FN Thomson Reuters Web of Science™ VR 1.0 PT S AU Tramo, MJ Cariani, PA Koh, CK Makris, N Braida, LD AF Tramo, MJ Cariani, PA Koh, CK Makris, N Braida, LD BE Avanzini, G Koelsch, S Lopez, L Majno, M TI Neurophysiology and neuroanatomy of pitch perception: Auditory cortex SO NEUROSCIENCES AND MUSIC II: FROM PERCEPTION TO PERFORMANCE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference of the Neurosciences and Music II CY MAY 05-08, 2005 CL Lipzig, GERMANY SP Max Planck Inst Human Cognit & Brain Sci DE pitch; missing fundamental; psychophysics; periodicity; autocorrelation; auditory cortex; lesion effects; neural coding ID FREQUENCY DISCRIMINATION; INFERIOR COLLICULUS; COMPLEX TONES; TEMPORAL CHARACTERISTICS; SENSITIVE NEURONS; PERIODICITY PITCH; ACOUSTIC STIMULI; NERVOUS-SYSTEM; REPRESENTATION; RESPONSES AB We present original results and review literature from the past fifty years that address the role of primate auditory cortex in the following perceptual capacities: (1) the ability to perceive small differences between the pitches of two successive tones; (2) the ability to perceive the sign (i.e., direction) of the pitch difference [higher (+) vs. lower (-)]; and (3) the ability to abstract pitch constancy across changes in stimulus acoustics. Cortical mechanisms mediating pitch perception are discussed with respect to (1) gross and microanatomical distribution; and (2) candidate neural coding schemes. Observations by us and others suggest that (1) frequency-selective neurons in primary auditory cortex (A1) and surrounding fields play a critical role in fine-grained pitch discrimination at the perceptual level; (2) cortical mechanisms that detect pitch differences are neuroanatomically dissociable from those mediating pitch direction discrimination; (3) cortical mechanisms mediating perception of the "missing fundamental frequency (F0)" are neuroanatomically dissociable from those mediating pitch perception when F0 is present; (4) frequency-selective neurons in both right and left A1 contribute to pitch change detection and pitch direction discrimination; (5) frequency-selective neurons in right Al are necessary for normal pitch direction discrimination; (6) simple codes for pitch that are based on single- and multiunit firing rates of frequency-selective neurons face both a "hyperacuity problem" and a "pitch constancy problem"-that is, frequency discrimination thresholds for pitch change direction and pitch direction discrimination are much smaller than neural tuning curves predict, and firing rate patterns change dramatically under conditions in which pitch percepts remain invariant; (7) cochleotopic organization of frequency-selective neurons bears little if any relevance to perceptual acuity and pitch constancy; and (8) simple temporal codes for pitch capable of accounting for pitches higher than a few hundred hertz have not been found in the auditory cortex. The cortical code for pitch is therefore not likely to be a function of simple rate profiles or synchronous temporal patterns. Studies motivated by interest in the neurophysiology and neuroanatomy of music perception have helped correct longstanding misconceptions about the functional role of auditory cortex in frequency discrimination and pitch perception. Advancing knowledge about the neural coding of pitch is of fundamental importance to the future design of neurobionic therapies for hearing loss. C1 Inst Mus & Brain Sci, Auditory Neurosci Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Sensory Commun Grp, Res Lab Elect, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. RP Tramo, MJ (reprint author), Inst Mus & Brain Sci, Auditory Neurosci Program, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM mtramo@hms.harvard.edu FU NIDCD NIH HHS [DC00117, DC006353, DC03328] NR 107 TC 26 Z9 28 U1 0 U2 17 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-610-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1060 BP 148 EP 174 DI 10.1196/annals.1360.011 PG 27 WC Multidisciplinary Sciences; Music; Clinical Neurology; Psychology; Psychology, Experimental SC Science & Technology - Other Topics; Music; Neurosciences & Neurology; Psychology GA BEE76 UT WOS:000236996500018 PM 16597761 ER PT J AU Nimsky, C Ganslandt, O Hastreiter, P Wang, RP Benner, T Sorensen, AG Fahlbusch, R AF Nimsky, C Ganslandt, O Hastreiter, P Wang, RP Benner, T Sorensen, AG Fahlbusch, R TI Preoperative and intraoperative diffusion tensor imaging-based fiber tracking in glioma surgery SO NEUROSURGERY LA English DT Article DE diffusion tensor imaging; fiber tracking; functional imaging; glioma surgery; intraoperative high-field magnetic resonance imaging; tractography; white matter tracts ID FUNCTIONAL MAGNETIC-RESONANCE; WHITE-MATTER ANATOMY; BRAIN-TUMORS; IN-VIVO; PYRAMIDAL TRACT; MOTOR CORTEX; MRI; NEURONAVIGATION; SHIFT; MAGNETOENCEPHALOGRAPHY AB OBJECTIVE: To investigate the intraoperative displacement of major white matter tracts during glioma resection by comparing preoperative and intraoperative diffusion tensor imaging-based fiber tracking. METHODS: In 37 patients undergoing glioma surgery, preoperative and intraoperative diffusion tensor imaging was performed with a 1.5-T magnetic resonance scanner applying an echo-planar imaging sequence with six diffusion directions. For three-dimensional tractography, we implemented a knowledge-based multiple-region-of-interest approach applying user-defined seed regions in the color-coded maps of fractional anisotropy. Tracking was initiated in both the retrograde and orthograde directions according to the direction of the principal eigenvector in each voxel of the region of interest. The tractography results were also assigned color, applying the convention used in color-coded fractional anisotropy maps. RESULTS: Preoperative and intraoperative fiber tracking was technically feasible in all patients. Fiber tract visualization gave a quick and intuitive overview of the displaced course of white matter tracts in three-dimensional space. Comparison of preoperative and intraoperative tractography depicted a marked shifting of major white matter tracts during glioma removal. Maximum white matter tract shifting ranged from -8 to +15 mm (+2.7 -6.0 mm; mean +/- standard deviation); in 29.7%, an inward and in 62.2%, an outward shifting was detected. CONCLUSION: Comparing preoperative and intraoperative fiber tracking visualizes a marked shifting and deformation of major white matter tracts because of tumor removal. This shifting emphasizes the need for an intraoperative update of navigation systems during resection of deep-seated tumor portions near eloquent brain areas. Fiber tracking is a method not only for preoperative neurosurgical visualization but also for further intraoperative planning. C1 Univ Erlangen Nurnberg, Dept Neurosurg, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Boston, MA 02114 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 FU NCRR NIH HHS [P41-RR14075, M01-RR001066]; NINDS NIH HHS [NS-038477] NR 49 TC 210 Z9 231 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2005 VL 56 IS 1 BP 130 EP 137 DI 10.1227/01.NEU.0000144842.18771.30 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 884FD UT WOS:000226069300041 PM 15617595 ER PT J AU Neimat, JS Hoh, BL McKenna, MJ Rabinov, JD Ogilvy, CS AF Neimat, JS Hoh, BL McKenna, MJ Rabinov, JD Ogilvy, CS TI Aneurysmal expansion presenting as facial weakness: Case report and review of the literature SO NEUROSURGERY LA English DT Article DE aneurysm; anteroinferior cerebellar artery; cerebellopontine angle syndrome; facial palsy C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Serv, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. RP Neimat, JS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Serv, Cambridge, MA 02138 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 2005 VL 56 IS 1 BP 190 EP 190 DI 10.1227/01.NEU.000014611.62306.CD PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 884FD UT WOS:000226069300058 PM 15617605 ER PT J AU Cruz, LCH Sorensen, AG AF Cruz, LCH Sorensen, AG TI Diffusion tensor magnetic resonance imaging of brain tumors SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID INTRAVOXEL INCOHERENT MOTION; GRADE CEREBRAL GLIOMAS; WHITE-MATTER; IN-VIVO; INTRACRANIAL TUMORS; PYRAMIDAL TRACTS; WATER DIFFUSION; FUNCTIONAL MRI; MOTOR CORTEX; WEIGHTED MRI AB Diffusion tensor imaging (DTI) appears to offer the possibility of adding important information to aid in presurgical planning. Although experience is limited, DTI seems to provide useful local information about the structures near the tumor. In the future, DTI may provide an improved way to monitor intraoperative surgical procedures as well as their effects. Evaluation of the response to treatment with chemotherapy and radiation therapy may also become possible. Although DTI has some limitations, its active investigation and further study are clearly warranted. C1 Harvard Mit, Dept Radiol,Div Hlth Sci & Technol, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02421 USA. MultiImagem Ressonancia Magnet, Clin Diagnost Imagem, Rio De Janeiro, Brazil. RP Sorensen, AG (reprint author), Harvard Mit, Dept Radiol,Div Hlth Sci & Technol, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149M 13th St, Boston, MA 02421 USA. EM sorensen@nmr.mgh.harvard.edu NR 89 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 2005 VL 16 IS 1 BP 115 EP + DI 10.1016/j.nec.2004.07.007 PG 21 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 881KY UT WOS:000225867600006 PM 15561532 ER PT J AU Martin-Rehrmann, MD Hoe, HS Capuani, EM Rebeck, GW AF Martin-Rehrmann, MD Hoe, HS Capuani, EM Rebeck, GW TI Association of apolipoprotein J-positive beta-amyloid plaques with dystrophic neurites in Alzheimer's disease brain SO NEUROTOXICITY RESEARCH LA English DT Article DE clusterin; immunofluorescence; SP-40,40; tau ID A-BETA; MOUSE MODEL; SENILE PLAQUES; DOWNS-SYNDROME; DEPOSITION; CLUSTERIN; PROTEIN; ACCUMULATION; AGGREGATION; EXPRESSION AB Apolipoprotein J (apoJ), also known as clusterin and SP-40,40, binds soluble beta-amyloid (Aβ and is up-regulated in the Alzheimer's disease (AD) brain. In the present study we classified apoJ-immunopositive Aβ deposits in AD temporal cortex, and found apoJ-immunoreactive plaques were often associated with dystrophic neurites. Quantitative immunohistochemical analysis of five AD brains showed that 29% of Aβ deposited in the parenchyma was associated with apoJ. Of Aβ deposits with apoj immunopositivity, 71% were associated with phospho-tau-positive dystrophic neurites in the surrounding tissue. Conversely, 64% of phospho-tau-labeled neuritic deposits were labeled with apoj. ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S. To test the direct effects of apoj on tau metabolism, we treated cells in culture with apoJ-containing conditioned media, and we injected apoJ-containing media into the rat hippocampus. Using both systems, we observed increases in levels of tau and phosphorylated tau. Our findings demonstrate that apoJ immunopositivity strongly correlates with the presence of amyloid and associated neuritic dystrophy in the neuropil of AD temporal cortex, and supports a model where extracellular apoj facilitates the conversion of diffuse Aβ deposits into amyloid and enhances tau phosphorylation in neurites surrounding these plaques. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. Georgetown Univ, Ctr Med, Dept Neurosci, Washington, DC 20007 USA. Univ Tubingen, Int Max Planck Res Sch, Grad Sch Neural & Behav Sci, Tubingen, Germany. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM gwr2@georgetown.edu FU NCHM CDC HHS [HM31862]; NIA NIH HHS [AG05134, AG14473] NR 39 TC 18 Z9 18 U1 0 U2 1 PU F P GRAHAM PUBLISHING CO PI MOUNTAIN HOME PA PO BOX 370, MOUNTAIN HOME, TN 37684 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PY 2005 VL 7 IS 3 BP 231 EP 241 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 931WT UT WOS:000229516900006 PM 15897157 ER PT J AU Cristofaro, V Hofer, A Yalla, S Curci, S Sullivan, M AF Cristofaro, V Hofer, A Yalla, S Curci, S Sullivan, M TI Activation of calcium-sensing receptor modulates bladder smooth muscle contraction SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Continence-Society CY AUG 28-SEP 02, 2005 CL Montreal, CANADA SP Int Continence Soc C1 VA Boston Healthcare Syst, Boston, MA USA. NR 3 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 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2005 VL 24 IS 5-6 MA 22 BP 439 EP 441 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 953CD UT WOS:000231052600023 ER PT J AU Burgio, K Goode, P Urban, D Umlauf, M Locher, J Bueschen, A Redden, D AF Burgio, K Goode, P Urban, D Umlauf, M Locher, J Bueschen, A Redden, D TI Preoperative biofeedback-assisted behavioral training to reduce post-prostatectomy incontinence: A randomized controlled trial SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Continence-Society CY AUG 28-SEP 02, 2005 CL Montreal, CANADA SP Int Continence Soc C1 Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2005 VL 24 IS 5-6 MA 46 BP 477 EP 478 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 953CD UT WOS:000231052600047 ER PT J AU Azadzoi, K Yalla, S Siroky, M AF Azadzoi, K Yalla, S Siroky, M TI Role of ischemia and oxidative stress in bladder neurodegeneration SO NEUROUROLOGY AND URODYNAMICS LA English DT Meeting Abstract CT 35th Annual Meeting of the International-Continence-Society CY AUG 28-SEP 02, 2005 CL Montreal, CANADA SP Int Continence Soc C1 Boston Univ, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. NR 0 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 0733-2467 J9 NEUROUROL URODYNAM JI Neurourol. Urodyn. PY 2005 VL 24 IS 5-6 MA 105 BP 566 EP 567 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 953CD UT WOS:000231052600106 ER PT J AU Keung, E Xue, Y AF Keung, Edmund Xue, Yang BE Wang, PJ TI Remote web-based device monitoring SO NEW ARRHYTHMIA TECHNOLOGIES LA English DT Article; Book Chapter ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; PACEMAKER C1 [Keung, Edmund] VA Natl ICD Surveillance Ctr, San Francisco, CA 94121 USA. [Keung, Edmund] Western Pacemaker Surveillance Ctr, San Francisco, CA USA. [Keung, Edmund] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. [Xue, Yang] Univ Michigan, Sch Med, Fremont, CA USA. RP Keung, E (reprint author), VA Natl ICD Surveillance Ctr, San Francisco, CA 94121 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98872-5 PY 2005 BP 206 EP 218 DI 10.1002/9780470988725.ch22 D2 10.1002/9780470988725 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BYE83 UT WOS:000298280100022 ER PT B AU Cascio, EW Sisterson, JM Slopsema, R AF Cascio, EW Sisterson, JM Slopsema, R GP IEEE TI Secondary neutron fluence in radiation test beams at The Northeast Proton Therapy Center SO NSREC: 2005 IEEE Radiation Effects Data Workshop, Workshop Record LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop CY JUL 11-15, 2005 CL Seattle, WA SP IEEE AB The fluence of secondary neutrons in the radiation effects test beams at The Northeast Proton Therapy Center is characterized. C1 Massachusetts Gen Hosp, NE Proton TherapyCtr, Boston, MA 02114 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, NE Proton TherapyCtr, Boston, MA 02114 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-9367-8 PY 2005 BP 175 EP 178 PG 4 WC Engineering, Aerospace; Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA BDP04 UT WOS:000234645600029 ER PT J AU Meng, Z King, PH Nabors, LB Jackson, NL Chen, CY Emanuel, PD Blume, SW AF Meng, Z King, PH Nabors, LB Jackson, NL Chen, CY Emanuel, PD Blume, SW TI The ELAV RNA-stability factor HuR binds the 5 '-untranslated region of the human IGF-IR transcript and differentially represses cap-dependent and IRES-mediated translation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GROWTH-FACTOR-I; 5' UNTRANSLATED REGION; AU-RICH ELEMENT; CYTOPLASMIC SHUTTLING PROTEIN; CONTAINING MESSENGER-RNAS; RIBOSOME ENTRY SITES; TUMOR-SUPPRESSOR WT1; RECEPTOR GENE; PHOSPHATIDYLINOSITOL 3-KINASE; INITIATION-FACTOR AB The type I insulin-like growth factor receptor (IGF-IR) is an integral component in the control of cell proliferation, differentiation and apoptosis. The IGF-IR mRNA contains an extraordinarily long (1038 nt) 5'-untranslated region (5'-UTR), and we have characterized a diverse series of proteins interacting with this RNA sequence which may provide for intricate regulation of IGF-IR gene expression at the translational level. Here, we report the purification and identification of one of these IGF-IR 50-UTR- binding proteins as HuR, using a novel RNA crosslinking/ RNase elution strategy. Because HuR has been predominantly characterized as a 3'-UTR- binding protein, enhancing mRNAstability and generally increasing gene expression, we sought to determine whether HuR might serve a different function in the context of its binding the IGF-IR 5'-UTR. We found that HuR consistently repressed translation initiation through the IGF-IR 5'-UTR. The inhibition of translation by HuR was concentration dependent, and could be reversed in trans by addition of a fragment of the IGF-IR5'-UTR containing the HuR binding sites as a specific competitor, or abrogated by deletion of the third RNA recognition motif of HuR. We determined that HuR repressed translation initiation through the IGF-IR 5'-UTR in cells as well, and that siRNA knockdown of HuR markedly increased IGF-IR protein levels. Interestingly, we also found that HuR potently inhibited IGF-IR translation mediated through internal ribosome entry. Kinetic assays were performed to investigate the mechanism of translation repression by HuR and the dynamic interplay between HuR and the translation apparatus. We found that HuR, occupying a cap-distal position, significantly delayed translation initiation mediated by cap-dependent scanning, but was eventually displaced from its binding site, directly or indirectly, as a consequence of ribosomal scanning. However, HuR perpetually blocked the activity of the IGF-IR IRES, apparently arresting the IRES-associated translation preinitiation complex in an inactive state. This function of HuR as a 5'-UTR-binding protein and dual-purpose translation repressor may be critical for the precise regulation of IGF-IR expression essential to normal cellular homeostasis. C1 Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Blume, SW (reprint author), Univ Alabama, Wallace Tumor Inst, 1824 6th Ave S,Room 508, Birmingham, AL 35294 USA. EM scott.blume@ccc.uab.edu OI Emanuel, Peter/0000-0002-9764-2434 FU NCI NIH HHS [CA80916, CA108886, K24 CA080916, R01 CA108886] NR 76 TC 71 Z9 72 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 9 BP 2962 EP 2979 DI 10.1093/nar/gki603 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932HK UT WOS:000229544600028 PM 15914670 ER PT J AU Esensten, JH Tsytsykova, AV Lopez-Rodriguez, C Ligeiro, FA Rao, A Goldfeld, AE AF Esensten, JH Tsytsykova, AV Lopez-Rodriguez, C Ligeiro, FA Rao, A Goldfeld, AE TI NFAT5 binds to the TNF promoter distinctly from NFATp, c, 3 and 4, and activates TNF transcription during hypertonic stress alone SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; T-CELL-ACTIVATION; GENE-EXPRESSION; HYPEROSMOTIC STRESS; SIGNALING PATHWAYS; OSMOTIC-STRESS; PROTEIN; ELEMENT; LIPOPOLYSACCHARIDE; IDENTIFICATION AB Tumor necrosis factor (TNF) is a pro-inflammatory cytokine that plays an important role in a variety of infectious and autoimmune disorders. Its transcription is regulated in a stimulus- and cell-type-specific manner via the recruitment of distinct DNA/activator complexes forming secondary structures or enhanceosomes. NFATp, a member of the nuclear factor of activated T cells (NFAT) family of transcription factors, plays a critical role in TNF gene regulation under a variety of conditions. In this study, we show that NFAT5, the most recently described NFAT family member, binds to the TNF promoter in a manner distinct from other NFAT proteins and is a key mediator in the activation of TNF gene transcription during hypertonic stress alone. C1 Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Dept Pathol, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org RI Lopez-Rodriguez, C/G-4482-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406 FU NCI NIH HHS [CA42471, R01 CA042471, R37 CA042471]; NIGMS NIH HHS [GM056492, R01 GM056492] NR 37 TC 35 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 12 BP 3845 EP 3854 DI 10.1093/nar/gki701 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 948OK UT WOS:000230725400023 PM 16027109 ER PT J AU Suswam, EA Li, YY Mahtani, H King, PH AF Suswam, EA Li, YY Mahtani, H King, PH TI Novel DNA-binding properties of the RNA-binding protein TIAR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; MAMMALIAN STRESS GRANULES; TUMOR-NECROSIS-FACTOR; FAR UPSTREAM ELEMENT; MESSENGER-RNA; TELOMERIC DNA; SPLICE-SITE; CRYSTAL-STRUCTURE; STABILITY FACTOR; POLYMERASE-II AB TIA-1 related protein binds avidly to uridine-rich elements in mRNA and pre-mRNAs of a wide range of genes, including interleukin (IL)-8 and vascular endothelial growth factor (VEGF). The protein has diverse regulatory roles, which in part depend on the locus of binding within the transcript, including translational control, splicing and apoptosis. Here, we observed selective and potent inhibition of TIAR-RNP complex formation with IL-8 and VEGF 3'-untranslated regions (3'-UTRs) using thymidine-rich deoxyoligonucleotide (ODN) sequences derived from the VEFG 3'-UTR. We show by ultraviolet crosslinking and electrophoretic mobility shift assays that TIAR can bind directly to single-stranded, thymidine-rich ODNs but not to double-stranded ODNs containing the same sequence. TIAR had a nearly 6-fold greater affinity for DNA than RNA (K(d app=)1.6x10(-9) M versus 9.4 x 10(-9) M). Truncation of TIAR indicated that the high affinity DNA-binding site overlaps with the RNA-binding site involving RNA recognition motif 2 (RRM2). However, RRM1 alone could also bind to DNA. Finally, we show that TIAR can be displaced from single-stranded DNA by active transcription through the binding site. These results provide a potential mechanism by which TIAR can shuttle between RNA and DNA ligands. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35295 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35295 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35295 USA. RP King, PH (reprint author), Univ Alabama, Dept Neurol, Birmingham, AL 35295 USA. EM pking@uab.edu NR 60 TC 39 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 14 BP 4507 EP 4518 DI 10.1093/nar/gki763 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 957ID UT WOS:000231362600018 PM 16091628 ER PT J AU Ichida, JK Horhota, A Zou, KY McLaughlin, LW Szostak, JW AF Ichida, JK Horhota, A Zou, KY McLaughlin, LW Szostak, JW TI High fidelity TNA synthesis by therminator polymerase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID AQUATICUS DNA-POLYMERASE; NUCLEIC-ACID STRUCTURE; DIRECTED EVOLUTION; CHEMICAL ETIOLOGY; SUGAR RECOGNITION; CRYSTAL-STRUCTURE; TEMPLATE; ARCHAEON; SYSTEM; DUPLEX AB Therminator DNA polymerase is an efficient DNA-dependent TNA polymerase capable of polymerizing TNA oligomers of at least 80 nt in length. In order for Therminator to be useful for the in vitro selection of functional TNA sequences, its TNA synthesis fidelity must be high enough to preserve successful sequences. We used sequencing to examine the fidelity of Therminator-catalyzed TNA synthesis at different temperatures, incubation times, tNTP ratios and primer/template combinations. TNA synthesis by Therminator exhibits high fidelity under optimal conditions; the observed fidelity is sufficient to allow in vitro selection with TNA libraries of at least 200 nt in length. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NIGMS NIH HHS [GM053936, GM067986, R01 GM053936, R01 GM067986] NR 23 TC 49 Z9 49 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 16 BP 5219 EP 5225 DI 10.1093/nar/gki840 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 970AR UT WOS:000232278100027 PM 16157867 ER PT J AU Shin, JT Priest, JR Ovcharenko, I Ronco, A Moore, RK Burns, CG MacRae, CA AF Shin, JT Priest, JR Ovcharenko, I Ronco, A Moore, RK Burns, CG MacRae, CA TI Human-zebrafish non-coding conserved elements act in vivo to regulate transcription SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GERM-LINE TRANSMISSION; TRANSGENIC ZEBRAFISH; GENE DESERTS; EXPRESSION; PROMOTER; SEQUENCES; GENOME; EVOLUTION; EMBRYOS; REGION AB Whole genome comparisons of distantly related species effectively predict biologically important sequences-core genes and cis-acting regulatory elements (REs)-but require experimentation to verify biological activity. To examine the efficacy of comparative genomics in identification of active REs from anonymous, non-coding (NC) sequences, we generated a novel alignment of the human and draft zebrafish genomes, and contrasted this set to existing human and fugu datasets. We tested the transcriptional regulatory potential of candidate sequences using two in vivo assays. Strict selection of non-genic elements which are deeply conserved in vertebrate evolution identifies 1744 core vertebrate REs in human and two fish genomes. We tested 16 elements in vivo for cis-acting gene regulatory properties using zebrafish transient transgenesis and found that 10 (63%) strongly modulate tissue-specific expression of a green fluorescent protein reporter vector. We also report a novel quantitative enhancer assay with potential for increased throughput based on normalized luciferase activity in vivo. This complementary system identified 11 (69%; including 9 of 10 GFP-confirmed elements) with cis-acting function. Together, these data support the utility of comparative genomics of distantly related vertebrate species to identify REs and provide a scaleable, in vivo quantitative assay to define functional activity of candidate REs. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Lawrence Berkeley Lab, Gen Div, Berkeley, CA 94720 USA. DOE Joint Gen Inst, Walnut Creek, CA 94598 USA. Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. RP Shin, JT (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. EM jshin1@partners.org; cmacrae@partners.org FU NHLBI NIH HHS [R25 HL088728, 5T32HL007208, HL88728, K08 HL068711, R24HL70580, T32 HL007208]; NIA NIH HHS [K01 AG023562]; NIGMS NIH HHS [R21 GM075946] NR 35 TC 50 Z9 51 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 17 BP 5437 EP 5445 DI 10.1093/nar/gki853 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974LS UT WOS:000232593700016 PM 16179648 ER PT J AU Plummer, KA Carothers, JM Yoshimura, M Szostak, JW Verdine, GL AF Plummer, KA Carothers, JM Yoshimura, M Szostak, JW Verdine, GL TI In vitro selection of RNA aptamers against a composite small molecule-protein surface SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; LIGANDS; SPECIFICITY; DIMERIZERS; BINDS; BASE AB A particularly challenging problem in chemical biology entails developing systems for modulating the activity of RNA using small molecules. One promising new approach towards this problem exploits the phenomenon of 'surface borrowing,' in which the small molecule is presented to the RNA in complex with a protein, thereby expanding the overall surface area available for interaction with RNA. To extend the utility of surface borrowing to include potential applications in synthetic biology, we set out to create an 'orthogonal' RNA-targeting system, one in which all components are foreign to the cell. Here we report the identification of small RNA modules selected in vitro to bind a surface-engineered protein, but only when the two macromolecules are bound to a synthetic bifunctional small molecule. C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM verdine@chemistry.harvard.edu FU NIGMS NIH HHS [GM53936, R01 GM044853, R01 GM053936] NR 24 TC 10 Z9 10 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 17 BP 5602 EP 5610 DI 10.1093/nar/gki867 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 974LS UT WOS:000232593700032 PM 16199752 ER PT J AU Read, ML Singh, S Ahmed, Z Stevenson, M Briggs, SS Oupicky, D Barrett, LB Spice, R Kendall, M Berry, M Preece, JA Logan, A Seymour, LW AF Read, ML Singh, S Ahmed, Z Stevenson, M Briggs, SS Oupicky, D Barrett, LB Spice, R Kendall, M Berry, M Preece, JA Logan, A Seymour, LW TI A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IN-VITRO CYTOTOXICITY; SMALL INTERFERING RNA; GENE DELIVERY; MOLECULAR-WEIGHT; MAMMALIAN-CELLS; DNA DELIVERY; LINEAR POLYETHYLENIMINE; VIVO DISTRIBUTION; DEPENDENT FUSION; HIGHLY EFFICIENT AB Synthetic vectors based on reducible polycations consisting of histidine and polylysine residues ( HIS RPCs) were evaluated for their ability to deliver nucleic acids. Initial experiments showed that RPC-based vectors with at least 70% histidine content mediated efficient levels of gene transfer without requirement for the endosomolytic agent chloroquine. Significant gene transfer was observed in a range of cell types achieving up to a 5-fold increase in the percentage of transfected cells compared to 25 kDa PEI, a gold standard synthetic vector. In contrast to 25 kDa PEI, HIS RPCs also mediated efficient transfer of other nucleic acids, including mRNA encoding green fluorescent protein in PC-3 cells and siRNA directed against the neurotrophin receptor p75(NTR) in post-mitotic cultures of rat dorsal root ganglion cell neurons. Experiments to elevate intracellular glutathione and linear profiling of cell images captured by multiphoton fluorescent microscopy highlighted that parameters such as the molecular weight and rate of cleavage of HIS RPCs were important factors in determining transfection activity. Altogether, these results demonstrate that HIS RPCs represent a novel and versatile type of vector that can be used for efficient cytoplasmic delivery of a broad range of nucleic acids. This should enable different or a combination of therapeutic strategies to be evaluated using a single type of polycation-based vector. C1 Univ Birmingham, Dept Med, Mol Neurosci Grp, Birmingham B15 2TT, W Midlands, England. Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England. Univ Oxford, Dept Clin Pharmacol, Oxford OX2 6HE, England. Wayne State Univ, Dept Pharmaceut Sci, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02139 USA. Univ Oxford, Dept Engn Sci, Oxford OX1 3PJ, England. RP Read, ML (reprint author), Univ Birmingham, Dept Med, Mol Neurosci Grp, Birmingham B15 2TT, W Midlands, England. EM mread@globalnet.co.uk RI Briggs, Simon/C-2961-2009; Stevenson, Mark/C-3745-2009; Read, Martin/A-3505-2012 OI Read, Martin/0000-0001-8918-4333 FU Biotechnology and Biological Sciences Research Council [BB/C515820/1] NR 54 TC 173 Z9 178 U1 2 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 9 AR e86 DI 10.1093/nar/gni085 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932HK UT WOS:000229544600007 PM 15914665 ER PT S AU Kang, JX AF Kang, JX BE Simopoulos, AP TI Balance of omega-6/omega-3 essential fatty acids is important for health SO Nutrition and Fitness: Mental Health, Aging, and the Implementation of a Healthy Diet and Physical Activity Lifestyle SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 5th International Conference on Nutrition and Fitness CY JUN 09-12, 2004 CL Athens, GREECE ID ADENOVIRAL GENE-TRANSFER; NEURONAL APOPTOSIS; BREAST-CANCER; DESATURASE; CELLS C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, 149-13th St,Room 4433, Boston, MA 02129 USA. NR 15 TC 10 Z9 12 U1 1 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7945-4 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2005 VL 95 BP 93 EP 102 DI 10.1159/000088276 PG 10 WC Nutrition & Dietetics; Sport Sciences SC Nutrition & Dietetics; Sport Sciences GA BDJ72 UT WOS:000233859400011 PM 16151274 ER PT S AU Leaf, A Kang, JX Xiao, YF AF Leaf, A Kang, JX Xiao, YF BE Simopoulos, AP TI Ornega-3 fatty acids and ventricular arrhythmias SO Nutrition and Fitness: Obesity, the Metabolic Syndrome, Cardiovascular Disease, and Cancer SE WORLD REVIEW OF NUTRITION AND DIETETICS LA English DT Proceedings Paper CT 5th International Conference on Nutrition and Fitness CY JUN 09-12, 2004 CL Athens, GREECE ID RAT CARDIAC MYOCYTES; NA+ CHANNELS; PREVENTION; CURRENTS; TRIAL; DEATH C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, East Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL 62284, HL62154]; NIDDK NIH HHS [DK38165] NR 11 TC 7 Z9 8 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 3-8055-7944-6 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2005 VL 94 BP 129 EP 138 DI 10.1159/000088226 PG 10 WC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Sport Sciences; Peripheral Vascular Disease SC Oncology; Public, Environmental & Occupational Health; Nutrition & Dietetics; Sport Sciences; Cardiovascular System & Cardiology GA BDN14 UT WOS:000234406800016 PM 16145258 ER PT J AU Becker, AE Gilman, SE Burwell, RA AF Becker, AE Gilman, SE Burwell, RA TI Changes in prevalence of overweight and in body image among Fijian women between 1989 and 1998 SO OBESITY RESEARCH LA English DT Article DE Fiji; social change; modernization; body image ID ETHNIC-DIFFERENCES; DIABETES-MELLITUS; OBESITY EPIDEMIC; DIETARY PATTERNS; UNITED-STATES; RISK-FACTORS; SIZE; PERCEPTIONS; POLYMORPHISM; POLYNESIANS AB Objective: To investigate changes in prevalence of overweight and obesity and in body image among ethnic Fijian women in Fiji during a period of rapid social change and the relationship between changes in body image and BMI. Research Methods and Procedures: The study design was a multiwave cohort study of BMI in a traditional Fijian village over a 9.5-year period from 1989 to 1998. Cohorts were identified in 1989 (n = 53) and in 1998 (n = 50). Selection criteria included Fijian ethnicity, female gender, age of at least 18 years, and residence in a specific coastal Fijian village in 1989 and 1998, respectively. Assessments consisted of measurement of height and weight, collection of demographic data by written survey, and administration of the Nadroga Language Body Image Questionnaire. Results: The prevalence of overweight and obesity was significantly different between the cohorts, increasing from 60% in 1989 to 84% in 1998 (p = 0.014). In addition, the age-adjusted mean BMI was significantly higher in 1998 compared with 1989 0.011). Finally, there were significant between-cohort differences in multiple measures of body image, which were mostly independent of BMI. Discussion: At 84%, the prevalence of overweight and obesity in this community sample of Fijian women is among the highest in the world. The dramatically increased prevalence over the 9.5-year period studied corresponds with rapid social change in Fiji and significant shifts in prevailing traditional attitudes toward body shape. C1 Massachusetts Gen Hosp, Adult Eating & Weight Disorders Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Society Human Dev & Hlth, Boston, MA 02115 USA. Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI USA. Univ Denver, Dept Psychol, Denver, CO 80208 USA. RP Becker, AE (reprint author), Massachusetts Gen Hosp, Adult Eating & Weight Disorders Program, Dept Psychiat, WAC 816-15 Parkman St, Boston, MA 02114 USA. EM abecker@partners.org RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 NR 50 TC 40 Z9 41 U1 2 U2 7 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JAN PY 2005 VL 13 IS 1 BP 110 EP 117 DI 10.1038/oby.2005.14 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 907BG UT WOS:000227689200014 PM 15761169 ER PT J AU Sonnenberg, L Pencina, M Kimokoti, R Quatromoni, P Nam, BH D'Agostino, R Meigs, JB Ordovas, J Cobain, M Millen, B AF Sonnenberg, L Pencina, M Kimokoti, R Quatromoni, P Nam, BH D'Agostino, R Meigs, JB Ordovas, J Cobain, M Millen, B TI Dietary patterns and the metabolic syndrome in obese and non-obese Framingham women SO OBESITY RESEARCH LA English DT Article DE dietary patterns; risk factor; diabetes; genetic phenotype; cardiovascular disease ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; EDUCATION-PROGRAM; NUTRITION; ADULTS; POLYMORPHISM; RISK AB Objectives: To examine the relationship between habitual dietary patterns and the metabolic syndrome (MetS) in women and to identify foci for preventive nutrition interventions. Research Methods and Procedures: Dietary patterns, nutrient intake, cardiovascular disease (CVD), and MetS risk factors were characterized in 1615 Framingham Offspring-Spouse Study (FOS) women. Dietary pattern subgroups were compared for MetS prevalence and CVD risk factor status using logistic regression and analysis of covariance. Analyses were performed overall in women and stratified on obesity status; multivariate models controlled for age, apolipoprotein E (APOE) genotypes, and CVD risk factors. Results: Food and nutrient profiles and overall nutritional risk of five non-overlapping habitual dietary patterns of women were identified including Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calories. Rates of hypertension and low high-density lipoprotein levels were high in non-obese women, but individual MetS risk factor levels were substantially increased in obese women. Overall MetS risk varied by dietary pattern and obesity status, independently of APOE and CVD risk factors. Compared with obese or non-obese women and women overall with other dietary patterns, MetS was highest in those with the Empty Calorie pattern (contrast p value: p < 0.05). Discussion: This research shows the independent relationship between habitual dietary patterns and MetS risk in FOS women and the influence of obesity status. High overall MetS risk and the varying prevalence of individual MetS risk factors in female subgroups emphasize the importance of preventive nutrition interventions and suggest potential benefits of targeted behavior change in both obese and non-obese women by dietary pattern. C1 Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Nutr & Food Serv, Ambulatory Nutr Serv, Boston, MA 02114 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Sargent Coll Hlth & Rehabil Sci, Dept Hlth Sci, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Lipid Metab Lab, USDA,Human Nurt Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Med, Grad Med Sci Div, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Sociomed Sci, Boston, MA 02118 USA. RP Millen, B (reprint author), Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, 715 Albany St,Talbot 263 W, Boston, MA 02118 USA. EM bmillen@bu.edu OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-25195, R01-HL-54776, R01-HL-60,700] NR 46 TC 58 Z9 61 U1 1 U2 11 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD JAN PY 2005 VL 13 IS 1 BP 153 EP 162 DI 10.1038/oby.2005.20 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 907BG UT WOS:000227689200020 PM 15761175 ER PT J AU Prigerson, HG Maciejewski, PK AF Prigerson, HG Maciejewski, PK TI A call for sound empirical testing and evaluation of criteria for Complicated Grief proposed for DSM-V SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Article ID BEREAVEMENT-RELATED DEPRESSION; TRAUMATIC GRIEF; DISORDER DISTINCT; SYMPTOMS; HEALTH; REPLICATION; INVENTORY; DISTRESS; VALIDITY; OUTCOMES AB The empirical testing of diagnostic criteria for Complicated Grief (CG) by autonomous investigators is a welcome development. Cross-validation studies are essential to an impartial evaluation of diagnostic criteria for CG proposed for inclusion in the DSM-V. Nevertheless, the review of evidence to confirm or disconfirm the diagnostic validity of the proposed CG criteria requires a fair,unbiased, and relevant examination of the data. It is our view that Hogan, Worden, and Schmidt's (2003-2004) "An Empirical Study of the Complicated Grief Disorder Criteria" (see Table 1) fails to meet these standards. Hogan et a]. test for the independence between: a) separation distress and traumatic distress symptoms, b) CG and depressive symptoms, c) CG symptoms and presumably "normal" symptoms of grief. Testing for the independence of these constructs is a red herring. Issues central to the validity and reliability of a CG diagnosis should focus on the ability of the symptoms to identify the small number of bereaved persons with enduring and acutely distressing grief that is associated with significant dysfunction. Despite asking the wrong questions, the basic results remain consistent with claims that we have made all along (e.g., that CG symptoms are unidimensional; that more than half the variance in CG symptoms cannot be explained by depressive symptoms; that CG symptoms distinguish themselves from normal grief symptoms with respect to their intensity and chronicity and the prediction of morbidity). There is little doubt of the need for more empirical work to evaluate the reliability, validity, sensitivity, specificity, and diagnostic efficiency of criteria proposed for CG. It is our hope that the call will be heard by investigators who will test issues relevant to the creation of a sound CG diagnosis. C1 Harvard Univ, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, 440 Shields Warren Bldg,44 Binney St, Boston, MA 02115 USA. EM Holly_Prigerson@dfci.Harvard.edu NR 27 TC 30 Z9 30 U1 2 U2 10 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2005 VL 52 IS 1 BP 9 EP 19 PG 11 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 042HF UT WOS:000237518100002 ER PT J AU Prigerson, HG Vanderwerker, LC AF Prigerson, HG Vanderwerker, LC TI Final remarks SO OMEGA-JOURNAL OF DEATH AND DYING LA English DT Editorial Material C1 Harvard Univ, Boston, MA 02115 USA. RP Prigerson, HG (reprint author), Dana Farber Canc Inst, 440 Shields Warren Bldg,44 Binney St, Boston, MA 02115 USA. EM Holly-Prigerson@dfci.Harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, PO BOX 337, AMITYVILLE, NY 11701 USA SN 0030-2228 J9 OMEGA-J DEATH DYING JI Omega-J. Death Dying PY 2005 VL 52 IS 1 BP 91 EP 94 PG 4 WC Psychology, Multidisciplinary; Social Sciences, Biomedical SC Psychology; Biomedical Social Sciences GA 042HF UT WOS:000237518100009 ER PT J AU Posner, MR AF Posner, MR TI Paradigm shift in the treatment of head and neck cancer: The role of neoadjuvant chemotherapy SO ONCOLOGIST LA English DT Article DE head and neck cancer; chemotherapy; neoadjuvant; docetaxel; paclitaxel ID SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; LOCALLY ADVANCED HEAD; STAGE OROPHARYNX CARCINOMA; ADVANCED LARYNGEAL-CANCER; 10-YEAR FOLLOW-UP; INDUCTION CHEMOTHERAPY; RANDOMIZED-TRIAL; CONCOMITANT CHEMORADIOTHERAPY; ORGAN PRESERVATION AB Chemotherapy is an integral component of the management of patients with locally advanced head and neck cancer, though the optimal use of chemotherapy remains to be defined. The combination of a platinum agent and 5-fluorouracil has been used as the standard neoadjuvant treatment and has been shown to permit organ preservation in operable patients and improve long-term survival outcomes in operable and inoperable patients. Recently, the addition of a taxane, docetaxel or paclitaxel, to standard platinum plus 5-fluorouracil induction chemotherapy has been shown to further improve response rates and survival outcomes. Phase III data are emerging to support combinations of docetaxel or paclitaxel with a platinum plus 5-fluorouracil as a new, more effective and less toxic standard for neoadjuvant chemotherapy. Sequential treatment regimens, incorporating a combination of induction chemotherapy and chemoradiation, are also under study in efforts to further improve long-term survival outcomes. Induction regimens incorporating docetaxel or paclitaxel with a platinum plus 5-fluorouracil are under evaluation in this setting. Randomized trials comparing a sequential treatment approach with standard therapies are also being undertaken and will likely define a new treatment paradigm for patients with locally advanced head and neck cancer. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St SW,Suite 430, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu NR 55 TC 37 Z9 39 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 PY 2005 VL 10 SU 3 BP 11 EP 19 DI 10.1634/theoncologist.10-90003-11 PG 9 WC Oncology SC Oncology GA 999VR UT WOS:000234419400002 PM 16368867 ER PT J AU Oh, WK AF Oh, WK TI High-risk localized prostate cancer: Integrating chemotherapy SO ONCOLOGIST LA English DT Article; Proceedings Paper CT Conference on Reaching for a Cure - New Horizons For Early Stage Neoplastic Disease CY MAY 13-17, 2005 CL Orland, FL DE prostate cancer; high risk; adjuvant; neoadjuvant; docetaxel ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; BREAST-CANCER; DOCETAXEL; MITOXANTRONE; PREDNISONE AB Docetaxel (Taxotere((R)); sanofi-aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharmaus.com) is the first agent to significantly extend survival in hormone-refractory prostate cancer. Because agents active in advanced cancers tend to be beneficial in earlier stage disease, docetaxel is now to be assessed, along with hormonal therapy, in the adjuvant setting among patients whose localized prostate cancer has features that put them at particular risk for recurrence and cancer-specific mortality. Data from a pilot study suggest that neoadjuvant treatment with docetaxel may be appropriate for selected high-risk patients and that such treatment can be undertaken without increasing surgical morbidity. Gene-expression profiling of tissue before and after docetaxel treatment is providing further insight into its effects. A randomized trial, conducted by the Cancer and Leukemia Group B, will evaluate neoadjuvant docetaxel in high-risk patients, whereby patients will be randomized to either immediate radical prostatectomy or surgery preceded by hormonal therapy plus docetaxel. Another large randomized trial will be evaluating the effect of adjuvant hormonal therapy with or without docetaxel in high-risk men after radical prostatectomy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 18 TC 9 Z9 9 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 PY 2005 VL 10 SU 2 BP 18 EP 22 DI 10.1634/theoncologist.10-90002-18 PG 5 WC Oncology SC Oncology GA 988EB UT WOS:000233573300004 PM 16272455 ER PT J AU Mukohara, T Civiello, G Johnsona, BE Janne, PA AF Mukohara, T Civiello, G Johnsona, BE Janne, PA TI Therapeutic targeting of multiple signaling pathways in malignant pleural mesothelioma SO ONCOLOGY LA English DT Article DE malignant mesothelioma; epidermal growth factor receptor; signal transduction ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CANCER CELL-LINES; LUNG-CANCER; ZD1839 IRESSA; TUMOR-SUPPRESSOR; FACTOR-ALPHA; IN-VITRO; EXPRESSION; PROGRESSION AB The majority of malignant pleural mesotheliomas (MPMs) aberrantly express the epidermal growth factor receptor (ErbB1). We examined the efficacy of GW572016 (lapatinib), a dual inhibitor of ErbB1/ErbB2 with a panel of 10 MPM cell lines. Two of the 10 MPM cell lines, H2373 and H2452, underwent G1/S cell cycle arrest and growth inhibition with an IC50 Of 1 mu M and 0.8 mu M, respectively. There was no relationship between the presence or the amount of ErbB1, phospho-ErbB1, phospho-ErbB2, ErbB3, ErbB4, phospho-Akt, and Akt or the ability of lapatinib to inhibit phospho-ErbB1 in these cell lines compared to those that did not respond to lapatinib. The sensitive cell lines had a time-dependent decrease in phospho-Akt and/or ERK1/2, and an increase in p27 and when treated with lapatinib. The combination of lapatinib with U0126, LY294002 or rapamycin caused greater growth inhibition than either drug alone in the sensitive cell lines while this did not occur in the resistant cell lines. Our findings suggest that ErbB1 alone is a therapeutic target for the minority of mesotheliomas and that combining ErbB1 inhibitors with signal transduction inhibitors in mesothelioma will enhance their effectiveness. Furthermore, combinations of growth factor and signal transduction inhibitors may be needed to inhibit the growth of the majority of MPM cell lines, and therefore patients with MPM. Copyright (C) 2005 S. Karger AG, Basel. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU NCI NIH HHS [1K12CA87723-01] NR 40 TC 17 Z9 19 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY-BASEL JI Oncology PY 2005 VL 68 IS 4-6 BP 500 EP 510 DI 10.1159/000086994 PG 11 WC Oncology SC Oncology GA 958SQ UT WOS:000231468900028 PM 16020981 ER PT J AU Radwin, LE Washko, M Suchy, KA Tyman, K AF Radwin, LE Washko, M Suchy, KA Tyman, K TI Development and pilot testing of four desired health outcomes scales SO ONCOLOGY NURSING FORUM LA English DT Article ID QUALITY; CARE; PERFORMANCE AB Purpose/Objectives: To develop and pilot test scales to measure desired health outcomes hypothesized to result from high-quality cancer nursing care: Fortitude Scale, Trust in Nurses Scale, Cancer Patient Optimism Scale, and Authentic Self-Representation Scale. Design: Instrument development. Setting: Community cancer support organization. Sample: 66 recently treated patients with cancer who attended a cancer support organization workshop. The sample was predominately white, middle-aged, well-educated females. Methods: Items for each scale were generated from qualitative data and the literature. The scales' properties were evaluated using expert panel assessment of content validity, cognitive interviews of patients with cancer, and reliability and validity testing of each scale with the Multitrait/Multi-Item Analysis Program-Revised (MAP-R) statistical program. Findings: Participant responses to the four scales did not include the lowest possible score. Responses yielded evidence of adequate Cronbach's alpha internal consistency reliability for each scale: 0.81 for the Fortitude Scale; 0.81 for Trust in Nurses Scale, 0.75 for Cancer Patient Optimism Scale, and 0.71 for Authentic Self-Representation Scale. The MAP-R statistics yielded evidence of acceptable convergent validity and discriminant validity. Conclusions: The data provided preliminary evidence of acceptable psychometric properties for four scales designed to measure desired outcomes of cancer nursing care. Support was found for careful use of scales. Further psychometric testing with large samples is recommended. Implications for Nursing: These scales represent an initial effort toward providing measures of the desired health outcomes that patients with cancer attributed to high-quality cancer nursing care. C1 Univ Massachusetts, Dept Nursing, Boston, MA 02125 USA. Univ Massachusetts, Dept Gerontol, Boston, MA 02125 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Radwin, LE (reprint author), Univ Massachusetts, Dept Nursing, Boston, MA 02125 USA. EM radwin@umb.edu FU AHRQ HHS [K08 HS 11625] NR 22 TC 13 Z9 13 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2005 VL 32 IS 1 BP 92 EP 96 DI 10.1188/05.ONF.92-96 PG 5 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300016 PM 15660147 ER PT J AU Cooley, M Sarna, L Danao, L Brown, J Chernecky, C Padilla, G AF Cooley, M Sarna, L Danao, L Brown, J Chernecky, C Padilla, G TI Patterns of smoking in women with lung cancer. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2005 VL 32 IS 1 BP 153 EP 153 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300047 ER PT J AU Fonteyn, M Vettese, M Bauer-Wu, S AF Fonteyn, M Vettese, M Bauer-Wu, S TI Improving intercoder agreement in qualitative analysis. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 JAN PY 2005 VL 32 IS 1 BP 158 EP 159 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300064 ER PT J AU McDermott, K Roper, K Cooley, ME Boyd, K Coakley, C AF McDermott, K Roper, K Cooley, ME Boyd, K Coakley, C TI Quality of life in adults with Hodgkins disease: State of the science. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Massachusetts, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2005 VL 32 IS 1 BP 167 EP 167 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300091 ER PT J AU Hanser, S Bauer-Wu, S Kubicek, L Healey, M Bunnell, C Manola, J AF Hanser, S Bauer-Wu, S Kubicek, L Healey, M Bunnell, C Manola, J TI Effects of a music therapy intervention for women with metastatic breast cancer SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Berklee Coll Mus, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 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 JAN PY 2005 VL 32 IS 1 BP 185 EP 186 PG 2 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300152 ER PT J AU Chen, TC Bhatia, LS Walton, DS AF Chen, TC Bhatia, LS Walton, DS TI Complications of pediatric lensectomy in 193 eyes SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 15-18, 2003 CL ANAHEIM, CA SP Amer Acad Ophthalmol ID CONGENITAL CATARACT-SURGERY; INFANTILE CATARACTS; GLAUCOMA; VITRECTOMY; PREVALENCE; CHILDREN AB BACKGROUND AND OBJECTIVE: To better define late complications and long-term visual outcomes associated with lensectomy surgery for pediatric cataracts. PATIENTS AND METHODS: Retrospective review of all patients seen by a pediatric ophthalmologist from 1970 to 2002. Patients were seen at a university-based clinical practice setting. This study defines the incidence of late post-lensectomy complications. Final long-term visual acuities were correlated with specific surgical complications and ocular and systemic anomalies. RESULTS: There were 193 eyes of 138 patients who had lensectomy for pediatric cataracts. The average follow-up time was 10.8 +/- 6.7 years (range, 3 months to 31.3 years). The most common postoperative complication was aphakic glaucoma (20.2%) at an average of 3.4 +/- 3.7 years after lensectomy surgery. At last follow-up, the median visual acuity was 20/40 in eyes without complications and 20/80 in eyes with complications. CONCLUSIONS: Aphakic glaucoma was the most common postoperative complication (20.2%). Most eyes with associated ocular and systemic anomalies and postoperative complications have poorer visual outcomes. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. NR 30 TC 22 Z9 24 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1082-3069 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD JAN-FEB PY 2005 VL 36 IS 1 BP 6 EP 13 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 887SC UT WOS:000226324800001 PM 15688966 ER PT J AU Arroyo, JG Bula, DV Lui, Y Dong, FC AF Arroyo, JG Bula, DV Lui, Y Dong, FC TI Retinal biopsy techniques for the removal of retinal tissue fragments SO OPHTHALMIC SURGERY LASERS & IMAGING LA English DT Article ID DETACHMENT AB Because retinal tissue normally excised during retinal reattachment repair is usually discarded, safe methods for the removal of retinal tissue from the eye were developed. Two methods are described for the removal of retinal tissue fragments otherwise discarded during vitrectomy for retinal detachment repair: (1) the removal of small oval pieces of retinal tissue associated with horseshoe retinal tears and (2) the removal of larger rectangular pieces of retinal tissue associated with relaxing retinotomies or giant retinal tears. These methods provide the retinal surgeon with some simple and safe methods for the extraction of retinal tissue fragments that would otherwise be discarded at the end of surgery. C1 Beth Israel Deaconess Med Ctr, Retina Serv, Boston, MA 02215 USA. Brigham & Womens Hosp, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Retina Serv, Shapiro 5,330 Brookline Ave, Boston, MA 02215 USA. NR 5 TC 5 Z9 5 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1082-3069 J9 OPHTHAL SURG LAS IM JI Ophthalmic Surg. Lasers Imaging PD JAN-FEB PY 2005 VL 36 IS 1 BP 76 EP 78 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 887SC UT WOS:000226324800011 PM 15688976 ER PT S AU Castano, AP Hamblin, MR AF Castano, AP Hamblin, MR BE Jacques, SL Roach, WP TI Anti-tumor immunity generated by photodynamic therapy in a metastatic murine tumor model SO Optical Interactions with Tissue and Cells XVI SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Interactions with Tissue and Cells XVI CY JAN 24-26, 2005 CL San Jose, CA SP SPIE DE photodynamic therapy; photosensitizer; cyclophosphamide; regulatory T cells (CD25(+)CD4(+)); antitumor immunity ID REGULATORY T-CELLS; HEAT-SHOCK PROTEINS; LYMPH-NODES; CYCLOPHOSPHAMIDE; IMMUNOTHERAPY; IMMUNOREGULATION; REJECTION; DEPLETION; VACCINES; SUBSETS AB Photodynamic therapy (PDT) is a modality for the treatment of cancer involving excitation of photosensitizers; with harmless visible light producing reactive oxygen species. The major biological effects of PDT are apoptosis of tumor cells, destruction of the blood supply and activation of the immune system. The objective of this study is to compare in an animal model of metastatic cancer, PDT alone and PDT combined with low-dose cyclophosphamide (CY). Since the tumor we used is highly metastatic, it is necessary to generate anti-tumor immunity using PDT to both cure the primary tumor and prevent death from metastasis. This immunity may be potentiated by low dose CY. In our model we used J774 cells (a Balb/c reticulum cell sarcoma line with the characteristics of macrophages) and the following PDT regimen: benzoporphyrin derivative monoacid ring A (BPD, 2mg/kg injected IV followed after 15 min by 150 j/cm(2) of 690-nm light). CY (50 mg/kg i.p.) was injected 48 hours before light delivery. BPD-PDT led to complete regression of the primary tumor in more than half the mice but no permanent cures were obtained. BPD-PDT in combination with CY led to 60% permanent cures. CY alone gave no permanent cures but did provide a survival advantage. To probe permanent immunity cured animals were rechallenged with the same tumor cell line and the tumors were rejected in 71% of mice cured with BPD-PDT plus CY. We conclude that BPD-PDT in combination with CY gives best overall results and that this is attributable to immunological response activation in addition to PDT-mediated destruction of the tumor. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Castano, AP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 29 TC 3 Z9 4 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5669-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5695 BP 7 EP 16 DI 10.1117/12.589340 PG 10 WC Biophysics; Optics SC Biophysics; Optics GA BCH88 UT WOS:000229361500002 ER PT S AU Demidova, TN Hamblin, MR AF Demidova, TN Hamblin, MR BE Kessel, D TI Anthrax surrogate spores are destroyed by PDT mediated by phenothiazinium dyes. SO Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIV SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Methods for Tumor Treatment and Detection - Mechanisms and Techniques in Photodynamic Therapy XIV CY JAN 22-23, 2005 CL San Jose, CA SP SPIE DE photosensitizer; anthrax; spore; photodynamic therapy; toluidine blue; methylene blue; Bacillus species ID BACILLUS-SUBTILIS SPORES; PHOTODYNAMIC THERAPY; METHYLENE-BLUE; STAPHYLOCOCCUS-AUREUS; PHOTOBACTERICIDAL ACTIVITY; WOUND INFECTIONS; ESCHERICHIA-COLI; BACTERIAL-SPORES; MEGATERIUM SPORE; IN-VIVO AB Some Gram-positive bacteria (including the causative agent of anthrax - Bacillus anthracis) survive conditions of stress and starvation by producing dormant stage spores. The spore's multilayered capsule consists of inner and outer membranes, cortex, proteinaceous spore coat, and in some species an exosporium. These outer layers enclose dehydrated and condensed DNA, saturated with small, acid-soluble proteins. These protective structures make spores highly resistant to damage by heat, radiation, and commonly employed anti-bacterial agents. Previously Bacillus spores have been shown to be resistant to photodynamic inactivation (PDI) using dyes and light that easily destroy the corresponding vegetative bacteria, but recently we have discovered that they are susceptible to PDI Photoinactivation, however, is only possible if phenothiazinium dyes are used. Dimethylmethylene blue, methylene blue, new methylene blue and toluidine blue O are all effective photosensitizers. Alternative photosensitizers such as Rose Bengal, polylysine chlorin(e6) conjugate, a tricationic porphyrin and benzoporphyrin derivative are ineffective against spores even though they can easily kill vegetative cells. Spores of B. cereus and B. thuringiensis are most susceptible, B. subtilis and B. atrophaeus are also killed, while B. megaterium is resistant. Photoinactivation is most effective when excess dye is washed from the spores showing that the dye binds to the spores and that excess dye in solution can quench light delivery. The relatively mild conditions needed for spore killing could have applications for treating wounds contaminated by anthrax spores and for which conventional sporicides would have unacceptable tissue toxicity. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Wellman Labs Photomed, Boston, MA 02114 USA. RP Demidova, TN (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 54 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5663-2 J9 P SOC PHOTO-OPT INS PY 2005 VL 5689 BP 66 EP 77 DI 10.1117/12.589324 PG 12 WC Oncology; Optics SC Oncology; Optics GA BCF47 UT WOS:000229038400008 ER PT S AU Huppert, TJ Hoge, RD Franceschini, MA Boas, DA AF Huppert, TJ Hoge, RD Franceschini, MA Boas, DA BE Chance, B Alfano, RR Tromberg, BJ SevickMuraca, EM TI A spatial-temporal comparison of fMRI and NIRS hemodynamic responses to motor stimuli in adult humans SO Optical Tomography and Spectroscopy of Tissue VI SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue VI CY JAN 23-26, 2005 CL San Diego, CA SP SPIE DE near infrared spectroscopy; NIRS; fMRI; BOLD; spatial comparison ID NEAR-INFRARED SPECTROSCOPY; SENSORY STIMULATION; OPTICAL TOMOGRAPHY; BLOOD OXYGENATION; PHOTON MIGRATION; BRAIN ACTIVATION; IN-VIVO; TRANSPORT; TISSUES; MRI AB Near infrared spectroscopy (NIRS) has the ability to record, at high temporal resolution, hemodynamic changes within the brain during functional activity. Although alone, NIRS has a poorer spatial resolution compared to other imaging methods such as functional MRI (MRI), multi-modality approaches, which attempt to fuse the spatial resolution of MRI with the hemoglobin oxygenation information and temporal resolution of NIRS, show promise to yielding better insight into the hemodynamic and metabolic response of the functional brain in future research. However, paramount to the development of these multi-modality approaches, proper control experiments to validate. the correlation between NIRS and fMRI methods must be preformed. In this experiment, we have examined the spatial and temporal relationship between the NIRS measure of deoxy-hemoglobin and the FMRI blood oxygen level dependent (BOLD) signal. Here, we have modeled the propagation of light through realistic, tissue segmented, head models for each of five subjects. Using these sensitivity profiles, we predicted the measurement of deoxy-hemoglobin for each individual NIRS source-detector pair from the projection of the volume-wise fMRI BOLD changes, thus allowing a quantitative spatial and temporal comparison between NIRS and fMRI. We report a linear correlation of R = 0.73 (p < 2 x 10(-8)) between the spatial profiles between the NIRS measure of deoxy-hemoglobin and BOLD signal. We also report a temporal correlation of R = 0.88 (p < 9 x 10(-18)) between the region-of-interest averaged responses using the projected BOLD response. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Huppert, TJ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. NR 30 TC 4 Z9 4 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0302-9743 BN 0-8194-5667-5 J9 LECT NOTES COMPUT SC PY 2005 VL 5693 BP 191 EP 202 DI 10.1117/12.612143 PG 12 WC Engineering, Biomedical; Instruments & Instrumentation; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Engineering; Instruments & Instrumentation; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BCK39 UT WOS:000229735700025 ER PT J AU Gokhale, AS Haddad, RI Cavacini, LA Wirth, L Weeks, L Hallar, M Faucher, J Posner, MR AF Gokhale, AS Haddad, RI Cavacini, LA Wirth, L Weeks, L Hallar, M Faucher, J Posner, MR TI Serum concentrations of interleukin-8, vascular endothelial growth factor, and epidermal growth factor receptor in patients with squamous cell cancer of the head and neck SO ORAL ONCOLOGY LA English DT Article DE head and neck cancer; IL-8; VEGF; EGFR ID CLINICOPATHOLOGICAL FEATURES; CARCINOMA; EXPRESSION; PROGNOSIS AB Squamous cell cancer of the head and neck (SCCHN) is associated with production of pro-inflammatory and pro-angiogenic cytokines. We hypothesized that cytokine serum Levels will correlate with tumor volume and aggressiveness. We investigated interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in SCCHN. The patient population consisted of normal and irradiated controls: patients with newly diagnosed SCCHN, and patients with recurrent or metastatic disease. Pretreatment sera were studied by ELISA. Serum IL-8 levels, as opposed to VEGF or EGFR, were consistently elevated in patients with recurrent or metastatic disease. The differences in mean serum IL-8, compared to controls, were significant (p=0.02). Serum levels of IL-8 are consistently elevated in patients with recurrent or metastatic SCCHN and elevated levels may correlate with advanced or aggressive disease. Further, more intensive, study of IL-8 as a biomarker in SCCHN is warranted. (C) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program,Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Human Monoclonal Antibody Lab, Div Hematol Oncol, Dept Med, Boston, MA 02215 USA. RP Haddad, RI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program,Dept Adult Oncol, 44 Binney St,SW430G, Boston, MA 02115 USA. EM robert_haddad@dfci.harvard.edu NR 16 TC 42 Z9 43 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD JAN PY 2005 VL 41 IS 1 BP 70 EP 76 DI 10.1016/j.oraloncology.2004.06.005 PG 7 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 894RA UT WOS:000226808100010 PM 15598588 ER PT B AU Kaunitz, JD Tanaka, S Akiba, Y AF Kaunitz, JD Tanaka, S Akiba, Y BE Ishii, H Suematsu, M Tanishita, K Suzuki, H TI Gastroduodenal microcirculatory response to luminal acid SO ORGAN MICROCIRCULATION: A GATEWAY TO DIAGNOSITC AND THERAPEUTIC INTERVENTIONS SE KEIO UNIVERSITY INTERNATIONAL SYMPOSIA FOR LIFE SCIENCES AND MEDICINE LA English DT Proceedings Paper CT 14th Keio-University International Symposium for Life Sciences and Medicine CY DEC 11-13, 2003 CL Keio Univ, Tokyo, JAPAN SP Keio Univ Med Sci Fund HO Keio Univ DE stomach; esophagus; duodenum; vanilloid receptor; blood flow ID GENE-RELATED PEPTIDE; MUCOSAL BLOOD-FLOW; SENSING PATHWAYS; RAT DUODENUM; HYPEREMIC RESPONSE; VAGAL AFFERENTS; PROTECTION; ESOPHAGUS; SENSITIVITY; MECHANISMS AB The hyperemic response to luminal acid, a key protective mechanism for upper gastrointestinal mucosa, occurs by different mechanisms in the distal esophagus, stomach, and duodenum. The esophagus is a stratified squamous mucosa of high electrical resistance. Although luminal acid permeates only into the superficial epithelial layer, luminal acid induces protective mucosal hyperemia and clinical symptoms. The stomach has a well-studied micro circulatory response to luminal acid. Blood flow is believed to play a prominent role in mucosal protection, since the abolition of the hyperemic response to luminal acid is associated with enhanced mucosal injury susceptibility. Infusion of pentagastrin, mimicking the endogenous secretory gastric response to food, unmasked this hyperemic response in undamaged mucosa and activates neurons in the vagal nucleus. The duodenum is a leaky, low-resistance, columnar epithelium. Unlike the stomach, duodenal hyperemia is readily produced by perfusion with acidic luminal solutions. We further studied the afferent pathways involved with this hyperemic response. The vanilloid receptor (VR) antagonist capsazepine (CPZ) dose-dependently inhibited capsaicin-induced hyperemia. Capsazepine dose-dependently inhibited acid-induced hyperemia. The gastric and intestinal mucosae are richly innervated with VR. Each segment of the gastrointestinal tract exposed to gastric acid appears to have a unique protective mechanisms to which regulation of mucosal blood flow plays an important role. C1 Greater Los Angeles Vet Affairs Healthcare Syst, WLAVA Med Ctr, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, WLAVA Med Ctr, Los Angeles, CA 90073 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-22135-2 J9 KEIO U INT SYMP LIFE JI Keio Univ. Int. Symp. Life Sci. Med PY 2005 VL 13 BP 79 EP 88 PG 10 WC Engineering, Biomedical; Gastroenterology & Hepatology; Peripheral Vascular Disease SC Engineering; Gastroenterology & Hepatology; Cardiovascular System & Cardiology GA BBN74 UT WOS:000226302200010 ER PT B AU Takeuchi, T Zhang, LN Kaunitz, JD AF Takeuchi, T Zhang, LN Kaunitz, JD BE Ishii, H Suematsu, M Tanishita, K Suzuki, H TI Intracellular pH (pH(i)) measurement in rat duodenal epithelium in vivo using SNARF-1 SO ORGAN MICROCIRCULATION: A GATEWAY TO DIAGNOSITC AND THERAPEUTIC INTERVENTIONS SE KEIO UNIVERSITY INTERNATIONAL SYMPOSIA FOR LIFE SCIENCES AND MEDICINE LA English DT Proceedings Paper CT 14th Keio-University International Symposium for Life Sciences and Medicine CY DEC 11-13, 2003 CL Keio Univ, Tokyo, JAPAN SP Keio Univ Med Sci Fund HO Keio Univ DE SNARF-1; pH(i); duodenal epithelium; in vivo; acid C1 W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. RP Takeuchi, T (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Bldg 114,Suite 217, Los Angeles, CA 90073 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-22135-2 J9 KEIO U INT SYMP LIFE JI Keio Univ. Int. Symp. Life Sci. Med PY 2005 VL 13 BP 89 EP 91 PG 3 WC Engineering, Biomedical; Gastroenterology & Hepatology; Peripheral Vascular Disease SC Engineering; Gastroenterology & Hepatology; Cardiovascular System & Cardiology GA BBN74 UT WOS:000226302200011 ER PT B AU Fukumura, D AF Fukumura, D BE Ishii, H Suematsu, M Tanishita, K Suzuki, H TI Tumor angiogenesis regulated by gaseous molecules in tumor microenvironment: Oxygen, pH, and nitric oxide SO ORGAN MICROCIRCULATION: A GATEWAY TO DIAGNOSITC AND THERAPEUTIC INTERVENTIONS SE KEIO UNIVERSITY INTERNATIONAL SYMPOSIA FOR LIFE SCIENCES AND MEDICINE LA English DT Proceedings Paper CT 14th Keio-University International Symposium for Life Sciences and Medicine CY DEC 11-13, 2003 CL Keio Univ, Tokyo, JAPAN SP Keio Univ Med Sci Fund HO Keio Univ DE pO(2); pH; vascular endothelial growth factor; tumor; nitric oxide ID PROGENITOR CELLS; IN-VIVO; PERMEABILITY; MICROSCOPY; EXPRESSION; SYNTHASE; HYPOXIA; VEGF AB Hypoxia and acidosis are hallmarks of metabolic environment in solid tumors and regulate expression of vascular endothelial growth factor (VEGF), a key angiogenesis factor. We developed a novel in vivo microscopy technique to simultaneously measure VEGF promoter activity, pO(2) and pH. To monitor VEGF expression in vivo, we engineered human glioma cells that express green fluorescent protein (GFP) under the control of VEGF promoter. Tissue pO(2) and pH were determined by phosphorescence quenching microscopy and ratio imaging microscopy, respectively These techniques have allowed us to show that VEGF transcription in brain tumors is regulated by tissue pO(2) and pH via distinct pathways. Nitric oxide (NO) is a multi functional gaseous molecule and regulates various physiological functions. We have shown that NO mediates vessel tone, blood flow, vascular permeability and leukocyte-endothelial interactions in solid tumors. Furthermore, we found that endothelial NO synthase (eNOS) plays predominant role in VEGF-induced angiogenesis and vascular permeability using angiogenic gel model in NOS deficient mice. These findings and the resulting mechanistic insights in the regulation of angiogenesis by gaseous molecules have significant implications for novel tumor detection and treatment strategies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Edwin L Steele Lab, 100 Blossom St,COX 7, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 37-3, HONGO 3-CHOME BONKYO-KU, TOKYO, 113, JAPAN BN 4-431-22135-2 J9 KEIO U INT SYMP LIFE JI Keio Univ. Int. Symp. Life Sci. Med PY 2005 VL 13 BP 283 EP 290 PG 8 WC Engineering, Biomedical; Gastroenterology & Hepatology; Peripheral Vascular Disease SC Engineering; Gastroenterology & Hepatology; Cardiovascular System & Cardiology GA BBN74 UT WOS:000226302200041 ER PT J AU Nadol, JB Pilch, BZ AF Nadol, JB Pilch, BZ TI Untitled SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY AND ITS RELATED SPECIALTIES LA English DT Editorial Material ID METASTASIZING PLEOMORPHIC ADENOMA C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jnadol@meei.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Relat. Spec. PY 2005 VL 67 IS 6 BP 361 EP 362 DI 10.1159/000090048 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA 993LJ UT WOS:000233955300009 ER PT J AU Rossi, MJ Sundararaj, K Koybasi, S Phillips, MS Szulc, ZM Bielawska, A Day, TA Obeid, LM Hannun, YA Ogretmen, B AF Rossi, MJ Sundararaj, K Koybasi, S Phillips, MS Szulc, ZM Bielawska, A Day, TA Obeid, LM Hannun, YA Ogretmen, B TI Inhibition of growth and telomerase activity by novel cationic ceramide analogs with high solubility in human head and neck squamous cell carcinoma cells SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 21-24, 2003 CL ORLANDO, FL SP Amer Acad Otolaryngol Head & Neck Surg ID CANCER; LINE; CHEMOTHERAPY; GEMCITABINE; MECHANISMS; CISPLATIN AB OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is notoriously resistant to chemotherapy. The sphingolipid ceramide and its analogs have been demonstrated to exert antitumor activity in many cell types; however, the effectiveness of these analogs has been limited by potency and solubility. This study focuses on the effects of novel highly soluble cationic pyridinium-ceramides, alone and in combination with various chemotherapeutic agents, on cell survival, telomerase activity, and cell cycle arrest in HNSCC cell lines in vitro. METHODS: The concentration of pyridinium-ceramides and chemotherapeutic agents that inhibited cell growth by 50% (IC50) was determined by MTT cell survival assays. The cell cycle profiles were determined by flow cytometry. Telomerase activity was determined by telomerase repeat amplification protocol (TRAP) assay. RESULTS: Treatment of the human UM-SCC-22A (SCC of the hypopharynx) cells, as well as various other HNSCC cell lines, with C-6-Pyr-Cer resulted in the inhibition of cell survival with an IC50 concentration of approximately 250 to 300 nM at 96 hours, whereas its IC50 was greater than 1000 nM in non-cancerous Wi-38 human lung fibroblasts, and adult human epidermal keratinocytes. Moreover, treatment with C-6-Pyr-Cer also resulted in cell cycle arrest in G0/G1, which correlated with a significant inhibition of telomerase activity in UM-SCC-22A cells. Additional results demonstrated that the combination of C-6-Pyr-Cer with gemcitabine (GMZ) or doxorubicin (DOX), which have the lowest IC50 concentrations among various chemotherapeutic drugs in these cells, enhances the effects of these drugs in the inhibition of telomerase and cell growth. CONCLUSIONS: These data suggest that the novel C-6-Pyr-Cer with high solubility and bioavailability may lead to the development of new therapeutic strategies that target telomerase for the treatment of HNSCC. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. Med Univ S Carolina, Div Head & Neck Oncol Surg, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Ogretmen, B (reprint author), 173 Ashley Ave,BSB 518E, Charleston, SC 29425 USA. EM ogretmen@musc.edu OI Szulc, Zdzislaw M./0000-0003-1756-9028; obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132, R01 CA88932]; NIA NIH HHS [AG16583] NR 21 TC 30 Z9 32 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2005 VL 132 IS 1 BP 55 EP 62 DI 10.1016/j.otohns.2004.08.015 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 886HA UT WOS:000226216300010 PM 15632910 ER PT J AU Merchant, SN Adams, JC Nadol, JB AF Merchant, SN Adams, JC Nadol, JB TI Pathophysiology of Meniere's syndrome: Are symptoms caused by endolymphatic hydrops? SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 02-03, 2004 CL Phoenix, AZ SP Amer Soc Pediat Otolaryngol DE endolymphatic hydrops; Meniere's syndrome; temporal bone ID FINE-STRUCTURE; TEMPORAL BONE; MOUSE MODEL; GUINEA-PIG; IN-VIVO; DISEASE; COCHLEA; CELLS; DEAFNESS AB Background: The association of Menire's syndrome with endolymphatic hydrops has led to the formation of a central hypothesis: many possible etiologic factors lead to hydrops, and hydrops in turn generates the symptoms. However, this hypothesis of hydrops as being the final common pathway has not been proven conclusively. Specific Aim: To examine human temporal bones with respect to the role of hydrops in causing symptoms in Meniere's syndrome. If the central hypothesis were true, every case of Menire's syndrome should have hydrops and every case of hydrops should show the typical symptoms. Methods: Review of archival temporal bone cases with a clinical diagnosis of Meniere's syndrome (28 cases) or a histopathologic diagnosis of hydrops (79 cases). Results: All 28 cases with classical symptoms of Meniere's syndrome showed hydrops in at least one ear. However, the reverse was not true. There were 9 cases with idiopathic hydrops and 10 cases with secondary hydrops, but the patients did not exhibit the classic symptoms of Meniere's syndrome. A review of the literature revealed cases with asymptomatic hydrops (similar to the current study), as well as cases where symptoms of Meniere's syndrome existed during life but no hydrops was observed on histology. We also review recent experimental data where obstruction of the endolymphatic duct in guinea pigs resulted in cytochemical abnormalities within fibrocytes of the spiral ligament before development of hydrops. This result is consistent with the hypothesis that hydrops resulted from disordered fluid homeostasis caused by disruption of regulatory elements within the spiral ligament. Conclusion: Endolymphatic hydrops should be considered as a histologic marker for Meniere's syndrome rather than being directly responsible for its symptoms. C1 Harvard Univ, Dept Otolaryngol, Otopathol Lab,Sch Med, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, Boston, MA 02114 USA. RP Merchant, SN (reprint author), Harvard Univ, Dept Otolaryngol, Otopathol Lab,Sch Med, Massachusetts Eye & Ear Infirm,Dept Otol & Laryng, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu NR 49 TC 178 Z9 190 U1 3 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JAN PY 2005 VL 26 IS 1 BP 74 EP 81 DI 10.1097/00129492-200501000-00013 PG 8 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 957ZH UT WOS:000231411600012 PM 15699723 ER PT J AU Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J AF Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J TI Core outcome measures for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID QUALITY-OF-LIFE; LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CONSORT STATEMENT; HEALTH-STATUS; POSTHERPETIC NEURALGIA; NEUROPATHIC PAIN; INSTRUMENTS; SCORES C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Harvard Univ, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Univ Munich, D-80539 Munich, Germany. AstraZeneca, Wilmington, DE USA. Univ Queensland, Brisbane, Qld, Australia. Tufts Univ, Boston, MA 02111 USA. Merck & Co Inc, Blue Bell, PA USA. Amer Chron Pain Assoc, Rocklin, CA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. US FDA, Rockville, MD 20857 USA. Univ Toronto, Hlth Network, Toronto, ON, Canada. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut, E Hanover, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. NINDS, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14627 USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. NeurogesX, San Carlos, CA USA. Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, San Diego, CA 92103 USA. US Dept Vet Affairs, Washington, DC USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 85 TC 1117 Z9 1134 U1 15 U2 80 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2005 VL 113 IS 1-2 BP 9 EP 19 DI 10.1016/j.pain.2004.09.012 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891PG UT WOS:000226592400005 PM 15621359 ER PT J AU Dey, DD Landrum, O Oaklander, AL AF Dey, DD Landrum, O Oaklander, AL TI Central neuropathic itch from spinal-cord cavernous hemangioma: a human case, a possible animal model, and hypotheses about pathogenesis SO PAIN LA English DT Article DE pruritus; autotomy; pain; spinal cord injury; animal model; excessive grooming ID UNILATERAL PRURITUS; PAIN BEHAVIOR; INJURY; INTERLEUKIN-10; BRAIN; SKIN; RAT AB Cavernous hemangionias (cavernomas) of the spinal cord are rare congenital malformations that comprise less than 5% of all intramedullary lesions. Despite this rarity, we describe the third case of central neuropathic itch associated with intramedullary cavernoma. Since fewer than 10 cases of central spinal itch from all causes have been published, this concurrence suggests the possibility of a specific association. A middle-aged man developed chronic disabling neuropathic itch and pain affecting his left shoulder and arm after frank hemorrhage of a midcervical cavernoma. We hypothesize that the relatively rostro-dorsal location of his lesion increased its likelihood of causing itch as well as pain. The microscopic pathology of cavernomas, specifically their gliotic rim containing hemosiderin-laden phagocytes. fosters ectopic firing of nearby neurons and makes cranial cavernomas highly epileptogenic. We hypothesize that these pathological features predispose cavernomas to cause central itch if they are located near, but spare, the central itch projection neurons in lamina I of the dorsal horn. Quisqualate injections into the deeper layers (neck) of the dorsal horns of rats produce pathologically similar lesions. Such rats develop unilateral dermatomal hyperalgesia and self-injurious Scratching and biting (autotomy). Although this pathological grooming is currently interpreted as a response to chronic pain, we propose that it more likely models scratching provoked by central neuropathic itch. as seen in our patient and others. Study of quisqualate-injected rats may provide leads towards new treatments for neuropathic itch. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM aoaklander@partners.org NR 28 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2005 VL 113 IS 1-2 BP 233 EP 237 DI 10.1016/j.pain.2004.09.032 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891PG UT WOS:000226592400030 PM 15621384 ER PT J AU Alsfasser, G Antoniu, B Thayer, SP Warshaw, AL Fernandez-del Castillo, C AF Alsfasser, G Antoniu, B Thayer, SP Warshaw, AL Fernandez-del Castillo, C TI Degradation and inactivation of plasma tumor necrosis factor-alpha by pancreatic proteases in experimental acute pancreatitis SO PANCREATOLOGY LA English DT Article DE acute pancreatitis; tumor necrosis factor-alpha; cytokine; trypsin digestion; cytokine; pancreatic proteases, bioassay ID POST-ERP PANCREATITIS; NECROTIZING PANCREATITIS; INFLAMMATORY MEDIATORS; ORGAN FAILURE; SERUM; THERAPY; TNF; INTERLEUKIN-10; CYTOKINES; SEVERITY AB Background: Release of TNF alpha is thought to play an important role in mediating systemic effects in acute pancreatitis (AP). We have been unable to find an elevation of plasma TNF alpha in AP and hypothesize that it is susceptible to catabolism by circulating pancreatic proteases. Methods: ( 1) AP was induced in Sprague-Dawley rats by cerulein hyperstimulation preceded by intraductal infusion of saline ( mild) or glycodeoxycholic acid ( severe). Healthy and sham-operated animals served as controls. Severity of pancreatitis was confirmed by histology. Plasma TNF alpha levels were measured at various time points after induction of AP with competitive ELISA. ( 2) Recombinant rat TNF alpha (rrTNF alpha) was incubated with trypsin, elastase, chymotrypsin and pepsin. Western Blot was performed to visualize TNF degradation. ( 3) RrTNF alpha was incubated in a concentration and time-dependant manner with proteases and TNF bioactivity was evaluated with a cytotoxicity assay. Results: ( 1) Plasma TNF alpha levels in severe pancreatitis were significantly lower than in sham-operated controls after 0.5 and 6 h. ( 2) Incubation with proteases showed degradation in the presence of trypsin, elastase and chymotrypsin and no effect of pepsin. ( 3) There was a concentration dependent inactivation of rrTNF alpha in the presence of pancreatic proteases and a complete time-dependent inactivation in the presence of trypsin. Conclusion: Plasma TNF alpha does not rise in experimental AP, and levels are significantly lower in severe pancreatitis compared to sham-operated controls. Our study demonstrates degradation and inactivation of TNF alpha by pancreatic proteases, suggesting that it is unlikely it plays an important role in the development of distant organ failure. Copyright (C) 2005 S. Karger AG, Basel and IAP. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, WACC 336,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org FU NIDDK NIH HHS [K08 DK071329] NR 41 TC 9 Z9 12 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2005 VL 5 IS 1 BP 37 EP 43 DI 10.1159/000084489 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 920DC UT WOS:000228668500007 PM 15775698 ER PT J AU Tseng, JF Willett, CG Fernandez-del Castillo, C Ryan, DP Clark, JW Zhu, AX Rattner, DW Winkelmann, JL Warshaw, AL AF Tseng, JF Willett, CG Fernandez-del Castillo, C Ryan, DP Clark, JW Zhu, AX Rattner, DW Winkelmann, JL Warshaw, AL TI Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations SO PANCREATOLOGY LA English DT Article DE pancreatic adenocarcinoma; immunity; vaccines; immunotherapy; clinical trial ID DELAYED-TYPE HYPERSENSITIVITY; LUNG-CANCER PATIENTS; CLINICAL-TRIAL; GENE-TRANSFER; SOLID TUMORS; ANTIGENS; IMMUNOTHERAPY; IMMUNIZATION; CARCINOMA; VACCINES AB Background: Immunotherapy has been proposed as a novel treatment for pancreatic cancer. However, patients with pancreatic cancer have been observed to have depressed immune responses, suggesting that immunotherapy might have limited utility in this group of patients. We sought to determine whether patients undergoing postresection or primary medical treatment for pancreatic adenocarcinoma were immunocompetent. Methods: We enrolled patients with pancreatic adenocarcinoma scheduled for postresection or primary chemotherapy and/or radiation therapy. At the initiation of therapy, the patients had an anergy panel placed and baseline blood work performed. During the first week of treatment, patients received tetanus toxoid ( TT), Haemophilus influenzae and Pneumococcus vaccines. Twelve weeks after vaccine administration, IgG titers against the 3 administered vaccines were done, and lymphocyte proliferation assays in response to TT were performed. Results: Eighteen patients were originally enrolled, and 14 patients completed all elements of the trial. Anergy panel responses were obtained for 15 patients who comprised the final study group; both pre- and postvaccination data were available for 14 patients. Nine of 15 patients demonstrated at least a 10-mm induration in response to mumps or Candida antigen (60% response rate, 95% confidence interval (CI) 32 - 84%). Thirteen of 14 patients demonstrated a >= 3- fold increase in IgG against one or more vaccines (93% response rate, 95% CI 66 - 100%). Nine of 14 patients (64% response rate, 95% CI 35 - 87%) demonstrated at least a 3-fold rise of lymphocyte proliferation against TT. Conclusions: Patients with pancreatic cancer were capable of mounting effective cellular and humoral responses to standard vaccines. These data suggest that immunotherapy for pancreatic cancer may be feasible and merits further investigation. Copyright (C) 2005 S. Karger AG, Basel and IAP. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, White 505, Boston, MA 02114 USA. EM awarshaw@partners.org FU NCI NIH HHS [1 F32 CA 86420] NR 42 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2005 VL 5 IS 1 BP 67 EP 74 DI 10.1159/000084492 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 920DC UT WOS:000228668500012 PM 15775701 ER PT J AU Keck, T Friebe, V Warshaw, AL Antoniu, BA Waneck, G Benz, S Hoptb, UT Fernandez-del-Castillo, C AF Keck, T Friebe, V Warshaw, AL Antoniu, BA Waneck, G Benz, S Hoptb, UT Fernandez-del-Castillo, C TI Pancreatic proteases in serum induce leukocyte-endothelial adhesion and pancreatic microcirculatory failure SO PANCREATOLOGY LA English DT Article DE acute pancreatitis; adhesion molecules; microcirculation; protease inhibition; in vivo confocal microscopy ID ACUTE NECROTIZING PANCREATITIS; INTRAVITAL FLUORESCENCE MICROSCOPY; SCANNING LASER MICROSCOPY; ACUTE LUNG INJURY; ISCHEMIA-REPERFUSION; TRYPSINOGEN ACTIVATION; L-SELECTIN; GABEXATE MESILATE; CELL-INTERACTIONS; UP-REGULATION AB Background: Neutrophil-mediated tissue injury in acute pancreatitis includes a severe reduction of the functional microcirculation via interaction of adhesion molecules on leukocytes (MAC-1) and endothelium (ICAM-1). The hypothesis of the study was that trypsin and elastase in serum alone lead to the expression of these complementary adhesion molecules and result in increased leukocyte-endothelial interaction (LEI). In addition we evaluated the preventative benefit of protease inhibition on these mechanisms. Materials and Methods: In vitro: Cultured endothelial cells (HUVEC) and human leukocytes (PMN) were stimulated with increasing doses of trypsin and elastase. In addition, pre-treatment of PMN or HUVEC was performed with protease inhibitors (Nafamostat mesilate, FUT and gabexate mesilate, FOY). The expression of ICAM-1 or MAC-1 was evaluated by flow cytometry. In vivo: Severe pancreatitis was induced in rats. Microcirculatory disturbances were evaluated by real-time confocal microscopy at 9 h in controls and acute pancreatitis with or without anti-protease treatment. Additionally, the effect of continuous trypsin and elastase infusion on pancreatic microcirculation and LEI were evaluated by intravital fluorescence videomicroscopy. Results: Up-regulation of MAC-1 and ICAM-1 expression requires the presence of serum. The maximal increase of MAC-1 and ICAM-1 expression was found at concentrations of trypsin or elastase characteristic for acute pancreatitis. FUT or FOY significantly reduced protease-induced expression of MAC-1 and ICAM-1. Realtime in-vivo microscopy revealed that functional capillary density in acute pancreatitis was significantly reduced (267.1&PLUSMN; 2.95/mm(2) vs. 91.29&PLUSMN; 12.81/mm(2)) and treatment with FUT significantly reduced this effect (134.6&PLUSMN; 4.6/mm(2); p<0.05 vs. untreated pancreatitis). Infusion of trypsin or elastase alone increased LEI in vivo and reduced pancreatic perfusion. Conclusion: Both trypsin and elastase up-regulate the expression of adhesion molecules on leukocytes and endothelial cells in the presence of serum. Increased LEI and reduced perfusion of the pancreas, characteristic of acute pancreatitis, is induced in vivo by infusion of pancreatic proteases and this effect is partially abrogated by their inhibitors. These results support the role of circulating trypsin and elastase in promoting pancreatic microcirculatory failure in experimental acute pancreatitis. Copyright (C) 2005 S. Karger AG, Basel and IAP. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Freiburg, Dept Surg, Freiburg, Germany. RP Fernandez-del-Castillo, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, WACC 336,15 Parkman St, Boston, MA 02114 USA. EM cfernandez@partners.org NR 72 TC 29 Z9 31 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-3903 J9 PANCREATOLOGY JI Pancreatology PY 2005 VL 5 IS 2-3 BP 241 EP 250 DI 10.1159/000085278 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925EP UT WOS:000229034600019 PM 15855822 ER PT J AU Wegelin, J McNamara, P Durso, R Brown, A McLaren, D AF Wegelin, J McNamara, P Durso, R Brown, A McLaren, D TI Correlates of excessive daytime sleepiness in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE excessive daytime sleepiness; Parkinson's disease; neuropsychology; mood; executive functions; dopamine agonists ID ANXIETY STRESS SCALES; REM-SLEEP; BEHAVIOR DISORDER; DOPAMINE; ASSOCIATION; AMYGDALA; HALLUCINATIONS; DISTURBANCES; EPIDEMIOLOGY; INNERVATION AB Measures of excessive daytime sleepiness, neuropsychologic function, and mood were assessed in twenty-two persons with mid-stage Parkinson's disease (PD) and sixteen age-matched healthy controls. Levodopa dose equivalents (LDE) were computed for the patients. While Epworth sleepiness score (ESS), Mini Mental State Exam, logical memory, Stroop, and the mood scales, reliably distinguished patients from controls, only the mood scales (especially anxiety) were reliably associated with ESS. LDE was not significantly associated with ESS. Excessive daytime sleepiness in patients with mid-stage PD may be more strongly related to anxiety than to other neuropsychologic dysfunction or dopaminergic dosing levels. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Biostat, Sacramento, CA 95817 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Wegelin, J (reprint author), Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Div Biostat, 2921 Stocken Blvd, Sacramento, CA 95817 USA. EM jawegelin@ucdavis.edu NR 54 TC 16 Z9 16 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PY 2005 VL 11 IS 7 BP 441 EP 448 DI 10.1016/j.parkredlis.2005.05.007 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 985PK UT WOS:000233390100006 PM 16154796 ER PT J AU Harmon, W Meyers, K McDonald, R Ingelfinger, J McIntosh, M Tinckam, K Najafian, N Sayegh, M AF Harmon, W Meyers, K McDonald, R Ingelfinger, J McIntosh, M Tinckam, K Najafian, N Sayegh, M TI Calcineurin inhibitor (CNI) avoidance in pediatric renal transplantation (RTx). SO PEDIATRIC TRANSPLANTATION LA English DT Meeting Abstract C1 Childrens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. EMMES Corp, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PY 2005 VL 9 SU 6 MA 41 BP 57 EP 57 PG 1 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 957SB UT WOS:000231392500042 ER PT J AU Bar, M AF Bar, M TI The contribution of top-down predictions to visual recognition SO PERCEPTION LA English DT Meeting Abstract C1 Harvard Univ, Martinos Ctr Biomed Imaging, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02129 USA. EM bar@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2005 VL 34 SU S BP 47 EP 48 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 976IE UT WOS:000232726000113 ER PT J AU de Gelder, BLMF AF de Gelder, BLMF TI Beyond the face: Exploring rapid influences of context on face processing SO PERCEPTION LA English DT Meeting Abstract C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA 02115 USA. EM degelder@nmr.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2005 VL 34 SU S BP 48 EP 48 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 976IE UT WOS:000232726000114 ER PT J AU Tamietto, M Geminiani, G de Gelder, BLMF AF Tamietto, M Geminiani, G de Gelder, BLMF TI Inter-hemispheric interaction for bodily emotional expressions: Is the right-hemisphere superiority related to facial rather than emotional processing? SO PERCEPTION LA English DT Meeting Abstract C1 Univ Turin, Dept Psychol, I-10123 Turin, Italy. Univ Turin, Ctr Cognit Sci, I-10123 Turin, Italy. Tilburg Univ, Cognit Affect Neurosci Lab, Tilburg, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM tamietto@psych.unito.it NR 0 TC 1 Z9 1 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 J9 PERCEPTION JI Perception PY 2005 VL 34 SU S BP 205 EP 206 PG 2 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA 976IE UT WOS:000232726000510 ER PT J AU Tsuang, MT Stone, WS AF Tsuang, Ming T. Stone, William S. BE Maj, M Akiskal, HS Mezzich, JE Okasha, A TI The Future of Cluster A Personality Disorders SO PERSONALITY DISORDERS SE WPA Series in Evidence and Experience in Psychiatry LA English DT Editorial Material; Book Chapter ID SCHIZOPHRENIA; SCHIZOTAXIA; PREVENTION; SEARCH C1 [Tsuang, Ming T.; Stone, William S.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. [Tsuang, Ming T.; Stone, William S.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-09038-1 J9 WPA SER EVID EXPER P PY 2005 VL 8 BP 94 EP 97 D2 10.1002/0470090383 PG 4 WC Psychiatry SC Psychiatry GA BYE02 UT WOS:000298178100008 ER PT J AU Blais, MA AF Blais, Mark A. BE Maj, M Akiskal, HS Mezzich, JE Okasha, A TI Of Narcissism, Narcissistic Personality Disorder and Normal Personality SO PERSONALITY DISORDERS SE WPA Series in Evidence and Experience in Psychiatry LA English DT Editorial Material; Book Chapter ID BORDERLINE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-09038-1 J9 WPA SER EVID EXPER P PY 2005 VL 8 BP 341 EP 343 D2 10.1002/0470090383 PG 3 WC Psychiatry SC Psychiatry GA BYE02 UT WOS:000298178100055 ER PT J AU Spottke, AE Reuter, M Machat, O Bornschein, B von Campenhausen, S Berger, K Koehne-Volland, R Rieke, J Simonow, A Brandstaedter, D Siebert, U Oertel, WH Ulm, G Dodel, R AF Spottke, AE Reuter, M Machat, O Bornschein, B von Campenhausen, S Berger, K Koehne-Volland, R Rieke, J Simonow, A Brandstaedter, D Siebert, U Oertel, WH Ulm, G Dodel, R TI Cost of illness and its predictors for Parkinson's disease in Germany SO PHARMACOECONOMICS LA English DT Article ID QUALITY-OF-LIFE; ECONOMIC-IMPACT; MOTOR FLUCTUATIONS; DEPRESSION; BURDEN; CARE; DYSKINESIAS; FREQUENCY; MORTALITY; SEVERITY AB Objective: To prospectively evaluate the health economic burden of patients with Parkinson's disease (PD) in Germany over a 6-month observation period and to identify the predictors of these costs. Study design and methods: Direct and indirect costs were evaluated in 145 patients with PD (mean age 67.3 +/- 9.6 years). PD, patients were recruited from an outpatient department for movement disorders, a specialised PD clinic, two office-based neurologists and general practitioners, all located in Germany, and were enrolled between January and June 2000. Relevant economic data were documented in a patient diary over the 6-month period. Clinical evaluations (Unified Parkinson's Disease Rating Scale [UPDRS]) were performed at baseline and at 3 and 6 months. Costs were derived from various German medical economic resources. Costs were calculated from the perspective of healthcare and transfer payment providers and the individual patient. Indirect costs for lost productivity were also calculated. Costs are presented as means standard deviation (SD). Multivariate regression analyses were performed to identify independent cost predictors. Costs are in year 2000-02 values. Results: We estimated average per patient direct, indirect and total costs for the 6-month observation period. The costs from the perspective of statutory health insurance (Gesetzliche Krankenkversicherung [GKV]) consisted of direct medical costs EURO1370 +/- EURO3240, including rehabilitation (EURO420 +/- EURO1630), hospitalisation (EURO710 +/- EURO2520), outpatient treatment (EURO40 +/- EURO30), ancillary treatment (EURO190 +/- EURO280) and ambulatory diagnostic procedures (EURO10 +/- EURO30). In addition, parkinsonian drug costs were EURO1520 +/- EURO1250. Non-medical direct costs calculated from the GKV perspective were estimated to be EURO480 +/- EURO1710, which included transportation (EURO10 +/- EURO20), special equipment (EURO420 +/- EURO1640), social/ home-help services (EURO10 +/- EURO110) and sickness benefit (EURO40 +/- EURO540). The total medical (including drug costs) and non-medical direct costs for the GKV were EURO3380 +/- EURO4230. Univariate predictors for GKV direct costs included occurrence of motor complications and falls, disease severity, nightmares and dementia. However, multivariate analyses only suggested disease severity and health-related quality of life as significant predictors. For nursing insurance, payments of El 330 +/- EURO2890 were calculated. For retirement insurance, payments were EURO650 +/- EURO1510 and there were patient (or caregiver) costs of EURO1490 +/- EURO2730. Total indirect costs amounted to EURO3180 +/- EURO6480. Conclusion: According to our study, PD puts a high financial burden on society and underscores the need for further economic and medical research to optimise treatment for PD. C1 Univ Bonn, Dept Neurol, D-53127 Bonn, Germany. Univ Marburg, Dept Neurol, Marburg, Germany. Metronomia, Munich, Germany. MERG, Munich, Germany. Paracelsus Elena Clin, Kassel, Germany. Harvard Univ, Sch Med, Inst Technol Assessment, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Dodel, R (reprint author), Univ Bonn, Dept Neurol, Siegmund Freud Str 25, D-53127 Bonn, Germany. EM richard.dodel@ukb.uni-bonn.de NR 45 TC 75 Z9 76 U1 1 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PY 2005 VL 23 IS 8 BP 817 EP 836 DI 10.2165/00019053-200523080-00007 PG 20 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 959DE UT WOS:000231496300007 PM 16097843 ER PT S AU Chatterjee, B Echchgadda, I Song, CS AF Chatterjee, B Echchgadda, I Song, CS BE Sies, H Packer, L TI Vitamin D receptor regulation of the steroid/bile acid sulfotransferase SULT2A1 SO PHASE II CONJUGATION ENZYMES AND TRANSPORT SYSTEMS SE Methods in Enzymology LA English DT Review; Book Chapter ID HUMAN HYDROXYSTEROID SULFOTRANSFERASE; HUMAN DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; HUMAN CYTOSOLIC SULFOTRANSFERASES; FARNESOID X-RECEPTOR; MOLECULAR-CLONING; LITHOCHOLIC ACID; RAT-LIVER; BILE-ACID; TRANSCRIPTIONAL CONTROL; CRYSTAL-STRUCTURE AB SULT2A1 is a sulfo-conjugating phase 11 enzyme expressed at very high levels in the liver and intestine, the two major first-pass metabolic tissues, and in the steroidogenic adrenal tissue. SULT2A1 acts preferentially on the hydroxysteroids dehydroepiandrosterone, testosterone/ dihydrotestosterone, and pregnenolone and on cholesterol-derived amphipathic sterol bile acids. Several therapeutic drugs and other xenobiotics, which include xenoestrogens, are also sulfonated by this cytosolic steroid/ bile acid sulfotransferase. Nonsteroid nuclear receptors with key roles in the metabolism and detoxification of endobiotics and xenobiotics, such as bile acid-activated farnesoid X receptor, xenobiotic-activated pregnane X receptor and constitutive androstane receptor, and lipid-activated peroxisome proliferator-activated receptor-a, mediate transcription induction of SULT2A1 in the enterohepatic system. The ligand-activated vitamin D receptor (VDR) is another nuclear receptor that stimulates SULT2A1 transcription, and the regulatory elements in human, mouse, and rat promoters directing this induction have been characterized. Given that bile acid sulfonation is catalyzed exclusively by SULT2A1 and that the 3 alpha-sulfate of the highly toxic lithocholic acid is a major excretory metabolite in humans, we speculate that a role for the VDR pathway in SULT2A1 expression may have emerged to shield first-pass tissues from the cytotoxic effects of a bile acid overload arising from disrupted sterol homeostasis triggered by endogenous and exogenous factors. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78285 USA. FU NIA NIH HHS [R01-AG-10486, R01-AG-19660] NR 55 TC 36 Z9 36 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182805-0 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 400 BP 165 EP 191 DI 10.1016/S0076-6879(05)00010-8 PG 27 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDO60 UT WOS:000234565000010 PM 16399349 ER PT J AU Lambrechts, SAG Demidova, TN Aalders, MCG Hasan, T Hamblin, MR AF Lambrechts, SAG Demidova, TN Aalders, MCG Hasan, T Hamblin, MR TI Photodynamic therapy for Staphylococcus aureus infected burn wounds in mice SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID MESOSUBSTITUTED CATIONIC PORPHYRINS; PROTOPORPHYRIN-IX ACCUMULATION; IN-VIVO; 5-AMINOLEVULINIC ACID; BIOFILM INFECTION; ESCHERICHIA-COLI; ANIMAL-MODEL; SKIN; BACTERIA; PHOTOSENSITIZATION AB The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin(PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 mu M PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Univ Amsterdam, Acad Med Ctr, Ctr Laser, NL-1105 AZ Amsterdam, Netherlands. Tufts Univ, Dept Cell Mol & Dev Biol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. 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 Aalders, Maurice/H-8474-2014; OI Lambrechts, Saskia/0000-0003-3400-4520; Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01-AI050875] NR 47 TC 94 Z9 97 U1 1 U2 17 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2005 VL 4 IS 7 BP 503 EP 509 DI 10.1039/b502125a PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 940BB UT WOS:000230117600002 PM 15986057 ER PT S AU Pierce, MC Klein, A Burns, JA Shishkov, M Park, BH Tearney, GJ Bouma, BE Zeitels, SM de Boer, JF AF Pierce, MC Klein, A Burns, JA Shishkov, M Park, BH Tearney, GJ Bouma, BE Zeitels, SM de Boer, JF BE Bartels, KE Bass, LA DeRiese, WTW Gregory, KW Hirschberg, H Katzir, A Kollias, N Madsen, SJ Malek, RS McNallyHeintzelman, KM Tate, LP Trowers, EA Wong, BJF TI Endoscopic imaging of the human vocal cords using polarization-sensitive optical coherence tomography SO Photonic Therapeutics and Diagnostics SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Photonic Therapeutics and Diagnostics CY JAN 22-25, 2005 CL San Jose, CA SP SPIE DE otolaryngology; optical imaging; birefringence; cartilage; fiber-optic probes ID BIREFRINGENCE AB Endoscopic polarization-sensitive optical coherence tomography (PS-OCT) was used to obtain cross-sectional images of laryngeal tissues in human subjects, in vivo. Imaging in tissue to a depth of 1.2 mm and with axial resolution below 10 mu m enabled the epithelial layer to be readily identified in OCT intensity images, with the underlying superficial lamina propria characterized by an increased backscatter signal, and increased birefringence in polarization-sensitive images. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Pierce, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, BAR 714,50 Blossom St, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5659-4 J9 P SOC PHOTO-OPT INS PY 2005 VL 5686 BP 307 EP 309 DI 10.1117/12.589870 PG 3 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BCI71 UT WOS:000229607700043 ER PT J AU Barbeau, EM Wolin, KY Naumova, EN Balbach, E AF Barbeau, EM Wolin, KY Naumova, EN Balbach, E TI Tobacco advertising in communities: associations with race and class SO PREVENTIVE MEDICINE LA English DT Article DE smoking; social inequalities; tobacco industry; tobacco advertising and promotion ID CIGARETTE-SMOKING; UNITED-STATES; YOUNG-ADULTS; ADOLESCENT SMOKING; SALES PROMOTION; FOLLOW-UP; NHANES-I; EXPOSURE; INDUSTRY; SUSCEPTIBILITY AB Background. Individuals of lower socioeconomic position smoke at higher rates than those of higher socioeconomic position. Because of this disparity, the National Cancer Institute has called for studies of targeted tobacco marketing to clarify mechanisms contributing to higher tobacco use among low-income Americans and other high-risk populations. Methods. We observed tobacco industry marketing in six Boston area communities (two of high socioeconomic position and four of low position; total of 41 observations) and in selected print publications that circulated in those communities during a 22-month period in 2000-2002. Results. On average, there were fewer tobacco advertisements in the higher socioeconomic communities, compared to the lower socioeconomic communities (P < 0.001). In the low socioeconomic communities, there were more than three times as many brand advertisements as youth access signs (P = 0.0012). Although brand advertisements outnumbered smoke-free signs, on average, there was no difference in the ratio of brand advertisements to smoke-free signs in low and high socioeconomic communities (P = 0.06). Conclusions. The tobacco industry is actively present in community settings, particularly in communities with a low socioeconomic profile (SEP). Tobacco control researchers and advocates need to continue to monitor the tobacco industry's behavior at the community level and develop strategies to counter this behavior. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Family Med & Community Hlth, Boston, MA 02111 USA. Tufts Univ, Coll Arts & Sci, Community Hlth Program, Medford, MA 02155 USA. RP Barbeau, EM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St,250 Smith Bldg, Boston, MA 02115 USA. EM Elizabeth_Barbeau@dfci.harvard.edu RI Naumova, Elena/C-5954-2011; Wolin, Kathleen/I-2154-2014; OI Wolin, Kathleen/0000-0001-7950-9042; Naumova, Elena/0000-0002-9562-4734 NR 62 TC 53 Z9 53 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 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2005 VL 40 IS 1 BP 16 EP 22 DI 10.1016/j.ypmed.2004.04.056 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 875XI UT WOS:000225455400003 PM 15530576 ER PT J AU Liu, C Waters, DD AF Liu, C Waters, DD TI Chlamydia pneumoniae and atherosclerosis: from Koch's postulates to clinical trials SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID CORONARY-HEART-DISEASE; HERPES-SIMPLEX-VIRUS; NECROSIS-FACTOR-ALPHA; LONG-TERM PROGNOSIS; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; SECONDARY PREVENTION; CYTOMEGALOVIRUS-INFECTION; RABBIT MODEL; RISK C1 San Francisco Gen Hosp, Div Cardiol, Dept Med, San Francisco, CA 94110 USA. Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Waters, DD (reprint author), San Francisco Gen Hosp, Div Cardiol, Dept Med, Room 5G1,1001 Potrero Ave, San Francisco, CA 94110 USA. EM dwaters@medsfgh.ucsf.edu NR 46 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD JAN-FEB PY 2005 VL 47 IS 4 BP 230 EP 239 DI 10.1016/j.pcad.2005.01.001 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 946PR UT WOS:000230585000003 PM 15991152 ER PT J AU Bober, SL Park, ER Diller, L AF Bober, SL Park, ER Diller, L TI Hodgkin's disease survivorship and breast cancer risk: A qualitative exploration of young womens' perceptions SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S11 EP S12 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400020 ER PT J AU Cooley, ME Farber, D Rimar, J Knafl, G McCorkle, R AF Cooley, ME Farber, D Rimar, J Knafl, G McCorkle, R TI The use of health-related quality of life questionnaires as predictors of unscheduled Healthcare visits in outpatient oncology SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S20 EP S20 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400036 ER PT J AU Kornblith, AB Regan, M Kim, Y Parker, B Bennett, S Winer, E AF Kornblith, AB Regan, M Kim, Y Parker, B Bennett, S Winer, E TI Cancer-related communication between patients and their spouses SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S13 EP S14 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400024 ER PT J AU Lockwood, R Diller, L Recklitis, CJ AF Lockwood, R Diller, L Recklitis, CJ TI Suicidal symptoms among childhood cancer survivors: Prevalence and risk factors SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Suffolk Univ, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S50 EP S51 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400094 ER PT J AU Lucas, MR AF Lucas, MR TI The unique care needs of the primary brain tumor patient population SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S31 EP S31 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400056 ER PT J AU Moore, CW Muriel, AC Pirl, WF Beiser, ME Rauch, PK AF Moore, CW Muriel, AC Pirl, WF Beiser, ME Rauch, PK TI Adult cancer patients as parents: What do oncologists and primary care providers know? SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S58 EP S58 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400108 ER PT J AU Muriel, AC Beale, EA Fasciano, KM Kissane, DW Lederberg, MS AF Muriel, AC Beale, EA Fasciano, KM Kissane, DW Lederberg, MS TI Family cCentered care in psychosocial oncology: Supporting the children of adults with cancer SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S2 EP S3 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400005 ER PT J AU Pirl, WF AF Pirl, WF TI Retrospective study of OROS (R) Methylphenidate (Concerta) for cancer-related fatigue SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S61 EP S61 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400114 ER PT J AU Pirl, WF Muriel, AC Beiser, M Moore, CW AF Pirl, WF Muriel, AC Beiser, M Moore, CW TI Differences between primary care and oncology providers in managing depression SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S7 EP S8 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400012 ER PT J AU Rodriguez, P Recklitis, CJ AF Rodriguez, P Recklitis, CJ TI Screening adult survivors of childhood cancer with the BSI-18: a comparison with the SCL-90-R SO PSYCHO-ONCOLOGY LA English DT Meeting Abstract C1 Suffolk Univ, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JAN PY 2005 VL 14 IS 1 SU S BP S50 EP S50 PG 1 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 899YT UT WOS:000227182400093 ER PT J AU Wilkins, JN Majewska, MD Van Gorp, W Li, SH Hinken, C Plotkin, D Setoda, D AF Wilkins, JN Majewska, MD Van Gorp, W Li, SH Hinken, C Plotkin, D Setoda, D TI DHEAS and POMS measures identify cocaine dependence treatment outcome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE cocaine; profile of mood states; dehydroepiandrosterone sulphate; DHEA; DHEAS; dehydroepiandrosterone; cortisol; abstinent; relapsed; dropped out ID CORTICOTROPIN-RELEASING-FACTOR; DEHYDROEPIANDROSTERONE-SULFATE; MAJOR DEPRESSION; ABSTINENCE SYMPTOMATOLOGY; SMOKING-CESSATION; SALIVARY CORTISOL; DRUG-ADDICTION; PLASMA-LEVELS; FOLLOW-UP; ABUSERS AB Early attrition is a significant problem in the treatment of cocaine dependence, but it is unclear why some patients succeed in treatment while others relapse or drop out of treatment without a demonstrated relapse. The goal of this study was to determine whether baseline levels of select hormones, including the adrenal hormone and excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), would distinguish between treatment outcome groups. Based on the literature, completion of 90 days of treatment was established as a key outcome variable. Methods: Quantitative urine levels of the cocaine metabolite benzoylecgonine (BE) and other substance of abuse analytes, plasma levels of DHEAS, DHEA, cortisol., and prolactin, and the profile of mood states (POMS) were serially measured in 38 mate cocaine-dependent (DSM-IV) patients and in 28 controls of similar gender and age over a six month study. Exclusion criteria for the patients and controls included Axis I mood, anxiety or psychotic disorders. The patients could not manifest substance dependence except to cocaine. The patients and controls received remuneration for urine and blood collection. Blood samples for hormone levels were obtained between 8 and 10 a.m. on days 1, 14 and 21 of a 21-day inpatient treatment program and throughout 6 months of outpatient study visits at 45-day intervals. Results: Attrition from treatment and study appointments occurred predominately at the junction between inpatient and outpatient programs. Forty percent of patients made the transition to outpatient treatment and remained abstinent and in treatment for a median of 103 days (ABST). Forty-two percent of patients dropped out of treatment during the inpatient stay or never returned after completing the inpatient program (DO) and 18% had a documented relapse either during, or within the first week after, the inpatient stay (REL). POMS total scores were elevated at treatment entry for both the ABST and DO groups. Plasma DHEAS levels in the DO patients were decreased compared to controls and increased in the ABST patients. POMS total scores for the REL patients at baseline were at control levels. Baseline cortisol levels were not statistically different between the outcome groups, though they were elevated for all cocaine patient groups. When treatment outcome was collapsed into whether patients completed (ABST) or did not complete 90 days of treatment (90N), ABST plasma DHEAS and cortisol. were significantly elevated compared to the 90N patients and controls across the first 3 weeks of cocaine withdrawal. Conclusions: At treatment entry, each of the three patient outcome groups was identified by Levels of circulating DHEAS and distressed mood. In the ABST patients, distressed mood during withdrawal may have been mitigated through antidepressant-like actions of enhanced endogenous DHEAS activity, thus contributing to improved abstinence and treatment retention. Patients, such as the DO group, with high levels of distressed mood at treatment entry and low DHEAS levels may benefit from adjunctive pharmacotherapy that targets DHEAS and POMS measures. Patients, such as the REL group, who tack distressed mood at treatment entry, may require intense application of motivational approaches plus residential treatment. (C) 2004 Elsevier Ltd. All rights reserved. C1 Cedars Sinai Med Ctr, Dept Psychiat, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Natl Inst Drug Abuse, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. RP Wilkins, JN (reprint author), Cedars Sinai Med Ctr, Dept Psychiat, 8730 Alden Dr,Room C-301, Los Angeles, CA 90048 USA. EM wilkinsj@cshs.org NR 69 TC 27 Z9 27 U1 1 U2 5 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 JAN PY 2005 VL 30 IS 1 BP 18 EP 28 DI 10.1016/j.psyneuen.2004.04.006 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 858TL UT WOS:000224214700003 PM 15358439 ER PT J AU Stein, MB Pollack, MH Bystritsky, A Kelsey, JE Mangano, RM AF Stein, MB Pollack, MH Bystritsky, A Kelsey, JE Mangano, RM TI Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial SO PSYCHOPHARMACOLOGY LA English DT Article DE social phobia; anxiety disorder; pharmacotherapy; antidepressant ID NATIONAL COMORBIDITY SURVEY; QUALITY-OF-LIFE; DOUBLE-BLIND; SERTRALINE TREATMENT; NONDEPRESSED OUTPATIENTS; PSYCHOMETRIC PROPERTIES; RATING SCALE; PRIMARY-CARE; PHOBIA; PLACEBO AB Rationale: There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition. Objective: To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release ( ER) with placebo in patients with GSAD. Method: Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose ( 75 mg/day), or venlafaxine ER flexible higher dose ( 150 - 225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item ( score 1 or 2), and the proportion of remitters ( defined as an LSAS score of less than or equal to 30). Results: Improvement on the LSAS was greater with venlafaxine ER ( at 75 mg/day or 150 - 225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER ( at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P< 0.001); corresponding remission rates were 31% and 16% ( P< 0.01). There were no differences in outcome according to venlafaxine ER dosage. Conclusions: Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Georgia Inst Mood & Anxiety Disorders, Atlanta, GA USA. Wyeth Res, USA Neurosci Global Clin Res & Dev, Philadelphia, PA USA. RP Stein, MB (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM mstein@ucsd.edu NR 45 TC 65 Z9 66 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2005 VL 177 IS 3 BP 280 EP 288 DI 10.1007/s00213-004-1957-9 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 881BZ UT WOS:000225839700005 PM 15258718 ER PT J AU Egede, LE AF Egede, LE TI Effect of comorbid chronic diseases on prevalence and odds of depression in adults with diabetes SO PSYCHOSOMATIC MEDICINE LA English DT Article DE diabetes; depression; chronic disease; health survey; health service research; health psychology ID PRIMARY-CARE; MAJOR DEPRESSION; UNITED-STATES; METAANALYSIS; INDIVIDUALS; DISABILITY; MORTALITY; WORK; RISK AB Objective: The objective of this study was to determine the effect of coexisting chronic conditions on prevalence and odds of depression in individuals with diabetes. Methods: Data on 1794 adults with diabetes from the 1999 National Health Interview Survey were analyzed. Six chronic conditions were identified: hypertension, coronary artery disease, chronic arthritis, stroke, chronic obstructive pulmonary disease, and end-stage renal disease. Chronic conditions were counted and categorized into 4 groups: diabetes alone, diabetes + 1 condition, diabetes + 2 conditions, and diabetes + 3 or more conditions. Prevalence of depression was calculated by number of chronic conditions and for each condition. Adjusted odds of depression were calculated by number of chronic conditions and for each chronic condition while simultaneously controlling for covariates and for each chronic condition using multiple logistic regression. STATA was used for statistical analyses. Results: Using diabetes alone as reference, adjusted odds of major depression by number of conditions were: diabetes + 1 (1.31; 95% confidence interval [CI], 0.67-2.55), diabetes + 2 (2.09; 95% CI, 1.06-4.12), and diabetes + 3 or more (4.09; 95% CI, 2.04-8.17). Adjusted odds of major depression for each coexisting chronic conditions were: hypertension (1.22; 95% CI, 0.78-1.90), coronary artery disease (2.00; 95% CI, 1.27-3.14), chronic arthritis (2.02; 95% CI, 1.35-3.02), stroke (2.15; 95% CI, 1.10-4.31), chronic obstructive pulmonary disease (0.96; 95% CI, 0.52-1.81), and end-stage renal disease (1.19; 95% CI, 0.57-2.49). Conclusion: Odds of major depression are significantly increased among adults with diabetes in the presence of two or more coexisting chronic conditions, and coexistence of coronary artery disease, chronic arthritis, and stroke in particular, are associated with increased odds of major depression. C1 Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Care Res, 135 Cannon St,Suite 403,POB 250837, Charleston, SC 29425 USA. EM egedel@musc.edu FU AHRQ HHS [5K08HS11418] NR 26 TC 55 Z9 55 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2005 VL 67 IS 1 BP 46 EP 51 DI 10.1097/01.psy.0000149260.82006.fb PG 6 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 892TU UT WOS:000226673700007 PM 15673623 ER PT J AU Surman, OS Fukunishi, I Allen, T Hertl, M AF Surman, OS Fukunishi, I Allen, T Hertl, M TI Live organ donation: Social context, clinical encounter, and the psychology of communication SO PSYCHOSOMATICS LA English DT Article; Proceedings Paper CT 17th World Congress of Psychosomatic Medicine CY AUG 23-28, 2003 CL Waikoloa, HI ID LIVING KIDNEY DONOR; PSYCHIATRIC ASPECTS; UNITED-STATES; TRANSPLANTATION; AUTONOMY; PATIENT; JAPAN AB Organ transplantation is increasingly available to the thousands of patients who suffer from end-organ failure. There has been an attendant increase in demand for living donor participation. This combined with a bioethical focus on autonomy increases the burden of decision on donor candidates. The authors review the history of living donor participation in organ transplantation and explore the psychological dynamics of the clinical encounter between donor and transplant surgeon. The field of communication psychology lends to the understanding of coercion and to the importance of donors possessing a status of patient-hood in the classical Hippocratic condition. