigmentosa (n = 1); and asteroid hyalosis (n = 1). Agreement of nonmydriatic imaging with clinical examination for presence and absence of these findings was 95.4%, 91.3%, 98.2%, 98.6%, 98.2%, 99.6%, 100%, 100%, 100%, and 100%, respectively. kappa Values for all non-DR lesions demonstrated near perfect agreement (kappa >= 0.80) except for age-related maculopathy (kappa = 0.71) and choroidal lesions (kappa = 0.73), where agreement was substantial. Overall, only 55 eyes (9.8%) were ungradable for level of DR and 85 eyes (15.2 %) were ungradable for macular edema. Conclusions: Joslin Vision Network nonmydriatic digital imaging demonstrated excellent agreement with dilated ophthalmic examination by retinal specialists in the detection of ocular disease other than DR, suggesting a potential role for this technology in evaluating non-DR disorders and highlighting the extent of findings other than retinopathy in patients with diabetes. C1 Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. Joslin Diabet Ctr, Sect Eye Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Beetham Eye Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM M.Aiello@joslin.harvard.edu NR 22 TC 30 Z9 30 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2006 VL 113 IS 5 BP 833 EP 840 DI 10.1016/j.ophtha.2005.12.025 PG 8 WC Ophthalmology SC Ophthalmology GA 038XQ UT WOS:000237263200019 PM 16650680 ER PT J AU Scully, C Sonis, S Diz, PD AF Scully, C Sonis, S Diz, PD TI Oral mucositis SO ORAL DISEASES LA English DT Review DE mucositis; oral; radiotherapy; chemotherapy; cancer ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; CHEMOTHERAPY-INDUCED MUCOSITIS; NECK-CANCER-PATIENTS; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; DOUBLE-BLIND TRIAL; RANDOMIZED CONTROLLED-TRIAL; RADIATION-INDUCED MUCOSITIS; REGIMEN-RELATED TOXICITIES AB Mucositis and xerostomia are the most common oral complications of the non-surgical therapy of cancer. Mucositis, a common sequel of radio- (DXR), chemo-(CXR) and radiochemo-therapy in patients with cancer, or patients requiring haemopoietic stem cell transplants (HSCT), has a direct and significant impact on the quality of life and cost of care, and also affects survival - because of the risk of infection. Apart from dose reduction, preventive and treatment options for mucositis are scarce, although multiple agents have been tested. Evidence suggests that cryotherapy, topical benzydamine and amifostine might provide some benefit in specific situations. The recombinant human keratinocyte growth factor Palifermin (Kepivance((R))) was recently approved as a mucositis intervention in patients receiving conditioning regimens before HSCT for the treatment of haematological malignancies. A number of mechanistically based interventions are in various stages of development. Unfortunately, many other approaches have not been rigorously tested. This paper reviews the clinical features, prevalence, diagnosis, complications, pathogenesis, prophylaxis and management of mucositis. C1 Univ London, Univ Coll London, Eastman Dent Inst, London WC1X 8LD, England. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Oral Med & Diagnost Sci,Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Oral Med & Diagnost Sci,Div Dent, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Oral Med & Diagnost Sci, Div Oral & Maxillofacial Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Santiago de Compostela, Sch Med & Dent, Special Needs Unit, Santiago De Compostela, Spain. RP Scully, C (reprint author), Univ London, Univ Coll London, Eastman Dent Inst, 256 Grays Inn Rd, London WC1X 8LD, England. EM c.scully@eastman.ucl.ac.uk NR 180 TC 113 Z9 120 U1 4 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1354-523X J9 ORAL DIS JI Oral Dis. PD MAY PY 2006 VL 12 IS 3 BP 229 EP 241 DI 10.1111/j.1601-0825.02006.01258.x PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 042GD UT WOS:000237515000003 PM 16700732 ER PT J AU Solomon, DH Finkelstein, JS Polinski, JM Arnold, M Licari, A Cabral, D Canning, C Avorn, J Katz, JN AF Solomon, DH Finkelstein, JS Polinski, JM Arnold, M Licari, A Cabral, D Canning, C Avorn, J Katz, JN TI A randomized controlled trial of mailed osteoporosis education to older adults SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE education; older adults; public health ID HORMONE REPLACEMENT THERAPY; INTERVENTIONS; FRACTURE; GUIDELINES; PATTERNS; RATES AB Introduction: Osteoporosis represents a growing public health concern; however, current rates of management are sub-optimal. The aim of our study was to assess, in a randomized controlled trial, the effect of a mailed educational intervention on older adults' knowledge, attitudes, and preventive behaviors regarding osteoporosis. The setting was a large publicly funded state pharmacy benefits program. The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people. Methods: All women aged over 65 years, and all men and women with a history of fracture or long-term oral use of glucocorticoid, were included. Approximately half of the participants (intervention group) were randomly selected to receive three mailings aimed at improving knowledge of osteoporosis and enhancing preventive activities, such as using calcium and vitamin D, reducing fall risks in the home, obtaining a bone mineral density (BMD) test, and taking medications when necessary. The other participants did not receive the intervention mailings and served as controls. We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge, attitudes, self-efficacy (confidence in one's ability to perform specific activities), and behavior regarding osteoporosis prevention and treatment. Six hundred randomly selected participants in the intervention group and an equal number in the control group were invited to participate. Results: Twenty-six had died and 636 of the remaining 1,185 (54%) completed the survey. Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors. All scales had good reliability (all Cronbach's alphas > 0.65). Knowledge of osteoporosis was generally very good and did not differ between intervention (mean = 65% correct responses) and control subjects (mean = 67% correct; P=0.4). Perceived susceptibility to osteoporosis was relatively high and similar across groups (P=0.4). Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention (mean = 4.3 on a 0-5 scale) and control (mean = 4.2, P=0.03) groups . On average, subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group (P=0.5). Conclusions: Compared with the controls, a mailed educational intervention for osteoporosis was not associated with better knowledge, higher perceived susceptibility, or performance of preventive measures among the at-risk older adults that we studied. The intervention group demonstrated a small increase in self-efficacy. More intensive patient interventions or intervention aimed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol, Boston, MA 02120 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Solomon, DH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org FU NIAMS NIH HHS [K23 AR48616, K24 AR02123, P60 AR47782, R55 AR48264]; NIDA NIH HHS [R01 DA15507]; NIDDK NIH HHS [K24 DK02759] NR 16 TC 40 Z9 46 U1 0 U2 3 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2006 VL 17 IS 5 BP 760 EP 767 DI 10.1007/s00198-005-0049-y PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 033EO UT WOS:000236829600014 PM 16432644 ER PT J AU Mankarious, LA Pires, VL Rudnick, JA AF Mankarious, LA Pires, VL Rudnick, JA TI Local control of murine subglottis development SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 27-30, 2005 CL Las Vegas, NV SP Amer Soc Pediat Otolaryngol ID STENOSIS; INJURY AB OBJECTIVE: To determine if subglottic development is at least partially under local control and to determine which tissue layer(s) is predominantly responsible. DESIGN: The suglottises of 12 day-3 CD1 mice were grown in whole organ Culture. The 12 subglottises were divided into 3 individual groups: + + + +, and - - -. Group +++ had all tissue layers of the subglottis intact: luminal epithelium, cricoid cartilage, inner and outer perichondrium. Group - + + had all layers intact with the exception of luminal epithelium. Group - - - had all layers removed (luminal epithelium, inner and outer perichondrium) resulting in cricoid cartilage-only rings. All ring s were grown in basic medium without the use of growth factors or serum for 15 days. Measurements of the rings were taken before and after organ Culture growth. RESULTS: Group +++ was the only group that experienced growth. only luminal growth was statistically significant although all rings experienced growth in both the luminal and external diameter. Group - + + did not experience any growth. Group - - lost structural integrity with collapse of the ring and did not experience growth of any dimension of the cartilage. CONCLUSIONS: Growth of the subglottis is under local control but may have additional influences from the Outside that were not investigated here. Removal of just the epithelium Stunts growth of the entire ring, but preferentially the lumen more so than the external diameter. Removal of all tissue layers around the cricoid cartilage results in a structural collapse of the ring, suggesting that the cartilage in this age group is dependent on surrounding tissues for structural integrity. (C) 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM leila_mankarious@meei.harvard.edu FU PHS HHS [5K08HLL70116-03] NR 5 TC 7 Z9 7 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 MAY PY 2006 VL 134 IS 5 BP 843 EP 847 DI 10.1016/j.otohns.2005.12.023 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 039ZH UT WOS:000237347200024 PM 16647545 ER PT J AU Harthorne, JW AF Harthorne, JW TI Special tribute to Seymour Furman, MD 1931-2006 SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Harthorne, JW (reprint author), Massachusetts Gen Hosp, Cardiac Unit, 55 Fruit St, Boston, MA 02114 USA. EM Harthorne.John@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAY PY 2006 VL 29 IS 5 BP 450 EP 450 DI 10.1111/j.1540-8159.2006.00397.x PG 1 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 040BE UT WOS:000237353200003 PM 16689835 ER PT J AU Sitzman, BT Gallagher, RM AF Sitzman, BT Gallagher, RM TI Effectiveness of electrical neuromodulation: An economic paradigm SO PAIN MEDICINE LA English DT Article DE electrical neuromodulation; cost; economic; effectiveness; efficacy ID SPINAL-CORD STIMULATION; COST-EFFECTIVENESS ANALYSIS; CHRONIC PAIN AB The last 10-15 years has witnessed a rapid growth and advancement of electrical neuromodulation technologies: spinal cord stimulation, peripheral nerve stimulation, deep brain stimulation, and motor cortex stimulation. As the manuscripts in this Pain Medicine supplement attest, there is strong evidence documenting the efficacy and safety of electrical neuromodulation in the treatment of many chronic, refractory pain conditions, including complex regional pain syndromes, intractable angina pectoris, neuropathic extremity pain, axial low back pain, atypical facial pain, certain visceral pain syndromes, and others. Along with the growth in utilization of electrical neuromodulation therapies, competitive pressures within the healthcare industry have created the need for other healthcare decision makers, specifically the government and third-party insurance payers, to examine the overall effectiveness and costs of electrical neuromodulation. Our objective was not to summarize the results of cost analysis studies involving neuromodulation. Doing so would be relatively simple. It is more important for the clinician to understand the underlying problems in our current reimbursement system. In doing so, we as physicians can better understand the true "value" of electrical neuromodulation therapy from the perspectives of the individual patient, the hospital administrator, and the healthcare payer. C1 Forrest Gen Canc Ctr, Hattiesburg, MS 39401 USA. Univ Penn, Sch Med, Dept Psychiat, Ctr Pain Med Res & Policy, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Sitzman, BT (reprint author), Forrest Gen Canc Ctr, 301 S 28th Ave, Hattiesburg, MS 39401 USA. EM toddsitzman@msn.com NR 6 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAY PY 2006 VL 7 SU 1 BP S185 EP S190 DI 10.1111/j.1526-4637.2006.00133.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 030YY UT WOS:000236672500020 ER PT J AU Wang, YL Hu, R Lugea, A Gukovsky, I Smoot, D Gukovskaya, AS Pandol, SJ AF Wang, Yan-Ling Hu, Richard Lugea, Aurelia Gukovsky, Ilya Smoot, Duane Gukovskaya, Anna S. Pandol, Stephen J. TI Ethanol feeding alters death signaling in the pancreas SO PANCREAS LA English DT Article DE ethanol; apoptosis; necrosis; signal transduction ID NECROTIC CELL-DEATH; INDUCED LIVER APOPTOSIS; KAPPA-B ACTIVATION; ACINAR-CELLS; CATHEPSIN-B; TRYPSINOGEN ACTIVATION; MITOCHONDRIAL DYSFUNCTION; TRANSCRIPTION FACTORS; STAT PROTEINS; IFN-GAMMA AB Objectives: Alcohol abuse is a major cause of pancreatitis, which is associated with death of parenchymal cells. The goal of this study was to explore the effects of ethanol on cell death pathways in the pancreas. Methods: Adult male Wistar rats were fed with ethanol diets using the Lieber-DeCarli method. Caspase-8, caspase-3, and cathepsin B expression and activity in the pancreas of these animals as well as the signals that regulate their expression were studied using Western blot analysis and specific assays for biochemical enzyme activity. Results: In the pancreas from rats fed with ethanol, the protein expression and activity of caspase-8 decreased by 48% and 45%, respectively, and caspase-3 activity decreased by 39%. In contrast, cathepsin B protein expression and activity increased with ethanol feeding by 189% and 143%, respectively. Evaluation of the transcriptional regulatory system for caspase-8 and cathepsin B showed that the ethanol effects on these pathways were largely transcriptional. Conclusions: Our findings show effects of ethanol on the expression of several signals involved in cell death in the pancreas through alteration of transcriptional regulators. The decrease in caspase expression and increase in cathepsin B expression indicate that ethanol feeding may prevent apoptosis and promote necrosis of pancreatic tissue with stresses that cause pancreatitis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. Howard Univ, Sch Med, Washington, DC 20059 USA. RP Pandol, SJ (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 258,Room 340, Los Angeles, CA 90073 USA. EM Stephen.pandol@med.va.gov FU NIAAA NIH HHS [1 U56 AA0114643, T32 AA07578]; NIDDK NIH HHS [DK-59508] NR 70 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD MAY PY 2006 VL 32 IS 4 BP 351 EP 359 DI 10.1097/01.mpa.0000220859.93496.e1 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101AJ UT WOS:000241711000004 PM 16670617 ER PT J AU Jahraus, CD Tarbell, NJ AF Jahraus, CD Tarbell, NJ TI Optic pathway gliomas SO PEDIATRIC BLOOD & CANCER LA English DT Review DE chemotherapy; Moyamoya disease; optic pathway glioma; pediatric; radiotherapy; surgery ID LOW-GRADE GLIOMAS; OF-THE-LITERATURE; TERM-FOLLOW-UP; RADIATION-THERAPY; HYPOTHALAMIC GLIOMAS; LONG-TERM; NEUROFIBROMATOSIS TYPE-1; RECKLINGHAUSENS-DISEASE; PILOCYTIC ASTROCYTOMAS; RADIOGRAPHIC RESPONSE AB Optic pathway gliomas represent approximately 5% of all pediatric intracranial tumors. While these tumors are most frequently low grade astrocytomas, they follow a highly variable clinical Course, and accordingly, there is Much debate regarding their optimal management. Their propensity to Occur ill very Young children and infants further complicates selection of therapy. Historically, surgery and radiotherapy have played a primary role in management, however, in the last 15 years, chemotherapy has evolved into the first-line treatment of choice. Nonetheless, chemotherapy frequently fails, but serves to delay implementation of radiotherapy Or Surgery until the child has progressed neuropsychologically. An overall favorable prognosis for this tumor emphasizes the need for careful selection of therapy. Herein, we review the major features of optic pathway glioma, including epidemiology, pathology, therapeutic interventions, outcome, and treatment sequelae. C1 Univ Alabama, Dept Radiat Oncol, Lurleen B Wallace Tumor Inst 123, Birmingham, AL 35249 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Jahraus, CD (reprint author), Univ Alabama, Dept Radiat Oncol, Lurleen B Wallace Tumor Inst 123, 619 19th St S, Birmingham, AL 35249 USA. EM cjahraus@uabmc.edu OI Jahraus, Christopher/0000-0002-2013-479X NR 108 TC 52 Z9 53 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY 1 PY 2006 VL 46 IS 5 BP 586 EP 596 DI 10.1002/pbc.20655 PG 11 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 029CX UT WOS:000236536900010 PM 16411210 ER PT J AU Lee, P Westra, S Baba, T McCauley, R AF Lee, P Westra, S Baba, T McCauley, R TI Right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus SO PEDIATRIC RADIOLOGY LA English DT Article DE pulmonary aplasia; pulmonary agenesis; aberrant pulmonary artery; pulmonary sling; bronchopulmonary sequestration; bronchopulmonary foregut malformation; esophageal bronchus ID AGENESIS; ANOMALIES; LUNG AB Pulmonary aplasia and bronchopulmonary foregut malformations in which a patent communication between the foregut and the pulmonary system is present are rare congenital abnormalities. Pulmonary aplasia associated with a pulmonary sling is an even rarer abnormality. We report a unique case of right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus diagnosed by multidetector helical CT. C1 Tufts Univ, New England Med Ctr, Dept Radiol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Pediat, Boston, MA 02111 USA. RP McCauley, R (reprint author), Tufts Univ, New England Med Ctr, Dept Radiol, 750 Washington St,POB 299, Boston, MA 02111 USA. EM RMcCauley@tufts-nemc.org NR 8 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAY PY 2006 VL 36 IS 5 BP 449 EP 452 DI 10.1007/s00247-006-0122-5 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 030FK UT WOS:000236619500014 PM 16525768 ER PT J AU Jatana, M Singh, I Singh, AK Jenkins, D AF Jatana, M Singh, I Singh, AK Jenkins, D TI Combination of systemic hypothermia and N-acetylcysteine attenuates hypoxic-ischemic brain injury in neonatal rats SO PEDIATRIC RESEARCH LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; POSTISCHEMIC HYPOTHERMIA; MODERATE HYPOTHERMIA; PERINATAL ASPHYXIA; ENCEPHALOPATHY; DAMAGE; MODEL; NEUROPROTECTION; APOPTOSIS; PROTECTS AB Hypoxic ischemic (HI) injury in neonates may have devastating, long-term consequences. Recently completed clinical trials in HI neonates indicate that hypothermia within 6 h of birth results in modest improvement in the combined outcome of death or severe disability. The aim of this study was to investigate the effects of combining hypothermia and N-acetyleysteine (NAC) off brain injury, neonatal reflexes and myelination after neonatal HI. Seven-day-old rats were subjected to right common carotid artery ligation and hypoxia (8% oxygen) for 2 h. Systemic hypothermia (30 + 0.5 degrees C) was induced immediately after the period of HI and was maintained for 2 h. NAC (50 mg/kg) was administered by intraperitoneal injection daily until sacrifice. Brain infarct Volumes were significantly reduced at 48 h post-HI in the hypothermia plus NAC Group (21.5 +/- 3.84 mm(3)) compared with vehicle (240.85 +/- 4.08 mm(3)). Neonatal reflexes were also significantly improved by combination therapy at days 1 and 7. There was a significant loss of right hemispheric brain volume in the untreated group at 2 and 4 wk after HI insult. Brain volumes were preserved in hypothermia plus NAC group and were not significantly different when compared with the sham group. Similarly, increased myelin expression was seen in brain sections from hypothermia Plus NAC group, when stained for Luxol Fast Blue (LFB), Myelin Basic Protein (MBP) and Proteolipid protein (PLP). These results indicate that hypothermia plus NAC combination therapy improves infarct volume, myelin expression and functional outcomes after focal HI injury. C1 Med Univ S Carolina, Childrens Hosp, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Jenkins, D (reprint author), Med Univ S Carolina, Childrens Hosp, Dept Pediat, Room 662,POB 250917,165 Ashley Ave, Charleston, SC 29425 USA. EM eicherdj@musc.edu FU NINDS NIH HHS [NS-22576, NS-34741, NS-37766, NS-40144, NS-40810] NR 32 TC 61 Z9 61 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2006 VL 59 IS 5 BP 684 EP 689 DI 10.1203/01.pdr.0000215045.91122.44 PG 6 WC Pediatrics SC Pediatrics GA 035LX UT WOS:000237003800012 PM 16627882 ER PT J AU Dupin, MM Halliday, I Care, CM AF Dupin, MM Halliday, I Care, CM TI Simulation of a microfluidic flow-focusing device SO PHYSICAL REVIEW E LA English DT Article ID LATTICE BOLTZMANN-EQUATION; NAVIER-STOKES EQUATION; FLUIDS; MODEL AB We present a model of microfluidic flow of several completely immiscible fluids and use it to simulate a whole flow focusing device chamber. Our efficient, practical model supports a large parameter space, spanned by surface wetting, surface tension, liquid-liquid wetting, viscosity ratio, and inlet velocity. It is based upon an N-component lattice Boltzmann method with interrupted coalescence [Dupin , Philos. Trans. R. Soc. London, Ser. A 362, 1885 (2004)], here adapted for calculations at low capillary and Reynolds numbers, with wetting and significantly reduced spurious flow. Results over 2 orders of magnitude in Reynolds number are presented. C1 Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Sheffield Hallam Univ, Mat & Engn Res Inst, Sheffield S1 1WB, S Yorkshire, England. RP Dupin, MM (reprint author), Massachusetts Gen Hosp, Steele Lab, Boston, MA 02114 USA. OI Care, Christopher/0000-0003-2592-5280 NR 20 TC 45 Z9 46 U1 2 U2 17 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD MAY PY 2006 VL 73 IS 5 AR 055701 DI 10.1103/PhysRevE.73.055701 PN 2 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 048MO UT WOS:000237951400010 PM 16802991 ER PT J AU Randolph, MA Yaremchuk, MJ AF Randolph, MA Yaremchuk, MJ TI Clinical application of cultured autologous human auricular chondrocytes with autologous serum for craniofacial or nasal augmentation and repair SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID TISSUE-ENGINEERED CARTILAGE; ARTICULAR-CARTILAGE; POLYMER C1 Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. EM marandolph@partners.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2006 VL 117 IS 6 BP 2031 EP 2032 DI 10.1097/01.prs.0000210670.98945.5f PG 2 WC Surgery SC Surgery GA 046FV UT WOS:000237797700047 ER PT J AU Feng, JW Call, ME Wucherpfennig, KW AF Feng, Jianwen Call, Matthew E. Wucherpfennig, Kai W. TI The assembly of diverse immune receptors is focused on a polar membrane-embedded interaction site SO PLOS BIOLOGY LA English DT Article ID TRANSMEMBRANE ALPHA-HELICES; CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; T-CELLS; DRIVE ASSOCIATION; STRUCTURAL BASIS; FC-RECEPTOR; NK CELLS; COMPLEX; NKG2D AB The majority of receptors responsible for activation of distinct cell types within the immune system assemble with dimeric signaling modules through interaction of a basic transmembrane residue with a pair of acidic residues of the signaling dimer. Because assembly of other membrane proteins requires specific interactions along extended stretches of transmembrane helices, we examined how transmembrane sequences flanking the polar interaction site contribute to assembly for three receptors that associate with different signaling modules-the natural killer cell receptors KIR and NKG2D and the Fc receptor for IgA, Fc alpha RI. The KIR and NKG2D receptors assembled with the DAP12 and DAP10 dimers, respectively, even when the entire KIR or NKG2D transmembrane domains were replaced by polyleucine sequences with a properly positioned basic residue. In contrast, a high degree of specificity for the basic side chain could be observed because the KIR-DAP12 and Fc alpha RI-Fc gamma interactions favored lysine or arginine, respectively. Steric hindrance among incompatible extra-membranous domains and competition for signaling modules also contributed to specificity of assembly. These results demonstrate that these interactions are focused on the polar site created by three ionizable transmembrane residues, and explain how the DAP12 and Fc gamma signaling modules can assemble with large, non-overlapping sets of receptors that have highly divergent transmembrane sequences. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI054520] NR 42 TC 39 Z9 42 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAY PY 2006 VL 4 IS 5 BP 768 EP 779 AR e142 DI 10.1371/journal.pbio.0040142 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 048SN UT WOS:000237966900013 PM 16623599 ER PT J AU Beroukhim, R Lin, M Park, Y Hao, K Zhao, XJ Garraway, LA Fox, EA Hochberg, EP Mellinghoff, IK Hofer, MD Descazeaud, A Rubin, MA Meyerson, M Wong, WH Sellers, WR Li, C AF Beroukhim, Rameen Lin, Ming Park, Yuhyun Hao, Ke Zhao, Xiaojun Garraway, Levi A. Fox, Edward A. Hochberg, Ephraim P. Mellinghoff, Ingo K. Hofer, Matthias D. Descazeaud, Aurelien Rubin, Mark A. Meyerson, Matthew Wong, Wing Hung Sellers, William R. Li, Cheng TI Inferring loss-of-heterozygosity from unpaired tumors using high-density oligonucleotide SNP arrays SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; ALLELIC-LOSS; LUNG-CANCER; COPY NUMBER; GENOME; DNA; MICROARRAYS; DCHIPSNP; REGIONS; MODELS AB Loss of heterozygosity (LOH) of chromosomal regions bearing tumor suppressors is a key event in the evolution of epithelial and mesenchymal tumors. Identification of these regions usually relies on genotyping tumor and counterpart normal DNA and noting regions where heterozygous alleles in the normal DNA become homozygous in the tumor. However, paired normal samples for tumors and cell lines are often not available. With the advent of oligonucleotide arrays that simultaneously assay thousands of single- nucleotide polymorphism ( SNP) markers, genotyping can now be done at high enough resolution to allow identification of LOH events by the absence of heterozygous loci, without comparison to normal controls. Here we describe a hidden Markov model-based method to identify LOH from unpaired tumor samples, taking into account SNP intermarker distances, SNP-specific heterozygosity rates, and the haplotype structure of the human genome. When we applied the method to data genotyped on 100 K arrays, we correctly identified 99% of SNP markers as either retention or loss. We also correctly identified 81% of the regions of LOH, including 98% of regions greater than 3 megabases. By integrating copy number analysis into the method, we were able to distinguish LOH from allelic imbalance. Application of this method to data from a set of prostate samples without paired normals identified known regions of prevalent LOH. We have developed a method for analyzing high-density oligonucleotide SNP array data to accurately identify of regions of LOH and retention in tumors without the need for paired normal samples. C1 Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol & Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Pharmacol, Los Angeles, CA USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM william.sellers@novartis.com; cli@hsph.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Rubin, Mark/0000-0002-8321-9950; Descazeaud, Aurelien/0000-0002-2477-1550 FU NCI NIH HHS [T32 CA009172, R01CA109038, R01 CA109038, P20 CA096470, P20-CA96470]; NHGRI NIH HHS [1R01HG02341, R01 HG002341]; PHS HHS [P501062003] NR 30 TC 101 Z9 105 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2006 VL 2 IS 5 BP 323 EP 332 AR e41 DI 10.1371/journal.pcbi.0020041 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 070AY UT WOS:000239493900001 PM 16699594 ER PT J AU Strahilevitz, J Onodera, Y Hooper, DC AF Strahilevitz, J Onodera, Y Hooper, DC TI An improved expression plasmid for affinity purification of Staphylococcus aureus gyrase A subunit SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE expression plasmid; purification; solubility; thioredoxon; TEV; Staphylococcus aureus; gyrase ID TOPOISOMERASE-IV; DNA GYRASE; FUSION PROTEINS; THIOREDOXIN; FLUOROQUINOLONES; CIPROFLOXACIN; PROTEOLYSIS; QUINOLONES; RESISTANCE; STRAINS AB Of the bacterial topoisomerases, the gyrase A subunit (GyrA) of Staphylococcus aureus is particularly difficult to purify because of its tendency to form inclusion bodies. Previous attempts at purification yielded low concentrations of protein with reduced specific activity. To overcome this problem, we modified the commercially available plasmid expression vector, pBAD/Thio-TOPO, via the addition of DNA sequences encoding a hexahistidine tag upstream and a cleavage site for tobacco etch virus protease downstream of the gene encoding thioredoxin. The resulting expression system consisting of the modified plasmid, pSAGA7, and the recommended host strain, Escherichia coli TOP 10, facilitated high level expression of soluble GyrA and its affinity purification to over 95% homogeneity. Purified GyrA had high biological activity as evidenced by a specific activity of 4.3 x 10(5) U/mg. The pSAGA7/TOP10 expression system also facilitated the expression and purification of a subunit of S. aureus topoisomerase IV, ParE, and a recently discovered protein unrelated to topoisomerases, QnrB, two "hard to purify" proteins. We conclude that pSAGA7 might be useful for high-level soluble expression and purification of diverse microbial proteins. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, AI 23988] NR 20 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD MAY PY 2006 VL 47 IS 1 BP 10 EP 15 DI 10.1016/j.pep.2005.08.009 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 043MC UT WOS:000237604200002 PM 16289915 ER PT J AU Greene, RW Ablon, JS Martin, A AF Greene, RW Ablon, JS Martin, A TI Use of collaborative problem solving to reduce seclusion and restraint in child and adolescent inpatient units SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID SPECIAL SECTION; BEHAVIOR; YOUTHS AB The authors describe "collaborative problem solving," a cognitive-behavioral approach for working with aggressive children and adolescents. The model conceptualizes aggressive behavior as the byproduct of lagging cognitive skills in the domains of flexibility, frustration tolerance, and problem solving. The goal is to train staff to assess specific cognitive skills that may be contributing to challenging behavior and to teach children new skills through collaborative problem solving. The authors present results from an inpatient unit that dramatically reduced rates of seclusion and restraint. C1 Massachusetts Gen Hosp, Dept Psychiat, Collaborat Problem Solving Inst, Newton Corner, MA 02458 USA. Harvard Univ, Sch Med, Newton Corner, MA 02458 USA. Yale Univ, New Haven Childrens Hosp, Childrens Psychiat Impatient Serv, New Haven, CT 06520 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Greene, RW (reprint author), Collaborat Problem Solving Inst, 313 Washington St,Suite 402, Newton Corner, MA 02458 USA. EM greene@cpsinstitute.org NR 18 TC 38 Z9 38 U1 2 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2006 VL 57 IS 5 BP 610 EP 612 DI 10.1176/appi.ps.57.5.610 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 039JJ UT WOS:000237301500002 PM 16675751 ER PT J AU Tepper, MC AF Tepper, MC TI Symptoms of withdrawal: A memior of snapshots and redemption SO PSYCHIATRIC SERVICES LA English DT Book Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tepper, MC (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD MAY PY 2006 VL 57 IS 5 BP 744 EP 744 DI 10.1176/appi.ps.57.5.744 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 039JJ UT WOS:000237301500059 ER PT J AU Yehuda, R Yang, RK Buchsbaum, MS Golier, JA AF Yehuda, R Yang, RK Buchsbaum, MS Golier, JA TI Alterations in cortisol negative feedback inhibition as examined using the ACTH response to cortisol administration in PTSD SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PTSD; cortisol; ACTH; hypothalamic-pituitary-adrenal axis; negative feedback inhibition; glucocorticoid receptor ID POSTTRAUMATIC-STRESS-DISORDER; DEXAMETHASONE-SUPPRESSION; RAT-BRAIN; RECEPTOR; CORTICOSTERONE; PITUITARY AB Objective: Studies using the dexamethasone suppression test (DST) have demonstrated an enhanced negative feedback inhibition at the pituitary in PTSD, but have not provided information about central feedback effects, since dexamethasone (DEX) does not penetrate the brain well. The authors therefore examined the change in ACTH and cortisol before and after cortisol administration, which acts at central feedback sites in addition to peripheral targets. Method: Blood was obtained from 31 mate veterans (18 with PTSD) before, and 8, 40 and 95 min following injection of 17.5 mg cortisol and placebo. Results: A greater decline in ACTH was observed after cortisol injection in PTSD. Conclusions: Central as well as peripheral negative feedback inhibition may be altered in PTSD. Published by Elsevier Ltd. C1 Bronx Vet Affairs Med Ctr, Bronx VA OOMH, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, Bronx, NY USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@med.va.gov FU NCRR NIH HHS [5M01 RR 00071] NR 19 TC 51 Z9 52 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY PY 2006 VL 31 IS 4 BP 447 EP 451 DI 10.1016/j.psyneuen.2005.10.007 PG 5 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 029XJ UT WOS:000236597400004 PM 16364555 ER PT J AU Miller, MW Gronfier, C AF Miller, MW Gronfier, C TI Diurnal variation of the startle reflex in relation to HPA-axis activity in humans SO PSYCHOPHYSIOLOGY LA English DT Article DE startle; circadian rhythm; diurnal; cortisol ID CORTICOTROPIN-RELEASING FACTOR; POSTTRAUMATIC-STRESS-DISORDER; ACOUSTIC STARTLE; CIRCADIAN MODULATION; RATS; VETERANS; FEAR; CORTICOSTERONE; ANTAGONISTS; CIRCUIT AB Diurnal variation of baseline startle amplitude was examined in 14 normal inpatients on a research unit where behavioral activity and environmental stimuli were highly controlled. We tested a hypothesized association between diurnal variations of salivary cortisol and reflex amplitude by recording acoustic startle eyeblinks shortly before bedtime, when cortisol was near its lowest daily level, and just after awakening, when cortisol was at its peak. Results showed that startle eyeblinks were greater during evening than morning sessions, whereas the opposite was true for cortisol levels. Skin conductance levels and reaction time performance also increased from morning to evening. These findings are consistent with accumulating evidence suggesting a possible link between startle reactivity and hypothalamic-pituitary-adrenal axis activity, and an association between diurnal variations in endogenous arousal and startle amplitude. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Dept Psychiat, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Lyon 1, F-69365 Lyon, France. INSERM, U371, Dept Chronobiol, F-69500 Bron, France. Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 FU NCRR NIH HHS [M01 RR002635]; NIMH NIH HHS [MH45130, MH63959, R01 MH045130, R03 MH063959, R03 MH063959-01A1] NR 25 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD MAY PY 2006 VL 43 IS 3 BP 297 EP 301 DI 10.1111/j.1469-8986.2006.00400.x PG 5 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 060FJ UT WOS:000238787500009 PM 16805869 ER PT J AU Wittenberg, E Halpern, E Divi, N Prosser, LA Araki, SS Weeks, JC AF Wittenberg, E Halpern, E Divi, N Prosser, LA Araki, SS Weeks, JC TI The effect of age, race and gender on preference scores for hypothetical health states SO QUALITY OF LIFE RESEARCH LA English DT Article DE hypothetical health states; preferences; rater age; race; gender; utilities; values ID QUALITY-OF-LIFE; RACIAL-DIFFERENCES; PROSPECT-THEORY; PATIENT; CANCER; VALUES; VALUATION; EQ-5D; PERCEPTIONS; EXPERIENCE AB Purpose: Preferences are known to vary by individuals' personal experience with a health state, but variation among respondents' scoring of the same hypothetical state is unproven but relevant to the use of community-perspective preference scores. This research explored the systematic contribution of respondents' age, race and gender to variability in community perspective preferences for hypothetical health states. Methods: Data from four community samples were pooled for the analysis. Linear regression modeling was used to test for the effect of respondent age, race and gender on preference scores while controlling for health state severity. Results: In this sample of 956 preference scores from 390 individuals across 4 studies, older respondents provided lower preference scores for the same hypothetical health state compared with younger respondents (regression coefficient for 1 year of age = -0.002, p < 0.001), and white individuals provided higher preference scores for the same states compared with non-white individuals (regression coefficient = 0.056, p = 0.014). Conclusion: Preferences for hypothetical health states may vary by the age and race of the respondent providing the score. Community-perspective preferences should thus be elicited from large, random samples of the relevant population to ensure variation on these as well as other yet-unidentified characteristics that may affect scores. C1 MGH, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Stanford Univ, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. RP Wittenberg, E (reprint author), MGH, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM eve@mgh-ita.org NR 37 TC 9 Z9 9 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD MAY PY 2006 VL 15 IS 4 BP 645 EP 653 DI 10.1007/s11136-005-3514-3 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 041XE UT WOS:000237489100007 PM 16688497 ER PT J AU Kim, YH Blake, MA Harisinghani, MG Archer-Arroyo, K Hahn, PF Pitman, MB Mueller, PR AF Kim, Young H. Blake, Michael A. Harisinghani, Mukesh G. Archer-Arroyo, Krystal Hahn, Peter F. Pitman, Martha B. Mueller, Peter R. TI Adult intestinal intussusception: CT appearances and identification of a causative lead point SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 28-DEC 03, 2004 CL Chicago, IL SP Radiol Soc N Amer ID SMALL-BOWEL INTUSSUSCEPTION; GASTROINTESTINAL-TRACT; MECKEL DIVERTICULUM; MALFORMATIONS; LYMPHOMA; FEATURES; COLON AB The widespread application of computed tomography (CT) in different clinical situations has increased the detection of intussusception, particularly non-lead point intussusception, which tends to be transient. Consequently, determining the clinical significance of intussusception seen at CT poses a diagnostic challenge. Patients with intussusception may or may not be symptomatic, and symptoms can be acute, intermittent, or chronic, making clinical diagnosis difficult. In most cases, radiologists can readily make the correct diagnosis of intestinal intussusception by noting the typical bowel-within-bowel appearance at abdominal CT. However, the CT findings that help differentiate between lead point and non-lead point intussusception have not been well studied. Nevertheless, although there is considerable overlap of CT findings, when a lead mass is seen at CT as a separate and distinct entity vis-a-vis edematous bowel, it can be considered a reliable indicator of a lead point intussusception. Differentiating between lead point and non-lead point intussusception is important in determining the appropriate treatment and has the potential to reduce the prevalence of unnecessary surgery. (C) RSNA, 2006. C1 Univ Massachusetts, UMass Mem, Dept Radiol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, YH (reprint author), Univ Massachusetts, UMass Mem, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM kimy@ummhc.org OI Archer-Arroyo, Krystal/0000-0002-7844-9823 NR 26 TC 61 Z9 71 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2006 VL 26 IS 3 BP 733 EP U101 DI 10.1148/rg.263055100 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 064GZ UT WOS:000239078500009 PM 16702451 ER PT J AU Menezes, NM Olear, EA Li, X Connolly, SA Zurakowski, D Foley, M Shapiro, F Jaramillo, D AF Menezes, NM Olear, EA Li, X Connolly, SA Zurakowski, D Foley, M Shapiro, F Jaramillo, D TI Gadolinium-enhanced MR images of the growing piglet skeleton: Ionic versus nonionic contrast agent SO RADIOLOGY LA English DT Article ID DEVELOPING APPENDICULAR SKELETON; CALVE-PERTHES DISEASE; ARTICULAR-CARTILAGE; GROWTH-PLATE; GADOPENTETATE DIMEGLUMINE; VASCULAR CONTRIBUTION; OSTEOGENESIS; EPIPHYSEAL; CANALS; GLYCOSAMINOGLYCAN AB Purpose: To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Materials and Methods: Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Results: Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). Conclusion: The results suggest different roles for the two gadoliniumbased contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for evaluating cartilage fixed-charge density. C1 Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA 02129 USA. Huazhong Univ Sci & Technol, Wuhan 430074, Hubei, Peoples R China. Tongji Med Univ, Tongji Hosp, Dept Radiol, Wuhan, Hubei, Peoples R China. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Menezes, NM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. EM nmenezes@nmr.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR042396-09] NR 31 TC 16 Z9 18 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2006 VL 239 IS 2 BP 406 EP 414 DI 10.1148/radiol.2392050360 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 036QV UT WOS:000237090800013 PM 16641351 ER PT J AU Nicholas, PK Leuner, LD Hatfield, JM Corless, IB Marr, KH Mott, MK Cross-Skinner, S AF Nicholas, PK Leuner, LD Hatfield, JM Corless, IB Marr, KH Mott, MK Cross-Skinner, S TI Using the cancer rehabilitation questionnaire in patients with colorectal cancer SO REHABILITATION NURSING LA English DT Article DE cancer rehabilitation scale; colorectal cancer; instrument development nursing; quality of life; rehabilitation issues ID QUALITY-OF-LIFE; RESECTION AB This article describes the development and testing of the Cancer Rehabilitation Questionnaire (CRQ) in patients with colorectal cancer. A descriptive, correlational survey was conducted in a sample of patients with colon or rectal cancer who received care at an outpatient cancer clinic at a large, northeastern U.S. academic medical center. Patients were identified from the Tumor Registry (N = 327) and received a mailed questionnaire. One hundred and three patients with colorectal cancer completed the demographic questionnaire, the CRQ developed by the investigators, and the Quality of Life Index (QLI). Significant differences were found between individuals with colon cancer and individuals with rectal cancer on the total CRQ (p <.005) and the physical, future orientation, and role-relationship subscales. For the QLI, significantly lower scores were reported on the family subscale for patients with rectal cancer in comparison with those with colon cancer. More attention to rehabilitation issues and quality of life is required across the trajectory of the cancer experience. With the increasing incidence of colorectal cancer, nurses in rehabilitation practice must address the issues affecting patients with this disease as they progress from diagnosis to treatment and rehabilitation. C1 MGH Inst Hlth Profess, Grad Program Nursing, Boston, MA USA. Univ Cent Florida, Sch Nursing, Orlando, FL USA. Beverly Hosp, Beverly, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Phillips Andover Acad, Andover, MA USA. RP Nicholas, PK (reprint author), 36 1st Ave, Boston, MA 02129 USA. EM pnicholas@mghihp.edu NR 25 TC 5 Z9 5 U1 0 U2 2 PU ASSOCIATION REHABILITATION NURSES PI GLENVIEW PA 4700 W LAKE AVE, GLENVIEW, IL 60025-1485 USA SN 0278-4807 J9 REHABIL NURS JI Rehabil. Nurs. PD MAY-JUN PY 2006 VL 31 IS 3 BP 106 EP 113 PG 8 WC Nursing; Rehabilitation SC Nursing; Rehabilitation GA 040LS UT WOS:000237380700006 PM 16669572 ER PT J AU Caramez, MP Schettino, G Suchodolski, K Nishida, T Harris, RS Malhotra, A Kacmarek, RM AF Caramez, MP Schettino, G Suchodolski, K Nishida, T Harris, RS Malhotra, A Kacmarek, RM TI The impact of endotracheal suctioning on gas exchange and hemodynamics during lung-protective ventilation in acute respiratory distress syndrome SO RESPIRATORY CARE LA English DT Article DE airway suctioning; closed suctioning; open suctioning; lung-protective ventilation; intensive care; ventilator ID ARTERIAL OXYGEN DESATURATION; INJURY; CONSEQUENCES; PREVENTION; PRESSURES; VOLUME AB OBJECTIVE: To evaluate the respiratory and hemodynamic effects of open suctioning (OS) versus closed suctioning (CS) during pressure-control (PC) and volume-control (VC) ventilation, using a lung-protective ventilation strategy in an animal model of acute respiratory distress syndrome (ARDS). SETTING: Animal laboratory in a university hospital. DESIGN: Randomized cross-over evaluation. ANIMALS: Eight female Dorset sheep. INTERVENTIONS: Lung lavage was used to simulate ARDS. We applied VC and PC mechanical ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure (PEEP), adjusted based on a table of PEEP versus fraction of inspired oxygen (FIO2). Suctioning was performed for 10 s with a suction pressure of -100 mm Hg, during both OS and CS. OS and CS were randomly performed with each animal. Hemodynamics and arterial blood gases were recorded before, during, and after endotracheal suctioning. RESULTS: The P-aO2/F-IO2 ratios before suctioning were similar in all groups, as were the PEEP and F-IO2. P-aO2/F-IO2 was lower after OS than after CS/VC or CS/PC. There was no post-suctioning difference in oxygenation between CS/VC and CS/PC. P-aCO2 recorded 10 min after suctioning was greater than the presuctioning value, in all groups. Intrapulmonary shunt fraction increased between baseline and 10 min post-suctioning with OS and CS/VC, but did not significantly increase with CS/PC. There were no significant changes in hemodynamics pre-suctioning versus post-suctioning with OS, CS/VC, or CS/PC. CONCLUSION: P-aO2/F-IO2 was better maintained during CS with both VC and PC modes during lung-protective ventilation for ARDS, as compared with OS, and shunt fraction post-suctioning changed least with PC. C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pulm & Crit Care Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org FU NHLBI NIH HHS [R01 HL073146, R01 HL073146-01]; NIA NIH HHS [K23 AG024837-02, K23 AG024837] NR 22 TC 9 Z9 11 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESPIR CARE JI Respir. Care PD MAY PY 2006 VL 51 IS 5 BP 497 EP 502 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 040SU UT WOS:000237401500003 PM 16638159 ER PT J AU Yu, SY Damico, FM Viola, F D'Amico, DJ Young, LH AF Yu, Seung-Young Damico, Francisco Max Viola, Francesco D'Amico, Donald J. Young, Lucy H. TI Retinal toxicity of intravitreal triamcinolone acetonide SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT Annual Meeting of the Retina-Society CY SEP 30-OCT 03, 2004 CL Baltimore, MD SP Retina Soc ID CYSTOID MACULAR EDEMA; RANDOMIZED CLINICAL-TRIAL; PROLIFERATIVE VITREORETINOPATHY; NONINFECTIOUS ENDOPHTHALMITIS; VEIN OCCLUSION; INJECTION; NEOVASCULARIZATION; DEGENERATION; EYES AB Purpose: To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. Methods: Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. Results: No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. Conclusion: Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Young, LH (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles st, Boston, MA 02114 USA. EM lhyoung@meei.harvard.edu NR 32 TC 45 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD MAY-JUN PY 2006 VL 26 IS 5 BP 531 EP 536 DI 10.1097/00006982-200605000-00006 PG 6 WC Ophthalmology SC Ophthalmology GA 100QZ UT WOS:000241685000006 PM 16770259 ER PT J AU Mount, DB Kwon, CY Zandi-Nejad, K AF Mount, DB Kwon, CY Zandi-Nejad, K TI Renal urate transport SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID URIC-ACID NEPHROLITHIASIS; BRUSH-BORDER MEMBRANE; PARA-AMINOHIPPURATE TRANSPORT; XANTHINE OXIDOREDUCTASE GENE; NICOTINIC-ACID; INSULIN-RESISTANCE; ANION-EXCHANGER; EVOLUTIONARY IMPLICATIONS; MOLECULAR-IDENTIFICATION; CARDIOVASCULAR-DISEASE AB Serum uric acid is determined by a balance between production and renal excretion. Luminal reabsorption of urate by the proximal tubule from the glomerular ultrafiltrate involves coupling between sodium-anion cotransport and urate-anion exchange. Apical sodium-coupled cotransport of lactate, ketoacids, nicotinate, and pyrazinoate increases intracellular levels of these anions in proximal tubular cells, stimulating the apical absorption of luminal urate via anion exchange. Hyperuricemia occurs when plasma levels of these anions increase; for example, hyperuricemia is a well-recognized concomitant of lactic acidosis and ketoacidosis. Relevant developments in the molecular and renal physiology of urate homeostasis are reviewed. C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. VA Boston Healthcare Syst, Div Gen Internal Med, Boston, MA USA. Childrens Hosp, Div Renal, Boston, MA 02115 USA. RP Mount, DB (reprint author), Brigham & Womens Hosp, Div Renal, Room 540,HIM Bldg,4 Blackfan Circle, Boston, MA 02115 USA. EM dmount@rics.bwh.harvard.edu FU NIDDK NIH HHS [R01 DK-57708] NR 153 TC 43 Z9 50 U1 1 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 2006 VL 32 IS 2 BP 313 EP + DI 10.1016/j.rdc.2006.02.006 PG 20 WC Rheumatology SC Rheumatology GA 053VC UT WOS:000238332800006 PM 16716882 ER PT J AU Dai, L Pessler, F Chen, LX Clayburne, G Schumacher, HR AF Dai, L Pessler, F Chen, LX Clayburne, G Schumacher, HR TI Detection and initial characterization of synovial lining fragments in synovial fluid SO RHEUMATOLOGY LA English DT Article DE CD68; rice bodies; synovial lining; synovial fluid; synovial fluid analysis; synovium ID RHEUMATOID-ARTHRITIS; RICE BODIES; FIBROBLASTS; KNEE; LAVAGE AB Objective. Free fragments of synovium have occasionally been seen in synovial fluid but have not been studied systematically. We wished to establish a method for the reliable detection of these fragments in joint and bursa effusions and begin to characterize them by histochemical and immunohistochemical methods. Methods. Cell smears, wet drop preparations and cytospins were prepared from 39 consecutive joint and bursa effusions. Paraffin cell blocks were prepared from a subset. Analysis encompassed standard and polarized light microscopy, histochemistry, immunohistochemistry and transmission electron microscopy (EM). Synovial biopsy tissue from one different patient was examined for comparison. Results. Tissue fragments were not seen in Wright-stained cell smears and only rarely in wet drop preparations. In contrast, variously sized fragments with the histological appearance of hyperplastic synovial lining were detected in ethanol-fixed, haematoxylin/eosin-stained cytospins from bursitis and all arthropathies studied [17/24 (71%) of non-inflammatory and 12/15 (80%) of inflammatory specimens]. Immunostaining revealed CD68 expression in a subset of cells in a pattern characteristic of hyperplastic synovial lining. Juxtaposed cells with morphological features of macrophage-like and fibroblast-like synoviocytes were seen by EM. Conclusions. Synovial lining fragments can be detected in effusions from diverse arthropathies and bursitis. They maintain important properties of the synovial lining and can be analysed by immunohistochemistry. They may afford the opportunity to study a relatively pure preparation of synovial lining cells without the need for cell culture, and to evaluate their possible role in augmenting or perpetuating synovitis or joint damage. C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Presbyterian Med Ctr, Philadelphia, PA USA. Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou, Peoples R China. RP Dai, L (reprint author), Univ Penn, Philadelphia, PA 19104 USA. EM liedai2004@hotmail.com; schumacr@mail.med.upenn.edu FU NCI NIH HHS [T32-CA09140]; NIAMS NIH HHS [T32-AR007442] NR 16 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD MAY PY 2006 VL 45 IS 5 BP 533 EP 537 DI 10.1093/rheumatology/kei206 PG 5 WC Rheumatology SC Rheumatology GA 035KA UT WOS:000236998500007 PM 16352640 ER PT J AU Bloch, DB Gulick, T Bloch, KD Yang, WH AF Bloch, DB Gulick, T Bloch, KD Yang, WH TI Processing body autoantibodies reconsidered SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE mRNA processing body; mRNA decay; RISC complex; autoantigen ID GW BODIES; GW182; DECAY AB Processing bodies (P-bodies) are cellular structures that have critical roles in mRNA degradation and post-transcriptional gene silencing. Some patients with autoimmune disease have high titer antibodies directed against P-bodies, and certain sera have been used as markers for the GW182 component of these structures. This study shows that available reference sera are unreliable markers for GW182 because the sera contain antibodies directed against Ge-1, a second P-body autoantigen. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02114 USA. Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp, Dept Med, CNY 8302,149 13th St, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu NR 10 TC 14 Z9 16 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 2006 VL 12 IS 5 BP 707 EP 709 DI 10.1261/rna.17406 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038QI UT WOS:000237237500002 PM 16641511 ER PT J AU Yen, LS Magnier, M Weissleder, R Stockwell, BR Mulligan, RC AF Yen, LS Magnier, M Weissleder, R Stockwell, BR Mulligan, RC TI Identification of inhibitors of ribozyme self-cleavage in mammalian cells via high-throughput screening of chemical libraries SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE gene regulation; ribozyme; self-cleavage; ribozyme inhibitors; toyocamycin; 5-fluorouridine ID HAMMERHEAD-RIBOZYME; GENE-EXPRESSION; BIOCHEMICAL PROPERTIES; RNA; TUBERCIDIN; MECHANISM; SYSTEM; SCHISTOSOMIASIS; 5-FLUOROURACIL; TOYOCAMYCIN AB We have recently described an RNA-only gene regulation system for mammalian cells in which inhibition of self-cleavage of an mRNA carrying ribozyme sequences provides the basis for control of gene expression. An important proof of principle for that system was provided by demonstrating the ability of one specific small molecule inhibitor of RNA self-cleavage, toyocamycin, to control gene expression in vitro and vivo. Here, we describe the development of the high-throughput screening (HTS) assay that led to the identification of toyocamycin and other molecules capable of inhibiting RNA self-cleavage in mammalian cells. To identify small molecules that can serve as inhibitors of ribozyme self-cleavage, we established a cell-based assay in which expression of a luciferase (luc) reporter is controlled by ribozyme sequences, and screened 58,076 compounds for their ability to induce luciferase expression. Fifteen compounds able to inhibit ribozyme self-cleavage in cells were identified through this screen. The most potent of the inhibitors identified were toyocamycin and 5-fluorouridine (FUR), nucleoside analogs carrying modifications of the 7-position and 5-position of the purine or pyrimidine bases. Individually, these two compounds were able to induce gene expression of the ribozyme-controlled reporter; 365-fold and 110-fold, respectively. Studies of the mechanism of action of the ribozyme inhibitors indicate that the compounds must be incorporated into RNA in order to inhibit RNA self-cleavage. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Mol Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Columbia Univ, Fairchild Ctr, Dept Biol Sci, New York, NY 10027 USA. Columbia Univ, Fairchild Ctr, Dept Chem, New York, NY 10027 USA. RP Mulligan, RC (reprint author), Harvard Univ, Inst Med, Harvard Gene Therapy Initiat, Suite 407,4 Blackfan Circle, Boston, MA 02115 USA. EM mulligan@receptor.med.harvard.edu FU NCI NIH HHS [R01 CA097061, R24 CA092782, 1R01CA097061] NR 35 TC 39 Z9 41 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAY PY 2006 VL 12 IS 5 BP 797 EP 806 DI 10.1261/rna.2300406 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 038QI UT WOS:000237237500011 PM 16556935 ER PT J AU Zhong, Z Ksiezak-Reding, H Riggio, S Haroutunian, V Pasinetti, GM AF Zhong, Z Ksiezak-Reding, H Riggio, S Haroutunian, V Pasinetti, GM TI Insulin receptor deficits in schizophrenia and in cellular and animal models of insulin receptor dysfunction SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; prefrontal cortex; insulin resistance; insulin receptor; Akt; glycogen synthase kinase 3 alpha; glycogen synthase kinase 3 beta ID GLYCOGEN-SYNTHASE KINASE-3; ATYPICAL ANTIPSYCHOTIC-DRUGS; LONG-TERM POTENTIATION; PHOSPHATIDYLINOSITOL 3-KINASE; PSYCHIATRIC-PATIENTS; GLUCOSE-HOMEOSTASIS; DIABETES-MELLITUS; GENE-EXPRESSION; FRONTAL-CORTEX; PC12 CELLS AB Schizophrenia is associated with abnormalities in glucose metabolism that may lead to insulin resistance and a 3 fold higher incidence of type H diabetes mellitus. The goal of the present studies was to assess the role of insulin-dependent Akt signaling in schizophrenia and in animal and cellular models of insulin resistance. Our studies revealed a functional decrease in insulin receptor (IR)-mediated signal transduction in the dorsolateral prefrontal cortex (BA46) of medicated schizophrenics relative to control patients using post-mortem brain material. We found similar to 50% decreases in the content and autophosphorylation levels of IR beta and similar to 76-78% decreases in Akt content and activity (pSer(473)-Akt). The inhibition of IR beta signaling was accompanied by an elevated content of glycogen synthase kinase (GSK)-3 alpha and GSK-3 beta without significant changes in phospho-Ser(21/9) GSK-3 alpha/beta levels. A cellular model of insulin resistance was induced by IR beta knockdown (siRNA). As in schizophrenia, the IR beta knockdown cells demonstrated a reduction in the Akt content and activity. Total GSK-3 alpha/beta content remained unaltered, but phospho-Ser(21/9) GSK-3 alpha/beta levels were reduced indicating a net increase in the overall enzyme activity similar to that in schizophrenia. Insulin resistance phenotype was induced in mice by treatment with antipsychotic drug, clozapine. Behavioral testing showed decreases in startle response magnitude in animals treated with clozapine for 68 days. The treatment resulted in a functional inhibition of IR beta but the Akt activation status remained unaltered. Changes in GSK-3 alpha/beta were consistent with a net decrease in the enzyme activity, as opposed to that in schizophrenia. The results suggest that alterations in insulin-dependent Akt signaling in schizophrenia are similar to those observed in our cellular but not animal models of insulin resistance. In animal model, clozapine ameliorates IR beta deficits at the GSK-3 alpha/beta level, which may justify its role in treatment of schizophrenia. Our studies suggest that aberrant IR function may be important in the pathophysiology of schizophrenia. (c) 2006 Elsevier B.V. All rights reserved. C1 Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. Mt Sinai Sch Med, Neuroinflammat Res Labs, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA. RP Ksiezak-Reding, H (reprint author), Bronx Vet Adm Med Ctr, Dept Psychiat, Rm 3F-24,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM hanna.reding@mssm.edu NR 66 TC 1 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY PY 2006 VL 84 IS 1 BP 1 EP 14 DI 10.1016/j.schres.2006.02.009 PG 14 WC Psychiatry SC Psychiatry GA 051KP UT WOS:000238160300001 ER PT J AU Rosner, A Schmidt, EV Shyamala, G Maglione, JE Manner, CK Perkins, AS Gregg, JP Cardiff, RD AF Rosner, A. Schmidt, E. V. Shyamala, G. Maglione, J. E. Manner, C. K. Perkins, A. S. Gregg, J. P. Cardiff, R. D. TI Genotype-phenotype correlation in mouse models of human breast cancer SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 12th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY MAY 25-28, 2006 CL Dresden, GERMANY SP Deutsch Gesell Radioonkol C1 Tech Univ Dresden, Klin & Poliklin Strahlentherapie & Radioonkol, Med Fak Carl Gustav Carus, D-8027 Dresden, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hosp Canc Ctr, Cambridge, MA 02138 USA. Univ Calif Berkeley, Div Life Sci, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Univ Calif San Diego, Sch Med, Ctr Canc, Dept Med, La Jolla, CA 92093 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. Univ Calif Davis, Sch Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2006 VL 182 SU 1 BP 92 EP 92 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 050ZB UT WOS:000238128700281 ER PT J AU Parodi, K Paganetti, H Shih, HA Bonab, AA Cascio, EW Michaud, S Loeffler, JS DeLaney, TF Liebsch, N Munzenrider, JE Flanz, JB Lohmann, K Alpert, NM Fischman, AJ Bortfeld, T AF Parodi, K. Paganetti, H. Shih, H. A. Bonab, A. A. Cascio, E. W. Michaud, S. Loeffler, J. S. DeLaney, T. F. Liebsch, N. Munzenrider, J. E. Flanz, J. B. Lohmann, K. Alpert, N. M. Fischman, A. J. Bortfeld, T. TI PET/CT image guidance for treatment verification after proton therapy: An experimental study SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 12th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY MAY 25-28, 2006 CL Dresden, GERMANY SP Deutsch Gesell Radioonkol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. CPS Innovat, Knoxville, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2006 VL 182 SU 1 BP 137 EP 137 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 050ZB UT WOS:000238128700416 ER PT J AU Rietzel, E Chen, GTY AF Rietzel, E. Chen, G. T. Y. TI 4D radiotherapy: imaging and treatment planning SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Meeting Abstract CT 12th Congress of the Deutschen-Gesellschaft-fur-Radioonkologie CY MAY 25-28, 2006 CL Dresden, GERMANY SP Deutsch Gesell Radioonkol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2006 VL 182 SU 1 BP 137 EP 138 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 050ZB UT WOS:000238128700417 ER PT J AU Rattner, D Hawes, RH AF Rattner, D Hawes, RH TI NOTES: Gathering momentum SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Rattner, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 9 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAY PY 2006 VL 20 IS 5 BP 711 EP 712 DI 10.1007/s00464-006-0263-5 PG 2 WC Surgery SC Surgery GA 057RZ UT WOS:000238614200001 PM 16680515 ER PT J AU Peretti, GM Xu, JW Bonassar, LJ Kirchhoff, CH Yaremchuk, MJ Randolph, MA AF Peretti, GM Xu, JW Bonassar, LJ Kirchhoff, CH Yaremchuk, MJ Randolph, MA TI Review of injectable cartilage engineering using fibrin gel in mice and swine models SO TISSUE ENGINEERING LA English DT Review ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; FRESH OSTEOCHONDRAL ALLOGRAFTS; IN-SITU PHOTOPOLYMERIZATION; RABBIT-ARTICULAR-CARTILAGE; FULL-THICKNESS DEFECTS; ALGINATE BEADS; TRANSDERMAL PHOTOPOLYMERIZATION; BIOMECHANICAL ANALYSIS; CULTURED CHONDROCYTES; EXTRACELLULAR-MATRIX AB More than a decade of work has been devoted to engineering cartilage for articular surface repair. This review covers the use of fibrin gel polymer as an injectable scaffold for generating new cartilage matrix from isolated articular chondrocytes beginning with studies in mice and culminating in an applied study in swine joints. These studies began with developing a formulation of fibrin that was injectable and promoted cartilage matrix formation. Subsequent studies addressed the problems of volume loss after the scaffolds were placed in vivo by adding lyophilized cartilage matrix. Additional studies focused on the ability of isolated chondrocytes to heal and repair cartilage in a model that could be biomechanically tested. In conclusion, this series of studies demonstrated that fibrin gel is a suitable polymer gel for generating new cartilage matrix from articular chondrocytes. The new matrix is capable of forming mechanical bonds between cartilage disks and can lead to healing and integration. Armed with these results, implantation of fibrin-cell constructs into defects in swine knees showed new cartilage formation and filling of the defects. Continuing work in these models with fibrin and other polymerizable hydrogels could result in a suitable cell-based therapy for articular cartilage lesions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Plast Surg Res Lab, Boston, MA 02114 USA. Univ Vita Salute, Hosp San Raffaele, Milan, Italy. Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. Cornell Univ, Dept Biomed Engn, Ithaca, NY USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Plast Surg Res Lab, WACC 453,15 Parkman St, Boston, MA 02114 USA. EM marandolph@partners.org RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 80 TC 91 Z9 93 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAY PY 2006 VL 12 IS 5 BP 1151 EP 1168 DI 10.1089/ten.2006.12.1151 PG 18 WC Cell & Tissue Engineering SC Cell Biology GA 057FB UT WOS:000238580600003 PM 16771631 ER PT J AU Sun, W Yan, YN Lin, F Spector, M AF Sun, W Yan, YN Lin, F Spector, M TI Biomanufacturing: A US-China National Science Foundation-sponsored workshop SO TISSUE ENGINEERING LA English DT Article ID TISSUE ENGINEERING SCAFFOLDS; IN-VITRO; COMPOSITE; DEPOSITION; DESIGN; ARCHITECTURE; FABRICATION; CONSTRUCTS; POROSITY; CELLS AB A recent US-China National Science Foundation-sponsored workshop on biomanufacturing reviewed the state-of-the-art of an array of new technologies for producing scaffolds for tissue engineering, providing precision multi-scale control of material, architecture, and cells. One broad category of such techniques has been termed solid freeform fabrication. The techniques in this category include: stereolithography, selected laser sintering, single- and multiple-nozzle deposition and fused deposition modeling, and three-dimensional printing. The precise and repetitive placement of material and cells in a three-dimensional construct at the micrometer length scale demands computer control. These novel computer-controlled scaffold production techniques, when coupled with computer-based imaging and structural modeling methods for the production of the templates for the scaffolds, define an emerging field of computer-aided tissue engineering. In formulating the questions that remain to be answered and discussing the knowledge required to further advance the field, the Workshop provided a basis for recommendations for future work. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Drexel Univ, Philadelphia, PA 19104 USA. Tsing Hua Univ, Dept Engn Mech, Beijing 100084, Peoples R China. RP Spector, M (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Mail Stop 151,150 S Huntington Ave, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu RI Lin, Feng/K-7906-2012 OI Lin, Feng/0000-0003-1855-504X NR 31 TC 12 Z9 15 U1 0 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAY PY 2006 VL 12 IS 5 BP 1169 EP 1181 DI 10.1089/ten.2006.12.1169 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 057FB UT WOS:000238580600004 PM 16771632 ER PT J AU Shinoda, M Tilles, AW Wakabayashi, G Takayanagi, A Harada, H Obara, H Suganuma, K Berthiaume, F Shimazu, M Shimizu, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML AF Shinoda, M Tilles, AW Wakabayashi, G Takayanagi, A Harada, H Obara, H Suganuma, K Berthiaume, F Shimazu, M Shimizu, N Kitajima, M Tompkins, RG Toner, M Yarmush, ML TI Treatment of fulminant hepatic failure in rats using a bioartificial liver device containing porcine hepatocytes producing interleukin-1 receptor antagonist SO TISSUE ENGINEERING LA English DT Article ID TUMOR-NECROSIS-FACTOR; PIG ENDOGENOUS RETROVIRUS; SANDWICH CONFIGURATION; ISCHEMIA-REPERFUSION; IN-VITRO; EXPRESSION; INFECTION; PROTEIN; CELLS; GENE AB Fulminant hepatic failure (FHF) is a serious clinical condition that is associated with high mortality. There is evidence that FHF is an inflammatory disease, which is supported clinically by elevated serum levels of cytokines. In an effort to develop hepatocytes with additional functions for use in our bioartificial liver (BAL) device, we focused on interleukin-1 (IL-1) blockade as a therapeutic modality. Primary porcine hepatocytes were isolated from the livers of miniature swine and then transfected with an adenoviral vector encoding human interleukin-1 receptor antagonist (AdIL-1Ra). The transfected hepatocytes secreted human IL-1Ra. These transfected hepatocytes were incorporated into a flat-plate BAL device to evaluate their efficacy in treating D-galactosamine (GalN)-induced FHF in a rat model. After extracorporeal perfusion with the BAL device containing the transfected hepatocytes, there were significant reductions in the plasma levels of hepatic enzymes (aspartate aminotransferase and alanine aminotransferase) and cytokines (IL-1 and IL-6), indicating a beneficial effect. Animal survival was significantly improved in the treated group compared to the control group. These experiments demonstrate that combining inflammatory cytokine blockade with a functional BAL device may be an effective therapeutic option in the treatment of FHF. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Keio Univ, Sch Med, Dept Surg, Tokyo 1608582, Japan. Keio Univ, Sch Med, Dept Mol Biol, Tokyo 1608582, Japan. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, 51 Blossom Str, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK043371, DK43371, P30 DK040561-11, P30 DK040561] NR 34 TC 13 Z9 18 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD MAY PY 2006 VL 12 IS 5 BP 1313 EP 1323 DI 10.1089/ten.2006.12.1313 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 057FB UT WOS:000238580600016 PM 16771644 ER PT J AU Vickers, SM Squitieri, LS Spector, M AF Vickers, Scott M. Squitieri, Lee S. Spector, Myron TI Effects of cross-linking type II collagen-GAG scaffolds on chondrogenesis in vitro: Dynamic pore reduction promotes cartilage formation SO TISSUE ENGINEERING LA English DT Article ID TISSUE ENGINEERED CARTILAGE; GLYCOSAMINOGLYCAN SCAFFOLDS; ARTICULAR CHONDROCYTES; SEEDING DENSITY; OXYGEN-TENSION; MATRIX; CONTRACTION; CONDENSATION; BIOREACTOR; CULTURE AB Articular cartilage tissue-engineering investigations often implement bioassays for chondrogenesis in vitro using articular chondrocytes or mesenchymal stem cells in cell pellets that contract with time in culture, suggesting an association between the processes of contraction of the cell pellet and cartilage formation. The objective of the present study was to investigate this relationship further using adult canine articular chondrocyte-seeded type II collagen-GAG scaffolds. The collagen-GAG scaffolds were chemically cross-linked to achieve a range of cross-link densities. Chondrocyte-seeded scaffolds of varying cross-link densities were then cultured for 2 weeks to evaluate the effect of cross-link density on scaffold contraction and chondrogenesis. Scaffolds with low cross-link densities experienced cell-mediated contraction, increased cell number densities, a greater degree of chondrogenesis (viz., chondrocytic morphology of cells, synthesis of type II collagen), and an apparent increase in the rate of degradation of the scaffold compared to more highly cross-linked scaffolds that resisted cellular contraction. The results of this study suggest the promise of "dynamic pore reduction" for scaffolds for articular cartilage tissue engineering. In this approach, scaffolds would have an initial pore diameter large enough to facilitate cell seeding and a mechanical stiffness low enough to allow for cell-mediated contraction to yield a reduced pore volume to favor chondrogenesis. This approach may provide a useful alternative to traditional means of increasing cell number density and retention of synthesized molecules that promote cartilage formation in tissue-engineered constructs. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, Boston Campus,Room D1-152,Mail Stop 151 Res,150 S, Boston, MA 02130 USA. EM mspector@rics.bwh.harvard.edu NR 29 TC 84 Z9 84 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2152-4947 J9 TISSUE ENG JI Tissue Eng. PD MAY PY 2006 VL 12 IS 5 BP 1345 EP 1355 DI 10.1089/ten.2006.12.1345 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 057FB UT WOS:000238580600019 PM 16771647 ER PT J AU Darabi, K Abdel-Wahab, O Dzik, WH AF Darabi, K Abdel-Wahab, O Dzik, WH TI Current usage of intravenous immune globulin and the rationale behind it: the Massachusetts General Hospital data and a review of the literature SO TRANSFUSION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIFOCAL MOTOR NEUROPATHY; AUTOIMMUNE HEMOLYTIC-ANEMIA; IMMUNODEFICIENCY-VIRUS INFECTION; BONE-MARROW TRANSPLANTATION; PLACEBO-CONTROLLED TRIAL; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; A STREPTOCOCCAL INFECTIONS; GUILLAIN-BARRE-SYNDROME; BIRTH-WEIGHT INFANTS AB BACKGROUND: Intravenous immune globulin (IVIG) has been approved by the Food and Drug Administration (FDA) for use in 6 conditions: immune thrombocytopenic purpura (ITP), primary immunodeficiency, secondary immunodeficiency, pediatric HIV infection, Kawasaki disease, prevention of graft versus host disease (GVHD) and infection in bone marrow transplant recipients. However, most usage is for off-label indications, and for some of these comprehensive guidelines have been published. STUDY DESIGN AND METHODS: We retrospectively reviewed all approved IVIG transfusions at Massachusetts General Hospital in 2004 to identify the current usage pattern and completed a literature review. RESULTS: IVIG was most commonly used in the treatment of chronic neuropathy, which included chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy. For such patients, the annual cost of IVIG can exceed $50,000 per patient. Other common indications were the treatment of hypogammaglobulinemia, ITP, renal transplant rejection, myasthenia gravis, Guillain-Barre syndrome, necrotizing fasciitis, autoimmune hemolytic anemia, and Kawasaki disease. IVIG was administered in a variety of other indications each representing < 3% of the total treated patients. CONCLUSION: Only a few indications account for most of the usage for IVIG. Reports concerning IVIG continue to grow at a tremendous pace but few high-quality randomized controlled trials have been reported. Randomized trials are especially needed for conditions such as CIDP, which consume large quantities of product. C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Joint Program Transfus Med, Boston, MA 02115 USA. RP Darabi, K (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, GRJ 148,55 Fruit St, Boston, MA 02114 USA. EM kamrandarabi@yahoo.com NR 94 TC 84 Z9 87 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2006 VL 46 IS 5 BP 741 EP 753 DI 10.1111/j.1537-2995.2006.00792.x PG 13 WC Hematology SC Hematology GA 036TK UT WOS:000237098200010 PM 16686841 ER PT J AU Mora, JR von Andrian, UH AF Mora, JR von Andrian, UH TI T-cell homing specificity and plasticity: new concepts and future challenges SO TRENDS IN IMMUNOLOGY LA English DT Review ID LYMPHOCYTE-ASSOCIATED ANTIGEN; MUCOSAL VASCULAR ADDRESSIN; THYMUS-EXPRESSED CHEMOKINE; SELECTIN LIGAND FORMATION; PATCH DENDRITIC CELLS; IN-VIVO; CUTTING EDGE; MEMORY CELLS; P-SELECTIN; PERIPHERAL-TISSUES AB Naive and effector/memory T cells have distinct repertoires of trafficking ligands and receptors that restrict their ability to interact with specialized microvessels in different anatomical compartments and, consequently, have distinct patterns of migration. Antigen-experienced lymphocytes can be further subdivided into different subsets based on their expression of characteristic sets of trafficking receptors that favor their accumulation in certain target organs, including the skin and gut. Here, we summarize recent advances that have broadened our understanding of the cellular and molecular events that induce the generation of tissue-specific effector/memory T cells and discuss how these mechanisms could be harnessed for the therapeutic manipulation of T-cell-dependent pathologies. C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL 62524, HL 54936, P01 HL056949]; NIAID NIH HHS [AI 061663] NR 77 TC 180 Z9 185 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2006 VL 27 IS 5 BP 235 EP 243 DI 10.1016/j.it.2006.03.007 PG 9 WC Immunology SC Immunology GA 047XV UT WOS:000237912900007 PM 16580261 ER PT J AU Sherwood, RI Wagers, AJ AF Sherwood, Richard I. Wagers, Amy J. TI Harnessing the potential of myogenic satellite cells SO TRENDS IN MOLECULAR MEDICINE LA English DT Article ID MUSCLE PROGENITOR CELLS; SKELETAL-MUSCLE; SELF-RENEWAL; STEM-CELLS; REGENERATION; POPULATION; SPECIFICATION; HETEROGENEITY; ORIGIN; MOUSE AB Adult skeletal muscle has remarkable regenerative potential, which is mainly attributable to a small population of undifferentiated skeletal muscle precursors called satellite cells. These cells reside underneath the basal lamina of skeletal myofibers and can be activated to proliferate, differentiate and fuse to form new muscle tissue. Satellite cells have long been considered promising mediators of therapeutic muscle regeneration. However, in practice, the regenerative function of such cells, which in many cases have been derived or expanded by ex vivo cultures, can be surprisingly low. A recent study from Montarras and colleagues has provided new insights into the requirements for efficient muscle engraftment from purified muscle satellite cells, suggesting possible strategies to enhance their therapeutic potential. C1 Harvard Univ, Sch Med, Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Wagers, AJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Joslin Diabet Ctr,Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. EM amy.wagers@joslin.harvard.edu NR 22 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD MAY PY 2006 VL 12 IS 5 BP 189 EP 192 DI 10.1016/j.molmed.2006.03.002 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 060TX UT WOS:000238825600002 PM 16595190 ER PT J AU Garzotto, M Myrthue, A Higano, CS Beer, TM AF Garzotto, M Myrthue, A Higano, CS Beer, TM TI Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Urologic-Oncology CY MAY, 2005 CL San Antonio, TX SP Soc Urol Oncol DE chemotherapy; neoadjuvant; advanced prostate cancer; docetaxel; mitoxantrone ID RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; RADIATION-THERAPY; HORMONAL-THERAPY; PROGNOSTIC VARIABLES; DISEASE RECURRENCE; PLUS PREDNISONE; RADIOTHERAPY; CHEMOTHERAPY AB Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m(2)), with increasing doses of mitoxantrone (2-5 mg/m(2)) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. Results: The maximally tolerated dose for mitoxantrone was 4 mg/m(2), and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients. Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity. Published by Elsevier Inc. C1 Portland VA Med Ctr, Urol Sect, Surg Serv, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Urol & Renal Transplantat, Portland, OR 97239 USA. Univ Washington, Div Urol, Seattle, WA 98109 USA. Univ Washington, Div Oncol, Seattle, WA 98109 USA. RP Garzotto, M (reprint author), Portland VA Med Ctr, Urol Sect, Surg Serv, Portland, OR 97239 USA. EM garzotto@ohsu.edu NR 31 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2006 VL 24 IS 3 BP 254 EP 259 DI 10.1016/j.urolonc.2005.11.034 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 048KA UT WOS:000237944800016 PM 16678060 ER PT J AU Daskivich, TJ Oh, WK AF Daskivich, TJ Oh, WK TI Failure of gonadotropin-releasing hormone agonists with and without sterile abscess formation at depot sites: Insight into mechanisms? SO UROLOGY LA English DT Article ID PRECOCIOUS PUBERTY; THERAPY AB We describe a patient with advanced prostate cancer who failed to achieve testosterone suppression with depot leuprolide after developing sterile abscesses at the injection sites. When the patient was switched to depot goserelin, he did not have any evidence of inflammation at the injection sites, but testosterone suppression again failed. This case suggests variable mechanisms for failure of gonadotropin-releasing hormone agonist therapy and highlights the necessity of prospective testosterone monitoring in patients who have developed sterile abscesses, even if switched to another gonadotropin-releasing hormone agonist. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lanark Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lanark Ctr Genitourinary Oncol, Dana Bldg,Room 1230,44 Binney St, Boston, MA 02115 USA. EM willilam_oh@dcfi.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 5 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2006 VL 67 IS 5 AR 1084.e15 DI 10.1016/j.urology.2005.11.015 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 054PJ UT WOS:000238390800053 ER PT J AU Zhu, CR Ruiz-Perez, F Yang, ZL Mao, Y Hackethal, VL Greco, KM Choy, W Davis, K Butterton, JR Boedeker, EC AF Zhu, CR Ruiz-Perez, F Yang, ZL Mao, Y Hackethal, VL Greco, KM Choy, W Davis, K Butterton, JR Boedeker, EC TI Delivery of heterologous protein antigens via hemolysin or autotransporter systems by an attenuated ler mutant of rabbit enteropathogenic Escherichia coli SO VACCINE LA English DT Article; Proceedings Paper CT 3rd International Conference on Vaccines for Enteric Diseases CY APR 28-30, 2004 CL Montego Bay, JAMAICA DE vaccine vecton; hemolysin; autotransporter ID LIVE-VECTOR VACCINE; SALMONELLA-TYPHIMURIUM; PATHOGENICITY ISLAND; SECRETION SYSTEM; ENTEROCYTE EFFACEMENT; NUCLEOTIDE-SEQUENCE; PEYERS PATCH; STRAINS; TOXIN; ENTERICA AB In this report, we describe the use of an attenuated regulatory mutant of a rabbit enteropathogenic Escherichia coli (rEPEC) as a live vaccine vector to deliver heterologous protein antigens using two dedicated transport systems, a Salmonella autotransporter and the E. coli hemolysin apparatus. We previously reported that an isogeneic ler (LEE encoded regulator) mutant of rEPEC O103:H2 is attenuated and immunogenic in rabbits. We first evaluated the Salmonella autotransporter MisL containing the immunodominant B-cell epitope of the circurnsporozoite protein from Plasmodium falciparum, (NANP)8, fused to the C-terminal translocator domain under the control of the constitutive Tac17 promoter. The rEPEC ler mutant was able to express and to translocate the (NANP)8 passenger peptide to the bacterial surface. We next investigated the delivery of Shiga toxin B subunit (Stx1B) from human enterohemorrhagic E. coli by the rEPEC ler mutant via the MisL autotransporter or the E. coli hemolysin secretion apparatus. The autotransporter and hemolysin plasmids expressed similar levels of Stx1B (30-40 ng/ml/OD600). Only 6% of Stx1B was found in the autotransporter supernatants; the rest was cell-associated, with a small fraction of the Stx1B surface-exposed as determined by immunofluorescence. In contrast, 88% of Stx1B was secreted into culture supernatants by the hemolysin secretion system. In an in vivo study, no significant protection was observed in rabbits inoculated with the ler mutant harboring the Stx1B-autotransporter plasmid following experimental challenge with RDEC-H19A, the prototype rEPEC containing an Stx-converting phage. In contrast, rabbits inoculated with the rEPEC ler mutant containing the Stx1B-hemolysin fusion were partially protected from RDEC-H19A infection as demonstrated by decreased weight loss (p < 0.008) when compared to rabbits inoculated with the parent ler mutant. Our results suggest that attenuated rEPEC are capable of serving as vaccine vectors to express heterologous protein antigens from different cellular locations and deliver these antigens to the intestinal mucosa. With this system, secreted proteins may be more effective than cell-associated antigens in generating protection. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Boedeker, EC (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, 685 W Baltimore St, Baltimore, MD 21201 USA. EM eboedeke@medicine.umaryland.edu FU NIDDK NIH HHS [1R01DK51507] NR 46 TC 14 Z9 16 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 1 PY 2006 VL 24 IS 18 BP 3821 EP 3831 DI 10.1016/j.vaccine.2005.07.024 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 048JT UT WOS:000237944100019 PM 16098637 ER PT J AU Harrington, P Barner, JC Crismon, ML Lawson, KA Mascarenas, C Rascati, KL AF Harrington, P Barner, JC Crismon, ML Lawson, KA Mascarenas, C Rascati, KL TI Demographic and clinical characteristics of patients prescribed antipsychotic (AP) monotherapy in Texas Medicaid SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Texas, Austin, TX 78712 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A74 EP A74 DI 10.1016/S1098-3015(10)64534-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200231 ER PT J AU Harrington, P Barner, JC Crismon, ML Lawson, KA Mascarenas, C Rascati, KL AF Harrington, P Barner, JC Crismon, ML Lawson, KA Mascarenas, C Rascati, KL TI Incident diabetes associated with use of second-generation antipsychotic (SGA) therapy: An evaluation of the impact of dose and treatment indication SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Texas, Austin, TX 78712 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A65 EP A65 DI 10.1016/S1098-3015(10)64506-8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200203 ER PT J AU Johnson, FR Ozdemir, S Mansfield, C Sands, BE Siegel, CA Hass, SL Miller, DW White, TJ AF Johnson, FR Ozdemir, S Mansfield, C Sands, BE Siegel, CA Hass, SL Miller, DW White, TJ TI Weighing treatment benefits against treatment risks: Crohn's disease patients' willingness to accept risk-benefit tradeoffs SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Elan Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A50 EP A50 DI 10.1016/S1098-3015(10)64459-2 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200156 ER PT J AU Pelletier, EM Dembek, CJ Gazelle, GS AF Pelletier, EM Dembek, CJ Gazelle, GS TI Economic outcomes in hepatocellular carcinoma and metastatic liver disease patients: A Medicare perspective SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Boston Sci Corp, Natick, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A108 EP A109 DI 10.1016/S1098-3015(10)64641-4 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200338 ER PT J AU Pelletier, EM Dembek, CJ Gazelle, GS AF Pelletier, EM Dembek, CJ Gazelle, GS TI Economic outcomes in hepatocellular carcinoma and metastatic liver disease patients: A private payer perspective SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Boston Sci Corp, Natick, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A18 EP A18 DI 10.1016/S1098-3015(10)64366-5 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200063 ER PT J AU Yang, M Barner, JC Lawson, KA Rascati, KL Crismon, ML Wilson, JP Worchel, J Mascarenas, J AF Yang, M Barner, JC Lawson, KA Rascati, KL Crismon, ML Wilson, JP Worchel, J Mascarenas, J TI Antipsychotic utilization and treatment-emergent diabetes - Comparison of results with and without propensity scoring SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Texas, Austin, TX 78712 USA. Cent Texas Vet Hlth Care Syst, Austin, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A39 EP A39 DI 10.1016/S1098-3015(10)64425-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200122 ER PT J AU Yang, M Barner, JC Rascati, KL Lawson, KA Wilson, JP Crismon, ML Worchel, J Mascarenas, C AF Yang, M Barner, JC Rascati, KL Lawson, KA Wilson, JP Crismon, ML Worchel, J Mascarenas, C TI Antipsychotic utilization and treatment-emergent diabetes - A methodological comparison using a claims database SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Univ Texas, Austin, TX 78712 USA. Cent Texas Vet Hlth Care Syst, Austin, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2006 VL 9 IS 3 BP A38 EP A39 DI 10.1016/S1098-3015(10)64424-5 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 038MC UT WOS:000237224200121 ER PT J AU Washington, DL Yano, EM Goldzweig, C Simon, B AF Washington, DL Yano, EM Goldzweig, C Simon, B TI VA emergency health care for women: Condition - Critical or stable? SO WOMENS HEALTH ISSUES LA English DT Article ID AFFAIRS MEDICAL-CENTER; VETERANS; DEPARTMENTS AB Background. Veteran's Affairs (VA) facilities have reconfigured themselves to address the health care needs of the growing number of women veterans. However, the challenge of providing comprehensive care to a group that is an extreme minority within VA may still leave gaps in the delivery of necessary health care services. Objectives and methods. We sought to assess the availability of women's health care specialists for emergency gynecologic problems (emergency-GYN) and for emergency mental health conditions specific to women (emergency-WMH), we surveyed the Chief of Staff and senior clinician at each VA site serving 400 or more women veterans. Results. Emergency-GYN expertise was usually available at all times for 39.8% of sites, and only during usual clinic hours for 24.6% of sites. An emergency-WMH specialist was available at all times for 51.7% of sites, and only during usual clinic hours for 31.0% of sites. VA sites that had a separate women's health clinic were more likely to have emergency-GYN expertise available. Sites in regions with higher managed care penetration were less likely to have emergency-WMH specialist availability. Conclusions. Our data suggest a limited availability of specialists for gynecologic and women's mental health emergencies at some VA sites. How this may affect overall quality of care for women in the VA system is unknown. Further work is needed to determine actions clinicians take when expertise is emergently needed for health care issues unique to women. Options for expanding VA availability of such expertise include internal development of women's health expertise and telemedicine access to experts to aid in emergency women's health care decision making. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Va Greater Los Angeles HSR&D Ctr Excellence, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. EM donna.washington@va.gov NR 18 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAY-JUN PY 2006 VL 16 IS 3 BP 133 EP 138 DI 10.1016/j.whi.2005.12.003 PG 6 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 054TL UT WOS:000238401400005 PM 16765289 ER PT J AU Tache, Y Yang, H Miampamba, M Martinez, V Yuan, PQ AF Tache, Y Yang, H Miampamba, M Martinez, V Yuan, PQ TI Role of brainstem TRH/TRH-R1 receptors in the vagal gastric cholinergic response to various stimuli including sham-feeding SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article; Proceedings Paper CT Pavlov Centenary Symposium on Integrative Physiology and Behaviour CY JUN, 2004 CL IP Pavlov Inst Physiol, St Petersburg, RUSSIA HO IP Pavlov Inst Physiol DE TRH; vagus; pChAT; myenteric neurons; gastric acid secretion; dorsal motor nucleus ID THYROTROPIN-RELEASING-HORMONE; DORSAL MOTOR NUCLEUS; ENTERIC NERVOUS-SYSTEM; ACID SECRETORY RESPONSE; RAPHE PALLIDUS NEURONS; TRH ANALOG; INTRACISTERNAL TRH; RAT-BRAIN; FOS EXPRESSION; SUBSTANCE-P AB Pavlov's pioneering work established that sham-feeding induced by sight or smell of food or feeding in dogs with permanent esophagostomy stimulates gastric acid secretion through vagal pathways. Brain circuitries and transmitters involved in the central vagal regulation of gastric function have recently been unraveled. Neurons in the dorsal vagal complex including the dorsal motor nucleus of the vagus (DMN) express thyrotropin-releasing hormone (TRH) receptor and are innervated by TRH fibers originating from TRH synthesizing neurons in the raphe pallidus, raphe obscurus and the parapyramidal regions. TRH injected into the DMN or cisterna, magna increases the firing of DMN neurons and gastric vagal efferent discharge, activates cholinergic neurons in gastric submucosal and myenteric plexuses and induces a vagal-dependent, atropine-sensitive stimulation of gastric secretory (acid, pepsin) and motor functions. TRH antibody or TRH-R1 receptor oligodeoxynucleotide antisense pretreatment in the cisterna magna or DMN abolished vagal-dependent gastric secretory and motor responses to sham-feeding, 2-deoxy-D-glucose, cold exposure and chemical activation of cell bodies in medullary raphe nuclei. TRH excitatory action in the DMN is potentiated by co-released prepro-TRH-(160-169) flanking peptide, Ps4 and 5-HT, and inhibited by a number of peptides involved in the stress/immune response and inhibition of food-intake. These neuroanatomical, electrophysiological and neuropharmacological data are consistent with a physiological role of brainstem TRH in the central vagal stimulation of gastric myenteric cholinergic neurons in response to several vagal dependent stimuli including sham-feeding. (c) 2006 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, CURE, DDR, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), VA Greater Los Angeles Healthcare Syst, CURE, DDR, Digest Dis Res Ctr, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yTache@mednet.ucla.edu RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK 50255, DK 33061, DK 41301]; PHS HHS [R01 30110] NR 122 TC 22 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD APR 30 PY 2006 VL 125 IS 1-2 BP 42 EP 52 DI 10.1016/j.autneu.2006.01.014 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 045PT UT WOS:000237754800007 PM 16520096 ER PT J AU Sakimoto, T Rosenblatt, MI Azar, DT AF Sakimoto, T Rosenblatt, MI Azar, DT TI Laser eye surgery for refractive errors SO LANCET LA English DT Review ID IN-SITU KERATOMILEUSIS; DIFFUSE LAMELLAR KERATITIS; ASSISTED SUBEPITHELIAL KERATECTOMY; EC-5000 EXCIMER-LASER; PHOTOREFRACTIVE KERATECTOMY; EPITHELIAL KERATOMILEUSIS; HYPEROPIC ASTIGMATISM; MODERATE MYOPIA; FOLLOW-UP; HANSATOME MICROKERATOME AB Several laser and non-laser refractive surgical procedures have been used to modify the shape of the cornea and correct myopia, hyperopia, astigmatism, and presbyopia. Introduction of the excimer laser to reshape the cornea has resulted in remarkable developments in the correction of these refractive errors. Combined with other advanced ophthalmological instruments, laser refractive eye surgery has resulted in a substantial rise in the safety, efficacy, and predictability of surgical outcomes. Despite these advances, certain limitations and complications persist. In this review, we describe the history; preoperative assessment, surgical techniques, outcomes, and complications of laser refractive surgery. C1 Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY10101] NR 118 TC 67 Z9 68 U1 0 U2 7 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 29 PY 2006 VL 367 IS 9520 BP 1432 EP 1447 DI 10.1016/S0140-6736(06)68275-5 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 038CI UT WOS:000237195600031 PM 16650653 ER PT J AU Brown, M AF Brown, M TI Toxicological assessments of Gulf War veterans SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE veterans; pesticides; uranium; pyridostigimine bromide; sarin ID AMYOTROPHIC-LATERAL-SCLEROSIS; POSTTRAUMATIC-STRESS-DISORDER; NEUROLOGIC SYMPTOM COMPLEXES; CHRONIC MULTISYMPTOM ILLNESS; CHRONIC-FATIGUE-SYNDROME; SELF-REPORTED EXPOSURES; CHEMICAL WARFARE AGENTS; PERSIAN-GULF; TOKYO SUBWAY; PYRIDOSTIGMINE BROMIDE AB Concerns about unexplained illnesses among veterans of the 1991 Gulf War appeared soon after that conflict ended. Many environmental causes have been suggested, including possible exposure to depleted uranium munitions, vaccines and other drugs used to protect troops, deliberate or accidental exposure to chemical warfare agents and pesticides and smoke from oil-well fires. To help resolve these issues, US and UK governments have sought independent expert scientific advice from prestigious, independent scientific and public health experts, including the US National Academies of Science and the UK Royal Society and Medical Research Council. Their authoritative and independent scientific and medical reviews shed light on a wide range of Gulf War environmental hazards. However, they have added little to our understanding of Gulf War veterans' illnesses, because identified health effects have been previously well characterized, primarily in the occupational health literature. This effort has not identified any new health effects or unique syndromes associated with the evaluated environmental hazards. Nor do their findings provide an explanation for significant amounts of illnesses among veterans of the 1991 Gulf War. Nevertheless, these independent and highly credible scientific reviews have proven to be an effective means for evaluating potential health effects from deployment-related environmental hazards. C1 US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. RP Brown, M (reprint author), US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. EM mbrown1@va.gov NR 104 TC 16 Z9 16 U1 2 U2 4 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 EI 1471-2970 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD APR 29 PY 2006 VL 361 IS 1468 BP 649 EP 679 DI 10.1098/rstb.2006.1825 PG 31 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 030YU UT WOS:000236672100012 PM 16687269 ER PT J AU Haq, E Contreras, MA Giri, S Singh, I Singh, AK AF Haq, E Contreras, MA Giri, S Singh, I Singh, AK TI Dysfunction of peroxisomes in twitcher mice brain: A possible mechanism of psychosine-induced disease SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE psychosine; Krabbe disease; peroxisomes; twitcher mice; neuroinflammation ID BETA-OXIDATION ENZYMES; PROLIFERATOR-ACTIVATED RECEPTORS; GLOBOID-CELL LEUKODYSTROPHY; RAT-LIVER PEROXISOMES; CHAIN FATTY-ACIDS; C6 GLIAL-CELLS; TNF-ALPHA; INFLAMMATORY DISEASE; MURINE MODEL; BIOSYNTHESIS AB Psychosine (galactosylsphingosine) accumulates in the brain of Krabbe disease (KD) patients as well as twitcher mice, a murine model of KD, resulting in loss of oligodendrocytes and myelin. This study documents progressive loss of peroxisomal proteins/functions and induction of expression of inflammatory cytokine TNF-alpha in twitcher brain. The observed decrease in peroxisomal proteins was accompanied by decreased level of peroxisome proliferator-activated receptor-alpha (PPAR-alpha), one of the transcription factors required for expression of peroxisomal protein genes. The role of psychosine in down-regulation of PPAR-alpha activity was further supported by decreased PPAR-alpha mediated PPRE transcriptional activity in cells transfected with PPAR-alpha and PPRE reporters. The psychosine-induced down-regulation of PPAR activity and cell death was attenuated by sPLA(2) inhibitor. Therefore, this study provides the first evidence of peroxisomal abnormality in a lysosomal disorder, suggesting that such dysfunction of peroxisomes may play a role in the pathogenesis of Krabbe disease. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Childrens Res Inst, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. EM singha@musc.edu OI Haq, Ehtishamul/0000-0002-4195-0606 FU NCRR NIH HHS [C06 RR015455, C06 RR018823]; NIA NIH HHS [AG25307]; NINDS NIH HHS [NS-22576, NS-40810, NS34741, NS37766] NR 42 TC 28 Z9 28 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 APR 28 PY 2006 VL 343 IS 1 BP 229 EP 238 DI 10.1016/j.bbrc.2006.02.131 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 030UC UT WOS:000236659300033 PM 16530726 ER PT J AU Giaime, E Sunyach, C Herrant, M Grosso, S Auberger, P McLean, PJ Checler, F da Costa, CA AF Giaime, E Sunyach, C Herrant, M Grosso, S Auberger, P McLean, PJ Checler, F da Costa, CA TI Caspase-3-derived C-terminal product of synphilin-1 displays antiapoptotic function via modulation of the p53-dependent cell death pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; NEUROBLASTOMA SH-SY5Y CELLS; ALPHA-SYNUCLEIN AGGREGATION; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; MOLECULAR PATHWAYS; LEWY BODIES; NEURODEGENERATIVE DISORDERS; NEURONAL CELLS; ANIMAL-MODELS AB Parkinson disease is the second most frequent neurodegenerative disorder after Alzheimer disease. A subset of genetic forms of Parkinson disease has been attributed to alpha-synuclein, a synaptic protein with remarkable chaperone properties. Synphilin-1 is a cytoplasmic protein that has been identified as a partner of alpha-synuclein ( Engelender, S., Kaminsky, Z., Guo, X., Sharp, A. H., Amaravi, R. K., Kleiderlein, J. J., Margolis, R. L., Troncoso, J. C., Lanahan, A. A., Worley, P. F., Dawson, V. L., Dawson, T. M., and Ross, C. A. ( 1999) Nat. Gen. 22, 110-114), but its function remains totally unknown. We show here for the first time that synphilin-1 displays an antiapoptotic function in the control of cell death. We have established transient and stable transfectants overexpressing wild-type synphilin-1 in human embryonic kidney 293 cells, telecephalon-specific murine 1 neurons, and SH-SY5Y neuroblastoma cells, and we show that both cell systems display lower responsiveness to staurosporine and 6-hydroxydopamine. Thus, synphilin-1 reduces procaspase-3 hydrolysis and thereby caspase-3 activity and decreases poly( ADP-ribose) polymerase cleavage, two main indicators of apoptotic cell death. Furthermore, we establish that synphilin-1 drastically reduces p53 transcriptional activity and expression and lowers p53 promoter transactivation and mRNA levels. Interestingly, we demonstrate that synphilin-1 catabolism is enhanced by staurosporine and blocked by caspase-3 inhibitors. Accordingly, we show by transcription/translation assay that recombinant caspase-3 and, to a lesser extent, caspase-6 but not caspase-7 hydrolyze synphilin-1. Furthermore, we demonstrate that mutated synphilin-1, in which a consensus caspase-3 target sequence has been disrupted, resists proteolysis by cellular and recombinant caspases and displays drastically reduced antiapoptotic phenotype. We further show that the caspase-3-derived C-terminal fragment of synphilin-1 was probably responsible for the antiapoptotic phenotype elicited by the parent wild-type protein. Altogether, our study is the first demonstration that synphilin-1 harbors a protective function that is controlled by the C-terminal fragment generated by its proteolysis by caspase-3. C1 Univ Nice Sophia Antipolis, CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097,Equipe Labellisee Fdn Rech Med, F-06560 Valbonne, France. INSERM, Fac Med, U526, Equipe Labellisee Ligue Natl Contre Canc, F-06107 Nice 2, France. Massachusetts Gen Hosp, Dept Neurol, Alzheimer Dis Res Unit, Charlestown, MA 02129 USA. RP Checler, F (reprint author), Univ Nice Sophia Antipolis, CNRS, Inst Pharmacol Mol & Cellulaire, UMR6097,Equipe Labellisee Fdn Rech Med, 660 Route Lucioles, F-06560 Valbonne, France. EM checler@ipmc.cnrs.fr; acosta@ipmc.cnrs.fr RI alves da Costa, cristine/G-8075-2011; Checler, Frederic/C-1241-2009; AUBERGER, Patrick/G-1491-2013 OI alves da Costa, cristine/0000-0002-7777-005X; Checler, Frederic/0000-0003-2098-1750; AUBERGER, Patrick/0000-0002-2481-8275 NR 64 TC 28 Z9 28 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 APR 28 PY 2006 VL 281 IS 17 BP 11515 EP 11522 DI 10.1074/jbc.M508619200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 035GH UT WOS:000236988100013 PM 16495229 ER PT J AU Swenson, ER AF Swenson, ER TI Carbonic anhydrase inhibitors and hypoxic pulmonary vasoconstriction SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE carbonic anhydrase; inhibition; hypoxia; acute mountain sickness; pulmonary artery smooth muscle; high altitude pulmonary edema; acetazolamide; benzolamide; ethoxzolamide ID ARTERIAL SMOOTH-MUSCLE; ACUTE MOUNTAIN-SICKNESS; INTRACELLULAR PH; TEMPORAL HETEROGENEITY; ACETAZOLAMIDE; EDEMA; VENTILATION; INCREASES; PERFUSION; PRESSURE AB Acetazolamide and other related carbonic anhydrase (CA) inhibitors have had a long history of effectiveness in prevention and treatment of acute mountain sickness (AMS) and remain the standard of care for this indication. Despite many decades of CA inhibitor use for AMS, the possibility has never been seriously entertained that these drugs might also afford protection against high altitude pulmonary edema (HAPE). In this paper, I will present our evidence and supporting data of others, that acetazolamide has inhibitory effects on the hypoxic response of the Pulmonary circulation that may be useful in HAPE. Data from pulmonary artery smooth muscle cells, isolated perfused lungs, and live unanethetized animals all point to a potent reduction in hypoxic pulmonary vasoconstriction (HPV) by acetazolamide that may have clinical utility in HAPE and possibly other pulmonary hypertensive disorders. Astonishingly, the efficacy of acetazolamide as a HPV inhibitor does not appear to be related to carbonic anhydrase inhibition, since other potent CA inhibitors have no effect on HPV either in the conscious dog or on hypoxic calcium (Ca2+) signalling in rat Pulmonary artery smooth muscle cells, despite enzyme presence in these cells. Although we have not yet determined the mechanism of action for acetazolamide in HPV, we have ruled out actions on membrane L-type Ca2+ channels, normoxic and hypoxic membrane potential and rho-kinase activation. Based upon these negative findings in isolated pulmonary artery smooth muscle cells and preliminary data in Ca2+ free media we propose that acetazolamide may act at the level of Ca2+ release from the sarcoplasmic reticulum, a process which initiates and amplifies cell membrane Ca2+ channel opening. In further work, we have developed and will use a methylated analog of acetazolamide to yield a molecule lacking CA inhibiting activity, but which in most other respects (size, pK(a), heterocyclic ring structure, electrostatic charge distribution) is equivalent to acetazolamide. Published by Elsevier B.V. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Swenson, ER (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. EM eswenson@umashington.edu FU NHLBI NIH HHS [HL-24163, HL-67191] NR 31 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD APR 28 PY 2006 VL 151 IS 2-3 BP 209 EP 216 DI 10.1016/j.resp.2005.10.011 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 041ZQ UT WOS:000237496600012 PM 16376158 ER PT J AU Hetz, C Bernasconi, P Fisher, J Lee, AH Bassik, MC Antonsson, B Brandt, GS Iwakoshi, NN Schinzel, A Glimcher, LH Korsmeyer, SJ AF Hetz, C Bernasconi, P Fisher, J Lee, AH Bassik, MC Antonsson, B Brandt, GS Iwakoshi, NN Schinzel, A Glimcher, LH Korsmeyer, SJ TI Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1 alpha SO SCIENCE LA English DT Article ID ENDOPLASMIC-RETICULUM; MESSENGER-RNA; ER STRESS; TRANSCRIPTION FACTOR; CELL-DEATH; APOPTOSIS; XBP-1; IRE1; ACTIVATION; BIOGENESIS AB Accumulation of misfolded protein in the endoplasmic reticulum (ER) triggers an adaptive stress response-termed the unfolded protein response (UPR)-mediated by the ER transmembrane protein kinase and endoribonuclease inositol-requiring enzyme-1 alpha (IRE1 alpha). We investigated UPR signaling events in mice in the absence of the proapoptotic BCL-2 family members BAX and BAK [double knockout (DKO)]. DKO mice responded abnormally to tunicamycin-induced ER stress in the liver, with extensive tissue damage and decreased expression of the IRE1 substrate X-box-binding protein 1 and its target genes. ER-stressed DKO cells showed deficient IRE1a signaling. BAX and BAK formed a protein complex with the cytosolic domain of IRE1 alpha that was essential for IRE1 alpha activation. Thus, BAX and BAK function at the ER membrane to activate IRE1 alpha signaling and to provide a physical link between members of the core apoptotic pathway and the UPR. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Serono Pharmaceut Res Inst, CH-1228 Plan Les Ouates, Switzerland. Brandeis Univ, Rosenstiel Ctr, Dept Biochem, Waltham, MA 02454 USA. Brandeis Univ, Rosenstiel Ctr, Dept Chem, Waltham, MA 02454 USA. RP Hetz, C (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM chetz@hsph.harvard.edu; lglimche@hsph.harvard.edu RI Hetz, Claudio/I-1900-2013 OI Hetz, Claudio/0000-0001-7724-1767 FU NCI NIH HHS [CA100707, R37 CA50239, P01 CA92625]; NIAID NIH HHS [P01 AI56296, R01 AI32412] NR 32 TC 355 Z9 368 U1 3 U2 24 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 28 PY 2006 VL 312 IS 5773 BP 572 EP 576 DI 10.1126/science.1123480 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 039HN UT WOS:000237296700044 PM 16645094 ER PT J AU Wolpin, BM Sahani, DV Zhu, AX D'Andrea, AD Hasserjian, RP Chabner, B AF Wolpin, BM Sahani, DV Zhu, AX D'Andrea, AD Hasserjian, RP Chabner, B TI Case 13-2006: A 50-year-old man with a painful bone mass and lesions in the liver - Fanconi's anemia and hepatocellular carcinoma, metastatic to bone. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; CANCER; REGISTRY; CHEMOEMBOLIZATION; DIAGNOSIS C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiat Oncol & Pediat, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wolpin, BM (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 28 TC 2 Z9 2 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 27 PY 2006 VL 354 IS 17 BP 1828 EP 1837 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 036NF UT WOS:000237077100011 ER PT J AU Olson, IR Page, K Moore, KS Chatterjee, A Verfaellie, M AF Olson, IR Page, K Moore, KS Chatterjee, A Verfaellie, M TI Working memory for conjunctions relies on the medial temporal lobe SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; associative; amnesia; visual; memory; long-term; short-term; chunking; binding ID SHORT-TERM-MEMORY; RECOGNITION MEMORY; HUMAN HIPPOCAMPUS; ITEM RECOGNITION; AMNESIC PATIENTS; INFORMATION; LESIONS; FMRI; ASSOCIATIONS; ACTIVATION AB A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays. C1 Univ Penn, Ctr Cognit Neurosci, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Olson, IR (reprint author), Univ Penn, Ctr Cognit Neurosci, 3720 Walnut St,Room B51, Philadelphia, PA 19104 USA. EM iolson@psych.upenn.edu RI Moore, Katherine/B-8445-2009; OI Verfaellie, Mieke/0000-0001-5535-4584 FU NIMH NIH HHS [R01 MH057681, R01 MH071615, R01 MH071615-01] NR 43 TC 208 Z9 208 U1 2 U2 21 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 26 PY 2006 VL 26 IS 17 BP 4596 EP 4601 DI 10.1523/JNEUROSCI.1923-05.2006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 039AK UT WOS:000237271400018 PM 16641239 ER PT J AU Hallett, PJ Spoelgen, R Hyman, BT Standaert, DG Dunah, AW AF Hallett, PJ Spoelgen, R Hyman, BT Standaert, DG Dunah, AW TI Dopamine D-1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptors; NMDA receptors; dopamine receptors; striatal neurons; tyrosine phosphorylation; receptor trafficking ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; POSTSYNAPTIC DENSITY FRACTION; SYNAPTIC PLASTICITY; PARKINSONS-DISEASE; SURFACE EXPRESSION; GLUTAMATE RECEPTORS; RAT-BRAIN; PHOSPHATASE STEP; DORSAL STRIATUM AB Interactions between dopaminergic and glutamatergic afferents in the striatum are essential for motor learning and the regulation of movement. An important mechanism for these interactions is the ability of dopamine, through D-1 receptors, to potentiate NMDA glutamate receptor function. Here we show that, in striatal neurons, D-1 receptor activation leads to rapid trafficking of NMDA receptor subunits, with increased NR1 and NR2B subunits in dendrites, enhanced coclustering of these subunits with the postsynaptic density scaffolding molecule postsynaptic density-95, and increased surface expression. The dopamine D-1 receptor-mediated NMDA receptor trafficking is blocked by an inhibitor of tyrosine kinases. Blockers of tyrosine phosphatases also induce NMDA subunit trafficking, but this effect is nonselective and alters both NR2A- and NR2B-containing receptors. Furthermore, tyrosine phosphatase inhibition leads to the clustering of tyrosine-phosphorylated NR2B subunit along dendritic shafts. Our findings reveal that D-1 receptor activation can potentiate striatal NMDA subunit function by directly promoting the surface insertion of the receptor complexes. This effect is regulated by the reciprocal actions of protein tyrosine phosphatases and tyrosine kinases. Modification of these pathways may be a useful therapeutic target for Parkinson's disease and other basal ganglia disorders in which abnormal function of striatal NMDA receptors contributes to the symptoms of the diseases. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. Harvard Univ, MassGen Inst Neurodegenerat Dis, Sch Med, Charlestown, MA 02129 USA. RP Dunah, AW (reprint author), Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, 114 16th St,B114-2125, Charlestown, MA 02129 USA. EM dunah@helix.mgh.harvard.edu OI Hallett, Penelope/0000-0002-8858-9096; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS34361, K01NS049006] NR 69 TC 135 Z9 139 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 26 PY 2006 VL 26 IS 17 BP 4690 EP 4700 DI 10.1523/JNEUROSCI.0792-06.2006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 039AK UT WOS:000237271400029 PM 16641250 ER PT J AU Goess, BC Hannoush, RN Chan, LK Kirchhausen, T Shair, MD AF Goess, BC Hannoush, RN Chan, LK Kirchhausen, T Shair, MD TI Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DIVERSITY-ORIENTED SYNTHESIS; TO-GOLGI TRANSPORT; NATURAL-PRODUCTS; COMBINATORIAL CHEMISTRY; CHEMICAL GENETICS; ORGANIC-SYNTHESIS; DRUG DISCOVERY; LIVING CELLS; BREFELDIN-A; ONE-BEAD AB Split-and-pool synthesis of a 10,000-membered library of molecules resembling the natural product carpanone has been achieved. The synthesis features development of solid-phase multicomponent reactions between nitrogen nucleophiles, enones, and hydroxylamines, and a solid-phase application of the Huisgen cycloaddition affording substituted triazoles. The synthesis was performed in high-capacity (500 pm) polystyrene beads using a one bead-one stock solution strategy that enabled phenotypic screens of the resulting library. Using whole-cell fluorescence imaging, we discovered a series of molecules from the carpanone-based library that inhibit exocytosis from the Golgi apparatus. The most potent member of this series has an IC50 of 14 mu M. We also report structure-activity relationships for the molecules exhibiting this interesting phenotype. These inhibitors of exocytosis may be useful reagents for the study of vesicular traffic. C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Harvard Inst Chem & Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM shair@chemistry.harvard.edu FU NIGMS NIH HHS [P01 GM062566, P01 GM62566-05, R01 GM075252] NR 47 TC 49 Z9 50 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 26 PY 2006 VL 128 IS 16 BP 5391 EP 5403 DI 10.1021/ja056338g PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 037CU UT WOS:000237125100036 PM 16620111 ER PT J AU Elliott, DD Pitman, MB Bloom, L Faquin, WC AF Elliott, DD Pitman, MB Bloom, L Faquin, WC TI Fine-needle aspiration biopsy of Hurthle cell lesions of the thyroid gland - A cytomorphologic study of 139 cases with statistical analysis SO CANCER CYTOPATHOLOGY LA English DT Article DE fine-needle aspiration; thyroid; Hurthle cell; neoplasm; statistical ID INCREASED RISK; TUMORS; DIAGNOSIS; NEOPLASM; MALIGNANCY; CARCINOMA AB BACKGROUND. Lesions of the thyroid gland composed of Hurthle cells encompass pathologic entities ranging from hyperplastic nodules with Hurthle cell metaplasia to Hurthle cell carcinomas. The cytologic distinction between these entities can be diagnostically challenging. Many cytologic features of Hurthle cell lesions that distinguish neoplastic Hurthle cell lesions requiring surgery from those that are benign and nonneoplastic have been described, but with variable usefulness. This is due, in part, to the small numbers of cases examined in previous studies and the limited application of statistical analysis. A morphologic study was made of 139 Hurthle cell lesions of the thyroid gland and statistical analysis applied to identify a set of cytomorphologic features that distinguish benign Hurthle cell lesions (BHCL) from Hurthle cell neoplasms (HCN). METHODS. Fine-needle aspiration biopsies"(FNABs) of thyroid nodules with a predominant Hurthle cell component and corresponding histologic followup were included in the study. Cases were divided into BHCL and HCN groups on the basis of the histologic diagnosis. All cases were reviewed to assess the following 14 cytologic features: overall cellularity, cytoarchitecture, percentage of Hurthle cells, percentage of single cells, percentage of follicular cells observed as naked Hurthle cell nuclei, background colloid, chronic inflammation, cystic change, transgressing blood vessels (TBV), intracytoplasmic lumina, presence of multinucleated Hurthle cells, nuclear to cytoplasmic ratio, nuclear pleomorphism/atypia, and nucleolar prominence. The results were evaluated by using univariate and stepwise logistic regression (SLR) analysis; statistical significance was achieved at P-values < 0.05. RESULTS. One hundred thirty-nine FNAB specimens, corresponding to 56 HCN and 83 BHCL, fulfilled the study criteria. Six of the 14 cytologic features evaluated were shown by univariate analysis to be statistically significant in predicting HCN: nonmacrofollicular architecture (P < 0.001), absence of background colloid (P < 0.001), absence of chronic inflammation (P < 0.001), presence of TBV (P < 0.001), > 90% Hurthle cells (P < 0.001), and > 10% single Hurthle cells (P = 0.014). The first four of these features were also shown to be statistically significant in the SLR analysis (P = 0.005, 0.010, 0.016, and 0.045, respectively), and when all four of these features were present HCN was correctly identified 86% of the time. CONCLUSIONS. In the current study of 139 FNAB specimens of thyroid Hurthle cell nodules, 14 cytologic features were examined and 6 were found to be statistically significant in identifying HCN. The following four features, when found in combination, were found to be highly predictive of HCN: nonmacrofollicular architecture, absence of colloid, absence of inflammation, and presence of TBV. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Tennessee, Hlth Sci Ctr, Dept Clin Lab Sci, Memphis, TN USA. RP Elliott, DD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Unit 85,1515 Holcombe Blvd, Houston, TX 77030 USA. EM danellio@mdanderson.org NR 24 TC 51 Z9 52 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2006 VL 108 IS 2 BP 102 EP 109 DI 10.1002/cncr.21716 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 036NM UT WOS:000237077800004 PM 16453320 ER PT J AU Chandan, VS Faquin, WC Wilbur, DC Khurana, KK AF Chandan, VS Faquin, WC Wilbur, DC Khurana, KK TI The utility of GLUT-1 immunolocalization in cell blocks - An adjunct to the fine needle aspiration diagnosis of cystic squamous lesions of the head and neck SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-of-Cytopathology CY NOV 04-09, 2005 CL San Diego, CA SP Amer Soc Cytopathol DE head; neck; squamous; carcinoma; benign; GLUT-1; aspiration; cytology ID ERYTHROCYTE GLUCOSE-TRANSPORTER; P53 IMMUNOLOCALIZATION; CARCINOMA; EXPRESSION; BIOPSY; BENIGN; TUMORS; NODES AB BACKGROUND. Cytologic distinction of metastatic cystic squamous cell carcinoma (SCC) from benign squamous cell lesions, especially the ones with superimposed inflammatory atypia, can be very challenging. The authors evaluated the usefulness of glucose transporter-1 (GLUT-1) immunostaining as an adjunct to fine-needle aspirations of squamous lesions of the head and neck. METHODS. Immunohistochemical staining for GLUT-1 was performed on paraffin-embedded cell blocks of 28 cases with the following cytologic diagnoses: 1) metastatic SCC (11 cases); 2) atypical squamous cells, South CarolinaC cannot be excluded (6 cases); and 3) cytologic findings consistent with branchial cleft cyst (BCC) (11 cases). RESULTS. All 11 cases with an unequivocal cytologic diagnosis of metastatic SCC were positive for GLUT-1. Tissue follow-up confirmed metastatic SCC in all 11 cases. The squamous cells in all 11 cases with cytologic findings consistent with BCC were negative for GLUT-1; tissue follow-up confirmed diagnoses of BCC in 8 cases. In the remaining 3 cases, excision was not performed, and, clinically, no recurrences were identified at 28, 20, and 16 months of follow-up. Of the 6 cases with cytologic diagnosis of atypical squamous cells, 3 were negative and 3 were positive for GLUT-1. Subsequent excisional biopsies in these cases revealed 4 cases of metastatic SCC (3 positive and 1 negative for GLUT-1), 1 case of BCC (negative for GLUT-1), and 1 case of thyroglossal duct cyst (negative for GLUT-1). CONCLUSION. GLUT-1 immunostaining is a useful adjunct in differentiating benign and malignant squamous lesions in cell-block material. Although negative staining for GLUT-1 does not exclude malignancy, positive immunoreactivity for GLUT-1 may aid in accurate diagnosis of malignancy in cytomorphologically equivocal squamous lesions of the head and neck. C1 SUNY Upstate Med Univ, Dept Pathol, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Khurana, KK (reprint author), SUNY Upstate Med Univ, Dept Pathol, 750 E Adams St, Syracuse, NY 13210 USA. EM khuranak@upstate.edu RI Chandan, Vishal/K-8860-2015 NR 20 TC 11 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2006 VL 108 IS 2 BP 124 EP 128 DI 10.1002/cncr.21714 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 036NM UT WOS:000237077800008 PM 16435376 ER PT J AU Grafton, ST Turner, RS Desmurget, M Bakay, R Delong, M Vitek, J Crutcher, M AF Grafton, ST Turner, RS Desmurget, M Bakay, R Delong, M Vitek, J Crutcher, M TI Normalizing motor-related brain activity - Subthalamic nucleus stimulation in Parkinson disease SO NEUROLOGY LA English DT Article ID HIGH-FREQUENCY STIMULATION; INTERNAL GLOBUS-PALLIDUS; ASSOCIATION-CORTEX; BASAL GANGLIA; FLOW CHANGES; MOVEMENTS; PET; PALLIDOTOMY; PERFORMANCE; INHIBITION AB Objective: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent. Methods: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation. Results: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia. Conclusions: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity. C1 Dartmouth Coll, Ctr Cognit Neurosci, Hanover, NH 03755 USA. Univ Calif San Francisco, Sch Med, Dept Neurosurg, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. INSERM, Unite 534, Lyon, France. Chicago Inst Neurosurg & Neurores, Chicago, IL 60614 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. RP Grafton, ST (reprint author), Dartmouth Coll, Ctr Cognit Neurosci, 6162 Moore Hall, Hanover, NH 03755 USA. EM scott.t.grafton@dartmouth.edu RI Turner, Robert/A-9695-2008 OI Turner, Robert/0000-0002-6074-4365 FU NINDS NIH HHS [NS33504, NS37470, R01 NS044551-01, R01 NS044551] NR 44 TC 91 Z9 92 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2006 VL 66 IS 8 BP 1192 EP 1199 DI 10.1212/01.wnl.0000214237.58321.c3 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 036ER UT WOS:000237054300013 PM 16636237 ER PT J AU Pasinetti, GM Ungar, LH Lange, DJ Yemul, S Deng, H Yuan, X Brown, RH Cudkowicz, ME Newhall, K Peskind, E Marcus, S Ho, L AF Pasinetti, GM Ungar, LH Lange, DJ Yemul, S Deng, H Yuan, X Brown, RH Cudkowicz, ME Newhall, K Peskind, E Marcus, S Ho, L TI Identification of potential CSF biomarkers in ALS SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; NERVE GROWTH-FACTOR; CYSTATIN-C; BUNINA BODIES; CEREBROSPINAL-FLUID; SERUM; MORTALITY; CREATINE AB Background: The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis. Objective: To determine if there is a specific protein profile in the CSF that distinguishes patients with ALS from those with purely motor peripheral neuropathy (PN) and healthy control subjects. Methods: CSF obtained from patients with ALS, disease controls ( patients with other neurologic disorders), and normal controls were analyzed using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomics technique. Biomarker sensitivity and specificity was calculated with receiver operating characteristic curve methodology. ALS biomarkers were purified and sequence identified by mass spectrometry-directed peptide sequencing. Results: In initial proteomic discovery studies, three protein species (4.8-, 6.7-, and 13.4-kDa) that were significantly lower in concentration in the CSF from patients with ALS (n = 36) than in normal controls (n = 21) were identified. A combination of three protein species (the "three-protein" model) correctly identified patients with ALS with 95% accuracy, 91% sensitivity, and 97% specificity from the controls. Independent validation studies using separate cohorts of ALS (n = 13), healthy control (n = 25), and PN (n = 7) subjects confirmed the ability of the three CSF protein species to separate patients with ALS from other diseases. Protein sequence analysis identified the 13.4-kDa protein species as cystatin C and the 4.8-kDa protein species as a peptic fragment of the neurosecretory protein VGF. Conclusion: Additional application of a "three-protein" biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS. C1 Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Neurol, MDA ALS Program, New York, NY 10029 USA. Rockefeller Univ, Proteom Resource Ctr, New York, NY 10021 USA. Bronx Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. Univ Penn, Dept Computat & Informat Sci, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Boston, MA 02114 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, VA Mental Illness Res Educ & Clin Ctr, Seattle, WA 98104 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, Neuroinflammat Res Labs, 1 Gustave L Levy Pl,Box 1668, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIA NIH HHS [AG02219] NR 30 TC 116 Z9 122 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2006 VL 66 IS 8 BP 1218 EP 1222 DI 10.1212/01.wnl.0000203129.82104.07 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 036ER UT WOS:000237054300017 PM 16481598 ER PT J AU Nguyen, TN Rordorf, G Schwamm, LH Smith, EE AF Nguyen, TN Rordorf, G Schwamm, LH Smith, EE TI MRI contrast extravasation with enlarging hyperacute thrombolysis-related hemorrhage SO NEUROLOGY LA English DT Editorial Material ID INTRACEREBRAL HEMORRHAGE C1 Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. CHU Montreal, Notre Dame Hosp, Dept Radiol, Montreal, PQ, Canada. Harvard Univ, Sch Med, Boston, MA USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, MGH Stroke Serv, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 25 PY 2006 VL 66 IS 8 BP E30 EP E31 DI 10.1212/01.wnl.0000208439.31635.96 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 036ER UT WOS:000237054300055 PM 16636225 ER PT J AU Das, H Kumar, A Lin, ZY Patinol, WD Hwang, PM Feinberg, MW Majumder, PK Jain, MK AF Das, H Kumar, A Lin, ZY Patinol, WD Hwang, PM Feinberg, MW Majumder, PK Jain, MK TI Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inflammation; transcription; transcriptional factor; NF-kappa B; activator protein 1 ID NF-KAPPA-B; T-CELL QUIESCENCE; TRANSCRIPTION FACTOR; IN-VIVO; BETA-THALASSEMIA; FACTOR EKLF; INFLAMMATION; GENE; ATHEROSCLEROSIS; INHIBITION AB The mechanisms regulating activation of monocytes remain incompletely understood. Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes is reduced by cytokine activation or differentiation. Consistent with this observation, KLF2 expression in circulating monocytes is reduced in patients with chronic inflammatory conditions such as coronary artery disease. Adenoviral overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short interfering RNA-mediated reduction in KLF2 increased inflammatory gene expression. Reconstitution of immunodeficient mice with KLF2-overexpressing monocytes significantly reduced carrageenan-induced acute paw edema formation. Mechanistically, KLF2 inhibits the transcriptional activity of both NF-kappa B and activator protein 1, in part by means of recruitment of transcriptional coactivator p300/CBP-associated factor. These observations identify KLF2 as a novel negative regulator of monocytic activation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Cardiovasc Transcript Biol,Cardiovasc Div, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20824 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jain, MK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Program Cardiovasc Transcript Biol,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM mjain@rics.bwh.harvard.edu FU NHLBI NIH HHS [HL76754, F32 HL078183, F32 HL78183, HL67755, HL69477, HL72952, HL75427, K08 HL067755, P01 HL048743, P01 HL48743, R01 HL069477, R01 HL072952, R01 HL075427, R01 HL076754] NR 29 TC 108 Z9 116 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 2006 VL 103 IS 17 BP 6653 EP 6658 DI 10.1073/pnas.0508235103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000043 PM 16617118 ER PT J AU Gesta, S Bluher, M Yamamoto, Y Norris, AW Berndt, J Kralisch, S Boucher, J Lewis, C Kahn, CR AF Gesta, S Bluher, M Yamamoto, Y Norris, AW Berndt, J Kralisch, S Boucher, J Lewis, C Kahn, CR TI Evidence for a role of developmental genes in the origin of obesity and body fat distribution SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adipose tissue; gene expression; subcutaneous; intraabdominal ID SUBCUTANEOUS ADIPOSE-TISSUE; PARTIAL LIPODYSTROPHY; ADIPOCYTE DIFFERENTIATION; EXPRESSION PATTERNS; REGIONAL ADIPOSITY; ANATOMIC SITE; RISK-FACTORS; MEN; MOUSE; RECEPTOR AB Obesity, especially central obesity, is a hereditable trait associated with a high risk for development of diabetes and metabolic disorders. Combined gene expression analysis of adipocyte- and preadipocyte-containing fractions from intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot-specific differences in expression of multiple genes involved in embryonic development and pattern specification. These differences were intrinsic and persisted during in vitro culture and differentiation. Similar depot-specific differences in expression of developmental genes were observed in human subcutaneous versus visceral adipose tissue. Furthermore, in humans, several genes exhibited changes in expression that correlated closely with body mass index and/or waist/hip ratio. Together, these data suggest that genetically programmed developmental differences in adipocytes and their precursors in different regions of the body play an important role in obesity, body fat distribution, and potential functional differences between internal and subcutaneous adipose tissue. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu OI Norris, Andrew/0000-0001-8396-9543 FU NICHD NIH HHS [HD027748, K12 HD027748]; NIDDK NIH HHS [K08DK064906, DK60837, K08 DK064906, R01 DK033201, R01 DK060837, R01 DK33201] NR 53 TC 292 Z9 300 U1 6 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 25 PY 2006 VL 103 IS 17 BP 6676 EP 6681 DI 10.1073/pnas.0601752103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 037MM UT WOS:000237151000047 PM 16617105 ER PT J AU Mallik, S Spertus, JA Reid, KJ Krumholz, HM Rumsfeld, JS Weintraub, WS Agarwal, P Santra, M Bidyasar, S Lichtman, JH Wenger, NK Vaccarino, V AF Mallik, S Spertus, JA Reid, KJ Krumholz, HM Rumsfeld, JS Weintraub, WS Agarwal, P Santra, M Bidyasar, S Lichtman, JH Wenger, NK Vaccarino, V CA PREMIER Registry Investigators TI Depressive symptoms after acute myocardial infarction - Evidence for highest rates in younger women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SEX-DIFFERENCES; MORTALITY; EVENTS; HEALTH; PREVALENCE; RECOVERY; DISEASE; GENDER; IMPACT; HEART AB Background: Depression is common in patients hospitalized with acute myocardial infarction ( AMI). In the community, younger women are uniquely prone to depression. Whether younger women are also more likely to have depression during hospitalization with AMI is unknown. Methods: A total of 2498 AMI patients ( 1284 patients <= 60 years; 814 women and 1684 men) were enrolled from 19 US centers in the Prospective Registry Evaluating Outcomes After Myocardial Infarction: Events and Recovery ( PREMIER) study between January 2003 and June 2004. Depression was assessed at the time of hospitalization and was defined as a Primary Care Evaluation of Mental Disorders Brief Patient Health Questionnaire (PHQ) score of 10 or higher. Results: Younger ( <= 60 years) patients had higher mean PHQ scores than older patients ( 6.4 vs 5.0; P <. 001) and women had higher mean PHQ scores than men ( 6.8 vs 5.2; P <. 001). When stratified by both age and sex, younger women had the highest PHQ scores ( 8.2; P <. 001 for the sex-age interaction). The prevalence of depression was 40% in women 60 years or younger, 21% in women older than 60, 22% in men 60 or younger, and 15% in men older than 60. In a logistic model adjusted for study center, race, medical history, and coronary heart disease risk factors, the odds of depression for women 60 years or younger were significantly higher than for the other sex-age groups and were 3.1 times higher than the reference group of men older than 60 years. Conclusions: The prevalence of depression is high in younger women with AMI. Because depression after AMI has been associated with adverse outcomes, younger women, a high-risk group compared with men, may particularly benefit from aggressive screening and treatment of post-AMI depression. C1 Emory Univ, Sch Med, Dept Med, Div Gen Med, Atlanta, GA 30303 USA. Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30303 USA. Mid Amer Heart Inst, Kansas City, MO USA. Yale Univ, Sch Med, Sect Cardiovasc Med, Dept Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Mallik, S (reprint author), Emory Univ, Sch Med, Dept Med, Div Gen Med, Room 473,Fac Off Bldg,49 Jesse Hill Jr Dr, Atlanta, GA 30303 USA. FU NCCDPHP CDC HHS [K01-DP000085-01]; NCRR NIH HHS [MO1-RR00039, K12RR17643]; NHLBI NIH HHS [K24HL077506, R01 HL68630]; NIA NIH HHS [R01 AG026255] NR 22 TC 80 Z9 85 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 24 PY 2006 VL 166 IS 8 BP 876 EP 883 DI 10.1001/archinte.166.8.876 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 035UA UT WOS:000237026000007 PM 16636213 ER PT J AU Drubin, DA Garakani, AM Silver, PA AF Drubin, David A. Garakani, Arman M. Silver, Pamela A. TI Motion as a phenotype: the use of live-cell imaging and machine visual screening to characterize transcription-dependent chromosome dynamics SO BMC CELL BIOLOGY LA English DT Article ID RNA EXPORT MACHINERY; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; IN-VIVO; CHROMATIN ORGANIZATION; NUCLEAR COMPARTMENTS; FLUORESCENT PROTEIN; GENE-EXPRESSION; SAGA COMPLEX; GENOME AB Background: Gene transcriptional activity is well correlated with intra-nuclear position, especially relative to the nuclear periphery, which is a region classically associated with gene silencing. Recently however, actively transcribed genes have also been found localized to the nuclear periphery in the yeast Saccharomyces cerevisiae. When genes are activated, they become associated with the nuclear pore complex ( NPC) at the nuclear envelope. Furthermore, chromosomes are not static structures, but exhibit constrained diffusion in real-time, live-cell studies of particular loci. The relationship of chromosome motion with transcriptional activation and active-gene recruitment to the nuclear periphery has not yet been investigated. Results: We have generated a yeast strain that enables us to observe the motion of the galactose-inducible GAL gene locus relative to the nuclear periphery in real-time under transcriptionally active and repressed conditions. Using segmented geometric particle tracking, we show that the repressed GAL locus undergoes constrained diffusive movement, and that transcriptional induction with galactose is associated with an enrichment in cells with GAL loci that are both associated with the nuclear periphery and much more constrained in their movement. Furthermore, we report that the mRNA export factor Sac3 is involved in this galactose-induced enrichment of GAL loci at the nuclear periphery. In parallel, using a novel machine visual screening technique, we find that the motion of constrained GAL loci correlates with the motion of the cognate nuclei in galactose-induced cells. Conclusion: Transcriptional activation of the GAL genes is associated with their tethering and motion constraint at the nuclear periphery. We describe a model of gene recruitment to the nuclear periphery involving gene diffusion and the mRNA export factor Sac3 that can be used as a framework for further experimentation. In addition, we applied to the analysis of chromosome motion a machine visual screening approach that used unbiased visual data rather than segmented geometric data. This novel analytical approach will allow for high-throughput study of processes that can be monitored via alterations in chromosome motion and connectivity with the nuclear periphery. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Reify Corp, Cambridge, MA USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM david_drubin@hms.harvard.edu; arman@reifycorp.com; pamela_silver@hms.harvard.edu NR 46 TC 29 Z9 30 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD APR 24 PY 2006 VL 7 AR 19 DI 10.1186/1471-2121-7-19 PG 12 WC Cell Biology SC Cell Biology GA 060EK UT WOS:000238785000001 PM 16635267 ER PT J AU de Gelder, B Hadjikhani, N AF de Gelder, B Hadjikhani, N TI Non-conscious recognition of emotional body language SO NEUROREPORT LA English DT Article DE action representation; blindsight; emotion; non-conscious emotion; whole body expression ID BIOLOGICAL MOTION; RIGHT AMYGDALA; BRAIN; FEAR; EXPRESSIONS; PERCEPTION; SYSTEMS; CORTEX; FACES AB Patients with cortical blindness can reliably perceive some facial expressions even if they are unaware of their percept. We examined whether emotional body language may also be recognized in the absence of the primary visual cortex and without conscious stimulus perception. We presented emotional and neutral body images in the blind field of a patient with unilateral striate cortex damage. Using functional magnetic resonance imaging, we measured activation following presentation to the blind hemifield of whole body images (happy, neutral) with the face blurred. Unseen happy body images selectively activated area MT and the pulvinar nucleus of the thalamus, while unseen instrumental neutral body images activated the premotor cortex. Our results show that in the absence of the striate cortex implicit bodily emotion perception may be possible. C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, Wardelaan 2, NL-5000 LE Tilburg, Netherlands. EM degelder@nmr.mgh.harvard.edu RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 FU NINDS NIH HHS [R01 NS44824-01] NR 26 TC 46 Z9 47 U1 2 U2 22 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 24 PY 2006 VL 17 IS 6 BP 583 EP 586 DI 10.1097/00001756-200604240-00006 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 042LK UT WOS:000237529300006 PM 16603916 ER PT J AU Xu, Y Kitada, M Yamaguchi, M Dezawa, M Ide, C AF Xu, Y Kitada, M Yamaguchi, M Dezawa, M Ide, C TI Increase in bFGF-responsive neural progenitor population following contusion injury of the adult rodent spinal cord SO NEUROSCIENCE LETTERS LA English DT Article DE spinal cord injury; neural progenitor cell; bFGF; radial glia; glial scar ID FIBROBLAST GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; STEM-CELLS; PROLIFERATION; AXONS; CNS; DIFFERENTIATION; NEUROGENESIS; REGENERATION; ASTROCYTES AB The number of neural progenitor cells, especially nestin(+) cells or BrdU-uptake cells is sparse in the normal adult rodent spinal cord. However, in the present study, we show that after spinal cord injury (SCI), many ordinarily quiescent cells were activated to become nestin(+) and undergo mitosis (BrdU(+)) in the ependymal layer as well as in the parenchyma of the spinal cord. Nestin(+) cells and BrdU(+) cells were in most cases immunohistochemically GFAP(+), some of which displayed radial glial cell morphology and partly participated in the border formation of the lesion. The culturing of injured rat spinal cord tissues generated more neurospheres earlier than did the culturing of intact tissues, and these neurosphere cells were multipotent and bFGF-responsive. Immunohistochemical analysis showed that there existed many bFGF(+) cells after SCI, the number of which were almost 15 times greater than that in an intact spinal cord. Increased bFGF production after SCI might activate quiescent progenitor cells, and thus initiate their cell proliferation. Finally, SCI to the nestin-promoter green fluorescent protein (GFP) transgenic mice showed broad proliferation of progenitor cells that were induced in the injured spinal cord. The culturing of injured spinal cord tissues from these transgenic mice provides direct evidence that neurospheres can be generated by SCI-activated nestin(+) cells. Thus, the activation of bFGF-responsive progenitor cells and the concomitant increase in the population of bFGF(+) cells following SCI might be beneficial for spinal cord repair if these progenitor cells are properly manipulated. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Faber Canc Inst, Dept Neurobiol, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Neurobiol & Anat, Sakyo Ku, Kyoto 6068501, Japan. Univ Tokyo, Grad Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1130033, Japan. RP Xu, Y (reprint author), Harvard Univ, Sch Med, Dana Faber Canc Inst, Dept Canc Biol, 1 Jimmy Fund Way,SM 1020, Boston, MA 02115 USA. EM Yi_Xu@dfci.harvard.edu NR 26 TC 30 Z9 37 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 24 PY 2006 VL 397 IS 3 BP 174 EP 179 DI 10.1016/j.neulet.2005.12.051 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 027QW UT WOS:000236431300003 PM 16406666 ER PT J AU Jamieson, BD Ibarrondo, FJ Wong, JT Hausner, MA Ng, HL Fuerst, M Price, C Shih, R Elliott, J Hultin, PM Hultin, LE Anton, PA Yang, OO AF Jamieson, BD Ibarrondo, FJ Wong, JT Hausner, MA Ng, HL Fuerst, M Price, C Shih, R Elliott, J Hultin, PM Hultin, LE Anton, PA Yang, OO TI Transience of vaccine-induced HIV-1-specific CTL and definition of vaccine "response" SO VACCINE LA English DT Article DE HIV-1; vaccine; CTL ID T-CELL RESPONSES; IMMUNODEFICIENCY-VIRUS TYPE-1; LYMPHOCYTE RESPONSES; HIV-INFECTION; VIRAL LOAD; MACAQUES; IMMUNITY; SUPERINFECTION; VIREMIA; TRIALS AB Many vaccine approaches emphasize producing HIV-1-specific CD8(+) T-lymphocyte (CTL) responses. Towards this goal, many studies simply classify vaccinees as "responders" or "nonresponders," based on arbitrary cutoff criteria, HIV-1-uninfected participants receiving the TBC-3B vaccine were assessed for HIV-1-specific CTL by interferon-gamma ELISpot, and compared to HIV-1-infected control subjects not on antiretroviral therapy. Vaccinees also were tested for HIV-1-specific antibody responses and generalized CD8(+) T-lymphocyte activation. Different criteria for vaccine "responder" status were applied to the measured CTL values. The vaccinees showed evidence of vaccine exposure by CD8(+) T-lymphocyte activation and HIV-1-specific antibodies. Considering any single positive HIV-1-specific CTL measurement a vaccine "response," all vaccinees could be classified as "responders," but even slight increases in the stringency of response criteria resulted in a steep decline of the "response" rate. In contrast, HIV-1-infected persons were clearly "responders" against the same proteins by the same criteria. Quantitative assessment of CTL demonstrated low and transient HIV-1-specific CTL compared to natural infection. These analyses emphasize the pitfalls of summarizing vaccine study results using simple cutoff criteria to define response rates, and suggest the utility of more comprehensive descriptions to describe vaccine immunogenicity and persistence of responses. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, UCLA AIDS Inst, Div Infect Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Yang, OO (reprint author), Univ Calif Los Angeles, Med Ctr, UCLA AIDS Inst, Div Infect Dis, 37-121 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM oyang@mednet.ucla.edu FU NIAID NIH HHS [R01 AI/DK50467] NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 24 PY 2006 VL 24 IS 17 BP 3426 EP 3431 DI 10.1016/j.vaccine.2006.02.023 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 035MM UT WOS:000237005400004 PM 16545508 ER PT J AU Bernstein, BE Mikkelsen, TS Xie, XH Kamal, M Huebert, DJ Cuff, J Fry, B Meissner, A Wernig, M Plath, K Jaenisch, R Wagschal, A Feil, R Schreiber, SL Lander, ES AF Bernstein, BE Mikkelsen, TS Xie, XH Kamal, M Huebert, DJ Cuff, J Fry, B Meissner, A Wernig, M Plath, K Jaenisch, R Wagschal, A Feil, R Schreiber, SL Lander, ES TI A bivalent chromatin structure marks key developmental genes in embryonic stem cells SO CELL LA English DT Article ID POLYCOMB GROUP-COMPLEXES; HISTONE CODE; HUMAN GENOME; TRANSPOSABLE ELEMENTS; EPIGENETIC REGULATION; X-INACTIVATION; METHYLATION; MOUSE; BINDING; METHYLTRANSFERASE AB The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed "bivalent domains," consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. CNRS, Inst Genet Mol, UMR 5535, Montpellier, France. Univ Montpellier 2, Montpellier, France. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Bernstein, BE (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM bbernstein@partners.org RI Mikkelsen, Tarjei/A-1306-2007; Feil, Robert/D-2087-2013; OI Mikkelsen, Tarjei/0000-0002-8133-3135; Feil, Robert/0000-0002-5671-5860; Plath, Kathrin/0000-0001-7796-3372 FU NCI NIH HHS [CA84198]; NICHD NIH HHS [HD045022]; NIGMS NIH HHS [GM38627] NR 59 TC 2669 Z9 2740 U1 50 U2 296 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 21 PY 2006 VL 125 IS 2 BP 315 EP 326 DI 10.1016/j.cell.2006.02.041 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038RT UT WOS:000237241500021 PM 16630819 ER PT J AU Gesty-Palmer, D Chen, MY Reiter, E Ahn, S Nelson, CD Wang, ST Eckhardt, AE Cowan, CL Spurney, RF Luttrell, LM Lefkowitz, RJ AF Gesty-Palmer, D Chen, MY Reiter, E Ahn, S Nelson, CD Wang, ST Eckhardt, AE Cowan, CL Spurney, RF Luttrell, LM Lefkowitz, RJ TI Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASES; COUPLED RECEPTOR; INDEPENDENT FUNCTIONS; ADRENERGIC-RECEPTOR; KIDNEY-CELLS; PEPTIDE; PTH; BONE; DESENSITIZATION; INTERMITTENT AB Parathyroid hormone (PTH) regulates calcium homeostasis via the type I PTH/PTH-related peptide (PTH/PTHrP) receptor (PTH1R). The purpose of the present study was to identify the contributions of distinct signaling mechanisms to PTH-stimulated activation of the mitogen-activated protein kinases (MAPK) ERK1/2. In Human embryonic kidney 293 (HEK293) cells transiently transfected with hPTH1R, PTH stimulated a robust increase in ERK activity. The time course of ERK1/2 activation was biphasic with an early peak at 10 min and a later sustained ERK1/2 activation persisting for greater than 60 min. Pretreatment of HEK293 cells with the PKA inhibitor H89 or the PKC inhibitor GF109203X, individually or in combination reduced the early component of PTH-stimulated ERK activity. However, these inhibitors of second messenger dependent kinases had little effect on the later phase of PTH-stimulated ERK1/2 phosphorylation. This later phase of ERK1/2 activation at 30-60 min was blocked by depletion of cellular beta-arrestin 2 and beta-arrestin 1 by small interfering RNA. Furthermore, stimulation of hPTH1R with PTH analogues, [Trp(1)] PTHrp-(1-36) and [D-Trp(12), Tyr(34)] PTH-(7-34), selectively activated G(s)/PKA-mediated ERK1/2 activation or G protein-independent/beta-arrestin-dependent ERK1/2 activation, respectively. It is concluded that PTH stimulates ERK1/2 through several distinct signal transduction pathways: an early G protein-dependent pathway meditated by PKA and PKC and a late pathway independent of G proteins mediated through beta-arrestins. These findings imply the existence of distinct active conformations of the hPTH1R responsible for the two pathways, which can be stimulated by unique ligands. Such ligands may have distinct and valuable therapeutic properties. C1 Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Biochem, Durham, NC 27710 USA. Durham Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC 27705 USA. INRA, F-37380 Nouzilly, France. Xsira Pharmaceut, Morrisville, NC 27709 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Lefkowitz, RJ (reprint author), Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Med, Box 3821, Durham, NC 27710 USA. EM lefko001@receptor-biol.duke.edu FU NHLBI NIH HHS [HL16037, HL70631]; NICHD NIH HHS [HD043446]; NIDDK NIH HHS [DK64353] NR 47 TC 275 Z9 283 U1 2 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 2006 VL 281 IS 16 BP 10856 EP 10864 DI 10.1074/jbc.M513380200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200025 PM 16492667 ER PT J AU Salas, A Shimaoka, M Phan, U Kim, M Springer, TA AF Salas, A Shimaoka, M Phan, U Kim, M Springer, TA TI Transition from rolling to firm adhesion can be mimicked by extension of integrin alpha(L)beta(2) in an intermediate affinity state SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; I-LIKE DOMAIN; DISULFIDE BOND; CONFORMATION; REVEALS; LFA-1; FLOW; ALPHA-L-BETA-2; ADHESIVENESS; ANTAGONISTS AB alpha(L)beta(2) affinity for intercellular adhesion molecule-1 (ICAM-1) is regulated by the conformation of the alpha(L) I domain, which is in turn controlled by the conformation and orientation of other adjacent domains. Additionally, overall integrin conformation (bent versus straightened) influences the orientation of the I domain and access to its ligands, influencing adhesive efficiency. The open or high affinity I domain conformation supports strong adhesion, whereas the closed, low affinity conformation mediates weak interactions or rolling. We have previously suggested that alpha(L)beta(2) can also exist on the cell surface in an intermediate affinity state. Here we have studied the adhesive properties of integrin alpha(L)beta(2) containing mutant I domains with intermediate affinities for ICAM-1. In an overall bent conformation, the intermediate affinity state of alpha(L)beta(2) is hardly detected by conventional adhesion assays, but robust adhesion is seen when an extended conformation is induced by a small molecule alpha/beta I allo-steric antagonist. Intermediate affinity alpha(L)beta(2) supports more stable rolling than wild-type alpha(L)beta(2) under shear conditions. Moreover, antagonist-induced extension transforms rolling adhesion into firm adhesion in a manner reminiscent of chemokine activation of integrin alpha(L)beta(2). These findings suggest the relevance of intermediate affinity states of alpha(L)beta(2) to the transition between inactive and active states and demonstrate the importance of both I domain affinity and overall integrin conformation for cell adhesion. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu OI Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798] NR 25 TC 49 Z9 50 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 APR 21 PY 2006 VL 281 IS 16 BP 10876 EP 10882 DI 10.1074/jbc.M512472200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200027 PM 16505487 ER PT J AU Gurtan, AM Stuckert, P D'Andrea, AD AF Gurtan, AM Stuckert, P D'Andrea, AD TI The WD40 repeats of FANCL are required for Fanconi anemia core complex assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID E3 UBIQUITIN LIGASE; DNA-DAMAGE RESPONSE; NUCLEAR ACCUMULATION; PROTEINS FANCA; BRCA PATHWAY; RING DOMAIN; GENE; REVEALS; CHROMATIN; INTERACT AB Fanconi anemia (FA) is an autosomal recessive disorder characterized by aplastic anemia, cancer susceptibility, and cellular sensitivity to mitomycin C. Eight of the 11 cloned Fanconi anemia gene products (FANCA, -B, -C, -E, -F, -G, -L, and -M) form a multisubunit nuclear complex ( FA core complex) required for monoubiquitination of a downstream FA protein, FANCD2. FANCL, which possesses three WD40 repeats and a plant homeodomain (PHD), is the putative E3 ubiquitin ligase subunit of the FA complex. Here, we demonstrate that the WD40 repeats of FANCL are required for interaction with other subunits of the FA complex. The PHD is dispensable for this interaction, although it is required for FANCD2 mono-ubiquitination. The PHD of FANCL also shares sequence similarity to the canonical RING finger of c-CBL, including a conserved tryptophan required for E2 binding by c-CBL. Mutation of this tryptophan in the FANCL PHD significantly impairs in vivo mono-ubiquitination of FANCD2 and in vitro auto-ubiquitination activity, and partially impairs restoration of mitomycin C resistance. We propose a model in which FANCL, via its WD40 region, binds the FA complex and, via its PHD, recruits an as-yet-unidentified E2 for mono-ubiquitination of FANCD2. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Biol & Biomed Sci Program, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St,M640, Boston, MA 02115 USA. EM Alan_Dandrea@dfci.harvard.edu FU NHLBI NIH HHS [R01HL52725]; PHS HHS [R01KD43889] NR 49 TC 36 Z9 38 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 21 PY 2006 VL 281 IS 16 BP 10896 EP 10905 DI 10.1074/jbc.M511411200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033BV UT WOS:000236822200030 PM 16474167 ER PT J AU Indic, P Brown, EN AF Indic, P Brown, EN TI Characterizing the amplitude dynamics of the human core-temperature circadian rhythm using a stochastic-dynamic model SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE biological clock; amplitude dynamics; maximum likelihood ID CYCLE OSCILLATOR MODEL; LIGHT EXPOSURE; BRIGHT LIGHT; PACEMAKER; SLEEP; PHASE; MELATONIN; ENTRAINMENT; SUPPRESSION; RECOVERY AB Two measures, amplitude and phase, have been used to describe the characteristics of the endogenous human circadian pacemaker, a biological clock located in the hypothalamus. Although many studies of change in circadian phase with respect to different stimuli have been conducted, the physiologic implications of the amplitude changes (dynamics) of the pacemaker are unknown. It is known that phase changes of the human circadian pacemaker have a significant impact on sleep timing and content.. hormone secretion, subjective alertness and neurobehavioral performance. However, the changes in circadian amplitude with respect to different stimuli are less well documented. Although amplitude dynamics of the human circadian pacemaker are observed in physiological rhythms such as plasma cortisol, plasma melatonin and core temperature data, currently methods are not available to accurately characterize the amplitude dynamics from these rhythms. Of the three rhythms core temperature is the only reliable variable that can be monitored continuously in real time with a high sampling rate. To characterize the amplitude dynamics of the circadian pacemaker we propose a stochastic-dynamic model of core temperature data that contains both stochastic and dynamic characteristics. In this model the circadian component that has a dynamic characteristic is represented as a perturbation solution of the van der Pol equation and the thermoregulatory response in the data that has a stochastic characteristic is represented as a first-order autoregressive process. The model parameters are estimated using data with a maximum likelihood procedure and the goodness-of-fit measures along with the associated standard error of the estimated parameters provided inference about the amplitude dynamics of the pacemaker. Using this model we analysed core temperature data from an experiment designed to exhibit amplitude dynamics. We found that the circadian pacemaker recovers slowly to an equilibrium level following amplitude suppression. In humans this reaction to perturbation from equilibrium value has potential physiological implications. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Stat Res Lab,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. MIT, Boston, MA 02114 USA. RP Indic, P (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Premananda.Indic@umassmed.edu FU NIDA NIH HHS [DA015644]; NIMH NIH HHS [MH59733, MH61637] NR 45 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 21 PY 2006 VL 239 IS 4 BP 499 EP 506 DI 10.1016/j.jtbi.2005.08.015 PG 8 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 034SD UT WOS:000236950000010 PM 16223510 ER PT J AU Parodi, K Bortfeld, T AF Parodi, K Bortfeld, T TI A filtering approach based on Gaussian-powerlaw convolutions for local PET verification of proton radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; IN-BEAM PET; THERAPY; DISTRIBUTIONS; FEASIBILITY AB Because proton beams activate positron emitters in patients, positron emission tomography (PET) has the potential to play a unique role in the in vivo verification of proton radiotherapy. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution. Current treatment verification strategies using PET therefore compare the actual PET image with full-blown Monte Carlo simulations of the PET signal. In this paper, we describe a simpler and more direct way to reconstruct the expected PET signal from the local radiation dose distribution near the distal fall-off region, which is calculated by the treatment planning programme. Under reasonable assumptions, the PET image can be described as a convolution of the dose distribution with a filter function. We develop a formalism to derive the filter function analytically. The main concept is the introduction of '(Q) over tilde' functions defined as the convolution of a Gaussian with a powerlaw function. Special (Q) over tilde functions are the Gaussian itself and the error function. The convolution of two (Q) over tilde functions is another (Q) over tilde function. By fitting elementary dose distributions and their corresponding PET signals with (Q) over tilde functions, we derive the (Q) over tilde function approximation of the filter. The new filtering method has been validated through comparisons with Monte Carlo calculations and, in one case, with measured data. While the basic concept is developed under idealized conditions assuming that the absorbing medium is homogeneous near the distal fall-off region, a generalization to inhomogeneous situations is also described. As a result, the method can determine the distal fall-off region of the PET signal, and consequently the range of the proton beam, with millimetre accuracy. Quantification of the produced activity is possible. In conclusion, the PET activity resulting from a proton beam treatment can be determined by locally filtering the dose distribution as obtained from the treatment planning system. The filter function can be calculated analytically using convolutions of Gaussians and powerlaw functions. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Parodi, K (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM kparodi@partners.org; tbortfeld@partners.org FU NCI NIH HHS [5 P01 CA21239-25] NR 24 TC 45 Z9 46 U1 1 U2 5 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 APR 21 PY 2006 VL 51 IS 8 BP 1991 EP 2009 DI 10.1088/0031-9155/51/8/003 PG 19 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 045WS UT WOS:000237774000003 PM 16585841 ER PT J AU Meyerhardt, JA Zhu, AX Enzinger, PC Ryan, DP Clark, JW Kulke, MH Earle, CC Vincitore, M Michelini, A Sheehan, S Fuchs, CS AF Meyerhardt, JA Zhu, AX Enzinger, PC Ryan, DP Clark, JW Kulke, MH Earle, CC Vincitore, M Michelini, A Sheehan, S Fuchs, CS TI Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated patients with metastastic colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; 1ST-LINE TREATMENT; PLUS IRINOTECAN; THERAPY; LEUCOVORIN; TRIAL; FLUOROURACIL; CETUXIMAB; MALIGNANCIES; MULTICENTER AB Purpose To investigate the combination of erlotinib, capecitabine, and oxaliplatin in patients who were previously treated for metastatic colorectal cancer. Patients and Methods Patients were eligible if they had metastatic colorectal cancer that progressed, were intolerant to first-line chemotherapy, or had disease recurrence within 1 year of adjuvant therapy for early-stage disease. Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine at 1,000 mg/m(2) (reduced to 750 mg/m(2) after the first 13 patients) twice a day on days 1 to 14, and intravenous oxaliplatin at 130 mg/m(2) on day 1. Results Thirty-two patients were enrolled onto this phase II study. By intention-to-treat analyses, eight patients (25%) experienced a partial response and 14 patients (44%) had stable disease for at least 12 weeks. The median progression-free survival was 5.4 months and the median overall survival was 14.7 months. These results were essentially unchanged when limited to the cohort of patients (78%) who received prior irinotecan for metastatic colorectal cancer. Most common grade 3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%), dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced with a lower starting dose of capecitabine. Conclusion The combination of capecitabine, oxaliplatin, and erlotinib seems to have promising activity against metastatic colorectal cancer in patients who received prior chemotherapy, with a relatively higher response rate and progression-free survival compared with previous reports of either infusional FU, leucovorin, and oxaliplatin or capecitabine and oxaliplatin in similar patient populations. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM jmeyerhardt@partners.org NR 33 TC 67 Z9 69 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2006 VL 24 IS 12 BP 1892 EP 1897 DI 10.1200/JCO.2005.05.3728 PG 6 WC Oncology SC Oncology GA 037CM UT WOS:000237124300018 PM 16622264 ER PT J AU Zhu, AX Blaszkowsky, LS Ryan, DP Clark, JW Muzikansky, A Horgan, K Sheehan, S Hale, KE Enzinger, PC Bhargava, P Stuart, K AF Zhu, AX Blaszkowsky, LS Ryan, DP Clark, JW Muzikansky, A Horgan, K Sheehan, S Hale, KE Enzinger, PC Bhargava, P Stuart, K TI Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in patients with advanced hepatocellular carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROGNOSTIC-SIGNIFICANCE; UNITED-STATES; CANCER; THALIDOMIDE; TRIAL; GERCOR; ADENOCARCINOMA; CHEMOTHERAPY; DOXORUBICIN AB Purpose Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and Methods Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m(2) was administered as a dose rate infusion at 10 mg/m(2)/min followed by oxaliplatin at 85 mg/m(2) on days 2 and 16. Results Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. Conclusion GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation. C1 Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhu, AX (reprint author), Massachusetts Gen Hosp, Ctr Canc, Tucker Gosnell Ctr Gastrointestinal Canc, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM azhu@partners.org NR 35 TC 258 Z9 283 U1 3 U2 6 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 APR 20 PY 2006 VL 24 IS 12 BP 1898 EP 1903 DI 10.1200/JCO.2005.04.9130 PG 6 WC Oncology SC Oncology GA 037CM UT WOS:000237124300019 PM 16622265 ER PT J AU Cigler, T Goss, PE AF Cigler, T Goss, PE TI Aromatase inhibitor withdrawal response in metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ESTRADIOL HYPERSENSITIVITY; ESTROGEN DEPRIVATION; TAMOXIFEN WITHDRAWAL; CELLS; THERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cigler, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2006 VL 24 IS 12 BP 1955 EP 1956 DI 10.1200/JCO.2005.03.4108 PG 2 WC Oncology SC Oncology GA 037CM UT WOS:000237124300029 PM 16622274 ER PT J AU Kwan, KY Allchorne, AJ Vollrath, MA Christensen, AP Zhang, DS Woolf, CJ Corey, DP AF Kwan, KY Allchorne, AJ Vollrath, MA Christensen, AP Zhang, DS Woolf, CJ Corey, DP TI TRPA1 contributes to cold, mechanical, and chemical Nociception but is not essential for hair-cell transduction SO NEURON LA English DT Article ID PRIMARY SENSORY NEURONS; SPARED NERVE INJURY; ION-CHANNEL TRPA1; NEUROPATHIC PAIN; THERMOTRP CHANNELS; SEX-DIFFERENCES; TRK RECEPTORS; GROWTH-FACTOR; TIP LINKS; RAT AB TRPA1, a member of the transient receptor potential (TRP) family of ion channels, is expressed by dorsal root ganglion neurons and by cells of the inner ear, where it has proposed roles in sensing sound, painful cold, and irritating chemicals. To test the in vivo roles of TRPA1, we generated a mouse in which the essential exons required for proper function of the Trpa1 gene were deleted. Knockout mice display behavioral deficits in response to mustard oil, to cold (similar to 0 degrees C), and to punctate mechanical stimuli. These mice have a normal startle reflex to loud noise, a normal sense of balance, a normal auditory brainstem response, and normal transduction currents in vestibular hair cells. TRPA1 is apparently not essential for hair-cell transduction but contributes to the transduction of mechanical, cold, and chemical stimuli in nociceptor sensory neurons. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Kwan, KY (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM kelvin_kwan@hms.harvard.edu OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC-00304]; NINDS NIH HHS [NS-038253, NS-039518] NR 49 TC 675 Z9 700 U1 3 U2 47 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 20 PY 2006 VL 50 IS 2 BP 277 EP 289 DI 10.1016/j.neuron.2006.03.042 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 037VW UT WOS:000237176700014 PM 16630838 ER PT J AU Steinberg, KP Hudson, LD Goodman, RB Hough, CL Lanken, PN Hyzy, R Thompson, BT Ancukiewicz, M AF Steinberg, KP Hudson, LD Goodman, RB Hough, CL Lanken, PN Hyzy, R Thompson, BT Ancukiewicz, M CA Natl Heart Lung Blood Inst Acute R TI Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HIGH-DOSE METHYLPREDNISOLONE; CRITICALLY-ILL PATIENTS; SEPTIC SHOCK; SEVERE SEPSIS; CLINICAL-TRIAL; LUNG INJURY; THERAPY; ARDS; MORTALITY; HYDROCORTISONE AB BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS. METHODs: We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness. CONCLUSIONS: These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. C1 Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Steinberg, KP (reprint author), Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Box 359762,325 9th Ave, Seattle, WA 98104 USA. EM steinkp@u.washington.edu NR 38 TC 497 Z9 547 U1 3 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 20 PY 2006 VL 354 IS 16 BP 1671 EP 1684 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 033ZP UT WOS:000236893900004 PM 16625008 ER PT J AU Gibbons, FK Branda, JA Shepard, JO Howell, MD Hales, CA Harris, NL AF Gibbons, FK Branda, JA Shepard, JO Howell, MD Hales, CA Harris, NL TI Case 12-2006: A 37-year-old man with hemoptysis and a pulmonary infiltrate - Tuberculosis, primary, pulmonary. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LUNG FIELD TUBERCULOSIS; RADIOLOGIC MANIFESTATIONS; CT; FLUOROQUINOLONES; RESISTANCE; LYMPHOMA C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Gibbons, FK (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RI Howell, Michael/B-8065-2009 OI Howell, Michael/0000-0001-7003-6971 NR 37 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 20 PY 2006 VL 354 IS 16 BP 1729 EP 1737 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 033ZP UT WOS:000236893900011 PM 16625012 ER PT J AU Jones, L Goldstein, DR Hughes, G Strand, AD Collin, F Dunnett, SB Kooperberg, C Aragaki, A Olson, JM Augood, SJ Faull, RLM Luthi-Carter, R Moskvina, V Hodges, AK AF Jones, Lesley Goldstein, Darlene R. Hughes, Gareth Strand, Andrew D. Collin, Francois Dunnett, Stephen B. Kooperberg, Charles Aragaki, Aaron Olson, James M. Augood, Sarah J. Faull, Richard L. M. Luthi-Carter, Ruth Moskvina, Valentina Hodges, Angela K. TI Assessment of the relationship between pre-chip and post-chip quality measures for Affymetrix GeneChip expression data SO BMC BIOINFORMATICS LA English DT Article ID POSTMORTEM HUMAN BRAIN; PROBE LEVEL; MICROARRAY; TISSUE AB Background: Gene expression microarray experiments are expensive to conduct and guidelines for acceptable quality control at intermediate steps before and after the samples are hybridised to chips are vague. We conducted an experiment hybridising RNA from human brain to 117 U133A Affymetrix GeneChips and used these data to explore the relationship between 4 pre-chip variables and 22 post-chip outcomes and quality control measures. Results: We found that the pre-chip variables were significantly correlated with each other but that this correlation was strongest between measures of RNA quality and cRNA yield. Post-mortem interval was negatively correlated with these variables. Four principal components, reflecting array outliers, array adjustment, hybridisation noise and RNA integrity, explain about 75% of the total post-chip measure variability. Two significant canonical correlations existed between the pre-chip and post-chip variables, derived from MAS 5.0, dChip and the Bioconductor packages affy and affyPLM. The strongest (CANCOR 0.838, p < 0.0001) correlated RNA integrity and yield with post chip quality control (QC) measures indexing 3 '/5 ' RNA ratios, bias or scaling of the chip and scaling of the variability of the signal across the chip. Post-mortem interval was relatively unimportant. We also found that the RNA integrity number (RIN) could be moderately well predicted by post- chip measures B_ACTIN35, GAPDH35 and SF. Conclusion: We have found that the post- chip variables having the strongest association with quantities measurable before hybridisation are those reflecting RNA integrity. Other aspects of quality, such as noise measures (reflecting the execution of the assay) or measures reflecting data quality (outlier status and array adjustment variables) are not well predicted by the variables we were able to determine ahead of time. There could be other variables measurable pre-hybridisation which may be better associated with expression data quality measures. Uncovering such connections could create savings on costly microarray experiments by eliminating poor samples before hybridisation. C1 Univ Cardiff Wales, Dept Med Psychol, Sch Med, Cardiff, Wales. Univ Cardiff Wales, Dept Med Genet, Sch Med, Cardiff, Wales. Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA. Univ Cardiff Wales, Sch Biosci, Cardiff, Wales. Massachusetts Gen Hosp, MIND, Charlestown, MA 02129 USA. Univ Auckland, Auckland City Hosp, Dept Anat Radiol, Auckland 1, New Zealand. RP Jones, L (reprint author), Univ Cardiff Wales, Dept Med Psychol, Sch Med, Cardiff, Wales. EM jonesl1@cf.ac.uk; Darlene.Goldstein@epfl.ch; hughesgp@cf.ac.uk; astrand@fhcrc.org; Francois_Collin@affymetrix.com; dunnettsb@cf.ac.uk; clk@fhcrc.org; aaragaki@WHI.org; jolson@fhcrc.org; augood@helix.mgh.harvard.edu; rlm.faull@auckland.ac.nz; ruth.luthi-carter@epfl.ch; moskvinav1@cf.ac.uk; Angela.Hodges@iop.kcl.ac.uk RI Dunnett, Stephen/A-5869-2010; Hodges, Angela/C-5676-2011; OI Dunnett, Stephen/0000-0003-1826-1578; Escott-Price, Valentina/0000-0003-1784-5483 FU Medical Research Council [G0500794]; NCI NIH HHS [R01 CA074841, R29 CA074841, CA 74841] NR 27 TC 27 Z9 30 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 19 PY 2006 VL 7 AR 211 DI 10.1186/1471-2105-7-211 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 070IZ UT WOS:000239516600001 PM 16623940 ER PT J AU Bellinger, DC Trachtenberg, F Barregard, L Tavares, M Cernichiari, E Daniel, D McKinlay, S AF Bellinger, DC Trachtenberg, F Barregard, L Tavares, M Cernichiari, E Daniel, D McKinlay, S TI Neuropsychological and renal effects of dental amalgam in children - A randomized clinical trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MERCURY CONCENTRATIONS; 6-YEAR-OLD CHILDREN; EXPOSURE; HEALTH; LEAD; FILLINGS; URINE; INTELLIGENCE; DISEASE; BLOOD AB Context No randomized trials have been published that address the concern that inhalation of mercury vapor released by amalgam dental restorations causes adverse health effects. Objective To compare the neuropsychological and renal function of children whose dental caries were restored using amalgam or mercury-free materials. Design and Setting The New England Children's Amalgam Trial was a 2-group randomized safety trial involving 5 community health dental clinics in Boston, Mass, and 1 in Farmington, Me, between September 1997 and March 2005. Participants and Intervention A total of 534 children aged 6 to 10 years at baseline with no prior amalgam restorations and 2 or more posterior teeth with caries were randomly assigned to receive dental restoration of baseline and incident caries during a 5-year follow-up period using either amalgam ( n= 267) or resin composite ( n = 267) materials. Main Outcome Measures The primary neuropsychological outcome was 5-year change in full-scale IQ scores. Secondary outcomes included tests of memory and visuomotor ability. Renal glomerular function was measured by creatinine-adjusted albumin in urine. Results Children had a mean of 15 tooth surfaces ( median, 14) restored during the 5-year period ( range, 0-55). Assignment to the amalgam group was associated with a significantly higher mean urinary mercury level (0.9 vs 0.6 mu g/g of creatinine at year 5, P <. 001). After adjusting for randomization stratum and other covariates, no statistically significant differences were found between children in the amalgam and composite groups in 5-year change in full-scale IQ score (3.1 vs 2.1, P=. 21). The difference in treatment group change scores was 1.0 (95% confidence interval, - 0.6 to 2.5) full-scale IQ score point. No statistically significant differences were found for 4-year change in the general memory index (8.1 vs 7.2, P=. 34), 4-year change in visuomotor composite (3.8 vs 3.7, P=. 93), or year 5 urinary albumin ( median, 7.5 vs 7.4 mg/g of creatinine, P=. 61). Conclusions In this study, there were no statistically significant differences in adverse neuropsychological or renal effects observed over the 5-year period in children whose caries were restored using dental amalgam or composite materials. Although it is possible that very small IQ effects cannot be ruled out, these findings suggest that the health effects of amalgam restorations in children need not be the basis of treatment decisions when choosing restorative dental materials. C1 New England Res Inst Inc, Watertown, MA 02472 USA. Childrens Hosp Boston, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Gothenburg Univ, Sahlgrenska Univ Hosp & Acad, Dept Occupat & Environm Med, Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. Univ Rochester, Sch Med, Dept Environm Med, Rochester, NY USA. Univ Maine, Dept Psychol, Farmington, CT USA. RP McKinlay, S (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM smckinlay@neriscience.com FU NIDCR NIH HHS [U01 DE11886] NR 35 TC 136 Z9 138 U1 2 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 2006 VL 295 IS 15 BP 1775 EP 1783 DI 10.1001/jama.295.15.1775 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 033XG UT WOS:000236886900020 PM 16622139 ER PT J AU Yan, LJL Liu, K Daviglus, ML Colangelo, LA Kiefe, CI Sidney, S Matthews, KA Greenland, P AF Yan, LJL Liu, K Daviglus, ML Colangelo, LA Kiefe, CI Sidney, S Matthews, KA Greenland, P TI Education, 15-year risk factor progression, and coronary artery calcium in young adulthood and early middle age - The Coronary Artery Risk Development in Young Adults study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AMERICAN-HEART-ASSOCIATION; INTIMA-MEDIA THICKNESS; ALL-CAUSE MORTALITY; OF-THE-LITERATURE; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; CAROTID ATHEROSCLEROSIS; SUBCLINICAL ATHEROSCLEROSIS; POSTMENOPAUSAL WOMEN; COMPUTED-TOMOGRAPHY AB Context The inverse association between education and cardiovascular disease is well established, but little is known about the relationship between education and subclinical disease, which is free from medical access and treatment-related influences, or about possible mediating pathways for these relationships. Objective To examine the association of education with coronary artery calcium (CAC), an indicator of subclinical atherosclerosis, and cardiovascular risk factors, and their changes as potential mediators. Design, Setting, and Participants A population-based, prospective, observational study ( Coronary Artery Risk Development in Young Adults [ CARDIA]) of 2913 eligible participants (44.9% black; 53.9% women) recruited from 4 metropolitan areas ( Birmingham, Ala; Chicago, Ill; Minneapolis, Minn; and Oakland, Calif) in both the baseline (1985-1986, ages 18-30 years) and year 15 examinations (2000-2001, ages 33-45 years). Education ( year 15) was classified into less than high school (n= 128), high school graduate ( n= 498), some college ( n= 902), college graduate ( n= 764), and more than college ( n= 621). Main Outcome Measure Presence of CAC, measured twice by computed tomography ( mean total Agatston score > 0) at year 15. Results Overall CAC prevalence in this sample was 9.3%. After adjusting for age, race, and sex, the odds ratios (ORs) for having CAC were 4.14 (95% confidence interval [CI], 2.33- 7.35) for less than high school education, 1.89 ( 95% CI, 1.23- 2.91) for high school graduate, 1.47 ( 95% CI, 0.99-2.19) for some college, and 1.24 ( 95% CI, 0.84-1.85) for college graduate compared with those participants with more than a college education ( P for trend <. 001). This was also consistent within each of the 4 race-sex groups. Adjustment for baseline systolic blood pressure, smoking, waist circumference, physical activity, and total cholesterol reduced the ORs to 2.61 ( 95% CI, 1.40-4.85) for less than high school, 1.38 ( 95% CI, 0.88-2.17) for high school graduate, 1.17 ( 95% CI, 0.78-1.77) for some college, and 1.13 ( 95% CI, 0.76-1.69) for college graduate compared with more than a college education ( P for trend=. 01), and only slightly attenuated by further adjustment for 15-year changes in risk factors. Conclusion Education was inversely associated with the prevalence of CAC, an association partially explained by baseline risk factors and minimally by 15-year changes in risk factors. C1 Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. Peking Univ, Dept Hlth Econ & Management, Guanghua Sch Management, Beijing 100871, Peoples R China. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Yan, LJL (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM lijing@northwestern.edu FU NHLBI NIH HHS [N01-HC-48049, N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48050] NR 51 TC 54 Z9 58 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 2006 VL 295 IS 15 BP 1793 EP 1800 DI 10.1001/jama.295.15.1793 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 033XG UT WOS:000236886900022 PM 16622141 ER PT J AU Kesselheim, AS Ferris, TG Studdert, DM AF Kesselheim, AS Ferris, TG Studdert, DM TI Will physician-level measures of clinical performance be used in medical malpractice litigation? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARDIAC-SURGERY; JURORS; CARE C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners MGH Inst Hlth Policy, Div Gen Med, Boston, MA 02114 USA. RP Studdert, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM studdert@hsph.harvard.edu NR 24 TC 13 Z9 13 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 2006 VL 295 IS 15 BP 1831 EP 1834 DI 10.1001/jama.295.15.1831 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 033XG UT WOS:000236886900026 PM 16622145 ER PT J AU Max, MB Wu, TX Atlas, SJ Edwards, RR Haythornthwaite, JA Bollettino, AF Hipp, HS McKnight, CD Osman, IA Crawford, EN Pao, M Nejim, J Kingman, A Aisen, DC Scully, MA Keller, RB Goldman, D Belfer, I AF Max, Mitchell B. Wu, Tianxia Atlas, Steven J. Edwards, Robert R. Haythornthwaite, Jennifer A. Bollettino, Antonella F. Hipp, Heather S. McKnight, Colin D. Osman, Inge A. Crawford, Erin N. Pao, Maryland Nejim, Jemiel Kingman, Albert Aisen, Daniel C. Scully, Michele A. Keller, Robert B. Goldman, David Belfer, Inna TI A clinical genetic method to identify mechanisms by which pain causes depression and anxiety SO MOLECULAR PAIN LA English DT Article ID MAINE LUMBAR SPINE; RISK-FACTORS; NONSURGICAL MANAGEMENT; PSYCHIATRIC-DISORDERS; PERSISTENT PAIN; DISC HERNIATION; RECEPTOR GENE; PRIMARY-CARE; BACK-PAIN; POLYMORPHISM AB Background: Pain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between ( 1) the amount of surgical pain relief, and ( 2) the alleles of the gene, on depression and anxiety during the first postoperative year. Results: We collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced > 25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood - the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin- 2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery. Conclusion: Genomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts. C1 Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Div Intramural Res, NIH,DHHS, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Stat Core, Div Populat & Hlth Promot Sci, NIH,DHHS, Bethesda, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Gen Med Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Clin Epidemiol Unit, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. NIMH, Off Clin Director, NIH, DHHS, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, DHHS, Rockville, MD 20852 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. Maine Spine & Rehabil, Portland, ME USA. RP Max, MB (reprint author), Natl Inst Dent & Craniofacial Res, Clin Pain Res Sect, Div Intramural Res, NIH,DHHS, Bethesda, MD USA. EM mm77k@nih.gov; wuti@mail.nih.gov; satlas@partners.org; redwar10@jhmi.edu; jhayth1@jhmi.edu; bollettinoa@nidcr.nih.gov; hs_hipp@yahoo.com; mcknightc@ohsu.edu; osmani@mail.nih.gov; crawforde@mail.nih.gov; paom@mail.nih.gov; nejimj@mail.nih.gov; kingmana@mail.nih.gov; chicken1@gmail.com; mascully7@aol.com; rbkeller@wildblue.net; dgneuro@mail.nih.gov; ibelfer@mail.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU AHRQ HHS [HS-09804, HS-06344, HS-08194, R01 HS009804]; Intramural NIH HHS; NIAAA NIH HHS [Z01 AA000301]; NIAMS NIH HHS [K23 AR051315, P60 AR048094]; NIDCR NIH HHS [Z01 DE000366]; NINDS NIH HHS [K24 NS002225, K24 NS02225] NR 50 TC 36 Z9 39 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD APR 19 PY 2006 VL 2 AR 14 DI 10.1186/1744-8069-2-14 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 165AV UT WOS:000246277100001 PM 16623937 ER PT J AU Smith-Bindman, R Miglioretti, DL Lurie, N Abraham, L Barbash, RB Strzelczyk, J Dignan, M Barlow, WE Beasley, CM Kerlikowske, K AF Smith-Bindman, R Miglioretti, DL Lurie, N Abraham, L Barbash, RB Strzelczyk, J Dignan, M Barlow, WE Beasley, CM Kerlikowske, K TI Does utilization of screening mammography explain racial and ethnic differences in breast cancer? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID WHITE WOMEN; BLACK-WOMEN; SOCIOECONOMIC-FACTORS; CARCINOMA SURVIVAL; AMERICAN WOMEN; UNITED-STATES; RACE; DIAGNOSIS; STAGE; DISPARITIES AB Background: Reasons for persistent differences in breast cancer mortality rates among various racial and ethnic groups have been difficult to ascertain. Objective: To determine reasons for disparities in breast cancer outcomes across racial and ethnic groups. Design: Prospective cohort. Setting: The authors pooled data from 7 mammography registries that participate in the National Cancer Institute-funded'Breast Cancer Surveillance Consortium. Cancer diagnoses were ascertained through linkage with pathology databases; Surveillance, Epidemiology, and End Results programs; and state tumor registries. Participants: 1010515 women 40 years of age and older who had at least 1 mammogram between 1996 and 2002; 17558 of these women had diagnosed breast cancer. Measurements: Patterns of mammography and the probability of inadequate mammography screening were examined. The authors evaluated whether overall and advanced cancer rates were similar across racial and ethnic groups and whether these rates were affected by the use of mammography. Results: African-American, Hispanic, Asian, and Native American women were more likely than white women to have received inadequate mammographic screening (relative risk, 1.2 [95% Cl, 1.2 to 1.2], 1.3 [Cl, 1.2 to 1.3], 1.4 [Cl, 1.3 to 1.4], and 1.2 [Cl, 1.1 to 1.2) respectively). African-American women were more likely than white, Asian, and Native American women to have large, advanced-stage, high-grade, and lymph node-positive tumors of the breast. The observed differences in advanced cancer rates between African American and white women were attenuated or eliminated after the cohort was stratified by screening history. Among women who were previously screened at intervals of 4 to 41 months, African -American women were no more likely to have large, advanced-stage tumors or lymph node involvement than white women with the same screening history. African-American women had higher rates of high-grade tumors than white women regardless of screening history. The lower rates of advanced cancer among Asian and Native American women persisted when the cohort was stratified by mammography history. Limitations: Results are based on a cohort of women who had received mammographic evaluations. Conclusions: African-American women are less likely to receive adequate mammographic screening than white women, which may explain the higher prevalence of advanced breast tumors among African-American women. Tumor characteristics may also contribute to differences in cancer outcomes because African-American women have higher-grade tumors than white women regardless of screening. These results suggest that adherence to recommended mammography screening intervals may reduce breast cancer mortality rates. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94115 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. RAND Corp, Arlington, VA USA. NCI, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Kentucky, Prevent Res Ctr, Lexington, KY USA. Canc Res & Biostat, Seattle, WA USA. Univ N Carolina, Pembroke, NC USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, 1600 Divisadero St, San Francisco, CA 94115 USA. EM Rebecca.Smith-Bindman@Radiology.UCSF.edu FU NCI NIH HHS [U01CA69976, U01CA70013, U01CA86082, U01CA63740, U01CA63736, U01CA63731, U01CA86076, U01CA70040, K07 CA86032] NR 49 TC 181 Z9 185 U1 2 U2 5 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 APR 18 PY 2006 VL 144 IS 8 BP 541 EP 553 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 035QZ UT WOS:000237017900001 PM 16618951 ER PT J AU Smetana, GW Lawrence, VA Cornell, JE AF Smetana, GW Lawrence, VA Cornell, JE TI Preoperative pulmonary risk stratification for noncardiothoracic surgery: Systematic review for the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID UPPER ABDOMINAL-SURGERY; MAJOR NONCARDIAC SURGERY; EARLY POSTOPERATIVE COMPLICATIONS; THORACOABDOMINAL AORTIC-ANEURYSM; COLORECTAL-CANCER SURGERY; HIP FRACTURE REPAIR; SURGICAL-PATIENTS; PERIOPERATIVE COMPLICATIONS; BLOOD-TRANSFUSION; VASCULAR-SURGERY AB Background: The importance of clinical risk factors for postoperative pulmonary complications and the value of preoperative testing to stratify risk are the subject of debate. Purpose: To systematically review the literature on preoperative pulmonary risk stratification before noncardiothoracic surgery. Data Sources: MEDLINE search from 1 January 1980 through 30 June 2005 and hand search of the bibliographies of retrieved articles. Study Selection: English -language studies that reported the effect of patient- and procedure- related risk factors and laboratory predictors on postoperative pulmonary complication rates after noncardiothoracic surgery and that met predefined inclusion criteria. Data Extraction: The authors used standardized abstraction instruments to extract data on study characteristics, hierarchy of research design, study quality, risk factors, and laboratory predictors. Data Synthesis: The authors determined random-effects pooled estimate odds ratios and, when appropriate, trim-and-fill estimates for patient- and procedure- related risk factors from studies that used multivatiable analyses. They assigned summary strength of evidence scores for each factor. Good evidence supports patient-related risk factors for postoperative pulmonary complications, including advanced age, American Society of Anesthesiologists class 2 or higher, functional dependence, chronic obstructive pulmonary disease, and congestive heart failure. Good evidence supports procedure-related risk factors for postoperative pulmonary complications, including aortic aneurysm repair, nonresective thoracic surgery, abdominal surgery, neurosurgery, emergency surgery, general anesthesia, head and neck surgery, vascular surgery, and prolonged surgery. Among laboratory predictors, good evidence exists only for serum albumin level less than 30 g/L. Insufficient evidence supports preoperative spirometry as a tool to stratify risk. Limitations: For certain risk factors and laboratory predictors, the literature provides only unadjusted estimates of risk. Prescreening, variable selection algorithms, and publication bias limited reporting of risk factors among studies using multivariable analysis. Conclusions: Selected clinical and laboratory factors allow risk stratification for postoperative pulmonary complications after noncardiothoracic surgery. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Sch Med, Boston, MA 02215 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Smetana, GW (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Sch Med, 330 Brookline Ave, Boston, MA 02215 USA. EM gsmetana@bidmc.harvard.edu NR 152 TC 240 Z9 263 U1 3 U2 9 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 APR 18 PY 2006 VL 144 IS 8 BP 581 EP 595 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 035QZ UT WOS:000237017900006 PM 16618956 ER PT J AU Lawrence, VA Cornell, JE Smetana, GW AF Lawrence, VA Cornell, JE Smetana, GW TI Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: Systematic review for the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID MAJOR ABDOMINAL-SURGERY; RANDOMIZED CONTROLLED TRIAL; PARENTERAL-NUTRITION; EPIDURAL-ANESTHESIA; INCENTIVE SPIROMETRY; OPEN CHOLECYSTECTOMY; AORTIC-SURGERY; CLINICAL-TRIAL; NASOGASTRIC DECOMPRESSION; GASTROINTESTINAL CANCER AB Background: Postoperative pulmonary complications are as frequent and clinically important as cardiac complications in terms of morbidity, mortality, and length of stay. However, there has been much less research and no previous systematic reviews of the evidence of interventions to prevent pulmonary complications. Purpose: To systematically review the literature on interventions to prevent postoperative pulmonary complications after noncardiothoracic surgery. Data Sources: MEDLINE English -language literature search, 1 January 1980 through 30 June 2005, plus bibliographies of retrieved publications. Study Selection: Randomized, controlled trials (RCTs); systematic reviews; or meta-analyses that met predefined inclusion criteria. Data Extraction: Using standardized forms, the authors abstracted data on study methods, quality, intervention and control groups, patient characteristics, surgery, postoperative pulmonary complications, and adverse events. Data Synthesis: The authors qualitatively synthesized, without meta-analysis, evidence from eligible studies. Good evidence (2 systematic reviews, 5 additional RCTs) indicates that lung expansion interventions (for example, incentive spirometry, deep breathing exercises, and continuous positive airway pressure) reduce pulmonary risk. Fair evidence suggests that selective, rather than routine, use of nasogastric tubes after abdominal surgery (2 meta-analyses) and short-acting rather than long-acting intraciperative neuromuscular blocking agents (1 RCT) reduce risk. The evidence is conflicting or insufficient for preoperative smoking cessation (1 RCT), epidural anesthesia (2 meta-analyses), epidural analgesia (6 RCTs, 1 meta-analysis), and laparoscopic (vs. open) operations (1 systematic review, 1 meta-analysis, 2 additional RCTs), although laparoscopic operations reduce pain and pulmonary compromise as measured by spirometry. While malnutrition is associated with increased pulmonary risk, routine total enteral or parenteral nutrition does not reduce risk (1 meta-analysis, 3 additional RCTs). Enteral formulations designed to improve immune status (immunonutrition) may prevent postoperative pneumonia (1 meta-analysis, 1 additional RCT). Limitations: The overall quality of the literature was fair: Ten of 20 RCTs and 6 of 11 systematic reviews were good quality. Conclusions: Few interventions have been shown to clearly or possibly reduce postoperative pulmonary complications. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Lawrence, VA (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr,Mail Code 7879, San Antonio, TX 78229 USA. EM vlawrence@uthscsa.edu NR 69 TC 169 Z9 182 U1 1 U2 22 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 APR 18 PY 2006 VL 144 IS 8 BP 596 EP 608 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 035QZ UT WOS:000237017900007 PM 16618957 ER PT J AU Cesario, DA Dec, GW AF Cesario, DA Dec, GW TI Implantable cardioverter-defibrillator therapy in clinical practice SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LONG-QT-SYNDROME; RIGHT-VENTRICULAR CARDIOMYOPATHY; CHRONIC HEART-FAILURE; SUDDEN CARDIAC DEATH; NONISCHEMIC DILATED CARDIOMYOPATHY; BUNDLE-BRANCH BLOCK; INTRAVENTRICULAR-CONDUCTION DELAY; ST-SEGMENT ELEVATION; MYOSIN HEAVY-CHAIN; HIGH-RISK PATIENTS AB Pharmacologic treatment of heart failure has led to dramatic improvements in survival and quality of life. Nonetheless, heart failure often progresses despite treatment with diuretics, angiotensin-converting enzyme inhibitors, beta-adrenergic blockers, aldosterone antagonists, and digoxin. Further, despite a steady decline in the risk of death from pump failure, many patients remain at high risk for sudden cardiac death. The annual incidence of sudden cardiac death in the U.S. alone has been estimated at 184,000 to over 400,000 cases. During the past decade, substantial advances have been made in the use of device-based therapy for this population. The role of the implantable cardioverter-defibrillator (ICD) continues to evolve in routine heart failure management. The current status of ICD therapy in the treatment of heart failure patients based on randomized clinical trial results and published practice guidelines is summarized in this review. C1 Massachusetts Gen Hosp, Div Cardiol, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. Univ Calif Irvine, Irvine, CA USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Heart Failure & Transplantat Unit, Bigelow 800,Mailstop 817,55 Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 79 TC 18 Z9 21 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 APR 18 PY 2006 VL 47 IS 8 BP 1507 EP 1517 DI 10.1016/j.jacc.2005.09.077 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033AR UT WOS:000236819000001 PM 16630984 ER PT J AU Rodriguez, AE Granada, JF Rodriguez-Alemparte, M Vigo, CF Delgado, J Fernandez-Pereira, C Pocovi, A Rodriguez-Granillo, AM Schulz, D Raizner, AE Palacios, I O'Neill, W Kaluza, GL Stone, G AF Rodriguez, AE Granada, JF Rodriguez-Alemparte, M Vigo, CF Delgado, J Fernandez-Pereira, C Pocovi, A Rodriguez-Granillo, AM Schulz, D Raizner, AE Palacios, I O'Neill, W Kaluza, GL Stone, G CA ORAR II Investigators TI Oral rapamycin after coronary bare-metal stent implantation to prevent restenosis - The prospective, randomized oral rapamycin in Argentina (ORAR II) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SIROLIMUS-ELUTING STENTS; DE-NOVO LESIONS; BALLOON ANGIOPLASTY; LUMINAL DIAMETER; ARTERY-DISEASE; DOUBLE-BLIND; INTRAVASCULAR ULTRASOUND; CONTROLLED-TRIAL; SLOW-RELEASE; FOLLOW-UP AB OBJECTIVES The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. BACKGROUND Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. METHODS Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. RESULTS Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively, 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 6.018). CONCLUSIONS This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis. C1 Otamendi Hosp, RA-1024 Buenos Aires, DF, Argentina. Methodist Hosp, Res Inst, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Columbia Univ, New York, NY USA. RP Rodriguez, AE (reprint author), Otamendi Hosp, Callao 1441 4 B, RA-1024 Buenos Aires, DF, Argentina. EM rodrigueza@sanatorio-otamendi.com.ar NR 33 TC 66 Z9 67 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 APR 18 PY 2006 VL 47 IS 8 BP 1522 EP 1529 DI 10.1016/j.jacc.2005.12.052 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033AR UT WOS:000236819000003 PM 16630986 ER PT J AU Wiviott, SD Morrow, DA Frederick, PD Antman, EM Braunwald, E AF Wiviott, SD Morrow, DA Frederick, PD Antman, EM Braunwald, E TI Application of the thrombolysis in myocardial infarction risk index in non-ST-segment elevation myocardial infarction - Evaluation of patients in the National Registry of Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; COOPERATIVE CARDIOVASCULAR PROJECT; INTRAVENOUS NPA; HEART SURVEY; SHORT-TERM; INTIME-II; MORTALITY; STRATIFICATION; OUTCOMES; SCORE AB OBJECTIVES The purpose of this research was to evaluate the Thrombolysis In Myocardial Infarction risk index (TRI) to characterize the risk of death among patients with non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND The TRI, calculated from baseline age, systolic pressure, and heart rate, was established in patients with ST-segment elevation myocardial infarction (STEMI) and is predictive of mortality. Patients presenting with NSTEMI are increasing compared to STEMI and constitute a group with varied risk. METHODS The TRI was calculated in 337,192 patients from the National Registry of Myocardial Infarction with NSTEML Values and outcomes were compared with 153,486 patients with STEMI classified by reperfusion status. Comparisons of baseline characteristics and clinical outcomes stratified by TRI were made. RESULTS There was a graded relationship between the TRI and mortality in patients with NSTEMI with a > 30-fold difference in mortality rates between lowest and highest deciles (p < 0.0001). The index showed good discrimination (c = 0.73). Overall mortality in the group with NSTEMI was higher (10.9%) than patients with STEMI treated with (6.6%) but lower than for STEMI patients not receiving reperfusion therapy (18.7%). The higher risk in comparison to patients with STEMI treated with reperfusion therapy was explained largely by the higher-risk profile of the population with NSTEMI. CONCLUSIONS There is a graded relationship between TRI and mortality in patients with NSTEMI. This simple risk index provides important information about mortality in patients across the spectrum of myocardial infarction, STEMI and NSTEMI. Early identification of NSTEMI patients who are at high risk of in-hospital mortality may provide clinicians with important information for initial triage and treatment. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Ovat Res Grp, Seattle, WA USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM swiviott@partners.org NR 24 TC 28 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 18 PY 2006 VL 47 IS 8 BP 1553 EP 1558 DI 10.1016/j.jacc.2005.10.075 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033AR UT WOS:000236819000007 PM 16630990 ER PT J AU Hoffmann, U Moselewski, F Nieman, K Jang, IK Ferencik, M Rahman, AM Cury, RC Abbara, S Joneidi-Jafari, H Achenbach, S Brady, TJ AF Hoffmann, U Moselewski, F Nieman, K Jang, IK Ferencik, M Rahman, AM Cury, RC Abbara, S Joneidi-Jafari, H Achenbach, S Brady, TJ TI Noninvasive assessment of plaque morphology and composition in culprit and stable lesions in acute coronary syndrome and stable lesions in stable angina by multidetector computed tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ELECTRON-BEAM TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; ARTERY-DISEASE; ATHEROSCLEROTIC LESIONS; CHEST-PAIN; HEART-ASSOCIATION; SPIRAL CT; FOLLOW-UP; DEATH AB OBJECTIVES The purpose of this study was to assess morphology and composition of culprit and stable coronary lesions by multidetector computed tomography (MDCT). BACKGROUND Noninvasivc identification of culprit lesions has the potential to improve noninvasive risk stratification in patients with acute chest pain. METHODS Thirty-seven patients with acute coronary syndrome (ACS) or stable angina underwent coronary 16-slice MDCT and invasive selective angiography. In all significant coronary lesions two observers measured the degree of stenosis, plaque area at stenosis, and remodeling index and assessed plaque composition. Differences between culprit lesions in patients with ACS and stable lesions in patients with ACS or stable angina were determined. RESULTS We analyzed 40 lesions with excellent image quality in 14 patients with ACS and 9 patients with stable angina. Culprit lesions in patients with ACS (n = 14) had significantly greater plaque area and a higher remodeling index than both stable lesions in patients with ACS (n = 13) and in patients with stable angina (n = 13) (17.5 +/- 5.9 mm(2) vs. 9.1 +/- 4.8 mm(2) vs. 13.5 +/- 10.7 mm(2), p = 0.02; and 1.4 +/- 0.3 vs. 1.0 +/- 0.4 vs. 1.2 +/- 0.3, p = 0.04, respectively). The prevalence of non-calcified plaque was 100%, 62%, and 77%, respectively, and the prevalence of calcified plaque was 71%, 92%, and 85%, respectively, in culprit lesions in patients with ACS and in stable lesions in patients with ACS or stable angina. CONCLUSIONS We introduce the concept of noninvasive detection and characterization of coronary atherosclerotic lesions in patients with ACS by MDCT. We identified differences in lesion morphology and plaque composition between culprit lesions in ACS and stable lesions in ACS or stable angina, consistent with previous intravascular ultrasound studies. C1 Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Div Cardiol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. RP Hoffmann, U (reprint author), Harvard Univ, Dept Radiol, Sch Med, Massachusetts Gen Hosp, 165 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org FU NHLBI NIH HHS [1 T32 HL076136-02] NR 38 TC 286 Z9 298 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 18 PY 2006 VL 47 IS 8 BP 1655 EP 1662 DI 10.1016/j.jacc.2006.01.041 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033AR UT WOS:000236819000023 PM 16631006 ER PT J AU Braunwald, E AF Braunwald, E TI Epilogue: What do clinicians expect from imagers? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID CORONARY-HEART-DISEASE; ATHEROSCLEROTIC PLAQUE; RISK-FACTOR; PREVENTION C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 9 TC 42 Z9 44 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 APR 18 PY 2006 VL 47 IS 8 SU C BP C101 EP C103 DI 10.1016/j.jacc.2005.10.072 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 034CZ UT WOS:000236903800015 PM 16631504 ER PT J AU Muller, JE Tawakol, A Kathiresan, S Narula, J AF Muller, JE Tawakol, A Kathiresan, S Narula, J TI New opportunities for identification and reduction of coronary risk - Treatment of vulnerable patients, arteries, and plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TOMOGRAPHY; LESIONS AB Advances in the understanding of the role of vulnerable plaque in the causation of coronary events, coupled with novel diagnostic and therapeutic approaches, create a new opportunity for progress against cardiovascular disease. The recognition that non-flow-limiting plaques often produce cardiac events has led to the development of invasive and non-invasive methods to identify such plaques prospectively. Treatments such as stenting, photodynamic therapy, and novel pharmaceutical agents are under consideration as methods to stabilize the vulnerable plaques and patients that might be detected, thereby enhancing both primary and secondary prevention. Despite the promise of the field, many issues remain to be resolved, including the focality versus systemic nature of the atherosclerotic process, the ability of detectors to identify the target for which they were developed and prove that such a target is linked to clinical events, and the efficacy of specific therapy. If vulnerable plaques and patients can be successfully identified and treated, there will be immense clinical benefits, accompanied by cost savings. C1 InfraReDx, Burlington, MA 01803 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. RP Muller, JE (reprint author), InfraReDx, 34 3rd Ave, Burlington, MA 01803 USA. EM jmuller@infraredx.com NR 18 TC 23 Z9 25 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 APR 18 PY 2006 VL 47 IS 8 SU C BP C2 EP C6 DI 10.1016/j.jacc.2005.12.044 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 034CZ UT WOS:000236903800002 PM 16631507 ER PT J AU Pitteloud, N Acierno, JS Meysing, A Eliseenkova, AV Ma, JH Ibrahimi, OA Metzger, DL Hayes, FJ Dwyer, AA Hughes, VA Yialamas, M Hall, JE Grant, E Mohammadi, M Crowley, WF AF Pitteloud, N Acierno, JS Meysing, A Eliseenkova, AV Ma, JH Ibrahimi, OA Metzger, DL Hayes, FJ Dwyer, AA Hughes, VA Yialamas, M Hall, JE Grant, E Mohammadi, M Crowley, WF TI Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE normosmia; FGFR1 ID GONADOTROPIN-RELEASING-HORMONE; FACTOR RECEPTOR 1; LUTEINIZING-HORMONE; CANDIDATE GENE; FGF RECEPTOR; HETEROGENEITY; DEFICIENCY; PUBERTY; GPR54; IDENTIFICATION AB Mutations in KAL1 and FGFR1 cause Kallmann syndrome (KS), whereas mutations in the GNRHR and GPR54 genes cause idiopathic hypogonadotropic hypogonadism with normal olfaction (nIHH). Mixed pedigrees containing both KS and nIHH have also been described; however, the genetic cause of these rare cases is unknown. We examined the FGFR1 gene in seven nIHH subjects who either belonged to a mixed pedigree (n = 5) or who had associated midline defects (n = 2). Heterozygous FGFR1 mutations were found in three of seven unrelated nIHH probands with normal MRI of the olfactory system: (i) G237S in an nIHH female and a KS brother; (it) (P722H and N724K) in an nIHH male missing two teeth and his mother with isolated hyposmia; and (iii) Q68OX in a nIHH male with cleft lip/palate and missing teeth, his brother with nIHH, and his father with delayed puberty. We show that these mutations lead to receptor loss-of-function. The Q680X leads to an inactive FGFR1, which lacks a major portion of the tyrosine kinase domain (TKD). The G237S mutation inhibits proper folding of D2 of the FGFR1 and likely leads to the loss of cell-surface expression of FGFR1. In contrast, the (P722H and N724K) double mutation causes structural perturbations in TKD, reducing the catalytic activity of TKD. We conclude that loss-of-function mutations in FGFR1 cause nIHH with normal MRI of the olfactory system. These mutations also account for some of the mixed pedigrees, thus challenging the current idea that KS and nIHH are distinct entities. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. British Columbia Childrens Hosp, Dept Endocrinol & Diabet, Vancouver, BC V6H 3V5, Canada. NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Bartlett Hall Extens 5,55 Fruit St, 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; Mohammadi, Moosa/0000-0003-2434-9437 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NICHD NIH HHS [R01 HD015788, R01 HD042708, R01 HD15788-19, R01 HD42708-03, T32 HD007396, U54 HD028138, U54 HD029164, U54HD28138-14]; NIDCR NIH HHS [R01 DE013686, R01 DE13686-05] NR 45 TC 123 Z9 129 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 APR 18 PY 2006 VL 103 IS 16 BP 6281 EP 6286 DI 10.1073/pnas.0600962103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 035KF UT WOS:000236999000041 PM 16606836 ER PT J AU Farokhzad, OC Cheng, JJ Teply, BA Sherifi, I Jon, S Kantoff, PW Richie, JP Langer, R AF Farokhzad, OC Cheng, JJ Teply, BA Sherifi, I Jon, S Kantoff, PW Richie, JP Langer, R TI Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE docetaxel; prostate cancer; targeted delivery; prostate-specific membrane antigen; poly(D,L-lactic-co-glycolic acid) (PLGA) ID PROSTATE-CANCER; MEMBRANE ANTIGEN; DRUG-DELIVERY; RNA MOLECULES; BRACHYTHERAPY; NANOSPHERES; DOCETAXEL; CELLS; PHARMACOKINETICS; INTERNALIZATION AB Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2'-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight loss of 7.7 +/- 4% vs. 18 +/- 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean +/- SD); n = 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of approximate to 300 mm(3)), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Harvard Univ, MIT, Ctr Canc Nanotechnol Excellence, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Farokhzad, OC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA. EM ofarokhzad@partners.org; rlanger@mit.edu RI Zhou, Feng/E-9510-2011; Jon, Sangyong/C-3725-2012; Dong, Ping/H-4011-2016 FU NCI NIH HHS [U54 CA119349, CA 119349]; NIBIB NIH HHS [EB003647, K08 EB003647] NR 43 TC 945 Z9 993 U1 58 U2 484 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 18 PY 2006 VL 103 IS 16 BP 6315 EP 6320 DI 10.1073/pnas.0601755103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 035KF UT WOS:000236999000047 PM 16606824 ER PT J AU Kim, ND Chou, RC Seung, E Tager, AM Luster, AD AF Kim, ND Chou, RC Seung, E Tager, AM Luster, AD TI A unique requirement for the leukotriene B4 receptor BLT1 for neutrophil recruitment in infl ammatory arthritis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID B-4 RECEPTOR; RHEUMATOID-ARTHRITIS; MURINE MODEL; INFLAMMATION; CHEMOTAXIS; PROGRESSION; INITIATION; ANTIBODY; PLAYS; MICE AB Neutrophil recruitment into tissue plays an important role in host defense and disease pathogenesis, including the inflammatory arthritides. A multitude of diverse chemoattractants have been implicated in neutrophil recruitment, suggesting that they have overlapping functions in mediating this critical biological response. However, here we demonstrate a unique, non-redundant role for the leukotriene B-4 receptor BLT1 in mediating neutrophil recruitment into the joint in the K/BxN mouse model of inflammatory arthritis. We demonstrate that neutrophil expression of BLT1 was absolutely required for arthritis generation and chemokine production in this model, and that specific BLT1 inhibition reversed established disease. Adoptive transfer of wild-type (WT) neutrophils restored arthritis and chemokine production in BLT1(-/-) mice. Surprisingly, the primary effect of the transferred WT neutrophils into BLT1(-/-) mice was to promote the entry of endogenous BLT1(-/-) neutrophils into the joints of these mice. However, continued joint inflammation was dependent on the presence of WT neutrophils, indicating an ongoing specific requirement for BLT1-activated neutrophils in mediating BLT1(-/-) neutrophil recruitment by other chemoattractants. These experiments demonstrate that neutrophil BLT1 functions in a novel and essential non - cellautonomous manner to enable the recruitment of additional neutrophils not expressing this receptor, thereby amplifying the inflammatory response in autoantibody-induced arthritis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Boston, MA 02114 USA. EM luster.andrew@mgh.harvard.edu FU NHLBI NIH HHS [K08 HL04087]; NIAID NIH HHS [R01 AI 050892, R01 AI050892]; NIAMS NIH HHS [K08 AR054094, T32 AR007258, T32 AR007258-28] NR 23 TC 147 Z9 150 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 17 PY 2006 VL 203 IS 4 BP 829 EP 835 DI 10.1084/jem.20052349 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000007 PM 16567386 ER PT J AU Keir, ME Liang, SC Guleria, I Latchman, YE Qipo, A Albacker, LA Koulmanda, M Freeman, GJ Sayegh, MH Sharpe, AH AF Keir, ME Liang, SC Guleria, I Latchman, YE Qipo, A Albacker, LA Koulmanda, M Freeman, GJ Sayegh, MH Sharpe, AH TI Tissue expression of PD-L1 mediates peripheral T cell tolerance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN-PRESENTING CELLS; COSTIMULATORY MOLECULES; EPITHELIAL-CELLS; B-LYMPHOCYTES; NOD MOUSE; IN-VIVO; MICE; IMMUNITY; FAMILY; B7-H1 AB Programmed death 1 (PD-1), an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. PD-1 has two ligands: PD-1 ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal cells, including pancreatic islet cells; and PD-L2, which is restricted to macrophages and dendritic cells. To investigate whether PD-L1 and PD-L2 have synergistic or unique roles in regulating T cell activation and tolerance, we generated mice lacking PD-L1 and PD-L2 (PD-L1/PD-L2(-/-) mice) and compared them to mice lacking either PD-L. PD-L1 and PD-L2 have overlapping functions in inhibiting interleukin-2 and interferon-gamma production during T cell activation. However, PD-L1 has a unique and critical role in controlling self-reactive T cells in the pancreas. Our studies with bone marrow chimeras demonstrate that PD-L1/PD-L2 expression only on antigen-presenting cells is insufficient to prevent the early onset diabetes that develops in PD-L1/PD-L2(-/-) non-obese diabetic mice. PD-L1 expression in islets protects against immunopathology after transplantation of syngeneic islets into diabetic recipients. PD-L1 inhibits pathogenic self-reactive CD4(+) T cell-mediated tissue destruction and effector cytokine production. These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions in mediating tissue tolerance. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Islet Transplantat Res Lab, Boston, MA 02114 USA. RP Sharpe, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM asharpe@rics.bwh.harvard.edu FU NCI NIH HHS [CA84500, R01 CA084500]; NIAID NIH HHS [P01 AI056299, AI041521, AI056299, AI39671, AI40614, AI54976, P01 AI039671, P01 AI041521, R01 AI040614, R01 AI054976] NR 37 TC 454 Z9 473 U1 4 U2 28 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 APR 17 PY 2006 VL 203 IS 4 BP 883 EP 895 DI 10.1084/jem.20051776 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000014 PM 16606670 ER PT J AU Steere, AC Klitz, W Drouin, EE Falk, BA Kwok, WW Nepom, GT Baxter-Lowe, LA AF Steere, AC Klitz, W Drouin, EE Falk, BA Kwok, WW Nepom, GT Baxter-Lowe, LA TI Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SURFACE PROTEIN-A; TREATMENT-RESISTANT; RHEUMATOID-ARTHRITIS; DISEASE SPIROCHETE; HLA-DR2 SUBTYPES; EPITOPE; CHAIN; OSPA; DNA; CEFTRIAXONE AB An association has previously been shown between antibiotic-refractory Lyme arthritis, the human histocompatibility leukocyte antigen (HLA)-DR4 molecule, and T cell recognition of an epitope of Borrelia burgdorferi outer-surface protein A (OspA(163-175)). We studied the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes in 121 patients with antibiotic-refractory or antibiotic-responsive Lyme arthritis and correlated these frequencies with in vitro binding of the OspA(163-175) peptide to 14 DRB molecules. Among the 121 patients, the frequencies of HLA-DRB1-DQA1-DQB1 haplotypes were similar to those in control subjects. However, when stratified by antibiotic response, the frequencies of DRB1 alleles in the 71 patients with antibiotic- refractory arthritis differed significantly from those in the 50 antibiotic- responsive patients ( log likelihood test, P = 0.006; exact test, P = 0.008; effect size, Wn = 0.38). 7 of the 14 DRB molecules (DRB1*0401, 0101, 0404, 0405, DRB5*0101, DRB1*0402, and 0102) showed strong to weak binding of OspA(163-175), whereas the other seven showed negligible or no binding of the peptide. Altogether, 79% of the antibiotic- refractory patients had at least one of the seven known OspA peptide-binding DR molecules compared with 46% of the antibiotic- responsive patients (odds ratio = 4.4; P < 0.001). We conclude that binding of a single spirochetal peptide to certain DRB molecules is a marker for antibiotic- refractory Lyme arthritis and might play a role in the pathogenesis of the disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Publ Hlth Res Inst, Oakland, CA 94720 USA. Univ Washington, Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. Univ Calif San Francisco, Immunogenet & Transplantat Lab, San Francisco, CA 94143 USA. RP Steere, AC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM asteere@partners.org OI Nepom, Gerald/0000-0002-8063-1464 FU NIAMS NIH HHS [AR-20358, R01 AR020358] NR 43 TC 91 Z9 95 U1 1 U2 8 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 APR 17 PY 2006 VL 203 IS 4 BP 961 EP 971 DI 10.1084/jem.20052471 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 036FH UT WOS:000237056000021 PM 16585267 ER PT J AU Sands, BE Blank, MA Diamond, RH Barrett, JP Van Deventer, SJ AF Sands, BE Blank, MA Diamond, RH Barrett, JP Van Deventer, SJ TI Maintenance infliximab does not result in increased abscess development in fistulizing Crohn's disease: results from the ACCENT II study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID FISTULAS; MANAGEMENT; THERAPY AB Background Rapid fistula healing may predispose Crohn's disease patients to abscess development. Aim Data from ACCENT II were analysed to determine whether fistula-related abscess development is affected by infliximab exposure. Methods Following infliximab 5 mg/kg infusions at weeks 0, 2 and 6, patients were evaluated for fistula response for two consecutive visits at least 4 weeks apart. Patients (N = 282) were randomized at week 14 to either placebo or infliximab 5 mg/kg every 8 weeks through week 46. If response was lost at or after week 22, patients could crossover to a 5 mg/kg higher infliximab dose. Fistula-related abscesses were diagnosed by physical examination or by imaging procedures according to usual practice. Results Infliximab exposure was approximately twofold higher for the infliximab maintenance group. Twenty-one (15%) patients in the infliximab maintenance group had at least one newly developed fistula-related abscess compared with 27 (19%) in the placebo maintenance group (P = 0.526). The proportion of patients with a new fistula-related abscess was similar regardless of whether or not patients crossed over to a 5 mg/kg higher infliximab dose. The number of fistula-related abscesses diagnosed over time did not differ between groups. Conclusion Abscess development in patients with fistulizing Crohn's disease is not dependent on cumulative infliximab exposure. C1 MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Centocor Inc, Malvern, PA 19355 USA. Univ Amsterdam, Amsterdam, Netherlands. RP Sands, BE (reprint author), MGH Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 14 TC 58 Z9 59 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR 15 PY 2006 VL 23 IS 8 BP 1127 EP 1136 DI 10.1111/j.1365-2036.2006.02878.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 027DB UT WOS:000236392800011 PM 16611273 ER PT J AU Deswal, A Bozkurt, B AF Deswal, A Bozkurt, B TI Comparison of morbidity in women versus men with heart failure and preserved ejection fraction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HYPERTENSIVE HYPERTROPHIC CARDIOMYOPATHY; GENDER-DIFFERENCES; MORTALITY; PREVALENCE; SURVIVAL AB Patients with heart failure (HF) and preserved ejection fraction (HF-PEF) constitute up to 30% to 50% of patients with HF, and HF-PEF affects women more often than men. Not much is known about the role of gender in the clinical presentation, symptoms, or disease severity of HF-PEF or about the contribution of these differences to gender differences in morbidity and mortality in patients with HF-PEF. This study examined gender differences in clinical presentation, hospitalization, and mortality in patients with HF-PEF (ejection fraction >= 50%) enrolled in the ancillary arm of the Digitalis Investigation Group trial. Time-to-event analysis was performed using Cox proportional-hazards modeling. The study cohort included 719 patients (378 men, 341 women). At baseline, compared with men, women were older and had greater clinical severity of HF, as evidenced by worse New York Heart Association functional class, more frequent symptoms and signs of HF, and more treatment with diuretics. Ischemia was identified as the primary cause of HF in 46% of women and 56% of men (p = 0.01). During a median follow-up of 39 months, crude mortality was similar in women and men (24.6% and 24.3%, p = 0.93), but more, women were hospitalized for HF (26.7% vs 15.9%, p < 0.001). After adjustment for baseline differences, female gender was an independent predictor of lower mortality (hazard ratio 0.59, 95% confidence interval 0.43 to 0.82), but HF hospitalization rates were similar between men and women (hazard ratio 1.09, 95% confidence interval 0.77 to 1.53). In conclusion, although the clinical manifestations of HF appear to be more severe in women with HF-PEF, after adjustment for baseline clinical differences, HF hospitalizations are not increased and survival expectancy is better for women compared with men. (c) 2006 Elsevier Inc. All rights reserved. C1 Michael E DeBakey Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Houston, TX USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Deswal, A (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Winters Ctr Heart Failure Res, Cardiol Sect, Dept Med, Houston, TX USA. EM adeswal@bcm.tmc.edu NR 20 TC 30 Z9 33 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 APR 15 PY 2006 VL 97 IS 8 BP 1228 EP 1231 DI 10.1016/j.amjcard.2005.11.042 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 038XO UT WOS:000237263000020 PM 16616031 ER PT J AU Chen, HL Schernhammer, E Schwarzschild, MA Ascherio, A AF Chen, HL Schernhammer, E Schwarzschild, MA Ascherio, A TI A prospective study of night shift work, sleep duration, and risk of Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; Parkinson disease; sleep; sleep disorders; circadian rhythm ID URIC-ACID LEVELS; NURSES HEALTH; WOMEN; MELATONIN; STRESS; SERUM; DEPRESSION; DISORDERS; ANXIETY; CANCER AB The authors prospectively investigated whether working rotating night shifts was associated with the risk of Parkinson's disease among 84,794 female nurses who reported years of night shift work in 1988 (the US Nurses' Health Study). After 975,912 person-years of follow-up (1988-2000), 181 incident Parkinson's disease cases were documented. Compared with nurses who never worked rotating night shifts, those with 15 years or more of night shift work had a 50% lower risk of Parkinson's disease after adjustment for age and smoking (95% confidence interval: 0.26, 0.97; p(trend) = 0.01). Sleep duration was positively associated with Parkinson's disease risk: The relative risk was 1.84 (95% confidence interval: 0.99, 3.42) when comparing nurses who reported 9 or more hours of sleep per day with those who slept 6 hours or less (p(trend) = 0.005). These data suggest that working night shifts may be protective against Parkinson's disease or that low tolerance for night shift work is an early marker of Parkinson's disease. Conversely, habitual longer sleep duration may be an earlier marker of Parkinson's disease. Because of the novelty and the exploratory nature of these findings, confirmation is needed. C1 NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, NIH, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS; NCI NIH HHS [CA87969]; NINDS NIH HHS [NS35624, NS48468] NR 29 TC 30 Z9 33 U1 0 U2 10 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 APR 15 PY 2006 VL 163 IS 8 BP 726 EP 730 DI 10.1093/aje/kwj096 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 030DE UT WOS:000236612700006 PM 16495472 ER PT J AU Kacmarek, RM Wiedemann, HP Lavin, PT Wedel, MK Tutuncu, AS Slutsky, AS AF Kacmarek, RM Wiedemann, HP Lavin, PT Wedel, MK Tutuncu, AS Slutsky, AS TI Partial liquid ventilation in adult patients with acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; liquid ventilation; mechanical ventilation; partial liquid ventilation ID ACUTE LUNG INJURY; PULMONARY BLOOD-FLOW; GAS-EXCHANGE; MECHANICAL VENTILATION; NEUTROPHIL ACCUMULATION; PERFLUBRON; MORTALITY; FAILURE; MODEL; TRIAL AB Rationale: Despite recent clinical trials demonstrating improved outcome in acute respiratory distress syndrome (ARDS), mortality remains high. Partial liquid ventilation (PLV) using perfluorocarbons has been shown to improve oxygenation and decrease lung injury in various animal models. Objective: To determine if PLV would have an impact on outcome in patients with ARDS. Methods: Patients with ARDS were randomized to (1) conventional mechanical ventilation (CMV; n = 107), (2) "low-dose" perfluoro-carbon (10 ml/kg; In = 99), and (3) "high-dose" perfluorocarbon (20 ml/kg; n = 105). Patients in all three groups were ventilated using volume ventilation, V-t <= 10 ml/kg predicted body weight, rate <= 25/min, inspiratory-to-expiratory ratio <= 1:1, F-lO2 >= 0.5, and positive end-expiratory pressure >= 13 cm H2O. Results:The 28-d mortality in the CMV group was 15%, versus 26.3% in the low-dose (p = 0.06) and 19.1% in the high-dose (p = 0.39) PLV groups. There were more ventilator-free days in the CMV group (13.0 +/- 9.3) compared with both the low-dose (7.4 +/- 8.5; p < 0.001) and high-dose (9.9 +/- 9.1; p = 0.043) groups. There were more pneumothoraces, hypoxic episodes, and hypotensive episodes in the PLV patients. Conclusions: PLV at both high and low doses did not improve outcome in ARDS compared with CMV and cannot be recommended for patients with ARDS. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Averion Inc, Framingham, MA USA. Boston Biostat Res Fdn Inc, Framingham, MA USA. Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. Clin Res Alliance Pharmaceut Corp, San Diego, CA USA. Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Surg, Toronto, ON, Canada. Univ Toronto, Dept Biomed Engn, Toronto, ON, Canada. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org RI Slutsky, Arthur/A-6013-2008; OI Slutsky, Arthur/0000-0002-6063-3876; Wiedemann, Herbert/0000-0002-4587-4401 NR 36 TC 87 Z9 98 U1 0 U2 5 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 APR 15 PY 2006 VL 173 IS 8 BP 882 EP 889 DI 10.1164/rccm.200508-1196OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 032JK UT WOS:000236770500011 PM 16254269 ER PT J AU Katz, ES Marcus, CL White, DP AF Katz, ES Marcus, CL White, DP TI Influence of airway pressure on genioglossus activity during sleep in normal children SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE critical closing pressure; genioglossus EMG; intraoral surface electrode ID LONG-TERM FACILITATION; NREM SLEEP; ELECTRICAL-STIMULATION; DEVELOPMENTAL-CHANGES; EPISODIC HYPOXIA; PASSIVE PHARYNX; APNEA; AROUSAL; MUSCLE; OCCLUSION AB Rationale: Most children with obstructive sleep apnea are able to sustain stable breathing during portions of sleep, despite an anatomic predisposition toward airway collapse. This suggests that additional determinants of airway patency are active, such as neuromuscular compensation. Objectives/Methods: Using a custom intraoral surface electrode to record pharyngeal dilator muscle activity (the genioglossus [EMGgg]), we evaluated the muscle, ventilatory, and arousal responses to negative-pressure challenges during sleep in 19 healthy control children. Measurements and Main Results: In response to these challenges, we observed (1) marked variability in individual EMGgg responsiveness (peak EMGgg [mean +/- SD], 214 +/- 101% baseline), which was consistent within subjects; (2) a relationship between EMGgg activity and inspiratory flow and airway collapsibility; (3) reflex increases in flow (peak flow increase from challenge breaths 1-5 [mean +/- SD], 49 41% baseline) and respiratory rate often sufficient to sustain minute ventilation near baseline levels, without arousal; and (4) arousal threshold to be highest in stage 4, intermediate in stage 2, and lowest in REM sleep. Conclusions: Healthy children have wide variation in upper airway neuromuscular compensatory responses and arousal thresholds that could represent intermediate phenotypes affecting the expression of sleep apnea. Children with robust upper airway neuromuscular responsiveness, or a very high arousal threshold, may be able to sustain minute ventilation when challenged with negative airway pressure. C1 Massachusetts Gen Hosp, Div Pediat Pulmonol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Sleep Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Sleep Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Katz, ES (reprint author), Massachusetts Gen Hosp, Div Pediat Pulmonol, 55 Fruit St, Boston, MA 02114 USA. EM eskatz@partners.org FU NCRR NIH HHS [M01 RR02172]; NHLBI NIH HHS [R01 HL048531, 1 P50 HL60292, HL073238-01]; PHS HHS [58585] NR 36 TC 24 Z9 25 U1 0 U2 2 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 APR 15 PY 2006 VL 173 IS 8 BP 902 EP 909 DI 10.1164/rccm.200509-1450OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 032JK UT WOS:000236770500014 PM 16439714 ER PT J AU Covinsky, K AF Covinsky, K TI Aging, arthritis, and disability SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Editorial Material ID FUNCTIONAL STATUS; DISABLEMENT PROCESS; OLDER PERSONS; DEPENDENCE; ADULTS; ELDERS; RISK C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Covinsky, K (reprint author), 4150 Clement 181G, San Francisco, CA 94121 USA. EM covinsky@medicine.ucsf.edu NR 13 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2006 VL 55 IS 2 BP 175 EP 176 DI 10.1002/art.21861 PG 2 WC Rheumatology SC Rheumatology GA 033EV UT WOS:000236830400003 PM 16583390 ER PT J AU Ganz, DA Chang, JT Roth, CP Guan, N Kamberg, CJ Niu, F Reuben, DB Shekelle, PG Wenger, NS Maclean, CH AF Ganz, DA Chang, JT Roth, CP Guan, N Kamberg, CJ Niu, F Reuben, DB Shekelle, PG Wenger, NS Maclean, CH TI Quality of osteoarthritis care for community-dwelling older adults SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE osteoarthritis; quality of care; quality improvement; primary care; health status ID VULNERABLE ELDERS; UNITED-STATES; RISK-FACTORS; HEALTH; INTERVENTION; PREVALENCE; VALIDATION; ARTHRITIS; KNEE; HIP AB Objective. To describe the quality of osteoarthritis care provided to community-dwelling elderly patients and to characterize arthritis-related function in these patients. Methods. Two medical groups in the western United States participated in a practice-redesign intervention targeted at falls and mobility disorders, incontinence, and cognitive impairment, but not osteoarthritis. From 339 individuals reporting a diagnosis of arthritis, we collected information on demographics, functional status, and quality of care via patient interviews and mailed questionnaires. Eight quality indicators measured osteoarthritis care: 4 indicators measuring the provision of effective osteoarthritis care (osteoarthritis treatment indicators) and 4 measuring the provision of safe osteoarthritis care (medication safety indicators). Results. The mean +/- SD Short Form 12 physical component summary score was 35 +/- 11 points, indicating a physically frail population. The overall indicator pass rate was 57.0% (95% confidence interval [95% CI] 53.9-60.2). Pass rates were higher for indicators of osteoarthritis treatment (63.5%, 95% CI 59.8-67.2) than for indicators of medication safety (43.8%, 95% CI 38.2-49.4). Patients with hip or knee pain had mean +/- SD Western Ontario and McMaster Universities Osteoarthritis Index pain, stiffness, and function scores of 6.0 +/- 4.0, 3.1 +/- 1.7, and 25 +/- 12 points, respectively. Conclusion. Quality of osteoarthritis care for older adults is suboptimal, particularly with regard to medication safety. Given the high prevalence of osteoarthritis in older age groups, the population impact of any improvement in quality would be substantial. Quality improvement efforts for osteoarthritis should target appropriate use of and counseling regarding medications, as well as underuse of efficacious therapy for osteoarthritis. C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Vet Affairs Greater Los Angeles Hlth Care Syst, STAR Program, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. RP Ganz, DA (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Vet Affairs Greater Los Angeles Hlth Care Syst, STAR Program, 911 Broxton Plaza,3rd Floor, Los Angeles, CA 90024 USA. EM dganz@mednet.ucla.edu NR 19 TC 53 Z9 53 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2006 VL 55 IS 2 BP 241 EP 247 DI 10.1002/art.21844 PG 7 WC Rheumatology SC Rheumatology GA 033EV UT WOS:000236830400012 PM 16583414 ER PT J AU Dally, S Bredoux, R Corvazier, E Andersen, JP Clausen, JD Dode, L Fanchaouy, M Gelebart, P Monceaw, V Del Monte, F Gwathmey, JK Hajjar, R Chaabane, C Bobe, R Raies, A Enouf, J AF Dally, S Bredoux, R Corvazier, E Andersen, JP Clausen, JD Dode, L Fanchaouy, M Gelebart, P Monceaw, V Del Monte, F Gwathmey, JK Hajjar, R Chaabane, C Bobe, R Raies, A Enouf, J TI Ca2+-ATPases in non-failing and failing heart: evidence for a novel cardiac sarco/endoplasmic reticulum Ca2+-ATPase 2 isoform (SERCA2c) SO BIOCHEMICAL JOURNAL LA English DT Article DE endoplasmic reticulum; heart failure; human embryonic kidney 293 cell (HEK-293 cell); isoform; plasma membrane Ca2+-ATPase (PMCA); sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) ID TRANSIENT KINETIC ANALYSES; MEMBRANE CALCIUM-PUMP; SARCOPLASMIC-RETICULUM; PLASMA-MEMBRANE; DILATED CARDIOMYOPATHY; MESSENGER-RNA; STEADY-STATE; CA2+ PUMP; FUNCTIONAL DIFFERENCES; HUMAN MYOCARDIUM AB We recently documented the expression of a novel human mRNA variant encoding a yet uncharacterized SERCA [SR (sarcoplasmic reticulum)/ER (endoplasmic reticulum) Ca2+-ATPase] protein, SERCA2c [Gelebart, Martin, Enouf and Papp (2003) Biochem. Biophys. Res. Commun. 303, 676-684]. In the present study, we have analysed the expression and functional characteristics of SERCA2c relative to SERCA2a and SERCA2b isoforms upon their stable heterologous expression in HEK-293 cells (human embryonic kidney 293 cells). All SERCA2 proteins induced an increased Ca2+ content in the ER of intact transfected cells. In microsomes prepared from transfected cells, SERCA2c showed a lower apparent affinity for cytosolic Ca2+ than SERCA2a and a catalytic turnover rate similar to SERCA2b. We further demonstrated the expression of the endogenous SERCA2c protein in protein lysates isolated from heart left ventricles using a newly generated SERCA2c-specific antibody. Relative to the known uniform distribution of SERCA2a and SERCA2b in cardiomyocytes of the left ventricle tissue, SERCA2c was only detected in a confined area of cardiomyocytes, in close proximity to the sarcolemma. This finding led us to explore the expression of the presently known cardiac Ca2+-ATPase isoforms in heart failure. Comparative expression of SERCAs and PMCAs (plasma-membrane Ca2+-ATPases) was performed in four nonfailing hearts and five failing hearts displaying mixed cardio-myopathy and idiopathic dilated cardiomyopathies. Relative to normal subjects, cardiomyopathic patients express more PMCAs than SERCA2 proteins. Interestingly, SERCA2c expression was significantly increased (166+26%) in one patient. Taken together, these results demonstrate the expression of the novel SERCA2c isoform in the heart and may point to a still unrecognized role of PMCAs in cardiomyopathies. C1 Hop Lariboisiere, INSERM, U689, IFR139, F-75475 Paris 10, France. Aarhus Univ, Inst Physiol & Biophys, Dept Physiol, Aarhus, Denmark. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Catholic Univ Louvain, Physiol Lab, Louvain, Belgium. Fac Sci Tunis, Lab Microorganism & Biomol Act, Tunis, Tunisia. RP Enouf, J (reprint author), Hop Lariboisiere, INSERM, U689, IFR139, 8 Rue Guy Patin, F-75475 Paris 10, France. EM jocelyne.enouf@larib.inserm.fr RI BOBE, Regis/F-4951-2016 OI BOBE, Regis/0000-0002-8225-9117 NR 43 TC 48 Z9 50 U1 0 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 15 PY 2006 VL 395 BP 249 EP 258 DI 10.1042/BJ20051427 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033IL UT WOS:000236840400003 PM 16402920 ER PT J AU Myin-Germeys, I Holt, DJ Taylor, SF Gur, R AF Myin-Germeys, I Holt, DJ Taylor, SF Gur, R TI Stress reactivity, the emotional phenotype and psychosis: Understanding the roots of vulnerability SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Maastricht Univ, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 10 BP 4S EP 4S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300012 ER PT J AU Spencer, KM McCarley, RW AF Spencer, KM McCarley, RW TI Gamma-band oscillations and cortical circuit dysfunction in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 14 BP 5S EP 5S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300016 ER PT J AU Pitman, RK AF Pitman, RK TI Translational model of PTSD updated: Role of reconsolidation and treatment implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 46 BP 15S EP 15S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300048 ER PT J AU Weiss, AP AF Weiss, AP TI Source memory and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 63 BP 20S EP 20S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300065 ER PT J AU Kennedy, A Wood, AE Saxon, A Harvey, M Jurik, J Kilzieh, N Lofgreen, C Sorem, C Crandall, DA Graunke, B Tapp, A AF Kennedy, A Wood, AE Saxon, A Harvey, M Jurik, J Kilzieh, N Lofgreen, C Sorem, C Crandall, DA Graunke, B Tapp, A TI Quetiapine for the treatment of cocaine dependence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Tacoma, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 75 BP 23S EP 24S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300077 ER PT J AU Viguera, AC Mogielnicki, J Whitfield, TH Halperin, L Obdeyn, M Shavel-Jessop, S Sherman, J Cohen, LS AF Viguera, AC Mogielnicki, J Whitfield, TH Halperin, L Obdeyn, M Shavel-Jessop, S Sherman, J Cohen, LS TI Neurobehavioral outcome following exposure to lithium: What happens to lithium babies? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychol, Boston, MA 02114 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 74 BP 23S EP 23S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300076 ER PT J AU Boyd, JA Pierre, JM Adamson, CF Guzik, LH Mahgerefteh, S Wirshing, DA Wirshing, WC AF Boyd, JA Pierre, JM Adamson, CF Guzik, LH Mahgerefteh, S Wirshing, DA Wirshing, WC TI Aripiprazole-associated new-onset diabetes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 76 BP 24S EP 24S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300078 ER PT J AU Moore, CM Biederman, J Wozniak, J Mick, E Aleardi, M Wardrop, M Dougherty, M Dougherty, M Harpold, TL Hammerness, P Randall, E Renshaw, PF AF Moore, CM Biederman, J Wozniak, J Mick, E Aleardi, M Wardrop, M Dougherty, M Dougherty, M Harpold, TL Hammerness, P Randall, E Renshaw, PF TI Effects of risperidone on anterior cingulate cortex glutamate in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 78 BP 24S EP 24S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300080 ER PT J AU Biederman, J AF Biederman, J TI An open-label trial of aripiprazole in youth with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 80 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300082 ER PT J AU Wolfe, DJ Dickey, CC Seidman, LJ Morocz, IA Thermenos, HW Dreusicke, MH Paynter, VR Voglmaier, MM Niznikiewicz, MA Shenton, ME McCarley, RW AF Wolfe, DJ Dickey, CC Seidman, LJ Morocz, IA Thermenos, HW Dreusicke, MH Paynter, VR Voglmaier, MM Niznikiewicz, MA Shenton, ME McCarley, RW TI Altered cortical activity during visual working memory in schizotypal personality disorder: A pilot fMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 99 BP 31S EP 31S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300101 ER PT J AU Marder, SR Crandall, D Pultz, J Carson, W Gutierrez-Esteinou, R Van Tran, Q Marcus, R AF Marder, SR Crandall, D Pultz, J Carson, W Gutierrez-Esteinou, R Van Tran, Q Marcus, R TI The effectiveness of aripiprazole in patients with schizophrenia experiencing high or low agitation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Greater LA Hlth Care Syst, Los Angeles, CA USA. Bristol Myers Squibb, Neurosci, Plainsboro, NJ USA. 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Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 101 BP 32S EP 32S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300103 ER PT J AU Gerothanassis, D Dickey, CC Shenton, ME Niznikiewicz, MA Voglmaier, MM Cohen, AS Bushell, GL Dreusicke, MH Seidman, LJ McCarley, RW AF Gerothanassis, D Dickey, CC Shenton, ME Niznikiewicz, MA Voglmaier, MM Cohen, AS Bushell, GL Dreusicke, MH Seidman, LJ McCarley, RW TI A pilot volumetric MRI study of the prefrontal cortex in individuals with schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Boston VA Healthcare Syst, Dept Psychiat, Boston, MA USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 112 BP 35S EP 35S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300114 ER PT J AU Warden, D Rush, AJ Fava, M Trivedi, M Wisniewski, SR Nierenberg, A Hollon, SD Howland, R Zisook, S Stewart, JW Gaynes, BN AF Warden, D Rush, AJ Fava, M Trivedi, M Wisniewski, SR Nierenberg, A Hollon, SD Howland, R Zisook, S Stewart, JW Gaynes, BN TI Pretreatment predictors of outpatient attrition during citalopram treatment for depression: A sequenced treatment alternatives to relieve depression report SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. 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James J Peters VAMC, MIRECC, VA VISN3, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 151 BP 46S EP 47S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300153 ER PT J AU Iosifescu, DV Moore, C Deckersbach, T Nierenberg, AA Renshaw, PF Gironde, SVM Sachs, GS AF Iosifescu, DV Moore, C Deckersbach, T Nierenberg, AA Renshaw, PF Gironde, SVM Sachs, GS TI Hippocampal neuronal viability and treatment with galantamine-ER for cognitive dysfunction in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 174 BP 54S EP 54S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300176 ER PT J AU Salisbury, DF Adler, M Brown, C Shenton, ME McCarley, RW AF Salisbury, DF Adler, M Brown, C Shenton, ME McCarley, RW TI P300, cognition, and symptoms at first hospitalization and longitudinally in first episode schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 175 BP 54S EP 54S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300177 ER PT J AU Kubicki, M Bushell, GL Markant, D Dreusicke, M Park, HJ Bouix, S Westin, CF Kikinis, R McCarley, RW Shenton, ME AF Kubicki, M Bushell, GL Markant, D Dreusicke, M Park, HJ Bouix, S Westin, CF Kikinis, R McCarley, RW Shenton, ME TI In-vivo diffusion fiber tractography suggests disruptions in connectivity between the frontal and temporal lobes in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Psychiat Neuroimaging Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Radiol Lab Math Imaging, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Surg Planning Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Lab, Clin Neurosci Div, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 183 BP 57S EP 57S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300185 ER PT J AU Frey, BN Nery, FG Stanley, JA Chen, HH Nicoletti, MA Hatch, JP Monkul, ES Caetano, SC Ortiz, O Soares, JC AF Frey, BN Nery, FG Stanley, JA Chen, HH Nicoletti, MA Hatch, JP Monkul, ES Caetano, SC Ortiz, O Soares, JC TI Lower creatine plus phosphocreatine in the left dorsolateral prefrontal cortex in unmedicated bipolar disorder subjects: A magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Bipolar Disorders Program, Porto Alegre, RS, Brazil. S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. NR 0 TC 0 Z9 0 U1 2 U2 2 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 185 BP 58S EP 58S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300187 ER PT J AU Nery, FG Hatch, JP Glahn, D Nicoletti, M Monkul, ES Sanches, M Najt, P Koji, M Bowden, C Cloninger, CR Soares, JC AF Nery, FG Hatch, JP Glahn, D Nicoletti, M Monkul, ES Sanches, M Najt, P Koji, M Bowden, C Cloninger, CR Soares, JC TI Chronicity and severity in major depressive disorder and their relationship with personality traits SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, MOOD CNS Program, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Washington, Sch Med, Dept Psychiat, St Louis, MO USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX USA. RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 212 BP 66S EP 66S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300214 ER PT J AU Chen, HH Jeffrey, SA Caetano, SC Nicoletti, M Hatch, HP Monkul, SE Nery, FG Manoela, F Osvaldo, O Soares, JC AF Chen, HH Jeffrey, SA Caetano, SC Nicoletti, M Hatch, HP Monkul, SE Nery, FG Manoela, F Osvaldo, O Soares, JC TI A multi-voxel 1H magnetic resonance spectroscopy investigation in bipolar disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Wayne State Univ, Sch Med, Detroit, MI 78284 USA. UTHSCSA, Dept Psychiat, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 214 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300216 ER PT J AU Kubicki, M Ungar, L Wible, CG Nestor, PG Elizabeth, C Westin, CF Kikinis, R Shenton, ME McCarley, RW AF Kubicki, M Ungar, L Wible, CG Nestor, PG Elizabeth, C Westin, CF Kikinis, R Shenton, ME McCarley, RW TI Executive attentional network-functional activation and anatomical integrity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Boston, MA USA. Harvard Univ, Sch Med, Clin Neurosci Div, Neurosci Lab,Dept Psychiat, Brockton, MA USA. VA Boston Healthcare Syst, Brockton, MA USA. Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Boston, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 266 BP 83S EP 83S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300268 ER PT J AU Goodman, M Flory, J Koenigsberg, H Siever, L New, A AF Goodman, M Flory, J Koenigsberg, H Siever, L New, A TI Aggressive responding in borderline personality disorder - Baseline differences and treatment effects of a cognitive behavioral therapy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 275 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300277 ER PT J AU Hu, XZ Rush, AJ Charney, DS Wilson, AF Sorant, AJM Papanicolaou, GJ Fava, M Madhukar, MH Wisniewski, S Laje, G Buervenich, S McMahon, FJ Manji, H Lipsky, RH AF Hu, XZ Rush, AJ Charney, DS Wilson, AF Sorant, AJM Papanicolaou, GJ Fava, M Madhukar, MH Wisniewski, S Laje, G Buervenich, S McMahon, FJ Manji, H Lipsky, RH TI Serotonin transporter promoter polymorphism predicting increased transcription is associated with tolerability to citalopram treatment in the STAR*D effectiveness trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Mt Sinai Hosp, Albert Einstein Sch Med, New York, NY 10029 USA. NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIMH, Mol Pathophysiol Lab, Mood & Anxiety Program, NIH, Bethesda, MD 20892 USA. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 315 BP 97S EP 97S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300311 ER PT J AU Fava, M AF Fava, M TI Study design and clinical outcomes for levels 1 & 2 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 338 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300334 ER PT J AU Biederman, J AF Biederman, J TI An open-label study of divalproex sodium monotherapy in youth with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 374 BP 114S EP 114S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300370 ER PT J AU Biederman, J AF Biederman, J TI Comparative and acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention deficit hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 376 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300372 ER PT J AU Chen, HH Jeffrey, SA Nicoletti, M Hatch, J Sanches, M Caetano, SC Fonseca, M Najt, P Matsuo, K Monkul, SE Peluso, M Silva, LP Osvaldo, O Soares, JC AF Chen, HH Jeffrey, SA Nicoletti, M Hatch, J Sanches, M Caetano, SC Fonseca, M Najt, P Matsuo, K Monkul, SE Peluso, M Silva, LP Osvaldo, O Soares, JC TI Gender effects on brain metabolite levels in unipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 UTHSCSA, Dept Psychiat, San Antonio, TX USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. 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Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 375 BP 115S EP 115S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300371 ER PT J AU Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Huang, XH Dittmann, R Biederman, J AF Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Huang, XH Dittmann, R Biederman, J TI Olanzapine in the treatment of acute mania in adolescents with bipolar I disorder; A 3-week randomized double-blind placebo-controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Stony Brook Univ, Sch Med, Stony Brook, NY USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Lilly Deutschland, Dept Med, Bad Homburg, Germany. Univ Hamburg, Childrens Hosp, Psychosomat Dept, Hamburg, Germany. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 387 BP 118S EP 119S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300383 ER PT J AU Joffe, H Dorsey, C Thurston, R Yehezkel, R Somley, B Petrillo, L Viguera, A Hall, JE Cohen, LS AF Joffe, H Dorsey, C Thurston, R Yehezkel, R Somley, B Petrillo, L Viguera, A Hall, JE Cohen, LS TI Predictors of improvement in mood in symptomatic peri/postmenopausal women SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Sleep Lab, Belmont, MA 02178 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Internal Med, Reprod Endocrine Unit, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 393 BP 120S EP 121S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300389 ER PT J AU Sachs, GS Crandall, D Rollin, L Forbes, A Gutierrez-Esteinou, R Pikalov, A Sanchez, R AF Sachs, GS Crandall, D Rollin, L Forbes, A Gutierrez-Esteinou, R Pikalov, A Sanchez, R TI Effect of high or low levels of agitation on the Antimanic response to aripiprazole SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Bristol Myers Squibb Co, Global Clin Res, Pharmaceut Res Inst, Wallingford, CT 06492 USA. Otsuka Pharmaceut Co Ltd, Global Dev & Commercializat, Princeton, NJ USA. Bristol Myers Squibb Co, Global Med Affairs, Lawrenceville, NJ USA. Otsuka Pharmaceut Co Ltd, US Med Affairs, Rockville, MD 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 392 BP 120S EP 120S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300388 ER PT J AU Fonseca, M Caetano, SC Chen, HH Nicoletti, M Stanley, JA Hatch, JP Olvera, RL Hunter, K Ortiz, O Pliszka, S Soares, JC AF Fonseca, M Caetano, SC Chen, HH Nicoletti, M Stanley, JA Hatch, JP Olvera, RL Hunter, K Ortiz, O Pliszka, S Soares, JC TI A proton chemical shift Imaging study in pediatric major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Mood CNS Program, Dept Psychiat,Div Mood & Anxiety Disorders, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Psychiat Serv, Audie L Murphy Div, San Antonio, TX USA. Univ Fed Rio Grande Sul, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Child & Adolescent Psychiat, San Antonio, TX 78284 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 397 BP 122S EP 122S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300393 ER PT J AU Mintzer, JE Crandall, D Pultz, J Carson, W Gutierrez-Esteinou, R Whitehead, R Breader, C AF Mintzer, JE Crandall, D Pultz, J Carson, W Gutierrez-Esteinou, R Whitehead, R Breader, C TI Efficacy of aripiprazole in highly agitated patients with psychosis of Alzheimer's disease SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Med Univ S Carolina, Alzheimers Res & Clin Program, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Bristol Myers Squibb Co, Neurosci, Plainsboro, NJ USA. Bristol Myers Squibb Co, Biostat & Data Management, Clin Res, Wallingford, CT 06492 USA. Otsuka Pharmaceut Co Ltd, Global Med Affairs, Princeton, NJ USA. Bristol Myers Squibb Co, Global Med Affairs, Lawrenceville, NJ USA. Otsuka Pharmaceut Co Ltd, US Med Affairs, Rockville, MD 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 417 BP 128S EP 129S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767300413 ER PT J AU Roffman, JL Weiss, AP Purcell, S Freudenreich, O Henderson, DC Wong, DH Halsted, CH Goff, DC AF Roffman, JL Weiss, AP Purcell, S Freudenreich, O Henderson, DC Wong, DH Halsted, CH Goff, DC TI Interactive effects of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and serum folate status on negative symptoms of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Calif Davis, Sacramento, CA 95817 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 425 BP 131S EP 131S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301002 ER PT J AU Iosifescu, DV Moore, C Deckersbach, T Nierenberg, AA Renshaw, PF Gironde, SVM Sachs, GS AF Iosifescu, DV Moore, C Deckersbach, T Nierenberg, AA Renshaw, PF Gironde, SVM Sachs, GS TI Hippocampal neuronal viability and treatment with galantamine-ER for cognitive dysfunction in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 448 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301025 ER PT J AU Boyd, JA Daigdigan, DM Wirshing, DA Guzik, LH Mahgerefteh, S Wirshing, WC AF Boyd, JA Daigdigan, DM Wirshing, DA Guzik, LH Mahgerefteh, S Wirshing, WC TI Assessment of pharmacist-run medication education group for inpatients in a schizophrenia ward SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 450 BP 139S EP 139S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301027 ER PT J AU Frey, BN Nery, FG Stanley, JA Chen, HH Nicoletti, MA Hatch, JP Monkul, ES Caetano, SC Ortiz, O Soares, JC AF Frey, BN Nery, FG Stanley, JA Chen, HH Nicoletti, MA Hatch, JP Monkul, ES Caetano, SC Ortiz, O Soares, JC TI Lower creatine plus phosphocreatine in the left dorsolateral prefrontal cortex in unmedicated bipolar disorder subjects: A magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Fed Rio Grande do Sul, Dept Biochem, Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Bipolar Disorders Program, Porto Alegre, RS, Brazil. S Texas Vet Hlth Care Syst, Dept Psychiat, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR 15 PY 2006 VL 59 IS 8 SU S MA 458 BP 141S EP 141S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301035 ER PT J AU Milad, MR Goldstein, JM Orr, SP Wedig, MM Klibanski, A Pitman, RK Rauch, SL AF Milad, MR Goldstein, JM Orr, SP Wedig, MM Klibanski, A Pitman, RK Rauch, SL TI Fear conditioning and extinction: Influence of sex and menstrual cycle in healthy humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Neuroendocrine Unit, Charlestown, MA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 463 BP 143S EP 143S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301040 ER PT J AU Britton, JC Shin, LM Williams, D Wedig, MM Rauch, SL Barrett, LF Wright, CI AF Britton, JC Shin, LM Williams, D Wedig, MM Rauch, SL Barrett, LF Wright, CI TI Neural activation in response to schematic and human angry faces SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tufts Univ, Medford, MA 02155 USA. Harvard Univ, Cambridge, MA 02138 USA. Boston Coll, Chestnut Hill, MA 02167 USA. RI Britton, Jennifer/J-4501-2013 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 469 BP 144S EP 144S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301046 ER PT J AU Spencer, KM McCarley, RW AF Spencer, KM McCarley, RW TI Cortical circuitry abnormalities and gamma oscillations in schizophrenia: A computational modeling study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 480 BP 147S EP 148S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301057 ER PT J AU Zunta, GB Caetano, SC Nlcoletti, M Hatch, JP Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Soares, JC AF Zunta, GB Caetano, SC Nlcoletti, M Hatch, JP Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Soares, JC TI Illness duration and total brain gray matter in bipolar disorder: Evidence for neurodegeneration? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Sao Paulo Med, Sao Paulo, Brazil. Univ Udine, Pathol & Expt & Clin Med Sect Psychiat, I-33100 Udine, Italy. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 487 BP 150S EP 150S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301064 ER PT J AU Nery, FG Stanley, JA Chen, HH Nicoletti, M Hatch, JP Monkul, ES Caetano, SC Sanches, M Najt, P Peluso, M Silva, LP Ortiz, O Soares, JC AF Nery, FG Stanley, JA Chen, HH Nicoletti, M Hatch, JP Monkul, ES Caetano, SC Sanches, M Najt, P Peluso, M Silva, LP Ortiz, O Soares, JC TI Glutamatergic abnormalities in dorsolateral prefrontal cortex of patients with major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, MOOD CNS Program,Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Psychiat Serv, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 505 BP 155S EP 156S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301082 ER PT J AU Levitt, JJ Rosow, LK Connor, EE Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Levitt, JJ Rosow, LK Connor, EE Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI An MRI study of ventral and dorsal striatum in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, MRI Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, MRI Div, Brockton, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 520 BP 160S EP 160S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301097 ER PT J AU Adler, LE Cawthra, E Pincus, SS Woodward, L Wald, MC Staves, P House, R AF Adler, LE Cawthra, E Pincus, SS Woodward, L Wald, MC Staves, P House, R TI P50 gaiting: Differences between non combat-deployed and combat-deployed groups SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Denver VAMC, MIRECC, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Madigan Army Hosp, Tacoma, WA USA. Denver VA Med Ctr, MIRECC, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver Hlth Med Ctr, Dept Psychiat, Denver, CO 80202 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 559 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301136 ER PT J AU Goodman, M Flory, J Koenigsberg, H Siever, L New, A AF Goodman, M Flory, J Koenigsberg, H Siever, L New, A TI Aggressive responding in borderline personality disorder-baseline differences and treatment effects of a cognitive behavioral therapy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 564 BP 173S EP 173S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301141 ER PT J AU Salisbury, DF McCarley, RW AF Salisbury, DF McCarley, RW TI Differential effects of pitch and duration deviants on MMN in first hospitalized schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 582 BP 178S EP 179S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301159 ER PT J AU Salisbury, DF Niznikiewicz, M Spencer, K Mannan, R McCarley, RW AF Salisbury, DF Niznikiewicz, M Spencer, K Mannan, R McCarley, RW TI Binaural standard tones and dichotic deviants: Effects on MMN in schizophrenia and controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 581 BP 178S EP 178S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301158 ER PT J AU Bearden, CE Glahn, DC Caetano, SC Fonseca, M Olvera, RL Najt, P Hunter, K Pliszka, SR Soares, JC AF Bearden, CE Glahn, DC Caetano, SC Fonseca, M Olvera, RL Najt, P Hunter, K Pliszka, SR Soares, JC TI Deficits in working memory and executive function in juvenile bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Div Child & Adolescent Psychiat, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 616 BP 189S EP 189S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301188 ER PT J AU Greenberg, BD Gabriels, L Malone, DA Kubu, CS Malloy, PF Okun, MS Shapira, NA Friehs, GM Nuttin, B Rezai, AR Dougherty, DD Rauch, SL Goodman, WK Rasmussen, SA AF Greenberg, BD Gabriels, L Malone, DA Kubu, CS Malloy, PF Okun, MS Shapira, NA Friehs, GM Nuttin, B Rezai, AR Dougherty, DD Rauch, SL Goodman, WK Rasmussen, SA TI Deep brain stimulation (DBS) for OCD: Effects in multiple domains SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Butler Hosp, Brown Med Sch, Providence, RI 02906 USA. Univ Antwerp, B-2020 Antwerp, Belgium. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Florida, Gainesville, FL 32611 USA. Brown Med Sch, Providence, RI USA. Catholic Univ Louvain, B-3000 Louvain, Belgium. 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 646 BP 198S EP 198S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301218 ER PT J AU Koenigsberg, HW Prohovnik, I Fan, J Lee, H Osowsky, J New, A Goodman, M Guo, XD Pizzarello, S Siever, LJ AF Koenigsberg, HW Prohovnik, I Fan, J Lee, H Osowsky, J New, A Goodman, M Guo, XD Pizzarello, S Siever, LJ TI Patterns of neural activation during the processing of emotional pictures in affectively unstable borderline patients and normal controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. James J Peters VA Med Ctr, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 659 BP 201S EP 201S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301231 ER PT J AU Wirshing, WC Mahgerefteh, S Guzik, LH Boyd, JA Pierre, JM Wirshing, DA AF Wirshing, WC Mahgerefteh, S Guzik, LH Boyd, JA Pierre, JM Wirshing, DA TI Pharmacoeconomics: Divalproex sodium and schizophrenia spectrum disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 671 BP 205S EP 205S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301243 ER PT J AU Biederman, J AF Biederman, J TI Developmental trajectories of anxiety disorders in offspring at high risk for panic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 674 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301246 ER PT J AU Glahn, DC Bearden, CE Barrett, J Barguil, M Nery, FG Velligan, DI Soares, JC AF Glahn, DC Bearden, CE Barrett, J Barguil, M Nery, FG Velligan, DI Soares, JC TI Declarative memory impairment accentuated by history of psychosis in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 UTHSCSA, San Antonio, TX USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 675 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301247 ER PT J AU Mena, SJ Guzik, LH Mahgerefteh, S Pierre, JM Wirshing, DA Wirshing, WC AF Mena, SJ Guzik, LH Mahgerefteh, S Pierre, JM Wirshing, DA Wirshing, WC TI Aripiprazole: Effects on metabolic risk factors and sexual satisfaction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Greater Los Angeles Healthcare Ctr, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 676 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301248 ER PT J AU Caetano, SC Fonseca, M Chen, HH Nicoletti, M Stanley, JA Hatch, JP Olvera, RL Hunter, K Ortiz, O Pliszka, SR Soares, JC AF Caetano, SC Fonseca, M Chen, HH Nicoletti, M Stanley, JA Hatch, JP Olvera, RL Hunter, K Ortiz, O Pliszka, SR Soares, JC TI Proton chemical shift imaging in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, MOOD CNS Program, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Psychiat Serv, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat, BR-05508 Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Psychiat Res Unit, Sch Med, BR-90046900 Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78229 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Childl & Adolescent Psychiat, San Antonio, TX 78229 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 682 BP 208S EP 208S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301254 ER PT J AU Olvera, RL Caetano, SC Fonseca, M Nicoletti, M Stanley, JA Chen, HH Hatch, JP Hunter, K Pliszka, SR Soares, JC AF Olvera, RL Caetano, SC Fonseca, M Nicoletti, M Stanley, JA Chen, HH Hatch, JP Hunter, K Pliszka, SR Soares, JC TI N-acetyl aspartate reduction in the dorsolateral prefrontal cortex of pediatric bipolar patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 UTHSCSA, MOOD, CNS Program, Div Mood & Anxiety Disorders, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Res Unit, Porto Alegre, RS, Brazil. Wayne State Univ, Sch Med, Detroit, MI USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 729 BP 223S EP 223S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301301 ER PT J AU McClure, MM Romero, MJ Zegarelli, GL Harvey, PD Siever, LJ AF McClure, MM Romero, MJ Zegarelli, GL Harvey, PD Siever, LJ TI Visual learning and memory in schizotypal personality disorder: Evidence of unidimensional episodic memory deficits in the schizophrenia spectrum SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 James J Peters VAMC, VICN3 MIRECC, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 751 BP 229S EP 230S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301323 ER PT J AU Katsel, PL Davis, KL Haroutunian, V AF Katsel, PL Davis, KL Haroutunian, V TI Oligodendrocytes associated cell cycle gene expression abnormalities in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Mt Sinai Med Ctr, New York, NY 10029 USA. James J Peters Vet Affairs Med Ctr, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 771 BP 236S EP 236S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301343 ER PT J AU Dracheva, S Patel, N Woo, D Siever, LJ Haroutunian, V AF Dracheva, S Patel, N Woo, D Siever, LJ Haroutunian, V TI The role of the serotonin 2C receptor mRNA editing in suicidal behaviour SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 775 BP 237S EP 237S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301347 ER PT J AU Byne, W Dracheva, S Chu, THT AF Byne, W Dracheva, S Chu, THT TI Analysis of gene expression in the interstitial nuclei of the human anterior hypothalamus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 815 BP 249S EP 249S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301387 ER PT J AU Yao, JK Reddy, RD Keshavan, MS AF Yao, JK Reddy, RD Keshavan, MS TI Altered membrane lipids in first-episode psychoses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 61st Annual Convention of the Society-of-Biological-Psychiatry CY MAY 18-20, 2006 CL Toronto, CANADA SP Soc Biol Psychiat C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2006 VL 59 IS 8 SU S MA 822 BP 251S EP 251S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 032IE UT WOS:000236767301394 ER PT J AU Caetano, SC Kaur, S Brambilla, P Nicoletti, M Hatch, JP Sassi, RB Mallinger, AG Keshavan, MS Kupfer, DJ Frank, E Soares, JC AF Caetano, SC Kaur, S Brambilla, P Nicoletti, M Hatch, JP Sassi, RB Mallinger, AG Keshavan, MS Kupfer, DJ Frank, E Soares, JC TI Smaller cingulate volumes in unipolar depressed patients SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 59th Annual Meeting of the Society-of-Biological-Psychiatry CY APR 29-MAY 01, 2004 CL NEW YORK, NY SP Soc Biol Psychiat DE magnetic resonance imaging; cingulate; neuroimaging; depression; unipolar disorder; mood disorders ID SUBGENUAL PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; ANTERIOR CINGULATE; MAJOR DEPRESSION; MOOD DISORDERS; BIPOLAR-DISORDER; ABNORMALITIES; BRAIN; MRI; DEFICITS AB Background: The, anterior cingulate cortex is a key structure in brain networks involved in mood regulation. Abnormalities in this brain region are possibly implicated in the pathophysiology of depression. This anatomical magnetic resonance imaging (MRI) study compared cingulate cortex volumes in unipolar depressed patients and age- and gender-matched healthy control subjects. Methods: Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9 years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/- 10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of covariance with intracranial volume as the covariate. Results: The unipolar patients bad significantly smaller anterior and posterior cingulate volumes bilaterally compared with, healthy control subjects. When patients were divided into currently depressed (n = 27) and remitted (n = 10) subgroups. currently depressed patients bad significantly smaller anterior and Posterior cingulate volumes bilaterally compared with healthy control subjects, whereas remitted patients bad significantly smaller left anterior cingulate volumes compared with healthy individuals. Conclusions: Gray matter abnormalities in the cingulate cortex are implicated in the pathophysiology of unipolar depression. Smaller cingulate volumes in currently depressed patients support the hypothesis that cingulate cortex abnormalities are state dependent, whereas changes in left anterior cingulate might be trait related. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, I-33100 Udine, Italy. Univ Pittsburgh, Med Ctr, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010; Caetano, Sheila/H-5010-2012 OI brambilla, paolo/0000-0002-4021-8456; Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [RR 020571]; NIMH NIH HHS [MH 01736, MH 30915, MH 49115] NR 45 TC 84 Z9 93 U1 0 U2 11 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 APR 15 PY 2006 VL 59 IS 8 BP 702 EP 706 DI 10.1016/j.biopsych.2005.10.011 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 031HN UT WOS:000236695400005 PM 16414029 ER PT J AU Tanabe, J Tregellas, JR Martin, LF Freedman, R AF Tanabe, J Tregellas, JR Martin, LF Freedman, R TI Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE nicotine; smooth pursuit eye movement; schizophrenia; fMRI; hippocampus; cingulate ID CIGARETTE-SMOKING; ANTICIPATORY SACCADES; TRACKING DYSFUNCTION; BRAIN ACTIVATION; LEADING SACCADES; TOBACCO SMOKING; FMRI; PERFORMANCE; TASK; PARAHIPPOCAMPAL AB Background: Abnormal smooth pursuit eye movement (SPEM) in schizophrenic patients is a well known phenomenon, but the neurophysiological mechanisms underlying the deficit are unknown. Nicotine temporarily improves SPEM and has been associated with reduced hippocampal hemodynamic activity in schizophrenics. Nicotine's effect on brain activity in control subjects performing SPEM has not been studied. The purpose of this work was to determine if nicotine differentially affects brain activity in schizophrenic and control subjects during pursuit eye tracking. Methods: 16 subjects with schizophrenia and 16 control subjects underwent functional MR imaging during SPEM after receiving placebo or nicotine gum. Four brain regions were analyzed for main effects of group, drug, and interactions: hippocampus, cingulate gyrus, frontal eye fields, and area MT. Results: Nicotine reduced hippocampal activity in both groups, but the effect was greater in control subjects. A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activityin schizophrenic subjects. There were no significant effectsof group, drug, or interactions in frontal eye fields or area MT. Conclusion: Nicotine may improve SPEM performance in people with schizophrenia through cholinergic stimulation of the hippocampus and cingulate gyrus. Potential mechanisms include improved inhibitory function and attention. C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tanabe, J (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, Campus Box A034,4200 E 9th Ave, Denver, CO 80262 USA. EM jody.tanabe@uchsc.edu RI Tregellas, Jason/J-3637-2015 FU NIDA NIH HHS [K08DA1505] NR 57 TC 33 Z9 34 U1 2 U2 2 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 APR 15 PY 2006 VL 59 IS 8 BP 754 EP 761 DI 10.1016/j.biopsych.2005.09.004 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 031HN UT WOS:000236695400012 PM 16259965 ER PT J AU Mankad, A Taniguchi, T Cox, B Akkari, Y Rathbun, RK Lucas, L Bagby, G Olson, S D'Andrea, A Grompe, M AF Mankad, A Taniguchi, T Cox, B Akkari, Y Rathbun, RK Lucas, L Bagby, G Olson, S D'Andrea, A Grompe, M TI Natural gene therapy in monozygotic twins with Fanconi anemia SO BLOOD LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; HEMATOPOIETIC STEM-CELLS; X-INACTIVATION PATTERNS; IN-VIVO SELECTION; SOMATIC MOSAICISM; NUCLEAR-COMPLEX; GROUP C; REVERSE MOSAICISM; PROTEIN; FAA AB Monozygotic twin sisters, with nonhematologic symptoms of Fanconi anemia (FA), were discovered to be somatic mosaics for mutations in the FANCA gene. Skin fibroblasts, but not lymphocytes or committed hematopoietic progenitors, were sensitive to DNA cross-linking agents. Molecular analysis revealed, in skin cells of both twins, a frameshift causing deletion in exon 27 (2555 Delta T) and an exon 28 missense mutation (2670G > A/R880Q). The latter resulted in primarily cytoplasmic expression and reduced function of the mutant FANCA (R880Q) protein. Surprisingly, the same acquired exon 30 missense change (2927G > A/E966K) was detected in the hematopoietic cells of both sisters, but not in their fibroblasts, nor in either parent. This compensatory mutation existed in cis with the maternal exon 28 mutation, and it restored function and nuclear localization of the resulting protein. Both sisters have been free of hematologic symptoms for more than 2 decades, suggesting that this de novo mutation occurred prenatally in a single hematopoietic stem cell (HSC) in one twin and that descendants of this functionally corrected HSC, via intra-uterine circulation, repopulated the blood lineages of both sisters. This finding suggests that treating FA patients with gene therapy might require transduction of only a few hematopoietic stem cells. C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Grompe, M (reprint author), Oregon Hlth Sci Univ, Dept Mol & Med Genet, Mail Code L103,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM grompem@ohsu.edu OI Mankad, Anuj/0000-0001-6412-8060 FU NCI NIH HHS [P30 CA069533]; NHLBI NIH HHS [1P01 HL48546, P01 HL048546] NR 46 TC 36 Z9 36 U1 1 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 APR 15 PY 2006 VL 107 IS 8 BP 3084 EP 3090 DI 10.1182/blood-2005-07-2638 PG 7 WC Hematology SC Hematology GA 033FY UT WOS:000236833500021 PM 16397136 ER PT J AU Goldman, DC Berg, LK Heinrich, MC Christian, JL AF Goldman, DC Berg, LK Heinrich, MC Christian, JL TI Ectodermally derived steel/stem cell factor functions non-cell autonomously during primitive erythropoiesis in Xenopus SO BLOOD LA English DT Article ID C-KIT RECEPTOR; VENTRAL BLOOD ISLAND; EMBRYONIC BLOOD; EXPRESSION PATTERNS; HEMATOPOIETIC-CELLS; REGULATES LINEAGE; GASTRULA EMBRYO; SI-LOCUS; MESODERM; MOUSE AB Signals derived from nonhematopoietic tissues are essential for normal primitive erythropoiesis in vertebrates, but little is known about the nature of these signals. In Xenopus, unidentified factors secreted by ectodermal cells during gastrulation are required to enable the underlying ventral mesoderm to form blood. Steel is expressed in the ectoderm of early Xenopus embryos and is known to regulate definitive erythroid progenitor survival and differentiation in other organisms, making it an excellent candidate regula-tor of primitive erythropoiesis. In this study, we tested whether steel signaling is required for primitive red blood cell differentiation in mice and frogs. We show that Xsl is expressed in the ectoderm in Xenopus gastrulae and that c-kit homologs are expressed in the underlying mesoderm at the same stages of development. We present loss of function data in whole Xenopus embryos and explants that demonstrate a requirement for ectodermally derived steel to signal through c-kit in the mesoderm to support early steps in the differentiation of primitive erythroid but not myeloid cells. Finally, we show that primitive erythropoiesis is not disrupted in mouse embryos that lack c-kit function. Our data suggest a previously unrecognized and unique function of steel/c-kit during primitive erythropoiesis in Xenopus. C1 Oregon Hlth Sci Univ, Dept Dev & Cell Biol, Div Hematol & Oncol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Div Hematol & Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Christian, JL (reprint author), Oregon Hlth Sci Univ, Dept Dev & Cell Biol, Div Hematol & Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM christia@ohsu.edu FU NICHD NIH HHS [R03 HD050242] NR 62 TC 6 Z9 6 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 APR 15 PY 2006 VL 107 IS 8 BP 3114 EP 3121 DI 10.1182/blood-2005-093930 PG 8 WC Hematology SC Hematology GA 033FY UT WOS:000236833500025 PM 16357321 ER PT J AU Duda, DG AF Duda, DG TI Antiangiogenesis and drug delivery to tumors: Bench to bedside and back SO CANCER RESEARCH LA English DT Article ID RECTAL-CANCER PATIENTS; ENDOTHELIAL-CELLS; PROGENITOR CELLS; CLINICAL-TRIALS; THERAPY; NORMALIZATION; PERMEABILITY; CHEMOTHERAPY; VASCULATURE; EXPRESSION AB After over 30 years of preclinical and clinical development, antiangiogenic agents have recently entered the clinic as attractive targeted therapeutics for the treatment of cancer. Fueled by exciting new developments in the field, the AACR Special Conference was designed to broadly survey critical scientific advances in the antiangiogenic therapy of cancer. Because these advances have come primarily with the use of combinations of antiangiogenic agents with chemotherapy, or with antiangiogenic agents that also directly target the cancer cells, the central theme included the issue of drug delivery to tumors. These two major issues were addressed in concert, from basic mechanisms of action of antiangiogenic agents to new combination approaches to cancer treatment. Nearly 300 participants from 20 countries registered for the conference, drawn both from academia and industry, with a wide range in experience and background. Dr. Rakesh Jain, along with conference co-chairs, Drs. Lee Ellis and Luisa Iruela-Arispe, assembled an outstanding lineup of speakers for this conference that included many of the pioneers in the fields of angiogenesis and drug delivery from the U.S. and abroad. This resulted in an excellent overview of the advances in our understanding of cellular and molecular aspects of tumor angiogenesis and antiangiogenic therapy of cancer in combination with conventional therapy. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Duda, DG (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Steele Lab Tumor Biol, Cox-734,100 Blossom St, Boston, MA 02114 USA. EM duda@steele.mgh.harvard.edu NR 32 TC 6 Z9 7 U1 0 U2 1 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 APR 15 PY 2006 VL 66 IS 8 BP 3967 EP 3970 DI 10.1158/0008-5472.CAN-05-4536 PG 4 WC Oncology SC Oncology GA 033JM UT WOS:000236843200003 PM 16618712 ER PT J AU Xu, L Cochran, DM Tong, RT Winkler, F Kashiwagi, S Jain, RK Fukumura, D AF Xu, L Cochran, DM Tong, RT Winkler, F Kashiwagi, S Jain, RK Fukumura, D TI Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and metastasis by depleting vascular endothelial growth factor homodimers in orthotopic mouse models SO CANCER RESEARCH LA English DT Article ID VEGF-INDUCED ANGIOGENESIS; PERMEABILITY FACTOR; MICROVASCULAR PERMEABILITY; PATHOLOGICAL CONDITIONS; CELLS; MICE; CANCER; EXPRESSION; MECHANISM; MIGRATION AB The role of placenta growth factor (PIGF) in pathologic angiogenesis is controversial. The effects of PlGF on growth, angiogenesis, and metastasis from orthotopic tumors are not known. To this end, we stably transfected three human cancer cell lines (A549 lung, HCT116 colon, and U87-MG glioblastoma) with human plgf-2 full-length cDNA. Overexpression of PlGF did not affect tumor cell proliferation or migration in vitro. The growth of PIGF-overexpressing tumors grown orthotopically or ectopically was impaired in all three tumor models. This decrease in tumor growth correlated with a decrease in tumor angiogenesis. The PIGF-overexpressing tumors had decreased vessel density and increased vessel diameter, but vessel permeability was not different from the parental tumors. Tumors overexpressing PlGF exhibited higher levels of PlGF homodimers and PIGF/vascular endothelial growth factor (VEGF) heterodimers but decreased levels of VEGF homodimers. Our study shows that PlGF overexpression decreases VEGF homodimer formation and inhibits tumor progression. C1 Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Xu, L (reprint author), Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, 100 Blossom St,Cox-7, Boston, MA 02114 USA. EM lei@steele.mgh.harvard.edu FU NCI NIH HHS [P01-CA80124] NR 28 TC 52 Z9 55 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 APR 15 PY 2006 VL 66 IS 8 BP 3971 EP 3977 DI 10.1158/0008-5472.CAN-04-3085 PG 7 WC Oncology SC Oncology GA 033JM UT WOS:000236843200004 PM 16618713 ER PT J AU Hunter, C Smith, R Cahill, DP Stephens, P Stevens, C Teague, J Greenman, C Edkins, S Bignell, G Davies, H O'Meara, S Parker, A Avis, T Barthorpe, S Brackenbury, L Buck, G Butler, A Clements, J Cole, J Dicks, E Forbes, S Gorton, M Gray, K Halliday, K Harrison, R Hills, K Hinton, J Jenkinson, A Jones, D Kosmidou, V Laman, R Lugg, R Menzies, A Perry, J Petty, R Raine, K Richardson, D Shepherd, R Small, A Solomon, H Tofts, C Varian, J West, S Widaa, S Yates, A Easton, DF Riggins, G Roy, JE Levine, KK Mueller, W Batchelor, TT Louis, DN Stratton, MR Futreal, PA Wooster, R AF Hunter, C Smith, R Cahill, DP Stephens, P Stevens, C Teague, J Greenman, C Edkins, S Bignell, G Davies, H O'Meara, S Parker, A Avis, T Barthorpe, S Brackenbury, L Buck, G Butler, A Clements, J Cole, J Dicks, E Forbes, S Gorton, M Gray, K Halliday, K Harrison, R Hills, K Hinton, J Jenkinson, A Jones, D Kosmidou, V Laman, R Lugg, R Menzies, A Perry, J Petty, R Raine, K Richardson, D Shepherd, R Small, A Solomon, H Tofts, C Varian, J West, S Widaa, S Yates, A Easton, DF Riggins, G Roy, JE Levine, KK Mueller, W Batchelor, TT Louis, DN Stratton, MR Futreal, PA Wooster, R TI A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy SO CANCER RESEARCH LA English DT Article ID KINASE GENE FAMILY; DNA MISMATCH REPAIR; HUMAN-CELLS; CANCER; GLIOBLASTOMA; TEMOZOLOMIDE; SPECTRA; AGENTS AB Malignant gliomas have a very poor prognosis. The current standard of care for these cancers consists of extended adjuvant treatment with the alkylating agent temozolomide after surgical resection and radiotherapy. Although a statistically significant increase in survival has been reported with this regimen, nearly all gliomas recur and become insensitive to further treatment with this class of agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of 518 protein kinases in each of nine gliomas. Large numbers of somatic mutations were observed in two gliomas recurrent after alkylating agent treatment. The pattern of mutations in these cases showed strong similarity to that induced by alkylating agents in experimental systems. Further investigation revealed inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We propose that inactivating somatic mutations of MSH6 confer resistance to alkylating agents in gliomas in vivo and concurrently unleash accelerated mutagenesis in resistant clones as a consequence of continued exposure to alkylating agents in the presence of defective mismatch repair. The evidence therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents convert from induction of tumor cell death to promotion of neoplastic progression. These observations highlight the potential of large scale sequencing for revealing and elucidating mutagenic processes operative in individual human cancers. C1 Wellcome Trist Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. Massachusetts Gen Hosp, Mol Pathol Unit, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Cambridge, Canc Res UK Epidemiol Unit, Cambridge, England. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Inst Canc Res, Sutton, Surrey, England. RP Futreal, PA (reprint author), Wellcome Trist Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, England. EM paf@sanger.ac.uk OI Jenkinson, Andrew/0000-0002-0703-6984; Yates, Andrew/0000-0002-8886-4772; Gray, Kristian/0000-0002-7035-7107; Hunter, Christopher/0000-0002-1335-0881; Richardson, David/0000-0003-0247-9118 FU Wellcome Trust NR 21 TC 153 Z9 158 U1 1 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 APR 15 PY 2006 VL 66 IS 8 BP 3987 EP 3991 DI 10.1158/0008-5472.CAN-06-0127 PG 5 WC Oncology SC Oncology GA 033JM UT WOS:000236843200007 PM 16618716 ER PT J AU Yao, J Weremowicz, S Feng, B Gentleman, RC Marks, JR Gelman, R Brennan, C Polyak, K AF Yao, J Weremowicz, S Feng, B Gentleman, RC Marks, JR Gelman, R Brennan, C Polyak, K TI Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression SO CANCER RESEARCH LA English DT Article ID COPY-NUMBER; PIK3CA GENE; SPORADIC BREAST; PROSTATE-CANCER; OVARIAN-CANCER; HIGH-FREQUENCY; BRCA2 PATHWAY; TEL GENE; IN-SITU; AMPLIFICATION AB To identify genetic changes involved in the progression of breast carcinoma, we did cDNA array comparative genomic hybridization (CGH) on a panel of breast tumors, including 10 ductal carcinoma in situ (DCIS), 18 invasive breast carcinomas, and two lymph node metastases. We identified 49 minimal commonly amplified regions (MCRs) that included known (1q, 8q24, 11q13, 17q21-q23, and 20q13) and several uncharacterized (12p13 and 16p13) regional copy number gains. With the exception of the 17q21 (ERBB2) amplicon, the overall frequency of copy number alterations was higher in invasive tumors than that in DClS, with several of them present only in invasive cancer. Amplification of candidate loci was confirmed by quantitative PCR in breast carcinomas and cell lines. To identify putative targets of. amplicons, we developed a method combining array CGH and serial analysis of gene expression (SAGE) data to correlate copy number and expression levels for each gene within Wits. Using this approach, we were able to distinguish a few candidate targets from a set of coamplified genes. Analysis of the 12p13-p12 amplicon identified four putative targets: TEL/ETV6, H2AFJ, EPS8, and KRAS2. The amplification of all four candidates was confirmed by quantitative PCR and fluorescence in situ hybridization, but only H2AFJ and EPS8 were overexpressed in breast tumors with 12p13 amplification compared with a panel of normal mammary epithelial cells. These results show the power of combined array CGH and SAGE analysis for the identification of candidate amplicon targets and identify H2AFJ and EPS8 as novel putative oncogenes in breast cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D740C,44 Binney St D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [CA89393, CA93683] NR 55 TC 106 Z9 111 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2006 VL 66 IS 8 BP 4065 EP 4078 DI 10.1158/0008-5472.CAN-05-4083 PG 14 WC Oncology SC Oncology GA 033JM UT WOS:000236843200017 PM 16618726 ER PT J AU Heltweg, B Gatbonton, T Schuler, AD Posakony, J Li, HZ Goehle, S Kollipara, R DePinho, RA Gu, YS Simon, JA Bedalov, A AF Heltweg, B Gatbonton, T Schuler, AD Posakony, J Li, HZ Goehle, S Kollipara, R DePinho, RA Gu, YS Simon, JA Bedalov, A TI Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes SO CANCER RESEARCH LA English DT Article ID CENTER B-CELLS; HISTONE DEACETYLASE; SIRT1 DEACETYLASE; DEPSIPEPTIDE FR901228; ACETYLATION; P53; BCL6; IDENTIFICATION; TRANSCRIPTION; ACTIVATION AB SIRT1 and other NAD-dependent deacetylases have been implicated in control of cellular responses to stress and in tumorigenesis through deacetylation of important regulatory proteins, including p53 and the BCL6 oncoprotein. Hereby, we describe the identification of a compound we named cambinol that inhibits NAD-dependent deacetylase activity of human SIRT1 and SIRT2. Consistent with the role of SIRT1 in promoting cell survival during stress, inhibition of SIRT1 activity with cambinol during genotoxic stress leads to hyperacetylation of key stress response proteins and promotes cell cycle arrest. Treatment of BCL6-expressing Burkitt lymphoma cells with cambinol as a single agent induced apoptosis, which was accompanied by hyperacetylation of BCL6 and p53. Because acetylation inactivates BCL6 and has the opposite effect on the function of p53 and other checkpoint pathways, the antitumor activity of cambinol in Burkitt lymphoma cells may be accomplished through a combined effect of BCL6 inactivation and checkpoint activation. Cambinol was well tolerated in mice and inhibited growth of Burkitt lymphoma xenografts. Inhibitors of NAD-dependent deacetylases may constitute novel anticancer agents. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Radiat Oncol & Immunol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Bedalov, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, D2-100,1100 Fairview Ave N, Seattle, WA 98109 USA. EM abedalov@fhcrc.org FU NCI NIH HHS [CA78746]; NHLBI NIH HHS [HL04211]; NIDDK NIH HHS [DK56465] NR 56 TC 293 Z9 308 U1 0 U2 24 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 APR 15 PY 2006 VL 66 IS 8 BP 4368 EP 4377 DI 10.1158/0008-5472.CAN-05-3617 PG 10 WC Oncology SC Oncology GA 033JM UT WOS:000236843200053 PM 16618762 ER PT J AU Pardee, AB AF Pardee, AB TI Regulatory molecular biology SO CELL CYCLE LA English DT Review DE molecular biology; feedback control; cell cycle; apoptosis; cancer; regulation; repression; allosteric ID CELL-DIVISION CYCLE; ESCHERICHIA-COLI; ALLOSTERIC REGULATION; FEEDBACK INHIBITION; PROTEIN-DEGRADATION; RESTRICTION POINT; GENETIC-CONTROL; BETA-LAPACHONE; MECHANISM; CANCER AB Close regulations of molecular biological processes are essential for life. Defective controls cause diseases such as cancer and neurological malfunctions. We now are provided with a plethora of regulatory mechanisms exerted at many levels. Prominent are covalent protein modifications, non-covalent feedback inhibition that modifies enzyme activity, and enzyme induction. Non-covalent or covalent binding to them of either small molecules or proteins act on functional DNA, RNA, proteins and metabolites regulates their production and degradation rates, activities and intra-cell locations. Time frames differ greatly, from seconds to days or longer. A control at every level is balanced by an opposing mechanism: populations of organisms are balanced by birth vs. death, cell synthesis by apoptosis, mutation by DNA repair, macromolecular syntheses by their degradations, metabolite anabolism vs. catabolism, enzyme activation by inhibition, protein kinases by phosphatases. Any abnormal molecular condition is sensed when regulation is defective as in cancer, which leads to its rectification, to cell death, or to disease if this is not possible. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM arthur_pardee@dfci.harvard.edu NR 87 TC 7 Z9 7 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 15 PY 2006 VL 5 IS 8 BP 846 EP 852 DI 10.4161/cc.5.8.2634 PG 7 WC Cell Biology SC Cell Biology GA 057DB UT WOS:000238575100012 PM 16552190 ER PT J AU Esposito, V Palescandolo, E Spugnini, EP Montesarchio, V De Luca, A Cardillo, I Cortese, G Baldi, A Chirianni, A AF Esposito, V Palescandolo, E Spugnini, EP Montesarchio, V De Luca, A Cardillo, I Cortese, G Baldi, A Chirianni, A TI Evaluation of antitumoral properties of the protease inhibitor indinavir in a murine model of hepatocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID HIV-INFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; KAPOSIS-SARCOMA; ANTIRETROVIRAL THERAPY; GROWTH-FACTOR; MATRIX METALLOPROTEINASES; CANCER METASTASIS; HEPATITIS-C; ANGIOGENESIS; CELLS AB Purpose: Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/ hepatitis C virus (HCV)-coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. Experimental Design: We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. Results: We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase - mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors. Conclusion: Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV-coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications. C1 Third Div Cotugno Hosp, Naples, Italy. Univ Naples 2, Dept Med & Publ Hlth, Sect Clin Anat, Naples, Italy. Univ Naples 2, Dept Biochem, Sect Pathol, Naples, Italy. Int Soc Study Comparat Oncol, Silver Spring, MD USA. Regina Elena Inst Canc Res, SAFU Dept, Rome, Italy. Regina Elena Inst Canc Res, Dept Dev Therapeut Programs, Lab D, Rome, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Esposito, V (reprint author), T Tasso 169-C, I-80127 Naples, Italy. EM esposvin@libero.it OI Baldi, Alfonso/0000-0002-8693-3842 NR 32 TC 23 Z9 23 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 APR 15 PY 2006 VL 12 IS 8 BP 2634 EP 2639 DI 10.1158/1078-0432.CCR-05-2188 PG 6 WC Oncology SC Oncology GA 037UR UT WOS:000237173300036 PM 16638877 ER PT J AU Vrailas, AD Marenda, DR Cook, SE Powers, MA Lorenzen, JA Perkins, LA Moses, K AF Vrailas, AD Marenda, DR Cook, SE Powers, MA Lorenzen, JA Perkins, LA Moses, K TI Smoothened and thickveins regulate moleskin/importin 7-mediated MAP kinase signaling in the developing Drosophila eye SO DEVELOPMENT LA English DT Article DE Drosophila; Moleskin; Importin 7; morphogenetic furrow; MAP kinase; cell cycle; nuclear translocation; ERK; Hedgehog; Dpp; Egfr ID SENSORY ORGAN DEVELOPMENT; EGF RECEPTOR; PATTERN-FORMATION; PRONEURAL GENE; MORPHOGENETIC FURROW; COMPOUND EYE; CELL-FATE; PHOTORECEPTOR CELLS; OMMATIDIAL ROTATION; PLANAR POLARITY AB The Drosophila Mitogen Activated Protein Kinase ( MAPK) Rolled is a key regulator of developmental signaling, relaying information from the cytoplasm into the nucleus. Cytoplasmic MEK phosphorylates MAPK (pMAPK), which then dimerizes and translocates to the nucleus where it regulates transcription factors. In cell culture, MAPK nuclear translocation directly follows phosphorylation, but in developing tissues pMAPK can be held in the cytoplasm for extended periods ( hours). Here, we show that Moleskin antigen ( Drosophila Importin 7/Msk), a MAPK transport factor, is sequestered apically at a time when lateral inhibition is required for patterning in the developing eye. We suggest that this apical restriction of Msk limits MAPK nuclear translocation and blocks Ras pathway nuclear signaling. Ectopic expression of Msk overcomes this block and disrupts patterning. Additionally, the MAPK cytoplasmic hold is genetically dependent on the presence of Decapentaplegic (Dpp) and Hedgehog receptors. C1 Emory Univ, Sch Med, Dept Cell Biol, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. Med Coll Wisconsin, Dept Pediat Gastroenterol, Milwaukee, WI 53226 USA. RP Moses, K (reprint author), Howard Hughes Med Inst, Janelia Farm Res Campus, Ashburn, VA 20147 USA. EM mosesk@hhmi.org FU NEI NIH HHS [R01 EY12537, R01 EY012537]; NICHD NIH HHS [P01 HD39942, P01 HD039942]; NIGMS NIH HHS [1 F32 GM073608, R01 GM061707, R01 GM61707, T32 GM008490, F32 GM073608-01A1, F32 GM073608] NR 84 TC 20 Z9 20 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 15 PY 2006 VL 133 IS 8 BP 1485 EP 1494 DI 10.1242/dev.02334 PG 10 WC Developmental Biology SC Developmental Biology GA 032WM UT WOS:000236806900008 PM 16540506 ER PT J AU Yang, L Cai, CL Lin, LZ Qyang, YB Chung, C Monteiro, RM Mummery, CL Fishman, GI Cogen, A Evans, S AF Yang, L Cai, CL Lin, LZ Qyang, YB Chung, C Monteiro, RM Mummery, CL Fishman, GI Cogen, A Evans, S TI Isl1Cre reveals a common Bmp pathway in heart and limb development SO DEVELOPMENT LA English DT Article DE Isl1; Bmp; Tbx2; Tbx3; heart; hindlimb ID APICAL ECTODERMAL RIDGE; ULNAR-MAMMARY SYNDROME; HOLT-ORAM-SYNDROME; FUNCTIONAL-CHARACTERIZATION; CONDUCTION SYSTEM; OUTFLOW-TRACT; HAND SYNDROME; MOUSE LIMB; GENE; EXPRESSION AB A number of human congenital disorders present with both heart and limb defects, consistent with common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset of cardiac progenitors. Here, we perform lineage studies with an Isl1Cre mouse line to demonstrate that Isl1 also marks a subset of limb progenitors. In both cardiac and limb progenitors, Isl1 expression is downregulated as progenitors migrate in to form either heart or limb. To investigate common heart-limb pathways in Isl1-expressing progenitors, we ablated the Type I Bmp receptor, Bmpr1a utilizing Isl1Cre/+. Analysis of consequent heart and limb phenotypes has revealed novel requirements for Bmp signaling. Additionally, we find that Bmp signaling in Isl1-expressing progenitors is required for expression of T-box transcription factors Tbx2 and Tbx3 in heart and limb. Tbx3 is required for heart and limb formation, and is mutated in ulnar-mammary syndrome. We provide evidence that the Tbx3 promoter is directly regulated by Bmp Smads in vivo. C1 Univ Calif San Diego, Skaggs Sch Pharm, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands. NYU, Sch Med, Leon H Charney Div Cardiol, New York, NY 10016 USA. RP Evans, S (reprint author), Univ Calif San Diego, Skaggs Sch Pharm, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM syevans@ucsd.edu RI Monteiro, Rui/J-2544-2013; Yang, Lei/D-7462-2015; Evans, Sylvia/G-1980-2015 OI Monteiro, Rui/0000-0002-4223-8506; FU NHLBI NIH HHS [R01 HL074066, R01 HL070867] NR 54 TC 122 Z9 125 U1 0 U2 12 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 APR 15 PY 2006 VL 133 IS 8 BP 1575 EP 1585 DI 10.1242/dev.02322 PG 11 WC Developmental Biology SC Developmental Biology GA 032WM UT WOS:000236806900016 PM 16556916 ER PT J AU Davidson, AJ Zon, LI AF Davidson, AJ Zon, LI TI The caudal-related homeobox genes cdx1a and cdx4 act redundantly to regulate hox gene expression and the formation of putative hematopoietic stem cells during zebrafish embryogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE cdx; caudal homeobox; hox; zebrafish; hematopoicsis; hematopoietic stem cells ID ANTERIOR-POSTERIOR AXIS; ACUTE MYELOID-LEUKEMIA; DEFINITIVE HEMATOPOIESIS; VERTEBRATE DEVELOPMENT; PROGENITORS; EMBRYOS; XENOPUS; GASTRULATION; GRADIENT; HOMOLOG AB The hox genes play a central role in organogenesis and are implicated in the fort-nation of hematopoietic stern cells (HSCs). The cdx genes encode homeodomain transcription factors that act as master regulators of the hox genes. In zebrafish, mutations in cdx4 cause a severe, but not complete, deficit in embryonic blood cells. Here, we report the expression and function of cdx1a, a zebrafish Cdx1 paralogue. Using morpholino-mediated knockdown of cdx1a in a cdx4 mutant background, we show that a deficiency in both cdx genes causes a severe perturbation of hox gene expression and a complete failure to specify blood. The hematopoietic defect in cdx-deficient embryos does not result from a general block in posterior mesoderm differentiation as endothelial cells and kidney progenitors are still formed in the doubly deficient embryos. In addition, cdx-deficient embryos display a significant reduction in runx1a(+) putative HSCs in the zebrafish equivalent to the aorta-gonad-mesonephros (AGM) region. Overexpressing hoxa9a in cdx-deficient embryos rescues embryonic erythropoiesis in the posterior mesoderm as well as the formation of HSCs in the AGM region. Taken together, these results suggest that the cdx-hox pathway plays an essential role in the formation of both embryonic erythroid cells and definitive HSCs during vertebrate embryogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Karp Bldg 7,1 Blackfan Circle, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 60 TC 70 Z9 72 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2006 VL 292 IS 2 BP 506 EP 518 DI 10.1016/j.ydbio.2006.01.003 PG 13 WC Developmental Biology SC Developmental Biology GA 034RI UT WOS:000236947900018 PM 16457800 ER PT J AU Fieber, CB Eldridge, J Taha, TA Obeid, LM Muise-Helmericks, RC AF Fieber, CB Eldridge, J Taha, TA Obeid, LM Muise-Helmericks, RC TI Modulation of total Akt kinase by increased expression of a single isoform: Requirement of the sphingosine-1-phosphate receptor, Edg3/S1P3, for the VEGF-dependent expression of Akt3 in primary endothelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-COUPLED RECEPTORS; NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR; SPHINGOSINE 1-PHOSPHATE; SIGNAL-TRANSDUCTION; PHOSPHOINOSITIDE 3-KINASE; CANCER-CELLS; PATHWAY; SURVIVAL; APOPTOSIS AB Akt kinase is an important downstream effector of VEGF in primary endothelial cells (EC), promoting angiogenesis by increased cellular survival, motility and tubulogenesis. Akt1 is the founding member of a family of serine threonine kinases thought to have overlapping function. We sought to determine if other Akt family members were also regulated by VEGF in EC. We show that treatment of EC with the angiogenic inducers VEGF or sphingosine-1-phosphate (SIP) results in an increased stabilization of Akt3 mRNA, concur-rent with a PI3 kinase-dependent, Akt1-independent increase in both the protein and its phosphorylation. Given the similarity of Akt3 regulation by VEGF and S1P, the sensitivity of VEGF stimulation to the Gi-protein uncoupling reagent, pertussis toxin was tested and shows that VEGF stimulation requires Gi-protein signaling. We show that the VEGF stimulates the expression of Edg3/S1P3 (S1P3) and that expression of this Gi-protein-coupled receptor is both sufficient and necessary for the expression of Akt3. Blockade of a single isoform. does not overtly affect cellular function, whereas inhibition of both kinases results in an increase in apoptosis and a down-regulation of cyclin D3. These results suggest a model whereby extracellular cues maintain total Akt kinase levels through the regulation of specific isoform expression providing a fail-safe mechanism to maintain necessary levels of Akt kinase activity. (c) 2006 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. RP Muise-Helmericks, RC (reprint author), Univ S Carolina, Hollings Canc Ctr, Rm 320,86 Jonathan Lucas St, Charleston, SC 29403 USA. EM musehelm@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01CA097132]; NCRR NIH HHS [P20 RR16434] NR 49 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 15 PY 2006 VL 312 IS 7 BP 1164 EP 1173 DI 10.1016/j.yexcr.2006.01.022 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 031UE UT WOS:000236728900019 PM 16527273 ER PT J AU Nguyen, BC Lefort, K Mandinova, A Antonini, D Devgan, V Della Gatta, G Koster, MI Zhang, Z Wang, J di Vignano, AT Kitajewski, J Chiorino, G Roop, DR Missero, C Dotto, GP AF Nguyen, BC Lefort, K Mandinova, A Antonini, D Devgan, V Della Gatta, G Koster, MI Zhang, Z Wang, J di Vignano, AT Kitajewski, J Chiorino, G Roop, DR Missero, C Dotto, GP TI Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation SO GENES & DEVELOPMENT LA English DT Article DE keratinocyte; stem cells; Notch; p63; interferon -responsive genes; HES/HERP family members ID NF-KAPPA-B; NEGATIVE TRANSCRIPTIONAL REGULATOR; STEM-CELL; SIGNALING PATHWAYS; INCREASED APOPTOSIS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; TARGET GENES; P53 HOMOLOG; GROWTH AB Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch 1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Telethon Inst Genet & Med, TIGEM, I-80131 Naples, Italy. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Columbia Univ, Med Ctr, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Obstet & Gynecol, New York, NY 10032 USA. Columbia Univ, Med Ctr, Irving Canc Res Ctr, New York, NY 10032 USA. Fondo Edo Tempia, Lab Pharmacogen, I-13900 Biella, Italy. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM missero@tigem.it; gdotto@partners.org RI Zhang, Zhuo/B-8601-2012; Chiorino, Giovanna/K-5037-2016; OI Chiorino, Giovanna/0000-0002-9502-6400; Missero, Caterina/0000-0003-0905-5123 FU NCI NIH HHS [CA16038, CA73796, P01 CA016038, R01 CA073796]; NIAMS NIH HHS [AR39190, R01 AR039190]; Telethon [TGM03P14, TGM06S01] NR 81 TC 219 Z9 224 U1 2 U2 13 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 APR 15 PY 2006 VL 20 IS 8 BP 1028 EP 1042 DI 10.1101/gad.1406006 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 034SS UT WOS:000236951500012 PM 16618808 ER PT J AU Kock, N Naismith, TV Boston, HE Ozelius, LJ Corey, DP Breakefield, XO Hanson, PI AF Kock, N Naismith, TV Boston, HE Ozelius, LJ Corey, DP Breakefield, XO Hanson, PI TI Effects of genetic variations in the dystonia protein torsinA: identification of polymorphism at residue 216 as protein modifier SO HUMAN MOLECULAR GENETICS LA English DT Article ID EARLY-ONSET DYSTONIA; TOR1A DYT1 GENE; NUCLEAR-ENVELOPE; CAENORHABDITIS-ELEGANS; MUTANT TORSINA; PC12 CELLS; PACKAGING SYSTEM; ATPASES; MUTATIONS; STRESS AB Four naturally occurring sequence variations have been found in the coding region of the DYT1 gene encoding torsinA. One of these, a 3 bp (Delta GAG) deletion, underlies dominantly inherited cases of early-onset torsion dystonia. Others, including a single nucleotide polymorphism that replaces aspartic acid (D) at residue 216 with histidine (H) in 12% of normal alleles and two other rare deletions, have not been clearly associated with disease. To gain insight into how these sequence variations affect torsinA, we used the structure of the related protein ClpB to provide a model of torsinA's AAA+ domain. Motifs important for ATP hydrolysis-sensor 1 and sensor 2-were identified, mutagenized and used to validate predictions of this model. Inspection revealed that the Delta GAG deletion associated with dystonia removes one residue from an alpha-helix in the C-terminal portion of the AAA+ domain. The resulting distortion in torsinA structure may underlie this mutant's known tendency to produce ER-derived inclusions as well as its proposed loss of function. The D/H polymorphism at residue 216 falls in the N-terminal portion of the AAA+ domain near the sensor 1 motif. Surprisingly, cells expressing torsinA with the polymorphic histidine developed inclusions similar to those associated with Delta GAG-torsinA, indicating that this change may also affect torsinA structure. Introducing H216 into Delta GAG-torsinA reduced its tendency to form inclusions, suggesting that the two changes offset each other. Our findings point to a structural basis for the defects associated with the disease-linked Delta GAG deletion in torsinA. They also suggest possible connections between the allelic polymorphism at residue 216 and the penetrance of DYT1 dystonia, as well as a possible role for this polymorphism in related disease states. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Lubeck, Dept Neurol, Lubeck, Germany. RP Hanson, PI (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, 660 S Euclid,Campus Box 8228, St Louis, MO 63110 USA. EM phanson22@wustl.edu RI Hanson, Phyllis/E-9420-2012; OI Corey, David/0000-0003-4497-6016 FU NINDS NIH HHS [NS 28384, NS 050717, NS 37409] NR 57 TC 65 Z9 65 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2006 VL 15 IS 8 BP 1355 EP 1364 DI 10.1093/hmg/ddl055 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 030DK UT WOS:000236613300011 PM 16537570 ER PT J AU Temple, G Lamesch, P Milstein, S Hill, DE Wagner, L Moore, T Vidal, M AF Temple, G Lamesch, P Milstein, S Hill, DE Wagner, L Moore, T Vidal, M TI From genome to proteome: developing expression clone resources for the human genome SO HUMAN MOLECULAR GENETICS LA English DT Review ID SITE-SPECIFIC RECOMBINATION; LENGTH CDNA LIBRARIES; OLIGO-CAPPING METHOD; MESSENGER-RNA; INTERACTION NETWORK; FUNCTIONAL PROTEOMICS; RAPID CONSTRUCTION; ISOFORM DIVERSITY; GENETIC SYSTEM; LARGE NUMBERS AB cDNA clones have long been valuable reagents for studying the structure and function of proteins. With recent access to the entire human genome sequence, it has become possible and highly productive to compare the sequences of mRNAs to their genes, in order to validate the sequences and protein-coding annotations of each (1,2). Thus, well-characterized collections of human cDNAs are now playing an essential role in defining the structure and function of human genes and proteins. In this review, we will summarize the major collections of human cDNA clones, discuss some limitations common to most of these collections and describe several noteworthy proteomics applications, focusing on the detection and analysis of protein-protein interactions (PPI). These human cDNA collections contain principally two types of cDNA clones. The largest collections comprise cDNAs with full-length protein coding sequences (FL-CDS). Some but not all of these cDNA clones may represent the entire mRNA sequence, but many are missing considerable non-coding UTR sequence, usually at the 5' end. A second type of cDNA clone, a 'full-ORF' (F-ORF) expression clone, is one where the annotated protein-coding sequence, excised of 5' UTR and 3' UTR sequence, has been transferred to a vector designed to facilitate transfer to other vectors for protein expression. C1 NHGRI, Mammalian Gene Collect, NIH, Bethesda, MD 20892 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CCSB, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Fac Univ Notre Dame Paix, Unite Rech & Biol Mol, B-5000 Namur, Belgium. Open Biosyst, Huntsville, AL 35806 USA. RP Temple, G (reprint author), NHGRI, Mammalian Gene Collect, NIH, Bethesda, MD 20892 USA. EM gtemple@mail.nih.gov RI Hill, David/B-6617-2011 NR 89 TC 22 Z9 24 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 15 PY 2006 VL 15 SI 1 BP R31 EP R43 DI 10.1093/hmg/ddl048 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 039QE UT WOS:000237320500004 PM 16651367 ER PT J AU Kusano, AS Trichopoulos, D Terry, KL Chen, WY Willett, WC Michels, KB AF Kusano, AS Trichopoulos, D Terry, KL Chen, WY Willett, WC Michels, KB TI A prospective study of breast size and premenopausal breast cancer incidence SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID PARENCHYMAL PATTERNS; ADIPOSE-TISSUE; UNITED-STATES; RISK-FACTORS; ETIOLOGY; AUGMENTATION; EPIDEMIOLOGY; WOMEN AB Studies of the association between breast size, as a proxy for mammary gland mass, and breast cancer risk have given equivocal results. Most have been case-control studies with limited statistical power. We conducted a prospective analysis of the relation between breast size as measured by self-reported bra cup size and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Bra cup size at age 20 was assessed among 89,268 premenopausal women aged 29-47 in 1993. Subsequent incident cases of invasive breast cancer were assessed until 2001. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a Cox proportional hazards model adjusting for potential confounders and risk factors for breast cancer. During 622,732 person-years of follow-up, 803 premenopausal women were newly diagnosed with invasive breast cancer. For women with a BMI below 25 kg/m(2), those with a bra cup size of "D or larger" had a significantly higher incidence of breast cancer than women who reported "A or smaller" (covariate adjusted HR = 1.80; 95% CI 1.13-2.88; P-trend = 0.01). There was no significant association among women with a BMI of 25 kg/m2 or higher. Stratifying by BMI at age 18 at a cutoff point of 21 kg/m(2) gave similar results. Larger bra cup size at a young age is associated with a higher incidence of premenopausal breast cancer, though this association is limited to leaner women. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. RP Michels, KB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM kmichels@rics.bwh.harvard.edu FU NCI NIH HHS [CA50385] NR 37 TC 25 Z9 27 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2006 VL 118 IS 8 BP 2031 EP 2034 DI 10.1002/ijc.21588 PG 4 WC Oncology SC Oncology GA 027ES UT WOS:000236397200026 PM 16284954 ER PT J AU Mulligan, K Parker, RA Komarow, L Grinspoon, SK Tebas, P Robbins, GK Roubenoff, R Dube, MP AF Mulligan, K Parker, RA Komarow, L Grinspoon, SK Tebas, P Robbins, GK Roubenoff, R Dube, MP CA ACT 384 Study Team A5005s Study Team TI Mixed patterns of changes in central and peripheral fat following initiation of antiretroviral therapy in a randomized trial SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE fat distribution; lipodystrophy; DEXA; anthropometry; antiretroviral therapy; HIV ID SEQUENTIAL 3-DRUG REGIMENS; BODY-MASS INDEX; WAIST CIRCUMFERENCE; INFECTED PATIENTS; HIV-1 INFECTION; NAIVE PATIENTS; RISK; MEN; LIPODYSTROPHY; ACCUMULATION AB Introduction: Although peripheral fat loss is a consistent feature Of HIV-associated lipodystrophy, less is known about whether changes in central and peripheral Fat Occur in tandem or independently over time. We examined intraindividual changes in dual-energy x-ray absorptiometry (DEXA) and anthropometry data over 64 weeks after initiation of antiretroviral therapy (ART). Methods: In ACTG 384, ART-naive Subjects were randomized to receive didanosine and stavudine or zidovudine and lamivudine plus efavirenz, nelfinavir, or both. In the metabolic substudy A5005S (N = 329), waist, hip, thigh, and ann circumferences were measured in triplicate. DEXA scanning was performed in 157 Subjects. Results: Individual chanues in limb and trunk Eat at week 64 correlated positively (R.72, P <.001). MOSt Subjects had directionally concordant changes in limb and trunk fat (36% gained and 32% lost in both regions). In 26%, trunk fat increased while limb fat decreased, whereas the reverse occurred in only 6% (P <.001). Changes in waist and hip circumferences also correlated positively (R =.62, P <.001). The proportion of subjects with waist/hip ratio more than.95 (men) or.90 (women) was 34% at baseline and 47% at week 64 (P =.003). fit those who developed increased waist/hip ratio, 76% had increased waist circumference. Conclusions: Individual results obtained by both anthroponletry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation ofART, but changes tended to occur in the same direction. Increased waist/hip ratio was predominantly associated with increased waist circumference. There was no evidence that central fat accumulation and peripheral fat loss are linked in most subjects.001). Changes in waist and hip circumferences also correlated positively (R =.62, P <.001). The proportion of subjects with waist/hip ratio more than .95 (men) or .90 (women) was 34% at baseline and 47% at week 64 (P =.003). fit those who developed increased waist/hip ratio, 76% had increased waist circumference. Conclusions: Individual results obtained by both anthropometry and DEXA show diverse patterns of fat gain and loss over 64 weeks after initiation of ART, but changes tended to occur in the same direction. Increased waist/hip ratio was predominantly associated with increased waist circumference. There was no evidence that central fat accumulation and peripheral fat loss are linked in most subjects. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Div Endocrinol, Dept Med, San Francisco, CA USA. Harvard Univ, Stat & Data Anal Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. Univ Penn, Philadelphia, PA USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA USA. Indiana Univ, Indianapolis, IN USA. RP Dube, MP (reprint author), Wishard Mem Hosp, 1001 W 10th St,Suite OPW-430, Indianapolis, IN 46202 USA. EM mpdube@iupui.edu RI Tebas, Pablo/A-7061-2008; Robbins, Gregory/F-7988-2011 FU NCRR NIH HHS [M01 RR 05096, RR 00750, RR 00036, RR 00052]; NIAID NIH HHS [AI 27668, AI 25897, AI 25903, AI 27664, AI 27675, AI 38855, U01 AI 25859, U01 AI 27673, 1U01 AI 3844, AI 27670, AI 34832-12, AI 38858, U01 AI 025915, U01 AI 025924] NR 25 TC 45 Z9 46 U1 0 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 APR 15 PY 2006 VL 41 IS 5 BP 590 EP 597 DI 10.1097/01.qai.0000214811.72916.67 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 032AZ UT WOS:000236747600007 PM 16652032 ER PT J AU Honeyborne, I Rathod, A Buchli, R Ramduth, D Moodley, E Rathnavalu, P Chetty, S Day, C Brander, C Hildebrand, W Walker, BD Kiepiela, P Goulder, PJR AF Honeyborne, I Rathod, A Buchli, R Ramduth, D Moodley, E Rathnavalu, P Chetty, S Day, C Brander, C Hildebrand, W Walker, BD Kiepiela, P Goulder, PJR TI Motif inference reveals optimal CTL epitopes presented by HLA class I alleles highly prevalent in Southern Africa SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; PEPTIDE BINDING; C MOLECULES; VIRUS; DEFINITION; MHC; INFECTION; POLYMORPHISM; REPERTOIRES; SUPERTYPES AB HIV-specific CTL play a central role in immune control of HIV. The basis for understanding the success or failure of this immune response requires identification of the specific epitopes targeted by CTL. However, in populations most severely affected by the global epidemic, this fundamental knowledge is hindered by the lack of characterization of many of the HLA class I alleles highly prevalent in such populations. Overall, the peptide-binding motif has been determined for a small minority (9%) of HLA class I alleles, with a strong bias toward those alleles prevalent in Caucasoid populations. These studies therefore set out to define; in a South African Zulu/Xhosa population at the epicenter of the epidemic, the epitopes presented by alleles highly prevalent, but for which the peptide-binding motif had not been characterized. Using a method of motif inference, epitopes presented by four such alleles prevalent in the Zulu/Xhosa population of Durban, South Africa, namely, B*3916, B*4201, B*8101, and Cw*1801, are described. Importantly, this approach may additionally facilitate optimization of epitopes in certain instances where conflicting reports in the literature exist regarding the peptide-binding motif, such as for HLA-A*2902, also highly prevalent in southern African populations. These data indicate that the previously anomalous position of HLA-A*2902 among HLA-A alleles, outside any recognized HLA-A supertype, is artifactual, and the true position of the A*2902 motif overlaps those of the A1 and A24 supertypes. C1 Peter Medawar Bldg Pathogen Res, Nuffield Dept Med, Dept Paediat, Oxford, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Pure Prot LLC, Oklahoma City, OK 73104 USA. Univ KwaZuluNatal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. Univ Oklahoma, Hlth Sci Ctr, Dept Immunol & Microbiol, Oklahoma City, OK 73104 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02129 USA. RP Goulder, PJR (reprint author), Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford, England. EM philip.goulder@ndm.ox.ac.uk RI Day, Cheryl/J-9844-2012 FU NIAID NIH HHS [AI46995-01A1, N01-AI-15422]; Wellcome Trust NR 29 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2006 VL 176 IS 8 BP 4699 EP 4705 PG 7 WC Immunology SC Immunology GA 059YV UT WOS:000238769000029 PM 16585563 ER PT J AU Mikhak, Z Fleming, CM Medoff, BD Thomas, SY Tager, AM Campanella, GS Luster, AD AF Mikhak, Z Fleming, CM Medoff, BD Thomas, SY Tager, AM Campanella, GS Luster, AD TI STAT1 in peripheral tissue differentially regulates homing of antigen-specific Th1 and Th2 cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR EXPRESSION; IFN-GAMMA; T-BET; CUTTING EDGE; IN-VIVO; TRANSCRIPTION FACTOR; LINEAGE COMMITMENT; TNF-ALPHA; RESPONSES; ACTIVATION AB Th1 and Th2 effector CD4(+) T cells orchestrate distinct counterregulatory biological responses. To deliver effective tissue Th1- and Th2-type responses, Th1 and Th2 cell recruitment into tissue must be differentially regulated. We show that tissue-derived STAT1 controls the trafficking of adoptively transferred, Ag-specific, wild-type Th1 cells into the lung. Trafficking of Th1 and Th2 cells is differentially regulated as STAT6, which regulates Th2 cell trafficking, had no effect on the trafficking of Th1 cells and STAT1 deficiency did not alter Th2 cell trafficking. We demonstrate that STAT1 control of Thl cell trafficking is not mediated through T-bet. STAT1 controls the recruitment of Th1cells through the induction of CXCL9, CXCL10, CXCL11, and CXCL16, whose expression levels in the lung were markedly decreased in STAT1(-/-) mice. CXCL10 replacement partially restored Th1 cell trafficking in STAT1-deficient mice in vivo, and deficiency in CXCR3, the receptor for CXCL9, CXCL10, and CXCL11, impaired the trafficking of adoptively transferred Thl cells in wild-type mice. Our work identifies that STAT1 in peripheral tissue regulates the homing of Ag-specific Thl cells through the induction of a distinct subset of chemokines and establishes that Th1 and Th2 cell trafficking is differentially controlled in vivo by STAT1 and STAT6, respectively. C1 Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Harvard Univ, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp,Sch Med, Bldg 149-8301,13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu OI Thomas, Seddon/0000-0003-0075-0744 FU NIAID NIH HHS [K08 AI049957, R01 AI40618-08, R01 AI40618-08S1] NR 47 TC 41 Z9 42 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2006 VL 176 IS 8 BP 4959 EP 4967 PG 9 WC Immunology SC Immunology GA 059YV UT WOS:000238769000058 PM 16585592 ER PT J AU Garcia, A Bosques, CJ Wishnok, JS Feng, Y Karalius, BJ Butterton, JR Schauer, DB Rogers, AB Fox, JG AF Garcia, A Bosques, CJ Wishnok, JS Feng, Y Karalius, BJ Butterton, JR Schauer, DB Rogers, AB Fox, JG TI Renal injury is a consistent finding in Dutch belted rabbits experimentally infected with enterohemorrhagic Escherichia coli SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/105th Annual Meeting of the American-Gastroenterological-Association CY MAY 16-20, 2004 CL New Orleans, LA SP Amer Gastroenterol Assoc ID HEMOLYTIC-UREMIC SYNDROME; SHIGA-TOXIN; EPITHELIAL-CELLS; HUMAN PLASMA; IN-VIVO; GLOBOTRIAOSYLCERAMIDE; DIARRHEA; RECEPTOR; THERAPY; DISEASE AB Enterohemorrhagic Escherichia coli ( EHEC) produces Shiga toxin (Stx) and causes renal disease in humans. Dutch Belted (DB) rabbits naturally infected with EHEC O153 develop hemolytic-uremic syndrome-like disease. The aims of this study were to experimentally reproduce O153-induced renal disease in DB rabbits and investigate bacterial and host factors involved in pathogenesis. The pathogenicity of E. coli O157:H7 was also investigated in rabbits. The stx1AB region of O153 was sequenced. By use of liquid chromatography-tandem mass spectrometry, we identified homologs of the Stx receptor, globotriaosylceramide (Gb3), in rabbit kidney extracts. Infected rabbits developed clinical signs and intestinal and kidney lesions. Renal pathological changes consisted of intimal swelling, perivascular edema, erythrocyte fragmentation, capillary thickening, luminal constriction, leukocytic infiltration, mesangial deposits, and changes in Bowman's capsule and space. Sequence analysis of a similar to 7-kb region of the O153 chromosome indicated homology to the Stx1-producing bacteriophage H19B. Our findings indicate that DB rabbits are suitable for the study of the renal manifestations of EHEC infection in humans. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Garcia, A (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,16-873, Cambridge, MA 02139 USA. EM agarcia@mit.edu FU NCRR NIH HHS [T32RR007036]; NIDDK NIH HHS [R01DK059010]; NIEHS NIH HHS [P30ES002109] NR 40 TC 25 Z9 25 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2006 VL 193 IS 8 BP 1125 EP 1134 DI 10.1086/501364 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 023CF UT WOS:000236102200010 PM 16544253 ER PT J AU Stone, ME AF Stone, ME TI The soul of a doctor: Harvard medical students face life and death. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 15 PY 2006 VL 131 IS 7 BP 100 EP 100 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 034CP UT WOS:000236902700198 ER PT J AU Sedding, D Vogel, S Konig, H Tillmans, H Sellers, W Braun-Dullaeus, R AF Sedding, D Vogel, S Konig, H Tillmans, H Sellers, W Braun-Dullaeus, R TI The forkhead transcription factor FoxOla regulates apoptosis of smooth muscle cells by controlling caveolin-1 expression SO MEDIZINISCHE KLINIK LA English DT Meeting Abstract C1 Univ Giessen Klinikum, D-6300 Giessen, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Tech Univ Dresden, Herzzentrum, D-8027 Dresden, Germany. RI Braun-Dullaeus, Ruediger/G-1844-2013 OI Braun-Dullaeus, Ruediger/0000-0003-3888-6532 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0723-5003 J9 MED KLIN JI Med. Klin. PD APR 15 PY 2006 VL 101 IS 4 BP A54 EP A54 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 042WT UT WOS:000237562000166 ER PT J AU Choi, JK Chen, YI Hamel, E Jenkins, BG AF Choi, JK Chen, YI Hamel, E Jenkins, BG TI Brain hemodynamic changes mediated by dopamine receptors: Role of the cerebral microvasculature in dopamine-mediated neurovascular coupling SO NEUROIMAGE LA English DT Article DE cerebral blood volume; dopamine; microvasculature; MRI; neurovascular coupling ID PHARMACOLOGICAL MRI; BLOOD-FLOW; GLUCOSE-UTILIZATION; BASAL GANGLIA; NITRIC-OXIDE; RAT-BRAIN; ACTIVATION; EXPRESSION; VESSELS; COCAINE AB The coupling between neurotransmitter-induced changes in neuronal activity and the resultant hemodynamic response is central to the interpretation of neuroimaging techniques. In the present study, MRI experiments showed that dopamine transporter blockers such as cocaine and dopamine releasers such as amphetamine and D1 receptor agonists induced large positive increases in relative cerebral blood volume (rCBV) that were not sensitive to nitric oxide synthase inhibition. However, D1/D5 receptor antagonism with SCH-23390 prevented or blocked the hemodynamic response without any concomitant effect on dopamine release. Dopamine D2/D3 receptor agonists, in contrast, induced negative changes in rCBV in brain regions corresponding largely to those endowed with these receptors. D1 and D5 receptor mRNAs were expressed in microvessels of responsive brain areas, while D2 and D3 receptors were not consistently associated with the microvascular bed. D3 receptors had an astroglial localization. Together, these experiments show that direct effects of dopamine upon the vasculature cannot be ignored in measuring the hemodynamic coupling associated with dopaminergic drugs. These results further suggest that this coupling is partially mediated through D1/D5 receptors on the microvasculature leading to increased rCBV and through astroglial D3 receptors leading to decreased rCBV These data provide additional support for the role of local post-synaptic events in neurovascular coupling and emphasize that the interpretation of fMRI signals exclusively in terms of neuronal activity may be incomplete. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. McGill Univ, Montreal, PQ H3A 2B4, Canada. Montreal Neurol Inst, Lab Cerebrovasc Res, Montreal, PQ H3A 2B4, Canada. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bgj@nmr.mgh.harvard.edu FU NIDA NIH HHS [5P01 DA09467, R01 DA016187]; Wellcome Trust [R01 DA16187] NR 69 TC 108 Z9 110 U1 0 U2 10 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 APR 15 PY 2006 VL 30 IS 3 BP 700 EP 712 DI 10.1016/j.neuroimage.2005.10.029 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800003 PM 16459104 ER PT J AU Wright, CI Keuthen, NJ Savage, CR Martis, B Williams, D Wedig, M McMullin, K Rauch, SL AF Wright, CI Keuthen, NJ Savage, CR Martis, B Williams, D Wedig, M McMullin, K Rauch, SL TI Brain correlates of negative and positive visuospatial priming in adults SO NEUROIMAGE LA English DT Article DE trichotillomania; obsessive compulsive disorder; inhibition; visuospatial priming; female ID OBSESSIVE-COMPULSIVE-DISORDER; EVENT-RELATED FMRI; FUNCTIONAL MRI; RESPONSE-INHIBITION; PREFRONTAL CORTEX; TOURETTE-SYNDROME; COGNITIVE INHIBITION; COORDINATE SYSTEM; MOTOR INHIBITION; CORTICAL SURFACE AB A balance of inhibitory and facilitatory mechanisms is essential for efficient and goal-directed behaviors. These mechanisms may go awry in several neuropsychiatric disorders characterized by uncontrolled, repetitive behaviors. The visuospatial printing paradigm is a well-established probe of inhibition and facilitation that has been used to demonstrate behavioral deficits in patients with Tourette syndrome and obsessive-compulsive disorder. However, the brain correlates of this visuospatial priming paradigm are not yet well established. In the present study, we used a visuospatial printing paradigm and event-related functional MRI, to probe inhibitory, and facilitatory brain mechanisms in healthy adult women. When subjects performed the negative priming (i.e., inhibitory) task, several regions of the prefrontal cortex were selectively activated relative to the neutral condition. Non-overlapping regions of the prefrontal cortex were deactivated in the positive priming condition. These results support the notion that the prefrontal cortex is involved in both inhibitory and facilitatory processing and demonstrate that this visuospatial priming task shares brain correlates with other positive and negative priming tasks. In conjunction with functional MRI, this visuospatial priming task may be useful for studying the pathophysiology of neuropsychiatric disorders in which deficient inhibitory processing or excessive facilitation is a feature. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Psychiat Neuroimaging Res Program, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Martinos Imaging Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, MO USA. Univ Kansas, Med Ctr, Dept Psychiat, Kansas City, MO USA. Univ Michigan, Ann Arbor, MI 48109 USA. VA Healthcare Syst, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Wright, CI (reprint author), Harvard Univ, Psychiat Neuroimaging Res Program, Sch Med, Massachusetts Gen Hosp, 13th St,Bldg 149,CNY 2613, Charlestown, MA 02129 USA. EM ciwright@partners.org RI Citations, TLC SAB/C-4006-2011 FU NIMH NIH HHS [MH60219, MH64806] NR 75 TC 24 Z9 24 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 APR 15 PY 2006 VL 30 IS 3 BP 983 EP 991 DI 10.1016/j.neuroimage.2005.10.015 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033ZY UT WOS:000236894800031 PM 16300966 ER PT J AU Sanders, NM Figlewicz, DP Taborsky, GJ Wilkinson, CW Daumen, W Levin, BE AF Sanders, NM Figlewicz, DP Taborsky, GJ Wilkinson, CW Daumen, W Levin, BE TI Feeding and neuroendocrine responses after recurrent insulin-induced hypoglycemia SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE hypoglycemia; hypoglycemia counterregulation; hypoglycemia-associated autonomic failure; glucoprivation; food intake ID DEPENDENT DIABETES-MELLITUS; NEUROPEPTIDE-Y; COUNTERREGULATORY RESPONSES; ANTECEDENT HYPOGLYCEMIA; GLUCOSE-UTILIZATION; PERIPHERAL FACTORS; ARCUATE NUCLEUS; WEIGHT-GAIN; FOOD-INTAKE; SUBSEQUENT HYPOGLYCEMIA AB Prior exposure to hypoglycemia impairs neuroendocrine counterregulatory responses (CRR) during subsequent hypoglycemia. Defective CRR to hypoglycemia is a component of the clinical syndrome hypoglycemia-associated autonomic failure (HAAF). Hypoglycemia also potently stimulates food intake, an important behavioral CRR. Because the increased feeding response to hypoglycemia is behavioral and not hormonal, we hypothesized that it may be regulated differently with recurrent bouts of hypoglycemia. To test this hypothesis, we simultaneously evaluated neuroendocrine CRR and food intake in rats experiencing one or three episodes of insulin-induced hypoglycemia. As expected, recurrent hypoglycemia significantly reduced neuroendocrine hypoglycemic CRR. Epinephrine (E), norepinephrine (NE) and glucagon responses 120 min after insulin injection were significantly reduced in recurrent hypoglycemic rats, relative to rats experiencing hypoglycemia for the first time. Despite these neuroendocrine impairments, food intake was significantly elevated above baseline saline intake whether rats were experiencing a first (hypoglycemia: 3.4 +/- 0.4 g vs. saline: 0.94 +/- 0.3 g, P < 0.05) or third hypoglycemic episode (hypoglycerma: 3.8 +/- 0.3 g vs. saline: 1.2 +/- 0.3 g, P < 0.05). These findings demonstrate that food intake elicited in response to hypoglycemia is not impaired as a result of recurrent hypoglycemia. Thus, neuroendocrine and behavioral (stimulation of food intake) CRR are differentially regulated by recurrent hypoglycemia experience. (c) 2006 Elsevier Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Div Geriatr Res, Educ & Clin Ctr, Seattle, WA USA. Seattle Inst Biomed & Clin Res & Neurol Serv, Dept Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA. RP Sanders, NM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Educ & Clin Ctr, S-151,1660 So Columbian Way, Seattle, WA 98108 USA. EM sandersn@u.washington.edu FU NIDDK NIH HHS [DK 40963, DK 50154, DK 53181] NR 53 TC 20 Z9 21 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR 15 PY 2006 VL 87 IS 4 BP 700 EP 706 DI 10.1016/j.physbeh.2006.01.007 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 035HN UT WOS:000236991600008 PM 16492385 ER PT J AU Crall, TS Gilula, LA Kim, YJJ Cho, YS Pilgram, T Riew, KD AF Crall, TS Gilula, LA Kim, YJJ Cho, YS Pilgram, T Riew, KD TI The diagnostic effect of various needle tip positions in selective lumbar nerve blocks: An analysis of 1202 injections SO SPINE LA English DT Article DE nerve blocks; nerve root injection; radicular pain; herniated disc; stenosis AB Study Design. Retrospective chart review. Objective. To determine the effect of various needle tip positions on immediate postinjection pain in selective lumbar nerve blocks. Summary of Background Data. To our knowledge, no large study has examined the effect of various needle tip positions within or adjacent to the intervertebral foramen on immediate pain outcome. Methods. A total of 1774 cases of intervertebral lumbar nerve blocks performed by our radiology staff between April 7, 1997 and May 31, 2002, were reviewed. Of the 1774 cases, 1202 met the study criteria (i.e., a singlelevel injection in an adult). The position of the needle tip and degree of immediate postinjection pain relief were examined. Results. The blocks resulted in an average pain reduction of 4.14 U, as graded on a 0-10 ordinate scale (95% confidence interval 3.98-4.30). The degree of pain reduction was not associated with the needle tip position. Conclusions. Our results suggest that precise needle tip position within or adjacent to the intervertebral foramen made no difference on immediate pain reduction. These findings allow the practitioner more freedom in performing an injection. This study does not evaluate the long-term effects of various needle tip positions in selective lumbar nerve blocks. C1 Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Dept Orthopaed Surg, St Louis, MO USA. RP Gilula, LA (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, 510 S Kingshighway, St Louis, MO 63110 USA. EM gilulal@mir.wustl.edu NR 8 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 15 PY 2006 VL 31 IS 8 BP 920 EP 922 DI 10.1097/01.brs.0000209325.52986.da PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 034IO UT WOS:000236922700013 PM 16622382 ER PT J AU Meier, M Nitschke, M Weidtmann, B Jabs, WJ Wong, WC Suefke, S Steinhoff, J Fricke, L AF Meier, M Nitschke, M Weidtmann, B Jabs, WJ Wong, WC Suefke, S Steinhoff, J Fricke, L TI Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: A Randomized controlled trial SO TRANSPLANTATION LA English DT Article DE cyclosporine; tacrolimus; chronic allograft nephropathy; transplantation ID CARDIOVASCULAR RISK PROFILE; RENAL-TRANSPLANT RECIPIENTS; CHRONIC REJECTION; IMMUNOSUPPRESSION; SURVIVAL; MICROEMULSION; HYPERTENSION; MULTICENTER; LIFE AB Background. Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN. Methods. Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months. Results. SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 mu mol/L; TaC6: 261 +/- 70 mu mol/L, P < 0.001; Tac(12): 254 +/- 55 mu mol/L, P < 0.001; TaC36: 255 +/- 78 mu mol/L, P=0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 mu mol/L, CyA,2: 333 98 mu mol/L, P < 0.001; CyA36: 317 +/- 89 mu mol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P=0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12):83 +/- 14, P < 0.001; TaC16:60 +/- 12, CyA(36):84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12):2.5 +/- 0.5mmol/L, CyA(12): 3.5 +/- 0.6mmol/L, P < 0.001). Conclusion. Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival. C1 Med Univ Lubeck, Sch Med, Dept Internal Med 1, Transplantat Ctr, D-23538 Lubeck, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Meier, M (reprint author), Med Univ Lubeck, Sch Med, Dept Internal Med 1, Transplantat Ctr, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM markus.meier@innere1.uni-luebeck.de NR 25 TC 23 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2006 VL 81 IS 7 BP 1035 EP 1040 DI 10.1097/01.tp.0000220480.84449.71 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 034VL UT WOS:000236958600018 PM 16612281 ER PT J AU Tseng, YL Moran, K Dor, FJMF Sanderson, TM Li, W Lancos, CJ Schuurman, HJ Sachs, DH Cooper, DKC AF Tseng, YL Moran, K Dor, FJMF Sanderson, TM Li, W Lancos, CJ Schuurman, HJ Sachs, DH Cooper, DKC TI Elicited antibodies in baboons exposed to tissues from alpha 1,3-galactosyltransferase gene-knockout pigs SO TRANSPLANTATION LA English DT Article DE antibody; elicited; nonGal; baboon; pig; alpha 1,3-galactosyltransferase gene-knockout; xenotransplantation ID HEART-TRANSPLANTATION; CELL TRANSPLANTATION; INITIAL-EXPERIENCE; NATURAL ANTIBODIES; XENOANTIGENS; SPECIFICITY; PRIMATES AB Background. This study investigates anti-nonGal antibodies (Abs) in baboons after alpha 1,3-galactosyltransferase gene-knockout (GaIT-KO) pig heart transplantation (Tx). Methods. Four baboons underwent pig heart Tx under chronic immunosuppression, which was discontinued after graftectomy. During follow-up, one baboon also received a pig splenocyte infusion. Hearts and splenocytes were from GaIT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy, sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using PBMC from SLA aa, cc, and dd haplotypes. Results. Before heart Tx, no baboon had anti-nonGal Abs demonstrable by binding or cytotoxicity to GaIT-KO PBMC. All four baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and three sera from baboons showed cytotoxicity to GaIT-KO PBMC of SLA dd haplotype. After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)). Conclusions. Anti-nonGal Abs developed after GaIT-KO pig heart Tx into baboons. The most potent of these antibodies appeared to detect antigens shared by the three pig haplotypes tested. It remains unclear whether these antibodies are directed towards shared SLA determinants or other pig antigens, and whether antibodies with specificity for allelic SLA determinants are also present, but at lower titer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Immerge BioTherapeut, Cambridge, MA USA. RP Cooper, DKC (reprint author), Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Biomed Sci Tower E,Room E1550A,200 Lothrop St, Pittsburgh, PA 15261 USA. EM cooperdk@upmc.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1P01 AI45897] NR 24 TC 28 Z9 30 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 APR 15 PY 2006 VL 81 IS 7 BP 1058 EP 1062 DI 10.1097/01.tp.0000197555.16093.98 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 034VL UT WOS:000236958600021 PM 16612284 ER PT J AU Saidarriaga, OA Perez, LE Travi, BL Melby, PC AF Saidarriaga, OA Perez, LE Travi, BL Melby, PC TI Selective enhancement of the type 1 cytokine response by expression of a canine interleukin (IL)-12 fused heterodimeric DNA SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE canine; interleukin-12; vaccine adjuvant; IFN-gamma ID BLOOD MONONUCLEAR-CELLS; STIMULATORY FACTOR INTERLEUKIN-12; CELLULAR IMMUNE-RESPONSE; IN-VIVO; LEISHMANIA-MAJOR; PROTECTIVE IMMUNITY; VISCERAL LEISHMANIASIS; INTERFERON-GAMMA; MESSENGER-RNA; TH1 RESPONSE AB Interleukin-12 (IL-12) is a heterodimeric cytokine that is a principal mediator of the innate immune response and modulator of acquired cell-mediated immunity. Administration of exogenous IL-12 can direct the host adaptive T cell response toward a type I phenotype. The co-administration of IL-12 with vaccine antigen, has been shown to augment the vaccine-induced T(H)1 response and protection against intracellular pathogens. We show here that a canine IL-12 DNA, constructed by fusing the p35 and p40 Subunit cDNAs with an interspacing linker, generated stable IL-12 transcripts when placed under control of a strong constitutive promoter. The protein expressed from this fused cDNA wag fully functional in promoting a type 1 (IFN-gamma) and Suppressing a type 2 (IL-4) cytokine response following both in vitro transfection of a canine cell line and in vivo delivery to dogs. This DNA construct may be useful as an adjuvant for vaccines that target tumors or intracellular pathogens of the dog. (c) 2005 Elsevier B.V. All rights reserved. C1 S Texas Vet Hlth Care Syst, Res Serv, Dept Vet Affairs, Med Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol & Immunol, San Antonio, TX 78284 USA. Ctr Int Entrenamiento & Invest Med, Cali AA53909, Colombia. RP Melby, PC (reprint author), S Texas Vet Hlth Care Syst, Res Serv, Dept Vet Affairs, Med Ctr, 7400 Merton Minter Dr,Mailstop 151, San Antonio, TX 78229 USA. EM melby@uthscsa.edu NR 40 TC 0 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD APR 15 PY 2006 VL 110 IS 3-4 BP 377 EP 388 DI 10.1016/j.vetimm.2005.11.003 PG 12 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 023VQ UT WOS:000236154700019 ER PT J AU Leech, C Lohse, P Stanojevic, V Lechner, A Goke, B Spitzweg, C AF Leech, C Lohse, P Stanojevic, V Lechner, A Goke, B Spitzweg, C TI Identification of a novel inactivating R465Q mutation of the calcium-sensing receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE calcium-sensing receptor; inactivating mutation; familial hypocalciuric hypercalcemia ID FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; AUTOSOMAL-DOMINANT HYPOCALCEMIA; EXTRACELLULAR CALCIUM; FUNCTIONAL-CHARACTERIZATION; CA2+-SENSING RECEPTOR; BENIGN HYPERCALCEMIA; A986S POLYMORPHISM; SERUM-CALCIUM; CELL-SURFACE AB In this study, we describe a 52-year-old woman, who was diagnosed with familial benign hypocalciuric hypercalcemia (FBHH), a condition characterized by hypercalcemia, low urinary calcium excretion, and normal parathyroid hormone PTH levels, resulting from inactivating mutations of the calcium-sensing receptor (CaSR). In order to identify and characterize the underlying mutation in the CASR gene, direct sequence analysis of CASR exons 2-7 was performed, and functional activity was examined by transient transfection of human embryonic kidney (HEK-293) cells with wild-type and mutant CaSRs, followed by intracellular calcium measurement using fluorometry, and Western blot analysis. Sequence analysis demonstrated, in addition to the already described A986S polymorphism, a novel heterozygous G -> A Substitution in CASR exon 5 that causes an arginine to glutamine substitution at codon 465 (R465Q). Functional analysis showed a rightward shift of the dose-response curve with a significant increase of the EC50 from 5.4 mM of the CaSR carrying the A986S polymorphism alone to 11.3 mM of the CaSR carrying the R465Q mutation in the presence of the A986S polymorphism. Western blot analysis of membrane protein revealed an even higher expression level of the R465Q mutant protein compared to wild-type CaSR. In conclusion, we identified a novel heterozygous loss-of-function R465Q mutation of the CASR gene, which is characterized by a blunted response to calcium Stimulation, thereby causing FBHH. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Munich, Dept Internal Med 2, Munich, Germany. Univ Munich, Inst Clin Chem, Munich, Germany. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02115 USA. RP Spitzweg, C (reprint author), Univ Munich, Dept Internal Med 2, Marchioninistr 15, Munich, Germany. EM Christine.Spitzweg@med.uni-muenchen.de NR 23 TC 8 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 14 PY 2006 VL 342 IS 3 BP 996 EP 1002 DI 10.1016/j.bbrc.2006.02.018 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 024AZ UT WOS:000236168600044 PM 16598859 ER PT J AU McGill, GG Haq, R Nishimura, EK Fisher, DE AF McGill, GG Haq, R Nishimura, EK Fisher, DE TI c-Met expression is regulated by Mitf in the melanocyte lineage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; MICROPHTHALMIA TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; NEURAL CREST; STIMULATING HORMONE; SIGNAL-TRANSDUCTION; MUSCLE DEVELOPMENT; HGF RECEPTOR; CELLS AB Hepatocyte growth factor (HGF)/c-Met signaling is thought to be a key pathway in both melanocyte development and melanoma metastasis. Here, HGF stimulation of melanocytes was seen to upregulate c-Met expression. In an effort to decipher the mechanism by which HGF up-regulates its receptor, we found that c-Met is a direct transcriptional target of Mitf. This was confirmed with chromatin immunoprecipitation experiments of the human c-Met promoter, as well as by the ability of adenovirally expressed Mitf to modulate endogenous c-Met protein levels in melanocytes. Disruption of Mitf blocked HGF-dependent increases in endogenous c-Met message and protein levels, indicating that HGF regulates its own receptor levels via Mitf. Finally, dominant-negative inhibition of Mitf resulted in profound resistance of melanocytes and melanoma cells to HGF-dependent matrix invasion, suggesting a physiologic role for this pathway in melanocytic development and melanoma. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Johns Hopkins Univ Hosp, Dept Internal Med, Baltimore, MD 21205 USA. Hokkaido Univ, Grad Sch Med, Dept Dermatol, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Grad Sch Med, Creat Res Inst Sousei, Kita Ku, Sapporo, Hokkaido 0608638, Japan. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu NR 55 TC 97 Z9 100 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 14 PY 2006 VL 281 IS 15 BP 10365 EP 10373 DI 10.1074/jbc.M513094200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029WE UT WOS:000236594300065 PM 16455654 ER PT J AU von Boehmer, H AF von Boehmer, H TI Immunology - Thoracic thymus, exclusive no longer SO SCIENCE LA English DT Editorial Material 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, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 9 TC 4 Z9 5 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 14 PY 2006 VL 312 IS 5771 BP 206 EP 207 DI 10.1126/science.1126403 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 032HK UT WOS:000236765300030 PM 16614204 ER PT J AU Krasner, CN Roche, M Horowitz, NS Supko, JG Lee, SI Oliva, E Harris, NL Fuller, AF AF Krasner, CN Roche, M Horowitz, NS Supko, JG Lee, SI Oliva, E Harris, NL Fuller, AF TI Case 11-2006: A 54-year-old woman with a mass in the pelvis - Mixed high-grade serous papillary and transitional-cell carcinoma of the fallopian tube, FIGO stage IIIC. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GYNECOLOGIC-ONCOLOGY-GROUP; EPITHELIAL OVARIAN-CANCER; PRIMARY CYTOREDUCTIVE SURGERY; INTRAPERITONEAL CISPLATIN; INTRAVENOUS CISPLATIN; CLINICOPATHOLOGICAL ANALYSIS; RANDOMIZED-TRIAL; PACLITAXEL; CARBOPLATIN; SURVIVAL C1 Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Clin Pharmacol Lab, 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 Obstet Gynecol & Reprod Biol, 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 Krasner, CN (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Womens Canc, Boston, MA 02114 USA. NR 57 TC 6 Z9 6 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 13 PY 2006 VL 354 IS 15 BP 1615 EP 1625 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 031WW UT WOS:000236736900012 PM 16611953 ER PT J AU Berry, DA Cirrincione, C Henderson, IC Citron, ML Budman, DR Goldstein, LJ Martino, S Perez, EA Muss, HB Norton, L Hudis, C Winer, EP AF Berry, DA Cirrincione, C Henderson, IC Citron, ML Budman, DR Goldstein, LJ Martino, S Perez, EA Muss, HB Norton, L Hudis, C Winer, EP TI Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED-TRIAL; ADJUVANT THERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN THERAPY; TRASTUZUMAB; RECURRENCE; METAANALYSIS; COMBINATION; EXPRESSION; SURVIVAL AB Context Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. Objective To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. Design, Setting, and Patients Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. Main Outcome Measures Disease-free and overall survival. Results For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. Conclusion Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Albert Einstein Coll Med, Lake Success, NY USA. N Shore Univ Hosp, Manhasset, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Mayo Clin & Mayo Fdn, Jacksonville, FL USA. Univ Vermont, Vermont Reg Canc Ctr, Burlington, VT USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berry, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, 1515 Holcombe Blvd,Unit 447, Houston, TX 77030 USA. EM dberry@mdanderson.org FU NCI NIH HHS [CA31946, U01 CA088278, U10 CA031946, U10 CA033601] NR 34 TC 404 Z9 433 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 12 PY 2006 VL 295 IS 14 BP 1658 EP 1667 DI 10.1001/jama.295.14.1658 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 031LY UT WOS:000236707300021 PM 16609087 ER PT J AU O'Donoghue, M Morrow, DA Sabatine, MS Murphy, SA McCabe, CH Cannon, CP Braunwald, E AF O'Donoghue, M Morrow, DA Sabatine, MS Murphy, SA McCabe, CH Cannon, CP Braunwald, E TI Lipoprotein-associated phospholipase A(2) and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin or atorVastatin evaluation and infection therapy-thrombolysis in myocardial infarction) trial SO CIRCULATION LA English DT Article DE prognosis; inflammation; myocardial infarction; lipoproteins ID ACTIVATING-FACTOR-ACETYLHYDROLASE; C-REACTIVE PROTEIN; LOW-DENSITY-LIPOPROTEIN; MIDDLE-AGED MEN; HEART-DISEASE; ARTERY-DISEASE; STATIN THERAPY; OXIDIZED PHOSPHOLIPIDS; HUMAN-PLASMA; RISK-FACTORS AB Background-Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is associated with the risk of cardiovascular (CV) events in population-based studies. The prognostic value of Lp-PLA(2) in patients with acute coronary syndromes (ACS) has not been established. Methods and Results-Plasma levels of Lp-PLA(2) activity were measured at baseline (n=3648) and 30 days (n=3265) in patients randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial. The primary end point was death, myocardial infarction, unstable angina, revascularization, or stroke (mean follow-up 24 months). At baseline after ACS, the risk of recurrent CV events was similar across all quintiles of Lp-PLA(2) activity (P-trend=0.88). Overall, mean levels of Lp-PLA(2) were lower at 30 days of follow-up than at baseline (35.7 versus 40.9 nmol.min(-1).mL(-1), P<0.001). In particular, treatment with atorvastatin 80 mg/d was associated with a 20% reduction in Lp-PLA(2) activity (P<0.001), whereas Lp-PLA(2) rose 3.6% with pravastatin 40 mg/d (P<0.001). Patients with 30-day Lp-PLA(2) activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile (26.4% versus 17.6%, P-trend=0.002). After adjustment for cardiac risk factors, treatments, achieved low-density lipoprotein (LDL), and C-reactive protein, Lp-PLA(2) activity in the highest quintile remained independently associated with a higher risk of recurrent CV events (adjusted hazard ratio 1.33, 95% confidence interval [CI] 1.01 to 1.74). Conclusions-Lp-PLA(2) is not useful for risk stratification when measured early after ACS. At 30 days, Lp-PLA(2) activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM dmorrow@partners.org FU NHLBI NIH HHS [U01 HL083-1341] NR 41 TC 143 Z9 148 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 11 PY 2006 VL 113 IS 14 BP 1745 EP 1752 DI 10.1161/CIRCULATIONAHA.105.612630 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 031JS UT WOS:000236701300009 PM 16537575 ER PT J AU Zhu, CW Scarmeas, N Torgan, R Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, CW Scarmeas, N Torgan, R Albert, M Brandt, J Blacker, D Sano, M Stern, Y TI Clinical features associated with costs in early AD - Baseline data from the Predictors Study SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE CARE; APOE GENOTYPE; ECONOMIC COST; MOTOR SIGNS; DEMENTIA; SEVERITY; IMPACT; SYMPTOMS; MEDICARE; MODELS AB Background: Few studies on cost of caring for patients with Alzheimer disease (AD) have simultaneously considered multiple dimensions of disease costs and detailed clinical characteristics. Objective: To estimate empirically the incremental effects of patients' clinical characteristics on disease costs. Methods: Data are derived from the baseline visit of 180 patients in the Predictors Study, a large, multicenter cohort of patients with probable AD followed from early stages of the disease. All patients initially lived at home, in retirement homes, or in assisted living facilities. Costs of direct medical care included hospitalizations, outpatient treatment and procedures, assistive devices, and medications. Costs of direct nonmedical care included home health aides, respite care, and adult day care. Indirect costs were measured by caregiving time. Patients' clinical characteristics included cognitive status, functional capacity, psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, and duration of illness. Results: A 1-point increase in the Blessed Dementia Rating Scale score was associated with a $1,411 increase in direct medical costs and a $2,718 increase in unpaid caregiving costs. Direct medical costs also were $3,777 higher among subjects with depressive symptoms than among those who were not depressed. Conclusions: Medical care costs and unpaid caregiving costs relate differently to patients' clinical characteristics. Poorer functional status is associated with higher medical care costs and unpaid caregiving costs. Interventions may be particularly useful if targeted in the areas of basic and instrumental activities of daily living. C1 Mt Sinai Sch Med, Ctr Geriatr Res Educ & Clin, New York, NY USA. Mt Sinai Sch Med, Program Res Serious Phys & Mental Illness, New York, NY USA. Mt Sinai Sch Med, Brookdale Dept Geriatr, Bronx VA Med Ctr, Targeted Res Enhancement Program, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Zhu, CW (reprint author), Ctr Geriatr Res Educ & Clin, 130 Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370, U01AG010483] NR 54 TC 47 Z9 48 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 11 PY 2006 VL 66 IS 7 BP 1021 EP 1028 DI 10.1212/01.wnl.0000204189.18698.c7 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 030ZG UT WOS:000236673300012 PM 16606913 ER PT J AU Jin, M Song, G Carman, CV Kim, YS Astrof, NS Shimaoka, M Wittrup, KD Springer, TA AF Jin, M Song, G Carman, CV Kim, YS Astrof, NS Shimaoka, M Wittrup, KD Springer, TA TI Directed evolution to probe protein allostery and integrin I domains of 200,000-fold higher affinity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID YEAST SURFACE DISPLAY; A-DOMAIN; ADHESION; LIGAND; LFA-1; CONFORMATION; PATHWAY; BINDING; STATES AB Understanding allostery may serve to both elucidate mechanisms of protein regulation and provide a basis for engineering active mutants. Herein we describe directed evolution applied to the integrin alpha(L) inserted domain for studying allostery by using a yeast surface display system. Many hot spots for activation are identified, and some single mutants exhibit remarkable increases of 10,000-fold in affinity for a physiological ligand, intercellular adhesion molecule-1. The location of activating mutations traces out an allosteric interface in the interior of the inserted domain that connects the ligand binding site to the alpha 7-helix, which communicates allostery to neighboring domains in intact integrins. The combination of two activating mutations (F265S/F292G) leads to an increase of 200,000-fold in affinity to intercellular adhesion molecule-1. The F265S/F292G mutant is potent in antagonizing lymphocyte function-associated antigen 1-dependent lymphocyte adhesion, aggregation, and transmigration. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res & Dev Pathol, Boston, MA 02115 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res & Dev Pathol, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Jin, Moonsoo/D-6128-2011; Carman, Christopher/L-8108-2016; OI Carman, Christopher/0000-0001-7358-2548; Kim, Yong-Sung/0000-0003-2673-1509 FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798, R37 CA031798-26] NR 21 TC 46 Z9 47 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 APR 11 PY 2006 VL 103 IS 15 BP 5758 EP 5763 DI 10.1073/pnas.0601164103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200024 PM 16595626 ER PT J AU Bardeesy, N Aguirre, AJ Chu, GC Cheng, KH Lopez, LV Hezel, AF Feng, B Brennan, C Weissleder, R Mahmood, U Hanahan, D Redston, MS Chin, L DePinho, RA AF Bardeesy, N Aguirre, AJ Chu, GC Cheng, KH Lopez, LV Hezel, AF Feng, B Brennan, C Weissleder, R Mahmood, U Hanahan, D Redston, MS Chin, L DePinho, RA TI Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE array comparative genomic hybridization; mouse models; pancreatic cancer; KRAS; tumor suppressor ID TUMOR-SUPPRESSOR GENE; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; CELL-PROLIFERATION; CANCER STATISTICS; RAS MUTATIONS; K-RAS; P53; CARCINOMA; EXPRESSION AB Activating KRAS mutations and p16(Ink4a) inactivation are near universal events in human pancreatic ductal adenocarcinoma (PDAC). In mouse models, Kras(G12D) initiates formation of premalignant pancreatic ductal lesions, and loss of either Ink4a/Arf (p16(Ink4a)/p19(Arf)) or p53 enables their malignant progression. As recent mouse modeling studies have suggested a less prominent role for p16(Ink4a) in constraining malignant progression, we sought to assess the pathological and genomic impact of inactivation of P16(Ink4a), p19(Arf), and/or p53 in the Kras(G12D) model. Rapidly progressive PDAC was observed in the setting of homozygous deletion of either p53 or p16(Ink4a), the latter with intact germ-line p53 and p19(Arf) sequences. Additionally, Kras(G12D) in the context of heterozygosity either for p53 plus p16(Ink4a) or for p16(Ink4a)/p19(Arf) produced PDAC with longer latency and greater propensity for distant metastases relative to mice with homozygous deletion of p53 or p16(Ink4a)/p19(Arf). Tumors from the double-heterozygous cohorts showed frequent p16(Ink4a) inactivation and loss of either p53 or p19(Arf). Different genotypes were associated with specific histopathologic characteristics, most notably a trend toward less differentiated features in the homozygous p16(Ink4a)/p19(Arf) mutant model. High-resolution genomic analysis revealed that the tumor suppressor genotype influenced the specific genomic patterns of these tumors and showed overlap in regional chromosomal alterations between murine and human PDAC. Collectively, our results establish that disruptions of p16(Ink4a) and the p19(ARF)-p53 circuit play critical and cooperative roles in PDAC progression, with specific tumor suppressor genotypes provocatively influencing the tumor biological phenotypes and genomic profiles of the resultant tumors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Neurosurg Serv, New York, NY 10021 USA. Univ Calif San Francisco, Dept Biochem, Ctr Diabet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 NR 43 TC 269 Z9 278 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 2006 VL 103 IS 15 BP 5947 EP 5952 DI 10.1073/pnas.0601273103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200056 PM 16585505 ER PT J AU Dykxhoorn, DM Schlehuber, LD London, IM Lieberman, J AF Dykxhoorn, DM Schlehuber, LD London, IM Lieberman, J TI Determinants of specific RNA interference-mediated silencing of human beta-globin alleles differing by a single nucleotide polymorphism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sickle cell anemia; specificity of silencing; hemoglobin E; hemoglobin S ID SICKLE-CELL-DISEASE; SIRNA; RECOGNITION; DELIVERY; ANEMIA; GENE AB A single nucleotide polymorphism (SNP) in the sickle beta-globin gene (ps) leads to sickle cell anemia. Sickling increases sharply with deoxy sickle Hb concentration and decreases with increasing fetal gamma-globin concentration. Measures that decrease sickle Hb concentration should have an antisickling effect. RNA interference (RNAi) uses small interfering (si)RNAs for sequence-specific gene silencing. A beta(s) siRNA with position 10 of the guide strand designed to align with the targeted beta(S) SNP specifically silences beta(S) gene expression without affecting the expression of the gamma-globin or normal beta-globin (beta(A)) genes. Silencing is increased by altering the 5' end of the siRNA antisense (guide) strand to enhance its binding to the RNA-induced silencing complex (RISC). Specific beta(S) silencing was demonstrated by using a luciferase reporter and full-length beta(S) cDNA transfected into HeLa cells and mouse erythroleukemia cells, where it was expressed in the context of the endogenous P-globin gene promoter and the locus control region enhancers. When this strategy was used to target PE, silencing was not limited to the mutant gene but also targeted the normal beta(A) gene. siRNAs, mismatched with their target at position 10, guided mRNA cleavage in all cases except when two bulky purines were aligned. The specific silencing of the beta(S)-globin gene, as compared with beta(E), as well as studies of silencing SNP mutants in other diseases, indicates that siRNAs developed to target a disease-causing SNP will be specific if the mutant residue is a pyrimidine and the normal residue is a purine. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP London, IM (reprint author), Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM imlondon@mit.edu RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NHLBI NIH HHS [5 T32 HL007556-19, P01 HL 055435-11, P01 HL055435, T32 HL007556]; NIAID NIH HHS [AI056900, U19 AI056900] NR 24 TC 36 Z9 37 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 2006 VL 103 IS 15 BP 5953 EP 5958 DI 10.1073/pnas.0601309103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 034AK UT WOS:000236896200057 PM 16585504 ER PT J AU Tricoci, P Roe, MT Mulgund, J Newby, LK Smith, SC Pollack, CV Fintel, DJ Cannon, CP Bhatt, DL Gibler, WB Ohman, EM Peterson, ED Harrington, RA AF Tricoci, P Roe, MT Mulgund, J Newby, LK Smith, SC Pollack, CV Fintel, DJ Cannon, CP Bhatt, DL Gibler, WB Ohman, EM Peterson, ED Harrington, RA TI Clopidogrel to treat patients with non-ST-segment elevation acute coronary syndromes after hospital discharge SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; HEART-FAILURE; LONG-TERM; CARE; GUIDELINES; THERAPY; COMBINATION; MANAGEMENT; SPECIALTY AB Background: Clopidogrel added to aspirin improved out-comes after hospitalization in patients with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial, regardless of in-hospital treatment approach. The American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for treating NSTE ACS thus recommend prescribing clopidogrel plus aspirin at discharge for all patients, not just for those undergoing percutaneous coronary intervention (PCI). Methods: We studied 61052 patients with high-risk NSTE ACS (defined as the presence of positive cardiac markers and/or ischemic ST-segment changes) from January 2002 through December 2003 at 461 US hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative. We evaluated temporal trends of clopidogrel use at discharge since the ACC/AHA 2002 Guidelines update and examined variables associated with clopidogrel use in patients who did not undergo PCI. Results: A total of 34319 patients (56.2%) received clopidogrel when they were discharged from the hospital. Among patients who did not undergo PCI, variables associated with receiving clopidogrel at discharge included prior PCI, coronary artery bypass grafting (CABG), stroke, or myocardial infarction; hypercholesterolemia; elevated cardiac markers; and cardiology inpatient care. By late 2003, 96.3% of patients who underwent PCI received clopidogrel at discharge, compared with 42.8% of patients who did not undergo cardiac catheterization and 23.5% of the patients who underwent CABG, although clopidogrel prescription at discharge increased in each of these treatment groups from 2002 to 2003. Conclusion: Since release of the ACC/AHA Guidelines recommendations for treatment of NSTE ACS, prescription of clopidogrel at hospital discharge in patients with NSTE ACS who are treated with medical therapy alone and in those who undergo CABG has increased, but most of these patients still do not receive clopidogrel at discharge. C1 Duke Univ, Clin Res Inst, Durham, NC 27705 USA. Duke Univ, Sch Med, Div Cardiol, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Penn Hosp, Philadelphia, PA 19107 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Cincinnati, Sch Med, Cincinnati, OH USA. RP Tricoci, P (reprint author), Duke Univ, Clin Res Inst, Desk 7583,2400 Pratt St, Durham, NC 27705 USA. EM trico001@dcri.duke.edu NR 21 TC 40 Z9 41 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 10 PY 2006 VL 166 IS 7 BP 806 EP 811 DI 10.1001/archinte.166.7.806 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 031BT UT WOS:000236679800015 PM 16606819 ER PT J AU Zhang, XG Lu, X Shi, Q Xu, XQ Leung, HCE Harris, LN D Iglehart, J Miron, A Liu, JS Wong, WH AF Zhang, XG Lu, X Shi, Q Xu, XQ Leung, HCE Harris, LN D Iglehart, J Miron, A Liu, JS Wong, WH TI Recursive SVM feature selection and sample classification for mass-spectrometry and microarray data SO BMC BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION PATTERNS; MOLECULAR CLASSIFICATION; PROTEOMIC PATTERNS; BREAST-CANCER; DISCOVERY; SERUM; BIAS AB Background: Like microarray-based investigations, high-throughput proteomics techniques require machine learning algorithms to identify biomarkers that are informative for biological classification problems. Feature selection and classification algorithms need to be robust to noise and outliers in the data. Results: We developed a recursive support vector machine (R-SVM) algorithm to select important genes/biomarkers for the classification of noisy data. We compared its performance to a similar, state-of-the-art method (SVM recursive feature elimination or SVM-RFE), paying special attention to the ability of recovering the true informative genes/biomarkers and the robustness to outliers in the data. Simulation experiments show that a 5%-similar to 20% improvement over SVM-RFE can be achieved regard to these properties. The SVM-based methods are also compared with a conventional univariate method and their respective strengths and weaknesses are discussed. R-SVM was applied to two sets of SELDI-TOF-MS proteomics data, one from a human breast cancer study and the other from a study on rat liver cirrhosis. Important biomarkers found by the algorithm were validated by follow-up biological experiments. Conclusion: The proposed R-SVM method is suitable for analyzing noisy high-throughput proteomics and microarray data and it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features. The multivariate SVM-based method outperforms the univariate method in the classification performance, but univariate methods can reveal more of the differentially expressed features especially when there are correlations between the features. C1 Tsing Hua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China. Tsing Hua Univ, Dept Automat, Beijing 100084, Peoples R China. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Genome Inst Singapore, Med Proteom & Bioanal Sect, Singapore, Singapore. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Zhang, XG (reprint author), Tsing Hua Univ, Bioinformat Div, TNLIST, Beijing 100084, Peoples R China. EM xgzhang@tsinghua.edu.cn; xinlu@hsph.harvard.edu; Qian_Shi@dfci.harvard.edu; jxu@escellinternational.com; leunge@gis.a-star.edu.sg; lyndsay_harris@dfci.harvard.edu; JIGLEHART@PARTNERS.ORG; Alexander_Miron@dfci.harvard.edu; jliu@stat.harvard.edu; whwong@stanford.edu FU NHGRI NIH HHS [1R01HG02341, R01 HG002341, R01 HG002518, R01HG02518] NR 34 TC 130 Z9 141 U1 1 U2 29 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD APR 10 PY 2006 VL 7 AR 197 DI 10.1186/1471-2105-7-1-197 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 038XT UT WOS:000237263600001 PM 16606446 ER PT J AU Christiani, DC AF Christiani, DC TI Genetic susceptibility to lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID POLYMORPHISMS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 10 PY 2006 VL 24 IS 11 BP 1651 EP 1652 DI 10.1200/JCO.2005.05.4114 PG 2 WC Oncology SC Oncology GA 032OL UT WOS:000236783900002 PM 16549817 ER PT J AU Shapiro, GI AF Shapiro, GI TI Cyclin-dependent kinase pathways as targets for cancer treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; FLAVOPIRIDOL INDUCES APOPTOSIS; MANTLE-CELL LYMPHOMA; 72-HOUR CONTINUOUS-INFUSION; CYC202 R-ROSCOVITINE; RETINOBLASTOMA PROTEIN-PHOSPHORYLATION; SPINDLE ASSEMBLY CHECKPOINT; GROWTH-FACTOR EXPRESSION; MULTIPLE-MYELOMA CELLS; BREAST-CARCINOMA CELLS AB Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic events cause universal overactivity of the cell cycle cdks in human cancer, and their inhibition can lead to both cell cycle arrest and apoptosis. However, built-in redundancy may limit the effects of highly selective cdk inhibition. Cdk4/6 inhibition has been shown to induce potent G, arrest in vitro and tumor regression in vivo; cdk2/1 inhibition has the most potent effects during the S and G(2) phases and induces E2F transcription factor-dependent cell death. Modulation of cdk2 and cdk1 activities also affects survival checkpoint responses after exposure to DNA-damaging and microtubule-stabilizing agents. The transcriptional cdks phosphorylate the carboxy-terminal domain of RNA polymerase II, facilitating efficient transcriptional initiation and elongation. Inhibition of these cdks primarily affects the accumulation of transcripts with short half-lives, including those encoding antiapoptosis family members, cell cycle regulators, as well as p53 and nuclear factor-kappa B-responsive gene targets. These effects may account for apoptosis induced by cdk9 inhibitors, especially in malignant hematopoietic cells, and may also potentiate cytotoxicity mediated by disruption of a variety of pathways in many transformed cell types. Current work is focusing on overcoming pharmacokinetic barriers that hindered development of flavopiridol, a pan-cdk inhibitor, as well as assessing novel classes of compounds potently targeting groups of cell cycle cdks (cdk4/6 or cdk2/1) with variable effects on the transcriptional cdks 7 and 9. These efforts will establish whether the strategy of cdk inhibition is able to produce therapeutic benefit in the majority of human tumors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 810A,44 Binney St, Boston, MA 02115 USA. EM shapiro@dfci.harvard.edu FU NCI NIH HHS [P20 CA90578, R01 CA090687, R01 CA90687] NR 211 TC 551 Z9 570 U1 11 U2 74 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 APR 10 PY 2006 VL 24 IS 11 BP 1770 EP 1783 DI 10.1200/JCO.2005.03.7689 PG 14 WC Oncology SC Oncology GA 032OL UT WOS:000236783900017 PM 16603719 ER PT J AU Teng, YD Choi, H Huang, WZ Onario, RC Frontera, WR Snyder, EY Sabharwal, S AF Teng, YD Choi, H Huang, WZ Onario, RC Frontera, WR Snyder, EY Sabharwal, S TI Therapeutic effects of clenbuterol in a murine model of amyotrophic lateral sclerosis SO NEUROSCIENCE LETTERS LA English DT Article DE G93A-SOD1 transgenic mice; clenbuterol; spinal cord; amyotrophic lateral sclerosis; dimorphism ID GROWTH-FACTOR-BETA; SUPEROXIDE-DISMUTASE; MICE; RAT; STIMULATION; ISCHEMIA; DISEASE; INJURY AB We investigated the effects of clenbuterol, a beta 2-adrenoceptor agonist with known anabolic and neuroprotective properties, on G93A-SOD1 mice, a transgenic murine model of familial amyotrophic lateral sclerosis (ALS). Relative to saline-treated vehicle controls (0.2 ml/kg/day; i.p.), early pathologic G93A-SOD1 mice treated with clenbuterol (1.5 mg/kg/day; i.p.) demonstrated a delayed onset of hindlimb signs as measured by rotarod performance, slowed disease progression, as well as trends toward mitigated losses of lumbar motoneurons and body weight. Responses in female G93A-SOD1 mice were favorable to those of males, suggesting synergistic effects between clenbuterol and sex-specific factors. Overall, our data suggest that clenbuterol offers therapeutic effects on ALS-related neuromuscular degeneration. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Brigham & Womens Hosp,Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. VA Boston Healthcare Syst, SCI Res, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Teng, YD (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Brigham & Womens Hosp,Dept Neurosurg, 300 Longwood Ave,Bader 3, Boston, MA 02115 USA. EM yang_teng@hms.harvard.edu FU NINDS NIH HHS [R01 NS40822] NR 20 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 10 PY 2006 VL 397 IS 1-2 BP 155 EP 158 DI 10.1016/j.neulet.2005.12.007 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 025CA UT WOS:000236241700032 PM 16388902 ER PT J AU Walhovd, KB Fjell, AM Reinvang, I Lundervold, A Fischl, B Quinn, BT Makris, N Dale, AM AF Walhovd, KB Fjell, AM Reinvang, I Lundervold, A Fischl, B Quinn, BT Makris, N Dale, AM TI The functional and structural significance of the frontal shift in the old/new ERP effect SO BRAIN RESEARCH LA English DT Article DE cortex; ERP; MRI; memory; aging; old/new effect ID EVENT-RELATED POTENTIALS; AGE-RELATED-CHANGES; LONG-TERM-MEMORY; ADULT LIFE-SPAN; RECOGNITION MEMORY; BRAIN POTENTIALS; WORD REPETITION; OLDER-ADULTS; SCALP DISTRIBUTION; P300 AB There is a lack of studies mapping electrophysiological. event-related potentials (ERPs) to structural neuroanatomical characteristics. The aim of the present study was to integrate electrophysiological memory-related activity with cortical and hippocampal volume, as well as psychometric memory performance, in a life-span sample. More specifically, we wanted to investigate the functional significance of the often-observed frontal shift of ERP amplitude with increasing age and whether neuroanatomical characteristics can explain this shift. Sixty six healthy participants (20-78 years) went through a neuropsychological examination, MRI scans, and a visual recognition ERP task with verbal stimuli. The results showed that ERPs elicited in the recognition memory task (the old/new effect) correlated significantly with cortical volume, but not with hippocampal volume. Large cortex predicted more differentiated ERP activity and not just larger amplitude in general, implying more distinct and efficient retrieval. Furthermore, ERP amplitude, cortical volume, and hippocampal volume all predicted scores on a composite memory scale. All these relationship were dependent upon the common influence of age. Finally, the participants with the most anterior distribution of activity showed the poorest recognition memory performance. Neither cortical nor hippocampal volume were related to this frontal shift. it is concluded that the distribution of activity along the anterior-posterior axis in a memory paradigm may have functional but not neuroanatomical volumetric correlates. The functional correlates need not be restricted to the older age groups. (c) 2006 Published by Elsevier B.V. C1 Univ Oslo, Inst Psychol, N-0317 Oslo, Norway. Univ Oslo, Rikshosp, Dept Psychosomat Med, Oslo, Norway. Univ Bergen, Dept Physiol & Locus Neurosci, N-5020 Bergen, Norway. Harvard Univ, Massachusetts Gen Hosp, MGH, NMR Ctr, Charlestown, MA 02129 USA. MIT, Comp Sci & Artificial Intelligence Lab, Charlestown, MA 02129 USA. Harvard Univ, Ctr Morphomet Anal, MGH, Charlestown, MA 02129 USA. Norwegian Univ Sci & Technol, MR Ctr, Trondheim, Norway. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. RP Walhovd, KB (reprint author), Univ Oslo, Inst Psychol, PB 1094 Blindern, N-0317 Oslo, Norway. EM k.b.walhovd@psykologi.uio.no RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [R01-RR16594, P41-RR14075, R01-RR13609]; NINDS NIH HHS [R01-NS39581] NR 71 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 7 PY 2006 VL 1081 BP 156 EP 170 DI 10.1016/j.brainres.2006.01.076 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 036TQ UT WOS:000237098900019 PM 16542641 ER PT J AU Roozendaal, R Carroll, MC AF Roozendaal, R Carroll, MC TI Emerging patterns in complement-mediated pathogen recognition SO CELL LA English DT Review ID SPLENIC MARGINAL ZONE; INNATE IMMUNITY; B-CELL; RECEPTOR; MICE; MACROPHAGES; INFECTION; EVOLUTION; RESPONSES; PATHWAY AB Protection from acute infection requires an immediate response by the host innate immune system. Two recent Cell papers, including one in this issue, provide new insight into the role of the complement system in response to blood-borne pathogens. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu NR 18 TC 45 Z9 48 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 7 PY 2006 VL 125 IS 1 BP 29 EP 32 DI 10.1016/j.cell.2006.03.018 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 039NY UT WOS:000237314200011 PM 16615887 ER PT J AU Foster, LJ de Hoog, CL Zhang, YL Zhang, Y Xie, XH Mootha, VK Mann, M AF Foster, LJ de Hoog, CL Zhang, YL Zhang, Y Xie, XH Mootha, VK Mann, M TI A mammalian organelle map by protein correlation profiling SO CELL LA English DT Article ID LARGE-SCALE ANALYSIS; SUBCELLULAR-LOCALIZATION; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; GENE-EXPRESSION; GLOBAL ANALYSIS; YEAST; GENOMICS; CELLS; PROTEASOME AB Protein localization to membrane-enclosed organelles is a central feature of cellular organization. Using protein correlation profiling, we have mapped 1,404 proteins to ten subcellular locations in mouse liver, and these correspond with enzymatic assays, marker protein profiles, and confocal microscopy. These localizations allowed assessment of the specificity in published organellar proteomic inventories and demonstrate multiple locations for 39% of all organellar proteins. Integration of proteomic and genomic data enabled us to identify networks of coexpressed genes, cis-regulatory motifs, and putative transcriptional regulators involved in organelle biogenesis., Our analysis ties biochemistry, cell biology, and genomics into a common framework for organelle analysis. C1 Univ So Denmark, Dept Biochem & Mol Biol, CEBI, DK-5230 Odense, Denmark. Univ British Columbia, Dept Biochem & Mol Biol, Ctr Proteom, Vancouver, BC V6T 1Z4, Canada. Max Planck Inst Biochem, Dept Proteom & Signal Transduct, D-82152 Martinsried, Germany. Chinese Acad Sci, Beijing Inst Genom, Beijing 101300, Peoples R China. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Syst Biol, Boston, MA 02115 USA. RP Mann, M (reprint author), Univ So Denmark, Dept Biochem & Mol Biol, CEBI, Campusvej 55, DK-5230 Odense, Denmark. EM mmann@biochem.mpg.de RI Mann, Matthias/A-3454-2013 OI Mann, Matthias/0000-0003-1292-4799 NR 43 TC 335 Z9 345 U1 7 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 7 PY 2006 VL 125 IS 1 BP 187 EP 199 DI 10.1016/j.cell.2006.03.022 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 039NY UT WOS:000237314200023 PM 16615899 ER PT J AU Aglipay, JA Martin, SA Tawara, H Lee, SW Ouchi, T AF Aglipay, JA Martin, SA Tawara, H Lee, SW Ouchi, T TI ATM activation by ionizing radiation requires BRCA1-associated BAAT1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRAND BREAKS; TELANGIECTASIA MUTATED ATM; DNA-DAMAGE RESPONSE; BRCA1 PHOSPHORYLATION; OVARIAN-CANCER; DEPENDENT PHOSPHORYLATION; GENE BRCA1; PROTEIN; COMPLEX; KINASE AB ATM ( ataxia telangiectasia mutated) is required for the early response to DNA-damaging agents such as ionizing radiation (IR) that induce DNA double-strand breaks. Cells deficient in ATM are extremely sensitive to IR. It has been shown that IR induces immediate phosphorylation of ATM at Ser(1981), leading to catalytic activation of the protein. We recently isolated a novel BRCA1-associated protein, BAAT1 (BRCA1-associated protein required for ATM activation-1), by yeast two-hybrid screening and found that BAAT1 also binds to ATM, localizes to double-strand breaks, and is required for Ser(1981) phosphorylation of ATM. Small interfering RNA-mediated stable or transient reduction of BAAT1 resulted in decreased phosphorylation of both ATM at Ser(1981) and CHK2 at Thr(68). Treatment of BAAT1-depleted cells with okadaic acid greatly restored phosphorylation of ATM at Ser(1981), suggesting that BAAT1 is involved in the regulation of ATM phosphatase. Protein phosphatase 2A-mediated dephosphorylation of ATM was partially blocked by purified BAAT1 in vitro. Significantly, acute loss of BAAT1 resulted in increased p53, leading to apoptosis. These results demonstrate that DNA damage-induced ATM activation requires a coordinated assembly of BRCA1, BAAT1, and ATM. C1 NYU, Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. Massachusetts Gen Hosp, Harvard Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Ouchi, T (reprint author), NYU, Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,POB 1130, New York, NY 10029 USA. EM Toru.Ouchi@mssm.edu FU NCI NIH HHS [R01 CA078356, P01 CA80058, R01 CA08568, R01CA79892, R01CA90631, R24CA095823]; NIGMS NIH HHS [F31 GM64148-01] NR 41 TC 18 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 7 PY 2006 VL 281 IS 14 BP 9710 EP 9718 DI 10.1074/jbc.M510332200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027HB UT WOS:000236404700083 PM 16452482 ER PT J AU Greenberg, SM AF Greenberg, SM TI Research on stroke: Small vessels, big problems SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BLOOD-PRESSURE C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. FU NIA NIH HHS [R01 AG026484] NR 4 TC 73 Z9 76 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 6 PY 2006 VL 354 IS 14 BP 1451 EP 1453 DI 10.1056/NEJMp068043 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 029DP UT WOS:000236539000003 PM 16598043 ER PT J AU Antman, EM Morrow, DA McCabe, CH Murphy, SA Ruda, M Sadowski, Z Budaj, A Lopez-Sendon, JL Guneri, S Jiang, F White, HD Fox, KAA Braunwald, E AF Antman, EM Morrow, DA McCabe, CH Murphy, SA Ruda, M Sadowski, Z Budaj, A Lopez-Sendon, JL Guneri, S Jiang, F White, HD Fox, KAA Braunwald, E CA ExTRACT-TIMI 25 Investigators TI Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; EARLY INTRAVENOUS HEPARIN; MOLECULAR-WEIGHT HEPARIN; RANDOMIZED-TRIAL; THROMBOLYSIS; THERAPY; ASPIRIN; REPERFUSION; ALTEPLASE; STREPTOKINASE AB Background: Unfractionated heparin is often used as adjunctive therapy with fibrinolysis in patients with ST-elevation myocardial infarction. We compared a low-molecular-weight heparin, enoxaparin, with unfractionated heparin for this purpose. Methods: We randomly assigned 20,506 patients with ST-elevation myocardial infarction who were scheduled to undergo fibrinolysis to receive enoxaparin throughout the index hospitalization or weight-based unfractionated heparin for at least 48 hours. The primary efficacy end point was death or nonfatal recurrent myocardial infarction through 30 days. Results: The primary end point occurred in 12.0 percent of patients in the unfractionated heparin group and 9.9 percent of those in the enoxaparin group (17 percent reduction in relative risk, P < 0.001). Nonfatal reinfarction occurred in 4.5 percent of the patients receiving unfractionated heparin and 3.0 percent of those receiving enoxaparin (33 percent reduction in relative risk, P < 0.001); 7.5 percent of patients given unfractionated heparin died, as did 6.9 percent of those given enoxaparin (P=0.11). The composite of death, nonfatal reinfarction, or urgent revascularization occurred in 14.5 percent of patients given unfractionated heparin and 11.7 percent of those given enoxaparin (P < 0.001); major bleeding occurred in 1.4 percent and 2.1 percent, respectively (P < 0.001). The composite of death, nonfatal reinfarction, or nonfatal intracranial hemorrhage (a measure of net clinical benefit) occurred in 12.2 percent of patients given unfractionated heparin and 10.1 percent of those given enoxaparin (P < 0.001). Conclusions: In patients receiving fibrinolysis for ST-elevation myocardial infarction, treatment with enoxaparin throughout the index hospitalization is superior to treatment with unfractionated heparin for 48 hours but is associated with an increase in major bleeding episodes. These findings should be interpreted in the context of net clinical benefit. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Cardiol Res Ctr, Dept Emergency Cardiol, Moscow 121552, Russia. Natl Inst Cardiol, Warsaw, Poland. Grochowski Hosp, Postgrad Med Sch, Dept Cardiol, Warsaw, Poland. Hosp Univ La Paz, Madrid, Spain. Dokuz Eylul Univ, Izmir, Turkey. Sanofi Aventis, Int Clin Dev, Bridgewater, NJ USA. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Antman, EM (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu NR 24 TC 332 Z9 364 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 6 PY 2006 VL 354 IS 14 BP 1477 EP 1488 DI 10.1056/NEJMoa060898 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 029DP UT WOS:000236539000006 PM 16537665 ER PT J AU Musher, DM AF Musher, DM TI Pneumococcal vaccine - Direct and indirect ("herd") effects SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DAY-CARE-CENTERS; STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINE; CARRIAGE; EFFICACY C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Care Line, Houston, TX 77211 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Care Line, Houston, TX 77211 USA. NR 11 TC 54 Z9 55 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 6 PY 2006 VL 354 IS 14 BP 1522 EP 1524 DI 10.1056/NEJMe068038 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 029DP UT WOS:000236539000012 PM 16598050 ER PT J AU Samuels, JF Riddle, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Pinto, A Knowles, JA Piacentini, J Cannistraro, PA Cullen, B Bienvenu, OJ Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G AF Samuels, JF Riddle, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Pinto, A Knowles, JA Piacentini, J Cannistraro, PA Cullen, B Bienvenu, OJ Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G TI The OCD Collaborative Genetics Study: Methods and sample description SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE obsessive compulsive disorder; genetics; genetic linkage ID OBSESSIVE-COMPULSIVE DISORDER; COMPLEX SEGREGATION ANALYSIS; PEDIATRIC PROBANDS; EPIDEMIOLOGY; FAMILY; SUSCEPTIBILITY; SCHIZOPHRENIA; ASSOCIATION; RATIONALE; LINKAGE AB Results from twin and family studies suggest that obsessive-compulsive disorder (OCD) may be transmitted in families but, to date, genes for the disorder have not been identified. The OCD Collaborative Genetics Study (OCGS) is a six-site collaborative genetic linkage study of OCD. Specimens and blinded clinical data will be made available through the National Institute of Mental Health (NIMH) cell repository. In this initial report, we describe the methods of the study and present clinical characteristics of affected individuals for researchers interested in this valuable resource for genetic studies of OCD. The project clinically evaluated and collected blood specimens from 238 families containing 299 OCD-affected sibling pairs and their parents, and additional affected relative pairs, for a genome-wide linkage study. Of the 999 individuals interviewed to date, 624 were diagnosed with "definite" OCD. The mean age of subjects was 36 years (range 7-95). The majority of affected individuals (66%) were female. The mean age at onset of obsessive-compulsive symptoms was 9.5 years. Specific mood disorders, anxiety disorders, eating disorders, and skin picking were more prevalent in female cases, whereas ties, Tourette disorder, and alcohol dependence were more prevalent in male cases. Compared to "definite" cases of OCD,'probable' cases (n = 82) had, on average, later age at onset of obsessive-compulsive symptoms, lower severity score, and fewer numbers of different categories of obsessions and compulsions, and they were less likely to have received treatment for their symptoms. (c) 2006 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-181, Baltimore, MD 21287 USA. RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [R01 MH050214, R01 MH050214-09] NR 31 TC 50 Z9 50 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 5 PY 2006 VL 141B IS 3 BP 201 EP 207 DI 10.1002/ajmg.b.30224 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 031BL UT WOS:000236679000001 PM 16511842 ER PT J AU Giovannucci, E Liu, Y Rimm, EB Hollis, BW Fuchs, CS Stampfer, MJ Willett, WC AF Giovannucci, E Liu, Y Rimm, EB Hollis, BW Fuchs, CS Stampfer, MJ Willett, WC TI Prospective study of predictors of vitamin D status and cancer incidence and mortality in men SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MALE HEALTH-PROFESSIONALS; FOOD FREQUENCY QUESTIONNAIRE; MYELOID-LEUKEMIA CELLS; PROSTATE-CANCER; UNITED-STATES; SOLAR-RADIATION; D METABOLITES; COLON-CANCER; SUBSEQUENT DEVELOPMENT; ULTRAVIOLET-RADIATION AB Background: Vitamin D has potent anticancer properties, especially against digestive-system cancers. Many human studies have used geographic residence as a marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered multiple determinants of vitamin D exposure (dietary and supplementary vitamin D, skin pigmentation, adiposity, geographic residence, and leisure-time physical activity-to estimate sunlight exposure) in relation to cancer risk in the Health Professionals Follow-Up Study. Methods: Among 1095 men of this cohort, we quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D vertical bar 25(OH)D vertical bar level by use of a multiple linear regression model. We used results from the model to compute a predicted 25(OH)D level for each of 47800 men in the cohort based on these characteristics. We then prospectively examined this variable in relation to cancer risk with multivariable Cox proportional hazards models. Results: From 1986 through January 31, 2000, we documented 4286 incident cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer) and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L in predicted 25(OH)D level was associated with a 17% reduction in total cancer incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval vertical bar CI vertical bar 0.74 to 0.92), a 29% reduction in total cancer mortality (RR 0.71, 95% CI = 0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR = 0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758 per 100000 men in the bottom decile of predicted 25(OH)D and 674 per 100000 men for the top decile; these respective rates were 326 per 100000 and 277 per 100000 for total cancer mortality and 128 per 100000 and 78 per 100000 for digestive-system cancer mortality. Results were similar when we controlled further for body mass index or physical activity level. Conclusions: Low levels of vitamin D may be associated with increased cancer incidence and mortality in men, particularly for digestive-system cancers. The vitamin D supplementation necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500 IU/day. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.harvard.edu FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 49 TC 596 Z9 617 U1 3 U2 34 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 5 PY 2006 VL 98 IS 7 BP 451 EP 459 DI 10.1093/jnei/djj101 PG 9 WC Oncology SC Oncology GA 031WL UT WOS:000236735800012 PM 16595781 ER PT J AU Koutkia, P Eaton, K You, SM Breu, J Grinspoon, S AF Koutkia, P Eaton, K You, SM Breu, J Grinspoon, S TI Growth hormone secretion among HIV infected patients: effects of gender, race and fat distribution SO AIDS LA English DT Article DE growth hormone; HIV; gender; race; lipodystrophy; central adiposity ID BODY-COMPOSITION; FACTOR-I; GLUCOSE-METABOLISM; DEFICIENT ADULTS; GH DEFICIENCY; PLUS ARGININE; IGF-I; INSULIN; MEN; LIPODYSTROPHY AB Objective: To determine the effects of gender, race, and fat redistribution on growth hormone (GH) secretory patterns in HIV-infectecl patients. Design: We investigated GH responses to growth hormone releasing hormone (GHRH) + arginine stimulation testing in HIV-infected subjects with fat redistribution, comparing HIV-infected males (n=139) and females (n=25) to non HIV-infected male (n=25) and female (n=26) control subjects similar in age, body mass index and race. Methods: A standard GHRH + arginine stimulation test [GHRH 1 mu g/kg and arginine 0.5 g/kg (maximum dose 30 g)] was performed, and fat redistribution was assessed by anthropometry. Results: HIV-infected women had significantly higher peak GH in response to GHRH + arginine (36.4 +/- 7.3 versus 18.9 +/- 2.0 ng/ml; P=0.003) and GH area under curve (AUC) (2679 +/- 593 versus 1284 +/- 133 (mg-min)/dl, P<0.001) compared to HIV-infected men. Among men, a cutoff of 7.5 ng/ml for peak GH response on the GHRH + arginine test achieved good specificity and sensitivity and optimally separated the HIV and control groups (e.g., the failure rates were 37% versus 8%; P=0.004, respectively). Among women, no specific cutoff could be determined to separate the HIV-infected and control subjects. Non-Caucasians demonstrated a higher GH AUC response compared to Caucasians, among the HIV-infected male subjects. In stepwise regression modeling waist-to-hip ratio was most significantly related to peak GH in response to GHRH + arginine in HIV-infected men. Conclusions: HIV-infected men with fat redistribution have significantly reduced GH peak responses and increased failure rates to standardized GH stimulation testing in comparison to healthy male control subjects and to HIV-infected women of similar age and body mass index. GH secretion is related to gender and race in HIV-infected patients. (C) 2006 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neuroendocrine Unit, Boston, MA USA. MIT, Gen Clin Res Ctr, Cambridge, MA 02139 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01 DK063639] NR 32 TC 18 Z9 19 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 APR 4 PY 2006 VL 20 IS 6 BP 855 EP 862 DI 10.1097/01.aids.0000218549.85081.8f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 031OI UT WOS:000236713500008 PM 16549969 ER PT J AU Perlin, JB Pogach, LM AF Perlin, JB Pogach, LM TI Improving the outcomes of metabolic conditions: Managing momentum to overcome clinical inertia SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID HEALTH-CARE-SYSTEM; DIABETES CARE; QUALITY; PROVIDERS; TRIAL C1 Vet Affairs New Jersey Hlth Care Syst, E Orange, NJ 07018 USA. US Dept Vet Affairs, Vet Hlth Adm, Washington, DC 20420 USA. RP Pogach, LM (reprint author), Vet Affairs New Jersey Hlth Care Syst, 385 Tremont Ave, E Orange, NJ 07018 USA. EM leonard.pogach@med.va.gov NR 19 TC 13 Z9 13 U1 0 U2 0 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 APR 4 PY 2006 VL 144 IS 7 BP 525 EP 527 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 031DU UT WOS:000236685100008 PM 16585667 ER PT J AU Namekawa, SH Park, PJ Zhang, LF Shima, JE McCarrey, JR Griswold, MD Lee, JT AF Namekawa, SH Park, PJ Zhang, LF Shima, JE McCarrey, JR Griswold, MD Lee, JT TI Postmeiotic sex chromatin in the male germline of mice SO CURRENT BIOLOGY LA English DT Article ID X-CHROMOSOME INACTIVATION; HISTONE H2A; MOUSE; SPERMATOGENESIS; GENE; DNA; UBIQUITINATION; EVOLUTION; PROTEINS; DYNAMICS AB In mammals, the X and Y chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during prophase I in the male germline, but their status thereafter is currently unclear. An abundance of X-linked spermatogenesis genes has spawned the view that the X must be active [1-8]. On the other hand, the idea that the imprinted paternal X of the early embryo may be preinactivated by MSCI suggests that silencing may persist longer [9-12]. To clarify this issue, we establish a comprehensive X-expression profile during mouse spermatogenesis. Here, we discover that the X and Y occupy a novel compartment in the postmeiotic spermatid and adopt a non-Rabl configuration. We demonstrate that this postmeiotic sex chromatin (PMSC) persists throughout spermiogenesis into mature sperm and exhibits epigenetic similarity to the XY body. In the spermatid, 87% of X-linked genes remain suppressed postmeiotically, while autosomes are largely active. We conclude that chromosome-wide X silencing continues from meiosis to the end of spermiogenesis, and we discuss implications for proposed mechanisms of imprinted X-inactivation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. Childrens Hosp Informat Program, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Washington State Univ, Sch Mol Biosci, Ctr Reprod Biol, Pullman, WA 99164 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78249 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Zhang, Li-Feng/0000-0003-0917-0017 FU NICHD NIH HHS [HD10808, HD46637]; NIGMS NIH HHS [GM58839, GM67825] NR 35 TC 232 Z9 239 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 4 PY 2006 VL 16 IS 7 BP 660 EP 667 DI 10.1016/j.cub.2006.01.066 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 030QM UT WOS:000236649400023 PM 16581510 ER PT J AU Jaffer, FA Libby, P Weissleder, R AF Jaffer, FA Libby, P Weissleder, R TI Molecular and cellular imaging of atherosclerosis - Emerging applications SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID ULTRASMALL SUPERPARAMAGNETIC PARTICLES; OXIDATION-SPECIFIC ANTIBODIES; POSITRON-EMISSION-TOMOGRAPHY; RISK-ASSESSMENT STRATEGIES; ACUTE CORONARY SYNDROMES; LOW-DENSITY-LIPOPROTEIN; IN-VIVO DETECTION; VULNERABLE PLAQUE; CONTRAST AGENT; IRON-OXIDE AB Molecular imaging studies have shed light on important biological aspects of atherosclerosis, and are now entering the clinical arena for the detection of clinical atheroma. This review first discusses fundamental principles regarding the rationale for and development of molecular imaging technologies for investigating atherosclerosis. Next, we highlight clinically promising imaging strategies that illuminate key biological aspects of atherosclerosis, including macrophage activity, protease activity, lipoprotein presence, apoptosis, and angiogenesis. We envision that several molecular imaging approaches will become important adjuncts to the clinical management of high-risk atherosclerosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), MGH CMIR, 149 13th St,Room 5406, Charlestown, MA 02129 USA. EM fjaffer@partners.org OI Jaffer, Farouc/0000-0001-7980-384X FU NHLBI NIH HHS [UO1-HL080731, R01 HL078641] NR 107 TC 127 Z9 135 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 4 PY 2006 VL 47 IS 7 BP 1328 EP 1338 DI 10.1016/j.jacc.2006.01.029 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 030PQ UT WOS:000236647200002 PM 16580517 ER PT J AU Mansour, M AF Mansour, M TI Highest dominant frequencies in atrial fibrillation - A new target for ablation? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID ISOLATED SHEEP HEART; MOTHER ROTORS; MECHANISM; EFFICACY; GRADIENT; HUMANS C1 Harvard Univ, Cardiac Arrhythmia Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Cardiac Arrhythmia Unit, Sch Med, Massachusetts Gen Hosp, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 18 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 APR 4 PY 2006 VL 47 IS 7 BP 1408 EP 1409 DI 10.1016/j.jacc.2006.01.032 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 030PQ UT WOS:000236647200014 PM 16580529 ER PT J AU Lewis, GD Witzke, C Colon-Hernandez, P Guerrero, JL Bloch, KD Semigran, MJ AF Lewis, GD Witzke, C Colon-Hernandez, P Guerrero, JL Bloch, KD Semigran, MJ TI Sildenafil improves coronary artery patency in a canine model of platelet-mediated cyclic coronary occlusion after thrombolysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NUCLEOTIDE PHOSPHODIESTERASE ISOZYMES; ACUTE MYOCARDIAL-INFARCTION; DEPENDENT PROTEIN-KINASE; GLYCOPROTEIN-IIB/IIIA; PLASMINOGEN-ACTIVATOR; THROMBIN INHIBITOR; IN-VITRO; VIAGRA; REOCCLUSION; TIROFIBAN AB OBJECTIVES We sought to assess the effect of sildenafil, a highly-specific type 5 phosphodiesterase (PDE5) inhibitor, on platelet-mediated cyclic coronary flow reductions occurring in a canine model of coronary thrombosis despite aspirin therapy. BACKGROUND The PDE5 inhibitors augment the antithrombotic effects of nitric oxide in vitro and in vivo, but it has been proposed that the PDES inhibitor sildenafil is prothrombotic. METHODS Cyclic coronary flow reductions were induced in the left anterior descending coronary artery by creation of a stenosis, endothehal injury, and thrombus formation followed by treatment with aspirin, heparin, and tissue plasminogen activator. After an initial observation period, dogs were treated with or without sildenafil (100 mu g/kg bolus followed by 4 mu g/kg/min infusion). RESULTS Cyclic coronary flow reductions ceased in five of six animals 18 +/- 5 min after initiation of sildenafil but continued in all six control animals. The portion of the observation period during which the coronary artery was patent increased from 52 +/- 9% to 83 +/- 5% after sildenafil administration (p = 0.008) but did not differ between the first and second observation periods in untreated dogs (49 +/- 11% vs. 44 +/- 11%, respectively). Among animals with plasma free sildenafil levels >= 20 nmol/l, cyclic coronary flow reductions were 73 +/- 12% less frequent and the time to cessation of cycling 72 +/- 14% shorter than in animals with levels < 20 nmol/1 (p < 0.05 for both). Sildenafil transiently decreased blood pressure 7 +/- 1% but did not change heart rate. Sildenafil treatment reduced ex vivo thrombin-induced platelet aggregation by 39 +/- 3% (p < 0.005). CONCLUSIONS Sildenafil improves coronary patency in a canine model of platelet-mediated coronary artery thrombosis, likely via inhibition of platelet aggregation. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 FU NHLBI NIH HHS [HL-04021, HL-70896] NR 39 TC 10 Z9 10 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 APR 4 PY 2006 VL 47 IS 7 BP 1471 EP 1477 DI 10.1016/j.jacc.2005.11.060 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 030PQ UT WOS:000236647200024 PM 16580539 ER PT J AU Stremlau, M Perron, M Lee, M Li, Y Song, B Javanbakht, H Diaz-Griffero, F Anderson, DJ Sundquist, WI Sodroski, J AF Stremlau, M Perron, M Lee, M Li, Y Song, B Javanbakht, H Diaz-Griffero, F Anderson, DJ Sundquist, WI Sodroski, J TI Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5 alpha restriction factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B30.2(SPRY) domain; tripartite motif; HIV-1; RING, B-box, and coiled-coil protein; innate immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE TRANSCRIPTION COMPLEXES; MURINE LEUKEMIA-VIRUS; CYCLOPHILIN-A; SIMIAN CELLS; OLD-WORLD; POSTENTRY RESTRICTION; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; HIV-1 VIRIONS AB The host restriction factor TRIM5 alpha mediates species-specific, early blocks to retrovirus infection; susceptibility to these blocks is determined by viral capsid sequences. Here we demonstrate that TRIM5 alpha variants from Old World monkeys specifically associate with the HIV type 1 (HIV-1) capsid and that this interaction depends on the TRIM5 alpha B30.2 domain. Human and New World monkey TRIM5 alpha proteins associated less efficiently with the HIV-1 capsid, accounting for the lack of restriction in cells of these species. After infection, the expression of a restricting TRIM5 alpha in the target cells correlated with a decrease in the amount of particulate capsid in the cytosol. In some cases, this loss of particulate capsid was accompanied by a detectable increase in soluble capsid protein. Inhibiting the proteasome did not abrogate restriction. Thus, TRIM5 alpha restricts retroviral infection by specifically recognizing the capsid and promoting its rapid, premature disassembly. C1 Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Utah, Dept Biochem, Salt Lake City, UT 84132 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Yuan/B-4098-2013 FU NHLBI NIH HHS [HL 54785, P50 HL054785]; NIAID NIH HHS [AI 45405, AI 063987, AI 28691, P30 AI028691, R01 AI045405, R01 AI063987, R37 AI045405] NR 59 TC 441 Z9 457 U1 3 U2 29 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 4 PY 2006 VL 103 IS 14 BP 5514 EP 5519 DI 10.1073/pnas.0509996103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 030LP UT WOS:000236636400050 PM 16540544 ER PT J AU Demirci, U AF Demirci, U TI Droplet-based photoresist deposition SO APPLIED PHYSICS LETTERS LA English DT Article ID EJECTOR ARRAYS; POLYMERS; WALL AB Photoresist droplets are ejected onto a wafer surface by an acoustic two-dimensional micromachined ejector array. The spread of single droplets on a silicon wafer surface at varying droplet speeds is studied. Series of photoresist droplets are printed periodically drop on demand on a silicon wafer surface and profiles of a single droplet and two droplets overlapping with varying distances of 25 and 1 mu m on a silicon wafer are demonstrated. Moreover, 3.4 mu m thick spinless full coverage of a 4 in. wafer with photoresist is demonstrated which indicates a potential for coating wafers in less than a few seconds. (c) 2006 American Institute of Physics. C1 Stanford Univ, Edward L Ginzton Lab, Dept Elect Engn, Stanford, CA 94305 USA. RP Demirci, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,BioMEMS Resource Ctr, Charlestown, MA 02129 USA. EM utkan@stanfordalumni.org NR 16 TC 6 Z9 6 U1 2 U2 6 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD APR 3 PY 2006 VL 88 IS 14 AR 144104 DI 10.1063/1.2191087 PG 3 WC Physics, Applied SC Physics GA 030CX UT WOS:000236612000121 ER PT J AU Trivedi, MA Coover, GD AF Trivedi, MA Coover, GD TI Neurotoxic lesions of the dorsal and ventral hippocampus impair acquisition and expression of trace-conditioned fear-potentiated startle in rats SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Behavioral-Neuroscience-Society CY JUN 16-20, 2004 CL Key West, FL SP Int Behav Neurosci Soc DE startle; trace conditioning; fear; ventral hippocampus; dorsal hippocampus ID MEDIAL PREFRONTAL CORTEX; NICTITATING-MEMBRANE RESPONSE; LONG-TERM POTENTIATION; CONTEXTUAL FEAR; INHIBITORY AVOIDANCE; MEMORY; DELAY; AMYGDALA; ANXIETY; RABBITS AB Pavlovian delay conditioning, in which a conditioned stimulus (CS) and unconditioned stimulus (US) co-terminate, is thought to reflect nondeclarative memory. In contrast, trace conditioning, in which the CS and US are temporally separate, is thought to reflect declarative memory. Hippocampal lesions impair acquisition and expression of trace conditioning measured by the conditioned freezing and eyeblink responses, while having little effect on the acquisition of delay conditioning. Recent evidence suggests that lesions of the ventral hippocampus (VH) impair conditioned fear under conditions in which dorsal hippocampal (DH) lesions have little effect. In the present study, we examined the time-course of fear expression after delay and trace conditioning using the fear-potentiated startle (FPS) reflex, and the effects of pre- and post-training lesions to the VH and DH on trace-conditioned FPS. We found that both delay- and trace-conditioned rats displayed significant FPS near the end of the CS relative to the unpaired control group. In contrast, trace-conditioned rats displayed significant FPS throughout the duration of the trace interval, whereas FPS decayed rapidly to baseline after CS offset in delay-conditioned rats. In experiment 2, both DH and VH lesions were found to significantly reduce the overall magnitude of FPS compared to the control group, however, no differences were found between the DH and VH groups. These findings support a role for both the DH and VH in trace fear conditioning, and suggest that the greater effect of VH lesions on conditioned fear might be specific to certain measures of fear. (c) 2005 Elsevier B.V. All rights reserved. C1 No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. RP Trivedi, MA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace 11G,GRECC, Madison, WI 53705 USA. EM mt2@medicine.wisc.edu NR 65 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 3 PY 2006 VL 168 IS 2 BP 289 EP 298 DI 10.1016/j.bbr.2005.11.029 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 018JT UT WOS:000235761200015 PM 16413066 ER PT J AU Kabrhel, C McAfee, AT Goldhaber, SZ AF Kabrhel, C McAfee, AT Goldhaber, SZ TI The probability of pulmonary embolism is a function of the diagnoses considered most likely before testing SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE pulmonary embolism; venous thromboembolism; pretest probability; diagnosis ID EMERGENCY-DEPARTMENT PATIENTS; D-DIMER; ANGIOGRAPHY; RULE AB Objectives: To determine the frequency of pulmonary embolism (PE) diagnosis when different alternative diagnoses were considered most likely before testing, because the relationship between specific alternative diagnoses and the diagnosis of PE has not been explored. Methods: This study was a preplanned secondary analysis of a prospective study of the diagnosis of pulmonary embolism conducted in the emergency department (ED) of an urban university hospital. Physicians were queried as to their most likely pretest diagnosis when they ordered any of the following tests to evaluate possible PE: D-dimer, contrast-enhanced computed tomography of the chest, ventilation-perfusion lung scan, or pulmonary angiogram. To compare the frequency of PE diagnosis across alternative diagnoses, risk ratios, 95% confidence intervals (CI), and p-values using Fisher's exact test were calculated. Results: Six hundred seven patients were enrolled, and 61 had PE. Physicians thought PE was the most likely pretest diagnosis in 162 (26.7%) patients, and 20.4% (95% CI = 14.4% to 27.4%) of these patients had PE. For four alternative diagnoses, PE was diagnosed less frequently than when PE was considered most likely: rnusculoskeletal pain (2.2%, 95% CI = 0.4% to 6.2%), anxiety (1.7%, 95% CI = 0.0 to 9.2%), asthma or chronic obstructive pulmonary disease (0, 95% CI = 0.0 to 10.9%), and viral syndrome (0, 95% CI = 0.0 to 14.31%). Conclusions: The frequency of PE is related to the most likely pretest alternative diagnosis. PE is diagnosed infrequently when anxiety, asthma or chronic obstructive pulmonary disease, musculoskeletal pain, or viral syndrome is the most likely alternative diagnosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. i3 Magnifi, Auburndale, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Kabrhel, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 55 Fruit St,115 Clin Bldg, Boston, MA 02114 USA. EM ckabrhel@partners.org NR 10 TC 8 Z9 8 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2006 VL 13 IS 4 BP 471 EP 474 AR PII ISSN 1069-6563583 DI 10.1197/j.aem.2005.11.077 PG 4 WC Emergency Medicine SC Emergency Medicine GA 028SH UT WOS:000236508600022 PM 16531604 ER PT J AU Li, G Papannagari, R DeFrate, LE Yoo, JD Park, SE Gill, TJ AF Li, G Papannagari, R DeFrate, LE Yoo, JD Park, SE Gill, TJ TI Comparison of the ACL and ACL graft forces before and after ACL reconstruction - An in-vitro robotic investigation SO ACTA ORTHOPAEDICA LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; PATELLAR LIGAMENT; KNEE KINEMATICS; SITU FORCES; TENDON; AUTOGRAFTS; PLACEMENT; FIXATION; ROTATION; TENSION AB Background Long-term follow-up studies have indicated that there is an increased incidence of arthrosis following anterior cruciate ligament (ACL) reconstruction, suggesting that the reconstruction may not reproduce intact ACL biomechanics. We studied not only the magnitude but also the orientation of the ACL and ACL graft forces. Methods 10 knee specimens were tested on a robotic testing system with the ACL intact, deficient, and reconstructed (using a bone-patella tendon-bone graft). The magnitude and orientation of the ACL and ACL graft forces were determined under an anterior tibial load of 130 N at full extension, and 15, 30, 60, and 90 degrees of flexion. Orientation was described using elevation angle (the angle formed with the tibial plateau in the sagittal plane) and deviation angle (the angle formed with respect to the anteroposterior direction in the transverse plane). Results ACL reconstruction restored anterior fibial translation to within 2.6 mm of that of the intact knee under the 130-N anterior load. Average internal tibial rotation was reduced after ACL reconstruction at all flexion angles. The force vector of the ACL graft was significantly different from the ACL force vector. The average values of the elevation and deviation angles of the ACL graft forces were higher than that of the intact ACL at all flexion angles. Interpretation Contemporary single bundle ACL reconstruction restores anterior fibial translation under anterior tibial load with different forces (both magnitude and orientation) in the graft compared to the intact ACL. Such graft function might alter knee kinematics in other degrees of freedom and could overly constrain the tibial rotation. An anatomic ACL reconstruction should reproduce the magnitude and orientation of the intact ACL force vector, so that the 6-degrees-of-freedom knee kinematics and joint reaction forces can be restored. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg,Bioengn Lab, Boston, MA 02115 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. Ewha Univ, Mokdong Hosp, Dept Orthoped Surg, Seoul, South Korea. Dongguk Univ Int Hosp, Dept Orthopaed Surg, Seoul, South Korea. RP Gill, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthoped Surg,Bioengn Lab, Boston, MA 02115 USA. EM gli1@partners.org NR 28 TC 34 Z9 35 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1745-3674 J9 ACTA ORTHOP JI Acta Orthop. PD APR PY 2006 VL 77 IS 2 BP 267 EP 274 DI 10.1080/17453670610046019 PG 8 WC Orthopedics SC Orthopedics GA 047PE UT WOS:000237890400013 PM 16752289 ER PT J AU Loberg, EM Jorgensen, HA Green, MF Rund, BR Lund, A Diseth, A Oie, M Hugdahl, K AF Loberg, EM Jorgensen, HA Green, MF Rund, BR Lund, A Diseth, A Oie, M Hugdahl, K TI Positive symptoms and duration of illness predict functional laterality and attention modulation in schizophrenia SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE attention; dichotic listening tests; laterality; schizophrenia; symptoms ID TRANSCRANIAL MAGNETIC STIMULATION; DICHOTIC-LISTENING PERFORMANCE; SUPERIOR TEMPORAL GYRUS; AUDITORY VERBAL HALLUCINATIONS; POSITRON EMISSION TOMOGRAPHY; LEFT TEMPOROPARIETAL CORTEX; FORMAL THOUGHT-DISORDER; CEREBRAL BLOOD-FLOW; GRAY-MATTER VOLUME; HOMO-SAPIENS PAYS AB Objective: Dichotic listening (DL) performance in schizophrenia. reflecting hemispheric asymmetry and the functional integrity of the left temporal lobe, can vary with clinical characteristics. Previous studies have not taken the co-linearity of clinical variables into account. The aim of the present study was to evaluate the roles of positive symptoms and duration of illness in DL through structural Equation Modeling (SEM), thus allowing for complex relationships between the variables. Method: We pooled patients from four previous DL Studies to create a heterogeneous group Of 129 schizophrenic patients, all tested with a consonant-vowel syllables DL procedure that Included attentional Instructions. Results: A model where positive symptoms predicted a laterality component and duration of illness predicted an attention component in DL was confirmed. Conclusion: Positive symptoms predicted reduced functional laterality, suggesting involvement or left temporal lobe language processing. Duration of illness predicted impaired attention modulation. possibly reflecting the Involvement of frontotemporal networks. C1 Univ Bergen, Dept Psychiat, Bergen Mental Hlth Res Ctr, N-5035 Bergen, Norway. Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway. Univ Calif Los Angeles, Inst Neuropsychiat, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Oslo, Inst Psychol, Oslo, Norway. Univ Bergen, Dept Psychosocial Sci, Bergen, Norway. Oppland Hosp, Child & Adolescent Psychiat Outpatient Clin, Lillehammer, Norway. RP Loberg, EM (reprint author), Univ Bergen, Dept Psychiat, Bergen Mental Hlth Res Ctr, N-5035 Bergen, Norway. EM else.marie.loeberg@psych.uib.no NR 90 TC 20 Z9 20 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 2006 VL 113 IS 4 BP 322 EP 331 DI 10.1111/j.1600-0447.2005.00627.x PG 10 WC Psychiatry SC Psychiatry GA 028GK UT WOS:000236474800010 PM 16638077 ER PT J AU Krahn, D Grossman, J Henk, H Mussey, M Crosby, R Gosnell, B AF Krahn, D Grossman, J Henk, H Mussey, M Crosby, R Gosnell, B TI Sweet intake, sweet-liking, urges to eat, and weight change: Relationship to alcohol dependence and abstinence SO ADDICTIVE BEHAVIORS LA English DT Article DE sweet-liking; alcohol; dependence; abstinence; diet; urges ID RATS; PREFERENCE; ETHANOL; DEPRIVATION; CONSUMPTION; LINES AB Introduction: Linkages between alcohol dependence (AD) and abstinence and aspects of food ingestion and preference have been described in animals and humans, including (1) eating sweets decreases urges to drink alcohol; (2) preferences for highly sweet tastants is associated with alcohol dependence; and (3) food deprivation leads to increased alcohol intake. Methods: We randomly assigned AD subjects in early abstinence to 3 different sets of dietary instructions (eat sweets for alcohol urges; eat a balanced diet; avoid sweets). We compared the groups on urges for alcohol, alcohol consumption, weight, and sweet preference at baseline, one, and six months. We also compared these AD subjects with light-drinking C's and compared AD subjects who remained abstinent for 6 month follow-up with nonabstinent AD subjects. Results: Recruited AS subjects, 38 of 68, completed 6 month follow-up; 27 of 36 C's completed the follow-up. 21 AD's were abstinent while 17 were non-abstinent. There was no effect of dietary recommendations on urges to drink or alcohol consumption. AD's were more likely than C's to prefer highly sweet tastants. The proportion of AD's preferring the sweetest tastant decreased over time. AD's gained more weight than C's over the 6-month follow-up. Discussion: While the use of sweets did not affect urges to drink or drinking, important relationships between sweet preference, weight gain, and alcohol dependence or abstinence were identified. (c) 2005 Elsevier Ltd. All rights reserved. C1 William S Middleton Mem Vet Adm Med Ctr, Psychiat Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI USA. NRI, Fargo, ND USA. RP Krahn, D (reprint author), William S Middleton Mem Vet Adm Med Ctr, Psychiat Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. EM dean.krahn@med.va.gov OI Crosby, Ross/0000-0001-9131-1629 NR 30 TC 24 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2006 VL 31 IS 4 BP 622 EP 631 DI 10.1016/j.addbeh.2005.05.056 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 032BQ UT WOS:000236749300006 PM 15990241 ER PT J AU Moller, CC Pollak, MR Reiser, J AF Moller, CC Pollak, MR Reiser, J TI The genetic basis of human glomerular disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE hereditary diseases; glomerulonephritis; nephrotic syndrome; proteinuria; podocytes ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; SLIT DIAPHRAGM; MUTATION; DEFICIENCY; TRPC6; FSGS AB Clinical and molecular research aimed to understand glomerular disease has emerged to one of the most active areas in renal research at large. The unraveling of genetic causes resulting in proteinuria has helped to define roles for each component of the glomerular filtration barrier in the development of urinary protein loss. Although most of the inherited glomerular diseases have in common defects in the podocyte, the glomerular basement membrane is also of critical importance for normal kidney permselectivity. This review summarizes recent progress in the eludication of genetic causes of glomerular disease and discusses their implications for the understanding of the pathogenic mechanisms, which can lead to disruption of the glomerular filtration barrier. (c) 2006 by the National Kidney Foundation, Inc. C1 Brigham & Womens Hosp, Div Renal, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. RP Reiser, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, MGH E CNY-149-8230,149 13th St, Charlestown, MA 02129 USA. EM jreiser@partners.org NR 17 TC 14 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2006 VL 13 IS 2 BP 166 EP 173 DI 10.1053/j.ackd.2006.01.009 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 032JC UT WOS:000236769700012 PM 16580618 ER PT J AU Humbert, M Dietrich, U AF Humbert, Michael Dietrich, Ursula TI The role of neutralizing antibodies in HIV infection SO AIDS REVIEWS LA English DT Review DE HIV; neutralizing antibodies; immunogens; vaccination ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; LONG-TERM NONPROGRESSORS; RECOMBINANT GLYCOPROTEIN-120 VACCINE; DEPENDENT CELLULAR CYTOTOXICITY; BLOOD MONONUCLEAR-CELLS; ENVELOPE GLYCOPROTEIN; IN-VITRO; NONNEUTRALIZING ANTIBODIES; ANTIRETROVIRAL THERAPY AB Neutralizing antibodies against HIM play an important role in preventing viral infections. Less clear is their role in the containment of viral replication in infected individuals. However, evidence is accumulating that neutralizing antibodies may help the cellular arm of the immune response to prevent or delay the progression to AIDS. Detection of neutralizing antibodies depends on the in vitro neutralization assays used, and standardization of the assays is essential in order to be able to compare the magnitude and quality of a neutralizing antibody response in sera or other fluids from HIV-infected patients, uninfected HIM exposed persons, or vaccinated animals/persons. Viral mechanisms to prevent neutralization include high variability and extensive glycosylation of the Envelope proteins, Envelope trimerization and shedding as well as late exposure of functionally important entry domains by conformational changes induced upon CD4 binding. These are also the difficulties encountered in the design of immunogens able to induce neutralizing antibodies upon vaccination. C1 Biomed Res Inst, Frankfurt, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Dietrich, U (reprint author), Georg Speyer Haus,Paul Ehrlich Str 42-44, D-60596 Frankfurt, Germany. EM ursula.dietrich@em.uni-frankfurt.de NR 95 TC 26 Z9 27 U1 0 U2 2 PU PERMANYER PUBLICATIONS PI BARCELONA PA MALLORCA, 310, BARCELONA, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD APR-JUN PY 2006 VL 8 IS 2 BP 51 EP 59 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 060JQ UT WOS:000238798900001 PM 16848273 ER PT J AU Sonnenberg, A AF Sonnenberg, A TI Personal view: the paradox of runaway competitions in gastroenterology SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SYSTEMATIC REVIEWS; HEALTH; CARE AB Occasionally, gastroenterologists harbour reservations about the appropriateness of various procedures and management options, yet find themselves drawn into a competition and forced by outside exigencies to provide such services. The aim of the present analysis was to describe patterns of runaway competitions and factors that influence their occurrence in gastroenterology. The interactions between two physicians or physician and patient are modelled as non-zero-sum games of two players. The outcomes associated with two behavioural strategies of two players are arranged in a two-by-two game matrix. Many scenarios of clinical gastroenterology and social interactions among gastroenterologists are characterized by the underlying game of prisoner's dilemma, where two players can choose to co-operate or compete with each other. Although from their joint perspective co-operation results in a higher joint utility, the perspective of each individual favours competition. Following the inescapable logic of their individual perspective, the players end up with a worse outcome than through co-operation. A runaway competition ensues if the game is played repeatedly with players successively increasing their stakes. Ultimately, each player tries to outdo the opponent while heading in the wrong direction. Recognizing the hallmarks of the game of prisoner's dilemma may help gastroenterologists to avoid such competitions. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM sonnenbe@ohsu.edu NR 15 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR 1 PY 2006 VL 23 IS 7 BP 871 EP 878 DI 10.1111/j.1365-2036.2006.02833.