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Liver Transplant Serv, Boston, MA USA. Univ Tokyo, Med Ctr, Tokyo, Japan. Calif State Univ Long Beach, Dept Commun Psychol, Long Beach, CA USA. RP Surman, OS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WANG ACC-812,15 Parkman St, Boston, MA 02114 USA. EM osurman@partners.org NR 29 TC 16 Z9 19 U1 1 U2 11 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2005 VL 46 IS 1 BP 1 EP 6 DI 10.1176/appi.psy.46.1.1 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 885JO UT WOS:000226153100001 PM 15765814 ER PT J AU Chang, G Orav, EJ McNamara, TK Tong, MY Antin, JH AF Chang, G Orav, EJ McNamara, TK Tong, MY Antin, JH TI Psychosocial function after hematopoietic stem cell transplantation SO PSYCHOSOMATICS LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOID-LEUKEMIA; QUALITY-OF-LIFE; LONG-TERM SURVIVORS; CANCER-PATIENTS; 1ST YEAR; SMOKING; RECIPIENTS; MORBIDITY; DISTRESS AB The authors report on a prospective cohort study of patients with chronic myelogenous leukemia undergoing allogeneic hematopoietic stem cell transplantation. The purpose was to evaluate the progression of quality of life and mood, as well as patterns of alcohol consumption, a behavior with potential adverse health consequences. Of the 84 subjects who completed serial measures and other interviews at admission for hematopoietic stem cell transplantation and 6-month follow-up, 75 provided data 12 months later. The main findings of this study were that quality of life improves, measures of depressive symptoms decline, and patients drink less alcohol overall. Time was the most important variable accounting for these changes. C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Partners Canc Inst, Boston, MA USA. RP Chang, G (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. EM gchang@partners.org FU PHS HHS [K24 000289] NR 40 TC 19 Z9 20 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2005 VL 46 IS 1 BP 34 EP 40 DI 10.1176/appi.psy.46.1.34 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 885JO UT WOS:000226153100006 PM 15765819 ER PT J AU Ongur, D Farabaugh, A Iosifescu, DV Perlis, R Fava, M AF Ongur, D Farabaugh, A Iosifescu, DV Perlis, R Fava, M TI Tridimensional Personality Questionnaire factors in major depressive disorder: Relationship to anxiety disorder comorbidity and age of onset SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE personality; Tridimensional Personality Questionnaire; anxiety; depression; harm avoidance; early onset ID MOOD; TEMPERAMENT; PATTERNS; TRAITS; STATES AB Objective: We used the Tridimensional Personality Questionnaire (TPQ) to study the relationship between temperamental traits and comorbid anxiety disorders as well as age of onset of major depressive disorder (MDD) in 263 patients with MDD. Methods: Patients recruited for a large clinical study on MDD underwent a Structured Clinical Interview for DSM-III-R assessment and were administered the self-rated TPQ [mean age = 39.5 +/- 10.5 years, women = 138 (53%), initial 17-item Hamilton Rating Scale for Depression (HAM-D-17) score = 19.6 +/- 3.4]. The TPQ was scored for three previously identified factors-harm avoidance (HA), novelty seeking (NS), and reward dependence (RD). Multiple linear regression methods were used to evaluate the relationship between TPQ factors and each comorbid anxiety disorder as well as between early- vs. late-onset MDD, after controlling for age, gender and initial HAM-D-17 score (when these were related to the dependent variable in simple regressions). Results: Social anxiety disorder in MDD was strongly associated with higher scores on HA and lower scores on NS and RD (t = 5.4, p < 0.0001; t = 2.6, p = 0.009; t = 2.2, p = 0.028, respectively). A diagnosis of generalized anxiety disorder in MDD was significantly related to higher HA scores (t = 2.8, p = 0.006). The presence of comorbid obsessive-compulsive disorder was associated with lower NS scores (t = 2.3, p = 0.023) as was that of comorbid panic disorder (t = 2.0, p = 0.051). Finally, the presence of simple phobias was associated with lower scores on RD (t = 2.4, p = 0.016). HA scores were higher in patients with early onset of MDD (adjusted p = 0.05). Early versus late onset of MDD was not significantly related to NS or RD scores. Limitations: Since our sample consisted of moderately depressed outpatients, our ability to generalize our findings to other populations is limited. Conclusions: Features of temperament are related to patterns of anxiety disorder comorbidity and age of onset among patients with MDD. Higher levels of HA and lower levels of RD and NS were associated with an increased risk of anxiety disorder comorbidity in our sample. HA may also be related to early onset of depression. Copyright (C) 2005 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM mfava@partners.org FU NIMH NIH HHS [R01-MH-48-483-05] NR 26 TC 33 Z9 34 U1 1 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2005 VL 74 IS 3 BP 173 EP 178 DI 10.1159/000084002 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 916JV UT WOS:000228382100006 PM 15832068 ER PT J AU Cassano, P Soares, CN Cusin, C Mascarini, A Cohen, LS Fava, M AF Cassano, P Soares, CN Cusin, C Mascarini, A Cohen, LS Fava, M TI Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE depression; fluoxetine; menopause; well-being ID DOUBLE-BLIND; ESTROGEN REPLACEMENT; GENDER-DIFFERENCES; EFFICACY; TRIAL AB Background: We assessed the impact of menopausal status on treatment response and well-being in a cohort of outpatient women with major depressive disorder (DSM-III-R criteria), who received treatment with fluoxetine (20 mg/ day for 8 weeks). Methods: Menopausal status was defined based on age, presence of menstrual irregularity or amenorrhea and vasomotor symptoms. Remission and response of depression were defined as a 17-item Hamilton Depression Rating Scale (HAM-D-17) score <= 7 and a HAM-D-17 decrease >= 50%, respectively. Well-being was assessed by self- rating with the Symptom Questionnaire. Remitters were followed up for 28 additional weeks. Results: No differences in rates of response and remission as well as in levels of well-being were observed among pre- ( n = 121), peri- ( n = 28) and postmenopausal ( n = 35) women at the endpoint of the acute phase, even after adjustment for baseline depression severity. Residual symptoms, however, were significantly more common in postmenopausal women, except for the continuation phase endpoint. Differences in residual symptoms during the acute phase subsided after adjustment for baseline depression severity. Conclusions: Overall, menopausal status did not significantly affect the response to fluoxetine treatment and the degree of posttreatment well- being among major depressive disorder patients. Copyright (c) 2005 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Univ Milan, Monza, Italy. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM pcassano@partners.org RI Cassano, Paolo/I-6959-2012 NR 15 TC 12 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PY 2005 VL 74 IS 6 BP 362 EP 365 DI 10.1159/000087783 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 975LU UT WOS:000232664800005 PM 16244512 ER PT J AU Faw, L Hogue, A Johnson, S Diamond, GM Liddle, HA AF Faw, L Hogue, A Johnson, S Diamond, GM Liddle, HA TI The Adolescent Therapeutic Alliance Scale (ATAS): Initial psychometrics and prediction of outcome in family-based substance abuse prevention counseling SO PSYCHOTHERAPY RESEARCH LA English DT Article DE therapeutic alliance; adolescent development; substance abuse; family-based therapy; therapeutic processes ID WORKING ALLIANCE; NATIONAL-INSTITUTE; PSYCHOTHERAPY; BEHAVIOR; RISK; RELIABILITY; DEPRESSION AB This study piloted a 14-item, observer-rated therapeutic alliance scale with adolescents enrolled in family-based substance abuse prevention counseling. The Adolescent Therapeutic Alliance Scale (ATAS) was drawn from 2 main sources: ( a) items from the Vanderbilt Therapeutic Alliance Scale - Revised based on developmental considerations and (b) Bordin's ( 1979) theory of the alliance as consisting of bond, tasks, and goals. Independent observers rated the therapist - adolescent alliance for 51 at-risk, African American adolescents ( aged 11 - 14 years). Factor analysis suggested the ATAS measures one construct ( eigenvalue = 8.6, accounting for 61.3% of total scale variance). Item loadings ranged from .40 to .90. Convergent validity with both therapist- and observer-rated engagement was also high. Internal consistency reliability ( alpha =. 90) and intraclass correlation (ICC1,2 =. 74) were acceptable. A trend emerged for ATAS ratings to predict improvement in adolescent investment in school. Recommendations are made for future work in developing and implementing measures of therapeutic alliance for adolescents. C1 Columbia Univ, Natl Ctr Addict & Subst Abuse, New York, NY 10017 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Ctr Treatment Res Adolescent Drug Abuse, Miami, FL USA. RP Hogue, A (reprint author), Columbia Univ, Natl Ctr Addict & Subst Abuse, 633 3rd Ave,19th Floor, New York, NY 10017 USA. EM athogue@aol.com RI DIAMOND, GARY/F-1270-2012 NR 44 TC 18 Z9 18 U1 7 U2 9 PU ROUTLEDGE TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1050-3307 J9 PSYCHOTHER RES JI Psychother. Res. PD JAN PY 2005 VL 15 IS 1-2 BP 141 EP 154 DI 10.1080/10503300512331326994 PG 14 WC Psychology, Clinical SC Psychology GA 920XY UT WOS:000228730000014 ER PT J AU Orfaly, RA Biddinger, PD Burstein, JL Leaning, J AF Orfaly, RA Biddinger, PD Burstein, JL Leaning, J TI Integration of academia and practice in preparedness training: The Harvard school of public health experience SO PUBLIC HEALTH REPORTS LA English DT Article AB Given the need for public health professionals well trained in emergency preparedness and response, students in public health programs require ample practical training to prepare them for careers in public health practice. The Harvard School of Public Health Center for Public Health Preparedness has been instrumental in the creation and implementation of a course entitled, "Bioterrorism: Public Health Preparedness and Response." This course features lectures on specific applications of public health practice in emergency preparedness and response. In addition, it provides students the opportunity to operationalize and apply their knowledge during an interactive tabletop exercise. In light of their university affiliations and expertise in providing preparedness training, other Academic Centers for Public Health Preparedness have the opportunity to be instrumental in providing similar training to graduate students of public health. C1 Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, Boston, MA 02120 USA. Harvard Univ, Sch Publ Hlth, Francois Xavier Bagnoud Ctr Hlth & Human Rights, Boston, MA 02120 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RP Orfaly, RA (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, 1552 Tremont St, Boston, MA 02120 USA. EM rorfaly@hsph.harvard.edu NR 2 TC 10 Z9 10 U1 0 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 2005 VL 120 SU 1 BP 48 EP 51 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 940IH UT WOS:000230136400010 PM 16025706 ER PT J AU Anzueto, A Tashkin, D Menjoge, S Kesten, S AF Anzueto, A Tashkin, D Menjoge, S Kesten, S TI One-year analysis of longitudinal changes in spirometry in patients with COPD receiving tiotropium SO PULMONARY PHARMACOLOGY & THERAPEUTICS LA English DT Article DE chronic obstructive pulmonary disease; tiotropium; spirometry; lung function; FEV1 ID OBSTRUCTIVE PULMONARY-DISEASE; AIR-FLOW LIMITATION; LUNG HEALTH; DECLINE; SMOKERS; MILD AB Background: Airway medications have not been shown to reduce the loss of lung function in patients with COPD. We explored whether tiotropium 18 mug once daily could slow the rate of decline of lung function over a 1-year period. Methods: We performed a post-hoc analysis of data from 921 ambulatory COPD patients participating in two, 1-year, double-blind, tiotropium vs. placebo-controlled trials. Serial spirometry was obtained at baseline (before first dose of study drug), on day 8, at 6 weeks, and at 3, 6, 9 and 12 months after start of the study. Results: Baseline demographics and lung function were comparable. Baseline FEV1 was 1.01 +/- 0.41 (SD) L (39 +/-14% predicted). Mean decline in trough FEV1 (i.e. FEV1 23-24 h after prior use of medication) between days 8 and 344 was 58 ml/year in the placebo group and 12 ml/year in the tiotropium group (p=0.005 vs. placebo); and between days 50 and 344 was 59 ml/year in the placebo group and 19 ml/year in the tiotropium group (p=0.036 vs. placebo). Conclusions: Based on a retrospective analysis of 1-year, placebo-controlled clinical trials, tiotropium was associated with a reduced rate of loss of FEV1. Longer-term trials specifically designed to study this effect are required to confirm this observation.(C) 2004 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Pulm Crit Care, San Antonio, TX 78299 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78299 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Anzueto, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pulm Crit Care, 7400 Merton Minter Blvd,111E, San Antonio, TX 78299 USA. EM anzueto@uthcsa.edu NR 29 TC 76 Z9 82 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1094-5539 J9 PULM PHARMACOL THER JI Pulm. Pharmacol. Ther. PY 2005 VL 18 IS 2 BP 75 EP 81 DI 10.1016/j.pupt.2004.10.003 PG 7 WC Pharmacology & Pharmacy; Respiratory System SC Pharmacology & Pharmacy; Respiratory System GA 893CR UT WOS:000226697400001 PM 15649848 ER PT J AU Fischman, AJ AF Fischman, AJ TI Role of [F-18]-dopa-PET imaging in assessing movement disorders SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; PROGRESSIVE SUPRANUCLEAR PALSY; F-18 DOPA-PET; IDIOPATHIC PARKINSONS-DISEASE; RICHARDSON-OLSZEWSKI SYNDROME; MULTIPLE SYSTEM ATROPHY; FETAL MESENCEPHALIC TISSUE; STRIATAL FLUORODOPA UPTAKE; H-3 SPIPERONE BINDING; STRIATONIGRAL DEGENERATION AB Fluorodopa-PET (FD-PET) has proved to be an extremely useful technique for the noninvasive evaluation of nigrostriatal pathophysiology in patients with Parkinson's disease and other movement disorders. The development of ratio methods for image analysis has greatly reduced the complexity of these positron emission tomography studies and has facilitated data analysis. With the recent advances in cyclotron targetry and automated synthesis modules, FD-PET will soon become an important component of the clinical armamentarium. C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu NR 99 TC 14 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 2005 VL 43 IS 1 BP 93 EP + DI 10.1016/j.rcl.2004.08.002 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 881NZ UT WOS:000225875500008 PM 15693650 ER PT J AU Nimsky, C Ganslandt, O Hastreiter, P Wang, RP Benner, T Sorensen, AG Fahlbusch, R AF Nimsky, C Ganslandt, O Hastreiter, P Wang, RP Benner, T Sorensen, AG Fahlbusch, R TI Intraoperative diffusion-tensor MR imaging: Shifting of white matter tracts during neurosurgical procedures - Initial experience SO RADIOLOGY LA English DT Article ID BRAIN SHIFT; FUNCTIONAL NEURONAVIGATION; PYRAMIDAL TRACT; RESONANCE; TUMORS; MAGNETOENCEPHALOGRAPHY; VISUALIZATION; COMPENSATION; REGISTRATION; ANISOTROPY AB PURPOSE: To prospectively evaluate the location of white matter tracts with diffusion-tensor imaging (DTI) during neurosurgical procedures. MATERIALS AND METHODS: Ethical committee approval and signed informed consent were obtained. A 1.5-T magnetic resonance imager with an adapted rotating surgical table that is placed in a radiofrequency-shielded operating theater was used for pre- and intraoperative imaging. DTI was performed by applying an echo-planar imaging sequence with six diffusion directions in 38 patients (20 female patients, 18 male patients; age range, 7-77 years; mean age, 45.6 years) who were undergoing surgery (35 craniotomy and three burr hole procedures). Color-encoded maps of fractional anisotropy were generated by depicting white matter tracts. A rigid registration algorithm was used to compare pre- and intraoperative images. RESULTS: Intraoperative DTI was technically feasible in all patients, and no major image distortions occurred in the areas of interest. Pre- and intraoperative color-encoded maps of fractional anisotropy could be registered; these maps depicted marked and highly variable shifting of white matter tracts during neurosurgical procedures. In the 27 patients who underwent brain tumor resection, white matter tract shifting ranged from an inward shift of 8 mm to an outward shift of 15 mm (mean shift +/- standard deviation, outward shift of 2.5 mm +/- 5.8). In 16 (59%) of 27 patients, outward shifting was detected; in eight (30%), inward shifting was detected. In eight patients who underwent temporal lobe resections for drug-resistant epilepsy, shifting was only inward and ranged from 2 to 14 mm (9 mm +/- 3.3). In two of the three patients who underwent burr hole procedures, outward shifting occurred. CONCLUSION: Intraoperative DTI can depict shifting of major white matter tracts that is caused by surgical intervention. (C) RSNA, 2004. C1 Univ Erlangen Nurnberg, Dept Neurosurg, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr, Boston, MA 02114 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 FU NCRR NIH HHS [P41 RR1 14075, M01 RR 001066]; NINDS NIH HHS [NS 038477] NR 43 TC 125 Z9 143 U1 2 U2 4 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 JAN PY 2005 VL 234 IS 1 BP 218 EP 225 DI 10.1148/radiol.2341031984 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 881JW UT WOS:000225864800030 PM 15564394 ER PT S AU Kinner, B Capito, RM Spector, M AF Kinner, B Capito, RM Spector, M BE Yannas, IV TI Regeneration of articular cartilage SO REGENERATIVE MEDICINE II: CLINICAL AND PRECLINICAL APPLICATIONS SE Advances in Biochemical Engineering-Biotechnology LA English DT Article; Book Chapter DE articular cartilage; collagen; chondrocyte; joints; microfracture ID MESENCHYMAL STEM-CELLS; SMOOTH-MUSCLE ACTIN; AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; FULL-THICKNESS DEFECTS; GROWTH-FACTOR-I; OSTEOCHONDRAL DEFECTS; CANINE MODEL; MATRIX SYNTHESIS; CHONDRAL DEFECT; COLLAGEN GEL AB Loss of articular cartilage from the ends of bones forming diarthrodial joints can be the source of profound pain and disability, and eventually lead to complete degeneration of the joint, necessitating total joint replacement. Until a few years ago, there seemed little hope of treating such defects. Novel surgical procedures and cell therapies have recently been found, however, to stimulate the formation of reparative tissue resulting in the relief of pain and restoration of function, at least for a limited time period. Moreover, studies of the healing of chondral defects in animal models have revealed that there is some potential for regeneration of this connective tissue. The introduction of certain biomaterial scaffolds along with selected surgical procedures and cell therapies has been demonstrated in animal studies to facilitate the cartilage reparative process and now offers the promise of extending the longevity of clinical treatments of cartilage defects. Collectively these findings provide the basis for the rational development of approaches for the more complete regeneration of articular cartilage, and demonstrate that meaningful clinical outcomes can be achieved even if complete regeneration is not achieved. C1 Clin Univ Regensburg, Dept Trauma Surg, Regensburg, Germany. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Orthopaed Res Lab, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Kinner, B (reprint author), Clin Univ Regensburg, Dept Trauma Surg, Regensburg, Germany. EM drkinner@aol.com; rmc_16@mit.edu; mspector@rics.bwh.harvard.edu NR 120 TC 25 Z9 26 U1 3 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0724-6145 BN 3-540-22868-3 J9 ADV BIOCHEM ENG BIOT JI Adv. Biochem. Eng. Biotechnol. PY 2005 VL 94 BP 91 EP 123 DI 10.1007/b100001 PG 33 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BCC39 UT WOS:000228557400005 PM 15915870 ER PT S AU Hatton, MP Rubin, PAD AF Hatton, MP Rubin, PAD BE Yannas, IV TI Conjunctival regeneration SO REGENERATIVE MEDICINE II: CLINICAL AND PRECLINICAL APPLICATIONS SE Advances in Biochemical Engineering-Biotechnology LA English DT Article; Book Chapter ID GLAUCOMA FILTRATION SURGERY; AMNIOTIC MEMBRANE TRANSPLANTATION; CORNEAL SURFACE RECONSTRUCTION; FLUOROURACIL FILTERING SURGERY; STEM-CELL TRANSPLANTATION; GROWTH-FACTOR-BETA; MITOMYCIN-C; OCULAR-SURFACE; MUCOUS-MEMBRANE; IN-VITRO C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM eye_plastics@meei.harvard.edu NR 103 TC 6 Z9 6 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0724-6145 BN 3-540-22868-3 J9 ADV BIOCHEM ENG BIOT JI Adv. Biochem. Eng. Biotechnol. PY 2005 VL 94 BP 125 EP 140 DI 10.1007/b100002 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BCC39 UT WOS:000228557400006 PM 15915871 ER PT S AU Altshuler, D AF Altshuler, D BE Miyano, S Mesirov, J Kasif, S Istrail, S Pevzner, P Waterman, M TI Human genome sequence variation and the inherited basis of common disease SO RESEARCH IN COMPUTATIONAL MOLECULAR BIOLOGY, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 9th Annual International Conference on Research in Computational Molecular Biology (RECOMB 2005) CY MAY 14-18, 2005 CL Cambridge, MA SP Broad Inst MIT & Harvard, Boston Univ Ctr Adv Geonom Technol C1 MIT & Harvard, Broad Inst, Boston, MA 01224 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 01224 USA. RP Altshuler, D (reprint author), MIT & Harvard, Broad Inst, 50 Blossom St,Wellman 831, Boston, MA 01224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-25866-3 J9 LECT NOTES COMPUT SC PY 2005 VL 3500 BP 601 EP 602 PG 2 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Biochemistry & Molecular Biology; Computer Science GA BCK44 UT WOS:000229741100045 ER PT J AU Soroush-Yari, A Burstein, S Hoo, GWS Santiago, SM AF Soroush-Yari, A Burstein, S Hoo, GWS Santiago, SM TI Pulmonary hypertension in men with thyrotoxicosis SO RESPIRATION LA English DT Article DE dyspnea; hyperthyroidism; pulmonary hypertension ID GRAVES-DISEASE; TRICUSPID REGURGITATION; HYPERTHYROIDISM; HEART AB Thyrotoxicosis has a myriad of respiratory symptoms including dyspnea. Pulmonary hypertension may contribute to the respiratory symptoms of thyrotoxicosis, but is often unrecognized. We describe 3 male patients with thyrotoxicosis and associated pulmonary hypertension. Case reports of an additional 15 patients are also reviewed. In patients with thyrotoxicosis and pulmonary hypertension, treatment of thyrotoxicosis alone is associated with improvement in pulmonary hypertension. Previous reports have consisted of mostly female patients, but we report 3 men. When all cases are considered, the typical patient is female (10/14 = 71%), middle-aged ( 48 years), with mean pulmonary artery systolic pressures improving from 56 to 32 mm Hg with treatment. Autoantibodies were detected in 10/14 ( 71%) patients. The response to treatment ( medical or surgical) of thyrotoxicosis supports the hypothesis that hyperthyroidism is either a cause of pulmonary hypertension, or a factor that may unmask pulmonary hypertension. Recognition is important since treatment and response are very different compared to other patients with pulmonary hypertension. This association may not be readily considered in men, since most reports have been of women. Copyright (C) 2005 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med,Pulm & Crit Care Sect, Los Angeles, CA USA. RP Santiago, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect 111Q, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Silverio.santiago@med.va.gov NR 32 TC 12 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0025-7931 J9 RESPIRATION JI Respiration PY 2005 VL 72 IS 1 BP 90 EP 94 DI 10.1159/000083408 PG 5 WC Respiratory System SC Respiratory System GA 904ID UT WOS:000227488400017 PM 15753642 ER PT J AU Sarraf, D Jain, A Dubovy, S Kreiger, A Fong, D Paschal, J AF Sarraf, D Jain, A Dubovy, S Kreiger, A Fong, D Paschal, J TI Mucosa-associated lymphoid tissue lymphoma with intraocular involvement SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE choroidal infiltrates; conjunctival MALT lymphoma; intraocular neoplasm; MALT lymphoma; mucosa-associated lymphoid tissue lymphoma ID B-CELL LYMPHOMA; MALT LYMPHOMA; HYPERPLASIA; CONJUNCTIVITIS; SCLERITIS AB Purpose: To report the clinicopathologic features of a patient with mucosa-associated lymphoid tissue (MALT) lymphoma of the conjunctiva and associated intraocular involvement. Methods: This study is a retrospective clinicopathologic correlative case report summarizing the clinical, radiologic, and histopathologic findings of a patient with conjunctival MALT lymphoma and associated intraocular involvement. Results: Ophthalmic examination and fluorescein angiography demonstrated progressive conjunctival infiltration bilaterally, marked uveal effusions in the left eye, and cellular white infiltrates of the choroid in the right eye. MRI of the orbit revealed a diffusely infiltrating intra- and extraocular lesion extending around the globe and optic nerve in the left eye without evidence of intracranial extension. Conjunctival biopsy showed low-grade tumor cells, consistent with the diagnosis of MALT lymphoma. The patient was successfully treated with external beam radiation with marked clinical improvement. Conclusion: Conjunctival MALT lymphomas, typically indolent and localized tumors, may extend into the orbit and invade local tissues such as the choroid with devastating consequences. A conjunctival biopsy can provide an easy diagnosis of this treatable entity. C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Adm Healthcare Ctr, Los Angeles, CA USA. Kaiser Permanente, Baldwin Pk Woodland Hill, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33152 USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM dsarraf@ucla.edu NR 23 TC 25 Z9 26 U1 0 U2 2 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 JAN PY 2005 VL 25 IS 1 BP 94 EP 98 DI 10.1097/00006982-200501000-00018 PG 5 WC Ophthalmology SC Ophthalmology GA 891OG UT WOS:000226589800018 PM 15655452 ER PT J AU Altfeld, M AF Altfeld, Marcus TI HIV-1-specific T cell function during acute HIV-1 infection SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Altfeld, Marcus] Massachusetts Gen Hosp, Res Ctr, Boston, MA 02129 USA. [Altfeld, Marcus] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. [Altfeld, Marcus] Harvard Univ, Sch Med, Div Aids, Boston, MA 02129 USA. EM maltfeld@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S104 DI 10.1186/1742-4690-2-S1-S104 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600181 ER PT J AU Lieberman, J AF Lieberman, Judy TI The kiss of death: A new model for how perforin delivers granzymes to target cells SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Lieberman, Judy] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. EM lieberman@cbr.med.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S106 DI 10.1186/1742-4690-2-S1-S106 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600182 ER PT J AU Zamborlini, A Usami, Y Radoshitzky, S Popova, E Palu, G Gottlinger, H AF Zamborlini, Alessia Usami, Yoshiko Radoshitzky, Sheli Popova, Elena Palu, Giorgio Gottlinger, Heinrich TI Regulation of host factors involved in HIV budding through autoinhibition SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Zamborlini, Alessia; Usami, Yoshiko; Popova, Elena; Gottlinger, Heinrich] UMass Med Sch, Dept Mol Med, Worcester, MA USA. [Zamborlini, Alessia; Usami, Yoshiko; Popova, Elena; Gottlinger, Heinrich] UMass Med Sch, Program Gene Funct & Express, Worcester, MA USA. [Radoshitzky, Sheli] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palu, Giorgio] Univ Padua, Inst Microbiol, Padua, Italy. EM heinrich.gottlinger@umassmed.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2005 VL 2 SU 1 AR S147 DI 10.1186/1742-4690-2-S1-S147 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600211 ER PT J AU Mao, JR AF Mao, JR TI Central glucocorticoid receptor: A new role in the cellular mechanisms of neuropathic pain SO REVIEWS IN THE NEUROSCIENCES LA English DT Article DE glucocorticoid receptor; NMDA receptor; neuropathic pain; nerve injury; interleukin; protein kinase C; mitogen-activated protein kinase ID PERIPHERAL-NERVE INJURY; REDUCE NOCICEPTIVE BEHAVIORS; CHRONIC CONSTRICTION INJURY; SUPERFICIAL DORSAL HORN; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA LEVELS; SPINAL-CORD; MOLECULAR-MECHANISMS; PROINFLAMMATORY CYTOKINES; MORPHINE-TOLERANCE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pain Med,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pain Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pain Med,Dept Anesthesia & Crit Care, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NINDS NIH HHS [R01 NS42661] NR 73 TC 1 Z9 3 U1 0 U2 1 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 IS 3 BP 233 EP 238 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 985LM UT WOS:000233379000004 PM 16329195 ER PT J AU Amedi, A Bermpohl, F Camprodon, J Merabet, L Meijer, F Pascual-Leone, A AF Amedi, A Bermpohl, F Camprodon, J Merabet, L Meijer, F Pascual-Leone, A TI Neural correlates of visual-to-auditory sensory substitution in proficient blind users. SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurol, Ctr Noninvas Brain Stim,BIDMC, Boston, MA 02115 USA. Philips Res, Eindhoven, Netherlands. RI Ronen, Itamar/E-8518-2016 OI Ronen, Itamar/0000-0002-6872-4895 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S2 EP S2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100007 ER PT J AU Amedi, A Camprodon, J Ronen, I Kim, D Pascual-Leone, A AF Amedi, A Camprodon, J Ronen, I Kim, D Pascual-Leone, A TI TMS during fMRI to study connectivity and the neural correlates of visual awareness. SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurol, Ctr Non Invas Brain Stim,BIDMC, Boston, MA USA. Boston Univ, Ctr Biomed Imaging, Boston, MA 02215 USA. RI Ronen, Itamar/E-8518-2016 OI Ronen, Itamar/0000-0002-6872-4895 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S2 EP S2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100006 ER PT J AU Amedi, A Malach, R Pascual-Leone, A AF Amedi, A Malach, R Pascual-Leone, A TI Negative BOLD differentiates visual imagery and perception SO REVIEWS IN THE NEUROSCIENCES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Neurol, Ctr Noninvas Brain Stim,BIDMC, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RI Ronen, Itamar/E-8518-2016 OI Ronen, Itamar/0000-0002-6872-4895 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2005 VL 16 SU 1 BP S2 EP S2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 991HU UT WOS:000233804100008 ER PT J AU Felson, DT Gale, DR Elon Gale, M Niu, J Hunter, DJ Goggins, J LaValley, MP AF Felson, DT Gale, DR Elon Gale, M Niu, J Hunter, DJ Goggins, J LaValley, MP TI Osteophytes and progression of knee osteoarthritis SO RHEUMATOLOGY LA English DT Article DE knee osteoarthritis; osteophyte; natural history; biomechanics; alignment ID JOINT SPACE WIDTH; DISEASE; SIZE AB Objectives. Osteophytes are thought to stabilize an osteoarthritic joint, thereby preventing structural progression. Meagre longitudinal data suggest, however, that they are associated with an increased risk of structural progression. Our objective was to evaluate the effect of osteophyte size on radiographic progression in osteoarthritis (OA). Methods. Using data from a natural history study of persons with symptomatic knee OA, we obtained fluoroscopically positioned postero-anterior (PA) radiographs at baseline, 15 and 30 months. Using an atlas, osteophyte size was scored on a scale of 0-3 at each of four sites on the PA film and, for each knee, both compartment-specific (i.e. medial; lateral) and overall osteophyte scores were computed. Progression was defined as an increase over follow-up in medial or lateral joint space narrowing, based on a semiquantitative grading. Mechanical alignment was assessed using long limb films at the 15 month examination. Logistic regression was used to evaluate the relation of osteophyte size with progression, adjusting for age, gender and body mass index, and with and without adjustment for alignment. Results. Of 270 subjects who had 470 eligible knees with follow-up, 104 (22%) knees showed progression. Overall, osteophyte score modestly increased the risk of progression [odds ratio (OR) per s.d. increase of osteophyte score = 1.4 (95% CI 1.1, 1.8, P = 0.02)], but this effect weakened and became non-significant after adjustment for limb alignment (OR = 1.3). Compartment osteophyte score was strongly associated with malalignment to the side of the osteophyte (e.g. medial osteophyte and varus). Compartment-specific osteophyte score markedly increased the risk of ipsilateral progression (e.g. medial osteophytes --> medial progression) [OR per s.d. = 1.9 (95% CI 1.5, 2.5, P<0.001)] and decreased the risk of contralateral progression [OR per s.d. = 0.6 (95% CI 0.5, 0.8, P = 0.002)], but these associations diminished when we adjusted for limb alignment (OR = 1.5 and 0.7 respectively). Conclusions. Large osteophytes do not affect the risk of structural progression. They are strongly associated with malalignment to the side of the osteophyte, and any relation they have with progression is partly explained by the association of malalignment with progression. C1 Boston Univ, Sch Med, Ctr Arthritis, Boston, MA 02118 USA. Boston Univ, Clin Epidemiol Res & Traing Unit, Boston, MA 02215 USA. VA Boston Hlth Care Syst, Boston, MA USA. RP Felson, DT (reprint author), Boston Univ, Sch Med, Ctr Arthritis, 715 Albany St,A207, Boston, MA 02118 USA. EM dfelson@bu.edu RI Hunter, David/A-4622-2010; OI Hunter, David/0000-0003-3197-752X; Felson, David/0000-0002-2668-2447; Niu, Jingbo/0000-0002-6170-1965; LaValley, Michael/0000-0002-8488-5170 FU NIAMS NIH HHS [AR47785] NR 18 TC 60 Z9 66 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD JAN PY 2005 VL 44 IS 1 BP 100 EP 104 DI 10.1093/rheumatology/keh411 PG 5 WC Rheumatology SC Rheumatology GA 885WF UT WOS:000226187300018 PM 15381791 ER PT J AU Clarke, P Richardson-Burns, SM DeBiasi, RL Tyler, KL AF Clarke, P Richardson-Burns, SM DeBiasi, RL Tyler, KL TI Mechanisms of apoptosis during reovirus infection SO ROLE OF APOPTOSIS IN INFECTION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; CENTRAL-NERVOUS-SYSTEM; ATTACHMENT PROTEIN SIGMA-1; SPINAL MUSCULAR-ATROPHY; CELL-CYCLE ARREST; STRUCTURAL BASIS; DEATH RECEPTORS; GENE-EXPRESSION; CANCER-CELLS; SIALIC-ACID AB Reovirus infection has proven to be an excellent experimental system for studying mechanisms of virus-induced pathogenesis. Reoviruses induce apoptosis in a wide variety of cultured cells in vitro and in target tissues in vivo, including the heart and central nervous system. In vivo, viral infection, tissue injury, and apoptosis colocalize, suggesting that apoptosis is a critical mechanism by which disease is triggered in the host. This review examines the mechanisms of reovirus-induced apoptosis and investigates the possibility that inhibition of apoptosis may provide a novel strategy for limiting virus-induced tissue damage following infection. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80220 USA. RP Clarke, P (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, 4200 E 9th Ave, Denver, CO 80262 USA. EM Penny.Clarke@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS050138, R01 NS050138-04, R01 NS051403, R01 NS051403-03, R01NS050138] NR 48 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2005 VL 289 BP 1 EP 24 PG 24 WC Immunology; Microbiology SC Immunology; Microbiology GA BCT25 UT WOS:000231113700001 PM 15791949 ER PT J AU Buchanan, RW Davis, M Goff, D Green, MF Keefe, RSE Leon, AC Nuechterlein, KH Laughren, T Levin, R Stover, E Fenton, W Marder, SR AF Buchanan, RW Davis, M Goff, D Green, MF Keefe, RSE Leon, AC Nuechterlein, KH Laughren, T Levin, R Stover, E Fenton, W Marder, SR TI A summary of the FDA-NIMH-MATRICS Workshop on Clinical Trial Design for Neurocognitive Drugs for Schizophrenia. SO SCHIZOPHRENIA BULLETIN LA English DT Article ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; PLACEBO-CONTROLLED TRIAL; AFFECTIVE-DISORDER; SCHIZOAFFECTIVE DISORDER; ANTIPSYCHOTIC TREATMENT; COGNITIVE DYSFUNCTION; PSYCHIATRIC-SYMPTOMS; NEGATIVE SYMPTOMS; D-CYCLOSERINE; MISSING DATA AB Objective: On April 23, 2004, a joint meeting of the FDA, NIMH, MATRICS investigators, and experts from academia and the pharmaceutical industry was convened to develop guidelines for the design of clinical trials of cognitive-enhancing drugs for neurocognitive impairments in patients with schizophrenia. Method: Experts were asked to address specific questions relating to clinical trial design of adjunctive/co-treatment and broad spectrum agents. At the workshop, experts reviewed relevant evidence before offering the discussion panel proposed in guidlines for a given subset of questions. The discussion panel, which consisted of presenters and representatives from FDA, NIMH, academia, and industry, deliberated to reach consensus on suggested guidelines. When evidence was insufficient, suggested guidelines represent the opinion of a cross-section of the presenters and discussion panel. Results: Guidelines were developed for inclusion criteria, the use of co-primary outcome measures, and statistical approaches for study design. Consensus was achieved regarding diagnostic and concomitant medication inclusion criteria and on the use of cognitive screening measures. A key guideline was to limit the trial to patients in the residual phase of their illness, who have a predefined level of positive, negative, and affective symptoms. The most difficult issues were the feasibility of including a co-primary measure of functional improvement and the choice of comparator agent for a trial of a broad spectrum agent (with antipsychotic and cognitive-enhancing effects). Conclusions: The suggested guidelines represent reasonable starting points for trial design of cognitive-enhancing drugs, with the understanding that new data, subsequent findings, or other methodological considerations may lead to future modifications. C1 Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC 20052 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, VISN 22 Mental Illness Res Educ Clin Ctr, Los Angeles, CA USA. Duke Univ, Ctr Med, Durham, NC 27706 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Publ Hlth, New York, NY 10021 USA. RP Buchanan, RW (reprint author), Maryland Psychiat Res Ctr, POB 21247, Catonsville, MD 21228 USA. EM RWBuchanan@mpre.umaryland.edu FU NIMH NIH HHS [MH22006] NR 93 TC 269 Z9 275 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2005 VL 31 IS 1 BP 5 EP 19 DI 10.1093/schbul/sbi020 PG 15 WC Psychiatry SC Psychiatry GA 915MV UT WOS:000228309200003 PM 15888422 ER PT J AU Sergi, MJ Kern, RS Mintz, J Green, MF AF Sergi, MJ Kern, RS Mintz, J Green, MF TI Learning potential and the prediction of work skill acquisition in schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; learning potential; dynamic testing; neurocognition; work skills; vocational skills ID CARD SORTING TEST; NEUROCOGNITIVE DEFICITS; REHABILITATION; PERFORMANCE; DEMENTIA; CAPACITY AB This study examined whether a measure of learning potential could predict work skill acquisition in schizophrenia beyond the prediction offered by a single administration assessment. Fifty-seven outpatients with schizophrenia or schizoaffective disorder completed a test-train-test version of the Wisconsin Card Sorting Test as a measure of their learning potential. The outpatients were randomly assigned to training by errorless learning or conventional instruction on two work skills (index card filing and toilet tank assembly). Work skills were assessed both immediately and 3 months after training. Generally, patients with high learning potential performed better on the work skill tasks. Learning potential explained an additional 15 percent of variance beyond single administration assessment in participants' accuracy immediately after work skill training and an additional 13 percent of variance in participants' accuracy 3 months after training. These findings indicate that measures of learning potential contribute to the prediction of work skill acquisition, going beyond the predictive power of single administration assessments. C1 Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sergi, MJ (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM mark.sergi@csun.edu FU NIMH NIH HHS [MH-30911] NR 17 TC 38 Z9 43 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2005 VL 31 IS 1 BP 67 EP 72 DI 10.1093/schbul/sbi007 PG 6 WC Psychiatry SC Psychiatry GA 915MV UT WOS:000228309200007 PM 15888426 ER PT J AU Bowie, CR Serper, MR Riggio, S Harvey, PD AF Bowie, CR Serper, MR Riggio, S Harvey, PD TI Neurocognition, symptomatology, and functional skills in older alcohol-abusing schizophrenia patients SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; alcohol; cognition; adaptive functions ID GERIATRIC-PATIENTS; VOLUME DEFICITS; COMORBIDITY; DYSFUNCTION; IMPAIRMENT; INSTRUMENT; MEDICATION; DEPENDENCE; DISORDERS; DIAGNOSIS AB Deficits in neurocognitive functioning are common to both schizophrenia and alcoholism. Recent studies suggest that neurocognitive functioning is the most significant predictor of social-adaptive functioning in schizophrenia. Cognitive impairment induced by alcoholism may result in more impaired functional outcome for comorbid patients. Past research examining alcohol-abusing schizophrenia patients has not examined correlates with functional outcome and has generally been limited to relatively younger patients. This study examined neurocognitive functioning and its correlates in alcohol-abusing schizophrenia patients between the ages of 40 and 80. Outpatients with schizophrenia (SZ; n = 17) or both schizophrenia and alcohol abuse or dependence (SZ + ETOH; n = 18) were tested on a neurocognitive battery, rated for symptomatology, and assessed for functional abilities. The results suggest that alcohol abuse in schizophrenia is associated with more impaired functioning across many domains, including memory impairment, negative and general psychopathology symptoms, and adaptive functions. The only significant predictor of impaired functional status in the overall sample and the SZ + ETOH group was neurocognitive functioning. C1 Mt Sinai Sch Med, Dept Psychiat, Psychol Serv, New York, NY 10029 USA. Hofstra Univ, Dept Psychol, Hempstead, NY 11550 USA. NYU, Sch Med, New York, NY USA. Mt Sinai Sch Med, Schizophrenia Treatment & Res Program, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY 10029 USA. RP Bowie, CR (reprint author), Mt Sinai Sch Med, Dept Psychiat, Psychol Serv, 1425 Madison Ave,4th Floor, New York, NY 10029 USA. EM christopher.bowie@mssm.edu RI Reis, Aline/G-9573-2012 FU NIMH NIH HHS [MH 36692, MH63116] NR 41 TC 32 Z9 32 U1 4 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2005 VL 31 IS 1 BP 175 EP 182 DI 10.1093/schbul/sbi001 PG 8 WC Psychiatry SC Psychiatry GA 915MV UT WOS:000228309200016 PM 15888435 ER PT J AU Yao, JK Thomas, EA Reddy, RD Keshavan, MS AF Yao, JK Thomas, EA Reddy, RD Keshavan, MS TI Association of plasma apolipoproteins D with RBC membrane arachidonic acid levels in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE apolipoproteins D; arachidonic acid; schizophrenia; first-episode neuroleptic-naive ID PSYCHIATRIC-DISORDERS; HUMAN ERYTHROCYTES; OXIDATIVE-STRESS; RAT HIPPOCAMPUS; E EXPRESSION; BRAIN; DISEASE; FLUID; PATHOPHYSIOLOGY; PROGESTERONE AB Apolipoprotein D (apoD) is a member of the lipocalin superfamily of transporter proteins that bind small hydrophobic molecules, including arachidonic acid (AA). The ability of apoD to bind AA implicates it in pathways associated with membrane phospholipid signal transduction and metabolism. Recent findings of an increased expression of apoD in the mouse brain after clozapine treatment suggested a role for apoD in the pharmacological action of clozapine. Moreover, clozapine has been shown to increase membrane AA levels in RBC phospholipids from schizophrenic patients. ApoD levels have also been shown to be elevated in the CNS of subjects with chronic schizophrenia, a disorder associated with AA dysfunction. In this study, we examined whether plasma apoD levels are related to red blood cell membrane AA contents in the first episode neuroleptic-naive schizophrenic (FENNS) patients. Plasma apoD levels as measured by enzyme-linked immunosorbent (ELISA) were not significantly different (F = 0.51, df = 2,86, p = 0.60) among healthy controls (n = 36). FENNS patients (n = 33) and patients with other psychiatric disorders (n = 19). However, plasma apoD levels were significantly correlated with RBC-AA (p = 0.0022) and docosapentaenoic acid (p = 0.0008) in FENNS patients. There are several known mechanisms that can lead to the type of membrane fatty acid defects that have been identified in schizophrenia. Whether plasma apoD alone is a major determinant of reduced RBC membrane AA levels in FENNS patients remains to be determined, although these preliminary data appear not to support this prentise. Taken together with other in vitro studies, however, the present data support the view, that an increased expression of apoD such as induced by atypical neuroleptic drug, may facilitate incorporation of AA into membrane phospholipids by its selective binding to AA. (C) 2004 Elsevier B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Neurochem & Psychopharm Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Ctr Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Neurochem & Psychopharm Lab, Bldg 13,1780 Highland Dr, Pittsburgh, PA 15206 USA. EM jkyao@pitt.edu FU NIMH NIH HHS [MH-64118, MH-45203, MH-58141] NR 41 TC 13 Z9 15 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 JAN 1 PY 2005 VL 72 IS 2-3 BP 259 EP 266 DI 10.1016/j.schres.2004.05.007 PG 8 WC Psychiatry SC Psychiatry GA 889FZ UT WOS:000226430200017 PM 15560970 ER PT S AU Kandasamy, N Abdelwahed, S Sharp, GC Hayes, JP AF Kandasamy, N Abdelwahed, S Sharp, GC Hayes, JP BE Babaoglu, O Jelasity, M Montresor, A Fetzer, C Leonardi, S VanMoorsel, A VanSteen, M TI An online control framework for designing self-optimizing computing systems: Application to power management SO SELF-STAR PROPERTIES IN COMPLEX INFORMATION SYSTEMS: CONCEPTUAL AND PRACTICAL FOUNDATIONS SE Lecture Notes in Computer Science LA English DT Article ID ALGORITHMS AB Computer systems hosting critical e-commerce applications must typically satisfy stringent quality-of-service (QoS) requirements under dynamic operating conditions and workloads. Also, as such systems increase in size and complexity, maintaining the desired QoS by manually tuning the numerous performance-related parameters will become very difficult. This paper addresses the design of self-optimizing computer systems using a generic online control framework in which the control actions governing the operation of the system are obtained by optimizing its behavior, as forecast by a mathematical model, over a limited time horizon. As a specific application of this control technique, we show how to minimize the power consumed by a processor while satisfying the QoS requirements of a time-varying workload. We describe the processor model, formulate the power management problem, and derive the online control algorithm. The performance of the controller is evaluated using representative e-commerce workloads. C1 Drexel Univ, Elect & Comp Engn Dept, Philadelphia, PA 19104 USA. Vanderbilt Univ, Inst Software Integrated Syst, Nashville, TN 37212 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Elect & Comp Engn Dept, Ann Arbor, MI 48109 USA. RP Drexel Univ, Elect & Comp Engn Dept, Philadelphia, PA 19104 USA. EM kandasamy@ece.drexel.edu; sherif@isds.vanderbilt.edu; gcsharp@partners.org; jhayes@eecs.umich.edu OI Abdelwahed, Sherif/0000-0002-6355-4671 NR 28 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-26009-9 J9 LECT NOTES COMPUT SC PY 2005 VL 3460 BP 174 EP 188 PG 15 WC Computer Science, Theory & Methods SC Computer Science GA BCQ56 UT WOS:000230782300012 ER PT J AU Shipley, WU Zietman, AL Kaufman, DS Coen, JJ Sandler, HM AF Shipley, WU Zietman, AL Kaufman, DS Coen, JJ Sandler, HM TI Selective bladder preservation by trimodality therapy for patients with muscularis propria-invasive bladder cancer and who are cystectomy candidates - The Massachusetts General Hospital and Radiation Therapy Oncology Group Experiences SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PHASE I-II; TRANSURETHRAL RESECTION; ORGAN PRESERVATION; CISPLATIN; CHEMOTHERAPY; CARCINOMA; CONSERVATION; GEMCITABINE; TRIAL; IRRADIATION C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02138 USA. RP Zietman, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02138 USA. NR 20 TC 37 Z9 38 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2005 VL 15 IS 1 BP 36 EP 41 DI 10.1016/j.semradone.2004.07.008 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 894WI UT WOS:000226821900006 PM 15662605 ER PT J AU Zietman, A Skinner, E AF Zietman, A Skinner, E TI Quality of life after radical treatment for invasive bladder cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID URINARY-DIVERSION; ILEAL CONDUIT; CYSTECTOMY; CARCINOMA; QUESTIONNAIRE; SUBSTITUTION; THERAPY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Keck Univ So Calif, Sch Med, Dept Urol, Los Angeles, CA USA. RP Skinner, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 18 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JAN PY 2005 VL 15 IS 1 BP 55 EP 59 DI 10.1016/j.semradone.2004.07.013 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 894WI UT WOS:000226821900009 PM 15662608 ER PT J AU Reddy, GP Gotway, MB Araoz, PA AF Reddy, GP Gotway, MB Araoz, PA TI Imaging of chronic thromboembolic pulmonary hypertension SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CT FINDINGS; SPIRAL CT; HELICAL CT; EMBOLISM; ANGIOGRAPHY; DIAGNOSIS; CONTRAST; DISEASE C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Mayo Clin, Dept Radiol, Rochester, MN USA. RP Reddy, GP (reprint author), Univ Calif San Francisco, Dept Radiol, Box 0628,505 Parnassus Ave,Suite M396, San Francisco, CA 94143 USA. EM gautham.reddy@radiology.uscf.edu NR 20 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JAN PY 2005 VL 40 IS 1 BP 41 EP 47 DI 10.1053/j.ro.2004.09.009 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 889YT UT WOS:000226479500009 PM 15732560 ER PT J AU Mu, QW Nahas, Z Johnson, KA Yamanaka, K Mishory, A Koola, J Hill, S Horner, MD Bohning, DE George, MS AF Mu, QW Nahas, Z Johnson, KA Yamanaka, K Mishory, A Koola, J Hill, S Horner, MD Bohning, DE George, MS TI Decreased cortical response to verbal working memory following sleep deprivation SO SLEEP LA English DT Article DE verbal working memory; sleep deprivation; functional magnetic resonance imaging ID TERM RECOGNITION MEMORY; BRAIN-REGIONS; TASK; MAINTENANCE; PERFORMANCE; ACTIVATION; COMPONENTS; ATTENTION; BEHAVIOR; HUMANS AB Study Objective: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. Design: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. Setting: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. Patients or Participants: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. Interventions: None. Measurements and Results: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. Conclusions: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the parietal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability. C1 Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Mu, QW (reprint author), Med Univ S Carolina, Brain Stimulat Lab, IOP,502 N,67 President St, Charleston, SC 29425 USA. EM muq@musc.edu FU NIA NIH HHS [R01-AG40956] NR 34 TC 77 Z9 82 U1 0 U2 5 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2005 VL 28 IS 1 BP 55 EP 67 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 911TN UT WOS:000228028000010 PM 15700721 ER PT J AU Littner, MR Kushida, C Wise, M Davila, DG Morgenthaler, T Lee-Chiong, T Hirshkowitz, M Loube, DL Bailey, D Berry, RB Kapen, S Kramer, M AF Littner, MR Kushida, C Wise, M Davila, DG Morgenthaler, T Lee-Chiong, T Hirshkowitz, M Loube, DL Bailey, D Berry, RB Kapen, S Kramer, M TI Practice Parameters for clinical use of the multiple sleep latency test and the maintenance of wakefulness test - An American Academy of Sleep Medicine Report - Standards of practice committee of the American Academy of Sleep Medicine SO SLEEP LA English DT Article DE multiple sleep latency test; maintenance of wakefulness test; sleepiness; hypersomnia; daytime wakefulness ID EXCESSIVE DAYTIME SLEEPINESS; NARCOLEPSY; APNEA AB Characterization of excessive sleepiness is an important task for the sleep clinician, and assessment requires a thorough history and in many cases, objective assessment in the sleep laboratory. These practice parameters were developed to guide the sleep clinician on appropriate clinical use of the Multiple Sleep Latency Test (MSLT), and the Maintenance of Wakefulness Test (MWT). These recommendations replace those published in 1992 in a position paper produced by the American Sleep Disorders Association. A Task Force of content experts was appointed by the American Academy of Sleep Medicine to perform a comprehensive review of the scientific literature and grade the evidence regarding the clinical use of the MSLT and the MWT Practice parameters were developed based on this review and in most cases evidence based methods were used to support recommendations. When data were insufficient or inconclusive, the collective opinion of experts was used to support recommendations. These recommendations were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. The MSLT is indicated as part of the evaluation of patients with suspected narcolepsy and may be useful in the evaluation of patients with suspected idiopathic hypersomnia. The MSLT is not routinely indicated in the initial evaluation and diagnosis of obstructive sleep apnea syndrome, or in assessment of change following treatment with nasal continuous positive airway pressure (CPAP). The MSLT is not routinely indicated for evaluation of sleepiness in medical and neurological disorders (other than narcolepsy), insomnia, or circadian rhythm disorders. The MWT may be indicated in assessment of individuals in whom the inability to remain awake constitutes a safety issue, or in patients with narcolepsy or idiopathic hypersomnia to assess response to treatment with medications. There is little evidence linking mean sleep latency on the MWT with risk of accidents in real world circumstances. For this reason, the sleep clinician should not rely solely on mean sleep latency as a single indicator of impairment or risk for accidents, but should also rely on clinical judgment. Assessment should involve integration of findings from the clinical history, compliance with treatment, and, in some cases, objective testing using the MWT These practice parameters also include recommendations for the MSLT and MWT protocols, a discussion of the normative data available for both tests, and a description of issues that need further study. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. David Geffen Sch Med, Sepulveda, CA USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baptist Med Ctr, Sleep Disorders Ctr, Little Rock, AR USA. Mayo Sleep Disorders Ctr, Rochester, MN USA. Natl Jewish Med & Res Ctr, Sleep Clin, Denver, CO USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Swedish Med Ctr, Sleep Med Inst, Seattle, WA USA. Univ Florida, Malcolm Randall VAMC, Gainesville, FL USA. Wayne State Univ, Detroit, MI USA. Maimonides Hosp, Dept Psychiat, Brooklyn, NY 11219 USA. NYU, Sch Med, New York, NY USA. RP Littner, MR (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. OI Morgenthaler, Timothy/0000-0002-2614-3793 NR 18 TC 374 Z9 380 U1 2 U2 12 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JAN 1 PY 2005 VL 28 IS 1 BP 113 EP 121 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 911TN UT WOS:000228028000016 PM 15700727 ER PT J AU Atwood, C Simpson, R Konermann, M Cramer-Borneman, M Shalaby, A Freedman, RA Fowler, J Hansen, C Neuzner, J Hartley, J AF Atwood, C Simpson, R Konermann, M Cramer-Borneman, M Shalaby, A Freedman, RA Fowler, J Hansen, C Neuzner, J Hartley, J TI Atrial overdrive pacing & sleep apnea in a bradycardia population SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Utah, Salt Lake City, UT USA. Klinikum Kassel, Kassel, Germany. Marien Hosp, Kassel, Germany. Hennepin Cty Med Ctr, Minneapolis, MN USA. Guidant Corp, CRM, St Paul, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 579 BP A195 EP A195 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101088 ER PT J AU Fins, A Hardy, M Baker, T Danser, A Patel, E Walker, L Farrow, H AF Fins, A Hardy, M Baker, T Danser, A Patel, E Walker, L Farrow, H TI Cognitive behavioral therapy for HIV-related insomnia SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Nova SE Univ, Ctr Psychol Studies, Ft Lauderdale, FL 33314 USA. VA Boston Healthcare Syst, Boston, MA USA. Emery Behav Med, Weston, ACT, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 699 BP A235 EP A235 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101207 ER PT J AU Fischer, ME Watson, NF Buchwald, D Vitek, M Goldberg, J AF Fischer, ME Watson, NF Buchwald, D Vitek, M Goldberg, J TI Sleep duration and self-reported illness in twins SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, VET Registry, Seattle ERIC, Seattle, WA USA. Hines VA Cooperat Studies Program, Hines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 453 BP A154 EP A154 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100455 ER PT J AU Hirshkowitz, M Roth, T Black, J Wesnes, K Arora, S Niebler, G White, D AF Hirshkowitz, M Roth, T Black, J Wesnes, K Arora, S Niebler, G White, D TI Armodafinil as adjunct therapy improves wakefulness and fatigue in patients with obstructive sleep apnea/hypopnea syndrome SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 VA Med Ctr, Sleep Disorders Ctr, Houston, TX USA. Henry Ford Hosp, Sleep Disorders & Res Ctr, Detroit, MI 48202 USA. Stanford Univ, Stanford Sleep Disorders Clin, Stanford, CA 94305 USA. Cognit Drug Res Ltd, Goring On Thames, England. Cephalon Inc, W Chester, PA USA. Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 531 BP A180 EP A180 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101040 ER PT J AU Jordan, AS Schoory, K Dover, L Fogel, RB Malhotra, A White, DP AF Jordan, AS Schoory, K Dover, L Fogel, RB Malhotra, A White, DP TI Genioglossal responsiveness to decreasing CPAP during stable NREM sleep SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Brigham & Womens Hosp, BIDMC, Sleep Disorders Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 512 BP A173 EP A174 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101021 ER PT J AU Krystal, A Rubens, R Fava, M McCall, V Wessel, T Amato, D Caron, J Roth, T AF Krystal, A Rubens, R Fava, M McCall, V Wessel, T Amato, D Caron, J Roth, T TI Eszopiclone co-administered with fluoxetine for insomnia associated with major depressive disorder (MDD): Effects following eszopiclone discontinuation SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Duke Univ, Med Ctr, Durham, NC USA. Sepracor Inc, Marlborough, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Henry Ford Sleep Disorders Ctr, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 918 BP A311 EP A311 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101426 ER PT J AU Lu, JW Mann, GL Volgin, DV Ross, RJ Morrison, AR Kubin, L AF Lu, JW Mann, GL Volgin, DV Ross, RJ Morrison, AR Kubin, L TI Perifornical hypothalamic microinjections of antisense oligodeoxynucleotides against beta 3 subunit of GABA(A) receptor reduce REM sleep SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Penn, Dept Biol Anim, Philadelphia, PA 19104 USA. Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. RI Volgin, Denys/A-1041-2007 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 28 BP A10 EP A10 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100030 ER PT J AU Martin, JL Webber, AP Harker, JO Josephson, KR Alessi, CA AF Martin, JL Webber, AP Harker, JO Josephson, KR Alessi, CA TI Diurnal cortisol is associated with functional improvement during post-acute rehabilitation in older adults SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 328 BP A111 EP A112 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100329 ER PT J AU McCall, V Fava, M Wessell, T Rubens, R Caron, J Amato, D Roth, T AF McCall, V Fava, M Wessell, T Rubens, R Caron, J Amato, D Roth, T TI Eszopiclone co-administered with fluoxetine for insomnia associated with major depressive disorder (MDD): An analysis of the effects on depression SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sepracor Inc, Marlborough, MA USA. Henry Ford Sleep Disorders Ctr, Detroit, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 916 BP A310 EP A310 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101424 ER PT J AU Pawlyk, AC Ross, RJ Jha, SK Brennan, FX Morrison, AR AF Pawlyk, AC Ross, RJ Jha, SK Brennan, FX Morrison, AR TI The differential rapid eye movement sleep response to cued and contextual fear conditioning is suppressed by a shared response to fearful conditioned stimuli SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Univ Penn, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 1020 BP A346 EP A346 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101527 ER PT J AU Ramesh, V McCarley, RW Basheer, R AF Ramesh, V McCarley, RW Basheer, R TI Age related changes in basal forebrain cholinergic neurons: A morphological and EEG power spectral study SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Harvard Univ, Sch Med, W Roxbury, MA USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 7 BP A3 EP A3 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100009 ER PT J AU Scheer, FA Zeitzer, JM Ayas, NT Brown, R Czeisler, CA Shea, SA AF Scheer, FA Zeitzer, JM Ayas, NT Brown, R Czeisler, CA Shea, SA TI Reduced sleep efficiency in cervical spinal cord injury; Association with abolished nighttime melatonin secretion SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Sleep Med, Boston, MA 02115 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Vancouver Gen Hosp, Dept Med, Ctr Clin Epidemiol & Evaluat, Vancouver, BC, Canada. Massachusetts Gen Hosp, Pulm & Clin Care Unit, Boston, MA 02114 USA. RI Scheer, Frank/C-2795-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 202 BP A68 EP A68 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100203 ER PT J AU Szymusiak, R Xi, X Kumar, S Shah, N McGinty, D AF Szymusiak, R Xi, X Kumar, S Shah, N McGinty, D TI Activation of arousal systems during sleep in rats exposed to intermittent hypoxia SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 79 BP A26 EP A26 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100081 ER PT J AU Tucker, AM Gehrman, P Sanford, LD Morrison, AR Armitage, R Ross, RJ AF Tucker, AM Gehrman, P Sanford, LD Morrison, AR Armitage, R Ross, RJ TI Effect of anticipatory anxiety on sleep SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Sci Philadelphia, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 928 BP A314 EP A314 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101436 ER PT J AU Uschakov, A McGinty, D Szymusiak, R AF Uschakov, A McGinty, D Szymusiak, R TI Sleep active neurons within the ventral lamina terminalis project to the bed nucleus of the stria terminalis and the lateral hypothalamus SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 51 BP A17 EP A17 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100053 ER PT J AU Ward, CP McCoy, JG Tartar, JL McKenna, JT McCarley, RW Strecker, RE AF Ward, CP McCoy, JG Tartar, JL McKenna, JT McCarley, RW Strecker, RE TI Hippocampal-dependent memory in a rat model of obstructive sleep apnea SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Stonehill Coll, Easton, PA USA. Univ So Mississippi, Hattiesburg, MS 39406 USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. VA Boston Healthcare Syst, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 21 BP A7 EP A7 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100023 ER PT J AU Weaver, EM AF Weaver, EM TI Self-identified sleep apnea is associated with subjective sleepiness SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Univ Washington, Sleep Disorders Ctr, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 620 BP A208 EP A208 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101129 ER PT J AU Winkelman, JW Johnston, L Fava, M AF Winkelman, JW Johnston, L Fava, M TI Restless legs syndrome in treated depressed outpatients: Prevalence and clinical correlates SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 782 BP A263 EP A263 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906101290 ER PT J AU Xi, X McGinty, D Szymusiak, R AF Xi, X McGinty, D Szymusiak, R TI Patterns of sleep disturbance in rats exposed to intermittent hypoxia SO SLEEP LA English DT Meeting Abstract CT 19th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 18-23, 2005 CL Denver, CO SP Associated Profess Sleep Soc C1 VA Greater Los Angeles, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PY 2005 VL 28 SU S MA 47 BP A16 EP A16 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 923JL UT WOS:000228906100049 ER PT J AU Farmer, MM Ferraro, KF AF Farmer, MM Ferraro, KF TI Are racial disparities in health conditional on socioeconomic status? SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE race; socioeconomic status; health; disparities in health; USA ID SAMPLE SELECTION BIAS; QUALITY-OF-LIFE; UNITED-STATES; DOUBLE JEOPARDY; RISK-FACTORS; CONTINUING SIGNIFICANCE; CARDIOVASCULAR-DISEASE; PSYCHOLOGICAL DISTRESS; AFRICAN-AMERICANS; WHITE ADULTS AB Racial health inequality is related to socioeconomic status (SES), but debate ensues on the nature of the relationship. Using the US National Health and Nutrition Examination Survey I and the subsequent follow-up interviews, this research examines health disparities between white and black adults and whether the SES/health gradient differs across the two groups in the USA. Two competing mechanisms for the conditional or interactive relationship between race and SES on health are examined during a 20-year period for black and white Americans. Results show that black adults began the study with more serious illnesses and poorer self-rated health than white adults and that the disparity continued over the 20 years. Significant interactions were found between race and education as well as race and employment status on health outcomes. The interaction effect of race and education showed that the racial disparity in self-rated health was largest at the higher levels of SES, providing some evidence for the "diminishing returns" hypothesis; as education levels increased, black adults did not have the same improvement in self-rated health as white adults. Overall, the findings provide evidence for the continuing significance of both race and SES in determining health status over time. (C) 2004 Elsevier Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D Ctr Excellence, Sepulveda, CA 91343 USA. VA Greater Los Angeles Healthcare Syst, VA Hlth Serv Res & Dev Ctr Excellence, Sepulveda Ambulatory & Nursing Home Ctr, VA Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv,Johnson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90024 USA. Purdue Univ, Dept Sociol, W Lafayette, IN 47907 USA. Purdue Univ, Ctr Aging & Life Course, W Lafayette, IN 47907 USA. RP Farmer, MM (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, HSR&D Ctr Excellence, Bldg 25,Room B110,1611 Plummer St, Sepulveda, CA 91343 USA. EM farmermm@ucla.edu; ferraro@purdue.edu RI Ferraro, Kenneth/E-4811-2011 FU NIA NIH HHS [AG11705] NR 72 TC 177 Z9 179 U1 5 U2 37 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JAN PY 2005 VL 60 IS 1 BP 191 EP 204 DI 10.1016/j.socscimed.2004.04.026 PG 14 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 868XB UT WOS:000224945300017 PM 15482878 ER PT J AU McHale, JP Vinden, PG Bush, L Richer, D Shaw, D Smith, B AF McHale, JP Vinden, PG Bush, L Richer, D Shaw, D Smith, B TI Patterns of personal and social adjustment among sport-involved and noninvolved urban middle-school children SO SOCIOLOGY OF SPORT JOURNAL LA English DT Article ID SELF-ESTEEM; EXTRACURRICULAR ACTIVITIES; DELINQUENT-BEHAVIOR; LEISURE ACTIVITIES; CONDUCT PROBLEMS; SUBSTANCE USE; ADOLESCENTS; PARTICIPATION; AGGRESSION; CHILDHOOD AB This article examines patterns of adjustment among urban middle-school children as a function of involvement in organized team sports. Four hundred twenty-three seventh-grade students (216 boys and 207 girls) reported on their involvement in sport, self-esteem, delinquent activity, and drug use during the year preceding the survey. Physical Education teachers rated social competence, shyness/withdrawal, and disinhibition/aggression. Compared with noninvolved children, sport-involved youth reported higher self-esteem and were rated by teachers as more socially competent and less shy and withdrawn. Sport-involved youth, including those in contact sports, were not rated as more aggressive than noninvolved children. And though sport-involved youth reported a slightly broader range of delinquent activities than noninvolved youth, sport-involved boys were actually less likely than noninvolved boys to have experimented with marijuana. C1 Univ S Florida, Family Study Ctr, St Petersburg, FL 33701 USA. Clark Univ, Frances L Hiatt Sch Psychol, Worcester, MA 01610 USA. Univ Rochester, Rochester, NY 14627 USA. Georgetown Univ, Georgetown Publ Policy Inst, Washington, DC 20057 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Cambridge, MA USA. Tufts Univ, Medford, MA 02155 USA. RP McHale, JP (reprint author), Univ S Florida, Family Study Ctr, St Petersburg, FL 33701 USA. NR 76 TC 31 Z9 31 U1 3 U2 25 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, CHAMPAIGN, IL 61820-2200 USA SN 0741-1235 J9 SOCIOL SPORT J JI Sociol. Sport J. PY 2005 VL 22 IS 2 BP 119 EP 136 PG 18 WC Hospitality, Leisure, Sport & Tourism; Sociology; Sport Sciences SC Social Sciences - Other Topics; Sociology; Sport Sciences GA 940NB UT WOS:000230150100001 ER PT J AU Viktrup, L Koke, S Burgio, KL Ouslander, JG AF Viktrup, L Koke, S Burgio, KL Ouslander, JG TI Stress urinary incontinence in active elderly women SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE elderly; quality of life; stress urinary incontinence; urinary incontinence ID QUALITY-OF-LIFE; COMMUNITY-DWELLING WOMEN; OVERACTIVE BLADDER; POSTMENOPAUSAL WOMEN; UNITED-STATES; DETRUSOR INSTABILITY; EPIDEMIOLOGIC SURVEY; REPLACEMENT THERAPY; PSYCHOSOCIAL IMPACT; URETHRAL PRESSURE AB Urinary incontinence in the elderly is a significant health problem fraught with isolation, depression, and an increased risk of institutionalization and medical complications. Stress urinary incontinence (SUI), the complaint of involuntary loss of urine during effort or exertion or during sneezing or coughing, is the most common type Of urinary incontinence. SUI can seriously degrade the quality of life for many active seniors, and has become an economic challenge for society. With the rapid increase in the active elderly worldwide, SUI is becoming a significant global problem. However, since only a fraction of women with SUI have consulted a physician, the clinical extent and public health impact of SUI are probably underestimated. The Mounting social, medical, and economic problem of SUI in active elderly women as a rapidly growing segment of the population worldwide is reviewed. We evaluate the age-related changes of the lower urinary tract, examine risk factors, and suggest different treatment options shown to be effective in reducing SUI in this population. C1 Emory Univ, Wesley Woods Ctr, Div Geriatr Med & Gerontol, Atlanta, GA 30329 USA. Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Dept Family Med, Bloomington, IN 47405 USA. Univ Alabama, Med Sch Birmingham, Birmingham, AL 35487 USA. Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL 35487 USA. RP Ouslander, JG (reprint author), Emory Univ, Wesley Woods Ctr, Div Geriatr Med & Gerontol, 1841 Clifton Rd NE, Atlanta, GA 30329 USA. EM jouslan@emory.edu NR 123 TC 13 Z9 16 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JAN PY 2005 VL 98 IS 1 BP 79 EP 89 DI 10.1097/01.SMJ.0000146587.06656.98 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 888GA UT WOS:000226361000012 PM 15678640 ER PT B AU Cariani, P AF Cariani, P BE Divenyi, P TI Recurrent timing nets for F0-based speaker separation SO SPEECH SEPARATION BY HUMANS AND MACHINES LA English DT Proceedings Paper CT Workshop on Speech Separation by Humans and Machines CY OCT 31-NOV 02, 2003 CL Montreal, CANADA ID DIFFERENT FUNDAMENTAL FREQUENCIES; AUDITORY-NERVE FIBERS; CONCURRENT VOWELS; TIME; PERCEPTION; RESPONSES; PATTERNS; TONES; PITCH C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Cariani, P (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-8001-8 PY 2005 BP 31 EP 53 DI 10.1007/0-387-22794-6_4 PG 23 WC Computer Science, Artificial Intelligence; Neurosciences; Psychology SC Computer Science; Neurosciences & Neurology; Psychology GA BBH32 UT WOS:000225515900004 ER PT J AU Johansen, KL AF Johansen, KL TI Exercise and chronic kidney disease - Current recommendations SO SPORTS MEDICINE LA English DT Review ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; DIALYSIS PATIENTS; SUBMAXIMAL EXERCISE; CARDIOVASCULAR COMPLICATIONS; MAINTENANCE HEMODIALYSIS; REHABILITATION PROGRAMS; FUNCTIONAL-CAPACITY; TRANSPLANT PATIENTS AB Patients with chronic kidney disease (CKD) are inactive and have reduced physical functioning and performance. Aerobic exercise interventions have been shown to increase maximal oxygen consumption in selected patients. In addition, preliminary evidence, although mixed, suggests that aerobic exercise training can improve blood pressure control, lipid profiles and mental health in this population. A few larger studies are now available showing that aerobic training can also improve physical functioning and performance. The impact on survival or hospitalisation has not been determined. Resistance exercise training, although less studied, appears to increase muscle strength and size and may also improve functioning. There have been several reports of successful combined exercise interventions, but the designs have not allowed evaluation of the relative benefits of aerobic and resistance training on physical functioning. Despite the evidence that exercise is safe and beneficial in patients with CKD, dialysis patients remain inactive, and exercise assessment, counselling and training is not widely offered to patients with CKD. Studies of the barriers to patient participation in exercise and to Provider assessment and recommendations are needed so that more widely generalisable interventions can be developed. However, in the interim, patients should be encouraged to participate in moderate physical activity to meet the US Surgeon General's recommendations. Patients who are weak can benefit from strength-training interventions. Resistance and aerobic exercise programmes should be initiated at relatively low intensity in patients with CKD and progressed as slowly as tolerated in order to avoid injury and discontinuation of exercise. For patients on haemodialysis, incorporation of exercise into the dialysis session may increase patient participation and tolerance of exercise. C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. FU NIDDK NIH HHS [DK-56182] NR 69 TC 48 Z9 55 U1 2 U2 11 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2005 VL 35 IS 6 BP 485 EP 499 DI 10.2165/00007256-200535060-00003 PG 15 WC Sport Sciences SC Sport Sciences GA 945LD UT WOS:000230503100003 PM 15974634 ER PT J AU Lee, MLT Gray, RJ Bjorkbacka, H Freeman, MW AF Lee, MLT Gray, RJ Bjorkbacka, H Freeman, MW TI Generalized rank tests for replicated microarray data SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE rank tests; permutation tests; blocked comparisons ID DIFFERENTIALLY EXPRESSED GENES; FALSE DISCOVERY RATE; STATISTICAL-METHODS; VARIANCE; MODELS; TIES AB Gene expression data from microarray experiments have been studied using several statistical models. Significance Analysis of Microarrays (SAM), for example, has proved to be useful in analyzing microarray data. In the spirit of the SAM procedures, we develop permutation based rank-tests for generalized Wilcoxon ranksum test for two-group comparisons of replicated microarray data. Also, for microarray experiments with randomized block design, we consider generalized signed rank test. The statistical analysis software package is written in R and is freely available in a package. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Lund Univ, Univ Hosp MAS, Wallenberg Lab, Lund, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, MLT (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM meilinglee@sph.osu.edu; gray@jimmy.harvard.edu; harry.bjorkbacka@medforsk.mas.lu.se; freeman@molbio.mgh.harvard.edu NR 25 TC 6 Z9 7 U1 0 U2 0 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MO B JI Stat. Appl. Genet. Mol. Biol. PY 2005 VL 4 AR 3 PG 28 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 055VG UT WOS:000238478100035 ER PT J AU Tsuneto, M Tominaga, A Yamazaki, H Yoshino, M Orkin, SH Hayashi, SI AF Tsuneto, M Tominaga, A Yamazaki, H Yoshino, M Orkin, SH Hayashi, SI TI Enforced expression of PU.1 rescues osteoclastogenesis from embryonic stem cells lacking Tal-1 SO STEM CELLS LA English DT Article DE embryonic stem cells; hematopoiesis; PU.1; transcription factor SCL/Tal-1; osteoclast ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR PU.1; IN-VITRO DIFFERENTIATION; HEMATOPOIETIC LINEAGES; STROMAL CELLS; MICE LACKING; OSTEOPROTEGERIN; PROGENITORS; SCL/TAL-1; LIGAND AB Transcription factor T-cell acute lymphocytic leukemia 1 (Tal-1) is essential for the specification of hematopoietic development. Mice lacking Tal1 fail to generate any hematopoietic precursors. Using our co-culture system with stromal cells, we demonstrate that enforced expression of the transcription factor PU.1 under tetracycline control in Tal1-null embryonic stem (ES) cells rescues the development of osteoclasts and macrophage-like phagocytes. It was low efficiency compared with wild-type ES cells; other hematopoietic lineage cells of granulocytes, B cells, mast cells, megakaryocytes, and erythroid cells were not generated. Osteoclasts developed in this culture were multinucleated and competent for bone resorption. Their development depended on macrophage colony-stimulating factor and receptor activator of nuclear factor kappaB ligand. The majority of cells with the potential to differentiate into osteoclasts expressed fetal liver kinase 1 (Flk-1) and could be isolated using anti-Flk-1 antibody. These results suggest that the expression of PU.1 is a critical event for osteoclastogenesis and that Tal-1 may lie upstream of PU.1 in a regulatory hierarchy during osteoclastogenesis. C1 Tottori Univ, Sch Life Sci, Div Immunol, Dept Mol & Cellular Biol,Fac Med, Yonago, Tottori 6838503, Japan. Grad Sch Kuroshino Sci, Lab Human Hlth & Med Sci, Kochi, Japan. Kochi Med Sch, Dept Mol & Cellular Biol, Kochi, Japan. Tottori Univ, Div Regenerat Med & Therapeut, Dept Genet Med & Regenerat Therapeut, Inst Regenerat Med & Biofunct,Grad Sch Med Sci, Yonago, Tottori, Japan. Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tsuneto, M (reprint author), Tottori Univ, Sch Life Sci, Div Immunol, Dept Mol & Cellular Biol,Fac Med, 86 Nishi Machi, Yonago, Tottori 6838503, Japan. EM tsune13@grape.med.tottori-u.ac.jp NR 31 TC 12 Z9 13 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JAN PY 2005 VL 23 IS 1 BP 134 EP 143 DI 10.1634/stemcells.2004-0154 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 886UY UT WOS:000226259400013 PM 15625130 ER PT J AU Amirnovin, R Neimat, JS Roberts, JA Eskandar, EN AF Amirnovin, R Neimat, JS Roberts, JA Eskandar, EN TI Multimodality treatment of trigeminal neuralgia SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE trigeminal neuralgia; microvascular decompression; percutaneous rhizotomy ID MAGNETIC-RESONANCE ANGIOGRAPHY; MICROVASCULAR DECOMPRESSION; NEUROVASCULAR COMPRESSION; MANAGEMENT; OPERATIONS; PAIN AB Most trigeminal neuralgia (TN) studies focus on a single strategy, microvascular decompression (MVD) or percutaneous rhizotomy (PR). We use a multimodality approach to TN. We perform MVD on patients younger than 70 years and PR on older patients or those where MVD has failed. We performed a chart review of the procedures for TN over the past 3 years and used a questionnaire for long-term follow-up. The questionnaire asked patients to rate their pre- and postoperative pain, outcome, and medication changes. Seventy-four procedures (40 MVDs and 34 PRs) were performed on 67 patients. Twenty patients had undergone previous procedures. 93% of the patients had significant initial pain relief. Over a 1.2-year mean follow-up, 51% of the patients had complete pain relief while 27% had a substantial improvement. There were no deaths and 5 complications. Our results suggest that a multimodality approach to TN yields excellent results with minimal complications. Copyright (C) 2005 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 15 Parkman St,ACC-331, Boston, MA 02114 USA. EM eeskandar@partners.org NR 22 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2005 VL 83 IS 5-6 BP 197 EP 201 DI 10.1159/000091083 PG 5 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 031KX UT WOS:000236704600003 PM 16424684 ER PT J AU Shieh, SJ Vacanti, JP AF Shieh, SJ Vacanti, JP TI State-of-the-art tissue engineering: From tissue engineering to organ building SO SURGERY LA English DT Article ID IN-VITRO; STEM-CELLS; TRANSPLANTATION; INTESTINE; CHANNELS; VIVO C1 Natl Cheng Kung Univ, Coll Med, Div Plast & Reconstruct Surg, Dept Surg, Tainan 70101, Taiwan. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vacanti, JP (reprint author), MassGen Hosp Children, Dept Pediat Surg, 1157 Warren,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 76 Z9 88 U1 1 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2005 VL 137 IS 1 BP 1 EP 7 DI 10.1016/j.surg.2004.04.002 PG 7 WC Surgery SC Surgery GA 883JJ UT WOS:000226007100001 PM 15614274 ER PT J AU Livingston, EH Ko, CY AF Livingston, EH Ko, CY TI Effect of diabetes and hypertension on obesity-related mortality SO SURGERY LA English DT Article ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; CORONARY HEART-DISEASE; NATIONAL-HEALTH; BLOOD-PRESSURE; CARDIOVASCULAR MORTALITY; OLDER PERSONS; UNITED-STATES; 26-YEAR RISK; US ADULTS AB Background. Obesity is increasing and, along with it, greater mortality resulting from the overweight condition. Weight-reduction surgery is recommended for many obese patients based on a perceived risk of greater obesity-related mortality. However, many of the studies cited to justify this have aggregated patient groups together, making it difficult to apply their findings to individual patients. Methods. The,combined National Health Interview Survey database from the years 1986-1994 that has been linked to the National Death Index was analyzed. Patients were stratified for their body mass index (BMI) category, the presence or absence of diabetes and hypertension, gender, and race. The contribution of hypertension and diabetes to mortality was determined by Cox proportional hazards modeling. The absolute magnitude that the effect gender, race, BMI, hypertension, and diabetes had on mortality was determined by examination of stratified age adjusted death rates. Results. We analyzed 662,443 records from individuals interviewed between 1986 and 1994. Of these, 49,391 had died in the follow-up period (mean follow-up, 7.2 years; range, 1-14 years). Cox proportional hazards modeling-adjusting for age, race, and gender-revealed that hypertension (hazard ratio = 1.35 [95 % CI 1.34-1.35], P < .0001) and diabetes (hazard ratio = 2.29 [95 % CI 2.28-2.29], P < .0001) increased mortality independent of body weight. Serious obesity was associated with an increased mortality by Cox modeling (hazard ratio = 1.72 [95 % CI 1.71-1.73], P < .0001); however, when assessed by stratified age-adjusted mortality rates, this increase was numerically small because of the relatively low mortality rate for those without hypertension or diabetes. The presence of hypertension or diabetes substantially increased age-adjusted mortality rates. Much of the increased mortality observed in diabetic patients was attributable to complications of diabetes and not necessarily from atherosclerosis. Conclusion. Because weight-loss surgery successfully cures hypertension or diabetes in most obese patients, it should be considered for obese patients having these diseases. Based on the greatly elevated mortality associated with diabetes, surgery may be justified for obese diabetic patients with BMIs lower than the currently accepted criteria. In contrast, for the morbidly obese without diabetes or hypertension, mortality is only slightly increased from obesity alone. In terms of mortality, the benefits of weight reduction resulting from weight-loss surgery are less clear if there is no coexistent diabetes or hypertension. C1 Univ Texas, SW Med Ctr, SW Med Sch, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. VA N Texas Hlth Care Syst, Dallas, TX USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Livingston, EH (reprint author), Univ Texas, SW Med Ctr, SW Med Sch, Div Gastrointestinal & Endocrine Surg, 5323 Harry Hines Blvd,Room E7-126, Dallas, TX 75390 USA. NR 53 TC 28 Z9 28 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 2005 VL 137 IS 1 BP 16 EP 25 DI 10.1016/j.surg.2004.05.049 PG 10 WC Surgery SC Surgery GA 883JJ UT WOS:000226007100003 PM 15614276 ER PT J AU Wilkinson, HA AF Wilkinson, HA TI Hope, false hope, and self-fulfilling prophecy SO SURGICAL NEUROLOGY LA English DT Editorial Material DE hope; false hope; self-fulfilling prophecy; competent physician; communication skills; motivation AB Hope, false hope, and self-fulfilling prophecy are important aspects in the practice of medicine for all practitioners but are especially important in the field of neurosurgery, which deals with devastating, terrifying, and often fatal illnesses. The American Board of Medical Specialties and the Accreditation Council of Graduate Medical Education have jointly defined 6 "general competencies" that define a competent physician and should be part of the curriculum of all residency programs. One of these 6 is interpersonal and communication skills. A true test of this competence is the ability to harness the powerfully beneficial forces of hope and motivation and to avoid the destructiveness of false hope and self-fulfilling prophecy. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MA Wellesley Hills, MA 02481 USA. RP Wilkinson, HA (reprint author), Massachusetts Gen Hosp, MA Wellesley Hills, MA 02481 USA. EM hrldawlknsn@aol.com NR 4 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JAN PY 2005 VL 63 IS 1 BP 84 EP 86 DI 10.1016/j.surneu.2004.07.048 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 896OU UT WOS:000226944200015 PM 15639539 ER PT S AU Baughman, JM Geijsen, N AF Baughman, JM Geijsen, N BE Hardy, MP Griswold, MD TI In vitro generation of germ cells - New techniques to solve current issues SO TESTICULAR CELL DYNAMICS AND ENDOCRINE SIGNALING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 18th North American Testis Workshop on Testicular Cell Dynamics and Endocrine Signaling CY MAR 30-APR 02, 2005 CL Seattle, WA SP Amer Soc Androl, Amer Soc Reproduct Med, Conrad, Natl Inst Hlth, Serono Reproduct Biol Inst, Wyeth-Ayerst DE primordial germ cells; embryonic stem cells; differentiation; bone morphogenic proteins; germ-line; mammals ID EMBRYONIC STEM-CELLS; MOUSE EMBRYO; SIGNALING PATHWAYS; DIFFERENTIATION; BMP4; SPECIFICATION; POPULATION; DERIVATION; ENDODERM; LINEAGES AB Primordial germ cells comprise a privileged cellular class Within the embryo charged with the elite task of maintaining species longevity. While in lower organisms germ-cell fate is determined by the allocation of germ plasm, mammalian germ-line differentiation requires extracellular signals that converge upon the proximal epiblast. Studies using mutant mice or explanted embryos have identified some of the factors controlling primordial germ-cell specification, such as members of the BMP family, but considerable gaps still exist in our understanding of the complete signaling network. Comprehensive investigations of mammalian germ-line specification have been hampered by the inaccessibility of this cell population in the early embryo. Recently, however, several labs including our own have derived primordial germ cells from embryonic stem cells ill vitro, thus providing a powerful new technique for the study of germ cells. In this review the different methods used for the ill vitro generation of germ cells and how these techniques may be improved and applied to further advance our knowledge of germ-cell biology are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. RP Geijsen, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med & Technol, CPZN 4264,185 Cambridge St, Boston, MA 02114 USA. EM ngeijsen@partners.org NR 38 TC 6 Z9 6 U1 0 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-537-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1061 BP 33 EP 40 DI 10.1196/annals.1336.005 PG 8 WC Andrology; Cell Biology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Endocrinology & Metabolism; Cell Biology; Science & Technology - Other Topics GA BDY46 UT WOS:000236118500004 PM 16467255 ER PT J AU Kushak, RI Nestoridi, E Lambert, J Selig, MK Ingelfinger, JR Grabowski, EF AF Kushak, RI Nestoridi, E Lambert, J Selig, MK Ingelfinger, JR Grabowski, EF TI Detached endothelial cells and microparticles as sources of tissue factor activity SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-04, 2004 CL San Francisco, CA SP Pediat Acad Soc DE endothelial cells; tissue factor (TF); tissue factor pathway inhibitor (TFPI); cell detachment; microparticles ID FACTOR PATHWAY INHIBITOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; MEDITERRANEAN SPOTTED-FEVER; MEMBRANE MICROPARTICLES; MYOCARDIAL-INFARCTION; RICKETTSIA-CONORII; WHOLE-BLOOD; IN-VITRO; PROCOAGULANT; INJURY AB Introduction: Cytokine activation of endothelial cell monolayers is associated with cell detachment, microparticle shedding from plasma membranes, and phosphatidylserine appearance in the plasma membrane outer leaflets. While tissue factor expression on activated endothelial cells and microparticles is well documented, the contribution of detached endothelial cells to tissue factor activity is less clear. We studied tissue factor expression and the rote of tissue factor pathway inhibitor on adherent and detached endothelial cells and on microparticles following endothelial cell activation with TNF-alpha. Materials and methods: Detached endothelial cells and microparticles were obtained from cultures of human umbilical vein endothetial cells by differential centrifugation of cell culture supernatant. For microparticle capture, an antibody directed against CD146 was used. Functional tissue factor activity was measured by chromogenic assay and tissue factor antigen by ELISA. Endothelial cell and microparticle morphology was examined by tight and transmission electron microscopy. Results: After cell activation for 22 h, functional tissue factor activity was distributed as follows: 60%, adherent endothelial cells; 35%, detached cells; and 5%, microparticles. Tissue factor protein followed a similar distribution. Cell detachment was 47%. Electron microscopy demonstrated shedding of microparticles with a diameter of 0. 1-0.6 mu m. Cy3-annexin V revealed increased phosphatidylserine on activated adherent endothelial cells and microparticles. Pre-incubation of adherent and detached endothelial cells and microparticles with anti-tissue factor antibody blocked factor Xa production. Pre-incubation with anti-tissue factor pathway inhibitor antibody increased tissue factor activity of adherent endothetial cells 2.8-fold, detached cells 1.4-fold, and microparticles 45-fold. Conclusions: Detached endothelial cells as well as microparticles from activated endothelial cell monolayers express tissue factor activity, and this activity on microparticles is markedly inhibited by microparticle-associated tissue factor pathway inhibitor. (c) 2005 Published by Elsevier Ltd. C1 Harvard Univ, Sch Med, MassGen Hosp Children, Cardiovasc Thrombosis Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, MassGen Hosp Children, Dept Pathol, Boston, MA 02114 USA. RP Grabowski, EF (reprint author), Harvard Univ, Sch Med, MassGen Hosp Children, Cardiovasc Thrombosis Lab, 55 Fruit St,Jackson 1318, Boston, MA 02114 USA. EM GRABOWSKI.ERIC@MGH.HARVARD.EDU FU NHLBI NIH HHS [HL 33095]; NIDDK NIH HHS [DK 58950] NR 46 TC 33 Z9 35 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 116 IS 5 BP 409 EP 419 DI 10.1016/j.thromres.2005.01.013 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 965ED UT WOS:000231932100006 PM 16122554 ER PT J AU Brent, G Boyle, CA AF Brent, G Boyle, CA TI The impact of maternal thyroid diseases on the developing fetus: Implications for diagnosis, treatment, and screening. Summary of proceedings, workshop organization, program, and participants SO THYROID LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Natl ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA. Univ Calif Los Angeles, Amer Thyroid Assoc, Los Angeles, CA USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Div Thyroid 1, Los Angeles, CA USA. RP Boyle, CA (reprint author), Ctr Dis Control & Prevent, Natl ctr Birth Defects & Dev Disabil, 1600 Clifton Rd,Mailstop E-87, Atlanta, GA 30333 USA. EM cboyle@cdc.gov NR 5 TC 2 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 2005 VL 15 IS 1 BP 36 EP 40 DI 10.1089/thy.2005.15.36 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 896FX UT WOS:000226921100007 PM 15687821 ER PT J AU Smallridge, RC Glinoer, D Hollowell, JG Brent, G AF Smallridge, RC Glinoer, D Hollowell, JG Brent, G TI Thyroid function inside and outside of pregnancy: What do we know and what don't we know? SO THYROID LA English DT Article; Proceedings Paper CT Workshop on the Impact of Maternal Thyroid Diseases on the Developing Fetus CY JAN 12-13, 2004 CL Atlanta, GA ID IODINE DEFICIENCY; POSTPARTUM THYROIDITIS; PEROXIDASE ANTIBODIES; DIABETES-MELLITUS; DYSFUNCTION; WOMEN; AUTOANTIBODIES; HYPOTHYROIDISM; REPERCUSSIONS; DEPRESSION AB A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the session that examined the prevalence of thyroid dysfunction in reproductive-age women and the factors associated with abnormal function. For this session the following papers were presented: "Thyroidal Economy in the Pregnant State: An Overview," "The Prevalence of Thyroid Dysfunction in Reproductive-Age Women-United States," and "Risk Factors for Thyroid Disease: Autoimmunity and Other Conditions." These presentations were formally discussed by invited respondents and by others in attendance. Salient points from this session about which there was agreement include the following: physiologic changes associated with pregnancy require an increased availability of thyroid hormones by 40% to 100% in order to meet the needs of mother and fetus during pregnancy. In the first trimester of gestation the fetus is wholly dependent on thyroxine from the mother for normal neurologic development. For the maternal thyroid gland to meet the demands of pregnancy it must be present, disease-free, and capable of responding with adequate stores of iodine. Thyroid autoimmunity is common and may contribute to miscarriages, as well as to hypothyroidism. With sufficient iodine nutrition, autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism. As of 1994, iodine nutrition in the United States appeared to be adequate, but its continued monitoring is essential. C1 Univ Kansas, Med Ctr, Lawrence, KS 66049 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Free Univ Brussels, Hop Univ St Pierre, Thyroid Invest Clin, Brussels, Belgium. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Amer Thyroid Assoc, Los Angeles, CA USA. RP Hollowell, JG (reprint author), Univ Kansas, Med Ctr, 435 N 1400 Rd, Lawrence, KS 66049 USA. EM jgh3@mindspring.com NR 43 TC 37 Z9 42 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 2005 VL 15 IS 1 BP 54 EP 59 DI 10.1089/thy.2005.15.54 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 896FX UT WOS:000226921100010 PM 15687824 ER PT J AU Jayaraman, A Yarmush, ML Roth, CM AF Jayaraman, A Yarmush, ML Roth, CM TI Evaluation of an in vitro model of hepatic inflammatory response by gene expression profiling SO TISSUE ENGINEERING LA English DT Article ID ACUTE-PHASE RESPONSE; BURN INJURY; SANDWICH CONFIGURATION; OXIDATIVE STRESS; RAT HEPATOCYTES; PLASMA-PROTEINS; NUCLEAR FACTOR; ACTIVATION; LIVER; INTERLEUKIN-6 AB The body's response to biochemical stress involves coordinated changes in the expression of several sets of genes that regulate its return to homeostasis. Although several cell culture systems have been utilized for studying such complex physiological events in vitro, their assessment has been limited to biochemical assays on individual genes and proteins, limiting interpretation of the results in a systems context. Advances in genomics provide an opportunity to provide a more comprehensive assessment. In this study, we have used DNA microarrays to profile gene expression dynamics during interleukin 6-stimulated inflammation in hepatocytes maintained in a stable, collagen doublegel in vitro model system. The observed expression profile was also compared with that obtained from rat liver tissue after burn injury to determine the extent and nature of responses captured by the in vitro system. Our results indicate that several aspects of the in vivo hepatic inflammatory response can be captured by the in vitro system at the molecular systems level. Statistical analysis of the mRNA profiles was also used to characterize the temporal response in each model system and demonstrate similar behavior. A small panel of molecules involved in the hepatic acute-phase response was also profiled, using quantitative kinetic polymerase chain reaction, to confirm these observations. These results indicate the utility of the stable hepatocyte culture system for expression profiling of inflammatory states and for providing insights into the interplay of changes in gene expression during complex physiological states. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA. Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ USA. RP Yarmush, ML (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org OI Roth, Charles/0000-0002-4924-0721 FU NIGMS NIH HHS [5R01-GM-65474] NR 49 TC 16 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN PY 2005 VL 11 IS 1-2 BP 50 EP 63 DI 10.1089/ten.2005.11.50 PG 14 WC Cell & Tissue Engineering SC Cell Biology GA 904QU UT WOS:000227513600005 PM 15738661 ER PT J AU Rotter, N Ung, F Roy, AK Vacanti, M Eavey, RD Vacanti, CA Bonassar, LJ AF Rotter, N Ung, F Roy, AK Vacanti, M Eavey, RD Vacanti, CA Bonassar, LJ TI Role for interleukin 1 alpha in the inhibition of chondrogenesis in autologous implants using polyglycolic acid-polylactic acid scaffolds SO TISSUE ENGINEERING LA English DT Article ID HUMAN SEPTAL CARTILAGE; ARTICULAR-CARTILAGE; PHYSICAL-PROPERTIES; NASAL CHONDROCYTES; POLYMER SCAFFOLDS; AGE-DEPENDENCE; TISSUE; RECONSTRUCTION; DEGRADATION; EXPRESSION AB Significant challenges remain in generating tissue-engineered cartilage in immunocompetent animals. Scaffold materials such as polyglycolic acid lead to significant inflammatory reactions, inhibiting homogeneous matrix synthesis. This study examined the generation of tissue-engineered cartilage, using a polyglycolic acid - polylactic acid copolymer (Ethisorb; Ethicon, Norderstedt, Germany) in an autologous immunocompetent pig model. The goals of this study were to determine the role of interleukin 1 alpha (IL-1 alpha) in this system and to assess the effect of serum treatment on tissue generation. Porcine auricular chondrocytes were seeded onto Ethisorb disks cultured for 1 week in medium supplemented with either fetal bovine serum or serum-free insulin - transferrin - selenium supplement. Specimens were implanted autogenously in pigs with unseeded scaffolds as controls. After 1, 4, or 8 weeks, six specimens from each group were explanted and analyzed histologically ( hematoxylin and eosin, safranin O, trichrome, and Verhoeff's staining) and biochemically ( glycosaminoglycan content). The presence and distribution of IL-1 alpha were assessed by immunohistochemistry. Histology revealed acute inflammation surrounding degrading scaffold. Cartilage formation was observed as early as 1 week after implantation and continued to increase with time; however, homogeneous matrix synthesis was not present in any of the specimens. Strong IL-1 alpha expression was detected in chondrocytes at the implant periphery and in cells in the vicinity of degrading polymer. Histologically there was no significant difference between the experimental groups with respect to the amount of matrix synthesis or inflammatory infiltration. The glycosaminoglycan content was significantly higher in the serum-free group. These results suggest that inflammatory reactions against scaffold materials and serum components lead to the production of cytokines such as IL-1 alpha that may inhibit cartilage tissue formation in autologous transplant models. C1 Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. Univ Massachusetts, Med Ctr, Ctr Tissue Engn, Worcester, MA USA. Univ Hosp Schleswig Holstein, Dept Otorhinolaryngol Head & Neck Surg, D-23538 Lubeck, Germany. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA. RP Bonassar, LJ (reprint author), Cornell Univ, Sibley Sch Mech & Aerosp Engn, 218 Upson Hall, Ithaca, NY 14853 USA. EM nicole.rotter@hno.uni-luebeck.de; LB244@cornell.edu RI Bonassar, Lawrence/C-2103-2016; OI Bonassar, Lawrence/0000-0003-1094-6433; Rotter, Nicole/0000-0003-1537-8340 NR 26 TC 35 Z9 41 U1 3 U2 8 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 JAN PY 2005 VL 11 IS 1-2 BP 192 EP 200 DI 10.1089/ten.2005.11.192 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 904QU UT WOS:000227513600018 PM 15738674 ER PT J AU Fidkowski, C Kaazempur-Mofrad, MR Borenstein, J Vacanti, JP Langer, R Wang, YD AF Fidkowski, C Kaazempur-Mofrad, MR Borenstein, J Vacanti, JP Langer, R Wang, YD TI Endothelialized microvasculature based on a biodegradable elastomer SO TISSUE ENGINEERING LA English DT Article ID TISSUE; POLY(DIMETHYLSILOXANE); CHANNELS AB Vital organs maintain dense microvasculature to sustain the proper function of their cells. For tissue-engineered organs to function properly, artificial capillary networks must be developed. We have microfabricated capillary networks with a biodegradable and biocompatible elastomer, poly( glycerol sebacate) ( PGS). We etched capillary patterns onto silicon wafers by standard microelectromechanical systems (MEMS) techniques. The resultant silicon wafers served as micromolds for the devices. We bond the patterned PGS film with a flat film to create capillary networks that were perfused with a syringe pump at a physiological flow rate. The devices were endothelialized under flow conditions, and part of the lumens reached confluence within 14 days of culture. This approach may lead to tissue-engineered microvasculature that is critical in vital organs engineering. C1 Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Dept Mech & Biol Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. Georgia Inst Technol, Sch Chem & Biochem, Atlanta, GA 30332 USA. RP Wang, YD (reprint author), Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. EM rlanger@mit.edu; yadong.wang@bme.gatech.edu OI Wang, Yadong/0000-0003-2067-382X FU NHLBI NIH HHS [HL-60435] NR 16 TC 215 Z9 222 U1 5 U2 48 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN PY 2005 VL 11 IS 1-2 BP 302 EP 309 DI 10.1089/ten.2005.11.302 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 904QU UT WOS:000227513600028 PM 15738683 ER PT J AU Saito, Y Dzik, S AF Saito, Y Dzik, S TI Gene knockdown: RNA-interference is coming of age SO TRANSFUSION LA English DT Article ID MESSENGER C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, S (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St,J-224, Boston, MA 02114 USA. EM sdzik@partners.org NR 8 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2005 VL 45 IS 1 BP 111 EP 114 DI 10.1111/j.1537-2995.2005.04282.x PG 4 WC Hematology SC Hematology GA 882JG UT WOS:000225934600018 PM 15647026 ER PT J AU Uehara, S Chase, CM Colvin, RB Russell, PS Madsen, JC AF Uehara, S Chase, CM Colvin, RB Russell, PS Madsen, JC TI Further evidence that NK cells may contribute to the development of cardiac allograft vasculopathy SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 20th International Congress of the Transplantation-Society CY SEP 05-10, 2004 CL Vienna, AUSTRIA SP Transplantat Soc ID TRANSPLANTED MOUSE HEARTS; CORONARY ATHEROSCLEROSIS; IMMUNITY AB In prior experiments, we found that recipients, even though specifically tolerant of donor antigens, will develop striking cardiac allograft vasculopathy (CAV) in allogeneic mouse heart transplants. This suggested that innate immune responses, in addition to conventional adaptive immunity, may be involved in the development of CAV. We accordingly performed transplants in the parental-to-F1 combination seeking supportive evidence of NK cell activity directed against the vessels of parental donor transplants as a manifestation of "hybrid resistance." When such lesions were indeed found, we investigated their pathogenesis employing immunopathological analysis, in vitro measurements of NK cytotoxicity, and donor-specific T-cell activity in F1 recipients of parental donor hearts. We present evidence that NK cells can promote cardiac allograft vasculopathy. Since NK cell activity is not well targeted by current immunosuppressive therapy, its control may offer a valuable new possibility for improving the long-term outcome of transplanted organs. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Cardiac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Div, Fruit St,EDR 105, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu NR 6 TC 14 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2005 VL 37 IS 1 BP 70 EP 71 DI 10.1016/j.transproceed.2005.01.052 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 912PJ UT WOS:000228091300026 PM 15808550 ER PT J AU Shoji, T Muniappan, A Guenther, DA Wain, JC Houser, SL Hoerbelt, R Benjamin, LC Hasse, RS Bravard, MA Sachs, DH Madsen, JC Allan, JS AF Shoji, T Muniappan, A Guenther, DA Wain, JC Houser, SL Hoerbelt, R Benjamin, LC Hasse, RS Bravard, MA Sachs, DH Madsen, JC Allan, JS TI Long-term acceptance of porcine pulmonary allografts without chronic rejection SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 20th International Congress of the Transplantation-Society CY SEP 05-10, 2004 CL Vienna, AUSTRIA SP Transplantat Soc ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; TRANSPLANTATION; LUNG AB Objectives. The mechanisms and treatment of chronic rejection in pulmonary allotransplantation remain elusive. Using a strategy to induce tolerance across strong allogeneic barriers, we have employed a brief, intensive course of immunosuppression to determine whether the induction of donor-specific hyporesponsiveness would prevent allograft rejection in a preclinical model of lung transplantation using MHC-inbred miniature swine. Methods. Orthotopic left lung allografts were performed using MHC class I-disparate donors. The recipients received a 12-day postoperative course of cyclosporine (n = 6) or a 12-day postoperative course of high-dose tacrolimus (n = 3) as their only immunosuppression. Control animals received no immunosuppression (n = 3). Results. Cyclosporine-treated recipients exhibited graft survival ranging from 67 to > 605 days. All six animals developed acute cellular rejection between postoperative days (PODs) 27 and 108. Two animals lost their grafts on PODS 67 and 69, before developing obliterative bronchiolitis (OB). The other four recipients developed OB between PODs 119 and 238. In contrast, all tacrolimus-treated recipients maintained their grafts long term, without developing chronic rejection (> 339, > 308, and > 231). These recipients also exhibited donor-specific hyporesponsiveness in assays of cell-mediated lymphocytotoxity. All untreated control animals lost their grafts to acute rejection by POD 11. Conclusions. This study demonstrates the ability of a brief course of high-dose tacrolimus to induce long-term graft acceptance with donor-specific hyporesponsiveness in a class I-disparate preclinical lung transplant model. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM jallan@partners.org FU NHLBI NIH HHS [R01-HL67110-01]; NIAID NIH HHS [P01-AI50157] NR 5 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2005 VL 37 IS 1 BP 72 EP 74 DI 10.1016/j.transproceed.2004.12.026 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 912PJ UT WOS:000228091300027 PM 15808551 ER PT J AU Dor, FJMF Kuwaki, K Tseng, YL Shimizu, A Houser, SL Yamada, K Hawley, RJ Patience, C Awwad, M Fishman, JA Robson, SC Sachs, DH Schuurman, HJ Cooper, DKC AF Dor, FJMF Kuwaki, K Tseng, YL Shimizu, A Houser, SL Yamada, K Hawley, RJ Patience, C Awwad, M Fishman, JA Robson, SC Sachs, DH Schuurman, HJ Cooper, DKC TI Potential of aspirin to inhibit thrombotic microangiopathy in alpha 1,3-galactosyltransferase gene-knockout pig hearts after transplantation in baboons SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 20th International Congress of the Transplantation-Society CY SEP 05-10, 2004 CL Vienna, AUSTRIA SP Transplantat Soc AB Hearts from alpha 1,3-Galactosyltransferase gene-knockout (GaIT-KO) pigs were transplanted heterotopically into 8 baboons that received an anti-CD154 monoclonal antibody (mAb)-based immunosuppressive regimen and heparin. Three baboons died or were euthanized with beating grafts on 16, 23, and 56 days, respectively, and the remaining 5 grafts functioned for 59-179 days. Hyperacute rejection did not occur, and classical features of acute humoral xenograft or acute cellular rejection were rare. However, thrombotic microangiopathy (TM) developed in all cases; its onset was delayed in 2 baboons that received aspirin. Function of a pig organ in a baboon for a period approaching 6 months has not been reported previously and lends encouragement that the barriers to xenotransplantation will be overcome, but TM requires investigation. C1 Massachusetts Gen Hosp, Ctr Immunobiol, Transplant Biol Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunobiol, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Immunobiol, Div Infect Dis, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Immerge BioTherapeut Inc, Boston, MA USA. RP Dor, FJMF (reprint author), Erasmus MC, Dr Molewaterpl 40,POB 2040, NL-3000 CA Rotterdam, Zuid Holland, Netherlands. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 NR 5 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD JAN-FEB PY 2005 VL 37 IS 1 BP 489 EP 490 DI 10.1016/j.transproceed.2004.12.235 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 912PJ UT WOS:000228091300161 PM 15808685 ER PT J AU Schroeder, C Allan, JS Nguyen, BN Wu, G Zhang, T Azimzadeh, AM Madsen, JC Schuurman, HJ Sachs, DH Pierson, RN AF Schroeder, C Allan, JS Nguyen, BN Wu, G Zhang, T Azimzadeh, AM Madsen, JC Schuurman, HJ Sachs, DH Pierson, RN TI Hyperacute rejection is attenuated in GaIT knockout swine lungs perfused ex vivo with human blood SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 20th International Congress of the Transplantion-Society CY SEP 05-10, 2004 CL Vienna, AUSTRIA SP Transplant Soc ID COMPLEMENT; MODEL AB Background. Hyperacute rejection (HAR) is one of the principal obstacles to successful xenotransplantation. Homozygous alpha-1,3-galactosyltransferase knockout (GalT-KO) miniature swine now offer the prospect of overcoming this barrier to xenotransplantation. In this study, the short-term function of GalT-KO swine lungs was evaluated in a well-established ex vivo model of swine-to-human lung xenotransplantation. Methods. Lungs from homozygous GalT-KO swine (n = 3) and control lungs from pigs of the background strain used to create the GalT-KO pig line (n = 2) were perfused ex vivo with freshly collected heparinized human blood. Graft function was assessed by various physiologic measurements, serial histologic and immunohistochemical evaluation, and assays of complement and platelet activation. Results. Xenoperfused control swine lungs exhibited HAR with graft survival times < 5 minutes. In contrast, GalT-KO swine lungs retained their function for approximately 2 hours, on average. GaIT-KO swine lungs showed decreased complement and platelet activation compared with controls. Nonetheless, activation of complement and coagulation cascades was not completely eliminated in the GaIT-KO swine lungs. Conclusions. The survival of xenoperfused GalT-KO swine lungs was significantly prolonged, as compared with control lungs expressing Gal. This appears to have been due largely to substantially reduced complement activation. Nonetheless, the xenoperfused GalT-KO lungs still showed some evidence of complement fixation and intravascular coagulopathy by the time of graft demise. C1 Harvard Univ, Sch Med, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Allan, JS (reprint author), Harvard Univ, Sch Med, Dept Surg, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM jallan@partners.org NR 5 TC 24 Z9 25 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JAN-FEB PY 2005 VL 37 IS 1 BP 512 EP 513 DI 10.1016/j.transproceed.2004.12.133 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 912PJ UT WOS:000228091300169 PM 15808693 ER PT S AU Hartman, AR AF Hartman, AR BE Senn, HJ Morant, R TI The problems with risk selection; Scientific and psychosocial aspects SO TUMOR PREVENTION AND GENETICS III SE Recent Results in Cancer Research LA English DT Proceedings Paper CT Pediatric Psycho-Oncology Research Summit CY OCT, 2001 CL San Antonio, TX SP Childhood Canc Grp, NCI ID FINE-NEEDLE-ASPIRATION; BREAST-CANCER RISK; HIGH GENETIC RISK; OVARIAN-CANCER; FAMILY-HISTORY; PROPHYLACTIC MASTECTOMY; SEQUENCE-ANALYSIS; BRCA2 MUTATION; WOMEN; MAMMOGRAPHY AB Between 9,000 and 18,000 new cases of breast cancer per year in the United States are associated with a genetically defined predisposition [ 1, 2]. Mutations in BRCA1 and 2 account for greater than 60% of inherited breast cancer. Mutations in additional undiscovered high and low penetrance genes may account for the other 40% of inherited breast cancer cases and possibly a subset of familial breast cancer cases that lacks an autosomal-dominant pattern of inheritance. False-negative rates resulting from gene sequencing of BRCA1 and 2 may be as high as 10%-15%, making the identification of high-risk individuals a complex and often futile process for both patient and physician. As a consequence of technical limitations in BRCA1 and 2, genetic testing and the lack of comprehensive breast cancer prediction models that take into account both genetic and environmental factors, we are unable to quantify future breast cancer risk for many patients. This uncertainty often leads to the exclusion of high-risk individuals in screening and prevention trials, which is perhaps most evident in breast cancer screening trials incorporating the use of magnetic resonance imaging (MRI) to identify early cancers [3-10]. These studies demonstrate that MRI increases the sensitivity of a screening protocol in mutation carriers and succeeds at detecting earlier stage cancers [3-10]. Eligibility criterion for most of these trials was documented mutations in BRCA1 and 2 or future breast cancer risk predicted by family history or models, thereby possibly excluding women at significantly elevated risk that testing failed to identify or whose risk is not adequately reflected based on current models used in risk assessment. We may be turning very high-risk women away from screening trials, recommending yearly mammography and clinical breast exam, when neither will be adequate for detecting their cancers early. In addition, the impact of risk-reducing strategies including bilateral prophylactic oophorectomy (BSO) and tamoxifen has not been analyzed in these studies. For example, a 40-year-old BRCA2 carrier may only have a 10% and 50% lifetime risk of ovarian and breast cancer, respectively, and interventions including tamoxifen and breast MRI screening may significantly reduce the risk of both getting breast cancer and dying from it, thereby obviating the need for early screening or prophylactic surgeries, permitting these women to defer the quality of life struggles until they are older. A larger sample size is needed to determine the degree to which different subgroups of high-risk patients will benefit from MRI screening, with particular attention to women who have undergone BSO or who are taking tamoxifen. The challenges in risk selection are numerous and produce more questions than answers with regard to screening and management of high-risk individuals. In the future, we hope that early detection tools, risk-reduction strategies, and risk assessment preclude the need for prophylactic surgeries, inappropriate selection of patients for screening, and the associated decisions that compromise our patients' quality of life. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hartman, AR (reprint author), Dana Farber Canc Inst, 44 Binney St,SM 203, Boston, MA 02115 USA. EM anne-renee_hartman@dfci.harvard.edu NR 42 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-22228-6 J9 RECENT RES CANCER PY 2005 VL 166 BP 125 EP 144 PG 20 WC Oncology SC Oncology GA BBN83 UT WOS:000226377400010 PM 15648188 ER PT S AU Zhang, GJ Kaelin, WG AF Zhang, GJ Kaelin, WG BE Deshaies, RJ TI Bioluminescent imaging of ubiquitin ligase activity: Measuring cdk2 activity in vivo through changes in p27 turnover SO UBIQUITIN AND PROTEIN DEGRADATION, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID DEPENDENT PROTEIN-KINASE; FIREFLY LUCIFERASE; PHOSPHORYLATION; DEGRADATION; INHIBITION; INDICATOR; P27(KIP1); COMPLEX; CELLS AB Optical imaging of reporter molecules such as firefly luciferase has become a popular method of tracking and visualizing cells in living animals. Many biological processes involve ubiquitin ligases, which target specific proteins for destruction under specific sets of conditions. Importantly, the motifs recognized by different ubiquitin ligases are often modular and can be used to target foreign proteins for destruction in cis. We recently fused the Cdk inhibitor p27, which is polyubiquitylated by a Skp2-containing ubiquitin ligase if phosphorylated by cdk2 to firefly luciferase. The resulting fusion protein, p27-Luc, was induced by cdk2 inhibitors in living cells grown in culture or in nude mice. This article describes protocols for validation of p27-Luc in cell culture using siRNA against cdk2 (or its partner cyclin A) and for imaging cells producing p27-Luc grown in transparent hollow fibers after treatment with cdk2 inhibitory drugs in vivo. These approaches should be generalizable to other ubiquitin-ligase substrate pairs. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhang, GJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Zhang, Guo-Jun/H-3890-2015 OI Zhang, Guo-Jun/0000-0001-5182-5887 NR 15 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182804-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 399 BP 530 EP + DI 10.1016/S0076-6879(05)99036-8 PN B PG 22 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDI27 UT WOS:000233597300036 PM 16338380 ER PT J AU Rosenfield, K Babb, JD Cates, CU Cowley, MJ Feldman, T Gallagher, A Gray, W Green, R Jaff, MR Kent, KC Ouriel, K Roubin, GS Weiner, BH White, CJ AF Rosenfield, K Babb, JD Cates, CU Cowley, MJ Feldman, T Gallagher, A Gray, W Green, R Jaff, MR Kent, KC Ouriel, K Roubin, GS Weiner, BH White, CJ TI SCAI/SVMB/SVS Clinical Competence Statement on carotid stenting: training and credentialing for carotid stenting - multispecialty consensus recommendations - A report of the SCAI/SVMB/SVS Writing Committee to develop a clinical competence statement on carotid interventions SO VASCULAR MEDICINE LA English DT Article ID ARTERIES; DISEASE C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Rosenfield, K (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bullfinch 105, Boston, MA 02114 USA. EM krosenfield@fastmail.us NR 7 TC 8 Z9 8 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2005 VL 10 IS 1 BP 65 EP 75 DI 10.1191/1358863x05vm583xx PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 922HR UT WOS:000228828200013 ER PT J AU Musicant, SE Roullet, JB Edwards, JM Moneta, GL AF Musicant, Scott E. Roullet, Jean-Baptiste Edwards, James M. Moneta, Gregory L. BE White, RA Hollier, LH TI Physiology of vasospastic disorders SO VASCULAR SURGERY: BASIC SCIENCE AND CLINICAL CORRELATIONS, 2ND EDITION LA English DT Article; Book Chapter ID GENE-RELATED PEPTIDE; PRIMARY RAYNAUDS-PHENOMENON; HUMAN SAPHENOUS-VEIN; SERUM ENDOTHELIN-1 CONCENTRATIONS; COLD-INDUCED VASOCONSTRICTION; CORONARY ARTERIAL SPASM; HUMAN DIGITAL ARTERIES; SMOOTH-MUSCLE; ADRENERGIC-RECEPTORS; ALPHA-ADRENOCEPTORS C1 [Musicant, Scott E.; Roullet, Jean-Baptiste; Edwards, James M.; Moneta, Gregory L.] Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97201 USA. [Edwards, James M.] Portland VA Med Ctr, Portland, OR USA. RP Musicant, SE (reprint author), Oregon Hlth & Sci Univ, Div Vasc Surg, Portland, OR 97201 USA. NR 145 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98709-4 PY 2005 BP 80 EP 91 DI 10.1002/9780470987094.ch7 D2 10.1002/9780470987094 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA BYD13 UT WOS:000298080000008 ER PT B AU Servoss, JC Friedman, LS Dienstag, JL AF Servoss, Julie C. Friedman, Lawrence S. Dienstag, Jules L. BE Thomas, H Lemon, S Zuckerman, A TI Diagnostic approach to viral hepatitis SO VIRAL HEPATITIS, 3RD EDITION LA English DT Article; Book Chapter ID NON-B-HEPATITIS; TO-INFANT TRANSMISSION; CHRONIC ACTIVE HEPATITIS; DELTA-VIRUS INFECTION; C VIRUS; NON-A; CORE ANTIGEN; HEPATOCELLULAR-CARCINOMA; INTERNATIONAL STANDARD; CLINICAL-EVALUATION C1 [Servoss, Julie C.; Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA 02462 USA. RP Servoss, JC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98713-1; 978-1-4051-3005-9 PY 2005 BP 50 EP 64 DI 10.1002/9780470987131.ch4 D2 10.1002/9780470987131 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZS84 UT WOS:000302866100005 ER PT J AU Imber, ML Shapley, RM Rubin, N AF Imber, ML Shapley, RM Rubin, N TI Differences in real and illusory shape perception revealed by backward masking SO VISION RESEARCH LA English DT Article DE illusory contours; boundary interpolation; real contours; size invariance; shape discrimination ID LATERAL OCCIPITAL COMPLEX; OBJECT-RECOGNITION AREAS; MASKED INDUCING FIGURE; SUBJECTIVE CONTOURS; VISUAL-CORTEX; ACTIVATION; REPRESENTATION; ILLUSION; INTERPOLATION; MICROGENESIS AB Illusory contours (ICs) are thought to be a result of processes involved in the perceptual recovery of occluded surfaces. Here, we investigate the relationship between real and illusory contour perception using a shape discrimination task and backward masking paradigm. lCs can mask other ICs when times between mask onset and stimulus onset, or SOAs, are very long (similar to 300ms), but real contours (RCs) are not similarly effective. Masking is absent for RC masks at perceptually salient contrasts, as well as for those with contrast lowered to match the perceived brightness of the illusory surface. We also find that RCs are not masked at long SOAs, either by ICs or by other RCs. Finally, the masking seen between ICs can occur for different sizes of target and mask. The cross-size masking would not be expected if the masking were at a level sensitive to retinal contour location. The late masking therefore may be related to a higher level of processing of shape categories and surfaces, the level at which shapes defined by ICs and RCs are differentially represented. (c) 2004 Elsevier Ltd. All rights reserved. C1 NYU, Dept Psychol, New York, NY 10003 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Imber, ML (reprint author), Brigham & Womens Hosp, Brigham Behav Neurol Grp, 221 Longwood Ave,M Level, Boston, MA 02115 USA. EM michelle_imber@hms.harvard.edu RI Rubin, Nava/J-5189-2012 FU NEI NIH HHS [R01 EY-01472] NR 61 TC 14 Z9 16 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PY 2005 VL 45 IS 1 BP 91 EP 102 DI 10.1016/j.visres.2004.07.034 PG 12 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 908DH UT WOS:000227767000008 PM 15571740 ER PT J AU Demay, MB AF Demay, Marie B. BE Feldman, D TI Mouse Models of Vitamin D Receptor Ablation SO VITAMIN D: VOLS 1 AND 2, 2ND EDITION LA English DT Article; Book Chapter ID DUODENAL CALCIUM-ABSORPTION; MINERAL ION HOMEOSTASIS; KNOCKOUT MICE; PHOSPHATE IONS; NULL MICE; EPIDERMAL DIFFERENTIATION; MUTANT MICE; EXPRESSION; APOPTOSIS; ALOPECIA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit,Dept Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit,Dept Med, Boston, MA 02114 USA. NR 36 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-252687-9 PY 2005 BP 341 EP 349 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BCV82 UT WOS:000311626800022 ER PT S AU Filley, CM AF Filley, CM BE Ulmer, JL Parsons, L Moseley, M Gabrieli, J TI White matter and behavioral neurology SO WHITE MATTER IN COGNITIVE NEUROSCIENCE: ADVANCES IN DIFFUSION TENSOR IMAGING AND ITS APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Workshop on White Matter in the Cognitive Neurosciences CY AUG 19-20, 2004 CL New York Acad Sci, New York, NY SP Gen Elect Hlth Care Syst, Mushett Family Fdn, Natl Inst Hlth, Natl Sci Fdn, New York Acad Sci, Siemens Med HO New York Acad Sci DE white matter; behavioral neurology; magnetic resonance imaging; dementia; diffusion tensor imaging ID MILD COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS; DISEASE; DEMENTIA; EVOLUTION; BRAIN; MRI; LEUKOENCEPHALOPATHY; DYSFUNCTION AB Although the study of higher brain function has traditionally focused on the cortical gray matter, recent years have witnessed the recognition that white matter also makes an important contribution to cognition and emotion. White matter comprises nearly half the brain volume and plays a key role in development, aging, and many neurologic and psychiatric disorders across the life span. More than 100 disorders exist in which white matter neuropathology is the primary or a prominent feature. A variety of neurobehavioral syndromes may result from these disorders; the concept of white matter dementia has been introduced as characteristic of many patients with white matter involvement, and a wide range of focal neurobehavioral syndromes and psychiatric disorders can also be related to dysfunction of myelinated tracts. Understanding the neurobehavioral aspects of white matter disorders is important for clinical diagnosis, treatment, prognosis, and research on brain-behavior relationships. Central to these investigations is the use of modern neuroimaging techniques, which have already provided substantial information on the characterization of white matter and its disorders, and which promise to advance our knowledge further with continued innovation. Diffusion tensor imaging is an exciting method that will assist with the identification of critical white matter tracts in the brain, and the localization of specific lesions that can be correlated with neurobehavioral syndromes. A behavioral neurology of white matter is thus emerging in which clinical observation combined with sophisticated neuroimaging will enable elucidation of the role of white matter connectivity in the distributed neural networks subserving higher brain function. C1 Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), Univ Colorado, Hlth Sci Ctr, Behav Neurol Sect, 4200 E 9th Ave, Denver, CO 80262 USA. EM christopher.filley@uchsc.edu NR 67 TC 40 Z9 42 U1 2 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-545-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1064 BP 162 EP + DI 10.1196/annals.1340.028 PG 23 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Neuroimaging SC Science & Technology - Other Topics; Neurosciences & Neurology GA BDU41 UT WOS:000235430200012 PM 16394155 ER PT J AU Steele, WR Mebane, F AF Steele, WR Mebane, F TI News media coverage of a women's health controversy: How newspapers and TV outlets covered a recent debate over screening mammography SO WOMEN & HEALTH LA English DT Article DE mammography; mass media; news coverage; breast neoplasms; prevention and control ID BREAST-CANCER AB Over the past decade, there have been several highly visible debates about mammography that have captured professional, public, and media attention. This paper looks at newspaper and television news coverage of a controversial research letter in The Lancet by Gotzsche and Olsen (2001) that concluded that screening mammography did not prevent deaths from breast cancer. The news pieces examined for this project were published between October 2001 and March 2002 in one of eight U.S. newspapers or aired on one of six national or cable news networks. The six-month period was divided into one-week segments; the numbers of articles published or stories aired in each week were graphed to examine patterns. Each newspaper article and television transcript was then reviewed to identify its main content area and the amount of coverage for each major event was quantified. The highest number of newspaper articles appeared to result from several events during the end of January through the beginning of February. These events included the publication of another meta-analysis of mammography that disputed the original letter's conclusion and a full-page New York Times advertisement paid for by major medical organizations stating their continued support for mammography. The greatest amount of television news coverace was devoted to the announcement of the official federal guidelines by the Secretary of Health and Human Services in late February. We conclude by discussing how the flow of news coverage of medical controversies can potentially impact the actions and reactions of the public, the medical community, and health policy makers. C1 Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Steele, WR (reprint author), 1650 Res Blvd,TB164, Rockville, MD 20850 USA. EM whitneysteele@gmail.com NR 25 TC 15 Z9 15 U1 2 U2 9 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2005 VL 41 IS 3 BP 83 EP 97 DI 10.1300/J013v41n03_05 PG 15 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 999DO UT WOS:000234369100005 PM 15970577 ER PT J AU Hess, R Chang, CCJ Conigliaro, J McNeil, M AF Hess, R Chang, CCJ Conigliaro, J McNeil, M TI Understanding physicians' attitudes towards hormone therapy SO WOMENS HEALTH ISSUES LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the North-American-Menopause-Society CY SEP 17-20, 2003 CL Miami Beach, FL SP N Amer Menopause Soc ID ESTROGEN-REPLACEMENT THERAPY; CORONARY-HEART-DISEASE; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; PLUS PROGESTIN; BREAST-CANCER; TRIAL; RISK; HEALTH AB Objective: We sought to understand the relationship among components of residency education about hormone therapy (HT), knowledge about HT, and provider attitudes toward HT during a time of rapidly changing practice guidelines. Methods: We surveyed residents in the University of Pittsburgh Internal Medicine residency programs between February to April 2002 (after the release of the Heart Estrogen/Progestin Replacement Study and prior to the release of preliminary Women's Health Initiative data) regarding demographics, educational (didactic and experiential) exposures to HT and menopause management, knowledge about HT, and attitudes toward HT. Results: Sixty-nine of 92 (75%) eligible residents completed the survey; 38% were women. The race and gender of responders did not differ from nonresponders. Residents had significant didactic exposure to HT and menopause management with 80% reporting more than one didactic exposure. Despite this, HT knowledge was low (mean knowledge score 47 +/- 16%) and only 26% of residents felt prepared to counsel patients about HT. We identified four factors related to provider attitudes toward HT: "persistence" in universally recommending HT, confidence in "HT benefits," concern about "HT cardiac risks," and concern about "HT noncardiac risks." More appropriate attitudes were associated with attending a lecture, having a rotation with a discussion of menopause management (i.e., Women's Health), and a continuity practice including more than 30% women. Pharmaceutical detailing and self-directed study were associated with less appropriate attitudes. Knowledge did not influence attitudes. Strongly held beliefs about the benefits of HT, appropriate or inappropriate, were associated with increasing "persistence." Conclusions: In an area of rapidly changing information, such as the risks and benefits of HT, knowledge is low. Experiential learning appropriately influences attitudes, while pharmaceutical detailing was associated with inappropriate attitudes toward HT risks. C1 Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Hess, R (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA. EM hessr@umpc.edu NR 27 TC 4 Z9 4 U1 1 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 JAN-FEB PY 2005 VL 15 IS 1 BP 31 EP 38 DI 10.1016/j.whi.2004.10.002 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 894HM UT WOS:000226781600005 PM 15661585 ER PT J AU Watkins, MT AF Watkins, MT TI Early research in the Department of Surgery, Uniformed Services University of the Health Sciences SO WORLD JOURNAL OF SURGERY LA English DT Article ID VEIN ENDOTHELIAL-CELLS; ARTERIAL PROSTHESES; VASCULAR PROSTHESES; REPRODUCTIVE CAPACITY; PLATELET SURVIVAL; MUCOSAL CELLS; GUINEA-PIG; DOGS; GRAFTS; RABBIT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Dept Surg, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg,Dept Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 24 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PY 2005 VL 29 SU 1 BP S108 EP S110 DI 10.1007/s00268-004-2076-9 PG 3 WC Surgery SC Surgery GA 936FG UT WOS:000229840300028 PM 15815817 ER PT J AU Beare, AHM Krane, SM Ferguson, MWJ AF Beare, AHM Krane, SM Ferguson, MWJ TI Variable impairment of wound healing in the heterozygous collagenase-resistant mouse SO WOUND REPAIR AND REGENERATION LA English DT Article ID SMOOTH MUSCLE ACTIN; TIGHT-SKIN MICE; TSK MUTANT MICE; EXTRACELLULAR-MATRIX; I COLLAGEN; INTERSTITIAL COLLAGENASE; GRANULATION-TISSUE; EXPRESSION; FIBROBLASTS; CONTRACTION AB Collagen undergoes dramatic reorganization during wound repair, Matrix metalloproteinases degrade and remodel collagen in a tightly controlled process, The collagenase-resistant mouse, Col1a1(fm1Jae), produces type I collagen, which is resistant to degradation by human matrix metalloproteinase 1. These mice grow normally but develop thickened skin with age. We have previously reported that the early wound repair response in homozygous mutant (Col1a1(r/r)) mice is delayed compared to wild type (Col1a1(+/+)). However, the late-stage scar of Col1a1(r/r) wounds was not significantly altered compared to Col1a1(+/+). Here we have investigated the response of heterozygous mice (Col1a1(+/r)) to wounding, not previously reported. Wound reepithelialization was delayed to a similar degree to wounds in the Col1a1(r/r) mice. However, the recovery of impaired wound contraction was faster in Col1a1(+/r) than in Col1a1(r/r) mice, but still slower than in wild-type animals. Analysis of wound protein extracts showed expression of some matrix metalloproteinases was prolonged in both the Col1a1(4/4) and Col1a1(+/+) wounds compared to wild type. We suggest the partial resistance of collagen to collagenase-mediated degradation in the heterozygous animals causes equivalent impairment of keratinocyte migration compared to homozygous collagenase-resistant mice, but that wound contraction during late-stage healing is only partially retarded. C1 Univ Manchester, United Kingdom Ctr Tissue Engn, Sch Biol Sci, Manchester M13 9PT, Lancs, England. Univ Manchester, Sch Biol Sci, Div Immunol Microbiol Dev & Repair, Manchester M13 9PT, Lancs, England. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Ferguson, MWJ (reprint author), Univ Manchester, United Kingdom Ctr Tissue Engn, Sch Biol Sci, 3-239 Stapford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM Mark.Ferguson@man.ac.uk NR 50 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 EI 1524-475X J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2005 VL 13 IS 1 BP 27 EP 40 DI 10.1111/j.1067-1927.2005.130105.x PG 14 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 897NU UT WOS:000227012700005 PM 15659034 ER PT J AU Mueller, NJ Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Wilkinson, RA Arn, S Sachs, DH Cooper, DKC Fishman, JA AF Mueller, NJ Kuwaki, K Knosalla, C Dor, FJMF Gollackner, B Wilkinson, RA Arn, S Sachs, DH Cooper, DKC Fishman, JA TI Early weaning of piglets fails to exclude porcine lymphotropic herpesvirus SO XENOTRANSPLANTATION LA English DT Article DE early weaning; pig; porcine cytomegalovirus; porcine lymphotropic herpesvirus; post-transplantation lymphoproliferative disorder; virus; xenotransplantation ID DNA-POLYMERASE LOCI; LYMPHOPROLIFERATIVE DISEASE; PIGS; XENOTRANSPLANTATION; CYTOMEGALOVIRUS; GAMMAHERPESVIRUSES; SIMILARITY; ACTIVATION AB Background: Xenotransplantation using pigs as source species carries a risk for the activation of latent herpesviruses from the porcine donor and potential transmission to the recipient. In pig-to-baboon xenotransplantation, activation of porcine cytomegalovirus (PCMV) has been associated with xenograft injury and an increased incidence of consumptive coagulopathy and graft loss. Activation of porcine lymphotropic herpesvirus (PLHV)-1 was not observed in pig-to-baboon solid organ xenotransplantation, but was associated with a syndrome of post-transplantation lymphoproliferative disorder (PTLD) after allogeneic stem cell transplantation in pigs. Material and Methods: Early weaning of piglets was used to try to reduce the viral burden of xenograft donors. This consisted of separating the piglets of a litter from the sow within the first 2 weeks after birth and raising them in isolation from the remaining herd. Results: We have previously demonstrated that PCMV could be excluded from source animals by early weaning of piglets. However, early weaning failed to exclude PLHV-1 from source pigs. Conclusions: This disparity between PCMV and PLHV-1 reflects differing pathogenesis of infection of these herpesviruses. New approaches will be needed to exclude PLHV-1 from pig colonies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. EM jfishman@partners.org RI Dor, Frank/E-1032-2013; Infektiologie, USZ/A-6921-2011; Mueller, Nicolas/B-6864-2013 OI Dor, Frank/0000-0001-7845-3075; Mueller, Nicolas/0000-0002-1059-3191 FU NIAID NIH HHS [5T32-AI07529-04, P01-AI45897] NR 16 TC 24 Z9 24 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2005 VL 12 IS 1 BP 59 EP 62 DI 10.1111/j.1399-3089.2004.00196.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 879VP UT WOS:000225747500008 PM 15598274 ER PT J AU Glaser, V Look, AT AF Glaser, Vicki Look, A. Thomas TI An Interview with A. Thomas Look, MD SO ZEBRAFISH LA English DT Editorial Material C1 [Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Look, A. Thomas] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2005 VL 2 IS 4 BP 231 EP 236 DI 10.1089/zeb.2005.2.231 PG 6 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18DK UT WOS:000207985300001 ER PT J AU Patton, EE Zon, LI AF Patton, E. Elizabeth Zon, Leonard I. TI Taking Human Cancer Genes to the Fish: A Transgenic Model of Melanoma in Zebrafish SO ZEBRAFISH LA English DT Review ID MALIGNANT-MELANOMA; BRAF MUTATIONS; XIPHOPHORUS; SUPPRESSION; GENETICS; OPINION; MOUSE C1 [Patton, E. Elizabeth; Zon, Leonard I.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. [Patton, E. Elizabeth; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Childrens Hosp, Boston, MA 02115 USA. [Patton, E. Elizabeth; Zon, Leonard I.] Harvard Univ, Sch Med, Div Hematol & Oncol, Childrens Hosp, Boston, MA 02115 USA. [Patton, E. Elizabeth; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU Human Frontiers Science Program Long-Term Fellowship; NIH FX This work was supported by a Human Frontiers Science Program Long-Term Fellowship (EEP) and NIH grants (LIZ). LIZ is an Investigator of the Howard Hughes Medical Institute. NR 27 TC 11 Z9 11 U1 3 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2005 VL 1 IS 4 BP 363 EP 368 DI 10.1089/zeb.2005.1.363 PG 6 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18CZ UT WOS:000207984200007 PM 18248215 ER PT J AU Ran, QT Liang, HY Gu, MJ Qi, WB Walter, CA Roberts, LJ Herman, B Richardson, A Van Remmen, H AF Ran, QT Liang, HY Gu, MJ Qi, WB Walter, CA Roberts, LJ Herman, B Richardson, A Van Remmen, H TI Transgenic mice overexpressing glutathione peroxidase 4 are protected against oxidative stress-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROPEROXIDE GLUTATHIONE-PEROXIDASE; LIPID-PEROXIDATION; OXIDANT STRESS; CYTOCHROME-C; DAMAGE; CELLS; INJURY; GENE; DIQUAT; PHGPX AB Glutathione peroxidase 4 (Gpx4) is uniquely involved in the detoxification of oxidative damage to membrane lipids. Our previous studies showed that Gpx4 is essential for mouse survival and that Gpx4 deficiency makes cells vulnerable to oxidative injury. In the present study, we generated two lines of transgenic mice overexpressing Gpx4 (Tg(GPX4) mice) using a genomic clone containing the human GPX4 gene. Both lines of Tg(GPX4) mice, Tg5 and Tg6, had elevated levels of Gpx4 (mRNA and protein) in all tissues investigated, and overexpression of Gpx4 did not cause alterations in activities of glutathione peroxidase 1, catalase, Cu/Zn superoxide dismutase, and manganese superoxide dismutase. The human GPX4 transgene rescued the lethal phenotype of null mutation of the mouse Gpx4 gene, indicating that the transgene can replace the essential role of mouse Gpx4 in mouse development. Cell death induced by t-butylhydroperoxide and diquat was significantly less in murine embryonic fibroblasts from Tg(GPX4) mice compared with wild type mice. Liver damage and lipid peroxidation induced by diquat were reduced significantly in Tg(GPX4) mice. In addition, diquat-induced apoptosis was decreased in Tg(GPX4) mice, as evidenced by attenuated caspase-3 activation and reduced cytochrome c release from mitochondria. These data demonstrate that Gpx4 plays a role in vivo in the mechanism of apoptosis induced by oxidative stress that most likely occurs through oxidative damage to mitochondrial phospholipids such as cardiolipin. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio Canc Inst, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. RP Van Remmen, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, GRECC 182, 7400 Merton Mintor Blvd, San Antonio, TX 78284 USA. EM vanremmen@uthscsa.edu RI Liang, Hanyu/A-1066-2010 FU NIA NIH HHS [1P30 AG 13319, K01 AG 22014, P01 AG 19316] NR 45 TC 121 Z9 125 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 DEC 31 PY 2004 VL 279 IS 53 BP 55137 EP 55146 DI 10.1074/jbc.M410387200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800020 PM 15496407 ER PT J AU Chen, JF Takagi, J Xie, C Xiao, T Luo, BH Springer, TA AF Chen, JF Takagi, J Xie, C Xiao, T Luo, BH Springer, TA TI The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin alpha(4)beta(7) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRIN ALPHA-V-BETA-3; EXTRACELLULAR SEGMENT; PHYSIOLOGICAL FLOW; CRYSTAL-STRUCTURE; ACTIVATION; AFFINITY; COMPLEX; LIGAND; CONFORMATION; SUBUNIT AB We examined the effect of conformational change at the beta(7) I-like/hybrid domain interface on regulating the transition between rolling and firm adhesion by integrin alpha(4)beta(7). An N-glycosylation site was introduced into the I-like/hybrid domain interface to act as a wedge and to stabilize the open conformation of this interface and hence the open conformation of the alpha(4)beta(7) headpiece. Wild-type alpha(4)beta(7) mediates rolling adhesion in Ca2+ and Ca2+/Mg2+ but firm adhesion in Mg2+ and Mn2+. Stabilizing the open headpiece resulted in firm adhesion in all divalent cations. The interaction between metal binding sites in the I-like domain and the interface with the hybrid domain was examined in double mutants. Changes at these two sites can either counterbalance one another or be additive, emphasizing mutuality and the importance of multiple interfaces in integrin regulation. A double mutant with counterbalancing deactivating ligand-induced metal ion binding site ( LIMBS) and activating wedge mutations could still be activated by Mn2+, confirming the importance of the adjacent to metal ion-dependent adhesion site (ADMIDAS) in integrin activation by Mn2+. Overall, the results demonstrate the importance of headpiece allostery in the conversion of rolling to firm adhesion. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Osaka Univ, Inst Prot Res, Lab Prot Synth & Express, Suita, Osaka 5650871, Japan. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Xiao, Tsan/A-8590-2010; Xiao, Tsan/I-7616-2013 OI Xiao, Tsan/0000-0001-9688-475X FU NHLBI NIH HHS [HL 48675, P01 HL048675]; NIAID NIH HHS [R01 AI072765] NR 36 TC 32 Z9 35 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 DEC 31 PY 2004 VL 279 IS 53 BP 55556 EP 55561 DI 10.1074/jbc.M407773200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 882TI UT WOS:000225960800072 PM 15448154 ER PT J AU Rosowsky, A Forsch, RA Wright, JE AF Rosowsky, A Forsch, RA Wright, JE TI Synthesis and in vitro antifolate activity of rotationally restricted aminopterin and methotrexate analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID GAMMA-GLUTAMYL HYDROLASE; SIDE-CHAIN; FOLIC-ACID; N(ALPHA)-(4-AMINO-4-DEOXYPTEROYL)-N(DELTA)-HEMIPHTHALOYL-L-ORNITHINE PT523; FOLYLPOLYGLUTAMATE SYNTHETASE; DIHYDROFOLATE-REDUCTASE; THYMIDYLATE SYNTHASE; ANTITUMOR-ACTIVITY; RESISTANCE; POTENT AB Heretofore unknown analogues of aminopterin (AMT) and methotrexate (MTX) in which free rotation of the amide bond between the phenyl ring and amino acid side chain is prevented by a CH2 bridge were synthesized and tested for in vitro antifolate activity. The K-i of the AMT analogue (9) against human dihydrofolate reductase (DHFR) was 34 pM, whereas that of the MTX analogue (10) was 2100 pM. Both compounds were less potent than the parent drugs. However, although the difference between AMT and MTX was < 2-fold, the difference between 9 and 10 was 62-fold, suggesting that the effect of N-10-methyl substitution is amplified in the bridged compounds. The K-i values of 9 and 10 as inhibitors of [H-3]MTX influx into CCRF-CEM human leukemia cells via the reduced folate carrier (RFC) were 0.28 and 1.1 muM, respectively. The corresponding K-i and K-t values determined earlier for AMT and MTX were 5.4 and 4.7 muM, respectively. Thus, in contrast to its unfavorable effect on DHFR binding, the CH2 bridge increased RFC binding. In a 72 h growth assay with CCRF-CEM cells, the IC50 valuess of 9 and 10 were 5.1 and 140 nM, respectively, a 27-fold difference that was qualitatively consistent with the observed combination of weaker DHFR binding and stronger RFC binding. Although rotationally restricted inhibitors of other enzymes of folate pathway enzymes have been described previously, 9 and 10 are the first reported examples of DHFR inhibitors of this type. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andre_rosowsky@dfci.harvard.edu FU NCI NIH HHS [R01-CA25394] NR 28 TC 7 Z9 8 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 30 PY 2004 VL 47 IS 27 BP 6958 EP 6963 DI 10.1021/jm040122s PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 882QC UT WOS:000225952400034 PM 15615544 ER PT J AU McFalls, EO Ward, HB Moritz, TE Goldman, S Krupski, WC Littooy, F Pierpont, G Santilli, S Rapp, J Hattler, B Shunk, K Jaenicke, C Thottapurathu, L Ellis, N Reda, DJ Henderson, WG AF McFalls, EO Ward, HB Moritz, TE Goldman, S Krupski, WC Littooy, F Pierpont, G Santilli, S Rapp, J Hattler, B Shunk, K Jaenicke, C Thottapurathu, L Ellis, N Reda, DJ Henderson, WG TI Coronary-artery revascularization before elective major vascular surgery SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONCARDIAC SURGERY; BYPASS-SURGERY; CARDIAC RISK; MYOCARDIAL-INFARCTION; DISEASE; ANGIOPLASTY; GUIDELINE; MORTALITY; SURVIVAL; OUTCOMES AB BACKGROUND: The benefit of coronary-artery revascularization before elective major vascular surgery is unclear. METHODS: We randomly assigned patients at increased risk for perioperative cardiac complications and clinically significant coronary artery disease to undergo either revascularization or no revascularization before elective major vascular surgery. The primary end point was long-term mortality. RESULTS: Of 5859 patients scheduled for vascular operations at 18 Veterans Affairs medical centers, 510 (9 percent) were eligible for the study and were randomly assigned to either coronary-artery revascularization before surgery or no revascularization before surgery. The indications for a vascular operation were an expanding abdominal aortic aneurysm (33 percent) or arterial occlusive disease of the legs (67 percent). Among the patients assigned to preoperative coronary-artery revascularization, percutaneous coronary intervention was performed in 59 percent, and bypass surgery was performed in 41 percent. The median time from randomization to vascular surgery was 54 days in the revascularization group and 18 days in the group not undergoing revascularization (P<0.001). At 2.7 years after randomization, mortality in the revascularization group was 22 percent and in the no-revascularization group 23 percent (relative risk, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.92). Within 30 days after the vascular operation, a postoperative myocardial infarction, defined by elevated troponin levels, occurred in 12 percent of the revascularization group and 14 percent of the no-revascularization group (P=0.37). CONCLUSIONS: Coronary-artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary-artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended. C1 Vet Adm Med Ctr, Div Cardiol, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Med, Div Cardiol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. Univ Minnesota, Div Cardiovasc & Thorac Surg, Minneapolis, MN 55455 USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. Vet Affairs Med Ctr, Div Peripheral Vasc Surg, Hines, IL USA. So Arizona VA Hlth Care Syst, Tucson, AZ USA. Univ Arizona, Sarver Heart Ctr, Tucson, AZ USA. Denver VA Med Ctr, Denver, CO USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94143 USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Univ Colorado, Dept Prevent Med & Biometr, Denver, CO 80202 USA. RP McFalls, EO (reprint author), Vet Adm Med Ctr, Div Cardiol, 1 Vet Dr, Minneapolis, MN 55417 USA. EM mcfal001@tc.umn.edu NR 24 TC 567 Z9 593 U1 1 U2 9 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 DEC 30 PY 2004 VL 351 IS 27 BP 2795 EP 2804 DI 10.1056/NEJMoa041905 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300004 PM 15625331 ER PT J AU Gragoudas, ES Adamis, AP Cunningham, ET Feinsod, M Guyer, DR AF Gragoudas, ES Adamis, AP Cunningham, ET Feinsod, M Guyer, DR CA VEGF Inhibition Study Ocular Neova TI Pegaptanib for neovascular age-related macular degeneration SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROLIFERATIVE DIABETIC-RETINOPATHY; CHOROIDAL NEOVASCULARIZATION; NONHUMAN PRIMATE; IRIS NEOVASCULARIZATION; INHIBITION; RNA AB BACKGROUND: Pegaptanib, an anti-vascular endothelial growth factor therapy, was evaluated in the treatment of neovascular age-related macular degeneration. METHODS: We conducted two concurrent, prospective, randomized, double-blind, multicenter, dose-ranging, controlled clinical trials using broad entry criteria. Intravitreous injection into one eye per patient of pegaptanib (at a dose of 0.3 mg, 1.0 mg, or 3.0 mg) or sham injections were administered every 6 weeks over a period of 48 weeks. The primary end point was the proportion of patients who had lost fewer than 15 letters of visual acuity at 54 weeks. RESULTS: In the combined analysis of the primary end point (for a total of 1186 patients), efficacy was demonstrated, without a dose-response relationship, for all three doses of pegaptanib (P<0.001 for the comparison of 0.3 mg with sham injection; P<0.001 for the comparison of 1.0 mg with sham injection; and P=0.03 for the comparison of 3.0 mg with sham injection). In the group given pegaptanib at 0.3 mg, 70 percent of patients lost fewer than 15 letters of visual acuity, as compared with 55 percent among the controls (P<0.001). The risk of severe loss of visual acuity (loss of 30 letters or more) was reduced from 22 percent in the sham-injection group to 10 percent in the group receiving 0.3 mg of pegaptanib (P<0.001). More patients receiving pegaptanib (0.3 mg), as compared with sham injection, maintained their visual acuity or gained acuity (33 percent vs. 23 percent; P=0.003). As early as six weeks after beginning therapy with the study drug, and at all subsequent points, the mean visual acuity among patients receiving 0.3 mg of pegaptanib was better than in those receiving sham injections (P<0.002). Among the adverse events that occurred, endophthalmitis (in 1.3 percent of patients), traumatic injury to the lens (in 0.7 percent), and retinal detachment (in 0.6 percent) were the most serious and required vigilance. These events were associated with a severe loss of visual acuity in 0.1 percent of patients. CONCLUSIONS: Pegaptanib appears to be an effective therapy for neovascular age-related macular degeneration. Its long-term safety is not known. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Eyetech Pharmaceut, New York, NY USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM evangelos_gragoudas@meei.harvard.edu RI Schlingemann, Reinier/E-6287-2013; Larsen, Michael/E-9620-2010 OI Larsen, Michael/0000-0002-5172-5891 NR 24 TC 1398 Z9 1479 U1 2 U2 71 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 DEC 30 PY 2004 VL 351 IS 27 BP 2805 EP 2816 DI 10.1056/NEJMoa042760 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300005 PM 15625332 ER PT J AU Steele, DJR Michaels, PJ Goes, N Cornell, LD AF Steele, DJR Michaels, PJ Goes, N Cornell, LD TI A woman with long-standing hematuria - Nephropathy with thin and focally disrupted glomerular basement membranes and decreased alpha 3 and alpha 5 chains of type IV collagen, consistent with a carrier state of X-linked Alport's syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ISOLATED MICROSCOPIC HEMATURIA; IGA NEPHROPATHY; DISEASE; ADULTS; GENE C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, 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 Pathol, Cambridge, MA 02138 USA. RP Steele, DJR (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. NR 23 TC 1 Z9 2 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 DEC 30 PY 2004 VL 351 IS 27 BP 2851 EP 2859 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300012 PM 15625337 ER PT J AU Ritsher, JB Phelan, JC AF Ritsher, JB Phelan, JC TI Internalized stigma predicts erosion of morale among psychiatric outpatients SO PSYCHIATRY RESEARCH LA English DT Article; Proceedings Paper CT Biennial Congress of the World-Federation-for-Mental-Health CY FEB, 2003 CL Melbourne, AUSTRALIA SP World Federat Mental Hlth DE severe mental illness (SMI); mental disorders; stereotyping; social alienation; risk factors; depressive symptoms ID MENTAL-ILLNESS; PERCEIVED STIGMA; CONSEQUENCES; DISORDERS; REJECTION; PEOPLE; HEALTH AB Stigma in society causes harm to people with severe mental illness (SMI) and internalized stigma represents its psychological point of impact. We evaluated the extent of internalized stigma in a sample of outpatients with SMI, using the Internalized Stigma of Mental Illness (ISMI) scale, developed with consumer input. About a third of the sample reported high levels of internalized stigma. We tested whether internalized stigma predicted increased depressive symptoms and reduced self-esteem at 4-month follow-up, controlling for baseline levels. Depression was predicted by Alienation, Stereotype Endorsement, Social Withdrawal Scales and total ISMI score. Reduced self-esteem was predicted by Alienation. ISMI results were stronger than those for the widely used Devaluation-Discrimination Scale. The finding that alienation further reduces morale speaks to the difficulty of pulling oneself out of this type of vicious cycle without assistance. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY 10032 USA. RP Ritsher, JB (reprint author), Univ Calif San Francisco, Dept Psychiat, 116A,4150 Clement St, San Francisco, CA 94121 USA. EM ritsher@itsa.ucsf.edu FU NIMH NIH HHS [K2MH65330] NR 27 TC 220 Z9 228 U1 3 U2 22 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 30 PY 2004 VL 129 IS 3 BP 257 EP 265 DI 10.1016/j.psychres.2004.08.003 PG 9 WC Psychiatry SC Psychiatry GA 897HA UT WOS:000226993400005 PM 15661319 ER PT J AU Miller, KK Deckersbach, T Rauch, SL Fischman, AJ Grieco, KA Herzog, DB Klibanski, A AF Miller, KK Deckersbach, T Rauch, SL Fischman, AJ Grieco, KA Herzog, DB Klibanski, A TI Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE androgens; posterior cingulate gyrus; positron emission tomography; women's health; eating disorders ID POSITRON-EMISSION-TOMOGRAPHY; OBSESSIVE-COMPULSIVE DISORDER; EATING-DISORDERS; GLUCOSE-METABOLISM; HYPOGONADAL MEN; SEXUAL FUNCTION; REFRACTORY DEPRESSION; REPLACEMENT THERAPY; HUNTINGTONS-DISEASE; PEDIATRIC-PATIENTS AB Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and fight parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions - the posterior cingulate cortex - were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings. as well as to determine their physiological and clinical significance. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B, Boston, MA 02114 USA. EM KKMiller@Partners.org FU NCRR NIH HHS [M01-RR01066-27, M01-RR01066-27S1]; NIDDK NIH HHS [R01-DK52625, R03-DK59297]; NIMH NIH HHS [MH 60219] NR 56 TC 31 Z9 32 U1 5 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 30 PY 2004 VL 132 IS 3 BP 197 EP 207 DI 10.1016/j.psychresns.2004.09.003 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 897HX UT WOS:000226995700001 PM 15664791 ER PT J AU Chin, PS Branch, KR Becker, KJ AF Chin, PS Branch, KR Becker, KJ TI Myocardial infarction following brief convulsive seizures SO NEUROLOGY LA English DT Editorial Material ID REFRACTORY EPILEPSY C1 Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Med Ctr, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Neurol Surg, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Div Cardiol, Seattle, WA 98195 USA. Univ Calif Los Angeles, Dept Med, Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Robert Wood Johnson VA Clin Scholars Program, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Becker, KJ (reprint author), Univ Washington, Harborview Med Ctr, Box 359775,325 9th Ave, Seattle, WA 98104 USA. EM kjb@u.washington.edu NR 7 TC 24 Z9 24 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 DEC 28 PY 2004 VL 63 IS 12 BP 2453 EP 2454 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 883KJ UT WOS:000226010000064 PM 15623737 ER PT J AU Sasaki, Y Watanabe, T AF Sasaki, Y Watanabe, T TI The primary visual cortex fills in color SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE filling-in; functional MRI; transparency ID LATERAL GENICULATE-NUCLEUS; SUBJECTIVE CONTOURS; CORTICAL AREAS; BLIND-SPOT; ATTENTION; SURFACES; REPRESENTATION; RESPONSES; DYNAMICS; TRANSPARENCY AB One of the most important goals of visual processing is to reconstruct adequate representations of surfaces in a scene. It is thought that surface representation is produced mainly in the midlevel vision and that area V1 (the primary visual cortex) activity is solely due to feedback from the midlevel stage. Here, we measured functional MRI signals corresponding to "neon color spreading": an illusory transparent surface with long-range color filling-in, one of the important mediums in reconstructing a surface. The experiment was conducted with careful controls of attention, which can send feedback signals from higher visual areas. Activity for filling-in was observed only in V1, whereas activity for illusory contours was observed in multiple visual areas. These results indicate that surface representation is produced by multiple rather than single processing. C1 Boston Univ, Dept Psychol, Boston, MA 02115 USA. Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. RP Watanabe, T (reprint author), Boston Univ, Dept Psychol, Boston, MA 02115 USA. EM takeo@bu.edu FU NEI NIH HHS [R01EY015980, R01 EY015980] NR 51 TC 74 Z9 74 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 28 PY 2004 VL 101 IS 52 BP 18251 EP 18256 DI 10.1073/pnas.0406293102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 884RD UT WOS:000226102700066 PM 15596726 ER PT J AU Chan, Y Zimmer, JP Stroh, M Steckel, JS Jain, RK Bawendi, MG AF Chan, Y Zimmer, JP Stroh, M Steckel, JS Jain, RK Bawendi, MG TI Incorporation of luminescent nanocrystals into monodisperse core-shell silica microspheres SO ADVANCED MATERIALS LA English DT Article ID QUANTUM DOTS; TUMOR VESSELS; SPHERES; SIZE; NANOPARTICLES; FABRICATION; PARTICLES; PATHWAYS; CRYSTALS AB Silica microspheres coated with a silica or titania shell containing fluorescent semiconductor nanocrystals are described. Since the coating process does not affect the monodispersity of the silica microspheres, microspheres of a defined size and emission wavelength, potentially useful for biological applications, can be fabricated. The Figure shows 100 nm diameter blue-light-emitting and 500 nm diameter red-light-emitting microspheres circulating in the brain of a mouse. C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Bawendi, MG (reprint author), MIT, Dept Chem, 77 Massachusetts Ave,Room 6-221, Cambridge, MA 02139 USA. EM mgb@mit.edu OI Chan, YinThai/0000-0002-8471-9009 NR 28 TC 185 Z9 192 U1 7 U2 60 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0935-9648 J9 ADV MATER JI Adv. Mater. PD DEC 27 PY 2004 VL 16 IS 23-24 BP 2092 EP + DI 10.1002/adma.200400237 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 886KD UT WOS:000226225000003 ER PT J AU Yamanaka, M Shegogue, D Pei, HP Bu, SZ Bielawska, A Bielawski, J Pettus, B Hannun, YA Obeid, L Trojanowska, M AF Yamanaka, M Shegogue, D Pei, HP Bu, SZ Bielawska, A Bielawski, J Pettus, B Hannun, YA Obeid, L Trojanowska, M TI Sphingosine kinase 1 (SPHK1) is induced by transforming growth factor-beta and mediates TIMP-1 up-regulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DERMAL FIBROBLASTS; GENE-EXPRESSION; TISSUE INHIBITOR; KINASE-ACTIVITY; ONCOSTATIN-M; PROTEIN; SPHINGOSINE-1-PHOSPHATE; ACTIVATION; INTERACTS; METALLOPROTEINASE-1 AB Transforming growth factor-beta(TGF-beta) signaling plays a pivotal role in extracellular matrix deposition by stimulating collagen production and other extracellular matrix proteins and by inhibiting matrix degradation. The present study was undertaken to define the role of sphingosine kinase (SphK) in TGF-beta signaling. TGF-beta markedly up-regulated SphK1 mRNA and protein amounts and caused a prolonged increase in SphK activity in dermal fibroblasts. Concomitantly, TGF-beta reduced sphingosine-1-phosphate phosphatase activity. Consistent with the changes in enzyme activity, corresponding changes in sphingolipid levels were observed such that sphingosine 1-phosphate (S1P) was increased (similar to2-fold), whereas sphingosine and ceramide were reduced after 24 h of TGF-beta treatment. Given the relatively early induction of SphK gene expression in response to TGF-beta, we examined whether SphK1 may be involved in the regulation of TGF-beta-inducible genes that exhibit compatible kinetics, e.g. tissue inhibitor of metalloproteinase-1 (TIMP-1). We demonstrate that decreasing SphK1 expression by small interfering RNA (siRNA) blocked TGF-beta-mediated up-regulation of TIMP-1 protein suggesting that up-regulation of SphK1 contributes to the induction of TIMP-1 in response to TGF-beta. The role of SphK1 as a positive regulator of TIMP-1 gene expression was further corroborated by using ectopically expressed SphK1 in the absence of TGF-beta. Adenovirally expressed SphK1 led to a 2-fold increase of endogenous S1P and to increased TIMP-1 mRNA and protein production. In addition, ectopic SphK1 and TGF-beta cooperated in TIMP-1 up-regulation. Mechanistically, experiments utilizing TIMP-1 promoter constructs demonstrated that the action of SphK1 on the TIMP-1 promoter is through the AP1-response element, consistent with the SphK1-mediated up-regulation of phospho-c-Jun levels, a key component of AP1. Together, these experiments demonstrate that SphK/S1P are important components of the TGF-beta signaling pathway involved in up-regulation of the TIMP-1 gene. C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29425 USA. RP Trojanowska, M (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Ste 912, Charleston, SC 29425 USA. EM trojanme@musc.edu OI Trojanowska, Maria/0000-0001-9550-7178 FU NIA NIH HHS [AG16538]; NIAMS NIH HHS [P60 AR049459]; NIGMS NIH HHS [GM43825] NR 45 TC 74 Z9 79 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 53994 EP 54001 DI 10.1074/jbc.M410144200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600014 PM 15485866 ER PT J AU Li, Z David, G Hung, KW DePinho, RA Fu, AKY Ip, NY AF Li, Z David, G Hung, KW DePinho, RA Fu, AKY Ip, NY TI Cdk5/p35 phosphorylates mSds3 and regulates mSds3-mediated repression of transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT KINASE-5; HISTONE DEACETYLASE ACTIVITY; COREPRESSOR COMPLEX; NEURONAL MIGRATION; INTEGRAL COMPONENT; GENE-TRANSCRIPTION; INDUCED APOPTOSIS; NERVOUS-SYSTEM; PROTEIN-KINASE; BOVINE BRAIN AB Cyclin-dependent kinase 5 (Cdk5), a serine/threonine kinase that displays kinase activity predominantly in neurons, is activated by two non-cyclin activators, p35 or p39. Here, we report a physical and functional interaction between the Cdk5/p35 complex and mouse Sds3 (mSds3), an essential component of mSin3-histone deacetylase ( HDAC) co-repressor complex. mSds3 binds to p35 both in vitro and in vivo, enabling active Cdk5 to phosphorylate mSds3 at serine 228. A mSds3 S228A mutant retained mSin3 binding activity, but its dimerization was not greatly enhanced by p35 when compared with wild type. Notably, p35 overexpression augmented mSds3-mediated transcriptional repression in vitro. Interestingly, mutational studies revealed that the ability of exogenous mSds3 to rescue cell growth and viability in mSds3 null cells correlates with its ability to be phosphorylated by Cdk5. The identification of mSds3 as a substrate of the Cdk5/p35 complex reveals a new regulatory mechanism in controlling the mSin3-HDAC transcriptional repressor activity and provides a new potential therapeutic means to inhibit specific HDAC activities in disease. C1 Hong Kong Univ Sci & Technol, Dept Biochem, Biotechnol Res Inst, Clear Water Bay, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Mol Neurosci Ctr, Clear Water Bay, Hong Kong, Peoples R China. Dana Farber Canc Inst, Dept Med Oncol Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ip, NY (reprint author), Hong Kong Univ Sci & Technol, Dept Biochem, Biotechnol Res Inst, Clear Water Bay, Hong Kong, Peoples R China. EM BOIP@UST.HK OI , gregory/0000-0002-3371-4558 FU NCI NIH HHS [R01CA86379] NR 40 TC 24 Z9 30 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 DEC 24 PY 2004 VL 279 IS 52 BP 54438 EP 54444 DI 10.1074/jbc.M411002200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600066 PM 15489224 ER PT J AU Nelson, EA Walker, SR Alvarez, JV Frank, DA AF Nelson, EA Walker, SR Alvarez, JV Frank, DA TI Isolation of unique STAT5 targets by chromatin immunoprecipitation-based gene identification SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN D1 PROMOTER; BCL-X GENE; BINDING-SITES; GENOMIC SITES; EXPRESSION; TRANSCRIPTION; PROTEINS; GROWTH; CELLS; CIS AB STAT5a and STAT5b are two highly related transcription factors that control essential cellular functions. Several STAT5 targets are known, although it is likely that most remain uncharacterized. To identify a more complete set of STAT5-regulated genes, we used a modification of the chromatin immunoprecipitation procedure, which does not presuppose any information regarding these targets. Employing Ba/f3 cells in which STAT5 is activated by interleukin-3, we have identified novel STAT5 binding sites that may be regulatory regions for nearby genes. These sites are typically found far from transcription start sites, and most do not contain CpG islands, indicating that they are not in traditional promoter regions. Nonetheless, when the expression of genes near these STAT5 binding sites was examined, all were expressed in Ba/f3 cells, and most were modulated by interleukin-3. Furthermore, genes identified by this strategy show unique expression patterns in acute leukemias, tumors characterized by activated STAT5. Whereas both STAT5 isoforms bound to all promoters tested, STAT5a and STAT5b bound with different kinetics, suggesting that at least some of the differences between the functions of these two proteins are mediated by their DNA binding activity. Therefore, this method of transcription factor target identification represents an effective strategy to isolate transcription factor targets in an unbiased fashion, and it has revealed many novel STAT5-dependent regulatory regions outside of traditional promoters. 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, Rm M552B,44 Binney St, Boston, MA 02115 USA. EM david_frank@dfci.harvard.edu FU NCI NIH HHS [CA79547] NR 41 TC 52 Z9 53 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 DEC 24 PY 2004 VL 279 IS 52 BP 54724 EP 54730 DI 10.1074/jbc.M408464200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600100 PM 15498775 ER PT J AU Gray, PA Fu, H Luo, P Zhao, Q Yu, J Ferrari, A Tenzen, T Yuk, DI Tsung, EF Cai, ZH Alerta, JA Cheng, LP Liu, Y Stenman, JM Valerius, MT Billings, N Kim, HA Greenberg, ME McMahon, AP Rowitch, DH Stiles, CD Ma, QF AF Gray, PA Fu, H Luo, P Zhao, Q Yu, J Ferrari, A Tenzen, T Yuk, DI Tsung, EF Cai, ZH Alerta, JA Cheng, LP Liu, Y Stenman, JM Valerius, MT Billings, N Kim, HA Greenberg, ME McMahon, AP Rowitch, DH Stiles, CD Ma, QF TI Mouse brain organization revealed through direct genome-scale TF expression analysis SO SCIENCE LA English DT Article ID GENE; MUTATIONS; PROFILES; SEQUENCE; DISORDER AB In the developing brain, transcription factors (TFs) direct the formation of a diverse array of neurons and glia. We identified 1445 putative TFs in the mouse genome. We used in situ hybridization to map the expression of over 1000 of these TFs and TF-coregulator genes in the brains of developing mice. We found that 349 of these genes showed restricted expression patterns that were adequate to describe the anatomical organization of the brain. We provide a comprehensive inventory of murine TFs and their expression patterns in a searchable brain atlas database. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM Charles-Stiles@dfci.harvard.edu; Qiufu_Ma@dfci.harvard.edu RI Fu, Hui/C-2881-2011 NR 18 TC 271 Z9 274 U1 0 U2 13 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 DEC 24 PY 2004 VL 306 IS 5705 BP 2255 EP 2257 DI 10.1126/science.1104935 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PE UT WOS:000225950000046 PM 15618518 ER PT J AU Oettinger, MA AF Oettinger, MA TI Molecular biology - Hairpins at split ends in DNA SO NATURE LA English DT Editorial Material ID V(D)J RECOMBINATION; TRANSPOSITION; TRANSPOSASES; RAG2 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Oettinger, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. EM oettinger@frodo.mgh.harvard.edu NR 14 TC 4 Z9 4 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 23 PY 2004 VL 432 IS 7020 BP 960 EP 961 DI 10.1038/432960b PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881RL UT WOS:000225887000023 PM 15616542 ER PT J AU O'Donnell, WJ Kradin, RL Evins, AE Wittram, C AF O'Donnell, WJ Kradin, RL Evins, AE Wittram, C TI Case 39-2004: A 52-year-old woman with recurrent episodes of atypical pneumonia - Smoking-related interstitial lung disease (respiratory bronchiolitis with interstitial lung disease desquamative interstitial pneumonitis) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PULMONARY ALVEOLAR PROTEINOSIS; CIGARETTE-SMOKING; SCHIZOPHRENIA; CESSATION; NICOTINE; SMOKERS; SPECTRUM; TRIAL C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, 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 Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP O'Donnell, WJ (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 36 TC 6 Z9 6 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 DEC 23 PY 2004 VL 351 IS 26 BP 2741 EP 2749 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 881OR UT WOS:000225877300011 PM 15616209 ER PT J AU Xie, AY Puget, N Shim, I Odate, S Jarzyna, I Bassing, CH Alt, FW Scully, R AF Xie, AY Puget, N Shim, I Odate, S Jarzyna, I Bassing, CH Alt, FW Scully, R TI Control of sister chromatid recombination by histone H2AX SO MOLECULAR CELL LA English DT Article ID DOUBLE-STRAND BREAK; DNA-DAMAGE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; GENOMIC INSTABILITY; IONIZING-RADIATION; REPAIR; PHOSPHORYLATION; SUPPRESSOR; BRCA1; MDC1 AB Histone H2AX has a role in suppressing genomic instability and cancer. However, the mechanisms by which it performs these functions are poorly understood. After DNA breakage, H2AX is phosphorylated on serine 139 in chromatin near the break. We show here that H2AX serine 139 enforces efficient homologous recombinational repair of a chromosomal double-strand break (DSB) by using the sister chromatid as a template. BRCA1, Rad51, and CHK2 contribute to recombinational repair, in part independently of H2AX H2AX(-/-) cells show increased use of single-strand annealing, an error-prone deletional mechanism of DSB repair. Therefore, the chromatin response around a chromosomal DSB, in which H2AX serine 139 phosphorylation plays a central role, "shapes" the repair process in favor of potentially error-free interchromatid homologous recombination at the expense of error-prone repair. H2AX phosphorylation may help set up a favorable disposition between sister chromatids. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Scully, R (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA. EM rscully@bidmc.harvard.edu RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [R01 CA095175, CA109901, CA92625, CA95175, K01 CA079576, P01 CA092625, P01 CA109901, R01 CA095175-03] NR 39 TC 141 Z9 147 U1 2 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC 22 PY 2004 VL 16 IS 6 BP 1017 EP 1025 DI 10.1016/j.molcel.2004.12.007 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 882IR UT WOS:000225933100015 PM 15610743 ER PT J AU Lorberbaum, JP Kose, S Johnson, MR Arana, GW Sullivan, LK Hamner, MB Ballenger, JC Lydiard, BR Brodrick, PS Bohning, DE George, MS AF Lorberbaum, JP Kose, S Johnson, MR Arana, GW Sullivan, LK Hamner, MB Ballenger, JC Lydiard, BR Brodrick, PS Bohning, DE George, MS TI Neural correlates of speech anticipatory anxiety in generalized social phobia SO NEUROREPORT LA English DT Article DE anticipatory anxiety; anxiety; fear; fMRI; functional magnetic resonance imaging; public speaking; social anxiety; social anxiety disorder; social phobia ID CEREBRAL-BLOOD-FLOW; MEDIAL PREFRONTAL CORTEX; AMYGDALA ACTIVATION; PUBLIC SPEAKING; HUMANS; PAIN; FACES; PET AB Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole) - regions important in automatic emotional processing - and less cortical activity (dorsal anterior cingulate/prefrontal cortex) -regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Lorberbaum, JP (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. EM lorberjp@musc.edu NR 25 TC 156 Z9 159 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 22 PY 2004 VL 15 IS 18 BP 2701 EP 2705 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 886XQ UT WOS:000226266800003 PM 15597038 ER PT J AU Jaaskelainen, IP Ojanen, V Ahveninen, J Auranen, T Levanen, S Mottonen, R Tarnanen, I Sams, M AF Jaaskelainen, IP Ojanen, V Ahveninen, J Auranen, T Levanen, S Mottonen, R Tarnanen, I Sams, M TI Adaptation of neuromagnetic N1 responses to phonetic stimuli by visual speech in humans SO NEUROREPORT LA English DT Article DE audio-visual integration; cortical adaptation; human auditory cortex; magnetoencephalography; NIm response; phonetic; vowel ID HUMAN AUDITORY-CORTEX; HUMAN BRAIN; SOUNDS; PERCEPTION AB The technique of 306-channel magnetoencephalogaphy (MEG) was used in eight healthy volunteers to test whether silent lip-reading modulates auditory-cortex processing of phonetic sounds. Auditory test stimuli (either Finnish vowel /ae/ or /o/) were preceded by a 500 ms lag by either another auditory stimulus (/ae/, /o/ or the second-formant midpoint between /ae/ and /o/), or silent movie of a person articulating /ae/ or /o/. Compared with NI responses to auditory /ae/ and /o/ when presented without a preceding stimulus, the amplitudes of left-hemisphere NI responses to the test stimuli were significantly suppressed both when preceded by auditory and visual stimuli, this effect being significantly stronger with preceding auditory stimuli. This suggests that seeing articulatory gestures of a speaker influences auditory speech perception by modulating the responsiveness of auditory-cortex neurons. C1 Helsinki Univ Technol, Lab Computat Engn, FIN-02015 Espoo, Finland. Harvard Univ, Massachusetts Gen Hosp, MIT, Med Sch Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Univ Helsinki, Cent Hosp, Biomag Lab, Helsinki, Finland. Helsinki Univ Technol, Low Temp Lab, FIN-02150 Espoo, Finland. RP Jaaskelainen, IP (reprint author), Helsinki Univ Technol, Lab Computat Engn, POB 9203,Innopoli 2,Tekniikant 14, FIN-02015 Espoo, Finland. EM iiro.jaaskelainen@hut.fi RI Jaaskelainen, Iiro/C-7392-2012; Sams, Mikko/G-7060-2012; Auranen, Toni/J-7137-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; FU NICHD NIH HHS [R01 HD040712] NR 20 TC 25 Z9 25 U1 9 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 22 PY 2004 VL 15 IS 18 BP 2741 EP 2744 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 886XQ UT WOS:000226266800010 PM 15597045 ER PT J AU Asch, SM McGlynn, EA Hogan, MM Hayward, RA Shekelle, P Rubenstein, L Keesey, J Adams, J Kerr, EA AF Asch, SM McGlynn, EA Hogan, MM Hayward, RA Shekelle, P Rubenstein, L Keesey, J Adams, J Kerr, EA TI Comparison of quality of care for patients in the Veterans Health Administration and patients in a national sample SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; STANDARDIZED PATIENTS; UNITED-STATES; SYSTEM; AFFAIRS; VA; MANAGEMENT; UNDERUSE; SURGERY; TOOL AB Background: The Veterans Health Administration (VITA) has introduced an integrated electronic medical record, performance measurement, and other system changes directed at improving care. Recent comparisons with other delivery systems have been limited to a small set of indicators. Objective: To compare the quality of VITA care with that of care in a national sample by using a comprehensive quality-of-care measure. Design: Cross-sectional comparison. Setting: 12 VITA health care systems and 12 communities. Patients: 596 VITA patients and 992 patients identified through random-digit dialing. All were men older than 35 years of age. Measurements: Between 1997 and 2000, quality was measured by using a chart-based quality instrument consisting of 348 indicators targeting 26 conditions. Results were adjusted for clustering, age, number of visits, and medical conditions. Results: Patients from the VITA scored significantly higher for adjusted overall quality (67% vs. 51%; difference, 16 percentage points [95% CI, 14 to 18 percentage points]), chronic disease care (72% vs. 59%; difference, 13 percentage points [CI, 10 to 17 percentage points]), and preventive care (64% vs. 44%; difference, 20 percentage points [CI, 12 to 28 percentage points]), but not for acute care. The VITA advantage was most prominent in processes targeted by VITA performance measurement (66% vs. 43%; difference, 23 percentage points [CI, 21 to 26 percentage points]) and least prominent in areas unrelated to VITA performance measurement (55% vs. 50%; difference, 5 percentage points [CI, 0 to 10 percentage points]). Limitations: Unmeasured residual differences in patient characteristics, a lower response rate in the national sample, and differences in documentation practices could have contributed to some of the observed differences. Conclusions: Patients from the VITA received higher-quality care according to a broad measure. Differences were greatest in areas where the VITA has established performance measures and actively monitors performance. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RAND Hlth, Santa Monica, CA USA. Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Asch, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Mail Code 111G, Los Angeles, CA 90073 USA. EM Steven.Asch@med.va.gov FU AHRQ HHS [5U18HS09463-03] NR 42 TC 328 Z9 329 U1 1 U2 8 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 DEC 21 PY 2004 VL 141 IS 12 BP 938 EP 945 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 882EY UT WOS:000225923000005 PM 15611491 ER PT J AU Lindenfeld, J Miller, GG Shakar, SF Zolty, R Lowes, BD Wolfel, EE Mestroni, L Page, RL Kobashigawa, J AF Lindenfeld, J Miller, GG Shakar, SF Zolty, R Lowes, BD Wolfel, EE Mestroni, L Page, RL Kobashigawa, J TI Drug therapy in the heart transplant recipient - Part II: Immunosuppressive drugs SO CIRCULATION LA English DT Article DE transplantation; drugs; immune system; rejection ID MYCOPHENOLATE MOFETIL RS-61443; CARDIAC ALLOGRAFT-REJECTION; CYCLOSPORINE MICROEMULSION; RANDOMIZED MULTICENTER; RENAL-TRANSPLANTATION; RAPAMYCIN AY-22,989; CLINICAL-EXPERIENCE; COMBINATION THERAPY; TACROLIMUS FK506; LIVER-TRANSPLANT C1 Univ Colorado, Hlth Sci Ctr, Div Cardiol, Ctr Womens Hlth Res, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Lindenfeld, J (reprint author), Univ Colorado, Hlth Sci Ctr, Div Cardiol, Ctr Womens Hlth Res, 4200 E 9th Ave,B-130, Denver, CO 80262 USA. EM joann.lindenfeld@UCHSC.edu OI Lowes, Brian/0000-0002-5919-2540; Mestroni, Luisa/0000-0003-1116-2286 NR 73 TC 80 Z9 82 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 21 PY 2004 VL 110 IS 25 BP 3858 EP 3865 DI 10.1161/01.CIR.0000150332.42276.69 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 881CT UT WOS:000225841700018 PM 15611389 ER PT J AU MacRae, CA Ellinor, PT AF MacRae, CA Ellinor, PT TI Genetic screening and risk assessment in hypertrophic cardiomyopathy - Editorial comment SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID MUTATIONS; SPECTRUM C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Cardiac Arrhytmia Serv, Boston, MA 02129 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. EM macrae@cvrc.mgh.harvard.edu NR 9 TC 8 Z9 9 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 DEC 21 PY 2004 VL 44 IS 12 BP 2326 EP 2328 DI 10.1016/j.jacc.2004.09.032 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 882GE UT WOS:000225926400006 PM 15607393 ER PT J AU Murthy, SK Sin, A Tompkins, RG Toner, M AF Murthy, SK Sin, A Tompkins, RG Toner, M TI Effect of flow and surface conditions on human lymphocyte isolation using microfluidic chambers SO LANGMUIR LA English DT Article ID MEMORY B-CELLS; PROTEIN ADSORPTION; PERIPHERAL-BLOOD; OXIDE SURFACES; SEPARATION; MONOLAYERS; FRACTIONATION; CYTOMETER; COATINGS; SYSTEM AB Phenotypically pure subpopulations of lymphocytes can provide valuable insights into the immune response to injury and disease. The isolation of these subpopulations presents unique challenges, particularly when preprocessing incubation to attach fluorescent or antibody tags is to be minimized. This paper examines the separation of T and B lymphocytes from mixtures using microfluidic chambers coated with antibodies, focusing on flow conditions and surface chemistry. The adhesion of both cell types decreases as shear stress increases irrespective of the surface chemistry. The incorporation of poly(ethylene glycol) chains along with the antibodies on the chamber surface is shown to significantly improve the reproducibility of cell adhesion and is thus an important part of the overall system design. Furthermore, this technique is shown to be an effective way of isolating highly pure subpopulations of lymphocytes from model mixtures, even when the target cell concentration is low. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org FU NIBIB NIH HHS [P41 EB002503]; NIGMS NIH HHS [U54 GM062119] NR 28 TC 101 Z9 105 U1 2 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD DEC 21 PY 2004 VL 20 IS 26 BP 11649 EP 11655 DI 10.1021/la048047b PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 880VC UT WOS:000225816800051 PM 15595794 ER PT J AU Wong, SH Santambrogio, L Strominger, JL AF Wong, SH Santambrogio, L Strominger, JL TI Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen presentation; endosomes; LPS; nitric oxide synthetase; protease inhibitors ID ANTIGEN PRESENTATION; ERYTHROID-DIFFERENTIATION; IMMUNE-SYSTEM; S-NITROSATION; T-CELLS; ACTIVATION; APOPTOSIS; CHAIN; ENDOCYTOSIS; TRANSPORT AB The passage of dendritic cells (DC) from immature to terminally differentiated antigen-presenting cells is accompanied by numerous morphological, phenotypic, and functional changes. These changes include, for example, expression of "empty" class II MHC proteins (MHCII) at the surface in immature DC, whereas a much larger amount of peptide-loaded MHCII is expressed at the surface in mature DC. Here we show that, in cultured immature DC derived from murine bone-marrow precursors, a number of molecules involved in intracellular trafficking were present in a cleaved form, degraded by caspase-like proteases. Cleavage was either inhibited or reduced significantly during maturation of DC induced by either LPS and TNF-alpha or by peptides that inhibit caspase activities. Inducible nitric oxide (NO) synthetase up-regulated by LPS was essential for inhibiting the caspase-like activity during the maturation of DC. Moreover, treatment with LPS or caspase inhibitor resulted in expression of MHCII/peptide complexes at the cell surface. Thus, the alteration of the endosomal trafficking pathways during the development of DC that parallels the changes in surface expression of MHCII is regulated at least in part by the activities of caspases, inducible NO synthetase, and its product NO. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Strominger, JL (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM jlstrom@fas.harvard.edu FU NCI NIH HHS [CA47554]; NIAID NIH HHS [AI-48832, AI-49524, R01 AI048832, R01 AI049524] NR 45 TC 34 Z9 37 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 2004 VL 101 IS 51 BP 17783 EP 17788 DI 10.1073/pnas.0408229102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PT UT WOS:000225951500040 PM 15598739 ER PT J AU Nishiguchi, KM Friedman, JS Sandberg, MA Swaroop, A Berson, EL Dryja, TP AF Nishiguchi, KM Friedman, JS Sandberg, MA Swaroop, A Berson, EL Dryja, TP TI Recessive NRL mutations in patients with clumped pigmentary retinal degeneration and relative preservation of blue cone function SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cone photoreceptor; retina; retinitis pigmentosa; transcription factor ID TRANSCRIPTION FACTOR NRL; NUCLEAR RECEPTOR NR2E3; DOMINANT RETINITIS-PIGMENTOSA; GOLDMANN-FAVRE-SYNDROME; LEUCINE-ZIPPER; ROD PHOTORECEPTORS; CLINICAL FINDINGS; NIGHT BLINDNESS; SUBUNIT GENE; DOMAIN AB Mice lacking the transcription factor Nrl have no rod photoreceptors and an increased number of short-wavelength-sensitive cones. Missense mutations in NRL are associated with autosomal dominant retinitis pigmentosa; however, the phenotype associated with the loss of NRL function in humans has not been reported. We identified two siblings who carried two allelic mutations: a predicted null allele (L75fs) and a missense mutation (L160P) altering a highly conserved residue in the domain involved in DNA-binding-site recognition. In vitro luciferase reporter assays demonstrated that the NRL-L160P mutant had severely reduced transcriptional activity compared with the WT NRL protein, consistent with a severe loss of function. The affected patients had night blindness since early childhood, consistent with a severe reduction in rod function. Color vision was normal, suggesting the presence of all cone color types; nevertheless, a comparison of central visual fields evaluated with white-on-white and blue-on-yellow light stimuli was consistent with a relatively enhanced function of short-wavelength-sensitive cones in the macula. The fundi had signs of retinal degeneration (such as vascular attenuation) and clusters of large, clumped, pigment deposits in the peripheral fundus at the level of the retinal pigment epithelium (clumped pigmentary retinal degeneration). Our report presents an unusual clinical phenotype in humans with loss-of-function mutations in NRL. C1 Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Ophthalmol, Ann Arbor, MI 48105 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Visual Sci, Ann Arbor, MI 48105 USA. Univ Michigan, WK Kellogg Eye Ctr, Dept Human Genet, Ann Arbor, MI 48105 USA. RP Dryja, TP (reprint author), Ocular Mol Genet Inst, Boston, MA 02114 USA. EM thaddeus_dryja@meei.harvard.edu OI Swaroop, Anand/0000-0002-1975-1141 FU NEI NIH HHS [EY08683, EY11115, R01 EY000169, EY00169, R01 EY008683, R01 EY011115, R37 EY000169] NR 40 TC 47 Z9 49 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 21 PY 2004 VL 101 IS 51 BP 17819 EP 17824 DI 10.1073/pnas.0408183101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 882PT UT WOS:000225951500046 PM 15591106 ER PT J AU Fan, HX Nicholls, J Chua, D Chan, KH Sham, J Lee, S Gulley, ML AF Fan, HX Nicholls, J Chua, D Chan, KH Sham, J Lee, S Gulley, ML TI Laboratory markers of tumor burden in nasopharyngeal carcinoma: A comparison of viral load and serologic tests for Epstein-Barr virus SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Epstein-Barr virus; viral load; serology; nasopharyngeal carcinoma; tumor marker ID BLOOD-PROCESSING PROTOCOLS; CIRCULATING EBV DNA; QUANTITATIVE-ANALYSIS; NPC PATIENTS; PLASMA; ANTIBODY; PROTEIN; QUANTIFICATION; DIAGNOSIS; INFECTION AB Epstein-Barr virus (EBV) is present within the tumor cells of most cases of nasopharyngeal carcinoma (NPC). Recent studies suggest that tumor burden is proportional to the level of EBV DNA in blood and that rapid blood testing can be used to guide therapeutic intervention. The relative utility of viral load vs. serology has been insufficiently studied. In our study, EBV viral load was measured by quantitative PCR using either real-time or end-point detection systems in serum samples from 124 NPC patients (93 pretreatment, 13 relapsed, 18 in remission) and 40 controls. Serologic titers against EBV early antigen were measured in the same serum samples. EBV DNA was detectable in 64 of 93 untreated NPC patients (69%; mean viral load 11,211 copies/ml), 11 of 13 relapsed NPC patients (85%; mean 53,039 copies/ml) and 0 of 18 remission patients. EBV DNA was detectable in only 1 of 40 non-NPC controls (3%). In 34 instances where paired plasma and serum samples were available for testing, both were effective sample types, and there was no significant difference between end-point and real-time methods for measuring viral load. Early antigen (EA) IgA and IgG titers were elevated in most NPC patients regardless of whether their disease was active or in remission. EBV viral load was more informative than was EA serology for distinguishing remission from relapsed disease. EBV DNA measurement appears to be a noninvasive way to monitor tumor burden after therapy. (C) 2004 Wiley-Liss, Inc. C1 Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Gulley, ML (reprint author), Univ N Carolina, Dept Pathol, Brinkhous Bullitt Bldg, Chapel Hill, NC 27599 USA. EM margaret_gulley@med.unc.edu NR 47 TC 39 Z9 42 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 20 PY 2004 VL 112 IS 6 BP 1036 EP 1041 DI 10.1002/ijc.20520 PG 6 WC Oncology SC Oncology GA 870SJ UT WOS:000225077900017 PM 15386346 ER PT J AU Kuznetsov, SA Riminucci, M Ziran, N Tsutsui, TW Corsi, A Calvi, L Kronenberg, HM Schipani, E Robey, PG Bianco, P AF Kuznetsov, SA Riminucci, M Ziran, N Tsutsui, TW Corsi, A Calvi, L Kronenberg, HM Schipani, E Robey, PG Bianco, P TI The interplay of osteogenesis and hematopoiesis: expression of a constitutively active PTH/PTHrP receptor in osteogenic cells perturbs the establishment of hematopoiesis in bone and of skeletal stem cells in the bone marrow SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; FIBROUS DYSPLASIA; IN-VIVO; METAPHYSEAL CHONDRODYSPLASIA; STROMAL FIBROBLASTS; GRAFT SUBSTITUTES; LOCALIZATION; MICE; PRECURSORS AB The ontogeny of bone marrow and its stromal compartment, which Is generated from skeletal stem/ progenitor cells, was investigated in vivo and ex vivo in mice expressing constitutively active parathyroid hormone/paratkyroid hormone-related peptide receptor (PTH/PTHrP; caPPR) under the control of the 2.3-kb bone-specific mouse Col1A1 promoter/enhancer. The transgene promoted increased bone formation within prospective marrow space, but delayed the transition from bone to bone marrow during growth, the formation of marrow cavities, and the appearance of stromal cell types such as marrow adipocytes and cells supporting hematopoiesis. This phenotype resolved spontaneously over time, leading to the establishment of marrow containing a greatly reduced number of clonogenic stromal cells. Proliferative osteoprogenitors, but not multipotent skeletal stem cells (mesenchymal stem cells), capable of generating a complete heterotopic bone organ upon in vivo transplantation were assayable in the bone marrow of caPPR mice. Thus, PTH/PTHrP signaling is a major regulator of the ontogeny of the bone marrow and its stromal tissue, and of the skeletal stem cell compartment. C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Aquila, Dipartimento Med Sperimentale, I-67010 Coppito, Italy. Parco Sci Biomed San Raffaele, I-00161 Rome, Italy. Univ Rome La Sapienza 3, Dipartimento Med Sperimentale & Pathol, I-00161 Rome, Italy. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Robey, PG (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. EM probey@dir.nidcr.nih.gov; p.bianco@flashnet.it RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Calvi, Laura Maria/0000-0001-6969-239X FU NIAMS NIH HHS [P50 AR044855, AR044855]; NIDCR NIH HHS [Z01 DE000380, Z01 DE00380-20]; NIDDK NIH HHS [K08 DK064381, K08 DK064381-02, R21 DK069563, R21 DK069563-01]; Telethon [E.1029] NR 42 TC 78 Z9 80 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1113 EP 1122 DI 10.1083/jcb.200408079 PG 10 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800012 PM 15611335 ER PT J AU Yang, XW Kovalenko, OV Tang, W Claas, C Stipp, CS Hemler, ME AF Yang, XW Kovalenko, OV Tang, W Claas, C Stipp, CS Hemler, ME TI Palmitoylation supports assembly and function of integrin-tetraspanin complexes SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; PHOSPHOINOSITIDE 3-OH KINASE; EPITHELIAL-CELL MIGRATION; ALPHA-3-BETA-1 INTEGRIN; ALPHA-6-BETA-4 INTEGRIN; LIPID RAFTS; ALPHA(6)BETA(4) INTEGRIN; CARCINOMA INVASION; BETA(1) INTEGRINS; FATTY ACYLATION AB As observed previously, tetraspanin palmitoylation promotes tetraspanin microdomain assembly. Here, we show that palmitoylated integrins (alpha3, alpha6, and beta4 subunits) and tetraspanins (CD9, CD81, and CD63) coexist in substantially overlapping complexes. Removal of beta4 palmitoylation sites markedly impaired cell spreading and signaling through pl30Cas on laminin substrate. Also in palmitoylation-deficient beta4, secondary associations with tetraspanins (CD9, CD81, and CD63) were diminished and cell surface CD9 clustering was decreased, whereas core alpha6beta4-CD151 complex formation was unaltered. There is also a functional connection between CD9 and beta4 integrins, as evidenced by anti-CD9 antibody effects on beta4-dependent cell spreading. Notably, beta4 palmitoylation neither increased localization into "light membrane" fractions of sucrose gradients nor decreased solubility in nonionic detergents-hence it does not promote lipid raft association. instead, pall toylation of beta4 (and of the closely associated tetraspanin CD151) promotes CD151-alpha6beta4 incorporation into a network of secondary tetraspanin interactions (with CD9, CD81, CD63, etc.), which provides a novel framework for functional regulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@dfci.harvard.edu FU NCI NIH HHS [CA42368, CA86712, R01 CA042368, R01 CA086712] NR 58 TC 129 Z9 132 U1 3 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1231 EP 1240 DI 10.1083/jcb.200404100 PG 10 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800022 PM 15611341 ER PT J AU Kim, M Carman, CV Yang, W Salas, A Springer, TA AF Kim, M Carman, CV Yang, W Salas, A Springer, TA TI The primacy of affinity over clustering in regulation of adhesiveness of the integrin alpha(L)beta 2 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; LEUKOCYTE INTEGRIN LFA-1; LIGAND-BINDING; I-DOMAIN; FIBRINOGEN RECEPTOR; ADHESION RECEPTORS; AVIDITY REGULATION; T-LYMPHOCYTES; CELL-ADHESION; ACTIVATION AB Dynamic regulation of integrin adhesiveness is required for immune cell-cell interactions and leukocyte migration. Here, we investigate the relationship between cell adhesion and integrin microclustering as measured by fluorescence resonance energy transfer, and macroclustering as measured by high resolution fluorescence microscopy. Stimuli that activate adhesion through leukocyte function-associated molecule-1 (LFA-1) failed to alter clustering of LFA-1 in the absence of ligand. Binding of monomeric intercellular adhesion molecule-1 (ICAM-1) induced profound changes in the conformation of LFA-1 but did not alter clustering, whereas binding of ICAM-1 oligomers induced significant microclustering. Increased diffusivity in the membrane by cytoskeleton-disrupting agents was sufficient to drive adhesion in the absence of affinity modulation and was associated with a greater accumulation of LFA-1 to the zone of adhesion, but redistribution did not precede cell adhesion. Disruption of conformational communication within the extracellular domain of LFA-1 blocked adhesion stimulated by affinity-modulating agents, but not adhesion stimulated by cytoskeleton-disrupting agents. Thus, LFA-1 clustering does not precede ligand binding, and instead functions in adhesion strengthening after binding to multivalent ligands. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu RI Carman, Christopher/L-8108-2016; OI Carman, Christopher/0000-0001-7358-2548; Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [R01 CA031798, R37 CA031798]; PHS HHS [C31798] NR 47 TC 159 Z9 166 U1 3 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 20 PY 2004 VL 167 IS 6 BP 1241 EP 1253 DI 10.1083/jcb.200404160 PG 13 WC Cell Biology SC Cell Biology GA 883TE UT WOS:000226037800023 PM 15611342 ER PT J AU Bach, JF Bendelac, A Brenner, MB Cantor, H De Libero, G Kronenberg, M Lanier, LL Raulet, DH Shlomchik, MJ von Herrath, MG AF Bach, JF Bendelac, A Brenner, MB Cantor, H De Libero, G Kronenberg, M Lanier, LL Raulet, DH Shlomchik, MJ von Herrath, MG TI The role of innate immunity in autoimmunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID KILLER T-CELLS; NATURAL-KILLER; DENDRITIC CELLS; NOD MOUSE; PREVENTS; NKG2D; MICE; SELF; INTERLEUKIN-4; ACTIVATION C1 Hop Necker Enfants Malad, INSERM, U580, Paris, France. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland. La Jolla Inst Alleregy & Immunol, San Diego, CA USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Canc Res, San Francisco, CA 94143 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. NR 28 TC 28 Z9 28 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 20 PY 2004 VL 200 IS 12 BP 1527 EP 1531 DI 10.1084/jem.20042110 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 883QL UT WOS:000226030700001 PM 15611284 ER PT J AU Timm, J Lauer, GM Kavanagh, DG Sheridan, I Kim, AY Lucas, M Pillay, T Ouchi, K Reyor, LL zur Wiesch, JS Gandhi, RT Chung, RT Bhardwaj, N Klenerman, P Walker, BD Allen, TM AF Timm, J Lauer, GM Kavanagh, DG Sheridan, I Kim, AY Lucas, M Pillay, T Ouchi, K Reyor, LL zur Wiesch, JS Gandhi, RT Chung, RT Bhardwaj, N Klenerman, P Walker, BD Allen, TM TI CD8 epitope escape and reversion in acute HCV infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE HLA footprint; processing mutation; viral evolution; acute hepatitis C; CD8 escape ID HEPATITIS-C VIRUS; CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; PERIPHERAL-BLOOD; TYPE-1 INFECTION; QUANTITATIVE-ANALYSIS; VIRAL CLEARANCE; DENDRITIC CELLS; HLA-B; SELECTION AB In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8(+) cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8(+) T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Gastrointestinal Unit, Boston, MA 02114 USA. Univ Oxford, Nuffield Dept Clin Med, Oxford OX1 3SY, England. NYU, Sch Med, New York, NY 10016 USA. RP Allen, TM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Gastrointestinal Unit, Bldg 149,139th St,Rm 6618 B, Boston, MA 02114 USA. EM tallen2@partners.org RI Yang, Chen/G-1379-2010; Allen, Todd/F-5473-2011 FU NIAID NIH HHS [AI31563, R01 AI031563] NR 52 TC 204 Z9 209 U1 1 U2 9 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 DEC 20 PY 2004 VL 200 IS 12 BP 1593 EP 1604 DI 10.1084/jem.20041006 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 883QL UT WOS:000226030700008 PM 15611288 ER PT J AU Valencia, X Higgins, JMG Kiener, HP Lee, DM Podrebarac, TA Dascher, CC Watts, GFM Mizoguchi, E Simmons, B Patel, DD Bhan, AK Brenner, MB AF Valencia, X Higgins, JMG Kiener, HP Lee, DM Podrebarac, TA Dascher, CC Watts, GFM Mizoguchi, E Simmons, B Patel, DD Bhan, AK Brenner, MB TI Cadherin-11 provides specific cellular adhesion between fibroblast-like synoviocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE synovium; synoviocyte; rheumatoid arthritis; cadherin; cell adhesion ID RHEUMATOID-ARTHRITIS; SYNOVIAL FIBROBLAST; EXPRESSION; CANCER; MORPHOGENESIS; ASSOCIATION; PHENOTYPE; CARCINOMA; CLONING; CELLS AB Cadherins are integral membrane proteins expressed in tissue-restricted patterns that mediate homophilic intercellular adhesion. During development, they orchestrate tissue morphogenesis and, in the adult, they determine tissue integrity and architecture. The synovial lining is a condensation of fibroblast-like synoviocytes (FLS) and macrophages one to three cells thick. These cells are embedded within the extracellular matrix, but the structure is neither ail epithelium nor an endothelium. Previously, the basis for organization of the synovium into a tissue was unknown. Here, we cloned cadherin-11 from human rheumatoid arthritis (RA)-derived FLS. We developed L cell transfectants expressing cadherin-11, cadherin-11 fusion proteins, and anti-cadherin-11 mAb. Cadherin-11 was found to be expressed mainly in the synovial lining by immunohistologic staining of human synovium. FLS adhered to cadherin-11-Fc, and transfection of cadherin-11 conferred the formation of tissue-like sheets and lining-like structures upon fibroblasts in vitro. These findings support a key role for cadherin-11 in the specific adhesion of FLS and in synovial tissue organization and behavior in health and RA. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunopathol Unit, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Div Allergy & Immunol, Durham, NC 27710 USA. RP Brenner, MB (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Smith Bldg,Rm 552,1 Jimmy Fund Way, Boston, MA 02115 USA. EM mbrenner@rics.bwh.harvard.edu FU NIAMS NIH HHS [AR48114, AR02214, K08 AR002214, R01 AR048114]; NIDDK NIH HHS [DK47677, DK43351, P30 DK043351, R01 DK047677] NR 29 TC 78 Z9 82 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 DEC 20 PY 2004 VL 200 IS 12 BP 1673 EP 1679 DI 10.1084/jem.20041545 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 883QL UT WOS:000226030700016 PM 15611293 ER PT J AU Ripoll, J Ntziachristos, V AF Ripoll, J Ntziachristos, V TI Imaging scattering media from a distance: Theory and applications of noncontact optical tomography SO MODERN PHYSICS LETTERS B LA English DT Review DE diffuse optical tomography; noncontact tomography; imaging in scattering media; radiative transfer equation; diffusion ID PHOTON DENSITY WAVES; FLUORESCENCE MOLECULAR TOMOGRAPHY; TIME-RESOLVED REFLECTANCE; SINGULAR-VALUE ANALYSIS; IN-VIVO; TURBID MEDIA; BOUNDARY-CONDITIONS; DIFFUSION EQUATION; OXYGEN-SATURATION; INDOCYANINE GREEN AB Optical tomography of turbid media has been largely limited to systems that require fixed geometries or measurements employing fibers. Noncontact optical measurements from diffuse media could facilitate the use of large detector arrays at multiple angles that are well-suited for tomography applications. Such imaging strategies eliminate the need for individual fibers in contact with the highly scattering volume, the use of restricted geometries and the need for matching fluids. Here we review the different approaches and systems developed for noncontact optical measurements and concurrent registration of the three-dimensional surface information of the diffuse medium. We present the basic theoretical formulation and its experimental validation, finally applying it to the specific case of fluorescence tomography of small animals. We discuss how these new technologies can considerably simplify experimental procedures and improve our ability to visualize functional and molecular processes in vivo. Future perspectives and work are also outlined. C1 Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Boston, MA 02115 USA. RP Ripoll, J (reprint author), Fdn Res & Technol Hellas, Inst Elect Struct & Laser, POB 1527, Iraklion 71110, Greece. EM jripoll@iesl.forth.gr; vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 87 TC 39 Z9 40 U1 1 U2 8 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0217-9849 J9 MOD PHYS LETT B JI Mod. Phys. Lett. B PD DEC 20 PY 2004 VL 18 IS 28-29 BP 1403 EP 1431 DI 10.1142/S0217984904007864 PG 29 WC Physics, Applied; Physics, Condensed Matter; Physics, Mathematical SC Physics GA 896AA UT WOS:000226905700001 ER PT J AU del Re, E Sidis, Y Fabrizio, DA Lin, HY Schneyer, A AF del Re, E Sidis, Y Fabrizio, DA Lin, HY Schneyer, A TI Reconstitution and analysis of soluble inhibin and activin receptor complexes in a cell-free system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXTRACELLULAR DOMAIN; EXPRESSION CLONING; SIGNALING PATHWAY; SERINE KINASE; III RECEPTOR; BINDING; BETA; GROWTH; FOLLISTATIN; PROTEIN AB Activins and inhibins compose a heterogeneous subfamily within the transforming growth factor-beta (TGF-beta) superfamily of growth and differentiation factors with critical biological activities in embryos and adults. They signal through a heteromeric complex of type II, type I, and for inhibin, type III receptors. To characterize the affinity, specificity, and activity of these receptors (alone and in combination) for the inhibin/ activin subfamily, we developed a cell-free assay system using soluble receptor-Fc fusion proteins. The soluble activin type II receptor (sActRII)-Fc fusion protein had a 7-fold higher affinity for activin A compared with sActRIIB-Fc, whereas both receptors had a marked preference for activin A over activin B. Although inhibin A and B binding was 20-fold lower compared with activin binding to either type II receptor alone, the mixture of either type II receptor with soluble TGF-beta type III receptor (TbetaRIII; betaglycan)-Fc reconstituted a soluble high affinity inhibin receptor. In contrast, mixing either soluble activin type II receptor with soluble activin type I receptors did not substantially enhance activin binding. Our results support a cooperative model of binding for the inhibin receptor (ActRII.sTbetaRIII complex) but not for activin receptors (type II + type I) and demonstrate that a complex composed of activin type II receptors and TbetaRIII is both necessary and sufficient for high affinity inhibin binding. This study also illustrates the utility of this cell-free system for investigating hypotheses of receptor complex mechanisms resulting from crystal structure analyses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02114 USA. RP Schneyer, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM schneyer.alan@mgh.harvard.edu NR 43 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53126 EP 53135 DI 10.1074/jbc.M408090200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600041 PM 15475360 ER PT J AU Arnett, HA Fancy, SPJ Alberta, JA Zhao, C Plant, SR Kaing, S Raine, CS Rowitch, DH Franklin, RJM Stiles, CD AF Arnett, HA Fancy, SPJ Alberta, JA Zhao, C Plant, SR Kaing, S Raine, CS Rowitch, DH Franklin, RJM Stiles, CD TI bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS SO SCIENCE LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; MULTIPLE-SCLEROSIS LESIONS; CENTRAL-NERVOUS-SYSTEM; ETHIDIUM-BROMIDE; ADULT CNS; REMYELINATION; EXPRESSION AB Olig1 and Olig2 are closely related basic helix-loop-helix (bHLH) transcription factors that are expressed in myelinating oligodendrocytes and their progenitor cells in the developing central nervous system (CNS). Olig2 is necessary for the specification of oligodendrocytes, but the biological functions of Otig1 during oligodendrocyte lineage development are poorly understood. We show here that Olig1 function in mice is required not to develop the brain but to repair it. Specifically, we demonstrate a genetic requirement for Olig1 in repairing the types of lesions that occur in patients with multiple sclerosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB3 0ES, England. Univ Cambridge, Dept Vet Med, Cambridge CB3 0ES, England. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Albert Einstein Coll Med, Dept Pathol Neuropathol, Bronx, NY 10461 USA. RP Franklin, RJM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM rjf1000@cam.ac.uk; charles-stiles@dfci.harvard.edu RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU Multiple Sclerosis Society [689]; NINDS NIH HHS [NS08952, NS11920, NS4051] NR 28 TC 259 Z9 272 U1 2 U2 6 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 DEC 17 PY 2004 VL 306 IS 5704 BP 2111 EP 2115 DI 10.1126/science.1103709 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 881CM UT WOS:000225841000068 PM 15604411 ER PT J AU Richardson, PG Kassarjian, A Jing, W AF Richardson, PG Kassarjian, A Jing, W TI A 40-year-old man with a large tumor of the skull - Plasma-cell myeloma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROTEASOME INHIBITOR PS-341; UNTREATED MULTIPLE-MYELOMA; OVERCOMES DRUG-RESISTANCE; HIGH-DOSE CHEMOTHERAPY; STAGING SYSTEM; THALIDOMIDE; DEXAMETHASONE; TRANSPLANTATION; THERAPY; PHASE-2 C1 Brigham & Womens Hosp, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Richardson, PG (reprint author), Brigham & Womens Hosp, Jerome Lipper Multiple Myeloma Ctr, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. NR 40 TC 5 Z9 5 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 DEC 16 PY 2004 VL 351 IS 25 BP 2637 EP 2645 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 879OC UT WOS:000225726100013 PM 15602025 ER PT J AU Greene, MF AF Greene, MF TI Vaginal birth after cesarean revisited SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONTROLLED-TRIALS; DELIVERY; LABOR; RISK C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 10 TC 21 Z9 21 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 DEC 16 PY 2004 VL 351 IS 25 BP 2647 EP 2649 DI 10.1056/NEJMe048277 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 879OC UT WOS:000225726100014 PM 15598961 ER PT J AU Khachemoune, A Ogholikhan, M AF Khachemoune, A Ogholikhan, M TI Whitish papules and plaques on the tongue SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Khachemoune, A (reprint author), Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD DEC 15 PY 2004 VL 70 IS 12 BP 2353 EP 2354 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 880IA UT WOS:000225781000011 PM 15617301 ER PT J AU Karha, J Gibson, CM Murphy, SA DiBattiste, PM Cannon, CP AF Karha, J Gibson, CM Murphy, SA DiBattiste, PM Cannon, CP CA TIMI Study Grp TI Safety of stress testing during the evolution of unstable angina pectoris or non-ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONSERVATIVE STRATEGIES; EXERCISE; TRIAL AB Patients (n = 1,106) were chosen from the conservative arm of the Treat Angina with aggrastat and determine cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI) 18 trial. Only 1 patient had a myocardial infarction and another died on the day of stress testing (mortality 0.12%). In patients with unstable angina pectoris or non-ST-elevation myocardial infarction treated with aspirin, heparin, and tirofiban, performance of an exercise or a pharmacologic stress test in selected patients within 48 to 72 hours after admission appears to be associated with a low risk of complications. (C) 2004 by Excerpta Medica Inc. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. Merck & Co Inc, W Point, PA USA. RP Karha, J (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Desk F-15,9500 Euclid Ave, Cleveland, OH 44195 USA. EM karhaj@ccf.org NR 11 TC 4 Z9 4 U1 0 U2 1 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 DEC 15 PY 2004 VL 94 IS 12 BP 1537 EP 1539 DI 10.1016/j.amjcard.2004.08.033 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 880IF UT WOS:000225781500012 PM 15589011 ER PT J AU Jackson, SL Boyko, EJ Scholes, D Abraham, L Gupta, K Fihn, SD AF Jackson, SL Boyko, EJ Scholes, D Abraham, L Gupta, K Fihn, SD TI Predictors of urinary tract infection after menopause: A prospective study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; RISK-FACTORS; DIABETES-MELLITUS; ASYMPTOMATIC BACTERIURIA; ESCHERICHIA-COLI; YOUNG-WOMEN; PREVALENCE AB PURPOSE: To describe the incidence of and risk factors for acute cystitis among nondiabetic and diabetic postmenopausal women. METHODS: We conducted a population-based, prospective cohort study of 1017 postmenopausal women, aged 55 to 75 years, who were enrolled in a health maintenance organization and followed for 2 years. A wide range of behavioral and physiologic exposures were assessed at baseline interview and follow-up clinic visits; the main outcome measure was microbiologically-confirmed acute symptomatic cystitis. Follow-up was 87% at 12 months and 81% at 24 months. RESULTS: During 1773 person-years of follow-up, 138 symptomatic urinary tract infections occurred (incidence, 0.07 per person-year). Independent predictors of infection included insulin-treated diabetes (hazard ratio [HR] = 3.4; 95% confidence interval [CI]: 1.7 to 7.0) and a lifetime history of Urinary tract infection (HR for six or more infections = 6.9; 95% CI: 3.5 to 13.6). Borderline associations included a history of vaginal estrogen cream use in the last month (HR = 1.3; 95% CI: 1.0 to 3.4), a history of kidney stories (HR = 1.9; 95% CI: 1.0 to 3.7), and asymptomatic bacteriuria at baseline (HR = 1.8, 95% CI: 0.9 to 3.5). Sexual activity, urinary incontinence, parity, postcoital urination, vaginal dryness, use of cranberry juice, vaginal bacterial flora, and postvoid residual bladder volume were not associated with incident acute cystitis after multivariable adjustment. CONCLUSION: Insulin-treated diabetes is a potentially modifiable risk factor for incident acute cystitis among postmenopausal women, whereas a lifetime history of urinary tract infection was the strongest predictor. Use of oral or vaginal estrogen was not protective, and a wide range of behavioral and physiologic factors was not associated with acute cystitis episodes in this generally healthy sample. (C) 2004 by Elsevier Inc. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98103 USA. NW Hlth Serv Res & Dev Program, Seattle, WA 98103 USA. Epidemiol Res & Informat Ctr, Seattle, WA 98103 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Yale Univ, Dept Med Infect Dis, West Haven, CT USA. RP Jackson, SL (reprint author), VA Puget Sound Hlth Care Syst, 1825 N 52nd St, Seattle, WA 98103 USA. EM sljack@u.washington.edu FU NIDDK NIH HHS [DK02660, DK43134] NR 32 TC 57 Z9 59 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2004 VL 117 IS 12 BP 903 EP 911 DI 10.1016/j.amjmed.2004.07.045 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 884SL UT WOS:000226106300002 PM 15629728 ER PT J AU Solomon, DH Brookhart, MA Gandhi, TK Karson, A Gharib, S Orav, EJ Shaykevich, S Licari, A Cabral, D Bates, DW AF Solomon, DH Brookhart, MA Gandhi, TK Karson, A Gharib, S Orav, EJ Shaykevich, S Licari, A Cabral, D Bates, DW TI Adherence with osteoporosis practice guidelines: A multilevel analysis of patient, physician, and practice setting characteristics SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; ELDERLY-PATIENTS; HIP FRACTURE; OPPORTUNITY; CARE; PREVENTION; MANAGEMENT; PATTERNS; RATES AB PURPOSE: The diagnosis and treatment of patients at risk of fragility fractures is uncommon. We examined the patient, physician, and practice characteristics associated with adherence to local osteoporosis guidelines. METHODS: Data were obtained from electronic medical records from one academic medical center. Local guidelines suggest screening and consideration of treatment for at-risk patients, including women aged greater than or equal to 65 years, women aged 50 to 64 years who smoke cigarettes, persons who used more than 5 mg of oral prednisone for > 3 months, and those with a history of a fracture after age 45 years. Clinical notes, medication lists, and radiology records were reviewed to determine whether patients had undergone bone mineral density testing or received any medications for osteoporosis. Possible correlates of guideline adherence, including patient, physician, and practice site characteristics, were assessed in mixed multivariable models. RESULTS: We identified 6311 at-risk patients seen by 160 doctors at 10 primary care sites during 2001 to 2002. Of these patients, 45% (n = 2820) had a prior bone mineral density test and 30% (n = 1922) had received a medication for osteoporosis; 54%(n = 3401) had one or the other. After adjusting for patient case mix, 17% to 71% of patients had been managed according to local guidelines and had undergone at least bone mineral density testing or received a medication. Patient variables that significantly lowered the probability of guideline adherence included age > 74 years (odds ratio [OR] = 0.49; 95% confidence interval [CI]: 0.43 to 0.55), age < 55 years (OR = 0.34; 95% CI: 0.28 to 0.42), male sex (OR 0.17; 95% CI: 0.12 to 0.23), black race (OR = 0.40; 95% CI: 0.34 to 0.47), and having more than one comorbid condition (OR = 0.79; 95% CI: 0.69 to 0.89). Patients seen by male physicians were less likely to have care that was adherent with guidelines (OR = 0.70; 95% CI: 0.55 to 0.89). CONCLUSION: Rates of adherence with local osteoporosis guidelines for patients at risk of fragility fractures vary by patient, physician, and practice site characieristic. (C) 2004 by Elsevier Inc. C1 Brigham & Womens Hosp, Div Rheumatol, Div Pharmacoepidemiol, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Med Unit, Boston, MA USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Rheumatol, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org FU AHRQ HHS [HS11046]; NIAMS NIH HHS [AR48264, AR48616] NR 15 TC 71 Z9 72 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2004 VL 117 IS 12 BP 919 EP 924 DI 10.1016/j.amjmed.2004.06.040 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 884SL UT WOS:000226106300004 PM 15629730 ER PT J AU Au, DH Bryson, CL Fan, VS Udris, EM Curtis, JR McDonell, MB Fihn, SD AF Au, DH Bryson, CL Fan, VS Udris, EM Curtis, JR McDonell, MB Fihn, SD TI Beta-blockers as single-agent therapy for hypertension and the risk of mortality among patients with chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PHARMACY RECORDS; HEALTH; VALIDATION; VALIDITY; SMOKING; DECLINE; ASTHMA; TRIAL AB PURPOSE: To assess the association between the type of antihypertensive medication and all-cause mortality among patients with chronic obstructive pulmonary disease (COPD). METHODS: The cohort comprised 1.966 patients (mean [ +/- SD] age, 65.8 +/- 10.7 years) enrolled in general internal medicine clinics at seven Veterans Affairs medical centers between December 1996 and October 1999. Patients had a diagnosis of both COPD and hypertension and were receiving single-agent antihypertensive therapy. RESULTS: Compared with calcium channel blockers, beta-blockers were associated with a decrease in mortality from any cause after adjusting for propensity for having been prescribed a beta-blocker (hazard ratio = 0.57; 95% confidence interval: 0.33 to 0.89). The association was similar when beta-blockers were compared with all other antihypertensive medications and the decreased risk of mortality was apparent among patients with pre-existing cardiac disease. Restriction of analyses to long-acting calcium channel blockers or to patients who used beta-agonists did not affect the point estimates. Exposure to the remaining classes of antihypertensive agents was not associated with mortality. CONCLUSION: Beta-blockers may have beneficial effects in patients who have COPD, pre-existing cardiac disease, and hyper-tension. Beta-blockers may not be contraindicated among patients with COPD. (C) 2004 by Elsevier Inc. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, NW Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Au, DH (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, NW Ctr Excellence, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dau@u.washington.edu NR 19 TC 33 Z9 36 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2004 VL 117 IS 12 BP 925 EP 931 DI 10.1016/j.amjmed.2004.07.043 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 884SL UT WOS:000226106300005 PM 15629731 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, RP Braunwald, E TI Baseline troponin in acute coronary syndromes managed invasively SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID ST-SEGMENT-ELEVATION; TIMI RISK SCORE; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; ARTERY DISEASE; STRATIFICATION; TIROFIBAN; INTERVENTIONS; PERFORMANCE; EFFICACY C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2004 VL 117 IS 12 BP 963 EP 965 DI 10.1016/j.amjmed.2004.11.002 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 884SL UT WOS:000226106300012 PM 15629738 ER PT J AU Choi, HK Curhan, G AF Choi, HK Curhan, G TI Beer, liquor, and wine consumption and serum uric acid level: The Third National Health and Nutrition Examination Survey SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE uric acid; gout; beer; liquor; wine; alcohol; NHANES III ID FOOD-FREQUENCY QUESTIONNAIRE; ADENINE-NUCLEOTIDE TURNOVER; CORONARY HEART-DISEASE; ALCOHOL-CONSUMPTION; GOUT; MEN; DRINKING; RISK; REPRODUCIBILITY; HYPERURICEMIA AB Objective. To evaluate the relationship between intakes of beer, liquor, and wine and serum uric acid levels in a nationally representative sample of men and women. Methods. Using data from 14,809 participants (6,932 men and 7,877 women) age ? 20 years in The Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between intakes of beer, liquor, and wine and serum uric acid levels. Alcohol intake was assessed by a food frequency questionnaire. Results. Serum uric acid levels increased with increasing beer or liquor intake but not with increasing wine intake. After adjusting for age, the difference in serum uric acid levels as compared with no intake increased with increasing beer or liquor intake (P values for trend < 0.001), but the association was inverse with increasing wine intake (P for trend < 0.001). After adjusting mutually for these alcoholic beverages and for other risk factors for hyperuricemia, including dietary risk factors, the associations were attenuated but remained significant for beer or liquor (multivariate difference per serving per day 0.46 mg/dl [95% confidence interval {95% CI} 0.32, 0.60] and 0.29 mg/dl [95% CI 0.14, 0.45], respectively; both P values for trend <0.01), but not for wine (0.04 mg/dl [95% CI -0.20, 0.11]; P for trend = 0.6). Conclusion. These data suggest that the effect of individual alcoholic beverages on serum uric acid levels varies substantially: beer confers a larger increase than liquor, whereas moderate wine drinking does not increase serum uric acid levels. C1 Harvard Univ, Rheumatol Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Choi, HK (reprint author), Harvard Univ, Rheumatol Unit, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM hchoi@partners.org NR 27 TC 105 Z9 114 U1 1 U2 11 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 DEC 15 PY 2004 VL 51 IS 6 BP 1023 EP 1029 DI 10.1002/art.20821 PG 7 WC Rheumatology SC Rheumatology GA 882FA UT WOS:000225923200023 PM 15593346 ER PT J AU Cannistraro, PA Wright, CI Wedig, MM Martis, B Shin, LM Wilhelm, S Rauch, SL AF Cannistraro, PA Wright, CI Wedig, MM Martis, B Shin, LM Wilhelm, S Rauch, SL TI Amygdala responses to human faces in obsessive-compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE functional MRI; limbic system; anxiety disorders; neuroimaging; facial expressions ID GLUCOSE METABOLIC RATES; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; SYMPTOM PROVOCATION; HUMAN BRAIN; PREFRONTAL CORTEX; ANXIETY; ACTIVATION; SCALE; FMRI AB Background: To assess the amygdala response to emotional faces in obsessive-compulsive disorder (OCD) using functional magnetic resonance imaging (fMRI). Methods. Ten subjects with current OCD and 10 healthy control subjects underwent fMRI, during which they viewed pictures of fearful, happy, and neutral human faces, as well as a fixation cross. Results: Across both groups, there was significant activation in left and right amygdala for the fearful versus neutral faces contrast. Data extracted from these functionally defined regions of interest indicated that OCD subjects exhibited a weaker response than control subjects bilaterally across all face conditions versus fixation. No group-by-face condition interactions were observed. Conclusions: Contrary to findings in other anxiety disorders, there was no observed increase in amygdala responsivity to fearful versus neutral human faces in OCD as compared with healthy control subjects. Moreover, across all face conditions, amygdala responsivity was attenuated in OCD subjects relative to control subjects. Therefore, the present findings are consistent with abnormal amygdala function in OCD and are of a character that may distinguish OCD from other anxiety disorders, C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Dept Psychiat, Boston, MA 02129 USA. Massachusetts Gen Hosp, Obsess Compuls Disorders Program, Dept Psychiat, Boston, MA 02129 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol Grp, Boston, MA 02115 USA. VA Healthcare Syst, Dept Psychiat, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Dept Psychiat, Bldg 149,13th St, Boston, MA 02129 USA. EM rauch@psych.mgh.harvard.edu FU NIMH NIH HHS [MH 60219] NR 40 TC 55 Z9 56 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2004 VL 56 IS 12 BP 916 EP 920 DI 10.1016/j.biopsych.2004.09.029 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 883BH UT WOS:000225984500002 PM 15601600 ER PT J AU Manoach, DS Cain, MS Vangel, MG Khurana, A Goff, DC Stickgold, R AF Manoach, DS Cain, MS Vangel, MG Khurana, A Goff, DC Stickgold, R TI A failure of sleep-dependent procedural learning in chronic, medicated schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE cognition; motor skill; procedural learning; schizophrenia; sleep ID WORKING-MEMORY PERFORMANCE; PREFRONTAL CORTEX; NAIVE PATIENTS; BASAL GANGLIA; DELTA SLEEP; REM-SLEEP; SKILL; IMPROVEMENT; IMPAIRMENT; ACTIVATION AB Background: Schizophrenia patients have difficulty studies demonstrate intact procedural learning in schizophrenia, recent findings demonstrate that a critical component of procedural learning is dependent on sleep. This study tested the hypothesis that patients with schizophrenia have a deficit in sleep-dependent procedural learning. Methods: Using a simple, well-characterized test of motor skill learning, the finger tapping motor sequence task (MST), 26 patients with chronic, medicated schizophrenia and 14 demographically matched healthy control subjects were tested on two occasions, 24 hours apart. The main outcome measures were learning of the MST on day 1 (practice-dependent learning) and overnight, sleep-dependent improvement performance. Results: Although schizophrenia patients and control subjects did not differ,fer in practice-dependent learning, patients failed to show overnight improvement (4% deterioration) and differed significantly from control subjects who showed a significant 11% improvement. Conclusions: We present here the first demonstration of a failure of sleep-dependent consolidation of procedural learning in chronic, medicated schizophrenia. This deficit occurred in the context of normal practice-dependent learning within a training session. This behavioral dissociation is consistent with evidence that practice- and sleep-dependent motor learning reflect independent processes and suggests that they are differentially affected in schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp E, 36 1st Ave,Room 420, Boston, MA 02129 USA. EM dara@nmr.mgh.harvard.edu FU NIMH NIH HHS [K23 MH 01829, MH 48832, MH 65492, MH 67754, R01 MH092638] NR 38 TC 60 Z9 60 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2004 VL 56 IS 12 BP 951 EP 956 DI 10.1016/j.bps.2004.09.012 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 883BH UT WOS:000225984500007 PM 15601605 ER PT J AU Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Shivdasani, RA AF Schulze, H Korpal, M Bergmeier, W Italiano, JE Wahl, SM Shivdasani, RA TI Interactions between the megakaryocyte/platelet-specific beta 1 tubulin and the secretory leukocyte protease inhibitor SLPI suggest a role for regulated proteolysis in platelet functions SO BLOOD LA English DT Article ID STABLE PROTEINASE-INHIBITOR; TRANSCRIPTION FACTOR NF-E2; AMINO-ACID-SEQUENCE; BACTERIAL LIPOPOLYSACCHARIDE; ELONGATION FACTOR-1-ALPHA; LEUKOPROTEASE INHIBITOR; ACTIVATED PLATELETS; BLOOD-PLATELETS; DISCOID SHAPE; BINDING-SITE AB Plate let-restricted beta1 tubulin is required for optimal thrombopoiesis and discoid cell shape. To identify interacting factors, we used the divergent beta1-tubulin C-terminus as the bait in a yeast 2-hybrid screen of megakaryocyte (MK) cDNAs. We isolated secretory leukocyte protease inhibitor (SLPI), a serine protease antagonist characterized principally as a secreted factor with multiple roles in inflammation. SLPI is expressed in MKs and platelets in 2 discrete compartments. One pool resides in punctate cytoplasmic structures, whereas a significant fraction localizes along peripheral microtubules (MTs) and is lost with cold-induced MT disruption or in beta1 tubulin(-/-) platelets. These findings reveal unexpected interaction between a prominent cytoskeletal protein and an inhibitor of proteolysis. SLPI-/- mice show intact proplatelet formation, platelet numbers and shape, and marginal MT bands; thus, SLPI is not essential for thrombopoiesis. However, SLPI is released upon platelet activation, which also reverses its association with the resting marginal band. Platelet SLPI inhibits neutrophil elastase, an activity that is reduced when beta1 tubulin is absent. We conclude that SLPI localizes in part along the MK and platelet MT cytoskeleton by virtue of specific interactions with beta1 tubulin. SLPI may thus have unanticipated roles in MK and platelet functions, including regulated proteolysis after activation. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Biomed Res, Ctr Blood Res, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NHLBI NIH HHS [P01HL56949, R01HL63163, R01HL68130] NR 56 TC 19 Z9 20 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2004 VL 104 IS 13 BP 3949 EP 3957 DI 10.1182/blood-2004-03-1179 PG 9 WC Hematology SC Hematology GA 877VC UT WOS:000225601000026 PM 15315966 ER PT J AU Gricks, CS Zahrieh, D Zauls, AJ Gorgon, G Drandi, D Mauerer, K Neuberg, D Gribben, JG AF Gricks, CS Zahrieh, D Zauls, AJ Gorgon, G Drandi, D Mauerer, K Neuberg, D Gribben, JG TI Differential regulation of gene expression following CD40 activation of leukemic compared to healthy B cells SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; ZINC-FINGER PROTEIN; CROSS-LINKING CD40; T-CELLS; INDUCED APOPTOSIS; RECEPTOR; ANTIGEN; IMMUNOTHERAPY; PREDICTION AB It is possible to differentiate malignant from healthy cells and to classify diseases based on identification of specific gene expression profiles. We hypothesized that gene expression profiling could also be used to identify differential activation of healthy and malignant cells, and as a model for this, we examined the molecular sequelae of CD40 activation of healthy and B-cell chronic lymphocytic leukemia (CLL) cells. Hierarchical clustering analysis of gene expression signatures grouped samples by CD40 activation status and further subclassified CD40-activated CLL cells from healthy B cells. Supervised analyses in healthy B cells compared to CLL cells identified differential regulation of genes governing cell cycle progression and apoptosis. CD40 signaling of CLL cells increases their susceptibility to immune recognition, but promotes survival and cell cycle arrest, making these cells potentially more resistant to chemotherapy. These results illustrate the utility of gene expression profiling to elucidate the molecular sequelae of signaling in healthy cells and altered signaling pathways in malignant cells. This type of approach should be useful to identify targets of therapy of malignant diseases. (C) 2004 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Biostat Sci, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med, 44 Binney St,Rm D520, Boston, MA 02115 USA. EM john_gribben@dfci.harvard.edu RI drandi, daniela/Q-6504-2016 FU NCI NIH HHS [CA81534] NR 50 TC 28 Z9 29 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 DEC 15 PY 2004 VL 104 IS 13 BP 4002 EP 4009 DI 10.1182/blood-2004-02-0494 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000033 PM 15161673 ER PT J AU Gauguet, JM Rosen, SD Marth, JD von Andrian, UH AF Gauguet, JM Rosen, SD Marth, JD von Andrian, UH TI Core 2 branching beta 1,6-N-acetylglucosaminyltransferase and high endothelial cell N-acetylglucosamine-6-sulfotransferase exert differential control over B- and T-lymphocyte homing to peripheral lymph nodes SO BLOOD LA English DT Article ID L-SELECTIN LIGAND; SIALYL-LEWIS-X; IN-VIVO; LEUKOCYTE ADHESION; BETA-2 INTEGRINS; PEYERS-PATCHES; DISTINCT ROLES; CAPPING GROUP; VENULES; INFLAMMATION AB Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-1 and high endothelial cell GlcNAc-6-sulfotransferase (HEC-GlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-1(-/-) and HEC-GlcNAc6ST(-/-) mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (V-roll) in C2GlcNAcT-1(-/-) mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST(-/-) HEVs, but V-roll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin(+/-) T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-1 and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anat, Program Immunol, San Francisco, CA 94143 USA. Univ Calif San Diego, Howard Hughes Med Inst, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 200 Longwood Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949]; NIAMS NIH HHS [AR42689]; NIDDK NIH HHS [DK48247]; NIGMS NIH HHS [R01GM57411, R37 GM23547] NR 64 TC 33 Z9 34 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 DEC 15 PY 2004 VL 104 IS 13 BP 4104 EP 4112 DI 10.1182/blood-2004-05-1986 PG 9 WC Hematology SC Hematology GA 877VC UT WOS:000225601000045 PM 15319280 ER PT J AU Raje, N Kumar, S Hideshima, T Ishitsuka, K Chauhan, D Mitsiades, C Podar, K Le Gouill, S Richardson, P Munshi, NC Stirling, DI Antin, JH Anderson, KC AF Raje, N Kumar, S Hideshima, T Ishitsuka, K Chauhan, D Mitsiades, C Podar, K Le Gouill, S Richardson, P Munshi, NC Stirling, DI Antin, JH Anderson, KC TI Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma SO BLOOD LA English DT Article ID GROWTH-FACTOR-I; SIGNAL-TRANSDUCTION PATHWAY; NF-KAPPA-B; INDUCED APOPTOSIS; DRUG-RESISTANCE; CANCER-THERAPY; CELL-GROWTH; ACTIVATION; INTERLEUKIN-6; TARGET AB Previous studies have demonstrated the in vitro and in vivo activity of CC-5013 (Revlimid), an immunomodulatory analog (IMiD) of thalidomide, in multiple myeloma (MM). In the present study, we have examined the anti-MM activity of rapamycin (Rapamune), a specific mTOR inhibitor, combined with CC-5013. Based on the Chou-Talalay method, combination indices of less than 1 were obtained for all dose ranges of CC-5013 when combined with rapamycin, suggesting strong synergism. Importantly, this combination was able to overcome drug resistance when tested against MM cell lines resistant to conventional chemotherapy. Moreover, the combination, but not rapamycin alone, was able to overcome the growth advantage conferred on MM cells by interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), or adherence to bone marrow stromal cells (BMSCs). Combining rapamycin and CC-5013 induced apoptosis of MM cells. Differential signaling cascades, including the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3'-kinase/Akt kinase (PI3K/Akt) pathways, were targeted by these drugs individually and in combination, suggesting the molecular mechanism by which they interfere with MM growth and survival. These studies, therefore, provide the framework for clinical evaluation of mTOR inhibitors combined with IMiDs to improve patient outcome in MM. (C) 2004 by The American Society of Hematology. C1 Dana Farber Canc Inst, VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Celgene Corp, Warren, NJ USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, VA Boston Healthcare Syst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 FU NCI NIH HHS [IP50 CA 10070-01, R0-1 CA 50947]; NHLBI NIH HHS [P01 HL070149-01]; PHS HHS [P0-1 78378] NR 34 TC 127 Z9 131 U1 1 U2 9 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 DEC 15 PY 2004 VL 104 IS 13 BP 4188 EP 4193 DI 10.1182/blood-2004-06-2281 PG 6 WC Hematology SC Hematology GA 877VC UT WOS:000225601000056 PM 15319277 ER PT J AU Yee, KWH Schittenhelm, M O'Farrell, AM Town, AR McGreevey, L Bainbridge, T Cherrington, JM Heinrich, MC AF Yee, KWH Schittenhelm, M O'Farrell, AM Town, AR McGreevey, L Bainbridge, T Cherrington, JM Heinrich, MC TI Synergistic effect of SU11248 with cytarabine or daunorubicin on FLT3 ITD-positive leukemic cells SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; INTERNAL TANDEM DUPLICATION; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; IN-VITRO; BONE-MARROW; MYELOPROLIFERATIVE DISEASE; HEMATOLOGIC MALIGNANCIES AB Fetal liver tyrosine kinase 3 internal tandem duplication (FLT3 ITD) mutations are the most common molecular abnormality associated with adult acute myeloid leukemia (AML). To exploit this molecular target, a number of potent and specific FLT3 kinase inhibitors have been developed and are currently being tested in early phase clinical trials of patients with refractory AML. To explore the efficacy of combining a FLT3 inhibitor with standard AML chemotherapy drugs, we tested the effect of combining the FLT3 inhibitor SU11248 with cytarabine or daunorubicin on the proliferation and survival of cell lines expressing either mutant (FLT3 ITD or FLT3 D835V) or wild-type (WT) FLT3. SU11248 had additive-to-synergistic inhibitory effects on FLT3-dependent leukemic cell proliferation when combined with cytarabine or daunorubicin. The synergistic interaction of SU11248 and the traditional antileukemic agents was more pronounced for induction of apoptosis. SU11248 inhibited the proliferation of primary AML myeloblasts expressing mutant FLT3 ITD but not WT FLT3 protein. Combining SU11248 and cytarabine synergistically inhibited the proliferation of primary AML myeloblasts expressing FLT3 ITD but not WT FLT3 protein. These data suggest that the addition of potent FLT3 inhibitors such as SU11248 to AML chemotherapy regimens could result in improved treatment results. (C) 2004 by The American Society of Hematology. C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Tuebingen, Clin Internal Med, Dept Hematol Oncol Immunol & Rheumatol, Tubingen, Germany. SUGEN, Preclin Res & Exploratory Dev, San Francisco, CA USA. RP Heinrich, MC (reprint author), R&D-19 3710 SW US Vet Affairs Hosp Rd, Portland, OR 97201 USA. EM heinrich@ohsu.edu FU NCI NIH HHS [P30 CA69533] NR 51 TC 79 Z9 79 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 DEC 15 PY 2004 VL 104 IS 13 BP 4202 EP 4209 DI 10.1182/blood-2003-10-3381 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000058 PM 15304385 ER PT J AU Krause, DS Van Etten, RA AF Krause, DS Van Etten, RA TI Adoptive immunotherapy of BCR-ABL-induced chronic myeloid leukemia-like myeloproliferative disease in a murine model SO BLOOD LA English DT Article ID GRAFT-VERSUS-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; PROGENITOR-CELL TRANSPLANTATION; HOST-DISEASE; T-CELLS; ALLOGENEIC CHIMERAS; MICE; TRANSFUSIONS; MALIGNANCY AB Donor leukocyte infusion (DLI) can induce graft-versus-leukemia (GvL) reactions in patients with chronic myeloid leukemia (CIVIL) relapsing after allogeneic bone marrow transplantation (BMT), but the mechanisms of the antileukemic effect of DLI are unknown, and the procedure is complicated by graft-versus-host disease (GvHD) and graft failure. Here, we adapted a murine retroviral BMT model of Philadelphia(+) leukemia by combining allogeneic bone marrow (BM) from C57Bl/6 (H-2(b)) mice with BCR-ABL-transduced Balb/c (H-2(d)) BM, inducing mixed chimerism and myeloproliferative disease in recipients resembling relapse of CML following allogeneic BMT. Infusions of allogeneic splenocytes eliminated BCR-ABL-induced CML-like disease in the majority of mixed chimeras, with significant GvL effects mediated by both CD4(+) and CD4(-) cells. BCR-ABL-induced acute B-lymphoblastic leukemia was also eradicated by DLI in major histocompatibility complex (MHC)-mismatched chimeras. Most DLI-treated mice converted to full allogeneic chimerism but succumbed frequently to GvHD or graft failure. When MHC-matched B10.D2 (H-2(d)) mice were the allogeneic donors, CML-like disease was more resistant to DILL These results suggest that depletion of CD8(+) cells from DLI could impair GvL against CML, while increased MHC disparity between donor and recipient may improve the responsiveness of Philadelphia(+) B-lymphoblastic leukemia to DLI. (C) 2004 by The American Society of Hematology. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. Harvard Univ, Sch Med, Inst Biomed Res, Ctr Blood Res, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, 750 Washington St,Box 5609, Boston, MA 02111 USA. EM rvanetten@tufts-nemc.org FU NHLBI NIH HHS [HL56949] NR 34 TC 4 Z9 7 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2004 VL 104 IS 13 BP 4236 EP 4244 DI 10.1182/blood-2004-06-2229 PG 9 WC Hematology SC Hematology GA 877VC UT WOS:000225601000062 PM 15308567 ER PT J AU Liu, G Zhou, W Park, S Wang, LI Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC AF Liu, G Zhou, W Park, S Wang, LI Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC TI The SOD2 Val/Val genotype enhances the risk of nonsmall cell lung carcinoma by p53 and XRCC1 polymorphisms SO CANCER LA English DT Article DE SOD2; XRCC1; p53; genetic polymorphisms; lung carcinoma; case-control study ID MANGANESE SUPEROXIDE-DISMUTASE; REPAIR GENE XRCC1; DNA-REPAIR; CANCER RISK; MALIGNANT PHENOTYPE; AFRICAN-AMERICANS; BLADDER-CANCER; EXPRESSION; SMOKING; ASSOCIATION AB BACKGROUND. Exogenous reactive oxygen species (ROS) induces DNA damage. Manganese superoxide dismutase (SOD2) catalyzes the dismutation of superoxide radicals, a major type of ROS, into hydrogen peroxide. p53 is a tumor suppressor gene, and X-ray cross-complementing group 1 (XRCC1) is involved in the base-excision repair of ROS-induced DNA damage. METHODS. The authors investigated whether the SOD2 Ala16Val polymorphism modifies the associations between p53 Arg72Pro and XRCC1 Arg399Gln polymorphisms and the risk of nonsmall cell lung carcinoma (NSCLC) in a case-control study of 935 Caucasian patients with NSCLC and 1233 healthy control participants. The results were analyzed using logistic regression models that were adjusted for possible confounding variables. RESULTS. There was no association between p53 or XRCC1 polymorphism and NSCLC risk for individuals with SOD2 Ala/Ala or Ala/Val genotype. For individuals with the SOD2 Val/Val genotype, greater risks were found in association with p53 (variant Pro allele vs. Arg/Arg), XRCC1 (variant Gln allele vs. Arg/Arg), and the combination of the two polymorphisms ("double variant" vs. "double wild type"), with the adjusted odds ratios (ORs) of 1.84 (95% confidence interval [95% Cl], 1.20-2.82), 1.39 (95% CI, 0.98-2.21), and 2.54 (95% CI, 1.38-4.68), respectively. Furthermore, the greater risk for the double variant of p53 and XRCC1 in the SOD2 Val/Val genotype group was specific only for patients with adenocarcinoma and not for patients with squamous cell carcinoma, with adjusted ORs of 3.31 (95% Cl, 1.68-6.51) and 0.69 (95% CI, 0.24-2.02), respectively. CONCLUSIONS. The SOD2 Val/Val genotype may increase the risk of NSCLC carried by XRCC1 and p53 polymorphisms, particularly for adenocarcinoma. (C) 2004 American Cancer Society. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Christiani, DC (reprint author), 665 Huntington Ave,Bldg 1-1402, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES/CA06409, ES00002]; PHS HHS [T3206709] NR 43 TC 34 Z9 35 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2004 VL 101 IS 12 BP 2802 EP 2808 DI 10.1002/cncr.20716 PG 7 WC Oncology SC Oncology GA 878HK UT WOS:000225637200011 PM 15534883 ER PT J AU Polci, R Peng, AM Chen, PL Riley, DJ Chen, YM AF Polci, R Peng, AM Chen, PL Riley, DJ Chen, YM TI NIMA-related protein kinase 1 is involved early in the ionizing radiation-induced DNA damage response SO CANCER RESEARCH LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; EARLY PARTICIPANT; PROTEIN-KINASES; GENE; SEQUENCE; REGION; BRCA1; NEK1 AB Cellular functions of the NimA-related mammalian kinase Nek1 have not been demonstrated to date. Here we show that Nek1 is involved early in the DNA damage response induced by ionizing radiation (IR) and that Nek1 is important for cells to repair and recover from DNA damage. When primary or transformed cells are exposed to IR, Nek1 kinase activity is increased within 4 minutes, and Nek1 expression is up-regulated shortly thereafter and sustained for hours. At the same early time frame after IR that its kinase activity is highest, a portion of Nek1 redistributes in cells from cytoplasm to discrete nuclear foci at sites of DNA double-strand breaks. There it colocalizes with gamma-H2AX and NFBD1/MDC1, two key proteins involved very early in the response to IR-induced DNA double-strand breaks. Finally, Nek1-deficient fibroblasts are much more sensitive to the effects of IR-induced DNA damage than otherwise identical fibroblasts expressing Nek1. These results suggest that Nek1 may function as a kinase early in the DNA damage response pathway. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78229 USA. Univ Roma La Sapienza, Dept Clin Sci, Div Nephrol, Policlin Umberto I, Rome, Italy. S Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. RP Chen, YM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cheny@uthscsa.edu FU NCI NIH HHS [R01-CA85605]; NIDDK NIH HHS [1P50-DK061597, R01-DK61626] NR 17 TC 29 Z9 29 U1 2 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 DEC 15 PY 2004 VL 64 IS 24 BP 8800 EP 8803 DI 10.1158/0008-5472.CAN-04-2243 PG 4 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200002 PM 15604234 ER PT J AU Bentires-Alj, M Paez, JG David, FS Keilhack, H Halmos, B Naoki, K Maris, JM Richardson, A Bardelli, A Sugarbaker, DJ Richards, WG Du, JY Girard, L Minna, JD Loh, ML Fisher, DE Velculescu, VE Vogelstein, B Meyerson, M Sellers, WR Neel, BG AF Bentires-Alj, M Paez, JG David, FS Keilhack, H Halmos, B Naoki, K Maris, JM Richardson, A Bardelli, A Sugarbaker, DJ Richards, WG Du, JY Girard, L Minna, JD Loh, ML Fisher, DE Velculescu, VE Vogelstein, B Meyerson, M Sellers, WR Neel, BG TI Activating mutations of the Noonan syndrome-associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia SO CANCER RESEARCH LA English DT Article ID TYROSINE-PHOSPHATASE SHP-2; LUNG-CANCER; BRAF GENE; PTPN11; LEUKEMOGENESIS; ADENOCARCINOMA; MECHANISMS; GEFITINIB AB The SH2 domain-containing protein-tyrosine phosphatase PTPN11 (Shp2) is required for normal development and is an essential component of signaling pathways initiated by growth factors, cytokines, and extracellular matrix. In many of these pathways, Shp2 acts upstream of Ras. About 50% of patients with Noonan syndrome have germ-line PTPN11 gain of function mutations. Associations between Noonan syndrome and an increased risk of some malignancies, notably leukemia and neuroblastoma, have been reported, and recent data indicate that somatic PTPN11 mutations occur in children with sporadic juvenile myelomonocytic leukemia, myelodysplasic syndrome, B-cell acute lymphoblastic leukemia, and acute myelogenous leukemia (AML). Juvenile myelomonocytic leukemia patients without PTPN11 mutations have either homozygotic NF-1 deletion or activating RAS mutations. Given the role of Shp2 in Ras activation and the frequent mutation of RAS in human tumors, these data raise the possibility that PTPN11 mutations play a broader role in cancer. We asked whether PTPN11 mutations occur in other malignancies in which activating RAS mutations occur at low but significant frequency. Sequencing of PTPN11 from 13 different human neoplasms including breast, lung, gastric, and neuroblastoma tumors and adult AML and acute lymphoblastic leukemia revealed 11 missense mutations. Five are known mutations predicted to result in an activated form of Shp2, whereas six are new mutations. Biochemical analysis confirmed that several of the new mutations result in increased Shp2 activity. Our data demonstrate that mutations in PTPN11 occur at low frequency in several human cancers, especially neuroblastoma and AML, and suggest that Shp2 may be a novel target for antineoplastic therapy. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Biol Program, Boston, MA 02215 USA. Univ Liege, Ctr Cellular & Mol Therapy, Lab Med Chem & Human Genet, Liege, Belgium. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Turin, Sch Med, Inst Canc Res & Treatment, Oncogenom Ctr, Turin, Italy. Dana Farber Canc Inst, Dept Surg Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Johns Hopkins Univ, Howard Hughes Med Inst, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Harvard Univ, Sch Med, Dept Med, Broad Inst, Boston, MA USA. MIT, Boston, MA USA. RP Bentires-Alj, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Canc Biol Program, New Res Bldg 1038,77 Louis Pasteur Ave, Boston, MA 02215 USA. EM mbentire@bidmc.harvard.edu RI Meyerson, Matthew/E-7123-2012; Mohamed, Bentires-Alj/F-4484-2015 OI Mohamed, Bentires-Alj/0000-0001-6344-1127 FU NCI NIH HHS [CA43460, R01 CA49152] NR 20 TC 252 Z9 266 U1 3 U2 17 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 DEC 15 PY 2004 VL 64 IS 24 BP 8816 EP 8820 DI 10.1158/0008-5472.CAN-04-1923 PG 5 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200006 PM 15604238 ER PT J AU Berger, R Febbo, PG Majumder, PK Zhao, JJ Mukherjee, S Signoretti, S Campbell, KT Sellers, WR Roberts, TM Loda, M Golub, TR Hahn, WC AF Berger, R Febbo, PG Majumder, PK Zhao, JJ Mukherjee, S Signoretti, S Campbell, KT Sellers, WR Roberts, TM Loda, M Golub, TR Hahn, WC TI Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells SO CANCER RESEARCH LA English DT Article ID RAS ONCOGENE MUTATIONS; INTRAEPITHELIAL NEOPLASIA; GENE-EXPRESSION; T-ANTIGEN; MALIGNANT TRANSFORMATION; CANCER SPECIMENS; MOUSE MODELS; IN-VITRO; CARCINOMA; RECEPTOR AB Androgen ablation is the primary treatment modality for patients with metastatic prostate cancer; however, the role of androgen receptor signaling in prostate cancer development remains enigmatic. Using a series of genetically defined immortalized and tumorigenic human prostate epithelial cells, we found that introduction of the androgen receptor induced differentiation of transformed prostate epithelial cells to a luminal phenotype reminiscent of organ-confined prostate cancer when placed in the prostate microenvironment. Moreover, androgen receptor expression converted previously androgen-independent, tumorigenic prostate epithelial cells into cells dependent on testosterone for tumor formation. These observations indicate that androgen receptor expression is oncogenic and addictive for the human prostate epithelium. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Febbo, PG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. EM phil.febbo@duke.edu; William_Hahn@dfci.harvard.edu OI Mukherjee, Sayan/0000-0002-6715-3920 FU NCI NIH HHS [P01 CA50661, K23 CA089031, K01 CA94223] NR 62 TC 122 Z9 123 U1 1 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 DEC 15 PY 2004 VL 64 IS 24 BP 8867 EP 8875 DI 10.1158/0008-5472.CAN-04-2938 PG 9 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200014 PM 15604246 ER PT J AU Shah, RB Mehra, R Chinnaiyan, AM Shen, RL Ghosh, D Zhou, M MacVicar, GR Varambally, S Harwood, J Bismar, TA Kim, R Rubin, MA Pienta, KJ AF Shah, RB Mehra, R Chinnaiyan, AM Shen, RL Ghosh, D Zhou, M MacVicar, GR Varambally, S Harwood, J Bismar, TA Kim, R Rubin, MA Pienta, KJ TI Androgen-independent prostate cancer is a heterogeneous group of diseases: Lessons from a rapid autopsy program SO CANCER RESEARCH LA English DT Article ID CELLULAR IMAGING-SYSTEM; TRANSCRIPTION FACTOR-I; NEUROENDOCRINE EXPRESSION; TISSUE MICROARRAYS; GENE-EXPRESSION; COA RACEMASE; PROGRESSION; CARCINOMA; PROTEIN; BIOMARKER AB Understanding the biology of prostate cancer metastasis has been limited by the lack of tissue for study. We studied the clinical data, distribution of prostate cancer involvement, morphology, immunophenotypes, and gene expression from 30 rapid autopsies of men who died of hormone-refractory prostate cancer. A tissue microarray was constructed and quantitatively evaluated for expression of prostate-specific antigen, androgen receptor, chromogranin, synaptophysin, MIB-1, and alpha-methyl-acylCoA-racemase markers. Hierarchical clustering of 16 rapid autopsy tumor samples was performed to evaluate the cDNA expression pattern associated with the morphology. Comparisons were made between patients as well as within the same patient. Metastatic hormone-refractory prostate cancer has a heterogeneous morphology, immunophenotype, and genotype, demonstrating that "metastatic disease" is a group of diseases even within the same patient. An appreciation of this heterogeneity is critical to evaluating diagnostic and prognostic biomarkers as well as to designing therapeutic targets for advanced disease. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Med Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Shah, RB (reprint author), Univ Michigan, Sch Med, Dept Pathol, 2G332 UH,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM rajshah@umich.edu RI Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50CA69568, CA 97063, CA102872]; NIA NIH HHS [R01AG21404] NR 45 TC 377 Z9 386 U1 2 U2 13 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 DEC 15 PY 2004 VL 64 IS 24 BP 9209 EP 9216 DI 10.1158/0008-5472.CAN-04-2442 PG 8 WC Oncology SC Oncology GA 880SJ UT WOS:000225809200062 PM 15604294 ER PT J AU Astrakas, LG Zurakowski, D Tzika, AA Zarifi, MK Anthony, DC De Girolami, U Tarbell, NJ Black, PM AF Astrakas, LG Zurakowski, D Tzika, AA Zarifi, MK Anthony, DC De Girolami, U Tarbell, NJ Black, PM TI Noninvasive magnetic resonance spectroscopic imaging biomarkers to predict the clinical grade of pediatric brain tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTON MR SPECTROSCOPY; OPERATING CHARACTERISTIC CURVES; P-31 NMR-SPECTROSCOPY; APOPTOTIC CELL-DEATH; IN-VIVO; RAT GLIOMA; GENE-THERAPY; AUTOMATED CLASSIFICATION; PHOSPHOLIPID-METABOLISM; NEURAL-NETWORKS AB The diagnosis and therapy of childhood brain tumors, most of which are low grade, can be complicated because of their frequent adjacent location to crucial structures, which limits diagnostic biopsy. Also, although new prognostic biomarkers identified by molecular analysis or DNA microarray gene profiling are promising, they too depend on invasive biopsy. Here, we test the hypothesis that combining information from biologically important intracellular molecules (biomarkers), noninvasively obtained by proton magnetic resonance spectroscopic imaging, will increase the diagnostic accuracy in determining the clinical grade of pediatric brain tumors. We evaluate the proton magnetic resonance spectroscopic imaging exams for 66 children with brain tumors. The intracellular biomarkers for choline-containing compounds (Cho), N-acetylaspartate, total creatine, and lipids and/or lactate were measured at the highest Cho region and normalized to the surrounding healthy tissue total creatine. Neuropathological grading was done with WHO criteria. Normalized Cho and lipids and/or lactate were elevated in high-grade (n = 23) versus low-grade (n = 43) tumors, which multiple logistic regression confirmed are independent predictors of tumor grade (for Cho, odds ratio 24.8, P < 0.001; and for lipids and/or lactate, odds ratio 4.4, P < 0.001). A linear combination of normalized Cho and lipids and/or lactate that maximizes diagnostic accuracy was calculated by maximizing the area under the receiver operating characteristic curve. Proton magnetic resonance spectroscopic imaging, although not a proxy for histology, provides noninvasive, in vivo biomarkers for predicting clinical grades of pediatric brain tumors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab,Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Univ Missouri, Dept Pathol & Anat Sci, Columbia, MO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Tzika, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,NMR Surg Lab,Shriners Burns Inst, 51 Blossom St,Room 261, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011; OI Anthony, Douglas/0000-0002-3815-2240 NR 72 TC 72 Z9 72 U1 2 U2 5 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 DEC 15 PY 2004 VL 10 IS 24 BP 8220 EP 8228 DI 10.1158/1078-0432.CCR-04-0603 PG 9 WC Oncology SC Oncology GA 882SE UT WOS:000225957800014 PM 15623597 ER PT J AU Freytes, CO Ratanatharathorn, V Taylor, C Abboud, C Chesser, N Restrepo, A Arango, J Odenheimer, D AF Freytes, CO Ratanatharathorn, V Taylor, C Abboud, C Chesser, N Restrepo, A Arango, J Odenheimer, D TI Phase I/II randomized trial evaluating the safety and clinical effects of repifermin administered to reduce mucositis in patients undergoing autologous hematopoietic stem cell transplantation SO CLINICAL CANCER RESEARCH LA English DT Article ID KERATINOCYTE GROWTH FACTOR-2; BONE-MARROW-TRANSPLANTATION; COMPLICATIONS; CHEMOTHERAPY; EFFICACY; KGF-2 AB Purpose: To evaluate the safety of repifermin (keratinocyte growth factor-2) administered before and after autologous hematopoietic stem cell transplantation (auto-HSCT). A preliminary analysis of the ability of keratinocyte growth factor-2 to prevent mucositis was also done. Experimental Design: Forty-two patients received intravenous repifermin (25 mug/kg or 50 mug/kg) or placebo for 3 days before their auto-HSCT conditioning regimen and for up to 10 days after auto-HSCT. Within each dose level, 14 patients were randomized to repifermin and 7 patients to placebo. Clinical evaluations of mucositis were scheduled before auto-HSCT conditioning regimen, on the day of transplant, and three times per week until mucositis resolved. Results: In general, the incidence of adverse events was similar for patients treated with repifermin and placebo. No clinically meaningful differences were noted among treatment groups for clinical laboratory variables. Treatment groups experienced similar time to engraftment. The frequency of Grade 2 to 4 mucositis was 100% for patients in the placebo group, 64% for patients in the 25 mug/kg group (P = 0.041 versus placebo), and 50% for patients in the 50 mug/kg group (P = 0.006 versus placebo). Results of other endpoints, including pain on swallowing and use of pain medication specifically for mucositis, suggested a better outcome for patients in the 50 mug/kg group compared with the placebo and 25 mug/kg groups. Conclusions: Repifermin was well tolerated. Repifermin given before and after auto-HSCT seems to be active in reducing mucositis, but a larger trial will be necessary to determine the efficacy of repifermin with this dose schedule. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Tex Vet Hlth Care Syst, San Antonio, TX USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Arizona Canc Ctr, Tucson, AZ USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Human Genome Sci, Rockville, MD USA. RP Freytes, CO (reprint author), Univ Texas, Hlth Sci Ctr, Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freytes@uthscsa.edu NR 18 TC 39 Z9 42 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 DEC 15 PY 2004 VL 10 IS 24 BP 8318 EP 8324 DI 10.1158/1078-0432.CCR-04-1118 PG 7 WC Oncology SC Oncology GA 882SE UT WOS:000225957800025 PM 15623608 ER PT J AU Connick, E Kane, MA White, IE Ryder, J Campbell, TB AF Connick, E Kane, MA White, IE Ryder, J Campbell, TB TI Immune reconstitution inflammatory syndrome associated with Kaposi sarcoma during potent antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HERPESVIRUS; AIDS; INFECTION; GROWTH; CELLS AB Rapidly progressive Kaposi sarcoma (KS) lesions with lymphadenopathy and tissue swelling occurred in a patient during antiretroviral treatment, despite an increased CD4(+) lymphocyte count and decreased HIV-1 level and KS-associated herpesvirus replication, suggesting immune reconstitution inflammatory syndrome. Inflammation resolved coincident with decreases in the CD4(+) lymphocyte count during paclitaxel treatment, whereas KS cleared only after prolonged antiretroviral therapy and chemotherapy. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Med Oncol Sect, Denver, CO USA. RP Connick, E (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Box B168,4200 E 9th Ave, Denver, CO 80262 USA. EM liz.connick@uchsc.edu FU NCI NIH HHS [CA79389]; NIAID NIH HHS [U01 AI 32770, AI054907] NR 12 TC 50 Z9 55 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 DEC 15 PY 2004 VL 39 IS 12 BP 1852 EP 1855 DI 10.1086/426078 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JJ UT WOS:000227492200019 PM 15578411 ER PT J AU Eron, JJ Bartlett, JA Santana, JL Bellos, NC Johnson, J Keller, A Kuritzkes, DR St Clair, MH Johnson, VA AF Eron, JJ Bartlett, JA Santana, JL Bellos, NC Johnson, J Keller, A Kuritzkes, DR St Clair, MH Johnson, VA TI Persistent antiretroviral activity of nucleoside analogues after prolonged zidovudine and lamivudine therapy as demonstrated by rapid loss of activity after discontinuation SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; lamivudine; zidovudine; resistance; discontinuation ID VIROLOGICAL FAILURE; VIREMIA; RESISTANCE; INFECTION; COHORT AB Antiretroviral (ARV) treatment decisions are difficult for HIV-1-infected patients on complex treatment regimens who have partial suppression of HIV-1 replication and limited treatment options. Information on the ARV activity of the components of a complex regimen would be useful. Sixteen subjects who had received prolonged therapy with zidovudine (ZDV) and lamivudine (3TC), with a median duration of 32.5 months, were discontinuing this dual-nucleoside regimen and volunteered to have plasma HIV-1 RNA levels monitored over the 2 weeks after discontinuation. All subjects experienced an increase in HIV-1 RNA after discontinuation, with a median increase of 0.54 log(10) copies/mL over 2 weeks (range: 0.31-1.71; P < 0.001). An inverse correlation existed between the decline in HIV-1 RNA levels over 2 to 3 years on nucleoside analogue therapy and the increase over the 10 to 14 days off therapy (Spearman r = -0.53; P = 0.036). Over the 2-week period, a subset of individuals who had genotype testing at multiple reverse transcriptase codons associated with ZDV and 3TC resistance had no changes in genotype off therapy. Nucleoside analogue reverse transcriptase inhibitors may have continued ARV activity despite long durations of partially suppressive therapy and the presence of resistant HIV-1. C1 Univ N Carolina, AIDS Clin Res Unit, Chapel Hill, NC USA. Duke Univ, Ctr AIDS Res, Durham, NC USA. Univ Puerto Rico, San Juan AIDS Project, San Juan, PR 00936 USA. SW Infect Dis Associates Dallas, Dallas, TX USA. GlaxoSmithKline, Infect Dis Med Dev Ctr, Res Triangle Pk, NC USA. Brigham & Womens Hosp, Sect Retroviral Therapeut, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Alabama, Sch Med, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Div Infect Dis, Birmingham, AL USA. RP Eron, JJ (reprint author), Univ N Carolina, AIDS Clin Res Unit, 211A W Cameron Ave, Chapel Hill, NC USA. EM jeron@med.unc.edu FU NCRR NIH HHS [RR00046]; NIAID NIH HHS [AI50410, AI40876] NR 13 TC 30 Z9 30 U1 0 U2 0 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 DEC 15 PY 2004 VL 37 IS 5 BP 1581 EP 1583 DI 10.1097/00126334-200412150-00009 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 881FY UT WOS:000225850000009 PM 15577413 ER PT J AU Chi, SN Gardner, SL Levy, AS Knapp, EA Miller, DC Wisoff, JH Weiner, HL Finlay, JL AF Chi, SN Gardner, SL Levy, AS Knapp, EA Miller, DC Wisoff, JH Weiner, HL Finlay, JL TI Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 11th International Symposium on Pediatric Neuro-Oncology CY JUN, 2004 CL Boston, MA ID MALIGNANT BRAIN-TUMORS; BONE-MARROW RESCUE; ACUTE LYMPHOBLASTIC-LEUKEMIA; POSTOPERATIVE CHEMOTHERAPY; MYELOABLATIVE CHEMOTHERAPY; CANCER GROUP; SURVIVAL; AGE; TRANSPLANTATION; NEUROBLASTOMA AB Purpose To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. Patients and Methods From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk X three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d X 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. Results Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81 %), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. Conclusion This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies. C1 NYU, Med Ctr, Div Pediat Oncol, New York, NY 10016 USA. NYU, Med Ctr, Div Neuroradiol, New York, NY 10016 USA. NYU, Med Ctr, Div Neuropathol, New York, NY 10016 USA. NYU, Med Ctr, Div Pediat Neurosurg, New York, NY 10016 USA. RP Chi, SN (reprint author), Dana Farber Canc Inst, 44 Binney St,SW331, Boston, MA 02115 USA. EM susan_chi@dfci.harvard.edu OI Wisoff, Jeffrey/0000-0003-3303-2220; gardner, sharon/0000-0002-8857-5487 NR 28 TC 95 Z9 100 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 DEC 15 PY 2004 VL 22 IS 24 BP 4881 EP 4887 DI 10.1200/JCO.2004.12.126 PG 7 WC Oncology SC Oncology GA 886OT UT WOS:000226238900005 PM 15611503 ER PT J AU Bober, SL Hoke, LA Duda, RB Regan, MM Tung, NM AF Bober, SL Hoke, LA Duda, RB Regan, MM Tung, NM TI Decision-making about tamoxifen in women at high risk for breast cancer: Clinical and psychological factors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL ADJUVANT BREAST; OVARIAN-CANCER; CHEMOPREVENTION; HEALTH; ADHERENCE; WORRY; CARE; PERCEPTION; PREVENTION; AVOIDANCE AB Purpose To explore the health-related and psychological factors that influence decision making about tamoxifen (Nolvadex; AstraZeneca, Waltham, MA) chemoprevention in women at increased risk for developing breast cancer. Methods This study involves the assessment of 129 women eligible to take tamoxifen following cancer-risk counseling. Treatment decision and decision satisfaction were measured at 2 and 4 months following counseling. Health-related factors included physician recommendation, personal and family-related health history, and concern about side effects. Psychological factors included breast cancer-related anxiety, risk perception, and depression. Results At 2 months' follow-up, 44% of participants declined tamoxifen treatment. This number increased to 49% at 4 months. Personal and family health history were not related to the decision, but history of abnormal biopsy did predict tamoxifen use. Physician recommendation was highly correlated with treatment decision. Concern about side effects was related to the decision to decline treatment. Breast cancer-related anxiety and heightened risk perception were associated with the decision to take tamoxifen. However, anxiety and psychological distress were also negatively related to treatment satisfaction. Conclusion Decision-making about tamoxifen is complex, and many eligible women decline treatment or remain undecided. Findings call for further educational follow-up with high-risk women after they undergo initial counseling. Factors related to misperceptions of risk and side effects, as well as psychological distress, may be particularly important targets for intervention. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bober, SL (reprint author), Dana Farber Canc Inst, David B Perini Qual Life Clin, D321,44 Binney St, Boston, MA 02115 USA. EM sharon_bober@dfci.harvard.edu NR 32 TC 70 Z9 71 U1 0 U2 3 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 DEC 15 PY 2004 VL 22 IS 24 BP 4951 EP 4957 DI 10.1200/JCO.2004.05.192 PG 7 WC Oncology SC Oncology GA 886OT UT WOS:000226238900014 PM 15598980 ER PT J AU Kim, WY Kaelin, WG AF Kim, WY Kaelin, WG TI Role of VHL gene mutation in human cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID VON-HIPPEL-LINDAU; TUMOR-SUPPRESSOR GENE; RENAL-CELL-CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; CENTRAL-NERVOUS-SYSTEM; SPORADIC CEREBELLAR HEMANGIOBLASTOMAS; UBIQUITIN-PROTEASOME PATHWAY; BIOLOGICALLY-ACTIVE PRODUCT; RECEPTOR TYROSINE KINASES AB Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene causes the von Hippel-Lindau hereditary cancer syndrome, and somatic mutations of this gene have been linked to the development of sporadic hemangioblastomas and clear-cell renal carcinomas. The VHL tumor suppressor protein (pVHL), through its oxygen-dependent polyubiquitylation of hypoxia-inducible factor (HIF), plays a central role in the mammalian oxygen-sensing pathway. This interaction between pVHL and HIF is governed by post-translational prolyl hydroxylation of HIF in the presence of oxygen by a conserved family of Egl-nine (EGLN) enzymes. In the absence of pVHL, HIF becomes stabilized and is free to induce the expression of its target genes, many of which are important in regulating angiogenesis, cell growth, or cell survival. Moreover, preliminary data indicate that HIF plays a critical role in pVHL-defective tumor formation, raising the possibility that drugs directed against HIF or its downstream targets (such as vascular endothelial growth factor) might one day play a role in the treatment of hemangioblastoma and renal cell carcinoma. On the other hand, clear genotype-phenotype correlations are emerging in VHL disease and can be rationalized if pVHL has functions separate from its control of HIF. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 176 TC 543 Z9 558 U1 6 U2 25 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 DEC 15 PY 2004 VL 22 IS 24 BP 4991 EP 5004 DI 10.1200/JCO.2004.05.061 PG 14 WC Oncology SC Oncology GA 886OT UT WOS:000226238900019 PM 15611513 ER PT J AU Ayanian, JZ Chrischilles, EA Fletcher, RH Fouad, MN Harrington, DP Kahn, KL Kiefe, CI Lipscomb, J Malin, JL Potosky, AL Provenzale, DT Sandler, RS van Ryn, M Wallace, RB Weeks, JC West, DW AF Ayanian, JZ Chrischilles, EA Fletcher, RH Fouad, MN Harrington, DP Kahn, KL Kiefe, CI Lipscomb, J Malin, JL Potosky, AL Provenzale, DT Sandler, RS van Ryn, M Wallace, RB Weeks, JC West, DW TI Understanding cancer treatment and outcomes: The Cancer Care Outcomes Research and Surveillance Consortium (vol 22, pg 2992, 2004) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Correction C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Gen Med,Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med Hlth Serv Res, Los Angeles, CA USA. NCI, Div Canc Control & Populat Sci, Rockville, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Durham, NC USA. Univ N Carolina, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC USA. Dept Vet Affairs Med Ctr, Minneapolis, MN USA. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. No Calif Canc Ctr, Union City, CA USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Gen Med,Dept Hlth Care Policy, Boston, MA 02115 USA. RI VAN RYN, MICHELLE/B-1664-2010 NR 1 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC 15 PY 2004 VL 22 IS 24 BP 5026 EP 5026 DI 10.1200/JCO.2004.10.909 PG 1 WC Oncology SC Oncology GA 886OT UT WOS:000226238900032 ER PT J AU Tian, CR Bagley, J Forman, D Iacomini, J AF Tian, CR Bagley, J Forman, D Iacomini, J TI Induction of central tolerance by mature T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSPLANTATION TOLERANCE; GENE-THERAPY; ADULT THYMUS; ANTIGENS; PERSIST; REENTRY; MIGRATE; MARROW; MICE AB Induction of immunological tolerance is highly desirable for the treatment and prevention of autoimmunity, allergy, and organ transplant rejection. Adoptive transfer of MHC class I disparate mature T cells at the time of reconstitution of mice with syngeneic bone marrow resulted in specific tolerance to allogeneic skin grafts that were matched to the T cell donor strain. Mature allogeneic T cells survived long-term in reconstituted hosts and were able to re-enter the thymus. Analysis of T cell development using transgenic mice expressing an alloantigen-reactive TCR revealed that expression of allogeneic MHC class I on adoptively transferred mature T cells mediated negative selection of developing alloreactive T cells in the thymus. Thus, mature allogeneic T cells are able to mediate central deletion of alloreactive cells and induce transplantation tolerance without the requirement for any other alloantigen-expressing cell type. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149,13th St, Boston, MA 02129 USA. EM iacomini@helix.mgh.harvard.edu FU NIAID NIH HHS [R01 AI43619, T32 AI07529] NR 23 TC 28 Z9 28 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7217 EP 7222 PG 6 WC Immunology SC Immunology GA 878RT UT WOS:000225665100015 PM 15585843 ER PT J AU Re, F Strominger, JL AF Re, F Strominger, JL TI IL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-2; SIGNALING PATHWAY; CUTTING EDGE; IN-VITRO; T-CELLS; INTERFERON-GAMMA; GENE-EXPRESSION; MACROPHAGES; RESPONSES; MICE AB Recognition of microbial products through TLRs triggers the expression of several cytokines that regulate innate and adaptive immunity. Signaling by various TLRs is not equivalent and leads to differential gene induction. This study analyzed the responses of human dendritic cells (DCs) and PBMCs stimulated with agonists of TLR2, TLR3, TLR4, TLR5, and TLR7, first individually and then in combination. Several cytokines were equally induced by all TLR agonists, but four genes, IFN-beta, IFN-gamma-inducible protein 10 (IP-10), IL-12p35, and IL-15, showed a very restricted pattern of induction. Thus, each TLR appears to possess a distinctive ability to activate DCs or PBMCs, suggesting that TLR-mediated responses cannot be simply cataloged as resembling either TLR2 (MyD88 dependent) or TLR4 (MyD88 independent) and that other signaling modalities may exist. The analysis of DC and PBMC activation by combinations of TLR agonists revealed that TLR2 agonists are able to block the induction of IP-10, IL-12p35, and IFN-gamma, but not IL-15 and IFN-beta, by TLR3 and TLR4. TLR2 stimulation led to rapid release of IL-10 that is responsible for inhibition of IP-10 and IL-12p35 induction. Cross-talk between different TLRs may modify the primary responses of TLR to their agonist, adding a further level of complexity to the regulation of innate immunity. C1 Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept AIDS, Boston, MA 02115 USA. RP Re, F (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. EM fre@utmem.edu FU NIAID NIH HHS [AI-54665, AI-49524] NR 43 TC 161 Z9 169 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2004 VL 173 IS 12 BP 7548 EP 7555 PG 8 WC Immunology SC Immunology GA 878RT UT WOS:000225665100054 PM 15585882 ER PT J AU Amirnovin, R Williams, ZM Cosgrove, GR Eskandar, EN AF Amirnovin, R Williams, ZM Cosgrove, GR Eskandar, EN TI Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Parkinson's disease; subthalamic nucleus; oscillations; neurons; visual guidance; movement ID BASAL GANGLIA; PALLIDAL NEURONS; GLOBUS-PALLIDUS; MOTOR CORTEX; 2 PARTS; NUCLEUS; SYNCHRONIZATION; STIMULATION; PALLIDOTOMY; DISORDERS AB There is considerable evidence that abnormal oscillatory activity in the basal ganglia contributes to the pathogenesis of Parkinson's disease. However, little is known regarding the relationship of oscillations to volitional movements. Our goal was to evaluate the dynamics of oscillatory activity at rest and during movement. We performed microelectrode recordings from the subthalamic nucleus (STN) of patients undergoing deep brain stimulation surgery. During recordings, the patients used a joystick to guide a cursor to one of four targets on a monitor. We recorded 184 cells and 47 pairs of cells in 11 patients. At rest, 26 cells (14%) demonstrated significant oscillatory activity, with a mean frequency of 18 Hz. During movement, this oscillatory activity was either reduced or completely abolished in all of the cells. At rest, 18 pairs (38%) of cells in five patients exhibited synchronized oscillatory activity, with a mean frequency of 15 Hz. In 17 of the 18 pairs, both of the cells exhibited oscillations, and, in one pair, only one of the cells was oscillatory. These synchronized oscillations were also significantly decreased with movement. There was a strong inverse correlation between firing rates and oscillatory activity. As the firing rates increased with movement, there was a decrease in oscillatory activity. These findings suggest that visually guided movements are associated with a dampening and desynchronization of oscillatory activity in STN neurons. One possible explanation for these observations is that the increased cortical drive associated with movement preparation and execution leads to a transient dampening of STN oscillations, hence facilitating movement. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg,Ambulatory Care Ctr 021, Boston, MA 02114 USA. RP Eskandar, EN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg,Ambulatory Care Ctr 021, 15 Parkman St, Boston, MA 02114 USA. EM eeskandar@partners.org FU NINDS NIH HHS [NS41851] NR 29 TC 63 Z9 63 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2004 VL 24 IS 50 BP 11302 EP 11306 DI 10.1523/JNEUROSCI.3242-04.2004 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 880CK UT WOS:000225766200014 PM 15601936 ER PT J AU Sena-Esteves, M Tebbets, JC Steffens, S Crombleholme, T Flake, AW AF Sena-Esteves, M Tebbets, JC Steffens, S Crombleholme, T Flake, AW TI Optimized large-scale production of high titer lentivirus vector pseudotypes SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE lentivirus; vector; pseudotype; VSV-G; Mokola; Rabies; amphotropic; 10A1; LCMV ID EFFICIENT GENE-TRANSFER; RETROVIRAL VECTORS; IN-VIVO; ENVELOPE GLYCOPROTEINS; TRANSDUCTION PATTERNS; VIRUS GLYCOPROTEIN; NERVOUS-SYSTEM; MOUSE-BRAIN; EXPRESSION; CELLS AB The goal of the present study was to develop an efficient transient transfection method for large-scale production of high titer lentivirus vector stocks of eight different pseudotypes. The envelope genes used for this purpose were those from VSV-G, Mokola, Rabies, MLV-Ampho, MLV-10A1, LCMV-WE, and LCMV-Arm53b. All envelopes were cloned into phCMV, which yielded lentivirus vector titers one, two, or three orders of magnitude higher than the original plasmids for the Rabies, MLV-10A1, and MLV-Ampho envelopes, respectively. When these newly constructed envelope expression plasmids were used for packaging, treatment with sodium butyrate resulted in almost five-fold increase in titers for some of the pseudotypes, had no effect for others (VSV-G and Rabies), and negatively impacted titers for the LCMV-derived pseudotypes. Production of vectors in serum-free media yielded titers only slightly lower than those obtained in the presence of serum. The efficiency of concentrating vector supernatants by ultracentrifugation or ultrafiltration was compared, with higher recovery efficiencies for the latter method, but the highest titers for most pseudotypes were obtained by ultracentrifugation. The best conditions for each individual pseudotype yielded lentivirus vector stocks with titers above 1 x 10(9) tu/mL for most pseudotypes, and higher than 1 x 10(10) tu/mL for VSV-G. (C) 2004 Elsevier B.V. All rights reserved. C1 Childrens Hosp Philadelphia, Dept Surg, Abramson Res Ctr, Philadelphia, PA 19104 USA. RP Sena-Esteves, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM msesteves@partners.org NR 31 TC 165 Z9 177 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC 15 PY 2004 VL 122 IS 2 BP 131 EP 139 DI 10.1016/j.jviromet.2004.08.017 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 878FU UT WOS:000225632900001 PM 15542136 ER PT J AU Park, BH Pierce, MC de Boer, JF AF Park, BH Pierce, MC de Boer, JF TI Comment on "optical-fiber-based Mueller optical coherence tomography" SO OPTICS LETTERS LA English DT Article AB We comment on the recent Letter by Jiao et al. [Opt. Lett. 28, 1206 (2003)] in which a polarization-sensitive optical coherence tomography system was presented. Interrogating a sample with two orthogonal incident polarization states cannot always recover birefringence correctly. A previously presented fiber-based polarization -sensitive system was inaccurately characterized, and its method of eliminating the polarization distortion caused by single-mode optical fiber was presented earlier by Saxer et al. (C) 2004 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 7, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 7 TC 4 Z9 4 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD DEC 15 PY 2004 VL 29 IS 24 BP 2873 EP 2874 DI 10.1364/OL.29.002873 PG 2 WC Optics SC Optics GA 878YG UT WOS:000225682900013 PM 15645809 ER PT J AU Zisook, S Rush, AJ Albala, A Alpert, J Balasubramani, GK Fava, M Husain, M Sackeim, H Trivedi, M Wisniewski, S AF Zisook, S Rush, AJ Albala, A Alpert, J Balasubramani, GK Fava, M Husain, M Sackeim, H Trivedi, M Wisniewski, S TI Factors that differentiate early vs. later onset of major depression disorder SO PSYCHIATRY RESEARCH LA English DT Article DE major depressive disorder (M DD); STAR*D; age of onset; gender; antidepressants ID ILLNESS RATING-SCALE; PSYCHIATRIC-DISORDERS; SOCIAL-CONSEQUENCES; COMMUNITY SAMPLE; RISK-FACTORS; ADOLESCENT DEPRESSION; UNIPOLAR DEPRESSION; SYMPTOMATOLOGY IDS; GENDER-DIFFERENCES; MOOD DISORDERS AB This report explores the relationship between age of first onset of major depression and other demographic and clinical features in the first 1500 patients entering the Sequenced Treatment Alternative to Relieving Depression (STAR*D) study. Outpatients, 18-75 years of age, with nonpsychotic major depressive disorder (MDD) from either primary care or psychiatric practices constitute the population. Age of onset was defined at study intake by asking patients to estimate the age at which they experienced the onset of their first major depressive episode. This report divides the population in terms of pre-adult (before age 18) onset and adult (age 18 or later) onset. The results suggest that MDD that begins before age IS has a distinct set of demographic (female gender) and clinical correlates (longer duration of illness; longer current episodes: more. episodes; more suicidality; greater symptom severity; more psychiatric symptoms; associated with Axis I comorbidity: and more sadness, irritability, agitation and atypical symptom features), and it appears associated with significant psychosocial consequences (lower educational attainment and marriage rates). Thus, pre-adulthood onset MDD is a particularly severe and chronic condition. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif San Diego, Dept Psychiat, Sna Diego VA Med Ctr, La Jolla, CA 92093 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Univ Pittsburgh, Sch Publ Hlth, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. Columbia Univ, Dept Psychiat, New York State Psychiat Inst, New York, NY USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, Sna Diego VA Med Ctr, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM szisook@ucsd.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01 MH90003] NR 66 TC 67 Z9 71 U1 4 U2 13 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2004 VL 129 IS 2 BP 127 EP 140 DI 10.1016/j.psychres.2004.07.004 PG 14 WC Psychiatry SC Psychiatry GA 887PY UT WOS:000226319200002 PM 15590040 ER PT J AU Houck, PR Mazuradar, S Koru-Sengul, T Tang, G Mulsant, BH Pollock, BG Reynolds, CF AF Houck, PR Mazuradar, S Koru-Sengul, T Tang, G Mulsant, BH Pollock, BG Reynolds, CF TI Estimating treatment effects from longitudinal clinical trial data with missing values: comparative analyses using different methods SO PSYCHIATRY RESEARCH LA English DT Article DE intent-to-treat; missing data; mixed model; multiple imputation; maximum likelihood; depression ID MULTIPLE IMPUTATION; PATIENT DATA; MODELS; DEPRESSION; PSYCHIATRY; PROTOCOL AB The selection of a method for estimating treatment effects in an intent-to-treat analysis from clinical trial data with missing values often depends on the field of practice. The last observation carried forward (LOCF) analysis assumes that the responses do not change after dropout. Such an assumption is often unrealistic. Analysis with completers only requires that missing values occur completely at random (MCAR). Ignorable maximum likelihood (IML) and multiple imputation (MI) methods require that data are missing at random (MAR). We applied these four methods to a randomized clinical trial comparing anti-depressant effects in an elderly depressed group of patients using a mixed model to describe the course of the treatment effects. Results from an explanatory approach showed a significant difference between the treatments using LOCF and IML methods. Statistical tests indicate violation of the MCAR assumption favoring the flexible IML and MI methods. IML and MI methods were repeated under the pragmatic approach, using data collected after termination of protocol treatment and compared with previously reported results using piecewise splines and rescue (treatment adjustment) pragmatic analysis. No significant treatment differences were found. We conclude that attention to the missing-data mechanism should be an integral part in analysis of clinical trial data. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 UPMC, Hlth Syst, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA 15213 USA. RP Houck, PR (reprint author), UPMC, Hlth Syst, Western Psychiat Inst & Clin, Dept Psychiat, Thomas Detre Hall,3811 O Hara St, Pittsburgh, PA 15213 USA. EM houckpr@upmc.edu FU NIMH NIH HHS [MH30915, MH52247] NR 34 TC 41 Z9 41 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC 15 PY 2004 VL 129 IS 2 BP 209 EP 215 DI 10.1016/j.psychres.2004.08.001 PG 7 WC Psychiatry SC Psychiatry GA 887PY UT WOS:000226319200010 PM 15590048 ER PT J AU Quintana, J Wong, T Ortiz-Portillo, E Marder, SR Mazziotta, JC AF Quintana, J Wong, T Ortiz-Portillo, E Marder, SR Mazziotta, JC TI Anterior cingulate dysfunction during choice anticipation in schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE cognitive deficits; decision making; social functioning; foresight; fMRI; working memory ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; STROOP TASK-PERFORMANCE; SPATIAL WORKING-MEMORY; PREFRONTAL CORTEX; RESPONSE CONFLICT; NEURAL CIRCUITRY; PARIETAL CORTEX; FRONTAL-CORTEX AB The anterior cingulate cortex (ACGC) participates in selective attention. working memory (WM)), anticipation, and behavioral monitoring. Subjects with schizophrenia exhibit deficits in these mechanisms during selective attention and WM tasks. However, ACGC dysfunctions have not been specifically investigated during behavioral anticipation. whose deficits may relate to salient schizophrenic features such as foresight abnormalities and impaired social functioning and behavior. We thus studied ACGC function in relation to two aspects of WM, remembering information and anticipating responses. in control and schizophrenic subjects. We measured brain activation in eight subjects with schizophrenia and eight healthy volunteers using functional magnetic resonance imaging. All subjects performed stimulus-response delay tasks with color dots or facial expression diagrams as cues and either 50% or 100% response predictability. which emphasized demands on remembering the cues or anticipating the response for correct performance, respectively. We found a double dissociation of ACGC activtion between subject groups and task type. In controls, the ACGC became intensely activated during response anticipation (more extensively and bilaterally when the cues were colors than when they were facial diagrams) but remained at restin.. activity levels during remembering. In schizophrenic patients, significant ACGC activation was seen only when remembering a percept (more extensively and bilaterally when it was a facial diagram than when it was a color) but not when anticipating a response. These results reveal an ACGC dysfunction during choice anticipation in schizophrenia and suggest that it might underlie the foresight deficits seen in schizophrenic patients. Published by Elsevier Ireland Ltd. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA 90073 USA. MIRECC, VA Mental Illness VISN22, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Mapping Ctr, Los Angeles, CA 90095 USA. RP Quintana, J (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Room C8-222,760 Westwood Plaza, Los Angeles, CA 90024 USA. EM xquintan@ucla.edu FU NCRR NIH HHS [RR12169] NR 75 TC 25 Z9 26 U1 5 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 15 PY 2004 VL 132 IS 2 BP 117 EP 130 DI 10.1016/j.psychresns.2004.06.005 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 893WX UT WOS:000226752700003 PM 15598546 ER PT J AU Caetano, SC Hatch, JP Brambilla, P Sassi, RB Nicoletti, M Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC AF Caetano, SC Hatch, JP Brambilla, P Sassi, RB Nicoletti, M Mallinger, AG Frank, E Kupfer, DJ Keshavan, MS Soares, JC TI Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE depression; amygdala; hippocampus; superior temporal gyrus; temporal lobe; MRI; neuroimaging ID TEMPORAL-LOBE STRUCTURES; MOOD DISORDERS; BIPOLAR DISORDER; GERIATRIC DEPRESSION; VOLUME LOSS; ABNORMALITIES; UNIPOLAR; EPISODE; SCHIZOPHRENIA; ATROPHY AB Morphometric MRI studies suggest decreased hippocampal volumes in currently depressed patients. with conflicting findings for the amygdala. We studied these temporal lobe structures and superior temporal gyrus (STG) in patients with current and remitted major depression. We scanned 31 unmedicated depressed patients (21 currently depressed, 10 remitted) and 31 matched healthy controls with a 3D SPGR sequence in a 1.5 Tesla GE Signa Imaging System. There was a trend towards smaller left amygdala volumes in all depressed patients compared with healthy controls. We found significantly smaller hippocampal volumes bilaterally in currently depressed patients than in remitted patients. Furthermore. we found a statistically significant inverse correlation between length of illness and left hippocampus volumes and fight superior temporal gyrus volumes. Our finding of smaller hippocampi in currently depressed patients is consistent with the hypothesis that hypercortisolism could result in hippocampal neurotoxicity in major depression. A smaller hippocampal size may be more characteristic of the depressive state and not be present in remitted patients. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Univ Udine, Sect Psychiat, Dept Pathol, I-33100 Udine, Italy. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 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 NIMH NIH HHS [MH 30915, MH 01736] NR 41 TC 126 Z9 134 U1 1 U2 13 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC 15 PY 2004 VL 132 IS 2 BP 141 EP 147 DI 10.1016/j.psychresns.2004.08.002 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 893WX UT WOS:000226752700005 PM 15598548 ER PT J AU Green, MF Nuechterlein, KH AF Green, MF Nuechterlein, KH TI The MATRICS initiative: developing a consensus cognitive battery for clinical trials SO SCHIZOPHRENIA RESEARCH LA English DT Editorial Material C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Geffen Sch Med, 300 Med Plaza, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu; keithn@ucla.edu NR 10 TC 134 Z9 144 U1 7 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 1 EP 3 DI 10.1016/j.schres.2004.09.006 PG 3 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900001 PM 15531401 ER PT J AU Marder, SR Fenton, W AF Marder, SR Fenton, W TI Measurement and Treatment Research to Improve Cognition in Schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE functional outcome; functional capacity; cognition; schizophrenia ID NEUROCOGNITIVE DEFICITS AB The impairments in social and vocational outcome that are common in schizophrenia are strongly related to the severity of impaired neurocognition. This observation led to the initiation of The NIMH's Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, which supports the development of pharmacological agents to improve cognition in schizophrenia. MATRICS addresses barriers to drug development through a number of activities, including the development of a consensus battery for measuring cognition in schizophrenia; the development of a consensus regarding the most promising molecular targets that should be the focus of drug development; the use of a joint meeting with representatives from the industry, academia, NIMH, and the U.S. Food and Drug Administration (FDA) to clarify guidelines for the design of clinical trials for cognition enhancing agents; and finally, to assist NIMH in developing its research agenda in this area. (C) 2004 Published by Elsevier B.V. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90073 USA. W Los Angeles VA Healthcare Ctr, MIRECC 210A, VISN 22, Mental Illness Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. NIH, Bethesda, MD 20892 USA. RP Marder, SR (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM marder@ucla.edu NR 20 TC 202 Z9 213 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 5 EP 9 DI 10.1016/j.schres.2004.09.010 PG 5 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900002 PM 15531402 ER PT J AU Kern, RS Green, MF Nuechterlein, KH Deng, BH AF Kern, RS Green, MF Nuechterlein, KH Deng, BH TI NIMH-MATRICS survey on assessment of neurocognition in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE NIMH-MATRICS; neurocognition; schizophrenia AB The NIMH-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative requires, among other things, the establishment of a reliable, valid, and consensus-derived method of assessing cognition. The derived battery will provide a standardized way to assess the effects of cognition-enhancing agents across clinical trials. To this end, the first of six consensus-oriented conferences was held April 2003. The goals were twofold: (a) To select which cognitive constructs to measure in a consensus battery, and (b) to select which criteria to use in evaluating tests for inclusion in the battery. Based on consultation with experts on the RAND Panel Method, 74 experts were invited to participate in a pre-meeting survey to provide information relevant to decisions on the cognitive battery. The survey included sections on reliability, validity, test administration, norms and interpretation of tests, cognitive domains and their integration, battery duration, and overall importance of test qualities. For selection of cognitive targets, the results showed that experts ranked executive functions, attention/vigilance, memory processes, and problem-solving ability highest. For test qualities, the experts ranked test-retest reliability, good coverage of key individual cognitive constructs, and comparable alternate forms highest. This article presents the results of the pre-conference survey that was the first step in the RAND process towards development of the NIMH-MATRICS consensus battery to assess cognition in schizophrenia. (C) 2004 Elsevier B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, MIRECC 210A, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC 210A, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rkern@ucla.edu FU NIMH NIH HHS [MH22006] NR 10 TC 53 Z9 57 U1 10 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 11 EP 19 DI 10.1016/j.schres.2004.09.004 PG 9 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900003 PM 15531403 ER PT J AU Nuechterlein, KH Barch, DM Gold, JM Goldberg, TE Green, MF Heaton, RK AF Nuechterlein, KH Barch, DM Gold, JM Goldberg, TE Green, MF Heaton, RK TI Identification of separable cognitive factors in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognition; schizophrenia; factor analysis; neuropsychology; psychopharmacology ID CONTINUOUS PERFORMANCE-TEST; WORKING-MEMORY IMPAIRMENTS; NEUROPSYCHOLOGICAL DEFICITS; SOCIAL COGNITION; INFORMATION; DYSFUNCTION; DISORDERS; ATTENTION; BATTERY; 1ST-EPISODE AB One of the primary goals in the NIMH initiative to encourage development of new interventions for cognitive deficits in schizophrenia, Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS), has been to develop a reliable and valid consensus cognitive battery for use in clinical trials. Absence of such a battery has hampered standardized evaluation of new treatments and, in the case of pharmacological agents, has been an obstacle to FDA approval of medications targeting cognitive deficits in schizophrenia. A fundamental step in developing such a battery was to identify the major separable cognitive impairments in schizophrenia. As part of this effort, we evaluated the empirical evidence for cognitive performance dimensions in schizophrenia, emphasizing factor analytic studies. We concluded that seven separable cognitive factors were replicable across studies and represent fundamental dimensions of cognitive deficit in schizophrenia: Speed of Processing, Attention/Vigilance, Working Memory, Verbal Learning and Memory, Visual Learning and Memory, Reasoning and Problem Solving, and Verbal Comprehension. An eighth domain, Social Cognition, was added due to recent increased interest in this area and other evidence of its relevance for clinical trials aiming to evaluate the impact of potential cognitive enhancers on cognitive performance and functional outcome. Verbal Comprehension was not considered appropriate for a cognitive battery intended to be sensitive to cognitive change, due to its resistance to change. The remaining seven domains were recommended for inclusion in the MATRICS-NIMH consensus cognitive battery and will serve as the basic structure for that battery. These separable cognitive dimensions also have broader relevance to future research aimed at understanding the nature and structure of core cognitive deficits in schizophrenia. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA. Washington Univ, Dept Psychol, St Louis, MO USA. Univ Maryland Baltimore Cty, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. NIMH, Intramural Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Nuechterlein, KH (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 300 Med Plaza,Rm 2251, Los Angeles, CA 90095 USA. EM keithn@ucla.edu RI Barch, Deanna/G-8638-2013 FU NIMH NIH HHS [MH22006, MH66286] NR 67 TC 590 Z9 609 U1 15 U2 76 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 29 EP 39 DI 10.1016/j.schres.2004.09.007 PG 11 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900005 PM 15531405 ER PT J AU Green, MF Kern, RS Heaton, RK AF Green, MF Kern, RS Heaton, RK TI Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognition; schizophrenia; MATRICS ID PERSISTENT MENTAL-ILLNESS; QUALITY-OF-LIFE; NEUROCOGNITIVE DEFICITS; FOLLOW-UP; NEUROPSYCHOLOGICAL IMPAIRMENT; SCHIZOAFFECTIVE DISORDER; SOCIAL-BEHAVIOR; 1ST EPISODE; SCALE; SYMPTOMS AB It is generally accepted that cognitive deficits in schizophrenia are related to functional outcome. However, support for longitudinal relationships between cognition and functional outcome has not been as well documented. The current paper presents a review of 18 recently published longitudinal studies (minimum 6-month follow up) of the relationships between cognition and community outcome in schizophrenia. Results from these studies reveal considerable support for longitudinal associations between cognition and community outcome in schizophrenia. These studies demonstrate that cognitive assessment predict later functional outcome and provide a rationale for psychopharmacological interventions for cognitive deficits in schizophrenia. Although the relationships between cognition and community outcome are well-supported, it is clear that community functioning is also affected by a host of factors apart from cognition that are usually not considered in clinical trial studies (e.g., psychosocial rehabilitation and educational/vocational opportunities). In the second part of the paper, we consider intervening steps between cognitive performance measures and community outcome. These steps are apt to have important implications for clinical trials of cognition-enhancing agents in schizophrenia. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 300 Med Plaza,Rm 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu FU NIMH NIH HHS [MH22006] NR 48 TC 658 Z9 673 U1 4 U2 47 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC 15 PY 2004 VL 72 IS 1 BP 41 EP 51 DI 10.1016/j.schres.2004.09.009 PG 11 WC Psychiatry SC Psychiatry GA 886FI UT WOS:000226211900006 PM 15531406 ER PT J AU Bellamy, SL Yi, L Ryan, LM Lipsitz, S Canner, MJ Wright, R AF Bellamy, SL Yi, L Ryan, LM Lipsitz, S Canner, MJ Wright, R TI Analysis of clustered and interval censored data from a community-based study in asthma SO STATISTICS IN MEDICINE LA English DT Article DE clustering; censoring; over-dispersion; survival analysis; frailty ID SURVIVAL-DATA; INTERVENTION; TRIALS; MODELS AB Many authors in recent years have proposed extensions of familiar survival analysis methodologies to apply in dependent data settings, for example, when data are clustered or subject to repeated measures. However, these extensions have been considered largely in the context of right censored data. In this paper, we discuss a parametric frailty model for the analysis of clustered and interval censored failure time data. Details are presented for the specific case where the underlying time to event data follow a Weibull distribution. Maximum likelihood estimates will be obtained using commercially available software and the empirical efficiency of these estimators will be explored via a simulation study. We also discuss a score test to make inferences about the magnitude and significance of over-dispersion in clustered data settings. These methods will be illustrated using data from the East Boston Asthma Study. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19103 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Channing Labs, Boston, MA 02115 USA. RP Bellamy, SL (reprint author), Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, 629 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19103 USA. EM sbellamy@cceb.upenn.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIMH NIH HHS [R01-MH61892] NR 29 TC 24 Z9 25 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 2004 VL 23 IS 23 BP 3607 EP 3621 DI 10.1002/sim.1918 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 874HM UT WOS:000225341500004 PM 15534894 ER PT J AU Eguchi, H Knosalla, C Lan, P Cheng, J Diouf, B Wang, L Abe, M Schuurman, HJ Sachs, DH Sykes, M Cooper, DKC Yang, YG AF Eguchi, H Knosalla, C Lan, P Cheng, J Diouf, B Wang, L Abe, M Schuurman, HJ Sachs, DH Sykes, M Cooper, DKC Yang, YG TI T cells from presensitized donors fail to cause graft-versus-host disease in a pig-to-mouse xenotransplantation model SO TRANSPLANTATION LA English DT Article DE graft-versus-host disease; hematopoiesis; pigs; xenotransplantation ID PERIPHERAL-BLOOD LYMPHOCYTES; BONE-MARROW ENGRAFTMENT; MIXED CHIMERISM; XENOGENEIC BARRIER; SCID MICE; HEMATOPOIETIC CHIMERISM; TOLERANCE INDUCTION; PREPARATIVE REGIMEN; ALLOGRAFT TOLERANCE; NATURAL ANTIBODIES AB Background. The ability of T cells from pigs, the most suitable donors for clinical xenotransplantation, to induce graft-versus-host disease (GVHD) and to facilitate hematopoietic cell engraftment in highly disparate xenogeneic recipients remains unclear. In this article, the authors address these questions in a presensitized pig-to-mouse transplantation model using porcine cytokine-transgenic mice. Methods. Swine donors were presensitized by mouse skin grafting and boosted by the injection of mouse cells after the skin graft was rejected. Porcine peripheral blood mononuclear cells (PBMC) and splenocytes were collected at various times after mouse skin grafting, and their potential to induce GVHD and to facilitate donor hematopoietic cell engraftment in conditioned murine recipients was evaluated. Results. Presensitization of donor pigs resulted in marked enhancement of anti-mouse responses, as reflected in augmented anti-mouse mixed lymphocyte responses, cell-mediated cytotoxicity, and antibody production. However, injection of high numbers of PBMC and splenocytes (>1 x 10(8)) with bone marrow cells from the presensitized pigs failed to induce detectable GVHD or long-term chimerism in mice that were treated with depleting anti-T-cell and natural killer cell antibodies, cobra venom factor, medronate-liposomes, and 4 Gy of whole-body and 7 Gy of thymic irradiation. Histologic analysis revealed no mononuclear cell infiltration or GVHD-associated lesions in the liver, intestine, lungs, or skin of the mouse recipients. Furthermore, the recipient mice had no detectable T cells or anti-pig immunoglobulin G antibodies in the blood by 6 weeks after injection of porcine cells. Conclusion. These results demonstrate that porcine T-cell function is severely impaired in the xenogeneic murine microenvironment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Immerge Bio Therapeut Inc, Cambridge, MA USA. RP Yang, YG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-5202,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL54038]; NIAID NIH HHS [P01 AI45897] NR 42 TC 5 Z9 5 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 DEC 15 PY 2004 VL 78 IS 11 BP 1609 EP 1617 DI 10.1097/01.TP.0000142621.52211.79 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 879FQ UT WOS:000225702200007 PM 15591949 ER PT J AU Schnickel, GT Whiting, D Hsieh, GR Yun, JJ Fischbein, MP Fishbein, MC Yao, W Shfizadeh, A Ardehali, A AF Schnickel, GT Whiting, D Hsieh, GR Yun, JJ Fischbein, MP Fishbein, MC Yao, W Shfizadeh, A Ardehali, A TI CD8 lymphocytes are sufficient for the development of chronic rejection SO TRANSPLANTATION LA English DT Article DE transplantation; chronic rejection; CD8 lymphocyte ID CARDIAC ALLOGRAFT-REJECTION; PERFORIN-DEFICIENT MICE; NONOBESE DIABETIC MICE; T-CELL SUBSETS; IFN-GAMMA; IN-VIVO; FAS; ARTERIOSCLEROSIS; VASCULOPATHY; ACTIVATION AB Background. The role of CD8 lymphocytes, in chronic rejection or cardiac allograft vasculopathy (CAV), is incompletely understood. The purposes of this study were to determine whether CD8 lymphocytes, in the absence of CD4 lymphocytes, are capable of causing the intimal lesions of CAV; and if so, to define the effector mechanism(s) of CD8 lymphocytes. Methods. We modified a previously characterized major histocompatibility complex class II mismatched murine model of CAV. Wild-type CD8 lymphocytes were transferred to nude mice followed by heterotopic heart transplantation. Recipient mice were then treated with a CD40 activating antibody, which is known to provide help for CD8 lymphocyte activation, in the absence of CD4 lymphocytes. Donor hearts were harvested on day 40 posttransplantation and analyzed for cellular infiltrates and intimal thickening. In separate experiments, isolated perforin -/-, Fas ligand (FasL) -/-, and interferon (IFN)-gamma -/- CD8 lymphocytes were transferred to nude mice followed by identical experimented protocol. Results. With adaptive transfer of wild-type CD8 lymphocytes, the donor hearts were infiltrated with activated CD8 lymphocytes and displayed significant intimal lesions. Adoptive transfer of perforin -/- and FasL -/- CD8 lymphocytes to nude mice resulted in similar patterns of CD8 lymphocyte infiltration and similar severity of intimal lesions. The donor hearts from IFN-gamma -/- CD8 lymphocyte reconstituted recipients displayed minimal intimal lesions, although CD8 lymphocytes were present in the allografts. Conclusions. Unprimed CD8 lymphocytes in the absence of CD4 lymphocytes can cause intimal lesions of CAV. CD8 lymphocytes production of IFN-gamma, but not the perforin or the FasL-mediated cytotoxicity, is the critical step in the development of intimal lesions. C1 Univ Calif Los Angeles, Ctr Med, Div Cardiothorac Surg, David Geffen Sch Med,Dept Surg, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Surg, Div Cardiac Surg, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. RP Ardehali, A (reprint author), Univ Calif Los Angeles, Ctr Med, Div Cardiothorac Surg, David Geffen Sch Med,Dept Surg, 62-18c CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM aardehali@mednet.ucla.edu OI Schnickel, Gabriel/0000-0003-4392-2200 NR 34 TC 15 Z9 18 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 DEC 15 PY 2004 VL 78 IS 11 BP 1634 EP 1639 DI 10.1097/01.TP.0000141362.33931.40 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 879FQ UT WOS:000225702200010 PM 15591952 ER PT J AU Miura, A Sajan, MP Standaert, ML Bandyopadhyay, G Kahn, CR Farese, RV AF Miura, A Sajan, MP Standaert, ML Bandyopadhyay, G Kahn, CR Farese, RV TI Insulin substrates 1 and 2 are corequired for activation of atypical protein kinase C and Cbl-dependent phosphatidylinositol 3-kinase during insulin action in immortalized brown adipocytes SO BIOCHEMISTRY LA English DT Article ID STIMULATED GLUT4 TRANSLOCATION; GLUCOSE-TRANSPORT; 3T3-L1 ADIPOCYTES; RECEPTOR SUBSTRATE-1; TYROSINE PHOSPHORYLATION; RAT ADIPOCYTES; PKC-ZETA; LAMBDA; 3T3/L1; IRS-1 AB Phosphatidylinositol 3-kinase (PI3K)-dependent activation of atypical protein kinase C (aPKC) is required for insulin-stimulated glucose transport. Although insulin receptor substrate-1 (IRS-1) and IRS-2, among other factors, activate PI3K, there is little information on the relative roles of IRS-1 and IRS-2 during aPKC activation by insulin action in specific cell types. Presently, we have used immortalized brown adipocytes in which either IRS-1 or IRS-2 has been knocked out by recombinant methods to examine IRS-1 and IRS-2 requirements for activation of aPKC. We have also used these adipocytes to see if IRS-1 and IRS-2 are required for activation of Cbl, which is required for insulin-stimulated glucose transport and has been found to function upstream of both PI3K/aPKC and Crk during thiazolidinedione action in 3T3/L1 adipocytes [Miura et al. (2003) Biochemistry 42, 14335]. In brown adipocytes in which either IRS-1 or IRS-2 was knocked out, insulin-induced increases in aPKC activity and glucose transport were markedly diminished. These effects of insulin on aPKC and glucose transport were fully restored by retroviral-mediated expression of IRS-1 or IRS-2 in their respective knockout cells. Knockout of IRS-1 or IRS-2 also inhibited insulin-induced increases in Cbl binding to the p85 subunit of PI3K, which, along with IRS-1/2, may be required for activation of PI3K, aPKC, and glucose transport during insulin action in 3T3/L1 adipocytes. These findings provide evidence that directly links both IRS-1 and IRS-2 to aPKC activation in immortalized brown adipocytes, and further suggest that IRS-1 and IRS-2 are required for the activation of Cbl/PI3K during insulin action in these cells. C1 Univ S Florida, Coll Med, James A Haley Vet Hosp, Res Serv, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Farese, RV (reprint author), Univ S Florida, Coll Med, James A Haley Vet Hosp, Res Serv, Tampa, FL 33612 USA. EM rfarese@hsc.usf.edu RI Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [DK33201, DK-38079-09A1, DK55545, R01 DK065969] NR 29 TC 13 Z9 13 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 14 PY 2004 VL 43 IS 49 BP 15503 EP 15509 DI 10.1021/bi049221y PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878UJ UT WOS:000225672300021 PM 15581362 ER PT J AU Lindenfeld, JA Miller, GG Shakar, SF Zolty, R Lowes, BD Wolfel, EE Mestroni, L Page, RL Kobashigawa, J AF Lindenfeld, JA Miller, GG Shakar, SF Zolty, R Lowes, BD Wolfel, EE Mestroni, L Page, RL Kobashigawa, J TI Drug therapy in the heart transplant recipient - Part I: Cardiac rejection and immunosuppressive drugs SO CIRCULATION LA English DT Article DE transplantation; immune system; rejection ID RENAL-ALLOGRAFT RECIPIENTS; MONOCLONAL-ANTIBODY OKT3; ACUTE CELLULAR REJECTION; ANTITHYMOCYTE GLOBULIN; HUMORAL REJECTION; ORGAN-TRANSPLANTATION; INTERNATIONAL-SOCIETY; LUNG-TRANSPLANTATION; INDUCTION THERAPY; CONTROLLED TRIAL C1 Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Ctr Womens Hlth Res, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Lindenfeld, JA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Cardiol, 4200 E 9th Ave B-130, Denver, CO 80262 USA. EM joann.lindenfeld@UCHSC.edu OI Lowes, Brian/0000-0002-5919-2540; Mestroni, Luisa/0000-0003-1116-2286 NR 50 TC 65 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 14 PY 2004 VL 110 IS 24 BP 3734 EP 3740 DI 10.1161/01.CIR.0000149745.83186.89 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 879HI UT WOS:000225706600019 PM 15596559 ER PT J AU Fossale, E Wolf, P Espinola, JA Lubicz-Nawrocka, T Teed, AM Gao, HL Rigamonti, D Cattaneo, E MacDonald, ME Cotman, SL AF Fossale, E Wolf, P Espinola, JA Lubicz-Nawrocka, T Teed, AM Gao, HL Rigamonti, D Cattaneo, E MacDonald, ME Cotman, SL TI Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis SO BMC NEUROSCIENCE LA English DT Article ID UNDERLYING BATTEN-DISEASE; CATHEPSIN-D; LYSOSOMAL PH; CLN3 PROTEIN; TRANSPORT; MUTATION AB Background: JNCL is a recessively inherited, childhood-onset neurodegenerative disease most-commonly caused by a similar to1 kb CLN3 mutation. The resulting loss of battenin activity leads to deposition of mitochondrial ATP synthase, subunit c and a specific loss of CNS neurons. We previously generated Cln3(Deltaex7/8) knock-in mice, which replicate the common JNCL mutation, express mutant battenin and display JNCL-like pathology. Results: To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3(Deltaex7/8) precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced. Conclusions: These findings reveal that battenin is required for intracellular membrane trafficking and mitochondrial function. Moreover, these deficiencies are likely to be early events in the JNCL disease process and may particularly impact neuronal survival. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA USA. Univ Milan, Dept Pharmacol Sci, Milan, Italy. Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy. RP Cotman, SL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. EM efossale@partners.org; pwolf@wellesley.edu; espinola@helix.mgh.harvard.edu; quisto@aol.com; ateed@mail.med.upenn.edu; gaohanlin6@yahoo.com.cn; dorotea.rigamonti@unimi.it; elena.cattaneo@unimi.it; macdonam@helix.mgh.harvard.edu; cotman@helix.mgh.harvard.edu FU NINDS NIH HHS [R01 NS033648, NS 33648] NR 29 TC 68 Z9 69 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD DEC 10 PY 2004 VL 5 AR 57 DI 10.1186/1471-2202-5-57 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 891UN UT WOS:000226606600001 PM 15588329 ER PT J AU Chen, K Mehta, JL Li, DY Joseph, L Joseph, J AF Chen, K Mehta, JL Li, DY Joseph, L Joseph, J TI Transforming growth factor beta receptor endoglin is expressed in cardiac fibroblasts and modulates profibrogenic actions of angiotensin II SO CIRCULATION RESEARCH LA English DT Article DE angiotensin II; collagen; endoglin; fibroblasts; remodeling ID ARTERY ENDOTHELIAL-CELLS; UP-REGULATION; MATRIX METALLOPROTEINASES; COLLAGEN PRODUCTION; SIGNALING PATHWAYS; GENE-EXPRESSION; FIBROSIS; HEART; FACTOR-BETA(1); MYOFIBROBLASTS AB Angiotensin II (Ang II) is a powerful mediator of adverse cardiac remodeling and fibrosis. However, the mechanisms of Ang II - induced myocardial fibrosis remain to be clarified. We postulated that Ang II alters transforming growth factor beta (TGF-beta) receptor expression, specifically that of endoglin, and thereby modulates cardiac fibroblast (CF) collagen metabolism. Experiments were conducted using CF from adult Sprague Dawley rats to determine the expression of TGF-beta(1) receptors including endoglin, and the role of Ang II type 1 (AT(1)) and type 2 (AT(2)) receptors, and MAPK p42/44 in this process. The functional role of endoglin in modulating Ang II effects on matrix metalloproteinase-1 (MMP-1) and type I collagen expression was also analyzed. Endoglin gene and protein expression were consistently identified in quiescent CFs. Ang II increased the expression of endoglin mRNA and protein in a concentration and time-dependent manner, with no effect on TGF-beta receptors I and II expression. This effect was AT1 receptor mediated, because AT1 receptor antagonists valsartan, candesartan, and losartan inhibited Ang II - induced endoglin expression, whereas the AT2 receptor antagonist PD123319 had no effect. MAPKp42/44 inhibition attenuated Ang II - induced endoglin expression. Ang II - induced decrease in MMP-1 protein expression and increase in type I collagen protein expression were both blocked by a specific endoglin antibody. Hence, our results indicate that endoglin is upregulated in CFs by Ang II via the AT1 receptor and modulates profibrotic effects of Ang II. These findings provide novel insights into Ang II - induced cardiac remodeling. C1 Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. VA Boston Healthcare Syst, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Joseph, J (reprint author), VA Boston Healthcare Syst, Cardiol Sect 111, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM jacob.joseph@med.va.gov NR 49 TC 87 Z9 102 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC 10 PY 2004 VL 95 IS 12 BP 1167 EP 1173 DI 10.1161/01.RES.0000150369.68826.2f PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 878IT UT WOS:000225641000005 PM 15539634 ER PT J AU Ishiguro, K Cao, ZF Lopez-Ilasca, M Ando, T Xavier, R AF Ishiguro, K Cao, ZF Lopez-Ilasca, M Ando, T Xavier, R TI Wave2 activates serum response element via its VCA region and functions downstream of Rac SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE signal transduction; serum response element; actin polymerization; rho GTPase; WAVE ID NF-KAPPA-B; ALDRICH-SYNDROME PROTEIN; FAMILY PROTEINS; ACTIN DYNAMICS; CELL-MIGRATION; NUCLEAR-FACTOR; WASP; SRF; IDENTIFICATION; TRANSCRIPTION AB WAVE2 is a member of the WASP/WAVE family of protein effectors of actin reorganization and cell movement. In this report, we demonstrate that WAVE2 overexpression induces serum response element (SRE) activation through serum response factor. A WAVE2 mutant lacking the VCA region did not induce SIZE activation and actin polymerization. WAVE2-induced SRE activation was blocked by exposure of cells to Latrunculin A, or overexpression of actin mutant R62D. The DeltaVCA mutant inhibited Rae V12-induced SRE activation, suggesting that WAVE2 lies downstream of Rac. Similar deletion of the VCA domain of WASP attenuated Cdc42 V12-mediated SIZE activation, suggesting that WAVE2 acts in relation to Rae as WASP acts in relation to Cdc42. WAVE2 overexpression did not activate NF-kappaB. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Nagoya Univ, Grad Sch Med, Showa Ku, Nagoya, Aichi 4668550, Japan. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Xavier, R (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu OI Ishiguro, Kazuhiro/0000-0003-1776-2805 NR 42 TC 3 Z9 3 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 DEC 10 PY 2004 VL 301 IS 2 BP 331 EP 337 DI 10.1016/j.yexcr.2004.09.003 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 873DY UT WOS:000225260800021 PM 15530867 ER PT J AU Goel, A Arnold, CN Tassone, P Chang, DK Niedzwiecki, D Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR AF Goel, A Arnold, CN Tassone, P Chang, DK Niedzwiecki, D Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR TI Epigenetic inactivation of RUNX3 in microsatellite unstable sporadic colon cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE RUNX3; methylation; colon cancer ID HUMAN COLORECTAL-CANCER; GASTRIC-CANCER; CELL-LINES; FUNCTIONAL COOPERATION; METHYLATION STATUS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; INSTABILITY; TUMORIGENESIS; PEBP2/CBF AB Runt domain transcription factors are important targets of TGF-beta superfamily proteins and play a crucial role in mammalian development. Three mammalian runt-related genes, RUNX1, RUNX2 and RUNX3, have been described. RUNX3 has been shown to be a putative tumor suppressor gene localized to chromosome Ip36, a region showing frequent loss of heterozygosity events in colon, gastric, breast and ovarian cancers. Because of the important role of TGF-beta signaling in the human colon, we hypothesized that RUNX3 may serve as a key tumor suppressor in human colon cancers and colon cancer-derived cell lines. We examined RUNX3 expression and the frequency of RUNX3 promoter hypermethylation in 17 colon cancer cell lines and 91 sporadic colorectal cancers. Semiquantitative analysis of RUNX3 transcripts was performed by RT-PCR and de novo methylation of the RUNX3 promoter was studied by a methylation-specific PCR (MSP) assay. Nineteen of 91 informative tumors (21%) and 11 of 17 (65%) colon cancer cell lines exhibited hypermethylation of the RUNX3 promoter. Interestingly, RUNX3 promoter hypermethylation was more common in tumors exhibiting high frequency of microsatellite instability (MSI-H) (33% of MSI-H vs. 12% of MSI-L/MSS tumors; p = 0.012). Hypermethylation of the RUNX3 promoter correlated with loss of mRNA transcripts in all cell lines. RUNX3 promoter methylation was reversed and its expression restored in SW48 and HCT15 colon cancer cells after treatment with the demethylating agent 5-aza-2'-deoxycytidine, indicating that loss of expression is caused by epigenetic inactivation in colon carcinogenesis. This is the first demonstration of frequent de novo hypermethylation of the RUNX3 promoter in sporadic colon cancers. The significant association of RUNX3 promoter hypermethylation with MSI-H colon cancers suggests that RUNX3 is a novel target of methylation, along with the hMLHI gene, in the evolution of MSI-H colorectal cancers. (C) 2004 Wiley-Liss, Inc. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Comprehens Canc, La Jolla, CA 92093 USA. Duke Univ, CALGB Stat Ctr, Durham, NC USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Boland, CR (reprint author), Baylor Univ, Med Ctr, Hoblitzelle,Suite H-250,3500 Gaston Ave, Dallas, TX 75246 USA. EM Rickbo@BaylorHealth.Edu FU NCI NIH HHS [CA04326, CA02599, CA03927, CA04457, CA08025, CA11789, CA12046, CA12449, CA16450, CA21060, CA26806, CA31946, CA31983, CA32291, CA33601, CA37135, CA41287, CA45808, CA47555, CA47559, CA47642, CA60138, CA74811, CA77658, R01-CA 72851] NR 32 TC 75 Z9 77 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 10 PY 2004 VL 112 IS 5 BP 754 EP 759 DI 10.1002/ijc.20472 PG 6 WC Oncology SC Oncology GA 867EJ UT WOS:000224824800005 PM 15386381 ER PT J AU Yu, DH Khan, E Khaleque, MA Lee, J Laco, G Kohlhagen, G Kharbanda, S Cheng, YC Pommier, Y Bharti, A AF Yu, DH Khan, E Khaleque, MA Lee, J Laco, G Kohlhagen, G Kharbanda, S Cheng, YC Pommier, Y Bharti, A TI Phosphorylation of DNA topoisomerase I by the c-Abl tyrosine kinase confers camptothecin sensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVE-SITE TYROSINE; N-TERMINAL DOMAIN; CATALYTIC-ACTIVITY; APOPTOTIC RESPONSE; IONIZING-RADIATION; CLEAVAGE COMPLEXES; ANTITUMOR DRUGS; STRESS-RESPONSE; CYTO-TOXICITY; STRAND BREAKS AB DNA topoisomerase I ( topo I) is involved in the regulation of DNA supercoiling, gene transcription, recombination, and DNA repair. The anticancer agent camptothecin specifically targets topo I. The mechanisms responsible for the regulation of topo I in cells, however, are not known. This study demonstrates that c-Abl-dependent phosphorylation up-regulates topo I activity. The c-Abl SH3 domain bound directly to the N-terminal region of topo I. The results demonstrate that c-Abl phosphorylated topo I at Tyr(268) in core subdomain II. c-Abl-mediated phosphorylation of topo I Tyr(268) in vitro and in cells conferred activation of the topo I isomerase function. Moreover, activation of c-Abl by treatment of cells with ionizing radiation was associated with c-Abl-dependent phosphorylation of topo I and induction of topo I activity. The functional significance of the c-Abl/topo I interaction is supported by the findings that (i) mutant topo I(Y268F) exhibited loss of c-Abl-induced topo I activity, and (ii) c-Abl(-/-) cells were deficient in the accumulation of protein-linked DNA breaks. In addition, loss of topo I phosphorylation in c-Abl-deficient cells conferred resistance to camptothecin-induced apoptosis. These findings collectively support a model in which c-Abl-mediated phosphorylation of topo I is functionally important to topo I activity and sensitivity to topo I poisons. C1 Boston Univ, Sch Med, Dept Med, Ctr Mol Stress Response, Boston, MA 02118 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Bharti, A (reprint author), Boston Univ, Sch Med, Dept Med, Ctr Mol Stress Response, 650 Albany St,EBRC-311, Boston, MA 02118 USA. EM Bharti@bu.edu FU NCI NIH HHS [CA55241] NR 91 TC 20 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 DEC 10 PY 2004 VL 279 IS 50 BP 51851 EP 51861 DI 10.1074/jbc.M404396200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400018 PM 15448168 ER PT J AU Park, KM Kim, JI Ahn, Y Bonventre, AJ Bonventre, JV AF Park, KM Kim, JI Ahn, Y Bonventre, AJ Bonventre, JV TI Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; VASCULAR ENDOTHELIAL-CELLS; INDUCED FUNCTIONAL INJURY; MAPK KINASE ACTIVATION; REPERFUSION INJURY; SEX-HORMONES; L-ARGININE; IN-VITRO; MYOCARDIAL-ISCHEMIA; MONOCYTE ADHESION AB Female mice are much more resistant to ischemia/reperfusion (I/R)-induced kidney injury when compared with males. Although estrogen administration can partially reduce kidney injury associated with I/R, we demonstrated that the presence of testosterone, more than the absence of estrogen, plays a critical role in gender differences in susceptibility of the kidney to ischemic injury. Testosterone administration to females increases kidney susceptibility to ischemia. Dihydrotestosterone, which can not be aromatized to estrogen, has effects equal to those of testosterone. Castration reduces the I/R-induced kidney injury. In contrast, ovariectomy does not affect kidney injury induced by ischemia in females. Testosterone reduces ischemia-induced activation of nitric oxide synthases (NOSs) and Akt and the ratio of extracellular signal related kinase (ERK) to c-jun N-terminal kinase (JNK) phosphorylation. Pharmacological (N-omega-nitro-L-arginine) or genetic ( endothelial NOS or inducible NOS) inhibition of NOSs in females enhances kidney susceptibility to ischemia. Nitric oxide increases Akt phosphorylation and protects Madin-Darby canine kidney epithelial cells from oxidant stress. Antagonists of androgen or estrogen receptors do not affect the gender differences. In conclusion, testosterone inhibits the post-ischemic activation of NOSs and Akt and the ratio of ERK to JNK phosphorylation through non-androgen receptor-medicated mechanisms, leading to increased inflammation and increased functional injury to the kidney. These findings provide a new paradigm for the design of therapies for ischemia/reperfusion injury and may be important to our understanding of the pathophysiology of acute renal failure in pregnancy where plasma androgen levels are elevated. C1 Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Kyungpook Natl Univ, Sch Med, Dept Anat, Taegu 700422, South Korea. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Renal Div, Boston, MA 02115 USA. RP Bonventre, JV (reprint author), Harvard Inst Med, 4 Blackfan Circle, Boston, MA 02115 USA. EM joseph_bonventre@hms.harvard.edu FU NIDDK NIH HHS [DK 38452, DK 39773, DK46267]; NINDS NIH HHS [NS 10828] NR 50 TC 137 Z9 149 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 10 PY 2004 VL 279 IS 50 BP 52282 EP 52292 DI 10.1074/jbc.M407629200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400069 PM 15358759 ER PT J AU Yokokura, T Dresnek, D Huseinovic, N Lisi, S Abdelwahid, E Bangs, P White, K AF Yokokura, T Dresnek, D Huseinovic, N Lisi, S Abdelwahid, E Bangs, P White, K TI Dissection of DIAP1 functional domains via a mutant replacement strategy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE-PROTEASE OMI/HTRA2; DROSOPHILA CASPASE DRONC; PROGRAMMED CELL-DEATH; APOPTOSIS PROTEINS; IAP PROTEINS; GRIM-REAPER; REGULATING APOPTOSIS; STRUCTURAL BASIS; LIGASE ACTIVITY; HID AB Inhibitor of apoptosis proteins (IAPs) act as endogenous inhibitors of active caspases. Drosophila IAP1 (DIAP1) activity is required to keep cells from undergoing apoptosis. The central cell death regulators Reaper and Hid induce apoptosis very rapidly by inhibiting DIAP1 function. We have developed a system for replacing endogenous DIAP1 with mutant forms of the protein, allowing us to examine the roles of various domains of the protein in living and dying cells. We found that DIAP1 is cleaved by a caspase early after the initiation of apoptosis. This cleavage is required for DIAP1 degradation, but Rpr and Hid can still initiate apoptosis in the absence of cleavage. The cleavage of DIAP1 promotes DIAP1 degradation in a manner dependent on the function of the ubiquitin ligase function of the DIAP1 ring domain. This ring domain function is required for Hid-induced apoptosis. We propose a model that synthesizes our data with those of other laboratories and provide a consistent model for DIAP1 function in living and dying cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kristin.white@CBRC2.MGH.Harvard.edu RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [GM55568] NR 52 TC 33 Z9 33 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 DEC 10 PY 2004 VL 279 IS 50 BP 52603 EP 52612 DI 10.1074/jbc.M409691200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 876JT UT WOS:000225493400107 PM 15371434 ER PT J AU Mehlmann, LM Saeki, Y Tanaka, S Brennan, TJ Evsikov, AV Pendola, FL Knowles, BB Eppig, JJ Jaffe, LA AF Mehlmann, LM Saeki, Y Tanaka, S Brennan, TJ Evsikov, AV Pendola, FL Knowles, BB Eppig, JJ Jaffe, LA TI The G(s)-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes SO SCIENCE LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; MOLECULAR-CLONING; MOUSE OOCYTES; G(S) PROTEIN; MATURATION; KINASE; PHOSPHORYLATION; LOCALIZATION; ACTIVATION AB Mammalian oocytes are held in prophase arrest by an unknown signal from the surrounding somatic tells. Here we show that the orphan G(s)-linked receptor GPR3, which is localized in the oocyte, maintains this arrest. Oocytes from Gpr3 knockout mice resume meiosis within antral follicles, independently of an increase in luteinizing hormone, and this phenotype can be reversed by injection of Gpr3 RNA into the oocytes. Thus, the GPR3 receptor is a link in communication between the somatic cells and oocyte of the ovarian follicle and, is crucial for the regulation of meiosis. C1 Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Deltagen Inc, San Carlos, CA 94070 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Mehlmann, LM (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. EM lmehlmann@neuron.uchc.edu; ljaffe@neuron.uchc.edu RI Evsikov, Alexei/E-2577-2012; Tanaka, Shigeru/O-3908-2015 NR 24 TC 181 Z9 190 U1 0 U2 5 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 DEC 10 PY 2004 VL 306 IS 5703 BP 1947 EP 1950 DI 10.1126/science.1103974 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879DC UT WOS:000225695600048 PM 15591206 ER PT J AU Corey, DP Garcia-Anoveros, J Holt, JR Kwan, KY Lin, SY Vollrath, MA Amalfitano, A Cheung, ELM Derfler, BH Duggan, A Geleoc, GSG Gray, PA Hoffman, MP Rehm, HL Tamasauskas, D Zhang, DS AF Corey, DP Garcia-Anoveros, J Holt, JR Kwan, KY Lin, SY Vollrath, MA Amalfitano, A Cheung, ELM Derfler, BH Duggan, A Geleoc, GSG Gray, PA Hoffman, MP Rehm, HL Tamasauskas, D Zhang, DS TI TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells SO NATURE LA English DT Article ID ION CHANNELS; INNER-EAR; MECHANOELECTRICAL TRANSDUCTION; MECHANOTRANSDUCER CHANNEL; TIP LINKS; ADAPTATION; MUTATIONS; GENE; CADHERIN-23; ADENOVIRUS AB Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP ( transient receptor potential) ion channels as candidates and find one, TRPA1 ( also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Inst Neurosci, Dept Anesthesiol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Inst Neurosci, Dept Physiol, Chicago, IL 60611 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Otolaryngol, Charlottesville, VA 22908 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Partners Genome Ctr, Mol Med Lab, Cambridge, MA 02139 USA. Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27705 USA. NIDCR, Matrix & Morphogenesis Unit, CDBRB, NIH, Bethesda, MD 20892 USA. RP Corey, DP (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM dcorey@hms.harvard.edu OI Corey, David/0000-0003-4497-6016 NR 42 TC 412 Z9 458 U1 4 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 9 PY 2004 VL 432 IS 7018 BP 723 EP 730 DI 10.1038/nature03066 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877UE UT WOS:000225597200040 PM 15483558 ER PT J AU Kiepiela, P Leslie, AJ Honeyborne, I Ramduth, D Thobakgale, C Chetty, S Rathnavalu, P Moore, C Pfafferott, KJ Hilton, L Zimbwa, P Moore, S Allen, T Brander, C Addo, MM Altfeld, M James, I Mallal, S Bunce, M Barber, LD Szinger, J Day, C Klenerman, P Mullins, J Korber, B Coovadia, HM Walker, BD Goulder, PJR AF Kiepiela, P Leslie, AJ Honeyborne, I Ramduth, D Thobakgale, C Chetty, S Rathnavalu, P Moore, C Pfafferott, KJ Hilton, L Zimbwa, P Moore, S Allen, T Brander, C Addo, MM Altfeld, M James, I Mallal, S Bunce, M Barber, LD Szinger, J Day, C Klenerman, P Mullins, J Korber, B Coovadia, HM Walker, BD Goulder, PJR TI Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA SO NATURE LA English DT Article ID CLASS-I MOLECULES; IMMUNE-RESPONSES; VIRUS; AIDS; TRANSMISSION; PROGRESSION; INFECTION; ALLELES; ADVANTAGE; EVOLUTION AB The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8(+) T cells(1-3). HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8(+) T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8(+) T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8(+) T-cell activity(4,5). In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8(+) T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles(6-8). The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design. C1 Univ KwaZuluNatal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4015 Durban, South Africa. Nuffield Dept Med, Dept Paediat, Oxford OX1 3SY, England. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia. Murdoch Univ, Royal Perth Hosp, Perth, WA 6000, Australia. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Dynal Biotech Ltd, Wirral CH62 3QL, Merseyside, England. Royal Free Hosp, Anthony Nolan Res Inst, London NW3 2QG, England. Santa Fe Inst, Santa Fe, NM 87501 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Goulder, PJR (reprint author), Univ KwaZuluNatal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, 719 Umbilo Rd, ZA-4015 Durban, South Africa. EM philip.goulder@ndm.ox.ac.uk RI Day, Cheryl/J-9844-2012; Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Korber, Bette/0000-0002-2026-5757 NR 28 TC 479 Z9 496 U1 5 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 9 PY 2004 VL 432 IS 7018 BP 769 EP 774 DI 10.1038/nature03113 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 877UE UT WOS:000225597200052 PM 15592417 ER PT J AU Penson, RT Sahani, D Bell, DA AF Penson, RT Sahani, D Bell, DA TI Case 37-2004: A 52-year-old woman with postmenopausal bleeding and a cystic ovarian mass - Right ovary: papillary serous cystadenocarcinoma, grade 2 to 3 of 3, arising as a polypoid intracystic mass in a serous tumor containing benign, typical borderline, and micropapillary borderline areas. Left ovary: serous borderline tumor, typical type, small. Uterus, omentum, and lymph nodes: no evidence of cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ADJUVANT CHEMOTHERAPY; NEOPLASM TRIAL; STAGE-I; CRIBRIFORM PATTERNS; CARCINOMA; CISPLATIN; PACLITAXEL; WOMEN; CYCLOPHOSPHAMIDE C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Ctr Canc, Boston, MA 02114 USA. NR 39 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 DEC 9 PY 2004 VL 351 IS 24 BP 2531 EP 2538 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 877TE UT WOS:000225593100010 PM 15590956 ER PT J AU Lu, QY Jin, YS Zhang, QF Zhang, ZF Heber, D Go, VLW Li, FP Rao, JY AF Lu, QY Jin, YS Zhang, QF Zhang, ZF Heber, D Go, VLW Li, FP Rao, JY TI Ganoderma lucidum extracts inhibit growth and induce actin polymerization in bladder cancer cells in vitro SO CANCER LETTERS LA English DT Article DE Ganoderma lucidum; chemoprevention; bladder cancer; actin polymerization ID PROSTATE CARCINOMA-CELLS; CELLULAR-TRANSFORMATION; F-ACTIN; FUNGAL POLYSACCHARIDES; STRUCTURAL EXAMINATION; ANTITUMOR-ACTIVITY; SPORES; DIFFERENTIATION; CYTOSKELETON; DISRUPTION AB This study was conducted to investigate chemopreventive effects of Ganoderma lucidum using a unique in vitro human urothelial cell (HUC) model consisted of HUC-PC cells and MTC-11 cells. Ethanol and water extracts of fruiting bodies and spores of the G. lucidum were used to examine growth inhibition, actin polymerization status, and impact of actin remodeling on cell migration and adhesion. Results showed that ethanol extracts had a stronger growth inhibition effect than water extracts. Cell cycle analysis showed that the growth inhibition effect was associated with G(2)/M arrest. At non-cytotoxic concentrations (40-80 mug/ml), these extracts induced actin polymerization, which in turn inhibited carcinogen 4-aminobiphenyl induced migration in both cell lines. The increased actin polymerization was associated with increased stress fibers and focal adhesion complex formation, however, expression of matrix metalloproteinase-2 and focal adhesion kinase (total and phospholated) were unchanged, which suggests that other mechanisms may be involved. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Ctr Human Nutr, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rao, JY (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Box 951732, Los Angeles, CA 90095 USA. EM jrao@mednet.ucla.edu FU NCCIH NIH HHS [AT00151]; NCI NIH HHS [P50 CA90833, U01 CA96116] NR 41 TC 63 Z9 68 U1 3 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 8 PY 2004 VL 216 IS 1 BP 9 EP 20 DI 10.1016/j.canlet.2004.06.022 PG 12 WC Oncology SC Oncology GA 871HD UT WOS:000225119900002 PM 15500944 ER PT J AU Arango, NA Pearson, EJ Donahoe, PK Teixeira, J AF Arango, NA Pearson, EJ Donahoe, PK Teixeira, J TI Genomic structure and expression analysis of the mouse testis-specific ribbon protein (Trib) gene SO GENE LA English DT Article DE gonad; spermatogenesis; meiosis; microtubule ID SEA-URCHIN EGGS; FLAGELLAR MICROTUBULES; CHROMOSOME DYNAMICS; SPERM FLAGELLA; GAMMA-TUBULIN; IN-VITRO; CENTROSOME; COMPONENTS; FERTILIZATION; CENTRIOLES AB During our analyses of genes required for the development and function of the mouse gonads, we identified a novel testis-specific mRNA, transcribed from a gene that we have named testis-specific ribbon protein (Trib). In the mouse, Trib is located on chromosome 15, overlapping with and transcribed in the opposite orientation of the meiosis specific gene Smc1beta. The deduced amino acid sequence of testis ribbon (TRIB) protein is highly conserved between human, mouse, and rat and contains the ribbon motifs found in the largely uncharacterized microtubule ribbon protein ribbon43a (RIB43A). We show by Northern blot analyses and reverse transcription-polymerase chain reaction (RT-PCR) that Trib mRNA is specifically expressed in the adult testis. In situ hybridization indicates that Trib is expressed solely in germ cells during the leptotene-pachytene stages of spermatogenesis. The high level of evolutionary conservation and the cellular and temporal expression suggest that Trib may be required for mouse spermatogenesis and male fertility. Here, we describe the genomic structure and expression profile of mouse Trib and compare its homology with other ribbon proteins. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs WRN1024, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Arango, NA (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs WRN1024, 32 Fruit St, Boston, MA 02114 USA. EM narango@partners.org FU NICHD NIH HHS [F32 HD43539, U54-HD28138] NR 22 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 8 PY 2004 VL 343 IS 1 BP 221 EP 227 DI 10.1016/j.gene.2004.09.014 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 879PC UT WOS:000225728700022 PM 15563848 ER PT J AU Schon, K Hasselmo, ME LoPresti, ML Tricarico, MD Stern, CE AF Schon, K Hasselmo, ME LoPresti, ML Tricarico, MD Stern, CE TI Persistence of parahippocampal representation in the absence of stimulus input enhances long-term encoding: A functional magnetic resonance imaging study of subsequent memory after a delayed match-to-sample task SO JOURNAL OF NEUROSCIENCE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Neuroscience CY NOV 08-12, 2003 CL NEW ORLEANS, LA SP Soc Neurosci DE memory; parahippocampal; neuroimaging; medial temporal lobe; delayed match to sample; computational modeling ID MEDIAL TEMPORAL-LOBE; EVENT-RELATED FMRI; WORKING-MEMORY; ENTORHINAL CORTEX; HIPPOCAMPAL-FORMATION; SPATIAL NAVIGATION; RECOGNITION MEMORY; PREFRONTAL CORTEX; FRONTAL-CORTEX; BRAIN ACTIVITY AB Recent theoretical models based on cellular processes in parahippocampal structures show that persistent neuronal spiking in the absence of stimulus input is important for encoding. The goal of this study was to examine in humans how sustained activity in the parahippocampal gyrus may underlie long-term encoding as well as active maintenance of novel information. The relationship between long-term encoding and active maintenance of novel information during brief memory delays was studied using functional magnetic resonance imaging (fMRI) in humans performing a delayed matching-to-sample (DMS) task and a post-scan subsequent recognition memory task of items encountered during DMS task performance. Multiple regression analyses revealed fMRI activity in parahippocampal structures associated with the active maintenance of trial-unique visual information during a brief memory delay. In addition to a role in active maintenance, we found that the subsequent memory for the sample stimuli as measured by the post-scan subsequent recognition memory task correlated with activity in the parahippocampal gyrus during the delay period. The results provide direct evidence that encoding mechanisms are engaged during brief memory delays when novel information is actively maintained. The relationship between active maintenance during the delay period and long-term subsequent memory is consistent with current theoretical models and experimental data that suggest that long-term encoding is enhanced by sustained parahippocampal activity. C1 Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. Boston Univ, Program Neurosci, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Stern, CE (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM chantal@bu.edu OI Hasselmo, Michael/0000-0002-9925-6377 FU NIMH NIH HHS [R01 MH61492]; NINDS NIH HHS [R01 NS41636] NR 58 TC 129 Z9 130 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 8 PY 2004 VL 24 IS 49 BP 11088 EP 11097 DI 10.1523/JNEUROSCI.3807-04.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 878AI UT WOS:000225618300011 PM 15590925 ER PT J AU Reddy, VY Malchano, ZJ Holmvang, G Schmidt, EJ d'Avila, A Houghtaling, C Chan, RC Ruskin, JN AF Reddy, VY Malchano, ZJ Holmvang, G Schmidt, EJ d'Avila, A Houghtaling, C Chan, RC Ruskin, JN TI Integration of cardiac magnetic resonance imaging with three-dimensional electroanatomic mapping to guide left ventricular catheter manipulation - Feasibility in a porcine model of healed myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SINUS RHYTHM; ABLATION; TACHYCARDIAS; HEART AB OBJECTIVES In a series of in vitro and in vivo experiments, we evaluated the feasibility of integrating three-dimensional (3D) magnetic resonance imaging (MRI) and electroanatomic mapping (EAM) data to guide real-time left ventricular (LV) catheter manipulation. BACKGROUND Substrate-based catheter ablation of post-myocardial infarction ventricular tachycardia requires delineation of the scarred myocardium, typically using an EAM system. Cardiac MRI might facilitate this procedure by localizing this myocardial scar. METHODS A custom program was employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic model of the LV was used to determine the optimal alignment/registration strategy. To determine the in vivo accuracy of the registration process, ablation lesions were directed at iatrogenic MRI-visible "targets" (iron oxide injections) within normal porcine LVs (n = 5). Finally, this image integration strategy was assessed in a porcine infarction model (n = 6) by targeting ablation lesions to the scar border. RESULTS The in vitro experiments revealed that registration of the LV alone results in inaccurate alignment due primarily to rotation along the chamber's long axis. Inclusion of the aorta in the registration process rectified this error. In the iron oxide injection experiments, the ablation lesions were 1.8 +/- 0.5 mm from the targets. In the porcine infarct model, the catheter could be reliably navigated to the initial valve annulus, and the ablation lesions were uniformly situated at the scar borders. CONCLUSIONS These data suggest that registration of pre-acquired magnetic resonance images with real-time mapping is sufficiently accurate to guide LV catheter manipulation in a reliable and clinically relevant manner. (C) 2004 by the American College of Cardiology Foundation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. GE Med Syst, Waukesha, WI USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 FU NHLBI NIH HHS [HL68064-02] NR 15 TC 111 Z9 115 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 7 PY 2004 VL 44 IS 11 BP 2202 EP 2213 DI 10.1016/j.jacc.2004.08.063 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 879FT UT WOS:000225702500014 PM 15582319 ER PT J AU Grazette, LP Boecker, W Matsui, T Semigran, M Force, TL Hajjar, RJ Rosenzweig, A AF Grazette, LP Boecker, W Matsui, T Semigran, M Force, TL Hajjar, RJ Rosenzweig, A TI Inhibition of ErbB2 causes mitochondrial dysfunction in cardiornyocytes - Implications for herceptin-induced cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DILATED CARDIOMYOPATHY; MONOCLONAL-ANTIBODY; APOPTOSIS; CARDIOMYOCYTES; SURVIVAL; BCL-X(L); GROWTH; NEUREGULINS; MODULATION; EXPRESSION AB OBJECTIVES We investigated the effects of erbB2 inhibition by anti-erbB2 antibody on cardiomyocyte survival and mitochondrial function. BACKGROUND ErbB2 is an important signal integrator for the epidermal growth factor family of receptor tyrosine kinases. Herceptin, an inhibitory antibody to the erbB2 receptor, is a potent chemotherapeutic but causes cardiac toxicity. METHODS Primary cultures of neonatal rat ventricular myocytes were exposed to anti-erbB2 antibody (Ab) (7.5 mug/ml) for up to 24 h. Cell viability, mitochondrial function, and apoptosis were measured using multiple complementary techniques. RESULTS ErbB2 inhibition was associated with a dramatic increase in expression of the pro-apoptotic Bcl-2 family protein Bcl-xS and decreased levels of anti-apoptotic Bcl-xL. There was a time-dependent increase in mitochondrial translocation and oligomerization of bcl-associated protein (BAX), as indicated by 1,6-bismaleimidohexane crossfinking. The BAX oligomerization was associated with cytochrome c release and caspase activation. These alterations induced mitochondrial dysfunction, a loss of mitochondrial membrane potential (psi) (76.9 +/- 2.4 vs. 51.7 +/- 0.1; p < 0.05; n = 4), a 35% decline in adenosine triphosphate levels (p < 0.05), and a loss of redox capacity (0.72 +/- 0.04 vs. 0.64 +/- 0.02; p < 0.01). Restoration of Bcl-xL levels through transactivating regulatory protein-mediated protein transduction prevented the decline in psi mitochondrial reductase activity and cytosolic adenosine triphosphate. CONCLUSIONS Anti-erbB2 activates the mitochondrial apoptosis pathway through a previously undescribed modulation of Bcl-xL and -xS, causing impairment of mitochondrial function and integrity and disruption of cellular energetics. (C) 2004 by the American College of Cardiology Foundation. C1 Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Tufts New England Med Ctr, Boston, MA USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, 114 16th St,Room 2600, Charlestown, MA 02129 USA. EM arosenzweig@partners.org FU NHLBI NIH HHS [HL-073363, HL-04250, HL-59521, HL-61557, HL-67716]; PHS HHS [50361, 57623] NR 34 TC 119 Z9 122 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC 7 PY 2004 VL 44 IS 11 BP 2231 EP 2238 DI 10.1016/j.jacc.2004.08.066 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 879FT UT WOS:000225702500017 PM 15582322 ER PT J AU Sharp, GC Jiang, SB Shimizu, S Shirato, H AF Sharp, GC Jiang, SB Shimizu, S Shirato, H TI Tracking errors in a prototype real-time tumour tracking system SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID GATED RADIOTHERAPY; FEASIBILITY; RADIOSURGERY; MOVEMENT; THERAPY; MARKER; MOTION AB In motion-compensated radiation therapy, radio-opaque markers can be implanted in or near a tumour and tracked in real-time using fluoroscopic imaging. Tracking these implanted markers gives highly accurate position information, except when tracking fails due to poor or ambiguous imaging conditions. This study investigates methods for automatic detection of tracking errors, and assesses the frequency and impact of tracking errors on treatments using the prototype real-time tumour tracking system. We investigated four indicators for automatic detection of tracking errors. and found that the, distance between corresponding rays was most effective. We also found that tracking errors cause a loss of gating efficiency of between 7.6 and 10.2%. The incidence of treatment beam delivery during tracking errors was estimated at between 0.8% and 1.25%. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. RP Sharp, GC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM gcsharp@partners.org RI Shimizu, Shinichi/G-4477-2010; Shirato, Hiroki/A-7068-2010 OI Shimizu, Shinichi/0000-0003-3143-0479; NR 30 TC 22 Z9 23 U1 0 U2 3 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 DEC 7 PY 2004 VL 49 IS 23 BP 5347 EP 5356 AR PII S0031-9155(04)85063-2 DI 10.1088/0031-9155/49/23/011 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 888WZ UT WOS:000226406200011 PM 15656282 ER PT J AU Wu, HM Sharp, GC Salzberg, B Kaeli, D Shirato, H Jiang, SB AF Wu, HM Sharp, GC Salzberg, B Kaeli, D Shirato, H Jiang, SB TI A finite state model for respiratory motion analysis in image guided radiation therapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID REAL-TIME TUMOR; ORGAN MOTION; RADIOTHERAPY; LUNG; FEASIBILITY AB Effective image guided radiation treatment of a moving tumour requires adequate information on respiratory motion characteristics. For margin expansion, beam tracking and respiratory gating. the rumour motion must be quantified for pretreatment planning and monitored on-line. We propose a finite state model for respiratory motion analysis that captures our natural understanding, of breathing stages. In this model. a regular breathing cycle is represented by three line segments, exhale, end-of-exhale and inhale. while abnormal breathing is represented by an irregular breathing state. In addition. we describe an on-line implementation of this model in one dimension. We found this model can accurately characterize a wide variety of patient breathing patterns. This model was used to describe the respiratory motion for 23 patients with peak-to-peak motion greater than 7 mm. The average root mean square error over all patients was less than I mm and no patient has an error worse than 1.5 mm. Our model provides a convenient toot to quantify respiratory motion characteristics, such as patterns of frequency changes and amplitude changes. and can be applied to internal or external motion. including internal tumour position, abdominal surface, diaphragm. spirometry and other surrogates. C1 Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. RP Wu, HM (reprint author), Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. EM maggiewu@ccs.neu.edu RI Shirato, Hiroki/A-7068-2010 NR 14 TC 60 Z9 62 U1 0 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 DEC 7 PY 2004 VL 49 IS 23 BP 5357 EP 5372 AR PII S0031-9155(04)85065-6 DI 10.1088/0031-9155/49/23/012 PG 16 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 888WZ UT WOS:000226406200012 PM 15656283 ER PT J AU Ming, Y Burel, SA Peterson, LF Kanbe, E Iwasaki, H Boyapati, A Hines, R Akashi, K Zhang, DE AF Ming, Y Burel, SA Peterson, LF Kanbe, E Iwasaki, H Boyapati, A Hines, R Akashi, K Zhang, DE TI Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE t(8;21); truncated protein; hematopoietic malignancy; mouse model; cell cycle ID ACUTE MYELOID-LEUKEMIA; AML1/ETO FUSION TRANSCRIPTS; ACUTE MYELOGENOUS LEUKEMIA; SELF-RENEWAL; REPRESSES TRANSCRIPTION; EMBRYONIC LETHALITY; HEMATOPOIETIC-CELLS; UP-REGULATION; MURINE MODEL; GENE AB Normal blood-cell differentiation is controlled by regulated gene expression and signal transduction. Transcription deregulation due to chromosomal translocation is a common theme in hematopoietic neoplasms. AML1-ETO, which is a fusion protein generated by the 8;21 translocation that is commonly associated with the development of acute myeloid leukemia, fuses the AML1 runx family DNA-binding transcription factor to the ETO corepressor that associates with histone deacetylase complexes. Analyses have demonstrated that AML1-ETO blocks AML1 function and requires additional mutagenic events to promote leukemia. Here, we report that the loss of the molecular events of AML1-ETO C-terminal NCoR/SMRT-interacting domain transforms AML1-ETO into a potent leukemogenic protein. Contrary to full-length AML1-ETO, the truncated form promotes in vitro growth and does not obstruct the cell-cycle machinery. These observations suggest a previously uncharacterized mechanism of tumorigenesis, in which secondary mutation(s) in molecular events disrupting the function of a domain of the oncogene promote the development of malignancy. C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Zhang, DE (reprint author), Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. EM dzhang@scripps.edu NR 51 TC 0 Z9 0 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 7 PY 2004 VL 101 IS 49 BP 17186 EP 17191 DI 10.1073/pnas.0406702101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100038 ER PT J AU Inada, M Wang, YM Byrne, MH Rahman, MU Miyaura, C Lopez-Otin, C Krane, SM AF Inada, M Wang, YM Byrne, MH Rahman, MU Miyaura, C Lopez-Otin, C Krane, SM TI Critical roles for collagenase-3 (Mmp13) in development of growth and in endochondral plate cartilage ossification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE collagen; extracellular matrix; vascularization ID INTERSTITIAL COLLAGENASE; MATRIX METALLOPROTEINASES; HYPERTROPHIC CHONDROCYTES; PARATHYROID-HORMONE; BONE-RESORPTION; I COLLAGEN; X COLLAGEN; TRANSCRIPTION FACTOR; GENE-EXPRESSION; MICE AB Collagenase-3 (MMP13), a member of the matrix metalloproteinase (MMP) family of neutral endopeptidases, is expressed in the skeleton during embryonic development and is highly overexpressed in human carcinomas and in chondrocytes and synovial cells in rheumatoid arthritis and osteoarthritis. To determine the functional roles of Mmp13, we generated Mmp13-null mice that showed profound defects in growth plate cartilage with markedly increased hypertrophic domains as well as delay in endochondral ossification and formation and vascularization of primary ossification centers. Absence of Mmp13 resulted in significant interstitial collagen accumulation due, in part, to the lack of appropriate collagenase-mediated cleavage that normally occurs in growth plates and primary ossification centers. Cartilaginous growth plate abnormalities persisted in adult mice and phenocopied defects observed in human hereditary chondrodysplasias. Our findings demonstrate a unique role of Mmp13 in skeletal development. C1 Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Dept Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, Koganei, Tokyo 1848588, Japan. Univ Oviedo, Inst Univ Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. RP Krane, SM (reprint author), Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Dept Med, Bldg 149,13th St,Room 8301, Boston, MA 02129 USA. EM krane.stephen@mgh.harvard.edu RI miyaura, chisato/D-1864-2013; Lopez-Otin, Carlos/C-6657-2013 OI miyaura, chisato/0000-0002-2548-8191; Lopez-Otin, Carlos/0000-0001-6964-1904 FU NIAMS NIH HHS [P50 AR044855, P50AR44855, R01 AR044815, R01AR44815] NR 46 TC 307 Z9 316 U1 5 U2 15 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 DEC 7 PY 2004 VL 101 IS 49 BP 17192 EP 17197 DI 10.1073/pnas.0407788101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 879SV UT WOS:000225740100039 PM 15563592 ER PT J AU Okamura, K Tanaka, H Yagita, Y Saekl, Y Taguchi, A Hiraoka, Y Zeng, LH Colman, DR Miki, N AF Okamura, K Tanaka, H Yagita, Y Saekl, Y Taguchi, A Hiraoka, Y Zeng, LH Colman, DR Miki, N TI Cadherin activity is required for activity-induced spine remodeling SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; ACTIN-BASED PLASTICITY; CHICK OPTIC TECTUM; DENDRITIC SPINES; CELL-ADHESION; N-CADHERIN; HIPPOCAMPAL-NEURONS; MOUSE HIPPOCAMPUS; SYNAPTIC ACTIVITY; NMDA RECEPTORS AB Neural activity induces the remodeling of pre- and postsynaptic membranes, which maintain their apposition through cell adhesion molecules. Among them, N-cadherin is redistributed, undergoes activity-dependent conformational changes, and is required for synaptic plasticity. Here, we show that depolarization induces the enlargement of the width of spine head, and that cadherin activity is essential for this synaptic rearrangement. Dendritic spines visualized with green fluorescent protein in hippocampal neurons showed an expansion by the activation of AMPA receptor, so that the synaptic apposition zone may be expanded. N-cadherin-venus fusion protein laterally dispersed along the expanding spine head. Overexpression of dominant-negative forms of N-cadherin resulted in the abrogation of the spine expansion. Inhibition of actin polymerization with cytochalasin D abolished the spine expansion. Together, our data suggest that cadherin-based adhesion machinery coupled with the actin-cytoskeleton is critical for the remodeling of synaptic apposition zone. C1 Osaka Univ, Sch Med, Dept Pharmacol, Suita, Osaka 5650871, Japan. Osaka Univ, Sch Med, Dept Internal Med, Suita, Osaka 5650871, Japan. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. Massachusetts Gen Hosp, Lab Neuro Oncol, Boston, MA 02114 USA. Natl Cardiovasc Ctr, Suita, Osaka 5658565, Japan. Natl Inst Informat & Commun Technol, Kansai Adv Res Ctr, Kobe, Hyogo 6512492, Japan. RP Tanaka, H (reprint author), Osaka Univ, Sch Med, Dept Pharmacol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM htanaka@pharma1.med.osaka-u.ac.jp RI Hiraoka, Yasushi/B-5111-2009; Yagita, Yoshiki/S-6954-2016 OI Hiraoka, Yasushi/0000-0001-9407-8228; FU NINDS NIH HHS [NS20147, R01 NS020147] NR 43 TC 93 Z9 96 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 6 PY 2004 VL 167 IS 5 BP 961 EP 972 DI 10.1083/jcb.200406030 PG 12 WC Cell Biology SC Cell Biology GA 879FD UT WOS:000225700900016 PM 15569714 ER PT J AU Chen, RW Zhang, YQ Rose, ME Graham, SH AF Chen, RW Zhang, YQ Rose, ME Graham, SH TI Cyclooxygenase-2 activity contributes to neuronal expression of cyclin D1 after anoxia/ischemia in vitro and in vivo SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ischemia; cyclooxygenase; cell cycle; cyclin d1 ID AMYOTROPHIC-LATERAL-SCLEROSIS; CELL-CYCLE; ALZHEIMERS-DISEASE; DEPENDENT KINASES; ANTIINFLAMMATORY DRUGS; CEREBRAL-ISCHEMIA; DEATH; APOPTOSIS; BRAIN; INHIBITORS AB Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of neuronal cell death in ischemia and other diseases, but the mechanism by which COX-2 exacerbates cell death is unknown. COX-2 activity, is known to induce expression of cyclin D I in neoplastic cells, and cyclin D1 expression can induce cell death in postmitotic neurons. In the present study, the role of COX-2 and cyclin D1 in neuronal cell death induced by anoxia and ischemia was examined. Treatment with the COX-2 specific inhibitor (NS 398 25 muM) and cyclin D1 inhibitor (flavopiridol 1 muM) increased neuronal survival and inhibited DNA fragmentation after anoxia. NS-398 suppressed anoxia-induced expression of cyclin D1. Flavopiridol inhibited the anoxia-induced increased expression of cyclin D1, but had no effect on COX-2 expression. Treatment with the selective COX-2 inhibitor, SC58125, had no affect on COX-2 expression but partially suppressed cyclin D1 expression in the cortex following middle cerebral artery occlusion in vivo. These results show that COX-2 activity is required for cyclin D I expression after ischemia in vivo and anoxia in vitro. These data provide support for the hypothesis that cyclin D1 expression is an important mechanism by which COX-2 activity exacerbates ischemic neuronal death. (C) 2004 Elsevier B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Res Serv 151, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Res Serv 151, Univ Dr C, Pittsburgh, PA 15240 USA. EM sgra@pitt.edu NR 42 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 6 PY 2004 VL 132 IS 1 BP 31 EP 37 DI 10.1016/j.molbrainres.2004.08.020 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 876LX UT WOS:000225499500004 ER PT J AU Banta, S Yokoyama, T Berthiaume, F Yarmush, ML AF Banta, S Yokoyama, T Berthiaume, F Yarmush, ML TI Quantitative effects of thermal injury and insulin on the metabolism of the skeletal muscle using the perfused rat hindquarter preparation SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE skeletal muscle metabolism; hindquarter perfusion; proteolysis; muscle wasting; metabolic flux analysis ID AMINO-ACID-METABOLISM; GLUTAMINE-SYNTHETASE EXPRESSION; SEVERELY BURNED PATIENTS; PROTEIN-SYNTHESIS; GLUCOSE-UPTAKE; HYPERCATABOLIC PATIENTS; SYSTEMIC HYPERINSULINEMIA; FATTY-ACIDS; WHOLE-BODY; LEUCINE AB Injury from a severe burn or trauma can propel the body into a hypermetabolic state that can lead to the significant erosion of lean muscle mass. Investigations describing this process have been somewhat limited due to the lack of adequate experimental models. Here we report the use of a perfused rat hindquarter preparation to study the consequences of a moderate burn injury (approximate to 20% total body surface area), with or without the addition of exogenous insulin (112.5 mU/mL), on the fluxes of major metabolites across the isolated skeletal muscle. The metabolic flux data was further analyzed using metabolic flux analysis (MFA), which allows for the estimation of the impact of these conditions on the intracellular muscle metabolism. Results indicate that this model is able to capture the increased rate of proteolysis, glutamine formation, and the negative nitrogen balance associated with the burn-induced hypermetabolic state. The inclusion of exogenous insulin resulted in significant changes in several fluxes, including an increase in the metabolism of glucose and the flux through the pentose phosphate pathway, as well as a reduction in the metabolism of glutamine, alanine, and leucine. However, insulin administration did not affect the nitrogen balance or the rate of proteolysis in the muscle, as has been suggested using other techniques. The use of the perfused hindquarter model coupled with MFA is a physiologically relevant and experimentally flexible platform for the exploration of skeletal muscle metabolism under catabolic conditions, and it will be useful in quantifying the specific metabolic consequences of other therapeutic advances. (C) 2004 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [R01 DK 59766] NR 74 TC 7 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD DEC 5 PY 2004 VL 88 IS 5 BP 613 EP 629 DI 10.1002/bit.20258 PG 17 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 874LG UT WOS:000225351300008 PM 15470703 ER PT J AU Grundner, C Pancera, M Kang, JM Koch, M Sodroski, J Wyatt, R AF Grundner, C Pancera, M Kang, JM Koch, M Sodroski, J Wyatt, R TI Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins SO VIROLOGY LA English DT Article DE HIV-1; envelope glycoproteins; immunogenicity ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL-EPITOPE; MHC CLASS-II; NEUTRALIZING ANTIBODIES; 3-DIMENSIONAL STRUCTURE; VARIABLE REGIONS; RECEPTOR-BINDING; PEPTIDES; RESPONSES; PROTEIN AB Efficient immune responses to HIV-1 gene products are essential elements to the development and design of an effective vaccine. Ideally, both humoral and cellular responses will be optimally elicited. It is therefore important to elucidate any factors that might limit the immumogenicity of HIV-1 proteins that are likely to be included in an effective vaccine. Since the HIV-1 exterior envelope glycoprotein gp 120 is a major target for neutralizing antibodies, it is a virtual certainty that this gene product will be a component of any vaccine that seeks to elicit neutralizing antibody responses from the host humoral immune system. We report here the testing of several HIV-1 gp 120 variants derived from a primary isolate that appears deficient in eliciting immune responses at both the level of CD4+ help and consequently in the generation of high-affinity IgG antibody responses in small animals. Factors limiting an effective immune response include (a) envelope glycoprotein strain variation decreasing functional T-cell help, (b) alteration of the glycosylation patterns of gp 120 by expression in different cell types, and (c) the native structure of gp 120 itself, which may limit the elicitation of effective T-cell help during natural infection or during parenteral immunization in adjuvant. Such limiting factors and others should be considered in the design and testing of gpl20-based immumogens in small animals and possibly in primates as well. C1 NIH, Struct Virol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIH, Struct Virol Sect, Vaccine Res Ctr, 40 Convent Dr,Bldg 40, Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU NIAID NIH HHS [5 R21 AI-44328-02, 1 R21 AI-44328-02] NR 56 TC 38 Z9 39 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 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2004 VL 330 IS 1 BP 233 EP 248 DI 10.1016/j.virol.2004.08.037 PG 16 WC Virology SC Virology GA 872GL UT WOS:000225195600022 PM 15527849 ER PT J AU Mollica, RF Cardozo, BL Osofsky, HJ Raphael, B Ager, A Salama, P AF Mollica, RF Cardozo, BL Osofsky, HJ Raphael, B Ager, A Salama, P TI Mental health in complex emergencies SO LANCET LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; EYE-MOVEMENT DESENSITIZATION; NATIONAL COMORBIDITY SURVEY; PUBLIC-HEALTH; POLITICAL VIOLENCE; FUNCTIONAL HEALTH; BEHAVIOR PROBLEMS; BOSNIAN REFUGEES; BORDER CAMPS; PRIMARY-CARE AB Mental health is becoming a central issue for public health complex emergencies. In this review we present a culturally valid mental health action plan based on scientific evidence that is capable of addressing the mental health effects of complex emergencies. A mental health system of primary care providers, traditional healers, and relief workers, if properly trained and supported, can provide cost-effective, good mental health care. This plan emphasises the need for standardised approaches to the assessment, monitoring, and outcome of all related activities. Crucial to the improvement of outcomes during crises and the availability to future emergencies of lessons learned from earlier crises is the regular dissemination of the results achieved with the action plan. A research agenda is included that should, in time, fill knowledge gaps and reduce the negative mental health effects of complex emergencies. C1 Massachusetts Gen Hosp, Harvard Program Refugee Trauma, Cambridge, MA USA. Ctr Dis Control & Prevent, Int Emergency & Reguee Hlth Branch, Atlanta, GA USA. Louisiana State Univ, Hlth Sci Ctr, Baton Rouge, LA 70803 USA. New S Wales Hlth Dept, Ctr Mental Hlth, Sydney, NSW, Australia. Ctr Int Hlth Studies, Edinburgh, Midlothian, Scotland. UNICEF, Kabul, Afghanistan. RP Mollica, RF (reprint author), Harvard Program Refugee Trauma, 22 Putnam Ave 2nd Floor, Cambridge, MA 02139 USA. EM rmollica@partners.org NR 145 TC 109 Z9 112 U1 4 U2 17 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 4 PY 2004 VL 364 IS 9450 BP 2058 EP 2067 DI 10.1016/S0140-6736(04)17519-3 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 876KM UT WOS:000225495700030 PM 15582064 ER PT J AU Milush, JA Kosub, D Marthas, M Schmidt, K Scott, F Wozniakowski, A Brown, C Westmoreland, S Sodora, DL AF Milush, JA Kosub, D Marthas, M Schmidt, K Scott, F Wozniakowski, A Brown, C Westmoreland, S Sodora, DL TI Rapid dissemination of SIV following oral inoculation SO AIDS LA English DT Article DE SIV; HIV; oral transmission; macaque; acute SIV infection ID SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; NEWBORN RHESUS MACAQUES; MONOCLONAL-ANTIBODIES; PASSIVE-IMMUNIZATION; INTRAVAGINAL INOCULATION; SEXUAL TRANSMISSION; NEONATAL MACAQUES; NONHUMAN-PRIMATES; VIRAL REPLICATION AB Objective: To assess the earliest events regarding transmission and dissemination of SIV following nontraumatic oral inoculation in macaques. Design: Juvenile and neonate rhesus macaques were orally inoculated with SIVmac251 and necropsied at 1, 2, 4, 7, or 14 days post-inoculation. Sites of transmission and the extent of viral spread were assessed by using molecular techniques and in situ hybridization to identify SIV nucleic acid in lymphoid and nonlymphoid tissues. Results: This study demonstrates that 1 day post-exposure, SIV nucleic acid was detected in the alimentary canal only in tissues proximal to the stomach, including the oral and esophageal mucosa as well as the tonsils. Following infection, virus was observed to spread rapidly to regional and peripheral lymph nodes by 1 and 2 days post-inoculation (dpi). Hundreds of copies of SIV-DNA were detected 4 dpi, increasing to > 10 000 copies/1 x 10(6) cells by 7 dpi. Identification of SIV positive T cells and macrophages implicates these cell types in viral spread, although dissemination of free virus is also likely. Conclusions: Here the oral and esophageal mucosa, as well as tonsils, are demonstrated to be potential sites for viral infection upon nontraumatic oral exposure to SIV in macaques. The rapid dissemination following oral transmission observed in this study is reflective of SIV transmission across other mucosal surfaces. The rapidity with which SIV, and probably HIV, spreads throughout the lymphatics indicates a major obstacle for a vaccine amnestic immune response to eliminate infected cells prior to dissemination. (C) 2004 Lippincott Williams Wilkins. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Calif Davis, California Natl Primate Res Ctr, Davis, CA 95616 USA. NIAID, Mol Microbiol Lab, NIH, Rockville, MD USA. Massachusetts Gen Hosp, Charlestown, MA USA. RP Sodora, DL (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM DonaId.Sodora@UTSouthwestern.edu FU NCRR NIH HHS [RR 00169, RR 000150, RR 00168, RR 017740]; NIAID NIH HHS [5T32 AI 005284, 5T32 AI 07520, AI 35522]; NIDCR NIH HHS [DE 12926] NR 50 TC 47 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD DEC 3 PY 2004 VL 18 IS 18 BP 2371 EP 2380 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 884BR UT WOS:000226060100004 PM 15622313 ER PT J AU Li, Q Cherayil, BJ AF Li, Q Cherayil, BJ TI Toll-like receptor 4 mutation impairs the macrophage TNF alpha response to peptidoglycan SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE macrophage; inflammation; lipopolysaccharide; peptidoglycan; TNF alpha; toll-like receptors ID ENTERICA SEROVAR TYPHIMURIUM; NF-KAPPA-B; SIGNALING PATHWAY; SALMONELLA-TYPHIMURIUM; HOST-DEFENSE; MICE; TOLERANCE; INFECTION; TLR4; SUSCEPTIBILITY AB Macrophages produce TNFalpha when infected by bacteria, a response that follows recognition of microbial components by members of the Toll-like receptor (TLR) family. Cells that lack functional TLR4 are known to have markedly diminished responses to Gram-negative lipopolysaccharide. We demonstrate in the present work that peritoneal macrophages derived from strains of mice that carry a spontaneous, inactivating mutation in TLR4 also have impaired production of TNFalpha in response to peptidoglycan, a ligand for TLR2. This impairment is at a step of biosynthesis subsequent to the generation of mRNA. TLR4-activated signals act at this step to enhance peptidoglycan-induced TNFa production in wild-type mice. Based on these observations, we conclude that macrophages from wild-type mice are primed by chronically acting TLR4 signals, probably resulting from exposure to environmental lipopolysaccharide. These signals are required for optimal production of TNFalpha in response to TLR2 stimulation, and are absent in macrophages from TLR4 mutant animals. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Gastroenterol Unit, Boston, MA USA. RP Cherayil, BJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Gastroenterol Unit, Boston, MA USA. EM cherayil@helix.mgh.harvard.edu FU NIAID NIH HHS [R01-AI48815] NR 31 TC 3 Z9 4 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 DEC 3 PY 2004 VL 325 IS 1 BP 91 EP 96 DI 10.1016/j.bbrc.2004.10.008 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871YU UT WOS:000225173400014 PM 15522205 ER PT J AU Klucken, J Shin, Y Hyman, BT McLean, PJ AF Klucken, J Shin, Y Hyman, BT McLean, PJ TI A single amino acid substitution differentiates Hsp70-dependent effects on alpha-synuclein degradation and toxicity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE neurodegeneration; Parkinson's disease; dementia with Lewy bodies; chaperone; protein aggregation ID MOLECULAR CHAPERONES; HSP70; AGGREGATION; PROTEASOME; PROTEIN; UBIQUITINATION; SUPPRESSION; HSC70; CHIP AB alpha-Synuclein aggregation and toxicity play a major role in Parkinson's disease and dementia with Lewy bodies. Hsp70 is a multipurpose stress response chaperone protein that mediates both refolding and degradation of misfolded proteins. We have shown that Hsp70 is able to block both alpha-synuclein toxicity and aggregation. Here we introduce a mutation into the ATPase domain of Hsp70 (K71S) and demonstrate that this abolishes Hsp70 refolding activity. Nonetheless, Hsp70K71S continues to mediate alpha-synuclein degradation and blocks aggregate formation. In contrast to wild type Hsp70, the ATPase domain mutant mediates alpha-synuclein degradation through a non-proteasome inhibitor sensitive pathway. Although Hsp70K71S can diminish levels of alpha-synuclein to an even greater extent than Hsp70, HSP70K71S does not protect against alpha-synuclein toxicity. The Hsp70K71S mutant appears to dissociate the formation of aggregates, which it blocks, and toxicity, which it does not block. These data suggest that the ability of Hsp70 to prevent toxicity is distinct from degradation of alpha-synuclein and is dependent on its ATPase domain. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimer Dis Res Unit, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP McLean, PJ (reprint author), Massachusetts Gen Hosp, Alzheimer Dis Res Unit, MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM pmclean@partners.org FU NIA NIH HHS [AG18440]; NINDS NIH HHS [NS38372] NR 16 TC 27 Z9 28 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 3 PY 2004 VL 325 IS 1 BP 367 EP 373 DI 10.1016/j.bbrc.2004.10.037 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871YU UT WOS:000225173400050 PM 15522241 ER PT J AU Khurts, S Masutomi, K Delgermaa, L Arai, K Oishi, N Mizuno, H Hayashi, N Hahn, WC Murakami, S AF Khurts, S Masutomi, K Delgermaa, L Arai, K Oishi, N Mizuno, H Hayashi, N Hahn, WC Murakami, S TI Nucleolin interacts with telomerase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C VIRUS NS5B; CATALYTIC SUBUNIT; RNA COMPONENT; HUMAN-CELLS; IN-VITRO; REVERSE-TRANSCRIPTASE; ENZYME-ACTIVITY; PROTEIN; LOCALIZATION; DOMAIN AB Telomerase is a specialized reverse transcriptase composed of core RNA and protein subunits which plays essential roles in maintaining telomeres in actively dividing cells. Recent work indicates that telomerase shuttles between subcellular compartments during assembly and in response to specific stimuli. In particular, telomerase colocalizes with nucleoli in normal human fibroblasts. Here, we show that nucleolin, a major nucleolar phosphoprotein, interacts with telomerase and alters its subcellular localization. Nucleolin binds the human telomerase reverse transcriptase subunit ( hTERT) through interactions with its RNA binding domain 4 and carboxyl-terminal RGG domain, and this binding also involves the telomerase RNA subunit hTERC. The protein-protein interaction between nucleolin and hTERT is critical for the nucleolar localization of hTERT. These findings indicate that interaction of hTERT and nucleolin participates in the dynamic intracellular localization of telomerase complex. C1 Kanazawa Univ, Canc Res Inst, Dept Mol Biol, Kanazawa, Ishikawa 9200934, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Murakami, S (reprint author), Kanazawa Univ, Canc Res Inst, Dept Mol Biol, Takara Machi 13-1, Kanazawa, Ishikawa 9200934, Japan. EM semuraka@kenroku.kanazawa-u.ac.jp RI Mizuno, Hideki/E-9133-2011 FU NCI NIH HHS [K01 CA94223] NR 33 TC 71 Z9 79 U1 1 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 DEC 3 PY 2004 VL 279 IS 49 BP 51508 EP 51515 DI 10.1074/jbc.M407643200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 874MZ UT WOS:000225355800104 PM 15371412 ER PT J AU Fotin, A Cheng, YF Sliz, P Grigorieff, N Harrison, SC Kirchhausen, T Walz, T AF Fotin, A Cheng, YF Sliz, P Grigorieff, N Harrison, SC Kirchhausen, T Walz, T TI Molecular model for a complete clathrin lattice from electron cryomicroscopy SO NATURE LA English DT Article ID LIGHT-CHAINS; COATED VESICLES; 3-DIMENSIONAL STRUCTURE; TRIMERS; LOCATION; TRIMERIZATION; STABILIZATION; ORGANIZATION; SUPERHELIX; MICROSCOPY AB Clathrin-coated vesicles are important vehicles of membrane traffic in cells. We report the structure of a clathrin lattice at subnanometre resolution, obtained from electron cryomicroscopy of coats assembled in vitro. We trace most of the 1,675-residue clathrin heavy chain by fitting known crystal structures of two segments, and homology models of the rest, into the electron microscopy density map. We also define the position of the central helical segment of the light chain. A helical tripod, the carboxyterminal parts of three heavy chains, projects inward from the vertex of each three-legged clathrin triskelion, linking that vertex to 'ankles' of triskelions centred two vertices away. Analysis of coats with distinct diameters shows an invariant pattern of contacts in the neighbourhood of each vertex, with more variable interactions along the extended parts of the triskelion 'legs'. These invariant local interactions appear to stabilize the lattice, allowing assembly and uncoating to be controlled by events at a few specific sites. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Biophys Grad Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem, Waltham, MA 02454 USA. Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA. RP Harrison, SC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave, Boston, MA 02115 USA. EM Harrison@crystal.harvard.edu OI Sliz, Piotr/0000-0002-6522-0835 NR 40 TC 284 Z9 287 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 2 PY 2004 VL 432 IS 7017 BP 573 EP 579 DI 10.1038/nature03079 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 875PL UT WOS:000225433200035 PM 15502812 ER PT J AU Fotin, A Cheng, YF Grigorieff, N Walz, T Harrison, SC Kirchhausen, T AF Fotin, A Cheng, YF Grigorieff, N Walz, T Harrison, SC Kirchhausen, T TI Structure of an auxilin-bound clathrin coat and its implications for the mechanism of uncoating SO NATURE LA English DT Article ID IN-VIVO; DISSOCIATION; VESICLES; HSC70; IDENTIFICATION; COMPLEX; ATPASE AB Clathrin-coated pits invaginate from specific membrane compartments and pinch off as coated vesicles. These vesicles then uncoat rapidly once released. The Hsc70 molecular chaperone effects the uncoating reaction, and is guided to appropriate locations on clathrin lattices by the J-domain-containing co-chaperone molecule auxilin(1-4). This raises the question of how a local event such as ATP hydrolysis by Hsc70 can catalyse a global disassembly. Here, we have used electron cryomicroscopy to determine 12-Angstrom-resolution structures of in-vitro-assembled clathrin coats in association with a carboxy-terminal fragment of auxilin that contains both the clathrin-binding region and the J domain. We have located the auxilin fragment by computing differences between these structures and those lacking auxilin (described in an accompanying paper(5)). Auxilin binds within the clathrin lattice near contacts between an inward-projecting C-terminal helical tripod and the crossing of two 'ankle' segments; it also contacts the terminal domain of yet another clathrin 'leg'. It therefore recruits Hsc70 to the neighbourhood of a set of critical interactions. Auxilin binding produces a local change in heavy-chain contacts, creating a detectable global distortion of the clathrin coat. We propose a mechanism by which local destabilization of the lattice promotes general uncoating. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Biophys Grad Program, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Howard Hughes Med Inst, Waltham, MA 02454 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biochem, Waltham, MA 02454 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM Kirchhausen@crystal.harvard.edu NR 18 TC 75 Z9 78 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 2 PY 2004 VL 432 IS 7017 BP 649 EP 653 DI 10.1038/nature03078 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 875PL UT WOS:000225433200052 PM 15502813 ER PT J AU Musher, DM Musher, BL AF Musher, DM Musher, BL TI Medical progress - Contagious acute gastrointestinal infections SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID DAY-CARE-CENTERS; HEMOLYTIC-UREMIC-SYNDROME; ASTROVIRUS-ASSOCIATED GASTROENTERITIS; CAMPYLOBACTER-JEJUNI INFECTION; POLYMERASE CHAIN-REACTION; ESCHERICHIA-COLI 0157-H7; ROUND-STRUCTURED VIRUS; NORWALK-LIKE VIRUS; TYPHOID-FEVER; UNITED-STATES C1 Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Musher, DM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. EM daniel.musher@med.va.gov NR 132 TC 83 Z9 87 U1 1 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 DEC 2 PY 2004 VL 351 IS 23 BP 2417 EP 2427 DI 10.1056/NEJMra041837 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 875OC UT WOS:000225429000011 PM 15575058 ER PT J AU Janssen, WJ Dhaliwal, G Collard, HR Saint, S AF Janssen, WJ Dhaliwal, G Collard, HR Saint, S TI Clinical problem-solving - Why "why'' matters SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEMOLYTIC-ANEMIA; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE DEFICIENCY; INDUCED METHEMOGLOBINEMIA C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Ann Arbor Vet Affairs Med Ctr, Patient Safety Enhancement Program, Ann Arbor Vet Affairs Hlth Serv Res & Dev Ctr Exc, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. RP Janssen, WJ (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Pulm Sci & Crit Care Med, 4200 E 9th Ave,Box C-272, Denver, CO 80262 USA. EM janssen@uchsc.edu FU AHRQ HHS [P20-HS11540] NR 15 TC 11 Z9 12 U1 0 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 DEC 2 PY 2004 VL 351 IS 23 BP 2429 EP 2434 DI 10.1056/NEJMcps040669 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 875OC UT WOS:000225429000014 PM 15575060 ER PT J AU Romanova, LY Willers, H Blagosklonny, MV Powell, SN AF Romanova, LY Willers, H Blagosklonny, MV Powell, SN TI The interaction of p53 with replication protein A mediates suppression of homologous recombination SO ONCOGENE LA English DT Article DE p53; RPA; homologous recombination; replication ID WILD-TYPE P53; STRAND BREAK REPAIR; DNA-BINDING DOMAIN; HUMAN RAD51; MUTANT P53; CELL-CYCLE; 3'-TO-5' EXONUCLEASE; HOLLIDAY JUNCTIONS; MAMMALIAN-CELLS; RPA AB The tumor suppressor protein p53 is emerging as a central regulator of homologous recombination (HR) processes and DNA replication. P53 may downregulate HR through multiple mechanisms including the reported associations with the Rad51 and Rad54 recombinases, and the BLM and WRN helicases. Here, we investigated whether the interaction of p53 with human replication protein A (RPA) is necessary for the regulation of HR. By employing a plasmid-based HR assay in p53-null H1299 lung carcinoma cells, we, studied the HR-suppressing properties of a panel of p53 mutants, which varied in their ability to interact with RPA. Both wild-type p53 and a transactivation-deficient p53 mutant (L22Q/W23S) suppressed HR and prevented RPA binding to ssDNA in vitro and in vivo. Conversely, p53 mutations that specifically disrupt the RPA-binding domain, while not compromising p53 transactivation function (D48H/D49H and W53S/F54S), did not affect HR. Suppression of HR was also not seen with missense mutations in the p53 core domain (His175 and His273), which retained the ability to interact with RPA, suggesting that the disruption of additional binding interactions of p53, for example, with Rad51 or recombination intermediates, also impacts on HR. We hypothesize that sequestration of RPA by p53 at the sites of recombination is one means by which p53 can inhibit HR processes. Our data support and extend the previously formulated 'dual model' of p53's role as guardian of the genome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Celllular Radiat Biol, Charlestown, MA 02129 USA. New York Med Coll, Brander Canc Res Inst, Hawthorne, NY 10532 USA. RP Powell, SN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Celllular Radiat Biol, Charlestown, MA 02129 USA. EM snpowell@partners.org FU NCI NIH HHS [CA58985] NR 73 TC 50 Z9 52 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 2 PY 2004 VL 23 IS 56 BP 9025 EP 9033 DI 10.1038/sj.onc.1207982 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 876JN UT WOS:000225492800003 PM 15489903 ER PT J AU Sinenko, SA Mathey-Prevot, B AF Sinenko, SA Mathey-Prevot, B TI Increased expression of Drosophila tetraspanin, Tsp68C, suppresses the abnormal proliferation of ytr-deficient and Ras/Raf-activated hemocytes SO ONCOGENE LA English DT Article DE tetraspanin; Tsp68C; yantar; Raf; hemocyte; Drosophila ID DENDRITIC CELLS; EGF RECEPTOR; SUPERFAMILY; PROTEINS; ORGANIZERS; INTEGRINS; COMPLEXES; MIGRATION; RESPONSES; PATHWAY AB Tetraspanins are evolutionary conserved transmembrane proteins thought to facilitate cell proliferation, movement or fusion by acting as organizers of different signaling events. Despite their prevalence and conservation, their specific role and functions remain largely elusive, as their redundancy in various. organisms has hindered loss of function studies. Here, we take a gain of function approach to study Drosophila tetraspanin Tsp68C and its effect on larval hemocytes. We recently characterized a lethal mutation in ytr, a conserved gene that encodes a nuclear arginine-rich protein of unknown function, which is accompanied by abnormal differentiation and proliferation of the larval hematopoietic tissue in flies. A hemolectin (hml)-Gal4 construct carried by hml-Gal4 transgenic flies was sufficient by itself to abrogate the hematopoietic defects in ytr mutant larvae. This rescue correlated with the overexpression of tsp68C, a tetraspanin gene nested in the hml promoter. The suppression of abnormal proliferation by the hml-Gal4 construct was not restricted to ytr-deficient hemocytes, but was also observed in hemocytes expressing the oncogenic forms of Raf or Ras proteins. However, it had no effect on overproliferation mediated by a constitutively active form of Jak. New hml-Gal4 lines, in which the tsp68C gene was silenced or deleted from the promoter, no longer rescued the hematopoietic defect in ytr mutants nor suppressed the activated Raf-induced overproliferation. Therefore, change in tetraspanin Tsp68C expression has a strong suppressor effect on abnormal proliferation and differentiation of hemocytes in the context of specific lesions, such as overactivation of the Ras/Raf/MAPK pathway. C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Sinenko, SA (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, 621 Charles E Young Dr S,Life Sci Bldg 2204, Los Angeles, CA 90024 USA. EM sinenko@mcdb.ucla.edu RI Sinenko, Sergey/C-3703-2016 FU NHLBI NIH HHS [R01 HL62434] NR 32 TC 51 Z9 51 U1 4 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 2 PY 2004 VL 23 IS 56 BP 9120 EP 9128 DI 10.1038/sj.onc.1208156 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 876JN UT WOS:000225492800013 PM 15480416 ER PT J AU Kumar, A Clark, S Boudreaux, ED Camargo, CA AF Kumar, A Clark, S Boudreaux, ED Camargo, CA TI A multicenter study of depression among emergency department patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE depression; screening; emergency department; risk factors ID NATIONAL-COMORBIDITY-SURVEY; PRIMARY-CARE; EPIDEMIOLOGY; PREVALENCE; SYMPTOMS; DISEASE; ANXIETY; METAANALYSIS; RECOGNITION; DISORDERS AB Objectives: The authors sought to determine the 12-month prevalence of depression among emergency department (ED) patients using a single-question screen. Methods: This cross-sectional study was conducted in four Boston-area EDs. For two 24-hour periods, consecutive patients aged 18 years or older were interviewed, excluding those who were severely ill, potential victims of sexual assault, or emotionally disturbed. During the interview, patients were asked "Have you had any of the following problems during the past 12 months?" Patients answered "yes" or "no" to a list of health problems that included depression. In a validation study, the authors found that this simple approach correlated well with results from the validated Center for Epidemiologic Studies Depression Scale. Results: Of 752 eligible patients, 539 (72%) were interviewed. Of these patients, 30% (95% confidence interval = 26% to 34%) reported depression within the past 12 months. Compared with their nondepressed counterparts, depressed patients were more likely middle-aged, female, and of lower socioeconomic status. Depressed patients were more likely to be smokers and to report a diagnosis of asthma or arthritis/ rheumatism. In a multivariate analysis, factors that were independently associated with depression were lower level of education, smoking, and self-reported anxiety, chronic fatigue, and back problems. Conclusions: A 30% 12-month prevalence of depression among ED patients was found. Depressed patients had a distinct sociodemographic and health profile. In the future, awareness of risk factors for depression in the ED setting and use of simple screening instruments could aid in the recognition of depression, with subsequent referral to mental health services. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. Univ Med & Dent New Jersey, Cooper Hosp, Camden, NJ 08103 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. EM ccamargo@partners.org OI Boudreaux, Edwin/0000-0002-3223-6371 NR 43 TC 28 Z9 30 U1 1 U2 4 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 DEC PY 2004 VL 11 IS 12 BP 1284 EP 1289 DI 10.1197/j.aem.2004.08.053 PG 6 WC Emergency Medicine SC Emergency Medicine GA 876XE UT WOS:000225531300007 PM 15576518 ER PT J AU Yerevanian, BI Koek, RJ Feusner, JD Hwang, S Mintz, J AF Yerevanian, BI Koek, RJ Feusner, JD Hwang, S Mintz, J TI Antidepressants and suicidal behaviour in unipolar depression SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE depressive disorder; dysthymic disorder; suicide; suicide, attempted; antidepressants; antidepressive agents, tricyclic; serotonin reuptake inhibitors ID AFFECTIVE-DISORDERS; PREVENTION; SWEDEN; RISK; FLUOXETINE; PAROXETINE; MORTALITY; EFFICACY; PLACEBO; LITHIUM AB Objective: To compare the rates of suicidal behaviour during vs. after discontinuation of treatment with antidepressants, and to determine the comparative rates of suicidal behaviour for patients maintained on tricyclic (TCA) vs. selective serotonin reuptake inhibitor (SSRI) antidepressants. Method: Charts were reviewed for 521 patients with major depressive disorder and/or dysthymic disorder. Periods of active treatment or discontinuation with SSRIs or TCAs were determined. Rates of completed suicide, suicide attempts, and hospitalization for suicidality were analyzed. Results: There was greater than a five-fold increase in risk for suicidal behaviour after discontinuation of antidepressant treatment (P < 0.0001). The rates of suicidal behavior during treatment with SSRIs or TCAs were similar. Conclusion: Suicidal behaviour in unipolar depressed patients treated with antidepressants increases substantially after medication discontinuation. This effect occurred in both patients who were maintained on SSRIs and TCAs. The findings support a possible protective effect on suicidal behaviour for both SSRIs and TCAs. C1 LA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Biostat Consultat Unit, Los Angeles, CA 90073 USA. RP Yerevanian, BI (reprint author), 16111 Plummer St 116A, North Hills, CA 91343 USA. EM byerevan@ucla.edu RI Feusner, Jamie/K-2312-2012 OI Feusner, Jamie/0000-0002-0391-345X NR 33 TC 37 Z9 37 U1 1 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 2004 VL 110 IS 6 BP 452 EP 458 DI 10.1111/j.1600-0447.2004.00437.x PG 7 WC Psychiatry SC Psychiatry GA 867TL UT WOS:000224865200008 PM 15521830 ER PT J AU Farabaugh, AH Mischoulon, D Fava, M Green, C Guyker, W Alpert, J AF Farabaugh, AH Mischoulon, D Fava, M Green, C Guyker, W Alpert, J TI The potential relationship between levels of perceived stress and subtypes of major depressive disorder (MDD) SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE perceived stress; subtypes of depression; major depression ID LIFE EVENTS; ATYPICAL DEPRESSION; GENETIC LIABILITY; ANGER ATTACKS; SYMPTOMS; WOMEN; VULNERABILITY; OUTPATIENTS; PREDICTION; EPISODES AB Objective: We wanted to explore whether major depressive disorder (MDD) subtypes (melancholic depression, atypical depression, double depression, and MDD with anger attacks) were related to levels of perceived stress, as measured by the Perceived Stress Scale (PSS). Method: Our sample [n = 298; female = 163 (55%); mean age 40.1 +/- 10.5 years] consisted of out-patients with MDD. The Structured Clinical Interview for DSM-III-R, the 17-item Hamilton Rating Scale for Depression, the Anger Attack Questionnaire, and the PSS were administered prior to initiating treatment. Results: Depressed women had significantly higher levels of perceived stress (P = 0.02) than depressed men. Greater severity of depression at baseline was significantly related to higher levels of perceived stress (P < 0.0001). After adjusting for age, gender, and severity of depression at baseline, higher levels of perceived stress were significantly related to the presence of anger attacks (P < 0.0001; t = -4.103) as well as to atypical depression (P = 0.0013; t = 3.26). Conclusion: Out-patients with MDD who are more irritable and/or present with atypical features have higher levels of perceived stress, indicating a potential reactive component to their depression. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Farabaugh, AH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,MA WAC 812, Boston, MA 02114 USA. EM afarabaugh@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 33 TC 24 Z9 24 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 2004 VL 110 IS 6 BP 465 EP 470 DI 10.1111/j.1600-0447.2004.00377.x PG 6 WC Psychiatry SC Psychiatry GA 867TL UT WOS:000224865200010 PM 15521832 ER PT J AU Wiese, TH Rogalla, P Taupitz, M Wagner, S Schnorr, J Mews, J Enzweiler, CNH Hermann, KGA Hamm, B Lembcke, A AF Wiese, TH Rogalla, P Taupitz, M Wagner, S Schnorr, J Mews, J Enzweiler, CNH Hermann, KGA Hamm, B Lembcke, A TI Assessment of left ventricular volumes and function: Intraindividual comparison of multi-slice spiral CT and electron beam CT in an animal model SO ACTA RADIOLOGICA LA English DT Article DE electron beam CT; image quality; left ventricle; multi-slice spiral CT; volume measurements ID CORONARY-ARTERY STENOSES; MULTIDETECTOR ROW CT; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; TEMPORAL RESOLUTION; MYOCARDIAL-FUNCTION; CARDIAC-FUNCTION; HELICAL CT; ANGIOGRAPHY; RECONSTRUCTION AB Purpose: To evaluate multi-slice spiral computed tomography (MSCT) for measurements of left ventricular volumes, ejection fraction (EF), and myocardial mass in comparison with electron beam CT (EBCT) as a reference method. Material and Methods: Six minipigs underwent both standardized contrast-enhanced MSCT (effective acquisition time per cardiac cycle 125.7 +/- 30.1 ms, reconstructed slice thickness 8 mm) and EBCT (acquisition time 50 ms, collimated slice thickness 8 mm). The contrast-to-noise ratio of the left ventricle was measured in each animal, and the contour sharpness of the myocardium was analyzed. Volumes (EDV, ESV, SV) ejection fraction (EF), and muscle mass were calculated by MSCT and by EBCT using the slice summation method. Results: MSCT had a higher contrast-to-noise ratio and delineated the myocardial contours more sharply than EBCT. There was a close linear correlation between both modalities for all parameters (EDV: r(p)=0.88, ESV: r(p)=0.91, SV: r(p)=0.85, EF: r(p)=0.93; mass: r(p)=0.90; P<0.05 each). MSCT slightly overestimated ESV and slightly underestimated SV and EF compared with EBCT (P<0.05 each). Conclusions: Image quality in MSCT is superior to that of EBCT. Functional parameters correlate well between both modalities, but the accuracy of MSCT is limited by its lower temporal resolution. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Charite Univ Med Berlin, Dept Radiol, Berlin, Germany. Humboldt Univ, Berlin, Germany. Free Univ Berlin, Sch Med, Berlin, Germany. RP Lembcke, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White Bldg,Room 270, Boston, MA 02114 USA. EM alexander.lembcke@gmx.de OI Hermann, Kay-Geert/0000-0001-6142-3814 NR 33 TC 6 Z9 8 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD DEC PY 2004 VL 45 IS 8 BP 819 EP 827 DI 10.1080/02841850410008720 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 883QW UT WOS:000226031800006 PM 15690611 ER PT J AU Becker, HC Lopez, MF AF Becker, HC Lopez, MF TI Increased ethanol drinking after repeated chronic ethanol exposure and withdrawal experience in C57BL/6 mice SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol drinking; ethanol dependence; withdrawal sensitization; C57BL/6J mice ID LIMITED ACCESS PARADIGM; PREFERRING P RAT; ALCOHOL-WITHDRAWAL; ANIMAL-MODEL; REPEATED DEPRIVATIONS; CONSUMPTION; PREFERENCE; DEPENDENCE; SEIZURES; EPISODES AB Background: The development of dependence may have significant motivational consequences regarding continued use and abuse of ethanol. We have developed a mouse model of ethanol dependence and repeated withdrawals that demonstrates sensitization of seizures and other symptoms of withdrawal. It is unclear whether such experience influences ethanol drinking behavior. The present series of experiments were designed to examine whether repeated cycles of chronic ethanol exposure and withdrawal has an impact on subsequent motivation to voluntarily self-administer ethanol. Methods: With the use of a modified sucrose-fading procedure, adult male C57BL/6J mice were trained to drink 15% (v/v) ethanol in a limited access procedure (2 hr/day). The animals were not food or water deprived at any time during the experiments. Once stable baseline intake was established, mice were exposed to four cycles of 16 hr of ethanol vapor (or air) in inhalation chambers separated by 8-hr periods of withdrawal. At 32 hr after the last cycle of ethanol exposure, all mice were tested for ethanol intake under limited access conditions for 5 consecutive days. The animals then received a second series of chronic ethanol exposure and withdrawal followed by another 5-day test period for ethanol drinking. Results: Stable daily baseline intake was established in mice that drank 15% ethanol combined with 5% sucrose (experiment 1), 15% ethanol alone (experiment 2), 5% sucrose alone (experiment 3), or 15% ethanol when presented as a choice with water (experiment 4). After repeated cycles of chronic ethanol exposure and withdrawal experience, consumption of ethanol solutions increased over baseline levels and in comparison with control (air-exposed) groups. However, sucrose consumption did not change in mice that were trained to drink 5% sucrose. The increase in ethanol consumption after chronic ethanol exposure and withdrawal experience resulted in a significant increase in resultant blood ethanol levels. Conclusions: Once the positive reinforcing properties of ethanol were established, chronic ethanol exposure and withdrawal experience resulted in a significant increase in voluntary ethanol drinking that yielded a >2-fold increase in resultant blood ethanol levels. This increase in ethanol intake occurred whether ethanol was presented in combination with sucrose, alone (unadulterated), or as a choice with tap water. Furthermore, this effect seems to be selective for ethanol in that animals that were trained to drink a sucrose solution did not exhibit a change in their intake after similar chronic ethanol exposure. As such, this model may be useful in studying the mechanisms and conditions in which chronic ethanol treatment influences motivation to resume drinking after a period of abstinence (relapse). C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Ralph H Johnson VA Med Ctr, Chareston Alcohol Res Ctr,Ctr Drug & Alcohol Prog, Charleston, SC 29425 USA. RP Becker, HC (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Ralph H Johnson VA Med Ctr, Chareston Alcohol Res Ctr,Ctr Drug & Alcohol Prog, IOP 456N,67 President St, Charleston, SC 29425 USA. EM beckerh@musc.edu FU NIAAA NIH HHS [AA013885, AA014095, P50-AA014095] NR 50 TC 161 Z9 162 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2004 VL 28 IS 12 BP 1829 EP 1838 DI 10.1097/01.ALC.0000149977.95306.3A PG 10 WC Substance Abuse SC Substance Abuse GA 881KI UT WOS:000225866000007 PM 15608599 ER PT J AU Pisegna, J Holtmann, G Howden, CW Katelaris, PH Sharma, P Spechler, S Triadafilopoulos, G Tytgat, G AF Pisegna, J Holtmann, G Howden, CW Katelaris, PH Sharma, P Spechler, S Triadafilopoulos, G Tytgat, G TI Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID HELICOBACTER-PYLORI INFECTION; DUODENAL-ULCER DISEASE; GASTRIC-ACID SECRETION; BARRETTS-ESOPHAGUS; ATROPHIC GASTRITIS; CHANGING PATTERNS; TREATING PATIENTS; THERAPY; GERD; RISK AB The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H-2-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310-30.). C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, Los Angeles, CA 90073 USA. Royal Adelaide Hosp, Dept Gastroenterol Hepatol & Gen Med, Adelaide, SA 5000, Australia. Northwestern Univ, Feinberg Sch Med, Div Gastroenterol, Chicago, IL 60611 USA. Univ Sydney, Dept Gastroenterol, Concord Hosp, Sydney, NSW 2006, Australia. Univ Kansas, Sch Med, VA Med Ctr, Kansas City, MO USA. Univ Texas, SW Med Ctr, Div Gastroenterol, Dallas, TX USA. Stanford Univ, Med Ctr, Div Gastroenterol & Hepatol, Menlo Pk, CA USA. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol, NL-1105 AZ Amsterdam, Netherlands. RP VA Greater Los Angeles Healthcare Syst, Div Gastroenterol & Hepatol, 691-111C, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu NR 81 TC 24 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 EI 1365-2036 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD DEC PY 2004 VL 20 SU 9 BP 47 EP 56 DI 10.1111/j.1365-2036.2004.02240.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 868NU UT WOS:000224921100006 PM 15527464 ER PT J AU Baruch, L Glazer, RD Aknay, N Vanhaecke, J Heywood, JT Anand, I Phil, D Krum, H Hester, A Cohn, JN AF Baruch, L Glazer, RD Aknay, N Vanhaecke, J Heywood, JT Anand, I Phil, D Krum, H Hester, A Cohn, JN TI Morbidity, mortality, physiologic and functional parameters in elderly and non-elderly patients in the Valsartan Heart Failure Trial (Val-HeFT) SO AMERICAN HEART JOURNAL LA English DT Article ID ANGIOTENSIN-RECEPTOR BLOCKER; CONVERTING ENZYME-INHIBITORS; HOSPITALIZATION; HYPERTENSION; ALDOSTERONE; POPULATION; GUIDELINES; SURVIVAL AB Background The Valsartan Heart Failure Trial (Val-HeFT) demonstrated the favorable effects of the addition of valsartan to prescribed heart failure (HF) therapy on HF hospitalization, and functional and physiological parameters. As the prevalence of HF morbidity and mortality are increased in the elderly, the effect of valsartan in the elderly is oil clinical significance. Methods In this post-hoc analysis, morbidity, mortality, left ventricular (LV) size and function, brain natriuretic peptide (BNP), aldosterone, norepinephrine (NE), quality of life, and treatment effect with valsartan were examined by subgroups of 2350 elderly (greater than or equal to65 years) and 2660 non-elderly (<65 years) patients enrolled in Val-HeFT. Results while the overall incidence of morbidity and mortality was higher in the elderly, valsartan produced beneficial effects in reducing risk of morbidity in the elderly by 11.8% (P = .07), and the non-elderly by 14.6% (P = .09). Valsartan had no effect on mortality compared to placebo in the non-elderly, 15.2% vs 15.0% (P = .87), and elderly,, 25.1% vs 24.0%, (P = .64). Valsartan had statistically significant beneficial effects in both the elderly and non-elderly or, LV size and function, BNP, aldosterone and quality of life. Beneficial effects on NE were also observed with valsartan, in both subgroups with statistically significant reductions produced in the non-elderly. Conclusions Val-HeFT demonstrated that elderly patients present with more advanced HF as evidenced by higher morbidity and mortality along with greater neurohormonal activation. In Val-HeFT, valsartan produced G consistent beneficial effect on morbidity, LV function and size, quality of life, and neurohormonal levels in both the elderly and non-elderly. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. UZ Gasthuisberg, Louvain, Belgium. Loma Linda Univ, Med Ctr, Loma Linda, CA USA. Vet Affairs Med Ctr, Minneapolis, MN USA. Monash Univ, Sch Med, Alfred Hosp, Melbourne, Vic 3004, Australia. Univ Minnesota, Minneapolis, MN USA. RP Baruch, L (reprint author), Bronx Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM baruchlarry@att.net NR 22 TC 14 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2004 VL 148 IS 6 BP 951 EP 957 DI 10.1016/j.ahj.2004.06.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 882WF UT WOS:000225970400006 PM 15632877 ER PT J AU Schernhammer, ES Hankinson, SE Rosner, B Kroenke, CH Willett, WC Colditz, GA Kawachi, I AF Schernhammer, ES Hankinson, SE Rosner, B Kroenke, CH Willett, WC Colditz, GA Kawachi, I TI Job stress and breast cancer risk - The nurses' health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast neoplasms; hormones; occupational exposure; stress; workplace ID CORONARY-HEART-DISEASE; PSYCHOSOCIAL WORK CHARACTERISTICS; NATIONAL DEATH INDEX; ADVERSE LIFE-EVENTS; CARDIOVASCULAR-DISEASE; UNITED-STATES; MYOCARDIAL-INFARCTION; DECISION LATITUDE; RESTRAINT STRESS; SOCIAL SUPPORT AB Workers tend to perceive certain features of their jobs as harmful to health and are alert to associations between job stress and health outcomes, but few observational studies have evaluated the role of job stress in carcinogenesis. The authors prospectively assessed the association between job strain, measured by Karasek and Theorell's job content questionnaire in four categories (low strain, active, passive, and high strain), and breast cancer risk among participants in the Nurses' Health Study. A total of 37,562 US female registered nurses were followed for up to 8 years (1992-2000), and 1,030 cases of invasive breast cancer were ascertained during that period. All participants were still in the workforce at baseline and completed the job content questionnaire. Adjusted for age, reproductive history, and other breast cancer risk factors, the multivariate relative risks of breast cancer, in comparison with women who worked in low-strain jobs, were 0.83 (95% confidence interval (CI): 0.69, 0.99) for women in active jobs, 0.87 (95% CI: 0.73, 1.04) for women in high-strain jobs, and 0.90 (95% CI: 0.76, 1.06) for women in passive jobs. Findings from this study indicate that job stress is not related to any increase in breast cancer risk. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc Res, Vienna, Austria. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Program Epidemiol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Schernhammer, ES (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA49449, CA/ES62984, CA87969]; NHLBI NIH HHS [HL-03453] NR 50 TC 39 Z9 40 U1 0 U2 14 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 DEC 1 PY 2004 VL 160 IS 11 BP 1079 EP 1086 DI 10.1093/aje/kwh327 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 874PC UT WOS:000225361300006 PM 15561987 ER PT J AU Wang, S Degar, BA Zieske, A Shafi, NQ Rose, MG AF Wang, S Degar, BA Zieske, A Shafi, NQ Rose, MG TI Hemophagocytosis exacerbated by G-CSF/GM-CSF treatment in a patient with myelodysplasia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE hemophagocytosis; thrombophagocytosis; G-CSF; GM-CSF; myelodysplasia; splenectomy ID COLONY-STIMULATING FACTOR; ACUTE MYELOBLASTIC-LEUKEMIA; EXTENSIVE ERYTHROPHAGOCYTOSIS; CYCLOSPORINE-A; FACTOR THERAPY; LYMPHOHISTIOCYTOSIS; ERYTHROPOIETIN; ASSOCIATION; CHILDREN; VARIANT AB We describe a 75-year-old man with neutropenia in whom bone marrow aspirate and biopsy demonstrated hemophagocytosis associated with myelodysplasia (MDS). Therapy with granulocyte-colony stimulating factor (G-CSF) and granulocyte-monocyte-colony stimulating factor (GM-CSF) caused splenomegaly and severe thrombocytopenia, which recurred upon rechallenge. We propose that myeloid growth factors may be detrimental in patients with MDS-associated hemophagocytosis. (C) 2004 Wiley-Liss, Inc. C1 VA Connecticut Healthcare Syst, IIID, Ctr Canc, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Vet Adm Connecticut Healthcare Syst, Dept Med, West Haven, CT USA. RP Rose, MG (reprint author), VA Connecticut Healthcare Syst, IIID, Ctr Canc, 950 Campbell Ave, West Haven, CT 06516 USA. EM Michal.Rose@med.va.gov NR 33 TC 17 Z9 18 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2004 VL 77 IS 4 BP 391 EP 396 DI 10.1002/ajh.20202 PG 6 WC Hematology SC Hematology GA 875TL UT WOS:000225444600017 PM 15551287 ER PT J AU Wang, PL Meyer, MM Orloff, SL Anderson, S AF Wang, PL Meyer, MM Orloff, SL Anderson, S TI Bone resorption and "relative" immobilization hypercalcemia with prolonged continuous renal replacement therapy and citrate anticoagulation SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE continuous renal replacement therapy (CRRT); immobilization hypercalcemia; citrate; osteoporosis ID CRITICALLY ILL PATIENT; CALCIUM HOMEOSTASIS; ELDERLY-PATIENTS; HEMOFILTRATION; OSTEOPOROSIS; METABOLISM AB Regional citrate anticoagulation is an alternative to heparin in patients with bleeding diatheses who require continuous renal replacement therapy (CRRT). The short-term metabolic consequences that occur with citrate anticoagulation are well described and usually manageable if established protocols are followed vigilantly. Because of its customary short-term nature, the long-term consequences of CRRT with citrate are less often considered and have not been reported. The authors present the case of a woman with multisystem organ failure and prolonged acute renal failure who required CRRT for 120 days. Throughout her hospital course, adequate regional anticoagulation was achieved by blocking the coagulation cascade via the chelation of calcium by citrate. Despite an appropriate drop in the postfilter ionized calcium level, by 8 weeks after the initiation of CRRT, the patient was able to normalize serum calcium levels without the customary calcium infusion. Bone resorption owing to prolonged immobilization leading to hypercalcemia is a known complication of critically ill patients. This problem is more pronounced in patients with high bone turnover rates owing to conditions such as secondary hyperparathyroidism. In this particular case, the chelation of calcium by citrate masked the ensuing immobilization hypercalcemia, resulting in marked bone loss and bilateral spontaneous femoral fractures in the context of normal calcium levels. In critically ill patients sustained with prolonged CRRT with citrate anticoagulation, bone resorption and "relative" immobilization hypercalcemia may manifest as normal serum calcium levels in the face of failing calcium infusion rate requirements. Am J Kidney Dis 44:1110-1114. (C) 2004 by the National Kidney Foundation, Inc. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Dept Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Surg, Div Liver Pancreas Transplantat, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens PP262, 3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM anderssh@ohsu.edu NR 17 TC 7 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2004 VL 44 IS 6 BP 1110 EP 1114 DI 10.1053/j.ajkd.2004.09.001 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 877SO UT WOS:000225590700019 PM 15558534 ER PT J AU Lin, AE Belmont, J Salbert, BA Salbert, BA AF Lin, AE Belmont, J Salbert, BA Salbert, BA TI Total is more than the sum of the parts: Phenotyping the heart in cardiovascular genetics clinics SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Editorial Material C1 MassGen Hosp Children, Genet & Teratol Unit, Boston, MA 02114 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Univ Rochester, Med Ctr, Golisano Childrens Hosp Strong, Rochester, NY 14642 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. RP Lin, AE (reprint author), MassGen Hosp Children, Genet & Teratol Unit, Warren 801, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu OI Belmont, John/0000-0001-7409-3578 NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD DEC 1 PY 2004 VL 131A IS 2 BP 111 EP 114 DI 10.1002/ajmg.a.30304 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 876WS UT WOS:000225530000001 PM 15487010 ER PT J AU Landefeld, CS AF Landefeld, CS TI Commercial support and bias in pharmaceutical research SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID CONFLICTS-OF-INTEREST; DRUG TRIALS; INDUSTRY; ASSOCIATION; PHYSICIANS; INTERESTS; COMPANIES; QUALITY; EVENTS C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94118 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Div Geriatr, Box 1265,Suite 380,3333 Calif St, San Francisco, CA 94118 USA. NR 23 TC 5 Z9 5 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 1 PY 2004 VL 117 IS 11 BP 876 EP 878 DI 10.1016/j.amjmed.2004.10.001 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 879GH UT WOS:000225703900013 PM 15589496 ER PT J AU Tracy, EE Jagsi, R Starr, R Tarbell, NJ AF Tracy, EE Jagsi, R Starr, R Tarbell, NJ TI Outcomes of a pilot faculty mentoring program SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE mentoring; faculty; promotion ID ACADEMIC MEDICINE; WOMEN; SUCCESS; CAREER AB Objective: The purpose of this Study was to determine whether a junior faculty mentoring program is beneficial to participants and to identify particular positive and negative aspects of such a program to enable others to institute similar programs. Study design: In 2001 a pilot program was instituted in our obstetrics and gynecology department for interested faculty members. There were 3 focus groups and a written survey that assessed the project. A combination of qualitative and quantitative methods were used for data analysis; Fisher's exact test was used. Results: Two recurring themes emerged from the focus group sessions: participants felt better supported by the department and appreciated a greater sense of camaraderie. Most mentees noted the program's success in the following areas of having a role model (83.3%), having increased visibility (82.3%), and having to whom someone to turn (93.8%). Conclusion: The faculty mentoring program had significant benefits for everyone who participated. (C) 2004 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Dept, Boston, MA 02114 USA. RP Tracy, EE (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Dept, Founders 406,Fruit St, Boston, MA 02114 USA. EM EETracy@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 21 TC 32 Z9 32 U1 2 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 BP 1846 EP 1850 DI 10.1016/j.ajog.2004.08.002 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FZ UT WOS:000225925800002 PM 15592263 ER PT J AU Allen, R Benson, C Wilkins-Haug, L AF Allen, R Benson, C Wilkins-Haug, L TI Pregnancy outcome of fetuses diagnosed with hypoplastic left ventricle on prenatal sonogram SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Maternal Fetal Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 575 BP S163 EP S163 DI 10.1016/j.ajog.2004.10.477 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500569 ER PT J AU Chang, E Barbosa, E Singh, I Singh, A Paintilia, M AF Chang, E Barbosa, E Singh, I Singh, A Paintilia, M TI The effects of treatment with N-acetylcysteine (NAC) in a rat model of preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 12 BP S6 EP S6 DI 10.1016/j.ajog.2004.09.047 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500014 ER PT J AU Levine, R Thadhani, R Qian, C Lam, C Lim, KH Yu, K Blink, A Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A AF Levine, R Thadhani, R Qian, C Lam, C Lim, KH Yu, K Blink, A Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A TI Urinary placental growth factor (PGF) and the risk of preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 09-12, 2005 CL Reno, NV SP Soc Maternal Fetal Med C1 NICHHD, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Allied Technol Grp, Rockville, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2004 VL 191 IS 6 SU S MA 10 BP S6 EP S6 DI 10.1016/j.ajog.2004.09.045 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 882FW UT WOS:000225925500012 ER PT J AU Rubin, PAD Foster, CS AF Rubin, PAD Foster, CS TI Etiology and management of idiopathic orbital inflammation SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID TNF-ALPHA; FIBROBLASTS; THERAPY; LESIONS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM eye_Plastics@meei.harvard.edu NR 12 TC 33 Z9 39 U1 0 U2 1 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 DEC PY 2004 VL 138 IS 6 BP 1041 EP 1043 DI 10.1016/j.ajo.2004.09.032 PG 3 WC Ophthalmology SC Ophthalmology GA 882TC UT WOS:000225960200020 PM 15629299 ER PT J AU Polanczyk, MJ Jones, RE Subramanian, S Afentoulis, M Rich, C Zakroczymski, M Cooke, P Vandenbark, AA Offner, H AF Polanczyk, MJ Jones, RE Subramanian, S Afentoulis, M Rich, C Zakroczymski, M Cooke, P Vandenbark, AA Offner, H TI T lymphocytes do not directly mediate the protective effect of estrogen on experimental autoimmune encephalomyelitis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS; ANTIGEN PRESENTATION; LEUKOCYTE ADHESION; MICE; CELLS; EXPRESSION; RECEPTORS; PREGNANCY; INJURY AB Gender influences mediated by 17beta-estradiol (E2) have been associated with susceptibility to and severity of autoimmune diseases such as diabetes, arthritis, and multiple sclerosis. in this regard, we have shown that estrogen receptor-alpha (Esr1) is crucial for the protective effect of 17beta-estradiol (E2) in murine experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis. The expression of estrogen receptors among various immune cells (eg, T and B lymphocytes, antigen-presenting cells) suggests that the therapeutic effect of E2 is likely mediated directly through specific receptor binding. However, the target immune cell populations responsive to E2 treatment have not been identified. in the current study, we induced EAE in T-cell-deficient, severe combined immunodeficient mice or in immunocompetent mice with encephalitogenic T cells from wildtype Esr1 +/+ or Esr1 knockout (Esr1 -/-) donors and compared the protective E2 responses. The results showed that E2-responsive, Esr1] +/+ disease-inducing encephalitogenic T cells were neither necessary nor sufficient for E2-mediated protection from EAE. Instead, the therapeutic response appeared to be mediated through direct effects on nonlymphocytic, E2-responsive cells and down-regulation of the inflammatory response in the central nervous system. These results provide the first demonstration that the protective effect of E2 on EAE is not mediated directly through E2-responsive T cells and raise the alternative possibility that nonlymphocytic cells such as macrophages, dendritic cells, or other nonlymphocytic cells are primarily responsive to E2 treatment in EAE. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Univ Illinois, Urbana, IL 61801 USA. Agr Univ Warsaw, Fac Med Vet, Dept Food Hyg, Warsaw, Poland. RP Offner, H (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D-31, Portland, OR 97239 USA. EM offnverva@ohsu.edu FU NIEHS NIH HHS [ES11590, R01 ES011590]; NINDS NIH HHS [NS23444, NS23221, NS39122, NS45445, R01 NS023221, R01 NS023444, R01 NS039122, R01 NS045445] NR 36 TC 39 Z9 42 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2004 VL 165 IS 6 BP 2069 EP 2077 DI 10.1016/S0002-9440(10)63257-9 PG 9 WC Pathology SC Pathology GA 874WL UT WOS:000225381100021 PM 15579449 ER PT J AU Park, YW Kang, YM Butterfield, J Detmar, M Goronzy, JJ Weyand, CM AF Park, YW Kang, YM Butterfield, J Detmar, M Goronzy, JJ Weyand, CM TI Thrombospondin 2 functions as an endogenous regulator of angiogenesis and inflammation in rheumatoid arthritis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; T-CELLS; TUMOR-GROWTH; MATRICELLULAR PROTEIN; GERMINAL-CENTERS; SYNOVIAL TISSUE; END-STAGE; MICE; ACTIVATION; EXPRESSION AB Thrombospondin 2 (TSP2), a matricellular protein with a primary role in modulating cell-matrix interactions, has been implicated in tissue repair and foreign body responses. Here we show that TSP2 has regulatory function in the chronic inflammatory lesions of rheumatoid arthritis. Tissue TSP2, produced by synovial fibroblasts, endothelial cells, and macrophages correlated not only with the intensity of angiogenesis but also with the architecture of lymphoid infiltrates. Synovial tissues with diffuse inflammatory infiltrates had high levels of TSP2, whereas synovial tissues with ectopic germinal center reactions and T cell-B cell aggregates produced low levels. Cell-based gene therapy with TSP2 was used to examine the in vivo effects of the matrix protein on neoangiogenesis and lymphoid organization. Human synovium-severe combined immunodeficiency (SCID)) mouse chimeras were treated with TSP2-transfected fibroblasts deposited into the peritoneum. Overexpression of TSP2 led to the accumulation of TSP2 protein in the inflamed synovium and resulted in a prompt inhibition of lesional. vascularization. Beside its anti-angiogenic activity, TSP2 also suppressed the production of the proinflammatory mediators, hiterferon-gamma and tumor necrosis factor-alpha, and induced the depletion of tissue-residing T cells. We propose that TSP2 is an endogenous regulator of angiogenesis and autoimmune inflammation in the synovium and represents a protective mechanism preventing ectopic lympho-organogenesis and persistent inflammation in this tissue site. C1 Emory Univ, Sch Med, Lowance Ctr Human Immunol, Dept Med, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weyand, CM (reprint author), Emory Univ, Sch Med, Lowance Ctr Human Immunol, Dept Med, Room 1014,Woodruff Mem Res Bldg,101 Woodruff Circ, Atlanta, GA 30322 USA. EM cweyand@emory.edu FU NEI NIH HHS [R01 EY011916, R01 EY 11916]; NIAID NIH HHS [R01 AI044142, R01 AI 44142]; NIAMS NIH HHS [R01 AR 41974, R01 AR042527, R01 AR 42527, R01 AR041974] NR 56 TC 54 Z9 58 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2004 VL 165 IS 6 BP 2087 EP 2098 DI 10.1016/S0002-9440(10)63259-2 PG 12 WC Pathology SC Pathology GA 874WL UT WOS:000225381100023 PM 15579451 ER PT J AU Kyriakides, TR Foster, MJ Keeney, GE Tsai, A Giachelli, CM Clark-Lewis, I Rollins, BJ Bornstein, P AF Kyriakides, TR Foster, MJ Keeney, GE Tsai, A Giachelli, CM Clark-Lewis, I Rollins, BJ Bornstein, P TI The CC chemokine ligand, CCL2/MCP1, participates in macrophage fusion and foreign body giant cell formation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHEMOATTRACTANT PROTEIN-1 MCP-1; GENE DELIVERY; MICE; BIOMATERIALS; RECEPTOR; IDENTIFICATION; ANGIOGENESIS; INHIBITOR; RESPONSES; ADHESION AB The foreign body reaction (FBR) develops in response to the implantation of almost all biomaterials and can be detrimental to their function. The formation of foreign body giant cells (FBGC), which damage the surface of biomaterials, is considered a hallmark of this reaction. FBGC derive from blood-borne monocytes that enter the implantation site after surgery in response to the release of chemotactic signals. in this study, we implanted biomaterials subcutaneous (s.c.) in mice that lack the monocyte chemoattractant CC chemokine ligand 2 (CCL2) and found that biomaterials were encapsulated despite reduced FBGC formation. The latter was due to compromised macrophage fusion rather than migration. Consistent with the reduction in FBGC formation, biodegradable biomaterials sustained reduced damage in CCL2-null mice. Furthermore, blockade of CCL2 function by localized gene delivery in wild-type mice hindered FBGC formation, despite normal monocyte recruitment. The requirement for CCL2 in fusion was confirmed by the ability of both a CCL2 inhibitory peptide and an anti-CCL2 Ab to reduce FBGC formation from peripheral blood monocytes in an in vitro assay. Our findings demonstrate a previously unreported involvement of CCL2 in FBGC formation, and suggest that FBGC are not the primary determinants of capsule formation in the FBR. C1 Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kyriakides, TR (reprint author), Yale Univ, Sch Med, Dept Pathol & Biomed Engn, POB 9812, New Haven, CT 06536 USA. FU NIAMS NIH HHS [AR 45418, R01 AR045418] NR 42 TC 104 Z9 109 U1 0 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2004 VL 165 IS 6 BP 2157 EP 2166 DI 10.1016/S0002-9440(10)63265-8 PG 10 WC Pathology SC Pathology GA 874WL UT WOS:000225381100029 PM 15579457 ER PT J AU Andrews, NC AF Andrews, NC TI Probing the iron pool. Focus on " Detection of intracellular iron by its regulatory effect" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material C1 Harvard Univ, Childrens Hosp, Karp Family Res Labs 8 125, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Harvard Univ, Childrens Hosp, Karp Family Res Labs 8 125, Sch Med, 300 Longwood Ave, Boston, MA 02115 USA. EM nandrews@enders.tch.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 NR 3 TC 9 Z9 9 U1 0 U2 0 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 DEC PY 2004 VL 287 IS 6 BP C1537 EP C1538 DI 10.1152/ajpcell.00435.2004 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867WV UT WOS:000224874400003 PM 15525686 ER PT J AU Wisse, BE Ogimoto, K Morton, GJ Wilkinson, CW Frayo, RS Cummings, DE Schwartz, MW AF Wisse, BE Ogimoto, K Morton, GJ Wilkinson, CW Frayo, RS Cummings, DE Schwartz, MW TI Physiological regulation of hypothalamic IL-1 beta gene expression by leptin and glucocorticoids: implications for energy homeostasis SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE interleukin-1 beta; cytokine; corticosterone; food intake; appetite; obesity; anorexia ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; FOOD-INTAKE; RAT-BRAIN; INTERLEUKIN-1-BETA; MECHANISMS; RECEPTORS; CORTICOSTERONE; ACTIVATION; CYTOKINES AB Interleukin-1beta (IL-1beta) is synthesized in a variety of tissues, including the hypothalamus, where it is implicated in the control of food intake. The current studies were undertaken to investigate whether hypothalamic IL-1beta gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1beta mRNA levels twofold, measured by real-time PCR (P < 0.05 vs. sham-operated controls), and this effect was blocked by subcutaneous infusion of a physiological dose of corticosterone. Conversely, hypothalamic IL-1β mRNA levels were reduced by 30% in fa/fa (Zucker) rats, a model of genetic obesity caused by leptin receptor mutation (P = 0.01 vs. lean littermates), and the effect of ADX to increase hypothalamic IL-1β mRNA levels in fa/fa rats (P = 0.02) is similar to that seen in normal animals. Moreover, fasting for 48 h (which lowers leptin and raises corticosterone levels) reduced hypothalamic IL-1β mRNA levels by 30% (P = 0.02), and this decrease was fully reversed by refeeding for 12 h. Thus leptin and GCs exert opposing effects on hypothalamic IL-1β gene expression, and corticosterone plays a physiological role to limit expression of this cytokine in both the presence and absence of intact leptin signaling. Consistent with this hypothesis, systemic leptin administration to normal rats (2 mg/kg ip) increased hypothalamic IL-1β mRNA levels twofold (P < 0.05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1beta is subject to opposing physiological regulation by corticosterone and leptin. C1 Univ Washington, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Wisse, BE (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Metab Endocrinol & Nutr, 325 9th Ave,Box 359757, Seattle, WA 98104 USA. EM bewisse@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK 12819, DK 52989, DK 61384, DK 61516, P30 DK 035816, P30 DK 17047]; NINDS NIH HHS [NS 32273] NR 30 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2004 VL 287 IS 6 BP E1107 EP E1113 DI 10.1152/ajpendo.00038.2004 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 867WP UT WOS:000224873800010 PM 15304373 ER PT J AU Fischer, L Gukovskaya, AS Young, SH Gukovsky, I Lugea, A Buechler, P Penninger, JM Friess, H Pandol, SJ AF Fischer, L Gukovskaya, AS Young, SH Gukovsky, I Lugea, A Buechler, P Penninger, JM Friess, H Pandol, SJ TI Phosphatidylinositol 3-kinase regulates Ca2+ signaling in pancreatic acinar cells through inhibition of sarco(endo)plasmic reticulum Ca2+-ATPase SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pancreas; cholecystokinin; carbachol ID ADENINE-DINUCLEOTIDE PHOSPHATE; CASEIN KINASE-II; INOSITOL 1,4,5-TRISPHOSPHATE; CYTOSOLIC CALCIUM; HUMAN PLATELETS; MAST-CELLS; ACTIVATION; STORES; ENTRY; CHOLECYSTOKININ AB Calcium is a key mediator of hormone-induced enzyme secretion in pancreatic acinar cells. At the same time, abnormal Ca2+ responses are associated with pancreatitis. We have recently shown that inhibition of phosphatidylinositol 3-kinase (PI3-kinase) by LY-294002 and wortmannin, as well as genetic deletion of PI3-kinase-gamma, regulates Ca2+ responses and the Ca2+-sensitive trypsinogen activation in pancreatic acinar cells. The present study sought to determine the mechanisms of PI3-kinase involvement in Ca2+ responses induced in these cells by CCK and carbachol. The PI3-kinase inhibitors inhibited both Ca2+ influx and mobilization from intracellular stores induced by stimulation of acini with physiological and pathological concentrations of CCK, as well as with carbachol. PI3-kinase inhibition facilitated the decay of cytosolic free Ca2+ concentration ([Ca2+](i)) oscillations observed in individual acinar cells. The PI3-kinase inhibitors decreased neither CCK-induced inositol 1,4,5-trisphosphate [Ins(1,4,5) P-3] production nor Ins(1,4,5) P-3-induced Ca2+ mobilization, suggesting that the effect of PI3-kinase inhibition is not through Ins( 1,4,5) P3 or Ins( 1,4,5) P3 receptors. PI3-kinase inhibition did not affect Ca2+ mobilization induced by thapsigargin, a specific inhibitor of sarco(endo) plasmic reticulum Ca2+-ATPase (SERCA). Moreover, SERCA blockade with thapsigargin abolished the effects of pharmacological and genetic PI3-kinase inhibition on [Ca2+](i) signals, suggesting SERCA as a downstream target of PI3-kinase. Both pharmacological PI3-kinase inhibition and genetic deletion of PI3-kinase-gamma increased the amount of Ca2+ in intracellular stores during CCK stimulation. Finally, addition of the PI3-kinase product phosphatidylinositol 3,4,5-trisphosphate to permeabilized acini significantly attenuated Ca2+ reloading into the endoplasmic reticulum. The results indicate that PI3-kinase regulates Ca2+ signaling in pancreatic acinar cells through its inhibitory effect on SERCA. C1 Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Heidelberg, Dept Surg, D-69120 Heidelberg, Germany. Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Vet Affairs Healthcare Ctr, 11301 Wilshire Blvd,Bldg 258,Rm 340, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 FU NIAAA NIH HHS [P50-AA-11999]; NIDDK NIH HHS [DK-59508, DK-59936] NR 58 TC 18 Z9 19 U1 0 U2 3 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 DEC PY 2004 VL 287 IS 6 BP G1200 EP G1212 DI 10.1152/ajpgi.00212.2004 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 869MI UT WOS:000224987400013 PM 15271649 ER PT J AU Hartwig, W Werner, J Warshaw, AL Antoniu, B Fernandez-del Castillo, C Gebhard, MM Uhl, W Buchler, MW AF Hartwig, W Werner, J Warshaw, AL Antoniu, B Fernandez-del Castillo, C Gebhard, MM Uhl, W Buchler, MW TI Membrane-bound ICAM-1 is upregulated by trypsin and contributes to leukocyte migration in acute pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the International-Association-of-Pancreatology/European-Pancreas-Club CY JUN 19-22, 2002 CL Heidelberg, GERMANY SP Int Assoc Pancreatol, European Pancreas Club DE adhesion molecules; endothelial cells; proteases; systemic inflammatory response syndrome ID INTERCELLULAR-ADHESION MOLECULE-1; DIET-INDUCED PANCREATITIS; LUNG INJURY; NECROTIZING PANCREATITIS; NEUTROPHIL SEQUESTRATION; CIRCULATING ICAM-1; PULMONARY ICAM-1; EXPRESSION; ACTIVATION; PLASMA AB In acute pancreatitis, ICAM-1 is upregulated in various organs and contributes to the development of organ injury. To investigate the effects of pancreatic proteases on ICAM-1 expression and their role in the early process of leukocyte migration, human umbilical vein endothelial cells (HUVECs) were incubated with serum subjected to limited trypsin digestion and Wistar rats were injected with trypsin. Significant upregulation of membrane-bound ICAM-1 was seen on HUVECs incubated with trypsinated serum. Likewise, soluble ICAM-1 increased in the supernatant of HUVECs. Changes of membrane-bound ICAM-1 and soluble ICAM-1 were maximal with high concentrations of trypsin. HUVECs incubated with TNF-alpha (positive control) showed similar changes. In the pancreas and lungs of animals infused with trypsin, ICAM-1 and leukocyte sequestration were increased compared with controls. Reflecting the relevance of protease-induced ICAM-1 expression in leukocyte migration, leukocyte-endothelium interaction, as assessed by intravital microscopy, was markedly increased by trypsin. Inhibition of ICAM-1 ameliorated these changes significantly. In conclusion, trypsinated serum induces the upregulation of both membrane-bound ICAM-1 on endothelial cells and soluble ICAM-1. These changes contribute to the early steps of leukocyte migration in acute pancreatitis. The role of soluble ICAM-1 remains to be investigated. C1 Univ Heidelberg, Dept Gen Surg, D-69120 Heidelberg, Germany. Univ Heidelberg, Dept Expt Surg, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Buchler, MW (reprint author), Univ Heidelberg, Dept Gen Surg, Neuenheimer Feld 110, D-69120 Heidelberg, Germany. EM markus_buechler@med.uni-heidelberg.de NR 42 TC 23 Z9 24 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 DEC PY 2004 VL 287 IS 6 BP G1194 EP G1199 DI 10.1152/ajpgi.00221.2004 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 869MI UT WOS:000224987400012 PM 15308472 ER PT J AU Minneci, PC Deans, KJ Banks, SM Costello, R Csako, G Eichacker, PQ Danner, RL Natanson, C Solomon, SB AF Minneci, PC Deans, KJ Banks, SM Costello, R Csako, G Eichacker, PQ Danner, RL Natanson, C Solomon, SB TI Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE vasopressors and systemic perfusion; low cardiac output septic shock; vasopressors and acidosis; vasopressors and cardiac function ID LOW-DOSE VASOPRESSIN; REVERSIBLE MYOCARDIAL DEPRESSION; BETA-ADRENERGIC RECEPTORS; HEMODYNAMIC SUPPORT; HEART-FAILURE; SEPSIS; THERAPY; POLYSACCHARIDE; EPIDEMIOLOGY; DYSFUNCTION AB During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 mug.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 mug.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P<0.06), mean arterial pressure (MAP) (P<0.05), cardiac index (CI) (P<0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, 10 Ctr Dr,Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 51 TC 15 Z9 16 U1 0 U2 3 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 DEC PY 2004 VL 287 IS 6 BP H2545 EP H2554 DI 10.1152/ajpheart.00450.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 871VW UT WOS:000225165700022 PM 15319205 ER PT J AU Beppu, H Ichinose, F Kawai, N Jones, RC Yu, PB Zapol, WM Miyazono, K Li, E Bloch, KD AF Beppu, H Ichinose, F Kawai, N Jones, RC Yu, PB Zapol, WM Miyazono, K Li, E Bloch, KD TI BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary vasculature; smooth muscle cells; bone morphogenetic protein; hypoxia ID BONE MORPHOGENETIC PROTEIN; SMOOTH-MUSCLE-CELLS; TGF-BETA FAMILY; RECEPTOR-II; SIGNAL-TRANSDUCTION; GERMLINE MUTATIONS; LUNG DEVELOPMENT; GENE-EXPRESSION; ARTERY SMOOTH; NITRIC-OXIDE AB Heterozygous mutations of the bone morphogenetic protein type II receptor (BMPR-II) gene have been identified in patients with primary pulmonary hypertension. The mechanisms by which these mutations contribute to the pathogenesis of primary pulmonary hypertension are not fully elucidated. To assess the impact of a heterozygous mutation of the BMPR-II gene on the pulmonary vasculature, we studied mice carrying a mutant BMPR-II allele lacking exons 4 and 5 (BMPR-II+/- mice). BMPR-II+/- mice had increased mean pulmonary arterial pressure and pulmonary vascular resistance compared with their wild-type littermates. Histological analyses revealed that the wall thickness of muscularized pulmonary arteries (<100 μm in diameter) and the number of alveolar-capillary units were greater in BMPR-II+/- than in wild-type mice. Breathing 11% oxygen for 3 wk increased mean pulmonary arterial pressure, pulmonary vascular resistance, and hemoglobin concentration to similar levels in BMPR-II+/- and wild-type mice, but the degree of muscularization of small pulmonary arteries and formation of alveolar-capillary units were reduced in BMPR-II+/- mice. Our results suggest that, in mice, mutation of one copy of the BMPR-II gene causes pulmonary hypertension but impairs the ability of the pulmonary vasculature to remodel in response to prolonged hypoxic breathing. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 1708455, Japan. RP Beppu, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, 149 13th St, Charlestown, MA 02129 USA. EM beppu@cvrc.mgh.harvard.edu OI Yu, Paul/0000-0003-2145-4944 FU NHLBI NIH HHS [HL-42397, HL-71987, HL-74352]; NICHD NIH HHS [HD-35286] NR 36 TC 116 Z9 118 U1 1 U2 5 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 DEC PY 2004 VL 287 IS 6 BP L1241 EP L1247 DI 10.1152/ajplung.00239.2004 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 869BI UT WOS:000224956900023 PM 15286002 ER PT J AU Simon, NM Otto, MW Wisniewski, SR Fossey, M Sagduyu, K Frank, E Sachs, GS Nierenberg, AA Thase, ME Pollack, MH AF Simon, NM Otto, MW Wisniewski, SR Fossey, M Sagduyu, K Frank, E Sachs, GS Nierenberg, AA Thase, ME Pollack, MH CA STEP-BD Investigators TI Anxiety disorder comorbidity in bipolar disorder patients: Data from the first 500 participants in the systematic treatment enhancement program for bipolar disorder (STEP-BD) SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 156th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 2003 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID PANIC DISORDER; I DISORDER; PSYCHIATRIC-DISORDERS; PSYCHOTIC FEATURES; SPECTRUM; EPIDEMIOLOGY; POPULATION; PREVALENCE; LIFETIME; SUICIDE AB Objective: The authors provide a detailed perspective on the correlates of comorbid anxiety in a large, well-characterized sample of bipolar disorder patients. Method: Anxiety and its correlates were examined in a cross-sectional sample from the first 500 patients with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder, a multicenter project funded by the National Institute of Mental Health designed to evaluate the longitudinal outcome of patients with bipolar disorder. Results: Lifetime comorbid anxiety disorders were common, occurring in over one-half of the sample, and were associated with younger age at onset, decreased likelihood of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Although substance abuse disorders were particularly prevalent among patients with anxiety disorders, comorbid anxiety appeared to exert an independent, deleterious effect on functioning, including history of suicide attempts (odds ratio=2.45, 95% CI=1.4-4.2). Conclusions: An independent association of comorbid anxiety with greater severity and impairment in bipolar disorder patients was demonstrated, highlighting the need for greater clinical attention to anxiety in this population, particularly for enhanced clinical monitoring of suicidality. in addition, it is important to determine whether effective treatment of anxiety symptoms can lessen bipolar disorder severity, improve response to treatment of manic or depressive symptoms, or reduce suicidality. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Wang ACC 815,15 Parkman St, Boston, MA 02114 USA. EM nsimon@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01 MH-80001] NR 27 TC 290 Z9 294 U1 2 U2 11 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 DEC PY 2004 VL 161 IS 12 BP 2222 EP 2229 DI 10.1176/appi.ajp.161.12.2222 PG 8 WC Psychiatry SC Psychiatry GA 876NJ UT WOS:000225503500013 PM 15569893 ER PT J AU Najib, A Lorberbaum, JP Kose, S Bohning, DE George, MS AF Najib, A Lorberbaum, JP Kose, S Bohning, DE George, MS TI Regional brain activity in women grieving a romantic relationship breakup SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2002 CL PHILADELPHIA, PA SP Soc Biol Psychiat ID CEREBRAL-BLOOD-FLOW; CHILDHOOD SEXUAL-ABUSE; FUNCTIONAL NEUROANATOMY; MOOD DISORDERS; MAJOR DEPRESSION; PANIC DISORDER; HUMAN AMYGDALA; ANXIETY; SADNESS; FMRI AB Objective: Separation from loved ones commonly leads to grief reactions. In some individuals, grief can evolve into a major depressive episode. The brain regions involved in grief have not been specifically studied. The authors studied brain activity in women actively grieving a recent romantic relationship breakup. It was hypothesized that while remembering their ex-partner, subjects would have altered brain activity in regions identified in sadness imaging studies: the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex. Method: Nine right-handed women whose romantic relationship ended within the preceding 4 months were studied. Subjects were scanned using blood-oxygen-level-dependent functional magnetic resonance imaging while they alternated between recalling a sad, ruminative thought about their loved one (grief state) and a neutral thought about a different person they knew an equally long time. Results: Acute grief (grief minus neutral state) was associated with increased group activity in posterior brain regions, including the cerebellum, posterior brainstem, and posterior temporoparietal and occipital brain regions. Decreased activity was more prominent anteriorly and on the left and included the anterior brainstem, thalamus, striatum, temporal cortex, insula, and dorsal and ventral anterior cingulate/prefrontal cortex. When a more lenient statistical threshold for regions of interest was used, additional increases were found in the lateral temporal cortex, supragenual anterior cingulate/medial prefrontal cortex, and right inferomedial dorsolateral prefrontal cortex, all of which were adjacent to spatially more prominent decreases. in nearly all brain regions showing brain activity decreases with acute grief, activity decreases were greater in women reporting higher grief levels over the past 2 weeks. Conclusions: During acute grief, subjects showed brain activity changes in the cerebellum, anterior temporal cortex, insula, anterior cingulate, and prefrontal cortex, consistent with the hypothesis. Subjects with greater baseline grief showed greater decreases in all these regions except for the cerebellum. Further imaging studies are needed to understand the relationship between normal sadness, grief, and depression. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Univ Tubingen, Med Ctr, Tubingen, Germany. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Najib, A (reprint author), Krokusweg 21, D-72622 Nurtingen, Germany. EM arif.najib@web.de; lorberjp@musc.edu NR 56 TC 56 Z9 60 U1 7 U2 22 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 DEC PY 2004 VL 161 IS 12 BP 2245 EP 2256 DI 10.1176/appi.ajp.161.12.2245 PG 12 WC Psychiatry SC Psychiatry GA 876NJ UT WOS:000225503500016 PM 15569896 ER PT J AU Schernhammer, ES Colditz, GA AF Schernhammer, ES Colditz, GA TI Suicide rates among physicians: A quantitative and gender assessment (meta-analysis) SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CAUSE-SPECIFIC MORTALITY; MEDICAL DOCTORS; PSYCHIATRIC-ILLNESS; FEMALE PHYSICIANS; PUBLICATION BIAS; 5-YEAR PERIOD; FUNNEL-PLOT; WOMEN; ANESTHESIOLOGISTS; DISTRESS AB Objective: Physicians' suicide rates have repeatedly been reported to be higher than those of the general population or other academics, but uncertainty remains. in this study, physicians' suicide rate ratios were estimated with a metaanalysis and systematic quality assessment of recent studies. Method: Studies of physicians' suicide rates were located in MEDLINE, PsycINFO, AARP Ageline, and the EBM Reviews: Cochrane Database of Systematic Reviews with the terms "physicians," "doctors," "suicide," and "mortality." Studies were included if they were published in or after 1960 and gave estimates of age-standardized suicide rates of physicians and their reference population or reported extractable data on physicians' suicide; 25 studies met the criteria. Reviewers extracted data and scored each study for quality. The studies were tested for heterogeneity and publication bias and were stratified by publication year, follow-up, and study quality. Effect sizes were pooled by using fixed-effects (women) and random-effects (men) models. Results: The aggregate suicide rate ratio for male physicians, compared to the general population, was 1.41, with a 95% confidence interval (Cl) of 1.21-1.65. For female physicians the ratio was 2.27 (95% Cl=1.90-2.73). Visual inspection of funnel plots from tests of publication bias revealed randomness for men but some indication of bias for women, with a relative, nonsignificant lack of studies in the lower right quadrant. Conclusions: Studies on physicians' suicide collectively show modestly (men) to highly (women) elevated suicide rate ratios. Larger studies should help clarify whether female physicians' suicide rate is truly elevated or can be explained by publication bias. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA USA. Dana Faber Harvard Canc Ctr, Program Epidemiol, Boston, MA USA. Kaiser Franz Josef Spital, Med Dept Oncol 3, Vienna, Austria. RP Schernhammer, ES (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM eva.schernhammer@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 59 TC 180 Z9 191 U1 3 U2 21 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 DEC PY 2004 VL 161 IS 12 BP 2295 EP 2302 DI 10.1176/appi.ajp.161.12.2295 PG 8 WC Psychiatry SC Psychiatry GA 876NJ UT WOS:000225503500023 PM 15569903 ER PT J AU Thomas, SB Fine, MJ Ibrahim, SA AF Thomas, SB Fine, MJ Ibrahim, SA TI Health disparities: The importance of culture and health communication SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Minor Hlth, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equit Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Thomas, SB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Minor Hlth, Pittsburgh, PA 15260 USA. NR 0 TC 52 Z9 54 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2050 EP 2050 DI 10.2105/AJPH.94.12.2050 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800006 PM 15612166 ER PT J AU Casas-Zamora, JA Ibrahim, SA AF Casas-Zamora, JA Ibrahim, SA TI Confronting health inequity: The global dimension SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID EQUITY C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. World Hlth Org, European Union, Brussels, Belgium. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11-E,130 A-U, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov NR 37 TC 12 Z9 12 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2055 EP 2058 DI 10.2105/AJPH.94.12.2055 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800009 PM 15569950 ER PT J AU Gurmankin, AD Polsky, D Volpp, KG AF Gurmankin, AD Polsky, D Volpp, KG TI Accounting for apparent "reverse" racial disparities in department of veterans affairs (VA)-based medical care: Influence of out-of-VA care SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PROSTATE-CANCER; OUTCOMES; MORTALITY; SERVICES; LUNG AB Conclusions regarding racial differences in care following a newly elevated prostate-specific antigen (PSA) test at the Department of Veterans Affairs (VA) may differ depending on whether follow-up care outside the VA is considered. Consecutive Philadelphia, Pa, VA patients with newly elevated PSA tests (n = 183) were interviewed 1 year after baseline. Among exclusive VA users, Blacks had higher rates of urology referrals and prostate biopsies compared with Whites. However, these racial differences were attenuated when care obtained outside the VA also was considered. C1 Philadelphia Pittsburgh VA Ctr Hlth Equ Res & Pro, Pittsburgh, PA USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Gurmankin, AD (reprint author), Dana Farber Canc Inst, 44 Binney St,SM 253, Boston, MA 02115 USA. EM adg11@cornell.edu NR 15 TC 12 Z9 12 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2076 EP 2078 DI 10.2105/AJPH.94.12.2076 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800014 PM 15569955 ER PT J AU Kressin, NR Chang, BH Whittle, J Peterson, ED Clark, JA Rosen, AK Orner, M Collins, TC Alley, LG Petersen, LA AF Kressin, NR Chang, BH Whittle, J Peterson, ED Clark, JA Rosen, AK Orner, M Collins, TC Alley, LG Petersen, LA TI Racial differences in cardiac catheterization as a function of patients' beliefs SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CORONARY-REVASCULARIZATION PROCEDURES; INVASIVE CARDIOVASCULAR PROCEDURES; HEALTH-CARE UTILIZATION; MEDICAL-CARE; ETHNIC-DIFFERENCES; VETERANS; ACCESS; ANGIOGRAPHY; RACE/ETHNICITY; ASSOCIATION AB Objectives. We examined racial differences in cardiac catheterization rates and reviewed whether patients' beliefs or other variables were associated with observed disparities. Methods. We did a prospective observational cohort study of 1045 White and African American patients at 5 Veterans Affairs (VA) medical centers whose nuclear imaging studies indicated reversible cardiac ischemia. Results. There were few demographic differences between White and African American patients in our sample. African Americans were less likely than Whites to undergo cardiac catheterization. African Americans were more likely than Whites to indicate a strong reliance on religion and to report racial and social class discrimination and were less likely to indicate a generalized trust in people but did not differ from White patients on numerous other attitudes about health and health care. Neither sociodemographic or clinical characteristics nor patients' beliefs explained the observed disparities, but physicians' assessments of the procedure's importance and patients' likelihood of coronary disease seemed to account for differences not otherwise explained. Conclusions. Patients' preferences are not the likely source of racial disparities in the use of cardiac catheterization among veterans using VA care, but physicians' assessments warrant further attention. C1 VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. Univ Kansas, Med Ctr, Div Gen & Geriatr Med, Kansas City, KS 66103 USA. Kansas City Vet Affairs Med Ctr, Kansas City, MO USA. Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Div Hlth Serv Res, Houston, TX 77030 USA. Atlanta Vet Affairs Med Ctr, Rehabil R&D Ctr, Atlanta, GA USA. Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA. RP Kressin, NR (reprint author), VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA. EM nkressin@bu.edu NR 35 TC 47 Z9 47 U1 2 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2091 EP 2097 DI 10.2105/AJPH.94.12.2091 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800018 PM 15569959 ER PT J AU Woodard, LD Kressin, NR Petersen, LA AF Woodard, LD Kressin, NR Petersen, LA TI Is lipid-lowering therapy underused by African Americans at high risk of coronary heart disease within the VA health care system? SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS; INVASIVE CARDIOVASCULAR PROCEDURES; NUTRITION EXAMINATION SURVEY; SERUM-CHOLESTEROL; ARTERY-DISEASE; BLOOD-PRESSURE; SECONDARY PREVENTION; RACIAL-DIFFERENCES; NATIONAL-HEALTH AB Objectives. We examined whether racial differences exist in cholesterol monitoring, use of lipid-lowering agents, and achievement of guideline-recommended low-density lipoprotein (LDL) levels for secondary prevention of coronary heart disease. Methods. We reviewed charts for 1045 African American and White patients with coronary heart disease at 5 Veterans Affairs (VA) hospitals. Results. Lipid levels were obtained in 67.0% of patients. Whites and African Americans had similar screening rates and mean lipid levels. Among the 544 ideal candidates for therapy, rates of treatment and achievement of target LDL levels were similar. Conclusions. We found no disparities in cholesterol management. This absence of disparities may be the result of VA quality improvement initiatives or prescription coverage through the VA health care system. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Bedford Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02215 USA. RP Woodard, LD (reprint author), Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM lwoodard@bcm.tmc.edu FU BHP HRSA HHS [1 T32 PE 10031-01] NR 44 TC 6 Z9 6 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2112 EP 2117 DI 10.2105/AJPH.94.12.2112 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800021 PM 15569962 ER PT J AU Mustillo, S Krieger, N Gunderson, EP Sidney, S McCreath, H Kiefe, CI AF Mustillo, S Krieger, N Gunderson, EP Sidney, S McCreath, H Kiefe, CI TI Self-reported experiences of racial discrimination and black-white differences in preterm and low-birthweight deliveries: The CARDIA study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BODY-MASS INDEX; BACTERIAL VAGINOSIS; BLOOD-PRESSURE; RISK-FACTORS; PREGNANCY; WOMEN; HEALTH; VALIDITY; STRESS; GAIN AB Objectives. We examined the effects of self-reported experiences of racial discrimination on Black-White differences in preterm (less than 37 weeks gestation) and low-birthweight (less than 2500 g) deliveries. Methods. Using logistic regression models, we analyzed data on 352 births among women enrolled in the Coronary Artery Risk Development in Young Adults Study. Results. Among Black women, 50% of those with preterm deliveries and 61% of those with low-birthweight infants reported having experienced racial discrimination in at least 3 situations; among White women, the corresponding percentages were 5% and 0%. The unadjusted odds ratio for preterm delivery among Black versus White women was 2.54 (95% confidence interval [Cl] = 1.33, 4.85), but this value decreased to 1.88 (95% Cl = 0.85, 4.12) after adjustment for experiences of racial discrimination and to 1.11 (95% Cl = 0.51, 2.41) after additional adjustment for alcohol and tobacco use, depression, education, and income. The corresponding odds ratios for low birthweight were 4.24 (95% Cl = 1.31, 13.67), 2.11 (95% Cl = 0.75, 5.93), and 2.43 (95% Cl = 0.79, 7.42). Conclusions. Self-reported experiences of racial discrimination were associated with preterm and low-birthweight deliveries, and such experiences may contribute to Black-White disparities in perinatal outcomes. C1 Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Kaiser Permanente, Med Care Program, Div Res, Oakland, CA USA. Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Box 3454, Durham, NC 27710 USA. EM smustillo@psych.duhs.duke.edu FU NHLBI NIH HHS [N01HC48049, N01 HC-95095, N01 HC048050, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01HC48047, N01HC48048, N01HC48050, N01HC95095]; NIDDK NIH HHS [K01 DK059944, K01 DK059944-03] NR 52 TC 156 Z9 157 U1 3 U2 12 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2125 EP 2131 DI 10.2105/AJPH.94.12.2125 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800023 PM 15569964 ER PT J AU Acevedo-Garcia, D Barbeau, E Bishop, JA Pan, J Emmons, KM AF Acevedo-Garcia, D Barbeau, E Bishop, JA Pan, J Emmons, KM TI Undoing an epidemiological paradox: The tobacco industry's targeting of US immigrants SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID LOW-BIRTH-WEIGHT; SMOKING INITIATION; RISK-FACTOR; ACCULTURATION; AMERICAN; HEALTH; WOMEN; PERSPECTIVE; PREVALENCE; DEPOSITORY AB Objectives. We sought to ascertain whether the tobacco industry has conceptualized the US immigrant population as a separate market. Methods. We conducted a content analysis of major tobacco industry documents. Results. The tobacco industry has engaged in 3 distinct marketing strategies aimed at US immigrants: geographically based marketing directed toward immigrant communities, segmentation based on immigrants' assimilation status, and coordinated marketing focusing on US immigrant groups and their countries of origin. Conclusions. Public health researchers should investigate further the tobacco industry's characterization of the assimilated and non-assimilated immigrant markets, and its specific strategies for targeting these groups, in order to develop informed national and international tobacco control countermarketing strategies designed to protect immigrant populations and their countries of origin. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Tufts Univ, Community Hlth Program, Medford, MA 02155 USA. RP Acevedo-Garcia, D (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave,7th Floor, Boston, MA 02115 USA. EM dacevedo@hsph.harvard.edu NR 70 TC 21 Z9 21 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2004 VL 94 IS 12 BP 2188 EP 2193 DI 10.2105/AJPH.94.12.2188 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 877IF UT WOS:000225560800031 PM 15569972 ER PT J AU DeFrate, LE Gill, TJ Li, G AF DeFrate, LE Gill, TJ Li, G TI In vivo function of the posterior cruciate ligament during weightbearing knee flexion SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE posterior cruciate ligament (PCL); in vivo knee biomechanics; posterior cruciate ligament kinematics; imaging; magnetic resonance imaging (MRI) ID SIMULATED MUSCLE LOADS; BIOMECHANICAL CONSEQUENCES; RECONSTRUCTED KNEE; GRAFT PLACEMENT; SITU FORCES; 2 BUNDLES; JOINT; VITRO; KINEMATICS; INJURIES AB Background: Current knowledge of posterior cruciate ligament function is mainly based on in vitro cadaveric studies. There are few studies on the in vivo function of the posterior cruciate ligament. The objective of the study was to quantify the multidimensional deformation of the posterior cruciate ligament. Hypothesis: During in vivo weightbearing flexion, the posterior cruciate ligament undergoes complex 3-dimensional deformations, including elongation, twist, and changes in orientation. Study Design: In vivo biomechanical study. Methods: Magnetic resonance images of 5 human knees were used to create 3-dimensional computer models of each subject's knee, including the insertion areas of the posterior cruciate ligament. Orthogonal fluoroscopic images of each subject's knee were acquired as a quasi-static lunge was performed. The images and computer models were used to reproduce the in vivo motion of the knee. The relative motion of the femoral and tibial insertions was described in terms of elongation, twist, elevation (the angle between the tibial plateau and posterior cruciate ligament, measured in the sagittal plane), and deviation (mediolateral orientation, measured in plane of tibial plateau). Results: The length of the posterior cruciate ligament increased significantly with increasing flexion. It twisted almost 801 as the knee flexed from 0degrees to 90degrees. The elevation angle remained relatively constant at 50degrees. The deviation angle was medially oriented by 20degrees at full extension, then decreased to approximately 10degrees at 30degrees through 90degrees of flexion. Conclusion: The posterior cruciate ligament undergoes a complex twisting motion as it elongates with flexion. Clinical Relevance: During reconstruction, the tunnels and graft may need to be placed such that the multidimensional deformation of the intact posterior cruciate ligament is reproduced. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bioengn Lab,Dept Orthopaed Surg, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 31 TC 35 Z9 42 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD DEC PY 2004 VL 32 IS 8 BP 1923 EP 1928 DI 10.1177/0363546504264896 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 874WJ UT WOS:000225380900018 PM 15572322 ER PT J AU Lin, PH Bush, RL Yao, QZ Lam, R Paladugu, R Zhou, W Chen, CY Lumsden, AB AF Lin, PH Bush, RL Yao, QZ Lam, R Paladugu, R Zhou, W Chen, CY Lumsden, AB TI Abdominal aortic surgery in patients with human immunodeficiency virus infection SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Southwestern Surgical Congress CY APR 18-21, 2004 CL Monterey, CA DE human immunodeficiency virus; aortic bypass; aortoiliac occlusive disease; abdominal aortic aneurysm; complications ID QUALITY-OF-LIFE; HIV-INFECTION; HEMODIALYSIS ACCESS; SERUM-ALBUMIN; COMPLICATIONS; DISEASE; WOMEN; AIDS; SURVIVAL; COUNTS AB Purpose: Human immunodeficiency virus (HIV) infection is known to cause acquired immune deficiency syndrome, which has been associated with a wide array of cardiovascular pathologies. This report examined the clinical outcome of patients infected with HIV who underwent abdominal aortic reconstruction for aneurysm or occlusive disease. Methods: Hospital and clinic records of all patients with HIV infection who underwent an abdominal aortic operation were reviewed during an 11-year period. Relevant risk factors and clinical variables were assessed for surgical outcome. Results: Forty-eight HIV patients (mean age 54 +/- 13 years) were identified who underwent abdominal aortic bypass grafting during the study period. Indications for aortic operation included aneurysm (n = 20) and aortoiliac occlusive disease (n = 28). All patients underwent successful aortic reconstructions without intraoperative mortality. Postoperative complications and in-hospital mortality occurred in 16 patients (33%) and 7 patients (15%), respectively. The mean follow-up period was 41 months. Life-table survival rates in aneurysm and occlusive patients at 60 months were 43.2% +/- 5.3% and 46.3% +/- 7.4% (not significant), respectively. Multivariate analysis showed that low CD4 lymphocyte counts (<200/muL, P- <0.05) and hypoalbuminemia (<3.5 g/dL, P <0.05) were risk factors for postoperative complications. Conclusion: Perioperative morbidity and mortality rates are high in HIV patients undergoing an abdominal aortic operation. Low CD4 lymphocyte counts and hypoalbumine'mia are associated with poor clinical outcomes in HIV patients undergoing abdominal aortic reconstruction. (C) 2004 Excerpta Medica Inc. All rights reserved. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Methodist Hosp, Houston VAMC, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 35 TC 24 Z9 26 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2004 VL 188 IS 6 BP 690 EP 696 DI 10.1016/j.amjsurg.2004.08.054 PG 7 WC Surgery SC Surgery GA 885UW UT WOS:000226183600020 PM 15619485 ER PT J AU Watts, K Lin, PH Bush, RL Awad, S McCoy, SA Felkai, D Zhou, W Nguyen, L Guerrero, MA Shenaq, SA Lumsden, AB AF Watts, K Lin, PH Bush, RL Awad, S McCoy, SA Felkai, D Zhou, W Nguyen, L Guerrero, MA Shenaq, SA Lumsden, AB TI The impact of anesthetic modality on the outcome of carotid endarterectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Southwestern Surgical Congress CY APR 18-21, 2004 CL Monterey, CA DE carotid endarterectomy; local anesthesia; complications ID GENERAL-ANESTHESIA; LOCAL-ANESTHESIA; COMPLICATIONS; INSUFFICIENCY; OPERATIONS; ISCHEMIA; SURGERY AB Background: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with high-grade carotid artery stenosis. This study evaluates the clinical outcome of CEA performed under local anesthesia (LA) versus general anesthesia (GA). Methods: Clinical variables and treatment outcomes were analyzed in 548 CEAs performed under either LA or GA during a 30-month period. Factors associated with morbidity were also analyzed. Results: A total of 263 CEAs under LA and 285 CEA under GA were analyzed. The LA group was associated with a lower incidence of shunt placement, operative time, and perioperative hemodynamic instability compared to the. GA group. No differences in neurologic complications or mortality were found between the 2 groups. Hyperlipidemia was a risk factor for postoperative morbidity in both the LA and GA groups, while age greater than 75 years was associated with increased overall morbidity in the GA group but not the LA group. Conclusions: This study demonstrates that increased age is associated with increased morbidity in CEA under GA, while hyperlipidemia is associated with increased morbidity in CEA regardless of the anesthetic choice. (C) 2004 Excerpta Medica Inc. All rights reserved. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Methodist Hosp, Houston VAMC, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, 2002 Holcomb Blvd 112, Houston, TX 77030 USA. EM plin@bcm.tmc.edu NR 25 TC 24 Z9 26 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2004 VL 188 IS 6 BP 741 EP 746 DI 10.1016/j.amjsurg.2004.08.048 PG 6 WC Surgery SC Surgery GA 885UW UT WOS:000226183600036 PM 15619493 ER PT J AU Weigelt, J Kaafarani, HMA Itani, KMF Swanson, RN AF Weigelt, J Kaafarani, HMA Itani, KMF Swanson, RN TI Linezolid eradicates MRSA better than vancomycin from surgical-site infections SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Southwestern Surgical Congress CY APR 18-21, 2004 CL Monterey, CA DE Staphylococcus aureus; gram-positive bacteria; surgical wound infection; linezolid; vancomycin ID SOFT-TISSUE INFECTIONS; ANTIMICROBIAL SUSCEPTIBILITY PATTERNS; RESISTANT STAPHYLOCOCCUS-AUREUS; PROGRAM UNITED-STATES; METHICILLIN-RESISTANT; BACTEREMIA; MORTALITY; SKIN; CANADA AB Background: The purpose of this analysis was to compare the efficacy of linezolid versus vancomycin in patients with suspected or proven gram-positive methicillin-resistant Staphylococcus aureus (MRSA) surgical-site infections. Methods: An open-label, randomized, comparator-controlled, multicenter, multinational study was conducted in hospitalized patients. Patients were randomized 1: 1 to receive linezolid 600 mg (intravenous [IV] or oral) every 12 hours (n = 66) or vancomycin I g every 12 hours IV (n = 69) for 7 to 21 days. Patients were assessed at the test-of-cure (TOC) visit, 7 days after completing therapy. Results: Clinical success at TOC was documented in similar proportions of patients treated with linezolid or vancomycin. Of those with MRSA isolated, significantly more patients who received linezolid compared with those who received vancomycin were microbiologically cured (87% vs 48%, respectively; 95% confidence interval 16.51 to 60.27; P = 0.0022. Conclusion: Intravenous or oral linezolid was well tolerated and superior to vancomycin in treating patients with MRSA-infected surgical-site infections. (C) 2004 Excerpta Medica Inc. All rights reserved. C1 Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Pfizer Inc, New York, NY USA. RP Weigelt, J (reprint author), Med Coll Wisconsin, Dept Surg, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM jweigelt@mail.mcw.edu NR 25 TC 94 Z9 106 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2004 VL 188 IS 6 BP 760 EP 765 DI 10.1016/j.amsjurg.2004.08.045 PG 6 WC Surgery SC Surgery GA 885UW UT WOS:000226183600041 PM 15619496 ER PT J AU Weeratunge, CN Roldan, J Anstead, GM AF Weeratunge, CN Roldan, J Anstead, GM TI Jaccoud arthropathy: A rarity in the spectrum of HIV-associated arthropathy SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Jaccoud arthropathy; AIDS; HIV-associated arthropathy ID ACQUIRED IMMUNODEFICIENCY; RHEUMATIC MANIFESTATIONS; REITERS-SYNDROME; ARTHRITIS; INFECTION AB In studies comparing HIV-infected patients with HIV-negative patients, rheumatic manifestations, including reactive arthritis, psoriatic arthritis, myalgia, tendinitis, fibromyalgia, necrotizing vasculitis, polymyositis, Sjogren syndrome, were shown to occur more frequently in the HIV-positive group. Uncommon clinical features and the demonstration of HIV antigens in the synovial membranes suggest a direct role of HIV in the pathogenesis of HIV-associated rheumatic disease. Jaccoud arthropathy is a nonerosive deforming arthropathy reported to occur in cases of chronic rheumatic fever and systemic lupus erythematosus. Only two cases of HIV-associated Jaccoud arthropathy has been reported in the literature thus far, both in patients with features of reactive arthritis. We report a case of HIV-associated Jaccoud arthropathy in a patient without features of reactive arthropathy. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Clin Immunol & Rheumatol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Weeratunge, CN (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 cnamalw@hotmail.com NR 15 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 2004 VL 328 IS 6 BP 351 EP 353 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 880SD UT WOS:000225808600008 PM 15599332 ER PT J AU Duvivier-Kali, VF Omer, A Lopez-Avalos, MD O'Neil, JJ Weir, GC AF Duvivier-Kali, VF Omer, A Lopez-Avalos, MD O'Neil, JJ Weir, GC TI Survival of microencapsulated adult pig islets in mice in spite of an antibody response SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE islets; transplantation; pig; encapsulation; alginate; immunobarrier; rat ID PORCINE ISLETS; CELL CLUSTERS; DIABETIC MICE; NUDE-MICE; ALGINATE MICROCAPSULES; BIOARTIFICIAL PANCREAS; IN-VITRO; TRANSPLANTATION; XENOTRANSPLANTATION; IMMUNOSUPPRESSION AB The aim of this study was to assess the capacity of simple alginate capsules to protect adult pig islets in a model of xenotransplantation. Adult pig islets were microencapsulated in alginate, with either single alginate coats (SAC) or double alginate coats (DAC), and transplanted into the streptozotocin-induced diabetic B6AF1 mice. Normalization of glucose levels was associated with an improvement of the glucose clearance during intravenous glucose tolerance tests. After explantation, all mice became hyperglycemic, demonstrating the efficacy of the encapsulated pig islets. Explanted capsules were mainly free of fibrotic reaction and encapsulated islets were still functional, responding to glucose stimulation with a 10-fold increase in insulin secretion. However, a significant decrease in the insulin content and insulin responses to glucose was observed for encapsulated islets explanted from hyperglycemic mice. An immune response of both IgG and IgM subtypes was detectable after transplantation. Interestingly, there were more newly formed antibodies in the serum of mice transplanted with SAC capsules than in the serum of mice transplanted with DAC capsules. In conclusion, alginate capsules can prolong the survival of adult pig islets transplanted into diabetic mice for up to 190 days, even in the presence of an antibody response. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. Sanofi Synthelabo, Diabet & Obes Unit, Rueil Malmaison, France. Univ Malaga, Dept Biol Celular Genet & Fisiol, E-29071 Malaga, Spain. Johnson & Johnson Consumer Prod Inc, Lifescan Inc, Skillman, NJ 08558 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. EM Gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [DK 50657, P30 DK36836-16, DK53087] NR 44 TC 39 Z9 40 U1 1 U2 6 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2004 VL 4 IS 12 BP 1991 EP 2000 DI 10.1111/j.1600-6143.2004.00628.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 876HM UT WOS:000225487400011 PM 15575901 ER PT J AU Graves, MC Fiala, M Dinglasan, LAV Liu, NQ Sayre, J Chiappelli, F van Kooten, C Vinters, HV AF Graves, MC Fiala, M Dinglasan, LAV Liu, NQ Sayre, J Chiappelli, F van Kooten, C Vinters, HV TI Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article DE immunopathogenesis of ALS; innate immunity; adaptive immunity; inflammation; mast cells ID TRANSGENIC MOUSE MODEL; PROTECTS MOTOR-NEURONS; UP-REGULATION; SUPEROXIDE-DISMUTASE; ALZHEIMERS-DISEASE; TNF-ALPHA; CYCLOOXYGENASE-2; ALS; CD40; INHIBITION AB Recent studies have shown inflammatory markers in affected neural tissues of amyotrophic lateral sclerosis (ALS) patients. We examined immunocytochemically spinal cord tissues of six patients with ALS, two with corticospinal tract degeneration secondary to cerebral infarcts and three control subjects without neuropathologic abnormalities. ALS spinal cords had dense macrophage infiltration ( one log greater than control spinal cords) involving the white and gray matter, with heaviest infiltration of lateral and ventral columns and, in one patient, prefrontal gyrus and the occipital lobes of the brain. Macrophages in ALS spinal cord showed strong expression of cyclooxygenase-2 (COX-2) ( one log greater than control tissues) and inducible nitric oxide synthase. In the gray matter, macrophages surrounded and appeared to phagocytize neurons (NeuN-positive) that appeared to be dying. Vessels showed damage to the tight junction protein ZO-1 in relation to perivascular CD40 receptor-positive macrophages and CD40 ligand-positive T lymphocytes. ALS spinal cords, but not control cords, were sparsely infiltrated with mast cells. In control cases with corticospinal tract degeneration following hemispheric cerebral infarction, macrophage infiltration of the white matter was COX-2-negative and restricted to lateral and anterior corticospinal tracts. Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Greater Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90024 USA. Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med Neuropathol, Los Angeles, CA USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 63-090, Los Angeles, CA 90095 USA. EM fiala@ucla.edu FU NIA NIH HHS [P50 AG16570] NR 37 TC 83 Z9 83 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PD DEC PY 2004 VL 5 IS 4 BP 213 EP 219 DI 10.1080/14660820410020286 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 881ON UT WOS:000225876900004 PM 15799549 ER PT J AU Goto, T Hanne, P Ishiguro, Y Ichinose, F Niimi, Y Morita, S AF Goto, T Hanne, P Ishiguro, Y Ichinose, F Niimi, Y Morita, S TI Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia SO ANAESTHESIA LA English DT Article DE anaesthetics, inhalational, inert gases; cardiac function; transoesophageal echocardiography ID CARDIAC-FUNCTION; ISOFLURANE; HEMODYNAMICS; SEVOFLURANE; COMBINATION; METABOLISM; HALOTHANE; CURRENTS; KINETICS; HEART AB Xenon anaesthesia appears to have minimal haemodynamic effects. The purpose of this randomised prospective study was to compare the cardiovascular effects of xenon and nitrous oxide in patients with known ischaemic heart disease. In 20 patients who were due to undergo coronary artery bypass graft surgery, 30 min following induction of anaesthesia with fentanyl 30 mug.kg(-1) and midazolam 0.1 mg.kg(-1) but prior to the start of surgery, xenon or nitrous oxide 60% was administered for 15 min. The results showed that xenon caused a minimal decrease in the mean arterial pressure (from 81 (7) to 75 (8) mmHg, mean (SD)), but did not affect the systolic function of the left ventricle, as demonstrated by unchanged left ventricular stroke work index (LVSWI) and the fractional area change of the left ventricle (FAC) derived from transoesophageal echocardiography (TOE). However, in contrast, nitrous oxide was found to decrease the mean arterial pressure (from 81 (8) to 69 (7) mmHg), the LVSWI, and the FAC. The cardiac index, central venous and pulmonary artery occlusion pressures, systemic and pulmonary vascular resistances, and the TOE-derived E/A ratio through the mitral valve were unchanged by xenon or nitrous oxide. We conclude that xenon provides improved haemodynamic stability compared with nitrous oxide, conserving the left ventricular systolic function. C1 Teikyo Univ, Sch Med, Dept Anaesthesia & Crit Care, Itabashi Ku, Tokyo 1738605, Japan. Univ Hosp Schleswig Holstein, Dept Anaesthesiol & Intens Care Med, D-24105 Kiel, Germany. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Teikyo Univ, Ichihara Hosp, Ichihara, Chiba 2990111, Japan. RP Goto, T (reprint author), Teikyo Univ, Sch Med, Dept Anaesthesia & Crit Care, Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan. EM takigoto@med.teikyo-u.ac.jp NR 23 TC 23 Z9 31 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD DEC PY 2004 VL 59 IS 12 BP 1178 EP 1183 DI 10.1111/j.1365-2044.2004.03900.x PG 6 WC Anesthesiology SC Anesthesiology GA 872HC UT WOS:000225197300007 PM 15549976 ER PT J AU Cohen, SP Chang, AS Larkin, T Mao, JR AF Cohen, SP Chang, AS Larkin, T Mao, JR TI The intravenous ketamine test: A predictive response tool for oral dextromethorphan treatment in neuropathic pain SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSTHERPETIC NEURALGIA; POSTOPERATIVE PAIN; DIABETIC NEUROPATHY; DORSAL-HORN; RAT; ANTINOCICEPTION; DEXTRORPHAN; LIDOCAINE; EFFICACY; MORPHINE AB TV infusion tests performed to predict subsequent response to oral analgesics are an increasingly popular method used to enhance medical care and conserve resources. Because no infusion test is completely accurate, the potential benefits of these tests Must be weighed against the frustration and waste in resources encountered with false-positive results, and the failure to use a potentially beneficial treatment with false-negative results. In recent years, drugs that act antagonistically at N-methyl-D-aspartate receptors have been shown to be valuable adjuncts in the treatment of pain. To determine the predictive value of small-dose (0.1 mg/kg) IV ketamine on an oral dextromethorphan (DX) treatment regimen, we analyzed the analgesic response to these drugs in 25 patients at 2 tertiary care military treatment facilities, institutions at which DX is not readily accessible. When greater than or equal to50% response for both drugs was used as the outcome measure for success, the positive predictive value of the ketamine test was 64%, the negative predictive value 73%, and the observed agreement 68%. However, when greater than or equal to67% relief with ketamine was used as an outcome measure (as determined by a receiver operating characteristic curve), the positive predictive value was 90%, the negative predictive value 80%, and the observed agreement increased to 84%. Based on these results, we conclude that an IV ketamine test may be useful in predicting response to oral DX. More research is needed to determine the ideal candidates for such a test, and the optimal dose and cutoff value for the response to ketamine. C1 Johns Hopkins Univ, Pain Management Ctr, Sch Med, Dept Anesthesiol, Baltimore, MD 21205 USA. Walter Reed Army Med Ctr, Dept Anesthesiol, Pain Managment Ctr, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Anesthesiol, Washington, DC 20307 USA. Landstuhl Reg Army Med Ctr, Landstuhl, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA USA. RP Cohen, SP (reprint author), Johns Hopkins Univ, Pain Management Ctr, Sch Med, Dept Anesthesiol, 550 N Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen@jhmi.edu NR 27 TC 18 Z9 20 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 DEC PY 2004 VL 99 IS 6 BP 1753 EP 1759 DI 10.1213/01.ANE.0000136953.11583.7B PG 7 WC Anesthesiology SC Anesthesiology GA 874HN UT WOS:000225341600032 PM 15562066 ER PT J AU Lecamwasam, HS Baboolal, HA Dunn, PF AF Lecamwasam, HS Baboolal, HA Dunn, PF TI Acute adrenal insufficiency after large-dose glucocorticoids for spinal cord injury SO ANESTHESIA AND ANALGESIA LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; TIRILAZAD MESYLATE; METHYLPREDNISOLONE AB A 24- to 48-h course of large-dose glucocorticoid therapy is often used in the acute management of spinal cord injury. We describe a patient who developed adrenal insufficiency (AI) after this protocol. Although a definitive causal relationship between the steroids and AI was not established, their temporal association and the exclusion of other possible etiologies led us to postulate that AI was a complication of the steroid protocol. Clinicians should, therefore, consider AI in patients with spinal cord injury receiving glucocorticoids, a population in whom it may otherwise go undiagnosed and untreated. C1 Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Dunn, PF (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, GRB 04-424,55 Fruit St, Boston, MA 02114 USA. EM pdunn@partners.org NR 12 TC 7 Z9 7 U1 0 U2 1 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 DEC PY 2004 VL 99 IS 6 BP 1813 EP 1814 DI 10.1213/01.ANE.0000138058.08094.A4 PG 2 WC Anesthesiology SC Anesthesiology GA 874HN UT WOS:000225341600043 PM 15562077 ER PT J AU De Fosse, L Hodge, SM Makris, N Kennedy, DN Caviness, VS McGrath, L Steele, S Ziegler, DA Herbert, MR Frazier, JA Tager-Flusberg, H Harris, GJ AF De Fosse, L Hodge, SM Makris, N Kennedy, DN Caviness, VS McGrath, L Steele, S Ziegler, DA Herbert, MR Frazier, JA Tager-Flusberg, H Harris, GJ TI Language-association cortex asymmetry in autism and specific language impairment SO ANNALS OF NEUROLOGY LA English DT Article ID AUTOMATED IMAGE REGISTRATION; PLANUM TEMPORALE ASYMMETRY; BRAIN ABNORMALITIES; PARS TRIANGULARIS; MRI ASYMMETRIES; STROKE PATIENTS; CHROMOSOME 7Q; IN-VIVO; SPEECH; DISORDER AB fLanguage deficits are among the core impairments of autism. We previously reported asymmetry reversal of frontal language cortex in boys with autism. Specific language impairment (SLI) and autism share similar language deficits and may share genetic links. This study evaluated asymmetry of frontal language cortex in a new, independent sample of right-handed boys, including a new sample of boys with autism and a group of boys with SLI. The boys with autism were divided into those with language impairment (ALI) and those with normal language ability (ALN). Subjects (right-handed, aged 6.2-13.4 years) included 22 boys with autism (16 ALI and 6 ALN), 9 boys with a history of or present SLI, and 11 normal controls. MRI brain scans were segmented into grey and white matter; then the cerebral cortex was parcellated into 48 gyral-based divisions per hemisphere. Group differences in volumetric asymmetry were predicted a priori in language-related regions in inferior lateral frontal (Broca's area) and posterior superior temporal cortex. Language impaired boys with autism and SLI both had significant reversal of asymmetry in frontal language-related cortex; larger on the right side in both groups of language impaired boys and larger on the left in both unimpaired language groups, strengthening a phenotypic link between ALI and SLI. Thus, we replicated the observation of reversed asymmetry in frontal language cortex reported previously in an independent autism sample, and observed similar reversal in boys with SLI, further strengthening a phenotypic link between SLI and a subgroup of autism. Linguistically unimpaired boys with autism had similar asymmetry compared with the control group, suggesting that Broca's area asymmetry reversal is related more to language impairment than specifically to autism diagnosis. C1 Massachusetts Gen Hosp, Ctr Morphomet Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Child Psychiat Outpatient Clin, Belmont, MA 02178 USA. RP Harris, GJ (reprint author), Zero Emerson Pl 3A, Boston, MA 02114 USA. EM gjharris@partners.org RI Tager-Flusberg, Helen/D-5265-2009; Kennedy, David/H-3627-2012; OI McGrath, Lauren/0000-0001-6928-9656 FU NIDCD NIH HHS [U19/P01 DC03610]; NIMH NIH HHS [K08 MH01573-01] NR 68 TC 141 Z9 143 U1 6 U2 15 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 DEC PY 2004 VL 56 IS 6 BP 757 EP 766 DI 10.1002/ana.20275 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 876NV UT WOS:000225504700002 PM 15478219 ER PT J AU Pagani, O Gelber, S Price, K Zahrieh, D Gelber, R Simoncini, E Castiglione-Gertsch, M Coates, AS Goldhirsch, A Collins, J Thurlimann, B Senn, HJ Holmberg, S Lindtner, J Veronesi, A Cortes-Funes, H Hiltbrunner, A Ditesheim, V Jenatsch, C Egli, G Rabaglio, M Maibach, R Gelber, R Price, K Gelber, S Zahrieh, D Bonetti, M Keshaviah, A Li, S O'Neill, A Regan, M Bernhard, J Hurny, C Wechsler, Y Gusterson, B Viale, G Spataro, V Mallon, E Blacher, L Celano, J Isley, M Hinkle, R Lippert, S Scott, K Rudenstam, CM Wallgren, A Ottosson-Lonn, S Hultborn, R Colldahl-Jadestrom, G Cahlin, E Mattsson, J Holmberg, SB Ruusvik, O Niklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Groot, O Dahlback, LO Salander, H Andersson, C Heideman, M Nissborg, A Wallin, A Claes, G Ramhult, T Svensson, JH Liedberg, P Nilsson, A Havel, G Oestberg, G Persson, S Suurkula, M Matusik, J Goldhirsch, A Colleoni, M Martinelli, G Viale, G Renne, G Mazzarol, G Orlando, L Nole, F Torrisi, R De Pas, T de Braud, F Cinieri, S Peruzzotti, G Peccatori, F Luini, A Orecchia, R Costa, A Zurrida, S Veronesi, P Sacchini, V Galimberti, V Intra, M Veronesi, U Veronesi, A Crivellari, D Monfardini, S Galligioni, E Magri, MD Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Roncadin, M Arcicasa, M Coran, F Morassut, S Ravaioli, A Tassinari, D Oliverio, G Barbanti, F Rinaldi, P Pini, E Drudi, G Murray, E Werner, ID Dent, DM Gudgeon, A McEvoy, E Toop, J Lindtner, J Erzen, D Cufer, T Cervek, J Cerar, O Zakotnik, B Majdic, E Goloub, R Lamovec, J Jancar, J Vrhovec, I Kramberger, M Simoncini, E Marini, G Marpicati, P Braga, M Grigolato, P Lucini, L Cortes-Funes, H Mendiola, D Hornedo, J Colomer, R Mendez, M Vigo, FC Miranda, P Sierra, A Martinez-Tello, F Garzon, A Alonso, S Ferrero, A Vorobiof, D Chasen, M Fotheringham, G de Muelenaere, G Skudowitz, B Mohammed, C Antimi, M Minelli, M Bellini, V Porzio, R Pernazza, E Santeusanio, G Spagnoli, LG Foladore, S Foghin, L Pamich, G Bianchi, C Marino, B Murgia, A Milan, V Lang, I Horvath, Z Szamel, I Lactionov, KP Semiglazov, VF Fey, MF Castiglione-Gertsch, M Dreher, E Schneider, H Aebi, S Buser, K Ludin, J Beck, G Haenel, A Luthi, JM Altermatt, HJ Nandedkar, M Senn, HJ Thurlimann, B Oehlschlegel, C Ries, G Topfer, M Lorenz, U Ehrsam, A Spati, B Vogel, E Cavalli, F Pagani, O Neuenschwander, H Bronz, L Sessa, C Ghielmini, M Rusca, T Rey, P Bernier, J Pedrinis, E Gyr, T Leidi, L Pastorelli, G Goldhirsch, A Herrmann, R Rochlitz, CF Oertli, D Wight, E Moch, H Piguet, D Siegenthaler, P Barrelet, V Baumann, RP Pestalozzi, B Sauter, C Haller, U Huguenin, P Caduff, R Perey, L Leyvraz, S Anani, P Genton, C Gomez, F De Grandi, P Reymond, P Mirimanoff, R Gillet, M Delaloye, JF Diebold-Berger, S Bonnefoi, H Schafer, P Kurtz, J Egli, F Forrer, P Willi, A Steiner, R Allemann, J Ruedi, T Leutenegger, A Dalla Torre, U Schonenberger, A Wernli, M Bargetzi, M Mingrone, W Schmid, P Bartschi, E Beretta, K AF Pagani, O Gelber, S Price, K Zahrieh, D Gelber, R Simoncini, E Castiglione-Gertsch, M Coates, AS Goldhirsch, A Collins, J Thurlimann, B Senn, HJ Holmberg, S Lindtner, J Veronesi, A Cortes-Funes, H Hiltbrunner, A Ditesheim, V Jenatsch, C Egli, G Rabaglio, M Maibach, R Gelber, R Price, K Gelber, S Zahrieh, D Bonetti, M Keshaviah, A Li, S O'Neill, A Regan, M Bernhard, J Hurny, C Wechsler, Y Gusterson, B Viale, G Spataro, V Mallon, E Blacher, L Celano, J Isley, M Hinkle, R Lippert, S Scott, K Rudenstam, CM Wallgren, A Ottosson-Lonn, S Hultborn, R Colldahl-Jadestrom, G Cahlin, E Mattsson, J Holmberg, SB Ruusvik, O Niklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Groot, O Dahlback, LO Salander, H Andersson, C Heideman, M Nissborg, A Wallin, A Claes, G Ramhult, T Svensson, JH Liedberg, P Nilsson, A Havel, G Oestberg, G Persson, S Suurkula, M Matusik, J Goldhirsch, A Colleoni, M Martinelli, G Viale, G Renne, G Mazzarol, G Orlando, L Nole, F Torrisi, R De Pas, T de Braud, F Cinieri, S Peruzzotti, G Peccatori, F Luini, A Orecchia, R Costa, A Zurrida, S Veronesi, P Sacchini, V Galimberti, V Intra, M Veronesi, U Veronesi, A Crivellari, D Monfardini, S Galligioni, E Magri, MD Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Roncadin, M Arcicasa, M Coran, F Morassut, S Ravaioli, A Tassinari, D Oliverio, G Barbanti, F Rinaldi, P Pini, E Drudi, G Murray, E Werner, ID Dent, DM Gudgeon, A McEvoy, E Toop, J Lindtner, J Erzen, D Cufer, T Cervek, J Cerar, O Zakotnik, B Majdic, E Goloub, R Lamovec, J Jancar, J Vrhovec, I Kramberger, M Simoncini, E Marini, G Marpicati, P Braga, M Grigolato, P Lucini, L Cortes-Funes, H Mendiola, D Hornedo, J Colomer, R Mendez, M Vigo, FC Miranda, P Sierra, A Martinez-Tello, F Garzon, A Alonso, S Ferrero, A Vorobiof, D Chasen, M Fotheringham, G de Muelenaere, G Skudowitz, B Mohammed, C Antimi, M Minelli, M Bellini, V Porzio, R Pernazza, E Santeusanio, G Spagnoli, LG Foladore, S Foghin, L Pamich, G Bianchi, C Marino, B Murgia, A Milan, V Lang, I Horvath, Z Szamel, I Lactionov, KP Semiglazov, VF Fey, MF Castiglione-Gertsch, M Dreher, E Schneider, H Aebi, S Buser, K Ludin, J Beck, G Haenel, A Luthi, JM Altermatt, HJ Nandedkar, M Senn, HJ Thurlimann, B Oehlschlegel, C Ries, G Topfer, M Lorenz, U Ehrsam, A Spati, B Vogel, E Cavalli, F Pagani, O Neuenschwander, H Bronz, L Sessa, C Ghielmini, M Rusca, T Rey, P Bernier, J Pedrinis, E Gyr, T Leidi, L Pastorelli, G Goldhirsch, A Herrmann, R Rochlitz, CF Oertli, D Wight, E Moch, H Piguet, D Siegenthaler, P Barrelet, V Baumann, RP Pestalozzi, B Sauter, C Haller, U Huguenin, P Caduff, R Perey, L Leyvraz, S Anani, P Genton, C Gomez, F De Grandi, P Reymond, P Mirimanoff, R Gillet, M Delaloye, JF Diebold-Berger, S Bonnefoi, H Schafer, P Kurtz, J Egli, F Forrer, P Willi, A Steiner, R Allemann, J Ruedi, T Leutenegger, A Dalla Torre, U Schonenberger, A Wernli, M Bargetzi, M Mingrone, W Schmid, P Bartschi, E Beretta, K CA Int Breast Canc Study Grp TI Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93 SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant therapy; early-stage breast cancer; tamoxifen; toremifene ID SURGICAL ADJUVANT BREAST; QUALITY-OF-LIFE; RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; PHASE-III; TRIPHENYLETHYLENE COMPOUND; ANTIESTROGENS TAMOXIFEN; ENDOMETRIAL CANCER; LIPID LEVELS; DNA-ADDUCTS AB Background: Toremifene is a chlorinated derivative of tamoxifen, developed to improve its risk-benefit profile. The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials for peri- and postmenopausal patients with node-positive breast cancer to compare toremifene versus tamoxifen as the endocrine agent and simultaneously investigate a chemotherapy-oriented question. This is the first report of the endocrine comparison after a median follow-up of 5.5 years. Patients and methods: 1035 patients were available for analysis: 75% had estrogen receptor (ER)positive primary tumors, the median number of involved axillary lymph nodes was three and 81% received prior adjuvant chemotherapy. Results: Toremifene and tamoxifen yielded similar disease-free (DFS) and overall survival (OS): 5-year DFS rates of 72% and 69%, respectively [risk ratio (RR)=0.95; 95% confidence interval (Cl)=0.76-1.18]; 5-year OS rates of 85% and 81%, respectively (RR = 1.03; 95% CI = 0.78-1.36). Similar outcomes were observed in the ER-positive cohort. Toxicities were similar in the two treatment groups with very few women (< 1%) experiencing severe thromboembolic or cerebrovascular complications. Quality of life results were also similar. Nine patients developed early stage endometrial cancer (toremifene, six; tamoxifen, three). Conclusions: Toremifene is a valid and safe alternative to tamoxifen in postmenopausal women with endocrine-responsive breast cancer. C1 Osped Beata Vergine, Inst Oncol Svizzera Italiana IOSI, CH-6850 Mendrisio, Switzerland. Dana Farber Canc Inst, Frontier Sci & Technol Res Fdn, IBCSG Stat Ctr, Boston, MA USA. Oncol Med Spedali Civili, Brescia, Italy. IBCSG Coordinating Ctr, Bern, Switzerland. Canc Council Australia, Unley, Australia. Univ Sydney, Sydney, NSW 2006, Australia. European Inst Oncol, Milan, Italy. RP Pagani, O (reprint author), Osped Beata Vergine, Inst Oncol Svizzera Italiana IOSI, CH-6850 Mendrisio, Switzerland. EM opagani@siak.ch RI gusterson, barry/D-3752-2009; Horvath, Zsolt/B-9524-2012; Colomer, Ramon/C-5142-2008 OI Colomer, Ramon/0000-0002-6393-3444 NR 55 TC 56 Z9 61 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 2004 VL 15 IS 12 BP 1749 EP 1759 DI 10.1093/annonc/mdh463 PG 11 WC Oncology SC Oncology GA 877IH UT WOS:000225561100004 ER PT J AU Gaissert, HA Grillo, HC Shadmehr, B Wright, CD Gokhale, M Wain, JC Mathisen, DJ AF Gaissert, HA Grillo, HC Shadmehr, B Wright, CD Gokhale, M Wain, JC Mathisen, DJ TI Long-term survival after resection of primary adenoid cystic and squamous cell carcinoma of the trachea and carina SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 26-28, 2004 CL San Antonio, TX SP Soc Thorac Surg ID TUMORS; EXPERIENCE; TUMOURS; AIRWAY AB Background. Tracheal resection for primary carcinoma may extend survival. We evaluated survival after surgical resection or palliative therapy to identify prognostic factors. Methods. We conducted a retrospective study of patients diagnosed with primary adenoid cystic carcinoma (ACC) or squamous cell carcinoma (SCC) of the trachea between 1962 and 2002. Laryngotracheal, tracheal, or carinal resection was performed when distant metastasis and invasion of adjacent mediastinal structures were absent and tumor length permitted. Radiotherapy was administered after operation (54 Gy), except in superficial tumors, or as palliation (60 Gy). Results. Of 270 patients with ACC or SCC (135 each), 191 (71%) were resected. Seventy-nine were not resected due to tumor length (67%), regional extent (24%), distant metastasis (7%), or other reasons (2%). Overall operative mortality was 7.3% (14/191) and improved each decade from 21% to 3%. Tumor in airway margins was present in 40% (17/191) of resected patients (ACC 59% versus SCC 18%) and lymph node metastasis in 19.4% (37/191). Overall 5- and 10-year survival in resected ACC was 52% and 29% (unresectable 33% and 10%) and in resected SCC 39% and 18% (unresectable 7.3%, and 4.9%). Multivariate analysis of long-term survival found statistically significant associations with complete resection (p < 0.05), negative airway margins (p < 0.05), and adenoid cystic histology (p < 0.001), but not with tumor length, lymph node status, or type of resection. Conclusions. Locoregional, not distant, disease determines resectability in primary tracheal carcinoma. Resection of trachea or carina is associated with long-term survival superior to palliative therapy, particularly for patients with complete resection, negative airway margins, and ACC. (C) 2004 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Policy Anal Inc, Brookline, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org OI shadmehr, mohammad behgam/0000-0002-3303-6750 NR 13 TC 80 Z9 88 U1 4 U2 8 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 DEC PY 2004 VL 78 IS 6 BP 1889 EP 1896 DI 10.1016/j.athoracsur.2004.05.064 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 877HW UT WOS:000225559800001 PM 15560996 ER PT J AU Finegold, SA Molitoris, D Vaisanen, ML Song, YL Liu, CX Bolanos, M AF Finegold, SA Molitoris, D Vaisanen, ML Song, YL Liu, CX Bolanos, M TI In vitro activities of OPT-80 and comparator drugs against intestinal bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GLYCOPEPTIDE RESISTANCE; CLOSTRIDIUM-DIFFICILE; DIARRHEA AB The activities of OPT-80 against 453 intestinal bacteria were compared with those of seven other drugs. OPT-80 showed good activity against most clostridia, staphylococci, and enterococci, but streptococci, aerobic and facultative gram-negative rods, anaerobic gram-negative rods, and Clostridium ramosum were resistant. Poor activity against anaerobic gram-negative rods may maintain colonization resistance. C1 VA Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. RP Finegold, SA (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM sidfinegol@aol.com NR 19 TC 85 Z9 90 U1 0 U2 2 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 DEC PY 2004 VL 48 IS 12 BP 4898 EP 4902 DI 10.1128/AAC.48.12.4898-4902.2004 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 876CW UT WOS:000225474500061 PM 15561877 ER PT J AU Lieberman, J AF Lieberman, J TI RNAi: Towards in vivo therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY OCT 25-28, 2004 CL Washington, DC C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2004 VL 9 IS 6 BP H5 EP H5 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 960TL UT WOS:000231616000163 ER PT J AU Grinspoon, S Kotler, D Allas, S Lussier, B Chapdelaine, A Tellier, JM Domec, MC Vachon, L Abribat, T Falutz, J AF Grinspoon, S Kotler, D Allas, S Lussier, B Chapdelaine, A Tellier, JM Domec, MC Vachon, L Abribat, T Falutz, J TI Effects of a growth hormone releasing factor (GRF) analogue in HIV patients with abdominal fat accumulation: a randomized placebo-controlled trial SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY OCT 25-28, 2004 CL Washington, DC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. St Lukes Roosevelt Hosp, New York, NY USA. Theratechnol Inc, Montreal, PQ, Canada. Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2004 VL 9 IS 6 MA 002 BP L4 EP L4 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 960TL UT WOS:000231616000031 ER PT J AU Kamin, DS Hadigan, C Lehrke, M Lazar, MA Grinspoon, S AF Kamin, DS Hadigan, C Lehrke, M Lazar, MA Grinspoon, S TI Resistin decreases after 3 months of rosiglitazone in HIV-infected patients with lipodystrophy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 6th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY OCT 25-28, 2004 CL Washington, DC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA USA. Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Penn Diabet Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2004 VL 9 IS 6 BP L54 EP L55 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 960TL UT WOS:000231616000122 ER PT J AU Jacobson, CC Resneck, JS Kimball, AB AF Jacobson, CC Resneck, JS Kimball, AB TI Generational differences in practice patterns of dermatologists in the United States - Implications for workforce planning SO ARCHIVES OF DERMATOLOGY LA English DT Article ID GENERAL-PRACTITIONERS; FEMALE PHYSICIANS; WOMEN PHYSICIANS; SEX-DIFFERENCES; GENDER; WORK; TRENDS; CARE; MEN; PRODUCTIVITY AB Objective: To examine the effect of age and other demographic factors on dermatologists' practice characteristics. Design: Anonymous practice profile survey Participants: Dermatologist members of the American Academy of Dermatology Association. Main Outcome Measures: Analyzed survey questions included information about legal practice entity, geographic area served, weekly patient care hours, patients seen per hour, and scope of patient care activities. Results: Of 4090 surveys sent, 1425 (35%) were returned. As the age of the cohorts increased, the percentage practicing in solo practices increased (range, 21%-39%), as did the percentage serving urban areas (range, 31%-46%). Measures of physician productivity increased in the older age cohorts; however, age was not a significant factor after controlling for other variables. More patient-hours per week were associated with male sex (P<.001), solo practices (P<.001), and non-urban-based practices (P=.04), whereas a greater number of patients per hour was associated with non-rural-based practices (P=.02) and male sex (P=.03). As the cohorts progressed in age, more time was spent practicing medical dermatology. The number of hours spent practicing cosmetic dermatology peaked in the 41- to 50-year-old cohort (P=.03). Conclusions: Practice patterns differ significantly among dermatologists of different ages. As the current cohorts age and new dermatologists emerge from training, changes in scope of practice and generational differences in productivity are likely to cause a contraction in the effective supply of dermatologists, which has important implications for dermatology workforce planning. C1 Stanford Univ, Sch Med, Dept Dermatol, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Sch Med, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dermatol Clin Trials Unit, 221 Longwood Ave, Boston, MA 02115 USA. NR 41 TC 29 Z9 29 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2004 VL 140 IS 12 BP 1477 EP 1482 DI 10.1001/archderm.140.12.1477 PG 6 WC Dermatology SC Dermatology GA 879FL UT WOS:000225701700009 PM 15611425 ER PT J AU Nogueira, RG Traynor, B AF Nogueira, RG Traynor, B TI The neurology of varicella-zoster virus - A historical perspective SO ARCHIVES OF NEUROLOGY LA English DT Article ID HERPES-ZOSTER; POSTHERPETIC NEURALGIA; DNA; THERAPY; PAIN AB Varicella-zoster virus (VZV) causes 2 distinctive syndromes: varicella (chickenpox), the primary infection, which is usually a benign epidemical illness from childhood that manifests as a generalized pruritic rash, and herpes zoster (shingles), which results from the reactivation of latent VZV within the sensory ganglia and typically manifests as a painful dermatomal eruption. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Blake 1291,55 Fruit St, Boston, MA 02114 USA. EM rnogueira@partners.org RI Traynor, Bryan/G-5690-2010 NR 38 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2004 VL 61 IS 12 BP 1974 EP 1977 DI 10.1001/archneur.61.12.1974 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 878OM UT WOS:000225656100026 PM 15596626 ER PT J AU Chen, TC Walton, DS Bhatia, LS AF Chen, TC Walton, DS Bhatia, LS TI Aphakic glaucoma after congenital cataract surgery SO ARCHIVES OF OPHTHALMOLOGY 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 INFANTILE CATARACTS; LENS IMPLANTATION; CHILDREN; COMPLICATIONS; LENSECTOMY; VITRECTOMY; EXTRACTION AB Objective: To describe the largest series of patients who developed aphakic glaucoma after lensectomy for congenital cataracts. Methods: A retrospective review was performed of all patients seen by a pediatric glaucoma specialist between October 1, 1970, and November 30, 2002. Patients with intraocular pressures greater than 25 mm Hg after lensectomy were studied. Patients with either conditions independently associated with glaucoma or any signs of glaucoma before lensectomy were excluded. Results: We studied 170 eyes of 117 patients. The mean +/-SD follow-up period was 8.6+/-7.6 years. The most common cataract types were complete (40.8%) and nuclear (22.5%). For the lensectomies, 103 eyes underwent modern vitrectomy techniques, and 10 underwent older techniques. Lensectomies were performed in 80.6% of eyes before age 1 year. Onset of glaucoma after lensectomy was by 1 year in 37.1% of eyes, by 6 years in 75.9%, and by 33 years in 100%. Of eyes that had gonioscopy, 93.9% had open angles. Glaucoma surgery was needed in 57.1% of eyes. The median final visual acuity was 20/400. Conclusions: Most cases of aphakic glaucoma are of the open-angle type. Various risk factors are suggested, and the prognosis is guarded. Lifelong follow-up is needed to screen for glaucoma. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Glaucoma Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chen, TC (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu NR 35 TC 53 Z9 58 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2004 VL 122 IS 12 BP 1819 EP 1825 DI 10.1001/archopht.122.12.1819 PG 7 WC Ophthalmology SC Ophthalmology GA 877DW UT WOS:000225549000010 PM 15596586 ER PT J AU Schwartz, DL Rajendran, J Yueh, B Coltrera, MD LeBlanc, M Eary, J Krohn, K AF Schwartz, DL Rajendran, J Yueh, B Coltrera, MD LeBlanc, M Eary, J Krohn, K TI FDG-PET prediction of head and neck squamous cell cancer outcomes SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; BREAST-CANCER; GLUCOSE-METABOLISM; F-18-FDG PET; CARCINOMA; RADIOTHERAPY; THERAPY; IMPACT; TUMORS AB Objective: To confirm that high pretreatment uptake of 2-deoxy-2[F-18]fluoro-D-glucose (FDG) detected by positron emission tomography (PET) measured at the primary head and neck squamous cell carcinoma (HNSCC) and at metastatic nodal disease predicts poor outcomes for HNSCC. Design and Patients: We enrolled 63 consecutive patients with a histological diagnosis of HNSCC (including tumors of the oral cavity, oropharynx, larynx, and hypopharynx) from September 2000 through June 2003, into a prospective institutional imaging trial. Fifty-four patients (86%) underwent a baseline FDG-PET scan before curative treatment and were eligible for analysis. Results: A primary tumor standardized uptake value (SUV) of greater than 9.0 predicted inferior local recurrence-free survival (P = .02) and disease-free survival (P = .03). Nodal SUV dichotomized according to the cohort median of 6.1 did not predict for either disease outcome (P = .71 and P = .98, respectively). On proportional hazards analysis, local recurrence and disease event hazard ratios for a primary tumor SUV of 9.0 or greater remained significant or at borderline significance when adjusted for nodal SUV or other clinical covariates. Conclusions: Our findings support an association between baseline primary tumor FDG SUV and HNSCC outcomes. In contrast, nodal FDG SUV was not predictive. Primary tumor FDG SUV is a promising prognostic factor and may establish the need for intensified locoregional therapy in individual patients. Multi-institutional imaging trials and further characterization of the biology responsible for elevated FDG uptake in HNSCC will be necessary to confirm the prognostic utility of FDG-labeled PET. C1 Univ Washington, Radiat Oncol Serv, Seattle, WA 98195 USA. Univ Washington, Surg & Perioperat Care Serv, Seattle, WA 98195 USA. Univ Washington, Hlth Serv Res & Dev Serv, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Schwartz, DL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd,Unit 97, Houston, TX 77030 USA. EM docdls@mdanderson.org OI Yueh, Bevan/0000-0003-1380-1053 FU NCI NIH HHS [CA42045] NR 30 TC 112 Z9 115 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD DEC PY 2004 VL 130 IS 12 BP 1361 EP 1367 DI 10.1001/archotol.130.12.1361 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 877WT UT WOS:000225606400001 PM 15611393 ER PT J AU Laposata, ME Laposata, M Van Cott, EM Buchner, DS Kashalo, MS Dighe, AS AF Laposata, ME Laposata, M Van Cott, EM Buchner, DS Kashalo, MS Dighe, AS TI Physician survey of a laboratory medicine interpretive service and evaluation of the influence of interpretations on laboratory test ordering SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CURBSIDE CONSULTATIONS; INFORMATION NEEDS; QUALITY; CARE; MET AB Context.-Complex coagulation test panels ordered by clinicians are typically reported to clinicians without a patient-specific interpretive paragraph. Objectives.-To survey clinicians regarding pathologist-generated interpretations of complex laboratory testing panels and to assess the- ability of the interpretations to educate test orderers. Design.-Surveys were conducted of physicians ordering complex coagulation laboratory testing that included narrative interpretation. Evaluation of order requisitions was performed to assess the interpretation's influence on ordering practices. Setting.-Physicians ordering coagulation testing at a large academic medical center hospital in Boston, Mass, and physicians from outside hospitals using the academic medical center as a reference laboratory for coagulation testing. Outcome Measures.-Physician surveys and evaluation of laboratory requisition slips. Results.-In nearly 80% of responses, the ordering clinicians perceived that the interpretive comments saved them time and improved the diagnostic process. Moreover, the interpretations were perceived by ordering clinicians to help prevent a misdiagnosis or otherwise impact the differential diagnosis in approximately 70% of responses. In addition, interpretations appeared to be able to train the ordering clinicians as to the standard ordering practices. Conclusions.-The results demonstrate physician satisfaction with an innovative information delivery approach that provides laboratory diagnostic interpretation and testordering education to clinicians in the context of their daily workflow. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laposata, ME (reprint author), Massachusetts Gen Hosp, 55 Fuit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 19 TC 53 Z9 53 U1 0 U2 4 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 DEC PY 2004 VL 128 IS 12 BP 1424 EP 1427 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 879LU UT WOS:000225720100024 PM 15578888 ER PT J AU Choi, HK AF Choi, HK TI Diet and rheumatoid arthritis: Red meat and beyond SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID MEDITERRANEAN DIET; FISH CONSUMPTION; MORTALITY; DISEASE; WOMEN; OIL C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org NR 17 TC 4 Z9 4 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 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 3745 EP 3747 DI 10.1002/art.20732 PG 3 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200002 PM 15593227 ER PT J AU Gomoll, AH Katz, JN Warner, JJP Millett, PJ AF Gomoll, AH Katz, JN Warner, JJP Millett, PJ TI Rotator cuff disorders - Recognition and management among patients with shoulder pain SO ARTHRITIS AND RHEUMATISM LA English DT Review ID SUBACROMIAL IMPINGEMENT SYNDROME; FULL-THICKNESS TEARS; DOUBLE-BLIND; NONOPERATIVE MANAGEMENT; PRIMARY-CARE; CORTICOSTEROID INJECTIONS; ASYMPTOMATIC SHOULDERS; ARTHROSCOPIC FINDINGS; OPERATIVE TREATMENT; GENERAL-PRACTICE C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Millett, PJ (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM pmillett@partners.org FU NIAMS NIH HHS [K24-AR-02123, P60-AR-47782] NR 81 TC 39 Z9 42 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 3751 EP 3761 DI 10.1002/art.20668 PG 11 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200004 PM 15593187 ER PT J AU Lieberman, ES Collier, DS Choi, HK AF Lieberman, ES Collier, DS Choi, HK TI Diagnostic utility of anti-cyclic citrullinated peptide antibodies (anti-CCP) for rheumatoid arthritis - A meta-analysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 DEC PY 2004 VL 50 IS 12 BP 4085 EP 4085 PG 1 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200066 ER PT J AU Goldstein, JL Eisen, G Lewis, B Gralnek, L Zlotnick, S AF Goldstein, JL Eisen, G Lewis, B Gralnek, L Zlotnick, S TI Small bowel mucosal breaks associated with ibuprofen plus omeprazole, celecoxib, or placebo in healthy subjects as determined by video capsule endoscopy: Results from a multicenter, double-blind, randomized, controlled trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 Univ Illinois, Chicago, IL USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Pfizer Inc, New York, NY USA. NR 0 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 DEC PY 2004 VL 50 IS 12 BP 4099 EP 4099 PG 1 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200104 ER PT J AU Lieberman, ES Jick, SS Rahman, MU Choi, HK AF Lieberman, ES Jick, SS Rahman, MU Choi, HK TI Corticosteroids, anti-rheumatic drugs, and risk of tuberculosis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 68th Annual Scientific Meeting of the American-College-of-Rheumatology CY OCT 16-21, 2004 CL San Antonio, TX SP Amer Coll Rheumatol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Boston Collaborat Drug Surveillance Program, Lexington, MA USA. Centocor Inc, Malvern, PA 19355 USA. NR 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2004 VL 50 IS 12 BP 4101 EP 4102 PG 2 WC Rheumatology SC Rheumatology GA 879WP UT WOS:000225750200111 ER PT J AU Baker, SR Victor, JB Chambers, AL Halverson, CF AF Baker, SR Victor, JB Chambers, AL Halverson, CF TI Adolescent personality - A five-factor model construct validation SO ASSESSMENT LA English DT Article; Proceedings Paper CT 10th European Conference on Personality CY JUL 20, 2000 CL KRAKOW, POLAND DE adolescent personality measurement; construct validity; five-factor model ID CONFIRMATORY FACTOR-ANALYSIS; MULTITRAIT-MULTIMETHOD MATRIX; ADEQUATE TAXONOMY; NATURAL-LANGUAGE; SELF-REPORTS; FIT INDEXES; ACQUAINTANCESHIP; INVENTORY; CHILDHOOD; AGREEMENT AB The purpose of this study was to investigate convergent and discriminant validity of the five-factor model of adolescent personality in a school setting using three different raters (methods): self-ratings, peer ratings, and teacher ratings. The authors investigated validity through a multitrait-multimethod matrix and a confirmatory factor analysis correlated trait, uncorrelated method model. With the exception of Emotional Stability, each analysis demonstrated similar patterns and together provided support for the convergent and discriminant validity of the five-factor model structure of adolescent personality. However, among the three raters, self-ratings of personality provided a comparatively weaker method for assessing adolescent personality. The influences of agreement between self and other raters are discussed in relation to contrast, perceiver, and target effects; expert observer effects; the degree of acquaintanceship; and the effect of the social context. C1 Hampton Univ, Hampton, VA 23668 USA. Univ Georgia, McPhaul Ctr, Child & Family Dev Ctr, Athens, GA 30602 USA. RP Baker, SR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. EM spencer.baker@hamptonu.edu FU NIMH NIH HHS [MH53272] NR 68 TC 15 Z9 17 U1 15 U2 17 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD DEC PY 2004 VL 11 IS 4 BP 303 EP 315 DI 10.1177/1073191104269871 PG 13 WC Psychology, Clinical SC Psychology GA 869SX UT WOS:000225005600004 PM 15486167 ER PT J AU Gray, MJ Litz, BT Hsu, JL Lombardo, TW AF Gray, MJ Litz, BT Hsu, JL Lombardo, TW TI Psychometric properties of the life events checklist SO ASSESSMENT LA English DT Article DE potentially traumatic experiences; PTSD; trauma; assessment ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; BECK ANXIETY INVENTORY; TRAUMA; DEPRESSION; EXPOSURE; QUESTIONNAIRE; ADOLESCENTS; RELIABILITY; VALIDATION AB The Life Events Checklist (LEC), a measure of exposure to potentially traumatic events, was developed at the National Center for Posttraumatic Stress Disorder (PTSD) concurrently with the Clinician Administered PTSD Scale (CAPS) to facilitate the diagnosis of PTSD. Although the CAPS is recognized as the gold standard in PTSD symptom assessment, the psychometric soundness of the LEC has never been formally evaluated. The studies reported here describe the performance of the LEC in two samples: college undergraduates and combat veterans. The LEC exhibited adequate temporal stability, good convergence with an established measure of trauma history - the Traumatic Life Events Questionnaire (TLEQ) - and was comparable to the TLEQ in associations with variables known to be correlated with traumatic exposure in a sample of undergraduates. In a clinical sample of combat veterans, the LEC was significantly correlated, in the predicted directions, with measures of psychological distress and was strongly associated with PTSD symptoms. C1 Univ Wyoming, Laramie, WY 82071 USA. Boston VA Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Mississippi, University, MS 38677 USA. RP Gray, MJ (reprint author), Univ Wyoming, Laramie, WY 82071 USA. NR 40 TC 336 Z9 341 U1 2 U2 50 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD DEC PY 2004 VL 11 IS 4 BP 330 EP 341 DI 10.1177/1073191104269954 PG 12 WC Psychology, Clinical SC Psychology GA 869SX UT WOS:000225005600006 PM 15486169 ER PT J AU Shin, JM Sachs, G AF Shin, JM Sachs, G TI Differences in binding properties of two proton pump inhibitors on the gastric H+,K+-ATPase in vivo SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE the proton pump inhibitor; the residence time; the gastric H plus ,K plus -ATPase; binding sites; glutathione; stoichiometry ID ACID-SECRETION; COMPETITIVE INHIBITOR; OMEPRAZOLE ANALOGS; CHEMICAL-REACTIONS; CALCIUM-PUMP; H,K-ATPASE; ATPASE; PANTOPRAZOLE; MECHANISM; SCH28080 AB Restoration of acid secretion after treatment with covalently-bound proton pump inhibitors may depend on protein turnover and on reversal of inhibition by reducing agents such as glutathione. Glutathione incubation of the H+,K+-ATPase isolated from omeprazole or pantoprazole-treated rats reversed 88% of the omeprazole inhibition but none of the pantoprazole inhibition. The present study was designed to measure binding properties of omeprazole or pantoprazole in vivo. Rats were injected with C-14-omeprazole or C-14- pantoprazole after acid stimulation. The specific binding to the gastric H+,K+-ATPase was measured at timed intervals as well as reversal of binding by glutathione reduction. The stoichiometry of omeprazole and pantoprazole binding to the catalytic subunit of the H+,KATPase was 2 moles of inhibitor per mole of the H+,K+-ATPase phosphoenzyme. Omeprazole bound to one cysteine between transmembrane segments 5/6 and one between 7/8, pantoprazole only to the two cysteines in the TM5/6 domain. Loss of drug from the pump was biphasic, the fast component accounted for 84% of omeprazole binding and 51% of pantoprazole binding. Similarly, only 16% of omeprazole binding but 40% of pantoprazole binding was not reversed by glutathione. The residence time of omeprazole and pantoprazole on the ATPase in vivo depends on the reversibility of binding. Binding of pantoprazole at cysteine 822 is irreversible whereas that of omeprazole at cysteine 813 and 892 is reversible both in vivo and in vitro. This is consistent with the luminal exposure of cysteine 813 and 892 and the intra-membranal location of cysteine 822 in the 3D structure of the H+,K+-ATPase. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu FU NIDDK NIH HHS [DK46917]; PHS HHS [41301, 53462] NR 47 TC 33 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 1 PY 2004 VL 68 IS 11 BP 2117 EP 2127 DI 10.1016/j.bcp.2004.07.035 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 868ZP UT WOS:000224952200003 PM 15498502 ER PT J AU Shin, M Matsuda, K Ishii, O Terai, H Kaazempur-Mofrad, M Borenstein, J Detmar, M Vacanti, JP AF Shin, M Matsuda, K Ishii, O Terai, H Kaazempur-Mofrad, M Borenstein, J Detmar, M Vacanti, JP TI Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane) SO BIOMEDICAL MICRODEVICES LA English DT Article DE tissue engineering; replica molding; biocompatible polymer; endothelialization ID FIBROBLAST-GROWTH-FACTOR; FABRICATION; RELEASE; CELLS AB One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA 02129 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Charles Stark Draper Lab Inc, MEMS Technol Grp, Cambridge, MA 02139 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jvacanti@partners.org NR 21 TC 149 Z9 152 U1 3 U2 34 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD DEC PY 2004 VL 6 IS 4 BP 269 EP 278 DI 10.1023/B:BMMD.0000048559.29932.27 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 872AR UT WOS:000225178600002 PM 15548874 ER PT J AU Lerman, I Lozano, L Villa, AR Hernandez-Jimenez, S Weinger, K Caballero, AE Salinas, CA Velasco, ML Gomez-Perez, FJ Rull, JA AF Lerman, I Lozano, L Villa, AR Hernandez-Jimenez, S Weinger, K Caballero, AE Salinas, CA Velasco, ML Gomez-Perez, FJ Rull, JA TI Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Article DE adherence to treatment; Type 2 diabetes; depression ID ADHERENCE; DEPRESSION; AMERICANS; BEHAVIORS; MELLITUS; BARRIERS; OUTCOMES; PATIENT; REGIMEN; ADULTS AB To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% Cl 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% Cl 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively. (C) 2004 Elsevier SAS. All rights reserved. C1 Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Mexico City 14000, DF, Mexico. Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Clin Epidemiol Unit, Mexico City 14000, DF, Mexico. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lerman, I (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Endocrinol & Metab, Vasco Quiroga 15, Mexico City 14000, DF, Mexico. EM lerman@netservice.com.mx RI Lavbic, Dejan/G-1405-2010; HERNANDEZ-JIMENEZ, SERGIO/N-3091-2013 OI Lavbic, Dejan/0000-0003-2390-4160; HERNANDEZ-JIMENEZ, SERGIO/0000-0003-3080-8708 NR 35 TC 39 Z9 41 U1 3 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD DEC PY 2004 VL 58 IS 10 BP 566 EP 570 DI 10.1016/j.biopha.2004.09.003 PG 5 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 886TD UT WOS:000226250600005 PM 15589064 ER PT J AU Lui, KJ Zhou, XH Lin, CD AF Lui, KJ Zhou, XH Lin, CD TI Testing equality between two diagnostic procedures in paired-sample ordinal data SO BIOMETRICAL JOURNAL LA English DT Article DE type I error; equality; ordinal scale; sensitivity; specificity; paired-sample data ID OPERATING CHARACTERISTIC CURVES; MAXIMUM-LIKELIHOOD ESTIMATION; SIGNAL-DETECTION THEORY; EQUIVALENCE; PARAMETERS AB When a new diagnostic procedure is developed, it is important to assess whether the diagnostic accuracy of the new procedure is different from that of the standard procedure. For paired-sample ordinal data, this paper develops two test statistics for testing equality of the diagnostic accuracy between two procedures without assuming any parametric models. One is derived on the basis of the probability of correctly identifying the case for a randomly selected pair of a case and a non-case over all possible cutoff points, and the other is derived on the basis of the sensitivity and specificity directly. To illustrate the practical use of the proposed test procedures, this paper includes an example regarding the use of digitized and plain films for screening breast cancer. This paper also applies Monte Carlo simulation to evaluate the finite sample performance of the two statistics developed here and notes that they can perform well in a variety of situations. C1 San Diego State Univ, Dept Math & Stat, San Diego, CA 92182 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, HSR D Ctr Excellence, Seattle, WA 98108 USA. RP Lui, KJ (reprint author), San Diego State Univ, Dept Math & Stat, San Diego, CA 92182 USA. EM kjl@rohan.sdsu.edu NR 14 TC 2 Z9 2 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2004 VL 46 IS 6 BP 642 EP 652 DI 10.1002/bimj.200410062 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 884KJ UT WOS:000226083300002 ER PT J AU Kogan, JN Otto, MW Bauer, MS Dennehy, EB Miklowitz, DJ Zhang, HW Ketter, T Rudorfer, MV Wisniewski, SR Thase, ME Calabrese, J Sachs, GS AF Kogan, JN Otto, MW Bauer, MS Dennehy, EB Miklowitz, DJ Zhang, HW Ketter, T Rudorfer, MV Wisniewski, SR Thase, ME Calabrese, J Sachs, GS CA STEP-BD Investigators TI Demographic and diagnostic characteristics of the first 1000 patients enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; effectiveness research; illness description; sample characteristics ID MEDICATION ALGORITHM PROJECT; PHASE-3 TMAP-3; RATIONALE; HISTORY; ILLNESS; LITHIUM; DESIGN AB Objectives: Bipolar disorder is a severe, recurrent, and often highly impairing psychiatric disorder. The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) is a large-scale multicenter study funded by the National Institute of Mental Health (NIMH) to examine the longitudinal course of the disorder and the effectiveness of current treatments. The current report provides a context for interpreting studies resulting from STEP-BD by summarizing the baseline demographic and diagnostic characteristics of the first 1000 enrolled. Methods: The majority of the sample met DSM-IV criteria for bipolar I disorder (71%). Mean age of patients was 40.6 (+/-12.7) years and mean duration of bipolar illness was 23.1 (+/-12.9) years. Among the first 1000 subjects enrolled, 58.6% are females and 92.6% Caucasian. This report compares the STEP-BD sample with other large cohorts of bipolar patients (treatment and community samples). Results: Compared with US population and community studies, the first 1000 STEP-BD patients were less racially diverse, more educated, had lower income, and a higher unemployment rate. Results are discussed in terms of the contributions of STEP-BD (and other large-scale treatment studies) in understanding the nature, treatments, and outcomes of bipolar disorder for patients seeking care at academic treatment centers. Conclusions: The current report provides a context for interpreting future studies resulting from STEP-BD. The comparison of demographic and clinical characteristics between the samples across clinic-based studies suggests broad similarities despite the substantial differences in geography, payer mix, and clinical entry point. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Univ, Providence Vet Affairs Med Ctr, Providence, RI 02912 USA. So Methodist Univ, Dallas, TX 75275 USA. Univ Colorado, Boulder, CO 80309 USA. Univ Pittsburgh, Epidemiol Data Ctr, Pittsburgh, PA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. NIMH, Bethesda, MD 20892 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Kogan, JN (reprint author), Community Care Behav Hlth, 1 Chatham Ctr,Suite 700, Pittsburgh, PA 15219 USA. EM koganjn@ccbh.com OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 25 TC 68 Z9 69 U1 4 U2 6 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2004 VL 6 IS 6 BP 460 EP 469 DI 10.1111/j.1399-5618.2004.00158.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870TL UT WOS:000225081000003 PM 15541061 ER PT J AU Otto, MW Perlman, CA Wernicke, R Reese, HE Bauer, MS Pollack, MH AF Otto, MW Perlman, CA Wernicke, R Reese, HE Bauer, MS Pollack, MH TI Posttraumatic stress disorder in patients with bipolar disorder: a review of prevalence, correlates, and treatment strategies SO BIPOLAR DISORDERS LA English DT Review DE bipolar disorder; cognitive-behavior therapy; course; personality; pharmacotherapy; posttraumatic stress disorder (PTSD); prevalence; risk factors ID COGNITIVE-PROCESSING THERAPY; NATIONAL-COMORBIDITY-SURVEY; VEHICLE ACCIDENT SURVIVORS; COMBAT-RELATED PTSD; PANIC DISORDER; ADJUNCTIVE THERAPY; SOCIAL SUPPORT; LIFE EVENTS; OPEN-LABEL; SERTRALINE TREATMENT AB Objectives: In this article, we review the evidence for, and implications of, a high rate of comorbid posttraumatic stress disorder (PTSD) in individuals with bipolar disorder. Methods: We reviewed studies providing comorbidity data on patients with bipolar disorder, and also examined the PTSD literature for risk factors and empirically supported treatment options for PTSD. Results: Studies of bipolar patients have documented elevated rates of PTSD. Based on our review, representing 1214 bipolar patients, the mean prevalence of PTSD in bipolar patients is 16.0% (95% CI: 14-18%), a rate that is roughly double the lifetime prevalence for PTSD in the general population. Risk factors for PTSD that are also characteristic of bipolar samples include the presence of multiple axis I disorders, greater trauma exposure, elevated neuroticism and lower extraversion, and lower social support and socio-economic status. Conclusions: These findings are discussed in relation to the cost of PTSD symptoms to the course of bipolar disorder. Pharmacological and cognitive-behavioral treatment options are reviewed, with discussion of modifications to current cognitive-behavioral protocols for addressing PTSD in individuals at risk for mood episodes. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Univ, Providence Vet Affairs Med Ctr, Providence, RI 02912 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,6th Floor, Boston, MA 02215 USA. EM mwotto@bu.edu NR 105 TC 58 Z9 59 U1 4 U2 13 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD DEC PY 2004 VL 6 IS 6 BP 470 EP 479 DI 10.1111/j.1399-5618.2004.00151.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 870TL UT WOS:000225081000004 PM 15541062 ER PT J AU Shipp, TD Shipp, DZ Bromley, B Sheahan, R Cohen, A Lieberman, E Benacerraf, B AF Shipp, TD Shipp, DZ Bromley, B Sheahan, R Cohen, A Lieberman, E Benacerraf, B TI What factors are associated with parents' desire to know the sex of their unborn child ? SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article; Proceedings Paper CT 10th Congress of the World-Federation-for-Ultrasound-in-Medicine-and-Biology CY JUN 01-04, 2003 CL MONTREAL, CANADA SP World Fed Ultrasound Med Bio ID ULTRASOUND AB Background: Parents feel strongly about whether or not to learn the sex of their fetus. We sought to determine which factors are significantly associated with parents' desire to know or not to know the fetal sex during a prenatal ultrasound. Methods: All women undergoing prenatal ultrasound examinations, except for those with suspected failed pregnancies, were invited to answer a questionnaire at an outpatient referral center for diagnostic ultrasound in obstetrics and gynecology in Boston, Massachusetts. The survey asked about demographic factors, current pregnancy, and past pregnancies, and an open-ended question about whether and why the parents wished to learn, or did not learn, the sex of their fetus. Factors significantly associated with parents' desire to learn the fetal sex prenatally were determined and analyzed. Results: A total of 1,340 questionnaires were completed. Overall, 761/1,302 (58%) of mothers and 747/1,295 (58%) of fathers learned or planned to learn the fetal sex before delivery. Factors most associated with wanting to learn the fetal sex were conceiving accidentally, finding out the sex in a previous pregnancy, not planning to breastfeed, influence of sex on future childbearing plans, planning a move or renovation dependent on sex, and specific parental sex preference. Demographic factors most associated with wanting to learn the fetal sex were father without full-time job, lower household income, unwed mother, maternal age less than 22 or greater than 40 years, no college degree, race other than white, and religion other than Catholic. Conclusions: Specific demographic and socioeconomic characteristics predicted whether or not parents chose to know the sex of their unborn child. Families in which the pregnancy was unplanned, those in which fetal sex would influence living arrangements or future childbearing plans, and those of lower socioeconomic status wished to know the sex more frequently. Further study is needed to understand parents' motivations underlying the desire to know or not know fetal sex before delivery. C1 Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Social Serv League, Cohasset, MA USA. RP Shipp, TD (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Sch Med, CWN 3,75 Francis St, Boston, MA 02115 USA. NR 14 TC 16 Z9 16 U1 0 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD DEC PY 2004 VL 31 IS 4 BP 272 EP 279 DI 10.1111/j.0730-7659.2004.00319.x PG 8 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 870MJ UT WOS:000225060900004 PM 15566339 ER PT J AU Armstrong, SA AF Armstrong, SA TI Leukemia gene expression: MLL rearrangements in AML and ALL SO BLOOD LA English DT Editorial Material C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Armstrong, SA (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2004 VL 104 IS 12 BP 3423 EP 3424 DI 10.1182/blood-2004-09-3504 PG 2 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600008 ER PT J AU Hess, C Means, TK Autissier, P Woodberry, T Altfeld, M Addo, MM Frahm, N Brander, C Walker, BD Luster, AD AF Hess, C Means, TK Autissier, P Woodberry, T Altfeld, M Addo, MM Frahm, N Brander, C Walker, BD Luster, AD TI IL-8 responsiveness defines a subset of CD8 T cells poised to kill SO BLOOD LA English DT Article ID DENDRITIC CELLS; LYMPHOCYTES; MEMORY; DIFFERENTIATION; CHEMOKINES; INFECTION; EXPRESSION; RECEPTORS; MIGRATION; MATURATION AB CD8 T cells play a key role in host defense against intracellular pathogens. Efficient migration of these cells into sites of infection is therefore intimately linked to their effector function. The molecular mechanisms that control CD8 T-cell trafficking into sites of infection and inflammation are not well understood, but the chemokine/chemokine receptor system is thought to orchestrate this process. Here we systematically examined the chemokine receptor profile expressed on human CD8 T cells. Surprisingly, we found that CXC chemokine receptor 1 (CXCR1), the predominant neutrophil chemokine receptor, defined a novel interleukin-8/CXC ligand 8 (IL-8/CXCL8)-responsive CD8 T-cell subset: that was enriched in perforin, granzyme B, and interferon-gamma (IFNgamma), and had high cytotoxic potential. CXCR1 expression was down-regulated by antigen stimulation both in vitro and in vivo, suggesting andgen-dependent shaping of the migratory characteristics of CD8 T cells. On virus-specific CD8 T cells from persons with a history of Epstein-Barr virus (EBV) and influenza infection, CXCR1 expression was restricted to terminally dif- ferentiated effector memory cells. In HIV-11 infection, CXCR1 -expressing HIV-1-specific CD8 T cells were present only in persons who were able to control HIV-11 replication during structured treatment interruptions. Thus, CXCR1 identifies a subset of CD8 T cells poised for immediate cytotoxicity and early recruitment into sites of innate immune system activation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div AIDS, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis,Dept Med, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Bldg 149,13th St, Charlestown, MA 02129 USA. EM luster@helix.mgh.harvard.edu OI Brander, Christian/0000-0002-0548-5778 NR 40 TC 46 Z9 46 U1 2 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 DEC 1 PY 2004 VL 104 IS 12 BP 3463 EP 3471 DI 10.1182/blood-2004-03-1067 PG 9 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600016 PM 15292066 ER PT J AU Tassone, P Goldmacher, VS Neri, P Gozzini, A Shammas, MA Whiteman, KR Hylander-Gans, LL Carrasco, DR Hideshima, T Shringarpure, R Shi, JL Allam, CK Wijdenes, J Venuta, S Munshi, NC Anderson, KC AF Tassone, P Goldmacher, VS Neri, P Gozzini, A Shammas, MA Whiteman, KR Hylander-Gans, LL Carrasco, DR Hideshima, T Shringarpure, R Shi, JL Allam, CK Wijdenes, J Venuta, S Munshi, NC Anderson, KC TI Cytotoxic activity of the maytansinoid immunoconjugate B-B4-DM1 against CD138(+) multiple myeloma cells SO BLOOD LA English DT Article ID SCID-HU MOUSE; MYELOBLASTIC-LEUKEMIA CELLS; BONE-MARROW BIOPSIES; MONOCLONAL-ANTIBODIES; PLASMA-CELLS; GEMTUZUMAB OZOGAMICIN; PERIPHERAL-BLOOD; SYNDECAN-1; CANCER; THERAPY AB We tested the in vitro and in vivo antitumor activity of the maytansinoid DM1 (N-2'-deacetyl-N-2'-(3-mercapto-1-oxopropyl)-maytansine), a potent antimicrotubule agent, covalently linked to the murine monoclonal antibody (mAb) B-B4 targeting syndecan-1 (CD138). We evaluated the in vitro activity of B-B4-DM1 against a panel of CD138(+) and CD138(-) cell lines, as well as CD138(+) patient multiple myeloma (MM) cells. Treatment with B-M-M selectively decreased growth and survival of MM cell lines, patient MM cells, and MM cells adherent to bone marrow stromal cells. We further examined the activity of B-B4-DM1 in 3 human MM models in mice: (1) severe combined immunodeficient (SCID) mice bearing subcutaneous xenografts; (2) SCID mice bearing green fluorescent protein-positive (GFP(+)) xenografts; and (3) SCID mice implanted with human fetal bone (SCID-hu) and subsequently injected with patient MM cells. Tumor regression and Inhibition of tumor growth, improvement in overall survival, and reduction in levels of circulating human paraprotein were observed in mice treated with B-B4-DM1. Although immunohistochemical analysis demonstrates restricted CD138 expression In human tissues, the lack of B-B4 reactivity with mouse tissues precludes evaluation of its toxicity in these models. In conclusion, B-B4-DM1 is a potent anti-MM agent that kills cells in an antigen-dependent manner in vitro and mediates in vivo antitumor activity at doses that are well tolerated, providing the rationale for clinical trials of this immunoconjugate in MM. (C) 2004 by The American Society of Hematology. C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia, Catanzaro, Italy. ImmunoGen, Cambridge, MA USA. Diaclone Res, Besancon, France. RP Anderson, KC (reprint author), Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU PHS HHS [R01-50947, P01-78378, P50-100707] NR 58 TC 89 Z9 92 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 DEC 1 PY 2004 VL 104 IS 12 BP 3688 EP 3696 DI 10.1182/blood-2004-03-0963 PG 9 WC Hematology SC Hematology GA 874LJ UT WOS:000225351600048 PM 15292058 ER PT J AU Means, RT AF Means, RT TI Hepcidin and anaemia SO BLOOD REVIEWS LA English DT Review DE anaemia of chronic disease; cytokines; ferritin; inflammation; hepcidin; inflammation; iron ID TUMOR-NECROSIS-FACTOR; ANTIMICROBIAL PEPTIDE HEPCIDIN; MACROPHAGE IRON-METABOLISM; COLONY-FORMING-UNITS; CHRONIC DISEASE; TRANSFERRIN RECEPTOR; NITRIC-OXIDE; HEREDITARY HEMOCHROMATOSIS; RHEUMATOID-ARTHRITIS; BONE-MARROW AB The anaemia of chronic disease (ACD) is a common haematologic syndrome characterized by hypoferraemia with adequate reticuloendothetial iron stores. Frequently, serum ferritin concentration in these patients is elevated. The pathogenesis of ACD involves abnormalities in red cell survival, the erythropoietic response to anaemia, and in iron metabolism. Hepcidin is an antibacterial protein produced in the liver which can be found in blood or urine, and which participates in host defense. Recent studies have demonstrated that hepcidin is a key regulator of iron balance in the intestinal mucosa, and that abnormalities in hepcidin gene expression are associated with clinical abnormalities in iron parameters and, in some cases, with anaemia. Hepcidin is an acute-phase reacting protein, and it has been suggested that hepcidin is the key mediator of ACD. Investigation of hepcidin production in either serum or urine demonstrates a strong correlation with serum ferritin concentration. Differences between the hepcidin concentrations observed in ACD (or syndromes resembling ACD) and those observed in iron deficiency may depend on the definition used for the anaemia syndrome. It seems very likely that hepcidin is a major contributor to iron abnormalities characteristic of ACD; whether it contributes to the pathogenesis of the syndrome in a broader sense remains to be determined by further investigation. Published by Elsevier Ltd. C1 Ralph H Johnson VA Med Ctr, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Means, RT (reprint author), Ralph H Johnson VA Med Ctr, Dept Med, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM meansr@musc.edu RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL-69418] NR 48 TC 38 Z9 41 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD DEC PY 2004 VL 18 IS 4 BP 219 EP 225 DI 10.1016/S0268-960X9(03)00066-3 PG 7 WC Hematology SC Hematology GA 867ZY UT WOS:000224882800001 PM 15501550 ER PT J AU Walsh, T Morris, AK Holle, LM Callander, N Bradshaw, P Valley, AW Clark, G Freytes, CO AF Walsh, T Morris, AK Holle, LM Callander, N Bradshaw, P Valley, AW Clark, G Freytes, CO TI Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic stem cell transplant patients: results of a prospective, double-blind, randomized trial SO BONE MARROW TRANSPLANTATION LA English DT Article DE hematopoietic stem cell transplantation; nausea; vomiting; granisetron; ondansetron ID HIGH-DOSE CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; CISPLATIN-INDUCED EMESIS; TOTAL-BODY IRRADIATION; ANTIEMETIC EFFICACY; INTRAVENOUS ONDANSETRON; DOLASETRON MESILATE; ORAL GRANISETRON; PROPHYLAXIS; CYCLOPHOSPHAMIDE AB The serotonin type- 3 ( 5- HT3) antagonists represent a significant advance in the prevention of acute nausea and vomiting ( N/ V) from highly emetogenic chemotherapy. We sought to determine if any differences in efficacy or adverse effects exist between two such agents, ondansetron and granisetron, during conditioning therapy for hematopoietic stem cell transplantation ( HSCT). Patients were randomized to receive either ondansetron 0.15 mg/ kg intravenously every 8 h or granisetron 10 mug/ kg intravenously daily. Additionally, all patients received scheduled dexamethasone and lorazepam. Prophylaxis was continued until 24 h after completion of chemotherapy. Nausea and distress were measured subjectively with visual analog scales and emetic episodes were quantified. Of the 110 randomized patients, 96 were evaluable for efficacy and safety. No significant differences in efficacy were observed between the ondansetron- and granisetron- treated patients, evaluated by comparing the degree of nausea and distress, number of emetic episodes and overall control of emesis. The adverse effects were also comparable and no patients were removed from study because of severe toxicities. This trial demonstrates that ondansetron and granisetron are equally effective at preventing acute N/ V associated with conditioning therapy frequently used for HSCT. The agent of choice should be based on drug acquisition cost or preference. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Duke Univ, Med Ctr, Durham, NC USA. Syntaxx Commun Inc, Storrs, CT USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Pharm Healthcare Solut, San Antonio, TX USA. OSI Pharmaceut Inc, Boulder, CO USA. RP Walsh, T (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, 7400 Merton Minter Blvd,Dept 119, San Antonio, TX 78229 USA. EM dveblu@aol.com NR 23 TC 12 Z9 14 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2004 VL 34 IS 11 BP 963 EP 968 DI 10.1038/sj.bmt.1704714 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 871UQ UT WOS:000225159800007 PM 15489869 ER PT J AU Ho, VT Kim, HT Li, S Hochberg, EP Cutler, C Lee, SJ Fisher, DC Milford, E Kao, G Daley, H Levin, J Ng, A Mauch, P Alyea, EP Antin, JH Soiffer, RJ AF Ho, VT Kim, HT Li, S Hochberg, EP Cutler, C Lee, SJ Fisher, DC Milford, E Kao, G Daley, H Levin, J Ng, A Mauch, P Alyea, EP Antin, JH Soiffer, RJ TI Partial CD8+ T-cell depletion of allogeneic peripheral blood stem cell transplantation is insufficient to prevent graft-versus-host disease SO BONE MARROW TRANSPLANTATION LA English DT Article DE T-cell depletion; CD8 T cells; GVHD; hematopoietic stem cell transplantation; graft-versus-leukemia ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; DONOR LYMPHOCYTE INFUSION; SELECTIVE DEPLETION; RISK-FACTORS; TRIAL; RECONSTITUTION; RECIPIENTS; CHIMERISM; RELAPSE AB Prior studies suggest that depletion of CD8+ T cells from donor bone marrow or donor lymphocyte infusions can reduce graft- versus- host disease ( GVHD) without compromising graft- versus- leukemia. We explored CD8 depletion in patients undergoing matched related donor ( MRD, n = 25) and unrelated donor ( URD, n = 16) peripheral blood stem cell transplantation following myeloablative conditioning with cyclophosphamide ( 60 mg/ kg/ day i. v. x 2) and total body irradiation ( 200 cGy x 7 fractions). Ex vivo incubation of mobilized donor peripheral blood cells with anti- CD8 antibody coated high- density microparticles removed 99% of CD8+ cells. The median number of CD8+ cells infused was 3.9 x 10(5) cells/ kg ( 2.2 x 10(5) in MRD, and 8.1 x 10(5) in URD patients). Post transplant immune suppression included tacrolimus in the MRD cohort, and tacrolimus plus mini- methotrexate ( 5 mg/ m(2) days + 1, 3, 6, 11) in the URD cohort. All 41 patients engrafted. Grade 2 - 4 acute GVHD incidence was 61% ( 44% MRD, 88% URD). Chronic GVHD incidence was 50% ( 48% MRD, 55% URD). Relapse incidence was 4.9%. Estimated event- free and overall survival rates were 65 and 63%, respectively, at 1 year and 56 and 57%, respectively, at 2 years. There was no correlation between CD8+ number and GVHD or survival. A 2- log depletion of CD8+ cells from PBSC is insufficient to prevent GVHD. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. RP Ho, VT (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D1B21, Boston, MA 02115 USA. EM vtho@partners.org FU NHLBI NIH HHS [HL70149-01A1]; NIAID NIH HHS [AI29530] NR 31 TC 20 Z9 20 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2004 VL 34 IS 11 BP 987 EP 994 DI 10.1038/sj.bmt.1704690 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 871UQ UT WOS:000225159800011 PM 15489873 ER PT J AU Zook, NA Davalos, DB DeLosh, EL Davis, HP AF Zook, NA Davalos, DB DeLosh, EL Davis, HP TI Working memory, inhibition, and fluid intelligence as predictors of performance on Tower of Hanoi and London tasks SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT 73rd Annual Convention of the Rocky-Mountain-Psychological-Association CY APR 11-13, 2003 CL Denver, CO SP Rocky Mt Psychol Assoc DE executive function; Tower of London; Tower of Hanoi; working memory; inhibition; fluid intelligence; matrix reasoning ID CARD SORTING TEST; FRONTAL-LOBE; INTERFERENCE; INFORMATION AB The contributions of working memory, inhibition, and fluid intelligence to performance on the Tower of Hanoi (TOH) and Tower of London (TOL) were examined in 85 undergraduate participants. All three factors accounted for significant variance on the TOH, but only fluid intelligence accounted for significant variance on the TOL. When the contribution of fluid intelligence was accounted for, working memory and inhibition continued to account for significant variance on the TOH. These findings support Duncan, Burgess, and Emslie's (1995) argument that fluid intelligence contributes to executive functioning, but also show that the executive processes elicited by tasks vary according to task structure. (C) 2004 Elsevier Inc. All rights reserved. C1 Colorado State Univ, Dept Psychol, Ft Collins, CO 80543 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Dept Psychol, Colorado Springs, CO 80907 USA. RP Zook, NA (reprint author), Colorado State Univ, Dept Psychol, Ft Collins, CO 80543 USA. EM nazook@lamar.colostate.edu NR 30 TC 49 Z9 56 U1 6 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD DEC PY 2004 VL 56 IS 3 BP 286 EP 292 DI 10.1016/j.bandc.2004.07.003 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 872LT UT WOS:000225209400002 PM 15522766 ER PT J AU Goldhirsch, A Goldhirsch, A Goldhirsch, A Gelber, RD AF Goldhirsch, A Goldhirsch, A Goldhirsch, A Gelber, RD TI Life with consequences of breast cancer: pregnancy during and after endocrine therapies SO BREAST LA English DT Editorial Material ID TAMOXIFEN; WOMEN C1 Oncol Inst So Switzerland, Div Med Oncol, Bellinzona, Switzerland. Inst Breast Canc Study Grp, Bern, Switzerland. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Stat Ctr Int Breast Canc Study Grp, Boston, MA 02115 USA. European Inst Oncol, Dept Med, Milan, Italy. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Via Ripamonti 435, Milan, Italy. EM aron.goldhirsch@ibcsg.org; aron.goldhirsch@ibcsg.org; aron.goldhirsch@ibcsg.org NR 12 TC 8 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2004 VL 13 IS 6 BP 443 EP 445 DI 10.1016/j.breast.2004.08.015 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 880AF UT WOS:000225760000001 PM 15563849 ER PT J AU Etzioni, DA Ponce, NA Babey, SH Spencer, BA Brown, ER Ko, CY Chawla, N Breen, N Klabunde, CN AF Etzioni, DA Ponce, NA Babey, SH Spencer, BA Brown, ER Ko, CY Chawla, N Breen, N Klabunde, CN TI A population-based study of colorectal cancer test use - Results from the 2001 California Health Interview Survey SO CANCER LA English DT Article DE colorectal neoplasms; prevention and control; mass screening; ethnic; groups; statistics and numeric data; endoscopy; utilization; occult blood; California ID PRIMARY-CARE; LOW-INCOME; UNITED-STATES; BARRIERS; ACCESS; WOMEN; ASSOCIATION; PREDICTORS; INSURANCE; PROGRESS AB BACKGROUND. Recent research has supported the use of colorectal cancer (CRC) tests to reduce disease incidence, morbidity, and mortality. A new health survey has provided an opportunity to examine the use of these tests in California's ethnically diverse population. The authors used the 2001 California Health Interview Survey (CHIS 2001) to evaluate 1) rates of CRC test use, 2) predictors of the receipt of tests, and 3) reasons for nonuse of CRC tests. METHODS. The CHIS 2001 is a random-digit dial telephone survey that was conducted in California. Responses were analyzed from 22,343 adults age greater than or equal to 50 years. CRC test use was defined as receipt of a fecal occult blood test in the past year and/or receipt of an endoscopic examination in the past 5 years. RESULTS. Nearly 54% of California adults reported receipt of a recent CRC test. Insurance coverage and having a usual source of care were the most important predictors of CRC testing. Latinos age < 65 years were less likely to be tested than whites (relative risk [RR], 0.84; 95% confidence interval [95% CI], 0.77-0.92). Men were more likely to be tested than women, an effect that was greater among individuals age 50-64 years (RR, 1.28; 95% CI, 1.23-1.32) than among individuals age 65 years (RR, 1.19; 95% CI, 1.15-1.23). Women were more likely than men to say that their physician did not inform them the test was needed and that CRC tests were painful or embarrassing. CONCLUSIONS. Results of the current study indicate a need for physicians to recommend CRC testing to their patients. Assuring that all individuals have both health insurance and a usual source of care would help address gaps in the receipt of CRC tests. (C) 2004 American Cancer Society. C1 Univ Calif Los Angeles, Ctr Hlth Policy Res, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Dept Med, Los Angeles, CA USA. RAND, Santa Monica, CA USA. NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. RP Ponce, NA (reprint author), Univ Calif Los Angeles, Ctr Hlth Policy Res, Dept Hlth Serv, 10911 Weyburn Ave,Suite 300, Los Angeles, CA 90024 USA. EM nponce@ucla.edu OI Ponce, Ninez/0000-0001-5151-6718 FU NCI NIH HHS [N02PC95057] NR 31 TC 80 Z9 81 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2004 VL 101 IS 11 BP 2523 EP 2532 DI 10.1002/cncr.20692 PG 10 WC Oncology SC Oncology GA 873ZS UT WOS:000225321300005 PM 15505783 ER PT J AU Earle, CC Kwok, A Gazelle, GS Fuchs, CS AF Earle, CC Kwok, A Gazelle, GS Fuchs, CS TI Two schedules of second-line irinotecan for metastatic colon carcinoma - Economic evaluation of a randomized trial SO CANCER LA English DT Article DE colorectal neoplasms; economic evaluation; irinotecan; phase III clinical trial ID COLORECTAL-CANCER; FLUOROURACIL FAILURE AB BACKGROUND. in a recently reported, randomized trial, it was found that a regimen of irinotecan once every 3 weeks for patients with advanced colorectal carcinoma was associated with a lower incidence of severe diarrhea compared with weekly treatment, and both regimens had similar efficacy. METHODS. Resource utilization was captured prospectively for all 291 patients who were included in the trial. Utilities were estimated by transformation of the global quality-of-life (QOL) item on the Eastern Organization for Research and Treatment of Cancer QLQ-C30 instrument. RESULTS. Patients in the every-3-week arm incurred an average incremental cost of $1362, because they received higher average weekly doses and because the every-3-week regimen resulted in less toxicity, allowing delivery of 97% of the planned doses compared with delivery of only 75% of the planned doses in the weekly arm. This lower toxicity also resulted in offsetting savings from decreased hospitalization and less requirement for supportive medications. Non-chemotherapy-related treatment administration costs also were lower, because the every-3-week regimen could be delivered with half the number of infusions. Utility declined less in the every-3-week arm, resulting in a saving of 6.3 quality-adjusted days. The base-case cost:utility ratio was $78,627 per quality-adjusted life year for patients on the every-3-week schedule. However, that ratio was very sensitive to the cost of irinotecan. CONCLUSIONS. The schedule of irinotecan once every 3 weeks schedule was more costly but achieved lower toxicity, resulting in modestly improved utility. The cost-per-utility ratio was comparable to other commonly accepted contemporary treatments. (C) 2004 American Cancer Society. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. Pfizer Inc, Stat Operat, Markham, ON, Canada. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 12 TC 7 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2004 VL 101 IS 11 BP 2533 EP 2539 DI 10.1002/cncr.20691 PG 7 WC Oncology SC Oncology GA 873ZS UT WOS:000225321300006 PM 15503310 ER PT J AU Ghobrial, IM Fonseca, R Greipp, PR Blood, E Rue, M Vesole, DH Gertz, MA AF Ghobrial, IM Fonseca, R Greipp, PR Blood, E Rue, M Vesole, DH Gertz, MA TI Initial immunoglobulin M 'Flare' after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia an eastern cooperative oncology group study SO CANCER LA English DT Article DE Waldenstrom macroglobulinemia; immunoglobulin; rituximab; response ID ANTIBODY-MEDIATED IMMUNOTHERAPY; FLUDARABINE THERAPY AB BACKGROUND. The goal of the current Study was to characterize the initial upsurge in immunoglobulin M (IgM) levels after treatment with rituximab in patients with Waldenstrom macroglobulinemia (WM). METHODS. As part of a Phase II Eastern Cooperative Oncology Group study, 72 patients were treated with rituximab (375 Mg/m(2) weekly for 4 weeks) between April 2000 and January 2002. IgM levels in these patients were measured at five separate time points so that any temporal changes that occurred could be characterized. RESULTS. Of the 54 patients for whom the relevant IgM measurements were available, 29 (54%) experienced an increase in IgM levels between baseline and the first scheduled postbaseline time point. At 2 months, 13 of 22 evaluable patients (59%) continued to have elevated IgM levels, and at 4 months, elevated IgM levels persisted in 4 of 15 evaluable patients (27%). Overall, a nonlinear trend characterized by an initial increase in IgM levels followed by a decrease in these levels was observed (P < 0.0001). CONCLUSIONS. Treating physicians should be aware that an IgM 'flare' may occur in up to 54% of patients treated with rituximab; however, most of these patients experience a decrease in IgM levels within 4 months after the initiation of therapy. Therefore, patients should not be discouraged from continuing to receive this potentially effective therapeutic agent, as responses to rituximab may develop slowly. Longer follow-up will reveal whether patients who experience an upsurge in IgM levels have poorer overall survival or shorter times to progression compared with patients who do not experience this IgM flare. Factors predicting an initial increase in IgM levels could not be identified. (C) 2004 American Cancer Society. C1 Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Med Coll Wisconsin, Dept Internal Med, Div Hematol Oncol, Milwaukee, WI 53226 USA. RP Gertz, MA (reprint author), Mayo Clin, Mayo Fdn, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM Gertz.morie@mayo.edu RI Rue, Montserrat/B-5663-2009; OI Rue, Montserrat/0000-0002-7862-9365; Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [CA21115, CA P50 CA97274, CA13650, CA17145, CA23318, CA66636] NR 18 TC 82 Z9 82 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2004 VL 101 IS 11 BP 2593 EP 2598 DI 10.1002/cncr.20658 PG 6 WC Oncology SC Oncology GA 873ZS UT WOS:000225321300013 PM 15493038 ER PT J AU Macpherson, GR Singh, AS Bennett, CL Venzon, DJ Liewehr, DJ Franks, ME Dahut, WL Kantoff, PW Price, DK Figg, WD AF Macpherson, GR Singh, AS Bennett, CL Venzon, DJ Liewehr, DJ Franks, ME Dahut, WL Kantoff, PW Price, DK Figg, WD TI Genotyping and functional analysis of the D104N variant of human endostatin SO CANCER BIOLOGY & THERAPY LA English DT Article DE endostatin; prostate cancer; angiogenesis; single nucleotide polymorphism ID RECOMBINANT HUMAN ENDOSTATIN; ANGIOGENESIS INHIBITOR ENDOSTATIN; ADVANCED SOLID TUMORS; PROSTATE-CANCER; IN-VITRO; PHASE-I; ANTIANGIOGENIC THERAPY; ANTITUMOR-ACTIVITY; ENDOTHELIAL-CELLS; HEPARAN-SULFATE AB Endostatin is an endogenous inhibitor of angiogenesis derived from the extracellular matrix protein collagen XVIII. It has been reported that a variation at the 104 position (D104N) of human endostatin is associated with an increased risk of prostate cancer, potentially indicating that this protein variant is less active as an anti-angiogenic agent. Herein we reported the results of genotyping 389 patients with androgen independent prostate cancer ( AIPC) and 352 normal control individuals for D104N endostatin. There was no significant association between the frequency of 104N endostatin and the incidence of AIPC in either Caucasian or African American patients compared to controls (15% Caucasian AIPC versus 13.7% in Caucasian controls, p=0.79; 7.4% African American AIPC versus 5.6% in African American controls, p=0.64). Actuarial analysis revealed no statistically significant association between incidence of the DN heterozygous genotype and survival (p=0.62 by logrank test). To study the functional significance of the D104N conversion, we have expressed and purified insoluble recombinant human 104D and 104N endostatin and compared their respective activities in human umbilical vein endothelial cell ( HUVEC) tube formation assays. The 104N variant of human endostatin inhibited HUVEC tube formation at least as well as the wild-type form. We concluded that the D104N variation in human endostatin is neither clinically relevant nor suitable as a pharmacogenomic endpoint to assess the risk for developing AIPC. C1 NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core,Biostat & Data Management, NIH,Mol Pharmacol Lab, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, VA Chicago Healthcare Syst Lakeside, Chicago, IL 60611 USA. Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, Bethesda, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Figg, WD (reprint author), NCI, Med Oncol Clin Res Unit, Clin Pharmacol Res Core,Biostat & Data Management, NIH,Mol Pharmacol Lab, Bldg 10,Rm 5A01,MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Venzon, David/B-3078-2008; Bennett, Charles/C-2050-2008; Figg Sr, William/M-2411-2016 NR 37 TC 11 Z9 11 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD DEC PY 2004 VL 3 IS 12 BP 1298 EP 1303 PG 6 WC Oncology SC Oncology GA 918WJ UT WOS:000228578000030 PM 15662127 ER PT J AU Wang, LI Giovannucci, EL Hunter, D Neuberg, D Su, L Christiani, DC AF Wang, LI Giovannucci, EL Hunter, D Neuberg, D Su, L Christiani, DC TI Dietary intake of Cruciferous vegetables, Glutathione S-transftrase (GST) polymorphisms and lung cancer risk in a Caucasian population SO CANCER CAUSES & CONTROL LA English DT Article DE cruciferous vegetables; GSTM1; GSTT1; lung cancer; gene-environment interaction ID GENE-ENVIRONMENT INTERACTIONS; TRANSFERASE POLYMORPHISMS; SAMPLE-SIZE; ISOTHIOCYANATES; ENZYMES; MISCLASSIFICATION; REPRODUCIBILITY; QUESTIONNAIRE; EPIDEMIOLOGY; GENOTYPES AB Objective: To evaluate possible interactions between dietary intake of cruciferous vegetables and the glutathione s-transferase mu and theta (GSTM1 and GSTT1) genotypes in lung cancer risk. Methods: Hospital-based case-control study of 716 Caucasian lung cancer cases and 939 spouse and friend controls conducted in Boston, Massachussetts between 1992 and 2000. Dietary intake was collected through a food frequency questionnaire and blood was obtained for genotyping. Logistic regression models were adjusted for age, gender.. total calories and smoking variables. Results: Higher intakes of cruciferous vegetables reduced lung cancer risk among GSTM1 present individuals (odds ratio (OR)(higher versus lowest tertile) 0.61, 95% confidence interval (CI) = 0.39-0.95) but not among GSTM1 null individuals (ORhighest (versus lowest tertile) = 1.15, 95% CI = 0.78-1.68). We observed statistically significant interactions between GSTM1 and cruciferous vegetable intake overall (likelihood ratio test (LRT): p = 0.05) and among current smokers (LRT: p = 0.01). No significant interactions were observed for GSTT1 or the combined GSTM1/T1 genotype. Conclusions: In our study, higher cruciferous vegetable intake reduced lung cancer risk only among individuals with the GSTM1 present genotype. Our findings differed from prior studies that specifically assessed isothiocyanates found in cruciferous vegetables or evaluated Asian study populations with higher levels of cruciferous vegetable consumption. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Occupat Hlth Program, 665 Huntington Ave,Bldg 1 Room 1402, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Barickman, Thomas/I-6993-2012 FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES/CA 06409, ES00002]; ODCDC CDC HHS [CCT1120421] NR 30 TC 85 Z9 94 U1 1 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2004 VL 15 IS 10 BP 977 EP 985 DI 10.1007/s10552-004-1093-1 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 891LR UT WOS:000226583100001 PM 15801482 ER PT J AU Winkler, F Kozin, SV Tong, RT Chae, SS Booth, MF Garkavtsev, I Xu, L Hicklin, DJ Fukumura, D di Tomaso, E Munn, LL Jain, RK AF Winkler, F Kozin, SV Tong, RT Chae, SS Booth, MF Garkavtsev, I Xu, L Hicklin, DJ Fukumura, D di Tomaso, E Munn, LL Jain, RK TI Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: Role of oxygenation, angiopoietin-1, and matrix metal loproteinases SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSELS; IONIZING-RADIATION; CELL APOPTOSIS; IN-VIVO; BASEMENT-MEMBRANE; TIE2 RECEPTOR; ANGIOGENESIS; CANCER; ANTIBODY AB The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalization window" - a period during which combined radiation therapy gives the best outcome. This window is characterized by an increase in tumor oxygenation, which is known to enhance radiation response. During the normalization window, but not before or after it, VEGFR2 blockade increases pericyte coverage of brain tumor vessels via upregulation of Ang1 and degrades their pathologically thick basement membrane via MMP activation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. ImClone Syst Inc, New York, NY 10014 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 50 TC 728 Z9 774 U1 7 U2 49 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2004 VL 6 IS 6 BP 553 EP 563 DI 10.1016/S1535-6108(04)00305-8 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 884HX UT WOS:000226076600006 PM 15607960 ER PT J AU Du, JY Widlund, HR Horstmann, MA Ramaswamy, S Ross, K Huber, WE Nishimura, EK Golub, TR Fisher, DE AF Du, JY Widlund, HR Horstmann, MA Ramaswamy, S Ross, K Huber, WE Nishimura, EK Golub, TR Fisher, DE TI Critical role of CDK2 for melanoma growth linked to its melanocyte-specific transcriptional regulation by MITF SO CANCER CELL LA English DT Article ID CYCLIN-DEPENDENT KINASES; WAARDENBURG-SYNDROME; MICROPHTHALMIA GENE; HUMAN HOMOLOG; FACTOR FAMILY; EXPRESSION; ACTIVATION; PROTEIN; CELLS; MICE AB The genomic organization of the CDK2 gene; which overlaps the melanocyte-specific gene SILV/PMEL17, poses an interesting regulatory challenge. We show that, despite its ubiquitous expression, CDK2 exhibits tissue-specific regulation by the essential melanocyte lineage transcription factor MITF. In addition, functional studies revealed this regulation to be critical for maintaining CDK2 kinase activity and growth of melanoma cells. Expression levels of MITF and CDK2 are tightly correlated in primary melanoma specimens and predict susceptibility to the CDK2 inhibitor roscovitine. CDK2 depletion suppressed growth and cell cycle progression in melanoma, but not other cancers, corroborating previous results. Collectively, these data indicate that CDK2 activity in melanoma is largely maintained at the transcriptional level by MITF, and unlike other malignancies, it may be a suitable drug target in melanoma. C1 Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Boston Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Program Med Oncol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02129 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. EM david_fisher@dfci.harvard.edu FU NIAMS NIH HHS [AR43369] NR 32 TC 227 Z9 231 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2004 VL 6 IS 6 BP 565 EP 576 DI 10.1016/j.ccr.2004.10.014 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 884HX UT WOS:000226076600007 PM 15607961 ER PT J AU Huntly, BJP Shigematsu, H Deguchi, K Lee, BH Mizuno, S Duclos, N Rowan, R Amaral, S Curley, D Williams, IR Akashi, K Gilliland, DG AF Huntly, BJP Shigematsu, H Deguchi, K Lee, BH Mizuno, S Duclos, N Rowan, R Amaral, S Curley, D Williams, IR Akashi, K Gilliland, DG TI MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CYTOGENETICALLY ABERRANT CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; SELF-RENEWAL; BRAIN-TUMORS; IN-VITRO; AML1-ETO; TRANSFORMATION; FUSION; CANCER AB To better understand the origin of leukemic stem cells, we tested the hypothesis that all leukemia oncogenes could transform committed myeloid progenitor cells lacking the capacity for self-renewal, as has recently been reported for MLL-ENL. Flow-sorted populations of common myeloid progenitors and granulocyte-monocyte progenitors were transduced with the oncogenes MOZ-TIF2 and BCR-ABL, respectively. MOZ-TIF2-transduced progenitors could be serially replated in methylcellulose cultures and continuously propagated in liquid culture, and resulted in an acute myeloid leukemia in vivo that could be serially transplanted. In contrast, BCR-ABL transduction conferred none of these properties to hematopoietic progenitors. These data demonstrate that some, but not all, leukemia oncogenes can confer properties of leukemic stem cells to hematopoietic progenitors destined to undergo apoptotic cell death. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Huntly, BJP (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. EM bhuntly@rics.bwh.harvard.edu; ggilliland@rics.bwh.harvard.edu RI Williams, Ifor/D-3648-2011; huntly, brian/E-6725-2014 OI Williams, Ifor/0000-0002-8810-2911; huntly, brian/0000-0003-0312-161X FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654] NR 43 TC 445 Z9 459 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2004 VL 6 IS 6 BP 587 EP 596 DI 10.1016/j.ccr.2004.10.015 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 884HX UT WOS:000226076600009 PM 15607963 ER PT J AU Ozanne, EM Esserman, LJ AF Ozanne, EM Esserman, LJ TI Evaluation of breast cancer risk assessment techniques: A cost-effectiveness analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; TAMOXIFEN CHEMOPREVENTION; SCREENING STRATEGIES; ABNORMAL-CYTOLOGY; WOMEN; PREVENTION; DISEASE; MODEL; TRIAL AB Objective: Assess the effectiveness and cost-effectiveness of using biomarkers and risk assessment tools to stratify women for breast cancer preventive interventions. Methods: A Markov model was developed to compare risk management strategies for high-risk women considering chemoprevention. Annual screening is compared to the use of chemoprevention for all women and the use of risk assessment technologies to stratify patients for chemoprevention. The biomarker atypia was used to stratify women by risk. Random fine-needle aspiration (rFNA) and ductal lavage (DL) were evaluated and compared as the risk assessment tools used to discover atypia. Sensitivity analyses explore assumptions regarding the prognostic and predictive characteristics of atypia, both the relative breast cancer risk and benefit from chemoprevention women with atypia incur. Results: Risk assessment strategies using rFNA or DL in combination with chemoprevention are found to be cost-effective (<$50,000 per life year saved) in high-risk groups under most scenarios. Both strategies were more effective and less costly in younger cohorts. Effectiveness of the risk assessment strategies increased when higher risk and increased benefit from chemoprevention were associated with atypia. Within the scenarios tested, rFNA is less costly than DL. Conclusion: rFNA and DL appear to be cost-effective in high-risk women, assuming women with detected atypia choose tamoxifen. The tools are largely effective for women who are not motivated to take tamoxifen but would be if atypia were found. As biomarker risk assessment tools better predict the risk of breast cancer and or benefit of interventions, their cost-effectiveness increases. C1 Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, Ctr Med, Carol Franc Breast Care Ctr, Dept Surg, San Francisco, CA 94143 USA. RP Ozanne, EM (reprint author), Harvard Univ, Sch Med, Inst Technol Assessment, Massachusetts Gen Hosp, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM elissa@mgh-ita.org NR 42 TC 9 Z9 14 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2043 EP 2052 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100010 PM 15598759 ER PT J AU Whittemore, AS Gong, G John, EM McGuire, V Li, FP Ostrow, KL DiCioccio, R Felberg, A West, DW AF Whittemore, AS Gong, G John, EM McGuire, V Li, FP Ostrow, KL DiCioccio, R Felberg, A West, DW TI Prevalence of BRCA1 mutation carriers among US non-Hispanic Whites SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POPULATION-BASED SERIES; BREAST-CANCER; OVARIAN-CANCER; ASHKENAZI JEWS; GENETIC EPIDEMIOLOGY; FAMILY-HISTORY; GERMLINE BRCA1; WOMEN; RISK; DNA AB Data from several countries indicate that 1% to 2% of Ashkenazi Jews carry a pathogenic ancestral mutation of the tumor suppressor gene BRCA1. However, the prevalence of BRCA1 mutations among non-Ashkenazi Whites is uncertain. We estimated mutation carrier prevalence in U.S. non-Hispanic Whites, specific for Ashkenazi status, using data from two population-based series of San Francisco Bay Area patients with invasive cancers of the breast or ovary, and data on breast and ovarian cancer risks in Ashkenazi and non-Ashkenazi carriers. Assuming that 90% of the BRCA1 mutations were detected, we estimate a carrier prevalence of 0.24% (95% confidence interval, 0.15-0.39%) in non-Ashkenazi Whites, and 1.2% (95% confidence interval, 0.5-2.6%) in Ashkenazim. When combined with U.S. White census counts, these prevalence estimates suggest that approximately 550,513 U.S. Whites (506,206 non-Ashkenazim and 44,307 Ashkenazim) carry germ line BRCA1 mutations. These estimates may be useful in guiding resource allocation for genetic testing and genetic counseling and in planning preventive interventions. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94503 USA. No Calif Canc Ctr, Union City, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. RP Whittemore, AS (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Redwood Bldg,Room T204, Stanford, CA 94503 USA. EM alicesw@stanford.edu FU NCI NIH HHS [CA16056, CA69417, CA71966, CA78564, CA94069, U01 CA069417, U01 CA069417-10] NR 28 TC 45 Z9 45 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2078 EP 2083 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100015 PM 15598764 ER PT J AU Ziv, E Tice, J Smith-Bindman, R Shepherd, J Cummings, S Kerlikowske, K AF Ziv, E Tice, J Smith-Bindman, R Shepherd, J Cummings, S Kerlikowske, K TI Mammographic density and estrogen receptor status of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; POSTMENOPAUSAL WOMEN; RISK; TAMOXIFEN; MENOPAUSE; PATTERNS; BRCA1; AGE; MUTATIONS; CARCINOMA AB Background: The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)-positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer. Methods: We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity. Results: Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18). Conclusion: Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94115 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94115 USA. Calif Pacific Med Ctr, Inst Res, San Francisco, CA USA. RP Ziv, E (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM eziv@itsa.ucsf.edu RI Ziv, Elad/L-5396-2014 FU NCI NIH HHS [K22 CA109351, U01CA63740]; NIAMS NIH HHS [K12 AR47659] NR 30 TC 66 Z9 67 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2090 EP 2095 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100017 PM 15598766 ER PT J AU Beer, TM Myrthue, A Garzotto, M O'Hara, MF Chin, R Lowe, BA Montalto, MA Corless, CL Henner, WD AF Beer, TM Myrthue, A Garzotto, M O'Hara, MF Chin, R Lowe, BA Montalto, MA Corless, CL Henner, WD TI Randomized study of high-dose pulse calcitriol or placebo prior to radical prostatectomy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D-RECEPTOR; GROWTH-FACTOR-BETA; PROSTATIC INTRAEPITHELIAL NEOPLASIA; BREAST-CANCER CELLS; MESSENGER-RNA EXPRESSION; C-MYC; 1,25-DIHYDROXYVITAMIN D-3; HUMAN KERATINOCYTES; GENE-EXPRESSION; DOWN-REGULATION AB Background: Cancer chemoprevention trials require enormous resources due to the large numbers of patients and the years of follow-up needed to achieve sufficient statistical power. Examination of candidate prevention agents using biomarkers as surrogate end points has been proposed as a method to rapidly identify promising agents for prevention trials. Treatment of patients with candidate agents prior to scheduled biopsy or surgical resection of malignancy allows for direct examination of the treatment effects on tumor tissue. In this study, we selected this approach to test several hypotheses about the effect of calcitriol (1,25-dihydroxycholecalciferol), the active form of vitamin D, on early-stage human prostate cancer. Methods: After selection of surgical treatment for histologically confirmed adenocarcinoma of the prostate, patients were randomized to either calcitriol 0.5 mug/kg or placebo weekly for 4 weeks. The expression levels of the vitamin D receptor (VDR), proliferating cell nuclear antigen, PTEN (MMAC1/TEP1), c-Myc, transforming growth factor (TGF) beta receptor type II (TGFbeta RII), and Bcl-2 were quantified using immunohistochemistry in the patients' prostate specimens post surgery. Results: Thirty-seven of 39 prostate tumors were evaluable for molecular end points. VDR expression was reduced in patients treated with calcitriol (mean, 75.3% of cells) compared with those that received placebo (mean, 98.6%; P = 0.005). Calcitriol treatment did not result in a statistically significant change in the fraction of cells expressing TGFbeta RII, PTEN, or proliferating cell nuclear antigen. Bcl-2 and c-Myc expression was at the lower limits of detection in both the calcitriol group and the placebo group; therefore, we were unable to determine whether drug treatment induced a significant change in these biomarkers. Conclusions: High-dose calcitriol down-regulates VDR expression in human prostate cancer. Further study is needed to determine the biological consequences of VDR down-regulation in prostate cancer. This study shows that the use of the preprostatectomy model is feasible and can be used to test the effect of candidate chemopreventive agents on prostate cancer. C1 Oregon Hlth Sci Univ, Div Hematol & Med Oncol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Div Urol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth Sci Univ, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd,CR-145, Portland, OR 97239 USA. EM beert@ohsu.edu FU NCI NIH HHS [5R21 CA82504-02]; NCRR NIH HHS [5 M01 RR00334] NR 73 TC 25 Z9 27 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 DEC PY 2004 VL 13 IS 12 BP 2225 EP 2232 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100035 PM 15598784 ER PT J AU Chen, J Kyte, C Chan, W Wetmur, JG Fuchs, CS Giovannucci, E AF Chen, J Kyte, C Chan, W Wetmur, JG Fuchs, CS Giovannucci, E TI Polymorphism in the thymidylate synthase promoter enhancer region and risk of colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; ALCOHOL-DEHYDROGENASE; REPEATED SEQUENCES; RECTAL-CANCER; FOLATE; GENE; METHIONINE; COLON AB Thymidylate synthase (TS), a key one-carbon metabolizing gene, encodes an enzyme that converts dUMP to dTMP, the rate-limiting nucleotide in DNA synthesis. We recently reported that a promoter polymorphism in TS modified the risk of colorectal cancer as well as the survival rate after the disease. To explore whether TS may play an important role in colorectal carcinogenesis early in the multistaged pathogenic pathway, we investigated the relation between the TS promoter polymorphism and risk of colorectal adenoma in a nested case-control study within the prospective Health Professionals Follow-up Study. We ascertained the TS genotype from 373 incident colorectal adenoma cases and 720 control subjects. Although there was no overall association between the TS promoter polymorphism and adenoma risk, we observed a significant TS-alcohol interaction (P for interaction = 0.009); relative to low alcohol consumers with the 2R/2R genotype, those with high alcohol consumption (<30 g/d) were not at elevated risk if they had the 2R/2R genotype [relative risk (RR), 0.80; 95% confidence interval (95% CI), 0.34-1.90], but were at higher risk if they had the 2R/3R genotype (RR, 1.70; 95% CI, 0.87-3.31), and at the highest risk (RR, 3.16; 95% Cl, 1.50-6.63) if they had the 3R/3R genotype. In addition, a significant interaction was observed between the TS promoter polymorphism and the 677C > T polymorphism of methylenetetrahydrofolate reductase (MTHFR; P for interaction = 0.007). These findings lend additional support that one-carbon metabolism is an important process in pathogenesis of colorectal cancer. C1 CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 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, J (reprint author), CUNY Mt Sinai Sch Med, Dept Community & Prevent Med, Box 1043,1 Gustave L Levy Pl, New York, NY 10029 USA. EM jia.chen@mssm.edu FU NCI NIH HHS [CA 55075, CA 81750, CA 87969, CA 42182] NR 24 TC 22 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2004 VL 13 IS 12 BP 2247 EP 2250 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 884IC UT WOS:000226077100038 PM 15598787 ER PT J AU Tsuda, H Birrer, MJ Ito, YM Ohashi, Y Lin, M Lee, C Wong, WH Rao, PH Lau, CC Berkowitz, RS Wong, KK Mok, SC AF Tsuda, H Birrer, MJ Ito, YM Ohashi, Y Lin, M Lee, C Wong, WH Rao, PH Lau, CC Berkowitz, RS Wong, KK Mok, SC TI Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CYTOKERATIN 5/6; AMPLIFICATION; EXPRESSION; ADENOCARCINOMA; CARCINOMAS; TUMORS; MESOTHELIOMA; REVEALS; PLEURA AB We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07 average signal ratio for X-chromosomal genes versus autosomal genes provided a sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP amplified DNA. We used this approach to identify DNA copy number abnormalities in the ovarian cancer cell line OVCA633, which has previously been shown to have 12p amplification. Transcription profiling of OVCA633 was also performed. Two amplified and overexpressed genes located on 12p 11, KRAS2 and LRMP, were identified; these were validated with quantitative real-time PCR. Subsequently, the same approach was used to identify CNAs and gene expression alterations in 11 microdissected serous ovarian adenocarcinoma cases. Validated data revealed amplification and overexpression of ERBB3 and FOS and deletion and underexpression of KRT6 and APXL in more than 50% of the tissue samples. These results show the feasibility of using the cDNA array platform to identify changes in DNA and mRNA copy number simultaneously in microdissected tumor tissues. (C) 2004 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Lab Mol Cytogenet, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Tokyo, Sch Hlth Sci & Nursing, Dept Biostat Epidemiol & Prevent Hlth Sci, Tokyo, Japan. NCI, Biomarkers & Prevent Res Branch, Rockville, MD USA. Osaka City Gen Hosp, Dept Obstet & Gynecol, Osaka, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst,Div Gynceol Oncol,Dept Obst, Brigham & Womens Hosp,Lab Gynecol Oncol, Boston, MA 02115 USA. RP Wong, KK (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, Dept Pediat, Lab Mol Cytogenet, Houston, TX 77030 USA. EM kkwong@txccc.org; scmok@rics.bwh.harvard.edu RI Ito, Yoichi/E-2042-2012; OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [P50CA165009, R33 CA103595, U01 CA86381] NR 29 TC 25 Z9 25 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD DEC PY 2004 VL 155 IS 2 BP 97 EP 107 DI 10.1016/j.cancergencyto.2004.03.002 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 880SY UT WOS:000225810700001 PM 15571795 ER PT J AU Agata, N Nogi, H Milhollen, M Kharbanda, S Kufe, D AF Agata, N Nogi, H Milhollen, M Kharbanda, S Kufe, D TI 2-(8-Hydroxy-6-methoxy-L-oxo-1H-2-benzopyran-3-yl)propionic acid, a small molecule isocoumarin, potentiates dexamethasone-induced apoptosis of human multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID NM-3; PROTEIN AB 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule isocoumarin derivative that has recently entered clinical trials as an orally bioavailable anticancer agent. NM-3 induces lethality of human carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the effects of cytotoxic chemotherapeutic agents. The present studies have evaluated,the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate that NM-3 potentiates dexamethasone-induced killing of both dexamethasone-sensitive MM1.S and dexameth as one-resistant RPMI8226 and U266 MM cells. We show that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3 enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3 apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone-induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and U266 MM cells. These findings indicate that NM-3 may be effective in combination with dexamethasone in the treatment of MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. ILEX Prod Inc, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA100707, CA42802] NR 6 TC 24 Z9 24 U1 1 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 DEC 1 PY 2004 VL 64 IS 23 BP 8512 EP 8516 DI 10.1158/0008-5472.CAN-04-2626 PG 5 WC Oncology SC Oncology GA 874QT UT WOS:000225365600006 PM 15574755 ER PT J AU Catley, L Tai, YT Shringarpure, R Burger, R Son, MT Podar, K Tassone, P Chauhan, D Hideshima, T Denis, L Richardson, P Munshi, NC Anderson, KC AF Catley, L Tai, YT Shringarpure, R Burger, R Son, MT Podar, K Tassone, P Chauhan, D Hideshima, T Denis, L Richardson, P Munshi, NC Anderson, KC TI Proteasomal degradation of topoisomerase I is preceded by c-Jun NH2-terminal kinase activation, fas up-regulation, and poly(ADP-Ribose) polymerase cleavage in SN38-mediated cytotoxicity against multiple myeloma SO CANCER RESEARCH LA English DT Article ID DRUG-INDUCED APOPTOSIS; PROSTATE-CANCER CELLS; DNA-DAMAGING AGENTS; PHASE-II; INHIBITOR PS-341; LEUKEMIA-CELLS; DEFICIENT ACTIVATION; COLORECTAL-CANCER; ANTICANCER DRUGS; KAPPA-B AB Topoisomerase I inhibitors are effective anticancer therapies and have shown activity in hematologic malignancies. Here we show for the first time that SN38, the potent active metabolite of irinotecan, induces c-Jun NH2-terminal kinase activation, Fas up-regulation, and caspase 8-mediated apoptosis in multiple myeloma (MM) cells. Proteasomal degradation of nuclear topoisomerase I has been proposed as a resistance mechanism in solid malignancies. SN38-induced proteasomal degradation of topoisomerase I was observed during SN38-mediated cytotoxicity against MNLIS myeloma cell line but occurred after c-Jun NH2-terminal kinase activation, Fas up-regulation, and poly(ADP-ribose) polymerase cleavage and failed to protect cells from apoptosis. Differential toxicity was observed against MM cells versus bone marrow stromal cells, and SN38 inhibited adhesion-induced up-regulation of MM cell proliferation when MM cells adhere to bone marrow stromal cells. In addition, SN38 directly inhibited constitutive and inducible interleukin 6 and vascular endothelial growth factor secretion by bone marrow stromal cells. Synergy was observed when SN38 was used in combination with doxorubicin, bortezomib, as well as poly(ADP-ribose) polymerase inhibitor NU1025 and Fas-activator CH11. These findings have clinical significance, because identification of downstream apoptotic signaling after topoisomerase I inhibition will both elucidate mechanisms of resistance and optimize future combination chemotherapy against MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. Pfizer Oncol, New London, CT USA. RP Catley, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02215 USA. EM Laurence_Catley@dfci.barvard.edu RI Catley, Laurence/E-5313-2013 NR 50 TC 26 Z9 26 U1 1 U2 12 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 DEC 1 PY 2004 VL 64 IS 23 BP 8746 EP 8753 DI 10.1158/0008-5472.CAN-04-2894 PG 8 WC Oncology SC Oncology GA 874QT UT WOS:000225365600037 PM 15574786 ER PT J AU Settleman, J AF Settleman, J TI Inhibition of mutant EGF receptors by Gefitinib - Targeting an Achilles' heel of lung cancer SO CELL CYCLE LA English DT Article DE Gefitinib; cancer; oncogene addiction; EGF receptor; signal transduction ID MUTATIONS; THERAPY AB Recent reports revealed a strong correlation between the presence of somatic activating mutations in the kinase domain of the EGF receptor in some human lung cancers and a striking clinical response to the selective EGF receptor inhibitor, Gefitinib. These oncogenic receptors exhibit altered signaling properties such that they selectively activate downstream survival pathways on which tumor cells have become dependent. Thus, tumor cells are effectively killed by Gefitinib treatment. In addition, the catalytic function of the mutant receptors exhibits increased sensitivity to Gefitinib, raising the possibility that two distinct consequences of Gefitinib action account for its clinical efficacy. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. Harvard Med Sch, Dept Med, Charlestown, MA USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Mol Therapeut, Charlestown, MA 02129 USA. EM Settleman@helix.mgh.harvard.edu NR 8 TC 13 Z9 13 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD DEC PY 2004 VL 3 IS 12 BP 1496 EP 1497 DI 10.4161/cc.3.12.1325 PG 2 WC Cell Biology SC Cell Biology GA 902SE UT WOS:000227376000007 PM 15539955 ER PT J AU Handy, DE Scolaro, J Chen, J Huang, P Loscalzo, J AF Handy, DE Scolaro, J Chen, J Huang, P Loscalzo, J TI L-arginine increases plasma homocysteine in APOE(-/-)/INOS-/- double knockout mice SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE L-arginine; homocysteine; atherosclerosis; vascular disease; methylation ID NITRIC-OXIDE SYNTHASE; CYSTATHIONINE BETA-SYNTHASE; GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY; DIETARY L-ARGININE; ENDOTHELIAL DYSFUNCTION; ACCELERATES ATHEROSCLEROSIS; CREATINE DEFICIENCY; INBORN ERROR; MURINE MODEL; NO SYNTHASE AB Previous studies have shown that L-arginine (L-Arg) administration to apoE(-/-)/iNOS(-/-) double knockout mice (dKO) on a Western diet paradoxically results in an increase in atherosclerotic lesion size. We hypothesized that the potential beneficial effects of L-Arg could be offset, in pail, by the byproducts of L-Arg catabolism, especially the atherogenic risk factor, homocysteine. In the kidney, L-Arg is converted to L-ornithine and guanidinoacetate (GAA) by L-arginine-glycine amidinotransferase. The efficient transmethylation of GAA by an S-adenosyl-methionine (SAM)-dependent methyltransferase in liver yields creatine and S-adenosyl-homocysteine (SAH), which is readily hydrolyzed to homocysteine and adenosine. We, therefore, measured total plasma homocysteine in the dKO mice and control mice. We found that L-Arg supplementation caused a 37% increase in total plasma homocysteine (tHcy) levels in dKO mice compared to controls not treated with L-Arg (5.2 +/- 2.2 vs 3.8 +/- 1.5 M Hey, p<0.04). In a liver cell fine, HepG2, addition of 10 and 50 muM GAA in the presence of 50 muM L-methionine (L-Met) increased tHcy production by approximately 1.47 (p<0.0001) and 2.3-fold (p<0.0001), respectively. In the presence of additional 100 muM L-Met, baseline homocysteine production was elevated by 20% (p<0.005), and 10 and 50 M GAA augmented homocysteine production by an additional 1.88- (p<0.0001) and 3.4-fold (p<0.001), respectively, compared with 50 muM L-Met. These data suggest that increased concentrations of a methyl acceptor, such as L-Arg-derived GAA, drives SAM-dependent-methylation and consequent homocysteine formation. Furthermore, L-Met levels can also influence homocysteine production likely by regulating the synthesis of the methyl donor SAM. Epidemiological studies have suggested that homocysteine is a graded risk factor. In animal models, modest elevations of homocysteine can cause endothelial dysfunction and augment atherosclerosis. Our data suggest that L-arginine supplementation may contribute to vascular injury and atherogenesis under some circumstances by elevating homocysteine levels. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Loscalzo, J (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 715 Albany St W 507, Boston, MA 02118 USA. EM jloscalz@bu.edu FU NHLBI NIH HHS [N01 HV28178, HL 61759, P01 HL 55993, HL 58976] NR 44 TC 4 Z9 5 U1 0 U2 1 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD DEC PY 2004 VL 50 IS 8 BP 903 EP 909 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 893JA UT WOS:000226713900005 PM 15704254 ER PT J AU Yang, DL Wu, ZW Jiang, SB Luo, ZM AF Yang, DL Wu, ZW Jiang, SB Luo, ZM TI A multiple scattering theory for proton penetration SO CHINESE PHYSICS LETTERS LA English DT Article ID DOSE CALCULATIONS; MONTE-CARLO; RANGE AB We extend the electron small-angle multiple scattering theory to proton penetration. After introducing the concept of narrow energy spectra, the proton energy loss process is included in the proton deep penetration theory. It precisely describes the whole process of proton penetration. Compared to the Monte Carlo method, this method maintains the comparable precision and possesses much higher computational efficiency. Thus, it shows the real feasibility of applying this algorithm to proton clinical radiation therapy. C1 Sichuan Univ, Key Lab Radiat Phys & Technol, Minist Educ, Chengdu 610064, Peoples R China. Sichuan Univ, Key Lab Radiat Phys & Technol, Ctr Radiat Phys, Chengdu 610064, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA. RP Luo, ZM (reprint author), Sichuan Univ, Key Lab Radiat Phys & Technol, Minist Educ, Chengdu 610064, Peoples R China. EM luozm@scu.edu.cn NR 15 TC 2 Z9 4 U1 0 U2 0 PU CHINESE PHYSICAL SOC PI BEIJING PA P O BOX 603, BEIJING 100080, PEOPLES R CHINA SN 0256-307X J9 CHINESE PHYS LETT JI Chin. Phys. Lett. PD DEC PY 2004 VL 21 IS 12 BP 2547 EP 2550 DI 10.1088/0256-307X/21/12/063 PG 4 WC Physics, Multidisciplinary SC Physics GA 880IP UT WOS:000225782500063 ER PT J AU Yang, WH Yu, JH Nakajima, A Neuberg, D Lindor, K Bloch, DB AF Yang, Wei-Hong Yu, Jiang Hong Nakajima, Ayako Neuberg, Donna Lindor, Keith Bloch, Donald B. TI Do Antinuclear Antibodies in Primary Biliary Cirrhosis Patients Identify Increased Risk for Liver Failure? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease with a variable clinical course. Identification of serologic markers associated with increased risk of liver failure would assist in management of PBC patients. The objective of this study was to identify antinuclear antibody (ANA) markers that may be used to predict PBC outcome. Methods: Indirect immunofluorescence was used to identify ANAs in 492 PBC patients. chi(2) and Kaplan-Meier analyses were used to examine the association between ANAs and liver failure. Results: A greater percentage of ANA-positive, compared to ANA-negative, PBC patients developed liver failure (41% vs 25%, P = .005). The presence of anti-centromere antibodies was associated with liver failure (anti-centromere antibody positive vs negative, 58% vs 33%, P = .001). The time to liver failure was shorter in ANA-positive, compared with ANA-negative, patients (log rank score 5.8, P = .02). After 8.9 years (the median follow-up for patients without liver failure), 68% of ANA-positive and 81% of ANA-negative patients were free of liver failure. Anti-centromere antibodies were also associated with a shorter time to liver failure (log rank score 8.4, P = .004). After 8.9 years, 52% of anti-centromere antibody positive and 74% of anti-centromere antibody negative patients were without liver failure. Conclusions: ANAs in general, and anti-centromere antibodies in particular, are associated with liver failure in PBC. PBC patients with ANAs may be candidates for treatment with experimental therapies to prolong the interval between diagnosis and liver failure. ANA-negative patients, who appear to have a relatively benign clinical course, should perhaps be treated with ursodeoxycholic acid alone. C1 [Yang, Wei-Hong; Yu, Jiang Hong; Nakajima, Ayako; Bloch, Donald B.] Massachusetts Gen Hosp, Gen Med Serv, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Yang, Wei-Hong; Yu, Jiang Hong; Nakajima, Ayako; Neuberg, Donna; Bloch, Donald B.] Harvard Univ, Sch Med, Boston, MA USA. [Lindor, Keith] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp E, CNY 149 13th St, Charlestown, MA 02129 USA. EM bloch@helix.mgh.harvard.edu FU Arthritis Foundation; National Institutes of Health [DK-051179]; Harvard Clinical Nutrition Center [DK-40561]; American Heart Association FX Supported by grants from the Arthritis Foundation, the National Institutes of Health (DK-051179), and a pilot grant from the Harvard Clinical Nutrition Center (DK-40561). D. B. Bloch is a recipient of an Established Investigator Grant from the American Heart Association. NR 27 TC 49 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD DEC PY 2004 VL 2 IS 12 BP 1116 EP 1122 DI 10.1053/S1542-3565(04)00465-3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KX UT WOS:000208072400013 PM 15625657 ER PT J AU Koido, S Ohana, M Liu, CL Nikrui, N Durfee, J Lerner, A Gong, JL AF Koido, S Ohana, M Liu, CL Nikrui, N Durfee, J Lerner, A Gong, JL TI Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation SO CLINICAL IMMUNOLOGY LA English DT Article DE DC-breast or ovarian cancer cell fusion; antigen presentation; T cell activation; ultrastructural characterization ID ANTITUMOR IMMUNITY; CARCINOMA-CELLS; IN-VITRO; BREAST-CARCINOMA; FUSION CELLS; VACCINATION; LYMPHOCYTES; INDUCTION; MICE; IMMUNIZATION AB Fusion of human dendritic cells (DC) with tumor cells is an effective approach for delivering tumor antigens to DC, and DC/tumor fusion cells are potent stimulators of autologous T cells. However, the integration and morphology of DC/tumor fusion cells has not been examined. In the present study, we fused patient-derived DC to autologous breast or ovarian carcinoma cells. The fusion cells possessed the properties of both parent cells. After fusion, the cytoplasm of the two cells was integrated, whereas their nuclei remained separate entities. Colocalization of MUC1 peptide and HLA-DR molecules was observed on fusion cells under the immunoelectron microscope. Coculture of patient-derived peripheral blood mononuclear cells (PBMC) with DC/tumor fusion cells resulted in activation of CD4 and CD8 T cells as assessed by IFN-gamma secretion, HLA-A*0201-MUC1 tetramer, and standard cytotoxic T lymphocyte (CTL) assays. The present study provides first evidence of integration of human DC and tumor cells and links their properties to T cell activation. (C) 2004 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 650 Albany St,X309, Boston, MA 02118 USA. EM jgong@bu.edu FU NCI NIH HHS [R01 CA87057] NR 28 TC 48 Z9 56 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD DEC PY 2004 VL 113 IS 3 BP 261 EP 269 DI 10.1016/j.clim.2004.08.004 PG 9 WC Immunology SC Immunology GA 869ID UT WOS:000224975700008 PM 15507391 ER PT J AU Drappatz, J Batchelor, T AF Drappatz, J Batchelor, T TI Neurologic complications of plasma cell disorders SO CLINICAL LYMPHOMA LA English DT Review DE cord compression; epidural disease; hypercalcemia; hyperviscosity syndrome; leptomeningeal disease; peripheral neuropathy ID SPINAL-CORD COMPRESSION; CENTRAL-NERVOUS-SYSTEM; INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; MYELIN-ASSOCIATED GLYCOPROTEIN; BING-NEEL-SYNDROME; IGM MONOCLONAL GAMMOPATHY; MYELOMA BONE-DISEASE; MOTOR-NEURON DISEASE; MULTIPLE-MYELOMA; PERIPHERAL NEUROPATHY AB Plasma cell disorders are associated with a wide spectrum of neurologic complications that predominantly involve the peripheral nervous system. Distinct clinical syndromes have been recognized, and antibodies to several glycoproteins of the peripheral nervous system have been identified. The main clinical, laboratory, immunologic, and pathologic features of neurologic complications that occur in patients with monoclonal gammopathies of unknown significance, multiple myeloma, plasmacytoma, plasma cell leukemia, Waldenstrom's macroglobulinemia, and immunoglobulin-related amyloidosis are summarized in this review. Knowledge of the pathogenesis in this group of disorders has increased in recent years, allowing better diagnosis and treatment. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, 100 Blossom St,Cox 315, Boston, MA 02114 USA. EM tbatchelor@partners.org NR 106 TC 14 Z9 14 U1 1 U2 2 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD DEC PY 2004 VL 5 IS 3 BP 163 EP 171 DI 10.3816/CLM.2004.n.022 PG 9 WC Oncology SC Oncology GA 884TJ UT WOS:000226109000008 PM 15636691 ER PT J AU Treon, SP Tournilhac, O Branagan, AR Hunter, Z Xu, L Hatjiharissi, E Santos, DD AF Treon, SP Tournilhac, O Branagan, AR Hunter, Z Xu, L Hatjiharissi, E Santos, DD TI Clinical responses to sildenafil in Waldenstrom's macroglobulinemia SO CLINICAL LYMPHOMA LA English DT Article DE apoptosis; lymphoplasmacytic lymphoma; phosphodiesterase inhibitor ID CONSENSUS PANEL RECOMMENDATIONS; CHRONIC LYMPHOCYTIC-LEUKEMIA; 2ND INTERNATIONAL WORKSHOP; APOPTOSIS AB Waldenstrom's macroglobulinemia (WM) is an incurable B-cell malignancy. Interestingly, an unusual response activity was observed in 5 patients with WM that appeared related to their use of sildenafil, a phosphodiesterase inhibitor used to treat erectile dysfunction. One patient demonstrated a complete remission, and 4 other patients demonstrated less dramatic, but also unexpected, responses associated with sildenafil. In view of these findings, WM tumor cells were culture-sorted with sildenafil at pharmacologically achievable levels and apoptosis was demonstrated in tumor cells from all 5 patients. These studies suggest that sildenafil may be an active agent in the treatment of WM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, 44 Binney St,nLG102, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; OI Hunter, Zachary/0000-0002-1689-1691; Branagan, Andrew/0000-0002-3868-9267 NR 5 TC 12 Z9 12 U1 0 U2 4 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD DEC PY 2004 VL 5 IS 3 BP 205 EP 207 DI 10.3816/CLM.2004.n.029 PG 3 WC Oncology SC Oncology GA 884TJ UT WOS:000226109000016 PM 15636699 ER PT J AU Harris, WH AF Harris, WH TI Presidential Guest Addess - Conquest of a Worldwide Human Disease - Particle-induced periprosthetic osteolysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Hip-Society 2004 Meeting CY MAR 13, 2004 CL San Francisco, CA SP Hip Soc ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; SYNOVIAL-LIKE MEMBRANE; BONE-CEMENT INTERFACE; FOLLOW-UP; WEAR; REPLACEMENTS; COMPONENTS; PROSTHESES AB It is rare in the long history of human disease to encounter a completely unique disease. In the 21st century, when it does occur, the disease commonly is man-made, as is true for periprosthetic osteolysis. However, it also is rare to unravel the mysteries of a biologic process as complex as periprosthetic osteolysis in slightly longer than one generation and even less common to create the means for the worldwide prevention of an entire disease. Such is the story of periprosthetic osteolysis. The adventure from the iatrogenic creation of the disease to the identification of its pathology, to the understanding of its molecular biology and, subsequently, to its prevention, during a period of four decades, is a fascinating story of medical detective work. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM wharris.obbl@partners.org NR 30 TC 33 Z9 37 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2004 IS 429 BP 39 EP 42 DI 10.1097/01.blo.0000149821.72760.39 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 877EF UT WOS:000225549900006 PM 15577463 ER PT J AU Harris, WH AF Harris, WH TI Highly cross-linked, electron-beam-irradiated, melted polyethylene - Some pros SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Hip-Society 2004 Meeting CY MAR 13, 2004 CL San Francisco, CA SP Hip Soc ID TOTAL HIP-ARTHROPLASTY; MOLECULAR-WEIGHT POLYETHYLENE; SWING PHASE MICROSEPARATION; LOW-FRICTION ARTHROPLASTY; CERAMIC BEARING SURFACES; WEAR RATES; REPLACEMENT; ASSOCIATION; LARGER AB Extensive new evidence generated within the past the year provides strong support for the use of electron-beam highly cross-linked, subsequently melted ultra-high molecular weight polyethylene in total hip replacement arthroplasty. In terms of wear reduction, three studies involving three different demographic groups and two different measurement techniques have found that the femoral head penetration with this type of polyethylene after bedding in has finished taking place is less than 10 micra per year. This wear rate is similar to the wear rate of metal-on-metal and ceramic-on-ceramic articulations. Retrieval specimens up to 3 years after insertion confirmed the minimal wear by exhibiting persisting machine marks throughout the inside diameter of the liner. Extensive studies show no evidence of oxidation, confirming the absence of residual free radicals. No evidence of fatigue failure exists except three known cases out of 150,000, in which malposition of the acetabular component produced abnormally high contact stresses on unsupported polyethylene. The in vivo wear, oxidation resistance, and mechanical properties of this alternative bearing material are excellent, with in vivo durations now exceeding five years. The other major advantages over hard-on-hard bearings including familiarity, adaptability, forgiveness, and cost seem to be compelling. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM wharris.obbl@partners.org NR 38 TC 14 Z9 16 U1 0 U2 3 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 DEC PY 2004 IS 429 BP 63 EP 67 DI 10.1097/01.blo.0000149827.55160.42 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 877EF UT WOS:000225549900010 PM 15577467 ER PT J AU Mankin, HJ Hornicek, FI Rosenberg, AE Harmon, DC Gebhardt, MC AF Mankin, HJ Hornicek, FI Rosenberg, AE Harmon, DC Gebhardt, MC TI Survival data for 648 patients with osteosarcoma treated at one institution SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ROTHMUND-THOMSON-SYNDROME; HIGH-GRADE OSTEOSARCOMA; OSTEOGENIC-SARCOMA; NEOADJUVANT CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; P-GLYCOPROTEIN; PREOPERATIVE CHEMOTHERAPY; CURRENT MANAGEMENT; PROGNOSTIC-FACTORS; DELAYED SURGERY AB During the past 30 years, the orthopaedic oncology group at the Massachusetts General Hospital has treated 648 patients with osteosarcoma centrally located in the bone. Using records maintained in a specifically designed computer system, a study was done to assess the factors that seemed to influence the survival outcome. The overall survival for the entire series was 68% at an average followup of 6+/-4 years. Death occurred at a mean of 3+/-3 years. Patient gender had no effect, but age of the patient was correlated with survival data, with the poorest survival for the older patients. Surgical treatment had no effect on outcome, but the Musculoskeletal Tumor Society stage of the lesion, the presence of metastases or local recurrence, and the chemotherapeutic treatment (very dependent on the drugs available and adjuvant versus neoadjuvant administration at various decades) all had a profound effect. In addition, anatomic location, size of the tumor, and percentage of tumor cells killed after neoadjuvant chemotherapy all had an effect on outcome. C1 Harvard Univ, Dept Orthopaed Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Med Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Dept Orthopaed Oncol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hmankin@partners.org NR 82 TC 91 Z9 96 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 DEC PY 2004 IS 429 BP 286 EP 291 DI 10.1097/01.blo.0000145991.65770.e6 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 877EF UT WOS:000225549900043 PM 15577500 ER PT J AU Doornberg, J Ring, D Jupiter, JB AF Doornberg, J Ring, D Jupiter, JB TI Effective treatment of fracture-dislocations of the olecranon requires a stable trochlear notch SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MONTEGGIA FRACTURES; RADIAL HEAD; ELBOW; ADULTS; CLASSIFICATION; MANAGEMENT; ULNA AB Our goal with this study was to better define and characterize fracture-dislocations of the olecranon and to provide additional data regarding complications and elbow function after operative treatment. Twenty-six patients with fracture-dislocations of the elbow were reviewed retrospectively. Ten had anterior and 16 had posterior fracture-dislocations. Five of 10 patients with anterior injuries and all of the patients with posterior injuries had an associated fracture of the coronoid process of the ulna. One of 10 patients with anterior and 13 of 16 patients with posterior injuries had fracture of the radial head. Only one patient had a true dislocation of the ulnohumeral joint. In the other 25 patients the articular surfaces remained apposed. All 26 patients were treated operatively and followed up for at least 3 years (average, 6 years). The results were good or excellent in 21 of 26 patients according to the system of Broberg and Morrey. The five unsatisfactory results were related to inadequate fixation of the coronoid with subsequent arthrosis (three patients), proximal radioulnar synostosis (three patients), and a subsequent fracture of the distal humerus (one patient). Fracture-dislocations of the olecranon occur in anterior and posterior patterns with specific injury characteristics and pitfalls. The key to effective treatment is stable restoration of the trochlear notch. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Hand & Upper Extrem Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA. EM dring@partners.org NR 24 TC 37 Z9 44 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 DEC PY 2004 IS 429 BP 292 EP 300 DI 10.1097/01.blo.0000142627.28396.cb PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 877EF UT WOS:000225549900044 PM 15577501 ER PT J AU Morris, TL Hirshfeld-Becker, DR Henin, A Storch, EA AF Morris, TL Hirshfeld-Becker, DR Henin, A Storch, EA TI Developmentally sensitive assessment of social anxiety SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article; Proceedings Paper CT Meeting on Current Issues and Ideas in Anxiety Disorders in Children and Adolescents CY NOV, 2001 CL Philadelphia, PA ID TEST-RETEST RELIABILITY; DIAGNOSTIC INTERVIEW SCHEDULE; STRUCTURED PSYCHIATRIC INTERVIEW; REPORTED BEHAVIORAL-INHIBITION; RANDOMIZED CLINICAL-TRIAL; PARENT-CHILD AGREEMENT; SCHOOL-AGE-CHILDREN; EMOTIONAL DISORDERS; MATERNAL DEPRESSION; PANIC DISORDER AB Social anxiety affects children across the developmental spectrum. Early-onset social phobia may be particularly impairing because of its disruptive effects on social and academic functioning during a child's formative years and because of the elevated risks of childhood adversity in anxious individuals. Unfortunately, little attention has been paid to the early identification and assessment of social anxiety in young children. The ability to recognize and monitor or remediate social anxiety early in development would be of great advantage in reversing this potentially debilitating course. This article reviews various methods available to assess social anxiety and associated conditions. Particular emphasis is placed on the description and assessment of behavioral inhibition in infants and very young children as an early marker or precursor to the development of social anxiety. For school-aged children and adolescents, a greater range of assessment options is available including behavioral observation, clinician ratings, child self-report questionnaires, and parent and peer reports. In an effort to advance our understanding of the developmental psychopathology of social anxiety, further research is necessary to determine the equivalency of various assessment strategies across developmental periods. C1 W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Univ Florida, Gainesville, FL 32611 USA. RP Morris, TL (reprint author), W Virginia Univ, Dept Psychol, 1124 Life Sci Bldg,53 Campus Dr, Morgantown, WV 26506 USA. EM tracy.morris@mail.wvu.edu RI Storch, Eric/I-4935-2012; OI Morris, Tracy/0000-0002-4257-7989 NR 173 TC 17 Z9 17 U1 5 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD WIN PY 2004 VL 11 IS 1 BP 13 EP 28 DI 10.1016/S1077-7229(04)80004-X PG 16 WC Psychology, Clinical SC Psychology GA 916WO UT WOS:000228417500003 ER PT J AU Klein, I Dubois, J Mangin, JF Kherif, F Flandin, G Poline, JB Denis, M Kosslyn, SM Le Bihan, D AF Klein, I Dubois, J Mangin, JF Kherif, F Flandin, G Poline, JB Denis, M Kosslyn, SM Le Bihan, D TI Retinotopic organization of visual mental images as revealed by functional magnetic resonance imaging SO COGNITIVE BRAIN RESEARCH LA English DT Article DE mental imagery; retinotopy; visual cortex; fMRI ID CORTEX V1; ACTIVATION; FMRI; AREAS; PET; CONNECTIONS; GENERATION; STRIATE; ANATOMY; HUMANS AB In this study, we used event-related functional magnetic resonance imaging to investigate whether visual mental images retinotopically activate early visual cortex. Six participants were instructed to visualize or view horizontally or vertically oriented flashing bow-tie shaped stimuli. When compared to baseline, imagery globally activated Area V1. When the activation evoked by the stimuli at the different orientations was directly compared, distinct spatial activation patterns were obtained for each orientation in most participants. Not only was the topography of the activation patterns from imagery similar to the topography obtained with a corresponding visual perception task, but it closely matched the individual cortical representation of either the horizontal or the vertical visual field meridians. These findings strongly support that visual imagery and perception share low-level anatomical substrate and functional processes. Binding of spatial features is suggested as one possible mechanism. (C) 2004 Elsevier B.V. All rights reserved. C1 CEA, DRM, DSV, SHF,Anat & Funct Neuroimaging Lab, F-91401 Orsay, France. CNRS, Grp Cognit Humaine, LIMSI, F-91403 Orsay, France. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Le Bihan, D (reprint author), CEA, DRM, DSV, SHF,Anat & Funct Neuroimaging Lab, 4 Pl Gen Leclerc, F-91401 Orsay, France. EM lebihan@shfj.cea.fr RI Dubois, Jessica/P-2461-2014 OI Dubois, Jessica/0000-0003-4865-8111 NR 31 TC 30 Z9 31 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD DEC PY 2004 VL 22 IS 1 BP 26 EP 31 DI 10.1016/j.cogbrainres.2004.07.006 PG 6 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 881VU UT WOS:000225898300003 ER PT J AU Friedman, ES Thase, ME Kornblith, SJ Wisniewski, SR Briggs, MM Rush, AJ Carmin, C Hollon, SD Petersen, T Veenstra, G AF Friedman, ES Thase, ME Kornblith, SJ Wisniewski, SR Briggs, MM Rush, AJ Carmin, C Hollon, SD Petersen, T Veenstra, G TI The implementation of cognitive therapy in STAR*D SO COGNITIVE THERAPY AND RESEARCH LA English DT Article DE cognitive behavior therapy; major depression; STAR*D study; implementation; quality ID MAJOR DEPRESSIVE DISORDER; NATIONAL-COMORBIDITY-SURVEY; CONTROLLED-TRIAL; PRIMARY-CARE; PSYCHOTHERAPY; PREVENTION; EFFICACY AB The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project will provide symptomatic and functional outcome data to evaluate the theoretical principles and clinical beliefs that currently guide the treatment of nonpsychotic major depression. Cognitive Therapy (CT) for depression has been chosen as a switch or augmentation treatment for patients who have failed an adequate trial of the antidepressant citalopram. We describe the rationale, organization, and role of CT in STAR*D. We discuss the issues involved in developing and implementing CT in a large, multisite, effectiveness study: therapist selection, training, certification, quality assurance, and post-training supervision. We conclude with a discussion of the implications of our implementation procedures on interpreting the results of the STAR*D study. C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Univ Texas, Dallas, TX 75230 USA. Univ Illinois, Chicago, IL USA. Vanderbilt Univ, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Kansas, Wichita, KS 67214 USA. RP Friedman, ES (reprint author), Univ Pittsburgh, Pittsburgh, PA 15213 USA. EM friedmane@upmc.edu RI Carmin, Cheryl/F-8004-2014; OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 NR 30 TC 4 Z9 4 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 DEC PY 2004 VL 28 IS 6 BP 819 EP 833 DI 10.1007/s10608-004-0668-1 PG 15 WC Psychology, Clinical SC Psychology GA 894QW UT WOS:000226807700007 ER PT J AU Napadow, V Liu, J Kaptchuk, TJ AF Napadow, V Liu, J Kaptchuk, TJ TI A systematic study of acupuncture practice: acupoint usage in an outpatient setting in Beijing, China SO COMPLEMENTARY THERAPIES IN MEDICINE LA English DT Article DE acupuncture treatment; alternative and integrative medicine; acupoint; Chinese medicine ID LOW-BACK-PAIN; DIAGNOSIS; PATIENT AB Acupuncture textbooks mention a wide assortment of indications for each acupuncture point and, conversely, each disease or indication can be treated by a wide assortment of acupoints. However, little systematic information exists on how acupuncture is actually used in practice: i.e. which points are actually selected and for which conditions. This study prospectively gathered data on acupuncture point usage in two primarily acupuncture hospital clinics in Beijing, China. Of the more than 150 unique acupoints, the 30 most commonly used points represented 68% of the total number of acupoints needled at the first clinic, and 63% of points needled at the second clinic. White acupuncturists use a similar set of most prevalent points, such as LI-4 (used in >65% of treatments at both clinic sites), this core of points only partially overlaps. These results support the hypothesis that while the most commonly used points are similar from one acupuncturist to another, each practitioner tends to have certain acupoints, which are favorites as core points or to round out the point prescription. In addition, the results of this study are consistent with the recent development of "manualized" protocols in randomized controlled trials of acupuncture where a fixed set of acupoints are augmented depending on individualized signs and symptoms (TCM patterns). (C) 2004 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Athinoula A Martinos Imaging Ctr, Boston, MA 02114 USA. Logan Coll Chiroprac, Dept Radiol, Chesterfield, MO USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA 02115 USA. RP Napadow, V (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Imaging Ctr, Boston, MA 02114 USA. FU NCCIH NIH HHS [P01 AT002048-A-01, R01AT001414, K01 AT02166-01] NR 14 TC 14 Z9 14 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0965-2299 J9 COMPLEMENT THER MED JI Complement. Ther. Med. PD DEC PY 2004 VL 12 IS 4 BP 209 EP 216 DI 10.1016/j.ctim.2004.10.001 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 893JN UT WOS:000226715200004 PM 15649834 ER PT J AU Becker, AE AF Becker, AE TI New global perspectives on eating disorders SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Editorial Material ID ANOREXIA-NERVOSA; ETHNIC-GROUPS; ATTITUDES; BEHAVIORS; DISTURBANCES; GIRLS C1 Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Adult Eating & Weight Disorders Program, Boston, MA 02114 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu NR 20 TC 7 Z9 9 U1 2 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD DEC PY 2004 VL 28 IS 4 BP 433 EP 437 DI 10.1007/s11013-004-1063-9 PG 5 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 913ZQ UT WOS:000228194600001 PM 15847049 ER PT J AU Becker, A AF Becker, A TI Television, disordered eating, and young women in Fiji: Negotiating body image and identity during rapid social change SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE body image; eating disorders; Fiji; modernization ID ANOREXIA-NERVOSA; MEDIA; VIOLENCE; ADOLESCENTS; IMPACT; SELF; AMERICAN; THINNESS; BEHAVIOR; BULIMIA AB Although the relationship between media exposure and risk behavior among youth is established at a population level, the specific psychological and social mechanisms mediating the adverse effects of media on youth remain poorly understood. This study reports on an investigation of the impact of the introduction of television to a rural community in Western Fiji on adolescent ethnic Fijian girls in a setting of rapid social and economic change. Narrative data were collected from 30 purposively selected ethnic Fijian secondary school girls via semi-structured, open-ended interviews. Interviews were conducted in 1998, 3 years after television was first broadcast to this region of Fiji. Narrative data were analyzed for content relating to response to television and mechanisms that mediate self and body image in Fijian adolescents. Data in this sample suggest that media imagery is used in both creative and destructive ways by adolescent Fijian girls to navigate opportunities and conflicts posed by the rapidly changing social environment. Study respondents indicated their explicit modeling of the perceived positive attributes of characters presented in television dramas, but also the beginnings of weight and body shape preoccupation, purging behavior to control weight, and body disparagement. Response to television appeared to be shaped by a desire for competitive social positioning during a period of rapid social transition. Understanding vulnerability to images and values imported with media will be critical to preventing disordered eating and, potentially, other youth risk behaviors in this population, as well as other populations at risk. C1 Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Adult Eating & Weight Disorders Program, Boston, MA 02114 USA. RP Becker, A (reprint author), Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu NR 57 TC 89 Z9 89 U1 9 U2 39 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD DEC PY 2004 VL 28 IS 4 BP 533 EP 559 DI 10.1007/s11013-004-1067-5 PG 27 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 913ZQ UT WOS:000228194600005 PM 15847053 ER PT J AU Oehmig, A Fraefel, C Breakefield, XO Ackermann, M AF Oehmig, A Fraefel, C Breakefield, XO Ackermann, M TI Herpes simplex virus type 1 amplicons and their hybrid virus partners, EBV, AAV, and retrovirus SO CURRENT GENE THERAPY LA English DT Review DE herpes simplex virus type 1; Epstein-Barr virus; adeno-associated virus; retrovirus; vector systems; amplicon; hybrid amplicon ID EPSTEIN-BARR-VIRUS; SITE-SPECIFIC INTEGRATION; RECOMBINANT ADENOASSOCIATED VIRUS; ADENO-ASSOCIATED VIRUS; MEDIATED GENE-TRANSFER; TO-CELL SPREAD; BACTERIAL ARTIFICIAL CHROMOSOME; POSITRON-EMISSION-TOMOGRAPHY; HEPARAN-SULFATE PROTEOGLYCAN; CRE-LOXP RECOMBINATION AB HSV-1 amplicons can accommodate foreign DNA of any size up to 150 kbp. Genomic sequences as well as cDNA, large transcriptional regulatory sequences for cell type-specific expression, or multiple transgenes can be inserted in a modular fashion. HSV-1 amplicon vectors deliver DNA efficiently into the cell nucleus as an extrachromosomal, non-replicating circular concatenate, which is rapidly diluted, at least in dividing cells. Consequently, transgene expression is lost within days to weeks in dividing cells, but may be retained for months in non-dividing cells. In contrast, vectors based on Epstein-Barr virus, adeno-associated virus, or retroviruses can mediate long-term transgene expression, as vector DNA is retained by episomal replication or chromosomal integration. Hybrid amplicons use genetic elements from HSV-1 that allow replication and packaging of the vector DNA into HSV-1 virions, thereby conserving the large transgene capacity of HSV-1, and genetic elements from other viruses that confer genetic stability to the vector DNA within transduced cells. Additional strategies to sustain genetic material in infected cells include the incorporation of recombinases from different bacteriophages or transposable elements of the Tcl/mariner family in the amplicon vector. Moreover, modification of the HSV-1 virion itself offers a myriad of possibilities to improve gene delivery by targeting specific cell populations or transporting foreign proteins, such as Cre recombinase or the adeno-associated virus Rep protein, which can control the fate and expression of the therapeutic transgene. C1 Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Fraefel, C (reprint author), Univ Zurich, Inst Virol, Winterthurerstr 266A, CH-8057 Zurich, Switzerland. EM cornelf@vetvir.unizh.ch NR 222 TC 29 Z9 32 U1 3 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD DEC PY 2004 VL 4 IS 4 BP 385 EP 408 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA 871RP UT WOS:000225151300004 PM 15578989 ER PT J AU West, JA Daley, GQ AF West, JA Daley, GQ TI In vitro gametogenesis from embryonic stem cells SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID PRIMORDIAL GERM-CELLS; MOUSE EMBRYO; DERIVATION; LINE; SPERMATOGENESIS; DIFFERENTIATION; TRANSPLANTATION; SPECIFICATION; CULTURE; MICE AB Many insights into mammalian germ cell development have been gained through genetic engineering and in vivo studies, but the lack of an in vitro system for deriving germ cells has hindered potential advances in germ cell biology. Recent studies have demonstrated embryonic stem cell differentiation into germ cells and more mature gametes, although significant unanswered questions remain about the functionality of these cells. The derivation of germ cells from embryonic stem cells in vitro provides an invaluable assay both for the genetic dissection of germ cell development and for epigenetic reprogramming, and may one day facilitate nuclear transfer technology and infertility treatments. C1 Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP West, JA (reprint author), Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. RI West, Jason/I-4445-2014 OI West, Jason/0000-0002-7252-8651 FU NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 37 TC 18 Z9 20 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD DEC PY 2004 VL 16 IS 6 BP 688 EP 692 DI 10.1016/j.ceb.2004.09.006 PG 5 WC Cell Biology SC Cell Biology GA 874YY UT WOS:000225387800014 PM 15530782 ER PT J AU Hanczyc, MM Szostak, JW AF Hanczyc, MM Szostak, JW TI Replicating vesicles as models of primitive cell growth and division SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID FATTY-ACID VESICLES; GIANT LIPOSOMES; TRANSFORMATION; MICROSCOPY; FUSION; SYSTEM AB Primitive cells, lacking the complex bio-machinery present in modern cells, would have had to rely on the self-organizing properties of their components and on interactions with their environment to achieve basic cellular functions such as growth and division. Many bilayer-membrane vesicles, depending on their composition and environment, can exhibit complex morphological changes such as growth, fusion, fission, budding, internal vesicle assembly and vesicle-surface interactions. The rich dynamic properties of these vesicles provide interesting models of how primitive cellular replication might have occurred in response to purely physical and chemical forces. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@moibio.mgh.harvard.edu OI Hanczyc, Martin/0000-0002-5453-2139 NR 19 TC 103 Z9 107 U1 10 U2 44 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 DEC PY 2004 VL 8 IS 6 BP 660 EP 664 DI 10.1016/j.cbpa.2004.10.002 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 880IN UT WOS:000225782300015 PM 15556412 ER PT J AU Anstead, GM Owens, AD AF Anstead, GM Owens, AD TI Recent advances in the treatment of infections due to resistant Staphylococcus aureus SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review DE dalbavancin; daptomycin; linezolid; oritavancin; tigecycline ID VENTILATOR-ASSOCIATED PNEUMONIA; SKIN-STRUCTURE INFECTIONS; IN-VITRO; GLYCOPEPTIDE ANTIBIOTICS; RETROSPECTIVE ANALYSIS; COMPLICATED SKIN; VANCOMYCIN; EXPERIENCE; SUSCEPTIBILITY; MULTICENTER AB Purpose of review This paper reviews recent data on the treatment of infections caused by drug-resistant Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This review will focus on new findings reported in the English-language medical literature from June 2003 to September 2004. Recent findings Despite the emergence of resistant and multidrug-resistant S. aureus, we have three effective drugs in clinical use for which little resistance has been observed: quinupristin-dalfopristin, linezolid, and daptomycin. Linezolid looks particularly promising in the treatment of MRSA pneumonia. Daptomycin displays rapid bactericidal activity in vitro, but, so far, clinical trials have only been conducted for the treatment of skin and soft-tissue infections. There are three drugs with broad-spectrum activity against Gram-positive organisms at an advanced stage of testing: two new glycopeptides with potent bacteriocidal activity and long half-lives (oritavancin and dalbavancin), and tigecycline, a minocycline derivative. These drugs have also shown efficacy in the treatment of skin and soft-tissue infections. Summary The promising data that have emerged in the last year indicate that we may have six available drugs to treat resistant S. aureus infections within the next few years. The next goal is to determine the appropriate indications and cost-effectiveness of each of these drugs in our treatment strategy against S. aureus and other Gram-positive pathogens. C1 Dept Vet Affairs Med Ctr, S Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. RP Anstead, GM (reprint author), Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM anstead@uthscsa.edu NR 45 TC 42 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 2004 VL 17 IS 6 BP 549 EP 555 DI 10.1097/00001432-200412000-00007 PG 7 WC Infectious Diseases SC Infectious Diseases GA 879HB UT WOS:000225705900006 PM 15640709 ER PT J AU Ray, KK Cannon, CP AF Ray, KK Cannon, CP TI Intensive statin therapy in acute coronary syndromes: clinical benefits and vascular biology SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE coagulation; endothelial function; inflammation; statins ID HMG-COA REDUCTASE; C-REACTIVE PROTEIN; ATHEROSCLEROTIC PLAQUE RUPTURE; ENDOTHELIAL PROGENITOR CELLS; RANDOMIZED CONTROLLED-TRIAL; RISK-ASSESSMENT STRATEGIES; SMOOTH-MUSCLE-CELLS; ARTERY-DISEASE; FAMILIAL HYPERCHOLESTEROLEMIA; CARDIOVASCULAR RISK AB Purpose of review The results of a landmark clinical study comparing intensive statin therapy with conventional statin therapy, in patients with acute coronary syndromes (ACS), are reviewed. The mechanisms behind these results are analysed drawing data from vascular and cell biology. Recent findings The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) study showed that intensive statin therapy with 80 mg of atorvastatin to achieve a low-density lipoprotein cholesterol of 62 mg/dl resulted in a 3.9% absolute and a 16% relative risk reduction in death or major cardiovascular events up to 2 years, compared to 40 mg of pravastatin, in patients with ACS. The results were especially significant as intensive statin therapy resulted in a very early benefit (<30 days) and occurred against a background of percutaneous coronary intervention (69%) for the index admission and high use of medications for secondary prevention. The PROVE IT and the Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) C-reactive protein sub-study also showed that atorvastatin (80 mg) resulted in a significant reduction in markers of inflammation, whilst the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study showed that intensive statin therapy was associated with reduced progression of atherosclerosis compared with conventional doses of statins. Summary Intensive statin therapy results in a significant early reduction in adverse cardiac events in ACS patients which are sustained over 2 years. The early benefits seen are likely to result from modulation of inflammation, endothelial function and coagulation, i.e. the pleiotropic effects, whereas the greater reduction in low-density lipoprotein cholesterol results in reduced long-term events. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP Ray, KK (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM kkray@partners.org NR 59 TC 36 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD DEC PY 2004 VL 15 IS 6 BP 637 EP 643 DI 10.1097/00041433-200412000-00003 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 877FI UT WOS:000225552800002 PM 15529022 ER PT J AU Drappatz, J Wen, PY AF Drappatz, J Wen, PY TI Non-cytotoxic drugs as potential treatments for gliomas SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE angiogenesis; intratumoral therapy; malignant gliomas; targeted molecular therapy ID HIGH-GRADE GLIOMAS; PHASE-II TRIAL; RECURRENT MALIGNANT GLIOMA; CONVECTION-ENHANCED DELIVERY; TYROSINE KINASE INHIBITOR; HIGH-DOSE TAMOXIFEN; GLIOBLASTOMA-MULTIFORME; BRAIN-TUMORS; ANTIANGIOGENIC ACTIVITY; CHIMERIC PROTEIN AB Purpose of review Despite advances in surgery, radiation therapy, and chemotherapy, malignant gliomas continue to be associated with a poor prognosis. Even the most intensive combinations of radiotherapy and chemotherapy are not curative. In recent years our understanding of how tumor cells overcome cell cycle control, evade programmed cell death, induce blood vessel formation, and escape immune regulation has increased substantially. Significant efforts are directed towards the development of novel experimental therapies to target these molecular and biological mechanisms that lead to the development and growth of brain tumors. This review summarizes the most recent developments in non-cytotoxic therapy for malignant gliomas, such as targeted molecular drugs, inhibitors of angiogenesis and intratumoral therapy. Recent findings The first generation of studies using these novel therapies is nearing completion. In general, most of these treatments are well tolerated, but single-agent activity is modest. There is significant interest in combining these therapies with each other and with conventional cytotoxic therapies such as radiation therapy and chemotherapy. Summary These new therapeutic approaches for malignant gliomas are showing modest activity. As we learn to use these agents more effectively, and as an increasing number of new and potentially promising agents are developed, it is likely that therapies for malignant gliomas will improve over the next few years. C1 Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brain Tumor Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org NR 98 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD DEC PY 2004 VL 17 IS 6 BP 663 EP 673 DI 10.1097/00019052-200412000-00005 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 878XY UT WOS:000225682000004 PM 15542974 ER PT J AU Torres, A Niemeyer, A Berkes, B Marra, D Schanbacher, C Gonzalez, S Owens, M Morgan, B AF Torres, A Niemeyer, A Berkes, B Marra, D Schanbacher, C Gonzalez, S Owens, M Morgan, B TI 5% imiquimod cream and reflectance-mode confocal microscopy as adjunct modalities to mohs micrographic surgery for treatment of basal cell carcinoma SO DERMATOLOGIC SURGERY LA English DT Article ID IMMUNE-RESPONSE; REAL-TIME AB BACKGROUND. Imiquimod is an immune response modifier that up-regulates cytokines and has been shown in clinical studies to reduce or clear basal cell carcinoma tumors when applied topically. OBJECTIVE. The objectives were to evaluate the efficacy of 5% imiquimod cream in treating basal cell carcinoma preceding excision by Mohs micrographic surgery and to determine if reflectance-mode confocal microscopy is useful to establish the need for surgical intervention after imiquimod treatment. METHODS. Subjects applied study cream to one biopsy-confirmed basal cell carcinoma tumor 5 x/week for 2, 4, or 6 weeks in this vehicle-controlled, double-blind study. Confocal microscopy was used for the 6-week treatment group to examine the target tumor area at each interval visit and immediately before Mohs micrographic surgery. After the Mohs micrographic surgery excision, the tissue was evaluated histologically, and the excision area was measured. Confocal microscopy readings were correlated to the histologic diagnosis. RESULTS. Tumors cleared or the target tumor area was reduced in subjects in the 4- and 6-week dosing regimens. Confocal microscopy assessments correlated well with the histologic diagnosis. CONCLUSION. Imiquimod improved excision results relative to vehicle when used for treating basal cell carcinoma before Mohs micrographic surgery. Confocal microscopy assessments correlated well with tumor response to therapy, suggesting that confocal microscopy may help determine the need for surgery. C1 Loma Linda Univ, Med Ctr, Dermatol Off, Fac Med Off, Loma Linda, CA 92354 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02115 USA. 3M Pharmaceut, St Paul, MN USA. RP Torres, A (reprint author), Loma Linda Univ, Med Ctr, Dermatol Off, Fac Med Off, 11370 Anderson St,Suite 2600, Loma Linda, CA 92354 USA. EM ABELT@aol.com NR 14 TC 45 Z9 48 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD DEC PY 2004 VL 30 IS 12 BP 1462 EP 1469 DI 10.1111/j.1524-4725.2004.30504.x PN 1 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 877NF UT WOS:000225576600006 PM 15606733 ER PT J AU Joseph, EM AF Joseph, EM TI Zebrafish IRX1b in the embryonic cardiac ventricle SO DEVELOPMENTAL DYNAMICS LA English DT Article DE iroquois; heart; cardiac; development; conduction system; Danio rerio; zebrafish ID CONDUCTING PURKINJE-FIBERS; IROQUOIS HOMEOBOX GENE; EPIGENETIC FACTOR; HEART; SYSTEM; IDENTIFICATION; EXPRESSION; DIFFERENTIATION; REVEALS; GENOME AB The synchronous contraction of the vertebrate heart requires a conduction system. While coordinated contraction of the cardiac chambers is observed in zebrafish larvae, no histological evidence yet has been found for the existence of a cardiac conduction system in this tractable teleost. The homeodomain transcription factor gene IRX1 has been shown in the mouse embryo to be a marker of cells that give rise to the distinctive cardiac ventricular conduction system. Here, I demonstrate that zebrafish IRX1b is expressed in a restricted subset of ventricular myocytes within the embryonic zebrafish heart. IRX1b expression occurs as the electrical maturation of the heart is taking place, in a location analogous to the initial expression domain of mouse IRX1. The gene expression pattern of IRX1b is altered in silent heart genetic mutant embryos and in embryos treated with the endothelin receptor antagonist bosentan. Furthermore, injection of a morpholino oligonucleotide targeted to block IRX1b translation slows the heart rate. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Joseph, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM elaine@post.harvard.edu NR 30 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2004 VL 231 IS 4 BP 720 EP 726 DI 10.1002/dvdy.20172 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 874DM UT WOS:000225331100007 PM 15497138 ER PT J AU Bei, M Stowell, S Maas, R AF Bei, M Stowell, S Maas, R TI Msx2 controls ameloblast terminal differentiation SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Msx2; Bmp4; laminins; tooth development; amelogenesis ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; ALPHA-3 CHAIN GENE; HOMOZYGOUS NONSENSE MUTATION; TOOTH DEVELOPMENT; HOMEOBOX GENE; ENAMEL KNOT; MOUSE TOOTH; EXPRESSION PATTERNS; LAMININ-5 SUBUNITS; HOX-7 EXPRESSION AB Late tooth morphogenesis is characterized by a series of events that determine cusp morphogenesis and the histodifferentiation of epithelial cells into enamel-secreting ameloblasts. Mice lacking the homeobox gene Msx2 exhibit defects in cusp morphogenesis and in the process of amelogenesis. To better understand the basis of the Msx2 mutant tooth defects, we have investigated the function of Msx2 during late stages of tooth morphogenesis. Cusp formation is thought to be under the control of the enamel knot, which has been proposed to act as an organizing center during this process (Vaahtokari et al. [1996] Mech. Dev. 54:39-43). Bone morphogenetic protein-4 (BMP4) has been suggested to mediate termination of enamel knot signaling by means of regulation of programmed cell death (Jernvall et al. [1998] Development 125-161-169). Here, we show that Bmp4 expression in the enamel knot is Msx2-dependent. We further show that during amelogenesis Msx2 is required for the expression of the extracellular matrix gene Laminin 5 alpha 3, which is known to play an essential role during ameloblast differentiation. This result thus provides a paradigm for understanding how transcription factors and extracellular matrix can be integrated into a developmental pathway controlling cell differentiation. (C) 2004 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med & Dent, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. RP Bei, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM marianna.bei@cbrc2.mgh.harvard.edu FU NIDCR NIH HHS [K22 DE 14230, R01DE11987] NR 52 TC 38 Z9 40 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2004 VL 231 IS 4 BP 758 EP 765 DI 10.1002/dvdy.20182 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 874DM UT WOS:000225331100011 PM 15499554 ER PT J AU Bates, SH Dundon, TA Seifert, M Carlson, M Maratos-Filer, E Myers, MG AF Bates, SH Dundon, TA Seifert, M Carlson, M Maratos-Filer, E Myers, MG TI LRb-STAT3 signaling is required for the neuroendocrine regulation of energy expenditure by leptin SO DIABETES LA English DT Article ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MELANOCYTE-STIMULATING HORMONE; BROWN ADIPOSE-TISSUE; GENE-EXPRESSION; SYNTHESIZING NEURONS; NEUROPEPTIDE-Y; RECEPTOR GENE; BODY-WEIGHT; OBESE GENE; ACTIVATION AB Secretion of leptin from adipose tissue communicates body energy status to the neuroendocrine system by activating the long form of the leptin receptor (LRb). Lack of leptin or LRb (as in db/db mice) results in obesity that stems from the combined effects of hyperphagia and decreased energy expenditure. We have previously generated mice in which LRb is replaced with a mutant LRb (LRbS1138) that specifically disrupts LRb-->STAT3 (signal transducer and activator of transcription-3) signaling; mice homozygous for this mutant (s/s) display increased feeding and are obese. We have now examined energy expenditure in s/s and db/db mice. Consistent with the increased lean body mass of s/s animals, locomotor activity and acute cold tolerance (partly a measure of shivering thermogenesis) in s/s mice were modestly but significantly improved compared with db/db mice, although they were decreased compared with wild-type mice. Total and resting metabolic rates were similarly depressed in s/s and db/db mice, however. Indeed, s/s and db/db mice display similar reductions in thyroid function and brown adipose tissue expression of uncoupling protein-1, which is regulated by sympathetic nervous system (SNS) tone. Thus, the LRb-->STAT3 signal is central to both the control of energy expenditure by leptin and the neuroendocrine regulation of the SNS and the thyroid axis. C1 Univ Michigan, Sch Med, Dept Internal Med Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Myers, MG (reprint author), Univ Michigan, Sch Med, Dept Internal Med, Div Endocrinol Diabet & Metab, 1150 W Med Ctr Dr,4301 MSRB 3,Box 0638, Ann Arbor, MI 48109 USA. EM mgmyers@umich.edu FU NIDDK NIH HHS [DK57768, DK56731, DK53978] NR 42 TC 88 Z9 93 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 IS 12 BP 3067 EP 3073 DI 10.2337/diabetes.53.12.3067 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100005 PM 15561935 ER PT J AU Zinman, B Kahn, SE Haffner, SM O'Neill, MC Heise, MA Freed, MI AF Zinman, B Kahn, SE Haffner, SM O'Neill, MC Heise, MA Freed, MI CA ADOPT Study Grp TI Phenotypic characteristics of GAD antibody-positive recently diagnosed patients with type 2 diabetes in North America and Europe SO DIABETES LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; MELLITUS; PREDICTION; ADULTS; SENSITIVITY; SECRETION; PROGRAM; DISEASE AB A number of patients with type 2 diabetes are GAD antibody positive. A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind clinical trial in recently diagnosed drug-naive patients with type 2 diabetes that allows for the evaluation of GAD positivity in the context of anthropometric and biochemical characteristics. Of the 4,134 subjects enrolled in ADOPT for whom GAD status was obtained, 174 (4.2%) were GAD positive, with the prevalence of GAD antibodies being similar in North America (4.7%) and Europe (3.7%). Although BMI and age were similar, GAD-positive patients had a lower fasting insulin level, compatible with them being more insulin sensitive. The lower fasting insulin concentration was accompanied by a decreased early insulin response to oral glucose. However, when this insulin response was corrected for the degree of insulin sensitivity, GAD-positive and -negative patients had similar beta-cell function. Consistent with the difference in insulin sensitivity, GAD-positive patients had higher HDL cholesterol and lower triglyceride levels. In the GAD-positive individuals, the prevalence of the metabolic syndrome as defined by NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) was also lower (74.1 vs. 83.7%, P = 0.0009). These phenotypic differences may underlie a potential difference in the natural history of hyperglycemia and its clinical outcomes. C1 Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. GlaxoSmithKline, King Of Prussia, PA USA. RP Kahn, SE (reprint author), VA Med Ctr 151, 1660 S Columbia Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu RI Zinman, Bernard/E-7266-2013; Hegele, Robert/G-3301-2011; OI Kahn, Steven/0000-0001-7307-9002 NR 22 TC 65 Z9 68 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 DEC PY 2004 VL 53 IS 12 BP 3193 EP 3200 DI 10.2337/diabetes.53.12.3193 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100020 PM 15561950 ER PT J AU Almind, K Kahn, CR AF Almind, K Kahn, CR TI Genetic determinants of energy expenditure and insulin resistance in diet-induced obesity in mice SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; SKELETAL-MUSCLE; MOUSE STRAINS; BODY-WEIGHT; LOCI; METABOLISM; ACTIVATION; EXPRESSION; ADIPOSITY; TRAITS AB Diet-induced obesity is the primary determinant of the current, epidemic of diabetes. We have explored the role of genetics in this phenomenon, using C57B1/6 (B6), 129S6/SvEvTac (129), and intercross (B6 x 129)F2 mice on a low- or high-fat diet. Over an 18-week period, B6 and F2 mice gained more weight, had higher levels of insulin and leptin, and showed greater glucose intolerance than 129 mice, despite lower food intake. By contrast, metabolic rate and diet-induced thermogenesis were significantly higher in the 129 mice. Genome-wide scans identified several quantitative trait loci, including a quantitative trait locus that was linked with hyperinsulinemia/insulin resistance on chromosome 14 in a region similar to that seen in mice with genetically induced insulin resistance. Microarray analysis indicated significant changes in expression levels between B6 and 129 mice in the identified chromosomal area of Wnt5a and protein kinase Cdelta (PKCdelta). Thus, caloric efficiency, i.e., the "thrifty gene," is a dominant-acting genetic determinant of diet-induced obesity in mice and can be linked to a locus on chromosome 14, including genes linked to adipose development and insulin sensitivity. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu FU NIDDK NIH HHS [DK31036, DK45935, DK60837-02] NR 48 TC 133 Z9 136 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 IS 12 BP 3274 EP 3285 DI 10.2337/diabetes.53.12.3274 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100030 PM 15561960 ER PT J AU Florez, JC Sjogren, M Burtt, N Orho-Melander, M Schayer, S Sun, M Almgren, P Lindblad, U Tuomi, T Gaudet, D Hudson, TJ Daly, MJ Ardlie, KG Hirschhorn, JN Altshuler, D Groop, L AF Florez, JC Sjogren, M Burtt, N Orho-Melander, M Schayer, S Sun, M Almgren, P Lindblad, U Tuomi, T Gaudet, D Hudson, TJ Daly, MJ Ardlie, KG Hirschhorn, JN Altshuler, D Groop, L TI Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes SO DIABETES LA English DT Article ID AMINO-ACID POLYMORPHISM; BETA-CELL FUNCTION; GENETIC ASSOCIATION; PPAR-GAMMA; GLUCOSE-TOLERANCE; COMPLEX TRAITS; E23K VARIANT; RESISTANCE; SECRETION; METAANALYSIS AB The insulin receptor substrate (IRS)-1 is an important component of the insulin signal transduction cascade. Several reports suggest that a Gly-->Arg change in codon 972 is associated with type 2 diabetes and related traits, and a recent meta-analysis reported a modest but nominally significant association with type 2 diabetes (odds ratio [OR] 1.25 in favor of carriers of the Arg allele [95% CI 1.05-1.48). To test the reproducibility of the model in a recent meta-analysis, we examined genotype-phenotype correlation in three large Caucasian samples (not previously reported for this variant) totaling 9,000 individuals (estimated to have >95% power to obtain a P<0.05 for the OR of 1.25 estimated in the meta-analysis). In our combined sample, comprising 4,279 case and 3,532 control subjects, as well as 1,189 siblings discordant for type 2 diabetes, G972R was not associated with type 2 diabetes (OR 0.96 [0.84-1.10], P = 0.60). Genotype at G972R had no significant effect on various measures of insulin secretion or insulin resistance in a set of Scandinavian samples in whom we had detailed phenotypic data. In contrast, the well-documented associations of peroxisome proliferator-activated receptor gamma P12A and Kir6.2 E23K with type 2 diabetes are both robustly observed in these 9,000 subjects, including an additional (previously unpublished) confirmation of Kir6.2 E23K and type 2 diabetes in the Polish and North American samples (combined OR 1.15 [1.05-1.261, P = 0.001). Despite genotyping 9,000 people and >95% power to reproduce the estimated OR from the recent meta-analysis, we were unable to replicate the association of the IRS-1 G972R polymorphism with type 2 diabetes. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Lund Univ, Univ Hosp MAS, Dept Community Med, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Folkhalsan Genet Inst, Folkhalsan Res Ctr, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Univ Montreal, Chicoutimi Hosp, Community Genom Ctr, Quebec City, PQ, Canada. McGill Univ, Montreal, PQ, Canada. Genome Quebec Innovat Ctr, Montreal, PQ, Canada. Genome Collaborat, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Groop, L (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM leif.groop@endo.mas.lu.se RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NIDDK NIH HHS [1 K23 DK65978-01] NR 32 TC 53 Z9 56 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 IS 12 BP 3313 EP 3318 DI 10.2337/diabetes.53.12.3313 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874CI UT WOS:000225328100035 PM 15561965 ER PT J AU Roder, ME Kahn, SE AF Roder, ME Kahn, SE TI Suppression of beta-cell secretion by sontatostatin does not fully reverse the disproportionate proinsulinemia of type 2 diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 5th Servier-IGIS Symposium CY MAR 18-20, 2004 CL St Jean Cap Ferrat, FRANCE ID C-PEPTIDE; INSULIN-RESISTANCE; ELEVATED PROINSULIN; NIDDM; HYPERPROINSULINEMIA; MECHANISM; ANTISERA; CAPACITY; MELLITUS; RELEASE AB Disproportionate hyperproinsulinemia is a feature of beta-cell dysfunction in type 2 diabetes. It has been hypothesized that this abnormality represents an intrinsic abnormality of the beta-cell and/or may result from an increase in beta-cell secretory demand. To address this, six patients with type 2 diabetes and six age- and BMI-matched normal subjects received a combined 3-h insulin and somatostatin clamp to decrease beta-cell secretory demand. An arginine stimulation test was performed before and at the end of the clamp to measure beta-cell peptide release. In keeping with the reduction in secretory demand, C-peptide levels were suppressed by 60-80% during the clamp, as were proinsulin (PI) levels. The arginine-stimulated PI/C-peptide ratio decreased in the diabetic subjects from 4.4 +/- 1.5% before to 1.8 +/- 0.5% after the clamp (P < 0.01). This latter ratio was similar to that observed in the normal subjects before the somatostatin infusion (1.5 +/- 0.3%). In the normal subjects, after the clamp the PI/C-peptide ratio had decreased to 0.8 +/- 0.3% (P < 0.01). Thus, the postclamp PI/C-peptide ratio in the subjects with type 2 diabetes was elevated compared with that in the normal subjects (P < 0.05). Based on these observations, while relief of secretory demand on beta-cells by somatostatin decreases the disproportionate elevation in PI levels in patients with type 2 diabetes, the failure to normalize this measure suggests that an intrinsic abnormality of beta-cell function exists in subjects with type 2 diabetes that may be aggravated by increased secretory demand. C1 Univ Copenhagen, Bispebjerg Hosp, Clin Internal Med 1, Endocrine Sect, DK-2400 Copenhagen NV, Denmark. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Roder, ME (reprint author), Univ Copenhagen, Bispebjerg Hosp, Clin Internal Med 1, Endocrine Sect, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM mir@dadlnet.dk FU NCRR NIH HHS [RR-37] NR 22 TC 4 Z9 4 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 SU 3 BP S22 EP S25 DI 10.2337/diabetes.53.suppl_3.S22 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 875YU UT WOS:000225460000004 PM 15561914 ER PT J AU Weir, GC Bonner-Weir, S AF Weir, GC Bonner-Weir, S TI Five stages of evolving beta-cell dysfunction during progression to diabetes SO DIABETES LA English DT Article; Proceedings Paper CT 5th Servier-IGIS Symposium CY MAR 18-20, 2004 CL St Jean Cap Ferrat, FRANCE ID IMPAIRED GLUCOSE-TOLERANCE; HUMAN PANCREATIC-ISLETS; INSULIN-SECRETION; CHRONIC HYPERGLYCEMIA; GENE-EXPRESSION; FATTY RAT; MELLITUS; MASS; APOPTOSIS; DIFFERENTIATION AB This article proposes five stages in the progression of diabetes, each of which is characterized by different changes in beta-cell mass, phenotype, and function. Stage I is compensation: insulin secretion increases to maintain normoglycemia in the face of insulin resistance and/or decreasing -cell mass. This stage is characterized by maintenance of differentiated function with intact acute glucose-stimulated insulin secretion (GSIS). Stage 2 occurs when glucose levels start to rise, reaching similar to5.0-6.5 mmol/l; this is a stable state of beta-cell adaptation with loss of beta-cell mass and disruption of function as evidenced by diminished GSIS and beta-cell dedifferentiation. Stage 3 is a transient unstable period of early decompensation in which glucose levels rise relatively rapidly to the frank diabetes of stage 4, which is characterized as stable decompensation with more severe beta-cell dedifferentiation. Finally, stage 5 is characterized by severe decompensation representing a profound reduction in beta-cell mass with progression to ketosis. Movement across stages 1-4 can be in either direction. For example, individuals with treated type 2 diabetes can move from stage 4 to stage 1 or stage 2. For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU NIDDK NIH HHS [DK-36836, DK-35449] NR 46 TC 363 Z9 389 U1 4 U2 50 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 2004 VL 53 SU 3 BP S16 EP S21 DI 10.2337/diabetes.53.suppl_3.S16 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 875YU UT WOS:000225460000003 PM 15561905 ER PT J AU Pitman, MB Faquin, WC AF Pitman, MB Faquin, WC TI The fine-needle aspiration biopsy cytology of pancreatoblastoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE pancreas; pediatric neoplasm; pancreatoblastoma; fine-needle aspiration biopsy; cytology ID ACINAR CELL-CARCINOMA; PANCREATIC TUMORS; CHILDHOOD AB We describe the clinical, cytological, histological, and immunohistochemical features of primary and metastatic pancreatoblastoma (PBL), a rare primary pancreatic malignancy of both adults and children. An 18-yr-old male patient presented with abdominal pain, weight loss, and diarrhea and had a 9-cm pancreatic mass that was revealed by CT scan. The fine-needle aspiration biopsy (FNAB) smears from the pancreas specimen and the lung metastasis were cellular and were composed of a combination of solid sheets; three-dimensional, loosely cohesive epithelial groups, and primitive spindled mesenchymal tissue with focal cartilage,formation. Acinar formations were best appreciated on cell block preparations, and squamoid corpuscles were seen only on cell block. Zymogen granules were demonstrated in a subset of the epithelial cells using periodic-acid Schiff stains with and without diastase and dual acinar-endocrine differentiation was evident using a focused panel of immunohistochemical stains. Acinar-cell carcinoma (ACC) is the most difficult neoplasm to distinguish from PBL, both clinically and cytologically, especially in young children. The key to distinguishing them is to note the presence of squamous corpuscles and/or heterologous elements such as cartilage. Given the increasing utility of FNAB in the investigation of pancreatic masses, it is important for the pathologist to be familiar with the morphological,features of this tumor, especially because preoperative diagnosis provides an opportunity for preoperative therapy before resection. (C) 2004 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, James Homer Wright Dept Pathol, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mpitman@partners.org NR 18 TC 17 Z9 18 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD DEC PY 2004 VL 31 IS 6 BP 402 EP 406 DI 10.1002/dc.20128 PG 5 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 876LB UT WOS:000225497200009 PM 15540188 ER PT J AU Craig, WA Bhavnani, SM Ambrose, PG AF Craig, WA Bhavnani, SM Ambrose, PG TI The inoculum effect: Fact or artifact? SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Editorial Material ID ESCHERICHIA-COLI; PNEUMONIAE; CEFEPIME C1 William S Middleton Mem Vet Adm Med Ctr, Clin Pharmacol Sect, Dept Med, Madison, WI USA. Ordway Res Inst Inc, Inst Clin Pharmacodynam, Albany, NY USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY 14260 USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, Clin Pharmacol Sect, Dept Med, Madison, WI USA. EM pgambrose@aol.com NR 12 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD DEC PY 2004 VL 50 IS 4 BP 229 EP 230 DI 10.1016/j.diagmicrobio.2004.07.006 PG 2 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 880WQ UT WOS:000225821100001 PM 15582294 ER PT J AU O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Ko, CY AF O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Ko, CY TI Are survival rates different for young and older patients with rectal cancer? SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Association-for-Academic-Surgery CY NOV 13-15, 2003 CL Sacramento, CA SP Assoc Acad Surg DE rectal; cancer; young; survival; population-based; SEER ID COLORECTAL-CANCER; PATIENTS LESS; COLON; AGE; CARCINOMA; ADENOCARCINOMA; PROGNOSIS; DECADES; ADULTS AB PURPOSE: Although it is generally believed that young patients with rectal cancer have worse survival rates, no comprehensive analysis has been reported. This study uses a national-level, population-based cancer registry to compare rectal cancer outcomes between young vs. older populations. METHODS: All patients with rectal carcinoma in the Surveillance, Epidemiology, and End Results cancer database from 1991 to 1999 were evaluated. Young (range, 2040 years; n = 466) and older groups (range, 60-80 years; n = 11,312) were compared for patient and tumor characteristics, treatment patterns, and five-year overall and stage-specific survival. Cox multivariate regression analysis was performed to identify predictors of survival. RESULTS: Mean ages for the groups were 34.1 and 70 years. The young group was comprised of more black and Hispanic patients compared with the older group (P < 0.001). Young patients were more likely to present with late-stage disease (young vs. older: Stage 111, 27 vs. 20 percent respectively, P < 0.001; Stage IV, 17.4 vs. 13.6 percent respectively, P < 0.02). The younger group also had worse grade tumors (poorly differentiated 24.3 vs. 14 percent respectively, P < 0.001). Although the majority of both groups received surgery (85 percent for each), significantly more young patients received radiation (P < 0.001). Importantly, overall and stage-specific, five-year survival rates were similar for both groups (P = not significant). CONCLUSIONS: Although previous studies have found young rectal cancer patients to have poorer survival compared with older patients, this population-based study shows that young rectal cancer patients seem to have equivalent overall and stage-specific survival. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 Le Conte Ave,Room 73-215, Los Angeles, CA 90095 USA. EM jbocjboc@hotmail.com NR 29 TC 71 Z9 78 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD DEC PY 2004 VL 47 IS 12 BP 2064 EP 2069 DI 10.1007/s10350-004-0738-1 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 878MD UT WOS:000225650000011 PM 15657655 ER PT J AU Beisswenger, P Heine, RJ Leiter, LA Moses, A Tuomilehto, J AF Beisswenger, P Heine, RJ Leiter, LA Moses, A Tuomilehto, J TI Prandial glucose regulation in the glucose triad - Emerging evidence and insights SO ENDOCRINE LA English DT Article DE diabetes; type 2 diabetes; postprandial glucose; postprandial hyperglycemia; hyperlipidemia; hyper-triglyceridemia; cardiovascular risk ID TYPE-2 DIABETES-MELLITUS; IMPAIRED FASTING GLUCOSE; CORONARY-HEART-DISEASE; RISK-FACTOR; CARDIOVASCULAR-DISEASE; PLASMA-GLUCOSE; POSTPRANDIAL HYPERGLYCEMIA; MYOCARDIAL-INFARCTION; DIAGNOSTIC-CRITERIA; OXIDATIVE STRESS AB While it is well established that overall glycemic control reduces the complications of diabetes, the role of fasting glycemia versus postprandial glycemia in the pathophysiology of diabetes and its complications, and the relative importance of these parameters as specific targets of therapy, remain controversial. Evidence that postprandial glucose (PPG) plays an independent, modifiable role in cardiovascular disease is accumulating, largely from epidemiological studies. A large number of epidemiological studies show that high postprandial glucose is an independent risk factor for cardiovascular disease: indeed, a more powerful risk factor than fasting glucose or HbA(1c). Pathophysiological hypotheses that support these observations include the contribution of postprandial glucose to HbA(1c); postprandial glucose as a surrogate marker for other cardiovascular risk factors, serum lipids and triglycerides in particular; and direct toxicity of elevated glucose levels attributed to "spikes" in glucose concentration following caloric ingestion. Early interventional data suggest that therapy targeted at postprandial glucose can have a favorable impact on cardiovascular events. While more interventional studies clearly are needed, the growing weight of evidence supports a therapeutic approach more directed at excessive prandial glycemic excursions that are characteristic of both type 1 and type 2 diabetes. C1 Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Lebanon, NH 03766 USA. Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. Univ Toronto, St Michaels Hosp, Toronto, ON, Canada. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. Univ Helsinki, Acad Finland, Natl Publ Hlth Inst, Helsinki, Finland. RP Moses, A (reprint author), 100 Coll Rd, Princeton, NJ USA. NR 48 TC 15 Z9 16 U1 1 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1355-008X J9 ENDOCRINE JI Endocrine PD DEC PY 2004 VL 25 IS 3 BP 195 EP 202 DI 10.1385/ENDO:25:3:195 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 905DU UT WOS:000227548700001 PM 15758245 ER PT J AU Hall, JE AF Hall, JE TI Neuroendocrine physiology of the early and late menopause SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; REPRODUCTIVE-AGED WOMEN; LUTEINIZING-HORMONE; POSTMENOPAUSAL WOMEN; MENSTRUAL-CYCLE; ACTIVIN-A; INHIBIN-B; OLDER WOMEN; HYPOTHALAMIC FUNCTION AB The average age at menopause is approximately 51 years, but there is now evidence that reproductive aging begins far earlier and is a much more gradual process than the events marked clinically by irregular cycles and the subsequent final menstrual period (FMP). Recent studies of reproductive aging have provided important insights into the control of reproduction in women; in addition they have defined the changes in neuroendocrine and ovarian hormones that accompany this dynamic period and have provided information that is critical to management of infertility in older reproductive-aged women and to understanding the symptomatology of the transition to menopause. This article reviews the neuroendocrine control of reproduction in women and describes the current understanding of the hormonal changes of the early and late menopause that derive from studies in older reproductive-aged women and postmenopausal women. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St,BHX-5, Boston, MA 02114 USA. EM jehall@partners.org FU NCRR NIH HHS [M01 RR01066]; NIA NIH HHS [R01 AG13241, R01 AG013241]; NICHD NIH HHS [R01 HD42708, K24 HD01290] NR 73 TC 43 Z9 45 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 2004 VL 33 IS 4 BP 637 EP + DI 10.1016/j.ecl.2004.08.002 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 871TI UT WOS:000225156100003 PM 15501638 ER PT J AU Hauser, R Meeker, JD Park, S Silva, MJ Calafat, AM AF Hauser, R Meeker, JD Park, S Silva, MJ Calafat, AM TI Temporal variability of urinary phthalate metabolite levels in men of reproductive age SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; human; phthalates; reliability; urine ID HUMAN SEMEN PARAMETERS; DI(2-ETHYLHEXYL) PHTHALATE; QUANTITATIVE DETECTION; EXPOSURE; POPULATION; RATS AB Phthalates are a family of multifunctional chemicals widely used in personal care and other consumer products. The ubiquitous use of phthalates results in human exposure through multiple sources and routes, including dietary ingestion, dermal absorption, inhalation, and parenteral exposure from medical devices containing phthalates. We explored the temporal variability over 3 months in urinary phthalate metabolite levels among 11 men who collected up to nine urine samples each during this time period. Eight phthalate metabolites were measured by solid-phase extraction-high-performance liquid chromatography-tandem mass spectrometry. Statistical analyses were performed to determine the between- and within-subject variance apportionment, and the sensitivity and specificity of a single urine sample to classify a subject's 3-month average exposure. Five of the eight phthalates were frequently detected. Monoethyl phthalate (MEP) was detected in 100% of samples; monobutyl phthalate, monobenzyl phthalate, mono-2-ethylhexyl phthalate (MEHP), and monomethyl phthalate were detected in > 90% of samples. Although we found both substantial day-to-day and month-to-month variability in each individual's urinary phthalate metabolite levels, a single urine sample was moderately predictive of each subject's exposure over 3 months. The sensitivities ranged from 0.56 to 0.74. Both the degree of between- and within-subject variance and the predictive ability of a single urine sample differed among phthalate metabolites. In particular, a single urine sample was most predictive for MEP and least predictive for MEHP. These results suggest that the most efficient exposure assessment strategy for a particular study may depend on the phthalates of interest. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES00002, ES09718] NR 31 TC 198 Z9 200 U1 4 U2 23 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 2004 VL 112 IS 17 BP 1734 EP 1740 DI 10.1289/ehp.7212 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 880ID UT WOS:000225781300052 PM 15579421 ER PT J AU Gerson, LW Emond, JA Camargo, CA AF Gerson, Lowell W. Emond, Jennifer A. Camargo, Carlos A., Jr. TI US emergency department visits for hip fracture, 1992-2000 SO EUROPEAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE Aged; analgesia; emergency department; hip fracture AB Background: Hip fracture is a significant injury for older persons. Little has been reported about emergency department (ED) care of these patients. Objective: To characterize the management of older patients treated in the ED for hip fracture with specific attention to the use of analgesia. Methods: This study analysed data from the National Hospital Ambulatory Medical Care Survey (similar to 400 hospitals report each year) for the years 1992-2000. We included records of patients who were at least 50 years old and had a diagnosis of hip fracture (International Classification of Disease, 9th revision, clinical modification 820-820.9) in any of the three fields allowed for recording diagnosis. Results: There were 1 935 000 ED visits (approximate to 215 000 a year), predominately among older white women. The rate in those over 80 years old was 25 times that of the youngest group. Fifty-six per cent of patients received analgesia (44% narcotics). There were no ethnic or racial distinctions in the use of analgesia. Conclusions: The ED visit presents a largely untapped opportunity for focused efforts in fall and hip fracture prevention, especially in countries with comprehensive geriatric services and well integrated healthcare delivery systems. Despite the high likelihood of pain, the administration of analgesics appears to be low and may be a worthy focus for practice improvement. (C) 2004 Lippincott Williams & Wilkins. C1 [Gerson, Lowell W.] Northeastern Ohio Univ Coll Med, Dept Community Hlth Sci, Rootstown, OH 44272 USA. [Emond, Jennifer A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Gerson, LW (reprint author), Northeastern Ohio Univ Coll Med, Dept Community Hlth Sci, 4209 State Route 44,POB 95, Rootstown, OH 44272 USA. EM lgerson@neoucom.edu FU Emergency Medicine Foundation Center of Excellence Award, Dallas, TX, USA FX Sponsorship: Ms Emond and Dr Camargo are supported, in part, by the Emergency Medicine Foundation Center of Excellence Award, Dallas, TX, USA. NR 21 TC 7 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0969-9546 EI 1473-5695 J9 EUR J EMERG MED JI Eur. J. Emerg. Med. PD DEC PY 2004 VL 11 IS 6 BP 323 EP 328 DI 10.1097/00063110-200412000-00005 PG 6 WC Emergency Medicine SC Emergency Medicine GA V41AD UT WOS:000209518200005 PM 15542989 ER PT J AU Hao, K Li, C Rosenow, C Wong, WH AF Hao, K Li, C Rosenow, C Wong, WH TI Detect and adjust for population stratification in population-based association study using genomic control markers: an application of Affymetrix Genechip (R) Human Mapping 10K array SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE population stratification; population-based study; association test; genomic control ID GENETIC ASSOCIATION; DIABETES-MELLITUS; DISEQUILIBRIUM; ADMIXTURE AB Population-based association design is often compromised by false or nonreplicable findings, partially due to population stratification. Genomic control (GC) approaches were proposed to detect and adjust for this confounder. To date, the performance of this strategy has not been extensively evaluated on real data. More than 10000 single-nucleotide polymorphisms (SNPs) were genotyped on subjects from four populations ( including an Asian, an African-American and two Caucasian populations) using GeneChip(R) Mapping 10 K array. On these data, we tested the performance of two GC approaches in different scenarios including various numbers of GC markers and different degrees of population stratification. In the scenario of substantial population stratification, both GC approaches are sensitive using only 20-50 random SNPs, and the mixed subjects can be separated into homogeneous subgroups. In the scenario of moderate stratification, both GC approaches have poor sensitivities. However, the bias in association test can still be corrected even when no statistical significant population stratification is detected. We conducted extensive benchmark analyses on GC approaches using SNPs over the whole human genome. We found GC method can cluster subjects to homogeneous subgroups if there is a substantial difference in genetic background. The inflation factor, estimated by GC markers, can effectively adjust for the confounding effect of population stratification regardless of its extent. We also suggest that as low as 50 random SNPs with heterozygosity >40% should be sufficient as genomic controls. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Affymetrix, Gen Collaborat, Santa Clara, CA USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Wong, WH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave,Bldg 2,Room 441, Boston, MA 02115 USA. EM wwong@hsph.harvard.edu FU NHGRI NIH HHS [1R01HG02341] NR 15 TC 32 Z9 35 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD DEC PY 2004 VL 12 IS 12 BP 1001 EP 1006 DI 10.1038/sj.ejhg.5201273 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 871VR UT WOS:000225165200004 PM 15367915 ER PT J AU Ogino, S Wilson, RB Gold, B AF Ogino, S Wilson, RB Gold, B TI New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE SMN1; SMN; spinal muscular atrophy; copy number; genetic counseling; risk assessment ID SPINAL MUSCULAR-ATROPHY; GENE DOSAGE ANALYSIS; MOTOR-NEURON GENE; SINGLE NUCLEOTIDE; COPY NUMBER; MOLECULAR ANALYSIS; RISK ASSESSMENT; MUTATION-RATE; HUMAN GENOME; SMA CARRIER AB Most spinal muscular atrophy patients lack both copies of SMN1. Loss of SMN1 ('0-copy alleles') can occur by gene deletion or SMN1-to-SMN2 gene conversion. Despite worldwide efforts to map the segmental duplications within the SMN region, most assemblies do not correctly delineate these genes. A near pericentromeric location provides impetus for the strong evidence that SMN1 and SMN2 arose from a primate-specific paralogous gene duplication. Here we meta-analyzed our recent laboratory results together with available published data, in order to calculate new mutation rates and allele/haplotype frequencies in this recalcitrant and highly unstable region of the human genome. Based on our tested assumption of compliance with Hardy-Weinberg equilibrium, we conclude that the SMN1 allele frequencies are: '0-copy disease alleles,' 0.013; '1-copy normal alleles,' 0.95; '2-copy normal alleles (ie, two copies of SMN1 on one chromosome),' 0.038; and '1 D disease alleles (SMN1 with a small intragenic mutation),' 0.00024. The SMN1 haplotype ['(SMN1 copy number)-(SMN2 copy number)'] frequencies are: '0-0,' 0.00048; '0-1,' 0.0086; '0-2,' 0.0042; '1-0,' 0.27; '1-1,' 0.66; '1-2,' 0.015; '2-0,' 0.027; and '2-1,' 0.012. Paternal and maternal de novo mutation rates are 2.1x10(-4) and 4.2x10(-5), respectively. Our data provide the basis for the most accurate genetic risk calculations, as well as new insights on the evolution of the SMN region, with evidence that nucleotide position 840 ( where a transition 840C>T functionally distinguishes SMN2 from SMN1) constitutes a mutation hotspot. Our data also suggest selection of the 1-1 haplotype and the presence of rare chromosomes with three copies of SMN1. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Natl Canc Inst, Human Genet Sect, Lab Gen Divers, Frederick, MD USA. RP Ogino, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu NR 45 TC 46 Z9 53 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD DEC PY 2004 VL 12 IS 12 BP 1015 EP 1023 DI 10.1038/sj.ejhg.5201288 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 871VR UT WOS:000225165200006 PM 15470363 ER PT J AU Weiss, T Miltner, WHR Liepert, J Meissner, W Taub, E AF Weiss, T Miltner, WHR Liepert, J Meissner, W Taub, E TI Rapid functional plasticity in the primary somatomotor cortex and perceptual changes after nerve block SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Review DE human; magnetic source imaging; magnetoencephalography; transcranial magnetic stimulation ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; PHANTOM-LIMB PAIN; PRIMARY SOMATOSENSORY CORTEX; AMYOTROPHIC-LATERAL-SCLEROSIS; TACTILE SPATIAL-RESOLUTION; INDUCED MOVEMENT THERAPY; SHORT-TERM PLASTICITY; SPINAL-CORD-INJURY; CORTICAL REORGANIZATION AB The mature human primary somatosensory cortex displays a striking plastic capacity to reorganize itself in response to changes in sensory input. Following the elimination of afferent return, produced by either amputation, deafferentation by dorsal rhizotomy, or nerve block, there is a well-known but little-understood 'invasion' of the deafferented region of the brain by the cortical representation zones of still-intact portions of the brain adjacent to it. We report here that within an hour of abolishing sensation from the radial and medial three-quarters of the hand by pharmacological blockade of the radial and median nerves, magnetic source imaging showed that the cortical representation of the little finger and the skin beneath the lower lip, whose intact cortical representation zones are adjacent to the deafferented region, had moved closer together, presumably because of their expansion across the deafferented area. A paired-pulse transcranial magnetic stimulation procedure revealed a motor cortex disinhibition for two muscles supplied by the unaffected ulnar nerve. In addition, two notable perceptual changes were observed: increased two-point discrimination ability near the lip and mislocalization of touch of the intact ulnar portion of the fourth finger to the neighbouring third finger whose nerve supply was blocked. We suggest that disinhibition within the somatosensory system as a functional correlate for the known enlargement of cortical representation zones might account for not only the 'invasion' phenomenon, but also for the observed behavioural correlates of the nerve block. C1 Univ Jena, Dept Biol & Clin Psychol, D-07743 Jena, Germany. Univ Jena, Dept Neurol, D-6900 Jena, Germany. Univ Jena, Dept Anaesthesiol & Intens Care Med, D-6900 Jena, Germany. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA. RP Weiss, T (reprint author), Univ Jena, Dept Biol & Clin Psychol, Steiger 3 Haus 1, D-07743 Jena, Germany. EM weiss@biopsy.uni-jena.de NR 121 TC 51 Z9 53 U1 3 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2004 VL 20 IS 12 BP 3413 EP 3423 DI 10.1111/j.1460-9568.2004.03790.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 878ZK UT WOS:000225686000021 PM 15610174 ER PT J AU Verel, I Visser, GWM Vosjan, MJWD Finn, R Boellaard, R van Dongen, GAMS AF Verel, I Visser, GWM Vosjan, MJWD Finn, R Boellaard, R van Dongen, GAMS TI High-quality I-124-labelled monoclonal antibodies for use as PET scouting agents prior to I-131-radioimmunotherapy SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE iodine-124; iodine.-131; I-124 regeneration; monoclonal antibody labelling; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; BREAST-CANCER; NUDE-MICE; I-124; RADIOIMMUNOTHERAPY; TUMOR; FRACTION AB Purpose: Monoclonal antibodies (MAbs) labelled with I-124 are an attractive option for quantitative imaging with positron emission tomography (PET) in a scouting procedure prior to I-131-radioimmunotherapy (I-131-RIT). In this study, three important items in the labelling of MAbs with I-124 were introduced to obtain optimal and reproducible product quality: restoration of radiation-induced inorganic deterioration of the starting I-124 solution, radiation protection during and after I-124 labelling, and synchronisation of the I/MAb molar ratio. Methods: A new method was applied, using all NaIO3/ NaI carrier mix. realising in one step >90% restoration of deteriorated I-124 into the iodide form and chemical control over the I/MAb molar ratio. Chimeric MAb (cMAb) U36 and the murine MAbs 425 and E48 were labelled with I-124 using the so-called Iodogen-coated MAb method, as this method provides optimal quality conjugates under challenging radiation conditions. As a standardising condition, NaIO3/NaI carrier mix was added at a stoichiometric I/MAb molar ratio of 0.9. For comparison, MAbs were labelled with I-131 and with a mixture of I-124, I-123, I-126 and I-130. Results: Labelling with 1241 ill this setting resulted in overall yields of >70%, a radiochemical purity of >95%, and preservation of MAb integrity and immunoreactivity, including at the patient dose level (85 MBq). No significant quality differences were observed when compared with I-131 products. while the iodine isotope mixture gave exactly the same labelling efficiency for each of the isotopes, excluding a different chemical reactivity of I-124-iodide. The scouting performance of I-124-cMAb U36 labelled at the patient dose level was evaluated in biodistribution studies upon co-injection with I-131-labelled cMAb U36. and by PET imaging in nude mice bearing the head and neck cancer xenograft line, HNX-OE. I-124-cMAb and I-131-cMAb U36 labelled with a synchronised I/MAb molar ratio gave fully concordant tissue uptake values. Selective tumour uptake was confirmed with immuno-PET. revealing visualisation of 15 out of 15 tumours. Conclusion: These results pave the way for renewed evaluation of the potential of I-124-immuno-PET for clinical applications. C1 VU Univ Med Ctr, Dept Otolaryngol Head & Neck Surg, NL-1007 MB Amsterdam, Netherlands. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. VU Univ Med Ctr, Radionuclide Ctr, Amsterdam, Netherlands. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. VU Univ Med Ctr, PET Ctr, Amsterdam, Netherlands. RP van Dongen, GAMS (reprint author), VU Univ Med Ctr, Dept Otolaryngol Head & Neck Surg, De Boelelaan 1117,POB 7057, NL-1007 MB Amsterdam, Netherlands. EM gams.vandongen@vumc.nl OI Boellaard, Ronald/0000-0002-0313-5686 NR 26 TC 35 Z9 37 U1 3 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD DEC PY 2004 VL 31 IS 12 BP 1645 EP 1652 DI 10.1007/s00259-004-1632-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 882JX UT WOS:000225936300013 PM 15290121 ER PT J AU Trisini, AT Singh, NP Duty, SM Hauser, R AF Trisini, AT Singh, NP Duty, SM Hauser, R TI Relationship between human semen parameters and deoxyribonucleic acid damage assessed by the neutral comet assay SO FERTILITY AND STERILITY LA English DT Article DE comet assay; DNA integrity; microgel electrophoresis; sperm ID DNA STRAND BREAKS; CHROMATIN-STRUCTURE ASSAY; EJACULATED HUMAN SPERMATOZOA; FERTILIZATION IN-VITRO; HUMAN SPERM; OXIDATIVE STRESS; UNEXPLAINED INFERTILITY; HUMAN-FERTILITY; FRAGMENTATION; INTEGRITY AB Objective: To explore the association between semen parameters and sperm DNA damage. Design: Cross-sectional. Setting: Andrology clinic. Patient(s): Two hundred fifty-seven men undergoing infertility assessment. Intervention(s): None. Main Outcome Measure(s): Sperm concentration and motility were measured using computer-assisted sperm analysis; morphology was scored using the strict criteria. The neutral comet assay was used to measure sperm DNA damage. Comet assay parameters included comet extent, percent DNA in the comet tail, and tail distributed moment, an integrated measure of length and intensity. We also scored cells that were too long to measure (>300 mum), which we referred to as cells with high DNA damage. Result(s): Men older than 35 years had a statistically significant increase in the number of cells with high DNA damage as compared with younger men. In age-adjusted regression analyses, the most consistent associations were found between semen parameters and the number of cells with high DNA damage. For an interquartile range change in the number of cells with high DNA damage, sperm concentration declined 14.2 x 10(6)/mL, motility declined 4.3%, and morphology declined 0.5%. Comet extent and percent DNA in the comet tail were also associated with a decline in sperm concentration and motility, respectively. Conclusion(s): Although there were associations between semen and comet assay parameters, their magnitudes were weak, suggesting that the comet assay provides additional independent information on sperm function. (C) 2004 by American Society for Reproductive Medicine. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu FU NIEHS NIH HHS [ES09718, ES00002] NR 40 TC 50 Z9 61 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 2004 VL 82 IS 6 BP 1623 EP 1632 DI 10.1016/j.fertnstert.2004.05.087 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 880PS UT WOS:000225802300023 PM 15589869 ER PT J AU Won, JS Im, YB Singh, AK Singh, I AF Won, JS Im, YB Singh, AK Singh, I TI Dual role of cAMP in iNOS expression in glial cells and macrophages is mediated by differential regulation of p38-MAPK/ATF-2 activation and iNOS stability SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ATF-2; p38-MAPK; iNOS; proteasome; cAMP; forskolin; glial cells; macrophages; free radicals ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; RAT MESANGIAL CELLS; CYCLIC-AMP; GENE-EXPRESSION; PROTEIN-KINASE; BINDING-PROTEIN; TRANSCRIPTION AB We reported previously that cAMP analogues or cAMP synthesis activator (forskolin; FSK) inhibit lipopolysaccharide (LPS)-induced inducible nitric-oxide systase (NOS) gene expression in astrocytes, while they enhance that in macrophages. Here, we report that the FSK-mediated inhibition of iNOS expression in C6 glial cells is due to its reduced transcriptional activity, while the FSK-mediated enhancement of iNOS expression in RAW264.7 macrophages is a result of increased stability of iNOS protein without transcriptional enhancement. The LPS/interferon-gamma (IFN)-induced iNOS transcription was inhibited by FSK via inhibition of p38-MAPK/ATF-2 activity in glial cells while it was not affected in macrophages. In both cell types, proteasome activities were required for the spontaneous degradation of NOS protein, and the inhibition of proteasome activity by MG132 after maximum increase of iNOS protein levels further enhanced iNOS protein induction by LPS/IFN, suggesting the involvement of proteasome in iNOS degradation. More importantly, the iNOS protein levels were equalized by the MG132 posttreatment in macrophages treated with LPS/IFN alone and along with FSK, and ubiquitinated iNOS protein levels were reduced by FSK posttreatment, suggesting that the FSK-mediated inhibition of ubiquitination of NOS protein and the following increased stability of iNOS protein are one of the mechanisms of cAMP-pathway-mediated enhancement of iNOS gene expression in macrophages. To our knowledge, this is the first evidence that cAMP regulates NOS expression at the posttranslational level in macrophages. (C) 2004 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, Div Dev Neurogenet, 316 CSB, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-37766, NS-34741, NS-40810] NR 46 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 1 PY 2004 VL 37 IS 11 BP 1834 EP 1844 DI 10.1016/j.freeradbiomed.2004.08.017 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 874RC UT WOS:000225366500016 PM 15528042 ER PT J AU Podolsky, DK AF Podolsky, DK TI American Gastroenterological Association - Presidential address SO GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2004 VL 127 IS 6 BP 1838 EP 1840 DI 10.1053/j.gastro.2004.10.037 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 879OV UT WOS:000225728000024 PM 15578521 ER PT J AU Khalid, A Finkelstein, S McGrath, K AF Khalid, A Finkelstein, S McGrath, K TI Molecular diagnosis of solid and cystic lesions of the pancreas SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID K-RAS MUTATIONS; DETECTING TELOMERASE ACTIVITY; POLYMERASE-CHAIN-REACTION; INTRAEPITHELIAL NEOPLASIA; DUCTAL ADENOCARCINOMA; GENE-MUTATIONS; PREOPERATIVE DIAGNOSIS; BRUSH CYTOLOGY; IMMUNOHISTOCHEMICAL EVALUATION; HER-2/NEU EXPRESSION AB Pancreatic cancer is associated with a poor prognosis, and long-term survival has not changed significantly over the last several decades. Significant efforts are focused on improved diagnosis and earlier detection of pancreatic cancer through identification of specific biomarkers. This article reviews clinical applications of molecular diagnosis of solid and cystic pancreatic neoplasia. C1 Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. Univ Dr, Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA 15213 USA. RP McGrath, K (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, M2,C Wing,A6163,200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcgrathkm@upmc.edu NR 86 TC 8 Z9 8 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD DEC PY 2004 VL 33 IS 4 BP 891 EP + DI 10.1016/j.gtc.2004.07.007 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 873SZ UT WOS:000225302600012 PM 15528024 ER PT J AU Farrell, JJ Garber, J Sahani, D Brugge, WR AF Farrell, JJ Garber, J Sahani, D Brugge, WR TI EUS findings in patients with autoimmune pancreatitis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy/Digestive Disease Week 2003 CY MAY 18-21, 2003 CL ORLANDO, FL SP Amer Soc Gastrointestinal Endoscopy ID FINE-NEEDLE-ASPIRATION; LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; ENDOSCOPIC ULTRASOUND; PREOPERATIVE ASSESSMENT; STEROID-THERAPY; CARCINOMA; MASSES; CHOLANGITIS; CANCER; CT AB Background: Autoimmune pancreatitis is an increasingly recognized benign condition with a presentation similar to pancreatic neoplasia but responds to corticosteroid therapy. Clinical features, ERCP, and CT findings have been described. This study assessed the EUS and EUS-guided FNA features of proven autoimmune pancreatitis. Methods: The diagnosis of autoimmune pancreatitis was based on examination of surgical resection specimens or typical clinical findings (elevated immunoglobulin G level, no evidence of malignancy, characteristic non-EUS imaging studies, and clinical improvement, especially in response to treatment with a corticosteroid). Results: Presenting manifestations in 14 patients included obstructive jaundice, abdominal pain, and weight loss. Ten patients underwent surgery (including exploratory surgery). Six were successfully treated with corticosteroid. EUS revealed diffuse hypoechoic pancreatic enlargement (8/14) or a focal irregular hypoechoic mass (6/14). Features of chronic pancreatitis were not noted. EUS-guided FNA of the pancreas was suggestive of chronic inflammatory pancreatitis in 9 of 12 patients. Celiac and peripancreatic lymphadenopathy (up to 3 cm in diameter) was present in 6 patients. EUS-guided FNA of lymph nodes (3/4) did not reveal evidence of malignancy. Vascular involvement was noted in 3 patients. Conclusions: The EUS features of autoimmune pancreatitis are easily mistaken for malignancy. However, a diffusely hypoechoic, enlarged pancreas, together with chronic inflammatory cells in aspirated cytologic specimens, is supportive of the diagnosis of autoimmune pancreatitis. When combined with clinical data, EUS and EUS-guided FNA may support a diagnosis of autoimmune pancreatitis, may warrant a trial of corticosteroid, and thereby may prevent unnecessary surgery. C1 Univ Calif Los Angeles, Ctr Hlth Sci, Div Digest Dis, Sch Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Gastrointestinal Unit,Div Abdominal Imaging & Int, Boston, MA USA. RP Farrell, JJ (reprint author), Univ Calif Los Angeles, Ctr Hlth Sci, Div Digest Dis, Sch Med, Los Angeles, CA 90095 USA. NR 40 TC 83 Z9 90 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD DEC PY 2004 VL 60 IS 6 BP 927 EP 936 AR PII S0016-5107(04)02230-8 DI 10.1016/S0016-5107(04)02230-8 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 883NI UT WOS:000226019200011 PM 15605008 ER PT J AU Hieronymus, H Silver, PA AF Hieronymus, H Silver, PA TI A systems view of mRNP biology SO GENES & DEVELOPMENT LA English DT Review DE systems biology; messenger ribonucleoprotein complexes; mRNP; genomics; mRNA decay; mRNA transport; translation; splicing ID GENOME-WIDE ANALYSIS; MESSENGER-RNA EXPORT; PROTEIN-PROTEIN INTERACTIONS; IRON-REGULATORY PROTEINS; IN-VIVO KINETICS; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; GENE-EXPRESSION; GLOBAL ANALYSIS; NUCLEAR-PORE AB Gene expression occurs through a complex mRNA-protein (mRNP) system that stretches from transcription to translation. Gene expression processes are increasingly studied from global perspectives in order to understand their pathways, properties, and behaviors as a system. Here we review these beginnings of mRNP systems biology, as they have emerged from recent large-scale investigation of mRNP components, interactions, and dynamics. Such work has begun to lay the foundation for a broader, integrated view of mRNP organization in gene expression. C1 Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. EM Pamela_silver@dfci.harvard.edu NR 144 TC 115 Z9 121 U1 1 U2 10 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 DEC 1 PY 2004 VL 18 IS 23 BP 2845 EP 2860 DI 10.1101/gad.1256904 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 877EH UT WOS:000225550100002 PM 15574591 ER PT J AU Mehle, A Goncalves, J Santa-Marta, M McPike, M Gabuzda, D AF Mehle, A Goncalves, J Santa-Marta, M McPike, M Gabuzda, D TI Phosphorylation of a novel SOCS-box regulates assembly of the HIV-1 Vif-Cul5 complex that promotes APOBEC3G degradation SO GENES & DEVELOPMENT LA English DT Article DE Cullin; SOCS-box; BC-box; HIV; Vif; APOBEC3G ID VIF PROTEIN; ANTIVIRAL ACTIVITY; ENZYME APOBEC3G; ACTIVATION; PROTEASOME; BINDS; DNA; UBIQUITINATION; RECONSTITUTE; RECOGNITION AB HIV-1 Vif (viral infectivity factor) protein overcomes the antiviral activity of the DNA deaminase APOBEC3G by targeting it for proteasomal degradation. We report here that Vif targets APOBEC3G for degradation by forming an SCF-like E3 ubiquitin ligase containing Cullin 5 and Elongins B and C (Cul5-EloB-EloC) through a novel SOCS (suppressor of cytokine signaling)-box that binds EloC. Vif binding to EloC is negatively regulated by serine phosphorylation in the BC-box motif of the SOCS-box. Vif ubiquitination is promoted by Cul5 in vitro and in vivo, and requires an intact SOCS-box. Thus, auto-ubiquitination of Vif occurs within the assembled Vif-Cul5 complex, analogous to F-box proteins that are autoubiquitinated within their SCF (Skp1-Cullin-F-box) complex. These findings suggest mechanisms that regulate the assembly and activity of Cul5 E3 complexes through phosphorylation or autoubiquitination of the SOCS-box protein, and identify interactions between Vif and host cell proteins that may be therapeutic targets. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Lisbon, Fac Farm, Ctr Patogenese Mol, URIA, P-1649019 Lisbon, Portugal. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Santa-Marta, Mariana/L-2407-2013; iMed.ULisboa, iMed.ULisboa/C-6292-2014; Goncalves, Joao/B-2013-2008; iMed.ULisboa, M2B /B-5277-2014 OI Santa-Marta, Mariana/0000-0002-0243-4158; Goncalves, Joao/0000-0002-1245-3715; FU NIAID NIH HHS [AI 36186, AI 62555, R01 AI062555] NR 33 TC 218 Z9 225 U1 0 U2 3 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 DEC 1 PY 2004 VL 18 IS 23 BP 2861 EP 2866 DI 10.1101/gad.1249904 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 877EH UT WOS:000225550100003 PM 15574592 ER PT J AU Brugarolas, J Lei, K Hurley, RL Manning, BD Reiling, JH Hafen, E Witter, LA Ellisen, LW Kaelin, WG AF Brugarolas, J Lei, K Hurley, RL Manning, BD Reiling, JH Hafen, E Witter, LA Ellisen, LW Kaelin, WG TI Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex SO GENES & DEVELOPMENT LA English DT Article DE tuberous sclerosis complex; TSC1; TSC2; REDD1/RTP801; mTOR; hypoxia ID TUBEROUS SCLEROSIS COMPLEX; ACTIVATED PROTEIN-KINASE; CELL-GROWTH; MAMMALIAN TARGET; 3-KINASE/AKT PATHWAY; GENE-PRODUCTS; UP-REGULATION; TSC2; RHEB; RAPAMYCIN AB Mammalian target of rapamycin (mTOR) is a central regulator of protein synthesis whose activity is modulated by a variety of signals. Energy depletion and hypoxia result in mTOR inhibition. While energy depletion inhibits mTOR through a process involving the activation of AMP-activated protein kinase (AMPK) by LKB1 and subsequent phosphorylation of TSC2, the mechanism of mTOR inhibition by hypoxia is not known. Here we show that mTOR inhibition by hypoxia requires the TSC1/TSC2 tumor suppressor complex and the hypoxia-inducible gene REDD1/RTP801. Disruption of the TSC1/TSC2 complex through loss of TSC1 or TSC2 blocks the effects of hypoxia on mTOR, as measured by changes in the mTOR targets S6K and 4E-BP1, and results in abnormal accumulation of Hypoxia-inducible factor (HIF). In contrast to energy depletion, mTOR inhibition by hypoxia does not require AMPK or LKB1. Down-regulation of mTOR activity by hypoxia requires de novo mRNA synthesis and correlates with increased expression of the hypoxia-inducible REDD1 gene. Disruption of REDD1 abrogates the hypoxia-induced inhibition of mTOR, and REDD1 overexpression is sufficient to down-regulate S6K phosphorylation in a TSC1/TSC2-dependent manner. Inhibition of mTOR function by hypoxia is likely to be important for tumor suppression as TSC2-deficient cells maintain abnormally high levels of cell proliferation under hypoxia. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02116 USA. Dartmouth Coll, Dept Med & Biochem, Dartmouth Med Sch, Hanover, NH 03755 USA. Dartmouth Coll, Dept Sci Biol, Hanover, NH 03755 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Univ Zurich, Inst Zool, CH-8057 Zurich, Switzerland. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu FU NCI NIH HHS [R01 CA122589]; NIDDK NIH HHS [DK 35712, R01 DK035712] NR 53 TC 642 Z9 669 U1 7 U2 31 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 DEC 1 PY 2004 VL 18 IS 23 BP 2893 EP 2904 DI 10.1101/gad.1256804 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 877EH UT WOS:000225550100007 PM 15545625 ER PT J AU Goldstein, DP Garner, EIO Feltmate, CM Berkowitz, RS AF Goldstein, DP Garner, EIO Feltmate, CM Berkowitz, RS TI The role of repeat uterine evacuation in the management of persistent gestational trophoblastic disease SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID FOLINIC ACID; LOW-RISK; TUMORS; WOMEN; CHEMOTHERAPY; METHOTREXATE; EXPERIENCE C1 Harvard Univ, Sch Med,Gillette Ctr Womens Canc,Trophoblast Tumo, Dana Farber Canc Inst,Div Gynecol Oncol,New Engla, Brigham & Womens Hosp,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med,Gillette Ctr Womens Canc,Trophoblast Tumo, Dana Farber Canc Inst,Div Gynecol Oncol,New Engla, Brigham & Womens Hosp,Dept Obstet & Gynecol, 44 Binney St, Boston, MA 02115 USA. EM Ross_Berkowitz@dfci.harvard.edu NR 8 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2004 VL 95 IS 3 BP 421 EP 422 DI 10.1016/j.ygyno.2004.10.022 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 880NK UT WOS:000225796300001 PM 15581941 ER PT J AU Horowitz, NS Dehdashti, F Herzog, TJ Rader, JS Powell, MA Gibb, RK Grigsby, PW Siegel, BA Mutch, DG AF Horowitz, NS Dehdashti, F Herzog, TJ Rader, JS Powell, MA Gibb, RK Grigsby, PW Siegel, BA Mutch, DG TI Prospective evaluation of FDG-PET for detecting pelvic and para-aortic lymph node metastasis in uterine corpus cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE FDG-PET; uterine corpus cancer; lymph node metastasis ID POSITRON-EMISSION-TOMOGRAPHY; ENDOMETRIAL CANCER; CERVICAL-CANCER; CARCINOMA; ADENOCARCINOMA; SURVEILLANCE; SURVIVAL; SARCOMA; PATTERN AB Objectives. To estimate the sensitivity and specificity of positron emission tomography (PET) with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for detecting pelvic and para-aortic lymph node metastasis in patients with uterine corpus carcinoma before surgical staging. Methods. Patients with newly diagnosed FIGO grade 2 or 3 endometrioid, papillary serous, or clear cell adenocarcinoma or uterine corpus sarcoma scheduled for surgical staging, including bilateral pelvic and para-aortic lymphadenectomy, were eligible. PET was performed within 30 days of surgery and interpreted independently by two nuclear medicine physicians. The imaging, operative, and pathologic findings for each patient and each nodal site were compared, and the sensitivity and specificity of FDG-PET in predicting nodal metastasis were determined. Results. Twenty patients underwent FDG-PET before surgical staging. One patient found to have ovarian carcinoma on final pathology was excluded. Of the 19 primary intrauterine tumors, 16 (84%) exhibited increased FDG uptake. One patient did not undergo lymphadenectomy; her chest CT was suspicious for metastatic disease and FDG-PET showed uptake in multiple nodal and pulmonary foci. Metastatic disease was confirmed by percutaneous nodal biopsy. A total of three pathologically positive nodes were found in 2 of the 18 patients (11%). FDG-PET predicted that 3 patients would have positive lymph nodes (2 true positive and 1 false positive). Analyzed by lymph node regions, FDG-PET had 60% sensitivity and 98% specificity. The sensitivity and specificity by individual patient were 67% and 94%, respectively. Conclusions. FDG-PET is only moderately sensitive in predicting lymph node metastasis pre-operatively in patients with endometrial cancer. This imaging modality should not replace lymphadenectomy, but may be helpful for patients in whom lymphadenectomy cannot be, or was not, performed. (C) 2004 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Div Gynecol Oncol, Dept Obstet, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Gynecol Oncol, Dept Gynecol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Radiol, Div Nucl Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. RP Horowitz, NS (reprint author), Massachusetts Gen Hosp, Gillette Canc Ctr, 55 Fruit St,Cox Bldg,5th Floor, Boston, MA 02114 USA. EM nhorowitz@partners.org NR 26 TC 97 Z9 100 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2004 VL 95 IS 3 BP 546 EP 551 DI 10.1016/j.ygyno.2004.08.009 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 880NK UT WOS:000225796300021 PM 15581961 ER PT J AU Berkenblit, A Seiden, MV Matulonis, UA Penson, RT Krasner, CN Roche, M Mezzetti, L Atkinson, T Cannistra, SA AF Berkenblit, A Seiden, MV Matulonis, UA Penson, RT Krasner, CN Roche, M Mezzetti, L Atkinson, T Cannistra, SA TI A phase II trial of weekly docetaxel in patients with platinum-resistant epithelial ovarian, primary peritoneal serous cancer, or fallopian tube cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; CANALICULAR STENOSIS SECONDARY; GYNECOLOGIC-ONCOLOGY-GROUP; CARCINOMA CELL-LINES; PACLITAXEL; RECURRENT; TAXOTERE; CISPLATIN; AGENT; TAXOL AB Objective. To determine the activity and tolerability of weekly docetaxel in patients with platinum-resistant mullerian origin tumors. Methods. Patients with persistent disease, or those recurring less than 6 months after receiving platinum-containing therapy, were eligible for this phase II study. Docetaxel was initially administered at a dose of 40 mg/m(2) on days 1, 8, and 15, with a cycle length of 28 days. This starting dose was subsequently reduced to 30 mg/m(2) due to toxicity. Dexamethasone prophylaxis was administered at a dose of 4 mg PO every 12 hours for 3 doses, starting 12 hours before each dose of docetaxel. Results. Thirty-two patients were enrolled, with a median age of 59 years. The majority of patients received a median of 3 prior regimens, with 45% of the study group having received 4 or more prior regimens. The overall response rate in 29 evaluable patients was 6.9%, with no complete responses. Seventeen percent of patients experienced stable disease. Dose reduction or delay was required in 10 of the first 22 patients enrolled, prompting a reduction in the starting dose to 30 mg/m(2). Hematologic toxicity was generally tolerable, and no patient experienced febrile neutropenia. Non-hematologic toxicity was generally grade I in nature, although a combination of multiple low grade toxicities occurring in an individual patient oftentimes mandated dose reduction. Conclusions. Weekly docetaxel demonstrated modest activity in a heavily pre-treated, platinum-resistant population. A starting docetaxel dose of 30 mg/m(2) would be reasonable for future studies exploring the utility of weekly dosing in less heavily pre-treated patients. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Dana Farber Canc Ctr, Program Gynecol Oncol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Dana Farber Canc Ctr, Program Gynecol Oncol, Boston, MA 02215 USA. Harvard Univ, Dana Farber Canc Inst, Dana Farber Canc Ctr, Program Gynecol Oncol, Boston, MA 02215 USA. RP Cannistra, SA (reprint author), Beth Israel Deaconess Med Ctr, Program Gynecol Med Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM scannist@bidmc.harvard.edu NR 37 TC 29 Z9 29 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2004 VL 95 IS 3 BP 624 EP 631 DI 10.1016/j.ygyno.2004.08.028 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 880NK UT WOS:000225796300034 PM 15581974 ER PT J AU Barata, JT Keenan, TD Silva, A Nadler, LM Boussiotis, VA Cardoso, AA AF Barata, JT Keenan, TD Silva, A Nadler, LM Boussiotis, VA Cardoso, AA TI Common gamma chain-signaling cytokines promote proliferation of T-cell acute lymphoblastic leukemia SO HAEMATOLOGICA LA English DT Article DE T-ALL; IL-7; common gamma chain; proliferation ID THYMIC LYMPHOMAS; PROGENITOR CELLS; TRANSGENIC MICE; INTERLEUKIN-2 RECEPTORS; FACTOR REQUIREMENTS; NATURAL-KILLER; GROWTH-FACTOR; EXPRESSION; THYMOCYTES; IL-7 AB Background and Objectives. The identification of signals critical for the pathophysiology of T-cell acute lymphoblastic leukemia (T-ALL) should contribute to the development of novel, more effective therapeutic strategies. Common gamma-chain signaling cytokines (gamma c-cytokines) - interleukins 2, 4, 7, 9 and 15 - differentially regulate T-cell development, survival, proliferation and differentiation. Although studies exist on some individual cytokines, no comprehensive analysis of the effects of the gamma c-cytokine family on malignant T cells has been reported. Here, we examined the effect of gamma c-cytokines on T-ALL proliferation. Design and Methods. Primary leukemic cells were collected at diagnosis from the blood or bone marrow of children with T-ALL. The cells were immunophenotyped and classified according to maturation stage. Proliferative responses to gamma c-cytokines were assessed by H-3-thymidine incorporation. Results. All gamma c-cytokines promoted proliferation of primary T-ALL cells. Interleukin (IL)-7 was the cytokine that most frequently induced leukemic cell proliferation and promoted the most robust responses. IL-4 preferentially stimulated proliferation of samples with a more mature immunophenotype, whereas CD1a-positive cortical T-ALL cells were less responsive to IL-9. Finally, combinations of two gamma c-cytokines showed synergistic or additive proliferative effects. Interpretation and Conclusions. This study indicates that all the gamma c-cytokines tested can stimulate proliferation of leukemic T cells and suggests that synergistic effects may occur in vivo. We present the first demonstration that IL-9 and IL-15 can provide a proliferative signal to T-ALL cells. Importantly, our results support the hypothesis that IL-7 may function as a critical regulator of T-ALL and that its activity may be potentiated by other,gamma c-cytokines. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Lisbon, Sch Med, Inst Mol Med, P-1699 Lisbon, Portugal. RP Cardoso, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Room D-540B,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu RI Barata, Joao/D-9181-2015 OI Barata, Joao/0000-0002-4826-8976 FU NCI NIH HHS [P01-CA68484] NR 50 TC 25 Z9 26 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD DEC PY 2004 VL 89 IS 12 BP 1459 EP 1467 PG 9 WC Hematology SC Hematology GA 940TG UT WOS:000230166500009 PM 15590396 ER PT J AU Peabody, JW Tozija, F Munoz, JA Nordyke, RJ Luck, J AF Peabody, JW Tozija, F Munoz, JA Nordyke, RJ Luck, J TI Using vignettes to compare the quality of clinical care variation in economically divergent countries SO HEALTH SERVICES RESEARCH LA English DT Article DE benchmarking/methods; quality indicators; health care; quality of health care; cross-national comparative study; clinical vignettes ID PRIMARY-HEALTH-CARE; STANDARDIZED PATIENTS; MEDICAL-RECORD; CHART ABSTRACTION; CASE-MANAGEMENT; SERVICES; VALIDATION; PERCEPTIONS; PERFORMANCE; GUIDELINES AB Objective. To determine whether clinical vignettes can measure variations in the quality of clinical care in two economically divergent countries. Data Source/Study Setting. Primary data collected between February 1997 and February 1998 at two Veterans Affairs facilities in the United States and four government-run outpatient facilities in Macedonia. Study Design. Randomly selected, eligible Macedonian and U.S. physicians (>97 percent participation rate) completed vignettes for four common outpatient conditions. Responses were judged against a master list of explicit quality criteria and scored as percent correct. Data Collection/Extraction. An ANOVA model and two-tailed t-tests were used to compare overall scores by case, study site, and country. Principal Findings. The mean score for U.S. physicians was 67 percent (+/-11 percent) compared to 48 percent (+/-11 percent) for Macedonian physicians. The quality of clinical practice, which emphasizes basic skills, varied greatly in both sites, but more so in Macedonia. However, the top Macedonian physicians in all sites approached or-in one case-exceeded the median score in the U.S. sites. Conclusions. Vignettes are a useful method for making cross-national comparisons of the quality of care provided in very different settings. The vignette measurements revealed that some physicians in Macedonia performed at a standard comparable to that of their counterparts in the United States, despite the disparity of the two health systems. We infer that in poorer countries, policy that promotes improvements in the quality of clinical practice-not just structural inputs-could lead to rapid improvements in health. C1 Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA 94105 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90406 USA. Univ St Cyril & Methudius, Cathedra Social Med Med Fac, Skopje 91000, Macedonia. Escuela Super Econ & Negocios, San Salvador, El Salvador. Vet Affiars Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, Inst Global Hlth, 74 New Montgomery,Suite 508, San Francisco, CA 94105 USA. NR 53 TC 30 Z9 30 U1 3 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD DEC PY 2004 VL 39 IS 6 BP 1951 EP 1970 DI 10.1111/j.1475-6773.2004.00327.x PN 2 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 893TZ UT WOS:000226743500003 PM 15544639 ER PT J AU Kolodgie, FD Virmani, R Burke, AP Farb, A Weber, DK Kutys, R Finn, AV Gold, HK AF Kolodgie, FD Virmani, R Burke, AP Farb, A Weber, DK Kutys, R Finn, AV Gold, HK TI Pathologic assessment of the vulnerable human coronary plaque SO HEART LA English DT Article ID RISK-FACTORS; DEATH; PROGRESSION; THROMBOSIS; CHOLESTEROL; ATHEROMA; STATINS; EROSION; DISEASE; RUPTURE C1 Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. RP Virmani, R (reprint author), Armed Forces Inst Pathol, Dept Cardiovasc Pathol, 6825 16th St NW, Washington, DC 20306 USA. EM virmani@afip.osd.mil FU NHLBI NIH HHS [R01 HL61799-02] NR 14 TC 218 Z9 244 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD DEC PY 2004 VL 90 IS 12 BP 1385 EP 1391 DI 10.1136/hrt.2004.041798 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 871VA UT WOS:000225162700006 PM 15547008 ER PT J AU Achenbach, S Sacher, D Ropers, D Pohle, K Nixdorff, U Hoffmann, U Muschiol, G Flachskampf, FA Daniel, WG AF Achenbach, S Sacher, D Ropers, D Pohle, K Nixdorff, U Hoffmann, U Muschiol, G Flachskampf, FA Daniel, WG TI Electron beam computed tomography for the detection of left atrial thrombi in patients with atrial fibrillation SO HEART LA English DT Editorial Material ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY C1 Univ Erlangen Nurnberg, Dept Internal Med Cardiol 2, D-91054 Erlangen, Germany. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Achenbach, S (reprint author), Univ Erlangen Nurnberg, Dept Internal Med 2, Ulmenweg 18, D-91054 Erlangen, Germany. EM stephan.achenbach@med2.med.uni-erlangen.de NR 5 TC 21 Z9 22 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD DEC PY 2004 VL 90 IS 12 BP 1477 EP 1478 DI 10.1136/hrt.2003.027805 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 871VA UT WOS:000225162700025 PM 15547034 ER PT J AU Ellinor, PT Moore, RK Patton, KK Ruskin, JN Pollak, MR MacRae, CA AF Ellinor, PT Moore, RK Patton, KK Ruskin, JN Pollak, MR MacRae, CA TI Mutations in the long QT gene, KCNQ1, are an uncommon cause of atrial fibrillation SO HEART LA English DT Editorial Material ID LOCUS C1 Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM cmacrae@partners.org RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 FU NHLBI NIH HHS [HL71632, K23 HL071632, R01 HL075431] NR 5 TC 50 Z9 50 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD DEC PY 2004 VL 90 IS 12 BP 1487 EP 1488 DI 10.1136/hrt.2003.027227 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 871VA UT WOS:000225162700030 PM 15547041 ER PT J AU Patton, K Reddy, VY AF Patton, K Reddy, VY TI Optimizing the defibrillation vector with a right-sided implantable cardioverter-defibrillator SO HEART RHYTHM LA English DT Editorial Material C1 Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD DEC PY 2004 VL 1 IS 6 BP 756 EP 756 DI 10.1016/j.hrthm.2004.08.014 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RJ UT WOS:000226809000020 PM 15851253 ER PT J AU Valverde, AM Fabregat, I Burks, DJ White, MF Benito, M AF Valverde, AM Fabregat, I Burks, DJ White, MF Benito, M TI IRS-2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes SO HEPATOLOGY LA English DT Article ID GROWTH-FACTOR-I; FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE B; PHOSPHATIDYLINOSITOL 3-KINASE; BROWN ADIPOCYTES; CELL-SURVIVAL; FACTOR-BETA; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; INDUCED APOPTOSIS AB To assess the role of insulin action and inaction in the liver, immortalized hepatocyte cell lines have been generated from insulin receptor substrate (IRS)-2(-/-) and wild-type mice. Using this model, we have recently demonstrated that the lack of IRS-2 in neonatal hepatocytes resulted in insulin resistance. In the current study, we show that immortalized neonatal hepatocytes undergo apoptosis on serum withdrawal, with caspase-3 activation and DNA laddering occurring earlier in the absence of IRS-2. Insulin rescued wild-type hepatocytes from serum withdrawal-induced caspase-3 activation and DNA fragmentation in a dose-dependent manner, but it failed to rescue hepatocytes lacking IRS-2. In IRS-2(-/-) cells, insulin failed to phosphorylate Bad. Furthermore in these cells, insulin was unable to translocate Foxo1 from the nucleus to the cytosol. Adenoviral infection of wild-type cells with constitutively active Foxo1 (ADA) induced caspase-8 and caspase-3 activities, proapoptotic gene expression, DNA laddering and apoptosis. Dominant negative Foxo1 regulated the whole pathway in an opposite manner. Prolonged insulin treatment (24 hours) increased expression of antiapoptotic genes (Bcl-x(L)), downregulated. proapoptotic genes (Bim and nuclear Foxo1), and decreased caspase-3 activity in wild-type hepatocytes but not in IRS-2(-/-) cells. Infection of IRS-2(-/-) hepatocytes with adenovirus encoding IRS-2 reconstituted phosphatidylinositol 3-kinase (PI 3-kinase)/Akt/Foxo1 signaling, restored pro- and antiapoptotic gene expression, and decreased caspase-3 activity in response to insulin, thereby blocking apoptosis. In conclusion, IRS-2 signaling is specifically required through PIP3 generation to mediate the survival effects of insulin. Epidermal growth factor, via PIP3/Akt/Foxo1 phosphorylation, was able to rescue IRS-2(-/-) hepatocytes from serum withdrawal-induced apoptosis, modulating pro- and anti-apoptotic gene expression and downregulating caspase-3 activity. C1 Univ Complutense, Inst Bioquim, Dept Bioquim & Biol Mol 2, Ctr Mixto,CSIC,UCM,Fac Farm, E-28040 Madrid, Spain. Fac Med, Dept Anat, Salamanca, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Valverde, AM (reprint author), Inst Bioquim, Dept Bioquim & Biol Mol, Fac Farm, Ciudad Univ, Madrid 28040, Spain. EM valverde@farm.ucm.es RI Benito, Manuel/J-5637-2014 OI Benito, Manuel/0000-0002-7218-406X NR 50 TC 37 Z9 42 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2004 VL 40 IS 6 BP 1285 EP 1294 DI 10.1002/hep.20485 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 877PZ UT WOS:000225583800009 PM 15565601 ER PT J AU Jowers, C Shih, R James, J Deloughery, TG Holden, WE AF Jowers, C Shih, R James, J Deloughery, TG Holden, WE TI Effects of Ginkgo biloba on exhaled nasal nitric oxide during normobaric hypoxia in humans SO HIGH ALTITUDE MEDICINE & BIOLOGY LA English DT Article DE vasodilation; acute mountain sickness; high altitude pulmonary edema; nose; altitude ID ACUTE MOUNTAIN-SICKNESS; EXTRACT AB Jowers, Casey, Richard Shih, Jim James, Thomas Deloughery, and William Holden. Effects of Ginkgo biloba on exhaled nasal nitric oxide during normobaric hypoxia in humans. High Alt. Med. Biol. 5:445-449, 2004.-Ginkgo biloba, an extract of the ginkgo tree, may prevent or lessen symptoms of acute mountain sickness in humans. The mechanism of this effect is poorly understood. One hypothesis is that ginkgo alters nitric oxide (NO) metabolism, possibly by scavenging NO or altering nitric oxide synthase expression and thereby lessening the vasodilatory effects of NO. To date, an effect of Ginkgo biloba on NO metabolism has not been demonstrated in humans. We measured exhaled nasal NO output in humans (n = 9) during normoxia and then during acute normobaric hypoxia (goal oxyhemoglobin saturation 75% to 85%) before and after administration of a standardized extract of Ginkgo biloba (120 mg twice daily for 5 days). Oxygen saturation, heart rate, and minute ventilation were similar before and after Ginkgo biloba administration. Exhaled nasal NO output was increased during normoxia following ginkgo (p < 0.02) and reduced during normobaric hypoxia both before (p < 0.02) and following (p < 0.003) ginkgo. Exhaled nasal NO output during normobaric hypoxia was lowest following ginkgo (p < 0.003). We conclude that Ginkgo biloba increases exhaled nasal NO output during normoxia and enhances reduced exhaled nasal NO output during normobaric hypoxia. Our results suggest that Ginkgo biloba may act to reduce AMS through an effect on NO metabolism. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Holden, WE (reprint author), Portland VA Med Ctr, 3710 SW U-S Vet Hosp Rd,P3-PULM, Portland, OR 97201 USA. EM william.holden@med.va.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1527-0297 J9 HIGH ALT MED BIOL JI High Alt. Med. Biol. PD WIN PY 2004 VL 5 IS 4 BP 445 EP 449 DI 10.1089/ham.2004.5.445 PG 5 WC Biophysics; Public, Environmental & Occupational Health; Sport Sciences SC Biophysics; Public, Environmental & Occupational Health; Sport Sciences GA 890GR UT WOS:000226500200007 PM 15671634 ER PT J AU Kim, DE Shin, MJ Lee, KM Chu, K Woo, SH Kim, YR Song, EC Lee, JW Park, SH Roh, JK AF Kim, DE Shin, MJ Lee, KM Chu, K Woo, SH Kim, YR Song, EC Lee, JW Park, SH Roh, JK TI Musical training-induced functional reorganization of the adult brain: Functional magnetic resonance imaging and transcranial magnetic stimulation study on amateur string players SO HUMAN BRAIN MAPPING LA English DT Article DE musical training; fMRI; TMS; string player; brain; plasticity ID ACTIVATION; MUSICIANS; MOVEMENTS; CORTEX; INHIBITION; PERCEPTION; PIANISTS; IMAGERY; SYSTEM; MEMORY AB We used the combined technique of functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to observe changes that occur in adult brains after the practice of stringed musical instruments. We carried out fMRI on eight volunteers (aged 20-22 years): five novices and three individuals who had discontinued practice for more than 5 years. The motor paradigm contained a repetitive lift-abduction/fall-adduction movement of the left/right little finger, carried out with maximum efforts without pacing. The sensory paradigm was to stimulate the same little finger using a string. In parallel to the fMRI acquisition, TMS motor maps for the little finger were obtained using a frameless stereotactic neuronavigation system. After the baseline study, each participant began to learn a stringed instrument. Newly developed fMRI activations for the left little finger were observed 6 months after practice at multiple brain regions including inferior parietal lobule, premotor area (PMA), left precuneus, right anterior superior temporal gyrus, and posterior middle temporal gyrus. In contrast, new activations were rarely observed for the right little finger. The TMS study revealed new motor representation sites for the left little finger in the PMA or supplementary motor area (SMA). Unexpectedly, TMS motor maps for the right little finger were reduced significantly. Among new fMRI activations for sensory stimuli of the left little finger, the cluster of highest activation was located in the SMA. Collectively, these data provide insight into orchestrated reorganization of the sensorimotor and temporal association cortices contributing to the skillful fingering and musical processing after the practice of playing stringed instruments. (C) 2004 Wiley-Liss, Inc. C1 Seoul Natl Univ, Coll Med, Dept Neurol, Seoul 110744, South Korea. Seoul Natl Univ, Interdisciplinary Program Cognit Sci, Dept Neurol, Seoul 110744, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr,Dept Radiol, Boston, MA 02115 USA. Kwandong Univ, Coll Med, Dept Neurol, Kangnung, South Korea. RP Roh, JK (reprint author), Seoul Natl Univ, Coll Med, Dept Neurol, 28 Yongon-Dong, Seoul 110744, South Korea. EM rohjk@snu.ac.kr RI Roh, Jae Kyu/J-5459-2012; Lee, Kyoung Min/J-2775-2012; Park, Seong Ho/J-5488-2012 NR 39 TC 13 Z9 15 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD DEC PY 2004 VL 23 IS 4 BP 188 EP 199 DI 10.1002/hbm.20058 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 871XV UT WOS:000225170800002 PM 15449354 ER PT J AU Browne, TJ Hirsch, MS Brodsky, G Welch, WR Loda, MF Rubin, MA AF Browne, TJ Hirsch, MS Brodsky, G Welch, WR Loda, MF Rubin, MA TI Prospective evaluation of AMACR (P504S) and basal cell markers in the assessment of routine prostate needle biopsy specimens SO HUMAN PATHOLOGY LA English DT Article DE prostate cancer; needle biopsy; alpha-methylacyl-CoA-racemase; P504S; basal cell; immunohistochemistry ID METHYLACYL-COA RACEMASE; ATYPICAL ADENOMATOUS HYPERPLASIA; COENZYME-A RACEMASE; MOLECULAR MARKER; CANCER; DIAGNOSIS; EXPRESSION; BIOMARKER; 34-BETA-E12; CARCINOMA AB Distinguishing benign prostate glands from malignant ones, based purely on morphology, on prostatic core needle biopsy specimens (PNBs) may prove difficult, particularly if the suspicious focus is small. In recent years, several immunohistochemical markers, including the basal cell cocktail (BCC), 34betaE12 and p63, and the prostate cancer (PCa) biomarker alpha-medlylacyl-CoA-racemase (AMACR), have been used as adjuvants to morphology, in these diagnostically challenging cases. We prospectively address the diagnostic utility of using the BCC, in combination with the commercially available AMACR monoclonal antibody, P504S, on PNBs that required immunohistochemistry (IHC) studies to make a diagnosis. The goals of this prospective study were to assess the day-to-day practice in an academic setting, to determine how often these IHC tests were used on routine PNTBs, and to establish how often a combination of the BCC and P504S were helpful in diagnosing prostate cancer. A total of 772 prospectively collected PNB cases were examined over a 7-month period. IHC staining was performed in 171 cases (22%); 123 cases were stained with the BCC in addition to the commercially available monoclonal AMACR antibody. In 86 of these 123 cases (70%), both stains contributed to the final diagnosis: PCa in 44 cases, benign in 33 cases and high-grade prostatic intraepithelial neoplasia in 9 cases. Of the remaining 37 cases (30%), 18 were called benign or PCa, based solely on appropriate staining with the BCC, with AMACR being noncontributory because the focus of interest had been cut through (12 cases), there was negative staining with AMACR (in 4 PCa cases), or there was positive staining with AMACR (in 2 benign cases showing atrophy). Nineteen of 37 cases were diagnosed as atypical small acinar proliferation. In these 19 cases either the focus had been cut through on one or both of the stains (11 cases), both AMACR and BCC failed to work (2 cases), AMACR was positive in the presence of patchy BCC staining (1 cases), AMACR was negative in the absence of BCC staining (3 cases), or despite appropriate staining the focus consisted of 1 gland and was considered too small to call carcinoma (2 cases). Additional HIC stains were performed in 171 of 772 cases; of these, 123 had sufficient material to perform both the BCC and P504S. The BCC when used in combination with AMACR rendered a diagnosis in almost 70% of cases. Using these stains in combination may be a better approach in diagnostically difficult cases as it increases the likelihood that a definitive diagnosis can be rendered while decreasing the likelihood of an equivocal diagnosis. However, a limitation of this approach is the loss of tissue in these small lesions, suggesting that combining AMACR and the BCC on a single slide would be superior to using either marker separately. (C) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Dept Pathol Amory 3 195, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rubin, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol Amory 3 195, 75 Francis St, Boston, MA 02115 USA. OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [P50CA90381]; NIA NIH HHS [R01AG21404] NR 20 TC 54 Z9 59 U1 0 U2 2 PU W B SAUNDERS CO 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 DEC PY 2004 VL 35 IS 12 BP 1462 EP 1468 DI 10.1016/j.humpath.2004.09.009 PG 7 WC Pathology SC Pathology GA 882LR UT WOS:000225940900005 PM 15619204 ER PT J AU Lim, HK Lee, DC McKay, WB Protas, EJ Holmes, SA Priebe, MM Sherwood, A AF Lim, HK Lee, DC McKay, WB Protas, EJ Holmes, SA Priebe, MM Sherwood, A TI Analysis of sEMG during voluntary movement - Part II: Voluntary response index sensitivity SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE electromyography (EMG); motor control; spinal-cord injuries ID SPINAL-CORD INJURY; SURFACE EMG; GAIT AB In this paper, a method for analyzing surface electromyographic (sEMG) data recorded from the lower-limb muscles of incomplete spinal-cord injured (iSCI) subjects is evaluated. sEMG was recorded bilaterally from quadriceps, adductor, hamstring, tibialis anterior, and triceps surae muscles during voluntary ankle dorsillexion performed in the supine position as part of a comprehensive motor control assessment protocol. Analysis of the sEMG centered on two features, the magnitude of activation and the degree of similarity [similarity index (SI)] of the sEMG distribution to that of healthy subjects performing. the same maneuver (n = 10). The analysis calculations resulted in response vectors (RV) that were compared to healthy-subject-derived prototype response vectors resulting in a voluntary response index (VRI) [1]. Incomplete SCI subjects (n = 9) were used to test the sensitivity of this analysis method. They were given supported-weight treadmill ambulation training, which is expected to improve or at least not cause a deterioration of voluntary motor control. The VRI provided evidence that the quantitative sEMG analysis method used was able to differentiate between healthy subjects and those with iSCI, characterize individual differences among iSCI subjects, and track motor control changes occurring over time. C1 Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Med Ctr, Houston, TX 77030 USA. Methodist Rehabil Ctr, Jackson, MS 39216 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Edward Hines Jr Vet Affairs Hosp, Hines, IL 60141 USA. RP Lim, HK (reprint author), Baylor Coll Med, Houston, TX 77030 USA. OI Sherwood, Arthur/0000-0002-0110-4317 NR 22 TC 8 Z9 8 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD DEC PY 2004 VL 12 IS 4 BP 416 EP 421 DI 10.1109/TNSRE.2004.838445 PG 6 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 879UN UT WOS:000225744500006 PM 15614997 ER PT J AU Zhang, P Iwasaki-Arai, J Iwasaki, H Fenyus, ML Dayaram, T Owens, BM Shigematsu, H Levantini, E Huettner, CS Lekstrom-Himes, JA Akashi, K Tenen, DG AF Zhang, P Iwasaki-Arai, J Iwasaki, H Fenyus, ML Dayaram, T Owens, BM Shigematsu, H Levantini, E Huettner, CS Lekstrom-Himes, JA Akashi, K Tenen, DG TI Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBP alpha. SO IMMUNITY LA English DT Article ID BINDING-PROTEIN-ALPHA; COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; IN-VIVO; GRANULOCYTIC DIFFERENTIATION; LINEAGE COMMITMENT; DEFICIENT MICE; KNOCKOUT MICE; GENE; GRANULOPOIESIS AB The transcription factor C/EBPalpha is required for granulopoiesis and frequently disrupted in human acute myeloid leukemia (AML). Here, we show disruption of C/EBPalpha blocks the transition from the common myeloid to the granulocyte/monocyte progenitor but is not required beyond this stage for terminal granulocyte maturation. C/EBPalpha-deficient hematopoietic stem cells (HSCs) have increased expression of Bmi-1 and enhanced competitive repopulating activity. Bone marrow in adult C/EBPa-deficient mice was filled with myeloblasts, similar to human AML, supporting the notion that disruption of C/EBPalpha cooperates with other events in the development of leukemia. Therefore, C/EBPalpha is not only essential for granulocyte development but, in addition, is a regulator of hematopoietic stem cell activity. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Inst Med, Boston, MA 02115 USA. EM dtenen@bidmc.harvard.edu FU NCI NIH HHS [CA72009, CA78045]; NHLBI NIH HHS [HL56745] NR 42 TC 286 Z9 304 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2004 VL 21 IS 6 BP 853 EP 863 DI 10.1016/j.immuni.2004.11.006 PG 11 WC Immunology SC Immunology GA 881XB UT WOS:000225901600012 PM 15589173 ER PT J AU Lebedeva, T Anikeeva, N Kalams, SA Walker, BD Gaidarov, I Keen, JH Sykulev, Y AF Lebedeva, T Anikeeva, N Kalams, SA Walker, BD Gaidarov, I Keen, JH Sykulev, Y TI Major histocompatibility complex class I-intercellular adhesion molecule-1 association on the surface of target cells: implications for antigen presentation to cytotoxic T lymphocytes SO IMMUNOLOGY LA English DT Article DE antigen presentation; ICAM-1; membrane rafts; MHC class I; target cells ID HLA CLASS-I; MHC CLASS-I; SUPRAMOLECULAR ACTIVATION CLUSTERS; IMMUNOLOGICAL SYNAPSE FORMATION; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN LYMPHOBLASTOID-CELLS; ENDOTHELIAL-CELLS; PLASMA-MEMBRANE; TETRASPAN MICRODOMAINS; PEPTIDE COMPLEXES AB Polarization and segregation of the T-cell receptor (TCR) and integrins upon productive cytotoxic T-lymphocyte (CTL) target cell encounters are well documented. Much less is known about the redistribution of major histocompatibility complex class I (MHC-I) and intercellular adhesion molecule-1 (ICAM-1) proteins on target cells interacting with CTLs. Here we show that human leucocyte antigen-A2 (HLA-A2) MHC-I and ICAM-1 are physically associated and recovered from both the raft fraction and the fraction of soluble membranes of target cells. Conjugation of target cells with surrogate CTLs, i.e. polystyrene beads loaded with antibodies specific for HLA-A2 and ICAM-1, induced the accumulation of membrane rafts, and beads loaded with ICAM-1-specific antibodies caused the selective recruitment of HLA-A2 MHC-I at the contact area of the target cells. Disruption of raft integrity on target cells led to a release of HLA-A2 and ICAM-1 from the raft fraction, abatement of HLA-A2 polarization, and diminished the ability of target cells bearing viral peptides to induce a Ca2+ flux in virus-specific CTLs. These data suggest that productive engagement of ICAM-1 on target cells facilitates the polarization of MHC-I at the CTL-target cell interface, augmenting presentation of cognate peptide-MHC (pMHC) complexes to CTLs. We propose that ICAM-1-MHC-I association on the cell membrane is a mechanism that enhances the linkage between antigen recognition and early immunological synapse formation. C1 Thomas Jefferson Univ, BLSB 650, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sykulev, Y (reprint author), Thomas Jefferson Univ, BLSB 650, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. EM ysykulev@lac.jci.tju.edu FU NCI NIH HHS [5-T32-CA09683, T32 CA009683]; NIAID NIH HHS [5-T32-AI07523, AI39966, AI3254, R01 AI039966, T32 AI007523]; NIGMS NIH HHS [GM-28526, R01 GM028526] NR 54 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2004 VL 113 IS 4 BP 460 EP 471 DI 10.1111/j.1365-2567.2004.01985.x PG 12 WC Immunology SC Immunology GA 873FD UT WOS:000225264400006 PM 15554924 ER PT J AU Thrupp, L Bradley, S Smith, P Simor, A Gantz, N Crossley, K Loeb, M Strausbaugh, L Nicolle, L Bradley, S Crossley, K Gainer, RB Gantz, N Loeb, M Nicolle, L Quiros, R Simor, A Smith, P Steele, L Stevenson, K Strausbaugh, L Thrupp, L AF Thrupp, L Bradley, S Smith, P Simor, A Gantz, N Crossley, K Loeb, M Strausbaugh, L Nicolle, L Bradley, S Crossley, K Gainer, RB Gantz, N Loeb, M Nicolle, L Quiros, R Simor, A Smith, P Steele, L Stevenson, K Strausbaugh, L Thrupp, L CA SHEA Long-Term-Care Comm TI Tuberculosis prevention and control in long-term-care facilities for older adults SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Review ID MULTIDRUG-RESISTANT TUBERCULOSIS; BACTEC MGIT 960; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; SKIN-TEST; ISONIAZID CHEMOPROPHYLAXIS; MILIARY TUBERCULOSIS; CLINICAL SPECIMENS; DRUG-RESISTANCE; ELDERLY PERSONS AB In the United States, older adults comprise 22% of cases of tuberculous disease but only 12% of the population. Most cases of tuberculosis (TB) occur in community dwellers, but attack rates are highest among frail residents of long-term-care facilities. The detection and treatment of latent TB infection and TB disease can pose special challenges in older adults. Rapid recognition of possible disease, diagnosis, and implementation of airborne precautions are essential to prevent spread. It is the intent of this evidence-based guideline to assist healthcare providers in the prevention and control of TB, specifically in skilled nursing facilities for the elderly. C1 Univ Calif Irvine, Ctr Med, Infect Control Dept, Orange, CA 92868 USA. Univ Michigan, Dept Internal Med, Med Sch, Ann Arbor, MI 48109 USA. Univ Michigan, Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI 48109 USA. Univ Nebraska, Med Ctr, Dept Internal Med Infect Dis, Omaha, NE USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Microbiol, Toronto, ON, Canada. Boulder Community Hosp, Dept Infect Dis, Boulder, CO USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Minneapolis VA Med Ctr, Dept Educ, Minneapolis, MN USA. Minneapolis VA Med Ctr, Dept Internal Med, Minneapolis, MN USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. Hamilton Reg Lab Program, Hamilton, ON, Canada. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Hlth Sci Ctr, Dept Med, Winnipeg, MB, Canada. RP Thrupp, L (reprint author), Univ Calif Irvine, Ctr Med, Infect Control Dept, Bldg 53,Rm 220,101 City Dr, Orange, CA 92868 USA. NR 104 TC 20 Z9 20 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2004 VL 25 IS 12 BP 1097 EP 1108 DI 10.1086/502350 PG 12 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 879NS UT WOS:000225725100016 PM 15636299 ER PT J AU Shaffer, DW Gordon, JA Bennett, NL AF Shaffer, DW Gordon, JA Bennett, NL TI Learning, testing, and the evaluation of learning environments in medicine: Global performance assessment in medical education SO INTERACTIVE LEARNING ENVIRONMENTS LA English DT Article ID STRUCTURED CLINICAL EXAMINATION; GENERAL-PRACTITIONERS; STANDARDIZED PATIENTS; ORAL EXAMINATIONS; MANAGED CARE; COMPETENCE; RESIDENTS; OSCE; SKILLS; RELIABILITY AB Changes in the profession of medicine are creating the demand for a substantive reexamination of current practices in medical education. Many of the major issues in addressing this challenge are structural and political rather than scientific; here we address one critical scientific issue that will be important to (though not by itself adequate for) guiding such changes. The factor we address is the development of a global performance assessment: a standardized mechanism to assess individual skills and abilities that can be used to evaluate alternative educational interventions. We discuss the issues involved in developing such a system, and describe a set of principles for defining desired outcomes and developing assessment tools, including (a) wide clinical scope, (b) direct relationship to actual clinical performance, (c) reliability and repeatability, and (d) non-longitudinal measurement. We discuss the role of simulation, reflective practice, and portfolios of work in developing such a system, and argue that whatever form such metrics take, a system of global performance assessment will develop from close collaboration between clinicians and educators with innovative ways of thinking about performance and expertise. C1 Univ Wisconsin, Dept Educ Psychol, Madison, WI 53706 USA. Harvard Univ, Sch Med, Program Med Simulat, GS Beckwith Gilbert & Katharine S Gilbert Med Edu, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Continuing Educ, Cambridge, MA 02138 USA. RP Shaffer, DW (reprint author), Univ Wisconsin, Dept Educ Psychol, Educ Sci Room 1065,1025 W Johnson St, Madison, WI 53706 USA. EM dws@education.wisc.edu NR 52 TC 6 Z9 6 U1 0 U2 6 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1049-4820 J9 INTERACT LEARN ENVIR JI Interact. Learn. Environ. PD DEC PY 2004 VL 12 IS 3 BP 167 EP 178 DI 10.1080/10494820512331383409 PG 12 WC Education & Educational Research SC Education & Educational Research GA 890HS UT WOS:000226502900001 ER PT J AU Weingart, SN Toth, M Eneman, J Aronson, MD Sands, DZ Ship, AN Davis, RB Phillips, RS AF Weingart, SN Toth, M Eneman, J Aronson, MD Sands, DZ Ship, AN Davis, RB Phillips, RS TI Lessons from a patient partnership intervention to prevent adverse drug events SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE adverse drug event; medical error; patient participation ID SELF-MANAGEMENT; MEDICAL-CARE; QUALITY AB Background. Patient safety 'best practices' that call for patient participation to prevent adverse drug events have not been rigorously evaluated. Objective. To consider lessons learned from a patient partnership intervention to prevent adverse drug events among medical in-patients. Design. Prospective randomized, controlled pilot trial. Setting. Boston teaching hospital. Patients. Two hundred and nine adult in-patients on a general medicine unit. Intervention. Intervention patients (n = 107) received drug safety information and their medication list; controls (n = 102) received drug safety information only. Measurements. Adverse drug events and close-call drug errors were identified using chart review and incident reports from nurses, pharmacists, and physicians. Patients and clinicians were surveyed about the intervention. Results. In 1053 patient-days at risk, 11 patients experienced 12 adverse drug events and 16 patients experienced 18 close calls. There was a non-significant difference between intervention patients and controls in survey responses and in the adverse drug event rate (8.4% versus 2.9%, P = 0.12) and close-call rate (7.5% versus 9.8%, P = 0.57). Eleven percent of patients were aware of drug-related mistakes during the hospitalization. Among nurse respondents, 29% indicated that at least one medication error was prevented when a patient or family member identified a problem. Conclusion. Partnering with in-patients to prevent adverse drug events is a promising strategy but requires further study to document its efficacy. C1 Dana Farber Canc Inst, Ctr Patient Safey, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Stoneman Ctr Qual Improvement Gen Med & Primary C, Div Gen Med & Primary Care, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vermont, Coll Med, Burlington, VT USA. RP Weingart, SN (reprint author), Dana Farber Canc Inst, Ctr Patient Safey, 44 Binney St, Boston, MA 02115 USA. EM saul_weingart@dfci.harvard.edu FU AHRQ HHS [1 K08 HS 11644] NR 25 TC 29 Z9 31 U1 0 U2 3 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 DEC PY 2004 VL 16 IS 6 BP 499 EP 507 DI 10.1093/intqhc/mzh083 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 874PJ UT WOS:000225362000009 PM 15557360 ER PT J AU Dominguez, S Cooper, D Torriani, F Rodriguez-Torres, M Brau, N Sulkowski, W Sola, R Katlama, C Clumeck, N Nelson, MR Correa, MC Godofsky, EW Dieterich, D Duff, F Passe, S Lissen, E AF Dominguez, S Cooper, D Torriani, F Rodriguez-Torres, M Brau, N Sulkowski, W Sola, R Katlama, C Clumeck, N Nelson, MR Correa, MC Godofsky, EW Dieterich, D Duff, F Passe, S Lissen, E TI HCV-related factors but not HIV-related factors at baseline predict the response to treatment with peginterferon alfa-2a (40 kd) (pegasys) plus ribavirin (copegus) in patients with HIV-HCV co-infection: predictor analysis from the APRICOT study SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Meeting Abstract CT 6th European Congress of Chemotherapy and Infection/24th Interdisciphinary Meeting of Chimiotherapie Anit-Infections CY DEC 01-03, 2004 CL Paris, FRANCE C1 Univ New S Wales, Sydney, NSW, Australia. CHU St Pierre, Brussels, Belgium. HCFMUSP, Casa AIDS, Sao Paulo, Brazil. Hop La Pitie Salpetriere, Paris, France. Diego Res Fdn, Santurce, PR USA. Hosp del Mar, Barcelona, Spain. Virgen Rocio Univ Hosp, Seville, Spain. Chelsea & Westminster Hosp, London, England. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. Roche, Nutley, NJ USA. Univ Calif, San Diego, CA USA. Univ S Florida, Sch Med, Tampa, FL 33620 USA. RI mendes correa, maria cassia /A-6779-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD DEC PY 2004 VL 24 SU 2 BP S117 EP S117 PG 1 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 879RD UT WOS:000225734000127 ER PT J AU Gerson, S Mistry, R Bastani, R Blow, F Gould, R Llorente, M Maxwell, A Moye, J Olsen, E Rohrbaugh, R Rosansky, J Van Stone, W Jarvik, L AF Gerson, S Mistry, R Bastani, R Blow, F Gould, R Llorente, M Maxwell, A Moye, J Olsen, E Rohrbaugh, R Rosansky, J Van Stone, W Jarvik, L TI Symptoms of depression and anxiety (MHI) following acute medical/surgical hospitalization and post-discharge psychiatric diagnoses (DSM) in 839 geriatric US veterans SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Review DE depression; anxiety; MHI screening; medical/psychiatric comorbidities ID ILLNESS RATING-SCALE; ELDERLY MEDICAL INPATIENTS; PRIMARY-CARE PATIENTS; LATE-LIFE DEPRESSION; BIPOLAR-I DISORDER; GENERALIZED ANXIETY; MAJOR DEPRESSION; SUBTHRESHOLD DEPRESSION; OLDER-ADULTS; NONMAJOR DEPRESSION AB Objective We addressed the relatively unexplored use of screening scores measuring symptoms of depression and/or anxiety to aid in identifying patients at increased risk for post-discharge DSM-IV Axis I diagnoses. We were unable to find such studies in the literature. Method Elderly veterans without recent psychiatric diagnoses were screened for depression and anxiety symptoms upon admission to acute medical/surgical units using the Mental Health Inventory (MHI). Following discharge, those who had exceeded cut-off scores and had been randomized to UPBEAT Care (Unified Psychogeriatric Biopsychosocial Evaluation and Treatment, a clinical demonstration project) were evaluated for DSM diagnoses. We report on 839 patients, mostly male (96.3%; mean age 69.6 +/- 6.7 years), comparing three groups, i.e. those meeting screening criteria for symptoms of (i) depression only; (ii) anxiety only; and (iii) both depression and anxiety. Results Despite absence of recent psychiatric history, 58.6% of the 839 patients received a DSM diagnosis post-discharge (21.8% adjustment; 15.4% anxiety; 7.5% mood; and 14.0% other disorders). Patients meeting screening criteria for both depression and anxiety symptoms received a DSM diagnosis more frequently than those meeting criteria for anxiety symptoms only (61.9% vs 49.0%, p = 0.017), but did not differ significantly from those meeting criteria for depressive symptoms only (61.9% vs 56.8%, p = 0.174). Although exceeding the MHI screening cut-off scores for depression, anxiety, or both helped to identify patients with a post-discharge DSM diagnosis, the actual MHI screening scores failed to do so. Conclusion Screening hospitalized medical/surgical patients for symptoms of depression, anxiety, and particularly for the combination thereof, may help identify those with increased risk of subsequent DSM diagnoses, including adjustment disorder. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Stat Comp Ctr, Los Angeles, CA 90024 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. VAMC, Ann Arbor, MI USA. Miami VA Med Ctr, Miami, FL USA. Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33152 USA. VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Cent Off, Washington, DC USA. RP Jarvik, L (reprint author), 760 Westwood Blvd, Los Angeles, CA 90095 USA. EM ljarvik@ucla.edu RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 127 TC 7 Z9 7 U1 7 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD DEC PY 2004 VL 19 IS 12 BP 1155 EP 1167 DI 10.1002/gps.1217 PG 13 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 880QX UT WOS:000225805400005 PM 15526306 ER PT J AU Ferrando, AA Look, AT AF Ferrando, AA Look, AT TI DNA Microarrays in the diagnosis and management of acute lymphoblastic leukemia SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE DNA microarrays; classification of leukemias; prognosis evaluation; therapeutic targets ID GENE-EXPRESSION SIGNATURES; FLT3 MUTATIONS; MLL; CLASSIFICATION; PREDICTION; PROFILES; HEMATOPOIESIS; MECHANISMS; RESISTANCE; DISCOVERY AB The significant progress in the treatment of acute lymphoblastic leukemia (ALL) experienced over the last 3 decades has been driven mainly by the empirical combination of antileukemic drugs in highly intensive therapies. Further progress in the management of ALL is currently limited, however, by our incomplete understanding of the molecular pathways involved in leukemia pathogenesis and by the lack of useful prognostic markers for most patients. ne recent development of microarray technology, which allows the simultaneous analysis of gene expression levels for thousands of transcripts, has accelerated significantly the rate of progress in our understanding of the molecular basis of ALL. During the last few years, analysis of ALL samples with DNA arrays has facilitated the recognition of molecularly distinct leukemia groups, advanced our knowledge of the mechanisms of sensitivity and resistance to chemotherapy, generated novel prognostic prediction tools, and identified new targets for the development of molecularly tailored antileukemic agents. Thus, the introduction of microarray gene expression profiling has opened the opportunity for accelerated progress in the diagnosis and therapy of ALL, which will ultimately result in the development of novel highly effective and less toxic treatments for this disease. (C) 2004 The Japanese Society of Hematology. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ferrando, AA (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Mayer 630,44 Binney St, Boston, MA 02115 USA. EM adolfo-ferrando@dfci.harvard.edu RI Ferrando, Adolfo /Q-7026-2016 NR 32 TC 11 Z9 12 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD DEC PY 2004 VL 80 IS 5 BP 395 EP 400 DI 10.1532/IJH97.04137 PG 6 WC Hematology SC Hematology GA 884DO UT WOS:000226065000002 PM 15646649 ER PT J AU Jones, EL Zhao, MJ Stevenson, MA Calderwood, SK AF Jones, EL Zhao, MJ Stevenson, MA Calderwood, SK TI The 70kilodalton heat shock protein is an inhibitor of apoptosis in prostate cancer SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE HSP70; apoptosis; prostate; hyperthermia; quercetin ID IN-VITRO; TUMOR-CELLS; HSP70 GENES; QUERCETIN; EXPRESSION; RESISTANCE; INDUCTION; STRESS; HYPERTHERMIA; VIVO AB The 70kD heat shock protein (HSP70) plays essential cellular roles in mediating intracellular protein folding and protecting cells from proteotoxic stress. This study has examined the role of HSP70 in the expression of apoptosis in prostate carcinoma cells. Apoptosis was negatively correlated with HSP70 expression in PC-3 cells heat shocked in vivo. Further experiments carried out on an in vitro reconstituted system with isolated nuclei and cytoplasm from PC-3 cells showed that purified HSP70 directly inhibits apoptosis in a dose-dependant manner. Therefore, the potential role of depletion of intracellular HSP70 was examined as a means of inducing apoptosis in PC-3 cancer cells. Depletion of HSP70 by two independent strategies, either with anti-sense oligonucleotides directed against HSP70 mRNA or with the bioflavinoid drug quercetin, led to apoptosis in the absence of stress. In addition, quercetin pre-treatment synergistically enhanced apoptosis in combination with heat shock. Thus, HSP70 plays a physiological role in tumour cells as an inhibitor of apoptosis occurring both spontaneously and after stress and is a potential target for apoptosis-based cancer therapy. C1 Harvard Univ, Sch Med, BIDMC, Div Mol & Cellular Radiat Oncol, Boston, MA 02215 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, BIDMC, Div Mol & Cellular Radiat Oncol, Boston, MA 02215 USA. EM scalderw@bidmc.harvard.edu NR 28 TC 44 Z9 48 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD DEC PY 2004 VL 20 IS 8 BP 835 EP 849 DI 10.1080/02656730410001721807 PG 15 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 875WI UT WOS:000225452500003 PM 15764345 ER PT J AU Bianchi, J Fiorellini, JP Howell, TH Sekler, J Curtin, H Nevins, ML Friedland, B AF Bianchi, J Fiorellini, JP Howell, TH Sekler, J Curtin, H Nevins, ML Friedland, B TI Measuring the efficacy of rhBMP-2 to regenerate bone: A radiographic study using a commercially available software program SO INTERNATIONAL JOURNAL OF PERIODONTICS & RESTORATIVE DENTISTRY LA English DT Article ID MANDIBULAR RECONSTRUCTION; VOLUME; TOMOGRAPHY; PROTEIN-2; CT AB This radiographic study evaluated the efficacy of different concentrations of rhBMP-2 to regenerate bone in alveolar defects in the anterior maxilla. The study was performed using reasonably standardized CT examinations and the Simplant program. The radiographic measurements were further refined by careful standardization of the measured regions of interest. There was a statistically significant difference in bone formation between subjects treated with a concentration of 1.5 mg/mL rhBMP-2 compared with each of the other groups. There was no statistically significant difference in bone volume between any of the other groups. None of the groups showed a loss in bone volume. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02115 USA. RP Friedland, B (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM bernard_friedland@hsdm.harvard.edu NR 14 TC 19 Z9 21 U1 0 U2 0 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0198-7569 J9 INT J PERIODONT REST JI Int. J. Periodontics Restor. Dent. PD DEC PY 2004 VL 24 IS 6 BP 579 EP + PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 882LD UT WOS:000225939500008 PM 15626320 ER PT J AU Roach, M Winter, K Michalski, JM Cox, JD Purdy, JA Bosch, W Lin, X Shipley, WS AF Roach, M Winter, K Michalski, JM Cox, JD Purdy, JA Bosch, W Lin, X Shipley, WS TI Penile bulb dose and impotence after three-dimensional conformal radiotherapy for prostate cancer on RTOG 9406: Findings from a prospective, multi-institutional, phase I/II dose-escalation study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; three-dimensional conformal radiotherapy; impotence ID RADIATION-THERAPY; ERECTILE DYSFUNCTION; TOXICITY; LOCALIZATION; RISK; MEN; GY AB Purpose: To assess the relationship between the dose to the bulb of the penis and the risk of impotence in men treated on Radiation Therapy Oncology Group (RTOG) 9406. Methods and Materials: Men enrolled on a Phase I/II dose-escalation study, RTOG 9406, who were reported to be potent at entry and evaluable (n = 158) were selected for inclusion. Follow-up evaluations were scheduled every 3, 4, and 6 months for the first, second, and the third through fifth years, then annually. At each follow-up visit an assessment of potency status was made. Penile structures were defined by a single observer blinded to the potency status, using Web-based, on-line software. The dosimetry for penile structures was calculated at the Quality Assurance Center at Washington University and provided to RTOG Statistical Headquarters to determine whether there was a relationship between dose and impotence. Results: Patients whose median penile dose was greater than or equal to52.5 Gy had a greater risk of impotence compared with those receiving <52.5 Gy (p = 0.039). In a multivariate analysis neither age, the dose to the prostate, nor the use of hormonal therapy correlated with the risk of impotence. Conclusions: Dose to the bulb of the penis seems to be associated with the risk of radiation-induced impotence. (C) 2004 Elsevier Inc.= C1 Univ Calif San Francisco, Dept Radiat Oncol, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Washington Univ, Qual Assurance Ctr 3D, St Louis, MO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roach, M (reprint author), Univ Calif San Francisco, Dept Radiat Oncol, Ctr Comprehens Canc, 1600 Divisadero St,Suite H1031, San Francisco, CA 94143 USA. EM roach@radonc17.ucsf.edu FU NCI NIH HHS [U10CA215661, U10CA32115, U10CA37422] NR 26 TC 69 Z9 70 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2004 VL 60 IS 5 BP 1351 EP 1356 DI 10.1016/j.ijrobp.2004.05.026 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 877SX UT WOS:000225591600003 PM 15590164 ER PT J AU Zacks, DN Zheng, QD Han, Y Bakhru, R Miller, JW AF Zacks, DN Zheng, QD Han, Y Bakhru, R Miller, JW TI FAS-mediated apoptosis and its relation to intrinsic pathway activation in an experimental model of retinal detachment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; RAT MODEL; DEGENERATION; EXPRESSION; AIF AB PURPOSE. To determine whether the FAS-mediated apoptosis pathway becomes activated in the retina after retinal detachment and to investigate the temporal relationship between the activation of the FAS-pathway and the intrinsic apoptosis pathway involving caspase-9 and cytochrome c. METHODS. Experimental retinal detachments were created in Brown-Norway rats by injecting 10% hyaluronic acid into the subretinal space. Retinal tissue was harvested at 2, 4, 8, 24, 72, and 168 hours after creation of the detachment. Immunoprecipitation was performed to assess for FAS-receptor/FAS-ligand complex formation, and activation of caspase-8 and BID ( a member of the Bcl-2 family of proteins) was assessed by Western blot analysis. A caspase-9 activity assay and immunoprecipitation of the caspase-9/cytochrome c complex were performed at these same time points. Specific pathway inhibition was performed with the caspase-9 inhibitor zLEHD.fmk or neutralizing antibodies against either the FAS-receptor or FAS-ligand. Transcription levels of FAS and intrinsic pathway intermediates were assessed as a function of time after retinal detachment by using quantitative real-time polymerase chain reaction. RESULTS. Retinal detachment resulted in the time-dependent formation of the FAS-receptor/FAS-ligand complex that preceded the peak of caspase-9 activity and caspase-9/cytochrome c complex formation. Cleavage of caspase-8 and truncation of BID were also observed. Injection of zLEHD.fmk into the subretinal space of a detached retina resulted in decreased caspase-9 activity, as did injection of anti-FAS-receptor antibody into either the subretinal space or the vitreous. Retinal detachment resulted in the transcriptional upregulation of the FAS-receptor, FAS-ligand, caspase-8 and BID, but not caspase-9 and cytochrome c. CONCLUSIONS. The FAS-mediated apoptosis pathway becomes activated and transcriptionally upregulated after retinal detachment. The peak of FAS activation precedes that of the intrinsic pathway, and inhibition of FAS activation can decrease caspase-9 activity. C1 Univ Michigan, Sch Med, Kellogg Eye Ctr, Retina Serv,Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48105 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Zacks, DN (reprint author), Univ Michigan, Sch Med, Kellogg Eye Ctr, Retina Serv,Dept Ophthalmol & Visual Sci, 1000 Wall St, Ann Arbor, MI 48105 USA. EM davzacks@umich.edu RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 FU NEI NIH HHS [K08-EY14705-01] NR 16 TC 48 Z9 53 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2004 VL 45 IS 12 BP 4563 EP 4569 DI 10.1167/iovs.04-0598 PG 7 WC Ophthalmology SC Ophthalmology GA 873GZ UT WOS:000225269200044 PM 15557468 ER PT J AU Lembcke, A Borges, AC Dohmen, PM Hoffmann, U Hermann, KGA Kroencke, TJ Fischer, T Hamm, B Enzweiler, CNH AF Lembcke, A Borges, AC Dohmen, PM Hoffmann, U Hermann, KGA Kroencke, TJ Fischer, T Hamm, B Enzweiler, CNH TI Quantification of functional mitral valve regurgitation in patients with congestive heart failure: Comparison of electron-beam computed tomography with cardiac catheterization SO INVESTIGATIVE RADIOLOGY LA English DT Article DE computed tomography (CT); electron beam; catheters and catheterization; echocardiography; heart; mitral valve; regurgitation ID LEFT-VENTRICULAR VOLUME; FLOW MEASUREMENTS; DOPPLER-ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; CORONARY-ANGIOGRAPHY; EJECTION FRACTION; IMAGE QUALITY; OUTPUT; THERMODILUTION; VALIDATION AB Objectives: We sought to determine the agreement between electron-beam computed tomography (CT) and cardiac catheterization for the quantification of mitral regurgitation and to evaluate their association with echocardiographic assessment. Material and Methods: Fifty patients with congestive heart failure were examined both by electron-beam CT and catheterization to calculate mitral regurgitation volume and fraction based on the difference between the left ventricular stroke and aortic flow volume. The severity of regurgitation was also compared with visual assessment by echocardiography (grade, 0-4+). Results: The mean values for the mitral regurgitation volume and fraction did not differ significantly between electron-beam CT and catheterization (mean differences: 0.2 mL/m(2) and -0.9%, P > 0.05 each, limits of agreement: -14.0 to 14.4 mL/m(2) and -26.3 to 24.5%, respectively) and showed a good correlation (r = 0.79 and r = 0.76, respectively; P < 0.05 each). Good levels of correlation were observed between echocardiographic severity grading and quantitative measurements of regurgitation volume and fraction, which were somewhat better between echocardiography and electron-beam CT (r(S) = 0.78 and r(S) = 0.84, respectively; P < 0.05 each) than between echocardiography and catheterization (r(S) = 0.72 and r(S) = 0.81, respectively; P < 0.05 each). Conclusion: Our results suggest that electron-beam CT allows for quantification of mitral valve regurgitation with similar accuracy as cardiac catheterization. Measurements with both modalities correlated well with the results of echocardiographic assessment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Med Berlin, Charite Med Sch, Dept Radiol, Berlin, Germany. Univ Med Berlin, Charite Med Sch, Dept Internal Med 1, Cardiol Angiol & Pulm Sect, Berlin, Germany. Univ Med Berlin, Charite Med Sch, Dept Cardiovasc Surg, Berlin, Germany. RP Lembcke, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White Bldg 270, Boston, MA 02114 USA. EM alexander.lembcke@gmx.de RI Kroencke, Thomas/H-6423-2011 NR 47 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 2004 VL 39 IS 12 BP 728 EP 739 DI 10.1097/00004424-200412000-00004 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 874BT UT WOS:000225326600004 PM 15550834 ER PT J AU Magen, E Viskoper, R Mishal, J Priluk, R Berezovsky, A Laszt, A London, D Yosefy, C AF Magen, E Viskoper, R Mishal, J Priluk, R Berezovsky, A Laszt, A London, D Yosefy, C TI Resistant arterial hypertension and hyperlipidemia: Atorvastatin, not vitamin C, for blood pressure control SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE resistant hypertension; statins; vitamin C; endothelial function ID REFRACTORY HYPERTENSION; ENDOTHELIAL FUNCTION; ASCORBIC-ACID; HYPERCHOLESTEROLEMIA; INFLAMMATION; STRESS AB Background: Hypertension is considered resistant if blood pressure cannot be reduced to < 140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP goals. Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia. Methods: Forty-eight hyperlipidemic subjects with RH (office systolic BP >140 mmHg and/or office diastolic BP >90 mmHg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) - mean 24 hour SBP 150.6 +/- 5.2 mmHg, DBP 86.1 +/- 3.3 mmHg, low density lipoprotein 158.1 +/- 24.5 mg/dl - received vitamin C 500 mg per day; Group ATR (n = 15) - mean 24 hour SBP 153.1 +/- 4.8 mmHg, DBP 87.1 +/- 6.7 mmHg, LDL 162.6 +/- 13.6 mg/dl - received atorvastatin 20 mg/day; and Group PLA (n = 16) - mean 24 hour SBP 151.1 +/- 7.4 mmHg, DBP 84.8 +/- 5.9 mmHg, LDL 156.7 +/- 26.1 mg/dl - received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks. Results: In the ATR group there were significant reductions of SBP (DeltaSBP1-2:13.7 +/- 5.6 mmHg, P 0.001), DBP (DeltaDBP1-2:7.8 +/- 5.7 mmHg, P 0.01), LDL (DeltaLDL1-2: 67.7 +/- 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD (DeltaFMD2-1: 4.2 +/- 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups. Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods. C1 Barzilai Govt Hosp, WHO, Collaborat Ctr Prevent CVD, IL-78306 Ashqelon, Israel. Barzilai Govt Hosp, Dept Radiol, IL-78306 Ashqelon, Israel. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. RP Magen, E (reprint author), Barzilai Govt Hosp, WHO, Collaborat Ctr Prevent CVD, IL-78306 Ashqelon, Israel. EM elimgen2@netvision.net.il RI Magen, Eli/N-7960-2014 OI Magen, Eli/0000-0002-7713-423X NR 24 TC 30 Z9 32 U1 0 U2 0 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISRAEL MED ASSOC J JI Isr. Med. Assoc. J. PD DEC PY 2004 VL 6 IS 12 BP 742 EP 746 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 878RA UT WOS:000225663100005 PM 15609886 ER PT J AU Francois-Bongarcon, V Feng, Y Lee, SK Chen, G Shankar, P Liu, Y Tao, X Shao, YM Lieberman, J AF Francois-Bongarcon, V Feng, Y Lee, SK Chen, G Shankar, P Liu, Y Tao, X Shao, YM Lieberman, J TI Cross-clade CD8 T-cell responses to HIVIIIB and Chinese B ' and C/B ' viruses in North American and Chinese HIV-seropositive donors SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; vaccine; CD8 T lymphocyte; cytolysis; IFN-gamma; cross-clade ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; LYMPHOCYTE RESPONSES; IMMUNE-RESPONSES; TYPE-1 GENOME; RECOGNITION; EPITOPE; REACTIVITY; VACCINE; NEUTRALIZATION AB HIV variation presents an obstacle to a global AIDS vaccine. Viral diversity and host variations in MHC expression both affect vaccine responses. Whether CD8 T cells from HIV-infected donors in 1 part of the world cross-recognize isolates from other regions will provide guidance about whether country-specific vaccines are needed. We compared recognition of HIVIIIB and representative B' (Thai B) and recombinant C/B' virus strains endemic in China by CD8 T cells from 7 HIV-infected North American donors and 4 Chinese donors. IFN-gamma production in response to HIV,,,, or the Chinese viruses was comparable. Although 1.6 +/- 0.8% of American donor CD8 T cells produced IFN-gamma above the background level in response to IIIB virus, 1.5 +/- 0.8% responded to B' virus, and 1.4 +/- 0.7% responded to C/B' vir-us. Responses to adherent cells infected with vaccinia viruses expressing B' and C/B' virus gag and env were also comparable in magnitude with responses to IIIB virus. Cytolysis of CD4 T cells infected with B' virus was comparable with lysis of cells infected with IIIB virus, but lysis of the more divergent C/B' virus was somewhat reduced. T cells, selected for IFN-gamma production to IIIB virus, also efficiently lysed cells infected with Chinese viruses. Therefore, cross-clade CD8 T-cell responses to IIIB virus and prevalent Chinese viral strains are common. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Chinese Acad Prevent Med, Natl Ctr AIDS Prevent & Control, Beijing, Peoples R China. RP Lieberman, J (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM lieberman@cbr.med.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [U19 AI51915] NR 66 TC 5 Z9 5 U1 0 U2 0 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 DEC 1 PY 2004 VL 37 IS 4 BP 1435 EP 1444 DI 10.1097/01.qai.0000145220.81304.b0 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 876FL UT WOS:000225481800001 PM 15602120 ER PT J AU Shera, CA Tubis, A Talmadge, CL AF Shera, CA Tubis, A Talmadge, CL TI Do forward- and backward-traveling waves occur within the cochlea? Countering the critique of Nobili et al. SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE inner ear; middle ear; otoacoustic emissions; cochlear mechanics ID OTOACOUSTIC EMISSIONS; BASILAR-MEMBRANE; IMPEDANCE; MODEL; EAR AB The question of whether or not forward- and backward-traveling waves occur within the cochlea constitutes a long-standing controversy in cochlear mechanics recently brought to the fore by the problem of understanding otoacoustic emissions. Nobili and colleagues articulate the opposition to the traveling-wave viewpoint by arguing that wave-equation formulations of cochlear mechanics fundamentally misrepresent the hydrodynamics of the cochlea [e.g., Nobili et al. (2003) J. Assoc. Res. Otolaryngol. 4:478-494]. To correct the perceived deficiencies of the wave-equation formulation, Nobili et al. advocate an apparently altogether different approach to cochlear modeling-the so-called "hydrodynamic" or "Green's function" approach-in which cochlear responses are represented not as forward- and backward-traveling waves but as weighted sums of the motions of individual basilar membrane oscillators, each interacting with the others via forces communicated instantaneously through the cochlear fluids. In this article, we examine Nobili and colleagues' arguments and conclusions while attempting to clarify the broader issues at stake. We demonstrate that the one-dimensional wave-equation formulation of cochlear hydrodynamics does not misrepresent long-range fluid coupling in the cochlea, as claimed. Indeed, we show that the long-range component of Nobili et al.'s three-dimensional force propagator is identical to the hydrodynamic Green's function representing a one-dimensional tapered transmission line. Furthermore, simulations that Nobili et al. use to discredit wave-equation formulations of cochlear mechanics (i.e., cochlear responses to excitation at a point along the basilar membrane) are readily reproduced and interpreted using a simple superposition of forward- and backward-traveling waves. Nobili and coworkers' critique of wave-equation formulations of cochlear mechanics thus appears to be without compelling foundation. Although the traveling-wave and hydrodynamic formulations impose strikingly disparate conceptual and computational frameworks, the two approaches ultimately describe the same underlying physics. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02115 USA. Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA. Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R29 DC03094, R01 DC03687, R01 DC003687] NR 38 TC 12 Z9 14 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2004 VL 5 IS 4 BP 349 EP 359 DI 10.1007/s10162-004-4038-1 PG 11 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 871VJ UT WOS:000225164400002 PM 15675000 ER PT J AU Meisenhelder, JB Marcum, JP AF Meisenhelder, JB Marcum, JP TI Responses of clergy to 9/11: Posttraumatic stress, coping, and religious outcomes SO JOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION LA English DT Article ID LIFE EVENTS; PTSD; DISORDER; INTRUSION; AROUSAL AB This study examines posttraumatic stress, religious coping, and nonreligious coping in relation to positive religious outcomes following the tragedies of 9/11. In November 2001, a mailed survey of 814 active, ordained ministers in the Presbyterian Church (U.S.A.) measured posttraumatic stress, perceived threat, coping activities, positive and negative religious coping, positive religious outcomes, and perceived congregational responses. A majority of the respondents (75 percent) experienced some posttraumatic stress symptoms, with 63 percent feeling threatened for their personal safety. Nonreligious coping behaviors included contributing money (60 percent) and displaying the flag (56 percent). Looking to God for strength, support, and guidance was the most frequently used strategy; increased prayer was second. High stress was associated with higher frequency of coping strategies, both religious and nonreligious. More frequent positive religious coping was related to less severe stress symptoms of numbness and avoidance, and higher positive religious outcomes. Although religion failed to provide protection against stress in a population of religiously dedicated individuals, it provided a pathway for positive and effective coping strategies that resulted in positive religious outcomes. C1 Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02129 USA. Presbyterian Church USA, Res Serv, Louisville, KY USA. RP Meisenhelder, JB (reprint author), Massachusetts Gen Hosp, MGH Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA. EM Meisenhelder.Janice@mgh.harvard.edu; jmarcum@ctr.pcusa.org NR 22 TC 19 Z9 20 U1 1 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0021-8294 J9 J SCI STUD RELIG JI J. Sci. Stud. Relig. PD DEC PY 2004 VL 43 IS 4 BP 547 EP 554 DI 10.1111/j.1468-5906.2004.00255.x PG 8 WC Sociology; Religion SC Sociology; Religion GA 875IK UT WOS:000225413500007 ER PT J AU Yerevanian, BI Feusner, JD Koek, RJ Mintz, J AF Yerevanian, BI Feusner, JD Koek, RJ Mintz, J TI The dexamethasone suppression test as a predictor of suicidal behavior in unipolar depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE dexamethasone; depressive disorder; dysthymic disorder; suicide; attempted; suicide ID CEREBROSPINAL-FLUID; AMINE METABOLITES; METAANALYSIS; DISORDERS AB Background: Non-suppression on the dexamethasone suppression test (DST) in unipolar depression has been found to be associated with completed suicide, with less consistent data for attempted suicide and hospitalizations for suicidality. The purpose of this study was to examine DST non-suppression as a predictor of these three aspects of suicidal behaviour. Methods: Records were reviewed for 101 patients who met criteria for major depressive disorder and/or dysthymic disorder and had a DST performed. All patients were treated naturalistically and were followed for an average of 2 years. DST suppressors and non-suppressors were compared with respect to three outcomes: (1) completed suicide; (2) attempted suicide; and (3) hospitalizations for suicidality. Results: DST non-suppressors were significantly more likely to have completed suicide or be hospitalized for suicidality than DST suppressors, with a non-significant trend for attempts. Total suicidal events were also significantly more frequent in the non-suppressor group. Limitations: Axis II diagnoses and,severity of illness were not assessed. Knowledge of DST results may have influenced the decision to hospitalize patients. Conclusions: DST non-suppression identifies unipolar depressed patients with a higher risk for future suicide completion or hospitalization for suicidality. Performance of DST upon initiation of treatment may be a useful adjunct in identifying suicidal risk. Published by Elsevier B.V. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Biostat Consultat Unit, Los Angeles, CA 90073 USA. RP Yerevanian, BI (reprint author), 16111 Plummer St,116A-11, North Hills, CA 91343 USA. EM byerevan@ucla.edu RI Feusner, Jamie/K-2312-2012 OI Feusner, Jamie/0000-0002-0391-345X NR 32 TC 50 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2004 VL 83 IS 2-3 BP 103 EP 108 DI 10.1016/j.jad.2004.08.009 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 880XA UT WOS:000225822100001 PM 15555702 ER PT J AU Bauer, M Fairbanks, L Berghofer, A Hierholzer, J Bschor, T Baethge, C Rasgon, N Sasse, J Whybrow, PC AF Bauer, M Fairbanks, L Berghofer, A Hierholzer, J Bschor, T Baethge, C Rasgon, N Sasse, J Whybrow, PC TI Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE L-thyroxine; supraphysiological doses; affective disorders; bone mineral density; dual energy x-ray absorptiometry; DXA ID BIPOLAR AFFECTIVE-DISORDER; L-THYROXINE TREATMENT; SUBCLINICAL HYPERTHYROIDISM; REFRACTORY DEPRESSION; POSTMENOPAUSAL WOMEN; SKELETAL INTEGRITY; THYROID-HORMONES; METAANALYSIS; MASS; PREMENOPAUSAL AB Background: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T-4), show evidence of accelerated bone loss compared to the reference population database. Methods: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter. and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T-4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T-4 (mean dose=416 mcg/d) therapy. Results: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T-4, with higher doses being positively correlated with the percentage decline of BNID. Limitations: Relatively small sample size, no bone density assessment prior to treatment with L-T-4, no patient control group with mood disorders who did not receive L-T-4 treatment, and bone density follow-up intervals were variable. Conclusions: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T-4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed. (C) 2004 Elsevier B.V. All rights reserved. C1 Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Neuropsychiat Inst & Hosp, Los Angeles, CA USA. Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. Charite Univ Med Berlin, Dept Radiol & Nucl Med, Berlin, Germany. Tech Univ Dresden, Dept Psychiat, Dresden, Germany. Harvard Univ, McLean Hosp, Sch Med,Bipolar & Psychot Disorders Program, Consolidated Dept Psychiat,Massachusetts Gen Hosp, Belmont, MA 02178 USA. Stanford Univ, Sch Med, Dept Psychiat, Palo Alto, CA 94304 USA. RP Bauer, M (reprint author), Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Campus Charite Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. EM michael.bauer@charite.de NR 26 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2004 VL 83 IS 2-3 BP 183 EP 190 DI 10.1016/j.jad.2004.08.011 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 880XA UT WOS:000225822100011 PM 15555712 ER PT J AU Yan, LJ Hammen, C Cohen, AN Daley, SE Henry, RM AF Yan, LJ Hammen, C Cohen, AN Daley, SE Henry, RM TI Expressed emotion versus relationship quality variables in the prediction of recurrence in bipolar patients SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; social support; recurrence; expressed emotion; perceived criticism; polarity-specificity ID SOCIAL SUPPORT; PSYCHIATRIC-PATIENTS; PERCEIVED CRITICISM; DISORDER; RELAPSE; DEPRESSION; MANIA AB Background: The expressed emotion (EE) construct has predicted clinical outcomes in schizophrenia and depression, but few studies have been conducted with bipolar patients. Moreover, there is a particular dearth of information regarding the prediction of depressive versus manic episodes in bipolar patients. Questions also remain about the utility of EE compared to other variables (perceived criticism, relationship negativity, and chronic strain in close relationships) that more directly evaluate interpersonal stress and about specific predictions of mania or depression. Methods: Forty-seven outpatients with bipolar I disorder participated in a 1-year longitudinal study. A close collateral of the patient completed the Five Minute Speech Sample (FMSS) to assess EE, and participants completed perceived criticism and negativity ratings of collaterals. Clinical outcomes and chronic interpersonal stress were assessed by interview at 3-month intervals. Results: High EE predicted depressive, but not manic recurrence. Other variables of close interpersonal relationships were not significant predictors of recurrence. Limitations: Participants nominated collaterals, and those who did not have such a confidant were excluded. Conclusions: The FMSS was sensitive to even mild negativity by the collateral that predicted later depressive episodes. This is the first study to demonstrate polarity-specific effects of EE on the prediction of recurrence in bipolar disorder. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. W Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. MIRECC, Los Angeles, CA USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Yan, LJ (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,POB 951563,405 Hilgard Ave, Los Angeles, CA 90095 USA. EM ljyan@ucla.edu NR 25 TC 62 Z9 63 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2004 VL 83 IS 2-3 BP 199 EP 206 DI 10.1016/j.jad.2004.08.006 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 880XA UT WOS:000225822100013 PM 15555714 ER PT J AU Biederman, J Kwon, A Wozniak, J Mick, E Markowitz, S Fazio, V Faraone, SV AF Biederman, J Kwon, A Wozniak, J Mick, E Markowitz, S Fazio, V Faraone, SV TI Absence of gender differences in pediatric bipolar disorder: findings from a large sample of referred youth SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE pediatric; bipolar disorder; gender ID DEFICIT HYPERACTIVITY DISORDER; CLINICAL-PICTURE; MIXED MANIA; CHILDREN; ADOLESCENTS; DIAGNOSIS; SUBTYPE; WOMEN AB Background: Because little is known about gender differences in pediatric bipolar disorder, we evaluated whether gender moderates the expression of pediatric bipolar disorder in a large clinical sample. Methods: Subjects were consecutively referred youth aged 18 years or less who met full criteria for DSM-III-R bipolar disorder (BPD) (females, n=74; BD males, n=224). All subjects were assessed with a structured diagnostic interview and measures of psychosocial and family functioning. Results: Most of the bipolar subjects (91% of males, 70% of females) also had ADHD. Bipolar disorder was equally prevalent in both genders. Among females and males, severe irritability (83% and 80%, respectively), mixed presentation (87% and 84%, respectively), chronic course (84% and 77%, respectively) and prepubertal onset (78% and 93%, respectively) predominated the clinical picture. We found no meaningful differences between genders in the number of BPD symptoms, type of treatment for BPD (counseling, medication, hospitalization), severity of educational deficits, severity of family and interpersonal functioning or patterns of psychiatric comorbidity. Conclusions: Because gender does not moderate the clinical expression of pediatric bipolar disorder, our data does not suggest that gender specific criteria for the disorder are warranted. (C) 2004 Elsevier B.V All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, Clin & Res Program Pediat Psychopharmacol, WACC 725,15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 28 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 2004 VL 83 IS 2-3 BP 207 EP 214 DI 10.1016/j.jad.2004.08.005 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 880XA UT WOS:000225822100014 PM 15555715 ER PT J AU Faes, C Geys, H Aerts, M Molenberghs, G Catalano, PJ AF Faes, C Geys, H Aerts, M Molenberghs, G Catalano, PJ TI Modeling combined continuous and ordinal outcomes in a clustered setting SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE benchmark dosed; clustering; Plackett-Dale model; pseudo-likelihood; quantitative risk assessment ID LATENT VARIABLE MODELS; DEVELOPMENTAL TOXICOLOGY; RISK ASSESSMENT; REGRESSION-MODELS; MIXED DISCRETE; FETAL WEIGHT; BIVARIATE; BINARY; TOXICITY; RESPONSES AB Measurements of both continuous and categorical outcomes appear in many statistical problems. One such example is the study of teratology and developmental toxicity, where both the probability that a live fetus is malformed (ordinal) or of low birth weight (continuous) are important measures in the context of teratogenicity. Although multivariate methods of the analysis of continuous outcomes are well understood. methods for jointly continuous and discrete outcomes are less familiar. We propose a likelihood-based method that is an extension of the Plackett-Dale approach. Specification of the full likelihood will be avoided using pseudo-likelihood methodology. The estimation of safe dose levels as part of quantitative risk assessment will be illustrated based on a developmental toxicity experiment of diethylene glycol dimethyl ether in mice. C1 Limburgs Univ Ctr, Ctr Stat, Diepenbeek, Belgium. Harvard Univ, Sch Publ Hlth, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Faes, C (reprint author), Limburgs Univ Ctr, Ctr Stat, Univ Campus, Diepenbeek, Belgium. EM christel.faes@luc.ac.be RI Faes, Christel/E-1384-2017 OI Faes, Christel/0000-0002-1878-9869 NR 44 TC 6 Z9 6 U1 1 U2 4 PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGR BIOL ENVIR ST JI J. Agric. Biol. Environ. Stat. PD DEC PY 2004 VL 9 IS 4 BP 515 EP 530 DI 10.1198/108571104X16349 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 882BI UT WOS:000225913100007 ER PT J AU Miklossy, J Khalili, K Gern, L Ericson, RL Darekar, P Bolle, L Hurlimann, J Paster, BJ AF Miklossy, J Khalili, K Gern, L Ericson, RL Darekar, P Bolle, L Hurlimann, J Paster, BJ TI Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; amyloid; bacteria; Borrelia burgdorferi; chronic inflammation; lyme disease; spirochetes; syphilis ID SIMPLEX-VIRUS TYPE-1; TREPONEMA-PALLIDUM; CHLAMYDIA-PNEUMONIAE; DIAGNOSIS; SPIROCHETOSIS; INVOLVEMENT; CULTURE; FIBER; MICE AB The cause, or causes, of the vast majority of Alzheimer's disease cases are unknown. A number of contributing factors have been postulated, including infection. It has long been known that the spirochete Teponema pallidum, which is the infective agent for syphilis, can in its late stages cause dementia, chronic inflammation, cortical atrophy and amyloid deposition. Spirochetes of unidentified types and strains have previously been observed in the blood, CSF and brain of 14 AD patients tested and absent in 13 controls. In three of these AD cases spirochetes were grown in a medium selective for Borrelia burgdorferi. In the present study, the phylogenetic analysis of these spirochetes was made. Positive identification of the agent as Borrelia burgdorferi sensu stricto was based on genetic and molecular analyses. Borrelia antigens and genes were co-localized with beta-amyloid deposits in these AD cases. The data indicate that Borrelia burgdorferi may persist in the brain and be associated with amyloid plaques in AD. They suggest that these spirochetes, perhaps in an analogous fashion to Treponema pallidum, may contribute to dementia, cortical atrophy and amyloid deposition. Further in vitro and in vivo studies may bring more insight into the potential role of spirochetes in AD. C1 Univ British Columbia, Dept Psychiat, Kinsmen Lab Neurol Res, Vancouver, BC V6T 1Z3, Canada. Univ Lausanne, Sch Med, CHUV, Inst Pathol,Div Neuropathol, CH-1011 Lausanne, Switzerland. Temple Univ, Coll Sci & Technol, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. Univ Neuchatel, Inst Zool, CH-2007 Neuchatel, Switzerland. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. CHU Vaudois, Univ Med Sch, Ctr Blood Transfus, CH-1011 Lausanne, Switzerland. RP Miklossy, J (reprint author), Univ British Columbia, Dept Psychiat, Kinsmen Lab Neurol Res, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. EM judmik@telus.net NR 48 TC 42 Z9 42 U1 2 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD DEC PY 2004 VL 6 IS 6 BP 639 EP 649 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 897QW UT WOS:000227020700008 PM 15665404 ER PT J AU Bartzokis, G Lu, PH Mintz, J AF Bartzokis, G Lu, PH Mintz, J TI Quantifying age-related myelin breakdown with MRI: Novel therapeutic targets for preventing cognitive decline and Alzheimer's disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE myelin; oligodendrocyte; white matter; degeneration; dementia; development; aging; Alzheimer's disease; amyloid; beta; tau; MRI; relaxation rate; cholesterol; iron; metal; chelation; nicotine; MCI; AAMI; cognitive; memory; impairment; medications; treatment; brain; neurons ID WHITE-MATTER; NERVE-FIBERS; BRAIN; VOLUMES; MONKEY; MODEL; RAT AB Myelin plays an essential role in brain structure and function and the human brain is uniquely dependent on the elaboration of this late invention of evolution. Our brain has the most extensive and protracted process of myelination that extends to approximately age 50 in cortical regions that have the highest risk for developing Alzheimer's disease (AD) pathology. This myelin-centered model of the human brain asserts that unique vulnerabilities of myelin, especially late-developed myelin, and the oligodendrocytes that produce it are directly pertinent to many uniquely human neuropsychiatric diseases including late-life neurodegenerative disorders such as AD. Magnetic resonance imaging (MRI) technology permits the in vivo assessment of the roughly quadratic (inverted U) lifelong trajectory of human myelin development and its subsequent breakdown. There is close agreement between neuropsychology, neuropathology, and imaging measures suggesting that the process of myelin breakdown begins in adulthood, accelerates as aging progresses, and underlies both age-related cognitive declines and the most powerful risk factor of dementia-causing disorders such as AD: age. This myelin-centered model together with the technology that makes it possible to measure the trajectory of myelin breakdown provide a framework for developing novel treatments, as well as assessing efficacy of currently available treatments, intended to slow or reverse the breakdown process in both clinically healthy as well as symptomatic populations. Such treatments can be expected to have a wide spectrum of efficacy and impact multiple human disease processes including potentially slowing brain aging and thus provide opportunities for primary prevention of age-related degenerative disorders such as AD. C1 Univ Calif Los Angeles, Alzheimers Dis Ctr, David Gheffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Gheffen Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Charles R Drew Univ Med & Sci, Dept Psychiat, Los Angeles, CA 90043 USA. Univ Calif Los Angeles, David Gheffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Alzheimers Dis Ctr, David Gheffen Sch Med, Dept Neurol, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. EM gbar@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG16570]; NIMH NIH HHS [MH0266029] NR 19 TC 41 Z9 42 U1 0 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD DEC PY 2004 VL 6 IS 6 SU S BP S53 EP S59 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 900JT UT WOS:000227211900010 PM 15665415 ER PT J AU Longo, FM Massa, SM AF Longo, FM Massa, SM TI Neurotrophin-based strategies for neuroprotection SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article ID NERVE GROWTH-FACTOR; AMYLOID-BETA-PEPTIDE; INDUCED NEURONAL APOPTOSIS; SMALL-MOLECULE MIMETICS; ALZHEIMERS-DISEASE; CORTICAL-NEURONS; GENE-THERAPY; CELL-DEATH; RECEPTOR; P75 AB Neurotrophins activate a number of signaling pathways relevant to neuroprotection; however, their poor pharmacological properties and their pleiotropic effects resulting from interaction with the p75(NTR)-Trk-sortilin three-receptor signaling system limit therapeutic application. While local application of neurotrophin proteins addresses some of the pharmacological challenges, selective targeting of neurotrophin receptors might allow for more selective application of neurotrophin receptor signaling modulation. Recent studies have supported the feasibility of developing non-peptidyl small molecules that mimic specific domains of neurotrophins and modulate signaling of specific neurotrophin receptors. The expression of p75(NTR) by populations of neurons most vulnerable in Alzheimer's disease and the linkage of p75(NTR) signaling to aberrant signaling mechanisms occurring in this disorder, point to potential applications for p75(NTR)-based small molecule strategies. Small molecules targeted to p75(NTR) in the settings of neurodegenerative disease and other forms of neural injury might serve to inhibit death signaling, block proNGF-mediated degenerative signaling and minimize deleterious effects promoted by pharmacologically upregulated Trk signaling. C1 Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Longo, FM (reprint author), Univ N Carolina, Sch Med, Dept Neurol, CB7025, Chapel Hill, NC 27599 USA. EM longof@glial.med.unc.edu FU NIA NIH HHS [R01 AG09873] NR 47 TC 17 Z9 17 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD DEC PY 2004 VL 6 IS 6 SU S BP S13 EP S17 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 900JT UT WOS:000227211900004 PM 15665408 ER PT J AU Huang, XD Atwood, CS Moir, RD Hartshorn, MA Tanzi, RE Bush, AI AF Huang, XD Atwood, CS Moir, RD Hartshorn, MA Tanzi, RE Bush, AI TI Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's A beta peptides SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE A beta amyloid; A beta oligomerization; Alzheimer's disease; metal chelator; trace metal contaminants ID TRANSGENIC MICE; SENILE PLAQUES; CELL-CULTURE; IN-VIVO; DISEASE; PROTEIN; ZINC; AGGREGATION; COPPER; BRAIN AB Nucleation-dependent protein aggregation ("seeding'') and amyloid fibril-free formation of soluble SDS-resistant oligomers ("oligomerization'') by hydrophobic interaction is an in vitro model thought to propagate beta-amyloid (Abeta) deposition, accumulation, and incur neurotoxicity and synaptotoxicity in Alzheimer's disease (AD), and other amyloid-associated neurodegenerative diseases. However, Abeta is a high-affinity metalloprotein that aggregates in the presence of biometals ( zinc, copper, and iron), and neocortical Abeta deposition is abolished by genetic ablation of synaptic zinc in transgenic mice. We now present in vitro evidence that trace ( less than or equal to 0.8 muM) levels of zinc, copper, and iron, present as common contaminants of laboratory buffers and culture media, are the actual initiators of the classic Abeta1 - 42-mediated seeding process and Abeta oligomerization. Replicating the experimental conditions of earlier workers, we found that the in vitro precipitation and amyloidosis of Abeta1 - 40 (20 muM) initiated by Abeta1 - 42 ( 2 muM) were abolished by chelation of trace metal contaminants. Further, metal chelation attenuated formation of soluble Abeta oligomers from a cell-free culture medium. These data suggest that protein self-assembly and oligomerization are not spontaneous in this system as previously thought, and that there may be an obligatory role for metal ions in initiating Abeta amyloidosis and oligomerization. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Mass Gen Inst Neurodgenerat Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, MassGen Inst Neurodgenerat Dis, Boston, MA 02114 USA. RP Huang, XD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM huangx@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [5F32AG05782, 5R01AG12685]; NIMH NIH HHS [5K01MH02001] NR 52 TC 146 Z9 149 U1 0 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD DEC PY 2004 VL 9 IS 8 BP 954 EP 960 DI 10.1007/s00775-004-0602-8 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 875HR UT WOS:000225411400004 PM 15578276 ER PT J AU Ledoux, WR Meaney, DF Hillstrom, HJ AF Ledoux, WR Meaney, DF Hillstrom, HJ TI A quasi-linear, viscoelastic, structural model of the plantar soft tissue with frequency-sensitive damping properties SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE foot; biomechanics; heel; metatarsals ID HUMAN HEEL PAD; MECHANICAL-PROPERTIES; FAT PAD; RESPONSES; FOOT; COMPRESSION; THICKNESS; BEHAVIOR; LIGAMENT; SOLE AB Little is known about the structural properties of plantar soft-tissue areas other than the heel; nor is it known whether the structural properties vary depending on location. Furthermore, although the quasi-linear viscoelastic (QLV) theory, has been used to model many soft-tissue types, it has not been employed to model the plantar soft tissue. The structural properties of the plantar soft tissue were quantified via stress relaxation experiments at seven regions (subcolcaneal, five submetatarsal, and subhallucal) across eight codaveric feet. The cadaveric feet were 36.9+/-17.4 (mean+/-S.D.) Years of age, all free front vascular diseases and orthopedics disorders. All tests were performed at a constant environmental temperature of 35degreesC. Stress relaxation experiments it ere performed: different loads were employed for different areas based on normative gait data. A modification of the relaxation spectrum employed within the QLV theory allowed for the inclusion of frequency-sensitive relaxation properties in addition to nonlinear elastic behavior The tissue demonstrated frequency-dependent damping properties that made the QLV theory ill suited to model the relaxation. There was a significant difference between the elastic structural properties (A) of the subcalcaneal tissue and all other areas (p=0.004), and a trend (p=0.067) for the fifth submetatarsal to have less viscous damping (cl) than the subhallucal, or first. second, or third submetatarsal areas. Thus, the data demonstrate that the structural properties of the foot can van: across regions, but careful consideration must be given to the applied loads and the manner in which the loads were applied. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Temple Univ, Sch Med, Gait Study Ctr, Philadelphia, PA 19107 USA. RP Ledoux, WR (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 29 TC 14 Z9 14 U1 1 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD DEC PY 2004 VL 126 IS 6 BP 831 EP 837 DI 10.1115/1.1824133 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 901XD UT WOS:000227314700017 PM 15796342 ER PT J AU Shimizu, N Dean, T Khatri, A Gardella, TJ AF Shimizu, N Dean, T Khatri, A Gardella, TJ TI Amino-terminal parathyroid hormone fragment analogs containing alpha,alpha-di-alkyl amino acids at positions 1 and 3 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PHOTOAFFINITY CROSS-LINKING; (PTH)/PTH-RELATED PROTEIN-RECEPTOR; PTH/PTHRP RECEPTOR; PTH-1 RECEPTOR; MOLECULAR CHARACTERIZATION; JUXTAMEMBRANE REGION; MUTATIONAL ANALYSIS; LIGAND INTERACTION; BINDING DOMAIN; AGONIST AB To define and minimize the N-terminal PTH pharmacophore, the effects of introducing different conformationally constraining di-alkyl amino acids at positions 1 and 3 of PTH(1-14) analogs were studied. Improvements in PTH receptor-binding affinity and signaling potency were found, although some substitutions resulted in partial agonism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Biopolymer Core Facil, Boston, MA 02115 USA. RP Gardella, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM Gardella@helix.MGH.Harvard.edu FU NIDDK NIH HHS [DK-11794] NR 44 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2004 VL 19 IS 12 BP 2078 EP 2086 DI 10.1359/JBMR.040914 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 874HO UT WOS:000225341700019 PM 15537452 ER PT J AU Hoffman, M Ferri, J Sison, C Roter, D Schapira, L Baile, W AF Hoffman, M Ferri, J Sison, C Roter, D Schapira, L Baile, W TI Teaching communication skills: An AACE survey of oncology training programs SO JOURNAL OF CANCER EDUCATION LA English DT Article ID CANCER-PATIENTS; BAD-NEWS; FELLOWS; HEALTH; CARE AB Background. The extent of communication skills training (CST) in American oncology fellowship programs is unknown. Methods. A survey was sent to program directors of medical oncology, radiation oncology, gynecologic oncology, and surgical oncology training programs regarding (1) the presence and method(s) of CST in their programs, (2) their attitude about mandatory CST, and (3) their attitude about a mandatory assessment of communication skills competence as a prerequisite for specialty certification. Results. Only a third of programs contained some form of CST Surgical oncology programs were particularly tacking. Lack of faculty time was cited as the major barrier to implementing CST A majority of program directors support mandatory CST but not a core competence requirement for certification. Conclusions. There is a current deficiency in CST in American oncology fellowship training. Given the importance of communication skills in the provision of high-quality cancer care, initiatives to address this deficiency are a priority. C1 Albert Einstein Coll Med, Div Hematol Oncol, Long Isl Jewish Med Ctr, New Hyde Pk, NY 11040 USA. N Shore Long Isl Jewish Res Inst, Biostat Unit, Manhasset, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. MD Anderson Canc Ctr, Sect Psychiat, Dept Neurooncol, Houston, TX USA. RP Hoffman, M (reprint author), Albert Einstein Coll Med, Div Hematol Oncol, Long Isl Jewish Med Ctr, 270-05 76th Ave, New Hyde Pk, NY 11040 USA. EM mhoffma@lij.edu RI Roter, Debra/N-8830-2014 NR 18 TC 20 Z9 20 U1 0 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2004 VL 19 IS 4 BP 220 EP 224 DI 10.1207/s15430154jce1904_8 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 899MK UT WOS:000227148300005 PM 15725639 ER PT J AU Mann, DL AF Mann, DL TI Basic mechanisms of left ventricular remodeling: The contribution of wall stress SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE left ventricular remodeling; stretch; signal transduction; heart failure ID CONGESTIVE-HEART-FAILURE; SIGNAL-TRANSDUCTION PATHWAYS; BETA-ADRENERGIC-BLOCKADE; ACTIVATED ION CHANNELS; GTP-BINDING PROTEINS; CARDIAC MYOCYTES; DILATED CARDIOMYOPATHY; STRETCH; HYPERTROPHY; DISEASE AB Heart failure may be viewed as a progressive disorder that is impelled, at least in part, by progressive left ventricular (LV) remodeling. In the present discussion we will review the role of LV remodeling in the pathogenesis of heart failure, with a focus on the contribution that increased wall stress plays in the development and progression of LV remodeling. The clinical implication of this review is that existing neurohormonal strategies may not completely prevent disease progression in the failing heart, and that adjunctive strategies that are designed to specifically prevent or attenuate LV remodeling may play an important role in the clinical treatment of heart failure. C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, 6565 Fannin,MS 524, Houston, TX 77030 USA. FU NHLBI NIH HHS [R01 HL58081-01, P50 HL-O6H] NR 46 TC 24 Z9 25 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD DEC PY 2004 VL 10 IS 6 SU S BP S202 EP S206 DI 10.1016/j.cardfail.2004.09.008 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 885FL UT WOS:000226142400003 PM 15803551 ER PT J AU Yarbrough, WM Mukherjee, R Squires, CE Reese, ES Leiser, JS Stroud, RE Sample, JA Hendrick, JW Mingoia, JT McLean, JE Hardin, AE Dowdy, KB Spinale, FG AF Yarbrough, WM Mukherjee, R Squires, CE Reese, ES Leiser, JS Stroud, RE Sample, JA Hendrick, JW Mingoia, JT McLean, JE Hardin, AE Dowdy, KB Spinale, FG TI Caspase inhibition attenuates contractile dysfunction following cardioplegic arrest and Rewarming in the setting of left ventricular failure SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE caspase; myocyte; LV failure; contractility ID MYOCARDIAL INFARCT SIZE; POTASSIUM CARDIOPLEGIA; RECEPTOR BLOCKADE; HEART-FAILURE; IN-VIVO; ISCHEMIA; ACTIVATION; APOPTOSIS; RECOVERY; TARGET AB Hyperkalemic cardioplegic arrest (HCA) and rewarming evokes postoperative myocyte contractile dysfunction, a phenomenon of particular importance in settings of preexisting left ventricular (LV) failure. Caspases are intracellular proteolytic enzymes recently demonstrated to degrade myocardial contractile proteins. This study tested the hypothesis that myocyte contractile dysfunction induced by HCA could be ameliorated with caspase inhibition in the setting of compromised myocardial function. LV myocytes were isolated from control pigs (n = 9, 30 kg) or pigs with LV failure induced by rapid pacing (n = 6, 240 bpm for 21 days) and were randomized to the following: (1) normothermia (2003 myocytes), incubation in cell culture medium for 2 hours at 37degreesC; (2) HCA only (506 myocytes), incubation for 2 hours in hypothermic HCA solution (4degreesC, 24 mEq K+); or (3) HCA + z-VAD, incubation in hypothermic HCA solution supplemented with 10 muM of the caspase inhibitor z-VAD (z-Val-Ala-Asp-fluoromethyl-ketone, 415 myocytes). Inotropic responsiveness was examined using beta-adrenergic stimulation (25 nM isoproterenol). Ambient normothermic myocyte shortening velocity (mum/s) was reduced with LV failure compared with control values (54 +/- 2 versus 75 +/- 2, respectively, P < 0.05). Following HCA, shortening velocity decreased in the LV failure and control groups (27 +/- 5 and 45 +/- 3, P < 0.05). Institution of z-VAD increased myocyte shortening velocity following HCA in both the LV failure and control groups (49 +/- 5 and 65 +/- 5, P < 0.05). Moreover, HCA supplementation with z-VAD increased beta-adrenergic responsiveness in both groups compared with HCA-only values. This study provides proof of concept that caspase activity contributes to myocyte contractile dysfunction following simulated HCA. Pharmacologic caspase inhibition may hold particular relevance in the execution of cardiac surgical procedures requiring HCA in the context of preexisting LV failure. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph Johnson Vet Assoc Med Ctr, Charleston, SC 29425 USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,770 MUSC Complex,Suite 62, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [HL-07260, HL-48788, HL-56603] NR 24 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD DEC PY 2004 VL 44 IS 6 BP 645 EP 650 DI 10.1097/00005344-200412000-00004 PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 877HR UT WOS:000225559200004 PM 15550782 ER PT J AU Singh, BN AF Singh, BN TI Pursuit of sinus rhythm in patients with atrial fibrillation: Is the effort worth it? SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material ID QUALITY-OF-LIFE; CARDIOVERSION; PREVENTION; IMPAIRMENT; MANAGEMENT; DISEASE; RISK C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Singh, BN (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Cardiol 111E, Los Angeles, CA 90073 USA. EM bsingh@ucla.edu NR 17 TC 2 Z9 2 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2004 VL 9 IS 4 BP 219 EP 221 DI 10.1177/107424840400900401 PG 3 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 890EY UT WOS:000226495700001 PM 15678240 ER PT J AU Satwani, S Dec, GW Narula, J AF Satwani, S Dec, GW Narula, J TI beta-adrenergic blockers in heart failure: Review of mechanisms of action and clinical outcomes SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE beta-adrenergic pathway; beta-blocker therapy; heart failure ID LEFT-VENTRICULAR FUNCTION; MYOCARDIAL-INFARCTION; CARVEDILOL; METOPROLOL; BLOCKADE; TRIAL; SURVIVAL; COMET; GUIDELINES; MORTALITY AB Better understanding of the pathophysiology of heart failure has shifted the treatment of heart failure away from enhancing myocardial contractility to a new paradigm that targets the root cause of disease progression by blocking the adverse effects of excessive neurohormonal activation. beta-Adrenergic receptor-blockers have emerged as a cornerstone in the management of symptomatic heart failure. This article reviews the normal functioning of the beta-adrenergic pathway, the consequences of hyperadrenergism on this crucial signaling pathway, and the mechanisms by which chronic beta-blocker therapy reverses these abnormalities. The clinical evidence from controlled trials of the efficacy of beta-blockers in treating heart failure is summarized. Finally, the concomitant use of beta-blockers and positive inotropic agents in advanced heart failure is discussed. C1 Massachusetts Gen Hosp, Heart Failure & Transplant Ctr, Boston, MA 02114 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Calif Irvine, Irvine, CA USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Heart Failure & Transplant Ctr, Bigelow 840, Boston, MA 02114 USA. EM gdec@partners.org NR 32 TC 20 Z9 21 U1 1 U2 2 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1074-2484 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2004 VL 9 IS 4 BP 243 EP 255 DI 10.1177/107424840400900404 PG 13 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 890EY UT WOS:000226495700004 PM 15678243 ER PT J AU Ebrahimi, R Saleh, JR Toggart, EJ Hayatdavoudi, B Wolf, CJ Wadhani, NN Shah, AP AF Ebrahimi, R Saleh, JR Toggart, EJ Hayatdavoudi, B Wolf, CJ Wadhani, NN Shah, AP TI Lipid-lowering therapy in patients with peripheral arterial disease SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE peripheral arterial disease; hypocholesterolemic drugs; HMG-CoA inhibitors; lipid therapy ID ANKLE-BRACHIAL INDEX; FEMORAL ATHEROSCLEROSIS; VASCULAR-DISEASE; INTERMITTENT CLAUDICATION; CHOLESTEROL REDUCTION; LEG SYMPTOMS; TRIAL; PREDICTOR; EVENTS; PROGRESSION AB Peripheral arterial disease (PAD) is a prevalent, chronic, and progressive atherosclerotic disease process involving the conduit vessels of the extremities. Most patients who present with objective signs of PAD are asymptomatic. These patients are at an increased risk of dying from cardiovascular events. Lipid management is the mainstay of risk-factor modification for patients with cardiovascular disease. Some evidence suggests that hypocholesterolemic drugs may halt the progression of atherosclerotic peripheral vascular disease. More recently, treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors have demonstrated improved function in patients with symptomatic peripheral vascular disease. This paper reviews the role of lipid therapy in patients with peripheral arterial disease with focus on functional improvement and symptomatic relief based on the available data. C1 Greater Los Angeles VA Med Ctr, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Ebrahimi, R (reprint author), Greater Los Angeles VA Med Ctr, Div Cardiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM rami.ebrahimi@med.va.gov NR 35 TC 4 Z9 4 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1074-2484 EI 1940-4034 J9 J CARDIOVASC PHARM T JI J. Cardiovasc. Pharmacol. Ther. PD DEC PY 2004 VL 9 IS 4 BP 271 EP 277 DI 10.1177/107424840400900407 PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 890EY UT WOS:000226495700007 PM 15678246 ER PT J AU Huang, Y Corbley, MJ Tang, ZQ Yang, L Peng, Y Zhang, ZY Tong, TJ AF Huang, Y Corbley, MJ Tang, ZQ Yang, L Peng, Y Zhang, ZY Tong, TJ TI Down-regulation of p21(WAF1) promotes apoptosis in senescent human fibroblasts: Involvement of retinoblastoma protein phosphorylation and delay of cellular aging SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID GROWTH-FACTOR; IN-VIVO; EXPRESSION; CELLS; INHIBITOR; DEATH; GENE; P21; CYCLE; P53 AB It has been suggested that genes which exercise checkpoint control during cell cycle traverse are equally important to the process of apoptotic cell death. In this study, we show that the key cell cycle regulatory gene p21(WAF1) is also involved in the execution of apoptosis. p21(WAF1) expression was down-regulated during NaBu-induced apoptosis of senescent normal diploid human 2BS fibroblasts. Conversely, when p21(WAF1) expression was actively suppressed in 2BS cells by a stably transfected antisense p21(WAF1) construct, apoptosis was accelerated and senescence was delayed, as shown by several markers of cell aging. Downregulation of p21(WAF1) by antisense caused an increase in the phosphorylation and inactivation of pRb. Phosphorylation of pRb was further enhanced upon induction of apoptosis by NaBu. Our results suggest that p21(WAF1), acting through the phosphorylation of pRb, regulates whether 2BS cells cease to proliferate and become senescent but resistant to apoptosis, or whether they accelerate proliferation while becoming more susceptible to apoptotic stimuli. (C) 2004 Wiley-Liss, Inc. C1 Peking Univ, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100083, Peoples R China. Biogen Corp, Dept Mol & Cell Biol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Zhang, ZY (reprint author), Peking Univ, Dept Biochem & Mol Biol, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100083, Peoples R China. EM ttj@bjmu.edu.cn NR 42 TC 9 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 2004 VL 201 IS 3 BP 483 EP 491 DI 10.1002/jcp.20125 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 867WU UT WOS:000224874300017 PM 15389598 ER PT J AU Swanson, JM Biederman, J Boellner, SW Earl, C Lopez, FA AF Swanson, JM Biederman, J Boellner, SW Earl, C Lopez, FA TI Modafinil as therapy for ADHD in children: An 8-week, open-label study SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH C1 Univ Calif Irvine, Irvine, CA USA. Massachusetts Gen Hosp, Cambridge, MA USA. Neurol & Clin Study Ctr, Little Rock, AR USA. Cephalon Inc, W Chester, PA USA. Childrens Dev Ctr PA, Maitland, FL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2004 VL 14 IS 4 BP 512 EP 513 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 891PD UT WOS:000226592100011 ER PT J AU Spencer, TJ Faraone, SV Morgan, JA Mays, DA Michaels, MA Tulloch, S AF Spencer, TJ Faraone, SV Morgan, JA Mays, DA Michaels, MA Tulloch, S TI A cohort analysis of measured growth parameters in children with attention-deficit hyperactivity disorder receiving mixed amphetamine salts (MAS XR) for 24 months\ SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Shire Pharmaceut Dev Inc, Rockville, MD USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2004 VL 14 IS 4 BP 513 EP 513 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 891PD UT WOS:000226592100012 ER PT J AU Spencer, T McGough, J Muniz, R Pestreich, L Kim, S Jiang, H Agoropoulou, C Etropolski, M AF Spencer, T McGough, J Muniz, R Pestreich, L Kim, S Jiang, H Agoropoulou, C Etropolski, M CA Adult ADHD Study Grp TI Efficacy of dexmethylphenidate extended-release capsules in adults with attentiondeficit/hyperactivity disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Novartis Pharmaceut, E Hanover, NJ USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2004 VL 14 IS 4 BP 515 EP 516 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 891PD UT WOS:000226592100016 ER PT J AU Kogan, JN Bauer, MS Wisniewski, SS Marangell, L Thase, ME Sachs, G AF Kogan, JN Bauer, MS Wisniewski, SS Marangell, L Thase, ME Sachs, G TI Paroxetine and suicidality in a high-risk population SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. Providence VA, Providence, RI USA. Univ Pittsburgh, Pittsburgh, PA USA. Baylor Coll Med, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2004 VL 14 IS 4 BP 518 EP 518 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 891PD UT WOS:000226592100020 ER PT J AU Viguera, AC Cohen, LS Reminick, AM Bender, R LeBlanc, GA Hennen, J AF Viguera, AC Cohen, LS Reminick, AM Bender, R LeBlanc, GA Hennen, J TI Anticonvulsants in pregnancy and lactation: Differences in attitudes and practice patterns among neurologists and psychiatrists SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH C1 Massachusetts Gen Hosp, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2004 VL 14 IS 4 BP 529 EP 529 PG 1 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 891PD UT WOS:000226592100039 ER PT J AU Mulder, JE Bilezikian, JP AF Mulder, JE Bilezikian, JP TI Bone density in survivors of childhood cancer SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE peakbone mass; childhood cancer survivors; osteoporosis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; ESTROGEN REPLACEMENT THERAPY; CONGENITAL AROMATASE DEFICIENCY; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; YOUNG-ADULT SURVIVORS; LONG-TERM SURVIVORS; MINERAL DENSITY; GROWTH-HORMONE AB Advances in combination chemotherapy, radiation therapy, surgery, and bone marrow transplantation have resulted in markedly improved survival rates for many children with cancer. Advancements in therapy, however, have led to new concerns, namely long-term consequences of effective treatments. Young adult and adult survivors of childhood cancer are at risk for a number of disorders related to therapy. Specifically., the young adult who has survived cancer, attendant treatments, and their complications is at risk for factors that can lead to suboptimal acquisition of peak bone mass. These factors include chronic illness, nutritional deficiencies, limited physical activity, and treatment with glucocorticoids, multiagent chemotherapy, and radiation. The long-term adverse effects of these therapies on endocrine systems, especially sex steroid and growth hormone deficiencies, are additional risk factors for some patients. After a brief review of the processes associated with acquisition of peak bone mass in the young adult, this article examines the impact of cancer and cancer therapy on bone mineral density in survivors of childhood cancer. C1 Coll Phys & Surg, Dept Med, New York, NY USA. Coll Phys & Surg, Dept Pharmacol, New York, NY USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mulder, JE (reprint author), Brigham & Womens Hosp, Div Endocrine, 221 Longview Ave,RFB-2, Boston, MA 02115 USA. EM JMULDER@partners.org NR 92 TC 8 Z9 9 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD WIN PY 2004 VL 7 IS 4 BP 432 EP 442 DI 10.1385/JCD:7:4:432 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 890FL UT WOS:000226497000013 PM 15618605 ER PT J AU Laspa, E Bastepe, M Juppner, H Tsatsoulis, A AF Laspa, E Bastepe, M Juppner, H Tsatsoulis, A TI Phenotypic and molecular genetic aspects of pseudohypoparathyroidism type Ib in a Greek kindred: Evidence for enhanced uric acid excretion due to parathyroid hormone resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; ALBRIGHT HEREDITARY OSTEODYSTROPHY; ALPHA-SUBUNIT G(S)ALPHA; PRIMARY HYPERPARATHYROIDISM; MULTIPLE HORMONES; VITAMIN-D; URATE; MECHANISMS; MUTATIONS; DISEASE AB The predominant feature of pseudohypoparathyroidism (PHP) is renal resistance to PTH. Pseudohypoparathyroidism type Ia (PHP-Ia) is caused by maternally inherited heterozygous mutations in the GNAS exons encoding the alpha-subunit of the stimulatory G protein (G(s)alpha). Besides PTH resistance, PHP-Ia patients have Albright's hereditary osteodystrophy and often display resistance to additional hormones. Patients with PHP-Ib lack features of Albright's hereditary osteodystrophy, and PTH resistance is associated with loss of methylation at the maternal GNAS exon A/B. Most individuals with the autosomal dominant form of PHP-Ib have a 3-kb microdeletion within STX16 approximately 220 kb upstream of exon A/B. Here we report on the clinical and genetic aspects of a Greek PHP-Ib kindred with four affected members and three obligate carriers, who had the 3-kb deletion within STX16. Symptomatic hypocalcemia was present only in the proband, but PTH was elevated in all members who had inherited the 3-kb deletion maternally. In all affected family members, urinary phosphate excretion was normal, but 1,25-dihydroxyvitamin D levels were diminished. These findings confirm previous data regarding patient to patient variation in disease severity for autosomal dominant PHP-Ib. Furthermore, affected individuals displayed hypouricemia with increased fractional excretion of uric acid, suggesting possible involvement of PTH in the renal handling of this metabolite. C1 Univ Ioannina, Dept Med, Div Endocrinol, GR-45110 Ioannina, Greece. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. MassGeneral Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Tsatsoulis, A (reprint author), Univ Ioannina, Dept Med, Div Endocrinol, GR-45110 Ioannina, Greece. EM atsatsou@cc.uoi.gr NR 40 TC 19 Z9 21 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2004 VL 89 IS 12 BP 5942 EP 5947 DI 10.1210/jc.2004-0249 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 876KJ UT WOS:000225495400011 PM 15579741 ER PT J AU Wolf, M Hubel, CA Lam, C Sampson, M Ecker, JL Ness, RB Rajakumar, A Daftary, A Shakir, ASM Seely, EW Roberts, JM Sukhatme, VP Karumanchi, SA Thadhani, R AF Wolf, M Hubel, CA Lam, C Sampson, M Ecker, JL Ness, RB Rajakumar, A Daftary, A Shakir, ASM Seely, EW Roberts, JM Sukhatme, VP Karumanchi, SA Thadhani, R TI Preeclampsia and future cardiovascular disease: Potential role of altered angiogenesis and insulin resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PREGNANCY COMPLICATIONS; TYROSINE KINASE-1; NAD(P)H OXIDASE; MESSENGER-RNA; RECEPTOR; RISK; HYPERTENSION; EXPRESSION; PLASMA AB Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Brigham & Womens Hosp, Endocrinol Diabet & Hypertens Div, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Obstet & Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU NCRR NIH HHS [M01RR00056, M01RR01066, RR071376]; NHLBI NIH HHS [HL64144]; NICHD NIH HHS [HD30367, HD39223]; NIDDK NIH HHS [DK02825, DK64255] NR 36 TC 123 Z9 129 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 2004 VL 89 IS 12 BP 6239 EP 6243 DI 10.1210/jc.2004-0548 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 876KJ UT WOS:000225495400053 PM 15579783 ER PT J AU Collins, TC Suarez-Almazor, M Petersen, NJ O'Malley, KJ AF Collins, TC Suarez-Almazor, M Petersen, NJ O'Malley, KJ TI A Spanish translation of the Walking Impairment Questionnaire was validated for patients with peripheral arterial disease SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE peripheral arterial disease; Walking Impairment; Hispanic Americans; questionnaires ID IQOLA PROJECT APPROACH; SCALING ASSUMPTIONS; GENERAL-POPULATION; PHYSICAL-ACTIVITY; DATA QUALITY; RELIABILITY; PREVALENCE; WOMEN AB Objectives: Walking impairment is a common manifestation of peripheral arterial disease (PAD). In this study we present evidence for the validity of our Spanish translation of the Walking Impairment Questionnaire (WIQ). Methods: The WIQ was translated into Spanish by our team of researchers. Spanish-speaking patients in the Houston. TX. area completed Spanish versions of the WIQ and the SF-36. Evidence for convergent and discriminant validity of the WIQ was obtained from correlations between the WIQ and other measures. Spanish or English as the primary language defined language-swaking status. Results: Amon- 403 patients, convergent validity evidence was strong for both English- and Spanish-speaking patients. For patients with PAD, the correlation between walking distance and physical functioning was 0.55 (P <.01) for English-speaking patients and 0.85 (P <.01) for Spanish-speaking patients. The correlations of walking impairment with emotional health measures ranged from 0.26 to 0.44 for English-speaking patients (P <.01) and from 0.34 to 0.78 for Spanish-speaking patients. Conclusions: The WIQ scores Correlated well with SF-36 components for both English- and SpaniSh-speaking patients. Our findings, suggested that our translation process did not limit our ability to capture good-quality data. Further research is needed to deteirniine what specific items in the WIQ or the SF-36 questionnaire warrant restructuring to increase their validity for use in diverse populations. (C) 2004 Elsevier Inc. All rights reserved. C1 Baylor Coll Med, Micael E DeBakey VA Med Ctr, Houston, TX 77030 USA. Houston Va Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP Collins, TC (reprint author), Baylor Coll Med, Micael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,152, Houston, TX 77030 USA. EM tcollins@bcm.tmc.edu NR 31 TC 19 Z9 19 U1 11 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 2004 VL 57 IS 12 BP 1305 EP 1315 DI 10.1016/j.jclinepi.2004.03.005 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 885KA UT WOS:000226154300012 PM 15617957 ER PT J AU Weyman, AE Scherrer-Crosbie, M AF Weyman, AE Scherrer-Crosbie, M TI Marfan syndrome and mitral valve prolapse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID TGF-BETA ACTIVATION; PREVALENCE; MUTATIONS; PHENOTYPE; DIAGNOSIS; DISEASE; SURGERY; LOCUS; RISK AB Mitral valve prolapse (MVP), an abnormal displacement into the left atrium of a thickened and redundant mitral valve during systole, is a relatively frequent abnormality in humans and may be associated with serious complications. A recent study implicates fibrillin-1, a component of extracellular matrix microfibrils, in the pathogenesis of a murine model of MVP (see the related article beginning on page 1586). This investigation represents an initial step toward understanding the mechanisms involved in human MVP disease and the development of potential treatments. C1 Massachusetts Gen Hosp, Dept Med, Cardiac Ultrasound Lab, Cardiol Div, Boston, MA 02114 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiac Ultrasound Lab, Cardiol Div, 55 Fruit St, Boston, MA 02114 USA. EM aweyman@partners.org NR 31 TC 21 Z9 23 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2004 VL 114 IS 11 BP 1543 EP 1546 DI 10.1172/JCI200423701 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 876DK UT WOS:000225475900005 PM 15578086 ER PT J AU Burn, AK Fothergill, AW Kirkpatrick, WR Coco, BJ Patterson, TF McCarthy, DI Rinaldi, MG Redding, SW AF Burn, AK Fothergill, AW Kirkpatrick, WR Coco, BJ Patterson, TF McCarthy, DI Rinaldi, MG Redding, SW TI Comparison of antifungal susceptibilities to fluconazole and voriconazole of oral Candida glabrata isolates from head and neck radiation patients SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PATIENTS RECEIVING RADIATION; RESISTANCE; RAVUCONAZOLE; COLONIZATION; INFECTIONS; CANCER; AGENTS AB The antifungal susceptibilities of 79 oral Candida glabrata isolates to fluconazole and voriconazole were compared. The MICs at which 90% of the isolates tested were inhibited were 1 mug of voriconazole/ml and 32 mug of fluconazole/ml. Oral C. glabrata isolates for which the fluconazole MICs are elevated are commonly those for which the voriconazole MICs are elevated, but these increases may be transient for voriconazole, as they are for fluconazole. C1 Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, San Antonio, TX USA. RP Burn, AK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Gen Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM burn@uthscsa.edu NR 16 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 2004 VL 42 IS 12 BP 5846 EP 5848 DI 10.1128/JCM.42.12.5846-5848.2004 PG 3 WC Microbiology SC Microbiology GA 883SK UT WOS:000226035800061 PM 15583322 ER PT J AU Sparano, JA Bernardo, P Stephenson, P Gradishar, WJ Ingle, JN Zacker, S Davidson, NE AF Sparano, JA Bernardo, P Stephenson, P Gradishar, WJ Ingle, JN Zacker, S Davidson, NE TI Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group Trial E2196 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FL SP Amer Soc Clin Oncol ID MATRIX-METALLOPROTEINASE INHIBITOR; MATRILYSIN EXPRESSION; MAINTENANCE THERAPY; ADULT PERIODONTITIS; PANCREATIC-CANCER; CREVICULAR FLUID; TISSUE INHIBITOR; MMP INHIBITION; POOR-PROGNOSIS; LINE THERAPY AB Purpose To determine whether a matrix metalloproteinase inhibitor improves progression-free survival (PIFS) in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy. Patients and Methods One hundred seventy-nine eligible patients were randomly assigned to receive oral marimastat (10 mg bid; n = 114) or a placebo (n = 65) within 3 to 6 weeks of completing six to eight cycles of first-line doxorubicin- and/or taxane-containing chemotherapy for metastatic disease. Patients were evaluated every 3 months until disease progression. Results When comparing placebo with marimastat, there was no significant difference in PFS (median, 3.1 months v 4.7 months, respectively; hazard ratio, 1.26; 95% Cl, 0.91 to 1.74; P = .16) or overall survival (median, 26.6 months v 24.7 months, respectively; hazard ratio, 1.03; 95% Cl, 0.73 to 1.46; P = .86). Patients treated with marimastat were more likely to develop grade 2 or 3 musculoskeletal toxicity (MST), a known complication of the drug indicative of achieving a biologic effect, compared with patients administered placebo (63% v 22%, respectively; P < .0001). Patients with grade 2 or 3 MST had significantly inferior survival compared with patients who had grade 0 or 1 MST (median, 22.5 months v 28.2 months; P = .04). In addition, patients who had a marimastat plasma concentration of at least 10 ng/mL at month 1 and/or 3 were significantly more likely to have grade 2 to 3 MST (P < .0001). Conclusion Marimastat does not prolong PFS when used after first-line chemotherapy for metastatic breast cancer. Patients with higher marimastat levels exhibited MST, and MST was associated with inferior survival. (C) 2004 by American Society of Clinical Oncology. C1 Albert Einstein Canc Ctr, Montefiore Med Ctr, Weiler Div, Bronx, NY 10461 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ, Baltimore, MD USA. RP Sparano, JA (reprint author), Albert Einstein Canc Ctr, Montefiore Med Ctr, Weiler Div, 1825 Eastchester Rd,2 S,Rm 47-48, Bronx, NY 10461 USA. EM Sparano@jimmy.harvard.edu FU NCI NIH HHS [CA17145, CA13650, CA66636, CA14958, CA23318, CA21115, CA16116] NR 49 TC 108 Z9 115 U1 2 U2 7 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 DEC 1 PY 2004 VL 22 IS 23 BP 4683 EP 4690 DI 10.1200/JCO.2004.08.054 PG 8 WC Oncology SC Oncology GA 886NW UT WOS:000226236600006 PM 15570070 ER PT J AU Carvalho, LH D'Avila, GB Leao, A Haffajee, AD Socransky, SS Feres, M AF Carvalho, LH D'Avila, GB Leao, A Haffajee, AD Socransky, SS Feres, M TI Scaling and root planing, systemic metronidazole and professional plaque removal in the treatment of chronic periodontitis in a Brazilian population - I. Clinical results SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; metronidazole; oral hygiene; periodontal disease; periodontal therapy; professional supragingival plaque removal; scaling and root planing; subgingival plaque; supragingival plaque; treatment ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; HELICOBACTER-PYLORI INFECTION; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ADULT PERIODONTITIS; PORPHYROMONAS-GINGIVALIS; NONSURGICAL TREATMENT; THERAPY; AMOXICILLIN; DISEASE; TETRACYCLINE AB Objective: The current investigation evaluated the clinical effects of scaling and root planing (SRP) alone or in combination with systemic metronidazole and/or repeated professional removal of supragingival plaque in subjects with chronic periodontitis. Methods: Fourty-four adult subjects (mean age: 45+/-6 years) with periodontitis were randomly assigned to four treatment groups; a control (C, n=10) that received SRP and placebo and three test groups treated as follows: Test 1 (T1) (n=12) received SRP and metronidazole (400 mg t.i.d., M) for 10 days; Test 2 (T2) (n=12) received SRP, weekly professional supragingival plaque removal for three months (professional cleaning (PC)) and placebo; and Test 3 (T3) (n=10) received SRP, M and PC. Pocket depth (PD), attachment level (AL), bleeding on probing (BOP) and presence of visible plaque and suppuration were measured at six sites per tooth at baseline and at 90 days post-therapy. Significance of differences over time was determined using the Wilcoxon test, and among groups using ANCOVA. Results: A reduction in full-mouth mean clinical parameters was observed at 90 days after all therapies. Sites with baseline PD<4 mm showed an increase in mean PD in the control group and in mean AL in all treatment groups. Sites with baseline PD of 4-6 mm in subjects who received PC as part of therapy (T2, T3) showed a marked reduction in PD, AL and in the % of sites with BOP. Subjects who received metronidazole (T1 and T3) showed the best clinical response at sites with an initial PD of >6 mm. The major clinical benefit occurred when the combination of SRP, M and PC was used. Group T3 showed the least attachment loss in initially shallow pockets. This group also exhibited the greatest reduction in the % of sites with BOP and suppuration as well as in mean PD and AL at sites with baseline PD>4 mm. Conclusion: The data suggest a significant clinical benefit in combining SRP, systemic metronidazole and weekly professional supragingival plaque removal for the treatment of chronic periodontitis. C1 Univ Fed Rio de Janeiro, Dept Periodontol, BR-21941 Rio De Janeiro, Brazil. Forsyth Inst, Dept Periodontol, Boston, MA USA. EM mferes@ung.br RI Feres, Magda/H-7964-2012 NR 57 TC 28 Z9 28 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 2004 VL 31 IS 12 BP 1070 EP 1076 DI 10.1111/j.1600-051X.2004.00605.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 873FB UT WOS:000225264200006 PM 15560807 ER PT J AU Misra, M Papakostas, GI Klibanski, A AF Misra, M Papakostas, GI Klibanski, A TI Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID ANTIPSYCHOTIC-INDUCED HYPERPROLACTINEMIA; RISPERIDONE-INDUCED HYPERPROLACTINEMIA; MAJOR DEPRESSIVE DISORDER; HEALTHY MALE-SUBJECTS; MINERAL DENSITY; LONG-TERM; SERUM PROLACTIN; SCHIZOPHRENIC-PATIENTS; ATYPICAL ANTIPSYCHOTICS; PLASMA-PROLACTIN AB Objective: Osteoporosis occurs in common psychiatric conditions and causes significant morbidity. Many neuroleptic medications can cause hyperprolactinemia, which can then potentially be associated with bone loss. Few reviews have thus far addressed this issue. We have consolidated information from studies that examined effects of psychiatric conditions and their treatment on bone metabolism. Data Sources: We searched PubMed for original articles and reviews published between 1976 and 2004 that described changes in bone metabolism in psychiatric disorders and examined prolactin elevations with neuroleptic medications. Keywords used were major depressive disorder, bipolar disorder, schizophrenia, bone density, bone metabolism, hyperprolactinemia, typical antipsychotics, and atypical antipsychotics. Study Selection and Data Extraction: 160 articles published in peer-reviewed journals were identified and are summarized, with greater emphasis given to data from larger, controlled studies. Data Synthesis: Schizophrenia and major mood disorders are often associated with perturbations in bone metabolism related to factors including nutritional alterations, smoking, and hypogonadotropic hypogonadism, with or without medication-induced hyperprolactinemia. Polydipsia can contribute to bone loss in schizophrenia, whereas hypercortisolemia is often associated with low bone density in depression. Lithium in bipolar disorder and thyroid-stimulating hormone-suppressive doses of L-thyroxine have a negative impact on bone health. Mood stabilizers such as carbamazepine and valproate can also affect bone density. Hyperprolactinemia may lead to bone loss only if associated with untreated amenorrhea in women or testosterone deficiency in men. Some atypical neuroleptics, by causing lesser elevations in prolactin, may therefore have a less marked impact on bone than typical neuroleptics. Conclusions: Because significant morbidity is associated with low bone density and many psychiatric conditions may have a negative impact on bone metabolism, bone density evaluation should be considered an integral component of chronic medical care of these disorders, and risk factors should be identified and addressed. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL 457, Boston, MA 02114 USA. EM aklibanski@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NCRR NIH HHS [K23 RR018851]; NIDDK NIH HHS [DK 062249] NR 160 TC 80 Z9 86 U1 1 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2004 VL 65 IS 12 BP 1607 EP 1618 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 884HG UT WOS:000226074800005 PM 15641865 ER PT J AU Hennen, J Perlis, RH Sachs, G Tohen, M Baldessarini, RJ AF Hennen, J Perlis, RH Sachs, G Tohen, M Baldessarini, RJ TI Weight gain during treatment of bipolar I patients with olanzapine SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ACUTE MANIA; DIVALPROEX SODIUM; DIABETES-MELLITUS; DISORDER; MORTALITY; PLACEBO; SCHIZOPHRENIA; EFFICACY; SCALE; RELIABILITY AB Background: Body weight increase during long-term treatment with olanzapine in schizophrenia patients is well documented, but weight gain and its association with other medical measures are less well evaluated in bipolar disorder patients. Method: We analyzed data from a 3-week, randomized, placebo-controlled trial of olanzapine for acute mania in DSM-IV bipolar I patients, followed by open continuation treatment with olanzapine up to a year. We examined factors associated with increased body mass index (BMI), including ratings of clinical change and selected physiologic measures. Results: Among 113 subjects treated with olanzapine for a mean +/- SD of 28.6 +/- 19.9 weeks, BMI increased from a baseline mean of 28.8 +/- 6.2 kg/m(2), by 7.9 +/- 10.8% (p < .001), into the obese range (31.0 +/- 6.1 kg/m(2)). Initial BMI change (first 3 weeks of drug exposure) predicted final BMI increases (Spearman rank correlation r(s) = 0.32, p < .001). History of longer illness (p = .006) and lifetime substance abuse (p = .02) were associated with below-median BMI increases. BMI increased much more among 40 subjects achieving symptomatic recovery than in the 73 who did not (by 11.9 +/- 13.2% vs. 5.3 +/- 7.7%; p = .004), with correspondingly longer olanzapine exposure (44.7 +/- 11.8 vs. 19.7 +/- 17.7 weeks; p < .001) at similar doses. On average, serum cholesterol increased 4.8 times more (17.5% vs. 3.6%) and endpoint cholesterol levels were newly 240 mg/dL or greater 3.6 (95% CI = 1.5 to 8.0) times more frequently in subjects with above-median BMI gain, who also experienced significantly larger increases in systolic and diastolic blood pressure, pulse rates, and nonfasting serum glucose than low-BMI-gain subjects. Conclusions: Weight gain associated with long-term olanzapine treatment for mania was common, substantial, time-dependent, predicted by initial increases, and temporally associated with significant changes in cardiovascular and metabolic measures in bipolar I patients with prolonged illness and already-high basal BMI. An association of weight gain with favorable clinical response probably reflects longer olanzapine treatment. C1 McLean Hosp, Biostat Lab, Bipolar & Psychot Disorders Program, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Bipolar Disorder Unit, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Hennen, J (reprint author), McLean Hosp, Biostat Lab, Bipolar & Psychot Disorders Program, 115 Mill St,Adm Bldg, Belmont, MA 02478 USA. EM jhennen@mclean.org NR 32 TC 42 Z9 43 U1 3 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 2004 VL 65 IS 12 BP 1679 EP 1687 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 884HG UT WOS:000226074800014 PM 15641874 ER PT J AU Alpert, JE Papakostas, G Mischoulon, D Worthington, JJ Petersen, T Mahal, Y Burns, A Bottiglieri, T Nierenberg, AA Fava, M AF Alpert, JE Papakostas, G Mischoulon, D Worthington, JJ Petersen, T Mahal, Y Burns, A Bottiglieri, T Nierenberg, AA Fava, M TI S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder - An open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ADENOSYLMETHIONINE; HOMOCYSTEINE; QUESTIONNAIRE; EFFICACY; PLASMA; SCALE AB Background: The purpose of this open trial was to evaluate the safety, tolerability, and efficacy of oral S-adenosyl-L-methionine as an antidepressant adjunct among partial and nonresponders to serotonin reuptake inhibitors or venlafaxine. Method: Thirty antidepressant-treated adult outpatients with persisting major depressive disorder received 800 to 1600 mg of S-adenoSyl-L-methionine tosylate over a 6-week trial. Results: Intent-to-treat analyses based on the Hamilton Depression Rating Scale revealed a response rate of 50% and a remission rate of 43% following augmentation with S-adenosyl-L-methionine. Gastrointestinal symptoms and headaches were the most common side effects. Conclusion: Augmentation of selective serotonin reuptake inhibitors or venlafaxine with S-adenosyl-L-methionine warrants a placebo-controlled trial in resistant depression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. Baylor Inst Metabol Dis, Dallas, TX USA. RP Alpert, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, 50 Staniford St,4th Floor, Boston, MA 02114 USA. EM jalpert@partners.org RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 31 TC 53 Z9 54 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 2004 VL 24 IS 6 BP 661 EP 664 DI 10.1097/01.jcp.0000145339.45794.cd PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 872GA UT WOS:000225194500015 PM 15538131 ER PT J AU Greene, RW Ablon, JS Monuteaux, MC Goring, JC Henin, A Raezer-Blakely, L Edwards, G Markey, J Rabbitt, S AF Greene, RW Ablon, JS Monuteaux, MC Goring, JC Henin, A Raezer-Blakely, L Edwards, G Markey, J Rabbitt, S TI Effectiveness of collaborative problem solving in affectively dysregulated children with oppositional-defiant disorder: Initial findings SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article AB Oppositional-defiant disorder (ODD) refers to a recurrent pattern of negativistic, defiant, disobedient, and hostile behavior toward authority figures. Research has shown that children with ODD and comorbid mood disorders may be at particular risk for long-term adverse outcomes, including conduct disorder. In this study, the authors examined the effectiveness of a cognitive-behavioral model of intervention-called collaborative problem solving (CPS)-in comparison with parent training (PT) in 47 affectively dysregulated children with ODD. Results indicate that CPS produced significant improvements across multiple domains of functioning at posttreatment and at 4-month follow-up. These improvements were in all instances equivalent, and in many instances superior, to the improvements produced by PT. Implications of these findings for further research on and treatment selection in children with ODD are discussed. C1 Massachusetts Gen Hosp, Dept Psychiat, Collaborat Problem Solving Inst, Newton, MA 02458 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Childrens Hosp, Dept Psychol, Boston, MA 02115 USA. Suffolk Univ, Dept Psychol, Boston, MA 02108 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Collaborat Problem Solving Inst, 313 Washington St,Suite 402, Newton, MA 02458 USA. EM greene@helix.mgh.harvard.edu NR 27 TC 40 Z9 40 U1 3 U2 16 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2004 VL 72 IS 6 BP 1157 EP 1164 DI 10.1037/0022-006X.72.6.1157 PG 8 WC Psychology, Clinical SC Psychology GA 880PM UT WOS:000225801700022 PM 15612861 ER PT J AU Bartlett, JD Beniash, E Lee, DH Smith, CE AF Bartlett, JD Beniash, E Lee, DH Smith, CE TI Decreased mineral content in MMP-20 null mouse enamel is prominent during the maturation stage SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamelysin; amelogenin; amelogenesis; FTIR; microhardness ID MECHANICAL-PROPERTIES; EXPRESSION; PROTEIN; MICROSTRUCTURE; AMELOGENESIS; CLONING AB During enamel development, matrix metalloproteinase-20 (MMP-20, enamelysin) is expressed early during the secretory stage as the enamel thickens, and kallikrein-4 (KLK-4, EMSP1) is expressed later during the maturation stage as the enamel hardens. Thus, we investigated whether the physical properties of the secretory/ maturation-stage MMP-20 null enamel were significantly different from those of controls. We demonstrated that although, in relative terms, the weight percent of mature mineral in the MMP-20 null mouse enamel was only 7-16% less than that in controls, overall the enamel mineral was reduced by about 50%, and its hardness was decreased by 37%. Percent mineral content by weight was assessed at 3 different developmental stages. Remarkably, the biggest difference in mineral content between MMP-20 null and controls occurred in the nearly mature enamel, when MMP-20 is normally no longer expressed. This suggests that MMP-20 acts either directly or indirectly to facilitate the removal of maturation-stage enamel proteins. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Montreal, Fac Med Dent, Lab Study Calcified Tissues & Biomat, Montreal, PQ H3C 3J7, Canada. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM jbartlett@forsyth.org RI Testes, Olga/E-8912-2013 FU NIDCR NIH HHS [DE14084, R01 DE014084, DE13237] NR 27 TC 72 Z9 73 U1 0 U2 9 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2004 VL 83 IS 12 BP 909 EP 913 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 894MS UT WOS:000226796600004 PM 15557396 ER PT J AU Hsieh, TJ Fustier, P Wei, CC Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Fantus, IG Hamet, P Chan, JSD AF Hsieh, TJ Fustier, P Wei, CC Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Fantus, IG Hamet, P Chan, JSD TI Reactive oxygen species blockade and action of insulin on expression of angiotensinogen gene in proximal tubular cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; CONVERTING ENZYME-INHIBITION; DEPENDENT DIABETES-MELLITUS; PROTEIN-KINASE PATHWAY; CORONARY HEART-DISEASE; II-INDUCED HYPERTROPHY; RAT-KIDNEY; HIGH GLUCOSE; TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1 AB We reported previously that insulin inhibits the stimulatory effect of high glucose on the expression of angiotensinogen (ANG) gene in both rat immortalized renal proximal tubular cells (IRPTCs) and non-diabetic rat renal proximal tubular cells (RPTCs), but has no effect in diabetic rat RPTCs. In the present study we investigated whether hyperglycaemia-induced resistance to the insulin-induced inhibition of expression of the ANG gene is mediated via the generation of reactive oxygen species (ROS) in RPTCs. Rat IRPTCs were cultured for 2 weeks in high-glucose (25 mM) or normal-glucose (5 mM) medium plus angiotensin II (Ang II) with or without a superoxide scavenger (tiron), or inhibitors of NADPH oxidase (diphenylene iodinium, DPI), Ang II type 1 and 2 receptors (losartan and PD123319), angiotensin-converting enzyme (perindopril), protein kinase C (GF 109203X), or glutamine:fructose-6-phosphate amino-transferase (azaserine). Cellular generation of ROS, and ANG and renin mRNA levels were assessed by lucigenin assay and specific reverse transcriptase-PCR respectively. Phosphorylation of p44/42 mitogen-activated protein kinase (p44/42 MAPK) was evaluated by western blotting. Prolonged exposure of IRPTCs to high concentrations of glucose or Ang II evoked generation of ROS and resistance to the insulin-induced inhibition of expression of the ANG gene and of p44/42 MAPK phosphorylation. Co-incubation of IRPTCs with tiron, DPI losartan, PD123319, perindopril, GF 109203X or azaserine prevented ROS generation, restoring the inhibitory action of insulin on ANG gene expression and on p44/42 MAPK phosphorylation. In conclusion, our studies demonstrate that blockade of both ROS generation and activation of the intrarenal renin-angiotensin system improves the inhibitory action of insulin on ANG gene expression in IRPTCs in conditions of high glucose. C1 Ctr Hosp Univ Montreal CHUM, Hotel Dieu, Res Ctr, Montreal, PQ H2W 1T8, Canada. Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA 02114 USA. Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. RP Chan, JSD (reprint author), Ctr Hosp Univ Montreal CHUM, Hotel Dieu, Res Ctr, 3850 St Urbain St, Montreal, PQ H2W 1T8, Canada. EM john.chan@umontreal.ca FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 71 TC 29 Z9 32 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 2004 VL 183 IS 3 BP 535 EP 550 DI 10.1677/joe.1.05871 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 882OB UT WOS:000225947100011 PM 15590980 ER PT J AU Olin, JW Jang, J Jaff, MR Beckman, JA Rooke, T AF Olin, JW Jang, J Jaff, MR Beckman, JA Rooke, T TI The top 12 advances in vascular medicine SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Review DE vascular medicine; vascular biology; peripheral artery disease; nitric oxide; metabolic syndrome; angiogenesis; sildenafil; cilostazol; low-molecular-weight heparin; clopidogrel; ACE inhibitors; angiotensin-receptor blocking agents; statins ID MOLECULAR-WEIGHT HEPARIN; PERIPHERAL ARTERIAL-DISEASE; ENDOTHELIAL NITRIC-OXIDE; DEEP-VEIN THROMBOSIS; ACTIVATED PROTEIN-C; HIGH-RISK PATIENTS; WRITING GROUP; INTERMITTENT CLAUDICATION; VENOUS THROMBOEMBOLISM; UNFRACTIONATED HEPARIN AB In the past decade, impressive strides have been made in the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic diseases, thanks in large part to the explosive growth in both vascular biology and clinical vascular medicine. We review what we consider to be the top 12 advances in this field: the discovery of nitric oxide, the metabolic syndrome, new thrombophilic disorders, therapeutic angiogenesis, endoluminal treatment of chronic venous disease, and a variety of drugs, including sildenafil, cilostazol, low-molecular-weight heparins, oral direct thrombin inhibitors, clopidogrel, statins, and angiotensin-converting enzyme inhibitors and angiotensin-receptor blocking agents. C1 Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. Mt Sinai Sch Med, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, New York, NY 10029 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Med, Div Cardiovasc Med, Rochester, MN 55905 USA. RP Olin, JW (reprint author), Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA. EM jeffrey.olin@msnyuhealth.org NR 82 TC 3 Z9 3 U1 0 U2 1 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD DEC PY 2004 VL 11 SU 2 BP 21 EP 31 DI 10.1583/04-1362.1 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 888UG UT WOS:000226399100006 ER EF