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 022PS UT WOS:000236068700003 PM 16573789 ER PT J AU Lee, JG Lum, D Urayama, S Mann, S Saavedra, S Vigil, H Vilaysak, C Leung, JW Leung, FW AF Lee, JG Lum, D Urayama, S Mann, S Saavedra, S Vigil, H Vilaysak, C Leung, JW Leung, FW TI Extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening: a pilot study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; GASTROINTESTINAL ENDOSCOPY; CONSCIOUS SEDATION; ASYMPTOMATIC ADULTS; SELECTIVE SEDATION; COMPLICATIONS; INSERTION AB Background Caecal intubation can be achieved by extended flexible sigmoidoscopy in 32% of patients. Aim To assess the feasibility of extended flexible sigmoidoscopy performed by colonoscopists for colorectal cancer screening. Methods We enrolled 41 patients referred for screening flexible sigmoidoscopy. After purging, examination was performed with a colonoscope. All patients completed sigmoidoscopy (success in meeting referral goal); 93% and 71% had examination to the transverse or ascending colon, and caecum, respectively. Overall yield and right-sided polyps was 56% and 27%, respectively. Caecal intubation and complete examination with polypectomy took 6.0 +/- 2.5 and 18.3 +/- 5.1 min, respectively; with no complications. Twelve patients requested colonoscope withdrawal because of discomfort. Although 46% reported moderate to severe discomfort, 39% and 36%, respectively, were definitely or probably willing to repeat flexible sigmoidoscopy. Results Unsedated colonoscopy introduced as extended flexible sigmoidoscopy emphasizes the benefits of added yield rather than the negative image of withholding of discomfort relief. The patient can choose to accept the equivalent of an unsedated colonoscopy or reject the option based on perceived discomfort during extended flexible sigmoidoscopy performed by the colonoscopist. Conclusion Extended flexible sigmoidoscopy is a feasible option in carefully selected patients, fully prepared and by an experienced colonoscopist. C1 Univ Calif Davis, Med Ctr, Res & Med Serv, Sacramento, CA 95817 USA. Univ Calif Davis, Med Ctr, Vet Affairs No Calif Hlth Care Syst, Sacramento, CA 95817 USA. Sepulveda Ambulatory Care Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Leung, FW (reprint author), VA Sepulveda Ambulatory Care Ctr & Nursing Home, Div Gastroenterol, 16111 Plummer St,111G, Sepulveda, CA 91343 USA. EM felix.leung@med.va.gov NR 42 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR 1 PY 2006 VL 23 IS 7 BP 945 EP 951 DI 10.1111/j.1365-2036.2006.02838.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 022PS UT WOS:000236068700011 PM 16573797 ER PT J AU Reynolds, HR Anand, SK Fox, JM Harkness, S Dzavik, V White, HD Webb, JG Gin, K Hochman, JS Picard, MH AF Reynolds, HR Anand, SK Fox, JM Harkness, S Dzavik, V White, HD Webb, JG Gin, K Hochman, JS Picard, MH TI Restrictive physiology in cardiogenic shock: Observations from echocardiography SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR DIASTOLIC FUNCTION; MITRAL DECELERATION TIME; CAPILLARY WEDGE PRESSURE; PROGNOSTIC IMPLICATIONS; DOPPLER-ECHOCARDIOGRAPHY; EARLY REVASCULARIZATION; STRONG PREDICTOR; MORTALITY; VELOCITY AB Background: Left ventricular diastolic abnormalities are associated with adverse outcome in myocardial inforction. Intra-aortic balloon pump (IABP) support is associated with improved diastolic filling. In the SHOCK trial and registry, average left ventricular ejection fraction (LVEF) was approximately 30%, higher than expected based on the classic paradigm. We hypothesized that restrictive physiology plays a role in cardiogenic shock (CS). Methods: Echocardiograms obtained during the SHOCK trial within 24 hours of randomization were centrally interpreted. Patients with quantifiable mitral E-wave deceleration time were included (n = 64). The restrictive filling pattern was defined as deceleration time < 140 milliseconds. Results: The restrictive pattern was seen in 60.9% of patients studied. Patients with this pattern had lower LVEF (31.1% vs 39.0%, P = .02) and higher wall motion score index (2.1 vs 1.8, P = .05). Patients with restriction were more likely to have IABP support during echocardiography (73.7% vs 43.5%, P = .03). There was no difference with and without restriction in demographic and hemodynamic variables or in mitral regurgitation degree or extent of coronary disease. The restrictive pattern had positive predictive value of 80% for pulmonary, capillary wedge pressure >= 20 mm Hg. Thirty-day survival was 53.9% with restriction versus 68.0% without restriction, P = .31. There was no difference in New York Heart Association class at 1 year between groups. Conclusions: The restrictive filling pattern is common in patients with CS, which may suggest that diastolic dysfunction contributes to CS pathogenesis. Patients with the restrictive pattern had lower LVEF despite IABP support. An association between the restrictive pattern and mortality was not demonstrated; power was limited by sample size. C1 NYU, Sch Med, Dept Med, New York, NY USA. New England Res Inst, Watertown, MA 02172 USA. Univ Hlth Network, Toronto, ON, Canada. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Vancouver Hosp, Vancouver, BC, Canada. RP Reynolds, HR (reprint author), 550 1st Ave,Room HCC 1170, New York, NY 10016 USA. EM harmony.raynolds@nyumc.org RI Reynolds, Harmony/M-4818-2013; OI Reynolds, Harmony/0000-0003-0284-0655; Picard, Michael/0000-0002-9264-3243; Hochman, Judith/0000-0002-5889-5981 NR 22 TC 5 Z9 6 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD APR PY 2006 VL 151 IS 4 AR e15 DI 10.1016/j.ahj.2005.08.020 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 031RF UT WOS:000236721000030 ER PT J AU Rodrigues, ACT Costa, JD Alves, GB da Silva, DF Picard, MH Andrade, JL Mathias, W Negrao, CE AF Rodrigues, ACT Costa, JD Alves, GB da Silva, DF Picard, MH Andrade, JL Mathias, W Negrao, CE TI Left ventricular function after exercise training in young men SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEART-FAILURE; ECHOCARDIOGRAPHY; DIMENSIONS AB The effects of endurance training have been extensively studied in athletes, but longitudinal studies of exercise-induced cardiac changes in normal patients are limited. To assess the effects of 6 months of moderate-intensity aerobic training (1 hour/day, 3 times/week) on normal hearts, 23 sedentary men aged 31.1 +/- 3.5 years were studied by standard and tissue Doppler echocardiography. Left ventricular (LV) systolic function was assessed by the ejection fraction and Doppler-measured stroke volume, and diastolic function was assessed by transmitral and pulmonary venous flow. Tissue Doppler systolic (Sm), early (Em), and late (Am) myocardial velocities were obtained at the septal and lateral mitral annulus. After training, there was a 14.5% increase in peak oxygen consumption (p = 0.000002) and a decrease in heart rate (60 +/- 7 to 56 +/- 8 beats/min, p = 0.01). Septal and posterior wall thickness increased (8.7 +/- +/- 1.0 to 9.4 +/- 1.3 mm, p = 0.002, and 8.2 +/- 0.7 to 8.8 +/- 1.1 mm, p = 0.0009, respectively), with a 15% increase in LV mass index (p = 0.0002). LV diameters, stroke volumes, and ejection fractions were unchanged. Mitral inflow showed a decrease in late-wave velocity (p = 0.00004), thus increasing the early (E)/A ratio. Septal and lateral Sm (p = 0.02) and Em velocities (p < 0.05) increased after training. In conclusion, the physiologic increase in LV mass in response to regular exercise in healthy young men occurs in parallel with a decrease in atrial contribution to flow. LV function estimated by tissue Doppler is improved despite the lack of changes in standard echocardiographic indexes. (c) 2006 Elsevier Inc. All rights reserved. C1 FMUSP, Inst Heart, INCOR, HC, Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Rodrigues, ACT (reprint author), FMUSP, Inst Heart, INCOR, HC, Sao Paulo, Brazil. EM claratude@yahoo.com RI Negrao, Carlos /C-4281-2012; OI Picard, Michael/0000-0002-9264-3243 NR 14 TC 21 Z9 22 U1 0 U2 2 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 APR 1 PY 2006 VL 97 IS 7 BP 1089 EP 1092 DI 10.1016/j.amjcard.2005.105.055 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 031MM UT WOS:000236708700033 PM 16563923 ER PT J AU Haddad, RI Posner, MR Busse, PM Norris, CM Goguen, LA Wirth, LJ Blinder, R Krane, JF Tishler, RB AF Haddad, RI Posner, MR Busse, PM Norris, CM Goguen, LA Wirth, LJ Blinder, R Krane, JF Tishler, RB TI Chemoradiotherapy for adenoid cystic carcinoma - Preliminary results of an organ sparing approach SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE adenoid cystic carcinoma; chemoradiotherapy; organ preservation; salivary gland neoplasm ID CISPLATIN-BASED CHEMOTHERAPY; SALIVARY-GLAND MALIGNANCIES; NECK-CANCER; PHASE-II; HEAD; RADIOTHERAPY; RADIATION; PACLITAXEL; NEOPLASMS; CYCLOPHOSPHAMIDE AB Objectives: A retrospective review of primary chemoradiotherapy (CRT) for adenoid cystic carcinoma (ACC) was performed to determine if CRT might be considered as an alternative to radiotherapy and/or definitive surgery. Methods: All treatment-naive patients with ACC of the head and neck who were treated with definitive primary chemoradiotherapy using carboplatinum and paclitaxel at Dana-Farber Cancer Institute in 2000 through 2004 were identified. Information on site, stage, presenting symptoms, performance status, treatment, toxicity, and follow up were collected and tabulated for review. Results: Five patients were identified with previously untreated ACC of the head and neck who received primary carboplatinum/paclitaxel CRT for unresectability or organ preservation. Patients had a median age of 41, 4 had primaries in the paranasal sinuses invading the base of skull and 1 had a transglottic laryngeal lesion. All patients completed a course of definitive chemoradiotherapy without treatment break. Grade 3 mucosal reactions developed during CRT in all patients. With a median follow-up of 36 months (range, 20-43) all patients have local regional control; 1 patient developed distant metastases at 7 months and is alive at 20 months. Conclusions: Preliminary data suggest that carboplatinum/paclitaxel based CRT for ACC provides local regional control and is a potential alternative to surgery or radiotherapy for patients with locally advanced ACC. Carboplatinum/paclitaxel based CRT wan-ants further study. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu NR 32 TC 32 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD APR PY 2006 VL 29 IS 2 BP 153 EP 157 DI 10.1097/01.coc.0000203756.36866.17 PG 5 WC Oncology SC Oncology GA 031PC UT WOS:000236715500010 PM 16601434 ER PT J AU Darabi, K Berg, AH AF Darabi, K Berg, AH TI Rituximab can be combined with daily plasma exchange to achieve effective B-cell depletion and clinical improvement in acute autoimmune TTP SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE thrombotic thrombocytopenic purpura; therapeutic apheresis; rituximab; autoimmune ID THROMBOTIC THROMBOCYTOPENIC PURPURA; DIAGNOSIS; REMISSION AB Much of idiopathic thrombotic thrombocytopenic purpura (TTP) is attributed to the presence of an autoantibody to ADAMTS-13, the metalloprotease that degrades ultralarge von Willebrand protein multimers. Most patients respond to treatment with therapeutic plasma exchange (TPE), which replaces the missing protease and removes the circulating inhibitor However, a substantial fraction of idiopathic TTP cases (10%-20%) might not respond to TPE alone, and, therefore, interest has been gathering around the use of the novel immunosuppressive anti-B-cell antibody, rituximab. We report 2 cases of refractory TTP in which the combined use of daily plasma exchange and rituximab was associated with clinical resolution of active TTP, and we discuss the benefits and possible timing of combined therapy. C1 Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst, Womens Hosp, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Darabi, K (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, GRJ-148,55 Fruit St, Boston, MA 02114 USA. EM kamrandarubi@yahoo.com NR 13 TC 35 Z9 37 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2006 VL 125 IS 4 BP 592 EP 597 DI 10.1309/RLNMJ01WBJRNLH03 PG 6 WC Pathology SC Pathology GA 024IS UT WOS:000236189300010 PM 16627268 ER PT J AU Merriman, NA Porter, SB Brensinger, CM Reddy, KR Chang, KM AF Merriman, NA Porter, SB Brensinger, CM Reddy, KR Chang, KM TI Racial difference in mortality among US veterans with HCV/HIV coinfection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSE; ALPHA-2A PLUS RIBAVIRIN; HIV-INFECTED PATIENTS; LIVER-DISEASE; ANTIRETROVIRAL THERAPY; NATURAL-HISTORY; PROTEASE INHIBITORS; DRUG-USERS AB OBJECTIVES: This study was performed to examine the impact of viral coinfections and race on clinical and virological outcome of hepatitis C virus (HCV) infection. METHODS: Three groups of patients (265 HCV/HIV coinfected, 251 HCV monoinfected, 227 HIV monoinfected) were identified between 2000 and 2002 from the computerized patient record system at the Philadelphia VA Medical Center and analyzed for clinical and virological parameters. RESULTS: HCV/HIV coinfection was associated with higher frequency of liver function abnormalities (37% vs 21% vs 20%; p < 0.0003) and greater mortality (17% vs 6% vs 9% over 3 yr period, p = 0.0003, p = 0.027) compared to HCV or HIV monoinfection, respectively. However, HCV/HIV coinfection was not associated with worsened HIV-related parameters (CD4 count, HIV titer, and use of antiretroviral therapy) or increased HCV titers compared to HIV or HCV monoinfection in our population, respectively. Interestingly, mortality among HCV/HIV coinfected patients was significantly greater in white than in black patients (31% vs 15%, p = 0.011). This racial disparity in mortality was not apparent in the monoinfected groups and not explained by HBV coinfection or history of alcohol use disorder. CONCLUSIONS: We conclude that HCV/HIV coinfection is associated with worsened liver disease and higher mortality than HCV- or HIV-monoinfection without directly influencing CD4 count and HCV or HIV titers. Furthermore, we demonstrated a racial disparity in survival of HCV/HIV-coinfected patients that needs further investigation. C1 Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Chang, KM (reprint author), Univ Penn, Sch Med, Dept Med, Div Gastroenterol, 600 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [M01-RR00040]; NIAAA NIH HHS [AA12849]; NIAID NIH HHS [AI47519]; NIDDK NIH HHS [P30DK50306] NR 41 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2006 VL 101 IS 4 BP 760 EP 767 DI 10.1111/j.1572-0241.2006.00531.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030WT UT WOS:000236666800016 PM 16494582 ER PT J AU McFarland, LV AF McFarland, LV TI Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; LACTOBACILLUS-RHAMNOSUS GG; SHORT GUT SYNDROME; SACCHAROMYCES-BOULARDII; DOUBLE-BLIND; HEALTH-CARE; NOSOCOMIAL DIARRHEA; RANDOMIZED-TRIAL; PUBLICATION BIAS; CLINICAL-TRIALS AB CONTEXT: Antibiotic-associated diarrhea (AAD) is a common complication of most antibiotics and Clostridium difficile disease (CDD), which also is incited by antibiotics, is a leading cause of nosocomial outbreaks of diarrhea and colitis. The use of probiotics for these two related diseases remains controversial. OBJECTIVE: To compare the efficacy of probiotics for the prevention of AAD and the treatment of CDD based on the published randomized, controlled clinical trials. DATA SOURCES: PubMed, Medline, Google Scholar, NIH registry of clinical trials, metaRegister, and Cochrane Central Register of Controlled Trials were searched from 1977 to 2005, unrestricted by language. Secondary searches of reference lists, authors, reviews, commentaries, associated diseases, books, and meeting abstracts. STUDY SELECTION: Trials were included in which specific probiotics given to either prevent or treat the diseases of interest. Trials were required to be randomized, controlled, blinded efficacy trials in humans published in peer-reviewed journals. Trials that were excluded were pre-clinical, safety, Phase I studies in volunteers, reviews, duplicate reports, trials of unspecified probiotics, trials of prebiotics, not the disease being studied, or inconsistent outcome measures. Thirty-one of 180 screened studies (totally 3,164 subjects) met the inclusion and exclusion criteria. DATA EXTRACTION: One reviewer identified studies and abstracted data on sample size, population characteristics, treatments, and outcomes. DATA SYNTHESIS: From 25 randomized controlled trials (RCTs), probiotics significantly reduced the relative risk of AAD (RR = 0.43, 95% CI 0.31, 0.58, p < 0.001). From six randomized trials, probiotics had significant efficacy for CDD (RR = 0.59, 95% CI 0.41, 0.85, p = 0.005). CONCLUSION: A variety of different types of probiotics show promise as effective therapies for these two diseases. Using meta-analyses, three types of probiotics (Saccharomyces boulardii, Lactobacillus rhamnosus GG, and probiotic mixtures) significantly reduced the development of antibiotic-associated diarrhea. Only S. boulardii was effective for CDD. C1 VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. RP VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, S-152,Metropolitan Pk W,1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. NR 78 TC 357 Z9 399 U1 14 U2 77 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2006 VL 101 IS 4 BP 812 EP 822 DI 10.1111/j.1572-0241.2006.00465.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030WT UT WOS:000236666800024 PM 16635227 ER PT J AU Pe'er, I Chretien, YR de Bakker, PIW Barrett, JC Daly, MJ Altshuler, DM AF Pe'er, I Chretien, YR de Bakker, PIW Barrett, JC Daly, MJ Altshuler, DM TI Biases and reconciliation in estimates of linkage disequilibrium in the human genome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COMMON DISEASE GENES; HAPLOTYPE DIVERSITY; SEQUENCE VARIATION; HUMAN-POPULATIONS; WIDE ASSOCIATION; RECOMBINATION; PATTERNS; BLOCKS; TRAITS AB Genetic association studies of common disease often rely on linkage disequilibrium ( LD) along the human genome and in the population under study. Although understanding the characteristics of this correlation has been the focus of many large-scale surveys ( culminating in genomewide haplotype maps), the results of different studies have yielded wide-ranging estimates. Since understanding these differences ( and whether they can be reconciled) has important implications for whole-genome association studies, in this article we dissect biases in these estimations that are due to known aspects of study design and analytic methodology. In particular, we document in the empirical data that the long-known complicating effects of allele frequency, marker density, and sample size largely reconcile all large-scale surveys. Two exceptions are an underappraisal of redundancy among single-nucleotide polymorphisms ( SNPs) when evaluation is limited to short regions ( as in candidate-gene resequencing studies) and an inflation in the extent of LD in HapMap phase I, which is likely due to oversampling of specific haplotypes in the creation of the public SNP map. Understanding these factors can guide the understanding of empirical LD surveys and has implications for genetic association studies. C1 Massachusetts Gen Hosp, Richard B Simches Res Ctr, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Richard B Simches Res Ctr, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu RI 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 43 TC 30 Z9 32 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2006 VL 78 IS 4 BP 588 EP 603 DI 10.1086/502803 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 032EE UT WOS:000236755900006 PM 16532390 ER PT J AU Wolf, M Holmes, J Isakova, T AF Wolf, M Holmes, J Isakova, T TI Post-transplant hypophosphatemia: Tertiary "hyper-phosphatoninism"? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 19-23, 2006 CL Chicago, IL SP Natl Kidney Fdn C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2006 VL 47 IS 4 MA 174 BP A62 EP A62 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 032EK UT WOS:000236756500196 ER PT J AU Gonzalez, RG AF Gonzalez, RG TI Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology is brain" SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID TISSUE-PLASMINOGEN ACTIVATOR; DIFFUSION-WEIGHTED MR; CEREBRAL-ARTERY STROKE; INTRAARTERIAL THROMBOLYSIS; HYPERACUTE STROKE; BLOOD-FLOW; INTRACEREBRAL HEMORRHAGE; CLINICAL-EXPERIENCE; CT ANGIOGRAPHY; INTRAVENOUS THROMBOLYSIS AB The number of potential patients who are actually treated for acute ischemic stroke is disappointingly low, and effective treatments are making a minor impact on this major public health problem. Imaging is not regularly used to identify the ischemic penumbra, a key concept in stroke physiology, though it is capable of doing so in a clinically relevant manner. Evidence is accumulating that identification of the ischemic penumbra and making treatment decisions on the basis of its presence provide substantial benefit to patient outcomes. Moreover, the same studies suggest that an unexpectedly large proportion of patients are suitable for therapy well past the traditional time windows because of the existence of a substantial ischemic penumbra. Modern MR imaging and CT systems, now widely available, are capable of answering the most relevant physiologic questions in acute ischemic stroke. This capability presents new opportunities and responsibilities to neuroradiologists to make appropriate imaging readily available and to have the imaging data rapidly processed and interpreted. In this article, acute ischemic stroke therapy, including the role of imaging in current medical practice, is reviewed, and an evidence-based alternative to contemporary acute ischemic stroke therapy is suggested. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, Boston, MA 02214 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02214 USA. FU NINDS NIH HHS [NS50041] NR 86 TC 64 Z9 78 U1 1 U2 5 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 APR PY 2006 VL 27 IS 4 BP 728 EP 735 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033BY UT WOS:000236822500006 PM 16611754 ER PT J AU Boxerman, JL Schmainda, KM Weisskoff, RM AF Boxerman, JL Schmainda, KM Weisskoff, RM TI Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Neuroradiology CY JUN 05-11, 2004 CL Seattle, WA SP Amer Soc Neuroradiol ID INTRACRANIAL MASS LESIONS; HUMAN BRAIN-TUMORS; GRADIENT-ECHO; ENHANCED MRI; TRANSIT-TIME; PERFUSION; ANGIOGENESIS; ASTROCYTOMAS; NEOPLASMS; DTPA AB BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) estimates for high-grade gliomas computed with dynamic susceptibility contrast MR imaging are artificially lowered by contrast extravasation through a disrupted blood-brain barrier. We hypothesized that rCBV corrected for agent leakage would correlate significantly with histopathologic tumor grade, whereas uncorrected rCBV would not. METHODS: We performed dynamic T2*-weighted perfusion MR imaging on 43 patients with a cerebral glioma after prebolus gadolinium diethylene triamine penta-acetic acid administration to diminish competing extravasation-induced T1 effects. The rCBV was computed from non-necrotic enhancing tumor regions by integrating the relaxivity-time data, with and without contrast extravasation correction by using a linear fitting algorithm, and was normalized to contralateral brain. We determined the statistical correlation between corrected and uncorrected normalized rCBV and histopathologic tumor grade with the Spearman rank correlation test. RESULTS: Eleven, 9, and 23 patients had WHO grades II, III, and IV glioma, respectively. Mean uncorrected normalized rCBVs were 1.53, 2.51, and 2.14 (grade II, III, and IV). Corrected normalized rCBVs were 1.52, 2.84, and 3.96. Mean absolute discrepancies between uncorrected and corrected rCBVs were 2% (0%-15%), 16% (0%-106%), and 74% (0%-411%). The correlation between corrected rCBV and tumor grade was significant (0.60; P < .0001), whereas it was not for uncorrected rCBV (0.15; P = .35). CONCLUSION: For gliomas, rCBV estimation that correlates significantly with WHO tumor grade necessitates contrast extravasation correction. Without correction, artificially lowered rCBV may be construed erroneously to reflect lower tumor grade. C1 Brown Univ, Sch Med, Rhode Isl Hosp, Dept Radiol, Providence, RI 02903 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Boxerman, JL (reprint author), Brown Univ, Sch Med, Rhode Isl Hosp, Dept Radiol, 593 Eddy St, Providence, RI 02903 USA. FU NCI NIH HHS [R01-CA082500]; NCRR NIH HHS [M01-RR00058]; NHLBI NIH HHS [R01-HL39810] NR 49 TC 279 Z9 285 U1 1 U2 15 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 APR PY 2006 VL 27 IS 4 BP 859 EP 867 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033BY UT WOS:000236822500031 PM 16611779 ER PT J AU Gorniak, RJT Young, GS Wiese, DE Marty, FM Schwartz, RB AF Gorniak, RJT Young, GS Wiese, DE Marty, FM Schwartz, RB TI MR imaging of human herpesvirus-6-associated encephalitis in 4 patients with anterograde amnesia after allogeneic hematopoietic stem-cell transplantation SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; HUMAN-HERPESVIRUS 6; PARANEOPLASTIC LIMBIC ENCEPHALITIS; IMMUNOCOMPETENT ADULT; VIRUS-6 ENCEPHALITIS; MENINGOENCEPHALITIS; INFECTION; ENCEPHALOMYELITIS; RECIPIENT AB MR imaging is typically obtained during the work-up of patients who have undergone allogeneic hematopoietic stem-cell transplant who present with unexplained change in mental status, amnesia, or seizures. Although the differential diagnosis is broad in this setting, the presence of T2 prolongation limited to the medial aspect of one or both temporal lobes with or without associated reduced water diffusion may help limit the possible diagnoses. A frequent etiology seen in this context is human herpesvirus-6 (HHV6) infection. We report the evolution of MR imaging findings and clinical course in 4 patients with limbic encephalitis probably related to HHV6. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Neuroradiol Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Longwood MRI Specialists, Brookline, MA USA. RP Gorniak, RJT (reprint author), Thomas Jefferson Univ Hosp, 132 S 10th St,Suite 1070, Philadelphia, PA 19107 USA. NR 28 TC 38 Z9 40 U1 1 U2 3 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 APR PY 2006 VL 27 IS 4 BP 887 EP 891 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 033BY UT WOS:000236822500037 PM 16611785 ER PT J AU Choi, JY Sandberg, MA Berson, EL AF Choi, JY Sandberg, MA Berson, EL TI Natural course of ocular function in pigmented paravenous retinochoroidal atrophy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To estimate mean rates of change of ocular function in patients with pigmented paravenous retinochoroidal atrophy (PPRCA). DESIGN: Retrospective observational case series. METHODS: Fifteen patients aged 8 to 67 years with PPRCA were followed for 3 to 35 years (average follow-up time, 13 years) with measures of visual acuity, visual field area, and full,field electroretinogram amplitude. Mean annual exponential rates of change were quantified by repeated measures longitudinal regression. RESULTS: Estimated mean annual rates of change were -2.0% for Visual acuity, +0.3% for visual field area, and -3.4% and -6.7% for 0.5 Hz and 30 Hz electroretinogram amplitudes, respectively. CONCLUSION: Patients with PPRCA have a slowly progressive disease with respect to the loss of peripheral vision. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab, 243 Charles St, Boston, MA 02114 USA. EM Linda_Berard@meei.harvard.edu FU NEI NIH HHS [EY00169] NR 6 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2006 VL 141 IS 4 BP 763 EP 765 DI 10.1016/j.ajo.2005.11.009 PG 3 WC Ophthalmology SC Ophthalmology GA 030GG UT WOS:000236621800033 PM 16564825 ER PT J AU Maguen, S Armistead, L AF Maguen, S Armistead, L TI Abstinence among female adolescents: Do parents matter above and beyond the influence of peers? SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE adolescent; sexual behavior; parents ID SEXUAL-BEHAVIOR; RISK BEHAVIORS; YOUTH; FAMILY; PROGRAMS AB The purpose of this study was to determine whether parental variables predict abstinence above and beyond the influence of peer variables in a sample of African American adolescent females (n = 568). In order to determine predictors of abstinence, hierarchical logistic regressions were conducted for the entire sample, the younger adolescent girls, and the older adolescent girls. Results indicated that for the total sample and older adolescents, both parental sexual attitudes and parent-adolescent relationship quality predicted abstinence after accounting for the variance associated with peer variables. For the younger girls, perceived parental attitudes were the only significant predictor. These findings suggest that adolescent sexual risk reduction interventions may benefit from including parents, stressing the importance of articulating parental sexual attitudes, and highlighting the significance of the parent-adolescent relationship. C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Armistead, L (reprint author), Georgia State Univ, Dept Psychol, POB 5010, Atlanta, GA 30303 USA. EM psylxa@langate.gsu.edu NR 20 TC 23 Z9 23 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD APR PY 2006 VL 76 IS 2 BP 260 EP 264 DI 10.1037/0002-9432.76.2.260 PG 5 WC Psychiatry; Social Work SC Psychiatry; Social Work GA 046LR UT WOS:000237813600014 PM 16719645 ER PT J AU Lisi, S Botta, R Pinchera, A Collins, AB Refetoff, S Arvan, P Bu, GJ Grasso, L Marshansky, V Bechoua, S Hurtado-Lorenzo, A Marcocci, C Brown, D McCluskey, RT Marino, M AF Lisi, S Botta, R Pinchera, A Collins, AB Refetoff, S Arvan, P Bu, GJ Grasso, L Marshansky, V Bechoua, S Hurtado-Lorenzo, A Marcocci, C Brown, D McCluskey, RT Marino, M TI Defective thyroglobulin storage in LDL receptor-associated protein-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE low-density lipoprotein; knockout mice ID THYROID-HORMONE RELEASE; SPECIALIZED CHAPERONE; ENDOCYTIC RECEPTORS; RAP; MEGALIN; GP330; CELLS; HYPOTHYROIDISM; IDENTIFICATION; TRANSCYTOSIS AB The molecular chaperone receptor-associated protein (RAP) is required for biosynthesis of megalin, an endocytic receptor for follicular thyroglobulin (Tg), the thyroid hormone precursor. RAP also binds to Tg itself, suggesting that it may affect Tg trafficking in various manners. To elucidate RAP function, we have studied the thyroid phenotype in RAP-knockout (RAP-KO) mice and found a reduction of Tg aggregates into thyroid follicles. Serum Tg levels were significantly increased compared with those of wild-type (WT) mice, suggesting a directional alteration of Tg secretion. In spite of these abnormalities, hormone secretion was maintained as indicated by normal serum thyroxine levels. Because Tg in thyroid extracts from RAP-KO mice contained thyroxine residues as in WT mice, we concluded that in RAP-KO mice, follicular Tg, although reduced, was nevertheless sufficient to provide normal hormone secretion. Serum TSH was increased in RAP-KO mice, and although no thyroid enlargement was observed, some histological features resembling early goiter were present. Megalin was decreased in RAP-KO mice, but this did not affect thyroid function, probably because of the concomitant reduction of follicular Tg. In conclusion, RAP is required for the establishment of Tg reservoirs, but its absence does not affect hormone secretion. C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Michigan, Div Endocrinol Diabet & Metab, Ann Arbor, MI 48109 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Physiol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit,Program Membrane Biol, Charlestown, MA USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. EM m.marino@endoc.med.unipi.it RI Hurtado-Lorenzo, Ph.D., Andres/A-8331-2009 FU NIDDK NIH HHS [DK-38456, DK-15070] NR 26 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2006 VL 290 IS 4 BP C1160 EP C1167 DI 10.1152/ajpcell.00382.2005. PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 029OP UT WOS:000236573300025 PM 16306127 ER PT J AU Malo, MS Mozumder, M Zhang, XB Biswas, S Chen, A Bai, LC Merchant, JL Hodin, RA AF Malo, MS Mozumder, M Zhang, XB Biswas, S Chen, A Bai, LC Merchant, JL Hodin, RA TI Intestinal alkaline phosphatase gene expression is activated by ZBP-89 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE carcinogenesis; development; enterocyte differentiation; eukaryotic promoter; transient transfection ID TRANSCRIPTION FACTOR ZBP-89; SURFACTANT-LIKE PARTICLES; ZINC-FINGER PROTEIN; KRUPPEL-LIKE FACTOR; CHAIN FATTY-ACIDS; ENTEROCYTE DIFFERENTIATION; THYROID-HORMONE; GROWTH-STATE; PROMOTER; CELLS AB Intestinal alkaline phosphatase gene expression is activated by ZBP-89. Am J Physiol Gastrointest Liver Physiol 290: G737-G746, 2006. First published December 29, 2005; doi:10.1152/ajpgi.00394.2005.-Intestinal alkaline phosphatase (IAP) is an enterocyte differentiation marker that functions to limit fat absorption. Zinc finger binding protein-89 (ZBP-89) is a Kruppel-type transcription factor that appears to promote a differentiated phenotype in the intestinal epithelium. The purpose of this study was to investigate the regulation of IAP gene expression by ZBP-89. RT-PCR, quantitative real-time RT-PCR, Western blot analyses, and reporter assays were used to determine the regulation of IAP by ZBP-89 in HT-29 and Caco-2 colon cancer cells. ZBP-89 knockdown was achieved by specific short interfering ( si) RNA. EMSA and chromatin immunoprecipitation (ChIP) were performed to examine the binding of ZBP-89 to the IAP promoter. The results of RT-PCR, quantitative real-time PCR, and Western blot analyses showed that ZBP-89 was expressed at low levels in Caco-2 and HT-29 cells, whereas IAP was minimally expressed and absent in these cells, respectively. Transfection with ZBP-89 expression plamid increased IAP mRNA and protein levels in both cell lines, whereas knockdown of endogenous ZBP-89 by siRNA reduced basal levels of IAP gene expression in Caco-2 cells. IAP-luciferase reporter assays, EMSA, and ChIP established that ZBP-89 activated the IAP gene through a response element (ZBP-89 response element: 5'-CCTCCTCCC-3') located between -1018 and -1010 bp upstream of the AUG start codon. We conclude that ZBP-89 is a direct transcriptional activator of the enterocyte differentiation marker IAP. These findings are consistent with the role that this transcription factor is thought to play as a tumor suppressor and suggests its possible function in the physiology of fat absorption. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, Gray 504,55 Fruit St, Boston, MA 02114 USA. EM rhodin@partners.org FU NIDDK NIH HHS [R01-DK-47186, R01-DK-55732]; PHS HHS [R01-55732] NR 42 TC 17 Z9 17 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 APR PY 2006 VL 290 IS 4 BP G737 EP G746 DI 10.1152/ajpgi.00394.2005 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 021OJ UT WOS:000235992200020 PM 16384873 ER PT J AU Rumbaut, RE Bellera, RV Randhawa, JK Shrimpton, CN Dasgupta, SK Dong, JF Burns, AR AF Rumbaut, RE Bellera, RV Randhawa, JK Shrimpton, CN Dasgupta, SK Dong, JF Burns, AR TI Endotoxin enhances microvascular thrombosis in mouse cremaster venules via a TLR4-dependent, neutrophil-independent mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE microcirculation; platelets; endothelium; endotoxemia ID TOLL-LIKE RECEPTOR-4; ENDOTHELIAL CELL-ADHESION; VON-WILLEBRAND-FACTOR; IN-VIVO; BACTERIAL LIPOPOLYSACCHARIDE; PLATELET-AGGREGATION; VONWILLEBRAND-FACTOR; INTESTINAL VENULES; P-SELECTIN; IFN-GAMMA AB Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo. We sought to determine whether endotoxin (lipopolysaccharide, LPS) modified platelet thrombus formation in mouse cremaster venules and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with Escherichia coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by similar to 50% (P < 0.005) compared with saline-treated animals. Enhanced microvascular thrombosis was evident as early as 2 h after LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo and did not influence platelet P-selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils and without enhancement of platelet aggregation, via a TLR4-dependent mechanism. C1 Baylor Coll Med, Childrens Nutr Res Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, Childrens Nutr Res Ctr, Dept Med, 1100 Bates,Rm 6014, Houston, TX 77030 USA. EM rrumbaut@bcm.tmc.edu FU NHLBI NIH HHS [HL-64721, HL-070537, HL-42550, R01 HL079368, R01 HL079368-01A1]; NIAID NIH HHS [AI-46773] NR 47 TC 48 Z9 48 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2006 VL 290 IS 4 BP H1671 EP H1679 DI 10.1152/ajpheart.00305.2005 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 021GU UT WOS:000235972500044 PM 16284241 ER PT J AU Sohn, M Tan, Y Wang, B Klein, RL Trojanowska, M Jaffa, AA AF Sohn, M Tan, Y Wang, B Klein, RL Trojanowska, M Jaffa, AA TI Mechanisms of low-density lipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE transforming growth factor-beta; mitogen-activated protein kinase; collagen IV ID SMOOTH-MUSCLE-CELLS; ANGIOGENESIS IN-VIVO; MESANGIAL CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; ATHEROSCLEROTIC LESIONS; SIGNAL-TRANSDUCTION; ARTERIAL INJURY; GENE-REGULATION; FACTOR-BETA; TGF-BETA AB Hyperlipidemia is a recognized risk factor for atherosclerotic vascular disease. The underlying mechanisms that link lipoproteins and vascular disease are undefined. Connective tissue growth factor (CTGF) is emerging as a key determinant of progressive fibrotic diseases, and its expression is upregulated by diabetes. To define the mechanisms through which low-density lipoproteins (LDL) promote vascular injury, we evaluated whether LDL can modulate the expression of CTGF and collagen IV in human aortic endothelial cells (HAECs). Treatment of HAECs with LDL (50 mu g/ml) for 24 h produced a significant increase in the mRNA and the protein levels of CTGF and collagen IV compared with unstimulated controls. To explore the mechanisms by which LDL regulates CTGF and collagen IV expression in HAECs, we determined first if CTGF and collagen IV are downstream targets for regulation by transforming growth factor-beta (TGF-beta). The results demonstrated that TGF-beta produced a concentration-dependent increase in the protein levels of CTGF. To assess whether the induction of CTGF in response to LDL is mediated via autocrine activation of TGF-beta, HAECs were treated with LDL for 24 h in the presence and absence of anti-TGF-beta neutralizing antibodies (anti-TGF- beta NA). The results demonstrated that the increase in CTGF induced by LDL was significantly inhibited by the anti-TGF-beta NA. To investigate the upstream mediators of TGF-beta on activity of CTGF in response to LDL, HAECs were treated with LDL for 24 h in the presence and absence of cell-permeable MAPK inhibitors. Inhibition of p38(mapk) activities did not affect LDL-induced TGF-beta 1, CTGF, and collagen IV expression. On the other hand, SP-600125, a specific inhibitor of c-Jun NH2-terminal kinase, suppressed LDL-induced TGF-beta, CTGF, and collagen IV expression, and PD-98059, a selective inhibitor of p44/42(mapk), suppressed LDL-induced TGF-beta and CTGF expression. These findings are the first to implicate the MAPK pathway and TGF-beta as key players in LDL signaling, leading to CTGF and collagen IV expression in HAECs. The data also point to a potential mechanistic pathway through which lipoproteins may promote vascular injury. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet Med Genet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 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 OI Trojanowska, Maria/0000-0001-9550-7178 FU NHLBI NIH HHS [HL-55782]; NIDDK NIH HHS [DK-46543] NR 43 TC 18 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2006 VL 290 IS 4 BP H1624 EP H1634 DI 10.1152/ajpheart.01233.2004 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 021GU UT WOS:000235972500039 PM 16272194 ER PT J AU Busch, CJ Liu, HL Graveline, AR Bloch, KD AF Busch, CJ Liu, HL Graveline, AR Bloch, KD TI Nitric oxide induces phosphodiesterase 4B expression in rat pulmonary artery smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE cross talk; S-nitroso-L-glutathione; adenosine 3 ',5 '-cyclic monophosphate; guanosine 3 ',5 '-cyclic monophosphate ID DEPENDENT PROTEIN-KINASE; CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; FACTOR CREB; CGMP; GMP; PHOSPHORYLATION; PDE4; INHIBITION; PATHWAY; AMP AB Phosphodiesterases (PDE) metabolize cyclic nucleotides limiting the effects of vasodilators such as prostacyclin and nitric oxide ( NO). In this study, DNA microarray techniques were used to assess the impact of NO on expression of PDE genes in rat pulmonary arterial smooth muscle cells (rPASMC). Incubation of rPASMC with S-nitroso-L-glutathione (GSNO) increased expression of a PDE isoform that specifically metabolizes cAMP (PDE4B) in a dose- and time-dependent manner. GSNO increased PDE4B protein levels, and rolipram-inhibitable PDE activity was 2.3 +/- 1.0-fold greater in GSNO-treated rPASMC than in untreated cells. The soluble guanylate cyclase (sGC) inhibitor, 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one, and the cAMP-dependent protein kinase inhibitor, H89, prevented induction of PDE4B gene expression by GSNO, but the protein kinase G (PKG) inhibitors, Rp-8-pCPT-cGMPs and KT-5823, did not. Incubation of rPASMC with IL-1 beta and tumor necrosis factor-alpha induced PDE4B gene expression, an effect that was inhibited by L-N-6-(1-iminoethyl)lysine, an antagonist of NO synthase 2 (NOS2). The GSNO-induced increase in PDE4B mRNA levels was blocked by actinomycin D but augmented by cycloheximide. Infection of rPASMC with an adenovirus specifying a dominant negative cAMP response element binding protein ( CREB) mutant inhibited the GSNO-induced increase of PDE4B gene expression. These results suggest that exposure of rPASMC to NO induces expression of PDE4B via a mechanism that requires cGMP synthesis by sGC but not PKG. The GSNO-induced increase of PDE4B gene expression is CREB dependent. These findings demonstrate that NO increases expression of a cAMP-specific PDE and provide evidence for a novel "cross talk" mechanism between cGMP and cAMP signaling pathways. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA USA. RP Heidelberg Univ, Dept Anesthesiol, Neuenheimer Feld 110, D-69120 Heidelberg, Germany. EM Cornelius_Busch@med.uni-heidelberg.de FU NHLBI NIH HHS [HL-74352] NR 41 TC 8 Z9 10 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2006 VL 290 IS 4 BP L747 EP L753 DI 10.1152/ajplung.00298.2005 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 029ON UT WOS:000236573100014 PM 16299053 ER PT J AU Evgenov, OV Busch, CJ Evgenov, NV Liu, R Petersen, B Falkowski, GE Petho, B Vas, A Bloch, KD Zapol, WM Ichinose, F AF Evgenov, OV Busch, CJ Evgenov, NV Liu, R Petersen, B Falkowski, GE Petho, B Vas, A Bloch, KD Zapol, WM Ichinose, F TI Inhibition of phosphodiesterase 1 augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs with acute pulmonary hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE guanosine 3 ',5 '-cyclic monophosphate; vinpocetine; sheep ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; ARTERIAL-HYPERTENSION; CAPILLARY-PRESSURE; ORAL SILDENAFIL; SMOOTH-MUSCLE; LUNG; CALMODULIN; IDENTIFICATION; VINPOCETINE; EXPRESSION AB Phosphodiesterase 1 (PDE1) modulates vascular tone and the development of tolerance to nitric oxide (NO)-releasing drugs in the systemic circulation. Any role of PDE1 in the pulmonary circulation remains largely uncertain. We measured the expression of genes encoding PDE1 isozymes in the pulmonary vasculature and examined whether or not selective inhibition of PDE1 by vinpocetine attenuates pulmonary hypertension and augments the pulmonary vasodilator response to inhaled NO in lambs. Using RT-PCR, we detected PDE1A, PDE1B, and PDE1C mRNAs in pulmonary arteries and veins isolated from healthy lambs. In 13 lambs, the thromboxane A(2) analog U-46619 was infused intravenously to increase mean pulmonary arterial pressure to 35 mmHg. Four animals received an intravenous infusion of vinpocetine at incremental doses of 0.3, 1, and 3 mg center dot kg(-1)center dot h(-1). In nine lambs, inhaled NO was administered in a random order at 2, 5, 10, and 20 ppm before and after an intravenous infusion of 1 mg center dot kg(-1)center dot h(-1) vinpocetine. Administration of vinpocetine did not alter pulmonary and systemic hemodynamics or transpulmonary cGMP or cAMP release. Inhaled NO selectively reduced mean pulmonary arterial pressure, pulmonary capillary pressure, and pulmonary vascular resistance index, while increasing transpulmonary cGMP release. The addition of vinpocetine enhanced pulmonary vasodilation and transpulmonary cGMP release induced by NO breathing without causing systemic vasodilation but did not prolong the duration of pulmonary vasodilation after NO inhalation was discontinued. Our findings demonstrate that selective inhibition of PDE1 augments the therapeutic efficacy of inhaled NO in an ovine model of acute chemically induced pulmonary hypertension. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Gedeon Richter Chem Works Ltd, Budapest, Hungary. RP Evgenov, OV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,CLN 309, Boston, MA 02114 USA. EM evgenov@etherdome.mgh.harvard.edu FU NHLBI NIH HHS [HL-42397, HL-71987, HL-74352] NR 40 TC 18 Z9 18 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2006 VL 290 IS 4 BP L723 EP L729 DI 10.1152/ajplung.00485.2004 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 029ON UT WOS:000236573100011 PM 16284211 ER PT J AU Fan, J Li, YH Vodovotz, Y Billiar, TR Wilson, MA AF Fan, J Li, YH Vodovotz, Y Billiar, TR Wilson, MA TI Hemorrhagic shock-activated neutrophils augment TLR4 signaling-induced TLR2 upregulation in alveolar macrophages: role in hemorrhage-primed lung inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE acute lung injury; lipopolysaccharide; innate immunity; peptidoglycan; Toll-like receptor ID TOLL-LIKE RECEPTOR-2; NF-KAPPA-B; MULTIPLE ORGAN FAILURE; TUMOR-NECROSIS-FACTOR; CUTTING EDGE; ENDOTHELIAL-CELLS; DIFFERENTIAL EXPRESSION; SELECTIVE EXPRESSION; CELLULAR ACTIVATION; DENDRITIC CELLS AB Hemorrhagic shock renders patients susceptible to the development of acute lung injury in response to a second inflammatory stimulus by as yet unclear mechanisms. We investigated the role of neutrophils (PMN) in alveolar macrophage (AM phi) priming, specifically, the role in mediating Toll-like receptor (TLR)4 and TLR2 cross talk in AM phi. Using a mouse model of hemorrhagic shock followed by intratracheal administration of LPS, we explored a novel function of shock-activated PMN in the mechanism of TLR2 upregulation induced by LPS-TLR4 signaling in AM phi. We showed that antecedent hemorrhagic shock enhanced LPS-induced TLR2 upregulation in AM phi. In neutropenic mice subjected to shock, the LPS-induced TLR2 expression was significantly reduced, and the response was restored upon repletion with PMN obtained from shock-resuscitated mice but not by PMN from sham-operated mice. These findings were recapitulated in mouse AM phi cocultured with PMN. The enhanced TLR2 upregulation in AM phi augmented the expression of macrophage inflammatory protein-2, TNF-alpha, and macrophage migration inhibitory factor in the AM phi in response to sequential challenges of LPS and peptidoglycan, a prototypical TLR2 ligand, which physiologically associated with amplified AM phi-induced PMN migration into air pouch and lung alveoli. Thus TLR2 expression in AM phi, signaled by TLR4 and regulated by shock-activated PMN, is an important positive-feedback mechanism responsible for shock-primed PMN infiltration into the lung after primary PMN sequestration. C1 VA Pittsburgh Healthcare Syst, Dept Surg, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15240 USA. RP Fan, J (reprint author), VA Pittsburgh Healthcare Syst, Dept Surg, CHERP Bldg 28,Univ Dr C, Pittsburgh, PA 15240 USA. EM jif7@pitt.edu FU NHLBI NIH HHS [HL-079669] NR 39 TC 53 Z9 55 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2006 VL 290 IS 4 BP L738 EP L746 DI 10.1152/ajplung.00280.2005 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 029ON UT WOS:000236573100013 PM 16272176 ER PT J AU Hurley, BP Williams, NL McCormick, BA AF Hurley, BP Williams, NL McCormick, BA TI Involvement of phospholipase A(2) in Pseudomonas aeruginosa-mediated PMN transepithelial migration SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung inflammation; arachidonic acid; eicosanoid; polymorphonuclear cells; neutrophils ID BRONCHIAL EPITHELIAL-CELLS; ARACHIDONIC-ACID RELEASE; LUNG; GENE; INTERLEUKIN-8; NEUTROPHILS; ACTIVATION; EXPRESSION; INDUCTION; ALPHA AB Inflammation resulting from bacterial infection of the respiratory mucosal surface during pneumonia and cystic fibrosis contributes to pathology. A major consequence of the inflammatory response is recruitment of polymorphonuclear cells (PMNs) to the infected site. To reach the airway, PMNs must travel through several cellular and extracellular barriers, via the actions of multiple cytokines, chemokines, and adhesion molecules. Using a model of polarized lung epithelial cells (A549 or Calu-3) grown on Transwell filters and human PMNs, we have shown that Pseudomonas aeruginosa induces PMN migration across lung epithelial barriers. The process is mediated by epithelial production of the eicosanoid hepoxilin A(3) (HXA(3)) in response to P. aeruginosa infection. HXA(3) is a PMN chemoattractant metabolized from arachidonic acid (AA). Given that release of AA is believed to be the rate-limiting step in generating eicosanoids, we investigated whether P. aeruginosa infection of lung epithelial cells resulted in an increase in free AA. P. aeruginosa infection of A549 or Calu-3 monolayers resulted in a significant increase in [H-3]AA released from prelabeled lung epithelial cells. This was partially inhibited by PLA(2) inhibitors ONO-RS-082 and ACA as well as an inhibitor of diacylglycerol lipase. Both PLA(2) inhibitors dramatically reduced P. aeruginosa-induced PMN transmigration, whereas the diacylglycerol lipase inhibitor had no effect. In addition, we observed that P. aeruginosa infection caused an increase in the phosphorylation of cytosolic PLA(2) ( cPLA(2)), suggesting a mechanism whereby P. aeruginosa activates cPLA(2) generating free AA that may be converted to HXA(3), which is required for mediating PMN transmigration. C1 Massachusetts Gen Hosp, Mucosal Immunol Labs, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Hurley, BP (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Labs, Charlestown, MA 02129 USA. EM Bphurley@partners.org FU NIDDK NIH HHS [DK-56754, P30 DK040561-11, P30 DK040561] NR 32 TC 13 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2006 VL 290 IS 4 BP L703 EP L709 DI 10.1152/ajplung.00390.2005 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 029ON UT WOS:000236573100009 PM 16272174 ER PT J AU Friedman, MJ AF Friedman, MJ TI Posttraumatic stress disorder among military returnees from Afghanistan and Iraq SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MENTAL-HEALTH; WAR; INFORMATION; EXPOSURE; TRAUMA; CARE C1 Dartmouth Coll, Sch Med, Dept Psychiat, Hanover, NH USA. Dartmouth Coll, Sch Med, Dept Pharmacol & Toxicol, Hanover, NH USA. Natl Ctr PTSD, US Dept Vet Affairs, Hanover, NH USA. RP Friedman, MJ (reprint author), VA Med Ctr, Natl Ctr PTSD, 215 N Main St, White River Jct, VT 05009 USA. EM matthew.j.friedman@dartmouth.edu NR 37 TC 70 Z9 72 U1 4 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 586 EP 593 DI 10.1176/appi.ajp.163.4.586 PG 8 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200008 PM 16585431 ER PT J AU Woodward, SH Kaloupek, DG Streeter, CC Kimble, MO Reiss, AL Eliez, S Wald, LL Renshaw, PF Frederick, BB Lane, B Sheikh, JI Stegman, WK Kutter, CJ Stewart, LP Prestel, RS Arsenault, NJ AF Woodward, SH Kaloupek, DG Streeter, CC Kimble, MO Reiss, AL Eliez, S Wald, LL Renshaw, PF Frederick, BB Lane, B Sheikh, JI Stegman, WK Kutter, CJ Stewart, LP Prestel, RS Arsenault, NJ TI Hippocampal volume, PTSD, and alcoholism in combat veterans SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; WHITE-MATTER VOLUME; QUANTITATIVE-ANALYSIS; BRAIN-DEVELOPMENT; MRI; VALIDITY; DEFICITS; RELIABILITY; WOMEN AB Studies imposing rigorous control over lifetime alcohol intake have usually not found smaller hippocampal volumes in persons with posttraumatic stress disorder. Because the majority of negative studies have used adolescent samples, it has been suggested that chronicity is a necessary condition for such findings. To test the hypothesis that a smaller hippocampus in PTSD is unrelated to comorbid alcoholism or to chronicity, this study estimated hippocampal volume in a relatively large group ( N=99) of combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. In subjects with histories of alcoholism, unadjusted hippocampal volume was 9% smaller in persons with PTSD than in those without PTSD. In nonalcoholic subjects, the PTSD-related difference in hippocampal volume was 3%. The failure to observe a strong association between PTSD and hippocampal volume in nonalcoholic subjects was not ascribable to younger age, reduced PTSD chronicity, or lower PTSD symptom severity. The possibility that smaller hippocampal volume is limited to groups in which PTSD is compounded by comorbid alcoholism is not necessarily incompatible with results suggesting a smaller hippocampus is predispositional to PTSD. Further examination of the role of alcoholism and other comorbid conditions in studies of brain structure and function in PTSD appears warranted. C1 Natl Ctr PTSD, Clin Lab & Educ Div, Va Palo Alto HCS, Palo Alto, CA 94304 USA. Natl Ctr PTSD, VA Palo Alto Healthcare Syst, Psychol Serv, Palo Alto, CA 94304 USA. VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. Middlebury Coll, Dept Psychol, Middlebury, VT 05753 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA. Univ Geneva, Dept Psychiat, Geneva, Switzerland. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA USA. White River Junct Vet Affairs Med Ctr, Psychol Serv, White River Jct, VT USA. Univ Oregon, Dept Psychol, Eugene, OR 97403 USA. RP Woodward, SH (reprint author), Natl Ctr PTSD, Clin Lab & Educ Div, Va Palo Alto HCS, Mail Code 334 PTSD,3801 Miranda Ave, Palo Alto, CA 94304 USA. EM steve.woodward@med.va.gov RI Frederick, Blaise/G-6098-2012; Wald, Lawrence/D-4151-2009 OI Frederick, Blaise/0000-0001-5832-5279; FU NIAAA NIH HHS [K23AA131149] NR 59 TC 43 Z9 44 U1 3 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 674 EP 681 DI 10.1176/appi.ajp.163.4.674 PG 8 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200020 PM 16585443 ER PT J AU Kessler, RC Adler, L Barkley, R Biederman, J Conners, CK Demler, O Faraone, SV Greenhill, LL Howes, MJ Secnik, K Spencer, T Ustun, TB Walters, EE Zaslavsky, AM AF Kessler, RC Adler, L Barkley, R Biederman, J Conners, CK Demler, O Faraone, SV Greenhill, LL Howes, MJ Secnik, K Spencer, T Ustun, TB Walters, EE Zaslavsky, AM TI The prevalence and correlates of adult ADHD in the United States: Results from the National Comorbidity Survey Replication SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; WORLD-HEALTH-ORGANIZATION; FAMILIAL SUBTYPE; PSYCHIATRIC STATUS; ANXIETY DISORDERS; ECONOMIC BURDEN; BIPOLAR DISORDER; CONDUCT DISORDER; SELF-RATINGS AB Objective: Despite growing interest in adult attention deficit hyperactivity disorder ( ADHD), little is known about its prevalence or correlates. Method: A screen for adult ADHD was included in a probability subsample ( N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD. Results: The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders. Conclusions: Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NYU, Med Ctr, Dept Neurol, New York, NY 10016 USA. NYU, Med Ctr, Dept Psychiat, New York, NY 10016 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. SUNY Syracuse, Upstate Med Univ, Med Genet Res Ctr, Syracuse, NY USA. SUNY Syracuse, Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. Columbia Univ, Div Child & Adolescent Psychiat, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Eli Lilly & Co, Global Hlth Outcomes, Indianapolis, IN 46285 USA. WHO, Global Burden Dis Unit, Boston, MA USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM kessler@hcp.med.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [U01 MH060220, U01 MH060220-04, U01-MH-60220] NR 62 TC 1418 Z9 1444 U1 25 U2 206 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2006 VL 163 IS 4 BP 716 EP 723 DI 10.1176/appi.ajp.163.4.716 PG 8 WC Psychiatry SC Psychiatry GA 029EF UT WOS:000236541200026 PM 16585449 ER PT J AU Ahn, AC Ngo-Metzger, Q Legedza, ATR Massagli, MP Clarridge, BR Phillips, RS AF Ahn, AC Ngo-Metzger, Q Legedza, ATR Massagli, MP Clarridge, BR Phillips, RS TI Complementary and alternative medical therapy use among Chinese and Vietnamese Americans: Prevalence, associated factors, and effects of patient-clinician communication SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PRIMARY-CARE PERFORMANCE; ETHNIC-DIFFERENCES; ASIAN-AMERICANS; UNITED-STATES; HEALTH; MINORITIES; RATINGS AB Objective. We examined the use of complementary and alternative medical (CAM) therapies among Chinese and Vietnamese Americans who had limited proficiency with the English language and explore the association between patient-clinician discussions about CAM therapy use and patient assessments of quality of care. Methods. We surveyed Chinese and Vietnamese Americans who visited 11 community health centers in 8 major cities throughout the United Stateds. Results. Of the 4410 patients surveyed, 3258 (74%) returned completed questionnaires. Two thirds of respondents reported they had "ever used" some form of CAM therapy; however, only 7.6% of these patients had discussed their use of CAM therapies with clinicians. Among patients who had used CAM therapies during the week before their most recent visits, clinician-patient discussions about CAM therapy use were associated with better overall patient ratings oi quality of care. Conclusion. Use of CAM therapies was common among Chinese and Vietnamese Americans who had limited proficiency with the English language. Although discussions about CAM therapy use with clinicians were uncommon, these discussions were associated with better ratings of quality of care. C1 Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Univ Calif Irvine, Coll Med, Irvine, CA 92717 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Ahn, AC (reprint author), Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, 401 Pk Dr,Ste 22A W, Boston, MA 02215 USA. EM aahn@hms.harvard.edu FU AHRQ HHS [R01 HS010316, 1R01HS10316]; NCCIH NIH HHS [T32-AT0051-03, K24-AT000589, T32 AT000051, K24 AT000589] NR 30 TC 45 Z9 46 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2006 VL 96 IS 4 BP 647 EP 653 DI 10.2105/AJPH.2004.048496 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027QD UT WOS:000236429200025 PM 16380575 ER PT J AU Jett, JR Miller, YE AF Jett, JR Miller, YE TI Update in lung cancer 2005 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID GROWTH-FACTOR RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; SPIRAL COMPUTED-TOMOGRAPHY; ENDOSCOPIC ULTRASOUND; EXHALED BREATH; GEFITINIB; MUTATIONS; CHEMOTHERAPY; ASPIRATION; RESISTANCE C1 Denver Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, Denver, CO 80220 USA. Mayo Coll Med, Rochester, MN USA. Univ Colorado, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO USA. RP Miller, YE (reprint author), Denver Vet Affairs Med Ctr, Pulm & Crit Care Med Sect, 111A,1055 Clermot St, Denver, CO 80220 USA. EM miller@uchsc.edu NR 35 TC 5 Z9 5 U1 0 U2 0 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 APR 1 PY 2006 VL 173 IS 7 BP 695 EP 697 DI 10.1164/rccm.2601008 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 029AQ UT WOS:000236530600002 PM 16556699 ER PT J AU Zacharia, TT Saini, S Halpern, EF Sumner, JE AF Zacharia, TT Saini, S Halpern, EF Sumner, JE TI CT of colon cancer metastases to the liver using modified RECIST criteria: Determining the ideal number of target lesions to measure SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 90th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY MAY 07, 2004 CL Chicago, IL SP Radiol Soc N Amer DE cancer; colon; CT; liver; metastases; oncologic imaging ID RESPONSE EVALUATION CRITERIA; SOLID TUMORS RECIST; GUIDELINES; LUNG AB OBJECTIVE. We sought to define the ideal number of target lesions to be measured to assess disease response in patients undergoing chemotherapy for colon cancer metastases to the liver. MATERIALS AND METHODS. Thirty consecutive patients were recruited for this study. Patients were part of a multisite, randomized, double-ami, phase 3 clinical trial involving chemotherapy with an investigational drug for metastatic colon cancer. Patients were recruited from U.S. and international sites. Institutional review board approval was obtained, and informed consent was obtained from all patients. Our study included CT measurements of hepatic metastases. All patients (n = 30) had a minimum of five target lesions in the liver. Target-lesion size was defined by Response Evaluation Criteria in Solid Tumors (RECTST) criteria. We calculated the patient response at 2 months and at 6 months (complete response, partial response, stable disease, and progressive disease) using RECIST. Patient response was calculated based on the percentage increase or decrease at 2 and 6 months in the greatest diameter of the single largest lesion, two large lesions, three large lesions, four lesions, and five lesions, respectively. The concordance between five-target-lesion measurement and lesser numbers of lesions was analyzed using kappa statistics (StatView, 5.0). RESULTS. In 93.33% of patients (n = 28/30), there was agreement on patient response irrespective of the number of measurements made on CT. Of these 30 patients, 47% had a partial response (n = 14/30), 43% had stable disease (n = 13/30), and 10% had progressive disease at 2 months (n = 3/30). At 6 months, 43% had a partial response (n = 13/30) 47% had stable disease (n = 14/30), and 10% had progressive disease (n = 3/30). Agreement in response evaluation between lesion groups for multiple measurements was high, with values of 1.0 for multiple-lesion measurements and 0.88 for single-lesion measurements at 2 months. The concordance values were the same at 6 months. CONCLUSION. In the majority of patients with hepatic metastases of colorectal cancer, measuring the maximal diameter of the single largest lesion yielded the same treatment-response classification as measuring up to five target lesions. This result suggests that it may be possible to reduce the number of lesions measured in clinical trials. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Zacharia, TT (reprint author), 4225 Ithaca St, Elmhurst, NY 11373 USA. EM ttz100@hotmail.com OI Zacharia, Thomas/0000-0002-6908-9440 NR 16 TC 27 Z9 28 U1 0 U2 1 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 APR PY 2006 VL 186 IS 4 BP 1067 EP 1070 DI 10.2214/AJR.05.0038 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 026DD UT WOS:000236316000026 PM 16554580 ER PT J AU Jones, SE Belsley, NA McLoud, TC Mullins, ME AF Jones, SE Belsley, NA McLoud, TC Mullins, ME TI Rheumatoid meningitis: Radiologic and pathologic correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE neuroimaging; rheumatoid arthritis; rheumatoid meningitis ID ARTHRITIS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Jones, SE (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 216,55 Fruit St, Boston, MA 02114 USA. EM sejones@partners.org NR 5 TC 20 Z9 21 U1 0 U2 1 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 APR PY 2006 VL 186 IS 4 BP 1181 EP 1183 DI 10.2214/AJR.05.0859 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 026DD UT WOS:000236316000047 PM 16554601 ER PT J AU Rollins, SE Young, RH Bell, DA AF Rollins, SE Young, RH Bell, DA TI Autoimplants in serous borderline tumors of the ovary - A clinicopathologic study of 30 cases of a process to be distinguished from serous adenocarcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE serous borderline tumor; ovary; ovarian implants; ovarian carcinoma ID DIAGNOSTIC-CRITERIA; CRIBRIFORM PATTERNS; FOLLOW-UP; MICROPAPILLARY; CARCINOMA; IMPLANTS AB The clinical and pathologic features of serous borderline tumors (SBTs) with autoimplants (AIs) were studied with emphasis on their relation to survival, ovarian SBT with a micropapillary pattern, and their distinction from serous adenocarcinoma. The 30 patients ranged in age from 17 to 70 years (mean, 35.8 years). Two had stage I disease, 10 had stage 11 disease, and IS had stage III disease. Twenty-five patients had bilateral ovarian tumors. In 28 cases, AIs were present on the surface of the neoplasm or between exophytic surface tumor papillae, in 2 cases, AIs were between papillae within intracystic tumor. The AIs consisted of single cells or glands and clusters of cells with mild to moderate nuclear atypia within a fibroblastic stroma; the stroma dominated over the epithelium in extent within the AI. In many cases, the epithelial cells in the AI had abundant eosinophilic cytoplasm. All but 2 of the patients had coexisting noninvasive peritoneal implants; 3 of them also had invasive peritoneal implants. Six of the SBTs had a micropapillary pattern; 3 of these were stage III and 3 stage 11 tumors. Clinical follow-up was available for 11 patients. Eight were alive and well after 4 to 7 years (mean, 5 years); 3 of these patients had stage II disease and 5 had stage III disease. Three were dead of disease after 7 to 12 years (mean, 9 years). Two patients who died of disease had stage III disease, and 1 of them had invasive implants. The third patient had stage II disease, invasive implants, and the tumor was of the rnicropapillary type. Our study indicates that the majority of patients with SBT with AI have stage II or III disease and abundant exophytic tumor. SBTs with AI had a micropapillary pattern in 20% of the cases. AIs do not appear to have an adverse impact on survival when controlled for peritoneal implant type and for this reason must be distinguished from true stromal invasion in serous carcinoma, a misdiagnosis sometimes made, or seriously entertained, initially in these cases. Features that favor AI over carcinoma arising in an SBT are 1) a location between tumor papillae or on the ovarian surface 2) a predominance of stroma over epithelial cells, and 3) the "borderline" cytologic appearance of epithelial cells. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rollins, SE (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Lab, 55 Fruit St, Boston, MA 02114 USA. EM srollins@partners.org NR 23 TC 10 Z9 10 U1 0 U2 0 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 APR PY 2006 VL 30 IS 4 BP 457 EP 462 DI 10.1097/00000478-200604000-00005 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 033US UT WOS:000236876500005 PM 16625091 ER PT J AU Koulmanda, M Smith, RN Qipo, A Weir, G Auchincloss, H Strom, TB AF Koulmanda, M Smith, RN Qipo, A Weir, G Auchincloss, H Strom, TB TI Prolonged survival of allogeneic islets in cynomolgus monkeys after short-term anti-CD154-based therapy: Nonimmunologic graft failure? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE allograft; autografts; cynomologlus monkeys; islet transplantation ID CHRONIC-PANCREATITIS; NONHUMAN-PRIMATES; TRANSPLANTATION; TOLERANCE; AUTOTRANSPLANTATION; DONOR; CELLS; IMPLANTATION; TRANSFUSION; AUTOGRAFTS AB Conventional drug therapy and several anti-CD154 mAb-based regimens were tested in the nonhuman primate (NHP) islet allograft model and found to be inadequate because islets were lost to rejection. Short-term therapy with an optimized donor-specific transfusion (DST) + rapamycin (RPM) + anti-CD154 mAb regimen enables immunosuppression drug-free islet allograft function for months following cessation of therapy in the NHP islet allograft model. After a substantial period of drug-free graft function, these allografts slowly and progressively lost function. Pathologic studies failed to identify islet allograft rejection as a destructive islet invasive lymphocytic infiltration of the allograft was not detected. To evaluate the mechanism, immunologic versus nonimmunologic, of the late islet allograft loss in hosts receiving the optimized therapeutic regimen, we performed experiments with islet autografts and studied islet function in NHPs with partial pancreatectomy. The results in both experiments utilizing autologous islet allografts and partially pancreatectomized hosts reinforce the view that the presence of a marginal islet mass leads to slowly progressive nonimmunological islet loss. Long-term clinically successful islet cell transplantation cannot be realized in the absence of parallel improvements in tolerizing regimens and in the preparation of adequate numbers of islets. C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Islet Transplantat Res Lab, Transplant Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Transplant Res Ctr, Div Immunol, Boston, MA 02215 USA. RP Koulmanda, M (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM koulmand@helix.mgh.harvard.edu FU NIAID NIH HHS [5 R01 AI50987, R01 AI050987]; NIDDK NIH HHS [P01 DK53087] NR 23 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2006 VL 6 IS 4 BP 687 EP 696 DI 10.1111/j.1600-6143.2006.01235.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 019ME UT WOS:000235839900008 PM 16539625 ER PT J AU Munene, G Graham, JA Holt, RW Johnson, LB Marshall, HP AF Munene, G Graham, JA Holt, RW Johnson, LB Marshall, HP TI Biliary-colonic fistula: A case report and literature review SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southeastern-Surgical-Congress CY FEB 11-15, 2005 CL New Orleans, LA SP SE Surg Congress ID BILE-DUCT INJURIES; LAPAROSCOPIC CHOLECYSTECTOMY; HEPATOBILIARY SCINTIGRAPHY; MANAGEMENT; EXPERIENCE AB We report the occurrence of common bile duct obstruction and biliary-colonic fistula after open cholecystectomy. Although it is a very unusual complication after cholecystectomy, biliary-colonic fistula should be part of the differential diagnosis for patients presenting with sepsis after open or laparoscopic cholecystectomy. After confirmation and characterization of the injury by endoscopic retrograde cholangiopancreatography and cholangiogram, assessment for undrained collections by computed tomography scan, control of sepsis and coagulopathy, and nutritional support, surgical repair was undertaken. The patient underwent fistula take-down between the common bile duct and the colon at the hepatic flexure, primary closure of the colon enterotomy, and a Roux-en-Y end-to-side hepaticojejunostomy at the confluence of the right and left hepatic ducts. Recovery was uneventful and the patient was doing well at the 6-month follow-up. Surgical repair should be undertaken by surgeons with extensive experience in hepatobiliary reconstruction. C1 Georgetown Univ Hosp, Dept Surg, Washington, DC 20007 USA. RP Munene, G (reprint author), Massachusetts Gen Hosp, JCK 812,55 Fruit St, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 30 TC 4 Z9 4 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD APR PY 2006 VL 72 IS 4 BP 347 EP 350 PG 4 WC Surgery SC Surgery GA 032QC UT WOS:000236788400015 PM 16676862 ER PT J AU Lee, DJ de Venecia, RK Guinan, JJ Brown, MC AF Lee, DJ de Venecia, RK Guinan, JJ Brown, MC TI Central auditory pathways mediating the rat middle ear muscle reflexes SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE acoustic reflex; stapedius; tensor tympani; inter-neuron; cochlear nucleus ID VENTRAL COCHLEAR NUCLEUS; PHYSIOLOGICAL-RESPONSE PROPERTIES; PRODUCT OTOACOUSTIC EMISSIONS; TENSOR TYMPANI MOTONEURONS; HORSERADISH-PEROXIDASE; STAPEDIUS-MUSCLE; ACOUSTIC REFLEX; KAINIC ACID; INFERIOR COLLICULUS; NEURONAL ORGANIZATION AB The middle ear muscle (MEM) reflexes function to protect the inner ear from intense acoustic stimuli and to reduce acoustic masking. Sound presented to the same side or to the opposite side activates the MEM reflex on both sides. The ascending limbs of these pathways must be the auditory nerve fibers originating in the cochlea and terminating in the cochlear nucleus, the first relay station for all ascending auditory information. The descending limbs project from the motoneurons in the brainstem to the MEMs on both sides, causing their contraction. Although the ascending and descending pathways are well described, the cochlear nucleus interneurons that mediate these reflex pathways have not been identified. In order to localize the MEM reflex interneurons, we developed a physiologically based reflex assay in the rat that can be used to determine the integrity of the reflex pathways after experimental manipulations. This assay monitored the change in tone levels and distortion product otoacoustic emissions within the ear canal in one ear during the presentation of a reflex-eliciting sound stimulus in the contralateral ear. Preliminary findings using surgical transection and focal lesioning of the auditory brainstem to interrupt the MEM reflexes suggest that MEM reflex interneurons are located in the ventral cochlear nucleus. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Univ Massachusetts, Mem Med Ctr, Dept Otolaryngol, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM daniel_lee@meei.harvard.edu FU NIDCD NIH HHS [1 K08 DC06285-01, DC01089, K08 DC006285] NR 92 TC 14 Z9 15 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD APR PY 2006 VL 288A IS 4 BP 358 EP 369 DI 10.1002/ar.a.20296 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA 032MY UT WOS:000236779900006 PM 16550576 ER PT J AU Lovich, MA Kinnealley, ME Sims, NM Peterfreund, RA AF Lovich, MA Kinnealley, ME Sims, NM Peterfreund, RA TI The delivery of drugs to patients by continuous intravenous infusion: Modeling predicts potential dose fluctuations depending on flow rates and infusion system dead volume SO ANESTHESIA AND ANALGESIA LA English DT Article ID SYRINGE PUMPS; NITROPRUSSIDE; PERFORMANCE; IMPACT; SIZE AB IV drug infusion has the potential for dosing errors, which arise from complex interactions between carrier flows and the infusion set dead volume. We computed the steady-state mass of drug stored in the infusion set dead volume, using phenylephrine as a model compound. The mass of drug in the dead volume increases with stock drug concentration and desired dose but decreases with carrier flow rate. We also modeled the dynamic perturbations in drug delivery when a carrier is abruptly stopped. Rapid initial carrier flow rates lead to greater depression in drug delivery rate after carrier flow ceases. Rapid drug infusion rates lead to faster restoration of desired drug delivery. Finally, the time to reach a new steady-state after a change in drug delivery or carrier rate was computed. This time is longest for large stock-drug concentrations, larger dead volumes, and slower final carrier rates. These computations illustrate that (a) the dead volume may contain a large mass of drug available for inadvertent bolus, (b) cessation of carrier flow can profoundly reduce drug delivery, and (c) after a change in carrier flow or drug dosing, a significant lag is possible before drug delivery achieves steady state. Although computed for phenylephrine, the concepts are generic and valid for any drug administered by IV infusion. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biomed Engn, Boston, MA 02114 USA. RP Lovich, MA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mlovich@partners.org NR 16 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2006 VL 102 IS 4 BP 1147 EP 1153 DI 10.1213/01.ane.0000198670.02481.6b PG 7 WC Anesthesiology SC Anesthesiology GA 026VO UT WOS:000236371100030 PM 16551914 ER PT J AU Martyn, J Durieux, ME AF Martyn, J Durieux, ME TI Succinylcholine - New insights into mechanisms of action of an old drug SO ANESTHESIOLOGY LA English DT Editorial Material ID ACETYLCHOLINE-RECEPTORS; EXPRESSION; DIAPHRAGM; SUBUNITS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Biochem Pharmacol Lab, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. Univ Virginia, Dept Anesthesiol, Charlottesville, VA USA. Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. RP Martyn, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Biochem Pharmacol Lab, Boston, MA 02114 USA. EM jmartyn@etherdome.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM31569-23, R01 GM055082, P50 GM2500-25, R01 GM55082-08] NR 14 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2006 VL 104 IS 4 BP 633 EP 634 DI 10.1097/00000542-200604000-00004 PG 2 WC Anesthesiology SC Anesthesiology GA 027PX UT WOS:000236428600003 PM 16571955 ER PT J AU Kobayashi, H Walzer, TB Gardner, R Pian-Smith, MC Raemer, DB AF Kobayashi, H Walzer, TB Gardner, R Pian-Smith, MC Raemer, DB TI Explicit communication in an obstetrical emergency SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY APR 26-30, 2006 CL Hollywood, FL SP Soc Obstet Anesthesia & Perinatol C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2006 VL 104 IS 4 BP B14 EP B14 PG 1 WC Anesthesiology SC Anesthesiology GA 027PX UT WOS:000236428600062 ER PT J AU O'Shea, AG Peterfreund, R Tsen, L Charnin, J Leffert, L Pian-Smith, M AF O'Shea, AG Peterfreund, R Tsen, L Charnin, J Leffert, L Pian-Smith, M TI Peripheral venous pressure as a comparison of loss of resistance hemodynamic variable in pregnant patients undergoing spinal anesthesia SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY APR 26-30, 2006 CL Hollywood, FL SP Soc Obstet Anesthesia & Perinatol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2006 VL 104 IS 4 BP B8 EP B8 PG 1 WC Anesthesiology SC Anesthesiology GA 027PX UT WOS:000236428600050 ER PT J AU Sun, BC Mohanty, SA Weiss, R Tadeo, R Hasbrouck, M Koenig, W Meyer, C Asch, S AF Sun, BC Mohanty, SA Weiss, R Tadeo, R Hasbrouck, M Koenig, W Meyer, C Asch, S TI Effects of hospital closures and hospital characteristics on emergency department ambulance diversion, Los Angeles County, 1998 to 2004 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT National Meeting of the Robert Wood Johnson Clinical Scholars Program CY NOV, 2005 CL Ft Lauderdale, FL ID CONSEQUENCES; CAPACITY; TRENDS; DELAYS AB Study objective: We assess the effects of nearby hospital closures and other hospital characteristics on emergency department (ED) ambulance diversion. Methods: The study design was a retrospective, multiple interrupted time series with control group. We studied all ambulance-receiving hospitals with EDs in Los Angeles County from 1998 to 2004. The main outcome measure was monthly ambulance diversion hours because of ED saturation. Results: Our sample included 80 hospitals, of which 9 closed during the study period. There were increasing monthly diversion hours over time, from an average of 57 hours (95% confidence interval [CI] 51 to 63 hours) in 1998 to 190 hours (95% CI 180 to 200 hours) in 2004. In multivariate modeling, hospital closure increased ambulance monthly diversion hours by an average of 56 hours (95% CI 28 to 84 hours) for 4 months at the nearest ED. County-operated hospitals had 150 hours (95% Cl 90 to 200 hours) and trauma centers had 48 hours (95% CI 9 to 87 hours) more diversion than other hospitals. Diversion hours for a given facility were positively correlated with diversion hours of the nearest ED (0.3; 95% CI 0.28 to 0.32). There was a significant and positive interaction between diversion hours of the nearest ED and time, suggesting that the effects of an adjacent facility's diversion hours increased during the study period. Conclusion: Hospital closure was associated with a significant but transient increase in ambulance diversion for the nearest ED. The temporal trend toward more diversion hours, as well as increasing effects of the nearest facility's diversion hours over time, implies that the capacity to absorb future hospital closures is declining. C1 Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. Univ So Calif, Dept Med, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. Los Angeles Cty Emergency Med Serv Agcy, Los Angeles, CA USA. W Los Angeles Vet Affairs Local Ctr, Dept Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RP Sun, BC (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, 911 Broxton Ave, Los Angeles, CA 90024 USA. EM bsun@post.harvard.edu NR 23 TC 38 Z9 38 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2006 VL 47 IS 4 BP 309 EP 316 DI 10.1016/j.annemergmed.2005.12.003 PG 8 WC Emergency Medicine SC Emergency Medicine GA 029IH UT WOS:000236555300001 PM 16546614 ER PT J AU Sampson, HA Munoz-Furlong, A Campbell, RL Adkinson, NF Bock, SA Branum, A Brown, SGA Camargo, CA Cydulka, R Galli, SJ Gidudu, J Gruchalla, RS Harlor, AD Hepner, DL Lewis, LM Lieberman, PL Metcalfe, DD O'Connor, R Muraro, A Rudman, A Schmitt, C Scherrer, D Simons, FE Thomas, S Wood, JP Decker, WW AF Sampson, HA Munoz-Furlong, A Campbell, RL Adkinson, NF Bock, SA Branum, A Brown, SGA Camargo, CA Cydulka, R Galli, SJ Gidudu, J Gruchalla, RS Harlor, AD Hepner, DL Lewis, LM Lieberman, PL Metcalfe, DD O'Connor, R Muraro, A Rudman, A Schmitt, C Scherrer, D Simons, FE Thomas, S Wood, JP Decker, WW TI Second Symposium on the Definition and Management of Anaphylaxis: Summary report - Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; EPINEPHRINE ABSORPTION; PEANUT; SHOCK; CHILDREN; MODEL; FOOD; EPIDEMIOLOGY; MULTICENTER; ADOLESCENTS C1 Mayo Clin, Rochester, MN 55905 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Food Allergy & Anaphylaxis Network, Fairfax, VA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Food Allergy & Anaphylaxis Network, Boulder, CO USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Fremantle Hosp, Fremantle, WA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Ctr Dis Control & Prevent, Lilbum, GA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Amer Acad Pediat, Eugene, OR USA. Amer Soc Anesthesiol, Boston, MA USA. Soc Acad Emergency Med, St Louis, MO USA. Amer Coll Allergy Asthma & Immunol, Cordova, TN USA. NIAID, Bethesda, MD 20892 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Natl Assoc EMS Physicians, Baltimore, MD USA. Univ Padua, I-35100 Padua, Italy. Amer Acad Allergy Asthma & Immunol, Winnipeg, MB, Canada. Amer Coll Emergency Physicians, Dallas, TX USA. Amer Acad Emergency Med, Scottsdale, AZ USA. RP Decker, WW (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM decker.wyatt@mayo.edu RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Brown, Simon/0000-0002-9961-0890 NR 47 TC 161 Z9 168 U1 0 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD APR PY 2006 VL 47 IS 4 BP 373 EP 380 DI 10.1016/j.annemergmed.2006.01.018 PG 8 WC Emergency Medicine SC Emergency Medicine GA 029IH UT WOS:000236555300013 PM 16546624 ER PT J AU Ayata, C Jin, HW Kudo, C Dalkara, T Moskowitz, MA AF Ayata, C Jin, HW Kudo, C Dalkara, T Moskowitz, MA TI Suppression of cortical spreading depression in migraine prophylaxis SO ANNALS OF NEUROLOGY LA English DT Article ID RAT CEREBRAL-CORTEX; SODIUM VALPROATE; MAGNETIC STIMULATION; HEMIPLEGIC MIGRAINE; TRIGEMINAL NUCLEUS; CALCIUM-CHANNELS; CONTROLLED-TRIAL; FUNCTIONAL MRI; VISUAL-CORTEX; BRAIN-TISSUE AB Objective: Topiramate, valproate, propranolol, amitriptyline, and methysergide have been widely prescribed for migraine prophylaxis, but their mechanism or site of action is uncertain. Cortical spreading depression (CSD) has been implicated in migraine and as a headache trigger and can be evoked in experimental animals by electrical or chemical stimulation. We hypothesized that migraine prophylactic agents suppress CSD as a common mechanism of action. Methods: Rats were treated either acutely or chronically over weeks and months, with one of the above migraine prophylactic drugs, vehicle, or D-propranolol, a clinically ineffective drug. The impact of treatment was determined on the frequency of evoked CSDs after topical potassium application or on the incremental cathodal stimulation threshold to evoke CSD. Results. Chronic daily administration of migraine prophylactic drugs dose-dependently suppressed CSD frequency by 40 to 80% and increased the cathodal stimulation threshold, whereas acute treatment was ineffective. Longer treatment durations produced stronger CSD suppression. Chronic D-propranolol treatment did not differ from saline control. Interpretation Our data suggest that CSD provides a common therapeutic target for widely prescribed migraine prophylactic drugs. Assessing CSD threshold may prove useful for developing new prophylactic drugs and improving upon existing ones. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurosci Intens Care Unit, Charlestown, MA 02129 USA. Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. EM moskowitz@helix.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [P01 NS35611] NR 79 TC 279 Z9 292 U1 1 U2 28 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2006 VL 59 IS 4 BP 652 EP 661 DI 10.1002/ana.20778 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029ZZ UT WOS:000236604200015 PM 16450381 ER PT J AU Klein, AM Pierce, MC Zeitels, SM Anderson, RR Kobler, JB Shishkov, M de Boer, JF AF Klein, AM Pierce, MC Zeitels, SM Anderson, RR Kobler, JB Shishkov, M de Boer, JF TI Imaging the human vocal folds in vivo with optical coherence tomography: A preliminary experience SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 13-14, 2005 CL Boca Raton, FL SP Amer Laryngol Assoc DE glottis; laryngeal imaging; optical coherence tomography; vocal fold ID BIREFRINGENCE; FEASIBILITY; CARCINOMA; MUCOSA AB Objectives: Optical coherence tomography (OCT) and polarization-sensitive OCT (PS-OCT) are promising noninvasive methods for in vivo, cross-sectional imaging of the microstructure of the vocal folds. Previous studies in other tissues have shown an axial resolution of less than 10 mu m and a maximum imaging depth of about 2 mm. The objectives of this pilot study were to obtain images from the vocal folds of subjects who were being evaluated and/or treated for vocal fold disease and to evaluate how well normal and pathologic microstructure could be seen in these images. Methods: Twenty-six vocal folds in 13 subjects were imaged with a flexible OCT probe. The images were successfully collected from subjects who were either topically anesthetized or under general anesthesia for microlaryngoscopic procedures. Results: The thickness of the epithelium, the relative collagen content of the subepithelial connective tissue, and certain characteristic features of lesions (including cysts, scarring, and papilloma) were seen in the OCT and PS-OCT images. Conclusions: "Live microscopy" of the human vocal folds is very promising for improved diagnosis. mapping, and treatment planning. To our knowledge, this study is the first application of PS-OCT for in vivo imaging of the human vocal folds. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. RP de Boer, JF (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,Bar 724, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCRR NIH HHS [R01-RR212039] NR 19 TC 25 Z9 27 U1 0 U2 2 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 APR PY 2006 VL 115 IS 4 BP 277 EP 284 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 033BJ UT WOS:000236820900005 PM 16676824 ER PT J AU Sarac, S McKenna, MJ Mikulec, AA Rauch, SD Nadol, JB Merchant, SN AF Sarac, S McKenna, MJ Mikulec, AA Rauch, SD Nadol, JB Merchant, SN TI Results after revision stapedectomy with malleus grip prosthesis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE conductive hearing loss; malleus; prosthesis; revision; stapedectomy ID STAPES SURGERY; HEARING AB Revision stapedectomy with a malleus grip prosthesis is a technically challenging otologic procedure. The prosthesis is usually longer and extends deeper into the vestibule than a conventional stapes prosthesis, creating the potential to affect the vestibular sense organs. The prosthesis also bypasses the ossicular joints, which are thought to play a role in protecting the inner car from large changes in static pressure within the middle ear. The prosthesis is in close proximity to the tympanic membrane, thus increasing the risk for its extrusion. We reviewed our experience with revision stapedectomy with the Schuknecht Teflon-wire malleus grip prosthesis in 36 ears with a mean follow-up of 23 months. The air-bone gap was closed to within 10 dB in 16 ears (44%) and to within 20 dB in 26 ears (72%). The incidence of postoperative sensorineural hearing loss was 8% (3 ears). There were no dead cars. Extrusion of the prosthesis occurred in 1 case (3%). Nearly 50% of patients reported various degrees of vertigo or disequilibrium during the first 3 weeks after surgery. These vestibular symptoms resolved by 6 weeks in all but I case. We did not find evidence of damage to the inner ear due to the length of the prosthesis or due to the potential for direct transmission of changes in static pressures within the middle ear to the labyrinth. Our results are similar to those published in the literature for malleus attachment stapedectomy and conventional revision incus stapedectomy. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC004798, DC 04798, R01 DC004798-06] NR 16 TC 7 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 APR PY 2006 VL 115 IS 4 BP 317 EP 322 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 033BJ UT WOS:000236820900012 PM 16676830 ER PT J AU Margenthaler, JA Longo, WE Virgo, KS Johnson, FE Grossmann, EM Schifftner, TL Henderson, WG Khuri, SF AF Margenthaler, JA Longo, WE Virgo, KS Johnson, FE Grossmann, EM Schifftner, TL Henderson, WG Khuri, SF TI Risk factors for adverse outcomes following surgery for small bowel obstruction SO ANNALS OF SURGERY LA English DT Article ID SMALL INTESTINAL-OBSTRUCTION; AFFAIRS SURGICAL RISK; NONOPERATIVE TREATMENT; VETERAN POPULATION; HOSPITAL VOLUME; MORTALITY-RATE; ADHESIVE; QUALITY; CARE; ADJUSTMENT AB Objective: To construct risk indices predicting adverse outcomes following surgery for small bowel obstruction (SBO). Methods: The VA National Surgical Quality Improvement Program contains prospectively collected data oil more than I million patients. Patients undergoing adhesiolysis only or small bowel resection for SBO from 1991 to 2002 were selected. Independent variables included 68 presurgical and 12 intraoperative risk factors; dependent variables were 21 adverse Outcomes including death. Stepwise logistic regression was used to construct models predicting 30-day morbidity and mortality and to derive risk index values. Patients were then divided into risk classes. Results: Of the 2002 patients, 1650 underwent adhesiolysis only and 352 underwent small bowel resection. Thirty-seven percent undergoing adhesiolysis only and 47% undergoing small bowel resection had more than I complication (P < 0.001). The overall 30-day mortality was 7.7% and did not differ significantly between the groups. Odds of death were highest for dirty or infected Wounds, ASA class 4 or 5, age > 80 years, and dyspnea at rest. Morbidity ranged from 22%, among patients with 0 to 7 risk points, to 62% for those with > 19 risk points. Mortality ranged from 2% among patients with 0 to 12 risk points to 28% for those with > 31 risk points. Conclusions: Morbidity and mortality after surgery for SBO in VA hospitals are comparable with those in other large series. The morbidity rate, but not the mortality rate, is significantly higher in patients requiring small bowel resection compared with those requiring adhesiolysis only (P < 0.001). The risk indices presented provide all easy-to-use tool for clinicians to predict outcomes for patients undergoing surgery for SBO. C1 Yale Univ, Med Ctr, Dept Surg, New Haven, CT 06520 USA. Washington Univ, Sch Med, St Louis, MO USA. St Louis Univ, Sch Med, St Louis, MO USA. St Louis VA Med Ctr, St Louis, MO USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Denver VA Med Ctr, Denver, CO USA. Harvard Univ, Sch Med, Boston, MA USA. Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. RP Longo, WE (reprint author), Yale Univ, Med Ctr, Dept Surg, 330 Cedar St, New Haven, CT 06520 USA. EM walter.longo@yale.edu NR 39 TC 49 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 2006 VL 243 IS 4 BP 456 EP 464 DI 10.1097/01.sla.0000205668.58519.76 PG 9 WC Surgery SC Surgery GA 029AN UT WOS:000236530300005 PM 16552195 ER PT J AU Binstadt, BA Nguyen, LT Huang, H Bronson, R Benoist, C Mathis, D AF Binstadt, B. A. Nguyen, L. T. Huang, H. Bronson, R. Benoist, Ch. Mathis, D. TI Spontaneous cardiac valve inflammation in the K/BxN murine arthritis model SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 26th European Workshop for Rheumatology Research CY APR 23, 2006 CL Glasgow, SCOTLAND C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Binstadt, Bryce/N-1305-2013 OI Binstadt, Bryce/0000-0003-3127-3856 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD APR PY 2006 VL 65 SU 1 MA 070 BP A23 EP A23 PG 1 WC Rheumatology SC Rheumatology GA 210XV UT WOS:000249489800071 ER PT J AU Pessler, F Dai, L Einhorn, E Cron, RQ Schumacher, HR AF Pessler, F. Dai, L. Einhorn, E. Cron, R. Q. Schumacher, H. R. TI Overexpression of the calcium-calcineurin-NFAT signaling pathway in rheumatoid arthritis synovium SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 26th European Workshop for Rheumatology Research CY APR 23, 2006 CL Glasgow, SCOTLAND C1 Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Sun Yat Sen Univ, Guangzhou, Guangdong, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD APR PY 2006 VL 65 SU 1 MA 069 BP A23 EP A23 PG 1 WC Rheumatology SC Rheumatology GA 210XV UT WOS:000249489800070 ER PT J AU Mangi, AA Torchiana, DF AF Mangi, AA Torchiana, DF TI Ascending aortic pseudoaneurysm in a patient without a sternum SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Surg Unit, Bullfinch 208,55 Fruit St, Boston, MA 02114 USA. EM dtorchiana@partners.org 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2006 VL 81 IS 4 BP 1517 EP 1517 DI 10.1016/j.athoracsur.2004.05.034 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 025BB UT WOS:000236239200068 PM 16564314 ER PT J AU Jacoby, GA Walsh, KE Mills, DM Walker, VJ Oh, H Robicsek, A Hooper, DC AF Jacoby, GA Walsh, KE Mills, DM Walker, VJ Oh, H Robicsek, A Hooper, DC TI qnrB, another plasmid-mediated gene for quinolone resistance SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SPECTRUM BETA-LACTAMASES; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; FLUOROQUINOLONE RESISTANCE; TRANSFERABLE PLASMID; PROTEIN; CIPROFLOXACIN; DNA AB A novel plasmid-mediated quinolone resistance gene, qnrB, has been discovered in a plasmid encoding the CTX-M-15 beta-lactamase from a klebsiella pneumoniae strain isolated in South India. It has less than 40% amino acid identity with the original qnr (now qnrA) gene or with the recently described qnrS but, like them, codes for a protein belonging to the pentapeptide repeat family. Strains with qnrB demonstrated low-level resistance to all quinolones tested. The gene has been cloned in an expression vector attaching a polyhistidine tag, which facilitated purification to >= 95% homogeneity. As little as 5 pM of QnrB-His(6) protected purified DNA gyrase against inhibition by 2 mu g/ml (6 mu M) ciprofloxacin. With a PCR assay qnrB has been detected in Citrobacter koseri, Enterobacter cloarae, and Escherichia coli isolates from the United States, linked to SHV-12 beta-lactamase and coding for a product differing in five amino acids from the Indian (now QnrB1) variety, The qnrB gene has been found near Orf1005 in some, but not all, plasmids and in association with open reading frames matching known chromosomal genes, suggesting that it too was acquired by plasmids from an as-yet-unknown bacterial source. C1 Lahey Clin Fdn, Burlington, MA 01805 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), Lahey Clin Fdn, 41 Mall Rd, Burlington, MA 01805 USA. EM george.a.jacoby@lahey.org FU NIAID NIH HHS [R01 AI057576, AI43312, AI57576, R01 AI043312] NR 20 TC 249 Z9 295 U1 3 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2006 VL 50 IS 4 BP 1178 EP 1182 DI 10.1128/AAC.50.4.1178-1182.2006 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700009 PM 16569827 ER PT J AU Tegos, GP Anbe, M Yang, CM Demidova, TN Satti, M Mroz, P Janjua, S Gad, F Hamblin, MR AF Tegos, GP Anbe, M Yang, CM Demidova, TN Satti, M Mroz, P Janjua, S Gad, F Hamblin, MR TI Protease-stable polycationic photosensitizer conjugates between polyethyleneimine and chlorin(e6) for broad-spectrum antimicrobial photoinactivation SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GRAM-NEGATIVE BACTERIA; TARGETED PHOTODYNAMIC THERAPY; OUTER-MEMBRANE; IN-VIVO; EFFICIENT PHOTOSENSITIZERS; WOUND INFECTIONS; ESCHERICHIA-COLI; OXYGEN RADICALS; SINGLET OXYGEN; INACTIVATION AB We previously showed that covalent conjugates between poly-L-lysine and chlorin(e6) were efficient photosensitizers (PS) of both gram-positive and gram-negative bacteria. The polycationic molecular constructs increased binding and penetration of the PS into impermeable gram-negative cells. We have now prepared a novel set of second-generation polycationic conjugates between chlorin(e6) and three molecular forms of polyethyleneimine (PEI): a small linear, a small cross-linked, and a large cross-linked molecule. The conjugates were characterized by high-pressure liquid chromatography and tested for their ability to kill a panel of pathogenic microorganisms, the gram-positive Staphylococcus aureus and Streptococcus pyogenes, the gramnegative Escherichia coli and Pseudomonas aeruginosa, and the yeast Candida albicans, after exposure to low levels of red light. The large cross-linked molecule efficiently killed all organisms, while the linear conjugate killed gram-positive bacteria and C. albicans. The small cross-linked conjugate was the least efficient antimicrobial PS and its remarkably low activity could not be explained by reduced photochemical quantum yield or reduced cellular uptake. In contrast to polylysine conjugates, the PEI conjugates were resistant to degradation by proteases such as trypsin that hydrolyze lysine-lysine peptide bonds, The advantage of protease stability combined with the ready availability of PEI suggests these molecules may be superior to polylysine-PS conjugates for photodynamic therapy of localized infections. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Engn, Dept Mat Sci & Engn, Tokyo, Japan. Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Grad Program Cell Mol & Dev Biol, Boston, MA 02111 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Aga Khan Med Sch, Karachi, Pakistan. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R01 CA083882, R01 CA083882-01A2, R01 CA083882-02, R01 CA083882-03]; NIAID NIH HHS [R01 AI050875, R01 AI050875-04, R01 AI050875-05A1, R01AI050875] NR 49 TC 101 Z9 104 U1 4 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2006 VL 50 IS 4 BP 1402 EP 1410 DI 10.1128/AAC.50.4.1402-1410.2006 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700040 PM 16569858 ER PT J AU Kirkpatrick, WR Coco, BJ Patterson, TF AF Kirkpatrick, WR Coco, BJ Patterson, TF TI Sequential or combination antifungal therapy with voriconazole and liposomal amphotericin B in a guinea pig model of invasive aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EFFICACY; ITRACONAZOLE; ANTAGONISM AB We evaluated combinations of voriconazole (VRC) and liposomal amphotericin B (L-AMB) in a guinea pig invasive aspergillosis model. Simultaneous VRC and L-AMB was most effective, although VRC monotherapy was also effective. These regimens as well as sequential L-AMB followed by VRC were more effective than L-AMB alone or VRC followed by L-AMB. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphys Div, San Antonio, TX 78284 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. EM kirkpatrick@uthscsa.edu NR 12 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2006 VL 50 IS 4 BP 1567 EP 1569 DI 10.1128/AAC.50.4.1567-1569.2006 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 031EA UT WOS:000236685700069 PM 16569887 ER PT J AU Freeman, S Francis, S Lundahl, K Bowland, T Dellavalle, RP AF Freeman, S Francis, S Lundahl, K Bowland, T Dellavalle, RP TI UV tanning advertisements in high school newspapers SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol ID BASAL-CELL; POPULATION; CANCERS; RISK AB Objective: To examine the increasing use of UV tanning parlors by adolescents, despite the World Health Organization recommendation that no one under the age of 18 years use UV tanning devices. Design: We examined tanning advertisements in a sample of public high school newspapers published between 2001 and 2005 in 3 Colorado counties encompassing the Denver metropolitan area. Results: Tanning advertisements appeared in newspapers from 11 (48%) of 23 schools. Newspaper issues (N= 131) contained 40 advertisements placed by 18 tanning parlors. Advertisements commonly offered discounts ( 19 of 40) including unlimited tanning offers ( 15 of 40). Thirteen advertisements featured non-UV tanning treatments, and 2 advertisements mentioned parental consent or accompaniment for UV tanning. Conclusions: UV radiation, a classified carcinogen, is commonly and specifically marketed to adolescents through high school newspaper advertising. Public health skin cancer prevention policies should include the prohibition of UV tanning advertising to minors. C1 Denver Vet Affairs Med Ctr, Dermatol Serv, Denver, CO 80220 USA. Univ Colorado Denver, Hlth Sci Ctr, Dept Dermatol, Aurora, CO USA. RP Dellavalle, RP (reprint author), Denver Vet Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Mail Code 165, Denver, CO 80220 USA. EM robert.dellavalle@uchsc.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X FU NCI NIH HHS [K-07CA92550] NR 9 TC 22 Z9 22 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2006 VL 142 IS 4 BP 460 EP 462 DI 10.1001/archderm.142.4.460 PG 3 WC Dermatology SC Dermatology GA 033NG UT WOS:000236854700007 PM 16618865 ER PT J AU Johnson, KR Heilig, LF Hester, EJ Francis, SO Deakyne, SJ Dellavalle, RP AF Johnson, KR Heilig, LF Hester, EJ Francis, SO Deakyne, SJ Dellavalle, RP TI Indoor tanning attitudes and practices of US dermatologists compared with other medical specialists SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Society-of-Preventive-Oncology CY MAR 13-15, 2005 CL San Francisco, CA SP Amer Soc Prevent Oncol ID CUTANEOUS MALIGNANT-MELANOMA; SUN PROTECTION; RISK; PEDIATRICIANS; BEHAVIOR; EXPOSURE; CHILDREN AB Objective: To compare the indoor tanning attitudes and practices of dermatologists with physicians in other medical specialties ( internal medicine, pediatrics, and family medicine) commonly providing sun safety counseling to patients. Design: Cross-sectional study. Setting: Questionnaire mailed to randomly selected US dermatologists, internists, family practitioners, and pediatricians. Results: The overall response rate was 38% (364/949): 71% indicated that patients had asked their opinions about indoor UV tanning, 80% believed that UV tanning was unsafe, and 90% agreed they would counsel patients against nonmedical indoor UV tanning. Many supported increased UV tanning legislation, including minimum age restrictions (91%) and parental consent requirements ( 90%). Dermatologists were significantly more likely than other physicians to respond to the survey (52% vs 31%, P <. 001), speak with patients about indoor UV tanning ( odds ratio [ OR], 26.5; 95% confidence interval [CI], 9.5-74.1]), believe that indoor UV tanning is unsafe OR, 14.0; 95% CI, 5.0- 39.4), and support increased regulation ( OR, 11.7; 95% CI, 1.5- 88.5). Women discouraged indoor UV tanning more than men ( OR, 5.2; 95% CI, 1.8-15.2). Physicians who had used indoor UV tanning (19%) more often agreed that non-UV tanning lotion ( OR, 2.0; 95% CI, 1.1-3.8) and airbrush tanning ( OR, 1.9; 95% CI, 1.1-3.4) were safe but did not differ in attitudes regarding UV tanning safety. Physicians practicing in the Northeast and Midwest were more likely to support UV tanning to improve mood ( OR, 2.0; 95% CI, 1.1-3.5) and more commonly believed that UV tanning could help treat depression ( OR, 2.6; 95% CI, 1.5-4.6) or prevent vitamin D deficiency ( OR, 1.7; 95% CI, 1.0-2.8). Conclusions: Physicians, especially dermatologists, are frequently asked about and generally discourage indoor UV tanning. Dermatologists regard indoor UV tanning more negatively compared with other physicians. Physician sex and geographic location were associated with specific indoor UV tanning attitudes. C1 Univ Colorado, Dept Dermatol, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Dellavalle, RP (reprint author), Denver Vet Affairs Med Ctr, Dermatol Serv, 1055 Clermont St,Mail Code 165, Denver, CO 80220 USA. EM robert.dellavalle@uchsc.edu RI Dellavalle, Robert/L-2020-2013 OI Dellavalle, Robert/0000-0001-8132-088X FU NCI NIH HHS [CA92550]; NIAMS NIH HHS [T32 AR07411] NR 18 TC 10 Z9 10 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2006 VL 142 IS 4 BP 465 EP 470 DI 10.1001/archderm.142.4.465 PG 6 WC Dermatology SC Dermatology GA 033NG UT WOS:000236854700008 PM 16618866 ER PT J AU Lim, JL Solky, BA Sober, AJ Duncan, LM AF Lim, JL Solky, BA Sober, AJ Duncan, LM TI An erythematous and pigmented lesion of the abdomen - Malignant melanoma, superficial spreading type (pink area), and lentiginous junctional dysplastic nevus with slight cytologic atypia (brown area). SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MELANOCYTIC NEVI; BIOPSY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lim, JL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2006 VL 142 IS 4 BP 515 EP 516 DI 10.1001/archderm.142.4.515-e PG 2 WC Dermatology SC Dermatology GA 033NG UT WOS:000236854700019 PM 16618876 ER PT J AU Cohen, LS Soares, CN Vitonis, AF Otto, MW Harlow, BL AF Cohen, LS Soares, CN Vitonis, AF Otto, MW Harlow, BL TI Risk for new onset of depression during the menopausal transition - The Harvard study of moods and cycles SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; HOT FLASHES; POSTMENOPAUSAL WOMEN; PERIMENOPAUSAL WOMEN; MAJOR DEPRESSION; BREAST-CANCER; PSYCHIATRIC MORBIDITY; REPLACEMENT THERAPY; LIFE AB Context: Transition to menopause has long been considered a period of increased risk for depressive symptoms. However, it is unclear whether this period is one of increased risk for major depressive disorder, particularly for women who have not had a previous episode of depression. Objective: To examine the association between the menopausal transition and onset of first lifetime episode of depression among women with no history of mood disturbance. Design: Longitudinal, prospective cohort study. Setting: A population-based cross-sectional sample. Participants: Premenopausal women, 36 to 45 years of age, with no lifetime diagnosis of major depression (N = 460), residing in 7 Boston, Mass, metropolitan area communities. Main Outcome Measure: Incidence of new onset of depression based on structured clinical interviews, Center for Epidemiologic Studies Depression Scale scores, and an operational construct for depression. Results: Premenopausal women with no lifetime history of major depression who entered the perimeno-pause were twice as likely to develop significant depressive symptoms as women who remained premenopausal, after adjustment for age at study enrollment and history of negative life events. The increased risk for depression was somewhat greater in women with self-reported vasomotor symptoms. Conclusions: The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness. C1 Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Cohen, LS (reprint author), Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. EM lcohen2@partners.org NR 56 TC 314 Z9 335 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2006 VL 63 IS 4 BP 385 EP 390 DI 10.1001/archpsyc.63.4.385 PG 6 WC Psychiatry SC Psychiatry GA 031TG UT WOS:000236726400006 PM 16585467 ER PT J AU Wiggs, JL AF Wiggs, JL TI Complement factor H and macular degeneration - The genome yields an important clue SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID DISEASE; POLYMORPHISM; PATHWAY; VARIANT; COMMON; RISK; ACID C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 16 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2006 VL 124 IS 4 BP 577 EP 578 DI 10.1001/archopht.124.4.577 PG 2 WC Ophthalmology SC Ophthalmology GA 031CB UT WOS:000236680600020 PM 16606888 ER PT J AU Renshaw, AA Wang, E Haja, J Wilbur, D Henry, MR Hughes, JH AF Renshaw, AA Wang, E Haja, J Wilbur, D Henry, MR Hughes, JH CA Cytopathology Comm TI Fine-needle aspiration of papillary thyroid carcinoma - Distinguishing between cases that performed well and those that performed poorly in the college of American pathologists nongynecologic cytology program SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID FOLLOW-UP; BIOPSY; DIAGNOSIS; MANAGEMENT; CRITERIA; NODULES; NEOPLASM; DILEMMA; DISEASE AB Context.-Although the cytologic features of papillary thyroid carcinoma in fine-needle aspiration specimens are well known, the correlation of these features with the ability of cytologists to identify this tumor has not been well studied. Objective.-To compare the cytologic features of cases of papillary thyroid carcinoma that performed poorly with those of cases that performed well. Design.-The cytologic features of 13 cases of papillary thyroid carcinoma from the College of American Pathologists Nongynecologic Cytology Program that performed poorly were compared with those of 15 cases that performed well. Results.-Compared with cases that performed well, cases that performed poorly were significantly more likely to lack marked nuclear enlargement (38% vs 100%, P <.001), lack pale chromatin (8% vs 47%, P =.04), and lack intranuclear inclusions (8% vs 53%, P =. 02). The differences between the 2 groups in staining, type of preparation, nuclear grooves, nuclear crowding, colloid, cellularity, nuclear pleomorphism, and Hurthle cell change were not significant. Conclusions.-Cases of papillary thyroid carcinoma that lack marked nuclear enlargement, pale chromatin, and intranuclear inclusions are significantly more difficult to recognize than cases that have these features. Increased awareness of these types of cases might improve the performance of thyroid fine-needle aspiration in clinical practice. C1 Baptist Hosp Miami, Dept Pathol, Miami, FL 33176 USA. Coll Amer Pathologists, Northfield, IL USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cleveland Clin, Dept Pathol & Lab Med, Naples, FL USA. Lab Med Consultants Ltd, Las Vegas, NV USA. RP Renshaw, AA (reprint author), Baptist Hosp Miami, Dept Pathol, 8900 N Kendall Dr, Miami, FL 33176 USA. EM andrewr@baptisthealth.net NR 27 TC 9 Z9 10 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2006 VL 130 IS 4 BP 452 EP 455 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 032LZ UT WOS:000236777200005 PM 16594737 ER PT J AU Ma, XJ Patel, R Wang, XQ Salunga, R Murage, J Desai, R Tuggle, JT Wang, W Chu, S Stecker, K Raja, R Robin, H Moore, M Baunoch, D Sgroi, D Erlander, M AF Ma, XJ Patel, R Wang, XQ Salunga, R Murage, J Desai, R Tuggle, JT Wang, W Chu, S Stecker, K Raja, R Robin, H Moore, M Baunoch, D Sgroi, D Erlander, M TI Molecular classification of human cancers using a 92-gene real-time quantitative polymerase chain reaction assay SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID GENE-EXPRESSION DATA; CDNA MICROARRAY DATA; UNKNOWN PRIMARY SITE; METASTATIC ADENOCARCINOMA; ORIGIN; IDENTIFICATION; NORMALIZATION; CARCINOMAS; SIGNATURES; MARKERS AB Context.-Correct diagnosis of the tissue origin of a metastatic cancer is the first step in disease management, but it is frequently difficult using standard pathologic methods. Microarray-based gene expression profiling has shown great promise as a new tool to address this challenge. Objective.-Adoption of microarray technologies in the clinic remains limited. We aimed to bridge this technological gap by developing a real-time quantitative polymerase chain reaction (RT-PCR) assay. Design.-We constructed a microarray database of 466 frozen and 112 formalin-fixed, paraffin-embedded (FFPE) samples of both primary and metastatic tumors, measuring expression of 22000 genes. From the microarray database, we used a genetic algorithm to search for gene combinations optimal for multitumor classification. A 92-gene RT-PCR assay was then designed and used to generate a database for 481 frozen and 119 FFPE tumor samples. Results.-The microarray-based K-nearest neighbor classifier demonstrated 84% accuracy in classifying 39 tumor types via cross-validation and 82% accuracy in predicting 112 independent FFPE samples. We successfully translated the microarray database to the RT-PCR platform, which allowed an overall success rate of 87% in classifying 32 different tumor classes in the validation set of 119 FFPE tumor samples. Conclusions.-The RT-PCR-based expression assay involving 92 genes represents a powerful tool for accurately and objectively identifying the site of origin for metastatic tumors, especially in the cases of cancer of unknown primary. The assay uses RT-PCR and routine FFPE samples, making it suitable for rapid clinical adoption. C1 Arcturus BioSci Inc, Res & Dev, Mountain View, CA 92008 USA. US Labs, Res & Dev, Irvine, CA USA. Sharp Mem Hosp & Rehabil Ctr, Dept Pathol, San Diego, CA 90034 USA. Harvard Univ, Sch Med, Dept Pathol, Mol Pathol Res Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Erlander, M (reprint author), Arcturus BioSci Inc, 2715 Loker Ave,W, Carlsbad, CA 92008 USA. EM merlander@arcturusdx.com NR 29 TC 127 Z9 131 U1 0 U2 5 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2006 VL 130 IS 4 BP 465 EP 473 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 032LZ UT WOS:000236777200008 PM 16594740 ER PT J AU Primack, BA Gold, MA Switzer, GE Hobbs, R Land, SR Fine, MJ AF Primack, BA Gold, MA Switzer, GE Hobbs, R Land, SR Fine, MJ TI Development and validation of a smoking media literacy scale for adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID TOBACCO USE; CIGARETTE-SMOKING; UNITED-STATES; PROMOTION; SUSCEPTIBILITY; PREVENTION; INITIATION; INDUSTRY; TRIAL; FILMS AB Objectives: To develop a smoking media literacy (SML) scale by using empiric survey data from a large sample of high school students and to assess reliability and criterion validity of the scale. Design: On the basis of an established theoretical framework, 120 potential items were generated, and items were eliminated or altered on the basis of input from experts and students. Cross-sectional responses to scale items, demographics, smoking-related variables, and multiple covariates were obtained to refine the scale and determine its reliability and validity. Setting: One large Pittsburgh, Pa, high school. Participants: A total of 1211 high school students aged 14 to 18 years. Main Outcome Measures: Current smoking, susceptibility to smoking, attitudes toward smoking, and smoking norms. Results: Factor analysis demonstrated a strong 1-factor scale with 18 items (alpha=0.87). After controlling for all co-variate data, SML had a statistically significant and independent association with current smoking (P=.01), susceptibility (P<.001), and attitudes (P<.001), but not norms (P=.42). Controlling for all covariates, an increase of 1 point on the 10-point SML scale was associated with a 22% decrease in the odds of being a smoker and a 31% decrease in the odds of being susceptible to smoking. Conclusions: Smoking media literacy can be measured with excellent reliability and concurrent criterion validity. Given the independent association between SML and smoking, media literacy may be a promising tool for future tobacco control interventions. C1 Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Div Adolescent Med, Pittsburgh, PA 15213 USA. Temple Univ, Sch Commun & Theater, Philadelphia, PA 19122 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equin Res & Promot, Pittsburgh, PA USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, 230 McKee Pl,Suite 600,Room 4, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NCI NIH HHS [K07 CA114315, K07 CA114315-01A1] NR 37 TC 32 Z9 32 U1 5 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2006 VL 160 IS 4 BP 369 EP 374 DI 10.1001/archpedi.160.4.369 PG 6 WC Pediatrics SC Pediatrics GA 028VI UT WOS:000236516500005 PM 16585481 ER PT J AU Lee, SW Kim, WJ Park, JA Choi, YK Kwon, YW Kim, KW AF Lee, SW Kim, WJ Park, JA Choi, YK Kwon, YW Kim, KW TI Blood-brain barrier interfaces and brain tumors SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE blood-brain barrier; brain angiogenesis; barriergenesis; tight junctions; oxygen tension; glioblastoma ID ENDOTHELIAL GROWTH-FACTOR; HUMAN GLIOBLASTOMA-MULTIFORME; JUNCTIONAL ADHESION MOLECULE; TIGHT JUNCTION; GLUCOSE-TRANSPORTER; IN-VIVO; DEVELOPMENTAL EXPRESSION; DIABETIC-RETINOPATHY; VESSEL DEVELOPMENT; OXYGEN-TENSION AB In the developing brain, capillaries are differentiated and matured into the blood-brain barrier (BBB), which is composed of cerebral endothelial cells, astrocyte end-feet, and pericytes. Since the BBB regulates the homeostasis of central nervous system (CNS), the maintenance of the BBB is important for CNS function. The disruption of the BBB may result in many brain disorders including brain tumors. However, the molecular mechanism of BBB formation and maintenane is poorly understood. Here, we summarize recent advances in the role of oxygen tension and growth factors on BBB development and maintenance, and in BBB dysfunction related with brain tumors. C1 Seoul Natl Univ, Neurovasc Coordinat Res Ctr, Coll Pharm, Seoul 151742, South Korea. Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul 151742, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02129 USA. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. RP Kim, KW (reprint author), Seoul Natl Univ, Neurovasc Coordinat Res Ctr, Coll Pharm, Seoul 151742, South Korea. EM qwonkim@plaza.snu.ac.kr NR 100 TC 30 Z9 32 U1 1 U2 5 PU PHARMACEUTICAL SOCIETY KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD APR PY 2006 VL 29 IS 4 BP 265 EP 275 DI 10.1007/BF02968569 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 038DK UT WOS:000237198500001 PM 16681030 ER PT J AU Sepahpanah, F Burns, SP McKnight, B Yang, CC AF Sepahpanah, F Burns, SP McKnight, B Yang, CC TI Role of creatinine clearance as a screening test in persons with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Spinal-Injury-Association CY MAY 13, 2005 CL Dallas, TX SP Amer Spinal Injury Assoc DE bladder; neurogenic; creatinine; kidney function tests; rehabilitation; reproducibility of results; spinal cord injuries ID GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; RENAL-FUNCTION; CYSTATIN-C AB Objectives: To determine (1) the variability of annual creatinine clearance (C-Cr) testing for subjects with chronic spinal cord injury (SCI) and (2) whether decisions to change neurogenic bladder management are made based on C-Cr. measurements. Design: Retrospective chart review. Setting: Inpatient Veterans Affairs SCI unit. Participants: The medical records of 70 men were consecutively selected for review from among 664 veterans enrolled in the SCI clinic. All patient charts had to have at least 5 C-Cr tests performed within 10 years preceding the review. Interventions: Not applicable. Main Outcome Measures: Development of renal insufficiency and change in medical or bladder management of the patient, based on the results of the C-Cr test. Results: For individual patients, the results of 24-hour C-Cr were highly variable from 1 evaluation to the next; the within-subject standard deviation (SD) for C-Cr was 25.9mL/min. The within-subject SD for serum creatinine was 0.12mg/dL. For all comparisons of repeatability, variability, and reliability, serum creatinine was superior to C-Cr. No medical management decisions were made based on the result of the 24-hour creatinine clearance. Renal ultrasound results and postvoid bladder residuals were the major factors in changing medical management with regard to renal function preservation. Conclusions: The Cc, test has little value as a screening measure for renal disease in SCI patients because of its variability in serial testing. C1 VA Puget Sound Hlth Care Syst, Urol Sect, Spinal Cord Injury Unit, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Yang, CC (reprint author), VA Puget Sound Hlth Care Syst, Urol Sect, Spinal Cord Injury Unit, 1660 S Columbian Way,S112-UR, Seattle, WA 98108 USA. EM cyang@u.washington.edu FU NCIPC CDC HHS [R49/CE000197] NR 20 TC 14 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2006 VL 87 IS 4 BP 524 EP 528 DI 10.1016/j.apmr.2005.11.032 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 036BL UT WOS:000237045800010 PM 16571392 ER PT J AU Cosimi, AB AF Cosimi, AB TI Surgeons and the Nobel Prize SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the New-England-Surgical-Society CY OCT 02, 2005 CL Bretton Woods, NH SP New England Surg Soc ID WINNERS; CASTRATION; CARCINOMA; PROSTATE; CANCER C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, 55 Fruit St, Boston, MA 02114 USA. EM cpadyk@partners.org NR 24 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 340 EP 348 DI 10.1001/archsurg.141.4.340 PG 9 WC Surgery SC Surgery GA 032HT UT WOS:000236766200002 PM 16618890 ER PT J AU Bamboat, ZM Berger, DL AF Bamboat, ZM Berger, DL TI Is right hemicolectoray for 2.0-cm appendiceal carcinoids justified? SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the New-England-Surgical-Society CY OCT 02, 2005 CL Bretton Woods, NH SP New England Surg Soc ID TUMORS AB Hypothesis: We believe right hemicolectomy (RHC) is not necessary in patients with an appendiceal carcinoid greater than 2.0 cm. Design: A retrospective review of patients with a histologically confirmed appendiceal carcinoid from April 1, 1980, to February 28, 2005, and an analysis of the literature. Setting: Tertiary care referral center. Patients: Forty-eight patients (34 females and 14 males) with a histologically confirmed diagnosis of appendiceal carcinoid were included in the study. Appendiceal carcinoid was diagnosed incidentally in all 48 patients. Patient ages ranged from 11 to 86 years (mean age, 41 years). Postoperative follow-up and disease-free survival were confirmed in 33 patients via medical record review. Main Outcome Measures: We assessed the relationship between survival, tumor size, and the role of RHC vs appendectomy alone. Results: Four patients in our series underwent secondary RHC and lymph node dissection for tumors greater than 2.0 cm, and none had positive lymph nodes. Following review of the literature, we were unable to find any recent evidence of distant metastasis from carcinoids in patients already treated by appendectomy. There seem to be no conclusive data to support the notion that RHC confers a survival benefit over appendectomy for carcinoids greater than 2.0 cm. Conclusion: Appendiceal carcinoids greater than 2.0 cm can be managed effectively with simple appendectomy, given their low malignant potential and slow growth, obviating the need for RHC in this group of patients without affecting overall survival. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. EM dberger@partners.org NR 17 TC 33 Z9 36 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 349 EP 352 DI 10.1001/archsurg.141.4.349 PG 4 WC Surgery SC Surgery GA 032HT UT WOS:000236766200003 PM 16618891 ER PT J AU Rodriguez, JR Germes, SS Pandharipande, PV Gazelle, GS Thayer, SP Warshaw, AL Fernandez-del Castillo, CFD AF Rodriguez, JR Germes, SS Pandharipande, PV Gazelle, GS Thayer, SP Warshaw, AL Fernandez-del Castillo, CFD TI Implications and cost of pancreatic leak following distal pancreatic resection SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the New-England-Surgical-Society CY OCT 02, 2005 CL Bretton Woods, NH SP New England Surg Soc ID CONTROLLED-TRIAL; OCTREOTIDE; FISTULA; COMPLICATIONS; PREVENTION; MULTICENTER; PANCREATICODUODENECTOMY; MORTALITY; EFFICACY; SURGERY AB Objectives: Pancreatic stump leak (PL) after elective distal pancreatic resection significantly impacts cost and increases subsequent health care resource utilization. We sought to provide an economic framework for potential interventions aimed at reducing its occurrence. Design: Retrospective case series and economic evaluation. Setting: University-affiliated, tertiary care referral center. Patients: Sixty-six patients undergoing elective distal pancreatectomy. Main Outcome Measures: Postoperative complications; hospital and professional costs. Results: Overall postoperative morbidity occurred in 34 patients (52%) with no deaths. The total number of patients with complications directly related to PL was 22 (33%). The meant +/- SD number of total hospital days for the no-PL group was 5.2 +/- 1.7 days (range, 3-12 days) vs 16.6 +/- 14.6 days (range, 4-49 days) for the PL group (P=.001). The average patient with PL-related problems incur-red a total cost that was 2.01 times greater than the average patient in the no-PL group. A decision analytic model developed to evaluate threshold costs showed that a hypothetical intervention designed to reduce the complication rate of distal pancreatectomy by one third would be financially justifiable up to a cost of $1418 per patient. Conclusions: Complications derived from PL following distal pancreatectomy double the cost and dramatically increase health care resource utilization. There is an urgent need to develop strategies that reduce the incidence of this common complication. Interventions aimed at decreasing the incidence of PL should take into account this cost differential. We provide an economic model to serve as a guide for developing these technologies. C1 Massachusetts Gen Hosp, Dept Surg, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fernandez-del Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, Ctr Clin Effectiveness Surg, 15 Parkman St,WACC 336, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08 DK071329] NR 25 TC 82 Z9 87 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 361 EP 365 DI 10.1001/archsurg.141.4.361 PG 5 WC Surgery SC Surgery GA 032HT UT WOS:000236766200007 PM 16618893 ER PT J AU Sokal, SM Craft, DL Chang, YC Sandberg, WS Berger, DL AF Sokal, SM Craft, DL Chang, YC Sandberg, WS Berger, DL TI Maximizing operating room and recovery room capacity in an era of constrained resources SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the New-England-Surgical-Society CY OCT 02, 2005 CL Bretton Woods, NH SP New England Surg Soc ID ANESTHESIA; INDUCTION AB Hypothesis: Three parallel processing operating rooms (ORs) (concurrent induction and turnover) with a dedicated 3-bed mini-recovery room (mini-postanesthesia care unit [PACU]) will optimize patient throughput and main PACU workload when compared with 4 traditional ORs or 4 parallel processing ORs. Design: Statistical and mathematical models projected the impact of parallel processing on case throughput and PACU use. Setting: Academic medical center with 48 traditional ORs using serial induction and turnover and 1 experimental OR, the operating room of the future, with parallel processing. Participants: All surgical cases from October 2002 through March 2004 (N = 49 887). Interventions: A statistical model projected the duration of induction, surgery, turnover, and PACU stay for cases performed in a traditional OR (n = 48 667) based on the operating room of the future (n = 1220) experience. A fluid queuing model compared each combination using specific probability density functions. Main Outcome Measures: Each OR configuration was evaluated for case throughput and minutes of work sent to the PACU. Results: Although all cases save OR time with parallel processing, only select surgeon-case combinations translate time saved into additional cases per day (26%). Without additional PACU slots, output from 4 parallel processing ORs further stresses the PACU. Three parallel processing ORs and a mini-PACU balances incremental volume by offsetting PACU utilization in 84% of cases. Conclusion: In a PACU-constrained environment, 3 parallel processing ORs with a mini-PACU configuration offers increased throughput and decreased PACU workload. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang 465, Boston, MA 02114 USA. EM dberger@partners.org NR 7 TC 25 Z9 25 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 389 EP 393 DI 10.1001/archsurg.141.4.389 PG 5 WC Surgery SC Surgery GA 032HT UT WOS:000236766200017 PM 16618898 ER PT J AU Donahoe, PK AF Donahoe, PK TI Genomic approaches to surgical diseases - 21st Annual Samuel Jason Mixter Lecture SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the New-England-Surgical-Society CY SEP 30-OCT 02, 2005 CL Bretton Woods, NH SP New England Surg Soc ID CONGENITAL DIAPHRAGMATIC-HERNIA; LUNG DEVELOPMENT; MORBIDITY; MICE C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Simches Res Bldg,CPZN 6-203,185 Cambridge St, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 409 EP 413 DI 10.1001/archsurg.141.4.409 PG 5 WC Surgery SC Surgery GA 032HT UT WOS:000236766200025 PM 16618902 ER PT J AU Ferguson, CM Warshaw, AL AF Ferguson, CM Warshaw, AL TI Failure of a Web-based educational tool to improve residents' scores on the American Board of Surgery In-Training Examination SO ARCHIVES OF SURGERY LA English DT Article ID EXAM ABSITE; PERFORMANCE; IMPACT AB Hypothesis: Usage of a Web-based educational tool will improve residents' scores on the American Board of Surgery In-Training Examination (ABSITE). Design: Before and after trial. Setting: Academic surgical residency in a tertiary care university hospital. Participants: Nineteen postgraduate year 1 (PGY1) and PGY2 residents. Intervention: All PGY1 and PGY2 residents were given unlimited access to a Web-based educational tool aimed at early-level residents in surgery. The educational tool covers the basic science of surgery and basic concepts of clinical surgery and uses a variety of educational techniques (readings, problem-based learning, case-based learning, and practice tests). Although residents were encouraged to complete the learning package, they were not required to do so. Main Outcome Measures: The ABSITE scores and changes in ABSITE scores were compared with the amount of time residents spent using the program and the number of tutorials completed. Results: There was no significant difference in ABSITE scores before or after the use of the Web-based educational tool. There was no significant relationship between use of the tool (either in total time or total tutorials) and ABSITE score. For PGY2 residents, there was a negative relationship between total time spent on the program and ABSITE score (linear regression analysis best-fit slope, -0.20 +/- 0.1; r(2) = 0.33) and total tutorials completed and ABSITE score (linear regression analysis best-fit slope, -0.34 +/- 0.22; r(2) = 0.25). Conclusion: There was no demonstrable beneficial effect of a Web-based educational tool on cognitive knowledge of residents as measured by ABSITE scores. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ferguson, CM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM cferguson@partners.org NR 9 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2006 VL 141 IS 4 BP 414 EP 416 DI 10.1001/archsurg.141.4.414 PG 3 WC Surgery SC Surgery GA 032HT UT WOS:000236766200026 PM 16622938 ER PT J AU He, ZH Opland, DM Way, KJ Ueki, K Bodyak, N Kang, PM Izumo, S Kulkarni, RN Wang, B Liao, RL Kahn, CR King, GL AF He, ZH Opland, DM Way, KJ Ueki, K Bodyak, N Kang, PM Izumo, S Kulkarni, RN Wang, B Liao, RL Kahn, CR King, GL TI Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiomyocyte; collateral circulation; diabetes; insulin resistance; vascularization; VEGF ID OBESE ZUCKER RATS; DIABETIC CARDIOMYOPATHY; DIFFERENTIALLY AFFECTS; SIGNALING PATHWAYS; CARDIAC-FUNCTION; CELLS; ANGIOGENESIS; ANGIOTENSIN; INFARCTION; MUSCLE AB Objective-This study characterized the role of insulin receptors and resistance on vascular endothelial growth factor (VEGF) expression and myocardial vascularization in physiological conditions and after ischemia. Methods and Results-Cardiac microvascular density was reduced by 30% in insulin-resistant Zucker fatty rats versus lean controls. This was associated with a parallel 40% inhibition of insulin-stimulated activation of both Akt and VEGF expression in the myocardium and cardiomyocytes. In contrast, the activation of Erk1/2 by insulin remained unchanged. In cultured cardiomyocytes, insulin or insulin-like growth factor (IGF)-1 increased VEGF mRNA and protein expression by 2-fold. Inhibition of PI3K/Akt, especially Akt2-mediated cascades but not the Ras/MEK/Erk pathway, using chemical inhibitors, dominant negative adenoviral constructs, or siRNA approaches suppressed VEGF mRNA expression by insulin. Ventricular tissues from muscle insulin receptor knockout (MIRKO) mice, which lack insulin receptors in the myocardium, have significant reductions in insulin but not IGF-1 signaling, VEGF expression, and vascular density before and after ischemia versus controls. Conclusions-Insulin regulates VEGF gene expression and vascularization in the myocardium specifically via insulin receptors and the activation of PI3K/Akt pathway. Selective inhibition of this pathway may lead to the decreases in VEGF expression and capillary density in the myocardium of patients with insulin resistance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiovasc Inst, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [DK02885-03, R01 DK53105, R01 DK59725] NR 31 TC 49 Z9 58 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2006 VL 26 IS 4 BP 787 EP 793 DI 10.1161/01.ATV.0000209500.15801.4e PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 024VA UT WOS:000236223200017 PM 16469952 ER PT J AU Cohen, PL AF Cohen, PL TI Stopping traffic in Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID CHEMOKINES C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Cohen, PL (reprint author), Univ Penn, 421 Curie Blvd,Room 757, Philadelphia, PA 19104 USA. EM philipco@mail.med.upenn.edu NR 9 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2006 VL 54 IS 4 BP 1061 EP 1062 DI 10.1002/art.21746 PG 2 WC Rheumatology SC Rheumatology GA 033EZ UT WOS:000236830800006 PM 16572440 ER PT J AU Mao, HZ Roussos, EI Peterfy, M AF Mao, HZ Roussos, EI Peterfy, M TI Genetic analysis of the diabetes-prone C57BLKS/J mouse strain reveals genetic contribution from multiple strains SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE type 2 diabetes mellitus; animal model; C57BLKS mouse strain; leptin receptor mutation; microsatellite marker ID EXPRESSION; LOCUS; MUTATIONS; MICE; ATHEROSCLEROSIS; SUSCEPTIBILITY; HAPLOTYPE; C57BL/6J; OBESITY AB The C57BLKS/J (BKS) inbred mouse strain is a widely used animal model of type 2 diabetes. In the presence of the diabetes (db) mutation, obese BKS-db mice develop severe diabetes. Genetic studies of diabetes-susceptibility in this strain are facilitated by the fact that BKS is a genetic composite between the diabetes-resistant C57BL/6J (136) and susceptible DBA/2J (DBA) strains. On this basis, it has been hypothesized that diabetes-susceptibility in BKS is conferred by DBA-derived alleles. However, recent studies revealed non-B6/non-DBA genetic material in BKS. To identify the origin of this genetic component, we generated a genomic map of BKS using 537 microsatellite markers. Our results demonstrate that, in addition to B6 and DBA, BKS contains alleles from at least three other strains, including 129, C57BL/10 and an unidentified mouse strain. We also analyzed two congenic strains, B6-db and BKS-db, which are widely used for the genetic mapping of diabetes-susceptibility loci. We identified several donor-derived genomic regions introduced during the generation of these congenic strains. In summary, our study reveals novel aspects of the genetic fine-structure of BKS and related strains and facilitates the identification of diabetes-susceptibility loci in this mouse model. (C) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Peterfy, M (reprint author), Univ Calif Los Angeles, Dept Med, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. EM mpeterfy@ucla.edu FU NIDDK NIH HHS [R01-DK071673] NR 20 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD APR PY 2006 VL 1762 IS 4 BP 440 EP 446 DI 10.1016/j.bbidis.2006.01.002 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 026CM UT WOS:000236314300007 PM 16481151 ER PT J AU Whetzel, PL Parkinson, H Causton, HC Fan, LJ Fostel, J Fragoso, G Game, L Heiskanen, M Morrison, N Rocca-Serra, P Sansone, SA Taylor, C White, J Stoeckert, CJ AF Whetzel, PL Parkinson, H Causton, HC Fan, LJ Fostel, J Fragoso, G Game, L Heiskanen, M Morrison, N Rocca-Serra, P Sansone, SA Taylor, C White, J Stoeckert, CJ TI The MGED Ontology: a resource for semantics-based description of microarray experiments SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; DATABASE; INFORMATION; EXCHANGE AB Motivation: The generation of large amounts of microarray data and the need to share these data bring challenges for both data management and annotation and highlights the need for standards. MIAME specifies the minimum information needed to describe a microarray experiment and the Microarray Gene Expression Object Model (MAGE-OM) and resulting MAGE-ML provide a mechanism to standardize data representation for data exchange, however a common terminology for data annotation is needed to support these standards. Results: Here we describe the MGED Ontology (MO) developed by the Ontology Working Group of the Microarray Gene Expression Data (MGED) Society. The MO provides terms for annotating all aspects of a microarray experiment from the design of the experiment and array layout, through to the preparation of the biological sample and the protocols used to hybridize the RNA and analyze the data. The MO was developed to provide terms for annotating experiments in line with the MIAME guidelines, i.e. to provide the semantics to describe a microarray experiment according to the concepts specified in MIAME. The MO does not attempt to incorporate terms from existing ontologies, e.g. those that deal with anatomical parts or developmental stages terms, but provides a framework to reference terms in other ontologies and therefore facilitates the use of ontologies in microarray data annotation. C1 Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, MRC, Ctr Clin Sci, London W12 0NN, England. Ontol Workshop LLC, Columbia, MD 21045 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCICB, NCI, Ctr Bioinformat, Rockville, MD 20852 USA. Univ Manchester, Dept Comp Sci, Manchester M13 9PL, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stoeckert, CJ (reprint author), Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. EM Stoeckrt@pcbi.upenn.edu OI Parkinson, Helen/0000-0003-3035-4195; Sansone, Susanna-Assunta/0000-0001-5306-5690 FU NHGRI NIH HHS [1P41HG003619-01, P41HG003619] NR 21 TC 119 Z9 127 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2006 VL 22 IS 7 BP 866 EP 873 DI 10.1093/bioinformatics/btl005 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025FU UT WOS:000236251500014 PM 16428806 ER PT J AU Taylor, FB Lowe, K Thompson, C McFall, MM Peskind, ER Kanter, ED Allison, N Williams, J Martin, P Raskind, MA AF Taylor, FB Lowe, K Thompson, C McFall, MM Peskind, ER Kanter, ED Allison, N Williams, J Martin, P Raskind, MA TI Daytime prazosin reduces psychological distress to trauma specific cues in civilian trauma posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; PTSD; prazosin; emotional Stroop; norepinephrine; alpha-1 adrenoceptor ID CORTICOTROPIN-RELEASING-FACTOR; AMYGDALA; VETERANS; STIMULATION; NIGHTMARES; ACTIVATION; REDUCTION; RECEPTORS; SYMPTOMS; THREAT AB Background: Persons with posttraumatic stress disorder (PTSD) whose trauma-related nightmare improve or resolve with bedtime administration of the alpha-1 adrenergic antagonist prazosin often continue to experience PTSD symptoms during the day. This study addressed whether daytime prazosin compared to placebo would alleviate psychological distress provoked experimentally by a trauma-related word list included in the emotional Stroop (E-Strop) paradigm. Methods: Eleven persons with civilian trauma PTSD who continued to experience daytime PTSD symptoms despite a stable bedtime prazosin dose that suppressed trauma-related nightmares were studied. Prazosin and placebo were administered on two different occasions in the early afternoon followed two hours later by the E-Stroop. Effects of drug on psychological distress were assessed by the Profile of Mood States (POMS). Results: POMS total score and an "emotional distress" POMS subscale score following trauma-related words were significantly lower in the prazosin than placebo condition. There were no treatment effects on E-Stroop completion time. In 10 subjects who continued open label daytime prazosin; there was a reduction in global PTSD illness severity at 2-week follow-up. Conclusions: Daytime prazosin pretreatment reduced pyschological distress specifically to trauma cues. Adding daytime prazosin to bedtime prazosin may further reduce overall PTSD illness severity and distress. C1 Rainer Associates, Tacoma, WA 98467 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NW Network Vet Integrated Serv Network 20 Mental, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, Seattle, WA USA. RP Taylor, FB (reprint author), Rainer Associates, 5909 Orchard W, Tacoma, WA 98467 USA. EM tfletcher2@uswest.net FU NIMH NIH HHS [R01 MH069867] NR 27 TC 67 Z9 69 U1 1 U2 7 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 APR 1 PY 2006 VL 59 IS 7 BP 577 EP 581 DI 10.1016/j.biopsych.2005.09.023 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 026DA UT WOS:000236315700001 PM 16460691 ER PT J AU Woodward, SH Kaloupek, DG Streeter, CC Martinez, C Schaer, M Eliez, S AF Woodward, SH Kaloupek, DG Streeter, CC Martinez, C Schaer, M Eliez, S TI Decreased anterior cingulate volume in combat-related PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stress disorders; posttraumatic; magnetic resonance imaging; gyrus cinguli ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; FRONTAL MIDLINE THETA; SCRIPT-DRIVEN IMAGERY; POSITRON-EMISSION-TOMOGRAPHY; ERROR-RELATED-NEGATIVITY; CHILDHOOD SEXUAL-ABUSE; BRAIN ACTIVATION; DENDRITIC REORGANIZATION; FUNCTIONAL CONNECTIVITY AB Background: Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. Methods: Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size. Results: Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size. Conclusions: Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder. C1 VA Palo Alto HCS, Natl Ctr PTSD, Clin Lab & Educ Div, Palo Alto, CA 94034 USA. VA Palo Alto HCS, Natl Ctr PTSD, Psychol Serv, Palo Alto, CA 94034 USA. Boston Univ, Sch Med, Div Psychiat, Natl Ctr PTSD,VA Boston Healthcare Syst, Boston, MA 02118 USA. Boston Univ, Sch Med, Behav Sci Div, Boston, MA 02118 USA. Univ Geneva, Dept Psychiat, Geneva, Switzerland. RP Woodward, SH (reprint author), VA Palo Alto HCS, Natl Ctr PTSD, Clin Lab & Educ Div, Mail Code 334 PTSD,3801 Miranda Ave, Palo Alto, CA 94034 USA. EM steve.woodward@med.va.gov OI Kaloupek, Danny/0000-0002-0795-593X FU NIAAA NIH HHS [K23AA13149] NR 62 TC 136 Z9 142 U1 1 U2 12 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 APR 1 PY 2006 VL 59 IS 7 BP 582 EP 587 DI 10.1016/j.biopsych.2005.07.033 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 026DA UT WOS:000236315700002 PM 16165099 ER PT J AU Yehuda, R Brand, S Yang, RK AF Yehuda, R Brand, S Yang, RK TI Plasma neuropeptide y concentrations in combat exposed veterans: Relationship to trauma exposure, recovery from PTSD, and coping SO BIOLOGICAL PSYCHIATRY LA English DT Article DE coping; neuropeptide Y; neurotransmitters; posttraumatic stress disorder; resilience ID BASE-LINE; STRESS; NPY; DEPRESSION; INJECTION; CORTISOL; HORMONE; ANXIETY; BRAIN AB Background: There is emerging interest in examining the role of plasma neuropeptide Y (NPY) as a protective stress factor. Methods: To further investigate this possibility, plasma NPY was measured in 11 nonexposed veterans, 11 combat-exposed veterans without posttraumatic stress disorder (PTSD), and 12 veterans with current PTSD. Results: A significant group difference in plasma NPY (F-2.31=5.16, p=.012) was observed, reflecting higher NPY levels in exposed veterans without PTSD than in nonexposed but comparable levels in veterans with current PTSD. Among those without current PTSD, veterans with past PTSD bad higher NPY levels than Those without past PTSD (t(9)=2.71, p=.024). After controlling for all other variables, NPY levels were significantly predicted by extent of symptom improvement and lower combat exposure and significant at a trend level with positive coping. Conclusions: Plasma NPY levels may represent a biologic correlate of resilience to or recovery from the adverse effects of stress. C1 Mt Sinai Sch Med, Dept Psychiat, Traumat Stress Studies Program, New York, NY USA. Bronx Vet Affairs Med Ctr, New York, NY USA. RP Yehuda, R (reprint author), Bronx VA OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Rachel.Yehuda@med.va.gov FU NCRR NIH HHS [5 M01 RR00071] NR 23 TC 106 Z9 110 U1 3 U2 10 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 APR 1 PY 2006 VL 59 IS 7 BP 660 EP 663 DI 10.1016/j.biopsych.2005.08.027 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 026DA UT WOS:000236315700012 PM 16325152 ER PT J AU Couriel, D Carpenter, PA Cutler, C Bolanos-Meade, J Treister, NS Gea-Banacloche, J Shaughnessy, P Hymes, S Kim, S Wayne, AS Chien, JW Neumann, J Mitchell, S Syrjala, K Moravec, CK Abramovitz, L Liebermann, J Berger, A Gerber, L Schubert, M Filipovich, AH Weisdorf, D Schubert, MM Shulman, H Schultz, K Mittelman, B Pavletic, S Vogelsang, GB Martin, PJ Lee, SJ Flowers, MED AF Couriel, D Carpenter, PA Cutler, C Bolanos-Meade, J Treister, NS Gea-Banacloche, J Shaughnessy, P Hymes, S Kim, S Wayne, AS Chien, JW Neumann, J Mitchell, S Syrjala, K Moravec, CK Abramovitz, L Liebermann, J Berger, A Gerber, L Schubert, M Filipovich, AH Weisdorf, D Schubert, MM Shulman, H Schultz, K Mittelman, B Pavletic, S Vogelsang, GB Martin, PJ Lee, SJ Flowers, MED TI Ancillary therapy and supportive care of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic cell transplantation; supportive care; consensus ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; PNEUMOCOCCAL CONJUGATE VACCINE; SEVERE DRY EYE; PNEUMOCYSTIS-CARINII-PNEUMONIA; INTRAVENOUS IMMUNE GLOBULIN; ORAL LICHEN-PLANUS; TERM-FOLLOW-UP; DOUBLE-BLIND; TOPICAL TACROLIMUS AB The Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of "ancillary therapy and supportive care" embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach. (C) 2006 American Society, for Blood and Marrow Transplantation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. Univ Washington, Sch Med, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Texas Transplant Inst, San Antonio, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Minnesota, Minneapolis, MN USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Couriel, D (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dcouriel@mdanderson.org NR 146 TC 181 Z9 192 U1 2 U2 7 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2006 VL 12 IS 4 BP 375 EP 396 DI 10.1016/j.bbmt.2006.02.003 PG 22 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 028NL UT WOS:000236494600001 PM 16545722 ER PT J AU Bouley, R Hawthorn, G Russot, LM Lint, HY Ausiello, DA Brown, D AF Bouley, R Hawthorn, G Russot, LM Lint, HY Ausiello, DA Brown, D TI Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney epithelial cells: AQP2 is located in ' endocytosis-resistant ' membrane domains after vasopressin treatment SO BIOLOGY OF THE CELL LA English DT Article DE clathrin-coated pit; kidney collecting duct; LLC-PK1 cell; membrane protein trafficking; receptor down-regulation ID NEPHROGENIC DIABETES-INSIPIDUS; RENAL COLLECTING DUCT; PROTEIN-COUPLED RECEPTORS; WATER CHANNEL; APICAL MEMBRANE; PLASMA-MEMBRANE; RAT-KIDNEY; MEDIATED ENDOCYTOSIS; PRINCIPAL CELLS; FUNCTIONAL-ROLE AB Background information. Aquaporin 2 (AQP2) plays an important, VP (vasopressin)-regulated role in water reabsorption by the kidney. The amount of AQP2 expressed at the surface of principal cells results from an equilibrium between the AQP2 in intracellular vesicles and the AQP2 on the plasma membrane. VP shifts the equilibrium in favour of the plasma membrane and this allows osmotic equilibration to occur between the collecting duct lumen and the interstitial space. Membrane accumulation of AQP2 could result from a VP-induced increase in exocytosis, a decrease in endocytosis, or both. In the present study, we further investigated AQP2 accumulation at the cell surface, and compared it with V2R (VP type 2 receptor) trafficking using cells that express epitope-tagged AQP2 and V2R. Results. Endocytosis of V2R and of AQP2 are independent events that can be separated temporally and spatially. The burst of endocytosis seen after VP addition to target cells, when AQP2 accumulates at the cell surface, is primarily due to internalization of the V2R. Increased endocytosis is not induced by forskolin, which also induces membrane accumulation of AQP2 by direct stimulation of adenylate cyclase. This indicates that cAMP elevation is not the primary cause of the initial, VIP-incluced endocytic process. After VP exposure, AQP2 is not located in endosomes with internalized V2R. Instead, it remains at the cell surface in 'endocytosis-resistant' membrane domains, visualized by confocal imaging. After VP washout, AQP2 is progressively internalized with the fluid-phase marker FITC-dextran, indicating that VP washout releases an endocytotic block that maintains AQP2 at the cell surface. Finally, polarized application of VP to filter-grown cells shows that apical VIP can induce basolateral endocytosis and V2R down-regulation, and vice versa. Conclusions. After VP stimulation of renal epithelial cells, AQP2 accumulates at the cell surface, while the V2R is actively internalized. This endocytotic block may involve a reduced capacity of phosphorylated AQP2 to interact with components of the endocytotic machinery. In addition, a complex cross-talk exists between the apical and basolateral plasma-membrane domains with respect to endocytosis and V2R clown-regulation. This may be of physiological significance in down-regulating the VP response in the kidney in vivo. C1 Massachusetts Gen Hosp East, Program Membrane Biol, Boston, MA 02129 USA. Massachusetts Gen Hosp East, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp East, Program Membrane Biol, Boston, MA 02129 USA. EM brown@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK38452, DK43351, DK57521, DK19406] NR 78 TC 30 Z9 30 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD APR PY 2006 VL 98 IS 4 BP 215 EP 232 DI 10.1042/BC20040054 PG 18 WC Cell Biology SC Cell Biology GA 037YA UT WOS:000237182700002 PM 16563128 ER PT J AU Megeed, Z Winters, RM Yarmush, ML AF Megeed, Z Winters, RM Yarmush, ML TI Modulation of single-chain antibody affinity with temperature-responsive elastin-like polypeptide linkers SO BIOMACROMOLECULES LA English DT Article ID PROTEINS; DISSOCIATION; MINIDOMAIN; STABILITY; CORRELATE; SWITCHES; POLYMERS; BINDING; FORCES AB Single-chain antibodies are genetically engineered constructs composed of a V-H and V-L domain of an antibody linked by a flexible peptide linker, commonly (GGGGS)(3). We asked whether replacement of this flexible linker with peptides known to undergo environmentally induced structural transitions could lead to antibodies with controlled binding and release characteristics. To this end, we genetically modified and produced a series of anti-fluorescein single-chain antibodies with the general linker sequence (VPGXG)(n), where n is 1.2 to 3 and X is Val or His, to evaluate the effects of linker length and composition. Our results indicate that single-chain antibodies containing elastin-like polypeptide linkers have equilibrium affinity (K-D) comparable to wild-type (GGGGS)3 at room temperature but altered binding kinetics and faster ligand release as the temperature is raised. These results are consistent with the increased molecular order and contraction that elastin-like polypeptides are known to undergo with increased temperature. Modulation of antibody affinity using stimulus-responsive linkers may have applications in biosensors, drug delivery, and bioseparations. C1 Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, Massachusetts Gen Hosp, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIBIB NIH HHS [EB002503]; NIDDK NIH HHS [DK070496] NR 22 TC 25 Z9 25 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD APR PY 2006 VL 7 IS 4 BP 999 EP 1004 DI 10.1021/bm0507002 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 033SF UT WOS:000236868800001 PM 16602713 ER PT J AU Law, B Weissleder, R Tung, CH AF Law, B Weissleder, R Tung, CH TI Peptide-based biomaterials for protease-enhanced drug delivery SO BIOMACROMOLECULES LA English DT Article ID SELF-COMPLEMENTARY OLIGOPEPTIDE; BREAST-CANCER PATIENTS; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX; CYSTEINE PROTEASES; PROGNOSTIC IMPACT; UROKINASE; ANGIOGENESIS; INHIBITOR; INVASION AB Controlled delivery of drugs in response to environments has the potential of targeting therapies and personalized treatments. Here, we described self-assembled peptide sequences that release therapeutic payloads upon specific interaction with disease-associated proteases. The core peptide sequence consists of a protease cleavable region flanked by two self-assembly motifs. In aqueous solution, the peptides self-assemble as a gel scaffold. With treatment of the model preparations with the appropriate protease, the matrix can be degraded in a controlled fashion, where the degradation rate is fine-tuned by varying the peptide compositions. Protease-mediated drug release was demonstrated by enzymatic treatment of a model therapeutic peptide incorporated into the optimized matrix. Our results suggest that this type of material may have far-reaching applications for functionally targeted drug delivery. 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 38 TC 48 Z9 49 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1525-7797 J9 BIOMACROMOLECULES JI Biomacromolecules PD APR PY 2006 VL 7 IS 4 BP 1261 EP 1265 DI 10.1021/bm050920f PG 5 WC Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 033SF UT WOS:000236868800035 PM 16602747 ER PT J AU Oral, E Wannomae, KK Rowell, SL Muratoglu, OK AF Oral, E Wannomae, KK Rowell, SL Muratoglu, OK TI Migration stability of alpha-tocopherol in irradiated UHMWPE SO BIOMATERIALS LA English DT Article DE antioxidant; vitamin E; highly cross-linked polyethylene; joint replacement; degradation; oxidation ID MOLECULAR-WEIGHT POLYETHYLENE; VITAMIN-E; ANTIOXIDANT ACTIVITY; IN-VIVO; WEAR; RESISTANCE AB The oxidation resistance of irradiated ultra-high molecular weight polyethylene (UHMWPE) components used in total joint arthroplasty can be improved by adding alpha-tocopherol (vitamin E) through diffusion. To ensure long-term oxidative stability, a minimum alpha-tocopherol concentration needs to be maintained throughout these components. Migration of alpha-tocopherol out of the components is one mechanism that could compromise long-term oxidative stability. We hypothesized that alpha-tocopherol could elute out during standard implant fabrication steps such as cleaning as well as during in vivo use. We doped 85 kGy irradiated UHMWPE with alpha-tocopherol at 120 degrees C and homogenized at 120 degrees C. We determined the extent of elution of alpha-tocopherol or its effect on oxidative stability following cleaning in isopropyl alcohol (IPA) and following 5 million cycles (MC) of simulated normal gait in bovine serum. There was no significant elution of a-tocopherol in repeated and prolonged cleaning in IPA as measured by average surface and bulk a-tocopherol concentrations. There was no change in the oxidative stability following 5 MC of hip simulator testing, indicating minimal elution during simulated normal gait. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM orhun@alum.mit.edu FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-02, R01 AR051142-01] NR 19 TC 21 Z9 22 U1 0 U2 9 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 APR PY 2006 VL 27 IS 11 BP 2434 EP 2439 DI 10.1016/j.biomaterials.2005.11.001 PG 6 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 016PF UT WOS:000235631500012 PM 16325903 ER PT J AU Wang, ML Fitzmaurice, GM AF Wang, ML Fitzmaurice, GM TI A simple imputation method for longitudinal studies with non-ignorable non-responses SO BIOMETRICAL JOURNAL LA English DT Article DE generalized estimating equations; imputation; longitudinal data; missing data; non-ignorable ID PATTERN-MIXTURE-MODELS; LOGISTIC-REGRESSION MODELS; DROP-OUT; BINARY RESPONSES; MISSING DATA; SEMIPARAMETRIC REGRESSION; NONIGNORABLE NONRESPONSE; REPEATED OUTCOMES; INCOMPLETE DATA AB Missing data are a common problem in longitudinal studies in the health sciences. Motivated by data from the Muscatine Coronary Risk Factor (MCRF) study, a longitudinal study of obesity, we propose a simple imputation method for handling non-ignorable non-responses (i.e., when non-response is related to the specific values that should have been obtained) in longitudinal studies with either discrete or continuous outcomes. In the proposed approach, two regression models are specified; one for the marginal mean of the response, the other for the conditional mean of the response given non-response patterns. Statistical inference for the model parameters is based on the generalized estimating equations (GEE) approach. An appealing feature of the proposed method is that it can be readily implemented using existing, widely-available statistical software. The method is illustrated using longitudinal data on obesity from the MCRF study. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02120 USA. RP Wang, ML (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM mwang@jimmy.harvard.edu FU NIGMS NIH HHS [GM 29745] NR 27 TC 14 Z9 14 U1 1 U2 5 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD APR PY 2006 VL 48 IS 2 BP 302 EP 318 DI 10.1002/bimj.200510188 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 039PE UT WOS:000237317900009 PM 16708780 ER PT J AU Glahn, DC Bearden, CE Cakir, S Barrett, JA Najt, P Monkul, ES Maples, N Velligan, DI Soares, JC AF Glahn, DC Bearden, CE Cakir, S Barrett, JA Najt, P Monkul, ES Maples, N Velligan, DI Soares, JC TI Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; delayed response task; digit span; psychotic features; schizoaffective disorder; schizophrenia; working memory ID 1ST-DEGREE RELATIVES; RATING-SCALE; FAMILY; DYSFUNCTION; SYMPTOMS; SUSCEPTIBILITY; ASSOCIATION; PERFORMANCE; PEDIGREES; REMISSION AB Background: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. Method: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. Results: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. Conclusions: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Schizophrenia & Related Disorders, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. RP Glahn, DC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Schizophrenia & Related Disorders, Mail Code 7792,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM glahn@uhscsa.edu FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH 01736, MH 068662] NR 44 TC 109 Z9 112 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2006 VL 8 IS 2 BP 117 EP 123 DI 10.1111/j.1399-5618.2006.00296.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 021YS UT WOS:000236022400002 PM 16542181 ER PT J AU Faraone, SV Lasky-Su, J Glatt, SJ Eerdewegh, PV Tsuang, MT AF Faraone, SV Lasky-Su, J Glatt, SJ Eerdewegh, PV Tsuang, MT TI Early onset bipolar disorder: possible linkage to chromosome 9q34 SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; chromosome 9; early onset; linkage analysis; ordered subsets analysis ID OLD-ORDER AMISH; GENOME-WIDE SEARCH; FAMILIAL TRANSMISSION; DIAGNOSTIC INTERVIEW; SUSCEPTIBILITY LOCI; SCAN; PEDIGREES; ILLNESS; SCHIZOPHRENIA; METAANALYSIS AB Objectives: Bipolar disorder (BD) is characterized by manic and depressive states that onset at various times in life. Research shows that early onset forms of BD are associated with a stronger genetic loading for the illness. We hypothesized that using age at onset to look at subsets of BD families in a genetic linkage analysis would prove useful in separating etiologically homogeneous BD sub-groups and subsequently identifying genetic susceptibility regions. Methods: We used the wave-I National Institute of Mental Health (NIMH) Genetics Initiative BD sample, which includes 540 individuals from 97 families with BD, in an ordered-subsets linkage analysis with age at onset of mania as the subset-identifying covariate. This analysis was performed using GENEHUNTER-PLUS followed by the ordered-subsets analysis program. This program generates empirical p-values for the subset with the largest LOD score to determine whether this value was significantly higher than the baseline LOD score using all families. Results: Three chromosomal regions resulted in LOD scores above 2.0: 2.21 (6q25), 3.21 (9q34), and 2.16 (20q11). The largest increase in LOD score was observed on chromosome 9q34 between markers D9S290 and D9S915 in the subset of 58 families that had mania onset before age 20. Families with a minimal mania onset less than 20 years had a significantly greater number of psychiatric comorbidities (p = 0.02) and a marginal increase in depressive symptoms (p = 0.10). Conclusions: Further investigation into chromosomal region 9q34 is necessary to determine whether this region may harbor a gene specific to families with a minimal age at onset of less than 20. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Univ Calif San Diego, Inst Behav Genom, San Diego, CA 92103 USA. Galileo Genom, Montreal, PQ, Canada. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R13MH59126, R01MH57934] NR 43 TC 29 Z9 29 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2006 VL 8 IS 2 BP 144 EP 151 DI 10.1111/j.1399-5618.2006.00289.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 021YS UT WOS:000236022400005 PM 16542184 ER PT J AU Evins, AE Demopulos, C Yovel, I Culhane, M Ogutha, J Grandin, LD Nierenberg, AA Sachs, GS AF Evins, AE Demopulos, C Yovel, I Culhane, M Ogutha, J Grandin, LD Nierenberg, AA Sachs, GS TI Inositol augmentation of lithium or valproate for bipolar depression SO BIPOLAR DISORDERS LA English DT Article; Proceedings Paper CT 5th International Conference on Bipolar Disorder CY JUN 12-14, 2003 CL Pittsburgh, PA DE affective disorder; bipolar disorder; depression; inositol; lithium; second messenger; valproate ID DOUBLE-BLIND; RATING-SCALE; CROSSOVER TRIAL; PANIC DISORDER; UNITED-STATES; CSF INOSITOL; MANIA; CLOZAPINE; VALIDATION; DULOXETINE AB Objective: Despite promising new therapies, bipolar depression remains difficult to treat. Up to half of patients do not respond adequately to currently approved treatments. This study evaluated the efficacy of adjunctive inositol for bipolar depression. Methods: Seventeen participants with DSM-IV criteria for bipolar depression and a 17-item Hamilton Rating Scale for Depression (HRSD) >= 15 on proven therapeutic levels of lithium or valproate for > 2 weeks were randomized to receive double-blind inositol or placebo for 6 weeks. At the end of double-blind treatment, subjects were eligible for an 8-week open-label trial of inositol. Results: Response was defined a priori as > 50% reduction in the HRSD and a Clinical Global Impression of 1-2. Four of nine subjects (44%) on inositol and zero of eight subjects on placebo met response criteria (p = 0.053). There was no difference between groups in the average change score for the HRSD or Young Mania Rating Scale (YMRS). Response to inositol was highly variable. Of nine subjects randomized to inositol, two had > 50% worsening in HRSD scores at the end of treatment, three had no change and four had > 50% improvement. Those who had worsening in depressive symptoms on inositol had significantly higher scores at baseline on the YMRS total score and irritability, disruptive/aggressive behavior and unkempt appearance items. Conclusions: There was a trend for more subjects on inositol to show improvement in bipolar depression symptoms, but, on average, inositol was not more effective than placebo as an adjunct for bipolar depression. Baseline levels of anger or hostility may be predictive of clinical response to inositol. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Bipolar Res Program, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, 25 Staniford St, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 33 TC 35 Z9 35 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2006 VL 8 IS 2 BP 168 EP 174 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 021YS UT WOS:000236022400008 ER PT J AU Sachs, G Bowden, C Calabrese, JR Ketter, T Thompson, T White, R Bentley, B AF Sachs, G Bowden, C Calabrese, JR Ketter, T Thompson, T White, R Bentley, B TI Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; lamotrigine; lithium; maintenance therapy; weight ID CONTROLLED 18-MONTH TRIAL; CORONARY-HEART-DISEASE; RISK; GAIN; OBESITY AB Objective: The effect of lamotrigine maintenance therapy on body weight was assessed retrospectively in analyses of data from two double-blind, placebo- and lithium-controlled, 18-month studies in patients with bipolar I disorder (n = 227 for lamotrigine, 190 for placebo, 166 for lithium). Methods: Endpoints included mean change in weight, the percentage of patients with >= 7% change (increase, decrease, fluctuation) in weight, and the percentage of patients with weight-related adverse events during double-blind treatment. Results: Mean weight remained stable during maintenance therapy with lamotrigine. In a mixed-model repeated-measures analysis, mean changes in weight (kg) at week 52 were -1.2 with lamotrigine, +0.2 with placebo, and +2.2 with lithium [estimated difference (95% CI) lamotrigine minus placebo = -1.3 (-3.6, 0.9), p = 0.237; lithium minus placebo = +2.0 (-0.3, 4.4), p = 0.094; lithium minus lamotrigine = +3.4 (1.4, 5.4), p < 0.001]. Analyses were truncated at week 52 because of the high incidence of missing data at later time points. The percentages of patients with a >= 7% weight gain, during randomized treatment, were 10.9%, 7.6% and 11.8% for the lamotrigine, placebo, and lithium groups, respectively. The percentages of patients with a >= 7% weight loss, during randomized treatment, were 12.1%, 11.5%, and 5.1% for the lamotrigine, placebo, and lithium groups, respectively. The percentage of patients with a >= 7% weight loss did not significantly differ between lamotrigine and placebo but was significantly higher with lamotrigine than lithium. The incidences of >= 7% weight changes and of weight changes reported as adverse events were comparable between active treatments and placebo. Conclusion: Lamotrigine was associated with stable body weight during 1 year of treatment and was comparable to placebo in mean weight change, incidence of clinically significant weight change, and incidence of weight changes reported as adverse events in patients with bipolar disorder. Lithium was associated with weight gain, but the magnitude of lithium-associated weight gain was lower in the current analysis than in previous studies. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Sachs, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. EM sachsg@aol.com NR 12 TC 40 Z9 40 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2006 VL 8 IS 2 BP 175 EP 181 DI 10.1111/j.1399-5618.2006.00308.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 021YS UT WOS:000236022400009 PM 16542188 ER PT J AU Nakabayashi, M Oh, WK AF Nakabayashi, M Oh, WK TI Chemotherapy for high-risk localized prostate cancer SO BJU INTERNATIONAL LA English DT Review DE high-risk localized prostate cancer; chemotherapy; neoadjuvant; adjuvant ID PHASE-II TRIAL; RADICAL PROSTATECTOMY; NEOADJUVANT DOCETAXEL; RADIATION-THERAPY; ADJUVANT THERAPY; BREAST-CANCER; ESTRAMUSTINE; MITOXANTRONE; RECEPTOR; SURGERY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lank Ctr Genitourinary Oncol, 44 Binney St,D1230, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 34 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2006 VL 97 IS 4 BP 679 EP 683 DI 10.1111/j.1464-410X.2006.06092.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 020EO UT WOS:000235891400006 PM 16536752 ER PT J AU Lensch, MW Daley, GQ AF Lensch, MW Daley, GQ TI Scientific and clinical opportunities for modeling blood disorders with embryonic stem cells SO BLOOD LA English DT Review ID BONE-MARROW-TRANSPLANTATION; DIFFERENTIATION IN-VITRO; DOWN-SYNDROME PHENOTYPES; JAN 20 2006; FANCONI-ANEMIA; HEMATOPOIETIC-CELLS; MAMMALIAN-CELLS; MOUSE EMBRYOS; YOLK-SAC; MYELOPROLIFERATIVE DISORDER AB Our considerable wealth of data concerning hematologic processes has come despite difficulties working with stem and progenitor cells in vitro and their propensity to differentiate. Key methodologies that have sought to overcome such limitations include transgenic/knock-out animals and in vitro studies using murine embryonic stem cells, because both permit investigation of the formation of hematopoletic tissue from nonhematopoietic precursors. Although there have been many successful studies in model animals for understanding hematopoietic-cell development, differences between lower vertebrates and humans have left gaps in our understanding. Clearly, human-specific strategies to study the onset of hematopoiesis, particularly the earliest events leading to the specification of both normal and abnormal hematopoietic tissue, could bring an investigational renaissance. The recent availability of human embryonic stem (hES) cells suggests that such a system is now at hand. This review highlights the potential of hES cells to model human hematologic processes in vitro with an emphasis on disease targets. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu NR 128 TC 26 Z9 27 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 APR 1 PY 2006 VL 107 IS 7 BP 2605 EP 2612 DI 10.1182/blood-2005-07-2991 PG 8 WC Hematology SC Hematology GA 030TG UT WOS:000236656900013 PM 16332966 ER PT J AU Bennett, CM Rogers, ZR Kinnamon, DD Bussel, JB Mahoney, DH Abshire, TC Sawaf, H Moore, TB Loh, ML Glader, BE McCarthy, MC Mueller, BU Olson, TA Lorenzana, AN Mentzer, WC Buchanan, GR Feldman, HA Neufeld, EJ AF Bennett, CM Rogers, ZR Kinnamon, DD Bussel, JB Mahoney, DH Abshire, TC Sawaf, H Moore, TB Loh, ML Glader, BE McCarthy, MC Mueller, BU Olson, TA Lorenzana, AN Mentzer, WC Buchanan, GR Feldman, HA Neufeld, EJ CA Pediat Rituximab ITP Grp Glaser Pediat Res Network TI Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura SO BLOOD LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-of-Pediatric-Hematology-Oncology CY MAY 13-17, 2005 CL Washington, DC SP Amer Soc Pediat Hematol & Oncol ID ANTI-CD20 MONOCLONAL-ANTIBODY; B-CELL DEPLETION; LYMPHOMA; CHILDREN; ADULTS; IDEC-C2B8; THERAPY AB We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 x 10(9)/L (50 000/ mm(3)) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [Cl], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included thirddose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Clin Res Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Cornell Univ, Weill Med Coll, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Emory Univ, Sch Med, Atlanta, GA USA. St Johns Hosp, Van Eslander Canc Ctr, Detroit, MI USA. Univ Calif Los Angeles, Mattel Childrens Hosp, San Francisco, CA USA. Stanford Univ, Stanford, CA 94305 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011; Kinnamon, Daniel/J-4207-2013 FU NCRR NIH HHS [M01-RR-01271, M01-RR000047, M01RR000188, M01RR00865, M01RR02172] NR 19 TC 133 Z9 140 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2006 VL 107 IS 7 BP 2639 EP 2642 DI 10.1182/blood-2005-08-3518 PG 4 WC Hematology SC Hematology GA 030TG UT WOS:000236656900019 PM 16352811 ER PT J AU Duda, DG Cohen, KS Kozin, SV Perentes, JY Fukumura, D Scadden, DT Jain, RK AF Duda, DG Cohen, KS Kozin, SV Perentes, JY Fukumura, D Scadden, DT Jain, RK TI Evidence for incorporation of bone marrow-derived endothelial cells into perfused blood vessels in tumors SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PROGENITOR CELLS; ANGIOGENESIS; CONTRIBUTE; GROWTH; NEOVASCULARIZATION; PRECURSORS AB Recent studies have demonstrated that the cellular contribution of the bone marrow to tumor neovascularization is highly complex. In this context, the extent to which bone marrow-derived cells incorporate as bona fide endothelial (nonhematopoietic) cells into perfused tumor vessels, or any new vessels formed postnatally (vasculogenesis), is unclear. To this end, we developed models to characterize local vessel-derived and bone marrow-derived endothelial cells (BMD-ECs). Then, we characterized the BMD-ECs based on a set of endothelial markers and morphology. Finally, we quantified their contribution to perfused blood vessels in tumors using transplanted as well as spontaneous primary and metastatic tumor models. We demonstrate that BMD-ECs incorporate in perfused tumor vessels, and that this contribution varies with organ site and mouse strain. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Univ Lausanne Hosp, Dept Thorac Surg, Lausanne, Switzerland. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, COX 734,100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [P01-CA80124, R01-CA115767, R01-CA96915] NR 24 TC 102 Z9 106 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2006 VL 107 IS 7 BP 2774 EP 2776 DI 10.1182/blood-2005-08-321 PG 3 WC Hematology SC Hematology GA 030TG UT WOS:000236656900037 PM 16339405 ER PT J AU von Bergwelt-Baildon, M Shimabukuro-Vornhagen, A Popov, A Klein-Gonzalez, N Fiore, F Debey, S Draube, A Maecker, B Menezes, I Nadler, LM Schultze, JL AF von Bergwelt-Baildon, M Shimabukuro-Vornhagen, A Popov, A Klein-Gonzalez, N Fiore, F Debey, S Draube, A Maecker, B Menezes, I Nadler, LM Schultze, JL TI CD40-activated B cells express full lymph node homing triad and induce T-cell chemotaxis: potential as cellular adjuvants SO BLOOD LA English DT Article ID ANTIGEN-PRESENTING CELLS; CHEMOKINE RECEPTOR EXPRESSION; HUMAN DENDRITIC CELLS; TUMOR-ANTIGENS; ORGANS; MATURATION; MIGRATION; RESPONSES; IMMUNOTHERAPY; TRAFFICKING AB CD40-activated B cells (CD40-B cells) have previously been introduced as an alternative source of antigen-presenting cells for immunotherapy. CD40-B cells can prime naive and expand memory T cells, and they can be generated in large numbers from very small amounts of peripheral blood derived from healthy individuals or cancer patients alike. Administration of CD40-B cells as a cellular adjuvant would require these cells to migrate toward secondary lymphoid organs and attract T cells in situ, processes guided by specific chemokines and chemokine receptors. Here, we demonstrate that primary, human CD40-B cells express a pattern of adhesion molecules and chemokine receptors necessary for homing to secondary lymphoid organs and have the capacity to migrate to cognate ligands. Furthermore, we show that CD40-B cells express important T-cell attractants and induce strong T-cell chemotaxis. These findings further support the use of CD40-B cells as cellular adjuvant for cancer immunotherapy. C1 Univ Cologne, Clin Internal Med Hematol & Oncol 1, D-50924 Cologne, Germany. Univ Cologne, Ctr Mol Med, D-50924 Cologne, Germany. Univ Turin, Div Ematol, I-10124 Turin, Italy. Osped San Giovanni Battista Torino, Ctr Ricerca Med Sperimentale, Lab Ematol Oncol, I-10124 Turin, Italy. Hannover Med Sch, D-3000 Hannover, Germany. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Univ Cologne, Clin Internal Med Hematol & Oncol 1, Kerpener Str 62, D-50924 Cologne, Germany. EM joachim.schultze@medizin.uni-koeln.de RI Schultze, Joachim/D-7794-2011; OI Schultze, Joachim/0000-0003-2812-9853; Shimabukuro-Vornhagen, Alexander/0000-0002-2351-7294 FU NCI NIH HHS [P01-CA-66996, P01-CA-78378] NR 30 TC 36 Z9 36 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 APR 1 PY 2006 VL 107 IS 7 BP 2786 EP 2789 DI 10.1182/blood-2004-01-0113 PG 4 WC Hematology SC Hematology GA 030TG UT WOS:000236656900039 PM 16357329 ER PT J AU Viatte, L Nicolas, G Lou, DQ Bennoun, M Lesbordes-Brion, JC Canonne-Hergaux, F Schonig, K Bujard, H Kahn, A Andrews, NC Vaulont, S AF Viatte, L Nicolas, G Lou, DQ Bennoun, M Lesbordes-Brion, JC Canonne-Hergaux, F Schonig, K Bujard, H Kahn, A Andrews, NC Vaulont, S TI Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice SO BLOOD LA English DT Article ID ANTIMICROBIAL PEPTIDE HEPCIDIN; FERROPORTIN DISEASE; JUVENILE HEMOCHROMATOSIS; TRANSGENIC MICE; GENE-EXPRESSION; LIVER HEPCIDIN; MOUSE MODEL; OVERLOAD; ANEMIA; HOMEOSTASIS AB We report the generation of a tetracycline-regulated (Tet ON) transgenic mouse model for acute and chronic expression of the iron regulatory peptide hepcidin in the liver. We demonstrate that short-term and long-term tetracycline-dependent activation of hepcidin in adult mice leads to hypoferremia and iron-limited erythropoiesis, respectively. This clearly establishes the key role of hepcidin in regulating the extracellular iron concentration. We previously demonstrated that, when expressed early in fetal development, constitutive transgenic hepcidin expression prevented iron accumulation in an Hfe(-/-) mouse model of hemochromatosis. We now explore the effect of chronic hepcidin expression in adult Hfe(-/-) mice that have already developed liver iron overload. We demonstrate that induction of chronic hepcidin expression in 2-month-old Hfe(-/-) mice alters their pattern of cellular iron accumulation, leading to increased iron in tissue macrophages and duodenal cells but less iron in hepatocytes. These hepcidin-induced changes in the pattern of cellular iron accumulation are associated with decreased expression of the iron exporter ferroportin in macrophages but no detectable alteration of ferroportin expression in the hepatocytes. We speculate that this change in iron homeostasis could offer a therapeutic advantage by protecting against damage to parenchymal cells. C1 Fac Med Cochin, Inst Cochin, Dept Genet Dev & Pathol Mol, F-75014 Paris, France. Univ Paris Descartes, CNRS, UMR 8104, INSERM,U567,UMR S 8104, Paris, France. INSERM, U656, Inst Natl Transfus Sanguine, Paris, France. Univ Paris 07, INSERM, U409, Paris, France. Zentrum Mol Biol, D-6900 Heidelberg, Germany. Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Vaulont, S (reprint author), Fac Med Cochin, Inst Cochin, Dept Genet Dev & Pathol Mol, 24 Rue Faubourg St Jacques, F-75014 Paris, France. EM vaulont@cochin.inserm.fr RI NICOLAS, Gael/D-7611-2013; OI NICOLAS, Gael/0000-0002-1671-8274; Andrews, Nancy/0000-0003-0243-4462 NR 41 TC 53 Z9 57 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 APR 1 PY 2006 VL 107 IS 7 BP 2952 EP 2958 DI 10.1182/blood-2005-10-4071 PG 7 WC Hematology SC Hematology GA 030TG UT WOS:000236656900061 PM 16339398 ER PT J AU Yang, DH Guo, J Divieti, P Bringhurst, FR AF Yang, DH Guo, J Divieti, P Bringhurst, FR TI Parathyroid hormone activates PKC-delta and regulates osteoblastic differentiation via a PLC-independent pathway SO BONE LA English DT Article DE parathyroid hormone; parathyroid hormone receptor; protein kinase C; osteoblastic differentiation ID PROTEIN-KINASE-C; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; STIMULATED BONE-RESORPTION; PTH/PTHRP RECEPTOR; PHOSPHATE-TRANSPORT; CELL-PROLIFERATION; SIGNALING PATHWAYS; PHOSPHOLIPASE-C; GENE-EXPRESSION; CYCLIC-AMP AB PTH exerts major effects upon bone by activating PTH/PTHrP receptors (PTH1Rs) expressed on osteoblasts. The PTH1R is capable of engaging multiple signaling pathways in parallel, including Gs/adenylyl cyclase (AC), Gq/phospholipase C/protein kinase C (PLC/PKC) and a distinct mechanism, involving activation of PKC via a PLC-independent pathway, that depends upon ligand determinants within the PTH(2934) sequence. The involvement of PLC-dependent vs. PI-C-independent PKC activation in PTH action was Studied in clonal PTH1R-expressing murine calvarial osteoblasts ("Wt9") using two signal-selective analogs, [G(1),R-19]hPTH(1-28) and [G(1),R-19]hPTH(1-34). Both analogs lack PLC signaling but differ in their capacity to activate the PI-C-independent PKC pathway. Both hPTH(1-34) and [G(1),R-19]hPTH (1-34), but not [G(1),R-19]hPTH(1-28), increased differentiation of Wt9 cells during a 16-day alternate-daily treatment protocol. Wt9 cells expressed PKC-beta 1, -delta, -epsilon and -zeta none of which exhibited net translocation to membranes in response to hPTH(1-34) or either analog. hPTH (1-34) induced activation of membrane-associated PKC-delta, however, and a time- and concentration-dependent increase in cytosolic [phosphoThr(505)]PKC-delta which was maximal within 40 s at 100 nM in both Wt9 cells and primary osteoblasts. This response was mimicked by [G(1),R-19] hPTH(1-34) but not by [G(1),R-19]hPTH(1-28). Increased expression of bone sialoprotein (BSP) and osteocalcin (OC) mRNAs induced by PTH (1-34) and [G(1),R-19]hPTH(1-34) in Wt9 cells was blocked by rottlerin, a PKC-delta inhibitor. We conclude that PTH1Rs activate PKC-delta by a PLC-independent, PTH(29-34)-dependent mechanism that promotes osteoblastic differentiation. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM rbringhurst@partners.org FU NIDDK NIH HHS [DK65032, DK11794, DK02889] NR 52 TC 29 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2006 VL 38 IS 4 BP 485 EP 496 DI 10.1016/j.bone.2005.10.009 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 030VX UT WOS:000236664300003 PM 16325485 ER PT J AU Weinand, C Pomerantseva, I Neville, CM Gupta, R Weinberg, E Madisch, I Shapiro, F Abukawa, H Troulis, MJ Vacanti, JP AF Weinand, C Pomerantseva, I Neville, CM Gupta, R Weinberg, E Madisch, I Shapiro, F Abukawa, H Troulis, MJ Vacanti, JP TI Hydrogel-beta-TCP scaffolds and stem cells for tissue engineering bone SO BONE LA English DT Article DE mesenchymal stem cells; bone tissue engineering; three-dimensional printing; beta-TCP scaffolds; hydrogels; volumetric CT scanning ID MARROW STROMAL CELLS; IN-VITRO; ALGINATE HYDROGELS; DIFFUSION-CHAMBERS; DIFFERENTIATION; CARTILAGE; REPAIR; VIVO; RECONSTRUCTION; REGENERATION AB Trabecular bone is a material of choice for reconstruction after trauma and tumor resection and for correction of congenital defects. Autologous bone grafts are available in limited shapes and sizes; significant donor site morbidity is another major disadvantage to this approach. To overcome these limitations, we used a tissue engineering approach to create bone replacements in vitro, combining bone-marrow-derived differentiated mesenchymal stem cells (MSCs) suspended in hydrogels and 3-dimensionally printed (3DP) porous scaffolds made of beta-tricalcium-phosphate (beta-TCP). The scaffolds provided support for the formation of bone tissue in collagen 1, fibrin, alginate, and pluronic F127 hydrogels during culturing in oscillating and rotating dynamic conditions. Histological evaluation including toluidine blue, alkaline phosphatase, and von Kossa staining was done at 1, 2, 4, and 6 weeks. Radiographic evaluation and high-resolution volumetric CT (VCT) scanning, expression of bone-specific genes and biomechanical compression testing were performed at 6 weeks. Both culture conditions resulted in similar bone tissue formation. Histologically collagen I and fibrin hydrogels specimens had superior bone tissue, although radiopacities were detected only in collagen I samples. VCT scan revealed density values in all but the Pluronic F127 samples, with Houndsfield unit values comparable to native bone in collagen I and fibrin glue samples. Expression of bone-specific genes was significantly higher in the collagen I samples. Pluronic F127 hydrogel did not support formation of bone tissue. All samples cultured in dynamic oscillating conditions had slightly higher mechanical strength than under rotating conditions. Bone tissue can be successfully formed in vitro using constructs comprised of collagen I hydrogel, MSCs, and porous beta-TCP scaffolds. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pediat Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Childrens Hosp,Orthoped Res Lab, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp,Orthoped Res Lab, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent, Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Pediat Surg, Lab Tissue Engn & Organ Fabricat, Warren 11-1157,55 Fruit St, Boston, MA 02114 USA. EM JVacanti@Partners.Org NR 40 TC 101 Z9 116 U1 2 U2 57 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2006 VL 38 IS 4 BP 555 EP 563 DI 10.1016/j.bone.2005.10.016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 030VX UT WOS:000236664300010 PM 16376162 ER PT J AU Tholouli, E Di Vizio, D O'Connell, F Macdermott, SA Twomey, D Levenson, R Hoyland, JA Yin, JAL Golub, TR Loda, M Byers, RJ AF Tholouli, E Di Vizio, D O'Connell, F Macdermott, SA Twomey, D Levenson, R Hoyland, JA Yin, JAL Golub, TR Loda, M Byers, RJ TI In situ gene expression profiling and quantitation using quantum dot based multiplex hybridisation in clinical samples SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 46th Annual Scientific Meetign of the British-Society-for-Haematology CY APR 03-05, 2006 CL Edinburgh, ENGLAND SP British Soc Haematol C1 Manchester Royal Infirm, Univ Dept Haematol, Manchester M13 9WL, Lancs, England. Dana Farber Canc Ctr Inst, Dept Pathol, Boston, MA USA. Univ Manchester, Div Lab & Regenrat Med, Manchester, Lancs, England. Broad Inst MIT & Harvard, Boston, MA USA. Cambridge Res Instruments Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2006 VL 133 SU 1 BP 26 EP 26 PG 1 WC Hematology SC Hematology GA 026GD UT WOS:000236326500065 ER PT J AU Crawford, L Ovaa, H Walker, B Chauhan, D Anderson, KC Morris, TCM Irvine, AE AF Crawford, L Ovaa, H Walker, B Chauhan, D Anderson, KC Morris, TCM Irvine, AE TI Comparative specificity of the proteasome inhibitors BzLLLCOCHO, PS-341 and MG-132 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 46th Annual Scientific Meetign of the British-Society-for-Haematology CY APR 03-05, 2006 CL Edinburgh, ENGLAND SP British Soc Haematol C1 Belfast City Hosp, CCRCB, Belfast, Antrim, North Ireland. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Queens Univ Belfast, Dept Pharm, Belfast, Antrim, North Ireland. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Belfast City Hosp, Dept Haematol, Belfast, Antrim, North Ireland. RI IRVINE, ALEXANDRA/B-3497-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2006 VL 133 SU 1 BP 30 EP 30 PG 1 WC Hematology SC Hematology GA 026GD UT WOS:000236326500073 ER PT J AU Zacharia, TT O'Neill, MJ AF Zacharia, TT O'Neill, MJ TI Prevalence and distribution of adnexal findings suggesting endometriosis in patients with MR diagnosis of adenomyosis SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article; Proceedings Paper CT 104th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 02-07, 2004 CL Miami Beach, FL SP Amer Roentgen Ray Soc ID PELVIC ENDOMETRIOSIS; ULTRASONOGRAPHY; WOMEN AB The purpose of this investigation was to establish the prevalence and distribution of MR findings associated with pelvic endometriosis in patients with a MRI diagnosis of adenomyosis. Retrospective review of the pelvic MRI in 59 patients (age 32-54 years, mean 42 years) who met strict MRI criteria for adenomyosis was performed. T-1 weighted fat saturated and T-2 weighted images in these patients were reviewed for the presence or absence of T-1 bright signal suggesting endometriosis in any of nine locations (uterine serosa, right and left ovary, right and left fallopian tube, right and left broad ligament, and right and left pelvic side wall). 20 (20/59) patients (34%), showed characteristic MRI features associated with endometriosis. A total of 54 sites of involvement were identified (uterine serosa n=17, ovaries n=14, broad ligaments n=10, fallopian tubes n=8, pelvic side walls n=5) in 20 patients with an average of 2.7 sites per patient. implants (n=43) were more common than endometriomas (n=11). Endometriomas occurred most often in the ovaries (ovaries n=9, broad ligament n=2) whereas implants were seen on all locations (uterine serosa n=17, ovaries n=5, broad ligaments n=8, fallopian tubes n=8, pelvic side walls n=5). One third of patients with adenomyosis diagnosed by MRI also had MRI findings of endometriosis, with serosal implants being the most common finding. Imaging protocols should routinely include T-1 weighted fat saturated imaging sequences in order to detect coexistent endometriosis in patents undergoing pelvic MRI for the diagnosis of adenomyosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Zacharia, TT (reprint author), 4225 Elmhurst Ave,Ithaca St,Queens, New York, NY 11373 USA. OI Zacharia, Thomas/0000-0002-6908-9440 NR 16 TC 11 Z9 12 U1 0 U2 2 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD APR PY 2006 VL 79 IS 940 BP 303 EP 307 DI 10.1259/bjr/70121266 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XR UT WOS:000236669200006 PM 16585722 ER PT J AU Punglia, RS D'Amico, AV Catalona, WJ Roehl, KA Kuntz, KM AF Punglia, RS D'Amico, AV Catalona, WJ Roehl, KA Kuntz, KM TI Impact of age, benign prostatic hyperplasia, and cancer on prostate-specific antigen level SO CANCER LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 2005 CL Orlando, FL SP Amer Soc Clin Oncol DE prostate-specific antigen; mass screening; bias (epidemiology); prostatic neoplasms ID PSA CUTOFFS; MEN; VERIFICATION; BIAS AB BACKGROUND. The distribution of prostate-specific antigen (PSA) values for men with or without prostate carcinoma are confounded because of verification Was. Correcting for verification bias, the means and variances of PSA values were estimated in specific clinical scenarios. METHODS. Existing receiver operating characteristic (ROC) curves, adjusted for the presence of verification Was in a screening population, were used to estimate the mean an(] variance of PSA values for men with or without prostate carcinoma, stratified by age and the presence or absence of benign prostatic hyperplasia. Men with a Suspicious digital rectal exam (nodular) were excluded from analysis. RESULTS. Among men with cancer and the absence of benign prostatic hyperplasia, mean PSA values were 2.05 ng/mL and 2.66 ng/ml, for younger (< 60 yr) and older (>= 60 yrs) men, respectively. These estimates were 2.56 ng/mL and 3.90 ng/mL., in the presence of benign prostatic hyperplasia for Younger and older men, respectively. I-or men without prostate carcinoma, these values were 0.78 ng/mL and 1.23 ng/mL for Younger and older men, respectively, among those without benign prostatic hyperplasia, and 0.97 ng/mL and 1.75 ng/mL for Younger and older men, respectively, among those with benign prostatic hyperplasia. CONCLUSIONS. Accurate estimates of the mean and variance of PSA values for men with or without cancer may provide PSA thresholds for biopsy that are specific for age and prostate size as assessed by digital rectal exam. Therefore, the current threshold of 4.0 ng/mL Should not be applied indiscriminately. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. Northwestern Univ, Fineberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Kuntz, KM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, 718 Huntington Ave, Boston, MA 02115 USA. EM kmk@hsph.harvard.edu NR 9 TC 22 Z9 24 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2006 VL 106 IS 7 BP 1507 EP 1513 DI 10.1002/cncr.21766 PG 7 WC Oncology SC Oncology GA 024KI UT WOS:000236193500011 PM 16518812 ER PT J AU Carrasco, DR Tonon, G Huang, YS Zhang, YY Sinha, R Bin, F Stewart, JP Zhan, FG Khatry, D Protopopova, M Protopopov, A Sukhdeo, K Hanamura, I Stephens, O Barlogie, B Anderson, KC Chin, L Shaughnessy, JD Brennan, C DePinho, RA AF Carrasco, DR Tonon, G Huang, YS Zhang, YY Sinha, R Bin, F Stewart, JP Zhan, FG Khatry, D Protopopova, M Protopopov, A Sukhdeo, K Hanamura, I Stephens, O Barlogie, B Anderson, KC Chin, L Shaughnessy, JD Brennan, C DePinho, RA TI High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients SO CANCER CELL LA English DT Article ID ADVERSE PROGNOSTIC-FACTOR; GLOBAL GENE-EXPRESSION; IN-SITU HYBRIDIZATION; PLASMA-CELL LEUKEMIA; CYTOGENETIC ABNORMALITIES; CANCER; MICROARRAY; GAINS; TRANSLOCATIONS; CLASSIFICATION AB To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolution analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of MM, unsupervised classification using non-negative matrix factorization (NMF) designed for array comparative genomic hybridization (aCGH) analysis uncovered distinct genomic subtypes. Additionally, we defined 87 discrete minimal common regions (MCRs) within recurrent and highly focal CNAs. Further integration with expression data generated a refined list of MM gene candidates residing within these MCRs, thereby providing a genomic framework for dissection of disease pathogenesis, improved clinical management, and initiation of targeted drug discovery for specific MM patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna & Donald Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, Dept Neurosurg, Neurosurg Serv, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM shaughnessyjohn@uams.edu; cbrennan@mskcc.org; ron_depinho@dfci.harvard.edu OI Khatry, Deepak/0000-0002-2388-9434; Brennan, Cameron/0000-0003-4064-8891; Sukhdeo, Kumar /0000-0001-8725-6081 FU NCI NIH HHS [CA84313, P50 CA100707, P01 CA78373, P50 CA93683, R01 CA099041, R01 CA93947, CA55819]; NIA NIH HHS [K08AG0103] NR 52 TC 258 Z9 270 U1 0 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2006 VL 9 IS 4 BP 313 EP 325 DI 10.1016/j.ccr.2006.03.019 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 035WZ UT WOS:000237033700009 PM 16616336 ER PT J AU Petersen, GM de Andrade, M Goggins, M Hruban, RH Bondy, M Korczak, JF Gallinger, S Lynch, HT Syngal, S Rabe, KG Seminara, D Kiein, AP AF Petersen, GM de Andrade, M Goggins, M Hruban, RH Bondy, M Korczak, JF Gallinger, S Lynch, HT Syngal, S Rabe, KG Seminara, D Kiein, AP TI Pancreatic cancer genetic epidemiology consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RISK-FACTORS; HEREDITARY PANCREATITIS; SUSCEPTIBILITY LOCUS; COLORECTAL-CANCER; BRCA2 MUTATIONS; FAMILY-HISTORY; CARCINOMA; ADENOCARCINOMA; KINDREDS; ONSET AB We have organized the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium to identify susceptibility genes in familial pancreatic cancer (FPC). The Consortium comprises seven data collection centers, a statistical genetics core, and a pathology/archival genotyping core. We recruit kindreds containing two or more affected blood relatives ascertained through incident pancreatic adenocarcinoma cases, physician referrals, and/or through Internet recruitment. Accrual to a database containing core clinical, demographic, lifestyle, and family history information from questionnaires is ongoing, along with biospecimen collection. To date, 13,147 patients have been screened for family history, of whom 476 (50% male) probands and 1,912 of their adult (99% unaffected) relatives have been enrolled. Of these, 379 kindreds meet criteria for FPC, having at least two first-degree relatives with pancreatic cancer. Cumulative incidence curves using available age of diagnosis (onset) among and affected relatives were compared with those for incident pancreatic cancer cases reported to 13 U.S. Surveillance Epidemiology and End Results (SEER) sites from 1973 to 2000 (N = 72,700). The mean age +/- SD at diagnosis among 466 PACGENE probands and 670 affected relatives was 64.1 +/- 11.8 and was 65.4 +/- 11.6 for the subset of 369 FPC probands and 429 relatives. Both samples were significantly younger than the mean age at diagnosis in the SEER population (70.0 +/- 12.1 years; differences in curves versus SEER, P < 0.001). Age at diagnosis (excluding probands) in FPC kindreds does not decrease with increasing number of affected individuals. In our sample, younger age at diagnosis was observed whether we grouped probands by recruitment sites that predominantly recruited through high-risk referrals, or through screening all pancreatic cancer patients for family history. Linkage studies are ongoing. The PACGENE Consortium will be a valuable family-based resource that will greatly enhance genetic epidemiology research in pancreatic cancer. C1 Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA. Johns Hopkins Univ, Sol Goldman Pancreat Res Ctr, Baltimore, MD USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Creighton Univ, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. RP Petersen, GM (reprint author), Mayo Clin, Coll Med, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA. EM peterg@mayo.edu RI Gallinger, Steven/E-4575-2013 FU NCI NIH HHS [P50 CA102701, R01 CA097075, R01 CA97075] NR 47 TC 72 Z9 75 U1 0 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 APR PY 2006 VL 15 IS 4 BP 704 EP 710 DI 10.1158/1055-9965.EPl-05-0734 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100017 PM 16614112 ER PT J AU Wei, EK Ma, J Pollak, MN Rifai, N Fuchs, CS Hankinson, SE Giovannucci, E AF Wei, EK Ma, J Pollak, MN Rifai, N Fuchs, CS Hankinson, SE Giovannucci, E TI C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin, and the risk of distal colorectal adenoma in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ALCOHOL-CONSUMPTION PATTERNS; I IGF-I; CANCER RISK; PHYSICAL-ACTIVITY; COLON-CANCER; POSTMENOPAUSAL WOMEN; PLASMA-INSULIN; FACTOR (IGF)-I; BLOOD-GLUCOSE; UNITED-STATES AB Background: Determinants of insulin secretion and insulin-like growth factors (IGF) have been directly associated with risk for colorectal cancer. However, few studies have evaluated whether these factors are also associated with risk of colorectal adenoma, the main precursor lesion to colorectal cancer. Methods: We identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998 and 380 controls among nondiabetic women from the cohort of 32,826 women, nested in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases and controls were individually matched on year of birth, time period of and indication(s) for endoscopy, and date of blood draw. Results: High concentrations of C-peptide, an indicator of insulin secretion, were statistically significantly associated with risk of distal colorectal adenoma [multivariable relative risk (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01-2.66; P = 0.01], even after including body mass index and physical activity in the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did not show any clear association with risk for adenoma (MVRR top versus bottom quartile, 1.08; 95% Cl, 0.56-2.07). These associations did not differ significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was associated with a nonstatistically significant increased risk of colorectal adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44). Conclusions: High HbA1c and low IGFBP-1 were not clearly associated with increased risk of distal colorectal adenoma. However, our current results and previous associations between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a role throughout the development of colorectal neoplasia. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Oncol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal, PQ, Canada. RP Wei, EK (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM esther.wei@channing.harvard.edu RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NCI NIH HHS [CA87969, CA42182, CA49449, CA90598, T32 CA 09001]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 39 TC 53 Z9 53 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 APR PY 2006 VL 15 IS 4 BP 750 EP 755 DI 10.1158/1055-9965.EPI-05-0820 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 036BF UT WOS:000237045100024 PM 16614119 ER PT J AU Gatza, E Okada, CY AF Gatza, E Okada, CY TI Adjuvant IL-15 does not enhance the efficacy of tumor cell lysate-pulsed dendritic cell vaccines for active immunotherapy of T cell lymphoma SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE dendritic cells; tumor immunity; vaccination; interleukin-15 ID INTERLEUKIN-15 TRANSGENIC MICE; MOLONEY LEUKEMIA-CELLS; NATURAL KILLER CELLS; IN-VIVO; ANTITUMOR-ACTIVITY; CYTOTOXIC CELLS; FATAL LEUKEMIA; IMMUNITY; SPECIFICITY; LYMPHOCYTES AB There has been a recent interest in using IL-15 to enhance antitumor activity in several models because of its ability to stimulate CD8(+) stop T cell expansion, inhibit apoptosis and promote memory T cell survival and maintenance. Previously, we reported that C6VL tumor lysate-pulsed dendritic cell vaccines significantly enhanced the survival of tumor-bearing mice by stimulating a potent tumor-specific CD8(+) T cell response. In this study, we determined whether IL-15 used as immunologic adjuvant would augment vaccine-primed CD8(+) T cell immunity against C6VL and further improve the survival of tumor-bearing mice. We report that IL-15 given after C6VL lysate-pulsed dendritic cell vaccines stimulated local and systemic expansion of NK, NKT and CD8(+) CD44(hi) T cells. IL-15 did not, however, augment innate or cellular responses against the tumor. T cells from mice infused with IL-15 following vaccination did not secrete increased levels of tumor-specific TNF-alpha or IFN-gamma or have enhanced C6VL-specific CTL activity compared to T cells from recipients of the vaccine alone. Lastly, IL-15 did not enhance the survival of tumor-bearing vaccinated mice. Thus, while activated- and memory-phenotype CD8(+) T cells were dramatically expanded by IL-15 infusion, vaccine-primed CD8(+) T cell specific for C6VL were not significantly expanded. This is the first account of using IL-15 as an adjuvant in a therapeutic model of active immunotherapy where there was not a preexisting pool of tumor-specific CD8(+) T cells. Our results contrast the recent studies where IL-15 was successfully used to augment tumor-reactivity of adoptively transferred transgenic CD8(+) T cells. This suggests that the adjuvant potential of IL-15 may be greatest in settings where it can augment the number and activity of preexisting tumor-specific CD8(+) T cells. C1 Univ Michigan, Sch Med, Grad Program Immunol, Ann Arbor, MI 48109 USA. Oregon Hlth & Sci Univ, Div Hematol Oncol, Dept Internal Med, Portland, OR 97239 USA. RP Portland VA Med Ctr, Div Hosp & Specialty Med, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM okadac@ohsu.edu FU NCI NIH HHS [T32CA88784]; NIAID NIH HHS [T32AI07413] NR 46 TC 2 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2006 VL 55 IS 4 BP 420 EP 432 DI 10.1007/s00262-005-0006-9 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA 001VV UT WOS:000234571700008 PM 16025264 ER PT J AU Kulke, MH Wu, BY Clark, JW Enzinger, PC Lynch, TJ Vincitore, M Michelini, A Fuchs, CS AF Kulke, MH Wu, BY Clark, JW Enzinger, PC Lynch, TJ Vincitore, M Michelini, A Fuchs, CS TI A phase II study of doxorubicin, cisplatin, and 5-fluorouracil in patients with advanced adenocarcinoma of the stomach or esophagus SO CANCER INVESTIGATION LA English DT Article DE gastric cancer; esophageal cancer; chemotherapy; doxorubicin; cisplatin; 5-fluorouracil ID ADVANCED GASTRIC-CANCER; ADVANCED ESOPHAGOGASTRIC CANCER; ADVANCED BREAST-CANCER; HIGH-DOSE METHOTREXATE; EUROPEAN-ORGANIZATION; COOPERATIVE GROUP; SUPPORTIVE CARE; PLUS CISPLATIN; FLUOROURACIL; EPIRUBICIN AB Background: The combination of epirubicin, cisplatin, and infusional 5-fluorouracil (ECF) currently represents a standard and effective regimen for the treatment of advanced gastroesophageal cancer. The use of doxorubicin as an alternative to epirubicin in the ECF regimen has not been evaluated. Methods: Thirty-two patients with metastatic adenocarcinoma of the stomach, gastroesophageal junction, or esophagus were treated with cisplatin 60 mg/m 2 and doxorubicin 30 mg/m 2 repeated every 21 days, in combination with infusional 5-fluorouracil 200 mg/m 2 /day (ACF). Results: Major objective responses were observed in 28 percent of patients (46 percent previously untreated; 13 percent previously treated), with one complete response. The median progression-free survival was 4.0 months, and the median overall survival was 5.8 months (9.3 months previously untreated; 4.5 months previously treated). The major (Grade 3-4) toxicities were neutropenia (34 percent), anorexia (31 percent), nausea (28 percent), diarrhea (19 percent), and stomatitis (16 percent). Conclusion: In comparison with historical data taken from published trials of ECF, the ACF regimen appears similar in efficacy when differences in prior treatment status are taken into account. However, ACF appears to be associated with a higher incidence of major toxicities. Our findings therefore support the continued use of epirubicin rather than doxorubicin in combination chemotherapy regimens for advanced gastroesophageal cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM matthew_kulke@dfci.harvard.edu FU NCI NIH HHS [K23 CA 093401]; NHLBI NIH HHS [K30 HL04095] NR 22 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD APR-MAY PY 2006 VL 24 IS 3 BP 229 EP 234 DI 10.1080/07357900600633924 PG 6 WC Oncology SC Oncology GA 038NF UT WOS:000237228500002 PM 16809148 ER PT J AU Hagendoorn, J Tong, R Fukamura, D Lin, QC Lobo, L Padera, TP Xu, L Kucherlapati, R Jain, RK AF Hagendoorn, J Tong, R Fukamura, D Lin, QC Lobo, L Padera, TP Xu, L Kucherlapati, R Jain, RK TI Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis SO CANCER RESEARCH LA English DT Article ID SKIN CARCINOGENESIS; MOUSE MODELS; CANCER; ANGIOGENESIS; TUMOR; TUMORIGENESIS; NORMALIZATION; VASCULATURE; THERAPY; MICE AB Recent improvements in diagnostic methods have opened avenues for detection and treatment of (pre)malignant lesions at early stages. However, due to the lack of spontaneous tumor models that both mimic human carcinogenesis and allow direct optical imaging of the vasculature, little is known about the function of blood and lymphatic vessels during the early stages of cancer development. Here, we used a spontaneous carcinogenesis model in the skin of DNTA polymerase eta-deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood vasculature that exhibited altered permeability, vessel compression, and decreased alpha-smooth muscle actin-positive perivascular cell coverage. In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, ParHeaPartners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI Padera, Timothy/0000-0002-3453-9384 FU NCEH CDC HHS [EH 11040]; NCI NIH HHS [CA 80124, CA 84301, CA 85140, CA 96915] NR 22 TC 67 Z9 67 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2006 VL 66 IS 7 BP 3360 EP 3364 DI 10.1158/0008-5472.CAN-05-2655 PG 5 WC Oncology SC Oncology GA 030TO UT WOS:000236657800006 PM 16585153 ER PT J AU Tomlins, SA Mehra, R Rhodes, DR Smith, LR Roulston, D Helgesson, BE Cao, XH Wei, JT Rubin, MA Shah, RB Chinnaiyan, AM AF Tomlins, SA Mehra, R Rhodes, DR Smith, LR Roulston, D Helgesson, BE Cao, XH Wei, JT Rubin, MA Shah, RB Chinnaiyan, AM TI TMPRSS2 : ETV4 gene fusions define a third molecular subtype of prostate cancer SO CANCER RESEARCH LA English DT Article ID EXPRESSION; TRANSLOCATIONS AB Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. Here, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified marked overexpression of ETV4 in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4 (17q21) loci are fused in this case. This result defines it third molecular subtype of prostate cancer and supports the hypothesis that dysregulation of ETS family members through fusions with TMRPSS2 may be an initiating event in prostate cancer development. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Program Bioinformat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Urol Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine St,MSI 4237, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Wei, John/E-8967-2012; OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [U01 CA 111275-01, 5P30 CA 46592, P50 CA 69568, R01 CA 97063]; NIA NIH HHS [R01 AG 21404] NR 14 TC 277 Z9 291 U1 0 U2 5 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 APR 1 PY 2006 VL 66 IS 7 BP 3396 EP 3400 DI 10.1158/0008-5472.CAN-06-0168 PG 5 WC Oncology SC Oncology GA 030TO UT WOS:000236657800013 PM 16585160 ER PT J AU Smolen, GA Muir, B Mohapatra, G Barmettler, A Kim, WJ Rivera, MN Haserlat, SM Okimoto, RA Kwak, E Dahiya, S Garber, JE Bell, DW Sgroi, DC Chin, L Deng, CX Haber, DA AF Smolen, GA Muir, B Mohapatra, G Barmettler, A Kim, WJ Rivera, MN Haserlat, SM Okimoto, RA Kwak, E Dahiya, S Garber, JE Bell, DW Sgroi, DC Chin, L Deng, CX Haber, DA TI Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis SO CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TRANSGENIC MICE; BREAST-CANCER; PROTOONCOGENE; METASTASIS; BRCA1; GENE; CARCINOMAS; MICROARRAY; EXPRESSION AB in a screen for gene copy number alterations in mouse mammary tumors initiated by loss of the Brea1 and Trp53 genes, we observed that the majority (11 of 15; 73%) had high-level amplification of wild-type Met, encoding a growth factor receptor implicated in tumor progression. Met amplification was localized to unstable double minute chromosomes and was uniquely found in mouse breast tumors driven by loss of Brca1 and Trp53. Whereas analogous MET amplification was not found in human breast cancers, the identification of a dominant somatic genetic lesion in the Brca1/Trp53 mouse model suggests that recurrent secondary hits may also exist in BRCA1-initiated human breast cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Mol Pathol Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [F32 CA 117737]; PHS HHS [P01 95281] NR 20 TC 25 Z9 25 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 APR 1 PY 2006 VL 66 IS 7 BP 3452 EP 3455 DI 10.1158/0008-5472.CAN-05-4181 PG 4 WC Oncology SC Oncology GA 030TO UT WOS:000236657800020 PM 16585167 ER PT J AU Affar, EB Luke, MP Gay, F Calvo, D Sui, GC Weiss, RS Li, E Shi, Y AF Affar, EB Luke, MP Gay, F Calvo, D Sui, GC Weiss, RS Li, E Shi, Y TI Targeted ablation of Par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; NF-KAPPA-B; CASPASE ACTIVATION; MITOCHONDRIAL DYSFUNCTION; P53-DEPENDENT APOPTOSIS; NEURONAL DEGENERATION; ONCOGENIC RAS; EXPRESSION; SURVIVAL; DEATH AB The prostate apoptosis response-4 (Par-4) protein has been shown to function as an effector of cell death in response to various apoptotic stimuli, and down-regulation of this protein has been suggested to be a key event during tumorigenesis. Several studies suggest an essential function for the COOH-terminal leucine repeats/death domain of Par-4 in mediating apoptosis. We investigated the biological role of this domain in vivo by generating knock-out mice expressing a Par-4 mutant protein lacking the COOH terminus domain. We found that the Par-4 mutant mice are viable and fertile with no overt phenotype, thus excluding an essential role for the COOH terminus domain of Par-4 in embryogenesis and developmental apoptosis. To determine the requirement of Par-4 for apoptosis, we treated primary fibroblasts with various stimuli that trigger mitochondria and membrane receptor cell death pathways. Fibroblasts isolated from Par-4 mutant mice are as sensitive as the wild-type cells to these apoptosis-inducing agents. Similar effects were observed following RNA interference (RNAi)-mediated knockdown of Par-4 in these cells. In contrast, RNAi-mediated depletion of Par-4 in HeLa cells resulted in a significant inhibition of apoptosis induced by various proapoptotic agents. Taken together, our findings provide strong genetic evidence that the proapoptotic function of Par-4 is dependent on the cellular context and raise the possibility that alterations of Par-4 function may occur during carcinogenesis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Cornell Univ, Dept Biomed Sci, Ithaca, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Louis Pasteur Ave,NRB854B, Boston, MA 02115 USA. EM yang_shi@hms.harvard.edu NR 48 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2006 VL 66 IS 7 BP 3456 EP 3462 DI 10.1158/0008-5472.CAN-05-0964 PG 7 WC Oncology SC Oncology GA 030TO UT WOS:000236657800021 ER PT J AU Battle, TE Lynch, RA Frank, DA AF Battle, TE Lynch, RA Frank, DA TI Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis SO CANCER RESEARCH LA English DT Article ID RECOMBINANT GAMMA-INTERFERON; CHRONIC LYMPHOCYTIC-LEUKEMIA; IFN-GAMMA; TISSUE INHIBITOR; IN-VIVO; TARGETED DISRUPTION; CANCER-PATIENTS; GROWTH-FACTOR; CO-REPRESSOR; TUMOR-CELLS AB To determine the role of the transcription factor signal transducer and activator of transcription (STAT) 1 on endothelial cell function, human umbilical vein endothelial cells (HUVEC) were treated with IFN-gamma, a potent activator of STAT1. IFN-gamma inhibited cell growth and tube formation of HUVECs. Although the potent proangiogenic protein vascular endothelial growth factor (VEGF) stimulated cell growth and tube formation, IFN-gamma could suppress these effects of VEGF. Transfection of HUVECs with short interfering RNA targeting STAT1 abrogated IFN-gamma-induced inhibition of HUVEC growth and tube formation, and suppressed the inhibition of VEGF-induced tube formation by IFN-gamma, indicating that STAT1 is critical for this process. IFN-gamma blocks the biological activity of VEGF through inhibition of genes necessary for the VEGF response, including angiopoietin-2, urokinase plasminogen activator, tissue inhibitor of matrix metalloproteinase-1, cyclooxygenase-2, and VEGF receptor 2. To extend these findings in vivo, the role of STAT1 in angiogenesis was examined in STAT1-deficient mice using the Matrigel in vivo angiogenesis assay. Substantial cellular infiltration and formation of vascular structures occurred in STAT1-/- mice compared with wild-type controls. These data indicate that STAT1 plays a key role in the inhibition of angiogenesis through its action within endothelial cells, and exploiting this process may be useful in treating cancers and vascular tumors. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu NR 50 TC 54 Z9 55 U1 0 U2 1 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 APR 1 PY 2006 VL 66 IS 7 BP 3649 EP 3657 DI 10.1158/0008-5472.CAN-05-3612 PG 9 WC Oncology SC Oncology GA 030TO UT WOS:000236657800043 PM 16585190 ER PT J AU Michels, KB Giovannucci, E Chan, AT Singhania, R Fuchs, CS Willett, WC AF Michels, KB Giovannucci, E Chan, AT Singhania, R Fuchs, CS Willett, WC TI Fruit and vegetable consumption and colorectal adenomas in the nurses' health study SO CANCER RESEARCH LA English DT Article ID CIGARETTE-SMOKING; UNITED-STATES; HIGH-FIBER; LOW-FAT; CANCER; RISK; DIET; PREVENTION; POLYPS; QUESTIONNAIRE AB Consumption of fruits and vegetables may confer protection from colorectal aderionias, but the limited observational and interventional evidence is inconclusive. We examined the association between fruit and vegetable consumption and the prevalence and incidence of adenomas of the distal colon and rectum in the Nurses' Health Study (NHS). We used data from 34,467 women in the NHS who had undergone colonoscopy or sigmoidoscopy during follow-up between 1980 and 1998. Consumption of fruits and vegetables was assessed in 1980, 1984, 1986, 1990, and 1994 using a semiquantitative food frequency questionnaire; 1,720 prevalent cases of adenoma of the distal colon and rectum were diagnosed between 1980 and 1998. Frequent consumption of fruit was inversely related to the risk of being diagnosed with polyps, whereas little association was found for vegetable consumption. Women who reported consuming five or more servings of fruit a day had an odds ratio (OR) of 0.60 [95% confidence interval (95% CI), 0.44-0.81] for developing colorectal adenomas compared with women who consumed only one or fewer servings of fruit per day, after adjustment for relevant covariates (P-trend = 0.001). The respective OR for vegetable consumption was 0.82 (95% CI, 0.65-1.05; P-trend = 0.1). Women who consumed four or more servings of legumes per week had a lower incidence of colorectal adenomas than women who reported consuming one serving per week or less (OR, 0.67; 95% CI, 0.51-0.90; P-trend = 0.005). Frequent consumption of fruit may reduce the risk of colorectal adenomas. C1 Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, 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. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY USA. RP Michels, KB (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM kmichels@rics.bwh.harvard.edu FU NCI NIH HHS [CA 87969]; NIDDK NIH HHS [DK 54900, P30 DK040561-11, P30 DK040561] NR 29 TC 77 Z9 80 U1 0 U2 7 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 APR 1 PY 2006 VL 66 IS 7 BP 3942 EP 3953 DI 10.1158/0008-5472.CAN-05-3637 PG 12 WC Oncology SC Oncology GA 030TO UT WOS:000236657800077 PM 16585224 ER PT J AU Yoon, SS Hochberg, EP AF Yoon, SS Hochberg, EP TI Chemotherapy is an effective first line treatment for early stage gastric mucosa-associated lymphoid tissue lymphoma SO CANCER TREATMENT REVIEWS LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; MALT LYMPHOMA; GASTROINTESTINAL-TRACT; GERMAN MULTICENTER; HELICOBACTER; SURGERY; STOMACH C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02113 USA. Harvard Univ, Sch Med, Boston, MA 02113 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02114 USA. RP Yoon, SS (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St,Yawkey 7B-7926, Boston, MA 02113 USA. NR 18 TC 1 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD APR PY 2006 VL 32 IS 2 BP 139 EP 143 DI 10.1016/j.ctrv.2006.01.006 PG 5 WC Oncology SC Oncology GA 029JP UT WOS:000236558900007 PM 16524666 ER PT J AU Liu, ZN Roberts, TM AF Liu, ZN Roberts, TM TI Human tumor mutants in the p110 alpha subunit of PI3K SO CELL CYCLE LA English DT Article DE PI3Kinase; Akt; PIK3CA; p110 alpha; p85; transformation; myristoylation ID MAMMARY EPITHELIAL-CELLS; PHOSPHOINOSITIDE 3-KINASE; HUMAN CANCER; PHOSPHATIDYLINOSITOL 3-KINASE; CATALYTIC SUBUNIT; PIK3CA MUTATIONS; BREAST-CANCER; GENE; PATHWAY; TRANSFORMATION AB The PI3K-Akt pathway is frequently upregulated in human tumors. Recently, somatic mutations of PIK3CA, encoding p110 alpha catalytic subunit of Class IA PI3Ks, have been found in various cancers. The two most common types of p110 alpha mutants, those in the helical and kinase domains, have been shown to be very potent in Akt activation and oncogenic transformation by several groups. Notably these common mutations may not enhance recruitment of p110 alpha to the plasma membrane where its substrates are located. We have investigated the effect of membrane localization on common PIK3CA tumor mutants via myristoylation. In addition we have studied a third class of less frequent mutants in the p85-binding domain, in an attempt to gain insight into p85's inhibitory effect on p110 alpha. This article briefly reviews and extends the literature on mutant forms of p110 alpha. C1 Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM thomas_roberts@dfci.harvard.edu NR 28 TC 35 Z9 36 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2006 VL 5 IS 7 BP 675 EP 677 DI 10.4161/cc.5.7.2605 PG 3 WC Cell Biology SC Cell Biology GA 053CY UT WOS:000238282900003 PM 16627990 ER PT J AU Baumgartl, J Baudler, S Scherner, M Babaev, V Makowski, L Suttles, J McDuffie, M Fazio, S Kahn, CR Hotamisligil, GS Krone, W Linton, M Bruning, JC AF Baumgartl, J Baudler, S Scherner, M Babaev, V Makowski, L Suttles, J McDuffie, M Fazio, S Kahn, CR Hotamisligil, GS Krone, W Linton, M Bruning, JC TI Myeloid lineage cell-restricted insulin resistance protects apolipoproteinE-deficient mice against atherosclerosis SO CELL METABOLISM LA English DT Article ID FACTOR-KAPPA-B; RECEPTOR SUBSTRATE-2; DIABETES-MELLITUS; OBESE SUBJECTS; GENETIC-MAP; MACROPHAGES; BINDING; NIDDM AB Inflammatory processes play an important role in the pathogenesis of vascular diseases, and insufin-resistant diabetes mellitus type 2 represents an important risk factor for the development of atherosclerosis. To directly address the role of insulin resistance in myeloid lineage cells in the development of atherosclerosis, we have created mice with myeloid lineage-specific inactivation of the insulin receptor gene. On an ApoE-deficient background, MphIRKO mice developed smaller atherosclerotic lesions. There was a dramatic decrease in LPS-stimulated IL-6 and IL-1 beta expression in the presence of macrophage autonomous insulin resistance. Consistently, while insulin-resistant IRS-2-deficient mice on an ApoE-deficient background display aggravated atherosclerosis, fetal liver cell transplantation of IRS-2(-/-)ApoE(-/-) cells ameliorated atherosclerosis in Apo-E-deficient mice. Thus, systemic versus myeloid cell-restricted insulin resistance has opposing effects on the development of atherosclerosis, providing direct evidence that myeloid lineage autonomous insulin signaling provides proinflammatory signals predisposing to the development of atherosclerosis. C1 Univ Cologne, Inst Genet, D-50931 Cologne, Germany. Ctr Mol Med Cologne, D-50931 Cologne, Germany. Univ Cologne, Klin 2 & Poliklin Innere Med, D-50931 Cologne, Germany. Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA. Harvard Univ, Sch Publ Hlth, Div Biol Sci, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02215 USA. Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Bruning, JC (reprint author), Univ Cologne, Inst Genet, D-50931 Cologne, Germany. EM jens.bruening@uni-koeln.de OI Makowski, Liza/0000-0002-5337-8037 FU NHLBI NIH HHS [F32 HL075970, F32 HL075970-01] NR 30 TC 70 Z9 72 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR PY 2006 VL 3 IS 4 BP 247 EP 256 DI 10.1016/j.cmet.2006.02.010 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 031GJ UT WOS:000236692300005 PM 16581002 ER PT J AU Inoue, H Ogawa, W Asakawa, A Okamoto, Y Nishizawa, A Matsumoto, M Teshigawara, K Matsuki, Y Watanabe, E Hiramatsu, R Notohara, K Katayose, K Okamura, H Kahn, CR Noda, T Takeda, K Akira, S Inui, A Kasuga, M AF Inoue, H Ogawa, W Asakawa, A Okamoto, Y Nishizawa, A Matsumoto, M Teshigawara, K Matsuki, Y Watanabe, E Hiramatsu, R Notohara, K Katayose, K Okamura, H Kahn, CR Noda, T Takeda, K Akira, S Inui, A Kasuga, M TI Role of hepatic STAT3 in brain-insulin action on hepatic glucose production SO CELL METABOLISM LA English DT Article ID GENE-EXPRESSION; IN-VIVO; LIVER; MICE; INTERLEUKIN-6; PROTEIN; HEPATOCYTES; INHIBITION; GLUCONEOGENESIS; INTOLERANCE AB STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production. C1 Kobe Univ, Grad Sch Med, Div Diabet & Digest & Kidney Dis, Dept Clin Mol Med, Kobe, Hyogo 6500017, Japan. Sumitomo Pharmaceut Co Ltd, Genom Sci Labs, Takarazuka, Hyogo 6650051, Japan. Kurashiki Cent Hosp, Dept Pathol, Kurashiki, Okayama 7168602, Japan. Kobe Univ, Grad Sch Med, Dept Brain Sci, Div Mol Brain Sci, Kobe, Hyogo 6500017, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Japanese Fdn Canc Res, Inst Canc, Dept Cell Biol, Tokyo 1358550, Japan. Tohoku Univ, Sch Med, Div Mol Genet, Ctr Translat & Adv Anim Res Human Dis, Sendai, Miyagi 9808575, Japan. Kyushu Univ, Med Inst Bioregulat, Div Embryon & Genet Engn, Fukuoka 8128582, Japan. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan. Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Behav Med, Kagoshima 8908520, Japan. RP Kasuga, M (reprint author), Kobe Univ, Grad Sch Med, Div Diabet & Digest & Kidney Dis, Dept Clin Mol Med, Kobe, Hyogo 6500017, Japan. EM kasuga@med.kobe-u.ac.jp RI Akira, Shizuo/C-3134-2009; Takeda, Kiyoshi/C-9331-2009 NR 30 TC 153 Z9 156 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR PY 2006 VL 3 IS 4 BP 267 EP 275 DI 10.1016/j.cmet.2006.02.009 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 031GJ UT WOS:000236692300007 PM 16581004 ER PT J AU Niess, JH Reinecker, HC AF Niess, JH Reinecker, HC TI Dendritic cells in the recognition of intestinal microbiota SO CELLULAR MICROBIOLOGY LA English DT Review ID REGULATORY T-CELLS; EPITHELIAL-CELLS; PEYERS PATCH; SALMONELLA-TYPHIMURIUM; CROHNS-DISEASE; ORAL TOLERANCE; ACTIN-BINDING; DOME REGION; IN-VIVO; IMMUNITY AB Mucosal dendritic cells (DCs) constantly survey the luminal microenvironment which contains commensal microbiota and potentially harmful organisms regulating pathogen recognition and adaptive as well as innate defense activation. Distinct mechanisms are beginning to emerge by which intestinal antigen sampling and handling is achieved ensuring specificity and contributing to redundancy in pathogen detection. Distinct DC subsets are associated with these mechanisms and regulate specific innate or adaptive immune responses to help distinguish between commensal microbiota, pathogens and self antigens. Understanding DC biology in the mucosal immune system may contribute to the unraveling of infection routes of intestinal pathogens and may aid in developing novel vaccines and therapeutic strategies for the treatment of infectious and inflammatory diseases. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammat Bowel Dis, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.harvard.edu RI Niess, Jan /E-8361-2017 OI Niess, Jan /0000-0001-6902-5650 FU NIDDK NIH HHS [DK 068181, DK 33506] NR 65 TC 51 Z9 53 U1 2 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2006 VL 8 IS 4 BP 558 EP 564 DI 10.1111/j.1462-5822.2006.00694.x PG 7 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 021LK UT WOS:000235984500003 PM 16548882 ER PT J AU Venkatesan, BA Mahimainathan, L Ghosh-Choudhury, N Gorin, Y Bhandari, B Valente, AJ Abboud, HE Choudhury, GG AF Venkatesan, BA Mahimainathan, L Ghosh-Choudhury, N Gorin, Y Bhandari, B Valente, AJ Abboud, HE Choudhury, GG TI PI 3 kinase-dependent Akt kinase and PKC epsilon independently regulate interferon-gamma-induced STAT1 alpha serine phosphorylation to induce monocyte chemotactic protein-1 expression SO CELLULAR SIGNALLING LA English DT Article DE mesangial cell; MCP-1; PI 3 kinase; PKC-epsilon; STAT1-alpha ID HUMAN MESANGIAL CELLS; FACTOR-KAPPA-B; EPITHELIAL ICAM-1 EXPRESSION; CHEMOATTRACTANT PROTEIN-1; IFN-GAMMA; FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; ENDOTHELIAL-CELLS; DIFFERENTIAL ROLE AB Monocyte chemotactic protein-1 (MCP-1) recruits activated phagocytes to the site of tissue injury. Interferon-gamma (IFN-gamma) present in the microenvironment of glomerulus acts on mesangial cells to induce local production of MCP-1. The mechanism by which IFN-gamma stimulates expression of MCP-1 is not clear. We therefore examined the role of PI 3 kinase signaling in regulating the IFN-gamma-induced MCP-1 expression in mesangial cells. Blocking PI 3 kinase activity with Ly294002 attenuated IFN-gamma-induced MCP-1 protein and mRNA expression. IFN-gamma increased Akt kinase activity in a PI 3 kinase-dependent manner. Expression of dominant negative Akt kinase inhibited serine phosphorylation of STAT1 alpha, without any effect on its tyrosine phosphorylation, and decreased IFN-gamma-induced expression of MCP-1. These data for the first time indicate a role for PI 3 kinase-dependent Akt kinase in MCP-1 expression. We have recently shown that along with Akt, PKC epsilon is a downstream target of PI 3 kinase in IFN-gamma signaling. Similar to dominant negative Akt kinase, dominant negative PKC epsilon also inhibited serine phosphorylation of STAT1 alpha without any effect on tyrosine phosphorylation. Dominant negative PKC epsilon also abrogated MAPK activity, resulting in decrease in IFN-gamma-induced MCP-1 expression. Furthermore, Akt and PKC epsilon are present together in a signaling complex. IFN-gamma had no effect on this complex formation, but did increase PKC epsilon-associated Akt kinase activity. PKC epsilon did not regulate IFN-gamma-induced Akt kinase. Finally, expression of dominant negative Akt kinase blocked IFN-gamma-stimulated MAPK activation. These data provide the first evidence that PI 3 kinase-dependent Akt and PKCF activation independently regulate MAPK activity and serine phosphorylation of STAT1 alpha. to increase expression of MCP-1. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78220 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78220 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr San Antonio, Dept Med Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78220 USA. EM choudhuryg@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925 FU NIDDK NIH HHS [P50 DK061597, R01 DK50190, R01 DK33665, R01 DK55815] NR 56 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2006 VL 18 IS 4 BP 508 EP 518 DI 10.1016/j.cellsig.2005.05.022 PG 11 WC Cell Biology SC Cell Biology GA 001PU UT WOS:000234549600012 PM 16157472 ER PT J AU Peterson, JR Lebensohn, AM Pelish, HE Kirschner, MW AF Peterson, JR Lebensohn, AM Pelish, HE Kirschner, MW TI Biochemical suppression of small-molecule inhibitors: A strategy to identify inhibitor targets and signaling pathway components SO CHEMISTRY & BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE-EXCHANGE; BINDING PROTEIN CDC42; XENOPUS EGG EXTRACTS; N-WASP; CHEMICAL GENETICS; IDENTIFICATION; COMPLEX; GTPASES; RAC AB Identification of small-molecule targets remains an important challenge for chemical genetics. We report an approach for target identification and protein discovery based on functional suppression of chemical inhibition in vitro. We discovered pirl1, an inhibitor of actin assembly, in a screen conducted with cytoplasmic extracts. Pirl1 was used to partially inhibit actin assembly in the same assay, and concentrated biochemical fractions of cytoplasmic extracts were added to find activities that suppressed pirl1 inhibition. Two activities were detected, separately purified, and identified as Arp2/3 complex and Cdc42/RhoGDI complex, both known regulators of actin assembly. We show that pirl1 directly inhibits activation of Cdc42/RhoGDI, but that Arp2/3 complex represents a downstream suppressor. This work introduces a general method for using low-micromolar chemical inhibitors to identify both inhibitor targets and other components of a signaling pathway. C1 Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Peterson, JR (reprint author), Fox Chase Canc Ctr, Div Basic Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM jeffrey.peterson@fccc.edu FU NCI NIH HHS [P30 CA006927, CA006927]; NIGMS NIH HHS [R01 GM026875, GM026875] NR 25 TC 32 Z9 33 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD APR PY 2006 VL 13 IS 4 BP 443 EP 452 DI 10.1016/j.chembiol.2006.02.009 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 040KC UT WOS:000237376400013 PM 16632257 ER PT J AU Choi, Y McCarthy, JR Weissleder, R Tung, CH AF Choi, Yongdoo McCarthy, Jason R. Weissleder, Ralph Tung, Ching-Hsuan TI Conjugation of a photosensitizer to an oligoarginine-based cell-penetrating peptide increases the efficacy of photodynamic therapy SO CHEMMEDCHEM LA English DT Article AB To improve the efficiency of intracellular delivery of photosensitizers and the efficacy of photodynamic therapy, a membrane-penetrating arginine oligopeptide (R-7) was conjugated to 5-[4-carboxyphenyl]-10,15,20-triphenyl-2,3-dihydroxychlorin (TPC). The resulting conjugate (R-7-TPC) enhanced intracellulor TPC uptake, which increased proportionally with the incubation time of the conjugate. The water solubility of the highly hydrophobic TPC photo- sensitizer was also improved after conjugation. Increased phototoxicity of R,-TPC was observed after an incubation time of only 30 min. Tumor cells mainly underwent apoptosis at lower concentrations of the photosensitizer-polyarginine conjugate, whereas necrotic cell damage become prevalent at higher concentrations. RP Choi, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01-CA99385, P50-CA86355] NR 28 TC 48 Z9 52 U1 2 U2 17 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1860-7179 J9 CHEMMEDCHEM JI ChemMedChem PD APR PY 2006 VL 1 IS 4 BP 458 EP 463 DI 10.1002/cmdc.200500036 PG 6 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V43PA UT WOS:000202945800007 PM 16892381 ER PT J AU Casserly, IP AF Casserly, IP TI The optimal revascularization strategy for multivessel coronary artery disease: The debate continues SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review ID BYPASS GRAFT-SURGERY; RANDOMIZED-TRIAL; STENT IMPLANTATION; ADVERSE OUTCOMES; RISK-FACTORS; INTERVENTION; ANGIOPLASTY; MULTICENTER AB Mortality rates were lower among patients with multivessel coronary artery disease who underwent coronary artery bypass grafting (CABG) than among similar patients who underwent percutaneous coronary intervention (PCI) in an analysis of data from New York State registries (N Engl J Med 2005; 352:2174-2183). This finding appears to run counter to the results of randomized controlled trials, which found both procedures equivalent with regard to mortality. What are we to believe? C1 Denver Vet Affairs Med Ctr, Dept Cardiol 111B, Denver, CO 80220 USA. Univ Colorado, Boulder, CO 80309 USA. RP Casserly, IP (reprint author), Denver Vet Affairs Med Ctr, Dept Cardiol 111B, 1055 Clermont St, Denver, CO 80220 USA. EM ivan.casserly@med.va.gov NR 13 TC 6 Z9 6 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD APR PY 2006 VL 73 IS 4 BP 317 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 030QY UT WOS:000236650600004 PM 16610392 ER PT J AU Gray, R Manola, J Saxman, S Wright, J Dutcher, J Atkins, M Carducci, M See, W Sweeney, C Liu, G Stein, M Dreicer, R Wilding, G DiPaola, RS AF Gray, R Manola, J Saxman, S Wright, J Dutcher, J Atkins, M Carducci, M See, W Sweeney, C Liu, G Stein, M Dreicer, R Wilding, G DiPaola, RS TI Phase II clinical trial design: Methods in translational research from the Genitourinary Committee at the Eastern Cooperative Oncology Group SO CLINICAL CANCER RESEARCH LA English DT Article ID RANDOMIZED DISCONTINUATION DESIGN; CANCER; CETUXIMAB; AGENTS; NECK; HEAD AB Given the increase in novel agents and difficulty with planning and completing many phase III studies, various phase II trial design options should be considered to more effectively guide phase III trial plans. The need for novel phase II trial designs has increased, given the number of novel molecular targeted therapies now available for testing, an abundance of cytostatic agents, and limited resources to conduct phase III studies for all interesting agents or combinations. This review will focus on options for phase II trial designs. We review randomized phase II designs with placebo control, randomized selection designs, and randomized discontinuation designs. As agents become available for testing in the clinic, the strengths and weaknesses of different phase II trial designs should be considered to optimize a trial development plan that guides phase III trial decisions more effectively. C1 Univ Med & Dent New Jersey, Canc Inst New Jersey, New Brunswick, NJ 08901 USA. Harvard Univ, Sch Publ Hlth, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Our Lady Mercy, Bronx, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Indiana Univ, Bloomington, IN USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP DiPaola, RS (reprint author), Univ Med & Dent New Jersey, Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM dipaolrs@umdnj.edu NR 13 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 1966 EP 1969 DI 10.1158/1078-0432.CCR-05-1136 PN 1 PG 4 WC Oncology SC Oncology GA 034BI UT WOS:000236899000007 PM 16609005 ER PT J AU Goetz, MP Suman, VJ Ingle, JN Nibbe, AM Visscher, DW Reynolds, CA Lingle, WL Erlander, M Ma, XJ Sgroi, DC Perez, EA Couch, FJ AF Goetz, MP Suman, VJ Ingle, JN Nibbe, AM Visscher, DW Reynolds, CA Lingle, WL Erlander, M Ma, XJ Sgroi, DC Perez, EA Couch, FJ TI A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen SO CLINICAL CANCER RESEARCH LA English DT Article ID NEGATIVE BREAST-CANCER; GENE-EXPRESSION; PROGNOSTIC FACTORS; CARCINOMAS; VALIDATION; THERAPY; TRIALS; HOXB13; CELLS; ASSAY AB Purpose: In the adjuvant treatment of estrogen receptor (ER) - positive breast cancer, additional markers are needed to identify women at high risk for recurrence. Experimental Design: We examined the association between the ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial (NCCTG 89-30-52). Results: Tumor blocks were obtained from 211 of 256 eligible patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients. The cut point for the two-gene log 2(expression ratio) that best discriminated clinical outcome (recurrence and survival) was selected and identified women with significantly worse relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS), independent of standard prognostic markers. The cut point differed as a function of nodal status [node negative (59th percentile) versus node positive (90th percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was not associated with relapse or survival. In contrast, in the node-negative cohort (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [hazard ratio (HR), 1.98; P = 0 031], DFS (HR, 2.03; P = 0.015), and OS (HR, 2.4; P = 0.014), independent of standard prognostic markers. Conclusion: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied. C1 Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Biostat, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Arcturus Biosci Inc, Mountain View, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Mol Pathol Res Unit, Boston, MA USA. Mayo Clin, Dept Med, Div Hematol & Oncol, Jacksonville, FL 32224 USA. RP Goetz, MP (reprint author), Mayo Clin, Coll Med, Dept Oncol, 200 1st St SW, Rochester, MN 55905 USA. EM goetz.matthew@mayo.edu FU NCI NIH HHS [CA 90628-03, CA-25224, CA116201, CA87898, P50 CA116201, R01-1CA112021-01] NR 37 TC 106 Z9 110 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 2080 EP 2087 DI 10.1158/1078-0432.CCR-05-1263 PN 1 PG 8 WC Oncology SC Oncology GA 034BI UT WOS:000236899000021 PM 16609019 ER PT J AU Meeran, SM Mantena, SK Katiyar, SK AF Meeran, SM Mantena, SK Katiyar, SK TI Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair SO CLINICAL CANCER RESEARCH LA English DT Article ID CYCLOBUTANE PYRIMIDINE DIMERS; GREEN TEA POLYPHENOLS; IFN-GAMMA PRODUCTION; CONTACT HYPERSENSITIVITY; TUMOR-REGRESSION; SKIN-CANCER; IMMUNE SUPPRESSION; IRRADIATED MICE; T-CELLS; IN-VIVO AB Purpose: Solar UV radiation - induced immunosuppression is considered to be a risk factor for melanoma and nonmelanoma skin cancers. We previously have shown that topical application of (-) -epigallocatechin-3-gallate (EGCG) prevents UV-induced immunosuppression in mice. We studied whether prevention of UV-induced immunosuppression by EGCG is mediated through interleukin 12 (IL-12) - dependent DNA repair. Experimental Design: IL-12 knockout (KO) mice on C3H/HeN background and DNA repair-deficient cells from xeroderma pigmentosum complementation group A (XPA) patients were used in this study. The effect of EGCG was determined on UV-induced suppression of contact hypersensitivity and UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in mice and XPA-deficient cells using immunohistochemistry and dot-blot analysis. Results: Topical treatment with EGCG prevented UV-induced suppression of the contact hypersensitivity in wild-type (WT) mice but did not prevent it in IL-12 KO mice. Injection of anti-IL-12 monoclonal antibody to WT mice blocked the preventive effect of EGCG on UV-induced immunosuppression. EGCG reduced or repaired UV-induced DNA damage in skin faster in WT mice as shown by reduced number of CPDs(+) cells and reduced the migration of CPD+ antigen-presenting cells from the skin to draining lymph nodes. In contrast, this effect of EGCG was not seen in IL-12 KO mice. Further, EGCG was able to repair UV-induced CPDs in XPA-proficient cells obtained from healthy person but did not repair in XPA-deficient cells, indicating that nucleotide excision repair mechanism is involved in DNA repair. Conclusions: These data identify anew mechanism by which EGCG prevents UV-induced immunosuppression, and this may contribute to the chemopreventive activity of EGCG in prevention of photocarcinogenesis. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [1 R01 AT002536] NR 36 TC 37 Z9 38 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 2272 EP 2280 DI 10.1158/1078-0432.CCR-05-2672 PN 1 PG 9 WC Oncology SC Oncology GA 034BI UT WOS:000236899000046 PM 16609044 ER PT J AU Atkins, MB Elder, DE Essner, R Flaherty, KT Gajewski, TF Haluska, FG Hwu, P Keilholz, U Kirkwood, JM Mier, JW Ross, MI Slingluff, CL Sondak, VK Sosman, JA Weinstock, MA King, L AF Atkins, MB Elder, DE Essner, R Flaherty, KT Gajewski, TF Haluska, FG Hwu, P Keilholz, U Kirkwood, JM Mier, JW Ross, MI Slingluff, CL Sondak, VK Sosman, JA Weinstock, MA King, L TI Innovations and challenges in melanoma: Summary statement from the first Cambridge conference SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Innovations and Challenges in Melanoma CY JUL 15-16, 2005 CL Cambridge, MA ID T-CELL-RECEPTOR; V-ALPHA-24 NKT CELLS; EARLY-STAGE MELANOMA; MULTICENTER TRIAL; SELF-EXAMINATION; CANCER-PATIENTS; MSLT-I; IMMUNOTHERAPY; SKIN; LYMPHADENECTOMY AB Innovations and Challenges in Melanoma, chaired by Michael Atkins and cochaired by Ulrich Keilholz, John Kirkwood, and Jeffrey Sosman, was held July 15 to 16, 2005, in Cambridge, Massachusetts. The conference brought together leading experts in the fields of cancer research, medical oncology, surgical oncology, anatomic pathology, dermatology, and immunotherapy who wished to advance the field of melanoma treatment by exchanging information and perspectives regarding recent advances and recommendations for further study. The conference proceedings published in this educational supplement to Clinical Cancer Research are intended to provide timely information and recommendations on how genetics, biology, and data information can enhance our understanding of melanoma biology and help inform the use of therapies for this disease. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Chicago, Chicago, IL 60637 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Free Univ Berlin, Charite, D-1000 Berlin, Germany. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Brown Univ, Providence, RI 02912 USA. InforMEDical Commun Inc, Carlisle, MA USA. RP Atkins, MB (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, 330 Brookline Ave,Kirstein 157, Boston, MA 02215 USA. EM matkins@bidmc.harvard.edu NR 38 TC 5 Z9 6 U1 1 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 APR 1 PY 2006 VL 12 IS 7 SU S BP 2291S EP 2296S DI 10.1158/1078-0432.CCR-05-2560 PN 2 PG 6 WC Oncology SC Oncology GA 035EZ UT WOS:000236984500001 PM 16609047 ER PT J AU Haluska, FG Tsao, H Wu, H Haluska, FS Lazar, A Goel, V AF Haluska, FG Tsao, H Wu, H Haluska, FS Lazar, A Goel, V TI Genetic alterations in signaling pathways in melanoma SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 1st International Conference on Innovations and Challenges in Melanoma CY JUL 15-16, 2005 CL Cambridge, MA ID PRIMARY CUTANEOUS MELANOMA; FACTOR RECEPTOR INHIBITOR; REFRACTORY SOLID TUMORS; PROTEIN-KINASE B; MALIGNANT-MELANOMA; PTEN/MMAC1 ALTERATIONS; SUPPRESSOR GENE; BRAF MUTATIONS; CELL-SURVIVAL; RAF KINASE AB Alterations in the RAS signaling cascade are almost uniformly present in melanoma. RAS itself is only infrequently mutated in melanoma although downstream of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the protein kinase B/Akt pathway. These genes are often altered in melanomas; indeed, the most frequent target of mutation in melanomas is BRAF, which is mutated in similar to 60% to 70% of superficial spreading melanomas. These mutations occur in a background that is not normal, with the CDKN2A locus also typically being mutated. We review herein the data that suggest that the distribution of the signaling mutations is important. In general, melanomas carry a mutated NRAS, a mutated BRAF, or concurrent BRAF and PTEN mutations. These data support the hypothesis that the biochemical functions of RAS are portioned by mutations in the pathways lying downstream. Moreover, these mutations have no apparent relationship to the patterns of alteration of CDKN2A and its downstream effectors. Thus, the data also suggest that successful exploitation of mutations in melanoma will be dependent on understanding not only mutations and their frequency but their genetic context as well. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Haluska, FG (reprint author), Tufts Univ New England Med Ctr, 750 Washington St, Boston, MA 02111 USA. EM FHaluska@tufts-nemc.org RI Lazar, Alexander/A-3416-2008 OI Lazar, Alexander/0000-0002-6395-4499 FU NCI NIH HHS [P50 CA 93683-01, R01 CA 095798-01A1] NR 41 TC 60 Z9 61 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 SU S BP 2301S EP 2307S DI 10.1158/1078-0432.CCR-05-2518 PN 2 PG 7 WC Oncology SC Oncology GA 035EZ UT WOS:000236984500003 PM 16609049 ER PT J AU Li, J Wang, FF Mamon, H Kulke, MH Harris, L Maher, E Wang, LL Makrigiorgos, GM AF Li, J Wang, FF Mamon, H Kulke, MH Harris, L Maher, E Wang, LL Makrigiorgos, GM TI Antiprimer quenching-based real-time PCR and its application to the analysis of clinical cancer samples SO CLINICAL CHEMISTRY LA English DT Article ID RESONANCE ENERGY-TRANSFER; QUANTITATIVE PCR; OLIGONUCLEOTIDE PROBES; CHAIN-REACTION; DNA; AMPLIFICATION; HYBRIDIZATION; POLYMERASE; FORMAT; BREAST AB Background: Nucleic acid amplification plays an increasingly important role in genetic analysis of clinical samples, medical diagnostics, and drug discovery. We present a novel quantitative PCR technology that combines the advantages of existing methods and allows versatile and flexible nucleic acid target quantification in clinical samples of widely different origin and quality. Methods: We modified one of the 2 PCR primers by use of an oligonucleotide "tail" fluorescently labeled at the 5' end. An oligonucleoticle complementary to this tail, carrying a 3' quenching molecule (antiprimer), was included in the reaction along with 2 primers. After primer extension, the reaction temperature was lowered such that the antiprimer hybridizes and quenches the fluorescence of the free primer but not the fluorescence of the double-stranded PCR product. The latter provides real-time fluorescent product quantification. This antiprimer-based quantitative real-time PCR method (aQRT-PCR) was used to amplify and quantify minute amounts of input DNA for genes important to cancer. Results: Simplex and multiplex aQRT-PCR demonstrated linear correlation (r(2) > 0.995) down to a DNA input equivalent to 20 cells. Multiplex aQRT-PCR reliably identified the HER-2 gene in microdissected breast cancer samples; in formalin-fixed, paraffin-embedded specimens; and in plasma circulating DNA from cancer patients. Adaptation to multiplex single-nucleotide polymorphism detection via allele-specific aQRT-PCR allowed correct identification of apolipoprotein B polymorphisms in 51 of 51 human specimens. Conclusion: The simplicity, versatility, reliability, and low cost of aQRT-PCR make it suitable for genetic analysis of clinical specimens. (c) 2006 American Association for Clinical Chemistry. C1 Harvard Univ, Dana Farber Canc Inst, Dept Radiat Oncol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Sch Med, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,Level L2, Boston, MA 02115 USA. EM mmakrigiorgos@partners.org FU NCI NIH HHS [1 R21 CA 111994-01, 2 T32 CA 009078-31, CA 115439-01] NR 30 TC 20 Z9 22 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2006 VL 52 IS 4 BP 624 EP 633 DI 10.1373/clinchem.2005.063321 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 028JF UT WOS:000236482700008 PM 16469859 ER PT J AU Lauer, GM Kim, AY AF Lauer, GM Kim, AY TI Spontaneous resolution of chronic hepatitis C virus infection: Are we missing something? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CD8(+) T-CELLS; HCV INFECTION; PERSISTENCE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Lauer, GM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM glauer@partners.org NR 11 TC 6 Z9 6 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 APR 1 PY 2006 VL 42 IS 7 BP 953 EP 954 DI 10.1086/500944 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 018PK UT WOS:000235777100009 PM 16511758 ER PT J AU Branda, JA Lin, TYD Rosenberg, ES Halpern, EF Ferraro, MJ AF Branda, JA Lin, TYD Rosenberg, ES Halpern, EF Ferraro, MJ TI A rational approach to the stool ova and parasite examination SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PRESERVED FECAL SPECIMENS; INTESTINAL PARASITES; ENDAMOEBA HISTOLYTICA; GIARDIA-LAMBLIA; DIARRHEA; NUMBERS; NEED AB Background. Examination of multiple stool specimens per patient to rule out parasitic infection continues to be recommended in the literature. Attractive alternatives have been proposed, such as examination of a single specimen, but data to support their use have been inconclusive. Methods. We reviewed the results of comprehensive stool ova and parasite examinations performed during a 1-year period to determine the incremental value of examining 11 specimen. Next, we implemented rejection criteria, allowing analysis of only a single specimen in most cases, and studied the impact of the change by reviewing data from a subsequent year. Results. Prior to implementation of rejection criteria, 91% of parasites were detected in the first specimen submitted, although many clinical evaluations ( 72%) involved the submission of only 1 stool specimen. When at least 3 specimens were submitted, the sensitivity of examining the first in the series was 72%. Even the latter sensitivity provides negative predictive values of similar to 98%, similar to 97%, similar to 95%, or similar to 93% when the prevalence of parasites among those tested is 5%, 10%, 15%, or 20%, respectively. Examination of additional specimens after examination of the first specimen that yielded a positive finding revealed previously undetected parasites in only 10% of cases. After the application of rejection criteria, the parasite detection rate did not change significantly. Conclusions. Comprehensive examination of a single stool specimen is sufficient for most patients, when the prevalence of infection among the tested population is up to 20%. Rational use of the stool ova and parasite examination relies on communication between clinician and laboratory, and retention of deferred specimens in case examination of additional specimens is clinically warranted. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ferraro, MJ (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, GRB 526, Boston, MA 02114 USA. EM ferraro.maryjane@mgh.harvard.edu NR 37 TC 20 Z9 20 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 APR 1 PY 2006 VL 42 IS 7 BP 972 EP 978 DI 10.1086/500937 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 018PK UT WOS:000235777100013 PM 16511762 ER PT J AU Kassutto, S Maghsoudi, K Johnston, MN Robbins, GK Burgett, NC Sax, PE Cohen, D Pae, E Davis, B Zachary, K Basgoz, N D'agata, EMC DeGruttola, V Walker, BD Rosenberg, ES AF Kassutto, S Maghsoudi, K Johnston, MN Robbins, GK Burgett, NC Sax, PE Cohen, D Pae, E Davis, B Zachary, K Basgoz, N D'agata, EMC DeGruttola, V Walker, BD Rosenberg, ES TI Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; T-CELL RESPONSES; SEXUAL TRANSMISSION; AIDS; ADHERENCE; VIREMIA; COHORT; LOAD AB Background. Treatment of acute human immunodeficiency virus type 1 ( HIV-1) infection may have unique immunologic, virological, and clinical benefits. However, the timing of treatment, optimal starting regimens, and expected response to therapy have not been defined. Methods. One hundred two subjects treated during acute and early HIV-1 infection were observed prospectively to determine the effect of time elapsed before initiation of therapy on time to virological suppression and absolute CD4(+) cell count. Subjects were divided into pre- and postseroconversion groups on the basis of HIV-1 antibody status at the time of initiation of treatment. Absolute CD4(+) cell counts were compared between these groups and with those of historical untreated persons who had experienced seroconversion. Potential predictors of time to virological suppression and CD4+ cell count at >= 12 months were assessed. Results. Ninety-nine ( 97%) of 102 subjects achieved virological suppression. The median time to suppression was 11.1 weeks ( 95% confidence interval, 9.4 - 14.9) and was independent of initial regimen. The mean CD4+ cell count at 12 months was 702 cells/mm(3) ( 95% confidence interval, 654 - 750 cells/mm(3)) and showed an increasing trend over 60 months. Treated subjects demonstrated a statistically significant gain in the CD4(+) cell count, compared with untreated historical control subjects, at >= 12 months. Comparable virological and immunologic outcomes were seen in the pre- and postseroconversion groups. Baseline virus load and nadir CD4(+) cell count predicted time to virological suppression and CD4(+) cell count at >= 12 months, respectively. Conclusions. Early treatment of HIV-1 infection is well tolerated and results in rapid and sustained virological suppression. Preservation of CD4(+) cell counts may be achieved with early therapy, independent of seroconversion status. Protease inhibitor - based and nonnucleoside reverse-transcriptase inhibitor - based regimens show comparable performance in tolerability, time to virological suppression, and CD4(+) cell count when used as a first regimen. C1 Massachusetts Gen Hosp, Clin Microbiol Lab, Div Infect Dis, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Fenway Community Hlth Ctr, Boston, MA USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, Div Infect Dis, Gray J-504,55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org RI Robbins, Gregory/F-7988-2011 FU NCRR NIH HHS [M01 RR000722, RR-00722]; NIAID NIH HHS [AI-040873, AI-35039, AI-35040, AI-35041, AI-35042, AI-35043, AI-37613, AI-37984, AI-52403, R01 AI040873, T-32 AI007433, T32 AI007433, U01 AI035043, U01 AI052403] NR 27 TC 36 Z9 37 U1 0 U2 1 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 APR 1 PY 2006 VL 42 IS 7 BP 1024 EP 1031 DI 10.1086/500410 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 018PK UT WOS:000235777100023 PM 16511771 ER PT J AU Mudgal, CS Jupiter, JB AF Mudgal, Chaitanya S. Jupiter, Jesse B. TI Plate and screw design in fractures of the hand and wrist SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID DISTAL RADIUS FRACTURES; PROXIMAL PHALANGEAL FRACTURES; INTERNAL-FIXATION; METACARPAL FRACTURES; OSTEOFIXATION DEVICES; COMPRESSION SCREWS; MINICONDYLAR PLATE; EXTERNAL FIXATION; MINIATURE PLATES; BONE SCREW AB As internal fixation of fractures of the hand and wrist has evolved, so too have the implants used for the same purpose. Implants used for the first 1/2 of the 20th century were modeled on implants used to fix long bone fractures. Consequently, they were often bulky. In addition, they often were made of materials which were ill suited to the unique functional and biomechanical requirements of the hand and wrist. As a result, outcomes of internal fixation frequently were suboptimal and complication rates were high. In the past 40 years there has been an evolution in metallurgy, biomechanics, and implant design for fracture fixation in the hand and wrist, quite unlike any other anatomic location in the body. The principal purpose of this review is to highlight these very advances. Implants now are made of highly biocompatible materials, have a low profile, can be contoured to suit individual anatomy, and provide considerably reduced rates of soft tissue irritation. These features afford surgeons the ability to fix complex injuries in a stable manner so as to institute early rehabilitation in an effort to maximize individual outcomes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand,Yawkey Ctr, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand,Yawkey Ctr, Suite 2100, Boston, MA 02114 USA. EM cmudgal@partners.org NR 64 TC 13 Z9 13 U1 0 U2 2 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 APR PY 2006 IS 445 BP 68 EP 80 DI 10.1097/01.blo.0000205887.04200.21 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119NZ UT WOS:000243020300013 PM 16601409 ER PT J AU Price, MD Padera, RF Harris, MB Vrahas, MS AF Price, Mark D. Padera, Robert F. Harris, Mitchel B. Vrahas, Mark S. TI Pathologic fracture of the patella from a gouty tophus SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Fracture of the patella is a relatively common condition seen in patients with trauma. We report one patient with known gout who sustained relatively minor trauma that resulted in a patellar fracture. An intraoperative biopsy confirmed that much of the patella had been replaced with gouty tophus. Gout is a rare cause of patellar fracture, with few documented cases. Postoperative management of patients with patella fractures secondary to gout may be routine with the addition of medical management for the underlying pathologic process. C1 Harvard Univ, Sch Med, Harvard Combined Program Orthoped Surg, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Price, MD (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg GRB 622, 55 Fruit St, Boston, MA 02114 USA. EM mdprice@partners.org NR 9 TC 6 Z9 6 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2006 IS 445 BP 250 EP 253 DI 10.1097/01.blo.0000201159.75066.de PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119NZ UT WOS:000243020300036 ER PT J AU McKeever, VM McWhirter, BT Huff, ME AF McKeever, Victoria M. McWhirter, Benedict T. Huff, Maureen E. TI Relationships between attribution style, child abuse history, and PTSD symptom severity in Vietnam veterans SO COGNITIVE THERAPY AND RESEARCH LA English DT Article; Proceedings Paper CT 109th Annual Convention of the American-Psychological-Association CY AUG 24-28, 2001 CL SAN FRANCISCO, CA SP Amer Psychol Assoc DE learned helplessness; internal-external control; child abuse; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; I-E SCALE; LEARNED HELPLESSNESS; EXTERNAL CONTROL; COMBAT VETERANS; CAUSAL MODEL; RISK-FACTORS; LOCUS; IMPACT; SAMPLE AB Relationships between learned helplessness, locus of control, child abuse histories, adult trauma exposure and subsequent PTSD symptom severity in a clinical sample of male Vietnam veterans were examined. Learned helplessness and external locus of control were not only reliably associated with each other, but also differentially associated with childhood abuse and PTSD symptom severity. Learned helplessness, in particular, evidenced significant relationships with both childhood trauma and current distress. Contrary to expectations, child abuse history was not reliably associated with combat-related PTSD. Overall results suggested that learned helplessness and external locus of control are correlated, but independent constructs with compelling links to adult psychopathology. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Oregon, Conseling Psychol & Human Serv, Eugene, OR 97403 USA. N Range Behav Hlth, Greeley, CO USA. RP McKeever, VM (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S116 ATC, Seattle, WA 98108 USA. EM Victoria.McKeever@med.va.gov NR 49 TC 6 Z9 6 U1 2 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2006 VL 30 IS 2 BP 123 EP 133 DI 10.1007/s10608-006-9018-9 PG 11 WC Psychology, Clinical SC Psychology GA 109CC UT WOS:000242284500001 ER PT J AU Tull, MT AF Tull, Matthew T. TI Extending an anxiety sensitivity model of uncued panic attack frequency and symptom severity: The role of emotion dysregulation SO COGNITIVE THERAPY AND RESEARCH LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 2004 CL New Orleans, LA SP Assoc Advancement Behav Therapy DE anxiety sensitivity; emotion; emotion regulation; panic attacks; panic disorder ID DISORDER; FEAR AB Models of panic disorder are primarily cognitive in nature, and the role of emotion regulation has not been extensively examined. This study investigates the extent to which emotion dysregulation predicts uncued panic attack frequency and symptom severity above and beyond anxiety sensitivity (AS). Participants were 77 undergraduate students reporting a recent history of uncued panic attacks. Emotion dysregulation was not found to significantly predict past year panic attack frequency above and beyond AS dimensions (fear of respiratory symptoms, publicly observable anxiety reactions, cardiovascular symptoms, and cognitive dyscontrol). Fear of respiratory symptoms emerged as the only significant predictor of panic attack frequency. However, emotion dysregulation did significantly predict panic symptom severity above and beyond AS dimensions. Results offer preliminary evidence of the differential influence of emotion dysregulation and AS on panic-related variables and suggest the need to examine emotion dysregulation as it pertains to the development and maintenance of panic-related psychopathology. C1 Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Boston Univ, Sch Med, VA Boston Hlth Care Syst, Boston, MA 02215 USA. RP Tull, MT (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM MTull@psyc.umd.edu NR 24 TC 27 Z9 31 U1 2 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2006 VL 30 IS 2 BP 177 EP 184 DI 10.1007/s10608-006-9036-7 PG 8 WC Psychology, Clinical SC Psychology GA 109CC UT WOS:000242284500005 ER PT J AU Kamholz, BW Hayes, AM Carver, CS Gulliver, SB Perlman, CA AF Kamholz, Barbara Wolfsdorf Hayes, Adele M. Carver, Charles S. Gulliver, Suzy Bird Perlman, Carol A. TI Identification and evaluation of cognitive affect-regulation strategies: Development of a self-report measure SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE coping; cognitive affect regulation; emotion regulation; mood repair; measurement of coping ID GENDER-DIFFERENCES; EMOTION REGULATION; DEPRESSED MOOD; COPING STRATEGIES; MENTAL CONTROL; INDIVIDUALS; DISTRACTION; THOUGHTS; DISASTER; STRESS AB The ability to regulate emotions is important to mental health and well-being. However, relatively little is known about the cognitive strategies people use when faced with negative affect and the extent to which these strategies reduce such affect. This may be due, in part, to the lack of a comprehensive measure of cognitive affect-regulation strategies. Three studies were conducted to develop a broad-based self-report inventory of 15 specific strategies, called the Inventory of Cognitive Affect Regulation Strategies (ICARUS). This instrument assesses strategies that are oriented toward avoidance of the feelings (e.g., mental disengagement, thoughts of suicide) or diverting attention (e.g., self-criticism/self-blame, blaming others), as well as strategies that are oriented toward approach or engagement (e.g., reframing and growth, acceptance, mindful observation). Results provide preliminary support for the internal consistency, test-retest reliability, and convergent validity of the measure. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. RP Kamholz, BW (reprint author), IA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM barbara.kamholz2@va.gov OI carver, charles/0000-0002-3688-8545 NR 79 TC 9 Z9 9 U1 4 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0147-5916 J9 COGNITIVE THER RES JI Cogn. Ther. Res. PD APR PY 2006 VL 30 IS 2 BP 227 EP 262 DI 10.1007/s10608-006-9013-1 PG 36 WC Psychology, Clinical SC Psychology GA 109CC UT WOS:000242284500009 ER PT J AU Schrenker, RA AF Schrenker, RA TI Software engineering for future healthcare and clinical systems SO COMPUTER LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Biomed Engn, Syst Engn Grp, Boston, MA 02114 USA. RP Schrenker, RA (reprint author), Massachusetts Gen Hosp, Dept Biomed Engn, Syst Engn Grp, Boston, MA 02114 USA. EM raschrenker@partners.org NR 6 TC 11 Z9 11 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0018-9162 J9 COMPUTER JI Computer PD APR PY 2006 VL 39 IS 4 BP 26 EP 32 DI 10.1109/MC.2006.139 PG 7 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA 030DD UT WOS:000236612600005 ER PT J AU Goldman, JM Jackson, JL Whitehead, SF Rausch, TL Weininger, S AF Goldman, JM Jackson, JL Whitehead, SF Rausch, TL Weininger, S TI The Medical Device "Plug-and-Play" (MD PnP) Interoperability Program SO COMPUTER LA English DT Article C1 Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Biomed Engn, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Kaiser Permanente Mid Atlantic States, Rockville, MD USA. FDA Ctr Devices & Radiol Hlth, OSEL, DESE, Rockville, MD USA. RP Goldman, JM (reprint author), Massachusetts Gen Hosp, Med Device Plug Play Interoperabil Program, Dept Anesthesia, Boston, MA 02114 USA. EM jmgoldman@partners.org; jljackson@partners.org; swhitehead@partners.org; tracy.rausch@kp.org; sandy.weininger@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0018-9162 J9 COMPUTER JI Computer PD APR PY 2006 VL 39 IS 4 BP 30 EP 31 PG 2 WC Computer Science, Hardware & Architecture; Computer Science, Software Engineering SC Computer Science GA 030DD UT WOS:000236612600007 ER PT J AU Caplan, D Chen, E AF Caplan, D Chen, E TI Using fMRI to discover cognitive operations SO CORTEX LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. EM dcaplan@partners.org FU NCRR NIH HHS [P41RR14075]; NIDCD NIH HHS [DC02146] NR 4 TC 5 Z9 5 U1 0 U2 1 PU MASSON DIVISIONE PERIODICI PI MILANO PA VIA MUZIO ATTENDOLO DETTO SFORZA 79, 20141 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2006 VL 42 IS 3 BP 393 EP 395 DI 10.1016/S0010-9452(08)70366-6 PG 3 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 049BD UT WOS:000237989500009 PM 16771045 ER PT J AU Nasraway, SA Albert, M Donnelly, AM Ruthazer, R Shikora, SA Saltzman, E AF Nasraway, SA Albert, M Donnelly, AM Ruthazer, R Shikora, SA Saltzman, E TI Morbid obesity is an independent determinant of death among surgical critically ill patients SO CRITICAL CARE MEDICINE LA English DT Review DE morbid obesity; critically ill; surgical intensive care unit; outcomes; mortality; length of stay ID BODY-MASS INDEX; INTENSIVE-CARE-UNIT; HOSPITALIZED-PATIENTS; HEART-DISEASE; MORTALITY; PREVALENCE; SURGERY; OVERWEIGHT; ILLNESS; UPDATE AB Objective. To determine whether extreme obesity (morbid obesity; body mass index >= 40 kg/m) is an independent risk factor for death among critically ill patients; this objective is most salient in the subset of patients who sustain a prolonged intensive care unit stay during which the burdens of care imposed by obesity and its consequences would become most apparent. Design: Cohort analysis of data from the Project Impact database used to catalog admissions and outcomes to a surgical intensive care unit with predetermined end point analyses of outcomes. Setting: Surgical intensive care unit serving Tufts-New England Medical Center, a tertiary care and university medical center in Boston. Patients: All critically ill surgical patients admitted to the Tufts-New England Medical Center surgical intensive care unit from January 1998 to March 2001. Interventions: Intensive care unit and hospital mortality and lengths of stay were compared with body mass index subclassified into five groups: underweight, normal weight, overweight, obese, and extremely obese. Data were examined for all admissions during the study period and for a predetermined subgroup with a prolonged intensive care unit stay (>= 4 days). Measurements and Main Results: The prevalence of obesity in the surgical intensive care unit was 26.7%; extreme obesity was observed in 6.8%. In the full cohort of patents (n = 1373), median length of stay was short (2 days) and there were no differences in mortality in patients among any of the body mass index classes. In the subgroup of prolonged stay patients (n = 406), intensive care unit and hospital mortality rates were significantly increased in extremely obese patients compared with all other patients (intensive care unit, 33.3% vs. 12.3%, p = .009; hospital, 33.3% vs. 16%, p = .045). Multvariate analysis showed that extreme obesity was an independent predictor of death in surgical critically ill patients with prolonged intensive care unit stay after controlling for age, gender, and severity of illness. The odds of death increased 7.4 times in patients with morbid obesity. Conclusions. Morbid obesity (body mass index :40 kg/m(2)) is an independent risk factor for death in surgical patients with catastrophic illness requiring prolonged intensive care. The prevalence of obesity is growing, both in the intensive care unit and in the general population. The increased risk of complications and death in this population mandates that we adapt customized processes of care to specifically address this unique and very challenging subset of patients. C1 Tufts Univ New England Med Ctr, Biostat Res Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. Cent Florida Colon & Rectal Clin, Altamonte Springs, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. RP Nasraway, SA (reprint author), Tufts Univ New England Med Ctr, Biostat Res Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. NR 42 TC 92 Z9 93 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2006 VL 34 IS 4 BP 964 EP 970 DI 10.1097/01.CCM.0000205758.18891.70 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 025YH UT WOS:000236303000005 PM 16484910 ER PT J AU Stelfox, HT Ahmed, SB Ribeiro, RA Gettings, EM Pomerantsev, E Schmidt, U AF Stelfox, HT Ahmed, SB Ribeiro, RA Gettings, EM Pomerantsev, E Schmidt, U TI Hemodynamic monitoring in obese patients: The impact of body mass index on cardiac output and stroke volume SO CRITICAL CARE MEDICINE LA English DT Article DE hemodynamic monitoring; body mass index; obesity; cardiac output; stroke volume AB Objective: Interpreting hemodynamic parameters in critically ill obese patents can be difficult as the effects of body mass index (BMI) on cardiac output (CO) and stroke volume (SV) at the extremes of body size remains unknown. We examined the relationship between BMI and both CO and SV for patients with varying body sizes. Design: Retrospective cohort analysis. Setting. A large tertiary care academic medical center. Patients: A total of 700 consecutive adults who were found to have disease-free coronary arteries and a cardiac output measurement (thermodilution or Fick method) during coronary angiography between July 1, 2000, and July 31, 2004. Measurements and Results: We examined the relationship between BMI (mean, 28 kg/m(2); range, 10.6-91.6 kg/m(2)) and cardiac hemodynamics after adjusting for demographic (age, sex) and clinical (diabetes, smoking status, valvular heart disease, medications, indications for catheterization) characteristics using multivariable regression. Body mass index was positively correlated with CO and SV. Each 1 kg/m(2) increase in BMI was associated with a 0.08 L/min (95% confidence interval [CI], 0.06-0.10; p < .001) increase in CO and 1.35 mL (95% Cl, 0.96-1.74; p < .001) increase in SV. There was no significant association between BMI and both cardiac index (0.003 L/min/M2; 95% Cl, -0.008-0.014; p = .571) and stroke volume index (0.17 mL/m(2); 95% CI, -0.03-0.37; p = .094). Conclusion: Variations in BMI translate into predictable but only modest differences in CO and SV, even at the extremes of body size. Indexing hemodynamic measurements to body surface area attenuates the effects of BMI. Body habitus should not appreciably complicate the interpretation of hemodynamic measurements. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Stelfox, HT (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM hstelfox@partners.org RI Ribeiro, Rodrigo/E-8352-2013; Ahmed, Sofia/J-7876-2015 OI Ribeiro, Rodrigo/0000-0001-8792-1512; NR 13 TC 35 Z9 36 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2006 VL 34 IS 4 BP 1243 EP 1246 DI 10.1097/01.CCM.0000208358.27005.F4 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 025YH UT WOS:000236303000043 PM 16484893 ER PT J AU Krouse, RS Mohler, MJ Wendel, CS Grant, M Baldwin, CM Rawl, SM McCorkle, R Rosenfeld, KE Ko, CY Schmidt, CM Coons, SJ AF Krouse, RS Mohler, MJ Wendel, CS Grant, M Baldwin, CM Rawl, SM McCorkle, R Rosenfeld, KE Ko, CY Schmidt, CM Coons, SJ TI The VA ostomy health-related quality of life study: objectives, methods, and patient sample SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE focus groups; ostomy; quality of life; stomas ID INFLAMMATORY BOWEL-DISEASE; VETERANS-HEALTH; COLORECTAL-CANCER; SURVEY SF-36; SURGERY; FORM; QUESTIONNAIRE; DYSFUNCTION; COLOSTOMY; AFFAIRS AB Objective: To present the design and methods of a multisite study of health-related quality of life (HR-QOL) in veterans living with ostomies. Research design and methods: Veterans from Tucson, Indianapolis, and Los Angeles VA Medical Centers were surveyed using the validated City of Hope ostomy-specific tool (mCOH-QOL-Ostomy) and the SF-36V. Cases (ostomates) had a major gastrointestinal procedure that required an intestinal stoma, while controls had similar procedures for which an ostomy was not required. Ostomy subjects were recruited for four focus groups in each of two sites divided by ostomy type (colostomy versus ileostomy) and overall mCOH-QOL-Ostomy HR-QOL score (highest versus lowest quartile). The focus groups further evaluated barriers, concerns, and adaptation methods and skills. Main outcome measures: This report presents recruitment results, reliability of survey instruments, and demographic characteristics of the sample. Results: The overall response (i.e., recruitment) rate across all sites was 48% and by site was 53%, 57%, and 37%, respectively (p < 0.001). Internal consistency reliability estimates indicated that both instruments remain reliable in this population (Cronbach's alpha for HR-QOL domains/scales: 0.71-0.96). Cases and controls were similar in demographic characteristics. Proportions of minority subjects matched projections from the site patient populations. Subjects with ostomies had significantly longer time since surgery than controls (p < 0.001). Focus groups were comprised of two to six subjects per group and demonstrated racial diversity at the Los Angeles site. Conclusions; The unique design of our study of VA patients with ostomies is an illustration of a successful mixed methods approach to HR-QOL-research. We collected meaningful quantitative and qualitative data that will be used in the development of new approaches to care that will lead to improved functioning and well-being in persons living with ostomies. Subsequent reports will provide the results of this research project. C1 So Arizona Vet Affairs Hlth Care Syst, Surg Care Line, Tucson, AZ 85723 USA. Univ Arizona, Coll Med, Tucson, AZ USA. Univ Arizona, Coll Publ Hlth, Tucson, AZ USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. Arizona State Univ, Coll Nursing SW Borderlands, Tempe, AZ USA. Indiana Univ, Sch Nursing, Indianapolis, IN 46204 USA. Yale Univ, New Haven, CT USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA. Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. RP Krouse, RS (reprint author), So Arizona Vet Affairs Hlth Care Syst, Surg Care Line, 2-112,3601 S 6th Ave, Tucson, AZ 85723 USA. EM robert.krouse@va.gov OI Baldwin, Carol/0000-0002-0732-2307; Rawl, Susan/0000-0003-2052-2853 NR 53 TC 24 Z9 24 U1 0 U2 3 PU LIBRAPHARM PI NEWBURY PA 29-35 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD APR PY 2006 VL 22 IS 4 BP 781 EP 791 DI 10.1185/030079906X96380 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 048LM UT WOS:000237948600018 PM 16684439 ER PT J AU Krupka, DC Sandberg, WS AF Krupka, Dan C. Sandberg, Warren S. TI Operating room design and its impact on operating room economics SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE operating room economics; operating room efficiency; operating room throughput; performance improvement; perioperative system design AB Purpose of review Operating rooms are high-cost/high-revenue environments. In an era of rising costs and declining reimbursement, it is essential to optimize the effectiveness of the operating room suite, maximizing throughput of profitable cases while minimizing the costs of necessary, but unprofitable, procedures. Recent findings Operating room management focuses on reducing wasted time in order to perform more cases in regular business hours, reduce overtime, or provide a better experience for staff and patients. It has been difficult to improve perioperative efficiency enough to reliably add cases during regular hours because the required time savings are so large, while most interventions can save only a few minutes per case. Recent work, however, has changed the basic paradigms for turning over operating rooms, dramatically reducing nonproductive time and increasing operating room throughput. In some situations, the additional expense required to achieve throughput improvements is more than offset by financial gains. Summary Redesigning perioperative systems can increase operating room throughput, but not all case mixes benefit from the required additional resources. Thus hospitals should choose judiciously if, and to what degree, high throughput environments are implemented. Once implemented, access to these environments can be used as an incentive for improved surgical performance. C1 [Krupka, Dan C.] Twin Peaks Grp, Sherborn, MA USA. [Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Anesthesia, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM wsandberg@partners.org FU Massachusetts General Hospital Department of Anesthesia and Critical Care (Boston, MA) FX This project was sponsored by departmental support from the Massachusetts General Hospital Department of Anesthesia and Critical Care (Boston, MA). NR 16 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD APR PY 2006 VL 19 IS 2 BP 185 EP 191 PG 7 WC Anesthesiology SC Anesthesiology GA V42RW UT WOS:000209631900013 PM 16552226 ER PT J AU Hart, PJ AF Hart, PJ TI Pathogenic superoxide dismutase structure, folding, aggregation and turnover SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DEGENERATION; COPPER-BINDING-SITE; LINKED MUTANT SOD1; CU,ZN-SUPEROXIDE DISMUTASE; TRANSGENIC MICE; FAMILIAL ALS; SPINAL-CORD; CELL-DEATH; PROTEASOMAL DEGRADATION AB Significant advances have been made during the past two years toward an understanding of the molecular basis for how mutations in human cytosolic copper-zinc superoxide dismutase (SOD1) cause the inherited form of amyotrophic lateral sclerosis (ALS). Biophysical studies suggest that the pathogenic mutations destabilize loop or beta-barrel structural elements of the protein. With few exceptions, the loss of metal ions and reduction of the intrasubunit disulfide bond enhance this destabilization. In mouse models of the disease, the formation of visible aggregates containing mutant SOD1 occurs relatively late in the lifespan, hinting that the quality control and protein turnover systems of motor neurons eventually become overwhelmed or compromised. Studies probing SOD1 turnover have suggested the possibility that proteolytic breakdown products may play a role in pathogenesis. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Biochem,Xray Crystallog Core Lab, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr,Dept Vet Affairs, San Antonio, TX 78229 USA. RP Hart, PJ (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Dept Biochem,Xray Crystallog Core Lab, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM pjhart@biochem.uthscsa.edu FU NINDS NIH HHS [R01 NS039112] NR 56 TC 75 Z9 77 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD APR PY 2006 VL 10 IS 2 BP 131 EP 138 DI 10.1016/j.cbpa.2006.02.034 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 035KU UT WOS:000237000700007 PM 16516535 ER PT J AU Jones, R Rhee, DJ AF Jones, R Rhee, DJ TI Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE intravitreal triamcinolone; ocular hypertension; review; steroid-induced glaucoma ID OPEN-ANGLE GLAUCOMA; INTRAVITREAL TRIAMCINOLONE ACETONIDE; HUMAN TRABECULAR MESHWORK; INTRAOCULAR-PRESSURE; FLUID DYNAMICS; ORGAN-CULTURE; DEXAMETHASONE; INJECTION; CELLS; GLUCOCORTICOIDS AB Purpose of review The purpose of this article is to briefly review the literature of corticosteroid-induced ocular hypertension and glaucoma, its risk factors the pathophysiology, and treatment options. In particular, literature pertaining to glaucoma in response to intravitreal triamcinolone acetonide will be reviewed. Recent findings Primary open-angle glaucoma status as a glaucoma suspect and a family history of glaucoma are risk factors for an ocular hypertensive response wit the use of corticosteroid therapy. Recent studies suggest that younger age may also be a risk factor in patients treated via the intravitreal route with corticosteroids. The mechanism of elevated intraocular pressure is increased aqueous outflow resistance owing to an accumulation of extracellular matrix material in the trabecular meshwork. Summary Corticosteroid-induced ocular hypertension and glaucoma has been recognized for more than 50 years. Knowing the risk factors, prevalence, and pathophysiology can help the clinical prevent, monitor and treat corticosteroid-induced ocular hypertension and glaucoma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. RP Rhee, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM dougrhee@aol.com NR 44 TC 137 Z9 142 U1 5 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD APR PY 2006 VL 17 IS 2 BP 163 EP 167 PG 5 WC Ophthalmology SC Ophthalmology GA 047RG UT WOS:000237895800008 PM 16552251 ER PT J AU Houser, SL AF Houser, Stuart L. TI Histopathology of discordant xenotransplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE discordant; histopathology; microangiopathy; rejection; xenograft AB Purpose of review The combination of improved regimens of immunosuppression and supportive therapies with sustained depletion of native xenoreactive antibodies that bind to donor antigens, or with genetic deletion of donor antigens, has resulted in a significant extension of graft survival in large animal models of discordant xenotransplantation. this review focusses on organ transplantation in the pig to nonhuman primate and summarizes a shifting pattern of histopathologic findings associated with xenograft rejection. Recent findings Hyperacute rejection is preventable in renal and cardiac xenografts but still problematic in pulmonary xenografts. Interstital monnuclear cell infiltrates of acute cellular rejection are no longer prominent in xenografts with prolonged survival. Acute humoral xenograft rejection has been modulated in xenograft kidneys and hearts and now involves thromotic microangiopathy as a major feature. Graft vasculopathy typical of chronic rejection has only recently been identified. Summary For most discordant xenografts, thrombotic microangiopathy challenges our understanding of acute humoral xenograft rejection, the main cause of xenograft failure. Chronic rejection may be the next hurdle in xenotransplantation. As xenograft survival is prolonged an ongoing scrutiny of the histologic features of these grafts will be crucial to our ability to characterize the pathophysiologic mechanisms of xenograft rejection or tolerance. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Houser, SL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM houser.stuart@mgh.harvard.edu NR 59 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 EI 1531-7013 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2006 VL 11 IS 2 BP 166 EP 173 DI 10.1097/01.mot.0000218931.19773.f7 PG 8 WC Transplantation SC Transplantation GA V63FL UT WOS:000204272900010 ER PT J AU Mueller, NJ Fishman, JA AF Mueller, Nicolas J. Fishman, Jay A. TI Infectious risk in xenotransplantation SO CURRENT OPINION IN ORGAN TRANSPLANTATION LA English DT Review DE exclusion; infection; porcine endogenous retrovirus; risk; screening; virus; xenotransplantation AB Purpose of review Xenotransplantation of tissues from swine into humans poses the threat of transfer of known and unknown porcine microorganisms to xenograft recipients and to the general population. Recent data are reviewed that offer a perspective on the risk for, and prevention of, xenozoonotic infections. Recent findings Progress has been-reported on the identification, monitoring, and exclusion of exogenous porcine viruses from the donor pig. Human-tropic porcine endogenous retrovirus appears to be a recombinant of porcine endogenous retrovirus types A and C. Published observations of porcine endogenous retrovirus infection of human tissues in murine models appear to be artifacts of pseudotyping of porcine viruses by murine retroviruses and may overestimate the risks posed by xenotransplantation. The role of porcine endogenous retrovirus-encoded xenoantigens in xenograft rejection is under investigation. Summary A combination of barrier derivation, early weaning, and genetic engineering may be needed to exclude potential pathogens from xenograft tissues. Mouse models are limited in utility for retroviral studies of infectivity for human tissues by the presence of pseudotyping murine leukemia viruses. Protocols for microbiologic monitoring of patients and their social and sexual contacts must precede clinical trials. Techniques exist to monitor potential infectious complications after xenotransplantation so as to allow well monitored clinical trials. C1 [Mueller, Nicolas J.] Univ Zurich Hosp, Dept Med, Div Infect Dis, CH-8091 Zurich, Switzerland. [Mueller, Nicolas J.] Univ Zurich Hosp, Hosp Epidemiol, CH-8091 Zurich, Switzerland. [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis,Transplant Infect Dis & Compromise, Boston, MA USA. RP Mueller, NJ (reprint author), Univ Zurich Hosp, Dept Med, Div Infect Dis, Ramistr 100-RAE U 74, CH-8091 Zurich, Switzerland. EM Nicolas.Mueller@usz.ch RI Infektiologie, USZ/A-6921-2011; Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 NR 43 TC 1 Z9 1 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1087-2418 J9 CURR OPIN ORGAN TRAN JI Curr. Opin. Organ Transpl. PD APR PY 2006 VL 11 IS 2 BP 180 EP 184 DI 10.1097/01.mot.0000218933.27397.50 PG 5 WC Transplantation SC Transplantation GA V63FL UT WOS:000204272900012 ER PT J AU Feldman, AS Bauer, SB AF Feldman, Adam S. Bauer, Stuart B. TI Diagnosis and management of dysfunctional voiding SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE dysfunctional elimination syndrome; dysfunctional voiding; enuresis; non-neurogenic neurogenic bladder AB Purpose of review This review will focus on the diagnosis and management of voiding dysfunction in neurologically and anatomically normal children. The discussion will highlight recent developments and research in the clinical approach as well as the etiology and classification of these disorders, Recent findings Voiding dysfunction in children encompasses a wide spectrum of clinical entities, recently classified collectively as dysfunctional elimination syndromes. Voiding dysfunction typically presents after toilet training and may originate from behavioral issues that arise around this time in childhood development. The spectrum of disorders includes urge syndrome, dysfunctional voiding with an uncoordination belween the detrusor and urinary sphincter, and enuresis. Clinical symptoms may vary from mild incontinence o severe disorders with endpoints of irreversible bladder dysfunction with vesicoureteral reflux, urinary tract infection and resulting nephropathy. Diagnosis relies heavily on a good history and physical examin ation, but also includes radiologic and urodynamic evaluation. Treatment generally consists of medical therapy primarily with anticholinergics as well as behavioral therapy to modify learned voiding patterns that contribute to the voiding dysfunction. Summary This overview of voiding dysfunction in children outlines the established approaches to its diagnosis and treatment and highlights the most recent developments in the field. C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bauer, SB (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM stuart.bauer@childrens.harvard.edu NR 48 TC 46 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2006 VL 18 IS 2 BP 139 EP 147 DI 10.1097/01.mop.0000193289.64151.49 PG 9 WC Pediatrics SC Pediatrics GA V43ZN UT WOS:000202973100009 PM 16601493 ER PT J AU Newton, AW Vandeven, AM AF Newton, Alice W. Vandeven, Andrea M. TI Unexplained infant and child death: a review of Sudden Infant Death Syndrome, Sudden Unexplained Infant Death, and child maltreatment fatalities including shaken baby syndrome SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE child maltreatment fatalities; shaken baby syndrome; sudden infant death syndrome; sudden unexplained infant death ID TRAUMATIC BRAIN-INJURY; SLEEPING ENVIRONMENT; UNITED-STATES; HEAD TRAUMA; MEADOW,ROY AB Purpose of review This review will examine the most recent published literature on Sudden Infant Death, Sudden Unexplained infant Death, infant and child death due to maltreatment, and Shaken Baby Syndrome. Recent findings New recommendations from the American Academy of Pediatrics about the evaluation and prevention of possible Sudden Infant Death Syndrome cases were published this year, with a focus not only on the Back to Sleep campaign, but other factors that may contribute to the risk of Sudden Infant Death Syndrome. Additionally, the controversial issue of bed sharing is addressed, with advice given not to bed share in the first 3 months of life. The possibility of a second sudden infant death within a family is discussed. Attention is also paid to the importance of considering inflicted injury in the differential diagnosis of every unexplained infant or child death, and the recent literature on child maltreatment deaths is reviewed. Summary The grieving family who has lost an infant should receive immediate attention and support, and a multidisciplinary investigation team should be involved as soon as possible so that a full investigation can take place. Investigation of unexplained infant or child death should always involve a thorough interview with all adults involved, as well as a proper scene investigation and post-mortem examination. C1 Childrens Hosp, Child Protect Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Child Protect Program, Boston, MA 02115 USA. Childrens Hosp, Boston, MA USA. RP Newton, AW (reprint author), Childrens Hosp, Child Protect Program, 300 Longwood Ave, Boston, MA 02115 USA. NR 27 TC 15 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2006 VL 18 IS 2 BP 196 EP 200 DI 10.1097/01.mop.0000193296.32764.1e PG 5 WC Pediatrics SC Pediatrics GA V43ZN UT WOS:000202973100019 PM 16601503 ER PT J AU Vandeven, AM Newton, AW AF Vandeven, Andrea M. Newton, Alice W. TI Update on child physical abuse, sexual abuse, and prevention SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE child neglect; child physical abuse; child sexual abuse; prevention of child maltreatment AB Purpose of review The most recent literature regarding assessment and management of child maltreatment will be considered. The current status of abuse prevention activity will also be reviewed. Recent findings Clinical practice continues to be burdened by the general lack of training and knowledge of the presenting signs and symptoms of child maltreatment by general practitioners. The need for better training is emphasized. Physician engagement in child protection is further inhibited by imprecise reporting obligations and an inadequate child protective services response by the state. Several randomized, controlled trials of home-visiting programs by professionals have demonstrated modest effects in the primary prevention of child abuse and neglect; however, the prevention of recurrent maltreatment of children who remain in the home has proved elusive. Summary Current clinician training in child maltreatment is inadequate. Research into effective education of clinicians and program effectiveness is plainly needed, and should be supported by increased funding. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Vandeven, AM (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, 300 Longwood Ave, Boston, MA 02115 USA. EM andrea.vandeven@chidrens.harvard.edu NR 31 TC 5 Z9 5 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2006 VL 18 IS 2 BP 201 EP 205 DI 10.1097/01.mop.0000193295.94646.f7 PG 5 WC Pediatrics SC Pediatrics GA V43ZN UT WOS:000202973100020 PM 16601504 ER PT J AU de Bakker, PI Furnham, N Blundell, TL DePristo, MA AF de Bakker, PI Furnham, N Blundell, TL DePristo, MA TI Conformer generation under restraints SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID AB-INITIO CONSTRUCTION; X-RAY CRYSTALLOGRAPHY; PROTEIN-STRUCTURE; POLYPEPTIDE FRAGMENTS; STRUCTURE PREDICTION; MOLECULAR-DYNAMICS; ENERGY LANDSCAPES; ROTAMER LIBRARY; REFINEMENT; RESOLUTION AB Conformational sampling by direct optimization of an all-atom energy function is ineffective and inefficient because of the ruggedness of the energy landscape. Discrete sampling schemes represent an attractive alternative for generating ensembles of conformers consistent with spatial restraints derived from empirical data. Conformational sampling is becoming increasingly important for structure prediction as the bottleneck in accurate prediction shifts from energy functions to the methods used to find low-energy conformers. Experimental structure determination remains a perennial challenge as investigators tackle larger macromolecular systems, and begin to incorporate more complete descriptions of uncertainty, heterogeneity and dynamics into their models. Computational approaches that combine dense, discrete sampling with all-atom energy evaluation and refinement may help to overcome the remaining barriers to solving these problems. C1 Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Broad Inst Harvard, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP DePristo, MA (reprint author), Harvard Univ, Dept Organism & Evolutionary Biol, 16 Divin St, Cambridge, MA 02138 USA. EM mark-depristo@harvard.edu RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 47 TC 12 Z9 12 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2006 VL 16 IS 2 BP 160 EP 165 DI 10.1016/j.sbi.2006.02.001 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038PJ UT WOS:000237234500004 PM 16483766 ER PT J AU Guo, J Chung, UI Yang, DH Karsenty, G Bringhurst, FR Kronenberg, HM AF Guo, J Chung, UI Yang, DH Karsenty, G Bringhurst, FR Kronenberg, HM TI PTH/PTHrP receptor delays chondrocyte hypertrophy via both Runx2-dependent and -independent pathways SO DEVELOPMENTAL BIOLOGY LA English DT Article DE PTH/PTHrP receptor; PTHrP; Runx2; chondrocyte differentiation ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-FORMATION; CORE-BINDING-FACTOR; PARATHYROID-HORMONE; INDIAN-HEDGEHOG; OSTEOBLAST DIFFERENTIATION; CBFA1-DEFICIENT MICE; TARGETED DISRUPTION; RUNX2 EXPRESSION; GROWTH-PLATE AB The transcription factor, Runx2, promotes chondrocyte hypertrophy, whereas parathyroid hormone-related protein (PTHrP) delays this process. To examine whether PTHrP Suppresses chondrocyte hypertrophy via Runx2-dependent or -independent pathways, Runx2 expression and chondrocyte differentiation were analyzed using bones from embryonic limbs of wild type and Runx2(-/-) mice. Treatment of cultured rudiments with PTH dramatically Suppresses Runx2 mRNA levels in hypertrophic chondrocytes. PTH-induced delay of chondrocyte hypertrophy was observed in cultured tibiae From both Runx2(-/-) and wild-type embryos. This delay was also seen after PTH administration to limbs from wild type and Runx2(-/-) mice expressing Runx2 in chondrocytes via a collagen 2 promoter-driven transgene. To further explore Runx2-dependent and -independent effects of PTHrP. we examined embryonic tibiae and femurs from littermates null for PTHrP. Runx2, or both genes, Runx2(-/-) femurs exhibited no vascular invasion or chondrocytes expressing collagen type X or osteopontin mRNA. In contrast, Runx2(-/-)/PTHrP(-/-) mice exhibited limited vascular invasion and some chondrocytes expressing collagen X or osteopontin mRNA. In both tibia and femur, Runx2(-/-)l PTHrP(-/-) mice exhibited expanded regions of proliferating chondrocytes when compared to the same regions in PTHrP(-/-) mice. These data indicate that the delayed hypertrophy induced by PTHrP is mediated by both Runx2-dependent and -independent mechanisms. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Blossom St,Thier 501, Boston, MA 02114 USA. EM hkronenberg@partners.org FU NIDDK NIH HHS [DK56246] NR 30 TC 74 Z9 77 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2006 VL 292 IS 1 BP 116 EP 128 DI 10.1016/j.ydbio.2005.12.044 PG 13 WC Developmental Biology SC Developmental Biology GA 031TN UT WOS:000236727100011 PM 16476422 ER PT J AU Sun, T Hafler, BP Kaing, S Kitada, M Ligon, KL Widlund, HR Yuk, DI Stiles, CD Rowitch, DH AF Sun, T Hafler, BP Kaing, S Kitada, M Ligon, KL Widlund, HR Yuk, DI Stiles, CD Rowitch, DH TI Evidence for motoneuron lineage-specific regulation of Olig2 in the vertebrate neural tube SO DEVELOPMENTAL BIOLOGY LA English DT Article DE motor neuron; lineage mapping; oligodendrocyte; Olig2; transcription factor; Bacterial Artificial Chromosome (BAC); cis-regulation; enhancer; neural tube ID SPINAL-CORD; MOTOR-NEURON; SONIC HEDGEHOG; OLIGODENDROCYTE DEVELOPMENT; NERVOUS-SYSTEM; BHLH PROTEINS; FLOOR PLATE; INDUCTION; CELLS; REQUIREMENT AB Within the motoneuron precursor (pMN) domain of the developing spinal cord, the bHLH transcription factor, Olig2, plays critical roles in pattern formation and the generation of motor neuron and oligodendrocyte precursors. How are the multiple functions of Olig2 regulated? We have isolated a large BAC clone encompassing the human OLIG2 locus that rescues motor neuron and oligodendrocyte development but not normal pattern formation in Olig2(-/-) embryos. Within the BAC clone, we identified a conserved 3.6 kb enhancer sub-region that directs reporter expression specifically in the motor neuron lineage but not oligodendrocyte lineage ill Vivo. Our findings indicate complex regulation of Olig2 by stage- and lineage-specific regulatory elements. They further suggest that transcriptional regulation of Olig2 is involved in segregation of pMN neuroblasts. (c) 2006 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. RP Sun, T (reprint author), Cornell Univ, Weill Med Coll, Dept Cell & Dev Biol, 1300 York Ave, New York, NY 10021 USA. EM tas2009@med.cornell.edu; david_rowitch@dfci.harvard.edu FU NINDS NIH HHS [NS047572, NS4051] NR 38 TC 13 Z9 14 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2006 VL 292 IS 1 BP 152 EP 164 DI 10.1016/j.ydbio.2005.12.047 PG 13 WC Developmental Biology SC Developmental Biology GA 031TN UT WOS:000236727100014 PM 16469306 ER PT J AU Stewart, RA Arduini, BL Berghmans, S George, RE Kanki, JP Henion, PD Look, AT AF Stewart, RA Arduini, BL Berghmans, S George, RE Kanki, JP Henion, PD Look, AT TI Zebrafish foxd3 is selectively required for neural crest specification, migration and survival SO DEVELOPMENTAL BIOLOGY LA English DT Article DE neural crest; foxd3; sympathetic; sox10; snai1b; survival; migration; specification; zebrafish ID TRANSCRIPTION FACTOR FOXD3; ENTERIC NERVOUS-SYSTEM; DORSAL-ROOT GANGLIA; CELL FATE; WILD-TYPE; EMBRYONIC ZEBRAFISH; ACTIVATION DOMAINS; MUTANT EMBRYOS; DANIO-RERIO; NO TAIL AB The vertebrate neural crest is a pluripotent cell population that generates a large variety of cell types, including peripheral neurons, cartilage and pigment cells. Mechanisms that control the patterning of the neural crest toward specific cell fates remain only partially understood. Zebrafish homozygous for the sympathetic mutation 1 (sym1) have defects in a subset of neural crest derivatives, such as peripheral neurons, glia and cartilage, but retain normal numbers of melanocytes. The sym1 mutation is a nucleotide deletion that disrupts the forkhead DNA-binding domain of the foxd3 gene, which encodes a conserved winged-helix transcription factor. We show that sym1/mutants have normal numbers of premigratory neural crest cells, but these cells express reduced levels of snai1b and sox10, implicating foxd3 as an essential regulator of these transcription factors in the premigratory neural crest. The onset of neural crest migration is also delayed in sym1mutants, and there is a reduction in the number of migratory trunk neural crest cells, particularly along the medial migration pathway. TUNEL analysis revealed aberrant apoptosis localized to the hindbrain neural crest at the 15-somite stage, indicating a critical role for foxd3 in the survival of a subpopulation of neural crest cells. These results show that foxd3 selectively specifies premigratory neural crest cells for a neuronal, glial or cartilage fate, by inducing the expression of lineage-associated transcription factors in these cells and regulating their subsequent migration. (c) 2006 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Ohio State Univ, Ctr Mol Neurobiol, Dept Neurosci, Dept Mol Genet, Columbus, OH 43210 USA. RP Kanki, JP (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM john_kanki@dfci.harvard.edu; henion.1@osu.edu; thomas_look@dfci.harvard.edu OI Berghmans, Stephane/0000-0001-5414-8674; Stewart, Rodney/0000-0003-1220-1830 FU NCI NIH HHS [CA104605]; NINDS NIH HHS [NS38115] NR 70 TC 90 Z9 92 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2006 VL 292 IS 1 BP 174 EP 188 DI 10.1016/j.ydbio.2005.12.035 PG 15 WC Developmental Biology SC Developmental Biology GA 031TN UT WOS:000236727100016 PM 16499899 ER PT J AU Passegue, E Wagers, AJ AF Passegue, E Wagers, AJ TI Regulating quiescence: New insights into hematopoietic stem cell biology SO DEVELOPMENTAL CELL LA English DT Editorial Material ID MECHANISMS C1 Univ Calif San Francisco, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA. Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Stem Cell Inst, Cambridge, MA 02138 USA. RP Passegue, E (reprint author), Univ Calif San Francisco, Dev & Stem Cell Biol Program, San Francisco, CA 94143 USA. NR 10 TC 13 Z9 16 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2006 VL 10 IS 4 BP 415 EP 417 DI 10.1016/j.devcel.2006.03.002 PG 3 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 031UP UT WOS:000236730000004 PM 16580989 ER PT J AU Rincon-Choles, H Vasylyeva, TL Pergola, PE Bhandari, B Bhandari, K Zhang, JH Wang, W Gorin, Y Barnes, JL Abboud, HE AF Rincon-Choles, H Vasylyeva, TL Pergola, PE Bhandari, B Bhandari, K Zhang, JH Wang, W Gorin, Y Barnes, JL Abboud, HE TI ZO-1 expression and phosphorylation in diabetic nephropathy SO DIABETES LA English DT Article ID JUNCTION PROTEIN ZO-1; GLOMERULAR EPITHELIAL-CELLS; HEPARAN-SULFATE PROTEOGLYCAN; TIGHT JUNCTION; SLIT DIAPHRAGM; HIGH GLUCOSE; GENE-EXPRESSION; MESANGIAL CELLS; ADHERENS JUNCTION; PERMEABILITY AB Cellular mechanisms responsible for the loss of capillary wall permselectivity in diabetic nephropathy are not well characterized. ZO-1 is a junctional protein involved in the assembly and proper function of a number of tight junctions and is also expressed at the junction of podocytes with the slit diaphragm. We investigated the effect of diabetes and high glucose concentration on the expression of ZO-1 in animal models of both type I and 2 diabetes and in rat glomerular epithelial cells. In diabetic animals, immunohistochemistry and Western blotting showed decreased expression of ZO-1 in glomeruli. Immunogold electron microscopy revealed redistribution of ZO-1 from the podocyte membrane to the cytoplasm in the diabetic animals. Exposure of rat glomerular epithelial cells to high glucose resulted in a decrease in the intensity of ZO-1 staining and redistribution of ZO-1 from the membrane to the cytoplasm, changes that are attenuated by blockade of the angiotensin 11 type 1 receptor. ZO-1 protein expression and serine and tyrosine phosphorylation of ZO-1 were also decreased in cells exposed to high glucose. These findings suggest that alterations in the content and localization of ZO-1 may be relevant to the pathogenesis of proteinuria in diabetes. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Rincon-Choles, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, MSC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choles@uthscsa.edu FU NIDDK NIH HHS [P50-DK-061597] NR 42 TC 40 Z9 48 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2006 VL 55 IS 4 BP 894 EP 900 DI 10.2337/diabetes.55.04.06.db05-0355 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 028MK UT WOS:000236491400004 PM 16567508 ER PT J AU Trief, PM Morin, PC Izquierdo, R Teresi, J Eimicke, JP Goland, R Starren, J Shea, S Weinstock, RS AF Trief, PM Morin, PC Izquierdo, R Teresi, J Eimicke, JP Goland, R Starren, J Shea, S Weinstock, RS TI Depression and glycemic control in elderly ethnically diverse patients with diabetes - The IDEATel project SO DIABETES CARE LA English DT Article ID COLUMBIA-UNIVERSITY INFORMATICS; PLACEBO-CONTROLLED TRIAL; CORONARY-HEART-DISEASE; COMPREHENSIVE ASSESSMENT; DOUBLE-BLIND; US ADULTS; PREVALENCE; SYMPTOMS; HEALTH; CARE AB OBJECTIVE - The purpose of the Study was to investigate the effect of comorbid depression on glycemic control and on response to a telemedicine case management intervention for elderly, ethnically diverse diabetic patients. RESEARCH DESIGN AND METHODS - Medicare beneficiaries in underserved areas were participants (n = 1,665) in the Informatics for Diabetes Education and Telemedicine (IDEATel) project and randomized to a telemedicine case management intervention or usual care. The data analyzed include baseline demographics (age, sex, race/effinicity, marital status, insulin use, years of education, years of diabetes, and pack-years smoked) and measures of glycemic control (HbA(1c) [AlC]), comorbidity, diabetes symptom severity, functional disability and depression, and I-year (n = 1,578) AlC. The association between depression and glycemic control was analyzed cross-sectionally and prospectively. RESULTS - At baseline, there was a significant correlation between depression and AlC and a trend for depression to predict AlC when other factors were controlled. However, in prospective analyses, depression did not predict change in AlC, either in the control or intervention group. CONCLUSIONS - In this large sample of elderly diabetic patients, a weak relationship between depression and AlC was found, but depression did not prospectively predict change in glycemic control. Thus, there is no evidence that depression should be used to exclude patients from interventions. Also, we should evaluate the impact of depression on outcomes other than glycemic control. C1 SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. Vet Affairs Med Ctr, Dept Med, Syracuse, NY USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Div Endocrinol, Syracuse, NY 13210 USA. Hebrew Home Aged, Div Res, Bronx, NY USA. Columbia Univ, Stroud Ctr, New York, NY 10027 USA. Columbia Univ, Naomi Berrie Diabet Ctr, New York, NY 10027 USA. Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. Columbia Univ, Dept Med, New York, NY 10027 USA. Columbia Univ, Dept Epidemiol, New York, NY 10027 USA. RP Trief, PM (reprint author), SUNY Upstate Med Univ, Dept Psychiat, 750 E Adams St, Syracuse, NY 13210 USA. EM triefp@upstate.edu NR 42 TC 37 Z9 37 U1 2 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2006 VL 29 IS 4 BP 830 EP 835 DI 10.2337/diacare.29.04.06.dc05-1769 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029DH UT WOS:000236538100013 PM 16567823 ER PT J AU Zhu, PC Zhang, D Chowdhury, D Martinvalet, D Keefe, D Shi, LF Lieberman, J AF Zhu, PC Zhang, D Chowdhury, D Martinvalet, D Keefe, D Shi, LF Lieberman, J TI Granzyme A, which causes single-stranded DNA damage, targets the double-strand break repair protein Ku70 SO EMBO REPORTS LA English DT Article DE granzyme A; Ku70; DNA repair; cytotoxic T lymphocyte ID MEDIATED APOPTOSIS; CELL-DEATH; CLEAVES; BAX; EXPRESSION; BINDING; KINASE; NICKS AB Granzyme A (GzmA) induces caspase- independent cell death with morphological features of apoptosis. Here, we show that GzmA at nanomolar concentrations cleaves Ku70, a key double-strand break repair (DSBR) protein, in target cells. Ku70 is cut after Arg(301), disrupting Ku complex binding to DNA. Cleaving Ku70 facilitates GzmA-mediated cell death, as silencing Ku70 by RNA interference increases DNA damage and cell death by GzmB cluster-deficient cytotoxic T lymphocytes or by GzmA and perforin, whereas Ku70 overexpression has the opposite effect. Ku70 has two known antiapoptotic effects - facilitating DSBR and sequestering bax to prevent its translocation to mitochondria. However, GzmA triggers single-stranded, not double-stranded, DNA damage, and GzmA- induced cell death does not involve bax. Therefore, Ku70 has other antiapoptotic functions in GzmA-induced cell death, which are blocked when GzmA proteolyses Ku70. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NHLBI NIH HHS [T32 HL066987]; NIAID NIH HHS [AI45587, R01 AI045587, R56 AI045587] NR 30 TC 30 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD APR PY 2006 VL 7 IS 4 BP 431 EP 437 DI 10.1038/sj.embor.7400622 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 038SO UT WOS:000237246100017 PM 16440001 ER PT J AU Prusinski, MA Chen, HY Drobnack, JM Kogut, SJ Means, RG Howard, JJ Oliver, J Lukacik, G Backenson, PB White, DJ AF Prusinski, MA Chen, HY Drobnack, JM Kogut, SJ Means, RG Howard, JJ Oliver, J Lukacik, G Backenson, PB White, DJ TI Habitat structure associated with Borrelia burgdorferi prevalence in small mammals in New York State SO ENVIRONMENTAL ENTOMOLOGY LA English DT Article DE vector ecology; Borrelia burgdorferi; Ixodes scapularis; New York; landscape ecology ID IXODES-SCAPULARIS ACARI; AMBLYOMMA-AMERICANUM ACARI; WHITE-TAILED DEER; LYME-DISEASE; PEROMYSCUS-LEUCOPUS; DAMMINI ACARI; UNITED-STATES; INFECTIOUS-DISEASE; WESTCHESTER-COUNTY; FOCAL DISTRIBUTION AB The relationship between habitat structural composition, presence of Ixodes scapularis Say (I. dammini Spielman, Clifford, Piesman, and Corwin), and the prevalence of Borrelia burgdorferi infection in small mammal populations was studied at 12 4-ba study sites selected within two perpendicular transects spanning New York State. Species-adjusted small mammal infection rates (SARs) were calculated to enable comparison of B. burgdorferi infection rates among sites with differing small mammal species composition and were used as the outcome variable in a predictive model. Sites with high SARs were characterized by lower overstory tree canopy height and basal area, increased understory coverage, substantial understory shrub coverage, decreased presence of surface water or saturated soil, high dominance values for I. scapularis, and higher tick burdens on small mammals, These differences were statistically significant from sites with moderate or low SAR values. Understory foliage height profiles were created for each study site, and significant differences in vegetation structural composition between high SAR sites and those with low or moderate SAR were documented. High SAR sites had increased density of herbaceous foliage at 0 and 25 cm, and higher shrub density at 0, 25, and 50 cm measurements above the ground, associated with I.scapularis questing success, and lower densities of sapling trees at 25, 50, and 75 cm. The structural composition of understory vegetation may dictate vector density and predict B. burgdorferi infection rates in small mammals in New York State. C1 New York State Dept Hlth, Hudson Valley Community Coll, Arthropod Borne Dis Program, Albany, NY 12237 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. New York State Dept Hlth, Arthropod Borne Dis Program, Griffin Lab, Slingerlands, NY 12159 USA. Cornell Univ, Coll Vet Med, New York State Dept Hlth, Diagnost Lab, Ithaca, NY 14853 USA. SUNY Albany, Sch Publ Hlth, Rensselaer, NY 12144 USA. RP White, DJ (reprint author), New York State Dept Hlth, Hudson Valley Community Coll, Arthropod Borne Dis Program, Empire State Plaza,Corning Tower Bldg,Room 632, Albany, NY 12237 USA. EM djw05@health.state.ny.us NR 58 TC 11 Z9 13 U1 3 U2 18 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0046-225X J9 ENVIRON ENTOMOL JI Environ. Entomol. PD APR PY 2006 VL 35 IS 2 BP 308 EP 319 PG 12 WC Entomology SC Entomology GA 033RB UT WOS:000236865500016 ER PT J AU Knake, S Halgren, E Shiraishi, H Hara, K Hamer, HM Grant, PE Carr, VA Foxe, D Camposano, S Busa, E Witzel, T Hamalainen, MS Ahlfors, SP Bromfield, EB Black, PM Bourgeois, BF Cole, AJ Cosgrove, GR Dworetzky, BA Madsen, JR Larsson, PG Schomer, DL Thiele, EA Dale, AM Rosen, BR Stufflebeam, SM AF Knake, S Halgren, E Shiraishi, H Hara, K Hamer, HM Grant, PE Carr, VA Foxe, D Camposano, S Busa, E Witzel, T Hamalainen, MS Ahlfors, SP Bromfield, EB Black, PM Bourgeois, BF Cole, AJ Cosgrove, GR Dworetzky, BA Madsen, JR Larsson, PG Schomer, DL Thiele, EA Dale, AM Rosen, BR Stufflebeam, SM TI The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients SO EPILEPSY RESEARCH LA English DT Article DE MEG; epilepsy surgery; EEG; non-invasive; irritative zone ID TEMPORAL-LOBE EPILEPSY; EPILEPTIFORM ACTIVITY; VIDEO-EEG; MAGNETOENCEPHALOGRAPHY; LOCALIZATION; BRAIN; ELECTROENCEPHALOGRAPHY; COMPLICATIONS; CHILDREN; YIELD AB Obective: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. Methods: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. Results: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). Conclusion: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. Univ Marburg, Dept Neurol, Interdisciplinary Epilepsy Ctr, D-35033 Marburg, Germany. Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Natl Ctr Epilepsy, Sandvika, Norway. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Knake, S (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM knake@staff.uni-marburg.de RI Dale, Anders/A-5180-2010; Shiraishi, Hideaki/A-8427-2012; Hamalainen, Matti/C-8507-2013; Witzel, Thomas/P-1402-2014; Ahlfors, Seppo/P-3644-2016; OI Dworetzky, Barbara/0000-0002-3364-2347 FU NCRR NIH HHS [P41RR14075, P41 RR014075]; NINDS NIH HHS [NS18741, NS44623, R01 NS018741, R01 NS044623] NR 27 TC 73 Z9 75 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD APR PY 2006 VL 69 IS 1 BP 80 EP 86 DI 10.1016/j.eplepsyres.2006.01.001 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 039CT UT WOS:000237278500007 PM 16516443 ER PT J AU Chen, AA Wood, MJ Krauser, DG Baggish, AL Tung, R Anwaruddin, S Picard, MH Januzzi, JL AF Chen, AA Wood, MJ Krauser, DG Baggish, AL Tung, R Anwaruddin, S Picard, MH Januzzi, JL TI NT-proBNP levels, echocardiographic findings, and outcomes in breathless patients: results from the ProBNP Investigation of Dyspnoea in the Emergency Department (PRIDE) echocardiographic substudy SO EUROPEAN HEART JOURNAL LA English DT Article DE natriuretic peptides; heart failure; echocardiography ID BRAIN NATRIURETIC PEPTIDE; CONGESTIVE-HEART-FAILURE; VENTRICULAR SYSTOLIC FUNCTION; IDIOPATHIC-DILATED CARDIOMYOPATHY; INCREMENTAL PROGNOSTIC VALUE; EJECTION FRACTION; CARDIOVASCULAR EVENTS; HOSPITALIZED-PATIENTS; DIASTOLIC FUNCTION; DOPPLER-ECHOCARDIOGRAPHY AB Aims The objective of this study was to determine the integrative utility of measuring plasma NT-proBNP levels with echocardiography in the evaluation of dyspnoeic patients. Methods and results Of 599 emergency department patients enrolled in a clinical study of NT-proBNP at a tertiary-care hospital, 134 (22%) had echocardiographic results available for analysis. Echocardiographic parameters correlating with NT-proBNP levels were determined using multivariable linear-regression analysis. Independent predictors of 1-year mortality were determined using Cox-proportional hazard analysis. Independent relationships were found between NT-proBNP levels and ejection fraction (P=0.012), tissue Doppler early and late mitral annular diastolic velocities (P=0.007 and 0.018), right ventricular (RV) hypokinesis (P=0.006), and tricuspid regurgitation severity (P < 0.001) and velocity (P=0.007). An NT-proBNP level < 300 pg/mL had a negative predictive value of 91% for significant left ventricular systolic and diastolic dysfunction. Overall 1-year mortality was 20.1% and was independently predicted by NT-proBNP level [HR 8.65, 95% confidence interval (CI) 2.7-27.8, P=0.0003], ejection fraction (HR 0.95, 95% CI 0.91-0.99, P=0.009), RV dilation (HR 2.98, 95% CI 1.05-12.8, P=0.04), and systolic blood pressure (HR 0.97, 95% CI 0.96-0.99, P=0.01). Conclusion NT-proBNP levels correlate with, and provide important prognostic information beyond, echocardiographic parameters of cardiac structure and function. Routine NT-proBNP testing may thus be useful to triage patients to more timely or deferred echocardiographic evaluation. C1 Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Yawkey 5984,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 43 TC 74 Z9 86 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2006 VL 27 IS 7 BP 839 EP 845 DI 10.1093/eurheartj/ehi811 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 023EB UT WOS:000236107200017 PM 16510467 ER PT J AU Rollins, BJ AF Rollins, BJ TI Inflammatory chemokines in cancer growth and progression SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE cancer; inflammation; chemokine; angiogenesis; monocyte ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MACROPHAGE CHEMOATTRACTANT PROTEIN-1; DENDRITIC CELL MATURATION; NON-HODGKIN LYMPHOMAS; HUMAN-BREAST-CANCER; TUMOR-GROWTH; CC-CHEMOKINE; IN-VIVO; GENE-TRANSFER; LUNG-CANCER AB Leukocyte infiltration is a cardinal feature of almost all cancers. Chemokines are generally responsible for eliciting local accumulation of inflammatory cells and they appear to play the same role in the formation of peri- and intra-tumoural infiltrates. Chronic inflammation predisposes to cancer formation and progression, and it is likely that the chemokine system contributes to this process. In part, this may be a consequence of its ability to attract mononuclear cells to cancer sites, where they provide growth or angiogenic factors that enhance cancer development. However, accumulating evidence also points to a direct effect of chemokines on cancer cells that express chemokine receptors. In particular, some chemokines can activate anti-apoptotic pathways in these cells. By either mechanism, tumour cells that secrete and/or respond to chemokines would have a selective advantage. This provides another example of cancer's ability to co-opt host systems in order to promote tumour progression. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM barrett_rollins@dfci.harvard.edu FU NCI NIH HHS [CA 53091] NR 103 TC 109 Z9 114 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 2006 VL 42 IS 6 BP 760 EP 767 DI 10.1016/j.ejca.2006.01.002 PG 8 WC Oncology SC Oncology GA 040KJ UT WOS:000237377100010 PM 16510278 ER PT J AU Daniel, RW Vander Salm, TJ Ali, IS Agnihotri, AK Bohmer, RMJ Torchiana, DF AF Daniel, RW Vander Salm, TJ Ali, IS Agnihotri, AK Bohmer, RMJ Torchiana, DF TI Prospective assessment of intraoperative precursor events during cardiac surgery SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery/13th Annual Meeting of the European-Society-of-Thoracic-Surgeons CY SEP 25-28, 2005 CL Barcelona, SPAIN SP European Assoc Cardio Thorac Surg, European Soc Thorac Surg ID MEDICAL ERRORS; ADVERSE EVENTS; MISHAPS; CARE AB Objective: Increasing attention has been afforded to the ubiquity of medical error and associated adverse events in medicine. There remains little data on the frequency and nature of precursor events in cardiac surgery, and we sought to characterize this. Methods: Detailed, anonymous information regarding intraoperative precursor events (which may result in adverse events) was collected prospectively from six key members of the operating team during 464 major adult cardiac surgical cases at three hospitals and were analyzed with univariable statistical methods. Results: During 464 cardiac surgical procedures, 1627 reports of problematic precursor events were collected for an average of 3.5 and maximum of 26 per procedure. 73.3% of cases had at least one recorded event. One-third (33.3%) of events occurred prior to the first incision, and 31.2% of events occurred while on bypass. While 68.0% of events were regarded as minor in severity (e.g., delays and missing equipment), a substantial proportion (32.0%) was considered major and included anastomotic problems, pump failure, and drug errors. Most problems (90.4%) were reported as being compensated for, although many (30.9%) were never discussed among the team. Major events were more likely to be discussed (p < 0.0001) and less likely to have been previously encountered (p = 0.0005). Perceptions of the severity and compensation of events varied across the team, as did temporal patterns of reporting (p < 0.0001). Conclusions: A wide range of problematic precursor events occurs during the majority of cardiac surgery procedures. Attention to causes and ways of preventing these precursor events could have an impact on the rate of significant errors and improve the safety of cardiac surgery. (c) 2006 Elsevier B.V. All rights reserved. C1 Maritime Heart Ctr, Halifax, NS, Canada. N Shore Med Ctr, Salem, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Business, Boston, MA 02163 USA. RP Ali, IS (reprint author), Queen Elizabeth II Hlth Sci Ctr, Div Cardiac Surg, 1796 Summer St,Suite 2269, Halifax, NS B3H 3A7, Canada. EM imtiaz.ali@dal.ca NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD APR PY 2006 VL 29 IS 4 BP 447 EP 455 DI 10.1016/j.ejcts.2006.01.001 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 036BW UT WOS:000237046900005 ER PT J AU Zickmund, SL Bryce, CL Blasiole, JA Shinkunas, L LaBrecque, DR Arnold, RM AF Zickmund, Susan L. Bryce, Cindy L. Blasiole, Julie A. Shinkunas, Laura LaBrecque, Douglas R. Arnold, Robert M. TI Majority of patients with hepatitis C express physical, mental, and social difficulties with antiviral treatment SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE adherence; antiviral therapy; depression; fatigue; hepatitis C; quality of life ID RECEIVING INTERFERON-ALPHA; QUALITY-OF-LIFE; PEGINTERFERON ALPHA-2A; COMBINATION THERAPY; RIBAVIRIN; ADHERENCE; DEPRESSION; MORBIDITY; ANXIETY; IMPACT AB Objective The hepatitis C virus can be successfully treated in up to 60% of infected patients. However, treatment is long and is associated with significant side-effects. We investigated difficulties with this treatment as it is an important factor in patient adherence. Methods Patients receiving hepatitis C treatment in a tertiary referral center were enrolled in a cross-sectional study. Demographic data, functional and emotional status, and co-morbidities were collected from patients or abstracted from the medical records. All participants underwent a semistructured interview, which was analysed by blinded coders. Results A total of 65 patients (mean age 46.1 years; 38.5% women) were enrolled. Fifty-two (80%) described moderate to severe problems attributed to treatment, with a predominance of physical difficulties (fatigue 74% of cases; flu-like symptoms 32%). Approximately one third of patients (38%) experienced depression during treatment. In 31% of cases, physical or emotional problems forced patients to quit their jobs or reduce employment. One fifth attributed deteriorating relationships with friends and family to adverse treatment effects. Necessary lifestyle adjustments, such as alcohol abstinence, caused frictions with friends in 22% of the participants. Conclusions Our findings show a high prevalence of significant adverse effects in patients undergoing antiviral therapy. Whereas the nature and severity of these adverse reactions is consistent with earlier reports, we identified implications with worsening private and professional relationships. To encourage appropriate levels of adherence, healthcare providers should seek information about these indirect treatment effects as they monitor their patients on therapy. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ Iowa, Sch Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Univ Iowa Hosp & Clin, Dept Internal Med, Iowa City, IA 52242 USA. RP Zickmund, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 151C-U Univ Dr C, Pittsburgh, PA 15240 USA. EM susan.zickmund@med.va.gov OI Bryce, Cindy/0000-0001-6356-6675 FU NHLBI NIH HHS [HL07121] NR 27 TC 16 Z9 19 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD APR PY 2006 VL 18 IS 4 BP 381 EP 388 DI 10.1097/00042737-200604000-00011 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 126AI UT WOS:000243484200011 PM 16538109 ER PT J AU Qian, XS Agematsu, K Freeman, GJ Tagawa, Y Sugane, K Hayashi, T AF Qian, XS Agematsu, K Freeman, GJ Tagawa, Y Sugane, K Hayashi, T TI The ICOS-ligand K-H2, expressed on human type II alveolar epithelial cells, plays a role in the pulmonary host defense system SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE alveolar epithelial cell; B7-H2; CD4(+) T cell; ICOS; IFN-gamma ID INDUCIBLE COSTIMULATOR-LIGAND; GERMINAL CENTER FORMATION; ANTIGEN-PRESENTING CELLS; COMPLEX CLASS-I; CD4(+) T-CELLS; NF-KAPPA-B; CRYPTOCOCCUS-NEOFORMANS; IMMUNE-RESPONSES; CO-STIMULATION; MOLECULE AB The mechanism of immune defense against pathogens in the lung, has so far been poorly understood. Here, we show that human type II alveolar epithelial cells play a key role in defense via interactions between B7 homolog (B7h), also known as ICOS ligand, and its receptor ICOS expressed on activated T cells. The A549 alveolar type II cell line abundantly expresses B7-H2, CD40 and B7-1, but not B7-2 or hGL50. TNF-alpha significantly induced B7-H2 and CD40 expression by A549 cells, but had no effect on B7-1 or B7-2 expression. TNF-alpha-deficient mice exhibited low B7-H2 expression on alveolar epithelial cells in comparison with wild-type mice. Co-culture of TNF-alpha pre-stimulated A549 cells with CD4(+) T cells promoted CD154 expression, CD4(+) T cell proliferation and cytokine production, especially IFN-gamma. Monocyte-derived TNF-alpha in combination with IFN-gamma and LPS markedly induced B7-H2 expression in A549 cells. This study thus identifies a unique costimulatory pathway via alveolar epithelial type II cells that preferentially affects T helper cell function, implying that alveolar epithelial type II cells play a crucial role in innate immunity in the lung by regulating IFN-gamma-synthesis via B7-H2/ICOS interactions. C1 Shinshu Univ, Dept Immunol & Infect Dis, Grad Sch Med, Matsumoto, Nagano 3908621, Japan. Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Dept Med,Med Sch, Boston, MA 02115 USA. Tokyo Inst Technol, Dept Biomol Engn, Yokohama, Kanagawa 227, Japan. RP Hayashi, T (reprint author), Shinshu Univ, Dept Immunol & Infect Dis, Grad Sch Med, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan. EM takuma-h@sch.md.shinshu-u.ac.jp RI Tagawa, Yoh-ichi/F-7216-2011 NR 50 TC 14 Z9 18 U1 0 U2 1 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 APR PY 2006 VL 36 IS 4 BP 906 EP 918 DI 10.1002/eji.200535253 PG 13 WC Immunology SC Immunology GA 035DH UT WOS:000236979900013 PM 16552709 ER PT J AU Siebert, U Sroczynski, G Hillemanns, P Engel, J Stabenow, R Stegmaier, C Voigt, K Gibis, B Holzel, D Goldie, SJ AF Siebert, U Sroczynski, G Hillemanns, P Engel, J Stabenow, R Stegmaier, C Voigt, K Gibis, B Holzel, D Goldie, SJ TI The German Cervical Cancer Screening Model: development and validation of a decision-analytic model for cervical cancer screening in Germany SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE cervical cancer; decision analysis; Markov model; screening ID HUMAN-PAPILLOMAVIRUS INFECTION; COST-EFFECTIVENESS; NATURAL-HISTORY; CLINICAL BENEFITS; INTRAEPITHELIAL NEOPLASIA; WOMEN; HPV; STRATEGIES; RISK; ABNORMALITIES AB Background: We sought to develop and validate a decision-analytic model for the natural history of cervical cancer for the German health care context and to apply it to cervical cancer screening. Methods: We developed a Markov model for the natural history of cervical cancer and cervical cancer screening in the German health care context. The model reflects current German practice standards for screening, diagnostic follow-up and treatment regarding cervical cancer and its precursors. Data for disease progression and cervical cancer survival were obtained from the literature and German cancer registries. Accuracy of Papanicolaou ( Pap) testing was based on meta-analyses. We performed internal and external model validation using observed epidemiological data for unscreened women from different German cancer registries. The model predicts life expectancy, incidence of detected cervical cancer cases, lifetime cervical cancer risks and mortality. Results: The model predicted a lifetime cervical cancer risk of 3.0% and a lifetime cervical cancer mortality of 1.0%, with a peak cancer incidence of 84/ 100 000 at age 51 years. These results were similar to observed data from German cancer registries, German literature data and results from other international models. Based on our model, annual Pap screening could prevent 98.7% of diagnosed cancer cases and 99.6% of deaths due to cervical cancer in women completely adherent to screening and compliant to treatment. Extending the screening interval from 1 year to 2, 3 or 5 years resulted in reduced screening effectiveness. Conclusions: This model provides a tool for evaluating the long-term effectiveness of different cervical cancer screening tests and strategies. C1 UMIT, Univ Hlth Sci, Dept Publ Hlth, Eduard Wallnofer Zentrum 1, A-6060 Hall In Tirol, Austria. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02115 USA. Univ Munich, Program Hlth Technol Assessment, Munich, Germany. Univ Munich, Inst Med Informat, Munich, Germany. Univ Jena, Dept Obstet & Gynecol, D-6900 Jena, Germany. Univ Munich, Munich Canc Registry Munich Comprehens Canc Ctr, Munich, Germany. Tech Univ Munich, D-8000 Munich, Germany. Saarland Canc Registry, Saarbrucken, Germany. Natl Assoc Statutory Hlth Insurance, Natl Dept Hlth Care Qual, Berlin, Germany. COmmon Can Registry Fed States Berlin Brandenburg, Berlin, Germany. RP Siebert, U (reprint author), UMIT, Univ Hlth Sci, Dept Publ Hlth, Eduard Wallnofer Zentrum 1, A-6060 Hall In Tirol, Austria. EM uwe.siebert@umit.at NR 50 TC 32 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2006 VL 16 IS 2 BP 185 EP 192 DI 10.1093/eurpub/cki163 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027SG UT WOS:000236435100017 PM 16469759 ER PT J AU Gong, MN Thompson, BT Williamsl, PL Zhou, W Wang, MZ Pothier, L Christiani, DC AF Gong, MN Thompson, BT Williamsl, PL Zhou, W Wang, MZ Pothier, L Christiani, DC TI Interleukin-10 polymorphism in position-1082 and acute respiratory distress syndrome SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE acute respiratory distress syndrome; interleukin-10; mortality; polymorphism ID COMMUNITY-ACQUIRED PNEUMONIA; SYSTEMIC INFLAMMATORY RESPONSE; ACUTE-RENAL-FAILURE; SEPTIC SHOCK; PROMOTER POLYMORPHISM; GENE PROMOTER; CYTOKINE PRODUCTION; ASSOCIATION; MORTALITY; SEPSIS AB The GG genotype of the interleukin (IL)-10 promoter polymorphism in position -1082 (-1082GG) has been associated with increased IL-10 production. The current authors hypothesised that the -1082GG genotype is associated with the development of, and outcomes in, acute respiratory distress syndrome (ARDS). A nested case-control study was conducted in 211 Caucasian cases of ARDS and 429 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for organ failure and 60-day mortality. The -1082GG genotype was associated with the development of ARDS, but only in the presence of a significant interaction between the -1082GG genotype and age. Among patients with ARDS, the -1082GG genotype was associated with decreased severity of illness on admission, lower daily organ dysfunction scores and lower 60-day mortality. In conclusion, the high interleukin-10-producing -1082GG genotype may be associated with variable odds for acute respiratory distress syndrome development depending on age. Among those with acute respiratory distress syndrome, the -1082GG genotype is associated with lower mortality and organ failure. Further studies are needed to confirm these findings. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Med, Div Pulm & Crit Care Med, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu FU NHLBI NIH HHS [K23 HL067197, K23 HL67197, R01 HL060710, R01 HL60710]; NIEHS NIH HHS [T32 ES007069, T32 ES07069]; NIMHD NIH HHS [L32 MD000662, L32 MD000662-02] NR 45 TC 58 Z9 66 U1 1 U2 2 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD APR PY 2006 VL 27 IS 4 BP 674 EP 681 DI 10.1183/09031936.06.00046405 PG 8 WC Respiratory System SC Respiratory System GA 030OD UT WOS:000236643100006 PM 16585075 ER PT J AU Coon, DR Roberts, DJ Loscertales, M Kradin, R AF Coon, DR Roberts, DJ Loscertales, M Kradin, R TI Differential epithelial expression of SHH and FOXF1 in usual and nonspecific interstitial pneumonia SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE sonic hedgehog; Foxfl; pulmonary fibrosis; usual interstitial pneumonia; nonspecific interstitial pneumonia ID SONIC HEDGEHOG SHH; SIGNALING PATHWAY; LUNG; CANCER; GROWTH; MORPHOGENESIS; ACTIVATION; FREAC-1; BIOPSY; TARGET AB Morphogenetic factors have been shown to play a role in embryogenesis and post-embryonic disease. Interstitial pulmonary fibrosis is a chronic and often progressive disorder that can lead to end-stage cystic lung. Its two major subtypes, usual interstitial pneumonitis (UIP) and nonspecific interstitial pneumonitis (NSIP), differ in their response to immunosuppressive regimens, with UIP having a significantly worse prognosis. The clinical and histologic overlap between these disorders is substantial, and there are no ancillary findings that can accurately distinguish them. We examined surgical and autopsy specimens of lung in 13 cases of patients with either UIP or the fibrotic variant of NSIP (NSIP-F) for their expression of Sonic hedgehog (Shh) and Foxf1 in situ. We identified a pattern of strong Shh expression with weak expression of Foxf1 in all cases of UIP and a complementary expression of Shh and Foxf1 in cases of NSIP-F. We conclude that morphogenetic genes may participate differentially in the pathogenesis of UIP and NSIP-F. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Surg Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org RI Congregado, Miguel/B-9062-2009 OI Congregado, Miguel/0000-0002-2404-0176 FU NICHD NIH HHS [HD99-008] NR 35 TC 21 Z9 22 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 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD APR PY 2006 VL 80 IS 2 BP 119 EP 123 DI 10.1016/j.yexmp.2005.12.003 PG 5 WC Pathology SC Pathology GA 022IW UT WOS:000236049900002 PM 16448649 ER PT J AU Bonilha, VL Rayborn, ME Saotome, I McClatchey, AI Hollyfield, JG AF Bonilha, VL Rayborn, ME Saotome, I McClatchey, AI Hollyfield, JG TI Microvilli defects in retinas of ezrin knockout mice SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE retinal pigment epithelium; Muller cells; epithelium; microvilli; ezrin; microvilli-inclusions ID DEVELOPING MOUSE RETINA; PIGMENT-EPITHELIUM; INCLUSION DISEASE; APICAL MEMBRANE; ERM PROTEINS; TARGETED DISRUPTION; CELLS; TRANSPORTERS; CYTOSKELETON; EXPRESSION AB Ezrin, a member of the ezrin/moesin/radixin (ERM) family, localizes to microvilli of epithelia in vivo, where it functions as a bridge between actin filaments and plasma membrane proteins. In the eye, ezrin has been localized to both apical microvilli of Muller cells and retinal pigment epithelium (RPE) apical microvilli and basal infoldings. In the present study, we analyze these structures in the eyes of early postnatal ezrin knockout mice. This analysis indicates that the loss of ezrin leads to substantial reductions in the apical microvilli and basal infoldings in RPE cells and in the Muller cell apical microvilli. The absence of apical microvilli in the RPE is accompanied by the presence of microvilli-like, inclusions (MIs) in the RPE cytoplasm. Finally, photoreceptors in the ezrin knockout animals show substantial retardation in development as compared to their wild type littermates. (c) 2005 Elsevier Ltd. All rights reserved. C1 Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalmol Res, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Bonilha, VL (reprint author), Cleveland Clin Fdn, Cole Eye Inst, Dept Ophthalmol Res, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bonilhav@ccf.org FU NEI NIH HHS [EY06603, EY015638, EY014240] NR 42 TC 46 Z9 51 U1 0 U2 1 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 APR PY 2006 VL 82 IS 4 BP 720 EP 729 DI 10.1016/j.exer.2005.09.013 PG 10 WC Ophthalmology SC Ophthalmology GA 028TI UT WOS:000236511300021 PM 16289046 ER PT J AU Xie, ZC Tanzi, RE AF Xie, ZC Tanzi, RE TI Alzheimer's disease and post-operative cognitive dysfunction SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE Alzheimer's disease; postoperative cognitive dysfunction; beta-Amyloid Precursor Protein (APP); beta-Amyloid protein (A beta); anesthesia; apoptosis ID AMYLOID PRECURSOR PROTEIN; GAMMA-SECRETASE COMPLEX; INSULIN-DEGRADING ENZYME; PHOSPHOTYROSINE-BINDING DOMAIN; PERTURBED CALCIUM HOMEOSTASIS; PAIRED HELICAL FILAMENTS; LONG-TERM POTENTIATION; BETA-PROTEIN; INTRACELLULAR DOMAIN; IN-VIVO AB Alzheimer's disease (AD), an insidious and progressive neurodegenerative disorder accounting for the vast majority of dementia, is characterized by global cognitive decline and the robust accumulation of amyloid deposits and neurofibrillary tangles in the brain. This review article is based on the currently published literature regarding molecular studies of AD and the potential involvement of AD neuropathogenesis in post-operative cognitive dysfunction (POCD). Genetic evidence, confirmed by neuropathological and biochemical studies, indicates that excessive beta-amyloid protein (A beta) generated from amyloidogenic processing of the beta-amyloid precursor protein (APP) plays a fundamental role in the AD neuropathogenesis. A beta is produced from APP by P-secretase, and then gamma-secretase complex, consisting of presenilins, nicastrin (NCSTN), APH-1 and PEN-2. Additionally, A beta clearance and APP adaptor proteins can contribute to AD neuropathogenesis via affecting A beta levels. Finally, cellular apoptosis may also be involved in AD neuropathogenesis. Surgery and anesthesia can cause cognitive disorders, especially in elderly patients. Even the molecular mechanisms underlying these disorders are largely unknown; several perioperative factors such as hypoxia, hypocapnia and anesthetics may be associated with AD and render POCD via trigging AD neuropathogenesis. More studies to assess the potential relationship between anesthesia/surgery and AD dementia are, therefore, urgently needed. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, 114 16th St M3725, Charlestown, MA 02129 USA. EM zxie@partners.org FU NIA NIH HHS [P60 AG008812-15, K12 AG00294-17, AG 014713-07]; NIMH NIH HHS [MH 60009-03]; NINDS NIH HHS [K08 NS048140-01] NR 213 TC 86 Z9 116 U1 5 U2 30 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 2006 VL 41 IS 4 BP 346 EP 359 DI 10.1016/j.exger.2006.01.014 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 047OZ UT WOS:000237889900002 PM 16564662 ER PT J AU Molyneaux, BJ Arlotta, P Macklis, JD AF Molyneaux, BJ Arlotta, P Macklis, JD TI Molecular development and repair of corticospinal motor neuron circuitry SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 13th Annual Conference of the American-Society-for-Neural-Therapy-and-Repair CY APR 11-MAY 14, 2006 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 Harvard Univ, Massachusetts Gen Hosp, Dept Neurol & Neurosurg, Ctr Nervous Syst Repair, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Neurosci, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2006 VL 198 IS 2 BP 581 EP 582 DI 10.1016/j.expneurol.2006.02.074 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 033RJ UT WOS:000236866400088 ER PT J AU Haddad, R AF Haddad, R TI Current and future directions in the treatment of squamous cell carcinoma of the head and neck: multidisciplinary symposium on head and neck cancer SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Article DE epidermal growth factor receptor inhibitor; head and neck cancer; squamous cell carcinoma of the head and neck (SCCHN); tyrosine kinase inhibitor ID LOCALLY ADVANCED HEAD; PHASE-III; CONCOMITANT CHEMOTHERAPY; RADIATION-THERAPY; RADIOTHERAPY; CHEMORADIOTHERAPY; INTERGROUP; RECURRENT; TRIAL AB The treatment of head and neck cancer continues to represent a major challenge. Patients are typically treated with chemotherapy, radiation and surgery. Multiple resources are needed to allow patients to go through the treatment, and recovery can take months and often years. Those resources include, nutritionists, speech and swallow therapists, social workers, psychiatrists and dentists. It is of paramount importance that these patients have access to a multidisciplinary clinic that can best manage the problems that will invariably arise when treatment is started. These include mucositis, pain, xerostomia, swallowing dysfunction, depression, loss of work and severe deconditioning. Recent advances in the treatment of head and neck cancer have resulted in an improvement in survival. These advances have included the use of newer chemotherapeutic agents, better radiation planning and delivery and better surgical techniques. This report highlights some of the data presented in the first multidisciplinary symposium on head and neck cancer. Special attention is given to the use of newer 'targeted agents' and their incorporation in the definitive therapy with chemotherapy and radiation. Major focus is placed on epidermal growth factor inhibitors and their potential role both in the curative and recurrent settings. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Haddad, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. EM Robert_haddad@dfci.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD APR PY 2006 VL 10 IS 2 BP 333 EP 336 DI 10.1517/14728222.10.2.333 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 030OW UT WOS:000236645100013 PM 16548781 ER PT J AU Gupta, N Cohen, SA Bostrom, AG Kirschner, BS Baldassano, RN Winter, HS Ferry, GD Smith, T Abramson, O Gold, BD Heyman, MB AF Gupta, N Cohen, SA Bostrom, AG Kirschner, BS Baldassano, RN Winter, HS Ferry, GD Smith, T Abramson, O Gold, BD Heyman, MB TI Risk factors for initial surgery in pediatric patients with Crohn's disease SO GASTROENTEROLOGY LA English DT Article ID CHILDREN; ONSET; POPULATION; RECURRENCE; MORTALITY; ASCA AB Background & Aims: The cumulative incidence of surgery ranges from 40%-70% at 10 years from the time of diagnosis of Crohn's disease in adults. We retrospectively determined the cumulative incidence of and risk factors for surgery (intestinal resection) in pediatric patients with Crohn's disease. Methods: Uniform data from 989 consecutive Crohn's disease patients (age 0-17 years at diagnosis), collected from 6 different pediatric centers between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry, were analyzed. Results: Median follow-up time was 2.8 years (range, 1 day to 16.7 years). One hundred twenty-eight patients underwent surgery. Kaplan-Meier survival estimates of the cumulative incidence of surgery were 17% at 5 years and 28% at 10 years from the diagnosis of inflammatory bowel disease. Univariate Cox proportional hazards models showed leukocytosis (2.85 [hazard ratio]; P =.02), hypoalbuminemia (3.41; P =.05), and anti-Saccharomyces cerevisiae antibody (ASCA) positivity (3.43; P =.05) were associated with increased risk for surgery. Multivariate Cox models showed female gender (1.49; P =.03), initial diagnosis of ulcerative colitis (3.63; P <.0001), poor growth at presentation (2.16; P =.007), and abscess (1.90; P =.009), fistula (2.30; P =.0005), or stricture (3.41; P <.0001) development were associated with increased risk for surgery. Age 3-5 years (0.26; P =.01) or 6-12 years (0.62; P =.01) at diagnosis, fever at presentation (0.50; P =.03)7 and treatment with infliximab (0.36; P =.0005) or 5-aminosalicylic acid (0.44; P <.0001) were associated with decreased risk for surgery. Conclusion : Risk stratification during the course of Crohn's disease in pediatric patients will help to guide therapy that may improve the natural history of disease and decrease the need for surgery. C1 Univ Calif San Francisco, Childrens Hosp, San Francisco, CA 94143 USA. Childrens Healthcare Atlanta, Childrens Ctr Digest Healthcare, Atlanta, GA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. MassGen Hosp Children, Boston, MA USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Kaiser Permanente No Calif, Oakland, CA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Heyman, MB (reprint author), Univ Calif San Francisco, Childrens Hosp, 500 Parnassus Ave,MU-4 E,Room 403, San Francisco, CA 94143 USA. EM mheyman@peds.ucsf.edu FU NIDDK NIH HHS [DK006544, DK007762, DK53708, DK60617] NR 17 TC 83 Z9 86 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2006 VL 130 IS 4 BP 1069 EP 1077 DI 10.1053/j.gastro.2006.02.003 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 031ZG UT WOS:000236743100012 PM 16618401 ER PT J AU Terada, K Wakimoto, H Tyminski, E Chiocca, EA Saeki, Y AF Terada, K Wakimoto, H Tyminski, E Chiocca, EA Saeki, Y TI Development of a rapid method to generate multiple oncolytic HSV vectors and their in vivo evaluation using syngeneic mouse tumor models SO GENE THERAPY LA English DT Article DE BAC; herpes virus; oncolytic vector; Flp/FRT; Cre/loxP; luciferase ID HERPES-SIMPLEX-VIRUS; BACTERIAL ARTIFICIAL CHROMOSOME; ESCHERICHIA-COLI; BRAIN-TUMOR; ANTITUMOR IMMUNITY; AMPLICON VECTORS; PACKAGING SYSTEM; REPLICATION; EXPRESSION; TYPE-1 AB Replication-conditional herpes simplex virus (HSV)-based vectors have great potential in the treatment of various types of cancers including brain tumors. HSV mutants lacking the U(L)39 gene and both copies of the gamma(1)34.5 gene (e.g. MGH1, G207) have been demonstrated to possess oncolytic effects as well as potent anticancer vaccination effects without compromising safety. Such mutants thus provide optimal templates to produce novel oncolytic HSV vectors for cancer gene therapy applications. In order to accomplish quick and efficient construction of oncolytic HSV vectors, a novel BAC-based method designated as 'HSVQuik system' was developed. This system sequentially utilizes two different site-specific recombination systems to introduce virtually any transgene cassettes of interest into the deleted UL39 locus (Flp-FRT in Escherichia coli) and to release the vector genome sequence from the procaryotic plasmid backbone (Cre-loxP in Vero cells). Taking advantage of the HSVQuik system, we constructed three oncolytic HSV vectors that express mouse IL4, CD40 ligand and 6CK, respectively. In vivo therapeutic experiments using two luciferase-labeled syngeneic mouse brain tumor models revealed that expression of these immunomodulators significantly enhanced antitumor efficacy of oncolytic HSV. The HSVQuik system, together with luciferase-labeled tumor models, should expedite the process of generating and evaluating oncolytic HSV vectors for cancer gene therapy applications. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Charlestown, MA USA. RP Saeki, Y (reprint author), Ohio State Univ, Med Ctr, Dept Neurol Surg, Dardinger Lab Neurooncol & Neurosci, 385B Wiseman Hall,400 W 12th Ave, Columbus, OH 43210 USA. EM saeki.6@osu.edu FU NCI NIH HHS [P50 CA086355, P01 CA69246] NR 35 TC 51 Z9 53 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2006 VL 13 IS 8 BP 705 EP 714 DI 10.1038/sj.gt.3302717 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 029AR UT WOS:000236530700006 PM 16421599 ER PT J AU Yan, BS Kirby, A Shebzukhov, YV Daly, MJ Kramnik, I AF Yan, BS Kirby, A Shebzukhov, YV Daly, MJ Kramnik, I TI Genetic architecture of tuberculosis resistance in a mouse model of infection SO GENES AND IMMUNITY LA English DT Article DE tuberculosis; mouse; susceptibility; gene; QTL ID CELL-DEFICIENT MICE; HISTOCOMPATIBILITY COMPLEX HAPLOTYPE; VIRULENT MYCOBACTERIUM-TUBERCULOSIS; NATURAL-RESISTANCE; INTRACELLULAR INFECTIONS; SUSCEPTIBILITY; IMMUNITY; NRAMP1; BCG; STRAINS AB Tuberculosis remains a significant public health problem: one-third of the human population is infected with virulent Mycobacterium tuberculosis (MTB) and 10% of those are at risk of developing tuberculosis during their lifetime. In both humans and experimental animal models, genetic variation among infected individuals contributes to the outcome of infection. However, in immunocompetent individuals (the majority of patients), genetic determinants of susceptibility to tuberculosis remain largely unknown. Mouse models of MTB infection, allowing control of exposure and other potential environmental contributors, have proven extremely useful for examining this genetic component. In a cross of C3HeB/FeJ (susceptible) by C57BL/6J (resistant) inbred mouse strains, we have previously identified one major genetic locus, sst1, the susceptible allele of which did not confer an overt immunodeficiency, but rather specifically affected progression of lung tuberculosis. Having generated and tested the sst1 congenic strains, we have observed that this locus only partially explained the difference in susceptibility of the parental strains to MTB. We now present further studies controlling for the effect of the sst1, identify four additional tuberculosis susceptibility loci and characterize their effects by testing an independent cross, knockout or congenic mice. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Kramnik, I (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 665 Huntington Ave,Bldg 1,Room 909, Boston, MA 02115 USA. EM ikramnik@hsph.harvard.edu OI Kramnik, Igor/0000-0001-6511-9246; Yan, Bo-Shiun/0000-0002-9613-4788 FU NHLBI NIH HHS [R01 HL059836] NR 46 TC 32 Z9 33 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2006 VL 7 IS 3 BP 201 EP 210 DI 10.1038/sj.gene.6364288 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 036UB UT WOS:000237100100003 PM 16452998 ER PT J AU Sweet-Cordero, A Tseng, GC You, H Douglass, M Huey, B Albertson, D Jacks, T AF Sweet-Cordero, A Tseng, GC You, H Douglass, M Huey, B Albertson, D Jacks, T TI Comparison of gene expression and DNA copy number changes in a murine model of lung cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID CHROMOSOMAL INSTABILITY; BREAST-CANCER; ARRAY CGH; CARCINOGENESIS; AMPLIFICATION; DISCOVERY; ONCOGENE; TUMOR; MICE; CARCINOMAS AB Activation of oncogenic Kras in murine lung leads to the development of numerous small adenomas, only some of which progress over time to overt adenocarcinoma. Thus, although Kras is the initiating oncogene, it is likely that secondary genetic events are required for progression from adenoma to adenocarcinoma. Some of these secondary events may also be important in human lung adenocarcinoma. By comparing gene expression profiles with DNA copy number changes, we sought to identify genes that play key roles in tumor progression in this model. Gene expression profiling revealed significant heterogeneity among the tumor samples. In 27% of the tumors analyzed, whole- or subchromosome duplications or deletions in one or more chromosomes were seen. Recurrent duplications were seen on chromosomes 6, 8, 16, and 19, whereas chromosomes 4, 11, and 17 were frequently lost. Notably, focal amplifications or deletions were not seen. Despite the lack of focal amplication, we showed that chromosome duplication has a measurable effect on gene expression that is not uniform across the genome. We identified a group of genes whose gene expression was highly correlated with changes in DNA copy number. These highly correlated genes were enriched for gene ontology categories involved in the DNA damage response and telomere maintenance. C1 MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Childrens Hosp Boston, Dept Pediat Hematol & Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA USA. RP Jacks, T (reprint author), 40 Ames St,Bd E17-517, Cambridge, MA 02139 USA. EM tjacks@mit.edu NR 27 TC 28 Z9 28 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 2006 VL 45 IS 4 BP 338 EP 348 DI 10.1002/gcc.20296 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 018DG UT WOS:000235743400003 PM 16323170 ER PT J AU Hickey, AJ Chotkowski, HL Singh, N Ault, JG Korey, CA MacDonald, ME Glaser, RL AF Hickey, AJ Chotkowski, HL Singh, N Ault, JG Korey, CA MacDonald, ME Glaser, RL TI Palmitoyl-protein thioesterase 1 deficiency in Drosophila melanogaster causes accumulation of abnormal storage material and reduced life span SO GENETICS LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; TRANSMEMBRANE PROTEIN; BATTEN-DISEASE; INFANTILE TYPE; KNOCKOUT MICE; MUTANT MICE; MUTATIONS; VARIANT; EXPRESSION; NEURODEGENERATION AB Human neuronal ceroid lipofuscinoses (NCLs) are a group of genetic neurodegenerative diseases characterized by progressive death of neurons in the central nervous system (CNS) and accumulation of abnormal lysosomal storage material. Infantile NCL (INCL), the most severe form of NCL, is caused by mutations in the Ppt1 gene, which encodes the lysosomal enzyme palmitoyl-protein thioesterase I (ppt1). We generated mutations in the Ppt1 ortholog of Drosophila melanogaster to characterize phenotypes caused by Ppt1 deficiency in flies. Ppt1-deficient flies accumulate abnormal autofluorescent storage material predominantly in the adult CNS and have a life span 30% shorter than wild type, phenotypes that generally recapitulate disease-associated phenotypes common to all forms of NCL. In contrast, some phenotypes of Ppt1-deficient flies differed from those observed in human INCL. Storage material in flies appeared as highly laminar spherical deposits in cells of the brain and as curvilinear profiles in cells of the thoracic ganglion. This contrasts with the granular deposits characteristic of human INCL. In addition, the reduced life span of Ppt1-deficient flies is not caused by progressive death of CNS neurons. No changes in brain morphology or increases in apoptotic cell death of CNS neurons were detected in Ppt1-deficient flies, even at advanced ages. Thus, Ppt1-deficient flies accumulate abnormal storage material and have a shortened life span without evidence of concomitant neurodegeneration. C1 New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. SUNY Albany, Dept Biomed Sci, Albany, NY 12201 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Glaser, RL (reprint author), New York State Dept Hlth, Wadsworth Ctr Labs & Res, POB 22002, Albany, NY 12201 USA. EM glaser@wadsworth.org FU NINDS NIH HHS [NS33648, NS44572, R01 NS033648, R21 NS044572] NR 60 TC 21 Z9 22 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2006 VL 172 IS 4 BP 2379 EP 2390 DI 10.1534/genetics.105.053306 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 038ML UT WOS:000237225800030 PM 16452138 ER PT J AU Sands, BE AF Sands, BE TI Immunosuppressive drugs in ulcerative colitis: twisting facts to suit theories? SO GUT LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INFLAMMATORY-BOWEL-DISEASE; INTRAVENOUS CYCLOSPORINE; CROHNS-DISEASE; DOUBLE-BLIND; AZATHIOPRINE THERAPY; FINAL REPORT; 6-MERCAPTOPURINE; METHOTREXATE; MAINTENANCE AB Immunosuppressive drugs have become a mainstay of therapy for the inflammatory bowel diseases. Although robust evidence exists in support of the use of these drugs in Crohn's disease, a close evaluation of the available data in ulcerative colitis reveals a much weaker evidence base. In particular, randomised controlled trials of azathioprine, the most commonly used immunosuppressive agent, do not provide rich evidence of efficacy whereas observational cohorts suggest this agent is effective, particularly in patients with relapsing disease who require corticosteroids. Ciclosporin is also effective in the most refractory cases but its efficacy needs to be carefully weighed against the possibility of rare but life threatening complications. Although the evidence base in support of immunosuppressive drugs in ulcerative colitis is not as strong as in Crohn's disease, these agents clearly have a role in the treatment of this disease. C1 Massachusetts Gen Hosp, Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 33 TC 22 Z9 24 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2006 VL 55 IS 4 BP 437 EP 441 DI 10.1136/gut.2005.078055 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 029KT UT WOS:000236561900002 PM 16531519 ER PT J AU Sandborn, W Sands, B Hanauer, S Bloomfeld, R AF Sandborn, W Sands, B Hanauer, S Bloomfeld, R TI The effectiveness of continuing the induction dose of Asacol into the maintenance phase: Results from the community setting SO GUT LA English DT Meeting Abstract CT Annual Meeting of the British-Society-of-Gastroenterology CY MAR 20-23, 2006 CL Birmingham, ENGLAND SP British Soc Gastroenterol C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Div Gastroenterol & Hepatol, Chicago, IL 60637 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2006 VL 55 SU 2 MA 311 BP A81 EP A82 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 020PN UT WOS:000235922100308 ER PT J AU Seiden, MV Gordon, AN Bodurka, DC Matulonis, UA Penson, RT Reed, E Alberts, DS Weems, G Cullen, M McGuire, WP AF Seiden, MV Gordon, AN Bodurka, DC Matulonis, UA Penson, RT Reed, E Alberts, DS Weems, G Cullen, M McGuire, WP TI A phase II study of irofulven in women with recurrent and heavily pretreated ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; MGI-114; irofulven; visual toxicity; phase II trial; recurrent disease ID PEGYLATED LIPOSOMAL DOXORUBICIN; LUNG-CARCINOMA XENOGRAFT; TRADITIONAL ANTICANCER AGENTS; GYNECOLOGIC-ONCOLOGY-GROUP; 6-HYDROXYMETHYLACYLFULVENE MGI-114; TOPOTECAN; EFFICACY; TRIAL; HMAF; CHEMOTHERAPY AB Objective. To determine the safety and efficacy of a novel illudin S derivative, irofulven (MG1-114), in patients with recurrent ovarian cancer who had received extensive prior chemotherapy. Methods. The trial was an open label phase II study. Patients initially enrolled in this study were treated every 14 days with a dose of 24 mg/ m(2). Unexpected retinal toxicity associated with this dose and schedule lead to modification of the dosing to 0.55 mg/kg on the same schedule with a maximum individual dose of 50 mg. Dose reductions were permitted based on both hematologic and non-hematologic toxicities. Results. Seventy-four women were accrued and stratified into two cohorts including 58 women with platinum-resistant disease and 16 with platinum-sensitive disease. Non-hematologic toxicities included nausea, vomiting, and fatigue. Thirty-one women had between one and six visual symptoms, most were Grade 1 and 2 in nature. The majority of visual toxicities resolved either during treatment or post-treatment with irofulven. There was one partial response in each cohort with 19 (33%) and 8 (50%) of women having stable disease in the platinum-resistant and platinum-sensitive cohorts, respectively. Conclusions. Irofulven at 24 rng/m(2) on every 14-day schedule is associated with significant retinal toxicity in this patient population. Dosing at 0.55 mg/kg has persistent retinal toxicity, yet demonstrated only limited anti-tumor activity in a population of women who had received extensive prior chemotherapy. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Partners Canc Care Program, Gynecol Oncol Res Program, Boston, MA 02115 USA. Univ Arizona, Ctr Canc, Tucson, AZ 85721 USA. Univ Texas, MD Anderson Canc Ctr, Austin, TX 78712 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. CDC, Atlanta, GA 30309 USA. MGI PHARMA INC, Bloomington, MN USA. Franklin Sq Hosp, Baltimore, MD 21237 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM mseiden@partners.org NR 28 TC 22 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2006 VL 101 IS 1 BP 55 EP 61 DI 10.1016/j.ygyno.2005.09.036 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 028KN UT WOS:000236486400009 PM 16260029 ER PT J AU Canada, AL Parker, PA de Moor, JS Basen-Engquist, K Ramondetta, LM Cohen, L AF Canada, AL Parker, PA de Moor, JS Basen-Engquist, K Ramondetta, LM Cohen, L TI Active coping mediates the association between religion/spirituality and quality of life in ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article ID BREAST-CANCER; PSYCHOLOGICAL ADJUSTMENT; FUNCTIONAL ASSESSMENT; SPIRITUAL BELIEFS; OLDER-ADULTS; WOMEN; RELIGION; HEALTH; ADAPTATION; DEPRESSION AB Objectives. This study investigated the role of religion/spirituality (R/S) and coping in quality of life (QOL) in 129 women immediately prior to a course of adjuvant chemotherapy for ovarian cancer. Methods. Participants completed the COPE, the Functional Assessment of Cancer Therapy-Ovarian (FACT-O), and the Systems of Belief Inventory-15R (SBI-15R). Women averaged 58.9 years of age (SD = 11.5) and were primarily Caucasian (86%), married (74%), and had received at least some college education (67%). Eighty-five percent of the participants had stage III or IV ovarian cancer at study entry. Results. Correlational analyses revealed that R/S was associated with active coping (r = 0.23, P = 0.022), overall QOL (r = 0.25, P = 0.012), emotional and functional well-being (r = 0.24, P = 0.014 and r = 0.28, P = 0.004), and fewer ovarian cancer-specific concerns (r = 0.27, P = 0.006). In addition, active coping was related to overall QOL (r = 0.22, P = 0.029) and social and functional well-being (r = 0.20, P = 0.042 and r = 0.33, P = 0.001). Tests of mediation between these variables suggested that the positive associations between R/S and functional well-being and R/S and overall QOL were mediated through the use of active coping. Conclusion. Future studies are needed to better understand the complex relationships between R/S, coping, and QOL throughout the ovarian cancer treatment experience. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, Houston, TX 77230 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Unit 1330, Houston, TX 77230 USA. Univ Texas, MD Anderson Canc Ctr, Unit 008, Houston, TX 77030 USA. RP Canada, AL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, POB 310439, Houston, TX 77230 USA. EM alcanada@mdanderson.org NR 40 TC 33 Z9 34 U1 1 U2 7 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 APR PY 2006 VL 101 IS 1 BP 102 EP 107 DI 10.1016/j.ygyno.2005.09.045 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 028KN UT WOS:000236486400017 PM 16256181 ER PT J AU Evans, DC Nichol, WP Perlin, JB AF Evans, Dwight C. Nichol, W. Paul Perlin, Jonathan B. TI Effect of the implementation of an enterprise-wide Electronic Health Record on productivity in the Veterans Health Administration SO HEALTH ECONOMICS POLICY AND LAW LA English DT Article AB Since 1995, the Veterans Health Administration (VHA) has had an ongoing process of systems improvement that has led to dramatic improvement in the quality of care delivered. A major component of the redesign of the VHA has been the creation of a fully developed enterprise-wide Electronic Health Record (EHR). VHA's Health Information Technology was developed in a collaborative fashion between local clinical champions and central software engineers. Successful national EHR implementation was achieved by 1999, since when the VHA has been able to increase its productivity by nearly 6 per cent per year. C1 [Perlin, Jonathan B.] Vet Hlth Adm, Washington, DC 20240 USA. [Nichol, W. Paul] Univ Washington, Sch Med, Seattle, WA USA. [Nichol, W. Paul] VA Puget Sound HCS, Seattle, WA USA. [Evans, Dwight C.] VA Loma Linda HCS, Loma Linda, CA USA. [Evans, Dwight C.] Loma Linda Univ, Sch Med, Loma Linda, CA USA. RP Perlin, JB (reprint author), Vet Hlth Adm, 810 Vermont St, Washington, DC 20240 USA. EM jonathan.perlin@va.gov NR 15 TC 52 Z9 52 U1 2 U2 6 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 1744-1331 J9 HEALTH ECON POLICY L JI Health Econ. Policy Law PD APR PY 2006 VL 1 IS 2 BP 163 EP 169 DI 10.1017/S1744133105001210 PG 7 WC Health Policy & Services SC Health Care Sciences & Services GA V18XW UT WOS:000208038500005 PM 18634688 ER PT J AU Harthorne, JW AF Harthorne, JW TI Seymour Furman, MD - 7-12-1931-2-20-2006 SO HEART RHYTHM LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Yawkey Ctr 5, Boston, MA 02114 USA. RP Harthorne, JW (reprint author), Massachusetts Gen Hosp, Yawkey Ctr 5, Fl 5A, Boston, MA 02114 USA. EM Harthorne.John@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD APR PY 2006 VL 3 IS 4 BP 498 EP 499 DI 10.1016/j.hrthm.2006.03.006 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 031ZJ UT WOS:000236743400027 PM 16567307 ER PT J AU Nugalieva, ZZ Opekun, AR Graham, DY AF Nugalieva, ZZ Opekun, AR Graham, DY TI Problem of distinguishing false-positive tests from acute or transient Helicobacter pylori infections SO HELICOBACTER LA English DT Article DE Helicobacter pylori; acute infection; transient infection; pepsinogens; predictive values; urea breath test ID SERUM PEPSINOGEN-I; TERM FOLLOW-UP; ERADICATION THERAPY; CHILDREN; GASTRITIS; TRANSMISSION; POPULATION; PREVALENCE; COMMUNITY; ULCER AB Background: Reliable detection of acute Helicobacter pylori infections remains problematic. The high prevalence of false-positive non-invasive tests in low H. pylori prevalence populations makes identification of acute and transient infections difficult. Methods: We explored the use of serum pepsinogens (PG) for diagnosis of acute infection in patients following H. pylori challenge such that the onset of the infection was known. We then compared those findings to a group of children with presumed acute infections defined as a positive urea breath test (UBT) and negative IgG serology. Results: We examined the pattern and calculated cut-off values of PG levels in 18 adult volunteers with known acute H. pylori infection. We then compared the results with sera from nine symptomatic children with presumed acute H. pylori infection and a matched control group of nine children who did not meet criteria for acute H. pylori infection. In acute infection, both PGI and II levels increased following H. pylori infection reaching a peak by 2 weeks post-infection. The frequency of a positive test defined as a value > mean +2 SD was 17, 71, and 94% at week 1, 2, and 4 post-infection, respectively. Only one child with presumed acute H. pylori infection had an elevated serum PGI and one had an elevated PGII. Five of the children had follow-up UBTs and four were negative consistent with the diagnosis of false-positive UBT. H. pylori infection was confirmed in the child with an elevated PGI level. Conclusions: These data suggest that a single positive noninvasive test in populations of low prevalence is most likely a false-positive result. This suggests that a single positive test requires confirmation preferably using a test that measures a different parameter (e.g., UBT confirmed by stool antigen test). It appears that most "transient"H. pylori infections are diagnosed on the basis of false-positive tests. PG levels are possible candidates as the confirmatory test. C1 Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Dept Pediat, Houston, TX 77030 USA. Vet Affairs Med Ctr, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, RM 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu NR 42 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD APR PY 2006 VL 11 IS 2 BP 69 EP 74 DI 10.1111/j.1523-5378.2006.00380.x PG 6 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 020EX UT WOS:000235892300001 ER PT J AU Bellon, JR Katz, A Taghian, A AF Bellon, JR Katz, A Taghian, A TI Radiation therapy for breast cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID INITIAL CLINICAL-EXPERIENCE; COMBINED-MODALITY TREATMENT; EXTERNAL-BEAM RADIOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; SURGICAL ADJUVANT BREAST; 20-YEAR FOLLOW-UP; CELL LUNG-CANCER; EARLY-STAGE; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY AB Over the past 5 decades, radiotherapy (RT) has become an integral part la I of the combined modality management of breast cancer. Although its effect on local control has been long demonstrated, only recently has adjuvant RT been shown to have a significant effect on breast cancer mortality [1] and overall survival (OS) [2]. With a better understanding of the parameters predicting for local failure, such as tumor margins, die success rate of lumpectomy and breast radiation has reached more than 95% at 10 years [3]. Furthermore, substantial progress in RT technology, particularly the advent of CT-guided simulation and three-dimensional conformal planning, may reduce the potential complications from radiation [4-6] and has Oven the radiation oncologist the ability to target precisely the affected quadrant of the breast, resulting in the investigation of partial-breast irradiation (PBI) techniques. This article summarizes the adjuvant role of RT after mastectomy and lumpectomy, as well as the rationale and techniques for PBI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. RP Taghian, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 32 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org FU NCI NIH HHS [P50 CA89393] NR 93 TC 5 Z9 5 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2006 VL 20 IS 2 BP 239 EP + DI 10.1016/j.hoc.2006.01.014 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 054GQ UT WOS:000238365200002 PM 16730294 ER PT J AU Nedea, EA DeLaney, TF AF Nedea, EA DeLaney, TF TI Sarcoma and skin radiation oncology SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID SOFT-TISSUE SARCOMA; PRIMITIVE NEUROECTODERMAL TUMORS; TERM-FOLLOW-UP; FAMILIAL ADENOMATOUS POLYPOSIS; METASTATIC MALIGNANT-MELANOMA; COOPERATIVE EWINGS-SARCOMA; NONCYTOTOXIC DRUG-THERAPY; OSTEOSARCOMA STUDY-GROUP; SQUAMOUS-CELL CARCINOMA; HIGH-GRADE OSTEOSARCOMA AB Sarcomas are malignant tumors that arise from skeletal and extraskeletal connective tissues, including the peripheral nervous system. Although ectodermal in origin, the malignant tumors of the peripheral nerves are included because of the similarities in clinical behavior, management, and outcome. Sarcomas are rare, with an estimated incidence in the United States of approximately 11,120 cases diagnosed annually, representing about 0.80% of the 1,368,030 new malignant tumors [1]. Approximately 76% of sarcomas arise in soft tissue; the remainder occurs in bone [2]. Because of the rarity and gravity of these tumors, one might predict a clinical advantage for evaluation and management in a center with a team of dedicated subspecialists including clinicians in surgical, orthopedic, medical, pediatric, and radiation oncology. The gain in outcome provided by this multidisciplinary expertise was illustrated in one study that examined the outcome for 375 patients with soft tissue sarcoma of the extremities and torso according to the time of referral to a tumor center in the South Sweden Health Care Region [3]. When compared with patients referred preoperatively, local recurrence rates were increased in patients not referred at any time (2.4 times higher) and in patients referred after surgery (1.3 times higher). C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM tdeloney@partners.org NR 152 TC 20 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2006 VL 20 IS 2 BP 401 EP + DI 10.1016/j.hoc.2006.01.017 PG 30 WC Oncology; Hematology SC Oncology; Hematology GA 054GQ UT WOS:000238365200008 PM 16730300 ER PT J AU Truong, MT AF Truong, MT TI Current role of radiation therapy in the management of malignant brain tumors SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID LOW-GRADE GLIOMA; RECURSIVE PARTITIONING ANALYSIS; MEDICAL-RESEARCH-COUNCIL; RADIOTHERAPY PLUS BCNU; RANDOMIZED-TRIAL; GLIOBLASTOMA-MULTIFORME; ONCOLOGY-GROUP; STEREOTACTIC RADIOSURGERY; CLINICAL-TRIAL; POSTOPERATIVE RADIOTHERAPY AB Malignant brain tumors include a heterogeneous group of neoplasms encompassing both primary brain tumors (arising from malignant transformation of tissue elements of the central nervous system) and systemic malignancy metastasizing to the brain. Primary malignant brain tumors represent about 1.35% of all primary malignant cancers and occur with an incidence of 18,820 new cases in the United States in 2006. They accounted for 12,820 deaths in the United States according to the 2006 American Cancer Society Statistics [1]. Brain metastases are significantly more common, with an annual incidence of 170,000 people in the United States [2]. Clinical presentation of brain tumors can vary depending on the location of the lesion, die rate of tumor growth, and histologic type. The World Health Organization (WHO) classification of primary brain tumors categorizes 12 main groups of approximately 100 distinct pathologic entities [3]. For the purposes of treatment management, primary brain gliomas are broadly classified into low-grade (WHO grade I and II) and high-grade gliomas, anaplastic astrocytoma (WHO grade III), and glioblastoma multiforme (WHO grade IV). Malignant gliomas account for about 40% of primary brain tumors, and approximately half of these are glioblastoma multiforme, based on data from the Central Brain Tumor Registry of the United States [4]. Primary brain malignancies tend to spread locally, infiltrating the adjacent brain parenchyma, potentially causing edema and mass effect. Spread outside the central nervous system is rare. Certain primary brain tumors, including medulloblastoma and primary central nervous system lymphoma, may spread to the cerebral spinal fluid. Brain metastases arise from hematogenous spread, usually depositing tumor cells at the gray matter-white matter junction of the brain. Lesions are often discrete spherical lesions that shift the normal brain tissue rather than infiltrate it. Hemorrhage into the lesion can often be found, particularly with melanoma and renal cell carcinoma. Malignant brain tumors present a therapeutic challenge to the oncologist that requires multidisciplinary coordination between the neurosurgeon, radiation oncologist, neuro-oncologist, neuroradiologist, neurologist, and rehabilitation specialists. Treatment is dictated by the tumor location, histology, and patient factors such as age and performance status. C1 Boston Univ, Sch Med, Dept Radiat Oncol, Boston Med Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Truong, MT (reprint author), Boston Univ, Sch Med, Dept Radiat Oncol, Boston Med Ctr, EB 11,88 E Newton St, Boston, MA 02118 USA. EM mttruong@partners.org NR 88 TC 4 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2006 VL 20 IS 2 BP 431 EP + DI 10.1016/j.hoc.2006.01.022 PG 24 WC Oncology; Hematology SC Oncology; Hematology GA 054GQ UT WOS:000238365200009 PM 16730301 ER PT J AU Gibbs, IC Tuamokumo, N Yock, TI AF Gibbs, IC Tuamokumo, N Yock, TI TI Role of radiation therapy in pediatric cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NATIONAL-WILMS-TUMOR; CHILDRENS ONCOLOGY GROUP; LONG-TERM SURVIVORS; IV-S NEUROBLASTOMA; EWINGS-SARCOMA; INTERGROUP RHABDOMYOSARCOMA; PROGNOSTIC-FACTORS; HODGKINS-DISEASE; CHILDHOOD RHABDOMYOSARCOMA AB Although the incidence of childhood cancer has stabilized over the past few years, approximately 12,000 new cases are diagnosed each year in the United States among patients who are 19 years or younger [1,2]. Common childhood cancers include leukemia, lymphoma, central nervous system (CNS) tumors, neuroblastoma, Wilms' tumor, and sarcomas [3]. There have been statistically significant differences in the 5-year survival rates for childhood cancer between the periods of 1974 to 1976 and 1992 to 1999, which are 56% and 78%, respectively [4]. Die overall increase in the survival rate for childhood cancer has been attributed to advances in chemotherapeutic agents, refinements in bone marrow transplantation, Improvements in surgical and radiotherapy techniques, and the centralization of care through cooperative oncology groups. In the United States, it is estimated that approxmiately 90% of childhood cancers are treated by a Children's Oncology Group (COG) affiliated institution [5]. The treatment of childhood cancer is often regarded as one of the great successes of contemporary medicine. Radiotherapy has had an important role in the treatment and cure of childhood tumors. Unfortunately, it has also been associated with adverse late effects on growth and development, endocrine function, gastrointestinal dysfunction, musculoskeletal and integumentary hypoplasia, cardiac dysfunction, endocrine effects, and second malignancies [6]. The most challenging issue in radiotherapy for childhood tumors is minimizing the late effects of therapy among survivors. The current role of radiotherapy in management of the most common childhood malignancies as well as new approaches and technologies addressing the issue of late effects are discussed herein. C1 Stanford Univ, Dept Radiat Oncol, Stanford Canc Ctr, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA. RP Gibbs, IC (reprint author), Stanford Univ, Dept Radiat Oncol, Stanford Canc Ctr, Sch Med, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM iris.gibbs@stanford.edu NR 80 TC 18 Z9 19 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2006 VL 20 IS 2 BP 455 EP + DI 10.1016/j.hoc.2006.01.015 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 054GQ UT WOS:000238365200010 PM 16730302 ER PT J AU Robertson, NG Cremers, CWRJ Huygen, PLM Ikezono, T Krastins, B Kremer, H Kuo, SF Liberman, MC Merchant, SN Miller, CE Nadol, JB Sarracino, DA Verhagen, WIM Morton, CC AF Robertson, NG Cremers, CWRJ Huygen, PLM Ikezono, T Krastins, B Kremer, H Kuo, SF Liberman, MC Merchant, SN Miller, CE Nadol, JB Sarracino, DA Verhagen, WIM Morton, CC TI Cochlin immunostaining of inner ear pathologic deposits and proteomic analysis in DFNA9 deafness and vestibular dysfunction SO HUMAN MOLECULAR GENETICS LA English DT Article ID SENSORINEURAL HEARING-LOSS; TEMPORAL BONE FINDINGS; MENIERES-DISEASE; COCHLEOVESTIBULAR DYSFUNCTION; EXTRACELLULAR-MATRIX; TRABECULAR MESHWORK; MUTATION DFNA9; BELGIAN FAMILY; MESSENGER-RNA; LCCL DOMAIN AB Seven missense mutations and one in-frame deletion mutation have been reported in the coagulation factor C homology (COCH) gene, causing the adult-onset, progressive sensorineural hearing loss and vestibular disorder at the DFNA9 locus. Prevalence of COCH mutations worldwide is unknown, as there is no systematic screening effort for late-onset hearing disorders; however, to date, COCH mutations have been found on four continents and the possibility of COCH playing an important role in presbycusis and disorders of imbalance has been considered. Cochlin (encoded by COCH) has also been shown as a major target antigen for autoimmune sensorineural hearing loss. In this report, we present histopathology, immunohistochemistry and proteomic analyses of inner ear tissues from post-mortem DFNA9 temporal bone samples of an individual from a large Dutch kindred segregating the P51S mutation and adult human unaffected controls, and wild-type (+/+) and Coch null (-/-) knock-out mice. DFNA9 is an inner ear disorder with a unique histopathology showing loss of cellularity and aggregation of abundant homogeneous acellular eosinophilic deposits in the cochlear and vestibular labyrinths, similar to protein aggregation in well-known neurodegenerative disorders. By immunohistochemistry on the DFNA9 temporal bone sections, we have shown cochlin staining of the characteristic cochlear and vestibular deposits, indicating aggregation of cochlin in the same structures in which it is normally expressed. Proteomic analysis identified cochlin as the most abundant protein in mouse and human cochleae. The high-level expression and stability of cochlin in the inner ear, even in the absence and severe atrophy of the fibrocytes that normally express COCH, are shown through these studies and further elucidate the pathobiologic events occurring in DFNA9 leading to hearing loss and vestibular dysfunction. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. Radboud Univ Med Ctr, Dept Otorhinolaryngol, Nijmegen, Netherlands. Nippon Med Coll, Dept Otorhinolaryngol, Tokyo 113, Japan. Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab,Dept Otol & Laryngol, Boston, MA USA. Canisius Wilhelmina Hosp, Dept Neurol, Nijmegen, Netherlands. RP Morton, CC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet, 77 Ave Louis Pasteur,NRB 160, Boston, MA 02115 USA. EM cmorton@partners.org RI Kremer, Hannie/F-5126-2010; Cremers, C.W.R.J./L-4254-2015; Huygen, P.L.M./L-4401-2015 OI Kremer, Hannie/0000-0002-0841-8693; FU NIDCD NIH HHS [R01 DC000188, R01 DC000188-27, R01-DC0188, R01-DC03402]; PHS HHS [P30-05209] NR 56 TC 51 Z9 53 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR 1 PY 2006 VL 15 IS 7 BP 1071 EP 1085 DI 10.1093/hmg/ddl022 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 023DO UT WOS:000236105800003 PM 16481359 ER PT J AU Kyo, S Sakaguchi, J Ohno, S Mizurnoto, Y Maida, Y Hashimoto, M Nakamura, M Takakura, M Nakajima, M Masutomi, K Inoue, M AF Kyo, S Sakaguchi, J Ohno, S Mizurnoto, Y Maida, Y Hashimoto, M Nakamura, M Takakura, M Nakajima, M Masutomi, K Inoue, M TI High twist expression is involved in infiltrative endometrial cancer and affects patient survival SO HUMAN PATHOLOGY LA English DT Article DE twist; endometrial cancer; EMT; survival; E-cadherin ID E-CADHERIN EXPRESSION; PROSTATE-CANCER; CARCINOMA; BREAST; GENE; METHYLATION; METASTASIS; INVASION; CELLS; LUNG AB Epithelial-mesenchymal transition (EMT) is critical not only for morphogenesis during embryonic development but also the conversion of early-stage tumors into infiltrative phenotypes. The present study examines the expression of Twist, a highly conserved bHLH transcription factor that is known to promote EMT, and evaluated its prognostic significance in endometrial cancers. Tissue specimens from 70 patients with endometrial cancer who underwent primary surgery were immunohistochemically evaluated for Twist expression. A semi quantitative scoring system was developed based on the intensity and extent of cancer cells with Twist expression. Thirty-six patients (51%) exhibited high Twist expression and 34 (49%) had low expression. Most cases exhibited both cytoplasmic and nuclear staining mainly observed in cancer foci and, preferentially, at the margin but, in some cases, the stromal cells located adjacent to cancer foci as well. Among various clinical variables, high Twist expression was significantly associated with deep myometrial invasion (> 1/2) (P = .012) and concurrent with decreased E-cadherin expression (P < .001), a hallmark of EMT. In univariate survival analyses, both myometrial invasion and Twist expression influenced overall survival, but Cox multivariate analyses revealed that only Twist was an independent predictor of patient survival (hazard ratio, 5.12; P = .023). Thus, our data implies that high Twist expression is a potential novel prognostic factor for disease survival of endometrial cancer. Furthermore, the present study implicates Twist as a potential therapeutic target for this tumor type. (c) 2006 Elsevier Inc. All rights reserved. C1 Kanazawa Univ, Dept Obstet & Gynecol, Grad Sch Med Sci, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Dept Drug Metab & Toxicol, Div Pharmaceut Sci, Grad Sch Med Sci, Kanazawa, Ishikawa 9201192, Japan. Dana Farber Canc Inst, Dept Med Oncol & Biostat Sci, Boston, MA 02115 USA. RP Kyo, S (reprint author), Kanazawa Univ, Dept Obstet, Ishokawa 9208641, Japan. EM satoruky@med.kawazawa-u.ac.jp RI Takakura, Masahiro/E-1080-2011; Nakajima, Miki/C-3990-2015 NR 21 TC 99 Z9 110 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD APR PY 2006 VL 37 IS 4 BP 431 EP 438 DI 10.1016/j.humpath.2005.12.021 PG 8 WC Pathology SC Pathology GA 031TR UT WOS:000236727500007 PM 16564917 ER PT J AU Kumar, PA Pitteloud, N Andrews, PAM Dwyer, A Hayes, F Crowley, WF Dym, M AF Kumar, PA Pitteloud, N Andrews, PAM Dwyer, A Hayes, F Crowley, WF Dym, M TI Testis morphology in patients with idiopathic hypogonadotropic hypogonadism SO HUMAN REPRODUCTION LA English DT Article DE hormonal therapy; idiopathic hypogonadotropic hypogonadism; Sertoli cells; spermatogonia; testis ID GONADOTROPIN-RELEASING HORMONE; MONKEY MACACA-MULATTA; SEMINIFEROUS EPITHELIUM; GERM-CELLS; MEN; PUBERTY; SPERMATOGENESIS; ULTRASTRUCTURE; PROLIFERATION; SPERMATOGONIA AB BACKGROUND: Adult patients with idiopathic hypogonadotropic hypogonadism (IHH) typically present with absent puberty and therefore have prepubertal testes. IHH is recognized as one of the few curable causes of male infertility and is often effectively treated with either gonadotropins or pulsatile GnRH therapy. The objective of this study was to determine the structure of the testis prior to initiation of treatment. METHODS AND RESULTS: Eight adult IHH patients with prepubertal testes (< 4 ml), with no previous gonadotropin therapy and with no history of cryptorchidism underwent open bilateral testicular biopsy prior to the initiation of hormonal treatment. The testes of all patients showed seminiferous cords separated by interstitium composed of blood vessels, connective tissue cells and collagen fibres but typical adult Leydig cells were absent. The cords contained only Sertoli cells and early type A spermatogonia. The spermatogonia mostly resided in the centre of the cords and were often large, typical of gonocytes. Sertoli cells appeared immature with ovoid nuclei devoid of infoldings and cytoplasm that lacked polarity. Tight junctional complexes commonly found connecting adult Sertoli cells were lacking. CONCLUSIONS: These results demonstrate that the immature testes from patients with the severe form of IHH possess early spermatogonia that could possibly reinitiate spermatogenesis with appropriate hormone stimulation. Therefore, the immature testis of this IHH subset resembles those of prepubertal boys and may provide important biologic and genetic insights into testicular development. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20057 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Reprod Endocrine Sci Ctr, Boston, MA USA. RP Georgetown Univ, Med Ctr, Dept Cell Biol, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM dymm@georgetown.edu RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NICHD NIH HHS [HD 15788, HD 33728, R01 HD015788, U54 HD028138] NR 29 TC 9 Z9 9 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 APR PY 2006 VL 21 IS 4 BP 1033 EP 1040 DI 10.1093/humrep/dei444 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 025GN UT WOS:000236253500030 PM 16396935 ER PT J AU Karayiannis, NB Mukherjee, A Glover, JR Ktonas, PY Frost, JD Hrachovy, RA Mizrahi, EA AF Karayiannis, NB Mukherjee, A Glover, JR Ktonas, PY Frost, JD Hrachovy, RA Mizrahi, EA TI Detection of pseudo sinusoidal epileptic seizure segments in the neonatal EEG by cascading a rule-based algorithm with a neural network SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE electroencephalography; epileptic seizure segment; feedforward neural network (FFNN); neonatal seizure; quantum neural network (QNN) ID NEWBORN EEG; INFANTS AB This paper presents an approach to detect epileptic seizure segments in the neonatal electroencephalogram (EEG) by characterizing the spectral features of the EEG waveform using a rule-based algorithm cascaded with a neural network. A rule-based algorithm screens out short segments of pseudosinusoidal EEG patterns as epileptic based on features in the power spectrum. The output of the rule-based algorithm is used to train and compare the performance of conventional feedforward neural networks and quantum neural networks. The results indicate that the trained neural networks, cascaded with the rule-based algorithm, improved the performance of the rule-based algorithm acting by itself. The evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal seizure segments reveals its potential as a building block of the automated seizure detection system under development. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. Baylor Coll Med, Peter Kellaway Sect Neurophysiol, Dept Neurol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Karayiannis, NB (reprint author), Univ Houston, Dept Elect & Comp Engn, N308 Engn Bldg 1, Houston, TX 77204 USA. EM karayiannis@uh.edu FU NINDS NIH HHS [1 R01 NS040577, N01-NS-2316] NR 27 TC 24 Z9 24 U1 1 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD APR PY 2006 VL 53 IS 4 BP 633 EP 641 DI 10.1109/TBME.2006.870249 PG 9 WC Engineering, Biomedical SC Engineering GA 029IY UT WOS:000236557100007 PM 16602569 ER PT J AU Obrosky, DS Edick, SM Fine, MJ AF Obrosky, DS Edick, SM Fine, MJ TI The emergency department triage of community-acquired pneumonia project data and documentation systems: A model for multicenter clinical trials SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE clinical trials; data dictionary; data management systems; documentation; quality assurance AB Multicenter clinical trials are complex undertakings that require significant resources to ensure efficient, high quality research. This paper describes the goals, design, and implementation of a multicenter clinical trial database management system to support this aim. A large number of study sites or patients, and the goal of automatically generating large portions of data management infrastructure from common metadata, motivated the development of the system. This paper also describes extensions for a generalized project documentation system, and discusses plans for further extensions and improvements based on observed strengths, limitations, and anticipated technological change. C1 Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15240 USA. VA Healthcare Syst, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Off Res & Dev, Pittsburgh, PA 15206 USA. RP Obrosky, DS (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15240 USA. EM obroskyds@msx.upmc.edu; Stacey.Edick@va.gov; Michael.Fine@va.gov FU AHRQ HHS [R01-HS10049] NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD APR PY 2006 VL 10 IS 2 BP 377 EP 384 DI 10.1109/TITB.2005.864369 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 030ZR UT WOS:000236674400018 PM 16617626 ER PT J AU Ward, V Hennig, BJ Hirai, K Tahara, H Tamori, A Dawes, R Saito, M Bangham, C Stephens, H Goldfeld, AE Kunachiwa, W Leetrakool, N Hopkin, J Dunstan, S Hill, A Bodmer, W Beverley, PC Tchilian, EZ AF Ward, V Hennig, BJ Hirai, K Tahara, H Tamori, A Dawes, R Saito, M Bangham, C Stephens, H Goldfeld, AE Kunachiwa, W Leetrakool, N Hopkin, J Dunstan, S Hill, A Bodmer, W Beverley, PC Tchilian, EZ TI Geographical distribution and disease associations of the CD45 exon 6 138G variant SO IMMUNOGENETICS LA English DT Article DE CD45; A138G; alternative splicing; type I diabetes; hepatitis C ID POINT MUTATION; MULTIPLE-SCLEROSIS; CELL MATURATION; GENE; POLYMORPHISM; PTPRC; TUBERCULIN; INFECTION; RESPONSES; MICE AB CD45 is crucial for normal lymphocyte signalling, and altered CD45 expression has major effects on immune function. Both mice and humans lacking CD45 expression are severely immunodeficient, and single-nucleotide polymorphisms in the CD45 gene that cause altered splicing have been associated with autoimmune and infectious diseases. Recently, we identified an exon 6 A138G polymorphism resulting in an increased proportion of activated CD45RO T cells and altered immune function. Here we report a significantly reduced frequency of the 138G allele in hepatitis C Japanese patients and a possibly reduced frequency in type I diabetes. The allele is widely distributed in the Far East and India, indicating that it may have a significant effect on disease burden in a large part of the human population. C1 Edward Jenner Inst Vaccine Res, Compton RG20 7NN, Berks, England. John Radcliffe Hosp, Canc Res UK, Weatherall Inst Mol Med, Canc & Immunogenet Lab, Oxford OX3 9DU, England. Osaka City Univ, Grad Sch Med, Abeno Ku, Osaka 5458585, Japan. Kagoshima Univ, Grad Sch Med & Dent Sci, Kagoshima 8908520, Japan. Imperial Coll, Fac Med, Dept Immunol, London W2 1PG, England. UCL, Sch Med, Inst Urol & Nephrol, London W1N 8AA, England. Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Chiang Mai Univ, Dept Clin Immunol, Chiang Mai 50000, Thailand. Univ Coll Swansea, Swansea Clin Sch, Swansea, W Glam, Wales. Hosp Trop Dis, Ho Chi Minh City, Vietnam. RP Tchilian, EZ (reprint author), Edward Jenner Inst Vaccine Res, Compton RG20 7NN, Berks, England. EM elma.tchilian@jenner.ac.uk RI HILL, Adrian/C-1306-2008; Hennig, Branwen/M-6444-2014; OI Dunstan, Sarah/0000-0001-7873-933X; Bangham, Charles/0000-0003-2624-3599; Bodmer, Walter/0000-0001-6244-9792 NR 29 TC 9 Z9 9 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 EI 1432-1211 J9 IMMUNOGENETICS JI Immunogenetics PD APR PY 2006 VL 58 IS 2-3 BP 235 EP 239 DI 10.1007/s00251-006-0099-0 PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 028PQ UT WOS:000236500700016 PM 16538473 ER PT J AU Yamagata, T Benoist, C Mathis, D AF Yamagata, T Benoist, C Mathis, D TI A shared gene-expression signature in innate-like lymphocytes SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ACUTE MYELOID-LEUKEMIA; T-CELL-ACTIVATION; IFN-GAMMA; INTRAEPITHELIAL LYMPHOCYTES; NKT CELLS; INTRACELLULAR PATHOGENS; ADAPTIVE IMMUNITY; B-1 CELLS; B-CELLS; RECEPTORS AB Innate and adaptive immunities are the two major arms of the immune system, which rely on distinct cell types. These cells can be distinguished not only by the source of diversity for non-self recognition, of germline or somatic origin, but also by their localization and the pattern and rates of response after encounter of antigenic triggers. In addition, subsets of lymphocytes exist whose receptors require rearrangement but result in semi-invariant structures with a high degree of self-specificity. We hypothesized that these innate-like lymphocytes might share a common gene transcription signature that relates them to classic members of the innate immune system. This relationship was first observed in agonist-induced CD8 alpha alpha T cells in fetal/neonatal thymus. We then asked whether this notion could be extended to other innate-like lymphocytes, by comparison of gene expression profiles of innate-like lymphocytes and closely paired adaptive system counterparts (NKT versus CD4T, CD8 alpha alpha T versus CD8 alpha beta T, and B1 versus B2). A statistically significant 'innate signature' indeed was distilled. Particularly intriguing was the high representation of interferon-inducible guanosine triphophatases crucial for resistance against intracellular pathogens and of small G proteins involved in intracellular vacuole maturation and trafficking. Overall, this combined expression pattern can be designated as an innate signature among lymphocytes. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, Boston, MA 02215 USA. Dokkyo Med Sch, Dept Hematol, Tochigi, Japan. RP Mathis, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu NR 69 TC 43 Z9 43 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 52 EP 66 DI 10.1111/j.0105-2896.2006.00371.x PG 15 WC Immunology SC Immunology GA 026GO UT WOS:000236327600005 PM 16623764 ER PT J AU Borde, M Barrington, RA Heissmeyer, V Carroll, MC Rao, A AF Borde, M Barrington, RA Heissmeyer, V Carroll, MC Rao, A TI Transcriptional basis of lymphocyte tolerance SO IMMUNOLOGICAL REVIEWS LA English DT Review ID REGULATORY T-CELLS; E3 UBIQUITIN LIGASE; IMMATURE B-CELLS; KINASE-C-THETA; ANTIGEN-RECEPTOR; IN-VIVO; CUTTING EDGE; TGF-BETA; CBL-B; GENE-EXPRESSION AB Signaling through lymphocyte antigen receptors has the potential to initiate several distinct outcomes: proliferation, differentiation, apoptosis, or functional unresponsiveness. Expansion and differentiation of effector T cells is required for defense against foreign antigens, whereas functional unresponsiveness, termed anergy, is a cell-intrinsic mechanism that contributes to peripheral self-tolerance. Other mechanisms of peripheral tolerance include the 'dominant' tolerance imposed by regulatory T cells and immunosuppression mediated by interleukin-10 and transforming growth factor-beta. T- and B-cell antigen receptor ligation induces an increase in intracellular calcium levels as well as activating additional signaling pathways that are further potentiated by costimulatory receptors. In this review, we argue that cell-intrinsic programs of peripheral anergy and tolerance are imposed by sustained calcium signaling in lymphocytes. We address in particular the role of the calcium-dependent transcription factor nuclear factor for activation of T cells, which is activated by antigen receptor stimulation and, depending on the presence or absence of input from its transcriptional partner, activator protein-1, dictates two distinct transcriptional programs: activation or tolerance. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu NR 152 TC 37 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 105 EP 119 DI 10.1111/j.0105-2896.2006.00370.x PG 15 WC Immunology SC Immunology GA 026GO UT WOS:000236327600008 PM 16623767 ER PT J AU Benoist, C Germain, RN Mathis, D AF Benoist, C Germain, RN Mathis, D TI A Plaidoyer for 'systems immunology' SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material AB A complete understanding of the immune system will ultimately require an integrated perspective on how genetic and epigenetic entities work together to produce the range of physiologic and pathologic behaviors characteristic of immune function. The immune network encompasses all of the connections and regulatory associations between individual cells and the sum of interactions between gene products within a cell. With 30 000+ protein-coding genes in a mammalian genome, further compounded by microRNAs and yet unrecognized layers of genetic controls, connecting the dots of this network is a monumental task. Over the past few years, high-throughput techniques have allowed a genome-scale view on cell states and cell- or system-level responses to perturbations. Here, we observe that after an early burst of enthusiasm, there has developed a distinct resistance to placing a high value on global genomic or proteomic analyses. Such reluctance has affected both the practice and the publication of immunological science, resulting in a substantial impediment to the advances in our understanding that such large-scale studies could potentially provide. We propose that distinct standards are needed for validation, evaluation, and visualization of global analyses, such that in-depth descriptions of cellular responses may complement the gene/factor-centric approaches currently in favor. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, Boston, MA 02215 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Benoist, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU Intramural NIH HHS NR 0 TC 35 Z9 38 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 229 EP 234 DI 10.1111/j.0105-2896.2006.00374.x PG 6 WC Immunology SC Immunology GA 026GO UT WOS:000236327600015 PM 16623774 ER PT J AU Valera, EM Seidman, LJ AF Valera, EM Seidman, LJ TI Neurobiology of attention-deficit/hyperactivity disorder in preschoolers SO INFANTS AND YOUNG CHILDREN LA English DT Review DE ADHD; attention-deficit/hyperactivity disorder; neurobiology; neuroimaging; neuropsychology; preschoolers ID DEFICIT-HYPERACTIVITY DISORDER; FUNCTIONAL MAGNETIC-RESONANCE; LOW-BIRTH-WEIGHT; AGE-DEPENDENT DECLINE; TIME PERCEPTION; MORPHOMETRIC ANALYSIS; CLINICAL-ASSESSMENT; CORPUS-CALLOSUM; WORKING-MEMORY; BASAL GANGLIA AB There is abundant evidence that attention-deficit/hyperactivity disorder (ADHD) is a neurobiologic disorder. Yet, some of the most common methods for directly assessing neurobiologic substrates have not been used in 3- to 5-year-old preschoolers. Therefore, we must use other means to infer the neurobiology of ADHD in this young age group. In this review, we provide the following: (1) a brief review of neuropsychologic Studies of preschoolers with ADHD; (2) a brief summary of structural and functional neuroimaging studies of ADHD in older children as they might relate to findings in preschoolers; (3) an empirically based theory of the neurologic substrate of ADHD, in particular, the cerebellar-prefrontal-striatal network; (4) an overview of the evidence for the etiology of ADHD; and (5) support for the idea that the neurobiology of ADHD is largely stable over time, such that we can infer abnormalities in preschoolers on the basis of data from older children with ADHD. We hope that this information can be used to guide our thinking and treatment approaches in these young children with ADHD. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. RP Valera, EM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Room 2651,149 13th St, Charlestown, MA 02129 USA. EM eve_valera@hms.harvard.edu NR 106 TC 3 Z9 3 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0896-3746 J9 INFANT YOUNG CHILD JI Infants Young Child. PD APR-JUN PY 2006 VL 19 IS 2 BP 94 EP 108 PG 15 WC Education, Special; Psychology, Developmental; Rehabilitation SC Education & Educational Research; Psychology; Rehabilitation GA 028XC UT WOS:000236521100003 ER PT J AU Maeno, Y Nakazawa, S Yamamoto, N Shinzato, M Nagashima, S Tanaka, K Sasaki, J Rittling, SR Denhardt, DT Uede, T Taniguchi, K AF Maeno, Y Nakazawa, S Yamamoto, N Shinzato, M Nagashima, S Tanaka, K Sasaki, J Rittling, SR Denhardt, DT Uede, T Taniguchi, K TI Osteopontin participates in Th1-mediated host resistance against nonlethal malaria parasite Plasmodium chabaudi chabaudi infection in mice SO INFECTION AND IMMUNITY LA English DT Article ID BLOOD-STAGE MALARIA; DEFICIENT MICE; PROTECTIVE IMMUNITY; LACKING OSTEOPONTIN; GAMMA-INTERFERON; IL-12 PRODUCTION; IN-VIVO; EXPRESSION; CELLS; INDUCTION AB Osteopontin (OPN) knockout mice (OPN-KO mice) died of Plasinodium chabaudi chabaudi infection, although wild-type (WT) mice had self-limiting infections. OPN was detected in the WT mice at 2 days postinfection. OPN-KO mice produced significantly smaller amounts of interleukin-12 and gamma interferon than WT mice produced. These results suggested that OPN is involved in Th1-mediated immunity against malaria infection. C1 Fujita Hlth Univ, Sch Med, Dept Virol & Parasitol, Toyoake, Aichi 4701192, Japan. Nagasaki Univ, Inst Trop Med, Dept Protozool, Nagasaki 8528523, Japan. Fujita Hlth Univ Coll, Dept Pathol, Toyoake, Aichi 4701192, Japan. Forsyth Inst, Boston, MA 02115 USA. Rutgers State Univ, Dept Cell Biol & Neurosci, Div Life Sci, Piscataway, NJ 08854 USA. Hokkaido Univ, Inst Med Genet, Div Mol Immunol, Sapporo, Hokkaido 0600815, Japan. RP Maeno, Y (reprint author), Fujita Hlth Univ, Sch Med, Dept Virol & Parasitol, 1-98 Kutsukate, Toyoake, Aichi 4701192, Japan. EM ymaeno@fujita-hu.ac.jp RI uede, toshimitsu/A-4273-2012 NR 24 TC 13 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2006 VL 74 IS 4 BP 2423 EP 2427 DI 10.1128/IAI.74.4.2423-2427.2006 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028HF UT WOS:000236477000045 PM 16552072 ER PT J AU Rodriguez, M Hurtado, R AF Rodriguez, M Hurtado, R TI Primary hepatic non-Hodgkin lymphoma in an HIV-infected patient SO INFECTIONS IN MEDICINE LA English DT Editorial Material C1 Univ Alabama, Montgomery Internal Med Residency Program, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rodriguez, M (reprint author), Univ Alabama, Montgomery Internal Med Residency Program, Birmingham, AL 35294 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD APR PY 2006 VL 23 IS 4 BP 174 EP 174 PG 1 WC Infectious Diseases SC Infectious Diseases GA 034HW UT WOS:000236920900009 ER PT J AU Reinecker, HC AF Reinecker, HC TI Dentritic cell subspecifications in mucosal innate and adaptive immune defenses SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT 4th International Meeting on Inflammatory Bower Diseases CY APR 09-12, 2006 CL Capri, ITALY SP European Crohns & Colitis Org, European Federat Crohns & Ulcerat Colitis Assoc, Crohns & Colitis Fdn Amer, Italian Assoc Chron Inflammatory Bowel Dis C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, GI Unit Ctr Study Inflammatory Bowel Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2006 VL 12 SU 2 BP S4 EP S4 DI 10.1097/00054725-200604002-00012 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030KN UT WOS:000236633500010 ER PT J AU Sands, BE AF Sands, BE TI GM-CSF: does it work and how does it work? SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT 4th International Meeting on Inflammatory Bower Diseases CY APR 09-12, 2006 CL Capri, ITALY SP European Crohns & Colitis Org, European Federat Crohns & Ulcerat Colitis Assoc, Crohns & Colitis Fdn Amer, Italian Assoc Chron Inflammatory Bowel Dis ID ACTIVE CROHNS-DISEASE; COLONY-STIMULATING FACTOR C1 Massachusetts Gen Hosp, Gastrointestinal Unit, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2006 VL 12 SU 2 BP S12 EP S12 DI 10.1097/00054725-200604002-00024 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030KN UT WOS:000236633500022 ER PT J AU Daoud, YJ Amin, KG AF Daoud, YJ Amin, KG TI Comparison of cost of immune globulin intravenous therapy to conventional immuno suppressive therapy in treating patients with autoimmune mucocutaneous blistering diseases SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE conventional immunosuppressive therapy; intravenous immunoglobulin therapy; autoimmune mucocutaneous blistering diseases; pharmacoeconomics; cost of side-effects; total cost of care ID BONE-MARROW TRANSPLANTATION; IMMUNOGLOBULIN THERAPY; PEMPHIGUS-VULGARIS; IMMUNOSUPPRESSIVE TREATMENT/; SYSTEMIC CHEMOTHERAPY; REMISSION AB Autoimmune mucocutaneous blistering diseases (AMBD) are a group of potentially fatal diseases that affect the skin and mucous membranes. AMBD have different target antigens as well as variable clinical presentation, course, and prognosis. The mainstay of conventional immunosuppressive therapy (CIST) for AMBD is long-term high-dose systemic corticosteroids and immunosuppressive agents. Such therapy has proven effective in many patients; however, in some patients, the disease continues to progress with significant sequelae such as blindness, loss of voice, anal, and vaginal stenosis which causes poor quality of life. Furthermore, the CIST may have some serious side effects including opportunistic infections which may cause death. Immune globulin intravenous (IGIV) therapy has been reportedly used in the management of patients with AMBD refractory to CIST. IGIV has shown to be more clinically beneficial than CIST by bringing about long-term clinical remission and less recurrence. The high cost of the IGIV is of concern to patients, physicians, and insurance companies. In this report, we compare the cost of IGIV to that of CIST in treating a cohort of 15 mucous membrane pemphigoid (MMP), 10 ocular cicatricial pemphigoid (OCP), 15 bullous pemphigoid (BP), and 32 pemphigus vulgaris (PV) patients. In each cohort of patients, CIST had significant side effects, many of which were hazardous and required prolonged and frequent hospitalizations. Some of these side effects were severe enough to require discontinuation of the treatment. We consider the total cost of CIST to be the actual cost of the drug, plus the cost of management of the side effects produced by CIST. In the same patient cohort, no significant side effects to IGIV were observed. None of the IGIV treated patients required physician visits, laboratory tests, or hospitalizations specifically related to IGIV therapy. Hence, the total cost of the IGIV therapy is the actual cost of the IGIV only. The mean total cost of treatment of IGIV therapy is statistically significantly less than that of CIST during the entire course of the disease and on an annual basis. In conclusion, IGIV therapy is a safe, clinically beneficial, and a cost effective alternative treatment in patients with AMBD, non-responsive to CIST. (c) 2005 Elsevier B.V All rights reserved. C1 New England Baptist Hosp, Ctr Blistering Dis, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Cambridge, MA 02138 USA. RP Daoud, YJ (reprint author), New England Baptist Hosp, Ctr Blistering Dis, Dept Med, 70 Parker Hill,Ave 208, Boston, MA 02120 USA. EM centerforblisteringdiseases@msn.com NR 34 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2006 VL 6 IS 4 BP 600 EP 606 DI 10.1016/j.intimp.2005.11.002 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 023WF UT WOS:000236156200011 PM 16504922 ER PT J AU Weingart, SN Pagovich, O Sands, DZ Li, JM Aronson, MD Davis, RB Phillips, RS Bates, DW AF Weingart, SN Pagovich, O Sands, DZ Li, JM Aronson, MD Davis, RB Phillips, RS Bates, DW TI Patient-reported service quality on a medicine unit SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Review DE service quality; healthcare quality; patient-centered care; patient satisfaction ID ADVERSE DRUG EVENTS; HEALTH-CARE; HOSPITAL-CARE; SATISFACTION; EXPECTATIONS; MEDICARE; OUTCOMES AB Purpose. Service quality, defined as patients' self-reported experience of care, is used as a metric for evaluating quality. Most studies rely on retrospective consumer surveys rather then more intensive data collection methods, possibly underestimating the incidence of service quality incidents. Subjects and Methods. The objective of the study was to characterize patient-reported service quality deficiencies on a general medicine unit. We studied a cohort of 228 adult inpatients at a Boston teaching hospital. Investigators reviewed medical records and interviewed patients during the hospitalization and by telephone after discharge. Physician investigators classified patients' incident reports. We calculated the rate of service incidents, characterized incident types, and used multivariable Poisson and logistic regression models to examine factors associated with patient reporting and overall rating of the hospitalization. Results. Eighty-eight (38.6%) of 228 patients experienced 157 service quality incidents during the admission, for a rate of 68.9 incidents per 100 admissions. The most common service quality problems involved waits and delays (n = 45), problems with communication between staff and patients (n = 36), and environmental issues and amenities (n = 35). In the multivariable analysis, men (IRR 1.6, 95% CI 1.1-2.2), patients covered by hospitalists (1.5, 1.1-2.2), and patients with more medication allergies (1.1 per allergy, 1.1-1.2) reported more service incidents; patients with Medicaid or free care reported fewer (0.5, 0.3-0.9). Patients with service quality incidents were more likely to describe the hospitalization as other than excellent (adjusted OR 1.8 per incident, 95% CI 1.3-2.5). Conclusion. Service quality deficiencies are common among medical inpatients, and are strongly associated with patients' dissatisfaction with the hospitalization. C1 Beth Israel Deaconess Med Ctr, Ctr Patient Safety, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02115 USA. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Zix Corp, Dallas, TX USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weingart, SN (reprint author), Beth Israel Deaconess Med Ctr, Ctr Patient Safety, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu NR 24 TC 16 Z9 18 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD APR PY 2006 VL 18 IS 2 BP 95 EP 101 DI 10.1093/intqhc/mzi087 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 027RZ UT WOS:000236434400004 PM 16282334 ER PT J AU Ray, KK Sheridan, PJ Bolton, J Clayton, TC Veitch, A Manivarmane, R Al Rifai, A Payne, G Baig, W AF Ray, KK Sheridan, PJ Bolton, J Clayton, TC Veitch, A Manivarmane, R Al Rifai, A Payne, G Baig, W TI Management and outcomes of acute coronary syndrome with minimal myocardial necrosis: analysis of a large prospective registry from a non-interventional centre SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article DE ACS; troponin; myonecrosis; registry; prognosis ID CARDIAC TROPONIN-T; ST-SEGMENT ELEVATION; ACUTE CHEST-PAIN; EMERGENCY-DEPARTMENT PATIENTS; CLINICAL-OUTCOMES; CARDIOVASCULAR EVENTS; FIBRINOLYTIC THERAPY; RISK STRATIFICATION; I LEVELS; INFARCTION AB The aim of this study was to assess the clinical risk of minimal myonecrosis below the cut-off for acute myocardial infarction (MI) in comparison with other grades of acute coronary syndrome (ACS). One-thousand four hundred and sixty seven consecutive patients with ACS admitted between May 2001 and April 2002 were studied in a non-interventional centre. Patients were divided into unstable angina (UA) (cTnT < 0.01 mu g/l), non-ST elevation ACS with minimal myonecrosis (0.01 <= cTnT < 0.1 mu g/l), non-ST elevation MI (NSTEMI) (cTnT >= 0.1 mu g/L) and ST elevation myocardial infarction (STEMI). UA (n = 638) was associated with the fewest events at 6 months (2% cardiac death or MI). Patients with any myonecrosis (n = 829) had worse outcomes (6-month cardiac death or MI 18.3-23.3%). Compared with ACS patients with minimal myonecrosis, UA patients were at significantly lower risk (OR 0.21, 95% Cl 0.12-0.45, p < 0.001), NSTEMI patients were at similar risk (OR 1.45, 95% Cl 0.89-2-35, p = 0.13), and NSTEMI patients were at higher risk (OR 2.12 95% Cl 1.26-3.85, p = 0.008) in adjusted analyses. Nearly 85% of cardiac deaths occurred within 6 months. The risk of adverse events was higher among patients managed by non-cardiologists (OR 1.66, 95% Cl 1-2.75, p = 0.049). Patients with non-ST elevation ACS and minimal myonecrosis are a high-risk group more comparable with NSTEMI and clearly distinguishable from patients with UA. C1 London Sch Hyg & Trop Med, London WC1, England. Doncaster Royal Infirm, Dept Cardiol, Doncaster DN2 5LT, England. RP Ray, KK (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM kkray@partners.org NR 26 TC 0 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD APR PY 2006 VL 60 IS 4 BP 383 EP 390 DI 10.1111/j.1368-5031.2006.00816.x PG 8 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 036GA UT WOS:000237058400004 PM 16620349 ER PT J AU Schumacher, HR Becker, MA Edwards, NL Palmer, WE MacDonald, PA Palo, W Joseph-Ridge, N AF Schumacher, HR Becker, MA Edwards, NL Palmer, WE MacDonald, PA Palo, W Joseph-Ridge, N TI Magnetic resonance imaging in the quantitative assessment of gouty tophi SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article DE tophaceous gout; gadolinium; magnetic resonance imaging; quantitative assessment ID TOPHACEOUS GOUT; ULTRASONOGRAPHY; MANAGEMENT AB Measurements of tophus size can be important in monitoring the course of gout therapy, as tophus resolution Is proposed as one measure of success of treatment. This multicentre Study assessed the intra- and interreader reproducibility of quantitative tophus volume measurements from magnetic resonance images (MRI) in subjects with palpable gouty tophi. Subjects first under-went radiographic imaging of a selected tophus followed by MRI before and at <= 5, 10 and 20-min after gadolinium administration. After choosing optimal parameters, subjects underwent pre- and postgadolinium-enhanced MRIs of a selected tophus on two occasions separated by 5-10 days. Unenhanced spin-echo images provided satisfactory tophi images and were less subject to interfering artefacts than gadolinium-enhanced gradient-echo images. Intrareader reproducibility was excellent, with no statistically significant difference in mean tophus volume between visits (mean difference -0.05 +/- 0.97 cm(3)). A small but statistically significant difference in interreader mean tophus volume was detected (mean difference 0.89 +/- 2.05 cm(3); p < 0.05). MRI can quantify tophus size in gout and deserves further comparison with other techniques for tophus size monitoring in assessing effects of gout therapy. C1 Univ Penn, Philadelphia, PA 19104 USA. VA Med Ctr, Philadelphia, PA USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Univ Florida, Gainesville, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Schumacher, HR (reprint author), Univ Penn, 151K Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu NR 18 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD APR PY 2006 VL 60 IS 4 BP 408 EP 414 DI 10.1111/j.1368-5031.2006.00853.x PG 7 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 036GA UT WOS:000237058400007 PM 16620352 ER PT J AU Schobel, S Neumann, S Seed, B Lichtenthaler, SE AF Schobel, S Neumann, S Seed, B Lichtenthaler, SE TI Expression cloning screen for modifiers of amyloid precursor protein shedding SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT International Conference on Neural Signal Transduction in Health and Disease CY OCT, 2005 CL Leipzig, GERMANY SP German Soc Biochem & Mole Biol, Study Grp Neurochem, Interdisciplinary Ctr Clin Res, Univ Leipzig, Grad Coll InterNeuro, Deutsch Forsch Gemeinsch DE ectodomain shedding; amyloid precursor protein; Alzheimer's disease; endocytosis ID SELECTIN GLYCOPROTEIN LIGAND-1; ALPHA-SECRETASE ACTIVITY; BETA-APP; METALLOPROTEASE-DISINTEGRINS; ALZHEIMERS-DISEASE; DOWN-REGULATION; MEMBRANE; ACTIVATION; ECTODOMAIN; KINASE AB Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the amyloid beta peptide (A beta), which is thought to provoke the pathogenesis of Alzheimer's disease. To better understand the cellular processes that regulate ectodomain shedding of APP we used human embryonic kidney 293 cells and applied a sib-selection expression cloning approach. In addition to a known activator of APP shedding - protein kinase A - the following cDNAs were identified: the endocytic proteins endophilin A1 and A3, the metabotropic glutamate receptor 3 (mGluR3), palmitoyl-protein thioesterase 1 (PPT1), Numb-like and the kinase MEKK2. Endophilins A1 and A3, as well as mGluR3 activated APP shedding relatively specifically. They had little or no effect on the shedding of the unrelated membrane proteins TNF receptor 2 and P-selectin glycoprotein ligand-1. In contrast, MEKK2 and PKA also increased shedding of TNF receptor 2, suggesting that these kinases contribute to a general program regulating ectodomain shedding. The strongest activator of APP shedding, endophilin A3, reduced the rate of APP endocytosis and specifically increased APP shedding by the protease alpha-secretase, as measured in an antibody uptake assay and by immunoblot analysis. This suggests that endophilin A3 is a novel modulator of APP trafficking affecting access of APP to alpha-secretase. In summary, this study shows that expression cloning is a suitable way to identify proteins controlling ectodomain shedding of membrane proteins. (c) 2005 ISDN. Published by Elsevier Ltd. All rights reserved. C1 Univ Munich, Adolf Butenandt Inst, D-80336 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lichtenthaler, SE (reprint author), Univ Munich, Adolf Butenandt Inst, Schillerstr 44, D-80336 Munich, Germany. EM Stefan.Lichtenthaler@med.uni-muenchen.de RI Lichtenthaler, Stefan/B-6587-2016 OI Lichtenthaler, Stefan/0000-0003-2211-2575 NR 48 TC 21 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD APR-MAY PY 2006 VL 24 IS 2-3 BP 141 EP 148 DI 10.1016/j.ijdevneu.2005.11.003 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 024DO UT WOS:000236175400007 PM 16446073 ER PT J AU Irving, JA Vasques, DR McGuinness, TB Young, RH AF Irving, JA Vasques, DR McGuinness, TB Young, RH TI Krukenberg tumor of renal pelvic origin: Report of a case with selected comments on ovarian tumors metastatic from the urinary tract SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; renal pelvis; metastasis; Krukenberg turnor ID TRANSITIONAL-CELL-CARCINOMA; DIFFERENTIAL-DIAGNOSIS; ADENOCARCINOMA; BLADDER AB Metastatic tumors to the ovary are infrequently of urinary tract origin. In approximate descending order of frequency, this subset of secondary ovarian neoplasms includes renal cell carcinoma, transitional cell carcinoma of the urinary bladder, and urachal adenocarcinomas. These tumors usually raise it differential in turn of primary ovarian clear cell, transitional cell, or mucinous carcinomas. Only rare metastatic signet-ring adenocarcinomas of the bladder have shown the features of a Krukenberg tumor. We report the case of a 74-year old woman with bilateral Krukenberg tumors metastatic from a primary renal pelvic transitional cell carcinoma with glandular and signet-ring cell differentiation. This unique case reinforces that tumors with signet-ring cell morphology have a propensity to metastasize to the ovary, and indicates that renal pelvic, carcinoma rarely may be the source of Krukenberg tumors. C1 Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Wellspan Hlth Syst, Div Gynecol Oncol, York, PA USA. Wellspan Hlth Syst, York Womens Hlth Ctr, York, PA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Irving, JA (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12Th Ave, Vancouver, BC V5Z 1M9, Canada. EM jirving@vanhosp.bc.ca NR 24 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 2006 VL 25 IS 2 BP 147 EP 150 DI 10.1097/01.pgp.0000185405.08556.a0 PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 032LB UT WOS:000236774800005 PM 16633063 ER PT J AU Geller, M Ribeiro, MG Araujo, APDC de Oliveira, LJB Nunes, FP AF Geller, M Ribeiro, MG Araujo, APDC de Oliveira, LJB Nunes, FP TI Serum IgE levels in neurofibromatosis 1 SO INTERNATIONAL JOURNAL OF IMMUNOGENETICS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MAST-CELLS; PLEXIFORM NEUROFIBROMAS; IMMUNOGLOBULIN-E; CARCINOMA; CANCER; STRONGYLOIDIASIS; ANGIOGENESIS AB A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1). The patients were divided into groups, with 25 patients presenting plexiform neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas. The purposes of this study were to determine the serum IgE levels of patients with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas, as well as to determine possible correlations between serum IgE levels and the size of the plexiform neurofibromas and neurofibromas presented by these patients. Elevated serum IgE levels were observed in all the patient groups. We did not observe a correlation between IgE levels and age in these patients; however, we did observe correlations between IgE levels and neurofibroma and plexiform neurofibroma size. We suggest further studies to confirm these results and to investigate in greater depth the possible role of IgE in the development and growth of neurofibromas and plexiform neurofibromas in NF1. C1 Teresopolis Med Sch, FESO, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. Unigranrio Univ, Rio De Janeiro, Brazil. Harvard Univ, Massachusetts Gen Hosp, Charlestown, MA USA. RP Geller, M (reprint author), Av Ataulfo Paiva,135 S 1104, BR-22440030 Rio De Janeiro, Brazil. EM mgeller@infolink.com.br OI Ribeiro, Marcia/0000-0001-8906-0189 NR 35 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3121 J9 INT J IMMUNOGENET JI Int. J. Immunogenet. PD APR PY 2006 VL 33 IS 2 BP 111 EP 115 DI 10.1111/j.1744-313X.2006.00579.x PG 5 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 022ON UT WOS:000236065500008 PM 16611255 ER EF